PMID- 2874066 TI - Periodic acid-Schiff stain as a prognostic indicator in serous and mucinous ovarian tumors. AB - The prognostic significance of periodic acid-Schiff (PAS) stain in 112 serous: 43 benign, 25 borderline and 44 malignant cystadenomas: and in 106 mucinous: 60 benign, 32 borderline and 14 malignant cystadenomas of the ovary were investigated. The amount of positively stained mucin was estimated morphometrically. The outcome of most patients with benign or borderline lesion was good. One patient with benign mucinous cystadenoma died, however, of pseudomyxoma peritonei and another patient with borderline mucinous cystadenoma died of peritoneal carcinosis. Other patients were alive and free of the disease after a follow-up of 1-14 years, or had died of causes unrelated to the ovarian disease. Abundant PAS positive mucin predicted a longer survival both in serous and in mucinous malignant tumors. The 5-year survivals for the serous cystadenocarcinomas with and without PAS positive mucin were 21% and 13%, respectively (not statistically significant). For mucinous cystadenocarcinomas with mucin value over and below the median, the 5-year survival rates were 57% and 14%, respectively (P less than 0.10). High PAS positivity in both serous and mucinous cystadenocarcinomas clearly indicated better prognosis, although statistical significance was not achieved. Thus, further studies are needed for final evaluation of the prognostic significance of the PAS stain in these ovarian tumors. PMID- 2874067 TI - Management of pregnancy-induced hypertension with pindolol--comparative study with methyldopa. AB - Thirty-two consecutive women with pregnancy-induced hypertension of early onset were randomly allocated to treatment with pindolol or methyldopa. There was no difference between the groups in regard to the average time of delivery (36.33 vs. 36.6 weeks) and weight of the newborn (2850 vs. 2870 g). A significant drop in systolic (P less than 0.005) and diastolic (P less than 0.05) blood pressure was observed in the group of patients treated with pindolol as compared with the methyldopa group. In the pindolol group an improvement in renal function was observed as determined by CCT and serum creatinine. There were no side effects from the drugs in the mother or in the newborn. PMID- 2874068 TI - Normal growth of the fetal biparietal diameter in an African population. AB - The fetal biparietal diameter (BPD) was measured by ultrasound during normal pregnancy in 558 Nigerian women. The range of BPD values for each week of pregnancy from 12 weeks until term (713 measurements) was computed from cross sectional data. The data were used to illustrate the variation in weekly growth rate according to fetal maturity and head size. The results revealed a curve similar to those reported from Caucasian populations but with much less flexion in the later weeks of pregnancy. The BPD values per week were also less in this study group. The reasons for these differences are discussed. PMID- 2874069 TI - Craniofacial defects associated with amniotic band syndrome: a case report. AB - A pathological study was made of a female infant with amniotic band syndrome. At birth, the 1450-g female infant was noted to have craniofacial defects such as anencephaly, cleft lip, severe nasal deformity and asymmetric microphthalmia. The fetal membrane was focally adhered to the scalp, and histological examinations revealed that the connecting area of the fetal head to the membrane resembled a serial architecture from keratinized squamous cells to amniotic layer without any inflammatory findings. These observations suggested that the etiology in the present case may be consistent with Torpin's mesodermic band theory. PMID- 2874070 TI - Induction of labor in postterm pregnant women. AB - We have studied the outcome of labor induction in 145 postterm pregnant women in whom gestational age was properly assessed by ultrasound scanning. The induction techniques were adapted to the cervical states of the patients. Seventy-five patients (32 nulliparous and 43 multiparous) with favorable cervical states were successfully induced with intravenous oxytocin. In this group the frequency of Caesarean section was 2%. Seventy patients (45 nulliparous and 25 multiparous) with unripe cervices received 0.5 mg PGE2 in viscous gel intracervically to prime the cervix and to induce labor; 38 (52%) were induced into labor after a single PGE2-gel application whereas 26 (48%) needed labor augmentation with intravenous oxytocin after PGE2-gel obtained cervical ripening. In 6 of the 20 patients the cervix did not ripen and the PGE2-gel application had then to be repeated. The frequency of cesarean sections was 11%. In 5 out of the 145 patients (4%) the fetuses had signs of intrauterine growth retardation (IUGR) as assessed by ultrasound scanning, and postmaturity as verified by pediatric examination at delivery. All these fetuses belonged to nulliparous women with unripe cervices and all had to be delivered instrumentally (3 by cesarean section and 2 by ventouse) indicating the fragility of these children. If postterm pregnancy is complicated by an unfavorable cervical state intracervical application of PGE2 gel seems to be an efficient method to prime the cervix and to induce labor. In most patients an uncomplicated vaginal delivery can be achieved by this procedure. However, nulliparous women with unfavorable cervices and signs of IUGR constitute a high risk group of patients at labor induction. PMID- 2874071 TI - A review of ten years' experience with surgical equipment in international health programs. AB - The Johns Hopkins Program for International Education in Gynecology and Obstetrics (JHPIEGO) began in June of 1973 with financial assistance from the Agency for International Development (AID). The purpose of the organization was to provide training and medical equipment to physicians in developing countries to update their education in reproductive health. JHPIEGO began by offering courses in the United States and shortly thereafter began training at centers in the developing countries themselves. Because of its important contributions to gynecological diagnosis in addition to its use in fertility management, laparoscopic equipment has been a major item in JHPIEGO reproductive health training. This paper details the development and role of laparoscopic training in JHPIEGO's program. Laparoscopic training begins with selection of trainees from appropriate institutions. Training itself begins with a didactic session at Baltimore or an in-country center. Trainees then receive clinical training and perform a minimum number of procedures, after which the practitioner, if he or she has successfully completed the clinical practice, can be named eligible to receive medical equipment to be donated to his or her institution. When equipment is installed, a field visit is made by a JHPIEGO consultant to insure the proper use and upkeep of equipment, and the understanding and implementation of standards and procedures. JHPIEGO has trained almost 3000 physicians in laparoscopy techniques between 1973 and 1984. PMID- 2874072 TI - Acute polyhydramnios and cord presentation--complication of chorioangioma of the placenta--a case report. AB - Chorioangioma of the placenta is an uncommon benign tumor of the placenta. Large tumors are rare and they often cause increased maternal morbidity and fetal morbidity and mortality. A patient with continuous abdominal pain at 29 weeks gestation was clinically diagnosed to have acute polyhydramnios. Multiple pregnancy was suspected because of a tense uterus much larger than the dates and three palpable "fetal poles". An ultrasound examination revealed the third pole to be a large chorioangioma. She went into premature labor and a cesarean section was performed because of a cord presentation. Both mother and infant had an uneventful recovery. The complications of chorioangioma is discussed. PMID- 2874073 TI - beta-1-Glycoprotein determination in normal and disturbed pregnancy. AB - beta-1-Glycoprotein (SP1) concentration of 170 women with undisturbed pregnancy under 18th week were taken as reference. SP1 levels of 72 patients with threatening abortion but favorable outcome were compared with those of 70 patients with threatening abortion and subsequent miscarriage. Decreased SP1 levels were determined in most (88%) patients who aborted, whereas 88.8% of patients with favorable outcome had SP1 levels within normal range. The predictive value of SP1 determination in early pregnancies is emphasized. PMID- 2874074 TI - Effect of hormone replacement therapy on anti-thrombin III activity in post menopausal women. AB - Anti-thrombin III is the major inhibitor of activated blood clotting factors. We studied 320 patients with climacteric symptoms who received estrogen replacement therapy to assess the effect of hormone therapy on Anti-thrombin III (AT-III) activity). Of the 320 patients 80 patients received Prempak C (0.625 mg) for 2 years, 82 patients received Prempak C (1.25 mg) for 2 years, 78 patients received Cycloprogynova (1 mg) for 2 years and the remaining 80 patients received Cycloprogynova (2 mg) for 2 years. The mean AT-III activity before, during and 3 months after treatment showed no significant difference in all the four groups of patients. There was no incidence of myocardial infarction or stroke or thrombo embolic disease in this group of 320 patients receiving estrogen replacement therapy. PMID- 2874075 TI - A case of single umbilical artery with various fetal anomalies: correlations between prenatal ultrasonographic diagnosis and autopsy. AB - We report a case of a single umbilical artery with various fetal anomalies, and a comparative study between prenatal ultrasonographic diagnosis and autopsy was done. The prenatal ultrasonographic diagnosis included, atrial septal defect (ASD), ventricular septal defect (VSD), mitral atresia or stenosis and a single great vessel. At autopsy, ASD, VSD, mitral atresia, overriding aorta and pulmonary atresia were evident. In case of other anomalies, the findings in the prenatal diagnosis and at autopsy were encephalocele, adrenal hypoplasia and a single umbilical artery. The ultrasonic detection of these anomalies is discussed and the limitations of this diagnostic method are given attention. PMID- 2874076 TI - The accuracy of hysterosalpingography versus laparoscopy in evaluation of infertile women. AB - Two hundred fifteen infertile women underwent hysterosalpingography (HSG) and laparoscopy. One hundred twenty-eight patients had bilaterally patent tubes on hysterosalpingography. Thirty-one percent of these women had pelvic adhesions diagnosed by laparoscopy. Eighty-seven women had either occluded tubes or suspected pelvic adhesions on hysterosalpingography. Thirty-nine percent of these women had patent tubes without any pelvic pathology on laparoscopy. Inaccurate diagnoses limit the value of hysterosalpingography in evaluation of tubal and peritubal pathology. PMID- 2874077 TI - Childbearing among the Igbos of Nigeria. AB - Traditional Obstetric care among women of the Igbo tribe in Nigeria is described. The role of traditional birth attendants, antenatal care, management of delivery complications, postnatal care and traditional community practices surrounding birth are discussed. PMID- 2874079 TI - Endometriosis in diagnostic laparoscopy in Isfahan, Iran. AB - In 200 consecutive routine diagnostic laparoscopies, 31 cases (15.5%) of endometriosis were found. Of these 200 cases, 131 patients (65.5%) were referred for laparoscopy because of infertility. In 22 (71.0%) out of 31 patients with endometriosis infertility was the indication for laparoscopy. In the remainder of the patients laparoscopy was performed because of other indications. Half of the patients with endometriosis showed moderate or severe degrees of the disease. Seventy-one percent of the patients were below the age of 29. According to our findings, the presumption that endometriosis is a rare disease in Iran is considered to be erroneous. PMID- 2874078 TI - Luteal phase defects in repeated abortion. AB - Fifty women with 2 or more previous first-trimester abortions and 300 infertile patients underwent a luteal phase evaluation by basal body temperature, plasma progesterone, estradiol and prolactin determination, and endometrial biopsy (repeated in a later cycle when the first was defective). An endometrial luteal phase deficiency was detected in 15 (30%) of aborting patients. In 13 (26%) of these women the endometrial defect was associated to normal hormonal levels. This condition was only present in 36 (12%) of the infertility cases (P less than 0.01). We conclude that the possible etiologic role of luteal phase defects in repeated abortion, is by a secretory insufficiency in the endometrial pattern despite normal plasma hormonal levels. PMID- 2874080 TI - In-hospital maternal mortality risk by cesarean and vaginal deliveries in two less developed countries--a descriptive study. AB - Cesarean deliveries are increasing in both developed countries and less developed countries (LDCs). Recent studies in the U.S. have revealed a significantly higher mortality risk for women who delivered abdominally than for those who delivered vaginally, even when the effect of the conditions which necessitated cesarean delivery was taken into account. We chose for study from an international maternity monitoring network, five centers from two LDCs that reported an in hospital maternal mortality rate (MMR) of around 10 per 1000 parturient women. The pooled data revealed an MMR of 5.1 per 1000 women with vaginal deliveries. For women with cesarean delivery, the total MMR was 36.2 and the MMR attributable to cesarean section was estimated to be 12.8; both rates were per 1000 procedures. The leading cause of death was eclampsia for the vaginal deliveries and sepsis for the cesarean deliveries. The risk of maternal mortality inherent with the cesarean section procedure per se (not counting the risk associated with the labor and delivery complications that necessitated cesarean section) as well as the practical avoidability of maternal deaths for either mode of delivery in these LDC hospitals are discussed. PMID- 2874081 TI - Serum ferritin values in Nigerian pregnant women. AB - Serum ferritin values have been studied in 28 indigenous Nigerian pregnant women during the second and third trimesters of pregnancy. The mean serum ferritin value in the second trimester is higher than that in the third trimester, however, the difference is not statistically significant. When our results are related to those of Fenton and co-workers in 1977 (Fenton V, Cavill I, Fisher J: Iron stores in pregnancy. Br J Haem 37: 145, 1977) it appears that serum ferritin decreases in early pregnancy and that this decrease is maintained through the second and third trimesters and towards term, irrespective of adequate iron supplementation. It also seems that the pre-pregnancy serum ferritin level is achieved 5-8 weeks post-delivery. Our results also underline the sensitivity of serum ferritin evaluation in pregnancy, and reinforce the concept that fetal requirement for iron occurs significantly during the later half of pregnancy. PMID- 2874082 TI - Indications and results of metroplasty in uterine malformations. AB - During 14 years, 430 women with some type of congenital uterine malformation were discovered by different methods, with a rate of 1 in 137 deliveries. In only 17 was metroplasty indicated, because of very poor reproductive performance; out of 42 desired pregnancies, only 14.3% live births resulted. The abortion rate was 65.2%, and there were 13% premature deliveries. The operations performed included the Strassmann type in 13, the Tompkins technique in three and the Jones operation in one. After the metroplasty, out of 27 completed pregnancies the rate of abortions fell in 14.8% (P less than 0.00003) and the rate of live births rose to 85.2% (P less than 0.00003). There is no doubt that when the indication for metroplasty is strictly imposed, the staff is well versed in the different types of operations and the treatment is done in a center which has acquired competence, the improvement in reproductive performance can be quite impressive. PMID- 2874083 TI - Acceptance of contraceptive practice by grandmultiparae in Benin City, Nigeria. AB - Five hundred sixty grandmultiparous women were interviewed as to their contraceptive awareness, desirability and use in the three major hospitals in Benin City, Nigeria, between October 1, 1980 and September, 1981. Their parity ranged from 5 to 14 with a mean of 6.7. There was high level of awareness of contraceptive availability and usefulness (65%), but low level of practice (27.1%). The main causes of the low practice level included opposition from husband and other relatives, complications of previous methods used and the desire to have a large family. Oral contraceptives were the preferred method, followed by intrauterine devices. Educational attainment had a positive relationship to acceptance of contraceptive practice. We believe that with more concerted effort at family planning counseling, the community will be rid of the hazards and menace of grandmultiparity. PMID- 2874084 TI - Prognostic value of a malignancy grading system in treatment of recurrent cervical carcinoma. AB - A malignancy grading system (MGS) comprising 8 histopathological parameters has been used to evaluate the response rate and prognosis for patients receiving chemotherapy for recurrent cervical carcinoma. Seventy-two women were treated with an adriamycin-cyclophosamide-vincristine (ACO) regimen or bleomycin adriamycin-cisplatin (BAD) regimen. The mean value in the MGS was 16.7 for the primary tumors and 17.4 for the recurrences. Correlations between the individual parameters of the MGS when used on the primary tumors and on the recurrences were low. Only parameters 7 (vascular invasion) and 8 (lymphocytic response) were significantly higher in the recurrences. Responders had significantly longer survival than non-responders (P less than 0.001), but the two groups did not differ regarding the malignancy scores for the 8 individual parameters nor for the MGS sums. PMID- 2874085 TI - Broad spectrum antibiotics as short term prophylaxis for elective abdominal hysterectomy: comparison of mezlocillin, cefazolin and placebo. AB - A prospective randomized placebo controlled double-blind study was conducted in order to evaluate the effect of short term perioperative antibiotic prophylaxis on patients undergoing elective abdominal hysterectomy. Fifty-two patients received 3 doses of 0.5 g cefazolin, 54 patients received 3 doses of 1 g mezlocillin and 53 patients received placebo. Postoperative infectious morbidity and the rate of pelvic cellulitis were significantly lower in either antibiotic group in comparison to the placebo group, but neither drug proved to be superior in this respect. The fever index was significantly lower in the mezlocillin group in comparison to both cefazolin and placebo groups. It was thus concluded that antibiotic prophylaxis has a beneficial effect on patients undergoing abdominal hysterectomy and both drugs--cefazolin and mezlocillin--seem to be equally effective. PMID- 2874086 TI - The role of obstetric factors in perinatal mortality trends. AB - In the Perinatal Unit of the New Jersey Medical School, Newark the combined neonatal mortality and stillbirth rates declined from more than 51 per 1000 to less than 17 per 1000 between 1971 and 1983. This change is comparable to the reduction of perinatal mortality rates nationwide since the Second World War. Because the improvement in the fetal and neonatal survival rates occurred in a static population and against well identifiable changes in the structure, equipment, policies and management patterns of the obstetric unit, it was possible to assess the impact of various factors upon perinatal outcome. In the environment of this institution adherence to conservative concepts of obstetric management, avoidance of manipulative and extraction procedures, an increase of the rate of cesarean sections from about 7 to 15% and emphasis upon infection control appeared to be the crucially important factors. Antepartum sonography and fetal stress and non-stress testing significantly impacted upon the results. The role of intrapartum electronic monitoring was less clearly definable and seemed to be effective only in the hands of experienced physicians. The results did not seem to be adversely affected by the fact that the program de-emphasized invasive procedures, including fetal scalp pH sampling. PMID- 2874087 TI - Antimicrobial properties of amniotic fluid from some Nigerian women. AB - Fifty-one amniotic fluids were aspirated via the vaginal route from 51 pregnant Nigerian mothers. Their antimicrobial activity was tested against Staphylococcus aureus, Escherichia coli and Candida albicans. Inhibition rates were 39.2% for Staph. aureus 19.6% for E. coli and 41.2% for C. albicans. The overall inhibitory capacity was 64.7%. Sixteen fluids (31.4%) were active against one organism, three fluids (5.9%) were active against two organisms and one fluid (2%) was active against the three organisms. Age, parity and meconium-staining of liquor had no correlation with antimicrobial properties. The possible explanations for these are given. PMID- 2874088 TI - The role of phosphorylation/dephosphorylation of acetyl-CoA carboxylase in the regulation of mammalian fatty acid biosynthesis. PMID- 2874089 TI - Mechanisms involved in the short-term regulation of acetyl-CoA carboxylase by insulin. PMID- 2874090 TI - Plant acetyl-CoA carboxylase. PMID- 2874091 TI - Modulation of insulin secretion by pancreatic ganglionic nicotinic receptors. AB - Autonomic ganglia may be regulated, in part, by nicotinic receptors. To test whether basal insulin secretion may be modulated by an endogenous pancreatic ganglionic mechanism, the effects of ganglionic pre- and postsynaptic nicotinic receptor antagonism were studied in the in vitro canine pancreas. Combined infusion of atropine, phentolamine, and propranolol had no affect on insulin secretion (P less than .30). Presynaptic nicotinic receptor blockade by beta bungarotoxin (beta-BuTX) in combination with atropine and phentolamine reduced mean insulin secretion (78 +/- 18 U/ml, P less than .0025) from preinfusion concentrations (287 +/- 43 U/ml). The decrease in insulin secretion resulting from BuTX, atropine, and phentolamine was prevented by the addition of either specific postsynaptic nicotinic receptor blockade by alpha-bungarotoxin (P less than .05) or propranolol (P less than .005). Because it is known that postsynaptic nicotinic receptor agonism may stimulate the intraganglionic release of norepinephrine, these results suggest that nicotinic receptors are present at the ganglionic level in the pancreas and modulate insulin secretion by a complex intraganglionic mechanism. The postulated ganglionic nicotinic receptor-mediated mechanism may operate by the interaction of a beta-adrenergic inhibitory component, which may be activated by intraganglionic norepinephrine, and a stimulatory nonmuscarinic nonadrenergic (possibly peptidergic) component, which may be activated in the absence of intraganglionic norepinephrine. PMID- 2874092 TI - Structural investigations of the diffusion-zone of soldered dental gold and base metal alloys. PMID- 2874093 TI - [Myocardial mechanical injury in acute ischemia: a pathophysiologic and histopathologic review]. AB - The recognition of histopathologic substrates of myocardial contractile damage in human acute ischemia is still very poor, notwithstanding the impressive advances in the inherent clinical diagnostic technology and concepts. The first and foremost inotropic abnormality ensuing ischemia, easily taken for atonic in origin, actually consists of a pathologic contracture of the injured myocardium, depending upon abrupt fall of ATP, and defective extrusion calcium pump with persistence of actomyosin rigor-complexes. In sustained ischemia, further membrane damage exposes the myocell to massive calcium intrusion, with eventual precipitation of it and cell death (reperfusion stone-heart). In case of transient, "hit and run" ischemia, the "stunned" myocardium undergoes prolonged contractile abnormalities. In keeping with fundamentals in pathophysiology of contraction, ischemic myofibrils in human hyperacute infarct, showed spare I bands, accounting for contracture and followed by loss of the regular cross striation register; then, groups of adjacent sarcomeres were seen to join into true "contraction" bands, with Z lines impinging upon A bands and obliterating the I bands. Coagulative denaturation of contractile proteins follows, presenting as irregular, amorphous degeneration stripes astride irreversibly damaged myocells. As such, these cells can be passively overstretched by the nearby functioning muscle. In turn, the fixed waviness of viable, acutely ischemic myocardium was thought to configure, histologically, the loss of ATP-dependent "plasticity" of myofilaments, in a state of contracture. The "relaxant effect" of inotropic-chronotropic-positive catecholamines, favoring diastole, has been also pointed out. The present microscopic findings are cogent to clinicopathologic problems of coronary ischemia-reperfusion, and sudden death from cardiogenic shock. PMID- 2874094 TI - Mucus, gastrin and somatostatin cells in cultured rat antral mucosa: immunofluorescence, ultrastructural and radioimmunological studies. AB - Cells were isolated from the gastric antrum of newborn rats (7 and 10 days old) with the intent of studying mucus, gastrin (G), and somatostatin (D) cells. These cells were maintained in culture for 20 days. Their secretory properties were studied in vitro by cytochemical, immunocytochemical and radioimmunological methods. In vitro, mucus cells as well as G and D cells synthesized their secretory products intensely for the first 48 h, but beyond this point, their activity decreased. Mucus cells had a high rate of multiplication and formed sheets of epithelial cells in vitro. Their PAS-positive secretions were synthesized up until the 7th day of culture. During the first 3 days of culture, gastrin cells secreted detectable amounts of the hormone in the culture medium, but afterwards their secretion decreased. Somatostatin cells remained active until at least the 7th day of culture. They displayed long cytoplasmic processes which may serve as a means of communication with neighboring cells. Using ultrastructural techniques, mucus and endocrine cells were found to persist in culture. From a morphological point of view, they appeared similar to the cells found in the original antral tissue and this is an argument for the persistence of the secretory properties in cultivated cells. This experimental model appears to be reproducible and may be useful in the study of secretions of somatostatin, gastrin and mucus in the gastric antrum of the rat. PMID- 2874095 TI - [Digestive manifestations of vasculitis]. PMID- 2874096 TI - Cholinergic effects of histamine-H2 receptor antagonists partly through inhibition of acetylcholinesterase. AB - The effects of histamine H2-receptor antagonists on acetylcholinesterase and pseudocholinesterase activity were studied. All H2-antagonists tested inhibited both enzyme activities dose-dependently. The potency of inhibitory activity of H2 antagonists on acetylcholinesterase estimated from median inhibitory dose were in the following order of decreasing activity: ranitidine greater than TZU-0460 greater than cimetidine greater than YM-11170, whereas that on pseudocholinesterase were TZU-0460 greater than ranitidine greater than cimetidine greater than YM-11170. As the effects derived from the inhibition of acetylcholinesterase by H2-antagonists may affect intestinal motility, we studied ileal muscle contractions. Ranitidine had the most potent stimulating effect on contraction, the pattern of which was similar to physostigmine and was blocked by atropine and morphine. YM-11170 had a weak action on muscle contraction and cholinesterase activities. PMID- 2874097 TI - DA1 receptor mediates dopamine-induced relaxation of opossum lower esophageal sphincter in vitro. AB - The objective of the present experiments was to determine the specific receptor subtype through which dopamine (DA) receptor agonists relax the lower esophageal sphincter in vitro. Opossum lower esophageal sphincter smooth muscle strips were placed in oxygenated Krebs' solution containing propranolol and cocaine. The tissues were placed at a tension that gave maximum relaxation to electrical field stimulation and were then pretreated with phenoxybenzamine. The effects of DA, and the DA receptor agonists epinine and apomorphine were determined. In addition, agonist responses were studied in the presence of the selective DA2 receptor antagonist domperidone, a mixed DA1/DA2 receptor antagonist metoclopramide, and the selective DA1 receptor antagonists bulbocapnine and SK&F 83566. The DA agonists relaxed the smooth muscle strips in the following order of potency: DA greater than epinine greater than apomorphine. Domperidone did not antagonize DA- or apomorphine-induced relaxation. Metoclopramide failed to alter DA-induced relaxation. Bulbocapnine and SK&F 83566 significantly inhibited the relaxation induced by DA. These data indicate that DA-induced lower esophageal sphincter relaxation in vitro is mediated by DA1 receptors. PMID- 2874098 TI - Experimental diabetic diarrhea in rats. Intestinal mucosal denervation hypersensitivity and treatment with clonidine. AB - Diarrhea in streptozocin-induced chronically diabetic rats is caused by an impaired adrenergic regulation of intestinal fluid and electrolyte transport. Stimulation of alpha 2-adrenergic receptors on enterocytes normally promotes NaCl absorption and inhibits HCO3 secretion. The purpose of this study was to determine if adrenergic denervation of intestinal mucosa in chronically diabetic rats alters postsynaptic receptor response, and if the alpha 2-adrenergic agonist clonidine could correct observed fluid malabsorption. Mucosal norepinephrine stores, a measure of adrenergic tone, were markedly reduced in diabetic rats compared with nondiabetic littermates. In vitro, short-circuit current changes to exogenously added l-epinephrine were significantly greater in diabetics, suggesting that denervation hypersensitivity was due to increased numbers of postsynaptic alpha 2-adrenergic receptors. In vivo loop studies demonstrated net fluid secretion in the ileum and colon of diabetics. In diabetics, clonidine reversed the secretion to absorption, but it had no effect on fluid absorption in controls. We conclude that diabetic diarrhea in streptozocin-induced chronically diabetic rats is due to impaired adrenergic regulation of mucosal ion transport, accompanied by a postsynaptic denervation hypersensitivity that can be reversed by clonidine, and accompanied by net intestinal fluid secretion that can be effectively reversed with clonidine. PMID- 2874099 TI - Diffuse somatostatin-immunoreactive D-cell hyperplasia in the stomach and duodenum. AB - This paper presents the first case of extensive, diffuse, somatostatin immunoreactive D-cell hyperplasia in the human stomach and duodenum. It occurred in a 37-yr-old woman, who showed clinical signs of dwarfism, obesity, dryness of the mouth, and goiter. The density of the distribution of D cells was increased 39-fold in the stomach fundus, 23-fold in the proximal antrum, 25-fold in the distal antrum, and 31-fold in the upper duodenum in comparison with normal values. At the same time, the gastrin-immunoreactive cells were increased 2.3 fold in the antrum. Although the range in size of the D cells was within normal limits in all regions examined, the G cells showed pronounced hypertrophy of up to 127%. A possible relationship between the immuno-histochemical findings and the clinical picture is discussed. PMID- 2874100 TI - Alpha 2-adrenergic agonists: a newer class of antidiarrheal drug. PMID- 2874101 TI - Experimental studies of ageing: behavioural and physiological correlates. AB - Many brain modifications have been described in ageing: cognitive functions, learning ability and memory retention decline very frequently. It is not clear whether the observed deficits are related to alterations in memory processes (short- or long-term memory), in memory modulation or in nonassociative factors. We tried to correlate the morphological neurophysiological and neurochemical changes in aged brain with the decline in learning behaviour. Psychopharmacology of ageing is developing quickly, but presently no data are completely convincing, even though prospects are interesting. PMID- 2874102 TI - Alzheimer's disease. AB - Alzheimer's disease and senile dementia are considered primary degenerative disorders of the brain. The delimitation of the two disorders is their onset: whether it is before or after the age of 65 years. As the neuropathological findings in the two disorders are similar they sometimes are sampled together. Biochemical investigations have shown extensive and severe disturbances of neurotransmitters in the brain of patients with Alzheimer's disease and senile dementia. Although the acetylcholinergic system is severely damaged and has been given special etiological importance, it seems that also the monoaminergic, the GABA-ergic and the neuropeptidergic systems are deranged. The extensive damage to the neurotransmitter systems indicates an etiology beyond the transmitter level. It is natural to assume that the disturbed neurotransmitters have pathogenic importance for the disorder. Pharmacological treatment trials have been performed in which the failing systems are substituted. Hitherto, however, these trials have not been as successful as expected. PMID- 2874103 TI - Sulphasalazine associated pancytopenia may be caused by acute folate deficiency. AB - Agranulocytosis and aplastic anaemia associated with sulphasalazine are well recognised, but pancytopenia caused by acute megaloblastic arrest of haemopoiesis while taking sulphasalazine has not previously been described. We report three patients who, after taking sulphasalazine for over two years, suddenly developed severe pancytopenia with gross megaloblastic changes in the marrow. In two patients there was a good response to high dose oral folic acid but the third required folinic acid. The mechanism appears to be acute folate deficiency, and the requirement for folinic acid in one case suggests that the known inhibition of folate metabolism by sulphasalazine also contributes. The syndrome appears to be associated with high dosage and slow acetylator status. The drug has been successfully restarted at reduced dosage with folate supplements in two patients both of whom were slow acetylators. In the third case, whose acetylator status is not known, progression of her disease led to colectomy. PMID- 2874104 TI - [Effects of somatostatin and its analogue, des (Ala1, Gly2) [D-Trp8, D-Asu3,14] somatostatin (SS-1), on gastric mucosal blood flow and gastric secretion]. AB - The inhibitory effects of somatostatin and its analogue (SS-1) on gastric mucosal blood flow (MBF) and gastric secretion were studied using bethanechol and pentagastrin as stimulants in anesthetized rats. In the present study, the inhibitory action of SS-1 was particularly investigated, regarding somatostatin as the control compound. Pretreatment with SS-1 at 1, 10, 30, or 100 micrograms/kg, i.v. (single dosing), inhibited the increase of MBF and gastric secretion stimulated by bethanechol in a dose-dependent manner. SS-1 showed no marked difference from somatostatin in terms of the degree and manner of the inhibition until 30 min after treatment. At 90 min, however, SS-1 still showed an inhibitory action, which was more prominent in gastric secretion than in MBF. Thus, SS-1 had a longer duration of action than somatostatin. Generally, SS-1 and somatostatin inhibited MBF to the same degree, whereas SS-1 inhibited gastric secretion more strongly than somatostatin. When pentagastrin was used to stimulate MBF and gastric secretion, SS-1 inhibited MBF and gastric secretion to the same degree as did somatostatin, but again, SS-1 had a longer duration of action than somatostatin. PMID- 2874105 TI - [Effect of anxiolytic drugs on the development and healing process of stress ulcer: application of endoscopic observation]. AB - The present study was conducted to investigate the effect of anxiolytic drugs on the development and healing process of gastric mucosal lesions (GML). In order to produce the GML in mice and rats, we employed a communication box paradigm which can differentially induce a physical and psychological stress. The following drugs (2.5, 50.0, 7.5 mg/kg for mice and 5.0, 10.0 mg/kg for rats) were administered orally: diazepam, clotiazepam, ethyl loflazepate and vehicle (0.5% CMC solution). To define the drug effects on the healing process of GML in rats, we applied an endoscopic technique using the ultra-thin fiberscope. The endoscopic observation was performed under ether anesthesia at 1, 24, 36 and 60 hr after the termination of stress. Both diazepam and ethyl loflazepate significantly suppressed the development of GML in mice, while the preventive effect of clotiazepam was less potent than those of the other anxiolytics. In rats, only ethyl loflazepate showed a significant preventive effect. The curative effect of clotiazepam on the healing process of GML in rats was clearly demonstrated, whereas diazepam was ineffective on the healing process. Ethyl loflazepate also showed a tendency to facilitate the healing process of GML. The present study suggests that the application of the endoscopic technique to rats may provide a potential tool for evaluating the curative effect of drugs on the GML. PMID- 2874106 TI - [Drug treatment of pain. 2: Properties of centrally acting analgesics and rules for prescribing them]. PMID- 2874107 TI - Effect of beta h-endorphin on release of insulin by rabbit pancreas in response to four secretagogues: comparison with somatostatin and epinephrine. AB - Previous work showed beta h-endorphin inhibits glucose-stimulated secretion of insulin by rabbit pancreas slices. This study, also conducted with rabbit pancreas slices, compared the antisecretagogue actions of beta h-endorphin, somatostatin 1-14, and epinephrine versus four secretagogues, glucose, mannose, leucine and potassium chloride. All three antisecretagogues inhibited all four secretagogues. The order of potency of the antisecretagogues varied according to secretagogue. Naloxone antagonized only beta h-endorphin among the three antisecretagogues, and phentolamine antagonized only epinephrine. PMID- 2874108 TI - Blockade of alpha 2-adrenoreceptor prevents the growth hormone releasing effect of FK 33-824 in the dog. PMID- 2874109 TI - New diagnostic markers of alcohol abuse. PMID- 2874110 TI - Managing an acutely manic 17-year-old girl with neuroleptic malignant syndrome. PMID- 2874111 TI - Loss of susceptibility to complement lysis in Entamoeba histolytica HM1 by treatment with human serum. AB - Entamoeba histolytica HM1, exposed to a series of treatment with normal human serum (NHS), progressively lost susceptibility to complement lysis. Trophozoites were incubated daily with unheated or heat-inactivated NHS for 2 hr at 36 degrees, starting with 10% v/v serum and increasing by 5% every 3 days up to 40% NHS. Resistance to complement lysis was also obtained with two different HM1 clones but not with the low virulent strain HK9. Induction of resistance dependent on the number of NHS treatments, with a maximal 50% reduction occurring after 11 treatments. Susceptibility to complement-dependent lysis was regained 6 weeks after serum treatments were terminated, suggesting that resistance to lysis was an acquired rather than a genetic property. PMID- 2874112 TI - Analysis of H-2-linked immune responses involved in resistance to AKR tumor growth. AB - H-2-associated immune response gene(s) govern resistance to growth of a spontaneous AKR lymphoma, BW5147. The antigenic specificities recognized by the anti-BW5147 humoral response have been characterized and include: Thy-1, a T-cell differentiation antigen; gp70, a retroviral envelope protein; and several previously uncharacterized proteins, including a 78 000 molecular mass protein, p78, which is restricted to expression on BW5147 cells and five phosphoproteins with molecular masses of 33 000, 29 000, 23 000, 17 000, and 16 000. Only mice which are able to respond to Thy-1, p78, and the phosphoproteins can survive an inoculation of BW5147. Thus, resistance to BW5147 is complex and involves multiple antigens with possible roles in tumor rejection. PMID- 2874113 TI - Efficacy of arosurf--a monomolecular surface film, in controlling Culex quinquefasciatus Say, Anopheles stephensi Liston & Aedes aegypti (L). PMID- 2874114 TI - Virulence properties of Escherichia coli strains in patients with chronic pyelonephritis. AB - In 50 Escherichia coli strains obtained from the bladder puncture urine of patients with chronic pyelonephritis, determinations of virulence properties were performed. All of the E. coli strains isolated from 26 acute episodes of pyelonephritis were found in the smooth form. 30% possessed K 1 antigen, 77% showed the ability to form hemolysin and 30% produced colicin V (aerobactin). Fimbriae (detected by mannose-resistant hemagglutination) were registered in 81%, and plasmids ranging between 50 and 70 Md were demonstrated in 70% of the bacteria. In contrast to this, only 70% of the E. coli strains isolated from 24 patients at an inactive stage of pyelonephritis were found in the smooth form; 10% of these encoded K 1 antigen, 20% hemolysin and 10% colicin V. Plasmids in the range 50 to 70 Md could be found in 30%. On the basis of multivariate analysis of variance and discriminant analysis, it was confirmed that uropathogenic strains possess several virulence properties, mannose-resistant hemagglutination being of particular importance. PMID- 2874115 TI - IL-2- and IL-2-R- independent proliferation of T-cell lines from adult T-cell leukemia/lymphoma patients. AB - Human T-cell leukemia/lymphoma virus I (HTLV-I) is known to be associated with adult T-cell leukemia/lymphoma (ATL) as an etiological agent. The mechanism of leukemogenesis by HTLV, however, is still obscure. Two hypotheses have been proposed concerning abnormalities in IL-2 production and its receptor (Tac antigen) expression based on the experimental observations of IL-2-dependent ATL cell lines. In this study, we examine these hypotheses by using 3 leukemic T-cell lines from 3 Japanese patients with ATL. These cell lines were cultivated and established without addition of IL-2 to the culture medium. Cell-surface phenotype analysis by immunofluorescence with monoclonal antibodies (MAbs) and IL 2 binding assays revealed that one of the ATL cell lines, HPB-ATL-2, expresses only a minimal amount of IL-2 receptor (IL-2-R) on the cell surface and binds less radiolabelled human recombinant IL-2 than the other highly Tac-positive cell lines. Expression of Tac antigen in all ATL cell lines was not affected by IL-2, anti-Tac MAb or the tumor-promoter phorbol ester in the culture medium. The culture supernatant from these cell lines showed no IL-2 activity toward Con-A stimulated human peripheral blood lymphocytes, and their growth was not affected by additional IL-2 in cultures. IL-2-independent growth and constitutive expression of its receptors on the cell surface were evident in our ATL cell lines. However, dense expression of IL-2 receptors was not essential for stimulation of leukemic proliferation of T cells by HTLV-I. Trans-activation of the PX40 gene product of HTLV-I for activation of IL-2-R gene might not be coincidentally associated with stimulation for cell proliferation. PMID- 2874116 TI - Plasma concentrations of astemizole in patients with terminal renal insufficiency, before, during and after hemodialysis. AB - Four patients undergoing hemodialysis because of terminal renal insufficiency have taken 10 mg of astemizole on two consecutive days. The elimination was followed for 7 days and was found not to be delayed. During dialysis no decrease of the plasma levels of astemizole and its hydroxylated metabolites were observed. On the contrary, a small nonsignificant increase was found which can be explained by the thickening of the blood after ultrafiltration. It can be concluded that astemizole cannot be eliminated by dialysis because of its high protein binding capacity. PMID- 2874117 TI - The effect of six beta-adrenolytics and labetalol on hepatic biotransformation studied by antipyrine test, in man. AB - The study was aimed at a comparison of the effects of various beta-blockers (propranolol, pindolol, nadolol, atenolol, metoprolol, acebutolol, labetalol) on hepatic biotransformation within the short- and long-term treatment. The study was undertaken in 125 patients with arterial hypertension and/or coronary heart disease. The rate of hepatic metabolism was estimated by antipyrine test. After several months' administration of "pure" beta-adrenolytics the antipyrine half time increased (means + SD) from 16.6 +/- 4.4 to 22.1 +/- 8.0 h (p less than 0.01), whereas antipyrine clearance decreased from 27.4 +/- 11.5 to 21.9 +/- 8.7 ml X min-1 (p less than 0.01). Deterioration of antipyrine elimination following beta-adrenolytics administration occurred independently of such properties as cardioselectiveness, intrinsic sympathomimetic activity, membrane stabilizing activity and the liver first-pass effect. After three months' labetalol (alpha + beta-blocker) administration, the antipyrine half-time decreased from the average 18.5 +/- 5.1 to 15.0 +/- 4.4 h (p less than 0.05), whereas its clearance increased from 30.3 +/- 2.7 to 36.3 +/- 10.8 min-1 (p less than 0.05). The results indicate that labetalol accelerates the rate of hepatic biotransformation as opposed to "pure" beta-adrenolytics, deteriorating the hepatic metabolism efficiency. PMID- 2874118 TI - Synthesis of sequences 1-16 and 63-95 of Cerebratulus lacteus toxin AIII. Hemolytic activity in a toxin fragment. AB - Sequences 1-16 and 63-95 of C. lacteus toxin AIII were synthesized on benzhydrylamine and PAM resins respectively; the crude peptide products released by HF contained 90 and 33% of the target peptides. Fragment 63-95 was nearly a full agonist, producing greater than 90% of the hemolytic activity of the intact toxin molecule at 10(3)-fold higher concentrations. Fragment 1-16 had no activity. PMID- 2874120 TI - Primary squamous cell carcinoma of pleura. PMID- 2874119 TI - Heterogeneous expression of two oncodevelopmental antigens, CEA and SSEA-1, in colorectal cancer. AB - Colorectal carcinomas are composed of heterogeneous cell subpopulations which may be instrumental in conferring metastatic potential and therapeutic refractoriness to these tumours. To assess cellular heterogeneity, the expression has been examined of two oncodevelopmental antigens, carcinoembryonic antigen (CEA) and stage-specific embryonic antigen 1 (SSEA-1), by double immunofluorescence microscopy on 11 human colorectal carcinomas. Although both antigens were expressed in each tumour, their regional and cellular locations differed considerably. SSEA-1 expression was rarely expressed in poorly differentiated cancers but was enhanced with increasing degrees of differentiation. CEA expression was independent of histological differentiation. SSEA-1 was expressed with similar frequency in cell membranes, cytoplasm, and glandular contents regardless of degree of differentiation. Cytoplasmic staining with CEA however, was limited to more poorly differentiated tumours. In normal mucosa remote from the tumours and transitional mucosa adjacent to them, SSEA-1 stained only a few lower crypts whereas CEA stained a majority of both upper and lower crypts. Although biochemical studies have indicated that the SSEA-1 epitope may reside on CEA molecules, the fact that colon cancer tissues express these two antigens quite heterogeneously suggests differences in antigenic processing which may be dependent upon the degree of cellular differentiation. PMID- 2874121 TI - Clinical assessment score and peak expiratory flow rate. Correlation in acute childhood asthma. PMID- 2874122 TI - Sudden infant death in five consecutive siblings. PMID- 2874123 TI - Hepatic enzyme changes in bovine hepatogenous photosensitivity caused by water damaged alfalfa hay. AB - In the winter of 1983, practitioners reported extensive photosensitization in 7 herds of cattle. All herds had a history of having been fed water-damaged alfalfa hay. A cow from one herd was referred to the veterinary teaching hospital at Oklahoma State University. In this herd of approximately 40 adult Polled Herefords, all cattle had had some degree of clinical involvement over the past 4 to 6 weeks. Clinical signs included scaling and erythema of sparsely haired skin, muzzle, and teats, as well as icterus, anorexia, and weight loss. One cow died, and the remaining cattle recovered over an 8- to 10-week period after removal of the hay from the ration. In the referred cow, values for total and conjugated bilirubin, BUN, creatinine, sorbitol dehydrogenase, serum alkaline phosphatase, serum aspartate transaminase, and serum gamma-glutamyl transferase were higher than normal. In the herd of origin, extremely high serum gamma-glutamyl transferase values (180 to 1,400 IU/L) persisted (normal, 2 to 35 IU/L). Feeding the same alfalfa hay to 2 clinically normal cows reproduced the syndrome. The characteristic hepatic lesion was bile duct necrosis, with secondary bile duct hyperplasia. PMID- 2874124 TI - No significant changes in adult T-cell leukemia virus infection in Okinawa after intervals of 13 and 15 years. AB - Two separate studies were carried out between 1968 and 1984; a total of 2,021 serum samples from healthy subjects were collected in two districts of Okinawa-on Iriomote Island and in Ishigaki City. The first samples were collected in 1970 on Iriomote Island and in 1968 in Ishigaki City. The second samples were collected after an interval of 13 years in Ishigaki City and after an interval of 15 years on Iriomote Island. These serum samples were tested for the presence of antibody to adult T-cell leukemia-associated antigen (anti-ATLA). The overall prevalence of anti-ATLA in both areas combined was 9.9% from 1968 to 1970 and that from 1981 to 1984 was 8.9%. At both times, anti-ATLA prevalence increased with age and was higher in females than in males. No significant changes in anti-ATLA prevalence was observed: after intervals of 13 and 15 years, the prevalence decreased from 10.2 to 9.9% in Ishigaki City and from 9.4 to 8.2% on Iriomote Island. These data suggest that there has been no significant change in the rate of infection with adult T-cell leukemia virus in recent years in the areas studied. PMID- 2874125 TI - Neurotransmitter-related immunocytochemistry of the organ of Corti. AB - The principles of immunocytochemistry were outlined in 1942 by Coons et al. and in the 1970's immunocytochemistry emerged as a powerful method for identifying structures and tracing pathways in the nervous system. It now plays a fundamental role in the neuroanatomical and histochemical analysis of the central nervous system. The first immunocytochemical studies of the mammalian cochlea were reported in 1980, from three different laboratories. Since then many studies on cochlear immunocytochemistry have been carried out, concerned with questions about neurotransmitter candidates or about structural proteins. This review describes immunoreactivity of enkephalin, choline acetyltransferase (ChAT), glutamate decarboxylase (GAD), gamma-aminobutyric acid (GABA), aspartate aminotransferase (AATase) and glutaminase (GLNase) in the organ of Corti. ChAT is the enzyme that catalyzes the synthesis of acetylcholine (ACh). GAD is the terminal enzyme in the biosynthesis of the inhibitory neurotransmitter GABA. AATase and GLNase are two enzymes involved in the metabolism of the excitatory neurotransmitter candidates aspartate and glutamate. We have much relied on surface preparations of the organ of Corti. We have also used cryostat sectioning of the cochlea, particularly when there was a need to apply a number of different antisera to comparable preparations from one and the same cochlea. We have used immunofluorescence and immunoperoxidase procedures. Immunoperoxidase procedures have given us better signal noise ratio for specific immunoreactivity (in surface preparations) than has immunofluorescence. Occasionally, to achieve maximal resolution of surface preparations in light microscopy studies, we have used enhanced contrast video display. We have found immunoreactivity in efferent fibers in the organ of Corti following the application of antisera to enkephalin, ChAT, GAD, GABA, AATase and GLNase. Most of these different antisera give different distributions of immunoreactivity and other antisera have evoked no immunoreactivity in the organ of Corti. To the best of our knowledge, the cells of origin of efferent axons and terminals in the organ of Corti are located in the brainstem. Originally described as crossed and uncrossed olivocochlear neurons, these efferents have recently been classified into a medial and a lateral system predominantly innervating, respectively, the outer hair cell region and the inner hair cell region. However, our findings on the distribution of GAD- and GABA-like immunoreactivity indicate that there may be more than two different systems of efferents in the organ of Corti, as previously suggested by Schwartz and Ryan (1983). PMID- 2874126 TI - Adverse reactions to sudden stoppage of drugs. PMID- 2874127 TI - Psychotropic medication in adolescents: a review. AB - All published articles of double-blind, controlled studies of drug treatment of mental disorders in adolescents are reviewed. The evidence for efficacy ranges from suggestive to nonexistent, without any match of drug and disorder showing definitive evidence, either because of the limited number of studies available or because these studies have less than clear findings. Special considerations in the study of adolescent psychopharmacology are addressed, and a practical approach to drug treatment making the best use of the limited information available is offered. PMID- 2874128 TI - Low-sedation potential of buspirone compared with alprazolam and lorazepam in the treatment of anxious patients: a double-blind study. AB - Buspirone was compared to alprazolam and lorazepam in the treatment of generalized anxiety disorder in a 4-week, double-blind study of 60 patients. All three medications were effective and similar in producing significant reductions in anxiety as assessed by standardized anxiety rating scales and by global evaluations of patients by physicians. There were significant differences in drowsiness, lethargy, and/or fatigue: fewer patients in the buspirone group than in the alprazolam group (16% vs. 60%, respectively; p less than .01) or the lorazepam group (16% vs. 65%, respectively; p less than .0003) experienced these undesirable side effects. This demonstration of similar effectiveness and superior safety would favor buspirone in the treatment of generalized anxiety disorder. PMID- 2874129 TI - Premenstrual tension syndrome in rapid-cycling bipolar affective disorder. AB - Premenstrual tension syndrome (PMS) and rapid-cycling bipolar affective disorder have similarities of symptoms, cyclical mood swings, and putative neurotransmitter dysfunction. The possible relationship between these disorders was assessed by evaluating 25 patients with rapid-cycling disorders and 25 normal controls for PMS symptoms. Patients with rapid-cycling affective disorder had an increased tendency to have more severe forms of PMS. In addition, patients with rapid-cycling disorders and more severe forms of PMS tended to cycle more frequently. The significance of this finding and its clinical implications are discussed. PMID- 2874130 TI - Relationship between dystonia and serum calcium levels. AB - The relationship between acute dystonic reactions and serum calcium levels in 17 acutely psychotic patients was studied. Previous studies have implicated an association between a lowered serum calcium value and acute dystonia. This study failed to note a significant incidence of hypocalcemia in a group of psychotic patients. It is not known whether other factors related to calcium-magnesium balance may be related to dystonia. PMID- 2874131 TI - Clathrin-coated vesicles contain two protein kinase activities. Phosphorylation of clathrin beta-light chain by casein kinase II. AB - Incubation of clathrin-coated vesicles with Mg2+-[gamma-32P]ATP results in the autophosphorylation of a 50-kDa polypeptide (pp50) (Pauloin, A., Bernier, I., and Jolles, P. (1982) Nature 298, 574-576). We describe here a second protein kinase that is associated with calf brain and liver coated vesicles. This kinase, which phosphorylates casein and phosvitin but not histone and protamine using either ATP or GTP, co-fractionates with coated vesicles as assayed by gel filtration, electrophoresis, and sedimentation. The enzyme can be extracted with 0.5 M Tris HCl or 1 M NaCl, and can be separated from the pp50 kinase as well as the other major coat proteins. We identified this enzyme as casein kinase II based on physical and catalytic properties and by comparative studies with casein kinase II isolated from brain cytosol. It has a Stokes radius of 4.5 nm, a catalytic moiety of approximately 45 kDa, and labels a polypeptide of 26 kDa when the pure enzyme is assayed for autophosphorylation. Its activity is inhibited by heparin and not affected by cAMP, phospholipids, or calmodulin. This protein kinase preferentially phosphorylates clathrin beta-light chain. The phosphorylation is markedly stimulated by polylysine and inhibited by heparin. Isolated beta-light chain as well as beta-light chain in triskelions or in intact coated vesicles is phosphorylated. All of the phosphate (0.86 mol of Pi/mol of clathrin beta-light chain) is incorporated into phosphoserine. PMID- 2874132 TI - Factor V is a substrate for the transamidase factor XIIIa. AB - Coagulation Factor V (Mr = 330,000), upon cleavage by thrombin, produces Factor Va, which is composed of two subunits with Mr values of 94,000 and 74,000, along with two activation fragments possessing no known function. Studies were undertaken to assess the ability of the transamidase Factor XIIIa to covalently incorporate the lysine analogs [3H]putrescine and dansylcadaverine into the thrombin-cleaved (activated) and unactivated forms of human and bovine Factor V. The incorporation of either probe into thrombin-activated Factor V proceeded at an initial rate approximately twice that for unactivated Factor V. The extent of the incorporation of [3H]putrescine or dansylcadaverine into activated or unactivated human Factor V was identical; 4 mol of either probe per mol of Factor V. In the case of bovine Factor V, however, while 4 mol of probe were bound per mol of the unactivated pro-cofactor, 5 mol of either lysine analog were covalently linked to 1 mol of thrombin-cleaved Factor V. Polyacrylamide gel fluorography, immunoaffinity chromatography, and immunoprecipitation identified the largest activation fragment of human Factor V (Mr = 150,000) and bovine Factor V (Mr = 120,000) to contain the sites of incorporation of the covalently bound probes. High molecular weight, apparently covalent polymers of Factor V were produced by the action of Factor XIIIa on activated and unactivated human or bovine Factor V. The absence of either probe in the reaction mixtures did not appear to allow an enhancement of protein polymerization. PMID- 2874133 TI - Participation of three distinct active states of chloroplast ATPase complex CF0 X CF1 in the activation by light and dithiothreitol. AB - Chloroplast ATPase complex (CF0 X CF1) in thylakoids is activated by illumination in the presence or absence of dithiothreitol or by incubation with both dithiothreitol and Pi in the post-illumination dark. The activation by dithiothreitol and Pi is inhibited by ADP and decreases with increasing time interval between the end of illumination and the addition of dithiothreitol and Pi. The dithiothreitol/Pi-activated ATP hydrolysis is highly sensitive to pH. The ATP hydrolysis activated by illumination in the presence of dithiothreitol decreases its sensitivity to stimulation by NH4Cl and increases its sensitivity to pH, with increasing time interval between the end of illumination and the addition of ATP. Its pH dependence approaches that of the dithiothreitol/Pi activated ATP hydrolysis. These results suggest that in the post-illumination dark, the light/dithiothreitol-activated CFo X CF1 converts its state from the one (E2) which is sensitive to an uncoupler and relatively insensitive to pH to the one (E2i) which is insensitive to an uncoupler and highly sensitive to pH. In the post-illumination dark, the presence of both dithiothreitol and Pi brings about the activation of CFo X CF1 to E2i. PMID- 2874134 TI - Direct measurement of the electrogenicity of the H+-ATPase from thermophilic bacterium PS3 reconstituted in planar phospholipid bilayers. AB - The proton-translocating ATPase of the thermophilic bacterium PS3 was incorporated into a planar phospholipid bilayer, and its electrogenicity was directly demonstrated. The enzyme (TF0F1) consists of a catalytic portion, F1, and a membrane-integrated portion, Fo. A short-circuit current of up to 1 nA/cm2 was generated upon the addition of ATP, and the direction of the current indicated the flow of positive charges from the TF1 side to the TF0 side. The generation of the electric current was progressively suppressed by the presence of an inhibitor of TF1 such as NaN3 or adenyl-5'-yl imidodiphosphate. An open circuit membrane potential of 40-120 mV was also demonstrated (more negative on the TF1 side), which was inhibited by NaN3. Furthermore, an applied voltage of 180 mV (TF1 side negative) was sufficient to prevent the generation of electric current dependent on ATP hydrolysis, which indicated that the electrogenicity of TF0F1 is some 180 mV under the conditions studied. From these results it was tentatively concluded that the number of protons transported across the bilayer/mol of ATP is more than 3. PMID- 2874135 TI - Cellular distribution of type I and type II receptors for transforming growth factor-beta. AB - Affinity labeling of target cells for transforming growth factor-beta (TGF beta) by cross-linking with 125I-TGF beta via disuccinimidyl suberate or by the photoreactive analogue 4-azidobenzoyl-125I-TGF beta has revealed the presence of multiple TGF beta receptor forms. Two distinct types of TGF beta receptors can be distinguished based on structural analysis of the 125I-TGF beta-labeled species by peptide mapping. Type I TGF beta receptors include the 280-kilodalton labeled receptor form previously found to be the subunit of a disulfide-linked TGF beta receptor complex. (Massague, J. (1985) J. Biol. Chem. 260, 7059-7066), as well as a 65-kDa labeled receptor form present in all cell lines examined, and a 130-140 kDa labeled receptor form detected only in 3T3-L1 cells. The 280-kDa form is the major TGF beta receptor species in most cell lines examined, but is apparently absent in rat skeletal muscle myoblasts. Type I TGF beta receptors bind TGF beta with an apparent Kd of 50-500 pM. Type II TGF beta receptors include an 85-kDa labeled receptor form present in all mammalian cells examined and a 110-kDa labeled receptor form present in chick embryo fibroblasts. Type II TGF beta receptors bind TGF beta with an apparent Kd of about 50 pM. Except for the 280 kDa type I TGF beta receptor form, none of the TGF beta receptor forms described here is found as part of a disulfide-linked receptor complex. All the TGF beta receptor forms described here behave as intrinsic membrane proteins exposed on the surface of intact cells. PMID- 2874136 TI - Genetic evidence for interaction between the a and b subunits of the F0 portion of the Escherichia coli proton translocating ATPase. AB - A mutation of the b subunit of the Escherichia coli proton translocating ATPase was previously described (Porter, A. C. G., Kumamoto, C., Aldape, K., and Simoni, R. D. (1985) J. Biol. Chem. 260, 8182-8187). This mutation, which causes substitution of aspartic acid for glycine at position 9 (basp9), results in loss of function of the ATPase complex. In this paper we describe the isolation and characterization of two mutations that partially suppress the effects of the basp9 alteration. The suppressor mutations cause amino acid substitutions at position 240 of the a subunit. Membranes derived from strains carrying a suppressor mutation and the basp9 mutation exhibited ATP-dependent proton translocating activity. PMID- 2874137 TI - Impaired proton conductivity resulting from mutations in the a subunit of F1F0 ATPase in Escherichia coli. AB - Mutations in the uncB gene which encodes the a subunit of F1F0-ATPase in Escherichia coli were isolated and characterized. Eight mutations caused premature polypeptide chain termination. Two mutations were single amino acid substitutions resulting in the replacements of serine 206 with leucine (ser-206-- -leu) and histidine 245 with tyrosine (his-245----tyr). The ser-206----leu mutation does not alter F1 binding and allows ATP driven membrane energization at a low level. Stripping of F1 from membranes containing the ser-206----leu mutation does not render the membranes permeable to protons indicating impaired proton conductivity. The his-245----tyr mutation also blocks Fo-mediated proton conduction but has normal F1 binding properties. F1 bound to membranes with both ser-206----leu and his-245----tyr mutant a subunits is sensitive to dicyclohexylcarbodiimide. Apparently, both missense mutations impair proton conduction without altering assembly of the F1F0-ATPase complex. The direct involvement of the a subunit in proton translocation is discussed. PMID- 2874138 TI - The purine nucleotide cycle and ammoniagenesis in rat kidney tubules. AB - The contribution of the purine nucleotide cycle to renal ammoniagenesis was examined in cortical tubule suspensions prepared from acidotic rats and incubated with [alpha-15N]glutamine, [15N]glutamate, or [15N]aspartate. Labeling of ammonia and adenine nucleotides was determined after enzymatic transformations designed to circumvent the technical problem that 15NH3 and H2O have the same nominal mass. Labeling of the adenine nucleotide was undetectable (less than 10%) even after 1 h of incubation. From the measured concentrations of adenine nucleotides and ammonia and the labeling of the ammonia, the flux through the purine nucleotide cycle was calculated to account for less than 1% of the deamination of alpha-amino groups from all three substrates. The glutamate dehydrogenase reaction is therefore the likely pathway for deamination. The rate of 15NH3 production from [alpha-15N]glutamine was two or three times greater than from added [15N]glutamate, indicating a preference for intracellularly generated glutamate. 15NH3 production from added [15N]aspartate was similar to and perhaps slightly greater than that from added [15N]glutamate. PMID- 2874139 TI - A single amino acid substitution in an ectopic alpha subunit of a human carcinoma choriogonadotropin. AB - Human choriogonadotropin [hCG] has two dissimilar noncovalently associated subunits, designated alpha and beta. An ectopically secreted hCG alpha subunit that fails to associate with the beta subunit and displays an anomalously high molecular weight on molecular sieve chromatography but not on sodium dodecyl sulfate-polyacrylamide gel electrophoresis has been sequenced. A single substitution of Glu56 by Ala56 has been found in the altered subunit. No evidence for conformational differences between normal and ectopic alpha could be found using circular dichroism or intrinsic fluorescence as measures of secondary and tertiary structure, respectively. Hydrophobicity profiles as determined by the method of Kyte and Doolittle (Kyte, J., and Doolittle, R. F. (1982) J. Mol. Biol. 157, 105-132) predicted, however, that the hydrophilic segment, Thr54-Ser55-Glu56 Ser57-Thr58, becomes an extension of the preceding hydrophobic segment when Glu56 is substituted with Ala. This solitary hemoglobin S-like mutation may lead to an altered tertiary structure, self dimerization, or an alteration in glycosylation that could be responsible for the ectopic alpha subunit's failure to associate with the beta subunit. PMID- 2874140 TI - Identification of four phosphorylation sites in the N-terminal region of tyrosine hydroxylase. AB - As reported previously [Vulliet et al. (1985) FEBS Lett. 182 335-339], tyrosine hydroxylase purified from rat pheochromocytoma is phosphorylated at an identical site (site A) by cyclic AMP-dependent protein kinase, the calmodulin-dependent multiprotein kinase and protein kinase C, while the calmodulin-dependent multiprotein kinase also phosphorylates another unique site (site C). Preparations of tyrosine hydroxylase purified from this source are also contaminated with traces of a fourth protein kinase which phosphorylates another unique site (site E). We have isolated tryptic peptides containing each of these sites and determined their amino acid sequences. By comparison of these data with the known cDNA sequence for rat tyrosine hydroxylase, we have been able to identify these sites as Ser-8 (site E), Ser-19 (site C), and Ser-40 (site A). In some preparations of tyrosine hydroxlyase, cyclic AMP-dependent protein kinase also phosphorylated a secondary site which was identified as ser-153. All of these phosphorylation sites are in the amino-terminal region, where there is no significant homology with the closely related enzyme, phenylalanine hydroxylase. Our data also establish that the initiator methionine is removed by post translational processing to leave pro-2 as the amino-terminus of the mature protein. The significance of these results for the mechanism of action of extracellular signals on catecholamine biosynthesis is discussed. PMID- 2874141 TI - Amino acid sequence of Escherichia coli glutamine synthetase deduced from the DNA nucleotide sequence. AB - Glutamine synthetase is encoded by the glnA gene of Escherichia coli and catalyzes the formation of glutamine from ATP, glutamate, and ammonia. A 1922 base pair fragment from a cDNA containing the glnA structural gene for E. coli glutamine synthetase has been sequenced. An open reading frame of 1404 base pairs encodes a protein of 468 amino acid residues with a calculated molecular weight of 51,814. With few exceptions, the amino acid sequence deduced from the DNA sequence agreed very well with the amino acid sequences of several peptides reported previously. The secondary structure predicted for the E. coli enzyme has approximately 36% of the residues in alpha-helices which is in agreement with calculations of approximately 39% based on optical rotatory dispersion data. Comparison of the amino acid sequences of glutamine synthetase from E. coli (468 amino acids) and Anabaena (473 amino acids) (Turner, N. E., Robinson, S. T., and Haselkorn, R. (1983) Nature 306, 337-342) indicates that 260 amino acids are identical and 80 are of the same type (polar or nonpolar) when aligned for maximum homology. Several homologous regions of these two enzymes exist, including the sites of adenylylation and oxidative modification, but the regulation of each enzyme is different. PMID- 2874142 TI - Topology and function of "stalk" proteins in the bovine mitochondrial H+-ATPase. AB - Proton translocating ATPases comprise a hydrophilic sector F1, a membrane sector F0, and, in the case of bovine mitochondria, a connecting "stalk" which is believed to contain the oligomycin sensitivity-conferring protein (OSCP) and coupling factor 6 (F6). The present study was undertaken to verify the accessibility of F6 and OSCP to trypsin and to examine the functional consequences of such treatment. Our data show that F1 binds equally to trypsin treated F0 and untreated F0, but the former complexes exhibit cold lability and only partial sensitivity to oligomycin. Furthermore, these complexes fail to exhibit ATP-driven proton translocation or ATP-32Pi exchange activity. Trypsinization of F0 does not, however, inhibit passive proton conductance through the membrane sector but actually enhances it. Immunological data indicate extensive degradation of OSCP under conditions where F6 proteolysis is insignificant. Intact H+-ATPase complexes are relatively resistant to both the structural and functional effects of trypsin. We conclude that OSCP is predominantly an extrinsic protein which is shielded by F1 in the native membrane. F6 may also be an extrinsic protein but is shielded from trypsinization by OSCP and/or other F0 polypeptides. The exposed, trypsin-sensitive segments of OSCP are not required for passive proton conductance through F0 but may be required for ATP-driven reactions. We propose that bovine mitochondrial OSCP is a functional analogue of subunit b in the Escherichia coli H+-ATPase. PMID- 2874143 TI - Characterization of an essential arginine residue in the plasma membrane H+ ATPase of Neurospora crassa. AB - Treatment of the plasma membrane H+-ATPase of Neurospora crassa with the arginine specific reagents phenylglyoxal or 2,3-butanedione at 30 degrees C, pH 7.0, leads to a marked inhibition of ATPase activity. MgATP, the physiological substrate of the enzyme, protects against inactivation. MgADP, a competitive inhibitor of ATPase activity with a measured Ki of 0.11 mM, also protects, yielding calculated KD values of 0.125 and 0.115 mM in the presence of phenylglyoxal and 2,3 butanedione, respectively. The excellent agreement between Ki and KD values makes it likely that MgADP exerts its protective effect by binding to the catalytic site of the enzyme. Loss of activity follows pseudo-first order kinetics with respect to phenylglyoxal and 2,3-butanedione concentration, and double log plots of pseudo-first order rate constants versus reagent concentration yield slopes of 0.999 (phenylglyoxal) and 0.885 (2,3-butanedione), suggesting that the modification of one reactive site/mol of H+-ATPase is sufficient for inactivation. This stoichiometry has been confirmed by direct measurements of the incorporation of [14C]phenylglyoxal. Taken together, the results support the notion that one arginine residue, either located at the catalytic site or shielded by a conformational change upon nucleotide binding, plays an essential role in Neurospora H+-ATPase activity. PMID- 2874144 TI - Isolation and identification of a cDNA clone of rat placental lactogen II. AB - The developing rat placenta expresses two placental lactogens at different stages of pregnancy: rat placental lactogen I from Days 11 to 13 of pregnancy and rat placental lactogen II (rPLII) from Day 12 to term. In this paper, we describe cDNA clones for rPLII, which have been isolated from a Day 18 rat placental cDNA library. The rPLII clones hybrid-select a mRNA which translates in vitro to a protein of 25,000 daltons. This protein is processed by dog pancreatic microsomes to a 22,000-dalton form, identical in size to rPLII isolated from pregnant rat serum. Both forms are precipitated by an anti-rPLII antiserum and an anti-ovine prolactin antiserum. The mRNA for rPLII is first expressed in Day 12 placenta and reaches a maximum at about Day 18 of pregnancy, in parallel with the appearance of the hormone in serum. Sequencing of the cDNA shows that, unlike human placental lactogen which is 85% homologous to human growth hormone at the amino acid level, rPLII is much more closely related to the prolactins. Thus, rPLII is 52% homologous to rat prolactin at the amino acid level, but only 34% related to rat growth hormone. This is the second placental lactogen to be fully characterized, and in the rat this hormone appears to have evolved by a route quite different from that which produced placental lactogen in humans. PMID- 2874145 TI - Alpha 1-adrenergic stimulation of arachidonic acid release and metabolism in a rat thyroid cell line. Mediation of cell replication by prostaglandin E2. AB - The rat thyroid cell line, FRTL-5, expresses an alpha 1-adrenergic receptor when exposed to thyrotropin. We have found that occupation of this alpha 1-adrenergic receptor by norepinephrine stimulated the release of [3H]arachidonic acid from prelabeled cells. Arachidonic acid was metabolized primarily to prostaglandin E2 and to much smaller amounts of 11-hydroxy-5,8,11,13-eicosatetraenoic acid, 15 hydroxy-5,8,11,13-eicosatetraenoic acid, prostaglandin D2, and thromboxane B2. Synthesis of all these metabolites was inhibited by the cyclooxygenase inhibitor indomethacin. When FRTL-5 cells were starved of thyrotropin for 24 h, norepinephrine nearly doubled [3H]thymidine uptake into DNA. Cyclooxygenase inhibitors inhibited norepinephrine-stimulated thymidine uptake by 60-70%. Of several arachidonic acid metabolites tested, none was able to stimulate thymidine uptake directly in the presence of indomethacin. Prostaglandin E2, however, was able to restore [3H]thymidine uptake when added together with norepinephrine in the presence of indomethacin. Thus, occupation of an alpha 1-adrenergic receptor in a functional rat thyroid cell line leads to arachidonic acid release. Subsequent metabolism of the arachidonic acid by the cyclooxygenase pathway leads to synthesis of prostaglandin E2, which mediates a norepinephrine-stimulated activity related to cell replication. PMID- 2874146 TI - Carcinogenicity studies of some analogs of the carcinogen methapyrilene in F344 rats. AB - Four antihistaminic drugs similar in structure to the rat liver carcinogen methapyrilene were administered to comparable groups of male and female F344 rats in their drinking water for most of their lifetime (80-108 weeks). The concentrations were 0.1% or 0.05% and the total doses received by the animals were comparable with that of methapyrilene which induced 100% incidence of liver neoplasms. No increase in incidence of liver neoplasms was observed after treatment with any of the four compounds, thenyldiamine, chlorothen, methafurylene, or methaphenilene, although each differed structurally from methapyrilene only in one atom or one position of substitution. There were a few animals with neoplasms not usually found in untreated F344 rats, but none of these was found in statistically significant numbers. These results suggest that none of the four analogs of methapyrilene was carcinogenic under the conditions of this study, and that the property of inducing liver neoplasms in rats was confined to the intact methapyrilene molecule. PMID- 2874147 TI - Internalization of transforming growth factor-beta and its receptor in BALB/c 3T3 fibroblasts. AB - The fate of 125I-labeled transforming growth factor-beta (125I-TGF beta) after binding to its cells surface receptor has been investigated in BALB/c 3T3 mouse fibroblasts. Binding of 125I-TGF beta to cellular receptors at 4 degrees C is pH sensitive, being markedly decreased at pH less than 6. Most (approximately 90%) of the 125I-TGF beta bound to cells at 4 degrees C can be removed by a brief treatment with acidic medium but is converted into an acid-resistant state rapidly after shifting the cells to 37 degrees C. Cell-bound 125I-TGF beta is degraded at 37 degrees C and the degradation products are released into the medium. The lysosomotropic bases chloroquine, methylamine, and ammonium and the carboxylic ionophore monensin inhibit the degradation and release of 125I-TGF beta from the cells. Cells allowed to accumulate 125I-TGF beta intracellularly by the action of chloroquine or monensin were treated with the bifunctional agent disuccinimidyl suberate in the presence of detergent Triton X-100; this treatment caused the cross-linking of internalized 125I-TGF beta with the 280-kilodalton TGF beta receptor component. Under conditions in which sustained binding and degradation of saturating 125I-TGF beta concentrations occurs, there is no marked decrease in the binding capacity of the cells even when protein synthesis is blocked with cycloheximide. These results indicate that after TGF beta binding the TGF beta:receptor complex becomes rapidly internalized and that TGF beta is directed towards lysosomes where it is degraded and released. However, the cell surface is replenished with TGF beta receptors recycled after internalization or supplied by a large intracellular pool. PMID- 2874148 TI - In vivo biosynthesis of clathrin and other coated vesicle proteins from rat liver. AB - A biosynthetic study of rat liver coated vesicle (CV) proteins was undertaken by using in vivo labeling with L-[35S]methionine. CVs were isolated and purified by using standard procedures and characterized by electron microscopy, sedimentation, and sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by fluorography, or by gel slicing and liquid scintillation counting. After 5 1/2 min of labeling (the earliest time examined), incorporation of radioactive clathrin heavy-chain (180-kD (kilodalton] subunits as well as a 90-kD CV-associated protein into purified CVs was demonstrated. The level of labeled 180-kD clathrin in coated vesicles increased rapidly during the first 2 hr of labeling and then continued to rise at a slower rate between 4 and 16 hr. This slow accumulation of labeled clathrin heavy chains in the CV pool may reflect early compartmental sequestration of a fraction of newly synthesized clathrin with delayed assembly into free CVs. By 16 hr of labeling, clathrin 180-kD chains and the 90-kD CV-associated protein accounted for approximately 48 and 26%, respectively, of the radioactivity in all CV proteins. Two proteins of MWa 68 kD and 53 kD showed marked declines in cpm/unit protein between 30 min and 4 hr, raising the possibility that these species may be transferred out of CVs during or after transport without loss of the other CV proteins. The possibility is also raised that clathrin heavy chains may be recycled during CV formation. Possible heterogeneity within individual CV preparations with respect to protein composition and derivation from both plasma membrane and Golgi regions are proposed. PMID- 2874149 TI - High-performance liquid chromatography and diode-array detection for the identification of peptides containing aromatic amino acids in studies of endorphin-degrading activity in human cerebrospinal fluid. AB - Diode-array UV detection has been adapted for analysis of opioid peptides and their metabolic fragments differing in aromatic amino acid content. In combination with high-performance liquid chromatography, the technique allowed a direct and rapid discrimination between peptides containing phenylalanine, tryptophan and tyrosine, or a combination of these residues. Enkephalin fragments with either tyrosine or phenylalanine, or both, were identified after digestion of the pentapeptide with proteolytic activity recovered from human cerebrospinal fluid. The N-terminal tyrosine-containing fragment of dynorphin A was identified after hydrolysis of the peptide by a cerebrospinal fluid endopeptidase. The study was extended to the analysis of some non-opioid peptides. The Tyr1 analogue of delta-sleep-inducing peptide was easily distinguished from the authentic compound with a tryptophan at the N-terminus. Results indicated that the technique was useful for discriminating between dipeptides differing in aromatic residues that were unresolved by high-performance liquid chromatography. PMID- 2874150 TI - Simultaneous determination of 2-(p-chlorophenyl)pyrazolo[4,3-c] quinoline-3(5H) one and its 6-, 7- and 8-hydroxy metabolites in plasma, urine and bile by high performance liquid chromatography. PMID- 2874151 TI - Underivatized measurement of bromazepam by gas chromatography-electron-capture detection with application to single-dose pharmacokinetics. PMID- 2874152 TI - Simple and sensitive method for the determination of clobazam, clonazepam and nitrazepam in human serum by high-performance liquid chromatography. PMID- 2874153 TI - The influence of graded hyperglycemia with and without physiological hyperinsulinemia on forearm glucose uptake and other metabolic responses in man. AB - We studied the influence of hyperglycemia on glucose homeostasis in man by determining the effect of graded hyperglycemia on peripheral glucose uptake and systemic metabolism in the presence of basal and increased serum insulin concentrations in 10 normal men. This was achieved by the simultaneous application of forearm and clamp techniques (euglycemic and hyperglycemic) during the combined iv infusion of somatostatin, glucagon, and insulin. While mean (+/- SE) basal serum insulin levels (14 +/- 2 microU/ml) were maintained, the elevation of fasting arterial glucose concentrations (90 +/- 1 mg/dl) to 146 +/- 1 and 202 +/- 1 mg/dl (each for 120 min) increased forearm glucose uptake (FGU) only modestly from 0.06 +/- 0.01 to 0.15 +/- 0.02 and then to 0.24 +/- 0.03 mg/100 ml forearm X min, respectively. During physiological hyperinsulinemia (47 +/- 3 microU/ml), the influence of similar graded hyperglycemia on FGU was considerably enhanced. At plasma glucose concentrations of 90 +/- 1, 139 +/- 1, and 206 +/- 1 mg/dl, FGU rose to 0.33 +/- 0.05, 0.59 +/- 0.07, and 0.83 +/- 0.12 mg/100 ml forearm X min, respectively. The glucose infusion rate required to maintain the glucose clamp with basal insulin levels was 1.08 +/- 0.20 and 2.67 +/- 0.39 mg/kg X min at glucose concentrations of 146 +/- 1 and 202 +/- 1 mg/dl, respectively. During physiological hyperinsulinemia, however, the glucose infusion rate required was 4.15 +/- 0.39, 9.45 +/- 1.05, and 12.70 +/- 0.81 mg/kg X min at glucose levels of 90 +/- 1, 139 +/- 1, and 206 +/- 1 mg/dl, respectively. Lactate concentrations rose significantly during hyperglycemia, but the rise in the presence of increased insulin concentrations (from 0.72 +/- 0.06 to 1.31 +/- 0.11 mmol/liter; P less than 0.001) considerably exceeded the increment (from 0.74 +/- 0.05 to 0.92 +/- 0.03 mmol/liter) with basal insulin levels. While both FFA and glycerol concentrations were immediately reduced by euglycemic hyperinsulinemia, the fall in FFA during hyperglycemia in the presence of basal insulin levels preceded the decrease in glycerol concentrations by 45 min. Forearm oxygen consumption did not change throughout the study.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2874154 TI - Thyroid growth immunoglobulins in large multinodular endemic goiters: effect of iodized oil. AB - Iodized oil (IO) was administered to 10 goitrous patients recently emigrated to Sao Paulo (SP) from iodine deficiency areas and to 42 goitrous patients from 2 Brazilian chronic iodine deficiency regions, Loreto and Luziania (L). Thyroid growth-promoting immunoglobulin G (IgG) thyroid-stimulating antibody, serum thyroglobulin (Tg), TSH, and thyroid hormones were measured before and 1 yr after IO administration. In all patients there was a remarkable reduction of gland mass associated with a significant decrease (P less than 0.01) in both basal serum Tg and peak Tg levels after bovine TSH administration. The mean percent Tg increase after bovine TSH treatment was reduced to 82% above basal levels compared with 224% before IO. Mean serum TSH levels, elevated only in the L group [7.3 +/- 11 (+/- SD) microU/ml] decreased to the normal range after IO (2.5 +/- 2.1 microU/ml). Serum T3 and T4 concentrations did not change greatly. Tests for microsomal antibodies were negative before and after IO. IgG concentrates of serum obtained before and after IO were tested for their ability to stimulate incorporation of [3H]thymidine into DNA or to increase intracellular generation of cAMP in FRTL-5 cells. Thymidine incorporation activity was found in 8 of 10 patients from SP [316 +/- 37% (+/- SEM); range, 140-480%] and 25 of 42 patients in the L group (mean, 206 +/- 14; range, 120-500%) before IO. Stimulation of thymidine incorporation reflected true growth-promoting activity, as confirmed by experiments measuring cell number, was not accounted for by TSH in the preparation, and reflected IgG action because it was abolished by absorption with antihuman IgG. IgG from only 1 patient in group SP and 4 patients in group L stimulated intracellular production of cAMP in FRTL-5 cells. All patients except 1 in both groups had no IgG stimulation (less than 120%) of growth-promoting activity 1 yr after IO treatment. There was a significant positive correlation between thyroid growth-promoting activity and serum Tg concentrations (r = 0.58; P less than 0.001), but no significant correlation was found with other parameters (TSH, T4, and T3). We conclude that growth-promoting IgGs lacking ability to stimulate cAMP production may play a role in the large multinodular goiters due to chronic iodine deficiency. PMID- 2874155 TI - Physician extender services in family planning agencies: issues in Medicaid reimbursement. PMID- 2874157 TI - Pharmacotherapy of psychiatric emergencies. AB - The psychiatric emergency service has become a major provider of psychiatric care over the past decade. Concomitant with this growth has been an emphasis on pharmacological treatment. While rapid tranquilization is the best known and most frequently used intervention, a growing diagnostic awareness has led to a variety of other chemotherapeutic approaches. The current reviews of pharmacologic intervention in the psychiatric emergency service do not detail the variability of treatment approaches or examine alternative treatment approaches. The goal of this article is to critically review current pharmacologic treatments and address areas in which there is no consensus in treatment approach. From this review the authors suggest guidelines for pharmacotherapy of psychiatric emergencies. The authors discuss rapid tranquilization, the treatment of alcohol and drug intoxication and withdrawal, and anxiety disorders. PMID- 2874156 TI - Binding and covalent cross-linking of purified von Willebrand factor to native monomeric collagen. AB - We have analyzed the interaction of the adhesive glycoprotein, von Willebrand factor (vWF), with native monomeric collagen monolayers by adsorbing acid soluble Types I and III collagen derived from calf skin to polystyrene microtiter wells and incubating the wells with purified human 125I-vWF. The binding of 125I-vWF was saturable, reversible, specific, and was abolished by heat denaturation of the collagen monomers. Binding was half-maximal at 5 micrograms/ml, and, at saturation, 7.5 ng 125I-vWF were bound to each microgram of immobilized collagen. 125I-vWF did not bind to wells coated with other extracellular matrix or plasma proteins such as fibronectin, fibrinogen, gelatin, or the q subunit of the first component of complement (C1q). In addition, bound 125I-vWF could not be displaced from collagen by the addition of either fibronectin or fibrinogen. After incubation with Factor XIIIa, plasma transglutaminase, 125I-vWF bound to collagen could no longer be displaced by vWF, which suggests covalent cross-linking of vWF to collagen monomers. Factor XIIIa-dependent covalent cross-linking of vWF to collagen, but not to fibronectin or laminin, was also demonstrated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. PMID- 2874158 TI - Carbamazepine in dementia. AB - Dementia is an ailment that is becoming a major management problem. The presentations of dementias vary depending upon the site of lesions and their severity. Different medications have been tried to relieve some of the more common symptoms associated with the dementias. This report shows the use of carbamazepine as one medication that could be utilized for the resolution of mania-like symptoms that sometimes occur in this condition. PMID- 2874159 TI - Distribution of dynorphin and enkephalin peptides in the rat brain. AB - The neuroanatomical distribution of dynorphin B-like immunoreactivity (DYN-B) was studied in the adult male and female albino rat. The distribution of DYN B in colchicine- and noncolchicine-treated animals was also compared to that of another opioid peptide derived from the prodynorphin precursor dynorphin A (1-8) (DYN 1-8), and an opioid peptide derived from the proenkephalin precursor met enkephalin-arg-gly-leu (MERGL). DYN B cell bodies were present in nonpyramidal cells of neo- and allocortices, medium-sized cells of the caudate-putamen, nucleus accumbens, lateral part of the central nucleus of the amygdala, bed nucleus of the stria terminalis, preoptic area, and in sectors of nearly every hypothalamic nucleus and area, medial pretectal area, and nucleus of the optic tract, periaqueductal gray, raphe nuclei, cuneiform nucleus, sagulum, retrorubral nucleus, peripeduncular nucleus, lateral terminal nucleus, pedunculopontine nucleus, mesencephalic trigeminal nucleus, parabigeminal nucleus, dorsal nucleus of the lateral lemniscus, lateral superior olivary nucleus, superior paraolivary nucleus, medial superior olivary nucleus, ventral nucleus of the trapezoid body, lateral dorsal tegmental nucleus, accessory trigeminal nucleus, solitary nucleus, nucleus ambiguus, paratrigeminal nucleus, area postrema, lateral reticular nucleus, and ventrolateral region of the reticular formation. Fiber systems are present that conform to many of the known output systems of these nuclei, including major descending pathways (e.g., striatonigral, striatopallidal, reticulospinal, hypothalamospinal pathways), short projection systems (e.g., mossy fibers in hippocampus, hypothalamo-hypophyseal pathways), and local circuit pathways (e.g., in cortex, hypothalamus). The distribution of MERGL was, with a few notable exceptions, in the same nuclei as DYN B. From these neuroanatomical data, it appears that the dynorphin and enkephalin peptides are strategically located in brain regions that regulate extrapyramidal motor function, cardiovascular and water balance systems, eating, sensory processing, and pain perception. PMID- 2874160 TI - Immunohistochemical morphometry of pancreatic endocrine cells in diabetic, normoglycaemic glucose-intolerant and normal cats. AB - The anatomical distribution and volume fractions of pancreatic A cells (glucagon), B cells (insulin) and D cells (somatostatin) were evaluated by an immunoperoxidase technique in 6 diabetic cats, 6 normoglycaemic glucose intolerant cats and 6 normal control cats. Islets lacking A cells were observed in some sections from the right lobe of the pancreas which correlated with a significantly lower A cell volume fraction in the right pancreatic lobe. Endocrine cell volume fractions in normoglycaemic glucose-intolerant cats were not significantly different from controls. Thus, a reduction in B cell volume fraction was not necessary for the occurrence of impaired glucose tolerance in these cats. However, the reduction of B cell volume fraction in the 2 normoglycaemic glucose-intolerant cats with insular amyloidosis may in part explain the more severely impaired glucose tolerance previously observed in these cats. Insular amyloidosis in our feline diabetics, as in human type II diabetics, was associated with a significant decrease in A and B cell volume fractions. In both human type II and feline diabetes mellitus, however, the reduction in B cell mass does not appear sufficient alone to lead to diabetes mellitus. Therefore, amyloid replacement of functional endocrine cells does not appear to be the primary diabetogenic event in feline diabetes mellitus, but may contribute to progression of the condition due to loss of functional B cell reserves. We thus postulate that a B cell defect precedes deposition of islet amyloid and that these amyloid deposits may thus provide an important biochemical clue to specific B cell derangements occurring in adult-onset diabetics. PMID- 2874161 TI - Mycotic right coronary artery aneurysm: CT and MR diagnosis. AB - A clostridial mycotic aneurysm of the right coronary artery was diagnosed by the use of multiple imaging modalities including gated magnetic resonance imaging. Percutaneous drainage was performed as a palliative measure in hope of avoiding repeat sternotomy. PMID- 2874162 TI - Aortic pseudoaneurysm complicating Takayasu disease: CT appearance. AB - The CT findings of a patient with Takayasu arteritis and an ascending aortic pseudoaneurysm are presented. Computed tomography demonstrated the nature, location, and extent of the aortic lesion and revealed the ominous finding of a related large hematoma indicating prior aortic rupture. PMID- 2874163 TI - A simple method for the assay of Bordetella pertussis adenylate cyclase employing 31P nuclear magnetic resonance spectroscopy. AB - A simple method for the simultaneous assay of both substrate utilization and product formation by Bordetella pertussis adenylate cyclase has been developed. This method involves measurement of ATP remaining in the reaction mixture and cyclic 3',5'-AMP (cAMP) formation by 31p-NMR spectroscopy. No separation of the nucleotides is required. The measurement of the rate of cAMP formation compared very well with other methods that require separation of product from the substrate. With this method it has been possible to show calmodulin activation of B. pertussis adenylate cyclase and to demonstrate an inhibition of calmodulin activation by melittin. The inhibition of calmodulin-activated adenylate cyclase by melittin is not permanent and can be overcome by long-term incubation. PMID- 2874164 TI - Actinomyces adsorption mediated by type-1 fimbriae. AB - Monospecific antibody against the type-1 fimbriae of Actinomyces viscosus T14V reacted with 12 strains of A. viscosus (serotype 2), 12 strains of A. naeslundii (serotype 2 or serotype 3), but not with 11 serotype 1 strains of A. naeslundii. All strains positive for the type-1 fimbrial antigen adsorbed strongly to saliva treated hydroxyapatite, and in many instances (18 of 24 strains) this interaction was inhibited by the monospecific antibody. These findings strongly suggest that only those strains of actinomyces which possess type-1 fimbriae adhere to the tooth surfaces, and that these fimbriae constitute the principal adhesin involved in this interaction. PMID- 2874165 TI - The Nursing Minimum Data Set Conference: executive summary. PMID- 2874166 TI - Fixation of osseous fragments in the foot. PMID- 2874167 TI - The effect of acid and bethanechol stimulation in patients with symptomatic hypertensive peristaltic (nutcracker) esophagus. Evidence that this disorder may be a precursor of diffuse esophageal spasm. AB - The hypertensive peristaltic (nutcracker) esophagus represents a motility disorder characterized clinically by squeezing retrosternal chest pain and manometrically by high amplitude esophageal peristaltic contractions. This study was designed to examine whether the nutcracker esophagus is: (a) a distinct entity, (b) a member of the spectrum of primary esophageal dysmotilities (e.g., diffuse esophageal spasm and achalasia), or (c) is secondary to reflux-induced acid sensitivity. Thirteen patients with a nutcracker esophagus by baseline manometry were subsequently studied after acid perfusion and bethanechol stimulation (0.08 mg/kg). Records were analyzed for symptomatic response and motility changes. Eight of 13 (62%) experienced chest pain during acid perfusion, but none had significant motility changes documented during this period. After bethanechol injection, chest pain occurred in six of 12 (50%) patients; two had burning pain and in the other four (33%) their squeezing chest pain was reproduced. Changes in the motility tracing with evidence of disordered motility suggestive of diffuse esophageal spasm were seen after bethanechol in seven of the 12 tracings analyzed (58%), including all six patients who developed chest pain. We conclude that patients with nutcracker esophagus on baseline manometry may develop motility patterns consistent with diffuse esophageal spasm after provocation with bethanechol. We take this to suggest that the nutcracker esophagus is part of the continuum of primary motility disorders and may actually be a precursor of diffuse esophageal spasm. PMID- 2874168 TI - A critical review of current medical therapy for gastroesophageal reflux disease. AB - Gastroesophageal reflux (GER) disease is a common, multifactorial medical condition that may be difficult to treat. Simple lifestyle modifications decrease reflux episodes and should serve as the cornerstone for medical therapy. Antacids or alginic acid may be helpful in mild disease but recent studies suggest they may be no better than placebo. Metoclopramide improves symptomatic GER disease but side effects are a major limiting factor. Only bethanechol and the histamine H2 antagonists have been conclusively shown to improve esophagitis significantly. Therefore, more severe disease is currently best treated with a histamine H2 antagonist alone or in combination with bethanechol. The treatment of GER complications and maintenance therapy have only been recently addressed in clinical trials, but again the histamine H2 antagonists may have a useful role. Five to 10% of patients may require antireflux surgery, but the competency of the repair appears to deteriorate with time. Future clinical trials need to address specific areas of difficulty including entry criteria, test of efficacy, study duration, and usefulness of combination drug therapy. PMID- 2874169 TI - Future medical therapy of reflux esophagitis. AB - In recent years, many new systemic medications have been developed as potential therapies for the patient with chronic GER and esophagitis. Despite these therapeutic advances, large numbers of GER patients continue to have chronic symptoms or unresolved complications. To some degree, this may relate to uncertainties regarding the pathogenesis of GER and its complications; i.e., is it primarily due to acid/pepsin injury or to primary motility disorders in the esophagus. Many new therapies are currently being developed, particularly those with the potential ability to enhance esophageal contractions--the prokinetic drugs. The main potential therapies of GER are discussed, including possible new acid suppression therapies, new anticholinergic drugs, new prokinetic drugs, and medications that might enhance the mucosal barrier. In addition, the more complex questions of effectiveness of chronic medical versus surgical therapy, and the use of combined medical therapies, are discussed. PMID- 2874170 TI - Tardive dyskinesia: barriers to the professional recognition of an iatrogenic disease. PMID- 2874171 TI - Concerning materials for gamma-glutamyl transpeptidase histochemistry. PMID- 2874172 TI - Yellow fever in Swansea, 1865. AB - A cargo of copper ore from Cuba was discharged at Swansea in mid-September 1865, during a spell of exceptionally hot weather. A small number of mosquitoes infected with the yellow fever virus, disembarking at the same time, established an epidemic of yellow fever in the town. In the next 25 days, at least 27 inhabitants were infected and 15 of them died. The quality of contemporary observation and recording has encouraged a re-examination of the events in the light of knowledge unavailable at the time. It cannot be assumed that the episode will not be repeated. PMID- 2874173 TI - Large outbreaks of Clostridium perfringens food poisoning associated with the consumption of boiled salmon. AB - Five large outbreaks of food poisoning are described in which clinical, epidemiological or laboratory data indicated Clostridium perfringens as the causative organism. The foodstuff common to all incidents was boiled salmon served cold as an hors d 'oeuvre. In all cases the fish had been subject to a long period of cooling or storage between boiling and consumption. It is thought that multiplication of the organism occurred during this time. Recommendations are made for the avoidance of further similar incidents. PMID- 2874174 TI - The effect of prolonged administration of CGS 10078B on systemic and regional haemodynamics in normotensive and spontaneously hypertensive rats. AB - The effects of 3 weeks treatment with CGS 10078B (30 mg/kg orally) on systemic and regional haemodynamics and cardiac mass were studied in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. The significant decrease in mean arterial pressure (MAP) (174 +/- 3 versus 156 +/- 4 mmHg, P less than 0.002) in SHR was associated with a significantly slower heart rate. No significant alteration in systemic haemodynamics was observed in WKY rats. The reduced MAP in SHR was related to the preserved blood flow to the vital organs, and therefore reduced renal and cerebrovascular resistances. Left ventricular mass index was reduced in both rat strains of treated animals. Therefore, the reduced MAP and heart rate in the SHR without haemodynamic changes in the WKY indicates that CGS 10078B was an effective antihypertensive agent that decreased cardiac mass in rats through mechanisms that may be dissociated from their haemodynamic effects. PMID- 2874176 TI - 1986 guidelines for the treatment of mild hypertension: memorandum from a WHO/ISH meeting. AB - The present guidelines were endorsed by the participants at the Fourth Mild Hypertension Conference, held at Konigstein, Federal Republic of Germany on 4-7 December 1985. They include the definition of mild hypertension, and describe blood pressure measurement, factors influencing the decision to begin treatment, methods of treatment, and follow-up. These guidelines are a revision of those produced in 1982; they are based on the best available scientific evidence, and will be updated in the future to keep abreast of further developments in this field. PMID- 2874175 TI - Cerebral blood flow and antihypertensive treatment with enalapril. AB - The intravenous 133Xenon method was used to measure regional cerebral blood flow (rCBF) in 20 patients with moderate hypertension. Regional cerebral blood flow under pretreatment, in the placebo period and after 8 weeks of enalapril treatment were compared. The rCBF values [(F1), and initial slope, (IS)] showed no statistical difference during the three periods in spite of significantly higher blood pressure values in the placebo period. It is concluded, that with enalapril good blood pressure control is achieved without any adverse effect on rCBF. PMID- 2874177 TI - Immunoregulatory activity of human bone marrow. Identification of suppressor cells possessing OKM1, SSEA-1, and HNK-1 antigens. AB - Human bone marrow contains natural regulatory cells capable of suppressing the in vitro primary IgM response of normal tonsillar cells. The suppression is mediated by non-T cells possessing Fc receptors, OKM1, SSEA-1, and HNK-1 antigens on their surface. The suppression was abrogated by treatment of bone marrow cells (BMC) with anti-HNK-1 or anti-SSEA-1 antisera and complement. Furthermore, BMC depleted of HNK-1+ cells could respond in a primary in vitro antibody response when provided with accessory T cells and macrophages from tonsillar cells. Our findings support the idea that HNK-1+ and HNK-1- BMC populations act antagonistically in the regulation of antibody synthesis. Further, the finding of HNK-1+, SSEA-1+, and OKM1+ suppressor cells in human bone marrow may represent a precursor phenotype of mature natural killer cells with potent immunoregulatory activity. PMID- 2874178 TI - Epidemiological studies on hemorrhagic fever with renal syndrome in China. AB - Hemorrhagic fever with renal syndrome (HFRS) has been reported from greater than 20 provinces in China. The number of reported cases has increased markedly in recent years and surpassed 80,000 human cases in 1983. All of the cases reported before 1981 were from rural areas and were attributed to Apodemus rats. In 1981, outbreaks of cases associated with house rats were first reported. Cases associated with Apodemus agrarius were more severe than those associated with the house rat Rattus norvegicus. The rate of inapparent infection in the rural population of areas endemic for Apodemus-associated disease was lower than that of Rattus-associated urban disease. After the onset of the disease, IgG antibody levels increase rapidly, peak after one week, and persist for as long as 25 years. Lung tissues from 16 species of rodent, from two species of sorex, and from cats and weasels in the epidemic areas have been found to carry antigen. A. agrarius, Apodemus peninsulae, and R. norvegicus serve as the main reservoirs of HFRS in rural areas, forest areas, and urban areas, respectively. PMID- 2874179 TI - Influence of trimethoprim and sulfamethoxazole on the synthesis, expression, and function of type 1 fimbriae of Escherichia coli. AB - We investigated the effects of low levels of sulfamethoxazole and trimethoprim on biosynthesis, expression at the cell surface, and hemagglutinating activity of type 1 fimbriae from a urinary tract isolate of Escherichia coli. The mannose sensitive hemagglutination of E. coli was reduced after growth in either of the antimicrobial agents. Moreover, trimethoprim affected antigenic fimbrial expression at the bacterial cell surface. Fimbrial subunit synthesis, as detected in lysates of solubilized whole bacteria, was inhibited in bacteria grown with one-half the minimum inhibitory concentration (MIC) or trimethoprim. Organisms grown in low doses of trimethoprim and sulfamethoxazole (one-thirty-second the MIC each) together exhibited marked reduction of fimbrial synthesis, expression, and hemagglutinating activity. Neither agent induced any detectable effect when used alone at the same concentrations. These results demonstrate that the synergistic activity of these drugs at concentrations below the MIC influence the synthesis, expression, and adhesive properties of type 1 fimbriae. PMID- 2874180 TI - [Echocardiographic manifestations of nonrheumatic aortic regurgitation]. AB - Recently, the frequency of nonrheumatic aortic regurgitation (AR) has apparently increased, accompanied by a decrease in frequency of rheumatic fever. The purpose of the present study was to ascertain the echocardiographic features of nonrheumatic AR. We had 24 surgically- or autopsy-proven cases of nonrheumatic AR admitted during a two year period. These were 10 cases of infective endocarditis (IE), five with ventricular septal defect of type I, three with syphilis, and two with prosthetic valve malfunctions, and the remainder five were difficult to diagnose clinically. These five were three men and two women, whose ages ranged from 40 to 67 years and averaged 50 years, and their final diagnoses were annulo aortic ectasia (AAE), Behcet's disease, and the aortitis syndrome (Takayasu's arteritis), and two other cases were of unknown etiology. The echocardiographic manifestations were compared with the operative, autopsy, and pathological findings. Echocardiographically, there were few or no increased intensities of aortic valvular echoes, and aortic roots had a tendency to dilate, leading to the failure of coaptation of valve leaflets, for a relative lack of valvular surface area to cross-sectional area of the aortic ring. Three of the five had flail aortic valves and three had associated MVP. Three were diagnosed as floppy aortic valves at the time of surgery. Excised valves revealed little hyperplasia or sclerosis grossly. Fibrinoid necrosis or mucoid degeneration were noted by light microscopy. Some specimens of aortic walls also revealed cystic medial necrosis or disruption of elastic fibers. All these findings were based on degenerative processes of connective tissue, and not on inflammatory processes. These pathological findings and the coexistence of mitral valve prolapse (MVP), which were not regarded as coincidental, suggest that connective tissue fragility- congenital or acquired--may play an important role in the genesis of nonrheumatic AR. PMID- 2874181 TI - [Bradykinin receptor and the mechanism of the onset of labor]. AB - Bradykinin (BK) receptor of uterus and chorionic membrane were studied by radioreceptor assay to clarify the role of BK as theta an agent contracting uterine muscle. Basic examination revealed that incubation at 0 degrees C for 45 minutes with [3H] BK in buffer containing 5mM Mg++ was the most suitable condition for receptor-BK binding. BK receptor assay of several kinds of tissue such as pregnant rat uterus, human chorionic membrane, and placenta was done and the following results were obtained. Specific BK receptor existed in human chorionic membrane and in rat uterus. Ultracentrifugation revealed that it was on the plasma membrane (145 f mole./mg protein: The highest binding in the pellet at 10,000 g centrifugation followed by 600 g centrifugation). Association constant (Ka) and maximal binding capacity (MBC) showed the lowest level at 15 days gestation in rat uterus. These seemed to effectively maintain pregnancy by inhibiting uterine contraction. Both Ka and MBC were increased in the uterus of intrapartum rat compared with that of prepartum, but the former was about 45%, and the latter was almost the same as, that of non pregnant rat. PMID- 2874182 TI - [A case of multiple endocrine neoplasia type 1 with growth hormone and prolactin secreting pituitary adenoma, functioning large parathyroid cyst, and Zollinger Ellison syndrome]. PMID- 2874183 TI - Seminiferous tubule androgen receptors in experimental cryptorchidism. AB - As an initial approach to the study of seminiferous tubule androgen receptors in disordered spermatogenesis, cytosol androgen receptors were studied in rats with experimental cryptorchidism. Two weeks after the testis had been repositioned in the abdomen of 6-week-old rats, the animals were hypophysectomized to deplete the testis of androgen, and 1 week later they were killed. Androgen receptor binding was studied in seminiferous tubule cytosol using [3H]methyltrienolone as the radiolabelled probe. The androgen-binding capacity of cryptorchid testis, when expressed as fmol bound/testis, was reduced to 50% of control, in parallel with the decline in testis weight. No change in binding affinity was found. Sucrose density gradient centrifugation using a vertical tube rotor revealed a 9S molybdate-stabilized receptor under low-salt conditions in both cryptorchid and scrotal seminiferous tubule cytosol. Receptor-complex stability studies, analysis by gel filtration and DEAE-cellulose chromatography produced similar results in cryptorchid and scrotal tubules. The mechanism for the reduction in testicular receptor content of an abdominal testis remains to be clarified. The demonstration that testicular androgen receptors can be reduced by cryptorchidism suggests that further studies may indicate the role of receptor binding in testicular function. PMID- 2874184 TI - Somatostatin immunoneutralization stimulates thyroid function in fowl. AB - The influence of somatostatin on thyroid function has been examined in immature domestic fowl passively immunized with somatostatin antiserum. Plasma thyroxine (T4) and tri-iodothyronine (T3) concentrations were markedly increased within 10 min of antisomatostatin administration and remained raised for at least 5 h. The increases in the T3 and T4 concentrations following somatostatin immunoneutralization were directly related to the volume of antisera administered. The increase in the T3 concentration exceeded the increase in the T4 concentration, resulting in a T3 : T4 ratio greater than unity. While the raised T4 concentration began to decline 30 min after antisomatostatin administration, raised T3 concentrations were sustained for at least 2 h, and further increased the plasma T3 : T4 ratio. These results demonstrate that somatostatin immunoneutralization stimulates thyroid function in fowl. The magnitude and rapidity of the thyroidal responses to somatostatin immunoneutralization suggests that they occur independently of the hypothalamic pituitary-thyroid axis. Somatostatin appears to exert a tonic inhibitory control on avian thyroid function, possibly by effects mediated at the thyroid gland to inhibit T4 release and by peripheral effects to suppress the conversion of T4 and T3. PMID- 2874185 TI - Carboxyhemoglobin and serum hepatic enzymes in newborns with hyperbilirubinemia. PMID- 2874186 TI - Chance discovery of multiple personality disorder in a depressed patient by amobarbital interview. AB - Although the diagnosis of multiple personality disorder (MPD) has been receiving renewed interest in the literature, it presents a number of clinical problems and challenges. A case study is reported in which this diagnosis was uncovered by chance during an amobarbital interview on a psychotically depressed young male patient. The patient had previously been only minimally responsive to pharmacotherapy for a major depressive episode with mood-congruent psychotic features. When the multiple personality disorder was diagnosed, treatment emphasis shifted toward psychotherapeutic modalities with marked clinical improvement. Several unique aspects of the case, including diagnostic methodology, results of serial dexamethasone suppression tests, and psychosomatic symptomatology, are discussed as well as the implications of this case within a larger clinical context. PMID- 2874187 TI - A bioluminescence method for the measurement of L-glutamate: applications to the study of changes in the release of L-glutamate from lateral geniculate nucleus and superior colliculus after visual cortex ablation in rats. AB - We have developed a rapid, simple, specific, and very sensitive bioluminescence method for the measurement of L-glutamate (L-Glu). Oxidation of L-Glu by glutamate dehydrogenase has been coupled with bacterial FMN reductase and luciferase. Light production (i.e., peak height or integral) was linear from less than 0.5 to 500 pmol of L-Glu. Potential interfering substances that may be encountered in brain tissue have been identified. The most potent inhibitors were ascorbate and the biogenic amines. Procedures that conferred long-term stability of the reagent mixture (greater than 8 h) were established. Bioluminescence analysis of L-Glu content in brain tissue extracts, fractions from release experiments, and human CSF corroborated respective results obtained by HPLC analysis. In this study, we have applied the method to monitor changes in the KCl evoked release of endogenous L-Glu from milligram amounts of brain tissue, i.e., from lateral geniculate nucleus and superior colliculus after visual cortex ablation. PMID- 2874188 TI - Amino acid levels in the guinea pig spinal gray matter after axotomy of primary sensory and descending tracts. AB - This study attempts to determine if the axonal endings of dorsal root sensory fibers and of descending axons to the spinal gray matter in the guinea pig store glutamate and/or aspartate. Bilateral dorsal rhizotomy (spinal segments C5-T1) and partial cordotomy (segment C5, right side) were used to interrupt primary sensory and descending tracts, respectively. At 1 and 2 days after surgery, amino acid levels were determined in regions microdissected from areas of the gray matter of spinal segment C7 that receive heavy projections from the primary sensory and the descending tracts. These regions were identified by visualizing the degeneration of axons and their terminal fields in silver-impregnated light microscopic preparations of the spinal cord. After dorsal rhizotomy, the heaviest degeneration in the spinal gray appeared centrally in laminae II-IV and medially in laminae IV-VI. The levels of aspartate, glutamate, and gamma-aminobutyrate were reduced by 34, 21, and 26% in laminae II-IV and 28, 33, and 23% in medial laminae IV-VI. The levels of glycine, alanine, and threonine-serine-glutamine (unseparated) were increased. After partial cordotomy, the heaviest degeneration in the spinal gray appeared laterally in laminae IV-VI, dorsolaterally in lamina VII, and in lamina IX. The levels of aspartate and glutamate were reduced by 22 and 28% in lateral laminae IV-VI and by 26 and 28% in dorsolateral laminae VII and IX. Glycine levels were reduced by 9% in dorsolateral laminae VII and IX. The levels of gamma-aminobutyrate, alanine, and threonine-serine-glutamine were either unchanged or raised. These findings suggest that the axonal endings of the primary sensory and of one or more of the descending tracts probably contain relatively high levels of glutamate and aspartate, and that they may use these amino acids as transmitters. The partial deafferentation of spinal interneurons and the destruction of some propriospinal fibers probably caused the losses of gamma-aminobutyrate and glycine, and contributed modestly to those of aspartate. PMID- 2874190 TI - Changes in nine enzyme markers for neurons, glia, and endothelial cells in agonal state and Huntington's disease caudate nucleus. AB - Enzymes considered to be markers for neurons (angiotensin converting enzyme, thermolysin-like metalloendopeptidase, alanine aminopeptidase, and glutamate oxaloacetate transaminase), glia (glutamine synthetase, pyruvate carboxylase, and beta-glucuronidase), and endothelial cells (alkaline phosphatase and plasminogen activator) were measured in caudate nucleus from 10 sudden death controls, eight agonal state controls, and 16 Huntington's disease patients. Glutamate oxaloacetate transaminase was slightly reduced by agonal state. The four enzymes with a neuronal distribution were all correlatively reduced in Huntington's disease caudate nucleus. Glutamine synthetase activity was reduced and beta glucuronidase mean activity increased over twofold in Huntington's disease caudate nucleus, with the two enzyme activities being inversely related. Pyruvate carboxylase was markedly affected by agonal state and was very variable in Huntington's disease caudate nucleus. The two endothelial enzymes were unaltered in Huntington's disease caudate nucleus. The findings are indicative of neuronal loss, an increased proportion of altered glia, and also of maintained vasculature in Huntington's disease caudate nucleus. Measurement of enzyme activities can help to delineate the types of cell altered in Huntington's disease. PMID- 2874189 TI - Activation of glutamate apodecarboxylase by succinic semialdehyde and pyridoxamine 5'-phosphate. AB - Glutamate apodecarboxylase was activated by incubation with succinic semialdehyde and pyridoxamine 5'-phosphate. Activation required both compounds and was highly selective for succinic semialdehyde. Of 18 analogs tested, only glyoxylate, pyruvate, oxaloacetate, and 2-oxoglutarate activated the apoenzyme significantly, but much higher concentrations of these compounds than of succinic semialdehyde were required. In the presence of pyridoxamine 5'-phosphate, the concentration of succinic semialdehyde giving half-maximal activation of apoenzyme was 7 microM. In contrast, the Ki for succinic semialdehyde as a competitive inhibitor of glutamate decarboxylation was 1.2 mM, indicating that apoenzyme with bound pyridoxamine 5'-phosphate has a much higher affinity for succinic semialdehyde than does holoenzyme. The concentration of pyridoxamine 5'-phosphate giving half maximal activation was 17 microM, which is more than an order of magnitude greater than the corresponding value for pyridoxal 5'-phosphate. PMID- 2874191 TI - Caffeine ingestion by rats increases noradrenaline turnover and results in self biting. AB - The effects of caffeine on the activity of central and peripheral catecholaminergic structures have been studied in rats ingesting high doses of caffeine. The activities of the enzymes tyrosine hydroxylase and dopamine-beta hydroxylase were measured as well as 3,4-dihydroxyphenylethylamine (dopamine), adrenaline, and noradrenaline concentrations, in brain (striatum and hypothalamus), heart, and adrenal gland. At the peripheral level, we observed a significant increase in the dopamine and adrenaline plus noradrenaline content in the heart, but an increase in dopamine content only was found in the adrenal gland. Dopamine-beta-hydroxylase activity in serum was increased, but the only significant enzymic change in brain was an increase in the dopamine-beta hydroxylase activity of the hypothalamus. However, an increase in catecholamine content was observed in both structures of the brain. These data suggest that the mechanisms involved in caffeine-induced self-biting in rats are not limited to the dopaminergic system, because we have also observed an increase in noradrenaline turnover. PMID- 2874192 TI - An examination of the involvement of phospholipases A2 and C in the alpha adrenergic and gamma-aminobutyric acid receptor modulation of cyclic AMP accumulation in rat brain slices. AB - Experiments were undertaken to define the role of two calcium-associated enzyme systems in modulating transmitter-stimulated production of cyclic nucleotides in rat brain. Cyclic AMP (cAMP) accumulation was examined in cerebral cortical slices using a prelabeling technique. The enhancement of isoproterenol-stimulated cAMP production by alpha-adrenergic and gamma-aminobutyric acid-B (GABAB) agonists was reduced by exposing the tissue to EGTA, a chelator of divalent cations, or quinacrine, a nonselective inhibitor of phospholipase A2. Likewise, chronic (2 weeks) administration of corticosterone decreased the alpha-adrenergic and GABAB receptor modulation of second messenger production. Neither cyclooxygenase nor lipoxygenase inhibitors selectively influenced the facilitating response of alpha-adrenergic and GABAB agonists. Other experiments revealed that although norepinephrine and 6-fluoronorepinephrine stimulated inositol phosphate (IP) production in cerebral cortical slices with potencies equal to those displayed in the cyclic nucleotide assay, selective alpha 1 adrenergic agonists were less efficacious on IP formation and were without effect in the cAMP assay. Conversely, a selective alpha 2-adrenergic receptor agonist facilitated the cAMP response to a beta-adrenergic agonist without affecting IP formation. The rank orders of potency of a series of alpha-adrenergic antagonists suggest that IP accumulation is mediated solely by alpha 1-adrenergic receptors, whereas the augmentation of cAMP accumulation is regulated by a mixed population of alpha-adrenergic sites. The results suggest that the alpha-adrenergic and GABAB receptor-mediated enhancement of isoproterenol-stimulated cAMP formation appears to be more closely associated with phospholipase A2 than phospholipase C and may be mediated by arachidonate or some other fatty acid. PMID- 2874193 TI - Na+-dependent "binding" of D-aspartate in brain membranes is largely due to uptake into membrane-bounded saccules. AB - Na+-dependent "binding" of acidic amino acids in brain plasma membranes was examined by procedures similar to those employed in earlier studies, using the metabolically inert D-[3H]aspartate as a probe. The "binding" showed characteristics similar to those described before in terms of affinity (KD, 400 nM), density of sites (Bmax, 300 pmol/mg protein), sensitivity to D,L-threo-3 hydroxyaspartate, and requirement for Na+. It turned out that the "binding" represents uptake into membrane-bounded saccules (which according to the inulin and H2O spaces constituted 3.4 microliters/mg protein and comprised about 50% of the volume of the sedimented membranes), rather than binding to the transport carrier. This conclusion is based on the observations that the "binding" of D aspartate was released by osmotic shock; was abolished by thorough washing of membranes in H2O prior to assay, which removed endogenous contents of amino acids, and could be recovered by loading the washed membranes with glutamate; was reduced by prior freezing and thawing; was low on incubation at 0 degree C; had a bell-shaped time course similar to that reported for uptake; and had a slow rate of reversal compared to the apparent KD. True binding would have considerably lower apparent Bmax than the carrier-mediated uptake. This and its likely rapid rate of dissociation would make binding to the carrier difficult to detect by the methods used up to now. PMID- 2874194 TI - Tyrosine hydroxylase activation in mesocortical 3,4-dihydroxyphenylethylamine neurons following footshock. AB - Mild electric footshock resulted in activation of tyrosine hydroxylase (TH) in prefrontal cortex of mice and rats. In mice, the activation was also observed following restraint. Shock-evoked activation of prefrontal cortex TH was characterized by a decrease of apparent Km for the pterin cofactor 6-methyl 5,6,7,8-tetrahydropterin and an increase of Vmax. Activation of prefrontal cortical TH was also demonstrated in vitro following preincubation under conditions that activate cyclic AMP-dependent protein kinase. Treatment of mice with the noradrenergic neurotoxin N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP 4) caused a 70% decrease in prefrontal cortex norepinephrine levels but had no significant effect on the activity of TH in that brain region. Footshock resulted in the activation of prefrontal cortex TH of DSP-4-treated mice, suggesting that shock-evoked activation of the enzyme occurs in terminals of mesocortical 3,4 dihydroxyphenylethylamine neurons. PMID- 2874195 TI - Management of subdural intracranial empyemas should not always require surgery. AB - Seven patients with subdural empyema were initially treated by antibiotics without surgery. Six have recovered without sequelae. One required delayed surgery and has recovered with epilepsy. The authors emphasise the use of CT for the diagnosis and follow-up of subdural empyema, the principles and modalities of non-surgical treatment, and the good results, especially for late morbidity. PMID- 2874196 TI - A phase I study of intravenous azimexon therapy in human cancer. AB - Azimexon, a synthetic derivative of the 2-cyanaziridines, was given intravenously daily for 5 days to 19 cancer patients in a Phase I trial designed to determine the drug's tolerable dose, toxicity, and effects on immune and nonimmune host defense parameters. No myelosuppression, neurologic, renal, hepatic, or gastrointestinal toxicities could be detected. The only toxic side effect observed after 5 days of intravenous azimexon was a self-limiting dose-dependent hemolysis. Absolute lymphocyte count (ALC) increased from a pretreatment value of 0.96 X 10(3)/microliter to 1.56 X 10(3)/microliter on day 21 (p less than 0.05). This increase was induced primarily by the less hemolytic 200-250 mg/m2 doses of azimexon. Among 12 patients given this lower dosage. ALC increased from an average initial value of 0.90 X 10(3)/microliter to 1.86 X 10(3)/microliter on day 21 (p less than 0.01). Absolute number of OKT3+ cells increased from 0.524 to 0.914 X 10(3)/microliter (p less than 0.05) with lower drug doses. The mean absolute number of OKT4+ cells increased from 0.294 on day 0 to 0.574 X 10(3)/microliter on day 21 (p less than 0.05), and the number of OKT8+ cells increased from 0.202 to 0.388 X 10(3)/microliter, with no significant changes in helper/suppressor ratio. Significant increases in mitogenic responses to phytohemagglutinin (PHA) [from 13.4 to 35.7 X 10(3) net cpm (p less than 0.05)] and to concanavalin A (con A) [from 6.4 to 25.6 X 10(3) net cpm (p less than 0.05)] were also observed with higher drug doses. Azimexon may have a role in managing cancer-associated dysregulation of the immune response. PMID- 2874197 TI - Receptors for excitatory amino acids on neurons in rat pyriform cortex. AB - The actions of a variety of agonists and antagonists of the excitatory amino acids on rat pyriform cortex pyramidal neurons were studied in a submerged, perfused brain slice. The order of potency for the agonists, applied by ionophoresis, was kainate greater than quisqualate greater than N-methyl-D aspartate greater than aspartate = glutamate. The endogenous monosynaptic excitation of pyramidal neurons upon stimulation of the lateral olfactory tract was blocked post-synaptically by DL-2-amino-4-phosphonobutyric acid, although this drug did not consistently block any of the exogenous responses. The synaptic excitation was not blocked, however, by antagonists presumed specific for the quisqualate (glutamate diethyl ester), kainate, (gamma-D-glutamylglycine), or N methyl-D-aspartate (DL-2-amino-5-phosphonovaleric acid, DL-2-amino-7 phosphonohetaonic acid) receptors. Several antagonists blocked N-methyl-D aspartate responses at lower concentrations than those to aspartate, and other antagonists distinguished between kainate and quisqualate responses. These results suggest that 1) pyriform neurons have a variety of receptors that have properties somewhat different from those found in other preparations and 2) the endogenous transmitter activates a receptor distinct from those activated by kainate, quisqualate, and N-methyl-D-aspartate. PMID- 2874198 TI - Factors affecting release of 3H-dopamine from perfused carp retina. AB - The effects of putative retinal neurotransmitters and several neuropeptides on 3H dopamine release from isolated perfused carp (Cyprinus carpio) retinas were studied. Of the transmitter candidates tested, only serotonin (5-HT) and the 5-HT agonist tryptamine released 3H-dopamine. However, the release evoked by these agents was calcium (Ca2+) independent and not blockable by the 5-HT antagonist methysergide. We also investigated the antagonism of inhibitory inputs as a potential regulatory mechanism for dopamine release and found that the GABA antagonists, bicuculline and picrotoxin, stimulated a dose-dependent release of 3H-dopamine. The effects of the GABA antagonists were dependent on extracellular Ca2+ and could be inhibited by perfusion of the retina with GABA. Bicuculline and picrotoxin also stimulated an increase in cAMP accumulation, which was inhibited by the dopamine antagonist haloperidol. Our results support the hypothesis that the dopaminergic interplexiform cells of the teleost retina are under GABAergic inhibitory control. PMID- 2874199 TI - Branching of sensory and sympathetic neurites in vitro is inhibited by treatment with taxol. AB - Branching of elongating neurites in vitro occurs by the division of a growth cone into 2 or more daughter neurites. An important initial step is a broadening of the growth cone with establishment of a quiescent central growth cone margin. Within the spreading growth cone, microtubules and associated neuritic components diverge and become oriented toward the lateral protrusive margins of the leading edge (Letourneau, 1983). We have found that a low concentration of the microtubule-stabilizing agent taxol severely reduces the incidence of growth cone branching by cultured sensory and sympathetic neurons from chick embryos. In the presence of taxol, neurites are broader and have more microtubules than normally. Divergence of microtubules entering the growth cone from the proximal neurite is reduced in the presence of taxol, and quiescence of the central growth cone margin is less frequent. We propose that a critical step in branching is the separation and spreading of the neurite cytoskeleton by tensions generated at the lateral margins of the edge of the growth cone. Because taxol increases neurite size and microtubule content without increasing protrusive activity to the same extent, tensions produced in the motile leading edge are insufficient to spread the microtubules and associated neuritic materials into separate arrays for nascent branches. PMID- 2874200 TI - Neurotransmitter delivery. PMID- 2874201 TI - Identification of histiocytic reticulum cells by the immunohistochemical demonstration of factor XIII (F-XIIIa) in human lymph nodes. AB - Morphologically and enzyme histochemically distinguishable tissue macrophages and stromal cells of human reactive lymph nodes were characterized by the cytoplasmic presence of the subunit A of factor XIII and by the expression of surface antigenic determinants reacting with monoclonal antibodies directed against monocyte/macrophage populations (Mo 1, Leu M3) and HLA-DR antigens. The distribution of F-XIIIa positive cells was studied on formaldehyde-fixed paraffin embedded sections with immunoperoxidase techniques. established on cryostat section with double immunofluorescence. Alpha-Naphthyl acetate esterase (ANAE) reaction was The immunophenotype was established on cryostat sections with double immunofluorescence. Alpha-Naphthyl acetate esterase (ANAE) reaction was carried out on these cryostat sections to identify tissue macrophages. The antibody against F-XIIIa detected histiocytes in both intra- and extra-sinusoidal locations which were ANAE+, Mo 1+, Leu M3+ and HLA-DR-. F-XIIIa was also present in fibroblast-like mesenchymal cells with the following phenotypic characteristics: ANAE-, Mo 1+, Leu M3+ and HLA-DR+. The anti F-XIIIa antibody did not stain lymphoid cells, granulocytes, epithelial cells, endothelial cells and mast cells. The immunohistochemical detection of F-XIIIa works on formaldehyde fixed paraffin-embedded sections. The most promising application seems to be the identification of histiocytes in lymphoid and histiocytic proliferations. PMID- 2874202 TI - The international scheduling of OTC inhaler ingredients: an abuse perspective. PMID- 2874203 TI - Effects of anticonvulsive drugs on the activity of gammaglutamyltransferase and aminotransferases in serum. AB - A cross-sectional study was performed to define patients at risk of developing liver disease due to long-term treatment with anticonvulsive drugs. The activities of gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase and the concentrations of primidone, phenobarbital, phenytoin, and valproic acid in serum were estimated. Epileptic children before therapy were used as controls. The results indicated enzyme induction due to phenobarbital and both enzyme induction and liver cell damage or plasma membrane leakage due to phenytoin. Gamma-glutamyltransferase may be an early indicator of liver disease due to valproic acid. PMID- 2874204 TI - Course and prognosis of idiopathic ulcerative proctosigmoiditis in young patients. AB - The course and prognosis of idiopathic ulcerative proctosigmoiditis were studied in 85 young patients whose symptoms had begun before the age of 21 (mean age at onset, 16 years), and the results were compared with those in adults with proctosigmoiditis. Data regarding extension of disease, available in 66 patients, allowed us to identify two groups of patients. Presenting symptoms were the same in both groups. In Group I (41 patients, 62%), the disease remained stable or did not extend beyond the descending colon. In Group II (25 patients, 38%), there was evidence of extension to the hepatic flexure or beyond. Extension was unpredictable in individual patients, but generally occurred within 5 years from the onset of symptoms (73%). The clinical course and prognosis were different in each group. In Group I, there were more females, the disease ran a milder course, and there were few complications. In Group II, there were relatively more males, the disease was more active and severe, and a high incidence of intestinal and extraintestinal complications was observed. Fifteen patients, all from Group II, required colectomy. The natural history of proctosigmoiditis in young patients is somewhat different from that in adults, being characterized by a greater tendency to proximal extension (38% vs. 10%). However, when the disease remains confined to the rectosigmoid region (or does not spread beyond the splenic flexure), the course and prognosis are no different than in adults. PMID- 2874205 TI - Affinity of tocolytic agents on human placental and myometrial beta-adrenergic receptors. AB - The beta-adrenoreceptor antagonist [3H]-dihydroalprenolol (DHA) has been used to label adrenoreceptors in membranes from human pregnant myometrium and placenta. Six tocolytic drugs were tested for their ability to bind to the beta-adrenergic receptor of placental and myometrial membranes. Tocolytic agents competed with [3H]-DHA binding in the following order of potency: clenbuterol greater than fenoterol greater than ritodrine greater than isoxsuprine greater than orciprenaline greater than terbutaline. All drugs competed for [3H]-DHA binding sites with HILL coefficients greater than unity indicating heterogeneity of binding. In general, binding of beta-adrenoreceptor agonists was weaker in myometrium than in placenta homogenates. According to our results it is very likely that the placenta may play an important role in the pharmacological mechanism of tocolytic agents in inhibitory of premature labor. PMID- 2874206 TI - Pharmacological studies of imidazoline derivatives. II. Agonistic and antagonistic actions on alpha-adrenoceptors in various smooth muscle preparations. AB - The effects of 8 imidazoline derivatives on alpha-adrenoceptor-mediated contraction or relaxation of various kinds of smooth muscle preparations were investigated. In rabbit aortic strips, K-6341, K-6343 and K-4011 produced alpha agonistic action which was antagonized by prazosin. In the study of alpha antagonistic action of imidazoline derivatives, i.e. antagonism against norepinephrine- or phenylephyrine-induced contraction of the rabbit aortic strip, the order of potency series, prazosin greater than phentolamine greater than yohimbine greater than K-4011, K-3827, K-4300 greater than tolazoline was found. Reserpine pretreatment did not affect the results. In the study of alpha antagonistic effect on the relaxing response to norepinephrine of methacholine contracted rat ileum, the potency series was revealed as follows: prazosin greater than phentolamine greater than yohimbine greater than K-4011, K-3827, K 4300, tolazoline. A similar experiment was performed on histamine-contracted guinea-pig taenia coli, and the results were nearly identical to the case of the rat ileum, except that K-6341 and K-6343 also exhibited alpha-antagonistic action which was not detected in the rat ileum. This suggests that alpha 2-receptor may exist in the postsynaptic alpha-adrenoceptor in the guinea-pig taenia coli. The results of the present study indicate that the potency of imidazoline derivatives to inhibit norepinephrine-induced contraction of some smooth muscle is almost identical to that which inhibited norepinephrine-induced relaxation of other smooth muscles. Furthermore, K-4300 was found to possess anti-acetylcholine and anti-histamine actions in the guinea-pig taenia coli and anti-serotonin action in the rat fundus strips. PMID- 2874207 TI - Reversal of antinociceptive effect of caerulein by benzodiazepine. AB - Benzodiazepines, chlordiazepoxide and diazepam reversed the antinociceptive action of caerulein in mice. Benzodiazepines (1-5 mg/kg) were administered intraperitoneally and 100 ng of caerulein was injected intracisternally to mice. Benzodiazepines did not change the basal pain threshold of mice but significantly antagonized the antinociceptive effect of caerulein. Proglumide (200 mg/kg, i.p.), which has been claimed to be a specific cholecystokinin receptor antagonist, could also antagonize the antinociceptive effects of caerulein. Naloxone (5 mg/kg) partially but significantly antagonized the antinociceptive effect of caerulein, suggesting that one of the mechanisms of antinociceptive action of caerulein is related to endogenous opioid peptides since benzodiazepines do not act on opioid receptors. Benzodiazepines may decrease the antinociceptive effect of caerulein through acting on cholecystokinin receptors in the central nervous system. PMID- 2874208 TI - Biochemical studies on Mycobacterium leprae. AB - Very little information is available on the basic biology of Mycobacterium leprae. It is not known why the organism fails to grow in bacteriological media or in cell cultures and why it has an unusual predilection for certain tissues in the human host where cells derived from the neural crest occur (e.g. skin, peripheral nerves, adrenal medulla). Biochemical studies have revealed that M. leprae contains an unusual form of the enzyme diphenoloxidase which has not been detected in other mycobacteria. The presence of a specific glutamic acid decarboxylase in the organism has been demonstrated. Although a few enzymes of glycolysis and tricarboxylic acid cycle have been investigated, nothing characteristic of the bacterium has been discovered, and how M. leprae derives energy for its survival and proliferation still remains obscure. PMID- 2874209 TI - High performance liquid chromatographic determination of the enantiomers of beta adrenoceptor blocking agents in biological fluids. I: Studies with pindolol. AB - This paper describes a high-performance liquid chromatographic procedure for the analysis of (+)- and (-)-pindolol in biological fluids. Racemic pindolol is extracted from alkalinized plasma or urine into ether, then purified by two steps of back extraction. The final extract is reacted with (S)-(-)-alpha-methylbenzyl isocyanate at room temperature, forming urea diastereoisomers as suggested by mass spectral analysis. Separation of the two diastereoisomers is accomplished by high-performance liquid chromatography with fluorescence detection. The assay is reproducible and precise for both (+)- and (-)-pindolol in human plasma and urine, as judged by a coefficient of variation of less than 10% at most concentrations. The standard curves for (+)- and (-)-pindolol in plasma are linear between 10-100 ng/mL, and between 100-2500 ng/mL in urine. The lower limit of detection is approximately 2 ng/mL for each enantiomer in plasma. This procedure can be readily adapted for the stereospecific assay of other beta adrenoceptor blocking agents as demonstrated by the base-line separation of atenolol and acebutolol. PMID- 2874210 TI - CI-926 (3-[4-[4-(3-methylphenyl)-1-piperazinyl]butyl]-2,4-imidazolinedione): antihypertensive profile and pharmacology. AB - CI-926 (10(-7)-10(-6) M) selectively antagonized the contraction of isolated rabbit aortae to phenylephrine and displaced the alpha-1 adrenoceptor ligand WB4101 (IC50: 82 nM) in rat brain. In the spontaneously hypertensive rat, single oral doses of either CI-926 (0.3-10 mg/kg) or prazosin (0.3-100 mg/kg) caused dose-related reductions in blood pressure; however, CI-926 was more efficacious. The maximal antihypertensive response to CI-926 was unchanged with three consecutive days of oral dosing in the spontaneously hypertensive rat, whereas a first dose effect was noted with prazosin. In two-kidney, one-clip, renal hypertensive rats, CI-926 and prazosin (1-10 mg/kg) lowered blood pressure; however, prazosin was more efficacious. In perinephritic hypertensive dogs, CI 926 (10 mg/kg) lowered blood pressure 20%. In anesthetized dogs, CI-926 in the presence of supermaximal blood pressure-lowering doses of prazosin caused an additional reduction in pressure. With equivalent alpha-1 blockade in anesthetized rats, CI-926 tended to have greater hypotensive activity than prazosin. These results demonstrate that CI-926 is a potent, orally active antihypertensive agent in renin-dependent and -independent hypertension. The profile of CI-926 suggests that it lowers blood pressure in part by interacting with peripheral alpha-1 adrenoceptors and in part via an additional mechanism(s). Although weak relative to its affinity for alpha-1 adrenoceptors, CI-926 was found in preliminary experiments to interact with alpha-2 adrenoceptors, serotonergic receptors and dopaminergic receptors. The importance of these interactions to the blood pressure response of CI-926 remains to be elucidated. PMID- 2874211 TI - Development of high sodium renal hypertension during chronic blockade of the vascular effects of vasopressin. AB - Studies in sodium-dependent models of hypertension have shown that arginine vasopressin (AVP) plays an important role in the maintenance of blood pressure, predominantly through its vasoconstrictor action. In addition to AVP, the sympathetic nervous system (SNS) also acts to maintain blood pressure in high sodium one-kidney, figure-8 renal wrap hypertension. The purpose of this study was to determine if chronic blockade of vascular AVP (V1) receptors affected the induction of high sodium renal hypertension and the contribution of the SNS to the maintenance of blood pressure. Rats receiving chronic s.c. administration of a V1 antagonist, d(CH2)5Tyr(Me)AVP, or vehicle were subjected to renal wrapping or sham surgery, V1 receptor blockade was confirmed periodically by an 80 +/- 3% reduction of the pressor response to a bolus injection of 10 mU/kg of AVP. d(CH2)5Tyr(Me)AVP did not affect the development of hypertension or the associated changes in plasma sodium, potassium, osmolality and hematocrit. In renal-wrapped rats, ganglionic blockade caused a greater fall in blood pressure in animals treated with d(CH2)5Tyr(Me)AVP than in vehicle-treated animals. However, this apparent increase in SNS function was not responsible for the hypertension in d(CH2)5Tyr(Me)AVP-treated, renal-wrapped rats, inasmuch as ganglionic blockade lowered blood pressure a similar amount in normotensive d(CH2)5Tyr(Me)AVP-treated, sham-operated rats and blood pressure remained elevated after combined blockade of the SNS, AVP and the renin-angiotensin systems. These results indicated that chronic blockade of V1 receptors did not alter the induction of high sodium renal hypertension and the mechanism of the elevated blood pressure was not through an activation of the SNS or other neurohumoral mechanisms. PMID- 2874212 TI - Behavioral effects of zopiclone, CL 218,872 and diazepam in squirrel monkeys: antagonism by Ro 15-1788 and CGS 8216. AB - The effects of zopiclone, CL 218,872 and diazepam were compared in squirrel monkeys trained to respond under a fixed-interval (FI) schedule of food presentation. Dose-response curves were determined for each drug by administering cumulative doses i.v. during timeout periods that preceded sequential components of the FI schedule. Low and intermediate doses of zopiclone (0.03-1.0 mg/kg), CL 218,872 (0.3-3.0 mg/kg) or diazepam (0.1-1.0 mg/kg) produced dose-related increases in the rate of FI responding. The highest doses of diazepam (10.0 mg/kg) and CL 218,872 (30.0 mg/kg), but not of zopiclone (30.0 mg/kg), decreased FI responding markedly. Doses of zopiclone, CL 218,872 and diazepam that were effective in increasing FI responding were similar to the doses reported previously to increase suppressed (punished) responding in squirrel monkeys. Pretreatment with the benzodiazepine antagonists Ro 15-1788 or CGS 8216 (1.0 or 3.0 mg/kg) reduced or eliminated the increases in FI responding produced normally by intermediate doses of zopiclone, CL 218,872 or diazepam, suggesting that the rate-increasing effects of the three agonists reflect similar actions at benzodiazepine recognition sites. In contrast, Ro 15-1788 and CGS 8216 were less effective or ineffective in attenuating the marked decreases in FI responding produced by the highest doses of CL 218,872 or diazepam, suggesting that the rate decreasing effects of these agonists are mediated differently from their rate increasing effects. PMID- 2874213 TI - Activation of DA1 receptors by dopamine or fenoldopam increases cyclic AMP levels in the renal artery but not in the superior cervical ganglion of the rat. AB - In the isolated superior cervical ganglion of the rat, activation of either DA1 or DA2 receptors leads to inhibition of ganglionic transmission. Using dopamine as well as relatively selective dopamine receptor agonists and antagonists we have performed electrophysiological as well as biochemical experiments to study the nature of dopamine receptors in this sympathetic ganglion. Fenoldopam, a selective DA1 receptor agonist caused marked inhibition of the compound postganglionic action potential evoked by stimulation of preganglionic nerve. The inhibitory effect of fenoldopam was antagonized by the DA1 receptor antagonist R sulpiride but not by the DA2 receptor antagonist S-sulpiride. However, the more potent and selective DA1 receptor antagonist SCH-23390 failed to antagonize ganglion blocking effect of fenoldopam indicating that DA1 receptor in sympathetic ganglia is different from that in blood vessels. The superior cervical ganglion also contains DA2 receptors inasmuch as quinpirole, a DA2 receptor agonist, caused inhibition of ganglionic transmission which was antagonized by S-sulpiride but not by R-sulpiride. The existence of both subtypes of dopamine receptor in the superior cervical ganglion was ascertained further as dopamine itself caused inhibition of ganglionic transmission which was antagonized by either S- or R-sulpiride. Again, however, the DA1 receptor antagonist SCH-23390 failed to antagonize the ganglion blocking effect of dopamine. To characterize further the ganglionic DA1 receptor we sought to demonstrate whether or not ganglionic DA1 receptor is linked to the enzyme adenylate cyclase as is known to be the case for peripheral DA1 or central D1 dopamine receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2874214 TI - Pharmacological comparison of ORF 17910, a potent, long-acting histamine H2 receptor antagonist, to cimetidine and ranitidine. AB - This paper describes the pharmacology of ORF 17910, a specific, long-acting histamine H2-receptor antagonist. ORF 17910 (ED50 = 0.26 mg/kg) is 26 and 2.7 times more potent p.o. than cimetidine and ranitidine, respectively, at inhibiting acid output in betazole-stimulated total gastric fistula dogs. When given i.v., ORF 17910 (ED50 = 0.06 mg/kg) is 3.6 times more potent than ranitidine. Qualitatively similar antisecretory potency differences are seen in rats (ED50 = 3.7 mg/kg intraduodenal). ORF 17910 retains 43 and 37% of its antisecretory potency 16 hr after dosing in dogs and rats, respectively, suggesting a long duration of action, whereas ranitidine is either inactive (rats) or loses 97% of its potency (dogs) at this time. When the parenteral and enteral (p.o. or intraduodenal) potencies of ORF 17910 and ranitidine are compared, ORF 17910 appears less bioavailable than ranitidine, although this difference is greater in the rat than in the dog and diminishes with time. In rabbit isolated parietal cell (pA2 = 7.96) and guinea pig isolated atria preparations (pA2 = 7.51), ORF 17910 is more potent than both cimetidine and ranitidine at inhibiting the effects of histamine. At high concentrations, the inhibitory effect of ORF 17910 in atria can not be overcome completely, a property which may contribute to its long duration of action in vivo. In several additional test systems, ORF 17910 does not exhibit any biologically significant pharmacology and appears to be specific for the histamine H2-receptor. PMID- 2874215 TI - Further characterization of the presynaptic alpha-1 receptor modulating [3H]ACh release from rat atria. AB - We have reported previously that norepinephrine (NE) and epinephrine reduce acetylcholine (ACh) overflow from superfused rat atria apparently through interaction with a presynaptic alpha-1 receptor. To characterize further this novel alpha-1-mediated effect, we tested the ability of a series of alpha antagonists and agonists to modulate ACh release in this preparation. The alpha-1 selective antagonists YM 12617 and WB 4101 blocked the inhibitory action of NE with IC50 values of about 0.1 and 1 nM, respectively, whereas the alpha-2 selective antagonists Wy 26703 and rauwolscine were much less potent. These data are consistent with the involvement of an alpha-1 receptor in the response to NE. ACh release was diminished by (-)-alpha-methyl-NE but similar concentrations of the alpha-2 selective agonists B-HT 920 and UK 14304 had no effect on ACh release. A number of alpha-1 selective agonists including amidephrine, cirazoline, St 587 and SK&F 89748 failed to inhibit [3H]ACh release or had only a small effect (phenylephrine). When tested as antagonists, however, phenylephrine, cirazoline and SK&F 89748 could block the inhibitory effect of NE at concentrations consistent with their affinities at alpha-1 receptors in other systems. These compounds thus bind to but do not activate the alpha receptor regulating ACh release, apparently due to their low efficacies compared to NE. Experiments carried out after alpha receptor inactivation with phenoxybenzamine demonstrate that there is little receptor reserve for the inhibition of ACh release by NE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2874216 TI - Pharmacological studies on stress-induced increase in frontal cortical dopamine metabolism in the rat. AB - The effects of a variety of minor tranquilizers and of benzodiazepine inverse agonists on the stress-induced increase in frontal cortical dopamine metabolism have been studied in the rat. Electric footshock stress increased 3,4 dihydroxyphenylacetic acid (DOPAC) levels in the frontal (but not parietal) cortex and in the nucleus accumbens but not in the striatum or ventral tegmental area. Similar stress-induced alterations of frontal cortical DOPAC levels were observed after DSP4-induced noradrenergic denervation or after adrenalectomy. Other types of stress, e.g. conditioned fear (exposure to an environment paired previously with footshock) or swim stress also provoked an elevation of DOPAC levels in the prefrontal cortex. When administered systemically, the anxiolytic agents meprobamate, CL 218,872, CGS 9896, suriclone and the hypnotic/anxiolytic drugs zolpidem and zopiclone all prevented the electric footshock stress-induced augmentation of cortical DOPAC levels whereas the gamma-aminobutyric acid receptor agonists progabide, muscimol and depamide or the sedative alpha-1 adrenoceptor antagonist prazosin were ineffective. The preventive effect of diazepam and zolpidem on the stress-induced biochemical response was antagonized by the benzodiazepine antagonist CGS 8216 but not by the gamma-aminobutyric acid receptor antagonist bicuculline. In nonstressed rats, systemic administration of the anxiogenic benzodiazepine inverse agonists beta-CCM (methyl-beta-carboline-3 carboxylate) and beta-CCE (ethyl-beta-carboline-3-carboxylate), but not of the benzodiazepine antagonists Ro 15-1788 or CGS 8216, caused an increase in frontal cortical DOPAC similar to that provoked by stress and which was antagonized by zolpidem.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2874217 TI - CH-38083, a selective, potent antagonist of alpha-2 adrenoceptors. AB - The selectivity and specificity of CH-38083 [7,8-(methylenedioxi)-14-alpha hydroxyalloberbane HCl], a berbane derivative for alpha adrenoceptors has been studied and compared with yohimbine and idazoxan in peripheral tissues and in the central nervous system. In isolated tissue experiments CH-38083 was a competitive antagonist at presynaptic alpha-2 adrenoceptors on the axon terminals of the rat vas deferens (pA2 against xylazine = 8.17 +/- 0.06) and of the longitudinal muscle strip of guinea pig ileum (pA2 against xylazine = 8.07 +/- 0.20). As far as its postsynaptic alpha-2 adrenoceptor antagonistic activity is concerned its affinity in rat vas deferens (pA2 = 4.95 +/- 0.11) against l-phenylephrine and in rabbit pulmonary artery (pA2 = 5.38 +/- 0.33 against l-norepinephrine) was markedly less than that displayed for presynaptic sites. From pA2 values obtained in rat vas deferens the calculated alpha-1/alpha-2 adrenoceptor selectivity ratios for yohimbine, idazoxan and CH-38083 were 4.7, 117.5 and 1659, respectively. CH-38083 failed to show any affinity for histamine and muscarinic receptors and it even potentiated the effect of serotonin on atropinized longitudinal muscle strip of guinea pig ileum. It enhanced the release of [3H]norepinephrine from electrically stimulated mouse vas deferens loaded previously with labeled [3H]norepinephrine. In binding studies carried out in rat brain membrane preparations using [3H]prazosin and [3H]idazoxan, the selectivity ratios (Ki alpha-1/Ki alpha-2) proved to be 32.5, 289.5 and 1368 for yohimbine, idazoxan and CH-38083, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2874218 TI - Carbamazepine and 10,11-epoxycarbamazepine produce use- and voltage-dependent limitation of rapidly firing action potentials of mouse central neurons in cell culture. AB - Effects of the anticonvulsant, carbamazepine (CBZ), on mouse central neurons in cell culture were examined using intracellular recording techniques. Spinal cord and cortical neurons demonstrated sustained repetitive firing (SRF) of action potentials (APs) at high frequency in response to depolarizing current pulses. Hippocampal neurons fired rapidly only in the pressure of the calcium channel blocker verapamil (1 microM). Concentrations of CBZ equivalent to therapeutic anticonvulsant levels in cerebrospinal fluid (greater than 4.2 microM) limited firing to a few action potentials in all three cell types in parallel with use dependent reduction of AP maximal rate of rise (Vmax). Resting membrane properties and postsynaptic responses to ionophoretically applied gamma aminobutyric acid and glutamate were unaffected. The CBZ metabolite, 10,11 epoxycarbamazepine, limited SRF at a concentration (4 microM) encountered at therapeutic CBZ levels. Another major CBZ metabolite, the 10,11-diol, limited SRF only at concentrations greater than those encountered with therapeutic serum CBZ levels. In control medium, APs could be evoked at a maximal rate of 450 Hz while in CBZ (10.6 microM) AP frequency was limited to 100 to 200 Hz. Limitation of SRF was voltage-dependent and could be partially reversed, or prevented, by membrane hyperpolarization. In addition, recovery of Vmax of sodium-dependent action potentials from inactivation was slowed, suggesting an effect on voltage dependent sodium channels. CBZ and phenytoin effects of SRF were similar. We suggest that limitation of sustained high frequency repetitive firing may be a significant anticonvulsant action of carbamazepine. The 10,11-epoxy derivative of CBZ, but not the 10,11-diol, may contribute to anticonvulsant efficacy by the same mechanism. PMID- 2874219 TI - Stereotyped responding by schizophrenic outpatients: cross-cultural confirmation of perseverative switching on a two-choice task. AB - Some theoretical implications from amphetamine-based models of psychosis were tested during a study of stereotyped responding by schizophrenic patients. Non institutionalized Danish schizophrenic outpatients (N = 17) and their matched normal controls were asked to guess on which side (R or L) a cross (+) would appear on a computer screen. The sequence of cross positions was random. Multiple analyses of the patients' responses revealed a significantly greater number of single alterations (RLRL), while the matched controls displayed no such tendency. Controls showed instead, significantly more right side repetitions (RRRR) and more frequent double alterations (RRLL and LLRR). The patient response sequences were similar to those seen in an earlier study by Frith and Done (Psychol Med, 13, 779-786, 1983), but some control group differences emerged. Parallels are drawn between the development of perseverative response switching in schizophrenics and predictions derived from the Lyon-Robbins theory of amphetamine-induced stereotypy. PMID- 2874220 TI - Inhibition of Trichomonas vaginalis replication by the microtubule stabilizer taxol. AB - Taxol, a plant alkaloid stabilizer of microtubules, inhibits in vitro the replication of the human pathogenic flagellate Trichomonas vaginalis in a dose dependent fashion. Micromolar concentrations of the drug induce massive assembly of microtubules, resistant to antimicrotubule agents, and block the mitosis of the protozoa at an early stage preceding the formation of the spindle fibers and the depolymerization of the axostylar microtubules. Some hypotheses involving the inactivation of the microtubule-organizing centers and the stabilization of axostylar microtubules are formulated to explain the mechanism of action of taxol. PMID- 2874221 TI - Family therapy in the treatment of severe childhood asthma. AB - Eighteen children with severe, chronic bronchial asthma were randomly divided into two groups. The families in one group received family therapy while the others served as a control group in a controlled family therapy study. Later the control families were also offered therapy in a before-after therapy design. All children were followed for 3 1/2 yr. Asthma symptoms, functional impairment and the use of drug (from diaries) were rated in ten different ways during eight months before and eight months after the family therapy. Improvement in the clinically most important variable, i.e. general pediatric assessment, was greater in the children in the family therapy group compared to the control group (p less than 0.05) Twelve children who received family therapy showed significant improvement after treatment concerning general pediatric assessment (p less than 0.01), clinical grading (p less than 0.05), peak expiratory flow (p less than 0.05), days with functional impairment/yr (p less than 0.05), no. of doses of inhaled Beta-2-agonists/month (p less than 0.01) and nights when Beta-2-agonists were inhaled (p less than 0.05). The children who only received conventional medical treatment showed no significant change in asthma symptoms. We draw the conclusion that family therapy may represent a valuable therapeutic tool in the management of severe asthma. PMID- 2874222 TI - The treatment of emotional disorders in general practice: psychological methods versus medication. AB - This paper describes three recent trials in which psychological methods were evaluated in the treatment of emotional disorders in general practice. In the first trial, brief counselling by the general practitioner was found to be as effective as anxiolytic medication, was welcomed by patients and did not increase demands on doctors' time. In the second trial (still in progress), in which treatment is aimed at emotional disorders of poor prognosis, problem solving treatment by a psychiatrist is being compared with control treatment by the G.P. The third trial evaluated an anxiety management programme provided by clinical psychologists in health centres; substantial reductions in anxiety occurred rapidly and were maintained at follow-up. PMID- 2874223 TI - Metabolic basis of adverse drug reactions. PMID- 2874224 TI - A practical guide to local cold injuries. PMID- 2874225 TI - Changes in germ cell adenylate cyclase and protein carboxyl methylase activities in rat testicular tissue during bilateral cryptorchidism and after orchidopexy. AB - Soluble Mn2+-dependent adenylate cyclase and protein carboxyl methylase are two enzymes that are primarily localized in haploid germ cels of rat testicular tissue, and both enzymes exhibit an increase in activity in association with sexual maturation. Experimental cryptorchidism (surgery at 17 days of age) in immature rats prevented the age-dependent increase in the activity of these two testicular enzymes. After orchidopexy at 34 days of age the activities of these two enzymes increased to normal control values in association with testicular growth. These observations show that biochemical markers such as soluble Mn2+ dependent adenylate cyclase and protein carboxyl methylase can be used to follow germ cell differentiation. PMID- 2874226 TI - Buspirone analogues. 2. Structure-activity relationships of aromatic imide derivatives. AB - Several analogues of the novel anxiolytic buspirone were synthesized and evaluated in vivo for tranquilizing activity and their ability to reverse neuroleptic-induced catalepsy. The in vitro binding affinities of these compounds were also examined for both the alpha 1 and dopamine D2 receptor systems. The general structure-activity relationships of this series highlight compounds 17, 21, and 32 as having anticonflict activity. Each of these structures contains the 1-(2-pyrimidinyl)piperazine moiety linked by a tetramethylene chain to a variable cyclic imide moiety. Compound 32 (4,4-dimethyl-1-[4-[4-(2-pyrimidinyl)-1 piperazinyl]butyl]-2,6- piperidinedione) was found to be equipotent with buspirone in its anxiolytic activity and was therefore selected for extensive preclinical characterization. The pharmacology of buspirone and 32 is contrasted, and the potent serotonin agonist properties of 32 are discussed with reference to its potential contribution to the anxioselective mechanism of this compound. PMID- 2874227 TI - Synthesis and beta-adrenergic receptor blocking potency of 1-(substituted amino) 3-(4-indolyloxy)propan-2-ols. AB - Although (-)-[125I]iodopindolol (IPIN) can be used to label beta-adrenergic receptors in the central nervous system in vivo, use of this ligand for receptor imaging studies in humans may be limited due to its relatively poor penetration into the brain. As a first step toward the development of radioligands for imaging studies, we report the synthesis and measurement of in vitro binding affinity to beta-receptors of a series of 1-(substituted amino)-3-(4-indolyloxy) propan-2-ol derivatives. The synthesized compounds vary widely in their lipophilicity as measured by their distribution coefficients between phosphate buffer and octanol at pH 7.4. The affinity of these compounds for beta-receptors, as measured by their inhibition of binding of IPIN to rat cortical and cerebellar membranes in vitro, ranges from 2- to 100-fold less potent than pindolol; the most potent compounds have Ki values of 2-5 nM. The radiolabeled analogues of some of these compounds may prove useful for receptor imaging studies. PMID- 2874228 TI - Antibody-dependent macrophage-mediated cytotoxicity against Entamoeba histolytica. AB - Interactions between trophozoites of Entamoeba histolytica and peritoneal exudate macrophages from unsensitised and antigen-sensitised animals were studied in vitro. Normal macrophages killed trophozoites to some extent. This killing capacity was enhanced by prior sensitisation of the animals with specific antigen. Incorporation of anti-amoebic antiserum in the amoeba-macrophage mixture greatly enhanced the killing capacity of macrophages. Fraction one (F-I) of a crude amoebic extract was most effective in enhancing the cytotoxicity of macrophages by prior sensitisation and anti-F-I serum was the most effective antiserum. The cytotoxicity-inducing capacity of the immune serum resided in the IgG but not in the IgM fraction. PMID- 2874229 TI - Ethanol drinking by vervet monkeys (Cercopithecus pygerethrus): individual responses of juvenile and adult males. AB - Unrestricted access of vervet monkeys to a palatable solution of ethanol resulted in chronic intake or abstinence. Self-selected dose averaged 4.42 g/kg body mass/day. Growth of juveniles was not grossly affected. In plasma, chronic ethanol intake was associated with lower average K and Cl values, increased gamma glutamyl transpeptidase in some adults, and higher average total cholesterol. Neither hepatic histology nor haematology were affected by chronic ethanol intake. PMID- 2874230 TI - Neuroleptics and epilepsy in mentally handicapped patients. AB - A retrospective investigation of mentally handicapped inpatients showed that neuroleptic treatment did not precipitate fits in patients without a past history of convulsions when low to moderate dosages were used. However, neuroleptic treatment did increase the number of fits in certain patients with a history of epilepsy who were receiving inadequate anticonvulsant medication or whose fits were poorly controlled despite adequate anticonvulsant levels. Guidelines for clinical practice drawn from these findings are presented. PMID- 2874231 TI - The successful treatment of the apprehensive dental patient using an interdisciplinary approach. PMID- 2874232 TI - Extinguishing conditioned responses during opiate dependence treatment turning laboratory findings into clinical procedures. AB - Former opiate addicts (even those who have remained drug-free for several months) often report symptoms of opiate withdrawal (eg. nausea, gooseflesh, etc.) and/or intense drug craving when exposed to stimuli previously associated with the act of drug injection. This phenomenon of learned or "conditioned" withdrawal/craving is widely reported and is potentially important in explaining relapse to drug use. However, no effective, clinically applicable intervention had been available to "extinguish" these conditioned phenomena. An ongoing project to develop such an intervention has revealed: Conditioned withdrawal and craving are pervasive among both methadone maintained patients (even though actual physical withdrawal is blocked) and drug-free patients even after 30 days of inpatient Therapeutic Community rehabilitation. Conditioned withdrawal and craving can be effectively extinguished in an intensive, three-week, inpatient procedure. Emotional states such as anger, depression and anxiety can elicit and exacerbate conditioned withdrawal and craving. They may also act as an integral part of a conditioned stimulus complex. The authors discuss the problems associated with turning a laboratory-based procedure into a clinical intervention. Encouraging preliminary results from an integrated treatment "package" are presented. PMID- 2874233 TI - Transformation of T-lymphoid cells by Abelson murine leukemia virus. AB - Abelson leukemia virus (A-MuLV) is an oncogenic murine retrovirus whose genome contains sequences homologous to those of a normal cellular gene, c-abl. It has been demonstrated to cause rapid transformation of several cell types, including pre-B lymphocytes, macrophages, and fibroblasts. More recently, A-MuLV has been reported to induce thymic tumors in a mouse strain (C57BL/Ka) previously thought to be resistant to disease induction. We showed that the masses occurring after intrathymic injection of the virus were composed of lymphocytes of a previously described immature T-cell phenotype. This phenotype has been defined here by flow cytometry of 10 primary tumor samples stained with antibodies to several thymocyte differentiation antigens. Hybridization of DNAs from these tumors with v-abl, immunoglobulin mu, and T-cell antigen receptor beta-chain probes confirmed the T-lymphoid, polyclonal nature of the primary tumor cells. The primary tumors were malignant, as clearly shown by reinjection into Thy-congenic host animals. Further, four Thy- in vitro cell lines derived from three tumors differed from the majority of primary tumor cells and were similar to previously described A MuLV-transformed pre-B cells. The consistent T-lymphoid phenotype exhibited by primary A-MuLV thymomas may represent one stage of normal thymocyte differentiation. PMID- 2874234 TI - Staghorn calculi: percutaneous extraction versus anatrophic nephrolithotomy. AB - We compared the procedure time, success rates, complications and recovery times for percutaneous ultrasonic lithotripsy (75 cases) and anatrophic nephrolithotomy (25) in patients with staghorn stones. Although the frequency of retained stone fragments was higher in the former group (13.3 versus 0 per cent), the shorter total procedure time (average 155.1 versus 266.5 minutes), lesser need for blood transfusions (average 2 units packed red cells in 53 per cent of the patients versus 3.5 units in 70 per cent) and narcotics (average 16 versus 33 doses), and far more rapid return to work (average 14.3 versus 54.5 days after the patients were discharged from the hospital) strongly favor percutaneous over open stone removal. PMID- 2874236 TI - Re: Orchiopexy: planned 2-stage technique. PMID- 2874235 TI - A case of simultaneous bilateral germ cell tumors arising from cryptorchid testes. AB - We report a rare case of simultaneous bilateral testicular germ cell tumors arising from uncorrected cryptorchid testes. Each side had a different histological type, which consisted of pure high grade seminoma on the left side, and teratocarcinoma with choriocarcinoma and yolk sac tumor elements in addition to seminoma on the right side. Patients with cryptorchidism are known to have a higher risk of germ cell tumors. Genetic factors also may have a role in the oncogenesis in our patient, since his older brother had had a seminoma in the left cryptorchid testis previously. Both patients had the HLA-Aw24 antigen. The characteristics of familial testicular tumors are discussed. PMID- 2874237 TI - Effect of age on cholinergic muscarinic responsiveness and receptors in the rat urinary bladder. AB - The effects of age on urinary bladder responsiveness to muscarinic agonists and on the Bmax and Kd of the binding of [3H]quinuclidinyl benzilate (QNB) to muscarinic receptors of the bladder were studied. Bladder bodies and bases were isolated from Fischer 344 rats, ages seven, 16 and 27 months. No age-dependent change in maximum KCl-elicited isotonic contractions was observed in either bladder region. The bladder base showed an age-dependent increase in the maximum contractions (Emax) elicited by muscarinic agonists. The Emax values for bladder bases from rats 27 months of age were 44 per cent, 58 per cent and 76 per cent greater than those from rats seven months of age for acetylcholine, bethanechol and oxotremorine, respectively. No such alteration in responsiveness was observed in the bladder body with age. There were no age-related changes in ED50 values for the three agonists in either bladder region. Analysis of [3H]QNB binding in the bladder base demonstrated a modest 18 per cent increase in the Bmax (fmol./mg. tissue) from seven to 16 months and a significant 39 per cent decrease from 16 to 27 months. In the bladder body, the Bmax progressively increased by 25 per cent from seven to 27 months. The Kd values of [3H]QNB did not change with age in either region. The data demonstrate that the age-related increase in the responsiveness of the bladder is regionally specific and cannot be explained by a change in the number or affinity of muscarinic receptors. PMID- 2874238 TI - Relevance of spontaneous activity to urinary bladder function: an in vitro and in vivo study. AB - The presence and functional significance (if any) of spontaneous activity in the normal urinary bladder during filling is a controversial subject. One model used by many investigators to study spontaneous activity has been isolated urinary bladder smooth muscle strips. Although spontaneous activity is a property commonly observed in isolated urinary bladder strip preparations, the in vitro whole bladder preparation (rabbit) is devoid of spontaneous activity. Additionally, under normal conditions the in vivo rabbit bladder does not display spontaneous activity during the filling phases of micturition. The present study compares the spontaneous activity of isolated smooth muscle strips, the whole bladder preparation, and the catheterized in vivo bladder (rabbit). The results are as follows: The spontaneous activity (frequency and amplitude) of isolated strips is extremely variable among strips of the same bladder. Spontaneous activity is not affected by the following specific inhibitory compounds: tetrodotoxin, atropine, phentolamine, propranolol and hexamethonium. This indicates that spontaneous activity observed in isolated strips is myogenic in nature and not dependent on the activation of specific autonomic receptors. The in vitro whole bladder preparation shows no spontaneous activity at any volume or pressure unless longitudinal tension is applied. The spontaneous activity of the whole bladder subjected to longitudinal tension is not affected by the same compounds mentioned above. Spontaneous activity of the in vivo bladder is absent at low intravesical volumes and pressures. Spontaneous activity develops upon reaching a critical pressure. However, this activity is completely inhibited by intravenous ganglionic blockade (hexamethonium). In the presence of hexamethonium, the in vivo bladder is devoid of spontaneous activity at any volume or pressure, thus the in vivo "spontaneous activity" is mediated through neuronal reflexes. It is concluded that under normal circumstances the rabbit bladder is devoid of myogenic spontaneous activity and that the spontaneous activity observed in isolated strips is directly related to longitudinal stretch. Since under normal conditions the bladder is not subjected to longitudinal stretch, the spontaneous activity observed in the isolated strip studies has little physiological significance under normal conditions, but could help explain the pathophysiology of certain dysfunctions during the filling stage of micturition. PMID- 2874239 TI - Association between abdominal wall defects and cryptorchidism. AB - To determine whether intra-abdominal pressure may have a role in the process of testicular descent in man, we reviewed retrospectively the records of all male infants who presented during a 10-year period with severe abdominal wall defects, such as gastroschisis (28), omphalocele (29) and umbilical hernia (53), and calculated the incidence of cryptorchidism in these patients. The incidence of cryptorchidism at birth and at 1 year after birth was 18 and 15 per cent, respectively, in patients with gastroschisis, 52 and 33 per cent, respectively, in those with omphalocele, and 6 and 6 per cent, respectively, in those with umbilical hernia. For all 3 disorders the incidence of cryptorchidism was higher than in documented historical controls. From these data we conclude that in male infants there is an association between these 3 abdominal wall defects and cryptorchidism. The demonstration that intra-abdominal pressure is lowered significantly by these abdominal wall defects would suggest a possible role for intra-abdominal pressure in the process of testicular descent in man. PMID- 2874240 TI - Amoebic abscess of spleen. PMID- 2874241 TI - Classification of beta-blocking agents by their inhibitory effects on phospholipase activity. AB - The inhibitory effects of beta-blocking agents against the action of phospholipase (PLase) were investigated. Using micelles of dimyristoyl (-)-alpha phosphatidylcholine (DMPC) as a substrate, myristic acid (MA) released from DMPC by PLase A2 was determined by gas chromatography. Beta-Blocking agents were divided into 4 groups depending on their inhibitory effects on PLase. Their inhibitory effects on PLase could be due to their displacing ability with Ca++ on membrane phospholipids, since Ca++ is an essential factor for the activation of PLase. PMID- 2874242 TI - [Carcinoid of the papilla of Vater-somatostatinoma--a case report]. AB - A 46-year-old woman was referred to our hospital because of liver dysfunction. She had been suffering from right hypochondralgia for two months. On admission, Laboratory data indicated extrahepatic cholestasis. Both X-ray and endoscopic examinations confirm a submucosal tumor of the papilla of Vater, and surgical diagnosis was performed. Histologically, the tumor was diagnosed as carcinoid, and a further immunohistochemical study by the PAP method using antisomatostatin serum indicated somatostatinoma. Electron microscopically, the tumor cells were found to contain numerous intracellular granules, which looked like D cells in the pancreatic islet. Somatostatinoma in the intestinal tract has been reported in only 13 cases, in only one of which was it located in the papilla of Vater. That means that, this is the second case so far. PMID- 2874243 TI - [Anti-ATLA antibody positive T cell lymphoma arising from the nasopharynx--a case report]. PMID- 2874244 TI - [The hypothalamo-hypophyseal system]. PMID- 2874245 TI - [Biological activity and function of growth hormone releasing factor]. PMID- 2874246 TI - [Secretory control of pituitary hormones--growth hormone and prolactin]. PMID- 2874247 TI - [Differential diagnosis of hyperprolactinemia]. PMID- 2874248 TI - [Pituitary hormone releasing hormone analogs and their clinical application]. PMID- 2874249 TI - Characteristic regional prevalence of HTLV-I in Shimane Prefecture. AB - Serological survey for human T-lymphotropic virus type I (HTLV-I) was performed in Shimane Prefecture, Japan, located on the coast of Japan sea. The rates of anti-adult T-cell leukemia-associated antigen-positive sera were 4.2% and 6.9% respectively for males and females. The rate increased with age, particularly in females. From the geographical point of view, the Oki Islands and a very small focus in Shimane-cho had high rates of anti-adult T-cell leukemia-associated antigen positives. Even within the Oki Islands, there was a big difference in the rate of seropositives between Dozen and Dogo which are only 10 km apart. The focus, Shimane-cho, has a population of 299. Even within a small area, there is a tendency of HTLV-I carriers to form a very narrow focus. PMID- 2874250 TI - Sporadic cases of carriers of human T-lymphotropic virus type 1 in Southeast Asia. AB - Sera obtained from 3,472 persons in Malaysia, Thailand, Philippines and Indonesia were tested for the presence of antibody to adult T-cell leukemia-associated antigen by the gelatin particle agglutination test and indirect immunofluorescence. Among these, only two seropositives were identified. One was a 30-year-old male Malaysian of Indian origin. The other was a 42-year-old female Thai who resided in Bangkok. These results suggested that the infection of human T-lymphotropic virus type 1 might not be endemic in these countries. PMID- 2874251 TI - Quantitative analysis of the local effect of skin temperature on sweating. AB - Effects of local skin temperature on sweat gland activity were analyzed quantitatively by measuring changes in the rates of thermal sweating and of drug induced sweating by local heating. The data indicates that a rise in local temperature causes an accelerated increase in the rate of sweat production, the Q10 being around 2.5 regardless of the basal sweat rate with some individual variations. Local heating apparently facilitates transmitter release at the neuroglandular junction and augments glandular responsiveness, their significances being comparable. PMID- 2874252 TI - DJ-7141, a new alpha-2 agonist with only a mild hypotensive action. AB - The pharmacological profile of a newly synthesized imidazole derivative, DJ-7141, was examined with special reference to alpha-2 adrenoceptors. In the rat vas deferens and dog mesenteric artery, DJ-7141 at concentrations over 10(-9) M selectively acted on the presynaptic alpha-2 adrenoceptors on the sympathetic nerve terminals and inhibited the contractions induced by electrical transmural stimulation. The potency of DJ-7141 was almost the same as those of clonidine and guanabenz. DJ-7141 also acted on the postsynaptic alpha-2 adrenoceptors to contract the dog saphenous vein. However, no alpha-1 agonist and antagonist actions were found at concentrations showing presynaptic alpha-2 agonist activity. In contrast to DJ-7141, clonidine produced an apparent contraction in the dog mesenteric artery, and the response was inhibited by prazosin. In urethane-anesthetized rats, clonidine at doses ranging from 0.003 mg/kg to 0.03 mg/kg produced a marked and prolonged hypotension, while DJ-7141 at such doses failed to produce a reduction of blood pressure. From these results, it is suggested that, in contrast to clonidine and other alpha-2 agonists, DJ-7141 is a unique alpha-2 agonist which shows high affinity to peripheral alpha-2 adrenoceptors but only a mild hypotensive activity. PMID- 2874253 TI - [Effect of beta-adrenoceptor agonists of the spontaneous contractility of isolated rabbit urinary bladder muscle strips]. PMID- 2874254 TI - [gamma-Glutamyl transpeptidase (gamma-GTP) activity in human semen and its source]. PMID- 2874255 TI - Pathogenicity of a non-hemagglutinating mutant strain of Fusobacterium necrophorum biovar A in mice. PMID- 2874256 TI - [Results of the conservative treatment of patients with unstable stenocardia]. AB - The results of conservative treatment were reviewed in 100 patients with unstable angina. In hospital, the condition was stabilized in 73% of patients, acute myocardial infarction developed in 24%, and fatal outcomes resulted in 7%. In the first year since the diagnosis of unstable angina was made, the incidence of acute myocardial infarction was 32%, with 14% mortality. Further prognosis for unstable angina was basically similar to that for chronic coronary heart disease. A clear-cut correlation was demonstrated between the frequency of anginal attacks, total ST displacement, the severity of coronary-bed and myocardial lesions and the incidence of acute myocardial infarction and death. PMID- 2874257 TI - [Human pathogenic gram-negative microorganisms as stimulators of the body's antitumor resistance]. PMID- 2874258 TI - [50th anniversary of the Ukrainian Republic Society of Surgeons]. PMID- 2874259 TI - [Prevention of complications in the surgical correction of cryptorchism in children]. PMID- 2874260 TI - [Lactate dehydrogenase isoenzymes in the ejaculate of men following the surgical treatment of cryptorchism--orchidopexy]. PMID- 2874261 TI - Elevation of somatostatin content, and reduction of somatostatin release by GABA in rat pancreatic islets. PMID- 2874262 TI - Theoretical approaches to D-amino acid oxidase. AB - Several substrates and roles have been proposed for D-amino acid oxidase (E.C. 1.4.3.3.); however, there is no proof that they possess the required characteristics to account for the ubiquity, large amounts and great activity of the enzyme as found in diverse cells and tissues. Based on the similar stereoposition of identically charged atoms and lateral side chain (R) with respect to the alpha-hydrogen atoms in beta-sheet conformation and in D-amino acids, it is proposed that its substrates may include several membrane-related proteins, partially in beta-sheet conformation, whose alpha-hydrogen atoms would be the real object of D-amino acid oxidase catalysis. A monooxygenase-like enzymatic activity of D-amino acid oxidase with these novel substrates is considered, for which the final products are hypothesized to be protein alpha carbon hydroxyls resulting from the incorporation of one atom of oxygen into the substrate, the other being reduced to water. Alternatively, it is also proposed that D-amino acid oxidase (and possibly other monooxygenase enzymes) would have a hydroperoxide-synthetase activity. In this case, protein alpha-carbon hydroperoxide and not water, but another reduced molecule, would be the final products. The new enzymatic performances of D-amino acid oxidase and the possible role of its potential final products in redox and other biochemical processes are discussed. PMID- 2874263 TI - [The hereditary nature of Scheuermann's disease]. PMID- 2874264 TI - [Surgical management of metastatic fractures]. PMID- 2874265 TI - [Possibilities of the prevention of cartilage damage by chemical synovectomy using osmium tetroxide]. PMID- 2874266 TI - [The role of subcapital metatarsal osteotomy in the correction of hallux valgus]. PMID- 2874267 TI - [Current surgical methods for the management of spinal injuries. Experience of the 1st International Postgraduate Course of Spinal Surgery of the Orthopedic Association (Davos, 6-11 January 1985)]. PMID- 2874268 TI - [Follow-up study of the antibiotic sensitivity and resistance of Staphylococcal strains cultured from osteomyelitis patients 1966-75 and 1976-80]. PMID- 2874269 TI - [Development and organization of accident care in our area]. PMID- 2874270 TI - [Osteomyelitis of the metatarsal sesamoid bone]. PMID- 2874271 TI - [A peroneal bone of atypical shape, simulating traumatic change]. PMID- 2874272 TI - [Hepatitis caused by salicylazosulfapyridine]. PMID- 2874273 TI - Portal-systemic encephalopathy and hepatic coma. AB - Decompensation in the cirrhotic patient is typically manifested as hepatic encephalopathy or coma. This may be precipitated by azotemia, gastrointestinal bleeding, infection, hypokalemic alkalosis, excess dietary protein, or the use of sedative, tranquilizer, or analgesic medications. The pathogenesis of hepatic encephalopathy associated with portal-systemic shunting is unknown, but theories purporting major roles for ammonia, AAAs, false neurotransmitters, and GABA have been advanced. Treatment is aimed at removing precipitating factors and eliminating nitrogenous substances from the gastrointestinal tract. PMID- 2874274 TI - Acute neurologic infections. AB - This article discusses acute bacterial, viral, toxin-mediated, and parasitic neurologic infections, emphasizing those infections that are potentially treatable, are rapidly fatal if untreated, or pose a significant risk of person to-person transmission. PMID- 2874275 TI - Progressive potential of mild cervical atypia: prospective cytological, colposcopic, and virological study. AB - A prospective study of 100 women with cytological and colposcopic evidence of mild cervical atypia consistent with cervical intraepithelial neoplasia (CIN) grade I was started in October, 1983. 26% of early preinvasive cervical lesions progressed to histologically proven CIN III. Spontaneous regression of mild cervical atypia occurred in only 11 cases, and in 4 of these CIN recurred. The overall prevalence of human papillomavirus type 16 (HPV 16) in the study group, detected by filter DNA-DNA hybridisation of a cervical cytological specimen, was 39%. However, 22 of the 26 (85%) cases of progressive disease were positive for HPV 16. Detection of HPV 16 may be a non-invasive way of identifying women at high risk of rapid progression of mild cervical atypia to CIN III. PMID- 2874276 TI - Serum relaxin in pregnancy. AB - Serum relaxin immunoactivity was measured by means of a porcine radioimmunoassay in a cross-sectional study of 302 normal singleton pregnancies. Concentrations in the third trimester were lower than in early and mid pregnancy. At term, relaxin levels in patients who went into spontaneous labour within a week of sampling were significantly lower than in those who did not. However, relaxin levels were highest during labour and fell almost to non-pregnant levels by the third postnatal day. Levels in twin pregnancies in the third trimester were higher than those in singleton pregnancies. Serial samples from 4 patients with a history of premature labour showed declining, very low levels in the only patient who subsequently had a preterm delivery. These results are compatible with the proposed roles of relaxin during pregnancy: namely, to maintain myometrial quiescence, facilitate uterine stromal remodelling during uterine growth, and promote cervical ripening at the onset of parturition. PMID- 2874277 TI - Serum relaxin and pelvic pain of pregnancy. AB - Serum relaxin immunoreactivity was measured by means of a porcine relaxin radioimmunoassay in 35 patients with severe pelvic pain and pelvic joint instability during late pregnancy. Results were compared with a control group of 368 samples obtained throughout pregnancy from normal singleton pregnancies. Most of the relaxin concentrations in the study group were above the 95% confidence limits of the median for the corresponding gestational age in the control group. The difference in relaxin levels between the study and control groups in the third trimester was highly significant. Relaxin levels in patients with pelvic pain were close to normal non-pregnant levels by the third postnatal day. The highest relaxin levels during pregnancy were found in the patients who were the most incapacitated clinically. The results suggest that there may be an association between high serum relaxin levels and pelvic pain and joint laxity during late pregnancy. PMID- 2874278 TI - Double-blind study of botulinum toxin in spasmodic torticollis. AB - In a double-blind trial in 21 patients with spasmodic torticollis botulinum-A toxin produced both subjective and objective improvement, including significant pain relief in 14 of the 16 patients presenting with pain. Side-effects were more frequently reported during placebo administration and no significant systemic adverse reactions were noted. PMID- 2874279 TI - Evaluation of serological cross-reactivity between antibodies to Plasmodium and HTLV-III/LAV. AB - Serum samples from 460 patients with existing or previous Plasmodium infections, high antimalarial antibody titres, and no apparent risk of exposure to human T lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) were assayed for HTLV-III/LAV antibody; only 1 sample, from a 21-year-old African woman, was strongly reactive by enzyme-linked immunosorbent assay (ELISA) and positive by western blot. Conversely, no sample from 100 HTLV-III/LAV-positive American homosexual men was strongly reactive for antibodies to the four Plasmodium species that infect human beings by an indirect fluorescent antibody technique, or for antibodies to Plasmodium falciparum by an ELISA technique. Thus, exposure to Plasmodium does not result in HTLV-III/LAV seropositivity, and HTLV-III/LAV antibodies are not strongly cross-reactive with malarial antigens. PMID- 2874281 TI - Safer factor VIII and IX. PMID- 2874280 TI - Unexpected mobilisation of lead during cisplatin chemotherapy. AB - During an investigation by X-ray fluorescence of platinum uptake in the kidney after chemotherapy with cisplatin, lead was found to have accumulated in the kidney in four subjects. The average kidney lead burden in one case exceeded 800 micrograms/g. Although two of the subjects had been occupationally exposed to lead, the other two had not. The tibia lead burden was also high in the two subjects in whom it was measured. The origins of this mobilised lead and the implications for cisplatin nephrotoxicity are discussed. PMID- 2874282 TI - Alcohol and haemorrhagic stroke. PMID- 2874283 TI - Attitudes to obstetric care. PMID- 2874284 TI - bcr-abl in chronic myeloid leukaemia. PMID- 2874285 TI - Sunlight and the Granstein cell. PMID- 2874286 TI - Arthritis of the hip in children. PMID- 2874287 TI - How important is rectal bleeding in the diagnosis of bowel cancer and polyps? AB - Overt bleeding from the anus is a common symptom of colorectal cancer but most frequently arises from a benign anal source. The aim of this study was to determine how successfully general practitioners and gastroenterologists could differentiate anal from colorectal sources of bleeding before full colonic investigation. 145 consecutive patients aged 40 years and over who had presented to a GP with rectal bleeding of less than 6 months' duration were referred to a specialist for total colonic investigation. The source of bleeding was diagnosed as colorectal cancer in 15 patients (7 stage A, 3 stage B) and polyps in 11. Of 63 patients in whom GPs predicted an anal source of bleeding only, 11 were ultimately found to be bleeding from a colonic or rectal source. The gastroenterologists (after rigid sigmoidoscopy) predicted an anal source of bleeding in 97, in 5 of whom the source was ultimately found to be colorectal. All patients aged over 40 who present with recent rectal bleeding should be referred for full colonic investigation. PMID- 2874288 TI - Prospective study of alcohol-related admissions in an inner-city hospital. AB - Of 2598 acute admissions to the intensive therapy unit and medical, surgical, orthopaedic, and casualty wards of a general hospital in London, 313 (12%) were definitely alcohol related. Over half (163) the patients concerned were aged between 14 and 40 and 70% (219) were male. The proportion of alcohol-related admissions varied from 7.2% for a general surgical ward up to 26.3% for the casualty overnight observation ward. Substantially higher than average rates of alcohol-related admission were seen in Irish, Scottish, and Polish patients. Of the 23 deaths in the beds under scrutiny in patients aged 17-60 years, 9 were directly attributable to acute or chronic alcohol abuse. PMID- 2874289 TI - Epithelial metaplasia and the second anatomy. PMID- 2874290 TI - From Nazi holocaust to nuclear holocaust: a lesson to learn? PMID- 2874291 TI - Mortality decline and widening social inequalities. AB - Mortality from coronary heart disease (CHD) is higher in manual than in non manual occupational classes and is higher in Scotland, Wales, and the North of England than in the South. Trends in these inequalities were examined in the light of the decline in CHD mortality in Great Britain. With the use of 1979/83 death rates as standard, mortality ratios (SMRs) for all causes, lung cancer, CHD, and cerebrovascular disease in 1979/83 were compared with SMRs in 1970-72. Despite the general fall in mortality the relative disadvantage of manual compared with non-manual classes has increased for each of these 4 cause groups. The regional differences in CHD mortality persist. Among men, in every region of Great Britain, CHD mortality has declined in non-manual classes. Only in Wales has there been an appreciable decline in CHD mortality in manual classes. Among women, lung cancer and CHD mortality have fallen in non-manual classes but have increased in manual classes. Differences in smoking between social classes are likely to be important. Other differences in behaviour may be important, but the effect of unemployment and increased income differentials should also be explored. PMID- 2874292 TI - Branhamella catarrhalis chest infections. PMID- 2874293 TI - HLA-DR in Lyme borreliosis. PMID- 2874294 TI - Deferred treatment in prostatic cancer. PMID- 2874295 TI - Recombination between factor VIII:C gene and St14 locus. PMID- 2874296 TI - Haemophilia A: two recombinations detected with probe St14. PMID- 2874297 TI - Chronic dysentery, stunting, and whipworm infestation. PMID- 2874298 TI - Coconut water. PMID- 2874299 TI - Chlamydia trachomatis and infertility. PMID- 2874300 TI - Maternal haemoglobin and pregnancy outcome. PMID- 2874301 TI - Salbutamol and pertussis. PMID- 2874302 TI - Aspirin-like analgesics and cataract. PMID- 2874303 TI - Measles exposure and the immunosuppressed child. PMID- 2874304 TI - Topical surfactant therapy for recurrent herpes simplex infection. PMID- 2874305 TI - Persistence of Coxsackie B virus-specific IgM. PMID- 2874306 TI - Thyroid protection after a nuclear reactor accident. PMID- 2874307 TI - Non-secretion of ABO antigens predisposing to infection by Neisseria meningitidis and Streptococcus pneumoniae. PMID- 2874308 TI - Epicardial monophasic action potentials. PMID- 2874309 TI - Does pertussis vaccine cause brain damage? PMID- 2874310 TI - Prediction by APACHE score. PMID- 2874311 TI - Oral manifestations in patients with AIDS or AIDS-related complex. PMID- 2874312 TI - Vertical transmission of HIV in 15-week fetus. PMID- 2874313 TI - Blood donor sera with false-positive Western blot reactions to human immunodeficiency virus. PMID- 2874314 TI - Transabdominal versus transcervical routes for chorionic villus sampling. PMID- 2874315 TI - Pretransplant lymphocyte sensitivity to methylprednisolone. PMID- 2874316 TI - Adverse reactions and the elderly. PMID- 2874317 TI - Parkinsonism, tardive dyskinesia, akathisia, and depression induced by flunarizine. PMID- 2874318 TI - Dihydropyridines and parkinsonism. PMID- 2874319 TI - Intravascular release of platelet-activating factor during atrial pacing. PMID- 2874320 TI - Totally implantable vascular access in treatment of cystic fibrosis. PMID- 2874321 TI - Ciprofloxacin and antacids. PMID- 2874322 TI - Myoglobin release, myocardial ischaemia, and heart surgery. PMID- 2874323 TI - Urinary tract infection after bladder irrigation with povidone-iodine in vaginal surgery. PMID- 2874324 TI - Leptospiras versus liberty. PMID- 2874325 TI - Lowered skin blood flow at exhaustion. PMID- 2874326 TI - Sleep apnoea in the British Isles. PMID- 2874327 TI - Immunogenicity in infants of Haemophilus influenzae type B polysaccharide in a conjugate vaccine with Neisseria meningitidis outer-membrane protein. AB - 63 children, aged 2-17 months, were given a new conjugate vaccine composed of the capsular polysaccharide of Haemophilus influenzae type b linked to a Neisseria meningitidis outer-membrane protein. Subjects under 7 months received two injections separated by 1 month, and older subjects received either one or two injections. There were no systemic reactions to this vaccine when it was given with aluminium hydroxide. A single injection of vaccine was highly immunogenic; the geometric mean serum anticapsular antibody concentrations before immunisation and 1 month later were 0.35 microgram/ml and 0.98 microgram/ml for babies of 2-3 months, 0.12 microgram/ml and 1.85 micrograms/ml for those of 4-6 months, and 0.15 microgram/ml and 4.1 micrograms/ml for those of 8-17 months (p less than or equal to 0.003 for each age group). After a second injection of vaccine, 80% and 76% of infants of 2-3 and 4-6 months, respectively, had antibody concentrations greater than 1.0 micrograms/ml. Most subjects showed evidence of IgG responses as measured by enzyme-linked immunosorbent assay. 6-12 months after immunisation, serum antibody levels had fallen (p less than 0.05) but they remained higher than those of unimmunized controls (p less than 0.001). PMID- 2874328 TI - Subclavian steal: a harmless haemodynamic phenomenon? AB - 500 patients with asymptomatic neck bruits were followed prospectively for up to 4 years with periodical standardised clinical assessments and continuous-wave carotid doppler ultrasonography, a reliable method for detecting subclavian steal. 9% of patients (45/500) had severe subclavian stenosis, and 64% of these (32/45) had a positive subclavian-steal test, with a preponderance of left-sided lesions (27/32). No patients had symptoms as a result of arm exercise during the steal test, and no patients had stroke during follow-up. Although reversed flow down one vertebral artery is relatively common in patients with generalised extracranial atherosclerosis, it is usually asymptomatic or causes, at most, vertebrobasilar transient ischaemic attacks. PMID- 2874329 TI - T lymphocytes of rheumatoid arthritis patients show augmented reactivity to a fraction of mycobacteria cross-reactive with cartilage. AB - An acetone-precipitable fraction of Mycobacterium tuberculosis cross-reacts with human cartilage. Immune responses to this antigen were assessed in 34 patients with rheumatoid arthritis, 16 patients with degenerative joint disease, and 15 healthy controls. The RA patients differed from the other two groups in having more pronounced T lymphocyte responses to the antigen; their serum antibody levels were not higher. The responses of RA patients varied with duration of disease. In the first year (7 patients) T lymphocyte reactivity was increased in the synovial exudates of affected joints but not in peripheral blood, whereas the 19 with disease of 1-10 years' duration showed high reactivity in peripheral blood; in the 8 with disease for more than 10 years, lymphocyte reactivity did not differ from that in the patients with degenerative joint disease or the healthy controls. The observation that the three groups did not differ in their responses to streptococci and a T-cell mitogen indicates that reactivity of the RA patients to the mycobacterial fraction was specific. These results raise the possibility that bacterial antigens cross-reactive with cartilage proteoglycans may be relevant to the pathogenesis of RA. PMID- 2874330 TI - Chronic hypoxaemia and decompensated erythrocytosis in cyanotic congenital heart disease. AB - Among forty adults with cyanotic congenital heart disease there was a subset of eleven patients with especially pronounced erythrocytosis, repeatedly rising haematocrit, recurring symptoms of hyperviscosity, and little or no shift of the haemoglobin/oxygen-dissociation curve. These patients were iron deficient as a result of many therapeutic phlebotomies; nevertheless their red-cell mass was comparable to that in iron-replete patients with similar, but stable, haematocrits. Iron repletion in the deficient patients resulted in rapidly increasing haematocrit and hyperviscosity. In one extreme case, erythropoiesis remained persistently iron deficient despite normal serum iron and ferritin levels. "Decompensated erythrocytosis" is an apt term for the excessive erythrocytic response and the associated phenomena. PMID- 2874331 TI - Growth factors and malignancy. PMID- 2874332 TI - Improving use of clinical resources. PMID- 2874333 TI - Pain-relief in sickle cell crisis. PMID- 2874334 TI - Dupuytren's contracture. PMID- 2874335 TI - Asthma mortality in England and Wales: evidence for a further increase, 1974-84. AB - The trend in asthma mortality has been estimated from published statistics for the years 1974-84, with account being taken of changes due to the revision of the International Classification of Diseases in 1979. Mortality rose annually by an average of 4.7% in the 5-34 year age-group (p less than 0.05), and the increased mortality since 1974 probably accounted for 408 excess deaths in the 5-64 year age-group between 1975 and 1984. No satisfactory explanation for this rise in mortality is likely until there is adequate monitoring of the prevalence and severity of asthma. PMID- 2874336 TI - Death as an option in neonatal intensive care. AB - Many paediatricians believe that there are circumstances in which infants should be allowed to die without having their lives prolonged by intensive care or surgery. During a four-year period, in a regional neonatal intensive-care unit, 75 infants were so seriously ill that withdrawal of treatment was discussed. 26 infants had severe acquired neurological damage, 26 had been born after extremely short gestation (25 weeks or less), and 23 had severe congenital abnormalities. The decision to withdraw treatment from a particular infant had to be unanimous among all the medical and nursing staff caring for that child and was based on a virtual certainty, not just of handicap, but of total incapacity--eg, microcephaly, spastic quadriplegia, and blindness. Of the 75 infants, the decision of the medical team was to withdraw treatment from 51. The parents of 47 infants accepted the decision and all these infants died. The parents of 4 infants chose continued intensive care, and 2 infants survived with disabilities. In the other 24 cases, the medical decision was to continue treatment. Of these, 17 survived and 7 died. When a thorough medical assessment had led to unanimous agreement among staff and parents that treatment should be withdrawn, its continuation on purely legal grounds is not justifiable. PMID- 2874337 TI - Scrum kidney: epidemic pyoderma caused by a nephritogenic Streptococcus pyogenes in a rugby team. AB - In December, 1984, an outbreak of pyoderma affected five scrum players in the St Thomas' Hospital rugby team. The causative organism, Streptococcus pyogenes, was acquired during a match against a team experiencing an outbreak of impetigo, and was transmitted to two front row players of another team a week later, and to two girlfriends of affected St Thomas' players a month later. The strain was M-type 49, tetracycline-resistant, and virulent. It caused salpingitis in a girlfriend and acute glomerulonephritis in one rugby player. No case of subclinical glomerulonephritis was detected in eight patients with pyoderma. Screening of the St Thomas' Hospital team revealed four further cases of non-streptococcal skin infection, with evidence for contemporaneous spread of Staphylococcus aureus. Teams should not field players with sepsis, and it may be advisable to apply a skin antiseptic to traumatised skin after the match. PMID- 2874338 TI - Cyclosporin in frequently relapsing minimal change nephrotic syndrome. PMID- 2874340 TI - Anti-STLV-IIImac reactivity in HIV seropositive individuals in Sweden. PMID- 2874339 TI - Night-time rioprostil versus ranitidine in duodenal ulcer healing. PMID- 2874341 TI - Vertical transmission of human immunodeficiency virus. PMID- 2874343 TI - Depression in the elderly. PMID- 2874342 TI - Malnutrition and HIV infection in children in the Central African Republic. PMID- 2874344 TI - Origin of abnormal magnetic resonance imaging signal in multiple sclerosis. PMID- 2874345 TI - Respiratory mucus. PMID- 2874346 TI - Radioactive iodine for thyrotoxicosis. PMID- 2874347 TI - Primary hyperoxaluria type I: oxalate and glycolate unsuitable for prenatal diagnosis. PMID- 2874348 TI - Cross-resistance and imipenem. PMID- 2874349 TI - Dilutional hyponatraemia masquerading as subarachnoid haemorrhage in patient on hydrochlorothiazide/amiloride/timolol combined drug. PMID- 2874350 TI - Molecular biology of osteogenesis imperfecta. PMID- 2874351 TI - Bile acids and gastric acid. PMID- 2874352 TI - Hypomelanosis of Ito and chromosomal mosaicism in fibroblasts. PMID- 2874353 TI - Polyunsaturated fat and coronary heart disease. PMID- 2874354 TI - Reduced platelet mitogenic activity in myeloproliferative disorders. PMID- 2874355 TI - Life expectancy, truth, and the ABPI. PMID- 2874356 TI - Alternative medicine. PMID- 2874357 TI - Secure accommodation in psychiatric hospitals. PMID- 2874358 TI - Grand multiple pregnancies and demand for neonatal intensive care. PMID- 2874359 TI - Replication of clinical trials. PMID- 2874360 TI - Lisuride infusion pump for Parkinson's disease. PMID- 2874361 TI - Psychosis and the lisuride pump. PMID- 2874362 TI - Prevention of Clostridium difficile outbreaks in hospitals. PMID- 2874363 TI - First-trimester prediction in fetus at risk for myotonic dystrophy. PMID- 2874364 TI - Chance that individual in Duchenne family is recombinant. PMID- 2874365 TI - Measurement of central motor conduction in multiple sclerosis by magnetic brain stimulation. AB - Central motor conduction time (CMCT) to abductor digiti minimi was measured in 18 healthy subjects and in 15 patients with multiple sclerosis. A novel percutaneous magnetic stimulator was used to stimulate the motor cortex painlessly and CMCT was calculated by subtracting the onset latency of muscle responses obtained by electrical stimulation over the C7/T1 interspace from that obtained from stimulation over the scalp. In healthy subjects CMCT was 6.0 +/- 0.76 ms. In multiple sclerosis patients with pyramidal signs in the arms, CMCT was almost always prolonged, the longest conduction time being 39 ms. In 10 patients CMCT was prolonged despite normal strength in the muscle. PMID- 2874367 TI - Beta-cell dysfunction, rather than insulin insensitivity, is the primary defect in familial type 2 diabetes. AB - Continuous infusion of glucose with model assessment was used to measure glucose tolerance, beta-cell function, and insulin sensitivity in 154 first-degree relatives of 55 patients with type-2 diabetes. The plasma glucose achieved at 1 h was normally distributed in normal control subjects, but 31 (20%) of relatives of type-2 diabetics had values above the normal distribution mean +2 SD. Insulin secretion, assessed from the first or second phase plasma-C-peptide responses, was significantly lower in the glucose-intolerant relatives than in normoglycaemic relatives of similar sex, age, and obesity. beta-cell function, estimated by means of model analysis, was severely impaired in the glucose intolerant relatives but was not impaired in the normoglycaemic relatives (geometric mean 41% and 109% of normal beta-cell response, respectively). Reduced beta-cell function was found with all degrees of glucose intolerance, whereas only the more severely hyperglycaemic relatives had impaired insulin sensitivity. This suggests that the primary defect in familial type-2 diabetes is beta-cell dysfunction. PMID- 2874366 TI - Relative importance of antibiotic and improved clearance in topical treatment of chronic mucopurulent rhinosinusitis. A controlled study. AB - 50 patients with chronic mucopurulent rhinosinusitis were randomly allocated to treatment with nasal sprays of dexamethasone, tramazoline, and neomycin, dexamethasone and tramazoline with no antibiotic, or matched placebo (propellant alone) four times daily to both nostrils for 2 weeks. The patients were assessed in a double-blind manner for symptomatic response and improvement in nasal mucociliary clearance, nasal airway resistance, sinus radiographs, and intranasal bacteriology and appearance. Both active preparations (with antibiotic 14 of 20 patients responded; without antibiotic 12 of 20 patients responded) were more effective than the placebo (2 of 10 patients responded). There was no significant difference in response between the active preparations with and without antibiotic. Thus, in treatment of chronic mucopurulent rhinosinusitis, reduction of the inflammatory response and decongestion make topical antibiotic unnecessary, probably by allowing host clearance mechanisms to recover. PMID- 2874368 TI - Bloated irritable bowel syndrome defined by dynamic 99mTc bran scan. AB - The motility of the ileocaecal region of the gut was studied in 10 women with irritable bowel syndrome (IBS) and bloating and in 8 normal women. Bran labelled with 37 MBq 99mTc was administered after fasting, and a dynamic scan was done after a standard meal 3 h later. Time-activity curves were plotted for the ileum and caecum. In controls, ileal emptying was faster, peak % counts in the caecum were higher, and ileocaecal clearance was greater than in those with IBS. The profound motor dysfunction seen in those with IBS may account for their symptoms, and the "bran scan" could become an important diagnostic aid. PMID- 2874369 TI - Effect of activated charcoal on hypercholesterolaemia. AB - Seven patients with hypercholesterolaemia were treated for 4 weeks with activated charcoal at a dose of 8 g three times a day. Plasma total cholesterol and LDL cholesterol decreased by 25% and 41%, respectively, whereas HDL-cholesterol increased by 8%. Side-effects were negligible. PMID- 2874370 TI - Intake of marine fat, rich in (n-3)-polyunsaturated fatty acids, may increase birthweight by prolonging gestation. AB - Birthweights in the Faroe Islands are among the highest in the world. Compared with Denmark, the average birthweight of liveborn singleton infants of primiparous mothers is 194 g higher, and a substantial part of this difference seems to be attributable to longer gestation. Prostaglandins play an important part in the timing of parturition in human beings. Dietary (n-3)-polyunsaturated fatty acids (PUFA) in high amounts influence endogenous prostaglandin metabolism. Owing to the large consumption of marine fat, the average intake of (n-3)-PUFA in the Faroes by far exceeds that in Denmark. The hypothesis proposed is that dietary (n-3)-PUFA in high amounts prolong gestation in human beings by interfering with uterine production of prostaglandins, possibly by inhibiting the production of dienoic prostaglandins, primarily PGF2 alpha and PGE2, which are mediators of uterine contractions and cervical ripening. PMID- 2874371 TI - Atrial natriuretic peptide. PMID- 2874372 TI - Reinfection with influenza. PMID- 2874374 TI - Advice to the aspiring physician. PMID- 2874373 TI - Third-nerve headache. PMID- 2874375 TI - Cyclophosphamide for paraquat poisoning? PMID- 2874376 TI - Transhiatal oesophagectomy without thoracotomy. PMID- 2874377 TI - Ranking of laboratory tests by consensus analysis. AB - A new analytical technique (consensus analysis) was devised to assess the performance of laboratory tests that are commonly used to monitor the acute and chronic phases of inflammatory disease. On thirty-one tests carried out monthly for 7 months in seventeen patients with rheumatoid arthritis, the consensus analysis procedure ranked plasma viscosity and erythrocyte sedimentation rate in a tie for first place. Measurement of the acute-phase serum protein orosomucoid ranked third. Consensus analysis has the potential to reduce laboratory costs by identifying the most useful tests; it also promises to be helpful in the design of new laboratory tests that are more sensitive and specific. PMID- 2874378 TI - Outbreak of legionellosis in a community. Report of an ad-hoc committee. AB - Of 33 patients infected in an outbreak of legionellosis in Glasgow in 1984, 26 lived in the Dennistoun district and the remainder either worked in or visited there. There were three main clusters of cases, the onset of illness being in early and mid June in two clusters and early September in the third. Most patients were not severely ill, but 1 patient died. The likely source of infection was a cooling tower from which Legionella pneumophila serogroup 1 was isolated. Strains indistinguishable from the cooling-tower strain were isolated from 2 of the patients. Cases occurred downwind of this cooling tower up to a distance of 1700 m. It is suggested that airborne infection with L pneumophila may extend further from the source than has hitherto been recognised. PMID- 2874379 TI - Home parenteral nutrition in the United Kingdom and Ireland. AB - Between January, 1977, and March, 1986, 200 patients were registered as receiving home parenteral nutrition (HPN) in the UK and the Republic of Ireland. Although 28 centres contributed case-reports, 75% of the cases were registered by 7 centres. Most patients started treatment between the ages of 10 and 40 years, a reflection of the high incidence of Crohn's disease during these decades. The three main indications for HPN were Crohn's disease (90 patients), mesenteric vascular disease (27), and extensive small-bowel resection for volvulus or other benign enteric disease (14). 85 patients required treatment for less than 1 year and 17 have been on treatment for more than 2 years. Patients whose indication for HPN was a primary intestinal disease had a better quality of life than did those in whom the intestinal failure was secondary to a systemic disorder. Of the 108 patients who have completed treatment 56 have been able to resume enteral nutrition through adaptation of the remaining bowel, or closure of a fistula. 34 have died, 19 as a consequence of the underlying disease and 10 of complications of treatment. The incidence of catheter-related sepsis varied between 0.2 and 0.9 episodes per year of treatment (overall 0.35) depending on the length of experience of the supervising centre. PMID- 2874380 TI - Do climbs to extreme altitude cause brain damage? PMID- 2874381 TI - Chlamydia trachomatis in the upper female genital tract with negative cervical culture. PMID- 2874383 TI - Relation between breast tumour growth rate and metastatic potential. PMID- 2874382 TI - Synvinolin in hypercholesterolaemia. PMID- 2874384 TI - False-negative finding on chorionic villus sampling. PMID- 2874385 TI - How many families will be informative for prenatal prediction of cystic fibrosis with multiple linked DNA probes? PMID- 2874386 TI - DNA typing to avoid need for prenatal diagnosis of cystic fibrosis. PMID- 2874387 TI - Pre-conception counselling for parents who have a child with cystic fibrosis. PMID- 2874388 TI - Bone marrow toxicity of cyclosporin in a kidney transplant patient. PMID- 2874389 TI - Hydergine and reversibility of cyclosporin nephrotoxicity. PMID- 2874390 TI - Bone marrow transplantation in childhood lymphoblastic leukaemia. PMID- 2874391 TI - Renin and the heart. PMID- 2874392 TI - Beta-blockade and prevention of ventricular fibrillation after myocardial infarction. PMID- 2874393 TI - Isolation of HTLV-I from cerebrospinal fluid of a patient with myelopathy. PMID- 2874394 TI - HIV infection in renal allograft recipients. PMID- 2874395 TI - Should lesbians give blood? PMID- 2874396 TI - Cot deaths and the Sheffield Score. PMID- 2874397 TI - Effects of medical research on life expectancy. PMID- 2874398 TI - Urea/creatinine ratio and gastrointestinal haemorrhage. PMID- 2874399 TI - Campylobacter pyloridis, urease, and gastric ulcers. PMID- 2874400 TI - Causes of acute cardiotoxic effects of beta-adrenergic antagonist overdose. PMID- 2874401 TI - Prevention of cervical cancer. PMID- 2874402 TI - Membrane stabilising activity and inhibition of human sperm motility. PMID- 2874403 TI - Nature of atrial natriuretic peptide in plasma from patients with congestive heart failure. PMID- 2874404 TI - Screening for congenital hypothyroidism. PMID- 2874405 TI - Screening for risk of delivery of a hypothyroid baby. PMID- 2874406 TI - Cell-dose effect in circulating stem-cell autografting. PMID- 2874407 TI - Viruses in acute childhood encephalopathy. PMID- 2874408 TI - Avoiding ifosfamide/mesna encephalopathy. PMID- 2874409 TI - Patient-triggered ventilation in the newborn. PMID- 2874410 TI - Court not bound to accept test of competent medical practice in deciding whether contraceptive counselling is negligent. PMID- 2874411 TI - Mechanism of action of adjuvant chemotherapy in early breast cancer. AB - The relation between tumour oestrogen and progesterone receptor status, menstrual status, relapse-free survival, and overall survival was analysed in 411 patients with early breast cancer randomised to receive either postoperative adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF) or no additional treatment (control). Prolongation of time to recurrence and survival was seen predominantly in premenopausal patients; these effects were seen only with tumours positive for steroid receptors, particularly progesterone. Chemotherapy led to permanent amenorrhoea in 61% of premenopausal patients. The therapeutic effects of chemotherapy were seen only when CMF induced permanent amenorrhoea in premenopausal patients. These findings support the hypothesis that the effect of adjuvant chemotherapy in early breast cancer may be mediated by ovarian suppression. PMID- 2874412 TI - Effect of passive smoking on birth-weight. AB - 500 consecutive Danish women who had full-term babies were interviewed on the third or fourth day post partum and asked about smoking in all household members. Exposure to smoking by the mother was found to reduce birth-weight, and indirect or passive exposure to smoking by the father had nearly as large (66%) an effect. On average, birth-weight was reduced by 120 g per pack of cigarettes (or cigar/pipe equivalent) smoked per day by the father. This relation remained statistically significant after controlling for mother's age, parity, alcohol and tobacco consumption during pregnancy, illness during pregnancy, and social class and sex of the baby. The effect of passive smoking was greatest in the lower social classes. PMID- 2874413 TI - Protective effect of naturally acquired homotypic and heterotypic rotavirus antibodies. AB - To assess serotype specificity of immune resistance to rotavirus gastroenteritis, the relation between pre-existing neutralising antibodies to homotypic and heterotypic rotaviruses and protection against infection or clinical illness was investigated. The subjects were 44 orphans exposed once or twice to consecutive outbreaks of gastroenteritis due to type 3 rotavirus in an orphanage in Sapporo. Sera were collected throughout these outbreaks and the serum levels of neutralising antibodies against four different serotypes of group A human rotavirus were measured before and after the outbreaks. Protection against rotavirus gastroenteritis seemed to be serotype specific and to be related to levels of antibody against homotypic virus. A neutralising antibody level of 1/128 or greater seemed to be protective. The protective effect was of short duration, which was probably the explanation for recurrent attacks of gastroenteritis due to a rotavirus of the same serotype. Seroconversions or concomitant antibody responses to type 1 or 4 rotavirus in most children with type 3 rotavirus infection suggested that immunity to heterotypic virus can be induced by a rotavirus vaccine. PMID- 2874414 TI - Defective brain microtubule assembly in Alzheimer's disease. AB - Brains obtained within 2-4 hours post mortem and histopathologically confirmed for Alzheimer's disease and non-Alzheimer brains from age-matched controls were examined for in-vitro assembly of microtubules and neurofilaments. Microtubule assembly was observed only in control but not in Alzheimer brains, and neurofilaments were obtained from both types of brain. The microtubule-associated protein tau, which stimulates assembly of microtubules from tubulin, was abnormally phosphorylated in Alzheimer but not in control brain microtubule preparations. Alzheimer brains did not show the presence of any inhibitor of microtubule assembly or any abnormality of tubulin. DEAE-dextran, a polycation which mimics tau in stimulating microtubule assembly, induced the assembly of microtubules in Alzheimer brain. Tubulin from both normal and Alzheimer brains was labelled on western blots by a monoclonal antibody to the tyrosinylated carboxy-terminal epitope of alpha tubulin. These studies suggest that in Alzheimer's disease tubulin can be assembled into brain microtubules, but the process is defective, probably because of abnormal phosphorylation of tau. This post-translational alteration of tau might be the cause of the neurofibrillary abnormality in Alzheimer's disease. PMID- 2874415 TI - Levodopa in restless legs. AB - The effectiveness of levodopa in the treatment of restless legs was assessed in a double-blind trial. 20 patients were given levodopa and lactose on alternate days. Treatment was continued until patients stated a preference for one of the treatments or were unable to discriminate between the two. 17 patients preferred levodopa, none lactose, and 3 were unable to discriminate. The 17 patients who responded to levodopa reported complete relief. PMID- 2874416 TI - Does angiotensin-II protect against strokes? AB - In the Medical Research Council trial for the treatment of mild hypertension, bendrofluazide showed an unexpected and sizeable benefit compared with propranolol in the reduction of stroke. It is suggested that this difference reflects the opposing actions of these drugs on the renin-angiotensin system. The hypothesis that angiotensin-II protects the distal smaller cerebral vessels, which are the usual site of vessel rupture in intracerebral haemorrhage, indicates that long-term benefit of angiotensin-converting-enzyme inhibitors in the treatment of hypertension cannot be assumed. PMID- 2874417 TI - Prevention and control of iodine deficiency disorders. PMID- 2874418 TI - Britain needs a food and health policy: the Government must face its duty. PMID- 2874419 TI - Prognosis in myelodysplasia. PMID- 2874420 TI - Chronic atrophic candidosis. PMID- 2874421 TI - Mammillary fistula. PMID- 2874422 TI - ARDS: a clinical view. PMID- 2874423 TI - The spectrum of hepatotoxicity due to drugs. AB - Drugs in common use can cause toxic effects on the liver which can mimic almost every naturally occurring liver disease in man. Drugs can have direct (metabolite related) toxic effects; they can also cause deposition of microvesicular fat in hepatocytes; or they can provoke reactions resembling acute alcoholic hepatitis (phospholipidosis) or acute viral hepatitis. Hepatotoxicity can also be part of a general hypersensitivity reaction, or hepatic fibrosis or cholestasis can predominate. Drugs can lead to almost any type of vascular disease in the liver and to benign and malignant tumours. PMID- 2874424 TI - Brain lesions detected by magnetic resonance imaging in mild and severe head injuries. AB - 50 patients were studied by magnetic resonance imaging (MRI) within one week of a head injury. Abnormalities indicating primary brain damage were found in 46 patients, almost twice as many as with computed tomography. Cortical contusions were the most common finding, irrespective of the effect of injury on the level of consciousness. Intracerebral lesions were seen only in patients who had lost consciousness and were present in 29 of 42 patients whose consciousness was still impaired on arrival at hospital. Lesions in the deep white-matter of the cerebral hemispheres were seen in 15 patients; they were significantly more frequent in patients in coma but were also seen in patients who had lost consciousness for no more than 5 min. The findings indicate that lesions in the cerebral hemispheres may be the primary factor in traumatic unconsciousness. MRI studies may also clarify the sequelae of head injuries. PMID- 2874425 TI - Continuing education: what techniques are effective? PMID- 2874426 TI - Vitamin A supplementation and child mortality. PMID- 2874427 TI - Is maintenance therapy necessary for acute lymphoblastic leukaemia? PMID- 2874428 TI - Placental drainage and fetomaternal transfusion. PMID- 2874429 TI - Total lymphoid irradiation in multiple sclerosis. PMID- 2874430 TI - Shoulder-tip pain in chemical peritonitis. PMID- 2874431 TI - Ultrasound biparietal diameter in spina bifida. PMID- 2874432 TI - AIDS and Hodgkin's disease. PMID- 2874433 TI - Antibodies to simian immunodeficiency virus in African green monkeys in Africa in 1957-62. PMID- 2874434 TI - Plasma atrial natriuretic peptide in severe thermal injury. PMID- 2874435 TI - Prevention of postoperative deep vein thrombosis. PMID- 2874436 TI - Relation between 131I therapy for thyrotoxicosis and development of thyroid carcinoma. PMID- 2874437 TI - Cerebral perfusion during cardiac surgery. PMID- 2874438 TI - Effect of interferon on psoriasis. PMID- 2874440 TI - Management of non-respiratory tuberculosis. PMID- 2874439 TI - Lithium prophylaxis inhibits choline transport in post-mortem brain. PMID- 2874441 TI - Protein browning and diabetic complications. PMID- 2874442 TI - May hypocarbia cause ischaemic brain damage in the preterm infant? PMID- 2874443 TI - Placentas and transmissible dementias. PMID- 2874444 TI - Salt-sensitive hypertension in West Africans: an uncoupling of the renal sodium dopamine relation. PMID- 2874445 TI - Captopril and blood glucose. PMID- 2874446 TI - Double-blind trial of herbal slimming pill. PMID- 2874447 TI - High-voltage shock treatment for snake bite. PMID- 2874448 TI - Acid-base effects of "non-systemic" antacids. PMID- 2874449 TI - Multiple sclerosis and wool. PMID- 2874450 TI - Side-effects of flunarizine. PMID- 2874451 TI - Baking soda baths for aquagenic pruritus. PMID- 2874452 TI - Food incentives and clinic attendance. PMID- 2874453 TI - Treatment of hydroxocobalamin-resistant methylmalonic acidaemia with adenosylcobalamin. PMID- 2874454 TI - Latex agglutination test for Legionella antibody. PMID- 2874455 TI - Retroperitoneal fibrosis and bromocriptine. PMID- 2874456 TI - A simple screening test for medium-chain acyl CoA dehydrogenase deficiency. PMID- 2874457 TI - Nifedipine-induced parotitis. PMID- 2874458 TI - Trace metal contamination of albumin solutions used for plasma exchange. PMID- 2874459 TI - Surfactants and enzymes in respiratory mucus. PMID- 2874460 TI - Thrombotic events after intravenous immunoglobulin. PMID- 2874461 TI - The effects of reserpine and haloperidol on tyrosine hydroxylase activity in the brains of aged rats. AB - Many neurotransmitter systems appear to be altered with aging. The effects of aging on the regulation of tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of catecholamines in the brain has been examined. The endogenous basal activity of tyrosine hydroxylase was lower in the hypothalamus of 24 month old Fisher 344 rats than in the hypothalamus of 3 month old or 6 month old animals. There was no difference in the basal activity of tyrosine hydroxylase in the locus ceruleus, frontal cortex, hippocampus, substantia nigra, or the striatum of rats of ages 3 months, 6 months and 24 months. Tyrosine hydroxylase activity was increased in the striatum of 3 month old (60%) and 6 month old (28%) rats after treatment with haloperidol or reserpine, whereas no change in enzyme activity followed administration of these drugs to 24 month old animals. In conclusion, increases in tyrosine hydroxylase activity in the brain that normally occur in the striatum of 3 month old rats after haloperidol or reserpine treatment are significantly decreased in 6 month old rats and not apparent in 24 month old rats. PMID- 2874462 TI - Co-cultivation of astroglial enriched cultures from striatum and neuronal containing cultures from substantia nigra. AB - A co-cultivation system was developed with neuron-containing (neuron-specific enolase (NSE) positive) primary cultures from the substantia nigra of 15 to 17 day old embryonic rats which were grown 1 mm apart from astroglial-enriched (glial fibrillary acidic protein (GFAp) positive) primary cultures from the striatum of neonatal rats. The astroglial cells went through a morphological differentiation with extension of processes after co-cultivation with the immunohistochemically-identified neuronal cells. The astroglial-enriched striatum cultures showed a higher active uptake of 3H-L-glutamate after co-cultivation for one week, compared to control cultures from striatum. Vmax (nmol X mg protein-1 X min-1 X was 58.4 +/- 8.3 after co-cultivation and 37.2 +/- 6.3 for control cultures. The glutamine synthetase (GS) activity was slightly increased after co cultivation. The validity and specificity of the results were ensured. The data suggest that astroglial cells in a primary culture are influenced by co cultivation with fetal neuron containing cultures resulting in morphological differentiation, and increases in 3H-L-glutamate uptake and GS activity. PMID- 2874463 TI - Neuroendocrine mechanisms of stress ulceration: focus on thyrotropin-releasing hormone (TRH). AB - It is generally accepted that stress ulceration, a multifactorial or pluricausal gastrointestinal disorder, may be the result of mechanistic interrelationships between mucosal, vascular, hormonal and neurogenic factors. The relative importance of each of these independent mechanisms remains unclear. This minireview represents an attempt to interpret many recent studies on certain neurogenic mechanisms and to integrate these observations into the existing body of knowledge. A variety of in vitro techniques and animal models to manipulate actual structures, organ systems, and certain well-defined hormonal influences have been utilized. The peripheral studies have followed, for the most part, the established observation that the stomach is under reciprocal control by sympathetic inhibitory and parasympathetic excitatory autonomic fibers. As a result, several autonomic adrenergic neurotransmitter substances have been found to promote mucosal resistance. Some of these include dopamine, epinephrine, and norepinephrine. Others in contrast, appear to promote vulnerability of the mucosa, and of these, the most well-studied include acetylcholine and histamine. PMID- 2874464 TI - Actions of cimetidine and ranitidine at some cholinergic sites: implications in toxicology and anesthesia. AB - Cimetidine and ranitidine are specific and potent H2-receptor antagonists widely used in the effective therapy of peptic ulcer disease. The drugs also possess other pharmacological properties unrelated to H2-receptor antagonism. More recently large experimental doses of cimetidine or ranitidine were found to have anticholinesterase, ganglion blocking and neuromuscular blocking activities. Actions of the drugs at such cholinergic sites may account for some of their clinically documented adverse effects. The toxicological implications of these findings including the potential for drug interactions to occur, especially during some anesthetic procedures, are discussed. PMID- 2874465 TI - Iontophoretic studies on rat hippocampus with some novel GABA antagonists. AB - Twelve substances which appear to be GABA antagonists, judging by their ability to reverse the inhibitory effect of GABA on 35S-TBPS binding to rat brain membranes, were tested iontophoretically on population spikes in the rat hippocampus. Eight of them, including seven which completely reversed the inhibitory action of GABA on 35S-TBPS binding, caused a marked enhancement of population spikes, with slow onset and long duration and they antagonized the inhibition of population spikes by GABA. These effects were similar to those produced by bicuculline. Electrophysiologically, the most potent of the "complete reversers" were bathophenanthroline disulfonate and brucine. In vitro, amoxapine and brucine most effectively reversed the inhibitory action of GABA on 35S-TBPS binding. Of the five substances which only partly reversed the inhibitory effect of GABA on 35S-TBPS binding, four depressed the population spikes and potentiated the inhibitory action of GABA. The fifth "partial reverser", pipazethate, potently increased the population spikes, like the "complete reversers". Although other interpretations are possible the results are consistent with the existence of several GABA-A receptor types in brain, only some of which are blocked by certain partial reversers. PMID- 2874466 TI - Lack of effect of dynorphin on consummatory behaviors in obese and normal rats. AB - The possible role of dynorphin, an endogenous opioid peptide, in the regulation of appetite was studied in male genetically-obese (Zucker) rats and their litter mates of normal weight. Eighteen pairs were divided into 3 treatment groups: control, acutely dynorphin-treated (5 mg/rat), and implanted with Alzet mini osmotic pumps containing 2 mg dynorphin to be delivered at a rate of 10 micrograms/hr. Body weights and food and water consumption were determined daily for 7 days. Body weights were not significantly changed from initial values for any treatment group. Food and water consumption per 24 hours were generally the same for obese rats and their normal littermates, but in terms of consumption per 100 g body weight, the obese rats generally consumed less food and water. Neither acute nor continuous dynorphin administration affected consummatory levels. PMID- 2874467 TI - Patients with Alzheimer's disease show an increased content of 15 Kdalton somatostatin precursor and a lowered level of tetradecapeptide in their cerebrospinal fluid. AB - The relative proportions of both somatostatin-14 and its precursors somatostatin 28 and the 15 Kdalton prosomatostatin were evaluated by radioimmunoassay in the cerebrospinal fluid of patients with Alzheimer's disease. It was observed that the patients have a lowered content in the tetradecapeptide somatostatin while they exhibit a significant increase in unprocessed 15 Kda precursor. These results indicate that these patients possess impaired processing mechanisms which may be responsible for the lowered content in mature somatostatin-14. These observations may provide a valuable test for the ante-mortem diagnosis of the disease. They are discussed in connection with others suggesting that Alzheimer's patients may be selectively altered in their somatostatinergic neurones of their cerebral cortex (Morrison et al. (1985) Nature 314, 90-92. Roberts et al. (1985) Nature 314, 92-94). PMID- 2874468 TI - Acute and subchronic effects of Rimcazole (BW 234U), a potential antipsychotic drug, on A9 and A10 dopamine neurons in the rat. AB - The effects of acute and subchronic Rimcazole administration on A9 and A10 dopamine (DA) neurons were examined using extracellular single cell recording techniques. Intravenous injections of Rimcazole did not prevent or reverse the inhibition of firing rates of DA cells produced by DA agonist apomorphine (APO). Single intraperitoneal injection of Rimcazole decreased the number of spontaneously active DA cells in A10, but not in A9; it had no effect on the firing rate of DA neurons in either A9 or A10. Following prolonged administration of Rimcazole, 25 mg/kg/day for 28 days, there was a significant increase in the number of spontaneously active A10 DA neurons, but not A9 DA cells. The firing rate of both A9 and A10 DA cells decreased significantly following prolonged Rimcazole administration; however, the firing pattern of these cells did not change. In addition, chronic Rimcazole did not affect the ID50 of APO for DA neurons. These results suggest that Rimcazole has an indirect effect on DA neurons with a relative selectivity for A10 DA cells; it does not exhibit pharmacological profiles of previously reported antipsychotic drugs. PMID- 2874469 TI - A study of the effects of buspirone, BMY 13805, and 1-PP on dopaminergic metabolism in the nucleus accumbens using in vivo voltammetry in freely moving rats. AB - The effects of buspirone, a buspirone analogue (BMY 13805) and a buspirone metabolite (1-PP) on dopaminergic metabolism in the nucleus accumbens were investigated using in vivo voltammetry. Differential pulse voltammetry coupled with electrochemically pretreated carbon fiber electrodes was used to provide a continuous and selective measure of the 3,4-dihydroxyphenylacetic acid (DOPAC). An implanted micromanipulator enabled the use of freely moving animals. Buspirone injections induced a marked and rapid increase of the DOPAC peak in the nucleus accumbens. Buspirone was 10 times more potent when injected subcutaneously than intraperitoneally. BMY 13805 and 1-PP were without effect on dopaminergic metabolism in the nucleus accumbens. In conclusion, the anxiolytic properties of these drugs and their effects on dopaminergic metabolism do not appear related. PMID- 2874470 TI - CGS 10746B: an atypical antipsychotic candidate that selectively decreases dopamine release at behaviorally effective doses. AB - CGS 10746B, a benzothiadiazepine, has a behavioral profile in mice and monkeys similar to the atypical antipsychotic clozapine. Unlike clozapine, CGS 10746B suppresses dopamine neuron firing rates and, when administered at behaviorally effective doses by the oral or intraperitoneal route, decreases neostriatal dopamine release without changing dopamine metabolism or occupying D2 receptors. CGS 10746B is the first atypical antipsychotic candidate that selectively decreases dopamine release. PMID- 2874471 TI - Presynaptic dopaminergic modulation of cortical input to the striatum. PMID- 2874472 TI - Identification of the tridecapeptide dynorphin B (rimorphin) within perikarya of rat duodenum. AB - Using an immunofluorescence microscopic staining technique, the opioid peptide dynorphin B (rimorphin) was revealed within neuronal cell bodies of the rat duodenum. Dynorphin B immunoreactive perikarya were revealed in the myenteric and submucousal plexus as well as in the longitudinal muscle layer. They were large in diameter and round in shape and they contained a large round nucleus. Because no dynorphin B immunofluorescent nerve fibre and terminal could be noted it might be that dynorphin B is further cleaved by proteases into the bioactive opioid pentapeptide Leu-enkephalin and dynorphin B(6-13). These findings might also indicate that dynorphin B is processed within duodenal perikarya and that it has important physiological roles in the rat duodenum. PMID- 2874473 TI - Glafenine-associated hepatic injury. Analysis of 38 cases and review of the literature. AB - Glafenine was associated with hepatic injury in 38 cases. The causal relationship was assessed on the basis of the temporal relationship with drug use, course and exclusion of other causes. In 27 cases a causal relationship was considered likely, i.e. 'probable' (12 cases) or 'possible' (15 cases), whereas in 11 cases it was either unlikely or unclassifiable. In both the 'probable' and 'possible' groups 60-70% of individuals were women. Jaundice was present in three-quarters of cases in both groups. Eosinophilia was more frequent in the group of 'probable' cases, and this group had the highest case-fatality rate (42%). Onset varied from 2 days (after a rechallenge) to 8 months, but most cases appeared between 2 weeks and 4 months after starting therapy. Histology in 22 cases showed a predominantly hepatocellular pattern, varying from spotty panlobular necrosis, centrilobular and (sub)massive necrosis (acute pattern) to fibrosis and cirrhosis (chronic pattern). The chemical structure of glafenine and the clinicopathological pattern it induces resemble that of cinchophen. The incidence is unknown. Either metabolic idiosyncrasy or an immunoallergic mechanism seems to be responsible. PMID- 2874474 TI - Fourier transform infrared studies of an active proton transport pump. PMID- 2874475 TI - Reconstitution of an H+ translocator, the "uncoupling protein" from brown adipose tissue mitochondria, in phospholipid vesicles. PMID- 2874476 TI - Experiments with the nematocysts of Cyanea capillata. PMID- 2874477 TI - Uracil nucleotide synthesis in a human breast cancer cell line (MCF-7) and in two drug-resistant sublines that contain increased levels of enzymes of the de novo pyrimidine pathway. AB - Cultured wild-type MCF-7 human breast cancer cells and two MCF-7 sublines that overproduce enzymes of the de novo pyrimidine biosynthetic pathway were compared with regard to: rate of de novo biosynthesis of uracil nucleotides, sensitivity of the de novo and salvage pathways to the concentration of intracellular uracil nucleotides, and potential of exogenous uridine at concentrations equivalent to plasma levels to affect de novo pyrimidine biosynthesis. The PALAR MCF-7 subline, which is resistant to N-(phosphonacetyl)-L-aspartate and has 5.2 times the activity of the first de novo enzyme as the wild-type MCF-7 cells, synthesizes uracil nucleotides via the de novo pathway at a rate that is 5.8 times that of the wild type MCF-7 cells. The PYRR MCF-7 subline, which is resistant to pyrazofurin and has 15.1 times the activity of orotate phosphoribosyltransferase as the wild-type MCF-7 cells, synthesizes uracil nucleotides via the de novo pathway at a rate that is 1.4 times that of wild-type MCF-7 cells. These results are consistent with carbamyl phosphate synthetase being the rate-controlling step of de novo pyrimidine biosynthesis. In the presence of exogenous uridine at concentrations equivalent to that found in plasma (4.4-8.6 microM), the uracil nucleotide pool of wild-type MCF-7 cells was expanded by 20% and de novo synthesis was inhibited by 55%. Incubation of PALAR MCF-7 cells with uridine at concentrations between 7.3 and 16.8 microM caused a 40% increase in the uracil nucleotide pool and a 30% inhibition of de novo synthesis. De novo synthesis of uracil nucleotides in PYRR MCF-7 cells was not affected by a greater than 10-fold increase in the uracil nucleotide pool. Salvage of [14C] uridine was inhibited by an expanded uracil nucleotide pool in the wild-type and PYRR MCF-7 cells but was not inhibited in the PALAR MCF-7 cell line. These results demonstrate that, although the overproduced enzymes exhibit substrate affinities and specificities in cell-free preparations similar to those of the wild-type enzymes, in intact cells the resistant cell lines exhibit marked differences in the control of de novo and salvage pyrimidine biosynthetic pathways by intracellular uracil nucleotides. PMID- 2874478 TI - Differential polyadenylation pattern of ovalbumin precursor RNAs during development. AB - The expression of the ovalbumin gene encoding for the major hen oviduct protein slows down with age. Analysis of Northern blots of electrophoretically separated total and poly(A) + RNA from oviducts of hens of different age with an ovalbumin specific probe (nick-translated 9.5 kb ovalbumin gene DNA cloned into pBR322) revealed that the largest high molecular weight ovalbumin RNA precursor (7.9 kb band, representing the putative primary transcript of the ovalbumin gene) was most intense if total RNA from non-egg-laying old hen oviduct was checked as compared to that from egg-laying mature animals. On the other side, the 7.9 kb RNA precursor band was readily detected in the poly(A) + RNA from mature hen oviduct whereas it was invisible in the old hen oviduct poly(A) + RNA fraction. The lack of detection of the 7.9 kb RNA species within the poly(A) + RNA fraction and its increased concentration within the total oviduct RNA, both from old animals, suggest that age-dependent impairment of ovalbumin mRNA processing may be caused by altered polyadenylation of distinct RNA precursors. PMID- 2874479 TI - In vitro synthesis and processing of a maize chloroplast transcript encoded by the ribulose 1,5-bisphosphate carboxylase large subunit gene. AB - The large subunit gene (rbcL) of ribulose 1,5-bisphosphate carboxylase was transcribed in vitro by using maize and pea chloroplast extracts and a cloned plastid DNA template containing 172 base pairs (bp) of the maize rbcL protein coding region and 791 bp of upstream sequences. Three major in vitro RNA species were synthesized which correspond to in vivo maize rbcL RNAs with 5' termini positioned 300, 100 to 105, and 63 nucleotides upstream of the protein-coding region. A deletion of 109 bp, including the "-300" 5' end (the 5' end at position -300), depressed all rbcL transcription in vitro. A plasmid DNA containing this 109-bp fragment was sufficient to direct correct transcription initiation in vitro. A cloned template, containing 191 bp of plastid DNA which includes the 105 and -63 rbcL termini, did not support transcription in vitro. Exogenously added -300 RNA could be converted to the -63 transcript by maize chloroplast extract. These results established that the -300 RNA is the primary maize rbcL transcript, the -63 RNA is a processed form of the -300 transcript, and synthesis of the -105 RNA is dependent on the -300 region. The promoter for the maize rbcL gene is located within the 109 bp flanking the -300 site. Mutagenesis of the 109 bp chloroplast sequence 11 bp upstream of the -300 transcription initiation site reduced rbcL promoter activity in vitro. PMID- 2874480 TI - Neuroblastoma cells express c-sis and produce a transforming growth factor antigenically related to the platelet-derived growth factor. AB - Mouse neuroblastoma Neuro-2A cells produce transforming growth factors during exponential growth in a defined hormone-free medium, which, on Bio-Gel columns in 1 M HAc, elute at a molecular size of 15 to 20 kilodaltons (kDa). These neuroblastoma-derived transforming growth factors have strong mitogenic activity, but they do not compete with epidermal growth factor for receptor binding (E. J. J. van Zoelen, D. R. Twardzik, T. M. J. van Oostwaard, P. T. van der Saag, S. W. de Laat, and G. J. Todaro, Proc. Natl. Acad. Sci. U.S.A. 81:4085-4089, 1984). In this study approximately 80% of the mitogenic activity was immunoprecipitated by antibodies raised against platelet-derived growth factor (PDGF). Immunoblotting indicated a true molecular size of 32 kDa for this PDGF-like growth factor. Analysis of poly(A)+ RNA from Neuro-2A cells demonstrated the expression of the c sis oncogene in this cell line, whereas in vitro translation of the RNA yielded a 20-kDa protein recognized by anti-PDGF antibodies. Separation by reverse-phase high-pressure liquid chromatography demonstrated the presence of two distinct mitogenic activities in neuroblastoma-derived transforming growth factor preparations, one of which is antigenically related to PDGF. Both activities had the ability to induce anchorage-independent growth in normal rat kidney cells, both in the presence and in the absence of epidermal growth factor. It is concluded that Neuro-2A cells express c-sis with concomitant production and secretion of a PDGF-like growth factor, which plays a role in the induction of phenotypic transformation on normal rat kidney cells. PMID- 2874481 TI - Regulated expression of a chimeric histone gene introduced into mouse fibroblasts. AB - The regulated expression of a mouse histone gene was studied by DNA-mediated gene transfer. A chimeric H3 histone gene was constructed by fusing the 5' and 3' portions of two different mouse H3 histone genes. Transfection of the chimeric gene into mouse fibroblasts resulted in the production of chimeric mRNA at levels nearly equal to that of the total endogenous H3 histone mRNAs. Most chimeric RNA transcripts had correct 5' and 3' termini, and the chimeric mRNA was translated into an H3.1 protein that accumulated in the nucleus of the transfected cells. Expression of the chimeric gene was studied under several conditions in which the rate of transcription and the stability of endogenous H3 transcripts change. Chimeric mRNA levels were regulated in parallel with endogenous H3 mRNAs, suggesting that cis-acting regulatory sequences lie within or near individual histone genes. In addition to correctly initiated and terminated chimeric mRNA, we also detected a novel H3 transcript containing an additional 250 bases at the 3' end. Surprisingly, the longer transcript is polyadenylated and accumulates in the cytoplasm. PMID- 2874482 TI - Amplification of the gene for histidyl-tRNA synthetase in histidinol-resistant Chinese hamster ovary cells. AB - Histidinol-resistant (HisOHR) mutants with up to a 30-fold increase in histidyl tRNA synthetase activity have been isolated by stepwise adaptation of wild-type Chinese hamster ovary (CHO) cells to increasing amounts of histidinol in the medium. Immunoprecipitation of [35S]methionine-labeled cell lysates with antibodies to histidyl-tRNA synthetase showed increased synthesis of the enzyme in histidinol-resistant cells. The histidinol-resistant cell lines had an increase in translatable polyadenylated mRNA for histidyl-tRNA synthetase. A cDNA for CHO histidyl-tRNA synthetase has been cloned, using these histidyl-tRNA synthetase-overproducing mutants as the source of mRNA. Southern blot analysis of wild-type and histidinol-resistant cells with this cDNA showed that the histidyl tRNA synthetase DNA bands were amplified in the resistant cells. These HisOHR cells owed their resistance to histidinol to amplification of the gene for histidyl-tRNA synthetase. PMID- 2874483 TI - Chromosomal assignment and trans regulation of the tyrosine aminotransferase structural gene in hepatoma hybrid cells. AB - The structural gene encoding liver-specific tyrosine aminotransferase (TAT; EC 2.6.1.5) was assigned to mouse chromosome 8 by screening a series of hybrid cell lines for retention of murine Tat-1 gene sequences by genomic Southern blotting. This assignment demonstrated that the Tat-1 structural gene was not syntenic with Tse-1, a chromosome 11-linked locus that negatively regulates TAT expression in trans (A. M. Killary and R. E. K. Fournier, Cell 38:523-534, 1984). We also showed that the fibroblast Tat-1 gene was systematically activated in hepatoma X fibroblast hybrids retaining fibroblast chromosomes 8 in the absence of chromosome 11 but was extinguished in cells retaining both fibroblast chromosomes. Thus, the TAT structural genes of both parental cell types were coordinately regulated in the intertypic hybrids, and the TAT phenotype of the cells was determined by the presence or absence of fibroblast Tse-1. PMID- 2874484 TI - Entamoeba histolytica as a commensal intestinal parasite in homosexual men. AB - Entamoeba histolytica is considered to be an uncommon, imported organism in the United Kingdom and in many parts of North America, but recent attention has been drawn to the possibility of sexual transmission of this parasite among homosexual men. To determine the prevalence and clinical importance of enteric parasitic infections in men attending a clinic in London for the treatment of sexually transmitted diseases, we studied 354 randomly selected patients who provided a single stool sample that was examined for E. histolytica and other intestinal parasites. Forty-five of the 225 homosexual patients (20 percent) were infected with E. histolytica, but no such infections were found among the 129 heterosexual subjects (P less than 0.0001). With the use of isoenzyme electrophoresis, 34 of the 45 E. histolytica isolates were classified according to zymodeme. All were Zymodeme I or III, which are considered to be nonpathogenic. There was no correlation between the presence of E. histolytica and gastrointestinal symptoms. These findings suggest that E. histolytica is a common commensal in the homosexual population and that, in the absence of evidence of invasive disease, treatment of persons passing cysts of the organism may have little practical benefit. PMID- 2874485 TI - Barrett's esophagus. PMID- 2874486 TI - Isoenzyme patterns and pathogenicity in amebic infection. PMID- 2874487 TI - Treatment of homosexual men infected with Entamoeba histolytica. PMID- 2874488 TI - Undescended testes--is surgery necessary? PMID- 2874489 TI - An overview of the clinical rationale for advancing gender-related psychopharmacology and drug abuse research. PMID- 2874490 TI - Gender as a factor in treating the elderly. PMID- 2874491 TI - Biochemistry. New role for transfer RNA. PMID- 2874492 TI - Mediation of thalamic sensory input by both NMDA receptors and non-NMDA receptors. AB - Excitatory amino acids such as L-glutamate and L-aspartate are well established as neurotransmitter candidates in the mammalian central nervous system, and three types of receptor for these substances have been proposed, characterized by the agonists N-methyl-D-aspartate (NMDA), kainate and quisqualate. All these receptors have been suggested to have synaptic roles in excitatory transmission in the brain. Here I demonstrate that NMDA receptors play a crucial role in the observed response of ventrobasal thalamus (VB) neurones to natural stimulation of somatosensory afferents, but do not appear to be responsible for the short latency excitation seen on electrical stimulation of the afferents which is apparently mediated by excitatory amino-acid receptors of the non-NMDA type. This result indicates an involvement of NMDA and non-NMDA receptors in the responses of VB neurones to stimulation of somatosensory somatosensory afferents, depending on the mode of stimulation of the pathway. PMID- 2874493 TI - Frequency-dependent involvement of NMDA receptors in the hippocampus: a novel synaptic mechanism. AB - Acidic amino acids, such as l-glutamate, are believed to be excitatory neurotransmitters in the mammalian brain and exert effects on several different receptors named after the selective agonists kainate, quisqualate and N-methyl-D aspartate (NMDA). The first two receptors collectively termed non-NMDA receptors, have been implicated in the mediation of synaptic transmission in many excitatory pathways in the central nervous system (CNS), whereas NMDA receptors, with few exceptions do not appear to be involved; this is typified in the hippocampus where there is a high density of NMDA receptors yet selective NMDA receptor antagonists, such as D-2-amino-5-phosphonovalerate (APV), do not affect synaptic potentials. NMDA receptors have, however, been shown to be involved in long-term potentiation (LTP) in the hippocampus, a form of synaptic plasticity which may be involved in learning and memory. NMDA receptors have also been found to contribute to epileptiform activity in this region. We now describe how NMDA receptors can participate during high-frequency synaptic transmission in the hippocampus, their involvement during low-frequency transmission being greatly suppressed by Mg2+. A frequency dependent alleviation of this blockade provides a novel synaptic mechanism whereby a single neurotransmitter can transmit very different information depending on the temporal nature of the input. This mechanism could account for the involvement of NMDA receptors in the initiation of LPT and their contribution, in part, to epileptic activity. PMID- 2874494 TI - A mouse locus at which transcription from both DNA strands produces mRNAs complementary at their 3' ends. AB - The organization and large size of the mammalian cell genome allows spatial separation of different transcription units. In those cases where more than one species of messenger are synthesized from the same cellular DNA sequence, they have been found to be generated from transcription proceeding in the same direction. These mRNAs always share regions of homology and can differ from one another as a result of differential processing (splicing and/or polyadenylation) or alternative initiation. In contrast, complementary mRNAs transcribed from opposite strands of the same cellular DNA sequence have not previously been observed. Here we have identified a region of mouse DNA at which processed mRNAs from two adjacent convergent transcription units overlap by 133 base pairs (bp) at their 3'-untranslated ends. One of the transcription units appears to encode a second mRNA which does not contain this overlapping region. This represents the first description of the natural occurrence of processed mammalian cell mRNAs transcribed from opposite strands of the same DNA sequence. The implications of these complementary regions in normal gene regulation are discussed in the context of the finding that the artificial introduction into cells of DNA constructs synthesizing anti-sense RNAs complementary to regions of mRNA transcribed from a chromosomal gene, can inhibit the gene's activity, presumably by the formation of double-stranded RNA. PMID- 2874495 TI - Overlapping transcription units in the dopa decarboxylase region of Drosophila. AB - The many examples of overlap in the genes of various viruses and bacteria illustrate that the parsimonious utilization of the coding capacity of DNA is relatively common amongst prokaryotes. The recent discovery of a pupal cuticle gene within an intron of the completely unrelated Gart locus in Drosophila shows that overlapping transcription units also exist in higher organisms. However, the prevalence of such phenomena in unknown. We report here a quite different situation of overlap between the 3' termini of a pair of convergent transcription units in another region of the Drosophila genome. This 88-base-pair (bp) genomic region encodes the 3' terminus of the messenger RNA for the enzyme dopa decarboxylase (Ddc) and, in opposite orientation, the 3' terminus of the adjacent gene whose function is unknown. An analysis of the temporal and spatial distribution of the two transcripts within the organism shows that high levels of both transcripts are never concordant. However, within the testes, where the 3' transcript is maximally expressed, low levels of Ddc transcript were detected. This result raises the possibility that a hybrid molecule involving the two transcripts forms in vivo or that transcription interference occurs, with concomitant regulatory implications. PMID- 2874496 TI - Diversity of haematopoietic stem cell growth from a uniform population of cells. PMID- 2874497 TI - The long and the short of long-term memory--a molecular framework. AB - A single learning event initiates several memory processes with different time courses of retention. While short term memory involves covalent modification of pre-existing proteins, the finding that long-term memory requires the expression, during learning, of additional genes, makes it possible to analyse in molecular terms the induction and retention of long-term memory. PMID- 2874498 TI - Retinal ganglion cells lose response to laminin with maturation. AB - The decisive role played by adhesive interactions between neuronal processes and the culture substrate in determining the form and extent of neurite outgrowth in vitro has greatly influenced ideas about the mechanisms of axonal growth and guidance in the vertebrate nervous system. These studies have also helped to identify adhesive molecules that might be involved in guiding axonal growth in vivo. One candidate molecule is laminin, a major glycoprotein of basal laminae which has been shown to induce a wide variety of embryonic neurones to extend neurites in culture. Moreover, laminin is found in large amounts in injured nerves that can successfully regenerate but is absent from nerves where regeneration fails. However, it is unclear to what extent the mechanisms that regulate axonal regeneration also operate in the embryo when axon outgrowth is initiated. Here we have examined the substrate requirements for neurite outgrowth in vitro by chick embryo retinal ganglion cells, the only cells in the retina to send axons to the brain. We show that while retinal ganglion cells from embryonic day 6 (E6) chicks extend profuse neurites on laminin, those from E11 do not, although they retain the ability to extend neurites on astrocytes via a laminin independent mechanism. This represents the first evidence that central nervous system neurones may undergo a change in their substrate requirements for neurite outgrowth as they mature. PMID- 2874499 TI - Autoreceptors and alpha 2-adrenoceptors at the serotonergic axons of rabbit brain cortex. AB - Slices of the rabbit occipito-parietal cortex were preincubated with 3H-serotonin and then superfused and stimulated electrically (2 min at 3 Hz). In the absence of drugs, the stimulation-evoked overflow of tritium was approximately 3% of the tritium content of the tissue. Unlabelled serotonin and 5-carboxamido-tryptamine, when administered in the presence of 6-nitroquipazine, reduced the evoked overflow of tritium. Their effects were antagonized by metitepin (apparent pA2 value 8.1) and (+/-)-cyanopindolol (apparent pA2 value 6.4). Metitepin, but not cyanopindolol, increased evoked tritium overflow; the effect of metitepin was greater in the presence than in the absence of nitroquipazine. The evoked overflow of tritium was also depressed by clonidine, an effect antagonized by idazoxan (apparent pA2 value 7.0) but not by prazosin. Phenylephrine caused a decrease only at high concentrations that simultaneously accelerated basal tritium efflux. Prazosin and idazoxan did not change evoked tritium overflow, and phentolamine increased it significantly only when administered in the presence of (+)-oxaprotiline. Rauwolscine produced an inhibition that was prevented by metitepin. It is concluded that the serotonergic axons of the rabbit occipitoparietal cortex possess presynaptic, release-inhibiting serotonin autoreceptors and alpha 2-adrenoceptors. The receptors appear to receive an input of endogenous serotonin and, to a lesser extent, noradrenaline, under the conditions of these in vitro experiments. PMID- 2874500 TI - Modulation by fenoldopam (SKF 82526) and bromocriptine of the electrically evoked release of vasopressin from the rat neurohypophysis. Effects of dopamine depletion. AB - Single neurointermediate lobes were fixed by their stalks to a platinum wire electrode and incubated in Krebs-bicarbonate solution. Vasopressin release into the medium was determined by a radioimmunoassay. Vasopressin secretion was increased by electrical stimulation (15 Hz, 10 s trains with 10 s intervals for 10 min). Fenoldopam (SKF 82526) had a dual effect on vasopressin release, 30 nM decreasing (by 30%) and 3 microM increasing (by 32%) the evoked vasopressin secretion. The facilitatory effect of fenoldopam was antagonized in a concentration-dependent manner by flupenthixol but not by sulpiride. Sulpiride (1 microM) prevented the inhibitory effect of fenoldopam (30 microM). After pretreatment of the rats with the dopamine depleting agent, Ro4-1284 (2 mg/kg i.p. 1 h before the experiments), the evoked vasopressin release was decreased by 21% and the inhibitory effect of fenoldopam disappeared, but the facilitatory effect of fenoldopam was already seen at 30 nM. Similarly, bromocriptine (1-10 microM) decreased the evoked vasopressin release from untreated neurointermediate lobes by 30-40% but increased the vasopressin release by 30% after pretreatment with Ro4-1284. The present findings further support the concept that vasopressin from the neurohypophysis is modulated by dopaminergic mechanisms. Facilitatory effects are mediated via D 1 and inhibition via D 2 receptors. The presence of endogenous dopamine seems to be necessary for the inhibitory effects to occur. PMID- 2874501 TI - Direct inhibition of tyrosine hydroxylase from PC-12 cells by catechol derivatives. AB - Several drugs with a catechol moiety were studied for their potency to inhibit tyrosine hydroxylase (TH) from PC-12 cells in vitro. When the natural compounds tested were compared, dopamine, norepinephrine and 2(3,4-dihydroxyphenyl)-ethanol (DOPET) were most effective (IC50 between 1.4 and 3.6 microM with 0.5 microM 6(R,S)-L-erythro-5,6,7,8-tetrahydrobiopterin as cofactor). 3,4 Dihydroxyphenylalanine (DOPA; IC50: 35 microM) and 3,4-dihydroxyphenylacetic acid (DOPAC; IC50: 180 microM were less potent inhibitors. Among the synthetic drugs possessing catechol moiety, isoproterenol, (+/-)-2-amino-6,7-dihydroxy-1,2,3,4 tetrahydronaphthalene (6,7-ADTN) and (+/-)-2-dimethylamino-6,7-dihydroxy tetrahydronaphthalene (TL-99) had the same inhibitory effects as the natural catecholamines (IC50 between 1.6 and 3.9 microM), whereas the apomorphine derivatives and 2,3,4,5-tetrahydro-1-phenyl-1 H-3-benzazepine-7,8-diol (SKF 38393) were even more potent (IC50: 0.5-0.8 microM). These results demonstrate that natural catechols and certain drugs (e.g. 6,7-ADTN, TL-99, SKF 38393) are more effective direct blockers of tyrosine hydroxylase than generally assumed provided appropriate assay conditions are used. In the case of dopamine and norepinephrine, these findings suggest a reevaluation of their role for feedback control of tyrosine hydroxylase in vivo. PMID- 2874502 TI - Biochemical and pharmacological effects of fluperlapine on noradrenaline and acetylcholine systems in some rodent, bovine and crustacean preparations. AB - Fluperlapine was compared with clozapine, chlorpromazine, haloperidol and imipramine regarding its effects on some cholinergic and noradrenergic animal systems. Fluperlapine and clozapine showed the most pronounced anticholinergic effects. Fluperlapine was equipotent with clozapine in displacing [3H]-QNB from muscarinic receptors of the calf cerebral cortex (IC50 about 15 nM). In the mydriasis test in the mouse and in the crayfish hindgut bioassay the differences between fluperlapine and clozapine were small. Like the other antischizophrenic drugs tested, fluperlapine displayed a marked affinity for alpha 1-adrenoceptors (calf cerebral cortex: IC50 about 10 nM) but a negligible affinity for alpha 2 adrenoceptors in the same tissue. Only clozapine showed a weak affinity for the latter receptor type. Fluperlapine was as effective as imipramine in antagonizing tetrabenazine-induced ptosis in the rat, the anti-ptotic effect remaining constant after up to ten daily drug administrations. Still, imipramine was stronger than fluperlapine as an inhibitor of the accumulation of [3H] noradrenaline ([3H]-NA) in rat cerebral cortex slices. Fluperlapine's effects on the spontaneous and the electrically-induced release of [3H]-NA from rat cerebral cortex slices, with and without protriptyline, showed it to be an inhibitor of the reuptake of NA. The results indicate that the pharmacological profile of fluperlapine is similar to that of clozapine, with additional antidepressant properties. PMID- 2874503 TI - The beta 1-adrenoceptor antagonist CGP 20712 A unmasks beta 2-adrenoceptors activated by (-)-adrenaline in rat sinoatrial node. AB - The role of sinoatrial beta 1- and beta 2-adrenoceptors mediating positive chronotropic effects of (-)-adrenaline and (-)-noradrenaline was investigated in rat right atria. Concentration effect curves for (-)-adrenaline, but not for (-) noradrenaline, became biphasic in the presence of the beta 1-adrenoceptor antagonist CGP 20712 A. The curves for (-)-adrenaline in the presence of 300 nmol/l CGP 20712 A (equivalent to 1,000 times its KB, KB = 0.3 nmol/l for beta 1 adrenoceptors) comprise a high-sensitivity component that saturates at 1/4 of maximum effect, and a low sensitivity component. The high-sensitivity component is blocked by the beta 2-adrenoceptor-selective antagonist ICI 118,551. These results are consistent with an involvement in the rat of both beta 1 adrenoceptors (to a major extent) and beta 2-adrenoceptors [only at high (-) adrenaline concentrations] in the positive chronotropic effects of (-) adrenaline. (-)-Noradrenaline appears to activate mostly rat sinoatrial beta 1 adrenoceptors. PMID- 2874505 TI - Paradoxical effects of benzodiazepines. PMID- 2874504 TI - The significance of beta-adrenoceptor down regulation in the desipramine action in the forced swimming test. AB - The present studies were undertaken to clarify whether central beta-adrenoceptor down regulation is responsible for the greater effect of chronic treatment with desipramine (DMI) compared with acute treatment in the forced swimming test in rats. Repetitive administration of DMI activated the rat behaviour pattern and consequently reduced the duration of immobility. The degree of activation depended on the length of treatment, i.e. no effect when given in a single dose, moderate effect when given subchronically (3 doses) and marked activation after chronic (31 doses) treatment. Chronic treatment with DMI also produced a decrease in 3H-dihydroalprenolol (3H-DHA) binding site in the cerebral cortex. Acute stimulation of brain beta-adrenoceptors by intracerebroventricular (i.c.v.) isoprenaline significantly, though partially, attenuated the behavioural effect of chronic DMI by beta 1-adrenoceptor-related mechanisms. Similarly, chronic i.c.v. co-administration of atenolol or practolol, beta 1-adrenoceptor antagonists, together with DMI attenuated both beta-adrenoceptor down regulation and the behavioural activation by chronic DMI. On the other hand, chronic i.c.v. administration of isoprenaline, supposedly leading to down regulation of beta adrenoceptors, facilitated the activating behavioural effect of DMI, as a single dose became effective. Changes, however, in 3H-DHA binding parameters in the cerebral cortex were not observed after chronic isoprenaline. These results suggest that down regulation of beta-adrenoceptors in brain is responsible, at least in part, for the marked activatory effect of chronic DMI in the forced swimming test, possibly by reducing an inhibitory function of beta 1-adrenoceptor mediated mechanisms. PMID- 2874506 TI - [Dependence and abstinence symptoms in the use of benzodiazepines]. PMID- 2874507 TI - [Treatment and course of schizophrenic psychoses over a decade. Disease course and predictors]. PMID- 2874508 TI - Chronic active hepatitis and periarteritis nodosa in a patient with co-occurrence of circulatory hepatitis Bs antigen and anti-HBs. PMID- 2874509 TI - Immunoelectron microscopic demonstration of Thy-1 antigen on the surfaces of mesangial cells in the rat glomerulus. AB - Mesangial cells of F344 rats degenerated and then disappeared within 2 days after the intravenous administration of rabbit antirat thymocyte serum (ATS). Rabbit IgG and rat C3 were identified in the mesangium in the rat glomeruli. To establish the glomerular binding site of ATS administered intravenously into rats, one kidney of each rat given ATS intravenously 12 h earlier was perfused ex vivo through the renal artery with peroxidase-labeled antirabbit IgG followed by sequential glutaraldehyde and diaminobenzidine perfusions to minimize the ultrastructural damage. The other kidney was removed before the perfusion for histologic study to examine the glomerular injury. The rabbit IgG identified by peroxidase-reaction product was present diffusely in the glomerular mesangium when viewed by light microscopy and exclusively on the surfaces of most mesangial cells by electron microscopy. Immunofluorescence microscopy showed rabbit IgG essentially in the mesangium, and electron microscopy revealed the degeneration of mesangial cells in the kidneys that had been removed before the surgical perfusion. However, no histological abnormalities were found in the kidneys from control rats given ATS absorbed with rat thymocytes. The present study showed that the intravenous administration of ATS into rats induced the extensive mesangial cell damage by the binding of ATS to Thy-1 antigens on the mesangial cells. PMID- 2874510 TI - Effects of neonatal administration of diazepam and lorazepam on performance of adolescent rats in tests of anxiety, aggression, learning and convulsions. AB - Male offspring of hooded Lister rats were fostered at birth and allocated to experimental litters of eight, in which at least one rat was allocated to every treatment group. Vehicle control, diazepam (1 or 10 mg/kg) or lorazepam (0.25 or 2.5 mg/kg) were administered daily from postnatal day 1-21. Rats were tested undrugged at adolescence (days 35-41). Neonatal treatment with diazepam (10 mg/kg) or lorazepam (2.5 mg/kg) tended to increase active social interaction, perhaps indicative of an anxiolytic effect. These treatments also increased unpunished licking, but were without effect on punished drinking. When the experimental rats were resident in their home-cages the effect of neonatal treatment with diazepam (1 mg/kg) was to increase the number of offensive behaviors directed at an untreated intruder. In contrast, neonatal treatment with lorazepam (2.5 mg/kg) increased the frequency and duration of submissions to the intruder. When the rats that had been treated neonatally were intruding into the territory of an untreated resident rat, diazepam treatment (10 mg/kg) increased wrestling, whereas lorazepam (0.25 mg/kg) decreased sniffing and kicking the resident. The neonatal treatments did not affect acquisition or short-term retention of a passive avoidance response, but the re-entry latencies indicated poorer long-term retention by diazepam-treated rats. The neonatal treatments did not change the threshold for convulsions to pentylenetetrazole. PMID- 2874511 TI - [Acute renal failure associated with drugs or iodinated contrast media. Results of a cooperative multicentric study by the Nephrology Society]. AB - During a one-year period, drug-associated acute renal failure (ARF) was prospectively recorded in 398 patients, registered in 58 french nephrology Units. Drugs involved were primarily antibiotics, mainly aminoglycosides, glafenine, non steroidal antiinflammatory drugs and contrast media. Hypersensitivity reactions were reported in 69 patients. Renal biopsy, performed in 81 instances, showed acute tubular necrosis in 42 and acute interstitial nephritis in 20 patients. Hypotension, sodium depletion and/or cardiac failure were predisposing factors in 198 cases. Fifty patients died, 251 recovered fully or regained previous renal function, and in 93 permanent renal damage remained. Advanced age, oliguria, severe ARF, and preexisting cardiac, hepatic or renal insufficiency were poor prognostic factors. Prevention of drug-associated ARF should be directed to high risk patients, particularly those receiving aminoglycosides and contrast media. PMID- 2874512 TI - Primary astroglial cultures. A biochemical and functional evaluation. PMID- 2874513 TI - Neuroendocrine heart and hypothalamus. AB - Data on the endocrine heart--neurosecretory cells of heart, producing coronary dilatory, metabolically active glycopeptides with physico-chemical and biological properties similar to those of previously discovered cardioactive hypothalamic neurohormones--are summarized. Heart hormones participate in both local and distant regulation of heart metabolism and function. Formation and action of these heart hormones is closely related to hypothalamic cardioactive neurohormones K, C, and G and their protein precursors. Neurohormones from heart and hypothalamus comprise a system of neurohumoral connections between these two organs. A possible role of APUD cells in the generation of a number of heart peptides and glycopeptides exerting hormonal activity is discussed. PMID- 2874514 TI - Immunocytochemical characterization of the A15 A5 transplantable brain tumour model in vivo. AB - A comparative immunocytochemical study was carried out on intracerebral and extracranial gliomas of the rat produced by intracerebral injection of low (10th) and high (40th) in vitro passages of neoplastic glial cells. The cells injected were a neoplastic astrocytic clone-A15 A5-derived from a mixed glioma induced transplacentally by N-ethyl-N-nitrosourea (ENU) in a BD-IX rat. An inverse relationship was seen between the expression of the astrocytic markers glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) at low and high passage: GFAP decreased with increasing passage while GS increased. The distribution of vimentin, the major cytoskeletal component of immature glia, was constant, irrespective of passage--a feature consistent with previous in vitro findings. The expression of laminin by both reactive and neoplastic astrocytes increased with increasing passage, while high magnification examination revealed the presence of the glycoprotein fibronectin on the cell-surfaces of A15 A5 derived tumour cells. Both neoplastic and reactive astrocytes expressed S-100 protein with a higher proportion of positive cells in extracranial tumours. Occasional cells, probably actively phagocytizing populations of reactive astrocytes and macrophages, were positive for alpha-1-antitrypsin. None of the neoplastic cells expressed the oligodendrocyte marker carbonic anhydrase II. This immunocytochemical study supports previous morphological findings in differences in differentiation between the cells of tumours produced by high and low passage cells. PMID- 2874515 TI - Effect of somatostatin and dopaminergic agents on bovine pituitary phosphodiesterase activity. AB - The effects of somatostatin and dopaminergic agents on pituitary cyclic nucleotide phosphodiesterases that had been partially purified through DEAE cellulose column chromatography were studied. Somatostatin, L-dopa, dopamine and CB-154(2-bromo-alpha-ergocriptine) competitively inhibited the pituitary cyclic AMP phosphodiesterase activity, especially that of the low Km enzyme. This inhibition was most potent in the case of somatostatin and CB-154. PMID- 2874516 TI - Involvement of endogenous somatostatin in the regulation of thyrotroph secretion during acute and chronic changes in diet. AB - The aim of this study was to investigate the involvement of somatostatin (SRIF) in the thyrotroph adaptation to nutritional changes. For this purpose, we studied the effects of passive immunization with SRIF antiserum (A-SRIF) on the reduced basal TSH secretion in rats starved for 72 h and on the plasma TSH surge following carbohydrate (CHO) refeeding. This latter experiment was performed at two different times of the day in order to elucidate whether SRIF may participate in the regulation of the plasma TSH circadian rhythm. In chronically catheterized rats, we observed that A-SRIF injection induced a similar pattern of plasma TSH rise over a sampling period of 5 1/2 h in both fed and rats starved for 72 h (3 way analysis of variance). In morning experiments, CHO refeeding or A-SRIF injection elicited a significant rise in plasma TSH. The amplitude and duration of the response was proportional to the injected dose. In evening experiments, although basal TSH values were significantly lower than those observed in the morning ones, maximal plasma TSH values after A-SRIF injection were not significantly different. At both times of the day, association of refeeding and A SRIF injection did not stimulate TSH further than either refeeding alone or A SRIF alone. In conclusion, our data suggest that SRIF cannot account for the differences in serum TSH levels between fed and starved rats; is not responsible for the diurnal difference in basal serum TSH in starved rats, and seems to be involved in the TSH response to refeeding. PMID- 2874517 TI - Effect of morphine and morphine-like analgesics on susceptibility to seizures in mice. AB - In mice, the influence of small (analgesic range) doses of morphine, fentanyl, meperidine and pentazocine on the thresholds for seizures induced by electroshock and pentetrazole was studied. The antinociceptive ED50 was determined against writhing induced by acetic acid or morphine (0.43 mg/kg, s.c.), fentanyl (0.018 mg/kg, s.c.), meperidine (2.6 mg/kg, s.c.), and pentazocine (2.0 mg/kg, s.c.). The electroconvulsive threshold was significantly elevated at doses slightly greater than (fentanyl and meperidine) or about twice the antinociceptive ED50 (morphine and pentazocine). Naloxone antagonized this effect in the case of morphine and fentanyl, but not in the case of meperidine and pentazocine. The threshold for clonic convulsions induced by intravenous infusion of pentetrazole was not influenced by morphine, fentanyl and meperidine, in the dose range studied, but was slightly increased by the smaller doses (2 and 4 mg/kg) of pentazocine. The tonic phase of pentetrazole-induced convulsions was suppressed by the larger doses of fentanyl, meperidine and pentazocine, though smaller doses of pentazocine significantly reduced the threshold for the extensor phase. PMID- 2874518 TI - Serotonergic regulation of the release of renin is not mediated by the autonomic nervous system but involves beta adrenoceptors. AB - p-Chloroamphetamine (PCA) which releases serotonin is known to increase the activity of plasma renin in conscious rats by stimulating serotonergic neurotransmission in the brain. The present studies were designed to investigate whether this effect is mediated from the serotonin receptors in the brain to the kidneys via the sympathetic nervous system. The effect of PCA on the activity of plasma renin was completely blocked by the beta receptor blockers sotalol and atenolol, but was not prevented by the sympathetic inhibitor, bretylium tosylate. In additional studies, chemical sympathectomy with 6-hydroxydopamine, combined with adrenal medullectomy did not prevent the effect of PCA on the activity of plasma renin even though the renal content of norepinephrine was reduced to undetectable levels. Furthermore, complete transection of the spinal cord between the first and second thoracic vertebrae did not prevent the effect of PCA on the activity of plasma renin, suggesting that the sympathetic nervous system and adrenal catecholamines do not mediate the effect of PCA. Studies by others have suggested that extrarenal beta receptors play an important role in the regulation of secretion of renin. The results of the present study support this possibility. The role of the parasympathetic nervous system in the rise in the activity of plasma renin induced by PCA was investigated by pretreatment of the rats with the peripheral muscarinic receptor blocker, methyl atropine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2874519 TI - Noradrenaline modulates the release of [14C]glutamate from dentate but not from CA1/CA3 slices of rat hippocampus. AB - The modulation of the release of [14C]glutamate by noradrenaline (NA) was investigated in slices prepared from the dentate gyrus and from the CA1/CA3 area of the hippocampus. In dentate, but not in CA1/CA3 slices, NA significantly enhanced K+-induced Ca2+-dependent release, and this effect was mimicked by clonidine and isoprenaline, but not by phenylephrine. The enhancement of release by NA was antagonised by propranolol, but not by yohimbine or phentolamine. These results suggest that NA does not modulate the release of glutamate in CA1/CA3, but does so in the dentate gyrus, probably by acting on presynaptically-located beta receptors. PMID- 2874520 TI - An in vivo pharmacological method for the quantitative evaluation of the central effects of alpha 1 adrenoceptor agonists and antagonists. AB - A new in vivo pharmacological method for the quantitative evaluation of alpha 1 adrenoceptor agonists and antagonists has been developed. It consists of recording the myoclonic twitch activity (MTA) of the suprahyoideal muscle of rats anesthetized with urethane. In these animals, the isomers of amphetamine elicited myoclonic twitch activity; their effects were dose-related and the d-isomer was approximately 3.5 times more effective than the l-isomer. While pimozide did not block this response, the postsynaptic alpha 1-antagonist prazosin fully blocked the myoclonic twitch activity induced by d-amphetamine. Other postsynaptic alpha 1-antagonists, such as haloperidol, phenoxybenzamine and clozapine, were also effective in blocking this response to d-amphetamine. Since d-amphetamine elicited myoclonic twitch activity in rats pretreated with reserpine and alpha methyl-p-tyrosine, it was concluded that d-amphetamine exerted a direct alpha 1 adrenoceptor stimulation. In rats pretreated with nialamide and pimozide, l-DOPA elicited myoclonic twitch activity which was dose-related. This effect of l-DOPA was promptly and fully blocked by prazosin. It was concluded that this response to l-DOPA resulted from stimulation of alpha 1-adrenoceptors. The relative potencies of four alpha 1-adrenoceptor stimulants, namely, cirazoline, St-587, ( )SKF 89748A and Sgd 101/75 were determined using this method. The results correlated very well with their relative potencies to increase the diastolic blood pressure of pithed rats. Evidence that myoclonic twitch activity is a centrally-mediated response has also been presented. It appears that the method is a simple, sensitive, versatile and easily quantifiable procedure for the evaluation of the central effects of alpha 1-adrenoceptor agonists and antagonists. PMID- 2874521 TI - Neuropharmacologic analysis of dopaminergic, cholinergic, and GABAergic brain systems in organizing the reflex to time. PMID- 2874522 TI - Location of neurones with cardiovascular and respiratory function, at the ventral surface of the cat's medulla. AB - A study has been made of the ventral surface of the medulla, to identify neurones with cardiovascular and respiratory functions. Experiments were performed on chloralose-anaesthetized, artificially ventilated cats. Ventral medullary neurones were stimulated by microinjections of excitant amino acid (which selectively activates cell bodies), and responses measured in blood pressure, heart rate, renal sympathetic and phrenic nerve activity. A small region of ventral medulla was found, corresponding to the "glycine-sensitive area", from which large increases in blood pressure and renal nerve activity were evoked by amino acid injections. More caudally, another cell group was localized lateral to the hypoglossal nerve roots, and these neurones depressed blood pressure and renal nerve activity. Two distinct regions were found to increase phrenic nerve activity: rostral to the pressor neurones, encroaching on the trapezoid body (roughly corresponding to area "M"), and a caudal group, close to the depressor neurones (i.e. lateral to the hypoglossal roots). No respiratory response could be evoked from medial to the hypoglossal roots (area "L") and stimulation of neurones in area "S" generally depressed phrenic activity. Neurones with cardiovascular and respiratory actions could be distinguished anatomically. Their locations have been mapped and compared with previous studies. PMID- 2874523 TI - Action and specificity of ventral medullary vasopressor neurones in the cat. AB - An investigation has been made into the mode and specificity of action of ventral medullary pressor neurones. These were activated by microinjections of excitant amino acid into the ventral brain surface of chloralose-anaesthetized, artificially ventilated cats, and a number of autonomic responses were measured. Indirect assessment of cardiac output (by CO2 delivery to the lungs) suggested that it was either unchanged or fell during pressor responses. The inference that activating the pressor neurones caused vasoconstriction was confirmed directly for hindlimb and mesenteric vascular beds, by a rise in inflow pressure when they were perfused at constant flow. Sympathetic activity also increased in cervical, splanchnic and inferior cardiac nerves. Bradycardia often (but not always) accompanied pressor responses, but this was abolished by vagotomy, although not by cutting the sinus and aortic nerves. In vagotomized cats, tachycardia could be produced during pressor responses even after either bilateral adrenalectomy or removal of the stellate ganglia, indicating both direct sympathetic drive to the heart and release of adrenal catecholamines. Plasma adrenaline levels were measured and found to increase by up to 20.2 times control values, plasma noradrenaline up to 12.6 times, and dopamine by a smaller amount. Activating ventral medullary pressor neurones appeared to have no significant action on pupils, nictitating membranes or piloerection. In three adrenalectomized, vagotomized cats, only small, inconsistent effects were measured on intestinal motility following pressor neurone excitation. However, large electrodermal responses could be evoked from the ventral medulla, but from a distinct area medial to the pressor neurones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2874524 TI - Chemoresponsiveness of intracellular nuclei neurones to L-aspartate, L-glutamate and related derivatives in rat cerebellar slices maintained in vitro. AB - The sensitivity of intracerebellar nuclei neurones to pulse applications of L aspartate, L-glutamate, N-methyl-D,L-aspartate and quisqualate was tested in rat cerebellar slices maintained in vitro. The responses of the nuclear neurones to the four agonists consisted of a transient and dose-dependent increase in their firing of simple spikes. When suprathreshold currents were used, quisqualate induced the highest increase in the spike discharge frequency of the cells. Quisqualate mediated responses were unaffected by steady applications of 2-amino 5-phosphonovalerate, whereas the sensitivity of the responses induced by the three other agonists was in the order N-methyl-D,L-aspartate, L-aspartate, L glutamate. When the superfusing solution was devoid of Mg2+ ions, N-methyl-D,L aspartate and L-aspartate mediated responses were much potentiated, while quisqualate induced responses were not enhanced. In such a medium, L-glutamate elicited responses were more or less potentiated depending on cells. These results suggest that rat intracerebellar nuclei neurones bear both N-methyl-D aspartate and non-N-methyl-D-aspartate, probably quisqualate, receptors, and that L-aspartate and L-glutamate have a mixed action upon both types. L-Aspartate preferentially activates N-methyl-D-aspartate receptors, whereas L-glutamate predominantly acts via non-N-methyl-D-aspartate receptors. Furthermore, the potency of L-glutamate in activating N-methyl-D-aspartate receptors appears to vary as a function of the cells. PMID- 2874525 TI - Distribution of somatostatin receptors in the human brain: an autoradiographic study. AB - High affinity somatostatin receptors have been measured in postmortem brains from 18 neurologically asymptomatic patients (mean age: 67 years) using the stable somatostatin analog 125I-204-090, DPhe-Cys-Tyr-DTrp-Lys-Thr-Cys-Thr(ol), as radioligand. In homogenates from human frontal cortex, high affinity (Kd = 0.52 nM; Bmax = 557 fmol/mg protein) receptors with pharmacological specificity for somatostatin, [D-Trp8]somatostatin and somatostatin-28 were found. The CNS distribution of these receptors was studied by autoradiography. Somatostatin receptors were distributed in varying densities throughout the whole brain. High concentrations are found in all cortical layers, the deeper layers (V-VI) being usually more dense than the superficial layers (I-III). The limbic system is heavily labeled, in particular hippocampus (CA1, dentate gyrus), most of the nuclei of the amygdala, and the habenula. Also parts of the basal ganglia are very rich in somatostatin receptors: the nucleus caudatus as well as the nucleus accumbens are very dense, whereas the globus pallidus is virtually unlabeled. Interestingly, significant amounts of somatostatin receptors are found in the human cerebellum, which is devoid of endogenous somatostatin. Other discrete areas of the CNS are enriched with somatostatin receptors: locus coeruleus, tuberal nuclei of the hypothalamus, claustum, tuberculum olfactorium as well as spinal trigeminal nucleus and substantia gelatinosa of the spinal cord. The substantia innominata is poor in somatostatin receptors. In general there is a good correlation in the distribution of somatostatin receptors in the human and rat brain and there is a reasonable correlation with endogenous somatostatin levels in human brain tissue, particularly in the larger structures. The very high density and the specific localization of somatostatin receptors in strategic key points in the CNS such as cortex, basal ganglia, limbic system and substantia gelatinosa suggests an important role of somatostatin in cognitive, sensory and extrapyramidal motor functions. The significance of somatostatin receptors in the human cerebellum remains to be elucidated. PMID- 2874526 TI - Gonadotropin-releasing hormone immunoreactive neurons with access to fenestrated capillaries in mouse brain. AB - Gonadotropin-releasing hormone (GnRH) producing neurons which have access to fenestrated capillaries were identified through a combination of indirect immunofluorescence for GnRH with a fluorescein-taged second antibody and histochemical demonstration of the localization of blood borne and retrogradely transported horseradish peroxidase. In the mouse, GnRH positive neurons were present in the septum, which includes neurons originating from the nervus terminalis, the nucleus medialis and triangularis septi, and the nucleus of the diagonal band. Also, GnRH immunoreactive neurons could be seen in the lateral anterior hypothalamus, the nucleus preopticus medianus, the rostral nucleus periventricularis hypothalami and, to a lesser extent, the nucleus preopticus medialis. Single GnRH positive neurons were found in the nucleus supraopticus, the bed nucleus of the stria terminalis and the cingulate cortex. GnRH neurons which showed uptake of horseradish peroxidase were located in all of these regions and intermingled with unlabeled GnRH neurons. No preferential topographical concentration of GnRH neurons with access to the fenestrated vasculature was apparent. In animals in which GnRH secretion was stimulated by castration for 2 weeks, 65% of all GnRH neuronal perikarya contained horseradish peroxidase. This was reduced to 35% after a 2-week treatment of ovariectomized animals with 10 micrograms/day estradiol while the total number of immunoreactive GnRH cells remained unchanged. No differences in the number of GnRH-horseradish peroxidase positive cells was seen when the dose of horseradish peroxidase of the survival time were increased. While the presence of certain GnRH neurons with dual actions via collaterals cannot be excluded, the results suggest that there are two populations of GnRH neurons, one with access to fenestrated capillaries which is probably related to neurosecretory endocrine regulation of anterior pituitary gonadotropin secretion, and one without access to fenestrated capillaries which is probably related to intracerebral neurotransmission only. PMID- 2874527 TI - Huntington's disease: effect of cysteamine, a somatostatin-depleting agent. AB - Somatostatin levels in the basal ganglia are elevated in Huntington's disease. A controlled therapeutic trial of the somatostatin-depleting agent, cysteamine, was therefore conducted in five patients, including one with the rigid-akinetic form. Maximum tolerated dosage for 2 weeks produced no consistent change in extrapyramidal or dementia scores. Somatostatin concentrations were not significantly altered in plasma or CSF. Growth hormone levels, on the other hand, more than doubled, suggesting a functionally significant decrease in central somatostatin levels. PMID- 2874528 TI - [Description of 3 cases of acute necrotico-hemorrhagic pancreatitis with different etiologies: treatment with somatostatin]. PMID- 2874529 TI - [Beta-blockers in gastroenterology]. PMID- 2874530 TI - [Up-date on urticaria]. PMID- 2874531 TI - [Changes in portal hemodynamics during pharmacologic stimulation: somatostatin vs glypressin]. AB - Sixteen patients with cirrhosis of the liver and a history of haemorrhaging oesophageal varices all given Warren-type splenorenal bypasses were subjected to intraoperative measurement of portal flow and pressure after the administration of Somatostatin and Glypressin. Glypressin was distinctly more effective in producing a significant and long term reduction in portal flow and pressure. Somatostatin made no significant difference to these parameters. PMID- 2874532 TI - In vitro effects of endogenous opiate peptides on thyrotropin function: inhibition of thyrotropin-releasing hormone release and absence of effect on thyrotropin release. AB - Thyrotropin-releasing hormone (TRH) or thyroid-stimulating hormone (TSH) was measured by radioimmunoassay in the incubation medium of rat hypothalami or anterior pituitary halves, respectively. We studied the effect of opioid peptide addition (10(-8) to 10(-6) M) on TRH or TSH release. alpha- or beta-Endorphin decreased TRH release in a dose-dependent manner while only 10(-6) M Leu- or Met enkephalin decreased TRH release. These inhibitory effects were prevented by addition of naloxone (10(-5) M). In the dose range used none of the opioid peptides modified TSH release. These results indicate that opioid peptides may play a role in the regulation of thyrotropin secretion via a hypothalamic action on TRH release. PMID- 2874533 TI - Testosterone inhibition of tyrosine hydroxylase expression in the hypothalamic arcuate nucleus. AB - Immunohistochemistry was used to detect tyrosine hydroxylase (TH)-containing neurons in the hypothalamic arcuate nucleus in male rats. Two weeks following castration, the number of TH-positive cells was significantly greater than in intact controls. The castration-responsive TH-positive cells were uniformly distributed throughout the mediolateral extent of the arcuate nucleus. Treatment with testosterone significantly suppressed the castration response, whereas neither estradiol nor 5 alpha-dihydrotestosterone were effective. The number of TH-positive arcuate neurons in the female was similar to that in the male. Ovariectomy did not affect the number of TH-positive neurons. These findings indicate that TH expression is tonically inhibited in the tuberoinfundibular dopaminergic system of the male rat by testosterone. PMID- 2874534 TI - Somatostatin and calcitonin gene-related peptide synergistically modulate spinal sensory and reflex mechanisms in the rat: behavioral and electrophysiological studies. AB - Using behavioral and electrophysiological techniques evidence was obtained that somatostatin (SOM) and calcitonin gene-related peptide (CGRP) synergistically increase spinal cord excitability. In the behavioral experiments 1 microgram SOM or 1 microgram SOM + 20 ng CGRP injected intrathecally (i.t.) elicited a biting/scratching response lasting about 20 min. One microgram SOM combined with 200 ng, 2 micrograms or 20 micrograms CGRP caused an increase in the duration of this response. CGRP by itself (20 micrograms i.t.) had no effect. In the physiological experiments 10 ng SOM or 100 ng CGRP i.t. caused a brief facilitation of the hamstring flexion reflex (1-5 min) whereas 10 ng SOM + 100 ng CGRP synergistically facilitated the reflex for 40-75 min. The results are qualitatively similar to those obtained with substance P + CGRP and further strengthen the role of SOM in sensory transmission involving C-afferents. PMID- 2874535 TI - Is tofisopam an atypical anxiolytic? AB - This review describes the behavioural and biochemical profile of tofisopam, a 3,4 benzodiazepine that differs considerably in its effects and mechanisms of action from classical 1,4-benzodiazepines. In man tofisopam appears to possess anxiolytic activity without appreciable sedative and muscle relaxant side effects; in animals, however, tofisopam totally lacks anxiolytic and anticonvulsant properties in tests sensitive to the effects of 1,4 benzodiazepines. Tofisopam also has mixed dopamine agonist and antagonist-like properties in several in vivo and in vitro tests in animals. The possible relevance of the latter effects to the unusual behavioural profile of tofisopam are discussed, and its effects compared with those of buspirone, a novel anxiolytic that has similar activity at benzodiazepine and dopamine systems. It is proposed that these two drugs may represent a novel class of compounds that reduce anxiety by increasing the ability of patients to cope with daily tasks, rather than classical anxiolytics, that reduce anxiety by tranquilization. PMID- 2874536 TI - Neurochemical coupled actions of transmitters in the microvasculature of the brain. AB - The discovery that monoamine nerves end on the central microvessels of the choroid plexus, pia-arachnoid and parenchyma has prompted an intense investigation as to their physiological and neuropathological roles. The source of the monoamine fibers to the pial vessels and choroid plexus was shown to be the superior cervical ganglion. Ganglionic stimulation causes vasoconstriction or vasodilation of pial vessels, an event depending upon the functional ratio of alpha to beta adrenergic receptors. Moreover, stimulation of the superior cervical ganglion evokes an inhibition of cerebrospinal fluid formation in choroid plexus. The locus coeruleus is the site of adrenergic nerve supply to the parenchymal capillaries and stimulation of this nucleus increases capillary permeability to small molecules and water. Neurotransmitter receptors (adrenergic, histamine, adenosine, dopamine, prostacyclin, prostaglandins and specific amino acids or neuropeptides) have been identified on microvessels and in many instances these transmitter actions are coupled to cyclic AMP synthesis. Moreover, cyclic AMP has been shown to increase the rate of capillary endothelial pinocytosis and produce brain edema. In small vessels containing smooth muscle cells cyclic AMP production improves cerebral blood flow via an initiation of vasodilatory processes. The presence of receptors for serotonin and acetylcholine have likewise been demonstrated to occur on cerebral microvessels. Limited information is available as to the receptor coupled actions of these two transmitters, but cholinergic mechanisms may act to restrict catecholamine induced formation of cyclic AMP. Altered sensitivity of microvessels to neurotransmitters has been demonstrated following conditions of stroke, hypertension, aging, diabetes and X-irradiation. PMID- 2874537 TI - Alprazolam-induced manic reaction. PMID- 2874538 TI - Metastatic pheochromocytoma in pregnancy and fetal biophysical assessment after maternal administration of alpha-adrenergic, beta-adrenergic, and dopamine antagonists. AB - Metastatic pheochromocytoma, a rare complication of pregnancy, was managed from 30 weeks' gestation until delivery three weeks later with a combination of alpha adrenergic blockade (Minipres) beta-adrenergic blockade (Timolol), and dopamine synthesis inhibition (Demser). The biophysical parameters of fetal heart rate (FHR) baseline, variability, and reactivity, as well as fetal breathing movements, body movements, tone, and amniotic fluid volume were followed sequentially during this period. A 1450-g growth-retarded infant, who subsequently did well, was delivered by cesarean section; the mother received combined surgical and medical therapy for her metastatic disease in the postpartum period. The initial fetal biophysical alteration observed was a reduction in mean FHR baseline rate; further biophysical test abnormalities appeared only after overt fetal compromise was evident. Sequential multiple parameter biophysical testing in such circumstances appears to be a valid and valuable approach to antepartum management. PMID- 2874539 TI - [Fractures of the child's foot]. AB - The incidence of fractures of the foot in childhood depends considerably upon whether the site of fracture is the hindfoot, midfoot or forefoot. Fractures of the talus or calcaneus are rare. However, in the literature there are a significant number of publications on these fractures from the point of view of arthrosis problems or aseptic necrosis. In contrast, only few reports have been published about mid- or forefoot fractures in children. Generally, treatment problems and long-term prognosis are believed to be unproblematic. However, follow-up studies of these fractures have shown that some of them can be followed by significant disabilities concerning the plantar arch or the gait pattern. More extensive follow-up studies seem to be necessary to point out specific recommendations for treatment of foot fractures in childhood. Some of the problems are discussed in detail. PMID- 2874540 TI - [Foot dislocation in the child]. AB - Fibulotalar distortions of the ankle are differentiated from distortions with and without instability, as well as instabilities with and without decompensation. Physiological lateral tilting of the talus is shown to be dependent on age and sex as well as on the kind of ligament lesion--avulsion or rupture--likewise dependent on age. The factors involved in the early or late prognosis are discussed. A prospective study is introduced, which differentiated is between primary and secondary distortions or more. Primary distortions (without an osseal lesion) are treated conservatively. Secondary additional distortions with no case history of compensation for the instability are treated operatively, as are avulsions with displaced osseal fragments. PMID- 2874541 TI - [The sports shoe]. AB - Today children wear sport shoes more and more on a daily basis, although the sport shoe was originally designed to serve just for sports purposes. Good sport shoes for children must therefore fulfill the criteria for everyday shoes as well as the requirements for good running shoes, namely, adequate cushioning in the heel area, support during pronation and directing the rolling movement for push off using the forefoot. For these purposes, the shoe should not represent a miniaturized version of an adult sport shoe, but must be designed for the form of the child's foot and also take the fragility of the connective tissue into consideration, in addition to user comfort, fit, and foot ventilation. In comparison with today's models, therefore, good sports shoes could be improved in many areas. PMID- 2874542 TI - Transient neonatal 'athyreosis' resulting from thyrotropin-binding inhibitory immunoglobulins. AB - Recognition of transient forms of neonatal hypothyroidism is difficult because of the urgency of thyroxine treatment. In the present report the first child born to a mother with Graves' disease developed transient hyperthyroidism during the newborn period. The mother underwent radioactive iodine treatment and was maintained euthyroid on l-thyroxine. Two subsequent children were detected by newborn thyroid screen to have low thyroxine and markedly elevated serum thyrotropin (TSH) levels. Technetium 99 metastable and iodine 123 scans at 22 days of age showed the second child to be athyreotic. The third child was not scanned. All three children were nongoitrous at birth. Patients 2 and 3 had continuous TSH suppression with thyroxine therapy for 3 and 4 years. Thyroid function measurements after discontinuation of therapy for 8 weeks were normal, and both children had normal 123I thyroid scans. The mother was found to have potent TSH-binding inhibitory immunoglobulin (TBII) levels in her serum (85.5%). A fourth child with low thyroxine and elevated TSH was born to a mother on a regimen of l-thyroxine for hypothyroidism. 99mTc scan at 26 days of age showed no thyroid tissue and was normal at 3 months. TBII activity was 35% in the maternal serum and absent in the infant's serum. The above laboratory and clinical data are compatible with the blocking nature of TBII, resulting in transient newborn hypothyroidism and an athyreotic appearance on scan. The TBII measurement can be a useful predictor of neonatal hypothyroidism as well as confirm the transient nature of the disease in newborns. PMID- 2874543 TI - [Nocturnal asthma and its treatment]. PMID- 2874544 TI - [Bronchial hyperreactivity. II. Diagnostic methods]. AB - Bronchial hyperreactivity is studied for the evaluation of airways' response to stimuli that provoke bronchoconstriction in hyperreactive subjects. Exercise is often used, especially in children. This method in simple, sufficiently tolerated and reproducible. The inhalation of ultrasonically-nebulized distilled water is a simple, reproducible and rapid to perform in the majority of adult patients test; in childhood it is poorly inquired. Pharmacological tests (with histamine or methacholine) have a greater sensitivity and reproducibility. Aspecific bronchoprovocation with methacholine is a diagnostic method that allows the diagnosis of bronchial hyperreactivity in asymptomatic subjects with asthma, recurrent cough and recurrent bronchopneumonia. PMID- 2874545 TI - [Current possibilities of the surgical correction of intersexual states]. AB - The diagnosis of genital anomalies must be approached with the utmost care, for the results will decide the future sexual life of the patient. Before corrective surgery is performed, it is absolutely necessary to complete all endocrinologic and genetic studies. It is possible to predict with a high degree of confidence the hormonal and sexual development of intersexual children during puberty and thus to choose the "right" operation for a given patient. So occasionally situations will arise in which the sex that is selected for a child differs from its gonadal or chromosomal sex. In author's experience almost all genital anomalies can be surgically corrected with a very good cosmetic result. It is recognised that in a great number of cases surgery alone cannot be sufficient treatment, endocrinological and psychological management are equally important. It is current opinion that early corrective surgery must be advised. PMID- 2874546 TI - [Aarskog syndrome. Description of a case with significant anomalies of the gonads]. AB - The Aarskog syndrome is characterized by short stature, hypertelorism, cryptorchidism, typical scrotal fold, clinodactyly and brachydactyly. From the available data the prognosis about definitive stature and fertility is good. In our case the anomalies of the testis are severe and we think that infertility is probable. PMID- 2874547 TI - Corticosteroidogenesis modulation by beta-endorphin and dynorphin1-17 in isolated rat adrenocortical cells. AB - Two opioid peptides, beta-endorphin and dynorphin1-17 were bioassayed with isolated rat adrenocortical cells. beta-Endorphin increases basal production of corticosterone as well as the adrenal responsiveness to low doses of ACTH, these effects being partially reversed by naloxone. Dynorphin1-17, without affecting basal corticosterone synthesis, increases adrenocortical responsiveness to ACTH; naloxone does not influence this effect. It is suggested that peripheral opioid peptides may participate in the maintenance of the homeostatic balance by modulating adrenal corticosteroidogenesis. PMID- 2874548 TI - Reversed-phase HPLC study on the in vitro enzymic degradation of dermorphin. AB - A high-performance liquid chromatographic (HPLC) method for the separation of the opioid heptapeptide dermorphin and related fragments has been developed. The chromatographic system was applied in the study of the kinetics of degradation of dermorphin (Der) in various tissues. Der was found to be extremely resistant to human and rat plasma (T 1/2 greater than 180 min). Upon incubation with homogenates of rat brains and kidneys, Der was cleaved with a half-life of 20.8 +/- 2.2 min and 2.4 +/- 0.3 min respectively. The catabolite formed was identified, in both tissues, as the N-terminal tetrapeptide H-Tyr-D-Ala-Phe-Gly OH. The stability to rat kidney and brain of the N-terminal hexa- and pentapeptides and of the [4 psi 5, NHCO] Der analogue was also investigated. The nature of the enzyme systems involved in the in vitro degradations is discussed. PMID- 2874550 TI - [Risks of beta-blockers and calcium inhibitors in amyloid cardiopathy]. PMID- 2874549 TI - Co-expression of vasopressin with beta-endorphin and dynorphin in individual cells from the ovaries of Brattleboro and Long-Evans rats: immunocytochemical studies. AB - The distribution of arginine-vasopressin (AVP)-, oxytocin-, beta-endorphin (beta EP)- and dynorphin-immunoreactive cells was examined by peroxidase-antiperoxidase (PAP) immunocytochemistry in the ovaries of Brattleboro and Long-Evans (LE) rats. The ovarian distribution of the peptide-immunoreactivity is indistinguishable between the two strains. AVP- and beta-EP-immunoreactivity is co-localized in the majority of luteal cells, and in some cells scattered in the interstitial tissue. Of the AVP/beta-EP-positive cells, 1-2% also contained immunoreactive (ir) dynorphin. Some cells in the interstitium contained only ir-AVP (approximately 50%) or only ir-dynorphin (approximately 5%); in the corpora lutea, however, no luteal cells appeared to contain only one peptide. AVP-immunoreactivity is also present in theca cells surrounding secondary and large, antral follicles; ir oxytocin was not observed in any ovarian cell type in the rat. These data suggest that most luteal, and some interstitial, cells in the ovary have the capacity to produce and store up to three different neuropeptides. PMID- 2874551 TI - [Takayasu's disease. Value of digital intravenous angiography. 44 cases]. AB - Forty-four patients with Takayasu's arteritis were explored by digital intravenous angiography either for diagnostic purposes and pre-therapeutic assessment (n = 29) or immediately after surgery (n = 15). There were 36 women, 6 men and 2 children; mean age was 31 years. The contrast medium (mean volume 140 ml) was injected into central (74%) or peripheral (26%) veins. No other angiographic exploration was contemplated in 24 patients selected for medical treatment. Among 15 patients destined to surgery or percutaneous angioplasty, 13 were operated upon without further angiography and 2 underwent arteriography since the distal vascular bed beyond the major lesions could not be evaluated adequately. Data obtained from post-operative evaluation (n = 15) were satisfactory, with 1 failure in this group. Digital intravenous angiography seems to be reliable enough to be used as first examination in patients with suspected Takayasu's arteritis. The procedure is well tolerated and can be repeated for optimum determination of the operation date. Arteriography can now be reserved to those rare cases where digital angiography has failed; it can then be limited to the study of a specific territory, the site of puncture being located by digital angiography. PMID- 2874552 TI - [Dynamics of various indicators of cellular immunity in patients with diffuse toxic goiter after drug therapy]. AB - The purpose of the investigation was to study some indices of the immune system of patients with diffuse toxic goiter (DTG) before multimodality thyrostatic therapy and after achieving clinical remission. A total of 30 DTG patients with an average severity of disease were examined. The immune status was evaluated according to the content of T-lymphocytes, T-suppressors, Fc gamma-lymphocytes and antigen-binding lymphocytes (ABL) responsive to thyroglobulin. Conservative therapy included mercazolyl, beta-adrenergic blockers, sedative and cardiac drugs. A drop of T1T gamma and Fc gamma-lymphocytes was revealed in the period of the manifestation of the clinical signs of disease. The indices of ABL responsive to thyroglobulin significantly exceeded the relative and absolute indices of the control group. Multimodality drug therapy resulted in the deepening of T lymphocyte deficiency, a significant rise of T gamma 1 and T gamma 2 as compared to the initial levels. A tendency to a decrease in the level of Fc gamma lumphocytes was noted after the therapy. The relative and absolute values of the ABL indices significantly decreased, however a significant increase in these indices compared to the control ones maintained. PMID- 2874553 TI - Complete nucleotide and deduced amino acid sequence of bovine phenylethanolamine N-methyltransferase: partial amino acid homology with rat tyrosine hydroxylase. AB - We report here the isolation of a cDNA clone containing the full coding region of bovine phenylethanolamine N-methyltransferase (PNMTase, EC 2.1.1.28, S-adenosyl-L methionine:phenylethanolamine N-methyltransferase). The complete nucleotide sequence of the cDNA has been determined, and the amino acid sequence of PNMTase deduced. Cultured cells transfected with an expression vector containing this cDNA produced high levels of PNMTase enzymatic activity. Antibodies specific for tyrosine hydroxylase [EC 1.14.16.2, tyrosine 3-monooxygenase; L-tyrosine, tetrahydrobiopterine: oxygen oxidoreductase (3-hydroxylating)], the first enzyme in the catecholamine pathway, possess a striking affinity for the PNMTase protein synthesized in vitro. Comparison of the deduced amino acid sequence of bovine PNMTase to rat tyrosine hydroxylase reveals that PNMTase shares significant homology with tyrosine hydroxylase and supports previous protein and immunological data suggesting that the catecholamine biosynthetic enzymes are structurally related. PMID- 2874554 TI - GH3 pituitary adenoma cells can reverse thymic aging in rats. AB - Thymic size and T-cell function decrease with age, and it has not yet been possible to totally reverse this thymic atrophy and completely restore T-cell dependent immune functions. In this study, GH3 pituitary adenoma cells, which secrete growth hormone and prolactin, were implanted subcutaneously into 16- and 22-month-old female Wistar-Furth rats and the rats were sacrificed approximately 2 months later. Only thymic remnants were detected in aged, non-implanted rats, but thymus glands were found in both the 18- and the 24-month-old rats that had been implanted with GH3 cells. Thymus glands from the GH3-implanted 18-month-old rats contained distinct cortical thymocytes and medullary epithelial cells. Depending on the concentration of phytohemagglutinin or concanavalin A, T-cell proliferative responses of splenocytes from these implanted rats were 2- to 5 fold greater than those of 18-month-old controls. At the optimal concentration of mitogen, proliferative responses to either lectin could be restored to those levels observed in splenocytes from 3-month-old Wistar-Furth females. Thymus glands from 24-month-old GH3-implanted rats contained more cortical thymocytes and fewer fat vacuoles than controls, but they were not totally reconstituted. No significant lectin-induced T-cell proliferative responses or IL-2 secretion were detected in 24-month-old control rats, but splenocytes from GH3-implanted rats showed augmented T-cell proliferative responses and increased synthesis of IL-2. Fluorescence-activated cell-sorter analysis of thymocytes revealed that 24-month old rats implanted with GH3 cells had a higher proportion of lymphocytes with the Thy-1.1 and helper-T-cell phenotypes. These data show that it is possible to regenerate normal thymic tissue in situ and reverse the natural loss in cell mediated immunity that occurs with aging. PMID- 2874555 TI - Lithium dampens neurotransmitter response in smooth muscle: relevance to action in affective illness. AB - Lithium, by inhibiting inositol phosphate metabolism, interferes with the phosphatidylinositol ("phosphoinositide") cycle, which is stimulated by numerous hormones and neurotransmitters. To examine the relevance of this action to neurotransmission, we evaluated effects of lithium treatment on smooth muscle responses to transmitters. In lithium-pretreated tracheal muscle, the relaxation following carbachol or histamine contractions is retarded. Lithium does not affect relaxation following contractions elicited by treatment with KCl and phorbol 12,13-diacetate in combination, which bypasses receptor stimulation of the phosphatidylinositol cycle. Half-maximal effects of lithium occur at 1 mM, corresponding to therapeutic concentrations. Dampening of neurotransmitter responses by lithium treatment may explain the unique ability of lithium to relieve and prevent both mania and depression. PMID- 2874556 TI - Membrane lipid phase as catalyst for peptide-receptor interactions. AB - Catalysis of ligand-receptor interactions is proposed as an important function of the lipid phase of the cell membrane. The catalytic mechanism is deduced from observed specific interactions of amphiphilic peptides with artificial lipid bilayers. In our model a direct ligand-receptor reaction is replaced by multiple sequential steps including surface accumulation of charged ligands, ligand membrane interactions, and ultimately binding to the receptor itself. By dividing the total free energy of binding among several steps, the energy per step, including the intrinsic receptor interaction energy, is kept to moderate values. The model thereby yields simple explanations for the large apparent association constants, the high association and dissociation rates, and the heterogeneity of binding sites so frequently found with pharmacological and biochemical ligand receptor interactions. Furthermore, the measured apparent association constant is a function of the whole system rather than just the receptor. The same, fully functional receptor may show different binding characteristics in different surroundings, such as in another tissue or in a reconstituted system. PMID- 2874557 TI - Covalent modification of the glnG product, NRI, by the glnL product, NRII, regulates the transcription of the glnALG operon in Escherichia coli. AB - Transcription from nitrogen-regulated promoters, such as glnAp2, requires the glnG gene product, NRI, as well as the rpoN(glnF) gene product, sigma60, and is regulated by the glnL gene product, NRII. We find that in a reaction mixture containing NRI, NRII, and ATP, NRII catalyzes the transfer of the gamma phosphate of ATP to NRI. This covalent modification of NRI occurs concurrently with the acquisition of the ability by the reaction mixture to activate transcription from glnAp2. In the presence of PII, the product of glnB, NRII catalyzes the removal of the phosphate from NRI-phosphate. This reaction occurs concurrently with the loss by the reaction mixture of the ability to activate transcription from glnAp2. On the basis of this evidence, we propose that NRI-phosphate activates transcription from nitrogen-regulated promoters and that the role of NRII is control of the formation and breakdown of NRI-phosphate in response to cellular signals of nitrogen availability. PMID- 2874558 TI - In situ hybridization to localize mRNA encoding the neurotransmitter synthetic enzyme glutamate decarboxylase in mouse cerebellum. AB - Glutamate decarboxylase (GAD; EC 4.1.1.15) is responsible for the synthesis of the neurotransmitter gamma-aminobutyric acid (GABA). We have used a cDNA sequence encoding GAD to produce a single-stranded RNA hybridization probe for GAD mRNA. This probe detects GAD mRNA in individual cells in sections of mouse cerebellum. The specificity of in situ hybridization with this probe rests on four criteria: the distribution of labeled cells matched the results we and others obtain with GAD immunohistochemistry (Purkinje, Golgi II, stellate, and basket neurons were labeled, whereas granule cells and glia were not); a negative control probe having a sequence identical to GAD mRNA did not specifically label any cerebellar cells; prior treatment of the sections with RNase abolished specific labeling; the labeling showed the melting behavior typical of nucleic acid hybrids. Translation of GAD mRNA is apparently restricted to neuronal cell bodies since GAD mRNA was detectable in neuronal perikarya but not in terminals. Also, the choice of GABA as a neurotransmitter appears to be made at the level of transcription since granule neurons did not contain detectable GAD mRNA. The level of GAD mRNA varied among the classes of neurons as well as from cell to cell within each neuron type. PMID- 2874559 TI - Hyperpolarization of the membrane potential caused by somatostatin in dissociated human pituitary adenoma cells that secrete growth hormone. AB - Membrane electrical properties and the response to somatostatin were examined in dissociated human pituitary adenoma cells that secrete growth hormone (GH). Under current clamp condition with a patch electrode, the resting potential was -52.4 +/- 8.0 mV, and spontaneous action potentials were observed in 58% of the cells. Under voltage clamp condition an outward K+ current, a tetrodotoxin-sensitive Na+ current, and a Ca2+ current were observed. Cobalt ions suppressed the Ca2+ current. The threshold of Ca2+ current activation was about -60 mV. Somatostatin elicited a membrane hyperpolarization associated with increased membrane permeability in these cells. The reversal potential of somatostatin-induced hyperpolarization was -78.4 +/- 4.3 mV in 6 mM K+ medium and -97.2 +/- 6.4 mV in 3 mM K+ medium. These reversal potential values and a shift with the external K+ concentration indicated that membrane hyperpolarization was caused by increased permeability to K+. The hyperpolarized membrane potential induced by somatostatin was -63.6 +/- 5.9 mV in the standard medium. This level was subthreshold for Ca2+ and Na+ currents and was sufficient to inhibit spontaneous action potentials. Hormone secretion was significantly suppressed by somatostatin and cobalt ions. Therefore, we suggest that Ca2+ entering the cell through voltage-dependent channels are playing an important role for GH secretion and that somatostatin suppresses GH secretion by blocking Ca2+ currents. Finally, we discuss other possibilities for the inhibitory effect of somatostatin on GH secretion. PMID- 2874560 TI - Tyrosine 3-hydroxylase in rat brain and adrenal medulla: hybridization histochemistry and immunohistochemistry combined with retrograde tracing. AB - Rat brain and adrenal gland were analyzed by hybridization histochemistry using an RNA probe complementary to mRNA for tyrosine 3-hydroxylase (TyrOHase; tyrosine 3-monooxygenase, EC 1.14.16.2), by immunohistochemistry using TyrOHase antiserum, and by retrograde tracing using the fluorescent compound Fast blue. Cell bodies in the ventral mesencephalon contained mRNA for TyrOHase, and these cells were also TyrOHase immunoreactive. After injection of Fast blue into the striatum, such double-labeled cells in addition contained the retrograde tracer, showing that these cells send axonal projections to the injection site. These results show that hybridization histochemistry can be used to identify transmitter specific neuron populations and that their projections can be established. PMID- 2874561 TI - Chronic stimulation modifies the isotonic shortening velocity of denervated rat slow-twitch muscle. AB - Rat soleus muscles were denervated and stimulated in vivo for periods of up to 104 days. Stimuli used were trains of 1 ms pulses at 100 Hz delivered for periods of 1 s; trains were repeated every 10-100 s. In a majority of animals the tension of the muscles was maintained at about 10% of normal, equivalent to muscles denervated but unstimulated for 20 days. At the longest periods the stimulated muscles developed ten times more tension than ones that were denervated but not stimulated. In denervated and denervated-stimulated muscles twitch contraction and relaxation times were prolonged, compared with controls, for up to 3 weeks. Thereafter both sets showed a speeding of the isometric twitch that was greater in the stimulated muscles. At the longest periods the twitch was as short as that of a denervated fast muscle. Stimulation did not affect contralateral denervated muscles. Twitch: tetanus ratios remained high despite stimulation, and muscles showed little post-tetanic potentiation. Tension developed more rapidly in the tetani of the stimulated muscles, even allowing for larger final values. Maximum velocity of shortening was increased in many of the stimulated muscles, and there was a proportional flattening of the force-velocity curve, i.e. a/P0 increased. Maximum velocity and a/P0 increased reciprocally with twitch time to peak, so that those muscles that had twitches most changed by stimulation also had their isotonic properties modified to the greatest extent. Even at the longest period of stimulation, twitch time course and tetanic tension were not converted to those of normal fast muscle. PMID- 2874562 TI - Coupling between transmembrane calcium transport and membrane potential in retinal rod discs. AB - Changes in the transmembrane potential of bovine rod discs were studied by use of the potential-sensitive fluorescence probes diS-C3-(5) and diBA-C4-(5). The disc membrane was shown to be impermeable to potassium ions. Their concentration in the disc is as high as 2.1 +/- 0.3 mM. The permeability of the disc membrane to Ca2+ was shown to be selective. The accumulation and release of Ca2+ were found to be accompanied by the generation of inside positive and inside negative transmembrane potentials, respectively. The uptake of Ca2+ in the discs may operate against the concentration gradient of the ion. The value of the potential developed is directly proportional to the logarithm of free Ca2+ concentration in the medium (delta phi m = 11.2 +/- 1.6 mV at 4.85 microM Ca2+fr). The accumulation of Ca2+ is decreased by sodium ions and totally inhibited by monensin. This indicates that a Na-Ca exchange process participates in Ca2+ uptake of photoreceptor discs. PMID- 2874563 TI - Effects of H2-blocking agents on hepatocytes in vitro: correlation with potential for causing hepatic disease in patients. AB - The adverse effects on an in vitro model of oxmetidine, an H2-blocking agent which has been shown to produce hepatic injury in 1 to 4% of patients, were compared with those of cimetidine and ranitidine which have led to only rare instances of hepatic injury. Suspensions of hepatocytes, freshly isolated from Sprague-Dawley rats, were exposed to the three drugs. Oxmetidine, in concentrations of 3 X 10(-3) M or greater, led to leakage of AST into the medium after 4 hr of incubation. Ranitidine and cimetidine, in concentrations up to 5 X 10(-3) M, produced no identifiable leakage. Pretreatment of rats with phenobarbital, 3-methylcholanthrene, or SKF 525A resulted in no significant enhancement or inhibition of the oxmetidine effects. These results suggest that the adverse effects of oxmetidine on the hepatocytes are produced by the native compound, not a metabolite. The positive correlation between in vivo and in vitro toxicity supports the view that in vitro testing may prove to be of use in predicting the hepatotoxic potential of a drug. PMID- 2874564 TI - Anxiolytic-like action of melatonin on acquisition but not performance of DRL. AB - The behavioural effects of melatonin have been attributed to a general reduction in motor activity; interference with memory fixation; a decrease in emotionality; or an anxiolytic action. The present experiments compared the effects of melatonin with an anxiolytic benzodiazepine, chlordiazepoxide (Librium), on a schedule of differential reinforcement of low rates of response (DRL) increasing 'burst' responding and premature responding. No doses of melatonin tested (0.03 8.1 mg/kg, IP) affected performance of well-learned DRL. Both low (0.03 mg/kg) and high (1.0 mg/kg) doses of melatonin impaired acquisition of DRL in a similar manner to chlordiazepoxide (5.0 mg/kg) and to much the same extent. Chlordiazepoxide had its usual effects on both acquisition and performance of DRL. These results show that melatonin shares a subset of the effects of chlordiazepoxide. The nature of the effects favours an 'anxiolytic' hypothesis of melatonin action rather than the other hypotheses so far proposed. PMID- 2874565 TI - Nicotine-induced convulsions in cats and central nicotinic receptors. AB - The effects were investigated of intracerebroventricular (ICV) injections in the cat of ganglionic blocking agents, antimuscarinic drugs, alpha and beta adrenergic blocking substances, dopamine antagonists, an antihistamine, reserpine and a 5-hydroxytryptamine antagonist as well as the inhibitors of catecholamines, 5-hydroxytryptamine and acetylcholine synthesis upon convulsions produced by nicotine, which was similarly injected. Mecamylamine and hexamethonium but not atropine, scopolamine, yohimbine, phenoxybenzamine, tolazoline, propranolol, practolol, chlorpromazine, haloperidol, antazoline and methysergide abolished the convulsions evoked by nicotine. Furthermore, reserpine, but not 6 hydroxydopamine, as well as 5,6-dihydroxytryptamine and hemicholinium blocked the convulsions caused by nicotine. It appears, therefore, that the convulsions produced by nicotine are mediated through central nicotinic receptors. However, the depressed catecholaminergic, 5-hydroxytryptaminergic and histaminergic mechanisms induced by reserpine can also suppress the convulsions evoked by nicotine. PMID- 2874566 TI - Discriminative profile of MDMA. AB - Groups of rats were trained to discriminate the stimulus properties of dopaminergically and/or serotonergically active drugs, viz., apomorphine, fenfluramine, tetrahydro-beta-carboline (THBC) and l-cathinone. Once trained, these animals were given several doses of drugs used in training and dose response relationships and ED50 values were generated. Subsequently, each group of trained rats was administered various doses of 3,4 methylenedioxymethamphetamine (MDMA) to test generalization of the interoceptive cue of the drug used for training to MDMA. Rats trained to fenfluramine, THBC, and l-cathinone were observed to discriminate MDMA in a manner similar to the drug state to which they had been trained. Analysis of dose-response curves suggested that MDMA may be acting both as an indirect dopaminergic agonist and as a serotonergic receptor agonist. This duality of effect of MDMA has been evidenced by other studies and may account for its present abuse potential. PMID- 2874567 TI - The effects of some atypical neuroleptics on apomorphine-induced behaviors as a measure of their relative potencies in blocking presynaptic versus postsynaptic dopamine receptors. AB - The effects of the atypical neuroleptics clozapine, thioridazine and sulpiride on behaviors induced by apomorphine were recorded, using a time-sampling observational paradigm. A low dose of apomorphine (0.1 mg/kg, SC) produced hypomotility. Of the neuroleptics tested, only sulpiride antagonized this hypomotility. Apomorphine in higher doses (0.2-1.0 mg/kg, SC) produced stereotyped behaviors (sniffing down and licking or gnawing). All three atypical neuroleptics antagonized stereotypy. The effects of sulpiride on apomorphine induced hypomotility and stereotypy are consistent with the notion that this drug has strong presynaptic and weak postsynaptic blocking effects at dopamine receptors. The mechanisms of action of clozapine and thioridazine may be different from that of sulpiride. Perhaps the anticholinergic activities of these drugs mediate some of their behavioral effects. The effects of these atypical neuroleptics on apomorphine-induced stereotypy are opposite in direction to their effects on amphetamine-induced stereotypy, suggesting that these two behavioral patterns are not measures of the same neural process. PMID- 2874568 TI - The effects of cysteamine on dopamine-mediated behaviors: evidence for dopamine somatostatin interactions in the striatum. AB - The effects of prior treatment with cysteamine, a drug which appears to deplete selectively the neuropeptide somatostatin, on apomorphine-induced stereotypy and amphetamine-induced locomotor activity and conditioned place preferences were investigated. Twelve hours following systemic cysteamine injections apomorphine induced stereotypy was attenuated and striatal somatostatin levels were reduced by half. Systemic cysteamine also decreased the motor stimulant effects of amphetamine, without influencing the rewarding properties as determined by the conditioned place preference procedure. Direct injections of cysteamine into the nucleus accumbens also decreased the locomotor response to amphetamine, and produced a local reduction in somatostatin levels in the accumbens. Cysteamine did not appear to alter monoamine turnover in the striatum after either systemic or intra-accumbens injections. These results suggest that somatostatin in the nucleus accumbens and caudate-putamen modulates the motor, but not the reinforcing properties of dopaminergic drugs, possibly via an action postsynaptic to dopamine-releasing terminals. Furthermore, it is evident from these results that cysteamine is an important tool with which to study the central actions of somatostatin. PMID- 2874569 TI - Acute administration of MIF-1 or Tyr-MIF-1 inhibits haloperidol-induced catalepsy in rats. AB - The effects of MIF-1 (Pro-Leu-Gly-NH2) and Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) on haloperidol-induced catalepsy were studied in order to examine the influences of both peptides on central dopaminergic function. In the first experiment, several variables were tested. It was found that the optimal effect was achieved with a dose of 1.0 mg/kg haloperidol injected SC an hour before testing for catalepsy and 1.0 mg/kg MIF-1 injected SC 30 min before testing. In the second experiment, Tyr-MIF-1 as well as MIF-1 were injected as single injections at four doses. Catalepsy was inhibited in an inverted U-shape dose-response relationship with the maximal effect of each peptide occurring at 1.0 mg/kg. The results indicate that when careful attention is given to dose, both MIF-1 and Tyr-MIF-1 can activate dopaminergic neuronal activity after acute administration. PMID- 2874570 TI - 6-Hydroxydopamine-induced aggression in cats: effects of various drugs. AB - The effects of intracerebroventricular injections (ICV) in the unanesthetized cat of antimuscarinic drugs, ganglionic blocking agents, alpha and beta adrenergic blocking substances, dopamine and 5-hydroxytryptamine (5-HT) antagonists, and an antihistamine on aggressive behavior produced by 6-hydroxydopamine injected similarly was investigated. It was found that atropine, hyoscine, hexamethonium, mecamylamine, yohimbine, phenoxybenzamine, propranolol, practolol, chlorpromazine, haloperidol, antazoline and methysergide exerted virtually no effect on the pattern of aggressive responses evoked by ICV 6-hydroxydopamine. It is thus concluded that the aggressive behavior induced by 6-hydroxydopamine is not related to the release of acetylcholine, norepinephrine, dopamine, histamine or 5-hydroxytryptamine from endogenous storage sites in the brain. PMID- 2874571 TI - Increase in atrial contractility induced by PGE2 in diabetic rats. AB - Contractile response to exogenous prostaglandin E2 (PGE2) was studied in auricles from normal and acutely-diabetic (streptozotocin-treated) rats. In normal atria, PGE2 induced a biphasic inotropic effect negative at low concentrations and positive at higher ones. In diabetic, PGE2 only elicited a positive inotropic action which was greater in efficacy and potency than in normal controls. Incubation of diabetic atrial preparations with alpha-adrenoceptor antagonists (phentolamine, phenoxybenzamine or Prazosin) diminished the prostaglandin effect. However, blockade of beta-adrenoceptors with propranolol did not modify the response. Blockers of arachidonic acid metabolism via cyclo-oxygenase (indomethacin and acetylsalicylic acid) or via lipoxygenase(s) (nordihydroguaiaretic acid and dithizone) were able to reduce the positive inotropism of PGE2. A significant blockade of the stimulant action of PGE2 was seen in the presence of inhibitors of thromboxane synthesis (L-8027 and imidazole). These results suggest that in diabetic atria PGE2 effect could be associated to an involvement of cardiac alpha-adrenergic stimulation which promotes endogenous arachidonic acid release with diversification of its metabolism towards cyclo- and lipoxygenase(s)- pathway and direct to an increased thromboxane formation which could account for the positive inotropic effect induced by PGE2. PMID- 2874572 TI - 1-(2-Pyrimidinyl)-piperazine as active metabolite of buspirone in man and rat. AB - Buspirone (BP), a newly developed antianxiety agent, forms 1-(2-pyrimidinyl) piperazine (PmP) during its biotransformation in rats and man. After oral administration of pharmacologically effective doses of BP-hydrochloride to rats (1 and 10 mg/kg), the metabolite appears in significant amounts in body fluids and tissues; it is highly concentrated in the central nervous system, the brain to-plasma concentration ratios being approximately 5 at the time of the maximum concentrations (Cmax). In man given the anxiolytic dose (20 mg) of BP the metabolite reaches higher plasma Cmax values than its parent drug. Its plasma elimination t1/2 is more than double that for BP. These results, together with the fact that PmP is biochemically and pharmacologically active, suggest that the metabolite may contribute significantly to the central effects of the parent drug. PMID- 2874573 TI - Seasonal variation in opioid modulation of feeding in the 13-lined ground squirrel. AB - Opioids are well recognized to modulate ingestive behaviors in a variety of species. To study the potential role of opioids in the alteration of ingestive behaviors that occur prior to hibernation, we have administered opiate agonists and the antagonist, naloxone, to the 13-lined ground squirrel (Spermophilus tridecemlineatus) during periods when they were hyperphagic and hypophagic. Naloxone consistently reduced feeding during both phases of the feeding cycle. Hypophagic animals, however, were 10 times more sensitive to the effects of naloxone. The effect of the opiate agonists (morphine and butorphanol, 1 and 10 mg/kg) on feeding also varied between seasons. The low dose of morphine produced a slight, but significant increase in feeding at one hour in hyperphagic animals, while the high doses tended to decrease feeding. When administered to hypophagic animals, feeding was decreased by both doses of each agonist. Immunoreactive (IR) dynorphin levels in the cortex, hypothalamus and striatum were higher during the hypophagic phase compared with the hyperphagic phase. These data indicate that the 13-lined ground squirrel possesses an opiate sensitive feeding system which is affected by season. PMID- 2874574 TI - The unique conjugation system of IncHI3 plasmid MIP233. AB - The conjugation system of the IncHI3 plasmid MIP233 was studied using a transfer derepressed Tn5-insertion mutant. The conjugative pili of this plasmid were short pointed rods resembling rigid pili, with a well-defined modal length. Unlike plasmids with rigid pili, the MIP233 mutant mediated a surface + liquid conjugation system. The pili were serologically different from all known pilus types including H pili, and did not act as receptors for any known pilus-specific bacteriophage. They converted the surface conjugation system of RP4 to a surface + liquid one. Antiserum to pili of the mutant plasmid inhibited transfer of the wild-type plasmid MIP233, demonstrating that it contained only one transfer system. PMID- 2874575 TI - Reconstruction of heel and sole defects by free flaps. AB - One latissimus dorsi musculocutaneous flap and five radial forearm flaps were used in reconstruction of weight-bearing parts of the heel and sole, the follow up period being 7 to 38 months. Additional injuries such as forefoot amputations or amputations of the other leg were present in four patients. There was no flap loss. The latissimus dorsi flap proved to be too bulky and showed recurrent ulcerations, several reoperations were necessary, and definite healing has not occurred. The five forearm flaps gave good results, with a walking range from 2 hours to unimpeded walking. Complications included fissuring at the edges of one large flap and a local infection which was successfully treated. Cutaneous sensation returned in all but one flap, where it was reduced preoperatively due to a meningomyelocele. The results indicate that the fasciocutaneous radial forearm flap should be taken into consideration for reconstruction of weight bearing areas of the heel and sole. Shortcomings of this flap include an unsightly donor defect and possible hair growth on the flap. PMID- 2874576 TI - [Prolactin and the function of the central nervous system]. PMID- 2874578 TI - Serial dexamethasone suppression tests in psychiatric illness: Part I. A study in schizophrenia and mania. AB - Weekly dexamethasone suppression tests (DSTs) were performed in 15 patients with schizophrenia (n = 12) and mania (n = 3) until clinical response. At initial evaluation, 53.4% of the patients were nonsuppressors, and 93.3% showed nonsuppression at least once during the treatment period. There was a tendency for DST results to normalize coincident with clinical improvement, although single peaks of DST nonsuppression occurred in several patients irrespective of clinical course. The tests did not prove useful as predictors of recovery or relapse. DST nonsuppression occurred significantly more often in severely ill patients than in moderately ill patients or in patients after recovery, emphasizing the effects of nonspecific stress factors and/or severity of illness on the DST. The cutoff point, established on the basis of DST results in 67 healthy controls, was lower than in other studies, and nonsuppression among healthy controls was associated with low dexamethasone serum levels. PMID- 2874577 TI - Treatment patterns of young chronic schizophrenic patients in the era of deinstitutionalization. AB - A retrospective longitudinal treatment utilization study of 56 young chronic schizophrenic patients who began their treatment careers during the deinstitutionalization era was carried out covering all psychiatric services provided to each patient since first treatment. The group was primarily male and was characterized by histories of drug abuse and violence. Treatment utilization was heavy, discontinuous, and episodic with these patterns intensified for patients with histories of drug abuse. The majority of the group became "long stay" hospital residents. The clinical and mental health policy implications of these findings are discussed and further research is suggested. PMID- 2874579 TI - Cognitive event-related potential correlates of schizophrenia. PMID- 2874580 TI - An overview of cocaine use and abuse. PMID- 2874581 TI - Disinhibitory effects of buspirone and low doses of sulpiride and haloperidol in two experimental anxiety models in rats: possible role of dopamine. AB - Low doses of buspirone, haloperidol and sulpiride were compared with diazepam in two experimental models of anxiety in rats. In a conflict test, 0.6 and 1.2 mg/kg buspirone, 0.05 and 0.10 mg/kg haloperidol and 0.5 mg/kg sulpiride significantly increased punished responding. Buspirone 1.2 and 2.5 mg/kg significantly reduced the number of unpunished responses while haloperidol and sulpiride at the doses tested had no effect. Effects on punished responding were seen in a narrow dose range and were less pronounced with these drugs than with diazepam. Similar results were obtained with rats', activity in the two-compartment exploratory test. At doses causing no change in the locomotion of rats in photocell activity cages, buspirone (0.1 mg/kg), haloperidol (0.025-0.100 mg/kg) and sulpiride (0.5 1.0 mg/kg) significantly increased the number of crossings between the two compartments. Again, the peak effects were small when compared with the effect of diazepam and the active dose range was very narrow. Apomorphine 0.2 mg/kg SC significantly counteracted the effect of 0.1 mg buspirone and 1.0 mg/kg sulpiride in the two-compartment exploratory test with no effect on 2.5 mg/kg diazepam. The data show that buspirone, in a narrow dose range, shows disinhibitory effects in experimental models of anxiety. Similar effects are shown by low doses of haloperidol and sulpiride. It is suggested that buspirone and sulpiride produce these disinhibitory effects by blocking particular dopamine receptors in the brain, possibly those located in the nerve terminals, but it is likely that other mechanisms, particularly serotonin, are involved in the effects of buspirone in anxious states. PMID- 2874582 TI - The staircase test: some evidence of nonspecificity for anxiolytics. AB - In the staircase test, a naive mouse is placed in a Plexiglas chamber containing a five-step staircase, and the number of rearings and steps climbed are recorded for 3 min. A claim for drug-class specificity has been made because conventional anxiolytics reduced rearings at doses that did not reduce steps climbed, while non-anxiolytics affected both measures in parallel. In the present study chlordiazepoxide, meprobamate, and ethanol registered the expected true positive effect by reducing rearings at doses that did not reduce steps climbed. Nicotine, which has some clinical anxiolytic action, registered a small true positive. The benzodiazepine anxiolytic alprazolam reduced both measures, a false negative, although it reduced rearings more than steps climbed. The putative novel anxiolytics CGS 9896, ketanserine, and tracazolate registered negatives, as did the known clinical anxiolytic buspirone. The non-anxiolytics phencyclidine and phenacetin registered true negatives, but morphine registered a clear false positive. The anxiogenics FG 7142 and pentylenetetrazol produced no significant effects. Because of the equivocal false negative for alprazolam, the clear false negative for buspirone, and the clear false positive for morphine, we concluded that the test lacks the degree of therapeutic-class specificity previously proposed but may still be useful in basic research. PMID- 2874583 TI - Stretched attend posture, a non-social form of ambivalence, is sensitive to a conflict-reducing drug action. AB - Based upon the ethological element "stretched attend" to a conspecific, which reflects ambivalence between approach and avoidance in a social context, a simple, non-social behavioral method for studying conflict behavior in mice was investigated. Thus, stretched attend posture (SAP) and other behavioral acts were measured in untreated or drug-treated mice which were individually placed on a perforated platform previously rubbed with foreign male urine and boluses. In naive, untreated mice, the occurrence of SAP was partly housing- and lighting dependent. After repeated exposure to the test situation, untreated mice showed less SAP, whereas static behavior (immobility and activity at rest) was increased. After single oral treatment with diazepam, clobazam or phenobarbital, SAP was reduced, whereas static behavior or "going forwards in SAP" was increased. Chlorpromazine and imipramine did not influence SAP. In naive mice, single IP injection of pentylenetetrazol did not significantly increase SAP. The similarity in the behavioral response between experienced, untreated mice and naive animals treated with diazepam, clobazam, or phenobarbital suggests that drug-treated mice behaved as if they were already familiar with the test situation. The latter drug-induced changes are consistent with data obtained in animal models which are based upon the measurement of behavioral inhibition. Under the present test conditions, pentylenetetrazol did not show "anxiogenic" properties. Nevertheless, the SAP test, based primarily on the measurement of the ambivalence element, offers a simple procedure for examining the conflict reducing properties of drugs, dispensing with the need of noxious stimuli or prior training. PMID- 2874585 TI - Periarteritis nodosa mimicking an affective disorder. PMID- 2874584 TI - Response decrement patterns after neuroleptic and non-neuroleptic drugs. AB - Previous work has shown that administration of pimozide and other neuroleptic drugs can produce within-session response decrement patterns of appetitively reinforced behaviour. This phenomenon has been described as an extinction-like pattern of responding and used as evidence for the hypothesis that these drugs attenuate the rewarding properties of food, water and electrical stimulation of the brain. The present study was carried out to investigate within-session patterns of responding maintained by food presentation or shock avoidance after administration of a variety of neuroleptic and non-neuroleptic drugs. Haloperidol, metoclopramide, pimozide and butaclamol produced within-session response decrements of both food-reinforced lever pressing and one-way shock avoidance. The atypical antipsychotic drug clozapine did not consistently produce similar effects nor did the alpha-adrenoceptor agonist clonidine, the opiate agonist morphine, the benzodiazepine anxiolytic chlordiazepoxide and the muscle relaxant methocarbamol, although all these drugs were tested up to doses which markedly disrupted responding. Thus, within-session response decrement patterns are a characteristic effect of dopamine-blocking neuroleptic drugs. However, because of the generally similar effects of these drugs on appetitively- and aversively-motivated behaviour, these effects are probably best interpreted as actions on motor, rather than motivational, mechanisms. PMID- 2874586 TI - Q-T prolongation in psychiatric outpatients. PMID- 2874587 TI - Dipeptidyl peptidase IV in human T-lymphocytes: cytochemical and histochemical investigations in patients with non-Hodgkin's lymphoma. AB - The occurrence of DP IV-reactive T-lymphocytes in patients with aleukemic non Hodgkin's lymphoma (NHL) was studied using mononuclear cells (MNC) obtained from peripheral blood, bone marrow aspirates and lymph nodes, as well as cryostat sections of lymph nodes. These patients were found to have a reduced percentage of DP IV-reactive T-cells in MNC from peripheral blood (32%) in comparison to a healthy control group (44%). Patients suffering from chronic lymphocytic leukemia (B-type CLL) also had significant reduced level of DP IV-reactive cells (5% DP IV reactive cells in the MNC fraction corresponding to about 40% of the T-cell fraction) in peripheral blood, whereas in lymph nodes of these patients 72% of the T-cells expressed DP IV. Among the MNC from lymph nodes of patients with aleukemic NHL about 24% were DP IV positive corresponding to 57% of the T-cell fraction. MNC from bone marrow of these patients were shown to contain about 21% T-lymphocytes and 18% DP IV-reactive cells. In addition to that, cryostat sections of lymph nodes were analysed for the occurrence and distribution of DP IV. In normal lymph nodes and tonsils DP IV-positive cells have the same distribution pattern like T-cells in general. In lymph node sections from patients with NHL of B-cell origin, such as B-CLL, the DP IV-reactive cells are sparsely and irregularly distributed and displaced by the proliferating B-cells. It is concluded that DP IV is a useful marker not only for T-lymphocytes in proliferating lymphatic tissue but also an indicator of imbalances between regulatory T-cell subsets in peripheral blood. PMID- 2874588 TI - [Somatostatin in lamprey brains (Lampetra planeri Bloch)]. AB - In the brain of larval and adult lampreys (Lampetra planeri Bloch) a distinct somatostatin system using somatostatin antiserum with the unlabeled peroxidase antiperoxidase technique was demonstrated. The immune reactive perikarya are localized in the nucleus ventralis hypothalami and they are restricted to this nucleus without exception. A small number of immune positive efferences invades the commissura praeinfundibularis. In the neurohypophysis localized caudally from this commissure and in the adenohypophysis no somatostatin fibres could be visualized. Most of the efferences leave the hypothalamus as exohypothalamic fibres and form a system of somatostatin fibres which extends from the telencephalon to the medulla oblongata. Regionally, this system is organized in a net-like manner. PMID- 2874589 TI - [Aspartate aminotransferase activity high affinity (3H) glutamate/(3H) aspartate uptake in rat nervous tissue in postnatal development]. AB - The regional distribution and cellular localization of aspartate aminotransferase (AspAT) as a glutamate and aspartate metabolizing enzyme was studied in the hippocampal formation, in dorsal root ganglia, and in superior cervical ganglia during the postnatal development of the rat. At birth, in all neuronal tissues studied the enzyme activity was rather low. Whereas in the dendritic layers of the hippocampal formation enzyme levels rose strikingly during the first weeks of postnatal life, those of peripheral ganglia remained remarkably stable. The high affinity uptake of [3H]labelled L-glutamate and D-aspartate were studied in surface autoradiograms of incubated slices of hippocampal formation during postnatal development of the rat. Our data indicate that the postnatal development of high affinity uptake capacity is parallel to the increase of histochemically demonstrable AspAT activity in the hippocampal formation suggesting that the enzyme may be involved in glutamate/aspartate neurotransmitter metabolism. PMID- 2874590 TI - Treating alcohol, barbiturate, and benzodiazepine withdrawal. PMID- 2874591 TI - Somatostatin in the central nervous system: physiology and pathological modifications. AB - Since its discovery, at the beginning of 1973, somatostatin's multiple actions, in relation to its wide anatomical distribution have been widely documented. Its biochemical pathways have been elucidated with the discovery of other molecular forms as well as the mechanisms of its neuronal release. However, no definite proof is available concerning a neurotransmitter role for any peptide of the somatostatin family other than somatostatin-14. The precise determination of the roles of somatostatin in brain are still hampered by the poor pharmacology of the peptide. New tools are badly needed and in particular a true antagonist at the receptor site. The mechanisms of action of somatostatin are now well under way at least in the pituitary model. More information should come from this model and be applied to brain cells in vitro. The greatest challenge of somatostatin brain function lies in its role in the pathophysiology of neurological diseases such as Alzheimer's dementia and Huntington's disease. Nature has been using somatostatin related molecules since inhibitory control was first needed in cell functions. Time will tell us if somatostatin is really an old peptide involved in senile dementia. PMID- 2874592 TI - [Portal hypertension and esophageal varices. A problem for today and always]. PMID- 2874593 TI - [Diagnosis of alcoholism. A challenge for physicians]. PMID- 2874594 TI - [Comparative clinical study between vecuronium bromide and pancuronium bromide]. PMID- 2874595 TI - [Comparative study of the behavior of gamma-glutamyl transpeptidase in hepatobiliary pathology]. PMID- 2874596 TI - [Role of hyperlipoproteinemia in the increase of gamma-glutamyl transpeptidase in hepatopathies: results of treatment]. PMID- 2874597 TI - [The psychology of health and dentistry. Evaluation of psychological technics for anxiety, attitude, patient cooperation and timing of dental treatment]. PMID- 2874598 TI - In vivo and in vitro studies on fetal toxicity of benzodiazepines in rats. AB - In this study, we investigated whether the intensity in the embryotoxicity of benzodiazepines was related to maternal and fetal blood levels and also to their high binding to the fetoplacental structures in rats. Maternal and fetal levels of nitrazepam (NTZ) and nimetazepam were higher than the diazepam level after oral administration of these drugs (100 mg/kg). In vitro, the affinity of the drugs for the fetus corresponded to the drug levels in the maternal serum and fetus. In the embryo culture, NTZ had no direct teratogenicity but had embryocidal activity. On the contrary, the in vivo maternal serum treated with NTZ possessed both activities. From the above facts, and since there was no change in the in vivo embryotoxicity as a result of phenobarbital, it was suggested that the embryocidal activity of NTZ may be due to changes of maternal function depended upon the maternal serum. PMID- 2874600 TI - [A 24-year-old woman with seronegative arthritis and neurologic changes]. PMID- 2874599 TI - Medullary effects of nicotine and GABA on tracheal smooth muscle tone. AB - Airway tone can be modulated centrally by the brain as well as by peripheral receptors. In part these changes in airway caliber seem to be secondary to changes in respiratory activity. Since structures near the ventrolateral medullary surface (VMS) can produce profound effects on respiration, it seems reasonable to believe that they might also be capable of modifying tracheal tone. In this study we examined the effects of two agents with respect to their action on tracheal tone: nicotine, a respiratory stimulant when applied to the VMS, and gamma aminobutyric acid (GABA), a respiratory depressant when similarly administered. In chloralose anesthetized, paralyzed, artificially ventilated cats, tracheal tone was assessed by measuring pressure changes in a rostral bypassed segment of the trachea, while phrenic nerve activity was examined simultaneously. Nicotine administered on the intermediate area of the VMS both before and after carotid sinus denervation increased phrenic activity and induced constriction of the rostral tracheal segment. The response to nicotine could be blocked by application of a nicotine antagonist, hexamethonium, or prior local administration of lidocaine to the VMS. Activation of GABAergic receptors by application of GABA on the intermediate area of the VMS markedly reduced respiratory activity and nearly abolished the increased tracheal tone produced by inhalation of 7% CO2 in O2. The effects of GABA were eliminated by the prior administration to the VMS of bicuculline, a GABA receptor antagonist. These results indicate that structures located on the ventral surface of the medulla which affect breathing may also play a significant role in the regulation of airway smooth muscle tone. PMID- 2874601 TI - [The biology of schizophrenia: current status and perspectives of its knowledge]. PMID- 2874602 TI - [A 26-year-old male with mental retardation, habitus marfanoid, cold thyroid nodule and digestive tract hemorrhage]. PMID- 2874603 TI - [Cryptorchism: a multidisciplinary approach]. PMID- 2874604 TI - [Experimental and clinical bases for the respiratory action of almitrine]. PMID- 2874605 TI - Adoptive immunotherapy of cancer with immune and activated lymphocytes: experimental and clinical studies. AB - Recent studies of passive adoptive immunotherapy of experimental tumors indicate that histologically different neoplasms can be cured by this procedure in mice, rats and guinea pigs. In this paper two main approaches of adoptive immunotherapy with lymphocytes are considered. One which makes use of specific tumor-immune cells and is applicable to immunogenic tumors, and the other which uses activated (allostimulated and/or IL-2-activated) lymphocytes and is applicable to immunogenic and non-immunogenic neoplasms. Experimental models of both approaches and results provided by them are reviewed. These studies indicate that transfer of tumor-reactive lymphocytes with or without the combined administration of IL-2 into syngeneic tumor-bearing animals can lead to the eradication of a disseminated neoplasia when certain conditions are met. In particular, it was found that high tumor burdens, delay of treatment and low number of transferred lymphocytes can adversely affect the results. It has also been shown that the therapeutic effect of treatment with anti-cancer drugs or irradiation may be significantly improved by the addition of adoptive immunotherapy. The successful treatment of immunogenic tumors often requires the inhibition of suppressor lymphocytes by Cy or irradiation. Non-immunogenic tumors can be successfully treated only by providing activated lymphocytes and high doses of IL-2. Recent findings of few available human studies of adoptive immunotherapy are also reviewed, and the problems of toxicity and possible therapeutic effects of infusion of autologous, activated lymphocytes and IL-2 are discussed. PMID- 2874606 TI - Heterogeneity of B cell growth factor (BCGF)-producing T cells in humans. Clonal analysis of BCGF-producing cells within T4+ and T8+ subsets and evidence for the involvement of different growth factors in different BCGF assays. AB - Human peripheral blood T cells were cloned under conditions allowing the clonal expansion of virtually all T cells. Clones derived from T4+ or T4- (T8+) subsets were screened for their ability to induce B cell proliferation either in the Staphylococcus aureus Cowan-I (SAC)-driven assay or in the costimulation assay based on the use of anti-mu antibodies. BCGF activity in the SAC- and in the anti mu-driven system was displayed by 13% and 15% T8+ clones, respectively, while 74% and 79% T4+ clones had BCGF activity in the same assay. SN of clones with BCGF activity were further screened for their susceptibility to the inhibition by CM 269 (anti-IL-2 receptor) monoclonal antibody. All clones were inhibited in the SAC assay, whereas several clones were partially or totally resistant to inhibition in the anti-mu assay. Nine of such non-inhibited clones were further analyzed for their ability to produce gamma-IFN (known to act as a BCGF) and IL 2: six of them were found to produce gamma-IFN, while none produced any detectable IL-2 activity. PMID- 2874607 TI - The nucleus of the solitary tract: a review of its anatomy and functions, with emphasis on its role in a putative central-control of brain-capillaries permeability. PMID- 2874608 TI - [Neurotensin]. PMID- 2874609 TI - [Presynaptic inhibition and facilitation]. PMID- 2874610 TI - Molecular structure and absolute configuration of the diterpene lactone, praelolide. AB - Praelolide is a new compound which was isolated out from the gorgonian, Menella praelonga (Ridley), collected from the South Sea of China at Zhanjiang, Guangdong. The molecular formula is C28H35O12Cl. The research result by X-ray diffraction method on the crystal structure is presented. The compound is orthorhombic with space group P2(1)2(1)2, cell dimensions a = 16.936, b = 16.709, c = 10.333 A, and Z = 4. The structure has been solved by direct method and refined to R = 0.055 for 2257 unique observable reflexions by least-squares. The molecule is composed of the major conformational isomer in which the three main rings (a six-membered ring, an eight-membered ring, a six-membered ring) take separately the form of chair-chairboat-chair, a five-membered actone ring, a C1 substitution, 4 acetate groups, and a three-membered epoxide ring. The absolute configuration of the molecule has also been determined by statistics (R factor ratio R = 1.012) and Bijvoet pairs observation. For 30 pairs of the greatest anomalous contributions the residuals are R'(+) = 0.057 for the first enantiomorph and R'(-) = 0.005 for the second one, so the latter should unambiguously correspond to the absolute configuration of the molecule. PMID- 2874611 TI - Transplantation of fetal hematopoietic stem cells in utero: the creation of hematopoietic chimeras. AB - Transplantation of normal, immature, fetal hematopoietic cells into a preimmune fetal recipient with a congenital hemoglobinopathy may allow partial reconstitution of normal hemoglobin production without the complications associated with postnatal bone marrow transplantation (immunosuppression and the occurrence of graft versus host disease). In order to test this hypothesis the naturally occurring polymorphism at the beta-hemoglobin locus of the sheep was used as a marker for engraftment and hematopoietic chimerism. Intraperitoneal injection of allogeneic fetal stem cells into normal fetal lambs resulted in hematopoietic chimerism in three of four surviving recipients. This chimerism has been sustained for 6 months after birth and 9 months after engraftment, without evidence of graft versus host disease, and without the use of immunosuppressive therapy. PMID- 2874612 TI - Blood value changes in flavivirus-inoculated Macaca fascicularis monkeys. AB - Blood values were analysed in eighteen cynomolgus monkeys on pre-and post neurovirulence testing of dengue-2 and yellow fever vaccine viruses, dengue-2 parental and Japanese encephalitis viruses. Certain changes between blood chemistry, hematology and serology were observed and briefly discussed. PMID- 2874613 TI - Susceptibility of Mansonia mosquitoes to subperiodic Brugia malayi and Brugia pahangi. PMID- 2874614 TI - A survey for natural vectors of Dirofilaria immitis in Chiang Mai Province, northern Thailand. PMID- 2874615 TI - Medication as a potential cause of depression. AB - Many different drugs have been reported to cause depression. The substantive literature is reviewed, with particular attention to antihypertensive and cardiac drugs, oral contraceptives, levodopa and major tranquilizers. The nature of the relationship between physical illness, therapeutic drug use and the potentiation or precipitation of depression is explored. PMID- 2874616 TI - [A study of the relationship between the occurrence of P-fimbriae and hemolysin production in Escherichia coli causing extraintestinal infections and the infectious site]. PMID- 2874617 TI - [Quantitative determination of spot size of dendrobine in thin-layer chromatography for Dendrobium nobile Lindl cultivated on trees]. PMID- 2874618 TI - The use of somatostatin and its analogs in the treatment of surgical disorders. AB - Somatostatin is a naturally occurring peptide with a wide spectrum of biologic actions, most of which are inhibitory in nature. It has wide distribution, and within the gastrointestinal tract is is found in the pancreas, the stomach, intestinal mucosa, and myenteric neurons. It appears to function as a classic circulating hormone, as well as both a paracrine or locally acting agent and a neurocrine agent. Because of its inhibitory actions on gut endocrine, secretory, and motor functions, it has potential applicability in the treatment of a variety of disorders of interest to the surgeon. Indeed, it has been used successfully in the management of upper gastrointestinal hemorrhage, secretory diarrhea, short bowel syndrome, pancreatitis, gastrointestinal fistulas, and peptide-secreting tumors of the gut (apudomas). This review discusses physiology, pathophysiology, and therapeutic applications of somatostatin that may be important in surgical practice. PMID- 2874619 TI - [Changes in plasma lipid levels after the administration of beta adrenoblockaders: possible advantages of natural sympathomimetic activity]. PMID- 2874620 TI - [Current drug therapy of chronic ischemic heart disease]. PMID- 2874621 TI - [Effect of the complex treatment of stable stenocardia on the status of the prostacyclin-thromboxane system]. AB - Raised function of platelets with an increase in their aggregation activity in vitro and an increase in spontaneous intravascular activation as well as imbalance of the prostacyclin-thromboxane system with a shift to the predominance of proaggregation agents were detected in CHD patients after myocardial infarction suffering from stable angina. An inhibiting effect of beta-adrenergic receptor blocking agents and acetylsalicylic acid on the synthesis of thromboxane A2 was observed. No marked effect of dipyridamole on the prostacyclin-thromboxane system was noted. PMID- 2874622 TI - [Remote results of the surgical and conservative treatment of ischemic heart disease patients with a lesion of the left coronary artery trunk]. AB - A study was made of the results of surgery of 37 patients and conservative therapy of 90 patients (including 53 inoperable cases) with coronary heart disease with the involvement of the left main coronary artery. Lethality in a long-term period was 16.2% in the operated patients and 45.6% in the inoperable patients. A considerable improvement of the status with the lessening or disappearance of angina attacks was noted in 27 operated patients (87%), a stable improvement of ECG at rest and a considerable increase in exercise tolerance were noted in 11 patients. There was no considerable improvement of the status in the inoperable patients, a slight decrease in the number of attacks was noted in 22% of the patients only, impairment of ECG at rest was noted in 52%, exercise tolerance decreased in most of the patients. In the operated patients the 7-year survival rates according to actuarial curves were 81%, in the operable but receiving conservative therapy 47% and in the inoperable patients 34%. PMID- 2874623 TI - Leydig cell hyperplasia in fetal mice treated transplacentally with ethinyl estradiol. AB - Pregnant female mice were given ethinyl estradiol on days 11 through 17 of gestation. On day 18 the dams were killed and the male fetuses were examined for testicular differentiation. Three of 12 males from dams treated with the highest dose of ethinyl estradiol showed cryptorchid testes with uterine tubes. Light and electron microscopic evaluation of the testes, both cryptorchid and normal, demonstrated foci of hyperplasia of Leydig cells showing cytoplasmic and nuclear pleomorphism, increase in lipid droplets, and decrease in smooth endoplasmic reticulum and ribosomes when compared to testes from control fetal mice. Morphometric determinations of the testes indicated that the number of Leydig cells in a unit area (mm2) in the interstitial tissue showed a dose-response relationship to ethinyl estradiol in the normal testes. The number of Leydig cells in the testes exposed to the highest dose of estrogen showed a significant difference between cryptorchid and normal testes: the former had fewer Leydig cells than the latter. These morphological observations indicate that hyperplasia of Leydig cells of fetal mouse testis at term can be induced by transplacental treatment with ethinyl estradiol and suggest that a malignant transformation into a Leydig cell tumor is possible. PMID- 2874624 TI - Inhibition of metabolic cooperation by the anticonvulsants, diphenylhydantoin and phenobarbital. AB - High densities of 6-thioguanine-sensitive Chinese hamster V79 cells reduce the recovery of co-cultured 6-thioguanine-resistant cells through a form of intercellular communication (metabolic cooperation). Diphenylhydantoin and phenobarbital, suspected human and animal teratogens and tumor promoters, were able to inhibit intercellular communication at noncytotoxic doses. A potentiation was observed when a mixture of the two chemicals was used. PMID- 2874625 TI - Carcinogenicity bioassays of bromoacetaldehyde and bromoethanol--potential metabolites of dibromoethane. AB - 1,2-Dibromoethane (DBE) and two of its potential metabolites, bromoethanol (BE) and bromoacetaldehyde (BA), were tested for carcinogenicity in male and female B6C3F1 mice using 30 animals of each sex per group. The carcinogen DBE was included in this assay as a positive control. The compounds were administered in distilled drinking water using equimolar concentrations, 4 mmol, of the chemicals. The dose chosen was based on subchronic bioassays of three months' duration. The chronic tests were continued for approximately 450 days in the case of DBE and approximately 560 days for both BE and BA. DBE induced squamous carcinomas of the forestomach in 22 females and 26 males and squamous papillomas of the esophagus in 3 females. BE induced squamous papillomas of the forestomach only in 10 females and 9 males. BA did not induce a significant incidence of tumors of the forestomach. Significant tumor incidences at other sites were not observed in any groups including the distilled water control group. Based on these findings, it is unlikely that BE or BA are activated carcinogenic intermediates of DBE. PMID- 2874626 TI - Increased carcinogen metabolism and survival of retrovirus-infected Fischer rat embryo cells following repetitive carcinogen treatment. AB - The carcinogens N-2-acetylaminofluorene (AAF) and diethylnitrosamine (DEN) often give negative results when tested in the Fischer rat embryo cell survival assay with the standard single 72-hour regimen, whereas another carcinogen, benzo(a)pyrene [B(a)P], may yield varied results between different laboratories and may require relatively high concentrations (compared with other polycyclic aromatic hydrocarbons) for a positive result to occur. Enhanced survivals (compared with controls) were 56% or less with these carcinogens. In place of the standard single 72-hour treatment with test chemical, the cells were exposed to three consecutive 24-hour treatments. The amount of B(a)P metabolized during the last of the three 24-hour treatment periods was 3.2 times greater than that during the first 24-hour period, indicating that an induction effect occurred. Furthermore, the total amount of metabolites of B(a)P formed with repetitive treatments was 2.1 times greater than with a single 72-hour treatment. The total amount of AAF metabolites formed with repeated treatments was 1.6 times greater than with the single treatment regimen, although no induction effect was observed between treatment periods. Survival enhancement with the repetitive regimen increased to 181% with B(a)P, 172% with AAF, and 188% with DEN. With benzo(e)pyrene, anthracene, and pyrene, enhanced survival was 14% or less following the single treatment regimen and did not increase following repetitive treatments. When the carcinogen cinnamyl anthranilate was tested using repetitive treatments, survival enhancement was more than 100% at three of six doses, versus less than 0% when the standard single treatment regimen was used. PMID- 2874627 TI - Teratogenicity of arotinoid ethyl ester (RO 13-6298) in mice. AB - Arotinoid ethyl ester (RO 13-6298) is a new and very potent retinoid that exerts a profound influence on epithelial and mesenchymal differentiation in doses 500 times lower than those of compounds of the first and second retinoid generation. In the present study the teratogenicity of arotinoid ethyl ester was investigated in NMRI mice employing different treatment schedules. Recording of abnormalities was performed on day 18 (day 0 = day of conception) according to Wilson and with cleared skeletal preparations. Intraperitoneal application of the drug at a dosage of 10 micrograms/kg/day for three consecutive days (days 9-11 or 12-14) caused severe malformations, particularly in the skeletal system and the cavernous organs. Skeletal elements were reduced in number, shortened, or abnormally shaped. Ossification was diminished. Atresia of anus and urethra were frequent. Single application of 200 micrograms/kg between days 8 and 14 also caused multiple and severe malformations. However, no stage-specific pattern of abnormalities was detectable. Some skeletal malformations indicated more or less vulnerable stages that were in concordance with special developmental steps. Others, however, seemed to be equally susceptible over a longer period, eg, rays 1 and 5 of the hand or foot and the development of the mandibular joints. The pattern of abnormalities caused by these very low doses of RO 13-6298 is comparable to that obtained with other retinoids and is achieved within the same relative dose-response range. Preconceptional treatment of the animals did not induce any malformations. PMID- 2874629 TI - The International Association of Environmental Mutagen Societies (IAEMS). PMID- 2874628 TI - Potentiation of chemically induced cleft palate by ethanol ingestion during gestation in the mouse. AB - The influence of ethanol consumption on cleft palate induction by methylmercury, cortisone, and retinyl acetate was investigated in Swiss white mice. Consumption of 20% ethanol throughout gestation significantly increased the incidence of cleft palate compared to water-fed mice, when methylmercury was given on four consecutive days (days 9-12, 5 mg/kg of body weight). Ethanol also increased the incidence of cleft palate in mice given retinyl acetate (3,400 or 5,100 IU) on day 12, compared to retinol acetate-treated mice given water, but did not affect cleft palate induction by cortisone (2.5 mg/d, days 8-11). Ethanol significantly reduced fetal weight in the presence or absence of the three teratogens, but the results do not support a hypothesis that growth retardation is directly responsible for the potentiating action of ethanol. It may be that ethanol acts to increase cleft palate induction by some teratogens by retarding fetal developmental processes. PMID- 2874630 TI - Comparative enzymatic acetylation of carnitine and choline by human placenta syncytiotrophoblast membrane vesicles. AB - Microvillous membrane vesicle preparations from the maternal surface of human placental syncytiotrophoblast were examined for the presence of carnitine and choline acetyltransferase activity. Radiometric assay for acetylcholine employed butyronitrile-tetraphenylboron extraction of the quaternary ions. Acetylcarnitine was assayed by anion exchange chromatography. The data reveal that carnitine is the primary substrate for the vesicle acetyltransferase enzyme(s), whereas choline appears to be a minor substrate. For acetylcarnitine synthesis, the Km is 0.749 mM carnitine and Vmax is 641 pmol X mg protein-1 X minute-1, respectively; for acetylcholine synthesis, the Km is 0.5 mM choline and Vmax is 53 pmol X mg protein-1 X minute-1, respectively. Approximately ten times more acetylated product was formed with carnitine than with choline. The carnitine-mediated reaction obeyed Michaelis-Menten kinetics, whereas the choline reaction exhibited anomalous behavior. Vesicle preparations were stable for 21 days at -80 degrees C. Preliminary studies on hypotonically lysed vesicles demonstrate that the acetyltransferase is particulate and is bound to the membrane of the vesicle. These findings demonstrate that carnitine acetyltransferase activity is in the plasmalemma membrane of the syncytiotrophoblast and suggest a role for this enzyme, analogous to the mitochondrial fatty acid shuttle system, in the maternofetal translocation of fatty acyl residues. PMID- 2874631 TI - Murine oocyte destruction following intraovarian treatment with 3 methylcholanthrene or 7,12-dimethylbenz(a)anthracene: protection by alpha naphthoflavone. AB - Bilateral or unilateral intraovarian injection with the polycyclic aromatic hydrocarbons 3-methylcholanthrene (3-MC), or 7,12-dimethylbenz(a)anthracene (DMBA) destroys oocytes in C57BL/6N and DBA/2N mice. The threshold for small oocyte destruction following bilateral intraovarian treatment with 3-MC was between 0.1 and 1 microgram/ovary in both DBA/2N amd C57BL/6N mice. After intraovarian treatment with DMBA, a more potent ovotoxin, the thresholds for small oocyte destruction were between 0.01 and 0.1 microgram/ovary. Calculated ED50's for small oocyte destruction following bilateral intraovarian treatment with 3-MC were C57BL/6N, 0.33 micrograms/ovary; DBA/2N, 1.02 micrograms/ovary- for DMBA the ED50's were C57BL/6N, 0.11 micrograms/ovary; DBA/2N, 0.03 micrograms/ovary. Unilateral intraovarian treatment also destroyed oocytes in the treated ovary. Treatment with intraperitoneal alpha-naphthoflavone (ANF), a competitive inhibitor of polycyclic aromatic hydrocarbon metabolism by microsomal monooxygenases, inhibited oocyte destruction. Intraovarian treatment with ANF decreased oocyte destruction produced by intraovarian DMBA. These data suggest that both 3-MC and DMBA are indirect acting ovotoxins requiring metabolic activation before oocyte destruction occurs. In addition, these data also suggest that the ovary contains the enzymes necessary to biotransform xenobiotics like 3 MC and DMBA to ovotoxic metabolites. Metabolic activation of xenobiotics to reactive products within the ovary may represent a special threat to the integrity of oocyte DNA. PMID- 2874632 TI - Progressive proliferative changes in the oviduct of mice following developmental exposure to diethylstilbestrol. AB - Structural malformation of the oviduct has been reported in experimental animal models and women following prenatal exposure to diethylstilbestrol (DES). To study histological changes in the oviduct in the absence of gross structural malformation, neonatal CD-1 mice were treated with DES (2 micrograms/pup/day) on days 1-5 of age. Focal epithelial hyperplasia was present at 1 month of age in 16 out of 18 (89%) of the DES-treated mice. At 4 months of age, general epithelial hyperplasia with multiple gland-like structures into and through the muscle wall of the oviduct was observed in 90% of the treated mice; by 12 months of age, epithelial hyperplasia and pseudogland formation were seen in 100% of the DES exposed animals. Epithelial hyperplasia and gland formation were not observed in control mice. The alteration induced by DES in the differentiation and proliferation of mouse oviductal epithelium suggests that the oviduct is a target for DES toxic effects. In addition, there was a progression of the epithelial changes with age. The histological changes described in this study may be partially responsible for the decreased fertility previously reported in this mouse model. Similar changes in the oviduct of DES-exposed women remain to be determined. PMID- 2874633 TI - Species differences in mutagenicity testing: I. Micronucleus and SCE tests in rats, mice, and Chinese hamsters with aflatoxin B1. AB - Three animal species used in in vivo mutagenicity testing--rats, mice and Chinese hamsters--were compared with respect to their mutagenic response to the mycotoxin aflatoxin B1 (AFB1). The micronucleus test and the SCE test with bone marrow cells were chosen as test methods, employing similar protocols for all species. The mutagenic potential of AFB1 was detected with rats and mice but not with Chinese hamsters. Rats were more susceptible to the mutagenic action of AFB1 than mice with regard to the effective dose. A difference in sensitivity between males and females was evident in rats and mice: male animals exhibited higher induced micronucleus frequencies than females, and a clear SCE-inducing effect was only detectable in male animals. These results are in agreement with those of in vitro and carcinogenicity studies. They may be due to metabolic differences between the species and sexes, predominantly differences in glutathione conjugation of the reactive AFB1 epoxide and in the formation of the metabolite aflatoxicol. Furthermore, it could be demonstrated that AFB1 seems to be a more potent inducer of micronuclei than of SCE. Since our results obtained with rats and mice were clearly positive, but with the Chinese hamster the mutagenic potential of AFB1 was not detectable with the test systems used, it can be concluded that the choice of an "inappropriate" test species may lead to a false negative judgment on the genotoxic potential of a test compound. PMID- 2874634 TI - An assessment of the effects of cyclophosphamide and sodium valproate on the viability of preimplantation mouse embryos using the fluorescein diacetate test. AB - The fluorescein diacetate test is a measure of both esterase enzyme activity and membrane integrity and it has been shown to be useful in assessing the viability of a variety of cells cultured in vitro, mouse embryos after freezing and thawing, and mouse embryos grown under inadequate culture conditions. In this study, the effects were examined of cyclophosphamide and sodium valproate administered respectively to pregnant inbred CBA mice 60 h after fertilization, on the viability of 84-h blastocysts. Cyclophosphamide 20 and 40 mg/kg bodyweight and sodium valproate 90 mg/kg significantly increased the number of nonviable blastocysts. Cyclophosphamide 4 mg/kg and sodium valproate 23 and 45 mg/kg did not adversely affect blastocyst viability. The intensity of embryo fluorescence correlated well with the subsequent development of the embryos in culture (r = 0.863; p less than 0.001). The test had a sensitivity of 83% and a specificity of 100%. Exposure of embryos to fluorescein diacetate under the conditions of this experiment did not adversely influence the subsequent postimplantation development of 84-h blastocysts cultured in vitro for a further 120 h. These findings suggest that the fluorescein diacetate test is a simple, rapid, and nontoxic procedure that may be useful in assessing the viability of preimplantation embryos after exposure to embryotoxic drugs and chemicals. PMID- 2874635 TI - Prenatal exposure to the fungicide dinocap causes behavioral torticollis, ballooning and cleft palate in mice, but not rats or hamsters. AB - The present study is an evaluation of the developmental toxicity of dinocap in three rodent species using an in vivo teratology screen. Our protocol uses postnatal viability, weight gain, and morphological and behavioral development through weaning to assess the developmental toxicity of compounds. Dinocap administered orally on days 7 to 16 of gestation to the CD-1 mouse resulted in increased postnatal mortality at 25 mg/kg/d (80% in block 1 and 40% in block 2). Many of the treated pups that died during the neonatal period were "ballooned" and had cleft palates. Although there was no treatment related mortality in the 12 mg/kg/d dosage group, 6% (14/226) of these mice and 24% (23/96) of the survivors from the 25 mg/kg/d dosage group displayed torticollis (a twisting of the neck resulting in an abnormal tilting of the head). These tilted-head mice held the head and forepart of the body tilted constantly to one side, both when resting and walking. The tilt was in either direction but was always constant for a given animal; in different mice, the angle varied considerably from almost 0 to 30 degrees. Some mice circled repeatedly in one direction in the home cage, others bobbed their heads and did back-flips, while others rolled over, always rolling in the same direction. In the hamster, developmental toxicity was seen at (100 and 200 mg/kg/d) or near (50 mg/kg/d) maternally toxic doses but no behavioral alterations were noted and none of the pups were ballooned. PMID- 2874636 TI - Effects on the fetal rat intestine of maternal malnutrition and exposure to nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether). AB - The effects of maternal protein-energy malnutrition and exposure to nitrofen on selected aspects of intestinal morphology and function were studied in the fetal rat. Pregnant rats were fed, throughout gestation, diets containing 24% or 6% casein as the sole source of protein. Reduced total food intake produced protein energy malnutrition (PEM). Each diet group was divided in half and gavaged with either 12.5 mg nitrofen in corn oil/kg/day or corn oil carrier only from days 7 to 21 of gestation. Body weight, intestinal weight, length, and diameter were measured as were villus length (VL), villus width (VW), and number of villi per length of intestine (VMM). Protein (horseradish peroxidase) and lipid absorption were studied histochemically. Lactase and dipeptidase activities were determined in proximal, medial, and distal thirds of the intestine. Results showed that the restricted maternal diet resulted in reduced fetal body weight (BW), intestinal weight (IW) and length (IL), reduced IW/BW and IW/IL ratios, VH, and VMM. The VW was reduced only in the distal third. Protein and lipid absorption were unaffected. Lactase and dipeptidase activities were reduced. Maternal nitrofen exposure resulted in reduced body weight, intestinal size, and lipid absorption, with some evidence of interaction with the diet effects on enzyme activities. It is concluded that effects of maternal malnutrition were extensive, but that nitrofen exposure, at this dosage level, is not likely to contribute to the postnatal fetal mortality rate in either adequately nourished or malnourished rats. PMID- 2874637 TI - An improved procedure for the efficient injection of radioactive steroids into mouse embryos. AB - Retention of 3H-moxestrol in mouse fetuses after transmaternal, intrafetal, and intraplacental injection were compared. Direct injection into the allantoic placenta resulted in greater retention of radioactivity by the fetus than the other modes of administration between 12 and 16 days of gestation. By this same criterion, intrafetal injection was best for older fetuses. Maternal injection was the least efficient way to transfer 3H-moxestrol to the fetus. PMID- 2874638 TI - Transplacental genetic and cytogenetic effects of alkylating agents in the mouse. II. Induction of chromosomal aberrations. AB - Six monofunctional alkylating agents, trenimon, cyclophosphamide, and isoniazid were proven for transplacental cytogenetic activity in mouse embryos at day 10 of gestational age under the same conditions as used in the mammalian spot test. With the exception of isoniazid, all compounds led to an increase in the aberration frequencies in embryonal cells. The results were statistically not significant in the case of EMS, while all other chemicals showed a dose-dependent clastogenic activity. After treatment with monofunctional alkylants, chromatid breaks were dominating, while polyfunctional compounds also produced chromatid exchanges, especially in the case of trenimon. ENU and DMS showed a very early aberration maximum 6 hr after injection. For both compounds, very similar dose response curves were found for induction of chromatid breaks in the dose range 10 75 mg/kg. There is no correlation between the Swain-Scott factors of monofunctional alkylants and their ability to induce chromosomal damage when compared in terms of pharmacological doses. A quantitative comparison of data found in the cytogenetic test in embryonal cells with those obtained in the mammalian spot test led to the conclusion that chromosomal mutations are of minor relevancy for the expression of recessive alleles in heterozygous mouse embryos. With this respect, the mammalian spot test must be considered as an in vivo test for the detection of gene mutations in somatic cells of the mouse. PMID- 2874639 TI - Induction of sister chromatid exchange in preimplantation mouse embryos in vitro by 3H-thymidine or ultraviolet light in combination with caffeine. AB - Preimplantation mouse embryos were exposed in vitro to 3H-thymidine (25, 100, or 250 Bq/ml) or ultraviolet (UV) light (1.35 or 4.05 J/m2), either alone or in combination with caffeine (1 mM with 3H-thymidine and 0.5 mM with UV light). Exposure to 3H-thymidine lasted for 2 days, from the two-cell stage to the late morula/early blastocyst stage, and UV radiation was applied acutely at the late morula/early blastocyst stage. The effects were quantified by the sister chromatid exchange (SCE) assay. All three agents induced SCEs when used singly. 3H-thymidine was effective in inducing SCEs only at 250 Bq/ml, whereas UV light was effective at both fluences. Although caffeine did not induce SCEs when it was added before exposure to bromodeoxyuridine (BrdUrd), which is used to visualize SCEs, it did induce SCEs when present during the entire culture period (3H thymidine experiments) or during incubation in BrdUrd (UV experiments). Caffeine markedly enhanced the SCE-inducing effect of UV light but did not influence the effect of 3H-thymidine. PMID- 2874640 TI - Maternal administration of cyclophosphamide induces chromosomal aberrations and inhibits cell number, histone synthesis, and DNA synthesis in preimplantation mouse embryos. AB - The effects of cyclophosphamide (CPA), administered to pregnant inbred CBA/Ca mice 60 h after copulation, on cell number, mitotic index, chromosome structure, histone synthesis, and DNA synthesis of 84-h blastocysts, and the subsequent development of these blastocysts cultured for a further 120 h in vitro are described. Cyclophosphamide 4, 20, and 40 mg/kg significantly increased the number of chromosomally aberrant cells, chromosomal aberrations, and chromosome breaks in the blastocysts. Chromosomal rearrangements were significantly increased in the CPA 20 and 40-mg/kg treated groups, and in the 40-mg/kg group the number of cells with ring chromosomes was significantly increased. Histone synthesis and DNA synthesis were significantly inhibited in the CPA 20 and 40 mg/kg treated groups. Blastocyst cell number in each of the treated groups was less than the controls. On subsequent culture in vitro, significantly fewer embryos in the CPA 20 and 40-mg/kg groups hatched, attached, developed trophoblast outgrowths, and expanded their inner cell masses. However, the differentiation of inner cell mass into ectoderm and endoderm was impaired by all three doses of the drug. These results demonstrate that CPA administered to pregnant mice 60 h after copulation has a clastogenic effect and interferes with synthesis of DNA and histones in the preimplantation embryo, and that the drug inhibits the subsequent development and differentiation of these embryos. Cytogenetic analysis of preimplantation embryos might be a useful adjunct to the existing methods in the evaluation of the embryotoxicity of drugs and chemicals. PMID- 2874641 TI - Co-culture of rat embryos and hepatocytes: in vitro detection of a proteratogen. AB - The technique of whole embryo culture developed by New [Environ Health Perspect 18:105-110, 1976] provides a sensitive assay to evaluate the effects of a test chemical on embryo development independent of maternal influences. To detect proteratogens, this assay must be coupled with an exogenous metabolic activation system. We have developed methods for the co-cultivation of rat embryos with primary hepatocytes, which offers several advantages over subcellular fractions when providing metabolic activation for in vitro assays. In the present study, rat embryos removed from the dam on day 10 of pregnancy were co-cultivated in vitro with primary cultures of rat, rabbit, or hamster hepatocytes. Embryos co cultivated with hepatocytes developed normally, as did embryos exposed to a test chemical, cyclophosphamide (CP) in the absence of hepatocytes. When embryos were co-cultivated with hepatocytes and exposed to CP, a dose-related embryotoxicity was observed, indicating metabolic activation of the proteratogen. Using hepatocytes isolated from rats pretreated in vivo with phenobarbital, we observed an increase in CP-induced malformations and embryotoxicity compared to those of embryos exposed to CP in the presence of uninduced hepatocytes. The teratogenic bioactivation of CP was inhibited in vitro by the addition of metyrapone. When similar numbers of hepatocytes were used for metabolic activation of CP the induced embryotoxicity was greater in the presence of rabbit and hamster hepatocytes than with rat hepatocytes. Development of procedures for the culture of rat embryos with hepatocytes from other species suggests the utility of this in vitro system for the investigation of species differences in sensitivity to chemical teratogens. PMID- 2874642 TI - Effect of prenatal propranolol exposure on development of the postnatal rat heart. AB - Maternal propranolol (PRO) treatment has previously been associated with adverse effects on the fetus and neonate. In the present study, pregnant rats were treated with PRO (25 or 50 mg/kg/day s.c.) on gestation days 8-20 to assess its possible effects on the developing heart. Maternal weight gain and pup weight on postnatal day (PND) 1 were reduced in a dose-dependent manner; litter size was unaffected. Pup body weight and heart weight both showed a dose-related decrease at all ages tested (PNDs 5/6, 8/9, 15/16, and 22/23). Since heart protein, but not DNA, was similarly reduced, the decrease seen in heart weight most likely reflects a decrease in cell size instead of cell number. Basal ornithine decarboxylase (ODC), an enzyme associated with growth and development, was unaffected by maternal PRO treatment. Insulin and isoproterenol stimulation of ODC, suggested markers for testing the function of the sympathetic pathway to the heart and of the heart's ODC response system, respectively, also showed no PRO related response. In conclusion, prenatal PRO exposure resulted in reduced body weight, heart weight, and heart protein, but had little effect on heart DNA or ODC activity. Since PRO treatment also reduced maternal weight gain, the adverse effects seen in the pups may be due to generalized PRO toxicity. The results suggest that when high PRO doses were used clinically, the careful monitoring of maternal weight gain during pregnancy might be useful in predicting adverse fetal effects. PMID- 2874643 TI - Cardiovascular defects in rat embryos cultured on serum from rats chronically exposed to phenytoin. AB - Headfold-stage rat embryos were cultured for 48 hours on serum from rats chronically exposed to phenytoin for periods as long as from conception until 11 months of age. Serum from phenytoin-exposed rats caused approximately 50% of the cultured rat embryos to develop cardiovascular defects as compared to 12% for controls. These morphological abnormalities included hemorrhaging of blood vessels within the embryo, pericardial edema, and absence of yolk sac circulation. Neither serum glucose nor phosphate levels nor serum osmolality were appreciably affected by phenytoin treatment. However, serum protein concentration was reduced in rats exposed to phenytoin as compared to controls. An absence of the serum protein hemopexin was associated with the reduction in serum protein levels but did not appear to be responsible for the observed cardiovascular defects. PMID- 2874644 TI - Induction of sister chromatid exchanges and chromosome damage by gossypol in bone marrow cells of mice. AB - The chromosome-damaging potential of gossypol was evaluated by scoring sister chromatid exchanges (SCEs), determining the percentage of pulverized metaphases and the mitotic index in bone marrow cells of mice. Bone marrow cells were collected approximately 21 hours after the intraperitoneal (0,20,40,80, or 160 micrograms/g) and oral (0,40,80, or 160 micrograms/g) administration of gossypol acetic acid. Irrespective of the dosing schedule (single or multiple doses), the vehicle used (physiological saline, corn oil, or 10% aqueous ethanol), and the route of administration, the mean SCE count per cell was significantly higher (P less than 0.05) in gossypol-treated groups than their control counterparts. At 80 and 160 micrograms/g dose levels, the occurrence of metaphase chromosome pulverization was significantly greater, while mitotic index values were markedly lower than those of the corresponding control values. The results suggest that gossypol is a potentially mutagenic and clastogenic agent in murine bone marrow cells. PMID- 2874645 TI - Suppression by cyclohexanetriones of retinoic acid-induced cartilage degradation in vitro and teratogenicity in vivo. AB - In cultured fetal rat bones, cyclohexanetriones that stimulate prostaglandin synthesis inhibited retinoic acid-induced cartilage degradation in a dose dependent manner. The inhibition by the cyclohexanetrione Ro 31-0521 was reversible, indicating that the effect was not due to cytotoxicity. Excess retinoic acid is teratogenic in rats and adversely affects the normal differentiation of various morphogenetic systems, depending on the time of administration. The following retinoic acid-induced malformations were suppressed by Ro 31-0521: malformations of long bones and of apical phalanges induced on days 13 and 15 of gestation, respectively; spina bifida and tail malformations induced on day 11 of gestation and cleft palate induced on day 15 of gestation. However, cleft palate and other head malformations including exencephaly induced by retinoic acid on day 11 of gestation were not suppressed but even increased by Ro 31-0521. At a high dose, Ro 31-0521 given alone on day 11 of gestation was embryolethal and teratogenic but was not on the tested other days, indicating that the cyclohexanetrione at specific stages and doses also interfered with normal morphogenesis like retinoic acid. Assuming that stimulation of prostaglandin synthesis is the main biological effect of the cyclohexanetriones, our findings suggest that prostaglandins may be involved in mediating retinoid action. PMID- 2874646 TI - The predictive value of enzymuria in cyclosporin A-induced renal toxicity in the rat. AB - The acute nephrotoxic properties of cyclosporin A (CsA) were investigated in normotensive, adult male Sprague-Dawley rats. Animals received either 50 or 100 mg CsA/kg by gastric intubation for 7 days. Within 24 h, significant increases in urinary N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma GT) activity were observed at both doses of CsA. Renal function abnormalities, however, were not apparent until 2 days (100 mg/kg) or 7 days (50 mg/kg). Progressive increases in enzymuria were evident in both groups between 1 and 4 days, at which later time proximal straight tubular cell damage was first observed. The data obtained using this model clearly demonstrate that enzymuria provides a sensitive index of acute CsA-induced renal cell damage and that enzymuria precedes detectable renal functional and structural abnormalities. PMID- 2874647 TI - Evaluation of toxic effects following administration of monoclonal antibody MBr1 in patients with breast cancer. AB - Twelve patients with disseminated breast cancer were injected with monoclonal antibody MBr1 at the National Cancer Institute of Milan, Italy, from January 1983 to March 1985. The first seven patients had advanced disease and the remaining five operable breast cancer. In the first seven patients the initial dosage of MBr1 was 0.5 mg and was doubled in the next patient up to 16 mg. The last five women received 10 mg of MBr1. No general side effects such as bronchospasm, hypotension, immediate or delayed allergic reactions were observed. Four patients who were injected with 10 mg or more experienced fever, shudder and vague abdominal and articular pain. The following tests were monitored: R.B.C., W.B.C., percentage of lymphocytes, blood glucose, urea nitrogen and creatinine, serum levels of Na+, K+, Cl-, total proteins levels, albumins and globulins, bilirubin, GOT, GPT, alkaline phosphatase, LDH, amylase, gamma GT and CPK. No major modifications were observed: a limited increase of the transaminases, LDH and gamma GT was evident at the last check. An early temporary alteration of CPK was observed in the four patients who had symptoms. Serum levels of MBr1 are detectable immediately after injection starting from 4 mg, and all sera were negative 48 hours later. It is concluded that the scanty toxicity allows to continue clinical investigations to verify the linkage between MBr1 and Ca-MBr1 "in vivo" after a single injection of no more than 16 mg of the MoAb. The increase of this dosage as well as multiple injections do not seem safe at present. PMID- 2874648 TI - [Animal experiment studies on improving ischemia tolerance of the testis]. AB - The reactions of the germinative testicular epithelium after definite ischemia periods were studied in rats. Using heparin the testicular ischemia tolerance has already been prolonged; this can be distinctly improved by adding alphareceptor blockers. The consequences of a 30 min and 2 h period of testicular ischemia are nearly eliminated by the described medicamentous combination. The experimental results show that at present the use of heparin and alpha-receptor blockers seems to be the best way, to extend the ischemia tolerance during autotransplantation of testicles. PMID- 2874649 TI - [Trials of immunostimulation of an antitoxic response with levamisole in the immunization of sheep with a combined clostridial vaccine]. AB - Comparative investigations were carried out on the antibody level in test animals -sheep, vaccinated with a polyvaccine against C and D enterotoxemia and necrotic hepatitis as well as in combined application with Levamisol. It was found that with the use of the preparation the stimulation of immunogenesis with type D and necrotic hepatitis--type B antigens (included in the composition of the polyvaccine) was enhanced. No stimulation of immunogenesis with the type C specific antigen was found within the period of investigation. Immunity was better built up when the animals were treated with the combined product as compared with the controls, given the polyvaccine without Levamisol. PMID- 2874650 TI - Calcitonin immunoreactive cells in prostate gland and cloacal derived tissues. AB - Calcitonin- and serotonin-storing cells have been immunocharacterized in prostate gland, urethra, urinary bladder and anal canal. In addition, a few hCG and somatostatin immunoreactive cells have been detected in prostate gland. All these cells were dispersed throughout the epithelial lining. In the anal canal, calcitonin cells were exclusively confined to the anal ducts and anal transitional zone epithelium. Calcitonin and serotonin cells were seen in some examples of prostatic adenocarcinoma. Combined techniques most often showed coexistence of calcitonin and serotonin immunoreactivities in the same endocrine cell. hCG immunoreactive cells corresponded to a subpopulation of serotonin-, calcitonin-storing cells. Calcitonin and serotonin cells were present in most organs which originated from the cloaca. In this territory, this distinctive endocrine pattern could be regarded as an excellent marker of cloacal derived tissues. These tissues constitute an additional site for extrathyroid C-cells. It is likely that calcitonin cells are a component of some prostatic adenocarcinomas. PMID- 2874651 TI - The induction of accelerated murine amyloid with human splenic extract. Probable role of amyloid enhancing factor. AB - Amyloid enhancing factor (AEF) is derived from the tissues of pre-amyloidotic and amyloidotic animals and, when transferred, greatly accelerates amyloid induction in the recipient murine models. It has also been reported that similarly accelerated amyloid induction can be achieved in mice by injection of human splenic homogenates from patients with amyloidosis. The present study has attempted to characterize further the mechanism of this "heterologous transfer of amyloid". Treatment of mice with the "tissue homogenate" or the "AEF extract" of AA-, AL- and A prealbumin-laden human spleens followed by daily subcutaneous casein injections induced amyloidosis in an accelerated fashion. The resultant amyloid deposits in mice had strongly positive immunohistochemical reactions with anti-mouse AA, and negative reaction with anti-human AA or anti-human prealbumin. The results lend support to the idea that accelerated amyloid induction in the recipient mice is unlikely to be due to transfer of human amyloid substance, but rather to formation of "native" murine amyloid under the influence of a human AEF factor similar to or identical with AEF described in mouse-to mouse transfer models. PMID- 2874652 TI - Superficial intimal injury of the rabbit carotid artery induced by distilled water. AB - The study of mechanical injury to the aortic endothelium in experimental animals is important in understanding the pathologic processes in atherogenesis. In this investigation distilled water was used to produced superficial injury to the rabbit carotid artery. Sterilized distilled water was injected into a temporarily isolated segment of rabbit carotid artery measuring 0.5 cm in length. After 4 min blood flow was reestablished by removal of the isolating ligatures. The carotid arteries were examined at time intervals of 5 min, 24 h, 48 h, 1 month, 3 months and 6 months after injury. Five min after injury, the carotid endothelial cells were almost completely removed but no medical injury was present. After 24 and 48 h, a few platelets were adherent to the denuded intimal surface. After 1 month, 3 months and 6 months the injured surface showed a slight intimal thickening consisting of modified smooth muscle cells. Our experimental findings suggested that the extent of the injured area is more important in the repair process than its depth. PMID- 2874653 TI - Fine structural aspects on the fate of rat black thyroids induced by minocycline. AB - The fate of the black thyroid induced by minocycline treatment (100 mg/kg daily for 21 days) in the rat was studied by light and electron microscopy after 6 months. The black discoloration of the thyroid gland remained and numerous dense bodies containing highly electron-dense deposits were seen in most of the follicular epithelial cells. It appears that the turnover rate of follicular epithelial cells is very low and the electron-dense deposits are largely retained, though debris derived from degenerate follicular epithelial cells containing the dense deposits may be phagocytosed by macrophage-like cells in the interfollicular connective tissue. Brown-black granules are also found in the extremely attenuated follicular epithelial cells of cold follicles. PMID- 2874654 TI - Ultrastructural and immunocytochemical aspects of lymphocytic submandibulitis in the non-obese diabetic (NOD) mouse. AB - The submandibular glands of female non-obese diabetic (NOD) mice (22-26 weeks of age) were studied by light and electron microscopy. Mononuclear cells consisting mostly of lymphocytes were recognized in and among the acini and secretory ducts. Some parts of the secretory ducts and mucous acini surrounded by lymphocytes showed destructive changes. In the secretory ducts lymphocytes invaded the duct epithelial lining and the duct lumen was occluded by these cells. The duct epithelial cells in such lesions were extremely distorted and tonofilament bundles running in various directions were present in the cytoplasm. Lymphocytes were in close contact with the duct epithelial cells. In the mucous acini some acinar cells, which appeared to be compressed by the infiltrating lymphocytes, showed degenerative changes. Immunocytochemical study revealed that both T- and B lymphocytes were involved, T-lymphocytes tending to occupy the center of the infiltrate, while B-lymphocytes occupied the periphery. Although autoantibody against duct epithelial cells was identified, damage to duct epithelial cells was not correlated with the presence of this antibody. The morphological changes in the submandibular gland of the NOD mouse are very similar to those reported in the salivary gland of patients with Sjogren's syndrome. PMID- 2874655 TI - Association of human hepatocellular membrane fusions with non-A, non-B hepatitis. AB - Liver biopsies from patients with alcoholic hepatitis, chemical hepatitis, or viral hepatitis types A, B, or non-A, non-B were examined by electron microscopy. Circular, fused, cytoplasmic membranes were observed in hepatocytes of 17% of patients with hepatitis type B and 92% of patients with hepatitis type non-A, non B. The membrane alterations were not observed in hepatocytes of patients with the other types of hepatitis. The greater frequency of altered cytoplasmic membranes in hepatocytes of patients with non-A, non-B hepatitis was shown to be statistically significant (p less than 0.05) when compared to that in patients with viral hepatitis type B. PMID- 2874656 TI - The suramin-treated rat as a model of mucopolysaccharidosis: reversibility of biochemical and morphological changes in the liver. AB - Rats treated with the trypanocidal drug suramin, a potent inhibitor of several lysosomal enzymes, develop a storage disorder which mimics the features of mucopolysaccharidosis (Constantopoulos et al. 1983). In this paper we have examined the reversibility of the biochemical and pathological changes induced in the liver of the suramin-treated rat. Rats were injected with a single intravenous dose of suramin (250 mg/kg) and allowed to survive for periods of up to 6 months. The liver was examined for suramin content, pathological changes, biochemical storage of glycosaminoglycans (GAGs) and for the blockade of the relevant hydrolytic enzymes. GAG storage in the liver peaked at approximately 14 days after administration of suramin when there was a five-fold increase in the GAG content. Thereafter GAGs decreased in parallel with the fall of suramin concentrations so that within 6 months the content had returned to control levels. The activity of most of the enzymes tested had also returned to control levels within 6 months. The pathological changes which are evident in the liver 1 2 weeks after administration of the drug had diminished considerably within 6 months. These results indicate that significant reversibility of both the biochemical and pathological changes induced by suramin occurs and they support the suitability of the suramin treated rat as a model to assess the value of therapeutic treatments of mucopolysaccharidosis. PMID- 2874658 TI - Flow cytometric DNA measurements in human thyroid tumors. AB - By means of flow cytometry (FCM), DNA distribution pattern and the fraction of cells in the various phases of the cell cycle were studied in 52 samples of normal thyroid tissues, follicular adenomas, follicular carcinomas, medullary carcinoma and fibrosarcomas. In the normal thyroid tissues and follicular adenomas DNA diploid cell populations only were found. Among 20 follicular carcinomas in 13 cases (65%) together with the DNA diploid cells, DNA aneuploid cell lines were also observed. S-phase fraction in follicular adenomas is higher than in the normal thyroid tissues and lower than those in thyroid carcinomas. The percentage of S-phase cells in DNA aneuploid populations is significantly higher (S = 19 +/- 9.3%) than in the diploid cell lines (S = 3.7 +/- 2.6%). DNA aneuploid cell populations were predominantly observed in carcinomas with a high degree of morphological anaplasia. PMID- 2874657 TI - Role of microglia in plaque formation in senile dementia of the Alzheimer type. An immunohistochemical study. AB - Using immunohistochemical and enzyme histochemical methods, we have investigated the presence of mononuclear phagocytic cells around senile plaques in six brains from patients with senile dementia of the Alzheimer type (SDAT). It is generally supposed that reactive microglial cells are involved in amyloid formation "as representatives of the reticuloendothelial system in the brain." We used different monoclonal antibodies directed against cells of the mononuclear phagocyte lineage, antibodies against the macrophage markers alpha 1 antichymotrypsin and lysozyme, and the lectin WGA, in addition to enzyme histochemical staining for nonspecific esterase and acid phosphatase. It was concluded that no macrophages of the mononuclear phagocyte lineage are involved in plaque formation. The role of glial cells in amyloid formation is discussed. PMID- 2874659 TI - Keratin polypeptide distribution in benign and malignant breast tumors: subdivision of ductal carcinomas using monoclonal antibodies. AB - Monoclonal antibodies which recognize one or only a few keratin polypeptides have been used to study the distribution of different keratins in benign and malignant breast lesions by immunocytochemical methods. Seven monoclonal antibodies which recognized either different keratin polypeptides by immunoblotting techniques, or identified different epithelial cell types in complex tissues were used. In two mastopathies and three fibroadenomas the antibody lu5 stained luminal cells as well as myoepithelial cells. In contrast the antibodies CK7, Troma 1, CK2 and KA4 labeled only luminal cells, whereas antibody CKB1 decorated only myoepithelial cells. All 15 ductal carcinomas showed a uniform staining of tumor cells with the antibodies Troma 1, CK2, KA4 and lu5. The antibody CK7 also stained all ductal carcinomas, but in two specimens the staining was heterogeneous. The antibody CKB1 decorated only the pre-existing myoepithelial cells in 11 of 12 ductal carcinomas but in the remaining specimen the tumor cells were also strongly positive. Tumor cells in lobular carcinomas were labeled by antibodies CK7, Troma 1, CK2, KA4, bu not by CKB1. The antibody CKS1 showed no staining of any of the benign and malignant breast lesions. PMID- 2874660 TI - [Organization of nutrition for persons subjected to long-term hyperbaria (review of the literature)]. PMID- 2874661 TI - Correlation of immune defects in hemophilia with HTLV-III antibody titers. AB - Of 170 hemophilia patients, 22% had high-titer, 29% had low-titer, and 49% had no antibodies against HTLV-III. The strength of HTLV-III antibodies was correlated significantly with a decreased OKT4/T8 ratio (p less than 0.0005), decreased in vitro response to pokeweed mitogen (p less than 0.025), and elevated serum neopterin (p less than 0.05) and serum IgG (p less than 0.0005). The fraction of patients with abnormal immunological findings was consistently greater among patients with high-titer than among patients with low-titer HTLV-III antibodies. Testing these immunological parameters may be useful for monitoring the breakdown of immune functions leading to AIDS. PMID- 2874662 TI - Red cell antigens P (globoside) and Luke: identification by monoclonal antibodies defining the murine stage-specific embryonic antigens -3 and -4 (SSEA-3 and SSEA 4). AB - Two globoseries antigens (antigens borne on carbohydrate chains containing globoside), SSEA-3 and SSEA-4, were found on the red cells of the majority of people, but were absent from cells of rare p and Pk individuals which lack globoside. In addition, SSEA-4 was absent from red cells of Luke(-) individuals which nevertheless express the P antigen (globoside) and SSEA-3. The name LKE is proposed for the red cell antigen detected by the Luke serum and by MC813-70, the monoclonal antibody defining SSEA-4. Among the LKE+ individuals, a few showed relatively weak expression of the antigen and were grouped separately as a LKE weak (LKEw) phenotype. Using MC813-70, the frequencies of the 3 phenotypes LKE+, LKEw and LKE- in an English donor population are 0.914, 0.072 and 0.014, respectively. PMID- 2874663 TI - [Beta blockade with celiprolol in tardive dyskinesia patients treated with neuroleptics]. AB - The influence of celiprolol on the symptoms of tardive dyskinesia was compared with placebo in a randomized double blind study. 17 female patients were treated with a single daily dose of 200 mg celiprolol and 18 female patients received placebo for a period of 3 months. All patients got additional neuroleptic treatment. Celiprolol produced a small decrease in heart rate and systolic blood pressure, but had no influence on the diastolic blood pressure. The effects of celiprolol on the symptoms of tardive dyskinesia were similar to those of the placebo; in both groups improvements and deteriorations were observed. One patient of the celiprolol group became symptom free. Two cases of collapse occurred after 10 weeks of treatment with celiprolol. In one case collapse was associated with diarrhoea, in the other case the patient had preexisting hypotensive circulatory dysregulation. Sporadic reports about the effect of propranolol in patients with tardive dyskinesia might reflect the normal progress of the disease or the effect might depend on the different pharmacological profile of propranolol. PMID- 2874664 TI - Long day's journey into night: women and prescription drug abuse. AB - Standard explanatory models of addiction are reviewed, including personality theory, locus of control, behaviorist theory, social learning, biochemical and socioeconomic theories, in the context of understanding the female preponderance in prescription drug addiction. Alexander and Hadaway's "adaptive" model of addiction is presented as a more comprehensive model of female prescription drug addiction, encompassing relevant and therapeutically useful aspects of earlier models. It also permits both the individualization of the model to each woman's particular situation, and also the incorporation of common themes stemming from sex-role stereotyping, low status in the society, and the power dynamic of the male physician-female patient interaction. PMID- 2874665 TI - Debrisoquine polymorphism and the metabolism and action of metoprolol, timolol, propranolol and atenolol. AB - The contribution of debrisoquine polymorphism to the metabolism and action of beta-adrenoceptor antagonists (beta-blockers) varies widely between drugs. Oxidation phenotype is a major determinant of the metabolism, pharmacokinetics and some of the pharmacological actions of metoprolol, bufuralol and timolol. The poor metabolizer phenotype is associated with an increased area under the plasma drug concentration vs. time curve, a prolongation of elimination half-life and a more intense and sustained beta-blockade. The stereoselective metabolism of metoprolol also displays phenotypic differences, which should be taken into account when interpreting plasma concentration vs. response relationships. Studies in vivo and in vitro have identified some of the metabolic pathways which are subject to this defect, namely the alpha-hydroxylation and the O demethylation of metoprolol and the 1'-hydroxylation of bufuralol. In contrast, the pharmacokinetics and pharmacodynamics of propranolol, which is also extensively oxidized, are not related to debrisoquine polymorphism, although 4' hydroxypropranolol formation is deficient in the poor metabolizer phenotype. The disposition of atenolol, which is almost completely eliminated unchanged by renal and faecal excretion, is independent of oxidation phenotype. If standard doses of some beta-blockers are used in poor metabolizers, these patients may be susceptible to concentration-related adverse reactions and they may also require lower and less frequent dosing for control of angina pectoris. PMID- 2874667 TI - [Therapy with beta-blockers in acute myocardial infarction in the aged]. AB - Starting from the fact that during the first days the mortality is essentially determined by the degree of severity of the infarction and its complications, a particularly critical evaluation of the results is required. Patients with a bad prognosis usually have contra-indications for the application of beta-blockers during that phase. After the early complications have been overcome, the obtained findings are much easier to interpret in the sense of a therapeutical conception, and they have caused us to make the generalization--observing the contra indications--to use beta-blockers in the framework of a complex therapy of myocardial infarction wherever it is possible. The results obtained require further verification, but justify, however, optimism on their part. PMID- 2874666 TI - The molecular mechanisms of two common polymorphisms of drug oxidation--evidence for functional changes in cytochrome P-450 isozymes catalysing bufuralol and mephenytoin oxidation. AB - Using the stereospecific metabolism of (+)- and (-)-bufuralol and (+)- and (-) metoprolol as model reactions, we have characterized the enzymic deficiency of the debrisoquine/sparteine-type polymorphism by comparing kinetic data of subjects in vivo with their microsomal activities in vitro and with reconstituted activities of cytochrome P-450 isozymes purified from human liver. The metabolism of bufuralol in liver microsomes of in vivo phenotyped 'poor metabolizers' of debrisoquine and/or sparteine is characterized by a marked increase in Km, a decrease in Vmax and a virtual loss of the stereoselectivity of the reaction. These parameters apparently allow the 'phenotyping' of microsomes in vitro. A structural model of the active site of a cytochrome P-450 for stereospecific metabolism of bufuralol and other polymorphically metabolized substrates was constructed. Two cytochrome P-450 isozymes, P-450 buf I and P-450 buf II, both with MW 50,000 Da, were purified from human liver on the basis of their ability to metabolize bufuralol to 1'-hydroxy-bufuralol. However, P-450 buf I metabolized bufuralol in a highly stereoselective fashion ((-)/(+) ratio 0.16) as compared to P-450 buf II (ratio 0.99) and had a markedly lower Km for bufuralol. Moreover, bufuralol 1'-hydroxylation by P-450 buf I was uniquely characterized by its extreme sensitivity to inhibition by quinidine. Antibodies against P-450 buf I and P-450 buf II inhibited bufuralol metabolism in microsomes and with the reconstituted enzymes. Immunochemical studies with these antibodies with microsomes and translations in vitro of RNA from livers of extensive and poor metabolizers showed no evidence for a decrease in the recognized protein or its mRNA. Because the antibodies do not discriminate between P-450 buf I and P-450 buf II, both a decreased content of P-450 buf I or its functional alteration could explain the polymorphic metabolism in microsomes. The genetically defective stereospecific metabolism of mephenytoin was determined in liver microsomes of extensive and poor metabolizers of mephenytoin phenotyped in vivo. Microsomes of poor metabolizers were characterized by an increased Km and a decreased Vmax for S-mephenytoin hydroxylation as compared to extensive metabolizers and a loss of stereospecificity for the hydroxylation of S-versus R-mephenytoin. A cytochrome P 450 with high activity for mephenytoin 4-hydroxylation was purified from human liver. Immunochemical studies with inhibitory antibodies against this isozyme suggest the presence in poor-metabolizer microsomes of a functionally altered enzyme. PMID- 2874669 TI - [Experiments with Benham's disk]. PMID- 2874668 TI - [Acute effect of the cardioselective beta-1-partial agonist, Corwin, on ventricular function and myocardial oxygen consumption in patients with dilated cardiomyopathy]. AB - The effects on left ventricular function and myocardial metabolism of Corwin (ICI 118,587), a selective beta-1 partial agonist, were evaluated in 12 patients with dilated cardiomyopathy. All patients were in sinus rhythm at the time of cardiac catheterization. Immediately before and 20 minutes after intravenous administration of 0.2 mg/kg Corwin over 2 minutes, high-fidelity left ventricular pressures and thermodilution coronary sinus blood flow were recorded along with ventriculograms in the 30 degrees right anterior oblique projection. In 11 patients, Corwin resulted in no change in heart rate, a fall in left ventricular end-diastolic pressure, a rise in left ventricular systolic pressure and an increase in cardiac index. There was a rise in both peak positive and peak negative dP/dt. End-diastolic and end-systolic volume indices fell, and ejection fraction rose. There was an increase in coronary sinus blood flow and a small rise in myocardial oxygen consumption. In contrast to these results in the group as a whole, in one patient Corwin produced depression of both systolic and diastolic left ventricular function. We conclude that, in many patients with dilated cardiomyopathy, Corwin produces an improvement in systolic and diastolic left ventricular function while at the same time only slightly increasing myocardial oxygen demand. In some patients, however, Corwin may result in a significant worsening of left ventricular performance due to its antagonistic effects. PMID- 2874670 TI - Effects of graduated processing difficulty on P 300 component of the event related brain potential. PMID- 2874671 TI - [Multivariate analyses of relations between psychological parameters and changes in cerebral electric arousal activity within the scope of visual search processes]. PMID- 2874673 TI - Some enteropathogenic strains of Escherichia coli produce haemagglutinins associated with HEp2 epithelial cell adhesion. AB - Sixteen of 17 strains of Escherichia coli of traditional infantile enteropathogenic (EPEC) serotypes produced mannose-sensitive haemagglutinin (and type-1 fimbriae) after serial growth in nutrient broth. Two strains also produced mannose-resistant haemagglutinins (MRHAs) after serial growth in phosphate buffered broth but not in nutrient broth or after growth on phosphate-buffered agar. Some of the type-1 fimbriate EPEC strains adhered modestly in a mannose sensitive manner to HEp2 epithelial cells in a 30-min in vitro assay; two MRHA+ EPEC strains adhered well in a mannose-resistant manner. PMID- 2874672 TI - Characterization of Escherichia coli wild-type strains by means of agglutination with antisera raised against cloned P-, S-, and MS-fimbriae antigens, hemagglutination, serotyping and hemolysin production. AB - E. coli strains isolated from patients with urinary tract infections (UTI) very often possess mannose-sensitive (MS) and mannose-resistant (MR) adherence factors (fimbriae). According to their receptor specificity the mannose-resistant adhesins can be divided into several types, P, S, M and X. We have cloned the determinants of three groups of UTI E. coli adhesins, MS, P and S, and prepared specific antisera against the fimbriae antigens. 189 hemagglutination (HA+) positive strains, 96 fecal isolates and 93 strains isolated from UTI have been tested with these specific antisera and further characterized by receptor specific HA, HA patterns and further of the "common O serogroups" 01, 02, 04, 06, 07, 08, 018, 025, 075, most prevalent in UTI, and hemolysin production. 68 (73%) of the UTI strains and 50 (52%) of the fecal isolates showed P-receptor specificity; 16 (17%) of the uropathogenic bacteria and 33 (34%) of the fecal strains exhibited S, M or X-fimbriae antigens. 24% of the P-hemagglutinating (P+) strains reacted with P (F8)-specific antiserum. In contrast, more than three quarter of the S+-strains were agglutinated by S-specific antiserum. HA-pattern VI and 018 antigen were found to be associated with P-fimbriae strains, whereas HA-pattern V and VII and the O antigens 02 (M-type), 06 and 018 (S-type) occurred most frequently in P--strains. A high percentage of P-fimbriated strains showed mannose-sensitive hemagglutination and hemolysin production. PMID- 2874674 TI - Blood levels of somatostatin, pancreatic polypeptide and gastrin in normal cows and in cows suffering from abomasal dilatation. PMID- 2874675 TI - [gamma-GT activity in cow's milk during an udder function cycle in relation to processes in the mammary gland tissue]. PMID- 2874676 TI - [Activity of gamma-glutamyltransferase in the cerebrospinal fluid in various forms of cerebral arachnoiditis]. AB - Measurement of activity of gamma-glutamyl transferase (GGTF) in the cerebrospinal fluid (CSF) revealed a sharp elevation in the cytosis and activity of GGTF in the ventricular portion of the CSF, which points to dystrophic changes in nerve cells and damage of their membranes and, consequently, to an increase in the permeability of the blood-brain barrier. Determination of GGTF activity in the CSF may be recommended as a supplemental method of the differential diagnosis of cerebral meningites. PMID- 2874677 TI - [Efficacy of treating patients with vegetative and vascular crises of a neurotic nature (comparative electrophysiologic study)]. AB - On the basis of clinical, electrophysiological, psychologic and vegetative parameters, the authors treated 66 patients with vegetovascular crises of neurotic nature using acupuncture, beta-adrenoblockers, psychotropic means and a combination of beta-adrenoblockers with psychotropic drugs. Acupuncture led to changes in all the aforegoing parameters. Psychotropic therapy reduced activating influences, predominantly in the "ascending" direction, anaprilin led to the maximum inhibition of the vegetative component of the crisis. With all methods of treatment emotional-personality alterations showed the greatest degree of normalization. This confirms the correctness of the term "psycho-vegetative" syndrome which emphasizes the leading role of mental disorders in the genesis of vegetovascular dystonia in neurotic patients. PMID- 2874678 TI - [The place of atropine coma therapy in the complex treatment of hypochondriacal schizophrenia (non-delusional hypochondriasis)]. AB - In order to expand the possibilities of the treatment of resistant hypochondriac schizophrenia, the author developed a new method of multiple modality therapy which is based on the use of the rebound effectiveness of atropine comas. It consists of a course of atropine comatose therapy and a subsequent intensive medicamentous therapy in the form of intravenous instillation of psychotropic agents. This treatment was given to 36 patients with slowly progressive hypochondriac schizophrenia, whose clinical manifestations were restricted to a picture of non-delirious hypochondria. In most cases (82%) the treatment yielded a positive effect. The method was the most effective in patients with syndromes of obsessive and hysterical hypochondria as well as in those with cenesthopathic conditions. The use of therapy in rigid hypochondria proved poorly effective. PMID- 2874679 TI - [The effects of taxol on the microtubule assembly in cultured human fibroblast cells]. PMID- 2874680 TI - Interference with thyrotropin receptor antibody determination by a spuriously occurring anti-bovine TSH antibody. AB - Abnormally negative values of thyrotropin binding inhibitor immunoglobulin (TBII) were found in the sera from a patient with Graves' disease. This was due to the presence of potent bovine TSH (bTSH) binding activity in the sera. This activity was demonstrated to be in immunoglobulin G (IgG) with a lambda light chain isotype, which was shown to have an affinity for bTSH with a Ka value of 3.5 X 10(10) M-1 and a maximum binding capacity of 1.1 X 10(-14) M/mg IgG. F(ab')2 fragments obtained through pepsin digestion from the patient's IgG retained bTSH binding activity. [125I] bTSH binding to this IgG was inhibited by the TSH receptor. The inhibition was not completely competitive, suggesting the presence of different binding sites for this IgG and the TSH receptor on the TSH molecule. This IgG, however, could not bind labelled human TSH (hTSH). Since neither TSH nor other pituitary derivatives had ever been given to the patient, this bTSH binding activity was considered to be due to a spuriously occurring anti-bTSH antibody. PMID- 2874681 TI - [From the target to the origin. Apropos of the treatment of Zollinger-Ellison syndrome]. PMID- 2874682 TI - Enzyme patterns in human endocytotic multinucleate giant cells--a histochemical study. AB - A series of human multinucleate giant cells (MGCs) of the endocytotic type were studied using enzyme histochemical methods for dehydrogenases, glycosidases, phosphatases, and peptidases. Several enzyme patterns were found. The subgroup of MGCs associated with inflammatory granulomatous processes (sarcoidosis, granulomatous myositis, familial granulomatosis, lymphogranuloma, granulomatous cholangitis) was characterized by high activities of nonspecific esterase (NE) and tartrate-sensitive acid phosphatase (AcPase-Ts). There was no detectable activity of peptidases or tartrate-resistant isoenzyme of acid phosphatase (AcPase-Tr). This enzyme equipment was indistinguishable from that in mononuclear precursors in the granulomas. The other MGCs of the series displayed enzyme patterns substantially different from their monocytic precursors (blood monocytes and Langerhans cells). The subgroup of foreign body associated MGCs (resorption of fat, keratin, and suture material) was characterized by high activities of NE, AcPase-Tr, and greatly variable activities of both peptidases studied. The latter lacked predilection for certain subcellular regions. The subgroup of osteoclasts and so-called giant cell tumours (osteoclastoma, giant cell tumour of soft parts, giant cell epulis of peripheral, and central types) displayed very low activity of NE, high activity of AcPase-Tr, and strong activities of peptidases. The latter were localized near the surface membrane of the polykarya. MGCs in histiocytosis X (HX) differed from the previous group by higher values of NE in average. All MGC types had common denominator in the absence of alkaline phosphatase activity, on average intense dehydrogenase activities, mostly low beta-glucuronidase and highly variable alpha-mannosidase activities. The enzyme pattern heterogeneity is discussed with regard to the phenomenon of enzyme induction and depression occurring in course of polykaryon production. The variability of phenomenon may reflect reactive adaptation to varying functional demands imposed on MGCs under different conditions. PMID- 2874683 TI - [Enzyme histochemical demonstration of sodium-dependent glutamate uptake in glutamatergic brain structures in the rat]. AB - Using a special tetrazolium salt technique, a striking correlation was observed between Na+ concentration of the incubation medium and the activity of glutamate dehydrogenase (GDH) in glutamatergic neuropil areas of the hippocampal formation, cerebellum, and other brain regions. Na+ concentration of 130 to 150 mmol/l caused maximal formazan production. The histochemical enzyme reaction in neuronal perikarya as well as biochemically estimated GDH activity were found to be rather inhibited by such Na+ concentrations. The GDH catalyzed sodium dependent increase in formazan production is discussed to be a consequence of the sodium dependence of glutamate uptake in glutamatergic brain structures supplying the enzyme with substrate. PMID- 2874684 TI - Argyrophil and argentaffin APUD cells in the human female prostate homologue and urethra. AB - In the female prostate homologue and urethra, numerous argyrophil and rare argentaffin cells were found. Grimelius method displayed the closed and open types of argyrophil cells in all cases this study. The findings indicate the possibility of endo/para/crine activity of the female prostate homologue and urethra and support the opinion on the non-vestigial role of the prostate homologue in woman. PMID- 2874685 TI - Topographical distribution of inflammatory leukocyte subsets in acute cellular rejection of a kidney allograft. AB - The topographical distribution of different mononuclear inflammatory cell subsets in acute cellular rejection of human renal allograft was analyzed. Marker antibodies to T cells (OKT11), T helper cells (T4), T suppressor/killer cells (OKT8), B cells (B-1), monocytes (OKM1) and mononuclear phagocytes at different stages (FMC17, FMC33) and the indirect immunoperoxidase method were employed. At early stages of rejection, T lymphocytes were mostly confined to the perivascular areas and there was a T helper (Th) cell predominance over T suppressor/killer (Tsk) cells in the inflammatory infiltrate. Very few T cells and monocytes were found to infiltrate the arterial wall. Mononuclear phagocytes dominated over T lymphoid cells in the intertubular areas. Later during rejection, the Th/Tsk ratio became inverted, inflammatory T cells invaded also the intertubular areas, and infiltration of the arterial wall by T cells and mononuclear phagocytes became evident. Granulocytes were associated with the late events in the graft, and their appearance coincided with beginning necrosis. These non-random features in the distribution of the inflammatory cells were most pronounced during early stages of acute cellular rejection; later on, the differences seemed to disappear. PMID- 2874686 TI - [Relationship between the central stimulation of atropine and cholinergic system]. PMID- 2874687 TI - [Anti-arrhythmic action of puerarin]. PMID- 2874688 TI - Effects of 1,1,1-trichloroethane on the cGMP metabolism in mouse brain. AB - Administration of 1,1,1-trichloroethane (TCE) to mice by inhalation or intraperitoneally reduced the cGMP contents of the brain stem, cerebral cortex, and vermis anterior, including the hemispheres. Following intraperitoneal administration the cGMP contents of the vermis posterior and hippocampus were also reduced. To investigate the mechanism underlying these changes, the effects of TCE on brain guanylate cyclase (GC) and phosphodiesterase (PDE) activities were examined after intraperitoneal administration in mice. The basal GC activities in the particulate and soluble fractions of the homogenates of the cerebellum, brain stem and cerebral cortex were not altered by TCE. In the cerebellum TCE treatment inhibited sodium azide-stimulated GC activity in the particulate and soluble fractions, while in the brain stem it enhanced the particulate GC activity induced by Ca2+. TCE treatment increased the rate of cGMP hydrolysis in the cerebral cortex and this was further accelerated by addition of Ca2+. Ca2+ also increased the rate of cGMP hydrolysis in the brain stem. However, in the cerebellum TCE enhanced the Ca2+-independent PDE activity as well as the enzyme activity in the presence of Ca2+ and exogenous calmodulin. These results indicate that the reduction of the cGMP content in the brain stem and cerebral cortex in vivo on exposure to TCE is due to changes in the rate of cGMP hydrolysis. In the cerebellum the TCE reduced cGMP content may be regulated by increased rate of cGMP hydrolysis as well as effects on the guanylate cyclase. PMID- 2874689 TI - Diagnostic potential of urinary enzymes and beta 2-microglobulin in acute urinary tract infection. AB - Urinary excretions of beta 2-microglobulin (beta 2M), N-acetyl-beta-D glucosaminidase (NAG), alanine aminopeptidase, beta-glucuronidase, acid and neutral alpha-glucosidase as indicators of proximal tubular dysfunction were measured in patients with acute upper and lower urinary tract infection (UTI) and fever of non-renal origin. The sensitivity of beta 2M was 67% and of NAG 49% as assessed in more than 100 episodes of acute pyelonephritis. Combined use of beta 2M and NAG increased the sensitivity to 75%. The degree of beta 2 microglobulinuria and enzymuria was comparable in patients with acute pyelonephritis and fever due to non-renal infections. The excretion of beta 2M and the various enzymes was too variable and unpredictable in individual cases to be useful as diagnostic indicator. In localizing an acute UTI, tests for proximal tubular dysfunction seem to be of no more clinical value than properly measured body temperature. PMID- 2874690 TI - Nervous system control mechanisms in heart failure. AB - Alterations in the peripheral circulation by influencing aortic impedance and venous capacitance have a remarkable effect on cardiac performance in patients with left ventricular dysfunction. Systemic vasoconstriction in heart failure is influenced by activation of the sympathetic nervous system (increased plasma norepinephrine), the renin-angiotensin system (increased PRA) and the antidiuretic hormone system (increased arginine vasopressin). The level of plasma norepinephrine is related weakly to the severity of resting left ventricular dysfunction and strongly to the subsequent risk of mortality. Attenuation of reflex responsiveness to low pressure mechanoreceptors (orthostatic tilt) and to carotid and aortic baroreceptors (nitroprusside infusion) occurs in heart failure and the degree of abnormality also may be related to mortality. Vasodilation with consequent improvement in left ventricular function may be accomplished by non specific dilators (nitroprusside, nitrates, hydralazine, nitrendipine) or by specific interference with neurohumoral mechanisms (sympathetic blockade, converting enzyme blockade, AVP blockade). Plasma norepinephrine may be reduced by central or presynaptic mechanisms (guanabenz, bromocriptine, captopril). The hemodynamic effect of this anti-sympathetic effect appears to be related to the relative influence on cardiac vs. peripheral sympathetic tone and/or concomitant effects of the drugs. Long-term trials are needed to determine whether chronic inhibition of the sympathetic nervous system will have a salutary effect on the hemodynamics, symptomatology and prognosis of cardiac failure. PMID- 2874691 TI - Adrenergic mechanisms in congestive heart failure. AB - The normal control of cardiovascular function exerted by the sympathetic nervous system is disturbed in congestive heart failure. The failing pump function of the heart evokes an increase in sympathetic activity which may be reflected in increased levels of plasma noradrenaline. However, these levels are generally below the concentrations needed to activate the adrenergic effector systems, indicating that the cardiovascular consequences of the increased sympathetic activity is not mediated by circulating noradrenaline. In the failing human heart there is a decrease in beta-adrenoceptor density which is related to decreasing ventricular function. This finding suggests that the myocardium is exposed to high concentrations of noradrenaline, inducing downregulation of the receptor number, despite the fact that in the failing heart the noradrenaline stores are reduced. In heart failure the plasma noradrenaline concentration was found to be directly related to mortality and was suggested to provide a better guide to prognosis than other commonly measured indexes of cardiac performance. PMID- 2874693 TI - Studies on endogenous ligands (endacoids) for the benzodiazepine/beta carboline binding sites. PMID- 2874692 TI - Some new positive inotropic agents. AB - In the search for new effective positive inotropic agents for the treatment of congestive heart failure (CHF), interest has focused mainly on two groups of agents namely adrenoceptor agonists and drugs inhibiting phosphodiesterase. Common for drugs belonging to both groups is that their positive inotropic effects seem to involve an increase in the intracellular concentration of cyclic AMP. Drugs acting by stimulation of beta 1- and/or beta 2-adrenoceptors (e.g. dopamine, dobutamine, prenalterol, pirbuterol, salbutamol, terbutaline, fenoterol) have initial beneficial effects, but seem to be ineffective for long term treatment. This has been suggested to be due to desensitization of the beta adrenoceptors, and means, if this effect can be definitely established, that beta adrenoceptor stimulation should be restricted to the acute treatment of CHF. Among drugs inhibiting phosphodiesterase, sulmazole, amrinone, milrinone, and fenoximone all have been shown to improve cardiac performance in patients with CHF during short-term treatment. However, results of long-term treatment with most of these drugs seem less encouraging. It has been suggested that these drugs may not be an effective approach to treatment of patients with CHF, since even if it is possible to achieve short-term gains, the long-term effects on the myocardium may be detrimental. Their ultimate place in the treatment of CHF remains to be established. PMID- 2874694 TI - Anxiety: its generation by drugs and by their withdrawal. PMID- 2874695 TI - Benzodiazepine, beta-carboline, and barbiturate actions on GABA responses. PMID- 2874696 TI - Bidirectional modulation of GABA function by beta-carbolines. PMID- 2874697 TI - Anxiolytic and anxiogenic beta-carbolines: tools for the study of anxiety mechanisms. PMID- 2874698 TI - [Intramedullary nailing as an alternate method in the management of slow-healing or pseudarthrotic upper and lower leg fractures]. AB - Intramedullary nailing of delayed healing fractures and non-unions in the lower extremity is the method of choice in biological and biomechanical aspects. With the technic of interlocking screws the indication is extended to the metaphyseal areas of tibia and femur. By nailing as alternative method an ossification of fractures and non-unions can be reached at a rate of about 90 per cent. This result is rather unique in the literature. In the treatment of shaft non-unions after cast fixation or rigid stabilisation by plates or external fixation nailing must succeed throughout its weight-bearing system and only fails in the case of infection and wrong indication. PMID- 2874699 TI - [Long-term results after conservative and surgical treatment of fractures of the distal end of the tibia]. AB - This is a clinical and radiological follow-up on 78 patients with 84 Pilon tibial fractures which were treated in our hospital between 1970-82. The fractures were arranged in three types after the classification of Ruedi, Matter, Allgower. 49 conservatively treated fractures were compared with 35 cases operated upon. The radiological follow-up focussed on posttraumatic development of arthrosis, the mobility of the ankle as well as on the posttraumatic result of reduction. The patient's own assessment concerning the result was found out by means of a questionnaire. The comparison of the fracture type I and II showed almost the same development of arthrosis after conservative and operative treatment, but the operated fractures of type III resulted in 33% in heavy arthrosis, whereas the cases treated conservatively showed heavy arthrosis in 50%. A close correlation exists between the quality of operative reduction and the development of arthrosis. A postoperative incongruity of the articular surface is followed by heavier arthrosis than a comparable incongruity after conservative treatment. An indication of an open reduction is given only if anatomical reconstruction can be predicted. PMID- 2874700 TI - [Functional treatment of fractures with the Neofract brace]. AB - Conservative treatment of a fracture is governed by generally accepted principles, in the first place absolute rest in the fractured region by inactivating the injured limb and adjacent joints. Hence, delayed healing of a fracture and formation of pseudarthroses are attributed to shear forces, insufficient retention and generally to lack of rest in the fractured area. On the other hand, the nonsurgical functional fracture treatment developed by Sarmiento in Los Angeles, U.S.A., considers unrest in the fractured area as an essential stimulant to osteogenesis of the fractured limb. This led to a new type of fracture treatment which largely does away with placing the limb at rest; on the contrary, the injured extremity may be subjected to stress quite early in fact, permitting minor movements in the fractured area and even aiming at such movements. The authors treated 32 fractures of the lower leg in this manner. Compared with fracture treatment of the conventional kind, such as via Kuntscher nailing, osseous consolidation - as measured by the time the patient was able to resume his work - occurred more rapidly. There was an absence of other features such as muscular atrophy and limitation of movement; if at all present, they were only slight. PMID- 2874701 TI - [Operative repositioning and retention of persistent scaphoid-lunate dissociation]. PMID- 2874702 TI - [Significance of early meniscectomy in the etiology of severe arthritis of the knee]. AB - With reference to 3579 meniscectomies performed in our clinic during 18 years as well as to cases with severe knee damage treated by arthroplasty, arthrodesis or correction osteotomy and their aetiopathological analysis with regard to previously performed meniscectomies, the following conclusions are drawn: Earlier meniscectomies seem to occur relatively often (up to 20%) in clinical cases of severe destructive processes in the knee e.g. knee arthritis. With reference to 3579 meniscectomies performed in this period this number is very low (1.34%) and under statistical aspects - therefore not essentially important. The analysis of the cases of our clinic operated on by means of plastics, arthrodesis or correction osteotomies showed, that an earlier meniscectomy was performed because of static axis faults. These axis deviations were the main reason not only for the meniscopathy but also for the further development of knee arthritis. Cases of severe knee arthritis, who could be referred to an earlier meniscectomy (traumatic lesion) without any deviation of the leg axis were very rare. The rarity of the development of a knee arthritis after meniscectomy seems to prove that evidently there is no disadvantage of the mainly performed total meniscectomy compared to the subtotal procedure. PMID- 2874703 TI - [Late results after meniscectomy]. AB - Lesion of the meniscus is the most frequently occurring lesion in the region of the knee joint. Opinions are still divided as to the effects of partial, subtotal or total meniscectomy in provoking and/or promoting arthrosis. In this study, 70 patients with isolated injury of the meniscus were followed up on an average 11 years after meniscectomy. The subjective and clinical findings are juxtaposed with the x-ray findings. It was found that no arthrosis or no increase of the already preoperatively existing degree of arthrosis was seen in only 21.4% of the patients. Correlations are set up between instability resulting from meniscectomy on the one hand, and degree of arthrosis on the other. PMID- 2874704 TI - [Importance of traction-wiring osteosynthesis as dynamic stabilization after acromioclavicular joint dislocation. A critical view]. AB - Various operating procedures have been recommended for the treatment of complete acromioclavicular separation. Uncertainty regarding the way of surgical treatment leads to a distinct reduction in the number of case reports by individual authors. In consequence we established a uniform concept of surgical treatment, namely dynamic stabilisation. All patients who were operated on since 1975 were treated accordingly. Our results were in accordance with the high rates of metal breakage and loosening reported by other authors. Never the less, the functional results after surgical treatment still justify this concept of management. PMID- 2874705 TI - [Causes, therapy and results of operative treatment of recent and old acromioclavicular joint dislocations]. AB - Osteosynthesis with wires and cerclages is the operative technique of choice in case of recent or old breaking of acromio-clavicular joint. In case of an old lesion of the acromio-clavicular joint syndesmoplasty should be performed only if direct suture of the ligaments is no longer possible. The so-called "allo ligament" proved to be a failure because of the high rate of infections. The "Kirschner wires" should have a thickness of at least 1.5 mm. To avoid stiffness of the operated shoulder there should be an early active functional treatment. The removal of the osteosynthesis material should be performed only after complete healing of the ligaments (3-4 months postoperatively). PMID- 2874706 TI - Tardive dyskinesia in the elderly. AB - Four hundred and twenty-six elderly subjects were assessed for the presence of dyskinetic movements. Dyskinetic movements were present in 49 subjects (11.5%). Ninety-two per cent had orofacial movements, by far the commonest being chewing. Dyskinetic movements were present in 12.5% of women and 7.6% of men. Abnormal movements were present in 8% of the subjects who had never received neuroleptic drugs and in 20.8% of those who had. There was a statistically significant association between developing dyskinetic movements and receiving chlorpromazine and flupenthixol. There was no association between either advancing age or dementia and dyskinetic movements. PMID- 2874707 TI - [Granulomatous gingivitis and vasculitis]. PMID- 2874708 TI - Genetics of esterases and 6-phosphogluconate dehydrogenase in the Anopheles maculatus complex. AB - Electromorphic variation for some esterases and 6-phosphogluconate dehydrogenase enzymes in the Anopheles maculatus complex is controlled by four loci which are unlinked to sex. Esterase loci are linked to each other: Est-1-36%-Est-4-16.5% Est-3; but unlinked to Pgd-2. Linkage data were obtained by selfing the F1 generation from selected parents and analysing genotypes in the F2; the classical dihybrid-cross. The analysis consists of testing observed data for goodness of fit to a) ratios expected from Mendelian ratios without linkage and b) if they do not fit then computing a likely degree of linkage and computing expected ratios with such linkage for further tests. Confidence limits are given for the most likely levels of linkage. This method can provide useful information for population-genetic studies on anopheline mosquitoes, whose laboratory rearing is generally difficult. Through indirect evidence, the enzyme loci are correlated to polytene chromosomes. The esterases probably lie on chromosome three (polytene arms 3 and 4) and Pgd-2 on the second chromosome (arms 2 and 5). PMID- 2874709 TI - Quantitative determination of chloroquine and desethylchloroquine in biological fluids by high performance thin layer chromatography. AB - A high performance thin layer chromatographic (HPTLC) method for chloroquine (CQ) and desethylchloroquine (DCQ) determinations in plasma, erythrocytes and urine is described. Samples extracted by heptane from an alkaline water phase are separated on HPTLC silica gel plates, using toluene/diethylamine (9:1). The compounds are quantified by scanning fluorescent signals. The detection limit is 0.01 mumol/1 for CQ and DCQ, with an extraction efficiency of 76 +/- 7%. Further simplification could make the method suitable for use in field surveys. PMID- 2874710 TI - Detection of Dirofilaria immitis microfilariae in peripheral blood. A quantitative comparison of the efficiency and sensitivity of four techniques. AB - Four techniques for the detection and quantification of Dirofilaria immitis microfilariae in peripheral blood were compared, namely the conventional thick smear, thick films prepared by cytocentrifugation, filtration of blood through polycarbonate membranes, and density gradient centrifugation followed by membrane filtration. The efficiency of the methods and their sensitivity was assessed by determining quantitatively the recovery of known numbers of microfilariae from defined volumes of blood. Polycarbonate membrane filtration either alone or in combination with density gradient centrifugation showed an efficiency of 0.9 and 0.8, respectively, and reached 100% sensitivity with microfilariae densities of greater than or equal to 10 microfilariae per ml of blood. Conventional thick smears and cytocentrifugation were of considerably lower efficiency (0.02 and 0.03, respectively) and reached 100% sensitivity with more than 200 microfilariae per ml. PMID- 2874711 TI - Comparison of ultrasonography, intravenous pyelography and cystoscopy in detection of urinary tract lesions due to Schistosoma haematobium. AB - The use of ultrasound in detecting urinary tract alterations by Schistosoma haematobium such as hydronephrosis and bladder calcifications was studied in 125 patients of the out-patients department of a district hospital in SE Tanzania, in an area highly endemic for this disease. Ultrasound was compared with plain abdominal X-ray (in 33 patients), intravenous pyelography (29), cystoscopy (31) and simple urine examination (125). Except for bladder calcifications which could not be demonstrated other than by X-ray, sonography compared favorably with IVP and cystoscopy and proved therefore to be a valuable tool in assessing S.h. related morbidity. In children moderate and advanced hydronephrosis were always associated with an irregular bladder wall and correlated strongly with the prevalence and intensity of S.h. infections as well as with haematuria and proteinuria. Important congestive pathology was observed in 1 out of 10 infected children and in 1 out of 20 examined adults. PMID- 2874712 TI - Epidemiological studies on Schistosoma bovis in Iringa Region, Tanzania. AB - Various aspects of the epidemiology of Schistosoma bovis were studied over a one year period in Iringa Region, Tanzania. An abattoir survey revealed an overall prevalence rate of 30.8% in cattle and 3.8% in goats in the area, and field studies on two dairy farms both providing good opportunities for schistosome transmission provided information concerning the transmission ecology of S. bovis in relation to different types of grazing and water supply. The traditional management system on one farm with a large number of cattle utilizing a limited water resource highly suitable for sustaining populations of the snail host Bulinus africanus resulted in intensive transmission as evidenced by uptake of massive infections in calves and development of resistance to S. bovis challenge in dairy cows. On another farm, appropriate management comprising watering of cattle at a B. africanus-free pond provided the background for less intensive transmission in that transmission risk was confined to occasional contact with water contact sites of secondary importance. Besides, the transmission pattern as regards intensity and seasonality was affected markedly by the geographical and seasonal distribution of the host snail B. africanus. Thus, transmission in canals and temporary ponds was limited mainly to the dry season and the end of the rainy season, respectively, while transmission in permanent ponds occurred intermittently throughout at least most of the year. It is concluded that prevention of severe loss of productivity in domestic ruminants due to schistosome infections should be possible using strategic management procedures provided that essential information is available concerning the pattern of transmission in the particular area. PMID- 2874713 TI - Chemotherapy of East Coast fever. Treatment of infections induced by isolates of Theileria parva with halofuginone. AB - Cattle were infected with three isolates of Theileria parva and treated with halofuginone lactate during acute clinical disease. The health, weight gain and carrier state of the cattle were monitored for 15 months. Limited treatment rapidly reduced fever and parasitosis but parasite recrudescences occurred and 12 out of 21 treated cattle died. Persistent carrier states were identified with two T. p. parva isolate infections and a transient carrier state with T. p. lawrencei. Three cattle which died from a chronic wasting syndrome during the follow-up period showed exhaustion of lymph nodes but no Theileria macroschizonts were detected in any tissue. PMID- 2874714 TI - Frequent occurrence of hepatic lesions in boutonneuse fever. AB - Seven consecutive Sicilian patients with boutonneuse fever but without clinical symptoms of hepatic disease underwent hepatic biopsy and had similar hepatic lesions. Foci of hepatocellular necrosis were infiltrated with predominantly mononuclear leukocytes. No intact Rickettsia conorii were identified in the tissues by immunofluorescence. The apparent high frequency of viscerotropism in boutonneuse fever conforms to the recent observations of severe illness in what had often been described previously as a benign rickettsiosis. PMID- 2874715 TI - Trypanosoma brucei infection in domestic pigs in a sleeping sickness epidemic area of Uganda. Short communication. PMID- 2874716 TI - Nitrate content of ground water is not a valid indicator of faecal pollution in rural Sahel regions. Short communication. PMID- 2874717 TI - Plants in traditional medicine. Medical concepts of the Abelam people in Papua New Guinea. Short communication. PMID- 2874718 TI - [Studies on gamma-glutamyl transpeptidase (gamma-GTP) in seminal plasma]. AB - The significance of gamma-GTP (gamma-glutamyl transpeptidase) in seminal plasma was examined by measuring the gamma-GTP activity in ejaculate, seminal plasma, prostatic secretion, testis, epididymis, vas deferens, prostate and sperm. The gamma-GTP activity was measured spectrophotometrically (405 nm) using L-gamma glutamyl-p-nitroanilide as a substrate. One unit of enzyme activity was defined as the amount liberating 1 mumol of p-nitroaniline per min. The mean gamma-GTP activity was 9,094 +/- 4,351 mU/ml in ejaculate and 7,487 +/- 4,286 mU/ml in seminal plasma of 76 men visiting the infertility clinic. There is a positive correlation between gamma-GTP activity in ejaculate and in seminal plasma. The gamma-GTP activity was 15,044 +/- 6,422 mU/ml in prostatic secretion and twice as high as the activity in seminal plasma. There was no significant correlation between gamma-GTP activity in seminal plasma and volume of ejaculate, sperm density or sperm motility. The gamma-GTP activity in testicular tissues was 72 +/ 25 mU/mg protein except for two cases in which its activity was not detected (3 years old; retentio testis, 71 years old; prostatic carcinoma, was administered with hormonal medicine). The gamma-GTP activity in prostatic tissues was 133 +/- 68 mU/mg protein. The relationship between the gamma-GTP activity in testicular tissues and Johnsen's mean score count. Judging from the present results together with the previous reports of Rosalki et al (1977) and Simon et al (1978) the prostate seemed to be the major source of gamma-GTP in human semen. PMID- 2874719 TI - [Arteritis and fatty degeneration of the spermatic cord resembling periarteritis nodosa: a case report]. AB - A 23-year old male was admitted to our hospital because of swelling of the left scrotum for one month without any particular past history. Blood count, chemistry, urinalysis, chest X-ray and electrocardiogram revealed normal findings. Scrotal exploration was performed. A soft, dumbbell-like tumor enveloped in a thin membrane was found above the left testis. Pathology revealed fibrinous exudation and fibrinoid necrosis in the whole vessel wall indicating resemblance to the panarteritis in periarteritis nodosa. Some granulomatous lesions with many histiocytes were also noted around these arteries. The findings suggested that a inflammation like periarteritis nodosa had occurred at the spermatic cord and subsequently developed into fatty degeneration in the surroundings. Since local periarteritis nodosa-like lesion may progress to systematic disease, further observation is mandatory for this case. PMID- 2874720 TI - Variation of influenza A (H3N2) viruses isolated in the G.D.R. during 1969-1980 epidemics. AB - A collection of 39 influenza A virus strains of the subtype H3N2 isolated in G.D.R. and of six reference strains were analysed with regard to the antigenic structure of their surface proteins haemagglutinin (HA) and neuraminidase (NA) as well as regarding their polypeptide variations. For the field strains during the drift period from spring 1969 to spring 1980 seven main variations resulted from eight polyclonal sera with the haemagglutination inhibition test, and five main variations from six polyclonal sera with the neuraminidase inhibition test. Using the polyacrylamide gel electrophoresis polypeptide variations in HA, nonstructural proteins NS1, NS2 and nucleoprotein (NP) were detected. It could be shown that, even during one epidemic, strains circulated with different polypeptide composition. With the help of peptide mapping further variations of NP and NS1 were registered. The mechanisms leading to the emergence of new epidemic strains are discussed. PMID- 2874721 TI - Inhibition of subtilisin by influenza virus infected allantoic fluids. AB - Allantoic fluids harvested from embryonated chicken eggs infected with reference strains of influenza A viruses were analysed for subtilisin inhibitor activity. While all acid heat-treated and nontreated virus-infected fluids could reduce subtilisin activity, fluids of FM and Bangkok strains had the greatest inhibitory ability. The degree of subtilisin inhibition closely paralleled the appearance of infectious Bangkok and FM virus in allantoic fluid. Maximum levels were achieved at 48 hr post-infection (p.i.) Ultracentrifugation analyses indicated that the bulk of thermostable inhibitor(s) of 48 hr Bangkok and FM infectious fluids remained in the supernatant rather than sedimenting with the viral pellet. PMID- 2874722 TI - Inhibition of vaccinia virus replication in RK-13 cells by N,N'-bis(methylisatin beta-thiosemicarbazone)-2-methylpiperazine. AB - N,N'-bis(methylisatin-beta-thiosemicarbazone)-2-methylpiperazine in a 100 mumol/l concentration inhibited the reproduction of vaccinia virus in RK-13 cells by about 90%. This compound (bis-IBTMP) had no influence on virus adsorption and on early stages of virus multiplication, but affected virus reproduction from 12 to 24 hr post-infection (p.i.). The incorporation of 3H-thymidine into infected cells increased during first 10 hr p.i., decreasing gradually afterwards. In the infected cells treated with bis-IBTMP the same tendency was observed up to 10 hr p.i., but later on the incorporation level remained unchanged. The uptake of 14C amino acids in the presence of bis-IBTMP was reduced both in vaccinia virus infected and non-infected RK-13 cells. PMID- 2874723 TI - Preparation and characterization of hybridomas secreting monoclonal antibodies to tick-borne encephalitis virus. AB - Monoclonal antibodies (MA) were prepared to two strains of tick-borne encephalitis (TBE) virus: strain 4072 isolated from a patient in the U.S.S.R. and low-pathogenic for mice strain Skalica, isolated from a bank vole (Clethrionomys glareolus) in Slovakia. MA specific to the 4072 and Skalica strains were produced by hybridomas of the KEN (60 clones) and NEK (65 clones) series, respectively. Chromosomal analysis of MA producing 114 hybridoma clones of both series revealed a great variability in the number of chromosomes either in the range of given clones or between individual clones. The hybridoma cells under study possessed a high degree of transformation manifested by good growth in the mouse peritoneal cavity and marked accumulation in ascitic fluid (AF). PMID- 2874724 TI - Two kinds of monoclonal antibodies to tick-borne encephalitis virus. AB - Two types of monoclonal antibodies (MA) of the KEN and NEK series prepared to tick-borne encephalitis (TBE) virus differed in the spectrum of their reactivity in serological tests and in their ability to react with individual representatives of the TBE virus complex. The KEN series MA were induced to the 4072 strain isolated from the blood of a patient in the U.S.S.R. The NEK series MA were prepared to the Skalica strain isolated from a bank vole in Czechoslovakia. Both groups of MA belonged to IgG class, reacted in immunofluorescence (IF) test, but possessed no haemagglutination inhibiting (HI) activity. MA of the NEK series reacted in the IF and complement fixation (CF) tests with all members of the TBE virus complex, except of the Powassan virus. MA of the KEN series had no CF activity and in the IF test, they did not react with Powassan and Langat TP-21 viruses and with the Skalica strain of TBE virus. PMID- 2874725 TI - Comparative detection of herpesviruses in tissue specimens by in situ hybridization and immunofluorescence. AB - The conditions of in situ hybridization for demonstration of herpesvirus genomes in animal and human tissues were tested using the ORWO(R) K6 emulsion. It was possible to localize herpes simplex virus (HSV) genomes in infected mice organs (brain and liver) as well as Epstein-Barr virus (EBV) genomes in tonsils of patients with infectious mononucleosis and in tumour specimens of patients with nasopharyngeal carcinomas. Immunofluorescence (IF) revealed mostly corresponding results. The in situ hybridization is more favourable due to its higher specifity, but it is more time consuming and expensive. IF seems advantageous for screening of a great number of tissues. PMID- 2874726 TI - Characterization of influenza A-1983 epidemic strains by polyclonal and monoclonal antibodies and detection of two co-circulating antigenic variants. AB - Influenza virus strains isolated during 1985 epidemic in Czechoslovakia proved to be antigenically closely related to A/Bangkok/79, A/Philippines/2/83 and A/Texas/77 (all H3N2) viruses, if examined in haemagglutination inhibition (HI) tests with standard polyclonal antisera. If examined in HI tests with monoclonal antibody (MAb) IIB4, the virus isolates could be separated into two groups: those reacting to high titres (about two thirds of the isolates) and those negative with IIB4 (titre of less than 20; rest of the strains). A relationship to MAb IIB4 similar to that of freshly isolated A-H3 influenza virus strains was found with prototype strains A/Belgium/2/81 (highly positive with IIB4, HI titre up to 20 000 per 0.025 ml) and A/Philippines/2/82 (titre less than 20). Examination of the isolate labelled A/Prague/2/83, obtained from a single individual, suggested the existence of two stable and passage-independent lines of a single virus strain, namely one HI+ and the second HI- (highly positive and negative in HI tests with MAb IIB4, respectively). Solid-phase radio-immunoassay with 125I labelled MAb IIB4 of the viruses under consideration showed that binding of virus with antibody had occurred in all cases and that, therefore, the negative results of HI tests with HI- strains were not due to the absence of binding of MAb IIB4 to the respective viral antigen. PMID- 2874727 TI - Preparation and characterization of hybridomas producing monoclonal antibodies against human alpha interferon. AB - Hybridomas producing monoclonal antibodies against human alpha interferon (hu-IFN alpha) were constructed by fusion of NSO myeloma cells with spleen cells of BALB/c mice immunized with purified hu-IFN alpha. Altogether, 527 hybridomas were prepared in two separate experiments. From this cohort of hybridomas, 51 produced monoclonal antibodies against hu-IFN alpha. Seventeen out of fifty one hybridomas produced antibodies with neutralizing capacity for IFN while 34 hybridomas produced monoclonal antibodies with binding ability not accompanied with the neutralization of biological activity of IFN. The specificity of antibodies was determined with 3 types of tests: ELISA, ELISAN (modified ELISA) and neutralization test. Using isotype analysis, it has been found that 23 monoclonal antibodies were of IgM class, 20 were of IgG1 subclass, 4 were of IgG2b and 4 of IgG3 subclass. The average number of chromosomes in hybridomas was between 61.35 and 78.55. Their average doubling time was between 13.95 and 25.76 hrs. PMID- 2874728 TI - Contribution to rapid diagnosis of infectious mononucleosis. AB - By indirect immunofluorescence (IF) technique humoral antibodies to Epstein-Barr virus capsid antigen (EB-VCA) and to cytomegalovirus (CMV) were detected in 47% and 9% of persons with infectious mononucleosis (IM), respectively. In 23% of the patients examined, IgM antibodies to both viruses were detected, while in 8% of them high titres of IgG only were found in the absence of IgM class antibodies to EB-VCA or to CMV. The finding of IgM antibody to EB-VCA was in good correlation with the persisting symptoms of the disease. Discrepancy between the presence of specific IgM and the absence of heterophilic antibodies was observed in some children and in all persons with persistent or recurrent signs of IM. In the latter, specific IgM was found only during exacerbation of the disease, but during remissions IgG antibodies persisted in high levels. Antibodies to Epstein Barr virus nuclear antigen (EBNA) were detected in all chronically ill persons and antibodies to the R-component of Epstein-Barr virus early antigen (EA) were present in the majority of them. PMID- 2874729 TI - Studies on preparation of a tick-borne encephalitis (TBE) vaccine from the Skalica strain. AB - Diethylether-treated vaccine against tick-borne encephalitis (TBE) represents a new type vaccine consisting of lipid-free and antigenically efficient components instead of whole virus particles. The TBE virus strain designated Skalica was used for vaccine preparation. This strain is thermosensitive, produces small plaques under agar overlay, is nonpathogenic for adult white mice following subcutaneous (s.c.) application and causes threshold viraemia in host animals. The vaccine was harmless and immunogenic as evidenced by experiments on white mice. Antibodies to TBE virus strain Ir 13 present in human healthy population of a natural TBE focus showed similar levels when tested with the Skalica strain. The Skalica virus strain can be recommended for preparation of the vaccine against TBE. PMID- 2874730 TI - Effect of maternal varicella-zoster virus infection on the outcome of pregnancy and the analysis of transplacental virus transmission. AB - In result of 20 pregnancies complicated by varicella 11 healthy and 6 defective offspring were born, 2 pregnancies were aborted by the physician and one pregnancy terminated by stillbirth of 3 siblings. Laboratory investigation of 16 pregnancies has shown that transplacental transfer of varicella-zoster (VZ) virus did not occur in 13 cases (81.2%). In 3 cases transplacental transmission of VZ virus was not inconsistent with the laboratory results, clinical course, and epidemiological analysis. Intrauterine VZ virus infection was suggested in one typical case of congenital varicella syndrome and in one healthy newborn according to the presence of high serum antibody levels at the time of maternal antibody decline. In the third case, VZ virus antigen was detected by indirect immunofluorescence in the foetal skin tissue after medical abortion. PMID- 2874731 TI - Thymus-independent antibody production to the antigen of Rickettsia prowazekii. AB - Antibody production has been studied in cotton B-rats and in CBA B-mice during immunization with chemical typhus vaccine (CTV) and during infection with Rickettsia prowazekii. Studies of the immune response to rickettsial antigen in T deficient animals have shown a high immunogenicity of CTV and independence of antibody production on T-lymphocytes. Active antibody synthesis was also observed in B-rats and B-mice during Rickettsia prowazekii infection. The absence of T lymphocyte dependence in experimental animals was tested by administration of sheep red blood cells (SRBC). PMID- 2874732 TI - Induction of chromosomal aberrations in human cells by a temperature-sensitive mutant of herpes simplex virus type 2 and its revertants. AB - The induction of chromosomal aberrations by a temperature-sensitive (ts) mutant of herpes simplex virus type 2 (HSV-2) strain Hg52 (ts 13), its revertants 4-8 and 5-8 and by etalon strains HSV-1 17 syn+ and HSV-2 Hg52 was studied in human fibroblast and lymphocyte cultures. The effect on chromosomes of the revertants was tested at permissive (31 degrees C) and non-permissive (38 degrees C) temperatures. At 38 degrees C the revertants could not induce DNase activity. The present results contribute to the possible role of a herpes-coded nuclease in induction of chromosomal aberrations. PMID- 2874733 TI - A simple and rapid characterization of influenza virus isolates by monoclonal antibodies in radioimmunoassay. AB - Radioimmunoassay (RIA) with infectious allantoic fluid directly bound to solid phase, suitable for detection and further characterization of influenza virus isolates, is described. This simple and rapid method was applied for description of isolates obtained from different regions of Czechoslovakia during influenza epidemic in 1983. The results confirmed that all 13 examined isolates represent influenza A viruses possessing H3 subtype haemagglutinin very similar to haemagglutinin of influenza viruses A/Bangkok/1/79 (H3N2), A/Belgium/2/81 (H3N2) and A/Philippines/2/82 (H3N2), respectively. PMID- 2874734 TI - Effect of oxatomide on calcium ions in smooth muscle. AB - In an attempt to elucidate the mechanism of inhibitory action of oxatomide on smooth muscle against various spasmogens, we studied the effect of this drug on cumulative dose response curves (CDRC) to CaCl2 in guinea pig ileum. We found that oxatomide induces a shift to right and a non-surmountable depression of the maximal response of these CDRC which suggests non-competitive antagonism. Furthermore, oxatomide inhibits 45Ca2+ uptake by guinea pig ileum after acetylcholine stimulation which constitutes strong evidence that inhibition of calcium ion utilization by smooth muscle cells plays a major role in the mode of action of oxatomide. PMID- 2874736 TI - Altered adaptive responses to training by nonselective beta-adrenergic blockade in coronary artery disease. AB - To examine the alterations in adaptive responses to training by nonselective beta adrenergic blockade in patients with coronary artery disease (CAD), 26 patients were studied. Thirteen patients, aged 48 +/- 2 years (mean +/- standard error) were treated with beta-adrenergic blocking agents and another 13, aged 55 +/- 2 years, were control subjects. The 2 groups were similar in terms of initial maximal attainable O2 consumption (VO2max): 24 +/- 1 vs 25 +/- 2 ml/kg/min, patients and control subjects, respectively), and intensity (87 +/- 3.0 vs 88 +/- 2% of attainable VO2max), frequency (4 +/- 0.2 vs 4.0 +/- 0.3 days/week), and duration (12 months) of training. Maximal attainable VO2 increased to the same extent (36% vs 35%) in both groups. Heart rate (HR) at rest decreased to a similar extent in both groups (p less than 0.001). During submaximal exercise at the same exercise intensities, HR decreased in both groups, but to a larger extent in the control group than in the beta-blocker group after training. In the later, the reduced HR during submaximal exercise was solely due to training induced bradycardia at rest. In contrast, the slower HR during submaximal exercise in control subjects after training was attributable to both bradycardia at rest and a smaller increase in HR during submaximal exercise. In both groups, the half-time of HR deceleration after cessation of exercise decreased (p less than 0.005) after training. However, the training-induced decrease in the half time was significantly larger (p less than 0.025) in control subjects than in patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2874735 TI - Systemic and renal vasodilation after beta-adrenoceptor blockade with pindolol: a hemodynamic study on the onset and maintenance of its antihypertensive effect. AB - Pindolol, a beta blocker with considerable partial agonist activity (PAA), was studied in 10 hypertensive subjects. The maximal fall in mean arterial pressure (MAP) was seen 3 to 4 hours after oral dosing with 10 mg of pindolol (-15 +/- 3%, mean +/- SEM). This was caused by a reduction in total peripheral resistance (TPR), which amounted to 25 +/- 4% after 24 hours. Cardiac output increased by 16 +/- 5%. Cardiac filling pressures and pulmonary artery pressure did not change. Increasing the dose of pindolol, from 5 mg twice a day to 15 mg twice a day over a 3-week period, caused no further change in MAP. After 3 weeks, the fall in MAP (-11 +/- 2%) was maintained by reduced TPR (-26 +/- 6%), whereas cardiac output and stroke volume were increased by 16 +/- 6% and 26 +/- 6%. Renal blood flow and glomerular filtration rate did not change. Beta blockers devoid of PAA lower cardiac output, whereas the elevated TPR in hypertension is unchanged. The hemodynamic profile of pindolol essentially differs from that of beta blockers devoid of PAA. PMID- 2874737 TI - The effects of chlorcyclizine-induced glycosaminoglycan alterations on palatal mesenchyme-basal lamina relationships in the mouse. AB - The relationships of mesenchymal cells to the basal lamina underlying regions of the palatal-shelf epithelium that are known to increase in cell density during shelf reorientation are quantitatively different from those of cells underlying neighboring regions that do not increase in cell density. Chlorcyclizine-induced alterations of the extracellular matrix were used to investigate the possible contribution of extracellular matrix to these differences. Chlorcyclizine causes hyaluronate and the chondroitin sulfates to be degraded into pieces with smaller molecular weights and lower charge densities, with little or no effect on their synthesis, and also results in cleft palate. Pregnant CD-1 mice were gavaged with chlorcyclizine on days 10.5, 11.5, and 12.5 of gestation, and the fetuses were harvested on day 13.5. Some palatal shelves were excised immediately and fixed for electron microscopy; other heads were partially dissected and incubated for 4 hr prior to fixation. In normal heads differences in mesenchymal cell configurations are detectable after 4 hr in vitro. Electron micrographs were taken of the epithelial-mesenchymal interface in nasal and oral regions that increased in epithelial cell density and in nasal and oral regions which did not. Several variables of mesenchymal cell configuration were measured in a 500-nm wide zone delimited on photographic prints. Chlorcyclizine-induced glycosaminoglycan alterations resulted in quantifiable, region-specific differences in mesenchymal cell relationships to the basal lamina and in the ultrastructural appearance of the zone immediately subjacent to the basal lamina. These results suggest that the epithelial-mesenchymal interface and sublaminar zone of the nasal and oral regions as well as their active and inactive segments may be constitutively different. PMID- 2874738 TI - A double-blind study comparing an acellular pertussis-component DTP vaccine with a whole-cell pertussis-component DTP vaccine in 18-month-old children. AB - An acellular pertussis-component diphtheria-tetanus-pertussis (AC-DTP) vaccine was compared with a currently licensed, whole-cell pertussis-component DTP (WC DTP) vaccine for reactogenicity and immunogenicity when given as the fourth DTP immunization in sixty 18- to 24-month-old children. Reactions over the first 48 hours were significantly less common in the AC-DTP vaccine recipients, as follows (WC-DTP/AC-DTP): fever, 85%/5%; redness, 70%/12.5%; tenderness, 100%/22.5%; swelling, 35%/10%; fretfulness, 70%/12.5%; anorexia, 35%/2.5%; and vomiting, 10%/0%. Antibody responses to pertussis antigens (agglutinogens, lymphocytosis promoting factor, and filamentous hemagglutinin), diphtheria toxoid, and tetanus toxoid in AC-DTP vaccine recipients were comparable with those in WC-DTP vaccine recipients. The AC-DTP vaccine evaluated in this trial seems to be as immunogenic as WC-DTP vaccine while being markedly less reactogenic. PMID- 2874739 TI - Sudden death in a patient taking neuroleptics. PMID- 2874740 TI - Interaction of epinephrine with isolated rabbit tracheal epithelial cells. AB - l-Epinephrine-mediated effects on intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels in rabbit surface tracheal epithelial cells (tracheocytes) were investigated to understand the difference in potency of epinephrine and isoproterenol compared with that observed in intact tracheal mucosa-submucosa. Epinephrine-mediated increases in cAMP levels reached a maximum in approximately 10 min then decreased; however, cAMP levels remained elevated even after 30 min of incubation with catecholamine. The beta-adrenergic antagonist propranolol partially blocked the dose-dependent increase in cAMP caused by epinephrine. Phentolamine, an alpha-adrenergic antagonist, and inhibitors of cyclooxygenase (ibuprofen, indomethacin, and acetylsalicylic acid) caused a shift to the right of the epinephrine dose-response curve, indicating antagonism of the response to epinephrine. Epinephrine, but not isoproterenol, stimulated the generation and release of prostaglandin (PG) E2, with 1.1 microM producing a half-maximal effect. This effect was antagonized by ibuprofen, phentolamine, and yohimbine, an alpha 2-adrenergic antagonist, but not by propranolol. The alpha 2-adrenergic effect of epinephrine was mimicked by clonidine, which stimulated PGE2 generation and release and caused an increase in cAMP levels in a dose-dependent manner; its effects on PGE2 release were blocked by ibuprofen and yohimbine. Methoxamine, an alpha 1-adrenergic agonist, did not stimulate PGE2 release. PGE2 alone caused a time- and dose-dependent increase in cAMP levels. In the presence of clonidine and isoproterenol, PGE2 was released, and the dose-dependent increase in cAMP levels mediated by isoproterenol was shifted to the left, indicating increased potency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2874741 TI - Decreased alpha 1-adrenergic receptor-mediated inositide hydrolysis in neurons from hypertensive rat brain. AB - The expression of alpha 1-adrenergic receptors and norepinephrine (NE)-stimulated hydrolysis of inositol phospholipid has been studied in neuronal cultures from the brains of normotensive (Wistar-Kyoto, WKY) and spontaneously hypertensive (SH) rats. Binding of 125I-2-[beta-(4-hydroxyphenyl)-ethyl-aminomethyl] tetralone (HEAT) to neuronal membranes was 68-85% specific and was rapid. Competition inhibition experiments with various agonists and antagonists suggested that 125I HEAT bound selectively to alpha 1-adrenergic receptors. Specific binding of 125I HEAT to neuronal membranes from SH rat brain cultures was 30-45% higher compared with binding in WKY normotensive controls. This increase was attributed to an increase in the number of alpha 1-adrenergic receptors on SH rat brain neurons. Incubation of neuronal cultures of rat brain from both strains with NE resulted in a concentration-dependent stimulation of release of inositol phosphates, although neurons from SH rat brains were 40% less responsive compared with WKY controls. The decrease in responsiveness of SH rat brain neurons to NE, even though the alpha 1-adrenergic receptors are increased, does not appear to be due to a general defect in membrane receptors and postreceptor signal transduction mechanisms. This is because neither the number of muscarinic-cholinergic receptors nor the carbachol-stimulated release of inositol phosphates is different in neuronal cultures from the brains of SH rats compared with neuronal cultures from the brains of WKY rats. These observations suggest that the increased expression of alpha 1-adrenergic receptors does not parallel the receptor-mediated inositol phosphate hydrolysis in neuronal cultures from SH rat brain. PMID- 2874742 TI - Central cholinergic control of vasopressin release in conscious rats. AB - Intracerebroventricular (icv) administration of carbachol into conscious rats evoked a substantial increase in vasopressin secretion and blood pressure in a dose-dependent manner. These effects were blocked by pretreatment with the muscarinic blocker, atropine (10 micrograms icv), but not by the nicotinic blocker, hexamethonium (10 micrograms icv). Hexamethonium did, however, block the increase in blood pressure, the decrease in heart rate, and the very small elevation in the plasma vasopressin concentration induced by nicotine (10 micrograms icv). These results indicate that stimulation of either central nicotinic or muscarinic receptors can affect the cardiovascular system and suggest that the cholinergic stimulation of vasopressin secretion may involve primarily muscarinic receptors in the conscious rat. PMID- 2874743 TI - In vivo pulsatility of pancreatic islet peptides. AB - In vivo oscillations of pancreatic peptides are recognized in primates. To determine whether such oscillations also occur in other mammalian species and to examine their underlying mechanisms, portal vein levels of insulin, C-peptide, glucagon, somatostatin, pancreatic polypeptide (PP), and glucose were measured simultaneously at 1- or 2-min intervals in nine conscious dogs. For comparison with primates, additional experiments were conducted in baboons and humans. Computer-assisted pulse identification for both raw and smoothed data was performed and spectral estimations calculated after detrending. Concomitance and comovement between the fluctuations of the various peptides and glucose were tested. Prominent pulses at 10- to 14-min intervals were detected most regularly for insulin and glucagon and were frequently reflected in PP and somatostatin levels. Corresponding relative increments in plasma concentration averaged 54% for insulin, 16% for glucagon, 25% for PP, and 24% for somatostatin. Insulin pulses were concomitant with glucagon pulses in 80% of the cases. Pulses of PP were less frequent, although consistently associated with insulin pulses. Somatostatin pulses were less consistently associated with those of other peptides. Peptide oscillations were unrelated to glucose changes. Spectral analysis confirmed these results with peaks in the 10- to 14-min range for all peptides but no significant periodicity for glucose. No consistent delays or advances between the oscillations of the various peptides could be demonstrated. It is speculated that oscillatory behavior in the pancreas may be related to a central pacemaker mechanism, which involves insulin tightly coupled to glucagon, entraining the fluctuations of PP, and, inconsistently, of somatostatin. PMID- 2874744 TI - ATP-dependent proton transport in human renal medulla. AB - An electrogenic proton-translocating ATPase (H+-ATPase) has been described in turtle urinary bladder and bovine and rat renal medulla. In the present study, a membrane fraction with ATP-dependent H+ transport activity was isolated from human renal medulla. Intravesicular acidification was assessed by acridine orange absorbance changes. Proton transport was abolished by N-ethylmaleimide but not oligomycin or vanadate, differentiating this H+-ATPase from mitochondrial F0-F1 H+-ATPase and gastric H+-K+-ATPase. In addition, vesicular proton uptake was demonstrated to be independent of sodium and potassium cotransport. Proton translocation rate increased when transmembrane potential was clamped with valinomycin supporting an electrogenic mechanism. Hydrogen ion transport was dependent on the presence of chloride or bromide, since substitution by fluoride or nitrate markedly decreased intravesicular acidification. The transport characteristics of this proton-translocating ATPase are similar to those described for turtle urinary bladder and bovine and rat renal medulla, which have been assumed to play a role in urinary acidification by the medullary collecting duct. PMID- 2874745 TI - Effect of focal cooling of central chemosensitive areas on cerebral ischemic response. AB - The ventrolateral medullary surface (VMS) has been shown to have chemosensitive areas that can alter blood pressure and respiration. It has also been shown that lesions near the VMS can affect the intensity of the cerebral ischemic response (CIR). To determine which regions of the central chemosensitive areas of the ventral medullary surface contribute to the pressor response caused by cerebral ischemia, we used focal cooling of the caudal Loescheke's (CL), intermediate Schlaefke's (IS), and rostral Mitchell's (RM) areas of VMS during ischemia of the brain. Experiments were performed on 17 pentobarbital sodium-anesthetized, paralyzed, and artificially ventilated cats after denervation of the vagi and sinoaortic nerves. Bilateral occlusion of the external carotid and vertebral arteries resulted in a significant increase of arterial pressure (from 129 +/- 4 to 174 +/- 8 mmHg, P less than 0.01) and an increase in splanchnic sympathetic activity. However, heart rate and cervical sympathetic activities were not appreciably affected by cerebral ischemia. Bilateral cooling of the IS area to as low as 10 degrees C led to a decrease or disappearance of phrenic activity but failed to affect the magnitude of the pressor response. Also cooling of the CL and RM areas and application of Gelfoam pledgets soaked in lidocaine (4%) to these areas did not affect the CIR. However, covering the whole VMS with 0.2 ml of 4% lidocaine or cold cerebrospinal fluid (10 degrees C) abolished the ischemic reflex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2874746 TI - Fetal vascular pressure and heart rate responses to nonlabor uterine contractions. AB - The purpose of this study was to determine whether there are changes in fetal arterial pressure, venous pressure, or heart rate during nonlabor uterine contractions (i.e., contractures) in late gestation pregnant sheep. To do this, amniotic fluid pressure was continuously recorded using on-line computer techniques and subtracted from fetal arterial and venous pressures. With randomly selected data, there were no statistically significant changes with time in the fetal variables. However, when averaged with respect to time of the contractures, fetal arterial and venous pressures increased significantly during the contractures, and heart rate decreased. In addition, there were small but statistically significant decreases in each of the three fetal variables just before the contractures. Blocking the fetal autonomic nervous system eliminated the decreases in the variables before the contractures as well as the decrease in heart rate during the contractures, but arterial and venous pressure increased normally. Infusion of 1 liter of warmed saline into the amniotic space did not alter the fetal cardiovascular or amniotic fluid pressure changes during contractures. In summary, there are significant fetal cardiovascular changes during nonlabor uterine contractions, and these are consistent with a translocation of fetal blood from the placenta into the fetal body. Although the cause of fetal cardiovascular changes just before the contractures is unknown, they suggest but do not prove that the fetus may provide the signal for the nonlabor uterine contractions to occur. PMID- 2874748 TI - [Problems posed by Alzheimer's disease]. PMID- 2874747 TI - Amebic infections in asymptomatic homosexual men, lack of evidence of invasive disease. AB - A survey for enteric infections in 140 asymptomatic homosexual men who attended a community clinic revealed a high prevalence of infection with Entamoeba histolytica (27.1 per cent) and Giardia lamblia (15.7 per cent). In contrast, the prevalence of elevated indirect hemagglutination (IHA) titers (greater than or equal to 1:128), which indicate invasive amebiasis, was low (5.7 per cent). Our findings suggest that only a limited amount of invasive amebic disease is occurring in this group of homosexual men. PMID- 2874749 TI - The lactam of alpha-guanidinoglutaric acid (1-amidino-2-pyrrolidone-5-carboxylic acid). AB - alpha-Guanidinoglutaric acid (alpha-GGA) has been reported to occur in the cerebral cortex after epileptic seizures. No physical characteristics of alpha GGA have been given. A practical procedure for the preparation of alpha-GGA is reported here. alpha-GGA forms a lactam in aqueous solution at 80 degrees C. It is proposed to substitute this lactam, 1-amidino-2-pyrrolidone-5-carboxylic acid (pAGlu), for pyroglutamic acid (pGlu) at the N-terminal position in neuropeptides to modify their biological characteristics. L(+)-Glutamic acid was reacted with S methylisothiourea (I) at pH 10 in aqueous solution to form L(-)-alpha guanidinoglutaric acid: mp 165-168 degrees C, [alpha]22D = -22.7 (C = 4, 2 M HCl). alpha-GGA reacted promptly with excess reagent to form a salt, S methylisothiourea-alpha-guanidinoglutarate: mp 209-210 degrees C, [alpha]22D = 13.0 (C = 4, 2 M HCl). I was removed from the salt with aqueous picric acid, since I readily formed an insoluble picrate, S-methylisothiourea picrate (mp 225 228 degrees C). Alternatively, the salt was added to a cation exchange column, and the alpha-GGA was eluted with molar ammonium acetate buffer, pH 9.5. Its lactam, 1-amidino-2-pyrrolidone-5-carboxylic acid, mp 248-249 degrees C, [alpha]22D = +2.1 (C = 4, 2 M HCl), formed a picrate (mp 196-199 degrees C). PMID- 2874750 TI - An iodine-125 radioimmunoassay for the direct detection of benzodiazepines in blood and urine. PMID- 2874751 TI - Pharmacologic and clinical aspects of preoperative medication. PMID- 2874752 TI - Increases in intracranial pressure from succinylcholine: prevention by prior nondepolarizing blockade. AB - Whether succinylcholine causes an increase in intracranial pressure (ICP) in patients with brain lesions is uncertain and, if increased ICP does occur, its pathophysiology remains unknown. The authors investigated both the effect of succinylcholine on ICP and its modification with prior neuromuscular blockade by measuring ICP (subarachnoid bolt) in 13 consecutive patients with brain tumors who received succinylcholine both before and after complete neuromuscular blockade with vecuronium. Anesthesia was induced with thiopental, 6 mg X kg-1 iv, and nitrous oxide, 70% in oxygen, while ventilation was controlled (PaCO2 = 37.2 mmHg +/- 1.7 SE). Succinylcholine, 1 mg X kg-1 iv, was administered and ICP, heart rate (HR), and blood pressure (BP) were recorded until normal twitch tension was restored. Complete neuromuscular blockade was then established with vecuronium, 0.14 mg X kg-1 iv; 3 min later, succinylcholine, 1 mg X kg-1 iv, was repeated. The resulting changes in ICP, HR, and BP were recorded for 3 min. Following the first dose of succinylcholine, mean ICP increased from 15.2 mmHg +/ 1.3 SE to 20.1 mmHg +/- 2.0 SE (P less than 0.05), with five of the patients sustaining increases in ICP of 9 mmHg or greater. In contrast, when succinylcholine was given after vecuronium-induced paralysis, no patient developed an increase in ICP greater than 3 mmHg (P less than 0.05 compared with the incidence of ICP greater than or equal to 9 mmHg observed after the first dose of succinylcholine). A second group of six patients received two doses of succinylcholine according to the same protocol but without an intervening dose of vecuronium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2874754 TI - [Information on mosquitoes (Diptera, Culicidae) of Leipzig, East Germany]. AB - With 482 catches between 1949 and 1984, 26 species of the family Culicidae were proved in the district of Leipzig. Anopheles was found in 9 subdistricts. The species were registered according to the subdistrict or region where caught. The species caught in the GDR and in Berlin (West) after 1948/49 were arranged in a table which also includes the authors of catching-publications. Further information on some species has been provided. The findings are documented by cryptograms and adequate symbolic parts. PMID- 2874755 TI - Prevention and treatment of supraventricular tachycardia shortly after coronary artery bypass grafting: a randomized open trial. AB - Supraventricular arrhythmias continue to complicate the postoperative course of patients following coronary artery bypass grafting. In a randomized, open, controlled trial we assessed the value of two different beta-blocking agents in the prevention and treatment of these arrhythmias. Of 151 consecutive patients undergoing coronary artery surgery, 39 were treated with metoprolol and 41 were treated with sotalol (a beta blocker with class III antiarrhythmic properties). Fifty patients served as a control group and received no prophylactic therapy. Twenty-one patients were eliminated from the study for various reasons, making a final total of 130 in the study group. In the metoprolol group 15.3% of patients developed supraventricular tachycardia SVT after coronary artery surgery, which was significantly less (p less than 0.05) than the incidence observed in the control group. However, in the group of patients receiving sotalol, 2.4% developed SVT (p less than 0.01 compared with the control group). Of 18 patients in the control group who developed SVT after randomization, 10 received sotalol and 4 metoprolol to terminate the arrhythmia. The mean time of termination of SVT after drug administration was 2.4 +/- 1.8 hours for treatment with sotalol and 13.6 +/- 9.8 hours for treatment with metoprolol. We conclude that sotalol significantly reduces the incidence of supraventricular tachycardia in the early period after coronary artery bypass surgery. PMID- 2874753 TI - The scientific basis for analgesic use in dentistry. PMID- 2874756 TI - Emergency psychopharmacology: a review and update. AB - The emergency area is a difficult site for the practice of careful psychopharmacology. The detailed history taking and collaborative treatment relationship often found in the consultant's office is rarely present. Instead, rapid decisions are made under a variety of pressures, with patients who may be uncooperative and unwilling to be treated. Many emergency patients are concurrently in treatment with a psychotherapist or psychopharmacologist who is available for consultation to the emergency service. When this is possible it is of great potential value, both in arriving more quickly at an appropriate treatment and in preventing a harmful opposition of the patient's treatment resources. For patients who are not currently in another treatment, additional helpful information often may be obtained from friends or family members. This is especially useful in treating patients who are acutely psychotic, unable to communicate, or uncooperative with the emergency interview. Although psychopharmacological approaches properly chosen often yield rapid results, medications are only a part of most emergency treatment plans. Medications are ineffective in a variety of crises and cannot replace careful interviewing of patients and others aimed at understanding the exogenous stress, change in interpersonal relationships, intrapsychic conflict, or biological disorder that precipitated an emergency visit. Furthermore, the decision to treat with medications must include a consideration of the adverse effects that may occur. With these limitations in mind, the area of emergency psychopharmacology can provide powerful assistance to emergency clinicians. PMID- 2874757 TI - Beta blocker overdoses. PMID- 2874758 TI - Glucagon and beta-blocker poisoning. PMID- 2874759 TI - Independent influence of reversibility of air-flow obstruction and nonspecific hyperreactivity on the long-term course of lung function in chronic air-flow obstruction. AB - We evaluated factors that might influence the course of lung function after 2 to 21 yr of follow-up in 81 nonallergic patients with chronic air-flow obstruction (CAO) and considerable lung function impairment (initial forced expiratory volume in one second as a percentage of inspiratory slow vital capacity (FEV1 % VC) ranging from 40 to 55% and increasing less than 15% after the administration of the anticholinergic bronchodilator thiazinamium). A more favorable rate of change in FEV1 was associated with less pack-years of smoking, less nonspecific hyperreactivity, and a higher degree of reversibility of air-flow obstruction, when expressed as the increase in FEV1 as a percentage of the predicted minus prebronchodilator FEV1 value. Nonspecific hyperreactivity and reversibility of air-flow obstruction appeared to influence the decline in FEV1 independently of baseline value of FEV1, both in smokers and ex-smokers. The hypothesis is put forward that regular bronchodilating therapy may be able to prevent deterioration of lung function. However, the possibility that interval therapy may ultimately produce the same results cannot be excluded. It seems to be important to stop smoking, both for the sake of its negative influence on the course of FEV1 and for the fact that a beneficial influence of bronchodilating therapy may become even more apparent. PMID- 2874760 TI - [Cyclophosphamide in panarteritis nodosa in a child]. PMID- 2874761 TI - Diagnosis of left-sided regurgitant murmurs by transient arterial occlusion: a new maneuver using blood pressure cuffs. AB - Transient arterial occlusion of both arms with blood pressure cuffs inflated to 20 to 40 mm Hg above systolic pressure for 20 seconds augmented the intensity of left-sided regurgitant murmurs caused by aortic regurgitation, mitral regurgitation, and ventricular septal defect. We compared this new maneuver with handgrip exercise, squatting, and amyl nitrite inhalation in 30 patients with left-sided regurgitant murmurs and in 30 patients with murmurs not caused by left sided regurgitation. Transient arterial occlusion increased the intensity of left sided regurgitant murmurs more than squatting (p = 0.02) and did not statistically differ from isometric handgrip exercise and amyl nitrite inhalation in ability to identify the presence of these murmurs. A false-positive diagnosis of left-sided regurgitant murmur was less likely when using transient arterial occlusion than when using handgrip exercise (p = 0.05) and squatting (p less than 0.001). Thus, transient arterial occlusion works as well as or better than other standard bedside maneuvers for diagnosing or excluding left-sided regurgitant murmurs and can be applied to all patients. PMID- 2874762 TI - [Benzonitrile and structural analogs: action of para-nitrobenzonitrile (PNB) on the central nervous system]. PMID- 2874763 TI - Testicular venography in the localization of undescended testes. An analysis of seventeen patients. PMID- 2874764 TI - [Hybridization in situ: methodology and applications to the analysis of phenomena of gene expression in endocrine glands and the nervous system]. AB - Techniques of in situ hybridization for the detection of mRNA on histological sections are described and commented upon. The main applications of the procedure are discussed and the potential uses of this new method for the analysis of gene expression in endocrine and nervous systems are presented. PMID- 2874765 TI - Elevated gamma-aminobutyric acid level in striatal but not extrastriatal brain regions in Parkinson's disease: correlation with striatal dopamine loss. AB - We measured the concentration of gamma-aminobutyric acid (GABA), glutamic acid, and o-phosphoethanolamine in autopsied brain of 9 patients who died with idiopathic Parkinson's disease and 10 control subjects. In the control striatum GABA showed an uneven rostrocaudal distribution pattern with rostral subdivisions containing about 40 to 50% higher levels. When compared with controls, GABA concentrations in Parkinson's disease striatum were generally elevated. The GABA elevation was most pronounced in the caudal subdivision of the putamen; this striatal subdivision also showed the most severe dopamine loss. We observed in the caudal putamen a significant negative correlation between the (elevated) GABA and (reduced) dopamine levels (the latter expressed as the sum of dopamine plus 3 methoxytyramine). Milder nonsignificant elevations of GABA levels were observed in intermediate and rostral putamen followed by the caudate head subdivisions. GABA levels were normal in all extrastriatal brain areas examined. Striatal glutamic acid levels were markedly elevated in 3 of the 9 patients with Parkinson's disease. We suggest that the altered GABA metabolism in the striatum, especially the putamen, is consequent to the nigrostriatal deficiency in this disorder. This secondary change in striatal GABA function is likely to contribute to the basal ganglia dysfunction produced by the striatal dopamine loss and thus may be related to certain aspects of parkinsonian symptomatology. PMID- 2874766 TI - Acidification of the endocytic and exocytic pathways. PMID- 2874767 TI - Discontinuous transcription and antigenic variation in trypanosomes. AB - The main theme of this review is the discontinuous synthesis of mRNAs in trypanosomes. This novel process was discovered in the unicellular eukaryote Trypanosoma brucei, but it is probably a general feature of the order of Kinetoplastida, to which several other major human pathogens belong. Discontinuous RNA synthesis involves a sequence of 35 nucleotides (nt) found at the 5' end of all trypanosome mRNAs analyzed. The 35-nt sequence is encoded in arrays of 1.35-kb repeats that are clustered in the genome. The primary transcript of the 1.35-kb repeat is an RNA of 140 nt that carries the 35-nt sequence at its 5' end. The 35-nt sequence is transferred from the 140-nt precursor to pre-mRNAs made elsewhere in the genome. The process has not yet been reconstructed in vitro, and whether transfer involves priming of pre-mRNA synthesis, RNA-RNA ligation followed by splicing, trans-splicing, or more than one of these mechanisms, is still unknown. Circumstantial evidence makes priming the least likely of these alternatives. Why it is advantageous to trypanosomes to make their mRNAs in such an unusual fashion is unclear. As yet, there is no evidence for discontinuous synthesis of mRNAs in organisms other than kinetoplastid flagellates. The mini-exon sequence was first found in mRNAs for Variant-specific Surface Glycoproteins (VSGs), and the control of the synthesis of these proteins is a second theme of this review. Silent VSG genes may be activated by their duplicative transposition to a telomeric expression site. The transposition process looks like a gene conversion, mediated by short blocks of sequence homology. Activation of the transposed gene is due to its insertion into an active transcription unit, i.e. to promoter addition. Telomeric VSG genes can also be activated without duplication. This can occur by a reciprocal translocation in which a silent telomeric gene exchanges position with a gene residing in an active expression site. A VSG gene may also be activated without detectable translocation, however, by the transcriptional activation of the silent expression site in which it is located. How this occurs is still unknown, because the transcription units are so long that the promoter for pre-mRNA synthesis has not yet been reached by chromosome walking. A simple mechanism in which a mobile promoter moves between telomeres has been rendered unlikely by the demonstration that two telomeric transcription units can be simultaneously active when one of them is interrupted by a large DNA insertion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2874768 TI - Brain serotonin and eating behavior. AB - Studies indicate that hypothalamic monoamine systems involved in the control of food intake have specific effects on temporal feeding patterns and on appetite for specific macronutrients. Based on the evidence obtained in rats, it is proposed that serotonin acts, in part, through a satiety mechanism of the medial hypothalamus, to reduce ingestion of carbohydrate while sparing protein intake. In controlling the ratio of carbohydrate to protein intake, this serotonergic system, which is responsive to the anorectic agent fenfluramine, is believed to function in direct opposition to the alpha 2-noradrenergic system of the paraventricular nucleus, which inhibits satiety for carbohydrate and thereby potentiates the size of carbohydrate meals. This serotonergic system may also indirectly oppose the catecholaminergic systems of the lateral hypothalamus, which mediate amphetamine anorexia and which inhibit a hunger-stimulating system for protein intake, thereby delaying the initiation of protein meals. Examination of the rats' normal eating patterns, in conjunction with particular biochemical analyses, has indicated specific points in the circadian eating cycle where these hypothalamic monoamine systems, in association with changes in circulating hormones and nutrients, may be physiologically activated. PMID- 2874769 TI - Serotoninergic mechanisms in human feeding: the pharmacological evidence. AB - This paper reviews the evidence of serotoninergic mechanisms in human feeding by considering the effects of 5-HT agonists, precursors and receptor antagonists on hunger, food intake and weight change in normal volunteers, obese people and psychiatric patients. Although there is compelling evidence for a serotonin (5 HT) mechanism being involved, the paper highlights the considerable individual variation in response to pharmacological manipulation of 5-HT. Such variation may reflect differences in the bio-availability of the drugs used. Subtle psychological factors may also play a role in blurring the pharmacological evidence for 5-HT involvement in the highly complex activity of human feeding. PMID- 2874770 TI - Binding and internalization of atrial natriuretic factor by high-affinity receptors in A10 smooth muscle cells. AB - A10 smooth muscle cells, derived from embryonic rat thoracic aorta, responded to the atrial natriuretic factor (ANF) with increased levels of cyclic GMP. These cells possess high-affinity (apparent Kd = 50 pM) plasma membrane receptors for ANF. Internalization of ANF at 37 degrees C was indicated by the following: approximately 25% of the 125I-ANF associated with the cells at elevated temperatures could not be dissociated from the surface of the cells, but could be released by permeabilization with saponin, and the amount of nondissociable ANF increased in the presence of chloroquine. In whole cells and in membranes, a single polypeptide of 60,000 Da was specifically labeled by a photoaffinity analog of 125I-ANF, as well as by crosslinking, and an IC50 of 80 pM for inhibition of the labeling by ANF was observed. The ANF receptor in A10 cells was distinguished from that in rabbit aorta by its high affinity for shorter and linear analogs of ANF, as well as by a different photolabeling pattern. PMID- 2874771 TI - Biosynthesis of 5-methylaminomethyl-2-selenouridine, a naturally occurring nucleoside in Escherichia coli tRNA. AB - A selenium-containing nucleoside, 5-methylaminomethyl-2-selenouridine (mnm5se2U), is present in lysine- and glutamate-isoaccepting tRNA species of Escherichia coli. The synthesis of mnm5se2U is optimum (4 mol/100 mol tRNA) when selenium is present at about 1 microM concentration and is neither decreased by a high (8 mM) level of sulfur in the medium nor increased by excessive (10 or 100 microM) levels of selenium. Lysine- and glutamate-isoaccepting tRNA species that contain 5-methylaminomethyl-2-thiouridine (mnm5s2U) coexist with the seleno-tRNAs in E. coli cells and a reciprocal relationship between the mnm5se2U- and the mnm5s2U containing species is maintained under a variety of growth conditions. The complete 5-methylaminomethyl side chain is not a prerequisite for introduction of selenium at the 2-position. In E. coli mutants deficient in the ability to synthesize the 5-methylaminomethyl substituent, both the 2-thiouridine and the corresponding 2-selenouridine derivatives of intermediate forms are accumulated. Broken cell preparations of E. coli synthesize mnm5se2U in tRNAs by an ATP dependent process that appears to involve the replacement of sulfur in mnm5s2U with selenium. PMID- 2874772 TI - Psoriasiform cutaneous eruptions induced by cetamolol hydrochloride. PMID- 2874773 TI - Glucocorticoid-induced vasoconstriction in human skin. An inhibitory role on phospholipase A2 activity. AB - The ability of topically applied betamethasone valerate to reduce erythema produced by a variety of vasodilators was assessed. The steroid significantly reduced the erythema induced by topical arachidonic acid, intradermal histamine, and compound 48/80. We postulated that the steroid reduced endogenous phospholipase activity either before or after application of the vasodilators, or both. This action may explain the mechanism of glucocorticoid-induced vasoconstriction in the skin and part of the steroids' action in acute inflammatory skin disease. PMID- 2874774 TI - Allergy and antihistamines. A new riddle. PMID- 2874775 TI - Stabilization of alanine aminopeptidase, gamma glutamyltranspeptidase, and N acetyl-beta-D-glucosaminidase activity in normal urines. PMID- 2874776 TI - [Beta-1 and beta-2 blocking activities of a new series of (arylalkoxy) propanolamines]. PMID- 2874777 TI - [Our experience in the treatment of cryptorchism with HCG]. PMID- 2874779 TI - [Introduction to the problems of stress]. PMID- 2874778 TI - Gastrointestinal peptides in serum and synovial fluid from patients with inflammatory joint disease. AB - The concentrations of immunoreactive vasoactive intestinal polypeptide (ir-VIP), immunoreactive pancreatic polypeptide (ir-PP), ir-somatostatin, and ir-secretin were measured in serum and synovial fluid from patients suffering from various inflammatory joint diseases. One group of patients were not taking any medication, while another group received anti-inflammatory treatment at the time of sampling. High levels of ir-VIP in the synovial fluid were observed in the untreated group of patients, and the concentration of ir-VIP in the synovial fluid was significantly higher than in parallel serum samples. On the other hand, no significant differences in the concentrations of the other peptides were observed either between serum and synovial fluid or between the two groups of patients. It is suggested that VIP is released locally at the inflammatory site and that VIP may be of significance in inflammatory disorders. PMID- 2874781 TI - Behavior management of aggressive sequela after Reye's syndrome. AB - This study describes the use of behavior management procedures to reduce the occurrence of severe behavioral sequela in a 14-year-old, post-Reye's syndrome male. Prior to intervention the client exhibited severe self-injurious, hyperaggressive, and food refusal behaviors that precluded any opportunities for rehabilitation, placed him at severe medical risk, and made him a candidate for institutional placement. With contingent restraint, in vivo desensitization, and reinforcement contingencies it was possible to control these behaviors and begin intensive rehabilitation. Subsequently, the client returned to his family and community day school for the severely handicapped where he remains five years later. PMID- 2874780 TI - Ketazolam once daily for spasticity: double-blind cross-over study. AB - This double-blind cross-over study of 14 severely spastic inpatients with chronic multiple sclerosis reveals that once-daily doses of ketazolam, a new drug, are effective in reducing spasticity in a significant proportion of patients without significant side-effects. Added to the similar findings of an earlier double blind controlled study of divided doses, the results suggest that this special feature of ketazolam provides a unique flexibility that may be exploited in individual cases. PMID- 2874782 TI - Long-term corneal endothelial cell loss after cataract surgery. Results of a randomized controlled trial. Oxford Cataract Treatment and Evaluation Team (OCTET). AB - Three hundred thirty-three eyes were randomly assigned to three treatments for cataract: group A, intracapsular extraction plus contact lens; group B, intracapsular extraction plus Federov implant (Federov I lenses were made by Rayners Ltd, United Kingdom, based on a design by Professor Fyodorov); and group C, extracapsular extraction plus iridocapsular implant. Endothelial cell loss estimated at one and six months and yearly up to four years showed significantly greater loss in the two implant groups from one year onward. Continuing loss slowed down after the third year, except for the intracapsular extraction plus implant group, in which cell loss appeared complication related. Of operative factors, use of alpha-chymotrypsin significantly reduced cell loss, and pseudophakos contact increased cell loss. Postoperative complications associated with significantly greater cell loss were hypopyon, uveitis, subluxation, shallow anterior chamber, and cystoid macular edema. To date, five and four cases of bullous keratopathy were derived from implant groups B and C, respectively. PMID- 2874783 TI - Additive effect of betaxolol and epinephrine in primary open angle glaucoma. AB - Betaxolol hydrochloride is a topical beta 1-blocking agent that has been found to be safe and effective in lowering intraocular pressure (IOP) in patients with glaucoma. We administered open-label epinephrine for four weeks to 19 patients who were already being treated with masked 0.5% timolol maleate or 0.5% betaxolol. In patients receiving betaxolol, epinephrine produced a significant additional lowering of mean IOP from 24.5 +/- 0.7 to 19.4 +/- 0.6 mm Hg at one week (P less than .0001) and to 20.7 +/- 0.5 mm Hg at four weeks (P less than .0001). This was accompanied by a statistically significant increase in mean outflow facility from 0.12 +/- 0.1 to 0.17 +/- 0.03 microL/min/mm Hg at one week (P less than or equal to .05) and to 0.18 +/- 0.02 microliter/min/mm Hg at four weeks (P less than or equal to .004). Consistent with previous reports, patients receiving timolol exhibited no significant changes in IOP or outflow facility after the addition of epinephrine to their treatment regimen. These results suggest that epinephrine's agonist effect on the outflow channels is mediated through beta 2-adrenergic receptors and that combined therapy with betaxolol and epinephrine may be clinically useful. PMID- 2874784 TI - Cellular migration, proliferation, and contraction. An in vitro approach to a clinical problem--proliferative vitreoretinopathy. AB - Presently used animal models of proliferative vitreoretinopathy reflect only cell proliferation and contraction. We used an in vitro model that measured cell migration, proliferation, and contraction. The following four drugs were assayed on this system: daunomycin, taxol, colchicine, and cytochalasin B. Daunomycin was the most effective drug against cell proliferation and cell migration but had no effect on cell contraction; taxol and colchicine affected all three parameters. Cytochalasin B was the least effective drug tested. PMID- 2874785 TI - Cutaneous reactions to drugs. PMID- 2874787 TI - Trauma to the permanent teeth. PMID- 2874786 TI - Cross-protection from Bacteroides nodosus vaccines and the interaction of pili and adjuvants. AB - The effects of vaccination of Merino sheep with the purified pili or the whole cells of Bacteroides nodosus strain 198, either in oil or alum-oil adjuvant, on the severity of foot-rot induced with the homologous strain (198) and a heterologous strain (217) were determined in a field experiment, on flood irrigated pasture. The efficacy of the whole cell vaccines was comparable to that of purified pili vaccines, against homologous challenge, when both had a similar content of pilus antigen although the purified pili vaccines induced significantly greater homologous pilus agglutinating antibody titres than the whole cell vaccines. However, against heterologous challenge, the whole cell vaccines in oil (CO) or alum-oil (CAO) provided significantly greater protection than a purified pili-in-oil (PPO) vaccine, the number of severely affected feet in sheep vaccinated with PPO being similar to that of the unvaccinated group. The group vaccinated with purified pili in alum-oil (PPAO) was intermediate between these two extremes. The superior performance of the PPAO in comparison to the PPO vaccine, against heterologous challenge, was associated with significantly higher mean ELISA titres to the outer membrane complex. Western blot analyses implicated a role in cross-protection for outer membrane proteins, in particular a protein Mr 78,000. The PPO vaccine produced fewer, smaller and less persistent vaccination reactions at the inoculation sites than did the other vaccines. Bodyweight gains in the period prior to challenge were much lower for the groups vaccinated with CO and CAO than for the controls and those vaccinated with purified pili, due presumably to the larger vaccination reactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2874788 TI - Exposure in vivo of obsessive-compulsives under distracting and attention focusing conditions: replication and extension. PMID- 2874789 TI - Streptomyces K15 DD-peptidase-catalysed reactions with ester and amide carbonyl donors. AB - In water, the purified 26 000-Mr membrane-bound DD-peptidase of Streptomyces K15 hydrolyses the ester carbonyl donor Ac2-L-Lys-D-Ala-D-lactate (release of D lactate) and the amide carbonyl donor Ac2-L-Lys-D-Ala-D-Ala (release of D alanine) with accumulation of acyl- (Ac2-L-Lys-D-alanyl-)enzyme. Whereas hydrolysis of the ester substrate proceeds to completion, hydrolysis of the amide substrate is negligible because of the capacity of the K15 DD-peptidase for utilizing the released D-alanine in a transfer reaction (Ac2-L-Lys-D-Ala-D-Ala + D-Ala----Ac2-L-Lys-D-Ala-D-Ala + D-Ala) that maintains the concentration of the amide substrate at a constant level. In the presence of an amino acceptor X-NH2 (Gly-Gly or Gly-L-Ala) related to the Streptomyces peptidoglycan, both amide and ester carbonyl donors are processed without detectable accumulation of acyl enzyme. Under proper conditions, the acceptor activity of water and, in the case of the amide substrate, the acceptor activity of the released D-alanine can be totally overcome so that the two substrates are quantitatively converted into transpeptidated product Ac2-L-Lys-D-Ala-NH-X (and hydrolysis is prevented). Experimental evidence suggests that the amino acceptor modifies both the binding of the carbonyl donor to the enzyme and the ensuing rate of enzyme acylation. PMID- 2874790 TI - The dynamics of phase partition. A study of parameters affecting rat liver organelle partitioning in aqueous two-polymer phase systems. AB - Separation of subcellular organelles by two-phase partition is thought to reflect differential partition of the organelles between the two phases or between one of the phases and the interface. Studies by Fisher and colleagues [Fisher & Walter (1984) Biochim. Biophys. Acta 801, 106-110] suggest that cell separation by phase partition is a dynamic process in which the partition changes with time. This is mainly due to association of the cells with sedimenting droplets of one phase in the bulk of the other. Rat liver organelle partition was studied to determine whether the same dynamic behaviour is observed. Partition was clearly time dependent during 24 h at unit gravity, and was also affected by altering the volume ratio of the two phases and the duration of phase mixing. These results indicate that, as with cells, the partition of organelles between phases is a dynamic process, and is consistent with the demonstration that organelles adhere to the phase droplet surfaces. Optimization of the volume ratio between phases may lead to significant processing economies. Organelle sedimentation in the upper phase was significantly faster than in the isoosmotic sucrose. Theoretical modelling of apparent organelle sizes indicates that aggregation occurs in the poly(ethylene glycol)-rich upper phase. This phenomenon is likely to limit the use of this technique in organelle separations unless means can be found to decrease aggregation. PMID- 2874791 TI - Alterations by peroxisome proliferators of acyl composition of hepatic phosphatidylcholine in rats, mice and guinea-pigs. Role of stearoyl-CoA desaturase. AB - Rats, mice and guinea-pigs were administered p-chlorophenoxyisobutyric acid (clofibric acid) or 2,2'-(decamethylenedithio)diethanol (tiadenol). The treatments of rats and mice with either clofibric acid or tiadenol increased markedly the activities of stearoyl-CoA desaturase, palmitoyl-CoA chain elongation, 1-acylglycerophosphate (1-acyl-GP) acyltransferase and 1 acylglycerophosphocholine (1-acyl-GPC) acyltransferase, but not 2 acylglycerophosphocholine (2-acyl-GPC) acyltransferase in liver microsomes. The treatment of guinea-pigs with clofibric acid did not cause any change in the activities of these enzymes. The treatment of guinea-pigs with tiadenol caused a slight, but significant, increase in the activities of 1-acyl-GP acyltransferase and 1-acyl-GPC acyltransferase. The treatment of rats and mice with either clofibric acid or tiadenol increased markedly the proportion of 18:1 and decreased greatly the proportion of 18:0 in liver microsomal phosphatidylcholine. However, there is a considerable difference in the effects of the two peroxisome proliferators on the composition of polyunsaturated fatty acids in phosphatidylcholine between rats and mice. The treatment of guinea-pigs with either of the two peroxisome proliferators caused no change in acyl composition of phosphatidylcholine. The possible role of stearoyl-CoA desaturation in the regulation of acyl composition of phosphatidylcholine was discussed. PMID- 2874792 TI - A role for transglutaminase in glucose-stimulated insulin release from the pancreatic beta-cell. AB - Preincubation of rat islets of Langerhans with the potent inhibitors of islet transglutaminase activity, monodansylcadaverine (30-100 microM) and N-(5 aminopentyl)-2-naphthalenesulphonamide (100-200 microM), led to significant inhibition of glucose-stimulated insulin release from islets. In contrast, the respective N'-dimethylated derivatives of these two compounds, which did not inhibit islet transglutaminase activity, were much less effective as inhibitors of glucose-stimulated insulin release. None of the compounds inhibited rat spleen protein kinase C activity at concentrations which gave rise to inhibition of glucose-stimulated insulin release. When tested for their effects on calmodulin stimulated bovine heart phosphodiesterase activity, of the compounds that inhibited insulin release, only monodansylcadaverine did not act as an effective antagonist of calmodulin at concentrations (up to 50 microM) that gave rise to significant inhibition of glucose-stimulated insulin release. Furthermore, at 50 microM, monodansylcadaverine did not inhibit methylation of islet lipids. The inhibition of glucose-stimulated insulin release by monodansylcadaverine is therefore likely to be attributable to its interference with islet transglutaminase activity. The sensitivity of islet transglutaminase to activation by Ca2+ was investigated by using a modified assay incorporating dephosphorylated NN'-dimethylcasein as a substrate protein. The Km for Ca2+ obtained (approx. 3 microM) was an order of magnitude lower than previously reported for the islet enzyme [Bungay, Potter & Griffin (1984) Biochem. J. 219, 819-827]. Mg2+ (2 mM) was found to have little effect on the sensitivity of the enzyme to Ca2+. Investigation of the endogenous substrate proteins of islet transglutaminase by using the Ca2+-dependent incorporation of [14C]methylamine into proteins of islet homogenates demonstrated that most of the incorporated radiolabel was present in cross-linked polymeric aggregates which did not traverse 3% (w/v) acrylamide gels. The radiolabelled polymeric aggregates were present in 71 000 g-sedimented material of homogenates, and their formation was transglutaminase-mediated. These findings provide new evidence for the involvement of islet transglutaminase in the membrane-mediated events necessary for glucose-stimulated insulin release. PMID- 2874793 TI - Effect of prior nutritional status on the activity of lipogenic enzymes in primary monolayer cultures of rat hepatocytes. AB - Effect of prior nutritional status of the animal on the activity of lipogenic enzymes and the fatty acid content of cultured hepatocytes was investigated. Hepatocytes were isolated from rats that were starved for 24 h ('starved') or continuously fed ('fed'), or starved for 48 h and then re-fed for 48 h ('re-fed') with a carbohydrate-rich fat-free diet, and maintained as monolayer cultures for 96 h in a serum-free glucose-rich medium (Waymouth's MB752/1) supplemented with insulin, dexamethasone and tri-iodothyronine. The fatty acid content and the activities of acetyl-CoA carboxylase, fatty acid synthase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were determined initially at 3 h after plating and then every 24 h. Initially the activities of all the four enzymes were highest in hepatocytes isolated from the re-fed rats and lowest in those from the starved rats. With time in culture, the activity of all these enzymes increased severalfold (2-5, depending on the enzyme under consideration) in hepatocytes isolated from fed and starved rats, whereas there was a severalfold (2-5) decrease in the activity of these enzymes in hepatocytes isolated from re-fed rats. The initial fatty acid content of the hepatocytes from re-fed rats was 2-3 times that in the other two groups of hepatocytes. The fatty acid content seemed to increase in all three groups of hepatocytes during the 96 h in culture, but these apparent increases were not statistically significant. PMID- 2874794 TI - Translational control of an intestinal microvillar enzyme. AB - The rates of biosynthesis of adult and foetal pig small-intestinal aminopeptidase N (EC 3.4.11.2) were compared to determine at which level the expression of the microvillar enzyme is developmentally controlled. In organ-cultured explants, the rate of biosynthesis of foetal aminopeptidase N is only about 3% of the adult rate. The small amount synthesized occurs in a high-mannose-glycosylated, membrane-bound, form that is processed to the mature, complex-glycosylated, form at a markedly slower rate than that of the adult enzyme. Extracts of total RNA from adult and foetal intestine contained comparable amounts of aminopeptidase N mRNA, encoding gel-electrophoretically identical primary translation products. Together, these data indicate that the expression of aminopeptidase N is controlled at a translational level. PMID- 2874795 TI - The frayed N-terminal of the inhibitor protein of bovine mitochondrial F1-ATPase. AB - The N-terminal region of the bovine mitochondrial F1-ATPase inhibitor protein is frayed. In three independently isolated samples about 62% of chains start at glycine-1. A further 22% of chains start at residue 2, serine, and the remainder at residue 3, glutamic acid. No evidence can be found for alpha-N-formylglycine reported previously. The fraying may be a consequence of proteolytic processing of the precursor of the inhibitor protein during entry into the mitochondrion. PMID- 2874796 TI - Sites of protein-protein interaction on the mitochondrial F1-ATPase inhibitor protein. AB - We have investigated the structure of the mitochondrial F1-ATPase inhibitor protein from ox heart by using a differential trace-labelling method. This method has also been used to determine sites on the inhibitor protein involved in binding to both the isolated mitochondrial ATPase (F1) and to a specific anti inhibitor antibody. Native, free inhibitor was trace-labelled on its lysine and serine residues with [14C]acetic anhydride, and inhibitor protein unfolded in guanidinium chloride or specifically bound to another protein, with [3H]acetic anhydride. Exposure/concealment of residues was deduced from the 14C/3H ratios of the peptides in a proteolytic digest of the inhibitor, after separation by h.p.l.c. None of the lysine or serine residues in the native inhibitor are as exposed as in the unfolded form. There is a gradient of reactivity, with residues 54-58 being most concealed and exposure increasing towards either end of the protein. A slight decrease in reactivity is noted in residues 1-3, suggesting that the N-terminus may be in a fairly restricted environment. These findings are discussed in the light of the predicted structure of the inhibitor protein. All but one of the labelled residues increases in reactivity when inhibitor protein binds to F1. The exception, Lys-24, is only slightly concealed. Hence, F1 binding appears not to involve the lysine or serine residues directly. This finding is consistent with the view that the F1-inhibitor interaction is hydrophobic in nature. Complementary information was provided using an anti-inhibitor antibody that binds to a site on the inhibitor different from that at which F1 binds. Binding of this antibody conceals residues 54, 58, and 65 considerably. This confirms that F1 does not interact with these hydrophilic residues on the inhibitor protein. PMID- 2874798 TI - Induction of desensitization by phorbol ester to beta-adrenergic agonist stimulation in adenylate cyclase system of rat reticulocytes. AB - Treatment of rat reticulocytes with a phorbol ester, tetradecanoyl phorbol acetate (TPA), resulted in the desensitization of adenylate cyclase to the beta adrenergic agonist stimulation depending on the dose and period of the TPA treatment. Treatment of the reticulocytes with TPA caused approximately 40% reduction in the stimulation by beta-adrenergic agonists of adenylate cyclase activity, whereas the treatment had little effect on the basal activity and the activation by fluoride and guanine nucleotide of the enzyme system. No change in the number of beta-adrenergic receptors was observed after the TPA treatment. Treatment with 1-oleoyl-2-acetyl-glycerol (OAG), an activator of protein kinase C, also caused the desensitization of reticulocyte adenylate cyclase to isoproterenol. On the other hand, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a potent inhibitor of protein kinase C, prevented the desensitization induced by TPA. These results suggest the involvement of protein kinase C in a process of desensitization of adenylate cyclase system to beta-adrenergic agonists in rat reticulocytes. PMID- 2874797 TI - Reactivity of a functional carbonyl moiety in bovine aortic lysyl oxidase. Evidence against pyridoxal 5'-phosphate. AB - Previous studies have pointed towards a cofactor role for pyridoxal 5'-phosphate (PLP) in lysyl oxidase, the enzyme that generates the peptidyl aldehyde precursor to the lysine-derived cross-linkages in elastin and collagen. The nature of a carbonyl moiety in purified bovine aortic lysyl oxidase was explored in the present study. A PLP dinitrophenylhydrazone could not be isolated from lysyl oxidase, although corresponding preparations of aspartate aminotransferase, a PLP dependent enzyme, yielded this derivative, as revealed by h.p.l.c. Analysis of lysyl oxidase for PLP after reduction of the enzyme by NaBH4, a procedure that converts PLP-protein aldimines into stable 5'-phosphopyridoxyl functions, also proved negative in tests using monoclonal antibody specific for this epitope. Lysyl oxidase was competitively inhibited by phenylhydrazine, and inhibition became irreversible with time at 37 degrees C, displaying a first-order inactivation rate constant of 0.4 min-1 and KI of 1 microM. [14C]Phenylhydrazine was covalently incorporated into the enzyme in a manner that was prevented by prior modification of the enzyme with beta-aminopropionitrile, a specific active site inhibitor, and which correlated with functional active-site content. The chemical stability of the enzyme-bound phenylhydrazine exceeded that expected of linkages between PLP and proteins. The absorption spectrum of the phenylhydrazine derivative of lysyl oxidase was clearly distinct from that of the phenylhydrazone of PLP. It is concluded that lysyl oxidase contains a carbonyl cofactor that is not identical with PLP and that is bound to the enzyme by a stable chemical bond. PMID- 2874799 TI - Covalent binding to apoprotein is a major fate of heme in a variety of reactions in which cytochrome P-450 is destroyed. AB - The heme in rat liver microsomal cytochrome P-450 was labeled with 14C or 3H and the microsomes were fractionated after in vitro incubations with a variety of agents known to destroy cytochrome P-450 heme. A major fraction of the heme label was irreversibly bound to apoprotein in all cases, including incubations with fluroxene, 1-octene, vinyl bromide, trichloroethylene, vinyl chloride, parathion, cumene hydroperoxide, NaN3, or iron-ADP complex. Label was also extensively bound to apoprotein when purified and reconstituted cytochrome P-450 was incubated with NADPH and vinyl chloride. This process appears to be widespread and involved to a significant extent in the cytochrome P-450 heme destruction observed with many compounds. PMID- 2874800 TI - Diacylglycerol amplifies the induction in vivo of tyrosine aminotransferase and ornithine decarboxylase by glucocorticoid. AB - In adrenalectomized rats, diacylglycerol, a potent activator of protein kinase C, specifically enhanced the induction of tyrosine aminotransferase and ornithine decarboxylase by even maximally effective doses of dexamethasone phosphate, but itself had no effect on these enzyme inductions in the absence of glucocorticoid. The amplifications of enzyme induction by diacylglycerol was dose-dependent and the time courses of the amplified inductions were similar to those of the inductions by dexamethasone phosphate alone. Since diacylglycerol did not affect the induction of these enzymes by glucagon and insulin, its amplifying effect seemed to be specific for induction by glucocorticoids. PMID- 2874801 TI - Polyethylene glycol-modified hemin having peroxidase activity in organic solvents. AB - Hemin, having two carboxyl groups, was coupled with monomethoxypolyethylene glycol, PEG, through the ester bond formed with carbodiimide. The PEG-modified hemin was readily soluble not only in neutral aqueous solution but also in organic solvents. Its absorption spectrum in 1,1,1-trichloroethane showed a sharp Soret band at 398 nm. The modified hemin catalyzed the peroxidase-reaction in organic solvent and in aqueous solution using hydrogen peroxide or peroxidized linolenic acid as hydrogen acceptor and o-phenylene diamine as hydrogen donor. The activity of PEG-hemin in 1,1,1-trichloroethane was greater than that in an aqueous solution; k1 values in 1,1,1-trichloroethane were 2.3 X 10(3) M-1 sec-1 with hydrogen peroxide and 7.0 X 10(2) M-1 sec-1 with peroxidized linolenic acid, and the value in an aqueous solution was 3.0 X 10 M-1 sec-1 with hydrogen peroxide. PMID- 2874803 TI - Localisation of the hydrophilic C terminal part of the ATP synthase subunit 8 of Saccharomyces cerevisiae. AB - The hydrophobic subunit 8 of the yeast ATP synthase was modified using the non penetrating amino reactive specific reagent: isethionylacetimidate. The polypeptide was modified when using the isolated ATP synthase and sodium bromide treated submitochondrial particles. It is shown that the only lysine of the protein was modified by the reagent. It is concluded that the hydrophilic C terminal part of the protein containing lysine 47 is located on the inner side of the inner mitochondrial membrane. PMID- 2874802 TI - Thyroxine-induced changes in rat liver mitochondrial ubiquinone. AB - Ubiquinone was extracted from liver mitochondria isolated from euthyroid and hyperthyroid rats. The redox state of ubiquinone was determined during States III and IV respiration with succinate or glutamate-malate substrates. Ubiquinone was more reduced during State III or IV in the hyperthyroid mitochondria with either substrate. Furthermore, the concentration of ubiquinone increased in the hyperthyroid rats. PMID- 2874804 TI - Inhibition of adenylate cyclase by transglutaminase-catalyzed reactions in pigeon erythrocyte ghosts. AB - We report the occurrence in pigeon erythrocytes of a soluble Ca2+-dependent transglutaminase (TGase) activity. The effect of the erythrocyte ghost protein modifications, determined by TGase-catalyzed reactions, on adenylate cyclase, phospholipid methyltransferase I and II activities and on the lipidic matrix fluidity of the membrane was investigated by using a purified guinea pig liver TGase preparation. The results showed a significant inhibitory effect of such modifications both on the basal and on the variously stimulated (by NaF, Gpp(NH)p alone or in the presence of 1-isoproterenol) adenylate cyclase activity. By contrast, both the phospholipid methylation and the fluidity of the lipidic matrix of the membrane were unaffected by TGase-mediated reactions. These data suggest a new possible inhibitory mechanism of the cyclic AMP synthesis which might be triggered by the enhancement of the cytosolic Ca2+ concentration. PMID- 2874805 TI - Preparation and binding of radioactively labeled porcine transforming growth factor type beta. AB - This report describes the labeling of porcine transforming growth factor type beta (TGF-beta) with 125-iodine. Its binding to NRK cells and three other cell lines has been examined. The data indicate that NRK cells exhibit approximately 10,000 receptors for porcine TGF-beta per cell, with an apparent dissociation constant of 45 pM. The binding of porcine 125I-TGF-beta can be blocked by porcine, murine and human TGF-beta but not by several well characterized growth factors. In all respects examined, the binding observed with porcine 125I-TGF beta appears to be the same as that observed with human TGF-beta. The findings reported here argue that porcine 125I-TGF-beta can be used to quantitate TGF-beta receptors on a wide range of mammalian cells. PMID- 2874807 TI - The effect of mevinolin on cytosolic acetoacetyl coenzyme a thiolase activity in Chinese hamster ovary fibroblasts. AB - The effects of mevinolin on cytosolic acetoacetyl CoA thiolase activity were studied in wild type Chinese hamster ovary fibroblasts and in CHO cells adapted to growth in high levels of mevinolin. Acetoacetyl CoA thiolase, HMG CoA synthase and HMG CoA reductase activities were elevated in the mevinolin resistant line, KH 2.0. Thiolase activity was also increased when wild type cells were incubated for 5 days with 1 micron mevinolin. These results are consistent with the hypothesis that the regulation of the first three enzymes in the cholesterol biosynthetic pathway is mediated at least in part via a common mechanism. PMID- 2874806 TI - Modification of Glu 58, an amino acid of the active center of ribonuclease T1, to Gln and Asp. AB - Glu 58 is one of the amino acids which participates in its catalytic action of ribonuclease T1. We mutated this residue to Gln 58 or Asp 58 by genetic engineering using chemically synthesized genes. The mutant enzymes were expressed in E. coli as fused proteins and purified to homogeniety on SDS-PAGE after cleavage with cyanogen bromide. Their activities in hydrolyzing pGpC were reduced to 10% in the Asp 58 mutant and about 1% in the Gln 58 mutant compared to that of the wild-type enzyme. These results suggest that Glu 58 is important but not essential for catalysis of ribonuclease T1. PMID- 2874808 TI - Morphine inhibition of calcium fluxes, neurotransmitter release and protein and lipid phosphorylation in brain slices and synaptosomes. AB - Morphine (1-100 microM) was found to inhibit several concomitant events in brain slices and synaptosomes which are augmented by depolarizing agents. Thus, 45Ca2+ uptake, amino acid neurotransmitter release, increases in 3',5' cyclic AMP levels and 32Pi incorporation to proteins and lipids induced by veratrine (25 microM) and by potassium (56 mM), were each inhibited in a dose related manner. These inhibitory actions of morphine were all prevented by naloxone (1 microM). Evidence is presented that morphine binding to a receptor on the synaptic membrane affects intracellular mechanisms involved in neurotransmitter release possibly via a second messenger system. An enhancing action of GTP on the inhibitory influences of morphine suggests that its actions are mediated at least in part, via a coupling of the receptor to adenyl cyclase in the outer membrane. This is supported by its inhibitory action on the capacity of depolarizing agents to increase cyclic AMP levels. PMID- 2874809 TI - Biliary excretion of gamma-glutamyltransferase. Selective enhancement by acute ethanol administration. AB - To study the acute effect of ethanol on various constituents of the bile, female Wistar rats received by intravenous administration 0.9% NaCl solution either alone or containing in addition ethanol (0.1 ml ethanol 96% hr-1 100 g body weight-1). Compared to saline-treated controls there was a significant enhancement of biliary gamma-glutamyltransferase excretion after ethanol infusion for 5 hr by 166% (22.1 +/- 2.8 microU/min/100 g body weight vs. 58.2 +/- 13.7; P less than 0.0125), whereas no changes or only marginal alterations have been observed for bile flow and the biliary excretion of total bile acids and alkaline phosphatase. The selective enhancement of biliary gamma-glutamyltransferase excretion by ethanol can be ascribed to an increased solubilization of the membrane-bound enzyme originating from the bile canaliculi of the hepatocytes and/or the epithelial cells of the bile ducts. Since the biliary excretion of total bile acids remained unchanged by ethanol, the observed selective solubilization of gamma-glutamyltransferase may occur by a mechanism primarily not involving total bile acids and could be linked to a direct effect of ethanol on physico-chemical properties such as an increased fluidity of liver plasma membranes. PMID- 2874810 TI - Characterization of alpha 1- and alpha 2-adrenoceptors directly associated with basolateral membranes from rat kidney proximal tubules. AB - We have used 2-(beta-(3-125iodo-4-hydroxyphenyl)-ethylaminoethyl)-tetr alo ne ([125I]HEAT or BE2254), an alpha 1-selective antagonist, and [3H]yohimbine, an alpha 2-selective antagonist, to demonstrate and characterize binding sites in basolateral membranes from rat kidney cortex. Parathyroid hormone (PTH) stimulated the adenylate cyclase activity of the basolateral membranes, whereas thyrocalcitonin, arginine vasopressin (AVP) and isoproterenol did not. Therefore, the basolateral membranes were probably derived from the proximal tubules. The specific binding of [125I]HEAT and [3H]yohimbine to basolateral membranes was rapid, reversible, saturable and of high affinity. The maximum densities of alpha 1- and alpha 2-receptors were 364 and 1130 fmoles/mg protein, indicating that the ratio of alpha 1- to alpha 2-adrenoceptors was about 1:3. The specific binding of [125I]HEAT and [3H]yohimbine to the basolateral membranes was displaced by various adrenergic agents in a manner that suggests that the labeled sites probably represent alpha 1- and alpha 2-adrenoceptors respectively. These results suggest that the binding sites of [125I]HEAT and [3H]yohimbine, which appear to be alpha 1- and alpha 2-adrenoceptors, exist in the basolateral membranes of the proximal tubules. PMID- 2874811 TI - Effect of the antitumor drug caracemide on the neurochemistry of murine neuroblastoma cells (clone N1E-115). AB - Because the antitumor drug caracemide causes neuropsychiatric effects in patients, we investigated its effects on the neurochemistry of cultured neuroblastoma cells (murine clone N1E-115). The drug caused a transient elevation in the level of [3H]cyclic GMP that was not blocked by receptor antagonists or by desensitization of histamine or muscarinic receptors. The EC50 for the response to caracemide was 635 microM. Preincubation of cells with caracemide led to the inhibition of muscarinic receptor-mediated [3H]cyclic GMP formation with an IC50 of 450 microM. Caracemide inhibited basal guanylate cyclase activity in homogenates noncompetitively with a Ki value of 162 microM. The drug also inhibited sodium nitroprusside-stimulated guanylate cyclase in homogenates. Caracemide did not inhibit basal adenylate cyclase activity in either intact cells or homogenates, but inhibited adenylate cyclase activated by prostaglandin E1 (PGE1) or forskolin. The muscarinic receptor-mediated reduction of PGE1 stimulated [3H]cyclic AMP formation was not affected. The Ki for the inhibition of PGE1-activated adenylate cyclase in homogenates was 110 microM. Caracemide was a competitive inhibitor of acetylcholinesterase with a Ki value of 8 microM. The drug did not inhibit, but slightly stimulated, monoamine oxidase activity in N1E 115 cells. The results indicate that caracemide can affect several neurochemical systems in neural cells in culture in a way that correlates with its neuropsychiatric effects. The N1E-115 clone thus appears to be useful for evaluating some of the molecular pharmacological effects of drugs interacting with the nervous system. PMID- 2874812 TI - Effects of an antitumoural rhodium complex on thioacetamide-induced liver tumor in rats. Changes in the activities of ornithine decarboxylase, tyrosine aminotransferase and of enzymes involved in fatty acid and glycerolipid synthesis. AB - Rats were injected daily for 8 weeks with 50 mg of thioacetamide per kg to produce liver tumours. Some of these rats were given three doses of 50 mg of an antitumoural Rh(III) complex/kg at 14, 9 and 5 days before the end of the thioacetamide treatment. Thioacetamide decreased the rate of weight gain of the rats and the Rh(III) complex partly restored it. The activities of ATP citrate lyase, acetyl-CoA carboxylase and fatty acid synthetase in the livers were decreased by thioacetamide treatment and the Rh(III) complex partly reversed this effect. By contrast the activity of malic enzyme was increased by both thioacetamide and the Rh(III) complex and this effect probably relates to NADPH production for detoxification rather than for lipogenesis. Treatment with thioacetamide increased the rate of synthesis of di- and triacylglycerols from glycerol phosphate by liver homogenates, the activity of phosphatidate phosphohydrolase and the incorporation of [3H]glycerol into liver triacylglycerol in vivo. The Rh(III) complex did not produce a significant reversal of these effects of thioacetamide on glycerolipid synthesis. The total uptake of intraportally injected [3H]glycerol by the livers of thioacetamide treated rats was decreased and this was associated with a lowered activity of glycerol kinase. Thioacetamide increased the activity of hepatic ornithine decarboxylase by about 40-fold, but the Rh(III) complex did not reverse this effect. However, the decrease in tyrosine aminotransferase activity that was produced by thioacetamide was partly reversed by the Rh(III) complex. These results are discussed in relation to the tumour-promoting effects of thioacetamide and the antitumoural action of the Rh(III) complex. PMID- 2874814 TI - Different induction of microsomal carboxylesterases, palmitoyl-CoA hydrolase and acyl-L-carnitine hydrolase in rat liver after treatment with clofibrate. AB - The levels of hepatic carboxylesterases, including palmitoyl-CoA hydrolase and decanoyl-D,L-carnitine hydrolase, were studied in total homogenates and subcellular fractions prepared from the livers of male rats fed diets containing 0.3% clofibrate. The microsomal carboxylesterase as well as the fatty acyl thioesterase are differently induced by clofibrate feeding. The specific activities of acetanilide carboxylesterase and decanoyl-D,L-carnitine hydrolase increased more than 3-fold in the microsomal fraction, compared to pellet-fed control animals. The microsomal activities of palmitoyl-CoA hydrolase and propanidid hydrolase were decreased by about 20 to 40% in clofibrate-treated rats. The specific clofibrate hydrolase activity remained unchanged after clofibrate administration, indicating that this microsomal carboxylesterase is not induced by its own substrate. The data suggest a different distribution of the differing carboxylesterase along the endoplasmic reticulum. PMID- 2874813 TI - Transport of beta-adrenergic antagonists in the absence of beta-adrenergic receptors in rat pituitary tumor cells. AB - We have demonstrated that the rat pituitary tumor cell line GH3 has a carrier mediated active transport system for the beta-adrenergic antagonist dihydroalprenolol (DHA). Transport of DHA in GH3 was saturable, with an apparent Km of 1.4 microM, was temperature and pH dependent, and was inhibited by the ionophore monensin and the amine transport inhibitor reserpine. Propranolol competed for DHA transport, but not in a stereoselective fashion. The tricyclic antidepressant imipramine also competed for DHA transport, but catecholamines or serotonin did not. This amine transport system in GH3 cells appeared to be identical to the one we recently described in several other cell types; however, analysis in those cells was complicated by the fact that they contain beta adrenergic receptors which bind beta-adrenergic ligands. In this report we show that GH3 cells do not possess detectable beta-adrenergic receptors, based on their inability to bind the partial agonist CGP-12177, their inability to bind nanomolar concentrations of DHA in a saturable, stereospecific manner, and their failure to produce cAMP in response to stimulation by beta-adrenergic agonists. Characterization of the amine transport system in GH3 cells clearly distinguishes it from receptor-mediated phenomena and should facilitate our efforts to fully understand its mechanism and significance. PMID- 2874815 TI - [Racemation of the benzodiazepines camazepam and ketazolam and receptor binding of enantiomers]. AB - The chiral benzodiazepines camazepam (1) and ketazolam (2) were resolved into the enantiomers by chromatography on the optically active adsorbent poly[(S)-N-(1 cyclohexylethyl)-methacrylamide] and fractional crystallisation or repeated chromatography, respectively. The IC50 values of the isomers and of the racemates of both compounds were determined by displacement of radioactively labelled 3H flunitrazepam and 3H-propyl-beta-carboline-carboxylate from their specific binding sites. (+)-Camazepam exhibits 14fold higher affinity compared to the (-) enantiomer. In contrast only slight differences in the receptor affinity are observed with the ketazolam enantiomers. PMID- 2874816 TI - Crystallographic and conformational studies on histamine H1-receptor antagonists. IV. On the stereochemical vector of antihistaminic activity. AB - The geometries of 14 histamine H1-receptor antagonists have been compared with the aim of finding out a common stereochemical vector of antihistaminic activity. The results obtained from X-ray crystallographic data have been compared with those obtained by minimizing the conformational energy of the molecules according to a simplified model of force field. Both approaches agree in indicating unique stereochemical requirements for optimum H1-antihistaminic activity. PMID- 2874817 TI - Enzymes of catecholamine metabolism in the brains of rat strains differing in their preference for or tolerance of ethanol. AB - The activities of the catecholamine-synthesizing and inactivating enzymes were determined in whole brains of two pairs of rat strains differing in their genetically-determined behavioural responses to ethanol. The alcohol-tolerant (AT) rats did not show any significant differences in enzyme activities when compared with the non-tolerant (ANT) strain. The activity of tyrosine hydroxylase was found to be significantly higher in brains of the alcohol-preferring (AA) rats, than in those of the alcohol-non-preferring (ANA) strain. PMID- 2874818 TI - An immobilized bienzyme system for assay of sialic acid. AB - Sialic acid has been assayed enzymatically by an immobilized two-enzyme system. The method includes cleavage of sialic acid to pyruvic acid by N-acetylneuraminic acid (NANA) aldolase and reduction of pyruvic acid by lactate dehydrogenase in the presence of NADH, which is followed photometrically at 349 nm. For the membrane preparation 5 units of lactate dehydrogenase and 1 unit of NANA-aldolase were used. The pH optimum of the reaction using potassium phosphate buffer was 7.0. This two-enzyme membrane remains 100% active for several weeks at 4 degrees C in the assay buffer and remains stable after performing experiments at 45 degrees C. PMID- 2874820 TI - Monoamines and alcohol. PMID- 2874819 TI - Somatostatin (somatostatinlike) immunoreactive cells in the human inner ear. AB - Certain epithelia of the human inner ear and human endolymphatic sac display somatostatin and/or somatostatin-like immunoreactivity. Histologic sections from 13 human temporal bones and from 15 endolymphatic sacs were studied using the unlabeled antibody peroxidase-antiperoxidase technique. The somatostatin and/or somatostatin-like immunoreactive cells were located exclusively in the covering epithelium of the spiral prominence and in the epithelium of the intermediate and rugosal part of the endolymphatic sac. In the epithelium of the spiral prominence and endolymphatic sac, secretory granules of the same size and appearance as those of intestinal or pancreatic somatostatin-producing cells were demonstrated ultrastructurally. The findings are consistent with a local exocrine, paracrine, and/or endocrine system of the inner ear. PMID- 2874821 TI - Felodipine vs hydralazine: a controlled trial as third line therapy in hypertension. Cooperative Study Group. AB - In a placebo-controlled, double-blind, randomized, parallel group study one hundred and one patients with supine diastolic blood pressure greater than or equal to 100 mm Hg phase V, despite treatment with atenolol 100 mg plus chlorthalidone 25 mg once daily also received either felodipine 5-20 mg twice daily or hydralazine 25-100 mg twice daily for 6 weeks. Felodipine achieved a lower supine blood pressure (mean +/- s.d. 177/108 +/- 29/8-138/82 +/- 19/8 mm Hg) than hydralazine (174/109 +/- 25/8-149/92 +/- 26/11 mm Hg), (P less than 0.05/P less than 0.001). Felodipine also lowered supine diastolic blood pressure to less than 90 mm Hg more often than hydralazine (42 vs 22 patients, P less than 0.001). The incidence of unwanted effects was similar in both groups. The felodipine treated patients experienced more ankle swelling and flushing than those in the hydralazine group who experienced more headache and minor gastro intestinal upset. PMID- 2874822 TI - Zopiclone produces effects on human performance similar to flurazepam, lormetazepam and triazolam. AB - The cognitive function and psychomotor performance of 10 healthy male volunteers were measured following single oral doses of: zopiclone (7.5 mg), flurazepam (15 mg), lormetazepam (1 mg), triazolam (0.25 mg) and placebo. The performance tests selected (stroop task, five choice serial reaction time, memory span, logical reasoning, mood and saccadic eye movement analysis) were thought to reflect aspects of normal daily activity. The tests demonstrated a clear reduction of performance for all active treatments. No drug emerged as the most potent sedative overall, as each of the tests was affected to a different degree by each drug. Drug effects were not qualitatively different between active treatments so that zopiclone was indistinguishable from the three benzodiazepines with which it was compared. PMID- 2874823 TI - Inhibition of human gastric secretion by ICI 162,846--a new histamine H2-receptor antagonist. AB - The inhibitory effect of ICI 162,846, a new histamine H2-receptor antagonist, on gastric secretion of acid and pepsin was studied in 10 healthy male volunteers, aged 21-30 years. Single doses of 0.5, 1.0, 2.5 and 5.0 mg were given orally at 18:00 h. Overnight 12 h gastric secretion of acid was reduced by 69, 81, 91 and 95%, respectively. The inhibition of nocturnal output of pepsin was less than acid, with median decreases of 21, 42, 73 and 87%, respectively, of the output after administration of placebo. Intragastric concentration of acid, and values of intragastric pH, during the following 12 h of the day were not significantly affected by any of the doses of the drug. We conclude that ICI 162,846 is a powerful inhibitor of gastric secretion, with potential for use in the treatment of peptic diseases. PMID- 2874824 TI - Exercise-induced hand tremor: a possible test for beta 2-adrenoceptor selectivity in man? AB - The effects of intravenous doses of propranolol, sotalol, timolol, atenolol and placebo on exercise-induced tachycardia and exercise-induced increases in hand tremor were assessed in four healthy volunteers. All active drugs produced significant reductions in exercise-induced tachycardia. Exercise caused consistent significant increases in hand tremor which were blocked by the three non-cardioselective drugs but not by atenolol or placebo. The blockade of exercise-induced hand tremor is suggested as a possible test for the assessment of the selectivity of beta-adrenoceptor blockade in man. PMID- 2874825 TI - Comparison of single doses of ketanserin and placebo in chronic stable angina. AB - Single doses of ketanserin (20 or 40 mg) and placebo were compared in a double blind cross-over study in 10 patients with chronic stable angina treated with a beta-adrenoceptor antagonist. Ketanserin had no significant effect on the exercise time to angina, the rate of ST segment depression, or the circulatory response to exercise. The 95% confidence limits indicate that ketanserin is unlikely to increase exercise time to angina by more than 20%. PMID- 2874826 TI - Inhibitory effects of neuroleptics on debrisoquine oxidation in man. AB - Liver oxidative metabolism, assessed by debrisoquine hydroxylation test, was studied in 107 healthy volunteers and in 71 patients with or without neuroleptic drug treatment. The mean metabolic ratio (MR = debrisoquine/4-hydroxydebrisoquine excretion in the urine) was 2.8 +/- 0.1 (s.e. mean) in the control group, six persons being poor metabolizers of debrisoquine (MR greater than or equal to 12.6). The mean MR (12.1 +/- 1.5) was significantly higher in those 42 patients taking neuroleptics than in patients without neuroleptics (0.8 +/- 0.1). In the former group, seventeen patients had a MR exceeding 12.6. Oral contraceptives, antiepileptics, benzodiazepines and progestin derivates did not increase MR values, the highest individual ratio being 2.72 in those subjects not receiving neuroleptics. These results suggest a probable competitive inhibition of oxidative metabolism by neuroleptics. This is a phenomenon of potential clinical importance both in patients with an inherited poor metabolic capacity and in patients receiving other drugs like beta-adrenoceptor blocking agents and tricyclic antidepressants oxidized by the same enzyme system. PMID- 2874827 TI - cGMP levels in chronic cadmium disease and osteoarthritis. AB - To investigate the effect of cadmium on guanyl cyclase activity, urine levels of the nucleotide cGMP were measured in patients with bone and renal lesions resulting from chronic cadmium exposure, in patients with osteoarthritis and in a normal age-matched control population. The effects of cadmium, zinc and mercury salts on blood mononuclear cell cGMP production were also studied in vitro. The two patient groups exhibited clear differences in cGMP excretion. Lower urine cGMP (59%, P less than 0.01) and creatinine values (43%, P less than 0.01) were found in cadmium-exposed patients and higher cGMP values (56%, P less than 0.05) in patients with osteoarthritis, compared to the control group. Creatinine adjusted cGMP values were also lower in cadmium-exposed patients (28%, P less than 0.05) and higher in patients with osteoarthritis (130%, P less than 0.01). In vitro, a 10 h exposure of mononuclear cells to cadmium or mercury salts depressed guanyl cyclase activity in most experiments. At 10(-4) M, mercury was consistently more inhibitory in all cultures (95%, P less than 0.01). As cadmium has a potential for inhibiting guanyl cyclase activity in human tissue, the low urine cGMP values found in patients with cadmium disease may be attributable to chronic cadmium exposure. High guanyl cyclase activity in patients with osteoarthritis may be associated with inflammation. PMID- 2874828 TI - Chloroplast coupling factor 1: dependence of rotational correlation time on polypeptide composition. AB - Time-resolved fluorescence depolarization measurements were made on chloroplast coupling factor 1 (CF1) labeled with pyrenylmaleimide. Rotational correlation times were determined for native CF1, for CF1 lacking epsilon and/or delta polypeptides, and for activated enzyme. The rotational correlation time measured is characteristic of the rotation of the entire enzyme. Removal of the delta polypeptide resulted in a 25% smaller rotational correlation time, although the delta polypeptide contributes less than 5% of the mass of CF1. Removal of the epsilon polypeptide was without effect. Simultaneous removal of delta and epsilon polypeptides produced a 30% smaller rotational correlation time. Activation of CF1 ATPase by incubation with dithiothreitol reduced the rotational correlation time by 15% relative to that of the latent enzyme. The rotational correlation time of CF1 with delta and epsilon polypeptides removed is essentially that expected for a spherical molecule, whereas the other forms of the enzyme can be approximated as ellipsoids of revolution; the axial ratio of the latent enzyme is estimated from the rotational correlation time and the intrinsic viscosity. These data indicate that the delta polypeptide significantly alters the shape of the enzyme and that a conformational change accompanies dithiothreitol activation of the enzyme. PMID- 2874829 TI - Interactions of Neurospora crassa plasma membrane H+-ATPase with N (ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline. AB - The carboxyl group activating reagent N-(ethoxycarbonyl)-2-ethoxy-1,2 dihydroquinoline (EEDQ) interacts with the Neurospora plasma membrane H+-ATPase in at least three different ways. This reagent irreversibly inhibits ATP hydrolysis with kinetics that are pseudo-first-order at several concentrations of EEDQ, and an appropriate transform of these data suggests that 1 mol of EEDQ inactivates 1 mol of the H+-ATPase. Inhibition probably involves activation of an ATPase carboxyl group followed by a nucleophilic attack by a vicinal nucleophilic functional group in the ATPase polypeptide chain, resulting in an intramolecular cross-link. The enzyme is protected against EEDQ inhibition by MgATP in the presence of vanadate, a combination of ligands that has previously been shown to "lock" the H+-ATPase in a conformation that presumably resembles the transition states of the enzyme phosphorylation and dephosphorylation reactions, but is not protected by the substrate analogue MgADP, which is consistent with the notion that one or both of the residues involved in the EEDQ-dependent inhibitory intramolecular cross-linking reaction normally participate in the transfer of the gamma-phosphoryl group of ATP, or are near those that do. The ATPase is also labeled by the exogenous nucleophile [14C]glycine ethyl ester in an EEDQ dependent reaction, and the labeling is diminished in the presence of MgATP plus vanadate. However, peptide maps of [14C]glycine ethyl ester labeled ATPase demonstrate that the labeling is not related to the EEDQ inhibition reaction in any simple way.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2874830 TI - Role of phosphate on the ADP-induced hysteretic inhibition of mitochondrial adenosine 5'-triphosphatase. Effects of the natural protein inhibitor. AB - Preincubation of F1-ATPase with ADP and Mg2+ leads to ADP binding at regulatory site inducing a hysteretic inhibition of ATP hydrolysis, i.e., an inhibition that slowly develops after Mg-ATP addition (Di Pietro, A., Penin, F., Godinot, C. and Gautheron, D.C. (1980) Biochemistry 19, 5671-5678). It is shown here that inorganic phosphate (Pi) together with ADP during preincubation abolishes the time-dependence of the inhibition after the addition of the substrate Mg-ATP. This preincubation in the presence of both Pi and ADP slowly leads to a conformation of the enzyme immediately inhibited after the addition of the substrate Mg-ATP. The Pi effect is half-maximal at 35 microM and pH 6.6, whereas a limited effect is induced at pH 8.0. The preincubation of F1-ATPase with Pi and ADP must last long enough (t1/2 = 5 min). The effects can be correlated to the amount of Pi bound to the enzyme, 1 mol Pi per mol (apparent KD of 33 microM) at saturation. Pi neither modifies the ADP binding nor the final level of the concomitant inhibition. When Pi is not present in the preincubation, the final stable rate of ADP-induced hysteretic inhibition is always reached when a near constant amount of Pi has been generated during Mg-ATP hydrolysis. Kinetic experiments indicate that preincubation with ADP and Pi decreases both Vmax and Km which would favor a conformational change of the enzyme. Taking into account the Pi effects, a more precise model of hysteretic inhibition is proposed. The natural protein inhibitor IF1 efficiently prevents the binding of Pi produced by ATP hydrolysis indicating that the hysteretic inhibition and the IF1-dependent inhibition obey different mechanisms. PMID- 2874831 TI - Relationship between anemia and cholesterol metabolism in 'sex-linked anemic' (gene symbol, sla) mouse. AB - The relationship between hypocholesterolemia and anemia has been recognized in humans. However, no metabolic studies in humans have been reported, nor has an animal model been developed to investigate the effects of anemia on cholesterol metabolism. We have identified an animal model, the 'sex-linked anemic' (gene symbol, sla) mouse, characterized by iron deficiency anemia, to study the relationship between anemia and cholesterol metabolism. Results from our studies showed that the serum cholesterol was significantly lower in anemic male SLA mice compared to non-anemic littermates. The lower serum cholesterol observed in anemic SLA mice was related to a decreased in vivo hepatic cholesterol synthesis. However, the decreased hepatic cholesterol synthesis in anemic SLA mice was not due to a block at the primary regulatory site, the hydroxymethylglutaryl-CoA reductase, nor at one of the secondary regulatory sites: the acetoacetyl-CoA thiolase and hydroxymethylglutaryl-CoA synthase. PMID- 2874832 TI - Inhibition of platelet factor XIIIa-catalyzed reactions by calmodulin. AB - Calmodulin was found to exhibit an inhibitory effect on platelet factor XIIIa catalyzed incorporation of pseudodonor amines into dimethylcasein, platelet actin and myosin. The inhibitory action of calmodulin on the calcium-dependent enzyme reactions was analogous to the effects of EGTA and parvalbumin on these reactions. The extent of inhibition of factor XIIIa activity was a function of calmodulin concentration when factor XIII and Ca2+ concentrations were held constant. These results indicate that calmodulin inhibits platelet factor XIIIa catalyzed reactions by sequestering calcium. PMID- 2874833 TI - Secretion of lysyl oxidase by cultured human skin fibroblasts and effects of monensin, nigericin, tunicamycin and colchicine. AB - Lysyl oxidase is an extracellular enzyme that initiates crosslink formation in the major connective tissue proteins, the collagens and elastin. This enzyme activity accumulated in a fresh medium of cultured human skin fibroblasts for at least 24 h, but the accumulation was distinctly non-linear after the first 12 h. Most of the total enzyme activity was present in the medium, the activity found in the cell layer representing about 30% of the total activity at 4 h, and about 10-15% at 24 h. The bulk of the cell-layer-associated activity appeared to be extracellular, as more than half was lost upon trypsinization. Culturing of the cells for 8 h in the presence of either monensin or nigericin, ionophores known to inhibit the secretion of many proteins at the level of the Golgi complex, markedly reduced the accumulation of lysyl oxidase activity in the medium. Monensin was particularly effective, as it produced a distinct inhibition even at a 10 nM concentration, reaching 50% at 30 nM. Both ionophores also reduced enzyme activity in the cell layer, whereas no definite decrease was seen in the activity of the trypsinized cells. The effect of monensin was evidently not due to any general toxicity on the part of the drug, since even a 500 nM concentration gave no inhibition of the incorporation of [3H]leucine into total protein. Tunicamycin also reduced lysyl oxidase activity in the medium and to a lesser extent in the cell layer, but the effective dose, 1-10 micrograms/ml, also inhibited the incorporation of [3H]leucine into total protein. The reduced enzyme activity may therefore not be due to a direct effect of tunicamycin on the glycosylation of the lysyl oxidase protein itself but may be mediated through other actions of the drug. Colchicine caused no inhibition in lysyl oxidase activity secretion even at a 10 microM concentration, although it has been reported to inhibit collagen secretion at doses more than one order of magnitude lower. PMID- 2874834 TI - Calcium transport systems in the LLC-PK1 renal epithelial established cell line. AB - ATP-dependent calcium uptake was measured in membrane vesicles prepared from the renal epithelial LLC-PK1 established cell line. The relative contribution of the nonmitochondrial versus the mitochondrial calcium uptake is larger in LLC-PK1 cell homogenates than in homogenates from renal cortex. Two types of calcium pump, characterized by the formation of calcium-dependent phosphointermediates of 135 kDa and 115 kDa, were found in membrane fractions from LLC-PK1 cells. The 135 kDa calcium pump was also detected by 125I-labelled calmodulin overlay. Although the subcellular localization in LLC-PK1 cell membranes could not be unambiguously determined, it is conceivable that the 135 kDa and the 115 kDa molecules represent the plasma membrane calcium pump and the endoplasmic reticulum calcium pump respectively, in agreement with what was found for renal cortex preparations. Extravesicular sodium partially inhibits ATP-driven calcium uptake in a plasma-membrane-enriched fraction of the LLC-PK1 cells. The effect is potentiated by a vesicle inside-negative membrane potential. Although the effect is less pronounced than in renal cortex basal-lateral membranes, this observation suggests that an Na+-Ca2+ exchange mechanism is also present in LLC-PK1 cells. ATP-dependent calcium uptake in nonmitochondrial intracellular stores was investigated, using saponin-permeabilized cells. Permeabilized LLC-PK1 cells lowered the free calcium concentration in the medium to less than 0.4 microM. More than 60% of the accumulated calcium can be released by addition of inositol 1,4,5-trisphosphate. Our data indicate that the LLC-PK1 cell line can be successfully used as model system for the study of renal calcium handling. PMID- 2874835 TI - Cyclic AMP-independent stimulation of steroidogenesis in Y-1 adrenal tumor cells by antimitotic agents. AB - The stimulation of steroidogenesis by antimitotic drugs has been studied in wild type (Y-1) and cAMP-dependent protein kinase-deficient (kin-8) mouse adrenal tumor cell lines. Unlike some other cells, Y-1 cells do not increase their cAMP output upon exposure to antimitotic drugs such as colchicine, vinblastine or podophyllotoxin, which readily increase steroidogenesis. Moreover, no increase in cAMP can be detected over an extended time span. Stabilization of tubulin polymers by taxol or high concentrations of vinblastine blocks ACTH-, cholera toxin- or colchicine-stimulated steroidogenesis without major effects on cAMP levels. Colchicine and podophyllotoxin stimulate steroidogenesis in the cAMP dependent protein kinase-deficient mutant to the same degree as in the wild-type Y-1 cells, although absolute steroid yields are lower in the mutant cells. We suggest that the antimitotic agents stimulate adrenal steroidogenesis by a cAMP independent pathway that may involve facilitation of cholesterol access to the mitochondrion. PMID- 2874836 TI - The significance of mu- and delta-receptors in rat pancreatic islets for the opioid-mediated insulin release. AB - The binding and the insulinotropic effects of enkephalin analogs and of morphine were investigated in rat pancreatic islets. Binding of [3H]Met-enkephalin was saturable, specific and reversible; the rank order for inhibition competition of [3H]Met-enkephalin binding by various compounds was Met-enkephalin = D-Ala2 MePhe4, Met(0)ol enkephalin) greater than Leu-enkephalin greater than morphine with half-maximal inhibitory constants (IC50) of approx. 0.3, 0.3, 100 and greater than 100 nM, respectively. Both the natural enkephalins exerted their insulinotropic effect only at stimulatory glucose concentrations. They had a dual action; whereas insulin secretion was increased at low enkephalin concentration, this effect was reversed at higher concentrations. However, the various enkephalins exerted this effect at different concentrations; only the EC50 values (half-maximal effective concentrations) of their insulinotropic effect were in the same range as the IC50 values of inhibition of [3H]met-enkephalin binding. Cysteamine pretreatment of rats (depletion of somatostatin containing D-cells and decrease in somatostatin secretion) did not change the Met-enkephalin effect on insulin secretion. In contrast to Met-enkephalin, binding of [3H]morphine to islets was not saturable, and morphine had no effect on insulin secretion unless at unphysiologically high concentrations. The data, therefore, indicate that: mu receptors (affinity for morphine) do not play a role in rat pancreatic islets; delta-receptors (binding site for Met-enkephalin when mu-receptors are not present) mediate the insulinotropic effect of low Met-enkephalin concentrations; and the insulinotropic action of Met-enkephalin is not mediated indirectly via the paracrine effect of an inhibition of somatostatin secretion. PMID- 2874837 TI - [Use of chemical probes in the study of F1-ATPases]. AB - The purpose of the present review is to discuss in brief the use of chemical probes for the study of the structure and the function of F1-ATPases. Special focus is brought on probes that bind covalently to the proteins. PMID- 2874838 TI - Structure and function of the ATPase-ATP synthase complex of mitochondria as compared to chloroplasts and bacteria. AB - An overview of the structure and function of the mitochondrial ATPase-ATP synthase complex is presented. Attempts are made to identify the analogies and differences between mitochondrial, chloroplastic and bacterial complexes. The relatively more precise information available on the structure of the E. coli enzyme is used to try and understand the apparently more complex structure of the mitochondrial enzyme. Recent ideas on the mechanism of ATP hydrolysis and ATP synthesis will be summarized. PMID- 2874839 TI - Receptor-mediated endocytosis: the intracellular journey of transferrin and its receptor. AB - A variety of ligands and macromolecules enter cells by receptor-mediated endocytosis. Ligands bind to their receptors on the cell surface and ligand receptor complexes are localized in specialized regions of the plasma membrane called coated pits. Coated pits invaginate and give rise to intracellular coated vesicles containing ligand-receptor complexes which are thus internalized. Transferrin, a major serum glycoprotein which transports iron into cells, enters cells by this pathway. It binds to its receptor on the cell surface, transferrin receptor complexes cluster in coated pits and are internalized in coated vesicles. Coated vesicles then lose their clathrin coat and fuse with endosomes, an organelle with an internal pH of about 5-5.5. Most ligands dissociate from their receptors in endosomes and they finally end up in lysosomes where they are degraded, while their receptors remain bound to membrane structures and recycle to the cell surface. Transferrin has a different fate: in endosomes iron dissociates from transferrin but apotransferrin remains bound to its receptor because of its high affinity for the receptor at acid pH. Apotransferrin thus recycles back to the plasma membrane still bound to its receptor. When the ligand receptor complex reaches the plasma membrane or a compartment at neutral pH, apotransferrin dissociates from its receptor with a half-life of 18 s because of its low affinity for its receptor at neutral pH. The receptor is then ready for a new cycle of internalization, while apotransferrin enters the circulation, reloads iron in the appropriate organs and is ready for a new cycle of iron transport. PMID- 2874841 TI - Integrated functioning of the chloroplast coupling factor. AB - This review is focused on some functional characteristics of the chloroplast coupling factor. The structure of the enzyme and the putative role of its subunits are recalled. An attempt is made to discriminate the driving force and the activator effects of the electrochemical proton gradient. Respective roles of delta pH, delta phi, external and internal pH are discussed with regard to mechanistic implications. The hypothesis of a functional switch of the enzyme between two states with better efficiency either in ATP synthesis or in ATP hydrolysis is also examined. A brief survey is made on some problems complicating quantitative studies of energy coupling, such as localized chemiosmosis, delta pH and delta phi computations, and scalar ATPases. The main data on the enzyme activation and the energy-dependent release of tightly bound nucleotides are summarized. The arguments for and against the catalytic competence of theses nucleotides are reviewed. Lastly, some prevailing models of the catalytic mechanism are presented. The relevance of nucleotides binding change events in this process is discussed. PMID- 2874840 TI - Topological studies suggest that the pathway of the protons through F0 is provided by amino acid residues accessible from the lipid phase. AB - The structure of the F0 part of ATP synthases from E. coli and Neurospora crassa was analyzed by hydrophobic surface labeling with [125I]TID. In the E. coli F0 all three subunits were freely accessible to the reagent, suggesting that these subunits are independently integrated in the membrane. Labeled amino acid residues were identified by Edman degradation of the dicyclohexylcarbodiimide binding (DCCD) proteins from E. coli and Neurospora crassa. The very similar patterns obtained with the two homologous proteins suggested the existence of tightly packed alpha-helices. The oligomeric structure of the DCCD binding protein appeared to be very rigid since little, if any, change in the labeling pattern was observed upon addition of oligomycin or DCCD to membranes from Neurospora crassa. When membranes were pretreated with DCCD prior to the reaction with [125I]TID an additionally labeled amino acid appeared at the position of Glu 65 which binds DCCD covalently, indicating the location of this inhibitor on the outside of the oligomer. It is suggested that proton conduction occurs at the surface of the oligomer of the DCCD binding protein. Possibly this oligomer rotates against the subunit alpha or beta and thus enables proton translocation. Conserved residues in subunit alpha, probably located in the lipid bilayer, might participate in the proton translocation mechanism. PMID- 2874842 TI - Lack of correlation between plasma DOPEG and urinary MOPEG levels in depressed patients. AB - Twenty-four-hour urinary excretion of 3-methoxy,4-hydroxyphenylethyleneglycol (MOPEG) and levels of free and conjugated plasma 3,4 dihydroxyphenylethyleneglycol (DOPEG) were measured in 56 depressed patients to find a possible correlation between these two peripheral indices of cerebral noradrenergic activity. Plasma DOPEG was measured at 9:00 AM on the same day that urine was collected for the measurement of MOPEG. All depressed patients were diagnosed as having affective disorders according to DSM-III. No correlation was found between plasma free or conjugated DOPEG levels and urinary MOPEG output. This lack of correlation was found in the total sample of depressed patients (56), in 45 patients diagnosed as having major depressive episodes, and in 24 depressed patients diagnosed as major depressive with melancholia. The authors discuss the significance of this lack of correlation between two peripheral indices of central noradrenergic metabolism. PMID- 2874843 TI - Somatostatin regulation of the CRF-ACTH-cortisol axis. PMID- 2874844 TI - Beta-endorphin and somatostatin concentrations in the ventricular cerebrospinal fluid of patients with affective disorder. PMID- 2874845 TI - Effect of transglutaminase substrates and polyamines on the cellular sequestration and processing of follicle-stimulating hormone by rat Sertoli cells. AB - Transglutaminase (TGase) substrates monodansyl cadaverine (MDC, monodansyl-1,5 diaminopentane) and methylamine (MA) and polyamines (PA) were tested for their effects on the cellular processing of radioiodinated human follicle-stimulating hormone (125I-hFSH). Specifically bound 125I-hFSH that could be released from cells during 10-min incubation period with acidified (pH 3.9) Hanks balanced-salt solution was considered membrane-bound unsequestered hormone. The rate at which cells sequestered 125I-hFSH into cellular compartments resistant to acid dissociation depended on the length of time in which cells were incubated with hormone. Cells incubated with 125I-hFSH for 15, 60, and 120 min had half-lives of sequestration of 26, 55 and 67 min respectively. One hundred-micromolar MDC inhibited degradation of 125I-hFSH as measured by the presence of radioactivity in the medium that was soluble in trichloroacetic acid. The rate of sequestration was never slower than that of controls, indicating that MDC did not decrease the ability of Sertoli cells to sequester 125I-hFSH. Despite these two observations, radioactivity associated with cells (acid-resistant radioactivity) was lower in cells treated with MDC than in controls. No effect of MDC on specific binding of 125I-hFSH was observed. Similar results were observed with MA, albeit at higher levels (0.0025-0.0425 M), consistent with their relative potency to inhibit TGase activity. Polyamines, spermine, and putrescine also decreased cell-associated radioactivity despite decreasing degradation of hFSH. TGase substrates (MDC, MA, PA) prevented entry of sequestered 125I-hFSH into the degradative pathways of Sertoli cells. These data suggest that transglutamination may influence the fate of sequestered FSH in Sertoli cells but not the rate at which sequestration occurs. PMID- 2874846 TI - Scrapie-associated fibrils (SAF) purification method yields amyloid proteins from systemic and cerebral amyloidosis. AB - We identified fibrils from non-transmissible systemic and cerebral amyloidosis using the purification method of scrapie-associated fibrils (SAF). The fibrils possessed the same nature of congophilia, filamentous structures and molecular weights as amyloid fibrils, and were resistant to Proteinase K digestion. This SAF method makes for a rapid extraction from amyloid-laden tissues. The method, therefore, may purify nontransmissible amyloids alone or together with SAF proteins. PMID- 2874847 TI - [Modulating effect of angiotensin II and bradykinin on the mediator sensitivity of central neurons]. AB - Using the methods of extracellular recording of bioelectrical activity and microiontophoresis, the effect of endogenous neuropeptides (angiotensin-II and bradykinin) on the cortical neuronal sensitivity to neurotransmitters was investigated in conscious rabbits. It was found that angiotensin-II and bradykinin modified neuronal responses to neurotransmitters, increasing, decreasing and reversing their mediator sensitivity. The most prominent effect of these neuropeptides was the increase of neuronal responses to acetylcholine and noradrenaline. At the central neuronal level, endogenous neuropeptides (angiotensin-II and bradykinin) are suggested to play the role of synaptic polytransmitter neuromodulators. PMID- 2874848 TI - [Suppressor hyperactivity in relation to allogeneic lymphocyte proliferation as a manifestation of T- T-cell interaction defects in systemic lupus erythematosus]. AB - Phytohemagglutinin-stimulated lymphocyte proliferation by con A-induced immunoregulatory cells has been estimated in patients with active systemic lupus erythematosus (SLE) treated with prednisolone. Using the combination of normal immunoregulatory cells and proliferating target cells from normal donors with immunoregulatory cells and target cells from SLE patients, it was shown that the response to immunoregulatory cells in target cells of SLE patients was impaired. This is confirmed by a slight inhibition of SLE target cell proliferation and the activating effect of immunoregulatory cells on the proliferation of "sick" targets. The data give evidence of impaired T-T-cell interaction that may be a possible mechanism of immunoregulatory defects in SLE. These disturbances can, probably, cause hyperreactivity of suppressor cells affecting normal lymphocyte proliferation. It was shown that theophylline was useful for the correction of these disorders. PMID- 2874850 TI - Red cell morphology in alcoholics: a new test for alcohol abuse. AB - Scanning electron microscopy has shown that the blood of alcoholics contains a large number of morphologically abnormal red cells. In two groups of alcoholics, the number of morphologically abnormal red cells ranged from 23.1% to 89.3% and 27.4% to 57.3% of total red cells compared to values in healthy controls of 4.5% 12.6% and 27.7%-79.5% in nonalcoholic liver disease patients. A characteristic finding was the presence of triangulocytes: these ranged from 1.2% to 18.0% of total red cells in the alcoholics as compared to 0-0.5% in healthy controls, and 0-1.3% in patients with nonalcoholic liver disease. The presence of elevated numbers of triangulocytes in blood appears to be specific to alcohol abuse. It is not, for example, elevated in nonalcoholic liver disease. No correlation was found between the number of triangulocytes or the number of morphologically abnormal red cells in blood and either the duration of alcohol abuse or the amount of alcohol consumed. Both parameters tended, however, to return to normal values during withdrawal. The mechanism by which alcohol abuse causes the morphologic abnormalities is not known. Preliminary in vitro experiments indicate that it is unlikely to arise as an effect of alcohol on circulating red cells. Based on the data presented, the measurement of the number of triangulocytes in a blood sample, although slow and laborious, may provide a highly specific test for alcohol abuse. PMID- 2874849 TI - Autocrine growth of interleukin 2-producing leukemic cells in a patient with adult T cell leukemia. AB - Leukemic cells in the peripheral blood of a patient with adult T cell leukemia (ATL), which expressed the Tac antigen/interleukin 2 (IL2) receptor, were investigated in vitro for autocrine growth by IL 2. The cells showed spontaneous proliferation in mitogen-free medium. The spontaneous proliferation of the cells was inhibited by monoclonal anti-IL 2 or anti-Tac antibody. These cells were found to produce messenger RNA for IL 2 and secrete IL 2 during short-term culture in the same medium. Recombinant IL 2 and IL 2 secreted by the cells enhanced the proliferation of the cells in a dose-dependent manner when added to the initial culture. These findings demonstrate that an autocrine mechanism by IL 2 is involved in the proliferation of ATL cells during short-term culture. PMID- 2874851 TI - Effect of acrylamide on energy-linked functions in rat brain. PMID- 2874852 TI - Quantitative estimation of quaternary ammonium neuromuscular blocking agents in serum by direct insertion probe chemical ionization mass spectrometry. AB - A new method based on selected ion monitoring chemical ionization mass spectrometry was developed to measure the quaternary ammonium neuromuscular blocking agents, pancuronium and vecuronium, in serum. An ion-pair extraction procedure is utilized to separate the compounds of interest from biological fluids. The intensities of the ion currents produced by the bisamines formed from the drugs and the corresponding deuterated internal standards through thermolytic dequaternization are monitored. The assay shows good linearity over the range of 1-500 ng/ml. This assay has been utilized in a variety of clinical pharmacokinetic studies involving surgical pediatric, geriatric and obstetric patients requiring anesthesia. PMID- 2874853 TI - Evidence for selective transport of two brush-border glycoproteins from endoplasmic reticulum to Golgi complex in rabbit enterocytes. AB - In vivo pulse-chase labeling of rabbit jejunum loops was used in conjunction with subcellular fractionation and quantitative immunoprecipitation to compare the intracellular transport kinetics of aminopeptidase with that of a 140 kDa brush border antigen not belonging to the hydrolase class. As judged by the maturation kinetics of Asn-linked glycans, these glycoproteins were found to be transported from the endoplasmic reticulum into the Golgi apparatus at different rates (t1/2 = 25-50 min). The transport from the Golgi complex to the brush-border was rapid and seemed to occur at the same rate for both glycoproteins. In keeping with these kinetic data, the steady-state levels of aminopeptidase and the 140 kDa antigen in the Golgi complex were low, although that of aminopeptidase was significantly higher. PMID- 2874854 TI - Psychoses that mask each other: a case report. PMID- 2874855 TI - The antinociceptive action of some beta-adrenoceptor agonists in mice. AB - The antinociceptive actions of several beta-adrenoceptor agonist drugs have been studied in mice by use of a modified abdominal constriction test. All the drugs studied had high antinociceptive activity, with ID50 values in the nmol kg-1 range. (-)-Isoprenaline and (+/-)-isoxsuprine were the most potent, being about ten times more active than salbutamol, the least potent drug studied. All these drugs produced their action very rapidly and appear to act within the peritoneum. (-)-Isoprenaline had about six times the potency of the (+)-isomer. (+/-) Propranolol caused rightward shifts, usually parallel, of the dose-response curves for (-)-isoprenaline. (+)-Propranolol was more than ten times less potent than the racemic drug. Practolol also caused parallel, rightward shifts of the dose-response curves for (-)-isoprenaline, and was about twice as potent as (+/-) propranolol, whether given by subcutaneous or intraperitoneal injection. Atenolol and ICI 118551 had intermediate potencies. Propranolol, practolol and ICI 118551 were all considerably less potent in antagonizing the antinociceptive actions of fenoterol and RO363, than (-)-isoprenaline. None of these antagonist drugs showed more than a slight ability to discriminate between the beta 1- and beta 2 selective agonist drugs. No evidence was found for the involvement of opioid, dopamine, or alpha-adrenoceptors in the antinociceptive action of the beta adrenoceptor agonist drugs. Evidence for and against the involvement of beta adrenoceptors is discussed, and it is concluded that if these receptors do mediate the antinociceptive action they appear to be atypical. PMID- 2874856 TI - Calcium-dependent contractile response of arterial smooth muscle to a jellyfish toxin (pCrTX: Carybdea rastonii). AB - The purpose of the present experiments was to investigate the pharmacological mechanisms of the vasoconstriction caused by the toxin (pCrTX) which had been partially purified from the tentacles of the jellyfish Carybdea rastonii ('Andonkurage'). pCrTX (0.1 to 10 micrograms ml-1) produced a tonic contraction of rabbit aortic strips, which was nearly abolished in Ca2+-free medium and was significantly reduced by verapamil or diltiazem. pCrTX stimulated 45Ca2+-influx and this effect was markedly attenuated by verapamil. pCrTX-induced vasoconstriction was significantly attenuated by phentolamine, 6-hydroxydopamine (6-OHDA) and in low Na+-medium, but not by bretylium, guanethidine, reserpinization or tetrodotoxin (TTX). pCrTX continuously and significantly increased the 3H-efflux from [3H]-noradrenaline preloaded aortic strips and this effect was completely inhibited by pretreatment with 6-OHDA and in Ca2+-free medium, but not by phentolamine, bretylium, guanethidine or TTX. A single exposure to pCrTX for 30 min greatly reduced the contractile responses to tyramine, nicotine and transmural electrical stimulation, but not those to noradrenaline or KC1. In addition, incorporation of [3H]-noradrenaline was reduced. Pretreatments with chlorphenylamine or indomethacin failed to modify the contractile response to pCrTX. These results suggest that the pCrTX-induced vasoconstriction is caused by a presynaptic action, releasing noradrenaline from the intramural adrenergic nerve terminals, and by a postsynaptic action, which consists at least in part of stimulation of the transmembrane calcium influx. Both pre- and postsynaptic actions depend on the external calcium concentration. The data further suggest that pCrTX damages the noradrenaline uptake and/or storage mechanisms without damaging postsynaptic contractile systems. PMID- 2874857 TI - Comparison of potency of alpha 2-adrenoceptor antagonists in vitro: evidence for heterogeneity of alpha 2-adrenoceptors. AB - A comparison has been made of affinity of alpha-adrenoceptor antagonists for alpha 2 binding sites in radioligand binding assays, and functional antagonist activity at pre- and postjunctional alpha 2-adrenoceptors in various in vitro preparations. The antagonists displaced [3H]-rauwolscine from rat brain and rabbit spleen membranes but there were substantial differences in rank order and absolute potency in the two tissues. pA2 values for yohimbine, phentolamine and Wy26703 against the selective alpha 2 agonist UK-14,304 were determined in the rat left atrium, rat and rabbit vas deferens and rabbit saphenous vein preparations. The pA2 values varied substantially between the tissues, differing by two orders of magnitude in the case of Wy26703. Yohimbine was more potent in rabbit preparations while Wy26703 was markedly more potent in all the rat preparations. Yohimbine and Wy26703 were compared in the dog saphenous vein preparation where pre- and postjunctional alpha 2 antagonist activity can be compared in the same tissue. As in the rabbit preparations, yohimbine was more potent than Wy26703 at both sites but the absolute potencies were different. It is concluded that alpha 2-adrenoceptors are a heterogeneous population, different subgroups being more apparent between species rather than between tissue types or location. PMID- 2874858 TI - Functional studies on human veins after storage at--190 degrees C. AB - Human saphenous veins were immersed in foetal calf serum containing 1.8 M dimethylsulphoxide, slowly frozen to -70 degrees C and stored in liquid nitrogen (-190 degrees C). Comparative in vitro studies on helical strips from unfrozen and frozen and thawed veins revealed that after thawing of frozen stored veins the contractile force development was unchanged, and the evidence suggested that the monoamine oxidase activity was unimpaired. There was a good correlation between the pD2 values of various 5-hydroxytryptamine receptor agonists and the blocking activities of various antagonists tested against 5-hydroxytryptamine (5 HT) and noradrenaline on unfrozen and frozen and thawed veins. It is suggested that cryopreservation is a useful technique for storing human veins for pharmacological studies. PMID- 2874859 TI - Binding to serum alpha 1-acid glycoprotein and effect of beta-adrenoceptor antagonists in rats with inflammation. AB - The beta-blocking effect of 4 beta-adrenoceptor antagonists with different pharmacokinetic properties was studied after intravenous and intraportal administration to control rats and to rats with experimental inflammation. In rats with inflammation the effects of propranolol and oxprenolol, which are mainly bound to alpha 1-acid glycoprotein (alpha 1-AGP), were significantly less after intravenous administration, but not after intraportal administration. In contrast, for metoprolol and atenolol, which are only negligibly serum bound, no difference was observed between control rats and rats with inflammation for either route of administration. Total and unbound serum concentrations of propranolol were measured 20 min after intravenous and intraportal administration. After intravenous administration, in the rats with inflammation total concentrations of propranolol were more than twice, and unbound concentrations less than half those of control rats. After intraportal administration the total concentrations were 8 times, and the unbound concentrations 3 times higher in the rats with inflammation. There was a significant correlation between the beta-blocking effect and the unbound concentrations of propranolol after intravenous administration, but not after intraportal administration. The latter finding is probably because the unbound concentrations were supramaximal. PMID- 2874860 TI - Receptors for neurotransmitters in opossum oesophagus muscularis mucosa. AB - Muscularis mucosa of the distal oesophagus of the opossum contains nerves which release acetylcholine and substance P(SP)-like material on field stimulation. The release of SP-like material appeared to be inhibited by the presence of exogenous muscarinic agonists and potentiated by muscarinic antagonists. Analysis of the postjunctional receptors involved using carbachol, McNeil A-343 (McN A-343), atropine and pirenzepine suggested that the receptors were not typical M2 muscarinic receptors. The potency of agonists and antagonists were consistent with some receptor properties resembling M1-muscarinic receptors. Prejunctional receptors to opiates, adenosine, agonists at alpha 2-adrenoceptors and prostaglandins were not detected. Receptors for tachykinins were present on the muscle in this tissue, but did not resemble clearly either SP-E or SP-P type receptors. They appear to be undifferentiated since most tachykinins were of similar potency. These results suggest that not all postjunctional muscarinic receptors in intestinal smooth muscle are M2 in type. There may be a gradation of types between M1 and M2. PMID- 2874861 TI - Non-cholinergic synaptic excitation in neostriatum: pharmacological evidence for mediation by a glutamate-like transmitter. AB - We studied the synaptic pharmacology of an excitatory pathway in the neostriatum using electrophysiological techniques in tissue slices from rats. In response to single electrical stimuli, two negative, extracellular potentials (N-1 and N-2) were recorded through micropipette electrodes within 150-450 micron of the stimulating cathode. N-2 was reversibly reduced or abolished by reducing the concentration of calcium in the bathing medium, while N-1 was unaffected. Both N 1 and N-2 were reversibly abolished by the local anaesthetic procaine. Single unit, extracellular action potentials were, at times, associated with either N-1 or N-2. Intracellular recordings showed action potentials at N-2 latency arising from graded, monophasic, depolarizing potentials. Bath-applied cholinoceptor and dopamine receptor antagonists failed to reduce N-2. By contrast, antagonists of excitatory amino acid transmitters reversibly reduced or abolished N-2. gamma-D Glutamylglycine (GG), (+/-)-cis-2,3-piperidine dicarboxylic acid (PDA) and DL-2 amino-4-phosphonobutyric acid (APB) blocked N-2 with ED50S of 0.79 mM, 1.0 mM and 1.1 mM, respectively. (-)-Baclofen reversibly blocked N-2 with an ED50 of 0.79 microM; (+)-baclofen was 330 times less potent. The results suggest that N-1 results from direct activation of fibre tracts or cell bodies, while N-2 is a population spike mediated by excitatory synapses whose natural transmitter pharmacologically resembles glutamate. PMID- 2874863 TI - Sulphasalazine for rheumatoid arthritis: toxicity in 774 patients monitored for one to 11 years. AB - Sulphasalazine is being used increasingly to treat rheumatoid arthritis, though its long term safety profile has not been established in this condition. The incidence and nature of adverse effects occurring in 774 patients with rheumatoid arthritis treated with sulphasalazine for periods ranging from one to 11 years were therefore noted. Altogether 205 of the patients stopped treatment permanently due to an adverse effect. One hundred and fifty six (76%) of these events occurred within three months and few beyond the first year. Most events were trivial and were self limiting after withdrawal of the drug; of the potentially more serious adverse effects, 33 (66%) occurred within three months of treatment. None of the patients died or suffered lasting ill effects. It is concluded that adverse effects of treatment with sulphasalazine are generally seen within three months; though regular monitoring is desirable during that period, thereafter few worrying problems occur. PMID- 2874862 TI - Characterization of opioid receptors in the cat carotid body involved in chemosensory depression in vivo. AB - The effects of selective opioid receptor agonists and antagonists on neural discharge recorded from carotid body arterial chemoreceptors in vivo were studied in anaesthetized cats. Mean ID50 values were determined for each agonist and used to assess chemodepressant potency on intracarotid (i.c.) injection in animals artificially ventilated with air. [Met]enkephalin, [Leu]enkephalin, [D-Ala2, D Leu5]enkephalin and [D-Pen2, D-Pen5]enkephalin were more potent chemodepressants than [D-Ala2, Me-Phe4, Gly-ol5]enkephalin, dynorphin (1-8) or ethylketocyclazocine; morphiceptin (mu-agonist) was inactive. The rank order of potency was compatible with the involvement of delta-opioid receptors in opioid induced depression of chemosensory discharge. ICI 154129, a delta-opioid receptor antagonist, was used in fairly high doses and caused reversible dose-related antagonism of chemodepression induced by [Met]enkephalin. It also antagonized depression caused by single doses of [Leu]enkephalin, [D-Ala2, D-Leu5]enkephalin, [D-Ala2, Me-Phe4, Gly-ol5]enkephalin or dynorphin (1-8). ICI 174864, a more potent and selective delta-opioid receptor antagonist, also antagonized chemodepression induced by [Met]enkephalin or by the selective delta-receptor agonist [D-Pen2, D-Pen5]enkephalin. Comparison of background or 'spontaneous' chemosensory discharge during the 30 min periods immediately before and after injecting ICI 174864 (0.1-0.2 mg kg-1 i.c.) showed a significant increase in discharge in one experiment, but in four others discharge was either unaffected or decreased after the antagonist, which argues against a toxic depression of chemosensors by endogenous opioids under resting conditions in our preparation. Sensitivity of the carotid chemoreceptors to hypoxia (ventilating with 10% O2) was increased significantly after ICI 174864, which could be taken as evidence that endogenous opioids depress chemosensitivity during hypoxia. In contrast, responsiveness to hypercapnia was reduced after the antagonist, implying that endogenous opioids may potentiate chemoreceptor sensitivity during hypercapnia. The results obtained using 'selective' agonists and antagonists provide evidence that depression of chemosensory discharge caused by injected opioids involves a delta type of opioid receptor within the cat carotid body. Endogenous opioids may modulate arterial chemoreceptor sensitivity to physiological stimuli such as hypoxia and hypercapnia. PMID- 2874864 TI - Lack of antibody to HTLV-I and HIV in patients with multiple sclerosis from France and French West Indies. PMID- 2874865 TI - Release of endogenous aspartate and glutamate induced by electrical stimulation in guinea pig cerebellar slices. AB - Whether endogenous aspartate and glutamate, candidates for the excitatory neurotransmitter of cerebellar climbing and parallel fibers, are actually released from guinea pig cerebellar slices by electrical stimulation of the cerebellar white matter, was examined by means of mass fragmentography using gas chromatograph-mass spectrometer and thin layer chromatography. Both endogenous aspartate and glutamate were found to be significantly released in a Ca- and stimulus-frequency-dependent manner. Although the origin of each amino acid could not be specified in spite of pharmacological attempt to selectively block the mossy fiber-granule cell (parallel fiber) system, these results were at least in favor of the electrophysiologically and pharmacologically suggested candidacy of these amino acids for the transmitters of cerebellar climbing and parallel fibers. PMID- 2874866 TI - Effects of dynorphin1-13 on opiate binding and dopamine and GABA uptake in stroked cat brain. AB - We previously reported that the opioid peptide dynorphin1-13 improves survival chances in stroked cats. Some evidence also suggests that changes in dopamine and gamma-aminobutyric acid (GABA) uptake may be associated with stroke. In the present study, therefore, we determined binding of the opiate [3H]ethylketocyclazocine (EKC), as well as dopamine and GABA uptake in various brain regions of control, stroked and dynorphin1-13-treated stroked cats. Cats were stroked by middle cerebral artery occlusion. In the EKC binding study, the Kd of the high-affinity site of the occluded cortex was significantly increased, relative to that of both the unoccluded side and control cortex. Dynorphin1-13 treatment reversed this effect, lowering the Kd to control level. In the dopamine uptake study, the Km was decreased and Vmax was increased significantly in unoccluded cortex, compared with that in the occluded cortex or in control cortex. Again, dynorphin1-13 reversed these effects, raising the Km and lowering the Vmax. However, the Km of occluded cortex was also increased so that it became significantly higher than that of control cortex. The Km of unoccluded subcortex in stroked cats treated with dynorphin1-13 was significantly reduced compared with control. In the GABA uptake study, there was no significant change in any parameter. The change in opioid binding observed here and its reversal by dynorphin1-13 are consistent with the notion that the peptide's beneficial effect on stroke is mediated through opiate receptors. Since opioid systems in the brain are known to have association with dopaminergic ones, the change in dopamine uptake could also be the result of an opioid effect. PMID- 2874867 TI - Neuronal activities in ventrobasal complex of thalamus and in trigeminal main sensory nucleus during EEG desynchronization in anesthetized rats. AB - Activities of somatosensory relay neurons responding to orofacial mechanical stimulation were examined in the ventrobasal complex of the thalamus (VB) and in the trigeminal main sensory nucleus (MSN) during EEG desynchronization in urethane-anesthetized rats. EEG desynchronization was induced by scrotal warming in a temperature range of 35-40 degrees C. Responses of most VB neurons to receptive-field stimulation were augmented during EEG desynchronization, when compared to responses during synchronization. Spontaneous activity of VB neurons also increased with EEG desynchronization. Responses of MSN neurons to receptive field stimulation did not change appreciably when the EEG pattern was altered. If a VB neuron was induced by iontophoretic application of glutamate to fire at the same rate as seen during EEG desynchronization, a similar increased response to receptive-field stimuli was also observed. The augmented response of the VB neuron during desynchronization may thus have resulted from increased excitability of the neuron itself. PMID- 2874868 TI - Depolarizing stimuli increase tyrosine hydroxylase in the mouse locus coeruleus in culture. AB - The influence of membrane depolarization on the development and regulation of brain noradrenergic neurons was studied in explant cultures of the mouse locus coeruleus (l.c.). Exposure to the depolarizing agents veratridine or elevated K+ significantly increased the catalytic activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. The effects of veratridine were prevented by tetrodotoxin, suggesting that transmembrane Na+ influx was necessary for the rise in TH. Morphometric analysis indicated that the rise in TH activity was not accompanied by altered TH-positive cell number or cell diameter. Rather, TH fluorescence intensity increased in each neuron, suggesting that depolarization increased TH per neuron. Immunoblot and densitometric analysis indicated that depolarization did, indeed, increase TH immunoreactive protein. Moreover, depolarization elevated enzyme activity in cultured neurons expressing the normal developmental increase in TH, as well as those in which plateau levels had already been attained. We conclude that depolarization and/or Na+ influx regulates a critical transmitter macromolecule in brain neurons, as in the periphery, by altering enzyme molecule number. PMID- 2874869 TI - Excitability changes induced in the striatal dopamine-containing terminals following frontal cortex stimulation. AB - The excitability of the dopamine-containing terminal field in the striatum (St) following frontal cortex (FC) stimulation was investigated in halothane anesthetized rats. Either glutamic acid (GLU, 6.2 mM) or square pulses (a train of 25 pulses, 500-800 microA/0.3 ms: 1 Hz/20 s) were used to stimulate FC. To stimulate St monophasic square wave pulses (10-4000 microA/0.5 ms/1 Hz) were delivered. Excitability was measured by determining the threshold for antidromic activation of substantia nigra cells. Threshold was defined as the minimum current required for antidromic invasion of the cell on 100% of non-collision trials. The mean threshold current was 1029 +/- 167 microA. Following FC stimulation a significant decrease (30%) in excitability was observed in most cases (80%). No correlation between firing rate and threshold fluctuations was observed. It is concluded that FC activity decreases the excitability of the dopaminergic nigrostriatal terminal field. Whether this is a direct or an indirect effect is discussed. PMID- 2874870 TI - Non-linear kinetics of glutamyl-tRNA synthesis catalyzed by high molecular weight complexes from rat brain neuronal cells but not from glial cells. AB - High molecular weight complexes of aminoacyl-tRNA synthetases isolated from rat brain catalyze the formation of glutamyl-tRNA with an initial lag time of the order of 1 min, as previously reported for the formation of glutamyl-tRNA and glutaminyl-tRNA catalyzed by similar complexes from bovine brain (Vadeboncoeur and Lapointe, Eur. J. Biochem., 109 (1980) 581-587). To determine the type(s) of brain cell(s) where this phenomenon occurs, we have studied the kinetics of glutamyl-tRNA formation catalyzed by high molecular weight complexes of aminoacyl tRNA synthetases isolated from neuronal and from glial cells, either transformed (Neuro-2A and C6), or from primary cultures, or isolated from rat brain. The delay in the formation of glutamyl-tRNA was observed only in the case of neuronal cells isolated from rat brain, whereas a delay in the formation of glutaminyl tRNA was also seen in these cells, as well as in neuronal cells in primary culture and in synaptosomes. The kinetics of formation of aspartyl-tRNA and valyl tRNA catalyzed by high molecular weight complexes from all these cells was linear. PMID- 2874871 TI - Expression of the enkephalin precursor gene in C6 rat glioma cells: regulation by beta-adrenergic agonists and glucocorticoids. AB - Cultured C6 rat glioma cells contain mRNA coding for preproenkephalin (A), the precursor of methionine- and leucine-enkephalin. The abundance in untreated cells was determined by blot hybridization methods to be 3-6 pg per micrograms total RNA. Treatment of confluent cells for 12 h with 10 microM (-)-norepinephrine, which activates C6 adenylate cyclase, transiently elevated preproenkephalin mRNA to 3.3 and 7.7 times the control in the absence and presence of the glucocorticoid dexamethasone, respectively. Hydrocortisone and corticosterone also potentiated the effect of norepinephrine. However, glucocorticoids alone did not alter the preproenkephalin mRNA abundance. The effect of norepinephrine + dexamethasone was blocked by the beta-adrenergic antagonist propranolol but not by the alpha-adrenergic antagonist phentolamine. Forskolin, which directly activates adenylate cyclase, similarly elevated the preproenkephalin mRNA abundance; its effect was also potentiated by dexamethasone. C6 cells contain Met enkephalin-containing protein resembling proenkephalin (apparent Mr 30,000) but little Met-enkephalin, suggesting a low level of proper precursor processing. Treatment with norepinephrine + dexamethasone raised the content of proenkephalin like protein 11-fold. Thus, preproenkephalin mRNA levels in C6 cells are regulated synergistically by adenosine 3':5'-cyclic monophosphate and glucocorticoids. These results suggest modes of regulation of proenkephalin biosynthesis in normal rat enkephalinergic cells. PMID- 2874872 TI - Increased number of sympathetic neurons with unchanged target organ innervation after postnatal polyamine treatment. AB - Treatment of newborn rats with polyamines from day 2 to day 9 after birth prevented the normal reduction in the number of sympathetic neurons in the superior cervical ganglion. About 40% more neurons prevailed in the ganglion after the polyamine treatment. This increase was paralleled by a comparable developmental increase in tyrosine hydroxylase activity and a small (17%) increase in choline acetyltransferase activity in the ganglion. However, in the iris, a target organ innervated by the sympathetic neurons, tyrosine hydroxylase activity and [3H]norepinephrine uptake remained unchanged. The results indicate that the polyamine-induced increase in the number of parent neurons is not accompanied by a change in the number of functional nerve terminals in the target organ. PMID- 2874873 TI - Ontogeny of gamma-melanocyte-stimulating hormone in the brain and hypophysis of the rat: an immunohistochemical analysis. AB - The ontogeny of gamma-melanocyte stimulating hormone (gamma-MSH)-like immunoreactive (gamma-MSHI) structures in the brain and hypophysis was investigated in the rat by means of indirect immunofluorescence. gamma-MSHI neurons in the arcuate nucleus appeared at Day 13 of gestation, in the anterior hypophysis at Day 16, in the intermediate lobe at Day 18, and in the nucleus commissuralis after birth. gamma-MSHI fibers first appeared at Day 15 of gestation in the hypothalamic area and extended dorsally to reach the surface of the diencephalon. At Day 16 of gestation, another gamma-MSHI fiber bundle was found that ran laterally along the ventral surface of the diencephalon. At Day 19, immunoreactive fibers first appeared in the forebrain, diencephalon, midbrain and upper pons, and thereafter they increased in number, reaching a maximum at postnatal Day 15. gamma-MSHI fibers in the lower pons and medulla oblongata first appeared after birth. They also increased in number with age and reached a maximum at postnatal Day 15. The present ontogenetical study has demonstrated the different times of first appearance of each of the 3 major gamma-MSHI structures containing cell groups in the brain, i.e., the arcuate nucleus, hypophysis and nucleus commissuralis. These findings may reflect the different functions of 3 groups of cells. PMID- 2874874 TI - The hypothalamic arcuate nucleus-median eminence complex: immunohistochemistry of transmitters, peptides and DARPP-32 with special reference to coexistence in dopamine neurons. AB - In this paper, we describe the results of a series of experiments which have examined the distribution within the arcuate nucleus of the hypothalamus of neurons containing the following immunoreactivities: TH-LI, GAD-LI, NT-LI, GAL LI, GRF-LI, Met-ENK-LI, Leu-ENK-LI, Met-ENK-7-LI, Met-ENK-8-LI, metorphamide-LI, DYN-LI, NPY-LI, SOM-LI, FMRFamide-LI, and CLIP-LI and ependymal tanycytes containing DARPP-32-LI. Using elution-restaining and double antibody staining techniques we have established numerous patterns of coexistence of these various neurotransmitters and neuropeptides. Thus, neurons containing TH-LI were, in some instances, also found to contain GAD-LI, NT-LI, GAL-LI, GRF-LI, Met-ENK-8-LI, Leu ENK-LI, or DYN-LI or combinations of these compounds. For example, some TH-IR neurons also contained GAL-LI and GRF-LI, while other TH-IR. neurons were also seen to contain GRF- and NT-LI. These neurons may, in fact, contain even more compounds. NPY-IR neurons and those containing SOM-LI and CLIP-LI were distinct and separate from those containing TH-LI. The distribution of these different neurochemical types of neurons and their patterns of coexistence are summarized in Fig. 34, while the relative distribution patterns of immunoreactive fibres in the median eminence are summarized in Fig. 35. PMID- 2874875 TI - The laminar distributions and postnatal development of neurotransmitter and neuromodulator receptors in cat visual cortex. AB - We review efforts to further understand the development and nature of sensory processing mechanisms in the cat visual cortex. In vitro autoradiographic and homogenate assay techniques have been employed to determine the laminar distribution and characteristics of various neurotransmitter and neuromodulator receptor populations during postnatal development. Each receptor population shows a distinct laminar-specific pattern of binding, which, in most cases, is age dependent. Changes in receptor number and affinity are also observed during postnatal development. These findings indicate that major alterations in the basic chemical circuitry of cat visual cortex are a normal feature of postnatal maturation and may play a role in plasticity mechanisms. PMID- 2874876 TI - Primary glial cells and brain fibroblasts: interactions in culture. AB - Primary glial-enriched cultures were prepared from newborn mouse cerebral hemispheres. The cultures were grown in Dulbecco's Modified Eagle Medium in which L-valine was substituted with D-valine; this medium selectively inhibits the growth of fibroblasts. Using glutamine synthetase and glial fibrillary acidic protein as immunocytochemical markers, cultures in D-valine medium were characterized as being over 80% astrocytic. However, these cultures exhibited a suppressed growth rate and lagged behind in their differentiation as assessed biochemically using DNA content and glutamine synthetase activity as markers for growth and differentiation. Growth was restored when D-valine cultures were grown in medium containing conditioned medium derived from brain fibroblast cultures when grown on matrix or killed substrata derived from brain fibroblast cultures. This in vitro approach offers the possibility of purifying factors and developing immunological probes to investigate the possible role of brain fibroblasts in influencing glial cell function. PMID- 2874877 TI - Parasitic skin diseases. AB - In this discussion of parasitic skin diseases of horses, details on life cycles are given to aid the understanding and development of control strategies. PMID- 2874878 TI - Experimental production of hemorrhagic enterotoxemia by Clostridium perfringens type C in maturing lambs. AB - Maturing lambs, eight to nine months old, were dosed by the intraduodenal route with various preparations of Clostridium perfringens type C. Whole cultures of this organism or cells suspended in fresh medium, both supplemented with soybean flour as a protease inhibitor, produced acute fatal hemorrhagic enterotoxemia in these animals. The latter preparation was more effective than the former in causing disease. Without the soybean supplement the inocula did not produce fatal disease. Dosing with toxic cell-free culture supernatant fluid, with or without soybean supplement, had no lethal effect. Animals that died showed severe hemorrhagic enteritis with necrosis and sloughing of the mucosal epithelium, involving jejunum, ileum and part of duodenum. These lesions were similar to those seen in natural cases of hemorrhagic enterotoxemia in neonatal animals. This experiment demonstrated that nonimmune animals are normally protected against C. perfringens type C enterotoxemia by adequate levels of pancreatic proteases in the intestine, and that factors which inhibit or reduce these enzymes predispose animals for the development of this disease. PMID- 2874879 TI - Restraining the elderly patient. AB - The use of chemical and mechanical restraints to control the behavior of cognitively impaired elderly patients is controversial. The issue frequently arises in nonpsychiatric as well as psychiatric hospital and chronic care settings. The lack of specific judicial and legislative mandates has left the decision to use restraints in the hands of hospital and nursing home administrators and medical personnel. Attention to the proven risks and potential benefits of restraints in the elderly patient may help to limit unnecessary application of these devices. PMID- 2874880 TI - Canadian Nurses Association. Annual meeting and biennial convention Regina, Saskatchewan, June 22-25, 1986. PMID- 2874881 TI - Quazepam, a sedative-hypnotic selective for the benzodiazepine type 1 receptor: autoradiographic localization in rat and human brain. PMID- 2874882 TI - Management of supraventricular tachycardias. PMID- 2874883 TI - Clinical pharmacology of antiarrhythmic agents. PMID- 2874884 TI - Rationale of combination antiarrhythmic drug therapy. AB - In summary, antiarrhythmic combinations have been explored as a matter of clinical necessity in many instances, and clinical circumstance has led to attempted combination therapy with two, and sometimes more, drugs. Few controlled studies using a specific combination have been performed. Therapy is thus usually empiric, based on available clinical, electrophysiologic and pharmacologic information. Nonetheless, certain general impressions are available, which may form the basis for clinical decisions and for structuring future trials (Table 6). Although single-drug antiarrhythmic therapy continues to be advisable, in certain instances combined-drug therapy may be appropriate and efficacious. The importance of potential adverse drug interactions must also be appreciated. PMID- 2874886 TI - [Sero-types in the hemorrhagic fever renal syndrome: I. An identification of sero types of HFRS by hemagglutination inhibition assay]. PMID- 2874885 TI - Differential immunocytochemical staining for glial fibrillary acidic (GFA) protein, S-100 protein and glutamine synthetase in the rat subcommissural organ, nonspecialized ventricular ependyma and adjacent neuropil. AB - Antibodies raised against glial fibrillary acidic protein (GFA), S-100 protein (S100) and glutamine synthetase (GS) are currently used as glial markers. The distribution of GFA, S100 and GS in the ependyma of the rat subcommissural organ (SCO), as well as in the adjacent nonspecialized ventricular ependyma and neuropil of the periaqueductal grey matter, was studied by use of the immunocytochemical peroxidase-antiperoxidase technique. In the neuropil, GFA, S100 and GS were found in glial elements, i.e., in fibrous (GFA, S100) and protoplasmic astrocytes (S100, GS). The presence of S100 in the majority of the ventricular ependymal cells and tanycytes, and the presence of GFA in a limited number of ventricular ependymal cells and tanycytes confirm the glial nature of these cells. The absence of S100, GFA and GS from the ependymocytes of the SCO, which are considered to be modified ependymal cells, suggests either a non astrocytic lineage of these cells or an extreme specialization of the SCO-cells as glycoprotein-synthesizing and secreting elements, a process that may have led to the disappearance of the glial markers. PMID- 2874887 TI - Hydrophilic anchor-deficient Thy-1 is secreted by a class E mutant T lymphoma. AB - To investigate the mechanism of glycophospholipid anchoring of the surface antigen Thy-1, we have undertaken a comparative biosynthetic study using a wild type Thy-1+ murine T lymphoma (BW5147) and a mutant T lymphoma (class E) that synthesizes Thy-1 but fails to express it on the plasma membrane. Labelling experiments with D-[2-3H]mannose demonstrate that, unlike the wild type, the mutant cells are secreting large amounts of Thy-1 and that the secreted molecules are hydrophilic. Moreover, unlike the wild type, they fail to incorporate [3H]palmitic acid into Thy-1. Both wild-type and mutant cells do incorporate labeled galactose and fucose into Thy-1. We conclude that the lack of surface expression of Thy-1 by this mutant results from the failure to add anchor components to Thy-1. PMID- 2874888 TI - Analysis of the transforming potential of the human homolog of mos. AB - The human homolog, c-moshu, of the mouse cellular mos proto-oncogene (c-mosmu) transforms NIH 3T3 cells at low efficiency. Furthermore, the c-moshu-induced foci are less distinct, and transformed cells contain a high level of human mos protein. The transforming activity of hybrid mos genes derived from human and mouse sequences reveals three domains within the coding region, as well as a negative regulatory sequence upstream from the c-moshu ORF that reduces its transforming efficiency. The mos C-terminal region, however, which contains the src-kinase homology domain, appears to have the greatest influence on transforming efficiency. The low transforming efficiency of c-moshu may provide a selective advantage to the host, but it also may indicate a reduced or modified function of mos in humans. PMID- 2874889 TI - Cutaneous sensitivity induced by immunization with irradiated Schistosoma mansoni cercariae. I. Induction, elicitation, and adoptive transfer analysis of cell mediated cutaneous sensitivity. AB - Exposure of C57BL/6 mice to highly irradiated (50 kR) cercariae of Schistosoma mansoni leads to the development of partial resistance against subsequent challenge with unattenuated cercariae. We have analyzed the cellular immune responses that occur during the afferent and efferent phases of this protective sensitization. Mice were immunized by exposure to irradiated S. mansoni cercariae. After challenge with irradiated cercariae, delayed-type (18-72 hr) cutaneous sensitivity reaction sites were rich in mononuclear cells and eosinophils. This reactivity was established by 4 days after sensitization, reached its maximum between 7 and 14 days after sensitization, and was maintained for over 20 weeks. These challenge reactions could be abrogated by treatment with either 200 mg/kg cyclophosphamide or 5 mg of hydrocortisone. Syngeneic adoptive transfer of cutaneous sensitivity was accomplished with lymphoid cells from the draining lymph nodes or spleens of mice sensitized 7-14 days previously. Negative selection studies of nylon-wool non-adherent cells from sensitized donors demonstrated that the cells responsible for transferring this eosinophil-rich, delayed-type cutaneous sensitivity to S. mansoni irradiated cercariae were Thy 1+, Lyt1+, Lyt2-, surface Ig- lymphocytes. PMID- 2874890 TI - Generation of lymphokine-activated killer (LAK) cells from tumor-infiltrating lymphocytes. AB - Culture of tumor-infiltrating lymphocytes (TIL) containing about 20% BMC2 tumor cells with recombinant human interleukin 2 (rIL-2) resulted in the diminish of tumor cells and the growth of lymphocytes. These IL-2-activated lymphocytes showed a strong cytotoxic activity against not only syngeneic tumor cells but also allogeneic tumor cells. Such broad-reactive killer cells, termed lymphokine activated killer (LAK) cells, are also inducible from spleen cells by in vitro activation with IL-2. However, LAK cells generated from TIL (TIL-LAK) showed higher cytotoxic activity against BMC2 than LAK cells generated from spleen cells (S-LAK). Furthermore, it was demonstrated that TIL-LAK cells revealed marginal cytotoxic activity against normal Con A blasts and YAC-1 cells as opposed to S LAK. Flow cytometric analysis of TIL-LAK indicated that TIL-LAK cells mainly consisted of Thy 1.2+, Ly 2+, asialo GM1+ cells. TIL-LAK cells displayed not only in vitro cytotoxicity but also in vivo anti-tumor activity. Furthermore, it was also confirmed that TIL-LAK cells could be induced in autochthonous mouse tumor systems and human gastric tumor systems. PMID- 2874891 TI - Induction of suppressor cells in vitro by Candida albicans. AB - Normal splenocytes cultured with Formalin-killed Candida albicans were shown to acquire significant suppressor cell activity in a period of 3 days. These cells were found to suppress both the phytohemagglutinin-induced mitogen response as well as the anti-sheep erythrocyte antibody response. Experiments were carried out to determine the nature of the suppressor cell population. Results showed that these cells were not susceptible to treatment with anti-Thy 1 antibody and complement. Panning experiments showed that the suppressor cells were not plastic adherent or Mac-1 antigen-positive. The suppressor cells were, however, adherent to anti-mouse immunoglobulin (F(ab')2-fragment)-coated dishes. Additional experiments showed that the suppressor cell activity was susceptible to treatment with monoclonal anti-Lyb 2.1 antibody and complement. These results suggest that the suppressor cell induced in vitro by Candida is a member of the B-lymphocyte lineage. PMID- 2874892 TI - Expression of E10 antigen on functionally distinct human T-cell subpopulations: comparison with 3A1 defined subsets. AB - Using PWM-driven immunoglobulin synthesis, we studied the regulatory effects of the peripheral blood T-lymphocyte subpopulations defined by the E10 antigen. This previously described antigen (E10) is present on 60% of TPBL, of T4+, and of T8+ cells. The helper activity on PWM-driven B-cell differentiation appears to be highly increased in E10- T cells. This higher capacity does not apparently reflect a different susceptibility to suppressor influences as comparable results were obtained when such suppressor influences are minimized either by removal of T8+ cells from E10- and E10+ T cells, or by removal of monocytes from responding B-cell populations. In contrast, the relative function of T-cell subsets defined by the related antigen 3A1 are influenced by the presence of suppressor cells. It is only in the presence of both T8+ cells and monocytes that 3A1+ cells exhibit a higher inducer effect. Our results suggest that E10 and 3A1 antigens--although showing strong distribution homologies--define different regulatory T-cell populations. PMID- 2874893 TI - Long-lived lymphocytes include lipopolysaccharide-reactive B cells. AB - We have used a new protocol of prolonged in vivo hydroxyurea (HU) administration which eliminates all cycling and short-lived cells. This treatment kills 99% of non-B non-T bone marrow cells, and it leaves in spleen and bone marrow "long lived" B- and T-cell populations which represent 33 and 59%, respectively, of the total numbers of lymphocytes found in untreated controls. The relative proportions of B and T cells in spleen or blood of HU-treated mice were practically unaffected, while an increased blood-to-marrow permeability results in markedly abnormal proportions of B and T lymphocytes in bone marrow. Mitogen reactivities of these long-lived lymphocytes recovered either in spleen or bone marrow of HU-treated animals were studied. The results show that such B cells respond perfectly well to the B-cell mitogen lipopolysaccharide, by proliferation and differentiation into Ig-secreting cells, and that T cells proliferate at nearly control levels in response to concanavalin A. This protocol of long-term HU treatment offers the possibility of studying selected long-lived lymphocyte populations, the clonal repertoires and functional properties of which can now be readily approached. PMID- 2874894 TI - The role of macrophages in B cell tolerance. I. Antigen-specific failure of Thy 1, Ly-2 negative adherent cells from tolerant mice to reconstitute immunocompetence in adherent cell deficient spleen cells. AB - T-Cell-independent B-cell tolerance to the hapten derivatives of carboxymethyl cellulose (CMC) or methyl cellulose (MC) appears to be controlled by Thy-1-, Ly-2 adherent (A) cells contained in the spleen or peritoneal fluid. Immunocompetence in nonadherent (NA) normal spleen cells could be restored in vitro by irradiated A cells from normal mice. However, NA cells reconstituted with irradiated A cells derived from hapten specifically tolerant mice failed to respond to the same hapten, but responded normally to an immunogenic challenge with another unrelated antigen. A cells that had been preincubated at 4 degrees C with hapten derivatized MC also failed to restore immunocompetence. While preincubation of unfractionated spleen cells with the tolerogen under the same conditions resulted in B-cell unresponsiveness, such treatment of NA cells failed to render B cells tolerant. Treatment of A cells from tolerant mice with the reducing agent potassium iodide (KI) in vitro restored their capacity to render cultures of NA cells immunocompetent to the relevant hapten. Moreover, treatment with KI of spleen cells from mice injected with the tolerogen was shown to render them responsive. We suggest that B-cell tolerance induced by hapten derivatives of CMC and MC is mediated by suppressive macrophages contained among A cells. Certain subpopulations of macrophages are known to exert cytotoxic effects upon target cells by the release at close range of oxidating agents. We postulate that hapten derivatized CMC and MC, through unique properties of the carrier, bind to and possibly activate macrophages rendering them specifically suppressive for hapten binding B cells. PMID- 2874895 TI - B and T lymphocytes regulated by idiotype anti-idiotype interactions inhibit delayed-type hypersensitivity to BCG in mice. AB - Mice infected subcutaneously with 2 X 10(7) CFU of Mycobacterium bovis strain BCG (BCG) were able to mount a specific DTH response, whereas mice infected intravenously with the same dose of microorganisms were not. The suppression turned out to be mediated by id+ anti-PPD B lymphocytes, which arose very early during the infectious process and induced anti-id B lymphocytes. These cells were found at Day 4 after infection and exerted their effect by activating antigen specific suppressor T lymphocytes, which affected the efferent phase of the DTH response. These results clearly indicate that the activation of a complex immunosuppressive circuit represents a mechanism by which BCG may interfere with the host's immune response already during the very early phases of infection. PMID- 2874896 TI - Effects of colcemid and taxol on microtubules and intermediate filaments in chick embryo fibroblasts. AB - Reports on how changes in microtubule (MT) distribution or polymerization affect the distribution of intermediate filaments (IFs) differ. Therefore, we have used cytoimmunofluorescence techniques and electron microscopy to systematically examine and compare the arrangements of MTs and IFs in cultures of chick embryo fibroblasts under the following conditions: at different times during the cell cycle, in the presence of Colcemid or of taxol, in the presence of both drugs in succession or simultaneously in varying ratios, and during recovery from treatment with Colcemid or taxol. We have found that depolymerization of MTs by 1 microM Colcemid resulted in the rapid formation of massive IF-cables, structures distinct from "collapsed IFs" or "juxtanuclear coils." Neither the rapid formation of IF-cables nor their dispersion during recovery required protein synthesis. Cells treated with 10 microM taxol rapidly formed MT-bundles, as well as aggregates of intertwining IFs, termed "IF-skeins." MT-bundles and IF-skeins displayed strikingly complementary distributions. This reciprocal distribution of packed MTs and IFs was also obvious in untreated anaphase and telophase cells. When 10 microM taxol and 1 microM Colcemid were applied simultaneously, the complementary distributions of MT-bundles and IF-skeins mimicked those in taxol alone. This ability of taxol to block Colcemid's effects was concentration dependent. Decreasing the taxol: Colcemid ratio allowed the depolymerization of MTs, which correlated with the formation of IF-cables. PMID- 2874897 TI - Immunohistochemical differentiation of gamma-glutamyltranspeptidase in focal lesions and in zone I of rat liver after treatment with chemical carcinogens. AB - gamma-Glutamyltranspeptidase (gamma-GT) is known to be increased in putative pre neoplastic foci but also in the periportal zone I of rat liver under a variety of circumstances not directly related to carcinogenesis. To be able to distinguish between these two instances gamma-GT was studied by enzyme determination in micro dissections obtained from the two locations and by both histochemical and immunohistochemical staining in serial sections. Altered hepatic foci and alterations in zone I were produced in three models of hepatocarcinogenesis: initiation by N-nitrosomorpholine and tumor promotion by phenobarbital, continuous administration of 2-acetylaminofluorene and continuous administration of methapyrilene hydrochloride. In micro-dissections gamma-GT activity was similarly increased in focal lesions and in zone I after feeding methapyrilene. Histochemically detectable gamma-GT, stained according to Rutenburg et al. (23), was observed both in zone I and in focal lesions. Focal lesions were also ATPase negative and UDP-glucuronyltransferase positive in all three models. gamma-GT in focal lesions could be selectively detected by immunohistochemical staining using antibodies to the rat kidney enzyme and an indirect peroxidase reaction. These findings suggest immunochemical differences between gamma-GT in focal lesions and in zone I. PMID- 2874898 TI - Immunohistochemically demonstrated glucose-6-phosphate dehydrogenase, gamma glutamyl transpeptidase, ornithine decarboxylase and glutathione S-transferase enzymes: absence of direct correlation with cell proliferation in rat liver putative pre-neoplastic lesions. AB - Comparison of binding of specific antibodies to glucose-6-phosphate dehydrogenase (G6PD), gamma-glutamyl transpeptidase (GT), ornithine decarboxylase (ODC) and the glutathione S-transferase B and P forms (GST-B, P) was made in putative pre neoplastic lesions during their induction and subsequent development using the Solt-Farber model. The earliest focal hepatocellular lesions were evident as single, or small groups of GST-P-positive hepatocytes in tissue taken at partial hepatectomy 3 weeks after initial application of diethylnitrosamine (DEN). With the onset of proliferation and increase in size the majority of the lesions expressed elevated levels of all of the enzyme proteins investigated with a correlation between strength of binding and morphology being apparent. While [3H]thymidine incorporation was limited during the period of acetylaminofluorene administration, to the hepatocytes demonstrating altered enzyme phenotype no direct link between proliferation rate within individual foci and level of G6PD expression could be discerned. Similarly, the elevated level of labelling characteristic of persisting nodular lesions at later stages also did not correlate with degree of G6PD alteration in individual cells. The results indicate that while changed enzyme phenotype appears as an ordered pattern suggestive of physiological adaptive nature, the degree of alteration is not directly related to proliferation kinetics under the rapid induction conditions characteristic of the Solt-Farber model. PMID- 2874899 TI - Absence of functioning alpha-adrenergic receptors in mature canine coronary collaterals. AB - To determine if mature coronary collateral vascular smooth muscle contains functioning alpha-adrenergic receptors, we studied 13 dogs, 6-10 months after circumflex ameroid occlusion. Regional myocardial blood flow was measured with radioactive microspheres in a blood-perfused heart preparation at constant aortic pressure (80 mm Hg). Normal zone resistance was calculated as aortic pressure divided by normal zone flow, and transcollateral resistance was calculated as aortic pressure minus circumflex pressure distal to the ameroid constrictor divided by coronary collateral flow. Flow and resistance were measured during adenosine vasodilation before and during graded doses of a constant infusion of the alpha-adrenergic agonist methoxamine (n = 6) or the alpha 2-adrenergic agonist clonidine (n = 7). In the hearts that received methoxamine, normal zone resistance increased from a control of 0.29 +/- 0.06 to 0.39 +/- 0.06 mm Hg X min/ml per 100 g (resistance units) during infusion of 10(-5)M methoxamine (p less than 0.05). In contrast transcollateral resistance averaged 0.24 +/- 0.02 resistance units under control conditions and did not change during methoxamine infusion. In the hearts that received clonidine, normal zone resistance averaged 0.24 +/- 0.03 resistance units and increased to 0.39 +/- 0.07 resistance units (p less than 0.05) with the highest dose of clonidine administered (10(-5) M). Transcollateral resistance averaged 0.17 +/- 0.03 resistance units during control conditions and did not change with clonidine infusion. In separate studies isometric tension development by the left anterior descending and coronary collateral vessels was examined in organ baths. The left anterior descending coronary artery demonstrated dose-dependent constriction to phenylephrine (peak response 22 +/- 5% of the response to 100 mM KCl). Clonidine produced weak constrictor responses in the left anterior descending coronary artery (5 +/- 2.5% maximal KCl response). In contrast, neither phenylephrine nor clonidine produced responses in mature collaterals. We also examined responses of mature collateral vessels to nonadrenergic agonists. In the vascular ring preparation the mature collaterals developed tension in the presence of KCl (2.3 +/- 0.9 g), prostaglandin F2 alpha (16 +/- 18% of the KCl responses), and vasopressin (90 +/- 30% of the KCl response). In adenosine-vasodilated hearts, pharmacologic doses of vasopressin caused a two-fold increase in transcollateral resistance. Thus, these studies performed on intact hearts and isolated vascular rings demonstrate that mature coronary collaterals do not contain functioning alpha-adrenergic receptors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2874900 TI - Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. AB - In 57 normal subjects (age 20-60 years), we analyzed the spontaneous beat-to-beat oscillation in R-R interval during control recumbent position, 90 degrees upright tilt, controlled respiration (n = 16) and acute (n = 10) and chronic (n = 12) beta-adrenergic receptor blockade. Automatic computer analysis provided the autoregressive power spectral density, as well as the number and relative power of the individual components. The power spectral density of R-R interval variability contained two major components in power, a high frequency at approximately 0.25 Hz and a low frequency at approximately 0.1 Hz, with a normalized low frequency:high frequency ratio of 3.6 +/- 0.7. With tilt, the low frequency component became largely predominant (90 +/- 1%) with a low frequency:high frequency ratio of 21 +/- 4. Acute beta-adrenergic receptor blockade (0.2 mg/kg IV propranolol) increased variance at rest and markedly blunted the increase in low frequency and low frequency:high frequency ratio induced by tilt. Chronic beta-adrenergic receptor blockade (0.6 mg/kg p.o. propranolol, t.i.d.), in addition, reduced low frequency and increased high frequency at rest, while limiting the low frequency:high frequency ratio increase produced by tilt. Controlled respiration produced at rest a marked increase in the high-frequency component, with a reduction of the low-frequency component and of the low frequency:high frequency ratio (0.7 +/- 0.1); during tilt, the increase in the low frequency:high frequency ratio (8.3 +/- 1.6) was significantly smaller. In seven additional subjects in whom direct high-fidelity arterial pressure was recorded, simultaneous R-R interval and arterial pressure variabilities were examined at rest and during tilt. Also, the power spectral density of arterial pressure variability contained two major components, with a relative low frequency:high frequency ratio at rest of 2.8 +/- 0.7, which became 17 +/- 5 with tilt. These power spectral density components were numerically similar to those observed in R-R variability. Thus, invasive and noninvasive studies provided similar results. More direct information on the role of cardiac sympathetic nerves on R-R and arterial pressure variabilities was derived from a group of experiments in conscious dogs before and after bilateral stellectomy. Under control conditions, high frequency was predominant and low frequency was very small or absent, owing to a predominant vagal tone. During a 9% decrease in arterial pressure obtained with IV nitroglycerin, there was a marked increase in low frequency, as a result of reflex sympathetic activation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2874901 TI - [Estimation of the transmission intensity of bancroftian filariasis in Queshan County, Henan Province]. PMID- 2874902 TI - Mexiletine therapy in patients with chronic drug-resistant malignant ventricular arrhythmias. Clinical efficacy, safety, and side effects. PMID- 2874903 TI - Improved assay of the enzymes of glutathione synthesis: gamma-glutamylcysteine synthetase and glutathione synthetase. AB - New methods for the estimation of red cell gamma-glutamylcysteine synthetase and glutathione synthetase have been developed. gamma-32P ATP is allowed to equilibrate until the gamma and beta phosphate groups are equally labelled. The amount of 32Pi released in the presence of glutamic acid and cysteine, the substrates for GC-S or in the presence of gamma-glutamylcysteine and glycine, the substrates of GSH-S, is measured. This is accomplished by extraction of the phosphomolybdate complex into isobutanol-benzene. The methods are linear with time and hemolysate concentration. Normal values are presented. PMID- 2874904 TI - A modified radioimmunoassay for arylsulfatase A in human serum and urine. AB - A radioimmunoassay was developed for the determination of arylsulfatase A (EC 3.1.6.1) in human serum and urine. An isoenzyme of arylsulfatase A purified from human urine was used as a standard antigen. The enzyme was radioiodinated with 125I using the Chloramine T method and was stable for about 4 wk. Antibody-bound enzyme was separated from free enzyme by means of a double antibody technique in the presence of polyethylene glycol (PEG). The working range of the method was 0.15-5.0 ng of arylsulfatase A per assay. The within-assay CV was about 8% for both biological fluids and the between-assay CV for serum was 14.1%. Analytical recoveries were 93.2 +/- 9.1% and 97.8 +/- 5.5% for serum and urine, respectively, and the sensitivity was 0.040 ng of arylsulfatase per assay. Serum samples of 50 healthy blood donors were assayed to establish the normal serum level of immunoreactive enzyme, which was found to be 8.3 ng/ml +/- 1.8 ng/ml of serum. Storage of frozen serum was shown to have no significant effect on results obtained using this RIA. PMID- 2874905 TI - Normal circulating immunoreactive growth hormone releasing factor (hGRF) concentrations in patients with functional hypothalamic hGRF deficiency. AB - Using a highly specific radioimmunoassay we have measured the concentrations of human growth hormone releasing factor (ir-hGRF) in the peripheral circulation of six individuals with acquired hypothalamic hGRF deficiency. Despite their hypothalamic dysfunction venous plasma ir-hGRF increased normally in every patient after the stimulus of a mixed breakfast, from an average concentration basally of 13.6 +/- 6.0 pg/ml to a maximum of 29.0 +/- 8.4 pg/ml (mean +/- SEM) at 120 min. The findings indicate that circulating hGRF is at least in large part extrahypothalamic in origin, which in turn implies a physiological role for hGRF in the periphery. PMID- 2874906 TI - Lack of effect of muscarinic cholinergic blockade on the GH responses to GRF 1-29 and TRH in acromegalic subjects. AB - It is well known that muscarinic cholinergic blockade either reduces or abolishes stimulated GH release in normal subjects. In this study we have investigated whether cholinergic muscarinic blockade could reduce the GH responses to GRF 1-29 and TRH in acromegalic subjects. Eight acromegalic subjects underwent two GRF tests (GRF 1-29, 1 microgram/kg i.v.) with and without pirenzepine (0.6 mg/kg, i.v.). A further four of these patients received TRH (200 micrograms/kg, i.v.) on separate occasions with and without pirenzepine (0.6 mg/kg, i.v.). Cholinergic muscarinic blockade did not alter the GH responses to GRF and TRH in patients with acromegaly. These findings are in contrast with previous data reported on the effects of cholinergic blockade on stimulated GH levels in normal subjects and in patients with type I diabetes mellitus and are compatible with the view that somatotroph adenomas are functionally disconnected from hypothalamic control mechanisms. PMID- 2874907 TI - Comparative evaluation of cyclic AMP and iodide accumulation responses to thyroid stimulating immunoglobulins in cultured FRTL-5 cells. AB - The rat thyroid cell strain FRTL-5 was used to investigate the relationship between cyclic AMP and iodide accumulation responses to thyroid-stimulating immunoglobulins (TSIg). Immunoglobulin G-enriched precipitates of sera from 19 of 21 (90%) newly-diagnosed Graves' disease patients gave significant (P less than 0.01) accumulation of iodide (125I), and 16 of these also stimulated intracellular cyclic AMP. Correlation was poor however, with certain TSIg preparations giving widely divergent responses. After initiation of antithyroid treatment, 40% of sera investigated contained TSIg detectable in both bioassay systems, and all but one of the remainder were stimulatory in one of the two bioassays. All patients in remission were devoid of detectable TSIg as determined by iodide accumulation, although a single preparation stimulated cyclic AMP accumulation. LATS-B, a lyophilized reference serum preparation containing high TSIg activity, enhanced iodide accumulation, which showed evidence of correlation with intracellular cyclic AMP at doses above 0.5 mU/ml. At lower doses, iodide accumulation was observed in the absence of detectable cyclic AMP accumulation. TSH and LATS-B-induced iodide accumulation were enhanced, and iodide efflux reduced, by the anion channel blocker 4-4' diisothiocyanate stilbene 2,2' disulphonic acid (DIDS). In contrast, Ig-enriched fractions of normal sera decreased both basal and stimulated iodide accumulation, but were without effect on efflux. TSIg from untreated Graves' sera gave widely-differing iodide accumulation responses which showed poor correlation with both intracellular cyclic AMP and cyclic-AMP-independent iodide efflux. This clear dissociation of responses to serum Ig preparations suggests that iodide uptake in FRTL-5 cells, which do not organify iodide, may be subject to variable effects of non-TSIg components of Graves' sera, on both iodide uptake itself, and as inhibitors of TSIg-induced accumulation of intracellular cyclic AMP. PMID- 2874908 TI - Thyroidal response to an increase or decrease of endogenous TSH in patients with hyperthyroidism and its correlation with TSH binding inhibiting immunoglobulin. AB - One hundred and twenty-one patients with hyperthyroidism of Graves' disease were treated with antithyroid drugs for 3 years and thyroidal response to an increase or decrease of TSH and the serum thyroid stimulating immunoglobulin (TSI) activity were studied in relation to the presence or absence of TSH binding inhibiting immunoglobulin (TBII). TBII activity was positive in 83% of untreated patients but decreased gradually with time during antithyroid drug therapy. Thyroidal radioactive iodine uptake (RAIU) was suppressed by T3 in 86 of 121 treated patients but 16% of suppressible patients had TBII activity. Thyroidal RAIU was not suppressed by T3 in 35 treated patients, and 19 of 35 unsuppressible patients had TBII activity but other 16 patients did not. When suppressible and unsuppressible patients were combined, suppression of serum T4 and thyroidal RAIU by T3 tended to be less in the presence of TBII activity. TSI activity was detected in the sera of untreated patients but did not correlate with TBII activity. TSI activity was undetectable after treatment for 3 years irrespective of presence or absence of TBII activity and T3-suppressibility. TSH, T4 and T3 elevation in response to 500 micrograms thyrotropin releasing hormone (TRH) was normal in all treated patients irrespective of presence or absence of TBII activity and T3-suppressibility. It is suggested that in vivo thyroidal responsiveness to an increase or decrease of endogenous TSH did not correlate with the presence or absence of TBII activity after long-term therapy with antithyroid drugs. PMID- 2874909 TI - Effects of furosemide and indapamide upon pancreatic insulin and somatostatin secretion in vitro. AB - Antihypertensive treatment with furosemide and indapamide may eventually cause impairment of glucose metabolism. To study if this was due to a direct effect on the endocrine pancreas, we examined the effects of furosemide and indapamide on the release of insulin and somatostatin from the isolated perfused pancreas of normal dogs. Furosemide at concentrations ranging between 1-30 micrograms/ml inhibited insulin in a dose-dependent manner (2p less than 0.01) whereas the somatostatin secretion was left unchanged. Also the infusion of indapamide at doses ranging between 0.05-1 micrograms/ml subdued B-cell secretion at the two highest concentrations of 0.5 (by 15 +/- 2%, p less than 0.01) and 1 microgram/ml (by 22 +/- 5%, p less than 0.02) while pancreatic D-cell secretion did not alter. The results suggest, that furosemide and indapamide possess the ability to directly inhibit insulin secretion. Whether this effect is of clinical importance for the diminution in glucose tolerance observed during therapy remains, however, uncertain. PMID- 2874911 TI - [Ototoxicity of drugs]. PMID- 2874910 TI - Safety and efficacy of antiemetics used to treat nausea and vomiting in pregnancy. AB - The safety and efficacy of antiemetic drugs used in the treatment of nausea and vomiting during pregnancy are reviewed. Confirmation of the teratogenicity of drugs in humans is difficult; the risk can be estimated from results of cohort studies and case-control studies. The possible teratogenicity of Bendectin (doxylamine succinate and pyridoxine hydrochloride) was studied thoroughly; although the risk was minimal, the drug was withdrawn from the U.S. market. Whether phenothiazines are teratogenic has still not been conclusively determined. A large number of epidemiological studies have not shown meclizine to be teratogenic in humans. More information about metoclopramide is necessary before it can be safely recommended for use during pregnancy. The risks of using dimenhydrinate and diphenhydramine appear to be low. Pyridoxine is considered safe for use during pregnancy, but its efficacy in treating nausea and vomiting has not been determined. The relative efficacy of these agents has not been determined. The available data suggest that meclizine and dimenhydrinate are the antiemetics that present the lowest risk of teratogenicity; meclizine is the drug of first choice. Phenothiazines should be reserved for treating persistent vomiting that threatens the maternal nutritional status. PMID- 2874912 TI - [Cytolytic episodes during cirrhosis]. PMID- 2874913 TI - Clinical significance of increased or decreased serum alkaline phosphatase isoenzymes. PMID- 2874914 TI - Interpretation of gamma-glutamyltransferase isoenzyme electrophoretic patterns. PMID- 2874915 TI - Incidence of a heterosis effect in adrenal responsiveness to ACTH stimulation in the chicken. AB - No differences exist between basal plasma corticosterone concentrations of broilers ferals and first generation large crossbreds (White leghorn x New Hampshire). Crossbreds show near double adrenal responsiveness to synthetic ACTH administration, indicating a heterosis effect for this characteristic. Extraction of chicken plasma with 30% aqueous polyethylene glycol solution eliminates the need for tedious and expensive pre-assay purification of plasma. PMID- 2874916 TI - Effects of cycloheximide on in vitro testosterone secretion from RANA catesbeiana ovaries. AB - A 1 hr exposure to 20 micrograms/ml of the protein synthesis inhibitor, cycloheximide (CHX), essentially abolished secretion of testosterone (T) by bullfrog ovarian fragments during simultaneous administration of homologous pituitary extract and CHX. Removal of CHX from the medium after 4 hr of treatment reversed the inhibition of T secretion, allowing it to attain control levels. Pre exposure of ovarian fragments to CHX was not required to obtain an inhibition of T secretion. These data supported the hypothesis that protein synthesis is required for acute and chronic gonadotropic stimulation of steroidogenesis by the bullfrog ovary. PMID- 2874917 TI - Electrical properties of a Na+-dependent phenylalanine transport in lizard (Lacerta galloti) duodenum. AB - The unidirectional transepithelial fluxes of L-phenylalanine across lizard duodenum were determined in flux chambers. Phenylalanine was preferentially transferred from the mucosal to the serosal fluid. This transport was accompanied by an accumulation of substrate from the mucosal medium into the tissue to a similar level and against a concentration gradient. There was no net movement of phenylalanine when the sodium was substituted by choline. The influx of L phenylalanine into the epithelial cells of lizard duodenum was examined by incubating slices of intestine in radioactively-labelled solutions of the substrate for 2 min. The steady-state uptake was assessed after similar incubations lasting 45 min. Phenylalanine influx obeys the Michaelis-Menten equation with a Km of 5.1 and is dependent on the presence of sodium ions in the incubation medium. Phenylalanine has been used to induce changes in short-circuit current (delta Isc) across intestine. delta Isc was a hyperbolic function of amino acid concentration characterized by the parameters Jm (maximum change in delta Isc) and Km (concentration needed to attain an delta Isc equal to half the Jm). delta Isc determined Km constants showed good agreement with values obtained from direct measurements of phenylalanine uptake into tissue. PMID- 2874918 TI - Hemoglobin and oxygen: different affinities in two species of rodents (Mus musculus and Pitymys duodecimcostatus). AB - Five different hemoglobins have been demonstrated by polyacrylamide-gel disk electrophoresis in the species Mus musculus. Oxygen affinities of hemoglobin (P50) from Mus musculus and Pitymys duodecimcostatus hemolysates were determined at pH 7.4 and 37 degrees C. Values obtained for delta log P50/delta pH in hemolysates from both species point out a more pronounced Bohr effect in Pitymys duodecimcostatus. PMID- 2874919 TI - Parturition in the camel (Camelus dromedarius) and some behavioral aspects of their newborn. AB - Symptoms of approaching parturition and the stage of parturition were described for eight pluriparous camels. The average time for the complete process of parturition was 373.9 +/- 38.2 min. The body weights at birth of the newborn males and females were 31.3 +/- 1.69 and 24.5 +/- 2.5 kg, respectively. Standing and first suckling by the neonatal camels occurred at 68.6 +/- 6.2 and 98.6 +/- 11.3 min, respectively. PMID- 2874920 TI - The effect of 3,5,3'-triiodo-L-thyronine on gill Na+/K+-ATPase of rainbow trout Salmo gairdneri, in fresh water. AB - Gill and liver microsomal Na+/K+-adenosine triphosphatase (ATPase) activities and plasma levels of 3,5,3'-triiodo-L-thyronine (T3) were measured in rainbow trout (100-300 g) immersed in a freshwater solution of T3 for 6 or 7 days at 11 degrees C. Ambient T3 (1.25 or 2 micrograms T3/100 ml H2O) elevated plasma T3 within a physiologic range; an ambient concentration of 10 micrograms T3/100 ml produced supranormal plasma T3 levels. All T3 treatments depressed gill ATPase to a similar degree. Liver ATPase was lower than gill ATPase and was elevated by a physiologic T3 treatment. PMID- 2874921 TI - Effect of starvation and protein-feeding on blood amino acid compartmentation of domestic fowl hatchlings. AB - The amino acid concentrations in plasma and blood cells of 5-day old domestic fowl hatchlings that received either standard feeding, protein-feeding or were starved have been determined. The effects of 5-day starvation or protein feeding did not alter significantly the combined amino acid concentration of blood plasma, but decreased blood cell levels. The patterns of individual amino acid changes observed in starvation or protein-feeding were similar in both groups when compared with those of controls. However, starvation-induced effects were actually more marked than those observed in protein-fed animals. The patterns of change with starvation of individual amino acids in the hatchling blood compartments were very different from those observed in mammals subjected to short or medium-term starvation. The mechanisms controlling circulating amino acid concentrations act in both situations studied to maintain the plasma amino acid concentrations despite marked changes in the availability of 2-amino nitrogen energy to the animal; changes in blood amino acid compartmentation buffering plasma amino acid availability. PMID- 2874922 TI - Preparation of ovine carrier erythrocytes: their action and survival. AB - Conditions for preparation of and the stability of carrier-red blood cells (C RBC) are described for sheep RBC. The average percentage entrapment of 14C sucrose was greater than 35% with 65% recovery of the cells. Cells prepared by dialysis encapsulation are morphologically similar to sheep RBC, although smaller in size than normal sheep RBC. C-RBC have a 28-day half-life in vivo and are stable in vitro for 24 hr at 37 degrees C. C-RBC are more resistant to osmotic stress than are normal sheep erythrocytes. PMID- 2874923 TI - Survival of murine carrier erythrocytes injected via peritoneum. AB - Carrier-red blood cells (C-RBC) can be administered by intraperitoneal injection (IP) in mice, and C-RBC survive in circulation as well as cells administered by intravenous injection (IV). There was no difference in the 24 hr post-injection organ distribution of normal RBC and C-RBC, an indication of the normalcy of C RBC. Approximately 25% of the C-RBC remain in circulation 14 days post-injection indicating a 20-day half-life for C-RBC in mice. This alternate injection method for RBC also allows for extravascular targeting of RBC to peritoneal macrophages. PMID- 2874924 TI - Anorectic effect of fenfluramine, cholecystokinin and neurotensin in genetically obese (ob/ob) mice. AB - To investigate the satiety defect of hyperphagic genetically obese (ob/ob) mice, acute feeding responses to three differently acting anorectic agents were determined in 7-9 weeks old lean (+/+) and ob/ob mice habituated to a restricted (0900-1230 hr) daily feeding routine. Fenfluramine (10 mg/kg), cholecystokinin (100 U/kg) and neurotensin (500 micrograms/kg), administered intraperitoneally 15 min before feeding, each produced a rapid but transient suppression of food consumption in ob/ob mice, similar to lean controls. The results suggest that neural satiety mechanisms triggered via serotoninergic pathways (fenfluramine), vagal afferents (cholecystokinin) and the hypothalamic paraventricular nucleus (neurotensin) are functional in ob/ob mice, supporting the view that the satiety defect of ob/ob mice resides outside of the nervous system. PMID- 2874925 TI - Amino acid absorption in jejunum of rats in vivo--a kinetic comparison of distal resection effects. AB - Jejunal absorption of leucine and cycloleucine by sham and 50% distal resected rats in vivo was studied by measuring the passive component and the active transport. After 5 months postresection the total amino acid absorption was increased. The mass-transfer coefficients of the passive process (obtained in presence of methionine) were higher in remnant jejunum than that in control rats, whereas the active transport remained unaltered after resection. When the kinetic constants of the saturable and non-saturable components were corrected for the unstirred water layer effects, the "real KD" increased in the resected group, whilst similar values for the "real Km and Jmax" were obtained. PMID- 2874926 TI - Transcuticular solute movement in parasitic nematodes: relationship between non polar solute transport and partition coefficient. AB - The rate constants (K) for steroid transport across the isolated cuticle of Ascaris suum were, linearly related to partition coefficients (P) of steroids in model solvents. The slope of log P vs log K for an isolated cuticle was closest to unity for the more polar solvents, octanol and ether, suggesting that the barrier to steroid movement across the cuticle has partition properties similar to these solvents. The transcuticular movement of steroids into intact adult A. suum and infective larvae of Haemonchus contortus was predicted by the P in model solvents suggesting that the same barriers for transcuticular solute movement may exist in intact worms as in isolated cuticles. PMID- 2874927 TI - Neural response mechanisms in the photoreceptive pineal organ of goldfish. AB - In order to classify the different cell types involved in signal transmission of the photoreceptive pineal organ of the goldfish, Carassius auratus, intra- and extracellular electrical responses were recorded from photoreceptors and second order neurons. Photoreceptor responses to light consisted of hyperpolarizing potentials up to 30 mV. The responses were graded with intensity and their voltage-intensity relation followed the hyperbolic function V/Vmax = In/In + sigma n. Latencies varied between 500 msec for responses near threshold and 60 msec for supersaturating flashes. The response duration increased up to 60 sec for flashes 2 log units above the saturation level. Action spectra of individual photoreceptors peaked at lambda max = 530 nm and corresponded to measurements of extracellular slow mass potentials or spike potentials. Slow mass potentials exhibited similar characteristics as intracellular recorded photoreceptor potentials with respect to latency, voltage-intensity curves and spectral sensitivity. Ganglion cells showed maintained discharges under conditions of steady illumination. The discharge rate changed inversely with the logarithm of steady illumination over a range of 8 log units. The response to light flashes was purely achromatic and consisted of inhibition of the maintained discharge. The physiological properties demonstrate that the pineal organ of the goldfish is an effective functional photoreceptor organ operating both in dim and in bright light. The light-induced hyperpolarization of photoreceptors lead to an inhibition of the nervous discharge of ganglion cells. The direct flow of information from photoreceptors to ganglion cells is the basic channel of data processing in the goldfish pineal. PMID- 2874928 TI - Changes in blood levels of nucleoside triphosphates, hemoglobin and hematocrits during parr-smolt transformation of coho salmon (Oncorhynchus kisutch). AB - Increases and subsequent decreases in gill Na+-K+ ATPase activity during parr smolt transformation in coho salmon were accompanied by changes in blood nucleoside triphosphate (NTP) levels, hemoglobin concentrations and hematocrits. An advanced photoperiod schedule accelerated the parr-smolt transformation and the rate of changes in Na+-K+ ATPase activity, NTP and hematocrit levels. Ratios of NTP:hematocrits and of NTP:hemoglobin increased during smoltification. Hematological changes suggest preparation for increased oxygen demand during migration and greater energy requirements by erythrocytes during smoltification and sea-water adaptation. PMID- 2874929 TI - Volume regulation in salt-acclimated toad (Bufo viridis): the role of urea and the urinary bladder. AB - Body water (weight) was studied in the euryhaline toad Bufo viridis during high salt (500 mOsm NaCl) acclimation. Plasma osmolality was greatly increased upon salt acclimation mainly by urea, and was always hyperosmotic to the ambient solution. Water content was regulated quite efficiently in slowly acclimated undisturbed toads. Repeatedly catheterized toads behaved like osmometers when transferred to hyperosmotic solutions. Total urea loss was greatly reduced in salt acclimated toads, suggesting urine was not voided under these conditions. It is concluded that urea accumulation, inhibition of the urine voiding response and the urine in the bladder are the principal factors involved in volume regulation under conditions of salt acclimation. PMID- 2874930 TI - Testing the hypothesis that crypt size determines the rate of enterocyte development in neonatal mice. AB - Pieces of mid-jejunum taken from 7-9 day old mice have been used to determine microvillus length in enterocytes located at different points along the crypt villus axis to test the hypothesis that enterocyte development of structure is directly determined by the physical characteristics of the intestinal crypt. Parallel measurements of enterocyte migration rate were carried out using tritiated thymidine to determine the time course of microvillus elongation in neonatal mice. Microvillus length approximately doubled during early enterocyte migration from the crypt base to the lower part of the villus. Enterocyte migration rate was only 0.9 micron/hr at this stage of development, a value considerably less than that found in adult intestine. Results plotting the time dependency of microvillus elongation were fitted by a logistic curve giving a maximal rate for microvillus growth of 0.004 micron/hr. The corresponding estimate of crypt depth was 35 microns. Both these values are considerably less than those found in adult intestine. These results provide strong support for the general hypothesis that some factor associated with the physical length of the crypt, called crypt factor or CF, is directly responsible for controlling the way enterocytes organize subsequent structural differentiation of their surface membranes. PMID- 2874931 TI - O2 and CO2 concentrations in burrows of euthermic and hibernating golden hamsters. AB - O2 and CO2 concentrations were measured in burrows of golden hamsters (Mesocricetus auratus, W.) simultaneously with body temperature. In sealed burrows of euthermic golden hamsters daily mean concentrations of 15.1 +/- 1.2% O2 and 5.7 +/- 1.2% CO2 were measured, the extreme values amounting to 10.0% O2 and 10.8% CO2. The gas composition showed a daily rhythm. During hibernation, the gas composition of the burrow changed significantly to 20.0 +/- 0.5% O2 and 1.8 +/- 0.8% CO2. PMID- 2874932 TI - Energy metabolism in largemouth bass (Micropterus floridanus salmoides) from stressed and non-stressed environments: adaptations in the secondary stress response. AB - White muscle proteins, carbohydrates, lipids, adenylates, phosphagen and the AEC, (adenylate energy charge) were measured in bass inhabiting stressful and non stressful environments. Within an environment, in June stressed bass had higher carbohydrates, while non-stressed bass had lower ATP, total adenylates and AEC. Comparisons between environments revealed: non-stressed bass had higher ATP/ADP and AEC's in May, CrP/ATP in June, and protein in July; while stressed bass had higher carbohydrate in June and lipid in July. Other metabolites varied insignificantly. AEC's of both groups were within the optimal range indicating physiological compensation (adaptation) of energy metabolism (secondary stress response) occurred in bass inhabiting the stressful environment. PMID- 2874933 TI - Efflux of 45Ca from isolated smooth muscle cells of guinea-pig taenia caeci. AB - Single smooth muscle cells were isolated from guinea-pig taenia caeci by digestion with collagenase. The 45Ca desaturation curve from isolated cells, which were previously washed with Ca2+-free solution containing EGTA in Ca2+-free modified Locke solution, consisted of three components (half-time: 1.0, 3.8 and 12.4 min). The 45Ca efflux from isolated cells in the third component was significantly increased by caffeine. This increase was suppressed by procaine, but was not affected by La3+. These results suggest that, in guinea-pig taenia caeci, there are at least four Ca2+ compartments: superficial low and high affinity bound Ca2+ and cellular low and high affinity bound Ca2+. Caffeine releases Ca2+ from the cellular high affinity binding sites. PMID- 2874934 TI - Chemical and morphological differences in the kidney zones of the elasmobranch, Raja erinacea mitch. AB - The histological investigation of the kidney of the skate Raja erinacea revealed a thin cap of dorsal bundles, which contain segments of single nephrons that are arranged separately in a countercurrent manner, and a large ventral zone, where the second proximal segments (PII) and parts of the lower nephron are located. This zonation is apparent in fresh, unfixed material and makes it possible to separate small tissue samples under a dissecting microscope. The osmolality in both zones does not differ. The dorsal bundle zone had a lower urea concentration and a higher sodium concentration than the ventral zone. The differences in the mean concentrations of the tissue samples indicate a gradient for the two substances along the bundles. Determinations of amounts of water and solutes per mg solute-free, dry tissue of the two zones, showed that the amounts of water, total osmolytes, Na and K were greater in the bundle zone than in the ventral zone, while the amount of urea was identical in the two zones. This indicates that the lower urea concentration in the bundle zone is established through an accumulation of Na and water in the interstitium. The countercurrent arrangement of very early and late segments of single renal tubules supports the concept of passive reabsorption of urea in the kidney of the marine elasmobranch. PMID- 2874935 TI - Biliary secretion in the rat after partial hepatectomy. AB - The secretory efficiency of the liver increased in rats at 12 hr after partial hepatectomy. The secretory efficiency was seen to decrease at 24 hr after partial hepatectomy and increased again at 2-4 days following liver resection. These changes would correspond to the evolution of the hepatocyte proliferative process. The secretion of bile acids expressed per 100 g of body weight had returned to normal at 16 days after partial hepatectomy, although choleresis and the secretion of inorganic electrolytes remained lowered. PMID- 2874936 TI - Physiological stress responses in big gamefish after capture: observations on plasma chemistry and blood factors. AB - The plasma electrolytes, Na+, K+, Ca2+, Cl- and osmolarities had high values in capture-stressed big gamefish. Blood metabolites measured after stress showed glucose and lactate elevations. The activity of the plasma enzymes alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatine kinase and lactate dehydrogenase suggested tissue disruptions following severe capture stress. Haematocrit values and methaemoglobin were high in capture stressed gamefish. The plasma chemistry of resting and capture-stressed snapper (Chrysophrys auratus) was studied for comparison. Specific differences in plasma biochemistry appeared to be the result of different strategies of fish behaviour during capture. PMID- 2874937 TI - A preliminary report on the effects of parasitism by the leeches Theromyzon cooperi and Placobdella garoui on the physiology of the redbilled teal Anas erythrorhyncha. AB - The effects of parasitism by leeches Theromyzon cooperi and Placobdella garoui on the redbilled teal Anas erythrorhyncha were investigated. Leeches with initial body mass ranging from 5.2 to 28.4 mg were allowed to parasitize redbilled teal clamped in Perspex containers. Theromyzon cooperi increased its body mass after parasitism with a mean of 10.5-fold compared to 6.9-fold for P. garoui. Changes were also observed in values of various haematological and biochemical variables of the redbilled teal monitored during this investigation. PMID- 2874938 TI - Changes in blood progesterone concentration during pregnancy in the lizard Tiliqua (Trachydosaurus) rugosa. AB - Progesterone concentrations during pregnancy were measured in the plasma of the viviparous lizard (scincid) Tiliqua (Trachydosaurus) rugosa, using a radioimmunoassay specific for progesterone. The length of gestation in this Australian lizard was 140-170 days. The average number of young was 2.8 and the mean neonatal weight 58 g (maternal body weight 500-700 g). The mean concentration of progesterone was greatest (7.2 nmol/l) during the second trimester of pregnancy; mean values during the first and third trimesters, and in non-pregnant females, were 1.8, 0.9 and 0.2 nmol/l respectively. PMID- 2874939 TI - Kinetics of D-glucose and L-leucine transport into sheep and pig intestinal brush border membrane vesicles. AB - The kinetic parameters (Vmax, Kt) of Na+-dependent D-glucose transport into brush border membrane vesicles (BBMV) from sheep and pig jejunum were determined. Due to the fermentation of ingested carbohydrates in the rumen the small intestine of ruminants (sheep) has to absorb much less glucose than the small intestine of monogastric omnivores (pigs) or herbivores. Kinetic analysis of the concentration dependence of D-glucose transport revealed a ten-fold smaller Vmax value combined with a five times lower Kt value in sheep BBMV compared with pig BBMV. The Vmax value for L-leucine transport did not differ between the two species investigated, whereas the Kt value in the sheep exceeded that in the pig. It is concluded from these results that the mechanism for Na+-dependent D-glucose transport in ruminants is adapted to the small amounts of carbohydrates reaching the small intestine. PMID- 2874940 TI - A comparison of the differential accumulation of cadmium in the tissues of three species of freshwater fish, Salmo gairdneri, Rutilus rutilus and Noemacheilus barbatulus. AB - Roach and stone loach were exposed to cadmium dissolved in their aquarium water at 500 and 1250 micrograms/l, respectively, and the distribution of the metal accumulated in the major body organs was determined. The pattern of distribution for each species was somewhat different and was distinct in each case from that observed previously with rainbow trout. The total body loads of cadmium accumulated by the three species were assessed during the period of exposure and found not to correlate directly with the concentration of cadmium to which the individual species had been exposed. An alternative comparator was devised which as the quotient of the total body cadmium accumulation (microgram/100 g body wt) and the notional cadmium dose (microgram/l) X weeks was described as a fractional retention coefficient for cadmium. The coefficient was constant for each species at different periods of exposure to cadmium alone. The values of the coefficient for roach and stone loach were however much lower than that for rainbow trout. When rainbow trout were preexposed to zinc (100 micrograms/l, 5 days) before being exposed to cadmium, the fractional retention coefficient for cadmium fell to a value similar to those seen with roach and stone loach exposed to cadmium alone. The significance of these observations in relation to the nature of the intracellular proteins to which cadmium is bound in the three species is discussed in the light of their differential susceptibility to the toxic effects of cadmium. PMID- 2874941 TI - The ionic mechanism associated with the action of putative transmitters on identified neurons of the snail, Helix aspersa. AB - Intracellular recordings were made from identified neurons in the suboesophageal ganglionic mass of the snail, Helix aspersa. The ionic mechanisms associated with acetylcholine excitation and inhibition, dopamine excitation and inhibition, gamma-aminobutyric acid (GABA) excitation and inhibition and serotonin excitation were investigated. Acetylcholine excitation was found to involve an initial increase in sodium conductance while acetylcholine inhibition was a pure chloride event which reversed at membrane potentials more negative than the chloride equilibrium potential. Dopamine excitation appeared to involve only an increase in sodium conductance while serotonin excitation involved an increase in conductance to both sodium and calcium ions. Dopamine inhibition was associated with an increase in potassium conductance but failed to reverse at membrane potentials more negative than the potassium equilibrium potential. GABA excitation involved conductance increases to both sodium and chloride ions while GABA inhibition was a pure chloride event. An attempt was made to estimate the degree of co-operativity of the putative transmitters with their receptors using log-log and Hill plots. The slopes of the line for the log-log plots for acetylcholine excitation and inhibition were 0.88 and 1.1, respectively, suggesting the interaction of one molecule of acetylcholine with the receptor. The slope of the log-log plot for dopamine inhibition was 0.46 while that for serotonin excitation was 0.75. The Hill plots for GABA excitation and inhibition were 1.64 and 1.42, respectively, suggesting that two molecules of GABA are required for receptor activation. PMID- 2874942 TI - Effect of cyanide and verapamil on sodium-free contractures in the frog heart. AB - Sodium-free contractures were studied in myocardial strips from R. pipiens with extracellular sodium (Na0+) replaced by choline chloride and extracellular calcium (Ca20+) varied with EGTA buffer. At calculated Ca02+ below 2.8 X 10(-7) mol/l, no contracture occurred in most of the experiments, even in the presence of cyanide. When Ca02+ was above 2.8 X 10(-7) mol/l, relatively short tension transients of up to 80 sec duration could be avoided if the myocardial strip was previously equilibrated for 20 min in a Na+-Ca2+-free solution. Instead, contractures developed slowly within one to several hours. The maximum contracture was dependent on Ca02+ in a dose-response-like pattern. The time course of contracture development was not affected by verapamil, but KCN significantly increased the rate of resting tension increase. In solutions with normal Na+-Ca2+ content and even in a Na+-Ca2+-free milieu, the cellular ultrastructure was normal. Development of contracture after addition of Ca2+ to the Na+-free solution was combined with ultrastructural damage of the ventricular strip. It is concluded that Na+-free contractures depend on transsarcolemmal net Ca2+ uptake as a sum of Na-Ca-exchange-dependent Ca2+ uptake and active sequestering of intracellular free calcium Ca2+ mediated by sarcolemmal and probably intracellular Ca2+-ATPases. The negative inotropic effect of the Ca blocker verapamil seems not to be mediated by the Na-Ca exchange. PMID- 2874943 TI - Effect of petroleum hydrocarbons on the biliary bile acid composition of rainbow trout (Salmo gairdneri). AB - Biliary bile acid profiles were investigated by thin layer and gas liquid chromatography in fish exposed per os with a Venezuelan crude petroleum or a triglyceride rich oil, olive oil. Neither volume of bile nor bile acid pools were affected, compared to controls, in fish fed either petroleum or olive oil. The response was not uniform, but a small increase in the ratio of the primary bile acids, cholic to chenodeoxycholic, was observed in a number of fish exposed to petroleum. Petroleum appeared not to simply mimic a fatty food source in altering the cholic to chenodeoxycholic acid ratio. The hypothesis that the elevation of mixed function oxygenase enzymes by such potent inducers as petroleum hydrocarbons could markedly alter bile acid profiles, or result in the production of novel bile acid metabolites, was not supported in this study. PMID- 2874944 TI - Presence of corticotropin-like and opiate-like hormones in rat and bovine placental tissues. AB - Acid acetone powder of rat placentas was fractionated on Sephadex G-25 into a void volume peak (R-1) and three retarded peaks (R-2, R-3 and R-4). R-3 contained opiate-like activity and R-4 corticotropin-like activity, suggesting that separate corticotropin-like and opiate-like activities with molecular weight smaller than 5000 were present in rat placentas. Acid acetone powder of bovine placentas contained opiate-like activity which was unretarded on Sephadex G-25. Acid acetone powder of rat brains but not those of lungs, livers or kidneys possessed opiate receptor binding and steroidogenic activities, indicating that the activities in placentas were not due to enzymatically generated artifacts or to peptides contained in blood trapped in the organs. PMID- 2874945 TI - Effect of catecholamines and metal chelating agents on the brain and brown adipose tissue Na,K-ATPase. AB - Catecholamines stimulate Na,K-ATPase activity in the microsomal membranes of the brain and brown adipose tissue. This stimulation is apparent in the absence of soluble, cytosolic inhibitors and exhibits the same characteristics in both tissues: it occurs at high concentrations (10(-6)-10(-4) M) only; there is no difference in potency between isoprenaline, norepinephrine and epinephrine (EC50 = 1-2 X 10(-5) M); the D-stereoisomer of isoprenaline is equally as effective as the L-form; stimulation of Na,K-ATPase may also be achieved by the metal chelators EDTA, EGTA and desferal; the hydrophobic beta-blockers, propranolol and alprenolol, inhibit both the norepinephrine-stimulated and basal levels of enzyme activity at concentrations of 10(-5)-10(-3) M; phenoxybenzamine, an irreversible alpha-adrenergic blocker, inhibits basal Na,K-ATPase as well as norepinephrine stimulated enzyme activity (EC50 = 2.5 X 10(-5) M). Because none of these observations can be related to the properties of the stereospecific adrenergic receptor (alpha or beta), it may be concluded that the catecholamine-Na,K-ATPase interaction is not mediated by the receptor. More probably, catecholamines may antagonize the Na,K-ATPase inhibition caused by some tightly membrane-bound metals (but not vanadium) via the ortho-catechol moiety of the catecholamine molecule. The stimulation of brown fat Na,K-ATPase by catecholamines does not have much relevance to the norepinephrine-stimulated thermogenesis in this tissue. PMID- 2874946 TI - Xenobiotic metabolizing enzymes in spawning English sole (Parophrys vetulus) exposed to organic-solvent extracts of marine sediments from contaminated and reference areas. AB - Female English sole (Parophrys vetulus) within 1-2 days of spawning were exposed by i.m. injection to organic-solvent extracts of marine sediments at the following doses: Eagle Harbor (EHSE, contaminated site)--6.8 mg aromatic hydrocarbons (AHs)/kg body wt; Duwamish Waterway (DSE, contaminated site)--0.52 mg AHs and 0.040 mg chlorinated hydrocarbons (CHs)/kg body wt; Hood Canal (HCSE, reference site)--0.00090 mg AHs/kg body wt. Hepatic aryl hydrocarbon hydroxylase (AHH) activity, measured at spawning, was induced 10-, 23-and 2-fold by EHSE, DSE and HCSE, respectively, compared to sham and vehicle controls. Hepatic glutathione-S-transferase and epoxide hydrolase activities were not affected by any treatment. EHSE, but not DSE or HCSE, inhibited spawning (P less than 0.01) in 36% of the exposed fish and hepatic AHH activity in the non-spawning fish was significantly (P less than 0.05) higher than in the fish that did spawn. These results suggest a potential for reproductive toxicity in benthic fish after exposure to sediment-associated contaminants. PMID- 2874947 TI - Effects of morphine and methionine-enkephalin on the smooth muscle tonus and the contraction induced by transmural stimulation in the carp (Cyprinus carpio) intestinal bulb. AB - The effects of morphine and methionine-enkephalin (met-enkephalin) on the smooth muscle tonus and the contraction induced by transmural stimulation were investigated in the isolated intestinal bulb of carp in vitro. Morphine (30 nM-3 microM) and met-enkephalin (3 nM-5 microM) caused dose-dependent non-sustained contraction. Naloxone (10 nM) inhibited the contraction induced by morphine or met-enkephalin in a competitive manner. Tetrodotoxin (400 nM) or atropine (500 nM) did not inhibit the contraction induced by morphine or met-enkephalin. Cooling of the bath fluid from 20 to 10 degrees C decreased nicotine- and transmural stimulation-induced contraction. But met-enkephalin-induced contraction was not affected. Transmural stimulation-induced contraction (3 Hz) was not affected by pretreatment with morphine, met-enkephalin or naloxone. The results demonstrated that morphine or met-enkephalin caused contraction of the smooth muscle directly through the activation of opiate receptors on the smooth muscle cells and neither morphine nor met-enkephalin regulated the cholinergic neurotransmission presynaptically. PMID- 2874948 TI - Intestinal uptake and retention of copper in the suckling rat, Rattus rattus- III. Effects of closure. AB - The ileum of suckling rats contains a high level of copper, most of which is concentrated within cytoplasmic vesicles of the enterocytes. Intestinal closure, 20-21 days after birth, results in the replacement of enterocytes by cells devoid of these vesicles and there is a concomitant fall in the level of copper in the ileum. Administration of cortisone acetate (0.5 mg/g body wt) to 5-day-old rats results in premature loss of copper-laden ileal enterocytes and an 80-90% decrease in the ileal copper concentration. The loss of copper is mainly from the soluble fraction of the tissue and is proportionally greater from the high molecular weight-protein fraction rather than from the copper complex. PMID- 2874949 TI - Low-molecular weight metalloproteins in tissues of the narwhal (Monodon monoceros). AB - Narwhal (Monodon monoceros) liver and kidney cytosol were fractionated by gel chromatography, anion-exchange chromatography and electrophoresis. Cadmium was associated largely with low molecular weight proteins, while mercury was associated also with high molecular weight proteins, but apparently not because of saturation of the metallothionein mechanism. Eight different electrophoretic bands, four of which were metalloproteins, were found under the "metallothionein" peak. Anion-exchange chromatography yielded five metal peaks while further fractionation on G-50 gave two peaks, one containing almost pure metallothionein (Mt-1) and the other a metalloprotein having twice the molecular weight of metallothionein. Mt-2 was observed, at a much lower concentration than Mt-1, in liver but not kidney. PMID- 2874950 TI - Induction of heavy metal binding groups by dexamethasone and Zn in cultured Chinese hamster ovary cells. AB - Cd binding capacity and pulse polarography were used to study the inducibility of sulfhydryl groups in cultured Chinese hamster ovary cells (wild type and a Cd resistant mutant) in response to dexamethasone (dex) and Zn. Evidence is presented that both the wild type and the mutant responded to dex and Zn treatment by induction of sulfhydryl groups. In wild type for Zn and dex as well as in the mutant for dex, this induction seems to be in the form of sulfhydryls attached to particulate or membrane fractions in the cells. For Zn in the Cd resistant mutant the induction was in the form of metallothionein. PMID- 2874951 TI - Demonstration of specific high-affinity binding sites for [3H]5-hydroxytryptamine in the cestode Hymenolepis diminuta. AB - [3H]5-HT (0.16-8.32 nM) exhibited saturable and specific binding in membrane preparations of Hymenolepis diminuta. The saturation data produced a non-linear Scatchard plot which could be resolved into sites having apparent dissociation constants (Kd) of 0.17 and 8.30 nM for the high-affinity and low-affinity components, respectively. Drug displacement studies, using radioligand concentrations of 0.6 and 6 nM, revealed that the two [3H]5-HT binding components are pharmacologically distinct and do not conform to any known class of 5-HT recognition site. The physiological significance of these putative 5-HT receptors and their potential usefulness for the selection of new antiparasitic agents are discussed. PMID- 2874952 TI - Gastric mucus glycoprotein in different rat strains. AB - The extent of gastric damage induced by aspirin was found to differ according to rat strain. The occurrence of ulcers varied, from high to low, in the following strain order: Donryu, Sprague-Dawley (SD) and Wistar. The content of corpus mucus glycoprotein was essentially the same in all the strains: about 6 mg as hexose of dry tissue. Antral mucus glycoprotein content increased in the order Wistar, SD and Donryu: 7.1, 8.3 and 9.1 mg, respectively. Gastric mucus glycoprotein carbohydrate composition was essentially the same in all three strains. The relatively low proportions of N-acetylglucosamine, galactose and sialic acid from the antrum was a characteristic feature in contrast to mucus glycoprotein from the corpus which contained a high proportion of these sugars. PMID- 2874953 TI - Heavy metal-induced inhibition of active transport in the rat small intestine in vitro. Interaction with other ions. AB - The effect of Hg2+, Cd2+ and Pb2+ on the intestinal transport of D-glucose and L tyrosine was studied in everted sacs of small intestine. Hg2+, Cd2+ and Pb2+ (10( 5) and 10(-4)) singly or in combination inhibit the active transport of D-glucose (10 mM) and L-tyrosine (2 mM) in rat and pigeon small intestine. The presence of other ions (Mg2+, Zn2+ and SeO3(2)) diminishes the toxic effect of heavy metal ions, rendering them less effective. PMID- 2874954 TI - Comparative actions of quisqualate and N-methyl-D-aspartate, excitatory amino acid agonists, on guinea-pig cochlear potentials. AB - We examined dose-dependent changes in the amplitude of guinea-pig cochlear microphonic potentials (CM), summating potentials (SP) and compound auditory nerve action potentials (CAP) produced after perfusing perilymphatic scalae with artificial perilymph containing either the transmitter candidate, L-glutamate; one of the excitatory amino acid agonists, quisqualate, kainate, N-methyl-D aspartate (NMDA) or D-glutamate; or the control, alpha-ketoglutarate. None of these compounds significantly altered CM or SP. Kainate abolished CAP, but only partial suppression occurred using maximal effective doses of quisqualate (67%) or L-glutamate (82%). The remaining compounds had only marginal effects on CAP. The potency of quisqualate (EC50 = 14.8 microM) exceeded that of both kainate (EC50 = 66.9 microM) and L-glutamate (EC50 = 1.41 mM). These data suggest the presence of neuronal, possibly postsynaptic, excitatory amino acid receptor subpopulations which are preferentially sensitive to quisqualate and to kainate, but not to NMDA. These findings are discussed in the framework of our hypothesis that the proposed quisqualate and kainate receptors are normally activated by an endogenous excitatory amino acid such as L-glutamate which the hair cells release as a neurotransmitter. PMID- 2874955 TI - Hepatotoxic effects of CCl4 on English sole (Parophrys vetulus): possible indicators of liver dysfunction. AB - Selected serum parameters (enzyme activities and triglycerides) and liver glutathione and vitamin C concentrations were measured in English sole (Parophrys vetulus) after i.p. injection of carbon tetrachloride (CCl4), a hepatotoxin in fish. Serum lactate dehydrogenase (LDH), alkaline phosphatase (AP) and glutamate dehydrogenase (GDH) activities and the concentration of triglycerides increased in a dose-dependent manner 24 hr post injection. Concentrations of glutathione (reduced and oxidized) and ascorbic acid (vitamin C) in liver did not change in response to CCl4 toxicity 24 hr post injection. These studies indicate that serum AP activity and triglyceride concentrations can be useful in assessing the effects of CCl4-induced liver toxicity in this species of marine fish. Serum LDH and GDH activity should be used with some caution in assessing liver damage in English sole, as other tissues represent more likely sources for serum activity. The levels of liver antioxidants do not appear to be significantly affected, 24 hr post injection, by this particular hepatotoxin. PMID- 2874956 TI - Allergic contact dermatitis from chloromethyl heterocyclic intermediates in the synthesis of a histamine antagonist. AB - Case reports of 3 chemists who worked in a laboratory where heterocyclic chloromethyl compounds, used as intermediates in the synthesis of a histamine antagonist, were being prepared, are here presented. The results of suitable patch tests which were applied are reported and it is concluded from the results that 3 chemical intermediates were responsible for the allergic contact dermatitis in the 3 cases. PMID- 2874957 TI - Biochemical studies of bacterial protein export. PMID- 2874958 TI - Terfenadine in chronic urticaria: a comparison with clemastine and placebo. AB - Terfenadine, a new specific and peripherally acting antihistamine, was compared with clemastine and placebo in a prospective, randomized, double-blind, double dummy, crossover study of the treatment of chronic urticaria. Sixty patients with chronic urticaria participated in this multicenter trial. The treatment time was two weeks per drug treatment, totalling six weeks. Terfenadine proved more effective than clemastine and was associated with significantly less sedation. Few adverse reactions were noted. PMID- 2874959 TI - [Use of lateral risers in mouth protectors used in orthodontics, in sports]. PMID- 2874960 TI - [The relation between peptic ulcer and antral G and D cells]. PMID- 2874961 TI - [Report on the dependence caused by long-term administration of surazepam in 41 cases]. PMID- 2874962 TI - [Ranitidine: a new histamine H2 receptor blockader]. PMID- 2874963 TI - [True renovascular hypertension--a report of 170 cases]. PMID- 2874964 TI - [35 cases of renovascular hypertension treated by percutaneous transluminal angioplasty]. PMID- 2874965 TI - Papers presented at the Committee on Problems of Drug Dependence Symposium on Stimulants and Hallucinogens. June/September, 1984. PMID- 2874966 TI - The stimulants and hallucinogens under consideration: a brief overview of their chemistry and pharmacology. AB - The substances under review are a heterogeneous set of compounds from a pharmacological point of view, though many have a common phenylethylamine structure. Variations in structure lead to marked changes in potency and characteristic action. The introductory material presented here is meant to provide a set of chemical and pharmacological highlights of the 28 substances under consideration. The most commonly used names or INN names, Chemical Abstract (CA) names and numbers, and elemental formulae are provided in the accompanying figures. This provides both some basic information on the substances and a starting point for the more detailed information that follows in the individual papers by contributors to the symposium. PMID- 2874968 TI - Use, indications and distribution in different countries of the stimulant and hallucinogenic amphetamine derivatives under consideration by WHO. AB - Information is presented on legal manufacture, distribution, medical uses and in various countries of the stimulants and hallucinogens under consideration by the World Health Organization (WHO). Data are reported from the Substance Abuse Warning System (SAWS) in the F.R.G. and other surveillance systems regarding illicit manufacture, trafficking and abuse of these compounds internationally. In addition, it is pointed out that assessment of the liability of these compounds for abuse must consider not only the substance itself but also its potential metabolic products. These data, collectively, indicate that the substances currently of most concern with respect to abuse are fenetylline and norpseudoephedrine. PMID- 2874967 TI - Discriminative stimulus properties of phenylisopropylamine derivatives. AB - The phenylisopropylamine unit is a common structural fragment amongst many centrally-acting agents. However, these agents do not necessarily produce similar behavioral effects in test subjects. For example, the phenylisopropylamine derivative amphetamine is a central nervous system (CNS) stimulant whereas its 2,5-dimethoxy-4-methyl analog, i.e. DOM, is considered to be a hallucinogen. Employing animals trained to discriminate either (+)-amphetamine or (+/-)-DOM from saline in a two-lever operant procedure, stimulus generalization studies were conducted to evaluate members of a series of methoxy-substituted, and related, phenylisopropylamines. In this manner, it was possible to classify these agents as to which produced amphetamine-like effects, and which produced DOM-like effects. PMID- 2874969 TI - Epidemiologic issues pertinent to international regulation of 28 stimulant hallucinogen drugs. AB - This paper examines selected epidemiologic issues raised by the consideration of 28 stimulant-hallucinogen drugs for international drug control. New epidemiologic evidence on these drugs is presented, based on laboratory analysis of drug samples obtained from unauthorized channels of distribution in the United States. A proposal is made for experimental evaluation of international drug controls. The proposed approach is to select some of the stimulant-hallucinogen drugs which are not currently responsible for substantial drug-related morbidity and mortality, but which appear suitable for control on the basis of presumed potential for abuse and other characteristics. Then, randomly assign one-half of this group for new drug regulations, leaving the others without new regulation. If proper epidemiologic surveillance were in place, this experimental trial would produce data to help substantiate inferences about drug control efficacy. Difficulties in implementing this proposal are discussed, with emphasis on surveillance measurement problems. Some of these problems are related to the non medical character of much stimulant-hallucinogen drug use. However, other problems such as response inconsistency may affect research in drug epidemiology generally. Data from a recent panel study of psychotherapeutic medicine use are presented to illustrate this possibility. PMID- 2874970 TI - Propylhexdrine. AB - Propylhexedrine, a sympathomimetic with varied medicinal uses, is one of the compounds to be reviewed by the Expert Committee convened by the World Health Organization (WHO) to determine whether the compound should be scheduled under the Convention on Psychotropic Substances. This paper reviews the pharmacology, medicinal uses, toxicity and abuse-potential of propylhexedrine, with special emphasis on toxicity and abuse potential. The primary medicinal use of propylhexedrine is temporary symptomatic relief of nasal decongestion due to colds, allergies and allergic rhinitis. When used as a nasal inhaler for this indication, propylhexedrine reduces nasal airway resistance without producing rebound congestion. Abuse does not occur by nasal inhalation; however, a small amount of abuse of the propylhexedrine containing nasal inhalers occurs by oral ingestion of the contents of the inhaler or by intravenous injection. Propylhexedrine is a central nervous system (CNS) stimulant of low abuse potential, a stimulant of low preference for stimulant abusers compared with amphetamine, methylphenidate, phenmetrazine. PMID- 2874971 TI - Sedative/hypnotic dependence: patient stabilization, tolerance testing, and withdrawal. AB - Physical dependence to sedative/hypnotic drugs is not an uncommon clinical problem. The withdrawal syndrome is analogous to alcohol withdrawal, except the duration of the syndrome occurs over a longer period of time with the symptoms being less intense than generally encountered with alcohol. The potential for withdrawal reactions is probably greater for the shorter-acting agents than the longer-acting drugs. Potentially dependent sedative/hypnotic users require stabilization of their symptoms initially, followed by tolerance testing. If tolerant, the patients should be withdrawn using either a long-acting sedative/hypnotic (e.g., diazepam) or phenobarbital. Compared to other benzodiazepines and barbiturates, diazepam appears to be the drug of choice for treating dependent patients. Diazepam is rapidly absorbed and distributed to the brain and therefore useful for stabilization and tolerance testing. It is metabolized on chronic administration to a long-acting metabolite, desmethyldiazepam, which makes the drug ideal for a tapered withdrawal schedule. PMID- 2874973 TI - [Positive correlation between glucose and glutamate in the cerebrospinal fluid in man]. PMID- 2874972 TI - [Thyrotropin-displacing antibodies in thyroid gland diseases]. AB - Thyroid-stimulating antibodies were assayed in 798 patients with thyroid diseases and 122 controls by means of a heterologous radioreceptor assay as thyrotropin displacement activity (TDA). With an intraassay variance of 5-6% and an interassay variance of 8-13% in higher TDA values, test results were well reproducible. Thus, TDA assay is suitable for routine testing and follow-up of titers in the upper range. With only few exceptions TDA values of F greater than or equal to 11% are found exclusively in Graves' disease (sensitivity 39.2%; specificity vs other thyroid diseases 99.7%). In patients with functional autonomy in nodular goitre (Plummer's disease) TDA is consistently negative. TDA measurement is a valuable means for the detection of Graves' disease and for differential diagnosis of hyperthyroidism of undetermined pathogenesis. PMID- 2874974 TI - Zopiclone. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy as an hypnotic. AB - Zopiclone is the first of the cyclopyrrolones, a new class of psychotherapeutic agents possessing a pharmacological profile of high efficacy and low toxicity similar to that of the benzodiazepines. Binding is thought to occur to the benzodiazepine receptor complex, or to a site closely linked to this complex. Although zopiclone exhibits anticonvulsant, muscle relaxant and anxiolytic properties in animals, it finds better use as an hypnotic because of marked sedating effects. In clinical trials, zopiclone (usually 7.5 mg) improved sleep in chronic insomniacs similarly to nitrazepam 5 mg, flurazepam 15 to 30 mg, triazolam 0.5 mg and temazepam 20 mg, but in a single study was slightly less effective than flunitrazepam 2 mg in some evaluation criteria. Sleep induction before surgical procedures in hospitalised patients is satisfactory with zopiclone, but when the drugs are administered a few hours before surgery, diazepam appears to be more effective in alleviating preoperative anxiety. Minimal impairment of psychomotor skills and mental acuity occurs in the morning after a bedtime dose of zopiclone, which has a short half-life of about 5 hours and no long acting metabolites. No serious side effects have been reported in the relatively small number of patients studied to date; the development of 'bitter taste' does not deter patients from continuing therapy. Thus, with its short duration of action zopiclone is a useful alternative to other hypnotics, especially in patients intolerant of residual effects the morning after taking an hypnotic. PMID- 2874977 TI - Current management of Zollinger-Ellison syndrome. AB - Patients with Zollinger-Ellison syndrome require that management decisions be made to control the gastric acid hypersecretion and treatment directed at the gastrinoma itself. The advent of newer antisecretory drugs and increased knowledge of the natural history of this disease have led to major changes in the management of each of these two areas. Recent studies have demonstrated that treatment with the currently available histamine H2-receptor antagonists (cimetidine, ranitidine) with or without an anticholinergic agent will control gastric acid secretion in almost all patients. These studies have also shown that most patients require higher doses than those used routinely to treat peptic ulcer, treatment is only successful if an adequate dose of antisecretory drug is used and must be monitored by measuring gastric acid hypersecretion, and established criteria to regulate the dose must be used. Newer more potent antisecretory drugs such as famotidine or omeprazole will facilitate management of gastric hypersecretion but are not yet currently available. Highly selective vagotomy should be considered in those patients who require high doses of cimetidine or ranitidine. Total gastrectomy should be reserved for those patients unwilling or unable to take oral medication. Although aggressive surgery is not warranted in most patients because overall prognosis is excellent, tumour status should be assessed in all patients by imaging studies (CT scan, ultrasound, selective angiogram). Patients without metastatic disease and without the MEN-1 syndrome (multiple-endocrine-neoplasia type 1) should undergo exploratory laparotomy by a surgeon experienced in treating this disease, with studies suggesting a cure rate of approximately 20%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2874976 TI - Buspirone. A preliminary review of its pharmacological properties and therapeutic efficacy as an anxiolytic. AB - Buspirone hydrochloride (HCl)1 is a new anxiolytic with a unique chemical structure. Its mechanism of action remains to be elucidated. Unlike the benzodiazepines, buspirone lacks hypnotic, anticonvulsant and muscle relaxant properties, and hence has been termed 'anxioselective'. As evidenced by a few double-blind clinical trials, buspirone 15 to 30 mg/day improves symptoms of anxiety assessed by standard rating scales similarly to diazepam, clorazepate, alprazolam and lorazepam. Like diazepam, buspirone is effective in patients with mixed anxiety/depression, although the number of patients studied to date is small. In several studies, a 'lagtime' of 1 to 2 weeks to the onset of anxiolytic effect has been noted; hence motivation of patient compliance may be necessary. Sedation occurs much less often after buspirone than after the benzodiazepines; other side effects are minor and infrequent. In healthy volunteers, buspirone does not impair psychomotor or cognitive function, and appears to have no additive effect with alcohol. Early evidence suggests that buspirone has limited potential for abuse and dependence. Thus, although only wider clinical use for longer periods of time will more clearly define some elements of its pharmacological profile, with its low incidence of sedation buspirone is a useful addition to the treatments available for generalised anxiety. It may well become the preferred therapy in patients in whom daytime alertness is particularly important. PMID- 2874978 TI - Neurotransmitter changes during development of cortical neuronal cultures. AB - Benzodiazepine (BDZ) ligands clonazepam (CLO) and Ro5-4864 which preferentially bind to neuronal and non-neuronal elements, respectively, have been used to follow neuronal and non-neuronal development in fetal murine cortical cultures. CLO-displaceable BDZ binding, choline acetyltransferase (CAT) activity, high affinity delta-aminobutyric acid (GABA) uptake, and glutamic acid decarboxylase (GAD) activity reached a maximum value at the end of the second week in culture reflecting maximum neuronal maturation and development. There is a developmental order of these four functions: CAT activity (main enzyme in the synthesis of acetylcholine, a stimulating neurotransmitter) reached maximal levels first, 3H GABA uptake and CLO-displaceable flunitrazepam receptor binding reached maximal levels 1 day later, and 4 days later GAD activity (primary enzyme in the synthesis of GABA, an inhibitor neurotransmitter) reached maximal levels. PMID- 2874979 TI - [The microstructure of the diffusion layer between solder and fired precious metal alloys after furnace brazing]. PMID- 2874980 TI - [Structure and strength of silver solders used in orthodontics after treatment with commercial cleansers]. PMID- 2874975 TI - The haemodynamic effects of nifedipine, verapamil and diltiazem in patients with coronary artery disease. A review. AB - Of the 3 most widely used calcium antagonists--nifedipine, verapamil and diltiazem--nifedipine is the most potent arterial vasodilator. Increases in cardiac output and coronary blood flow following nifedipine administration result in part from the afterload reduction. Reflex adrenergic stimulation produces an increase in heart rate and masks a direct inhibitory effect on myocardial contractility. The negative inotropic action of nifedipine is observed during intracoronary administration or may be made apparent by concurrent beta-blocker therapy. While verapamil is also a potent vasodilator, negative inotropic and dromotropic properties are more apparent in therapeutically used dosages. Reflex sympathetic activation is also triggered by verapamil, with an offsetting of the negative inotropic effects such that little change in cardiac output results. A decrease in myocardial oxygen consumption, with or without a decrease in coronary sinus blood flow, has regularly been observed following verapamil administration. Reduced oxygen demand appears to be a major mechanism of its antianginal effect. The heart rate X systolic pressure product is decreased both by the fall in arterial pressure and, particularly after oral administration, by a decrease in heart rate. Diltiazem produces similar haemodynamic and electrophysiological effects to those of verapamil but has less potency in inducing arterial dilatation and more of a tendency to slow the heart rate. Diltiazem does not appear to cause significant increases in coronary blood flow or bring about improvement in ejectional and isovolumic indices of myocardial contraction - evidence of its intrinsic negative inotropic effect. PMID- 2874981 TI - [Benzodiazepines and benzodiazepine receptors]. PMID- 2874982 TI - [Interaction of neurostimulators and non-inhalation anesthetics]. PMID- 2874983 TI - [The 4 second sleep spindle periodicity]. AB - Polysomnographic EEGs were recorded from 12 adult volunteers between the ages of 20 and 50 years. They were given placebo, pentobarbital, carbromal, methaqualone, flunitrazepam, lormetazepam and triazolam. The visual evaluation was aimed at finding periodic sequences of centro-parietal sleep spindles at 13-15/s. Four consecutive spindles following each other regularly were defined as the shortest sequence. Placebo showed the following results: a considerable interindividual variance with 2 to 6 such sequences on the one hand and 25 on the other hand for each night. sequences with six periodically consecutive spindles dominated; the longest sequence contained 15 spindles. the inter-spindle distance was 4 seconds (m: 4.09; mean 4.14 s). All hypnotics caused an increase in periodic spindle sequences. Volunteers with a low tendency to have periodic spindle sequences remained at the lower end of the scale when taking hypnotics. Hypnotics increased the amount of longer spindle sequences, however, the average was still at sequences of 4-11 consecutive spindles. The inter-spindle distance became longer with all hypnotics; 4.34 s (carbromal) up to 4.58 s (flunitrazepam). Volunteers with a low tendency to have periodic spindle sequences showed shorter distances between spindles vice versa. Benzodiazepines do not reveal any characteristics due to their pharmacokinetic structure. PMID- 2874984 TI - Growth hormone-releasing hormone. AB - The identification of GRH has been followed by an extraordinarily rapid rate of knowledge accumulation. Within a period of slightly more than 3 yr since the structure of the GRH was determined, nearly 500 papers have been published pertaining to the hormone. Extensive knowledge of its anatomy, chemistry, molecular biology, physiology, and pathology has been gathered and, in particular, studies in humans have proceeded faster than with any other of the hypophysiotropic hormones. New insights have been gained with respect to the pathogenesis of both GH deficiency and GH excess states, and the use of GRH and its analogs as diagnostic and therapeutic agents already represents a reality. PMID- 2874985 TI - The hormonal control of testicular descent. PMID- 2874986 TI - Comparative study in mice of ten 1,4-benzodiazepines and of clobazam: anticonvulsant, anxiolytic, sedative, and myorelaxant effects. AB - We will present data from the comparison between four tests in mice of 10 1,4 benzodiazepines and one 1,5-benzodiazepine (clobazam). The tests used were: the "4 plates test" of anxiolytic activity; the electroshock test to determine the anticonvulsive effects; actimetry to predict the sedative effect on motricity; and traction test to predict the myorelaxant effect. The latter two tests have been suggested to be predictive of side-effects that damage psychomotor efficiency in human patients. A comparison of ED50s determined from the predictive tests of the therapeutic effect and those of the side-effects led to the calculation of ratios considered to be predictive of the safety margin. A classification according to this margin shows the advantages of the 1,5 benzodiazepine compared with the 1,4-benzodiazepines. Despite the caution needed in the extrapolation of the results from animals to humans, this work stresses the interesting place that the 1,5-benzodiazepine seem to hold as anticonvulsant in clinical practice. PMID- 2874987 TI - Comparison of three media for culture of Bordetella pertussis. PMID- 2874988 TI - Synthesis of ATP by soluble mitochondrial F1 ATPase and F1-inhibitor-protein complex in the presence of organic solvents. AB - The F1 and F1-inhibitor-protein complex synthesized tightly bound ATP from ADP and Pi when the organic solvents dimethylsulfoxide (20-50% v/v), ethylene glycol (20-60% v/v) or poly(ethylene glycol) 4000 and 8000 (30-50% w/v) were included in the assay media. There was no synthesis of tightly bound ATP in the absence of organic solvents. In the presence of 50% dimethylsulfoxide, maximal synthesis of ATP was obtained at pH values between 6.5 and 7.7. In both F1 and F1-inhibitor protein there was no synthesis of ATP in the absence of MgCl2. The rate of ATP synthesis became faster as the MgCl2 concentration in the medium was raised from 0.1-10 mM. The Km for Pi of F1 was in the range of 0.8-1.5 mM. The Km for Pi of the F1-inhibitor-protein was much higher than that of F1 and could not be measured. In the presence of 10 mM MgCl2 and 2 mM Pi, the rate constants of ATP synthesis by F1 and F1-inhibitor-protein were 5.2-10.4 h-1 and 3.5-5.9 h-1 respectively. For both enzymes the rate constant of ATP hydrolysis was 0.69 h-1. The tightly bound ATP of F1 and F1-inhibitor-protein were hydrolyzed at a much slower rate when either the Pi concentration or the MgCl2 concentration was suddenly decreased. Both in presence and absence of Mg2+, 40-60% of the radioactive tightly bound ATP synthesized by F1 was hydrolyzed when non radioactive ATP was added to the assay medium. This was not observed when F1 inhibitor-protein was used. PMID- 2874989 TI - Suanzaorentang in cardiac patients with anxiety. AB - In 60 patients with cardiac symptoms and anxiety, the anxiolytic effect of the ancient Chinese remedy Suanzaorentang has been studied. It was a promising anxiolytic remedy, without apparent adverse effects on the cardiovascular system, and appearing not to interact with other drugs. PMID- 2874990 TI - Effects of carbamazepine and valproic acid on brain immunoreactive somatostatin and gamma-aminobutyric acid in amygdaloid-kindled rats. AB - Somatostatin and gamma-aminobutyric acid (GABA) concentrations were evaluated in the brain of kindled rats treated chronically with carbamazepine and valproic acid. Kindled seizures were almost completely blocked by treatment with carbamazepine, whereas the effect of valproic acid was partial, suppressing only generalized seizures. The duration of after-discharge in amygdala was suppressed by carbamazepine not by valproic acid. Carbamazepine induced a decrease in immunoreactive somatostatin concentration and an increase in GABA concentration in the temporal cortex of kindled rats. Valproic acid induced only an increase in GABA concentration. The results suggest that somatostatin may be associated with the suppression of focal seizure in amygdala and GABA may have a role in the suppression of generalized seizures. PMID- 2874991 TI - Comparison of alpha-adrenoceptor involvement in the antinociceptive action of tizanidine and clonidine in the mouse. AB - The effect of drugs that influence the opioidergic and monoaminergic neuronal systems on the antinociceptive action of tizanidine [5-chloro-4-(2-imidazolin-2 yl-amino)-2,1, 3-benzothiodiazole] was compared with their effect on the action of clonidine. The potency of the clonidine-induced antinociceptive action was 1.83 and 7.75 times greater than that of tizanidine in the tail-flick and acetic acid-induced writhing tests, respectively. The action of tizanidine and clonidine was completely antagonized by pretreatment with yohimbine, an alpha 2 adrenoceptor blocker, but not by prazosin, an alpha 1-adrenoceptor blocker. Other alpha-adrenoceptor blockers, phenoxybenzamine and phentolamine, also attenuated the action of tizanidine and clonidine but the potency of these drugs was less than that of yohimbine. An opioid antagonist (naloxone), drugs influencing the serotonergic neuronal system (p-chlorophenylalanine, 5,6-dihydroxytryptamine, cyproheptadine), and drugs influencing the catecholaminergic system (alpha-methyl p-tyrosine, diethyl-dithiocarbamate, 6-hydroxydopamine, haloperidol) showed no effect on the action of tizanidine and clonidine. From these results, it appears that alpha 2-adrenoceptors might be of importance in mediating the tizanidine and clonidine antinociceptive action in the tail-flick test. PMID- 2874992 TI - Expression of proliferating cell nuclear antigen (PCNA)/cyclin during the cell cycle. AB - The expression of proliferating cell nuclear antigen (PCNA), also called cyclin, was quantified in the cell lines SP2/0 and MOLT-4 and in mouse splenocytes induced to proliferate in vitro with mitogens. Autoantibody from a patient with systemic lupus erythematosus was used to label PCNA in cell suspensions after the cells had been fixed and permeabilized. In the same cells DNA was stained by propidium iodide. The cells were then analysed by flow cytometry for PCNA and DNA content. The PCNA profiles in proliferating spleen cells and the cell lines were similar. Most G0-G1 cells did not express significant amount of PCNA. A dramatic increase in PCNA immunofluorescence was observed in late G1 cells, and further increases were observed in S-phase cells. G2-M cells showed a reduced level of PCNA immunofluorescence relative to S-phase cells but were still elevated relative to G0-G1 cells. Proliferating cells arrested at the G1-S boundary by exposure to cytosine arabinoside showed an increased PCNA immunofluorescence as compared to unstimulated cells. PMID- 2874993 TI - Asthma therapy: basic mechanisms. PMID- 2874994 TI - New isoxazole derivatives with a potent and selective beta 2-adrenergic activity. AB - A series of 1-(3-subst-5-isoxazolyl)-2-alkylaminoethanol derivatives was synthesized and tested in order to evaluate the effectiveness of the isoxazole ring in replacing the catechol moiety of beta-adrenergic compounds. Direct binding studies and the influence on beta-receptors mediated responses in isolated guinea-pig atria and guinea-pig trachea were investigated to determine the pharmacological profile of the new derivatives. The results indicate that some derivatives with proper substitution in the isoxazole ring and in the aminoalcohol chain displayed a marked selectivity towards beta 2 tracheal receptors. In vivo studies confirmed this profile, and the derivative 1-(3-bromo 5-isoxazolyl)-2-tert.butyl aminoethanol hydrochloride was selected and further developed as a potential bronchodilatory agent. PMID- 2874995 TI - [Thiazolylalkylamines: synthesis of analogs of imidazolylethylamines and their effect on gastric secretion]. AB - As a part of a study on H2-agonists, the preparations and properties are reported for a representative group of 2-aminothiazolethylamine derivatives which contain the gastric secretion stimulating S-aminoalkylisothiourea moiety. The test compounds were obtained by known methods or from 2-(2-amino-5-thiazolyl)ethyl chloride and were tested for their possible histamine-like activities on different biological substrates. From the biological results it appears that the behaviour of the substances is rather complex, but the following general observations can be pointed out: the contracturant properties, sometimes quite marked, do not derive from direct H1-specific activities; the effects, particularly evident in stimulating in vitro or in vivo gastric secretion, in relaxing gall-bladder smooth muscle, on auriculae and/or on blood pressure, are not competitively antagonized by cimetidine; none of the tested compounds proved to be an antagonist of histamine H2-receptors, while one of them is found to inhibit competitively the H1-receptors. On the basis of structure-activity relationships it can be excluded that the iuxta-nuclear NH2 group of 2 aminothiazolethylamines reacts, in some way, with the H2-receptors, since, in this case, the 2-aminothiazole group is not a pharmacophore like the 2 aminoimidazole or isothiurea group. Consequently the hypotheses, that the flexibility of the molecule is a fundamental requirement for the H2-stimulating properties of S-(3-dimethylaminopropyl)isothiurea and that the different activities of 2-aminohistamine, in comparison with those of 2-methylhistamine, are due to the existence of a hydrophilic area suitable for the allocation of the iuxta-nuclear NH2 group in the H2-receptor, are strengthened. PMID- 2874996 TI - Aminoethers of (+)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]-octan-6-hydroxyimine with hypotensive activity. II. AB - The synthesis of a series of N-substituted 3-amino-2-hydroxypropyl ethers (III a 1) starting from (+)-1,3,3-trimethyl-2-oxabicyclo [2.2.2]-octan-6-hydroxyimine is described. Some of these compounds showed a remarkable hypotensive and a weak bradycardic activity in rats, as well as a moderate local anesthetic activity in mice. All compounds were found to be devoid of antiarrhythmic activity in rats and of beta-blocking activity in dogs. PMID- 2874997 TI - [Work organization for health officer assistants in rural district epidemiological health stations of the Moldavian SSR]. PMID- 2874998 TI - [History of feldsher training in prerevolutionary Belorussia]. PMID- 2874999 TI - [Effect of neuroleptics on the effects of self-stimulation of the ventral tegmentum]. PMID- 2875000 TI - [A method of problem-free oven soldering using a Japanese "spider"]. PMID- 2875001 TI - Hormones, neurosecretions, and growth factors as signal molecules for intercellular communication. AB - Chemical signals, whether in the form of hormones, neurosecretions (neurotransmitters and neuropeptides), or growth factors and chalones are used to communicate information to cells at all stages of their life cycle. These signals inform the cells when it is time to progress through developmental change, when to change the rates of various activities (e.g. metabolism or contraction), and, in some cases, even when it is time to die. Throughout all of these interactive exchanges, the signal molecule itself carries no intrinsic message of a universal nature. The chemical identity of the signal molecule has meaning only for those cells competent to receive the signal (i.e. does it possess an appropriate receptor?). Moreover, it is the nature of the cell receiving the signal (itself the product of innumerable previous encounters with signals from other cells) that dictates the specific response that a particular signal will evoke. The signal emitted by the communicating cell only informs the target cell that it is time to act in a manner consistent with that signal. The majority of the discussion has been from the perspective of vertebrate organisms. Moreover, of necessity, the discussion has been general and superficial. The primary objective of the preceding discussion has been to underscore major similarities and differences existing among hormones, neurosecretions (neurotransmitters and neuropeptides), and growth factors as information-bearing substances used in communication among vertebrate cells. It should be realized that similar means of communication are employed by multicellular invertebrates, by plants, and even by single-celled organisms such as the protists and bacteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875002 TI - Phosphatidylserine and phorbol myristate acetate stimulation of human lymphocyte guanylate cyclase. AB - Guanylate cyclase activities of human lymphocyte membrane and cytosol preparations are stimulated up to three-fold by the direct addition of phosphatidylserine. Phorbol 12-myristate 13-acetate (PMA) greatly augments the effect of phosphatidylserine, but has only a small effect when added alone. Stimulation involves an increase in Vmax, with no change in Km. Inhibitor studies suggest that stimulation may be mediated by protein kinase C, but not by phospholipase or lipoxygenase. PMID- 2875003 TI - Methylprednisolone as an intervention following myocardial infarction. The Solu Medrol Sterile Powder AMI Studies Group. AB - Results of early studies support the concept that steroid treatment may reduce mortality from acute myocardial infarction. This double-blind, randomized, 1118 patient study was performed to determine if methylprednisolone sodium succinate (MPSS, Solu-Medrol Sterile Powder, The Upjohn Company) reduced 28-day mortality following myocardial infarction complicated by cardiac failure. Treatment with 30 mg/kg intravenous MPSS (maximum dose, 3 g) resulted in 28-day mortality rates of 11.7% with MPSS and 9.9% with placebo when treatment was initiated within six hours of the onset of chest pain (Group 1). Mortality rates at 28 days were 10.4% with MPSS and 14.7% with placebo when the treatment was initiated 6-12 hours after onset of chest pain (Group 2). In the late-treatment group, six-month mortality rates were 13.7% with MPSS and 20.3% with placebo (p = 0.08). Analysis of data by life table methods showed similar survival rates between MPSS- and placebo-treated patients in Group 1. In Group 2, survival rates were increased in MPSS-treated patients in the intervals from 48 hours through seven days (p = 0.04) and from three months through six months (p = 0.03). A Cox regression analysis showed that the relative risk of death for Group 1 patients was similar, regardless of treatment; Group 2 patients on MPSS had a significantly decreased relative risk of death (p less than 0.01). MPSS treatment was not associated with increased incidence of myocardial rupture, cardiac aneurysm, early malignant ventricular arrhythmias, or other adverse cardiac events. PMID- 2875004 TI - Hormonal signals and intracellular messengers for renin secretion. PMID- 2875005 TI - Glutamine synthetase mRNA in cultured 3T3-L1 adipocytes. Complexity, content and hormonal regulation. AB - Glutamine synthetase (GS) activity increases more than 100-fold during adipocyte differentiation of cultured 3T3-L1 cells. We now find that Northern hybridization analysis of RNA from 3T3-L1 adipocytes with a rat GS cDNA clone (pGSRK-1) yields two hybridizable GS RNAs of length 3.2 and 1.6 kilobases (kb). Densitometric analyses of autoradiographs of the Northern blots probed with pGSRK-1 indicate that the 3.2 kb GS-specific RNA is at least 4- to 5-fold more abundant than the 1.6 kb GS RNA. Analyses of both total and poly(A+)RNA from 3T3-L1 adipocytes yielded similar results. (It is noteworthy that an mRNA of 1.2 kb would be sufficient to encode the 42 500 Da GS subunit.) Quantitative dot-blot hybridization analysis indicates that dexamethasone increases GS mRNA while both insulin and dibutyryl cAMP decrease GS mRNA and/or prevent the dexamethasone mediated increase. Our data suggest that there are at least two GS mRNAs in 3T3 L1 adipocytes and that they are regulated in parallel by dexamethasone, insulin and dibutyryl cAMP. PMID- 2875006 TI - Maintenance of murine oocyte meiotic arrest: uptake and metabolism of hypoxanthine and adenosine by cumulus cell-enclosed and denuded oocytes. AB - To analyze the potential mechanisms by which hypoxanthine and adenosine maintain meiotic arrest in mouse oocytes this study focused on: the uptake and metabolism of hypoxanthine and adenosine; the effect of inhibitors of inosine monophosphate (IMP) dehydrogenase on purine-mediated meiotic arrest; and the role of adenosine metabolism on the maintenance of meiotic arrest. Although the denuded oocyte can take up radiolabeled hypoxanthine and adenosine, an intact cumulus oophorus greatly augments uptake of these molecules (and/or metabolites). Both of these compounds were completely metabolized during incubation in vitro: hypoxanthine was apparently metabolized to uric acid and adenosine was metabolized to ADP; a small amount of each compound was also converted to inosine by cumulus cells and transferred to the oocyte. The IMP dehydrogenase inhibitors, bredinin and mycophenolic acid (MA), induced, in a dose-dependent manner, the resumption of maturation in cumulus cell-enclosed oocytes maintained in meiotic arrest by hypoxanthine but had no effect on denuded oocytes. MA did not induce maturation when meiotic arrest was maintained by guanosine. Nor did MA alter the uptake of hypoxanthine by cumulus cell-enclosed oocytes. The poorly metabolized analog of adenosine, 2-chloroadenosine, was as effective as adenosine in its synergistic action with hypoxanthine in maintaining meiotic arrest. It is concluded that hypoxanthine and adenosine are metabolized within the oocyte-cumulus cell complex; xanthyl and/or guanyl compounds are produced by oocyte-cumulus cell complexes in the presence of hypoxanthine and play an important role in the maintenance of meiotic arrest; and adenosine need not be metabolized to act synergistically with hypoxanthine in maintaining meiotic arrest. PMID- 2875007 TI - Neural tube-derived factors influence differentiation of neural crest cells in vitro: effects on activity of neurotransmitter biosynthetic enzymes. AB - Previously, we have demonstrated that a factor present in chick embryo extract or medium conditioned by neural tube cells supports adrenergic differentiation of some neural crest cells in vitro. These studies have been extended here to examine the effects of this factor(s) on the development of enzymes involved in neurotransmitter biosynthesis. The time course of expression of choline acetyltransferase (ChAT), a marker for cholinergic cells, and dopamine-beta hydroxylase (DBH), a marker for adrenergic cells, was examined in neural crest cell cultures grown under three conditions: in medium containing 10% embryo extract, in medium containing 2% embryo extract, and in medium containing 2% embryo extract that was conditioned by neural tube cells (NTCM). Significant levels of DBH activity were measured in neural crest cell cultures grown in 10% embryo extract containing medium or in NTCM, while only low levels were present in cultures grown in medium containing 2% embryo extract. In contrast, ChAT activity was inhibited by NTCM in comparison to levels in both 10 and 2% embryo extract containing medium. As a preliminary characterization of the factor(s) present in chick embryo extract, we have fractionated embryo extract and find that a pool of 10 kDa or less can support adrenergic differentiation of some neural crest cells. These results suggest that low molecular weight factors present in embryo extract and NTCM support adrenergic expression of neural crest cells, whereas NTCM suppresses cholinergic expression. PMID- 2875008 TI - Modulation of glucose transport in hamster adipocytes by insulin and by beta- and alpha 2-adrenoceptor agonists. AB - Glucose transport in hamster adipocytes and its modulation by insulin and isoprenaline was characterized with the aid of the non-metabolizable hexose 3-0 methylglucose. Insulin stimulated the initial uptake rates by an increase in Vmax of the transport without any detectable change in Km. The hormone concentration producing half maximal stimulation was identical to that required in rat adipocytes. However, hamster adipocytes were much less responsive to insulin (3 fold stimulation as compared to a 12-fold stimulation in rat fat cells), and maximal transport rates were 10-fold lower than that observed in rat adipocytes. Accordingly, the number of glucose transporters, as assessed by glucose inhibitable cytochalasin-B binding, was considerably lower in plasma membranes of hamster adipocytes. Moreover, no transporters were detected in the low-density microsomes which in insulin-sensitive cell types represent the intracellular pool of recruitable glucose transporters. The relative insulin resistance of the hamster fat cells may therefore be due to a depleted pool of intracellular glucose transporters. In the presence of adenosine, the beta-adrenoceptor agonist isoprenaline produced a moderate stimulation of the basal transport rate which was antagonized by the alpha 2-agonist clonidine. If adenosine deaminase was added in order to remove endogenous adenosine, isoprenaline inhibited the insulin stimulated transport by 50%. In contrast to the stimulatory effects of insulin and isoproterenol, the inhibitory effect of the catecholamine was reversed by cooling the cells to 22 degrees. Glucagon produced a comparable inhibition, suggesting that the inhibitory effect was mediated by adenylate cyclase or its regulatory subunits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875009 TI - Pneumatosis intestinalis in a patient with polyarteritis nodosa. AB - Necrotizing enterocolitis of the small bowel in polyarteritis nodosa is rare. In the proper clinical setting, pneumatosis intestinalis and mesenteric air are characteristic of this entity. PMID- 2875010 TI - Effects of corticotropin-releasing factor on plasma motilin and somatostatin levels and gastrointestinal motility in dogs. AB - The effects of intracerebroventricular and intravenous administration of corticotropin-releasing factor (CRF) on gastrointestinal motility, motilin induced gastric motor response, and plasma motilin and somatostatin levels were investigated in fasted dogs chronically prepared with strain gauge transducers on the antrum and proximal jejunum. Administered intracerebroventricularly at doses of 20 and 100 ng/kg in fasted dogs, CRF suppressed for 4-5 h the gastric cyclic migrating motor complex. A similar dose (100 ng/kg) administered intravenously was inactive. Corticotropin-releasing factor administration by the intravenous route at 100 ng/kg did not alter the cyclic plasma motilin and somatostatin variations associated with the cyclic gastric motor events. During the blockade of antral migrating motor complex induced by intracerebroventricular administration of CRF, cyclic peaks of plasma motilin were absent whereas those of somatostatin persisted. The gastrointestinal migrating motor complex induced by the intravenous administration of porcine motilin (0.25 microgram/kg) was abolished when motilin was injected 2 h after the intravenous administration of CRF (100 ng/kg), whereas a similar dose of CRF administered intracerebroventricularly did not abolish the antral and jejunal motor responses to motilin. It is concluded that in fasted dogs, CRF administered centrally affects the interdigestive gastric motility and the release of motilin but not that of somatostatin. These results also suggest that the intracerebroventricular CRF-induced blockade of motilin release is responsible for the inhibition of gastric migrating motor complex and circulating CRF is able to affect the gastric motor response to porcine motilin through a peripheral mechanism that does not involve somatostatin and motilin secretion. PMID- 2875011 TI - Successful treatment of obsessive-compulsive disorders. AB - Behavioral therapy and drugs have significantly improved obsessive-compulsive disorder (OCD) symptoms. A variety of behavioral therapy methods have been employed, but exposure and prevention of response, particularly, have reduced ritualistic actions of many OCD patients. Many psychoactive drugs have been tried; the tricyclic antidepressant drugs (clomipramine or Anafranel), especially in research outside the United States, have alleviated OCD symptoms as well as depression. Compulsive rituals have responded more often than obsessive actions to both behavioral and psychopharmacological therapy. Recent research has suggested that psychophysiological as well as traditional psychogenic factors may contribute to the etiology, course, and alleviation of OCD. PMID- 2875012 TI - A study of physician preferences in the management of depression in the general medical setting. AB - Although more than 30% of ambulatory medical patients are depressed, little is known about how their depression is managed in the primary care setting. We surveyed 282 primary care physicians at two internal medicine and four family medicine programs. We asked these physicians to describe how they actually managed depression in their depressed medical patients and how they would manage ten hypothetical depressed medical patients. Demographic and attitudinal data were also obtained. Physicians reported that they utilized a wide variety of treatments for their depressed patients. They indicated that they would recommend counseling twice as many depressed patients as they would recommend medicating or referring. Over 30% of the variance in self-reported preferences to recommend particular treatments for depression was accounted for by physician characteristics. Prior experience with a treatment strategy was a significant factor in predicting a recommendation for future use of a treatment independent of other considerations such as endorsement of positive attitudes about the efficacy or benefits of a treatment. Prior experience was also more important than physician sociodemographics as a predictive variable. The clinical and educational implications of these findings for psychiatrists and primary care physicians are discussed. PMID- 2875013 TI - Nucleotide sequence and expression of the pneumococcal autolysin gene from its own promoter in Escherichia coli. AB - Autolysins are enzymes that have several important biological functions and also seem to be responsible for the irreversible effects induced by the beta-lactam antibiotics. The pneumococcal autolysin gene (lyt) has been subcloned from the plasmid pGL30 [Garcia et al., Mol. Gen. Genet. 201 (1985) 225-230] and we have found that the E form of the autolysin is synthesized in Escherichia coli using its own promoter. The high amount of autolysin obtained in the heterologous system when the lyt gene is present in different orientations in the recombinant plasmids studied supports the idea that the autolysin promoter could be a strong one. The nucleotide sequence of the HindIII fragment of pGL80 (1213 bp) containing the autolysin structural gene has been determined. A unique open reading frame (ORF) has been found, a consensus ribosome-binding site and -10 and -35 promoter-like sequences as well as A + T-rich regions farther upstream were also identified. The lyt ORF encodes a protein of 318 amino acid residues having a calculated Mr of 36,532, which agrees with previous size estimates based on electrophoretic migration [Holtje and Tomasz, J. Biol. Chem. 251 (1976) 4199 4207; Briese and Hakenbeck, Eur. J. Biochem. 146 (1985) 417-427]. Our results also demonstrate that the lyt-4 marker represents the first example of a mutation in a structural gene of a bacterial autolysin. The polarity profile of the pneumococcal autolysin supports previous suggestions about the localization of this enzyme in the normal cell. PMID- 2875014 TI - [Priority objectives of hygienists in the realization of the decisions of the 27th Congress of the CPSU]. PMID- 2875015 TI - [Problems of occupational hygiene discussed at the 7th All-Russian Congress of Hygienists and Sanitary Physicians]. PMID- 2875017 TI - Inhibition by somatostatin of LH-RH-induced LH release in normal menstruating women. AB - The present study was carried out in order to establish whether the concomitant treatment with somatostatin (SRIH) is capable of modifying gonadotrophin release in response to LH-RH administration in normal women during follicular, periovulatory, and luteal phases. SRIH was administered in a dose of 5.55 micrograms/min over 180 min and LH-RH (100 micrograms) was injected as a bolus at 90 min after the beginning of SRIH infusion. Within the dose used, SRIH significantly reduced LH response to LH-RH, whereas it did not alter FSH response to LH-RH. These results suggest that SRIH may play a part in the regulation of LH secretion in normal women. PMID- 2875016 TI - Effects of vasoactive autacoids on different segments of human umbilicoplacental vessels. AB - Effects of serotonin, prostaglandin E2, prostaglandin F2 alpha, U 46619 (a thromboxane A2 mimetic) and angiotensin I and II on the perfusion pressure were studied on vessel segments from human umbilical arteries, placental arteries and the umbilical vein during in vitro perfusions. All drugs were found to induce vasoconstriction. Serotonin displayed strong vasoconstrictor potencies in all vessel segments, whereas the responsiveness to the other autacoids differed greatly in the various segments. In the umbilical artery prostanoids were most potent in the juxtafetal segment, whereas angiotensin I and II displayed greatest effects in the juxtaplacental segment. The results lend additional support to the concept that angiotensins and prostanoids are of importance in the regulation of fetal extracorporeal blood flow. PMID- 2875018 TI - External fixation of the foot and ankle. AB - The use of Hoffmann external fixation in the treatment of ankle and foot trauma in 26 patients is reviewed. There were 21 males and five females, ranging in age from 14 to 56 years. There were 22 fresh fractures and four arthrodeses. Fourteen of the 22 injuries were open fractures. Eight of 22 involved foot joint disruptions. This form of treatment required a complete set of external fixation equipment, sound knowledge of foot and ankle anatomy, and technical skill in frame construction and application. This fixateur allowed three plane stabilization of complex fractures, mobilization of unaffected joints, and access to wounds for soft tissue care. Follow-up evaluations from 24 to 48 months demonstrated good clinical results. The fractures healed and soft tissue and joint function were preserved. The arthrodeses fused. There were no neurovascular complications, pin tract infections, or equipment breakage. Foot trauma frequently combines soft tissue injury and complex skeletal instability, which makes external fixation particularly attractive. Although ideal indications for the use of this technique have not yet been determined, the theoretical advantages and initial results are encouraging. External fixation is a useful addition to the treatment armamentarium of the foot surgeon. PMID- 2875019 TI - [Eye symptoms in dystonic-hyperkinetic syndrome]. PMID- 2875020 TI - [Combined psychopharmacotherapy of endogenous depression. Adjuvant antidepressive drug treatment with benzodiazepines or neuroleptics: oxazolam versus chlorprothixene]. PMID- 2875021 TI - Treatment of pulmonary hypertension. AB - Reversible causes of pulmonary hypertension, such as mitral stenosis or pulmonary embolism, should be corrected causally. The therapy of pulmonary hypertension is difficult in those diseases where the causes or mechanisms are not understood or are unknown. In chronic obstructive lung disease, the primary objective is to improve airflow and alveolar ventilation (theophylline, beta-sympathicomimetics). Long-term oxygen (more than 18 hours a day) should be used in patients with paO2 below 55 mm Hg, since a reduction in pulmonary vascular resistance and a prolonged survival has been demonstrated. The role of vasodilator therapy (hydralazine, nitrates, diazoxide, captopril, calcium-blockers and others) in chronic obstructive lung disease remains uncertain. In primary pulmonary hypertension, a pulmonary vasodilator is recommended after demonstrating (for example with an infusion of prostaglandin I2), that the increased pulmonary vascular resistance is still reversible. The initiation of therapy should be performed cautiously under hemodynamic monitoring. PMID- 2875022 TI - Is there negative chronotropism via adrenergic alpha receptor in isolated rabbit atria? PMID- 2875023 TI - Insulin dependence of the actions of growth hormone and somatostatin on splanchnic biogenic amines of the dog. AB - It is known from studies previously conducted in this laboratory that an iv injection of ovine growth hormone (GH, 100 micrograms/kg BW) or an equimolar amount of somatostatin (SRIF, 7.5 micrograms/kg BW), given to normal conscious dogs into a saphenous vein, leads to a significant increase in hepatic portal plasma serotonin and a simultaneous decrease in the concentrations of dopamine, norepinephrine and epinephrine. The changes take place within 12 minutes after the injection and are observed only in the portal circulation. The purpose of the present experiment was to investigate whether or not similar results could be obtained in diabetic animals. Mongrel dogs were rendered diabetic by surgical pancreatectomy and fitted with an indwelling hepatic portal catheter. Radioenzymatic methods were employed for quantitative measurements of plasma free serotonin and catecholamines. No response was noted when the same type of experiments as those conducted in normal dogs were now carried out in trained, fully conscious totally pancreatectomized dogs deprived of exogenous insulin supply. When the same animals were given an injection into a peripheral vein of 50 mU/kg BW regular crystalline insulin (a small dose that affected neither plasma glucose nor biogenic amine levels) 10 minutes prior to the administration of the other hormones, the usual response to both GH and SRIF was restored, i.e. the data were comparable to those of normal dogs. It is concluded that the GH/SRIF effect on gut biogenic amines is insulin dependent. PMID- 2875024 TI - Effect of parathyroid hormone on plasma renin activity in humans. AB - The effect of PTH infusion on PRA was evaluated in 22 normotensive subjects. Intravenous infusion of PTH produced an increase in PRA in studied subjects. This increase in PRA was dose dependent from 1.505 +/- 0.226 to 2.500 +/- 0.346 nmol/l/hour after administration of 100 units of PTH and from 1.648 +/- 0.189 to 4.294 +/- 0.614 nmol/l/hour after 200 units of PTH and was markedly decreased by a beta blocking drug from 1.660 +/- 0.259 to 2.498 +/- 0.485 nmol/l/hour. These responses were observed without any significant changes in plasma calcium and blood pressure. From our results we can conclude that PTH increases PRA in normotensive controls. This effect is partly blocked by beta adrenergic blockers. PMID- 2875025 TI - Neurochemical basis of chemical thermoregulation and artificial hypobiosis. PMID- 2875026 TI - IL-2 receptor dysfunction and adult T-cell leukemia. PMID- 2875028 TI - [Activity and tolerance of a paracetamol-codeine combination compared to glafenine in post-operative pain in oral surgery]. PMID- 2875027 TI - Indomethacin-induced sialic acid-mediated changes in surface markers from "cortical type" to "medullary type" in murine thymoma line EL-4. AB - The effect of indomethacin (INDO), a specific inhibitor of prostaglandin (PG) synthesis, on the expression of markers during thymocyte differentiation such as Thy-1, H-2K, and peanut agglutinin (PNA) receptor was examined by immunofluorescence, using poorly differentiated thymoma, EL-4, as the indicator cells. EL-4 cells grown in the culture medium in the presence of INDO exhibited lower levels of Thy-1 and PNA, and a higher level of H-2K, compared with the EL-4 cells grown in medium without INDO. The decrease in PNA level by INDO was attributed to an increased density of sialic acid bound to PNA receptors on the cell surface, because treatment with neuraminidase (Nase) released more sialic acid from such cells, as compared with control cells, and markedly increased the detectable amounts of PNA receptors. On the other hand, a decrease of Thy-1 or an increase of H-2K may be ascribed to the decrease of Nase-resistant sialic acid on the cell surface, determined by analyses with FITC-LPA, sialic acid-specific lectin, and by metabolic labeling of surface sialic acid. These results suggest that the PG-system modulates the metabolism of sialic acid located on the thymocyte surface and alters the expression of surface markers of thymocytes. PMID- 2875029 TI - Nutritional relationships between oral bacteria. AB - Nutritional relationships were revealed during the coculturing of Bacteroides gingivalis with Wolinella recta and Bacteroides melaninogenicus with W. recta. W. recta produced a substance that stimulated the growth of B. gingivalis and B. melaninogenicus. Characterization by thin-layer chromatography and absorption spectrometry identified the compound as protoheme. Production of large amounts of formate by B. melaninogenicus stimulated the growth of W. recta. These nutritional relationships could represent examples of mechanisms favoring bacterial succession in periodontal sites. PMID- 2875030 TI - Receptor-binding function of type 1 pili effects bladder colonization by a clinical isolate of Escherichia coli. AB - The role of type 1 pili in promoting bladder colonization was examined by constructing two mutant strains of a clinical Escherichia coli isolate. One mutant was isogenic to the parental strain save for a lesion in a gene required for pilus receptor binding; the other mutant was isogenic save for a lesion in the gene encoding the pilus structural subunit. Using mixed infections of the parental and mutant strains in an ascending rat cystitis model, we found that type 1-piliated mutants that lacked the receptor-binding function were as ineffective in bladder colonization as were mutants lacking the entire organelle. PMID- 2875031 TI - The effect of salicylazosulphapyridine (sulphasalazine) on male fertility. A review. AB - Salicylazosulfapyridine (SASP), a drug used in the treatment of inflammatory bowel diseases, has been reported to depress the fertility in males. Therefore, some authors have proposed SASP as a new lead in the search for a contraceptive for men. Based on a review of the literature, our conclusion is that SASP taken in tolerable doses has not sufficient antifertility effect. Additionally, the drug has too serious and too many side effects to be accepted as a contraceptive. However, the effect on male fertility of other sulfa drugs and related compounds remains to be investigated. PMID- 2875032 TI - Cancer and the use of estrogens. AB - Although unopposed estrogen therapy, as well as persistent or increased endogenous estrogens, increases the risk for endometrial hyperplasia and cancer, added progestogen decreases the risk for adenocarcinoma of the endometrium to less than that observed in untreated women. The progestogen challenge test should be administered to all postmenopausal women with an intact uterus--including estrogen-treated postmenopausal women and those with sufficient endogenous estrogens to remain asymptomatic--and the progestogen continued for 13 days each month for as long as withdrawal bleeding results. Estrogen replacement therapy should not be withheld from postmenopausal women who are estrogen deficient, since there is no evidence that estrogens increase the risk for breast cancer. Progestogen added to estrogen replacement significantly reduces the risk for mammary malignancy; therefore, progestogens should be given, even to women who have had a hysterectomy, for 10 to 13 days each month whenever they are prescribed estrogen therapy. PMID- 2875033 TI - SEM observations of an IUD from a patient with Actinomyces-like organisms on papanicolaou smear. PMID- 2875034 TI - An update on DES in the field of reproduction. AB - The general consensus is that a DES daughter is about 35% less likely than a non DES-exposed woman of equivalent age and health to have a noneventful pregnancy. It is important to state that fertility rates refer to couples. The male partner is responsible for 40% to 50% of infertility problems. Age is also an important factor, and female fertility is known to decrease with age from the early 20s. These two factors receive little consideration in most articles. However, it can be said that if there are no marked congenital anomalies present in the cervix and the uterus, then the probability that a DES-exposed daughter will have a normal child is quite good. PMID- 2875036 TI - The physiology of menstruation and the corpus luteum function. PMID- 2875035 TI - Naproxen sodium for OB/GYN use, with special reference to pain states: a review. AB - The effectiveness of naproxen sodium and its parent compound, naproxen, has been assessed in the treatment of a variety of obstetric and gynecologic problems, particularly pain states. This article summarizes the literature on the efficacy of the naproxen compounds in treatment of the following conditions: primary and secondary dysmenorrhea, insertion of a contraceptive intrauterine device, suction curettage, postpartum pain, pelvic inflammatory disease, gynecologic surgery, menorrhagia, premature labor and menopause. The data from the studies compiled demonstrate the usefulness of naproxen sodium or naproxen as an effective analgesic in treating pain and inflammation associated with these conditions. PMID- 2875037 TI - The treatment of cervical factor with ethinyl estradiol and human menopausal gonadotropins. AB - Previously we have demonstrated that one can significantly improve the cervical factor in cases that have failed with conventional therapy by employing high doses of estrogen to stimulate the cervical mucus glands. The patients are concomitantly treated with human menopausal gonadotropins to stimulate ovulation, because of endogenous gonadotropin suppression by the estrogen. Monitoring of the hMG is accomplished by pelvic sonography. Unfortunately, the serum estradiol assay cannot also be used because it would measure not only endogenous estradiol but also exogenous estradiol from the conjugated estrogens employed. A modification of this technique is described wherein the estrogen now used is ethinyl estradiol. This estrogen has very little cross-reactivity in the 17-beta estradiol assay. Thus, both ultrasound and serum estradiol monitoring can be used, resulting in a safer and more effective technique. PMID- 2875038 TI - Stress and fertility: some modalities of investigation and treatment in couples with unexplained infertility in Dublin. AB - The role of stress in infertility, and its treatment, is reviewed in various groups of couples labeled "unexplained infertile." A simplified profile of stress markers based upon basal prolactin estimations and psychological measurements found infertile couples more stressed than fertile controls and revealed a sub group of women characterized as having significantly high psychological stress scores and intermittent elevations of prolactin (spikers). This group was effectively treated with a combination of clomiphene citrate and bromocriptine. However, attention to the failures as well as the successes suggests optimum benefit to the patients might involve not only provision of a good clinic ambiance and pharmacological preparations, but also relaxation therapies such as Autogenic Training, which significantly lowered psychological and biochemical stress marker scores. PMID- 2875039 TI - The present and future application of lasers to the treatment of endometriosis and infertility. AB - Conventional approaches to the treatment of endometriosis usually require major surgery, prolonged use of medications or both. The laser has provided an opportunity to treat mild and moderate endometriosis at the time of diagnosis at laparoscopy, thus avoiding delays in attempts to conceive. This review describes the current use of the CO2, argon and Nd:YAG lasers in the treatment of endometriosis. Potential and future uses of the free-electron laser (FEL) are also described. PMID- 2875040 TI - Role of inhibin in polycystic ovarian syndrome. AB - The possible role of inhibin in the etiology of polycystic ovarian syndrome (PCO) was studied. In rats PCO was induced by thiouracil and human chorionic gonadotropin (hCG). These animals were grouped under different treatment schedules: inhibin; antibodies to inhibin; ovine follicle stimulating hormone (FSH). In rats treated with antibodies to inhibin, there was a decrease in ovarian weight concomitant with specific increase in serum FSH levels. No changes in serum luteinizing hormone (LH) and prolactin levels were observed. However, testosterone levels were significantly decreased. Histological examination of the ovaries showed a marked arrest in the cyst formation with new growing follicles. In animals treated with inhibin, testosterone levels increased without any accompanying changes in ovarian weight. The circulating levels of prolactin and LH were unaffected. A decrease in serum FSH levels was accompanied by an increase in the number of cysts. The study corroborates the hypothesis that inhibin is involved in the development of PCO syndrome. Hence, an antagonist to inhibin may prove useful for the treatment of women with this condition. PMID- 2875041 TI - The role of ultrasound in ovulation induction by gonadotropins. AB - Fifty anovulatory women were selected for treatment with gonadotropins. Sixty five were monitored by serum 17-beta estradiol (E2) levels and human chorionic gonadotropin was administered accordingly. Retrospective evaluation of cycles indicates that the overstimulation syndrome and the number of undesired multiple pregnancies can be reduced after both ovaries have been visualized by ultrasound if, regardless of E2 serum levels, human chorionic gonadotropin is administered when one or two mature follicles are seen and withheld when three or more mature follicles are seen. PMID- 2875042 TI - The impact of in vitro fertilization on the practice of gynecology and obstetrics. AB - Contemporary programs of in vitro fertilization (IVF) approach a pregnancy rate per cycle which is comparable to the pregnancy rate per month of exposure in normal reproduction. IVF has changed the approach to several pelvic conditions. Because multiple concepti are usually transferred in a program of IVF, and since 40% of implanted sites were found to vanish, it is necessary to be exceedingly careful in applying the usual clinical criteria for completion of an abortion for fear that the surgical interference will terminate a residual viable site. Because of the potential for rupture at the cornu during pregnancy, IVF has led to a reevaluation of the technique of salpingectomy. The indications for various types of tubal surgery must be reconsidered so that patients may be offered IVF if the expectancy from tubal surgery is inferior to that from IVF. This is especially true for repetitive tubal surgery, in which the subsequent pregnancy rate seems to be only about 5%, except in special circumstances. The retention of the tube in patients with ectopic pregnancy should be reevaluated in the light of contemporary figures of the expectancy of pregnancy after such an operation compared with the expectancy of pregnancy in patients who have had bilateral salpingectomies in programs of IVF. Some patients with endometriosis who have failed other types of therapy have become pregnant with IVF. In view of a satisfactory pregnancy rate with IVF in patients in the age group 35-39, it is possible that IVF should be offered as a primary therapy for patients in this age bracket with mild or moderate endometriosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875043 TI - Neuroleptic-opioid interaction: relevance to tardive dyskinesia. PMID- 2875044 TI - [Opioids and the occurrence of pain]. PMID- 2875045 TI - Lebanon--its effect on smoking and drinking habits among Irish United Nations troops. PMID- 2875046 TI - The distribution of sympathetic adrenergic, tyrosine hydroxylase- and neuropeptide Y-immunoreactive nerves in human axillary sweat glands. AB - The innervation of human axillary sweat glands was studied by using the specific SPG (sucrose-potassium phosphate-glyoxylic acid) catecholamine histofluorescence method and the peroxidase-antiperoxidase (PAP) immunocytochemical method. The present results demonstrated that human sweat glands are surrounded by nerves containing a weak tyrosine hydroxylase activity. Nerves showing catecholamine histofluorescence could be visualized around the sweat glands only in the presence of exogenous catecholamine (adrenaline in the local anestheticum). In all tissue specimens studied fluorescent adrenergic nerves could be seen around arteries and arterioles corresponding to the distribution of neuropeptide Y-like immunoreactive nerves. PMID- 2875048 TI - Effect of misonidazole on neurotransmitter systems. AB - This study examines the effect of chronic administration of misonidazole on four neurotransmitter pathways (norepinephrine, dopamine, acetylcholine, and GABA) of the central nervous system (CNS). Biochemical assays examined the neurotransmitter synthesizing enzymes tyrosine hydroxylase (TOH) for catecholamines and choline acetyltransferase (CAT) for acetylcholine. An immunocytochemical stain for glutamic acid decarboxylase (GAD) was used as an enzymatic marker for GABAergic neurons. In drug-treated mice, enzymatic activity for TOH as well as the total concentration of enzyme was significantly increased in the locus coeruleus (LC), a principal norepinephrine-containing nucleus of the brainstem, but not in other brain regions. Correlative histofluorescence examination of the LC also showed an increase in the fluorescence intensity of noradrenergic neurons of the nucleus. In contrast, CAT activity was not different from controls in any of the areas examined. In the brainstem, immunocytochemical staining for GAD showed a significant reduction in the number of immunoreactive varicosities juxtaposed to neurons of the lateral vestibular nucleus suggestive of a loss of afferent GABAergic input from the cerebellum. These data suggest that both norepinephrine and GABAergic systems may be altered in selective nuclei of the CNS by chronic administration of misonidazole, and that drug related changes in NE and GABA may underline some of the neurotoxic side effects of MISO and/or exacerbate a patient's pre-existing cardiovascular or neurological problems. PMID- 2875047 TI - A combined light and electron microscopic immunocytochemical method for the simultaneous localization of multiple tissue antigens. Tyrosine hydroxylase immunoreactive innervation of corticotropin releasing factor synthesizing neurons in the paraventricular nucleus of the rat. AB - In order to study the morphological interrelationships between immunocytochemically identified neuronal systems, a double labelling procedure - suitable for correlative light and electron microscopic observations - is introduced. The technique is based on the consecutive use of the silver-gold (SG) intensified and non-intensified forms of the oxidized 3,3'-diaminobenzidine (DAB) chromogen in the framework of the peroxidase-antiperoxidase complex (PAP) indirect immunocytochemical procedure. The first tissue antigen is detected by the SG intensified DAB chromogen, which has a black color and high electron density. The structures containing the second antigen are visualized by the non intensified DAB-endproduct, which is less electron-dense than the silver-gold amplified form and is brown. The metallic shield that forms around the labeled antibody sequences associated with the first antigen prevents non-specific binding of immunoglobulins used for the detection of the second tissue antigen. The application of this method for the simultaneous detection of tyrosine hydroxylase (TH)- and corticotropin releasing factor (CRF)-immunoreactive structures revealed that black colored TH-immunopositive fibers contacted brown colored CRF-synthesizing neurons in the hypothalamic paraventricular nucleus. The juxtaposition of TH- and CRF-containing elements was apparent in both thick vibratome (40 micron) and semithin (1 micron) sections. At the ultrastructural level, TH-positive terminals - labeled by silver-gold grains - were observed to establish asymmetric synapses with both CRF- and TH-immunoreactive neurons. The former finding indicates a direct, TH-immunopositive, catecholaminergic influence upon the hypothalamic CRF system, while the latter demonstrates the existence of intrinsic connections between TH-positive elements. PMID- 2875049 TI - Salmonella: virulence factors and enteric salmonellosis. PMID- 2875050 TI - Comparison of the biological effects of phenobarbital and nafenopin on rat hepatocarcinogenesis. AB - In order to further analyze the biological effects of phenobarbital (PB) and nafenopin (NAF) on rat hepatocarcinogenesis, four experiments were undertaken. In the first one, their "promoting" effect on an ongoing carcinogenic process was analyzed. Rats were initiated by diethylnitrosamine treatment (I) and submitted two weeks later to a selection procedure (S). One week after 2 acetylaminofluorene (2-AAF) release, the animals received for up to 56 weeks a basal diet or a diet containing 0.05% of PB or 0.1% of NAF. The quantitative analysis of the gamma-glutamyl-transferase-positive lesions showed that, 8 to 19 weeks after I, PB enhanced the development of preneoplastic lesions whereas NAF inhibited it as compared to a group receiving a basal diet. However, both compounds enhanced the incidence and the yield of liver cancer starting 27 weeks after I (67% and 95%, respectively, vs 10%). In the second experiment, the effect of chronic administration of PB and NAF given after I without S or after S without I was analyzed. Within a period of observation of 27 to 32 weeks, the incidence of cancer was 10% after I/PB and 75% after I/NAF. No cancer developed after S/PB, S/NAF or NAF alone. The third experiment was designed to test whether NAF had an initiating or selecting effect. The results of the quantitative analysis of the gamma-glutamyl-transferase-positive lesions showed that as compared to diethylnitrosamine, NAF had no initiating effect. When NAF replaced 2 AAF in the selection procedure, few gamma-glutamyl-transferase-positive lesions and no cancer were detected 8 and 32 weeks after I. The fourth experiment indicated that NAF could not prevent the remodeling of preneoplastic lesions induced in the I/S protocol. Even though they both have a "promoting" effect in liver carcinogenesis as evidenced by the increased incidence and yield of cancer, PB and NAF act differently. PMID- 2875051 TI - Scaled-up production and purification of Clostridium perfringens type A enterotoxin. AB - Methods for small-scale production of Clostridium perfringens type A enterotoxin were unsuitable for large-scale culture of this organism. Rapid, efficient harvesting of 40 1 batch culture of Cl. perfringens was achieved by tangential flow micro-filtration with the Millipore Pellicon cassette system. Enterotoxin containing extracts were prepared by passing concentrated suspensions of the harvested cells through a French pressure cell. The overall yield of purified enterotoxin was 38.8%. The toxin gave a single band on native polyacrylamide gels but formed high molecular weight aggregates in the presence of sodium dodecyl sulphate. These aggregates frequently occurred during storage of non-sterile enterotoxin preparations but could be separated from the monomer toxin by gel filtration on Sephadex G-100. Purified monomer enterotoxin had biological activities of 119.3 micrograms/kg mouse lethal dose when injected intraperitoneally and 3333 capillary permeability increasing units/mg protein in guinea pig skin. Thirty micrograms of the enterotoxin caused fluid accumulation in ligated rabbit ileal loops. Aggregated enterotoxin had no demonstrable biological or immunological activity. PMID- 2875052 TI - The carrier state: Bordetella pertussis. PMID- 2875053 TI - beta-Blockade used in precision sports: effect on pistol shooting performance. AB - In a double-blind cross-over study of 33 marksmen (standard pistol, 25 m) the adrenergic beta 1-receptor blocker, metoprolol, was compared to placebo. Metoprolol obviously improved the pistol shooting performance compared with placebo. Shooting improved by 13.4% of possible improvement (i.e., 600 points minus actual points obtained) as an average (SE = 4%, 2P less than 0.002). The most skilled athletes demonstrated the clearest metoprolol improvement. We found no correlation between the shooting improvement and changes in the cardiovascular variables (i.e., changes of heart rate and systolic blood pressure) and no correlation to the estimated maximum O2 uptake. The shooting improvement is an effect of metoprolol on hand tremor. Emotional increase of heart rate and systolic blood pressure seem to be a beta 1-receptor phenomenon. PMID- 2875054 TI - Endogenous modulation of alpha-adrenergic contraction in canine tracheal muscle. AB - We studied the effect of passive stretch on the contraction of canine tracheal smooth muscle (TSM) to alpha-adrenergic agonists and acetylcholine (ACh) in 211 epithelium-free TSM strips from 42 dogs in vitro. Passive stretch at a resting tension of 100 g/cm2 caused a time-dependent decrease in the contractile response to alpha-adrenergic agonists after beta-adrenergic blockade with propranolol. Initial contraction elicited by 10(-3) M phenylephrine (PE) and clonidine (CLO) decreased at 2 h by 31 and 100%, respectively. Decrease in alpha-adrenergic contractility did not result from tachyphylaxis; no contraction was elicited by PE or CLO given for the first time after 4-h passive stretch at 100 g/cm2. The TSM response to ACh was unchanged over the same time in the same strips. When TSM strips were incubated at zero resting tension for 6 h, some attenuation of the alpha-adrenergic contractile still occurred but was not substantial. Similarly, when strips were incubated with 10(-6) M indomethacin (INDO) or 10(-5) M mefenamic acid (MEF) at 100 g/cm2 resting tension, time-dependent attenuation of the response to PE and CLO was reduced for at least 6 h, and initial contraction elicited by PE was augmented. Response of TSM to ACh was not affected by prostaglandin synthetase inhibition with INDO. We conclude that passive stretch of canine TSM in vitro leads to decreased responsiveness to alpha-adrenergic stimulation that can be prevented with INDO or MEF. These data are consistent with the synthesis of an inhibitory eicosanoid in epithelium-free canine TSM that may be activated by mechanical deformation of the muscle. PMID- 2875055 TI - Synthesis of surfactant-associated protein, 35,000 daltons, in fetal lung. AB - The major human pulmonary surfactant-associated protein of 35,000 daltons (Da) (SAP-35), consists of a group of related proteins of 27,000-36,000 Da, with isoelectric points ranging from pH 4.6 to 5.2. SAP-35 precursors were identified by immunoprecipitation of protein products of in vitro translation of normal adult human poly(A)+ mRNA with human SAP-35 antiserum. The translation products nearly comigrated with the most basic components of alveolar SAP-35 (mol mass = 24,500-27,000 Da). Processing of the primary translation products by canine pancreatic microsomal membranes increased their apparent molecular weight to 29,000-30,000-Da forms, which were sensitive to endoglycosidase F, suggesting the addition of asparagine-linked oligosaccharides to the molecules. A smaller protein of 24,500 Da was generated during treatment with canine microsomal membranes likely representing cleavage of a signal peptide. SAP-35 was not detected in explants of [35S]methionine-labeled fetal lung (20-24 wk gestation) after 1 day of culture or immunoprecipitates of in vitro translated poly(A)+ mRNA isolated from fetal human lung. However, after 3-5 days of organ culture, synthesis of SAP-35 was readily detected by immunoprecipitation of [35S] methionine-labeled tissue. Fully sialylated (neuraminidase-sensitive forms) comigrated with fully glycosylated SAP-35 isolated from human surfactant. High mannose (endoglycosidase H-sensitive precursors) were also synthesized by the organ cultures and were distinct from the secreted form in surfactant. Synthesis of surfactant-associated SAP-35 and its precursors was induced in association with morphological maturation of the type II epithelial cell during organ culture of human fetal lung. PMID- 2875056 TI - Effect of nicotine and acetylcholine on crustacean muscle membrane potential. AB - We have investigated the effect of nicotine and acetylcholine on the resting membrane potential of the crayfish extensor muscle in order to determine whether crustacean muscle can be activated by cholinergic compounds. Intracellular recordings from individual deep extensor abdominal muscle cells were made using standard glass microelectrode techniques. The resting membrane potential was measured before and after treatment with glutamate, nicotine, and acetylcholine. Glutamate, which is a known activator of crayfish muscle, was used to determine whether the muscle cell preparation was viable and capable of responding to any of the test substances. Our results confirm that application of glutamate is associated with a depolarization of the muscle membrane. However, muscle cells showed no depolarization after treatment with nicotine (50 microM) or acetylcholine (66 microM). These results argue against the notion that increases in muscle tension may be responsible for the increased receptor organ discharge observed in the presence of nicotine. Rather, it supports the hypothesis that nicotine is acting directly on the mechanoreceptor membrane to change its sensitivity. PMID- 2875057 TI - Gas chromatographic determination of histapyrrodine hydrochloride in pharmaceutical preparations. AB - A simple gas chromatographic method is described for the determination of histapyrrodine HCl in marketed formulations. Chlorpheniramine maleate is used as the internal standard. The amount of histapyrrodine HCl found by the proposed method averaged 19.91 mg/tablet, compared with the label claim of 20 mg/tablet. The method was statistically evaluated for accuracy and precision. PMID- 2875058 TI - Spectrophotometric and liquid chromatographic identification of 3,4 methylenedioxyphenylisopropylamine and its N-methyl and N-ethyl homologs. AB - 3,4-Methylenedioxyphenylisopropylamine (MDA) is an hallucinogenic drug that somewhat resembles lysergic acid diethylamide (LSD) in its effects. Recently, widespread abuse of the N-methyl homolog (MDMA) of MDA has led to federal control. This article reports on the synthesis of the N-ethyl homolog (MDEA) of MDA as well as spectrophotometric and chromatographic methods for identification of the 3 homologs. PMID- 2875059 TI - Twice-daily beclomethasone dipropionate in the treatment of childhood asthma. AB - Chronic nonsteroid-dependent childhood asthma was treated by adding beclomethasone dipropionate (BDP) or placebo (P) to the daily regimen of theophylline (T). Subjects (6-12 years) were selected based on daily control of asthma by T at necessary T levels in sera of 10-20 micrograms. Active BDP (200 micrograms b.i.d.) and P groups were randomly assigned. Each subject's baseline values were evaluated on a 4-week open phase followed by a 10-12 week double blind phase. Daily diaries were kept for signs, symptoms, Wright peak flow recordings, and medication requirements. Visits were monitored for urine and serum cortisols, pulmonary function tests (PFT), objective changes, and medication compliance. Demographics between both groups were nonsignificant (NS). Baseline PFTs in P group were significantly better than the BDP group. Serum and urine cortisols and ACTH responses were NS (p less than 0.05). Drug efficacy for asthma characteristics was significantly improved in the BDP group (p less than 0.05) only. The BDP group maximized their response by 8 weeks, with improvement of their FEV1 and FEF25-75 PFT. Thus, b.i.d. BDP provided good asthma control and the twice-daily program should insure improved compliance. PMID- 2875060 TI - Transglycosylase and endopeptidase participate in the degradation of murein during autolysis of Escherichia coli. AB - The cell wall degradation products released from Escherichia coli during autolysis triggered by cephaloridine or trichloroacetic acid were isolated and characterized. Murein was selectively lost from the disaccharide tetrapeptides and the bisdisaccharide tetrapeptide components. Two major autolytic products accounted for more than 85% of the released material. Compound 1 (60 to 80% of released material) was a disaccharide tetrapeptide monomer containing a 1,6 anhydromuramic acid residue. Compound 2 (15 to 30% of released material) was a mixture of a tritripeptide and a tritetrapeptide without hexosamines. Taken together the findings suggest that autolytic cell wall degradation in E. coli is selective and involves the activity of both the hydrolytic transglycosylase and an endopeptidase. Upon release, at least some of the wall components were also exposed to the activity of the N-acetylmuramic acid-L-alanine amidase. PMID- 2875061 TI - Cloning of chromosomal DNA encoding the F41 adhesin of enterotoxigenic Escherichia coli and genetic homology between adhesins F41 and K88. AB - The genetic determinant for production of the adhesive antigen F41 was isolated from a porcine enterotoxigenic Escherichia coli strain by cosmid cloning. The cloned DNA included sequences homologous to those of hybridization probes prepared from the K88 adhesive antigen operon. Transposon insertions which inactivated F41 production mapped to the same region of DNA showing homology with the K88 genes, demonstrating the genetic relatedness of F41 and K88. Hybridization of a K88 gene probe to plasmid and total DNA from the porcine E. coli isolate from which the F41 gene was cloned indicated that F41 is chromosomally encoded by this strain. This observation was extended to other F41 producing animal isolates. A large number of animal E. coli isolates were examined with K88, F41, and K99 gene probes and for mannose-resistant hemagglutination of human group O erythrocytes and K88 and F41 antigen production. All K88 and F41 antigen producers possessed genetic homology with the K88 and F41 gene probes. Most, but not all, F41-producing strains possessed homology to the K99 gene probe, reflecting the previously observed association of F41 and K99 antigen production. In the strains examined, homology with the K99 gene probe was plasmid associated, whereas homology with the F41 gene probe was chromosomal. The K88 antigen-producing strains showed no homology with the K99 probe. A number of strains possessed homology with the K88 and F41 gene probes and were mannose-resistant hemagglutination positive, but did not produce K88 or F41 antigens. This suggests that there are adhesins among animal isolates of E. coli which are genetically related to but antigenically distinct from K88 and F41. PMID- 2875062 TI - Helical structure of Bordetella pertussis fimbriae. AB - The helical structures of Bordetella pertussis fimbriae of serotypes 2 and 6 were determined by optical diffraction analysis of electron micrographs of negatively stained paracrystalline bundles of purified fimbriae. The fimbrial structure is based on an axial repeat of 13 nm that contains five repeating units in two complete turns of a single-start helix. This structure was confirmed by direct measurements of mass per unit length for individual fimbriae performed by dark field scanning transmission electron microscopy of unstained specimens. These data further established that the helically repeating unit is a monomer of fimbrial protein (Mr congruent to 22,000 for type 2 and Mr congruent to 21,500 for type 6). Radial density profiles calculated from the scanning transmission electron micrographs showed that the fimbria has peak density at its center, i.e., no axial channel, consistent with the results of conventional negative staining electron microscopy. The radial profile gives an outermost diameter of approximately 7.5 nm, although the peripheral density is, on average, diffuse, allowing sufficient intercalation between adjacent fimbriae to give a center-to center spacing of approximately 5.5 nm in the paracrystals. Despite serological and biochemical differences between type 2 and type 6 fimbriae, the packing arrangements of their fimbrial subunits are identical. From this observation, we infer that the respective subunits may have in common conserved regions whose packing dictates the helical geometry of the fimbria. It is plausible that a similar mechanism may underlie the phenomenon of phase variations in other systems of bacterial fimbriae. PMID- 2875063 TI - Pharmacologic treatment of phobic disorders. AB - Pharmacologic treatment of phobic disorders, in particular agoraphobia, has been proved to be effective, especially when used in combination with behavior therapy. Favorable responses to tricyclic antidepressants, monoamine oxidase inhibitors, and benzodiazepines have been reported. The limitations of drug therapy for phobias include high dropout rates and the tendency to relapse after discontinuation of therapy. Successful treatment depends on the careful selection of patients and medications and on coordination of drug and behavior therapies. PMID- 2875064 TI - Effect of alprazolam and diazepam on anxiety and panic attacks in panic disorder: a controlled study. AB - Forty-eight patients currently experiencing panic attacks were randomly assigned to double-blind treatment with alprazolam, diazepam, or placebo. Efficacy was assessed using the Hamilton Rating Scale for Anxiety and a panic attack frequency rating scale. Results indicate that the two active treatments appeared equally effective in reducing both the frequency of panic attacks and the severity of generalized anxiety when compared with placebo. Overall, these data support the use of benzodiazepines in the treatment of panic disorder. PMID- 2875065 TI - Tremor and tardive dyskinesia. AB - A retrospective review of charts for the prevalence of tremor in patients with tardive dyskinesia revealed that 10% of 232 patients with a diagnosis of tardive dyskinesia also had parkinson-like tremor. No demographic or clinical risk factors for this tremor could be identified. The body areas affected by tremor are described, and it is suggested that tremor occurring in areas other than the wrist may pose a problem in differential diagnosis of patients with tardive dyskinesia. Changes in tremor and tardive dyskinesia after alterations in medication dose are reported, and recommendations for management are given. PMID- 2875066 TI - Psychotropic blood levels: a guide to clinical response. AB - In the clinical use of psychotropic drugs, the value of blood level monitoring remains uncertain because, for most of these agents, consistent, predictable correlations between blood level and therapeutic response have not been established. In recent years productive work has been done in this area which suggests that, in certain clinical situations and with certain psychotropic agents, monitoring of blood levels may be a useful component of patient care. The literature regarding blood levels and therapeutic response to various psychotropic drugs is reviewed and some of the clinical settings in which blood levels are, in fact, predictive of therapeutic response in the management of psychiatric illness are discussed. PMID- 2875067 TI - Determination of bioequivalence of psychotropic drugs and concerns involving product interchange. AB - There is a growing debate among researchers and practitioners concerning the validity of the Food and Drug Administration (FDA) standards for establishing generic interchange through assignment of "therapeutically equivalent" designations for noninnovator or generic drugs. This debate has particular significance for psychotropic drugs which are used in the management of patients with severely debilitating mental diseases. Thus, the controversy primarily focuses on the appropriateness of using the FDA's therapeutic equivalence designation as a criterion for interchange. This is particularly important in light of the lack of well-defined standards for bioequivalence studies and in view of the effect of mandatory substitution laws and financial incentives that encourage generic dispensing that can lead to frequent and indiscriminate interchange among multiple generic brands. Specific concerns include the validity of assay techniques for drug in biologic fluids, statistical power analysis, the appropriateness of the "70/70 rule," and the relevance of studies carried out in healthy normal volunteers in the determination of bioequivalence. PMID- 2875068 TI - Finding of a KCl-independent, electrogenic, and ATP-driven H+-pumping activity in rat light gastric membranes and its effect on the membrane K+ transport activity. AB - Resting rat light gastric membranes prepared through 2H2O and Percoll gradient centrifugations were enriched not only with (H+-K+)-ATPase and K+ transport activity (Im, W. B., Blakeman, D. P., and Davis, J. P. (1985) J. Biol. Chem. 260, 9452-9460), but also with a K+-independent, ATP-dependent H+-pumping activity. This intravesicular acidification has been ascribed to an oligomycin-insensitive H+-ATPase which differed from (H+-K+)-ATPase in several respects. The H+-ATPase is electrogenic, apparently of lower capacity, required a lower optimal ATP concentration (4 microM for the H+-ATPase and 500 microM for (H+-K+)-ATPase), of lower sensitivity to vanadate and sulfhydryl agents such as p chloromercuribenzoate and N-ethylmaleimide, and insensitive to SCH 28,080, a known competitive inhibitor of (H+-K+)-ATPase with respect to K+. Operation of the H+-ATPase, however, appeared to interfere with the K+ transport activity in the light gastric membranes, probably through development of intravesicular positive membrane potential; for example, micromolar levels of Mg2+-ATP fully inhibited K+ uptake and stimulated K+ efflux as measured with 86Rb+. Involvement of (H+-K+)-ATPase in the K+ transport is not likely, since the inhibitory effect of Mg2+-ATP continued even after removal of the nucleotide with an ATP-scavenging system. Moreover, nigericin, an electroneutral H+/K+ exchanger, could bypass the inhibitory effect of Mg2+-ATP and equilibrate the membrane vesicles with 86Rb+ while valinomycin, an electrogenic K+ ionophore, could not. Finally, the H+ ATPase could possibly be involved in the acid secretory process, since its H+ pumping activity was removed from the light gastric membrane fraction upon carbachol treatment, along with the K+ transport and (H+-K+)-ATPase activities. We have speculated that the H+-ATPase is responsible for maintaining the K+ permeable intracellular membrane vesicles acidic and K+ free during the resting state of acid secretion and may contribute to basal acid secretion. PMID- 2875070 TI - The rate of import and assembly of F1-ATPase in Saccharomyces cerevisiae. AB - Subunit specific antiserum can be employed to study the course of ATPase assembly in mitochondria isolated from bakers' yeast. Comparing rates of subunit import with rates of enzyme assembly indicated that no substantial pool of unassembled subunits exists for the three largest ATPase peptides (alpha, beta, and gamma). Blocking import of specific ATPase subunits, however, did reveal a possible accumulation of unassembled alpha and gamma subunits in isolated mitochondria. The kinetic experiments also revealed a lag in the import of beta subunit relative to the uptake of alpha and gamma precursors. Experiments conducted in yeast cells confirmed that beta subunit is assembled soon after it is imported, but did not indicate a delay in import relative to the other subunits of F1. PMID- 2875069 TI - Enhancement of adenylate cyclase activity in S49 lymphoma cells by phorbol esters. Withdrawal of GTP-dependent inhibition. AB - 12-O-Tetradecanoylphorbol-13-acetate (TPA) enhances the apparent maximal velocity of adenylate cyclase in S49 lymphoma cells, an effect that seems not to result from an increased rate of activation of the catalytic subunit by the stimulatory GTP-binding protein (Gs) (Bell, J. D., Buxton, I. L. O., and Brunton, L. L. (1985) J. Biol. Chem. 260, 2625-2628). In membranes from wild type S49 cells, this enhancing effect of TPA is largely GTP-dependent; TPA enhances forskolin stimulated adenylate cyclase activity by 35% in the presence of guanine nucleotide but only slightly (approximately 10%) in its absence. TPA causes comparable results in membranes from the cyc- variant that lacks the GTP-binding subunit of Gs. Blockade of the activity of the inhibitory GTP-binding protein (Gi) by high concentrations of Mg2+ (100 mM) or Mn2+ (3 mM) abolishes the effect of TPA to enhance adenylate cyclase activity in wild type membranes. The potentiation by TPA of cAMP accumulation in intact cells is greater than and not additive with the similar effect of pertussis toxin (an agent known to abolish hormonal inhibition of adenylate cyclase). Kinetic experiments indicate that TPA decreases the rate of activation of Gi by guanine nucleotide. We conclude that the resultant withdrawal of tonic inhibition of adenylate cyclase is one mechanism by which phorbol esters enhance guanine nucleotide-dependent cAMP synthesis. PMID- 2875071 TI - The systematic characterization by aqueous column chromatography of solutes which affect protein stability. AB - We have systematically characterized, by aqueous column chromatography on a size exclusion cross-linked dextran gel (Sephadex G-10), 12 solutes, 11 of which are known to affect protein stability. Six are chaotropes (water structure breakers) and destabilize proteins, while five are polar kosmotropes (polar water structure makers) and stabilize proteins. Analysis of the chromatographic behavior of these neutral (ethylene glycol, urea), positively charged (Tris, guanidine, as the hydrochloride salts) and negatively charged (SO2-4, HPO2-4, F-, Cl-, Br-, Cl3CCO 2, I-, SCN-, as the sodium salts, in order of elution) solutes at pH 7 as a function of sample concentration (up to 0.6 M), supporting electrolyte, and temperature yields four conclusions, based largely on the behavior of the anions. Chaotropes adsorb to the gel according to their position in the Hofmeister series, with the most chaotropic species adsorbing most strongly. ++Chaotropes adsorb to the gel less strongly in the presence of chaotropes (a salting in effect) and more strongly in the presence of polar kosmotropes (a salting out effect). Polar kosmotropes do not adsorb to the gel, and are sieved through the gel according to their position in the Hofmeister series, with the most kosmotropic species having the largest relative hydrodynamic radii. The hydrodynamic radii of polar kosmotropes is increased by chaotropes and decreased by polar kosmotropes. These results suggest that a chaotrope interacts with the first layer of immediately adjacent water molecules somewhat less strongly than would bulk water in its place; a polar kosmotrope, more strongly. PMID- 2875073 TI - Adenine nucleotide-binding sites on beef heart F1-ATPase. Conditions that affect occupancy of catalytic and noncatalytic sites. AB - Beef heart mitochondrial F1 contains a total of six adenine nucleotide-binding sites including at least two different types of sites. Three "exchangeable" sites exchange rapidly during hydrolysis of MgATP, whereas three "nonexchangeable" sites do not (Cross, R. L. and Nalin, C. M. (1982) J. Biol. Chem. 257, 2874 2881). When F1 that has been stored as a suspension in (NH4)2SO4/ATP/EDTA/sucrose/Tris, pH 8.0, is pelleted, rinsed with (NH4)2SO4, dissolved, and desalted, it retains three bound adenine nucleotides. We find that two of these endogenous nucleotides are bound at nonexchangeable sites and one at an exchangeable site. The vacant nonexchangeable site is highly specific for adenine nucleotide and is rapidly filled by ADP upon addition of ADP or during ATP hydrolysis. ADP bound at this site can be removed by reprecipitating the enzyme with (NH4)2SO4. The single nucleotide retained by desalted F1 at an exchangeable site is displaced during hydrolysis of ATP, GTP, or ITP. The binding of PPi at two sites on the enzyme also promotes its dissociation. Neither procedure affects retention of nucleotide at the nonexchangeable sites. These observations, combined with the finding that PPi is much more easily removed from exchangeable sites than ADP, have led to the development of a procedure for preparing F1 with uniform and well-defined nucleotide site occupancy. This involves sequential exposure to MgATP, PPi, and high concentrations of Pi. Unbound ligand is removed between each step. The resulting enzyme, F1[3,0], has three occupied nonexchangeable sites and three vacant exchangeable sites. Evidence that nonexchangeable and exchangeable sites represent noncatalytic and catalytic sites, respectively, suggest that this form of the enzyme will prove useful in numerous applications, including transient kinetic measurements and affinity labeling of active site residues. PMID- 2875072 TI - Characterization of N-ethylmaleimide-sensitive proton pump in the rat kidney. Localization along the nephron. AB - This study is aimed both at characterizing an ATPase activity in rat kidney equivalent to the proton pump described in bovine kidney medulla and at localizing this enzyme along the nephron. Membrane fractions isolated from kidney homogenates by differential and density gradient centrifugations were enriched 7 fold in ATPase activity sensitive to N-ethylmaleimide (NEM). These fractions also displayed ATP-dependent proton transport. ATPase activity and proton transport in vesicles had similar pharmacological properties as both were insensitive to vanadate and ouabain and had similar sensitivities toward NEM (apparent Ki = 20 microM) and N,N'-dicyclohexylcarbodiimide (apparent Ki = 50 microM). Proton transport was dependent on chloride availability as chloride addition to the extravesicular medium stimulated proton transport in a dose-dependent fashion (apparent K 1/2 = 7 mM). NEM-sensitive ATPase activity displaying similar pharmacological properties as proton transport in vesicles was also found in single segments of nephron. It was insensitive to vanadate and ouabain, was inhibited by similar concentrations of NEM (apparent Ki = 15-20 microM) and N,N' dicyclohexylcarbodiimide (apparent Ki = 30 microM), and is therefore likely to be a proton pump. NEM-sensitive ATPase was localized in all the segments of the rat nephron; its activity was highest in proximal convoluted tubules; intermediate in proximal straight tubules, thick ascending limbs, and cortical collecting tubules; and lowest in outer medullary collecting tubules. PMID- 2875074 TI - Presence of a MgATP/ADP-dependent pp50 phosphatase in bovine brain coated vesicles. AB - Coated vesicles are involved in the intracellular transport of membrane proteins between a variety of membrane compartments in which they must be able to undergo repeated membrane fusion and fission. We previously described the presence of cyclic nucleotide- and Ca2+-independent protein kinase activity in bovine brain coated vesicles which specifically phosphorylated a unique Mr = 50,000 coated vesicle integral protein (pp50) on a threonine residue. We describe now the presence in bovine brain coated vesicles of the antagonistic enzymatic activity which dephosphorylates pp50. This phosphoprotein phosphatase occurs under two interconvertible active and inactive forms. The activation process needs the simultaneous presence of Mg2+ and ATP or ADP. Unchelated ATP, but not unchelated ADP, inactivates the pp50 phosphatase. The latter is associated with the vesicular core. MgADP activation of the pp50 phosphatase implicates a different mechanism which does not need a phosphorylated intermediate. Thus, the pp50 phosphatase might belong to a new phosphatase type distinct from the four other classes of well known protein phosphatases. PMID- 2875075 TI - Characterization of the subunit structure of the maize tonoplast ATPase. Immunological and inhibitor binding studies. AB - Gradient purified preparations of the maize 400-kDa tonoplast ATPase are enriched in two major polypeptides, 72 and 62 kDa. Polyclonal antibodies were prepared against these two putative subunits after elution from sodium dodecyl sulfate polyacrylamide gel electrophoresis gel slices and against the solubilized native enzyme. Antibodies to both the 72- and 62-kDa polypeptides cross-reacted with similar bands on immunoblots of a tonoplast-enriched fraction from barley, while only the 72-kDa antibodies cross-reacted with tonoplast and tonoplast ATPase preparations from Neurospora. Antibodies to the 72-kDa polypeptide and the native enzyme both strongly inhibited enzyme activity, but the 62-kDa antibody was without effect. The identity and function of the subunits was further probed using radiolabeled covalent inhibitors of the tonoplast ATPase, 7-chloro-4 nitro[14C]benzo-2-oxa-1,3-diazole ([14C]NBD-Cl) and N,N' [14C]dicyclohexylcarbodiimide ([14C]DCCD). [14C]NBD-Cl preferentially labeled the 72-kDa polypeptide, and labeling was prevented by ATP. [14C]DCCD, an inhibitor of the proton channel portion of the mitochondrial ATPase, bound to a 16-kDa polypeptide. Venturicidin blocked binding to the mitochondrial 8-kDa polypeptide but did not affect binding to the tonoplast 16-kDa polypeptide. Taken together, the results implicate the 72-kDa polypeptide as the catalytic subunit of the tonoplast ATPase. The DCCD-binding 16-kDa polypeptide may comprise the proton channel. The presence of nucleotide-binding sites on the 62-kDa polypeptide suggests that it may function as a regulatory subunit. PMID- 2875076 TI - The membrane ATPase of alkalophilic Bacillus firmus RAB is an F1-type ATPase. AB - At the optimal pH for growth (pH 10.5), alkalophilic Bacillus firmus RAB, an obligate aerobe, exhibits normal rates of oxidative phosphorylation despite the low transmembrane proton electrochemical gradient, about -60 mV (delta psi = -180 mV and delta pH = +120 mV). This bioenergetic problem might be resolved by use of an Na+ coupled ATP synthase; otherwise an F1F0-ATPase must be able to utilize low driving forces in this organism. The ATPase activity was extracted from everted membrane vesicles by low ionic strength treatment and purified to homogeneity by hydrophobic interaction chromatography and sucrose density gradient centrifugation. The ATPase preparation had the characteristic F1-ATPase subunit structure, with Mr values of 51,500 (alpha), 48,900 (beta), 34,400 (gamma), 23,300 (delta), and 14,500 (epsilon); the identity of the alpha and beta subunits was confirmed by immunoblotting with anti-beta of Escherichia coli and anti-B. firmus RAB F1. Methanol and octyl glucoside, agents that stimulated the low basal membrane ATPase activity 10- to 12-fold, dramatically elevated the MgATPase activity of the purified F1, more than 150-fold, to 50 mumol min-1 mg protein-1. Anti-F1 inhibited membrane ATPase activity greater than or equal to 80%. The membranes exhibited no Na+-stimulated or vanadate-sensitive ATPase activity when prepared in the absence or presence of Na+ or ATP. These findings, which are consistent with previous studies, establish that in alkalophilic bacteria, ATP hydrolysis, and presumably ATP synthesis is catalyzed by an F1F0-ATPase rather than a Na+ ATPase. PMID- 2875077 TI - Ultrastructural immunolocalization of lysyl oxidase in vascular connective tissue. AB - The localization of lysyl oxidase was examined in calf and rat aortic connective tissue at the ultrastructural level using polyclonal chicken anti-lysyl oxidase and gold conjugated rabbit anti-chicken immunoglobulin G to identify immunoreactive sites. Electron microscopy of calf aortic specimens revealed discrete gold deposits at the interface between extracellular bundles of amorphous elastin and the microfibrils circumferentially surrounding these bundles. The antibody did not react with microfibrils which were distant from the interface with elastin. There was negligible deposition of gold within the bundles of amorphous elastin and those few deposits seen at these sites appeared to be associated with strands of microfibrils. Lysyl oxidase was similarly localized in newborn rat aorta at the interface between microfibrils and nascent elastin fibers. Gold deposits were not seen in association with extracellular collagen fibers even after collagen-associated proteoglycans had been degraded by chondroitinase ABC. However, the antibody did recognize collagen-bound lysyl oxidase in collagen fibers prepared from purified collagen to which the enzyme had been added in vitro. No reaction product was seen if the anti-lysyl oxidase was preadsorbed with purified lysyl oxidase illustrating the specificity of the antibody probe. The present results are consistent with a model of elastogenesis predicting the radial growth of the elastin fiber by the deposition and crosslinking of tropoelastin units at the fiber-microfibril interface. PMID- 2875078 TI - Cloning and characterization of human and rat liver cDNAs coding for a gap junction protein. AB - An extended synthetic oligonucleotide (58-mer) has been used to identify and characterize a human liver gap junction cDNA. The cDNA is 1,574 bases long and contains the entire coding region for a gap junction protein. In vitro translation of the RNA products of this cDNA is consistent with it coding for a 32,022-D protein. Southern blot analysis indicates that the gap junction gene is present as a single copy, and that it can be detected in a variety of organisms using the human liver cDNA as a probe. The human cDNA has been used to screen a rat liver cDNA library, and a rat liver junction cDNA clone has been isolated. The rat liver clone is 1,127 bases in length, and it has strong sequence homology to the human cDNA in the protein-coding region, but less extensive homology in the 3'-untranslated region. PMID- 2875080 TI - New sensitive high-performance liquid chromatographic method for p-tyrosine aminotransferase assay. AB - A rapid, sensitive and specific procedure has been developed for the determination of p-tyrosine aminotransaminase activity. The assay is based on high-performance liquid chromatography (HPLC) separation and electrochemical detection of the pyruvate product, which has been derivatized with hydroxylamine to form a stable oxime. Using this method the product at the low pmol level can be measured. A comparison of the kinetic parameters of the rat liver tyrosine aminotransferase and rat brain non-specific aspartate aminotransferase towards p tyrosine has been made. PMID- 2875079 TI - Nerve growth factor action is mediated by cyclic AMP- and Ca+2/phospholipid dependent protein kinases. AB - Nerve growth factor (NGF) mediates the phosphorylation of tyrosine hydroxylase in PC12 cells on two distinct peptide fragments, separable by two-dimensional tryptic phosphopeptide mapping (phosphopeptides T1 and T3). Phorbol diester derivatives capable of activating Ca+2/phospholipid-dependent protein kinase (C kinase) cause a specific phosphorylation of peptide T3 in a dose-dependent, saturable manner. Derivatives of the endogenous C-kinase activator diacylglycerol, also cause the phosphorylation of tyrosine hydroxylase on peptide T3. The C-kinase inhibitors chlorpromazine and trifluoperazine inhibit the phorbol diester stimulated phosphorylation of site T3 in a dose-dependent manner. These agents inhibit the phosphorylation of T3 in response to NGF, but have no effect on NGF's ability to cause T1 phosphorylation. In a PC12 mutant deficient in cAMP-dependent protein kinase activity, NGF mediates the phosphorylation of tyrosine hydroxylase on peptide T3 but not on T1. We conclude that NGF mediates the activation of both the cAMP-dependent protein kinase and the C-kinase to phosphorylate substrate proteins. These kinases can act independently to phosphorylate tyrosine hydroxylase, each at a different site, and each of which results in the enzyme activation. A molecular framework is thus provided for events underlying NGF action. PMID- 2875081 TI - High-performance liquid chromatographic measurement of prazosin and terazosin in biological fluids. PMID- 2875082 TI - Enzymatic adaptation to physical training under beta-blockade in the rat. Evidence of a beta 2-adrenergic mechanism in skeletal muscle. AB - Nonselective and beta 1-selective adrenergic antagonists were tested for their effects on enzymatic adaptation to exercise training in rats as follows: trained + placebo (TC); trained + propranolol (TP); trained + atenolol (TA); and corresponding sedentary groups, SC and SP. Trained rats ran 1 h/d at 26.8 m/min, 15% grade, 5 d/wk, 10 wk. Both beta-antagonists were given at doses that decreased exercise heart rates by 25%. Training increased skeletal muscle citrate synthase, cytochrome c oxidase (Cyt-Ox), carnitine palmitoyltransferase (CPT), beta-hydroxyacyl coenzyme A dehydrogenase, mitochondrial malate dehydrogenase (MDH), and alanine aminotransferase (ALT) activities significantly in the TC group, but not in TP. These enzyme activities, except Cyt-Ox and CPT, were also significantly increased in TA. Hepatic phosphoenolpyruvate carboxykinase activity did not alter with training or beta-blockade. Fructose 1,6-bisphosphatase activity was lower in TC than in SC, but unchanged in TP or TA. Hepatic mitochondrial MDH and ALT activities increased with training only in TC. It is concluded that beta 2-adrenergic mechanisms play an essential role in the training-induced enzymatic adaptation in skeletal muscle. PMID- 2875084 TI - Trends in peptic ulcer related disease--influence of H2 antagonists. PMID- 2875083 TI - Role of insulin and glucagon in the response of glucose and alanine kinetics in burn-injured patients. AB - We investigated the roles of insulin and glucagon as mediators of changes in glucose and alanine kinetics during the hypermetabolic response to injury in 10 burn patients by infusing somatostatin with and without insulin replacement. Glucose and alanine kinetics were measured by primed-constant infusions of 6,6-d2 glucose and [3-13C]alanine. The basal rate of glucose production and alanine flux were significantly elevated in all patients. Lowering both hormones simultaneously caused an insignificant reduction in glucose production, but plasma glucose rose significantly (P less than 0.01), because of reduced clearance. Alanine flux and total plasma amino nitrogen increased significantly (P less than 0.05) above basal. Selectively lowering glucagon concentration decreased glucose production (P less than 0.05), and exogenous glucose was infused to maintain euglycemia. Alanine flux and total plasma amino nitrogen remained unchanged. In severely burned patients hyperglucagonemia stimulates increased glucose production, basal insulin suppression glucose production, stimulates basal glucose clearance, and is important for regulation of plasma amino acid concentrations, and the selective lowering of glucagon while maintaining basal insulin constant normalized glucose kinetics. PMID- 2875085 TI - Comparative cytochemical study of dipeptidyl aminopeptidase (DAP) II and IV in normal and malignant haemic cells. AB - Modified cytochemical methods were used to show dipeptidyl aminopeptidases (DAP) II and IV in peripheral blood buffy coat preparations and bone marrow smears. In 23 normal buffy coats both enzymes were confined to lymphocytes. DAP II was found in T and B lymphocytes (about 80%) while DAP IV was restricted to T lymphocytes only (around 46%). In 11 normal bone marrows DAP II was found in 53% of the lymphocytes, as well as in plasma cells, macrophages, and occasional myeloblasts. DAP IV was found only in lymphocytes (around 32%). DAP II activity, but not DAP IV activity, was present in all of the mast cells in a case of systemic mastocytosis. Whereas DAP II was found, to a variable extent, in leukaemic myeloblasts, monoblasts, proerythroblasts, and in megakaryoblasts in 52 cases of acute myeloid leukaemia, DAP IV was not shown. Variable positivity to DAP II and DAP IV was found in the lymphoblasts in seven cases of acute lymphoblastic leukaemia, in 14 cases of B chronic lymphocytic leukaemia, and in three cases of non-Hodgkin's lymphoma. DAP II activity was variable compared with DAP IV activity, which was constantly reduced. Virtually all of the myeloma cells (96%) all of the myeloma cells (96%) in five cases of multiple myeloma and two cases of plasma cell leukaemia were DAP II positive and DAP IV negative. In 10 cases of hairy cell leukaemia most hairy cells were positive to DAP II (74%) with no demonstrable DAP IV activity. In a single case of Sezary's syndrome around 90% of the helper T cells were positive to DAP II with no DAP IV activity. PMID- 2875087 TI - A case of abuse of syrup of ipecac resulting in death. PMID- 2875086 TI - LHRH and catecholamine neuronal systems in the olfactory bulb of the mouse. AB - The luteinizing-hormone-releasing hormone (LHRH) components of the mouse olfactory system were studied by using the indirect immunohistofluorescence technique. LHRH-positive cell bodies were found in both the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB); two distinct cell groups were found -one located adjacent to the AOB in the dorsal part of the MOB and a second in the superficial ventromedial aspect of the MOB. LHRH-positive fibers were found predominantly in the posterior half of the main olfactory bulb innervating the olfactory nerve layer, the glomerular layer, the external plexiform layer, and the mitral cell layer, and small numbers innervated the AOB. The greatest density of LHRH-immunoreactive fibers was seen adjacent to the AOB where one group of LHRH-positive cells was noted. Sections adjacent to those stained with LHRH antibody were analysed for tyrosine hydroxylase (TH) and dopamine beta hydroxylase (DBH). The TH staining was intense for both cells and fibers in the glomerular layer of the MOB. In the AOB lower numbers of cell bodies and fibers were seen in the glomerular layer. The internal granular layer and internal plexiform layers were both stained, the internal granular layer showing more intensely fluorescent fibers with a higher density. Since no overlapping DBH positive fibers were found here, these TH-positive nerve endings may be dopaminergic. DBH staining was confined to sparse networks of weakly fluorescent fibers with the highest numbers in the internal plexiform layer of the AOB and fewer fibers in the external plexiform, rostral, and granular layers of the MOB. Elution-restaining experiments revealed that the LHRH-positive and TH-positive elements represent different cell populations. PMID- 2875088 TI - Electrocardiographic and ventriculographic recovery patterns in Q wave myocardial infarction. AB - To further define the capacity for recovery after acute phase electrical and mechanical injury in patients with Q wave myocardial infarction who were treated with standard measures, 120 lead body surface potential maps and radionuclide angiograms were recorded at day 5 before discharge and month 6 after infarction in 23 patients with a first infarction (12 anterior and 11 inferior by standard 12 lead electrocardiographic criteria). In addition to assessment of spatial changes in electrocardiographic and wall motion patterns, five quantitative variables were evaluated: minimal Q zone integral, sigma Q wave integral, maximal ST integral, left ventricular ejection fraction and left ventricular wall motion abnormality score. From day 5 to month 6 after infarction, the only change in the inferior infarction group was a gain in sigma Q wave (-91 +/- 40 mu V X s X 10(2) to -68 +/- 24 mu V X s X 10(2); p less than 0.05). In contrast, all variables improved over the same time period in the anterior infarction group: Q zone minimum, -34 +/- 20 to -24 +/- 13 mu V X s (p less than 0.05); sigma Q wave, -160 +/- 122 X 10(2) to -120 +/- 90 mu V X s X 10(2) (p less than 0.05); ST maximum, 44 +/- 19 to 18 +/- 9 mu V X s (p less than 0.01); ejection fraction, 54 +/- 7 to 63 +/- 17% (p less than 0.05); and wall motion score, 6 +/- 3 to 3 +/- 3 (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875089 TI - Vision therapy economics. PMID- 2875090 TI - Hyperpolarizing responses of single mammalian sympathetic neurones to acetylcholine and to dopamine. AB - Acetylcholine (ACh) applied iontophoretically can elicit not only nicotinic fast (f-) and/or muscarinic slow (s-) depolarizations (DP) but also hyperpolarizing responses (HP), all in the same cell. HPs were either 'initial' (sharp onset at the end of ACh delivery) or 'secondary' (variable later onsets). Pretreatment with bretylium eliminated secondary, but not initial, responses to ACh. Pretreatment with both BCh and bretylium eliminated essentially all HP responses to ACh, with good DP responses remaining. Test responses to the more purely muscarinic agent BCh exhibited only a smooth, large s-DP with no secondary HP components, even in ganglia not pretreated with bretylium. The foregoing evidence is explainable by our previous proposals that ACh can elicit two types of HPs, one mediated by muscarinic receptors (putatively located on DA interneurones) and another by non-muscarinic receptors (putatively releasing norepinephrine at dendro-dendritic junctions). Dopamine (DA) applied iontophoretically could also elicit HP responses from the same cells. Iontophoretic DA could elicit an HP at any depth (up to 290 micron tested) in the ganglion. However, bulk application of DA (in the extra-ganglionic medium) was only effective on neurones impaled in the outer 30 micron. This may help explain the variable findings with applied DA. PMID- 2875091 TI - An animated graphics program depicting the steps in lipid peroxidation. PMID- 2875092 TI - Hyperthyroidism in Europe: clinical and laboratory data of a prospective multicentric survey. PMID- 2875093 TI - Do beta-blockers cause mesenteric ischemia? PMID- 2875094 TI - A simple modified method for mounting mosquito larvae. PMID- 2875095 TI - Urinary excretion of enzymes in cirrhotics with renal failure. AB - We studied the significance of urinary enzyme measurements in diagnosing proximal tubular damage in cirrhosis of the liver. Urinary excretion (u-enzyme) and fractional urinary excretion (FEenzyme) of gamma-glutamyltranspeptidase (GGT), leucine aminopeptidase (LAP), alkaline phosphatase (AP) and beta-glucuronidase (B GLU) were quantified in 14 control subjects (group I), 12 cirrhotics with functional renal failure (group II), 13 cirrhotics with renal tubular damage (group III) and 7 non-liver patients with renal tubular damage (group IV). Urinary enzyme excretion and fractional enzyme excretion were significantly higher in the cirrhotics of group III than in the controls or group II. In group III, these tests usually reached values within the range of group IV. The sensitivity of urinary enzyme excretion was 0.92 and specificity ranged from 0.75 (u-LAP) to 1 (u-GGT; u-B-GLU). The sensitivity of fractional enzyme excretion was between 0.61 (FEB-GLU) and 0.84 (FEGGT; FELAP), while specificity was from 0.91 (FELAP; FEAP) to 1 (FEGGT; FEB-GLU). The results indicate that measurement of urinary enzymes may be very useful in diagnosing renal tubular damage in cirrhotic patients with impaired renal function. PMID- 2875096 TI - Candida and hands. PMID- 2875097 TI - Phage typing of Staphylococcus aureus from cases of bacteraemia. PMID- 2875099 TI - A mathematical model for assessing risk of postoperative wound infection. AB - A mathematical model for predicting the risk of acquisition of postoperative wound infection in individuals or groups of patients is described. It is based on data from prevalence surveys of 41 hospitals and includes 1980 wounds. The factors included in the model, i.e., age, sex, length of pre-operative stay, type of operation, wound drainage, number of occupied beds in ward, and special factors, e.g., diabetes, steroid therapy, were obtained by stepwise regression analysis of the original data. Most of the ward facilities and practices were excluded as non-significant. The model has been modified for use with incidence studies and its accuracy confirmed in a further 1331 patients by comparing predicted and recorded infection rates. PMID- 2875098 TI - Osteomyelitis with methicillin-resistant Staphylococcus aureus. AB - We describe 10 patients with hospital-acquired osteomyelitis due to methicillin resistant Staphylococcus aureus. The patients were posttraumatic and eight had a foreign body in situ at the site of infection. Vancomycin therapy in association with radical debridement was followed by clinical and radiological cure in eight patients at 2-3.5 years follow-up, in two of whom a foreign body was left in situ. Only minor adverse effects of vancomycin therapy (one rash, two thrombophlebitis) were seen. PMID- 2875100 TI - The effects of sub-lethal concentrations of chlorhexidine on bacterial pathogenicity. AB - Suspensions of Escherichia coli and Klebsiella aerogenes were exposed to low levels of chlorhexidine, which had little effect on their in vitro viability. A substantial reduction in their in vivo infectivity measured by intraperitoneal inoculation of mice was found. This selective reduction in bacterial infectivity by chlorhexidine should be taken into account when conventional in vitro tests are used to assess the clinical effectiveness of chlorhexidine-containing antiseptics. PMID- 2875101 TI - Susceptibility of porin- and lipopolysaccharide-deficient strains of Escherichia coli to some antiseptics and disinfectants. AB - The sensitivities of some outer membrane protein (Omp) and/or lipopolysaccharide (LPS)-defective mutants of Escherichia coli to chlorhexidine and some quaternary ammonium compounds (QACs) were examined. Wild-type strains, with no defect in Omp or LPS were the most resistant to QACs, whereas LPS-deficient strains were the most sensitive. As expected, QAC resistance could not be related to the presence or absence of any specific porin(s). Chlorhexidine was highly active against all strains, inhibitory concentrations lying within the narrow range of 1 and 2 mg l 1. PMID- 2875102 TI - Handwashing and hand disinfection. PMID- 2875103 TI - The use of cefotaxime for treating suspected neonatal sepsis: 2 years' experience. AB - In 1982, the antibiotic treatment policy for suspected sepsis in neonates admitted to the Southampton special care baby unit was changed from intravenous gentamicin plus penicillin to intravenous cefotaxime with or without penicillin. Analysis of blood culture results during the first 2 years following the change indicates that a higher proportion of blood culture isolates showed sensitivity to cefotaxime compared with gentamicin. Only one baby died with proven bacterial sepsis and this was not thought to be due to treatment failure. Our data suggest that, on our unit, cefotaxime is a suitable alternative to the aminoglycosides for the management of suspected sepsis in the newborn. PMID- 2875104 TI - Biotyping and phage typing of coagulase-negative staphylococci from blood cultures of neonates. AB - One hundred coagulase-negative staphylococci isolated from blood cultures of neonates have been biotyped and phage typed. These results have been compared with previous reports. The susceptibility of the strains to antimicrobial drugs has also been examined and a rise in resistance rates towards the end of the study was documented. The possible causes of this finding are discussed. PMID- 2875105 TI - National prevalence survey of hospital-acquired infections in Italy, 1983. AB - In 1983 a national prevalence survey was conducted in Italy to discover the general distribution of infection among patients in public hospitals. Thirty-four thousand, five hundred and seventy-seven acute patients were surveyed in 130 hospitals spread throughout the country: 6668 patients (19.3%) had an active infection at the time of the survey; the infection was hospital-acquired in 2361 (6.8%) and community-acquired in 4307 (12.5%). The urinary tract was the site most frequently involved in hospital infection (30.2% of patients with hospital acquired infection). The respiratory tract was the site most often involved in community infections (35.7% for the lower tract and 9.1% for the upper). Hospital acquired infections were more frequent in intensive care units (12.4%) and in geriatric (11.6%), orthopaedic (8.2%) and surgical wards (7.6%). The prevalence of urinary tract infection was 10.4% among the 9.4% of patients who were catheterized compared with a prevalence of 2.6% in the uncatheterized. Thirty five point five per cent of patients were receiving an antimicrobial on the day of the survey. PMID- 2875106 TI - A comparison of strains of Serratia marcescens isolated from neonates with strains isolated from sporadic and epidemic infections in adults. AB - As a result of the increased number of outbreaks of Serratia marcescens in special care baby units in the UK, a study was undertaken to compare strains isolated from outbreaks of neonatal infection with strains isolated from outbreaks of infections in adults and with isolates from sporadic infections. None of the biochemical, serological, bacteriological markers examined could distinguish the three groups of strains. When considered as groups there was no difference in the ability of the strains to survive desiccation on hands. Strains from neonatal and sporadic infections were more sensitive to antibiotics than adult epidemic strains. The feature common to all of the neonatal strains tested was the ability to agglutinate one or more species of erythrocytes in the presence of mannose. Only one strain in each of the other two groups possessed mannose resistant haemagglutinins. PMID- 2875107 TI - Transfer of oropharyngeal bacteria into the trachea during endotracheal intubation. AB - Thirty-seven patients undergoing surgical operations were studied to detect transfer of oropharyngeal organisms into the trachea during endotracheal intubation. Nine of 27 patients with potentially pathogenic bacteria in the pharynx immediately before intubation were found to have these organisms, mainly Haemophilus influenzae, in the trachea at the end of operation. There was a trend for systemic antibiotic prophylaxis to reduce the persistence of bacteria in the trachea. PMID- 2875108 TI - A variable region gene subfamily encoding T cell receptor beta-chains is selectively conserved among mammals. AB - Studies of murine T cell receptor genes indicate that the VT beta repertoire, in contrast to the large VT alpha, VH, and VK repertoires, is limited to approximately 21 genes. Large differences between the various VT beta sequences allow classification into distinct subfamilies consisting of one or few members. The VT beta sequence of a gene, RTB92, expressed in a rabbit T cell line is most closely related to a VT beta gene expressed in the human cell line Molt-4. Genomic blots with RTB92 VT beta region used as probe indicated conservation of related VT beta gene subfamilies in man and pig, but no related sequences were seen in rat, mouse, or hamster. The relationship among these VT beta genes mirrors similarities and differences in MHC genes of the compared species and suggests coordinate evolution of these functionally related gene families. The constant region of RTB92 was shown to be rabbit CT beta 2 by reference to genomic clones. Comparisons with constant region sequences of human and murine CT beta 1 and CT beta 2 chains reveal no similarities in amino acid or nucleic acid sequence in the coding region characteristic of the respective isotypes. Intraspecies homologies between CT beta 1 and CT beta 2 sequences were much greater than those between CT beta 1 or CT beta 2 from other species. By contrast, comparisons of JT beta and 3' untranslated region sequences showed significant interspecies conservation of sequences in the beta 1 and in the beta 2 regions. PMID- 2875109 TI - Anti-Thy-1 plus complement-treated, cultured bone marrow cells resemble fetal thymocytes in killer cell function and marker expression. AB - Anti-Thy-1.2 plus complement treated bone marrow cells were tested after short term culture for their ability to lyse allogeneic target cells. Significant lytic activity was generated after 9 days, and required both CAS and splenic or PEC feeders as culture supplements. Allogeneic as well as syngeneic-specific cytotoxic cells were generated polyclonally under such conditions, and could be separated by using limiting dilution protocols. When 65 clones were tested for lytic activity toward three targets bearing H-2k, H-2d, and H-2b haplotypes, respectively, only two clones lysed all three targets; 53 clones showed specificity toward one target only. Targets low in class I H-2 expression were lysed only minimally compared with high H-2 expressors. Allogeneic-kill by C57BL/6 bone marrow cells grown on AKR feeder cells was destroyed by treating effectors with anti-Thy-1.2, but not anti-Thy-1.1, antibody plus complement, suggesting 1) a de novo generation of surface Thy-1 during culture and 2) that effectors were derived from bone marrow, but not feeder, populations. Partial inhibition of kill occurred by treatment of effectors with anti-asialo-GM1 (approximately 80%), anti-Lyt-2 (approximately 60%), or anti-Ly-5.1 (approximately 30%) antibodies plus complement; treatment of effectors with anti L3T4 or anti-NK-1.1 antibodies plus complement had no effect. When precursor populations were treated with either anti-Thy-1.2 alone or a combination of anti Thy-1.2 and anti-Lyt-2 antibodies plus complement, killers were easily demonstrated. However, the addition of an anti-asialo-GM1 antibody plus complement treatment before culture abolished function. The characteristics of these effectors showed a resemblance to those described previously for day 14 to 17 fetal thymocytes, designated pCTL. PMID- 2875110 TI - Differential sensitivity of T suppressor cell expression to inhibition by histamine type 2 receptor antagonists. AB - The ability of the histamine type 2 (H2) receptor antagonists cimetidine and oxmetidine to inhibit the immune suppression mediated by different types of murine T suppressor cells has been evaluated. Both compounds at doses as low as 1 mg/kg administered as a per os (p.o.) twice a day (b.i.d.) regimen abrogated the expression of dinitrobenzene sulfonic acid-induced, Lyt-2+, T suppressor cells and stimulated contact sensitivity to dinitrofluorobenzene in adoptive transfer experiments. Comparable inhibition of Lyt-1+, T suppressor cell activity induced by UV irradiation required higher doses of cimetidine and oxmetidine (200 and 25 mg/kg; p.o., b.i.d., respectively). In contrast, the T suppressor cell-mediated unresponsiveness induced by inoculation with a high dose of sheep red blood cells was refractory to treatment in vivo with either cimetidine or oxmetidine regardless of the dose. These results indicate that T suppressor cell populations differ markedly in their susceptibility to modulation by H2 antagonists. The histamine type 1 (H1) receptor antagonist diphenhydramine, had no effect on suppressor cell activity in any of these systems, indicating that modulation of suppressor cell activity is mediated through an H2 receptor interaction. PMID- 2875111 TI - Association of Bordetella pertussis-induced hypersensitivity to serotonin with the H-2 gene complex. AB - Susceptibility to Bordetella pertussis-induced sensitivity to serotonin was found to be associated with the H-2 gene complex in mice. H-2 congenic and independent strains which possess the H-2b and H-2s haplotypes were susceptible to serotonin sensitization by pertussigen (P-HSF) while mice with the H-2k and H-2d haplotypes were resistant. The gene or genes which control susceptibility were found to map to the H-2SbDb end of the H-2 complex; susceptibility appears to be inherited as a co-dominant trait. These findings indicate that HLA typing may be of value in predicting or interpreting possible adverse reactions to pertussis vaccine or infection in humans. PMID- 2875112 TI - Field evaluation of Bacillus sphaericus strain 1593 as a mosquito biocide. PMID- 2875113 TI - Changes in expression of Ia, Thy-1, and Ly-5 antigens in epidermal cells during delayed contact sensitivity reactions in mice: flow cytometric analysis. AB - Ia antigen-bearing (Ia+) Langerhans cells have attained an important position as immunocompetent cells in the epidermis. Recently there have been successive reports on other new possible candidates for immunocompetent cells in the epidermis, i.e., Ia+ keratinocytes and dendritic Thy-1 antigen-bearing (Thy-1+) epidermal cells which also express Ly-5 antigen and asialo-GM1. Based on our previous findings that in allergic contact sensitivity reactions, keratinocytes express Ia antigen 3-9 days postchallenge, in this report, we have attempted to define more clearly the dynamic changes of Ia+ keratinocytes and dendritic Thy-1+ epidermal cells by enumeration of the precise percentages of Ia+, Thy-1+, and Ly 5 antigen-bearing (Ly-5+) cells in epidermal cells at various times of the challenge phase in allergic contact sensitivity reactions by use of a fluorescence-activated cell sorter. By 24 h postchallenge, the percentages of Ia+, Thy-1+, and Ly-5+ cells showed hardly any change. There were approximately 2% Ia+ cells, 50% Thy-1+ cells which consist of 2 populations (i.e., 45% weakly Thy-1 antigen-positive cells and 4% strongly Thy-1 antigen-positive cells), and 3.5% Ly-5+ cells. From 48 h postchallenge, however, the percentage of Ia+ cells and that of Thy-1+ cells began to increase and reached a plateau, with approximately 20% Ia+ cells and 70% Thy-1+ cells, respectively, at 120 h postchallenge. The change of the percentages of Ly-5+ cells appears to correspond to that of strongly Thy-1 antigen-positive cells. Only at 48 h postchallenge, Ly 5+ cells and strongly Thy-1 antigen-positive cells showed a small increase in number, comprising approximately 10% of the epidermal cells. These data suggest that among Thy-1+ epidermal cells, strongly Thy-1 antigen-positive cells correspond to dendritic Thy-1+ epidermal cells, and in contact sensitivity reactions in mice, dendritic Thy-1+ epidermal cells show only a minor dynamic change in contrast to Ia+ cells, in which more than 15% of keratinocytes express Ia antigen from 48 h postchallenge. PMID- 2875114 TI - Ontogeny of Ia-positive and Thy-1-positive leukocytes of murine epidermis. AB - Murine epidermis harbors 2 populations of dendritic leukocytes: Langerhans cells (LC) and Thy-1-positive dendritic epidermal cells (Thy-1 +DEC). In the adult mouse these cell types are morphologically distinct and display highly characteristic phenotypes. LC bear Ia-antigens and a group of markers typical for mononuclear phagocytes: Fc- and C3bi-receptors, macrophage-specific antigen F4/80, and membrane ATPase. Thy-1 +DEC, in contrast, lack these markers but express high levels of Thy-1 and asialo-GM1 (asGM1) antigen. Since LC and Thy-1 +DEC share a common origin from the bone marrow we expected to gain insight into their relationship by studying their ontogenetic development. Epidermal sheets from fetal and newborn C3H/He and C57B1/6 mice obtained at defined ages from day 17 of gestation up to day 30 of postnatal life were monitored for the emergence of the above-mentioned markers for LC and Thy-1 +DEC. In double-labeling experiments LC markers were first detected by visualizing the monoclonal antibodies by a sensitive triple-layer rhodamine-immunofluorescence technique; in a second step, after appropriate blocking procedures, Thy-1 and asGM1 antigens were demonstrated by direct and indirect immunofluorescence. We found that in fetal epidermis, only few cells expressed either Thy-1 or Ia (4 and 1 cells/mm2, respectively, on day 18 of gestation). The bulk of Thy-1 +DEC and Ia +EC appeared only after birth. Adult proportions of Thy-1 +DEC and Ia +EC were reached at around 1 month of postnatal life. In contrast, all the other LC markers were expressed on a substantial number of fetal dendritic cells (280 cells/mm2 on day 18 of gestation), indicating the presence of phenotypically immature Ia-negative LC in fetal epidermis. By day 4 of postnatal life all F4/80 +EC and ATPase +EC (i.e., LC) had acquired Ia-antigens. Surprisingly, LC also bore asGM1 antigens, which in the adult epidermis are strictly confined to Thy-1 +DEC, up to day 5 of postnatal life. Thus, LC in fetal and early newborn epidermis are not yet fully differentiated. As they differentiate, they acquire Ia antigens and lose asGM1 antigens. In contrast, a phenotypically immature Thy-1 +DEC population could not be traced with the markers used. Thy-1 +DEC appear to be characterized by a stable phenotype (Thy-1+/asGM1+) throughout their lifetime. PMID- 2875115 TI - Heterogeneity of epidermal Thy-1-positive cells defined by lectin-binding sites. AB - A new cell type that expresses Thy-1 antigen (dendritic epidermal Thy-1-positive cells, d-Thy-1+ EC) was discovered in the murine epidermis in 1983. It is not clear, however, whether all d-Thy-1+EC represent a unitary population. We investigated the cell surface glycoconjugate pattern of d-Thy-1+EC using 6 lectins: concanavalin A (Con-A), Dolichos biflorus agglutinin (DBA), Ricinus communis agglutinin 1 (RCA-1), wheat germ agglutinin (WGA), Ulex europaeus agglutinin (UEA-1), and peanut agglutinin (PNA). These lectins could be divided into 3 groups: lectins binding to most d-Thy-1+EC (Con-A and RCA-1); lectins virtually unreactive with d-Thy-1+EC (DBA and UEA-1); and lectins binding to subpopulation of d-Thy-1+EC (WGA and PNA). For lectins of group 1 and group 2, no difference was observed from strain to strain of mice (C3H/He, BALB/c, and C57B1/6), or from site to site of the body (back, ear, and tail). However, striking difference of percentage of lectin-binding d-Thy-1+EC was observed in group 3 lectins in the tail region compared with the back or the ear, although no strain difference was noted: back or ear, 83.6-95.5% with PNA, 13.6-29.6% with WGA in C3H; tail, 4.0-19.4% with PNA, 30.0-59.1% with WGA in C3H. These results indicate that d-Thy-1+EC are a heterogeneous population and that their distribution is different from site to site in the body. PMID- 2875116 TI - Dopa oxidase activity in human hair bulbs measured by high-performance liquid chromatography. AB - A method for measuring the dopa oxidase (DO) activity of human hair bulb tyrosinase has been developed and the results of this method have been compared with the tyrosine hydroxylase (TH) activity of hair bulb tyrosinase for brown-, black-, blond-, and red-haired subjects. The method takes advantage of the rapid trapping of dopaquinone by cysteine with the subsequent formation of cysteinyldopas which can be measured by high-performance liquid chromatography. 5 S-Cysteinyldopa (5SCD) and 2-S-cysteinyldopa (2SCD) were detected in the reaction products. Formation of 5SCD correlated with the TH activity over the full range of hair colors and enzyme activity, while 2SCD appeared to be formed nonenzymatically. The absolute amount of 2SCD was constant for each individual but did not correlate with hair color or TH activity. The formation of 5SCD was linear for 60 min while most of the 2SCD was formed within seconds and did not change with time. White hair bulbs which demonstrated no TH activity formed 2SCD, but not 5SCD. We conclude that tyrosinase activity can be quantitated in human hair bulbs by this method, and that TH and DO are coordinate functions of tyrosinase over a broad range of hair color and enzyme activity. PMID- 2875117 TI - The fetal liver as an alternative stem cell source for hemolymphopoietic reconstitution. AB - In mammalian ontogeny, the liver constitutes the primary hematopoietic organ for some time. Fetal liver cells (FLC) are rich in hematopoietic stem cells with a high proliferative potential but contain few post-thymic T cells. In animal studies, FLC restored hematopoiesis without severe graft-versus-host disease. However, genetic disparity between donor and host frequently limited durable engraftment and prevented or protracted complete immune reconstitution in most fully allogeneic recipients. Some children with severe combined immunodeficiency have been cured by FLC infusion, whereas favorable effects in aplastic anemia, acute leukemia, and inborn errors of metabolism have been limited and badly understood. Fetal liver transplantation in animals may serve as a model for the analysis and management of complications associated with the transfer of purified hematopoietic stem cell grafts and aid in the development of future therapeutic strategies requiring rapidly proliferating stem cell populations. PMID- 2875118 TI - Failure of bone marrow cryopreservation in chronic granulocytic leukemia: relation to excessive granulo-macrophagic progenitor pool. AB - Autologous bone marrow transplantation (ABMT) in chronic granulocytic leukemia (CGL) aims at reversing the acute or acceleration phases by injection of stem cells collected during the chronic phase. This study was designed to explain an unusual rate of delayed engraftment (50%) in our experience of ABMT in CGL patients. We investigated all the factors possibly responsible for abnormal perpetuation of aplasia following infusion of cryopreserved marrow stem cells. The study of CFU-gm recovery in 41 bags of frozen marrow from 25 patients revealed an overall deficiency with a mean CFU-gm recovery of 55 +/- 38% in CGL patients versus 73 +/- 15% in the control group (p less than 0.001). Our data also showed an inverse linear relation (r = -0.40, p less than 0.05) between CFU gm concentration and recovery after freezing. A good CFU-gm recovery (greater than or equal to = 50%) was observed in 70% of cases when the concentration was less than 3700 CFU-gm/ml as compared to 30% of cases when the concentration was over 3700 CFU-gm/ml (p less than 0.001). The lack of improvement by diluting rich CFU-gm marrows to reduce CFU-gm concentration/ml, as well as the absence of relationship between CFU-gm recovery after freezing and nucleated cells concentration, suggest a particular fragility of CGL stem cells to freezing, probably related to their excessive amplification. At the present time, we strongly recommend that the highest possible dose of progenitor cells be cryopreserved, preferably at a low concentration, in patients with CGL, and particular attention devoted to the freezing procedure in each individual patient, with numerous appropriate efficiency tests. PMID- 2875119 TI - Multiple endocrine neoplasia, type III. AB - Multiple oral plexiform neuromas in a 14-year-old white girl prompting screening of the patient with respect to the multiple endocrine neoplasia (MEN) type-III syndrome, verified the existence of a thyroid medullary carcinoma and the diagnosis MEN-type III. Total thyroidectomy was performed, but extensive tumour infiltration prevented radical tumour excision. The condition being relatively infrequent, the important life-saving role of dental practitioners and oral surgeons in its recognition and early diagnosis is emphasized. PMID- 2875120 TI - [Successful treatment of polyarteritis nodosa by plasmapheresis]. PMID- 2875121 TI - Establishment of a continuous somatostatin-producing line of medullary thyroid carcinoma cells from BALB/c mice. AB - A continuous line of somatostatin-producing medullary thyroid carcinoma cells was established from a transplantable tumour in BALB/c mice. Virtually all of the somatostatin immunoreactivity co-chromatographed with somatostatin 14. The tumour cells replicated in spinner cultures with a doubling time of approximately 4 days, and the concentration of somatostatin released into the culture medium increased in proportion to the number of cells. Two- to threefold increases in amounts of stored and released somatostatin were observed after treatment of the cells with bromodeoxyuridine. This cell line might be valuable for studies of somatostatin regulation in normal and neoplastic C-cells, and for other studies of C-cell biology which require a mouse model. PMID- 2875122 TI - Diagnosis of coronary artery disease by exercise radionuclide angiocardiography. PMID- 2875123 TI - Pathogenesis of scrapie: study of the temporal development of clinical symptoms, of infectivity titres and scrapie-associated fibrils in brains of hamsters infected intraperitoneally. AB - After an intraperitoneal infection of hamsters with scrapie agent, early low and constant titres of about 100 LD50/brain between days 10 to 50 were followed by a dramatic increase to maximum levels of 3 X 10(9) LD50/brain within about 15 days. The plateau of maximum infectivity remained unchanged from day 70 to the time of the first and final signs of disease at 95 and 123 days post-infection, respectively. Scrapie-associated fibrils (SAF) as measured by immunoblotting of SAF protein could not be detected before 79 days post-infection even when a total brain was used for analysis. Subsequently, the concentration of SAF increased gradually by about 100,000-fold until the time of clinical disease. The kinetics suggest a virus-induced amyloidosis of the brain as the cause of disease. PMID- 2875125 TI - Effects of antidepressants and other psychotropic drugs on melatonin release and pineal gland function. AB - Antidepressants and some other psychotropic drugs affect the synthesis and release of melatonin through several mechanisms. Monoamine oxidase (MAO) inhibiting antidepressants increase pineal concentrations of the melatonin precursors, serotonin (5-HT) and N-acetyl serotonin (NAS), in rodents, and also increase pineal N-acetyl transferase activity as well as both daytime and nighttime plasma melatonin concentrations; they also elevate melatonin, 5-HT and NAS in the cerebrospinal fluid of non-human primates. In humans treated with the MAO-A selective inhibitor, clorgyline, or the nonselective inhibitor, tranylcypromine, increased plasma melatonin also occurs; in contrast, the MAO-B selective inhibitor, 1-deprenyl, does not affect plasma melatonin. Chronically administered tricyclic antidepressants with prominent effects on monoamine uptake and on beta-adrenoceptors reduce pineal and plasma melatonin in rodents; however, in two studies in depressed patients, either no change or a significant elevation in nocturnal plasma melatonin followed 3 to 4 weeks treatment with desipramine. As depressed patients in these and several other recent studies had lower pretreatment nighttime melatonin peaks than controls, these findings may be relevant to the presynaptic and receptor adaptational consequences of chronic antidepressant drug treatment. The significant effects on melatonin of other drugs which affect monoamine function and have psychotropic effects, including lithium, propranolol, amphetamine and several monoamine precursors, together with recent observations of the existence of muscarinic and benzodiazepine receptors in the pineal gland are in accord with previous suggestions that the study of pineal function and melatonin production provides a valuable model system for psychopharmacological investigations. PMID- 2875124 TI - Neural pathways and neurotransmitters affecting melatonin synthesis. AB - In addition to its sympathetic innervation, a mammalian pineal gland also receives a distinct central pinealopetal innervation. Earlier studies in rat have established that the photic signals originating in the retina pass via the retinohypothalamic tract to the suprachiasmatic nucleus, to the tuberal hypothalamus, over medial forebrain bundle, reticular formation, and upper thoracic interomediolateral cell column to the superior cervical ganglion, whose postganglionic sympathetic fibers, traveling along the tentorium cerebelli, enter the pineal gland via the conarian nerve. Recent electron microscopic analyses of the pineal gland of several mammalian species have revealed intrapineal nerve terminals different from the sympathetic ones. In addition, lesion experiments performed in the habenular nuclei or the posterior commissure support the central origin of these terminals. The intact sympathetic innervation, the functional beta-adrenergic receptors, and the appropriate level of norepinephrine are all essential prerequisites for the circadian pattern of melatonin synthesis. However, other receptors such as alpha-adrenergic, D2-dopaminergic, GABAergic, benzodiazepinergic, and glutamatergic receptors and their agonists are also able to modulate the synthesis of melatonin, and this function depicts dramatic species variation. The impact of pinealopetal projections and intrapineal neurons on the physiological and biochemical aspects of pineal functions awaits clarification. PMID- 2875126 TI - Synaptosomal transport of radiolabel from N-acetyl-aspartyl-[3H]glutamate suggests a mechanism of inactivation of an excitatory neuropeptide. AB - This study was undertaken to explore in synaptosomal preparations the disposition of N-acetyl-aspartyl-glutamate (NAAG), an endogenous acidic dipeptide neurotransmitter candidate. Radiolabel from N-acetyl-aspartyl[3H]glutamate was taken up rapidly into an osmotically sensitive compartment by rat brain synaptosomal preparations in a sodium-, temperature-, and time-dependent manner. HPLC analysis of the accumulated radiolabel indicated that the bulk of the tritium cochromatographed with glutamic acid and not with NAAG. In contrast, [14C]NAAG, labeled on the N-terminal acetate, was not taken up by the synaptosomal preparation. All effective inhibitors of synaptosomal, Na+-dependent [3H]glutamate uptake were found to exhibit similar potency in inhibiting uptake of tritium derived from [3H]NAAG. However, certain alpha-linked acidic dipeptides, structurally similar to NAAG, as well as the potent convulsant quisqualic acid inhibited synaptosomal transport of [3H]NAAG but were ineffective as inhibitors of [3H]glutamate transport. Together with a demonstration of disparities between the regional accumulation of radiolabel from [3H]NAAG and high-affinity [3H]glutamate uptake, these data suggest the presence in brain of a specific peptidase targeting carboxy-terminal glutamate-containing dipeptides that may be coupled to the Na+-dependent glutamate transporter. These findings provide a possible mechanism for NAAG inactivation subsequent to its release from nerve endings. PMID- 2875128 TI - Transport of cysteate by synaptosomes isolated from rat brain: evidence that it utilizes the same transporter as aspartate, glutamate, and cysteine sulfinate. AB - Synaptosomes isolated from rat brain accumulated cysteic acid by a high-affinity transport system (Km = 12.3 +/- 2.1 microM; Vmax = 2.5 nmol mg protein-1 min-1). This uptake was competitively inhibited by aspartate (Ki = 13.3 +/- 1.8 microM) and cysteine sulfinate (Ki = 13.3 +/- 2.3 microM). Addition of extrasynaptosomal cysteate, aspartate, or cysteine sulfinate to synaptosomes loaded with [35S]cysteate induced rapid efflux of the cysteate. This efflux occurred via stoichiometric exchange of amino acids with half-maximal rates at 5.0 +/- 1.1 microM aspartate or 8.0 +/- 1.3 microM cysteine sulfinate. Conversely, added extrasynaptosomal cysteate exchanged for endogenous aspartate and glutamate with half-maximal rates at 5.0 +/- 0.4 microM cysteate. In the steady state after maximal accumulation of cysteate, the intrasynaptosomal cysteate concentrations exceeded the extrasynaptosomal concentrations by up to 10,000-fold. The measured concentration ratios were the same, within experimental error, as those for aspartate and glutamate. Depolarization, with either high [K+] or veratridine, of the plasma membranes of synaptosomes loaded with cysteate caused parallel release of cysteate, aspartate, and glutamate. It is concluded that neurons transport cysteate, cysteine sulfinate, aspartate, and glutamate with the same transport system. This transport system catalyzes homoexchange and heteroexchange as well as net uptake and release of all these amino acids. PMID- 2875127 TI - Characterization of L-glutamate binding sites in rat spinal cord synaptic membranes: evidence for multiple chloride ion-dependent sites. AB - The effects of various ions on L-glutamate (L-Glu) binding sites (Na+-dependent, Cl(-)-dependent, and Cl(-)-independent) in synaptic plasma membranes (SPM) isolated from rat spinal cord and forebrain were examined. Cl(-)-dependent binding sites were over twofold higher in spinal cord (Bmax = 152 +/- 34 pmol/mg protein) as compared to forebrain SPM (Bmax = 64 +/- 12 pmol/mg protein). Na+ dependent binding, on the other hand, was nearly sixfold less in spinal cord (Bmax = 74 +/- 10 pmol/mg protein) compared to forebrain SPM (408 +/- 26 pmol/mg protein). Uptake of L-Glu (Na+-dependent) was also eightfold less in the P2 fraction from spinal cord relative to forebrain (Vmax of 2.89 and 22.3 pmol/mg protein/min, respectively). The effects of Na+, K+, NH4+, and Ca2+ on L-Glu binding sites were similar in both regions of the CNS. In addition, in spinal cord membranes, Br-, I-, and NO3- were equivalent to Cl- in their capacity to stimulate L-Glu binding, whereas F- and CO3- were less effective. Cl(-)-dependent L-Glu binding in spinal cord membranes consisted of two distinct sites. The predominant site (74% of the total) had characteristics similar to the Cl(-) dependent binding site in forebrain membranes [i.e., Ki values of 5.7 +/- 1.4 microM and 119 +/- 38 nM for 2-amino-4-phosphonobutyric acid (AP4) and quisqualic acid, (QUIS), respectively]. The other Cl(-)-dependent site was unaffected by AP4 but was blocked by QUIS (Ki = 14.2 +/- 4.8 microM). PMID- 2875129 TI - Effects of arachidonic acid on glutamate and gamma-aminobutyric acid uptake in primary cultures of rat cerebral cortical astrocytes and neurons. AB - The effects of arachidonic acid on glutamate and gamma-aminobutyric acid (GABA) uptake were studied in primary cultures of astrocytes and neurons prepared from rat cerebral cortex. The uptake rates of glutamate and GABA in astrocytic cultures were 10.4 nmol/mg protein/min and 0.125 nmol/mg protein/min, respectively. The uptake rates of glutamate and GABA in neuronal cultures were 3.37 nmol/mg protein/min and 1.53 nmol/mg protein/min. Arachidonic acid inhibited glutamate uptake in both astrocytes and neurons. The inhibitory effect was observed within 10 min of incubation with arachidonic acid and reached approximately 80% within 120 min in both types of culture. The arachidonic acid effect was not only time-dependent, but also dose-related. Arachidonic acid, at concentrations of 0.015 and 0.03 mumol/mg protein, significantly inhibited glutamate uptake in neurons, whereas 20 times higher concentrations were required for astrocytes. The effects of arachidonic acid were not as deleterious on GABA uptake as on glutamate uptake in both astrocytes and neurons. In astrocytes, GABA uptake was not affected by any of the doses of arachidonic acid studied (0.015 0.6 mumol/mg protein). In neuronal cultures, GABA uptake was inhibited, but not to the same degree observed with glutamate uptake. Lower doses of arachidonic acid (0.03 and 0.015 mumol/mg protein) did not affect neuronal GABA uptake. Other polyunsaturated fatty acids, such as docosahexaenoic acid, affected amino acid uptake in a manner similar to arachidonic acid in both astrocytes and neurons. However, saturated fatty acids, such as palmitic acid, exerted no such effect. The significance of the arachidonic acid-induced inhibition of neurotransmitter uptake in cultured brain cells in various pathological states is discussed. PMID- 2875130 TI - Investigation of dopamine content, synthesis, and release in the rabbit retina in vitro: II. Effects of high potassium, adenylate cyclase activators, and N-n propyl-3-(3-hydroxyphenyl) piperidine. AB - The modulation of 3,4-dihydroxyphenylethylamine (dopamine, DA) synthesis and release in rabbit retina in vitro by high K+; adenylate cyclase activators such as forskolin, 2-chloroadenosine, vasoactive intestinal polypeptide (VIP); and the putative DA autoreceptor agonist N-n-propyl-3-(3-hydroxyphenyl) piperidine (3 PPP) has been investigated. Incubation of retinas in 50 mM K+ resulted in the activation of tyrosine hydroxylase (TH). Activation did not require the presence of extracellular Ca2+. K+ 50 mM also induced a Ca2+-dependent release of DA. Forskolin 50 microM stimulated TH but 100 microM 2-chloroadenosine and 650 nM VIP did not. Individually, (+)-3-PPP, (-)-3-PPP, and (+/-)-3-PPP reduced DA synthesis and increased its release. The effects of (+/-)-3-PPP were dose-dependent and did not require the presence of extracellular Ca2+. The activation of TH induced by 50 mM K+, but not that induced by 50 microM forskolin, was abolished by 100 microM (+/-)-3-PPP. PMID- 2875131 TI - Characteristics of the beta-adrenoreceptor from neuronal and glial cells in primary cultures of rat brain. AB - The cellular characteristics of the beta-adrenoreceptor in glial and neuronal cells from the newborn rat brain were determined by (-)-[125I]iodocyanopindolol binding. In membranes from both cell types, the binding was saturable and from competition assays the potency series of (-)-isoproterenol greater than (-) epinephrine = (-)-norepinephrine greater than (+)-isoproterenol was observed. 5' Guanylyl-imidodiphosphate reduced the affinity of (-)-isoproterenol for the beta adrenoreceptor from glial cells but had no effect on agonist affinity in neuronal cells. Chronic treatment of both cell types with (-)-isoproterenol reduced the receptor content and the capacity of the agonist to increase the cellular cyclic AMP content. However, the receptor recovery after chronic agonist treatment was faster in glial cells (72 h) than neuronal cells (120 h) and was blocked by cycloheximide. Treatment of both types with the irreversible beta-blocker bromoacetylalprenololmentane (2 microM) reduced the receptor content by 78% but no receptor recovery was observed for 120 h after the initial receptor loss. The data indicated that the majority of beta-adrenoreceptors in both cell types are the beta-1 subtype, but show some differences in receptor-agonist interactions. Furthermore, these CNS cells may be useful models for regulatory studies on the beta-adrenoreceptor. PMID- 2875132 TI - The clinical phenomenon of akathisia. AB - The subjective and motor phenomena of neuroleptic-induced akathisia were studied in two different populations of psychiatric patients. Thirty nine (41%) of 95 patients attending community psychiatric centres and psychiatric day hospitals experienced a compulsion to move about, and 52 (55%) complained of restlessness of the body. Of 842 psychiatric in-patients 159 found to have marked hyperkinesis were divided into three groups; group 1 with motor restlessness, and a subjective desire to move about or marching on the spot (27 patients), group 2 with choreo athetotic movements and motor restlessness (79 patients) and an indeterminate group 3 (53), bearing more similarities to group 1 than group 2. Motor disturbances associated with akathisia were repeated leg crossing, swinging of one leg, lateral knee movements, sliding of the feet and rapid walking. PMID- 2875133 TI - The organization and solubility properties of intermediate filaments and microtubules of cortical astrocytes in culture. AB - The organization of intermediate filaments (IF) and microtubules (MT) and the solubility of intermediate filament proteins and tubulin in astrocytes which develop from cerebral hemispheres of neonatal rats in culture were examined using immunocytochemical and immunochemical approaches. Results of immunocytochemical studies demonstrated that in flat astrocytes which develop after 3 weeks of culturing in serum-supplemented medium, the IF containing vimentin and glial fibrillary acidic protein (GFAP) are concentrated around the nucleus and dispersed in an irregular fashion throughout the cytoplasm. Astrocytes which develop in serum-free hormonally-defined medium irrespective of whether they are bipolar, multipolar or flattened, have IF organized as a fibrous network of filaments distributed from the nuclear regions to the cell periphery. Under both culture conditions, vimentin and GFAP are resistant to extraction with low salt buffer containing nonionic detergent, indicating that the different cytoplasmic distribution of IF is unrelated to the solubility properties of vimentin and GFAP. Double immunolabelling experiments with polyclonal antibody to GFAP and monoclonal antibody to each alpha-tubulin or beta-tubulin reveal an extensive codistribution and parallel organization of IF and MT in all morphological types of astrocytes studied. Stabilization of MT with taxol, or depolymerization of MT with colchicine, cause dramatic changes in the distribution of IF and inhibit the extension of astrocyte processes in response to dibutyryl cyclic AMP (dBcAMP). In early stages of treatment with dBcAMP, renewal of culture medium without dBcAMP produces a rapid and permanent retraction of astrocyte processes, whereas in later stages the processes only retract partially and are then restored and maintained for several days in the absence of dBcAMP. The retraction of processes is accompanied by changes of immunocytochemical staining of IF with antibody to GFAP, which appears more intense and diffuse. However, electrophoretic and immunoblot analyses of detergent-extracted proteins from parallel cultures demonstrate that neither the amount nor the solubility of GFAP and vimentin are changed. Detergent extraction in MT stabilizing conditions shows that a substantial proportion of tubulin in astrocytes cultured in serum-containing and serum-free media is assembled into MT, most of which depolymerize on treatment with low temperature and Ca2+. Following long exposure to dBcAMP the proportion of cold/Ca2+-stable MT increases. The results suggest that the IF of astrocytes in culture are dependent on MT with respect to their cytoplasmic distribution.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2875134 TI - Fresh cell therapy followed by fatal coma. AB - A 60-year-old woman received a 3-day course of nine injections of "fresh" cells from fetal lamb ovary, placenta, brain (hypothalamus) and liver. There were no immediate complications, but a few days later she developed headache, fever and hemiparesis. She subsequently fell into a coma and died 3 weeks after her fresh cell therapy and 2 weeks after the onset of her clinical symptoms. Autopsy revealed perivenous leucoencephalopathy with a probably steroid-treatment-induced paucity of perivascular inflammation. Fresh cell therapy, clinical symptomatology and morphological findings suggest, though do not prove, that this patient's monophasic and probably immune-mediated disease is a rare fatal complication of fresh cell therapy. PMID- 2875135 TI - In vitro release and electrophysiological effects in situ of homocysteic acid, an endogenous N-methyl-(D)-aspartic acid agonist, in the mammalian striatum. AB - A potassium-induced, calcium-dependent release of endogenous homocysteic acid (HCA) from rat striatal slices was demonstrated. A precolumn derivatization high performance liquid chromatography method was developed that allowed quantitative determination of sulfur-containing amino acids at the picomole level. Intracellular recordings from cat caudate neurons during simultaneous microiontophoretic application of drugs and electrical stimulation of the corticocaudate pathway showed that (L)-HCA evoked a depolarization pattern similar to that induced by N-methyl-(D)-aspartic acid (NMDA), and both these depolarizations could be selectively inhibited by a specific NMDA antagonist, (D) 2-amino-7-phosphonoheptanoic acid [(D)-AP-7]. A selective antagonism of (L)-HCA induced depolarizations by (D)-AP-7 was confirmed in quantitative experiments with the frog hemisected spinal cord in vitro. Small quantities of iontophoretically applied (L)-HCA, but not of quisqualate, potentiated cortically evoked EPSPs in cat caudate neurons. These observations suggest that (L)-HCA might be a candidate as an NMDA-receptor-preferring endogenous transmitter in the caudate nucleus. One possible function for such transmitter systems could be the enhancement of EPSPs. PMID- 2875136 TI - Actions of pentobarbital on rat brain receptors expressed in Xenopus oocytes. AB - Functional receptor channels activated by GABA and other neurotransmitters were "transplanted" from rat brain to Xenopus oocytes by injecting the oocytes with total poly(A)+ mRNA isolated from rat or chick brain. Membrane currents elicited in the oocyte by GABA inverted polarity at about the chloride equilibrium potential (ca. -25 mV). Pentobarbital potentiated the GABA-activated currents, without appreciably changing the reversal potential or form of the current voltage relationship. At low (less than 10(-5) M) concentrations of GABA, pentobarbital (100 microM) potentiated the responses by a factor of 10 or more, but responses to high (ca. 1 mM) concentrations of GABA were almost unchanged. Half-maximal activation of the response was obtained with about 3 X 10(-5) M GABA when applied alone and with about 4 X 10(-6) M GABA when applied together with 100 microM pentobarbital. At low doses of GABA, the size of the current increased as the 1.4th power of GABA concentration, but this relationship became nearly linear in the presence of pentobarbital. The potentiation of the GABA response increased linearly with concentrations of pentobarbital up to about 300 microM, reaching a maximum of about 50-fold. At higher concentrations of pentobarbital, the response to GABA declined. Relaxations of GABA-activated currents following voltage steps became slower in the presence of pentobarbital, suggesting that the open life-time of the channels was prolonged. In addition to actions on GABA activated currents, pentobarbital itself elicited a small membrane current that inverted polarity at a potential (-10 mV) more positive than the GABA-activated current.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875137 TI - Topography of NPY-, somatostatin-, and VIP-immunoreactive, neuronal subpopulations in the guinea pig celiac-superior mesenteric ganglion and their projection to the pylorus. AB - The topography of the peptidergic neuronal subpopulations in the guinea pig celiac-superior mesenteric ganglion was studied analyzing the distribution of immunoreactivity to neuropeptide Y (NPY), somatostatin (SOM), and vasoactive intestinal polypeptide (VIP)/polypeptide HI (PHI). For comparison, the ganglion was also studied using antisera against the 2 catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). Approximately 65% of the neuronal cell bodies contained NPY-like immunoreactivity (NPY-LI), whereas 25% of the principal ganglion cells contained SOM-like immunoreactivity (SOM-LI). Though occasional cells were found to contain both NPY-LI and SOM-LI, these peptides had a complementary distribution in the ganglion, with NPY cells in the celiac poles and SOM cells in the superior mesenteric pole. The vast majority of both the NPY- and SOM-positive cells also contained TH-like immunoreactivity (TH LI), confirming their catecholaminergic, presumably noradrenergic, nature. Some noradrenergic neurons seemed to lack NPY- and SOM-LI. Small numbers of VIP/PHI containing cell bodies were found in areas where the NPY-immunoreactive neurons predominated. Many of the VIP/PHI-positive cells contained NPY-LI and occasionally also TH-LI. The immunohistochemical markers were also observed in fibers. Thus, a comparatively weak NPY-LI was seen in smooth fibers, probably representing axons and axon bundles. SOM-LI was seen in a similar type of fiber but also in more strongly fluorescent fibers with a varicose appearance. The latter fibers were observed only in the SOM-dominated part of the ganglion, often surrounding the ganglion cells. Varicose fibers with a similar distribution containing DBH-like immunoreactivity (DBH-LI) were also seen. In addition, DBH- and TH-LI were seen in smooth axonlike processes. VIP-positive fibers exhibited a very dense fiber network, almost exclusively related to the SOM cell-dominated part of the ganglion. The projection of the postganglionic sympathetic neurons was studied with special reference to the pylorus using a combination of retrograde axonal tracing and indirect immunofluorescence techniques. Seventy-two hours after injection of the fluorescent tracer Fast Blue into the pyloric sphincter, labeled neurons were found in the ganglion. By comparing the Fast Blue labeled cells with the immunoreactive cell bodies, neurons containing both dye and NPY- or SOM-LI were observed. In elution-restaining experiments, it was established that the majority of these cells were also immunoreactive to TH, indicating that they produce noradrenaline.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2875138 TI - Respiratory motoneuronal activity is altered by injections of picomoles of glutamate into cat brain stem. AB - The local neural circuitry underlying the control of breathing was studied by injecting nanoliter volumes of excitatory amino acids into discrete regions of cat brain stem. Experiments were performed on chloralose-urethane anesthetized, vagotomized, paralyzed, and artificially ventilated cats. Phrenic, intercostal, and recurrent laryngeal nerve discharges were recorded. Multibarrel pipettes were used for recording and pressure ejection of drugs or a dye for marking recording and ejection sites. Ejected volumes were directly monitored for every injection. Injections, proximal to neurons discharging with a respiratory periodicity, of as little of 200 fmol of L-glutamate in 200 pl of saline elicited marked, site specific increases or decreases in respiratory motoneuronal discharge. N-Methyl-D aspartic acid and homocysteic acid elicited similar site-specific alterations in respiratory motor output, although some details of the response could differ qualitatively. Responses to all the excitatory agents used were attenuated by concurrent injection of kynurenic acid, DL-2-amino-4-phosphonobutyric acid, or glutamic acid diethyl ester. There was no change in spontaneous phrenic nerve discharge in response to injections of equivalent or larger volumes of saline or lidocaine. These results indicate a heterogeneity in the spatial organization of the brain-stem neural circuitry underlying respiratory control, which has not been described previously. This injection technique may provide a mechanism for probing the neural circuitry underlying other behaviors. PMID- 2875139 TI - Actions of opioids on primate spinothalamic tract neurons. AB - The effects of iontophoretically applied opiates were tested on 24 spinothalamic tract cells in 12 anesthetized monkeys. The drugs used were chosen because of their agonist actions on different classes of opiate receptors (mu, morphine; kappa, dynorphin; delta, methionine enkephalinamide; sigma, N-allylnormetazocine or SKF 10047 and phencyclidine). The actions of the opiate drugs were generally inhibitory, although excitatory or mixed effects were sometimes seen, especially with morphine and dynorphin. Drug effects could change, depending on the position of the iontophoretic electrode array or on the current employed. Naloxone sometimes antagonized the action of the opiate drugs used, but naloxone did not seem to be a drug suited for iontophoretic application. A number of explanations are discussed to explain the variable actions of the opiate drugs. PMID- 2875140 TI - Tyrosine hydroxylase in the rat parabrachial region: ultrastructural localization and extrinsic sources of immunoreactivity. AB - We sought to determine the ultrastructural localization and the extrinsic sources of the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), in the lateral parabrachial region (PBR) of adult male rats. In the first portion of the study, a rabbit antiserum to TH was immunocytochemically localized in coronal sections through the lateral PBR from acrolein-fixed brains using the peroxidase antiperoxidase method. Electron-microscopic analysis revealed that perikarya and dendrites with peroxidase immunoreactivity for TH constituted only 17% of the total labeled profiles. Afferents to the TH-labeled perikarya and dendrites usually failed to exhibit immunoreactivity and were thus considered noncatecholaminergic. Somatic synapses were most commonly detected on small immunoreactive perikarya in the central lateral nucleus of the PBR. Other labeled perikarya located in the dorsal lateral or ventral lateral nuclei received few somatic synapses and were morphologically distinct in terms of their larger size, infolded nuclear membrane, and abundance of cytoplasmic organelles. Axons and axon terminals with peroxidase immunoreactivity constituted the remaining labeled profiles in the lateral PBR. These terminals primarily formed symmetric synapses with unlabeled and a few labeled dendrites. The labeled axon terminals were categorized into 2 types: Type I was small (0.3-0.6 micron), contained many small clear vesicles, and exhibited few well-defined synaptic densities. The second type was large (0.8-1.4 micron), contained both small clear and large dense core vesicles, and exhibited well-defined synaptic densities. The 2 types of terminals were morphologically similar to dopaminergic terminals. The location of catecholaminergic neurons contributing to the TH-labeled terminals was determined by combining peroxidase-antiperoxidase immunocytochemistry for TH with retrograde transport of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP). The tracer was unilaterally injected into the PBR of anesthetized adult rats. Immunocytochemical labeling for TH was seen as a brown reaction product within neurons in known catecholaminergic cell groups. A black granular reaction product formed by a cobalt-intensified and diaminobenzidine-stabilized tetramethyl benzidine reaction for WGA-HRP was evident within many TH-labeled and unlabeled neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2875141 TI - Effects of capsaicin on lipid metabolism in rats fed a high fat diet. AB - Effects of capsaicin, a pungent principle of hot red pepper, were studied in experiments using male rats fed a diet containing 30% lard. Capsaicin was supplemented at 0.014% of the diet. The level of serum triglyceride was lower when capsaicin was present in the diet than when it was not. Levels of serum cholesterol and pre-beta-lipoprotein were not affected by the supplementation of capsaicin. The perirenal adipose tissue weight was lower when capsaicin was present in the diet than when it was not. Hepatic enzyme activities of glucose-6 phosphate dehydrogenase and adipose lipoprotein lipase were lower in rats fed the 30% lard diet than in those fed a nonpurified diet. Activities of these two enzymes were higher when capsaicin was added to the diet than when it was not. Hepatic acetyl-CoA carboxylase, beta-hydroxyacyl-CoA dehydrogenase, and adipose hormone-sensitive lipase activities were not affected by capsaicin feeding. Lipid absorption was not affected by the supplementation of capsaicin. The perirenal adipose tissue weight and serum triglyceride were decreased as the level of capsaicin in the diet increased up to 0.021%. These results suggest that capsaicin stimulates lipid mobilization from adipose tissue and lowers the perirenal adipose tissue weight and serum triglyceride concentration in lard-fed rats. PMID- 2875142 TI - Activities of cerebral dihydropteridine reductase and tyrosine hydroxylase in chronic uremia in rats. AB - The effect of chronic uremia on activities of cerebral dihydropteridine reductase (DHPR) and tyrosine hydroxylase (TH) and content of norepinephrine and dopamine was investigated in the male Sprague-Dawley rats. The uremic animals were fed diets containing either 8% or 18% casein ad libitum, and sham-operated pair-fed and ad libitum fed animals were used as controls. There were no significant differences in TH activity between the groups fed the two levels of protein. Uremic rats had lower activity of TH than pair-fed controls, and pair-fed controls had lower activity than ad libitum-fed animals. DHPR activity and norepinephrine and dopamine content did not differ among the groups. Our study suggests that the chronic uremic condition or restricted feeding causes a decrease in brain TH activity which is not mediated by decreased DHPR activity. Further, this decreased enzyme activity does not result in depressed catecholamine content, indicating the presence of a highly regulated mechanism controlling catecholamine levels. PMID- 2875143 TI - A review of conscious sedation with orally administered benzodiazepines. PMID- 2875144 TI - Elucidation of cellular population and nature of anti-amoebic antibodies in cytotoxicity to Entamoeba histolytica (NIH:200). AB - Interactions between trophozoites of Entamoeba histolytica and cells of the immune system were studied in vitro by mixing effector cells obtained from normal and immunized guinea pigs with trophozoites in a ratio of 10:1. Crude amoebic extract (CAE) and its highest molecular weight (MW 650,000) fraction (F-I) were used for priming the effector cells in vivo. The effector cells were collected from the spleens of normal and immunized animals. Lymphocytes were prepared by allowing splenic mononuclear cells to adhere to plastic, followed by passage through nylon wool column. There was no significant difference between the killing capacity of mononuclear cells, monocyte depleted mononuclear cells or nylon wool fractionated lymphocytes, indicating that probably monocytes and B cells were not involved in the cytotoxicity against E. histolytica. The data suggest that effector cells probably belonged to the T-cytotoxic and K-cell category. Both CAE and F-I sensitization could induce cytotoxicity of lymphocytes against trophozoites. Similarly, anti-CAE and anti-F-I sera were found to enhance the killing capacity of effector cells in vitro. The ability of anti-amoebic serum to induce cytotoxicity was found to be independent of complement involvement and resided in IgG but not in IgM. PMID- 2875145 TI - Undescended testis: the effect of treatment on subsequent risk of subfertility and malignancy. AB - The literature was reviewed for information on the long-term effects of cryptorchidism on fertility and cancer incidence. In unilateral cryptorchidism, treatment policies of orchidopexy alone, or of human chorionic gonadotrophin (hCG) therapy followed, if necessary, by orchidopexy, have resulted in similar levels of reduced fertility (15% azoospermia, and an additional 30% oligospermia, ie, sperm count less than 20 X 10(6)/mL). Very similar results were observed in unilateral cryptorchid men who had had no treatment (and were still cryptorchid at semen examination). In contrast, no untreated bilaterally cryptorchid men have normal fertility (sperm count greater than 20 X 10(6)/mL), whereas of those treated, a quarter have normal fertility. In some series, as many as half of the bilateral cryptorchid testes descended following hormonal treatment; a finding that could be attributed, at least in part, to the frequent difficulty in deciding on clinical examination, whether these testes are truly cryptorchid. There is little evidence that operation early rather than late within the age range of 4 to 14 years has any effect on subsequent fertility. Histologic studies suggest that orchidopexy should be carried out before age 2, but there are almost no follow-up data with which to evaluate the results of early operation. Since there is evidence that orchidopexy may result in testicular atrophy in a small proportion of cases, a trial of luteinizing hormone-releasing hormone (LHRH) may be advisable. There is little information available concerning the effect of age at orchidopexy on the subsequent risk of testicular cancer. Testes that cannot be brought into the scrotum should be excised. PMID- 2875146 TI - A study of powder adhesion to metal surfaces during compression of effervescent pharmaceutical tablets. AB - Effervescent tablets were produced using four different formulations containing citric and/or tartaric acid and sodium bicarbonate with povidone and macrogol 6000. The same formulations were prepared with the addition of 1% sucrose ester powder. The adhesion of each formulation to the metal faces of tableting machine punch tips was determined using electron microscopy, surface roughness measurements and quantification of punch weight variations during tablet production. The basic formulations were inherently adhesive and produced tablets with a weak, porous structure which were qualitatively and quantitatively rougher than conventional, non-effervescent compressed tablets. Both formulations containing tartaric acid produced tablets with a lower surface roughness and with less tendency to stick to tablet punch faces than the two formulations containing citric acid alone. The addition of a water-soluble sucrose ester had a beneficial effect especially on the formulations with inherently high adhesive tendencies. PMID- 2875147 TI - Self-association of local anaesthetic drugs in aqueous solution. AB - The aggregation characteristics of a series of local anaesthetic drugs in water and electrolyte solution have been examined using total intensity light scattering, photon correlation spectroscopy and vapour pressure osmometry. The association of cinchocaine hydrochloride was micellar. An appreciable increase in the effective diffusion coefficient as solutions of cinchocaine were diluted close to the critical micelle concentration was observed and has been discussed. The association of amethocaine hydrochloride could be described using a co operative stepwise association model. No association could be detected in water or 0.1 mol dm-3 electrolyte for butacaine hemisulphate and the hydrochlorides of procaine, proparacaine, mepivacaine, lignocaine, bupivacaine and prilocaine at drug concentrations of less than 0.2 mol dm-3. PMID- 2875148 TI - Calculations of pH for complex mixtures of acids, bases and ampholytes. PMID- 2875149 TI - Non-ionic surfactant vesicles, niosomes, as a delivery system for the anti leishmanial drug, sodium stibogluconate. AB - Liver and serum concentrations of antimony in the mouse have been determined after administration of sodium stibogluconate in the free, liposomal and niosomal form. High liver and low serum values were attained by the use of both vesicular formulations. Niosomal sodium stibogluconate was shown to be more active than free drug against experimental murine visceral leishmaniasis, an effect apparently dependent on maintaining high drug levels in the infected reticuloendothelial system. PMID- 2875150 TI - Chromatographic separation of thioridazine sulphoxide and N-oxide diastereoisomers: identification as metabolites in the rat. AB - (+/-)-Thioridazine and (+/-)-desmethylthioridazine have been oxidized to produce a number of chiral sulphoxide and amine oxide compounds. Diastereoisomeric isomers were separated by thin-layer and high performance liquid chromatography. Thioridazine-5-sulphoxide, N-desmethylthioridazine-5-sulphoxide and thioridazine N-oxide diastereoisomers were found to be thioridazine metabolites following dosing in rats or after in-vitro incubation with rat liver homogenate. PMID- 2875151 TI - Electrokinetic properties of endotoxins and their significance for the limulus amoebocyte lysate test. AB - The electrokinetic properties of the endotoxins of Escherichia coli and Serratia marcescens have been examined. Both endotoxins are negatively charged, with the zetapotential being increased by the presence of cations whose relative influence resembles the Schulze-Hardy rule for colloid stability. Fe3+ and Th4+ ions are capable of reversing the negative charge of the endotoxin particles to positive. These cations were found to have a strong inhibitory effect on the activity of endotoxins in the limulus amoebocyte lysate test but the inhibitory effect did not parallel changes in the zetapotential because the effect occurred at concentrations too low to affect this parameter. PMID- 2875152 TI - Evaluation of the percutaneous absorption and metabolism of some aminopropiophenones. AB - The absorption of diethylpropion (DEP I), dimethylpropion (DMP I) and some of their basic metabolites into and passage through the skin was investigated and a comparison of their metabolism following oral and percutaneous administration made. High percentages (60-80%) of DEP I and its metabolites and a small percentage of DMP I and its metabolites were taken up into the skin in less than 2 min--the remaining percentages of the compounds were absorbed into the skin by a first order process. The rate of appearance of the compounds in the blood, which reflects their rate of passage through the skin, did not correlated with their rate of absorption into the skin. More metabolism occurred with all the compounds after their oral administration than after their percutaneous application. PMID- 2875153 TI - Locomotion and stereotyped behaviours induced by 1-amino-3,5-dimethyladamantane (D 145) and apomorphine in the rat: a comparison. AB - The locomotion and stereotyped behaviours induced by the two dopamine agonists, 1 amino-3,5-dimethyladamantane (D 145) and apomorphine in rats have been investigated using a holeboard apparatus. Unlike apomorphine, D 145 did not induce compulsive gnawing, but it did induce locomotion dose-dependently. However, the pattern of locomotion was different from that induced by apomorphine and the locomotion itself was potently antagonized by haloperidol but not by sulpiride; this is the opposite to apomorphine-induced locomotion. This indicates that locomotion induced by dopamine agonists is not a unitary phenomenon but that different 'types' of locomotion, with different pharmacological properties, can be induced. Low doses of D 145, given before apomorphine, reduced apomorphine induced gnawing and enhanced apomorphine-induced locomotion. The long lasting 'priming' effect known to occur after repetitive injections of apomorphine was not mimicked by D 145. Apomorphine and D 145 are considered to be two specific DA agonists; their behavioural-pharmacological profiles, however, are quite different. PMID- 2875154 TI - Brittle fracture propensity measurements on 'tablet-sized' cylindrical compacts. AB - The brittle fracture propensity test which was originally designed for large, square compacts with a central hole has been modified and extended to compacts of 'tablet-sized' dimensions. This allows a brittle fracture propensity (BFP) index to be measured at strain rates and conditions approaching those normally used in tableting. The BFP indices for microcrystalline cellulose, Tablettose and heavy magnesium carbonate were evaluated at punch velocities of 3.33 and 200 mm s-1 and found to be in good agreement with the results of previous workers. PMID- 2875155 TI - Localized cracking around pigment particles in tablet film coatings: a theoretical approach. AB - The problem of localized cracking around pigment particles in tablet film coatings has been treated as being analogous to stress cracking in two phase ceramics. For this purpose a simple model of a spherical cavity in an infinite isotropic medium has been used. As well as allowing the estimation of the stresses generated by the differences in thermal expansion of the dispersed pigment and the polymer matrix, the model predicts the effect of some formulation variables. The predictions are in agreement with the observed cracking on film coated tablets. PMID- 2875156 TI - The disposition of pyrimethamine in the rat isolated perfused liver: the effect of suramin. AB - The pharmacokinetics of pyrimethamine (0.5 mg) were determined in the rat isolated perfused liver in the presence of suramin (17.75 mg). The clearance, half life, area under the curve, and volume of distribution of pyrimethamine were unaffected by the concurrent administration of suramin, as was the hepatic sub cellular disposition of the drug. This report is of relevance to the future concurrent administration of suramin and pyrimethamine in West Africa. PMID- 2875158 TI - Saliva secretion of chloroquine in man. AB - The presence of chloroquine in saliva from seven healthy volunteers for 21 days after a single 600 mg oral dose of the drug was established by chromatographic and spectroscopic methods. The results showed the drug to be rapidly absorbed with a tmax in saliva of 3.9 +/- 1.6 h. A long elimination half-life of 7-20 days, calculated from the saliva concentration-time profile, is in agreement with values previously reported for the drug using plasma level data. In three of the volunteers from whom simultaneous blood samples were obtained, the mean Cs/Cp value was 1.20 +/- 0.27. It is suggested that saliva level determination may be used in evaluating patient compliance, therapeutic drug monitoring and pharmacokinetic parameters of chloroquine. PMID- 2875157 TI - Diuretic effect of L-threo-3,4-dihydroxyphenylserine, a noradrenaline precursor, in rats and mice. AB - L-Threo-DOPS, a noradrenaline (NA) precursor, produced a dose-dependent increase in the volume of urine in mice and rats. It also increased the total output of sodium and chloride ions, but not the excretion of potassium ion. Treatment with peripheral decarboxylase inhibitors antagonized not only the diuretic action, but also the increase in the concentration of kidney NA produced by L-threo-DOPS. These results suggest that the diuretic action of L-threo-DOPS might not be due to its direct action, but largely to NA formed by its decarboxylation in the kidney. PMID- 2875159 TI - Hyperphagia caused by muscimol injection in the nucleus raphe dorsalis of rats: its control by 5-hydroxytryptamine in the nucleus accumbens. AB - Muscimol injection in the nucleus raphe dorsalis caused intense eating by rats with access to food. A dose-related reduction of muscimol's effect was found after bilateral injections of 5-hydroxytryptamine (5-HT) in the nucleus accumbens (dose range 2.2-8.8 micrograms in 2 microliter) but no effect was observed when an even higher dose (17.6 micrograms) of 5-HT was injected in the caudate putamen. Eating by food-deprived rats was not changed by any dose of 5-HT injected either into the nucleus accumbens or the caudate putamen. (+) Norfenfluramine, 20 micrograms, injected in the nucleus accumbens also reduced muscimol-induced eating but had no effect on the food intake of starved rats. The results suggest an important role of 5-HT in the nucleus accumbens in the control of certain types of hyperphagia in rats. PMID- 2875160 TI - Effects of chloroquine and didesethylchloroquine on rabbit myocardium and mitochondria. AB - The effects of chloroquine and didesethylchloroquine on the rabbit isolated perfused heart and on calcium binding and accumulating ability of the heart mitochondria were investigated. The drugs produced negative chronotropy, negative inotropy and a decrease in coronary flow rate in the isolated perfused myocardium. Both chloroquine and didesethylchloroquine significantly decreased mitochondrial calcium binding and accumulation. These results suggest that the cardiodepressant actions of chloroquine could be due in part to alterations in the calcium accumulating abilities of the mitochondrial membranes, and that didesethylchloroquine, among other metabolites, does contribute significantly to the total observed effect of chloroquine on the cardiovascular system. PMID- 2875161 TI - The ability of amine N-methyltransferases from rabbit liver to N-methylate azaheterocycles. AB - The substrate specificity of two homogeneous amine N-methyltransferases from rabbit liver has been demonstrated to extend to the azaheterocycles pyridine, R (+)-nicotine and S-(-)-nicotine. Both enzymes methylate R-(+)-nicotine at the pyridyl nitrogen to afford the N-methylnicotinium salt, whereas S-(-)-nicotine does not act as a substrate for either enzyme. Surprisingly, R-(+)-nicotine is methylated at either the pyridyl nitrogen, or the pyrrolidine nitrogen, to afford the two isomeric monomethylate nicotinium ions when an enzymic preparation containing both methyl transferase activities was used. Under similar conditions S-(-)-nicotine was methylated only at the pyridyl nitrogen. The production of charged metabolites in-vivo, from the large number of pyridino-compounds that are used as drugs, or are present in the environment, may be of toxicological significance, in view of the reported toxicities of several such quaternary ammonium compounds. PMID- 2875162 TI - Evidence against leukotriene-mediation of propranolol-induced airway hyperreactivity to acetylcholine. AB - In unanaesthetized guinea-pigs, propranolol treatment (0.1 mg kg-1 i.v.) substantially increased reactivity to intravenous acetylcholine infusion or aerosolized histamine to a comparable degree. Neither BW755c (5 mg kg-1 i.v.), FPL 55712 (1 mg kg-1 i.v.), nor piriprost (5 mg kg-1 i.v.) pretreatment influenced propranolol's effect on muscarinic reactivity although BW755c abolished histaminic hyperreactivity. This suggests that propranolol-induced muscarinic hyperreactivity in the guinea-pig is not mediated by leukotrienes whereas histaminic hyperreactivity may be. PMID- 2875163 TI - Tetrodotoxin inhibits directly acting stimulants of intestinal fluid secretion. AB - Intravenous injection of tetrodotoxin (20 micrograms kg-1) to anaesthetized rats blocks PGE1- and inhibits VIP-induced fluid secretion from the mucosa of the jejunum without affecting the physiological rates of net water and glucose absorption. It is suggested that the toxin might release an endogenous inhibitor of secretion or that it might possess direct antisecretory activity on the epithelial cells of the jejunum. It is further suggested that results where tetrodotoxin has been used to investigate secretagogue action should be treated with caution. PMID- 2875164 TI - Clonidine reduces plasma melatonin levels. AB - Clonidine, an alpha-adrenoceptor agonist, reduces human plasma melatonin levels when administered intravenously at 2-3 micrograms kg-1 to sleeping volunteers. Measurement of plasma melatonin levels after administration of clonidine could be the basis for a clinical in-vivo test of alpha-adrenoceptors. PMID- 2875165 TI - Variability of the blood/plasma concentration ratio of pethidine. PMID- 2875166 TI - Effect of TRH on acid secretion in the mouse stomach. PMID- 2875167 TI - Statistical analysis of gastrointestinal transit time of pharmaceutical formulations: comments on the letter by Devereux & Newton. PMID- 2875168 TI - Behavioral studies with anxiolytic drugs. III. Antipunishment actions of buspirone in the pigeon do not involve benzodiazepine receptor mechanisms. AB - Buspirone, a clinically effective anxiolytic, has not shown robust effects consistently in procedures used traditionally with rodents and nonhuman primates to evaluate potential antianxiety activity. When key pecking by pigeons was maintained by food and was punished alternately under one component of a multiple schedule by the presentation of electric shock (conflict procedure), buspirone (0.03-10.0 mg/kg i.m.) produced increases in punished responding that were up to 30 times those of the control response rate. These doses did not affect or decreased unpunished responding. A buspirone analog, MJ 13805 (gepirone) produced effects similar to buspirone, although unpunished responding was slightly more sensitive to the rate-decreasing effects of MJ 13805 than to those of buspirone. A metabolite of buspirone, 1-pyrimidinyl piperazine (1-PP; MJ 13653), did not affect key pecking across a wide dose range (0.01-3.0 mg/kg i.m.), although slight decreases in both punished and unpunished responding occurred at the highest dose. Increases in punished responding with buspirone were not affected by the benzodiazepine receptor antagonist Ro 15-1788 (0.01-0.1 mg/kg i.m.). [3H]Diazepam binding to pigeon cerebrum or cerebellum in vivo was not altered by buspirone, or did buspirone, MJ 13805, or 1-pyrimidinyl piperazine displace [3H]flunitrazepam binding in vitro at pharmacologically relevant concentrations. These findings confirm previous work demonstrating marked rate-increasing effects of buspirone on punished responding in the pigeon, extend such effects to the buspirone analog MJ 13805 and indicate that the effects of buspirone are not mediated through the benzodiazepine receptor complex. PMID- 2875169 TI - Effects of cholinergic blockade, adrenergic blockade and sympathetic denervation on gastrointestinal myoelectric activity in guinea pig. AB - Gastrointestinal myoelectric activity was recorded from conscious guinea pigs using sets of bipolar electrodes that had been surgically implanted onto the serosal surface of the gastric antrum or small intestine. The role of nerves in the control of the migrating myoelectric complex (MMC) was investigated using cholinergic and adrenergic receptor antagonists, guanethidine to block sympathetic transmission, reserpine to deplete intestinal monoamines and 6 hydroxydopamine (6-OHDA) to produce chemical sympathectomy and surgical sympathetic denervation of the stomach and small intestine. Subcutaneous infusion of hyoscine (1.0 or 3.0 mg/kg and 1.0 or 3.0 mg/kg/hr) blocked the initiation of phase 3 of the MMC. In the presence of hyoscine, intermittent electrical spiking comparable to that of phase 2 of the MMC was recorded. Hexamethonium infusion (3.0 or 10.0 mg/kg and 3.0 or 10.0 mg/kg/hr) also blocked the initiation of phase 3 and reduced the frequency of the intermittent spiking activity. Acute blockade of adrenergic receptors by simultaneous s.c. infusion of phentolamine and propranolol (1.0 mg/kg and 1.0 mg/kg/hr of each drug) did not alter the MMC, whereas infusion of guanethidine (3.75 or 7.5 mg/kg and 3.75 or 7.5 mg/kg/hr) increased the frequency of the MMC by significantly shortening the duration of phase 2. Sympathetic denervation of the stomach and small intestine did not block the MMC but decreased the cycle frequency by significantly prolonging the duration of phase 2. Chemical sympathectomy using 6-OHDA treatment (3 X 250 mg/kg s.c.) also did not abolish the MMC but decreased the frequency by increasing the duration of phase 2. Reserpine treatment (2.5 mg/kg s.c.) decreased the frequency of the MMC to a greater extent than that produced by 6-OHDA treatment. Histochemical and immunohistochemical evaluation of tissues taken from denervated, 6-OHDA- and reserpine-treated animals confirmed that surgical denervation removed sensory and adrenergic nerves to the stomach and small intestine, whereas chemical sympathectomy affected only adrenergic neurons. Reserpine treatment depleted norepinephrine from extrinsic adrenergic neurons and also depleted 5-hydroxytryptamine from intrinsic intestinal neurons. In the guinea pig, antral myoelectric activity is briefly inhibited during duodenal phase 3. Gastric inhibition persisted during duodenal phase 3 in surgically denervated animals, in 6-OHDA-treated animals and in animals treated acutely with guanethidine. These results indicate that extrinsic sensory and sympathetic nerves are not required for the initiation and propagation of the MMC in the guinea pig small intestine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2875170 TI - Opioid agonist activity of ICI 174864 and its carboxypeptidase degradation product, LY281217. AB - The opioid peptide antagonist, ICI 174864 ([allyl]2-Tyr-alpha-amino-isobutyric acid (Aib)-Aib-Phe-Leu-OH), can produce analgesic effects in mice. The present study explored the possibility that ICI 174864 1) may have affinity and agonist efficacy at mu receptors and/or 2) may form a carboxypeptidase degradation product in vivo that possesses mu agonist activity. In vitro, ICI 174864 (10(-7) to 10(-4) M) inhibited the twitch in the electrically stimulated mouse vas deferens (ED50 = 90 microM) and guinea pig ileum (ED50 greater than 10(-4) M). The in vitro partial agonist activity of ICI 174864 was due to interaction with delta and not mu receptors because the apparent dissociation constant for naloxone using ICI 174864 as the agonist was similar to the apparent dissociation constant for the interaction of naloxone with delta and not mu receptors. Thus, ICI 174864 is a weak partial agonist at delta receptors with little affinity or efficacy at mu receptors. The incubation of ICI 174864 with carboxypeptidase A generated a peptide, LY281217 [(allyl)2-Tyr-Aib-Aib-Phe-OH], which was a more potent agonist in the mouse vas deferens and guinea pig ileum than ICI 174864. The agonist activity of LY281217 was due to interaction with mu and not delta receptors because LY281217 was approximately 100-fold more potent than ICI 174864 as an agonist in the guinea pig ileum, the apparent dissociation constant for naloxone using LY281217 as the agonist was similar to the apparent dissociation constant for the interaction of naloxone with mu receptors and the delta selective antagonist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875171 TI - Corticotropin-releasing factor inhibits neurogenic plasma extravasation in the rat paw. AB - Increased exudation of plasma proteins, as measured by Evans blue leakage into the innervated paw, was produced by antidromic stimulation of the saphenous nerve in the pentobarbital-anesthetized rat. This condition, termed neurogenic plasma extravasation (NPE), was inhibited by morphine, FK 33,824 (a stabilized enkephalin analog), dynorphin (1-13), dynorphin(1-10)amide and corticotropin releasing factor (CRF) at median effective doses of 2700, 0.45, 1180, 4050 and 5.6 nmol/kg i.v., respectively. The inhibitory effect of CRF was present when injected up to 60 min before electrical stimulation of the nerve. By contrast, the effects of morphine and FK 33,824 were shorter in duration, lasting for only 20 to 30 min before nerve stimulation. Inhibition of NPE by morphine, FK 33,824 dynorphin (1-13) and dynorphin (1-10)amide was blocked by naloxone, 1 mg/kg i.v., but the CRF inhibition was not affected. CRF inhibited NPE in both hypophysectomized and adrenalectomized rats, indicating that its effects were not due to secondary release of endogenous opioid peptides. The inhibitory effect of CRF on NPE was also separable from its hypotensive properties and could be obtained at intradermal doses of CRF into the paw skin which were approximately 11 times lower than the i.v. doses. Intracerebroventricular injection of CRF did not affect the tail-flick latency of rats to warm water. CRF administered i.v. in mice did, however, inhibit writhing responses to phenylbenzoquinone (PBQ), suggesting possible peripheral antinociceptive properties. PMID- 2875172 TI - Dynorphin A and related peptides administered intrathecally in the rat: a search for putative kappa opiate receptor activity. AB - The intrathecal delivery of dynorphin A (1-17) and (1-13) induces, with rapid onset, a severe motor dysfunction characterized by flaccid extension of the hindlimbs and complete loss of muscle tone. This motor effect does not appear to be mediated via opiate receptors as high doses of naloxone neither block nor reverse motor dysfunction, and it is produced by dynorphin A fragments inactive at opiate receptors. At doses just below those which produce motor dysfunction, dynorphin A has no effect on nociceptive responses in the hot-plate, tail-flick and writhing tests. The selective, kappa opiate agonist, U50488H, produces a significant, dose-dependent inhibition of writhing, which is antagonized by pretreatment with naloxone, but has no effect on hot-plate and tail-flick latency. The kappa agent U50488H does not produce motor dysfunction with doses as high as 300 nmol/rat. It appears that the potent kappa opiate activity exhibited by dynorphin A in vitro may not reflect in vivo effects of dynorphin after intrathecal administration. PMID- 2875173 TI - Beta adrenergic receptor subtypes in the atria: evidence for close coupling of beta-1 and beta-2 adrenergic receptors to adenylate cyclase. AB - The relationship between occupancy of beta adrenergic receptors and stimulation of adenylate cyclase in dog atrial tissue was examined by studying the binding of [125I]iodopindolol and the activation of adenylate cyclase. Computer-assisted nonlinear regression analysis was used to analyze the inhibition of isoproterenol stimulated adenylate cyclase activity by beta-1- or beta-2-selective antagonists. The Ki values for each subtype of receptor for the selective antagonists resulting from studies of the inhibition of adenylate cyclase activity were similar to those determined in studies of the inhibition of the binding of [125I]iodopindolol. To compare further the occupancy of beta-1 or beta-2 adrenergic receptors with the activation of adenylate cyclase mediated by each class of receptor, computer modeling of the stimulation of adenylate cyclase by the beta-1-selective agonist norepinephrine was carried out. The EC50 values of norepinephrine for each receptor subtype, as measured in studies of norepinephrine-stimulated adenylate cyclase activity, were similar to the Ki values for the inhibition by norepinephrine of the binding of [125I]iodopindolol to each receptor subtype. The data led to the conclusion that beta-1 adrenergic receptors make up about 70% of the total number of beta adrenergic receptors and mediate 70% of the increase in adenylate cyclase activity produced by isoproterenol. These results suggest that the relationship between occupancy of each class of receptor and activation of adenylate cyclase is linear and that, when agonist-stimulated adenylate cyclase activity is used as a functional response, neither spare beta-1 nor spare beta-2 adrenergic receptors exist in the atrium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875174 TI - Characterization of the inhibition of excitatory amino acid-induced neurotransmitter release in the rat striatum by phencyclidine-like drugs. AB - In the present study, the authors found that, in Mg++-free buffer, N-methyl-D aspartate (NMDA) was able to evoke the Ca++-dependent and tetrodotoxin-sensitive release of striatal acetylcholine (ACh), presumably via interaction with receptors on cholinergic interneurons. In Mg++-free buffer containing pargyline, NMDA also evoked a Ca++-dependent and tetrodotoxin-sensitive release of striatal [3H]dopamine (DA). Phencyclidine (PCP) and physiological concentrations of Mg++ (1.2 mM) also inhibited ACh release evoked by L-glutamate, L-aspartate and DL homocysteate, but not ACh release evoked by the glutamate analogs quisqualate and kainate, suggesting that PCP is selective for the magnesium-sensitive, NMDA preferring glutamate-aspartate receptor subtype. Comparison of PCP inhibition of NMDA-stimulated ACh and DA release with that produced by the competitive NMDA antagonist 2-amino-5-phosphonovalerate indicates that PCP is probably not altering release by a direct action on the NMDA recognition site. The ability of 2-amino-5-phosphonovalerate, but not PCP, to prevent desensitization of NMDA induced ACh release is consistent with this interpretation. Binding studies did, however, reveal a reduction in the apparent affinity of the PCP binding site by high concentrations of NMDA. This may suggest an allosteric link between the PCP sigma receptor and the NMDA-type glutamate-aspartate receptor. The receptors mediating excitatory amino acid-induced DA release were somewhat less selective than those on cholinergic neurons in their sensitivity to both Mg++ and PCP. Structure-activity-relationship studies suggested that the inhibition off ACh and DA release evoked by NMDA involves biding to the PCP-sigma receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875175 TI - Alpha adrenoceptor antagonists selectively reduce thrombin-stimulated contraction in rabbit arteries. AB - Thrombin-induced contractions and the influence on them of alpha adrenoceptor antagonists were studied in the rabbit femoral and central ear artery using in vitro methods. Maximum contraction with thrombin represented between 50 and 66% of the maximum arterial response to norepinephrine (NE). The thrombin dose response relationship was complex and did not have a classic sigmoidal shape, whether the endothelium was functional or not. In the femoral artery, the nonselective alpha adrenoceptor antagonist phentolamine (10(-6) M) and the selective alpha-1 adrenoceptor antagonist prazosin (10(-8) and 10(-7) M) significantly reduced the contractions induced with concentrations of thrombin greater than 6 U X ml-1, and increased the concentration of thrombin required to produce maximal contraction. The selective alpha-2 adrenoceptor antagonist rauwolscine (10(-7) M) did not alter the contraction initiated by thrombin or by NE. In the rabbit ear artery, contraction to thrombin and NE could also be reduced with prazosin but not rauwolscine. Reserpine pretreatment did not alter the magnitude of the thrombin-induced contraction in the femoral and central ear artery, indicating that the response and its sensitivity to alpha adrenoceptor blockade was not related to the release of NE from nerve stores. Neither thrombin (0.1-16 U X ml-1) nor NE (10(-9)-10(-5) M) produced any significant relaxation in partially contracted rabbit femoral arteries, whether or not the endothelium was functional, i.e., exhibiting a 50 to 100% maximum relaxation with methacholine or when either alpha-1, alpha-2 or beta adrenoceptor antagonists were present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875176 TI - Dynorphin effects on plasma concentrations of anterior pituitary hormones in the nonhuman primate. AB - The role of dynorphin-(1-13) and dynorphin-(1-10)-amide in the neuroendocrine control of primate anterior pituitary hormones was studied in nonrestrained, ovariectomized rhesus monkeys. The effects of these opioids on plasma concentrations of prolactin (PRL), luteinizing hormone (LH), follicle stimulating hormone (FSH) and thyrotropin (TSH), and interactions with naloxone are reported here. Intravenous administration of dynorphin-(1-13), 30 to 120 micrograms/kg, significantly increased plasma PRL levels 3- to 4-fold. These PRL increases occurred within 5 min and levels remained elevated for at least 60 min. Administration of naloxone (1.0 mg/kg i.v.) antagonized the rise in PRL levels. Dynorphin-(1-13) had no significant effect on plasma LH, FSH or TSH levels. Dynorphin-(1-10)-amide (30-120 micrograms/kg) increased plasma PRL levels 2- to 4 fold at 5 to 40 min after administration. Plasma LH levels were significantly depressed 100 to 120 min postdrug. Dynorphin-(1-10)-amide produced no change in plasma FSH or TSH levels. These results indicate that dynorphin is involved in the modulation of PRL and perhaps LH secretion, although not affecting TSH or FSH release. PMID- 2875177 TI - Lanthanum as a surrogate for calcium in transmitter release at mouse motor nerve terminals. AB - The mechanism by which lanthanum (La3+) causes an increased frequency of miniature end-plate potentials (m.e.p.p.s) was studied at the mouse neuromuscular junction. At concentrations as low as 0.25 microM, La3+ caused a progressive rise in m.e.p.p. frequency, to a maximum of several hundred per second. 'Washing' with solution containing EDTA arrested the rise, but did not substantially reduce the raised m.e.p.p. frequency. At partially 'lanthanized' junctions high frequencies of m.e.p.p.s were maintained indefinitely, even in 0 Ca2+/EDTA solutions. The rate of development of high m.e.p.p. frequency was increased by repetitive nerve stimulation or by depolarization of the nerve terminal (high K+ or focally applied current), and appeared to be proportional to the concentration of La3+ over the range of 0.25-5 microM. At low concentrations of La3+ the rise of m.e.p.p. frequency depended upon the co-presence of a small amount of Ca2+ (greater than 10 microM) and was slowed and partially blocked by Cd2+, or by Ca2+ at about 10 microM. The quantal content of end-plate potentials was usually reduced in the presence of La3+, but was increased over control values after removal of La3+ by 'washing' with solution containing EDTA, once a raised m.e.p.p. frequency had developed. At partially lanthanized junctions the absolute increases in m.e.p.p. frequency produced by Ca2+ (in raised K+), ethanol, or by nerve stimulation in the presence of Ba2+, were greater than at control junctions, but in each case the increases in the logarithm of m.e.p.p. frequency were less than at control junctions. It is concluded that La3+ causes transmitter release only after entry into the nerve terminal via voltage-sensitive channels, probably those that normally admit Ca2+, that La3+ and Ca2+ may co-operate at internal sites to induce transmitter release, and that these ions both co-operate and compete at external sites that regulate their entry into the nerve terminal. PMID- 2875178 TI - A physiological basis for subclassifying beta-adrenoceptors examined by chemical sympathectomy of guinea-pigs. AB - Chemical sympathectomy of guinea-pigs was induced by chronic pretreatment with 6 hydroxydopamine over a 20 day period. Control animals were sham injected with vehicle at the same times. Isolated tissues were removed from the animals and beta-adrenoceptor sensitivity assessed from cumulative concentration-response curves for isoprenaline, followed after wash-out by a partial agonist (salbutamol, ritodrine or prenalterol). The following responses were measured: increases in force and rate of contraction of left and right atria respectively, inhibition of carbachol-induced ileal contractions, relaxation of intrinsic tone of lung strips and tracheal spirals, inhibition of contractions of vas deferens and soleus muscle induced by field stimulation. Left and right atria and ileum from 6-hydroxydopamine-pretreated guinea-pigs exhibited supersensitivity to beta adrenoceptor stimulation. This was measured as a leftwards shift of the concentration-response curve for isoprenaline and as an elevation of the partial agonist maximum response (relative to isoprenaline), when compared with tissues from sham-injected controls. The supersensitivity was assumed to be due to the loss of endogenous neurotransmitter release by chemical sympathectomy and specific for the beta-adrenoceptor. In contrast, lung strips, vas deferens and soleus muscle were not supersensitive. The responses of these tissues are thought to be mediated via beta 2-adrenoceptors whereas cardiac and ileal responses are beta 1-adrenoceptor mediated. The latter receptor subtype would therefore appear to be under the influence of sympathetic innervation, but since no supersensitivity occurred at beta 2-adrenoceptors these were presumed to be non innervated but stimulated by circulating adrenaline. These results obtained by use of chemical sympathectomy with 6-hydroxydopamine support the contention that the physiological basis of beta-adrenoceptor subclassification is that the beta 1 subtype are innervated whereas the beta 2-subtype are non-innervated. PMID- 2875180 TI - A quantitative study of preporcelain soldered connector strength with palladium based porcelain bonding alloys. PMID- 2875181 TI - Analysis of antigens from membrane and soluble fractions of Entamoeba histolytica. AB - Axenic cultures of Entamoeba histolytica strains HK-9, HM-1, and Rahman were fractionated to provide plasma membranes, internal, vesiculated membranes, and a soluble cytosol. Each particulate fraction was solubilized and all fractions were analyzed by techniques designed to demonstrate molecular complexity and serologic reactivity. The cytosol contained more antigenic moieties than either membrane fraction; however, the antigens associated with the membranes had very high reactivity and lower nonspecific activity than the cytosol. PMID- 2875179 TI - Miniature and evoked inhibitory junctional currents and gamma-aminobutyric acid activated current noise in locust muscle fibres. AB - gamma-Aminobutyric acid (GABA) current noise and inhibitory junctional currents (i.j.c.s) have been examined to give properties of the GABA receptor and its associated synaptic channel. Various procedures were used to identify muscle bundles receiving inhibitory innervation. In normal bathing medium the decay time constant of the i.j.c. was tau i.j.c. = 7.6 +/- 0.7 ms (clamp potential, Vm = -80 mV; temperature, T = 21 degrees C). Most muscle fibres were sensitive to ionophoretically applied GABA, irrespective of the presence of inhibitory innervation. GABA current noise obtained at junctional sites gave spectra which were fitted usually with a single Lorentzian component, or occasionally with the sum of two Lorentzians. The conductance of the single inhibitory channel was, gamma (GABA) = 21.6 +/- 0.9 pS (Vm = -80 mV; T = 21 degrees C). The mean 'burst length' of the openings produced by a single receptor activation was tau noise = 4.0 +/- 0.8 ms, at Vm = -80 mV. This decreased exponentially with hyperpolarization. On average tau i.j.c. exceeded tau noise although good agreement was found in some fibres. I.j.c.s were examined in greater detail after excitatory synaptic receptors had been desensitized with 10(-3) M-L-glutamate to abolish all excitatory synaptic activity. Their decay time constant was tau i.j.c. = 7.2 +/- 0.4 ms, and their rise time was 3.3 +/- 0.12 ms, at Vm = -80 mV. An e-fold decrease in tau i.j.c. resulted from a 103 +/- 7.9 mV hyperpolarization; time to peak showed a smaller dependence on Vm. The mean size of the inhibitory quantal event (i.e. response to a single transmitter packet) was estimated from fluctuations in i.j.c. amplitude. Mean quantal content of the i.j.c. was about 30 at normal levels of release. Mean amplitude of the directly measured miniature i.j.c. = 0.65 +/- 0.08 nA at Vm = -80 mV (V eq approximately equal to -40 mV). The amplitude of the quantal event showed a non-linear dependence on Vm. The burst length of the inhibitory channel, produced by a single receptor activation, is longer in duration (at -80 mV) and exhibits greater voltage dependence than the burst length of the excitatory glutamate activated channel in these fibres. It is estimated that a single quantum of GABA opens about 600-1000 post-synaptic chloride channels. PMID- 2875182 TI - Syntheses and beta-adrenergic agonist and antiaggregatory properties of N substituted trimetoquinol analogues. AB - Trimetoquinol [1-(3,4,5-trimethoxybenzyl)-6,7- dihydroxy-1,2,3,4 tetrahydroisoquinoline, TMQ] is a potent beta-adrenergic receptor agonist and inhibitor of human platelet aggregation. Selective cleavage of O-benzyl groups in the presence of an N-benzyl group using HCl and formation of a cyclic sulfite ester from the reaction of a catechol with thionyl chloride were achieved. The N substituents included methyl, benzyl, and beta-hydroxy- and beta-chloroethyl groups. Each N-substituted TMQ caused a concentration-dependent stimulation of beta 2 (trachea) and beta 1 (atria) adrenoceptor tissues and inhibition of 15(S) hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13(E)-dienoic acid (U46619, a thromboxane A2 mimetic) mediated human platelet activation. TMQ remained the most potent in the series. Structure-activity results indicated that the larger the N substituent, the lower the beta-adrenergic activity but the higher the inhibition of platelet aggregatory activity. Thus, the structural requirements of these TMQ analogues for the two types of biological activity are different. PMID- 2875183 TI - Synthesis and dopaminergic activity of some halogenated mono- and dihydroxylated 2-aminotetralins. AB - In a series of 7,8-dihydroxy-1-phenyltetrahydro-3-benzazepine dopamine receptor agonists introduction of a chloro or fluoro substituent into the 6-position increases dopaminergic potency. Also, in this series replacement of the 7 hydroxyl group with a halogen results in inversion of activity from dopamine receptor agonist to antagonist. The present study was aimed at exploring the possibility that the structure-activity observations in the 3-benzazepine series of dopaminergic agents might be extrapolated to another class of dopamine receptor agonists, the 2-aminotetralins. Thus, a series of chloro- and fluoro substituted mono- and dihydroxylated 2-aminotetralins was prepared and evaluated for dopaminergic properties in D-1 and D-2 receptor-related tests. Introduction of a chloro substituent into the 8-position of the prototype of this series, i.e. 2-amino-6,7-dihydroxytetralin (ADTN), resulted in a compound with a high degree of selectivity for the D-1 subpopulation of dopamine receptors; it was equally or more potent than ADTN in the D-1 receptor-related tests with greatly decreased effectiveness in the tests involving D-2 receptors. A similar effect was observed with 8-fluoro-ADTN; however, the N-(4-hydroxyphenethyl)-N-propyl derivative 4g of the 8-chloro-substituted ADTN showed marked D-2 binding affinity. Conversely, introduction of a chloro substituent into the 5-position of ADTN markedly decreased D-1 receptor affinity and efficacy. This effect was not seen with the related 5-fluoro derivative, suggesting D-1 receptors are more sensitive to bulk in the 5-position of ADTN than are the D-2 receptors. Replacement of either the 6 or 7-hydroxyl groups of ADTN with a chloro or fluoro substituent, in contrast, did not parallel the response seen in the benzazepine series (i.e., the compounds uniformly demonstrated less receptor affinity and did not have dopamine receptor antagonist activity); however, the decrease in agonist potency was less marked in the case of 2-amino-6-fluoro-7-hydroxytetralins than in the chlorinated monohydroxyaminotetralins. Thus, a parallelism in structure-activity relationships in the benzazepine and aminotetralin series of dopamine receptor agonists was not observed. The differences may reflect altered modes of receptor binding in the two series. PMID- 2875184 TI - (5-Amino-1,3-dimethyl-1H-pyrazol-4-yl)(2-fluorophenyl)methanones . A series of novel potential antipsychotic agents. AB - (5-Amino-1,3-dimethyl-1H-pyrazol-4-yl)(2-fluorophenyl)methanone (1) was found to have an antipsychotic-like profile in behavioral tests predictive of antipsychotic efficacy but, unlike available antipsychotic agents, did not bind in vitro to dopamine receptors. Upon further evaluation, 1 was found to cause clonic seizures in aged rodents. An examination of related structures revealed that 5-(substituted aminoacetamide) analogues of 1 shared this novel pharmacology and did not cause seizures. The synthesis and pharmacological evaluation of this series of compounds are described. Two compounds, 2-(diethylamino)acetamide (25) and 2-[[3-(2-methyl-1-piperidinyl)propyl]-amino]acetamide (38), were selected for examination in secondary tests. Like known antipsychotics both compounds reduced spontaneous locomotion in mice at doses that did not cause ataxia and inhibited conditioned avoidance selectively in both rats and monkeys. Unlike known antipsychotics neither 25 nor 38 elicited dystonic movements in haloperidol sensitized cebus monkeys, a primate model of antipsychotic-induced extrapyramidal side effects. Biochemical studies indicated that these compounds act via a nondopaminergic mechanism. Neither 25 nor 38 bound to dopamine receptors in vitro or caused changes in striatal dopamine metabolism in vivo. In addition, they did not raise serum prolactin levels as do known antipsychotics. Although adverse animal toxicological findings have precluded clinical evaluation of these agents, the present results indicate that it is possible to identify at the preclinical level nondopaminergic compounds with antipsychotic-like properties. PMID- 2875186 TI - Effect of methoxy substitution on the adrenergic activity of three structurally related alpha 2-adrenoreceptor antagonists. AB - We have recently reported the synthesis and alpha 2-antagonist activity of the methoxy derivative 2 [2-(2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline] and described the enhanced potency of this compound over the parent 1,4-benzodioxan, idazoxan, in reversing the inhibition caused by alpha 2-adrenoreceptor agonists of the electrically induced twitch in the rat or mouse vas deferens. It was of interest to us to discover whether a similar substitution in the structurally related alpha 2-adrenoreceptor antagonists piperoxan, prosympal, and fenmetazole would similarly enhance potency. We subsequently discovered that this was not so and potency was decreased markedly. In particular, that of the methoxy derivative of piperoxan was ca. 220 times less than the parent structure. PMID- 2875185 TI - Thiazole-4-carboxamide adenine dinucleotide (TAD). Analogues stable to phosphodiesterase hydrolysis. AB - Thiazole-4-carboxamide adenine dinucleotide (TAD), the active metabolite of the oncolytic C-nucleoside tiazofurin (TR), is susceptible to phosphodiesteratic breakdown by a unique phosphodiesterase present at high levels in TR-resistant tumors. Since accumulation of TAD, as regulated by its synthetic and degradative enzymes, appears to be an important determinant for sensitivity to the drug, a series of hydrolytically resistant phosphonate analogues of TAD were synthesized with the intent of producing more stable compounds with an ability to inhibit IMP dehydrogenase equivalent to TAD itself. Isosteric phosphonic acid analogues of TR and adenosine nucleotides were coupled with activated forms of AMP and TR monophosphate to give dinucleotides 2 and 4. Coupling of protected adenosine 5' (alpha, beta-methylene)diphosphate with isopropylidene-TR in the presence of DCC afforded compound 3 after deprotection. These compounds are more resistant than TAD toward hydrolysis and still retain potent activity against IMP dehydrogenase in vitro. beta-Methylene-TAD (3), the most stable of the TAD phosphonate analogues, produced a depletion of guanine nucleotide pools in an experimentally induced TR-resistant P388 tumor variant that was superior to that obtained with TR in the corresponding sensitive line. PMID- 2875187 TI - Survey of physician's assistant programs in the United States. PMID- 2875188 TI - Potent antagonism of Escherichia coli, Bacteroides ovatus, Fusobacterium varium, and Enterococcus faecalis, alone or in combination, for enteropathogens in anaerobic continuous flow cultures. AB - Interactions between representative strains of four predominant resident bacteria of the human colon, Escherichia coli, Enterococcus faecalis, Bacteroides ovatus, and Fusobacterium varium, and strains of seven enteropathogens, Yersinia enterocolitica, Shigella flexneri, Salmonella typhimurium, Vibrio parahaemolyticus, V. cholerae serogroup non O1, Staphylococcus aureus, and Clostridium perfringens, were examined in studies with an anaerobic continuous flow culture system and medium resembling the content of the mouse caecum (MCM). Potent unilateral antagonism attributable to synergic activities of the resident bacteria against the enteropathogens was evident. The four resident bacteria persisted at levels of c. 10(6) cfu/ml or more in single and in any mixed cultures of the resident species. The seven enteropathogens also persisted in single cultures. In contrast, Y. enterocolitica was excluded in several days in mixed cultures with each of the four resident bacteria. Sh. Flexneri and Staph. aureus were excluded in the presence of E. coli alone. C. perfringens, V. parahaemolyticus and V. cholerae serogroup non O1 were excluded in the presence of E. coli with B. ovatus and, in some cases, with additional species. S. typhimurium was the most resistant; only c. 10(2)-fold reduction of the population level was observed in mixed culture with all four of the resident species. When the amounts of some components in the medium, such as peptone and yeast extract, were increased, C. perfringens grew and persisted even in the presence of the four resident bacteria. Sh. flexneri, in contrast decreased steadily, even in enriched media. PMID- 2875189 TI - The effects of fimbriate and non-fimbriate strains of Escherichia coli on the oxidative reactions of neutrophils from a variety of species. AB - 5 fimbriate strains and 5 non-fimbriate strains of Escherichia coli were tested for their ability to enhance the cyanide insensitive oxygen consumption of human, bovine and ovine blood neutrophils in the absence of serum opsonins. Neutrophils from all 3 animal species showed significantly increased oxygen consumption when challenged with fimbriate strains. Only ovine neutrophils were stimulated by non fimbriate strains although to a lesser extent than by fimbriate strains. In the presence of serum the stimulation of ovine neutrophils was the same whether fimbriate or non-fimbriate strains were used. PMID- 2875190 TI - Cyclic AMP in normal and sympathetically aneural chick hearts during development. AB - Basal levels of cyclic adenosine monophosphate (cAMP) were measured in embryonic chick hearts at various times during development. Basal cAMP was highest on incubation day 5 and decreased throughout the remaining incubation period. Cyclic AMP could not be stimulated above basal level by intravenous in ovo administration of isoproterenol or tyramine on incubation day 5; however, there was a decrease in cAMP 2 mins after intravenous injection which was identical to the decrease in cAMP in controls injected with saline. Heart rate decreased following intravenous injection of saline on incubation day 5, but a similar decrease was not observed following intravenous isoproterenol injection. Functional sympathetic innervation of the heart does not occur until incubation day 16, and this fact is responsible for the insensitivity to tyramine stimulation on incubation day 5. Although the level of cAMP could not be stimulated above basal level on incubation day 5, beta-antagonists caused a decrease in the level of cAMP, with no decrease in heart rate. These observations indicate that the beta-receptor is coupled to adenylate cyclase on incubation day 5 but it is questionable whether adenylate cyclase is effectively coupled to heart rate. Isoproterenol and tyramine caused a significant elevation in cardiac cAMP and heart rate on incubation day 17 following intravenous in ovo injection. Hearts made sympathetically aneural by removal of premigratory neural crest responded to isoproterenol but not tyramine on incubation day 17 which demonstrates that the morphologically aneural hearts are also functionally aneural.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875191 TI - Acute effects of Soman, Sarin, and Tabun on cyclic nucleotide metabolism in rat striatum. AB - Rats were injected sc with 120 micrograms/kg Soman, 120 micrograms/kg Sarin or 240 micrograms/kg Tabun. At 15 min, 2 h, or 6 h after administration, animals were decapitated along with saline-treated controls, and striatal activities of nucleotide cyclases and phosphodiesterases and striatal cyclic nucleotide levels were determined. All three agents had two similar effects on rat striatal cyclic nucleotide systems: they all increased cyclic GMP levels 15 min after their administration, and they all decreased guanylate cyclase activity 2 h after administration. There were also some different effects elicited by these three organophosphorus compounds. Different effects of Soman and Sarin seem to be mainly due to their different potencies, which in turn influence the time course of their actions. Tabun is quite different from Soman and Sarin in several respects: it rarely causes convulsions at sub-lethal doses, it has no effects on striatal cyclic AMP levels, and it affects enzyme activities 6 h after its administration. These differences may be due to the presence of cyanide instead of fluoride in its structure: i.e., this may be responsible for the different effects of Tabun on striatal cyclic nucleotide systems, and perhaps other biochemical effects. These results also indicate that other neurotransmitter systems, in addition to the cholinergic system, may be involved in organophosphate-induced toxicity. PMID- 2875192 TI - Mechanism of protection by zinc against mercuric chloride toxicity in rats: effects of zinc and mercury on glutathionine metabolism. AB - To investigate the mechanism by which zinc suppresses mercury toxicity, the effects of zinc and mercury on glutathione (GSH) metabolism in the rat kidney were studied. When the time course of GSH level in the rat kidney was examined at 2, 6, and 12 h after treatment of rats with both metals, an increase of GSH was found and was apparently related to the activation of some GSH-associated enzymes. In the kidney of rats treated with both metals, the response of the protective function involving GSH and GSH-associated enzymes depended on the magnitude of mercury toxicity but appeared to be independent of the zinc dosage. The administration of diethyl maleate (DEM), which depletes GSH, increased lipid peroxidation and mercury toxicity concomitantly with a decrease of GSH level in the kidney of rats treated with zinc and mercury. In conclusion, the data suggest that an increased GSH level in the kidney resulting from the activation of GSH associated enzymes plays a role in the protective effect of zinc against mercury toxicity. PMID- 2875193 TI - The hormonal regulation of gene expression of glial markers: glutamine synthetase and glycerol phosphate dehydrogenase in primary cultures of rat brain and in C6 cell line. AB - Increases in the mRNA levels of two neuroglial markers, glutamine synthetase (EC 6.3.1.2; GS) and glycerolphosphate dehydrogenase (EC 1.1.1.8; GPDH), were observed in hydrocortisone-treated cultures of astrocytes and oligodendrocytes, respectively, and in C6 cells by Northern blot analysis and in situ hybridization. In vitro transcription assays demonstrated increased GS transcription in isolated nuclei from hydrocortisone (HC)-treated primary cultures of astrocytes and C6 cells, relative to untreated cells. This increased transcription is reflected in increased GS mRNA levels in the cytoplasm and increased levels of GS protein synthesis. Sodium butyrate (NaB) blocked the glucocorticoid-mediated increase in GS transcription in the primary cultures of astrocytes but not in C6 cells. From our earlier observations (Kumar et al: J Neurochem 43:1455-1463, 1984) we found NaB in combination with HC to increase the levels of GS mRNA and GS protein synthesis (Weingarten et al: FEBS Lett 126:289 291, 1981). We now report that NaB, alone or in combination with HC, does not increase the rate of transcription, suggesting that NaB plays a role in post transcriptional regulation of GS in C6. In addition, we report the presence of two distinct sizes of GS mRNA, 2.9 and 1.8 kb, in the primary cultures of astrocytes and C6 cells. PMID- 2875194 TI - Sequence homology between tyrosine hydroxylase mRNA and a rat adrenal medullary cDNA. AB - A rat adrenal medullary recombinant clone has been isolated by cross hybridization with a tyrosine hydroxylase (TH) cDNA. The new clone has a mRNA size of 5.6 kb and also hybridizes to the 1.9-kb tyrosine hydroxylase message. Southern blot analysis reveals several hybridizing bands in common between the TH cDNA and the adrenal medullary clone. These results demonstrate that the adrenal clone shares sequences in common with the TH gene and/or is closely linked to it in the genome. Hybrid-selected mRNA translation products of the adrenal clone can be immunoprecipitated with dopamine beta hydroxylase antisera. This suggests that the adrenal medullary cDNA may code for another catecholamine pathway enzyme. PMID- 2875195 TI - Management of intra-abdominal aneurysms associated with periarteritis nodosa. AB - Periarteritis nodosa is a disease of small and medium-sized arteries, frequently associated with multiple visceral artery aneurysms. Infrequently, these aneurysms rupture, usually with fatal results. A case of spontaneous rupture of a middle colic artery aneurysm in a patient with periarteritis nodosa is reported, and similar cases in the literature are reviewed. Treatment of a ruptured visceral artery aneurysm requires ligation or resection of the aneurysm without delay. Residual aneurysms are treated with cyclophosphamide and/or prednisone in an attempt to induce regression of the aneurysms. An arteriogram performed after 3 to 4 months of medical therapy determines the need for further surgical intervention. PMID- 2875196 TI - [Evaluation of neuromuscular blocking and circulatory effects of vecuronium bromide and pancuronium bromide by a double blind study]. PMID- 2875198 TI - [Effect of alpha-blocking agent on thyroid function during neuroleptanesthesia in man]. PMID- 2875197 TI - [Rapid tracheal intubation with vecuronium and atracurium]. PMID- 2875199 TI - [Spinal infusion of opiates and somatostatin]. PMID- 2875200 TI - [Alteration of onset of pancuronium and vecuronium by priming principle]. PMID- 2875202 TI - [Type-I HTLV antibody of healthy adults on Okinawa and of Okinawans in Hawaii]. PMID- 2875201 TI - [A case of Sipple's syndrome: importance of the preanesthetic evaluation of the patients by anesthesiologist]. PMID- 2875203 TI - [Adult T-cell leukemia and human T-cell leukemia virus associated diseases in Kochi Prefecture]. PMID- 2875204 TI - [Infection by human T-cell leukemia virus (HTLV-I) by blood transfusion]. PMID- 2875205 TI - Suppressive effect of tritoqualine on lipid peroxidation and enzyme leakage induced by carbon tetrachloride in rat hepatocytes. AB - Since tritoqualine (TRQ) is effective in suppressing the increase of serum transaminases in acute hepatic injured rats induced by some hepatotoxins, protection of the hepatocyte membrane is suggested to be one of the pharmacological effects of TRQ. In the present study, we investigated the effects of TRQ on lipid peroxidation and enzyme leakage caused by carbon tetrachloride (CCl4) exposure in isolated hepatocytes and the liver in vivo, compared with vitamin E. The results were as follows: Hepatocytes isolated from TRQ administered rats showed less enzyme leakage than those from control rats after CCl4 addition. TRQ displayed strong inhibition of lipid peroxidation in isolated hepatocytes. In comparison with vitamin E, TRQ showed almost the same inhibitory action on lipid peroxidation, but a stronger suppression of enzyme leakage. Vitamin E showed a weaker protection from increase of glutamic oxaloacetic transaminase than TRQ, in spite of its stronger inhibition of lipid peroxidation in vivo. From these results, it is suggested that the membrane protecting action of TRQ is partially derived from its suppression of lipid peroxidation, but "another action" may also play an important role in protecting the fragile membrane. PMID- 2875206 TI - [Sites of action of CCK of the guinea pig gallbladder]. AB - Cholecystokinin-octapeptide (CCK-OP) evoked contraction and 3H-acetylcholine (3H ACh) release of the muscle strip of the guinea pig gallbladder were studied. Although hexamethonium (10(-5) M) or tetrodotoxin (10(-6) M) had no effect on CCK OP (10(-8) M) evoked contraction and 3H-ACh release, Ca-free medium almost completely abolished CCK-OP (10(-8) M) evoked 3H-ACh release. In Ca-free medium contraction evoked by CCK-OP (10(-8) M) was reduced to about 84%, which fitted well with the calculated reduction observed in the presence of atropine (10(-6) M). Dibutyryl cyclic GMP (10(-3) M), which significantly reduced CCK-OP (10(-8) M) evoked contraction to about 40%, had no effect on CCK-OP (10(-8) M) evoked 3H ACh release. CCK-OP receptors on the intramural cholinergic neurons might be suggested to be different from those on the muscle cells of the guinea pig gallbladder. PMID- 2875208 TI - Cryptorchidism and testicular cancer. PMID- 2875207 TI - [Clinical and pharmacological studies on alpha-1 antagonists in smooth muscle of human urinary bladder base and prostatic urethra]. PMID- 2875209 TI - [Delegates' meeting and congress 1986. Many things to ponder and to discuss]. PMID- 2875211 TI - [Congress, 7 June 1986: Ethics, a matter of personal conscience]. PMID- 2875210 TI - [Meeting of the delegates, Arbon, 6 June 1986. Congratulations, but also criticisms]. PMID- 2875212 TI - [Nursing research and its limits]. PMID- 2875213 TI - Somatostatin-like peptides alter calcium but not secretin sensitivity of gastrinoma cells. AB - The provocation of gastrin release by calcium or secretin is accepted as a method to differentiate the hypergastrinemia of the Zollinger-Ellison syndrome from that of other causes. We have previously shown that calcium and secretin failed to provoke gastrin release from acutely dispersed gastrinoma cells. This disparity between the in vivo and in vitro effects of these two provocative agents suggests that intermediates may be necessary for calcium- or secretin-induced gastrin release. In an acute cell dispersion, serum-free model, two gastrinomas with low levels of endogenous somatostatin (SRIF) and other peptides failed to respond to calcium or secretin provocation. Conversely, a third tumor containing high levels of endogenous SRIF-like peptides and low levels of other gut peptides did respond to calcium, but not to secretin provocation in vitro. We suggest that in vivo, SRIF modulation of gastrin release is a prerequisite for calcium-simulated gastrin secretion. PMID- 2875214 TI - Antiglucocorticoid steroids have increased agonist activity in those hepatoma cell lines that are more sensitive to glucocorticoids. AB - FU5-5 rat hepatoma (Reuber H35) cells are hypersensitive in that the same percentages of full induction of tyrosine aminotransferase (TAT) occur at much lower concentrations of glucocorticoids than in the related HTC rat hepatoma (Morris) cells. Unexpectedly, these hypersensitive FU5-5 cells also exhibited more agonist activity with the affinity labeling antiglucocorticoids cortisol 21 mesylate and dexamethasone 21-mesylate than did HTC cells (Mercier et al., Endocrinology 112, 601-609 [1983]). In the present study, several other antiglucocorticoids (11-desoxycortisone, progesterone, dexamethasone oxetanone, and RU 486 in addition to dexamethasone 21-mesylate) and the antiandrogen cyproterone acetate were examined to see if chemically unreactive, reversible antisteroids also would exhibit an altered activity (i.e. increased agonist activity) in FU5-5 cells. Each antiglucocorticoid examined did display a 2-fold increased amount of agonist activity in FU5-5 cells, as compared to HTC cells; only RU 486 was predominantly an antagonist in FU5-5 cells but the potency of RU 486 was about 9-fold less than in HTC cells. Dexamethasone, and especially progesterone, was metabolized in FU5-5 and HTC cells. However, differential metabolism in FU5-5 vs HTC cells cannot account for the increased induction of TAT in FU5-5 cells since the amount of agonist activity seen for dexamethasone mesylate (or its metabolites) depended not on the cell type used but rather on the glucocorticoid inducible enzyme monitored, i.e. TAT or glutamine synthetase. The combined data suggest that the hypersensitivity of FU5-5 cells towards glucocorticoid induction of TAT may be linked with the ability of both reversible and irreversible antiglucocorticoids to display increased TAT agonist activity in FU5-5 cells. This behavior was somewhat steroid specific since the antiandrogen cyproterone acetate did not display increased TAT agonist activity in FU5-5 cells compared to HTC cells and was only 2-fold less effective as an antiglucocorticoid in FU5-5. PMID- 2875215 TI - High activity of 17 alpha-oxidoreductase in neonatally grafted mouse testes in adult female mice. AB - Male and female (WB-C57BL/6)F1 hybrid mice were used. Two testes from neonatal mice were grafted into the spleen of adult male and female mice, and the grafted testes were removed 30 and 60 days after grafting. Normal testes from 30- and 60 day old mice were also used. Testicular homogenates were incubated with [14C]4 androstene-3,17-dione or [3H]progesterone, and enzyme activities per g wet tissue and progesterone metabolism were examined. Activity of 17 alpha-oxidoreductase in the grafted testes in females (20 nmol/g/h) was approx. 10 times the activity in the grafted testes in males or in the normal testes, whereas 17 beta oxidoreductase activity in the grafted testes in females was the lowest among these testes. The bilateral ovariectomy performed 1 month before the grafting of neonatal testes, artificial cryptorchidism performed at 20 days of age, and estrogen treatment for 10 days by diethylstilbestrol pellets resulted in no significant changes in 17 alpha-oxidoreductase activities in 30- and 60-day old grafted, cryptorchid or normal testes. The major 17-hydroxy-C19-steroids formed in vitro from progesterone by the grafted testes in female mice were testosterone and 17 alpha-hydroxy-4-androsten-3-one (epitestosterone), but the formation of epitestosterone was insignificant in the normal testes. The present results demonstrate for the first time that epitestosterone is formed as one of major C19 steroids in neonatally grafted mouse testes in females but not in those in males or in normal mouse testes. However, the mechanisms remain unexplained. PMID- 2875216 TI - Anxiolytics and the alcoholic patient. AB - There is a growing appreciation of the heterogeneity of alcoholic patients with implications for treatment intervention. Several recent studies suggest that a minority of alcoholic patients suffer from diagnosable anxiety disorders, although symptoms of anxiety may be present in alcoholics while drinking and in the acute, subacute and protracted periods of abstinence from alcohol. In addition, recent research on biological mechanisms of anxiety may suggest a testable model for examining the existence of an altered biological state associated with symptoms of protracted abstinence in alcoholics, and may suggest an additional rationale for studying newer anxiolytic drugs in the postwithdrawal management of alcoholic patients. In the mid-1970s, Benjamin Kissin made three points regarding the optimal qualities for a tranquilizing drug in the treatment of alcoholism: it should be effective in maintaining individuals in treatment, it should have a low potential for abuse and it should not potentiate the effects of alcohol. Buspirone, a new anxiolytic drug, fulfills the second two criteria. The case for examining anxiolytics with low abuse potential in alcoholic patients is reviewed. PMID- 2875217 TI - [Serotonergic neurons and behavior]. AB - The hypothesis linking decreased serotonin transmission to reduced anxiety as the mechanism in the anxiolytic activity of benzodiazepines conflicts with most clinical observations. Serotonin antagonists show no marked capacity to alleviate anxiety. On the other hand, clinical signs of reduced serotonergic transmission (low 5-HIAA levels in the cerebrospinal fluid) are frequently associated with aggressiveness, suicide attempts and increased anxiety. This brief review attempts to reconcile these human and animal findings by investigating whether anxiety reduction or increased impulsivity are likely to account for animal behavioral changes associated with decreased serotonergic transmission. The effects of manipulating central serotonin on experimental anxiety paradigms in animals (punishment, novelty) are reviewed and compared to the effects of anti anxiety drugs. Anxiety seems neither necessary nor sufficient to induce control by serotonergic neurons on behavior. Further evidence suggests that behavioral effects of anxiolytics thought to be mediated by decreases in anxiety are not caused by the ability of these drugs to reduce serotonin transmission. Blockade of serotonin transmission, especially at the level of the substantia nigra, results in a shift of behavior towards facilitation of responding. This behavioral shift is particularly marked when there is competition between acting and restraining response tendencies and when obstacles prevent the immediate attainment of an anticipated reward. It is proposed that serotonergic neurons are not only involved in behavioral arousal but also in enabling the organism to arrange or tolerate delay before acting. Decreases in serotonin transmission seem to be associated with the increased performance of behaviors which are usually suppressed though not necessarily because of the alleviation of anxiety which might contribute to the suppression. PMID- 2875218 TI - Idazoxan: a novel pharmacological tool for the study of alpha 2-adrenoceptors. AB - The pharmacological properties of idazoxan, 2-[2-(1,4-benzodioxanyl)]-2 imidazoline, were first described four years ago; since then, this compound has been revealed to be one of the most selective alpha 2-adrenoceptor blocking agent presently available. At peripheral sites, idazoxan antagonized the effects of alpha 2 agonists such as azepexole, B-HT 920, M 7, UK 14,304, alpha methylnoradrenaline, clonidine but was ineffective against alpha 1 agonists such as cirazoline and phenylephrine. At presynaptic sites idazoxan increased the tachycardia due to the stimulation of the cardioaccelerator nerve of the dog and antagonized the inhibitory effects of alpha 2 agonists in dogs and rats. As compared to the classical alpha 2-adrenoceptor blocking agents, idazoxan was more selective and as potent as yohimbine, rauwolscine, RS 21361, Wy 26703. At central sites, idazoxan has been found to antagonize the sympathoinhibitory effects of alpha 2 agonists. Therefore, idazoxan is a potent and probably the most selective alpha 2-adrenoceptor blocking agent presently available and is now frequently used for the investigation of peripheral and central alpha 2-adrenoceptors. PMID- 2875219 TI - Comparative study of the effects of stimulation or blockade of beta-adrenoceptors on the head-twitches induced in mice by 5-hydroxytryptophan versus 5-methoxy-N, N dimethyltryptamine. AB - This study aimed at comparing the effects of blockade or stimulation of beta adrenoceptors on the head-twitch response induced in mice by direct (5-MeODMT) or indirect (5-HTP) activation of serotonergic receptors shows that: beta-agonists (clenbuterol and salbutamol) increased the 5-HTP-induced head-twitches and decreased the response to 5-MeODMT. beta-agonists (propranolol and penbutolol) reduced the head-twitches elicited by 5-HTP but enhanced those induced by 5 MeODMT. Under our experimental conditions, desipramine behaved like the beta agonists studied. Prior intracerebroventricular injection of 5,7-DHT enhanced the response to 5-MeODMT but did not prevent the antagonism of clenbuterol against 5 MeODMT-induced head-twitches. These findings suggest that beta-receptors are in a position to regulate differentially serotonin transmission. PMID- 2875220 TI - Classification of benzodiazepine receptor agonists, inverse agonists and antagonists using bicuculline in an in vitro test. AB - The mechanism by which a substance that binds to the benzodiazepine receptor acts as an agonist, an inverse agonist (e.g. methyl-beta-carboline-3-carboxylate (beta CCM] or an antagonist (e.g. Ro 15-1788) was investigated. For this purpose, we studied the influence of bicuculline, an antagonist of gamma-aminobutyric acid (GABA), on the binding of these substances in crude synaptosomal preparation (P2 fraction) containing high levels of endogenous GABA. Displacement curves were performed, using 3H-flunitrazepam in the absence and in the presence of a high concentration (7.10(-5) M) of bicuculline. The ratios of IC50 values with and without bicuculline were significantly higher than 1 for all benzodiazepine agonists investigated (e.g. 1.91 +/- 0.11 (n = 3) for diazepam), about 1 for Ro 15-1788 (0.94 +/- 0.06 (n = 4)) and lower than 1 for beta-CCE (0.55 +/- 0.05 (n = 4)). Statistically significant differences were also observed among benzodiazepine agonists e.g. between flunitrazepam (a sedative-hypnotic drug) and clonazepam (an anticonvulsant drug) or lorazepam (an anxiolytic drug). These data indicate that the ratios of IC50 values with and without bicuculline might provide the basis for an in vitro, pharmacologically relevant, classification of drugs acting on the benzodiazepine receptor. This procedure does not require extensive washing of the membrane preparation, in contrast to the method in which the ratios of IC50 values were determined with and without addition of GABA. PMID- 2875221 TI - [Determination of optimal posology for hypnotic and anxiolytic agents]. PMID- 2875222 TI - A new method for determining co-operativity in neurotransmitter release. AB - It has been accepted for some time that neurotransmitter release exhibits a co operative dependence on calcium. Here we suggest a new procedure for estimating the co-operativity, based on the early rise of synaptic delay histograms of induced release at low quantal content. Measurements of such histograms at the lobster neuromuscular junction are reported. On the basis of this data, and also of data from the literature for other species, a re-examination is made of the conventional hypothesis that the kinetics of release is primarily determined by the time course of entry and removal of calcium ions. Two major new hypotheses for the nature of co-operativity are discussed, both containing the additional feature that membrane depolarization activates a molecule or complex that only then can bind calcium and induce release. The measurements confirm the hypothesis that the co-operativity arises from the action of several complexes between calcium and a depolarization-activated molecule to initiate the release of a vesicle. The co-operativity exponent is estimated to be between three and five in lobster neuromuscular junction and also in crayfish, macrobrachium, and frog. PMID- 2875223 TI - Reperfusion conditions: critical importance of total ventricular decompression during regional reperfusion. AB - This study tests the hypothesis that failure to minimize left ventricular oxygen demands by venting during reperfusion diminishes recovery after controlled blood cardioplegic reperfusion. Of 25 dogs undergoing 2 hours of left anterior descending coronary occlusion, nine were reperfused with normal blood without bypass and five were reperfused with normal blood during total vented bypass. Eleven other dogs were reperfused with aspartate-glutamate-enriched, diltiazem supplemented blood cardioplegic solution for 20 minutes during cardiopulmonary bypass; the left ventricle was decompressed by venting in only five of them. Regional systolic shortening was measured by ultrasonic crystals and myocardial damage estimated from triphenyltetrazolium chloride staining. All segments developed systolic bulging during ischemia (-23% systolic shortening, p less than 0.05), with no segmental recovery after reperfusion with normal blood without bypass (-27% systolic shortening, p less than 0.05) and negligible recovery following reperfusion with normal blood during total vented bypass (6 +/- 2%, p less than 0.05). In contrast, there was immediate recovery of regional contractility (+ 53% systolic shortening, p less than 0.05) in bypassed hearts reperfused with aspartate-glutamate-enriched, diltiazem-supplemented blood cardioplegic solution when venting was used and triphenyltetrazolium chloride nonstaining fell from 43% to 12% (p less than 0.05). Conversely, there was no postischemic recovery (-8% systolic shortening, p less than 0.05) when the same blood cardioplegic reperfusate was given over a comparable time without venting; triphenyltetrazolium chloride damage increased to 25% (p less than 0.05). Minimizing O2 demands by left ventricular decompression with venting during blood cardioplegic reperfusion is essential to ensure immediate functional recovery and limit histochemical damage. PMID- 2875224 TI - Immediate functional recovery after six hours of regional ischemia by careful control of conditions of reperfusion and composition of reperfusate. AB - This study tests the hypothesis that irreversible muscle damage does not occur after as long as 6 hours of ischemia before reperfusion, immediate functional recovery is possible by controlling the conditions of reperfusion during total vented bypass and the composition of the reperfusate with substrate-enriched blood cardioplegic solution, and such control can be accomplished without thoracotomy. Of 43 dogs undergoing 2 to 6 hours of left anterior descending coronary occlusion, seven were studied by ultrastructural and mitochondrial analyses after 6 hours of regional coronary occlusion without reperfusion. Sixteen other dogs were reperfused with normal blood, with the heart in the beating state after 2 to 4 hours of ischemia, and 20 dogs received regional substrate-enriched blood cardioplegic reperfusion after 2 to 6 hours of ischemia for 20 minutes during total vented bypass accomplished through the femoral artery, femoral vein, and transaortic left ventricular venting. Six hours of ischemia without reperfusion caused minimal changes in mitochondrial structure and retained mitochondrial adenosine triphosphate production capacity at 64% of control values despite complete depletion of tissue adenosine triphosphate. Reperfusion with normal blood in the beating, working hearts caused extensive structural damage, reduced reflow, and failed to restore contractility in any instance (-27% systolic shortening, p less than 0.05). In contrast, regional cardioplegic reperfusion during total vented bypass at 2, 4, and 6 hours caused 52 +/- 3%, 41 +/- 7%, and 21 +/- 6% immediate recovery of regional contractile function. The seven hearts reperfused at 6 hours of ischemia had more segmental shortening (21% versus -27%, p less than 0.05), less edema (81% versus 83% water content, p less than 0.05), and more postischemic flow (57 versus 18 ml/100 gm/min in subendocardial muscle, p less than 0.05) than did 2-hour controls, and postischemic ultrastructure was not altered by reperfusion. Six hours of ischemia does not produce irreversible damage, and immediate recovery of contractile function is possible if the conditions of reperfusion are controlled with total vented bypass and a regional substrate-enriched blood cardioplegic solution is administered. Such control can be obtained by the peripheral cannulation technique. PMID- 2875225 TI - Early recovery of regional wall motion in patients following surgical revascularization after eight hours of acute coronary occlusion. AB - This study tests the hypothesis that failure of "successful" streptokinase with and without angioplasty to restore regional wall motion in patients with acute coronary occlusion is due to reperfusion injury that can be avoided in the surgical setting by control of the conditions of reperfusion and the composition of the reperfusate. Of 31 consecutive patients undergoing emergency coronary revascularization, 21 patients were reperfused medically with normal blood (streptokinase with or without angioplasty) following 4.5 +/- 0.4 hours of coronary occlusion in the coronary catheterization laboratory. Surgical reperfusion in 10 patients was with aspartate-glutamate-enriched blood cardioplegic solution during coronary artery bypass grafting after 8.5 +/- 0.5 hours (7.2 to 11.4 hours) of acute coronary occlusion. Hemodynamic instability was present in 5 of 10 surgical patients before operation and resulted from coronary occlusion, whereas 7 to 21 previously stable medical patients became unstable hemodynamically following revascularization with normal blood. Surgical patients evolved fewer electrocardiographically determined infarctions (7/10 versus 21/21, p less than 0.05), had fewer reperfusion ventricular arrhythmias (0/10 versus 9/21, p less than 0.05), had somewhat better global ejection fractions (47% versus 41%), and had shorter hospitalization times (8.3 versus 10.7 days, p less than 0.05); in addition, they all showed significant segmental contractility at discharge (10/10 versus 2/21, p less than 0.05), despite delay of revascularization up to 11 hours. No deaths occurred. These studies imply that acute coronary occlusion is treated best by control of the conditions of reperfusion and the composition of the reperfusate. PMID- 2875226 TI - Tannin is the major agent present in cotton mill dust responsible for human platelet 5-hydroxytryptamine secretion and thromboxane formation. PMID- 2875228 TI - On the localization of Thy-1-like immunoreactivity in the rodent and human nervous system. AB - The neuronal localisation of the surface glycoprotein Thy-1 was studied using the adult mouse iris whole-mount preparation. Polyclonal antibodies to Thy-1 and indirect immunohistochemical techniques were used on fixed tissues. In the adult intact mouse iris a plexus of delicate bundles and fibres was found in both the dilator and sphincter regions. Ovoid negative spots along the bundles were numerous, probably indicating the location of supportive cells. The ciliary body contained strongly immunoreactive bundles oriented in radial and circular patterns. Numerous Thy-1-positive mast cells were found in the irides. All Thy-1 immunoreactive fibres disappeared in intraocular iris transplants after 4 days, leaving only the Thy-1-positive mast cells. A Thy-1-positive fibre plexus reappeared in intraocular iris transplants after 4 weeks, strongly indicating that Thy-1-immunoreactive fibres in adult mouse irides are associated with the nerve fibres and not with their supportive tissue. Distribution of Thy-1-like immunoreactivity in the developing human nervous system is presented for the first time, and its temporal changes are followed from the eighth gestational week to adulthood. At eight weeks the spinal cord and lower brain stem seemed to show virtually no immunoreactivity. At 10 and 31 weeks gestational age immunoreactivity was found preferentially in white matter areas with a granular appearance, becoming more densely aggregated at the later stage. Two months postnatally the internal capsule was strongly positive in an otherwise negative neuropil, only to disappear completely in the adult brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875227 TI - Nonidentical expressions of multiple endocrine neoplasia, type I, in identical twins. AB - We studied 25-year-old HLA- and blood group-identical male twins who had multiple endocrine neoplasia, type I (MEN I). At the time of initial examination, one twin (case 1) had epigastric pain and diarrhea; he was cushingoid in appearance. Further evaluation revealed primary hyperparathyroidism, Zollinger-Ellison syndrome, Cushing's disease, and hyperprolactinemia. Immunostaining of a resected pituitary specimen demonstrated both prolactin and, to a lesser extent, growth hormone reactivity. The nontumorous adenohypophysis showed corticotropic hyperplasia. In contrast, the other twin (case 2) was asymptomatic. He had only primary hyperparathyroidism and hyperprolactinemia. An invasive pituitary adenoma was resected and showed similar proportions of cells with immunoreactive prolactin and those with growth hormone; no nontumorous gland was available for study. Apparently, factors other than heredity may play a role in the expression of MEN I. PMID- 2875229 TI - Metabolism and transport of amino acids studied by immunocytochemistry. AB - The immunocytochemical method for demonstrating amino acids makes it possible to study accumulation and depletion of amino acids in individual tissue compartments resulting from experimental manipulations. We have incubated hippocampal slices in oxygenated Krebs solution, containing various additives, under basal conditions and during synaptic release of transmitters evoked by elevated K+ concentrations or by veratrine. Immunoreactivities for glutamate (Glu-LI), aspartate (Asp-LI), glutamine (Gln-LI), gamma-amino-butyrate (GABA-LI) and taurine (Tau-LI) have been demonstrated by specific antibodies after fixation of the slices in glutaraldehyde. Prolonged depolarisation depleted Glu-LI, Asp-LI and Gln-LI from nerve-ending-like structures. GABA-LI was less affected and Tau LI not affected at all. The depletion of immunoreactivities could be prevented by metabolic precursors of transmitter amino acids, notably glutamine. This effect of glutamine was abolished by inhibiting glutaminase with diazooxonorleucine. Glu LI, Asp-LI, GABA-LI and Gln-LI accumulated in astroglial cells during conditions of prolonged depolarization-induced release. The accumulation of GABA-LI in glia was strongly increased by inhibition of aminotransferases by aminooxyacetic acid. The described changes in Glu-LI were prevented by low Ca2+/high Mg2+, and promoted when the glial enzyme glutamine synthetase was inhibited by methionine sulfoximine. D-Aspartate, a metabolically inert competitive inhibitor/substrate for high affinity uptake of glutamate, inhibited the accumulation of Glu-LI in glia. The results confirm the biochemically derived theories on metabolic compartmentation in nervous tissue, and add knowledge on the dynamics of the cellular distribution of amino acids. They also indicate the possibilities offered by the present approach for studying metabolism and pharmacology at the cellular level. PMID- 2875230 TI - Evaluation of the immunocytochemical method for amino acids. AB - Free amino acids can be coupled to proteins by glutaraldehyde. Rabbits immunised with a bovine serum albumin-glutaraldehyde-amino acid conjugate form antibodies that recognise similar conjugates with brain proteins in glutaraldehyde-fixed tissue. Antisera raised against conjugated GABA (gamma-aminobutyrate), glutamate, aspartate, taurine, glutamine, or glycine were tested against a variety of small molecular compounds that had been fixed by glutaraldehyde to brain protein and immobilised on cellulose ester filters for processing together with the brain sections. This system permitted closely similar conditions for testing and immunocytochemistry. After removing antibodies against the carrier used for immunisation and against cross reacting amino acid conjugates the antisera showed a high specificity. The specific nature of the antisera was corroborated by solid phase adsorption to the homologous antigens and by inhibition experiments with free amino acids and amino acid-glutaraldehyde fixation complexes. After transection of the striatonigral pathway the ipsilateral substantia nigra was almost depleted of GABA-like immunoreactivity; this observation lends additional support to the selectivity of the GABA antiserum. A semiquantitative relation was established between the concentration of amino acid before fixation in a model system and the subsequent intensity of immunostaining. Similar model experiments suggested that the conjugation of an amino acid to brain protein with glutaraldehyde, and the immunoreactivity of the conjugates, may be significantly inhibited in the presence of high concentrations of other amino compounds. PMID- 2875231 TI - Immunocytochemical studies on axonal transport in adrenergic and cholinergic nerves using cytofluorimetric scanning. AB - The axonal transport of adrenergic and cholinergic axonal organelles in rat sciatic nerve has been studied using a cytofluorimetric scanning (CFS) technique. This technique gives quantitative data on material which accumulates in a nerve relative to a crush, as well as morphological and morphometrical information about the accumulated axons in the nerve. One important advantage is that several substances can be measured in the same nerve segment, thus reducing the number of animals needed. The substances must be made fluorescent, and in this study we have investigated noradrenaline (NA), using formaldehyde induced fluorescence, and dopamine beta-hydroxylase (DBH), tyrosine hydroxylase (TH), neuropeptide Y (NPY) and two cholinergic vesicle components (a transmembrane glycoprotein and synapsin I) using indirect immunofluorescence. The antisera used for labelling immunoreactive material (IR) were produced in rabbit or goat (DBH). In adrenergic axons NA, DBH-IR and TH-IR accumulated with time after crushing the nerve as described earlier with biochemical techniques. After reserpine, the amounts of amine granules transported distally in the sciatic nerve initially fell, but recovered during day 2 after reserpine. At day 4 the amount of NA and DBH-IR which was transported distally in the axons was supranormal, 160% and 140% of control, respectively, but the level of NPY-IR was not increased, even falling to subnormal at day 4, indicating different mechanisms for regulating the synthesis of DBH and NPY which are suggested to co-exist in axonal adrenergic large dense core vesicles. In cholinergic motor axons organelles, recognized by rabbit-anti cholinergic synaptic vesicles-antiserum (RASVA) and by anti-synapsin I-antiserum, are transported distally at a rapid rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875232 TI - Transmitters and modulators in the superior cervical ganglion of the rat. AB - Several transmitters and modulators have been found to exist in the superior cervical ganglion of the rat. It has been shown that noradrenaline is present in the principal neurons and dopamine is the main catecholamine in the small intensely fluorescent cells. 5-hydroxytryptamine and histamine have been investigated immunohistochemically and found to be present only in the small intensely fluorescent cells of an adult rat, in the same cells which are also immunoreactive to tyrosine hydroxylase. On the other hand, enkephalins which were studied using highly specific antibodies against methionine-enkephalin-arginine phenylalanine and methionine-enkephalin-arginine-glycine-leucine were found in the principal neurons and nerve fibres. Ligation studies showed that enkephalins in the superior cervical ganglion of the rat are both of intrinsic and extrinsic origin. It is evident that the transmission in the sympathetic ganglion is complex. The possible function of the transmitter and modulator candidates is discussed. PMID- 2875233 TI - Localization and possible function of polyamines in protein and peptide secreting cells. AB - Three different cytochemical methods, the formaldehyde-fluorescamine and the ortho-phtalaldehyde fluorescence cytochemical methods as well as immunocytochemistry have been developed for localising the polyamines spermidine and spermine in tissue. All three methods produce identical results and show polyamines to occur inter alia in high concentrations in certain protein- and peptide-secreting cells. Many of these cells also show the capacity to metabolise monoamines and belong to the amine content or amine precursor uptake and decarboxylation (APUD) series. In cell types where fluorescence microscopical resolution allows, most polyamines appear to be localised to secretory granules. Moreover, studies on isolated pancreatic islets reveal active and glucose dependent polyamine biosynthesis to occur in insulin cells. Possible function of polyamines in secretory granules are discussed in the light of the above findings. PMID- 2875234 TI - Effects of SK&F 93944 (Temelastine), a potent histamine H1-receptor antagonist in pharmacologic and antigen-induced bronchoconstriction. AB - SK&F 93944, a previously reported non-sedating histamine H1-receptor antagonist, was evaluated for its ability to block pharmacologic-and antigen-induced bronchoconstriction. In the isolated guinea pig trachea, SK&F 93944 (10(-9)-10( 7) M) produced a concentration-dependent inhibition of contractions produced by histamine (pKB = 9.5). Another histamine antagonist, mepyramine (10(-8)-10(-6) M), was less potent (pKB = 8.5). SK&F 93944 (10(-8), 10(-7) M) also significantly depressed the rapid initial phase of antigen-induced contraction of the guinea pig trachea from animals actively sensitized to ovalbumin, while having no effect on the later, more protracted phase of the contractile response. In anesthetized mongrel dogs, selective inhibition of histamine (20 micrograms/kg, i.v.)-induced bronchoconstriction was achieved by SK&F 93944 in doses as low as 30 micrograms/kg, i.v. Terfenadine, a purportedly selective histamine H1-receptor antagonist, blocked both histamine and acetylcholine-induced bronchoconstriction at doses similar to SK&F 93944. In mongrel dogs natively allergic to Ascaris suum antigen, pretreatment with aerosols of either SK&F 93944 or mepyramine (1%; 50 tidal breaths) significantly inhibited bronchospasm elicited by increasing aerosol concentrations of antigen. Thus, SK&F 93944 is a highly potent, selective histamine H1-receptor antagonist which is efficacious vs. pharmacologic and antigen-induced bronchoconstriction. PMID- 2875235 TI - Effect of changing levels of physical activity on blood-pressure and haemodynamics in essential hypertension. AB - The long-term effect of exercise on blood-pressure (BP) was assessed in 13 untreated patients with essential hypertension. After a 6-week run-in period the levels of activity studied were sedentary, 45 min bicycling at 60-70% of maximum work capacity (Wmax) three times per week (3/week), and 45 min bicycling seven times per week (7/week), each for 4 weeks. The order differed between subjects in accordance with a Latin square. Supine BP, 48 h after each phase, averaged 148/99 mm Hg in the run-in and 143/96 mm Hg in the sedentary phase; it fell below values in the sedentary phase by 11/9 mm Hg with 3/week exercise, and by 16/11 mm Hg with 7/week exercise (both p less than 0.01). With increasing activity total peripheral resistance fell and the cardiac index rose. Plasma noradrenaline concentration fell below values in the sedentary phase by 21% and 33% after 3/week and 7/week exercise. Bodyweight and 24 h sodium excretion remained constant. Moderate regular exercise lowers BP and seems to be an important non pharmacological method of treating hypertension. PMID- 2875236 TI - Cyclosporin in therapeutic doses increases renal allograft vascular resistance. AB - In fourteen renal transplant patients converted from cyclosporin to azathioprine for financial reasons renal blood flow was greater and renal vascular resistance lower after conversion. These changes occurred without any change in serum creatinine. This finding suggests that the renal allograft vasoconstriction induced by cyclosporin occurs before evidence of nephrotoxicity and that the vasoconstriction is reversible. Renal allograft recipients had cyclosporin induced haemodynamic changes even early (2 weeks) after transplantation, when the allograft is still denervated. These findings may explain the increased sensitivity to other nephrotoxic agents and hypertension observed in cyclosporin treated patients. PMID- 2875237 TI - Streptococci as urinary pathogens. AB - In a 2-month prospective study of streptococci isolated from urine specimens in the laboratory, 242 strains of catalase-negative gram-positive cocci or coccobacilli were isolated in substantial numbers from 11,725 specimens. These comprised 10% of the important isolates. Species identification of all isolates was undertaken. 74 (30%) of the isolates were of species other than Streptococcus faecalis and S agalactiae. 79 (33%) were not detected on cysteine-lactose electrolyte-deficient agar after overnight incubation in a carbon dioxide incubator. 20 of the 24 isolates of coccobacilli were Gardnerella vaginalis. Many of the isolates of fastidious species were accompanied by pyuria. An isolation protocol practicable in busy laboratories is proposed. PMID- 2875238 TI - Transmission of chronic idiopathic vitritis in mice by inoculation of human vitreous containing leucocyte phagolysosomal bacteria-like bodies. AB - Vitreous humour from chronic idiopathic vitritis (CIV) patients containing 0.5 0.7 micron diameter bacteria-like bodies (BLB) in polymorphonuclear leucocytes was inoculated into the eyelids of 100 mice. 200 control mice received either eye bank vitreous or saline. After 12 months, 53 mice that received CIV vitreous, but none of the controls, had clinical signs of ocular inflammation (p less than 0.05); 15 of the mice that received CIV vitreous and none of the controls had histological evidence of chronic deep ocular inflammation, including vitritis (p less than 0.05); 95 CIV-vitreous-inoculated and 38 control mice were dead (p less than 0.05); and 3/3 of the CIV-vitreous group, compared with 0/3 controls, that were killed for histological assessment had phagolysosomal BLB identical to those in the CIV-vitreous inocula. The findings indicate that the BLB are pathogenic for mice. PMID- 2875239 TI - Evaluation of six enzyme immunoassays for antibody against human immunodeficiency virus. AB - Six commercial enzyme immunoassays (EIA) were evaluated in 6488 serum samples, with immunoblot analysis as the confirmatory test for antibodies against human immunodeficiency virus (HIV). The Abbott and Wellcome tests identified all 163 immunoblot-positive samples correctly, whereas the other tests did not detect 1-3 samples. In AIDS patients (predominantly with antibodies to gp41env) Organon's EIA was less sensitive (p less than 0.05) and Wellcome's more sensitive (p less than 0.05) than the immunoblot assay. In symptom-free anti-HIV-positive subjects (antibodies to almost all viral antigens and high titres of anti-p24gag) all the EIA were significantly (p less than 0.05) less sensitive than the immunoblot assay. The frequencies of false-positive reactions in a "tricky" panel of samples from patients with autoimmune and acute viral diseases and in a blood-donor panel were Abbott 9.5%, 0.42%: Organon 1.7%, 0%; Litton 1.0%, 0.4%; Behring 2.7%, 0.06%; Wellcome 0%, 0%; and Pasteur 0%, 0.02%. The results of a seventh EIA (Dupont) were excluded from the study at the company's request. All six EIA evaluated are suitable tests for anti-HIV screening in samples from patients and blood donors. PMID- 2875240 TI - Is chronic renal transplant rejection a non-immunological phenomenon? AB - Five patients with chronic renal transplant rejection were subjected to dietary protein restriction (0.6 g/kg ideal body weight daily) with no change in immunosuppressive therapy. In all five patients the slope of the curve of reciprocal serum creatinine and time decreased (mean -46.0 +/- 11.8 before diet fell to -11.7 +/- 9.4; p less than 0.01). These findings support the hypothesis that non-immune mechanisms are dominant is chronic renal transplant failure. PMID- 2875242 TI - Jet lag and its pharmacology. PMID- 2875241 TI - Intracellular surveillance of persisting viral infections. Human genital cancer results from deficient cellular control of papillomavirus gene expression. AB - A model is proposed to explain basic features of viral oncogenesis in man such as the long interval between primary infection and tumour appearance, the small number of infected individuals in whom cancer develops, and the monoclonality of the tumours. These cancers are viewed as the result of failing intracellular control of persisting viral genomes in proliferating cells. This type of intracellular surveillance is regarded as a defence mechanism ancestrally older than immunological control, protecting the host at cellular level against potentially lethal effects of coevolving persisting viruses. PMID- 2875243 TI - Home, hospital, or birthroom? PMID- 2875244 TI - Molecular genetics and osteogenesis imperfecta. PMID- 2875245 TI - Orbital cellulitis. PMID- 2875246 TI - Ureteroscopy. PMID- 2875247 TI - Protective efficacy of BCG against leprosy in Northern Malawi. AB - The effectiveness of a BCG vaccination programme in protecting against leprosy was assessed by case-control and cohort analyses of data from the Lepra Evaluation Project in Karonga District, Northern Malawi. Results indicate that BCG provides at least 50% protection against leprosy in this population and that protection is independent of age, sex, schooling status, or location within the project area. Agreement between these findings and those from a controlled trial in Uganda indicates that BCG is sufficiently effective against leprosy in East and Central Africa to be considered an important element of leprosy control in that region. PMID- 2875249 TI - Manic-depressive illness. PMID- 2875248 TI - Risk of carcinoma following gastric operations for benign disease. A historical cohort study of 3470 patients. AB - The risk of stomach cancer was analysed in a cohort of 3470 patients who had had gastric surgery for benign disease between 1900 and 1969. In 87 patients (2.2%) stomach-stump cancer was diagnosed in the follow-up period 1970-84. By comparison with the total incidence of stomach cancer in the same region during the same time period, the observed versus expected ratio in the post-surgery group was 2.1 (p less than 0.001) and did not differ between men and women. At 5-10 years postoperative the risk of cancer was no different from that in the total population, whereas after 40-45 years it was 7.3-fold higher. The risk was unrelated to primary diagnosis or type of operation. PMID- 2875250 TI - Chernobyl. PMID- 2875251 TI - Depression and prostacyclin infusion. PMID- 2875252 TI - Intralesional injection of 15(S)-hydroxyeicosatetraenoic acid in psoriasis. PMID- 2875253 TI - Psychiatric side-effects of high-dose lisuride therapy in parkinsonism. PMID- 2875254 TI - Cerebrospinal fluid inflammation during OKT3 therapy. PMID- 2875255 TI - Fatal liver failure in children on valproate. PMID- 2875256 TI - Staphylococcal endocarditis after dental extraction. PMID- 2875257 TI - Abnormal ocular motility as early sign of CNS involvement in HIV infection. PMID- 2875258 TI - False-positive results with HIV ELISA kits. PMID- 2875259 TI - Fast neutron therapy. PMID- 2875260 TI - Should lesbians give blood? PMID- 2875261 TI - Waterborne giardiasis in the United States 1965-84. PMID- 2875262 TI - Intrauterine and ectopic pregnancy after in-vitro fertilisation. PMID- 2875263 TI - Human rabies vaccines induce neutralising antibodies against the European bat rabies virus (Duvenhage) PMID- 2875264 TI - Alcohol and haemorrhagic stroke. PMID- 2875265 TI - Eradication by alpha-interferon of one clone in biclonal hairy cell leukaemia. PMID- 2875266 TI - Mortality and social inequalities. PMID- 2875268 TI - Replication of clinical trials. PMID- 2875267 TI - Persecution of doctors in Iran. PMID- 2875269 TI - Maternal smoking during pregnancy and the risk of childhood cancer. PMID- 2875270 TI - Preparation of fine needle aspirates for immunocytochemical studies. PMID- 2875271 TI - Effect of high tonic levels of luteinising hormone on outcome of in-vitro fertilisation. PMID- 2875272 TI - Detection of regional myocardial ischaemia by NADH laser fluorimetry during human left heart catheterisation. PMID- 2875273 TI - Exacerbation of eczema by formalin-containing hepatitis B vaccine in formaldehyde allergic patient. PMID- 2875274 TI - Diltiazem and economic use of cyclosporin. PMID- 2875275 TI - Hepatitis B protection of endoscopy staff. PMID- 2875276 TI - Childhood leukaemia in the West of Scotland. PMID- 2875277 TI - Soft tissue sarcomas in Seveso. PMID- 2875278 TI - Hypolipidaemia in fire-eaters. PMID- 2875279 TI - Praziquantel in treatment of cerebral schistosomiasis. AB - The effectiveness of standard single-day praziquantel treatment (60 mg/kg) was prospectively evaluated in nine patients with seizures caused by cerebral Schistosoma japonicum infection. Eight patients were cured when discharged from the study, an average of 6 months after receiving praziquantel. They were seizure free in the absence of anticonvulsants, their electroencephalograms were normal, and no major abnormalities could be detected on neurological examination. Serial computed tomography scanning revealed rapid dissipation of cerebral oedema and complete or near-complete resolution of mass lesions. No serious adverse effects of praziquantel were encountered. The ninth patient was not cured but improved greatly in the months after treatment. Thus, single-day treatment with praziquantel is safe and effective in cerebral schistosomiasis. PMID- 2875280 TI - Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. AB - The Northwick Park Heart Study (NPHS) has investigated the thrombotic component of ischaemic heart disease (IHD) by the inclusion of measures of haemostatic function. Among 1511 white men aged between 40 and 64 at the time of recruitment, 109 subsequently experienced first major events of IHD. High levels of factor VII coagulant activity and of plasma fibrinogen were associated with increased risk, especially for events occurring within 5 years of recruitment. These associations seemed to be stronger than for cholesterol, elevations of one standard deviation in factor VII activity, fibrinogen, and cholesterol being associated with increases in the risk of an episode of IHD within 5 years of 62%, 84%, and 43% respectively. Multiple regression analyses indicated independent associations between each of the clotting factor measures and IHD but not between the blood cholesterol level and IHD incidence. The risk of IHD in those with high fibrinogen levels was greater in younger than in older men. Much of the association between smoking and IHD may be mediated through the plasma fibrinogen level. The biochemical disturbance leading to IHD may lie at least as much in the coagulation system as in the metabolism of cholesterol. PMID- 2875281 TI - Fulminant hepatitis B in successive female sexual partners of two anti-HBe positive males. AB - In two separate families, consecutive, unrelated female sexual partners of a symptom-free, male, HBsAg-positive carrier died of fulminant hepatitis B. Although one man was HBeAg positive on the first occasion, both men were considered of low infectivity, being anti-HBe positive, negative for serum DNA polymerase activity, and negative for serum hepatitis B virus (HBV) DNA when their second partners presented with fulminant hepatitis B. By means of molecular hybridisation techniques, both men were found to have HBV DNA (3.2 kb) in seminal fluid, sputum, saliva, peripheral blood leucocytes, and liver. PMID- 2875282 TI - The corticotropin-releasing-hormone test versus the high-dose dexamethasone test in the differential diagnosis of Cushing's syndrome. AB - The diagnostic accuracy of the corticotropin-releasing-hormone (CRH) test was compared with that of the oral high-dose dexamethasone suppression test in the differential diagnosis of Cushing's syndrome. A false-negative response to CRH was present in 9% (2 of 22) of patients with pituitary-dependent Cushing's disease and to high-dose dexamethasone in 11% (2 of 18). All 3 patients with Cushing's syndrome due to an adrenal adenoma were unresponsive to both CRH and dexamethasone. The only patient with ectopic corticotropin secretion had a false positive response of corticotropin to dexamethasone and no response of corticotropin to CRH. Simultaneous failure of both tests to indicate the cause of Cushing's syndrome did not occur in this series, except in 1 patient with Cushing's disease and overt macronodular hyperplasia. It is concluded that the diagnostic accuracy of the CRH test in patients with Cushing's syndrome is comparable to that of the high-dose dexamethasone test and that the highest discriminatory score in the differential diagnosis of Cushing's syndrome is achieved by using both a CRH test and a high-dose dexamethasone test. PMID- 2875284 TI - Tethered spinal cord. PMID- 2875283 TI - Knee moments in Duchenne muscular dystrophy. AB - The gait of 7 boys with Duchenne muscular dystrophy (DMD) who could walk unaided and 21 normal boys was analysed by means of a video recording technique linked to a Kistler force plate. An electronic device was used to superimpose the patient's ground reaction vector on the video recording of their walking. This recording was analysed to obtain sequential values for the moments developed around the knee during the walking cycle. The equinus gait of boys with DMD is shown to be a necessary adaptation to keep the forces about proximal joints, particularly the knee, within limits controllable by weakened muscles. These findings explain the observation that elongation of the Achilles tendon to correct contracture at the ankle can have irrevocably damaging effects on gait. PMID- 2875285 TI - Depression and Cushing's syndrome. PMID- 2875286 TI - Meningococcal infections. PMID- 2875287 TI - Sex, hormones, and atherosclerosis. PMID- 2875288 TI - The depth of anaesthesia. PMID- 2875289 TI - Loa loa--a pathogenic parasite. PMID- 2875290 TI - Meningococcal serotypes and serogroup B disease in north-west Europe. AB - Examination of the trends of meningococcal infection in Norway, Iceland, Faroe Islands, Denmark, England and Wales, and the Netherlands, has shown that Neisseria meningitidis B:2b:P1.2 and/or B:2a:P1.2 phenotypes were associated with peaks of infection in the Netherlands in 1966, in Iceland 1976-77, and in England and Wales in 1973-75. These strains were present in all six countries in the decade 1970-80 but their prevalence is now practically negligible. In contrast the prevalence of the B:15:P1.16 phenotype has risen. In the Faroe Islands and northern Norway this change in serotype prevalence has been followed by rises in incidence of meningococcal disease; the same is happening in England and Wales but not yet in the other countries. PMID- 2875291 TI - An outbreak of meningococcal disease in Gloucestershire. AB - Between October, 1981, and March, 1986, there were 65 cases of meningococcal infection, about five times the expected number, in Gloucester Health District. The cases, mainly in teenagers and young adults, were clustered in the Stroud district and in the southern part of Gloucester City, and most were caused by a sulphonamide-resistant group B type 15 meningococcus. 2 patients died. Only 57% of meningitis cases were formally notified. 7 (11%) patients had septicaemia without meningitis, not a notifiable disease. All meningococcal disease should be made notifiable and meningococci should be serotyped routinely so that the epidemiology of the disease can be monitored before the introduction of suitable vaccines. PMID- 2875292 TI - National Institutes of Health awards to institutions in foreign countries, 1976 85. AB - Foreign institutions are eligible for grants from the US National Institutes of Health (NIH) for biomedical research. Applications undergo a two-tier process of peer review. Most applications are approved and about a third succeed in obtaining funding. Each year the NIH awards about 300 research grants and contracts to foreign institutions and supports another 100 international research fellows. In the fiscal year 1984, the NIH spent about +35 million on these awards -about half the amount that it spent on international activities. PMID- 2875293 TI - Management of type I diabetes with ciamexone. PMID- 2875294 TI - Distribution of meningococcal meningitis in England and Wales 1982-86. PMID- 2875295 TI - Cyclosporin and graft survival. PMID- 2875296 TI - Cryopreservation does not affect future of human fertilised eggs. PMID- 2875297 TI - Indomethacin in the relief of AIDS symptoms. PMID- 2875298 TI - HIV IgM antibodies in risk groups who are seronegative on ELISA testing. PMID- 2875299 TI - Half-life and in-vivo recovery of heated factor VIII concentrates. PMID- 2875300 TI - Frequency of XbaI polymorphism in myocardial infarct survivors. PMID- 2875301 TI - Torsade de pointes with prenylamine: do we still need the drug? PMID- 2875302 TI - Neural tube defects and sex ratio. PMID- 2875303 TI - Regression of liver metastases in patient with gastrin-secreting tumour treated with SMS 201-995. PMID- 2875304 TI - Exacerbation of asthma after nebulised beclomethasone diproprionate. PMID- 2875305 TI - First-aid for burns. PMID- 2875306 TI - Multiple sclerosis and Borrelia burgdorferi. PMID- 2875307 TI - Health visitors and the elderly. PMID- 2875308 TI - Fenoprofen and free triiodothyronine assays. PMID- 2875309 TI - Dopamine D2 receptors and SCH 23390 treatment. PMID- 2875310 TI - Electric shocks for snakebite. PMID- 2875311 TI - Prospects for antibody-targeted radiotherapy of cancer. PMID- 2875312 TI - Hormone release by electroconvulsive therapy. PMID- 2875313 TI - Percutaneous laser recanalisation of coronary arteries. PMID- 2875315 TI - Rubbers, water, and legionella. PMID- 2875314 TI - Epicardial monophasic action potentials. PMID- 2875316 TI - Perforation of heart during attempt to drain pleural cavity. PMID- 2875317 TI - Efficacy of antihypertensive drug treatment according to age, sex, blood pressure, and previous cardiovascular disease in patients over the age of 60. AB - Results of the European Working Party on High Blood Pressure in the Elderly (EWPHE) trial have been analysed in relation to age, sex, blood pressure, and previous cardiovascular disease. Cardiovascular mortality and the cardiovascular study-terminating events were significantly and independently related to treatment, age, cardiovascular complications at randomisation, and systolic but not diastolic blood pressure. The benefits of treatment observed in the trial seemed to be independent of entry blood pressure and the presence or absence of cardiovascular complications at entry. There was some evidence that treatment effect decreases with advancing age. Little or no benefit from treatment could be demonstrated in patients over the age of 80 years, the great majority of whom were women. PMID- 2875318 TI - Genetic control of low-density-lipoprotein subclasses. AB - In a study of lipoprotein subclasses in 79 healthy members of sixteen nuclear families evidence was obtained that low-density-lipoprotein (LDL) subclass patterns determined by gradient-gel electrophoresis are influenced by a common allele at a single genetic locus. The estimated frequency of the allele leading to the phenotype characterised by predominance of small, dense LDL subclasses was about 15%. Expression of this phenotype appears to be age dependent, in that most affected subjects in this population were older than 40 years. Although plasma lipid levels were normal in most subjects with this trait, levels of plasma apoprotein B and triglyceride were higher and levels of apoprotein AI and HDL2 lower than in unaffected family members. It is possible that this genetic trait may interact with other genetic or environmental variables in predisposing affected individuals to atherogenic lipoprotein and apoprotein profiles. PMID- 2875319 TI - Atherogenicity of blood serum from patients with coronary heart disease. AB - The sera from 62 of 68 patients with coronary heart disease (CHD) caused a two to five fold elevation in the intracellular cholesterol in primary cultures of subendothelial cells derived from grossly normal intima of human aorta. The sera from 33 of 42 healthy subjects did not show atherogenic properties in culture. Atherogenic potential correlated directly with the serum apolipoprotein-B apolipoprotein A1 ratio, but not with the level of total cholesterol, high density-lipoprotein cholesterol, apo-B, or apo-A1. The sera from patients with CHD also facilitated deposition of lipids in the medial smooth muscle cells of human aorta and mononuclear blood cells, though to a lesser degree. They had no such effect on endothelial cells of human aorta and umbilical vein, or human embryo fibroblasts. PMID- 2875321 TI - Treatment of autonomic neuropathy with a somatostatin analogue SMS-201-995. AB - Eight patients with postprandial hypotension and orthostatic hypotension were treated with the somatostatin analogue SMS-201-995. Low doses of this drug (0.2 0.4 microgram/kg) raised the blood pressure after breakfast in all six patients with postprandial hypotension. 60 min after breakfast the mean sitting blood pressure was 35 +/- 10 (SEM) mm Hg higher after administration of SMS-201-995 0.4 microgram/kg than after placebo (p less than 0.001). Larger doses (up to 1.6 micrograms/kg) raised upright blood pressure during the postprandial period in five of seven patients. Before therapy three patients were unable to stand after eating; after an injection of SMS-201-995 0.8 microgram/kg at the beginning of breakfast they were able to walk for 35-100 min. The duration of therapeutic effect of each injection was 3-6 h. Treatment was followed by abdominal cramps and nausea in two patients with gastroparesis diabeticorum. SMS-201-995 holds promise as a treatment for postprandial hypotension and orthostatic hypotension. PMID- 2875320 TI - Transmissibility of human immunodeficiency virus in haemophilic and non haemophilic children living in a private school in France. AB - In a study of the transmissibility of human immunodeficiency virus (HIV) in haemophilic and non-haemophilic children living together in a boarding school in France, half of the haemophilic children had seroconverted by the end of a 3-year study period. By contrast none of the non-haemophilic children seroconverted. All children had had close casual contact, some of them for several years. Hepatitis B virus (HBV) markers detected in all polytransfused haemophiliacs were found in 4 of 20 control children in the school, whereas all healthy youngsters living with their families were HBV negative. This study adds support to the theory that transmissibility of HIV among casual contacts is low and that there is no reason to exclude HIV-antibody carriers from communities. PMID- 2875323 TI - The occupational mortality supplement: why the fuss? PMID- 2875322 TI - Living with radiation--after Chernobyl. PMID- 2875324 TI - "Looks like SVT". PMID- 2875325 TI - Care of disabled--a cacophony. PMID- 2875326 TI - Familial moles and malignant melanoma in The Netherlands. PMID- 2875327 TI - Children in Juba, southern Sudan: the second and third years of life. AB - A prospective study of child health has been continued until the children were 36 months old. The mortality rate in the second year was 8.1%. The most common cause of death was chronic undernutrition. The 79 children suffered seventy-six episodes of faltering weight gain; 47 lost 0.5 kg, and most did not reach their former weight for 5 months. Marasmus complicated eighteen faltering episodes; three were fatal. Of 45 children remaining in Juba to their 36th month none had marasmus, and their health was improved. 15 of 53 children, mean age 2.25 years, showed developmental delay. After 10 months 7 showed continued delay. Hepatitis B seemed to be transmitted to the children from both mothers and other sources. Day care centres can help chronically undernourished children, and health education should be directed towards the parents' capabilities. PMID- 2875328 TI - Simulated cardiac arrests for monitoring quality of in-hospital resuscitation. AB - To improve monitoring of the quality of resuscitation after cardiac arrest staff performance in 47 simulated cardiac arrests was assessed. The exercise revealed many unsuspected deficiencies. Nurses did not apply mouth-to-mouth resuscitation, use the hand-held defibrillator, or give supplementary oxygen while awaiting the arrival of the arrest team; the availability of different models of defibrillators led to confusion and delay in defibrillation; suction equipment did not suck hard enough; lack of special protocols for areas such as paediatrics led to medication errors. Remedial measures included in-service education for nurses, purchase of new defibrillators and portable suction machines, and preparation of detailed protocols for paediatric, haemodialysis, and obstetric units. The use of mock arrests helps in the immediate and definitive identification of deficiencies in the quality of cardiac resuscitation. Furthermore information obtained by the use of mock arrests spurs physicians and hospital administrators to correct the deficiencies promptly. PMID- 2875330 TI - Medicine in turbulent times. PMID- 2875329 TI - Self-prescribing by way of pharmacies in three Asian developing countries. AB - The pattern of advice given and drugs dispensed at 75 Asian pharmacies in response to the presentation of a fictitious infant with diarrhoea were studied. Only 16 of the 75 pharmacies gave the appropriate advice--oral rehydration or consultation with a health worker. 19 of 25 pharmacies in Bangladesh, 16 of 25 in Sri Lanka, and 24 of 25 in Yemen Arab Republic dispensed drugs, with or without oral rehydration solution. Fixed-dose combinations of antibiotics and antidiarrhoeal drugs were common. The results are discussed in relation to national drug and diarrhoeal control policies. After further development of the method it might become a useful monitoring instrument. PMID- 2875331 TI - Meningococcal bacteraemia in febrile contacts of patients with meningococcal disease. PMID- 2875332 TI - Intact smallpox virus particles in an Italian mummy of sixteenth century. PMID- 2875333 TI - Sodium and water depletion in ileostomy patients. PMID- 2875334 TI - Campylobacter pyloridis, urease, and gastric ulcers. PMID- 2875335 TI - Treatment of enterocutaneous fistulas with somatostatin. PMID- 2875336 TI - Anti-Rh(D) immunoglobulin for AIDS-related thrombocytopenia. PMID- 2875337 TI - Unusual intrafamilial transmission of human immunodeficiency virus. PMID- 2875339 TI - Patient-triggered ventilation in the newborn. PMID- 2875338 TI - False-positive immunoblot results with antibodies against human immunodeficiency virus. PMID- 2875340 TI - Beta-cell function in type II diabetes. PMID- 2875342 TI - False-negative finding on chorionic villus sampling. PMID- 2875341 TI - Epirubicin-induced primary Sjogren's syndrome. PMID- 2875343 TI - Persistent Coxsackie B infections in immunocompetent patients. PMID- 2875344 TI - Fatal poisoning and membrane stabilising activity. PMID- 2875345 TI - Panic attacks and excessive aspartame ingestion. PMID- 2875346 TI - From Nazi holocaust to nuclear holocaust. PMID- 2875347 TI - Inequality, poverty, and health. PMID- 2875348 TI - Effects of animal research on life expectancy. PMID- 2875349 TI - Obstetrics and gynaecology at the London Hospital. PMID- 2875350 TI - Mental handicap with psychiatric illness. PMID- 2875351 TI - Monoclonal antibody to detect Pneumocystis carinii. PMID- 2875352 TI - Thiazide-induced dilutional hyponatraemia masquerading as subarachnoid haemorrhage. PMID- 2875354 TI - Red-cell surface charge in glomerular disease. PMID- 2875353 TI - Kidney transplant regraft results improved by peroperative blood transfusions. PMID- 2875355 TI - Asthma mortality in England and Wales. PMID- 2875356 TI - Salmonella in vacuum cleaners. PMID- 2875357 TI - Misclassification as a factor in passive smoking risk. PMID- 2875359 TI - Presentation of variability. PMID- 2875358 TI - Ergotism as complication of thromboembolic prophylaxis with heparin and dihydroergotamine. PMID- 2875360 TI - Lipid peroxidation as cause of nigral cell death in Parkinson's disease. PMID- 2875361 TI - Serum aluminum and phosphate concentrations in CAPD. PMID- 2875362 TI - Coconut water and home rehydration. PMID- 2875363 TI - Methotrexate toxicity coincident with packed red cell transfusions. PMID- 2875365 TI - The Chernobyl accident. PMID- 2875364 TI - Death of patient after delayed response from deputising service. PMID- 2875366 TI - [Political economic significance of rehabilitation cures]. PMID- 2875367 TI - [Population forecasts, use, methods, reliability and problems. Use of population forecasts]. PMID- 2875369 TI - [Insurability of patients surviving myocardial infarcts]. PMID- 2875368 TI - [Life expectancy in heart failure]. PMID- 2875370 TI - [Insurance potential for patients with heart valve prostheses]. PMID- 2875371 TI - [Prognostic criteria in dialysis and kidney transplantation]. PMID- 2875372 TI - [Pathogenesis and therapy of hemorrhage in esophageal varices]. PMID- 2875373 TI - The emetic effect of B-HT 920 and apomorphine in the dog: antagonism by haloperidol. AB - Recent investigations have suggested that the alpha 2-adrenoreceptor agonist B-HT 920 is also a dopamine (DA) agonist with a selectivity for presynaptic receptors. In the present study, the emetic effect of B-HT 920 was investigated. Intravenous injections of B-HT 920 (0.32-10.0 micrograms/kg) and a DA2-agonist apomorphine (3.2-100.0 micrograms/kg) caused dose-dependent emesis. The ED50 of B-HT 920 and apomorphine were 3.2 and 12.3 micrograms/kg, respectively. When haloperidol (10.0 24.5 micrograms/kg i.v.), a DA2-antagonist, was given 5 minutes before B-HT 920 (10 micrograms/kg) or apomorphine (32 micrograms/kg), it caused a dose-dependent prevention of B-HT 920- and apomorphine-induced emesis. The ED50 of haloperidol in preventing the emetic effect of both drugs was identical (13.5 micrograms/kg). In contrast, haloperidol (32 micrograms/kg i.v.) did not prevent the emetic effect of ouabain (40 micrograms/kg i.v.). Neither did yohimbine (0.1 mg/kg i.v.), an alpha 2-adrenoreceptor antagonist, prevent the emetic effect of B-HT 920 (10 micrograms/kg). These results suggest that B-HT 920, acting like apomorphine, induces emesis by activating DA2-receptors probably in the chemoreceptor trigger zone of the area postrema. PMID- 2875375 TI - [Criteria and methods for determining fatigue]. PMID- 2875374 TI - Phencyclidine-like behavioral effects in pigeons induced by systemic administration of the excitatory amino acid antagonist, 2-amino-5 phosphonovalerate. AB - A selective N-methyl-D-aspartate antagonist, DL-2-amino-5-phosphonovalerate, was found to produce PCP-like catalepsy, discriminative stimulus effects, and stereotyped operant responding in pigeons when administered intramuscularly. These results support the hypothesis that the behavioral effects of PCP-like drugs result at least in part from reduced neurotransmission at excitatory amino acid synapses utilizing N-methyl-D-aspartate preferring receptors. PMID- 2875376 TI - [Open clinical study of clotiazepam in psychiatry]. PMID- 2875377 TI - Exercise tolerance and compensatory sympathetic tone during beta-blockade after myocardial infarction. AB - Using chronically instrumented dogs with a healed anterior wall myocardial infarction, we have assessed the effect of acute beta-adrenergic blockade on exercise tolerance, left ventricular (LV) performance, and myocardial VO2. Mongrel dogs were instrumented with Doppler flow probes around the left circumflex coronary artery, LV pressure cells, epicardial ECG electrodes, and left atrial and coronary sinus catheters. Myocardial infarction was produced by ligation of the left anterior descending coronary artery at time of instrumentation (approximately 20% LV mass). After a 1-month recovery period, dogs were subjected to two identical submaximal graded exercise tests on a treadmill on separate days, once without (control) and once with (propranolol, 1 mg X kg-1, i.v.) acute beta-adrenergic blockade. Heart rate, LV pressure, dP/dt max, left circumflex blood flow velocity, and myocardial VO2 index were measured at each stage of the graded exercise test. All variables were significantly reduced from control during beta-block in exercise. beta-Adrenergic blockade in the presence of a 1-month-old anterior wall myocardial infarction did not compromise exercise capacity during submaximal exercise. PMID- 2875378 TI - Organization and expression of genes involved in the biosynthesis of 987P fimbriae. AB - A chromosomal DNA segment encoding the biosynthesis of 987P fimbriae was isolated by cosmid-cloning and subsequent subcloning into pBR322. The 12 kb DNA segment expressed five polypeptides with apparent molecular weights of 81,000, 39,000, 28,500, 20,500, and 16,500, respectively. The location of the corresponding genes was determined by insertional mutagenesis using Tn5. The 20.5 K polypeptide was identified as the 987P fimbrial subunit by its reaction with specific anti-987P antibodies. The 81, 39, and 28.5 K polypeptides appeared to be accessory proteins involved in 987P production. PMID- 2875380 TI - Colonization of enterotoxigenic Escherichia coli exhibiting mannose-sensitive hemagglutination to the small intestine of piglets. PMID- 2875379 TI - The tobacco mitochondrial ATPase subunit 9 gene is closely linked to an open reading frame for a ribosomal protein. AB - A transcribed segment of mitochondrial DNA (mtDNA) from Nicotiana tabacum contains the F0-ATPase subunit 9 gene, an open reading frame with homology to the E. coli small subunit ribosomal protein S13 and an open reading frame with homology to a portion of the mammalian "URF 1" protein, recently shown to be a component of the NADH:ubiquinone reductase complex (NADH:Q 1). The transcriptional patterns of the tobacco ATPase 9 gene and S13-like open reading frame share eight RNA species indicating the two sequences are part of the same transcriptional unit. A maize mtDNA fragment contains the S13 homologous sequence and the NADH:Q 1 homologous sequence in an orientation similar to tobacco. The S13-like sequence is present as a single copy in maize and tobacco, as two copies in wheat, and is absent in pea and bean. We discuss the distribution and orientation of the S13-like and "URF 1"-like sequences and the possibility that they are active genes. PMID- 2875381 TI - Serotype and drug susceptibility of Bordetella pertussis isolated in Japan from 1975 to 1984. PMID- 2875382 TI - A probable new adhesive factor (F42) produced by enterotoxigenic Escherichia coli isolated from pigs. AB - Three enterotoxigenic Escherichia coli (ETEC) strains (coded 62, 104, and 567/7) isolated from piglets with neonatal diarrhea produced only a thermostable enterotoxin. Although these strains showed mannose-resistant microhemagglutination (MRMH), the responsible factor was serologically different from the known hemagglutinating colonization factors from porcine strains (K88, K99, and F41). Bacterial cells from these strains adhered to HeLa cells and pig brush borders. Electron microscope studies revealed the presence of fimbria-like structures on bacterial cells grown at 37 C but not on cells grown at 18 C. The antiserum prepared from partially purified fimbrial antigen (provisionally called F42) inhibited chicken erythrocyte MRMH caused by these strains as well as adherence of strain 567/7 to HeLa cells and to pig brush borders. These data taken together suggest the existence of a new hemagglutinating adhesin that is different from those so far described for porcine ETEC. PMID- 2875383 TI - Prescribing for the patient with renal disease. PMID- 2875384 TI - Rapid neuromuscular blockade: are there alternatives to succinylcholine? PMID- 2875385 TI - [Polyarteritis nodosa in childhood. A clinical contribution with special reference to renal damage]. PMID- 2875386 TI - [Physiopathology of human pancreatic polypeptide (hPP)]. PMID- 2875387 TI - [Oral hypoglycemics and insulin action. Post-receptor effects]. PMID- 2875388 TI - [Hydroxyzine and flunarizine as premedication for local anesthesia in allergic patients or patients with drug intolerance]. PMID- 2875389 TI - [Control of food intake]. AB - The decisions of an individual about his food intake depend upon a variety of internal and external signals. The present contribution describes the physiological mechanisms controlling food intake to preserve body composition and performance. Centers within the hypothalamus including their connections to higher and lower structures within the central nervous system, especially to the limbic system, are involved in the control a food intake. Neuropeptides and neurotransmitters usually initiate more complex actions including the search for food and satiety phenomena. Their production and release are influenced by food consumption as well as intake of specific nutrients, sensorial perceptions, and a variety of other factors. Vagal reflexes and gastro-intestinal hormones, fat cell size, physical activity, and thermogenesis also influence perceptions of hunger and satiety. A model satisfactorily describing the interactions between all known factors that control food intake is still missing. The path from hunger to satiety could be described as sequences of cascades similar to the various steps in blood clotting. Control of food intake during early life dependably relies on energy requirement, and can be utilized for ad-libitum feeding. Obesity and anorexia nervosa are manifestations of disturbed control over food intake. Neuropharmacology offers several therapeutic approaches to specific conditions. However, by and large abnormalities of food intake control have to be treated by behavioral modification. PMID- 2875390 TI - The carcinoid syndrome. PMID- 2875391 TI - Control of asthma by aerosols. PMID- 2875392 TI - Differential cross-tolerance among morphine, methadone, and ethylketocyclazocine- EEG and behavior. PMID- 2875393 TI - Physical dependence of benzodiazepines in the rat and dog. PMID- 2875394 TI - Stimulant depressant report. PMID- 2875395 TI - L-654,284 a new potent and selective alpha 2-adrenoceptor antagonist. AB - L-654,284 [(2R, 12bS)-N-(1,3,4,6,7,12b-hexahydro-2H-benzo[b]-furo[2,3-a] quinolizine-2-yl)-N-methyl-2-hydroxyethanesulfonamide) was tested in several in vitro and in vivo models for alpha 2-adrenoceptor antagonist activity and compared to several reference agents. In vitro L-654,284 completed for the binding of 3H-clonidine or 3H-rauwolscine (Ki's 0.8 nM, 1.1 nM) and blocked the presynaptic effects of clonidine in the rat isolated vas deferens (pA2, 9.1). L 654,284 exhibited marked alpha 2-vs. alpha 1-adrenoceptor selectivity in vitro, inhibiting 3H-prazosin binding with a Ki of 110 nM and blocking the effects of methoxamine on the vas deferens with a pA2 of 7.5. In vivo L-654,284 at 22 nmoles/kg i.v. doubled the ED50 of clonidine to produce mydriasis in rats. Given orally, the potency of L-654,284 in this test was reduced by a factor of 5.5. L 654,284 also potently increased cerebrocortical NE turnover in the rat, another in vivo index of alpha 2-adrenoceptor blockade in the central nervous system. In the periphery, L-654,284 demonstrated alpha 2-adrenoceptor selectivity by preferentially blocking the pressor effects of UK 14304 versus those of methoxamine in the pithed rat. Overall, L-654,284 was generally a more potent alpha 2-adrenoceptor antagonist than RX 781094 with comparable alpha 2/alpha 1 selectivity and was several times more potent and alpha 2-selective than WY 26703 or yohimbine. In addition, L-654,284 had better (5-6 times) oral bioavailability than RX 781094 or WY 26703. PMID- 2875396 TI - Sodium regulation of agonist and antagonist binding to beta-adrenoceptors in intact and Ns-deficient membranes. AB - Agonist binding to various hormone receptors mediating adenylate cyclase inhibition is decreased by sodium ions. We studied the influence of Na+ on agonist and antagonist binding to beta-adrenoceptors in membrane preparations of guinea pig lung, S49 lymphoma wild-type cells (WT) and their Ns-deficient cyc- variants by measuring binding of the antagonist, [125I]iodocyanopindolol [( 125I]CYP). At 37 degrees C, sodium decreased the receptor affinity for the agonist, isoproterenol, in all three membrane preparations. In lung and WT membranes, Na+ steepened the shallow agonist competition curves in a manner similar to and synergistic with guanine nucleotides. When binding was performed at 4 degrees C, sodium regulation but not guanine nucleotide regulation of agonist binding was preserved. At the low temperature, [125I]CYP affinity was reduced, and sodium increased [125I]CYP binding in both Ns-containing and Ns deficient membranes by increasing the antagonist affinity without significant change in total receptor number. Compared to Na+, Li+ and K+ were much less potent and efficient in decreasing agonist and increasing antagonist binding. Na+ and Mg2+ had opposite effects on agonist binding in the Ns-containing lung and WT membranes but not in the Ns-deficient cyc- membranes. The data indicate that sodium not only regulates binding of inhibitory hormone receptors but also agonist and antagonist binding to the adenylate cyclase stimulatory beta adrenoceptor. The finding that sodium regulation of beta-adrenoceptor binding is also observed in the Ns (alpha s)-deficient cyc- membranes, furthermore, indicates that the target of sodium is not the alpha-subunit of Ns but possibly a component common to both types of receptor systems regulating adenylate cyclase activity. PMID- 2875397 TI - Beta-adrenoceptor antagonists (non-selective as well as beta 1-selective) with partial agonistic activity decrease beta 2-adrenoceptor density in human lymphocytes. Evidence for a beta 2-agonistic component of the partial agonistic activity. AB - In the present study the effects of pindolol [non-selective beta-adrenoceptor antagonist with strong partial agonistic activity (PAA)] on beta 2-adrenoceptor density in lymphocytes (assessed by (-)-[125I]iodocyanopindolol (ICYP) binding) were compared with those of the beta 1-selective antagonists celiprolol (with PAA) and bisoprolol (no PAA) in normotensive young volunteers to get further insights into the nature of PAA. Administration of pindolol (2 X 5 mg/day) caused an about 25% decrease in lymphocyte beta 2-adrenoceptor density after 2 days; during treatment beta 2-adrenoceptor density declined further (maximum decrease after 7 days: 50%). After withdrawal of pindolol lymphocyte beta 2-adrenoceptor density recovered very slowly being still after 4 days significantly reduced, although no pindolol was detectable in plasma after 36 h. The KD-values for ICYP, however, did not change during or after pindolol treatment. The decrease in lymphocyte beta 2-adrenoceptor density induced by pindolol could be completely prevented by simultaneous administration of propranolol (3 X 40 mg/day) indicating that the PAA of pindolol is the cause of its beta-adrenoceptor decreasing effect. Administration of the non-selective beta-adrenoceptor antagonist bopindolol (1 X 2 mg/day) with PAA caused decreases in lymphocyte beta 2-adrenoceptor density (maximum decrease after 7 days: 40%); concomitantly the 10 mumol/l (-)-isoprenaline evoked increases in the intracellular level of lymphocyte cyclic AMP were attenuated to a similar extent indicating that the beta-adrenoceptor antagonist-induced decrease in beta-adrenoceptor density is accompanied by a loss in beta-adrenoceptor function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875398 TI - Relationship of metabolism of 2'-, 3'- and 5'-adenine nucleotides to presynaptic inhibition of transmitter release in rat vas deferens. AB - In the isolated rat vas deferens stimulated at 0.2 Hz, a series of 2'-, 3'-, and 5'-substituted adenine nucleotides all inhibited the twitch responses, their actions being potentiated by the nucleoside transport inhibitors, HNBTGR, NBMPR and dipyridamole. The metabolism of these nucleotides was examined utilizing HPLC analysis of the bathing medium after exposure to 30 microM nucleoside or nucleotide for 5 min. 5'-AMP, 5'-ADP, 5'-ATP, and NAD+ were all partially hydrolysed to adenosine, the relative extent of this being 5'-AMP greater than 5' ADP = 5'-ATP greater than NAD+. However, the other nucleotides examined were not detectably converted to adenosine or to adenosine deamination products. These results indicate that the 2'-, 3'- and 5'-substituted nucleotides studied act at a P1-purinoceptor in rat vas deferens to inhibit neurotransmission and, with the exception of 5'-AMP, 5'-ADP, 5'-ATP and NAD+, all appear to act directly at this receptor. However, the 5'-adenine nucleotides (AMP, ADP and ATP) and NAD+ all appear to act at least partially indirectly subsequent to their hydrolysis to adenosine. PMID- 2875399 TI - Quantitative electroencephalographic profile of 3-(4-hydroxy-1-piperidinyl)-6 (2,4-dichlorophenyl)-pyridazine (SR 41378) in the rat. AB - Quantitative electroencephalographic (QEEG) analysis was performed in rats following the oral administration of SR 41378 [3-(4-hydroxy-1-piperidinyl)-6-(2,4 dichlorophenyl)-pyridazine], a novel aminopyridazine derivative, which has been shown to possess anticonvulsant, antianxiety and hypnotic activities in mice and rats. The EEG effects of SR 41378 (10, 30 and 100 mg/kg) were compared to those of secobarbital (30 and 60 mg/kg) and diazepam (1, 3 and 10 mg/kg). SR 41378 and secobarbital increased the power of the middle-frequencies (8-16 Hz) of the EEG, reduced that of 4-8 Hz (theta) activities and did not affect 1-4 Hz (delta) activities. Diazepam also increased the power of middle-frequency activities and decreased that of both delta and theta activities. Quantitative EEG profiles were calculated from the mean integrated power (MIP) of selected frequency bands. The QEEG profile of SR 41378 was found to share common characteristics with those of secobarbital and diazepam: dose-dependent decrease of theta band MIP and increase of 8-20 Hz (middle beta bands) MIP. However, both SR 41378 and secobarbital induced a reduction of the 28-32 Hz (fast beta bands) MIP, whereas diazepam diminished the delta band. These results suggest that SR 41378, a novel chemical structure, shares common psychotropic properties with barbiturates and benzodiazepines. PMID- 2875400 TI - [Incidence and prevention of dental injuries in sports hockey]. PMID- 2875401 TI - Adrenergic and cholinergic stimulation of arachidonate and phosphatidate metabolism in cultured astroglial cells. AB - Primary cultures of neonatal rat brain polygonal astroglia, or cells of the C62B glioma line, were incubated with [1-14C]arachidonic acid (AA) in culture for 18 hr. In both culture systems, more than 80% of the added [1-14C]AA was taken up into cellular glycerolipids; less than 1% of the radioactivity in the cells was present in an unesterified form. When prelabeled C62B cells were stimulated with acetylcholine (ACh), there was a rapid accumulation of arachidonyl-phosphatidic acid (PA) accompanied by a liberation of [1-14C]AA. A variety of other neurotransmitters failed to activate this response in C62B glioma cells. In contrast to the agonist specificity of the response in C62B glioma cells, primary astroglia generated PA and liberated [1-14C]AA in response to several neurotransmitters (i.e., ACh, norepinephrine, glutamate, and histamine) Treatment of astroglia with a combination of norepinephrine, ACh, and histamine resulted in a greater production of PA and free [1-14C]AA than did treatment with any one of these neurotransmitters alone. The results suggest that cultures of astroglia can respond to several different neurotransmitters with specific changes in AA and PA metabolism. Thus, a variety of neurotransmitters initiate cascades of lipid metabolism which may be of physiological significance in glial function. PMID- 2875402 TI - Early partial reperfusion in a new rat model of focal cerebral ischaemia. AB - The influence of early partial reperfusion in a new rat model of focal cerebral ischaemia was investigated. Two groups, each of 30 adult male rats, were subjected to permanent occlusion of the right middle cerebral artery. The former, (group A) had an additional permanent occlusion of both common carotid arteries; the latter (group B) had a temporary carotid occlusion lasting for two hours. Mortality rate, evaluated within three days, was 70% in group A and 20% in group B. The mean size of cerebral infarcts was 63% in group A whereas it was 21% in group B. These data suggest that, in this animal model, early partial reperfusion is effective in reducing the mortality rate, and the size of the cerebral infarcts. Furthermore, this experimental model appears suitable for studies elucidating the role of reperfusion and/or other efforts in focal cerebral ischaemia. PMID- 2875404 TI - Intra-operative embolization of cerebral arteriovenous malformations by means of isobutylcyanoacrylate (experience in 20 cases). AB - 20 cases of cerebral arteriovenous malformations (AVM's) are reported, treated by direct intraoperative embolization. A 50% mixture of butyl-2-cyanoacrylate (IBC) and ethyl mono-iodostearate (Duroliopaque) was used. The clinical history of the patients was a long history of seizures in 10 cases, a haemorrhage in 9 cases, and a motor deficit in 1 case. In the immediate post-operative course, 1 patient died, 3 patients had a serious post-operative haemorrhage, 6 patients presented with a transient post-operative deficit, and in 10 patients the post-operative course was uneventful. During the following years, a late haemorrhage occurred after incomplete AVM eradication in 3 patients, leading to AVM resection. The AVM eradication was eventually complete in 3 cases with embolization only, and in 7 cases with embolization and AVM resection. The overall management of AVM in all 20 patients was: embolization only in 13 cases, embolization and resection in 7 cases. The long term results are: operative death 1, late death 3, long lasting deficit 1; uneventful 15. The authors discuss the technique of embolization, the effect of IBC on the vessel walls, the evolution of their general management of AVM's after this experience. Eventually the intra-operative embolization may be helpful after incomplete intra vascular embolization, to facilitate the AVM eradication. PMID- 2875403 TI - Analysis of epidural pressure pulse wave (EDP-PW) and common carotid blood velocity (CBFV) in acute intracranial hypertension. AB - The changes in the two consistent components of epidural pressure pulse wave (EDP PW), P1 and P2 waves, and mean velocity of common carotid blood flow (CBFV) were studied in 21 patients with acute intracranial hypertension to investigate the origin of th the amplitude change in these components. The amplitudes of P2 wave increased progressively with the rise of EDP, but those of P1 wave remained nearly invariable at EDP of more than 20-30 mmHg which is incompatible with the changes in CBFV. Jugular vein compression caused in rapid rise of EDP and a proportionate increase in the magnitudes of both waves. Hyperventilation and mannitol administration caused a disproportionate reduction in the amplitudes of P2 wave with a fall of EDP. But mannitol at high EDP (more than 40 mmHg) caused a mild fall of EDP and some increase in the amplitudes of P2 wave. These results indicate that the variations in the amplitudes of P1 wave reflect the changes in vascular resistance of the large intracranial conductive arteries, while those of P2 wave result from the changes in the volume of the cerebral bulk. The increase in the amplitudes of P2 wave induced by mannitol at high EDP may suggest a defective autoregulation of the cerebral vessels. PMID- 2875405 TI - Findings confirming brainstem generators of auditory evoked potentials by stereotactic lesions in the rabbit. AB - The origin of brainstem auditory evoked potentials (BAEP) was investigated experimentally with morphologically verified stereotactic lesions in eleven rabbits. Waves were recorded before and after thermocoagulation. The loss of waves III and V following coagulation in the inferior colliculus and the upper pons respectively, supports Jewett's hypothesis. PMID- 2875406 TI - Donor nerves in the reinnervation of brachial plexus. AB - In cases of brachial plexus spinal root avulsions the only possibility for surgical treatment is reinnervation of plexus by cross-anastomosis with intact nerves. As donor nerves for reinnervation the adjoining (upper intercostal and spinal accessory) or regional intact nerves can be used. In this paper an analysis of these nerves on histological preparation from 15 autopsies and analysis of surgical results from 13 operated patients with total or partial spinal root avulsions are presented. The advantages of pure motor, especially regional, nerves and possibility of combined use of all donor nerves are emphasized. PMID- 2875408 TI - Development of new cerebral protective agents: the free radical scavengers. AB - The generation of the free radical reaction in the ischaemic and hypoxic brain has been demonstrated using the chemiluminescence and the ESR techniques. The effects of various drugs, thought to be free radical scavengers were then tested in the ischaemic brain of dogs. It was found that not only mannitol, but also vitamin E, dexamethasone and other drugs have significant cerebral protective effects--particularly when administered together. Moreover, remarkable improvements were found when these 3 drugs were administered with the artificial blood substitute, PFC, which is known to have a high oxygen-carrying capacity. Finally, using the chemiluminescence and the ESR method, we have demonstrated that mannitol, vitamin E and glucocorticoids act as free radical scavengers and particularly mannitol acts as a scavenger of the hydroxy radical. PMID- 2875407 TI - Potential ganglioside antigens associated with human gliomas. AB - Gangliosides in human gliomas were investigated and found to have an altered composition and concentration as compared to normal grey and white matter of brain. The major gangliosides GM1, GD1a, and GT1b were markedly reduced in the tumour tissue and in contrast there was an increase of gangliosides GM3 and GD3, which often appeared as the dominating ones. Moreover, the tumours contained gangliosides, both mono- and oligosialylated, which could not be detected in the normal brain. The concentration of gangliosides, 0.7 +/- 0.4 mumol sialic acid/g, was significantly lower as compared to normal brain grey (p less than 0.001) and white matter (p less than 0.01), which contained 3.5 +/- 0.3 and 1.2 +/- 0.3 mumol sialic acid/g respectively. The tumour tissue concentration of phospholipids was 14 +/- 8 and of cholesterol 19 +/- 12 mumol/g. The appearance in glioma tissue of gangliosides that are not found in normal brain tissue suggests that these are tumour associated and might serve as surface antigens detectable by specific monoclonal antibodies. PMID- 2875409 TI - Interleukin-2 and lymphokine activated killer (LAK) cells in the treatment of malignant glioma: clinical and experimental studies. AB - The phenomenon of glioma killing by lymphokine activated killer cells (LAK) was studied. We demonstrate that LAK cells generated by culturing the lymphokine interleukin-2 (IL-2) with peripheral blood lymphocytes from brain tumour patients destroys autologous glioma. The rat 9L glioma model was used to show that LAK killing was tumour-selective as glioma but not syngeneic normal brain tissue was destroyed. The susceptibility of both human and 9L rat glioma to LAK cell killing was markedly diminished by pretreating glioma cells with trypsin or chymotrypsin, but was unaffected by pretreatment with neuraminidase, glycosidases, sodium periodate or hydrocortisone. These results suggest that the cell surface determinant on glioma cells responsible for its tumour selective lysis by LAK is a protein sensitive to trypsin and chymotrypsin. The tumour-selective killing of glioma by LAK in vitro prompted the initiation of a Phase I study in which ten patients with malignant glioma have been treated with direct intracerebral injection of IL-2 or LAK without evidence of systemic or brain toxicity. PMID- 2875410 TI - Screening and treatment of unruptured cerebral aneurysms. AB - Thirty outpatients with unruptured cerebral aneurysms screened by computed angiotomography have been analysed and followed up in our clinic since 1979. Seventeen were men and the age range was 41 to 74 years old (mean 57.7 years). Patients had no or only mild neurological symptoms, such as headache, sensorimotor or speech impairment and others, which were scarcely related to the unruptured aneurysms themselves. It is important to realize that these first aneurysms which remain unruptured, have a primary significance to the individual in the protective aspect of an initial subarachnoid haemorrhage. Operation was successfully performed in fifteen patients. Transient aggravation of previous diseases, e.g. cerebral infarction, occurred in three after operation. Follow-up studies of fifteen patients without operation revealed no change in eight and some worsening or death due to other or previous diseases in six. One died of aneurysmal rupture in the 5th month after its detection. Because of the low operative risk, we advocate the operative treatment of unruptured aneurysms, following careful selection of the indicated patients. PMID- 2875411 TI - Non-invasive measurement in intracranial pressure and analysis of the pulse waveform. AB - Non-invasive measurement of the intracranial pressure (ICP) via the anterior fontanelle by using an applanation transducer has been performed. Recently, a new fontanometer using an applanation transducer has been developed in our department by improving the conventional Statham transducer, P-50 which is currently accepted for its high reliability. In this study, by analysing patterns of the ICP pulse waves obtained from this new fontanometer, its clinical evaluation has been made in 27 neonates and infants in intracranial pathologies. Analysing the ICP waveforms, the first peak (P1) was divided by the following second peak (P2) and the changes in P1/P2 were examined. A differential amplifier, a dP/dt detector, was also used to make it easier to identify the turning point on the pulse waves. The results obtained demonstrated that the waveforms of ICP in neonates as well as infants are influenced by not only the intracranial constituents but compliance of the container such as the scalp, cranium and the meninges. PMID- 2875412 TI - Inhibition of hyperactive trigeminal subnucleus caudalis neurons after experimental trigeminal rhizotomy in response to thalamic sensory relay nucleus stimulation. AB - The effects of thalamic sensory relay nucleus stimulation on the single neuron activity and field potentials within the trigeminal subnucleus caudalis, which is trigeminal equivalent of the dorsal horn were investigated in intact cats as well as in cats subjected to retro-Gasserian rhizotomy 1-6 months before the experiments. Inhibition of nociceptive neural activity and a positive field potential were evoked by thalamic stimulation in the dorsal horn of the intact animals. A positive field potential followed double pulse stimulation with frequencies ranging up to approximately 50 Hz. The inhibitory periods ranged from 60 to 100 ms. Train pulse stimulation with frequencies ranging from 30 to 50 Hz produced long-lasting inhibition of nociceptive neural activity and a positive shift of the field potentials. Essentially identical inhibition of abnormal neural hyperactivity occurring in the rhizotomized dorsal horn was observed. The positive field potential corresponding to this inhibition also displayed characteristics similar to the field potential seen in the intact dorsal horn. These data indicate that the pathways involved in the inhibitory responses induced by thalamic sensory relay nucleus stimulation, unlike some other pain inhibitory systems, can exert their influence even to the dorsal horn which has undergone reorganization of neural circuits after rhizotomy. PMID- 2875413 TI - Stereoselectivity of central alpha-adrenoceptors involved in sleep induced by clonidine in chickens. AB - The stereoselectivity of central alpha 2-adrenoceptors involved in sleep induced in chicks by clonidine, suggested by the results observed with the stereoisomers of idazoxan, was further investigated with the stereoisomers of (imidazolinyl-2) 2-dihydro-2,3-benzofurane (S9871) and those of (imidazolinyl-2)-2 benzocyclobutane (S10089). As for the stereoisomers of idazoxan, there was not a good separation between the effects of the stereoisomers of S10089. In contrast, there was a clearcut separation between the effects of (+)S9871 (antagonist) and (-)S9871 (no effect against the action of clonidine). Therefore, these results strongly support the view that central alpha 2-adrenoceptors which mediate sedation are stereoselective for alpha 2-antagonists. PMID- 2875414 TI - A potent factor in extracts of the skin of the Australian frog, Pseudophryne coriacea. Apparent facilitation of transmitter release in isolated smooth muscle preparations. AB - Extracts of the skin of the Australian frog Pseudophryne coriacea (PsC) displayed potent stimulant effects on isolated smooth muscle preparations of intestine and similar effects on electrically-stimulated vas deferens preparations. These effects must be ascribed to an alkaloid, related in structure to the pumiliotoxins, a class of alkaloid compounds occurring in the skin of neotropical poison frogs. On the basis of results obtained with antagonists and blocking agents, it is suggested that the extract has a pre-synaptic, neurogenic point of attack and that it acts to facilitate the release of transmitters from nerve endings. Acetylcholine is the most important agent involved in the response to the extract by the intestinal muscle and noradrenaline in the response by vas deferens preparations. However, release of other aminergic or peptidergic transmitters may participate, positively or negatively, in the response. PMID- 2875415 TI - Proposals for the classification and nomenclature of functional receptors for 5 hydroxytryptamine. AB - As a result of controversy in the literature regarding the classification and nomenclature of functional receptors for 5-hydroxytryptamine (5-HT), a framework for classification is proposed. The formulation of these proposals has only been made possible by the recent advent of new drug tools. It is considered that there are three main types of 5-HT receptor, two of which have been well characterised pharmacologically, using selective antagonists, and which it is proposed to name 5-HT2 and 5-HT3. These two groups broadly encompass the "D" and "M" receptors, respectively, which Gaddum identified in the guinea-pig ileum (Gaddum and Picarelli, 1957). The 5-HT2 receptor, which mediates a variety of actions of 5 HT, has been definitively shown to correlate with the 5-HT2 binding site in the brain. No binding studies in brain tissue have yet been published with radiolabelled ligands specific for 5-HT3 receptors. A number of other actions of 5-HT appear to be mediated via receptors distinct from 5-HT2 or 5-HT3 receptors. Since selective antagonists are not yet available, these receptors cannot be definitively characterised, although in many cases they do have some similarities with 5-HT1 binding sites, which are a heterogeneous entity. Criteria are proposed for tentatively classifying these receptors as "5-HT1-like" (Table 1). Definitive characterisation of these receptors will await the identification of specific antagonists. This classification of 5-HT receptors into three main groups (Table 1) is based largely, but not exclusively, on data from studies in isolated peripheral tissues where definitive classification is possible. However, it is believed that this working classification will be relevant to functional responses to 5-HT in the central nervous system. PMID- 2875416 TI - The sites and mechanisms of action of 2-di-n-propylamino-5, 6-dihydroxytetralin in the hypothalamus of the rat to modify gastric secretion. AB - Rats were implanted with chronically indwelling gastric and intracerebral cannulae for the analysis of the hypothalamic sites and mechanisms of action of the dopamine agonist, 2-di-n-propylamino-5,6-dihydroxytetralin, to reduce the volume of gastric secretion and concentration of acid. The hypothalamic areas most sensitive to the actions of the tetralin compound to modify gastric secretion were the ventromedial and dorsomedial nuclei. Movement of the injection site 0.5 or 1.0 mm away from the ventromedial and dorsomedial nuclei in the anterior, posterior or lateral direction led to reduced effectiveness, or loss of action. In a study restricted to the ventromedial nucleus of the hypothalamus, the tetralin compound (0.1-5 micrograms) was shown to cause dose-dependent changes in gastric secretion, the reduction in concentration of acid being antagonised by the neuroleptic agents, sulpiride, metoclopramide, cis flupenthixol and haloperidol, and by the alpha 2-adrenoceptor antagonist, yohimbine injected at the same site. The reduction in secretory volume was antagonised by propranolol. Thus, a locus specificity was shown for the action of the tetralin compound in the dorsomedial and ventromedial hypothalamic nuclei of the rat, to reduce the volume of gastric secretion and concentration of acid. Such actions, as assessed in the ventromedial nucleus, are initiated via neuroleptic-sensitive, dopamine receptor mechanisms with additional involvement of alpha 2-adrenoceptors in the control of change in concentration of acid, and beta-adrenoceptors in the change in volume of secretion. PMID- 2875417 TI - The role of metabolism in the action of prolyl-leucyl-glycinamide on the development of tolerance to the analgesic effect of morphine. AB - Administration of melanotropin release inhibiting factor, a tripeptide (Pro-Leu Gly-NH2) has been shown to inhibit the development of tolerance to opiates. In order to understand the mechanism by which this effect is produced, the effects of the possible metabolites of Pro-Leu-Gly-NH2 on the development of tolerance to the analgesic effects of morphine were determined in male Sprague-Dawley rats. Rats were made tolerant to morphine by the subcutaneous implantation of four pellets of morphine over a 3-day period. Each pellet contained 75 mg of morphine, free base. Rats serving as controls were implanted with placebo pellets. Following implantation of the morphine-containing pellets, tolerance developed to the analgesic effect of morphine as shown by the decreased response to morphine. Subcutaneous injections of Pro-Leu-Gly-NH2, Pro-Leu-OH or Leu-Gly-NH2 (10 mumol/kg per day), prior to and during the implantation of pellets, inhibited the development of tolerance to morphine. However, Pro-Leu-Gly-OH and Leu-Gly-OH, administered in the same dose as the other compounds, had no effect on the development of tolerance to the analgesic effect of morphine. It is concluded that the inhibitory effect of Pro-Leu-Gly-NH2, which has a short biological half life, may be mediated by its conversion to active metabolites. PMID- 2875418 TI - Cell suspension grafts of noradrenergic locus coeruleus neurons in rat hippocampus and spinal cord: reinnervation and transmitter turnover. AB - Fetal noradrenergic neurons from the brain stem locus coeruleus region can be successfully grafted as a dissociated cell suspension provided that the dissociation is done in the absence of any trypsin digestion step. The survival, fiber outgrowth and biochemical function of locus coeruleus neurons, taken from 13- to 15-day-old rat embryos, have been studied after injection into the dorsal hippocampal formation and the thoracolumbar spinal cord in adult rats. All rats were treated with an i.v. injection of 6-hydroxydopamine prior to grafting to remove the intrinsic locus coeruleus projections to these areas, and they were taken for fluorescence histochemical or biochemical analyses 2-7 months after transplantation. Up to 330 surviving noradrenaline neurons were found at each implantation site (injected with 2-3 microliters of cell suspension) which represents an estimated survival rate of about 40%. In the most successful cases the entire dorsal hippocampal formation, and an approximately 4 cm long segment of the thoracolumbar spinal cord, was supplied with a new noradrenaline containing terminal network, which reached normal densities in the regions closest to the grafts. In the hippocampal formation, in particular, the ingrowing axons re-established a laminar innervation pattern which resembled that of the normal locus coeruleus afferents. In the hippocampus, two 2-microliters injections of locus coeruleus cell suspension restored the total hippocampal noradrenaline content to an average of 55%, and the noradrenaline synthesis rate (as assessed by the rate of DOPA accumulation after synthesis inhibition) was found to be close to normal in the graft-reinnervated specimens. In the spinal cord, two 3-microliters injections restored the noradrenaline level in the thoracolumbar cord (a 4.5 cm long segment) to an average of 22% of normal, with the highest individual levels being close to normal. Determinations of the noradrenaline metabolite 3,4-dihydroxy-phenylethyleneglycol indicated that the rate of noradrenaline metabolism in the graft-reinnervated spinal cord was close to that of the normal intact spinal cord. The results demonstrate the potential of the suspension grafting technique for extensive noradrenergic reinnervation of the hippocampal formation or large portions of the spinal cord. Fetal locus coeruleus neurons implanted in this way can re-establish fairly normal terminal innervation patterns and reinstate noradrenaline turnover and metabolism in a previously denervated central target. PMID- 2875419 TI - Somatostatin immunoreactivity in the entopeduncular projection to the lateral habenula in the rat. AB - Many neurons within the ipsilateral entopeduncular nucleus were retrogradely labelled following the stereotaxic injection of the fluorescent tracer True Blue into the lateral habenula of the rat. These neurons also displayed somatostatin immunoreactivity when examined with a monoclonal antibody to cyclic somatostatin. Excitotoxic lesions of the entopeduncular nucleus resulted in a loss of the dense somatostatin terminal field normally present in the lateral habenula. These results indicate that the neuropeptide somatostatin is present in the projection from the entopeduncular nucleus to the lateral habenula. PMID- 2875420 TI - Lesions to Schaffer collaterals prevent ischemic death of CA1 pyramidal cells. AB - The contribution of excitatory inputs to CA1 pyramidal cell death after ischemia was examined using rats with unilateral destruction of CA3 pyramidal cells. Intracerebroventricular injection of L-alpha-kainic acid (KA) was performed before the induction of transient forebrain ischemia. Five days after ischemic insult, pyramidal cells and L-glutamate binding sites in the CA1 region ipsilateral to the KA injection were preserved in spite of neuronal necrosis and a significant decrease in L-glutamate receptor density in the contralateral CA1 region, indicating the critical role of Schaffer collaterals in delayed neuronal death. PMID- 2875421 TI - Early and late effects of systemically administered 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) on tyrosine hydroxylase activity in vitro and on tyrosine hydroxylation in tissue slices of mouse striatum. AB - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces a parkinsonian-like state in humans and some animals. To compare the early biochemical abnormalities produced by this neurotoxin with late effects, we examined both in vitro tyrosine hydroxylase activity in striatal homogenates and in situ tyrosine hydroxylation in striatal tissue slices after single and repeated systemic injection of MPTP to mice. The acute administration of MPTP (30 mg/kg, s.c., 1 h prior to sacrifice) in mice resulted in a decrease of tyrosine hydroxylation in situ in tissue slices but not in vitro in homogenates. In contrast, repeated treatment of mice with MPTP (30 mg/kg, s.c. daily for 8 days) caused a decrease of tyrosine hydroxylase activity both in vitro in homogenates and in situ in tissue slices. These results suggest that MPTP inhibits tyrosine hydroxylation in dopaminergic neurons in an early stage and causes reduction of tyrosine hydroxylase itself after repeated administration. PMID- 2875422 TI - Picric acid-evoked release of [14C]acetylcholine from the isolated synaptosome of rat cerebral cortex. AB - Picric acid stimulated, in a dose-dependent manner, the release of [14C]acetylcholine (ACh) from isolated synaptosomes of rat cerebral cortex pre loaded with labelled choline. Radioactive ACh was separated for counting from choline in the synaptosomal supernatants by a liquid cation-exchange method. Neither the nicotinic antagonist (hexamethonium) nor the muscarinic antagonists (atropine and scopolamine) affected the effectiveness of picric acid, suggesting that the action of picric acid does not occur through a cholinoceptor-mediated mechanism. Moreover, oxotremorine, but not pilocarpine, inhibited ACh release in a concentration-dependent manner in either basal- or picric acid-evoked conditions, indicating the presence of muscarinic M2-receptors for auto regulation of ACh release. The effect of picric acid was compared with high-K+ depolarization which also initiated a non-receptor-mediated release of ACh. Deletion of calcium ion from the medium negated the effects of both drugs. The ACh-releasing effect of picric acid was totally abolished, whereas high-K+ depolarization was reduced to some extent, when tetrodotoxin was added to the medium. These results indicate that picric acid acts as a releaser of ACh in the cerebrocortex of rat. PMID- 2875424 TI - Abstracts. Tenth European Neuroscience Congress. Marseille, France, September 14 18, 1986. PMID- 2875423 TI - Blockade of N-methyl-D-aspartate-sensitive acidic amino acid receptors inhibits ischemia-induced accumulation of purine catabolites in the rat striatum. AB - The effect of blocking N-methyl-D-aspartate (NMDA)-sensitive excitatory amino acid (EAA) receptors during brain ischemia was studied in order to test a link between EAAs and neuronal energy metabolism. The receptors were blocked unilaterally in the rat striatum before, during and after an ischemic insult. The receptor blocker, D-2-amino-5-phosphonovalerate (D-APV) was administered by dialysis perfusion, which also allowed continuous sampling for analysis of adenosine triphosphate degradation products, i.e. purine catabolites, in control and D-APV-treated striata. Purine catabolites were analysed with reversed-phase liquid chromatography. Hypoxanthine, xanthine, inosine and adenosine increased dramatically in the striatum during ischemia and reached maximum levels during early reperfusion. D-APV reduced the extracellular accumulation of all measured purine catabolites during ischemia/reflow and improved to some extent the recovery of the striatal electroencephalographic activity in the majority of the animals. The results suggest that NMDA receptor blockade attenuates acute changes in energy metabolism during ischemia. PMID- 2875425 TI - Glutamate-elicited stimulation of acetylcholinesterase activity in cerebellar slices from newborn rats. AB - Bath application of glutamate at two concentration ranges, 10(-6)-10(-8) and 1-3 X 10(-3) M, effectively increased acetylcholinesterase activity in cerebellar slices obtained from 8-day-old rats. No such effect was seen in cerebellar slices of 7-week-old rats or cerebral slices of either 7-week or 8-day-old rats. Glutamic acid diethyl ester blocked the glutamate effect at both of these concentration ranges, suggesting that quisqualate-sensitive glutamate receptors are involved in regulation of acetylcholinesterase activity in early postnatal cerebellum. Since bath application of cyclic GMP at 10(-7)-10(-9) M increased the acetylcholinesterase activity in cerebellar slices of 8-day-old rats, it is possible that glutamate-dependent regulation of acetylcholinesterase activity is mediated by cyclic GMP. The observation that adenosine deaminase blocked the effect of glutamate completely at 10(-6)-10(-8) M and partially at 1-5 X 10(-3) M further suggests that release of adenosine is a link from enhanced cyclic GMP activity to activation of acetylcholinesterase. PMID- 2875426 TI - Clostridium difficile toxin in chronic idiopathic colitis. AB - Clostridium difficile toxin was isolated from the stools of three patients with chronic idiopathic colitis. Two patients were known to have chronic idiopathic colitis before Cl difficile toxin was isolated. The third patient was subsequently found to have ulcerative colitis after presentation with Cl difficile toxin in the stool. Two patients were on sulphasalazine at the time of diagnosis of Cl difficile infection and one had taken sulphasalazine two months previously. Only one patients had antibiotic exposure and that was at least three months before presentation. In each patient, treatment with vancomycin was accompanied by symptomatic improvement and disappearance of the toxin. The underlying colitis remained unaffected. In patients with inflammatory bowel disease in relapse, the presence of Cl difficile toxin should be sought as this may be a factor in the relapse. In any patient presenting with diarrhoea, the presence of Cl difficile toxin may obscure the presence of underlying inflammatory bowel disease. PMID- 2875427 TI - Stress-related, posttraumatic chronic pain syndrome: behavioral treatment approach. AB - Chronic pain syndromes are often the result of traumatic injury. The life threatening nature of a substantial number of these traumata precipitates the development of posttraumatic stress disorder in a sizable percentage of accident incurred chronic pain conditions. The present study presents evidence that systematic desensitization, a behavioral technique, can provide significant resolution of posttraumatic stress when this disorder occurs in the chronic pain population. PMID- 2875428 TI - [The 27th Congress of the CPSU and prospects for development of Soviet science]. PMID- 2875429 TI - [Ultrastructural signs of aging in gastric AL cells]. PMID- 2875430 TI - Death due to chronic syrup of ipecac use in a patient with bulimia. AB - A 17-year-old girl presented with malaise, weakness, palpitations, dysphagia, myalgias, and weight loss of 1 month's duration. Within 24 hours of admission to the hospital, she had hypotension unresponsive to medical management, intractable congestive heart failure, and arrhythmias; she died. Several empty bottles of syrup of ipecac were later found among her belongings. Syrup of ipecac is commonly used to induce emesis in patients who had ingested toxic substances. The chief pharmacologic property of this agent is due to its alkaloid component, emetine. There have been many previous reports of death due to emetine poisoning in patients receiving ipecac fluid extract and in those treated for amoebic dysentery. However, the literature cites only three case reports of fatalities secondary to chronic ipecac use as a means of losing weight. This is the first report of a death due to chronic ipecac use in an adolescent patient with bulimia. Emetine persists in the body for long periods, and in patients who have ingested it chronically, emetine is extremely toxic, specifically to cardiac smooth and skeletal muscles. With an increased awareness of the importance of weight control in the adolescent age group, the physician must carefully evaluate these patients for the use of emetics. PMID- 2875431 TI - [Use of beta-adrenoblockaders in young children with tetralogy of Fallot]. PMID- 2875432 TI - Transmitter release from nerve terminals evoked by depolarization pulses contains a short phase of repression. AB - The time course of quantal transmitter release after a depolarization pulse was measured at frog and crayfish motor nerve terminals. Test pulses were arranged to elicit low release, and the delay of first releases and the median of distributions of release times were defined for large (greater than 2000 stimuli) samples. Small, subthreshold depolarizing post-pulses were added directly after the test pulses. Such post-pulses of 1 to 4 ms duration prolonged the delay of first releases and shifted the median of the time course of release by up to 3 ms (at 0 degree C) depending on the duration and on the amplitude of the post pulses. These 'latency shifts', which have been observed after prolonged depolarizations by other authors, were statistically highly significant. The results of post-pulses were very similar at neuromuscular junctions of frog and crayfish. It is concluded that depolarization in addition to the promotion of release has a short repressing action on release which is partly responsible for synaptic delay. PMID- 2875433 TI - Transcript termini of messenger RNAs in higher plant mitochondria. AB - The 3'-termini of the mRNAs for subunit II of the cytochrome oxidase (COX II) and for the alpha-subunit of the mitochondrial ATPase (ATPA) have been determined in Oenothera mitochondria by two independent methods. Analysis of both transcripts by S1 protection experiments and of cloned cDNAs show an identical terminal 50 nucleotide sequence, to which homology is found 3' to some gene sequences in the maize mitochondrial genome. These regions can be folded into potential secondary structures similar to bacterial terminators. PMID- 2875434 TI - Molecular cloning and complete primary sequence of human erythrocyte porphobilinogen deaminase. AB - We have cloned and sequenced a cDNA clone coding for human erythrocyte porphobilinogen deaminase. It encompasses the translated region, part of the 5' and the 3' untranslated regions. The deduced 344 amino acid sequence is consistent with the molecular weight and the partial amino-acid sequence of the NH2 terminal of the purified erythrocyte enzyme. Southern analysis of human genomic DNA shows that its gene is present as a single copy in the human genome and Northern analysis demonstrates the presence of a single size species of mRNA in erythroid and non-erythroid tissues and in several cultured cell lines. Quantitative determinations indicate that the amount of PBG-D mRNA is modulated both by the erythroid nature of the tissue and by cell proliferation, probably at the transcriptional level. PMID- 2875435 TI - Infectious mutants of cassava latent virus generated in vivo from intact recombinant DNA clones containing single copies of the genome. AB - Intact recombinant DNAs containing single copies of either component of the cassava latent virus genome can elicit infection when mechanically inoculated to host plants in the presence of the appropriate second component. Characterisation of infectious mutant progeny viruses, by analysis of virus-specific supercoiled DNA intermediates, indicates that most if not all of the cloning vector has been deleted, achieved at least in some cases by intermolecular recombination in vivo between DNAs 1 and 2. Significant rearrangements within the intergenic region of DNA 2, predominantly external to the common region, can be tolerated without loss of infectivity suggesting a somewhat passive role in virus multiplication for the sequences in question. Although packaging constraints might impose limits on the amount of DNA within geminate particles, isolation of an infectious coat protein mutant defective in virion production suggests that packaging is not essential for systemic spread of the viral DNA. PMID- 2875437 TI - Cloning and sequence analysis of a cDNA for a rat liver glutathione S-transferase Yb subunit. AB - We have isolated a Yb-subunit cDNA clone from a GSH S-transferase (GST) cDNA library made from rat liver polysomal poly(A) RNAs. Sequence analysis of one of these cDNA, pGTR200, revealed an open reading frame of 218 amino acids of Mr = 25,915. The deduced sequence is in agreement with the 19 NH2-terminal residues for GST-A. The sequence of pGTR200 differs from another Yb cDNA, pGTA/C44 by four nucleotides and two amino acids in the coding region, thus revealing sequence microheterogeneity. The cDNA insert in pGTR200 also contains 36 nucleotides in the 5' noncoding region and a complete 3' noncoding region. The Yb subunit cDNA shares very limited homology with those of the Ya or Yc cDNAs, but has relatively higher sequence homology to the placental subunit Yp clone pGP5. The mRNA of pGTR200 is not expressed abundantly in rat hearts and seminal vesicles. Therefore, the GST subunit sequence of pGTR200 probably represents a basic Yb subunit. Genomic DNA hybridization patterns showed a complexity consistent with having a multigene family for Yb subunits. Comparison of the amino acid sequences of the Ya, Yb, Yc, and Yp subunits revealed significant conservation of amino acids (approximately 29%) throughout the coding sequences. These results indicate that the rat GSTs are products of at least four different genes that may constitute a supergene family. PMID- 2875439 TI - Effects of cognitive and pharmacologic strategies on analogued labor pain. AB - Using an analogued labor pain procedure, the efficacy of combinations of five cognitive and one pharmacologic approach to pain management was examined. Nulliparous undergraduates (N = 120) were randomly assigned to 1 of 12 groups. Cognitive groups included: systematic desensitization (SYS DENS); sensory description (SEN DESC); sensory transformation (ST); modeling (M); and relaxation (R); combined groups: SYS DENS, SEN DESC, and ST; SEN DESC, ST, and R; SEN DESC, R, ST, and Demerol. Pharmacologic groups included expected Demerol, did not expect Demerol, placebo, and no treatment control. Subjects assigned to a cognitive group received two 1-hour training sessions 1 week apart. Remaining subjects were given the assigned pharmacologic treatment one-half hour prior to the exposure to the painful stimulus. Assessment of the cognitive and pharmacologic approaches were made in a 1-hour session involving twenty 80-second exposures to a laboratory pain stimulus patterned to resemble labor contractions. Dependent variables included self-reported pain, blood pressure, frontalis electromyograph, heart rate, and respiratory rate. Significant treatment by trials and treatment effects were found for self-reported pain. No other effects achieved statistical significance. PMID- 2875436 TI - Cloning of a cDNA coding for P-450 LM3c from rabbit liver microsomes and regulation of its expression. AB - Liver cytochromes P-450 LM3c in the rabbit and P-450p in the rat are two related forms, inducible by macrolide antibiotics such as triacetyloleandomycin (TAO) and glucocorticoids such as dexamethasone. We prepared a cDNA library from TAO induced rabbit liver mRNA and characterized a cDNA (pLM3c-4.1) that hybridized to pDex 3.22, a cDNA complementary to cytochrome P-450p mRNA. Northern blots of liver poly(A)RNA from untreated or TAO, erythromycin and rifampicin treated animals, revealed two mRNA species of approximately 1700 and 1850 nucleotides in length, that hybridized to LM3c cDNA and to pDEX 3.22. The level of both mRNAs was increased five fold over control by macrolide antibiotics but unaffected by both phenobarbital and B-naphthoflavone. After 5 days of TAO treatment LM3c mRNA had increased 5 fold while LM3c protein had increased 25 fold. However, the rate of P-450 LM3c gene transcription measured in isolated liver nuclei remained unchanged throughout five days of TAO treatment. We conclude that TAO may induce cytochrome P-450 LM3c by post-transcriptional effects. PMID- 2875438 TI - Presence of a polyadenylated RNA fragment encoding the membrane domain for immunoglobulin alpha chain indicates that mRNAs for both secreted and membrane bound alpha chains can be produced from the same RNA transcript. AB - RNA blotting was employed to examine polyadenylated immunoglobulin alpha chain RNAs in a B lymphoma synthesizing membrane-bound and secretory IgA and in a hybridoma which synthesizes predominantly secretory IgA. Both cell lines were derived from the I.29 lymphoma and expressed the identical heavy chain variable region gene. In addition to the predicted mRNA precursors, four novel species of polyadenylated alpha RNAs were detected. The presence of a RNA species which was too large to have the same 3' end as the largest mRNA for membrane-bound alpha chain (alpha m) implied that transcription continued past the alpha m poly(A) site, and that such transcripts could be polyadenylated. Alternatively, transcription of this alpha RNA was initiated 5' to the normal cap site. Two species of RNA were detected which encoded the alpha m domain and the intervening sequence between the alpha constant (C alpha) and alpha m domain but not the C alpha domain. These RNA molecules were of sizes appropriate for their derivation by endonucleolytic cleavage of a precursor for alpha m mRNA at the poly(A) site of the mRNA for secreted alpha chains (alpha s). The presence of these three alpha RNA species suggested that alternative and successive cleavage/polyadenylation events could occur on a single transcript to produce either alpha m or alpha s mRNAs. An additional novel species of RNA was detected which indicated that the order of removal of the large IVSs did not always proceed in the 5' to 3' direction. PMID- 2875440 TI - Psychotropic medications. Nursing implications. AB - The purpose of this article has been to bring together selected critical information for the nurse to use in developing a plan of care for each individual patient in regard to psychotropic medications. The important considerations to keep in mind during assessment, planning, implementation, and evaluation have been discussed, with implications for the nurse in terms of her contribution to the treatment team's planning and evaluation of psychotropic drug therapy. In addition, patient education responsibilities have been addressed. The nurse is in a pivotal position to contribute significantly to the therapeutic effectiveness of each psychotropic medication treatment plan. PMID- 2875441 TI - Symptom distress in patients receiving Phase I chemotherapy with taxol. PMID- 2875442 TI - Somatocrinin stimulates adenylate cyclase-Ns regulatory subunit in a GH3 cell line: comparison with VIP. AB - We used a GH3 cell-line to compare the effects of rat GRF (rGRF) and VIP on the adenylate cyclase activity and to determine on what subunit the site of action of these two peptides is. In the GH3 cell-line, VIP was more potent than rGRF to stimulate adenylate cyclase activity. The stimulatory effects of rGRF and forskolin were additive. Cholera toxin decreased the apparent potency of these peptides and pertussis toxin reversed the inhibition by somatostatin of their adenylate cyclase stimulation. We conclude that rGRF acts on the regulatory subunit Ns, different from the regulatory subunit Ni on which somatostatin is suggested to be acting and that, in the GH3 cells, rGRF stimulates adenylate cyclase through VIP-preferring sites. PMID- 2875443 TI - Intercellular communication mediated by VIP in the cerebral cortex. AB - A growing number of biologically active peptides is being identified within the central nervous system (CNS). According to currently accepted criteria, several of these peptides, including VIP, can be viewed as neurotransmitters. Recent immunohistochemical and pharmacological investigations have been directed at the characterization of the position of VIP neurons in the circuitry of the cerebral cortex. From these studies some views on the possible function of VIP neurons in this CNS region are beginning to emerge. In the cerebral cortex, VIP neurons constitute a rather homogeneous population of intracortical, bipolar and radially oriented cells, which arborize locally, within cortical columns of 60-100 micron diameter. The cellular actions of VIP in the cerebral cortex include the stimulation of cAMP formation and of glycogen breakdown. A certain degree of cellular resolution of these two actions of VIP has been achieved by using purified preparations. Thus VIP stimulates cAMP formation in cerebral microvessels and in cultured astrocytes; in this latter cell type VIP also promotes glycogenolysis. Furthermore, VIP interacts synergistically with norepinephrine to stimulate cAMP formation and to inhibit the firing rate of spontaneously active identified cortical neurons. VIP neurons appear therefore to be strategically positioned to regulate the coupling between energy metabolism, blood flow and neuronal activity with great spatial selectivity and at a fine level of cortical resolution. PMID- 2875444 TI - Neurotransmitter-role of VIP in non-adrenergic relaxation of feline myometrium. AB - The feline myometrium is heavily innervated by VIP-containing nerve fibres. Transmural electrical stimulation (10 Hz, 2 msec, 150 mA) of muscle strips from feline myometrium in the presence of adrenoreceptor blocking agents caused a muscle relaxation. The smooth muscle relaxation was accompanied by a significant increase in immunoreactive VIP in the superfusate. Both the VIP release and the relaxation were completely annulled by tetrodotoxin, a selective blocker of axonal conduction. Furthermore, passive immunoneutralization with antiserum against VIP markedly reduced the smooth muscle relaxation induced by electrical stimulation. In the light of the previously demonstrated smooth muscle relaxant effect of VIP, the present findings indicate that the peptides may participate as neurotransmitter in non-adrenergic relaxation of the feline myometrium. PMID- 2875445 TI - Effects of dopaminomimetics on the secretion of VIP-like immunoreactivity in conscious dogs. AB - The effects of some dopaminomimetics on VIP levels in peripheral venous blood of conscious dogs were analysed with a radioimmunoassay. The dopamine D2 agonist pergolide, like apomorphine and bromocriptine, increased VIP levels. The putative DA autoreceptor agonist 3PPP, as well as the D1 agonist SK&F 38393 were devoid of action. The D1 antagonist SCH 23390 did not abolish the effect of apomorphine. It is suggested that monitoring of VIP levels could be an interesting screening test for activity at D2 receptors. Amphetamine did not modify VIP levels suggesting that DA neurons are not involved in the mechanism leading to a release of VIP. The VIP response to apomorphine was not suppressed by an infusion of somatostatin. Decreasing blood pressure with nitroglycerin or with the adrenergic antagonist prazosin did not release VIP. The mechanism by which administration of dopaminomimetics lead to a release of VIP is further discussed. PMID- 2875447 TI - Somatostatin enhances the inhibitory effect of oxyntomodulin and its C-terminal octapeptide on acid secretion. AB - Somatostatin (SOM) and oxyntomodulin (OXM) are two natural peptides present in the gut which display inhibitory effects on gastric acid secretion in rat. Possible interactions between the effects of these two molecules were tested in the anesthetized rat, using as the stimulant either pentagastrin or histamine at doses that induced 30% of the maximal responses. SOM was tested at sub-threshold doses and OXM at doses inducing an inhibition of less than 50%. SOM induced a highly significant potentiation of the action of OXM both on pentagastrin- and histamine-induced secretion. Similarly, SOM enhanced the inhibitory effects of the C-terminal octapeptide of OXM. Whatever the mechanism involved, this potentiating effect of SOM might be of importance in the in vivo biological effect of OXM. PMID- 2875446 TI - Neurohormonal regulation of secretin secretion in canine duodenal mucosa in vitro. AB - We examined the effects of cholinergic, peptidergic and GABAergic agents on secretin secretion from canine duodenal mucosal explants incubated in organ culture media. Carbachol (10(-12) to 10(-4) M), atropine (10(-6) to 10(-4) M), hexamethonium (10(-6) to 10(-4) M), and somatostatin did not alter basal secretion of secretin. Somatostatin (10(-7) to 10(-8) M) inhibited secretin secretion stimulated by pH 4.5. Met, Leu and their D-ala2-analogs inhibited both basal and pH 4.5-stimulated secretin. Naloxone reversed the inhibition caused by met-enkephalin at pH 7.4. GABA (10(-9) to 10(-6) M) stimulated both basal and pH 4.5-stimulated secretin secretion. GABA-stimulated secretin secretion was neuronal in nature, bicuculline sensitive and was mediated via post ganglionic cholinergic neurons. GABA-stimulated secretin secretion was inhibited by both somatostatin and metenkephalin, suggesting that GABA-stimulated secretin secretion may be under the inhibitory control of peptidergic agents as well. PMID- 2875448 TI - Analysis of somatostatin peptides produced by an endocrine pancreatic cell line. AB - Biological active forms of somatostatin are produced by cleavage of large precursors. If the sequence of the pre-proform of somatostatin has been deduced from cDNA structure in several species, little is known about the processing of these large precursors. For this purpose, the analysis of immunoreactive components secreted by the R.I.N. cell line was investigated. After selection of a cell population and culture conditions providing the optimal production of these peptides, analysis of their molecular forms was done by molecular gel filtration. The results show that mainly pro-forms accumulate in the culture medium while besides the pre-proform the smaller immunoreactive species behaving like S-28 and S-14 were found in cell extracts. Incorporation studies in serum free medium showed rapid formation of an intermediate compound eluted at 1.87 V0. PMID- 2875449 TI - Electrophysiologic effects of somatostatin in man. AB - Experimental and clinical studies suggest that somatostatin, a regulatory peptide widely distributed in human tissues may have electrophysiologic effects. We studied a group of 14 patients who underwent a complete electrophysiologic study for different rhythm disturbances. Somatostatin significantly increased the spontaneous cycle length, the atrial and atrioventricular nodal effective refractory periods, and the Wenckebach cycle length. The AH and HV intervals during sinus rhythm remained unchanged. The effectiveness of somatostatin to interrupt paroxysmal supraventricular tachycardias was assessed in 18 patients. Termination was obtained in 15 (82.5%). Our results show that somatostatin has a significant electrophysiologic effect on the human heart, and confirm its clinical effectiveness in some arrhythmias. PMID- 2875450 TI - Somatostatin response to a mixed meal in normals and in type I diabetics. AB - Somatostatin has been proposed as a regulatory peptide of nutrient entry and fuel homeostasis because of its ability to inhibit the release of substances involved in food digestion and metabolism. The aim of the study was to evaluate the somatostatin response to a test meal in type I diabetics at the clinical onset of the disease and after two months of intensive insulin therapy. Normal subjects and diabetics in good metabolic control showed a characteristic biphasic somatostatin rise after a test meal; this response was lacking in diabetics at the onset of the disease. The response of somatostatin to a mixed meal in normals confirms its involvement in nutrient digestion and metabolism. The lacking somatostatin response in newly diagnosed type I diabetics might be related to deficient GIP response to the test meal or to other factors such as the insulinopenia or metabolic derangement characteristic of the clinical onset of the disease. PMID- 2875451 TI - [Influence of new imaging technics on the structure and trends in the development of radiology. Introduction and purpose of the conference]. PMID- 2875453 TI - New insights into mechanisms of neuronal damage in the developing brain. AB - Hypoxia-ischemia, hypoglycemia, and status epilepticus damage specific regions in the developing brain. The factors which determine selective neuronal vulnerability have remained obscure but recent research suggests that the patterns may be related to dysfunction of specific sets of synapses. An important current hypothesis suggests that hyperactivity of excitatory synapses, which use neurotransmitters such as glutamate, may cause excessive transmitter release and lead to damage of adjacent neurons. Excessive stimulation of excitatory neurotransmitter receptors triggers a cascade of biochemical reactions and potentially lethal ionic shifts. Recent observations suggest that drugs acting at these receptors could be used to reduce brain injury caused by a variety of insults to the developing brain. PMID- 2875452 TI - The pharmacological profile of chlordesmethyldiazepam and other benzodiazepines. AB - The pharmacological profile of chlordesmethyldiazepam was studied in mice and compared with that of other benzodiazepines (diazepam, lorazepam, clonazepam, nitrazepam, oxazepam, flunitrazepam, medazepam and chlordiazepoxide). All the drugs were administered perorally and their anticonvulsive activity (antagonism towards pentetrazole-induced clonic convulsions), anxiolytic action (the four plate test), myorelaxant activity (the rota-rod test), sedative effect (inhibition of the locomotor activity) and neurotoxic effect (abolition of the righting reflex) were estimated. Chlordesmethyldiazepam revealed an anticonvulsive action (ED50 = 0.11 mg/kg), anxiolytic activity (MED = 2 mg/kg), myorelaxant action (ED50 = 17.5 mg/kg), sedative effect (ED50 = 34 mg/kg) and neurotoxic action (NTD50 = 190 mg/kg). Considering the potency of action (ED50) in respective tests and the therapeutic indices (NTD50/ED50 ratio), chlordesmethyldiazepam in respect of its profile resembles most lorazepam and diazepam. PMID- 2875454 TI - Neuroleptic malignant syndrome. An underdiagnosed reaction to neuroleptic agents? PMID- 2875455 TI - Beta-blockers and plasma potassium concentrations. PMID- 2875456 TI - [Ipecac poisoning]. PMID- 2875457 TI - The pseudopterosins: anti-inflammatory and analgesic natural products from the sea whip Pseudopterogorgia elisabethae. AB - The Caribbean sea whip Pseudopterogorgia elisabethae (Octocorallia, Cnidaria) has been found to contain the pseudopterosins, a newly described class of natural products, which have been characterized as diterpene-pentoseglycosides. The pseudopterosins possess anti-inflammatory and analgesic properties that exceed, in our assays, the potencies of existing drugs such as indomethacin. As anti inflammatory agents, the pseudopterosins appear to modify the arachidonic acid cascade by an as yet undefined mechanism of pharmacological action. PMID- 2875458 TI - Intracellular pools of transferrin receptors result from constitutive internalization of unoccupied receptors. AB - In HeLa cells the majority of transferrin (Tf) receptors are found within the endocytic apparatus, with only 20% of receptors exposed at the cell surface. Receptor distribution is unaltered by the presence or absence of Tf. The mechanism responsible for the cellular distribution of receptors was explored by selectively inactivating receptors within the endocytic apparatus. This was accomplished by employing Tf-horseradish peroxidase conjugates. Peroxidase catalyzed oxidation of diaminobenzidine within an endosome destroys Tf receptor activity. Using such conjugates, we have demonstrated that the majority of internal Tf receptors could be inactivated when less than 6.0% of receptors were occupied by the conjugate at steady state. This result indicates that occupied and unoccupied receptors are in the same compartment. Furthermore, horseradish peroxidase that was internalized by fluid-phase pinocytosis inactivated intracellular Tf receptors in the absence of Tf; this indicates that the presence of internal receptors is ligand independent. Following exposure of cells to the conjugate, receptor inactivation was proportional to the percentage of the endocytic cycle traversed by the conjugate--that is, the rate of ligand accumulation was the same as the rate of endosomal Tf receptor inactivation. When the Tf-horseradish peroxidase conjugate and 125I-labeled Tf were internalized simultaneously, both ligands were found in the same compartment. However, if the two ligands were administered as separate pulses and the period between pulses was as short as 1 min, the ligands remained separate within the cell. Together these results demonstrate that the intracellular pool of Tf receptors reflects the constitutive internalization of unoccupied Tf receptors, which, once internalized, remain segregated. PMID- 2875459 TI - Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. AB - We have examined the regulation of somatostatin gene expression by cAMP in PC12 rat pheochromocytoma cells transfected with the rat somatostatin gene. Forskolin at 10 microM caused a 4-fold increase in somatostatin mRNA levels within 4 hr of treatment in stably transfected cells. Chimeric genes containing the somatostatin gene promoter fused to the bacterial reporter gene encoding chloramphenicol acetyltransferase were also induced by cAMP in PC12 cells. To delineate the sequences required for response to cAMP, we constructed a series of promoter deletion mutants. Our studies defined a region between 60 and 29 base pairs upstream from the transcriptional initiation site that conferred cAMP responsiveness when placed adjacent to the simian virus 40 promoter. Within the cAMP-responsive element of the somatostatin gene, we observed an 8-base palindrome, 5'-TGACGTCA-3', which is highly conserved in many other genes whose expression is regulated by cAMP. cAMP responsiveness was greatly reduced when the somatostatin fusion genes were transfected into the mutant PC12 line A126-1B2, which is deficient in cAMP-dependent protein kinase 2. Our studies indicate that transcriptional regulation of the somatostatin gene by cAMP requires protein kinase 2 activity and may depend upon a highly conserved promoter element. PMID- 2875460 TI - Surface structure recognized for covalent modification of the aspartate receptor in chemotaxis. AB - The aspartate receptor involved in chemotaxis is modified by methyl esterification at four distinct glutamate residues during the adaptive response of this receptor. To explain the high degree of specificity of this modification, it has been proposed that the methyltransferase recognizes the sequence Glu-Glu Xaa-Xaa-Ala-Ser/Thr in an alpha-helical conformation and methylates the second glutamate in this sequence. This hypothesis is strengthened here by localized mutagenesis studies. By reversing the alanine-threonine sequence to threonine alanine at the principal site of methylation, Glu-309, a factor of 4 decrease in reactivity was achieved. Thus, the rate of methylation of this site is sensitive to the reversal of two residues of similar structure. These residues are somewhat distant in sequence from the glutamate that is modified but are adjacent in space if an alpha-helical structure is present. The other sites of modification, Glu 295, Glu-302, and Glu-491, are slightly increased in reactivity in the mutant. The 4-fold change in reactivity of the major site of methylation obtained with a relatively subtle change supports the recognition sequence hypothesis, including its structural implications. It is noted, in addition, that chemotaxis of bacteria expressing the mutant receptor does not seem to be greatly altered. This might be explained by the observation that the overall methylation levels of the mutant and wild-type receptors are similar. PMID- 2875462 TI - Gliogenesis: the importance of appropriate cell associations. PMID- 2875461 TI - Evidence for a central mechanism of obesity in the Zucker fatty rat (fa/fa). PMID- 2875463 TI - The role of the cell cycle in transdifferentiation of mononucleated cross striated muscle cells into smooth muscle and sensory cells in vitro. PMID- 2875464 TI - Molecular cloning of DNA complementary to bovine pituitary mRNA. PMID- 2875466 TI - Regulation in metagenic cnidarian planulae. PMID- 2875465 TI - Tubulin and associated proteins from developing brine shrimp, (Artemia). PMID- 2875467 TI - Endogenous low molecular weight factors, vitamin A and phorbol esters dramatically affect pattern formation and positional values in marine hydroids. PMID- 2875468 TI - Retinal development in the lizard Calotes versicolor: cell differentiation and glutamine synthetase activity. PMID- 2875469 TI - Alpha 2-adrenergic antagonists effect on amphetamine-induced behaviors. AB - The effects of alpha 2-adrenergic antagonists on amphetamine-induced locomotion and stereotypy were studied in mice. Six alpha 2-antagonists (i.e., yohimbine, rauwolscine, piperoxan, tolazoline, RX781094, and RS21361) selectively attenuated amphetamine-induced increases in locomotion at doses which did not effect amphetamine-induced stereotypies. Higher doses of the antagonists which attenuated baseline stereotypies also attenuated amphetamine-induced increases in stereotypies. The effect of the alpha 2-antagonists was qualitatively similar to that observed with the atypical antipsychotic clozapine. Furthermore, the in vivo relative potency of the alpha 2-antagonists in the present study was comparable to that reported in other studies. These results suggest that alpha 2-adrenergic receptors may modulate the effects of amphetamine on locomotion in mice. PMID- 2875470 TI - The neural substrates for the motor-activating properties of psychostimulants: a review of recent findings. AB - Several different classes of pharmacological agents produce syndromes of behavioral activation in humans and infrahumans. While many of these agents, including direct and indirect sympathomimetics, methylxanthines, opiates and several neuropeptides have very distinct neurochemical profiles, it is not clear whether their behavioral stimulant action results from their action on a common neural substrate, or instead from their action on parallel but separate activation "circuits.' Using photocell measurements of motor activity in rats, it has been possible to demonstrate that some agents with very distinct neurochemical identities act on common neural substrates to produce behavioral activation, while other agents act on completely distinct brain regions. Specifically, the locomotor-activating properties of direct and indirect sympathomimetics and opiates appear to result from their action within the basal ganglia, including the ventral striatum and globus pallidus, while the activating properties of caffeine and the neuropeptide, corticotropin releasing factor (CRF) appear to be independent of this circuitry. These findings suggest the presence of at least two separate neural systems capable of mediating behavioral activation. PMID- 2875471 TI - Two automated locomotor activity tests for dopamine autoreceptor agonists. AB - In the first test (exploratory activity), pretreated rats explored a novel environment in the dark. The potential autoreceptor agonists apomorphine HCl, N-n propylnorapomorphine (NPA), and N-n-propyl-3-(3-hydroxyphenyl)-piperidine (3-PPP) and its enantiomers decreased the total distance travelled while at the same time paradoxically increasing the number of discrete movements. This is a very different pattern from that of the typical antipsychotic drugs haloperidol HCl and chlorpromazine HCl, and the atypical antipsychotic drug clozapine, which also decreased the total distance travelled but decreased the number of movements. Both groups decreased the distance/movement. In the second test, rats were habituated to the monitors in the light and then treated with test drug and stimulant (d-amphetamine sulfate or apomorphine HCl). Apomorphine HCl, NPA, and (+)3-PPP antagonized amphetamine-stimulated locomotor behavior (total distance) without antagonizing apomorphine-stimulated behavior, suggesting a presynaptic dopamine autoreceptor agonism. EMD 23448 gave equivocal activity. On the other hand, haloperidol HCl, chlorpromazine HCl, and clozapine decreased both amphetamine- and apomorphine-stimulated behavior, suggesting a postsynaptic dopamine antagonism. 3-PPP and (-)3-PPP showed neither pattern in this test. PMID- 2875472 TI - Multivariate assessment of locomotor behavior: pharmacological and behavioral analyses. AB - A Behavioral Pattern Monitor (BPM) is described which is designed to assess the spatial and temporal sequences of the locomotor movements, investigatory holepokes, and rearings of rats. The system records these behavioral responses with 0.1 sec resolution in time and 1.5 inch resolution in space, and permanently stores all the resulting data. The sequences of these responses may then be displayed on a video terminal or on paper and are also available for the calculation of a variety of descriptive statistics. Studies are described in which rats were tested repeatedly without any pharmacological treatments or in single test sessions following the administration of saline or one of five stimulant drugs. A variety of descriptive measures of the temporal or spatial patterning of the animals' behavior are described and applied to the data resulting from the studies of the various stimulants. It is concluded that the combination of these measures enables distinctions to be made among these drugs which cannot be made on the basis of measures of the amount of locomotor activity. PMID- 2875473 TI - Altered neurobiological responses to acute immobilization in social-isolated mice. AB - Social isolation results in dynamic changes of neurobiological functions. The altered internal state of the CNS is reflected in changes in spontaneous behavior, changed responses to transmission-related substances and changed responsiveness to an additional impairment of normal relations between the organism and its environment. We analysed the influence of an acute 2-hour immobilization on such isolation-dependent changes. Whereas the susceptibility to pentetrazole-induced seizures increased continuously with lengthening of isolation and was not affected by the additional impairment, the responsiveness to transmission-related substances changed dynamically depending upon isolation induced alterations. An immobilization-induced increase in responsiveness to LSD and propranolol was demonstrable in grouped controls and after short-term isolation. The apomorphine stimulation during prolonged isolation experienced a down- and an upregulation which were repeated in a stronger manner by immobilization responses especially after long-term isolation. It is suggested that the dynamics of isolation-induced changes coincided with changed acute adaptive functions. PMID- 2875474 TI - Differential distribution of neurotransmitter amino acids from the limbic system of aggressive and non-aggressive bull strains. AB - The amino acid content of crude synaptosomal fractions from the limbic system and related CNS regions showed significant differences between the aggressive Spanish fighting-bull and the non-aggressive Friesan bull breeds. Neurotransmitter amino acids (glutamate, aspartate, GABA and glycine) were the most unequally distributed. A higher ratio of excitatory to inhibitory neurotransmitter amino acids was always found in all the CNS regions studied in the aggressive breed. The concentrations of five non-transmitter amino acids (threonine, alanine, serine, leucine and isoleucine) showed minor variations between both studied bull strains and cannot be ascribed to differences in central energy metabolism. The results are explained in terms of a possible relationship between the amino acid neurotransmitter levels and the innate aggressiveness of the Spanish fighting bull. PMID- 2875476 TI - Ambulation aid for nonweightbearing foot and ankle injuries. Suggestion from the field. PMID- 2875475 TI - Centrally-administered opioid selective agonists inhibit drinking in the rat. AB - The effects of intracerebroventricular injection of mu (morphine), kappa (dynorphin-(1-13), ethylketocyclazocine, and U50,488H), and delta ([D-Pen2, D Pen5]enkephalin) opioid agonists on water intake of 14 hr water deprived rats was studied. All agonists caused a dose related decrease in time spent drinking, with a rank order potency of dynorphin-(1-13) greater than morphine greater than ethylketocyclazocine greater than [D-Pen2, D-Pen5]enkephalin = U50, 488H. With the exception of morphine, all of the compounds increased the latency to begin drinking, but only at the highest doses tested. The rank order potency for this endpoint was dynorphin-(1-13) = ethylketocyclazocine greater than [D-Pen2, D Pen5]enkephalin greater than U50, 488H. The potent inhibition of drinking following centrally-given dynorphin-(1-13), at doses that did not affect the latency to begin drinking, supports a role for endogenous dynorphin in the homeostatic control of water balance. This function may not be primarily mediated through activation of a kappa opioid receptor since dynorphin-(1-13) was 80-230 times more potent than the selective kappa agonist, U50,488H or ethylketocyclazocine. PMID- 2875477 TI - [Dispensary treatment of endogenous psychoses from the viewpoint of the psychiatrist in ambulatory care]. AB - Reviewing the results of the observation of 72 patients suffering from endogenic psychoses during a period of 11 years the author tries to demonstrate the advantages of a basis-near, i.e. near to the places of living and employment, therapy for psychically sick persons. The necessity of long-term therapy is emphasized. PMID- 2875478 TI - Relationship of psychotic symptom clusters in schizophrenia to neuroleptic treatment and growth hormone response to apomorphine. AB - The authors propose an alternative model for relating clinically rated psychotic symptoms to biological measures in schizophrenic patients. They suggest that clinical presentation in schizophrenic patients comprises at least four distinct psychotic symptom clusters and that at most one or two of the symptom clusters are closely associated with central dopamine (DA) activity as measured by growth hormone (GH) response to apomorphine. Factor and cluster analytic techniques both identified the same four psychotic symptom clusters, three of which were similar to the major subtypes of schizophrenia: paranoid delusions (paranoid type), thought disorder (disorganized type), and catatonia (catatonic type). The fourth psychotic symptom cluster was auditory hallucinations, a prominent clinical feature of schizophrenia. The authors compared clinical symptom cluster scores to apomorphine-induced GH response by creating a new data set containing the output of the factor analysis of each patient's symptoms and GH response, and performing regression modeling of the patient's symptom cluster scores on GH response. Patients with elevated thought disorder cluster scores also had elevated GH responses to apomorphine, suggesting an association between thought disorder and central DA receptor supersensitivity. A fixed-dose neuroleptic trial showed that thought disorder and auditory hallucinations respond rapidly to treatment with a DA receptor blocker (haloperidol), while no significant effect on other symptom cluster scores occurred during the initial 2 weeks of treatment. These data suggest that two of the identified symptom clusters, thought disorder and auditory hallucinations, may be preferentially associated with central DA hyperactivity. PMID- 2875479 TI - Benzo-pyrones in the treatment of chronic schizophrenic diseases. AB - Sixteen chronic schizophrenic subjects were treated for 3 months each with either a benzo-pyrone (Paroven/Venoruton, Zyma) or a placebo in a randomized, double blind crossover trial. They continued to take their previous drug therapies. Therapeutic effects were measured by the Brief Psychiatric Rating Scale (BPRS), by self-assessment, and by assessment by a relative. Eleven patients completed the trial in relation to BPRS assessment. When on the active substance, as compared with the placebo, they showed a mean improvement of 27% (significant at the 1% level). Ten patients completed the trial in relation to the self and relative's assessments. There were improvements of 16% and 13%, respectively (significant at the 5% levels). Half the patients showed improvements on all the tests. Their improvements were 49%, 31%, and 21%, respectively. There was evidence that the active substance began to have an effect within 2 weeks. No side effects were observed with the active substance. PMID- 2875480 TI - Somatostatin and regulation of prolactin secretion. AB - In addition to its classical growth hormone (GH) inhibiting action, somatostatin (SRIF) inhibits prolactin (PRL) secretion in man and rat under specific endocrine conditions. Furthermore, SRIF counteracts the thyrotropin releasing hormone (TRH) and vasoactive intestinal peptide (VIP) stimulated prolactin release from rat adenohypophysis in vitro. Two criteria are needed to demonstrate a physiological role of SRIF in PRL control: specific receptors must be present on prolactin secreting cells, and antagonization of endogenous SRIF must affect PRL secretion in vitro. In fact [125I]N--Tyr--SRIF binds to membranes not only of human GH secreting adenomas, but also of prolactinomas. Specific binding characteristics are comparable in both cell types, but the density of sites in PRL-secreting adenomas is only one-quarter that in GH-secreting adenomas. In contrast, non-PRL secreting chromophobe adenomas are devoid of specific binding. On the other hand, administration of SRIF antisera (SRIF-AS) affects both GH and PRL secretion in starved rats (a model in which pulsatile GH secretion is abolished); a marked increase in PRL plasma levels occurs, but the needed SRIF-AS concentration is higher than that for GH disinhibition. This demonstrates that endogenous SRIF may exert a negative control over PRL secretion, although lactotroph cells appear less sensitive to SRIF than somatotrophs. Since the apparent affinity of SRIF binding sites is similar on both GH and PRL secreting cells, at least in human tumor tissues, a lower density of SRIF receptors on PRL cells could account for this reduced responsiveness. Alternatively, different coupling mechanisms may be involved in the two cell types. PMID- 2875481 TI - Serum levels and clinical response in long-term pharmacotherapy with zuclopenthixol decanoate. AB - Twenty-six patients diagnosed as chronic schizophrenics were given injections of zuclopenthixol decanoate (cis(Z)-clopenthixol decanoate) 200 mg every 3 weeks for at least 6 months. Before treatment and on each day of injection the patients' mental state was assessed by Brief Psychiatric Rating Scale (BPRS), 18 items. A registration of side effects and basal laboratory data was also performed. Blood samples were drawn on each day of injection before injection and 3-7 days after injection (time of maximum concentration). Neuroleptic activity, which was considered equivalent to the concentration of zuclopenthixol, was determined in serum by radio-receptor assay (RRA). Based on amelioration scores greater than or equal to 50% on the BPRS, 15 patients were characterized as responders and 11 as non-responders. The responder group showed a statistically significant reduction in BPRS score, whereas this was not the case for the non-responders. Apart from a few patients, the serum concentrations showed a low intra-individual variation, but a relatively high inter-individual variation. The responder group had a significantly higher mean pre-injection concentration than the non-responder group, whereas no significant difference was found in day 3-7 concentrations. The fluctuation of the serum concentration expressed as the ratio between maximum (days 3-7) and minimum (pre-inj.) was found to be significantly lower for responders than for non-responders. Thus although the present study did not demonstrate a clear relationship between serum level and clinical effect, it indicates that the best antipsychotic effect is obtained with a serum concentration which fluctuates only slightly (the ratio max/min concentration not exceeding 2.1). PMID- 2875483 TI - Subdural empyema--continuing diagnostic problems in the CT scan era. AB - Fourteen cases of subdural empyema seen in Oxford since the introduction of the CT scanner are reviewed; 11 were male and 12 survived. The clinical presentation was stereotyped and characterised by severe headache, fever and meningism followed after a few days by rapidly progressive drowsiness, focal signs, papilloedema and seizures. All had radiological evidence of paranasal sinus disease (particularly frontal) although this was not apparent clinically in the majority. Plain skull and sinus radiographs remain important early investigations. Over-reliance can be placed on the CT scan which initially may be normal or show only non-specific hemisphere swelling. Parafalcine collections are easily missed. The diagnosis of subdural empyema remains difficult and a high index of clinical suspicion is required. Outcome depends on prompt treatment with parenteral antibiotics and surgical drainage. PMID- 2875482 TI - The role of adenosinergic, GABAergic and benzodiazepine systems in hyperemotionality and ulcer formation in stressed rats. AB - The effects of benzodiazepines, GABA and adenosine on distress-induced hyperemotionality and gastric lesion formation were investigated in rats. Hyperemotionality such as struggling, vocalization and defecation evoked immediately after immobilization stress were attenuated by diazepam, adenosine or adenosine plus diazepam. Conversely, pretreatment with these drugs produced rapid and potent exacerbation of gastric lesions observed after 12 h of stress. The potent adenosine A1-receptor agonist N6-cyclohexyl adenosine (CHA) markedly inhibited the distress-evoked hyperemotional behaviors and potentiated the ulceration. gamma-Aminobutyric acid (GABA), muscimol, a GABA receptor agonist, and aminooxyacetic acid (AOAA), a GABA deaminase inhibitor, attenuated both stress-induced hyperemotionality and ulceration. The inhibitory effects of diazepam and GABA on hyperemotionality were reversed, respectively, by Ro15-1788, a benzodiazepine receptor antagonist, and bicuculline, a GABA receptor antagonist. The stimulatory effect of CHA on stress ulceration was potentiated by bicuculline but was not affected by Ro15-1788 or by picrotoxin, a chloride channel inhibitor. These results suggest that the mechanism involved in gastric lesion formation induced by immobilization stress may be different from that in hyperemotional behavior, and that the activation of GABAergic neurons may act as a central modulating factor in the hyperemotionality and ulceration induced by immobilization stress. PMID- 2875484 TI - Prediction of outcome in Graves' disease after carbimazole treatment. AB - In a prospective study to determine which factors would predict remission or relapse, 65 patients with hyperthyroid Graves' disease were treated for six months with a blocking replacement regimen of carbimazole, 40 mg daily, and triiodothyronine (T3). They were followed for one year after stopping treatment, by which time 32 (49 per cent) had relapsed. Although the treatment protocol, relapse rate and frequency of the HLA-DR3 antigen in this population were similar to those of a regionally separate Graves' population investigated previously, the predictive value of HLA-DR3 status together with thyroid stimulating antibody (TSAB) levels was strikingly different. In the present study there was no significantly abnormal distribution of any HLA antigen in the relapse group compared with those patients who achieved remission. Thyroid stimulating antibodies were detected in 62 patients (95 per cent) and fell significantly (p less than 0.05) after carbimazole treatment, irrespective of DR3 status or outcome; TSAB levels only became undetectable in nine patients (28 per cent) who subsequently relapsed and in nine patients (30 per cent) who maintained remission. T3-suppressed 20 min 123I uptake fell equally after treatment in the relapse and remission groups but continued to fall thereafter in the group which maintained remission. In these patients, 123I uptake was significantly lower at the end of the study period than at the end of treatment (p less than 0.05). Serum free T4 levels were higher before treatment in the patients who later relapsed than in those whose disease remitted (p less than 0.02). This proved the only significant marker associated with outcome but was of little predictive value in any patient. This study highlights the problem in predicting the outcome of antithyroid drug treatment, since even within the same country under similar conditions, divergent results have been obtained. It appears that the loci controlling the immune response in Graves' disease are likely to include genes lying outside the HLA-DR region. The results also suggest that the immunological effects of antithyroid drugs are maintained after stopping treatment in those patients whose disease remits. PMID- 2875485 TI - [Changes in the parameters of hepatic function in biliary lithiasis]. AB - Our study investigates liver involvement serum parameters in 71 subjects with cholelithiasis and choledocholithiasis, without primary liver diseases. As a control group 118 healthy subjects were studied. All patients have been examined for serum transaminases, alkaline phosphatase and gamma-glutamyl-transpeptidase, total bilirubin and for liver enlargement. The results point out the presence of increased alkaline phosphatase and gamma-glutamyl-transpeptidase levels in more than half examined patients, and in nearly half of those without hyperbilirubinemia. This fact confirms that the existence of biliary lithiasis itself (even if limited to gall-bladder, in absence of jaundice) may account for the occurrence of a subclinical cholestatic liver impairment, that should be carefully considered in long-term prognosis of these patients. PMID- 2875486 TI - [SEM study of the corrosion stability of solder in non-precious metal alloys]. PMID- 2875487 TI - [Fractures and luxations of the mid- and forefoot]. AB - These injuries are rare. Additional soft tissue lesions and multiple traumatic disorders of the foot are common, due to crush and traffic injuries. Surgery is needed for the reconstruction of the arch of the foot, its joints and soft tissue. The traumatic lesion of the soft tissue requires meticulous debridement, an exact reduction and osteosynthesis and primary wound closely by means of a synthetic material like Epigard. Providing reduction is adequate, it should be stabilised with percutaneous Kirschner wires. PMID- 2875488 TI - [X-ray examination of foot injuries]. AB - Fractures and luxations of the phalanges, metatarsus, tarsus and their joints are discussed. Correct radiological projections, knowledge of their pitfalls and a systematical interpretation are necessary for correct diagnosis. PMID- 2875489 TI - Biological correlates and detection of alcohol abuse and alcoholism. AB - There has been a continuing interest in the biological correlates of alcohol abuse and alcoholism, in part because structured clinical interviews and questionnaire-derived data are vulnerable to deliberate falsification and/or denial. Although alcoholics often report a history of specific complaints and diseases, many clinicians do not think that early alcohol abuse can be detected by evaluating this self-reported data. Although the search for a single biological marker for alcoholism has so far proved unsuccessful, several investigators have recently demonstrated that combinations of tests are more likely to identify alcoholics than single tests. Ideally, one would like to have a technique that would define when an individual is consuming too much alcohol, such that for one person it may be 4 drinks per day and for another it may be 6 drinks per day. Moreover, a clinically useful technique would identify binge drinkers as well as regular consumers, and would not be influenced by acute intoxication, age, other drug use, nonalcoholism-related medical conditions, or pathophysiology accompanying the alcohol withdrawal syndrome. PMID- 2875490 TI - Alcoholic organic brain disease: nosology and pathophysiologic mechanisms. AB - Study of alcoholic chronic organic brain syndrome may have applicability to the large population of alcoholics with less severe cerebral dysfunction. Brain impairment in alcoholics may be conceptualized as two clinically and neuropathologically distinguishable organic brain syndromes: alcohol amnestic disorder or Korsakoff's psychosis (KP) and alcoholic dementia. Alcoholic organic brain disease may result from two interacting pathophysiological processes: nutritional (thiamine) deficiency and ethanol neurotoxicity. Subcortical periventricular lesions associated with KP result primarily from thiamine deficiency, whereas ethanol neurotoxicity and various secondary effects of alcoholism may contribute to the cortical neuropathological changes associated with alcoholic dementia. These two patterns of brain damage may be differentiable in individual alcoholics using cognitive tests and other measures of CNS function and, therefore, allow selection of a treatment strategy based on pathophysiological considerations. Studies in animals and humans suggest that a genetic predisposition to thiamine deficiency may contribute to alcoholism associated dysfunction of brain and other organ systems and possibly have a causative role in the development of alcoholism. PMID- 2875491 TI - Role of pituitary and related neuropeptides in alcoholism and pharmacodependence. AB - Evidence is accumulating that hormonal systems present in the pituitary and the brain play a critical role in behavioral homeostase. The hormones and their fragments, called neuropeptides, produced by these systems modulate neurotransmitter activity and thereby control brain functions. Disturbances in this hormonal control may result in psychopathology, including addiction. Vasopressin and related peptides decrease under certain conditions addictive behavior of experimental animals and humans and brain reward. The pituitary and brain opioid peptides are candidates to play an essential role in reward processes and may be common factors in addiction to various psychoactive drugs, including heroin and alcohol, and to habits. Other pituitary hormones, like ACTH, gamma 2-MSH and prolactin have also been implicated in brain reward and drug addiction. It is postulated that disturbances in the hormonal and neuropeptide systems may lead to a state in which addiction behavior can easily be elicited and that the hormonal climate in the body may be of relevance for the individual susceptibility to addictive drugs. It is proposed to analyse the relation between hormonal systems and addictive behavior. PMID- 2875492 TI - [Regulation of degranulation and protein kinase C]. PMID- 2875493 TI - Different ionic requirements for somatostatin receptor subpopulations in the brain. AB - Two populations of brain somatostatin (SS) receptors, one with high affinity for the somatostatin octapeptide analogue SMS 201-995 (SS1 type) and one poorly sensitive to this analogue (SS2 type) have been characterised in regard to their ionic requirements using two radioligands, the iodinated Tyr3 derivative of the octapeptide SS analog SMS 201-995 and the iodinated [Tyr11]-SS. Specific binding of 125I-[Tyr11]-SS to rat cortex membrane homogenates can be increased by approximately 180% in presence of 5 mM Mg2+. The increase in number of binding sites seen by Mg2+ is not accompanied by a marked increase in affinity for SS but for SMS 201-995: the low affinity binding for SMS 201-995 seen in absence of Mg2+ is replaced in part by higher affinity binding in presence of these ions. SMS 201 995 sensitive SS1 receptor subpopulation measured with 125I-204-090, a specific ligand for SS1 subpopulation, is massively increased in presence of Mg2+. However, SMS 201-995 insensitive SS2 receptor population measured with 125I [Tyr11]-SS in presence of excess SMS 201-995 is unchanged in presence of Mg2+. The Mg2+-dependency can also be observed with autoradiography for extra cortical, i.e. hippocampal, brain SS receptors. 120 mM Na+ does not affect the total brain SS receptor population, but reduces the specific binding of SS1 receptors and increases that of SS2 receptors. Therefore, the rat brain, in particular the cortex, possesses a SMS 201-995-sensitive, Mg2+-dependent SS receptor subpopulation (SS1) as well as a SMS 201-995-insensitive, Mg2+-independent SS population (SS2). PMID- 2875494 TI - [Sympathetic block after plexus anesthesia. Comparison with stellate ganglion block]. AB - Plethysmographic measurements of the upper extremity were performed in ten patients after axillary plexus block and in eight patients after stellate ganglion block. Axillary plexus block was followed by a mean increase of 396% in arterial blood flow. After stellate ganglion block, the arterial blood flow increased by 232% (P less than or equal to 0.001) compared to the pre-block value. There was no change in venous capacity after either method. The results indicate that both blocks can alternatively be used, as they have the same effects regarding increased arterial flow and stable venous capacity. PMID- 2875495 TI - Calcium antagonists--drug interactions. AB - Evaluations of drug interactions should be done with caution. One needs to be aware of the reported interactions and apply the information on an individual basis. This review may therefore serve as a guide to the more common drug interactions and when drug therapy should be monitored closely in clinical practice. Major drug interactions with calcium antagonists are summarized in Table 2. PMID- 2875496 TI - Alpha- and beta-adrenoceptors in the female dog urethra. AB - The existence and subtypes of alpha- and beta-adrenoceptors in the female dog urethra were studied in vivo and in vitro by means of agonist and antagonist drugs. Noradrenaline, phenylephrine and B-HT 920, stimulants of alpha, alpha-1 and alpha-2 receptors respectively, caused an increase in the urethra tonicity. Thus indicating that the contractile activity is mediated by alpha-1 and alpha-2 adrenoceptors subtypes. On the other hand, the inhibitory urethral activity is under control of beta-adrenoceptors of beta-2 subtype, since the isoprenaline relaxing action is inhibited when beta-2 receptors are blocked, whilst this effect was not observed when beta-1 receptors were blocked. This fact was proved when beta-2 receptors were stimulated with salbutamol. PMID- 2875497 TI - Evidence that alpha-1-adrenergic stimuli specifically increase gluconeogenesis of the isolated proximal convoluted tubule in the rat. AB - Isolated kidney-cortical tubule suspensions and microdissected nephron segments from fed rats were used to study the action of catecholamines on gluconeogenesis. Gluconeogenesis from rat tubule suspension incubated with 5 mM pyruvate was stimulated maximally by 10(-5) M methoxamine, an alpha 1-selective agonist, and 10(-6) M noradrenaline by 29.2 +/- 5.2% (mean +/- SEM) and 32.6 +/- 2.9%, respectively. These effects were completely inhibited by 10(-7) M prazosin, a beta 1-selective antagonist. Yohimbine, an alpha 2-antagonist, also inhibited the effect, but only at a higher concentration (5 X 10(-5) M). Gluconeogenesis was not stimulated by isoproterenol, a alpha-agonist, at any concentrations between 10(-5) and 10(-7) M. With microdissected nephron segments, only the proximal tubule possessed gluconeogenic activity. Within the proximal tubule, the proximal convoluted tubule (PCT) revealed higher gluconeogenic activity than the proximal straight tubule (PST). Methoxamine at 10(-5) M stimulated gluconeogenesis in PCT, whereas in PST no increase of gluconeogenesis was observed. From these results, it can be concluded that an alpha 1-adrenergic agonist specifically stimulates renal gluconeogenesis in PCT, but not in PST. PMID- 2875498 TI - Effects of chronic ethanol administration on hepatic cholesterol and bile acid synthesis in relation to serum high density lipoprotein cholesterol in rats. AB - In ethanol-fed rats for 4 or 7 weeks, hepatic HMG-CoA reductase activity was significantly increased, and correlated positively with hepatic microsomal gamma GTP activity. By contrast, hepatic cholesterol 7 alpha-hydroxylase activity was decreased in these rats. The content of hepatic cholesterol and levels of serum cholesterol and HDL-cholesterol were significantly increased in these rats, correlating significantly with hepatic HMG-CoA reductase activity, but not with hepatic cholesterol 7 alpha-hydroxylase activity. These results suggest that the increase in serum levels of cholesterol and HDL-cholesterol by ethanol feeding is mainly regulated by the enhanced cholesterol synthesis in the liver. PMID- 2875499 TI - [The regimen of the diabetic, a dilemma]. PMID- 2875500 TI - [Clearance of immune complexes in lupus disease]. PMID- 2875502 TI - [Chronic appendicitis, a clinico-anatomical reality]. PMID- 2875501 TI - [Anti-inflammatory action of protein hydrolysates]. PMID- 2875503 TI - [Clinical aspects of primary hepatic neoplasms. A retrospective study over an 8 year period]. PMID- 2875504 TI - [Elements with prognostic value in the chronic evolution of viral hepatitis. Markers of the evolution]. PMID- 2875506 TI - [Duodenal ulcer in a painful episode or duodenal ulcer in a recurrent episode? (Opinions in formation)]. PMID- 2875507 TI - [Manifestations of rheumatism associated with hyperlipoproteinemia]. PMID- 2875505 TI - [Value of serum beta 2-microglobulin in diabetes mellitus]. PMID- 2875508 TI - [Case of massive hepatic steatosis secondary to thiamine abuse]. PMID- 2875509 TI - [Significance of antinuclear antibodies in rheumatology]. PMID- 2875510 TI - Bicuculline-induced alterations in neuronal responses to controlled tactile stimuli in the second somatosensory cortex of the cat: a microiontophoretic study. AB - Single-neuron activity (n = 29) was recorded from the second somatosensory cortex of cats, and the effect of glutamate, gamma-amino-butyric acid (GABA), and bicuculline methiodide (BMI) on spontaneous and stimulus-induced responses were analyzed. Iontophoresis of glutamate produced dose-dependent increases in spontaneous activity, whereas GABA suppressed both spontaneous and glutamate induced activity. Neuronal responses elicited by cutaneous stimuli were also inhibited by GABA in a dose-dependent fashion; current levels needed to produce at least a 25-50% decrease in stimulus-evoked activity ranged from 5 to 100 nA, with a mean of about 45 nA. Iontophoresis of BMI (10-75 nA) effectively antagonized GABA-induced inhibition of stimulus-evoked responses without altering spontaneous activity. Furthermore, BMI increased the magnitude of responses produced by ramp stimuli and caused a several-fold increase in receptive field size. For neurons responsive to sinusoidal stimulation, BMI caused an increase in the frequency-following probability at preferred frequencies, but failed to alter the response to nonpreferred frequencies. These results suggest that GABA-ergic circuits may limit response magnitude but not the submodality properties of somatosensory cortical neurons. PMID- 2875511 TI - [Coronary surgery]. PMID- 2875512 TI - A comparison of cultured aortic smooth muscle cells from different sources: are they all the same? PMID- 2875513 TI - [Objectives of scientific research in the field of rheumatology in the RSFSR in the light of the resolutions of the 27th CPSU Congress]. PMID- 2875514 TI - [Research on helminth eggs and protozoan cysts on money]. PMID- 2875515 TI - Beta-adrenergic agonists inhibit gastric acid and pepsin secretion through somatostatin release in dogs. AB - The purpose of the present study was to evaluate whether the inhibitory effects of beta-adrenergic agonists on gastric secretory activity in vivo could be mediated through a local release of somatostatin. The gastric secretion was measured during continuous stimulation with pentagastrin (1 microgram/kg/h). The infusion of isoprenaline (beta 1 + beta 2), salmefamol (beta 2), and somatostatin produced inhibitory effects on both acid and pepsin secretion. The reaction patterns were similar for isoprenaline and somatostatin, whereas salmefamol induced an inhibition of longer duration and with dissimilar dose-response kinetics. The gastric somatostatin release was significantly increased after infusion of both beta-adrenergic agonists and somatostatin, with patterns similar to those obtained for the secretory inhibition. There was a significant correlation between the somatostatin release and the acid and pepsin secretion during infusion of the secretory inhibitors but not in the control state. This study shows that beta-adrenergic agonists have inhibitory effects on gastric secretion in vivo similar to those of somatostatin. Both somatostatin and the beta-adrenergic agonists stimulated the release of somatostatin from the gastric mucosa. beta-Adrenergic antagonists were without effects. Somatostatin thereby fulfils the requirements for an endogenous mediator of the beta-adrenergic inhibition. PMID- 2875516 TI - Effect of serotonin on bethanechol-stimulated gastric pepsin secretion in dogs. AB - The effect of serotonin on bethanechol-stimulated gastric pepsin secretion was evaluated with regard to dose-response kinetics and receptor mediation. A low dose of exogenous serotonin produced a stimulation (0.5 microgram/kg/min), whereas inhibition was found for higher doses (5-10 micrograms/kg/min). The inhibition was non-competitive and could be significantly counteracted by beta adrenergic blocking drugs. This study confirms results obtained during pentagastrin stimulation and supports the concept that serotonin acts via sympathetic nerves to release noradrenaline. PMID- 2875517 TI - Effect of somatostatin on histamine-stimulated gastric acid and pepsin secretion in dogs. AB - The purpose of the present study was to evaluate the effect of somatostatin on gastric acid secretion and pepsin secretion in conscious dogs with gastric fistula. Infusion of histamine stimulated dose-dependently the acid secretion, whereas pepsin secretion was decreased by the high doses of histamine. Somatostatin inhibited dose-dependently the stimulated acid secretion but only with a maximum of 40%. The pepsin secretion was inhibited by somatostatin dose dependently and with a higher potency. The acid inhibition was of a competitive type and prostaglandin-independent. PMID- 2875518 TI - Steady-state kinetics of 5-aminosalicylic acid and sulfapyridine during sulfasalazine prophylaxis in ulcerative colitis. AB - Fifteen adult and 19 pediatric outpatients with ulcerative colitis were studied to determine the steady-state kinetics of 5-aminosalicylic acid (5-ASA) released from salazosulfapyridine (SASP). Results of excretion in adults (mean 24-h recovery of 5-ASA, 21% in urine and 57% in feces) were compatible with those of healthy volunteers. Since mean SASP dose/kg body weight (about 50 mg/kg) and compliance (reflected in sulfapyridine recovery) were equal in adults and pediatric patients, the results of the patient groups could be compared. Near complete azo reduction of SASP occurs in children. Absorption and excretion of 5 ASA and metabolism to acetyl-5-ASA did not differ statistically between pediatric and adult patients. However, the fecal excretion of the drug and its metabolites was significantly lower in young patients, although fecal concentrations were the same. The present results demonstrate that SASP is an excellent sustained-release drug for the delivery of 5-ASA to the lower part of the bowel system and provide a reference for comparison of 5-ASA kinetics after treatment with newer 5-ASA preparations. PMID- 2875519 TI - Bacterial adherence in urinary tract infections caused by Escherichia coli. PMID- 2875521 TI - Molecular structure and absolute configuration of suberogorgin. AB - In the present paper it is reported that the molecular structure and absolute configuration of poisonous suberogorgin are determined by using X-ray diffraction method. The crystal of suberogorgin belongs to orthogonal system with space group D4(2)-P2(1)2(1)2(1). The crystallographic parameters are: a = 16.135A, b = 13.189A, c = 12.901A, Z = 8. The initial model of the crystal structure was solved by the direct method. The refinement of the structure parameters was carried out by using the least square method and led to a final R-factor of 0.056. In accordance with the molecular structure of suberogorgin mentioned above, the solvent effect of NMR has been further discussed and the relationship between the molecular structure of suberogorgin and its toxicity has also been preliminarily investigated. PMID- 2875520 TI - [Enteropathogens in travellers returning from the tropics]. AB - Diarrhea is not only the most common health hazard during travel in the tropics but also the most frequent condition which prompts returning travellers to see a physician. The prevalence of bacterial and parasitic enteropathogens in people attending our outpatient department after returning from the tropics has been studied and the laboratory results of stool examinations have been compared with clinical symptoms. Of the 173 persons enrolled, 19 (11%) harboured bacterial pathogens and pathogenic protozoans (Giardia lamblia and Entamoeba histolytica) were found in 26 (15%). The data of 156 patients were evaluated. Enteropathogenic bacteria and/or protozoa were found in 29 (46%) of the 63 patients presenting with diarrhea at the time of investigation. In contrast, 10 (11%) of the 93 asymptomatic subjects had enteropathogenic organisms in the feces (p less than 0.01). The results appear to confirm that bacteriological stool examinations of travellers returning from the tropics without diarrhea are not usually indicated, even if a history of transient travellers' diarrhea is reported. Parasitological investigations are justified in this group only if asymptomatic carriage of Giardia or E. histolytica is considered an indication for specific treatment. PMID- 2875522 TI - Neurons containing NADPH-diaphorase are selectively resistant to quinolinate toxicity. AB - Exposure of cultures of cortical cells from mouse to either of the endogenous excitatory neurotoxins quinolinate or glutamate resulted in widespread neuronal destruction; but only in the cultures exposed to quinolinate, an N-methyl-D aspartate agonist, was there a striking preservation of the subpopulation of neurons containing the enzyme nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). Further investigation revealed that neurons containing NADPH-d were also resistant to the toxicity of N-methyl-D-aspartate itself but were selectively vulnerable to the toxicity of either kainate or quisqualate. Thus, neurons containing NADPH-d may have an unusual distribution of receptors for excitatory amino acids, with a relative lack of N-methyl-D-aspartate receptors and a relative preponderance of kainate or quisqualate receptors. Since selective sparing of neurons containing NADPH-d is a hallmark of Huntington's disease, the results support the hypothesis that the disease may be caused by excess exposure to quinolinate or some other endogenous N-methyl-D-aspartate agonist. PMID- 2875523 TI - Gene splicing dominates review of weapons pact. PMID- 2875524 TI - [Physiopathology of Parkinson's disease]. PMID- 2875525 TI - [Glifanan]. PMID- 2875526 TI - [Tercian]. PMID- 2875527 TI - [Pulmonary hypertension in chronic obstructive lung diseases]. PMID- 2875528 TI - [Tooth and jaw injuries in bicycle accidents]. PMID- 2875529 TI - Influence of the nature and the dose of the initiator on the development of premalignant and malignant lesions in rat hepatocarcinogenesis. AB - Using a triphasic protocol recently described to induce malignant tumors in rat liver, the question has been asked whether both the nature and the dose of the initiator influence the carcinogenic process. Two nitrosamines (diethylnitrosamine DEN and N-nitrosomorpholine NNM) have been used to initiate that process. With regard to the premalignant stages appearing in the liver up to 19 weeks after initiation, there is a dose-dependent relationship between the dose of initiator and both the percentage of the parenchyma occupied by and the number of GGT+ lesions. DEN is always more potent than equivalent doses of NNM. With regard to malignant tumors appearing within the period of observation (up to 44 weeks), the two highest doses (100 and 200 mg/kg) of DEN appear to be the only carcinogenic treatments. Cancer incidence (percentage of rats bearing histologically characterized malignant tumor) is the same after both treatments, but the tumor yield (number of tumors per rat bearing macroscopic tumors) is higher (+/- 2X) after 200 mg/kg than after 100 mg/kg. PMID- 2875531 TI - Agent Orange and risks to reproduction: the limits of epidemiology. PMID- 2875530 TI - Effect of prenatal imipramine exposure on development of the postnatal rat heart and brain. AB - Imipramine (IMI) was administered s.c. at 0, 5, or 10 mg/kg/day to pregnant rats on gestation days 8-20 to assess possible alterations in postnatal heart and brain development. Maternal weight gain was significantly reduced in a dose response manner, but litter size and pup weight on postnatal day (PND) 1 were unaffected. On PND 1, litters were culled to 10 pups for analysis on PNDs 4/5, 7/8, 14/15, and 21/22. Pup body weight was not affected at any age measured, but heart weight was significantly reduced at 10 mg/kg IMI on PNDs 4/5 and 7/8. Brain weight was increased in a dose-related pattern on PNDs 4/5 and 7/8 and was significantly higher at 5 mg/kg IMI on PND 14/15. No significant effect was observed in heart or brain protein and DNA content or in cardiac beta-adrenergic receptor concentration. Prenatal IMI exposure had no effect on basal cardiac ornithine decarboxylase (ODC), an enzyme associated with growth and development, but basal brain ODC was lower at 5 mg/kg IMI at all ages measured. Cardiac ODC stimulation by insulin was unaffected by prenatal exposure to IMI, but isoproterenol-stimulated ODC was increased on PND 21/22 at 5 mg/kg IMI. In conclusion, the IMI-related changes in several parameters suggest that when maternal IMI treatment is used, alterations in postnatal heart and brain development must be considered as possible outcomes. PMID- 2875532 TI - Deoxycytidine reverses inhibition of morphogenesis by thymidine in young chick blastoderm. AB - Exogenous thymidine affects morphogenesis of the early chick blastoderm possibly by depleting the deoxycytidine triphosphate pool. The aim of this study is to determine whether the inhibitory action of thymidine on early chick blastoderm morphogenesis is alleviated by the removal of thymidine and/or treatment with deoxycytidine. Chick blastoderms at the full hypoblast stage develop abnormally in egg albumen containing 1.23 X 10(-3) M thymidine. Development is normal when deoxycytidine is included simultaneously in the culture medium with thymidine at equimolar concentrations. Blastoderms were cultured in egg albumen containing 15 microCi/ml thymidine [methyl-3H] or 10 microCi/ml deoxycytidine [5-3H], and 1.2 X 10(-3) M 2'-deoxycytidine or 1.23 X 10(-3) M thymidine, respectively. The culture was interrupted at timed intervals, and the amount of radioactivity associated with DNA was determined. Exogenous deoxycytidine in the culture medium caused a noticeable increase in the incorporation of 3H-thymidine, while exogenous thymidine markedly inhibited the uptake and incorporation of 3H-deoxycytidine into DNA of blastoderms. Thymidine does not inhibit the expansion of blastoderm, the migration of cells for formation of the primitive streak (PS), and the induction of axial tissues, but it interferes with the organization of these tissues to form the embryonic axis. Blastoderms show slight signs of recovery when thymidine is removed. Deoxycytidine counteracts the action of thymidine and seems to be a rate-limiting factor in normal differentiation of the early chick blastoderm. PMID- 2875533 TI - Endotoxin-induced hyperthermia in pregnant golden hamsters. AB - The degree of elevation and the duration of induced fever following endotoxin treatment of pregnant golden hamsters were examined. A radiothermistor was surgically implanted in the abdomen of each animal on day 6 of pregnancy. The animals were intravenously treated with a bolus injection of saline or endotoxin (1, 10, 20, or 200 micrograms/kg) on the morning of day 8 of gestation. Abdominal temperatures were monitored at 15-minute intervals on days 8 and 9 and at 1-hour intervals on days 10 through 14 of gestation. The mean temperature of the saline treated control animals was 37.2 degrees C with a range from 36.5 to 38.2 degrees C. The total number of viable fetuses, and the mean fetal weight of the 1 microgram/kg group were not significantly different from those of the saline controls, although a statistically significant monophasic temperature elevation did occur between 3 and 9 hr post-treatment. Three of seven females that received 10 micrograms/kg had viable litters and exhibited a monophasic fever. The remaining four animals exhibited a biphasic fever and total resorption of all implanted fetuses. The first phase began 2.5 hr post-treatment and lasted for 3-6 hr. The second phase began 12-15 hr post-treatment and lasted for 15 to 25 hr. All animals receiving 20 or 200 micrograms/kg demonstrated similar multiple temperature elevations. Treatment of animals with greater than 20 micrograms/kg resulted in total resorption of all implanted fetuses and maternal weight loss. Nonpregnant females treated with 20 micrograms/kg of endotoxin exhibited a biphasic temperature elevation; thus the second phase of the fever response can not be attributed to embryo death and resorption. PMID- 2875534 TI - Mutagenic and cytotoxic potencies of a series of anthracycline derivatives as measured by His+ reversion, 8-azaguanine resistance and direct plating cytotoxicity tests in Salmonella typhimurium. AB - His+ reversion at multiple his- loci, 8-azaguanine resistance, and a previously reported direct plating cytotoxicity test were used to measure the genotoxic potencies of a series of anthracycline derivatives in Salmonella typhimurium. N demethylated amino sugar monosaccharide anthracyclines reverted most his- tester strains and were positive with 8-azaguanine selection. Reversion of strain TA98 was the most sensitive end point for measuring the mutagenic activity of the N demethylated anthracyclines. N,N-dimethyl amino sugar derivatives of Adriamycin and daunomycin were negative as measured by His+ reversion in tester strain TA98, but generated positive responses in tester strain TA102 that were equal to or greater than those of the demethylated parent compounds. Similarly, N,N-dimethyl amino sugar derivatives of pyrromycinone and 1-deoxypyrromycinone had no mutagenic activity as measured by His+ reversion except in tester strains TA102 and TA104. These later compounds also gave positive responses with 8-azaguanine selection. In view of these results, the importance of amino sugar dialkylation and anthracycline mechanisms of mutagenesis are discussed. PMID- 2875535 TI - Microsomal mediated embryo toxicity due to superoxide radicals. AB - The transfer of toxic substances to the developing fetus with deleterious results on pregnancy outcome is well known. It is now clear that the preimplantation period of development is susceptible to such exposure. This early developmental period is a time of critical genetic determination and a period during which much membrane synthesis is occurring. Since disruption of membrane formation might be important in the disorganization of embryos, microsomal protein-mediated toxicity in mouse blastocysts was explored. The embryos were shown to be completely disorganized by exposure to induced microsomal proteins in the presence of NADPH. All of the embryos exposed died within 18 hr. The effect was completely eliminated by boiling the microsomes or by removal of NADPH. Decreasing toxicity of the exposure could be achieved by adding butyl hydroxy toluene, an antioxidant. An amount of 0.001 mg/ml resulted in 100% viability in the presence of microsomes and cofactors after 2 hr (33% viability after 18 hr); however BHT resulted in its own toxicity at 0.025 mg/ml. Superoxide dismutase, an enzyme that removes superoxide radicals by dismutation, was completely protective with as little as 0.6 IU of enzyme added to the incubation mixture. PMID- 2875536 TI - Uptake by cells of nucleic acids promoted by compounds sharing the pleiotropic effects of poly(ethylene glycol). AB - Poly(ethylene glycol) (PEG) is a member of a group of membrane active compounds that have pleiotropic effects on cells, eg, promotion of cell fusion, induction of erythroleukemia cell differentiation, and protection of cells from freezing damage. Since PEG has recently been shown to be an efficient promoter of genetic transformation in bacteria, yeast, and mammalian cells, studies were carried out to determine whether other PEG-related compounds could also promote genetic transformation. In this study, 24 compounds, which behave like PEG in other biological systems, are shown to promote transfection of human cells with isolated poliovirus RNA. That PEG and other commercially important compounds promote transfection indicates that such compounds may represent a biohazard to man. PMID- 2875537 TI - Twin study methodology and variability in xenobiotic placental metabolism. AB - The present study assesses the contribution of genetic and environmental factors to variability in placental aryl hydrocarbon hydroxylase and glutathione transferase activities using twin study methodology. Twin placentas were collected at the time of delivery. The placenta, except for a single layer of maternal decidua, consists of fetal tissue exhibiting fetal genotype. Microsomal and cytosolic fractions were prepared under stringent protocols to prevent enzyme activity loss. There were two monozygotic-monochorionic pairs, five monozygotic dichorionic pairs, and 21 dizygotic-dichorionic pairs that showed measurable aryl hydrocarbon hydroxylase activity using the direct fluorometric assay. Most of the mothers were smokers. Aryl hydrocarbon hydroxylase activity was measured with two different substrates, benzo(a)pyrene and 7-ethoxyresorufin. Glutathione transferase activity was measured using glutathione and 1-chloro-2,4 dinitrobenzene as substrates for a spectrophotometric assay that follows the conversion of the aromatic substrate. Twin pair similarity was calculated with intraclass correlation coefficients. There is a high correlation between the activities of the two aryl hydrocarbon hydroxylase substrates (r = .814), but no correlation between aryl hydrocarbon hydroxylase and glutathione transferase activity levels. There is little evidence of genetic variability underlying the variation in the enzyme activities because monozygotic-dichorionic twins are no more similar to each other for the three substrate activities than are the dizygotic twins. To delineate the prenatal environmental influences on placental enzyme variability, dichorionic placentation was subdivided further into contiguous and noncontiguous placental position. Lower intraclass correlation coefficients are obtained for the dizygotic twins whose placentas were noncontiguous compared with dizygotic twins with contiguous placentas. The results suggest that most of the variability seen in these placental enzyme systems is due to environmental differences within uteri, rather than genetic variability in the population. This does not negate the possibility that between pair, or population, variability may have a genetic component, because even dizygotic twins share a large proportion of their genes. This study points out that a significantly variable environment exists within the human uterus. PMID- 2875538 TI - Antimutagenic effects of natural and synthetic hormonal steroids. AB - Among the steroid molecules, bile acids have been shown to have either a co- or an antimutagenic activity toward various direct and indirect acting mutagens in the Ames test. The present report extends such observations to other steroids having hormonal activity. The main effect of the active hormones is an inhibition of the genotoxicity of both direct and indirect acting mutagens. This effect is strictly structure-related. Moreover, both ethinyl oestradiol and mestranol, which are synthetic derivatives of beta-oestradiol largely used in contraceptive pills, are strong inhibitors of the mutagenicity, acting at nanomolar concentrations. The present article emphasizes the possible role of compounds with steroid structure as modulators of genotoxicity. PMID- 2875539 TI - Sublethal pH decrease may cause genetic damage to eukaryotic cell: a study on sea urchins and Salmonella typhimurium. AB - Further evidence is reported here of genetic and developmental damage that can be induced by a sublethal pH decrease. The effects of three inorganic acids (HCl, H2SO4, and H3PO4) on embryos and sperm from the sea urchins Sphaerechinus granularis and Paracentrotus lividus were evaluated. In addition, acidification of the medium was tested for spontaneous reversion to His+ prototrophy in Salmonella typhimurium (strains TA97, TA98, TA100, TA102, TA1535) up to toxic levels, by both liquid incubation and agar plate incorporation. The induction of developmental and mitotic abnormalities in S. granularis confirmed our previous observations on P. lividus. Embryotoxicity was exerted in S. granularis more severely by H3PO4 than by HCl or H2SO4 (pH 7 to 6), while the induction of mitotic abnormalities appeared at a pH of less than or equal to 6.5 irrespective of the acids used. By suspending S. granularis or P. lividus sperm in acidified filtered seawater (fsw) and then inseminating the eggs in natural fsw (pH = 8.0), the offspring showed developmental and mitotic abnormalities. Low-pH-induced spermiotoxicity was ruled out in our experiments, since fertilization success of acid-exposed sperm was actually enhanced, as compared to sperm suspended in untreated fsw. The exposure of S. typhimurium to different pH's (ranging from 4 to 9) invariably failed to induce any changes in reversion rates, regardless of the acids (or alkali) being used. These results suggest that extracellular acidification may cause sublethal damage that in turn leads to an impairment of mitotic activity and cell differentiation. PMID- 2875540 TI - Genetic variation in the susceptibility to mercury and other metal compounds in Drosophila melanogaster. AB - The tolerance of Drosophila melanogaster to heavy metal compounds was investigated with special emphasis on methylmercury. A pronounced variation in tolerance to CH3HgOH, HgCl2, (C2H5)3PbCl, (CH3)3SnCl, and CdCl2 was recorded between 12 wild-type strains. After ranking the tolerance of the strains with respect to the five compounds rank correlations for experiments within and between compounds were calculated. The results showed a high degree of correlation within compounds but no unequivocal indication of a correlation between compounds, indicating that different mechanisms of genetic control for tolerance were operating for the five compounds. Rank correlations for experiments with 12 different mercury, lead, tin, and cadmium compounds and the same 12 wild-type strains only indicated one significant correlated response, between tripropyltin and tributyltin. A selection experiment for tolerance to methylmercury was performed with a foundation population, synthesized from four wild-type strains, showing a high initial tolerance. One control and two levels of treatment doses were used. A distinct selection response was obtained and a high tolerance was reached particularly for the high-dose selection line after 12 generations, when the experiment ended. Genetic analysis of the tolerance indicated a dominant and polygenic inheritance. Investigation of the uptake and excretion of CH3Hg203OH showed that the level of tolerance to methylmercury was correlated with the uptake of the mercury but apparently not with the rate of excretion. Cystein increased the susceptibility to methylmercury. Inorganic mercury and trimethyl lead exhibited a synergistic toxic effect, evidently as the result of an in vitro transmethylation of mercury. A high somatic susceptibility to methylmercury also applied to the induction of nondisjunction and sex-linked recessive lethals. PMID- 2875541 TI - Quantitative analysis of the metabolism of benzo(a)pyrene by transformable C3H10T1/2CL8 mouse embryo fibroblasts. AB - The metabolism of benzo(a)pyrene [B(a)P] to organic soluble and water soluble metabolites by transformable C3H10T1/2CL8 mouse embryo fibroblasts was studied as a function of time, B(a)P concentration, and cell density. The total formation of organic-soluble and water-soluble metabolites increased with incubation time from 4 to 48 h and with B(a)P concentration from 4 to 40 microM. As cell density increased, the metabolic rate decreased for organic-soluble and water-soluble products between 6,300 and 54,000 cells/cm2 probably due to decreases in B(a)P concentrations to values below saturation. Specific organic-soluble metabolites identified were B(a)P-pre-9,10-diols, B(a)P-9,10-diol, B(a)P-7,8-diol, B(a)P-3,6 quinone, B(a)P-3-phenol, and B(a)P-9-phenol. Water-soluble metabolites were subjected to enzymatic hydrolysis with beta-glucuronidase and aryl sulfatase to identify specific conjugated products. The sulfate conjugated metabolites identified were B(a)P-7,8-diol, B(a)P-pre-9,10-diols, B(a)P-9,10-diol, and B(a)P 3,6-quinone. The beta-glucuronic acid metabolites identified were B(a)P-pre-9,10 diols, B(a)P-3,6-quinone, and B(a)P-3-phenol. Patterns of metabolite formation rates are discussed as to their possible effect on morphological transformation rates in C3H10T1/2 cells with respect to incubation time and cell density. PMID- 2875543 TI - The effects of maternal murine cytomegalovirus infection on the mouse conceptus at different gestational stages. AB - The effects of murine cytomegalovirus (MCMV) on the prenatal development of the CD-1 mouse were investigated. Two sets of experiments were performed. In the first, mice were inoculated with different doses of MCMV on gestational day 7, and in the second, pregnant animals were inoculated with a subacute injection dose at different gestational stages. The effects of maternal infection on pregnancy in terms of maternal sickness, embryo lethality, date of parturition, litter size, postnatal death, and pups' body weight on d 1 and d 3 postpartum were investigated. High-dose MCMV infection on d 7 of pregnancy resulted in a significant increase in early embryo resorption and also in a reduction of the neonatal body weight of surviving pups. Two gestational stages were identified as being especially susceptible to MCMV infection. Most embryonic death as indicated by resorption rates was found after treatment on d 9, whereas perinatal death was most frequent when treatment was done on d 13 of gestation. Still births and neonatal death within 24 h of birth were found commonly in this latter group, which also showed the most pronounced growth retardation. The phenomenon of delay in time of parturition was noted and found to be most significant in groups of animals that were inoculated on d 3 or d 13. This investigation suggests that the effects of MCMV on the CD-1 mouse vary greatly with the age of the embryo and the course of the infection. PMID- 2875542 TI - Comparative in vivo and in vitro sister chromatid exchange studies in Chinese hamster bone marrow and spleen cells. AB - The sister chromatid exchange (SCE) assay in bone marrow and spleen cells of Chinese hamsters was used to evaluate the differences between in vivo and in vivo/in vitro (exposure of animals to chemical followed by culturing of cells) conditions. Cyclophosphamide, a mutagenic carcinogen, caused dose-related SCEs both in vivo and in vivo/in vitro. In the in vivo group, both bone marrow and spleen cells showed approximately a five-fold increase in SCEs over controls following 40 mg cyclophosphamide/kg treatment. The same dose, under in vivo/in vitro conditions, caused about three- and six-fold increases in SCEs over controls in bone marrow and spleen cells, respectively. While the extent of cyclophosphamide-induced SCEs (after subtraction of baseline level) in bone marrow is approximately the same under both conditions, the response was significantly higher in spleen cells in vivo/in vitro than in vivo. Under in vitro conditions, treatment of bone marrow and spleen primary cell cultures with a direct acting mutagen, trinitrofluorenone, caused significant dose-related increases in SCEs in both cell types in an equivalent manner. The replicative indices under these experimental conditions remained almost the same. Thus, this study indicates the potential usefulness of Chinese hamster bone marrow and spleen cells for in vivo and in vitro comparative studies with the same tissue to better assess the genotoxic hazard of chemicals. PMID- 2875544 TI - [Soria Moria--a dream becomes reality]. PMID- 2875545 TI - [Crotamiton (Eurax) as a mosquito repellent]. PMID- 2875546 TI - Evaluation of N-isopropyl-[125I]p-iodoamphetamine affinity sites in rat brain by autoradiography. AB - Affinity sites of N-isopropyl-[125I]p-iodoamphetamine (IMP) were studied in rat brain employing in vitro technique of receptor autoradiography. High degrees of IMP accumulation were observed in almost regions of white matter and some of gray matter. Phenethylamine, glutamic acid and serotonin suppressed IMP accumulation in all brain regions, in cerebral cortex and in hypothalamus, respectively. These results indicated that IMP was accumulated mainly due to its physicochemical property of lipophilicity and might have some interactions with neurotransmitter receptors. PMID- 2875547 TI - Treatment of reflux esophagitis with histamine H2-receptor antagonists. PMID- 2875548 TI - Pharmacological effects of various venoms on cutaneous capillary leakage. AB - Studies to counteract the cutaneous vasopermeability actions of a wasp (Vespa orientalis), an anemone (Bolocera tuediae) and three jellyfish (Chironex fleckeri, Chrysaora quinquecirrha and Physalia physalis) venoms were conducted by using various pharmacological antagonists. Piripost (a leukotriene inhibitor) reduced vasopermeability if administered 5 min prior to challenge with the jellyfish venoms. Methysergide counteracted the vasopermeability of three of four coelenterate venoms, whereas indomethacin was effective against capillary leakage induced by Chironex venom. These studies indicate that anti-dermonecrotic therapy against various venoms will have to be species-specific. PMID- 2875549 TI - A stress-diathesis theory of suicide. PMID- 2875550 TI - Histocompatibility loci associated with lymphocyte alloantigenic loci. PMID- 2875552 TI - [Implementation of the resolutions of the 27th Congress of the CPSU]. PMID- 2875551 TI - [Status after 5-year hormonal treatment (LH-RH) for non-descended testis]. PMID- 2875553 TI - [The 27th Congress of the CPSU--the congress of strategic decisions]. PMID- 2875554 TI - Annulate lamellae of the pancreatic exocrine cells in starved rats. AB - The ultrastructure of annulate lamellae in the pancreatic exocrine cells of rats starved for 3-42 days was studied. Annulate lamellae were rarely encountered in the pancreatic exocrine cells of control rats, but their incidence and size of stack was increased in those of starved rats depending on the duration of starvation, despite marked ultrastructural changes in these cells. Annulate lamellae were located in the para- or infranuclear cytoplasm of the cells and most of them were continuous with the relative normal rough endoplasmic reticulum. A close apposition in parallel was often found between the annulate lamellae and the outer nuclear envelope and occasionally pores in line with those of the nuclear membrane were observed in the lamellae of rough endoplasmic reticulum in 35- and 42-day-starved rats. An unequivocal continuity between the annulate lamellae and the nucleus and/or rough endoplasmic reticulum in pancreatic exocrine cells might be related to their origin and function. PMID- 2875555 TI - Accumulation of mercury in the anterior pituitary of rats following oral or intraperitoneal administration of methyl mercury. AB - A sensitive histochemical technique has been used to visualize the ultrastructural localization of mercury in the anterior pituitary of rats which have been exposed to methyl mercury. After administration of methyl mercury in the drinking water (20 mg X l-1 methyl mercury in distilled water) or intraperitoneally (daily dose 100 ug or 200 ug methyl mercury) intracellular accumulations of mercury were found in the lysosomes and granules of secretory cells (somatotrophs, thyrotrophs and corticotrophs). In non-secretory cells (follicular cell and marginal layer cells) mercury deposits were found in lysosomes. In orally treated rats, the number of mercury deposits increased significantly with time up to day 21. In rats exposed intraperitoneally, a continuous increase was seen in intracellular mercury accumulation. Apart from vacuolation of lysosomes, no structural damage was observed in the cells containing mercury. PMID- 2875556 TI - Inhibitory effect of an oxygenated cholesterol on the induction and progression of DMBA-induced mammary carcinomas in the rat. AB - In vivo studies on the effect of two stereoisomeric 7,22-dihydroxycholesterols on tumor development were conducted in the Charles Huggins animal cancer model (DMBA induced mammary cancer in the Sprague-Dawley female rat). Three groups of DMBA treated animals were fed a 9:1 mixture of (22R)-cholest-5-ene-3 beta,7 beta,22 triol and (22R)-cholest-5-ene-3 beta,7 alpha,22-triol in the drinking water in a calculated dose of 250 micrograms per animal per day. One group (A) received the sterols throughout the experimental period of 35 weeks, another group (B) during the first 12 weeks only, and a third group (C) only during weeks 13 through 35 after DMBA injection. Tumor rates and tumor yields were calculated, and statistical assessment by accepted methods demonstrated a very significant inhibitory effect on tumor development in Groups A and B, as compared with Group C. The results indicate a growth-inhibitory effect during the induction period of carcinoma development. The influence on neoplastic growth of (22R)-cholest-5-ene 3 beta,7 alpha,22-triol, (22R)-cholest-5-ene-3 beta,7 beta,22-triol, and (22R) cholest-5-ene-3 beta,22-diol-7-one was examined in suspension cultures of Ehrlich ascites tumor cells. The 7 alpha-hydroxy compound proved to be ineffective, whereas the latter two substances displayed a strong cytotoxic effect. PMID- 2875557 TI - A histochemical study of changes in mitochondrial enzyme activities of rat liver after ischemia in vitro. AB - Changes in the activity of three mitochondrial enzymes in rat liver after in vitro ischemia have been determined by enzyme histochemical methods. The changes were correlated with the appearance in the electron microscope of flocculent densities in the mitochondria indicative of irreversible cell injury. The flocculent densities were observed in rat liver after about 2 h of ischemia in vitro at 37 degrees C. At the same time the activity of glutamate dehydrogenase, localized in the mitochondrial matrix, started to decrease. However, the activities of succinate dehydrogenase localized in the inner membrane of mitochondria, as well as monoamine oxidase of the mitochondrial outer membrane did not change at that stage. It is concluded from the results of this study and those of others that flocculent densities are formed by denaturation of proteins of the mitochondrial matrix in which glutamate dehydrogenase takes part. It should be considered more as a sign than as the cause of cell death. PMID- 2875558 TI - Ultrastructural features of rectal epithelium of the mouse during the early phases of migration to repair a defect. AB - Observations were made by scanning and transmission electron microscopy on the migrating epithelial cells of the mouse rectum at intervals up to 24 h after stripping the epithelium off the mucosa. Resurfacing of the denuded basal lamina proceeded by the centrifugal migration of the columnar cells of the crypts. Changes in these cells occurred very rapidly. In less than 20 min a flat leading lamella developed and extended out on the basal lamina. The leading lamella could be recognized easily in scanning electron micrographs by the absence of microvilli, although these were retained on the cell body, gradually getting less regular and sparser than normal. Many zeiotic blebs appeared on the free margin of these cells. The features of migrating epithelium which are displayed in the in vivo repair of rectal mucosa are shared with migrating epithelia cultured in vitro. Goblet cells appeared not to be active in resurfacing the lesions. They disappeared from the surface epithelium, but were evident again by 18 and 24 h. The method of producing these lesions can also be used to study the cells that are removed. PMID- 2875559 TI - In vivo effects of toxic and detoxified endotoxin alone or in combination with muramyl dipeptide on lymphoid and non-lymphoid cells in the spleen of Meth A sarcoma-bearing mice. AB - In this study we confirmed that combinations of toxic or detoxified endotoxin with muramyl dipeptide (MDP) induced much more necrosis of transplanted Meth A sarcoma in mice than toxic endotoxin alone. Detoxified endotoxin and MDP alone had little antitumor effects. We investigated whether these divergent antitumor effects could be related to histopathological changes in the white pulp of the spleen of Meth A sarcoma-bearing mice. Toxic endotoxin reduced the T:B cell compartment ratio in the splenic white pulp by increasing the size of the B-cell compartment while leaving the size of the T-cell dependent inner PALS unaffected. The number of the T-lymphocytes in this area, however, was reduced. The border of B-lymphocytes in the marginal zone was markedly narrowed and the number of marginal metallophils along the inner border of the marginal sinus was decreased. None of these changes were observed after treatment with detoxified endotoxin or MDP. Addition of MDP to either endotoxin did not change their effects. The histopathological changes in the lymphoid and non-lymphoid compartments of the splenic white pulp are apparently exclusively induced by toxic endotoxin. As the antitumor activity of both toxic and detoxified endotoxin combined with MDP are about equal and more powerful than the activity of toxic endotoxin alone, it is concluded that these antitumor effects cannot be related to changes in the white pulp of the spleen. PMID- 2875560 TI - Mitigation of an anthracycline-induced cardiomyopathy by pretreatment with razoxane: a quantitative morphological assessment. AB - A quantitative evaluation of structural modifications was undertaken in the myocardium of daunorubicin (DNR)-treated and razoxane (RZ)-protected mice. BDF1 mice were injected with DNR, 15 mg/kg; a second group of mice was subjected to the same conditions but, in addition, received a pretreatment of RZ, 200 mg/kg. Representative cubes of myocardial tissue were processed for viewing with the electron microscope. Five hundred myocardial cells in each group were examined for the presence of lesions which had been categorized as early, moderate, or advanced. Contrasting the total number of demonstrable lesions in each group revealed a statistically significant reduction of 38% in abnormalities present in RZ-protected mice. By category, RZ-pretreated mice showed a mitigation in the appearance of early and moderate alterations and a striking reduction in the incidence of advanced, irreversible lesions. These results indicate that the cardiomyopathy associated with DNR administration can be ameliorated by pretreatment with RZ; this protective effect is markedly exerted by preventing the development of severe, irreversible lesions in the murine myocardium; the initial, non-transient structural alteration subsequent to DNR-exposure appears to affect the myocardial sarcoplasmic reticulum. PMID- 2875561 TI - [Gamma-glutamyl transpeptidase activity of the human brain]. PMID- 2875562 TI - [Electron microscopic study of the morphology of virus of hemorrhagic fever with renal syndrome in suckling mice]. PMID- 2875563 TI - [Success in establishing the MSHA-positive Pseudomonas aeruginosa fimbrial strain]. PMID- 2875564 TI - [Methodology and problems in the study of drugs of abuse in urine]. AB - The analysis of drugs of abuse in urine is a valuable tool for the detection of illicit drug use and the treatment and rehabilitation of addicts. In order for the results to be conclusive, however, several precautions have to be taken during the collection, storage, mailing and analysis of the urinary specimen. Since immunological methods for the determination of drugs of abuse are not completely specific, all positive results on immunoassay should be confirmed, at least for forensic purposes, by a chromatographic technique. Although much more complicated and time-consuming, some chromatographic techniques such as gas chromatography-mass spectrometry offer the possibility of unambiguously identifying drugs of abuse. However, in some cases, even with this method it is not possible to decide whether the identified metabolite of a drug of abuse stems from food or illicit or elicit drug use. A single urinary analysis is, therefore, sometimes not sufficient to provide unambiguous proof of the use of illicit drugs. However, definite evidence of repeated drug abuse can be obtained if the person involved is carefully instructed as to which medicines or food must not be taken during the investigation period and yet the analysis of several urinary specimens taken at intervals of one or two days proves positive. PMID- 2875565 TI - [Stimulation and inhibition of uterine contractions from the modern viewpoint]. AB - We know close to nothing why preterm or adterm delivery in human being starts. Either it is the breakdown of mechanisms protecting the pregnancy when it is time for the baby to flee the no more adequate surrounding of the uterus, or the activation of substances starting uterine contractions. Most probable is the interaction between oxytocin and prostaglandines which leads to the onset of labour; the influence of the fetus on this procedure is discussed. Stimulation of contractions: Oxytocin given as infusion with or without foregoing priming by locally applied prostaglandines (exact supervision of uterine motility and the well-being of the fetus by CTG) and/or amniotomy. Infusions of Prostaglandines always cause uterine contractions ending with the expulsion of the fetus. Inhibition of uterine contractility: In cases of threatening premature delivery before during and after intraabdominal operations and fetal distress during term delivery nowadays Betamimetics are given. The application of alcohol is reserved for special cases. PMID- 2875566 TI - Parathyroid surgery in the multiple endocrine neoplasia type I syndrome: choice of surgical procedure. PMID- 2875567 TI - Current approach to the management of tumoral process in patients with gastrinoma. PMID- 2875569 TI - [New knowledge in some areas of urinary tract infections in childhood]. PMID- 2875568 TI - [Diagnostic relevance of the De Ritis quotient and gamma-glutamyltransferase in alcoholic liver parenchyma damage]. PMID- 2875570 TI - Structure investigations of agonists of the natural neurotransmitter acetylcholine, IV. X-ray structure analyses of trimethylpentylammonium-chloride and (4-acetoxybutyl)trimethylammonium-iodide. AB - The crystal structures of the title compounds which display cholinergic activity at the ganglionic receptor have been determined by X-ray structure analysis. [(CH3)3N+C5H11]Cl- (1) crystallizes in the orthorhombic space group Pbnm with half a formula unit per asymmetric unit, a = 11.381(14), b = 12.871(17), c = 7.316(4) A. The intensities of 1106 independent reflections were collected with an automatic diffractometer. The structure refinement converged at R = 0.133 for the 355 observed reflections. The cation of 1 is disordered. [(CH3)3N+ (CH2)4-O C(O)-CH3]I- (2) crystallizes in the orthorhombic space group P2(1)2(1)2(1) with four formula units per unit cell, a = 16.783(8), b = 10.276(6), c = 7.427(10) A. The intensities of 1469 independent reflections were collected. The structure refinement converged at R = 0.071 for 1383 observed reflections. In both compounds the trimethylammonio methyl groups are coordinated nearly tetrahedrally by four anions in the first coordination sphere. Anions which occupy a special face type (B) of the tetrahedron of the (CH3)3N+ -CH2-group may be treated as a "model binding site" of the receptor. In the crystal structure of 2 the anions occupying B-type faces form together with the ammonium nitrogen and the carbonyl oxygen so called "Activity triangles". The almost equal geometries of these activity triangles are correlated with the mode of pharmacological action. PMID- 2875571 TI - Structure investigations of agonists of the natural neurotransmitter acetylcholine, V. Structure-activity correlations for cholinergic stimulants derived from crystal structures of their halides. AB - General features of crystal structures of halide salts of cholinergic stimulants can be interpreted in terms of substrate-receptor interactions. The monoatomic counterions in the crystal structures are discussed as models for the binding site of the receptor with respect to the ammonium group of the cholinergic neurotransmitters. In the crystal structures the anions occupy the tetrahedral faces of the quaternary trimethylammonio methyl or related groups in a specific geometry. Crystallographic and pharmacological evidence indicates that these groups should preferentially interact with the receptor via a specific face type (B-type face). The directionality of the interaction is derived from the vectors joining N+ with the anions occupying B-type faces. So called "activity triangles", formed by the nitrogen of the ammonium group, a second polar centre of the neurotransmitter cation and a counterion occupying a B-face of the ammonium group, provide a structural criterion for the differentiation between muscarinic and nicotinic activity. It is shown that structure-activity relationships of cholinergic stimulants do not depend on the conformational details of the neurotransmitter cations, but primarily on the relative positions of the polar centres of the cations with respect to the anionic binding site of the receptor. PMID- 2875572 TI - Structure investigations of agonists of the natural neurotransmitter acetylcholine. VI. X-ray structure analysis of trimethyl[2-(propionyloxy)ethyl] ammonium-iodide (O-propionylcholine-iodide). AB - The title compound crystallizes in the orthorhombic, noncentrosymmetric space group Pna2(1) with a = 10.241(11), b = 12.903(12), c = 9.312(9) A and with one formula unit per asymmetric unit. The stereochemically comparable torsion angles of the cation of 1 and of acetylcholine chloride are analogous. In the crystal structure the trimethylammonio methyl group is surrounded by three anions in the first coordination sphere. The geometry of a triangle formed by one of these counterions which occupies a special face of the N+C4 tetrahedron of the (CH3)3N+ CH2-R moiety, the nitrogen atom of the ammonium group and the oxygen atom of the carbonyl group is typical for nicotinic agonists. PMID- 2875573 TI - On schizophrenia: light at the end of the tunnel? PMID- 2875574 TI - [Quantitative relationship among immunoregulatory cells in patients with chronic pyoderma]. PMID- 2875575 TI - [Neuropharmacologic analysis of the process of generalization in the cat]. AB - Processes of generalization and abstraction were studied in intact cats before and after systemic administration of dopamine-, cholin- and GABA-ergic substances in conditions of free behaviour with food reinforcement by a developed method. It is shown that only inhibition or activation of dopaminergic system disturbs the function of generalization in animals. Some possible neurochemical mechanisms of generalization in animals are being analyzed. PMID- 2875576 TI - [Role of the brain noradrenergic system in transforming the stressor reactivity of brown rats selected for their domestication behavior]. PMID- 2875577 TI - [Central-acting analgesics]. PMID- 2875578 TI - [Water electrolysis--the basis of a hydrogen soldering device]. PMID- 2875579 TI - [Glutamine synthetase content and immunochemical analysis of different strains of Bordetella pertussis]. AB - In this investigation 3 groups of strains isolated from pertussis patients have been studied: typical (group 1), atypical in their cultural properties (group 2), unidentified Gram-negative bacilli agglutinated by pertussis and parapertussis antitoxins (group 3). Besides, B. pertussis cultures, obtained by subculturing 2 museum strains and 2 newly isolated strains on synthetic casein-charcoal agar with subinhibiting doses of antibiotics or specific immune sera added, have been studied. As indicated by the results of this study, strains belonging to groups 1 and 2 contain glutamine synthetase, while in strains of group 3 this enzyme is absent. In immunoelectrophoresis strains of group 3 have been found to contain not a single antigen similar to the antigens of strains belonging to groups 1 and 2. Electrophoresis in polyacrylamide gel has revealed to differences in the protein spectrum of the strains of these 3 groups. The investigation has shown that the determination of glutamine synthetase and immunoelectrophoresis can be used for the differentiation of B. pertussis from similar Gram-negative bacilli. B. pertussis strains, changed as the result of experiments with antibiotics and specific immune sera, have also been shown to retain their antigenic composition and protein spectrum and to have no essential difference in the content of glutamine synthetase. PMID- 2875580 TI - [Time periods of antibody preservation in patients convalescing from hemorrhagic fever with renal syndrome in European foci of the infection]. AB - The radioimmunoassay of serum samples from 76 convalescents after hemorrhagic fever with the renal syndrome (HFRS), that took place in 1964 in Ufa, revealed the presence of specific antibodies in 75% of the convalescents. The absence of antibodies may be attributed both to their loss in some of the convalescents and to mistakes in the clinical diagnosis. The study of serum samples from 19 convalescents who had the infection in 1960 during the laboratory outbreak of HFRS at the Gamaleya Institute of Epidemiology and Microbiology (Moscow) showed the presence of antibodies in all convalescents. In both groups the infection was linked with common red-backed voles (the Western serological variant of the virus). PMID- 2875581 TI - [Antipertussis immunity studied by immunoenzyme analysis]. AB - The levels of antibodies to disintegrated Bordetella pertussis and its individual fractions (protein and polysaccharide) in children immunized with different batches of adsorbed DPT vaccine have been determined with the use of EIA techniques. The background level of antibodies in the control groups has been determined, and in immunized children the levels of antibodies to disintegrated B. pertussis and its protein fraction have been shown to considerably exceed the levels of antibodies to lipopolysaccharide. PMID- 2875582 TI - [Various aspects of the treatment of epilepsy patients]. AB - On the basis of long-term clinical studies the author has analyzed the errors and drawbacks in the treatment of epileptic patients. This is the first paper appearing in the Soviet literature in which contraventions of the principles of the therapeutic process are considered in detail. Thus, it is shown that the use of only drugs or surgical treatment is not always sufficiently effective. The treatment should be comprehensive and variable with respect to both biological and social state of the patient. PMID- 2875583 TI - [Clinical picture, therapy and rehabilitation of patients with slowly-progressive (psychopath-like) schizophrenia with a loss of work capacity]. AB - A clinico-statistical study of therapy and rehabilitation of 37 patients with psychopath-like schizophrenia selected by the method of blanket sampling using a criterion of the loss of the working ability within 12 months and more showed high efficiency of comprehensive medicated and intensive socio-rehabilitative action (industrial therapy). The role of the stimulating component in the spectrum of psychotropic activities of neuroleptics in the treatment of psychopath-like schizophrenia was ascertained. The result of the work was the employment of 20 of the 37 patients studied. It was shown in 37 randomly selected disabled patients with slowly progressive (psychopath-like) schizophrenia that stimulating neuroleptics played a definite role in including methods of intensive socio-occupational therapy into the management of these patients. PMID- 2875584 TI - [Causes of ischemic stroke in young patients (review)]. PMID- 2875585 TI - N-methyl-N'-nitro-N-nitrosoguanidine and cyclic GMP stimulate phosphorylation of nuclear proteins from rat liver. PMID- 2875586 TI - Multiple endocrine neoplasia type I (MEN I). A wide range of clinical presentation. Report of three cases. PMID- 2875587 TI - Thyroid glands in patients with Graves' disease are sources of thyrotropin binding inhibitory (TBI) activity. AB - In order to investigate the main sources of production of Graves' immunoglobulins, 4 women with Graves' hyperthyroidism, which relapsed after withdrawal of methimazole (MMI) therapy, were selected for this study. The patients underwent subtotal thyroidectomy after pre-operative treatment with MMI and Lugol's solution. Seven blood samples were obtained in each patient during surgery from: a peripheral vein, immediately before neck incision; the carotid artery; and the left and right inferior thyroid veins, respectively, before manipulation of the thyroid; and the left and right inferior thyroid veins, respectively, after surgical handling of the gland; a peripheral vein at the end of operation. Thyrotropin-binding inhibitory (TBI) activity was measured in all samples by a radioligand method. Serum TSH was also measured in those samples. There was a substantial increment of TBI in the thyroid veins compared with the activity in the carotid artery. The mean TBI was significantly higher after surgical handling of the thyroid lobes. The two lobes from each gland secreted differing levels of TBI, whereas the TSH concentrations were similar in all samples from each individual patients. We conclude that at least part of the TBI activity in patients with Graves' disease comes from the lymphocytic infiltration of the glands, and that differences in antibody production between the thyroid lobes may explain the difference in TBI activity in their respective thyroid veins. PMID- 2875588 TI - Interactions between TSH binding inhibiting--and adenylate cyclase stimulating- antibodies in Graves' disease. AB - It is well known that there exists a dissociation between TSH binding inhibiting antibody (TBIAb) and thyroid stimulating antibody (TSAb) in some patients with Graves' disease. The present studies were undertaken to investigate the interaction between TBIAb and TSAb quantitatively using porcine thyroid cells in order to determine whether the binding sites of TBIAb and TSAb are identical or independent from each other. TBIAb was determined using solubilized porcine thyroid membrane and TSAb using cultured porcine thyroid cells, and both were expressed as equivalent amounts of bovine TSH. In order to avoid interassay variations, all determinations were performed with a single batch of porcine thyroids. Serum samples were obtained from ten untreated patients with Graves' disease; two were negative for TBIAb and TSAb, two were TBIAb negative and TSAb positive, two were weak positive for both, two were strong positive for both, and two were TBIAb strong and TSAb weak positive. IgG from each patient were mixed with equal amounts of IgG of the other nine patients. In order to observe interactions, measured values for TBIAb and TSAb of mixed samples were compared to estimated values (addition of values of original samples). The correlation coefficient between measured values and estimated values for TBIAb was +0.964, and that for TSAb was +0.989. These results that TBIAb does not interfere with the activity of TSAb and vice versa suggest that at least in some patients with Graves' disease, TBIAb and TSAb are different antibodies which have different binding sites. PMID- 2875589 TI - Assay for thyroid growth stimulating immunoglobulins: stimulation of [3H]thymidine incorporation into isolated thyroid follicles by TSH, EGF, and immunoglobulins from goitrous patients in an iodine-deficient region. AB - Estimations were carried out of [3H]thymidine incorporation during culture of isolated porcine thyroid follicles in the presence of standard TSH or epidermal growth factor (EGF) both alone and together with anti-TSH or anti-EGF serum, and of immunoglobulins fractionated from the sera of patients from our endemic goitre area with iodine deficiency. A significant stimulation of thymidine incorporation was exerted by TSH when thyroglobulin was present in the culture medium, and also by EGF. TSH stimulation was abolished by anti-TSH serum, in contrast to the effect of EGF. Anti-EGF serum, on the other hand, blocked the effect of EGF, but not that of TSH. The sera of 20 out of 72 patients (27%) with euthyroid goitre (not operated on) and of ten out of 26 patients (38%) with recurrent euthyroid goitre contained immunoglobulins stimulating thyroid growth (TGI). There was no correlation of TGI with other thyroid antibodies. TGI have to be regarded as a pathogenetic factor of euthyroid goitre also in patients from an endemic region especially in recurrent cases. PMID- 2875590 TI - Non-pituitary actions of somatostatin. A review on the therapeutic role of SMS 201-995 (sandostatin). AB - Natural Somatostatin has a short half-life (3 min), is only active after intravenous administration and causes a rebound hypersecretion of hormones after discontinuation of administration. Recently a long-acting powerful Somatostatin analog was developed (SMS 201-995; Sandostatin) which has a half-life of 113 min after subcutaneous administration. After administration of this analog no rebound hypersecretion of hormones was observed. In the present review the effects of the acute administration and of long-term treatment with SMS 201-995 in acromegalic patients is discussed. In addition the potential role of therapy with Somatostatin analogs and the preliminary effects of Somatostatin and/or SMS 201 995 are discussed in disorders of gastro-intestinal function (haemorrhages, diarrhoea, pancreatitis and endocrine pancreatic tumours), diabetes mellitus, central nervous system disturbances and oncology. Finally, several aspects of the tolerance, tachyphylaxis and side effects of SMS 201-995 are discussed. PMID- 2875591 TI - Non-pituitary actions of hypothalamic hormones. Functional significance and therapeutic implications. General introduction. PMID- 2875592 TI - Non-pituitary actions of hypothalamic hormones. A look in the future. PMID- 2875593 TI - Efficacy of lorazepam and lormetazepam as intravenous premedicants for anesthesia and surgery. AB - Lorazepam 4 mg and lormetazepam 2 mg were compared as intravenous premedicants by assessing their effects on the level of consciousness and anxiety, sensory and motor functions, neuromuscular function and vital parameters in sixty surgical patients in a randomized study. Lormetazepam exerted a marked sedative-hypnotic effect maximal at 10 min. Lorazepam had a slower onset of action with a peak effect at 40 min on the different neurobehavioral functions but seemed to induce a longer duration of sedation and a more consistently obtunded awareness of perisurgical events than lormetazepam. Sensory functions were similarly affected by both drugs. Motor function was significantly more impaired by lormetazepam than by lorazepam (P 0.05). Both drugs significantly decreased anxiety for at least 60 min after premedication. Important changes of muscle tone were noticed with lormetazepam at 10 to 30 min resulting in upper airway obstruction in some patients. All hemodynamic changes remained clinically acceptable in both groups and no side effects were seen. The clinical anesthesiologists rated the quality of premedication as unsatisfactory in 7% of the patients treated with lorazepam and in 27% of those receiving lormetazepam. Together with its milder neurobehavioral effects and highly effective anxiolytic action, these factors favor the use of lorazepam for anesthetic premedication despite a relatively slow onset of action. PMID- 2875594 TI - Midazolam for intramuscular premedication: dose-effect relationships compared to diazepam, fentanyl and fentanyl-droperidol in a placebo controlled study. AB - The clinical effects of midazolam (7.5, 10 and 15 mg), diazepam 10 mg, fentanyl 0.1 mg and fentanyl 0.1 mg-droperidol 5 mg, administered intramuscularly for surgical premedication, were compared in a double-blind placebo-controlled study. The degree of sedation provided by midazolam was significantly superior to diazepam, fentanyl or placebo. The largest dose of midazolam also impaired the lucidity of the patients and induced a moderate degree of muscular hypotony. A dose-effect relationship was observed only for the sedative effects of midazolam 60 min after administration. Midazolam scored consistently better than diazepam, fentanyl, placebo and fentanyl-droperidol for incidence of amnesia, stability of cardiovascular measurements and physician's acceptance. In all treatment groups, including placebo, anxiety decreased significantly with time. However, if expressed as percentage change, the greatest decrease occurred in the midazolam 15 mg group compared to all other treatments. Midazolam appeared to be a more effective premedicant than diazepam, analgesics or placebo. The intensity of the combined central nervous system effects suggested the dose of 10 mg might be the most suitable for intramuscular premedication. PMID- 2875595 TI - The neuromuscular blocking action of vecuronium in normal patients and in patients with no renal function and interaction vecuronium-tobramycin in renal transplant patients. AB - The new short acting steroid muscle relaxant vecuronium was tested clinically in 42 surgical patients and compared in three different groups of patients: normal patients, renal graft patients who received tobramycin preoperatively and other anephric patients undergoing surgery. Twenty-five percent recovery of initial twitch height as measured by NTM was significantly longer in the renal graft group than in the two other groups where recovery time is normal. Cardiovascular parameters were recorded before and after the injection of vecuronium. Reversal of the neuromuscular block was spontaneous or pharmacologically evoked by neostigmine. Clinical recovery was complete in all patients and there was no residual block. PMID- 2875596 TI - Proliferative myositis and fasciitis. Report of five cases with an ultrastructural and immunohistochemical study. AB - Cases of proliferative myositis and fasciitis were studied immunohistochemically and ultrastructurally for further understanding of the nature of ganglion cell like giant cells. Blood coagulation factor XIIIa, fibronectin, myoglobin, myosin, CPK MM, and alpha-1-antichymotrypsin were detected in three cases of proliferative myositis and two cases of proliferative fasciitis by the avidin biotin-peroxidase complex method. Factor XIIIa (a fibrin-stabilizing factor) and fibronectin were strongly positive in the giant cells, but not in striated muscle fibers. A small quantity of myosin was demonstrated in the giant cells, but myoglobin and CPK MM were never demonstrated in these cells. No alpha-1 antichymotrypsin was demonstrated in the giant cells. One case of proliferative myositis showed ultrastructural features suggestive of fibroblast rather than muscle cell or histiocytic origin. Strongly positive factor XIIIa in the giant cells is suggestive of the fact that they are active fibroblasts. PMID- 2875598 TI - [Studies on the quaternary alkaloids of Rauwolfia verticillata (Lour.) Baill var. hainanensis Tsiang]. PMID- 2875597 TI - Perineurial cell tumor and the significance of the perineurial cells in neurofibroma. AB - The authors attempted to clarify the exact cell components of neurofibroma by immunohistochemical and ultrastructural studies. Materials were randomly selected, 40 cases of neurilemoma and neurofibroma (-tosis) in addition to 2 cases of tumors composed exclusively of perineurial cells and three cases of normal peripheral nerve. The applied markers included antisera of S-100 protein for Schwann cells, blood coagulation factor XIIIa for endoneurial fibroblasts or perineurial cells, and laminin and collagen type IV for the basement membrane. S 100 protein was demonstrated only in normal or neoplastic Schwann cells, but not in perineurial cells. On the other hand, factor XIIIa was often recognized in endoneurial fibroblasts and perineurial cells, but not in Schwann cells. Neurofibroma was basically composed of a mixture of Schwann cells, perineurial cells, and endoneurial fibroblasts, the population of each type of cell differing according to the case and area within a given tumor. Perineurial cell tumor exclusively composed of perineurial cells, though rare, appears to be a definite entity, and its characteristic histological and ultrastructural features were described. PMID- 2875599 TI - Anticonflict properties of the dipeptide Litoralon and of diazepam in rats. AB - The anticonflict properties of the anxiolytic diazepam and of the dipeptide Litoralon gamma-L-glutamyl-taurine and two of its analogues SZJ 3388, gamma aminobutyryl-ethanolamine phosphate, and SZJ 3361, D-1 aminoisobutyrylethanolamine phosphate have been investigated in a "time-to emerge" conflict paradigm in non-deprived rats. Diazepam, Litoralon and compound SZJ 3388 significantly decreased the "time-to-emerge" latency (TTE latency) in a dose-dependent manner versus saline- or vehicle-treated controls in doses between 0.05 and 0.50 mg/kg intraperitoneally. The analogue SZJ 3361 was inactive as regards the TTE latency, while the anti-histaminic promethazine lengthened the TTE latency in a dose-dependent manner. The number of irresolute responses was significantly decreased following administration of diazepam, SZJ 3388 and Litoralon and was positively correlated with the TEE latency-decreasing activity of these compounds. The data are discussed in terms of the benzodiazepine-like anxiolytic or anti-conflict properties of these dipeptides. PMID- 2875601 TI - Angiotensin II infusion during beta-adrenergic stimulation by isoproterenol. Effects on hepatic, splenic and cardiac blood volumes and on the magnitude and distribution of cardiac output in the dog. AB - The cardiac and peripheral vascular adjustments to angiotensin II (0.1-0.2 microgram kg-1 min-1 i.v.) during high beta-adrenergic activity by a continuous isoproterenol infusion (0.2-0.3 microgram kg-1 min-1 i.v.) were examined in anaesthetized, atropinized dogs. Hepatic, splenic and left ventricular (LV) volume changes were estimated by an ultrasonic technique, and the blood flow distribution was measured by injecting radioactive microspheres and by electromagnetic flowmetry on the caval veins, the hepatic artery and the portal vein. During isoproterenol infusion, angiotensin II increased the systolic LV pressure by 45 +/- 3 mmHg and the stroke volume by 17 +/- 6%. Concomitantly, the hepatic and splenic blood volumes declined by 29 +/- 4 and 14 +/- 6 ml, respectively, and the LV end-diastolic segment length increased by 3 +/- 1%. The flow through the inferior caval vein increased by 39 +/- 9%, whereas the superior vena caval flow remained unchanged. The hepatic arterial flow more than doubled. Thus, at high inotropy by isoproterenol infusion, angiotensin II relocates blood from the liver and the spleen towards the heart. By activating the Frank-Starling mechanism, cardiac output is increased and conducted through the lower body, especially through the hepatic artery, because of the poor autoregulation of flow through this vessel. PMID- 2875600 TI - Effects of N-ethylmaleimide and forskolin on glutamate release from rat hippocampal slices. Evidence that prejunctional adenosine receptors are linked to N-proteins, but not to adenylate cyclase. AB - In the present experiments we have examined the effect of N-ethylmaleimide (NEM) on the release of [3H]glutamate from rat hippocampal slices. Pretreatment of slices with NEM in a concentration between 50 microM and 200 microM, can inhibit the GTP-binding protein (Ni) that transmits receptor signals into inhibitions of adenylate cyclase, without affecting the Ns-protein, that transmits signals into stimulation of the cyclase, or the cyclase. The adenosine receptor agonist R phenylisopropyladenosine (R-PIA, 1 microM) caused an approximately 50% inhibition of the evoked [3H]glutamate release. This effect was completely prevented by NEM treatment, which did not affect basal or stimulated release of the amino acid. By contrast, the effect of R-PIA was unaffected by adding an adenylate cyclase stimulator (forskolin 1 microM) and a phosphodiesterase inhibitor (rolipram, ZK 62.711, 30 microM) which raised the cyclic AMP content of the slices approximately 10-fold. In conclusion, these results suggest that the adenosine receptor that mediates prejunctional inhibition of glutamate release is coupled to a protein similar to the Ni-protein, but that another effector than adenylate cyclase is involved. PMID- 2875602 TI - Sympathetic nerve activation decreases the release of vasoactive intestinal polypeptide from the feline intestine. AB - The splanchnic nerves to the small intestine were stimulated in anaesthetized cats. Activation of the sympathetic nerves caused vasoconstriction, increased net fluid absorption and decreased release of vasoactive intestinal polypeptide (VIP) in the small intestine. In the colon, parasympathetic nerve stimulation elicited vasodilatation and increased release of VIP. Additional stimulation of the sympathetic lumbar colonic nerves decreased the colonic blood flow and inhibited the release of VIP. These effects of the stimulation of the lumbar colonic nerves were blocked by phentolamine. It is concluded that, in the feline intestine, sympathetic nerve stimulation presynaptically decreased the release of VIP via an alpha-adrenergic mechanism. PMID- 2875603 TI - Effect of alpha, beta-methylene ATP on distal colonic and rectal motility--a possible involvement of P2-purinoceptors in pelvic nerve mediated non-adrenergic, non-cholinergic contraction. AB - The possible involvement of purinoceptors in the parasympathetic nervous control of large intestinal motility was investigated in cats anaesthetized with chloralose and treated with adrenolytics. Distal colonic and rectal motor responses to efferent pelvic nerve stimulation (PNS) and drugs injected close i.a., were recorded by a volumetric method. Single dose i.a. injections of alpha, beta-methylene ATP (mATP) induced colonic and rectal contractions which were resistant to atropine, hexamethonium and indomethacin, as well as to the nerve blocking agent tetrodotoxin. Repeated injections of mATP were followed by attenuated motor responses and eventually complete tachyphylaxis to the compound developed. In the presence of atropine, or a combination of hexamethonium and atropine, contractions elicited by PNS were inhibited during mATP tachyphylaxis. In contrast, prior to such anticholinergic drugs, or in the presence of hexamethonium alone, pelvic nerve mediated contractions persisted despite mATP tachyphylaxis, which did not affect the colonic and rectal contractions evoked by acetylcholine or histamine. The results suggest that P2-purinoceptors are involved in non-adrenergic, non-cholinergic large intestinal excitatory motor responses to PNS. PMID- 2875604 TI - Regional distribution and extracellular levels of amino acids in rat central nervous system. AB - The extracellular levels of aspartate, glutamate, serine, glutamine, glycine, alanine and GABA were studied in vivo with the microdialysis technique in 15 different regions of the rat brain. The effect of high K+ on the overflow of these amino acids was also studied. These results were compared with those from a regional dissection of 17 brain regions in which the tissue content of the same amino acids was determined. The in vivo data showed an unevenly distributed KCl response of aspartate, glutamate, taurine and GABA, all of which are putative neurotransmitters. It was not possible to predict the response to high K+ from the magnitude of the unstimulated overflow. Glutamine overflow was inversely related to that of glutamate during the high K+ stimulus, which is consistent with glutamine being the main precursor of glutamate. Only for GABA and alanine was overflow proportional to the tissue level in the different regions studied. PMID- 2875605 TI - [Overall results of attempts to treat schizophrenia by hemodialysis. Reflections on the placebo effect in a psychosis]. AB - A review is made of 325 published cases of schizophrenic patients who underwent series of hemodialysis. In 211 cases the series of dialysis were open studies; 49 of these patients (23%) were markedly improved. In 114 other patients the effects of actual and sham dialysis were compared in a double blind experiment. A marked improvement was found in 24 cases (21%). But results of sham and actual hemodialysis did not differ significantly. Hemopurification is therefore not the cause of improvement. The rate of marked improvement is however clearly higher than what one could expect in chronic schizophrenics from a simple placebo effect. The various possible causes for this special effect are discussed. It is proposed that about 20% of schizophrenic patients could favorably react to the strong healing involvement of the psychiatrist, especially when a magic aspect is implied. This should encourage to approach patients not responding to conventional therapy with more optimism and possibly with new methods. PMID- 2875606 TI - [Valpromide (Depamide) in the treatment of acute psychotic states. Open clinical study]. AB - In an open clinical study on the effect of Depamide in acute psychosis, 59 schizophrenic and 23 manic hospitalized patients were tested. They were divided in two groups: in group A, Depamide was administered only after an initial period of treatment with haloperidol or chlorpromazine; in group B instead, Depamide was added from the beginning of the neuroleptic treatment. The results show that the association of Depamide with neuroleptics leads to a reduction of agitation and of the hospitalization period, whereas it ameliorates the adaptation of the patients to the therapeutic milieu. PMID- 2875608 TI - Characterizing paranoia in the DSM-III borderline personality disorder. AB - The relationship between paranoia and the borderline personality disorder continues to be the subject of debate. This study compares the extent and intensity of paranoia in 29 subjects fulfilling DSM-III criteria for borderline personality disorder. The control group consists of 22 subjects with dysthymic disorder. Paranoia was both more prevalent and severe in borderline patients. Results are discussed in light of previous descriptive and research literature. PMID- 2875607 TI - History and current status of sedative-hypnotic drug use and abuse. AB - Sedative-hypnotic drug use and abuse increased in Europe after World War II and peaked about 1972. Clinical and follow-up descriptions of abusers support the concept of a psychiatric addiction syndrome, different from a low-dose withdrawal syndrome. Although these drugs may be prescribed unnecessarily, large portions of the general population with pathological psychic distress and insomnia do not receive psychotropic treatment, in spite of findings pointing to genetic and biochemical factors in the genesis of these. Research on underlying mechanisms and the rationale for maintenance therapy is needed. PMID- 2875609 TI - Respiratory irregularity and tardive dyskinesia. A prevalence study. AB - In a survey of 351 chronically hospitalized adult psychiatric patients, clinical evidence of irregular respiration compatible with respiratory tardive dyskinesia was present in eight subjects (2.3%). In four, audible involuntary respiratory noises were present. All patients with respiratory irregularities had a facio bucco-lingual dyskinesia and in four the dyskinesia also involved extremities and/or other regions of the body. The prevalence of respiratory irregularities amongst patients with tardive dyskinesia was eight out of 108 (7.4%); none of the patients without tardive dyskinesia had respiratory irregularities. The prevalence of respiratory irregularities was significantly greater in patients with an organic mental disorder (11.1%) compared with those without (1.3%) (P less than 0.005). None of the patients complained of their respiratory symptoms and none had been diagnosed as having a respiratory dyskinesia prior to the survey. In two patients the symptoms were severe, leading in one case to prominent gasping, dysphagia, severe choking when eating, and episodes of aspiration pneumonia. In a second patient the noisy respiration was interpreted as attention-seeking and intimidating behaviour which led to rejection by the staff. In the remaining six patients respiratory symptoms were relatively minor. PMID- 2875610 TI - Current outcome in schizophrenia: women vs men. AB - This article reviews the 1980's literature on gender differences in schizophrenia outcome. Neuroleptic response, long-term course, and housing, appear to be superior in women. Mortality ratios are advantageous to schizophrenic men. After menopause, women may require higher neuroleptic doses than men and are more at risk for severe tardive dyskinesia. The antidopaminergic effects of estrogens appear to be responsible for some of the outcome differences. PMID- 2875611 TI - Prevalence of tardive dystonia. AB - Tardive dystonia is a rare late-onset side effect of neuroleptics. This paper presents a prevalence study of 351 inpatients conducted in our hospital. Seven patients (2%) were found to suffer from this condition. The majority were found to be young and had received neuroleptics for a variable number of years before the onset of the dystonia. In general, treatment of this condition is disappointing. PMID- 2875612 TI - Neuropharmacology and the human brain. PMID- 2875614 TI - Alcohol withdrawal: clinical symptoms and management of the syndrome. PMID- 2875613 TI - Clonidine in abstinence reactions: basic mechanisms. PMID- 2875615 TI - Chlormethiazole--mode of action. AB - Studies in mice demonstrated that the anticonvulsant profile of chlormethiazole differs from that of diazepam and the barbiturates. Chlormethiazole protects animals from convulsions induced by a wide variety of chemoconvulsants known to block the action of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), such as bicuculline, picrotoxin, isoniazid and pentetrazol, thus confirming and extending earlier studies on its broad anticonvulsant characteristics. Chlormethiazole is particularly potent against isoniazid-induced convulsions, which are probably induced by reductions of GABA levels in the brain. Chlormethiazole was found to have a weak action on benzodiazepine receptor binding, GABA receptor binding and kainic acid receptor binding. Chlormethiazole inhibited picrotoxin binding at very high concentrations, but lowered the functional effects of picrotoxin at much lower concentrations than those affecting picrotoxin binding. Moreover, chlormethiazole failed to change GABA or glutamate levels in the brain and did not affect glutamic acid decarboxylase (GAD) activities in the rat brain. Muscimol (a GABAA agonist) enhanced the anticonvulsant activity of chlormethiazole against picrotoxin but not against bicuculline-induced convulsions. Muscimol enhanced the anticonvulsant potency of diazepam against both chemoconvulsants. These data suggest that the anticonvulsant activity of chlormethiazole is not mediated directly through changes in GABA or glutamate levels or by a direct (agonist) action at the GABA or benzodiazepine receptor complex. These findings suggest that chlormethiazole may enhance GABA transmission beyond the GABA receptors, hypothetically at the level of the GABA receptor coupled ionophore (e.g. the chloride ion channel). Applied micro-iontophoretically, chlormethiazole was found to potentiate the inhibitory responses to GABA, muscimol and glycine, but not to acetylcholine. The potentiation of glycine-mediated inhibition is unique for chlormethiazole and does not occur with any other known anticonvulsant (barbiturates, benzodiazepine, phenytoin or sodium valproate). Studies in primary cultures, derived from spinal cord neurones, showed that chlormethiazole produces hyperpolarization together with an increase in the threshold for action potential generation. Further in vitro studies indicated that chlormethiazole acts on some types of Ca2+-dependent chloride ion channels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2875616 TI - Comparative investigation of chlormethiazole and neuroleptic agents in the treatment of alcoholic delirium. AB - A retrospective study comparing the efficacy of chlormethiazole and neuroleptic agents showed that a mortality rate of 0% was associated with chlormethiazole treatment and 6% with neuroleptic treatment (P less than 0.005). Data from the literature support this result. Chlormethiazole treatment seems to be superior to the neuroleptic treatment of alcoholic delirium. PMID- 2875617 TI - The influence of chlormethiazole in comparison to thioridazine on body temperature and postural hypotension in healthy adults and healthy elderly volunteers. AB - Certain drugs used to treat the elderly are known to precipitate hypothermia. In this study, the effects of chlormethiazole and thioridazine in producing postural hypotension were compared. In a study of hypothermia in the elderly the effects of chlormethiazole, thioridazine and lormetazepam were examined. Only three patients showed a postural drop following chlormethiazole, while 11 showed a postural drop following thioridazine. Chlormethiazole showed little variation from the control group in the hypothermia study, while thioridazine and lormetazepam caused a fall in temperature. For behaviour control in the elderly and for a short course as a hypnotic, chlormethiazole seems to be safer than thioridazine or lormetazepam. PMID- 2875618 TI - The influence of chlormethiazole on the neuro-endocrine system in chronic alcoholics. AB - The neuro-endocrine system is affected by chronic ethanol ingestion. Chlormethiazole is effective in the treatment of the ethanol withdrawal syndrome because of its tolerability, lack of hepatotoxicity, short plasma half-life, lack of any long-acting intermediate metabolites and lack of adverse effects on the neuro-endocrine system in alcoholics. PMID- 2875619 TI - Sleep disturbances and agitational states in the elderly. Therapeutic possibilities and limitations in West Germany. AB - Sleep disturbance is common in the elderly. The causes of sleep disturbance are varied, and no single treatment can be successful in all cases. Psychotropic drugs and hypnotics are the drugs most frequently prescribed to the elderly in West Germany. The indications for using benzodiazepines, chlormethiazole, butyrophenones and chloral hydrate are discussed. However, in all cases the underlying cause of the sleep disturbance should be sought rather than treating the symptoms in isolation. PMID- 2875620 TI - Special problems relating to the use of hypnotics in the elderly. AB - The problems experienced by elderly patients taking hypnotic drugs are reviewed. They include those associated with accumulation, tolerance, drug dependence and the intensity and duration of response. Biological mechanisms associated with ageing enhance some of these effects in the elderly. Care should be taken to define the precise indications for hypnotic use and to choose the correct drug and dose for the patient's condition and age. PMID- 2875621 TI - A double-blind comparison of chlormethiazole and temazepam in elderly patients with sleep disturbances. AB - The results of this double-blind study showed that both chlormethiazole and temazepam are effective, in the correct dose, for the short-term treatment of sleep disturbance in elderly patients. With chlormethiazole treatment there was no daytime drowsiness, whereas significant daytime drowsiness occurred with temazepam. PMID- 2875622 TI - [Presence of atypical germ cells in cryptorchid testicles]. PMID- 2875623 TI - [Polyorchidism: review and contribution of a new case]. PMID- 2875624 TI - [Alminoprofene for inflammatory lesions and surgical pain in oral medicine]. PMID- 2875625 TI - Application of recDNA techniques to the production of ATP and glutathione by the "Syntechno System". PMID- 2875626 TI - Mitochondrial transmembrane proton electrochemical potential, di- and tricarboxylate distribution and the poise of the malate-aspartate cycle in the intact myocardium. PMID- 2875627 TI - Calcium channel blockers, beta blockers and the maintenance of calcium homeostasis. PMID- 2875628 TI - Alcohol and substance abuse: current issues of concern. PMID- 2875629 TI - The pathophysiology of bronchial asthma and targets for its drug treatment. PMID- 2875630 TI - The characterization of lodoxamide, a very active inhibitor of mediator release, in animal and human models of asthma. AB - A most active biologue of disodium cromoglycate (DSCG) available, lodoxamide tromethamine (LT), has been studied and characterized pharmacologically, in animal and human models of asthma. It has self-tachyphylaxis, but has oral activity (lodoxamide ethyl) in rats, primates, and man. In rats (LT) was 2,500 X more active than DSCG (ID50 = 0.001 mg/kg), in primates the drug was also active by several routes (inhalation 1 microgram/kg, IV 0.001 mg/kg, and oral 10 mg/kg). In isolated rat peritoneal mast cells, the compound displayed a biphasic dose response inhibition to histamine release initiated by (48/80, anti-IgE, and the calcium ionophore A23,187) with IC50 values of 0.1-50 microM. The consistent finding relating to its mode of action was its ability to inhibit 45calcium flux into the mast cell in response to antigen or A23,187. Clinical evaluations of lodoxamide tromethamine showed that at aerosol doses of 1.0 mg or less, it demonstrated significant inhibitory activity against antigen or exercise induced bronchospasm. However, in pilot evaluation studies in clinical asthma settings, the compound could not be shown to spare bronchodilator usage, relative to placebo, or be shown to be more effective than placebo treated patients based on other clinical endpoints. The reason for rat and primate models not being predictive for human long-term clinical asthma in the characterization of anti release compounds is not known. PMID- 2875631 TI - Inhibition of Paf-acether-induced edema of the rat's paw. AB - Three classes of drugs were found, after their i.p. administration, to inhibit Paf-acether-induced edema of the rat's paw. These were beta-adrenergic agonists (isoproterenol, salbutamol), alpha-adrenergic antagonists (prazosin, ergotamine, yohimbine, phenoxybenzamine), and calcium entry blockers (nifedipine, verapamil, diltiazem). A number of other drugs including steroidal and nonsteroidal antiinflammatory agents, alpha-agonists, beta-antagonists, pyrilamine, atropine, methysergide, a lipoxygenase inhibitor, and a leukotriene antagonist did not inhibit the development of the edema. Propranolol, but not practolol, antagonized the inhibitory effect of isoproterenol which provided evidence for involvement of beta-2 receptors in the mechanism of action of the beta agonists. It is suggested that cellular calcium influx is involved in the edemagenic response observed after the injection of Paf-acether into the rat's paw. PMID- 2875632 TI - Enhanced formation of sulfidopeptide-leukotrienes in ulcerative colitis and Crohn's disease: inhibition by sulfasalazine and 5-aminosalicylic acid. AB - Release of sulfidopeptide (SP)-leukotrienes (LT) in vitro from normal human colonic mucosa and from mucosal tissue obtained from patients with Crohn's disease (CD) and ulcerative colitis (UC) was investigated. It was found that inflamed mucosal tissue released significantly more SP-LT than normal colonic mucosa both under control conditions and after addition of calcium ionophore A23187. These results indicate the presence of endogenous stimuli as well as an increased responsiveness to an exogenous stimulus of LT formation in the inflamed mucosa. Sulfasalazine (SASP), a drug used in inflammatory bowel diseases, and its active metabolite 5-aminosalicylic acid (5-ASA) were found to inhibit colonic mucosal SP-LT formation, while only 5-ASA inhibited simultaneously synthesis of another arachidonic acid-derived inflammatory mediator, prostaglandin (PG) E2. The results suggest that SP-LT might be important mediators of inflammation in CD and UC. PMID- 2875634 TI - [The influence of intravitreal injection of a beta-blocker on the c-wave of the rabbit ERG]. PMID- 2875635 TI - [Periarteritis nodosa of the epididymis]. AB - A thirty-one-year-old man with a scrotal swelling on the left side was found to have periarteritis nodosa of the epididymis (epididymal arteries). No systemic symptoms were present. Review of the literature revealed only two similar cases. PMID- 2875633 TI - Pharmacological studies of antigen-induced arthritis in BALB/c mice. II. The effects of second-line antirheumatic drugs and cytotoxic agents on the histopathological changes. AB - The effects of treatment with second-line antirheumatic drugs and cytotoxic agents on the severity of experimental monoarticular arthritis in BALB/c mice have been investigated. The arthritis was assessed histologically in terms of synovitis and erosions of cartilage and bone. Azathioprine (20 mg/kg) and sulphasalazine (10-30 mg/kg oral; 30-100 mg/kg i.p.) produced significant suppression of synovitis and erosions when administered daily for 4 weeks commencing 2 weeks after induction of the arthritis. Dapsone (1-10 mg/kg) and to a lesser extent methotrexate (2 mg/kg) produced some suppression of erosive disease when administered daily for 4 weeks commencing 2 weeks after induction of the arthritis but this failed to reach statistical significance. Chloroquine, D penicillamine and sodium aurothiomalate all failed to have any effect on the disease with any of the treatment schedules used. Auranofin had no effect on the disease when treatment commenced 2 weeks after intra-articular injection but produced variable suppression at high doses when administered from the day of intra-articular injection. PMID- 2875636 TI - Serum enzyme determination in the study of liver disease in dogs. PMID- 2875637 TI - Fieldside management of athletic injuries. AB - A physician trained in the management of sports-related injuries should be in attendance at athletic events with a potential for significant injury. These are usually contact sports, particularly football. While many of the expected injuries are orthopedic in nature, the risk of serious injury to the larynx, abdomen, eyes and teeth also exists. PMID- 2875638 TI - Tailoring the antihypertensive drug regimen. AB - The challenge to the clinician is the need to choose among an array of antihypertensive agents in order to arrive at a regimen that is not only effective but also safe and convenient. Tailoring the regimen to the individual patient requires careful consideration of the pathophysiologic mechanisms that may be operative, concurrent risk factors and diseases, previous responses to other antihypertensive agents and the patient's general lifestyle, including diet and exercise. PMID- 2875639 TI - Post-traumatic stress disorder. PMID- 2875640 TI - Office management of anaphylaxis. AB - The primary therapy for anaphylaxis is epinephrine, which should be stocked in the office in the appropriate dilution (1:1,000). Antihistamines and corticosteroids are useful adjunctive agents that may be given in the office. Patients with progressive or severe symptoms should be transferred immediately to a facility where monitoring is available and vasopressors can be administered. Various measures can be taken to prevent anaphylaxis or limit its severity. PMID- 2875641 TI - Intravenous esmolol for the treatment of supraventricular tachyarrhythmia: results of a multicenter, baseline-controlled safety and efficacy study in 160 patients. The Esmolol Research Group. AB - Efficacy and safety of esmolol in the treatment of supraventricular tachyarrhythmias (SVT) was evaluated in this open-label, baseline-controlled, multicenter study. One hundred sixty patients with SVT received an intravenous infusion of esmolol in doses ranging from 25 to 300 micrograms/kg/min for up to 24 hours. All of the 160 patients were evaluated for safety, and 147 of them were eligible for evaluation of therapeutic response. Therapeutic response was defined as greater than or equal to 15% reduction in the average baseline heart rate of conversion to normal sinus rhythm. Seventy-nine percent (116 of 147) of the patients exhibited a therapeutic response. The cumulative percentage response increased significantly with increasing esmolol doses up to 200 micrograms/kg/min. The mean (+/- SEM) dose of esmolol producing a therapeutic response was 97.2 +/- 5.5 micrograms/kg/min. Among all patients (n = 160), 39% exhibited hypotension. In 58% of these patients, hypotension resolved with or without adjustment of the esmolol dose while the infusion continued; among almost all of the remaining patients, hypotension resolved within 30 minutes after esmolol was discontinued. Most patients at risk for adverse effects during beta blockade (i.e., those with diabetes mellitus, congestive heart failure, asthma, etc.) tolerated esmolol therapy, and there were no clinically important trends among the reported changes in laboratory variables. The results of the study indicate that esmolol is effective and well tolerated for the treatment of SVT. PMID- 2875642 TI - Clinical and research applications of ambulatory Holter ST-segment and heart rate monitoring. AB - Monitoring of the electrocardiogram during normal daily activity yields data regarding silent myocardial ischemia and its relation to heart rate in addition to the detection of cardiac arrhythmias. In recent years various techniques have been developed to quantify the frequency and duration of ischemic episodes in patients with ischemic heart disease. Of particular importance are the newer frequency-modulated recording techniques, which ensure adequate low frequency response, and the computerized digital analysis used to define the role of ST segment monitoring in the clinical and research setting. The techniques used for acquiring artifact-free signals, the methods of data analysis and the clinical role of ambulatory Holter monitoring of ST-segment changes in the diagnosis of Prinzmetal's angina, in chronic stable angina and in the detection of calcium antagonist withdrawal syndrome in angina are discussed. The data indicate the particular utility of Holter monitoring to analyze the variability of heart rate in defining the effects of calcium-channel blockers, beta-adrenergic blocking agents and their combined use in pharmacologic therapy of ischemic myocardial syndromes. PMID- 2875644 TI - Inhibition of platelet aggregation by isosorbide dinitrate. PMID- 2875643 TI - Drug interaction studies and encainide use in renal and hepatic impairment. AB - The effect of encainide administration on steady-state plasma digoxin levels was evaluated in 17 patients receiving stable doses of digoxin. A paired t test, comparing plasma digoxin levels (mean +/- standard error) before encainide therapy (1.05 +/- 0.14 ng/ml) and after 2 weeks of encainide, 100 mg/day (1.03 +/ 0.11 ng/ml) or 200 mg/day (1.2 +/- 0.2 ng/ml), indicates no significant (p greater than 0.05) change in digoxin levels. These results were confirmed in a second study of 10 patients with severe congestive heart failure. Also, no difference in efficacy of either drug was observed and changes in dosing of digoxin were not required. Plasma concentrations of encainide and its 2 major metabolites, O-demethyl encainide (ODE) and 3-methoxy-O-demethyl encainide, significantly increased by 31.6%, 43.1% and 35.6% after concomitant cimetidine administration in 13 healthy adult men receiving 75 mg/day of encainide. However, a retrospective evaluation of 33 patients receiving both drugs did not reveal any clinically significant interactions. Retrospective evaluation of patients enrolled in clinical studies who received concomitant digoxin (268), antiarrhythmics (118), anticoagulants (78), antidiabetics (40), antipsychotics (23), beta blockers (88), calcium-channel blockers (24) or diuretics (229) did not reveal any clinically significant interactions with encainide. Similarly, in vitro protein binding studies did not reveal any clinically significant interactions with encainide or its major metabolites. Six patients with moderate to severe renal impairment (creatinine clearance 10 to 38 ml/min) received 25 mg of encainide, 3 times/day, for 7 doses. Plasma encainide, ODE and 3-methoxy-O demethyl concentrations were similar to those observed in normal subjects who had received twice the dose of encainide, and steady-state apparent oral clearance of encainide was reduced by 66% with renal impairment. Based on these data it is recommended that in patients with moderate to severe renal impairment encainide be initiated at one-third the normal dose, or 25 mg once a day. Doses may be elevated in small increments at 1-week intervals if needed for efficacy. The effect of hepatic impairment on the pharmacokinetics of encainide was studied in 7 patients with clinically documented cirrhosis. Compared with normal subjects studied using a similar protocol, the plasma concentrations of encainide were elevated significantly due to a 6-fold decrease in oral clearance. However, since plasma concentrations of the active metabolite ODE were correspondingly lower, specific encainide dosing instructions for patients with hepatic impairment are not indicated. PMID- 2875645 TI - Does dietary linolenic acid influence blood pressure? AB - Short-term intervention studies have shown that diets rich in polyunsaturated fats have hypotensive properties. We have studied the long-term effects of dietary fat on blood pressure (BP) using adipose-tissue, fatty acid composition analysis in 399 free-living male subjects (average age, 47 yr). Stepwise regression analysis showed that adipose linoleic acid (18:2 n-6) was not associated with BP, whereas an absolute 1% increase in linolenic acid (18:3 n-3) was associated with a decrease of 5 mm Hg in the systolic, diastolic, and composite mean arterial BP. Linolenic acid (18:3) comprised only one-eighth the amount of linoleic acid (18:2)--the major polyunsaturate in adipose tissue and hence in the diet (2% vs 16%)--and yet it had a disproportionate association with BP. This may be related to its role as a precursor for the production of prostaglandins and/or other vasoregulators. Dietary manipulation with n-3 fatty acids may be helpful in the treatment and prevention of hypertension. PMID- 2875646 TI - Rapid detection of cross-linked fibrin degradation products in plasma using monoclonal antibody-coated latex particles. AB - Conformational and structural changes on conversion of fibrinogen to fibrin and its cross-linking by Factor XIIIa lead to the development of new antigenic determinants that permit differentiation between their plasminolytic cleavage products. A monoclonal antibody (DD-3B6/22) that is specific for cross-linked fibrin derivatives containing the D dimer configuration has been used in developing a latex agglutination procedure that can detect fibrin degradation products in either plasma or serum. Fibrinogen or its degradation products do not cross-react with this antibody. Results were calibrated with an enzyme immunoassay, which used a purified D dimer standard. Plasmas from 40 normal subjects, all having D dimer levels below 250 ng/mL measured by enzyme immunoassay, were all negative by latex assay. In contrast, positive latex agglutination titers were obtained with 87 of 88 patients with demonstrated deep venous thrombosis, pulmonary embolism, or disseminated intravascular coagulation. Compared to enzyme immunoassay, latex agglutination assay is less sensitive, but this latex procedure provides a rapid and less elaborate test for elevated levels of cross-linked fibrin degradation products in patients with thrombosis. Plasma assays for fibrin degradation products are preferable to those using serum. PMID- 2875647 TI - Controversial approaches to treating learning disabilities and attention deficit disorder. AB - It is estimated that between 3% and 7% of children and adolescents in this country--up to 4 million--are learning disabled. Of this group, about 20% also have attention deficit disorder. Many professionals in multiple disciplines have proposed treatment approaches. When research has been done to support the approach, the reports and data may be published in journals not normally read by the practicing physician. When research data are not available, the information may be in a popular book, newspapers, or lay magazines or on television. Thus, parents may know of ideas and suggestions before the professional in clinical practice. These acceptable and controversial approaches to treatment are reviewed. It is understandable that a parent would seek out improved ways of helping his or her child. I reviewed the significant literature in an effort to assist the practicing physician in providing appropriate parental guidance and clinical interventions. PMID- 2875648 TI - Thyrotropin binding inhibitor immunoglobulin. Its pathogenetic importance in hypothyroidism. AB - Two patients with hypothyroidism had detectable serum levels of thyrotropin binding inhibitor immunoglobulin (TBII). Patient 1 was a newborn infant who had transient neonatal hypothyroidism due to transfer of TBII from the mother with nongoitrous autoimmune thyroiditis. Patient 2 was an 8-year-old girl with Down's syndrome who presented with signs of myxedema and central precocious puberty. She had no goiter, and the recognition of thyroid disease was delayed; the histological diagnosis of chronic lymphocytic thyroiditis was established by aspiration biopsy, and TBII had strong thyroid adenyl cyclase-inhibiting activity in vitro. It appears that TBII may be pathogenetically important for occurrence of neonatal hypothyroidism and nongoitrous autoimmune thyroiditis without goiter. PMID- 2875649 TI - Healing of chronic Barrett ulcers with omeprazole. AB - Three patients with a long-standing benign Barrett ulcer, resistant to treatment with high doses of either cimetidine or ranitidine, given for at least 3 months, were treated with 40 mg omeprazole daily for 9 wk. After 2 wk all symptoms had disappeared and at the end of treatment all three patients showed complete endoscopic ulcer healing. Patient compliance was excellent and no side effects were registered. We conclude that omeprazole is effective and safe in healing chronic resistant Barrett ulcers. PMID- 2875650 TI - Pulmonary infiltrates and eosinophilia in a young man. PMID- 2875651 TI - The hemodynamic and clinical responses to terazosin, a new alpha blocking agent, in congestive heart failure. AB - To determine the hemodynamic effects of a new alpha 1 blocker, terazosin, in congestive heart failure, six patients with this condition underwent hemodynamic testing (at rest and during exercise) before and after dosing. Doses of 2, 5, and 10 mg were examined in sequence over 3 days to define dose-response characteristics. Terazosin, in these doses, decreased pulmonary and systemic vascular resistances and right atrial and pulmonary capillary wedge pressures. Terazosin increased stroke volume and cardiac output, presumably through afterload-reduction, without altering heart rate. These aforementioned responses were apparent both at rest and during exercise. While a direct relationship existed between dose and plasma concentration, a similar relationship was not observed for dose (or plasma concentration) and hemodynamic response; no differences were noted between the hemodynamic responses to the three doses. Improvement in hemodynamics persisted and the clinical status and exercise capacity improved in the four patients chronically treated (over 2 months) with terazosin. Treating the heightened tone of the sympathetic nervous system in congestive heart failure with the alpha 1 blocker, terazosin, may be of benefit to some patients afflicted with this disorder. PMID- 2875652 TI - Insulin-enhanced thermogenesis in skeletal muscle after exercise: regulatory factors. AB - Insulin increases O2 consumption by 25-30% in perfused rat muscle following intense exercise. The object of the present study was to characterize further the basis for this finding. Toward this end, O2 consumption was measured in the perfused hindquarter of rats either following a treadmill run or muscle contractions induced by electrical stimulations of the sciatic nerve. The results indicate that the increase in O2 consumption induced by insulin varies with the intensity of exercise, that it is initiated by factors generated locally rather than systemically, and that it is not attenuated by alpha or beta-adrenergic blockade. The results also demonstrated that the increase in O2 consumption is substantially diminished if glucose is not added to the perfusion medium. PMID- 2875653 TI - Beta-adrenergic agonists increase amplitude of LH release in orchidectomized rats. AB - The role of intravenously (iv) injected adrenergic agonists in the pulsatile secretion of luteinizing hormone (LH) was examined in unanesthesized, freely behaving, castrated male rats. The alpha 2-adrenergic receptor agonist, clonidine (25 micrograms/kg), and the alpha 1-adrenergic agonist, (-)-phenylephrine (12.5 micrograms/kg), did not significantly alter pulsatile release of LH. The physiological beta 2-adrenergic receptor agonist, (-)-epinephrine (2.5 micrograms/kg), significantly increased the mean plasma concentrations of plasma LH and the amplitude of the LH pulses over a period of 70 min. The specific beta 2-receptor agonist, salmefamol, significantly increased the mean plasma concentrations of LH and especially the average amplitude of LH pulses over 70-80 min in a dose-related fashion following the injection of doses from 25 to 125 micrograms/kg. The frequency of LH pulses was not significantly increased by either agonist at any of the doses employed. Salmefamol-induced increases in plasma LH could be prevented by the beta-adrenergic blocker, bornaprolol (FM-24), in a dose-related manner. When injected together with synthetic LH-releasing hormone (400 ng/kg), salmefamol (125 micrograms/kg) significantly increased the mean plasma concentrations of LH over 70 min compared with values in controls receiving LH-releasing hormone only. The data support the concept that beta agonists act on their receptors in the pituitary to facilitate LH-releasing hormone-induced discharge of LH. PMID- 2875654 TI - Acylcarnitines: drug absorption-enhancing agents in the gastrointestinal tract. AB - Acylcarnitines were tested as potential absorption-enhancing agents for drugs that are poorly absorbed from the gastrointestinal tract. Urethan-anesthetized Sprague-Dawley rats and conscious Beagle dogs were used. Palmitoyl-DL-carnitine was the most effective acylcarnitine tested, although significant increases in drug absorption were observed with acylcarnitines containing C12 through C18 fatty acid chains. Palmitoyl-DL-carnitine afforded significant increases in the absorption of cefoxitin, gentamicin, cytarabine, somatostatin analogue, and alpha methyldopa. The response to palmitoyl-DL-carnitine was concentration dependent and reversible within 60-120 min. Histological examination of the intestinal tissue revealed no apparent change in mucosal structural integrity at doses of palmitoyl-DL-carnitine that resulted in increased drug absorption. The acylcarnitines were effective in increasing drug absorption from the small intestine and the rectal compartment of both rats and dogs. The data also demonstrated effectiveness with aqueous and solid dosage forms (Witepsol H-15 suppositories). The data suggest that acylcarnitines may be effective and safe absorption-enhancing agents for a variety of drugs. PMID- 2875655 TI - Transport and hydrolysis of glucagon in the proximal nephron. AB - Transport and hydrolysis of glucagon in the rabbit proximal nephron were studied. Iodinated glucagon (0.34 +/- 0.02 pg/nl, mean +/- SE) was microperfused (16.0 +/- 1.1 nl/min) in vitro through proximal straight nephron segments for 30 min. Radiolabeled material, primarily 125I-tyrosine, appeared in the bathing medium in a linear fashion as a function of time (0.406 pg glucagon X mm tubule length-1 X min-1). Hydrolysis of glucagon by proximal tubule homogenates was pH dependent, with a large peak of activity observed at pH 7.0-7.4 and a smaller one at pH 3.0. Analytical cell fractionation studies of proximal tubule cells revealed glucagon hydrolyzing activity associated with the brush border and cytosol at pH 7.4. Less than 3% of activity was found associated with the contraluminal membrane. Substantial catabolism was observed at lysosomes on lowering the pH to 5.0. Incubation of glucagon directly in the presence of isolated renal cortical microvilli confirmed the presence of a high-capacity glucagon-degrading hydrolase. In addition to glucagon-hydrolyzing activity associated with the proximal nephron, noncortical activity was observed that was not accounted for by proximal tubule hydrolases. The data suggest several mechanisms for renal extraction of glucagon, including hydrolysis by enzymes at the brush border of the proximal tubule, prior to reabsorption of metabolites there. Conversely, enzymes associated with the contraluminal membrane of the proximal nephron probably contribute little to its hydrolysis. Nonproximal extracortical degradation of glucagon may account for its previously observed peritubular hydrolysis. PMID- 2875656 TI - Meclofenamate potentiates vasoreactivity to alpha-adrenergic stimulation in chronically hypoxic guinea pigs. AB - The aim of this study was to examine the effect of chronic hypoxia on systemic vascular reactivity and the role of prostaglandins in modulating the vascular response to chronic hypoxia. Meclofenamate, a prostaglandin synthesis inhibitor, increased the systemic vascular resistance response to the alpha-adrenergic agonist, phenylephrine, in awake, unrestrained guinea pigs exposed for 6 wk to high altitude (3,900 m), but it did not alter the response in animals kept at low altitude (1,600 m). The systemic vascular resistance response to phenylephrine before treatment with meclofenamate was the same in high- and low-altitude animals. Meclofenamate also increased the contractile response to phenylephrine in aortic rings isolated from high- but not low-altitude animals. The systemic vascular resistance response to angiotensin II was the same in high- and low altitude animals, and meclofenamate increased this response to the same extent in both groups. Thus chronic hypoxia appeared to enhance vascular production of dilator prostaglandins during beta-adrenergic stimulation. PMID- 2875657 TI - O2 consumption during exercise in dogs--roles of splenic contraction and alpha adrenergic vasoconstriction. AB - To examine the influence of alpha-adrenergic vasoconstriction on the aerobic capacity of dogs, we calculated O2 consumption (VO2) by the Fick method during submaximal and maximal exertion before and during alpha-adrenergic blockade with phentolamine. Regional blood flow was measured with radioactive microspheres. alpha-Adrenergic receptor blockade reduced VO2 by 12.9% during submaximal and 17.9% during maximal exercise. Arterial and venous lactic acid approximately doubled during both levels of stress in the presence of alpha-adrenergic receptor blockade. Calculated VO2 decreased because arteriovenous O2 (A-V)O2 extraction was reduced by 11.6% during submaximal exercise. During maximal exercise a 16.7% decrease in (A-V)O2 extraction and a 5.7% decrease in cardiac output contributed to the decrease in maximal VO2. During both levels of stress, (A-V)O2 extraction was reduced because arterial O2 content was decreased. Since circulating hematocrits during exercise were reduced by alpha-adrenergic receptor blockade (43-38%), we postulate that splenic contraction likely was inhibited. Additionally, distribution of blood flow to skeletal muscle and visceral organs was unaltered by alpha-blockade. To examine the importance of splenic contraction during maximal exercise, we examined hemodynamic and metabolic responses before and after splenectomy. Compared with the spleen-intact condition, splenectomized dogs demonstrated a 12.6% reduction in VO2 as a result of 7.7 and 5.5% reductions in (A-V)O2 extraction and cardiac output, respectively. (A-V)O2 extraction was reduced because arterial O2 content and circulating hematocrit during exercise were decreased. Therefore, in the exercising dog, alpha-adrenergic receptor blockade reduces O2 consumption and causes a shift to anaerobic metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875658 TI - Reactive dilation and late-hyperemic constriction of epicardial coronary artery after short coronary occlusion. AB - Coronary blood flow and epicardial coronary artery diameter were simultaneously measured by an electromagnetic or Doppler flow probe and a pair of ultrasonic crystals, respectively, during reactive hyperemia in conscious dogs. Reactive dilation appeared after the full appearance of reactive hyperemia and lasted for a period of 4-20 times the duration of the coronary occlusion. beta-Receptor blockade (propranolol, 1 mg/kg iv) attenuated both the reactive hyperemia in volume by 21-22% (P less than 0.01) and dilative responses of the epicardial coronary diameter by 27-28% (P less than 0.01), despite a nonsignificant attenuation of the resting or peak hyperemic coronary blood flow. When coronary blood flow was held constant during reperfusion, by an occluder distal to the ultrasonic crystals, the reactive dilation disappeared. A peculiar reactive constriction was noted when coronary occlusion was performed proximal to the site of the ultrasonic crystals. Appearance of this constriction was at 149 and 385 s after the release of 5 and 60 s of coronary occlusion, respectively. This late reactive constriction disappeared after pretreatment with alpha- (phentolamine, 1 mg/kg iv) and/or alpha- + beta-blockade, but not with beta-blockade alone, and it was not observed when the coronary diameter was measured proximal to the occluder. Thus reactive dilation of the epicardial coronary artery derives from an increase in coronary flow and is reduced by propranolol via a reduction in the hyperemic flow, suggesting a flow-dependent change in the diameter of the epicardial coronary artery. Reactive constriction is a local phenomenon following marked reduction in the coronary diameter and is abolished by alpha-adrenergic blockade with phentolamine. PMID- 2875659 TI - Effects of calcium entry blockade on left ventricular dynamics in exercising dogs. AB - To study the previously undefined effects of calcium entry blockade on left ventricular (LV) function and coronary blood flow during dynamic exercise we gave intravenous equihypotensive infusions of nifedipine (10 +/- 4 SE micrograms X kg 1 X min-1), diltiazem (60 +/- 8 micrograms X kg-1 X min-1), and verapamil (52 +/- 7 micrograms X kg-1 X min-1) before and after intravenous propranolol (2 mg/kg) to chronically instrumented dogs at rest and while running on a treadmill at 4 and 10 km/h. Prior to beta-blockade, each agent significantly and equivalently (P = NS among drugs) reduced mean arterial pressure during exercise (-13% nifedipine, -8% diltiazem, -15% verapamil at 4 km/h, each P less than or equal to 0.01 vs. exercise alone) but did not significantly alter LV end-diastolic dimension (EDD), heart rate, or cardiac output compared with exercise alone. Only verapamil blunted the positive inotropic response to exercise (LV dP/dtmax decreased 20% at 4 km/h, P less than 0.01 vs. exercise alone). Coronary blood flow was significantly and equivalently increased at rest and during submaximal exercise with each calcium blocker, but this effect was largely offset by propranolol. During exercise after beta-blockade each agent produced significant additional reductions in mean arterial pressure and dP/dtmax at peak exercise but did not alter LVEDD or heart rate compared with results obtained with propranolol alone. Combined beta-blockade and verapamil uniquely diminished myocardial contractility to a greater extent at peak exercise than at rest (dP/dtmax 1,260 +/- 410 peak exercise vs. 1,775 +/- 431 mmHg/s rest, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875660 TI - Pressor resistance to vasopressin in sodium depletion, potassium depletion, and cirrhosis. AB - Resistance to the pressor effects of angiotensin II, but not norepinephrine, has been observed in sodium depletion, potassium depletion, and cirrhosis. We tested the response to arginine vasopressin (AVP) in each of these conditions. Male Sprague-Dawley rats were made sodium depleted with furosemide and a low-sodium diet for 3 days, potassium depleted by feeding a low-potassium diet for 14-21 days, or cirrhotic by inhalation of carbon tetrachloride for 8 wk. In conscious rats, the pressor response to graded doses of AVP was reduced in sodium depletion by 27-43% compared with control rats. Sodium-depleted rats were also found to have enhanced baroreceptor reflexes, since the decrease in heart rate for a given increase in mean arterial pressure was greater than in control rats. When the ganglionic blocker pentolinium tartrate was given to sodium-depleted rats the pressor response to AVP was restored to control levels. In potassium-depleted rats the pressor response to AVP was 21-52% lower than that in controls, whereas cirrhotic rats also had a blunted response to AVP (14-41% lower than control). However, there was no evidence in either of these two states of enhanced baroreceptor activity, and pretreatment with pentolinium tartrate did not restore the pressor response to normal. Therefore, although resistance to the pressor effect of AVP was found in all three conditions, the mechanism of this effect was different in sodium depletion compared with potassium depletion and cirrhosis. We conclude that resistance to the pressor action of AVP in sodium depletion was secondary to resetting of the baroreceptors. PMID- 2875661 TI - Alpha 1-adrenergic receptor activation depolarizes rat supraoptic neurosecretory neurons in vitro. AB - Intracellular data were obtained from 35 supraoptic nucleus neurosecretory neurons maintained in vitro in intra-arterially perfused explants of rat hypothalamus. Addition of norepinephrine, phenylephrine, or methoxamine, but not isoproterenol (30-200 microM), consistently induced membrane depolarization, bursting activity, and an associated prolongation in action potential duration, effects that were reversibly antagonized by the alpha 1-antagonist prazosin. Norepinephrine-evoked depolarizations demonstrated no consistent change in membrane resistance and were reduced both by membrane hyperpolarization and by raising extracellular K+. Norepinephrine shortened the time course of spike hyperpolarizing afterpotentials and increased the magnitude of late depolarizing afterpotentials. It is proposed that one of norepinephrine's actions on supraoptic neurons involves K+ channels, perhaps by modulation of a transient K+ current known as A current. PMID- 2875662 TI - Hallucinations: theoretical and clinical overview. AB - The authors review the literature on hallucinations; provide theoretical background on these phenomena from physiological, biochemical, and psychological points of view; and discuss the presentations of hallucinations in different diagnostic categories. The longstanding notion that hallucinations are to be equated with schizophrenia, they conclude, is clearly unfounded, and hallucinations are never pathognomonic of any given disorder but can be relatively specific for some conditions. Current knowledge and methods of research have produced no single mechanism to account for the etiology or pathogenesis of hallucinations. The authors present an integrated approach toward viewing the etiology and clinical presentation of hallucinations that involves concepts of biological vulnerability and psychological influences. PMID- 2875663 TI - Outcome study of first-episode psychosis. I: Relapse rates after 1 year. AB - One-year relapse rates were assessed in a group of 64 patients diagnosed by Research Diagnostic Criteria who were hospitalized for their first psychotic episode. Life-table analysis showed that of the 51 remitted patients, 71.4% of the schizophrenic patients (N = 20), 71.4% of patients with affective disorders (N = 10), and 77.8% of patients diagnosed as having either unspecified functional psychosis or other psychiatric disorder (N = 7) remained in remission at 1-year follow-up. Factors associated with relapse or poor outcome (patients who remained in episode) included no maintenance medication, longer duration of illness, and premorbid asociality. PMID- 2875664 TI - An unusual cluster of tardive dyskinesia in schizophrenia: association with cognitive dysfunction and negative symptoms. AB - Factors associated with the emergence or nonemergence of involuntary movements (tardive dyskinesia) during long-term neuroleptic treatment were investigated in an atypical, isolated population of 31 schizophrenic inpatients with an unusually high prevalence of this syndrome. Patients with involuntary movements could not be distinguished from those without such movements by general characteristics or conventional indices of neuroleptic or anticholinergic treatment. However, they were more likely to show either marked cognitive dysfunction or muteness. These findings support the proposal that, at least in schizophrenia, subtle organic changes may contribute to vulnerability to the emergence of involuntary movements. PMID- 2875665 TI - Exacerbation of schizophrenia associated with amantadine. AB - Administration of amantadine was associated with psychotic decompensations in two schizophrenic patients being maintained on concomitant neuroleptic medication. Despite a postulated dopaminergic mechanism, there seems to have been only one previous report of amantadine's precipitating psychosis in a schizophrenic patient. PMID- 2875666 TI - Neuroleptic-induced tics in two hyperactive children. AB - Two hyperactive boys who had developed motor and phonic tics during stimulant treatment reacted similarly to low doses of haloperidol and thioridazine. Neuroleptic-induced tics may be a consequence of presynaptic dopamine blockade. PMID- 2875667 TI - Clonidine therapy in withdrawal from high-dose alprazolam treatment. PMID- 2875668 TI - Carbamazepine in the treatment of tardive dyskinesia. PMID- 2875669 TI - Restructuring the health care labor force. The rise of the multiskilled allied health practitioner. PMID- 2875670 TI - Multiple competency. Its time is here. PMID- 2875671 TI - Nature of existing multiple competency programs. PMID- 2875673 TI - [Equivalence of oral and intramuscular premedication. III. Effect of premedication on anesthesia and postoperative pain]. AB - 600 patients were given 6 different premedications in randomised design to study their effect on the course of anaesthesia and on postoperative pain. Premedication acts indirectly on anaesthesia, depending on the influence of the drug on anxiety and on the somatic correlates of anxiety. The greater the sedative-anxiolytic effect of the premedication, the easier it is to induce anaesthesia, and the more superficial the anaesthesia, resulting in earlier and stronger onset of postoperative pain. On the other hand, the more anxious the patient is, the more he consumes anaesthetic drugs, whereas anaesthesia remains superficial with the same consequences in respect of postoperative pain. In view of postoperative pain, fast and early awakening from anaesthesia must not be aimed at, particularly after operations which definitely result in postoperative pain (long-term operations in those regions of the body that cannot be immobilised). PMID- 2875672 TI - Identification of alcohol abuse and alcoholism with biological parameters. AB - The prevalence and incidence of heavy alcohol consumption are major problems which have been increasing in many countries in recent years. It is crucial for physicians to consistently identify early drinking problems as well as the various end disease states in order to minimize suffering and maximize recovery. This paper reviews the evolutionary development of clinical tools for detection of alcohol abuse. The focus is primarily on clinical/biochemical indicators of alcohol abuse, emphasizing but not limited to changes in hematological characteristics, liver enzyme activity, lipids, immune function factors, hormones, neurological factors, and some physically based tests. Use of test combinations and sophisticated statistical analysis of pattern changes in test batteries evidence increased diagnostic efficiency. PMID- 2875674 TI - Pupil response to alfentanil and fentanyl. A study in patients anaesthetised with halothane. AB - The pupillary response to alfentanil, fentanyl and a saline placebo was measured in patients anaesthetised in a standard manner with halothane, to determine whether the pupil diameters changed in a way which could be distinguished from background activity. Measurements were made to the nearest 0.1 mm using a purpose built pupillometer. The response to the drugs can be clearly distinguished from the background activity seen in the placebo group. The time courses of constriction caused by the two drugs are significantly different from the placebo group responses. The time to maximum to response with alfentanil is 4 minutes compared with 8 minutes for fentanyl. Both drugs produced at least 35% reduction in mean pupil diameter compared with the placebo group. The duration of the response to alfentanil was 25 minutes, whereas the fentanyl response lasted more than one hour. PMID- 2875675 TI - Anaesthetic management of Takayasu's arteritis. AB - A case of type IV Takayasu's arteritis in whom a renal autotransplant was performed is presented. Extensive cardiovascular measurements were made, which enabled the assessment of vascular responsiveness to various anaesthetic manipulations. The management of the condition is discussed and certain recommendations made in light of the experience gained. PMID- 2875676 TI - Oral lormetazepam in premedication. A comparison with diazepam. AB - Lormetazepam, a relatively new benzodiazepine was compared in a randomised, double blind trial with diazepam for its effectiveness as an oral premedicant drug. A scoring system was used to assess sedation, relief of anxiety, nausea, dizziness and cardiovascular effects in two groups of patients having orthopaedic operations. Some statistical indication that lormetazepam has a greater anxiolytic effect than diazepam was found, but in assessing total effect using a known scoring system, no difference was demonstrated between the two drugs. PMID- 2875677 TI - Time course of actions of combinations of muscle relaxant drugs. PMID- 2875678 TI - Pharmacokinetics and pharmacodynamics of alfentanil infusions during general anesthesia. AB - The pharmacokinetic and pharmacodynamic properties of alfentanil were studied in 64 surgical patients. Alfentanil was administered as a loading infusion (25-130 micrograms/kg) followed by a maintenance infusion (0.25-1.3 micrograms X kg-1 X min-1) as part of a nitrous oxide-narcotic-muscle relaxant technique. Although alfentanil doses of at least 50 micrograms/kg (in combination with thiopental, 2 mg/kg) were required to prevent hemodynamic changes during intubation, apnea or chest wall rigidity frequently occurred with alfentanil loading infusions exceeding 75 micrograms/kg. The alfentanil clearance rate was significantly lower in patients with liver dysfunction (2.3 +/- 1.3 vs 4.2 +/- 2.0 ml X kg-1 X min-1, mean +/- SD). In addition, the patients who required opioid antagonists to reverse postoperative respiratory depression had lower clearance rates (1.5 +/- 0.7 vs 4.1 +/- 1.9 ml X kg-1 X min-1) and longer elimination half-life values (406 +/- 304 vs 87 +/- 53 min). For maintenance of hemodynamic stability during superficial and intraabdominal operations, alfentanil serum concentration response curves revealed ED95 values exceeding 300 ng/ml and 400 ng/ml, respectively. Our study also demonstrated a wide range of clinical responses to fixed doses of alfentanil. At equivalent doses, some patients required supplemental anesthetics, whereas others required an opioid antagonist. Careful titration of the alfentanil maintenance infusion is recommended to minimize the possibility of postoperative respiratory depression. PMID- 2875679 TI - The influence of hepatic plasma flow on alfentanil plasma concentration plateaus achieved with an infusion model in humans: measurement of alfentanil hepatic extraction coefficient. AB - In a group of seven patients undergoing intracranial surgery under neurolept anesthesia, an alfentanil infusion was initiated with a loading dose of 235 micrograms/kg over 5 min, followed by a maintenance infusion rate of 1.8 microgram X kg-1 X min-1 in order to obtain a steady state plasma concentration (Css) of 400 ng/ml-1 according to an infusion model. The mean values of Css (446 +/- 209 ng/ml) were close to the predicted ones. Nevertheless, an important intersubject variability in Css values was observed. A positive linear correlation existed between alfentanil steady state clearance and indocyanine green clearance (r = 0.88) and between alfentanil steady state clearance and cardiac index (r = 0.93). In three patients, a catheter was inserted into an hepatic vein to determine the alfentanil hepatic extraction coefficient. Alfentanil plasma clearance did not differ from alfentanil hepatic clearance and alfentanil hepatic extraction coefficient values ranged from 0.32-0.53. We conclude that alfentanil is a drug with an intermediate hepatic extraction coefficient and that alfentanil plasma clearance depends on hepatic plasma flow, which is thus one of the factors accounting for individual variability in plasma concentration plateaus achieved with an infusion model. PMID- 2875680 TI - A pharmacokinetic explanation for increasing recovery time following larger or repeated doses of nondepolarizing muscle relaxants. AB - The authors used pharmacokinetic and pharmacodynamic modeling to explain the time course of neuromuscular blockade following single or multiple doses of three nondepolarizing muscle relaxants. Published and unpublished pharmacokinetic and pharmacodynamic data for 13 normal subjects were used to simulate the duration of neuromuscular blockade (time from administration of the muscle relaxant to 25% recovery of control twitch tension) following six successive doses of atracurium (150-400 micrograms/kg initially, followed by 100 micrograms/kg), vecuronium, or pancuronium (30-80 micrograms/kg initially, followed by 20 micrograms/kg). With atracurium, duration of action was similar for the second and sixth doses, regardless of the initial dose. With vecuronium (initial doses of 30-80 micrograms/kg) and pancuronium (initial doses of 30-60 micrograms/kg), duration of action was longer after the sixth dose than after the second; with larger initial doses of pancuronium (70 and 80 micrograms/kg), duration of action was similar following the second and sixth doses. The authors also determined two recovery times (time for twitch tension to recover from 5-25% and from 25-75% of control value) for varying single doses of atracurium, vecuronium, or pancuronium. When the dose of atracurium was increased from 200 to 400 micrograms/kg, neither recovery time increased. When the dose of vecuronium was increased from 40 to 80 micrograms/kg, 5-25% recovery time increased from 6.0 +/- 2.5 min to 8.8 +/- 4.0 min (mean +/- SD) and 25-75% recovery time increased from 8.7 +/- 4.3 min to 12.6 +/- 4.4 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875681 TI - [Effect of neurovegetative inhibition on immunologic indices of oncosurgical patients]. PMID- 2875682 TI - [Goals, components and criteria of the adequacy of premedication]. PMID- 2875683 TI - Clinicopathologic study of horses surviving pyrrolizidine alkaloid (Senecio vulgaris) toxicosis. AB - Twenty horses of various ages had inadvertently ingested alfalfa hay contaminated with Senecio vulgaris. Among them, 4 died of liver disease. Blood was collected from affected horses at monthly intervals for 7 months and at the 9th and 14th months. The following serum enzymes and chemical items were assayed: aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, gamma-glutamyl transferase, sorbitol dehydrogenase, total bilirubin, BUN, glucose, cholesterol, inorganic phosphate, calcium, total protein, and albumin. Amino acid profiles, conjugated bile acids, sulfobromophthalein clearance times, and liver histopathologic changes via serial biopsies were also monitored. Liver histopathologic changes revealed lesions progressively increasing in severity. Aspartate aminotransferase and plasma amino acid ratios indicated chronic liver degeneration (0.05 level of significance). gamma-Glutamyl transferase and lactate dehydrogenase as well as BUN values fluctuated, but returned to within reference values. Horses appeared clinically normal 14 months after intoxication, but were unable to tolerate stress of exercise. PMID- 2875684 TI - [Asthmatic bronchitis]. PMID- 2875685 TI - [Evaluation of the biological activity of avermectin against mosquitoes]. PMID- 2875686 TI - [Erythema nodosum in hemorrhagic rectocolitis and Crohn's disease]. AB - Erythema nodosum (EN) has been reported in patients with ulcerative colitis (UC) since 1909. The reported incidence varies from 0.9 p. 100 to 18.9 p. 100. A wide range of incidence of EN has also been found in Crohn's disease (CD), with figures varying from 0.7 p. 100 to 8 p. 100 (fig. 1). Different criteria for the diagnosis of EN, UC and CD probably account for the scattering of values. A review of 324 cases of inflammatory bowel diseases revealed 21 cases with one or more episodes of EN: 6 out of 195 cases of UC (3.1 p. 100) and 15 out of 129 cases of CD (11.6 p. 100). The incidence was higher in females (5.7 p. 100 in UC, 17.5 p. 100 in CD) than in males (0 in UC, 6.9 p. 100 in CD). At the time of the eruption, patients with CD were younger (mean 24.3 years) then those with UC (mean 37.5 years). The interval between the onset of the intestinal symptoms and the nodular eruption was shorter in patients with CD (2.6 years) than in those with UC (8.2 years). The inflammatory bowel disease (whether UC or CD) started earlier in patients with EN than in EN-free patients. EN antedated the onset of intestinal manifestations in one patient with UC. In the remaining 20 patients the intestinal symptoms came first. EN was often recurrent, and the 21 patients suffered 32 episodes at varying intervals. One patient had 4 and another 3 episodes; six patients had 2 and 13 had one single episode. Three patients with UC had 2 episodes and 5 patients with CD had 2 or more episodes. The morphology and distribution of the lesions was fairly classical, except in 2 patients who had only 1 and 2 nodules respectively on one leg. The eruption subsided in all cases within 2 to 5 weeks, and no atrophy, suppuration or ulceration was observed. Most episodes of EN occurred during active phases of the intestinal disease. This was not so, however, in 2 cases in which the eruption followed an acute streptococcal throat infection. EN was more often found in total UC than in the less extensive distal and rectal types (Table I). It was also more frequent in the ileocolic form than in the exclusively ileal and colonic forms (Table II).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2875687 TI - Hepatic metabolism of dietary alpha-linolenic acid in suckling rats, and its possible importance in polyunsaturated fatty acid uptake by the brain. AB - The presence of large amounts of long chain-polyunsaturated fatty acids (PUFA) in the brain implies an exogenous intake of unsaturated fatty acids, either as essential fatty acids, or in the form of higher homologues resulting from hepatic metabolism. To determine the influence of the diet upon the potential availability of polyunsaturated fatty acids to the brain, four different diets were used with comparable amounts of 18:2 n-6, but variable amounts of 18:3 n-3 (0.2, 1, 2 and 9%). These diets were administered to female rats from the day of mating and during the periods of gestation and lactation. Fifteen days after birth suckling animals were killed and the fatty acid distribution was studied in the serum in two lipoprotein classes (VLDL-LDL and HDL). On the whole, an increase in dietary 18:3 n-3 resulted in an increase of polyunsaturated fatty acids of the n-3 series and a decrease in fatty acids of the n-6 series. The modification chiefly concerned the terminal fatty acids in each series (22:5 n-6 and 22:6 n-3). It is noteworthy that the influence of exogenous 18:3 n-3 upon the 20:4 n-6 content of lipoproteins was not significant below 2% of 18:3 n-3 intake, a level that we have previously shown to be both necessary and sufficient to satisfy the requirements of the brain for fatty acids of the n-3 series. In the liver, the intermediary metabolism ensures an important release of long-chain polyunsaturated fatty acids, which may help to satisfy the lipid requirements of the brain. PMID- 2875688 TI - Polyglutamation of the antifolate anticancer drug N10-propargyl-5,8-dideazafolic acid (CB 3717) in the mouse. AB - The antifolate drug N10-propargyl-5,8-dideazafolic acid was shown to be metabolized to its gamma-glutamyl conjugates in mouse liver and kidneys after administration at a dose of 20 mg/kg. The tissue levels of both CB 3717 and its polyglutamates were time dependent. However, in liver the clearance of polyglutamated conjugates was 10 times slower than that of the parent compound. In liver after 48 hr up to 50% of recovered radioactivity consisted of CB 3717 polyglutamates. In addition to polyglutamate derivatives, in both liver and kidney, 72 hr after CB 3717 administration another minor CB 3717 metabolite(s), unsusceptible to conjugase treatment, was detected. The nature of this metabolite(s) is currently unknown. PMID- 2875690 TI - Dual regulation of adenylate cyclase and guanylate cyclase: alpha 2-adrenergic signal transduction in adrenocortical carcinoma cells. AB - Isolated adrenocortical carcinoma cells of rat contain alpha 2- and beta adrenergic receptors. When these cells are incubated with alpha 2-adrenergic agonists, there is a concentration-dependent increase of cyclic GMP that is blocked by the alpha 2-adrenergic antagonist yohimbine but not by the beta antagonist propranolol. Concomitantly, both p-aminoclonidine (20 microM) and clonidine (100 microM), the alpha 2-adrenergic agonists, stimulate membrane guanylate cyclase activity. In calcium free medium there is no alpha 2-agonist dependent increase in cyclic GMP. Isoproterenol, a beta-agonist, and forskolin cause an increase in cyclic AMP but not cyclic GMP. The cyclic AMP increase induced by isoproterenol is blocked by propranolol but not by yohimbine. Isoproterenol- and forskolin-dependent increases in cyclic AMP are inhibited by p aminoclonidine and the inhibition is relieved by yohimbine. These results indicate a dual regulation of guanylate cyclase and adenylate cyclase by the alpha 2-receptor signal: guanylate cyclase is coupled to the receptor in a positive fashion, whereas adenylate cyclase is coupled in a negative fashion. Calcium is obligatory in the cyclic GMP-mediated response. PMID- 2875689 TI - Transglutaminase modification of rhodopsin in retinal rod outer segment disk membranes. AB - Rhodopsin in rod outer segment disk membranes was enzymatically modified by erythrocyte transglutaminase, which linked small primary amines to glutamine residues. In order to avoid formation of protein crosslinks, rhodopsin was first reductively methylated to modify its lysines. From 1.9 to 2.5 mol of putrescine, ethanolamine, or dinitrophenylcadaverine were incorporated into rhodopsin by transglutaminase during 16 h reaction time. A maximum of 3.5 mol of [14C]putrescine was incorporated per mole of rhodopsin during 48 h. Essentially all of the rhodopsin sequence containing the putrescine could be removed by limited proteolysis of the membranes by thermolysin. Glutamine residues in positions 236, 237, 238, and 344 were modified to approximately equal extents, as determined by isolation of the cyanogen bromide peptides of modified rhodopsin followed by further subdigestion of the peptides. The modified glutamine residues are located in the helix V-VI (or F1-F2) connecting loop and in the carboxyl terminal region of rhodopsin. PMID- 2875691 TI - Field studies on the surveillance of Coquillettidia crassipes (Van der Wulp) and the isolation of a strain of Cardiofilaria in peninsular Malaysia. AB - Surveillance methods for Coquillettidia crassipes were studied in an open housing estate near Kuala Lumpur using three types of traps Trinidad 10 trap, modified Lard can trap and IMR trap, each baited with chicken or pigeon. All traps attracted Cq. crassipes. There was no significant difference in the catches in the three traps. There was also no significant difference between chicken and pigeon as bait. Catches at heights of 1.5, 3, 4.5 and 6 m did not show any significant difference in density. Cq. crassipes was active at night with an early peak during the first hour of the night and a minor peak between 0100 and 0200 hours. The activity of the parous and nulliparous sections of the population was similar, except that a higher proportion of the parous females was active during the second peak compared with the nulliparous females. The parous rate was 22.3%, and the probability of survival through one day for two gonotrophic cycles was 0.711 and 0.650. The infection rate for Cardiofilaria was 29 out of 1052 (2.76%) and the infective rate (L3 larvae) was 13 out of 1052 (1.24%). 48.3% of the infected Cq. crassipes had a worm burden of more than ten larvae. One of the chickens in the traps was positive for microfilariae of Cardiofilaria four weeks after exposure as bait. Laboratory bred Cq. crassipes fed on this chicken produced infective larvae in ten days, and these were inoculated into clean chickens and pigeons. Microfilariae appeared in the chickens but not in pigeons. The adult worms recovered await identification. PMID- 2875692 TI - Plasma neuroleptic levels in the elderly patients on propericiazine therapy- possible role of morbidity. AB - Plasma neuroleptic levels of 31 elderly psychiatric patients (8 males and 23 females, age 80.1 +/- 8.95 years) on chronic propericiazine therapy and with multimorbidity were measured by means of radioreceptor assay. There was no significant correlation between the daily dose and the plasma neuroleptic level. Nor was there any significant correlation between the patients' age and the ratio of plasma neuroleptic level to the daily dose. On the other hand, the immobility score of patients (GBS scale) had a high correlation with the ratio of the plasma neuroleptic level to the daily dose. Furthermore, patients with positive C reactive protein (CRP) had an average ratio value 3-fold higher than the CRP negative group. The results suggest that the plasma neuroleptic level of propericiazine in elderly patients is raised by morbidity and immobility rather than chronological age per se. PMID- 2875694 TI - The effects of alpha-2 agonists and antagonists on gastric acid secretion. AB - The effects of alpha-2 agonists clonidine, xylazine and guanabenz as well as those of alpha-2 antagonists tolazoline and yohimbine on gastric acid secretion were investigated in Shay rats, Schild rats and isolated guinea-pig gastric fundus. In Shay rats clonidine, xylazine and guanabenz displayed marked antisecretory effects, whereas tolazoline and yohimbine had no effect. Under the same conditions, yohimbine fully prevented the actions of clonidine, xylazine and guanabenz, while tolazoline showed partial antagonism. In Schild rats both clonidine and xylazine displayed a stimulant secretory action, but guanabenz was without effect; cimetidine fully prevented the excitatory effects of clonidine and xylazine. Both tolazoline and yohimbine increased gastric acid secretion in Schild rats: the effect of tolazoline was inhibited by cimetidine, while the effect of yohimbine was prevented by pirenzepine or vagotomy. On isolated guinea pig gastric fundus, clonidine, xylazine and tolazoline exerted a stimulatory activity, whereas guanabenz and yohimbine had no effect: these excitatory responses were fully prevented by cimetidine. Overall results indicate that clonidine and xylazine have both inhibitory and excitatory effects on gastric acid secretion, while guanabenz produces only inhibitory effects. The inhibitory activity appears to be mediated by activation of presynaptic alpha-2 receptors on the vagus nerve, whereas the excitatory effects seem to be mediated by histaminergic pathway. The stimulant secretory action of tolazoline may be due to its imidazoline-like structure allowing interaction with histamine H2-receptors: accordingly, this effect is lacking for guanabenz, which is structurally unrelated to imidazoline. The excitatory effect of yohimbine appears to be exerted on central cholinergic sites, as indicated by its disappearance in vagotomized rats. PMID- 2875693 TI - Gastric antisecretory and pharmacologic properties of N,N-dimethyl-N'-(2 diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyridyl)ur ea (L-634,366). AB - N,N-Dimethyl-N'-(2-diisopropylaminoethyl)-N-(4,6-dimethyl-2-pyridyl)urea (L 634,366) was selected from a series of pyridylurea compounds with antisecretory activity as a potential therapeutic agent for the treatment of ulcer disease. L 634,366 was an effective inhibitor of gastric secretion evoked by gastrin, histamine and 2-desoxy-D-glucose (2-DG) in conscious dogs. Orally, L-634,366 was slightly less potent than the reference H2 receptor blocker, cimetidine as an inhibitor of secretion evoked by histamine, but was equipotent as an inhibitor of secretion evoked by gastrin and 2-DG. In vitro L-634,366 was a weak antagonist of histamine (H2) receptor responses in the guinea-pig atria and rat uterus; in the atria the antagonism appeared to be noncompetitive. In the anesthetized dog, L 634,366 possessed weak anticholinergic activity as compared to atropine in reducing vagally mediated cardiovascular, antral motor responses and with regard to antagonizing the pressor response to the muscarinic stimulant, McN 343-A. The anticholinergic activity of L-634,366 was lower and more selective than that of pirenzepine or atropine in producing mydriasis in mice, in antagonizing acetylcholine induced bradycardia in guinea-pig atria, methacholine and acetylcholine elicited contractions in the guinea-pig ileum and QNB binding to muscarinic receptors. L-634,366, like carbenoxolone, increased incorporation of 3H-glucosamine in gastric mucous indicating an increase in synthesis or turnover of mucous. L-634,366 is a novel compound possessing a broad spectrum of antisecretory activity; in vitro studies suggested a weak noncompetitive inhibition of the histamine-H2 receptor in atria. PMID- 2875695 TI - Pharmacological profile of etintidine, a new histamine H2-receptor antagonist. AB - Etintidine is a potent competitive antagonist of histamine H2-receptors. It is 4.6 and 2.2 times more potent than cimetidine in the isolated guinea pig atrium (pA2 = 7.18) and the isolated rabbit parietal cell (pA2 = 6.51), respectively. Etintidine is 2.0 (ED50 = 1.8 mg/kg, i.g.) times more potent than cimetidine at inhibiting betazole-stimulated total acid output in the chronic gastric fistula dog. In the 4 hr pylorus-ligated rat etintidine is a potent inhibitor of total acid output (ED50 = 22 mg/kg, i.d.), total pepsin output, and is well absorbed from the gastrointestinal tract. Additional pharmacological and biochemical studies indicate that etintidine displays minimal competition with appropriate ligands for the alpha 1, alpha 2, cholinergic and neuroleptic receptors in vitro, and has minimal effects on the immunological, autonomic and central nervous systems at doses much higher than antisecretory doses. While high doses of both cimetidine and etintidine increase serum prolactin levels in rats, the effect of etintidine is less than that of cimetidine. Similarly, the prolongation of hexobarbital-induced sleep time in rats is less than with cimetidine. These data indicate that etintidine may be potentially useful and safe in the treatment of peptic ulcer disease and may offer some advantages over cimetidine in terms of less potential for side effects. PMID- 2875696 TI - Coexistence of sporadic multiple endocrine neoplasia and scapular ectopic breast. Coincidence or biologically associated? AB - We describe a patient who presented with sporadic pheochromocytoma and parathyroid adenoma in the absence of medullary thyroid carcinoma, which coexisted with fully developed scapular ectopic breast tissue. If not coincidental, this association might support the concept that all components of multiple endocrine neoplasia type IIA originate from embryonic ectodermal tissue, and that sporadic multiple endocrine neoplasia type IIA, as well as ectopic breast tissue, may result from a noxious event at a critical embryonic stage. PMID- 2875697 TI - [Malignant neuroleptic syndrome: a review]. PMID- 2875698 TI - [Fast diagnosis of whooping cough in the infant. Contribution of the immunofluorescence technic]. AB - Clinical and biochemical data of 22 children admitted from May 1982 to May 1983 were reviewed to study their values for early diagnosis of pertussis. Direct immunofluorescence for Bordetella pertussis was positive in 9 of the 12 confirmed cases and seems to be a reliable test. PMID- 2875699 TI - [Psychotropic drugs and breast feeding]. PMID- 2875700 TI - Delusional depression: tricyclic response. PMID- 2875701 TI - Neuroleptic-induced extrapyramidal symptoms with fever. Heterogeneity of the 'neuroleptic malignant syndrome'. AB - From 39 reported cases of the "neuroleptic malignant syndrome," three groups were identified: those with concurrent medical problems that could cause fever that accompanied the extrapyramidal symptoms; those with medical problems less clearly related to fever; and those without other medical disorders. Dehydration, infection, pulmonary embolus, and rhabdomyolysis were the common complications of untreated extrapyramidal symptoms. Three patients died, all with medical complications. In 14 cases, no medical cause of fever was identified. Hypotheses about mechanisms for fever include psychiatric illness, disruption of dopaminergic aspects of thermoregulation, and peripheral and central effects on muscle contraction leading to excess heat production. Neuroleptic-induced rigidity should be treated vigorously, with prompt discontinuation of neuroleptic therapy and administration of dopamine agonists in severe cases with or without fever. The cases of extrapyramidal symptoms with fever are too heterogeneous to justify the assumption of a unitary and "malignant" syndrome. PMID- 2875702 TI - Response of thyrotropin to thyrotropin-releasing hormone as predictor of treatment outcome. Prediction of recovery and relapse in treatment with antidepressants and neuroleptics. AB - We determined whether the response of thyrotropin (TSH) to thyrotropin-releasing hormone could predict the outcome of treatment with antidepressant and neuroleptic drugs. We studied 114 female patients diagnosed as having major and minor depressive, manic, schizoaffective, and schizophrenic disorders. A blunted TSH response (less than 5 microU/mL [less than 5 mU/L]) at admission was associated with recovery after nine weeks of inpatient treatment using clomipramine hydrochloride for depression and haloperidol for psychosis. A blunted TSH response at discharge was associated with early relapse in depressives receiving clomipramine maintenance therapy. Our findings support the notion that the thyrotropin-releasing hormone test is a "state" marker that may be of use in predicting the outcome of treatment with antidepressant and neuroleptic drugs. PMID- 2875703 TI - Monitoring the optimal infusion of intravenous lipids. Detection of essential fatty acid deficiency. AB - Since increased amounts of the trienoic acid C20:3w9 are produced in patients with essential fatty acid (EFA) deficiency (EFAD) of the linoleic (w6) family, the trienoic (C20:3w9)-to-tetraenoic (C20:4w6) fatty acid ratio (T/T ratio) is used as a biochemical indicator of w6 EFAD. A T/T ratio above 0.02 is suggestive of w6 EFAD. Fatty acid profiles, listing the percent of individual and families of fatty acids, are useful in evaluating the effects of intravenous lipid infusions during treatment. We evaluated the condition of a patient with fat malabsorption treated with a soybean oil-based intravenous lipid solution and found that levels of linoleic acid and its derivatives did not reach reference levels, while linolenic acid and its derivatives quickly exceeded reference levels. A persistently elevated T/T ratio suggested that altered fatty acid metabolism characteristic of linoleic acid deficiency was not corrected by the treatment. Plasma levels of the EFA, ie, linoleic and linolenic acids, cannot be predicted from the lipid treatment or from the patient's clinical course; therefore, periodic measurements of EFA are required to monitor the effects of therapy. To provide the most effective therapy, the amounts and proportions of linoleic and linolenic acids provided in the intravenous infusions should be varied, as indicated by periodic monitoring of the fatty acid profile. PMID- 2875704 TI - On the approaches to a correct assessment of intracellular inclusions in Bordetella pertussis by means of electron microscopy. PMID- 2875705 TI - An electron microscope survey of the surface structures and hydrophobicity of oral and non-oral species of the bacterial genus Bacteroides. AB - Seventeen strains of Bacteroides representing 10 species were examined by negative staining; the majority were from the mouth but a few non-oral strains were included. Seven species had peritrichously-arranged, non-flagellar appendages which could be divided by morphology and ultrastructure into two subgroups, fibrils and fimbriae. Bacteroides asaccharolyticus strains B536 and B537 and Bacteroides gingivalis strains W50, W83, WPH15 and WPH35 had fimbriae with mean width of 4.4 nm and 0.5 to 6.0 microns long depending on the strain. The fimbrial length within each strain also varied. Fibrils were present on two fresh oral isolates of Bacteroides melaninogenicus, Bacteroides intermedius strains T588 and W09, Bacteroides corporis ATCC 33547, Bacteroides oralis ATCC 33269 and Bacteroides buccae ATCC 33574. Fibrils consistently clumped into bundles of variable thickness and formed a fringe around the cell periphery, ranging from 0.27 to 1.2 microns long depending on the strain. Fibril lengths of each strain were uniform. Fibrils had no measurable width and the clumps tapered towards the free ends. Bacteroides loeschii VPI 9085, Bacteroides pentosaceus strains NP333 and J1 and Bacteroides capillosus 29799 had no detectable surface appendages. Fimbriate strains had a layer outside the outer membrane, with a mean thickness of between 17.8 and 28.6 nm. Both fibrillar and fimbriate strains produced many small membranous vesicles budding from the outer membrane. There were two morphological forms of vesicles, ones with either fimbriae or fibrils (species-dependent) and ones with no attached appendages. Of eleven strains tested for cell-surface hydrophobicity by partitioning between hexadecane and buffer, all but one was non-hydrophobic. PMID- 2875706 TI - Calcium levels in rat submandibular gland and saliva after sympathetic nerve stimulation in the presence of alpha, beta 1 and beta 2-adrenergic antagonists. AB - Calcium concentration was reduced by 51 per cent compared with unstimulated contralateral glands after 60-min of electrical stimulation to the sympathetic nerve. When the alpha-adrenergic antagonists, phentolamine or phenoxybenzamine, were given 20 min before stimulation, the decrease in glandular calcium concentration (45-47 per cent) was similar to that after nerve stimulation alone; with the selective beta 2-adrenergic antagonist added to the phentolamine, the percentage decrease was similar to that found after phentolamine and sympathetic nerve stimulation only. When atenolol, a beta 1-adrenergic antagonist, was given with phentolamine, there was no secretion after subsequent nerve stimulation, nor was calcium concentration different from that of unstimulated glands. When propranolol (3 mg/kg, body wt), or atenolol + butoxamine (3 mg/kg, body wt), was given prior to stimulation there was a decrease of 21-22 per cent in gland calcium concentration. Calcium concentration of nerve-stimulated saliva was nearly 6 m-equiv./l, and twice as high with phentolamine prior to stimulation; for butoxamine together with phentolamine the change was similar to that with phentolamine alone. When beta-adrenergic antagonists were given prior to nerve stimulation, concentration of the saliva was either unchanged (propranolol) from that with nerve stimulation alone or somewhat decreased (atenolol + butoxamine). Thus sympathetic stimulation results in activation of alpha and beta 1 adrenoceptors; calcium secretion is principally regulated by the beta adrenoceptors, and beta 1-receptors have the principal role. PMID- 2875707 TI - Extracapsular cataract extraction and posterior chamber lens implantation in eyes with preexisting glaucoma. AB - Fifty eyes of 40 patients with glaucoma underwent extracapsular cataract extraction with posterior chamber lens implantation. Their visual results and early postoperative complications were compared with those of eyes in an age matched group of patients without glaucoma after the same procedure. Substantial increases in early postoperative intraocular pressure (IOP) occurred in 62% of the glaucomatous eyes and in only 10% of the normal eyes. The level of best visual acuity was slightly worse (20/40) on average in the glaucomatous eyes than in the nonglaucomatous eyes (20/25). At six months after surgery, 82.5% of the nonfiltered glaucomatous eyes needed the same number of or additional glaucoma medications to maintain an IOP of less than 20 mm Hg. Ten of the glaucomatous eyes underwent trabeculectomy along with cataract surgery due to inadequate IOP control while the patient was receiving maximum medical therapy. Control was substantially improved, with 100% of these patients receiving the same number of or fewer medications at six months. By one year, only 30% of these patients required the same number of medications postoperatively as preoperatively, but all had IOP control. PMID- 2875708 TI - The drug treatment of duodenal ulcer: physiological considerations in the choice of therapy. PMID- 2875709 TI - Ultrasonography and the impalpable testis. AB - The accuracy of inguinal ultrasonography in the pre-operative localization of the maldescended testis was assessed in 51 patients with 57 maldescended testes. Pre operative sonographic results were compared with the clinical assessment and the operative findings. Testes located in the inguinal canal or at the internal ring, which were occasionally impalpable, were readily demonstrated by sonography. The management of children with an impalpable maldescended testis should include a sonographic examination as the investigative procedure of choice. PMID- 2875711 TI - The subunit structure of methylmalonyl-CoA mutase from Propionibacterium shermanii. AB - 5'-Deoxyadenosylcobalamin-dependent methylmalonyl-CoA mutase was purified to homogeneity from Propionibacterium shermanii by a simplified procedure. The native enzyme has an apparent Mr of 165,000, similar to the enzyme from other sources but larger than previously reported. It consists of two non-identical subunits, of Mr 79,000 and 67,000 respectively. The smaller subunit is apparently not a proteolytic fragment of the larger one. The final preparation usually contained some inactive mutase, bearing a tenaciously bound cobalamin species. This protein proved to be readily separable from apoenzyme by fast protein liquid chromatography on anion-exchange columns. PMID- 2875712 TI - Characterization of dipeptidyl peptidase IV from lymphocytes of chronic lymphocytic leukemia of T-type. AB - Dipeptidyl peptidase IV was enriched about 2000-fold from lymphocytes of chronic lymphocytic leukemia of T-type. The purification procedure involved immunoaffinity chromatography using antibodies raised with highly purified dipeptidyl peptidase IV from human placenta. The lymphocytic peptidase had a subunit Mr of 110,000. Its kinetic properties were similar to those of the placenta enzyme: Two N-terminal dipeptides were cleaved from substance P and from casomorphin, and naphthylamine was released from X-prolynaphthylamides with Km values of about 0.02 mM. The lymphocytic peptidase was 10-fold less sensitive to zinc inhibition as compared to the placenta enzyme. Isoelectric focussing patterns of dipeptidyl peptidase IV in leukemic lymphocytes and in normal T lymphocytes were very similar. PMID- 2875710 TI - Properties of the branched-chain 2-hydroxy acid/2-oxo acid shuttle in mouse spermatozoa. AB - Operation of the branched-chain 2-hydroxy acid/2-oxo acid shuttle for the transfer of reducing equivalents in mitochondria of mouse spermatozoa was studied in vitro in reconstituted systems. Results show that the branched-chain 2-oxo acids within the mitochondria are offered several metabolic pathways. (a) Decarboxylation: mouse sperm mitochondria possess high branched-chain 2-oxo acid decarboxylase activity. (b) Recycling to the cytosol by using a transport system which can be inhibited by alpha-cyano-3-hydroxycinnamate and pH 6.8. (c) Transamination to the corresponding amino acids: experiments presented indicate that leucine formed from 4-methyl-2-oxopentanoate may pass to the external phase, re-initiating the cycle. These two last possibilities would allow autocatalytic operation of the shuttle. The branched-chain 2-hydroxy acids apparently do not utilize the monocarboxylate carrier to penetrate the mitochondria. PMID- 2875713 TI - Processing of pro-colipase and trypsinogen by pancreatic dipeptidyl peptidase IV. AB - Purified dipeptidyl peptidase IV from porcine pancreas or from human placenta cleaves N-terminal dipeptides from two proteins of the pancreatic juice, namely trypsinogen and pro-colipase. Phenylalanyl-proline is very effectively released (Km approximately 50 microM) from bovine or porcine trypsinogen. Both purified dipeptidyl peptidases also rapidly cleave valyl-proline from the N-terminus of porcine pro-colipase. This degradation does not increase the colipase activity of the precursor. However, under certain conditions, which are not fully understandable at present, dipeptidyl peptidase IV releases more slowly a second dipeptide, aspartyl-proline, from pro-colipase, and this results in a partial activation. Dipeptidyl peptidase IV apparently lines the excretory ducts of porcine pancreas and, therefore, is in close contact to the proteins of pancreatic juice in vivo. The possible significance of these degradations is discussed. PMID- 2875714 TI - [Action of [3,14-L-selenocysteine, 8-D-tryptophan]-somatostatin on insulin and glucagon secretion of the isolated perfused pancrease of the Wistar rat]. AB - By isolated perfused pancreas of Wistar rats the glucose (11 mmol/l) and arginine (10 mmol/l) stimulated insulin (IRI) and glucagon (IRG) secretion was measured in order to investigate the inhibitory activities of somatostatin-14 (SS 14) and the somatostatin analogue [3,14-L-seleno-cysteine, 8-D-tryptophan]-somatostatin (SeSS). SS-14 or SeSS (152.8 nmol/l) inhibit the glucose stimulated IRI secretion by 75 and 65%, respectively. Only the second phase of the biphasic arginine stimulated insulin secretion pattern by 40%. SeSS has under these conditions no effect, whereas 58 nmol/l SS-14 or SeSS show a suppressing effect on the first (20 and 55%, respectively) and second phase (65 and 85%, respectively) of the insulin secretion. Using 5.8 nmol/l SS-14 or SeSS the arginine stimulated IRG secretion was inhibited only in the second phase of the biphasic glucagon secretion pattern by about 40%. 58 nmol/l SS-14 or SeSS show an inhibiting effect on the first and on the second phase of secretion, in both cases about 50%. It is concluded that in the SS-14 molecule the sulfur of cysteine in position 3 and 14 can be exchanged by selenium without modifying the biological activities measured in the glucose or arginine stimulated IRI and IRG secretion in vitro. The D-Trp8 in the SeSS analogue does not show the typical better inhibitory action of D-Trp8 SS-14 on insulin and glucagon secretion compared with SS-14. Possibly the selenium in the SeSS analogue abolishes this effect. PMID- 2875715 TI - [Negative inotropic reflex effects in the dog ventricle before and after beta receptor blockade]. AB - Myocardial contractility of the rabbit ventricle, expressed as contractility index KI = d log (p - p0)/dtmax, was altered by both aortic nerve reflex stimulation and by beta-receptor blockade with propranolol (Obsidan) and talinolol (Cordanum, (+)-Cordanum and (-)-Cordanum). In every case, beta-receptor blockade decreased negative reflex inotropy, whereas reflex hypotension was only reduced by Obsidan. The mean reflex inotropy was 11.8% after Obsidan application and 17.3% after Cordanum injection, the reflex hypotension 28.0% and 34.8%. From the results it is concluded that Cordanum acts in the rabbit ventricle cardioselectively. If neural and pharmacological effects are related to initial effects, we may conclude that the contractile state maintained by the resting sympathetic tone is diminished. The overall reduction of KI by Cordanum blockade and reflex inhibition amounts to 45.5%, that of blood pressure to 42%. Its optical isomers act also cardioselectively, the inotropic effects, however, are smaller than those of the racemate. Obviously, reflex stimulation and beta 1 blocking agents have a similar mode of inotropic action. From this we suggest that reflex inotropy is mediated by sympathetic nerve fibres and beta 1 adrenergic receptors. PMID- 2875716 TI - Beta-adrenergic binding is increased by melatonin and alpha-adrenergic compounds. AB - Binding of the beta-adrenergic ligands [3H]dihydroalprenolol and [125I]cyanopindolol to pineal particulate fractions was increased 1- to 3.5-fold by addition of low concentrations of melatonin, alpha-adrenergic agonists, or alpha-adrenergic antagonists. Minimum concentrations of melatonin or alpha adrenergic compounds which increased beta-adrenergic binding were between 1 pM and 0.1 nM. The increased binding of [3H]dihydroalprenolol caused by melatonin (0.1 muM) was attributed to a major increase in Bmax, which persisted in protein fractions after removal of melatonin. Melatonin enhancement of [3H]dihydroalprenolol binding was apparent after 5 to 7 min (30(0], was was optimal between 20 and 40 min, and decreased at longer times. Alpha-Adrenergic receptors are unchanged during beta-receptor enhancement. PMID- 2875717 TI - Postnatal development of amino acid metabolism enzymes in the liver and muscle of 'cafeteria' rats. AB - The effect of feeding a high-energy highly palatable cafeteria diet on the liver and muscle ontogenesis of serine dehydratase, alanine transaminase, glutamine synthetase and adenylate deaminase during postnatal development of the rat has been studied. The results are in agreement with the lower amino acid utilization in cafeteria rats, both adults and during postnatal development. The feeding of excess energy coupled with high-quality protein resulted in changes in the ontogenesis of the studied enzymes that coincide with the development of protein synthesis and overall pup growth even before they had direct access to this rich diet, suggesting that cafeteria feeding already affects the amino acid metabolism of the pup through the dam's milk. PMID- 2875718 TI - Effects of phospholipases C on the beta-receptor-adenylate cyclase system of chick erythrocyte membranes. AB - The beta-adrenergic receptor located in chick erythrocyte membranes was characterized using (-)-[3H]-dihydroalprenolol ([3H]-DHA) with rapid filtration techniques. The affinity of beta-adrenergic antagonist, (-)-propranolol, was approximately 100-fold higher than that of (+)-propranolol. Catecholamines were bound with the receptor in the following order, (-)-isoproterenol greater than ( )-norepinephrine greater than (-)-epinephrine, suggested the binding site to be beta 1-classification. When the membrane preparation was treated with phosphatidylcholine-hydrolyzing phospholipase C (PCase) of Clostridium perfringens or phosphatidylinositol-specific phospholipase C (PIase) of Bacillus thuringiensis, [3H]-DHA binding was decreased to the level of 66 or 86% of the control, respectively. The treatment with sphingomyelinase C (SMase) of Bacillus cereus, however, did not cause any appreciable reduction of [3H]-DHA binding. Throughout these experiments, the equilibrium dissociation constant (KD) of [3H] DHA was not influenced by phospholipases C. The affinity of isoproterenol for beta-receptor was decreased in the absence of GTP, but not altered in the presence of GTP by PIase action. Treatment with PCase or SMase, however, did not affect the affinity of isoproterenol for beta-receptor. Treatment with PIase inhibited basal, isoproterenol-stimulated and forskolin-stimulated adenylate cyclase activities. On the other hand, PCase treatment inhibited only isoproterenol-stimulated adenylate cyclase activity, but not basal and forskolin stimulated activities. These results suggest that membrane phospholipids, especially phosphatidylcholine (PC) and phosphatidylinositol (PI), are directly related to the receptor binding and that PI interacts with adenylate cyclase activity. PMID- 2875719 TI - Intracellular recording during magnetic field application to monitor neurotransmitter release events: methods and preliminary results. AB - A method for simultaneous magnetic field application and intracellular recording is presented. A little used method for magnetic field application was exploited; the field generator consisted of a flat copper sheet through which current was passed to generate a magnetic field. The resultant magnetic field was relatively homogeneous, exhibiting a variation of +/- 5%. This compact, current-sheet field generator was mounted on the condensor of a microscope. The current induced in the intracellular electrode was reduced by injecting current equal and opposite to the induced current into the microelectrode. This step reduces the possibility of cellular effects and voltage artifacts due to the induced electrode current. The technique was used to conduct preliminary studies on the effects of extremely low frequency (ELF) linearly and circularly polarized magnetic fields (1.0 Gauss, 60 and 70 Hz) on miniature end plate potential (mepp) frequency (frequency of neurotransmitter release events) of rat flexor digitorum brevis muscle. The same synapse was utilized for both the sham-exposed control and the exposed experimental halves of an experiment. After 10 min of exposure to a 60-Hz linear field, mepp frequency was significantly increased by 12%, but exposure to a 60-Hz circular field did not significantly alter mepp frequency. Exposure to a 70-Hz linear field did not significantly change mepp frequency, but application of a 70 Hz circular field appears to decrease mepp frequency by 4%. These results indicate that both types of magnetic fields can alter mepp frequency, depending upon the frequency and configuration of the field. PMID- 2875720 TI - Eosinophilic vasculitic neuropathy in the Churg-Strauss syndrome. PMID- 2875721 TI - [Poisonings with tricyclic antidepressive agents and phenothiazines and their therapy with physostigmine]. PMID- 2875722 TI - Monitoring alcoholism treatment: the appropriateness of choice between gamma GT or MCV evaluation after a short time of abstinence. AB - Gamma glutamyl transferase (gamma GT) and mean corpuscular volume (MCV) were evaluated in 58 alcoholics entering alcoholism treatment. The same patients were reassessed after one month of abstinence. Group results revealed a significant reduction of gamma GT from 80.2 to 43.1 IU/l while no alteration was detected for MCV (from 97.1 to 96.7 mu 3). However, individual analysis showed that the average MCV results obtained from the 2nd evaluation masked important within individual differences. Thus, although a considerable percentage of alcoholics with initial high values showed an improvement, 44% of those with initial normal results had abnormally high reevaluation values. Limitations of serial MCV measurement during alcoholism treatment follow-up are discussed in light of these data. PMID- 2875723 TI - Electrophysiological actions of somatostatin on the atrioventricular junction in sinus rhythm and reentry tachycardia. AB - Because somatostatin, a neuroregulatory peptide, is found in abundance in the atria and atrioventricular node, its electrophysiological and antiarrhythmic properties were compared with those of verapamil in ten patients with paroxysmal atrioventricular tachycardia. During sinus rhythm, intravenous somatostatin slowed the heart rate whereas verapamil increased it. Though both agents prolonged atrioventricular conduction time and refractoriness, verapamil was more potent. They were equally effective at terminating reentry atrioventricular tachycardia, restoring sinus rhythm in six of seven patients. Whereas verapamil consistently blocked conduction in the atrioventricular node, somatostatin usually induced ventricular extrasystoles at the time of conversion. Somatostatin may have physiological importance in the neurohumoral control of cardiac impulse formation and conduction. PMID- 2875724 TI - Pharmacokinetics and pharmacodynamics of vecuronium in patients with cholestasis. AB - The pharmacokinetics and pharmacodynamics of vecuronium were studied in nine surgical patients with cholestasis, and in 14 patients without hepatic or renal disease. After the administration of vecuronium 0.2 mg kg-1 the plasma concentration of vecuronium and the degree of neuromuscular blockade were measured. The plasma clearance of vecuronium was decreased significantly (P less than 0.01) from 4.30 +/- 1.56 ml min-1 kg-1 (mean +/- SD) in normal patients to 2.36 +/- 0.80 ml min-1 kg-1 in patients with cholestasis. The elimination half life was of 58 +/- 22 min in normal patients and was prolonged to 98 +/- 57 min (P less than 0.05) in patients with cholestasis. The total apparent volume of distribution was unchanged in patients with cholestasis. A prolonged neuromuscular blockade induced by vecuronium was observed in patients with cholestasis: the duration of effect from injection to 75% recovery of the twitch height was prolonged from 74 +/- 19 min in normal patients to 111 +/- 13 min in patients with cholestasis. The plasma concentration corresponding to 50% recovery from paralysis did not differ significantly between the two groups. Vecuronium has a prolonged effect in patients with cholestasis which is caused by a delay in its elimination. PMID- 2875725 TI - Hepatobiliary disposition of vecuronium bromide in man. AB - The plasma and bile concentrations, the biliary excretion and the neuromuscular blocking effect of vecuronium bromide were studied during surgery in 13 patients who had received 150 micrograms kg-1 i.v. The amount of vecuronium in liver biopsies taken after i.v injection was measured in a separate group of six patients. Vecuronium appeared early in the bile, in concentrations that were 30 50 times greater than those in the plasma. On the basis of the measured amount of vecuronium excreted in the bile, together with the accepted average daily bile flow, it was estimated that more than 40% of vecuronium was excreted in the bile in 24 h. Liver biopsies indicated that the liver may contain more than 50% of the i.v. dose 30 min after injection. The large distribution of vecuronium into the liver may account for the initial rapid decline in vecuronium plasma concentration and its relatively short duration of action. In this study, neuromuscular blockade was prolonged, possibly as a result of interference, by surgical manipulation, with the rapid hepatic uptake of vecuronium. PMID- 2875726 TI - Clinical pharmacology of vecuronium in children. Studies during nitrous oxide and halothane in oxygen anaesthesia. AB - Forty-seven children (ASA I or II) were studied during nitrous oxide-oxygen, halothane anaesthesia. The dose-response curve for vecuronium was determined after the injection of a single bolus (40, 55 or 70 micrograms kg-1) to 33 patients. The ED50 and ED95 were 31 and 64 micrograms kg-1 respectively. Fourteen children received a larger dose (100 micrograms kg-1); good intubating conditions were obtained in all of these within 2 min. After a single bolus (100 micrograms kg-1) the duration of action was 36.5 min and the recovery index was 9.3 min. In patients who received small maintenance doses (25 micrograms kg-1) after a single bolus (100 micrograms kg-1) the recovery index after the last maintenance dose was not increased. There were no significant changes in heart rate or arterial pressure. In children, vecuronium has a short duration of action and lacks cumulative or cardiovascular side affects. PMID- 2875727 TI - Combination therapy with beta-adrenoceptor blockers and calcium antagonists. AB - Verapamil and nifedipine enhance the hypotensive and anti-anginal effects of beta adrenoceptor blocking drugs. The combination of beta-adrenoceptor blocking drugs with nifedipine may pose fewer safety problems than the combination with verapamil especially in ischaemic heart disease when left ventricular function is suspect. Verapamil as a single agent may be as effective as a beta-adrenoceptor blocking drug in angina and provide a suitable alternative. Careful supervision is required when verapamil is combined with beta-adrenoceptor blockers for both angina and hypertension but reported clinical problems in hypertension are few. PMID- 2875728 TI - Verapamil in angina pectoris. AB - New knowledge of the pathophysiology of coronary disease has helped determine the therapy for angina pectoris. Calcium antagonists have the advantage of being direct coronary vasodilators as well as decreasing overall demand by systemic vasodilatation. Verapamil has the same anti-anginal effect during exercise as beta-adrenoceptor blockers but has the advantage of increasing rather than decreasing the cardiac output and so fatigue both at rest and exercise commonly seen with beta-adrenoceptor blockers is not found with verapamil. The longterm incidence of side-effects with verapamil are few and it can be used as a single anti-anginal therapy in a three times daily dosage. Left ventricular function where normal and near-normal is not depressed. Tolerance to therapy has not been recorded. The anti-anginal effects have been shown to remain effective over at least a 5 year period. Verapamil should be considered as initial therapy for patients with stable angina pectoris. PMID- 2875729 TI - Patterns of presentation, treatment and outcome in hepatic abscess. PMID- 2875730 TI - Structural characterization of the ATP-hydrolyzing portion of the coated vesicle proton pump. AB - The ATP-hydrolyzing portion of the proton pump from clathrin-coated vesicles (isolated from calf brain) was solubilized with three nondenaturing detergents (cholate, octyl glucoside, and Triton X-100). The hydrodynamic properties of the solubilized (Mg2+)-ATPase were then determined by sedimentation analysis in H2O and D2O and gel filtration on Sepharose 4B. The coated vesicle (Mg2+)-ATPase migrated under all conditions as a single peak of activity. In cholate, the sedimentation coefficient (S20,w), Stokes radius (a), and partial specific volume (vc) were 8.25 (+/- 0.20) S, 68 (+/- 2) A, and 0.71 (+/- 0.03) cm3/g, respectively. In octyl glucoside and Triton X-100 these values were respectively 7.90 (+/- 0.20) and 7.45 (+/- 0.20) S, 68 (+/- 3) and 101 (+/- 5) A, and 0.74 (+/ 0.03) and 0.75 (+/- 0.03) cm3/g. Application of the Svedberg equation to these data gave a molecular weight for the protein-detergent complex of 217,000 +/- 21,000 (cholate), 234,000 +/- 26,000 (octyl glucoside), and 337,000 +/- 40,000 (Triton X-100). Assuming the protein binds one micelle of detergent, these values correspond to a protein molecular weight of 215,000 +/- 21,000 (cholate), 226,000 +/- 26,000 (octyl glucoside), and 247,000 +/- 40,000 (Triton X-100). The cholate solubilized, gradient-purified (Mg2+)-ATPase, when combined with a 100,000 g pellet fraction, could be reconstituted by dialysis into phospholipid vesicles which displayed ATP-dependent proton uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875731 TI - Estimated conformation, orientation, and accumulation of dynorphin A-(1-13) tridecapeptide on the surface of neutral lipid membranes. AB - Equilibrium thermodynamic and kinetic estimations were used to confirm the rather unusual conformation, orientation, and accumulation of dynorphin A-(1-13) tridecapeptide (dynorphin1-13) on the surface of neutral lipid membranes, as observed by Erne et al. [Erne, D., Sargent, D. F., & Schwyzer, R. (1985) Biochemistry 24, 4261-4263]. I started from the premise that the most stable conformation of molecularly disperse peptides in contact with the hydrophobic phase of a membrane is helical [Henderson, R. (1979) Soc. Gen. Physiol. Ser. 33, 3-15]. Calculation of the Gibbs free energy difference for the transfer of increasing numbers m of N-terminal residues of dynorphin1-13 from their random coil conformation in water to their alpha-helical conformation in a hydrophobic phase, with the values provided by Von Heijne and Blomberg [Von Heijne, G., & Blomberg, C. (1979) Eur. J. Biochem. 97, 175-181], showed an energy minimum at m = 9 that corresponded to the observed apparent association constant of 9 X 10(4) L/mol. This confirmed our experimental observations. The orientation of dynorphin1-13 in the interphase was estimated by calculation of the molecular amphiphilic moment A. This force vector was defined in analogy to the "helical" and "structural" hydrophobic moments of Eisenberg et al. [Eisenberg, D., Weiss, R. M., & Terwilliger, T. C. (1982) Nature (London) 299, 371-374]. It takes into account the segregation of hydrophobic and hydrophilic residues with respect to the center of the alpha-helix. A peptide located in a hydrophobic-hydrophilic gradient experiences a torque that tends to orient A in a direction perpendicular to the surfaces of equal hydrophobicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875733 TI - Structure of mitochondrial F1-ATPase studied by electron microscopy and image processing. AB - The structure of soluble F1-ATPase (EC 3.6.1.3) has been investigated by computer analysis of individual molecular images extracted from electron micrographs of negatively stained particles. A total of 1241 images was interactively selected from several digitized micrographs and these images were subsequently aligned relative to different reference images. They were then submitted to a multivariate statistical classification procedure. We have focussed our attention on the main 'hexagonal' view which represents some 40% of our population of images. In this view, six masses are located on the outer region of the projection which are associated with the alpha and the beta subunits of the protein. A seventh mass is located close to the centre of the hexagon, but slightly off its exact midpoint. It has the shape of the letter V and its two legs point to two of the outer protein masses, or one alpha-beta subunit pair. The corner of the V has a density as high as those of the large subunits. Possible subunit arrangements and their consequences for the mechanism of ATP synthesis are discussed. PMID- 2875732 TI - Identification of amino acid residues photolabeled with 2-azido[alpha 32P]adenosine diphosphate in the beta subunit of beef heart mitochondrial F1 ATPase. AB - When beef heart mitochondrial F1-ATPase is photoirradiated in the presence of 2 azido[alpha-32P]adenosine diphosphate, the beta subunit of the enzyme is preferentially photolabeled [Dalbon, P., Boulay, F., & Vignais, P. V. (1985) FEBS Lett. 180, 212-218]. The site of photolabeling of the beta subunit has been explored. After cyanogen bromide cleavage of the photolabeled beta subunit, only the peptide fragment extending from Gln-293 to Met-358 was found to be labeled. This peptide was isolated and digested by trypsin or Staphylococcus aureus V8 protease. Digestion by trypsin yielded four peptides, one of which spanned residues Ala-338-Arg-356 and contained all the bound radioactivity. When trypsin was replaced by V8 protease, a single peptide spanning residues Leu-342-Met-358 was labeled. Edman degradation of the two labeled peptides showed that radioactivity was localized on the following four amino acids: Leu-342, Ile-344, Tyr-345, and Pro-346. PMID- 2875734 TI - Effect of disulfide cross-linking between alpha and delta subunits on the properties of the F1 adenosine triphosphatase of Escherichia coli. AB - Under very mild oxidizing conditions the delta subunit of the F1-ATPase of Escherichia coli can be crosslinked by a disulfide linkage to one of the alpha subunits of the enzyme. The cross-linked ATPase resembles the native enzyme in the following properties: specific activity; activation by lauryldimethylamine N oxide (LDAO); binding of aurovertin D and ADP; cross-linking products with 3,3' dithiobis(succinimidyl propionate); binding to ATPase-stripped everted membrane vesicles and the N,N'-dicyclohexylcarbodiimide sensitivity of the rebound enzyme. However, the rebound crosslinked ATPase differed from the native enzyme in lacking the ability to restore NADH oxidation - and ATP hydrolysis-dependent quenching of the fluorescence of quinacrine to ATPase-stripped membrane vesicles. It is proposed that the delta subunit is involved in the proton pathway of the ATPase, and that this pathway is affected in the alpha delta-cross-linked enzyme. The mechanism for activation of the ATPase by LDAO was examined. Evidence against the proposal of Lotscher, H.-R., De Jong, C. and Capaldi, R.A. (Biochemistry (1984) 23, 4140-4143) that activation involves displacement of the epsilon subunit from an active site on a beta subunit was obtained. PMID- 2875735 TI - Involvement of (Na+ + K+)-ATPase in binding and actions of palytoxin on human erythrocytes. AB - Palytoxin (about 1 pM) increases the permeability of human erythrocytes. We now report its radiolabeling with 125I, followed by affinity purification on porcine kidney membranes. The resulting ligand binds fast and reversibly to intact erythrocytes. The Kd from velocity and equilibrium measurements is 2 X 10(-11) M, and the number of binding sites about 200 per cell. Binding is promoted by divalent cations (Ca2+ greater than Sr2+ greater than Ba2+) and by borate. It is inhibited by K+ (IC50 2 mM), ouabain (IC50 3 X 10(-9) M) and ouabagenin (IC50 6 X 10(-6) M). Conversely, [3H]ouabain is displaced by the substances and concentrations mentioned, and also by palytoxin (Ki 3 X 10(-11) M). Dog erythrocytes, which are known to possess a very low (Na+ + K+)-ATPase activity, are resistant to and lack specific binding sites for palytoxin. Binding of 125I palytoxin, like that of [3H]ouabain, depends on the state of (Na+ + K+)-ATPase. ATP depletion decreases binding of both ligands to erythrocytes. Binding of 125I palytoxin and [3H]ouabain to red cell stroma is partially restored by ATP. In contrast to [3H]ouabain, binding of 125I-palytoxin to red cell stroma is not promoted by Mg2+ and Pi. The data show that (a) all known promoters and inhibitors of palytoxin action on human red cells do so by enhancing or decreasing its binding, (b) (Na+ + K+)-ATPase serves as a receptor for palytoxin, and (c) the antagonism by ouabain is competitive at the receptor level. They support our previous hypothesis that palytoxin increases human erythrocyte permeability by formation of pores through (Na+ + K+)-ATPase or its close vicinity. PMID- 2875736 TI - Characterization of three aminopeptidases purified from maternal serum. AB - The biochemical characteristics of aminopeptidase A (EC 3.4.11.7), oxytocinase (EC 3.4.11.3) and alanyl aminopeptidase (EC 3.4.11.2) purified from serum of pregnant women were compared. Aminopeptidase A hydrolysed only acidic amino acid derivatives, whereas oxytocinase and alanyl aminopeptidase had partially overlapping broad substrate specificities. Oxytocinase showed the highest Vmax value with LeuNA but the lowest Km value with ArgNA (Km 0.059 +/- 0.08 mmol/l). Alanyl aminopeptidase hydrolysed AlaNA most rapidly, but showed the highest affinity for LysNA (Km 0.054 +/- 0.006 mmol/l). The enzymes were sensitive to EDTA. Co2+, Ni2+ and Zn2+ were able to reactivate all suppressed enzymes, but Mn2+ reactivated only aminopeptidase A after EDTA inhibition. The alkaline earth metals were activators of aminopeptidase A, while Co2+ activated only alanyl aminopeptidase. This enzyme was the most sensitive to L-amino acids. Acidic amino acids inhibited aminopeptidase A but had no effect on the two other enzymes. Oxytocinase was most sensitive to thermal treatment. Amastatin did not inhibit oxytocinase, whereas aminopeptidase A was more resistant than alanyl aminopeptidase to this effector. PMID- 2875737 TI - Identification of subsidiary catalytic groups at the active site of beta-ketoacyl CoA thiolase by covalent modification of the protein. AB - beta-Ketoacyl-CoA thiolase (acyl-CoA:acetyl-CoA C-acyltransferase, EC 2.3.1.16) is known to possess sulfhydryl groups of cysteines at the active site that are essential for its catalytic activity. Other groups at the active site that participate in the catalytic process were identified by using anhydride reagents which covalently modify the protein by specifically reacting with any amino groups potentially present at the active site. Since these reagents may also react with thiol groups, the enzyme's amino groups were modified after masking the cysteine thiols present by an alkylalkane thiosulfonate-type reagent, methyl methanethiol-sulfonate (MMTS), that selectively formed a disulfide bridge, thus generating an inactive thiolmethylated enzyme. When this procedure was followed, the enzyme could be undoubtedly modified at its amino by the anhydride reagent, leading to a doubly modified protein. The thiomethyl group could then be removed by reduction with dithiothreitol, yielding an enzyme modified solely on the amino residues. The amino group could be unblocked in turn by exposure to acidic pH. The different anhydrides inactivated thiolase, but only acetoacetyl coenzyme A (AcAcCoA) provided any protection against inactivation. When thiolmethylcitraconyl thiolase was reduced with dithiothreitol the enzyme remained inactive, but when the doubly modified enzyme was exposed to pH 5 then the reduction led to formation of an active enzyme. These results are interpreted as demonstrating a role for an amino group at the enzyme active site. A catalytic mechanism is proposed for the enzyme which involves the amino group. PMID- 2875738 TI - Effects of dietary nutrients on substrate and effector levels of lipogenic enzymes, and lipogenesis from tritiated water in rat liver. AB - When fasted rats were refed for 4 days with a carbohydrate and protein diet, a carbohydrate diet (without protein) or a protein diet (without carbohydrate), the effects of dietary nutrients on the fatty acid synthesis from injected tritiated water, the substrate and effector levels of lipogenic enzymes and the enzyme activities were compared in the livers. In the carbohydrate diet group, although acetyl-CoA carboxylase was much induced and citrate was much increased, the activity of acetyl-CoA carboxylase extracted with phosphatase inhibitor and activated with 0.5 mM citrate was low in comparison to the carbohydrate and protein diet group. The physiological activity of acetyl-CoA carboxylase seems to be low. In the protein diet group, the concentrations of glucose 6-phosphate, acetyl-CoA and malonyl-CoA were markedly higher than in the carbohydrate and protein group, whereas the concentrations of oxaloacetate and citrate were lower. The levels of hepatic cAMP and plasma glucagon were high. The activities of acetyl-CoA carboxylase and also fatty acid synthetase were low in the protein group. By feeding fat, the citrate level was not decreased as much as the lipogenic enzyme inductions. Comparing the substrate and effector levels with the Km and Ka values, the activities of acetyl-CoA carboxylase and fatty acid synthetase could be limited by the levels. The fatty acid synthesis from tritiated water corresponded more closely to the acetyl-CoA carboxylase activity (activated 0.5 mM citrate) than to other lipogenic enzyme activities. On the other hand, neither the activities of glucose-6-phosphate dehydrogenase and malic enzyme (even though markedly lowered by diet) nor the levels of their substrates appeared to limit fatty acid synthesis of any of the dietary groups. Thus, it is suggested that under the dietary nutrient manipulation, acetyl-CoA carboxylase activity would be the first candidate of the rate-limiting factor for fatty acid synthesis with the regulations of the enzyme quantity, the substrate and effector levels and the enzyme modification. PMID- 2875739 TI - Role of lysosomotrophic reagents in glucocorticoid hormone action. AB - Administration of (10 mg/200 g) methylamine or chloroquine to adrenalectomized rats for 2 days followed by a single injection of either cortisol (2.5 mg/200 g) or dexamethasone (0.5 mg/200 g) resulted in a significant enhancement of the tyrosine aminotransferase enzymatic activity in rat liver versus rats given a single injection only of either steroid. Lysosomotrophic reagents were unable to induce tyrosine aminotransferase when administered alone. Cytosols from rat liver treated with lysosomotrophic reagents in vivo had approx. 20-30% more specific binding to [3H]dexamethasone as compared to the control, untreated rats. This enhanced binding was due to an increase in the concentration of the receptor rather than a change in the affinity of the hormone for the receptor. Rat livers perfused with and homogenized in 10 mM Tris-HCI/0.25 M sucrose buffer (pH 7.5) containing about 5 mM lysosomotrophic reagents showed optimum stabilization of the steroid unbound glucocorticoid receptor in vitro at both 4 degrees C and 25 degrees C. These reagents had no effect on in vitro transformation of [3H]dexamethasone-receptor complex or on the binding of the thermally transformed receptor to the nuclei. It is concluded from these studies that lysosomotrophic reagents enhance tyrosine aminotransferase induction by glucocorticoids and stabilize unbound glucocorticoid receptor both in vivo and in vitro without any effect on in vitro transformation of the steroid-receptor complex. PMID- 2875740 TI - [Accumulation of K+ in E. coli grown in aerobic conditions]. AB - The character of K+ accumulation in E. coli grown aerobilcally in the salt medium with succinate was studied. K+ uptake via the Trk system has Km 3.4 mM and Vmax 0.45 mM X g+1 X min-1. The initial rates of K+ uptake were not changes at different pH from 6.0 to 8.3 and temperature 17-37 degrees C. DCC did not block, protonophores and arsenate blocked the operation of Trk system. Valinomycin increased (or had no effect) K+ accumulation. K+ distribution is in good conformity with the measured membrane potential. The Trk system works at the utilization of lactic acid and glucose as well as of succinate. The Trk system is described. K+ ionophore by using the membrane potential and ATP regulates functioning of this system. PMID- 2875742 TI - EEG coherence and power in the discrimination of psychiatric disorders and medication effects. AB - Electroencephalogram (EEG) coherence (COH) and power measures were included in a series of stepwise discriminant analyses to determine which variables were most sensitive in the differentiation of four psychiatric inpatient groups and two major classes of psychotropic medication. Eight channels of eyes-closed, bipolar EEG activity were recorded from 74 inpatients (paranoid schizophrenics, dysthymics, major affectives receiving tricyclics, neuroleptics, or no medication, and geriatrics). Discriminant analyses were conducted for theta, alpha, and fast beta frequency bands for power variables, COH variables, and the resultant significant power and COH discriminating variables. Without exception, COH measures, usually in the alpha band, were more sensitive than power measures in differentiating the various groups. Results suggested that COH decreases with age, is greatest in paranoid schizophrenics, decreases with neuroleptic medication, and increases with tricyclic antidepressants. Group differences were interpreted in accordance with an arousal model for COH. PMID- 2875741 TI - Levels of growth hormone and growth-hormone-releasing factor in cord blood. AB - In order to evaluate the mechanism of high growth hormone (GH) secretion in perinatal life, the levels of GH and growth-hormone-releasing factor (GRF) in cord blood were determined. Plasma-immunoreactive GRF was measured by a double antibody RIA method. The levels (mean +/- SD) of GH, GRF and somatostatin (SRIF) were 23.4 +/- 10.2 ng/ml, 49.5 +/- 11.7 and 41.5 +/- 10.4 pg/ml, respectively; they were remarkably higher than those of healthy adults. In statistical analysis, there were no significant relationships among the levels of GH, GRF or SRIF. We speculate that a high GRF release from the hypothalamus might increase the secretion of GH in the perinatal period. PMID- 2875744 TI - Early versus late onset psychosis and tardive dyskinesia. AB - Patients with late-onset psychosis (defined as psychosis requiring hospitalization at age 45 or more, n = 20) were compared with early-onset psychosis patients (defined as psychosis requiring hospitalization at age 25 or less, n = 56) for the prevalence of tardive dyskinesia (TD). Late-onset psychosis patients were found to have significantly more TD (p less than 0.01), which was more severe (p less than 0.05) and developed in a relatively shorter period of neuroleptic treatment (p less than 0.001), than patients with early-onset psychosis. In addition, TD patients (irrespective of early or late onset of neuroleptic treatment) were found to show a preponderance of drug-free periods (p less than 0.01) in their past neuroleptic history, more so than non-TD patients. Our findings indicate that late-onset psychosis should be considered to be a risk factor for the development of TD. PMID- 2875743 TI - Influence of neuroleptics on the metabolism of tricyclic antidepressants--in vitro experiments with rat liver microsomes. AB - The influence of two neuroleptics--the phenothiazine perazine and the butyrophenone haloperidol--on the metabolism of the tricyclic antidepressants amitriptyline (AMI), imipramine (IMI), and chlorimipramine (CMI) was studied in vitro in isolated liver microsomes of female Sprague-Dawley rats. The rats were pretreated over 10 days with either NaCl solutions or with 1, 3, and 10 mg/kg haloperidol or 5 and 15 mg/kg perazine, respectively. The microsomal fraction was incubated with various concentrations of antidepressants. The drugs and their metabolites were analyzed by high-performance liquid chromatography (HPLC). Neither pretreatment with haloperidol nor perazine had any significant influence on the demethylation and N-oxidation activity of the microsomes. Benzylic 10 hydroxylation of AMI or IMI or 10- and 11-hydroxylation of CMI was inhibited significantly by pretreatment with perazine, as was 2-hydroxylation of IMI and CMI, whereas 8-hydroxylation of CMI was not influenced. The inhibition was dose dependent. With haloperidol, only the high dose of 10 mg/kg caused a significant inhibition of benzylic 10-hydroxylation, whereas phenolic hydroxylation was not influenced. The inhibition was much lower than for perazine. Comparing the results with pharmacokinetic studies in humans revealed a good agreement in metabolic pathways. The study could therefore be important in the choice of neuroleptic drugs in combination therapy. PMID- 2875745 TI - Effect of a 12-hour subcutaneous infusion of somatostatin-14 on blood glucose, insulin and glucagon levels in healthy subjects and insulin dependent diabetics. AB - We compared the influence of a 12-hour subcutaneous infusion of somatostatin-14 on glucose homeostasis in two normal subjects and two insulin-dependent diabetics (IDD). In all cases, somatostatin infusion led to a decrease of blood glucose during the first hours. The diabetogenic effect of somatostatin was confirmed in normal subjects. Postprandial blood glucose response was exaggerated in one insulin-dependent diabetic while in the other, glucose tolerance was improved. Unexpected high levels of immunoreactive somatostatin were measured in insulin dependent diabetic patients. They might be due to a decreased somatostatin catabolism. PMID- 2875746 TI - World Health Organization and International Society for Quality Assurance in Health Care. Udine, Italy, June 1985. PMID- 2875748 TI - [Effect of ascorbic acid on the binding of 3H-GABA and 3H-glutamic acid to synaptosomes of the rat cerebral cortex]. AB - The effects of different concentrations of L-ascorbic acid (Asc) on Na+-dependent binding of 3H-GABA and 3H-DL-glutamic acid to rat brain cortical synaptosomes were studied. Asc, at a concentration nearly equal to brain extracellular one (3 X 10(-4) M), had no effect on specific and nonspecific 5H-GABA binding. At higher concentrations (10(-3) M) Asc strongly inhibited, and at lower concentrations (10(-6) M) considerably stimulated 3H-GABA binding. At a concentration of 10(-5) 10(-3) M Asc tended to decrease 3H-DL-glutamic acid binding. PMID- 2875747 TI - [Isolation and partial purification of the endogenous inhibitor of receptor binding of 3H-L-glutamate]. AB - The endogenous factor that inhibited 3H-L-glutamate specific binding (FIB) was isolated from the aqueous extract of the crude mitochondrial fraction of the rat cerebral cortex homogenate and partially purified. The purification procedure involved several steps of ion-exchange, gel-permeating and thin-layer chromatography. Partially purified FIB competitively inhibited 3H-L-glutamate specific binding and had the molecular weight of 450-600 Da. Glutamic acid residues were found in FIB amino acids. The functional role of the isolated factor as an endogenous modulator involved in the regulation of effective synaptic transmission of glutamatergic brain synapses is discussed. PMID- 2875749 TI - [Molecular and cytogenetic approach to the mapping of methylated polymorphic restriction fragments of human rRNA genes]. AB - Combined restriction with Bam H I and Sal I (or Hpa II) has revealed Bam H I fragment on a non-transcribed spacer of rRNA genes in one out of four individuals under study. Using Ag-staining and hybridization in situ, chromosome 13p+ enriched by inactive rRNA gene copies was found in the given individual. Since Sal I does not restrict methylated sequences and rRNA genes are repressed by methylation, it is concluded that methylated Banm I-restricted rRNA gene fragments of non-transcribed spacer are localized in chromosome 13p+ of the individual in question. PMID- 2875750 TI - [Ultrastructural characteristics of endocrine and glandular gastric cells]. AB - Electron microscopy of human gastric mucosa has demonstrated that the endocrine cells are closely and specifically related to the adjacent glandular cells and the basal membrane. Cytoplasmic strands of the adjacent cells surround the endocrine cells and their projections, probably, regulating their secretion. The above outlined relations are considered a structural basis for complex regulatory endocrine and paracrine functions of the gastric endocrine cells. PMID- 2875751 TI - [Ultrastructure of cells of the rat entero-endocrine system during exposure to cholera toxin]. AB - Horse radish peroxidase-labelled cholera toxin (choleragen) binds to the receptors of entero-endocrine cell (Ec-cells) plasmalemma. Unlike columnar epitheliocytes, the effect of choleragen on Ec-cells. PMID- 2875752 TI - Antilymphocytic antibodies and marrow transplantation. VIII. Recipient conditioning with Clq-affine monoclonal anti-pan T antibodies prevents GVHD in homozygous fully mismatched mice. AB - An approach to suppressing secondary disease with antibodies was studied that differed from conventional antibody treatment of donor marrow in vitro. It consisted of the selection of anti-Thy-1 antibodies with high affinity for Clq, the first subunit of the complement cascade, and a single injection of such antibodies into prospective irradiated marrow recipients. Monoclonal mouse IgM and rat IgG 2c antibodies of high titers in complement-dependent test systems but with low affinity for Clq caused little immunosuppression. Monoclonal rat IgG2b or mouse IgG2a anti-Thy-1 antibodies with high affinity for Clq prevented acute and chronic mortality of graft-v-host disease (GVHD), however, when injected in irradiated CBA or AKR mice prior to C57BL/6 spleen and/or bone marrow cell transfusion. This treatment simultaneously suppressed residual host-v-graft reactivity of the irradiated mice, so that permanent hematopoietic engraftment ensued even at 5 or 6 Gy. Full chimerism and specific tolerance were obtained. Primary immune response to SRBC was clearly depressed in the chimeras; secondary immune response was not. Clearance of T cell antibody activity (greater than 6 days), timing, and dose of injected antibody, as well as other modalities of the conditioning treatment that may have contributed to the remarkable immunosuppression, are discussed. PMID- 2875753 TI - Rearrangement of the bcr gene in Philadelphia chromosome-negative chronic myeloid leukemia. AB - We studied the clinical, hematologic, cytogenetic, and molecular biologic features of seven patients with Philadelphia (Ph1) chromosome-negative chronic myeloid leukemia (CML). In five cases the hematologic findings were indistinguishable from those of patients with classical Ph1-positive disease. Myeloid cells were studied by chromosome-banding techniques. One patient had a masked Ph1 chromosome (with translocation t(4;9;22)), one had a deletion involving chromosome 16, and one had a small minority population of 22q- cells without 9q+ but otherwise normal metaphases; metaphases from the other four patients were entirely normal. DNA prepared from the myeloid cells was digested with the restriction enzymes EcoRI, HindIII, BamHI and BglII. Southern analysis using a 0.6-kb fragment of the breakpoint cluster region (bcr) gene showed the presence in each patient's DNA of a germline fragment together with a rearranged fragment or fragments with at least one of the restriction enzymes. We conclude that genomic changes in the bcr gene characteristic of CML can be present in the absence of a Ph1 chromosome. PMID- 2875754 TI - A de novo intragenic deletion of the potential EGF domain of the factor IX gene in a family with severe hemophilia B. AB - We have studied a family of three patients who were severely afflicted with hemophilia B without inhibitor for their factor IX genes through the use of factor IX cDNA and genomic DNA probes. The patients had detectable (30% of normal) factor IX antigen. DNA hybridization analysis demonstrated that these patients had a partial intragenic deletion in their factor IX gene. This 2.8-kb deletion included exon d and the surrounding sequences. This exon codes for the amino acid sequence from No. 47 through 84 of the factor IX protein and contains its first potential EGF domain; the de novo occurrence of the mutation in the grandfather's germ cells was established by linkage analysis. This specific gene has been named F IXStrasbourg. PMID- 2875755 TI - The spectrum of beta-thalassemia genes in China and Southeast Asia. AB - To make possible prenatal diagnosis of beta-thalassemia in China and Southeast Asia by direct detection of mutant beta-globin genes, we have determined the spectrum of mutations producing the disorder in this region of the world. Seventy eight beta-thalassemia genes from Chinese and Southeast Asians were randomly obtained, and the relevant mutation was characterized in 76 (98%) of them. Seven different point mutations were found among the 78 genes studied. Of these seven beta-thalassemia alleles, two constitute 62%, and two others account for 29% of the total. Since only four alleles make up 91% of the mutant genes, prenatal diagnosis of beta-thalassemia in China and Southeast Asia should be feasible by simplified techniques for direct detection of point mutations. PMID- 2875756 TI - The 18- to 23-kb deletion of the Macedonian delta beta-thalassemia includes the entire delta and beta globin genes. AB - Restriction endonuclease mapping analyses were made of DNA from a few members of a Macedonian family with hematological characteristics of delta beta-thalassemia, ie, microcytosis, normal HbA2 levels, and elevated levels of HbF (7% to 14%) with G gamma (average 40.5%) and A gamma T chains (average 59.5%). A large deletion of 18 to 23 kb was present with a 5' breakpoint within a 670-bp segment of DNA between the HpaI and NcoI restriction sites 5' to the delta globin gene, and a 3' breakpoint between the BamHI and HpaI restriction sites located some 9 to 13 kb 3' to the beta globin gene. This deletion is different from those present in other types of G gamma A gamma(delta beta)zero-thalassemia. The similarity of the hematological expression of these delta beta-thalassemic conditions which have somewhat comparable 5' breakpoints supports the idea that an important fetal hemoglobin-controlling region lies between the psi beta and delta globin genes. PMID- 2875757 TI - Low dose maintenance medication for schizophrenia. PMID- 2875758 TI - AIDS, cotton wool spots, and cytomegalovirus retinitis. PMID- 2875759 TI - Influence of intrinsic sympathomimetic activity on respiratory function during chronic beta blockade. PMID- 2875760 TI - Increased secretion of somatostatin-28 from hypothalamic neurons of aged rats in vitro. AB - The purpose of this experiment was to determine whether increased secretion of somatostatin or alterations in its molecular form contribute to the age-related decline in growth hormone secretion. Median eminences were removed from male Sprague-Dawley rats (3-4 and 21-24 months of age) and superfused with Krebs Ringer bicarbonate buffer with 0.5 mg/ml bacitracin. After 40 min, tissues were stimulated with 55 mM K+ for 5 min and fractions collected for 60 min. Tissue and superfusate were analyzed for somatostatin using a highly specific antiserum which cross-reacts with somatostatin-14 and -28. Somatostatin release was expressed as a fractional efflux of somatostatin tissue content. In young rats, somatostatin increased from basal levels of 22 +/- 5 X 10(-4) to 57 +/- 3 X 10( 4) in response to 55 mM K+ and returned to basal levels. Old rats exhibited similar basal levels of somatostatin efflux (25 +/- 5 X 10(-4)) but increased to 91 +/- 19 X 10(-4) in response to K+. This represents an 89% greater increase in somatostatin fractional efflux in old as compared to young rats (P less than 0.05). The molecular form of somatostatin released during K+ stimulation was determined by fractionating samples on Sephadex G-25. In young animals, both somatostatin-14 (31% of total immunoreactivity) and somatostatin-28 (69% of total immunoreactivity) were released by hypothalamic neurons. In old rats, similar absolute levels of somatostatin were released in response to K+ but greater quantities of somatostatin-28 (87% of total immunoreactivity) were secreted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875761 TI - Dopamine modulates evoked transmission at cholinergic synapses formed by rat retinal neurons with muscle cells. AB - The purpose of this study was to investigate the effect of dopamine on synaptic transmission mediated by cholinergic neurons derived from the rat retina. We used a cell culture system that permitted the physiological monitoring of acetylcholine released at synapses formed between retinal neurons and striated muscle cells. Dopamine was found to facilitate evoked transmission by a mechanism mediated by D1 dopamine receptors. The results support the hypothesis that dopamine may have a modulatory role in information processing by the mammalian retina. PMID- 2875762 TI - Age-related increase in presynaptic noradrenergic markers of the rat cerebral cortex. AB - Age-related alterations in the noradrenergic innervation of the cerebral cortex were investigated in young (3-4 months) and aged (28-29 months) Fischer-344 rats. The concentration of noradrenaline and the activity of tyrosine hydroxylase, the probable rate-limiting step in catecholamine biosynthesis, were significantly higher in the aged cerebral cortex, but no differences in L-3,4 dihydroxyphenylalanine decarboxylase activity were observed. The specific high affinity uptake of noradrenaline by homogenates of the aged cerebral cortex exhibited higher maximal uptake, but lower affinity, than those of young rats. These results suggest increased presynaptic noradrenergic activity in the cerebral cortex of aged Fischer-344 rats. PMID- 2875763 TI - Exposure of hippocampal slices to quisqualate sensitizes synaptic responses to phosphonate-containing analogues of glutamate. AB - Exposure of transverse slices of rat hippocampus to quisqualate (Quis) resulted in a marked increase in the potency of D- and L-2-amino-4-phosphonobutanoate (APB) and D- and L-2-amino-5-phosphonopentanoate (APV) for depression of extracellular synaptic field potentials recorded from CA1 pyramidal cells. L-APB depressed the amplitude of CA1 field potentials with an IC50 = 1800 microM before exposure to Quis. After a brief (4 min) exposure to sufficient Quis (16 microM) to depress the response by 50%, L-APB depressed these responses with an IC50 = 54 microM. These phosphonate-containing glutamate analogues transiently induced population-spiking after the tissue was pretreated with Quis. This suggests that APB and APV can act as agonists at micromolar concentrations. PMID- 2875764 TI - The relative potencies of (-)-2-amino-5-phosphonovalerate and (-)-2-amino-7 phosphonoheptanoate as antagonists of N-methylaspartate and quinolinic acids and repetitive spikes in rat hippocampal slices. AB - The active (-)-isomers of 2-amino-7-phosphonoheptanoic acid (2-APH) and 2-amino-5 phosphonopentanoic acid (2-APV) have been compared as antagonists of N-methyl-D,L aspartate (NMDLA) and quinolinic acid on rat hippocampal slices. 2-APH appeared to be about 3 times more potent than 2-APV, though the same ratio was obtained against NMDLA and quinolinic acid. It is suggested that this difference of potency may partly explain the greater anticonvulsant activity of 2-APH. The results are consistent with the view that quinolinate acts at the NMDLA receptor while a differentiation between NMDLA and quinolinic acid is not likely to contribute to the anticonvulsant activities of 2-APH and 2-APV. A 3-fold difference of potency is also shown for (-)-2-APH and (-)-2-APV when blocking bicuculline-induced repetitive spikes in the CA1 region. This would support the involvement of an NMDLA receptor in this phenomenon. PMID- 2875765 TI - The role of the mediobasal arcuate hypothalamus in relation to opioid systems in the control of ingestive behaviour in the rat. AB - Bilateral, radiofrequency lesions of the mediobasal arcuate hypothalamus (MBH) strongly depleted levels of immunoreactive (ir)-beta-endorphin (beta-EP) in the hypothalamus and other brain tissues: these changes reflect destruction of those beta-EP-containing perikarya which are located in the MBH. No change in plasma ir beta-EP was seen. The ir-dynorphin (DYN) content of the hypothalamus was also depressed while that of ir-Met-enkephalin was unaffected. The fall in hypothalamic ir-beta-EP was correlated with the fall in that of ir-DYN. Lesioned rats displayed only a minor, transient reduction in rate of weight gain between days 3 and 9 postsurgery: this disappeared thereafter. Further, the lesion did not affect the pattern of weight loss and regain associated with 24 h food and water deprivation. Indeed, the total 24 h (daily) food intake (FI) and water intake (WI) of lesioned rats did not differ from that of sham animals while deprivation-induced hyperphagia and hyperdipsia was not attenuated by the lesions. Moreover, the ability of naltrexone to decrease FI and WI (during both dark and light phases of the daily cycle) was not altered by the lesions. These observations indicate that central beta-EP may not be essential for the maintenance of a normal 24 h FI and WI and that opioid antagonists do not act upon the MBH or upon central beta-EP neurones in their suppression of FI and WI. Further, they suggest that central beta-EP may not fulfil an essential role in the control of body weight in the rat. Lesioned rats did, however, reveal a shift in the diurnal rhythmicity of FI and WI reflected in a reduction in the dark:light ratios of these. An alteration in the diurnal rhythmicity of sleeping and core temperature, but not locomotor activity, was also seen. The shifts in hypothalamic ir-beta-EP and ir-DYN (but no other tissue levels of any peptide) were correlated with the magnitude of the shifts in diurnal rhythmicity of ingestive behaviour. Moreover, lesions caudal to the MBH (not affecting hypothalamic ir-beta-EP or ir-DYN) or dexamethasone treatment (which affects pituitary pools of ir-beta-EP and ir-DYN) did not modify these rhythms. Thus, in these respects, the effects are 'particular' to MBH lesions modifying hypothalamic ir-beta-EP and ir-DYN. The data suggest that the MBH may play a role in the modulation of the diurnal scheduling of ingestive behaviour in the rat.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2875766 TI - Coexistence of enkephalin and dynorphin immunoreactivities in neurons in the dorsal gray commissure of the sixth lumbar and first sacral spinal cord segments in rat. AB - The dorsal gray commissure (DGC) of the sixth lumbar (L6) and first sacral (S1) spinal cord segments in the rat has been shown to contain several different peptides, including enkephalin (ENK) and dynorphin (DYN). The present study was conducted to determine if DYN and ENK immunoreactivities coexist in neurons in the DGC in L6 and S1. Coexistence was determined using the elution/restaining technique of Tramu in which sections were stained first with anti-DYN then with anti-ENK after elution of the DYN antiserum. The number and location of DYN immunoreactive cells was compared to the number and location of ENK immunoreactive cells using photographic negatives. Of 67 ENK-immunoreactive cells counted in 20 sections through L6, 54 also contained DYN immunoreactivity. Of 100 ENK-immunoreactive cells counted in 47 sections through S1, 95 also contained DYN immunoreactivity. No cells with only DYN immunoreactivity were seen. S1 was found to contain a significantly greater number (P less than 0.005) of ENK immunoreactive cells that also contained DYN than L6. The results of these studies indicate that ENK and DYN immunoreactivities coexist in most, but not all, neurons in the DGC of L6 and S1 and that a difference exists between L6 and S1 in the extent of coexistence of these peptides. Further studies are necessary to determine if coexistence of opioids is limited only to autonomic regions of the nervous system and also to define the functional significance of this coexistence. PMID- 2875768 TI - A new method for producing a specific and high titre antibody against glutamate using colloidal gold as a carrier. AB - Antiserum against the glutamate was developed using colloidal gold as a carrier for the antigen. Glutamate was bound directly to colloidal gold without using cross-linking reagents such as glutaraldehyde, formaldehyde, or carbodiimide. Repeated injection of the colloidal gold-glutamate complex into the rabbit yielded a specific, high titre antiserum. Specificity was verified by radioimmunoassay and histochemically with absorption controls. The antiserum immunohistochemically detected numerous glutamate-containing neurons in the rat brain. PMID- 2875767 TI - Cardiorespiratory effects produced by microinjecting L-glutamic acid into medullary nuclei associated with the ventral surface of the feline medulla. AB - The purpose of our study was to use microinjections of L-glutamic acid to better localize the cell bodies in the intermediate area of the ventral medullary surface that exert control over cardiorespiratory activity. L-glutamic acid (200 nl of a 1-M solution) was microinjected into the nucleus paragigantocellularis lateralis, lateral reticular nucleus and into an area which is part of the 'glycine-sensitive area', which lies in the center of the intermediate area. Normally, when L-glutamic acid is applied to the surface of the intermediate area, increases in arterial pressure and tidal volume are observed. Increases in tidal volume were never observed upon microinjection into the 3 sites associated with the intermediate area, suggesting that the tidal volume change elicited from surface application occurs because of L-glutamic acid interacting with cell bodies either on the surface or extremely close to the surface. Pressor responses were elicited with microinjection of L-glutamic acid into the lateral reticular nucleus and the 'glycine-sensitive area', but not the nucleus paragigantocellularis lateralis; indeed, microinjection of L-glutamic acid into the nucleus paragigantocellularis lateralis caused hypotension. Hence, cell bodies responsible for raising arterial pressure may reside in either the lateral reticular nucleus or the 'glycine-sensitive area'. PMID- 2875769 TI - Excitatory amino acid antagonists depress transmission in hippocampal projections to the lateral septum. AB - Antagonists of excitatory amino acid neurotransmission were tested as antagonists of septal excitatory postsynaptic potentials (EPSPs) generated by stimulation of the fimbria. Septal EPSPs were depressed in a concentration-dependent manner by kynurenic acid and P-bromobenzoyl piperazine-2,3-dicarboxylic acid but not by L-2 amino-4-phosphonobutyric acid or D-2-amino-5-phosphonopentanoic acid. These results indicate that the hippocampal projection to the lateral septum is similar to the Schaffer collateral system and is mediated by an excitatory amino acid or a similar derivative. PMID- 2875770 TI - The neurobiologic consequences of Down syndrome. AB - Trisomy of the whole or distal part of human chromosome 21 (HSA 21) (Ts21) results in Down Syndrome (DS), which is characterized in part by mental retardation and associated neurological abnormalities. Structural abnormalities observed frequently include reduced brain weight, decreased number and depth of sulci in the cerebral cortices, neuronal heterotopias, and reduced numbers of specific populations of neurons, such as granule cells, in the cerebral cortices. Abnormalities in the structure of cells, primarily of the dendrites, are observed in portions of the neuraxis, such as the hippocampus, cerebellum, and cerebral cortices. Functional abnormalities in membrane properties in peripheral structures and in neurotransmitter enzyme systems in both peripheral and central structures are observed also. Brains of DS individuals over the age of 40 exhibit the characteristic neuropathologic and neurochemical stigmata of Alzheimer's disease (AD). The cholinergic and noradrenergic systems appear to be particularly vulnerable. To elucidate the mechanisms responsible for these abnormalities, identification of the genes located in the distal part of HSA 21 and the systematic study of animal model systems with close genetic homology are essential. PMID- 2875771 TI - Mouse chimeras composed of trisomy 16 and normal (2N) cells: preliminary studies. AB - Many humans with trisomy 21 (Down Syndrome (DS)) have psychomotor and cognitive retardation, congenital heart disease, and hematologic abnormalities. Partial genetic homology exists between mouse chromosome 16 and human chromosome 21; thus, studies of the development of mice with trisomy 16 (Ts16) may provide important insights into the pathogenesis of these defects and into the mechanisms by which they arise in humans. Since Ts16 mice do not survive the late fetal period, chimeras have been formed between Ts16 and normal (2N) mouse embryos to rescue the Ts16 cells for postnatal studies. In this preliminary study of the postnatal development of such chimeras, we examined the proportion of Ts16 cells in a variety of tissues, including the coat, blood, placenta, heart, and brain. The Ts16 cells made significant contributions to almost all tissues examined. Aspects of the behavior and the neurochemistry of adult Ts16 less than-greater than 2N chimeras were found to differ significantly from control (2N less than greater than 2N) chimeras and from animals of the two donor embryo strains. Ts16 cells comprised a substantial, but not predominant, proportion of cells in each brain region examined. Suggestions for definitive analyses are reviewed. PMID- 2875772 TI - Thy-1-like immunoreactivity in human brain during development. AB - Thy-1-like immunoreactivity was found in several areas of the immature and adult human brain, using indirect immunofluorescence techniques. In the fetal brain (31 gestational weeks) most immunoreactivity was located in the white matter with an overall granular diffuse distribution and stray fluorescent fibrous structures radiating into grey matter. At 2 months postnatally, the large axon bundles of the internal capsule traversing the caudate nucleus were strongly positive, whereas surrounding neuropil seemed to be negative. In the adult caudate nucleus no such fluorescent fibre bundles could be observed. At 8 months of age, both cerebellum and frontal cerebral cortex contained large numbers of fibrous structures in the grey matter in addition to white matter fluorescence. The molecular layer of both areas was negative. The 8-month-old cerebellum had a Thy 1 distribution similar to the adult, while in the frontal cortex cerebri the density of fluorescent structures increased gradually until adulthood. However, in the 5-year-old frontal cortex the immature granular appearance of 2-month-old cortex could still be seen, but with a greater number of radiating fluorescent bundles. In the adult brain, cerebellum contained a dense pattern of thick, fibrous fluorescent structures in white matter and the internal granular layer and in the frontal cortex thick bundles radiated into grey matter to form a plexus of coarse individual fibres in layers II and III. The hippocampal formation of the 31-week-old fetus contained a network of thin varicose fibres, ascending from the white matter. Stratum radiatum at this stage contained numerous small spots of Thy-1-like immunoreactivity, but no visible fluorescent fibres.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875773 TI - [Curarization accelerated by priming]. PMID- 2875774 TI - Rational management following diagnosis of myocardial ischemia. AB - Assuming one knows that myocardial ischemia is present, rational management will first require a careful history to assess the severity of symptoms, such as angina, the lifestyle of the patient, his/her age, and the availability of resources. When a patient is greater than or equal to 70 years, has little angina, even the demonstration of ischemia will not require early arteriography; pharmacological therapy on a trial basis is the preferred approach. Judging the response to oral nitroglycerine, isosorbide dinitrate, beta blockers and calcium antagonists, (often combined and in modest doses) is good rational management. If symptoms persist despite therapy or when the patient is younger and has symptoms which cannot be alleviated by changes in lifestyle and/or workload, the established ischemia assumes much greater significance and nearly always requires a coronary arteriogram for proper management. Once the coronary arteriogram has been analyzed in terms of severity of flow impairment, correlation with the tests showing the extent of myocardial ischemia must be made, best during exercise. If single vessel disease is found with a local dyskinetic (echo, scintigraphy, or angio) segment, which corresponds to a stenosis of greater than or equal to 70%, particularly when found in the anterior descending artery, balloon dilatation (PTCA) or bypass surgery (CABG) should follow. When tests, such as the ECG, are obtained during an attack of angina, the Chahine classification may be used first. In Class IIa with pure ST-segment elevation significant atherosclerotic lesions are absent in most patients, while local spasm can be shown upon provocation. Here rational management can be limited to calcium antagonists sometimes combined with beta blockers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875775 TI - Forskolin: effects on cyclic AMP and contractile function in the isolated rat and guinea pig heart. AB - The new inotropic agent, forskolin, is thought to act by stimulation of adenyl cyclase at a site remote from the beta-receptor. In this study we have characterized the action of forskolin in isolated, perfused rat and guinea-pig hearts. In both species, forskolin increased heart rate, left ventricular pressure and tissue cyclic AMP in a concentration-dependent manner. Significant responses were obtained with a minimum concentration of 2 X 10(-9)M forskolin in the rat and 2 X 10(-8)M in the guinea-pig. In both species maximal effects were observed with 2 X 10(-6)M forskolin. For any given forskolin concentration, the increases in cyclic AMP were greater in the rat heart than in the guinea-pig heart. In the rat heart, two beta-adrenoceptor blocking agents (1.6 X 10(-6)M propranolol or 2.6 X 10(-6)M timolol) were both able to reduce the increases in function and tissue cyclic AMP content caused by forskolin (2 X 10(-7) and 2 X 10(-8)M). However, no inhibition by beta-blockade was observed in hearts from catecholamine-depleted (reserpinized) animals or in hearts treated with high concentrations (2 X 10(-6)M) of forskolin. These results indicate that catecholamines may in some way be able to potentiate the actions of forskolin. PMID- 2875776 TI - Ocular distribution of methyprylon after intravenous injection and transfer of the drug to recipient eye via corneal graft. AB - The purpose of the study was to determine chronologically the ocular distribution of methyprylon (Noludar) after a single intravenous injection (45 mg/kg) to rabbits, if the drug can be transferred from a donor treated with the drug to the recipient's eye via an allogeneic corneal graft, and the effect of methyprylon on corneal cell growth and protein synthesis. Gas chromatographic techniques showed that the drug was present in all the tissues and fluids of the eye from 0.5 to 18 hours after the injection. Postoperatively, the cornea and some of the other ocular tissues of the recipient contained methyprylon at least 24 hours after transplantation. Clinically, the graft remained clear, and there was no adverse reaction in the recipient eye for an observation period of 24 hours. Tissue culture studies showed that about 10 times more methyprylon than was found in the donor cornea was necessary to produce a cytotoxic reaction on the corneal cells in terms of cellular growth rate and protein synthesis. Our animal experiments and cytotoxicity tests suggest that corneas of donors treated with a high dose of methyprylon would be suitable for use as grafts. PMID- 2875777 TI - Synthesis and biological activity of analogs of dynorphin-A(1-13) substituted in positions 2 and 4: design of [Ala2,Trp4]-Dyn-A(1-13) as a putative selective opioid antagonist. AB - Mono- and di-substituted analogs of dynorphin-A(1-13) (Dyn-A(1-13)) were synthesized by the solid-phase procedure. The products were purified and analyzed for their ability to inhibit the electrically evoked contractions of the guinea pig ileum (GPI) and mouse vas deferens (MVD) and to compete with the binding of [3H]etorphine ([3H]ET) and [3H]ethylketocyclazocine ([3H]EKC) to homogenates of rat brain (mu-, delta-, kappa 2-receptors) and guinea pig cerebellum (kappa receptor), respectively. Introduction of Ala in position 2 caused a drastic decrease in the activity of the peptide on the smooth muscle preparations (IC50 of 104 and 2.250 nM in the GPI and the MVD as compared with 0.7 and 21 nM for the parent peptide, respectively). Conversely, this analog retained much of the opioid binding activity of Dyn-A(1-13) (relative binding potencies of 15 and 72% for the displacement of [3H]ET and [3H]EKC, respectively). The replacement of Phe4 by Trp also caused drastic decreases in the activity of the peptide in the smooth muscle preparations (relative potencies of 0.8 and 8.8% on the GPI and MVD) while much of the binding potency to the opioid receptors was retained (31 and 67% for the displacement of [3H]ET and [3H]EKC, respectively). [Ala2,Trp4] Dyn-A(1-13) was the least potent peptide tested in the smooth muscle assays (relative potencies: 0.1 and 0.6%). However, this latter analog still retained some opioid binding activity in the displacement of [3H]ET to rat brain homogenates (3%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875778 TI - Adrenoceptor function in the bovine pulmonary circulation. AB - The bovine pulmonary vascular response to alpha- and beta-agonists was studied using an awake intact calf model. Pulmonary arterial pressure, pulmonary arterial wedge pressure, left atrial pressure, systemic arterial pressure, and cardiac output were measured in response to 3 min infusions of isoproterenol (beta agonist; 0.12, 0.24, 0.48, 0.9, and 1.8 micrograms X kg-1 X min-1) and phenylephrine (alpha-agonist, 0.15, 0.30, 0.60, 1.15, and 2.30 micrograms X kg-1 X min-1). Phenylephrine caused an increase in vascular resistance in the pulmonary arterial and venous compartments. The slope of the resistance in response to phenylephrine was greater in the pulmonary arterial than pulmonary venous circulation. Isoproterenol resulted in a dose-dependent decrease in vascular resistance in the pulmonary arteries and veins. The vascular resistance was decreased to the same level in the pulmonary arteries and veins although the arteries showed a greater percent change. In addition, isoproterenol infusion resulted in a transient decrease in arterial pH and increase in values for packed cell volume and haemoglobin. PMID- 2875779 TI - 14-beta-Methyl-8-oxacyclorphan (BC-3016), a morphinan derivative with high affinity for kappa opioid receptor: comparison with dynorphin-A(1-13). AB - 14-beta-Methyl-8-oxacyclorphan (BC-3016) was tested for its ability to depress the electrically evoked contractions of the guinea pig ileum (GPI) and of the mouse vas deferens (MVD) and to compete with the binding of prototype ligands selective for kappa-, mu-, or delta-opioid receptors in membrane preparations of rat brain and guinea pig cerebellum. BC-3016 was a very potent agonist in the GPI and MVD preparations, with ID50 of 0.7 and 31 nM, respectively. The activity of levorphanol, a standard alkaloid related to BC-3016, was much lower in both assays with ID50 values of 44 and 86 nM, respectively. Conversely, the activity of BC-3016 was quite comparable to that of dynorphin-A(1-13) in both preparations. In the GPI assay, a putative kappa-receptor antagonist, MR-2266, was 6.6 and 5.5 times more potent than naloxone in blocking the activity of BC 3016 and dynorphin-A(1-13), respectively. BC-3016 was also very potent in displacing bound [3H]ethylketocyclazocine ([3H]EKC) to membrane preparations of the guinea pig cerebellum, a brain component containing predominantly kappa opioid receptors (Ki of 0.58 nM). Its potency in the displacement of the bound mu ligand, 3H-labelled (D-Ala2,MePhe4,Gly-OH5)-enkephalin ([3H]DAGO), to rat brain homogenates was somewhat lower (Ki of 0.8 nM) but still high when compared with its ability to displace the delta-ligand, 3H-labelled (D-Ser2, Thr6)-Leu enkephalin ([3H]DSLET) to rat brain homogenates (Ki of 4.45 nM). The affinity of BC-3016 for the opioid receptor was 2.1-fold higher than that of U-50488H, a selective kappa-opioid ligand.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875780 TI - Proteins and amino acids: effects on the sympathetic nervous system and blood pressure regulation. AB - Many functions of the brain and the sympathetic adrenal system are influenced by those amino acids that exert precursor control over neurotransmitter synthesis. One of the functions affected is regulation of blood pressure. Therefore, the purpose of this review is to describe how food proteins and amino acids affect the synthesis of neurotransmitters and their regulation of blood pressure. PMID- 2875781 TI - Prevalence of psychoactive medication in children and adolescents. AB - Prevalence studies in Psychopharmacology are few and have many methodological flaws. This study examines the prevalence of psychoactive drugs in children and adolescents. Contrary to other studies, central nervous system stimulants are not the most widely prescribed psychoactive drugs in childhood and adolescence, but rather, minor tranquilizers, sedatives and hypnotics are the most widely prescribed psychoactive drugs. While this study overcomes some of the flaws of previous studies further studies regarding the prevalence of use of psychoactive drugs in childhood and adolescence are recommended. PMID- 2875782 TI - Negative symptoms and neuroleptic response. PMID- 2875783 TI - Significance of chromosome 14 anomaly at band 14q11 in Japanese patients with adult T-cell leukemia. AB - The chromosomes of leukemic blood cells in eight Japanese patients with acute adult T-cell leukemia (ATL) were examined by a direct method or short-term culture method without any mitogens. Six patients showed a chromosome 14 anomaly with a break at band q11-13: inv(14)(q11q32) in two patients, t(11;14)(p13;q13) in one patient, t(14;14)(q11;q32) in addition to del(14)(q11q13) in another, and only del(14)(q11q13) in two patients. Thus, a proximal 14q rearrangement exists in ATL as in other types of T-cell malignancies. Based on these facts, the pathogenesis of ATL is discussed in reference to the literature. PMID- 2875784 TI - Paraganglioma of the cauda equina region. Clinicopathologic study of 31 cases with special reference to immunocytology and ultrastructure. AB - Thirty-one paragangliomas of the cauda equina region were studied (18 men and 13 women, ages 30-71 years [mean, 51 years]). Symptoms (1 day to 15 years in duration; mean, 48 months) included low back pain (87%), sensory/motor deficits (35%), urinary/fecal incontinence (13%), and paraplegia (6%). All patients studied had some myelographic block. Cerebrospinal fluid protein level ranged from 56 to 7000 mg/dl (mean, 1109 mg/dl). Most tumors were limited to the filum terminale, although one also involved the conus medullaris and two clearly arose from a caudal nerve root. All but one were entirely intradural. The tumor was totally excised in 26 cases; these patients remain disease-free. Of three patients whose tumors were excised subtotally, two received radiotherapy; the one non-radiated patient died of tumor-related complications. No autopsy was performed. One partially encapsulated tumor that had been subjected to biopsy and irradiation presented 1 year later with osseous invasion and retroperitoneal extension; 20 years after subtotal excision, this patient is alive but paraplegic. Morphologically, all tumors resembled paraganglioma at other sites. Cytologic atypia and mitotic activity generally were absent to mild. Fourteen (45%) cases showed ganglionic differentiation. All tumors tested were immunoreactive for neuron-specific enolase and neurofilament protein, and most showed somatostatin or serotonin reactivity. S-100 protein immunoreactivity was noted in sustentacular cells and, to a lesser extent, within chief cells and neurons. The authors conclude that paragangliomas are largely benign and encapsulated and respond to simple resection. When surgically feasible, gross total removal should be the goal of surgery. When subtotal resection is necessary or when local invasion leaves a question as to completeness of tumor removal, irradiation seems mandatory although far from guaranteeing prevention of recurrence. Biopsy alone is undesirable. PMID- 2875785 TI - Malignant melanoma in multiple endocrine neoplasia. AB - Because of its neurocrest APUD origin, malignant melanoma has been postulated to be a component of the multiple endocrine neoplasia (MEN) syndromes; however, such a case has not been previously described. Prior associations of melanocytes with the MEN syndromes have been confined to hyperplasia. This report describes the first case of malignant melanoma occurring in a patient with the MEN IIA syndrome (bilateral pheochromocytomas and medullary thyroid carcinoma). The role of melanocytic hyperplasia and neoplasia within the MEN syndromes is discussed. PMID- 2875786 TI - Incidence and descriptive features of testicular cancer among United States whites, blacks, and Hispanics, 1973-1982. AB - This is a descriptive epidemiologic report based on over 3000 incident testicular cancer cases occurring among residents of the US and Puerto Rico, as reported to the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute for the years 1973 through 1982. White men had significantly higher incidence rates than their New Mexico Hispanic, black, and Puerto Rican Hispanic counterparts with weighted risk ratios of 1.36, 4.62, and 4.80, respectively. Ethnic differences in incidence were least evident at the extremes of age. Although the distribution of histologic subtypes did not differ across ethnic strata, morphologic expression was related to age at diagnosis. There was a predominance of right-sided tumor involvement in each ethnic group in childhood (less than 15 years of age), but not in the oldest age categories or among tumors presenting in cryptorchid testes. Never married men appeared to be at greater risk of developing nonseminoma testicular cancer than their married counterparts. Analysis of ethnic secular trends, using data from comparable geographic areas, showed a consistent increase in incidence among young men for all three ethnic groups. The contrast between the rate differences and the homogeneity of descriptive parameters across ethnic strata suggest the impact of quantitative rather than qualitative differences in environmental etiology. PMID- 2875787 TI - Assessment of malaise in cancer patients treated with radiotherapy. PMID- 2875788 TI - Characterization of a new drug-resistant human myeloma cell line that expresses P glycoprotein. AB - Multiple myeloma is a disease with a high initial chemotherapeutic response but virtually no cures due to emergence of drug resistance. A doxorubicin-resistant human myeloma cell line (8226/Dox) has been selected from the myeloma cell line RPMI8226 by continuously exposing cells to gradually increasing doses of doxorubicin. The resistant phenotype has been retained for over 2 months despite growth in drug-free medium. The resistant subline was cross-resistant to mitoxantrone, acronycine, etoposide, and vincristine. The 8226/Dox cell line remained sensitive to melphalan but acquired collateral sensitivity to dexamethasone. Intracellular doxorubicin accumulation, as measured by [14C]doxorubicin and high-performance liquid chromatography, was decreased by 54% at 1 h for 8226/Dox compared to the sensitive line. Efflux of doxorubicin was significantly greater in the resistant subline as compared to the sensitive parent cell line. Membrane analysis using immunoblotting techniques detected increased expression of the integral membrane protein P-glycoprotein (Mr 170,000) in the resistant subline. Cytogenetic analysis of 8226/Dox revealed a 7q-anomaly not seen in the parent cell line. No double minutes or homogeneously staining regions were observed. The drug sensitivity/resistance pattern of the resistant cell line correlates well with clinical observations indicating the potential of this cell line as a model for resistance in multiple myeloma. PMID- 2875789 TI - Analysis of peroxisome proliferator-induced preneoplastic and neoplastic lesions of rat liver for placental form of glutathione S-transferase and gamma glutamyltranspeptidase. AB - Structurally unrelated peroxisome proliferators induce altered areas (AA), neoplastic nodules (NN), and hepatocellular carcinomas (HCC) in rats and mice. In this study we have examined several AA, NN, and HCC induced by Wy-14,643 and ciprofibrate in rats for gamma-glutamyltranspeptidase (GGT) and the placental form of glutathione S-transferase (GST-P) by histochemical and immunohistochemical procedures, respectively. In Wy-14,643-treated animals 96 100% of NN and HCC was negative for both GGT and GST-P. Eighty-seven % of the AA was negative for both GGT and GST-P, and only 2% was positive for both the marker enzymes. In ciprofibrate-treated animals 52% and 75% of AA were negative for GST P and GGT, respectively, and 16% was positive for both the enzymes. However, a large majority of NN and HCC (more than 95%) was devoid of both these marker enzymes. Thus these studies clearly indicate that the hepatic lesions induced by peroxisome proliferators display different phenotypic properties as compared to the lesions induced by commonly used classical liver carcinogens. We conclude that GGT and GST-P are not the ideal markers for identifying AA, NN and HCC induced by peroxisome proliferators. PMID- 2875790 TI - Enhanced expression of c-myc and decreased expression of c-fos protooncogenes in chemically and radiation-transformed C3H/10T1/2 Cl 8 mouse embryo cell lines. AB - c-abl, c-fos, c-Ha-ras, c-myc, and c-mos were expressed whereas c-sis, c-fms, c rel, c-src, and c-myb expression was not detectable in C3H/10T1/2 Cl 8 (10T1/2) cells and in eight chemically and radiation-transformed 10T1/2 cell lines. The expression of c-abl, c-fos, c-Ha-ras, and c-myc was growth-related in nontransformed 10T1/2 cells. c-abl and c-fos expression increased at confluence by 5- and 9-fold, respectively, compared to that in log phase cells. c-Ha-ras and c-myc transcripts were most abundant in log phase cells and decreased by 70 and 50%, respectively, in confluent cells. There were no significant growth-related changes in the expression of c-Ha-ras, c-myc, or c-abl in methylcholanthrene transformed Cl 15 cells. The c-fos transcript was not detected in Cl 15 cell cultures. c-abl, c-fos, c-ras, and c-myc were expressed in whole C3H mouse embryo tissue, mouse liver, and 10T1/2 cells. Sizes of these protooncogene transcripts in 10T1/2 cells were the same as those in whole embryo tissue, except that 10T1/2 cells did not express the 8.2-kilobase abl transcript. At subconfluence, equivalent low levels of c-mos expression were observed in nontransformed and in the eight transformed 10T1/2 cell lines. The level of c-abl expression was similar in the nontransformed and in the eight transformed cell lines, but there was a new 8.2-kilobase transcript in the transformed MCA Cl 15 cell line. c-fos was expressed in 10T1/2 cells but was not detectable or greatly reduced in eight transformed cell lines. c-Ha-ras was expressed to a similar extent in eight transformed cell lines and in nontransformed 10T1/2 cells. In the UVC-4 transformed cell line, extra 3.3-kilobase Ha-ras and 7.5-kilobase Ki-ras transcripts were observed. c-myc was expressed at 4- to 7-fold higher levels in six transformed cell lines compared to 10T1/2 cells. There were no major rearrangements in or amplification of the c-myc gene in three transformed cells overexpressing this gene 5-fold. These studies show that enhanced expression of c myc and decreased expression of c-fos correlate with the chemically and radiation transformed states of 10T1/2 cells. Changes in c-fos and c-myc oncogene expression may be casually linked to late stages of neoplastic transformation in these chemically and radiation transformed 10T1/2 cell lines. PMID- 2875792 TI - Choice of internal mammary artery or saphenous vein graft for myocardial revascularization. AB - The saphenous vein has been the traditional conduit for elective myocardial revascularization. Although readily available and adaptable to many configurations around the heart, it is prone to intimal hyperplasia and vein graft atherosclerosis, which diminish long-term patency and relief of symptoms. The internal mammary artery graft represents a marked improvement over the saphenous vein graft in many respects. Data are presented comparing saphenous vein graft patency with that of the internal mammary artery, bilateral internal mammary artery, free internal mammary artery, and sequential internal mammary artery grafts. PMID- 2875791 TI - Intrasplenic administration of interleukin-2 to potentiate specific chemoimmunotherapy in tumor-bearing mice. AB - Augmentation of specific chemoimmunotherapy by daily, intrasplenic injection of interleukin-2 (IL-2) was assessed in a methylcholanthrene (MCA)-induced fibrosarcoma model in C3H/HeJ mice. Daily access to the spleen was achieved by relocating the organ into the subcutis while leaving its blood supply intact. Following intrasplenic injection of 80 units of human IL-2 into MCA-F tumor bearing mice for 6 days, spleen cells tested in the local adoptive transfer assay showed specific neutralization of MCA-F, but not the antigenically different MCA D, tumor. Depletion of the spleen cell population with monoclonal antibodies and complement showed that the responding cell bore the surface markers Thy 1.2 and Lyt 2. Mice bearing established MCA-F tumors underwent a variety of chemoimmunotherapy regimens, including 1 microgram of 1-butanol, extracted isoelectrophoretically purified tumor-specific transplantation antigen, a single i.p. dose of cyclophosphamide (20 mg/kg), and/or either i.p. or intrasplenic injection of 80 units of IL-2. Specific triple chemoimmunotherapy including daily intrasplenic IL-2, but not i.p., administration was superior in the degree of tumor neutralization to all single or double therapy protocols. Furthermore, the combined triple modality inhibited spontaneous lung colonization by clone 9-4, a highly metastatic variant of MCA-F; both the numbers of lung colonies (median, 17; range, 2 to 55, versus median, 3, range, 0 to 42; P less than 0.005) and the incidence were decreased. The combined treatment group displayed 35% of hosts free of lung metastasis, while 100% of the control animals had lung colonies (P less than 0.02). Thus antitumor immunity was augmented in vivo using IL-2 delivered by intrasplenic, but not i.p., injection. Furthermore, chemoimmunotherapy including intrasplenic IL-2 injection potentiated the antitumor immunity achieved with combined tumor-specific transplantation antigen and cyclophosphamide. PMID- 2875793 TI - Beta blockers and calcium channel blocking agents in acute myocardial infarction. PMID- 2875794 TI - Short-time effects of taxol on the seminiferous epithelium of the rat. AB - The effect of taxol, an inhibitor of microtubule degradation, on the seminiferous epithelium was studied. Taxol arrested spermatogenesis at metaphase in both mitotic and meiotic germ cell division. Microtubules were seen to accumulate, especially in the cytoplasm of the spermatogonia, and also in the early spermatids and Sertoli cells. No microtubule accumulation was observed in germ cells during meiotic prophase. Formation of the flagellum was affected in developing spermatids. Peculiar lamellar structures, probably derived from degenerating mitochondria, were seen in the cytoplasm of late spermatids and Sertoli cells. The results are compared with the effects of other mitotic inhibitors such as colchicine and vinca alcaloids. PMID- 2875795 TI - Regeneration of Leydig cells in unilaterally cryptorchid rats: evidence for stimulation by local testicular factors. AB - Leydig cells in testes of adult rats were selectively destroyed by a single intraperitoneal injection of ethane dimethane sulphonate. Four days later rats were made unilaterally cryptorchid and 1, 2 and 4 weeks later the histology of the testes were examined by light microscopy and morphometry. After induction of unilateral cryptorchidism, the volume of abdominal compared to scrotal testes was reduced by 45-60% due to rapid impairment of spermatogenesis in abdominal testes. Leydig cells were not present in either scrotal or abdominal testes in the 1-week unilateral cryptorchid group. A new generation of foetal-type Leydig cells were observed in scrotal testes of the 2-week unilateral cryptorchid group although their total volume per testis estimated by morphometry, was small, being approximately 1 microliter. In contrast, the abdominal testis exhibited a remarkable proliferation of foetal-type Leydig cells (total volume per testis, 16 microliter) which predominantly surrounded the peritubular tissues of the seminiferous tubules. A similar morphology and pattern of Leydig cell development was observed in scrotal and abdominal testes of the 4-week unilateral cryptorchid group where total Leydig cell volume was 7 microliter vs 21 microliter, respectively. The results show that regeneration of a new population of Leydig cells occurs more rapidly in the abdominal testis than in the scrotal testis of the same animal. These observations suggest the possibility that augmentation of Leydig cell growth is mediated by local intratesticular stimulatory factors within the abdominal testis. Development of new Leydig cells from the peritubular tissue provides circumstantial evidence that the seminiferous tubules and in particular the Sertoli cells, are a likely source of agents that stimulate the growth of Leydig cells. PMID- 2875796 TI - Ultrastructural localization of calcitonin and somatostatin in C cells of rabbit thyroid. AB - C cells of rabbit thyroid exhibit significant differences in morphology, namely a variable nuclear structure and differences in size and osmophility of secretory granules. An examination of serial sections of these cells was made, using the immunocytochemical PAP or protein A-gold procedures. All C cells, irrespective of their morphology, were found to store both calcitonin and somatostatin in all secretory granules. The physiological role of somatostatin in calcitonin secretion by C cells is discussed. PMID- 2875797 TI - A mitochondrial RNA maturase gene transferred to the yeast nucleus can control mitochondrial mRNA splicing. AB - bI4 maturase, encoded by the fourth intron of the yeast mitochondrial cytochrome b gene, controls the splicing of both the fourth intron of the cytochrome b gene and the fourth intron of the gene encoding subunit I of cytochrome oxidase. By fusing the encoding presequence of subunit 9 of the Neurospora ATPase to a restriction fragment containing the bI4 maturase coding sequence, we have constructed a hybrid gene that can be translated on yeast cytosolic ribosomes. The resulting protein is imported into mitochondria, which was revealed by its ability to restore to respiratory competence a yeast mutant defective in the bI4 maturase. Moreover, a protein reacting with antimaturase antibodies was detected in the mitochondria of the transformed cells; this imported maturase functioned similarly to the endogenous maturase. PMID- 2875798 TI - Developmental coordination of alpha-amylase and psp gene expression during mouse parotid gland differentiation is controlled posttranscriptionally. AB - We have compared the developmental expression of psp and Amy-1a genes during postnatal differentiation of the mouse parotid gland. The mRNAs encoded by both genes accumulate with identical kinetics and accumulate in the same subset of acinar cells early in development. Transcriptional activation of the two genes is unexpectedly asynchronous. While the increase of alpha-amylase mRNA levels in development arise from increased Amy-1a transcription, psp is transcribed at almost adult levels at 12 days of age, but cellular psp mRNA accumulation is very low. Since nuclear processing of psp pre-mRNAs and transport of mature mRNA into the cytoplasm occur with similar efficiencies in young and adult mice, the rapid turnover of psp mRNA in young animals occurs in the cytoplasm. PMID- 2875799 TI - Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl 2/immunoglobulin transcript resulting from the t(14;18) translocation. AB - cDNAs for the bcl-2 mRNA were cloned from a human common acute lymphoblastic leukemia cell line. Nucleotide sequence analyses showed that the 6 kb bcl-2 mRNA potentially encodes a 26 kd protein that is homologous to a predicted Epstein Barr virus protein. Most t(14;18) translocation breakpoints cluster within a narrow region of a 5.4 kb exon that contains a long 3'-untranslated region of the bcl-2 mRNA. As a result of t(14;18) translocation, hybrid bcl-2/immunoglobulin heavy chain transcripts are produced that consist of the 5' half of the bcl-2 mRNA fused to a "decapitated" immunoglobulin heavy chain mRNA. Nucleotide sequence analyses confirmed that the hybrid transcripts continue to encode a normal bcl-2 protein. Our results suggest that t(14;18) translocations alter expression of the bcl-2 gene both by transcriptional activation and by abnormal posttranscriptional regulation of bcl-2 mRNA. PMID- 2875800 TI - Analysis of T-T lymphocytes and T-accessory cell interactions using cloned T cells: MHC I restricted cloned T cells activate MHC II restricted T helper cells. AB - We evaluated the role of molecules of the major histocompatibility complex (MHC) involved in the cellular interactions of two T-cell clones by testing the effect of monoclonal antibodies on the responses of the clones in vitro. The two T-cell clones used in the study are specific for minor histocompatibility antigens and restricted to the H-2Kk. In the absence of exogenous IL-2 the clones require the presence of Ia+, Thy-1- accessory cells and of Thy-1+, Lyt-1+2- cells in the irradiated spleen cell suspension used as stimulator. It is also necessary that both the accessory cells and the T cells in the stimulator cell populations are recognized specifically by the clones. Monoclonal antibodies specific for the H 2K product inhibited the lytic effector function of the cytolytic clone. These antibodies when added to cultures of stimulator cells and clones inhibited also the proliferation of this clone and of a nonlytic clone. When antigen recognition was measured by the increase in sensitivity of the clones to IL-2 while confronted with uv-irradiated stimulator cells, both clones were blocked efficiently by anti-H-2K antibodies. Thus, these results suggest that the interaction of monoclonal antibodies with the restricting H-2K molecule is sufficient to block the recognition signal, a prerequisite for proliferation. In contrast, monoclonal antibodies specific for A alpha A beta and/or E alpha E beta had no effect on cytolysis or on restricted recognition. However, they inhibited the proliferative responses as efficiently as the H-2K specific antibodies. Inhibition by class II-specific antibodies was not abolished when stimulator cell populations were depleted of Lyt-2+ cells. The blocking effect, however, was reversed by the addition of IL-2. No inhibition was obtained with antibody specific for E alpha E beta when B10.A(4R) spleen cells, which do not express E alpha E beta, or when B10.A(4R) accessory cells, which were reconstituted with (BALB/c X B10.A(4R] F1 T cells, were used as stimulators. Stimulator cells heterozygous for H-2 could be inhibited by antibodies to the parental haplotype not encoded in the clones (H-2Kd). These and previous results suggest that H-2K restricted minor histocompatibility antigen-specific recognition transmits an activating signal to the clones and to the stimulator cells. The clones probably are induced to express more IL-2 receptors. The stimulator T cells seem to interact through A alpha A beta and E alpha E beta molecules with syngeneic accessory cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2875801 TI - Reduced prostaglandin E2 (PGE2) receptors on atopic T lymphocytes. AB - We have recently demonstrated that atopic T lymphocytes have decreased sensitivity to prostaglandin E2 (PGE2). In order to determine whether this decreased sensitivity was reflected at the receptor level, we have employed a radioligand binding assay utilizing [3H]PGE2. We have demonstrated a single specific reversible binding site for [3H]PGE2 on normal T cells (N = 10) with a mean KD (+/-SD) of 32.2 (+/-25.0) nM, a binding capacity of 20.2 (+/-13.0) pM, and a mean of 1004 (+/-118) receptors per cell. Atopic T cells (N = 10) were also found to have a single specific binding site for [3H]PGE2 with a mean KD of 24.9 (+/-17.8) nM, a binding capacity of 7.1 (+/-10.1) pM, and a mean of 372 (+/-61) receptors per cell. These radioligand binding studies were correlated with functional studies in the same subjects. Phytohemagglutinin-stimulated protein synthesis ([3H]leucine uptake) was suppressed in a dose-dependent fashion by PGE2 (10(-6)-10(-12) M). The maximal effect of PGE2 on normal T cells was 10(-6) M PGE2 with an IC50 of 10(-12) M. Atopic T cells responded quantitatively less than normal T cells to PGE2. Further, the maximum suppression of protein synthesis by PGE2 occurred at 10(-6) M with an IC50 of 10(-10) to 10(-11) M. These studies suggest that part of the decreased sensitivity of atopic T cells to PGE2 may result from a reduction in PGE2 binding sites. PMID- 2875802 TI - Independence of centriole formation and initiation of DNA synthesis in Chinese hamster ovary cells. AB - The relationship between centriole formation and DNA synthesis was investigated by examining the effect of taxol on the centriole cycle and the initiation of DNA synthesis in synchronized cells. The centriole cycle was monitored by electron microscopy of whole-mount preparations [Kuriyama and Borisy, J. Cell Biol., 1981, 91:814-821]. A short daughter centriole appeared in perpendicular orientation to each parent during late G1 or early S and elongated slowly during S to G2. Addition of 5-20 micrograms/ml taxol to a synchronous population of cells in S phase did not inhibit centriole elongation; rather, elongation was accelerated. In contrast, when taxol was added to M phase or early G1 cells, centriole duplication was completely inhibited. The taxol block was reversible since nucleation and elongation of centrioles resumed as soon as the drug was removed. Cells exposed to taxol progressed through the cell cycle and became blocked in mitosis, as indicated by an increase in the mitotic index, but eventually the mitotic arrest was overcome, resulting in formation of multinucleated cells. A peak in mitotic index was seen in the following generation, indicating that chromosomes duplicated in the presence of taxol. Incorporation of 3H-thymidine followed by autoradiography confirmed that DNA synthesis was initiated in the presence of taxol even though formation of daughter centrioles was inhibited. It seems, therefore, that centriole duplication is not a prerequisite for entry into S phase. Since DNA synthesis has already been demonstrated not to be necessary for centriole duplication, these two events, normally coordinated in time, appear to be independent of each other. PMID- 2875803 TI - [Species differences in the in vitro metabolism of oxyprothepine]. PMID- 2875804 TI - [The pharmacology of beta-blockers]. PMID- 2875805 TI - [The effect of various beta-blockers on the eye]. PMID- 2875806 TI - [First clinical impressions of metipranolol eyedrops in open-angle glaucoma]. PMID- 2875807 TI - [General contraindications of beta-blockers]. PMID- 2875809 TI - Facilitated expression of adaptive responses to phenobarbital in putative pre stages of liver cancer. AB - Female rats received N-nitrosomorpholine to produce altered cell foci (potential cancer pre-stages) in the liver, followed by phenobarbital (PB) for 2 weeks. As indicators of adaptive responses we measured DNA synthesis cumulatively by infusion of [3H]thymidine for the entire period of PB treatment, and cytochrome P450-PB by immunocytochemistry on histological liver sections. Altered cell foci were identified by expression of gamma-glutamyltransferase (gamma-GT), and/or altered morphology. The following results were obtained. In normal parts of the liver PB induced DNA replication only in association with expression of P450-PB; both responses were restricted to the pericentral area of the liver lobule. In foci, PB treatment led to enhanced DNA synthesis. Furthermore, PB caused a 3-fold increase in the number of foci expressing cytochrome P450-PB, gamma-GT or both. Cumulative determination of DNA synthesis showed that this increase did not result from selective proliferation of single initiated cells. It is concluded that in foci also PB can induce expression of the adaptive increases in cytochrome P450-PB and DNA synthesis. Foci show the responses to PB more readily than normal hepatocytes, and irrespective of their position within the liver lobule. These findings suggest that expression of adaptive responses to inducing tumor promoters is facilitated in altered foci. PMID- 2875810 TI - Enhancing effect of co-administration of polychlorinated biphenyls and diethylnitrosamine on enzyme-altered islands induced by diethylnitrosamine in rat liver. AB - The effect of co-administration of diethylnitrosamine (DEN) and Clophen A 50, a commercial mixture of polychlorinated biphenyls (PCB), on pre-neoplastic enzyme altered islands in livers of female Sprague-Dawley rats was studied. The islands were identified by the loss of adenosine-5'-triphosphatase (ATPase), emergence of gamma-glutamyltranspeptidase (GGTase) and glycogen storage after fasting. DEN was given p.o. (0.4 or 4 mg/kg body wt respectively) twice a week for 11 consecutive weeks. Clophen A 50 (1 or 5 mg/kg body wt respectively) was given alternatively three times a week for 11 weeks. Four groups of rats each received either DEN or PCBs in the respective doses. Control animals were treated with the vehicle or remained untreated. All animals were killed at week 12. In rats treated with 4 mg DEN/kg body wt approximately 80 ATPase-deficient islands/cm2 were observed. Additional treatment with Clophen A 50 enhanced the island number 3-fold. Treatment with 0.4 mg/kg body wt DEN induced 17 islands/cm2. Additional application of Clophen A 50 enhanced the island number approximately 3-fold. The total island area was enhanced to the same extent in both groups. The island incidence in PCB-treated rats and controls was below 1/cm2 with all markers tested. The results indicate that PCBs may exhibit a co-carcinogenic activity. PMID- 2875811 TI - Sequential study on the synergistic effects of 2,2',4,4',5,5'-hexabromobiphenyl and 3,3',4,4',5,5'-hexabromobiphenyl on hepatic tumor promotion. AB - A sequential study was completed to determine the effect of polybrominated biphenyl (PBB) congeners on the enhancement of gamma-glutamyl transpeptidase (GGT)-positive altered hepatic foci (AHF) and the development of hepatic nodules (HN) and carcinomas. Female Sprague-Dawley rats were given a single dose of N nitrosodiethylamine (NDEA) 24 h following a 70% partial hepatectomy. Thirty days later, rats were randomly assigned to groups and fed a basal diet or the basal diet containing 10 p.p.m. 2,2',4,4',5,5'-hexabromobiphenyl (245-HBB), 0.1 p.p.m. 3,3',4,4',5,5'-hexabromobiphenyl (345-HBB) or 10 p.p.m. 245-HBB plus 0.1 p.p.m. 345-HBB for 140 days followed by a basal diet for up to another 310 days. Rats from each group were killed 170, 240 or 480 days after partial hepatectomy. Dietary exposure to 245-HBB and 245-HBB plus 345-HBB enhanced the development of AHF and HN whereas 345-HBB alone did not. The combination of 245-HBB and 345-HBB caused a synergistic effect on the development of AHF and HN. The number of hepatocellular carcinomas was low and evenly distributed among the groups of rats fed diets containing PBB. PMID- 2875808 TI - Cumulative renal tubular damage associated with cisplatin nephrotoxicity. AB - We assessed the acute and chronic effect of multiple courses of cisplatin therapy on renal tubules by monitoring the urinary excretion of alanine aminopeptidase, N acetyl-beta-D-glucosaminidase, and total protein. Urine specimens were obtained before and after doses of cisplatin (90 mg/m2) given to 12 patients. Each dose of cisplatin induced transient increases in enzyme excretion, followed by proteinuria 3-5 days later. Transient enzymuria after the last cisplatin dose was significantly greater than that after the first dose. Moreover, persistent increases in urinary N-acetyl-beta-D-glucosaminidase and serum creatinine concentrations over pretherapy levels indicated chronic renal tubular damage. Our findings disclosed striking differences between patients in susceptibility to progressive nephrotoxicity. PMID- 2875812 TI - Effects of selective and nonselective beta-adrenergic blockade on mechanisms of exercise conditioning. AB - Exercise conditioning involves adaptations in the heart, peripheral circulation, and trained skeletal muscle that result in improved exercise capacity. Since the specific influence of beta-adrenergic stimulation on these various adaptations has not been clear, we studied the effect of beta 1-selective and nonselective beta-adrenergic blockade on the exercise conditioning response of 24 healthy, sedentary men after an intensive 6 week aerobic training program. Subjects randomly assigned to receive placebo, 50 mg bid atenolol, or 40 mg bid nadolol were tested before and after training both on and off drugs. Comparable reductions in maximal exercise heart rate occurred with atenolol and nadolol, indicating equivalent beta 1-adrenergic blockade. Vascular beta 2-adrenergic selectivity was maintained with atenolol as determined by calf plethysmography during intravenous infusion of epinephrine. All subjects trained at greater than 85% of maximal heart rate and 80% of VO2 max determined on drug. VO2 max increased after training 16 +/- 2% (p less than .05) in the placebo group and 6 +/- 2% (p less than .05) in the atenolol group, while there was no change in the nadolol group. At maximal exercise, subjects receiving placebo increased their exercise duration and oxygen pulse significantly greater than those receiving atenolol or nadolol. During submaximal exercise there were reductions in heart rate and heart rate-blood pressure product in all three groups, but these reductions were greater with placebo than with either drug. Leg blood flow during submaximal exercise decreased 24 +/- 2% (p less than .01) in the placebo group but was unchanged in the atenolol and nadolol groups. Lactates in arterialized blood during submaximal exercise were reduced equivalently in all three groups after training. Capillary/fiber ratio in vastus lateralis muscle biopsy specimens increased 31 +/- 6% in the placebo group and 21 +/- 6% in the atenolol group (both p less than .05) and tended to increase in the nadolol group. Succinic dehydrogenase and cytochrome oxidase activities in muscle biopsy specimens increased equivalently in all three groups, especially during submaximal exercise, these changes were less marked than that with placebo. While beta adrenergic blockade attenuated the exercise conditioning response, skeletal muscle adaptations including increases in oxidative enzymes, capillary supply, and decreases in exercise blood lactates were unaffected. Cardiac and peripheral vascular adaptations do appear to be affected by beta-adrenergic blockade during training. Cardioselectivity does not seem to be important in modifying these effects. PMID- 2875813 TI - Diagnostic significance of some urinary enzymes for detecting acute rejection crises in renal-transplant recipients: alanine aminopeptidase, alkaline phosphatase, gamma-glutamyltransferase, N-acetyl-beta-D-glucosaminidase, and lysozyme. AB - We compared the diagnostic validity of five urinary enzymes--alanine aminopeptidase (EC 3.4.11.2), alkaline phosphatase (EC 3.1.3.1), gamma glutamyltransferase (EC 2.3.2.2), N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30), and lysozyme (EC 3.2.1.17)--as indicators of acute rejection crises in renal transplant recipients. In 82 patients (group A), the excretion of each of these five enzymes was measured daily from transplantation until discharge from hospital. In another 69 patients (group B), enzyme determinations were made when the patient came for regular checkups (about every four to eight weeks). We used an "activity ratio" (the activity measured at a particular time compared with the activity on the preceding determination) value of 1.5 as the decision point. In group A, use of this discrimination point for alanine aminopeptidase, gamma glutamyltransferase, and N-acetyl-beta-D-glucosaminidase yielded a specificity and sensitivity of about 90%. In group B, only alanine aminopeptidase had a greater diagnostic sensitivity than creatinine alone. Evidently, measurement of alanine aminopeptidase can be a helpful indicator of acute rejection crises, when interpreted in combination with other available relevant clinical, biochemical, and immunological data. PMID- 2875814 TI - Serum concentration of human growth hormone (hGH) after administration of the somatostatin analogue SMS 201-995 in normal subjects. PMID- 2875815 TI - Long term therapy by captopril in children with renal hypertension. AB - We report on 29 treatment courses in 25 children aged 1.5-18 years who received captopril because of severe renal hypertension. The mean initial dosage was 1.3 (0.5 to 3) mg/kg/day and the mean sustaining dose 2.2 mg/kg/day. The treatment was followed for 2-40 (mean 15) months. We observed a lowering of both systolic and diastolic blood pressure (BP) from 26% at the 2nd day to 65% at the 6th month. The isolated use of captopril was ineffective in 13% of cases, but blood pressure dropped in all of them after addition of beta blocking agents. No clear cut relation was found between response of blood pressure and etiology, degree of HT or plasma renin activity (PRA). No side effects occurred during treatment except for one case of reversible acute renal failure in a transplanted patient with renal artery stenosis. PMID- 2875817 TI - Paternal non-disjunction in a 46,XY/47,XXY individual with a fragile 17p12 in the mother. AB - In a family where the mother carried a fragile site at 17p12, RFLP-analysis with the X-specific probe L1.28 showed that the 46,XY/47,XXY mosaicism detected in her Klinefelter son was due to a non-disjunctional event in paternal meiosis I, followed by a secondary loss of an X-chromosome by a mitotic non-disjunction. Thus, an association between the primary meiotic non-disjunction and the presence of the fragile site could be excluded. PMID- 2875818 TI - Further evidence of the role of cyclic AMP as a mediator of the depressant effects of beta-adrenoceptor agonists and phosphodiesterase inhibitors on slow contracting mammalian skeletal muscles. AB - The depressant effects of beta-adrenoceptor agonists and phosphodiesterase inhibitors on contractions of slow-contracting mammalian skeletal muscles are associated with increased muscular cyclic AMP levels. A strong correlation was found to exist between the percentage depression of contraction and the percentage increase in cyclic AMP level, irrespective of the drug used and regardless of the mechanism of cyclic AMP production. The results strongly support the mediatory role of cyclic AMP in the depressant effects of beta adrenoceptor agonists and phosphodiesterase inhibitors on slow-contracting mammalian skeletal muscle contractions. PMID- 2875816 TI - Acute systemic and regional hemodynamic effects of alpha 1-adrenoceptor blockade in conscious spontaneously hypertensive rats. AB - The acute hemodynamic effect of the selective alpha1-antagonist, 2-[4-(n-butyryl) homopiperazine-1-y1]-4-amino-6,7-dimethoxy-quinazoline (bunazosin; E-643), was studied by the microsphere technique in 62 conscious spontaneously hypertensive rats. We found that a large fall in total peripheral resistance with a moderate increase in cardiac output accounted for the moderate decrease in arterial pressure; the heart rate did not change; the skeletal muscle, brain, heart, and gastrointestinal tract sensitively dilated, and kidney less sensitively dilated, their resistance vessels, with little change in their blood flow. PMID- 2875819 TI - Acute and chronic pulmonary thromboembolism: current perspectives. Part II: Etiology, pathology, pathogenesis, and pathophysiology. PMID- 2875820 TI - Hematopoietic stem cells for the treatment of genetic disease. PMID- 2875821 TI - Pharmacokinetics and effects of intravenous infusion of somatostatin in normal subjects--a two-compartment open model. AB - A direct radioimmunoassay of plasma somatostatin-like immunoreactivity (SRIF-LI) was developed and validated. The sensitivity was 16.0 pg/ml, and the specificity was good. The recovery of plasma SRIF-LI was 98.8 +/- 6.3%. The Scatchard plot of the antiserum binding data revealed a straight line, with a binding affinity of 3.52 X 10(-12) M and a binding capacity 4.06 X 10(-10) M. Synthetic SRIF (Stilamin), 250 micrograms, was infused intravenously over a 30-min period in 9 healthy volunteers. Plasma glucose, insulin (IRI), glucagon (IRG) and SRIF-LI were measured. A two-compartment open model was adopted to analyze the pharmacokinetic data of SRIF-LI. The results showed that plasma SRIF-LI rose from 192.2 +/- 16.2 pg/ml to a plateau of 2,129.8 +/- 288.2 pg/ml within 5-10 min after starting the infusion. The half disappearance time from plasma (Ta1/2) was 1.36 +/- 0.18 min, the half disappearance time from the 'remote' compartment (Tb1/2) was 49.6 +/- 10.9 min and the net half disappearance time from the two compartments together (Tn1/2) was 9.19 +/- 1.49 min. The metabolic clearance rate was 50.3 +/- 7.0 ml/kg/min. The plasma IRI, IRG and the IRI/IRG molar ratio were all suppressed during the infusion period. The recovery time of plasma IRG was mildly delayed in comparison to that of IRI. This indicates that there are dissociations between IRI and IRG in the extent and the duration of suppression caused by somatostatin infusion. PMID- 2875822 TI - Neurogenic hyperacute ascites in mice. AB - Four groups of mice were subjected to controlled fatal head trauma and then evaluated for the presence of ascites (neurogenic hyperacute ascites, NHA). The animals died virtually instantaneously and without evidence of maintained pain or suffering. The volume of ascites was determined in one group of animals. Two of the traumatized groups were pretreated, one with the beta-blocker propranolol and the other with the alpha-blocker phentolamine. A fifth, non-traumatized, group which was killed with either inhalation served as a control group. Two more groups of non-traumatized mice were administered either the alpha-adrenergic agonist methoxamine hydrochloride or the beta-agonist isoethrane mesylate before killing by ether inhalation, and then evaluated for ascites. Transudative ascitic fluid was found in 87-100% of untreated traumatized mice and in no control animals. Pretreatment with phentolamine had no effect on the prevalence of ascites. Pretreatment with propranolol produced a significant decrease in the prevalence of ascites compared with trauma alone (P less than 0.001). Isoethrane (beta-agonist) administration caused ascites in 100% of the treated animals. Methoxamine (alpha-agonist) administration did not cause ascites. A previously undescribed consequence of acute brain trauma is described (NHA) which appears to be mediated by beta-sympathetic activity of central origin. NHA is inhibited by beta-blockade and can be simulated with beta-agonist administration. PMID- 2875823 TI - [Use of cyclophosphamide in the treatment of polyarteritis nodosa]. PMID- 2875824 TI - Report of a wound infection caused by Vibrio parahaemolyticus and Vibrio vulnificus. AB - The present case describes a foot wound caused by a clam shell from which both Vibrio parahaemolyticus and Vibrio vulnificus were recovered. Although extraintestinal infections associated with Vibrio parahaemolyticus have been reported previously, the simultaneous isolation of two marine vibrios from our case suggests that these organisms may coexist in mixed infections from a common source. PMID- 2875825 TI - Effect of hypophysectomy on absorption of inorganic phosphate by the eel intestine. AB - Hypophysectomy of freshwater-adapted eels resulted in a marked reduction in net absorption of PO4(3-) in the non-stripped and non-everted intestine. Stanniectomy was without effect on net movements of water and electrolytes in this isolated eel preparation. Repeated injections of eel calcitonin into the eel, kept either in deionized water or 10 mM CaCl2, had no effect on net absorption of water and electrolytes, including Ca2+ and PO4(3-). In the stripped and everted intestine, the net PO4(3-) absorption was significantly greater in the fed eel than in the starved fish. Hypophysectomy of the fed eel resulted in a significant reduction, not only in PO4(3-) absorption, but also in absorption of water and other electrolytes. It is suggested that pituitary hormone is involved in the intestinal PO4(3-) absorption of the eel. PMID- 2875826 TI - Calcium-related abnormalities in fast and slow denervated skeletal muscle in rats. AB - Muscle weights, Ca-ATPase activity and calcium-binding proteins were studied after denervation in rat extensor digitorum longus (EDL) and soleus (Sol) muscles. Muscle weights decreased progressively as a function of denervation time: after 28 days EDL weight diminished by 70% and Sol weight by 47%. Ca-ATPase activity and calsequestrin were quite reduced in control Sol as compared to the control EDL. Denervation caused a considerable reduction in Ca-ATPase and calsequestrin in EDL, making it resemble the control Sol. PMID- 2875828 TI - Lithium in marine elasmobranchs as a natural marker of rectal gland contribution in sodium balance. AB - Natural concentrations of lithium in blood plasma and urine of several species of elasmobranchs and teleosts from the Black Sea and in rectal gland fluid of the former were determined by mass-spectrometric isotope dilution techniques. Unlike the teleosts, the elasmobranchs showed a prominent shift of Li/Na ratio in blood plasma with respect to the surrounding water, the plasma Li/Na ratio being five times lower than that of sea-water. Li-Na selectivity was found to be high in the kidneys and negligible in the rectal gland. Differences in Li-Na selectivity between kidneys and rectal gland are used as a basis for the method of estimation of relative contributions of these excretory organs in sodium excretion. Permanent contributions of the kidneys and rectal gland in sodium excretion of the ray Dasyatis pastinaca were found to be nearly equal. PMID- 2875827 TI - Atomic emission and proton microprobe studies of the ion content of otoliths of chinook salmon aimed at recovering the temperature life history of individuals. AB - Atomic emission experiments on whole otoliths of the chinook salmon (Oncorhynchus tshawytcha) show that a statistically significant relationship exists between otolith ion content (Fr, Zn, Mn, Na, Sr, P), ambient temperature, body length and otolith weight amongst individuals maintained under controlled diet and water conditions. Direct proton microprobe studies confirm these results and suggest that it may be possible to recover the temperature life history of individual fishes from the otolith. PMID- 2875829 TI - Serum cortisol, glucose and lipids in plaice (Pleuronectes platessa L.) exposed to starvation and aquarium stress. AB - Plaice were maintained in the aquarium (11-12 degrees C) during May for 15 days without feeding. Within 48 hr, there was a decline in serum total lipids (P less than 0.001), phospholipids (P less than 0.01), triglycerides (P less than 0.001), cortisol (P less than 0.01) and glucose (P less than 0.001), but an increase in nonesterified fatty acids (NEFA; P less than 0.01). There was a significant inverse correlation between NEFA and glucose over 15 days (P less than 0.001) and between NEFA and cortisol over the first 5 days (P less than 0.01). Cortisol and glucose showed a significant correlation over 15 days (P less than 0.01). Serum cortisol and glucose were not apparently affected by starvation. Only cortisol provided a sensitive indicator of aquarium disturbance. Exposure of the fish to agitation or reduced O2 for 1 hr significantly elevated cortisol (P less than 0.001) but only the latter treatment elevated glucose (P less than 0.01); neither treatment affected the lipids. PMID- 2875830 TI - Effect of monensin and nocodazole on the intestinal lipid esterification in mouse jejunal organ culture. AB - The ability of mouse jejunal explants to esterify a lipid emulsion containing oleic acid, palmitic acid and monopalmitin has been studied in different in vitro experimental conditions. The incubating lipid solution must have a minimum volume for obtaining optimal triglyceride esterification by the cultured intestinal mucosa. In our incubating conditions the exchange of oleic for palmitic acid does not significantly modify the amount of lipids esterified by the explants in 15 min. Monensin or nocodazole, added to the culture medium of intestinal explants for 3 hr, significantly change the amount of lipids esterified and secreted. The inhibition observed after nocodazole treatment disappears, however, when the explants are rinsed and the culture is allowed to continue for an additional 3 hr in a drug-free medium. These results suggest that the regulation of lipid metabolism can be studied in organ culture. PMID- 2875831 TI - Light at night cannot suppress pineal melatonin levels in the lizard Anolis carolinensis. AB - Up to 2 hr exposure of anoles to high intensity natural or artificial illumination at mid-dark does not suppress pineal melatonin levels. The results support the hypothesis that the lizard pineal is completely insensitive to acute exposure to light at night which is in direct contrast to the effects of light in higher vertebrates. PMID- 2875832 TI - The hypothalamo-hypophyseal system of Rana temporaria under osmotic stimulation with special reference to the hypothalamo-median eminence-distal lobe axis. AB - The secretory activity of the hypothalamo-hypophyseal system in the frog Rana temporaria under conditions of dehydration has been studied histologically using two parameters, the amount of stained neurosecretory material and the amount of neurosecretory material labelled by a radioactive precursor. The results are indicative of an increased secretory activity of the hypothalamo-neural lobe system as a result of water deprivation. In addition the involvement of the preoptic nucleus-median eminence axis in osmoregulation is confirmed. The pattern of distribution of autoradiographic silver grains over the median eminence together with data from literature support the idea that mesotocine is involved in the regulation of the activity of the adenohypophysis. PMID- 2875833 TI - Pepsin in the toad Bufo marinus. AB - The macroscopic localization of pepsinogen in the upper gastrointestinal tract of the anuran Bufo marinus was studied by means of biochemical assay. The pH optimum of the anuran pepsin was determined to be 1.6. The effect of lowered ambient temperature on stored pepsinogen and proteolytic activity was studied. Both parameters were reduced. The results are extrapolated to speculate on the mechanisms of gastric brooding in gastric brooding frogs of the genus Rheobatrachus. PMID- 2875834 TI - Decreased oxygen consumption after catecholamine-induced glycolysis in the alligator. AB - Anaerobic glycolysis was stimulated by forcing alligators to work to exhaustion, or by injecting them with epinephrine or norepinephrine. In all three groups, plasma lactate increased to above 20 mM. In the work group, oxygen consumption increased three-fold. In the catecholamine experiments, oxygen consumption dropped almost to zero immediately and stayed at zero from 45 min to over 2 hr. Gradually oxygen consumption resumed, finally exceeding the control value, but only by 50%. It was concluded that catecholamine-induced glycolysis produced phosphate-bond energy greatly in excess of immediate need, and that this energy was stored until it was used by the tissue. No oxygen was used until the store was depleted. PMID- 2875835 TI - The time-course of appearance and net accumulation of horseradish peroxidase (HRP) presented orally to juvenile carp Cyprinus carpio (L.). AB - A sensitive enzyme-linked immunosorbent assay (ELISA) technique was used in order to determine horseradish peroxidase (HRP) uptake from the carp gut. HRP was detected in blood plasma and various tissues within 15 min of oral intubation. The time-course of net accumulation (uptake-degradation) over a 2 hr period was recorded. The presence of HRP reached a maximum in the body tissues approximately 1 hr after intubation and on a microgram/g wet weight basis the order of accumulation within the tissues was spleen greater than kidney greater than liver. The total organ accumulation (net) was in the order liver greater than kidney greater than spleen. PMID- 2875836 TI - Iron metabolism during lactation and suckling in a marsupial, the quokka (Setonix brachyurus). AB - The iron status and transfer of iron through the milk during lactation were determined in a marsupial, the quokka, Setonix brachyurus. Lactating animals were not anaemic and had similar liver and spleen non-haem iron values to non lactating female adult animals but about 40% less non-haem iron than male adults. The milk iron concentration was very high during the period of lactation when the young is confined to the pouch, averaging about 20 micrograms/ml (eight times the plasma iron concentration), but fell markedly at the time when the young commence to leave the pouch. Blood haemoglobin concentration increased during pouch life of the young to reach adult levels at about 180 days, and liver non-haem iron concentration increased during the same period to values nearly 20 times greater than in their mothers. After the young left the pouch the non-haem iron concentration fell rapidly to the adult level while haemoglobin concentrations were maintained. It is concluded that milk is an adequate source of iron during pouch life of the quokka and enables the animal to build up iron stores which can be utilized after leaving the pouch. PMID- 2875837 TI - Seasonal variations in the responses of luteal and follicular luteinizing hormone stimulated adenylyl cyclases to estradiol implants and implant removal in pseudopregnant rabbits. AB - Summer rabbits appeared to be less sensitive to the presence of exogenous estradiol or to the withdrawal of exogenous estradiol than were Winter rabbits. Suppression of the luteinizing hormone(LH)-stimulated adenylyl cyclase of corpora lutea by estradiol-filled silastic capsules, which resulted in serum estradiol concentrations approximately 3.8 X control (high level), appeared to be greater in Winter rabbits than in Summer rabbits. Both high level and low level (2.1 X control) estradiol implants suppressed follicular LH-stimulated adenylyl cyclase in Winter rabbits but neither size capsule had an effect in Summer rabbits. Serum LH concentrations were equally low in Winter rabbits using either high or low level estradiol implants, while only the high level implants caused a decrease in serum LH in Summer rabbits. Withdrawal of the exogenous estradiol caused a precipitous fall in serum progesterone concentrations in Winter rabbits; estradiol withdrawal in Summer rabbits was without effect. PMID- 2875838 TI - Effect of serial blood sampling on interpretation of estradiol-17 beta involvement in laying hen calcium metabolism. AB - Effects of long-term, low levels of exogenous estradiol-17 beta and dietary calcium on calcium metabolism and laying hen performance, and effects of serial blood-sampling, were studied. Significant 3-way (P less than 0.01) and 2-way (P less than 0.05) interactions involving sampling obscured possible main effects (Exp. 1); no main effects were found in absence of blood sampling (Exp. 2). Estradiol-17 beta appears to increase calcium utilization with very low dietary calcium only. Relatively small brachial vein samples taken only every 3-4 weeks have substantial confounding effects on interpretation of data. PMID- 2875839 TI - Evidence for a dissimilarity of chicken oviducts differentiated by diethylstilboestrol and oestradiol-17 beta: a study of progesterone-induced egg white protein (avidin) synthesis. AB - The growth and differentiation of chick oviducts were caused by daily diethylstilboestrol (DES) or oestradiol-17 beta (E2) injections, and the effects of these oestrogens on the progesterone-induced production of a biotin-binding egg-white protein (avidin) were studied. In the DES primed oviducts, but not in the E2 primed ones, both DES and E2 administered with progesterone potentiated avidin production 2 to 3-fold, even after 10-day oestrogen withdrawal. The results suggest that DES and E2 prime the avian reproductive target tissue differently. PMID- 2875840 TI - Adrenergic modulation of pancreatic glucagon and insulin secretion in goats. AB - Five goats were used to investigate adrenergic influences on the secretion of both glucagon and insulin. The secretion of glucagon was augmented via alpha adrenergic stimulation. The secretion of insulin was enhanced by stimulation of beta-adrenergic receptors and inhibited by alpha-adrenergic stimulation. PMID- 2875841 TI - Seminal plasma composition in budgerigars (Melopsittacus undulatus). AB - Seminal plasma composition was studied in budgerigars. Semen was obtained from adult male budgerigars by applying gentle pressure to both sides of the cloaca. Pooled samples were centrifuged at 15,000 g for 2 min, and the seminal plasma separated for biochemical analysis. Osmolality, Na+, K+, Cl-, pH, glucose and fructose values were determined. The biochemical composition of budgerigar seminal plasma obtained in this study was: Osmolality 329.9 +/- 14.5 mOs/kg; Na+ 158.6 +/- 8.4 mEq/l; K+ 16.39 +/- 6.24 mEq/l; Cl- 109.2 +/- 7.4 mEq/l; pH 8.20 +/ 0.18 glucose 4.25 +/- 0.96 mmol/l; fructose 0.59 +/- 0.29 mmol/l. The results are discussed in relation to the values reported for the domestic fowl. This forms part of a reproductive biology study of non-domesticated avian species. PMID- 2875843 TI - Ammonia absorption from different parts of chicken intestine and its quantitative evaluation in situ. AB - Ammonia was more rapidly absorbed from the ileum than the jejunum, and the lower the small intestine was, the more rapid was the absorption of lumen fluid. About 95% of ammonia-15N introduced into the intestinal sac having Meckel's diverticulum in the middle part disappeared in 30 min, of which 90% was recovered as non-protein-N in the blood of the mesenteric vein draining the sac and in the mucosa of the tested portion in 30 min. About 57% of ammonia which disappeared from the intestinal lumen was found as ammonia-N and 26% as other non-protein-N in the mesenteric blood. Maximal rates of appearance of total non-protein-15N and ammonia-15N in the mesenteric blood were found within 10 min and returned to the levels at 0-5 min in 30 min. PMID- 2875842 TI - The relationship of eel Anguilla anguilla (L.) body size, lipid, protein, glucose, ash, moisture composition and enzyme activity (aldolase). AB - Body composition: protein, lipid, ash, moisture; and enzyme activity (aldolase) were studied in European eels (Anguilla anguilla) of various sizes. The fish were brought to the laboratory as glass eels (0.35 g) and maintained under controlled conditions (23 degrees C) for one year. After one year of growth, various sizes (between 9 and 420 g) were found. Significant correlation coefficients of the equation W = a ln C + b (where W = body weight, in g; C = composition, % or activity, u; and a,b are constants) were found among the composition parameters: protein, lipid, glucose and aldolase. Relative amounts of protein, glucose, moisture, ash and aldolase activity were found to decrease with an increase in the weight of eels, but the percentage of fat was higher in large eels than in small ones. PMID- 2875844 TI - The osmotic concentration of parietal muscle of the hagfish Myxine glutinosa L., including estimates of free and bound constituents. AB - The principal osmotic constituents of plasma and of muscle before and after ultracentrifugation have been determined. By analysing the muscle fluid and centrifuged muscle and determining their extracellular fluid (inulin space), ion binding in the cells was estimated at Na 26%, K 0.3%, Ca 93%, Mg 24%, Cl 21% and P 10%. Muscle fluid was 4.9% (2.7-7.4%) hyperosmotic to plasma. This is discussed in relation to calculated osmolality of muscle and plasma. PMID- 2875845 TI - Negative chronotropic effects of thyroxine on the isolated bullfrog heart. AB - An acute application of L-thyroxine (T4) to everted sinus-atrium preparations of bullfrog showed negative chronotropic effects consisting of two processes: an initial peak at 2-5 min and a delayed plateau at 40-60 min. The initial effect was blocked by Cd2+ and tetraethyl-ammonium (TEA). The delayed effect was suppressed by Cd2+ and NaCN. PMID- 2875846 TI - Electrophoresis in the study of diets and digestive rates of seabirds. AB - Attempts were made to identify unknown gut contents of seabirds by protein analysis using electrophoresis. Standards of undigested fish and squid muscle tissue were compared with muscle tissue at various stages of digestion. Digested mixtures of squid (Loligo reynaudi), Pelagic Goby (Sufflogobius bibarbatus) and Cape Anchovy (Engraulis capensis) did not resemble the undigested standards of each species respectively. Electrophoresis could prove useful in the study of differential digestion rates of seabird prey species. PMID- 2875847 TI - Oxygen consumption during embryonic development of the annual fish Nothobranchius korthausae with special reference to diapause. AB - The oxygen consumption of Nothobranchius korthausae eggs in different developmental stages, including diapause II and III, was measured. Oxygen consumption increases exponentially during embryonic development. In diapause II and III there is a drop in oxygen consumption, which attains a minimal level in diapause II after 3 weeks and in diapause III after 2 weeks. During early development the embryos can escape from hypoxic stress by entering diapause I and II. During late embryogenesis embryos in diapause III can escape from hypoxic stress by hatching. We conclude that survival of annual fish embryos is enhanced during conditions of low oxygen concentration by reduced oxygen consumption rates during diapause. PMID- 2875848 TI - Metabolic depression and heat balance in starving Wistar rats. AB - Resting metabolic rate and heat balance was studied in rats starved for 8 days at ambient temperature 22 degrees C and 30 degrees C. A depression of the resting metabolic rate was observed, at both temperatures. Metabolic rate depression, expressed as a function of the ratio between the real body wt and the normal body wt, was less at 22 degrees C than at 30 degrees C. Deep body temperature decrements of 2 degrees C and 0.6 degrees C by the end of starvation indicated that central temperature controlling mechanisms were affected. Concurrent decrements of evaporative heat loss did not account for the changes in heat conductance, thus indicating that a reduction of peripheral blood circulation also took part. PMID- 2875849 TI - Comparison of lysyl oxidase from bovine lung and aorta. AB - A prior report had concluded that bovine lung lysyl oxidase displayed an unusual resistance to inhibition by beta-aminopropionitrile (BAPN) in contrast to the enzyme isolated from other connective tissues. Therefore, lysyl oxidase was purified from fetal bovine lung and from aorta of young calves by parallel procedures, and key chromatographic and catalytic properties of these enzymes were directly compared. The enzymes prepared from both tissues each demonstrated the same multiplicity of enzyme species which resolve on DEAE-cellulose and otherwise demonstrated the same chromatographic behavior on gel exclusion media and on collagen-Sepharose and Cibacron blue-Sepharose columns. The activities of the unresolved but partially purified enzyme species of lung and of aortic lysyl oxidase were each fully inhibitable by approximately the same low (mu molar) concentrations of BAPN. Thus, the enzymes of both tissues were found to be very similar to each other by several criteria. PMID- 2875850 TI - Assignment of a processed mouse Aprt pseudogene to the same chromosome as the functional gene. AB - A novel genetic system has been used to demonstrate that a processed adenine phosphoribosyltransferase (Aprt) pseudogene is located on mouse chromosome 8, which is the same chromosome that carries the functional Aprt gene. A restriction fragment length polymorphism associated with the pseudogene was found to segregate concordantly with chromosome 8 in APRT- mutants of a near-diploid cell line that had lost one copy of the chromosome. PMID- 2875851 TI - Regional assignment of the erythropoietin gene to human chromosome region 7pter-- -q22. AB - The chromosomal location of the human gene for erythropoietin (EPO) was determined by Southern blot hybridization analysis of a panel of human-mouse somatic hybrid cell DNAs. DNAs from cell hybrids containing reduced numbers of human chromosomes were treated with the restriction enzyme PstI and screened with a cloned human EPO cDNA probe. EPO is assigned to human chromosome 7 based on the complete cosegregation of EPO with this chromosome in all 45 cell hybrids tested. A cell hybrid containing a translocated derivative of chromosome 7 localizes EPO to 7pter----q22. A HindIII restriction fragment length polymorphism is detected by hybridization of the EPO cDNA probe to human genomic DNA. PMID- 2875852 TI - The murine Hox-2 cluster of homeo box containing genes maps distal on chromosome 11 near the tail-short (Ts) locus. AB - Two probes derived from a mouse recombinant lambda-clone (H24.1), that contains a sequence closely homologous to the Drosophila antennapedia homeo box, were mapped to mouse chromosome (MMU) 11 by filter hybridization of somatic cell hybrid DNA. This sequence is highly homologous to a human homeo box gene (HOX2) and appears to represent one of the two genes in the Hox-2 cluster previously assigned to MMU 11. To regionally map the Hox-2 cluster, we have carried out in situ hybridization of the two H24.1 probes and of an independently isolated Hox-2 probe. The autoradiographic silver grain distributions were similar in all three experiments with a peak over band 11D. This region contains the locus for the tail-short (Ts) mutation which causes skeletal abnormalities in heterozygotes and early embryonic death in homozygotes. PMID- 2875853 TI - Susceptibility of Clostridium perfringens type A to 23 antimicrobial drugs. AB - A total of 106 strains of Clostridium perfringens type A, that had been isolated very recently from faecal cultures of healthy adults, were examined for susceptibility to 23 antimicrobial drugs (agar dilution method). All strains were susceptible to ampicillin, cefazolin, cefotaxime, cefotetan, cefoxitin, ceftriaxone, ciprofloxacin, fusidic acid, imipenem, metronidazole, mezlocillin, ofloxacin, penicillin G, piperacillin, teicoplanin, and vancomycin. Teicoplanin and imipenem were the most active, whereas fosfomycin and tetracycline were the least active drugs. Three of the 106 strains revealed multiple drug resistance against clindamycin, erythromycin, josamycin, tetracycline, and, in one instance, against chloramphenicol. PMID- 2875854 TI - [Assessment of the diagnostic value of gamma-GT isoenzyme in hepatocellular carcinoma]. PMID- 2875855 TI - [Narcotics combined with low-flow nitrous oxide in open-heart surgery]. PMID- 2875856 TI - Serum gamma-glutamyl transpeptidase activity in patients receiving chronic phenytoin therapy. AB - To better define the incidence and range of elevated gamma-glutamyl transpeptidase (GGT) activity in patients taking a drug known to induce hepatic microsomal enzymes, GGT was measured in the sera of 58 patients before and after six months of phenytoin therapy. Enzyme activity at six months was greater than baseline in 52 of 58 patients (90%). GGT activity (normal, 0-50 units/liter) was 45.2 +/- 9.9 (mean +/- SEM) at baseline and 135.8 +/- 18.1 after six months of therapy, a mean threefold increase (P less than 0.001). Of the 45 patients with normal baseline GGT activity, some had marked elevation of serum GGT activity with values rising over 200 units/liter in eight patients and over 300 units/liter in four patients. Mean serum GGT activity remained significantly elevated at 12 and 24 months. This elevation in GGT activity was not influenced by age, sex, or additional anticonvulsant drug therapy. Both baseline and six month GGT activity was lowest in patients who drank no alcohol, higher in patients who drank 0-1 pint/week, and greatest in patients who drank greater than 1 pint/week. All 13 patients with elevated baseline GGT activity were regular users of alcohol and/or taking other enzyme-inducing drugs. In conclusion, increase in serum GGT activity occurs in 90% of patients on long-term phenytoin therapy, most often to moderate but occasionally to high levels, and this rise in GGT activity is accentuated by regular consumption of alcohol. PMID- 2875857 TI - Chronic hypnotic efficacy of estazolam. AB - The chronic hypnotic efficacy of estazolam 2.0 mg was studied in five female and seven male subjects. Subjects with a complaint of insomnia verified by polysomnography were included in the study. Following a screening and adaptation period, subjects spent two consecutive nights a week in the laboratory. The protocol for medication was placebo for weeks 1, 2, 9 and 10 and estazolam for weeks 3-8. Estazolam 2.0 mg significantly improved sleep onset and total sleep time for up to six weeks of nightly administration without consistent recovery effects upon discontinuation. PMID- 2875859 TI - The influence of antihistamine compounds on the oral intake of different addictive drugs. AB - The influence of two antihistamines on the oral intake of various drugs with addictive potency was investigated in rats. Under the chosen conditions neither tripelennamine nor diphenhydramine have reinforcing properties. The reinforcing potency of addictive drugs is not augmented by the both substances. On the contrary, in some cases they led to a decrease in oral intake of the drug solutions offered. PMID- 2875858 TI - Dose effects of temazepam tablets on sleep. AB - The dose effects of temazepam tablets (15 and 30 mg) were studied at two sleep centres in 48 volunteers who had objective polysomnographic evidence of sleep onset insomnia. Volunteers slept in the laboratory, retiring at their usual bedtime after taking placebo or temazepam 30 min earlier, and were monitored for 8 h using standard polysomnographic techniques. Acute (nights 5-7) and short term (nights 11-13) temazepam, both 15 and 30 mg, improved the sleep of these volunteers by reducing sleep latency and increasing sleep time compared to the placebo baseline (nights 2-4). Dose differences were found primarily on the measurement of sleep staging, with 30 mg having a greater or more consistent effect than 15 mg. No residual effects were observed on the basis of questionnaires and objective tests of performance and no consistent evidence of disturbed sleep after discontinuing treatment was seen. PMID- 2875860 TI - Urticaria and angioedema. PMID- 2875861 TI - [Professional compulsory education for trainee physicians' assistants outside of vacation time]. PMID- 2875862 TI - [Acute beta blocker poisoning]. PMID- 2875863 TI - Effects of chronic intake of diazinon on blood and brain monoamines and amino acids. AB - Male rats were treated bi-weekly by gavage with the equivalent of 0.5 mg X kg-1 X day-1 technical diazinon for up to 28 weeks. The animals were sacrificed at specific time intervals (7, 14 and 28 weeks) and compared with age matched controls. Blood and brain tissues were analysed for cholinesterase activity and for concentrations of catecholamines and amino acids. Only Plasma cholinesterase was significantly reduced by the low level pesticide treatment. Erythrocyte acetyl cholinesterase and brain acetyl cholinesterase were unchanged while during the same period several putative brain neurotransmitters aspartate, glutamate (excitatory) and taurine as well as GABA (inhibitory) were significantly reduced in experimental vs control animals whereas no significant changes occurred between weeks in similarly fed animals. Blood serotonin was significantly elevated but no other blood or brain monoamine was significantly altered. Overt manifestations of brain toxicity observed were not apparent in experimental compared with control animals save for a significant decrease in growth observed in experimental animals. It was concluded that oral administration of low doses of diazinon exerts significant effects other than as an anticholinesterase on important brain neurotransmitters even at the low dose levels administered in this study. PMID- 2875865 TI - [Beta-adrenergic receptors in the brain, molecular mechanisms and regulation]. PMID- 2875866 TI - [Hypothalamic corticotropin-releasing factor--its endocrinological, biochemical and pharmacological aspects]. PMID- 2875864 TI - Famotidine. Pharmacodynamic and pharmacokinetic properties and a preliminary review of its therapeutic use in peptic ulcer disease and Zollinger-Ellison syndrome. AB - Famotidine is a new histamine H2-receptor antagonist. On a weight basis, famotidine is 20 times more potent than cimetidine and 7.5 times more potent than ranitidine in inhibiting basal and pentagastrin-stimulated gastric acid secretion in humans. Therapeutic trials have shown that famotidine 20 mg twice daily or 40 mg at bedtime may be an effective alternative to standard doses of cimetidine for healing gastric ulcers and to standard doses of cimetidine and ranitidine for healing duodenal ulcers. When used prophylactically, a single 20 mg dose of famotidine at night decreases the incidence of duodenal ulcer recurrence (versus placebo). However, further study is needed to clarify the comparative efficacy of the H2-receptor antagonists, in particular as maintenance therapy for healed peptic ulcer. Preliminary results in a few patients with Zollinger-Ellison syndrome indicate that famotidine, alone or in combination with an anticholinergic agent, gives good control of gastric acid hyperacidity with no evidence of biochemical or haematological toxicity. Famotidine appears to be well tolerated. Unlike cimetidine, it does not have antiandrogenic effects or alter hepatic metabolism of drugs. However, wider clinical experience with famotidine is needed to accurately determine its relative tolerability compared with other anti-ulcer drugs. Thus, famotidine appears to be a suitable and well tolerated alternative to cimetidine and ranitidine for healing peptic ulcers, but wider clinical experience is needed to assess its relative efficacy and tolerability in the long term maintenance treatment of patients with healed ulcers as well as in patients with Zollinger-Ellison syndrome. PMID- 2875867 TI - Trophic effects of somatostatin on calcium flux: dynamic analysis and correlation with pituitary hormone release. AB - Somatostatin (SRIF) modulates many aspects of normal physiology, appears useful as a potent antineoplastic agent, and may influence the development of degenerative brain disorders such as Alzheimer's disease. Regulation of cellular calcium flux by SRIF may contribute greatly to many of these interactions, yet remains controversial. SRIF rapidly causes a sustained inhibition of fractional calcium efflux from prelabeled dispersed rat pituitary cells (IC50, approximately 40 pM) and evokes a large rebound increase in efflux after the infusion, each coinciding temporally with expected physiological effects on GH release. These data support a particular role for SRIF-regulated calcium flux in the normal pulsatile pattern of GH secretion and a more general role in the varied biological actions of the peptide. PMID- 2875868 TI - Regulation of gene expression in rat hepatocytes and hepatoma cells by insulin: quantitation of messenger ribonucleic acid's coding for tyrosine aminotransferase, tryptophan oxygenase, and phosphoenolpyruvate carboxykinase. AB - The effect of insulin on the abundance of mRNAs coding for tyrosine aminotransferase (TAT; EC 2.6.1.5), tryptophan oxygenase (TO; EC 1.13.1.12), and P-enolpyruvate carboxykinase(GTP) (PEPCK; EC 4.1.1.32) was examined in primary cultures of adult rat hepatocytes and in FTO-2B rat hepatoma cells by Northern blot analysis using RNA probes made from SP6-cDNAs. Insulin (10(-11)-10(-7) M), which has been reported to induce TAT and decrease the activity of TO, did not change the levels of TAT mRNA and TO mRNA in hepatocytes regardless of the presence of other inducers. In the same cells, dexamethasone increased TAT mRNA up to 19-fold and TO mRNA up to 15-fold, and 8pClPhS-cAMP (CPT-cAMP) raised the level of TAT mRNA up to 36-fold. The abundance of TO mRNA was not altered by CPT cAMP. In contrast to TAT mRNA and TO mRNA, the level of PEPCK mRNA was dramatically decreased by insulin in the same hepatocytes. The sensitivity to this inhibitory effect of insulin was enhanced by dexamethasone and reduced by CPT-cAMP. FTO-2B hepatoma cells, which do not express detectable levels of TO mRNA, showed responses similar to those of hepatocytes, except that insulin caused a moderate reduction in TAT mRNA, but only in the presence of CPT-cAMP. The PEPCK mRNA in FTO-2B cells was suppressed by insulin in a manner closely resembling the effects in hepatocytes in the present study and in H4IIE hepatoma cells previously reported. PMID- 2875869 TI - Imaging and uptake mechanism of 131I-meta-iodobenzylguanidine in medullary thyroid carcinoma. AB - 131I-meta-iodobenzylguanidine (131I-MIBG) was also taken up by medullary thyroid carcinoma (MTC) as well as by pheochromocytoma in two patients with Sipple's syndrome. However, the mechanism of 131I-MIBG uptake by MTC has not been clarified yet. We measured tissue catecholamine levels in three MTC, since MTC can produce several active substances. Catecholamines were detected in various amounts in all MTC, but not in normal thyroid tissues. These findings suggest that MTC can produce catecholamines and therefore, 131I-MIBG is taken up and stored in catecholamine vesicles of MTC, like pheochromocytoma and neuroblastoma. We conclude that 131I-MIBG may be applied not only to diagnosis but also for the treatment of patients with MTC. PMID- 2875871 TI - Kinetics of ATP hydrolysis catalyzed by isolated TF1 and reconstituted TF0F1 ATPase. AB - The rate of ATP hydrolysis catalyzed by isolated TF1 and reconstituted TF0F1 was measured as a function of the ATP concentration in the presence of inhibitors [ADP, Pi and 3'-O-(1-naphthoyl)ATP]. ATP hydrolysis can be described by Michaelis Menten kinetics with Km(TF1) = 390 microM and Km (TF0F1) = 180 microM. The inhibition constants are for ADP Ki(TF1) = 20 microM and Ki(TF0F1) = 100 microM, for 3'-O-(1-naphthoyl)ATP Ki(TF1) = 150 microM and Ki(TF0F1) = 3 microM, and for Pi Ki(TF1) = 60 mM. From these results it is concluded that upon binding of TF0 to TF1 the mechanism of ATP hydrolysis catalyzed by TF1 is not changed qualitatively; however, the kinetic constants differ quantitatively. PMID- 2875872 TI - Early exercise testing after coronary care for suspected unstable coronary artery disease--safety and diagnostic value. AB - The safety of and the diagnostic information provided by a predischarge exercise test performed 2-7 days after admission to the coronary care unit (CCU) was evaluated in 400 patients less than 65 years of age with suspected unstable coronary artery disease, i.e. probable or definite non-transmural myocardial infarction, progressive angina pectoris or recurring chest pain of recent onset ('new chest pain'). No serious complications occurred. Signs of ischaemia during exercise tests were more common in older than in younger men and more often found in subjects with than without pathological findings in resting ECGs in the CCU. Above 45 years of age, more than half of the men with progressive angina or non transmural MI had SI depression greater than or equal to 2 mm and/or limiting chest pain, whereas men less than 45 years of age had a 10-25% incidence of corresponding findings in the test. In women above 55 years with progressive angina or non-transmural MI, 30-35% had ST depression and/or limiting chest pain at the test while 20-30% of women below 55 years of age had similar findings at the test. Beta-adrenoceptor blockade was used by half of the patients but did not seem to conceal signs of severe ischaemia. Thus a predischarge exercise test can be performed safely in patients with suspected unstable coronary artery disease in order to support or reduce the suspicion of severe disease. PMID- 2875870 TI - Two overlapping genes in bovine mitochondrial DNA encode membrane components of ATP synthase. AB - Two hydrophobic proteins have been purified to homogeneity from a mixture of about 13 proteins that are extracted from bovine mitochondria with a chloroform:methanol mixture. Sequence analysis shows that the smaller is a protein of 66 amino acids and is the product of a mitochondrial gene, A6L. The larger, a protein of 226 amino acids, is ATPase-6, a membrane component of ATP synthase, also encoded in mitochondrial DNA. The protein sequences determined establish that the genes for the two proteins overlap by 40 bases and indicate that translation of the second gene, ATPase-6, is initiated within the coding region of A6L. The A6L and the ATPase-6 proteins have also been isolated from the ATP synthase complex and so appear to be bona fide components of the enzyme. The function of A6L is unknown. However, weak structural homology suggests a functional similarity to the yeast mitochondrial protein, aapI, which is required for assembly of the fungal ATP synthase complex. Homologies between ATPase-6 and subunit a of the Escherichia coli ATP synthase complex indicate that the ATPase-6 protein has a similar role in the mitochondrial complex to its bacterial counterpart, being essential for the formation of an active proton channel. PMID- 2875873 TI - Critical appraisal of secondary prevention after myocardial infarction. What have beta-blockers to offer in the experimental situation? AB - This contribution reviews the beneficial effects of beta-adrenoceptor blocking drugs in experimental myocardial ischaemia (infarction). These effects include the ability to reduce early, life-threatening ventricular arrhythmias, improvement in ultimate long-term survival from an ischaemic insult with or without subsequent reperfusion and a reduction in the extent and degree of myocardial (and microvascular) ischaemic damage. Most of the evidence for protection, however, comes from studies in which drugs have been administered before the onset of ischaemia. Much less is known about the effects of intervening with beta-blocking drugs after the commencement of the ongoing infarction process. Although beta-blockers have a great deal to offer in the experimental situation there remains the strong possibility that other approaches might be able to offer even more. One promising approach is the combination of a beta-blocking drug with a specific inhibitor of thromboxane synthesis. PMID- 2875874 TI - A review of early intervention studies with beta blockers in patients with myocardial infarction. PMID- 2875875 TI - Late intervention studies with beta-blocking drugs in myocardial infarction: a critical appraisal. AB - Immense therapeutic effort has been devoted to testing the secondary preventative value of beta-blocking drugs in survivors of acute myocardial infarction. The failure to demonstrate a universally statistically significant benefit is ascribable to major inadequacies of design and technical errors in the majority of trials. Moreover, even in the very few trials in which survival benefit has been demonstrated, the ultra-selection of patients eventually included severely limits the general clinical application of their result. The specific subgroups of patients who derive most benefit and as importantly those that are disadvantaged by these drugs are ill-defined. Lack of comparative trials and absence of dose-response information also pose insuperable problems in attempting secondary prevention with beta-blocking drugs in practice. When to start these drugs to achieve maximum benefit and when to stop them to avoid long-term adverse reactions are major outstanding problems. The consequences of missed therapy are also unknown. Lack of a clinically discernible endpoint of success in the individual patient means that the physician's role is relegated to one of faith. Data so for available is insufficient to afford a rational change in therapeutic practice. However, these extensive studies have advanced understanding. They have clearly defined the design faults which must be avoided in future trials. They have made us aware that many post-infarct patients may not need beta-blocking drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875876 TI - Which patients for secondary prevention with beta-blocking drugs? PMID- 2875877 TI - Which patients for secondary prevention with calcium-antagonists? AB - Experimental studies have shown that calcium antagonists are beneficial in reducing myocardial damage following induced infarction and thus substantiate the concept that these drugs may influence reinfarction rate and death following myocardial infarction in man. Multicenter studies with verapamil and nifedipine are in progress but without conclusive results as yet. Which patients--if any- should receive calcium antagonists for secondary prevention after myocardial infarction remains an open question. The answer will depend on whether calcium antagonists are greater, equal or less effective than beta blockers for this purpose. If calcium antagonists should prove more efficacious than beta blockers, it would seem reasonable to give calcium antagonists preference for secondary prevention in those patients where contraindications to these drugs do not exist. If however, beta blockers prove the better alternative, they should be given preference unless beta blockers are contraindicated. The complex question of the future role of drugs in secondary prevention after myocardial infarction is by far not clarified and socioeconomic consequences as well as quality of life will have to be considered in context with drug influence on survival. PMID- 2875878 TI - Benefits and risks of drugs in secondary prevention of ischaemic heart disease--a summary. PMID- 2875879 TI - What is the economic impact of secondary prevention to society? AB - Of the 4.1 million population of Norway about 7500 patients between 20 and 75 years of age are admitted each year to hospital for acute myocardial infarction. Of these 1100 die in hospital, and 6400 are candidates for secondary prevention. On the basis of survival curves, we present a model for calculating potential benefits of secondary prevention. We use 'years of life gained' as a measure of outcome of secondary prevention. We consider three economic elements in secondary prevention: (a) Use of health services. The drug costs are moderate. The indirect costs are unknown, but probably moderate. (b) Resumed productivity is small. (c) Pensions and other transfers will increase the public expense. The net effect is an increase in public expense. Beta blockers reduce mortality by 25% and can be given prophylactically to about one third of the patients. So far, the effect is uncertain after two years. Secondary prevention for two years will cost Norway about 3.8 million NOK (526 000 US +) per year for drugs, give 597 extra survivors and provide 0.24 additional life years per patient treated. In case of life-long treatment and effect, the result will be 1.6 years of life per patient treated. About 50% of Norwegian patients smoke. If all the men stopped, there will be no costs, about 5120 extra survivors, and 3.3 additional years of life per patient who quits smoking. The effect is not limited in time. PMID- 2875880 TI - Interactions of stress hormones on lipid and carbohydrate metabolism in man with partial insulin deficiency. AB - The metabolic responses to 4-h infusions of adrenaline (3 micrograms kg-1 h-1) and cortisol (10 mg m-2 h-1 for 2 h followed by 5 mg m-2 h-1 for 2 h), separately and in combination, have been studied in six healthy subjects with concurrent somatostatin infusion (250 micrograms h-1). A combined infusion of adrenaline, cortisol, glucagon (180 ng kg-1 h-1) and somatostatin has also been studied. Somatostatin plus adrenaline and somatostatin plus cortisol resulted in hyperglycaemia (at 240 min, somatostatin plus adrenaline 11.4 +/- 0.4 mmol l-1, P less than 0.001; somatostatin plus cortisol 6.7 +/- 0.3 mmol l-1, P less than 0.05; somatostatin alone 4.9 +/- 0.4 mmol l-1). No synergistic effect on blood glucose was seen with adrenaline and cortisol together. When glucagon was added, blood glucose rose more rapidly than without glucagon (9.3 +/- 0.4 mmol l-1 v. 7.2 +/- 0.5 mmol l-1 at 45 min, P less than 0.001), but plateau values were similar. Plasma NEFA levels were raised by somatostatin plus adrenaline (0.55 +/- 0.04-1.82 +/- 0.11 mmol l-1 at 60 min). Somatostatin plus cortisol had no more effect on plasma NEFA than somatostatin alone. During the combined infusion of somatostatin plus adrenaline plus cortisol, a synergistic effect on plasma NEFA was observed (2.30 +/- 0.11 mmol l-1 at 60 min, P less than 0.01 v. somatostatin plus adrenaline). This occurred despite a small escape of insulin secretion. The lipolytic actions of adrenaline are potentiated by elevated circulating cortisol levels in insulin-deficient man.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875881 TI - 5-(2-Cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB): correlation of hypnotic and convulsant properties with alterations of synaptosomal 45Ca2+ influx. AB - Male ICR mice (20-35 g) were given either 5-(2-cyclohexylideneethyl)-5-ethyl barbituric acid (CHEB) alone (10-15 mg/kg i.p.) or CHEB (25-75 mg/kg i.p.) after a 1 h pretreatment with phenobarbital (75 mg/kg i.p.). CHEB alone (10 mg/kg) produced excitatory behavior but not convulsive seizures. Higher doses (11-15 mg/kg) produced convulsive seizures resulting in death. Pretreatment with phenobarbital prevented seizure activity. Following phenobarbital pretreatment, CHEB in doses of 50 and 75, but not 25 mg/kg, resulted in hypnosis of 53 +/- 16 and 64 +/- 9 min duration, respectively. In vitro, CHEB (10-200 microM) significantly inhibited 'fast-phase' (3 s) K+-stimulated 45Ca2+ uptake into cerebrocortical synaptosomes. CHEB (10 and 100 microM) also significantly increased basal 45Ca2+ uptake. The addition of CHEB (50 and 100 microM) or pentobarbital (100 microM) to striatal synaptosomes inhibited 'fast-phase' K+ stimulated 45Ca2+ uptake and endogenous dopamine release. CHEB (10-200 microM), but not pentobarbital (100 microM), produced a time- and dose-dependent increase in the resting release of endogenous dopamine from striatal synaptosomes. The results of this study show that CHEB possesses hypnotic activity if its lethal convulsant actions are blocked. The hypnotic actions of CHEB appear to correlate with inhibition of voltage-dependent calcium channels in brain synaptosomes. PMID- 2875882 TI - Correlation of the hypnotic potency of benzodiazepines with inhibition of voltage dependent calcium uptake into mouse brain synaptosomes. AB - Nine benzodiazepines were tested for their ability to inhibit 45Ca2+ uptake into mouse whole brain synaptosomes and for hypnotic activity as indicated by their ability to produce loss of the righting reflex. Eight of the benzodiazepines significantly inhibited fast-phase voltage-dependent 45Ca2+ uptake and five exhibited hypnotic activity. There was a direct correlation between the hypnotic potency of these five benzodiazepines and their ability to inhibit 45Ca2+ uptake. There does not appear to be a correlation between the anticonvulsant potency of the benzodiazepines and their potency for inhibiting 45Ca2+ uptake. These results support previous findings with other sedative/hypnotic drugs and suggest that inhibition of presynaptic calcium uptake may be linked with hypnotic but not anticonvulsant actions of benzodiazepines. PMID- 2875883 TI - Comparison of the effects of fenoldopam, SK & F R-87516 and dopamine on renal arterioles in vitro. AB - The ability of the selective DA1 agonists fenoldopam and SK & F R-87516 to relax norepinephrine-contracted afferent and efferent arterioles isolated from rabbit kidney was compared. In both arterioles, fenoldopam and SK & F R-87516 produced a concentration-dependent relaxation with a potency similar to that of dopamine. Fenoldopam also relaxed efferent arterioles contracted with angiotensin II. The selective DA1 receptor antagonist, SK & F R-83566, caused parallel displacements in the concentration-response curves to SK & F 82526, corresponding to dissociation constants of 10.5 and 8.3 nM for afferent and efferent arterioles, respectively. The results provide direct evidence that the dopamine receptor present on renal resistance vessels is of the DA1 subtype. PMID- 2875884 TI - Cardiovascular profile of pimobendan, a benzimidazole-pyridazinone derivative with vasodilating and inotropic properties. AB - Intravenous infusions of 0.01-0.1 mg X kg-1 X min-1 of pimobendan, a benzimidazole-pyridazinone derivative in pigs with normal coronary circulation caused dose-dependent changes in heart rate (10-35%), left ventricular systolic pressure (-5 to -45%), left ventricular filling pressure (-20 to -40%) but had only a minor effect on the maximum rate of rise of left ventricular pressure (max LVdP/dt; 10-20%). The decrease in mean arterial blood pressure was primarily due to systemic vasodilation; peripheral resistance and cardiac output decreased by up to 40 and 14%, respectively. Vasodilation occurred in several vascular beds, but was particularly pronounced in the adrenals, stomach, small intestine and myocardium. Although the increase in myocardial blood flow favoured the epicardium, vascular conductance in both the endo- and epicardial layers was significantly increased. Myocardial O2 consumption (MVO2) was not affected despite the increase in heart rate. Bolus injections of 0.1-0.5 mg X kg-1 pimobendan produced similar changes in all haemodynamic variables, except max LVdP/dt which now increased by 30-70%. As in the infusion experiments, cardiac output tended to decrease due to a pronounced reduction in ventricular preload probably as a result of venodilation and the consequent reduction in cardiac filling. However, in animals where max LVdP/dt and cardiac output were reduced and pre- and/or after-load were increased by partial occlusion of the left anterior descending coronary artery, pimobendan clearly increased both max LVdP/dt and cardiac output. Pretreatment with propranolol did not modify any of the cardiovascular responses to pimobendan, thereby excluding the involvement of a beta-adrenoceptor mechanism. Pimobendan is thus a compound with vasodilator and positive inotropic properties that improves cardiac output in animals with severe myocardial ischaemia. The finding that the mild tachycardia caused by pimobendan was not accompanied by an increase in MVO2 warrants investigation to evaluate its usefulness in the treatment of heart failure. PMID- 2875885 TI - Age-related decrease in endothelium-dependent dilator response to histamine in rat mesenteric artery. AB - The effect of aging on the vasodilator responses to histamine, 2 pyridylethylamine and 4-methylhistamine of ring segments of rat mesenteric arteries were investigated. The maximal extent of histamine-induced dilatation of the arteries previously contracted with norepinephrine was greatest for arteries from rats aged 2 and 8 weeks. The maximal response decreased progressively with an increase in age to 13 and 56 weeks. Arteries from 99 week old rats scarcely responded to histamine. Under these conditions, the dilatation induced by papaverine showed no change with age. The vasodilatation caused by 2 pyridylethylamine and 4-methylhistamine also decreased age dependently. The dilatation of the arteries induced by these agents was inhibited by the H1 antagonist chlorpheniramine, but not by the H2-antagonist cimetidine. Removal of the endothelium completely abolished the vasodilator effect of histamine, leaving the effect of papaverine unaffected. Hydroquinone and methylene blue reversed the dilatation induced by histamine, without affecting that caused by papaverine. These results suggest that the age-related decrease in dilatation of rat mesenteric artery in response to histamine is mainly due to a decrease in the ability of the endothelium to liberate a mediator(s). PMID- 2875886 TI - Major tranquillizers can be distinguished from minor tranquillizers on the basis of effects on marble burying and swim-induced grooming in mice. AB - The effects of psychotropic compounds on grooming and burying were compared in mice. Burying behaviour was provoked by glass marbles and grooming was observed after 3 min swimming. Compounds with minor tranquilizing properties, such as diazepam, chlordiazepoxide, flunitrazepam, clonazepam, meprobamate and ethyl alcohol, were more effective in reducing burying than grooming. Drugs with an anticholinergic effect, e.g. scopolamine and atropine were also more effective against burying. A number of neuroleptic drugs, such as haloperidol, chlorpromazine, perphenazine and trifluperidol reduced grooming more effectively than burying. Non-selective inhibitory effects were observed with clozapine, thioridazine, diphenhydramine, imipramine, mianserin and apomorphine. It is concluded that, with certain limitations, the burying-grooming test described offers a simple tool for identifying novel compounds as potential major or minor tranquilizers. PMID- 2875887 TI - The relationship between alterations in alpha 1-adrenoceptor reserve by phenoxybenzamine and benextramine and the sensitivity of cirazoline-induced pressor responses to inhibition by nifedipine. AB - Nifedipine does not inhibit the alpha 1-adrenoceptor-mediated pressor response of cirazoline at a dose that significantly antagonizes the alpha 2-adrenoceptor mediated pressor response of B-HT 933. After elimination of the alpha 1 adrenoceptor reserve with either phenoxybenzamine or benextramine, the response to cirazoline was rendered highly sensitive to antagonism by nifedipine. These results support the hypothesis that the resistance of alpha 1-adrenoceptor mediated pressor responses to inhibition by calcium channel antagonists may be caused by a large alpha 1-adrenoceptor reserve. PMID- 2875888 TI - The contractile action of palytoxin in the isolated rabbit urinary bladder. AB - Palytoxin at 10(-10)-10(-7) M caused contractions of the detrusor muscle from rabbit urinary bladder in a concentration-dependent manner. The response to palytoxin was markedly inhibited by indomethacin (a cyclooxygenase inhibitor) or nordihydroguaiaretic acid (a lipoxygenase inhibitor) at 10(-5) M. Indomethacin and nordihydroguaiaretic acid also inhibited the response to arachidonic acid at 10(-3) M. A Ca2+-free medium with EGTA or nifedipine at 10(-5) M, nearly abolished the responses to palytoxin and arachidonic acid. Tetrodotoxin, phentolamine, atropine and chlorpheniramine (all at 10(-5) M) had a slight or no inhibitory effect on the response to palytoxin. These results suggested that in the rabbit bladder, the contractile effect of palytoxin is mainly dependent on an increase in metabolites of arachidonic acid. PMID- 2875890 TI - Vascular beta-adrenoceptor blocking activity of endotoxin and pertussis toxin from Bordetella pertussis in rats. AB - Isolated and purified leucocytosis promoting factor (LPF), alternatively described as pertussis toxin, reduced the hypotension after beta 2-adrenoceptor stimulation with salbutamol as well as the negative chronotropic activity induced by the muscarinic receptor stimulant arecoline 4 days after its injection into rats. These inhibitory effects of LPF were accompanied by a reduction in basal blood pressure. No effect on autonomic responsiveness or blood pressure was observed 5 h after injection of LPF. Sublethal doses of purified B. pertussis endotoxin (LPS) elicited neither vascular beta 2-adrenergic nor cardiac cholinergic blockade 4 days following injection. Only a distinct vascular beta 2 adrenolytic effect was measured 5 h after pretreatment with the same doses of LPS. This beta 2-adrenoceptor hyporesponsiveness was accompanied by neither an anticholinergic nor a hypotensive effect, but rather by a slight but significant elevation of the blood pressure. In conclusion, both components of B. pertussis (LPS and LPF) give rise to vascular beta 2-adrenergic hyporesponsiveness irrespective of blood pressure effects. There is an important difference between both components with respect to their various kinetic profiles for this phenomenon: an early occurring and short-lasting beta 2-adrenergic blockade for LPS and a late occurring LPF-mediated beta 2-adrenergic blockade. PMID- 2875889 TI - Selective displacement of [3H]mepyramine from peripheral vs. central nervous system receptors by loratadine, a non-sedating antihistamine. AB - Displacement of [3H]mepyramine binding was compared in membranes from guinea-pig lung vs. cerebral cortex as a measure of affinity for peripheral vs. central nervous system (CNS) histamine receptors. Loratadine, a new non-sedating antihistamine, was found to be the only compound tested which was selective for lung (Ki = 35 nM) vs. cortex (Ki = 118 nM). This difference is statistically significant (P less than 0.05) whereas there was no significant (P greater than 0.05) difference in the Kis between the 2 tissues for terfenadine, astemizole, mequitazine or chlorpheniramine. It is concluded from these and other studies that the lack of significant sedative effects shown with loratadine is due to its poor penetration into the CNS and selectivity for peripheral histamine receptors. PMID- 2875891 TI - Conversion of kinins and their antagonists into B1 receptor activators and blockers in isolated vessels. AB - A carboxypeptidase inhibitor (DL-2-mercaptomethyl-3-guanidoethylthiopropranoic acid) (mergetpa) was used to block the conversion of kinins and B2 receptor antagonists into metabolites devoid of the C-terminal Arg. Experiments were carried out on rabbit isolated aortae (a B1 receptor system) or rabbit jugular veins and dog carotid arteries (two B2 receptor systems). The contractile effect of bradykinin in the rabbit aorta was significantly reduced by mergetpa while that of desArg9-BK was not modified. pA2 values of B2 receptor antagonists, [Thi5,8,D-Phe7]bradykinin and [Thi6,9,D-Phe8]kallidin were markedly reduced by mergetpa. The apparent affinity (pA2) of a B1 receptor antagonist, [Leu9]desArg10 kallidin was not affected. Carboxypeptidases inhibition did not modify the activities of bradykinin or the affinities of B2 receptor antagonists in the rabbit jugular vein and the dog carotid artery. An inhibitor of kininase II (D-3 mercapto-2-methylpropranoyl-L-proline (S,S] (captopril) reduced the contractile effects of angiotensin I in the three preparations and potentiated the stimulatory or inhibitory effects of bradykinin: captopril did not have effect on the affinities of B2 receptor antagonists and did not modify the effects of angiotensin II. Comparative experiments performed in tissues with or without endothelium gave the same results with both mergetpa and captopril. The present findings suggest that bradykinin and B2 receptor antagonists are converted by carboxypeptidases into biologically active B1 receptor agonist or antagonists. This is the reason why B2 receptor antagonists are not selective. PMID- 2875892 TI - Neuroeffector transmission in the guinea-pig internal anal sphincter: an electrical and mechanical study. AB - ATP (10(-7)-10(-4) M), ADP (10(-7)-10(-4) M), AMP (10(-7)-10(-4) M) and adenosine (10(-6)-10(-4) M) each hyperpolarized the membrane, inhibited spontaneous spike discharge and relaxed the guinea-pig internal anal sphincter. All experiments were carried out using intracellular microelectrode and simultaneous tension recording techniques in the presence of phentolamine (10(-6) M) and atropine (10( 6) M). ATP was the most effective and produced a concentration-dependent membrane potential change comparable in amplitude to that produced by field stimulation of non-adrenergic non-cholinergic (NANC) nerves. Inhibitory junction potentials, the accompanying relaxations and the responses to ATP (5 X 10(-6)-5 X 10(-5) M) were additive and were increased in K+-deficient and decreased in K+-rich solutions and inhibited by apamin (10(-7) M). A proteolytic enzyme, alpha-chymotrypsin (0.5 U/ml) preferentially antagonized the ability of vasoactive intestinal polypeptide (10(-7) M) to hyperpolarize the membrane and relax the sphincter. The electrical and mechanical responses to ATP (10(-5) M) and inhibitory nerve stimulation were only slightly reduced. The results are consistent with the view that ATP or a related adenine nucleotide may have a transmitter role in the guinea-pig internal anal sphincter. PMID- 2875894 TI - Enhancing effect of dopamine blockers on evoked acetylcholine release in rat striatal slices: a classical D-2 antagonist response? AB - The effects of chlorpromazine, pipotiazine, haloperidol, domperidone, sulpiride and SCH 23390 on the potassium-evoked release of [3H]acetylcholine [( 3H]ACh) were studied in rat striatal slices. All 5 dopamine (DA) antagonists with D-2 blockade efficacy induced an increase of [3H]ACh release whereas the specific D-1 antagonist SCH 23390 was devoid of significant effects. The maximal effect (about 100% increase) was obtained with haloperidol, pipotiazine and sulpiride but not with domperidone and chlorpromazine. Interestingly, sulpiride was found to exert an unexpected marked potency. The comparison of the activities of the 6 compounds on evoked ACh release to their affinities for D-2 receptors [( 3H]N propylnorapomorphine binding sites) indicates that the pharmacological profile of the dopamine receptor implicated in the regulation of ACh release cannot be superimposed on that of the classical D-2 receptor. Participation of DA presynaptic receptors could however explain the differences in efficacy observed with the compounds studied. PMID- 2875893 TI - The effects of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4 methylenedioxyamphetamine (MDA) on monoaminergic systems in the rat brain. AB - The effects of two amphetamine-like designer drugs, 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA), on dopaminergic and serotonergic systems in the rat brain were investigated and compared to those of methamphetamine (METH). Like METH, single or multiple 10 mg/kg doses of either drug caused marked reductions in both tryptophan hydroxylase (TPH) activity and concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid, in several serotonergic nerve terminal regions. In all regions examined, the reduction in 5-HT content corresponded to the depression of TPH activity. Unlike multiple METH administrations, which induced pronounced deficits in dopaminergic neuronal markers, repeated doses of MDA or MDMA did not alter striatal tyrosine hydroxylase (TH) activities or reduce striatal dopamine concentrations. A single dose of MDA or MDMA significantly elevated striatal dopamine content; however, after repeated drug administrations dopamine concentrations were comparable to control values. At this time, striatal levels of homovanillic acid were significantly elevated suggesting that both drugs influence dopamine turnover. The effects of MDA or MDMA administration in the rat brain are reminiscent of those elicited by p-chloroamphetamine, a presumed serotonergic neurotoxin. PMID- 2875895 TI - Characterization of a polypeptide associated with coated vesicles and the cytoskeleton which is recognized by a CREST serum. AB - Serum from an individual with the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dismotility, sclerodactyly, telangiectasia) reacts not only with kinetochores, but also with a cytoplasmic, phosphorylatable polypeptide, which is shown by immunofluorescence in whole cells and immunoelectronmicroscopy in sections to be associated with actin stress fibres in cultured mammalian cells. The antigen shows some variation in molecular weight between species, estimated by immunoblotting to range from 68 to 76 kD between mouse, Chinese hamster, sheep and human cells. Much of the polypeptide copurifies with coated vesicles, of which approx. 5% bound antibody from the serum, as detected by immunogold electronmicroscopy. PMID- 2875896 TI - Transglutaminase (TG) involvement in early embryogenesis. AB - Transglutaminase (TG) has been examined in different stages of preimplantation mouse embryogenesis. The specific activity of this enzyme in the soluble cellular fraction increases 2-fold from 2-cell embryos to 8-cell morulae and 4-fold from 2 cell embryos to blastocyst. The same developmental profile was seen when either N,N'-dimethylcasein or endogenous substrates were used in the TG assay. Using high-speed supernatants from different stage embryos as a source of enzyme and [3H]putrescine as acyl acceptor, the major acyl donor components were tubulin and a high molecular weight (HMW) cross-linkage product, as assessed by electrophoresis and immunoblotting. When either assembled or monomeric cytoskeleton proteins were compared as substrates, microtubules were the best acyl donors. These studies indicate that TG activity is modulated during the changing demands of blastomeres for microtubule cytoskeleton in early embryogenesis. PMID- 2875897 TI - Properties of PC12 pheochromocytoma cells transplanted to the adult rat brain. AB - The possibility of employing PC12 pheochromocytoma cells for transplantation into the rat brain as a substitute for adrenal chromaffin cells was examined. Cultured PC12 cells were implanted into the striatum of rats and examined after one day to 20 weeks by fluorescence histochemistry and immunocytochemical staining for tyrosine hydroxylase and a surface antigen of PC12 cells. Between 800 and 3000 cells survived the implantation procedure and persisted relatively unchanged for about one week. Long-term survival of small numbers of PC12 cells was observed in nine of 14 animals, although the number of surviving cells was reduced after 7.5 20 weeks as compared to earlier time periods. By 14-20 weeks after implantation, most of the remaining cells had developed processes. In other animals, there appeared to have been an initial large increase in the number of cells, followed by complete death of the graft. In many of these animals with no surviving cells, large deposits of hemosiderin were found at the implantation site, an apparent residue of earlier tumor growth. Thus in some animals, the number of PC12 cells apparently increased initially, but in these animals the graft was ultimately rejected. In other animals, small numbers of PC12 cells survived for up to 20 weeks, and many of these cells eventually developed neurite-like processes. Continued uncontrolled tumor growth was not observed. PMID- 2875898 TI - Hymenin, a novel alpha-adrenoreceptor blocking agent from the Okinawan marine sponge Hymeniacidon sp. AB - A novel bromine-containing alkaloid, hymenin, has been isolated from the Okinawan marine sponge Hymeniacidon sp. as a potent alpha-adrenoceptor blocking agent and its structure determined to be 1 on the basis of the spectral data. PMID- 2875899 TI - Morphological and enzymatic heterogeneity of suramin-induced lysosomal storage disease in some tissues of mice and rats. AB - Suramin-induced lysosomal storage disease reproduced in the rat was extended to the mouse with the attempt to characterize enzymatically and morphologically heterogeneous responses of various organs to the drug. Suramin administration strikingly decreased (3-6 days afterward) the activity of beta-glucuronidase in all tissues studied (kidney, liver, heart, and skeletal muscle). The enzymatic responses were small in the activities of beta-N-acetyl-glucosaminidase. The activity of arylsulfatase A decreased to a varying degree in mouse tissues, but in rats the activity increased in liver and skeletal muscle. The activity of cathepsin D increased in rat tissues. Suramin induced morphological changes characteristic to lysosomal storage diseases in kidney and liver but not in heart and skeletal muscle of both mice and rats. Kidney was appreciably more susceptible to suramin than liver. The occurrence of lysosomal accumulations, membranous lamellar inclusions, and granular material were most prominent in tubular cells of kidney and in Kupffer cells of liver. These cells also presented intensive Alcian blue staining. Interestingly, the enzymatic and morphological responses did not correlate with each other, which may reflect differences in the regulation of lysosomal functions in various cell types. PMID- 2875900 TI - [Neurochemical factors in the autoregulation of cerebral circulation]. PMID- 2875902 TI - [Peptide modulation of spontaneous and evoked catecholamine release in the caudal mesenteric ganglion of the dog]. AB - Oxytocin, vasopressin, melanostatin, bradykinin, LHRH-like peptide in different ways affected the spontaneous outflow and release of adrenaline and noradrenaline induced with central and peripheral nervous stimuli as well as with acetylcholine in the superfusate of the dog isolated inferior mesenteric ganglion. PMID- 2875901 TI - Isolation of a rat pineal gland cDNA clone homologous to tyrosine and phenylalanine hydroxylases. AB - A rat pineal gland cDNA expression library has been probed with an antiserum raised against rat tryptophan hydroxylase. A clone has been isolated and its sequence reveals a high degree of homology with those of tyrosine and phenylalanine hydroxylases. PMID- 2875903 TI - Mosquitoes of Goa. PMID- 2875904 TI - Terfenadine and brompheniramine maleate in urticaria and dermographism. AB - The effects of brompheniramine maleate (12 mg twice daily in sustained release form) and terfenadine (60 mg twice daily) on the symptoms and well-being of 16 adults with urticaria with or without dermographism were assessed by symptom questionnaire. Following an initial 2-week period without therapy, each drug was taken for 2 weeks in a randomised double-blind cross-over study. Both drugs produced significant relief of itch and rash but only brompheniramine produced significant drowsiness. Brompheniramine maleate was more effective than terfenadine in the patients with dermographism. PMID- 2875905 TI - Influence of streptozotocin upon the induction of tyrosine aminotransferase, the content of NAD and of 5-methyl cytosine in rat liver. AB - The antibiotic, streptozotocin, has carcinostatic, carcinogenic, and diabetogenic properties. Moreover, it is capable of inducing the enzyme tyrosine aminotransferase in a permanent line of rat liver cells. In the present publication, the effects of streptozotocin upon the induction of tyrosine aminotransferase, NAD synthesis, and methylation of DNA in different organs were analyzed in vivo. If administered alone, streptozotocin slightly induced tyrosine aminotransferase. The induction of tyrosine aminotransferase caused by tryptophan or nicotinamide was inhibited by streptozotocin. Streptozotocin reduced the NAD content of the liver. NAD synthesis induced by tryptophan was reduced by streptozotocin, while that induced by nicotinamide was enhanced. DNA methylation in the form of 5-methyl cytosine was not influenced by streptozotocin. PMID- 2875906 TI - Inositol phospholipids cause the activation of adrenal tyrosine hydroxylase through their electrostatic action on the enzyme. AB - The effects of inositol phospholipids on adrenal tyrosine hydroxylase (TH) were studied. Phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) caused a rapid and concentration dependent activation of TH in vitro. The potency of this activation was dependent on the number of phosphate groups in the lipid molecule, and the activation was completely suppressed by increasing the concentrations of salts in the reaction mixture. These results seem to indicate that the activation of TH by inositol phospholipids may be due to their electrostatic action, and suggest a possible involvement of inositol phospholipids in the regulation of TH activity in vivo. PMID- 2875907 TI - Temelastine, a new H1-receptor antagonist. AB - Temelastine is a selective, competitive histamine H1-receptor antagonist which does not penetrate the central nervous system. The effect of varying doses of temelastine was compared in a randomized, double-blind, controlled study by measuring the inhibition of cutaneous histamine wheals. In twelve subjects single oral doses of 50, 100 and 200 mg of temelastine produced dose-dependent reductions in wheal areas. The inhibition of wheal size was maximal by 2 hr after dosing and was present at 8 hr. At 2 hr the 50, 100, and 200 mg doses reduced the wheal size by 53, 64, and 78%, respectively. Chlorpheniramine, 4 mg, reduced wheal size by 32% at the same period. The ability of temelastine to antagonize the histamine-induced skin reaction over 20 hr was evaluated in a second randomized, double-blind study. Eight subjects participated. Temelastine, 100 mg, produced reductions of 64, 49, 56 and 51% in histamine wheal area at 8, 12, 16 and 20 hr, respectively. Plasma concentrations at these times were 4.04, 2.77, 1.88, and 1.44 mumol/l, respectively. These data suggest that blood levels as low as 1.44 mumol/l may be sufficient to produce an antihistaminic effect, and that daily or twice daily dosing with 100 mg may be adequate to control allergic symptoms. PMID- 2875908 TI - Differentiation-dependent expression of proteins in brain endothelium during development of the blood-brain barrier. AB - The blood-brain barrier is a specific property of differentiated brain endothelium. To study the differentiation of blood vessels in the brain, we have correlated the expression of a number of proteins in brain endothelial cells with the development of the blood-brain barrier in mouse, quail, and chick embryos. Using histochemical methods, alkaline phosphatase activity was found to be present in all species and appeared around embryonic Days 17 (mouse), 14 (quail), and 12 (chick). Butyrylcholinesterase activity was found in the mouse and quail but not the chick brain vasculature, and appeared around Days 17 (mouse) and 15 (quail). gamma-Glutamyltranspeptidase activity was demonstrated histochemically in mouse but not in chick and quail brain capillaries, beginning at Day 15. Transferrin receptor was localized on brain endothelium in all species by immunofluorescence methods using monoclonal antibodies. It appeared at Days 15 and 11 in mouse and chick embryonic brain, respectively. The staining of all markers in embryonic brain was compared with adult brain endothelium and the leptomeningeal blood vessels. The expression of these proteins was correlated with the development of the blood-brain barrier by studying the permeability of brain endothelium for the protein horseradish peroxidase during mouse embryogenesis. Vessels in the telencephalon were found to become impermeable around Day 16 of development. Taken together the results of previous investigations and those presented here, we conclude that a number of proteins are sequentially expressed in brain endothelial cells correlating in time with the formation of the blood-brain barrier in different species. PMID- 2875909 TI - Destruction of the preganglionic nerves by beta-bungarotoxin does not interfere with normal embryonic development of the rat adrenal medulla. AB - Using beta-bungarotoxin (beta-BTX) as a tool to eliminate the preganglionic cholinergic nerve supply to the embryonic rat adrenal gland, we have investigated whether or not these nerves affect the differentiation of embryonic chromaffin cells (pheochromoblasts). Rat fetuses received a single injection of 1 or 2 micrograms beta-BTX or an identical volume of saline at embryonic day (E) 17 and were taken for morphological and biochemical analyses at E 21. Administration of beta-BTX caused a 15 to 20% reduction in body weight, crown-rump-length and adrenal weight. Spinal cord development was reduced and acetylcholinesterase positive cells in ventral and lateral columns were virtually absent in toxin treated animals. In adrenal glands, a decrease of choline acetyltransferase activity to 13% of control levels and a concomitant decrease of ultrastructurally identifiable nerve fibers and axon terminals revealed that application of 2 micrograms beta-BTX effectively reduced the neuronal input to E 21 adrenal glands. Values for total adrenal catecholamines, relative amounts of adrenaline and noradrenaline, tyrosine hydroxylase and phenylethanolamine N methyltransferase activities were unaltered. All ultrastructural features of pheochromoblasts (except the lack of synapse-like axon terminals) were inconspicuous. Corticosterone levels in adrenals and plasma were identical to controls. These data strongly suggest that normal embryonic development of adrenal chromaffin cells does not require an intact nerve supply. PMID- 2875910 TI - New alpha 2-adrenergic blocker (DG-5128) improves insulin secretion and in vivo glucose disposal in NIDDM patients. AB - Effects of oral administration of DG-5128, a new oral hypoglycemic agent, on glycemic control after a mixed meal and an in vivo glucose disposal were measured in subjects with nonobese non-insulin-dependent diabetes mellitus (NIDDM). Oral administration of DG-5128 significantly (P less than .05) enhanced insulin secretion both 30 and 60 min after a mixed meal (550 kcal), with a concomitant decrease in postprandial plasma glucose levels at 60 and 120 min. Glucose disposal rate between the 2nd and 4th h of a euglycemic insulin clamp, developed through a constant infusion of insulin (0.77 mU X kg-1 X min-1) together with somatostatin (80 ng X kg-1 X min-1), was 2.5-fold higher in a DG-5128-treated group (P less than .01) than in a control group. However, there was no difference between the two groups in either plasma glucose concentration or plasma insulin concentration at either the 2nd or the 4th h. These results indicate that DG-5128 is effective in controlling plasma glucose levels in subjects with NIDDM by stimulation of both insulin secretion and in vivo glucose disposal. PMID- 2875911 TI - Immunohistochemical colocalization of GABA and insulin in beta-cells of rat islet. AB - gamma-Aminobutyric acid (GABA) is found in high concentrations in the pancreatic islet. In addition, enzymes regulating the level of GABA (L-glutamate decarboxylase and GABA-alpha-ketoglutarate transaminase) have been immunohistochemically localized in the medullary cells of the islet. In this study, an immunofluorescence and elution/restaining protocol is used to determine the distribution of GABA and either insulin, glucagon, or somatostatin in a tissue section. GABA was not detected within the islet alpha- or delta-cells but was determined to be localized within the insulin-containing beta-cells. PMID- 2875912 TI - Secretion and effect of somatostatin in early stages of the diabetic syndrome in C57BL/KsJ-mdb mice. AB - In a previous study in C57BL/KsJ (mdb) mice aged 12 to 90 days, we observed alterations in the secretion of insulin and somatostatin and in the inhibitory effect of the latter upon insulin secretion. This study explores whether hormonal alterations are to be found in the very early stages of the diabetic syndrome, i.e. between ages 4 and 12 days. The results demonstrate two distinct phases in the development of the syndrome: up to age 6 days, the perifused slices of pancreata of control animals present biphasic glucose-induced patterns of insulin and somatostatin secretion, whereas the diabetic animals show a diminished first peak of insulin secretion, but a similar pattern of somatostatin secretion, to that of the control animals; between ages 7 and 12 days, the pancreata of diabetic mice exhibit insulin hypersecretion in basal conditions, and an absence of the first secretion peak and insulin hypersecretion in the second phase in response to glucose stimulation. The glucose-induced pattern of somatostatin secretion presents hormonal hypersecretion in both phases. B-cell sensitivity to the inhibitory effect of somatostatin is diminished in mdb mice of the above mentioned groups, an alteration which becomes more evident as diabetes evolves. The results show that, in very early stages of the evolution of the diabetic syndrome in C57BL/KsJ (mdb) mice, there are already alterations in insulin and somatostatin secretion patterns and in the inhibitory effect of the latter on insulin secretion. PMID- 2875913 TI - [Prognosis of patients with myocardial infarct]. PMID- 2875914 TI - [Antacids: what role in the treatment of ulcer disease?]. PMID- 2875915 TI - [Gamma-glutamyl transpeptidase serum activity: a useful but insufficient test for detecting chronic hepatopathies]. PMID- 2875916 TI - Bethanechol increases the diagnostic yield in patients with esophageal chest pain. AB - The diagnostic yield of routine esophageal manometrics in evaluating noncardiac chest pain is low. To determine if bethanechol stimulation would increase the diagnostic yield, we examined 87 patients with chest pain but no gastroesophageal reflux, 47 patients with gastroesophageal reflux but no chest pain, and 20 normal subjects. All subjects underwent standard esophageal manometrics before and after two doses of 50 micrograms/kg body wt bethanechol administered subcutaneously 15 min apart. Mean amplitude and duration of contractions and percentage of abnormal contractions were measured in the distal 7 cm of the esophageal body. Pathologic manometric parameters were defined as mean +/- 2 SD of values obtained in normal patients. Patients with chest pain had pathological responses for amplitude of contraction, duration of contraction, and percentage of abnormal contractions of 31%, 14%, and 22%, respectively, in the basal period. This increased to 43%, 66%, and 40%, respectively, after the first dose of bethanechol and to 53%, 85%, and 82% after the second dose of bethanechol. Chest pain was reproduced with new manometric abnormalities in 46% of patients after the first dose of bethanechol and in 77% after the second dose. Our conclusions are that: sequential bethanechol administration significantly increases the diagnostic yield of standard esophageal manometrics in the evaluation of noncardiac chest pain and duration of contraction after pharmacologic provocation with bethanechol is the best parameter to segregate patients with chest pain from normal subjects and gastroesophageal reflux patients. PMID- 2875917 TI - Cholinergic mediation of gamma-aminobutyric acid-induced gastrin and somatostatin release from rat antrum. AB - Addition of gamma-aminobutyric acid (GABA) to antral mucosal fragments in short term incubation results in dose-dependent and bicuculline-sensitive stimulation of gastrin release and inhibition of somatostatin release, respectively. These effects of GABA on antral gastrin and somatostatin release closely resembled the actions of cholinergic agonists on G- and D-cell function. The present study examines the possibility that the effects of GABA on antral peptide release may be mediated, in part, through stimulation of antral cholinergic neurons. Inclusion of either atropine or pirenzepine in incubation medium prevented GABA induced stimulation of gastrin release and inhibition of somatostatin release. Addition of the acetylcholinesterase inhibitor, physostigmine, caused a leftward shift in the GABA dose-response curve and increased by 10-fold the sensitivity of the antral preparation to GABA stimulation. Studies with tetrodotoxin suggest that GABA-stimulated gastrin release is mediated through activation of neurons contained within the antral mucosal/submucosal fragments. Hexamethonium, the ganglionic nicotinic receptor antagonist, did not affect GABA-induced gastrin release. These results indicate that GABA affects antral gastrin and somatostatin release through stimulation of antral postganglionic cholinergic neurons. PMID- 2875918 TI - Cholinergic modulation of the release of serotonin in the gastric interstitial fluid. An in vivo study in rabbits. AB - Dialysis fibers chronically implanted into the gastric submucosa of rabbits allowed us to simultaneously (a) collect an interstitial fluid dialysate in which 5-hydroxytryptamine concentrations were measured, and (b) locally perfuse drugs such as acetylcholine, neostigmine, and atropine, which stimulated the release of 5-hydroxytryptamine. The effect of acetylcholine was not blocked by atropine but was blocked by hexamethonium. Furthermore, 5-hydroxytryptamine concentrations in the interstitial fluid were lower when acetylcholine and hexamethonium were injected together than when hexamethonium was injected alone. We conclude that acetylcholine stimulates the release of 5-hydroxytryptamine into the gastric interstitial fluid by acting on nicotinic receptors, and has inhibitory effects by stimulating the muscarinic receptors. PMID- 2875920 TI - Effects of local anaesthetics on responses of human saphenous vein and bovine coronary artery to neurotransmitters, acetylcholine, noradrenaline and 5 hydroxytryptamine. AB - The effects of 5 different local anaesthetics, lignocaine, etidocaine, prilocaine, mepivacaine, bupivacaine, and 3 different neurotransmitters, acetylcholine (ACh), noradrenaline (NA), 5-hydroxytryptamine (5-HT) on tone and contractility of human saphenous vein and bovine coronary artery were studied and compared in vitro. The experiments were carried out to see if there were species or tissue differences in the action of local anaesthetics and neurotransmitters at vascular smooth muscle, i.e. saphenous vein and coronary artery. Another important aspect was to see if local anaesthetics modified cholinergic (ACh), adrenergic (NA) and serotoninergic (5-HT) responses in vascular smooth muscle. Among the local anaesthetics studied, lignocaine and etidocaine produced prolonged relaxations, whereas prilocaine, mepivacaine, bupivacaine produced contractions in the saphenous vein and coronary artery. High concentrations of the latter drugs produced relaxations in the blood vessels. Among the local anaesthetics, lignocaine produced differential effects on saphenous vein and coronary artery, its effect on the latter was 3 times larger than on the saphenous vein. ACh, NA and 5-HT contracted the saphenous vein. In the coronary artery, ACh and 5-HT contracted whereas NA relaxed the vessel. On a molar basis, ACh was less effective than NA in contracting the saphenous vein. 5-HT was equipotent on both the saphenous vein and coronary artery. Lignocaine reduced ACh, NA and 5-HT-induced contractions in the saphenous vein and those of ACh and 5-HT in the coronary artery, and shifted the control curves, non-competitively, to the right. The relaxation produced by NA in the coronary artery was enhanced by lignocaine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875919 TI - [Value of CA 125 in comparison to conventional tumor markers in ovarian cancer]. AB - It was the aim of this study to evaluate the clinical significance of the monoclonal test system CA 125 in comparison to 7 conventional laboratory procedures (TPA, PHI, CEA, LDH, GGT, AP, ESR) as tumour marker in ovarian cancer. Serum samples from 327 patients with histologically proven cancer of the ovary were analysed. Marker results were correlated to tumour activity as defined by the criteria of the UICC. Furthermore, in 175/327 patients who were clinically symptom-free after primary therapy, marker courses were analysed with regard to the development of recurrence. Positive rates and median values of CA 125, TPA, PHI and ESR showed significant increases with progression of the disease, whereas correlation was less clear-cut with CEA, LDH, GGT and AP. In clinically tumour free patients without evidence of recurrence during the further course, intermittent increases of PHI, ESR and especially TPA were found in 19-47%. However, such "false positive" marker courses were not seen with CA 125. Those patients who developed recurrent disease exhibited increasing CA 125 titres in 68%. The incidence of such "true positive" markers courses was less frequent with PHI, ESR and TPA. Our results indicate that CA 125 and--with limitations--TPA, PHI and ESR may be used in ovarian cancer control. When monitoring tumour-free patients, CA 125 exhibited the highest specificity and sensitivity. Using 65 U/ml as cut-off, a positive CA 125 titre indicates recurrent disease with great certainty. When employing PHI, ESR and especially TPA, however, the possibility of "false positive" increases has to be taken into account.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875921 TI - Enzymatic synthesis of a false cholinergic neurotransmitter: diethylaminoethyl acetate as a muscarinic agonist analog of acetylcholine. AB - Diethylaminoethyl acetate, an acetylcholine analog, was formed upon the incubation of diethylaminoethanol and acetyl-CoA with bovine brain choline acetyltransferase (acetyl-CoA: choline O-acetyltransferase; EC 2.3.1.6). The new product co-chromatographed with authentic diethylaminoethyl acetate on thin layer plates, and its formation was proportional to the duration of incubation and enzyme concentrations. When tested on guinea-pig ileum, diethylaminoethyl acetate was found to be an agonist with an ED50 of 1.3 X 10(-4) M, compared to an ED50 of 2.0 X 10(-7) M for acetylcholine. The contraction of guinea-pig ileum induced by diethylaminoethyl acetate was blocked by atropine. Moreover, diethylaminoethyl acetate induced a secretion of alpha-amylase from isolated pancreatic acini cells; this effect was also blocked by atropine. It is entirely possible that diethylaminoethyl acetate can be a false cholinergic transmitter generated in vivo when drugs such as aprophen or procaine are administered to animals, since either of these drugs can undergo enzymatic hydrolysis to generate diethylaminoethanol. A method for the synthesis of radioactive diethylamino [1,2 14C]ethyl acetate was also described. PMID- 2875923 TI - [Radiation hygiene: its problems and objectives in the light of the decisions of the 27th Congress of the CPSU]. PMID- 2875922 TI - Expression of a cloned 987P adhesion-antigen fimbrial determinant in Escherichia coli K-12 strain HB101. AB - The properties of three independent enterotoxigenic Escherichia coli isolates known to express 987P adhesion fimbriae in a manner subject to phase variation were examined. Phase variation could not be correlated with any major changes in the plasmid DNA content of these strains or with readily detectable changes in any other tested phenotypic markers. The 987P genetic determinant from one of these strains, E. coli 987, was cloned into the non-fimbriated E. coli K-12 strains HB101, and expressed, using the cosmid vector system. 987P fimbriae produced by cells harbouring these recombinant plasmids (987P+ phenotype) could not be distinguished from 987P fimbriae produced by strain 987. Expression of 987P fimbriae from some recombinant plasmids was unstable but none of the recombinants exhibited the phase variation phenotype displayed by the parental strain. One recombinant plasmid, pPM200, contained an insert of strain 987 DNA of ca. 33 kb. The HB101[pPM200] displayed a rather stable 987P+ phenotype, but this was not true for several hosts, since pPM200 acquired approx. 20-kb deletions following transformations of E. coli K-12 strains other than HB101. The deletions mapped to the same region of pPM200 irrespective of the host strain transformed. Cells harbouring the deleted plasmids did not express 987P fimbriae (987P- phenotype). PMID- 2875924 TI - Increased CSF levels of somatostatin in patients with brain tumours and intracranial hypertension. AB - The cerebrospinal fluid (CSF) levels of somatostatin in patients with brain tumours, communicating hydrocephalus, lumbar-disc disease (treated as a control) were measured by specific radioimmunoassay. The somatostatin concentration in the patients with brain tumours and intracranial hypertension was significantly higher compared to those with brain tumours and normal CSF pressure. CSF somatostatin content in patients with communicating hydrocephalus, was similar to patients with brain tumours and normal CSF pressure, and did not show a significant difference from the control group. The authors discuss possible reasons for such results obtained in patients with brain tumours and intracranial hypertension. PMID- 2875925 TI - Similar triiodothyronine releasing activity of thyroid stimulating antibodies in human and porcine thyroid slices. AB - In an approach to addressing species specificity of thyroid stimulating antibodies (TSAb) stimulation of T3 release by Graves' sera was comparatively studied in human and porcine thyroid slices. A high sensitivity and specificity was found for the T3 bioassay independently on the use of human or porcine thyroid. Moreover, activity indices of the individual sera in both tissues were significantly correlated to each other and to circulating hormone levels in untreated disease. In conclusion, we suppose a lack of functionally relevant differences between target antigens, brought about probably by the TSH receptor itself and other membrane components, in human and porcine thyroid. Thus, for clinically applicable T3 releasing bioassay porcine thyroid may be alternatively used. In addition, this bioassay renders the advantage of reflecting the activity of disease. PMID- 2875926 TI - Growth hormone-releasing factor: a new chapter in neuroendocrinology. AB - The isolation and characterization of growth hormone-releasing factor (GRF) has initiated a new and exciting era in our understanding of the neuroendocrine regulation of pituitary growth hormone (GH) secretion. This report briefly describes the isolation and characterization of GRF, factors which modulate the GH response to GRF and the effects of chronic administration and deprivation of GRF on somatic growth. The intent of this report is to serve as a general introduction on biochemical and physiological aspects of GRF. The following reports from this symposium will then cover many of these topics in much greater detail. PMID- 2875927 TI - Testosterone treatment of men with alcoholic cirrhosis: a double-blind study. The Copenhagen Study Group for Liver Diseases. AB - A double-blind, placebo-controlled multicenter trial was conducted to determine the efficacy of oral testosterone treatment (200 mg three times daily) in men with alcoholic cirrhosis. By skewed randomization (3:2), 134 patients received testosterone and 87 placebo. Patients were followed from 8 to 62 months (median = 28 months). In the testosterone group, 33 patients died (25%; 95% confidence limits = 18 to 33%) as compared to 18 (21%; 95% confidence limits = 13 to 31%) in the placebo group. Taking age and significant prognostic variables into consideration, this corresponds with a relative mortality risk of 1.17 (95% confidence limits = 0.65 to 2.15) in the testosterone group vs. the placebo group. Testosterone treatment did not significantly affect liver biochemistry, prevalence of complications to cirrhosis or causes of death. Patients treated with testosterone developed significantly (p less than 0.05) higher serum testosterone and blood hemoglobin concentrations and significantly (p less than 0.05) lower plasma IgM concentrations as compared to the placebo group. The prevalence of gynecomastia decreased significantly (p less than 0.05) in the testosterone group as compared to the placebo group. We conclude that oral testosterone treatment has no beneficial effect on survival and liver biochemistry in men with alcoholic cirrhosis, and adverse effects cannot be excluded. PMID- 2875928 TI - Morphological findings in the liver of children with cystic fibrosis: a light and electron microscopical study. AB - Liver tissue from five children with cystic fibrosis, obtained through percutaneous liver biopsies, have been investigated via light and electron microscopy. None of the patients had clinical evidence of liver disorder, and their blood chemistry was mainly normal. Light microscopy showed slight fibrosis in three cases, more advanced fibrosis in one case and focal cirrhotic changes in one case. All patients had fatty infiltration in the hepatocytes and glycogen in the nuclei of these cells. Electron microscopy showed an increase in the number of Ito cells around the portal tracts and also fibrosis in all patients. In the majority of hepatocytes, no evident necrosis was seen. Hypertrophy of the smooth endoplasmic reticulum and the Golgi apparatus were noted. Large lysosomes containing lipofuscin and lipids were also present. No direct evidence of cholestasis could be seen in the hepatocytes. The bile canaliculi were not dilated and did not contain bile plugs. No bile pigment was seen in the cells, and direct evidence of cholestasis was thus not found in the hepatocytes. Other organelles, such as the rough endoplasmic reticulum, peroxisomes and mitochondria, had a normal appearance. Bile ducts, even when seen in fibrotic portal tracts, were not dilated. The ultrastructural findings cannot explain the basis for the liver cell damage. Cholestasis does not seem to be a presumable etiological factor as judged from the findings in the present study. PMID- 2875929 TI - Towards a complete linkage map of the human X chromosome. AB - In the seven years since the first human gene was cloned, several hundred coding sequences and many more random single copy DNA sequences have been isolated. Many of these show restriction fragment length polymorphisms (RFLPs) and can be used as genetic markers in inheritance studies. RFLPs enable the construction of complete linkage maps of individual human chromosomes which can then be used as a mapping resource for other genes and disease loci. The isolation of chromosome specific sequences has been greatly facilitated by the purification of human chromosomes by flow cytometry. Sub-localisation of the polymorphic DNA probes along the chromosome can be achieved using in situ hybridisation or rodent/human hybrid cell lines. There are now more than one hundred DNA probes assigned to the human X chromosome and a preliminary genetic map suggests that the chromosome is at least 200 cm long. Some of these DNA sequences have been shown to be linked to disease loci such as Duchenne and Becker muscular dystrophy, X-linked mental retardation and retinitis pigmentosa. PMID- 2875930 TI - The role of the HPRT gene in human disease. AB - Human HPRT deficiency leads to two major forms of human disease. Partial enzyme deficiency results in gouty arthritis, while an almost complete deficiency leads to the Lesch-Nyhan disease. The latter is characterized by severe neurological dysfunction in addition to gouty arthritis, including retardation, choreoathetosis and aggressive and compulsive self-mutilation. The biochemical basis for the neurological symptoms is not understood. The human and mouse cDNA (RNA copy) genes have been isolated and sequenced. In addition, the amino acid sequence of the human protein has been directly determined. The human and mouse proteins differ at 7 amino acids out of the total, (including the N terminal methionine, which is processed off during maturation) of 218. There are 42 out of 654 nucleotide differences between the human and mouse genes in the amino acid coding region. The mouse genomic structure has been determined. It has 9 exons and 8 introns with a total size of approximately 36 kb. The human gene is very similar with identical intron-exon junction points and approximately the same total gene size. Both mouse and human presumed promotor region at the 5' end, lack a recognizable promotor in the form of a "TATAA" box and are very G-C rich, though not the same. This may be a feature of most "housekeeping" genes. HPRT gene point mutations in three gouty arthritis and one Lesch-Nyhan patient have been identified by peptide sequencing. Six gross gene rearrangements have been identified in Lesch-Nyhan HPRT genes. However it is likely that most mutations are point mutations or small deletions. So far all gene mutations identified are different from all others. The gene has been engineered into retrovirus vehicles which allows its efficient introduction into a wide variety of cells, including mouse marrow stem cells. This may allow treatment of Lesch-Nyhan patients as a model of gene therapy. PMID- 2875931 TI - The utilization of the human phosphoglycerate kinase gene in the investigation of X-chromosome inactivation. AB - The X-linked human Pgk gene has been cloned and partially characterized, and some preliminary results have been obtained regarding active vs. inactive gene comparisons of chromatin structure and methylation patterns. As yet we can say nothing definitive about what role, if any, these differences may play in X inactivation. The studies showing that DNA from the inactive X chromosome in mature somatic cells does not function in transformation of the Hprt gene strongly imply modification of the inactive X chromosome at the DNA level. However, methylation studies with the Hprt, Gd Pgk genes have revealed a complexity of methylation patterns including hypermethylation of parts of the active X gene. Resolution of just what difference is critical in expression, differentiating between cause and effect, and extrapolating to the spreading and initiation aspects of X inactivation are still, unfortunately, long-range goals. The Pgk system may be of special value in unraveling some of these difficult questions. A unique autosomal Pgk locus exists and should allow an informative comparison between an X-linked housekeeping gene and an autosomal, tissue specific gene encoding proteins of identical enzymatic function. The proximity of Pgk to the X-inactivation control center may be useful in identifying the starting point of this very important event in early mammalian development. PMID- 2875932 TI - Beta-globin gene disorders in Italy and the Mediterranean area. PMID- 2875933 TI - The molecular genetics of hyperlipidemia. PMID- 2875934 TI - From hemophilia B to hemophilia A via the fragile X locus: genes and recombination in the distal region of the human X chromosome long arm. PMID- 2875935 TI - Mapping of rare X-linked genes through DNA polymorphisms and identification of crossover points. PMID- 2875936 TI - Ehlers-Danlos syndrome type IV: cosegregation of the phenotype to a COL3A1 allele of type III procollagen. AB - Ehlers-Danlos syndrome (EDS) type IV is a rare and catastrophic genetic disorder of the connective tissue. Individuals from two families with this disorder were studied for a restriction fragment length polymorphism (RFLP) associated with the COL3A1 gene. Our results suggested cosegregation of the EDS type IV phenotype with a COL3A1 RFLP allele. Biochemical studies in cultured skin fibroblasts indicated the presence of different mutations affecting the stability and secretion of the pro alpha 1(III) chains of type III procollagen in the two families, thus suggesting that EDS type IV is biochemically heterogeneous. Our data demonstrated the feasibility of molecular diagnosis in this condition using COL3A1 gene related RFLPs. PMID- 2875937 TI - Attenuated activities and structural alterations of arylsulfatase A in tissues from subjects with pseudo arylsulfatase A deficiency. AB - It had been shown previously that arylsulfatase A activity was attenuated in pseudo arylsulfatase A deficiency fibroblasts and that subunits of the enzyme were smaller than subunits of the enzyme in normal fibroblasts. Attenuated enzyme activity has now been affirmed in other tissues. Subunits of the enzyme from these sources were also found to be smaller with apparent molecular size 59 and 56 kdaltons. Subunits of enzyme in corresponding control tissues were larger and there was heterogeneity in apparent molecular size as follows: fibroblasts, 63 and 59 kdaltons; liver, 63 and 59 kdaltons; kidney, 63 and 58 kdaltons; spleen, 63 and 58 kdaltons; placenta, 62 and 58 kdaltons; and urine, 61 and 57 kdaltons. Attenuated enzyme activity and structurally altered enzyme in pseudo arylsulfatase A deficiency appears to be systemic. However, the reason for reduced amounts of structurally altered enzyme with normal catalytic activity is unresolved. PMID- 2875938 TI - A Taq 1 gamma-globin DNA polymorphism: an African-specific marker. AB - The allele frequency of a Taq 1 gamma-globin gene restriction fragment length polymorphism (RFLP) is reported in ten population groups. In four African populations the 3.0 kb RFLP is common (50/132 beta A chromosomes), whereas it is completely absent in six European/Asian populations (0/277 beta A chromosomes). This Taq 1 RFLP is thus a specific African population marker. PMID- 2875939 TI - Linkage analyses of multiple endocrine neoplasia, type 2A (MEN-2A) with 20 DNA polymorphisms: 5% of the genome excluded. AB - Pairwise linkage analyses are reported between the locus for multiple endocrine neoplasia type 2A (MEN-2A) and 20 restriction fragment length polymorphisms (RFLPs) in a single large kindred which was previously screened for linkage with this form of cancer using 23 blood group and serum protein polymorphisms. No significant, positive lod scores have been obtained so far. These 20 RFLPs have excluded the MEN2 locus from about as much of the genome as did the 23 classical markers previously reported. This is a clear demonstration of the value of RFLPs for linkage studies since these 20 RFLPs were not selected for being the most polymorphic of those available. Over 10% of the human genome has been excluded from linkage with the MEN2 locus in this particular family. PMID- 2875940 TI - The rabbit immune system: cells regulating the proliferative response of purified T cells to concanavalin A and phytohaemagglutinin. AB - T cell specific, B cell specific and Ia specific polyclonal antisera, as well as monoclonal antibodies, were employed to characterize cells involved in regulation of T cells, proliferating upon stimulation with concanavalin A or phytohaemagglutinin. Evidence for Ia+ accessory cells was obtained and the constellation of membrane antigens was determined by cytotoxic cell kill with the above mentioned antibodies. Help given by Ia+ cells was not blocked by polyclonal antibody against Ia, in the absence of complement. There was indirect evidence that a fraction of helper/accessory cells were Ia-. PMID- 2875941 TI - Genetic polymorphism at the mouse immunoglobulin J kappa locus (Igk-J) as demonstrated by Southern hybridization and nucleotide sequence analysis. AB - Comparison of the nucleotide sequences of the C.C58 M75 myeloma kappa chain gene and the BALB/c germ-line J kappa segments suggested that the J kappa regions of C.C58 and BALB/c might be distinguished by restriction enzyme polymorphisms. This was shown to be the case in Southern hybridizations of Hinf I and Acc I digests of liver DNA from these and other strains with a J kappa-specific probe. Tests of a wide variety of inbred, congenic, recombinant, and recombinant-inbred strains provided evidence for three alleles, Igk-Ja, Igk-Jb, and Igk-Jc, the type strains for which are C58/J, BALB/c, and SJL/J, respectively. Analysis of the B6.PL(85NS) congenic strain suggests that the Igk-J locus lies in the neighborhood of the Lyt 2/Lyt-3 loci, approximately 0.30 cM from the V gene segment determining the Igk VSer and Igk-Efl polymorphisms. Finally, nucleotide substitutions lead to amino acid sequence differences between the C.C58 M 75 kappa gene and the BALB/c germ line in J kappa 2 and J kappa 4. Two of these substitutions reflect true germ line differences, raising the possibility that idiotype differences observed among strains could reflect J kappa as well as V kappa differences. PMID- 2875942 TI - DNA typing of HLA-DR antigens in systemic lupus erythematosus. AB - HLA-DR typing is technically difficult in systemic lupus erythematosus (SLE), where patients have low numbers of peripheral B cells, often of poor viability and weak in antigenic expression. In this series, one third of SLE patients could not be HLA-DR typed by serological techniques, highlighting the potential for systematic bias in DR antigen assignment in studies of HLA and SLE. This potential bias was examined by comparing serological DR results with DNA-DR typing, achieved by examining Taq I fragments of DR beta, DQ alpha, and DQ beta which permitted unequivocal DR phenotyping of all patients, including the 35% for whom conventional DR typing was technically impossible. This showed the success of serological DR antigen assignment was indeed nonrandom, with HLA-DR2 and -DR3 significantly more readily identifiable than DR5 and DRw13. Our study suggests that technical problems may well have contributed to conflicting reports regarding the association of DR2 or DR3 with SLE. Here, DNA-DR phenotyping showed HLA-DR3 is significantly (P less than .05) associated with an increased risk for SLE (54% in 46 patients, 36% in 134 controls) and HLA-DR2 is not. PMID- 2875943 TI - HLA-DQ polymorphism analyzed by sequential restriction endonuclease DNA digestion. AB - A direct, physical correspondence between certain Pst I-generated genomic DNA fragments and Taq I-generated fragments, revealed with HLA-DQ alpha or -DQ beta gene probes, has been demonstrated. As an immediate consequence, the nature of the DQ and DX hybridized genes contained in the fragments was established. Taq I generated DQ allelic forms which associate with serologically defined DR1, DR2, and DRw6 specificities were also proven to be sensu stricto "splits" of the Pst I generated allelic form associated with all three DR specificities. PMID- 2875944 TI - Efficacy of a slow release formulation of Bacillus thuringiensis H. 14 against mosquito larvae. PMID- 2875945 TI - Alternatives to traditional antihypertensive therapy. PMID- 2875946 TI - Role of dopamine in the inhibition of vasopressin secretion by L-dopa in carbidopa-treated dogs. AB - Elevation of brain catecholamine levels by systemic administration of L-dopa in dogs pretreated with the dopa decarboxylase inhibitor carbidopa inhibits the secretion of vasopressin and adrenocorticotropic hormone (ACTH) and decreases arterial blood pressure. The aim of the present study was to determine whether the inhibition of vasopressin secretion is mediated by dopamine or norepinephrine, both of which have been implicated in the control of vasopressin secretion, and whether the decrease in vasopressin secretion contributes to the suppression of ACTH secretion and fall in blood pressure produced by L-dopa. This was accomplished by comparing the effects of dopamine and alpha-adrenergic receptor antagonists on vasopressin, ACTH, and blood pressure responses to L dopa. The effect of a specific antagonist of the vasoconstrictor action of vasopressin also was studied. Injection of L-dopa (20 mg/kg i.v.) in dogs pretreated with carbidopa (20 mg/kg i.v.) caused reductions in plasma vasopressin concentration (from 16.0 +/- 4.8 to 3.8 +/- 0.9 pg/ml; p less than 0.05), plasma ACTH concentration (from 96.0 +/- 20.4 to 49.2 +/- 10.0 pg/ml; p less than 0.05), and mean arterial pressure (from 121 +/- 6 to 78 +/- 5 mm Hg; p less than 0.05). Pretreatment with pimozide (1 mg/kg i.p.) completely blocked the inhibition of vasopressin secretion by L-dopa but failed to block the suppression of ACTH secretion (57.6 +/- 11.8 to 34.0 +/- 5.1 pg/ml; p less than 0.05) or the decrease in mean arterial pressure (126 +/- 5 to 93 +/- 7 mm Hg; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2875947 TI - Modulation of guanylate cyclase by lipoxygenase inhibitors. AB - Drugs that inhibit endothelium-dependent relaxation were tested to determine their effect on soluble guanylate cyclase purified from dog aorta. Basal, arachidonic acid (10(-5) M)-stimulated, and nitroprusside (5 X 10(-5) M) stimulated guanylate cyclase activities were inhibited by methylene blue and the lipoxygenase inhibitors nordihydroguaiaretic acid and eicosatetraynoic acid. The effective inhibitory doses were in the range of those that have been reported to inhibit endothelium-dependent relaxation. Other compounds known to inhibit endothelium-dependent relaxation had little or no effect on guanylate cyclase activity. Basal guanylate cyclase activity was more resistant to inhibition than were activated states of the enzyme. The data suggest that reported inhibition of endothelium-dependent relaxation by some lipoxygenase inhibitors may be the result, at least in part, of their direct effect on guanylate cyclase activity. PMID- 2875948 TI - Interaction of a 60-kilodalton D-mannose-containing salivary glycoprotein with type 1 fimbriae of Escherichia coli. AB - A 60-kilodalton glycoprotein previously isolated and purified from human saliva (J. B. Babu, E. H. Beachey, D. L. Hasty, and W. A. Simpson, Infect. Immun. 51: 405-413, 1986) was found to interact with type 1 fimbriae and prevent adhesion of type 1 fimbriated Escherichia coli to animal cells in a D-mannose-sensitive manner. Purified salivary glycoprotein agglutinated type 1 fimbriated E. coli and, at subagglutinating concentrations, blocked the ability of type 1 fimbriated E. coli to attach to human buccal epithelial cells or agglutinate guinea pig erythrocytes. Both interactions were inhibited by alpha-methyl-D-mannoside but not by alpha-methyl-D-glucoside. Complexing of the glycoprotein to type 1 fimbriae was demonstrated by molecular sieve chromatography and modified Western blots. When mixed with type 1 fimbriae, the radiolabeled salivary glycoprotein coeluted with type 1 fimbriae from a column of Sepharose 4B. When blotted from a sodium dodecyl sulfate gel to nitrocellulose sheets, the glycoprotein interacted directly with type 1 fimbriae applied to the blots. Both of the latter interactions also were blocked by alpha-methyl-D-mannoside but not by alpha methyl-D-glucoside. Chemical modification of the glycoprotein with sodium metaperiodate abolished its ability to interact with isolated type 1 fimbriae or type 1 fimbriated E. coli. These results suggest that the carbohydrate moiety of the 60-kilodalton glycoprotein serves as a receptor for type 1 fimbriae in the oral cavity, and we postulate that the interaction may cause agglutination and early removal of E. coli, thereby preventing colonization by these organisms of oropharyngeal mucosae and dental tissues. PMID- 2875949 TI - Heat-modifiable envelope proteins of Bordetella pertussis. AB - Several envelope proteins of Bordetella pertussis demonstrated differences in electrophoretic mobility, depending upon solubilization temperature before sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These proteins were exposed on the cell surface as judged by their accessibility to radiolabeling with 125I. Monoclonal antibodies to two of the heat-modifiable proteins (Mrs of 18,000 and 91,000) reacted with intact cells in immunofluorescence microscopy experiments, also indicating surface exposure of these two proteins. Two-dimensional gel electrophoresis revealed that two heat-modifiable proteins (a major protein with an Mr of 38,000 and one with an Mr of 18,000) migrated as higher-Mr moieties when solubilized at low temperatures (25 degrees C). Three proteins (Mrs of 91,000, 32,000, and 30,000) and possibly a fourth (31,000) migrated as lower-Mr species when solubilized at 25 degrees C, as revealed in the two-dimensional gel system; these three proteins were found only in virulent B. pertussis and were not detected in a phase IV avirulent strain nor in a strain modulated to phenotypic avirulence by growth in nicotinic acid. The 38,000 molecular-weight protein (38K protein) and a 25K protein were found to be noncovalently associated with the underlying peptidoglycan. Small amounts of the 91K and 18K proteins were also found associated with peptidoglycan. PMID- 2875950 TI - Interactions of gonococci with HeLa cells: attachment, detachment, replication, penetration, and the role of protein II. AB - Colony variants of Neisseria gonorrhoeae differ in their interactions with eucaryotic cells. When gonococci were cultivated with HeLa cell monolayers, the opacity phenotype (Op) became increasingly dominant in the subpopulation of organisms which adhered to the HeLa cells. Once bound, Op organisms displayed very low levels of detachment. Adherent Op gonococci exhibited generation times up to threefold greater than cultures containing gonococci in the absence of HeLa cells. In addition, the progeny of adherent Op organisms remained bound to the HeLa cell monolayer. Both piliated (P+) and transparent (Tr) colony types attached to HeLa cells, but their progeny were retained less efficiently. Gonococci bound to HeLa cells were subjected to the bactericidal action of fresh rat serum and approximately 0.5 to 2.5% survived, irrespective of their opacity or piliation phenotype. Incubation with gentamicin resulted in a 10- to 50-fold further reduction in viability. Pretreatment of HeLa cell monolayers with the microfilament-disrupting agent cytochalasin b diminished gonococcal survival in either serum or gentamicin by up to eightfold. In contrast, cytochalasin b treatment did not decrease survival of the commensal organism N. sicca. The data suggest that very few gonococci are completely interiorized and a small proportion of adherent gonococci are partially protected from the soluble-phase environment by HeLa cells. PMID- 2875951 TI - Identification of the O-linked sialyloligosaccharides of glycophorin A as the erythrocyte receptors for S-fimbriated Escherichia coli. AB - The erythrocyte receptors for S-fimbriated Escherichia coli, which causes sepsis and meningitis in newborn infants, were investigated. Neuraminidase and trypsin treatments of erythrocytes abolished the hemagglutination ability of the bacteria. To identify the receptor glycoproteins, we separated erythrocyte membrane proteins by gel electrophoresis, blotted them to nitrocellulose, and incubated them with 125I-labeled bacteria. The only bacterium-binding bands identified corresponded to glycophorin A dimer and monomer, and the binding was abolished by neuraminidase treatment of the blot. Radiolabeled bacteria also bound to purified glycophorin A adsorbed to polyvinyl chloride microwells, and the binding was inhibited by other sialoglycoproteins and isolated sialyloligosaccharides containing the NeuAc alpha 2-3Gal sequence. Oligosaccharides which contain the NeuAc alpha 2-3Gal beta 1-3GalNAc and NeuAc alpha 2-3Gal beta 1-3(NeuAc alpha 2-6)GalNAc sequence and which are identical to the O-linked saccharides of glycophorin A were twofold more effective inhibitors of binding than were other oligosaccharides containing the NeuAc alpha 2-3Gal sequence. The replacement of sialic acid in asialoerythrocytes with a purified Gal beta 1-3GalNAc alpha 2-3 sialyltransferase, which forms the O-linked NeuAc alpha 2-3Gal beta 1-3GalNAc sequence in asialoglycophorins, restored bacterial hemagglutination. These results indicated that the major erythrocyte receptor for S-fimbriated E. coli is the NeuAc alpha 2-3Gal beta 1-3GalNAc sequence of the O linked oligosaccharide chains of glycophorin A. PMID- 2875953 TI - Expression of Ly-6.2 and Thy-1 antigens on NIH 3T3 cells suppressed after transformation with activated human ras-oncogenes. AB - We have studied the expression of several cell surface antigens in NIH 3T3 cells after neoplastic transformation with activated human ras and myc oncogenes. The binding of monoclonal antibodies (MAbs), specific for mouse differentiation antigens Ly-6.2, Thy-1 and 9F3, to normal and transformed cells was assessed using a fluorescence-activated cell sorter (FACS IV). Significant reduction of Ly 6.2 and Thy-1 antigen expression was detected in cells transformed with either the N-ras, Ki-ras or H-ras oncogenes but not in c-myc transfected cells. 9F3 antigen expression remained at the original high level in all transfectants studied. Normal levels of Ly-6.2 and Thy-1 expression reappeared in revertants derived from unstable ras-transfectants. These data indicate that ras sequences did not preferentially transform cells that were deficient in Ly-6.2 and Thy-1 antigens. It was also shown that the reduced binding of anti-Ly-6.2 antibodies to ras-transfectants was not due to a masking effect of increased cell-surface sialylation occurring in ras-transfected cell lines. Other possible explanations of the detected phenotypic changes are discussed. The results extend the range of tumor-associated membrane alterations in NIH 3T3 cells following transfection with human tumor DNA containing activated ras oncogenes by a hitherto unreported alteration in the expression of Ly-6 and Thy-1 antigens. PMID- 2875952 TI - Identification and characterization of a uroepithelial cell adhesin from a uropathogenic isolate of Proteus mirabilis. AB - Proteus mirabilis is a frequent cause of urinary tract infections in rehabilitation hospitals and among persons with structural abnormalities of the urinary tract. Adherence to uroepithelial tissues may be an important virulence determinant in these infections because most Proteus strains adhere to desquamated uroepithelial cells. To identify the adherence factor responsible for this phenomenon, we sheared outer membrane material from 35SO4-radiolabeled bacteria and allowed it to bind to uroepithelial cells. Following sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the major adherence element was a protein with an apparent molecular weight of 17,500 and was provisionally designated as the uroepithelial cell adhesin. This adhesin was purified by heat shock and gel filtration on Sepharose CL-4B. After purification, the adhesin was seen assembled as long, flexible rods by electron microscopy. The N-terminal amino acid sequence of the subunit had limited homology with that of the K99 fimbriae of Escherichia coli. PMID- 2875954 TI - Respiratory effects of four adrenergic blocking agents combined with a diuretic in treating hypertension with concurrent chronic obstructive lung disease. AB - The study was a comparison of the effects on respiratory function produced by four antihypertensive agents with receptor-blocking properties (atenolol, oxprenolol, labetalol, metoprolol), when used in combination with a diuretic (chlorthalidone) in four homogeneous groups of hypertensive patients also suffering from chronic obstructive lung disease. All the agents with the exception of labetalol caused systematic and considerable worsening of functional parameters monitored in the trial. Treatment with labetalol, on the other hand, led to an improvement in respiratory function. Labetalol thus proved to be the most reliable and selective of the drugs tested for administration to patients with severe chronic airflow limitation. PMID- 2875955 TI - Age-related multiple-dose pharmacokinetics and anxiolytic effects of delorazepam (chlordesmethyldiazepam). AB - The kinetics of delorazepam (chlordesmethyldiazepam; CDDZ), and its major metabolite, lorazepam (LRZ) during multiple-dose therapy have been evaluated in two groups of patients with primary or secondary anxiety. The 12 patients in group 1 were 46.8 +/- less than 13.2 years while the eight in group 2 were significantly older (69.7 +/- 7.8 years). All patients were given 0.5 mg twice daily of CDDZ for 30 days. Concentrations of CDDZ and LRZ in multiple blood samples collected during the study were determined by electron-capture gas-liquid chromatography. The degree of anxiety was evaluated from the Hamilton rating scale for anxiety (HRSA). CDDZ and LRZ accumulated in plasma but the rate of accumulation of CDDZ was slower than expected from studies in young volunteers and the half-life values were significantly related to age. Steady-state levels of glucuronated LRZ were also lower in elderly patients. Data indicate that CDDZ is more slowly eliminated and less metabolized as age increases. While pre treatment scores of HRSA were similar in the two groups, older patients improved significantly less than those of group 1 and had also an higher incidence of side effects. CDDZ levels positively correlated with improvement in group 1 but not in group 2. PMID- 2875956 TI - Conservative surgical treatment of tubal pregnancy: factors affecting future fertility. AB - The results of conservative surgical treatment of tubal pregnancy (salpingotomy in 10 cases, partial salpingectomy and anastomosis in two cases) were compared with radical treatment in seven cases. The subsequent pregnancy rate was 55% and 71% for the conservative and radical groups, respectively. There were no recurrent tubal pregnancies in either group. Prior presence of pelvic adhesions did not have an effect on fertility in these patients. The rate of multiparity was significantly higher in patients who became pregnant after the surgery than those patients who did not become pregnant. PMID- 2875957 TI - Specific IgG and IgA antibodies to Chlamydia trachomatis in infertile women. AB - IgG, IgA, and IgM antibody titers to Chlamydia trachomatis were determined in sera of 80 infertile women and 100 controls by a single antigen (L-2) immunoperoxidase assay. The infertile women included 50 with unexplained infertility and normal hysterosalpingogram (HSG) and 30 with abnormal HSG. The control sera included 50 from primiparous and 50 from multiparous women. The prevalence of C. trachomatis IgG antibody was significantly higher in infertile women with abnormal HSG as compared with infertile patients with normal HSG and controls (87% v. 20% and 10%, respectively). The geometric mean titer (GMT) of C. trachomatis IgG antibodies of infertile women with abnormal HSG was significantly higher than those of controls (20.7 v. 5.6). A significantly higher prevalence of C. trachomatis IgA antibodies was found in infertile women with both abnormal and normal HSG than in controls (77% and 14% v. 3% respectively). No C. trachomatis IgM antibodies (less than 2) were found in any of the infertile or control groups. The possibility that serum C. trachomatis IgA antibodies may serve as a marker for early recognition of persistent C. trachomatis is discussed. PMID- 2875958 TI - Pulmonary embolism during clomiphene therapy for infertility in a male: a case report. PMID- 2875960 TI - Prolactin in human cervical mucus. AB - The pattern of change in the levels of prolactin (PRL) in cervical mucus was studied in 19 normal ovulatory women. The concentration of PRL in cervical mucus was generally higher than that in plasma except at midcycle, when a reverse relationship was observed. The concentration of PRL in mucus obtained at midcycle was lower than mucus obtained during follicular phase or luteal phase. There were no significant differences in the total PRL content among preovulatory, midcycle and postovulatory cervical mucus samples. The amount of cervical mucus markedly increased during the periovulatory period (two days from the peak of plasma luteinizing hormone). The cervical mucus PRL level undergoes cyclic changes during the normal menstrual cycle, and the decrease in PRL concentration in mucus at midcycle is most likely a result of the dilutional effect of increased mucus volume. The physiological implication of the presence of PRL in human cervical mucus is also discussed. PMID- 2875959 TI - Andrological parameters in patients with varicocele and fertility disorders treated by high ligation of the left spermatic vein. AB - The results of surgical treatment of 50 subfertile patients with left varicocele are presented. Improvement of the spermiogram was noted as follows: 70% of patients had improvement of semen count, 48% of semen motility and 69.4% in the morphological pattern of spermatozoa. Pregnancy occurred in 50% of patients' wives. Eighty-four percent of the pregnancies took place during the first 12 months after the operation. A direct correlation was observed between the size of the varicocele and the number of pregnancies. Severely oligozoospermic patients with sperm count less than 10 million per milliliter semen constituted 72% of the men whose wives became pregnant. There was no statistically significant change after the operation in levels in the semen of luteinizing hormone, follicle stimulating hormone, testosterone and prolactin. PMID- 2875961 TI - Detection of antisperm antibodies: a cytotoxicity immobilization test. AB - The sera of 110 couples with unexplained infertility were examined for anti-sperm immobilizing antibodies with the aid of multiple-exposure photography. The sera of 10 females and 3 males had immobilizing activity. Eleven pregnancies occurred in 10 female patients in the group without immobilizing antibodies. None of the 13 females in the couples with immobilizing activity conceived. A negative correlation was found between the occurrence of serum immobilizing antibodies and incidence of pregnancy. No such correlation could be found between the occurrence of autoagglutination in the male's ejaculate and the female partner conceiving. In light of detection of anti-sperm antibodies in a patient with habitual abortions, a possible immune mechanism is suggested. PMID- 2875962 TI - Shared HLA antigens between parents and recurrent spontaneous abortion. AB - Ten couples with a history of at least three (mean 3.8) consecutive spontaneous abortions of unknown etiology and 57 normal fertile couples (means 2.6 children) were tested for HLA antigens. The frequencies of shared HLA-A, -B and -DR antigens among members of the couples were similar in both groups. Our results, as well as analysis of the data in the literature, contradict HLA antigens sharing between parents as a determinant of recurrent spontaneous abortion. PMID- 2875964 TI - Does sperm motility reflect the potential penetrating capacity? AB - This study was conducted to determine whether spermatozoal motility in the fresh ejaculate and that after various treatments correlates with the results of in vitro penetration (IVP) of zona-free hamster oocytes. In 24 different ejaculates, a poor correlation was noted between the IVP results and initial sperm motility. However, a significant (P less than .05) correlation was observed between motility of washed (0.47), incubated (0.43) and oocyte-exposed (0.41) sperm v. IVP results. Furthermore, variable proportions of motile sperm in individual ejaculates (n = 4), obtained by addition of known amounts of killed immotile sperm to fresh ejaculate, had a significantly (P less than .05) higher correlation (0.83) with IVP results. PMID- 2875963 TI - The regional distribution of NPY-, PHM-, and VIP-containing nerves in the human female genital tract. AB - The regional distributions of neuropeptide Y (NPY), peptide histidine-methionine (PHM), and vasoactive intestinal polypeptide (VIP) immunoreactivities in the human female genital tract have been estimated by specific radioimmunoassays, and their molecular forms determined by chromatography. The localisation and distribution of these three peptides was carried out by immunocytochemistry. The vagina and cervix contain high concentrations of NPY- and VIP-immunoreactive nerves, mainly localised around the vascular and nonvascular smooth muscle. VIP containing nerves were, in addition, seen beneath the cervical and, in particular, the vaginal epithelium. A comparatively high level of immunoreactive NPY is found in the fallopian tube, mainly around the circular muscle coat. There is evidence that VIP is a neurotransmitter in the female genital tract, and these results suggest a similar role for NPY and PHM. PMID- 2875965 TI - Hyaluronidase activity in split human semen. AB - Hyaluronidase is an acrosomal enzyme which participates in the dissolution of the cumulus oophorus matrix, containing hyaluronic acid, and is essential for the fertilization process. In this study hyaluronidase activity was determined in two fractions of split normozoospermic and oligozoospermic human semen. The method consisted of measurements of areas of digestion of hyaluronic acid in agar (Petri dishes) as compared to activity obtained by commercial testicular hyaluronidase. It was found that the first splits of semen, which are generally characterized by higher sperm density and better quality of sperm, exhibit higher enzyme activity (136.0 +/- 11.6-207.0 +/- 15.1 micrograms/mL) as compared to the second splits (117.8 +/- 10-134.0 +/- 12.9 micrograms/mL). PMID- 2875966 TI - Effect of stress on semen quality in semen donors. AB - Fifty-three donors with good semen quality were studied monthly for sperm count and motility over 9 to 22 months. Medical students (n = 31) in freshman and sophomore years subjected to the stress of twice-yearly examinations were compared with nonstudents (n = 22) not exposed to common stressful periods. Sperm count and quality (count X motility) for the student group were significantly elevated during examination months versus nonexamination months. Controls demonstrated no differences over these months. Differences between individuals, donor selection factors, and the effects of variable degrees of stress on sperm transport may have contributed to this finding. PMID- 2875967 TI - Effects of vitamin C deficiency on physiology of male reproductive organs of guinea pigs. AB - Vitamin C dietary deficiency in guinea pigs markedly affected the androgen sensitive parameters of the reproductive tissues--testis, epididymis, vas deferens, and accessory sex glands--and caused an "androgen-deprived effect" in these target organs. This in turn altered their internal milieu and caused changes in their metal ion profile and the morphology, motility, and density of spermatozoa in the cauda epididymis and vas deferens. The sensitivity of the vas deferens to adrenaline was also reduced in scorbutic guinea pigs, thus decreasing their fertility rate. The primary action seems to be at the level of the testis, and androgen deprivation and partial antifertility effects are probably secondary manifestations consequent to the primary effect. The present study demonstrated that ascorbic acid is essential for maintaining the physiological integrity of the androgen target reproductive organs in guinea pigs. PMID- 2875969 TI - Synthesis and conformational study of two L-prolyl-L-leucyl-glycinamide analogues with a reduced peptide bond. AB - The peptide bond between Pro-Leu or Leu-Gly in Pro-Leu-Gly-NH2 was replaced by a CH2-NH function. The 1H and 13C n.m.r. studies demonstrated that HCl X Pro-Leu psi (CH2-NH)Gly-NH2 10 adopted a conformation in DMSO that is similar to the previously postulated beta-turn for the natural hormone. This was not the case for the other analogue. In vivo tests on 10 revealed an activity approximately equal to the natural compound and an increased toxicity. PMID- 2875968 TI - Effects of passive immunization against estradiol on rabbit ovum transport. AB - The role played by estradiol in control of ovum transport was studied in rabbits that were induced to ovulate by hCG stimulation. Withholding estrogen from target tissues during ovum transport by passive immunization with sheep anti-estradiol immunoglobulin (AE) resulted in accelerated oviductal transport and expulsion of ova from the uterus. The degree of accelerated transport was dependent on the duration of AE treatment. When AE treatment was started 24 h before hCG, fewer ova were recovered from the reproductive tracts at 72 h after hCG than were recovered from tracts of animals treated with a nonspecific immunoglobulin; the location of ova at 48 h after hCG was unaltered by this AE regimen. When AE treatment was started 72 h before hCG, fewer ova remained in the oviducts than were found in the tubes of controls at 48 h after hCG; and at 48 h after hCG, ova were found in the uteri of animals that had been treated with AE starting 72 h before hCG. When AE treatment was started 48 h before hCG, the position of eggs within the reproductive tract was not different from controls at 48 h after hCG. These observations support the concept that estrogen withdrawal is involved in the transport of ova through the oviduct of the rabbit, and suggest that the lack of estrogen secretion from the time of ovulation through the transport period is important in the control of normal ovum transport. PMID- 2875970 TI - 13C n.m.r. study of the structure and the metal ion binding sites of neuropeptides composed of L-Asp and L-Glu. AB - 13C NMR spectral data are presented for a variety of possible neuropeptides composed of L-Asp, Ac-L-Asp, and L-Glu which contain alpha and beta peptide linkages. The data for the various compounds are compared to the data presented for Ac-Asp-Glu, a known neuropeptide, in order to gain structural information about the related compounds. Indications are that for compounds 1 and 5, the cis peptide bond configuration exists due to the interaction of zwitterionic species. This interaction appears to be eliminated when the beta peptide bonds are formed, as in the case of compounds 3 and 7. Spin-lattice relaxation times were used to confirm the structures. Electron-nuclear relaxation rates are also used to elucidate the metal ion binding sites of these species. PMID- 2875972 TI - The organic etiology of infantile autism: a critical review of the literature. AB - Various theories have been provided in the literature regarding the etiology of infantile autism. It seems that the biological causation dominates the thinking of mental health practitioners and researchers irrespective of discipline. Areas of research include the following: neuropathological studies of the brain, autopsies, electroencephalograms, epileptic seizures, brain lateralization, studies in asymmetry; neurochemistry; genetics; and pre-, peri- and postnatal factors. A critical analysis of these studies has indicated that the evidence of organic factors tends to be rather weak and furthermore has been found to be contradictory. It is felt that the major problem lies in the fact that a large number of investigators include in their sampling children with various mental and physical disabilities and label them autistic. In general, there seems to be little information regarding the selection and little background information is offered on these children. It is suggested that a standardized and world wide diagnostic system be constructed which will provide objective etiological results. PMID- 2875971 TI - Systemic analysis of anticipating reactions. AB - A capacity for anticipating reactions realizes itself in the course of systemic activity formation, events. There is no doubt that probability of prediction proves to be possible on the basis of formation in brain structures of certain systems of anticipating excitations. Dynamics of EP analogues is an objective criterion of evaluation of the anticipating reaction central mechanisms. The term "EP analogue" conveys the phenomenon of reproduction of the EP configurations in intersignal spans. On the basis of analysis of EP analogue dynamics, we succeeded in following the process of brain structure organization into the anticipating intercentral integrations and also in elucidating the role that different afferentation redistributions play in this process by their functional significance. PMID- 2875973 TI - [When is a patient with coronary heart disease optimally treated?]. PMID- 2875974 TI - [Superfluous diagnosis? Status of muscle biopsy of collagenoses]. PMID- 2875975 TI - Conjunctival eosinophil infiltration evoked by histamine and immediate hypersensitivity. Modification by H1- and H2-receptor blockade. AB - The present histological studies have demonstrated that histamine causes dose dependent eosinophil infiltration into the conjunctiva. A highly directional movement toward the conjunctival epithelium was observed, and the presence of large numbers of degranulating eosinophils appeared to result in epithelial cell damage and goblet cell discharge. Blockade of H2-receptors by systemic cimetidine pretreatment significantly inhibited the eosinophil infiltration elicited by an intermediate histamine dose, whereas the H1-receptor blockade produced by systemic pyrilamine pretreatment markedly reduced the response to all histamine doses. The pyrilamine-insensitive residual eosinophil infiltrate was not affected by administering a cimetidine-pyrilamine combination. In animals presensitized to ovalbumin, antigen challenge evoked extensive and directional emigration of eosinophils toward the conjunctival epithelium with resultant exfoliation and depletion of goblet cell populations. In conjunctival immediate hypersensitivity, neither cimetidine nor pyrilamine alone produced an inhibitory effect, but a cimetidine-pyrilamine combination caused a significant reduction in the number of infiltrating eosinophils and prevented epithelial damage and goblet cell depletion. These results suggest that histamine may participate in the recruitment of eosinophils during immediate hypersensitivity reactions. The differential effect of pyrilamine on the eosinophil infiltration evoked by histamine or immediate hypersensitivity may, perhaps, reflect the importance of increased microvascular permeability in facilitating eosinophil emigration. PMID- 2875977 TI - A deletion mutant defines DQ beta variants with DR4 positive DQw3 positive haplotypes. AB - We describe the production of an HLA deletion mutation by radiation mutagenesis of a DR4- and DQw3-homozygous, Dw4- and Dw14-heterozygous cell line designed to analyze polymorphisms associated with DR4 and DQw3. Southern blot analysis confirms a deletion of class I and class II genes on one haplotype. Variation in DQ beta alleles associated with DQw3 was previously described by characteristic RFLP patterns for a DQ beta bene. One pattern, which correlated precisely with A 10-83 monoclonal antibody reactivity (TA10), defined an allele which we call DQ"3.1". The mutant cell line has lost the polymorphic bands on Southern blots corresponding to the DQ"3.1" allele, while the intact Dw14 haplotype retains the alternate allele at DQ beta which is DQw-3 positive. TA10-negative. These data demonstrate the segregation of two DQw3 positive DQ beta allelic variants, both associated with DR4, which can be distinguished on the basis of both RFLP and monoclonal antibody reactivity. PMID- 2875978 TI - Cryopreservation of human spermatozoa. PMID- 2875976 TI - Generation of drug metabolite antigenicity in the intestinal mucosa. AB - Both nitroreductase and transglutaminase activities have been assayed in the 10,000 X g supernatant fluids of rat intestine homogenates after Triton X-100 treatment. Incubation of 14C-nitrofurantoin in the intestine extract yielded protein-bound 14C-labeled products. Injection into rabbits of the conjugated protein similarly prepared with unlabeled nitrofurantoin elicited formation of antibodies against nitrofurantoin. These results suggest that intestinal metabolism and conjugation to protein of orally administered drugs may serve as a probable mechanism of drug allergy, and this may be accomplished by enzymatic coupling of relatively stable drug metabolites to protein carriers. PMID- 2875979 TI - Streptococcus pneumoniae cellulitis. PMID- 2875980 TI - A unique residency in general surgery. PMID- 2875981 TI - A country doctor of adventuresome spirit. Charles Ellet Lippincott. PMID- 2875982 TI - Four adults with Ebstein's anomaly. PMID- 2875983 TI - Revolution comes slowly to the law. 1. PMID- 2875984 TI - New perspectives in cardiology: pharmacodynamic classification of antiarrhythmic drugs. AB - Recent advancements in cardiac pharmacology and physiology have led to the identification of many new antiarrhythmic drugs and a better understanding of basic arrhythmogenic mechanisms. These parallel developments prompted a new nomenclature system for classifying the clinically important antiarrhythmic drugs according to their predominant electrophysiologic actions in cardiac cells. Antiarrhythmic drugs are now grouped into 4 main classes: classes I through IV. Class I agents comprise the standard membrane-stabilizing drugs such as lidocaine, quinidine, and procainamide; newer class I agents include disopyramide, aprindine, tocainide, and flecainide. Class II agents decrease sympathoadrenal excitation of the heart, and the clinically relevant members of this type act through blockade of the cardiac beta 1-adrenergic receptors; propranolol is the prototype. Class III agents selectively prolong the cardiac action potential and refractory period, and bretylium and amiodarone represent this group. Class IV agents are the calcium entry blocking drugs such as verapamil. An understanding of this classification system is essential to the internist and cardiologist who are beset with an emerging array of new antiarrhythmic drugs and affiliated pharmacodynamic terminologies. PMID- 2875985 TI - New perspectives in cardiology: recent advances in antiarrhythmic drug therapy. AB - During the past decade, advances in basic and applied cardiology have led to the introduction of several new antiarrhythmic drugs that have distinct clinical advantages over their older counterparts. These therapeutic advantages comprise either a more favorable pharmacokinetic disposition in the patient or new and perhaps novel mechanisms of antiarrhythmic actions. The class IV agent verapamil, for example, selectively blocks the slow inward Ca++ current in excitable tissues and this action is proving to be quite effective in controlling supraventricular tachyarrhythmias. Tocainide is a newly approved class I agent that exerts lidocaine-like effectiveness in treating serious ventricular arrhythmias. Unlike lidocaine, however, tocainide is not restricted to intensive care because it is effective after oral administration and has comparatively longer duration of antiarrhythmic action. Other recently approved or investigational agents include bretylium and amiodarone (class III), and aprindine, mexiletine, and disopyramide (class I). Along with clinical advantages, however, each drug has a characteristic pharmacologic-toxicologic profile and resulting spectrum of therapeutic application for only particular cardiac dysrhythmias. The advantages and disadvantages of each compound should be weighed equally when the new antiarrhythmic drugs are assessed as therapeutic alternatives for the older ones. PMID- 2875986 TI - Clostridium perfringens type C enterotoxemia in a newborn foal. AB - A 1-day old, full-term foal with a history of colic died 2 hours after admission. Necropsy revealed an extremely flaccid, fluid-filled intestinal tract. Histopathologically, the superficial intestinal mucosa was completely necrotic, with minimal inflammatory response. Numerous large, gram-positive rods covered the villi. Clostridium perfringens was isolated on bacteriologic culturing of the intestinal tract contents and was identified as type C by toxin neutralization tests. PMID- 2875987 TI - Production of hypoprothrombinaemia by cefazolin and 2-methyl-1,3,4-thiadiazole-5 thiol in the rat. AB - Recent findings have suggested that the 1-methyltetrazole-5-thiol (MTT) group contained in several beta-lactam antibiotics may be responsible for the hypoprothrombinaemia associated with these drugs. In order to determine if the hypoprothrombinaemia associated with cefazolin is due to the presence of the structurally related 2-methyl-1,3,4,-thiadiazole-5-thiol (MTD) group which it possesses, the ability of MTD and cefazolin to produce hypoprothrombinaemia in rats was examined. Female rats maintained on a vitamin K-deficient diet for ten days developed hypoprothrombinaemia after the intravenous administration of cefazolin for two subsequent days. Hypoprothrombinaemia was also produced by the oral administration to vitamin K-deficient rats of either cefazolin or MTD, while the oral administration of cefotaxime, which does not contain a thiol group, had no effect. In a rat liver microsomal system, MTD was found to be a much more potent inhibitor than cefazolin of the vitamin K-dependent step in clotting factor synthesis, the gamma-carboxylation of glutamic acid. These results suggest that the hypoprothrombinaemia associated with cefazolin may be due to the MTD group. PMID- 2875988 TI - Profile of circulating and urinary neurotransmitters in bronchial asthma. PMID- 2875989 TI - Large, unstable inserts in the chromosome affect virulence properties of uropathogenic Escherichia coli O6 strain 536. AB - The hemolytic, uropathogenic Escherichia coli 536 (O6:K15:H31) contains two inserts in its chromosome (insert I and insert II), both of which carried hly genes, were rather unstable, and were deleted spontaneously with a frequency of 10(-3) to 10(-4). These inserts were not found in the chromosome of two nonhemolytic E. coli strains, whereas the chromosomal sequences adjacent to these inserts appeared to be again homologous in the uropathogenic and two other E. coli strains. Insert I was 75 kilobases in size and was flanked at both ends by 16 base pairs (bp) (TTCGACTCCTGTGATC) which were arranged in direct orientation. For insert I it was demonstrated that deletion occurred by recombination between the two 16-bp flanking sequences, since mutants lacking this insert still carried a single copy of the 16-bp sequence in the chromosome. Both inserts contained a functional hemolysin determinant. However, the loss of the inserts not only affected the hemolytic phenotype but led to a considerable reduction in serum resistance and the loss of mannose-resistant hemagglutination, caused by the presence of S-type fimbriae (sfa). It is shown that the Sfa-negative phenotype is due to a block in transcription of the sfa genes. Mutants of strain 536 which lacked both inserts were entirely avirulent when tested in several animal model systems. PMID- 2875991 TI - Fatty acid degradation in Caulobacter crescentus. AB - Fatty acid degradation was investigated in Caulobacter crescentus, a bacterium that exhibits membrane-mediated differentiation events. Two strains of C. crescentus were shown to utilize oleic acid as sole carbon source. Five enzymes of the fatty acid beta-oxidation pathway, acyl-coenzyme A (CoA) synthase, crotonase, thiolase, beta-hydroxyacyl-CoA dehydrogenase, and acyl-CoA dehydrogenase, were identified. The activities of these enzymes were significantly higher in C. crescentus than the fully induced levels observed in Escherichia coli. Growth in glucose or glucose plus oleic acid decreased fatty acid uptake and lowered the specific activity of the enzymes involved in beta oxidation by 2- to 3-fold, in contrast to the 50-fold glucose repression found in E. coli. The mild glucose repression of the acyl-CoA synthase was reversed by exogenous dibutyryl cyclic AMP. Acyl-CoA synthase activity was shown to be the same in oleic acid-grown cells and in cells grown in the presence of succinate, a carbon source not affected by catabolite repression. Thus, fatty acid degradation by the beta-oxidation pathway is constitutive in C. crescentus and is only mildly affected by growth in the presence of glucose. Tn5 insertion mutants unable to form colonies when oleic acid was the sole carbon source were isolated. However, these mutants efficiently transported fatty acids and had beta-oxidation enzyme levels comparable with that of the wild type. Our inability to obtain fatty acid degradation mutants after a wide search, coupled with the high constitutive levels of the beta-oxidation enzymes, suggest that fatty acid turnover, as has proven to be the case fatty acid biosynthesis, might play an essential role in membrane biogenesis and cell cycle events in C. crescentus. PMID- 2875992 TI - The regulation of somatostatin production in human medullary thyroid carcinoma cells by dexamethasone. AB - There have been few studies of physiological importance on the regulation of somatostatin by hormones. We have studied the effect of the synthetic glucocorticoid dexamethasone on somatostatin production in the human medullary thyroid carcinoma TT cell line, a model for somatostatin production by the parafollicular cell. Dexamethasone inhibited somatostatin production in a dose related manner with a maximal effect at a concentration of 10(-6) M. TT cells treated with dexamethasone (10(-6) M) showed an almost complete inhibition of somatostatin peptide production by 48 h of treatment. Molecular sizing chromatography demonstrated a decrease in both the probable somatostatin precursor (13,000 dalton) and the fully processed peptide. Analysis of mRNA content by hybridization revealed that dexamethasone also caused a decrease in detectable somatostatin mRNA. The hybridizable somatostatin mRNA decreased to approximately 50% of basal levels within 12 h of treatment. Northern blot hybridization showed a decrease in a single RNA species representing mature somatostatin mRNA. Dose-response experiments revealed inhibition of both peptide and mRNA at concentrations from 1 X 10(-8) to 1 X 10(-5) M dexamethasone. Four days after withdrawal from dexamethasone treatment, peptide and mRNA levels were higher than dexamethasone-treated controls. The sex steroid estradiol had no inhibitory effect on somatostatin production. These results suggest a potential regulator of somatostatin production and provide a system for the study of somatostatin gene regulation. PMID- 2875990 TI - Purification and characterization of fimbriae from Salmonella enteritidis. AB - A human isolate of Salmonella enteritidis which displayed strong pellicle formation during static broth culture and mannose-sensitive hemagglutination produced fimbriae which were morphologically indistinguishable from type 1 fimbriae of members of the family Enterobacteriaceae. Fimbrin was purified to homogeneity, and the apparent molecular weight (Mr, 14,400) was markedly lower than that reported for the type 1 fimbrin of Salmonella typhimurium (Mr, 22,100). This fimbrin contained 40% hydrophobic amino acids and lacked cysteine. The sequence of the N-terminal 64 amino acids was determined, and sequence alignment revealed that although the 18 N-terminal residues of the S. enteritidis molecule shared considerable homology with Escherichia coli and S. typhimurium type 1 fimbrins, the S. enteritidis fimbrin lacked a 6- to 9-residue terminal sequence present in the other type 1 fimbrins and, after residue 18, shared little homology with the E. coli sequence. Antibodies raised to the purified S. enteritidis fimbrin bound to surface-exposed conformational epitopes on the native fimbriae and displayed pronounced serospecificity. These antibodies were used in the isolation of a nonfimbriated Tn10 insertion mutant which was unable to hemagglutinate. PMID- 2875994 TI - Cytotoxicity of S-(1,2-dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-L cysteine in isolated rat kidney cells. AB - S-(1,2-Dichlorovinyl)glutathione (DCVG) and S-(1,2-dichlorovinyl)-L-cysteine (DCVC) produced time- and concentration-dependent cell death in isolated rat kidney proximal tubular cells. AT-125 blocked and glycylglycine potentiated DCVG toxicity, indicating that metabolism by gamma-glutamyltransferase is required. S (1,2-Dichlorovinyl)-L-cysteinylglycine, a putative metabolite of DCVG, also produced cell death, which was prevented by 1,10-phenanthroline, phenylalanylglycine, and aminooxyacetic acid, inhibitors of aminopeptidase M, cysteinylglycine dipeptidase, and cysteine conjugate beta-lyase, respectively. Aminooxyacetic acid and probenecid protected against DCVC toxicity, indicating a role for metabolism by cysteine conjugate beta-lyase and organic anion transport, respectively. DCVC produced a small decrease in cellular glutathione concentrations and did not change cellular glutathione disulfide concentrations or initiate lipid peroxidation. DCVC caused a large decrease in cellular glutamate and ATP concentrations with a parallel decrease in the total adenine nucleotide pool; these changes were partially prevented by aminooxyacetic acid. Both DCVG and DCVC inhibited succinate-dependent oxygen consumption, but DCVC had no effect when glutamate + malate or ascorbate + N,N,N',N'-tetramethyl-p phenylenediamine were the electron donors. DCVC inhibited mitochondrial, but not microsomal, Ca2+ sequestration. These alterations in mitochondrial function were partially prevented by inhibition of DCVG and DCVC metabolism and were strongly correlated with decreases in cell viability, indicating that mitochondria may be the primary targets of nephrotoxic cysteine S-conjugates. PMID- 2875993 TI - Light-induced increases in cGMP metabolic flux correspond with electrical responses of photoreceptors. AB - The metabolism of photoreceptor cGMP and the relationship of its light-sensitive regulation to rhodopsin photoisomerization and to the photoreceptor electrical response was examined in isolated, intact rabbit retinas. The dynamics of cGMP metabolism were assessed by measuring the rate of 18O incorporation from 18O water into the alpha-phosphoryls of the guanine nucleotides. The photoreceptor electrical response was determined by measuring the aspartate-isolated mass receptor potential. Basal cGMP flux in dark-adapted retinas was 33 pmol cGMP X mg protein-1 X s-1 which translates into a metabolic rate in the rod outer segment (ROS) of 1.7 mM/min in ATP equivalents. Photic stimulation increased this flux as much as 4.5-fold. With continuous illumination, increasing intensity caused increments in cGMP metabolic flux to a maximum of 4.5-fold, with corresponding increases in the electrical response over the same 3-log unit intensity range. Tight coupling between activation of guanylate cyclase and phosphodiesterase was indicated by either no changes in cGMP steady state concentrations or relatively small fluctuations represented by increases of 50% at lower light intensities and a 12% decrease at one of the highest intensities. A stoichiometry of about 10,000 molecules of cGMP generated and hydrolyzed per photon absorbed was calculated for the lowest light intensity when the increment in cGMP metabolic flux per photon was maximal. Flashing light caused an increase in flux in proportion to frequency up to 1 Hz and a nearly proportional increase in the voltage time integral of the electrical response up to 0.5 Hz. This indicates that the temporal resolution, or "on"/"off" rate, of the cGMP metabolic response was as fast or faster than the temporal resolution of the electrical response. The concentration of cGMP remained relatively stable in spite of the marked acceleration of cGMP flux that occurred over the 32-fold range of frequencies tested. Taken together these results show that the light-accelerated rate of cGMP synthesis tightly coupled to hydrolysis becomes a primary energy-utilizing system in the photoreceptor and represents a response that fulfills certain of the fundamental criteria required of a metabolic event playing an essential role in phototransduction. PMID- 2875995 TI - Effects of permeant buffers on the initiation of photosynchronous phosphorylation and postillumination phosphorylation in chloroplasts. AB - Under canonical chemiosmotic formulations, the development of a delocalized transmembrane proton gradient should precede and, in the absence of a membrane potential, should account for all the capacity of an energy transducing system to synthesize ATP. Furthermore, any agents, such as permeant proton-absorbing buffers, that slow down the kinetics of the development of this gradient should, consequently, delay ATP synthesis. We have studied the very early (0 through 1000 ms) steps of photosynthetic ATP synthesis utilizing real-time, rapid flow-quench techniques. We have investigated the effect(s) that permeant buffers exert on this process where these buffers show no uncoupling effects, and the transmembrane potential has been collapsed by valinomycin and K+. Experimentally this system was dissected into two ATP synthesizing components, as follows: synthesis of ATP strictly concomitant with light influx and unaffected by the addition of permeant buffers. We refer to this as photosynchronous phosphorylation and synthesis of ATP monitored after the light was extinguished and which was greatly diminished by the addition of proton-absorbing permeant buffers, thus exhibiting the characteristics of conventional postillumination phosphorylation, and we suggest that it represents part of capacitance phosphorylation. The potential for capacitance phosphorylation initiates very rapidly under light and gradually builds up to steady-state level, and it is governed by canonical chemiosmotic principles. We estimate that its contribution to overall ATP yield is minimal during the first few cycles of the system and that it increases gradually towards steady state when it contributes to the majority of ATP synthesized. Neither a delocalized transmembrane proton gradient nor a strictly localized intramembrane proton pathway can account for these observations so we have proposed that a gating mechanism exists which delivers intramembrane protons initially directly to the ATP synthetase complex but subsequently to the lumen as well, and thus, allows the lumen to act as a capacitor during the steady state. This study can reconcile the findings of Ort et al. (Ort, D. R., Dilley, R. A., and Good, N. E. (1976) Biochim. Biophys. Acta 449, 108-124) with the contrasting findings of Vinkler et al. (Vinkler, C., Avron, M., and Boyer, P. D. (1980) J. Biol. Chem. 255, 2263-2266) through the opposite effects which osmotic strength and KCl concentration exert on the two ATP synthetic phases (during and after illumination) of the rapid flash technique used in those studies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2875996 TI - The antiproliferative effect of type beta transforming growth factor occurs at a level distal from receptors for growth-activating factors. AB - Transforming growth factor-beta (TGF beta) from human platelets blocks the ability of Mv1Lu mink lung epithelial cells to grow in response to serum mitogens, epidermal growth factor (EGF), or insulin. The phenotypic response of Mv1Lu cells to TGF beta is characterized by a flat, very enlarged cell morphology and a markedly increased production and accumulation of extracellular matrix fibronectin. The ability of TGF beta to alter the ligand binding or signal transducing activity of mitogen receptors in Mv1Lu cells has been examined. In contrast to NRK-49F rat fibroblasts, Mv1Lu cells do not respond to TGF beta with a decrease in the affinity or a change in the number of cell surface receptors for EGF. Soluble extracts from Mv1Lu cells contain a protein kinase activity which selectively phosphorylates ribosomal protein S6; this S6 kinase activity is elevated severalfold minutes after exposure of cells to mitogens. This kinase activity has been used as the parameter to measure the signaling ability of EGF receptors and insulin receptors in cells treated with TGF beta. We find that TGF beta does not alter the basal level of S6 kinase activity or its elevation by EGF or insulin. In TGF beta-treated cells rendered insensitive to the growth promoting action of EGF, the parameters of elevation of S6 kinase activity by EGF are similar to those of control, growth-competent cells. The results suggest that TGF beta inhibits cell proliferation by acting at a level distal from the receptors for growth-activating factors. PMID- 2875997 TI - Association of a solubilized prostaglandin E2 receptor from renal medulla with a pertussis toxin-reactive guanine nucleotide regulatory protein. AB - Prostaglandin E2 (PGE2) was found to bind specifically, reversibly, and in a protein-dependent manner to a single class of high affinity (KD approximately equal to 20 nM) binding sites in membranes prepared from canine renal outer medulla. PGE2 binding activity was solubilized from these membranes in a stable form (t1/2 greater than 14 days) in the absence of ligand in 75% yields using digitonin. The characteristics of PGE2 binding to membranes and solubilized protein were similar with respect to pH dependence, KD for PGE2, and order of potency of prostaglandins (PGE2 approximately PGE1 greater than PGF2 alpha greater than PGD2) in inhibiting the binding of [3H]PGE2. Importantly, the extents of binding of PGE2 to membranes and to a solubilized preparation partially purified by chromatography on wheat germ agglutinin-Affi-Gel 10 were both increased about 2-fold by GDP and GTP and its analogs. Treatment of the digitonin-solubilized PGE2 binding activity with 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS) rendered the binding activity insensitive to stimulation by GTP and decreased the apparent molecular weight of the peak of PGE2 binding activity from about 175,000 to about 65,000. These results suggest that the PGE2 binding activity resides in a protein which is tightly associated with, but distinct from, a guanine nucleotide regulatory (N) protein. PGE2 (greater than or equal to 10 nM) was found to stimulate GTPase activity of renal outer medullary membranes, and this stimulation was eliminated by pretreatment of membranes with pertussis toxin and NAD, but not cholera toxin and NAD. Treatment of both particulate and solubilized preparations of PGE2 binding activity with pertussis toxin plus NAD also eliminated the ability of GTP to stimulate PGE2 binding. This evidence indicates that it is the inhibitory guanine nucleotide regulatory protein, Ni, with which the PGE2 binding activity is associated. Thus, this PGE2 binding activity is an inhibitory PGE2 receptor, quite possibly one that mediates inhibition of vasopressin-induced cAMP formation in the medullary thick ascending limb and/or collecting tubule of the kidney. PMID- 2875998 TI - Chlorophyll biosynthesis in Chlamydomonas starts with the formation of glutamyl tRNA. AB - An RNA moiety has been shown to be involved in the conversion of Glu to delta aminolevulinic acid (ALA), the first committed intermediate of the chlorophyll pathway. We now have evidence suggesting that in Chlamydomonas, the first reaction for converting Glu to ALA is the aminoacylation of Glu to a Glu-specific tRNA. The Glu-tRNA thus formed could be the substrate for Glu-1-semialdehyde synthesis catalyzed by a postulated dehydrogenase. Glu-1-semialdehyde can be converted to ALA by an aminotransferase. Of the three reactions converting Glu to ALA, only the second reaction, catalyzed by a postulated dehydrogenase, is sensitive to inhibition by heme (a known inhibitor of ALA synthesis). We think the regulated enzyme of ALA synthesis is the postulated dehydrogenase. It is postulated that in the chloroplast of Chlamydomonas, the synthesis of ALA and the synthesis of proteins may share a common pool of glutamyl-tRNA. PMID- 2875999 TI - Gamma-glutamyl-glutathione. Natural occurrence and enzymology. AB - The natural occurrence of gamma-glutamyl-glutathione (gamma-glutamyl-gamma glutamylcysteinylglycine) in bile was established by analytical and chromatographic studies on the isolated and chemically synthesized materials. Evidence that it is formed in kidney was obtained. The origin of gamma-glutamyl glutathione was explored through studies on the interaction of glutathione with gamma-glutamyl transpeptidase. When purified gamma-glutamyl transpeptidase was incubated with various concentrations (4 microM-50 mM) of glutathione, the initial rates of formation of gamma-glutamyl-glutathione were substantial at all concentrations of glutathione studied and were greater than the rates of formation of glutamate at physiological levels of glutathione (1-10 mM). The findings indicate that gamma-glutamyl transpeptidase catalyzes transpeptidation in vivo. That gamma-glutamyl-glutathione is formed in vivo and that it is a significant product of the reaction between glutathione and gamma-glutamyl transpeptidase under physiological conditions suggest that this polyanionic tetrapeptide may have a physiological role. gamma-Glutamyl-glutathione is not a substrate of glutathione reductase or of glutathione S-transferase, but it is a substrate of gamma-glutamyl-cyclotransferase. That gamma-glutamyl-glutathione has an additional negative charge as compared to glutathione suggests that it may be more effective than glutathione in forming complexes with certain metal ions and other cations. PMID- 2876000 TI - An antigen-conserving ELISA for detecting human antibodies to Bordetella pertussis filamentous hemagglutinin. PMID- 2876001 TI - Circulating catecholamines modulate ischemic brain damage. AB - In search of factors influencing the outcome of an ischemic insult, we induced 10 min of forebrain ischemia in rats and assessed neuronal necrosis by quantitative histopathology after 1 week of recovery. Procedures for inducing ischemia included bilateral carotid artery clamping and reduction of blood pressure to 40 50 mm Hg by bleeding. To facilitate rapid lowering of blood pressure, a ganglionic blocker, trimethaphan (TMP), was administered at the onset of ischemia. Omission of the ganglionic blocker proved to markedly ameliorate neuronal damage. Similarly favorable effects were obtained when a mixture of adrenaline and noradrenaline (1 microgram kg-1 min-1 each) was infused during the early recirculation period in animals previously given TMP. Infusion of noradrenaline alone also ameliorated the damage, though the efficacy was somewhat less. The results suggest that catecholamines, released as a response to stress, ameliorate ischemic brain damage. PMID- 2876002 TI - Drug-induced hyperkalemia. AB - This is the era of polypharmacy. Treatment with multiple therapeutic agents for multiple underlying medical conditions leads to greater vulnerability to such metabolic imbalances as hyperkalemia. The physician must know which underlying medical conditions and drugs predispose to abnormal intracellular-extracellular potassium balance and abnormal regulation of potassium excretion. PMID- 2876003 TI - Semipreparative separation of cyclic carbamates of beta-blocking agents by liquid chromatography on swollen microcrystalline triacetylcellulose. PMID- 2876004 TI - Automated high-performance liquid chromatographic method with column switching for the determination of neurotransmitters and related compounds, ascorbic acid and uric acid in tissue extracts. AB - An automated high-performance liquid chromatographic method with electrochemical and fluorimetric detection and on-line data evaluation is described for the simultaneous measurement of indoleaminergic and catecholaminergic neurotransmitters, some of their metabolites and precursors and ascorbic and uric acids. Deproteinized tissue extracts from the central nervous system or peripheral organs are injected without prior purification (recovery greater than 90%). A switching system enables the compounds to be passed as necessary through one, two or three reversed-phase columns, which are then eluted simultaneously (analysis time 25 min). Fifty samples per day can be analysed with a precision of 95% for neurotransmitters and about 90% for ascorbic and uric acids. PMID- 2876005 TI - Somatostatin analog SMS 201-995 and insulin needs in insulin-dependent diabetic patients studied by means of an artificial pancreas. AB - SMS 201-995 is a new somatostatin analog which is 10-60 times more potent and specific than somatostatin as an inhibitor of GH and insulin release. The aim of this study was to assess its value as an adjunct to insulin therapy in insulin dependent diabetic- (IDD) patients. Six IDD patients were studied. Their average insulin doses ranged from 22-46 U/day, and hemoglobin A1c levels varied between 6.5-11.5%. Two patients had background retinopathy and mild sensorimotor neuropathy. After 12 h of glucemic stabilization, the patients were kept normoglycemic by connecting them to the Biostator-GCIIS. The study entailed two parts in random order, in which standardised mixed meals were administered at 0800, 1400, and 2000 h with or without sc bolus injections of 50 micrograms SMS 201-995 immediately before meal ingestion. Plasma free insulin, C-peptide, GH, and glucagon were measured by RIA. Postprandial hyperglycemia was significantly diminished by SMS 201-995 after breakfast, lunch, and dinner. Insulin requirements, both total and 2-h postprandially, decreased significantly with a parallel reduction in free insulin levels. Postprandial glucagon levels also significantly decreased, but GH profiles were similar. In conclusion, the somatostatin analog SMS 201-995 has a potential value as an adjunct to insulin in the management of IDD patients. PMID- 2876006 TI - Distribution of isoforms of the myofibrillar proteins in myoid cells of thymus. AB - Myoid cells of calf and rat thymus have been identified by staining with a monoclonal antibody to the heavy chain of myosin that is not isoform specific. Heterogeneity in the protein composition of myoid cells has been demonstrated by staining with antibodies to the skeletal muscle isoforms of the myosin heavy chain, C-protein and components of the troponin complex. The immunochemical studies suggest that the myoid cells contain proteins closely resembling if not identical with those present in the myofibrils of skeletal muscle. The slow and fast skeletal muscle isoforms of the myofibrillar proteins are present in a large proportion of the myoid cells. A fraction of the myoid cells contains only the fast isoforms of the myofibrillar proteins but there is no sharp compartmentalization of the isoforms as occurs in type 1 and type 2 fibres of skeletal muscle. In general the pattern of gene expression is similar to that of developing skeletal muscle. PMID- 2876007 TI - Individualization: the categorical imperative of behavior therapy practice. AB - The fact that unadaptive neurotic anxiety response habits are learned makes it necessary for the stimulus antecedents to be accurately defined in every case in order to plan effective treatment. This requirement has been frequently neglected in recent years that have witnessed a growing tendency to apply common treatments to cases with common labels, e.g. agoraphobia. This paper argues for the desirability of accurate individual diagnosis, and illustrates its benefits in unique cases and also in respect of three common syndromes--agoraphobia, panic attacks and depression. PMID- 2876008 TI - A generic computer program for systematic desensitization: description, construction and case study. AB - A computer program designed to provide systematic desensitization for phobias is described. Clients are taught by computer-aided instruction to develop their own personalized phobic hierarchy which is then used by the computer as the phobic stimulus in desensitization proper. The results of a pilot trial with an agoraphobic client indicate that the computer program was successful. PMID- 2876009 TI - The use of systematic desensitization to overcome resistance to magnetic resonance imaging (MRI) scanning. AB - The use of behavioral techniques with radiologic procedures has received surprisingly little attention in the behavioral literature. The current paper describes the successful use of systematic desensitization to enable a woman to complete a magnetic resonance imaging (MRI) scan. Suggestions for when behavior therapy may be useful to radiologists are also given. PMID- 2876010 TI - Assessment and treatment of multiple behavior problems exhibited by a profoundly retarded adolescent. AB - The severe aggression and noncompliance of a profoundly retarded blind male were subjected to extensive behavioral assessment in order to identify controlling variables. The assessment, conducted across settings and therapists, suggested that these inappropriate behaviors functioned to avoid or terminate nonpreferred activities. Intervention consisted of manual guidance when there was noncompliance with instructions and edible reinforcement upon compliance; there were no direct contingencies for the inappropriate behaviors. Treatment procedures were implemented in a multiple baseline design across therapists and settings. Results show that the intervention consistently increased compliance, with concurrent decreases in inappropriate behaviors. Edible reinforcement and neuroleptic medication were withdrawn systematically with no loss of therapeutic gains. Family members and school personnel were trained to use the intervention procedures. Results are discussed in terms of functional assessment, response covariation, compliance training, parent and staff training, and behavioral assessment of the effects of neuroleptic medication. PMID- 2876011 TI - Diabetes and schizophrenia--a preliminary study. AB - The results of a small scale retrospective study are presented. The study was initiated to determine the incidence of diabetes in long-stay patients in two psychiatric hospitals in Northern Ireland and to attempt to define whether there was a relationship between the two disease states, schizophrenia and diabetes mellitus. There was a higher percentage of diabetics in the two institutions than was expected. It was concluded that drug therapy of the mental illness may have had a contributory effect on the subsequent development of diabetes mellitus. PMID- 2876012 TI - Organization of tyrosine-hydroxylase immunopositive neurons in the brain of the crested newt, Triturus cristatus carnifex. AB - The localization of neurons, fibers, and terminals containing tyrosine hydroxylase (TH)-like immunoreactivity was studied in the brain of the crested newt by using an antiserum to rat phaeochromocytoma tyrosine hydroxylase. Immunoreactive cells and fibers were found in the spinal cord, the medulla oblongata (lateral periventricular areas), and the acousticolateral area. In the tegmentum mesencephali, two bilateral clusters of labelled cells were localized in the ventrolateral periventricular gray extending toward the caudal hypothalamus. In the hypothalamic tuberal lobes, the TH-like reactive neurons, frequently of CSF-contacting type, lined the dorsal wall of the lateral infundibular recesses. A thick network of TH-like reactive nerve fibers and terminals was observed in the perivascular zone of the median eminence and in the adenohypophysial pars intermedia. A number of labelled cell bodies were also found in the dorsal thalamus (pars intercalaris diencephali), the paraventricular organ, and the ventral wall of the preoptic recess. In the telencephalon, immunoreactive innervation was identified in the striatum, together with immunopositive cell bodies in the olfactory bulbs. The pattern of organization of TH-immunoreactive systems in the newt showed, except for some peculiarities (e.g., the labelled cell bodies in dorsal thalamus), close similarities to the arrangement typical of mammals. PMID- 2876013 TI - Action spectra of photoactivated cyclic GMP metabolism and relaxation in bovine mesenteric artery. AB - Strips of bovine mesenteric arteries, brought to sustained contraction by addition of 3.0 microM phenylephrine, relaxed during exposure to shortwave light. The action spectrum of the photorelaxation was characterized by most effectiveness of relaxation in the range of 360 to 400 nm; on the contrary, shortwave light of 280 to 300 nm increased the tension. The photo-induced relaxation was accompanied by an increase in the cGMP level, measured 30 sec after the onset of radiation, and the action spectrum of the increase in cGMP seemed to coincide fairly well with the action spectrum of relaxation. Both the increase in cGMP and relaxation in response to increasing light intensity at 400 nm fitted the rectangular hyperbolic equation. The K values (the intensity which gave half maximal response) for cGMP increase and relaxation, respectively, obtained by non-linear least square regression analysis, were found to assume very close values (1.3 mW/cm2 for cGMP increase and 1.5 mW/cm2 for relaxation). The action spectrum of the crude soluble guanylate cyclase (GC) activity displayed a peak around 400 nm. Our results suggest that there is a close association between photo-induced increase in cGMP and relaxation, probably as a result of interaction between shortwave light and the heme moiety of GC. PMID- 2876014 TI - Desensitization in rat parotid to beta-adrenergic agonists and counteracting effects of forskolin are conserved in membrane and detergent-solubilized adenylate cyclase catalyst activity. AB - Cyclic AMP accumulation in rat parotid slices is only transiently stimulated by isoproterenol (Harper, J.F. and Brooker, G. Molec. Pharmacol. 13:1048-1059, 1977); the progressive loss of isoproterenol effect is termed desensitization. In this report we show that desensitized cyclic AMP accumulation is associated with desensitization of adenylate cyclase in subsequently prepared membranes and in adenylate cyclase that has been detergent-solubilized from desensitized membranes. Adenylate cyclase in membranes made from isoproterenol-desensitized tissue is desensitized to both the stimulating effects of isoproterenol with 6 mM MgCl2 and of forskolin with 30 mM MnCl2. We have previously determined (Harper, J.F. J. Cyclic Nucleo. Prot. Phosphoryl. Res. 9:401-414, 1984) that cyclic AMP accumulation desensitized to isoproterenol is rapidly counteracted by 1 microM forskolin but not 0.1 microM forskolin. Similarly, if 1 microM forskolin was included in the desensitizing incubation with isoproterenol then adenylate cyclase subsequently prepared was not desensitized. Development of desensitized adenylate cyclase was only partially affected by 0.1 microM forskolin. Desensitization is counteracted by forskolin only on intact cells. Once tissue is homogenized, desensitized adenylate cyclase does not respond as well to forskolin as does control adenylate cyclase. The site of desensitization appears to be at or near the adenylate cyclase catalytic unit. Desensitization of adenylate cyclase catalytic activity remains demonstrable after membranes are solubilized with CHAPS. The adenylate cyclase activity remaining in the supernatant following solubilization of desensitized membranes is depressed to nearly the same extent as found in the membranes. Further, desensitized adenylate cyclase in membrane preparations and after solubilization is desensitized to stimulatory effects of forskolin with 30 mM MnCl2, a condition under which forskolin is probably acting directly on the adenylate cyclase catalytic unit. Desensitization appears not to be dependent on activity of the inhibitory guanine nucleotide regulatory protein (Gi), since pertussis toxin is without effect on desensitization of cyclic AMP accumulation to isoproterenol. PMID- 2876015 TI - Role of cyclic GMP in gastrin secretion from rat antral mucosae in organ culture. AB - Rat antral mucosae maintained for 6 h in organ culture responded to carbamylcholine with a significant increase in endogenous cyclic GMP production and gastrin secretion. The acetylcholine analogue exerted a stimulatory action within a defined concentration range: exposure of antral explants to carbachol concentrations greater than the optimal stimulatory dose was accompanied by a marked decrease in both cyclic GMP production and gastrin release. Exogenous 8-Br cyclic GMP (1 mM) significantly augmented gastrin secretion into the culture media during 6-12 h culture periods. Cycloheximide (0.1 mM) and the Ca2+ channel blocker verapamil (5 microM) prevented 8-Br-cyclic GMP from acting as a gastrin secretagogue. Addition of cyclic somatostatin-14 (0.1 mM) to culture media was attended by complete inhibition of 8-Br-cyclic GMP-stimulable gastrin secretion. These results provide evidence that cyclic GMP may play a mediatory role in the coupling of gastrin secretory processes to agonist stimulation. It would seem that the secretagogue action of 8-Br-cyclic GMP requires unabated Ca2+ transmembrane fluxes and protein biosynthesis. Since somatostatin-14 abrogates the stimulatory effect of 8-Br-cyclic GMP on antral gastrin secretion, it is surmised that the inhibitory tetradecapeptide acts at a locus (or loci) distal to domains involved in the actual generation of the cyclic nucleotide. PMID- 2876016 TI - Medication: its role in the cause and treatment of urinary incontinence. PMID- 2876017 TI - Functional consequences and intracoronary localization of alpha-adrenergic stimulation of the canine coronary circulation. AB - Although alpha-adrenergic stimulation can increase coronary vascular resistance, it remains unknown whether the vasoconstriction can override intrinsic coronary regulatory influences to produce ischemia. Methoxamine, 2 to 4 mg, was infused into the circumflex coronary artery of 23 chloralose-anesthetized open chest dogs, and resulted in a 68% increase in coronary vascular resistance. The functional consequence of this increased coronary vascular resistance was assessed by gated radionuclide ventriculography and ST-T wave changes on the electrocardiogram. In six dogs (Group I), aortic pressure changed trivially (less than 5 mm Hg) to allow distinction between direct effects of the flow reduction and indirect effects of increased aortic pressure. In this group, coronary blood flow decreased 33% from a control value of 44 +/- 10 ml/min (p less than 0.001) and left ventricular ejection fraction decreased from 0.54 +/- 0.12 to 0.46 +/- 0.10 (p less than 0.025). In eight dogs (Group II) in which aortic pressure increased by more than 5 mm Hg, left ventricular ejection fraction decreased from 0.46 +/- 0.07 to 0.39 +/- 0.09 (p less than 0.002). Pressure gradients were measured between the aorta and a distal coronary artery branch to calculate small and large vessel resistances separately in four other dogs (Group III). The resistance of small coronary arteries accounted for 92% of the total increase in coronary vascular resistance produced by methoxamine. In five other dogs (Group IV), intracoronary methoxamine, 2 mg, produced ST-T wave changes suggestive of ischemia as it increased coronary vascular resistance by 33%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876018 TI - Prognostic significance of the treadmill exercise test performance 6 months after myocardial infarction. AB - A submaximal treadmill exercise test performed before hospital discharge after an uncomplicated myocardial infarction is often utilized to estimate prognosis and guide management, but there is little experience with a maximal exercise test performed 6 months after infarction to identify prognosis later in the convalescent period. The performance characteristics during an exercise test 6 months after myocardial infarction were related to the development of death, recurrent nonfatal myocardial infarction and coronary artery bypass surgery in the subsequent 12 months (that is, 6 to 18 months after infarction) in 473 patients. Mortality was significantly greater in patients who exhibited any of the following: inability to perform the exercise test because of cardiac limitations, the development of ST segment elevation of 1 mm or greater during the exercise test, an inadequate blood pressure response during exercise, the development of any ventricular premature depolarizations during exercise or the recovery period and inability to exercise beyond stage I of the modified Bruce protocol. By utilizing a combination of four high risk prognostic features from the exercise test, it was possible to stratify patients in terms of risk of mortality, from 1% if none of these features were present to 17% if three or four were present. Recurrent nonfatal myocardial infarction was predicted by an inability to perform the exercise test because of cardiac limitations, but not by any characteristics of exercise test performance. Coronary artery bypass surgery was associated with the development of ST segment depression of 1 mm or greater during the exercise test. Although clinical evidence of angina and heart failure 6 months after infarction was predictive of subsequent mortality among all survivors, among the low risk group without severely limiting cardiac disease, the exercise test provided unique prognostic information not available from clinical assessment alone. Therefore, a maximal exercise test performed 6 months after myocardial infarction is a valuable, noninvasive tool to evaluate prognosis. It provides information that is independent of and additive to clinical evaluation performed at the same time. PMID- 2876019 TI - Patterns of symptoms and prognosis in occlusive thromboaortopathy (Takayasu's disease). AB - Ninety-five Japanese patients with Takayasu's disease were classified according to four patterns of severity of symptoms in the period from the onset of symptoms to diagnosis. Included were pattern A in 34 patients with a plateau course after the insidious onset of symptoms, pattern B in 18 patients with a decrescendo course after the sudden onset of severe symptoms, pattern C in 5 patients who had no severe symptoms during the years between the early and late periods of severe symptoms and pattern D in 38 patients with a crescendo course after the onset of symptoms and the following period of years of no severe symptoms. Fifteen patients died during the prospective follow-up period of 8.6 +/- 6 years (mean +/ SD) after admission, but 12 had had patterns C and D and the remaining 3 had had patterns A and B. The cardinal signs and symptoms are given in detail, particularly those at the onset. These data should aid in early diagnosis and prediction of the prognosis in Takayasu's disease. PMID- 2876020 TI - Patterns and timing of Doppler-detected intracavitary and aortic flow in hypertrophic cardiomyopathy. AB - This study describes the velocity characteristics of left ventricular and aortic outflow in 25 patients with hypertrophic "obstructive" cardiomyopathy. Systematic pulsed and continuous wave Doppler analysis combined with phonocardiography and M mode echocardiography was used to establish the pattern and timing of outflow in the basal and provoked states. This analysis suggests that 1) the high velocity left ventricular outflow jet can be reliably discriminated from both aortic flow and the jet of mitral regurgitation using Doppler ultrasound; 2) the Doppler velocity contour responds in a characteristic fashion to provocative influences including extrasystole and Valsalva maneuver; 3) the onset of mitral regurgitation occurs well before detectable systolic anterior motion of the mitral valve; 4) left ventricular flow velocities are elevated at the onset of systolic anterior motion of the mitral valve, suggesting a significant contribution of the Venturi effect in displacing the leaflets and chordae; 5) the high velocities of the outflow jets are largely dissipated by the time flow reaches the aortic valve; and 6) late systolic flow in the ascending aorta is nonuniform, with formation of distinct eddies that may contribute to "preclosure" of the aortic valve. PMID- 2876021 TI - Heart rate, blood pressure regulation and neurotransmitter balance in Tourette's syndrome. PMID- 2876022 TI - T cell subsets and thyroid-stimulating antibodies in patients with Graves' disease in clinical remission. AB - Patients with active Graves' disease almost constantly show phenotypic alterations of T lymphocytes, such as an increase of "activated" cells recognized by various surface markers (e.g. la antigens). Such alterations are present in a certain number of apparently cured patients. The data herein reported refer to 25 patients with Graves' disease in clinical remission, in whom we have attempted to correlate T cell subset imbalances, the presence of thyroid-stimulating antibodies (TSAb) and the outcome of the subsequent relapse. The results obtained show a significant association between TSAb and the increase of la-positive T cells: no relationship was found between TSAb and other T lymphocyte subsets. One year clinical follow-up of the patients enabled us to see relapses of hyperthyroidism in only two patients, who had shown in the first control both TSAb positivity and increased la-positive T cells. These results, in our opinion, suggest a role of la antigens expression on T lymphocytes in the clinical course of Graves' disease. PMID- 2876024 TI - Peptic ulcer. A follow-up study. AB - One hundred and ten patients who had been entered into an ulcer healing study 2 to 4 years previously were recalled during an 8-week period for clinical assessment and endoscopy. Fifty-five gastric ulcer patients were followed-up after an average period of 21.2 months. Nine of these had undergone gastric surgery; of the remaining 46 patients, recurrent ulceration was found in 16 (35%). Fifty-five patients with duodenal ulcer disease were also followed-up after an average of 35.6 months. Five of these patients had undergone surgery and of the remaining 50, 25 (50%) had a recurrent duodenal ulcer. About one-third of both gastric and duodenal ulcer recurrences were asymptomatic. Smoking had no effect on recurrence rates. PMID- 2876023 TI - Acid rules--or does it? PMID- 2876026 TI - Control of Legionella in hospitals. AB - Legionellas are present in water distribution systems and cooling towers of many hospitals. No firm data are available regarding the need for prophylactic disinfection of these contaminated systems. Disinfection of water systems and cooling towers is an accepted and effective means of ending nosocomial Legionnaires' disease, but it should be performed in conjunction with good epidemiological and microbiological studies to pinpoint environmental reservoirs and disseminators. Chlorination, pasteurization, or both, are the only means of disinfection found to be effective in disease outbreaks. Prospective surveillance of immuno compromised patients with pneumonia is probably the most effective means to determine if a hospital is a source of Legionnaires' disease and, therefore, requires further investigations and disinfection. PMID- 2876027 TI - Nosocomial infection control in the United States of America. PMID- 2876025 TI - Cytogenetic and isozyme profile of Sabethes cyaneus: a mosquito of the neotropical canopy. AB - Sabethes cyaneus, a newly colonized culicine mosquito from the Panamanian forest canopy, has a distribution range from Honduras to Argentina. Cytogenetic studies, the first on any Sabethes species, revealed a karyotype of three pairs of homomorphic chromosomes (2n = 6). Well-developed polytene chromosomes were discovered in the larval salivary glands and a photomap standard was constructed. Clear banding patterns and consistent landmarks distinguished each of the six arms. Substantial asynapsis occurred in the three polytene chromosomes, although the banding pattern of the homologous regions appeared homosequential. A nucleolar organizer was localized in region 5A of the shortest chromosome by the recurrent association of this region with the nucleolus. The large band in region 5A was found heterozygous for width and a deletion. Additional, less conspicuous, polymorphisms for band width and staining intensity were distributed throughout the genome. Biochemical studies of 31 enzyme loci revealed 10 loci to be polymorphic, with an average heterozygosity of 13 percent. Differential expression in developmental stages occurred for 11 loci involving six enzymes. PMID- 2876028 TI - An outbreak of tuberculosis in a children's hospital. AB - A 3-year-old girl was admitted to a children's hospital; subsequently her mother was found to have pulmonary tuberculosis with smear-positive sputum. Of over 400 patients, their families and staff at risk in the hospital, 30 inpatients, three outpatients, two sibling visitors and one staff member became infected. A retrospective cohort study of exposed inpatients identified exposure duration, exposure proximity and primary diagnosis as independent predictors of infection risk. Children with neoplastic disease who were being treated with cytotoxic and immunosuppressive therapy with clotting factors were at a greater risk of developing clinical disease including disseminated infection. Altogether three generations of infected children and adults were diagnosed amongst community and hospital contacts in this extended outbreak. These findings support current recommendations for the follow-up of highly susceptible casual contacts of cases of pulmonary tuberculosis with smear-positive sputa. PMID- 2876029 TI - Methicillin-resistant Staphylococcus aureus in the UK and Ireland. A questionnaire survey. AB - The results of a questionnaire survey of the distribution of methicillin resistant Staphylococcus aureus (MRSA) in the UK and Ireland between 1982 and 1983 are reported. Information was obtained about the geographical distribution of MRSA, the units affected, the sites of isolation and the preventive measures employed. Serious clinical problems were confined to a small number of hospitals with high isolation rates of MRSA. PMID- 2876030 TI - A study of the skin flora of spinal cord injured patients. AB - The skin flora of 11 spinally-injured patients was compared to that of 11 healthy control subjects. The perinea, groins, penile shafts and urethras of the patients were heavily colonized by a range of multi-drug resistant Gram-negative bacilli. Observations on patients from admission for up to 25 days suggest that the Gram negative bacilli start to colonize the skin 2-3 days after admission. Some species, e.g., Citrobacter diversus and Escherichia coli appear as transient organisms while others such as Enterobacter aerogenes, Serratia marcescens, and Klebsiella pneumoniae seem to become stable skin residents. The relationship of the skin flora to the organisms causing urinary tract infections in these patients was studied. PMID- 2876031 TI - Antibiotic costs and prescribing patterns in a recently commissioned Liverpool teaching hospital. Part I: Antimicrobial therapy. AB - All antibiotics prescribed in a major teaching hospital were prospectively surveyed during 31 consecutive days. Of 2350 patients admitted during that period, 577 (24.6%) received antibiotics, 238 (10.1%) for prophylaxis and 417 (17.7%) for treatment. A total of 483 infections occurred in the treated patients, mainly in the chest (33.9%) and urinary tract (27.7%). Two hundred and forty-four infections (50.5%) were community-acquired and the remaining 239 hospital-acquired infections occurred in 8% of patients admitted. The cost of treating nosocomial sepsis was 4453 pounds (48% of the antibiotic expenditure for treatment). The average cost of treatment per patient varied considerably between hospital specialties; one-third of therapeutic antibiotic expenditure was consumed by haematological patients. Thirty-one antimicrobials alone or in 45 different combinations were issued; ampicillins were the most frequently prescribed antibiotics (31%), followed by co-trimoxazole (14%) and trimethoprim (8%). The patterns of antibiotic usage are discussed and inappropriate prescriptions examined. PMID- 2876032 TI - Antibiotic costs and prescribing patterns in a recently commissioned Liverpool teaching hospital. Part II: Antimicrobial chemoprophylaxis. AB - All antibiotics prescribed for prophylaxis in a major teaching hospital were prospectively surveyed during 31 consecutive days. Of 2350 patients admitted during that period, 238 (10.1%) received antibiotics for prophylaxis. A total of 1238 operations were performed during the period of study, of which 201 (16.2%) were covered with antibiotics, at a cost of 3472 pounds. The use of prophylaxis increased according to the risk of peri-operative wound contamination, from 15.8% in Class I to 52.4% in Class III operations. The average cost of chemoprophylaxis also increased correspondingly. A further 40 regimens were issued for non surgical prophylaxis at a cost of 258 pounds. Twenty antibiotics were prescribed either alone or in 37 different combinations for surgical prophylaxis, the most frequent being cephradine (22%), metronidazole (17%), penicillin (12%), and tobramycin (11%). The mean duration of antibiotic administration for all surgical procedures was 6.1 days. PMID- 2876033 TI - Blood contamination during venepuncture and laboratory manipulations of specimen tubes. AB - The contamination of the working environment was assessed using a forensic screening test for blood during venepuncture, transport and laboratory manipulation of specimen tubes. Different methods of collecting blood and different commercially available specimen tubes were also assessed using an in vitro system. Blood collected by needle and syringe caused more environmental contamination than did an evacuated container system. Of the commercially available specimen tubes, those with screw tops produced least environmental contamination. PMID- 2876034 TI - Per-operative antibiotic treatment in cardiovascular surgery: the influence of methicillin versus cephalothin on post-operative infections and bacterial colonization. AB - This paper reports the results of a prospective study of antibiotic prophylaxis in 543 patients undergoing open-heart surgery. All patients were given per operatively either methicillin, 1 g four times a day, or cephalothin, 1 g four times a day. There was no significant difference in the frequency of postoperative infections between the two groups. It was established that per operative antibiotic prophylaxis selected resistant coagulase-negative staphylococci (CNS) in the nasal flora of cardiac surgery patients, that this change occurred to the same degree whether methicillin or cephalothin was used, that cephalothin favoured colonization with antibiotic resistant species other than CNS. It was found that the staff of the intensive care unit formed a reservoir of multi-resistant CNS. PMID- 2876035 TI - Effects of various doses of latamoxef (moxalactam) on haemostasis. AB - The effects of intravenous latamoxef therapy at two doses of 3g and 6g daily for 7 days was assessed by various haemostatic parameters. With both doses, the prothrombin time, thrombin time and activated partial thromboplastin time remained within the normal range throughout the study. However, with the 6g day-1 dose there was a marked prolongation of the bleeding time associated with defective platelet aggregation to adenosine diphosphate and low dose collagen after 7 days therapy. With the 3g day-1 dose of latamoxef, there was no prolongation of the bleeding time and only minor changes in platelet aggregation responses. PMID- 2876037 TI - Pour plate blood cultures to detect bacteraemias related to indwelling central venous catheters. PMID- 2876036 TI - Microbiological tests on operating-theatre staff of a new disinfectant foam based on 1% chlorhexidine gluconate. AB - A pre-operative topical application of a foam containing 1% chlorhexidine gluconate in 50% ethanol to the hands and forearms was compared with a 4% chlorhexidine gluconate scrub. When these sites were sampled after 1 h of operating with gloves, no difference in the rates of recovery of Staphylococcus epidermidis between the two groups was found. PMID- 2876038 TI - Group B streptococcal bacteraemia associated with a triple lumen intravenous catheter. PMID- 2876039 TI - T cell independent Thy-1 allo-antibody response with the use of transgenic mice. AB - We have introduced a mouse Thy-1.1 gene into the germline of Thy-1.2 mice. The introduced gene was shown to be expressed at very high levels in thymocytes when compared with the endogenous gene. Transgenic thymocytes were shown to evoke a higher than normal primary anti-Thy-1.1 antibody response in plaque-forming cell (PFC) assays. This result suggests that a direct quantitative interaction of the Thy-1 antigen activates the B cell response. PMID- 2876040 TI - Interleukin 3 is a major negative regulator of the generation of natural killer cells from bone marrow precursors. AB - We have established a bone marrow culture system in which mature natural killer (NK) cells can be generated from inactive precursors by interleukin 2. Recombinant interleukin 3 (IL 3) almost completely blocked the induction of NK cells in this culture system as judged by cytotoxic activity, as well as appearance of cells with NK phenotype. The dose-response curve for inhibition of the generation of NK activity with IL 3 parallelled the growth promoting activity on the strictly IL 3-dependent cell line L/B. The effect of IL 3 was selective for the precursor stage of the NK cell, because mature NK cells were not affected by culture with IL 3 for the same period of time. Moreover, the effect of IL 3 was confined to the first 24 hr of culture, indicating an effect on an early stage of NK cell differentiation. IL 3 did not increase the small normally occurring NK-sensitive population in bone marrow, and did not affect the activity of a variant cytotoxic cell with specificity for adherent target cells, the natural cytotoxic cell. Concomitantly with downregulation of NK cell generation, IL 3 induced strong proliferation in the bone marrow cultures and an increase in the percentage of cells expressing the T cell marker Thy-1. A model for regulation of NK cells based on competition of growth factors for target cells with a common progenitor is discussed. PMID- 2876041 TI - Induction and regulation of contact hypersensitivity by resident, bone marrow derived, dendritic epidermal cells: Langerhans cells and Thy-1+ epidermal cells. AB - Circumstantial evidence suggests strongly that epidermal Langerhans cells (LC) alone among epidermal cells (EC) are responsible for generating an immunogenic signal for contact hypersensitivity (CH) after epicutaneous application of hapten. However, data obtained from previous studies performed with intact skin or isolated EC do not address the immunogenic capacity of a second dendritic, bone marrow-derived population of cells that resides within the epidermis, Thy-1+ epidermal cells. To identify the cellular source(s) of the antigenic signals emerging from the epidermis, purified preparations of LC, Thy-1+ cells, and keratinocytes were prepared from CBA/J mouse skin. Each cell type was derivatized in vitro with TNBS and inoculated via various routes into syngeneic mice that were assayed for the induction of CH and specific unresponsiveness. IA+ LC, when derivatized with hapten and inoculated into mice, induced CH without evidence of down-regulation regardless of the route of immunization. Derivatized Thy-1+ EC did not deliver a positive signal for CH. Rather, Thy-1+ EC possessed the capacity to initiate down-regulation of the CH response when they were delivered i.v. We conclude that all cellular elements necessary for the induction and regulation of CH after epicutaneous application of hapten to skin reside within the epidermis. The resident, dendritic, bone marrow-derived populations within the epidermis have the capacity to determine the outcome of an epicutaneous antigenic encounter. PMID- 2876043 TI - [Relation of colonial morphologies of the strain Ac-0119 of Acinetobacter anitratus in a soft-agar medium and its variants to morphologic and biologic properties]. PMID- 2876042 TI - [Intracavernous injections of vasoactive drugs. Evaluation of their diagnostic and therapeutic value in 65 cases of erectile impotence]. AB - Intracavernous injection (IC) of vasoactive drugs (papaverine (ICP) in 115 cases and different alpha-blockers in 65 cases) were administered to 65 patients with erectile impotence to evaluate diagnostic and therapeutic interest of this procedure. Immediate (induction of erection) and medium term (lasting improvement in impotence) results were correlated with those of investigations of multidisciplinary etiologies. Comparison of results of ICP with those of plethysmography of nocturnal erections (PEN, 52 cases) gave negative results for the papaverine test (lack of erection or one without rigidity) in 67% of cases of impotence of organic origin (PEN abnormal). However, the test was positive (totally rigid erection) in 17% of cases of organic etiology and only 40% of psychogenic cases (PEN abnormal). Comparison of results with those of selective hypogastric arteriography and of the artificial erection test with dynamic cavernography (43 cases) showed that the papaverine test was never positive in patients with severe arterial occlusion or obvious venous leaks. However, an elevated proportion of cases with a negative test failed to show signs of marked vascular anomalies. Integration of results of total multidisciplinary explorations showed that most patients with organic or mixed impotence producing a positive or intermediary type papaverine test were cases of neuropathic impotence or had major neuropathic elements. Repeated IC of different vasoactive drugs (excluding the use of autoinjection techniques) failed to provide lasting improvement except for psychogenic impotence (5 of 9 cases). But it is in this group that IC is the most dangerous (2 cases of priapism and 8 cases of rigid erection prolonged over more than 4 hours).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876044 TI - The Ir-Thy-1 concept: continuing saga. PMID- 2876045 TI - Effect of acivicin on glutamine transport by rat renal brush border membrane vesicles. AB - Acivicin (L-[alpha S,5S]-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid) reversibly and competitively inhibits glutamine transport in rat renal brush border membrane (BBM) vesicles. Acivicin alters the affinity of the low-Km high affinity glutamine transport system, but has minimal effect on the high-Km low affinity system. The drug interferes with glutamine transport by a mechanism that does not involve the maintenance of a Na+-chemical gradient as shown by its uniform effect on glutamine uptake rate, regardless of the NaCl gradient imposed (0 to 150 mmol/L). The effect of acivicin on membrane potential was ruled out by the finding that acivicin modified glutamine transport even when the membrane potential was minimized either by substituting Cl- with an impermeant anion, isethionate, or by short-circuiting the membrane potential with carbonyl cyanide p-trifluoromethoxyphenyl hydrazone. In these experiments the activity of the enzyme gamma-glutamyltranspeptidase (gamma-GT), a component of the putative amino acid transport system, was not suppressed because the BBM was not preincubated with acivicin. Acivicin also interferes with the uptake of other solutes tested (alanine, proline, glutamate, and glucose). But with the exception of L-alanine, the transport of these solutes is less sensitive to the inhibitory effect of acivicin than is that of glutamine. Our results indicate that acivicin profoundly affects the metabolism of renal tubular cells by its influence on the metabolite transport systems. Acivicin can reduce renal NH3 production independently of its effect on gamma-GT by interfering directly with renal cellular uptake of glutamine. PMID- 2876046 TI - Influence of the amino acid moiety on deconjugation of bile acid amidates by cholylglycine hydrolase or human fecal cultures. AB - The influence of the chemical structure of the amino acid (or amino acid analogue) moiety of a number of synthetic cholyl amidates on deconjugation by cholylglycine hydrolase from Clostridium perfringens was studied in vitro at pH 5.4. Conjugates with alkyl homologues of glycine were hydrolyzed more slowly as the number of methylene units increased (cholylglycine greater than cholyl-beta alanine greater than cholyl-gamma-aminobutyrate). In contrast, for conjugates with the alkyl homologues of taurine, cholylaminopropane sulfonate was hydrolyzed slightly faster than cholyltaurine, whereas cholylaminomethane sulfonate was hydrolyzed much more slowly. When glycine was replaced by other neutral alpha amino acids, rates of hydrolysis decreased with increasing steric hindrance near the amide bond (cholyl-L-alpha-alanine much much greater than cholyl-L-leucine much greater than cholyl-L-valine greater than cholyl-L-tyrosine much greater than cholyl-D-valine). Conjugation with acidic or basic amino acids also greatly reduced the rates of hydrolysis, as cholyl-L-aspartate, cholyl-L-cysteate, cholyl L-lysine, and cholyl-L-histidine were all hydrolyzed at a rate less than one tenth that of cholylglycine. Methyl esterification of the carboxylic group of the amino acid moiety reduced the hydrolysis, but such substrates (cholylglycine methyl ester and cholyl-beta-alanine methyl ester) were completely hydrolyzed after overnight incubation with excess of enzyme. In contrast, cholyl-cholamine was not hydrolyzed at all, suggesting that a negative charge at the end of the side chain is required for optimal hydrolysis. Despite the lack of specificity for the amino acid moiety, a bile salt moiety was required, as the cholylglycine hydrolase did not display general carboxypeptidase activity for other non-bile acid substrates containing a terminal amide bond: hippuryl-L-phenylalanine and hippuryl-L-arginine, as well as oleyltaurine and oleylglycine, were not hydrolyzed. Fecal bacterial cultures from healthy volunteers also hydrolyzed cholyl-L-valine and cholyl-D-valine more slowly than cholylglycine, suggesting that cholylglycine hydrolase from Clostridium perfringens has a substrate specificity similar to that of the deconjugating enzymes of the fecal flora. The results indicate that modification of the position of the amide bond, introduction of steric hindrance near the amide bond, or loss of a negative charge on the terminal group of the amino acid moiety of the bile acid conjugate greatly reduces the rate of bacterial deconjugation in vitro when compared to that of the naturally occurring glycine and taurine conjugates. PMID- 2876048 TI - [Determination of dipeptidyl-peptidase IV in biological materials]. AB - Dipeptidyl-peptidase IV (EC 3.4.14.5) can be assayed relatively specifically in crude biological material by determination of the initial rate of formation of 4 nitroaniline from aminoacyl-proline-4-nitroanilides. For clinical purposes tricine buffer, pH 7.4, is employed, because unspecific cleavage of the substrate is minimal under these conditions. Various types of chromogenic and fluorogenic leaving groups can be used to detect the enzyme on solid supports. During the enzymatic hydrolysis of the tripeptides Xaa-Pro-Yaa, there is an increase of absorbance at 228 nm, which is useful for monitoring the enzyme activity. Enzymic activity can also be measured titrimetrically in unbuffered solutions, whereby corrections must be made for the protonation of both substrate and products. PMID- 2876047 TI - Neonatal exposure to delta 9-tetrahydrocannabinol enhances sexual responses in the adult male mouse. AB - From day 1 post partum to postnatal day 5, lactating female mice were given daily oral doses of 25 microliters sesame oil, 0.5 mg tetrahydro-6,6,9-trimethyl-3 pentyl-6H-dibenzo(b,d)pyran-1-ol (delta 9-tetrahydrocannabinol; THC)/kg or 50 mg THC/kg in 25 microliters oil. Additionally, the pups were given 20 microliter oil, 10 micrograms testosterone or 20 micrograms testosterone in 20 microliter oil s.c. from days 1 to 5 of age. This regimen resulted in nine treatment groups. At 60 days of age, all males were castrated and their testes weighed. After castration, each mouse was implanted s.c. with a 5 mm length of testosterone filled silicone elastomer capsule. When adult they were tested for male copulatory behaviour. Following behavioural testing the animals were bled by cardiac puncture for measurement of plasma testosterone levels, and their hypothalami removed and assayed for dopamine, noradrenaline, 5-hydroxytryptamine (5-HT) and LH-releasing hormone (LHRH). In addition, another two groups of pregnant females were given daily oral doses of 0.5 or 50 mg THC/kg or oil during the first 3 or 5 days of lactation. The male pups were either decapitated for collection of trunk blood or homogenized for determination of serum or whole body testosterone concentrations. Neonatal administration of THC altered adult male sexual responses and had no effect on hypothalamic noradrenaline, 5-HT and LHRH concentrations. There were large increases in serum testosterone concentrations in neonates after maternal THC treatment, although these differences were not significant. Additionally, THC did not influence the testosterone content of neonatal tissue or the testosterone concentration of adult plasma. These results suggest strongly that the effect of THC on male sexual responses is not mediated by its effect on adult hypothalamic neurotransmitter concentrations. Some other potential mechanisms are discussed. PMID- 2876049 TI - Effects of neuroleptic phenothiazines on the activities of aminotransferases and gamma-glutamyltransferase in serum and liver. AB - Serum alanine aminotransferase, aspartate aminotransferase and gamma glutamyltransferase activities were monitored in psychiatric patients receiving normal doses of phenothiazine neuroleptics over a 30-day period. The first two enzymes showed slight initial increases and a subsequent return to normal, while the third showed a slight increase. In rats, dosage levels exceeding those used in human therapy produced much larger increases in the catalytic concentrations of all three enzymes in serum (1.4, 0.7 and 0.5 above the control value, respectively), and somewhat smaller increases in the liver homogenates of these animals. PMID- 2876050 TI - Solute effects on mitochondria from an elasmobranch (Raja erinacea) and a teleost (Pseudopleuronectes americanus). AB - Varying osmolarity with sucrose/KCl media resulted in similar effects on the oxidation of glutamate by mitochondria isolated from the livers of an elasmobranch, Raja erinacea, and a teleost, Pseudopleuronectes americanus. In both species trimethylamine oxide (TMAO) inhibited mitochondrial oxidation of glutamate. Urea penetrated the inner mitochondrial membrane of both species and equilibrated with a ratio ureai/ureao of unity. Urea had little effect on the oxidation of glutamate in both species at concentrations as high as 760 mM. Addition of urea (urea/TMAO, 2:1) did not overcome the detrimental effects of TMAO in the mitochondria of either species. In the case of the elasmobranch, the osmolarity of the urea/TMAO media giving the optimal rate of respiration was hypoosmotic with respect to the intracellular osmolarity. The rate of glutamate oxidation steadily declined as osmolarity increased above this value. Assuming the osmotic profile obtained with the urea/TMAO (2:1) medium resembled most closely the in vivo situation, higher rates of oxidation or organic solutes at low osmolarity would help deplete the cell of these solutes and could contribute to cell volume regulation during hypoosmotic stress. It is suggested that two broad classes of intracellular solutes can be defined based on their effects on mitochondrial respiration. Solutes such as K+, C1-, and TMAO penetrate the inner mitochondrial membrane slowly or not at all. Increasing concentrations of these solutes result in lower rates of oxidation. This capacity may be important in regulating intracellular levels of organic solutes during osmotic stress. Solutes such as urea rapidly penetrate the cell and inner mitochondrial membrane reducing the mitochondrial volume changes associated with osmotic stress. The known detrimental effects of urea on protein structure may prevent its exclusive use as an intracellular osmotic effector. PMID- 2876051 TI - Comparison of restriction site polymorphisms among clinical isolates and laboratory strains of human cytomegalovirus. AB - We have compared HindIII and EcoRI restriction sites in the long and short unique regions of the human cytomegalovirus (HCMV) genome among 20 low passage clinical isolates and four high passage laboratory strains (AD169, Davis, Towne, UW-1). This was done by hybridizing digested DNA on Southern blots with a series of subgenomic cloned fragments of AD169. Fourteen HindIII sites were conserved and three fragments (O, V, W) co-migrated among all strains. Nine HindIII sites found in AD169 were absent in one or more other strains. Eight additional HindIII sites were identified and three more hypothesized by the appearance of slightly smaller fragments. Sixteen EcoRI sites were conserved and six fragments (c, Y, S, W, B, R) co-migrated among all strains. Twelve EcoRI sites were absent or in altered locations and at least seven additional sites were identified in one or more strains. Although no two of these strains were identical throughout the genome, identical patterns of variation in a given region frequently occurred in multiple strains. Polymorphisms occurred throughout the entire genome, including the region specifying immediate early functions. All strains studied showed an identical fragment which hybridized to the transforming fragment of AD169. These restriction site polymorphisms may in the future serve as convenient markers for identification of functional variation among HCMV strains. PMID- 2876052 TI - Excitatory amino acid neurotransmitters in the corticostriate pathway: studies using intracerebral microdialysis in vivo. AB - The concentration of extracellular excitatory amino acids in the striatum of conscious, unrestrained rats was measured using intracerebral microdialysis, during chemical stimulation of the striatum in intact and hemidecorticate animals. Chemical stimulation of the striatum with tityustoxin (0.1 microM) evoked a rise in dialysate concentration of glutamate (to 383% of basal) and aspartate (to 156% of basal), accompanied by a drop in glutamine (to 55% of basal). These changes showed significant attenuation after treatment with L proline (1 mM) or 2-chloroadenosine (15 microM). Unilateral degeneration of the corticostriate pathway, produced by frontal hemidecortication, caused a reduction in both basal and stimulated levels of glutamate in the lesioned side, whereas no effect was observed in the intact side. Similarly, basal and stimulated levels of glutamine were unchanged in the intact side, but were increased in the lesioned side. These results provide in vivo evidence for glutamate and possibly aspartate being neurotransmitters in the corticostriate pathway. In addition they lend support to previous studies in vitro, which implicated glutamine as the principal precursor for neurotransmitter glutamate. PMID- 2876053 TI - Is dopamine-induced inhibition of adenylate cyclase involved in the autoreceptor mediated negative control of tyrosine hydroxylase in striatal dopaminergic terminals? AB - The mechanism of the negative control of tyrosine hydroxylase (TH) activity induced by the stimulation of presynaptic 3,4-dihydroxyphenylethylamine (dopamine, DA) autoreceptors was investigated using rat striatal slices and synaptosomes incubated under control ([ K+] = 4.8 mM) or depolarizing ([ K+] = 60 mM) conditions. The stimulation of DA autoreceptors by 7-hydroxy-2-(di-n propylamino)tetralin (1 microM 7-OH-DPAT) produced a significant decrease in TH activity extracted from striatal slices maintained under control conditions. This effect was associated with the complete conversion of TH into an enzyme form with a low affinity for its pterin cofactor (Km approximately 0.80 mM). Furthermore, compared to TH extracted from control tissues, that from 7-OH-DPAT-exposed striatal slices was more sensitive to the stimulatory effects of exogenous heparin and cyclic AMP-dependent phosphorylation. Such changes were opposite to those induced by incubating striatal slices with the adenylate cyclase activator forskolin. Indeed, forskolin treatment completely converted TH into an enzyme form with a high affinity for its pterin cofactor (Km approximately 0.16 mM). Such conversion was associated with a shift in the optimal pH for TH activity from 5.8 (control) to 7.2 (forskolin). Under depolarizing conditions, the blockade by (-)-sulpiride of the stimulation of DA autoreceptors by endogenous DA was associated with a marked activation of TH. Modifications of enzymatic characteristics triggered by (-)-sulpiride were then similar to those induced by forskolin treatment. These data suggest that presynaptic DA autoreceptors modulate the activity of TH by controlling the degree of cyclic AMP-dependent phosphorylation of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876054 TI - Binding sites for [3H]glutamate and [3H]aspartate in human cerebellum. AB - The binding of [3H]aspartate and [3H]glutamate to membranes prepared from frozen human cerebellar cortex was studied. The binding sites differed in their relative proportions, their inhibition by amino acids and analogues, and by the effects of cations. A proportion (about 30%) of [3H]glutamate binding was to sites similar to those labelled by [3H]aspartate. An additional component of [3H]glutamate binding (about 50%) was displaced by quisqualate and alpha-amino-3-hydroxy-5 methylisoxazole-4-propionic acid, and may represent a "quisqualate-preferring" receptor. Neither N-methyl-D-aspartic acid-sensitive nor DL-2-amino-4 phosphonobutyric acid-sensitive [3H]glutamate binding was detected. PMID- 2876055 TI - Specific insulin-mediated regulation of glutamine synthetase in cultured chick astroglial cells. AB - The expression of glutamine synthetase (GS; L-glutamate ammonia ligase; EC 6.3.1.2) in primary cultures of chick astroglial cells and neurons grown in a chemically defined medium, with and without insulin added, was investigated. An inhibitory effect of insulin toward GS activity, and specific to chick astroglial cells, was observed. Neurons in culture were not sensitive to the hormone effect. Modulation of the activating effect of hydrocortisone on glial GS by insulin was also observed. The data suggest that insulin contributes to the regulation of the metabolism of amino acid neurotransmitters via its effect on GS. PMID- 2876056 TI - Phorbol esters enhance neurotransmitter-stimulated cyclic AMP production in rat brain slices. AB - The effect of phorbol esters on cyclic AMP production in rat CNS tissue was examined. Using a prelabeling technique for measuring cyclic AMP accumulation in brain slices, it was found that phorbol 12-myristate, 13-acetate (PMA) enhanced the cyclic AMP response to forskolin and a variety of neurotransmitter receptor stimulants while having no effect on second messenger accumulation itself. A short (15-min) preincubation period with PMA was required to obtain maximal enhancement, whereas the augmentation was lessened by prolonged exposure (3 h) to the phorbol. The response to PMA was concentration dependent (EC50 = 1 microM) and regionally selective, being most apparent in forebrain, and was not influenced by removal of extracellular calcium or by inhibition of phosphodiesterase or phospholipase A2. Only those phorbols known to stimulate protein kinase C augmented the accumulation of cyclic AMP. Moreover, the membrane substrates phosphorylated by endogenous C kinase and by a partially purified preparation of this enzyme were similar. The results suggest that phorbol esters, by activating protein kinase C, modify the cyclic AMP response to brain neurotransmitter receptor stimulation in brain by influencing a component of the adenylate cyclase system beyond the transmitter recognition site. PMID- 2876057 TI - Glutamic acid as a putative transmitter of the interhemispheric corticocortical connections in the rat. AB - The effect of hemidecortication on the endogenous levels of amino acids in medial, sulcal, and dorsal frontal cortex as well as in parietal, temporal, and occipital cortex of the rat was investigated. Under aseptic conditions, the right cerebral cortex was aspirated by suction. Then, 21 days later, the content of glutamic acid, aspartic acid, gamma-aminobutyric acid, glycine, serine, threonine, and alanine was analyzed in six areas of the intact contralateral cortex using GLC. The results demonstrated a specific decrease in the endogenous levels of glutamic acid in both parietal and temporal cortex after hemidecortication of the contralateral side. This finding suggests that glutamic acid may serve as a neurotransmitter for some of the interhemispheric corticoparietal and corticotemporal fibers. In a follow-up experiment, the effect of a frontal lesion on the endogenous levels of the same amino acids in the striatum was also examined. In this case, the glutamic acid content exhibited a decrease of 31% relative to the control value. This observation confirms the earlier finding of a glutamate-containing pathway from the frontal cortex to the striatum. PMID- 2876058 TI - Perinatal hypoxia-ischemia disrupts striatal high-affinity [3H]glutamate uptake into synaptosomes. AB - We examined the impact of hypoxia-ischemia on high-affinity [3H]glutamate uptake into a synaptosomal fraction prepared from immature rat corpus striatum. In 7-day old pups the right carotid artery was ligated, and pups were exposed to 8% oxygen for 0, 0.5, 1, or 2.5 h, and allowed to recover for up to 24 h before they were killed. High-affinity glutamate uptakes in striatal synaptosomes derived from tissue ipsilateral and contralateral to ligation were compared. After 1 h of hypoxia plus ischemia, high-affinity glutamate uptake in the striatum was reduced by 54 +/- 13% compared with values from the opposite (nonischemic) side of the brain (p less than 0.01, t test versus ligates not exposed to hypoxia). There were similar declines after 2.5 h of hypoxia-ischemia. Activity remained low after a 1 h recovery period in room air, but after 24 h of recovery, high affinity glutamate uptake was equal bilaterally. Kinetic analysis revealed that loss of activity could be attributed primarily to a 40% reduction in the number of uptake sites. Hypoxia alone had no effect on high-affinity glutamate uptake although it reduced synaptosomal uptake of [3H]3,4-dihydroxyphenylethylamine. Addition of 1 mg/ml of bovine serum albumin to the incubation medium preferentially stimulated high-affinity glutamate uptake in hypoxic-ischemic brain compared with its effects in normal tissue. These studies demonstrate that hypoxia-ischemia reversibly inhibits high-affinity glutamate uptake and this occurs earlier than the time required to produce neuronal damage in the model. PMID- 2876059 TI - Hyperglycemia preserves brain mitochondrial respiration during anoxia. AB - We examined brain mitochondrial function in normo- (5 mM) and hyperglycemic (50 mM) cats after 8 min of anoxia. In anoxic normoglycemic cats, mitochondrial state 3 respiration with NAD-linked substrates glutamate or pyruvate (both plus malate) was inhibited 30-50%. The uncoupler carbonylcyanide p trifluoromethoxyphenylhydrazone (FCCP) maximally stimulated respiration, indicating that inhibition of phosphorylation, not impairment of electron transport, substrate transport, or oxidation was present. State 3 respiration with succinate (plus rotenone) was unaffected. Mitochondrial respiratory control ratios trended toward reductions whereas ADP/O ratios remained unchanged. In contrast, brain mitochondria from anoxic hyperglycemic cats showed no such inhibition of state 3 respiration and no differences in function from normo- and hyperglycemic control animals except for trends toward loose coupling. Significantly higher brain tissue glucose concentrations were present in hyperglycemic controls as the only metabolite difference compared to normoglycemic controls. At the end of anoxia, hyperglycemic cats exhibited significantly higher cortical lactate and glucose levels but similarly reduced high-energy phosphate concentrations compared to normoglycemic cats. These results demonstrate that increased availability of glucose to gray matter as a consequence of hyperglycemia maintains normal mitochondrial state 3 respiration during exposure to anoxia. Previous survival studies have shown that lower serum glucose concentrations during anoxia are relatively brain protective. This result indicates that the presently described alterations in mitochondrial respiration must be fully reversible. PMID- 2876060 TI - Effect of insulin-induced hypoglycemia on the concentrations of glutamate and related amino acids and energy metabolites in the intact and decorticated rat neostriatum. AB - The glutamate (Glu) terminals in rat neostriatum were removed by a unilateral frontal decortication. One to two weeks later the effects of insulin-induced hypoglycemia on the steady-state levels of amino acids [Glu, glutamine (Gln), aspartate (Asp), gamma-aminobutyric acid (GABA), taurine] and energy metabolites (glucose, glycogen, alpha-ketoglutarate, pyruvate, lactate, ATP, ADP, AMP, phosphocreatine) were examined in the intact and decorticated neostriatum from brains frozen in situ. The changes in the metabolite levels were examined during normoglycemia, hypoglycemia with burst-suppression (BS) EEG, after 5 and 30 min of hypoglycemic coma with isoelectric EEG, and 1 h of recovery following 30 min of isoelectric EEG. In normoglycemia Glu decreased and Gln and glycogen increased significantly on the decorticated side. During the BS period no significant differences in the measured compounds were noted between the two sides. After 5 min of isoelectric EEG Glu, Gln, GABA, and ATP levels were significantly lower and Asp higher on the intact than on the decorticated side. No differences between the two sides were found after 30 min of isoelectric EEG. After 1 h of recovery from 30 min of isoelectric EEG Glu, Gln, and glycogen had not reached their control levels. Glu was significantly lower, and Gln and glycogen higher on the decorticated side. The Asp and GABA levels were not significantly different from control levels. The results indicate that the turnover of Glu is higher in the intact than in decorticated neostriatum during profound hypoglycemia. PMID- 2876061 TI - Neuropeptides in gliomas: identification of somatostatin 14 in a medulloblastoma. AB - Forty nine gliomas were analysed for the following neuropeptides: somatostatin (SS), substance P (SP), neurotensin (NT) and vasoactive intestinal polypeptide (VIP) and the pituitary peptide, adrenocorticotrophin (ACTH). A significant amount of authentic SS was found in a medulloblastoma, and low concentrations of SP and NT immunoreactivity in an ependymoma and cerebellar astrocytoma respectively. The majority of the other gliomas did not contain detectable levels of these five neuropeptides. Low levels of neuropeptides were found in some specimens probably due to contamination with cerebral cortex. PMID- 2876062 TI - Rationale for the choice of antihypertensive agents. PMID- 2876063 TI - The contribution of GABA-mediated inhibitory mechanisms to visual response properties of neurons in the kitten's striate cortex. AB - The effect of the microiontophoretic administration of the GABA antagonist bicuculline methiodide (BMI) on the responses of striate cortical neurons to light stimulation was investigated in kittens ranging in age between 11 and 28 d. The orientation sensitivity of the majority of the 88 neurons tested for this parameter decreased (40%) or was eliminated (18%) following the administration of BMI. Changes were seen in all layers and in all neuronal types, and the proportions of neurons that changed their orientation specificity were about the same during the second, third, and fourth postnatal weeks. Twenty-eight percent of the neurons were not affected in their orientation sensitivity by BMI. These neurons were recorded at all postnatal ages; they were located preferentially in layers IV and VI; and they had unimodal, bimodal, or ON-OFF mixed receptive fields. The remaining 14% of the neurons were initially unresponsive or responded in an erratic way to visual stimulation. These neurons became responsive and even exhibited orientation-specific responses during administration of BMI. The majority (56%) of direction-specific neurons became direction-nonspecific after the administration of BMI. Seventeen percent preserved some direction specificity, whereas 27% did not show any change at all. The effects of BMI on direction sensitivity were seen at all postnatal ages and on all neuronal types throughout layers III-VI. The majority of neurons unaffected by BMI in their direction sensitivity resided in layer VI. In those cases where orientation sensitivity was reduced, direction sensitivity (if present) was usually diminished as well. However, some neurons were found in which only 1 of the 2 parameters was significantly changed by BMI. The spatial structure of the receptive field, as revealed by stationary stimulation, was changed significantly by BMI in about half the neurons tested. A straightforward correlation between the alteration of orientation and/or direction sensitivity and changes in receptive-field structure was not found. The results demonstrate that, in the immature striate cortex, receptive-field properties of many neurons are determined by inhibitory processes mediated by GABA, which may also dictate the actual visual responsiveness of the neurons. The dissociations in the effects of BMI on orientation sensitivity, direction sensitivity, and receptive-field substructure indicate that the synaptic organization responsible for the various functional parameters is unlikely to be the same. PMID- 2876064 TI - Evidence for GABA as a neurotransmitter in the leech. AB - In the leech, Hirudo medicinalis, the inhibitory motor neurons to the longitudinal muscles in the body wall, cells 1 and 2, are linked via central inhibitory synapses to the excitatory motor neurons innervating the same muscles. Examination of these synapses showed that the inhibitors are GABAergic according to several electrophysiological and pharmacological criteria. Presynaptic release of neurotransmitter during passage of depolarizing current into the inhibitors, as well as direct application of GABA to the excitor cell bodies, hyperpolarizes the postsynaptic excitor. Moreover, both synaptic and extrasynaptic GABA receptors of the excitors are specifically blocked by the GABA antagonist bicuculline methiodide. The inhibitors, dissected from the ganglion and grown in culture, synthesize GABA when exposed to the GABA precursor glutamate, whereas the excitors do not synthesize detectable levels of GABA under these same conditions. The innervation and neurotransmitter sensitivity of the longitudinal muscles in the body wall of the glossiphoniid leeches Haementeria ghilianii and H. officinalis were examined in order to determine if the inhibitory neurotransmitter at the neuromuscular junction is GABA. Individual muscle fibers are innervated by both inhibitory and excitatory motor neurons in a manner such that the inhibitory and excitatory nerve terminals and neurotransmitter receptors are spatially and electrically separate. Intracellular recordings taken from the muscle fibers reveal a resting potential of about -70 mV. The amplitude of the spontaneous inhibitory junctional potentials (IJPs) falls to zero at a polarization of about -65 mV and reverses in sign at the normal resting potential.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876065 TI - Sustained transmitter output by increased transmitter turnover in limb muscles of old mice. AB - The ability of neuromuscular junctions in old animals to maintain tetanic output was tested in phasic and tonic limb muscles and the physiologic mechanism of maintenance was elucidated by analysis of the turnover of a false transmitter during prolonged tetani. Transmitter release during and after tetani was compared in limb muscles of young (8-9 month) and old (28-30 month) male CBF-1 mice. Amplitudes of end-plate potentials (epp's) in curarized preparations and of spontaneous miniature end-plate potentials (mepp's) were measured in vitro at 30 degrees C in soleus and extensor digitorum longus (edl) muscles. In both young and old soleus muscles, epp amplitude was maintained at about 45% of resting level during the latter part of trains of 1,200 stimuli at 10 Hz but recovered to about 90% control within a few seconds after stimulation ceased. In edl muscles of young mice, epp amplitudes during a 20 Hz train of 1,200 impulses steadily declined to about 20% of control and gradually recovered over 2 min after the tetanus. In old edl muscles, tetanic decay of the epp's was greater and recovery slower than in young muscles, but absolute epp amplitudes were invariably greater. During trains of 6,000 impulses at 10 Hz, plateau epp amplitude decayed to 40-50% in young soleus muscle and 30-40% control in old muscle, but recovery was similar and absolute epp amplitudes were greater in old soleus muscle. A false transmitter precursor, homocholine (HoCh), was used to investigate the mechanism of this prolonged output, and, therefore, the use of HoCh in this system was first validated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876066 TI - Brain-derived neurotrophic factor supports the survival of cultured rat retinal ganglion cells. AB - Brain-derived neurotrophic factor (BDNF) is a small, basic protein purified from the mammalian brain that has been shown previously to support the survival of cultured spinal sensory neurons (Barde et al., 1982). In current studies, BDNF was tested for its ability to support the survival of cultured CNS cells isolated from the perinatal rat retina. Both immunofluorescent labeling of Thy-1 and prior retrograde labeling with HRP were used as retinal ganglion cell markers in vitro. With embryonic day (E) 17 retinas, it was found that BDNF allowed the survival of a small subpopulation of neurons (about 7% of the cells plated at this age) identified by the immunofluorescent labeling of Thy-1. No detectable effects were seen when either the total number of cells or the number of tetanus toxin positive neurons was measured. BDNF also had an effect on cultured neurons retrogradely labeled after HRP injections in the superior colliculi of neonatal rats. The BDNF-responsive population was therefore detected only in retinal cultures with specific markers and identified as consisting of retinal ganglion cells. These cells could be enriched about 80-fold by density gradient centrifugation, and purified ganglion cell cultures were shown to be responsive to BDNF. Whereas with E17 retinas, the number of surviving Thy-1 positive neurons could be kept constant for at least 4 d, the survival of postnatal neurons was only transiently increased by BDNF. We conclude that in the retina, BDNF affects only the survival of ganglion cells in vitro by a direct action on these cells. The results are discussed in terms of target-derived neurotrophic support during development. PMID- 2876067 TI - Kainic acid alters the metabolism of Met5-enkephalin and the level of dynorphin A in the rat hippocampus. AB - Male Fischer-344 rats were given a single intrastriatal injection of kainic acid (KA; 1 microgram/rat), which caused recurrent motor seizures lasting 3-6 hr. During the convulsive period, native Met5-enkephalin-like (ME-LI) and dynorphin A (1-8)-like (DYN-LI) immunoreactivities in hippocampus decreased by 31 and 63%, respectively. By 24 hr after dosing, the hippocampal opioid peptides had returned to control levels, and by 48 hr ME-LI had increased 270% and DYN-LI 150%. Immunocytochemical analysis revealed that ME-LI and Leu5-enkephalin-like (LE-LI) immunostaining in the mossy fibers of dentate granule cells and the perforant temporoammonic pathway had decreased visibly by 6 hr and had increased markedly by 48 hr following KA. A visible decrease in DYN-LI in mossy fiber axons within 6 hr was followed by a substantial increase by 48 hr. To determine whether the increases in hippocampal ME-LI reflected changes in ME biosynthesis, levels of mRNA coding for preproenkephalin (mRNAenk) and cryptic ME-LI cleaved by enzyme digestion from preproenkephalin were measured. Following the convulsive period (6 hr), mRNAenk was 400% of control, and by 24 hr, cryptic ME-LI was 300% of control. Increases in native and cryptic ME-LI and in mRNAenk were also noted in entorhinal cortex, but not in hypothalamus or uninjected striatum. Our data suggest that KA-induced seizures cause an increase in ME release, followed by a compensatory increase in ME biosynthesis in the hippocampus and entorhinal cortex. PMID- 2876068 TI - Inhibition of liver lipogenesis by dietary polyunsaturated fat in severely diabetic rats. AB - Diabetic and nondiabetic rats were used to ascertain if dietary polyunsaturated fats inhibited hepatic acetyl-CoA carboxylase and fatty acid synthetase in insulin-insufficient rats as had been previously shown for normal rats. Male rats were rendered diabetic (400-600) mg glucose/100 mL blood) with streptozotocin and were fed a high fructose fat-free diet. Safflower oil or palmitate (or tallow) was added to the basal fructose diet at a level to supply 12,24 or 36% additional digestible energy. Compared with normal rats, diabetic rats had significantly lower hepatic fatty acid biosynthesis, but the proportion of acetyl-CoA carboxylase expressing catalytic activity as determined by the avidin inactivation technique was unaffected by diabetes. Diabetes did not lower the maximal maximal activities of carboxylase and fatty acid synthetase. Moreover, the activities of these enzymes greatly exceeded the rate of fatty acid synthesis. At all levels of fat supplementation, the high linoleate safflower oil consistently resulted in a 50% lower rate of fatty acid biosynthesis than did comparable levels of tallow or palmitate. Safflower oil was also a more effective suppressor of the activities of acetyl-CoA carboxylase and fatty acid synthetase than the saturated fats. Our data suggest that the greater inhibition of hepatic fatty acid biosynthesis by polyenoic fatty acids is an insulin-independent mechanism. PMID- 2876069 TI - Determination of L-ascorbic acid in tomato by isotachoelectrophoresis. Application of computer simulation system for setting of determination conditions to avoid the mixed-zone problem. AB - When the isotachoelectrophoretical method is used with HCl-beta-alanine as the leading electrolyte solution (pH 3.6), ascorbic acid forms a mixed zone with glutamic acid, and it is difficult to separate the two. Therefore, the application of a computer simulation system to separate the two acids was investigated. This system can be used with compounds for which the absolute electrophoretical mobility and dissociation constant have already been determined. Values for glutamic acid alone were entered in the data bank "SIPS 1", and then those for ascorbic acid were estimated from the values of similar compounds. Values for aspartic acid were used, and the electrophoretical behavior of ascorbic and glutamic acids was simulated at pH range from 3 to 9.9. Based on this simulation, separation appeared possible at pH 9.0 to 10.0, and indeed, experimental determination of ascorbic acid was successfully performed with a leading electrolyte solution composed of HCl-ethanolamine (pH 9.4) without any glutamic acid interference. Even though ascorbic acid is highly susceptible to oxidation in an alkaline medium, because the ascorbic acid solution is injected at the interface of the leading and terminal electrolyte solutions in the electrophoretical procedure, it does not come in contact with air during electrophoresis. This explains why ascorbic acid can be determined in an alkaline medium. PMID- 2876070 TI - Properties of amiodarone monolayer spread at the air-water interface. AB - Surface pressure measurements demonstrate that, over a wide range of pH, amiodarone forms a stable monolayer at the air-water interface. The area found to be occupied by an amiodarone molecule was compared with a theoretical prediction based on a conformational analysis, making it possible to assemble amphiphilic molecules. The intrinsic ionization constant of amiodarone in an aqueous environment pKi = 8.7 +/- 0.5 was evaluated from surface potential measurements. PMID- 2876071 TI - The effect of the relationship between punch velocity and particle size on the compaction behaviour of materials with varying deformation mechanisms. AB - The effect of punch velocity over the range 0.033-300 mm s-1 on the compaction properties of lactose, microcrystalline cellulose and a drug substance (a phthalazine derivative) for a range of particle sizes has been studied using the yield pressure derived from the Heckel relationship and a strain rate sensitivity index (SRS index), as the criteria to describe their behaviour. For lactose, a material which deforms by a mixed mechanism of particle fracture and plastic deformation at the contact points, the yield pressure increased and the SRS index decreased as particle size decreased, due to a reduction in the amount of fragmentation of the particles. For microcrystalline cellulose, a material which is known to deform plastically, the yield pressure and the SRS index were independent of particle size. For the phthalazine derivative the yield pressure increased as particle size decreased; however the SRS index reduced from 41% to zero, indicating that the deformation mechanism was changing from plastic flow to brittle behaviour. This decrease in the SRS index has been explained in terms of the relative amounts of strain-hardened material produced as milling severity increased, resulting in an increasing resistance to deformation and thus an apparent increase in brittle behaviour as particle size decreased. PMID- 2876072 TI - Comparison of fluorescence polarization immunoassay and high performance liquid chromatography for the quantitative determination of phenytoin, phenobarbitone and carbamazepine in serum. AB - The Abbott TDx fluorescence polarization immunoassay (FPIA) system has been evaluated and compared with well-established high performance liquid chromatography (HPLC) for the determination of three anticonvulsant drugs: phenytoin, phenobarbitone and carbamazepine. These assays were evaluated for precision, calibration curve stability, specificity and accuracy. Within-run precision studies using control samples (n = 15) in the subtherapeutic, therapeutic, and toxic concentrations, resulted in coefficients of variation in the range of 1.79-3.99% (FPIA) and 1.16-2.52% (HPLC), respectively. Between-run precision ranged from 2.32-6.34% for FPIA and from 2.04-3.38% for HPLC. Comparison of 122 patient samples assayed with both methods indicated an extremely good analytical correlation (r = 0.96) for all three comparisons. The FPIA method offers significant advantages in calibration curve stability while maintaining accuracy and precision comparable with those of established HPLC procedures. PMID- 2876073 TI - Plasma concentrations and pharmacokinetics of midazolam during anaesthesia. AB - Midazolam and 1-hydroxymidazolam plasma concentrations have been monitored and pharmacokinetic parameters of midazolam estimated during anaesthesia induced and maintained by its repeated injection according to two protocols (3 X 0.3 mg kg-1 at 45 min intervals or an induction dose of 0.3 mg kg-1 with maintenance doses of 0.15 mg kg-1 at 30 min intervals). Minimum plasma concentrations of midazolam measured just before each injection were 258.8 +/- 108.4 ng ml-1 for the first protocol and 353.1 +/- 55.2 ng ml-1 for the second protocol; maximum midazolam concentrations, measured 5 min after the last administration, were 1103.1 +/- 237.9 ng ml-1 and 743.0 +/- 103.2 ng ml-1, respectively, suggesting that a continuous infusion of midazolam after a loading dose should be better than repeated injections at keeping the concentration close to the sedative level of 400 ng ml-1. The estimated pharmacokinetic parameters were similar to those already published, except for the beta elimination half-life of midazolam (3.24 +/- 0.90 h for protocol 1 and 3.34 +/- 1.47 h for protocol 2) which was slightly longer than that reported for single dose studies. The comparison of plasma determinations, obtained either by gas-liquid chromatography or by a radioreceptor assay technique, clearly showed that 1-hydroxymidazolam, even after repeated midazolam administration, was not present at a concentration sufficient to affect the overall pharmacological activity of the parent drug. PMID- 2876074 TI - Interaction of cyclosporin A with human lipoproteins. AB - The ultracentrifugal fractionation of human serum after previous incubation with cyclosporin A showed that, in healthy fasting individuals, 8% of cyclosporin A was found in the very low density lipoproteins (VLDL), 31% in the low density lipoproteins (LDL), 46% in the high density lipoproteins (HDL) and 15% in the non lipoprotein protein fraction. In non-fasted, healthy and in non-fasted, lipaemic individuals, 7 and 6% of cyclosporin A was found in chylomicrons, 9 and 13% in VLDL, 28 and 30% in LDL, 39 and 37% in HDL, and 12 and 13% in the non-lipoprotein protein fraction, respectively. In patients receiving cyclosporin A the distribution varied from 12 to 19% in VLDL, 21 to 28% in LDL, 33 to 43% in HDL, and 13 to 20% in non-lipoprotein proteins. The interaction between cyclosporin A and isolated normal human lipoproteins was also studied by ultrafiltration. All lipoproteins exhibited a non-saturable, low affinity, high capacity uptake for cyclosporin A. Analysis of the uptake by phospholipid vesicles showed a similar uptake, suggesting that cyclosporin A dissolves in the lipophilic portion of the lipoprotein molecule rather than being associated with specific binding sites. PMID- 2876075 TI - The effects of new local anti-inflammatory steroids on leucocyte migration and prostanoid liberation in rats. AB - The local anti-inflammatory potency of steroid-21-oate esters derived from prednisolone was determined by cotton pellet granuloma bioassay. The doses which inhibited granuloma formation by 50% (ID50) were: prednisolone, 0.5 mg/pellet; methyl 20 alpha-dihydroprednisolonate, 5.8 mg/pellet; methyl 20 beta dihydroprednisolonate, 1.2 mg/pellet; methyl 17,20 alpha acetonidodihydroprednisolonate, 6.0 mg/pellet. When administered at these equipotent local anti-inflammatory doses, only prednisolone depressed plasma corticosterone and promoted thymus involution. Prednisolone reduced neutrophil migration into saline-soaked polyester sponges and depressed the levels of 6-keto PGF1 alpha, PGE2 and elastase in the sponge-induced inflammatory exudate. Methyl 20 alpha- and 20 beta-dihydroprednisolonate had no effect on cell migration, but depressed the levels of 6-keto PGF1 alpha and elastase. The liberation of 6-keto PGF1 alpha, PGE2 and elastase and neutrophil migration were inhibited by methyl 17,20 alpha- and beta-acetonidodihydroprednisolonate, but the effect of the beta epimer on cell migration was transient. These data suggest that steroid acid esters which have local and topical anti-inflammatory properties exert their effect in a similar fashion to glucocorticoids with a ketol side-chain (e.g. prednisolone) with respect to liberation of prostaglandins and lysosomal enzymes. However, their effect on neutrophil migration was variable, depending on their structural features. Furthermore, the systemic effects of these new derivatives were drastically reduced indicating that they may be of potential benefit in prolonged treatment. PMID- 2876077 TI - Dual effect of orally administered sennosides on large intestine transit and fluid absorption in the rat. AB - Quantity and consistency of the faecal output, large intestine transit time, and colonic net fluid absorption were investigated in rats after oral administration of sennosides A + B (12.5-200 mg kg-1). The release of normal faecal pellets was accelerated 3-4 h after drug administration; excretion of soft faeces was evident within 4-5 h and reached its maximum 5-7 h after administration. Large intestine transit time was dose- and time-dependently influenced by sennoside treatment. A highly significant reduction in transit time from more than 6 h in controls to 90 min for a 2 h pretreatment and a nearly maximal reduction to 30 min for a 4 h pretreatment was induced by a dose of 50 mg kg-1. Inhibition of net fluid absorption in the colon was maximal with the same dose, but clearly more pronounced after a 6 h pretreatment period than after a 4 h period. Since the increase in fluid volume due to net fluid secretion is delayed compared with the acceleration of large intestine transit, the early motility effect seems to be largely independent of the changes in absorption mechanisms. Therefore, the laxative effect of the sennosides consists of changes in colon motility as well as in colonic fluid absorption, but motility may be an earlier and more sensitive parameter than net absorption. PMID- 2876076 TI - Pharmacological characterization of the postsynaptic alpha-adrenoceptors in human uterine artery. AB - Prazosin and yohimbine were used to differentiate postjunctional alpha adrenoceptors in the human uterine artery in-vitro. Two postjunctional alpha adrenoceptor subtypes were distinguished by the affinities of the receptor for yohimbine and prazosin. The pA2 for prazosin was 8.91 against phenylephrine with a slope not significantly different from unity (0.91), and the pA2 for yohimbine was 7.25 against naphazoline and 8.70 against clonidine, with slopes not significantly different from unity (1.11 and 1.18, respectively). Yohimbine was not very active against phenylephrine, while prazosin was very active against the mixed and selective alpha 2-adrenoceptor agonist noradrenaline and clonidine; the intercepts of the Schild plot were 8.80 and 8.82 but with slopes significantly less than unity (0.77 and 0.67, respectively). Prazosin competitively antagonized phenylephrine at the alpha 1-adrenoceptor, whereas yohimbine competitively antagonized naphazoline and clonidine at the alpha 2-adrenoceptor. It is concluded that both alpha 1- and alpha 2-adrenoceptors are present in the human uterine artery. PMID- 2876078 TI - Racemic and optically active trans 2,6-dimethyl analogues of the reversed ester of pethidine. AB - The preparation and stereochemical characterization of (+/-)-1,trans 2,6 trimethyl-4-phenyl-4-propionoxypiperidine hydrochloride and its (+)- and (-) antipodes are described. The absolute configurations of the antipodes were established by X-ray analysis of the corresponding (-)-4-piperidinol hydrobromide. In antinociceptive tests on mice and rats, the (+)-2S,6S ester proved the more potent antipode by factors of at least 10 (rats) and 20 (mice), a result consistent with earlier proposals made about the probable uptake conformation of pethidine reversed esters at opioid receptors. PMID- 2876079 TI - Fast-atom bombardment mass spectra of some pentapeptides related to natural enkephalins. AB - The mass spectral features of four diastereoisomeric pairs of peptides related to the enkephalins recorded under fast-atom bombardment conditions are presented and shown to provide evidence of molecular weight and amino acid content and sequence. PMID- 2876080 TI - Some pharmacokinetic characteristics of furafylline, a new 1,3,8-trisubstituted xanthine. AB - After administration of furafylline, a, 1,3,8-trisubstituted xanthine, to beagle dogs at 0.5 and 10 mg kg-1 an elimination half-life 2-10 times longer than that of theophylline was observed. The kinetics were dose-dependent but no phase I metabolites were detected. When the compound was given orally to humans at a dose of 1.3-1.9 mg kg-1 a mean beta elimination half-life of 48.1 +/- 10.8 h was obtained after an initial distribution phase. Evidence of non-linear kinetics for plasma levels below 0.6 microgram ml-1 was also obtained. Other 1,3,8 trisubstituted xanthines, may also have a lower elimination rate than theophylline. PMID- 2876081 TI - Antitumour effect of fibrinogen microspheres containing doxorubicin on Ehrlich ascites carcinoma. AB - The antitumour activity of fibrinogen microspheres containing doxorubicin has been evaluated against Ehrlich ascites carcinoma in mice in terms of changes in body weight and survival. Tumour cell injections were made on day 0 and microsphere injections on day 1, both intraperitoneally. The suppressive effect of the drug-containing microspheres on increase in body weight was higher than that of the free drug, and tumour-bearing mice given the microspheres lived longer than those given the free drug. PMID- 2876082 TI - Neither morphine nor clonidine influence the non-adrenergic, non-cholinergic inhibitory response in the rat gastric fundus. AB - Morphine and clonidine are among the few agents reported to modulate non adrenergic, non-cholinergic (NANC) responses in different tissues. They were therefore tested for their effect on the NANC inhibitory response in the rat gastric fundus. Neither morphine (10(-5) M), nor clonidine (10(-5) M in the presence of prazosin 10(-6) M to avoid its own relaxatory effect) modified the NANC response in the rat gastric fundus. PMID- 2876083 TI - Differing potencies of muscle relaxants on rat and guinea-pig phrenic nerve diaphragm preparations. AB - The sensitivities of two in-vitro preparations to neuromuscular blocking agents have been compared. The guinea-pig phrenic nerve diaphragm preparation proved to be more sensitive to vecuronium, atracurium and pancuronium than the equivalent preparation from the rat. Only tubocurarine had a similar potency on the preparations from both species. This would suggest that the guinea-pig diaphragm would be the most appropriate bioassay preparation if only small quantities of drug were available. Small differences in the cholinesterase content of the preparations was not thought to be a likely reason for the differences between the two preparations. PMID- 2876084 TI - Effects of diltiazem on morphine-induced respiratory decline. AB - The individual and combined effects of subcutaneous morphine and diltiazem, a calcium channel inhibitor, on arterial blood gases and pH were assessed in conscious Fischer-344 rats. Morphine (4 mg kg-1) produced hypercapnia, hypoxia and slight acidosis, as compared with control values. Diltiazem (10 mg kg-1) alone did not affect these parameters; however, it significantly delayed the onset of the aforementioned effects of morphine. PMID- 2876085 TI - Laxatives and the production of autacoids by rat colon. AB - The effects of some laxatives were examined on the formation of histamine, 5 hydroxytryptamine (5-HT) and prostaglandin-like material (PG-LM) by rat intestine in-vitro. Castor oil, senna, sulphosuccinate and bisacodyl, but not mannitol or lactulose, in doses that cause laxation, increased the formation of histamine, 5 HT and PG-LM. Indomethacin or hydrocortisone reduced the increase of PG-LM formation. The data support the idea that the laxative effects of these intestinal secretagogues are due to increased intestinal production of PG-LM, histamine and 5-HT. PMID- 2876086 TI - Spectrofluorimetric analysis and buccal absorption of medifoxamine. AB - Medifoxamine is a new investigational antidepressant drug. Its buccal absorption at pH 5-9, which can be considered as an in-vivo model of passive drug transfer through a lipid membrane, was studied in six normal, healthy volunteers to predict its pharmacokinetic profile in man. Maximum absorption of medifoxamine occurred at pH 8, which is close to its pKa (8.5). PMID- 2876087 TI - The effect of proadifen on the metabolism of adinazolam. AB - Binding affinities of adinazolam and its metabolite mono-N-demethyladinazolam, U 42352, to the brain tissue are not altered by the presence of proadifen (SKF 525A) in [3H]flunitrazepam [( 3H]FNZ) binding assays in-vitro. Pretreatment of mice with proadifen significantly blocked the ability of intravenously administered adinazolam to inhibit [3H]FNZ binding in the studies ex-vivo. The binding profile of [3H]FNZ to the brain tissue was not significantly different when animals were treated with U-42352 or proadifen with U-42352. These results suggest that proadifen may block the conversion of adinazolam to its active metabolite U-42352. PMID- 2876088 TI - [Stereoselective glucuronidation of beta-blocking agents, 1-tert-butylamino-3 (2,3-dimethylphenoxy)-2-propanol (D-32) and propranolol, in animals, in vivo and in vitro]. PMID- 2876089 TI - In vitro characterization of the adrenoceptor activity of AY-28,925. AB - The adrenoceptor activity of AY-28,925 (5-[1-hydroxy-2-[(1-methyl-3 phenylpropyl)amino]ethyl]-1 H-indole-7-carboxamide) was evaluated on various isolated vascular and nonvascular tissues. Based upon pA2 values derived from either the antagonism of the effect of isoproterenol on paced guinea pig left atria (pA2 = 7.3), spontaneously beating guinea pig right atria (pA2 = 7.4) or canine saphenous vein (pA2 = 7.3), AY-28,925 demonstrated nonselective beta adrenoceptor antagonist activity. Studies using the spontaneously beating guinea pig right atria and the prostaglandin F2 alpha-contracted canine saphenous vein indicated that AY-28,925 also possessed nonselective beta-adrenoceptor intrinsic efficacy. AY-28,925 was shown to be a selective alpha-1 adrenoceptor antagonist with a pA2 value which was greater against phenylephrine in the rabbit aorta (pA2 = 6.6) than against clonidine in the rat vas deferens (pA2 = 5.4) or B-HT 920 in the canine saphenous vein (pA2 = 5.3). Only in concentrations greater than 2000 times those required for adrenergic activity was AY-28,925 able to inhibit potassium chloride- or prostaglandin F2 alpha-induced contractions of the rabbit aorta. The compound had no significant negative intropic activity. These experiments indicate that AY-28,925 possesses, in decreasing orders of activity: nonselective beta-adrenoceptor properties; a selective alpha-1 adrenoceptor inhibitory effect; and a nonspecific direct relaxing action on vascular smooth muscle. PMID- 2876090 TI - Some behavioral effects of histamine H1 antagonists in squirrel monkeys. AB - Graded dose of the histamine H1 antagonists tripelennamine (0.1-3.0 mg/kg), promethazine (0.1-3.0 mg/kg), diphenhydramine (0.3-10.0 mg/kg) and chlorpheniramine (0.3-1.7 mg/kg) increased rates of nonsuppressed responding under a second-order schedule of food presentation to a maximum beyond which responding was increased less or decreased. In contrast, the H2 antagonist, cimetidine, had no effect or decreased responding at the highest doses studied (56.0-100.0 mg/kg). Intermediate doses of tripelennamine, diphenhydramine and promethazine also increased rates of food-maintained responding that were suppressed by electric shock. Maximal increases in rates of suppressed responding were comparable to those produced by effective doses of chlordiazepoxide (3.0 10.0 mg/kg). Under identical conditions, clozapine (0.1-1.0 mg/kg) increased responding to a lesser extent, and d-amphetamine (0.01-0.3 mg/kg) and cimetidine (3.0-100.0 mg/kg) either did not increase or, at the highest doses, only decreased rates of suppressed responding. Doses of tripelennamine and diphenhydramine that increased rates of nonsuppressed and suppressed responding also maintained self-administration in cocaine-trained squirrel monkeys under a second-order schedule of i.v. injection. Rates and patterns of responding maintained by tripelennamine and diphenhydramine were comparable to those maintained by cocaine and d-amphetamine under identical conditions. The results show that histamine H1 antagonists can have pronounced rate-increasing effects on nonsuppressed and suppressed behavior, and that they can serve as reinforcers in monkeys. These effects occur at doses that probably are greater than those required to saturate H1 sites of action in central nervous system and may not be mediated solely through histaminic mechanisms. PMID- 2876091 TI - Effects of BMY 14802, a potential antipsychotic drug, on rat brain dopaminergic function. AB - The potential neuroleptic alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1 piperazine-butanol HCl (BMY 14802-1) was tested for its effects on mesotelencephalic dopamine (DA) neurons in albino rats. BMY 14802-1 increased DA turnover in DA terminal regions, increased nigral DA neuronal impulse flow and blocked the behavioral stimulation and inhibition of DA neuronal impulse flow caused by DA agonists. BMY 14802-1 also increased tyrosine hydroxylase activity in vivo but did not directly affect tyrosine hydroxylase activity in vitro. In contrast to these findings, BMY 14802-1 did not cause catalepsy at any dose and reversed catalepsy produced by haloperidol. BMY 14802-1 did not block DA autoreceptors on either DA neuron soma/dendrites or on striatal nerve terminals, as assessed by inhibition of DA neuronal impulse flow by microiontophoresed DA and by inhibition of tyrosine hydroxylase activity by apomorphine, respectively. BMY 14802-1 had very low affinity for striatal D-2 receptors (IC50 greater than 10(-5) M) as determined by displacement of [3H]spiperone binding in vitro. Finally, BMY 14802-1 increased impulse flow of nigral DA neurons after pretreatment with haloperidol but had no effect on impulse flow when microiontophoresed directly onto DA neurons. It is concluded that BMY 14802-1 blocked DA-mediated effects in the mesostriatal and mesocortical/limbic systems through a non-DA receptor mechanism. BMY 14802-1 has potential as a neuroleptic with little indication of extrapyramidal motor effects. PMID- 2876092 TI - Kinetic analysis of the interactions of agonists and antagonists with beta adrenergic receptors. AB - The affinity of the beta adrenergic receptor for antagonists is frequently higher than that for agonists. It has been assumed that the binding of agonists and antagonists is diffusion limited and that the high affinity of the receptor for typical antagonists is due to slow rates of dissociation. To test this hypothesis, the kinetics of binding of unlabeled agonists and antagonists were determined using the method described by Motulsky and Mahan (Mol. Pharmacol. 25: 1-9, 1984). The time course of the binding of a radioligand in the presence of a competing unlabeled ligand was analyzed in terms of rate constants of association (kon) and dissociation (koff) for binding of the radioligand and the competitor. This approach was validated by showing that the rate constants for binding of [3H]dihydroalprenolol and [3H]CGP-12177 [[3H]-4-(3-tertiarybutylamino-2 hydroxypropoxy)-benzimidazole-2-on ] determined directly were similar to values determined when the binding of [125I]iodopindolol was measured in the presence of [3H]dihydroalprenolol or [3H]CGP-12177. Computer simulations suggested that this method was experimentally limited to competing ligands with rate constants of dissociation below approximately 0.50 min-1. The apparent rate constants for binding of four unlabeled agonists and eight antagonists were determined experimentally at 10 degrees C. Although the values of koff for agonists and antagonists were similar, the values for kon for binding of agonists were consistently lower than the values for binding of antagonists. The relatively slow rate constant for association of agonists may be explained by a two-step mechanism or may involve agonist-induced isomerization of the receptor. PMID- 2876093 TI - Organophosphate and carbamate compounds have pre- and postjunctional effects at the insect glutamatergic synapse. AB - The effects of the organophosphate compounds diisopropylfluorophosphate (DFP), dimethylphosphoramidocyanidic acid ethyl ester (tabun), O-ethyl S-2 diisopropylaminoethyl-methyl phosphonothiolate (VX) and the carbamate compound 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indol-5-ol methylcarbamate (physostigmine) were studied on the metathoracic flexor and extensor tibialis muscles of Locusta migratoria. These anticholinesterase (anti-ChE) agents interacted with pre- and post-synaptic regions of the glutamatergic neuromuscular synapse. In physiological solution, containing normal calcium concentration (2 mM), these agents initiated spontaneous excitatory post-synaptic potentials (EPSPs) and muscle action potentials (APs) alternating with periods of reduced spontaneous activity in which only miniature excitatory postsynaptic potentials (MEPSPs) could be recorded. This spontaneous EPSP and AP firing was influenced by [Ca++]0; at low concentrations, the spontaneous APs were abolished but EPSPs and MEPSPs could still be seen. Further reduction of [Ca++]0 to 0.2 mM abolished EPSP firing and only MEPSPs were recorded. This spontaneous activity, EPSP and AP, was blocked by tetrodotoxin (0.3 microM). Neither nicotinic nor muscarinic antagonists were able to abolish the presynaptic action of these agents. In addition to these presynaptic actions, a decrease of the peak amplitude of the excitatory postsynaptic currents (EPSC) was induced by perfusion with DFP, VX or physostigmine. Only DFP and VX affected the decay time constant of the EPSC. Furthermore, high concentrations of tabun did not affect the EPSP. Both the pre- and postsynaptic effects of these agents were reversible upon washing the preparations. The present results demonstrate a new site of action of these compounds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876094 TI - Ablation of the myenteric plexus impairs alpha but not beta adrenergic receptor mediated mechanical responses of rat jejunal longitudinal muscle. AB - The mechanical responses produced by alpha and beta adrenergic receptor agonists were evaluated in control and myenteric neuron-ablated rat jejunal longitudinal muscle. The myenteric plexus of the jejunum was destroyed by serosal application of benzalkonium chloride (BAC). The beta adrenergic receptor agonists isoproterenol and sulfonterol produced a concentration-dependent relaxation of both control and BAC-treated jejunum. Dose-response curves obtained in control and BAC-treated jejunum were nearly superimposable regardless of the beta agonist used. Isoproterenol-induced relaxation was antagonized by the beta receptor antagonists propranolol and practolol but not by butoxamine. The alpha-1 selective agonists phenylephrine and methoxamine were more potent and efficacious in producing relaxation of control than BAC-treated jejunum. The relaxant responses of methoxamine and phenylephrine in control jejunum were blocked by prazosin but not by yohimbine. The supposed alpha-2 selective agonist clonidine also produced a concentration-dependent, prazosin-sensitive, yohimbine-resistant relaxation which was markedly greater in control than BAC-treated jejunum, consistent with alpha-1 receptor stimulation. Clonidine tested in the presence of prazosin and the alpha-2 selective receptor agonists UK-14,304, M-7 and B-HT 920 all produced a concentration-dependent contraction of control but not BAC-treated jejunum. The contractile response produced by UK-14,304 was antagonized by yohimbine but not by atropine. Our results suggest that in rat jejunal longitudinal muscle: beta adrenergic receptors mediate relaxation and are located on the smooth muscle; alpha-1 adrenergic receptors mediate relaxation and are located on both the smooth muscle and myenteric plexus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876095 TI - Inlay repair of a broken solder joint. PMID- 2876097 TI - Neuroleptic malignant syndrome. PMID- 2876096 TI - The innervation of the pyloric region of the crab, Cancer borealis: homologous muscles in decapod species are differently innervated. AB - The muscles of the pyloric region of the stomach of the crab, Cancer borealis, are innervated by motorneurons found in the stomatogastric ganglion (STG). Electrophysiological recording and stimulating techniques were used to study the detailed pattern of innervation of the pyloric region muscles. Although there are two Pyloric Dilator (PD) motorneurons in lobsters, previous work reported four PD motorneurons in the crab STG (Dando et al. 1974; Hermann 1979a, b). We now find that only two of the crab PD neurons innervate muscles homologous to those innervated by the PD neurons in the lobster, Panulirus interruptus. The remaining two PD neurons innervate muscles that are innervated by pyloric (PY) neurons in P. interruptus. The innervation patterns of the Lateral Pyloric (LP), Ventricular Dilator (VD), Inferior Cardiac (IC), and PY neurons were also determined and compared with those previously reported in lobsters. Responses of the muscles of the pyloric region to the neurotransmitters, acetylcholine (ACh) and glutamate, were determined by application of exogenous cholinergic agonists and glutamate. The effect of the cholinergic antagonist, curare, on the amplitude of the excitatory junctional potentials (EJPs) evoked by stimulation of the pyloric motor nerves was measured. These experiments suggest that the differences in innervation pattern of the pyloric muscles seen in crab and lobsters are also associated with a change in the neurotransmitter active on these muscles. Possible implications of these findings for phylogenetic relations of decapod crustaceans and for the evolution of neural circuits are discussed. PMID- 2876098 TI - Tricyclic epines. Novel (E)- and (Z)-11H-dibenz[b,e]azepines as potential central nervous system agents. Variation of the basic side chain. AB - The synthesis and pharmacological activity of new (E),(Z)-[6-(alkylamino)-11H dibenz[b,e]azepin-11- ylidene]acetonitriles 12-45 and (E),(Z)-[6-(aminoalkoxy) 11H-dibenz[b,e]azepin-11-ylidene] acetonitriles 46-51 are described. The introduction of the cyanomethylene group into the 11-position of the 11H dibenz[b,e]azepine framework has been carried out by a Wittig-Horner reaction under mild conditions. The (E),(Z) isomers were separated by fractional crystallization, assignment being achieved by X-ray analysis. A number of (E),(Z) [6-(alkylamino)-11H-dibenz-[b,e]azepin-11-ylidene] acetonitriles (12, 14, 16, 20) show potent neuroleptic activity (2-7 times that of clozapine) in animal tests. The screening included tests for sedative and anticholinergic activity in mice, apomorphine and tryptamine antagonism in rats, and muscle-relaxing activity in rabbits. The divergence in the activity profile in the case of the separated (E),(Z) isomers has been observed as an interesting new aspect: the (Z) isomers show a significantly higher sedative and muscle-relaxant activity, whereas the (E) isomers possess a higher anticholinergic efficacy and somewhat greater apomorphine antagonism. Broad changes in the basic side chain were made in order to investigate structure-activity relationships. The important geometrical parameters for the molecules, obtained by X-ray analysis, were compared with the corresponding features in dopamine agonists and antagonists. PMID- 2876099 TI - Synthesis and biological activities of dynorphin A analogues with opioid antagonist properties. AB - Dynorphin A, which displays a wide variety of physiological effects, binds to opioid receptors preferentially at the kappa receptor type. kappa-selective antagonists would be very useful as pharmacological and biochemical probes to study and better understand the action of dynorphin A at its preferred receptor. However, the development of such molecules has been elusive, and very few are known at this time. Taking these features into account, we have synthesized by the solid-phase procedure several analogues of dynorphin A containing various D amino acid substitutions. The binding properties of the peptides have been examined at three main opioid binding sites (mu, delta, and kappa) and their kappa selectivity determined. Their biological activities have been tested in three specific pharmacological assays for agonist and/or antagonist properties. Introduction of D-Trp substitution leads to analogues, in particular [D- Trp2,8,D Pro10]-, [D-Trp5,8,D-Pro10]-, and [D-Trp2,4,8,D-Pro10]dynorphin(1-11), showing antagonist properties in the isolated rabbit vas deferens preparation, a kappa specific bioassay. The antagonism against dynorphin A is weak, as indicated by the observed Ke values (433, 199, and 293 nM, respectively), and not very selective (kappa vs. mu). Such peptide analogues derived from the endogenous ligand and endowed with antagonist properties are the first ones reported to date and could open a promising way in designing more potent and selective kappa opioid antagonists. PMID- 2876100 TI - Preparation and analgesic activity of (-)-11 alpha-substituted 1,2,3,4,5,6 hexahydro-6 alpha,7-(methyleneoxy)-2,6-methano-3-benzazocines. AB - Dihydrocodeinone oxime (1) under Beckmann rearrangement conditions gave a product (2) that facilitated the preparation of (-)-11 alpha-substituted 1,2,3,4,5,6 hexahydro-6 alpha,7-(methyleneoxy)-2,6-methano-3-benzazocines, a hitherto little examined series of morphine partial structures. Compounds 7a and 12 gave good levels of agonist antinociceptive activity. Masking of the 8-oxygen function, as in 6 and 8, dramatically reduced mouse hot-plate activity, as did its loss (9). PMID- 2876102 TI - Neuroleptics from the 4a,9b-cis- and 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H pyrido[4,3-b]indole series. 2. AB - Compounds derived from 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4, 3 b]indole are consistently efficacious in displacing [3H]spiroperidol from striatal dopamine receptors in vitro. Derivatives bearing substituents at position 2, particularly those derived from butyrophenone moieties, are exceptionally potent in vivo. Compounds from the corresponding 4a,9b-cis series are substantially less potent in both in vivo and in vitro assays of neuroleptic activity. Although the cis and trans derivatives have, in some conformations, similar basic nitrogen atom to aromatic ring separations of about 5.1 A, the distance at which the basic nitrogen atom lies above or below the plane of the aromatic ring differs substantially between the two series. Consideration of these results in terms of this and earlier work indicates that the out-of-plane distance for the basic nitrogen in neuroleptic molecules may range from about 0 to about 0.90 A but may be optimized at about 0.55 A. PMID- 2876101 TI - Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists. AB - The resolution of three 2-substituted derivatives of idazoxan is described. The enantiomers show large separations in activity in a variety of in vitro and in vivo tests, and the active isomers are all potent and selective antagonists at the alpha 2-adrenoreceptor. The significance of these results in relation to those published on the enantiomers of idazoxan and to those on optically active alpha 2-adrenoreceptor agonists is discussed. PMID- 2876103 TI - Dopamine receptor modulation by Pro-Leu-Gly-NH2 analogues possessing cyclic amino acid residues at the C-terminal position. AB - The synthesis of several analogues of L-prolyl-L-leucylglycinamide (PLG) was carried out in which the glycinamide residue was replaced with the following cyclic amino acid residues: L- and D-prolinamide, (+)- and (-)-thiazolidine-2 carboxamide, L- and D-3,4-dehydroprolinamide, L-azetidine-2-carboxamide, L piperidine-2-carboxamide, and L-thiazolidine-4-carboxamide to give PLG analogues 2-10, respectively. The ability of these analogues to enhance the binding of the dopamine agonist ADTN (2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene) to dopamine receptors was determined by using bovine brain tissue. All of the PLG analogues synthesized in this study enhanced the binding of ADTN to central dopamine receptors. The percent enhancement of ADTN binding produced by analogues 2,3, and 7-10 at various concentrations was comparable to the percent enhancement produced by PLG. The PLG analogues Pro-Leu-(+)-thiazolidine-2-carboxamide (4), Pro-Leu-(-)-thiazolidine-2-carboxamide (5), and Pro-Leu-L-3,4-dehydroprolinamide (6), however, produced significantly greater enhancement (2-3-fold) in ADTN binding than did PLG. PMID- 2876104 TI - Synthesis of Pro-Leu-Gly-NH2 analogues modified at the prolyl residue and evaluation of their effects on the receptor binding activity of the central dopamine receptor agonist, ADTN. AB - Several analogues of L-prolyl-L-leucylglycinamide (PLG) were synthesized wherein the prolyl residue was replaced with other heterocyclic amino acid residues. Among the analogues synthesized were D-Pro-Leu-Gly-NH2 (2), less than Glu-Leu-Gly NH2 (3), Thz-Leu-Gly-NH2 (4), Pip-Leu-Gly-NH2 (5), Aze-Leu-Gly-NH2 (6), L-delta 3,4-Pro-Leu-Gly-NH2 (7), and D-delta 3,4-Pro-Leu-Gly-NH2 (8). These analogues were tested for their ability to enhance the binding of the agonist 2-amino-6,7 dihydroxy-1,2,3,4-tetrahydronaphthalene to central dopamine receptors. Analogues 2, 3, and 5-7 showed activity comparable to that of PLG, while the tripeptides 4 and 8 were found to be inactive. The results show that the N-terminal prolyl residue of PLG is not an essential requirement for this tripeptide's ability to modulate dopamine receptors. PMID- 2876105 TI - Neuroleptics from the 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole series. 3. Carboxamidoalkyl derivatives. AB - Substitution of position 2 of the 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H pyrido[4,3-b]indole nucleus with omega-carboxamidoalkyl substituents leads to compounds with exceedingly potent neuroleptic activity in in vitro and in vivo models. Although duration of activity is not as long as that of the analogous 4 hydroxy-4-(4-fluorophenyl)butyl derivatives reported previously, the absolute potency in vivo is greater. The ability of these compounds to bind with great affinity to dopamine (DA) receptors further defines the nature of the DA receptor auxiliary binding site as a hydrogen-bond donating site in addition to or instead of a lipophilic site as has been previously proposed. PMID- 2876106 TI - 3,7-Diazabicyclane: a new narcotic analgesic. AB - The synthesis of a series of 9-phenyl-3,7-diazabicyclanes and 9-(m-hydroxyphenyl) 3,7-diazabicyclanes is described. Members of both series were tested for antinociception in rat tail withdrawal and mouse acetic acid writhing assays. Their affinities for opiate receptors in rat brain homogenate were also determined. The 9-phenyl compounds, 1a-c, were inactive. However, the 9-(m hydroxyphenyl) analogues, 2a-c, were found to possess significant activity in the writhing assay, comparable to that of morphine. All activity was reversed by naloxone. PMID- 2876107 TI - Chromaffin cell heterogeneity of process formation and neuropeptide content under control and nerve growth factor-altered conditions in cultures of chick embryonic adrenal gland. AB - Adrenal glands from embryonic day 11 (E-11) chicks were cryostat-sectioned, and it was determined that tyrosine hydroxylase-like immunoreactive (TLI) cells, somatostatin-like immunoreactive (SLI) cells, and methionine-enkephalin-like immunoreactive (ELI) cells occupied chromaffin regions of the gland. Similar age adrenals were dissociated, and the cells were cultured under serum-free conditions. Cultured TLI cells, ELI cells, and SLI cells were characterized according to cell size, cell number, and neurite formation. ELI and SLI cells composed two largely separate populations, with SLI cells tending to have larger cell areas, to be more numerous, and to be less likely to form neurites than ELI cells. The population of TLI cells, although unique in itself, was diverse and numerous enough to include all or portions of the neuropeptide-immunoreactive populations. Neurites of some cells from each of the above populations were strongly immunoreactive for alpha neurofilament protein, and for NAPA73 neurofilament-associated protein. However, neurites could also be observed in all populations that showed poor immunoreactivity for these cytoskeletal proteins. Exogenously added NGF significantly increased neurite-like process formation among TLI and ELI cells, but not among SLI cells. Reductions in the number of neurite-like processes following treatment with anti-nerve growth factor (NGF) were not significant for any of the populations. However, if shorter and broader process were included, anti-NGF caused a significant reduction in total cell processes among TLI and ELI cells. Anti-NGF inhibition of process formation among ELI cells could be reversed with exogenous NGF. Neither NGF or anti-NGF treatments showed a significant effect on cell numbers among TLI and ELI populations. The implications are that a compound of antigenic and physiological similarity to mouse salivary NGF is made by embryonic chick adrenal cells in culture, but the effects of NGF do not appear to be the same for all neural-crest derived cells from the adrenal, and greater heterogeneity of phenotypes may exist among chromaffin cells than has previously been accepted. Some questions are also raised concerning the neurite-like nature of processes formed by some chromaffin cells in vitro. PMID- 2876108 TI - Beta-adrenergic stimulation of protein (arginine) methyltransferase activity in cultured cerebral cells from embryonic mice. AB - Several adrenergic effectors and neurotransmitters were tested as potential regulators of myelin basic protein (MBP) and histone methyltransferase activities. Both enzymes were specifically activated by beta-adrenergic agonists in a stereospecific manner. Cyclic AMP (but not AMP) stimulated the enzymes to the same extent as did the beta-adrenergic agonist, (-) isoproterenol. The studies suggest that beta-adrenergic agonists stimulate adenylate cyclase thereby causing an increased production of cyclic AMP which stimulates the methyltransferases. Cycloheximide addition to the reaction mixture did not affect the stimulation due to cyclic AMP, indicating that new protein synthesis is not involved in the cyclic AMP stimulation of the methyltransferases. Thyroid hormone (T3) has been shown to stimulate MBP methyltransferase [Amur et al, 1984] and could exert its stimulatory effect through beta-adrenergic-dependent systems. But the beta-adrenergic antagonist, propranolol, did not block the stimulation by T3, suggesting that the effect of T3 is not mediated through beta-adrenergic dependent systems. Thus, the methylation of MBP seems to be regulated both by T3 and by neurotransmitters and/or hormones mediating their effects through cyclic AMP production, whereas the methylation of histones seems to be regulated only by the latter. PMID- 2876110 TI - Hypernephroma associated with multiple endocrine neoplasia type I: a case report. AB - We report a case of multiple endocrine neoplasia type I and hypernephroma. Parathyroid hyperplasia, adrenocortical hyperplasia, a nodular goiter, multiple lipomas, a chromophobe adenoma of the pituitary and hypernephroma had all been diagnosed previously. All but the last are features consistent with the diagnosis of multiple endocrine neoplasia type I (Wermer's syndrome). The association of multiple endocrine neoplasia type I and hypernephroma may represent a new manifestation of this pleiotropic syndrome. PMID- 2876109 TI - Chloride-dependent binding sites for L-[3H]glutamate on dendrodendritic synaptosomal membranes of rat olfactory bulb. AB - Dendrodendritic synapses occur between granule cell dendrites and secondary dendrites of mitral cells within the olfactory bulb and are attainable in a subcellular fraction (DDS). Since the mitral cells are thought to utilize an excitatory amino acid as a neurotransmitter, we determined the pharmacologic specificity of Na+-independent L-[3H]glutamate binding to fresh membranes of DDS in 50 mM Tris-HCl, pH 7.1. Binding of L-glutamate to membranes of DDS was specific, Cl(-)-dependent, and saturable. Scatchard plots were analyzed by nonlinear regression analyses using the computer program LIGAND, and the data was best-fitted to a one-site model with KD of 0.56 +/- 0.04 microM and an apparent Bmax of 48 +/- 5 pmol/mg protein. Hill plots also indicated the presence of one site and no cooperativity (nH = 0.99 +/- 0.03). However, the relative effectiveness of several compounds in inhibiting L-glutamate binding to membranes of DDS clearly demonstrated the presence of more than one site. Electrophysiological studies suggest that 2-amino-4-phosphonobutyrate (APB) is a potent antagonist of evoked responses elicited by stimulation of mitral cell axons and that quisqualate is a potent agonist; both of these compounds were highly effective inhibitors of L-glutamate binding to DDS membranes. APB displaced about 70% of the sites labeled with 200 nM L-glutamate with a KI of 1.6 microM, whereas quisqualate inhibition of L-glutamate binding yielded a line that was curvilinear in the Scatchard plot and was resolved into two sites of relatively high affinity (KI values of 0.02 and 0.65 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876111 TI - HTLV-I and -II. New risks for recipients of blood transfusions? PMID- 2876112 TI - A survey of mosquitoes in Karachi area, Pakistan. PMID- 2876113 TI - Regulation of coronary blood flow by counteraction of coronary vascular alpha and beta adrenergic activation during experimental pliable coronary stenosis. AB - In order to evaluate the role of adrenergic receptor-mediated vasomotions of large epicardial coronary arteries in changing coronary blood flow (CBF), the effects of intracoronary norepinephrine (NE), 1.0 microgram/min, were examined in dogs with coronary stenosis which preserved stenosis vasomobility. In untreated dogs, NE caused no significant changes in CBF and stenosis resistance (SR). In dogs treated with propranolol, NE decreased CBF by 65 +/- 7.0% (mean +/- SE) and produced 12-fold intensification of SR followed by LV dP/dt reduction. Similar detrimental responses to NE were observed in dogs treated with atenolol. In dogs treated with phentolamine, NE increased CBF by 33 +/- 5.6% and decreased SR by 65 +/- 7.1%. When NE was administrated directly distal to the stenosis to exclude responses of the stenosed coronary segment, NE failed to affect CBF and SR. These results indicated that alpha receptor stimulation intensified stenosis severity, profoundly decreased CBF and evoked myocardial ischemia, whereas beta stimulation dilated coronary stenosis and increased CBF. The net effects of NE were due to balanced alpha and beta stimulation. Thus, disproportionate activation of alpha and beta (probably beta 1) adrenergic receptors in large coronary arteries with pliable stenosis could modulate their tone and plays an important role in the regulation of CBF. PMID- 2876114 TI - Enhanced renal sympathetic nerve activity in response to salt loading in rats. AB - To analyze the conflicting data on the relationship between sodium intake and sympathetic activity, the effects of a chronically excessive intake of sodium on renal sympathetic activity and blood pressure were investigated in normotensive rats. Renal sympathetic activity was estimated by urinary excretion of free norepinephrine (NE) and the turnover of NE in the kidneys. Blood pressure increased in rats receiving a high sodium diet when compared with that of the basal sodium diet. Urinary-free NE, epinephrine (E) and dopamine (DA) excretions in rats receiving a high sodium diet were enhanced significantly from those in the basal sodium diet. The turnover of NE in the kidneys was more enhanced in the high sodium group than in the basal sodium group. By blocking the sympathetic tone with ganglionic blockade, hexamethonium, enhanced excretion of urinary NE and elevation of blood pressure in response to salt loading were blocked to the levels of the basal sodium diet. These results suggest that a chronically excessive intake of sodium enhances the renal sympathetic and adreno-medullary activities, leading to a rise in blood pressure in normotensive rats. PMID- 2876115 TI - Comparison of vascular responses of isolated, perfused simian and canine coronary arteries to adrenergic agonists. AB - The vascular responses of the isolated, perfused simian left circumflex coronary arteries to adrenergic agonists were compared to those of canine coronary arteries in isolated, perfused preparations. Norepinephrine and epinephrine produced only vasoconstriction in monkey arteries in contrast to vasoconstrictor, vasodilator and biphasic responses of canine coronary arteries. Isoproterenol induced a dose-dependent vasodilatation. Salbutamol, a selective beta 2-agonist, produced either a slight vasodilatation or no response. Phenylephrine, a selective alpha 1-agonist, usually caused a marked vasoconstriction in a dose related manner in both preparations. Xylazine and clonidine, selective alpha 2 agonists, caused a slight vasoconstriction in low doses, but these two agonists relaxed both preparations in high doses. These observations suggest that adrenoceptor subtypes may be mainly alpha-1 and beta-1 in the large coronary arteries of monkeys and dogs and that the alpha-adrenoceptor is predominant in simian large coronary arteries. PMID- 2876116 TI - [Progress in anti-angina agents and drug therapy]. PMID- 2876117 TI - [Wermer's syndrome (multiple endocrine neoplasia, type I)]. PMID- 2876118 TI - Effects of pindolol, befunolol and melanin treated with adrenergic beta-blocking agents on lysosomal enzymes in bovine ciliary body and iris in vitro. AB - We studied biochemically the effects of pindolol, befunolol and melanin treated with beta-blockers on lysosomal enzymes in the ammonium sulfate fraction of the bovine ciliary body and iris in vitro. Acid phosphatase, beta-D-glucuronidase and alpha-D-mannosidase were not inhibited by the beta-blockers. N-acetyl-beta-D glucosaminidase and alpha-L-fucosidase activities were inhibited by pindolol and befunolol at high concentrations. After centrifugation of the enzyme fraction incubated with melanin, the enzyme activity in the supernatant decreased, possibly as a result of the affinity of lysosomal enzymes to melanin. When melanin was first treated with pindolol or befunolol, some lysosomal enzyme activities increased in the supernatant after removing the melanin, depending on the concentration of the beta-blocking agent. This increased activity may result from the loss of affinity of lysosomal enzymes to melanin caused by the beta blocking agent. PMID- 2876119 TI - Probable pre- and postsynaptic modifications by 5-hydroxytryptamine of contractile responses to electrical stimulation of isolated guinea-pig vas deferens. AB - Two kinds of electrical stimulation, low frequency stimulation (5 Hz, 1 msec, 5 pulses, every 20 sec) and high frequency stimulation (30 Hz, 0.05-0.1 msec, 10 pulses, every 20 sec), produced contractions in the isolated guinea-pig vas deferens. These responses were blocked by tetrodotoxin but not hexamethonium. Phentolamine potentiated the contractions produced by low frequency stimulation, while it reduced the contractions produced by high frequency stimulation. Diametrically, 5-hydroxytryptamine reduced the contractions produced by low frequency stimulation, while it potentiated the contractions produced by high frequency stimulation. These inhibitory and potentiating actions of 5 hydroxytryptamine were reversed by cyproheptadine and 2-bromolysergic acid diethylamide. Moreover, that 5-hydroxytryptamine produced a depolarization of the smooth muscle membrane was shown by the sucrose gap technique. The results suggest that a 5-hydroxytryptamine receptor exists pre- and postsynaptically in the neuroeffector transmission of the guinea-pig vas deferens, that the stimulation of the presynaptic receptor by 5-hydroxytryptamine inhibits the release of a transmitter from noradrenergic nerves, and that the stimulation of the postsynaptic receptor by a high concentration of 5-hydroxytryptamine produces a depolarization of the smooth muscle membrane, and this relates to the potentiation of contractile responses. PMID- 2876120 TI - Analysis of new imidazoline derivative-induced increase in the maximum response to norepinephrine in the rat vas deferens. AB - The effects of newly synthesized 5-imidazoline derivatives on the dose-response relationship to norepinephrine were investigated in the normal and denervated vasa deferentia of the rat. Three derivatives (K-3827, K-4011 and K-4300) exerted alpha-antagonistic action, the potency of which was similar to that of tolazoline. The pA2 values of these derivatives and currently known alpha antagonists (tolazoline, phentolamine and prazosin, but not yohimbine) in the denervated tissue were slightly but significantly larger than those in the normal tissue. All imidazoline derivatives and alpha-antagonists produced an increase in the maximum response to norepinephrine in the normal vas deferens. In the denervated tissue, however, K-3827, K-4011 and alpha-antagonists caused only a rightward shift of the dose-response curve to norepinephrine, but not an increase in the maximum response, i.e., relatively pure alpha-antagonism. In contrast, the other 3 imidazoline derivatives, K-4299 and K-6342 which exhibited neither alpha agonistic nor antagonistic action and K-4300, increased the maximum response to norepinephrine even after denervation. Their effects were nonspecific in that they also potentiated acetylcholine-induced contractions in both normal and denervated tissues. These 3 imidazoline derivatives antagonized the action of diltiazem. The effects of imidazoline derivatives and alpha-antagonists were discussed in relation to those of denervation, and the drug enhancement by 3 imidazoline derivatives was analyzed from the viewpoint of calcium movement. PMID- 2876121 TI - Peroxisome proliferator-induced hepatocarcinogenesis: histochemical analysis of ciprofibrate-induced preneoplastic and neoplastic lesions for gamma-glutamyl transpeptidase activity. AB - Previous studies revealed that putative preneoplastic and neoplastic lesions induced in the liver by Wy-14,643, a peroxisome proliferator, were gamma-glutamyl transpeptidase (GGT) negative. For ascertainment as to whether phenotypes of foci and carcinomas induced by all peroxisome proliferators are similarly GGT negative, altered areas (AAs), neoplastic nodules (NNs), and hepatocellular carcinomas (HCCs) induced in the livers of male F344 rats by chronic dietary administration of ciprofibrate (0.025% wt/wt in chow; CAS: 52214-84-3) were analyzed histochemically for GGT activity. Eighty-nine percent of AAs, 91% of NNs, and 91% of HCCs were GGT negative. The GGT-negative property of these various hepatic preneoplastic and neoplastic lesions persisted at 8 weeks after the withdrawal of ciprofibrate treatment. The results of this study indicate that the absence of GGT activity is a common feature in hepatic lesions induced by structurally unrelated peroxisome proliferators and is not related to the drug toxicity. The proposal was made that peroxisome proliferators do not derepress the activity of the GGT gene during hepatocarcinogenesis in the rat. PMID- 2876122 TI - [Effect of long-term anti-arrhythmia treatment on the status of ischemic heart disease patients]. AB - Standard ECG recording, prolonged ECG monitoring and bicycle ergometry were used in 329 coronary patients. Ventricular extrasystole of grades 2-5 (Lown's classification) was diagnosed in 126. The patients were randomly allocated to the main and control groups. Prolonged continuous treatment of the main-group patients with propranolol and other anti-arrhythmic drugs resulted in reduced occurrence of arrhythmic episodes, and lower heart rates and arterial blood pressure as well as alleviation of clinical anginal symptoms, as compared to the controls treated in local outpatient clinics. PMID- 2876123 TI - [Beta-adrenoblockaders and lipid metabolism]. PMID- 2876124 TI - [Effect of antianginal, hypotensive and diuretic agents on blood lipid composition]. PMID- 2876125 TI - [Improved results in the surgical treatment of cryptorchism]. PMID- 2876126 TI - [Correction of the hemodynamic disorders following abdominal surgical interventions in children]. PMID- 2876127 TI - [Therapeutic consequences of glaucoma treatment with different beta blockers in patients with obstructive respiratory tract diseases]. AB - In patients in whom chronic obstructive bronchial disease and chronic glaucoma had been diagnosed, the most important ventilation parameters and intraocular pressures were investigated in a double-blind cross-over study. The airway resistance, the forced expiratory volume within the first second, the thoracic volume, and the mean expiratory flow in these patients exhibited significant differences after treatment with non-cardioselective beta-blocking agents, depending on the beta-receptor stimulating action of this ophthalmic solution (Pindolol 1% eye drops) or without any intrinsic sympathicomimetic action (Metipranolol 0.6% eye drops). There was no fundamental difference in the intraocular pressure-lowering effect of these two locally applied beta-blocking solutions. This study implies that when selecting a beta-blocking ophthalmic solution for anti-glaucoma treatment, the existence of an ISA effect of these eye drops is relevant only to avoid systemic side effects such as bronchopulmonary obstruction. PMID- 2876128 TI - [Antiglaucomatous effectiveness of beta receptor blockers with special reference to metipranolol]. AB - Long-term treatment of glaucoma and ocular hypertension is being carried out increasingly by topical application of beta-adrenergic drugs. They bind to the beta 2-subtypes of beta-receptors in the unpigmented epithelia of the ciliary processes with high affinity. Aqueous humor production is thus inhibited. On the other hand the velocity of penetration through the cornea and the drug accumulation at this location increase with rising lipophilicity of the beta blocker used. In this respect timolol and metipranolol, which was recently introduced on the Austrian market, possess favorable pharmacokinetic characteristics due to their intermediate lipophilicity. A calculation shows that one drop of 0.1% metipranolol solution produces supramaximal concentrations for several hours at the place of pharmacodynamic action. This is confirmed by the clinical efficacy, at the same time reducing the risk of local and systemic side effects. PMID- 2876129 TI - [H2 receptor blocker or prostaglandin E in ulcer therapy?]. PMID- 2876130 TI - Hyperparathyroid glands contain G-17 and G-34 gastrin. AB - To determine if gastrin in hyperparathyroid glands is true gastrin or artifact and to determine the frequency of gastrin in parathyroid glands, 20 parathyroid glands from 11 patients with hyperparathyroidism but without MEA were extracted and analyzed for gastrin. The parathyroid glands from 4 out of 11 patients had measurable gastrin immunoreactivity (10.7 + 6 pg/mg tissue). Column separation chromatography confirmed that this was true gastrin (40% G-34; 50% G-17). Immunohistochemistry with ABC (avidin biotin complex) immunoperoxidase confirmed the presence of gastrin in cytoplasmic vesicles in scattered parathyroid cells. True gastrin does exist in some cells in some patients with hyperparathyroidism. PMID- 2876131 TI - Testicular seminomas in Saudi Arabia: clinical characteristics, prognostic indicators, and recommendations for management. AB - Thirty Saudi patients with pure testicular seminoma were treated at King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, between January 1977 and June 1983. Disease characteristics in Saudi Arabia including clinical findings, response to therapy, and prognosis are described and compared to those in other populations reported in the literature. Symptom durations were 3 to 42 months. Many of the patients presented with an extensive tumor burden and a poor performance status. There was a higher incidence of anaplastic seminoma and of cryptorchidism than in other series and a relatively high incidence of elevated betahuman chorionic gonadotropin (B-HCG). Patients initially underwent funiculo orchiectomy. Twenty-two patients received radiation therapy and four received chemotherapy. Patients with limited disease responded well to orchiectomy and radiation therapy. However, those with extensive tumor burden had an unsatisfactory response to radiation therapy. Preradiation chemotherapy is recommended for patients with massive retroperitoneal metastases, nodal disease above the diaphragm, or extranodal disease and patients with minimal or moderate sized retroperitoneal nodal disease associated with an elevated B-HCG. PMID- 2876132 TI - Nurse practitioner and physician assistant satellite health centers. The pending demise of an organizational form? AB - A national cohort of 44 rural satellite health centers originally staffed by nurse practitioners (NPs) and physician assistants (PAs) was studied in 1975 and resurveyed in 1979 and in 1984 to examine the viability of this type of health care delivery organization during a period of significant growth in the nation's physician supply. Twelve of these practices had ceased to function, although eight have been replaced by physician practices. Of the remaining 32, 14 have physicians on their staffs and 18 remain staffed only by NPs and PAs. Those centers staffed by physicians experience greater patient utilization, charge more for office visits, have larger budgets, and generate more of their budgets from fees for services and therefore appear to be more organizationally stable than centers staffed only by NPs and PAs. Although broader studies are needed for substantiation, these findings suggest that the period when NP/PA-staffed satellite health centers were important organizations for delivering care to previously underserved rural communities may be ending. PMID- 2876133 TI - Measurement of the effect of cardiovascular drugs by impedance cardiography in healthy subjects. AB - Impedance cardiography is a non-invasive electrical method designed to measure cardiac function on a beat-to-beat basis. Impedance changes within a constant high frequency AC-current field are detected by two thoracic electrodes. The potential changes within these two inner electrodes reflect impedance changes due to underlying pulsatile volume displacements. The relevance of the method was shown in investigations with a beta 1,beta 2-mimetic drug, a beta-blocker, an alpha-agonist, an alpha-blocker and a diuretic drug. PMID- 2876134 TI - Diagnosis of renal allograft rejection by analysis of fine-needle aspiration biopsy specimens with immunostains and simple cytology. AB - Fine-needle aspiration biopsy specimens of renal transplants were analysed by means of commercially available monoclonal antibodies and an immunoperoxidase stain. Three cellular features associated with acute cellular rejection were identified--heavy infiltrates of activated T cells or large mononuclear cells strongly expressing HLA-DR antigens, and HLA-DR expression by renal tubular cells. A combination of semiquantitative scores for these features correctly identified rejection in 32 of 34 cases, with no false positives in cases of cyclosporin nephrotoxicity or stable graft function. PMID- 2876135 TI - Oral contraceptive use and breast cancer in young women. A joint national case control study in Sweden and Norway. AB - The possible association between oral contraceptive (OC) use and the risk of breast cancer developing before the age of 45 was investigated by means of a population based case-control study in Sweden and Norway. Information was obtained by personal interview from 422 (89.2%) of all eligible patients with a newly diagnosed breast cancer from May, 1984, to May, 1985, and from 722 (80.6%) of all contacted age-matched controls. A multivariate analysis, which accounted for several possible confounding factors, revealed a significant (p = 0.03) association between total duration of OC use and breast cancer risk. The relative risk (RR) of breast cancer after 12 or more years of OC use was 2.2 (1.2-4.0). OC use for more than 7 years before first full-term pregnancy entailed an increased breast cancer risk (RR = 2.0 [1.0-4.2]) which was of borderline significance. When total duration of use was considered, the risk of breast cancer was virtually unrelated to age at first OC use and latency from first use. The results suggest that long-term use of OCs may increase the risk of breast cancer in young women. PMID- 2876136 TI - Risk factors for human immunodeficiency virus seropositivity among children 1-24 months old in Kinshasa, Zaire. AB - A prevalence study of antibody to human immunodeficiency virus (HIV) was conducted in Kinshasa, Zaire, among 258 children 2-24 months old who were in hospital, 191 children 1-20 months old who were attending a well-child clinic, and their mothers. 8% of the mothers of both groups of children were seropositive. Among children under 9 months old, 12 of 102 (12%) hospital inpatients and 11 of 136 (8%) clinic attenders were seropositive, while in the 9 24-month age group 20 of 156 (13%) hospital children and only 1 of 55 (2%) clinic children were seropositive (Fisher's exact test, p = 0.01). 61% of the seropositive children had seropositive mothers, indicating a high rate of vertical transmission. Factors associated with seropositivity among hospital children with seronegative mothers included male sex, increased lifetime number of medical injections, and previous blood transfusion or hospital admission. Among children who had not previously been transfused or admitted to hospital the seropositives had received more medical injections than the seronegatives (median 34.5 versus 14.5; Wilcoxon rank sum test, p = 0.006). HIV infection accounted for or complicated a substantial proportion of hospital paediatric admissions. Public health measures are urgently required to prevent parenteral and vertical transmission of HIV to infants and young children in Kinshasa. PMID- 2876137 TI - Association between anorectal dysplasia, human papillomavirus, and human immunodeficiency virus infection in homosexual men. AB - Cells from the anorectal mucosa of 61 homosexual men were examined microscopically for evidence of papillomavirus infection and dysplastic changes. There was cytological evidence of dysplasia with concomitant features of human papillomavirus (HPV) infection on at least one occasion in 24 men and of papillomavirus infection without dysplasia on at least one occasion in a further 26: dysplasia was present for over one year in 9 of 14 men who were re-examined. Dysplasia was associated with a history of anal warts, frequent receptive anal intercourse, presence of serum antibody to human immunodeficiency virus (HIV), and immune dysfunction as judged by a low CD4/CD8 ratio, but not with the lifetime number of sexual partners. The association of longlasting dysplasia with anti-HIV was independent of the association with immune dysfunction. Thus infection of anorectal mucosal cells with papillomavirus seems to be frequent among homosexual men and may predispose to dysplasia. PMID- 2876138 TI - Oral contraceptives and breast cancer. PMID- 2876139 TI - Molecular biology and chronic granulocytic leukaemia. PMID- 2876141 TI - Central vein catheterisation. PMID- 2876140 TI - What's new pussycat? Cowpox. PMID- 2876142 TI - Aminoglycoside toxicity. PMID- 2876143 TI - Measles vaccine once or MMR twice? PMID- 2876144 TI - Does mild atypia on a cervical smear warrant further investigation? AB - 228 women referred to a colposcopy clinic over a 10-year period with mildly atypical cervical cytology had a histological diagnosis established by colposcopically directed biopsy. Of the 187 women (82.0%) who had dyskaryosis on the referral smear, 129 (69%) had cervical intraepithelial neoplasia (CIN) grade II or III on histology, as did 12 (29.2%) of the 41 women without dyskaryosis. 27.6% of smears taken at the time of colposcopy had normal cytology, although a third of these women had CIN II or III diagnosed on histology at that time. The poor correlation between mildly atypical cervical cytology and histology suggests that the practice of relying on cytology alone for the surveillance of women who have already had an atypical smear should be discouraged. PMID- 2876145 TI - Hydatidiform mole in England and Wales 1973-83. AB - The number of cases of hydatidiform mole (HM) registered annually in England and Wales has risen since 1973 to 1.54 per 1000 live births in 1983. For women over 50 the risk per pregnancy was 411 times and for girls under 15 it was six times greater than that for women aged 25-29. 7.75% of patients had chemotherapy for invasive mole or choriocarcinoma. Patients who had had oxytocin-induced or prostaglandin-induced uterine evacuation or hysterotomy were more likely to need chemotherapy. Human chorionic gonadotropin (HCG) was undetectable by 56 days after evacuation in 42% of patients, none of whom required chemotherapy; a considerable reduction in follow-up time for this subgroup is proposed. For patients whose HCG values became normal more than 56 days after evacuation and stayed normal for 6 months the risk of recrudescent disease was 1 in 286. In subsequent pregnancies the risk of a second HM was 1 in 76 and that of a third was 1 in 6.5. 11 (0.2%) patients died, 2 from drug-resistant choriocarcinoma. PMID- 2876146 TI - Triage of casualties after nuclear attack. AB - Casualties from a nuclear attack on the United Kingdom would overwhelm the health services, and health workers would be faced with many more people seeking help than could be offered treatment. Discussion is needed to determine which methods of medical and non-medical triage would be acceptable and feasible. PMID- 2876147 TI - Real-time cardiac imaging of adults at video frame rates by magnetic resonance imaging. PMID- 2876148 TI - Effects of prostacyclin and orally active stable mimetic agent RS-93427-007 on basic mechanisms of atherogenesis. PMID- 2876149 TI - Human papilloma virus DNA in oesophageal carcinoma. PMID- 2876151 TI - Spirochaetes, Lyme disease, and multiple sclerosis. PMID- 2876150 TI - DR2-negative narcolepsy. PMID- 2876152 TI - Aminoacid losses on haemofiltration. PMID- 2876153 TI - Rioprostil and duodenal ulcer. PMID- 2876154 TI - Pancreatic stone protein in serum of patients with pancreatitis. PMID- 2876155 TI - Non-secretion of ABO blood group antigens predisposing to infection by Haemophilus influenzae. PMID- 2876156 TI - Maternal smoking during pregnancy and the risk of childhood cancer. PMID- 2876157 TI - Rheumatoid arthritis and tuberculosis. PMID- 2876158 TI - Aspirin and cataract. PMID- 2876159 TI - Floppy disc psychiatry. PMID- 2876160 TI - From Nazi holocaust to nuclear holocaust. PMID- 2876161 TI - Soviet physicians denied exit visas. PMID- 2876162 TI - Measles and the immunosuppressed child. PMID- 2876164 TI - Catheter fractures in implantable vascular access systems. PMID- 2876163 TI - Voluntary euthanasia. PMID- 2876165 TI - Oral contraceptives and breast cancer. PMID- 2876166 TI - Cyclosporin and idiopathic nephrotic syndrome. PMID- 2876167 TI - Is chronic renal transplant rejection a non-immunological phenomenon? PMID- 2876168 TI - Poliomyelitis in Finland. PMID- 2876169 TI - Failure of high intrauterine insemination of husband's semen. PMID- 2876170 TI - Horizontal transmission of HIV infection between two siblings. PMID- 2876171 TI - Viral origin of hairy leukoplakia. PMID- 2876172 TI - High-altitude hypoxia and the brain. PMID- 2876173 TI - Occipital headache in rheumatoid cervical facet joint arthritis. PMID- 2876174 TI - Glucose stick misuse. PMID- 2876175 TI - Perinatal data using geographically defined populations. PMID- 2876177 TI - Hepatitis B vaccine for medical staff. PMID- 2876178 TI - Spastic paraparesis: a possible sexually transmitted viral myeloneuropathy. PMID- 2876176 TI - Reversible coma due to intrathecal baclofen. PMID- 2876180 TI - Jet lag and melatonin. PMID- 2876179 TI - HTLV-I and tropical spastic paraparesis in Africa. PMID- 2876181 TI - Pyridoxine in primary hyperoxaluria type I. PMID- 2876182 TI - Thyroglobulin autoantibodies and acetylcholinesterase. PMID- 2876183 TI - Effect of calcium supplementation on diastolic blood pressure in young people with mild hypertension. AB - In a double-blind trial 90 mildly hypertensive subjects aged 16-29 years were randomly assigned to 1 g calcium per day or placebo. Calcium supplementation did not affect systolic blood pressure, but at six and twelve weeks diastolic blood pressure had fallen by 3.1 (p = 0.04) and 2.4 (p = 0.11) mm Hg, respectively, more in the calcium group than it had in the placebo group. Subjects with a baseline plasma parathyroid hormone (PTH) higher than the median showed a 6.1 mm Hg (p = 0.01) greater fall in diastolic blood pressure after six weeks and 5.4 mm Hg (p = 0.01) after twelve than in the placebo group. The fall in diastolic blood pressure was greater in the calcium group than in the placebo group in subjects with a lower than median serum total calcium and in those with a large bodyweight. Calcium supplementation may lower blood pressure in young people with mildly raised blood pressure, particularly in those with high plasma PTH and/or low serum total calcium. PMID- 2876184 TI - Natural history of human immunodeficiency virus infection in Zaire. AB - The natural history of human immunodeficiency virus (HIV) infection in Zaire was determined by identifying in October, 1984, 125 seropositive hospital personnel without signs or symptoms and 145 age and sex matched seronegative controls from the same population. Between July, 1985, and February, 1986, 67 seropositives, including 38 men and 29 women, and 113 seronegatives were interviewed and examined by an observer who did not know their serological status. The acquired immunodeficiency syndrome (AIDS) had developed in 1 seropositive and no seronegatives (rate difference, 1.3/100 person-years [py]; 95% confidence interval 0-3.3/100 py); AIDS-related complex or generalised lymphadenopathy had developed in 8 seropositives (12%) and 1 seronegative (1%) (rate ratio, 13.2; 95% confidence interval 1.3-134.6); and minimal lymphadenopathy had developed in 19 seropositives (28%) and 8 seronegatives (7%) (rate ratio, 3.9; 95% confidence interval 1.8-8.4). These data provide the first estimates for rates of progression to AIDS or AIDS-related conditions among healthy HIV seropositive heterosexual adults. Rates observed in this study are similar to those reported in US or European homosexual or bisexual men. PMID- 2876185 TI - In-vitro test of haptocorrin degradation for biological diagnosis of exocrine pancreatic dysfunction using duodenal juice collected during endoscopy. AB - An in-vitro test of degradation of haptocorrin, a cobalamin-binding glycoprotein, was used to diagnose exocrine pancreatic dysfunction. This radioisotopic test (TDH) required only 50 microliters duodenal juice collected during endoscopy after stimulation with 1 U/kg secretin intravenously. The initial reaction mixture, composed of salivary haptocorrin saturated with cobalt-57-labelled cyanocobalamin and unsaturated intrinsic factor, was incubated with 25 microliters duodenal juice. The percentage of degraded haptocorrin was estimated from the proportion of labelled cyanocobalamin that was transferred from haptocorrin to intrinsic factor. The TDH result was 41.6 +/- 31.7% (SD) in a group of chronic pancreatitis patients (n = 22) and 91.5 +/- 4.8% in the control group (n = 47). The sensitivity and specificity for exocrine pancreatic dysfunction were estimated as 0.91 and 0.96, respectively, for a lower limit of normal values of 81.7%. A hyperbolic relation was found between the TDH and the trypsin or chymotrypsin activity in duodenal juice (p less than 0.001). In this study, the N-benzoyl-tyrosyl-p-aminobenzoic acid test was less sensitive than the TDH, since its result was abnormal in only 64% of the patients. The TDH was easier to carry out and less time-consuming than the determination of pancreatic enzyme output in duodenal juice collected after hormonal stimulation. PMID- 2876186 TI - Induction of involuntary movements by peripheral trauma: an analogy with causalgia. AB - Ten patients are described in whom various involuntary movement disorders developed after trauma that was predominantly or entirely peripheral. The interval between injury and onset of movement disorder ranged from 48 hours to 3 years; the injured and painful part was the area initially affected by involuntary movements, although more widespread involvement subsequently occurred. These clinical features resemble the phenomena experienced by some patients with causalgia and suggest the possibility of common mechanisms. PMID- 2876187 TI - Development of circulating antigen assay for rapid detection of acute schistosomiasis. AB - A circulating antigen assay to detect acute schistosomiasis mansoni in experimentally infected mice has been developed. The competitive-inhibition enzyme-linked immunosorbent assay uses rabbit serum prepared against purified cercarial antigen. The assay detects a 100-worm infection as early as 1 week after exposure; circulating antigen levels in mouse serum exceeded 0.1 microgram/ml. Preliminary characterisation of the cercarial antigen shows that it is a hydrophobic polypeptide of approximate molecular weight 41,000. A rapid and accurate diagnosis of acute schistosomiasis in travellers would facilitate appropriate chemotherapy before the onset of pathology. A circulating antigen assay would also be valuable for seroepidemiological studies in areas where the disease is endemic. PMID- 2876188 TI - Localisation of heparin in mast cells. AB - Heparin is localised in mast cells as an activator of the contact system. The potent anticoagulant properties of heparin confine this activation to the top half of the intrinsic pathway, and coagulation is prevented. Certain mast cells contain chondroitin sulphate E, which can also activate the contact system but is a weak inhibitor of coagulation. The localisation of these mast cells to the intestine suggests that coagulation is required for effective inflammatory response in the intestinal wall. PMID- 2876189 TI - Bacterial arthritis. PMID- 2876190 TI - Oral cholera vaccines. PMID- 2876191 TI - Blunt trauma to the heart. PMID- 2876192 TI - Colchicine in amyloidosis. PMID- 2876193 TI - Screening strategies for cervical cancer. PMID- 2876194 TI - Parathyroid gland localisation. PMID- 2876195 TI - Stress fractures. PMID- 2876196 TI - Overuse syndrome in musicians: prevention and management. PMID- 2876197 TI - Differential diagnosis of motoneurone disease from other neurological conditions. AB - Analysis of 422 patients with clinical diagnoses of motoneurone disease (MND), multiple sclerosis, cervical spondylosis with myelopathy, or stroke, from two referral centres, suggested a simple four-step algorithm for diagnosing MND. The algorithm provided a 98% sensitivity (true positive diagnosis) and 86% specificity, and therefore gives a baseline for diagnostic criteria suitable for use in clinical research of MND. PMID- 2876198 TI - Benign metastases from thyroid malignancies. AB - Two patients harbouring cervical lymph node metastases from papillary carcinoma of the thyroid have remained free of symptoms after treatment with suppressive doses of thyroid hormone for 25 and 34 years, respectively. There is evidence that these local metastases are relatively innocuous and may even exert a protective effect in the course of this low-grade malignancy. It is suggested that currently accepted modes of treatment may be unnecessarily invasive and should be reassessed. PMID- 2876199 TI - Increased expression of lymphocyte functional antigen in Down syndrome. PMID- 2876200 TI - Probucol versus eptastatin in hypercholesterolaemic diabetics. PMID- 2876201 TI - Restriction enzyme MaeIII for prenatal diagnosis of alpha 1-antitrypsin deficiency. PMID- 2876202 TI - Adenocarcinoma of prostate in 40-year-old body-builder. PMID- 2876203 TI - Anti-phospholipid antibody and pregnancy wastage. PMID- 2876204 TI - Passive smoking, birthweight, and oestrogens. PMID- 2876205 TI - High cyclosporin levels after bone marrow transplantation associated with hypertriglyceridaemia. PMID- 2876206 TI - Chloramphenicol resistance in Haemophilus influenzae. PMID- 2876207 TI - Amoxycillin prophylaxis and infective endocarditis. PMID- 2876208 TI - Home parenteral nutrition for children. PMID- 2876209 TI - Comparison of a microplate anti-HBs EIA kit with AUSAB EIA. PMID- 2876210 TI - Magnetic resonance imaging for cervical whiplash injuries. PMID- 2876211 TI - Pancreatic cancer in mother and daughter. PMID- 2876212 TI - A national food policy. PMID- 2876213 TI - Home, hospital, or birthroom. PMID- 2876214 TI - Improved use of medical resources. PMID- 2876215 TI - Differential diagnosis of Cushing's syndrome. PMID- 2876216 TI - Gastric stump cancers. PMID- 2876218 TI - Hospital outbreaks of Clostridium difficile. PMID- 2876217 TI - Prevention of postoperative deep-vein thrombosis. PMID- 2876219 TI - Disseminated histoplasmosis and AIDS in Switzerland. PMID- 2876220 TI - Blood donations reactive for HIV in Western blot, but non-infective in culture and recipients of blood. PMID- 2876221 TI - Ascertaining viral safety of human blood derivatives. PMID- 2876223 TI - Myalgia, leucopenia, and the sickling trait. PMID- 2876222 TI - HTLV-I and HIV infection in drug addicts in Italy. PMID- 2876224 TI - Prognosis and treatment in myelodysplasia. PMID- 2876225 TI - Topical surfactant therapy for recurrent herpes simplex. PMID- 2876226 TI - Tropical diabetes. PMID- 2876227 TI - Thyroid cancer after 131I treatment. PMID- 2876228 TI - Thyroid radiation dose in Britain arising from the Chernobyl accident. PMID- 2876229 TI - Amniotic bands and malformations in child born after pregnancy screened by chorionic villus biopsy. PMID- 2876230 TI - Cytochrome P-450 immunolocalization in human liver. PMID- 2876231 TI - First-trimester fetal diagnosis for haemoglobinopathies: report on 200 cases. AB - First-trimester prenatal diagnosis by DNA analysis was found to be possible in 224 (80%) of 281 families at risk of having a child with beta-thalassaemia major. 200 prenatal diagnoses, mainly for beta-thalassaemia or sickle-cell anaemia, were made by means of chorionic villus sampling and fetal DNA analysis. The overall fetal loss rate was 6.7%, the majority being in the first half of the programme. There was one misdiagnosis. Prenatal diagnosis was also carried out successfully for both pairs of twins in two pregnancies. Comparison of these results with 53 prenatal diagnoses made with DNA prepared from amniotic fluid suggests that the first-trimester procedure is more reliable. If further experience confirms that chorionic villus sampling has an acceptably low risk for both mother and fetus it will largely replace other methods for prenatal diagnosis of the haemoglobin disorders and other single-gene conditions. PMID- 2876232 TI - Prenatal diagnosis of alpha 1-antitrypsin deficiency by restriction fragment length polymorphisms, and comparison with oligonucleotide probe analysis. AB - Prenatal diagnosis of sixteen pregnancies at risk for alpha 1-antitrypsin (AAT) deficiency has been achieved by restriction fragment length polymorphism (RFLP) analysis and compared with diagnostic results using hybridisation of M and Z specific oligonucleotides. The results of both tests were in accord for all samples, although under routine laboratory conditions RFLP analysis was more reliable. Because RFLP analysis does not depend on the type of mutation it was possible, in the product of an MZ and SZ mating, to predict an MZ rather than an MS phenotype using the RFLP method. The strong linkage dysequilibrium between an AvaII RFLP and the Z allele increases its diagnostic usefulness. Even so it seems reasonable to use oligonucleotide analysis in families where no siblings are available for comparison. In all other situations RFLP analysis is as accurate and reliable as oligonucleotide analysis and is technically easier, making it the preferred means of diagnosis for informative kindreds. PMID- 2876233 TI - Symptomatic assessment of patients with heart failure: double-blind comparison of increasing doses of diuretics and captopril in moderate heart failure. AB - Ten patients with moderate heart failure who still had symptoms despite 40 mg frusemide daily were treated with increased doses of frusemide and the addition of captopril in randomised order. Four different methods were used to assess the patients' response to treatment. Both treatments improved symptom-limited exercise tolerance, higher-dose frusemide having a more favourable effect. Perceived exertion during submaximal exercise was reduced by similar amounts by both treatments. The time taken to walk 100 m at a self-selected slow speed was reduced by both treatments; again higher-dose frusemide had a more beneficial effect. The higher dose of frusemide also had a more favourable effect on visual analogue scores for dyspnoea, fatigue, and general well-being. PMID- 2876234 TI - Enzyme replacement in nervous tissue after allogeneic bone-marrow transplantation for fucosidosis in dogs. AB - Bone-marrow transplantation after total lymphoid irradiation in an alpha-L fucosidase-deficient dog raised the enzyme activity in both visceral and neural tissues with consequent reduction in the severity of storage lesions. These results offer hope that early marrow transplantation may prevent the development of disease in neurovisceral storage disorders. PMID- 2876235 TI - Effective and lasting growth-hormone suppression in active acromegaly with oral administration of somatostatin analogue SMS 201-995. AB - Oral administration of the long-acting somatostatin analogue, SMS 201-995 (Sandoz), was assessed in five patients with active acromegaly, four of whom had not responded to pituitary irradiation. Doses of 4-8 mg three times daily lowered mean 24 h growth-hormone concentrations by over 50% in every case, with suppression to below 10 mU/l for several hours after the morning dose. Despite effective suppression of serum insulin levels, deterioration in glucose tolerance was very slight, and the drug had no side-effects. Orally administered SMS 201 995 avoids the need for multiple daily injections and is potentially valuable in the medical treatment of acromegaly. PMID- 2876236 TI - Reversed-role chemotherapy for resistant cancer. AB - Chemotherapeutic agents that have come into clinical use because of their selective effect against cancers have limited success mainly because many cancer cells become resistant to them. Some chemotherapeutic agents inhibit DNA synthesis in normal cells but not in tumour cells so that nucleoside analogues with cell-killing potential can be incorporated into cancer cells when they continue to synthesise DNA in the presence of agents that stop DNA synthesis in normal cells. The potential of halogenated pyrimidines as sensitisers of cancers to ionising and photo-irradiation might be extended by giving them with agents that inhibit their uptake by normal tissues. A similar approach might also be used with conventional cytotoxic chemotherapy. Radiolabelled pyrimidine analogues may have a role in treating tumours resistant to inhibitors of DNA synthesis. They may also prove useful agents for gamma-camera imaging when normal tissue uptake is blocked. PMID- 2876237 TI - Use of autoanalyser to examine urinary-red-cell morphology in the diagnosis of glomerular haematuria. PMID- 2876238 TI - Early diagnosis and screening for pancreatic cancer. PMID- 2876239 TI - Bronchial asthma and the environment. PMID- 2876240 TI - Bone-marrow transplantation for neurovisceral storage disorders. PMID- 2876241 TI - Plagiocephaly and torticollis in young infants. PMID- 2876242 TI - Clostridium difficile--a neglected pathogen in chronic-care wards? PMID- 2876243 TI - Trimethoprim resistance. PMID- 2876244 TI - Randomised trial of community-based centre versus conventional hospital management in treatment of alcoholism. AB - 151 problem drinkers (105 men and 46 women) were recruited from the general medical and psychiatric services of a district general hospital and were allocated randomly to a community-based day centre (ACCEPT) or standard hospital inpatient and outpatient services. 115 patients (79%) were followed up at 12 months. The group as a whole showed improvement in all outcome indices at the 3 month follow-up, and this was maintained at 6 and 12 months. Patients assigned to ACCEPT services claimed to have reduced their alcohol intake (55%) more than their hospital counterparts (37%), and this was confirmed by their informants. Patients referred from the psychiatric services reduced their alcohol intake more than those from general medical services. It is concluded that treatment at a community day centre is at least as cost effective as hospital treatment of alcohol abuse. PMID- 2876245 TI - Why do research on research? AB - The importance of research evaluation is now well recognised in some quarters but this activity is being looked upon as essentially negative by others. We believe this view to be mistaken. The case for investing some money in research evaluation is essentially a very straightforward one. It is clear that a significant fraction of the money spent on research will be wasted (ie, will produce no usable data--positive or negative--on any time-scale and will be of no educational or training value). The problem is, and has always been, that there is no way of knowing in advance which fraction of the resources will be wasted. That is the nature of research and we would not argue that it could or should be otherwise. Research is about exploration and discovery and it is inevitable that some scientific endeavours will be fruitless. Research evaluation can help to minimise resource wastage and thus the case for conducting research on research is entirely positive. Analytical techniques are available to examine the ways in which we train research workers, fund research workers, and assess research outputs; and these should be applied with a view to improving the system. There is also a strong case for setting up an effective mechanism for strategic forecasting and planning, and an urgent need to take a radical look at the entire range of biomedical research activities in the UK. It is essential that the research community should take steps to evaluate its performance and adopt a positive approach to planning. If it does not do so, assessments will be made by those without a fundamental understanding of the nature of the enterprise, and the prospects for any further increases in public support would appear to be bleak. PMID- 2876246 TI - HLA-DR2 correlates with rapid-eye-movement sleep latency in normal human subjects. PMID- 2876247 TI - Placebo-controlled trial of topical cyclosporin in severe alopecia areata. PMID- 2876248 TI - Predicting gentamicin resistance from annual usage in hospital. PMID- 2876249 TI - Consensus analysis. PMID- 2876251 TI - Awareness of onchocerciasis. PMID- 2876252 TI - Meningococcal disease in south-west of England. PMID- 2876250 TI - Treatment of acute lymphoblastic leukaemia: a terminological plea. PMID- 2876253 TI - Meningococcal infections and eradication of the carrier state. PMID- 2876254 TI - Meningococcal serotypes and serogroup B disease in north-west Europe. PMID- 2876255 TI - Panic attacks and aspartame. PMID- 2876256 TI - Polymyositis, molecular mimicry, and autoimmunity. PMID- 2876257 TI - Safety of piroxicam. PMID- 2876258 TI - Cultured skin for burn injury. PMID- 2876259 TI - Reduced fibrinolytic activity as cardiovascular disease risk factor. PMID- 2876260 TI - Identification of elderly hypertensives. PMID- 2876262 TI - Somatostatin and heat sensitivity in multiple sclerosis. PMID- 2876261 TI - Clonidine and smoking. PMID- 2876263 TI - What to do about drug abuse. PMID- 2876264 TI - Tobacco and asbestos litigation. PMID- 2876265 TI - Incentives to take up health services. PMID- 2876266 TI - Paroxysmal hemiglossal twisting. PMID- 2876267 TI - Delayed recovery of sleep and melatonin rhythms after nightshift work in Antarctic winter. PMID- 2876268 TI - Needlestick HIV seroconversion in a nurse. PMID- 2876269 TI - Red cell charge in glomerular disease. PMID- 2876270 TI - AIDS and African swine fever virus. PMID- 2876271 TI - Mental handicap with psychiatric illness. PMID- 2876272 TI - Rheumatoid arthritis and tuberculosis. PMID- 2876273 TI - Smallpox in an Italian mummy. PMID- 2876274 TI - Risk of transmission of human papillomavirus by vaginal specula. PMID- 2876275 TI - Inadvertent abuse of amphetamines in street heroin. PMID- 2876276 TI - Health for all: some critics less critical. PMID- 2876277 TI - Cytotoxic protein molecules generated as a consequence of ethanol metabolism in vitro and in vivo. AB - A non-dialysable cytotoxic activity developed in the supernatants of human blood monocyte-derived macrophages cultured in the presence of ethanol and in the serum of three healthy volunteers who drank 500-700 ml wine over 20-35 min. On 'Sephacryl S-300' gel filtration of the culture supernatants and the serum samples from the subjects who took alcohol, the cytotoxic activity eluted together with albumin molecules. Studies of human serum and of various commercially purchased human serum protein fractions treated with carbon-14 labelled acetaldehyde and non-radioactive acetaldehyde, respectively, provided strong circumstantial evidence that the cytotoxic proteins were albumin molecules that had become complexed with acetaldehyde generated by the metabolism of ethanol. The cytotoxic activity developing in vivo was greatest 6-10 h after the consumption of ethanol started, when blood alcohol levels were normal or only slightly high. The appearance of a circulating long-acting cytotoxic macromolecule after the ingestion of ethanol may be of considerable importance in clarifying the mechanisms underlying ethanol-induced tissue damage. PMID- 2876278 TI - Controlled study of respiratory responses during prolonged measurement in patients with chronic hyperventilation. AB - The respiratory responses of 17 patients with chronic hyperventilation but without demonstrable organic disease (group H) to various manoeuvres were compared with those of 21 healthy controls (group C). The responses were tested according to a 60 min protocol in which periods of rest were replaced by exercise, voluntary hyperventilation (VHV), reading, and CO2 inhalation. 5 patients with severe resting hypocapnia were investigated overnight during sleep. Chronic hyperventilation was of two types--persistent or provoked by exercise or VHV. It was due to modest increases in tidal volume and respiratory frequency but was generally not conspicuous. End-tidal PCO2 levels were gradually corrected to near normal during sleep but not by inhalation of CO2. PMID- 2876279 TI - Platelet-derived growth factors as possible mediators of vascular proliferation in the sporadic haemolytic uraemic syndrome. AB - Mitogenic activity was measured in matched plasma and serum samples from 17 children with typical epidemic haemolytic uraemic syndrome (HUS), 13 with atypical sporadic HUS, 7 with other renal diseases, and 8 normal children. The serum mitogenic activity of the normal children (median 18.35, range 15-35 U/ml) greatly exceeded that of plasma (median 5.4, range 1.04-11.9 U/ml). Patients with atypical sporadic HUS had raised plasma mitogenic activity (median 9.35, range 0 35 U/ml, p less than 0.01). Both plasma and serum from children with the typical epidemic form of HUS had low or undetectable mitogenic activity (median for plasma 1.0, range 0-5.9 U/ml, p less than 0.001; median for serum 1.85, range 0 23.8 U/ml, p less than 0.005). These low concentrations in typical epidemic HUS were associated with the presence of an inhibitor of cell growth. The results suggest that there is intravascular release of platelet mitogens in atypical sporadic HUS and that these mitogens may therefore be mediators of the vascular proliferative lesions. PMID- 2876280 TI - Colonoscopy findings in symptomatic patients without X-ray evidence of colonic neoplasms. AB - Colonoscopy was carried out in 97 patients with persistent large-bowel symptoms in whom double-contrast barium enemas were either normal or showed diverticular disease alone. In 37 the X-ray was normal, but colonoscopy showed 9 polyps and 3 carcinomas. In 60 patients with barium enemas showing diverticular disease alone colonoscopy revealed 13 polyps and 1 carcinoma. Of the 4 carcinomas 1 was Dukes' A, 2 Dukes' B, and 1 Dukes' C. 23 of the 26 patients with a neoplastic lesion at colonoscopy had rectal bleeding, compared with only 40 of the 71 without a lesion. The frequency of neoplasia in those with a normal barium enema was 32%, compared with 23% in those whose X-ray showed diverticular disease. Colonoscopy, rather than double-contrast barium enema, should be the first line of investigation in patients with persistent large-bowel symptoms, especially rectal bleeding. PMID- 2876281 TI - Retinal microembolism during cardiopulmonary bypass demonstrated by fluorescein angiography. AB - Fluorescein angiography was used to study retinal microvascular perfusion in 20 patients undergoing coronary artery surgery. Colour retinal photographs and fluorescein angiograms were obtained preoperatively and at 5-14 days postoperatively. In 10 patients retinal fluorescein angiograms were also obtained intraoperatively during cardiopulmonary bypass, and all were found to have retinal microvascular occlusions after 40-160 min of extracorporeal circulation. 3 patients had in addition focal leakage of fluorescein, and 6 had foci of abnormal drainage of dye. These changes are consistent with retinal microembolism, and appeared to have resolved by the time of the postoperative study. No new pathological features appeared in the retina after surgery. Intraoperative fluorescein angiography of the retina may prove valuable for investigation of cerebrovascular microembolism in the territory of the internal carotid artery during cardiopulmonary bypass in man. PMID- 2876283 TI - Chymopapain and the intervertebral disc. PMID- 2876282 TI - A human tumour model. AB - An approach to the management of patients with large (greater than 4 cm) operable breast cancers is described. The conventional sequence of mastectomy followed by systemic therapy is reversed, allowing accurate measurements of response to individual forms of endocrine therapy or chemotherapy. Such a method not only permits individual selection of appropriate systemic therapy, but also allows clinical response to be related to histological and biochemical tumour parameters. A response was observed in eleven of twenty-three patients to endocrine treatment and in twelve of thirteen to combination chemotherapy. In five of the latter the response was histologically complete. PMID- 2876284 TI - Hyperkalaemia in diabetic ketoacidosis. PMID- 2876286 TI - Chronic contained rupture of abdominal aneurysms. PMID- 2876287 TI - Surgical manpower. PMID- 2876285 TI - Management of borderline personality disorders. PMID- 2876288 TI - Biocompatible implants for reconstruction of the ear. PMID- 2876289 TI - Where to draw the line. PMID- 2876290 TI - Ecology of orthopoxviruses and use of recombinant vaccinia vaccines. AB - Little is known of the ways in which orthopoxviruses are maintained in nature, and the role of wild-life reservoirs requires further investigation. This lack of information is important in view of proposals to use as vaccines recombinant vaccinia viruses which carry genes for other immunising antigens. The possibility that such strains may become established in nature, as vaccinia may have in Indian buffaloes, and/or undergo genetic hybridisation with existing orthopoxviruses should be considered. PMID- 2876291 TI - Postvagotomy diarrhoea put into perspective. AB - Truncal vagotomy and drainage is still the commonest operation for duodenal ulcer in the United Kingdom, despite its known association with diarrhoea. The frequency and severity of diarrhoea were compared in 102 randomly selected men 10 or more years after truncal vagotomy and pyloroplasty (TVP) and a control group of 62 men taking long-term maintenance cimetidine treatment 2 or more years after healing of duodenal ulcer. 53% of the TVP group still had diarrhoea attacks compared with only 7% of the cimetidine group (p less than 0.001). Of the TVP patients, 11% had continuous diarrhoea and a further 22% at least one attack a week. 24% were displeased with the change in bowel function, and 8% complained that diarrhoea still seriously affected their lives. This side-effect is unacceptable and truncal vagotomy should now be avoided whenever possible. PMID- 2876293 TI - Strokes in mild hypertension: diastolic rules. PMID- 2876292 TI - Useless drugs are not placebos: lessons from flunarizine and cinnarizine. PMID- 2876294 TI - Lioness versus lobby. PMID- 2876295 TI - Flexion contractures: a forgotten symptom in Addison's disease and hypopituitarism. PMID- 2876296 TI - Closed-chest atrioventricular junction ablation by high-frequency energy transcatheter desiccation. PMID- 2876297 TI - Valproate-induced inhibition of urea synthesis and hyperammonaemia in healthy subjects. PMID- 2876298 TI - Tryptophan-trazodone treatment of aggressive behaviour. PMID- 2876299 TI - Antibody-targeted therapy of cancer. PMID- 2876300 TI - Antibody-guided radiation therapy via the CSF for malignant meningitis. PMID- 2876302 TI - Butane lighters, an unexpected hazard for babies. PMID- 2876301 TI - Adjuvant chemotherapy in early breast cancer. PMID- 2876303 TI - Bone marrow transplantation and radiation accidents. PMID- 2876304 TI - Bone-marrow transplantation in childhood lymphoblastic leukemia. PMID- 2876305 TI - Reciprocal interference of host-versus-graft and graft-versus-host-reactions. PMID- 2876306 TI - Diluted samples in HIV antibody assays. PMID- 2876307 TI - Lack of HIV transmission by casual contact. PMID- 2876308 TI - Rapid prenatal diagnosis of Down's syndrome with in-situ hybridisation of fluorescent DNA probes. PMID- 2876309 TI - Prevalence of female breast cancer observed in 517 unselected necropsies. PMID- 2876310 TI - Impedance cardiography in heart failure. PMID- 2876311 TI - Literacy, parity, family planning, and maternal mortality in the Third World. PMID- 2876313 TI - Salbutamol for pertussis. PMID- 2876312 TI - Chopsticks dysphagia. PMID- 2876314 TI - Measles, mumps, and rubella vaccine. PMID- 2876315 TI - Misclassification as a factor in passive smoking risk. PMID- 2876317 TI - Soft-tissue sarcoma and exposure to dioxins. PMID- 2876316 TI - Food and health policy. PMID- 2876318 TI - Eperythrozoonosis in man. PMID- 2876319 TI - 6-Mercaptopurine-related leucopenia and in vivo xanthine oxidase activity. PMID- 2876320 TI - Non-invasive measurement of ophthalmic artery pressure by ophthalmomanometry Doppler. PMID- 2876321 TI - Lipid peroxidation and Parkinson's disease. PMID- 2876322 TI - Differential diagnosis of Cushing's syndrome. PMID- 2876323 TI - Sex ratios in neural tube defects. PMID- 2876324 TI - Transplacental transmission of hepatitis B virus. PMID- 2876325 TI - Pneumococcal vaccine prevents death from acute lower-respiratory-tract infections in Papua New Guinean children. AB - In three double-blind placebo-controlled trials of pneumococcal capsular polysaccharide vaccines against death from acute lower-respiratory-tract infections (ALRI), children were vaccinated at 6 months to 5 years of age. The efficacy of the vaccines against ALRI as the sole cause of death was estimated at 59% in children vaccinated when younger than 5 years (p = 0.008) and 50% in children vaccinated when younger than 2 years (p = 0.043). Mortality from all causes was 19% less in the vaccinated group. PMID- 2876326 TI - Is homoeopathy a placebo response? Controlled trial of homoeopathic potency, with pollen in hayfever as model. AB - The hypothesis that homoeopathic potencies are placebos was tested in a randomised, double-blind, placebo-controlled trial. The study model chosen compared the effects of a homoeopathic preparation of mixed grass pollens with placebo in 144 patients with active hayfever. The homoeopathically treated patients showed a significant reduction in patient and doctor assessed symptom scores. The significance of this response was increased when results were corrected for pollen count and the response was associated with a halving of the need for antihistamines. An initial aggravation of symptoms was noted more often in patients receiving the potency and was followed by an improvement in that group. No evidence emerged to support the idea that placebo action fully explains the clinical responses to homoeopathic drugs. PMID- 2876328 TI - Absence of pre-S2 antibodies in natural hepatitis B virus infection. AB - Antibodies to the host "self" component human serum albumin (HSA) and to its receptor are induced by the pre-S2 encoded aminoacid sequence (120-145) of the middle surface protein on the hepatitis B virus (HBV) particle and are produced as part of the immune response during acute HBV-infection. The antibodies disappeared rapidly during the convalescence phase and were not detectable in patients with naturally acquired immunity to HB. These data raise questions about the importance of anti-pre-S2 antibodies for long-term protection against HBV infection. The coexistence of HBV-DNA with antibodies to native HSA (nHSA) in 13/16 patients with biopsy proven liver disease and of HBV-DNA with anti-pre-S2 in 10/13 patients argues against the attribution of virus eliminating properties to antibodies directed against pre-S2 determinants. In fact circulating anti-nHSA and anti-pre-S2 persisted in 16/17 and 13/17 patients, respectively, with major HBV-induced liver disease but not in symptomless HBsAg carriers. This finding suggests that continuous production of antibodies against the "self" component HSA and/or its receptor structures are associated with the pathogenesis of chronic HBV-induced liver disease. Pre-S2 coded peptide sequences should thus not be incorporated into HB vaccines. PMID- 2876327 TI - Acute pulmonary embolism treated with tissue plasminogen activator. AB - Recombinant human tissue-type plasminogen activator (rt-PA) was given via a peripheral vein to 36 patients with angiographically documented pulmonary embolism. The regimen was 50 mg/2 h followed by repeat angiography and, if necessary, an additional 40 mg/4 h. By 6 h, 34 of 36 patients had angiographic evidence of clot lysis, slight in 4, moderate in 6, and marked in 24. The quantitative score improved 21% by 2 h and 49% by 6 h. Fibrinogen decreased 30% from baseline at 2 h and 38% from baseline at 6 h. 2 patients had major complications: in one, bleeding from a pelvic tumour required surgery; in the other, who had had coronary artery bypass surgery eight days earlier, pericardial tamponade developed. These initial results in selected patients make a case for expanded investigational use of peripheral intravenous rt-PA in pulmonary embolism. PMID- 2876329 TI - Cerebral morphological abnormalities associated with non-alcoholic cirrhosis. AB - Disturbance of cerebral morphology, as assessed from computed tomography (CT) scan images, was related to liver function in patients with non-alcoholic cirrhosis. These findings show that even in well compensated cirrhosis there are measurable disturbances of cerebral morphology, the extent of which is related to severity of liver dysfunction. PMID- 2876330 TI - Predicting chronicity in depression. PMID- 2876331 TI - Lysosomal storage diseases. PMID- 2876332 TI - Analgesics, agranulocytosis, and aplastic anaemia: a major case-control study. PMID- 2876333 TI - Research on healthy volunteers. PMID- 2876334 TI - Driving after stroke. PMID- 2876335 TI - Parents in the anaesthetic room? PMID- 2876336 TI - Prediction of outcome after curative resection for large bowel cancer. AB - Prospectively collected information on 2524 patients who had undergone "curative" resection for colorectal cancer was analysed to establish the rank-order of importance of both clinical and pathological factors affecting outcome. The patients were divided into two groups. In the first, a statistical weighting was established for each prognostic factor and those that influenced long-term survival were, in order of importance, lymph node status, tumour mobility, number of lymph nodes positive for tumour, presence of bowel obstruction, and depth of primary tumour penetration. Factors that influenced in-hospital mortality were cardiopulmonary complications, intraabdominal sepsis (without anastomotic leak), presence of bowel obstruction, and age. In the second group these mathematical weightings were applied, and the predicted and observed outcomes were in close agreement. Statistical techniques of this kind will be of value in prognosis and in analysis of the results of new treatment regimens. PMID- 2876337 TI - Artificial food additive intolerance in patients with angio-oedema and urticaria. AB - 43 children who presented with angio-oedema and/or urticaria and who responded to an additive-free diet were challenged with artificial food additives in a double blind study. 24 children reacted to 1 or more of the additives. 18 children did not react to any additives and remained well when a normal diet was re introduced. Aspirin sensitivity was found in only 1 of the 24 children who could not tolerate additives. Atopy was less common in these patients than in the general population. The mechanism of additive intolerance is unknown and double blind challenge is the only reliable means of diagnosis. PMID- 2876338 TI - Evidence of inadequate humidification of inspired gas during artificial ventilation of newborn babies in the British Isles. AB - Data on routine humidifier settings used in respiratory support for newborn babies were obtained from 242 neonatal units in the British Isles. For each of the most commonly used humidifiers inspired gas humidity was measured under routine clinical conditions with an electronic hygrometer. Most endotracheally intubated babies breathe inspired gas of well below physiological humidity (44 mg H2O/l) and many below the minimum recommended for adults by the British Standards Institution (33 mg H2O/l). Inadequate humidification could contribute to several complications of artificial ventilation in newborn babies by inhibiting mucociliary clearance. PMID- 2876339 TI - Do we need informed consent? PMID- 2876340 TI - Excessive chemotherapy-related myelotoxicity in children with Down syndrome and acute lymphoblastic leukaemia. PMID- 2876341 TI - Brown-Sequard syndrome due to spinal cord infarction after subclavian vein catheterisation. PMID- 2876342 TI - Cyclosporin, HLA matching, and transfusions in kidney transplants. PMID- 2876343 TI - Over-use syndromes in musicians. PMID- 2876344 TI - Innocent pets and Paget's disease? PMID- 2876346 TI - Enalapril-induced cough. PMID- 2876345 TI - Myocardial ischaemia during intravenous ritodrine treatment: is it so rare? PMID- 2876347 TI - Persistence of vaginal vault granulation. PMID- 2876348 TI - Asthma deaths and inhaler type. PMID- 2876349 TI - Fatal poisoning and membrane stabilising activity. PMID- 2876351 TI - Declining incidence of gonorrhoea in London: a response to fear of AIDS? PMID- 2876350 TI - Transplacental transmission of hepatitis B virus. PMID- 2876352 TI - Declining incidence of syphilis among homosexual men in Stockholm. PMID- 2876353 TI - Pseudo-Kaposi sarcoma. PMID- 2876354 TI - False-positive Western blot reactions to human immunodeficiency virus in blood donors. PMID- 2876355 TI - Oral contraceptives and breast cancer. PMID- 2876356 TI - Meningococcal infection in Lanarkshire. PMID- 2876358 TI - Sodium and water depletion in ileostomy patients. PMID- 2876359 TI - A stromal role in epithelial metaplasias? PMID- 2876357 TI - Captopril versus hydrochlorothiazide/triamterene in mild-to-moderate hypertension in the elderly. PMID- 2876360 TI - Cervical screening. PMID- 2876361 TI - Gamma interferon and psoriasis. PMID- 2876362 TI - High prevalence of invasive Haemophilus influenzae disease in central Australia, 1986. PMID- 2876363 TI - Does angiotensin-II protect against strokes? PMID- 2876364 TI - Mental handicap with psychiatric illness. PMID- 2876365 TI - Trimethoprim resistance. PMID- 2876366 TI - Red blood cell surface charge in nephrotic syndrome. PMID- 2876367 TI - Temperature-dependent binding of hydrophilic beta-adrenergic receptor ligands to intact human lymphocytes. AB - Important differences in binding characteristics between agonists and antagonists of the beta-adrenergic receptor have been described. However, these observations have been complicated since most available antagonists are much more lipophilic than agonists. In order to separate out those binding characteristics of agonist vs. antagonist from those characteristics of lipophilic vs. hydrophilic ligands, we have studied competition of the hydrophilic ligands isoproterenol (agonist) and CGP-12177 (antagonist) with [125I]iodopindolol binding in intact human lymphocytes. Analyzing competition curves from assays performed at 13 degrees C, 25 degrees C and 37 degrees C we demonstrated that at lower temperatures there was a decrease in IC50 for isoproterenol but not for CGP-12177. Using cells preincubated with isoproterenol then extensively washed, competition curves with both isoproterenol and CGP-12177 were biphasic, and characterized by the appearance of a population of receptors with a low affinity for both hydrophilic ligands. Furthermore, at lower temperatures the biphasic nature of these curves was accentuated and was characterized by a 6-fold and 40-fold increase in the apparent KD of a population of low affinity sites for isoproterenol and CGP 12177, respectively. PMID- 2876368 TI - Effect of small intestinal resection on somatostatin binding to cytosol of rabbit gastric mucosa. AB - Small bowel resection in the rabbit increased gastric (fundus and antrum) somatostatin content and decreased the number of somatostatin binding sites (but not their corresponding affinity values) in gastric (fundus and antrum) cytosol three weeks after surgery. Five weeks after resection the number of somatostatin binding sites at both fundic and antral levels as well as antral somatostatin content returned towards control values whereas the fundic concentration of the peptide remained increased. Present results together with the known inhibitory role of somatostatin on various gastric functions suggest that the gastric alterations showed by animals subjected to small bowel resection may be due, at least in part, to the observed decrease of the number of gastric somatostatin binding sites. PMID- 2876369 TI - Putative neurotransmitters in three experimental filariasis models. AB - Some putative neurotransmitters in three experimental filariasis models were investigated by a new relevant chromatographic method, sensitive and specific. No catecholaminergic compounds have been detected, but serotonin was found in Dipetalonema vitae. However, further investigations revealed very high levels of gamma amino butyric acid (GABA) in the macro-filariae. These data allow us to foresee new fields in filariasis therapeutics. PMID- 2876371 TI - Psychological treatment of phobic anxiety associated with adjuvant chemotherapy. AB - A 50-year-old patient with breast cancer was about to withdraw from her adjuvant chemotherapy regimen because of a long-standing phobia about being injected, which had been compounded by anxieties that were associated with the severe side effects of adjuvant chemotherapy. She experienced a conditioned nausea response to hospital and medical situations. A psychological programme that incorporated relaxation training, systematic desensitization by way of the patient's visual imagination and videotape modelling, allowed her to complete the course of chemotherapy and to feel less anxious in hospital and medical settings. PMID- 2876370 TI - Effect of glibenclamide on pancreatic hormone release from isolated perifused islets of normal and cysteamine-treated rats. AB - The effect of glibenclamide, a sulfonylurea agent, on islet hormone secretion, particularly on glucagon was studied using isolated perifused pancreatic islets of normal and cysteamine-treated rats. In normal rat islets, glibenclamide enhanced both insulin and somatostatin release in normoglycemic (50 mg/dL) and glucopenic (0 mg/dL) states, as well as under the condition of arginine stimulation. In contrast, glibenclamide stimulated glucagon release only transiently, then suppressed it in a sustaining manner in each state. In the cysteamine-treated islets, as expected, somatostatin concentrations in the perifusate remained unchanged during the infusion of arginine and/or glibenclamide. Under this condition, glibenclamide enhanced insulin release to the same extent as seen in normal islets, and again markedly inhibited glucagon release. These observations indicate that in isolated perifused rat pancreatic islets, glibenclamide suppresses glucagon secretion independently of D cell stimulation. It is concluded that glibenclamide may exert its inhibitory effect directly on A cell rather than through paracrine action of concomitant somatostatin release, and that the suppression of glucagon secretion by glibenclamide may, in part, contribute to the antidiabetogenic effect of this compound. PMID- 2876372 TI - Benzodiazepine dependence. PMID- 2876373 TI - The role of drugs in the treatment of opioid addicts. PMID- 2876374 TI - A quantitative method of analyzing the interaction of slightly selective radioligands with multiple receptor subtypes. AB - Subclasses of receptors exist for most neurotransmitters. Frequently, two subtypes of receptors coexist in the same tissue and, in some cases, they mediate the same physiological response. In tissues with two classes of binding sites for a given hormone, an estimate of the proportion of each class of binding sites is obtained by inhibiting the binding of a single concentration of a radioligand with a selective unlabeled ligand. Accurate estimates of the density of each class of receptors will only be obtained, however, if the radioligand is entirely nonselective. Selectivity of just 2- to 3-fold can markedly influence the results of subtype analysis. The conclusion that a radioligand is nonselective is usually based on the results of a saturation binding curve. If Scatchard analysis of such data results in a linear plot, then it is concluded that the radioligand is nonselective. However, Scatchard analysis cannot distinguish between a radioligand that is nonselective and one that is slightly selective. The use of a slightly selective radioligand can lead to errors of 50% or more, depending on the concentration of the radioligand relative to the Kd values of the two classes of sites. A new analytical method has been developed that can be used to quantitate 2- to 3-fold differences in the affinity of two distinct classes of binding sites for a radioligand. This new approach requires that a series of inhibition experiments with a selective unlabeled ligand be performed in the presence of increasing concentrations of the radioligand. Analysis of the resulting inhibition curves, utilizing the mathematical modeling program MLAB on the PROPHET system, yields accurate estimates of the density of each class of receptor as well as the affinity of each receptor for the labeled and unlabeled ligands. This approach was used to determine whether 125I-iodopindolol shows selectivity for beta 1- or beta 2-adrenergic receptors. A series of inhibition curves was generated with the unlabeled ligands ICI 89,406 (beta 1-selective) and ICI 118,551 (beta 2-selective), using membranes prepared from C6 glioma cells. These cells contain both beta 1- and beta 2-adrenergic receptors. 125I Iodopindolol was determined to be 3-fold selective for beta 2-adrenergic receptors. Since the sensitivity of this approach is superior to that of Scatchard analysis, it is likely that other radioligands, previously thought to be nonselective, will be shown to be selective when analyzed by this method. PMID- 2876375 TI - Identification of messenger RNA for glutamate dehydrogenase using a spectrophotometric probe. AB - Specific messenger RNA for glutamate dehydrogenase was partially purified from a calf liver polysomal poly(A)-mRNA fraction by sucrose density gradient centrifugation. Enzyme activity in the translational incubation mixture was detected by measuring NADH oxidation in the presence of alpha-ketoglutarate and ammonia as a decrease in absorbency 340-442 nm in a dual wavelength Aminco DW-2 spectrophotometer. PMID- 2876376 TI - [Distortion of ceramometal fixed bridges by heat treatment]. PMID- 2876377 TI - The classification of vasculitis and a reappraisal of allergic granulomatosis and angiitis (Churg-Strauss syndrome). PMID- 2876378 TI - Therapeutic approach to the vasculitic syndromes. PMID- 2876380 TI - Stroke and alcohol consumption. AB - We conducted a retrospective case-control study to investigate a possible association between alcohol intake and stroke. Reported recent alcohol consumption and biochemical and hematologic markers of alcohol intake were examined for 230 patients with stroke (20 to 70 years old) and compared with concurrently collected data on controls matched for age, sex, and race. A single estimate of current intake was used as a measure of alcohol consumption. Among men, the relative risk of stroke (adjusted for hypertension, cigarette smoking, and medication) was lower in light drinkers (those consuming 10 to 90 g of alcohol weekly) than in nondrinkers (relative risk, 0.5), but was four times higher in heavy drinkers (consuming greater than or equal to 300 g weekly) than in nondrinkers. Because very few women in our study drank heavily, we were unable to determine whether heavy alcohol intake influenced the risk of stroke in women. With increasing serum concentrations of the biochemical markers of alcohol intake (aspartate aminotransferase, uric acid, and gamma-glutamyl transferase), we observed similar trends in the relative risk of stroke. Only the erythrocyte mean cell volume did not follow this pattern. We conclude that heavy alcohol consumption is an important and underrecognized independent risk factor for stroke in men, but our data are not adequate to settle the issue for women. Our conclusions are qualified by our reliance on reported recent alcohol consumption as the primary measure of intake. PMID- 2876379 TI - gamma-Glutamyl transpeptidase activity in Ascaris suum. AB - Using histochemical techniques gamma-glutamyl transpeptidase activity has been localized mainly in the cuticle-hypodermis in Ascaris suum. The specific activity of gamma-glutamyl transpeptidase was 3.87 +/- 0.49 mumol h-1 (g tissue)-1 in cuticle-hypodermis as compared to gastrointestinal tract, where it was 0.07 +/- 0.02 mumol h-1 (g tissue)-1, and muscle and reproductive tract where it was less than 0.001 mumol h-1 (g tissue)-1. When cuticle sections were incubated with labelled glutamine a large portion of the glutamine nitrogen was recovered as ammonia which indicated glutamine uptake and utilization by the cuticle hypodermis. Collectively these histochemical and biochemical data support the fact that gamma-glutamyl transpeptidase activity is found in the cuticle hypodermis of A. suum and this may be an indication that amino acid absorption could occur through the cuticle via the gamma-glutamyl cycle. PMID- 2876381 TI - Concomitant infection with HTLV-I and HTLV-III in a patient with T8 lymphoproliferative disease. PMID- 2876382 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43-1986. An 11-year-old girl with a rash, ataxia, and cranial nerve palsies. PMID- 2876383 TI - Improvement in headache associated with prolactinoma during treatment with a somatostatin analogue: an "N of 1" study. PMID- 2876384 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 44-1986. An 80-year-old woman with Paget's disease and severe hypercalcemia after a recent fracture. PMID- 2876385 TI - Opioid receptors for the dynorphin peptides. PMID- 2876386 TI - Reverse phase HPLC of peptides: application to the opioid peptides. PMID- 2876387 TI - Enzymes in the metabolism of opioid peptides: isolation, assay, and specificity. PMID- 2876388 TI - Virtuoso design of drugs. PMID- 2876389 TI - Novel subunit-subunit interactions in the structure of glutamine synthetase. AB - We present an atomic model for glutamine synthetase, an enzyme of central importance in bacterial nitrogen metabolism, from X-ray crystallography. The 12 identical subunits are arranged as the carbon atoms in two face-to-face benzene rings, with unusual subunit contacts. Our model, which places the active sites at the subunit interfaces, suggests a mechanism for the main functional role of glutamine synthetase: how the enzyme regulates the rate of synthesis of glutamine in response to covalent modification and feedback inhibition. PMID- 2876391 TI - Medical education. What now? PMID- 2876390 TI - Characterization of postsynaptic alpha 1-adrenoceptors in the rabbit iris dilator smooth muscle. AB - Interactions of several alpha-adrenoceptor agonists and antagonists with their receptors were studied in rabbit and guinea pig iris dilator smooth muscle and rabbit aortic strips using pharmacological procedures. In rabbit iris dilators and aortic strips, noradrenaline acted as a full agonist, while oxymetazoline, clonidine and tizanidine acted as partial agonists. The dissociation constants of full and partial agonists in the dilators, calculated after irreversible blockade of a proportion of the active receptors with phenoxybenzamine, were similar to those in the aortic strips. Furthermore, the relative intrinsic efficacies of partial agonists were practically equal in the two tissues, suggesting that these drugs act on the same alpha-adrenoceptors. Since the alpha 2-agonists clonidine and tizanidine had low affinity in the rabbit dilators, the alpha-adrenoceptors in this tissue appear to be of alpha 1-type. These results were further supported by the fact that the pA2-value of prazosin, an alpha 1-antagonist, was approximately 2 log units higher than that of yohimbine, an alpha 2-antagonist. However, pA2-values of four quinazolines (prazosin, bunazosin, SM911 and SM2470) and two yohimbine alkaloids (yohimbine and corynanthine) were significantly lower in the rabbit dilator muscle than in rabbit aortic strips. Two imidazoline antagonists (phentolamine and tolazoline) and a phenethanolamine (labetalol) acted on the alpha 1-adrenoceptors in the two tissues nonselectively. These results suggest that alpha 1-adrenoceptors in the rabbit dilator muscle and aortic strips may not be identical and that both selective and nonselective antagonists which act on these receptor sites exist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876393 TI - [The non-palpable testis; difficulties in diagnosis and treatment]. PMID- 2876392 TI - [Diagnosis of cryptorchism: data from a youth health service and surgical findings]. PMID- 2876394 TI - [Prevalence of undescended testis in the first 4 years of life; a longitudinal study]. PMID- 2876395 TI - [Dopamine receptors: fundamental and clinical aspects]. PMID- 2876396 TI - [Sleeping depression. Psychopathological and biochemical findings in a single case analysis]. PMID- 2876397 TI - Autoradiographic distribution of dynorphin1-9 binding sites in primate brain. AB - The autoradiographic distribution of kappa opioid binding sites was evaluated in sections of monkey brain using the selective ligand [3H]dynorphin1-9. Kappa receptors were highly concentrated in the deep layers of the cerebral cortex, the substantia nigra, the hippocampus and the dentate gyrus. Lower levels were seen in the outer cortical layers, the caudate nucleus, the claustrum, parts of the amygdala and the cerebellum. These data are discussed in relation to the distribution in brain of the endogenous kappa-ligand. PMID- 2876398 TI - Concentration-dependent suppression by beta-adrenergic antagonists of the shift in ocular dominance following monocular deprivation in kitten visual cortex. AB - We showed that beta-adrenergic receptor antagonists blocked the shift in ocular dominance following brief monocular deprivation in young kittens. Localized microperfusion of propranolol into the kitten visual cortex reduced the expected shift in the ocular dominance approximately 2 mm away from the center of perfusion. The blocking effect, however, did not reach an area approximately 5 mm from the perfusion center, suggesting that beta blockers work in a concentration dependent fashion in the present paradigm. We further studied the concentration effect relationship by widely changing the concentration of beta blockers (propranolol and sotalol) stored in an osmotic minipump. The proportion of binocular cells increased from 0.13 to 0.67 when the concentration of propranolol was increased from 10(-6)M to 10(-2)M, giving the half-maximum effect (binocularity, 0.40) at about 10(-4)M propranolol. However, the maximum binocularity obtained with the sotalol perfusion under the comparable condition was apparently much lower (0.45) than that with propranolol. Accordingly, the half-maximum binocularity (0.30) was obtained at about 10(-5)M sotalol. We also noted the presence of a linear, inverse relation between the logarithmic concentration of the beta blockers and the extent of the shift in ocular dominance as measured by the proportion of monocular cells which responded exclusively to stimulation of the nondeprived eye. The latter decreased from 0.75 to 0.25, when the former was increased from 10(-6)M to 10(-2)M (in an osmotic minipump). The two beta blockers behaved similarly in this correlation. The intracortical spread of locally perfused [3H]propranolol was studied at the end of the cortical perfusion which lasted for a week. The radioactivity was highest at the perfusion center and rapidly declined with increasing distance, leveling off approximately 3 mm from the perfusion center. The average "dilution factor" of locally perfused [3H]propranolol was calculated as about 1/170 of the original solution in an area of physiological recordings (approximately 2 mm from the perfusion center). Applying the "dilution factor" of 1/170, we estimated the approximate concentration of beta blockers needed at the recording sites to obtain the half-maximum effect; it was about 5.8 X 10(-8)M for sotalol. Taken together, the present results were interpreted as suggesting that there is a positive correlation between the number of activated beta-adrenergic receptors within the visual cortex and the extent of changes in ocular dominance following monocular deprivation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876399 TI - Variations in 3,4-dihydroxyphenylacetic acid concentration are correlated to single cell firing changes in the rat locus coeruleus. AB - The purpose of this study is to see whether variations in the catechol oxidation peak in the locus coeruleus would be closely related with variations in single cell firing, and would be independent of the mechanism triggering the variation of neuronal activity. Single unit and electrochemical (differential pulse voltammetry) recordings were performed, respectively on the left and right locus coeruleus of anaesthetized rats. The variations in single unit activity were induced using well known stimulatory mechanisms (yohimbine, hypovolemia, indirect activation using a 5-hydroxytryptamine central agonist RU 24969, RU 24722 known to activate noradrenergic metabolism), or inhibitory (clonidine, morphine) models. This was done in addition to successive activation or inhibition (reversal of oxotremorine with scopolamine, antagonism of clonidine by piperoxane). In all the experimental conditions, variations in the catechol oxidation current followed variations in single cell activity. Furthermore, the catechol oxidation current variations correlated significantly to changes in the firing rate. Such a close correlation between a catechol oxidation peak, and the electrical activity of the locus coeruleus cell bodies supports the use of catechol oxidation current variations as a good indirect index of functional activity in noradrenergic locus coeruleus perikarya. This suggests a close relationship between dopamine metabolism and electrical activity in locus coeruleus cell bodies. PMID- 2876400 TI - Localization of dynorphin gene product-immunoreactivity in neurons from spinal cord and dorsal root ganglia. AB - Using spinal cord and dorsal root ganglion cell cultures, we have studied the immuno-histochemical distribution of several peptide products of the dynorphin gene. With antibody directed toward the midregion of dynorphin A, peptide immunoreactivity was found exclusively in the cell bodies of spinal cord neurons. Antibody directed toward the amino- or carboxy-terminus of dynorphin A revealed peptide-immunoreactivity in the neurites, as well as perikarya. Spinal cord neurons also expressed dynorphin B- and alpha-neo-endorphin-immunoreactivities in both cell bodies and neurites. Dorsal root ganglion neurons cultured from embryonic tissue expressed dynorphin A-(1-13)-, dynorphin A-(9-17)- and dynorphin B-immunoreactivities in their perikarya. Sensory neurons obtained from dissociated adult ganglia similarly expressed dynorphin-immunoreactivity immediately upon inoculation into culture. Embryonic and adult murine sensory ganglia from the sacral region more frequently expressed dynorphin than did cells obtained from other spinal levels. Expression of dynorphin-immunoreactivity by sensory neurons was not influenced by elevated levels of Nerve Growth Factor or spinal cord conditioned medium. These data indicate that intrinsic spinal cord neurons may modulate sensory and spinal function in rather subtle ways via the expression of several different opioid peptide products of the dynorphin gene, in addition to the opioid peptides produced by the proenkephalin A gene. Beyond this, the observation of dynorphin-related peptides in dorsal root ganglion neurons suggests that these opioid peptides may have a specialized role in primary afferent neurotransmission. PMID- 2876402 TI - [Considerations on the use of long-acting neuroleptics in a mental health center]. AB - In this work the Authors while explaining the clinical results achieved by the use of long-acting neuroleptic drugs through the parenteral way, do make a few remarks on the psychological aspects connected with their administration as well as in their influence on the course of the cure. PMID- 2876401 TI - Use of high concentrations of glutaraldehyde for immunocytochemistry of transmitter-synthesizing enzymes in the central nervous system. AB - Aldehyde fixatives containing high concentrations of glutaraldehyde, usually used for conventional electron microscope studies, were successfully used for immunocytochemistry of transmitter synthesizing enzymes, glutamate decarboxylase and tyrosine hydroxylase, in the rat central nervous system. Although a high concentration of glutaraldehyde could cause tremendous non-specific staining, this was almost completely absent after treating sections with 1% sodium borohydride for 30 min. Furthermore, it was shown that a high concentration of glutaraldehyde might cause no appreciable reduction of the antigenicities of glutamate decarboxylase and tyrosine hydroxylase when compared with fixatives containing a low concentration of glutaraldehyde. It is suggested that fixatives containing high concentrations of glutaraldehyde are very useful, not only for conventional electron microscope studies, but also for light and electron microscope immunocytochemistry of some antigens, including glutamate decarboxylase and tyrosine hydroxylase. PMID- 2876403 TI - Oral manifestations of acquired immunodeficiency syndrome (AIDS) and HTLVIII/LAV infection. PMID- 2876404 TI - [Phimosis and cryptorchism--diagnosis and therapy]. PMID- 2876405 TI - [Experience with sulphasalazine (salazopyrin) in the treatment of rheumatoid arthritis]. PMID- 2876406 TI - Medication management in patients with chronic non-malignant pain. A review of the use of a drug withdrawal protocol. AB - One hundred and twenty-four (71%) of 173 patients, admitted consecutively to the Inpatient Service of the University of Washington Multidisciplinary Pain Center, were consuming narcotic/sedative drugs and 49 (29%) were not. We describe the use of a drug withdrawal protocol entailing outpatient drug consumption diaries; a 48 h inpatient drug profile; the use of drug equivalence tables to convert drugs consumed to a methadone/phenobarbital pain cocktail and the subsequent tapering of the active contents of the pain cocktail. Diaries reliably revealed the types of drug consumed but not extent of consumption. Narcotic consumption in particular tends to be underreported. For patients with a history of a drug problem and those who consume narcotics heavily during the first day of profile, a 48 h profile is appropriate. In others a 24 h profile is safe. Objective signs of excessive consumption or a withdrawal syndrome were noted in 2 patients during the profile period and in 4 patients during the taper from pain cocktail. Published tables appear to give a reasonable estimate of drug equivalence. The importance of monitoring patients during the protocol is emphasized. PMID- 2876407 TI - [HLA and multiple sclerosis]. AB - Etiology of and pathogenetic mechanisms in multiple sclerosis are still badly known; therapy is thus uncertain and poorly active. Many recent studies have nevertheless shown a weak but clear association with HLA-DR2, as the possible role of a HTLV-related virus. Infection of genetically sensitive (DR2 positive) children would induce an auto-immune disease with a cellular and humoral reactivity against myelin antigens. A rather active and certainly harmless treatment consists in administration of immunoglobulins. PMID- 2876409 TI - The use of biotinylated hybridization probes for routine analysis of unique sequences in human DNA. PMID- 2876408 TI - Vasculitis. AB - Inflammatory changes in blood vessels are a prominent feature of several diseases, which can be categorized by the size of the vessels, the nature of the inflammatory exudate, and the specific organs involved. The clinical and laboratory findings are variable and frequently nonspecific. Therapy ranges from essentially just observation to high-dose steroids combined with immunosuppressive agents, but treatment must be individualized. Early and correct diagnosis is thus important, but because there is considerable overlap between diseases, especially in the leukocytoclastic vasculitis group, one should never delay initiation of therapy while one is trying to finalize the diagnosis, particularly when the patient may be deteriorating rapidly. PMID- 2876410 TI - RFLPs for the human apolipoprotein B gene: HincII and PvuII. PMID- 2876411 TI - RFLPs for transforming growth factor alpha (TGFA) gene at 2p13. PMID- 2876412 TI - pHW60, an anonymous single copy clone from the proximal portion of the long arm of chromosome 19 (HGM8 assignment no. D19S13). PMID- 2876413 TI - BglII polymorphic site downstream to the human apolipoprotein AIV (apoAIV) gene. PMID- 2876414 TI - A polymorphic Xba I site within the human von Willebrand factor (vWF) gene identified by a vWF cDNA clone. PMID- 2876415 TI - Simultaneous infection with Bordetella pertussis and respiratory syncytial virus in hospitalized children. AB - We compared three groups of hospitalized children with Bordetella pertussis infection, respiratory syncytial virus (RSV) infection and dual B. pertussis/RSV infections in an effort to establish clinical and laboratory criteria by which to distinguish children with dual infections from children infected with either organism alone. The groups were compared for admission laboratory data, history of present illness, perinatal history and immunization history. Children with pertussis were more likely to have been premature (less than 37 weeks gestation) than children with RSV infections only (11 of 29 vs. 1 of 22, chi square test, 5.94, P less than 0.02). Other than B. pertussis and RSV fluorescent antibody testing and culture, there were no laboratory or clinical criteria by which to differentiate these children consistently at the time of hospital admission. For purposes of medical management and infection control, pertussis or simultaneous infection with pertussis should be considered in young children hospitalized for presumed viral respiratory illness. PMID- 2876416 TI - Neuropeptide Y is an inhibitor of neural function in the myenteric plexus of the guinea-pig ileum. AB - Neuropeptide Y (NPY) reduced the resting tension of the myenteric plexus longitudinal muscle preparation (MP-LM) of the guinea-pig ileum (GPI). NPY in a dose-dependent manner also reduced the neurally-mediated excitatory effect of cholecystokinin octapeptide (CCK8) sulfated form on this preparation. However, NPY, at the concentration used in the study, did not modify the effect of exogenous acetylcholine (ACh). All these features were also shared by other inhibitory peptides, like somatostatin (SOM) and the enkephalin derivative FK 33 824. The preparation developed a degree of tachyphylaxis to the inhibitory effect of NPY more rapidly than it did to SOM. Moreover, the inhibitory effect of neuropeptide Y was of longer duration than the one seen for somatostatin. A faster metabolic rate might account for the lower development of tachyphylaxis to somatostatin. The presence of the opioid antagonist naloxone did not alter the inhibitory features of NPY or SOM. Therefore, the involvement of any endogenous opioid in the action of these two inhibitory peptides can be disregarded. PMID- 2876417 TI - [Serum gamma-glutamyltransferase activity and molecular polymorphism in persons exposed to substances in the petrochemical industry]. PMID- 2876418 TI - Intrauterine aplastic anemia and fetal hydrops: a case report. AB - Fetal hydrops developed in the 8-day interval between two ultrasonographic examinations of a pregnant woman who had presented with a revealed placental abruption. Chronic ulcerative colitis had been treated with oral prednisone and sulfasalazine until the second month of pregnancy and then with prednisone only. An autolysed hydropic fetus was delivered at 26 weeks gestation. No hematopoietic tissue was identified in the small pale fetal liver, in the bone marrow, or in other organs. No cause for hydrops other than the aplastic anemia was identified. PMID- 2876419 TI - [Detection by scintigraphy with meta-iodobenzylguanidine of a subclinical tumoral thyroid nodule in Sipple's syndrome]. PMID- 2876420 TI - [Properties of (Ala5, Orn9)-somatostatin. The inhibition of pancreatic and hypophyseal hormone secretion in cell culture]. AB - Ability of Ala5, Orn9-somatostatin to inhibit the secretion of insulin, glucagon, somatotropic hormone (STH) and prolactin was tested on the model of primary monolayer culture of isolated insular pancreatic and adenohypophyseal cells. Chemical substitution performed between positions 5 and 9 in somatostatin molecule failed to change essentially hormone's biologic activity in suppression of insulin and glucagon in the culture of pancreatic insular cells isolated from newborn rats. Somatostatin analog revealed its natural hormonal ability to inhibit STH secretion but failed to affect that of prolactin. The results are suggestive of the principal possibility to produce somatostatin biologically active analog through lyzine residue substitution in position 9 with obligatory simultaneous substitution amino acid residue in position 5. PMID- 2876421 TI - Activities in nursing ethics: local, national, international. PMID- 2876422 TI - [Regulatory subpopulations of T lymphocytes in patients with pulmonary tuberculosis]. PMID- 2876423 TI - Strategies for studying heterogeneous genetic traits in humans by using a linkage map of restriction fragment length polymorphisms. AB - Simple single-gene disorders in humans can be genetically mapped by using traditional methods of linkage analysis and increasingly abundant restriction fragment length polymorphisms (RFLPs). Many human diseases and traits, however, can be expected to be genetically heterogeneous (i.e., caused by any one of several genes), and traditional linkage analysis is much less effective in such circumstances. We present two methods, interval mapping and simultaneous search, designed to exploit the full power of a linkage map of the DNA markers. For the simplest situations, only 1/3 as many affected families are needed to map a heterogeneous trait by using these methods. Only 1/5-1/50 as many are needed to detect that genetic heterogeneity is present. PMID- 2876424 TI - Genetic linkage between the antigenic group (Ag) variation and the apolipoprotein B gene: assignment of the Ag locus. AB - The antigenic group (Ag) system of homospecific human serum antigens of low density lipoprotein is detected by antiserum from multiply transfused patients. A complex series of common Ag alleles has been described, but the biochemical nature of this polymorphism is uncertain. Here we report that DNA polymorphisms at the human apolipoprotein B (apoB) locus are very closely linked to alleles of the Ag system. We also show a strong association between Ag(x) and a polymorphism detected with the restriction endonuclease Xba I. We conclude that the immunologically determined Ag system represents protein polymorphism of apoB rather than primary genetic differences in posttranslational processing or lipid binding. These studies therefore demonstrate that the Ag locus is located on the short arm of human chromosome 2 in the region p23-p24 to which the apoB gene has been assigned. Since the Ag(x) antigen is associated with altered plasma lipid levels, this determinant may indicate a functionally important domain of apoB. PMID- 2876425 TI - Molecular detection of deletions involving band q14 of chromosome 13 in retinoblastomas. AB - DNA fragments from a locus spanning 29 kilobases within chromosome band 13q14 detected deletions in 3 retinoblastomas out of 37 such tumors examined. Somatically occurring, homozygous deletions spanning at least 25 kilobases were detected in retinoblastomas from two unrelated patients. These deletions are bounded by the esterase D locus proximally. In a third patient, both tumor cells and leukocytes have a deletion of one chromosome 13 homolog, with one end of the deletion localized to a 1.55-kilobase fragment within the cloned region. It is likely that the cloned locus is within a few hundred kilobases of the retinoblastoma gene (i.e., the locus governing predisposition to such tumors) and that the deletions detected also involve the retinoblastoma gene. Further, it may be possible to base a successful approach to the isolation of the retinoblastoma gene on this assumed physical proximity of the two loci. PMID- 2876426 TI - Polymorphisms in the human haptoglobin gene cluster: chromosomes with multiple haptoglobin-related (Hpr) genes. AB - We have found polymorphisms for the number of tandemly arranged haptoglobin related (Hpr) genes in the haptoglobin gene cluster of Blacks. Genomic mapping and nucleotide sequence analysis indicate that two copies of the Hpr gene first resulted from unequal but homologous crossing-over in a region 3' to the haptoglobin (Hp) and the haptoglobin-related genes. Subsequent increases in the number of Hpr loci have occurred in some chromosomes. Among 25 American Blacks studied (15 were unrelated), 2 related individuals have one extra copy of the Hpr gene and 5 unrelated individuals have more than two extra Hpr genes. None of 26 Whites and one Oriental studied have extra copies. In one of the Blacks, six tandemly arranged Hpr genes were demonstrated in one chromosome by pulsed field gradient electrophoresis. His other chromosome had one Hpr gene. The tandem Hpr genes were found in individuals with the haptoglobin genotypes Hp2/Hp2 (3 of 3 tested) and Hp2/Hp1 (4 of 11 tested), but none were found in the Hp1/Hp1 individuals (11 tested). Fibroblast cell cultures from two Hp2/Hp1 heterozygotes were fused to mouse cells to obtain cell lines retaining a human chromosome 16 on which the haptoglobin gene cluster is located. DNA analysis of the hybrid cells showed that in both individuals the tandemly arranged Hpr genes are linked to the Hp2 allele. These results suggest that the multiple copies are associated with the Hp2 gene. PMID- 2876427 TI - Tyrosine hydroxylase is expressed by neocortical neurons after transplantation. AB - Tyrosine hydroxylase [TyrOHase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2], an essential enzyme in the synthesis of catecholamines, is expressed normally by neurons in the brainstem but not by those in mature neocortex. When embryonic neocortex is transplanted into adult neocortex, TyrOHase-immunoreactive cells develop and continue to be present in the transplants for the life of the host animal. The percentage of transplant neurons that express TyrOHase is highly correlated with the age of the embryonic donor tissue at the time of transplantation. Many TyrOHase immunoreactive cells are present in transplants from embryonic day 12 (E12) embryos. The labeled cells are frequently arrayed in striking clusters of cell bodies and their processes, which ramify densely within the transplants. Moderate numbers of cells are found scattered throughout transplants from E14 donors, while E17 donors consistently develop small numbers of TyrOHase-containing cells. Tissue removed for transplantation on the day before birth (E19) never contains cells that express TyrOHase. The TyrOHase-positive cells are mostly bipolar and stellate in shape and show neither immunoreactivity for other catecholamine synthesizing enzymes nor catecholamine fluorescence. These results provide a demonstration of continued TyrOHase synthesis in central nervous system cells that normally do not express this enzyme. Because of these and similar results with other neurotransmitter enzymes, the transplantation paradigm is particularly useful as a technique for studying the factors that regulate enzyme induction and activity during development of the nervous system. PMID- 2876428 TI - Somatostatin selectively enhances acetylcholine-induced excitations in rat hippocampus and cortex. AB - The neuronal effects of somatostatin-14 (SS-14) and its influence on responses to acetylcholine (AcCho) were studied in vivo in the rat parietal cortex and dorsal hippocampus, using single-unit recording and microiontophoresis. SS-14 inhibited spontaneous firing of nearly all cells tested, while AcCho facilitated their firing. In contrast to its direct slowing effect, sustained iontophoretic application of SS-14 enhanced AcCho-induced excitations in 78% of all cells tested. This AcCho-enhancing effect of SS-14 was dose dependent. SS-14 did not enhance the responsiveness to pulses of the excitatory amino acid glutamate. Neurons tonically driven by iontophoretic currents of AcCho responded to concurrent pulses of SS-14 with an increase in firing. Thus, iontophoretic application of SS-14 can produce qualitatively different effects on the spontaneous activity of its target cells depending on the simultaneous effects of other chemical messengers. These condition-dependent interactions may explain the diverse neuronal effects of SS-14 reported in the literature. PMID- 2876429 TI - Amino acid sequence of the plasma membrane ATPase of Neurospora crassa: deduction from genomic and cDNA sequences. AB - The plasma membrane of Neurospora crassa contains an electrogenic H+-ATPase (EC 3.6.1.35), for which we have isolated and sequenced both genomic and cDNA clones. The ATPase gene is interrupted by four small introns (58-124 base pairs). It encodes a protein of 920 amino acids (Mr, 99,886) possessing as many as eight transmembrane segments. The Neurospora ATPase shows significant amino acid sequence homology with the Na+,K+- and Ca2+-transporting ATPases of animal cells, particularly in regions that appear to be involved in ATP binding and hydrolysis. PMID- 2876431 TI - Substance B: an endogenous brain factor that reverses presynaptic inhibition of acetylcholine release. AB - Evidence is presented of the existence of a substance in brain (substance B) that reverses presynaptic inhibition of evoked acetylcholine (AcCho) release. Addition of guinea pig brain synaptosomal incubation medium or whole brain extracts to assays in which 1,1-dimethyl-4-phenylpiperazinium-evoked release of [3H]AcCho from guinea pig myenteric plexus synaptosomes reversed purinergic, muscarinic, and alpha 2-adrenergic agonist inhibition. However, the extracts did not increase basal or evoked release of AcCho. Results of chromatography on Bio-Gel P-2 of a concentrated whole brain extract suggest this factor has an Mr of 700. Substance B was resistant to boiling under acid or alkaline conditions as well as incubation with phospholipase C and various proteases; ashing, however, completely destroyed activity. This endogenous factor was also found to antagonize agonist-mediated inhibition of electrically evoked contractions of myenteric plexus-longitudinal muscle strips from the guinea pig ileum. The demonstration of substance B with its ability to reverse presynaptic inhibition of AcCho release reveals one mode of presynaptic modulation. PMID- 2876430 TI - Human triose-phosphate isomerase deficiency: a single amino acid substitution results in a thermolabile enzyme. AB - Triose-phosphate isomerase (TPI; D-glyceraldehyde-3-phosphate ketol-isomerase, EC 5.3.1.1) deficiency is a recessive disorder that results in hemolytic anemia and neuromuscular dysfunction. To determine the molecular basis of this disorder, a TPI allele from two unrelated patients homozygous for TPI deficiency was compared with an allele from a normal individual. Each disease-associated sequence harbors a G X C----C X G transversion in the codon for amino acid-104 and specifies a structurally altered protein in which a glutamate residue is replaced by an aspartate residue. The importance of glutamate-104 to enzyme structure and function is implicated by its conservation in the TPI protein of all species that have been characterized to date. The glutamate-to-aspartate substitution results in a thermolabile enzyme as demonstrated by assays of TPI activity in cultured fibroblasts of each patient and cultured Chinese hamster ovary (CHO) cells that were stably transformed with the mutant alleles. Although this substitution conserves the overall charge of amino acid-104, the x-ray crystal structure of chicken TPI indicates that the loss of a side-chain methylene group (-CH2CH2COO- --- -CH2COO-) is sufficient to disrupt the counterbalancing of charges that normally exists within a hydrophobic pocket of the native enzyme. PMID- 2876432 TI - The Florey lecture, 1986. The regulatory biology of antibody formation. AB - The regulatory biology of antibody formation entered a new phase of study with the development of selective theories of immunity. The discovery of the 'one cell - one antibody' dogma and the demonstration that only a small minority of B cells possessed receptors specific for a given antigen were consistent with Burnet's clonal selection hypothesis, which was later formally proven by preparing antigen specific lymphocytes and inducing clonal activation in vitro. Clonal analysis has aided precise study of immunoregulation for both B and T lymphocytes. Clonal activation of B cells in the absence of T cells is now possible with high cloning efficiency. It requires the combined action of certain antigens and growth factors, collectively termed B-cell stimulatory factors (BSFS). Single cell analysis has shown that most BSFS so far tested, in contrast to most claims in the literature, possess the capacity (in synergy with antigen) to: stimulate B cells out of the G0 phase into active cell cycle; promote sequential mitotic divisions; and induce differentiation to active secretory status. This is clearly true for IL-1, IL-2, and BSF-p2. These multiple actions resemble those of the colony-stimulating factors in haemopoiesis. Regulation of antibody production by T lymphocytes can also be profitably analysed in clonal systems. The immunoregulatory problem of tolerance can also be analysed by means of clonal techniques. Studies are summarized which indicate that T-cell-mediated suppression and functional silencing of toleragen-specific lymphocytes are both cooperatively involved in many tolerance models. For the B lymphocyte, tolerance can be induced without an actual deletion of the cell involved; rather, the tolerant cell appears to have received and stored a negative signal, rendering it unresponsive to normally immunogenic stimuli. Thus, a state termed 'clonal anergy' has been induced within the cell. Functional clonal deletion has also been noted in several models to T-lymphocyte tolerance, but here it is not known whether clonal anergy or actual death of the relevant cell is at work. Self tolerance sufficient to be consistent with good health need not mean a total absence of cells with any degree of self-reactivity. Indeed, it is clear that some B cells capable of forming antibody with some degree of affinity for self constituents exist in the body, and can be activated, for example by lipopolysaccharide. The requirement is to limit the amount, affinity and duration of autoantibody production. A model suggesting how this may be achieved is presented. PMID- 2876433 TI - Panum's phenomenon and the confluence of signals from the two eyes in stereoscopy. AB - The signals from the two eyes must be routed to allow either eye to have access to the processing mechanisms for position, shape, colour, etc.; at the same time, information as to the eye of origin must be retained for the purposes of stereoscopy. The study of this confluence of signals from the two eyes was approached psychophysically by studying induced position and depth changes of adjacent binocular and monocular stimuli in the human fovea. It was demonstrated that a monocular visual stimulus located near a binocular one acquires a depth signal, according to a scheme originally proposed by Panum. The effect is unspecific as regards feature shape and brightness, and falls off with a length constant of about 15 minutes of arc in the fovea. A monocular stimulus also affects the apparent depth of its binocular neighbour in a centre-surround manner; disparity pooling changes to disparity repulsion when features are separated by distances of about 3 minutes of arc in the fovea. The findings led to the development of a scheme of uniocular connectivity to a matrix of depth units. Excitation patterns here would depend on the state of the input lines, the intrinsic neuronal interaction properties, and contextural configuring influences from other parts of the nervous system. Experiments showing the spatial extent of pooling and repulsive interaction within the disparity domain help to characterize the stimulus processing in this neural ensemble. PMID- 2876436 TI - Analgesic effectiveness of topically applied dynorphin on human dental pulp. PMID- 2876435 TI - Stimulant action of ethanol on posttetanic potentiation of hindlimb monosynaptic reflexes. PMID- 2876434 TI - Capsaicin-induced beta-adrenergic action on energy metabolism in rats: influence of capsaicin on oxygen consumption, the respiratory quotient, and substrate utilization. AB - The mode of action of capsaicin on energy metabolism was investigated in rats. The oxygen consumption was higher when capsaicin (6.0 mg/kg) was intraperitoneally injected than when it was not injected. The respiratory quotient (R.Q.) increased and then decreased after the administration of capsaicin. The levels of serum glucose and immunoreactive insulin rapidly increased after the administration of capsaicin. Also, liver glycogen rapidly decreased, in contrast to the serum glucose concentration which rapidly increased. The serum-free fatty acid level gradually increased after the administration of capsaicin. These alterations in energy metabolism on the administration of capsaicin were similar to those in the metabolism of epinephrine, and were specifically inhibited by various beta-adrenergic blockers. On the other hand, the alterations were not affected by pretreatment with alpha adrenergic or ganglion blockers. These results suggest that the mode of action of capsaicin on the enhancement of energy metabolism in rats comprises a direct (as an agonist) and/or an indirect (via catecholamine) beta-adrenergic action. Therefore, it was speculated that the adrenergic action of capsaicin resulted, at least in part, in a decrease in the perirenal adipose tissue weight and serum triglyceride concentration in rats fed a high fat diet supplemented with capsaicin (T. Kawada et al., J Nutr 116:1272-1278, 1986). PMID- 2876437 TI - The modulation of generation/function of human cytotoxic lymphocytes by autacoids: unusually compartmentalized cAMP? PMID- 2876438 TI - Functional antagonism of isoprenaline, salmefamol, fenoterol and pindolol by carbachol, methacholine and histamine in guinea pig isolated trachealis. PMID- 2876440 TI - Autonomic changes elicited by chemical stimulation of mediodorsal nucleus of the thalamus. AB - Chronic indwelling cannulas were implanted in the mediodorsal nucleus (MD) of the thalamus in New Zealand albino rabbits. Heart rate (HR), blood pressure (BP), respiration and electromyographic activity (EMG) were recorded subsequent to the injection of saline, l-glutamate, or carbachol through the previously implanted cannulas. Dose related decreases in HR and increases in BP were obtained after administration of both l-glutamate and carbachol at doses in the micromolar range. Control injections through cannulas chronically implanted in the overlying hippocampus or adjacent ventricles resulted in dramatic HR and BP baseline changes in a parasympathetic direction (viz HR and BP decreases) suggesting that the effects obtained with MD placements were due to chemical stimulation of MD. Responses elicited from MD in the present experiment were similar, but not identical, to those produced by electrical stimulation of MD, suggesting that the latter effects were not due to stimulation of fibers of passage. PMID- 2876439 TI - The antianxiety effect of beta-blockers on punished responding. AB - Clinically effective anxiolytic drugs generally increase responding that is suppressed by punishment. Although beta-adrenergic antagonists have been reported to reduce anxiety in humans, such effects have not been reported reliably in animal punishment procedures. In the present study, three pigeons were trained to key peck under a multiple schedule. In the presence of a white light every thirtieth response produced grain. In the presence of a red light every thirtieth response produced grain and electric shock which suppressed responding to approximately 10 percent of that occurring in the alternate component. Propranolol (1.0-5.6 mg/kg) and, less reliably, atenolol significantly increased punished responding in a dose-related manner; propranolol effects were approximately twice as large as those of atenolol. Both drugs no more than weakly increased unpunished response rates at doses that increased punished responding. These results suggest that beta-blockers have an antianxiety effect on punished behavior, and that peripheral beta-blockade, the predominant action of beta blockers regardless of whether they readily penetrate the brain, is likely to be involved in this effect. PMID- 2876441 TI - Effects of neuroleptic drugs on the inhibition of exploratory behaviour induced by a low dose of apomorphine: implications for the identity of dopamine receptors. AB - Apomorphine in low doses inhibits spontaneous exploratory behaviour in rats. This effect is commonly referred to as an expression of selective stimulation of dopaminergic autoreceptors. The aim of the present study was to investigate the influence of neuroleptic drugs with different pharmacological profiles on this apomorphine induced inhibition of exploration using techniques for detailed recording of behaviour and multivariate statistical analysis of the results. By comparison with dose response analyses of apomorphine it was possible to determine whether a neuroleptic specifically antagonised the apomorphine effect or if the pattern of behaviour was qualitatively changed in some way. Apomorphine (0.05 mg/kg) was tested against cis-flupenthixol (0.01-0.5 mg/kg), haloperidol (0.01-0.1 mg/kg), metoclopramide (0.2-5 mg-kg), sulpiride (0.5-50 mg/kg) and SCH 23390 (0.005-0.05 mg/kg). Metoclopramide and haloperidol had weak antagonising effects against apomorphine while cis-flupenthixol and SCH 23390 was completely inefficient in this respect. The multivariate analysis indicated that the effects of haloperidol was restricted to only some aspects of the behavioural effects of apomorphine. Only sulpiride did selectively and dose-dependently antagonise the apomorphine induced behavioural suppression. The data provide evidence for a functional subdivision of dopamine receptors at the behavioural level. PMID- 2876442 TI - Interaction of famotidine with rat liver microsomes, a study showing less inhibition of drug metabolism than with cimetidine. AB - Interaction of famotidine with rat liver microsomes and its effect on drug metabolism in vitro were studied. Famotidine interacted with liver microsomes obtained from untreated, phenobarbital-pretreated and 3-methylcholanthrene pretreated rats to produce characteristic type II spectral changes with peaks at 423-426 nm and troughs at 387-390 nm. The spectral dissociation constants were in the range of 0.84-0.94 mM. Famotidine inhibited aminopyrine N-demethylase activity to a much lesser extent than did cimetidine. The extent of inhibition at a concentration of 5 mM of famotidine was from 12 to 18% for the microsomes from the rats with different pretreatments. In contrast, 5 mM of cimetidine inhibited the activity 80, 59 and 80% in the microsomes from untreated, phenobarbital pretreated and 3-methylcholanthrene-pretreated rats, respectively. Both famotidine and cimetidine inhibited aminopyrine N-demethylase in a mixed-type manner for the microsomes from phenobarbital-pretreated rats, with inhibition constants of 4.7 and 0.7 mM, respectively. These results demonstrate that famotidine is an in vitro inhibitor of microsomal drug metabolism in rats but is much less inhibitory than cimetidine. PMID- 2876444 TI - [Interaction between macromolecular adjuvants and drugs. 24. Improvement of the solubility characteristics of benzodiazepine derivatives with polyvinylpyrrolidone]. AB - Solubility and dissolution rate of the benzodiazepine derivatives chlordiazepoxide, diazepam, medazepam, nitrazepam and clonazepam has been improved by adding polyvinylpyrrolidone (PVP K 30). Increasing concentrations of the carrier as well as the preparation of coprecipitates usually supported the effect (less physical mixtures). Regarding to the dissolution PVP has a positive effect on the initial phase of dissolution particularly. Under the experimental conditions described an interaction between drugs and carrier was revealed increasing with the concentration of PVP. These interactions were of endothermic character. Connections between dissolution and binding results were evident. Differential thermal analysis and x-ray diffractometric studies probably refer to a partial amorphous form of the drugs, especially in coprecipitates with a higher concentration of PVP. PMID- 2876443 TI - 6-Aminonicotinamide: EEG changes and effects on the activities of enzymes related to glutamate metabolism in rat brain regions. AB - 6-Aminonicotinamide (6-AN), an antimetabolite of pyridine nucleotide synthesis, caused time dependent and regionally selective changes in the activities of the enzymes related to glutamate metabolism in the brain. The NAD+- and NADP+-linked glutamate dehydrogenase showed opposite pattern of changes in cerebellum, whereas cerebral hemispheres and brain stem exhibited similar response. Glutamate oxaloacetate transaminase (aspartate aminotransferase) and malate dehydrogenase, the functional enzymes of malate-aspartate shuttle, were decreased in soluble fraction of cerebral hemispheres and increased significantly in cerebellum after 16 hours of drug administration. Glutamate pyruvate transaminase (alanine aminotransferase) also showed an increase in the activity in cerebellum and brain stem after 8 hours of drug treatment. The EEG patterns obtained from 6-AN treated animals showed periodic bursts, turning to convulsive polyspike activity between 8-16 hours, indicating the onset of comatose-like stage. The results indicate that glutamate metabolism offers considerable anaplerotic potentials following impaired energy state after 6-AN treatment. PMID- 2876445 TI - Neuroanatomical, neuropharmacological and neurobiochemical target systems for antipsychotic activity of neuroleptics. PMID- 2876446 TI - Stress-induced analgesia: adaptive pain suppression. AB - In this paper we have examined the phenomenon of stress-induced analgesia. We have described the procedures used to measure analgesia and have suggested that the tests can be designed not only to indicate changes in pain threshold but also to allow for the determination of the capacity to execute adaptive behavior. Aside from enabling the analysis of responses, tests that induce reflexive as well as nonreflexive behavior may have the capacity to separate the more complex aspects of pain such as the possible presence of two components of pain, sensory/discriminative and motivational/affective. These components may be of fundamental importance for any attempt to understand the biological significance of SIA. Our examination of the neurotransmitter and neuropeptide systems has revealed that they are affected by the same manipulations that induce SIA. These amines and perhaps peptides play an integral role in learning, motivation, and performance. We conclude that the functional advantage of a reduction of pain during stressful situations is significant because it allows the animal to react in threatening and perhaps critical situations as if there were no pain. Once the pain system is inhibited, other systems modulate and mediate adaptive responses that expedite the survival of the animal. PMID- 2876447 TI - In vitro amoebicidal testing of natural products; Part I. Methodology. PMID- 2876448 TI - Management of foot injuries with free-muscle flaps. AB - Transfer of a free-muscle graft with application of a split-thickness skin graft is one of many techniques available for reconstruction of the massive foot injury. The durability of such a reconstruction has been questioned. We have treated nine patients suffering from foot injuries with extensive soft-tissue loss. Each patient underwent reconstruction using a free-muscle transfer covered by a split-thickness skin graft. A mean follow-up of 33 months (range 17 to 48 months) is reported for these nine patients. Each patient is ambulatory. One patient developed an ulcer on the plantar surface, which was treated successfully by flap revision and skin grafting. We feel this technique provides a durable reconstruction for significant soft-tissue loss of the foot. PMID- 2876449 TI - Tardive dyskinesia: natural history studies assist the pursuit of preventive therapies. PMID- 2876450 TI - Intrastriatal injection of DL-2-amino-5-phosphonovaleric acid (AP-5) induces sniffing stereotypy that is antagonized by haloperidol and clozapine. AB - DL-2-amino-5-phosphonovaleric acid (AP-5), which blocks glutamatergic transmission at the NMDA-preferring receptor, was injected into the antero-dorsal striatum of rats. AP-5-induced behavioural changes were assessed i) using a stereotypy rating scale and ii) using an experimental chamber designed to quantify sniffing. In both behavioural situations it was shown that AP-5 (10 micrograms/0.5 microliter) induced continuous intensive sniffing similar to that induced by small doses of systemically administered amphetamine or apomorphine. However, oral stereotypies were not induced by AP-5. Systemically injected clozapine (5 and 10 mg/kg SC) as well as haloperidol (0.1 mg/kg IP) antagonized AP-5-induced sniffing. These results show that besides dopamine receptors, NMDA receptors are involved in the control of sniffing. In behavioural terms, the effect of glutamate mediated by the NMDA receptor in the striatum is opposite to that of dopamine. PMID- 2876452 TI - Neuroleptic reduction of cocaine-induced paranoia but not euphoria? AB - Central dopaminergic activation is hypothesized to underly schizophrenia and, paradoxically, stimulant euphoria. Four cocaine abusers with histories of stimulant-induced paranoid psychoses reported selective reduction in psychotic symptoms but not euphoria when treated with dopamine blockers. This provides preliminary evidence against efficacy of neuroleptics in cocaine abuse prevention, and suggests euphoria and paranoia may have discriminable neurophysiological substrates. PMID- 2876451 TI - Citalopram: clinical effect profile in comparison with clomipramine. A controlled multicenter study. Danish University Antidepressant Group. AB - The selective serotonin reuptake inhibitor citalopram was compared with clomipramine in a multicenter clinical study. From a total of 150 depressed patients (age 18-65 years), 114 patients with a Hamilton Depression Scale (HDS) total score greater than or equal to 18 at the end of a 1 week placebo period were started on treatment with either citalopram (40 mg/day) or clomipramine (150 mg/day) (fixed, single daily dose). Patients stratified according to diagnostic rating (Newcastle Inventory, endogenous/non-endogenous) were randomly allocated to treatment groups using double blind principles. In total, 102 patients completed more than 2 weeks, treatment and were included in the analyses of therapeutic effect. The two drug groups were comparable in terms of sex, age, and departmental distribution. Categorical measurements of therapeutic effect based on the HDS total score showed that in the endogenously depressed patients a significantly higher percentage of patients on clomipramine (n = 37) than on citalopram (n = 38) were classified as complete responders (HDS total less than or equal to 7) after 3, 4 and 5 weeks of treatment. In the non-endogenously depressed patients (clomipramine: n = 15, citalopram: n = 12) rather similar numerical differences were observed (P less than 0.05 at 5th week). In the total patient group the percentage of complete response after 5 weeks was about 60 in the clomipramine group (n = 52) and about 30 in the citalopram group (n = 50) (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876454 TI - Treatment length in post-traumatic stress disorder. PMID- 2876455 TI - Alteration of lactase and aminopeptidase N expression in porcine enterocytes by energy intake and environment. AB - The influence of nutrition, environmental temperature and time of feeding on lactase and aminopeptidase N activities in enterocytes of young pigs has been investigated. Animals were kept in the cold (10 degrees C) or warm (35 degrees C) and given either a high or low energy intake. In animals from the cold, lactase activity as determined by scanning microdensitometry was significantly lower at 4 h after a meal than it was in animals from the warm. At 6 h, the activities were similar in all groups, while at 20-24 h after feeding, lactase activity was much greater in those kept at 10 degrees C than in those at 35 degrees C. Level of energy intake had no statistically significant effect and no differences were found with respect to aminopeptidase N. The possibility that these differences in lactase activity are related to thyroid hormone metabolism and energy supply in relation to demand is discussed. PMID- 2876453 TI - Behavioral differentiation between pharmacokinetic and pharmacodynamic components of the interaction of antidepressants or neuroleptics with methamphetamine. AB - This study proposes a method capable of separating the pharmacodynamic from the pharmacokinetic component in the methamphetamine (MA) hyperactivity potentiation induced by antidepressants. Several antidepressants and neuroleptics, other centrally-acting drugs and the inhibitor of hepatic drug metabolism SKF 525-A were studied. The motility counts taken between 10 and 20 min after MA injection were considered as an index of pharmacodynamic interaction and the whole duration of the hyperactivity syndrome as an index of pharmacokinetic interaction. The duration of MA effect was prolonged by some of the drugs studied and left unchanged by the others regardless of their clinical classification. On the contrary, our evaluation of the intensity of MA effect produced a sharp differentiation between classical neuroleptics and typical antidepressants: the former antagonized and the latter potentiated MA peak intensity. Only the D-2 blocking neuroleptics sulpiride and tiapride potentiated MA intensity. Regarding the specificity of our model, none of the compounds known to be devoid of clinical antidepressant or antipsychotic activity interacted with MA in such a way as to be included in either category. As to the sensitivity of the test, two "false negatives" were obtained: the neuroleptic clozapine and the antidepressant mianserin. Such exceptions were discussed taking into account their peculiar mechanisms of action. PMID- 2876456 TI - Ulcerative colitis in West Indian immigrants. AB - Over a 15-year period six patients (five female) of Afro-Caribbean origin presented with ulcerative colitis from a community of this ethnic extraction numbering 47,000 persons. The disease was characterised by an acute severe presentation, extensively affected bowel, an active course of disease and a propensity for severe hypersensitive reactions to oral sulphasalazine. These findings are of particular implication in the management of ulcerative colitis in West Indians. PMID- 2876457 TI - Postural hypotension--pathophysiology and management. PMID- 2876458 TI - [Technical advances in the preparation of a solder between a Co-Cr-Mo alloy and a precious metal]. PMID- 2876459 TI - Takayasu arteritis: radiographic and angiographic findings in 59 patients. AB - Fifty-nine patients (57 females, two males) with Takayasu arteritis were retrospectively evaluated. Chest radiographs were abnormal in 68% of patients in whom they were obtained (n = 49). Aortic contour changes and calcification were frequent findings. Sixty-eight percent of patients who underwent total aortography (n = 50) had panaortitis, and 28% had involvement confined to the thoracic aorta and/or its branches. Stenosis was the most common angiographic finding in the aorta and its branches, but occlusion (n = 4), aneurysm (n = 3), and dilatation (n = 15) were not infrequent. Adventitial vascular structures (the vasa vasorum) were seen in three cases. Eighty-six percent (n = 21) of pulmonary arteriograms showed abnormalities. Occlusion was by far the most common finding. There was no predilection for any lobe nor correlation with systemic arteritis. It was concluded that Takayasu arteritis characteristically involves the systemic and the pulmonary arteries independently. Total aortography and pulmonary arteriography are necessary to diagnose and evaluate the extent of the disease. PMID- 2876460 TI - Interventional radiology: challenges and initiatives. PMID- 2876461 TI - How can you help all those frightened patients? PMID- 2876462 TI - Carbamylcholine, but not somatostatin or neurotensin, stimulates prostaglandin E2 release from the isolated perfused rat stomach. AB - Prostaglandin E2 release by carbamylcholine (10(-6) M), somatostatin (10(-10)-10( 8) M) and neurotensin (10(-10) - 10(-8) M) has been evaluated in the isolated perfused rat stomach. Carbamylcholine significantly stimulated gastric PGE2 release and increased the perfusion pressure, whereas somatostatin and neurotensin had no effect. Combination of carbamylcholine with somatostatin or neurotensin produced no increase over that found with carbamylcholine alone. The relationship between perfusion-pressure and PGE2 release was not causal. The present findings do not support a role for prostaglandins in the mechanism of somatostatin or neurotensin action in the stomach. PMID- 2876463 TI - [Radiological aspects of multiple endocrine neoplasms (MEN), type 3 or 2B]. PMID- 2876464 TI - [Diseases caused by immune complexes associated with hepatitis B virus]. PMID- 2876465 TI - [A thyroid nodule presenting diagnostic difficulty]. PMID- 2876466 TI - [Anesthetic model in orthotopic transplant of the liver in the pig]. PMID- 2876467 TI - [Determination of ischemia threshold in angina pectoris and its therapeutic usefulness]. PMID- 2876468 TI - Chemotherapy and chemoprophylaxis of hepatic coccidiosis with sulphadimethoxine and pyrimethamine. AB - The activity of a mixture of sulphadimethoxine and pyrimethamine (10:3) as prophylactic medication and prophylactic and therapeutic medication was studied in rabbits experimentally infected with Eimeria stiedai. The haematocrit index (packed cell volume) and haemoglobin levels were studied for assessment of drug toxicity. The activity in serum of aspartate aminotransferase (AST) and alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase were studied as indicators of hepatic lesions. Parasite development was followed on the basis of the presence of oocysts; other parameters were analysed in order to monitor the performance of infected animals. All the parameters studied showed that the chemoprophylactic medication provided efficient control of the infection and of the hepatic lesions. Serum AST activity was seen to be a good indicator of the effect of the drugs on the liver. PMID- 2876469 TI - Interactions between vecuronium and suxamethonium in the dog. AB - The non-depolarising muscle relaxant vecuronium (0.2 mg kg-1) was administered to four dogs. At 50 per cent return of neuromuscular activity, as measured by the train-of-four technique, the depolarising muscle relaxant suxamethonium (0.3 mg kg-1) was injected intravenously. At 50 per cent return of neuromuscular activity reversal of the block was achieved with atropine and neostigmine. The duration of action of suxamethonium was reduced by the prior administration of vecuronium. In the second series of experiments the order of administration of the suxamethonium and vecuronium was reversed. Suxamethonium (0.3 mg kg-1) was administered first and at 50 per cent recovery vecuronium (0.2 mg kg-1) was given. At 50 per cent recovery of the twitch response after vecuronium administration the block was reversed with atropine and neostigmine. The previous administration of suxamethonium prolonged the duration of the vecuronium induced neuromuscular block. PMID- 2876470 TI - [Hemorrhagic fever with renal syndrome: clinical and epidemiologic aspects]. PMID- 2876471 TI - [Treatment of duodenal ulcer with histamine H2 antagonists and alkalies]. PMID- 2876472 TI - [Arterial hypertension in the aged]. PMID- 2876473 TI - [Relation between arterial hypertension and the short- and long-term aspects of clinical development following a 1st myocardial infarction]. PMID- 2876474 TI - [Arterial hypertension and ischemic cardiopathy]. PMID- 2876475 TI - [Prevention of the increase of exertional blood pressure in patients with borderline essential hypertension. Comparative study of the effects of nifedipine and/or propranolol]. PMID- 2876476 TI - [Electrocardiographic, hemodynamic and echocardiographic correlations in young hypertensives during the exercise test]. PMID- 2876477 TI - [Intravenous administration of labetalol in the treatment of hypertensive emergencies]. PMID- 2876478 TI - [Treatment of malignant arterial hypertension with captopril]. PMID- 2876479 TI - [Intraventricular thrombosis and systemic thromboembolism following acute myocardial infarction--retrospective study of 709 patients]. PMID- 2876480 TI - [Anatomo-clinical correlations regarding microcirculation in cicatricial myocardial infarction]. PMID- 2876481 TI - [Recurrent acute myocardial infarction]. PMID- 2876482 TI - [The esophageal electrocardiographic route in the study of atrioventricular conduction]. PMID- 2876483 TI - [Serum zinc and copper in patients with thromboangiitis obliterans of the lower limbs]. PMID- 2876484 TI - [Neural liquid and pain, XVIIth-XVIIIth centuries]. PMID- 2876485 TI - Nocturnal myoclonus: treatment efficacy of clonazepam and temazepam. AB - Clonazepam (1 mg h.s.) and temazepam (30 mg h.s.) were studied in 10 patients diagnosed as having insomnia with nocturnal myoclonus. Each subject underwent two nocturnal polysomnographic recordings while drug-free, two during treatment with clonazepam, and two during treatment with temazepam. Treatment sessions were 7 days long, and recordings were done on nights 6 and 7 of the treatment sessions. A 14-day washout period separated the treatment sessions. The order of drugs used in the first and second treatment sessions was randomized. Objective and subjective sleep laboratory data showed that both drugs improved the sleep of patients with insomnia in association with nocturnal myoclonus. Neither drug significantly reduced the number of nocturnal myoclonic events. Sleep changes were consistent with those produced by sedative benzodiazepines in general. Thus, the data support clinical reports that clonazepam, a benzodiazepine marketed for the indication of seizure, is useful in improving sleep disturbances associated with nocturnal myoclonus. Temazepam, a benzodiazepine marketed for the indication of insomnia, was found to be a suitable alternative to clonazepam in the treatment of insomnia associated with nocturnal myoclonus. The present data and other studies suggest the need for a model that explains why leg movements and sleep disturbances may wax and wane independently. PMID- 2876486 TI - [Therapeutic aspects of infantile asthma. Part I]. PMID- 2876487 TI - [The menopause. Vasomotor flushing: physiopathology and treatment]. AB - Considered for a long time as an unavoidable phenomenon secondary to a sudden reduction in hormones, the vaso-motor flushes of menopause have generated, these past few years, a renewal of interest for two reasons: 1) A better knowledge of the etiological mechanisms and experimental and therapeutic observations lead to believe at the present time that their origin is at a central level (hypothalamus) with upsetting of the balance of the cerebral neuro-transmitters; this upsetting seems to be the common mechanism of occurrence of the sudden flushes and the hormonal disorders observed during this phenomenon. 2) The possibility to use (beside the classical hormonal means) non hormonal products, especially Veralipride, which acts directly at the level of the cerebral neuro transmitters. PMID- 2876488 TI - A new diagnostic immunoassay for proximal tubule injury. AB - Adenosine deaminase binding protein (AdAbp), a glycoprotein found in the epithelial cells of the brush border of the proximal tubule, is shed into urine following kidney damage. A sandwich enzyme immunoassay is described that uses two monoclonal antibodies, URO-4 (S27) and URO-4a (S23), which react with different epitopes on AdAbp (2, 24). Release of AdAbp into the urine appears to reflect the severity of the insult to the nephron and its measurement may assist in distinguishing between tubular disease and glomerular disease and may be useful in indicating renal toxicity. PMID- 2876489 TI - The effect of gentamicin on human renal proximal tubular cells. AB - Human renal proximal tubular cells were exposed to gentamicin (0, 0.1, 0.5, 1.0, 5.0, 10.0 mg/ml medium) for 3, 7, 10, and 14 days. Cells were counted and cell viability was estimated by lactate dehydrogenase release. In addition, brush border-associated (gamma-glutamyltransferase) and lysosomal (acid phosphatase, N acetyl-beta-glucosaminidase, and sphingomyelinase) enzyme activities were measured (0.01, 1.0, 3.3 mg/ml gentamicin for 3, 7, 10 and 14 days). The number of cells did not change significantly after gentamicin treatment. Cell viability, however, significantly decreased after 3 and 7 days exposure to 5 and 10 mg/ml gentamicin. Total lactate dehydrogenase activity was significantly decreased at 7, 10, and 14 days exposure to gentamicin greater than or equal to 5.0 mg/ml. gamma-Glutamyltransferase, acid phosphatase, and sphingomyelinase were decreased at 3, 7, and 10 days exposure to gentamicin greater than or equal to 1.0 mg/ml. Continued exposure to gentamicin less than or equal to 1.0 mg/ml appeared to have little or no effect on the activity of these enzymes at 14 days. N-Acetyl-beta glucosaminidase activity, in contrast, was elevated (120-140% control) in the gentamicin-treated (greater than or equal to 1.0 mg/ml) groups at all time periods studied. Thus, gentamicin exposure resulted in changes in some of the enzyme activities in human renal proximal tubular cell cultures, but longer exposure (14 days) to gentamicin (less than or equal to 1.0 mg/ml) resulted in a return to control levels of some activities. PMID- 2876490 TI - Somatostatin: historical aspects. AB - Somatostatin, in essence an almost universal chalone, initially described as a 14 amino-acid-long peptide that inhibits growth hormone (GH) release, has been shown to be one of a family of related peptides, ubiquitous in distribution and versatile as a paracrine factor with a potentially important role in the regulation of gut, pancreatic, and nervous system function, in addition to its well-recognized influence on the pituitary secretion of GH and thyroid stimulating hormone. With the development of new super agonists, it has become possible to manipulate the endocrine milieu, to modify gut, pancreatic, and pituitary function, and, in the case of several diseases such as acromegaly and intractable diarrhoea, to make a significant advance in therapy. PMID- 2876491 TI - Proceedings of Somatostatin '85. Chemical, physiological, and clinical advances. Anugraha, Berkshire, UK, 28-29 May 1985. PMID- 2876493 TI - The role of somatostatin and a long-acting analogue, SMS 201-995, in acute bleeding due to peptic ulceration. AB - During the past 10 years several drugs have been tested for their efficacy in controlling acute upper gastrointestinal (GI) bleeding. However, since the bleeding is self-limiting in 70-80% of cases, any drug tested in all cases of upper GI bleeding will have to perform extremely well to prove significantly better than placebo. Natural somatostatin has recently been investigated on the basis that it reduces gastric acid secretion and splanchnic blood flow. In severe cases of bleeding, an average success rate of 87% has been achieved, the highest ever reported for a drug in this indication. In unselected bleeders, however, somatostatin was no more effective than placebo. The long-acting somatostatin analogue, SMS 201-995, was investigated in the current studies and was found to be more potent than natural somatostatin in reducing gastric acid secretion and in reducing intestinal mucosal blood flow for a substantially longer period. A pilot study of SMS 201-995 in the treatment of severe acute upper GI bleeding resulted in cessation of bleeding, with no rebleeding during or within 24 h after the trial in 8 of 10 patients. No side effects were reported. The planning of a large controlled trial is described. PMID- 2876492 TI - The influence of a long-acting somatostatin analogue on splanchnic haemodynamics and metabolism in healthy subjects and patients with liver cirrhosis. AB - The influence of a long-acting somatostatin octapeptide analogue (SMS 201-995) on splanchnic circulation and metabolism has been studied in healthy subjects and in patients with liver cirrhosis. In healthy subjects doses of 5, 10, 50, or 100 micrograms SMS and in the cirrhotic patients 25 micrograms SMS were infused intravenously during 1 h. Measurements were obtained before, during, and for 1 h after SMS infusion. SMS infusion in healthy subjects resulted in a 25-35% reduction in hepatic blood flow. This effect was largely independent of the dose used. Splanchnic oxygen uptake was unchanged before and during SMS infusion. Insulin and glucagon levels fell markedly in response to SMS administration, and the blood concentration and splanchnic output of glucose decreased transiently. Patients with liver cirrhosis responded to SMS infusion similarly to the healthy subjects. Hepatic blood flow decreased by 25-35% and remained suppressed for at least 1 h after infusion. Wedge hepatic venous pressure was 18 +/- 2 mm Hg in the basal state and decreased progressively during and after SMS infusion (60 min after infusion, 15 +/- 2 mm Hg; P less than 0.01). The marked hyperinsulinaemia and hyperglucagonaemia seen in the basal state decreased significantly during SMS administration. As in the case of the controls, blood concentration and splanchnic output of glucose fell transiently during and after SMS infusion. It is concluded that SMS exerts a marked and prolonged suppressive effect on hepatic blood flow in both healthy subjects and patients with liver cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876494 TI - Somatostatin localization in tissues. AB - The development of specific antibodies to somatostatin has enabled investigations on the distribution (radioimmunoassay) and precise tissue localization (immunocytochemistry) of somatostatin-immunoreactive (IR) material. Somatostatin immunoreactivity is broadly distributed both in the central nervous system and in many peripheral organs, including the gastrointestinal tract, pancreas, genitourinary system, heart, eye, thyroid, thymus, and skin. Somatostatin-IR cells display characteristic morphological features, including cytoplasmic elongations, which lend support to the postulated local or paracrine role for somatostatin. The intracytoplasmic electron-dense secretory granules in somatostatin-IR endocrine cells are characterized by their round shape, flocculent matrix, and closely apposed limiting membrane. Somatostatin-IR nerves are abundant in the gut and contain large, dense, P-type neurosecretory granules, which are distinct from those storing other peptidergic neurotransmitters. Somatostatin immunoreactivity is found frequently in neuroendocrine tumours, but the existence of the 'somatostatinoma syndrome' has recently been questioned. PMID- 2876495 TI - Neuroendocrine tumours of the gut: long-term therapy with the somatostatin analogue SMS 201-995. AB - Nine patients with metastatic neuroendocrine tumours of the gut were treated for over 100 days with the long-acting octapeptide of somatostatin, SMS 201-995. Two patients had unusually aggressive tumours (neuroendocrine tumours are typically slow-growing) with only modest elevation of tumour secretory products. SMS 201 995 was given in an attempt to slow tumour growth, but tumour size continued to increase. Three patients had glucagonomas and uncontrolled skin rashes, and four patients had VIPomas, which caused uncontrolled watery diarrhoea. SMS 201-995 was given principally to reduce hypersecretion of hormones from their tumours and to relieve symptoms. All the patients experienced rapid relief of their symptoms when SMS 201-995 treatment was introduced, and symptomatic control was maintained throughout treatment except in one patient, who required a supplementary procedure (pancreatic primary tumour embolization). Circulating peptide levels were initially suppressed, but continued suppression did not occur in every case despite good clinical control. It seems likely that SMS 201-995 has beneficial effects on target organs as well as suppressing the release of peptides from tumour tissue. The tumours did not grow during treatment. The analogue was well tolerated, most adverse effects being minor. Somatostatin inhibited insulin release, but in only one patient was there a slight deterioration of glucose tolerance. SMS 201-995 is therefore a useful therapeutic tool in the long-term management of patients with symptoms due to uncontrolled hormone secretion from neuroendocrine tumours. PMID- 2876496 TI - The response of a non-functional VIP- and somatostatin-containing tumour to tolbutamide in vitro. AB - A patient with a tumour containing clinically non-expressive somatostatin (SRIF) and vasoactive intestinal peptide (VIP) was studied in vivo with basal and tolbutamide-provoked SRIF and VIP measurements and failed to respond to tolbutamide infusion. An acute cell dispersion model was used to study this tumour after resection. Incubation of tumour cells in tolbutamide (2 mg/ml) resulted in increases in intracellular SRIF but not in the levels of SRIF released into the incubating medium. In contrast, incubation of tumour cells with tolbutamide decreased supernatant (extracellular) and total (intracellular) VIP by 50%, suggesting a local peptide-peptide modulation of VIP release by high intracellular levels of SRIF or, alternatively, suppression of VIP synthesis and/or release by tolbutamide. Failure of 'nonfunctional' tumours to produce symptoms or abnormal plasma peptide levels may be due to defects in peptide release or complex paracrine peptide-peptide interactions. PMID- 2876497 TI - Somatostatin octapeptide (SMS 201-995) in the medical treatment of acromegaly. AB - Parenteral somatostatin has been used to suppress growth hormone secretion in acromegalic patients, but long-term treatment is hampered by its short half-life of a few minutes in the circulation. An octapeptide analogue of somatostatin (SMS 201-995) has recently been developed that has greater potency and selectivity in suppressing growth hormone than the native hormone. In this study somatostatin and somatostatin octapeptide infusions were compared in 13 patients with active acromegaly. The octapeptide had a longer duration of action in the suppression of growth hormone than native somatostatin. A twice daily dose of 100 micrograms significantly suppressed growth hormone during the day. Prolactin was not suppressed, even in hyperprolactinaemic patients, and suppression of insulin was of short duration. Two patients had diarrhoea, but this disappeared when treatment with the octapeptide was stopped. Somatostatin is known to suppress pancreatic exocrine function, and it is therefore important to look for evidence of malabsorption during long-term treatment with the octapeptide. Somatostatin octapeptide is therefore useful in the treatment of acromegaly, but evidence of malabsorption should be watched for; nonparenteral routes of administration need to be assessed. PMID- 2876498 TI - Acute and long-term effects of SMS 201-995 in acromegaly. AB - The subcutaneous administration of 50 micrograms SMS 201-995 at 0815 h in 18 acromegalic patients reduced plasma growth hormone (GH) levels from 2 to 6 h after injection from 36 +/- 2 to 7 +/- 1 microgram/l (-80 +/- 5%). Circulating GH concentrations had normalized to less than 5 micrograms/l during this period in 11 of 18 patients. Postprandial blood glucose levels after breakfast were significantly (p less than 0.01) higher after SMS administration but significantly lower (p less than 0.01) after supper. Chronic treatment of five acromegalic patients with 200-300 micrograms SMS 201-995 daily for 8-24 weeks resulted in a rapid clinical improvement in all patients and complete disappearance of the complaints in four of five patients. This was accompanied by tumour shrinkage as estimated by computerized tomography scanning in three of four patients. In parallel, mean plasma GH levels and serum somatomedin-C and phosphorus levels fell to or within the normal values. SMS 201-995 represents a new tool in the medical management of acromegaly and may become the treatment of choice, especially in patients who do not benefit sufficiently from surgery and/or radiotherapy. PMID- 2876499 TI - Therapy of acromegaly with SMS 201-995: long-term studies. AB - Fourteen acromegalic patients, half of whom had been unsuccessfully treated with surgery, radiotherapy, or bromocriptine, were given the somatostatin analogue SMS 201-995 parenterally as the sole therapeutic regimen after a single administration had demonstrated suppression of serum growth hormone (GH). An impressive and sustained clinical improvement was documented in all patients, including those in whom bromocriptine had failed; most marked was the decrease in soft tissue swelling and headache and an improved performance status. GH levels decreased each time SMS 201-995 was injected but returned to basal levels within 8 h in most of the patients. With chronic therapy, 24-h mean levels were significantly suppressed, and the GH stimulability of thyrotrophin-releasing hormone and growth-hormone-releasing hormone (pl-44) was markedly reduced. Discontinuation of SMS 201-995 therapy was associated with a return of symptoms and abnormal GH dynamics. The efficacy and safety of chronically administered SMS 201-995 in active acromegaly opens new horizons for its treatment. PMID- 2876500 TI - Rationale for inhibition of growth hormone secretion in the management of the diabetic patient. AB - Patients with diabetes mellitus, especially the insulin-dependent variety, have increased circulating levels of growth hormone. On the basis of currently available information, the potential advantages of inhibition of growth hormone secretion as an adjunct in the treatment of diabetes mellitus include improved metabolic control (less hyperglycaemia, greater stability), resulting from diminution of the insulin-antagonistic actions of this hormone, and reduced micro and possibly macro-angiopathy, resulting not only from improved metabolic control but also from decreased direct effects of growth hormone on blood vessels. PMID- 2876501 TI - Effects of somatostatin and SMS 201-995 on carbohydrate metabolism in normal man. AB - Growth hormone (GH) is important in diabetes in view of its anti-insulin actions and its relation to the long-term complications of the disease. The suppression of GH secretion in diabetics has theoretical and possible therapeutic interest. Native somatostatin has multiple actions, including inhibition of the secretion of insulin, glucagon, thyroid-stimulating hormone (TSH), and various gut hormones. It also has inhibitory effects on gastrointestinal motility, exocrine secretion, nutrient absorption, and splanchnic blood flow. Its therapeutic use is limited by a duration of effect of several minutes only. SMS 201-995 holds more potential than native somatostatin in view of its longer duration of action. Preliminary data suggest that 50 micrograms SMS 201-995 subcutaneously at night inhibits the nocturnal rise in GH secretion in normal man, but no effect on 24-h GH secretion is observed when SMS 201-995 is injected twice daily before meals. SMS 201-995 inhibits secretion of insulin, glucagon, and TSH in addition to growth hormone and induces carbohydrate intolerance when administered before food in normal subjects. Gastrointestinal side effects suggest additional effects on nutrient disposal, which are important when it is administered before food. Further studies are required to elucidate these effects of SMS 201-995 on endocrine and gastro-intestinal function in normal and diabetic man. PMID- 2876502 TI - Somatostatin analogue SMS 201-995 in type I diabetes mellitus. Initial experience after repeated administration. AB - We have recently obtained encouraging short-term results after a single subcutaneous injection of the long-acting somatostatin analogue SMS 201-995 in acromegalic patients. Increased growth hormone (GH) levels may be involved in the pathogenesis of proliferative retinopathy in type I diabetes mellitus. In this study we thus investigated the effect of 3 X 50 micrograms SMS 201-995 daily on the metabolic control and hormone secretion of eight type I diabetics over a 3 day period. GH levels decreased by 32% (p less than 0.05) and somatomedin C levels by 31% (p less than 0.01) on the 3rd day of treatment compared with a control day. The insulin requirements during conventional subcutaneous insulin therapy were reduced by 28% (p less than 0.01) in seven patients without deterioration of metabolic control (mean blood glucose levels, 153.8) versus 154.7 mg/dl). Triiodothyronine, thyroxine, glucagon, prolactin, luteinizing hormone and follicle-stimulating hormone showed no significant changes. We conclude that SMS 201-995 could be an excellent tool for further clinical investigation and therapy of diabetic vascular complications. PMID- 2876503 TI - Biosynthesis and processing of the somatostatin family of peptide hormones. AB - Understanding of the biosynthesis of the somatostatin family of peptide hormones has greatly increased in recent years. Isolation and sequencing of the rat somatostatin gene indicates that it contains a single intron located between the codons for Gn(-57) and Glu(-56) of pre-prosomatostatin. The gene contains three repetitive sequences, one at the 5' end of the gene and two of them 3' to the coding portion. Two of the sequences consist of alternating purine-pyrimidine bases and have been shown to adopt Z-DNA structures in vitro. The cDNA for rat somatostatin codes for a 116-residue peptide structurally similar to the anglerfish and catfish precursors to the 14-residue somatostatin (SST-14). In addition to SST-14, the catfish and the anglerfish both contain an additional pancreatic somatostatin, each derived from a different gene. The catfish contains a 22-residue somatostatin, which is O-glycosylated at Thr-5. The second somatostatin gene from anglerfish encodes a prosomatostatin that is processed to a 28-residue peptide. The mature peptide contains a hydroxylated lysine at position 23. PMID- 2876504 TI - Physiological and pathophysiological aspects of somatostatin. AB - Somatostatin is found in the D-cells of organs that are exclusively responsible for the digestion, absorption, and metabolism of ingested nutrients. D-cells apparently release their secretory products both into the interstitial space (paracrine action) and into the circulation (endocrine action). Ingestion of all three basic nutrients--fat, carbohydrate, and particularly protein--elicits a significant increase in peripheral vein plasma somatostatin levels in dogs and humans. Acidification of a meal stimulates somatostatin release in dogs. Vagal, cholinergic, and adrenergic mechanisms exert a species-dependent effect on somatostatin release. Gut hormones also participate in the regulation of postprandial somatostatin release, and endogenous opioids have an effect that depends on the composition of the meal. Stimulation of postprandial somatostatin release by H2-receptor agonists and prostaglandins has been reported. Insulin inhibits and glucagon stimulates somatostatin release. Elevated levels of circulating glucose reduce the somatostatin response, an effect that cannot be entirely explained by the parallel augmentation of insulin secretion. Circulating nutrients also modify the effect of gut hormones on D-cell function. The physiological action of somatostatin is an inhibitory effect on virtually all gastrointestinal and pancreatic exocrine and endocrine functions. Secretory and/or motor activities are attenuated, thereby preventing an exaggerated and overshooting response. Alterations of tissue somatostatin content and plasma somatostatin levels have been observed in obesity and suggest that somatostatin deficiency may be a pathogenic factor. The observed changes of somatostatin may be secondary to alterations of other functions; nevertheless, hyposomatostatinaemia might facilitate nutrient assimilation. PMID- 2876505 TI - Somatostatin receptors. AB - More insight into the biochemical structure and operation of the somatostatin receptor(s) has been gained in recent years from several approaches. The minimal active structure of the receptor(s) has been identified, and active minisomatostatins have been synthesized. High-affinity binding sites (KDS ranging from 0.1 to 1 nM) have been demonstrated in brain and peripheral organs. In pancreas, stomach, and intestine additional low-affinity sites (or states) have been also suggested Furthermore, cytosolic receptors might be present. Binding affinities of synthetic minisomatostatins, somatostatin-14 and somatostatin-28, show different tissue specificities, suggesting the existence of different receptor subtypes. Two possible interactions of somatostatin with stimulus secretion coupling in secretory cells have been suggested: a direct activation of the GTP-dependent inhibitory subunit of adenylate cyclase and a distal activation of cytosolic phosphoprotein phosphatases. PMID- 2876506 TI - Physiological role of somatostatin in the digestive tract: gastric acid secretion, intestinal absorption, and motility. AB - Somatostatin is found in both endocrine cells and nerve fibres of the gastrointestinal tract and has several inhibitory effects on the digestive tract. Somatostatin is a potent inhibitor of gastrin release; its secretion is regulated predominantly by the cholinergic pathway, which inhibits somatostatin and thus stimulates gastrin release. Gastric acid secretion is inhibited by both the paracrine and circulating peptide (hormonal) effects of somatostatin. Somatostatin secretion is a direct effect of acid on the somatostatin cell, since it is unaffected by the axonal blocker tetrodotoxin. Somatostatin antiserum eliminates the inhibitory effect of somatostatin and thus augments acid secretion. It therefore appears that somatostatin plays a physiological role in regulating gastric acid secretion, and it is possible that a lack of the inhibitory function of somatostatin is an aetiological factor in peptic ulcer disease. Postprandially, a rise in serum somatostatin concentration occurs which is twice as high with protein and fat as it is with carbohydrates. Several studies have shown that somatostatin inhibits nutrient absorption, indicating that somatostatin might be a physiological regulator in the homeostasis of ingested nutrients by modulating the intestinal absorption rate. Experiments have also demonstrated that somatostatin infusion inhibits intestinal motility; the interval between migrating myoelectric complexes is increased, and transit time is increased. PMID- 2876508 TI - Pharmacokinetics of SMS 201-995 in healthy subjects. AB - The pharmacokinetics of a new somatostatin derivative, SMS 201-995, was investigated in a group of eight healthy subjects. SMS 201-995 was given intravenously in doses of 25 micrograms, 50 micrograms, 100 micrograms, and 200 micrograms and also subcutaneously in doses of 50 micrograms, 100 micrograms, 200 micrograms, and 400 micrograms in accordance with a randomized Latin-square design. Blood samples were taken up to 8 h. The tolerability of SMS 201-995 was very good. Routine blood chemistry variables remained normal. After intravenous administration of SMS 201-995 initial half-lives ranging from 9 +/- 2 min to 14 +/- 4 min and second half-lives of from 72 +/- 22 min to 98 +/- 37 min were calculated for the different doses. SMS 201-995 was rapidly absorbed after subcutaneous injection with a half-life ranging from 5.3 +/- 2.2 min to 11.7 +/- 7.6 min. The disposition half-life was from 88 +/- 20 min to 102 +/- 16 min for the different doses. Cp(tmax) and AUC (0 - infinity) increased dose-dependently after both routes of administration, pointing to linear pharmacokinetics for SMS 201-995. On the basis of its good tolerability, slow plasma clearance, and long action, SMS 201-995 represents a valuable tool for further clinical studies. PMID- 2876507 TI - Chemistry and pharmacology of SMS 201-995, a long-acting octapeptide analogue of somatostatin. AB - Starting from a hypothetical conformation of natural somatostatin and a knowledge of the minimal fragment needed for biological activity, a process of rational design and lead optimization has led to the potent, selective, and long-acting analogue SMS 201-995, (formula: see text) which selectively inhibits growth hormone secretion in several animal species for up to 6 h after subcutaneous application. In the rat, SMS inhibits GH, insulin, and glucagon 70, 3, and 23 times more potently than SRIF, resulting in GH/insulin and GH/glucagon selectivities of 20 and 3, respectively. The compound has been shown to inhibit growth of transplantable insulinomas in hamsters and to label selectively a subset of somatostatin receptors in the rat cortex. A radioactively labelled analogue has been used to visualize somatostatin receptors in a GRF-secreting human tumour. The stability and duration of action of SMS 201-995 after subcutaneous injection enable for the first time extended investigations of the clinical utility of somatostatin in various diseases. PMID- 2876509 TI - Postprandial effects of SMS 201-995 on gut hormones and glucose tolerance. AB - SMS 201-995 (5-100 micrograms) injected subcutaneously in normal and type-2 diabetic subjects 30 min before a test meal caused dose-related suppression of plasma concentrations of insulin, glucagon, and several regulatory gut peptide hormones (gastrin, gastric inhibitory peptide, pancreatic polypeptide, secretin, neurotensin, and motilin). Effective hormone suppression was achieved even at the lowest dose of 5 micrograms. In the normal subjects SMS caused postprandial hyperglycaemia, but there was no overall deterioration in glucose tolerance in the type-2 diabetic patients. This suggests that counterregulatory hormones play an important part in the metabolic disturbance of type-2 diabetes. PMID- 2876510 TI - The effect of SMS 201-995, a long-acting somatostatin analogue, on anterior pituitary function in healthy male volunteers. AB - The endocrine effect of SMS 201-995, an octapeptide analogue of somatostatin, was assessed during a combined anterior pituitary function test. There was no effect on the extent of hypoglycaemia after intravenous insulin infusion or on the subsequent rate of recovery of plasma glucose. SMS 201-995 administration, however, resulted in a profound and selective suppression of the GH response to hypoglycaemia without affecting the ACTH or cortisol responses. There was also a marked reduction of TSH release in response to intravenous TRH; the prolactin response was unimpaired. The LH response to LHRH was blunted and the FSH response unaffected. SMS 201-995 does not significantly impair the counterregulatory mechanisms in response to hypoglycaemia, and, in particular, the hypothalamic pituitary-adrenal axis remains intact. PMID- 2876511 TI - Human pharmacological effects of SMS 201-995 on gastric secretion. AB - The inhibition of pentagastrin-stimulated-(3 micrograms kg-1 h-1) gastric acid secretion by various doses of intravenous and subcutaneous SMS 201-995, a somatostatin analogue, was investigated in healthy volunteers by means of gastric aspiration, using phenol red as a volume marker. The intravenous doses were compared with the standard dose of somatostatin-14, 3.5 micrograms kg-1 h-1. Similarly, SMS 201-995-induced inhibition of gastric acid secretion was compared with that of exocrine pancreatic secretion assessed by gastroduodenal aspiration. The results can be summarized as follows: SMS 201-995 is a potent inhibitor of gastric acid secretion, exerting near maximal inhibition at a dose of greater than or equal to 0.56 micrograms kg-1 h-1. Near maximal inhibition equals that achieved with SST-14 (3.5 micrograms kg-1 h-1). Pancreatic enzyme secretion appears to be strongly inhibited by lower doses of SMS 201-995 than gastric secretion. Single subcutaneous injections of SMS 201-995 produce an inhibition of gastric acid secretion lasting for many hours. Near maximal inhibition was obtained with a dose of 100 micrograms. PMID- 2876512 TI - Non-antisecretory activities of H2 antagonists. AB - Besides the main effect of the H2 antagonists--that is, the inhibition of gastric acid secretion--these drugs possess several other pharmacological activities, which in most cases may be evident only for doses higher than those required to produce the H2 blockade. The non-secretory activities of the H2 antagonists may be classified into true side effects--that is, those independent of the primary action, which may or may not depend on the primary action. They concern the central and autonomic nervous systems, cardiovascular and endocrine systems, digestive system (gut, liver, pancreas), immune system, and so forth. It is obvious that when the actions of the different H2 blockers are completely at variance with regard to the same factor (cimetidine increase the TSH response to TRH, whereas ranitidine decreases it; ranitidine stimulates gastrointestinal motility, whereas oxmetidine inhibits it; ranitidine increases the exocrine pancreatic response to cholecystokinin, whereas oxmetidine decreases it; metiamide and cimetidine increase the activity of histamine methyltransferase, whereas burimamide decreases it), this is a clear demonstration that we are dealing with non-specific effects rather than with H2-receptor blockade. All these effects may be of interest because sometimes they may be useful in potentiating the primary action, and sometimes they may represent adverse reactions. In any case, they characterize pharmacologically the individual molecules of the family. PMID- 2876513 TI - The natural history of peptic ulcer disease: the influence of H2-antagonist treatment. AB - Little is known about the natural history of peptic ulcer disease. Its active phase tends to last about 15 years with a high frequency of complications (in 20 25% of cases) and recurrences after initial healing, although subsequently these problems are reduced. Until the advent of the H2 blockers, therapy (whether medical or surgical) failed to alter the course of the disease. Peptic ulcer disease, however, appears to respond positively to therapy with H2 blockers, inasmuch as these drugs at relatively low doses induce rapid healing of the ulcer in a high percentage of patients, while subsequent maintenance treatment at lower doses helps prevent recurrences and complications throughout the entire administration period. In so doing, H2 blockers improve the patients' quality of life. PMID- 2876514 TI - Episodic and residual thought pathology in chronic schizophrenics: effect of neuroleptics. AB - We sought to determine the effect of neuroleptic treatment on thought disorder in chronic schizophrenics, using the Thought Disorder Index (TDI). We were able to demonstrate that high levels of thought disorder are found in chronic schizophrenic and schizoaffective patients, while in both bipolar patients and normal controls thought pathology is minimal. Moreover, the TDI appears to be particularly well suited to the characterization of thought disorder in chronic schizophrenics. For total scores on the TDI, we were unable to demonstrate a significant reduction in thought pathology, although it was evident that thought disorder as reflected in the Conceptual Disorganization and Unusual Thought Content subscales of the Brief Psychiatric Rating Scale is significantly reduced by neuroleptics. In analyses of subscores of the TDI reflecting four levels of severity, we were able to show that more severe forms of thought pathology are normalized by neuroleptics, while less severe pathology is largely unaffected. Our results suggest that neuroleptic treatment reduces thought pathology associated with acute episodes, but that somewhat milder, though still disabling, residual thought pathology persists after clinical remission has been attained. PMID- 2876515 TI - The effect of luminal and hormonal factors on small intestinal water and electrolyte transport. AB - The effects of various biologically active peptides on net jejunal water and electrolyte fluxes were studied in dogs in vivo. Vasoactive intestinal peptide (VIP), gastric inhibitory polypeptide (GIP), glucagon, gastrin, bombesin and neurotensin all had secretagogue activity, while methionine enkephalin stimulated net absorption. Somatostatin had no effect on net basal water and electrolyte transport, but inhibited glucagon-stimulated secretion. Secretin, calcitonin, substance P and pancreatic polypeptide (PP) did not have any effect on net water and electrolyte transport in the doses used in these experiments. The precise role played by these peptides in the control of intestinal transport has still to be determined. Studies in man have confirmed that food in the proximal small bowel stimulates secretion at sites remote from the application of food, and abnormal secretion of some peptides (e.g. VIP) has been associated with diarrhoea. Somatostatin has been used successfully to reduce the volume of certain types of secretory diarrhoea. Methods used in these experiments have been applied to the study of the composition and absorption characteristics of solutions used for oral rehydration in diarrhoea and in exercise-induced dehydration. Glucose polymers have been shown to be absorbed as rapidly as glucose from the jejunum. PMID- 2876516 TI - [Barrett's ulcer: myths and realities]. AB - Barrett's ulcer, a rare disease of elderly patients, is not a precancerous condition. It has a marked tendency to bleed but not to perforate. It seems to develop in the squamous epithelium of the lower esophagus and not in the columnar epithelium of the endobrachy esophagus. PMID- 2876517 TI - [Retroviruses, human tumors and autoimmune diseases]. AB - Retroviruses are known to cause a variety of naturally occurring disorders in animals. These include various types of cancer, immune deficiencies, and degenerative and autoimmune disorders. In man, retroviruses are the causal agents of adult T-cell leukemia/lymphoma and AIDS. In addition, serologic evidence suggests the involvement of retroviruses in a variety of other human disorders including leukemias and lymphomas, and autoimmune as well as psychiatric and neurologic disorders. PMID- 2876518 TI - Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. AB - The amino acid sequences of ten proteins with intracellular half-lives less than 2 hours contain one or more regions rich in proline (P), glutamic acid (E), serine (S), and threonine (T). These PEST regions are generally, but not always, flanked by clusters containing several positively charged amino acids. Similar inspection of 35 proteins with intracellular half-lives between 20 and 220 hours revealed that only three contain a PEST region. On the basis of this information, it was anticipated that caseins, which contain several PEST sequences, would be rapidly degraded within eukaryotic cells. This expectation was confirmed by red blood cell-mediated microinjection of 125I-labeled caseins into HeLa cells where they exhibited half-lives of less than 2 hours. The rapid degradation of injected alpha- and beta-casein as well as the inverse correlation of PEST regions with intracellular stability indicate that the presence of these regions can result in the rapid intracellular degradation of the proteins containing them. PMID- 2876519 TI - AIDS and the physician. PMID- 2876520 TI - Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. AB - A novel human B-lymphotropic virus (HBLV) was isolated from the peripheral blood leukocytes of six individuals: two HTLV-III seropositive patients from the United States (one with AIDS-related lymphoma and one with dermatopathic lymphadenopathy), three HTLV-III seronegative patients from the United States (one with angioimmunoblastic lymphadenopathy, one with cutaneous T-cell lymphoma, and one with immunoblastic lymphoma), and one HTLV-III seronegative patient with acute lymphocytic leukemia from Jamaica. All six isolates were closely related by antigenic analysis, and sera from all six virus-positive patients reacted immunologically with each virus isolate. In contrast, only four sera from 220 randomly selected healthy donors and none from 12 AIDS patients without associated lymphoma were seropositive. The virus selectively infected freshly isolated human B cells and converted them into large, refractile mono- or binucleated cells with nuclear and cytoplasmic inclusion bodies. HBLV is morphologically similar to viruses of the herpesvirus family but is readily distinguishable from the known human and nonhuman primate herpesviruses by host range, in vitro biological effects, and antigenic features. PMID- 2876521 TI - [Emergency treatment of upper digestive hemorrhages in cirrhotic patients. Non surgical treatment]. PMID- 2876523 TI - [Development of medical science in Siberia and the Far East in the light of the decisions of the 27th Congress of the CPSU]. PMID- 2876522 TI - [Delusionary states in the aged]. PMID- 2876524 TI - Induction and reversion of asparagine auxotrophs in CHO-K1 and V79 cells. AB - Two asparagine-dependent clones (2002-103 and 2002-109) were obtained from CHO-K1 cells by treatment with EMS followed by a BrdU-black light selection procedure; an additional ASP- clone (2293-343) was isolated similarly from V79-56 cells. All three clones show a low rate of spontaneous reversion which is increased somewhat by exposure to EMS. Two of the variant clones (2002-103 and 2002-109) are converted in high frequency to asparagine independence by treatment with 5 azacytidine, while 2293-343 cells show no significant induction after similar exposure. All three ASP- clones were found by hybrid analyses to belong to the same complementation group. Treatment of hybrids constructed between 2002-103 or 2002-109 X 2293-343 with 5-azacytidine resulted in high-frequency induction of asparagine independence. Thus, the potential for response to 5-azacytidine in such hybrids by reversion to asparagine independence is dominant or codominant, with no suppressor effect in hybrids from the nonresponsive parent line. PMID- 2876525 TI - Hormone treatment of undescended testes. PMID- 2876526 TI - Bicycle accident injuries. AB - Bicycle accidents in 210 patients are analysed. Ages ranged from 1 to 59 years (mean 14.5 years) with a male predominance. In 52% of patients there was a head or facial injury, 6% being moderate to severe. Of the fractures 64% involved the upper limb, 32% being of the radius and ulna and 22% of the clavicle. The majority of abrasions and soft-tissue injuries involved the limbs. PMID- 2876527 TI - The significance of clostridial isolates in intra-abdominal sepsis. AB - In order to evaluate the significance of clostridial species in intra-abdominal infections, the bacteriology records of three hospitals were reviewed during a period of five years. Included in this report were 41 patients from whom clostridial species were recovered from specimens of free peritoneal fluid, abscess cavities or bile. Seven patients died for a mortality rate of 17.1 per cent. Most patients had polymicrobial infections of which clostridial organisms were one of the several anaerobes isolated. Clostridium perfringens was the single most frequently noted species, identified in 23 of the patients, but it was not associated with a different mortality rate than was observed for the other clostridial species. Clostridial bacteremia was uncommon and demonstrated in only one patient. The mean age of the patients was 56.4 years; 56.2 for males and 56.8 for females. Neither age nor sex of the patient influenced the likelihood of survival. The source of the clostridial isolates--bile, abscess cavity or free peritoneal fluid--had no effect upon the outcome. Several underlying conditions were responsible for the intraperitoneal clostridial organisms identified in this series. Only mesenteric infarction proved significantly predictive of a fatal result. Antibiotic coverage specifically directed against clostridia did not influence survival. PMID- 2876529 TI - Perioperative use of long-acting somatostatin analog (SMS 201-995) in patients with endocrine tumors of the gastroenteropancreatic axis. AB - The clinical manifestations of hormone excess caused by functioning neuroendocrine tumors of the gastroenteropancreatic (GEP) axis can be life threatening and frequently prove refractory to conventional antisecretory drugs. Administration of a long-acting somatostatin analog (SMS 201-995) proved effective in three patients with complex management problems related to GEP tumors. A patient with an insulinoma was maintained euglycemic intraoperatively with a single 100 micrograms dose of SMS given before surgery. Gastric suction in two patients with gastrinomas caused hypochlorhydric alkalosis that was preventable with preoperative SMS. Iatrogenic pancreatic fistula occurring after resection of a benign insulinoma healed within 4 days of SMS administration. This drug may be a useful adjunct in the perioperative management of patients with GEP endocrine tumors. Caution is advised regarding potential hazards related to malabsorption and gastric dysmotility. PMID- 2876528 TI - The role of clinical and biochemical criteria and endoscopic retrograde cholangiopancreatography in the urgent diagnosis of common bile duct stones in acute pancreatitis. AB - The role of clinical and biochemical criteria in predicting common bile duct (CBD) stones was analyzed in 76 patients with acute pancreatitis undergoing endoscopic retrograde cholangiopancreatography (ERCP) during the same hospital admission. Forty patients had ERCP within 72 hours; cholangiography was successful in 92%. Fifty patients had biliary pancreatitis; 25 patients had CBD stones and all were successfully removed by endoscopic sphincterotomy (ES). Twenty-six patients had nonbiliary pancreatitis. Two patients had complications from ERCP and/or ES; two patients died (no CBD stones) but ERCP was noncontributory. Significant differences were found between the biliary and nonbiliary disease groups with respect to age, and bilirubin. gamma-glutamyl transpeptidase, alkaline phosphatase, alanine transaminase, and amylase levels. The first four factors also discriminated between those patients with and without CBD stones. Logistic discriminant functions were estimated providing probabilities for the presence of CBD stones for each patient but were too cumbersome for clinical use. A simple scoring system was devised on the basis of cut-off levels: bilirubin greater than or equal to 40 mumol/L, gamma-glutamyl transpeptidase greater than or equal to 250 IU/L, alkaline phosphatase greater than or equal to 225 IU/L, and age greater than or equal to 70 years, indicating CBD stones. Bilirubin alone had a sensitivity and specificity of 80%; the specificity increased to 93% with all four factors. These results suggest that clinical and biochemical criteria and ERCP and/or ES may have important roles in the management of patients with suspected biliary pancreatitis. PMID- 2876530 TI - [Drug information. Sedatives and their application]. PMID- 2876531 TI - [Hismanal--a new nonsoporific hay fever medication]. PMID- 2876532 TI - [A case of periarteritis nodosa with isolated lesion of the lungs]. PMID- 2876533 TI - [Characteristics of kidney lesions in systemic vasculitis]. PMID- 2876534 TI - [Basal and stimulated plasma antidiuretic activity of patients with hemorrhagic fever with renal syndrome]. AB - A basal value of antidiuretic activity (ADA) of the plasma was determined in 79 HFRS patients and stimulated activity using the insulin tolerance test in 24 persons. A decrease in the plasma ADA was observed in the acute period of disease. The insulin tolerance test did not cause a statistically significant increment of the plasma ADA in the HFRS patients. PMID- 2876535 TI - Directives, methods and suggestions for anti-ulcer drug therapy. PMID- 2876537 TI - [Neurotransmission]. PMID- 2876536 TI - Forebrain ischemia in the rat. Relation between duration of ischemia, use of adjunctive ganglionic blockade and long-term recovery. AB - The relation between duration of ischemia, use of adjunctive ganglionic blockade and long-term recovery was studied in a rat model giving reversible subtotal forebrain ischemia. Ischemia was induced by bilateral carotid artery clamping and controlled hemorrhage to a mean arterial pressure of 50 mm Hg in animals artificially ventilated under 70% N2O. After variable lengths of time, the clamps were removed and the drawn blood was reinfused. In some animals, the ganglion blocker Arfonad was given (group A+) on induction of ischemia to facilitate hypotension. There was a strict dose-response relationship between duration of ischemia and mortality. Mortality was higher among animals not given Arfonad (group A-; 37% after 10 min of ischemia and 100% after 13 min) than in group A+ (about 20% after 12-13 min of ischemia, 50% after 15 min and 80% after 19 min). In group A+ more than half of the animals died later than 24 h after ischemia. All of them were hyperexcitable and 12% died during witnessed epileptic fits. Group A- animals regularly died within the first 24 h, with no indication of central nervous system involvement. Less blood had to be drawn to attain hypotension (mean arterial pressure 50 mm Hg) in group A+ (1.5 +/- 0.3 ml/100 g b.w.) than in group A- (2.5 +/- 0.2 ml/100 g b.w.). Group A+ also had less "washout" acidosis 5 min after reinfusion of the shed blood than group A- (15 min of ischemia: pH 7.24 +/- 0.07 v 6.96 +/- 0.06).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876538 TI - [Status 5 years after hormone (LH-RH) treatment of undescended testis]. PMID- 2876539 TI - [Hemorrhagic fever with renal syndrome. A survey of zoonosis]. PMID- 2876540 TI - Sensitivity of urinary enzymes as indicators of renal toxicity of the anticancer drug cis-platin. AB - Rats were intravenously injected with cis-platin in order to evaluate the sensitivity of noninvasive means of detecting renal toxicity. Doses of 8 mg/kg and 2 mg/kg were used and 7 urinary parameters (osmolality, glucose, protein, and 4 enzymes) were compared with blood urea nitrogen (BUN) and histology. Urinary enzymes usually were elevated by Day 2 posttreatment and in two cases by Day 1. Protein and glucose were elevated by Day 3 and demonstrated a greater quantitative change (10-12X control) than did urinary enzymes (2-3X controls). Enzymes, protein, and glucose all returned to control levels by Day 7 or 8, and most parameters were re-elevated again by Day 10 or 12. BUN was unaltered at the lowest dose and was increased to three times control by Day 3 after the highest dose. Cis-platin induced a mild nephrosis at the lowest dose and a proximal tubular necrosis at the highest dose. The lesion occurred at the corticomedullary junction. Biochemical changes did not correspond to the times of greatest morphological changes. Large day-day and animal-animal variation made selection of a most sensitive parameter difficult. It is concluded that one parameter is insufficient to define early renal toxicity and that a battery of several parameters would provide a better evaluation of the onset of renal toxicity. PMID- 2876541 TI - Comparative investigations on the effects of acute intraperitoneal cadmium, chromium, and mercury exposure on the kidney. AB - Urinary excretion of lactate dehydrogenase (LDH), glutathione-S-transferase (GST), leucine arylamidase (LAS), gamma-glutamyltransferase (GGT), beta galactosidase (GAL), beta-N-acetyl-D-glucosaminidase (NAG), sodium, and glucose were determined in female Sprague-Dawley rats the subsequent three days after intraperitoneal treatment with single doses of 4.5 mg CdCl2 X 1H2O/kg, 20 mg Na2CrO4/kg, and 0.75 mg HgCl2/kg body weight. Although the pathological effects were localized within the same part of the nephron (i.e., the proximal tubule), there were marked differences with regard to the extent and time course of the parameters affected. Treatment with cadmium resulted essentially in a marked decline in sodium and glucose excretion. The administration of chromate led to a slightly to moderately elevated excretion of the enzyme activities measured with the cytosolic LDH as the most increased enzyme (ca. 500% of controls on Day 3 postadministration). Median glucose excretion was unaffected whereas sodium excretion was transiently reduced. The maximum of enzyme excretion after HgCl2 was essentially the same on the first day postadministration and the amount of enzyme activity in urine up to 20 times higher compared to that after chromium. Sodium excretion was below that of controls on Days 2 and 3, whereas glucose excretion was markedly elevated (up to 8000% of controls). The results indicate that it is possible to discriminate with the use of selected urinary enzymes, substrates, and electrolytes various kinds of nephrotoxic actions not only in different but also within the same part of the nephron. PMID- 2876542 TI - [Enterotoxemia in newborn calves due to Cl. perfringens types A, C and D]. AB - The clinical symptoms and the morphologic picture of calf enterotoxemia are described. Studied were a total of thirty-two dead and slaughtered animals. Bacteriologically, the disease was shown to be caused by types A, D, and C of Clostridium perfringens. Types C and D proved pathogenic for guinea pigs, while type A did not. Isolated was a strain of Clostridium perfringens, which had high toxigenicity. It was found that calves were fairly often affected with the disease. Most severe were the infections caused by type C of Cl. perfringens, with most pronounced morphologic lesions. There were differences in the changes caused by all three types of the organism in calves, which made it possible to distinguish them as causative agents. Type A induced slight icterus and slightly manifested hemosiderosis of the liver, kidneys, and spleen; type D was responsible for severe injury and hyalin dystrophy of the kidneys; and type C caused necrotic enteritis, pronounced hemorrhagic diathesis, degenerative changes in the ganglial cells, and demyelinization of the brain. PMID- 2876543 TI - The fine structure of atypical ciliated cells in the human gastric epithelium. AB - Gastric mucosa obtained from the body and pyloric portions of the human stomach were observed by light and transmission electron microscopy. Ciliated cells were found in two of 18 subjects examined, one patient with gastric ulcer and the other one with gastric adenocarcinoma. The ciliated cells were found in epithelia at sites away from the main lesions. The tissues containing ciliated cells showed intestinal metaplasia combined with mild chronic gastritis in both cases. The epithelial layer facing the gastric lumen was composed of columnar cells with numerous uniform microvilli and goblet cells. This epithelium extended to the superficial parts of the tubules surrounded by the lamina propria. The deeper portions of the tubules were composed of mucous secretory, endocrine, and rarely ciliated cells. These ciliated cells were provided with numerous cilia the numbers of which varied considerably from cell to cell. This was in contrast to the primary cilium which is usually single. The central part of the apical cell membrane was sometimes concave in the area from where cilia tended to arise. It was also observed that numerous basal bodies as well as mucus-like granules were contained in the same cell. The axonemal pattern was different from that of ordinary cilia and showed 9 + 0 and 8 + 1 patterns. In longitudinal sections it was found that one peripheral doublet was displaced to the center of the axoneme as it left the basal body. PMID- 2876544 TI - Quantitative evaluation of leukemic mitochondria with a computer-controlled image analyzer. AB - Mitochondria from 25 patients with acute lymphoblastic leukemia (ALL) and 25 patients with acute myelogenous leukemia (AML) were compared in terms of their number, area, and shape index using a computer-controlled image analyzer. The number of mitochondria was greater in the AML than in the ALL patients. However, their size, as measured in electron micrographic profiles was similar in the two groups, in disagreement with conventional reports that mitochondria are small in granulocytes but large in lymphocytes. Two ALL patients had giant mitochondria. The mitochondria of the ALL cells were more irregular than those of the AML cells, and furthermore, within the ALL group, the degree of the irregularity was greater in those with a poor prognosis than in those in longstanding remission. The number of mitochondria was significantly greater in B-cell ALL than in null cell and T-cell ALL. PMID- 2876545 TI - Correlative histochemical studies on preneoplastic and neoplastic lesions in the kidney of rats treated with nitrosamines. AB - Renal tubular lesions induced in male rats by two different carcinogens, N nitrosomorpholine (NNM) and N-ethyl-N-hydroxyethylnitrosamine (EHEN), using a limited exposure "stop" protocol were investigated histochemically to demonstrate phenotypic cellular changes. The parameters measured included basophilia, glycogen content and the activity of the enzymes glucose-6-phosphatase (G6PASE), glycogen synthetase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphate dehydrogenase (G6PDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), succinate dehydrogenase (SDH), alkaline phosphatase (ALP), acid phosphatase (ACP) and gamma-glutamyl transpeptidase (gamma-GT). The lesions observed were predominantly of either basophilic or oncocytic types. In each case, tubular lesions (altered tubules) appeared to give rise to epithelial tumors (epitheliomas) with the same cellular phenotype. Basophilic tubules and epitheliomas proved to be strongly positive for GAPDH and G6PDH while demonstrating a reduction or loss of G6PASE, ALP, ACP, gamma-GT, and SDH compared with controls and the surrounding proximal or distal tubules. In addition, large basophilic epitheliomas demonstrated an increase in both SYN and PHO activities. In contrast, most oncocytic tubules and oncocytomas characterized by abundant densely granular cytoplasm showed a reduction in the activity of G6PDH, but were intensely positive for SDH. However, a few oncocytic lesions demonstrated a decrease in both SDH and G6PDH activity. Rarely, decreased SDH and elevated G6PDH activities were observed in altered tubules resembling oncocytic tubules. It remains to be clarified whether these tubules represent a variation of the oncocytic lesions or, perhaps, another type of tubular lesion. The results indicate that basophilic and oncocytic epithelial tumors differ in their cytochemical pattern and histogenesis. In line with earlier suggestions, the basophilic tumors apparently originate from the proximal renal tubules, while the oncocytomas develop from the distal parts of the nephron. The basophilic tumors are characterized by an increased pentose phosphate pathway and glycolysis, with a corresponding reduction in mitochondrial respiration. However, the majority of the oncocytomas show an increased activity of the mitochondrial enzyme SDH, and a marked decrease in the activity of the key enzyme of the pentose phosphate pathway. PMID- 2876546 TI - Lymphocyte emperipolesis into autologous monocytes in leukocyte cultures exposed to mitogenic lectins. AB - Lymphocyte-monocyte synergistic interaction in cooperative response to mitogens and antigens is well established. This paper describes a less known--antagonistic (effector-target)--lymphocyte-monocyte interaction that came into existence in a leukocyte culture after the commencement of cellular response to concanavalin A, phytohemagglutinin and Wistaria floribunda mitogen. An invasion of lymphocytes into monocytes and monocyte polykaryons has been found 24-48 h after exposure to mitogens. The invasion is not followed by lysosome fusion with lymphocyte-bearing vacuoles, but is associated with a sequential destruction of the vacuole wall, and eventual disintegration of some affected cells. The expression of pan-T-cell surface antigens, staining patterns for nonspecific esterase and acid phosphatase as well as ultrastructural features show that the lymphocytes entering into and those located within monocytes and polykaryons represent activated T-cells. The presence of developed Golgi complexes associated with coated and smooth vesicles, and lysosomal bodies with microvesicles, tubular arrays or dense cores suggest that these T-cells belong to subpopulations which possess cytolytic activities. The lymphocyte invasion is considered cytolytic emperipolesis directed towards some autologous cells of the mononuclear phagocyte series. Its extent depends upon the mitogen concentration, and density of cell population in the culture. It also shows individual variability. The relationship of cytolytic emperipolesis to phagocytosis, and its possible significance as a mechanism of cell-mediated elimination of undesirable cells is discussed. PMID- 2876547 TI - Evidence for a migratory capability of rat Kupffer cells to portal tracts and hepatic lymph nodes. AB - The present study concerns the migratory ability of Kupffer cells in the rat. Phagocytic cells were labeled with colloidal carbon or gold, these markers being administered intravenously either into a tail vein, which resulted in generalized reticuloendothelial uptake, or in low dose into the portal vein, which produced uptake by Kupffer cells alone. Cells containing marker were observed in the portal tracts and in hepatic lymph nodes from 1 to 3 days after injection into the portal vein. The direct movement of single marker particles to the portal tracts could be excluded. Since injection of marker into the portal vein labeled Kupffer cells exclusively, whereas blood cells, splenic and bone marrow macrophages remained unlabeled, the labeled cells in the portal tracts and hepatic lymph nodes appeared to be former Kupffer cells migrating which had migrated to these sites. PMID- 2876548 TI - Increased UDP-glucuronyltransferase and gamma-glutamyltranspeptidase in enzyme altered rat liver lesions produced by low doses of aflatoxin B1. AB - Preneoplastic liver lesions were produced in female Wistar rats by low doses of aflatoxin B1 (Model 1: administration of 37.5 micrograms/kg 12 and 24 h after partial hepatectomy; Model 2: continuous application of 3.5 micrograms/kg in tap water daily for 28 days with partial hepatectomy after 14 days. The animals then received sodium phenobarbital, 0.1% in tap water, for 180 to 400 days). In both models numerous altered hepatic foci (AHF) and hyperplastic nodules (HN) were detected enzyme histochemically by their negative ATPase and positive gamma glutamyltranspeptidase reactions. Immunohistochemically these lesions were also UDP-glucuronyltransferase positive. Increased UDP-glucuronyltransferase adds to permanent alterations of a number of drug metabolizing enzymes observed in a variety of different tumor models. These alterations are responsible for the toxin-resistant phenotype (Faber 1984b). Increased gamma-glutamyltranspeptidase was detected both enzyme histochemically and immunohistochemically; whereas gamma glutamyltranspeptidase activity was present in both AHF/HN and in periportal areas by enzyme histochemistry, the immunohistochemical method selectively stained gamma-glutamyltranspeptidase in AHF and HN. Immunohistochemically detectable UDP-glucuronyltransferase and gamma-glutamyltranspeptidase are markers of putative precancerous liver lesions which may be useful in the analysis of the prestages of liver carcinogenesis. PMID- 2876549 TI - [Compartmentalization of Ca2+ in subcellular structures of the rat liver in chemical injury of hepatocyte membranes]. AB - Compartmentalization of Ca2+ was studied in homogenates and subcellular fractions (nuclei, mitochondria, microsomes and cytosol fraction) of rat liver tissue under conditions of chemical lesion of hepatocyte membranes caused by CCl4. The studies were carried out within 2, 24, 48, 96 and 168 hrs after the CCl4 administration. The chemical lesion of hepatocyte membranes led to considerable increase in Ca2+ concentration in the subcellular fractions studied, especially in cytosol fraction, where it reached about 424% as compared with the control level. The drastic increase of calcium concentration in cytosol appears to be due to disturbance of both Ca2+ elimination through plasmatic membrane and its mitochondrial sequestration. PMID- 2876550 TI - Children with AIDS. AB - The etiologic agent for acquired immune deficiency syndrome (AIDS) has been identified as human T lymphotropic virus type III (HTLV-III). Its distinguishing characteristics and putative receptor, the T4 molecule, are discussed. The Western Blot method has been applied to assess the presence of antibody to HTLV III in patients as a measure of infection with HTLV-III. The definition of AIDS in children, based on the Centers for Disease Control surveillance criteria, is explored and expanded. Clinical and laboratory manifestations of pediatric AIDS are explained in the context of 'HTLV-III infection' through an analysis of prospective and retrospective serologic studies. Transmission of the disease is explored through parental history of infected children. Finally, the rationale for antibody replacement therapy is set forth. PMID- 2876551 TI - [Antibody formation dynamics in patients from the Far East with hemorrhagic fever with renal syndrome]. PMID- 2876552 TI - [Multiple endocrine adenomatosis manifested chiefly by hyperparathyroidism]. AB - A case with multiple endocrine neoplasia was reported, including parathyroid adenoma, of the main cells of the gland, multiple small adenomas in the tail of pancreas, (cytologically and electron-microscopically determined as A cellular) and light-cellular adenoma of adrenal. The hyperfunction of parathyroid adenoma was manifested with hypercalcemia (3.75 mmol/l), and morphologically--with the multiple calcium metastases in lungs, kidneys and heart, established at necropsy. The cause for the death was the acutely advanced ischemic disease of myocardium, on the background of chronic pyelonephritis and renal insufficiency. The timely diagnosis of such morbid states is concluded to be important for the clinical practice and could lead to the saving of the patients by operative removal of the tumour. PMID- 2876553 TI - [Beta-adrenergic blockers]. PMID- 2876555 TI - Myopathy from surreptitious ipecac ingestion. PMID- 2876554 TI - The effects of diuretics and adrenergic-blocking agents on plasma lipids. AB - ANTIHYPERTENSIVE MEDICATIONS CAUSE THE FOLLOWING CHANGES IN PLASMA LIPIDS AND LIPOPROTEINS: Thiazide and loop diuretics increase triglyceride, total cholesterol and low-density-lipoprotein (LDL) cholesterol levels with no change in high-density-lipoprotein (HDL) cholesterol. beta-Adrenergic antagonists increase triglyceride and decrease HDL cholesterol levels. A rise in very-low density-lipoprotein (VLDL) cholesterol balances the decrease in HDL cholesterol, so that there is no significant change in total cholesterol. alpha-Adrenergic antagonists decrease triglyceride, increase HDL cholesterol and may decrease VLDL and LDL cholesterol. Labetalol, with both alpha- and beta-adrenergic antagonistic activity, does not affect plasma lipids in a small number of studies. The calcium channel blockers nifedipine and verapamil also have no consistent effect on lipoprotein levels in a small number of studies. PMID- 2876556 TI - [Crohn disease in childhood]. AB - Increasing incidence of Crohn's disease particularly in childhood and adolescence has made inflammatory bowel disease one of the most important aspects of paediatric gastroenterology. The multicenter paediatric Crohn's disease study group with members from F.R.G., Switzerland, and Austria diagnosed Crohn's disease in 527 patients by means of defined diagnostic criteria. With regard to epidemiology, genetics, aetiology, descriptive pathogenesis, anamnestical and diagnostical features and therapy the authors discuss their experience and results of the multicenter study group. PMID- 2876557 TI - [Speech intelligibility as a function of prosody]. PMID- 2876558 TI - Some methodological aspects of neurosciences. PMID- 2876559 TI - [Interaction between receptors and biologically active substances in tumor cells]. PMID- 2876561 TI - [Urocaninase test for assessing the severity of the course of psoriasis]. PMID- 2876560 TI - [Regulation of gamma-glutamyltransferase activity and synthesis in animal tissues]. PMID- 2876562 TI - [Neuropharmacologic analysis of the process of developing extinctive inhibition in the lobectomized cat]. AB - Pharmacological action on cholinergic and monoaminergic brain structures in the process of food-procuring reflex extinction was studied in intact and lobectomized cats. Growing stimulation of cholinergic structures of lobectomized animals caused consecutive behavioural changes similar to those appearing during development of active reaction of intact animals to cancellation of the reflex reinforcement. In both cases influences on monoaminergic systems produced analogous effects, but suppressing influence of haloperidol injection on food procuring activity of lobectomized cats was significantly weakened. Conclusion is made that the development of active reaction of the animal to cancellation of food reinforcement is due to an increasing activation of brain cholinergic structures and consecutive activation of monoaminergic structures. Disturbance of extinction functions in lobectomized cats may be connected with disturbance of monoaminergic systems balance as a result of hyperactivity of dopaminergic structures. PMID- 2876563 TI - The mutagenic activity of agaritine--a constituent of the cultivated mushroom Agaricus bisporus--and its derivatives detected with the Salmonella/mammalian microsome assay (Ames Test). AB - Purified agaritine (N'-(gamma-L(+)-glutamyl)-p-hydroxymethylphenylhydrazine) isolated from Agaricus bisporus, p-hydrazinobenzoic acid (its presumptive precursor) and some agaritine-degradation products were tested for mutagenic activity with the Salmonella/mammalian microsome assay (Ames test). Consistent with the literature, agaritine showed a distinct direct-acting mutagenicity with the strain TA1537 (30 revertants/mumol) and with TA97. Incubation of agaritine at alkaline pH increased the mutagenic effect. Pre-incubation of agaritine with gamma-glutamyl transferase (GT) during 10 h at room temperature (pH 8.2) even enhanced the mutagenicity by a factor of 8 to 16 depending on the strain. In accordance with this finding, synthetic p-hydroxymethylphenylhydrazine (the presumptive product of the GT catalyzed degradation) showed also a distinct direct-acting mutagenicity, but the increase was only about 3- to 6- times compared with agaritine. The hypothetical ultimate mutagenic metabolite of agaritine, the p-hydroxymethylbenzenediazonium ion, a compound occurring naturally in A. bisporus, showed the highest mutagenic activity (with TA1537 approximately 300 to 1,000 revertants/mumol). PMID- 2876564 TI - Non-haemagglutinating fimbriae of enteropathogenic Escherichia coli (EPEC). AB - Two hundred and thirteen Escherichia coli strains originating in 12 countries were included in the study. Of these, 157 were classical enteropathogenic E. coli (EPEC) serotypes, 54 belonged to O138, O139 and O141 serogroups i.e. porcine edema disease strains and two strains were of serogroup O157 associated with haemorrhagic colitis. Surface hydrophobicity was determined by the salt aggregation test (SAT). Haemagglutination was assayed against erythrocytes of six animal species with strains grown under conditions known to promote expression of haemagglutinins. Sixty three EPEC strains were hydrophobic i.e. SAT value less than or equal to 0.1-1.6, and of these 15 did not haemagglutinate. Fimbriae were abundant on non-haemagglutinating strain 2178/58 (O26) when grown in nutrient broth. Fewer fimbriae per cell were present after growth on nutrient agar. Heat- and protease treatment reduces the surface hydrophobicity of EPEC strains. We propose that EPEC strains may carry a number of different surface proteins which determine binding to intestinal cells in a similar way as hydrophobic non haemagglutinating fimbriae determine binding to rabbit intestinal brush borders, cf rabbit EPEC strain RDEC 1. PMID- 2876565 TI - [Cloning of the genes of hemolytic factors of Bordetella pertussis in Escherichia coli]. AB - The gene library of B. pertussis strain No. 475 (serovar 1. 2. 3.) was obtained on plasmid pUC19 in E. coli strain JM107. The average size of the cloned fragments of chromosomal DNA was 4.9 Kb. Out of 1,700 tested recombinant clones, six caused visible hemolysis on petri dishes with agar containing 4% of sheep red blood cells after 16-hour incubation at 37 degrees C. Only two out of four isolated plasmids were similar in Pst I restriction. Consequently, the existence of several different genes responsible for the hemolytic factors of B. pertussis may be assumed. None of the cloned fragments had Hind III sites. Clones harboring hybrid plasmids possessed different modes of hemolysis, which may be indicative of gene expression in E. coli. PMID- 2876566 TI - [Immunoperoxidase study of the localization of alpha-endorphin in the brain]. AB - Location of alpha-endorphin in the rat brain was studied by means of the indirect immunoperoxidase method (peroxidase-antiperoxidase). alpha-endorphin immunoreactivity was detected in neural fibers but not in neuronal bodies. Immunoreactive fibers were located predominantly in the hypothalamus: in the preoptic area, periventricular zone, dorsal and ventrolateral portions of the gray tuber. Individual fibers containing alpha-endorphin were also discovered in the cerebral portions directly adjacent to the hypothalamus (the ventral part of the striate body, septum and thalamus). The questions related to immunocytochemical detection of peptides in the perikaryons of neurons and their processes are discussed. PMID- 2876567 TI - Catalytic and immunochemical properties of arylsulphatase A from urine, modified by potassium ferrate. AB - Arylsulphatase A (EC 3.1.6.1.) from urine was inactivated with potassium ferrate, a strong oxidizing agent. The inhibition could be prevented by competitive inhibitors, tetraborate and orthophosphate. Tetraborate which was shown to be a powerful competitive inhibitor (determined Ki = 4 X 10(-5) M) gave more efficient protection. The partially inactivated enzyme exhibited a Km value similar to that of the unmodified arylsulphatase A, and its Vmax decreased in proportion to the loss of enzymatic activity. The partially modified enzyme did not lose its ability to catalyse hydrolysis of p-nitrocatechol sulphate according to the "anomalous kinetics" exhibited towards this substrate and characteristic for arylsulphatase A. The immunochemical properties of arylsulphatase A either fully or partially inactivated were similar to those of the native enzyme. The results allow to conclude that ferrate reacts with arylsulphatase A in its active site. Thus ferrate seems to be a very sensitive probe for amino acid residues essential for catalytic activity of arylsulphatase A. PMID- 2876568 TI - [Neuroendocrinology--1986]. PMID- 2876569 TI - Negative correlation between peripheral plasma somatostatin levels and GH responses to GH-RH stimulation tests in children. AB - On forty-six fasting and resting children, aged 5-17 years, with short stature (below -2 SD) a growth hormone releasing hormone (GH-RH) stimulation test (2 micrograms/kg iv bolus, Sanofi) was performed. Twenty-two children were prepubertal, of which, 13 had a constitutional short stature (CSS), nine an idiopathic growth hormone deficiency (IGHD). Twenty-four subjects were pubertal, at the stage II or III of Tanner. Among them, six had a constitutional short stature (CSS) and 18 an idiopathic delayed puberty (IDP). Blood samples were taken for determination of plasma somatostatin-like immunoreactivity (SLI) in chilled test tubes containing EDTA + aprotinin. Plasma SLI levels were measured after extraction and concentration on C18 Sep Pack columns by radioimmunoassay using an antibody against 1-14 somatostatin. The sensitivity of this assay is around 3 pg/ml. After GH-RH stimulation the peak of GH (mean +/- SEM) was in prepubertal subjects: 25.3 +/- 9.1 micrograms/l in CSS, and 18.6 +/- 10.3 micrograms/l in IGHD. In pubertal subjects GH peaks were 17.6 +/- 8.4 micrograms/l in CSS and 15.6 +/- 3.8 micrograms/l in children with IDP. No significant differences was found between basal plasma SLI levels in the four groups of subjects, being respectively (mean +/- SEM) 11.9 +/- 1.8 pg/ml in prepubertal subjects with CSS, 9.6 +/- 2.6 pg/ml in IGHD, 7.6 +/- 1.7 pg/ml in pubertal children with CSS and 6.6 +/- 1.5 pg/ml in children with IDP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876570 TI - Reduction of pituitary size by the somatostatin analogue SMS 201-995 in a patient with an islet cell tumour secreting growth hormone releasing factor. AB - Acromegaly is rarely caused by the ectopic secretion of growth hormone releasing factor (GRF) from peripheral neuroendocrine tumours. We evaluated the ability of a recently developed somatostatin analogue (SMS 201-995, Sandoz) to reduce hormone levels and pituitary size in a young woman with acromegaly and Zollinger Ellison syndrome secondary to a metastatic pancreatic islet cell tumour secreting GRF and gastrin. Gastrin, GRF, and growth hormone (GH) levels declined dramatically following the initiation of therapy with the analogue by continuous iv infusion. Although intermittent sc therapy was not effective in suppressing hormone levels, continuous sc infusion of SMS 201-995 has provided good control of both GRF and GH levels for nine months. Moreover, treatment with SMS 201-995 was associated with a substantial reduction in pituitary enlargement and an improvement in her gastric symptoms. Continuous sc infusion of SMS 201-995 may be useful in treating enlarged pituitaries resistant to other modes of therapy. PMID- 2876571 TI - Hyperthyroidism due to non-tumoural inappropriate TSH secretion. Effect of a long acting somatostatin analogue (SMS 201-995). AB - Inappropriate hypersecretion of TSH was investigated in a 25 year old man whose hyperthyroidism had relapsed 4 years after subtotal thyroidectomy. Serum TSH levels were further increased by both TRH and metoclopramide and were partially suppressed by triiodothyronine (120 micrograms/day). The serum alpha-subunit: TSH molar ratio was less than 1.0, and computerised axial tomography showed no evidence of a pituitary tumour. These features are characteristic of inappropriate TSH secretion due to thyrotroph resistance to thyroid hormones. A long-acting somatostatin analogue (SMS 201-995), 50 micrograms injected sc twice daily for three days, suppressed TSH levels and nearly normalised thyroid hormone levels. Somatostatin analogues may be therapeutically useful in thyrotoxicosis due to non-tumoural inappropriate TSH hypersecretion. PMID- 2876573 TI - [Uricosuric action of a new beta receptor blocker-diuretic drug combination]. AB - The influence of a once daily dose of 200 mg celiprolol alone and in combination with 12.5 mg chlorthalidone on uric acid and electrolyte metabolism was investigated in 22 hypertensive patients with gout in a randomized trial. All patients were treated with allopurinol and diet. A four weeks treatment with celiprolol (11 patients) showed no influence on uric acid metabolism, electrolytes, blood glucose, cholesterol and triglycerides. Under treatment with celiprolol plus chlorthalidone (11 patients) only a small rise in serum uric acid was observed after four weeks but at the same time uric acid clearance and excretion increased significantly. There was no obvious change in serum electrolytes but an increase in sodium, potassium and chloride urine excretion. Serum uric acid, uric acid clearance and excretion decreased during a 6 months treatment period. A small decrease in cholesterol and triglycerides was observed. Blood pressure decreased in both treatment groups but there was only a small change in heart rate. PMID- 2876572 TI - The development and function of the endocrine pancreas of fetuses and infants born to normal and diabetic mothers. AB - The development of the human endocrine pancreas is described. The hormone content and islet responsiveness of foetal and neonatal pancreases of diabetic and non diabetic pregnant women are reported. PMID- 2876574 TI - Intubating conditions after vecuronium and atracurium given in divided doses (the priming technique). AB - Intubating conditions have been assessed at 60 s following administration of vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1 given either as a single dose after induction of anaesthesia with thiopentone or in divided doses; vecuronium 0.015 mg kg-1 followed 4 or 6 min later by 0.085 mg kg-1, or atracurium 0.075 mg kg-1 followed 4 or 6 min later by 0.425 mg kg-1. In the divided dose groups the smaller initial (priming) dose was given prior to induction of anaesthesia. Onset and duration of clinical relaxation were assessed using a peripheral nerve stimulator. The intubating conditions at 60 s improved significantly, with the use of relaxants in divided doses being acceptable in 80 and 70% of patients, respectively, with vecuronium and atracurium, but the conditions are not as good as those commonly found using suxamethonium. Priming at 6 min has no advantage over priming at 4 min. The onset of complete block was accelerated with priming, but the difference was not significant. The duration of clinical relaxation of vecuronium was significantly prolonged by giving it in divided doses. Unpleasant awareness of muscle weakness was observed in 15 patients, requiring early induction of anaesthesia in five of them. PMID- 2876575 TI - Hemodynamic effects of atracurium, vecuronium and pancuronium during sufentanil anesthesia for coronary artery bypass. AB - A study was undertaken to evaluate the cardiovascular effects of sufentanil, in combination with three different muscle relaxants, used as sole anesthetic with 100% O2 in 30 patients undergoing elective coronary artery vein graft surgery. Patients were randomly allocated to receive pancuronium (P), vecuronium (V) or atracurium (A) for muscle relaxation. All patients received 15 micrograms/kg sufentanil at induction followed by 5-10 micrograms/kg sufentanil prior to sternotomy. At the 95% level of significance no statistical difference was found for any of the measured and derived cardiovascular parameters between groups P, V and A, except for a decreased systolic blood pressure in the atracurium group after induction. Sufentanil in combination with pancuronium or vecuronium provided stable hemodynamic conditions throughout anesthesia. Atracurium was less satisfactory. We conclude that there is no advantage to be gained, in the presence of beta blockade, from the use of the new generation muscle relaxants as compared to pancuronium during high-dose sufentanil anesthesia for coronary artery vein grafting. PMID- 2876576 TI - Selective adrenergic beta-2-receptor blocking drug, ICI-118.551, is effective in essential tremor. AB - Eighteen patients with essential tremor were treated for 2 days with a non selective adrenergic beta-blocking drug (dl-propranolol, 80 mg X 3), a beta-2 selective blocker (ICI-118.551, 50 mg X 3) and placebo (X 3) in a randomized double blind cross-over study. Postural hand tremor was recorded with an accelerometer before administration of the drugs and at the end of each treatment period. Compared with placebo, both the beta-blocking drugs caused a statistically significant decrease in tremor intensity and they possessed approximately similar antitremor potency. Subjective benefit was reported by 12 of the 18 patients receiving ICI-118.551, 13 when on propranolol and 3 when on placebo. PMID- 2876577 TI - [Effects of alpha-methyldopa on systolic pressure and activities of tyrosine hydroxylase, dopamine-beta-hydroxylase and phenethanolamine-N-methyl-transferase in nervous system of spontaneously hypertensive rats]. PMID- 2876578 TI - [Effect of nine adrenergic drugs on experimental myocardial infarction in rats]. PMID- 2876579 TI - [Analysis of the anti-arrhythmic activity of cimetidine in anesthetized guinea pigs]. PMID- 2876580 TI - [Effects of ginseng root saponins on central transmitters and plasma corticosterone in warm-stress rats]. PMID- 2876581 TI - [Central convulsive action of l-securinine]. PMID- 2876582 TI - Effect of diazepam and medazepam on prolactin secretion. AB - Pharmacological studies of the effect of Diazepam and Medazepam on prolactin secretion were carried out on sexually mature male albino rats. The experiments were carried out using two series of experimental set-ups. In the first series an analysis was made of the effect of Diazepam in doses of 2 and 4 mg/kg body mass, and of Medazepam in doses of 1 and 10 mg/kg body mass, on the prolactin secretion on the 60th min after a single intraperitoneal injection. The second series of experiments was designed to investigate the effect of Diazepam and Medazepam in the same doses under conditions of acute immobilization of the animals for 60 min. The prolactin levels in the serum were tested using a radioimmunological method. Prolactin secretion decreases after a single intraperitoneal administration of Diazepam in both doses. Prolactin content in the serum was reduced only after a dose of 10 mg/kg body mass. Under conditions of experimental immobilization stress, prolactin secretion was stimulated in the animals from the control group, treated with standard solution used as solvent. Diazepam in both doses administered and Medazepam in a dose of 10 mg/kg inhibit the prolactin secretion stimulated by acute immobilization stress. PMID- 2876583 TI - Stearic acid desaturation in rat liver microsomes: stimulation by fatty acid binding protein. AB - A soluble protein (Mr = 12,000) showing the characteristics of fatty acid binding protein is partially purified from rat liver cytosol (15-fold on the basis of its affinity for oleic acid) using ammonium sulphate precipitation. More oleate than stearate is removed from liver microsomes incubated with similar amounts of both fatty acids and the protein, indicating that it has a higher affinity for oleic than for stearic acid. When added to microsomes, a fraction enriched in this protein stimulates stearic acid desaturation. Such an effect is abolished if the protein is pre-saturated with oleic acid. It is suggested that the stimulation of stearic acid desaturation by fatty acid binding protein may involve a selective removal of the product, oleic acid, from the microsomal membranes. PMID- 2876584 TI - The net fluid secretion caused by cyclic 3'5'-guanosine monophosphate in the rat jejunum in vivo is mediated by a local nervous reflex. AB - The tissue concentration of cyclic 3'5'-guanosine monophosphate (cGMP) has been shown to increase in the small intestine when net fluid secretion is evoked by the heat-stable enterotoxine of Escherichia coli. Lipophilic cGMP analogues are also known to elicit intestinal fluid secretion. It is therefore believed that an increase in intracellular cGMP concentration in enterocytes mediates this secretion. The present study reports that the fluid secretion, elicited by placing two different cGMP analogues, dibutyryl-cGMP and 8-Br-cGMP, in the intestinal lumen of anaesthetized rats in vivo, is significantly inhibited by atropine, hexamethonium and lidocaine. It is proposed that cGMP activates a reflex in the enteric nervous system which, in part, explains the observed fluid secretion. PMID- 2876585 TI - Vagal stimulation of duodenal HCO3(-)-secretion in anaesthetized rats. AB - The present study was designed to examine the influence of the vagal nerves on mucosa protective duodenal HCO3(-)-secretion in chloralosed rats. The HCO3(-) secretion was measured by in situ titration in a duodenal segment devoid of Brunner glands. Cervical vagotomy lowered duodenal HCO3(-)-secretion and stimulation of the cut vagal nerves (10 Hz for 15 min) increased this secretion. Both basal and vagally stimulated duodenal HCO3(-)-secretions were more pronounced in rats with ligated adrenal glands. Atropine did not influence basal duodenal HCO3(-)-secretion, whereas indomethacin and hexamethonium lowered basal secretion in vagotomized rats with ligated adrenal glands. Compared with untreated controls, vagally induced secretory responses were unchanged by atropine, 50% smaller in indomethacin treated rats and almost abolished in rats treated with hexamethonium. The study suggests that the vagal nerves exert an excitatory effect on duodenal HCO3(-)-secretion which is mainly mediated via nicotinic, non-muscarinic transmission, in part dependent on prostaglandin synthesis. Furthermore, the results indicate that the adrenal glands exert an inhibitory action on both the basal and vagally induced mucosa protective HCO3(-) secretion. PMID- 2876586 TI - Blood flow distribution, lymph flow, villus tissue osmolality and fluid and electrolyte transport after exposing the cat small intestine to sodium deoxycholate. AB - The effect of luminal perfusion of a dihydroxy bile salt (sodium deoxycholate) on net fluid transport, intestinal haemodynamics, lymph flow, electrolyte transport and villus tissue osmolality was studied in cat jejunum. Furthermore, the effects of hexamethonium and tetrodotoxin, two drugs influencing nervous activity, were investigated. Concomitant to net fluid secretion, the bile salt increased mucosal blood flow whereas capillary filtration coefficient and lymph flow remained unchanged. Net sodium and chloride transport changed from absorption to secretion. The change of sodium transport was due to both an increased flux from tissue to lumen and a reduced flux in the opposite direction. Villus tissue hyperosmolality was reduced. None of the effects on intestinal haemodynamics correlated with the change in net fluid transport. Furthermore, hexamethonium and tetrodotoxin inhibited the secretion of fluid and electrolytes without influencing the induced changes in intestinal haemodynamics. It is concluded that the bile salt induces intestinal fluid secretion by stimulating an active secretory process in the crypts via enteric nerves. A minor part of the total change in net fluid transport may be due to a reduced uptake in the villi. PMID- 2876587 TI - Microdialysis in the study of extracellular levels of amino acids in the rat brain. AB - Microdialysis has been used for in vivo studies of extracellular amino acids in rat brain. We describe a method where a probe was designed to be implanted vertically. This probe is suitable for regional stereotaxic studies of the rat brain. The dialysis probe was perfused with Ringer's solution and the perfusates were analysed for their amino acid content with a high performance liquid chromatography (HPLC) technique. An orthophthaldialdehyde derivative of the amino acids was formed before the sample was injected onto the column. In vitro studies of the dialysis probe show that the relative recovery of substances outside the membrane is dependent on perfusion speed and length of dialysing membrane but not on the concentration outside. We were also able to show that the probe was within the blood-brain barrier (BBB) when implanted into the brain since after intravenous injection of Na99mTcO4, a substance that cannot pass through the intact BBB, it was not possible to recover any isotope from the perfusate. We conclude that microdialysis is a unique method of studying regional neurochemical events within the BBB, for example, changes in putative amino acid neurotransmitters and their metabolites. PMID- 2876588 TI - Covariation of depressive symptoms, parkinsonism, and post-dexamethasone plasma cortisol levels in a bipolar patient: simultaneous response to ECT and lithium carbonate. AB - A patient presented with concurrent mood congruent delusions, parkinsonism, and elevated post-dexamethasone plasma cortisol levels. This triad could result from simultaneous development of cholinergic-monoaminergic dysfunction within critical limbic and extrapyramidal loci. The magnitude of each abnormality decreased in concert during a course of electroconvulsive therapy (ECT). Remaining abnormalities disappeared during treatment with lithium. Actions of ECT and lithium on muscarinic systems are reviewed, and a strategy for testing the hypothesis that dysfunction of cholinergic-monoaminergic mechanisms develops in parallel in different neural networks is considered. PMID- 2876589 TI - The role of glucagon, catecholamines and cortisol in counterregulation of insulin induced hypoglycemia in normal man. AB - To study the response of glucose counterregulation to insulin-induced hypoglycemia, six normals were given a 4-hour infusion of insulin (2.4 U/h) +/- somatostatin (50 micrograms/h). Supplementary glucagon (1.5 or 3.0 ng/kg/min) was given in additional experiments. In a separate study, glucagon was supplemented for 4 hours as a constant rate infusion (3.25 ng/kg/min) or at rates stepwise increasing from 1.5 to 5.0 ng/kg/min. Insulin decreased blood glucose by 1.5 mmol/l and simultaneous suppression of glucagon resulted in a more pronounced hypoglycemia enhancing the adrenaline and cortisol responses. The hyperglycemic effect of glucagon substitution (3 ng/kg/min) faded out after about 2 hours, whereafter exaggerated adrenaline and cortisol responses to hypoglycemia were seen. A comparison between the effects of steady state hyperglucagonemia and gradually appearing hyperglucagonemia on the counterregulation of hypoglycemia revealed no significant differences in glucose, adrenaline and cortisol responses to insulin. It is concluded that the glycemic effect of glucagon is transient in the hypoglycemic state. When the hepatic responsiveness to this hormone is decreased during hypoglycemia, adrenaline becomes the essential protective factor. PMID- 2876590 TI - Identification of a potent endogenous benzodiazepine binding inhibitor from bovine cerebral cortex. PMID- 2876591 TI - Purification of an endogenous benzodiazepine-like substance from the mammalian brain. AB - An anti-benzodiazepine monoclonal antibody has been used to demonstrate the existence of benzodiazepine-like molecules in the brain and for the purification of these molecules. Immunocytochemical experiments show that these molecules are neuronal and not glial and that they are ubiquitously distributed throughout the brain. Immunoblots indicate the presence of benzodiazepine-like epitopes in several brain peptides. An endogenous substance that binds to the central-type benzodiazepine receptor with agonist properties has been purified to homogeneity from the bovine brain. The purification consisted on immunoaffinity chromatography on immobilized monoclonal anti-benzodiazepine antibody followed by gel filtration on Sephadex G-25 and two reverse phase HPLCs. The purified substance has a small molecular weight and its activity is protease resistant. The endogenous substance blocks the binding of agonists, inverse agonists and antagonists to the central-type benzodiazepine receptor but it does not inhibit the binding of Ro5-4864 to the "peripheral-type" benzodiazepine receptor. The neurotransmitter gamma-amino-butyric acid increases the affinity of the benzodiazepine receptor for the purified substance. Thus this benzodiazepine-like substance is different from the endogenous benzodiazepine receptor ligands reported by others. PMID- 2876592 TI - Increased inosinate dehydrogenase activity in mycophenolic acid resistant neuroblastoma cells. PMID- 2876593 TI - Purine biosynthesis in Chinese hamster cell mutants and human fibroblasts partially deficient in adenylosuccinate lyase. PMID- 2876594 TI - Biochemical basis for deoxyadenosine and 2-chlorodeoxyadenosine toxicity to resting human lymphocytes. PMID- 2876595 TI - [Dislocations of the carpal bones. Diagnosis and therapy]. AB - Dislocations of the carpal bones are rare. Because of the difficult radiological anatomy of the carpus, the diagnosis of such injuries is often missed. The treatment of a primary diagnosed luxation is easy, and an anatomical position of the carpal bones can be achieved by closed reduction. The functional result is good. In contrast the treatment of delayed diagnosed dislocations is very problematic, and the outcome of the mainly operative therapy is unsatisfactory on the whole. The radiological findings on dislocations of the carpal bones are discussed in principle. The indication of non-operative and operative treatment is outlined. PMID- 2876596 TI - [Surgically treated carpal tunnel syndrome--clinical and electrophysiologic follow-up]. AB - The carpal tunnel syndrome is described as a compression of the N. medianus under the retinaculum flexorum with the causes for this syndrome being of the most varied nature. The aetiology is multifactorial with frequent alterations of the connective tissue being observed in the histological specimen, i.e. chronic inflammatory proliferations or fibrotic degenerations. Direct pressure measurements have shown that the pressure is markedly higher both at rest and extension or flexion as compared to normal healthy subjects. An exact diagnosis requires a measurable prolongation of the distal motorial latency. Surgery is the treatment of choice to ensure perfect recovery. For this purpose the retinaculum flexorum must be entirely split, and our experiments have shown that the splitting of the epineurium yields good results. The microsurgical interfascicular neurolysis, however, should be considered in special cases only. Complaints tend to disappear fairly quickly in the majority of cases, i.e. pain recedes by 90%, sensitivity disorders by more than 70% and muscle atrophy by 50%. The operation enables a measurable improvement of the distal motorial latency. The incidence of postoperative complications is relatively low, and if they do occur, then they are negligible and without any bearing on the final surgical result. Persistent residual complaints are very often due to other accompanying diseases such as cervical vertebral column syndrome, cervical ribs etc. PMID- 2876597 TI - [Secondary arthrosis of the wrist joint in malposition of healed and un-corrected fracture of the distal radius]. AB - Basal fracture of the radius (traumatic manus radioflex) healed in the typical false position appreciable impairs the biomechanics of the wrist. Development of secondary arthrosis is to be feared in this condition. We report on the result of a follow-up investigation of 24 patients with a false position of the distal end of the radius requiring correction. The observation period is five to 40 years. The clinical and radiological follow-up examination shows that even highly deformed wrists can retain good mobility and remain free of pain for years. The most prominent symptoms are strain pain on ulnar side of the wrist and in the region of the distal radioulnar joint. It is less the tilting of the base of the radius which is responsible for the symptoms and for the development of the arthrosis. On the contrary, the shortening of the radius plays the major role here, causing an incongruence or even luxation of the distal radioulnar joint. PMID- 2876598 TI - [Chronic fractures and pseudarthroses of the scaphoid bone of the hand. Experiences with the Ender scaphoid bone plate]. AB - We report on 37 patients with traumatic cysts and pseudoarthroses of the scaphoid, who were treated with Ender's scaphoid plate. Owing to technical errors there was no osseous healing in 4 cases (10.8%). The main advantage of this method is the brief immobilization period. PMID- 2876599 TI - [Homologous transplantation of spongiosa. Evaluation following 2 1/2 years]. AB - Sufficient stability in comminuted fractures of the lower limb, in correcting bone axis or in hip surgery can often be achieved only by adjunctive transplantation of cancellous bone. The homologous cancellous bones is cut to chips out of extracted femoral heads and frozen in a bone bank at -30 degrees C. The homologous material is available whether or not the patient himself has enough autologous spongiosa. Establishing a bone bank in a small hospital can be done with small effort and works well, as experience shows. Immunological phenomena do not cause any problems although they are responsible for the prolonged incorporation of homologous spongiosa. Out of 41 cases with such a transplantation 26 showed healing without complications, 5 weak or severe tissue reactions. 2 of 4 patients with existing infections prior to transplantation could be stabilised. 6 patients were infected after implantation of spongiosa. The condition of the soft tissue and the status of immunity in aged persons played an important role. Possibly the number of infections can be reduced by rinsing the spongiosa in antibiotic solution before implantation. PMID- 2876600 TI - [Medium term results of treatment of post-traumatic osteitis and osteomyelitis with gentamycin-PMMA minichains]. AB - In 10 cases of posttraumatic osteitis or osteomyelitis gentamicin-PMMA minichains have been used for treatment after radical local debridement. In 8 cases infection could be controlled completely by this regimen, one case needed adjuvant systemic antibiotic treatment and only one case with proved primarily gentamicin-resistant beta-haemolytic-streptococcus could be controlled after removal of PMMA-minichain by systemic antibiotic treatment. 3 to 9 months after therapy all infections were still under control. PMID- 2876601 TI - [Clinical aspects and therapy of osteomyelitis in sickle cell anemia]. AB - Sickle cell anaemia is of considerable clinical importance in parts of Africa. Special attention is drawn to skeletal involvement due to sickle cell anaemia. There is no specific therapy. Surgery is required if superinfection or a large sequestration is present. PMID- 2876602 TI - [Transverse syndrome following extension of a dislocation of the cervical spine with a Crutchfield bracket]. PMID- 2876603 TI - Binding of [3H]ICIA 5165, an H2-receptor antagonist to guinea pig gastric mucosa. AB - ICIA 5165, 2-guanidino-4-[4-(2-cyano-3-methylguanidino)butyl] thiazole, a selective histamine H2-receptor antagonist was radiolabelled with tritium to a specific activity of 50.8 Ci/mmol for use in binding studies. Radiolabelling did not impair bioactivity. Binding characteristics of [3H]ICIA 5165 to guinea pig gastric mucosa were determined. Ligand binding was rapid, reaching equilibrium within five minutes at 0 degrees C, reversible and saturable. Specific [3H]ICIA 5165 binding had an equilibrium dissociation constant of 1.29 X 10(-8) M, determined by Scatchard plot analysis, and of 1.02 X 10(-8) M, calculated from the ratio of the dissociation to association rate constants. A Hill number, nH, of 1.02 was determined for the specific binding component. Specific binding of [3H]ICIA 5165 to gastric mucosal supernatant was not inhibited by methapyrilene, diphenhydramine, mepyramine, d-chlorpheniramine or l-chlorpheniramine (all at 10( 7) M), or by atropine or propranolol (both at 10(-6) M). Specific [3H]ICIA 5165 binding was inhibited in a concentration dependent manner by non-radioactive ICIA 5165 and tiotidine, as well as by a variety of other agents, with H2 agonist or H2 antagonist properties. In competition experiments, however, difficulties encountered in accurately defining the degree of specific binding indicate some reservation should be observed in interpreting these results. PMID- 2876604 TI - [Active transport of a beta-blocker in the anterior uvea of albino rabbits]. PMID- 2876605 TI - [Study on urinary gamma-GTP activities as an indicator of cis-diamminedichloride platinum nephrotoxicity]. AB - Acute change in urinary gamma-glutamyl transpeptidase (GTP) activity following cis-diamminedichloride platinum (CDDP) administration was studied in 12 patients who had malignant tumors. The activities were measured for 11 days from the day before CDDP administration and were expressed as IU/day. In all cases, the gamma GTP activity increased with CDDP administration and decreased after completion of chemotherapy. Two peaks of gamma-GTP activity following CDDP administration were observed in many cases. In cases presenting with high gamma-GTP activity and low creatinine clearance before CDDP administration, the increase in the activity was prominent. The gamma-GTP activity before CDDP administration was significantly correlated with the gamma-GTP activity during the 10 days. This study suggests that the measurement of urinary gamma-GTP activity is important for the evaluation of CDDP nephrotoxicity, especially in cases of high gamma-GTP activity before CDDP administration. PMID- 2876606 TI - Introduction to adrenoceptor pharmacology. PMID- 2876607 TI - Pharmacology of detomidine and other alpha 2-adrenoceptor agonists in the brain. PMID- 2876608 TI - Effect of influenza virus on the interaction of cytoskeleton with cell membranes. AB - The effect of influenza virus on the organization of cytoskeleton (CS) associated with cell surface plasma membranes (PM) of chick embryo cells (CEC) was investigated. The CS isolated from virus-treated PM contained more proteins and more actin than the CS isolated from control membranes. Virus particles were found to be associated with this CS, although the purified virus alone, treated in the same manner, did not sediment at low speed in the residue insoluble in Triton X-100. Autophosphorylation of CS, especially of the polypeptides 24 K, 45 K, 65 K and 105-110 K, was increased in CS prepared from virus-treated membranes. Superprecipitation of the CS prepared from CEC was stimulated by addition of the virus. Electron microscopy of the Triton X-100 insoluble residue from virus treated PM showed more structures similar to microfilament bundles than Triton X 100 insoluble residue from control membranes. Based on these results we suggest that already in early stages the virus infection leads to a reorganization of membrane-associated CS. PMID- 2876609 TI - Analysis of influenza A virus neuraminidase using lectin test and monoclonal antibodies. AB - Influenza viruses causing epidemics in the U.S.S.R. in 1968-1982 and 1983 were analysed in the lectin test (LT) using polyclonal and monoclonal antibodies with specificity against neuraminidase (NA) of N2 subtype. Heterogeneity of the U.S.S.R. virus isolates in the reaction with monoclonal and polyclonal antibodies was demonstrated, though they were coming from the same year epidemic. The LT turned out to be an appropriate method to detect the antigenic drift in influenza virus NA. The results of LT were in a good agreement with those obtained by colorimetric estimation of the inhibition of enzyme activity and by competitive solid phase radioimmunoassay (SP RIA). In the LT only low steric inhibition of the NA with antihaemagglutinin monoclonal antibodies (MoAb) reacting in haemagglutination inhibition and virus neutralization tests was detected. PMID- 2876610 TI - Effect of the multiplicity of infection on synthesis of the tick-borne encephalitis virus-specified proteins during a single reproduction cycle. AB - The rate of the synthesis of tick-borne encephalitis (TBE) virus-specified proteins at high multiplicity of infection (MOI of 100 PFU per cell) was the highest by 8-14 hr post-infection (p.i.) as compared to the lower MOI of 4 PFU per cell (14 to 17 hr p.i.). The first virus-specific proteins appeared in cells from 2 to 5 hr p.i. PMID- 2876611 TI - Changes of natural killer cell activity in different mouse lines by acute and asymptomatic flavivirus infections. AB - Effect of certain flaviviruses on the activity of mouse natural killer (NK) cells was investigated using the classical mouse splenocyte system and YAC-1 cells for demonstration of NK cell cytotoxicity. Infection of mice with Langat and West Nile (WN) viruses was accompanied by temporary activation of NK cells. In mice infected with tick-borne encephalitis (TBE) virus the stimulation phase of NK cell cytotoxicity on days 2-4 post-infection (p.i.) was followed by suppression of their activity. As to the surface markers (sensitivity to antitheta and antiimmunoglobulin serum, respectively), the flavivirus-activated NK cells did not differ from the endogenous NK cells of intact mice. The stimulatory effect of flaviviruses on cytotoxicity of NK cells varied in different mouse lines. An increased NK cell activity at early stages of TBE virus infection was observed in mouse lines characterized by low (C57B1/6) and medium (BALB/c)--but not by high (CBA)-activity of their non-stimulated NK cells. Suppression of NK cell activity at later stages of TBE virus infection was not associated with virus multiplication in mouse splenocytes. PMID- 2876612 TI - Characterisation of orbiviruses of the Kemerovo serogroup: comparison of protein and RNA profiles. AB - Nine viruses of the Kemerovo serogroup (orbivirus genus; family, Reoviridae) isolated from seabird ticks (Ixodes uriae and Ornithodoros maritimus) from eight different geographical locations (four from Scotland, two from Morocco, one from Eire, one from England, one from the Faeroes Islands) were examined. All nine viruses produced unique RNA electropherotypes but showed a 2 : 4 : 3 : 1 grouping of the ten double-stranded RNA segments. The virus-induced proteins were labelled with 35S-methionine in a Vero cell line. Seven of the viruses isolated from Ixodes uriae produced similar profiles of nine major polypeptides. The remaining two viruses, isolated from Ornithodoros maritimus from Morocco, produced profiles in which only five major viral proteins could be readily detected, four of which had similar molecular weights to proteins apparent in the other isolates. PMID- 2876613 TI - Studies on the ecology of tick-borne encephalitis virus in the Carpathian and Pannonian types of natural foci. AB - During the years 1972-1982, the role of Ixodes ricinus ticks was studied as vectors of tick-borne encephalitis (TBE) virus in the Carpathian and Pannonian types of natural foci. The proportion of TBE virus-infected Ixodes ricinus ticks in the Carpathian elementary foci varied from 0.37 to 4.1 per cent, while in the Pannonic elementary foci it ranged from 0.07 to 6 per cent, respectively. TBE virus was isolated from organs of small rodents in both the Carpathian and Pannonian types of natural foci. A correlation was established between the percentage of infected ticks and the proportion of seropositive inhabitants. PMID- 2876614 TI - Immunoelectrophoretic characteristics of four broad bean stain virus isolates. AB - Four isolates of broad bean stain virus (BBSV; Comovirus group), representing two serotypes in immunodiffusion tests, were compared by immunoelectrophoresis. Two electrophoretic forms (slow and rapid) migrating from the cathode to the anode were found in virus preparations purified from above-ground plant parts harvested 14 or 21 days after inoculation with any of the four isolates. In virus preparations kept for a year at 4 degrees C in the presence of sodium azide both electrophoretic forms were preserved, while in preparations without a preservative only the rapidly migrating form could be detected. In virus preparations from plant roots, only the rapidly migrating form was demonstrated. PMID- 2876615 TI - Pathological lesions in mice infected with Thogoto virus, a tick-borne orthomyxovirus. AB - The RNA structure of tick-borne Thogoto virus was found very closely related to that of the Orthomyxovividae family. Pathological lesions in the lungs, liver and intestine of white mice inoculated with Thogoto virus resemble to those described for influenza virus, however, an important differential characteristic is the high hepatotropism of Thogoto virus. Thogoto virus infection in the liver of mice seems suitable for the study of virus-induced necrotic lesions. PMID- 2876616 TI - Suppression of persistent varicella-zoster virus infection in Vero cells by acyclovir. AB - Persistent infection was established in Vero cells inoculated with varicella zoster virus (VZV)-infected WI-38 cells. Treatment with 9-(2-hydroxy ethoxymethyl)guanine (acyclovir) at doses of 100, 80, 40, and 10 micrograms/ml eliminated the infectious virus, lower doses such as 0.1 and 0.01 micrograms/ml were ineffective. PMID- 2876617 TI - Vesicular stomatitis virus pseudotype with neutralization antigen of tick-borne encephalitis virus. AB - Vesicular stomatitis virus (VSV), when grown in dual infection with tick-borne encephalitis (TBE) virus, produced pseudotype VSV (TBE) with surface proteins provided by TBE virus. This phenomenon can be employed in a rapid, accurate and sensitive test for detection and assay of neutralizing antibodies specific for TBE virus. PMID- 2876618 TI - Interfering activity of epidemic, attenuated and recombinant strains of influenza A virus. AB - Interfering activity (IA) of the epidemic and attenuated influenza virus strains of different ts-phenotype was studied. IA was assessed by inhibition of vaccinia virus cytopathic effect in chick embryo chorioallantoic membrane (CAM) cells. Direct relationship was established between the temperature sensitivity (ts) index and IA of these viruses. The relationship between IA and multiplicity of infection was strain-specific. PMID- 2876619 TI - Anaerobes and septic abortion. AB - The bacterial flora of the genital tracts of twenty-two patients with septic abortion and twenty normal women (as controls) were studied to determine the significant aetiological agents. The predominant flora qualitatively and quantitatively in the twenty-two patients were anaerobes. Bacteroides bivius was isolated from all the twenty-two patients and from twelve out of twenty normal controls. The next commonest anaerobes were B. asaccharolyticus (fourteen out of twenty-two patients), B. melaninogenicus (ten out of twenty-two), B. fragilis (eleven out of twenty-two), B. disiens (eight out of twenty-two) and anaerobic cocci (six out of twenty-two); they were also isolated from nine out of twenty, twelve, zero, eight and three control subjects respectively. The commonest facultative bacteria isolated from both the patients and afebrile controls were Escherichia coli, Klebsiella aerogenes and Streptococcus faecalis. The comparative increase in number of patients colonized by the anaerobes and the increase in the bacteria, by quantitative assessment in the patient group, signify the importance of anaerobes in septic abortion. PMID- 2876620 TI - Anaerobic infections in childhood. AB - Bacteroides melaninogenicus and Bacteroides oralis are predominant anaerobes in orofacial infections and aspiration pneumonia. Fusobacterium species are common pathogens in aspiration pneumonia, brain abscesses and orofacial infections. Clostridium perfringens can cause bacteremia and wound infections. Clostridium botulinum can produce a paralytic toxin that causes a paralytic syndrome in infants. Clostridium difficile can cause diarrhea or antibiotic-associated colitis. PMID- 2876621 TI - Potentiation of nitroglycerin-induced ST segment elevation by beta-adrenergic blockade. PMID- 2876622 TI - Calcium antagonists and left ventricular function: effects of nitrendipine in congestive heart failure. AB - Calcium antagonists can affect the arterial vasculature, the venous capacitance vessels and the myocardium. The net effect of these agents on left ventricular (LV) performance depends on the interaction of effects on these 3 vascular components, and the state of LV function at the time that the drugs are administered. A calcium antagonist with profound arterial vasodilator effect might favorably influence LV performance even if it had negative inotropic properties. To demonstrate the direct effect of nitrendipine, a 1,4 dihydropyridine, on LV performance, the acute hemodynamic response to oral nitrendipine was studied in 8 patients with congestive heart failure. Administration of 10 to 20 mg of nitrendipine reduced preload, caused a decrease in both pulmonary wedge pressure and systemic vascular resistance, produced a modest decrease in blood pressure and an increase in stroke volume. In addition, plasma norepinephrine levels were significantly decreased. Plasma renin activity also tended to decrease. These data confirm that the drug can favorably alter performance of the failing left ventricle and further suggest that the vasodilator effect is not accompanied by reflex neurohumoral stimulation. PMID- 2876623 TI - Acute mastoiditis. Diagnosis and complications. AB - Thirty children with acute mastoiditis were identified over a 12-year-period and their hospital records were reviewed retrospectively. All had abnormal tympanic membranes and 26 (87%) had swelling above or posterior to the ear that deviated the pinna. Findings on mastoid roentgenograms included clouding (n = 12) and osteitis (n = 7); six were normal. From 13 patients, bacteria were recovered from normally sterile sites and included Pneumococcus (n = 5), group A streptococcus (n = 3), Haemophilus (n = 2), and anaerobes (n = 3). Complications occurred in 13 children, including subperiosteal abscess (n = 7), meningitis (n = 4), osteitis (n = 7), facial palsy (n = 1), and subdural empyema and brain abscess (n = 1). Four of the six children with neurological complications had no external signs of acute mastoiditis on physical examination. Overall, 19 (63%) of the children recovered without mastoidectomy. We conclude that children without meningitis or subperiosteal abscess may be treated initially with antimicrobial therapy plus myringotomy. The need for mastoidectomy should be reassessed in children who fail to respond in 24 to 48 hours. PMID- 2876624 TI - Intrafamilial clustering of anti-ATLA-positive persons. AB - A total of 1,333 persons in 627 families were surveyed for presence of antibody to adult T-cell leukemia-associated antigen (anti-ATLA). Each person was classified according to the anti-ATLA status (positive for sample 1, negative for sample 2) of the head of household of his or her family. In sample 1, the sex- and age-standardized prevalence of anti-ATLA was 38.5%. This was five times as high as the standardized prevalence in sample 2 (7.8%). There were significant differences in prevalence of anti-ATLA between males in samples 1 and 2 and between females in samples 1 and 2. In every age group, prevalence in sample 1 was greater than that in sample 2 except for males aged 60-69 years. In each of four subareas, families in sample 1 had higher standardized prevalence (29.6 42.5%) than families in sample 2 (6.0-9.7%). Although crude prevalence decreased with family size in sample 1 (62.1-25.4%) as well as in sample 2, indirectly standardized prevalence was almost equal within each sample, regardless of number of family members. The degree of aggregation was independent of locality and family size. These data suggest that anti-ATLA-positive persons aggregate in family units. PMID- 2876625 TI - Genetic analysis of the hypervariable region flanking the human insulin gene. AB - In order to study the mechanisms for the generation of length diversity within the 5' flanking region of the human insulin gene, we have isolated and sequenced a previously uncharacterized allele. This allele, of a size intermediate between those three already described in the literature, encompasses 1,156 base pairs (bp) and contains 81 reiterated tandem oligonucleotides of 14-15 bp each. Population analysis on 298 independently sampled individuals by Southern blotting of genomic DNA demonstrates that the polymorphic portion of the insulin 5' flanking region varies from 400 to more than 8,000 nucleotides, being encoded by from 30 to over 540 oligomeric repeats. Length variability 5' to the insulin gene is a result primarily of unequal crossing over, which generates an expansion or contraction in the number of tandem repeat units per chromosome. A similar mechanism probably accounts for nondispersed reiterated sequences at other loci in the human genome. PMID- 2876626 TI - A DNA probe for the LDL receptor gene is tightly linked to hypercholesterolemia in a pedigree with early coronary disease. AB - A large, multigenerational family with dominantly inherited hypercholesterolemia was analyzed for genetic linkage between blood levels of low-density lipoprotein (LDL) cholesterol and the locus for the LDL receptor. A genetic marker was identified by restriction fragment length polymorphism (RFLP) in a cloned segment of the LDL receptor gene. We found no exceptions to segregation of the high-LDL cholesterol phenotype with a unique allele at the LDL receptor locus in this pedigree; tight linkage was indicated by a maximum lod score of 7.52 at theta = 0. Knowledge of the LDL receptor genotype will enable investigators to study variability of phenotypic expression in response to environmental influences or to different genetic determinants. PMID- 2876627 TI - Heterogeneity in late-onset metachromatic leukodystrophy. Effect of inhibitors of cysteine proteinases. AB - The synthesis of arylsulfatase A polypeptides was followed in fibroblasts from 11 patients with late-onset forms of metachromatic leukodystrophy. In 10 cell lines, the apparent rate of synthesis was 20%-70% as measured by the amount of [35S]arylsulfatase A secreted in the presence of 10 mM NH4Cl. The specific activity of the secreted arylsulfatase A was normal. The residual activity of arylsulfatase A was below 10% except for one cell line in which it was 20%. The activity of arylsulfatase A and the degradation of sulfatides was partially restored in these fibroblast lines by treatment with irreversible (peptidyl diazomethyl ketones) or competitive (leupeptin) inhibitors of cysteine proteinases. Thus, the mutation(s) in these cell lines led to the synthesis of arylsulfatase. A polypeptides with increased susceptibility to cysteine proteinases. Multiple allelic mutations within this group of late-onset metachromatic leukodystrophy were suggested by the clinical heterogeneity, the variability of the residual activity, and in the response to inhibitors of cysteine proteinases. In fibroblasts from one patient, the apparent rate of synthesis of arylsulfatase A was less than 5%. Furthermore, inhibitors of cysteine proteinases were without effect, suggesting that the mutation in this patient is different from the others. PMID- 2876628 TI - Huntington disease-linked restriction fragment length polymorphism localized within band p16.1 of chromosome 4 by in situ hybridization. AB - A 5.5-kilobase (kb) single sequence DNA fragment (G8) reveals the DNA polymorphic locus D4S10 on Southern blot analysis. This locus is closely linked to Huntington disease and has been mapped to chromosome 4 short arm using human-mouse somatic cell hybrids, and specifically to chromosome 4 band p16 using DNA from individuals with deletions of chromosome 4 short arm who exhibit Wolf-Hirschhorn syndrome. With in situ hybridization techniques, we have confirmed the location of D4S10 on chromosome 4 and further localized it within band p16 utilizing five patients, four with overlapping chromosome 4 short-arm aberrations. The DNA segment G8 was hybridized to the mataphase chromosomes of the five patients. Two of them have different interstitial deletions of one of the chromosome 4 short arms (TA and BA), two have different chromosome 4 short-arm terminal deletions (RG and DQ), and one has a normal male karyotype. By noting the presence or absence of hybridization to the partially deleted chromosomes with known precise breakpoints, we were able to more accurately localize probe G8 to the distal half of band p16.1 of chromosome 4. PMID- 2876629 TI - The X chromosome shows less genetic variation at restriction sites than the autosomes. AB - Using a standard technique, 122 single-copy probes were screened for their ability to detect restriction fragment length polymorphisms (RFLPs) in the human genome. The use of a standardized RFLP screening enables the introduction of statistical methods in the analysis of differences in RFLP content between chromosomes and enzymes. RFLPs were detected from panels containing at least 17 unrelated chromosomes, digested with TaqI, MspI, BglII, HindIII, EcoRI, and PstI. Forty autosomal probes, representing a sample of 2,710 base pairs (bp) per haploid genome, were tested, and 24 RFLPs were found. With 82 X-chromosomal probes, 17 RFLPs were found in 6,228 bp per haploid genome. The frequency of X chromosomal RFLPs is three times less than that of the autosomes; this difference is highly significant (P = less than .001). The frequency of RFLPs revealed by various restriction enzymes and the possibility that the X chromosome is a "low mutation" niche in the human genome are discussed. PMID- 2876630 TI - Allele frequency distribution of two highly polymorphic DNA sequences in three ethnic groups and its application to the determination of paternity. AB - The allele frequency distribution of two highly polymorphic DNA sequences has been determined in three ethnic groups (American blacks, Caucasoids, and Hispanics) from the New York metropolitan area. The two loci examined were D14S1 and the flanking region of HRAS-1. The former was analyzed in EcoRI-digested DNA and the latter in TaqI-digested DNA. Approximately 700 DNA samples from unrelated individuals were digested with each of these enzymes and hybridized with the appropriate recombinant DNA probes. The size range of the DNA fragments detected for the D14S1 polymorphism varied from 14.3 to 32.5 kilobase pairs (kbp). The number of alleles identified under the experimental conditions used in this study was more than 40. For the HRAS-1 polymorphism, we have detected 18 different alleles varying in size from 1.85 to 4.5 kbp. Although the number of alleles observed in the different ethnic groups examined was very similar, the relative frequency of them varied significantly. The results presented here can be used as the basis for the utilization of DNA RFLP for the purpose of identity, such as paternity determinations or the analysis of forensic material. As an example, we have compared the results of paternity cases analyzed by HLA typing with those obtained with these two DNA polymorphisms. The values of paternity index and power of exclusion were similar by both procedures. PMID- 2876632 TI - Marked atypical lymphocytosis, hepatitis, and skin rash in sulfasalazine drug allergy. AB - A 38-year-old man presented with a generalized pruritic maculopapular rash, fever, myalgias, and edema of the face and neck. Laboratory examination revealed eosinophilia, atypical lymphocytosis, and abnormal liver function results. The clinical course was characterized by rapid resolution after initiation of steroid therapy and withdrawal of sulfasalazine, which had been started three weeks earlier for abdominal cramping and diarrhea. This clinical picture suggests a drug-induced hypersensitivity reaction to a drug commonly used for inflammatory bowel disease, sulfasalazine. PMID- 2876631 TI - Genetic studies on the Tharu population of Nepal: restriction endonuclease polymorphisms of mitochondrial DNA. AB - The mitochondrial DNAs (mtDNAs) of 91 Tharus from Nepal were screened for restriction fragment length polymorphisms (RFLPs) using six highly informative restriction endonucleases. One pattern (morph) was found for BamHI, two for HpaI and HincII, three for HaeII, four for AvaII, and six for MspI. Two of the AvaII and four of the MspI morphs were "new" (not previously described). Virtually all of the "old" morphs found in the Tharus were previously observed in Orientals. The Oriental HaeII morph (HaeII-5) previously observed at a frequency of 5% was present in 25% of the Tharus. Of the 13 Tharu mtDNA types (defined by the six restriction endonuclease morphs) observed, five had previously been described ("old" types), all in Orientals. Three of these were unique for Orientals. All of the remaining eight "new" Tharu mtDNAs were all closely related to Oriental mtDNAs. Two of the "old" Tharu mtDNA types included the HpaI/HincII morph 1, a morph possibly indicative of the earliest human mtDNA types. From these data we have concluded that the Tharu mtDNAs are closely related to those of other Oriental populations. Further, our data support the hypothesis that human mtDNAs radiated from Asia. PMID- 2876633 TI - Total ischemic burden: definition, mechanisms, and therapeutic implications. AB - The concept of the total ischemic burden includes all types of ischemia encompassing both silent and symptomatic ischemic episodes. This concept is currently causing a re-evaluation of current therapeutic goals for patients with coronary heart disease. Although the mechanism of cardiac pain is still unclear, we do have some information about other pathophysiologic mechanisms at work in this disorder. We think of ischemia as occurring secondary to reduced supply (primary ischemia), increased demand (secondary ischemia), or a combination of the two (mixed ischemia). Because of the lower heart rate associated with many episodes of ischemia during everyday activities, suggesting that vasoconstriction is playing a role in the patient's supply/demand imbalance, calcium antagonists appear to be particularly useful agents for the treatment of vasoconstriction in patients with angina. PMID- 2876634 TI - Alternative medical treatment for patients with angina pectoris and adverse reactions to beta blockers. Usefulness of nifedipine. AB - Although beta blockers are effective for the treatment of angina pectoris, chronic adverse effects produced by these agents--including lethargy, fatigue, and male impotence--can adversely affect patient acceptance and treatment compliance. To assess the clinical effects of switching from anti-anginal treatment with beta blocker only (phase I) to half-dose beta blocker plus the calcium blocker nifedipine (phase II) or nifedipine alone (phase III), 18 patients with chronic stable angina pectoris and side effects to beta blockers were evaluated in a 12-week, open-label trial. Three patients did not complete the study, one secondary to new unstable angina and two secondary to nifedipine side effects. Of the 15 patients completing the trial (13 men and two women; mean age, 54 +/- 5 [SEM] years), all sequentially participated in the one-month phases. Weekly angina frequency assessed from patient diaries was significantly less for treatment with nifedipine only (phase III) as compared with beta blocker (phase I) (1.7 +/- 1 versus 3.9 +/- 1 episodes per week), while phase II was not significantly different. Exercise test time was maintained throughout all phases (phase I, 457 +/- 39; phase II, 458 +/- 40; and phase III, 498 +/- 48 seconds, p not significant). All 15 patients in phase I (100 percent) had side effects to beta blockers, but these side effects were lessened in 12 patients (80 percent) in phase II and 13 patients (86 percent) in phase III, with total alleviation of symptoms in two patients (13 percent) in phase II, and eight patients (53 percent) in phase III. Thus, in patients with side effects to beta blockers, switching to nifedipine is associated with a significant reduction in beta blocker adverse symptoms and equal anti-anginal efficacy. PMID- 2876635 TI - Effect of nifedipine on left ventricular function in patients with angina pectoris. AB - Calcium channel blocking agents function as negative inotropic agents when they are administered in vitro directly to the myocardium. In patients with coronary artery disease, however, such direct effects are attenuated by a number of other factors, including decreased afterload and resultant reflex sympathetic stimulation, increased coronary blood flow with improved myocardial perfusion, and protection of mitochondria. Nifedipine has not been observed to cause significant left ventricular depression in patients with angina pectoris; this is primarily due to peripheral arteriolar vasodilatation, which reduces impedance of left ventricular ejection. In addition, the relief of myocardial ischemia by nifedipine plays a major role in improving systolic and diastolic function. The clinical response to calcium channel blockers may differ in patients with idiopathic dilated cardiomyopathy, for whom the factor of fluctuating ischemia is less important. PMID- 2876637 TI - Ocular jellyfish stings in Chesapeake Bay watermen. PMID- 2876636 TI - Assessing the total ischemic burden in the management of unstable angina. A review. AB - Unstable angina is a common ischemic syndrome that is characterized by chest pain occurring at rest often with transient ischemic electrocardiographic changes. Although most patients with unstable angina experience relief of pain with intensive medical therapy while in the coronary care unit, they subsequently have a high incidence of unfavorable cardiac events usually occurring within several months. Continuous electrocardiographic monitoring for ischemia has demonstrated a relatively high incidence of ischemic episodes both in patients with stable and unstable angina pectoris. The prognostic importance of such findings has been previously uncertain. The prognostic significance of silent myocardial ischemia in patients with unstable angina receiving intensive medical therapy has been addressed in a study of hospitalized patients in a coronary care unit. All patients were treated with nitrates, nifedipine, and propranolol. Continuous two channel electrocardiographic monitoring was performed during the first two days of medical therapy. The electrocardiographic recordings were interpreted blindly for frequency and duration of ischemic changes, and these episodes were determined to be either symptomatic or silent. The prevalence of silent ischemic episodes, their prognostic significance, their contribution to the total ischemic burden, and the effects of different medical regimens on these variables are discussed. PMID- 2876638 TI - Polyarteritis nodosa diagnosed by temporal artery biopsy. PMID- 2876639 TI - Effect of DL-penicillamine on the aorta of growing chickens. Ultrastructural and biochemical studies. AB - The effect of DL-penicillamine on the architecture of the aortic wall of growing chickens was studied, with particular attention to elastin and collagen. Penicillamine was added to the diet (0.2% and 0.4%, in the presence or not of 10 mg/kg CuSO4 and 100 mg/kg vitamin B6) from hatching, for periods from 7 days up to 2 months. The same regions of the thoracic aortas were examined and compared in all the different experimental conditions. The results showed that penicillamine induced relevant modifications in the process of elastin fibrogenesis. The alterations consisted of an increase of elastin in the extracellular space, associated with an increase in the number of elastin fibers per unit area, and a decrease of the mean profile area of the fibers. Interestingly, penicillamine induced the formation of numerous bundles of microfibrils associated or not with elastin fibers. After prolonged treatment, elastin tended to diminish and the fibers tended to fuse into polymorphic syncytia. Collagen fibrils were larger, showed more heterogeneous cross diameters, were less numerous, and were more spread out within the tissue. All the other components of the aortic wall appeared not to be altered by the chemical. Penicillamine did not modify the copper content of chick aortas, whereas it induced a 40-50% reduction of the activity of both salt and 4 M urea soluble peptidyl lysyl oxidases in the same tissue. These data may help in understanding some of the pathologic manifestations in human beings during D penicillamine treatment. PMID- 2876641 TI - In vivo inhibition of tyrosine uptake into rat retina by large neutral but not acidic amino acids. AB - The uptake of tyrosine into rat retina and brain was studied in vivo after its peripheral injection alone or in combination with other amino acids. Both retinal and brain tyrosine levels increased monotonically for at least 60 min after tyrosine administration. When tyrosine was injected along with branched-chain amino acids, but not with acidic amino acids, such increments in retinal and brain tyrosine levels were significantly attenuated. The postinjection tyrosine levels in retina and brain paralleled better the serum ratio of tyrosine to the sum of the other large neutral amino acids (which include the branched-chain amino acids) than the serum tyrosine level alone. These results suggest that tyrosine uptake into rat retina, like that into brain, is mediated by a competitive transport system shared among the large neutral amino acids. PMID- 2876642 TI - Brown adipose tissue thermogenesis, torpor, and obesity of glutamate-treated mice. AB - Mice treated with glutamate in the neonatal period are known to develop into stunted obese adults, despite hypophagia. Our objective was to find out whether brown adipose tissue (BAT) thermogenic function might be abnormal in the glutamate-obese mouse. At 10 wk of age, group-housed glutamate-obese mice exhibited nocturnal and early diurnal torpor, i.e., they thermoregulated at a lower than normal body temperature. When exposed to 4 degrees C, they died in hypothermia within 24 h. They could adapt to living at 14 degrees C for up to 1 wk but failed to adjust their food intake sufficiently to maintain their body weight. Their fat stores were, nevertheless, conserved. BAT was present in increased amounts in glutamate-obese mice. Its thermogenic activity (as assessed by the level of mitochondrial GDP binding) was normal (male mice) or reduced (female mice). A normal thermogenic responsiveness of BAT to cold occurred. The thermogenic response of BAT to a cafeteria diet was normal (male mice) or reduced (female mice). Serum corticosterone concentration was increased in both male and female glutamate-treated mice particularly in the cold. We conclude that the high metabolic efficiency and obesity of the glutamate-obese mouse are principally a consequence of its maintenance of a hypothermic torpid state for more than 50% of the time. An additional deficit in energy expenditure in female, but not male, glutamate-obese mice is associated with suppressed responsiveness of the thermogenic function of BAT to diet and may account for the greater degree of obesity in female than in male glutamate-treated mice. PMID- 2876643 TI - Mechanism of central hyperglycemic effect of cholinergic agonists in fasted rats. AB - The influence of cholinergic agonists on central nervous system (CNS) regulation of blood sugar homeostasis was studied in fasted rats. When carbachol, muscarine, bethanechol, methacholine, or neostigmine was injected into the third cerebral ventricle, it caused a dose-dependent increase in the hepatic venous plasma glucose concentration. However, in the case of 1,1-dimethylphenyl-4-piperazinium iodide (DMPP) or nicotine, the level of hepatic venous glucose did not differ from that of the saline-treated control rats. The increase in glucose level caused by neostigmine was dose-dependently suppressed by coadministration of atropine. These facts suggest that cholinergic activation of muscarinic receptors in the CNS plays a role in increasing hepatic glucose output. Injection of neostigmine (5 X 10(-8) mol), an inhibitor of cholinesterase, into the ventricle resulted in the increase of not only glucose, but also glucagon, epinephrine, and norepinephrine in the hepatic venous plasma. However, constant infusion of somatostatin through a femoral vein completely prevented the increase of glucagon after administration of neostigmine, although the increase of hepatic venous glucose and epinephrine levels were still observed. Neostigmine-induced increments in glucose did not occur in adrenalectomized rats. This suggests that the secreted epinephrine acts directly on the liver to increase hepatic glucose output. PMID- 2876640 TI - The neuropathology of AIDS. UCLA experience and review. AB - The central nervous system (CNS) has been examined at autopsy in 89 patients who died of the acquired immune deficiency syndrome (AIDS), including 14 patients who died primarily of neurologic complications of the disease. A total of 66 brains (74%) showed significant pathologic abnormalities, with opportunistic infections including cytomegalovirus (14) and cryptococcal (11) infections, progressive multifocal leukoencephalopathy (6), toxoplasmosis (6), and histoplasma microabscesses (1). Incidental Mycobacterium avium-intracellulare infection was found in 4 cases. Simultaneous CNS infection by more than one microorganism was encountered in 5 patients. Subacute (microglial nodule) encephalitis-related to cytomegalovirus infection or possibly brain infection by the causative agent of AIDS was present in 56 cases. Primary CNS lymphoma was noted in 3 patients. Secondary CNS deposits of lymphoma were found in 1 patient, and another patient had lymphomatoid granulomatosis. Vascular complications were not infrequently seen, and included infarcts secondary to vessel occlusion and disseminated intravascular coagulation in 4 patients and intracranial hemorrhage of variable severity in 13. White matter changes included vacuolar myelopathy (3 cases), central pontine myelinolysis (1 case), and foci of calcified, necrotizing leukoencephalopathy in pontocerebellar fibers of the basis pontis (2 cases). These findings highlight the variety of CNS complications in AIDS, some of which are not associated with clinical manifestations. Nevertheless, characterization of all lesions may be important in understanding the neurologic sequelae of AIDS. PMID- 2876644 TI - Carrier-mediated transport of enkephalins and N-Tyr-MIF-1 across blood-brain barrier. AB - The saturable, carrier-mediated system capable of the brain-to-blood transport of small peptides with an N-terminal tyrosine was characterized. The rate of disappearance of intraventricularly injected iodinated peptide in the presence or absence of the inhibitor being tested was determined from formulas based on the residual radioactivity in the brains of mice after decapitation. The injection of 100 nmol/mouse of unlabeled N-Tyr-MIF-1 (TMIF) increased the half-time disappearance of 125I-TMIF (ITMIF) in the central nervous system (CNS) from 14.1 to 88.7 min (P less than 0.00005). Technetium, a substance transported out of the brain by the same system that transports iodine, was used as a control; the half time disappearance of technetium pertechnetate was unaffected by unlabeled TMIF. With two related but distinct techniques, the maximum transport rate out of the CNS (Vmax) for TMIF was 0.266 nmol X g of brain per min (method 1) and 0.297 nmol X g-1 X min-1 (method 2), while the amount of unlabeled material needed to achieve 50% of Vmax (Km) was 15.2 nmol/g (method 1) and 15.1 nmol/g (method 2). The lack of effect of the tyrosinated fragments of TMIF as inhibitors indicates that TMIF is being transported in intact form. The Vmax for methionine enkephalin determined with labeled and unlabeled methionine enkephalin was 0.630 nmol X g-1 X min-1 and the Km was 24.95 nmol/g. Studies with the metabolic modulators furosemide, acetozolamide, reserpine, ouabain, and theophylline suggest that the system is sodium dependent and probably independent of ATPase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876645 TI - Inhibitory effects of beta-adrenergic agonists on gastric acid secretion in dogs. AB - We evaluated the effect of two beta-adrenergic agonists, isoproterenol (nonselective agonist) and terbutaline (selective beta 2-agonist), on gastric acid secretion stimulated by intravenous pentagastrin, bethanechol, or histamine in dogs with gastric fistulas. Intravenous infusion of isoproterenol or terbutaline inhibited pentagastrin-stimulated acid secretion to a significantly greater extent than they inhibited bethanechol- or histamine-stimulated acid secretion. For example, isoproterenol (12 micrograms X kg-1 X h-1) reduced mean pentagastrin-, bethanechol-, and histamine-stimulated acid output by 86, 63, and 14%, respectively. Percent inhibition of acid secretion with terbutaline (30 micrograms X kg-1 X h-1) averaged 60, 17, and 24% for pentagastrin, bethanechol, and histamine, respectively. Terbutaline also inhibited pentagastrin-stimulated acid secretion from vagally denervated fundic pouches in a dose-related manner. Plasma somatostatin-like immunoreactivity was significantly higher during infusion of terbutaline plus pentagastrin than during infusion of pentagastrin alone. However, an intravenous infusion of 0.3 microgram X kg-1 X h-1 somatostatin-14 had no effect on pentagastrin-stimulated acid secretion from the gastric fistula, even though this infusion increased plasma somatostatin-like immunoreactivity to the same extent as terbutaline plus pentagastrin infusion. Thus the amount of somatostatin released during terbutaline infusion was not sufficient to explain the inhibition of pentagastrin-stimulated acid secretion observed. PMID- 2876646 TI - Effect of acute experimental colitis on rabbit colonic smooth muscle. AB - The membrane potential and contractile activity of colonic circular smooth muscle from New Zealand White rabbits were studied after the production of acute experimental colitis. Colitis was induced in the distal colon by rectal infusion of formaldehyde solution, followed by an intravenous bolus of soluble immune complexes. Despite active mucosal inflammation, there are only occasional inflammatory cells in the muscularis. Electrophysiological studies on tissue from control rabbits and rabbits with colitis were performed using double sucrose gap and intracellular microelectrode techniques. The resting membrane potential was lower (-44 +/- 3 mV) in muscle from rabbits with colitis compared with control animals (-54 +/- 2 mV) (P less than 0.02). Amplitude of the electrotonic potential after a hyperpolarizing current pulse was decreased (P less than 0.05) and the time constant was shortened (P less than 0.01) in muscle from animals with colitis compared with normal animals. Amplitude (13.1 +/- 2.3 mV) and maximum rate of rise (0.24 +/- 0.06 V/s) of the spike potential, initiated by a depolarizing current pulse, were decreased in muscle from animals with colitis compared with muscle from healthy animals (P less than 0.001). Isometric tension generation after electrical and chemical depolarization of the membrane or bethanechol administration was decreased (P less than 0.001) in muscle from colitic animals. These studies suggest 1) membrane resistance and membrane potential are decreased in muscle strips from animals with colitis; and 2) there is a disturbance in the electrical and mechanical response of these tissues after stimulation. PMID- 2876647 TI - Frequency and presentation of neuroleptic malignant syndrome in a large psychiatric hospital. AB - Neuroleptic malignant syndrome, a dangerous but little-known complication of antipsychotic drugs, is often assumed to be rare. To assess the frequency of the syndrome in a large psychiatric hospital, the authors first reviewed the literature and developed operational diagnostic criteria. Using these criteria to survey nearly 500 neuroleptic-treated patients admitted during a 1-year period, they found that seven (1.4%) had experienced definite or probable neuroleptic malignant syndrome. In several cases, including one fatal case, the diagnosis of neuroleptic malignant syndrome was not immediately considered. The authors conclude that neuroleptic malignant syndrome may be more common than previously thought and may be underdiagnosed. PMID- 2876648 TI - Neuroleptic malignant syndrome: the pendulum swings. PMID- 2876649 TI - Combined alprazolam and neuroleptic drug in treating schizophrenia. PMID- 2876650 TI - The use of low-dose neuroleptics in the treatment of "schizo-obsessive" patients. PMID- 2876651 TI - Schizophrenia and gastric surgery for obesity. PMID- 2876652 TI - Retrieval variability: sources and consequences. AB - A memory model that differentiates between active traces (ongoing electrochemical neural transmission) and passive traces (chemical/structural modification of neurons) is briefly outlined. Evidence suggests that new information is initially encoded as a passive representation within a fraction of a second, leaving little opportunity for retroactive interference with storage processes. Instead, it appears that retroactive interference results from disruption of post-acquisition processing which is necessary for subsequent retrieval. Using this hybrid cognitive-physiological framework, we examine possible sources of associative performance deficits. A distinction is made between similarity interference (arising from the content similarity of the target and interfering traces) and processing interference (arising from the competition between the two traces for use of a limited capacity processor). Both types of interference can act proactively or retroactively, and the similarity-processing and proactive retroactive dimensions are viewed as orthogonal to the question of whether information is permanently lost or merely subject to a reversible retrieval failure. When reminder techniques (pretest cuing) are used, numerous instances of memory failure commonly identified as "acquisition failures" are found to be reversible without the occurrence of relevant new learning. This literature review constitutes the greater part of the paper. It is concluded that many memory failures are due at least in part to retrieval failure. Consideration of potential retrieval processes in light of the studies that are reviewed argues for the expansion of the initial active-passive trace distinction to three types of traces. In addition to active traces, these include two distinct types of passive traces, i.e., a small content-addressable reference catalog with innately defined dimensions that is used to locate more detailed passive traces, and a large capacity store of detailed passive traces that is location-addressable. The latter type of passive trace presumably is laid down almost instantaneously as events occur, i.e., in real time, whereas the reference catalog type of passive trace, which is used to address the detailed traces, is established somewhat after the sequence of events is complete. Hence, the reference catalog trace is more vulnerable and results in retrieval failure when it is disrupted.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2876653 TI - Benefits and limitations of neuroleptics--and other forms of treatment--in schizophrenia. AB - Neuroleptic drugs are of proven value in schizophrenia for both the treatment of acute psychotic states and for the prevention of relapse in patients who have recovered from psychosis. However, these drugs have a number of important limitations: they are not effective for all patients, they have a number of serious adverse effects, and they are limited in what they can do. Some of the more serious side effects, particular tardive dyskinesia, require that clinicians use these drugs only in situations when they are demonstrably effective, and at the lowest effective dose. For most schizophrenic patients, neuroleptics should be only one part of a treatment program which will also include appropriate psychosocial treatment. PMID- 2876654 TI - Can drugs be used to enhance the psychotherapeutic process? AB - Many preindustrial cultures traditionally use certain psychedelic plants to enhance a procedure that resembles psychotherapy--an idea that was also tested in Western psychiatry in the 1950s and 1960s. LSD and related drugs were used to facilitate the production of memories, fantasies and insights and to enhance the therapeutic alliance. The results were inconclusive, and research was largely abandoned after the drugs became difficult to obtain. It may now be possible to revive this research, using new drugs that do not have some of the disadvantages of the old ones. The drug now of most interest is MDMA (3,4 methylenedioxymethamphetamine) a relatively mild and short-acting substance that is said to give a heightened capacity for introspection and intimacy without the perceptual changes, emotional unpredictability, and occasional adverse reactions associated with LSD. Therapists who have used the drug claim that it can enhance the therapeutic alliance by inviting self-disclosure and promoting trust. Whether MDMA fulfills this promise or not, other drugs may eventually prove useful in psychotherapy. Research on their potential should not be curtailed because of fear that they will be subject to illicit abuse. PMID- 2876655 TI - Non-physician providers. PMID- 2876657 TI - [Concern for human health in the resolutions of the 27th Congress of the CPSU]. PMID- 2876656 TI - The detection of enteropathogens in acute diarrhea in a family cohort population in rural Egypt. AB - In 8 villages of rural northeastern Egypt, a 2-year study of the etiologic agents associated with episodes of diarrhea was carried out. Stool specimens (3,243) from 3,513 episodes of diarrhea were processed for enteropathogens. The most commonly identified agents in the group with diarrhea were Giardia lamblia (44%), heat stable enterotoxin (ST)-producing enterotoxigenic Escherichia coli (ETEC) (15%), heat labile toxin (LT)-producing ETEC (12%), enteropathogenic E. coli (EPEC) (4%), rotavirus (3%), Shigella (2%) and Salmonella (1%). Isolation rates were increased in cases compared to controls for all agents except G. lamblia and EPEC strains. Rotavirus, Salmonella and ST-producing ETEC were more frequently isolated during cooler months and Shigella and LT-ETEC occurred more commonly in warmer months. Campylobacter, EPEC, Giardia and E. histolytica did not show a discernable seasonal pattern. Rotavirus was primarily associated with diarrhea in infants only. Forty-four percent of children experienced at least 1 bout of rotavirus diarrhea by the age of 3 years. Vomiting was reported in 65% of cases of rotavirus infection. Dehydration was reported in greater than 40% of those with rotavirus-, Salmonella-, Campylobacter-, LT-ETEC- and EPEC-associated illness and in those without an identifiable agent. While rotavirus was implicated in 3% of cases overall, when vomiting or vomiting plus dehydration occurred, rotavirus was identified with a rate of 10% and 12%, respectively. Dysentery was common only in Shigella cases, occurring in 24%. A decrease in occurrence of rotavirus, Campylobacter and possibly EPEC illness was seen in the infants less than 6 months of age who were breast-fed when compared to those who were not. PMID- 2876658 TI - Terbutaline slow-release tablets in children with asthma. A comparison with t.i.d. beta 2-agonist therapy. AB - The effects of 5 mg slow-release terbutaline sulphate tablets (Bricanyl Depot) given twice daily were compared with those of ordinary oral beta 2-agonist treatment given three times daily. The study was open, randomized and cross-over and was carried out over 8 weeks in 18 children with bronchial asthma. Compared with ordinary medication, the slow-release tablets obtained higher morning expiratory peak flow values and an improvement in the asthma symptoms during the night and during exercise (P less than 0.05). No differences were found in side effects in spite of a higher total daily dose during the period with terbutaline slow-release tablets. The slow-release tablets were preferred by 15 of 18 children and their families when the effects, side effects and dosage were evaluated. PMID- 2876659 TI - Accelerated differentiation in seminiferous tubules of fetal mice prenatally exposed to ethinyl estradiol. AB - Ethinyl estradiol (EE) in olive oil (0.02, 0.2, or 2.0 mg/kg) administered to pregnant mice on days 11 to 17 of pregnancy induced abnormal differentiation of gonocytes and fetal Sertoli cells in male fetuses on day 18 of gestation. Light and electron microscopic examination of the testes showed fewer darkly stained prospermatogonia and more lightly stained prospermatogonia in the experimental than in the control fetuses. Widespread degeneration and lysis of gonocytes were seen only in the experimental mice. No spermatogonia type A could be detected. In spite of comparable mitotic rates in the Sertoli cells of the experimental and control mice and more dark Sertoli cells with well developed smooth endoplasmic reticulum (SER) in the experimental mice, one of the functions of fetal Sertoli cells was suppressed: there were fewer dark slender Sertoli cells with long processes extending to the centers of tubules and more contact areas with gonocytes, phenomena which may play a role in the migration of gonocytes towards the periphery of the tubules. More Sertoli cells were detected in the undescended than the descended testes exposed to the highest dose of EE. These morphological findings indicate that prenatal exposure to EE induces acceleration of prespermatogenesis and disturbances in the initiation of spermatogenesis and in the mechanical function of Sertoli cells. PMID- 2876661 TI - Three-dimensional reconstruction of a small-granule paracrine cell cluster in an adult hamster bronchus. AB - Amine precursor uptake and decarboxylation (APUD) small-granule cells were stained by periodic acid-Schiff (PAS)-lead hematoxylin in 0.5-micron etched Epon sections of adult hamster lung fixed for transmission electron microscopy. The leading edge of a small-granule cell cluster was identified in a segmental bronchus as a single PAS-positive cell. From 256 serial thin sections through its entirety, a three-dimensional wooden reconstruction of the cluster and morphometric estimates of the apical and basal surfaces, cell volume, and intracytoplasmic distribution of mitochondria and small granules was made. Of moderate size, the body consisted of 16 small-granule cells, 11 forming its ovoid core with five outlying cells diverging at the margin; these were pyramidal, possessing wide bases and thin apical processes. At the bronchial surface, processes from the 11-cell core emerged together, whereas the divergent cells emerged in groups of two and three. Ten Clara-like cells and one ciliated cell encircled the core. Altogether they formed a pseudostratified epithelium in contrast to the surrounding simple columnar epithelium. Deeper in the cluster, numerous cytoplasmic extensions interdigitated with those from adjacent cells, and toward the base the Clara-like and APUD cells were increasingly interposed. In marked contrast to the apical cytoplasm, the infranuclear cytoplasm of the latter was densely packed with ca. 1,000 A electron-dense granules; and the basal, presumptively secretory face of each cell was five to six times greater than the area exposed to the bronchial lumen. Judged by granule size and ultrastructure, only one APUD cell type was recognized in the reconstructed cluster. Beneath it many fibrocytic processes were separated from the APUD cells by only the thickness of the basal lamina. Two fascicles of smooth muscle approached the cluster within 0.4-0.8 micron. Unmyelinated nerve fibers came as close but contacted only the muscle. Capillaries, in contrast, came no closer than 15 micron from the base of the body. Evidently, 1) fibrocytes and smooth muscle are more likely targets for secretions from such a paracrine body than cells reached through the blood-stream, and 2) not all small-granule cell clusters are innervated. PMID- 2876660 TI - Immunohistochemical evidence for extrinsic and intrinsic opioid systems in the guinea pig superior cervical ganglion. AB - Immunohistochemical localization of the opioid peptides alpha-neo-endorphin (alpha-neo-END), dynorphin A (DYN) and leu-enkephalin (leu-ENK) in the guinea pig superior cervical ganglion (SCG) was studied following central denervation, peripheral axotomy, and after application of the depleting drug reserpine and of the neurotoxin 6-hydroxydopamine. The paraganglionic cells of the SCG are shown to form an intrinsic opioid--(alpha-neo-END, DYN, leu-ENK)--immunoreactive system being not visibly responsive to the experimental procedures. Leu-ENK immunoreactive fibres ascend in the preganglionic trunk and supply fibre baskets to defined clusters of postganglionic neurones. Principal ganglion cells of the SCG containing alpha-neo-END- and DYN-immunoreactivity project to extraganglionic targets via the postganglionic nerves. These findings are indicative of a sympathetic alpha-neo-END-ergic and DYN-ergic innervation of effector organs. They also point to a modulatory function of opioids on neuronal activity in a paravertebral ganglion. PMID- 2876662 TI - Pharmacokinetics and placental transfer of intravenous and epidural alfentanil in parturient women. AB - Alfentanil was administered as a 30 micrograms/kg single intravenous injection to five healthy women scheduled for elective cesarean section (group A). In five pregnant women normal vaginal delivery was supported by epidural analgesia with a 30 micrograms/kg loading dose followed by a 30 micrograms/kg-1/hr-1 infusion of alfentanil (group B). Five healthy nonpregnant women scheduled for minor general surgery received 120 micrograms/kg alfentanil intravenously as a bolus before surgical incision (group C). In groups A and B plasma alfentanil concentrations, alfentanil plasma protein binding, and alpha 1-acid glycoprotein (alpha 1-AGP) concentrations were measured in maternal and umbilical arterial or venous blood samples at delivery. Multiple arterial sampling in groups A and C for measurement of alfentanil plasma concentration decay analysis indicated three-compartmental characteristics in most patients. In the pregnant population terminal half-life (t1/2 beta), volume of distribution at steady state (Vdss), and total plasma clearance (Clp) amounted to 103 +/- 67 min, 541 +/- 155 ml/kg and 6.48 +/- 0.85 ml/kg-1/min-1, respectively (mean +/- SD), and did not differ significantly in nonpregnant patients. In groups A and B the fetal-maternal ratios indicated a concentration gradient for the total plasma alfentanil content (ratio of total alfentanil concentrations in umbilical venous and maternal blood (Uv/M), 0.31 +/- 0.08 and 0.28 +/- 0.06 (mean +/- SD) in groups A and B respectively) with a larger protein binding capacity in maternal plasma (group A, 85 +/- 3%; group B, 90 +/- 1%) (mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876663 TI - Rapid-sequence induction: vecuronium versus pancuronium versus succinylcholine? PMID- 2876665 TI - Polymorphic restriction sites in the horse beta-globin gene cluster. AB - Horse DNA samples digested with PstI and probed with the rabbit beta 1 globin gene show three phenotypes determined by one fragment of variable length (about 5.1 or 3.3 kb). Family data demonstrate that these fragments segregate as Mendelian alleles. The frequencies of the two alleles are 0.66 for the 3.3-kb fragment and 0.34 for the 5.1-kb one. Another polymorphism has been detected with BamHI. Again three phenotypes determined by two alleles (fragments of 7.5 and 3.8 kb) have been observed. Allelic frequencies of the 7.5- and 3.8-kb fragments are 0.24 and 0.76 respectively. The two polymorphic sites are non-randomly associated. PMID- 2876664 TI - Antiaggregative aspirin dosage at the affected vessel wall. AB - The present study, using patients with Takayasu's disease (pulseless disease), characterized by segmentally affected arterial lesions and stenotic conditions with a nonspecific inflammatory morbid condition, was designed to assess whether or not a low dose of aspirin can practically exert its preventive effect against the aggregation of platelets that have just passed along a rough-surfaced arterial wall. Twenty Japanese women with Takayasu's disease were selected under the following criteria: A unilateral upper extremity was angiographically confirmed to be affected with the disease, while the contralateral limb was almost normal. Systolic blood pressure on the affected side was almost half that on the nonaffected side. The patients showed neither a positive CRP nor an accentuated ESR. In these patients, mean plasma levels of TXB2 and 3 microM ADP induced platelet aggregation in blood obtained from the affected side were 156.5 +/- 17.7 pg/ml, and 59.5 +/- 6.0%, respectively, which were significantly high as compared with 104.5 +/- 17.6 and 41.7 +/- 8.8%, respectively, in samples from the nonaffected side. Forty and eighty mg of aspirin per day administered to two randomly composed groups, respectively, showed an improvement in platelet aggregability and TXB2 levels on the nonaffected side. In the affected limbs, though 80 mg/day led to significant decreases in TXB2 levels (108.0 +/- 7.8 pg/ml, p less than 0.05) and platelet aggregability (21.3 +/- 7.6%), the 40-mg regimen showed no significant reductions (134.6 +/- 9.4 pg/ml, 35.6 +/- 17.1%). Plasma levels of 6-keto PGF1 alpha revealed no differences between 40- and 80-mg regimens, or between before and after treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876666 TI - The effect of systemic beta-2 adrenergic agonist therapy on the pulmonary hypertensive response to chronic hypoxia in rats. AB - Chronic hypoxia produces polycythemia, pulmonary hypertension, muscularization of peripheral pulmonary arteries, and right ventricular hypertrophy. The present study was designed to investigate the effects of systemic administration of a beta-2 adrenergic agonist on these responses. Male Wistar rats (9 or more in every group) were maintained in room air or 10% oxygen for 28 days. In the first experiment, they were treated with albuterol at various doses (0.05 mg/kg, 0.1 mg/kg, 0.5 mg/kg) twice during exposure to intermittent hypoxia (10 h/day). In the second experiment, rats were treated with albuterol 2.5 mg/kg subcutaneously twice daily during continuous hypoxia. Control animals in normoxia and hypoxia received 0.1 ml saline at equivalent times. All hypoxic groups developed polycythemia, significantly increased right ventricular systolic pressure, and right ventricular hypertrophy. At doses of albuterol that did not produce cardiac hypertrophy in normoxia, treatment had no effect on the development of right ventricular hypertrophy. With lower doses of albuterol in hypoxia, there was a trend towards an increase in hematocrit, but overall this did not reach significance. Treatment with high dose albuterol in continuous hypoxia significantly increased the hematocrit and enhanced the remodeling of the pulmonary vasculature (Hematocrit: saline-treated, 57.7 SEM 1.9; albuterol treated, 63.4 SEM 1.7; p less than 0.05. Percentage of thick-walled peripheral vessels: saline-treated, 19.4 SEM 0.60; albuterol-treated, 22.7 SEM 0.85; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876667 TI - Hypercalcemia in squamous cell carcinoma of the renal pelvis? Parathyroid or paraendocrine in origin. AB - Hypercalcemia associated with metastatic cancer may be due to osteolytic invasion or paraendocrine effects of the neoplasm. A patient with refractory hypercalcemia of long duration underwent cervical parathyroid exploration; three glands were found, but hypercalcemia persisted. After localization studies, a fourth gland was uncovered from the mediastinum. Hypercalcemia persisted, and at operation for kidney stones, squamous cell carcinoma of the renal pelvis was discovered, which progressed to cause the patient's death in hypercalcemia. PMID- 2876668 TI - Spontaneous intrahepatic hemorrhages in polyarteritis nodosa. PMID- 2876669 TI - Prevention of duodenal ulcer recurrence. AB - Recurrent duodenal ulcers, treated with cimetidine, 400 mg, or ranitidine, 150 mg, once nightly, or with sucralfate, 1 g twice daily, can be prevented in approximately 75% of patients for up to 1 year. Because these drugs are generally of equal efficacy, the choice is based on the patient's previous drug experience and tolerance, potential side effects, risk of drug interaction, frequency of administration, and cost. These medications do not alter the natural history of duodenal ulcer disease, and therapy may need to continue for longer than 1 year if there are no long-term side effects. Extra efforts should be made to help cigarette smokers discontinue smoking. Patients who have recurrent duodenal ulcers during maintenance therapy can be retreated with full-dose therapy. If optimal drug therapy is unsuccessful in preventing frequent recurrences or complications, surgical treatment is indicated. PMID- 2876670 TI - Von Recklinghausen's disease with pheochromocytoma and nonmedullary thyroid cancer. PMID- 2876671 TI - H2 antagonists and the common cold. PMID- 2876672 TI - [Memory gaps and hypercomplex automatisms after a single oral dose of benzodiazepines: clinical and medico-legal aspects]. AB - From 8 original observations and from an overview of published cases, the authors make out two kinds of mental disorders connected with benzodiazepines use: 1) transient global anterograde amnesia; 2) amnesic complex automatism. Consequences for forensic medicine are finally investigated. PMID- 2876673 TI - Plasma bile salt levels and liver disease. PMID- 2876674 TI - [Proteolytic events in the maturation of pro-neuropeptides. The somatostatin model]. AB - The post-translational processing (maturation) of the precursors was studied on the model of the prosomatostatin. We have shown the presence of a single and common precursor to both somatostatin -28 and -14 in mouse hypothalamus, in contrast with the situation in the Teleostean fish, Lophius piscatorius. The search for a maturation activity was carried out using a synthetic undecapeptide substrate including in its sequence the cleavage site for somatostatin-14 release. Using this peptide, we characterized in rat brain cortex extracts a specific enzyme activity of 90 kD. This "maturase", colocalized in the neurosecretory granules with the somatostatin products, generates both the N terminal peptide S-28, and the tetradecapeptide hormone (S-14) from the somatostatin-28, acting as a "S-28 convertase" producing free Arg and Lys residues present at the pair of basic amino acids signal. We propose a model where three peptide bonds are cleaved by this enzymatic activity. In the teleostean fish: Lophius piscatorius, two precursors coding for two different somatostatin were predicted by the determination of cDNA sequence. In this system, we observed the presence of a unique form of the tetradecapeptide hormone. We show that the final maturation product of the second precursor is a new 28 amino acid hormone called Somatostatin-28 II. Moreover, the product of this second gene after the action of the Somatostatin-28 convertase from rat brain cortex is the (Tyr7, Gly 10)S-14 derivative predicted by the clone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876675 TI - [Strategies for detecting restriction polymorphisms of Y chromosome sequences]. AB - Six cloned genomic sequences from the human Y chromosome were used for the detection of restriction polymorphisms in a panel of unrelated DNAs. Three sorts of strategies for the detection of polymorphisms were used: (a) mixing individual DNAs restricted by several endonucleases, (b) separated restrictions of the DNA library members with six different restriction enzymes, (c) individual DNA digestion with TaqI and MsqI. Results show that restriction polymorphisms are detected only rarely; this result can be explained by exemption of most of the Y chromosome from meiotic pairing and exchange. PMID- 2876676 TI - [Methodological approaches to the rapid determination of the sensitivity of the causative agent of gas gangrene to antibiotics]. AB - The results of the studies on development of a rapid assay of antibiotic sensitivity of gas gangrene causative agents with their high nutrient requirements under obligatory anaerobiosis are summarized. The data on development of a uniform standard nutrient medium with the use of dry components made in the USSR are presented for the first time. The medium is intended for rapid assay of antibiotic sensitivity of the main causative agents of gas gangrene, i.e. C. perfringens, C. oedematiens, C. histolyticum and C. septicum. PMID- 2876678 TI - Changes in the cell wall of Clostridium species following passage in animals. AB - Morphological changes in clostridial isolates after animal passage with other flora in mixed infections were studied by utilizing a subcutaneous abscess model in mice. We used 26 isolates of 7 clostridial species, and one isolate each of Bacteroides fragilis and Klebsiella pneumoniae. Abscesses were induced by all 7 Clostridium perfringens and 3 Clostridium butyricum isolates and by some of the other isolates. A thick granular wall prior to animal inoculation was shown only in C. perfringens, C. butyricum, and C. difficile. This structure was observed in other clostridia only following their animal passage alone or when co-inoculated with K. pneumoniae or B. fragilis. PMID- 2876677 TI - Biochemistry and clinical applications of ribavirin. PMID- 2876679 TI - Enterotoxin synthesis by nonsporulating cultures of Clostridium perfringens. AB - Chemostat-cultured Clostridium perfringens ATCC 3624 and NCTC 10240, and a nonsporulating mutant strain, 8-5, produced enterotoxin in the absence of sporulation when cultured in a chemically defined medium at a 0.084-h-1 dilution rate at 37 degrees C. The enterotoxin was detected by serological and biological assays. Examination of the chemostat cultures by electron microscopy did not reveal sporulation at any stage. The culture maintained enterotoxigenicity throughout cultivation in a continuous system. The enterotoxin was detected in batch cultures of each strain cultivated in fluid thioglycolate medium and a chemically defined medium. No heat-resistant or light-refractile spores were detected in batch cultures during the exponential growth. PMID- 2876680 TI - Regulation of the mitochondrial ATP synthase/ATPase complex. AB - The mitochondrial ATP synthase/ATPase (F0F1 ATPase) is perhaps the most complex enzyme known. In animal systems it consists of a minimum of 11 different polypeptide chains, 10 (or more) of which appear to be essential for function, and 1 called the "ATPase inhibitor peptide" which is involved in regulation. Recent studies from a variety of laboratories indicate that the ATP synthase/ATPase complex is regulated by several interrelated factors including the thermodynamic poise of the proton gradient across the inner mitochondrial membrane; the ATPase inhibitor peptide; ADP (and/or ADP and Pi); divalent cations; and perhaps the redox state of SH groups on the F1 molecule. The central focus of this review is the ATPase inhibitor peptide. A model involving four distinct conformational states of F1 seems essential to account for the inhibitor's mode of action. The model depicts the ATPase inhibitor protein as acting at the asymmetric center of the F1 moiety. In addition, it accounts for the "unidirectional" role of the inhibitor peptide as a "down regulator" of ATP hydrolysis and for its binding/debinding dependence on the proton motive force and other regulatory factors. Finally, it is suggested that during any physiological process, where there is an energy demand followed by a resting phase, the F1 molecule may follow a "cyclic" path involving the four distinct conformational states of the enzyme. PMID- 2876681 TI - Organization of the pathway of de novo pyrimidine nucleotide biosynthesis in pea (Pisum sativum L. cv Progress No. 9) leaves. AB - The organization of the enzymes of de novo pyrimidine nucleotide biosynthesis in pea (Pisum sativum L. cv Progress No. 9) has been studied. The first three enzymes of the pathway, carbamoyl-phosphate synthetase, aspartate carbamoyltransferase, and dihydroorotase, are readily separable from one another; they are not part of a multifunctional complex. The final two activities of the pathway, orotate phosphoribosyltransferase and orotidylate decarboxylase, copurify and appear to be complexed in vivo. This organizational pattern is distinct from those reported for bacteria, yeast, and mammals. The differences in organization, in a pathway which is present in all organisms, make the pyrimidine biosynthetic pathway a very interesting candidate for evolutionary studies. PMID- 2876682 TI - [Fragmentation of calculi with lasers]. PMID- 2876683 TI - Neutropenia in patients with inflammatory arthritis treated with sulphasalazine. AB - This report describes two patients who developed severe neutropenia one month after starting sulphasalazine (SASP) as treatment for their inflammatory joint disease. Both recovered on stopping the drug. Six further cases (out of a series of 180 patients with inflammatory forms of arthritis receiving SASP therapy) in whom transient leucopenia occurred are also recorded. These patients were able to continue the drug under close supervision. Sulphasalazine is a useful addition to the small number of slow acting antirheumatic drugs (SAARDs) and, despite this complication, is safer than other SAARDs. Careful monitoring of patients is essential, however, particularly in the early stages of treatment, to detect this adverse reversible reaction promptly. PMID- 2876684 TI - Regional hemodynamic effects of the beta-adrenoceptor blockers tertatolol and propranolol in conscious spontaneously hypertensive rats. AB - The effects of the beta-adrenoceptor blocking drugs propranolol and tertatolol on regional hemodynamics were studied in conscious spontaneously hypertensive rats (SHR). Regional blood flows were measured using a 20 MHz directional pulsed Doppler system with miniaturized Doppler probes on the left renal artery, the superior mesenteric artery and the abdominal aorta. This allowed the determination of changes in resistances in the renal (RR), mesenteric (MR) and hindquarter (HQR) vascular beds. Tertatolol and propranolol caused an immediate fall in heart rate. Mean arterial pressure (MAP) increased during the first 15-30 min following injection of the beta-blockers. Thereafter it gradually fell below control values to reach significant decreases in MAP 3-4 hr following injection. Fifteen to thirty min after propranolol, vascular resistances increased in all 3 vascular beds significantly. Resistances returned to control values over the next 3-4 hr. Following tertatolol, HQR increased significantly during the first 15-30 min. MR and RR did not increase significantly whereas a significant fall in RR was observed after 3-4 hr. These data indicate different regional hemodynamic effects for tertatolol and propranolol in the conscious SHR. Tertatolol does not cause the renal and mesenteric vaso-constriction observed following propranolol. PMID- 2876685 TI - Pharmacological study of basal acid secretion by the rat isolated fundus preparation. AB - The rat isolated stomach preparation secretes acid in the absence of exogenous stimulants. This basal secretion of acid was unaffected by high concentration of antagonists to stimulated secretion in this preparation and by TTX. Basal secretion was inhibited by omeprazole (10(-7)-10(-5) M), KSCN (10(-4)-10(-2) M) and to a lesser extent by somatostatin (10(-6)-10(-5) M) but not by verapamil (3 X 10(-4) M), nifedipine (3 X 10(-4) M) and trifluoperazine (10(-3) M). Two long acting H2-antagonists, oxmetidine and SKF 93479 (10(-5)-10(-4) M) inhibited basal secretion by a mechanism not involving an action at H2-receptors. It is concluded that basal secretion in this in vitro preparation is independent of the endogenous release of known stimulants of acid secretion and activity of the intrinsic nervous system. PMID- 2876686 TI - Inhibition of gastric acid secretion by H2-receptor antagonists. AB - Wy-45,086 and Wy-45,253, synthesized as potential antiulcer agents, were shown by in vitro and in vivo evaluation to have potent H2-receptor antagonist activity (respective pA2's of 8.1 and 7.6), and to have gastric acid antisecretory activity (respective ED50's of 1 and 2 mg/kg in the pylorus-ligated rat and of 1 and 1.4 mg/kg in dogs prepared with innervated gastric pouches). Both compounds were significantly more potent than ranitidine and cimetidine. PMID- 2876687 TI - Interaction of beta-adrenergic antagonists with local anaesthetic acceptor sites. AB - H3-dihydroalprenolol (H3-DHA) binding in isolated smooth muscle cells has been studied. Two different binding sites have been detected: a high affinity (highly specific) and a low affinity (nonspecific) binding site. Local anaesthetics are able to displace H3-DHA from nonspecific sites with a rank order of potency that mirrors their local anaesthetic activity. This finding correlates, at the molecular level, with the local anaesthetic properties of beta-blockers, as concluded from classical pharmacological experiments. PMID- 2876688 TI - Study on the anticonvulsant activity of clonidine against pentylenetetrazol induced seizures in rats: pharmacological evidence of alpha 2-adrenoceptors mediation. AB - The present work deals with an EEG and behavioral study of the interaction of alpha-adrenoceptor antagonists on the anticonvulsant activity of clonidine against the convulsions due to pentylenetetrazol (PTZ) in rats. Clonidine's ability (0.5 mg/kg, i.p.) to inhibit the tonic seizures and mortality induced by PTZ (75 mg/kg, i.p.) was counteracted by pretreatment with yohimbine and mianserine (10 mg/kg, i.p.). On the contrary, prazosin (10 mg/kg, i.p.) did not influence the anticonvulsant effect of clonidine. The results suggest that central alpha 2-adrenoceptors play an important role in the control of motor and EEG convulsions elicited by PTZ. PMID- 2876690 TI - In vitro evaluation of the beta-blocking and electrophysiological properties of mepindolol. AB - The electrophysiological and beta-blocking effects of mepindolol have been examined in isolated guinea-pig preparations and sheep cardiac Purkinje fibers. Mepindolol did not show selectivity for blocking the chronotropic and inotropic responses to isoprenaline on isolated guinea-pig preparations, and was practically equally potent in blocking the effect of isoprenaline on isolated guinea-pig trachea. Mepindolol 10(-7) M fully antagonized the positive chronotropic effect of isoprenaline (10(-7) M) in Purkinje fibers. However, normal automaticity, action potential characteristics, effective refractory period, membrane responsiveness of Purkinje fibers were unaffected by mepindolol up to 10(-6) M. On the whole, mepindolol appears to be a potent beta-blocker with no cardioselectivity, exerting membrane depressant effect only at concentrations 100-1000 times higher than those exerting effective beta-blockade. PMID- 2876689 TI - Pharmacological effects of nalorphine and nalorphine-7,8-oxide (nalorphine epoxide): interaction of the intrinsic activity, affinity and pharmacological responses. AB - We examined the relationship between the pharmacological effects and the interactions of the receptors of nalorphine and its epoxide. The abilities of nalorphine-epoxide to displace [3H]-dihydromorphine (mu-site) and [3H] ethylketocyclazocine (kappa-site) were practically equal to those of the parent compound, nalorphine, using binding assay to the rat brain membrane preparations. Furthermore, the affinities of mu- and kappa-receptors are virtually uninfluenced by epoxidation of the 7,8-double bond of nalorphine using electrically stimulated mouse and rabbit vasa deferentia. The intrinsic activity of nalorphine, however, is considerably decreased by epoxidation. Moreover, the antagonistic effect of nalorphine to the morphine-induced antinociception (via mu-receptors) was little influenced by epoxidation, but the antinociceptive effect of nalorphine using the acetic acid writhing test was considerably reduced by epoxidation. These results suggest the presence of a higher receptor capacity for the antinociception mediated through kappa-receptors and that the differences between the pharmacological responses of nalorphine and its epoxide are due to the differences of their intrinsic activities. PMID- 2876691 TI - Effects of dl-methadone on the response to physiological transmitters and on several functional parameters of the isolated guinea-pig heart. AB - The effects of high concentrations of dl-methadone (1-10 microM) on several parameters of cardiac function were studied in isolated guinea-pig heart preparations. The opioid agonist dose-dependently potentiated the inotropic cardiac response to sympathetic nerve stimulation; this effect was naloxone insensitive and was antagonized by an increase in extracellular calcium concentration. Moreover, methadone enhanced the dose-inotropic response curve of exogenous noradrenaline. The cardiac response to parasympathetic stimulation was antagonized by the drug through a postsynaptic effect; the responses to histamine and isoprenaline were also antagonized in a noncompetitive way. The spontaneous rate and contractility of atrial preparations were depressed by methadone concentrations above 1 microM; the functional refractory period was increased and the maximal driving rate was reduced at the same range of concentrations. All the above mentioned effects were naloxone-insensitive. In isolated sheep Purkinje fibers methadone, at concentrations of 10 microM and higher, significantly affected the transmembrane action potential parameters, by chiefly decreasing the maximum rate of depolarization and increasing the action potential duration. It was concluded that high concentrations of dl-methadone are able to affect several parameters of cardiac function through an unspecific mechanism different from the stimulation of opiate receptors. PMID- 2876692 TI - Calcitriol levels in hypercalcemic patients with adult T-cell lymphoma. AB - Hypercalcemia is a frequent complication in patients with adult T-cell lymphoma. We measured serum calcitriol (1,25-dihydroxyvitamin D3) levels in five hypercalcemic patients with adult T-cell lymphoma and compared the values with those of five patients with mycosis fungoides, a T-cell neoplasm not associated with hypercalcemia. All five patients with adult T-cell lymphoma had calcitriol levels in or below the normal range. These data show that elevated calcitriol levels are not uniformly elevated in this disorder and may not be the usual cause of hypercalcemia in this subgroup of patients with lymphoma. PMID- 2876693 TI - [Drugs as markers in identification. Detection of melperon (Buronil) in an adipoceratous corpse]. AB - The body of a 76-year old female pensioner was recovered from the Danube as adipoceratous torso after the person had been missing for almost two years. Identification first of all based on comparing postmortem and radiological findings which revealed correspondence of numerous features. The missing woman had been receiving long-term drug therapy of melperone (active substance of the neuroleptic Buronil) in doses of 25 mg three times daily. Combined gas chromatography and mass spectrometry succeeded in detecting the characteristic mass fragment of melperone in the adipoceratously transformed bone marrow of the water-logged corpse; in the remaining soft tissues outside the bones the concentration was below detection range. The reported case exemplifies that demonstration of low drug levels resulting from therapeutic ingestion can contribute to the identification of extensively decomposed bodies and to the correct relating of severed parts. PMID- 2876695 TI - Studies on histaminergic compounds, III. Synthesis and histamine H2-activity of a series of corresponding histamine and dimaprit analogues. PMID- 2876694 TI - Ether derivatives of 3-amino-1,2-propanediols, V. Syntheses and pharmacological activities of 5-(cycloalkoxymethyl)oxazolidines and N-substituted derivatives. PMID- 2876696 TI - Hay fever--a distressing environmental allergy. From the Royal Melbourne Hospital Pharmacy Department. PMID- 2876697 TI - Clinical and pathological responses of sheep and cattle to experimental infection with five different viruses of the epizootic hemorrhagic disease of deer serogroup. PMID- 2876698 TI - Necrotic enteritis in cage-reared commercial layer pullets. AB - Necropsy of five 12-week-old pullets from a flock of 99,300 suffering from an increased mortality rate revealed enlarged, gas-filled intestines, the mucosal surfaces of which had the "dirty turkish towel" appearance typical of necrotic enteritis. Although the pullets had been raised entirely in cages, intestinal scrapings revealed the presence of Eimeria maxima. Histopathological findings were compatible with necrotic enteritis. Clostridium perfringens was isolated by anaerobic culture from the intestines. Mortality returned to normal after bacitracin and amprolium were added to the feed. PMID- 2876699 TI - Mental phenomena as changes of state in a finite-state machine. AB - This paper examines the classical functions of the psyche--cognition, affection and conation--from a phenomenological viewpoint and finds them to be defined each in terms of the other. It is held that this circularity of definition reflects the fundamental unity of conscious experience and, as a consequence, that the search for the biological substrate underlying individual functions too readily degenerates into a morphological and biochemical phrenology. An alternative approach, based on considerations from the field of artificial intelligence, is discussed. This approach provides a description of mental phenomena as changes of state in a finite-state machine, the next state being determined by both previous states and current inputs. This concept is shown to be compatible with the descriptions of conscious experience outlined in the phenomenology of Karl Jaspers. It is suggested that neurobiological investigations should be directed towards defining the processes by which state changes occur and further seeking to define mental pathology as aberrations of these dynamic processes. PMID- 2876700 TI - A study of the need for anticholinergic medication in patients treated with long term antipsychotics. AB - Studies on the withdrawal of anticholinergics from patients on antipsychotics have produced conflicting results. This 12-week study employed a double-blind crossover design on 39 adult in-patients selected from a total hospital population of 620. The Colombia Scale was used to determine extrapyramidal side effects (EPS). All patients were stabilised prior to the study on benztropine mesylate 2 mg b.i.d., and gradual withdrawal was employed. Benztropine withdrawal produced a significant increase in overall EPS scores. Ten patients (26%) required reinstatement of benztropine while on placebo. Sialorrhoea, rigidity and postural instability were the most prominent changes. Neither age, sex, nor diagnosis were significantly predictive of EPS. Depot medications and doses greater than 1000 mg/day chlorpromazine-equivalent were related to significant EPS increase. The intrinsic anticholinergic properties of the antipsychotics themselves and concomitant medications, such as antidepressants, appeared protective against development of EPS. Most patients on a combination of antipsychotics and anticholinergics can safely be withdrawn from the latter. PMID- 2876701 TI - [Behavior of GOT, GPT and gamma-GT enzymes in healthy probands before and after acute alcohol burden]. PMID- 2876702 TI - No synergism between ionomycin and phorbol ester in fatty acid synthesis by isolated rat hepatocytes. AB - With hepatocytes in suspension, freshly isolated from meal-fed rats, no significant effect of ionomycin on the rate of de novo fatty acid synthesis was observed, whereas phorbol myristate acetate (PMA) was strongly stimulatory. The combination of ionomycin and PMA produced the same stimulation as was seen with PMA alone. Stimulation of fatty acid synthesis by vasopressin was comparable and not additive to that observed with PMA, indicating that activation of protein kinase C is solely responsible for this metabolic effect of vasopressin. Both vasopressin and PMA increased acetyl-CoA carboxylase activity in isolated rat hepatocytes. PMID- 2876703 TI - Atrial natriuretic factor induced phosphorylation of human placental membrane protein: an effect mimicked by guanosine 3':5'-cyclic monophosphate. AB - Atrial natriuretic factor (ANF) specifically stimulated the endogenous phosphorylation of a protein band in an isolated membrane fraction of human placenta. The apparent molecular weight of the substrate protein as determined by SDS-polyacrylamide gel electrophoresis is 160-170,000. In the same membrane fraction, ANF also stimulated guanylate cyclase activity in a dose-dependent manner. Guanosine 3':5'-cyclic monophosphate (cyclic GMP), added to the membrane fraction in lieu of ANF, also stimulated the phosphorylation of several protein bands, one of which have the same apparent molecular weight as the one stimulated by ANF. In contrast, adenosine 3':5'-cyclic monophosphate (cyclic AMP) at a similar concentration and hormones such as angiotensin II, insulin and vasopressin had no effect on the phosphorylation state of this protein band. The finding that ANF alters the phosphorylation state of a certain membrane protein and that this effect is mimicked by cyclic-GMP suggests that at least some of the biological action of ANF may be mediated by the phosphorylation of membrane protein involving a cyclic GMP-dependent protein kinase. PMID- 2876704 TI - Unmasking of the inhibitory action of glucose on insulin release after alpha 2 adrenergic activation. AB - Insulin release in response to glucose was measured after culture of islets from ob/ob-mice in a Ca2+-deficient medium. The stimulatory effect of 20 mM glucose disappeared after addition of 1 microM L-epinephrine, and it was reversed into inhibition when the medium contained 0.1 to 10 microM clonidine. Glucose inhibited insulin release also after activation of the alpha 2-adrenoceptors with B-HT 933, whereas blocking of these receptors with idazoxan removed glucose inhibition in the presence of clonidine. It is concluded that alpha 2-adrenergic activation provides an efficient means of unmasking the inhibitory component in the action of glucose on insulin release. PMID- 2876705 TI - Somatostatin inhibits fusion of pituitary secretion vesicles with the plasma membranes. AB - Somatostatin has been found to inhibit secretion vesicle fusion with the iodinated (125-I) inside-out plasma membrane vesicles (both were isolated from the anterior pituitaries). This effect of somatostatin was specific and dose dependent (half-maximal effect at 10(-9) M). Calmodulin (10 microM), but not cyclic AMP, enhanced the fusion process between the two organelles and somatostatin inhibited calmodulin-stimulated fusion. These observations suggest that one facet of somatostatin action on hormone secretion may be its inhibition of secretion vesicle fusion with the plasma membrane. PMID- 2876706 TI - Chemical cross-linking of somatostatin receptors in rat adrenal cortex. AB - Adrenocortical somatostatin receptors have been shown to interact with somatostatin-14 (S-14) and somatostatin-28 (S-28). To determine whether these peptides interact with the same or different receptor proteins, we chemically cross-linked these receptors using disuccinimidyl suberate to radioligands prepared from tyrosinated S-14 and S-28 analogs. Sodium dodecylsulfate polyacrylamide gel electrophoresis and subsequent autoradiography of [125I-Tyr11] S-14 and [Leu8, D-Trp22, 125I-Tyr25] S-28 cross-linked to their binding sites following solubilization in the presence of 50 mM DTT revealed the presence of a single labelled protein of Mr = 200,000. When the cross-linked material was treated under non-reducing conditions, this band was not observed. Furthermore, addition of excess S-14 and S-28 at the time of binding inhibited the incorporation of both radioligands into the receptor protein. These results demonstrate that adrenocortical membrane receptors for somatostatin contain a single receptor protein sub-unit or sub-units of identical size which interact with both S-14 and S-28. PMID- 2876707 TI - Glyburide action in cultured 3T3-L1 adipocytes. AB - During adipocyte differentiation of 3T3-L1 cells, glyburide increased the specific activity (mU/mg protein) of glycerol-3-P dehydrogenase (by at least 14 fold) and glutamine synthetase (by 5-fold). The glyburide-mediated increases in enzyme activities were greater in the presence than in the absence of insulin. Our data indicate that glyburide either potentiates or mimics the actions of insulin to increase the activity of glycerol-3-P dehydrogenase during adipocyte differentiation of cultured 3T3-L1 cells. PMID- 2876708 TI - The effect of neuroleptics on imipramine demethylation in rat liver microsomes and imipramine and desipramine level in the rat brain. AB - A study of the cytochrome P-450 level and imipramine (IMI) demethylase activity in liver microsomes of rats treated concurrently with IMI and chlorpromazine (CPZ) or IMI and chlorprothixene (CPX) for two weeks were carried out. Concomitant administration of IMI and CPZ or IMI and CPX elevated the cytochrome P-450 level and accelerated IMI demethylation in in vitro study. Kinetic study of IMI demethylation carried out in the absence or in the presence of CPZ or CPX revealed that those neuroleptics inhibited IMI demethylation via competitive mechanism. Simultaneously with the enzymatic study the brain level of IMI and its demethylated metabolite desipramine (DMI) was assessed. It was found that 1 hr after withdrawal of IMI and CPZ or IMI and CPX the brain level of IMI was elevated in comparison with that of IMI treated animals, and the ratio between DMI/IMI brain concentration was decreased. When the assessment of IMI and DMI brain level was performed 24 hr after withdrawal of IMI and CPZ or IMI and CPX, there was no difference between the concentration of IMI and DMI in both, experimental and control animals. PMID- 2876709 TI - Heterogeneity between soluble human and rabbit splenic alpha 2-adrenoceptors. AB - The pharmacological and biochemical characteristics of soluble alpha 2 adrenoceptors were investigated to determine whether differences observed in membranes were maintained in solution and to probe the nature of any such differences. alpha 2-Adrenoceptors were solubilized from purified plasma membrane preparations of human and rabbit spleen using digitonin. [3H]yohimbine bound to one population of alpha 2-adrenoceptors in the preparations with dissociation constants of 2.4 nM and 7.8 nM respectively. The pharmacological profile of the alpha 2-adrenoceptors has been examined. Upon solubilization the affinity of the alpha 2-adrenoceptors for yohimbine was unchanged. In contrast, the potency of idazoxan and RX 811066 were increased, whereas the potency for prazosin (human only), phentolamine and WY 26392 was decreased 2-3-fold. The potency of the agonists oxymetazoline, UK 14304 and adrenaline were all reduced upon solubilization of alpha 2-adrenoceptors. The selectivity of yohimbine, idazoxan, RX 811066 and WY 26392 for human rather than rabbit alpha 2-adrenoceptors was maintained in solution. Possible sources of heterogeneity between human and rabbit alpha 2-adrenoceptors were investigated. The protein structure was probed by comparing the susceptibility of the receptors to inactivation by sulphydryl modifying agents. No differences were observed in the potency of N-ethylmaleimide or p-chloromercuribenzoate to inactivate the receptor. The carbohydrate component of the receptors was investigated using agarose-linked lectins. Rabbit splenic alpha 2-adrenoceptors had a lower affinity for the lectins wheatgerm agglutinin (Triticum vulgaris) and soybean (Glycine max) which bind the sugars N-acetyl d glucosamine and N-acetyl d-galactosamine respectively. These findings suggest that heterogeneity of the alpha 2-adrenoceptor derives from its structural characteristics rather than its environment in the membrane. PMID- 2876710 TI - Desensitization to nitroglycerin in vascular smooth muscle from rat and human. AB - Guanylate cyclase in high speed supernatant fractions obtained from rat thoracic aorta or human coronary arteries pretreated with nitroglycerin exhibited a marked desensitization to activation by nitroglycerin, nitroprusside, and nitric oxide. However, activation of soluble guanylate cyclase by arachidonic acid was unaffected by pretreatment of vessels with nitroglycerin. Furthermore, activation of soluble guanylate cyclase by protoporphyrin IX was increased 4-fold when vessels were pretreated with nitroglycerin. Soluble guanylate cyclase partially purified from nitroglycerin-pretreated rat thoracic aorta by immunoprecipitation with a specific monoclonal antibody exhibited persistent desensitization to nitrate-induced activation. These data suggest that nitroglycerin-induced desensitization of guanylate cyclase to activation by nitrovasodilators represents a stable alteration of the enzyme. In contrast, activation by protoporphyrin IX of guanylate cyclase immunoprecipitated from nitroglycerin pretreated or control vessels was not significantly different. This suggests that the mechanism of protoporphyrin activation of guanylate cyclase is different than the mechanism with nitrovasodilators. Activation of particulate guanylate cyclase by Lubrol-PX, hemin, or atrial natriuretic factor was not significantly different with enzyme prepared from nitroglycerin-pretreated or control vessels from rat and human. Thus, nitroglycerin-induced desensitization of rat thoracic aorta or human coronary artery results in a relatively stable molecular alteration of soluble guanylate cyclase such that the enzyme is specifically less sensitive to activation by nitrovasodilators whereas the effects of other activators of the enzyme are either unchanged or increased. PMID- 2876711 TI - The effect of kainic, quinolinic and beta-kainic acids on the release of endogenous amino acids from rat brain slices. AB - It has been suggested that the neurotoxic properties of quinolinic acid and kainic acid may, at least in part, involve an indirect action on nerve terminals containing glutamate. In the present study it is confirmed that kainate causes the release of endogenous glutamate from rat hippocampal slices, but that quinolinic acid does not share this activity. In addition beta-kainic acid was found to depress the potassium evoked release of endogenous glutamate at relatively high concentrations and this effect may underlie the anticonvulsant properties of this substance. PMID- 2876712 TI - [Synthesis and H2-antagonistic action of N3, N5-substituted 1,2, 4-oxadiazole-3, 5-diamine. 26. H2-antihistaminics]. AB - N5-(3-[3-(1-Piperidinylmethyl)phenoxy) phenoxy]propyl)-1,2, 4-oxadiazole-3, 5 diamines and N5(2-[(5-dimethylaminomethyl-2-furanyl) methylthio] ethyl)-1,2,4 oxadiazole-3,5-diamines with different N3-substituents were prepared and tested for their H2-antihistaminic activity on the isolated guinea-pig atrium. They were synthesized by nucleophilic substitution of the appropriate 5 trichloromethyloxadiazoles with the amines 3 and 11. Of the prepared substances 10a,c in particular showed high H2-antagonistic activity. PMID- 2876713 TI - Quantitative structure-activity relationships. Fujita-Ban analysis of beta adrenergic blocking activity of 1-phenoxy-3-([(substituted amido)alkyl]amino)-2 propanols. AB - Quantitative structure-activity relationship studies have been performed in a series of 81 beta-adrenergic blocking 1-phenoxy-3-([substituted amido)alkyl] amino)-2-propanols using the Fujita-Ban model. A correlation significant at p less than 0.0005 (r = 0.883, F46,34 = 2.60) was obtained using 46 independent substituents. The set of independent substituents has been successfully contracted to 36 substituents (F 36,44 = 4.26). On the basis of the calculated group contributions the derivatives with high predicted activity have been proposed. PMID- 2876714 TI - Aversive and appetitive properties of anxiogenic and anxiolytic agents. AB - The place-conditioning paradigm was used to assess the appetitive or aversive nature of anxiolytic and anxiogenic drugs. Rats were given a pre-conditioning preference test in which the time that they spent on each side of a two compartment chamber was measured; each side was visually distinct. On two days they were confined to one side immediately after drug injection, and on alternate days they were confined to the other side after vehicle injection. The rats were then given a postconditioning preference test. The change in preference was used as the measure of the reinforcing properties of the drugs. The anxiolytic drugs diazepam, lorazepam, alprazolam, adinazolam, U-43, 465 and tracazolate produced a clear preference for the drug-associated side, indicating the appetitive qualities of these drugs. Preference was less clear for the anxiolytics chlordiazepoxide and buspirone. This suggests that it is possible to dissociate the rewarding and anxiolytic properties of drugs. All the anxiogenic drugs tested (CGS 8216, picrotoxin and yohimbine) produced conditioned aversion. PMID- 2876716 TI - Characterization of a group of transposed human V kappa genes. AB - A genomic region with three V kappa pseudogenes which has been transposed to chromosome 22 is characterized by detailed restriction mapping. A number of subclones are described one of which proved useful to establish an allelic restriction fragment length polymorphism (RFLP) in the region. Allelic and duplication-derived restriction site differences in cosmid clones are discussed with respect to possible problems in genomic walking experiments. PMID- 2876715 TI - Site-site interaction on mitochondrial F1-ATPase. Functional symmetry of the high affinity nucleotide binding sites. AB - Interactions between the high affinity binding sites on mitochondrial F1 were analysed by combined use of the nucleotide analogues 3'-O-(1-naphthoyl)-ADP (N ADP) and 2'-3'-O-(2,4,6-trinitrophenyl)-ADP (TNP-ADP). The binding behaviour of F1 with respect to these ligands was studied by measuring the fluorescence of F1 and of TNP-ADP and the fluorescence anisotropy of N-ADP. A total of 3 high affinity binding sites can be occupied by TNP-ADP. By exchange experiments, it could be shown that binding of TNP-ADP to such a site considerably accelerates the dissociation of a ligand bound to a neighbouring site. These results support the notion that the functional behaviour of F1 is symmetric: during the catalytic cycle any individual site can successively assume different affinity states as has been predicted by hypotheses such as the binding change model. PMID- 2876717 TI - Assay of the glutathione-synthesizing enzymes by high-performance liquid chromatography. AB - We report a new convenient assay of the activity of gamma-glutamylcysteine synthetase (EC 6.3.2.2) and glutathione synthetase (EC 6.3.2.3) in crude microbial extracts as well as in purified enzyme preparations. The assay is based on the quantitative analysis of the reaction products by high-performance liquid chromatography after derivatization of the thiol group with 5,5'-dithiobis-(2 nitrobenzoic acid) as described by J. Reeve, J. Kuhlenkamp, and N. Kaplowitz [(1980) J. Chromatogr. 194, 424-428]. In addition, the procedure yields information on basal levels of gamma-glutamylcysteine and glutathione in crude microbial extracts. The two enzymes responsible for glutathione biosynthesis can be determined in parallel under the same chromatographic conditions. No prior separation from substrates and by-products is necessary. Product formation is linear with time for at least 30 min between 0.03 and 12 mU for both enzymes. Even in crude extracts 0.2-0.5 nmol of products formed can be detected with certainty. The method was found to be sensitive and highly reproducible. PMID- 2876718 TI - Characterization of opioid peptides in the rat stomach. AB - A combination of several chromatographic and assay systems was used to characterize the opioid peptides in rat stomach extracts. Partial purification of opioid material in acetic acid extracts of the corpus plus antrum regions of the rat stomach was carried out by gel filtration chromatography on Sephadex G-50, followed by adsorption onto Amberlite XAD-2 resin. A single peak in opioid activity was determined by both radioreceptor assay (RRA) and bioassay. By high performance liquid chromatography, this peak was resolved into five distinct components, characterized by RRA and (or) radioimmunoassay, with retention times corresponding to methionine enkephalin (met-enk), leucine enkephalin, met-enk arg6-gly7-leu8, met-enk-arg6-phe7, and dynorphin 1-13. Closer examination of the dynorphin component revealed the presence of dynorphins 1-17, 1-13, and 1-8. Trypsin digestion of the partially purified (Sephadex G-50 and Amberlite XAD-2 chromatographed) extract resulted in an overall increase in opioid activity, suggesting the presence of larger, possibly precursor forms. PMID- 2876719 TI - Comparison of infusions of alfentanil or pethidine for sedation of ventilated patients on the ITU. AB - Sedation was studied in 30 patients requiring overnight ventilation in the intensive therapy unit (ITU). Patients received an infusion of either alfentanil or pethidine, supplemented with midazolam. The infusion rates were adjusted to provide optimal sedation as judged by a nurse, and measurements were made of quality of sedation, recovery and serum cortisol concentration. In addition, blood concentrations of alfentanil were measured to permit pharmacokinetic and pharmacodynamic analysis. Satisfactory sedation was achieved in both groups. The required infusion rate for alfentanil was between 0.4 and 0.5 micrograms kg-1 min 1. Recovery was good in both groups, apart from one patient in the alfentanil group, in whom recovery was greatly prolonged and alfentanil pharmacokinetics were abnormal. A difference was found in the metabolic response to surgery between the two groups, the response in the alfentanil group being significantly less marked. PMID- 2876720 TI - Infusion of vecuronium controlled by a closed-loop system. AB - Closed-loop control of neuromuscular blockade, using a semi-continuous infusion of vecuronium, is described. In 28 patients, the average neuromuscular transmission was between 13 and 17% of control. Requirements for vecuronium averaged 1.1 micrograms kg-1 min-1 (0.8-1.5 micrograms kg-1 min-1), being in the same range as for repeated bolus injections. No side effects were observed. After the infusion was stopped recovery was rapid. Only three patients required induced reversal of blockade. PMID- 2876721 TI - Interaction of cyclosporin and its solvent, Cremophor, with atracurium and vecuronium. Studies in the cat. AB - Interactions between Sandimmun (formulated as cyclosporin (CyA) in Cremophor and ethanol) and atracurium or vecuronium were investigated in anaesthetized cats. During stable 50% blockade and with a constant rate of infusion of the neuromuscular blocking drugs, Sandimmun 0.8 mg kg-1 or an equivalent amount of its solvent moiety was injected over 5 min. Sandimmun potentiated the blockade induced by vecuronium (median infusion rate 110 micrograms kg-1 h-1) from 50.7% before injection to maximum 95.2% 17.3 min after injection (median values), whereas the median blockade in cats receiving atracurium (median 250 micrograms kg-1 h-1) increased from 51.3% to 72.4% after 32.9 min. At 45 min after the injection the median blockades were 93.1% and 69.8%, respectively. In cats receiving vecuronium (median 104 micrograms kg-1 h-1) the solvent produced an increase in effect of from 51.1% to maximum 78.0% blockade after 5.4 min and 61.5% after 45 min (median values). Interaction with solvent was negligible in cats receiving atracurium. We attribute the effect of the solvent to the Cremophor component. The mechanism of the interaction related to the cyclosporin is unknown. PMID- 2876722 TI - Pharmacodynamic profile of bisoprolol, a new beta 1-selective adrenoceptor antagonist. AB - The pharmacodynamic profile of bisoprolol, a new beta 1-selective adrenoceptor antagonist, was investigated in four independent studies including 36 healthy male volunteers. Using the model of exercise-induced tachycardia (ET) the beta adrenoceptor blocking properties of bisoprolol (2.5-40 mg) were examined in comparison to metoprolol (50 and 100 mg), propranolol (40 and 80 mg) and atenolol (50 and 100 mg). The maximal reduction of ET was achieved between 1 and 4 h following single oral administration. The dose-response relationship using individual maximal reduction of ET showed, on a molar basis, that bisoprolol is about 5, 7 and 10 times more effective than propranolol, atenolol and metoprolol, respectively. In the model of insulin-induced hypoglycaemia bisoprolol behaved as a beta 1-selective adrenoceptor antagonist. There was a good correlation (r = 0.94) between the log bisoprolol concentration and the reduction in exercise induced tachycardia. Bisoprolol is a potent new cardioselective beta-adrenoceptor antagonist with a competitive action at beta 1-adrenoceptors. PMID- 2876723 TI - Comparison of levocabastine, a new selective H1-receptor antagonist, and disodium cromoglycate, in a nasal provocation test with allergen. AB - The effect of intranasal administration of levocabastine, a new selective H1 receptor antagonist, was investigated in a nasal provocation test (NPT) performed with allergens. The NPT allowed a quantitative estimation of the nasal allergic threshold (concentration of allergen necessary to trigger the reaction). In addition, the intensity of the three major rhinitis symptoms (obstruction, rhinorrhea and sneezing) was determined. Twelve adult patients, allergic to grass pollen, underwent a first NPT without pretreatment ('initial NPT'); the NPT was then repeated after the single intranasal administration of either placebo, 8 mg disodium cromoglycate (DSCG) or 0.2 mg levocabastine in a double-blind random order. The NPTs gave reproducible results since both the threshold and symptom intensities were similar in the initial NPT and in the NPT performed after placebo. The reaction threshold increased in 8/12 patients after DSCG (0.05 less than P less than 0.1) and in 9/12 patients after levocabastine (P less than 0.05). Levocabastine clearly inhibited rhinorrhea (P less than 0.001) and sneezing (P less than 0.02) but did not influence the nasal obstruction. DSCG inhibited rhinorrhea only (P less than 0.01). The intranasal administration of levocabastine might be useful in the treatment of allergic rhinitis. PMID- 2876724 TI - The antisecretory effects of zaltidine, a novel long-acting H2-receptor antagonist, in healthy volunteers and in subjects with a past history of duodenal ulcer. AB - The potency and duration of the antisecretory action of zaltidine, a novel H2 receptor antagonist, have been examined in healthy volunteers and in patients with previous duodenal ulceration. In eight healthy male volunteers single oral doses of 5 mg, 25 mg and 100 mg produced dose-related inhibition of basal and pentagastrin-stimulated acid output (M.A.O.) with an estimated ID50 of 40 mg for the latter. In eight subjects with duodenal ulceration single 100 mg and 200 mg doses produced 85% and 97% inhibition of M.A.O. at peak (3 h post-dose) and 20% and 23% inhibition at 24 h, respectively; inhibition of basal acid output was 97% at 3 h and 50% at 24 h with both doses. The long duration of action of zaltidine is ascribed to its relatively slow elimination from the plasma. PMID- 2876725 TI - lac permease of Escherichia coli: histidine-322 and glutamic acid-325 may be components of a charge-relay system. AB - When Glu-325 in the lac permease of Escherichia coli is replaced with Ala, lactose/H+ symport is abolished. Thus, the altered permease catalyzes neither uphill lactose accumulation nor efflux. Remarkably, however, permease with Ala 325 catalyzes exchange and counterflow at completely normal rates. Taken together with the results presented in the accompanying paper [Puttner, I. B., Sarkar, H. K., Poonian, M. S., & Kaback, H. R. (1986) Biochemistry (preceding paper in this issue)], the findings suggest that the His-322 and Glu-325 may be components of a charge-relay system that plays an important role in the coupled translocation of lactose and H+. PMID- 2876726 TI - Characterization of native and reconstituted hydrogen ion pumping adenosinetriphosphatase of chromaffin granules. AB - The ATP-dependent H+ pump from adrenal chromaffin granules is, like the platelet dense granule H+ pump, essentially insensitive to the mitochondrial ATPase inhibitors sodium azide, efrapeptin, and oligomycin and also insensitive to vanadate and ouabain, agents that inhibit the Na+,K+-ATPase. The chromaffin granule H+ pump is, however, sensitive to low concentrations of NEM (N ethylmaleimide) and Nbd-Cl (7-chloro-4-nitro-2,1,3-benzoxadiazole). These transport ATPases may thus belong to a new class of ATP-dependent ion pumps distinct from F1F0-and phosphoenzyme-type ATPases. Comparisons of ATP hydrolysis with ATP-dependent serotonin transport suggest that approximately 80% of the ATPase activity in purified chromaffin granule membranes is coupled to H+ pumping. Most of the remaining ATPase activity is due to contaminating mitochondrial ATPase and Na+,K+-ATPase. When extracted with cholate and octyl glucoside, the H+ pump is solubilized in a monodisperse form that retains NEM sensitive ATPase activity. When reconstituted into proteoliposomes with crude brain phospholipid, the extracted enzyme recovers ATP-dependent H+ pumping, which shows the same inhibitor sensitivity and nucleotide dependence as the native pump. These data demonstrate that the predominant ATP hydrolase of chromaffin granule membrane is also responsible for ATP-driven amine transport and granule acidification in both native and reconstituted membranes. PMID- 2876728 TI - Membrane potential dependency of glutamic acid transport in rabbit jejunal brush border membrane vesicles: K+ and H+ effects. AB - We have applied our recently developed approach for quantitative generation and estimation of membrane potential differences (Berteloot, A. (1986) Biochim. Biophys. Acta 857, 180-188) to the reevaluation of glutamic acid transport rheogenicity in rabbit jejunal brush-border membrane vesicles. Membrane diffusion potentials were created by altering iodide concentrations in the intra- and extravesicular compartments while keeping isosmolarity, isotonicity and ionic strength constant by chloride replacement. The known value of ion permeabilities relative to sodium in this preparation also allows calculation of membrane potential differences using the Goldman-Hodgkin-Katz equation. This strategy appears superior to more classical methods involving ionophore-induced membrane diffusion-potentials of protons or potassium as both cations have been shown to participate in the transport mechanism. In this paper, we demonstrate that this approach is perfectly suitable for the investigation of membrane potential dependency of glutamic acid transport as our results showed that chloride replacement by iodide did not affect uptake in vesicles with membrane potential clamped to zero by gramicidin D (sodium conditions) or by gramicidin D plus valimonycin (sodium + potassium conditions). The method thus allows to dissociate membrane potential effects from possible effects that might be introduced by altering the anion species. In these conditions, our studies clearly demonstrate that glutamic acid uptake, whether analyzed over a 1 min time scale or under initial rate conditions, was sensitive to membrane potential differences. However, our results also show that the electrogenicity of the transport system varied depending upon the intravesicular presence or absence of potassium, its presence stimulating the membrane potential dependency of uptake. This effect is modulated by the internal pH and it is concluded that inside H+ and K+ are not equivalent as countertransported cations. The external pH also seems to modulate the response to potential by acting on the fully loaded form(s) of the transporter. The possibility that outside H+ competes for (an) external Na+ binding site(s) and/or precludes the attachment of (an) extra sodium ion(s) should be considered. PMID- 2876727 TI - Efficient reconstitution of mitochondrial energy-transfer reactions from depleted membranes and F1-ATPase as a function of the amount of bound oligomycin sensitivity-conferring protein (OSCP). AB - Pig heart mitochondrial membranes depleted of F1 and OSCP by various treatments were analyzed for their content in alpha and beta subunits of F1 and in OSCP using monoclonal antibodies. Membrane treatments and conditions of rebinding of F1 and OSCP were optimized to reconstitute efficient NADH- and ATP-dependent proton fluxes, ATP synthesis and oligomycin-sensitive ATPase activity. F1 and OSCP can be rebound independently to depleted membranes but to avoid unspecific binding of F1 to depleted membranes (ASUA) which is not efficient for ATP synthesis, F1 must be rebound before the addition of OSCP. The rebinding of OSCP to depleted membranes reconstituted with F1 inhibits the ATPase activity of rebound F1, while it restores the ATP-driven proton flux measured by the quenching of ACMA fluorescence. The rebinding of OSCP also renders the ATPase activity of bound F1 sensitive to uncouplers. The rebinding of OSCP alone or F1 alone, does not modify the NADH-dependent proton flux, while the rebinding of both F1 and OSCP controls this flux, inducing an inhibition of the rate of NADH oxidation. Similarly, oligomycin, which seals the F0 channel even in the absence of F1 and OSCP, inhibits the rate of NADH oxidation. OSCP is required to adjust the fitting of F1 to F0 for a correct channelling of protons efficient for ATP synthesis. All reconstituted energy-transfer reactions reach their optimal value for the same amount of OSCP. This amount is consistent with a stoichiometry of two OSCP per F1 in the F0-F1 complex. PMID- 2876729 TI - Differential changes of nuclear-envelope-associated enzyme activities involved in nucleocytoplasmic mRNA transport in the developing rat brain and liver. AB - Nucleocytoplasmic transport of rat liver mRNA is thought to be regulated by a nucleoside triphosphatase whose activity in the intact nuclear envelope is stimulated by the 3'poly(A) tail of poly(A)+ mRNA. In contrast to the liver mRNA, the mRNA from rat brain contains a great population of poly(A)- mRNA's that does not appear until after birth. Measurements of the nuclear-envelope-associated enzyme activities involved in mRNA transport, and their dependence on endogenous (isolated cytoplasmic mRNA-transport-stimulating proteins) and exogenous (poly(A), lectins, and neoglycoproteins) factors during prenatal and postnatal rat brain and liver development, revealed marked organ-dependent differences paralleling the appearance of the poly(A)- mRNA unique in the brain. PMID- 2876730 TI - The simultaneous hydrolysis of glutathione and glutamine by rat kidney gamma glutamyltransferase. AB - The simultaneous hydrolysis of L-glutamine and glutathione by rat kidney gamma glutamyltransferase has been studied. At concentrations of the two substrates giving rates approximating to Vmax, it is shown that glutamine hydrolysis predominates. Under saturating conditions for both substrates, 65% of the glutamic acid produced is derived from glutamine. Using [14C]glutamine it is also shown that at physiological plasma concentrations of glutamine (in excess of 400 microM) and glutathione (20 microM) glutamine hydrolysis is the predominating reaction. We therefore suggest that both glutamine and glutathione are important in vivo donors for gamma-glutamyltransferase. PMID- 2876731 TI - Lipid peroxidation and cytotoxicity of Ehrlich ascites tumor cells by ferric nitrilotriacetate. AB - Ferric nitrilotriacetate, which causes in vivo organ injury, induced lipid peroxidation and cell death in Ehrlich ascites tumor cells in vitro. The process was inhibited by butylated hydroxyanisole and enhanced by vitamin C and linolenic acid, indicating a close relationship between cytotoxicity and the lipid peroxidizing ability of Fe3+ NTA. The cytotoxicity was suppressed by glucose and a temperature below 20 degrees C. Lipid peroxidation of Fe3+ NTA-treated cells was greater at 0 degree C than at 37 degrees C, contrary to results with Fe3+ NTA treated plasma membranes of Ehrlich ascites tumor cell. These results suggested that metabolism and membrane fluidity are important factors in the expression of the Fe3+ NTA-induced cytotoxicity. H2O2 showed a lower cytotoxicity than did Fe3+ NTA but a greater lipid peroxidizing ability. H2O2 appeared to damage the cells less, and was quenched rapidly by cellular metabolism unlike Fe3+ NTA. In transferrin-free medium, Ehrlich ascites tumor cell readily incorporated Fe3+ NTA, and iron uptake was greater than NTA-uptake in Fe3+ NTA-treated cells, suggesting that Ehrlich ascites tumor cell incorporated iron from Fe3+NTA and metabolized it into an inert form such as ferritin. PMID- 2876732 TI - Gamma glutamyl transpeptidase in the vasculature of the rat testis. AB - Activity of gamma glutamyl transpeptidase (GGT) in the testes of mature and prepuberal rats was investigated histochemically and biochemically. Histochemically, the enzyme activity was localized predominantly in the arterial and arteriolar endothelium and was absent from the capillaries and the seminiferous tubules. The activity in the arterial endothelium extended to the testicular artery on the surface of the testis and in the spermatic cord, but the veins in both the pampiniform plexus and on the testicular surface were negative. The endothelium of the testicular artery was already faintly positive at birth, and the activity increased during the second and third postnatal week during the branching and remodeling of the intratesticular arteries and arterioles. Activity of GGT was estimated quantitatively after dissection of the testis into tubular and interstitial tissue. The enzyme activity was very low in the tubules. It was fivefold stronger in the interstitium, and this activity was further enhanced by pretreatment of the dissected tissue with collagenase to remove the Leydig cells. PMID- 2876733 TI - Protein kinase activities in rat liver nuclei: effects of age and partial hepatectomy. AB - Selective substrates and inhibitors have been used to measure kinases phosphorylating endogenous proteins in rat liver nuclei during growth and regeneration after partial hepatectomy. Peaks in activity were found at 5, 22, and 29 hours after partial hepatectomy. Administration of alpha 1 and beta adrenergic blockers suggested that the Be2+ sensitive and cyclic AMP-dependent protein kinases were interdependently regulated by Ca2+ and cyclic AMP. PMID- 2876734 TI - [Role of calmodulin in the contractile function of the myocardium]. AB - The effect of phenothiazines-trifluoroperazine frenolone, majeptile and aminazine on contractility of papillar muscle of Wistar male rats associated with short term Ca-concentration increase up to 4 mM has been studied. There has been found the parameter-relaxation index-the change of which under the effect of phenothiazines (10(-5) M in all the cases) made use of significantly correlates with the constants, which reflect the similarity of given agents with calmodulin. PMID- 2876735 TI - [Tyrosine inhibition of anaphylactic shock in guinea pigs]. AB - Experimental investigations on guinea-pigs were carried out to study the role of tyrosine in the prevention of anaphylaxis. It should be noted that the intensity of clinical manifestations of anaphylactic shock was reduced in 5 out of 24 L tyrosine fed guinea-pigs (20.83%), while in 9 animals (37.5%) anaphylactic shock did not develop. 100% death of control animals was registered. The effect of tyrosine was absent only in 10 guinea-pigs. Positive effect of tyrosine was followed by tyrosine-aminotransferase activation with a tendency towards the decrease in tyrosine plasma level and the rise in cortisol blood level. It is suggested that tyrosine increases glucocorticoid secretion of the adrenal cortex: Glucocorticoids in their turn, enhance tyrosine-aminotransferase activity in the animal liver. PMID- 2876736 TI - [Effect of adrenoblockers on the analgesic effect of GABA-positive preparations]. AB - The experiments on rats have shown that selective alpha 1 and alpha 2 adrenoceptor blockers (prazosin and yohimbine) and an inhibitor of dopamine-beta hydrolase FD-008 failed to change the antinociceptive effect of baclofen, a direct GABAB receptor agonist. The antinociceptive effect of THIP and depakin, acting predominantly on GABAA receptors, was significantly reduced by prazosin, FD-008 and yohimbine in vocalization test. In tail-flick test the analgetic effect of THIP and depakin was not altered by prazosin and FD-008, but was increased by yohimbine. The role of adrenergic mechanisms in GABAA and GABAB receptor-mediated analgesia is discussed. PMID- 2876737 TI - [Migration of T-lymphocyte precursors into the thymus and the factors affecting this process]. AB - Migration of FITC-labeled mouse bone marrow cells into the thymus was measured by flow cytometric analysis 3 hours after intravenous injection of cells into irradiated mice. The percentage of cells reaching the thymus diminished when the dose of injected cells increased. The dependence of the number or labeled cells in the thymus on the dose of injected cells was not linear. Pretreatment of cells with anti-SC-I serum, peanut lectin or H-2 incompatibility antigen abolished thymus migration, while treatment with anti-Thy-I serum, soybean lectin, trypsin or Thy-I-incompatibility antigen diminished cellular migration and treatment with neuraminidase enhanced it. It was concluded that the main type of migrating cells is SC-1+ precursors of T-lymphocytes. Penetration of these cells through the blood-thymus barrier is based on the recognition of their partly sialized surface glycoprotein receptors by membrane lectins of the blood-thymus barrier cells. PMID- 2876738 TI - A novel basis for delta beta-thalassemia in a Chinese family. AB - We have studied a Chinese family in which beta-thalassemia and delta beta thalassemia were found in simple and compound heterozygous states. The delta beta thalassemia heterozygote (the mother) had 22.3% hemoglobin F, of which 40% was G gamma and 60% A gamma; globin chain studies showed an alpha/beta + gamma ratio of 1.36. The compound heterozygote for delta beta-thalassemia and beta-thalassemia (the child) had the clinical picture of thalassemia intermedia and an alpha/beta + gamma ratio of 4.44. Gene mapping studies were performed using DNA from the affected child. Seventy kilobases of DNA in the beta-globin gene cluster starting upstream from the epsilon-globin gene and ending downstream from the beta-globin gene were mapped, and no detectable deletions or rearrangements were detected. In addition, heterozygosity was detected at multiple polymorphic restriction sites in and 3' to the beta-globin gene, which excludes the possibility of a deletion of the entire beta-globin gene cluster. This is the first example of a nondeletion delta beta-thalassemia associated with increased expression of both G gamma and A gamma genes. PMID- 2876739 TI - Somatostatin in cerebrospinal fluid. PMID- 2876740 TI - Treatment of essential hypertension. AB - While no consensus over the treatment of essential hypertension has been reached, three recent major trials offer guidance to the clinician. The results of these trials and the role of new and old drugs in the treatment of hypertension are discussed. PMID- 2876741 TI - Somatostatin in the treatment of severe upper gastrointestinal bleeding: a multicentre controlled trial. AB - To evaluate the effectiveness of somatostatin versus combined cimetidine and pirenzepine in the treatment of upper gastrointestinal (GI) bleeding of peptic origin, a multicentre controlled, prospective, randomized and double blind trial has been undertaken in 60 subjects. Strict selection criteria were followed. All subjects were diagnosed by endoscopy during the first 18 h after admission. Endoscopic stigmata of recent haemorrhage were also evaluated. Sixty-five per cent of the subjects presented with severe upper GI bleeding (blood pressure less than or equal to 100 mmHg, pulse rate greater than or equal to 110, haematocrit less than or equal to 30 per cent), and in 71.6 per cent stigmata were found. Thirty patients (Group 1) received a somatostatin infusion (250 micrograms/h continuously during 120 h) and 30 patients (Group 2) received cimetidine (200 mg IV every 4 h for 5 days) and pirenzepine (10 mg IV every 8 h for 5 days). Both groups were homogeneous for sex, age, backgrounds, bleeding source, grade of bleeding (moderate or severe) and presence or not of stigmata. Bleeding stopped in 27 subjects of Group 1 (90 per cent and in 20 subjects of Group 2 (66.67 per cent) (P less than 0.05, chi 2 test). The time until the bleeding stopped was significantly shorter in patients of group 1 (3.44 +/- 0.53 h) than in patients of group 2 (8.12 +/- 1.94 h) (P less than 0.05, Mann-Whitney U test). The number of blood units required for Group 1 (2.26 +/- 0.35) was significantly lower than the one required for Group 2 (3.90 +/- 0.51) (P less than 0.005, Wilcoxon test). Significant differences were not observed between the two groups regarding cross over subjects, re-bleeding, surgery (P = 0.0635, Fisher's exact test) and hospital stay. The mortality of the trial was 5 per cent. There was no toxicity during somatostatin, cimetidine or pirenzepine infusion. In conclusion, somatostatin was more effective than cimetidine plus pirenzepine in the control of severe upper GI bleeding of peptic origin, with a lower interval time to stop bleeding and reduced transfusion requirements. PMID- 2876743 TI - Boys with late descending testes: the source of patients with "retractile" testes undergoing orchidopexy? PMID- 2876742 TI - Isolating the gene for Duchenne muscular dystrophy. PMID- 2876744 TI - Sulphasalazine in ankylosing spondylitis: a double blind controlled study in 60 patients. AB - Sulphasalazine has been reported to be effective in ankylosing spondylitis with peripheral arthritis, but its efficacy in spondylitis is unknown. Thus 60 patients with active ankylosing spondylitis without peripheral arthritis or gastrointestinal symptoms were randomly allocated to one of two therapeutic groups. One group received 2 g sulphasalazine daily for six months and the other a placebo. Thirteen patients (six given placebo and seven given sulphasalazine) dropped out of the trial and were considered to be treatment failures. After six months' follow up efficacy was rated as good or very good by 15 of the 30 patients given sulphasalazine and by only six of the 30 given placebo (p less than 0.02). Furthermore, in the patients given sulphasalazine the daily consumption of non-steroidal anti-inflammatory drugs, functional index, and plasma IgG concentrations had fallen significantly. These data suggest that sulphasalazine may be a safe and effective treatment for spondylitis in ankylosing spondylitis. PMID- 2876746 TI - A practical guide to prescribing hypnotic benzodiazepines. PMID- 2876745 TI - Course of blood pressure in mild hypertensives after withdrawal of long term antihypertensive treatment. Medical Research Council Working Party on Mild Hypertension. AB - A series of 1418 men and 1,347 women with mild hypertension (diastolic phase V 90 109 mm Hg) aged 35-64 who had either had long term antihypertensive treatment with bendrofluazide or propranolol or taken placebo tablets for a similar period were randomly allocated to groups in which their tablets were either stopped or continued. The course of blood pressure and of biochemical variables was followed up for two years. Mean blood pressures rose rapidly after the withdrawal of active treatment, and between nine months and one year after stopping treatment the antihypertensive effect had almost disappeared. The effect persisting longer than this, and possibly due to resetting of the baroreceptors or of other blood pressure control mechanisms, was very small, and as the rise in mean pressure was due to an upward movement in general distribution there was no evidence of a subgroup in whom these mechanisms had been permanently reset to a clinically important extent. After withdrawal of propranolol the rise in pressure was more rapid in younger than in older people. After stopping bendrofluazide pressure rose more rapidly in men who had had higher pressures before and during treatment; this effect was not seen in women. Disturbances in biochemical variables associated with drug treatment had largely resolved by the end of two years after withdrawal. Stopping placebo tablets made no consistent difference to blood pressure. PMID- 2876747 TI - Confusion after admission to hospital in elderly patients using benzodiazepines. PMID- 2876748 TI - Influence of intrinsic sympathomimetic activity on respiratory function. PMID- 2876749 TI - CPP, a new potent and selective NMDA antagonist. Depression of central neuron responses, affinity for [3H]D-AP5 binding sites on brain membranes and anticonvulsant activity. AB - Properties of a new potent antagonist acting selectively at N-methyl-D-aspartate (NMDA) type excitatory amino acid receptors are described. This compound, 3-((+/ )-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) is more potent than all previously reported NMDA antagonists in depressing mammalian spinal neuronal responses (cat and immature rat), in its affinity for [3H]D-AP5 (a radiolabelled NMDA antagonist) binding sites on rat brain membranes, and as an anticonvulsant in mice. PMID- 2876751 TI - GABAergic and catecholaminergic synaptic interactions in the macaque hypothalamus: double label immunostaining with peroxidase-antiperoxidase and colloidal gold. AB - Immunogold staining (IGS) for glutamic acid decarboxylase (GAD) was combined with the peroxidase-antiperoxidase (PAP) technique for tyrosine hydroxylase (TH) to analyze gamma-aminobutyric acid-catecholaminergic neuronal interactions in the rhesus hypothalamus. At the light-microscopic level, TH-immunoreactive (-IR) perikarya and their fibers (brown) were observed in the anterior ventral periventricular area (AVPV), the arcuate nucleus (ARC) and the adjacent periventricular zone (ARC-PVZ). GAD-IR processes (light red) were also present throughout the hypothalamus and appeared to contact some TH-IR neurons. At the electron-microscopic level, PAP was present in perikarya, dendrites, axons and axon terminals of TH-IR neurons. Colloidal gold particles (15 nm) were found only in dendrites and axon terminals of GAD-IR neurons. Labeled GAD terminals typically contained small, clear synaptic vesicles, while TH terminals contained these and sometimes one or two dense-core vesicles. In the ARC and ARC-PVZ, asymmetrical (Gray I) axodendritic synapses occurred between GAD and TH-IR profiles, with TH/GAD directionality more prevalent. Symmetrical (Gray II) synapses were less common, with either TH or GAD presynaptic in axodendritic and dendrodendritic contacts. GAD/GAD interactions were not observed, but TH/TH contacts appeared to be mostly dendrodendritic. In the AVPV, only symmetrical synapses were encountered, and their directionality was difficult to determine. GAD- and TH-IR dendrites frequently established dendrodendritic synapses, but GAD/TH dendrosomatic synapses were seldom seen. These results illustrate the complex interactions of GAD- and TH-containing elements in the neuroendocrine hypothalamus. PMID- 2876750 TI - Action of 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP): a new and highly potent antagonist of N-methyl-D-aspartate receptors in the hippocampus. AB - A new compound, 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), has been evaluated as an excitatory amino acid receptor antagonist using electrophysiological assays and radioligand binding. In autoradiographic preparations, CPP reduces L-[3H]glutamate binding in regions of the hippocampus rich in N-methyl-D-aspartate (NMDA) receptors, but not in regions rich in kainate sites. In isolated membrane fraction preparations, CPP displaces L-[3H]glutamate binding to NMDA sites, but does not compete with the binding of selective kainate or quisqualate site ligands. CPP potently reduces depolarizations produced by application of NMDA but not depolarizations produced by quisqualate or kainate. Its order of potency against excitatory amino acid-induced responses in the hippocampus is NMDA greater than homocysteate greater than aspartate greater than glutamate greater than kainate greater than or equal to quisqualate. CPP has no effect on lateral perforant path responses or on inhibition of these responses by 2-amino-4-phosphonobutyrate. Finally, at doses that do not affect Schaffer collateral synaptic transmission, CPP reversibly blocks the induction of long term potentiation of Schaffer synaptic responses. This new compound is, therefore, a highly selective brain NMDA receptor blocker, and the most potent such by nearly an order of magnitude. PMID- 2876752 TI - Effects of kainic acid and other excitotoxins in the rat superior colliculus: relations to glutamatergic afferents. AB - In this study we have performed surgical, chemical and combined surgical/chemical lesions in order to elucidate neurotransmitter mechanisms in the superior colliculus (SC) of albino rats. Visual cortex (VC) ablation reduced high affinity (HA) uptake of D-Asp by 32% in the deafferented SC. Local injection of kainic acid (KA) into SC reduced HA D-Asp uptake selectively in the lower dose range (less than 1 nmol) by 50-60%. The GABAergic marker glutamate decarboxylase (GAD) was decreased by maximally 60% only at doses exceeding 2 nmol. Choline acetyltransferase (ChAT), however, was not affected at any of the doses administered. VC ablation provided an almost complete protection against 1 nmol KA. When KA was injected 2 days prior to VC ablation an additive effect on HA D Asp uptake of the two lesions was observed. From these observations we infer that the notion of a glutamatergic projection from VC to SC has been strengthened. Moreover, local neurons in intermediate layers account for about 60% of the HA D Asp uptake in SC, and these are most likely impinged upon by the glutamatergic afferents. The neurotoxic effects of KA were compared with those of some suspected endogenous excitotoxins, i.e. N-methyl tetrahydrofolic acid (Me-THF), other folates and the tryptophan metabolite quinolinic acid (QA). N-methyl tetrahydrofolic acid, Me-THF (4 and 10 nmol) reduced HA D-Asp uptake by about 50%, only when coinjected with ascorbic acid. GAD and ChAT were not affected at either of the doses. QA was about 100-fold less potent than KA on a molar basis, and the maximal reduction of GAD was similar in QA and KA injected animals, whereas the maximal reduction of HA D-Asp was only 40% after QA injection in SC. We conclude that Me-THF, QA and KA exert their neurotoxic actions by different mechanisms as judged by the behavioral, histopathological and biochemical sequelae seen after local injections of the respective substances in intermediate layers of SC and corroborate data obtained from other brain areas. PMID- 2876753 TI - Gonadal hormone regulation of neurotransmitter synthesizing enzymes in the developing hypogastric ganglion. AB - The effects of postnatal castration at 10-11 days of age were examined in the sympathetic hypogastric ganglion (HG). Assays for choline acetyltransferase (ChAT) activity, a biochemical marker for presynaptic cholinergic maturation, and the activity of tyrosine hydroxylase (T-OH), the rate limiting enzyme in postsynaptic catecholamine biosynthesis and an index of noradrenergic development, were employed to monitor HG ontogeny. After 1 postoperative week ChAT activity and T-OH activity were significantly reduced in castrated animals as compared to sham operated controls. Over the 12 week postoperative observation period T-OH activity never varied significantly from the day 10 precastration value; thus, by 12 postoperative weeks T-OH activity in the castrated animals was 3% of the control value. In contrast, ChAT activity and total ganglion protein continued to mature in the castrated animals, but at diminished rates, so that by 12 postoperative weeks both indices were approximately 40% of the control values. Testosterone replacement therapy restored both ChAT and T-OH activities to control levels. Additionally, testosterone replacement restored the control level of activity for DOPA decarboxylase, a catecholamine synthetic enzyme which is differentially regulated from T-OH. The failure of enzyme activities to develop normally subsequent to castration on postnatal day 10 suggests that testosterone regulates the postorganizational maturation of postsynaptic noradrenergic enzyme activities and presynaptic ChAT activity. PMID- 2876754 TI - Localization of [3H]glutamate binding sites in rat adrenal medulla. AB - A significant activity of L-[3H]glutamic acid binding was detected in the membranous particulate preparations obtained from the rat adrenal glands. In vitro addition of sodium acetate (100 mM) resulted in a drastic enhancement of the binding to cerebral preparations, while inducing a significant inhibition of the adrenal binding. Quisqualic acid elicited a prominent suppression of the adrenal binding in a concentration-dependent manner to a slightly greater extent than the inhibition of cerebral binding. N-Methyl-D-aspartic acid exerted a significant stimulatory action on the adrenal binding without affecting the cerebral binding. The adrenal medullary part possessed more than 5-fold higher binding activity than that in cortical part. These results suggest the possible existence of [3H]glutamate binding sites in rat adrenal glands which are distinctly different from those in the central structures. PMID- 2876755 TI - Expression and regulation of tyrosine hydroxylase in adult sensory neurons in culture: effects of elevated potassium and nerve growth factor. AB - To determine whether similar molecular mechanisms regulate the same proteins in diverse neuronal populations, the present study compared regulation of tyrosine hydroxylase (TOH) in placodal sensory and neural crest-derived sympathetic neurons in tissue culture. Long-term explant cultures of adult nodose and petrosal sensory ganglia (NPG) contained abundant TOH-immunoreactive neurons and exhibited TOH catalytic activity, as in vivo. After an initial decline during the first week of culture, enzyme activity was maintained at a stable plateau of 60% of zero time values for at least 3 weeks. However, exposure of 2-week-old cultures to depolarizing concentrations of potassium (K+; 40 mM) increased TOH activity approximately two-fold; total protein was unchanged, suggesting that the rise was due to increased TOH specific activity. Therefore, membrane depolarization in vitro appears to regulate this specific catecholaminergic (CA) trait in sensory, as in sympathetic CA cells. In sympathetic neurons, NGF regulates TOH activity throughout life. In marked contrast, TOH activity in adult NPG cultures was unchanged in the presence of 0, 10 or 100 units NGF/ml or in the presence of high concentrations of antiserum against the beta-subunit of NGF. Adult sympathetic neurons, however, grown under identical conditions, exhibited a 5- to 10-fold rise in TOH activity in the presence of NGF. Thus, unlike sympathetics, CA metabolism in adult NPG neurons is not regulated by NGF in vitro; NGF is therefore unlikely to mediate target effects on CA metabolism in placodal sensory neurons in vivo. Our findings indicate that certain mechanisms of CA regulation are shared by placodal sensory and neural crest-derived sympathetic neurons, whereas others are not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876756 TI - Perinatal dietary supplementation with a soy lecithin preparation: effects on development of central catecholaminergic neurotransmitter systems. AB - Previous work has shown that exposure of developing rats to soy lecithin preparations (SLP) influences macromolecular constituents of immature brain cells and causes abnormal behavioral patterns. To determine if synaptic mechanisms are adversely affected by SLP, we examined the developmental characteristics of noradrenergic and dopaminergic pathways in discrete brain regions. Although transmitter levels were unaffected, the utilization rates of both catecholamines were profoundly disturbed in an age-dependent, regionally-selective manner. Utilization tended to be subnormal in the preweanling stage, but demonstrated a postweaning elevation in cerebellum and midbrain + brainstem. Enhanced utilization persisted in the latter region only, and cerebral cortex actually showed a lowered utilization rate in adulthood (60 days of age). Transmitter uptake capabilities were also affected by developmental exposure to SLP, as was tyrosine hydroxylase activity. The patterns of effects on these two variables indicated that the altered transmitter utilization rate probably reflected a change in impulse activity in the affected neuron populations, with promotion of activity in the midbrain + brainstem and reduced activity in the cerebral cortex. These data indicate that dietary supplementation with SLP throughout perinatal development alters synaptic characteristics in a manner consistent with disturbances in neural function. PMID- 2876757 TI - Dissociation of locomotor impairment from mydriasis evoked by clonidine injected into cat's rostral hypothalamus. AB - The anterior hypothalamic preoptic area (AH/POA) was examined as a possible site of action of clonidine and other alpha noradrenergic receptor agonists which evoke motor and autonomic changes. Chronically indwelling guide cannulae were implanted stereotaxically in the diencephalon of the cat. Following post operative recovery, a micro-injection into AH/POA was made in a volume of 1.0 microliter of one of the following compounds: 5.0-50.0 micrograms clonidine, 5.0 50.0 micrograms norepinephrine, 5.0-50.0 micrograms phenylephrine and 5.0-50.0 micrograms methoxamine. The smallest dose of 5.0 micrograms clonidine produced a brief period of restlessness, licking, retching and emesis but a much longer lasting mydriasis. When the dose of clonidine was raised to 20 micrograms, the cat became behaviorally sedated, after a latency of about 15 min, for a period of up to 1.0-2.0 hr. This was accompanied by a prolonged period of mydriasis and preceded by a short interval of restlessness, licking, retching and emesis. After the highest dose of 50.0 micrograms clonidine was micro-injected in AH/POA, a profound impairment of motor activity, adynomia and restlessness developed within 15-20 min, persisted for 30 to 60 min and was accompanied also by mydriasis with maximal pupillary dilation lasting for up to six hr. When 5.0-50.0 micrograms phenylephrine or 5.0-50.0 micrograms norepinephrine were micro-injected at clonidine-reactive sites in AH/POA, only rarely were brief instances of restlessness, licking, retching and emesis observed; however, methoxamine at all doses tested failed to produce any visible signs of autonomic or motor disturbance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876758 TI - Effect of somatostatin on the vagal motor neuron in the rat. AB - Somatostatin-14 (SOM) effects on electrical properties of membrane in rat brainstem slice preparations were studied in vitro by intracellular recording. Vagal motoneurons in the nucleus dorsalis motoris nervi vagi (DMV) were hyperpolarized by SOM. SOM increased both negativity of membrane potential and input membrane conductance, and decreased synaptic noise. The effects persisted during synaptic blockade by tetrodotoxin (TTX) or [Ca]o-free-high-[Mg]o perfusion. The reversal potential of the hyperpolarization induced by SOM depended on [K]o concentration. Hill's coefficient calculated from the dose response curve was 2. The results suggest that SOM may inhibit visceral organ functions through the DMV. PMID- 2876760 TI - [Epidemiologic study of hemorrhagic fever with renal syndrome]. PMID- 2876759 TI - [Effect of delta-endotoxin of Bacillus thuringiensis israelensis on biochemical functional relationships in Diptera Aedes aegypti]. AB - A study of the action of very low doses of the delta-endotoxin of Bacillus thuringiensis israelensis on the larvae of Aedes aegypti (Diptera) gave evidence for peculiar properties of the dose/effect relations based on the variations of the regression slopes of functional relationships between the pairs cysteine/serine and fatty acids/histidine, by contrast with the pair fatty acids/glucose which exhibited a classical shaped relation. This indicates "crypto toxicological" processes, not lethal by themselves and without pathological symptoms, but able to initiate "pathogen-chaining" mechanisms leading, at the end, to a lethal secondary syndrome. PMID- 2876761 TI - [A preliminary study on the mechanism of changes of beta and M receptors in the lung tissue of guinea pigs with experimental allergic asthma]. PMID- 2876762 TI - [Measurement of oxidation-reduction potentials in the cultivation of Entamoeba histolytica]. PMID- 2876763 TI - Contribution of muscle relaxant to the haemodynamic course of high-dose fentanyl anaesthesia: a comparison of pancuronium, vecuronium and atracurium. AB - To define the role of muscle relaxants in haemodynamic responses to high-dose (75 micrograms X kg-1) fentanyl anaesthesia and to noxius stimuli associated with intubation and sternal spread during coronary artery bypass surgery, we compared haemodynamics between three groups of patients given either pancuronium (0.1 mg X kg-1, n = 11), vecuronium (0.086 mg X kg-1, n = 11) or atracurium (0.43 mg X kg 1, n = 12). Additional doses of the relaxants were given to maintain a 90 per cent neuromuscular block. Patients given pancuronium showed no increases in mean values of heart rate, arterial pressure or cardiac output during the induction of anaesthesia or after intubation, whereas a decrease in these variables was observed in the vecuronium group. The haemodynamics in the atracurium group were intermediate compared with the other two study groups. In spite of a decrease in coronary perfusion pressure, no patient given vecuronium developed myocardial ischaemia. An advantage of vecuronium over pancuronium and atracurium was an attenuation of the blood pressure response to sternotomy. Patients given atracurium had a small increase in pulmonary vascular resistance during sternotomy. Our patients continued their beta-adrenergic antagonist medication until the morning of the day of operation and they were pretreated with a small intravenous dose of diazepam (0.1 mg X kg-1) before induction of anaesthesia. These drugs may have prevented the deleterious haemodynamic effects observed by some investigators after the administration of pancuronium during high-dose fentanyl anaesthesia. PMID- 2876765 TI - Effects of para-substitution on tissue levels and alpha-adrenoceptor antagonist properties of tolazoline. AB - Tolazoline and a series of para-substituted analogues were examined in mice to determine the effects of para substitution on alpha-adrenoceptor antagonist potency and tissue disposition. alpha-Adrenoceptor antagonism was measured as abilities to attenuate the hypothermic or sedative actions of clonidine. In general, para substitution by electron-withdrawing metabolically stable groups (Cl, F) resulted in increased or unchanged brain levels of drug relative to tolazoline. The para substitution by electron-donating metabolically labile groups (CH3, OCH3) leads to reduced brain levels. Effects on alpha-adrenoceptor antagonist properties did not follow a similar pattern. Thus, increased or decreased antagonism of clonidine effects by para-chloro- or para-methyl tolazoline, respectively, could be attributed solely to increased or decreased brain levels of drug. para-Fluorotolazoline did not antagonize clonidine but was present in brain at levels equivalent to those of tolazoline. para Methoxytolazoline on the other hand could not be detected in any tissue but antagonised hypothermia more readily than sedation. These data indicate that the factors governing the disposition or alpha-adrenoceptor antagonist properties of tolazoline analogues are different and independent of each other. PMID- 2876764 TI - Treatment of stable angina pectoris with calcium antagonists alone or combined with beta-blocking agents: a review of the literature. AB - The calcium antagonists are presently accepted as the treatment of choice for vasospastic angina. They are accepted by some as a good second choice therapy in the treatment of stable angina pectoris, while by others as an excellent first choice in its treatment. When introduced to the North American market, warning was given of the risk of left ventricular failure and/or atrioventricular block from their combination with beta-blockers. Perhaps now a deeper knowledge of their hemodynamic and electrophysiologic properties allows us to conceptualize potent and safe anti-anginal associations by use, in specific patients, of differing combinations. Thus we must learn to use with care and flair this new form of treatment which offers our severely afflicted patients much greater symptomatic relief. PMID- 2876766 TI - Postsynaptic alpha-adrenoceptor characterization and Ca2+ channel antagonist and activator actions in rat tail arteries from normotensive and hypertensive animals. AB - Postsynaptic alpha-adrenoceptors in the rat tail artery have been examined by determining the pA2 values for antagonists against several alpha-adrenoceptor agonists. In this tissue the alpha-adrenoceptor agonists all produce concentration-dependent mechanical responses with the following rank order of potency: clonidine greater than norepinephrine greater than phenylephrine greater than UK 14304 greater than B-HT 920. Antagonism by prazosin and yohimbine of phenylephrine, norepinephrine, and clonidine responses does not reveal the anticipated discrimination between alpha 1- and alpha 2-adrenoceptors. Thus, pA2 values for prazosin (9.1-9.5), yohimbine (7.2-7.4), and corynanthine (7.0-7.1) and idazoxan (7.6) do not show large differences between these receptor agonists and suggests the predominance of alpha 1-adrenoceptor mediated contractile responses in this preparation. Significant differences between antagonist activities (pA2 values) in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) artery preparations have not been observed. The sensitivity sequence of alpha-adrenoceptor agonist-induced responses to nifedipine and D 600 is B-HT 920 greater than clonidine greater than phenylephrine greater than norepinephrine. Dependence of agonist response upon extracellular Ca2+ parallels the sensitivity to Ca2+ channel antagonists. Sensitivity to D 600 of phenylephrine responses increased with decreasing concentration of phenylephrine or with receptor blockade by phenoxybenzamine: sensitivity of responses to B-HT 920 was not affected by these procedures. Tail artery strips from WKY and SHR do not exhibit major differences in sensitivity to D 600 or to Ca2+ depletion. Bay k 8644, a Ca2+ channel activator, produces concentration-dependent mechanical responses in the tail artery in the presence of modestly elevated K+ concentrations (10-15 mM): these actions of elevated K+ can be mimicked by both alpha 1- and alpha 2 adrenoceptor agonists including methoxamine, St 587, UK 14304, and clonidine. These studies do not provide clear evidence for the existence of discrete postsynaptic alpha 1- and alpha 2-adrenoceptor populations in rat tail artery as indicated by pA2 values or Ca2+ dependence of response. PMID- 2876767 TI - Amiloride acts as an alpha-adrenergic antagonist in the isolated rat tail artery. AB - In the final concentration of 100 microM, amiloride increased substantially the overflow of endogenous noradrenaline and decreased that of 3,4 dihydroxyphenylethylene glycol from the rat tail artery into Krebs solution supplemented with 10 microM veratridine. The overflow of the amine into a 120 mM K version of Krebs solution was unaffected by amiloride, while that of the glycol was reduced. Abolition of the contractile response to 10 microM veratridine by 2 microM phentolamine indicated that the response was due to release of endogenous noradrenaline. Addition of amiloride in the final concentrations of 10 and 100 microM caused relaxation of strips contracted by the alkaloid. The dose-response relations for exogenous noradrenaline measured in the absence or presence of 50 microM amiloride indicated that the drug acted as a reversible competitive alpha adrenergic antagonist. The phentolamine-resistant component of the contractile response to the 120 mM-K solution was unaffected by 100 microM amiloride. Although the exact site of action of amiloride remains to be determined, it can be concluded that amiloride inhibits adrenergic transmission at a postsynaptic site at a step preceding elevation of myoplasmic Ca2+. PMID- 2876768 TI - Oosporogenesis by Lagenidium giganteum: induction and maturation are regulated by calcium and calmodulin. AB - Induction and maturation of the sexual stage (oospores) of the facultative mosquito parasite Lagenidium giganteum (Oomycetes: Lagenidiales) are complex developmental processes regulated by calcium-dependent events. Use of developmentally synchronized cultures of L. giganteum allowed stage-specific disruption of calcium metabolism. A calcium chelator (EGTA), an ionophore (chlortetracycline), and inhibitors of the calcium-binding protein calmodulin (dibucaine, trifluoperazine, chlorpromazine) disrupted several discrete developmental steps associated with oosporogenesis: induction of antheridia, gametangial fusion, meiosis, oospore wall formation, and subsequent spore maturation. Extracellular calcium is necessary for oosporogenesis to proceed normally and under some conditions magnesium has a synergistic effect with calcium on oospore induction. Results are discussed in relation to calcium mediation of fusion events in a number of model membrane and biological systems. PMID- 2876771 TI - Synthesis of disaccharide analogues of methyl 4-O-alpha-D-galactopyranosyl-beta-D galactopyranoside ("methyl urobioside"), the minimum structure recognized by p fimbriated E. coli. PMID- 2876770 TI - Immunostimulation with intrapleural BCG as adjuvant therapy in resected non-small cell lung cancer. The Ludwig Lung Cancer Study Group (LLCSG). AB - A prospective randomized trial was performed to evaluate the role of adjuvant local immunostimulation with bacillus Calmette-Guerin (BCG) in resected Stage I and Stage II non-small cell bronchogenic carcinoma. The patients were stratified according to extent of resection and surgical stage, and randomized to treatment or placebo. Adjuvant treatment consisted of a single dose of BCG (Tice) injected into the pleural space between days 6 and 12 postoperatively. Isoniazid was given by mouth for 12 weeks. In the control group saline was injected intrapleurally. Of 441 patients included in the study, 407 were evaluable, 198 of them in the BCG group and 209 in the control group. The average follow-up was 4.7 years. A high rate of complications was noted in the BCG group; after pneumonectomy 22% of these patients developed pleural empyema necessitating further surgical procedures, in comparison with 3% in the placebo group. There was no significant difference between the two randomized groups with respect to survival. There was, however, a significant decrease in the disease-free interval in patients who received BCG (P = 0.044). This detrimental effect with BCG was especially pronounced in pneumonectomized patients (P = 0.028). There was no significant difference between treatment and placebo in patients with lobectomies. Because of no proved benefit of regional administration of BCG (and even of detrimental effects after pneumonectomy) and a high rate of severe complications, the authors advise against the use of BCG intrapleurally as local adjuvant immunostimulation. PMID- 2876769 TI - Gastroesophageal reflux: clinical presentations, diagnosis and management. AB - Symptomatic gastroesophageal reflux occurs daily in an estimated 7% of adults and weekly or monthly in 29%. Untreated it can lead to esophageal erosions, ulceration and stricture formation. The pathogenesis is often multifactorial: defects in the function of the lower esophageal sphincter, esophageal clearance mechanisms and gastric emptying combine to produce frequent lengthy periods during which the lower esophagus is bathed in regurgitated acid. In most patients reflux disease is easily recognized as recurrent heartburn, regurgitation or dysphagia, or a combination. When acute chest pain or respiratory illness is the primary presenting complaint the patient needs particularly careful investigation to determine whether the symptoms are due to a primary cardiac or respiratory condition, are secondary to gastroesophageal reflux alone or represent a combination of disorders. Endoscopy with biopsy and long-term pH monitoring are the most reliable ways of determining whether reflux disease is present. Additional investigations, such as exercise testing, cardiac catheterization or inhalation challenge, may be needed in patients with cardiac or respiratory symptoms. Treatment should follow a stepped-care approach and in most patients should begin with changes in lifestyle, including dietary manipulation, reducing alcohol and cigarette consumption, and raising the head of the bed, together with appropriate use of antacids or alginate-antacid combinations. H2-receptor antagonists and agents to improve both gastric emptying and the tone of the lower esophageal sphincter may be added in sequence. Most patients will respond well to this regimen. Surgery should be considered only for those with intractable symptoms or with complications (e.g., stricture formation, bleeding, development of dysplastic epithelium in those with Barrett's esophagus, or secondary pulmonary disease that does not respond to medical management). It is successful in 85% of well-selected patients and has few complications. PMID- 2876772 TI - Intrapleural and intravenous Corynebacterium parvum in patients with resected stage I and II non-small cell carcinoma of the lung. The Ludwig Lung Cancer Study Group. AB - A prospective randomized trial compared the administration of intrapleural plus intravenous Corynebacterium parvum (C. parvum) versus placebo in patients with resected Stage I and Stage II non-small cell bronchogenic carcinoma. Treatment consisted of 7 mg C. parvum injected into the pleural space and 7 mg C. parvum intravenously once between days 6 and 12 postoperatively and 7 mg intravenously every 3rd month during the 1st year. Intrapleural administration of 35 cc of saline served as the placebo and the flush after intrapleural C. parvum. Of the 303 patients entered into this study, 286 were evaluable, with an average follow up time of 3.5 years. More complications, especially fever, were observed in patients receiving C. parvum. A fever greater than 38 degrees C was observed in 9% of the patients assigned to placebo and 76% of the patients assigned to C. parvum. There was no significant difference between the treatments with respect to disease-free interval or survival. PMID- 2876774 TI - Antihypertensive agents and cardiovascular risk factors. AB - A number of recent studies have failed to show the expected effect that aggressive antihypertensive therapy can contribute to the primary prevention of morbidity and mortality from coronary heart disease. Although antihypertensive agents effectively lower blood pressure, their ability to increase other cardiovascular risk factors may modify or even outweigh the beneficial effect gained from blood pressure control alone. In view of the vast population of patients with mild to moderate hypertension that might be treated, it is important that treatment of hypertension have as little adverse effect as possible on other risk factors. Current investigations have revealed that thiazide diuretics raise total cholesterol levels, while beta-blockers raise triglyceride and lower high-density lipoprotein levels. Thus both drugs tend to worsen the patient's serum lipid profile. Diuretics also decrease renal perfusion and increase serum glucose and uric acid concentrations. Beta-blockers have been shown to decrease exercise capacity and left ventricular performance. It is apparent, therefore, that even with a beneficial reduction of blood pressure, these drugs may have undesirable effects as well, thus tainting the expected clinical benefit. For example, data from the Framingham study indicate that a persistent increase of 10 to 20 mg/dl in total serum cholesterol largely offsets the protection from coronary heart disease afforded by a 10- to 15-mmHg reduction in blood pressure. Alpha 1-blocking agents, in contrast, appear to have desirable effects on many of the risk factors. The use of antihypertensive agents that do not adversely affect coronary heart disease risk factors, coupled with nonpharmacological measures such as diet and exercise, appears to be the best approach to therapy in hypertensive patients. PMID- 2876773 TI - Effects of radiation on host-tumor interactions using the multicellular tumor spheroid model. AB - Use of the multicellular tumor spheroid as a tumor model allows separate host or tumor treatment with ionizing radiation and examination of the effects on host tumor immune interactions. Spheroids of EMT6/Ro, a BALB/c mammary tumor were implanted into the peritoneal cavity of syngeneic immunized mice, recovered, and dissociated into single cells. Cytolytic activity of mature spheroid associated cells and peritoneal cells was resistant to radiation doses as high as 1000 rads when irradiate directly prior to assay. Mice irradiated (200, 400, 700 rads) 24 h prior to spheroid injection had an increased number of tumor cells and decreased number of tumor infiltrating and peritoneal host cells upon spheroid recovery. This was paralleled by an increased colony forming efficiency per spheroid. Cytolytic activity of the spheroid associated cells against radiolabeled EMT6 cells was in many cases decreased with radiation although lysis was the same on a per cell basis. Cytolytic activity by peritoneal cells from these mice increased with dose as measured on a per cell basis. This activity from irradiated animals was carried out by a Thy1+ cell. PMID- 2876775 TI - Double-blind comparison of tulobuterol and salbutamol in chronic obstructive pulmonary disease. AB - A double-blind study compared tulobuterol (2 mg BID), a new beta 2-adrenergic agent, with salbutamol (2 mg TID) in 40 hospitalized men with chronic obstructive pulmonary disease. The study evaluated the bronchospasmolytic effects of the two drugs and their selectivity of action. Measurements and observations were made for six hours after the first oral dose, daily during nine days of continuous therapy, and for 12 hours after the final dose on the tenth day. Results show that the tulobuterol regimen produced a significant (P less than 0.01) improvement of the forced expiratory volume in one second equal to an increase of 25% above the pretreatment value, versus 16% with the salbutamol regimen. Cardiovascular effects appeared more rapidly with tulobuterol, but they stabilized to values lower than those observed with salbutamol. No clinically important adverse reactions were reported other than slight tremor, which was not objectionable. PMID- 2876776 TI - Spironolactone in the treatment of hypertension: a review. PMID- 2876777 TI - Gene conversion involving the pilin structural gene correlates with pilus+ in equilibrium with pilus- changes in Neisseria gonorrhoeae. AB - Gonococci (Gc) exhibit pilus+----pilus- "phase transitions" at high frequency, but only some of the pilus- Gc can revert to pilus+ phenotype. We examined reversible phase transitions between pilus+ Gc and a particular pilus- variant (P rp+ phenotype) whose pilin mRNA carries a unique block of nucleotides encoding an "assembly missense" pilin polypeptide. The results show that Gc pilus+ in equilibrium with P-rp+ transitions can result from intragenic recombination in which there is nonreciprocal exchange of partially homologous DNA sequences from a partial pilin gene (in silent, storage form) into the expression locus' complete pilin gene. Hence Gc pilus phase variation, like pilus antigenic variation, can occur by gene conversion of the pilin structural gene expression locus. PMID- 2876778 TI - Control of bithorax complex functions by the segmentation gene fushi tarazu of D. melanogaster. AB - The properties of three dominant alleles of ftz are described. These alleles cause transformations of the first abdominal segment to the third and cause alternate segment pattern deletions that are out of phase with respect to those caused by ftz null alleles. To explain the effects of these mutations, a model is proposed in which ftz+ has two roles: to subdivide the body into parasegments and to activate appropriate bithorax complex functions in alternate parasegments. According to this model, the effects of the novel ftz alleles can be understood as arising from a slight widening of the blastoderm stripes of ftz expression. PMID- 2876779 TI - A gap gene, hunchback, regulates the spatial expression of Ultrabithorax. AB - We have examined the distribution of Ultrabithorax (Ubx) proteins in embryos mutant for the zygotic gap class of segmentation genes. Members of this class include hunchback (hb), knirps (kni), and Kruppel (Kr). All three mutations disrupt segmentation in specific regions of the embryo. Mutations in kni and Kr produce complex alterations in the Ubx expression pattern. In hb mutants Ubx is ectopically expressed both anterior and posterior to its wild-type boundaries. Thus, the hb gene may play an important role in the specification of the boundaries of Ubx expression. Using the Ubx protein distribution as a marker for metameric organization and using Hoechst dye to monitor cell death, we could follow early events that lead to the final gap-segmentation phenotype in the larval cuticle. PMID- 2876780 TI - Structural characterization of the TAP molecule: a phosphatidylinositol-linked glycoprotein distinct from the T cell receptor/T3 complex and Thy-1. AB - Here we characterize the T-cell-activating protein (TAP), an Ly-6 gene product involved in T cell activation, as a glycoprotein with a molecular weight of 10-12 kd under nonreducing conditions and 15-18 kd under reducing ones. Two of the three bands that are precipitated from metabolically labeled cells are expressed on the cell surface and can be recovered from the supernatants of cells treated with a phosphatidylinositol-specific phospholipase C. Thus TAP appears to be attached to the cell membrane via this lipid. Precisely the same anchorage is observed for the activating Thy-1 molecule, and is therefore of particular interest as a potentially novel linkage involved in membrane signal transduction. PMID- 2876782 TI - Phototoxic potential of mequitazine, a phenothiazine derivative, as determined by the photosensitized action on microbiological systems. AB - In order to determine phototoxic potential of mequitazine (MQZ), a phenothiazine derivative, in vitro tests were attempted using microbiological systems. When Escherichia coli was irradiated with ultraviolet-A light in the presence of MQZ, the surviving fraction was decreased with increasing fluence. Irradiation of bacteriophage lambda in the presence of the drug decreased the surviving fraction as well. Possible targets for the photosensitized action in these systems were discussed. PMID- 2876781 TI - Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. AB - Resistance of tumor cells to multiple cytotoxic drugs is a major impediment to cancer chemotherapy. Multidrug resistance in human cells is determined by the mdr1 gene, encoding a high molecular weight membrane glycoprotein (P glycoprotein). Complete primary structure of human P-glycoprotein has been determined from the cDNA sequence. The protein, 1280 amino acids long, consists of two homologous parts of approximately equal length. Each half of the protein includes a hydrophobic region with six predicted transmembrane segments and a hydrophilic region. The hydrophilic regions share homology with peripheral membrane components of bacterial active transport systems and include potential nucleotide-binding sites. These results are consistent with a function for P glycoprotein as an energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells. PMID- 2876783 TI - The behavior of 1,4-benzodiazepine drugs in acidic media. VI. Hydrogen exchange reaction and proton and carbon-13 nuclear magnetic resonance spectra of estazolam. PMID- 2876785 TI - Investigations on the carcinogenicity of fusarin C--a mutagenic metabolite of Fusarium moniliforme. AB - The cancer initiating potential of fusarin C, a mutagen produced by Fusarium moniliforme strain MRC 826 was investigated on mouse skin using 12-O tetradecanoylphorbol-13-acetate as promoter. In neither of these models did fusarin C act as a cancer initiator. Culture material of strain MRC 826, which previously was found to be hepatocarcinogenic in rats, exhibited cancer promoting activity in rat liver using diethylnitrosamine (DEN) as initiator and the induction of gamma glutamyltranspeptidase (GGT)-positive foci as end-point. The culture material of this fungus could also induce the formation of GGT positive foci without DEN initiation. These results seem to indicate that fusarin C is not involved in the hepatocarcinogenic activity of F. moniliforme strain MRC 826. PMID- 2876784 TI - Dinitrotoluene isomer-specific enhancement of the expression of diethylnitrosamine-initiated hepatocyte foci. AB - Technical grade dinitrotoluene (TDNT) was shown to be a potent hepatocarcinogen in rats; however, ambiguous results were obtained from bioassays which evaluated 2,4-DNT, the principal isomer in the technical mixture. The present studies were designed to determine the relative hepatocyte foci promoting activity of TDNT and the primary isomers present in the technical mixture, 2,4- and 2,6-DNT. A rat hepatic initiation-promotion protocol was used in which male Fischer-344 rats were initiated with a single dose of diethylnitrosamine (DEN) (150 mg/kg, i.p.) and permitted to recover for 2 weeks. Following the recovery period, the animals were fed diets containing TDNT,2,4-DNT,2,6-DNT or phenobarbital (PB). The TDNT animals were killed after 3 or 6 weeks of feeding and the 2,4-DNT-,2,6-DNT-and PB treated animals were killed after 6 or 12 weeks of feeding. Appropriate DEN and DNT controls were also killed at each time point. Sections from three liver lobes of each animal were stained for gamma-glutamyl transferase (GGT) and the number of GGT+ foci per cm3 (Nv) was calculated using stereological methods. TDNT feeding produced a dose-dependent increase in GGT+ foci (Nv) at 3 and 6 weeks relative to both DEN and TDNT controls. Administration of 2,4-DNT and PB produced time-dependent increases in GGT+ foci (Nv), while 2,6-DNT produced dose- and time dependent increases. Unlike 2,4-DNT and PB, the high dose (14 mg/kg) of 2,6-dNT produced an increase in GGT+ foci in the control groups and in mean foci volume relative to the DEN control. These results establish that TDNT, 2,4-DNT and 2,6 DNT have hepatocyte foci promoting activity and that 2,6-DNT is approximately 10 times more potent than 2,4-DNT. In addition, TDNT administration neither alters hepatocyte replication following partial hepatectomy nor acts as a 'growth selection' agent in the Solt-Farber 'growth selection' model suggesting that differential effects on hepatocyte replication are not responsible for the promoting activity of TDNT. Based on previous initiation study results from our laboratory and the present data, 2,6-DNT appears to be a complete hepatocarcinogen while under the conditions of these studies 2,4-DNT is an apparent 'pure promoter'. These results provide an explanation for the conflicting DNT bioassay results. PMID- 2876786 TI - The effect of diet on 2,6-dinitrotoluene hepatocarcinogenesis. AB - Pectin-induced changes in microflora have been shown to elevate the covalent binding of 2,6-dinitrotoluene (2,6-DNT)-related materials to total rat hepatic macromolecules. Therefore, the effect of diets varying in pectin content on the induction of foci and hepatic tumors induced by 2,6-DNT was studied in male F344 rats. 2,6-DNT (3.0-3.5 and 0.6-0.7 mg/kg/day) was incorporated into NIH-07 (NIH), an open formula cereal-based diet high in pectin content, AIN-76A (AIN), a purified pectin-free diet, or AIN-76A supplemented with 5% pectin (AP). Hepatic foci were scored after histochemical staining for gamma-glutamyl transpeptidase (GGT), canalicular adenosine triphosphatase or glucose-6-phosphatase following administration of test diets for 3, 6 and 12 months. The number of foci per cm3 of liver increased in a dose- and time-department manner following incorporation of 2,6-DNT into test diets with NIH greater than AP greater than AIN. In the NIH diet, 2,6-DNT did not alter the phenotypic distribution of foci. Animals fed control or 2,6-DNT-containing AIN and AP diets had few or no GGT foci throughout the study. Hepatocellular carcinomas and neoplastic nodules were observed only in rats fed NIH containing 2,6-DNT. The concentrations of 2,6-DNT-related material covalently bound to hepatic macromolecules after a single oral dose of radiolabeled 2,6-DNT given after 12 months on the diets increased in control rats and in rats receiving low dose 2,6-DNT in the diet with AIN less than AP less than NIH. These studies show that the carcinogenicity of 2,6-DNT differs depending on whether rats are fed an NIH or AIN (+/- pectin) diet. The results suggest that diet-induced alterations in the covalent binding of 2,6-DNT are not the sole factor in determining the carcinogenic response to 2,6-DNT. Furthermore, unidentified contaminants in cereal-based diets may influence foci and tumor production in rat liver during carcinogen treatment. PMID- 2876787 TI - Uptake of taurocholate by isolated gamma-glutamyltranspeptidase positive, putatively preneoplastic hepatocytes from 2-acetylaminofluorene treated rats. AB - Uptake of the bile acid taurocholate was determined in liver cells isolated from male Wistar rats fed a standard diet or a diet containing 2-acetylaminofluorene (2-AAF). In addition, uptake was analysed in unaltered, gamma glutamyltranspeptidase (gamma-GTase) negative, and in putatively preneoplastic, gamma-GTase positive, hepatocytes separated from the total liver cell preparation isolated from the 2-AAF-treated animals. Total hepatocytes from the carcinogen treated rats showed a approximately 50% decrease in the maximum rate of taurocholate transport compared to cells from untreated animals. Bile acid uptake in gamma-GTase positive and negative liver cells revealed that Vmax was decreased by 44 +/- 14% in the preneoplastic cell population. Since the Km value did not differ significantly it appears that the number of carrier molecules is reduced in the early preneoplastic hepatocytes. Our results show a partial loss of a liver-specific function in early preneoplastic gamma-GTase positive hepatocytes. PMID- 2876788 TI - Beta 1- and beta 2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure. AB - We used radioligand binding techniques and measurement of beta-agonist-mediated positive inotropic responses in isolated cardiac tissue to examine beta adrenergic-receptor subpopulations in nonfailing and failing human left and right ventricular myocardium. In tissue derived from 48 human hearts the receptor subtypes identified in nonfailing ventricle by radioligand binding were beta 1 (77%) and beta 2 (23%), with no evidence of an "atypical" beta-adrenergic receptor. In failing left ventricle the beta 1:beta 2 ratio was markedly different, i.e., 60:38. This decrease in the beta 1 proportion and increase in the beta 2 proportion in the failing ventricles were due to a 62%, "selective" down-regulation of the beta 1 subpopulation, with little or no change in beta 2 receptors. In muscle bath experiments in isolated trabeculae derived from nonfailing and failing right ventricles, both beta 1- and beta 2-adrenergic receptors were coupled to a positive inotropic response. In nonfailing myocardium, beta 1 responses predominated, as the selective beta 1 agonist denopamine produced a response that was 66% of the total contractile response of isoproterenol. In heart failure the beta 1 component was markedly decreased, while the beta 2 component was not significantly diminished. Moreover, in heart failure the beta 2 component increased in prominence, as the contractile response to the selective beta 2 agonist zinterol increased from a minority (39%) to a majority (60%) of the total response generated by isoproterenol. We conclude that failing human ventricular myocardium contains a relatively high proportion of beta 2 receptors, due to selective down-regulation of beta 1 receptors. As a result, in the failing human heart the beta 2-receptor subpopulation is a relatively important mediator of inotropic support in response to nonselective beta-agonist stimulation and is available for inotropic stimulation by selective beta 2 agonists. PMID- 2876789 TI - Measurement of human growth hormone (hGH) using a rapid immunochemiluminometric assay. AB - A two-site immunochemiluminometric assay for human growth hormone has been developed based on the use of chemiluminescent acridinium ester labelled monoclonal antibodies and a magnetisable particle - polyclonal antibody solid phase. The assay has an incubation time of 1 h at room temperature and rapid separation and quantitation stages. The sensitivity of detection is 0.12 mU/l and the working range is 0.88 to greater than 100 mU/l for inter-assay CVs less than or equal to 15%. The assay is convenient both technically and clinically since the wide range of growth hormone levels seen in growth hormone deficiency and acromegaly can be quantified accurately in a single test without the need for repeated sample dilution. PMID- 2876790 TI - 5-amino-2-nitrobenzoic acid as a reference material for the determination of gamma-GT activity. PMID- 2876791 TI - Brain renin angiotensin system contributes to the salt-induced enhancement of hypertension in SHR. AB - The study was performed to determine whether the brain renin angiotensin system may contribute to the acceleration in hypertension following long-term salt loading in spontaneously hypertensive rats (SHR). Five weeks old SHR and normotensive Wistar-Kyoto (WKY) were given 1% NaCl solution or plain tap water as drinking for 7 weeks. The salt treatment exaggerated the development of hypertension in SHR, but did not change the blood pressure (BP) in WKY. The hypotensive actions of intracerebroventricular (ICV) captopril was greater in SHR treated with salt than in those without treatment, whereas ICV AII increased BP to a similar degree between salt and control SHR. In WKY, the effects of ICV captopril and AII were not altered by the salt loading. The increases in BP induced by ICV hypertonic saline were not different between the rats with and without saline drinking in either SHR or WKY. The intravenous (IV) hexamethonium led to a greater fall in BP in SHR treated with saline than in those without salt, while it tended to produce a smaller decrease in BP in WKY with salt overload than in those without loading. Both duration and magnitude of the depressor effects of IV captopril were reduced by the chronic saline treatment in SHR. The plasma renin concentration (PRC) in both SHR and WKY was significantly suppressed by the salt load. The present results suggest that long-term salt overload may result in the enhanced activity of brain renin angiotensin system, which could be responsible for the exaggerated development of hypertension in SHR. Our observations also provide further evidence that the central renin angiotensin system is independent of the peripheral system. PMID- 2876792 TI - The treatment of acromegaly. PMID- 2876793 TI - Suppressed colony formation of peripheral blood lymphocytes in a patient with somatostatinoma. AB - The in vitro clonal growth of T lymphocytes was examined in a patient with somatostatinoma over a period of 8 months. After phytohemagglutinin stimulation colony-forming unit T lymphocytes could not be detected as compared to healthy controls and patients with metastatic colon tumors. The somatostatin produced by this tumor was identified as somatostatin-14. Synthetic somatostatin-14 inhibits significantly the colony formation and the tritiated thymidine incorporation of human peripheral T lymphocytes obtained from healthy subjects, suggesting immunoregulative properties of this neuroendocrine peptide. PMID- 2876795 TI - Ventilation/perfusion mismatch of one lung in a patient with Takayasu's arteritis. PMID- 2876794 TI - Studies on ergometer exercise testing. II. Effect of previous myocardial infarction, digoxin, and beta-blockade on exercise electrocardiography. AB - The results of exercise electrocardiography were studied in a random sample of 317 subjects with clinical suspicion of coronary artery disease. In 278 patients with coronary artery disease the rate of false negative tests was 18% with and 12% without previous myocardial infarction. If ST elevation was considered a negative response, the corresponding values were 25% and 13%, respectively, p less than 0.01. The greatest prevalence of negative tests was seen after anterior myocardial infarction: 27% or 42% when ST elevation was not included into positive responses. The sensitivity of exercise-induced ST depression for the presence of multivessel disease was lower after anterior infarction (67%) than in other patients with previous infarction (86%), p less than 0.01. The corresponding specificities were 71% and 22%, respectively, p less than 0.005. If ST elevation was included into positive responses these differences were abolished. In subjects without myocardial infarction the sensitivity was 89% and specificity 43%. Digitalized patients had somewhat higher sensitivity in the exercise electrocardiogram than those without digoxin, 90% vs. 81% (p less than 0.05), but the difference was not seen with exclusion of ST elevation. The specificity was not influenced by digitalis. beta-blockade had no effect on the sensitivity or specificity, but the prevalence of postexercise ST evolution was lower with (11%) than without (30%) beta-blockade. The prevalence of slowly ascending ST depression was reduced by three factors: the presence of digitalis in patients without previous myocardial infarction, infarction itself, and the extent of coronary artery disease. We conclude that exercise electrocardiography has only a limited value in prediction of multivessel disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876797 TI - Reconstruction of foot injuries. AB - Foot injuries constitute a spectrum of problems that can be classified by severity. The development of successful techniques for the treatment of lower leg injuries has made the severity of a concomitant foot injury a key factor in determining the overall salvageability of the leg. A more complete classification of foot injuries is therefore needed and has been proposed. Preoperative assessment of foot injuries differs in the acute versus the delayed presentation. The acute case requires evaluation of wound conditions, exposed structures, and associated proximal injuries. The chronic injury requires gait analysis, study of weight-bearing patterns by Harris mat prints, skeletal evaluation, mapping of plantar sensation, and, in some cases, angiography. Thorough knowledge of foot anatomy is essential for developing a rational plan for treatment. The significance and course of the medial calcaneal nerve and the anatomy of the plantar nerves have not been fully appreciated in most reports on the treatment of foot injuries. The recognition of the proximal plantar subcutaneous plexus blood supply has modified the understanding of plantar flap design. It has simplified and improved the safety of dissection of sensate plantar flaps. A plethora of both local and distant flap options exist for the treatment of foot injuries. The foot is divided into four major areas based on different requirements for reconstruction and the types of flaps available. These areas are the proximal plantar area; the malleoli, Achilles tendon, and posterior (non weight-bearing) heel area; the distal plantar area; and the dorsum. The options for coverage have been discussed in detail, and a summary of the reconstructive strategy by area has been presented in Table 3. Complex (type III) injuries are special injuries owing to their severity and multiple components. They require a careful initial evaluation for both feasibility and advisability of extremity salvage. Treatment of these injuries consists of bony stabilization and soft tissue debridement followed by flap coverage. PMID- 2876796 TI - Alpha-1-adrenergic blockade and lipoprotein metabolism in essential hypertension. AB - The effect of the selective alpha 1-antagonist terazosin on serum lipoproteins and certain blood pressure-regulating factors was assessed in 15 patients with essential hypertension. Terazosin given during 8 weeks reduced arterial pressure (from 153/103 +/- 3/2 (SE) to 143/96 +/- 5/2 mm Hg; P less than 0.02) but did not modify body weight, heart rate, blood volume, plasma renin activity, aldosterone and catecholamine levels, or serum cholesterol, triglycerides, and their lipoprotein fractions. In nine of the patients, blood pressure control was not achieved with terazosin monotherapy and the diuretic methyclothiazide, 2.5 mg, was added. After 8 weeks of combined treatment, blood pressure decreased further (P less than 0.05); serum lipids and lipoprotein fractions did not change as compared with placebo or terazosin conditions. These findings indicate that terazosin in monotherapy does not unfavorably influence lipid metabolism. PMID- 2876798 TI - Respiratory pharmacology. Beta-adrenergic drugs. AB - This article reviews the enormous literature on beta agonists, emphasizing three aspects: the structural, pharmacokinetic, pharmacodynamic, and toxicologic properties that are essential for understanding the clinical application of these drugs; the relative advantages and disadvantages of various routes of administration, including the different ways of prescribing the aerosols; and the pharmacologic factors that may limit the further development of these compounds for therapy. PMID- 2876799 TI - The classic antihistamines (H1 blockers) in respiratory medicine. AB - For almost a quarter of a century, the pharmacology of H1 blockers remained quasi stagnant, isolated from the rapid evolution of clinical pharmacology. However, exciting new developments concerning the role of histamine in asthma, and special pharmacodynamic features of new H1 blockers, have revived our interest in these drugs. PMID- 2876800 TI - Alternative drug therapy for asthma. AB - Individualized management of asthma requires consideration of single or combined pharmacologic alternatives. This article reviews experimental and clinical data on the efficacy, safety, mode of action, and therapeutic indications for cromolyn and related inhalational compounds; ketotifen; alpha-adrenergic blockers; calcium channel blockers; nonsteroidal anti-inflammatory drugs; and such diverse agents as immunosuppressive drugs, ether, alcohol, ascorbic acid, and other nutritional substances. PMID- 2876801 TI - The pharmacology of respiratory depressants and stimulants. AB - This article reviews the pharmacology and respiratory actions of depressants and stimulants, and the use of these drugs in the management of dyspnea, respiratory failure, and sleep apnea syndrome. PMID- 2876802 TI - Transduction mechanisms in chemoreception. PMID- 2876803 TI - Transport of galactose and sodium across lizard duodenum. AB - Electrical parameters and transepithelial Na+ and galactose transport were determined in vitro across isolated duodenum of Lacerta galloti lizard. Electrical potential difference (PD) and short-circuit current (Isc) were dependent on the presence of Na+ in the bathing solutions. PD and Isc were affected by addition of galactose to the mucosal solution. Isotopic flux of Na+ measurements across short-circuited duodenum showed a net active Na+ absorption. The net flux of Na+ (JNa+net) accounted for the observed Isc. Both (JNa+net) and Isc were increased by the addition of galactose 5 mM to the mucosal solution. Isotopic flux galactose measurements in open-circuit conditions showed a net active galactose absorption. The net transport of galactose was decreased to zero in the absence of Na+ in mucosal and serosal reservoirs. Galactose has been used to induce changes in short-circuit current (delta Isc) across intestine. delta Isc was a hyperbolic function of galactose concentration characterized by the parameters Vmax (maximum change in delta Isc) and Km (concentration needed to attain a velocity equal to half the Vmax). PMID- 2876804 TI - Maltase-glucoamylase and trehalase in the rabbit small intestine and kidney brush border membranes during postnatal development, the effects of hydrocortisone. AB - Kidney and intestinal brush border membranes were isolated from 14-day-old rabbits and papain solubilized maltase-glucoamylase was purified to almost homogeneity from both membranes. Maltase-glucoamylase from kidney and intestine have the same molecular weight (669,000 daltons by AcA 22 gel filtration) and the same Km (4 mM, for maltose). Tris (Ki = 12.5 mM, for maltose) is a non competitive inhibitor for both enzymes. In intestine, maltase and glucoamylase have low activity during the first two postnatal weeks and then undergo a sharp increase during the next 2 weeks. In contrast, for trehalase, adult levels are reached about 6 days after birth. Hydrocortisone injection to 10 days rabbits causes precocious increases in the specific activities of trehalase (3.6 x), maltase (5.2 x) and glucoamylase (7.4 x). Conversely, kidney maltase, glucoamylase and trehalase activities rise gradually from birth, reaching adult levels by the end of the third week. Administration of hydrocortisone to suckling rabbit does not affect either trehalase or maltase and glucoamylase in kidney brush border membrane. PMID- 2876805 TI - A preliminary note on the use of milk substitutes in the early weaning of dromedary camels. AB - The experiment was performed using two young male camels which weighed 24 and 36 kg respectively at birth. Each young camel was weighed and abruptly separated from its mother after 30 days of nursing (or at 1 month of age). The weaned calves were fed milk substitutes prepared commercially for lambs by Mabarot Chemical and Veterinary Products (Israel). The weanling camels averaged daily weight gains of 0.400 and 1.0 kg per day respectively during the 30 day initial period when the milk substitutes were used. Following the period when milk substitutes were used, the camels achieved normal growth to arrive at 135 and 145 kg respectively at 6 months of age. PMID- 2876806 TI - An analysis of the bursting behaviour of the Aplysia R15 neurone during exposure to normoxia and hypoxia with and without external calcium present. AB - Membrane potentials (EM), interburst intervals (IBI), burst durations (BD), the numbers of spikes within a burst, and the amplitudes of the burst pacemaker potentials (BPP) were measured in two groups (N = 7 per group) of R15 neurones under conditions of 20, 10 and 5% oxygen and under nitrogen equilibration in suffusates with either Ca2+ (10 mM) or Mg2+ (10 mM) present (Groups I and II). Under normal extracellular Ca2+ conditions, EM and the amplitude of the BPP for Group I R15 neurones increased progressively during hypoxia and reoxygenation. In the absence of external calcium, the normal bursting pattern of Group II R15 neurones was interrupted. No consistent relationships were observed among BD, IBI, and the number of spikes per burst with respect to EM or BPP. Hypoxia may alter the resting permeability of R15 to potassium as well as having ephaptic effects. PMID- 2876807 TI - Electrocardiograms recorded from the body surface of the carp, Cyprinus carpio. AB - The electrocardiograms (ECGs) in five kinds of bipolar leads were recorded from the body surface of the carp under water. Each component constituting the ECG wave could be detected by the present method. The potentials of the ECGs recorded by the present method were relatively small, the values being 2-64 microV. The electrical axis in most carp was directed toward the right lateral side. PMID- 2876808 TI - The digestive strategy and efficiency of the West Indian manatee, Trichechus manatus. AB - During the winters of 1982/83 and 1983/84, samples of digesta were collected from nine sites along the gastrointestinal tracts of seven West Indian manatees, Trichechus manatus. The voluminous large intestine of the manatee is responsible for considerable water reabsorption, as well as being the major site of organic matter, nitrogen and crude fat digestion. Cellulose digestion occurs primarily in the cecum and anterior portion of the colon in a pattern similar to terrestrial nonruminant herbivores like the horse. Overall digestibility coefficients for organic matter (71%), nitrogen (61%) and crude fat (77%) are comparable to those of terrestrial herbivores. Manatees have one of the highest digestibility coefficients for cellulose (80%) of any known mammalian herbivore. This high efficiency of cellulose digestion is due primarily to an extremely slow rate of passage. In addition, it appears that seagrasses may be more digestible than terrestrial forages, possibly due to their relatively low lignin content. PMID- 2876809 TI - Apical membrane potentials and intracellular potassium and sodium activities in the gallbladder of the freshwater turtle Mauremys caspica. AB - Open-tip and liquid ion-exchanger microelectrodes were used to measure transapical membrane potential (Va), fractional voltage ratio (fa) and intracellular sodium and potassium activities (aiNa, aiK) in Mauremys caspica gallbladder under open circuit conditions. The average values (+/- SEM) for Va and fa were -32 +/- 3 and 0.20 +/- 0.03 mV respectively. aiNa and aiK were, respectively, 17 +/- 4 and 82 +/- 7 mM. These results suggest that the mechanisms of Na+ and K+ transport in this tissue are essentially similar to those observed in leaky epithelia in general. PMID- 2876810 TI - Changes in conduction within the diffuse sinoatrial node of the chicken following premature atrial stimulation. AB - Premature atrial stimulation was used to estimate sinoatrial conduction within the diffuse sinoatrial node of the bird (chicken), and compare its conduction with that reported for mammals. While sinoatrial conduction could not be determined in the chicken because reset did not occur, the premature wavefront did have an effect on the sinoatrial node because the recovery interval following the premature stimulus became less than compensatory with shortening of the premature stimulus interval. This less than compensatory non-reset recovery interval is interpreted as a conduction dependent response in which the intrinsic wavefront leading to the first recovery atrial activation conducts out of the node faster than normal. This conduction dependent recovery interval is seen infrequently in mammals (rabbit, dog and man). The absence of reset and the presence of a less than compensatory non-reset response in the chicken suggests that while the general organization of the sinoatrial node of the chicken is similar to that in mammals, a larger transitional cell network in the chicken prevents a premature wavefront from reaching the pacemaker cells and resetting them. PMID- 2876811 TI - Tissue glycogen and lactate handling by the developing domestic fowl. AB - The levels of glycogen and lactate in liver, intestine, yolk sac membrane and leg and breast muscle of domestic fowl from day 10 of "in ovo" development to day 5 after hatching compared with adults have been measured and compared with the circulating concentrations in blood of glucose and lactate. Glycogen stores in most tissues increased before hatching to attain a minimum around the eclosion and then increased to adult values in muscle and liver. Lactate maintained its plasma concentrations with higher effectiveness than plasma glucose, which increased steadily up to adult levels from hatching. The study of tissue vs plasma lactate concentration ratios suggests a general activation of lactate metabolism from hatching, coinciding with the ingestion of carbohydrate-based food. Both muscles studied, as well as intestine, seem to be net lactate producers; blood cells can speculatively be considered as lactate users and liver maintains its concentration of lactate very close to that plasma, suggesting a fast utilization of this material as well as liver being the main site for control of circulating lactate. PMID- 2876812 TI - Characterization of insulin binding to bovine liver and mammary microsomes. AB - Bovine liver and mammary gland (MG) appear metabolically independent of insulin, yet the specificity and kinetics of 125I-insulin (125I-INS) binding to bovine liver and MG microsomes (MIC) indicate the presence of insulin receptors in MIC from both tissues. The insulin receptors from bovine liver (Kd = 7.6 X 10(-10) M) and MG (Kd = 9.6 X 10(-11) M) were similar to each other and to other insulin receptors in their binding affinities and pH optima. Perturbation of rat liver and bovine MG MIC by phospholipase or NaCl treatment increased 125I-INS binding to the membranes, suggesting exposure of cryptic insulin receptors. Different responses in 125I-INS binding to membrane perturbation suggest differences between rat and bovine membranes. PMID- 2876813 TI - Absorption of 3-oxy-methyl-D-glucose by chicken cecum and jejunum in vivo. AB - Jejunal and cecal 3-oxy-methyl-D-glucose (3-OMG) absorption was studied in 4- to 8-week-old chickens by an in vivo perfusion technique (perfusion rate 1.5 ml/min). Total and phloridzin-insensitive 3-OMG absorption was tested for lumenal substrate concentrations ranging from 1.25 to 20 mmol/l. The estimated apparent Michaelis constants in jejunum and cecum were 5.1 and 4.0 mmol/l (Lineweaver-Burk method) and 3.2 and 3.1 mmol/l (visual inspection method), respectively. Vmax were similar in both segments with either method, about 0.3 mumol/cm2 X 5 min. Passive permeability coefficients were the same in both regions (about 45 l/cm2 X 5 min X 10(3)). The transport properties of the cecal epithelium in vivo suggest a role of these intestinal segments in the absorption of nutrients originated from digestive processes. PMID- 2876814 TI - Parental spleen cells accelerate the development of intestinal brush border structure and function in neonatal mice. AB - The influence of parental spleen cells on the postnatal development of brush border microvillus membrane structure and the ability to transport lysine and alanine has been studied in the mouse jejunum during the second week of postnatal life. Control tissue taken from 7-11 day old mice has an unchanging crypt-villus structure and a low enterocyte migration rate of about 1 micron hr-1. Microvillus elongation in crypt enterocytes takes 6 days to complete under these conditions. Lysine and alanine transport begin 2 days after structural differentiation has ceased. Parental spleen cells injected into 1-2-day-old F1 mice cause crypt cell hyperplasia, villus shortening and a 3-6-fold increase in enterocyte migration rate after a period of 8 days. These effects are associated with large reductions in the time needed to complete microvillus membrane development and first express absorptive function. Lysine and alanine transport begin approximately 6 hr after structural differentiation has ceased under these conditions. Adaptive changes in the development of enterocyte structure and function, induced by injection of parental spleen cells, bear some resemblance to other changes found to occur normally at weaning and in adult animals subjected to controlled changes in diet and environmental temperature. The possibility that common principles govern enterocyte adaptation and that some of these still apply in an intestine undergoing an immune reaction is discussed. PMID- 2876815 TI - Metabolic effects of radiation induced rat insulinoma at pancreatic, hepatic and subscapular transplantation sites. AB - Metabolic effects of 3 different sites of transplantation of cultured tumour cells from a radiation induced insulinoma (28 X 10(6) viable cells per rat) were examined in 15-18 weeks old male NEDH rats. Subscapular implantation consistently produced a highly vascularised encapsulated tumour associated with hyperinsulinaemia, hyperphagia and hypoglycaemia by 21 days, which progressed to fatal neuroglycopaenic coma at 37 +/- 3 days (mean +/- SEM). Implantation of tumour cells into the hepatic portal vein resulted in a multilobular hepatic tumour in two out of nine rats, with hyperinsulinaemia and fatal hypoglycaemia by 49-54 days. Irregularities of glucose homeostasis were observed in a further three rats by 62 days. Intrapancreatic implantation consistently produced a similar tumour to that observed at the subscapular site. Implantation into the pancreas produced the most rapid onset of hyperinsulinaemia, hyperphagia and hypoglycaemia, with survival for only 28 +/- 3 days. The results demonstrate an important effect of transplantation site on the function and metabolic consequences of the NEDH rat insulinoma. PMID- 2876816 TI - Fatty acids in the milk of goats after cessation of lactation. AB - Regular hand milking of six goats was discontinued after 32-35 weeks of lactation. A few days after milking out ceased, the concentration of triglyceride in peripheral blood plasma increased. Over a period of weeks, the concentration of triglyceride in small samples of fluid taken from the teat canal fell gradually. Lipase activity of the milk fluid was temporarily reduced shortly after milking out ended, but, despite this, its concentration of free fatty acids increased. It is suggested that free fatty acids are released during clearance of milk triglyceride from residual fluid in the mammary gland after cessation of lactation. PMID- 2876817 TI - Rearing rats (Rattus norvegicus) at 30 degrees C does not alter sensitivity to noradrenaline. AB - Rats reared from birth at 30 degrees C show a permanent deficit in body temperature regulation. To test the ability of heat-reared rats to respond to an adrenergic drive, carbon dioxide production was measured at five doses of noradrenaline in rats reared at either 20 or 30 degrees C. Noradrenaline-induced carbon dioxide production was greater at all doses in 20 degrees C rats, but sensitivity to noradrenaline was the same in heat-reared and control animals. These findings support the conclusion that the thermoregulatory deficit induced by heat rearing is due to a change induced in the nervous system. PMID- 2876818 TI - Ionic regulation in fish: the influence of acclimation temperature on plasma composition and apparent set points. AB - Published data on the influence of acclimation temperature on normal ionic concentrations in fish plasma are summarized. Although osmolality rises near 0 degree C in many marine fish, there is otherwise no general tendency in marine species for osmolality, Na and Cl to fall with increasing temperature. The suggestion that osmolality, Na and Cl in freshwater fish typically fall with decreasing temperature is not supported. K and Ca generally rise with increasing temperature, or stay constant. Mg generally falls with increasing temperature, or stays constant. Evidence on concomitant variations in set points is sparse, but apparent set points for osmolality/Na/Cl, except near 0 degree C, usually vary by less than +/- 2% degrees C-1. PMID- 2876819 TI - Evolutionary trends in sperm structure. AB - In the marine invertebrates which practise external fertilization, the spermatozoon is a flagellate cell, possessing an acrosomal complex made up of acrosome and perforatorium. In the animal phyla which adapted to land after having achieved internal fertilization the spermatozoon has acquired an elongated shape and develops accessory cytoskeletal organelles in the tail. In the highest forms, the flagellum seems to have become too long for perfect motility; in such a condition, aberrant axonemal patterns can appear and aflagellate spermatozoa can also be found. At the apex of the terrestrial phyla, alternative motile apparatuses have been achieved and also the acrosomal complex varies, according to the different structures of egg envelopes. PMID- 2876820 TI - Acidification of the bathing fluid by the skin of Rana pipiens in metabolic acidosis. AB - The skin of Rana pipiens can be shown to excrete H+ in an in vitro preparation. This H+ excretion is increased by placing the frog in metabolic acidosis. In addition, H+ excretion is increased by the presence of HCO-3-CO2 on the serosal or inside surface of the skin. Removal of Na+ from the outside bathing solution of the skin has no apparent effect on H+ excretion. Ouabain inhibits H+ excretion by the skin of acidotic frogs almost completely, in the absence of exogenous CO2. In the presence of 5% CO2 ouabain inhibits H+ excretion by 50%. In the acidotic frog skin the H+ excretion was reduced by abolishing the spontaneous potential difference. While in the normal skin there was no effect. When the P.d. was clamped at -10 to -100 mV there was no effect on H+ excretion, while there was a slight depression of H+ excretion when the P.d. was clamped at +10 to +100 mV (outside to inside the skin). In the presence of 5% CO2 there was a marked depression of H+ excretion when clamped at -10 to -100 mV in the normal skin. In metabolic acidosis there was a marked stimulation when clamped at -10 to -100 mV. PMID- 2876821 TI - Effects of acute cold exposure on rectal temperature, blood glucose and plasma free fatty acids in alloxan-diabetic rats. AB - These experiments were carried out to study the effects of acute cold exposure (0 2 degrees C/4 hr) on rectal temperature, blood glucose and plasma free fatty acids (FFA) in alloxan-diabetic rats. Male Wistar rats weighing 170-190 g were used and diabetes was induced by i.v. alloxan injection (40 mg/kg body wt). Cold exposure produced severe hypothermia in diabetic rats. After 4 hr of cold, blood glucose of diabetic rats was reduced from 296 +/- 16 to 86 +/- 12 mg/dl (P less than 0.01), and FFA increased slightly, but was not statistically different (P greater than 0.05) from the initial value. As expected, interscapular brown adipose tissue (IBAT) and retroperitoneal and epididymal white adipose tissues were significantly lower in diabetic than in control rats. Cold exposure reduced total IBAT lipids in control but not in diabetic animals. The results of this experiment suggest that diabetic rats were unable to maintain body temperature in the cold, probably because of a failure to generate an adequate amount of heat by nonshivering thermogenesis in brown adipose tissue. PMID- 2876822 TI - Bile pigment formation and excretion in the rabbit. AB - Bile and plasma levels of biliverdin and bilirubin, together with the hepatic biliverdin reductase and bilirubin UDP-glucuronosyl transferase activities, were studied in the rabbit. No biliverdin could be detected in the blood plasma. The bilirubin concentration in blood was 7.81 +/- 0.79 mumol/l. Biliverdin was the predominant pigment in bile (63%). Hepatic biliverdin reductase activity was 0.086 +/- 0.016 nmol/mg protein/hr. The synthesis of bilirubin was apparently limited by the enzyme activity. Most of the bilirubin in bile was conjugated (90%) with monoconjugates predominating (75%). Hepatic UDP-glucuronosyl transferase activity was 2.65 +/- 0.18 and 1.14 +/- 0.16 mumol/mg protein/hr with and without activation, respectively. PMID- 2876823 TI - Hemotypes in Spanish sheep breeds. AB - The structure and the genetic diversity of the Churra, Lacha and Manchega sheep breeds have been analysed using hemotypes observed in eight loci. The three breeds are different in their hemotypes in terms both of quantity and quality. The proportions of unique hemotypes in Churra (60%), Lacha (61%) and Manchega (67%) revealed a high level of individual diversity within each breed. Racial genetic diversity follows the descending order of: Manchega-Lacha-Churra. The value of N:H (number of animals: total hemotypes) in the multi-racial population was 3.05. PMID- 2876824 TI - Ciliary beating frequency of frog palate and rat trachea explants under continuous perfusion. AB - Rat trachea and frog palate explants were continuously perfused for 2 hr with 199 tissue culture medium. The ciliary beating frequency of the frog palate exhibited fluctuations twice as large as compared to the rat trachea. The rat trachea model should be preferred to the frog palate for long-term studies on ciliary beat frequency. PMID- 2876825 TI - Serum thyroxine and seasonal fattening of free-living Piute ground squirrels, Spermophilus mollis (Rodentia: Sciuridae). AB - Serum thyroxine and body composition of free-living Piute ground squirrels were examined during the season of above-ground activity. Serum thyroxine titers were 2-10 times higher than those reported in laboratory studies on other species. Among juveniles, both body size and lipid content were negatively correlated with thyroxine, whereas these variables were not significantly correlated among adults. Significant sex differences in serum thyroxine were observed for both age groups. Results suggest that the seasonal cycle of body weight is driven by an underlying metabolic cycle but that individual fattening schedules are determined by environmental conditions. PMID- 2876826 TI - Thermogenic effects of a "cafeteria" diet on the rat during its reproductive cycle. AB - The heat production and oxygen consumption of intact virgin, pregnant, lactating and postlactating rats has been investigated both in groups fed a "cafeteria" diet as well as in controls. A third group of rats fed the cafeteria diet after parturition has been investigated. Pregnant rats fed a "cafeteria" diet increased their weight faster than controls. During lactation no increases in weight were observed, and in postlactation both "cafeteria" groups attained the same values higher than controls. The ingestion of a "cafeteria" diet resulted in higher heat production in all groups except lactating rats, which--in addition--showed higher heat outputs than all the other groups when the actual data were corrected by metabolic weight according to the surface law. The high lactation heat production (and oxygen consumption) can be a consequence of increased metabolic activity in the rat organism, devoted to milk production. It can be concluded that during lactation the dam energy output through the milk must absorb any increases in energy input due to the more densely-packed energy in the "cafeteria" diet, and this did not result in increased heat production. PMID- 2876827 TI - The effects of ACTH and dexamethasone upon plasma thyroid hormone levels and heat production in the domestic fowl. AB - Treatment with long acting ACTH (20 IU kg-1) produces a large and sustained elevation of plasma corticosterone in the domestic fowl. Both ACTH treatment and administration of dexamethasone produce significant reductions in plasma concentrations of T4 and T3, and these changes are accompanied by a sustained hyperglycaemia. Despite the changes in circulating thyroid hormones only a small reduction in heat production (-14%) was induced by either treatment and mainly during the dark period. Whilst there may be some causal relationship between increased corticosterone secretion, decreased plasma thyroid hormone levels and reduced metabolic heat production it is unlikely that these responses alone account for the adjustments in energy expenditure observed in short term food deprivation. PMID- 2876828 TI - The effects of glucagon and insulin on plasma thyroid hormone levels in fed and fasted domestic fowls. AB - Glucagon injection (50 micrograms kg-1) produced a biphasic response in plasma thyroxine (T4) level in both fed and fasted chickens. An initial inhibition was followed by an increase to levels above control value. Glucagon reduced plasma triidothyronine (T3) possibly as a consequence of inhibition of peripheral monodeiodination. This inhibition persisted in fasted animals despite a glucagon induced hyperglycaemia. Insulin injection (4 IU kg-1) decreased plasma T4 concomitant with a profound hypoglycaemia. These effects were more pronounced in fasted birds. Insulin induced hypoglycaemia was associated with decreased plasma T3 probably as a consequence of reduced thyroidal T4 secretion and reduced peripheral monodeiodination. Glucagon and insulin may play direct or indirect roles in the regulation of thyroid hormone secretion and metabolism in the domestic fowl. PMID- 2876829 TI - Concentrations of carbohydrates and lipids of guinea pigs after five days starvation. AB - The concentrations of serum total lipids, cholesterol and triglycerides of guinea pigs were determined under normal conditions and after 5 days fasting. Serum glucose and liver glycogen levels were also estimated under both conditions. The amounts of serum total lipids and cholesterol were significantly increased as a result of starvation, whereas, fasting had no significant effect on serum triglycerides. Liver glycogen was rapidly decreased in response to starvation in a highly significant manner. However, starvation did not affect serum glucose of guinea pigs. PMID- 2876830 TI - The kinetics of calcium influx into rat liver slices. AB - The unidirectional influx of calcium across rat liver slices is a carrier mediated process which displays saturation kinetics. The presence of Mg2+ in the incubation medium competitively inhibits calcium influx into rat liver slices. Metabolic inhibitors such as ouabain and 2,4-dinitrophenol at a concentration of 1 X 10(-4) and 2.5 X 10(-4) M respectively, inhibited significantly (P less than 0.001) calcium influx across the liver slices. Calcium influx is dependent on the presence of sodium in the extracellular medium, and is significantly reduced (P less than 0.01) when sodium concentration in the preincubation solution is reduced to zero. PMID- 2876832 TI - Amino acid compartmentation in chick blood during the peri-hatching period. AB - Individual amino acid levels and compartmentation in chick blood were measured on day 20 of incubation, at hatching (day 0), or after 1 or 5 days of free life, and compared with those of adult chickens. Blood cell amino acid concentrations were almost one order of magnitude higher than those of plasma, with higher values than those found in mammalian erythrocytes. This difference may be due to the capability for protein synthesis of the nucleated cells coupled with a postulated utilization of amino acids as fuel. The most common pattern of individual plasma amino acid levels was a slight rise at hatching followed by a large decrease, with minimal values for adults. The patterns in the cells did not always coincide with those for plasma. Total blood amino acid levels increased steadily during the period studied due to the increase in intracellular amino acids, giving rise to increasing blood-cell/plasma concentration ratios. These changes showed higher availability of plasma amino acids just after hatching, while the cell concentrations increased steadily to the maximum values in adults. The increase in alanine levels in cells with little changes in plasma can be correlated with the role of this amino acid as the main 2-amino nitrogen carrier in the avian bloodstream. The high amino acid levels in the cells suggest that these cells act as inter-organ transporters and reservoirs of amino acids, they have a different role in their handling and metabolism from those of mammals. PMID- 2876831 TI - A comparison of the mineral composition of milk of domestic and captive wild equids (Equus przewalski, E. zebra, E. burchelli, E. caballus, E. assinus). AB - Milk samples were obtained in early and/or late lactation from Przewalski horses, Hartmann's zebras, Grant's zebras, domestic horses, ponies and a mule mare made pregnant by embryo transfer. Samples were compared for their content of total solids, ash, calcium, phosphorus, magnesium, sodium, potassium, copper, zinc and iron. Milk from the Przewalski horses, Hartmann's zebra and the domestic horse had similar mineral composition and the content of minerals was higher in early than in late lactation. Milk from the domestic mule contained the lowest concentration of calcium, phosphorus and zinc but the highest concentration of magnesium, sodium and potassium. Milk from the Grant's zebras contained more sodium than potassium, unlike milk from Przewalski horses, Hartmann's zebras or domestic horses in which there was more potassium than sodium. PMID- 2876833 TI - Avian hepatic T3 generation by 5'-monodeiodination: characterization of two enzymatic pathways and the effects of goitrogens. AB - The enzymatic nature of 5'-monodeiodination (5'-D) in avian liver homogenates was demonstrated by abolishment of activity by iopanoic acid (IOP). T3 production from T4 was dependent on enzyme and substrate concentrations, incubation time, incubation temperature, and pH. Two pathways of 5'-D activity were present in avian liver and exhibited characteristics similar to those described in mammalian tissues. Type II activity was identified as propylthiouracil (PTU)-insensitive activity. Type I (PTU-sensitive) was determined by difference between Total and Type II. Km values were 1.58 microM T4 for Total activity and 0.90 nM T4 for Type II, corresponding to the characteristics of the mammalian pathways. The effects of goitrogens on avian hepatic 5'-D were equivalent to those reported for the mammalian enzyme. PMID- 2876834 TI - Basal and HCG-stimulated testosterone production by interstitial cells of the Mongolian gerbil (Meriones unguiculatus)--I. Influence of preincubation length, medium composition and temperature. AB - In the absence of HCG, production of testosterone by whole testes superfused in vitro was quite constant during the 5-hr superfusion period. Addition of 23-184 mIU/ml HCG caused a significant increase of testosterone production which was apparent from 30 min after start of superfusion. Basal and HCG-stimulated testosterone production by whole testes was significantly higher (400, 1950 ng/testis/5 hr, without and with 100 mIU HCG) than by isolated cells (200, 1350 ng/testis/5 hr). Incubation of isolated interstitial cells in medium 199 supplemented with fetal calf serum (FCS), (N-2-hydroxyethylpiperazine-N-2 ethanesulphonic acid, HEPES) and 3-isobutyl-methylxanthine (MIX), and in medium 199 without FCS, HEPES or MIX, gave similar testosterone responses. While centrifugation at 8000 g for 2 min drastically diminished testosterone formation by isolated interstitial cells, production was similar by cells incubated in either 0.5, 1.0 or 1.5 ml medium. A significant decrease of testosterone synthesis by isolated interstitial cells was found when cells were stored at 4 degrees C for 2 days and then were incubated at 35 degrees C for 6 hr without or with 1-1000 microIU HCG. While isolated interstitial cells incubated at 5 degrees C did not produce testosterone at all, testosterone production increased to 49.5 +/- 3.9 ng/10(5) cells (30 degrees C) and 24.1 +/- 1.1 ng/10(5) cells (40 degrees C), respectively. HCG-stimulated testosterone production was maximal when interstitial cells were incubated at 34 degrees C. PMID- 2876835 TI - Basal and HCG-stimulated testosterone production by interstitial cells of the Mongolian gerbil (Meriones unguiculatus)--II. Influence of glucocorticosteroids and steroidal precursors. AB - Compared to testosterone production by Mongolian gerbil interstitial cells in the absence of HCG or precursors, testosterone formation was significantly elevated by the addition of 100 ng pregnenolone, progesterone, 17-hydroxyprogesterone or DHEA. Production increased linearly with the amounts of precursors added (pregnenolone: r = 0.99; progesterone: r = 0.98; 17-OH-progesterone: r = 0.96; DHEA: r = 0.92, N = 40, all P less than 0.001). Approximately 50% of DHEA were converted to testosterone during the 6-hr incubation period. Neither the addition of 100 ng 11-deoxycortisol, 11-deoxycorticosterone, cortisol, corticosterone, cortisone, 18-OH-corticosterone, 21-deoxycortisone or 11-dehydrocorticosterone, nor of 100 ng estradiol had a significant effect on testosterone production by isolated interstitial cells incubated without or with 1 mIU HCG. Testosterone production by isolated interstitial cells was significantly increased within 2 min after the addition of 100 ng DHEA; production then linearly increased with the length of incubation (r = 0.98, N = 40, P less than 0.001). After addition of as little as 2 ng DHEA, testosterone formation was higher than by cells incubated without DHEA. While testosterone production could not be stimulated by the addition of 1-500 microIU HCG during a 30-min incubation period, it was drastically elevated by the addition of 10, 20 or 100 ng DHEA. Steroidal precursor concentrations secreted by the Mongolian gerbil adrenal gland incubated in vitro for 120 min were too low to stimulate testosterone production by interstitial cells. On the other hand, testosterone synthesis could be increased by the addition of 10-100-microliter aliquots of adrenal extracts. PMID- 2876836 TI - The effect of chronic and acute dietary restriction on the growth and protein turnover of fast and slow types of rat skeletal muscle. AB - Changes in the growth and protein turnover of the anterior tibialis and soleus muscles were studied in response to acute and chronic dietary restriction (50% of ad libitum intake) between 3 and 149 weeks post partum. The effect of long-term dietary restriction from weaning to senescence was to retard the growth and normal developmental of the two types of skeletal muscle. This was evident from measurements of various parameters of growth, i.e. total protein, RNA and DNA and protein/DNA-P, which were reduced by approximately 50% when compared with age matched controls. These decreases, however, were not accompanied by a decline in the fractional rate of synthesis (%/day) or ribosomal activity (mg protein/day per mg RNAP). The slowing down of the age-related decline in muscle growth has been attributed to a reduction in RNA capacity (RNA/protein), with similar responses in the fast- and slow-twitch skeletal muscles. The initial effects of piecemeal feeding of this restricted diet on the two types of muscle were also monitored. Short term starvation effects, i.e. 24 hr after feeding a reduced ration, were measured on the protein content and RNA/protein of both the anterior tibialis and soleus muscles; both parameters were unchanged within 24 hr. In contrast, a rapid and significant decline in the ribosomal synthetic activity (mg/d per mg RNAP), and a corresponding fall in the fractional rate of synthesis, occurred within 24 hr of feeding. PMID- 2876837 TI - Artefactual and true uptake of labelled sucrose by rat pancreatic islet cells. AB - Labelled sucrose is currently used as an extracellular marker in pancreatic islets or isolated islet cells. Contamination of [6,6'(n)-3H]sucrose by tritiated hexose results in severe overestimation of the extracellular space. The relative magnitude of this overestimation depends on such factors as the temperature and length of incubation and the presence or absence of metabolized unlabelled hexose. Even with uncontamined [U-14C]sucrose, a restricted amount of the disaccharide is apparently taken up, hydrolyzed and further metabolized in the islet cells. The uptake of sucrose by islet cells may reflect the phylogenic maintenance of a physiological attribute of these primitively intestinal epithelial cells. PMID- 2876839 TI - Time-dependent influence of some sedating agents on basic haematological values in various artio- and perissodactylids. AB - Basic haematological values in 32 animals of five species were estimated after administration of sedating agents. In all species under investigation, a time dependent decrease of erythrocyte counts, haematocrit values and haemoglobin content was noted during the first 30 min after sedation, for the following 30 min the lowered values remained essentially without any change in zebras. Derived parameters, mean corpuscular haemoglobin, mean corpuscular Hb concentration and mean corpuscular volume did not change during the period of observation. Only insignificant changes in leukocyte count and in the proportion of lymphocytes and neutrophiles were registered. The shortest possible time between sedation and blood sampling is recommended to minimalize a distortion especially in the red blood picture. PMID- 2876838 TI - Comparative red blood cell metabolism in three wallaby species, Macropus eugenii, Macropus parma and Thylogale thetis (Macropodidae: Marsupialia). AB - Aspects of red blood cell metabolism were compared among three species of small macropodid marsupials from different habitats. Packed cell volume (PCV), erythrocyte reduced glutathione (GSH) concentration and GSH regeneration rates were similar in all three species. The Parma wallaby had very low red cell potassium levels compared to the other species studied. The Tammar wallaby had higher rates of glucose consumption and lactate production in vitro at both pH 7.4 and 8.2 than did the Parma and significantly lower adenosine triphosphate (ATP) levels than the other species. These findings are consistent with preliminary reports published previously. The differences noted cannot be directly related to differences in the habitats of the species. PMID- 2876841 TI - Biochemical studies of taste sensation--XII. Specificity of binding of taste ligands to a sedimentable fraction from catfish taste tissue. AB - The specificity of amino acid binding sites in a sedimentable fraction prepared from catfish taste epithelium was examined. Using seven 3H-labeled amino acids as ligands and the unlabeled amino acids in binding competition assays, the presence of possibly three classes of amino acid binding sites was deduced. Site 1 binds L THR, L-SER, L-ALA and possibly D-ALA and beta-ALA, Site 2 binds L-SER, L-ALA, GLY, D-ALA, and beta-ALA and Site 3 binds L-ARG and L-LYS. Additional evidence supporting the specificity of Site 2 was obtained from the specificity of enhancement of L-ALA binding. The results demonstrate the presence of some major classes of taste receptor sites, and provide a basis for understanding taste receptor specificity at the biochemical level. PMID- 2876840 TI - Influence of cholecystokinin, vasoactive intestinal peptide and secretin on plasma concentration of avian pancreatic polypeptide in laying hens. AB - The influence of saline infusion (i.v.) followed by infusion of either cholecystokinin, vasoactive intestinal peptide, or secretin on plasma concentration of avian pancreatic polypeptide (aPP) was studied in sixteen 18-26 week old Single Comb White Leghorn hens. Three concentrations were used for each hormone. Blood was drawn after both saline and hormone infusions and assayed for aPP content. No significant influence of any of the three hormones on plasma aPP level was found in either fed or fasted hens. PMID- 2876842 TI - Effect of starvation and a protein diet on the amino acid metabolism enzyme activities of the organs of domestic fowl hatchlings. AB - The activities of alanine and aspartate transaminases, adenylate deaminase, glutamine synthetase and glutamate and xanthine dehydrogenases have been measured in liver, yolk sac membrane, intestine and breast and leg muscle of domestic fowl hatchlings receiving for 3 or 5 days either a standard diet or hard boiled eggwhite as well as in 3 or 5 days starved animals. The patterns of activation of amino acid metabolism enzymes were fully comparable in protein-fed and starved groups with respect to fed controls; the differences with respect to the latter became more marked in 5- than in 3-days old chicks. In 5-days old chicks intestine alanine transaminase activity increased in parallel to that of liver in protein-fed animals but not in those starved, in agreement with an enhanced alanine transfer between both organs under this situation. Both, starvation and protein-feeding, induced a general decrease in the amino acid metabolizing ability of muscle. Glutamine (but not alanine) synthetizing capabilities were enhanced. PMID- 2876843 TI - Aspartate:2-oxoglutarate aminotransferase from Trichomonas vaginalis: comparison with pig heart cytoplasmic enzyme. AB - The aspartate:2-oxoglutarate aminotransferase from the protozoon Trichomonas vaginalis exists as a mixture of sub-forms of identical Mr and amino acid composition, and of similar catalytic properties. The amino acid composition closely resembles that of aspartate aminotransferase from prokaryotic and vertebrate sources. Some molecular and catalytic properties of the T. vaginalis aspartate aminotransferase are compared with those of the cytoplasmic pig heart enzyme. A major difference is in the ability of the trichomonal enzyme to transaminate aromatic amino acids and 2-oxo acids. A range of inhibitors have been used to compare the active-site regions of the T. vaginalis and cytoplasmic pig heart aspartate aminotransferases. PMID- 2876844 TI - Cardiac rhythm in cats during physiological sleep in experimental myocardial infarction and beta-adrenergic receptor blockade. AB - The authors investigated parameters of the sinus rhythm and of the structure of physiological sleep in 11 cats after ligation of the interventricular artery. ECG of the cerebral cortex, electromyogram, electrooculogram, ECG and respiration were registered, both in the acute period of infarction (4th-10th day of the experiment) and in the subacute and late period (3-12 months). In the acute and subacute period, an abrupt decrease was found in the sinus rhythm variability during the waking-sleep cycle. Propranolol administration (10 mg/kg) reduced in intact animals the heart rate, especially during wakefulness, and the rhythm variability during wakefulness and sleep. Suppression of sinus rhythm automatism due to propranolol in animals with experimental MI was most pronounced in the acute period during REM sleep, in the subacute period during wakefulness. In the acute period of MI, the sleep structure was disorganized, in the subacute period it got partly normalized. Protracted propranolol administration in the subacute period of MI led to disturbances in the sleep structure, with reduced REM sleep and prolongation of stage I-II (superficial sleep). PMID- 2876845 TI - Alzheimer's disease and related dementias: selective involvement of specific neuronal systems. AB - The brains of individuals with dementia due to Alzheimer's disease (AD), Parkinson's disease (PD), and Down's syndrome (DS) exhibit similar neuropathological features, including neuritic plaques, neurofibrillary tangles, and the loss of specific populations of neurons. In addition, these brains show similar transmitter-specific neurochemical alterations. Recent evidence indicates that several pathological and neurochemical changes are related to diseases involving projection systems innervating the telencephalon. At least two transmitter-specific circuits, cholinergic neurons in the basal forebrain and noradrenergic neurons in the locus coeruleus, are selectively affected in many patients with these disorders. This review focuses on these systems because they provide particularly useful examples of the ways in which multidisciplinary studies can provide new clinical-pathological-chemical correlations. Strategies used in these studies are applicable to a wide variety of other neurodegenerative diseases affecting specific populations of neurons. Modern neuropathological approaches to these diseases should eventually allow investigators to directly relate pathogenic processes involving transmitter-specific neuronal populations, whose projections, physiological properties, and functions are known, with the clinical manifestations occurring in human disorders of behavior and cognition. PMID- 2876846 TI - Ocular effects of a relatively selective alpha 2 agonist (UK-14, 304-18) in cats, rabbits and monkeys. AB - UK-14, 304-18 (UK), a relatively selective alpha 2-agonist, was examined for its effects on intraocular pressure (IOP) and pupil diameter (PD) in rabbits, cats and monkeys and on noradrenergic function in the cat nictitating membrane (CNM) preparation. Topical, unilateral administration of UK (0.0005-0.5 mg) produced dose-dependent decreases in IOP and pupil size in normal, unanesthetized rabbits, cats and monkeys. The ocular hypotensive effect of UK in the ipsilateral eye was delayed relative to the contralateral eye in all three species; UK produced an initial transient ocular hypertension in rabbits which was abolished by surgical transection of three major extraocular muscles. Mean arterial blood pressure in rabbits was not affected by 0.005 mg UK topically. The ocular hypotensive and miotic effects of UK were attenuated in superior cervical ganglionectomized (SX) cats and rabbits. Intra-arterially administered UK (0.33, 1.0, 3.3 and 10 micrograms) produced dose-related systemic hypotension and inhibition of contractions of the CNM elicited by electrically stimulating the pre- and postganglionic sympathetic trunks in the urethane/chloralose anesthetized cat. This inhibition was reversed and prevented by 300 micrograms rauwolscine but not by 300 micrograms domperidone. UK also enhanced the contractile response of the CNM to injected norepinephrine (10 micrograms). UK suppressed ocular hypertension induced by water loading and IOP recovery rate following hypertonic saline infusion in rabbits suggesting that aqueous flow was inhibited. These results indicate that UK lowers IOP, in part, by suppressing sympathetic neuronal function which causes a reduction in aqueous flow. PMID- 2876847 TI - Pustular psoriasis: from the wheelchair to the dance floor. PMID- 2876848 TI - European audit of asthma therapy. PMID- 2876849 TI - United States audit of asthma therapy. AB - While variations observed in the approach to treatment among specialists in the United States may be partly related to differences in the types of patients seen, the differences are more likely related to a varied level of awareness among the specialties regarding new concepts of asthma therapy. A heightened awareness in the US of the results of therapeutic interventions often tried in other countries for years prior to their introduction in the US can benefit asthma patients by hastening the adoption of therapeutic advances by physicians in this country. Education of physicians and their patients is essential to improving the quality of life and survival in asthma patients. Physicians must inform patients and their families of the critical importance of prophylactic care and aggressive early intervention at the first sign of an exacerbation in order to once again achieve a declining mortality rate in individuals with asthma. PMID- 2876850 TI - Treatment of bronchial asthma in Japan. PMID- 2876851 TI - Treatment of bronchial asthma in Latin America. PMID- 2876852 TI - Animal model of rabbits for researching epidemic hemorrhagic fever. PMID- 2876853 TI - [Takayasu syndrome in pregnancy: clinical analysis of 20 cases]. PMID- 2876854 TI - [Kinetics of ATP synthesis in incomplete uncoupling indicate the existence of a threshold potential for the functional rearrangement of H+-ATpase]. PMID- 2876855 TI - Presence of a diffusional barrier on metabolite kinetics: enalaprilat as a generated versus preformed metabolite. AB - Studies in the once-through perfused rat liver with the simultaneous delivery of 14 C-enalapril and its polar diacid metabolite, 3H-enalaprilat, revealed different extents of elimination (exclusively by biliary excretion) for the generated (14C-enalaprilat) and preformed (3H-enalaprilat) metabolite (18 and 5% dose) [Pang, Cherry, Terrell, and Ulm: Drug Metab. Dispos. 12, 309-313 (1984)]. The present re-examination of data provided an explanation for these discrepant observations: enalaprilat, being a polar dicarboxylic acid, encounters more of a diffusional barrier than its precursor, enalapril, an ethyl ester of enalaprilat. Programs written in Fortran 77 on mass balance relationships were employed to simulate data upon varying the diffusional clearances for drug (CLd) and metabolite [CLd(mi)] from 1 to 5000 ml/min. The metabolic and biliary intrinsic clearances for drug and metabolite were found by trial and error such that the combinations of all clearance parameters yielded data similar to enalaprilat, and 3H-enalaprilat. Our finding indicated that the diffusional clearance for enalaprilat was low (2 ml/min) compared to that of enalapril (75 ml/min). The presence of a diffusional barrier for enalaprilat retards entry of the preformed metabolite into hepatocytes but prevents efflux of the intracellularly formed generated metabolite into sinusoidal blood, thereby enhancing generated metabolite elimination. PMID- 2876856 TI - The role of carnitine in the conjugation of acidic xenobiotics. AB - Conjugation with carnitine is a major metabolic pathway for cyclopropanecarboxylic acid (CPCA). The CPCA-carnitine is cleaved enzymatically (carnitine acetyltransferase) more slowly in vitro than are acetyl- and propionylcarnitines, but also slightly more extensively. When given orally to a rat, CPCA-carnitine is excreted readily in urine as free CPCA and its glycine conjugate. Effects of dietary exposure of rats to CPCA were determined by feeding cycloprate (a CPCA precursor) at 5000 ppm and then assaying tissue levels of carnitine. Both free and total carnitine in the hearts of female rats were depressed by 39% after 3 weeks at this exaggerated dose. We suggest a possible link between sequestration of carnitine and the observed pathology which includes lipid deposition in the hearts of female rats fed cycloprate at high doses. When a rat was given an oral dose of [14C]benzoic acid, benzoylcarnitine was a minor urinary metabolite (0.04% of applied dose). This result suggests that many other xenobiotic acids may conjugate with carnitine (albeit at low levels) and this role in xenobiotic metabolism may be more general than presently appreciated. PMID- 2876857 TI - Inhibition of glucuronidation and sulfation by dibutyryl cyclic AMP in isolated rat hepatocytes. AB - Dibutyryl cyclic adenosine 3':5'-monophosphate (DBcAMP) has been reported to cause numerous alterations in the activity of hepatic monooxygenase enzymes following in vivo administration or in vitro addition to intact liver preparations. In the present report the effect of the nucleotide on metabolism of p-nitroanisole (pNA) and aniline was studied in isolated rat hepatocytes. Initial studies indicated that in vitro addition of DBcAMP to hepatocytes increased metabolism of both pNA and aniline as determined by the production of oxidized metabolites, p-nitrophenol (pNP) and p-aminophenol, respectively. After enzymatic hydrolysis with beta-glucuronidase and arylsulfatase, it was determined that DBcAMP had increased accumulation of pNP formed from pNA by inhibiting further metabolism via conjugation reactions. Further studies using pNP directly as substrate confirmed the finding and revealed that glucuronidation was more sensitive to the inhibitory effect of DBcAMP than was sulfation. The 8-bromo derivative of cAMP was more potent than DBcAMP at inhibiting glucuronidation, whereas cyclic AMP and dibutyryl cyclic guanosine 3':5'-monophosphate were without effect. Noncyclic adenine nucleotides (ATP, ADP, AMP) also altered pNA and pNP metabolism. ATP and ADP increased pNP accumulation from pNA while ATP and AMP inhibited glucuronidation of pNP. DBcAMP was further found to decrease UDP glucuronic acid levels in a concentration-dependent manner without disrupting the redox state (NAD+/NADH) in hepatocytes. The data suggest that adenine nucleotides exert a nonspecific inhibition upon glucuronidation and sulfation reactions. PMID- 2876858 TI - Metabolism of N,N-diethyl-meta-toluamide by rat liver microsomes. AB - The NADPH- and oxygen-dependent metabolism of N,N-diethyl-m-toluamide (deet insect repellent) has been studied at 37 degrees C in suspensions of liver microsomes from phenobarbital-pretreated male Wistar rats. In pH 8 Tris-HCl buffer and at a substrate concentration of 200 microM, metabolic reactions corresponded to benzylic hydroxylation and N-deethylation, and to combinations of these reactions, leading to N,N-diethyl-m-hydroxymethylbenzamide, N-ethyl-m toluamide, N-ethyl-m-hydroxymethylbenzamide, and m-toluamide. These compounds and N,N-diethyl-m-formylbenzamide were detected in methyl t-butyl ether extracts by capillary gas chromatography using three fused silica columns of different polarities. The structures of the in vitro metabolites were verified by comparisons with samples of authentic standards using combined gas chromatography mass spectrometry. A selective derivatization procedure with acetic anhydride and pyridine facilitated the detection of the two alcohols. The major metabolites, N,N-diethyl-m-hydroxymethylbenzamide and N-ethyl-m-toluamide, were quantitatively determined in derivatized extracts with an internal standard of N,N-dipropyl-m toluamide, a capillary column of DB-1, and a nitrogen-phosphorus detector. The mean enzymatic yield of these two products was 69% in three replicated experiments. PMID- 2876859 TI - Pharmacokinetics, metabolism, and disposition of 6-chloro-2,3,4,5-tetrahydro-3 methyl-1H-3-benzazepine (SK&F 86466) in rats and dogs. AB - The pharmacokinetics and metabolism of 6-chloro-2,3,4,5-tetrahydro-3-methyl-1H-3 benzazepine (SK&F 86466) have been studied in rats and dogs. Using radiolabeled SK&F 86466, it was shown that the compound was completely absorbed from the gastrointestinal tract following oral administration. Most of the administered radioactivity (approximately 80%) was excreted in urine with the remainder excreted in feces via the bile. Very little of the parent compound was excreted unchanged in the urine. The major urinary metabolite, accounting for about 55% of the dose in rat and 35% in dog, was the N-oxide. N-Demethylation also occurs in both species, and in the rat approximately 20% of the dose is metabolized by this route. The plasma concentration vs. time curves following iv administration were analyzed using a two-compartment open model. The distribution phase half-life was 0.24 hr in the rat and 0.37 hr in the dog. In both species the terminal half-life was approximately 2 hr. The volume of distribution at steady state in the rat was 12.1 liters/kg and in the dog was 8.2 liters/kg. About 55% of the drug in plasma was bound to protein in both species so that the volume of distribution of the free drug was 27 liters/kg in the rat and 19 liters/kg in the dog. The clearance of SK&F 86466 from blood was very high in both the dog (56 ml/min/kg) and the rat (191 ml/min/kg). Since less than 1% of the compound was excreted unchanged in urine, the clearance was almost entirely metabolic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876860 TI - The oxidative metabolism of hydralazine by rat liver microsomes. AB - Previous observations have demonstrated a relationship between the toxicity of the antihypertensive drug, hydralazine (HP), and acetylator phenotype, suggesting a role for metabolism in the adverse effects of HP. Experiments were done to characterize the metabolism of HP by rat liver microsomes using a newly developed HPLC assay. HP was metabolized by rat liver microsomes to products identified by HPLC and mass spectroscopy as s-triazolo[3,4-a]phthalazine (TP), 3-methyl-s triazolo[3,4-a]phthalazine (MTP), phthalazine (P), and phthalazinone (PZ). An unknown metabolite was also formed. P, PZ, and the unknown metabolite were established as oxidation products of HP using the model oxidative systems, metal catalyzed autooxidation and horseradish peroxidase. The results of incubations with [14C]HP indicated that P and the unknown metabolite were quantitatively the major metabolites and were produced in similar quantities by rat liver microsomes. The structure of the unknown metabolite based on mass spectral analyses is proposed to be a dimerization product consisting of P and 1 aminophthalazine. Production of all the microsomal metabolites, except TP, required NADPH and decreased when incubations were done with heat-treated microsomes or under an atmosphere of nitrogen or carbon monoxide. Pretreatment of rats with phenobarbital increased the rate of formation of all the metabolites except TP. In contrast, pretreatment with 3-methylcholanthrene or Arochlor 1254 had no effect on P, PZ, TP, or MTP formation and decreased formation of the dimer. Pretreatment with piperonyl butoxide had no effect on the formation of P, PZ, TP, or MTP but decreased formation of the dimer by approximately 50%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876861 TI - Disposition of radiolabeled flumequine in rat and dog. AB - Single doses of 14C-flumequine (a urinary tract antibacterial) were given to rats and dogs. Unchanged drug accounted for more than 80% of the drug in plasma of rats but only 25-50% in plasma of dogs. Although only a small percentage of the dose was excreted in the urine of each species as unchanged drug, a wide differentiation in the urinary metabolite profiles was observed. No significant tissue retention was seen in rats or dogs. PMID- 2876862 TI - An unusual metabolite of testosterone. 17 beta-Hydroxy-4,6-androstadiene-3-one. AB - A testosterone metabolite, 17 beta-hydroxy-4,6-androstadiene-3-one, possessing an absorbance maximum at 284 nm, was formed during incubation of testosterone with liver microsomes from dexamethasone-treated rats. The metabolite was identified by HPLC, UV spectroscopy, and thermospray liquid chromatography/mass spectrometry. The formation of this metabolite by rat liver microsomes required NADPH and oxygen and was inhibited markedly by SKF 525-A, 2,4-dichloro-6 phenylphenoxyethylamine, or CO/O2 (8:2, v/v), but not by cyanide, an inhibitor for stearyl-CoA desaturase. Pretreatment of rats with phenobarbital, pregnenolone 16 alpha-carbonitrile, and dexamethasone enhanced the formation of this metabolite in parallel with the increase in formation of 6 beta hydroxytestosterone (r2 = 0.99). Although 16-methylprogesterone, a known 6 beta hydroxylase inhibitor, competitively inhibited the formation of the metabolite and 6 beta-hydroxytestosterone by liver microsomes from dexamethasone-treated rats, the metabolite was not formed from either 6 beta-hydroxytestosterone or 7 hydroxytestosterone during incubation with liver microsomes. These findings are consistent with the view that cytochrome P-450 isozymes that catalyze 6 beta hydroxylation of steroids in rat liver microsomes also catalyze the dehydrogenation of testosterone to form a double bond between the C-6 and C-7 positions. PMID- 2876864 TI - Isolation and characterization of N-methyl-N'-oxonicotinium ion, a new urinary metabolite of R-(+)-nicotine in the guinea pig. AB - Biotransformation of both R-(+)-nicotine and R-(+)-N-methyl-nicotinium acetate in male Hartley guinea pigs affords a new quaternary amine metabolite, which was isolated and purified from urine by preparative HPLC. The structural analysis of the metabolite was carried out using UV spectrophotometry, direct thermospray mass spectrometry, and Fourier transform 1H-NMR spectroscopy. The structure of the metabolite was confirmed by synthesis and shown to be a mixture of the cis 1'S,2'R-, and trans-1'R,2'R-diastereomers of N-methyl-N'-oxonicotinium ion, formed in the ratio 1.6:1.0, respectively. S-(-)-Nicotine under similar conditions does not undergo this biotransformation. PMID- 2876863 TI - The role of acetylator genotype on hepatic and extrahepatic acetylation, deacetylation, and sulfation of 2-aminofluorene, 2-acetylaminofluorene, and N hydroxy-2-acetylaminofluorene in the inbred hamster. AB - In vitro rates of acetylation, deacetylation, and sulfation were measured with carcinogenic arylamine, arylamide, and arylhydroxamic acid substrates using enzyme preparations derived from inbred hamster tissues of known acetylator genotype. Homozygous rapid acetylators (Bio. 87.20), heterozygous acetylators (Bio. 87.20 X Bio. 82.72/H F1), and homozygous slow acetylators (Bio. 82.73/H) did not differ significantly with respect to paraoxon-resistant intermolecular N,N-transacetylation reactions from N-hydroxy-2-acetylaminofluorene to 4 aminoazobenzene in tissue cytosol. Similarly, they did not differ with respect to paraoxon-sensitive, microsomal N-hydroxy-2-acetylaminofluorene and 2 acetylaminofluorene deacetylase, and cytosolic N-hydroxy-2-acetylaminofluorene sulfotransferase activity. However, a gene dose-response relationship was observed in the same animals for cytosolic acetyl coenzyme A-dependent 2 aminofluorene N-acetyltransferase activity. Partial purification of liver cytosol yielded two paraoxon-resistant isozyme forms of acetyltransferase activity. The rates of one isozyme were acetylator genotype dependent (polymorphic), whereas the rates of the second isozyme appeared to be acetylator genotype independent (monomorphic). Acetyl coenzyme A-dependent 2-aminofluorene N-acetyltransferase activity was catalyzed at high rates by both isozymes, whereas transacetylation of 4-aminoazobenzene by various acyl donors (N-hydroxy-2-acetylaminofluorene, N hydroxy-4-acetylaminobiphenyl, and acetyl coenzyme A) was catalyzed primarily (but not exclusively) by the monomorphic acetyltransferase isozyme. These results provide further information concerning the importance of acetylator genotype in the metabolism of carcinogenic arylamines and their metabolites. PMID- 2876865 TI - Effect of cimetidine or ranitidine pretreatment on hepatic mixed function oxidase activity in the rat. AB - This study compared the effect of single equimolar oral doses of cimetidine (100 mg/kg) or ranitidine (139 mg/kg) on rat hepatic mixed function oxidases. Cimetidine significantly (p less than 0.05) increased hexobarbital sleeping time and prolonged aminopyrine and theophylline elimination. In contrast, ranitidine did not significantly affect hexobarbital sleeping time and theophylline elimination but significantly (p less than 0.025) increased aminopyrine elimination. Aminopyrine N-demethylase activity in vitro was significantly (p less than 0.05) inhibited by cimetidine pretreatment but significantly (p less than 0.025) increased by ranitidine pretreatment. The direct addition of cimetidine or SKF 525A to the 10,000g supernatant fraction from controlled liver homogenates decreased aminopyrine N-demethylase activity, whereas the direct addition of ranitidine tended to increase aminopyrine N-demethylase activity. A significant correlation (r = 0.65, p less than or equal to 0.005) was observed between hexobarbital sleeping time in vivo and aminopyrine N-demethylase activity in vitro in the same rat. The results of this study showed that cimetidine inhibited mixed function oxidases, whereas ranitidine had no effect or tended to stimulate mixed function oxidases. PMID- 2876866 TI - Normal levels of hepatic drug-metabolizing enzymes in neonatally induced, growth hormone-deficient adult male and female rats. AB - The effects of chronic growth hormone deficiency on the growth hormone-dependent, sexually dimorphic hepatic drug-metabolizing enzymes were studied in adult rats of both sexes. Neonatal administration of monosodium L-glutamate produced the expected syndrome characterized by stunted growth, obesity, prolonged vaginal estrus, and an inhibition in the growth of the pituitaries, adrenals, gonads, sexual accessory organs, and kidneys. Associated with these abnormalities was a 90% reduction in the concentration of serum growth hormone in male and female rats. In contrast, the activities of hepatic aniline hydroxylase, total cytochrome P-450, and the Michaelis constants and maximal velocities for hexobarbital hydroxylase and UDP-glucuronosyltransferase were unaffected by the profound deficiency in growth hormone. PMID- 2876867 TI - Metabolic disposition of ivermectin in tissues of cattle, sheep, and rats. AB - The metabolic disposition of ivermectin, a new antiparasitic drug, has been studied in cattle, sheep, and also in rats dosed with the drug labeled with tritium in the C-22,23 positions. In the edible tissues of these animals, the unaltered drug was the major tissue residue component and was quantitated by HPLC reverse isotope dilution assay. The depletion half-lives of the drug ranged between 1 and 6 days, similar to those of the total tissue residue in these species. Most metabolites present in the liver tissues were more polar than the parent drug. Based on spectral (NMR, mass spectrometric) analysis and chromatographic comparison with authentic compounds prepared by in vitro rat or steer microsomal incubations, three of these metabolites have been isolated and identified as the hydroxylation derivatives of ivermectin, i.e. 24-hydroxymethyl H2B1a, its monosaccharide, and 24-hydroxymethyl-H2B1b. PMID- 2876869 TI - Biotransformation and quantitative determination of sulfur-containing metabolites of 1,4-dibromobutane in the rat. AB - Two stable sulfur-containing metabolites were isolated from rat urine following administration of the mutagenic 1,4-dibromobutane. They were identified as tetrahydrothiophene and 3-hydroxysulfolane by gas chromatography and gas chromatography-mass spectrometry and were found to be excreted in 48-hr urine, representing 5.8 +/- 1.1 and 57 +/- 15% of the dose of 1,4-dibromobutane, respectively. When urines of rats treated with 1,4-dibromobutane were collected in a buffer of pH 1.0, however, only 3-hydroxysulfolane was found. It was indirectly shown that an N-acetyl-S-(beta-alanyl)tetrahydrothiophenium salt was present in urine and that this metabolite is probably the precursor of tetrahydrothiophene. The latter product is only formed at higher pH values and quantified after addition of NaOH to buffered urines. Tetrahydrothiophene is probably also formed under physiological conditions in vivo from the N-acetyl-S (beta-alanyl)-tetrahydrothiophenium salt, but in this case it is subsequently transformed to 3-hydroxysulfolane. Based on these findings, a biotransformation scheme of 1,4-dibromobutane in the rat is proposed. The extensive metabolism via glutathione conjugation resulted in efficient detoxification of 1,4 dibromobutane. PMID- 2876868 TI - Biotransformation of 1,2-dibromopropane in rats into four mercapturic acid derivatives. AB - 1,2-Dibromopropane was administered orally in doses of 50-350 mg/kg to male Wistar rats. Four mercapturic acids were identified in urine by GC/MS, viz. N acetyl-S-(2-oxopropyl)-L-cysteine (I), N-acetyl-S-(2-hydroxypropyl)-L-cysteine (II), N-acetyl-S-(1-carboxyethyl)-L-cysteine (III), and N-acetyl-S-(2-bromo-2 propenyl)-L-cysteine (IV). Mercapturic acid IV was a minor metabolite which could only be measured at doses of 200 mg/kg or higher. In 24 hr, urinary excretion of mercapturic acids amounted to about 36% of the dose (11% I, 21% II, 4% III, 0.2% IV). No dose dependency was found up to the highest dose. A unified scheme is proposed for the metabolism of 1,2-dibromopropane in the rat, which accounts for the identified mercapturic acids. The role of direct glutathione conjugation in the route leading to the major metabolite II, presumably involving thiiranium ion formation, is discussed. This route probably is biologically not very important because of the absence of detectable activity of 1,2-dibromopropane toward glutathione S-transferases in vitro, the very low mutagenicity of 1,2 dibromopropane, and the high mutagenic activity of N-acetyl-S-(2-bromopropyl)-L cysteine methyl ester which was studied as a model compound for direct conjugation. PMID- 2876870 TI - Biotransformation of felodipine in liver microsomes from rat, dog, and man. AB - The biotransformation of the calcium antagonist felodipine was investigated in liver microsomes from rat, dog, and man. The metabolites were quantified and identified by gradient elution reverse phase liquid chromatography, liquid scintillation analysis, and GC/MS. Ten metabolites were identified, including the pyridine analogue of felodipine, two carboxylic mono acids, two ester lactones, as well as the corresponding open hydroxy acid forms, and a lactonic compound with a carboxylic acid group. The presence of two decarboxylated products was also verified. Metabolites with an intact dihydropyridine nucleus were not detected. The total pool of metabolites formed in vitro was more lipophilic than that excreted in urine from the same species. The metabolic pathways were similar in the three species studied, although quantitative differences were observed. Comparison between incubations with liver microsomes from male and female rats indicated that the females metabolized felodipine more slowly than the males. From a more detailed quantitative analysis of eight metabolites, in relation to incubation time, it was apparent that the hydroxylation of the 2- and 6-methyl groups occurred at a faster rate (0.027 min-1) than did the ester hydrolysis (0.016 min-1). These hydroxy metabolites rearranged spontaneously to lactones. The results from this study indicate that the open hydroxy acid metabolites were formed enzymatically from the corresponding lactones. A metabolic scheme for the overall metabolism of felodipine is given and discussed with reference to the in vivo situation. PMID- 2876871 TI - Product enantioselectivity in the N-glucosylation of amobarbital. PMID- 2876872 TI - Active tubular secretion of 1-naphthyl-beta-D-glucuronide in the isolated perfused rat kidney. PMID- 2876873 TI - Aminopyrine pharmacokinetics in the rat may depend on hepatic blood flow. PMID- 2876874 TI - Comparison of H1-antihistamines for pruritus in end-stage renal disease. PMID- 2876875 TI - [Prevention of stress bleeding--do we need a new concept?]. PMID- 2876876 TI - [Treatment of chronic glaucoma]. PMID- 2876877 TI - [Current possibilities of cerebrospinal fluid studies in neurologic diagnosis]. PMID- 2876878 TI - The effect of a hypertensive drug on tongue and major salivary glands. PMID- 2876879 TI - Short-term double-blind trial of pipothiazine palmitate and haloperidol in the acute phase of schizophrenia. AB - A 22-day double-blind study of 53 acutely ill, recently admitted schizophrenic patients aged 18-45 years is described. Twenty-seven patients received 20 mg of haloperidol i.m. on the first day and 200 drops of haloperidol (20 mg) p.o. in a single dose in a glass of milk with grenadine, daily at 8:00 A.M. from the 2nd to the 21st day. Twenty-six other patients received 100 mg of pipothiazine palmitate i.m. on the first day and a glass of milk with grenadine daily at 8:00 A.M. from the 2nd to the 21st day. The two groups responded similarly to the drugs as indicated by both BPRS scores and CGI ratings. Extrapyramidal side effects were not significantly different for the two groups. Although a single injection of pipothiazine palmitate was as effective as the daily administration of haloperidol in a 22-day study of recently admitted schizophrenic patients, in the acute phase, a general recommendation for the use of long-acting neuroleptics cannot be made because more information on side effects is needed and a larger number of patients must be studied. However, long-lasting neuroleptics can be recommended for special situations such as when the patient is severely disturbed and/or refuses treatment. PMID- 2876880 TI - [Reduced waiting capacities as a possible mechanism of action of benzodiazepines. A hypothesis derived from their behavioral effects in animals]. AB - In classical punishment procedures, suppression of responding which allows the animal to avoid electric foot-shock is attenuated by benzodiazepines (BZD). Such a release of responding is interpreted as a reflection of the anxiolytic activity of BZD. In these situations however, behavioral suppression also delays the obtention of the food-reward. Therefore, shock-mediated waiting could be as critical a target as shock-induced fear for BZD in punishment procedures. The present study was designed to investigate whether BZD are effective in reducing the capacity of animals to wait for an expected food reward. Fasted rats trained in a T-maze were allowed to choose between two magnitudes of reward: immediate but small (2 pellets) vs delayed but large (8 pellets). Diazepam (2-4 mg/kg), nitrazepam (2 mg/kg), chlordiazepoxide (16 mg/kg) or clobazam (16 mg/kg) decreased the number of times the large reward was chosen by rats subjected to a waiting period of 15 s before having access to the large reward. In conflict situations, rats trained to press a level for food reward were given both 1 pellet and 1 electric foot-shock for pressing during punished periods of fixed duration signalled by a warning stimulus. The diazepam (2 mg/kg)-induced increase in the number of punished presses (anti-punishment effect) was closely related to the percent punishment time within a session. The release of punished responding reached a statistically significant level only when the total punishment-time accounted for at least 40% of the total duration of the session.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876881 TI - Internalization and subcellular distribution of radiolabeled somatostatin-28 in mouse anterior pituitary tumor cells. AB - The ACTH-secreting mouse AtT-20/D16-16 (AtT-20) tumor corticotroph possesses receptors for the tetradecapeptide somatostatin (S-14) to which the 14-amino acid N-terminal extension somatostatin-28 (S-28) also binds. When AtT-20 cells are exposed to either S-14 or S-28 for extended periods of time, a marked decrease in S-14 receptor density is observed. Since receptor down-regulation is frequently associated with internalization of ligand and/or receptor, the present study was designed to establish whether AtT-20 cells could in fact internalize S-28 and to determine the subcellular localization of internalized peptide. Cells were incubated in the presence of [Leu8, D-Trp22,125I-Tyr25] S-28 for 1, 4, and 18 h; washed with PBS; and harvested. Cell pellets were fixed, sectioned, and analyzed by light and electron microscopic autoradiography. Uptake of radiolabeled S-28 (90% of all cells) was inhibited by 80% when unlabeled S-14 was coincubated with [125I]S-28. Of the cell compartments examined, plasma membrane, secretory granules, lysosomes, Golgi apparatus, and nuclear membrane all had distinct time dependent labeling patterns. Plasma membranes were maximally labeled 1 h after exposure to [125 I] S-28. Secretory granule and lysosomal labeling was observed within 1 h, but was maximal after 18 h of exposure. Labeling of the granule compartment preceded that of the Golgi apparatus. The nuclear compartment (membranes plus nuclei) was also labeled significantly after 18 h of incubation. However, the nuclear membrane itself was labeled after only 1 h of exposure to the ligand. The data suggest that radiolabel is transferred from the plasma membrane to the intracellular organelles as a function of exposure time. Labeling of the secretory compartment suggests that granules may bind and protect internalized peptide from lysosomal degradation. Appearance of label in the nuclear compartment suggests that S-28 (and S-14) may have effects on transcriptional activity in AtT-20 cells. PMID- 2876882 TI - Effect of somatostatin withdrawal and growth hormone (GH)-releasing factor on GH release in vitro: amount available for release after disinhibition. AB - The secretion of GH is strikingly episodic. We have suggested that the timing of the episodic bursts of GH secretion is set by somatostatin (SRIF) withdrawal, whereas the magnitude of the bursts is determined by the amount of GH-releasing factor (GRF) impinging on the somatotrophs before and during SRIF withdrawal. We have now used an in vitro model of perifused rat pars distalis cells to examine the interaction of SRIF and GRF on GH release and, in particular, to examine the effect of GRF on the magnitude of the burst of GH release that follows SRIF withdrawal. After 30 min of perifusion with SRIF (10(-9) M), there follows an immediate but small burst of GH release. The burst of GH release following concurrent perifusion with SRIF plus GRF (10(-10) M) is increased, with a 7.5- to 9.5-fold increase in the peak secretion rate. When GRF is maintained after the withdrawal of SRIF, the peak secretion rate is not different from that seen after simple withdrawal of both SRIF and GRF, but the duration of the burst is increased. These data demonstrate that the presence of GRF during SRIF perifusion, while not altering basal release, does strikingly increase the post SRIF release of GH. We propose that a similar relation applies in vivo, where SRIF withdrawal sets the timing of the episodic bursts of GH release, whereas GRF determines the magnitude. PMID- 2876883 TI - Intratesticular factors and testosterone secretion: the role of luteinizing hormone in relation to changes during puberty and experimental cryptorchidism. AB - Testicular interstitial fluid (IF) from the rat contains a nongonadotropic polypeptide factor (or factors) which can enhance human CG (hCG)-stimulated testosterone production by Percoll-purified Leydig cells in vitro. The potential importance of this factor has been investigated by measuring its effective levels in testicular IF from individual rats during sexual maturation or after the induction of unilateral cryptorchidism (UCD). In both situations, the effect of modulating LH drive to the testis was also assessed. In abdominal testes from UCD rats, levels of the IF factor were nearly doubled (P less than 0.001) when compared to levels in the contralateral scrotal testis; this was associated with more than an 85% reduction in IF testosterone levels. Further lowering of testosterone levels by the injection of an antiserum to LH beta, raised levels of the IF factor by 30-40% (P less than 0.01) in both scrotal and abdominal testes. Conversely, raising of testosterone levels by injection of hCG caused more than a 90% reduction (P less than 0.001) in levels of the IF factor in both scrotal and abdominal testes. During sexual maturation, levels of the IF factor doubled (P less than 0.01) between 30 and 40 days of age, remained high until 70 days of age, and then decreased to the lower levels found in adult rats. High pubertal levels of the IF factor were associated with the most rapid phase of testicular growth and with a steady increase in the IF levels of testosterone. Injection of pubertal or adult rats with antiserum to ovine LH (oLH) reduced testosterone levels by approximately 85% and doubled (P less than 0.01) levels of the IF factor(s) in both groups. It is concluded that levels of the IF-factor are influenced: by testosterone levels and/or LH drive and by the maturational and/or functional status of the testis. These results also suggest that changing levels of the IF factor may be of physiological significance during puberty. PMID- 2876884 TI - Human growth hormone (GH)-releasing factor stimulates and somatostatin inhibits the release of rat GH variants. AB - Two-dimensional polyacrylamide gel electrophoresis (2D PAGE) was used for the analysis of proteins secreted by male rat pituitary cells in monolayer culture in the presence of 10 nM human GH-releasing factor (hGRF) or 30 nM somatostatin (SRIF) or in the absence of these factors. More than 300 medium proteins were reproducibly detected either by fluorographic autoradiography or by silver staining. Immunoreactivity of each protein was examined after 2D PAGE followed by Western blotting and immunostaining with affinity-purified antirat GH (rGH) antibody. While there was a cluster of immunoreactive spots in the GH dimer range (40,000-50,000 mol wt), at least 16 medium proteins of mol wt 22,000 or less were also stained. Among these 16 proteins the release of 15 was stimulated and the release of 14 was inhibited by hGRF and SRIF, respectively. On the other hand, there were 3 proteins of approximate mol wt 16,000 whose secretion was regulated in a coordinate manner as rGH by the hypothalamic factors but which did not cross react with anti-rGH antibodies. The increase or decrease in the radioactivity of each protein spot obtained from media after pituitary cells were incubated with [35S]methionine and hypothalamic factors was analyzed statistically. A pulse chase study suggested that at least 7 of the hormonally regulated proteins, including rGH, were synthesized very rapidly. Finally, the 2D PAGE analysis of cell-free translation products of messenger RNA derived from male rat anterior pituitaries revealed the presence of about 40 rGH-immunoreactive proteins which included pre-GH. These data suggest that there are multiple forms of rGH-variants or rGH-related proteins. The biological significance(s) of all the rGH immunoreactive proteins and of the GRF- and SRIF-regulated pituitary proteins remains unclear. It is evident that a number of these proteins are synthesized and released rapidly by pituitary cells in culture. Furthermore, the presence of multiple genes for these rGH-related proteins is suggested by the large family of immunoreactive gene products identified after cell-free translation of messenger RNA derived from the pituitary. PMID- 2876885 TI - Cytochemical studies of corticotropin-releasing factor (CRF) receptors in anterior lobe corticotropes: binding, glucocorticoid regulation, and endocytosis of [biotinyl-Ser1]CRF. AB - A new synthetic biotinylated N-terminal analog of CRF was used to study its binding, endocytosis, and route of processing. The new analog was fully bioactive compared to rat(r) CRF in an ACTH bioassay and pituitary membrane receptor assay. In 1- to 4-day cultured pituitary cell monolayers, CRF receptors were labeled for 1-biotinylated rCRF (1-bio-CRF) and demonstrated with avidin-fluorescein (Ar-Fl) in living cells or with avidin-biotin-peroxidase complex (ABC) in fixed cells. The percentages of fluorescein-labeled cells were comparable to those stained with the ABC technique. The specificity of binding by 1-bio-CRF was shown by the ability of unlabeled CRF to inhibit staining, whereas 100 nM arginine vasopressin, angiotensin II, or somatostatin was without effect. Treatment of the cells with 100 nM glucocorticoids for 1 or 24 h before the 3-min stimulation with 1-bio-CRF caused a 50-60% reduction in the percentage of cells stained with either ABC or Av-Fl. Pretreatment with vehicle, a lower dose of corticosterone (10 nM), or other steroids (dihydrotestosterone or epitestosterone) did not decrease the percentage of cells stained with the ABC technique. The lower dose of glucocorticoids decreased the stain with Av-Fl by 50% after 1 h of pretreatment. Electron microscopic analysis of binding and endocytosis of 1-bio CRF stained with the ABC technique showed patches of stain on coated pits and microvilli during the first 3 min of exposure. Internalization in vesicles and receptosomes was also seen during the first 3 min. Some stain was found on secretion granules as early as 1 min after exposure. Five minutes after exposure, the stain was in receptosomes, Golgi cisternae, condensing vesicles in the transreticular Golgi region, and 23% of the granules in the cytoplasm. During the later exposure periods (15-30 min), stain was also seen in multivesicular bodies. The correlative light and electron microscopic studies showed that 1-bio-CRF is rapidly internalized after patching on the surface and is ultimately found in multivesicular bodies or granules. We postulate that these structures are involved in processing or degradation of the ligand. PMID- 2876886 TI - Influence of sex steroid hormones on rat growth hormone-releasing factor and somatostatin in dispersed pituitary cells. AB - The modulatory effects of glucocorticoid and sex steroid hormones on the effects of rat GH-releasing factor (GRF) and somatostatin (SRIF) on GH release and biosynthesis were studied in monolayer cultures of rat anterior pituitary cells with RIA and quantitative immunoprecipitation methods. Dexamethasone (10(-7) M), a potent synthetic glucocorticoid, increased both the sensitivity and maximum response of GH release stimulated by GRF. Progesterone (10(-7) M) also enhanced GH release stimulated by GRF. The stimulatory effects of dexamethasone and progesterone were dose dependent and required a latent period of at least 24 h to be evident. Testosterone, dihydrotestosterone, and 17 beta-estradiol showed no apparent influence on GRF-induced GH release under the same conditions. None of the hormones studied showed significant influences on basal or SRIF-suppressed GH release. Progesterone added to the maximally effective concentrations of dexamethasone had no additional effects on GRF-induced GH release. The effect of progesterone was attenuated by both 5 alpha-dihydronorethindrone, a progesterone antagonist and 17 alpha-methyltestosterone, a glucocorticoid antagonist. In terms of GH synthesis, stimulatory effects of GRF on GH synthesis were apparent only when pituitary cells were pretreated with dexamethasone. These results indicate that: pretreatment with glucocorticoid or progesterone enhances the effects of GRF on GH release and/or synthesis; these two steroids share at least one common step to enhance GRF effects; and steroid hormones have little influence on basal or SRIF-suppressed GH release. PMID- 2876887 TI - Quantitative in vivo autoradiographic localization of [125I-Tyr11]somatostatin-14 and [Leu8,D-Trp22-125I-Tyr25]somatostatin-28-binding sites in rat brain. AB - Quantitative in vivo autoradiography was used to identify and compare the regional distribution of specific binding sites for blood-borne [125I Tyr11]somatostatin-14 (S-14 section) and [Leu8,D-Trp22-125I-Tyr25]somatostatin-28 (S-28 section) in the rat brain. Rats were given intracardiac injections of 17 pmol S-14 section (with or without unlabeled S-14) or 17 pmol S-28 section (with or without unlabeled S-28). After whole body perfusion and fixation, brains were processed for light microscopic autoradiography of S-14 section- and S-28 section binding sites. Of the peripheral tissues, the adrenal glands showed the highest uptake of S-14 section and S-28 section (determined by counting) and were subsequently processed for autoradiography for comparison with brain. Specific autoradiographic grains (ARG) associated with both radioligands were identified only in the circumventricular organs (CVOs). The highest ARG density associated with S-14 section was found in the area postrema, followed in decreasing order by the subfornical organ and the organum vasculosum lamina terminalis region. Median eminence (ME) contained virtually no specific S-14 section ARG. As with S-14 section, the highest ARG density of S-28 section-binding sites was also found in the area postrema, which labeled approximately equally with the two radioligands. This was followed by the ME, subfornical organ, and organum vasculosum lamina terminalis. The overall patterns of labeling of the CVOs with S-14 section and S 28 section showed significant differences, especially in the ME. Within the ME, labeled S-28 section was concentrated in a broad band throughout the external zone in a location identical to that of immunoreactive S-14. Analysis of dose response curves obtained with 0.3-30 nmol unlabeled S-14 or S-28 revealed IC50 values for S-14 3- to 6-fold lower than those for S-28 for all labeled CVOs. With both S-14 section and S-28 section, the labelling density of the adrenal glands was double that of the area postrema. Adrenal binding of the radioligands was confined to the cells of the zona glomerulosa. We conclude: specific high affinity binding sites for S-14 section and S-28 section exist in the CVOs and the adrenal glomerulosa; and the 3- to 6-fold higher affinity of binding of S-14 to CVOs compared to S-28 together with the dissimilar patterns of labelling of the different CVOs by the two radioligands suggest the existence of separate populations of S-14 and S-28 receptors. PMID- 2876889 TI - Case of equine cryptorchidism resulting from persistence of the suspensory ligament of the gonad. PMID- 2876888 TI - Response of rat pituitary anterior lobe prodynorphin products to changes in gonadal steroid environment. AB - The total content of rat pituitary anterior lobe (AL) immunoreactive (ir) dynorphin A (ir-Dyn A) and ir-dynorphin B (Dyn B) increased in male rats between 15 and 58 days of age, but there was little alteration in the concentration of ir Dyn A or B expressed relative to protein content. Adult rats (90 days of age) had lower concentrations of these peptide immunoreactivities in the AL. Castration of 58-day-old male rats produced a testosterone-reversible loss of ir-Dyn A and B by 50-60% 3 days after surgery. Thereafter, the levels of these peptides gradually increased to 2.5 times the levels found in control animals at 1 month after castration. These effects of castration on AL dynorphin were not seen in 15-day old rats and were much less marked in adults. Similar changes were seen in the levels of other prodynorphin products, alpha- and beta-neo-endorphin (ir-alpha nEnd and ir-beta-nEnd), and ir-[Leu5]enkephalin (ir-LE). Administration of testosterone (100 micrograms/100 g BW) to castrated rats for 2 days largely prevented the drop in the levels of AL ir-Dyn A and B. Ovariectomy produced an increase in the levels of ir-Dyn A, Dyn B, alpha-nEnd, beta-nEnd, and LE 2 weeks after surgery, but, in contrast to castration, no significant decrease was seen 3 days after ovariectomy. These changes in AL content of dynorphin-related peptides after castration or ovariectomy directly reflect those previously reported for AL content of LH. The mechanisms regulating storage (and perhaps secretion) of AL peptides derived from prodynorphin may be similar to those regulating storage and secretion of LH and FSH in rat AL. AL ir-LE could potentially arise from proenkephalin A or prodynorphin (proenkephalin B). Ir-LE levels in AL were approximately 10 times higher than the levels of ir-[Met5]-enkephalinyl-Arg-Gly Leu (ME-RGL) in male rat AL, and changes in ir-LE content after castration were very similar to those observed in other prodynorphin-derived peptides, but different from the effects of castration on ir-ME-RGL. It is possible that prodynorphin is a major source of AL ir-LE. PMID- 2876890 TI - ATP synthase complex from beef heart mitochondria. Separation of protein bands in the region of 28-31 kDa. AB - ATPase/ATP synthase preparations originally contain protein bands in the 28-31 kDa region. The present study demonstrates separation of the band at 29 kDa (adenine nucleotide translocator) from a band at approximately 31 kDa. In cholate/ammonium sulfate-extracted ATP synthases removal of the 31-kDa band results in decrease of ATP-Pi exchange and oligomycin sensitivity of the ATPase activity. It is suggested that the protein band at 31 kDa is heterogeneous, containing diverse activities, the identities of which are yet to be determined. PMID- 2876891 TI - Conformational interactions between alpha and beta subunits in the F1 ATPase of Escherichia coli as shown by chemical modification of uncA401 and uncD412 mutant enzymes. AB - In contrast to wild-type F1 adenosine triphosphatase, the beta subunits of soluble ATPase from Escherichia coli mutant strains AN120 (uncA401) and AN939 (uncD412) were not labeled by the fluorescent thiol-specific reagents 5 iodoacetamidofluorescein, 2-(4'-iodoacetamidoanilino)naphthalene-6-sulfonic acid or 4-[N-(iodoacetoxy)ethyl-N-methyl]amino-7-nitrobenzo-2-oxa-1,3-diazole. The mutation in the alpha subunit (uncA401) of F1 ATPase thus influences the accessibility of the single cysteinyl residue in the beta subunit. Following reaction of ATPase with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole or N,N' dicyclohexylcarbodiimide, the alpha and beta subunits of the uncA401, but not of the uncD412 mutant F1 ATPase were intensely labeled by a fluorescent thiol reagent. The mutation in the beta subunit (uncD412) thus influences the accessibility of the cysteinyl residues in the alpha subunit. In other work [Stan Lotter, H. and Bragg, P.D. (1986) Arch. Biochem. Biophys. 248] we have shown that 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole and 2-(4' iodoacetamidoanilino)naphthalene-6-sulfonic acid react with a different beta subunit from that labeled by N,N'-dicyclohexylcarbodiimide. This asymmetry with respect to modification by 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole and N,N' dicyclohexylcarbodiimide was seen in both mutant enzymes. In addition, the modification of one beta subunit of the uncA401 F1 ATPase induced the previously unreactive sulfhydryl group of another beta subunit to react with 2-(4' iodoacetamidoanilino-naphthalene-6-sulfonic acid. These results provide evidence for at least three types of conformational interactions of the major subunits of F1 ATPase: from alpha to beta, from beta to alpha, and from beta to beta. As in wild-type ATPase, labeling of membrane-bound unc mutant ATPase by a fluorescent thiol reagent modified the alpha subunits. This suggests that a conformational change of yet a different type occurs when the enzyme binds to the membrane. PMID- 2876892 TI - Nucleotide sequence of the structural gene for dihydroorotase of Escherichia coli K12. AB - The nucleotide sequence of the dihydroorotase structural gene, pyrC, of Escherichia coli K12 has been determined. The DNA sequence predicts a polypeptide chain of 347 amino acid residues corresponding in size and composition to the previously purified dihydroorotase subunit. Nuclease S1 mapping indicated that transcription of pyrC is initiated around 40 base pairs upstream from the translational start. The transcriptional leader region contains a region of dyad symmetry, which allows a stable hairpin to be formed. This sequence may have regulatory functions since similar structures are found in other pyr genes. The nucleotide sequence also contains a 186-codon open reading frame in front of pyrC. Nuclease Bal31-deletion derivatives of pyrC plasmids indicate that this gene does not affect the expression of pyrC. The predicted polypeptide chain shows a putative signal sequence. Downstream from the structural gene a sequence similar to a rho-independent transcriptional terminator is found. This unknown gene may thus encode a membrane protein of unknown function. PMID- 2876893 TI - Intravenous digital subtraction angiography in Takayasu's disease. A report of 32 cases. AB - IVDSA appears to be a reliable method and should therefore be considered as a first step examination when Takayasu's disease is suspected. The simplicity and safety of the method provide a rationale for the use of this technique in Takayasu's disease. Therapeutic decisions can usually be obtained without further radiological investigation, and conventional arteriography has to be performed only when data obtained with IVDSA are insufficient. In these rare cases, conventional arteriography aims at the investigation of a particular area. The site of arterial puncture can be precisely guided by IVDSA. PMID- 2876894 TI - Short-term haemodynamic effects of dopexamine in patients with chronic congestive heart failure. AB - Dopexamine (FPL 60278) is a new dopamine analogue which possesses a combination of dopamine receptor and beta-2-adrenoreceptor agonist properties. The aim of our study was to evaluate the short-term haemodynamic effects of dopexamine administered by intravenous infusion at different dosage rates. Eight patients with chronic congestive heart failure were studied. A dose of 1 microgram kg-1 min-1 produced a 27% decrease in systemic vascular resistance index (32.6 to 23.9 res. units m2, P less than 0.001 and a significant increase in cardiac index (2.7 to 3.6 l min-1 m-2, P less than 0.001). Stroke volume index and heart rate increased significantly by 22% and 7%, respectively. An increase in left ventricular stroke work index was also seen at the dose level inducing the maximum cardiac output. Left ventricular filling pressures and arterial blood pressures were not affected. We conclude that administration of dopexamine to patients with congestive heart failure augments cardiac performance at rest. PMID- 2876895 TI - Altered plasma concentrations of glutamate, alanine and citrate in the early phase of acute myocardial infarction in man. AB - Plasma levels of glutamate, alanine, free fatty acids (FFA), citrate, glucose, insulin, lactate, creatine kinase and aspartate aminotransferase were determined frequently during the first 2-48 h after onset of chest pain in 10 patients who developed acute myocardial infarction (AMI) and in 8 who did not (non-AMI). An initial decrease in plasma glutamate and increase in alanine was found in AMI compared to non-AMI patients. The AMI group showed early, moderate rises of plasma FFA and citrate concentrations, positively related to the initial ST segment elevation and to the enzymatic estimated infarct size. The AMI patients were continuously hyperglycaemic, but their relative insulin response i.e. plasma glucose/insulin ratio was identical to that of non-AMI patients. Lactate values did not differ between the two groups. Via participation in the malate-aspartate shuttle and by shunting pyruvate to alanine instead of lactate, glutamate is of importance for maintaining myocardial glucose utilization. Our finding of initial low plasma glutamate concentrations after onset of myocardial infarction suggests insufficient glutamate supply to the ischaemic myocardium. On basis of this and animal experiments, an external supply of glutamate might be a 'metabolic' treatment of AMI, alternative or additional to glucose-insulin-potassium infusion in order to promote myocardial glucose oxidation. PMID- 2876897 TI - Hypogammaglobulinaemia and malakoplakia: response to bethanechol. AB - A second patient is described with the syndrome of hypogammaglobulinaemia and malakoplakia; he too responded dramatically to bethanechol treatment and remains well on it. PMID- 2876896 TI - Evaluation of 75Br-labelled butyrophenone neuroleptics for imaging cerebral dopaminergic receptor areas using positron emission tomography. AB - A comparative evaluation of three radiobrominated butyrophenone neuroleptics- bromospiperone (BSP), brombenperidol (BBP), and bromperidol (BP)--was made to assess the applicability of these compounds as radiopharmaceuticals labelled with the positron emitter 75Br (T1/2 = 1.6 h) for mapping cerebral dopaminergic receptor areas non-invasively with positron emission tomography (PET). BSP, BBP, and BP were prepared in high specific activities with high radiochemical yields, using electrophilic reactions with no-carrier-added 77Br- or 75Br-. Screening tests in rats using 77Br-labelled compounds indicated D2-specific localization for 77Br-BSP and 77Br-BBP, whereas PET experiments in baboons showed that only 75Br-BSP preferentially localized in cerebral tissues rich in dopaminergic receptors. The data suggest an inverse relationship between cerebral uptake and receptor-specific localization, which was attributed to a complicated interplay between the D2 receptor binding affinity, lipophilicity, % ionization and molecular weight of the radioligand, and the binding capacity of the cerebral tissues. 75Br-BSP gave a striatum-to-cerebellum ratio of 3 in baboon brain 5 h post-injection, which allowed visualization of dopaminergic-receptor-containing areas of the living brain using PET. PMID- 2876898 TI - Renal effects of pinacidil in hypertensive patients on chronic beta-blocker therapy. AB - The acute and chronic effects of pinacidil on blood pressure (BP) and renal function were investigated in 10 patients with moderate arterial hypertension insufficiently controlled by chronic beta-blockade. Acute i.v. administration of pinacidil caused a significant fall in BP of 29.9/18.3 mm Hg and, despite beta blockade, a concomitant rise in heart rate (HR) of 21%. Renal vascular resistance (RVR) showed a marked reduction as a consequence of the fall in BP, and a transient rise in renal plasma flow (RPF). Diuresis and renal clearance of sodium and uric acid showed a parallel fall. The excretion rates of albumin and beta 2 microglobulin were also significantly reduced. Pharmacokinetic studies indicated that glomerular filtration was responsible for elimination of the parent drug, and that proximal tubular secretion was the pathway of excretion of the main metabolite, pinacidil pyridine-N-oxide. During therapy for 4 months there was no further significant reduction in BP, despite increases in the daily dose of pinacidil. The effects on HR were less conspicuous after 4 months; renal haemodynamic parameters and body weight were not significantly changed. The initial level of RVR and the initial acute reduction in this parameter appeared to be major determinants of the long-term BP response. The drug was well tolerated apart from one patient who developed slight fluid retention. However, concomitant administration of a diuretic will probably be necessary during routine use of this therapeutic combination. PMID- 2876899 TI - Comparative single dose and steady-state pharmacokinetics of bevantolol in young and elderly subjects. AB - The pharmacokinetics of bevantolol were examined following single and repeated oral doses to young and elderly volunteers. Following administration of a single 200-mg bevantolol tablet mean maximum plasma bevantolol concentrations in young and elderly subjects were 1690 ng/ml and 1810 ng/ml, respectively. Maximum bevantolol concentrations occurred approximately 1.1 h postdose in both young and elderly subjects. There were no significant differences in mean steady state bevantolol concentrations on Day 14 between young and elderly subjects. However, disproportionate increases in Cmax, and in AUC, but not in tmax values were observed between Days 1 and 14. On Days 1 and 14, most young and elderly subjects exhibited monoexponential decline in bevantolol plasma concentrations after absorption phase. In those subjects Day 14 elimination half-lives in young and elderly were 1.9 and 2.2 h, respectively. In subjects who exhibited biexponential decline in bevantolol, an age effect in elimination became apparent, on Day 14 elimination half-lives were 5.7 and 11.2 h in young and elderly subjects, respectively. Bevantolol Metabolite III concentrations were observed in plasma of some subjects during the first 6 h after dosing. At steady-state AUC (0-ldc) values for the metabolite were less than 2% those of bevantolol. Bevantolol plasma levels accumulate to a small extent with repeated 200 mg daily doses. This is probably due to the contribution of a late and more persistent terminal elimination phase that was discernable in only certain individuals. PMID- 2876900 TI - Pharmacokinetics of TZU-0460, a new H2-receptor antagonist, in patients with impaired renal function. AB - We have studied pharmacokinetics of a new H2-receptor antagonist, TZU-0460, in patients with varying degrees of renal impairment. The apparent volume of distribution at steady-state was 1.70 l/kg, and the plasma protein binding of TZU 0460 or its active metabolite, desacetyl TZU-0460 was less than 10% in normal subjects. These variables were not altered with renal impairment. Sixty percent of TZU-0460 given orally was excreted via the kidney, mainly by tubular secretion. The half-time of elimination was 3.94 h in normal subjects, and was prolonged to 12.13 h in severe renal failure (creatinine clearance below 30 ml/min/1.48 m2). Dosage adjustment of TZU-0460 is necessary in renal failure. PMID- 2876901 TI - Pharmacokinetics of temazepam in geriatric patients. AB - A single dose of temazepam 10 mg, as a solution in soft gelatin capsules, was given to 10 fasting geriatric in-patients (mean age 83 years) in a stable clinical condition. The mean peak plasma concentration was 306 ng/ml, with a median time of 0.75 h to peak concentration. Temazepam was eliminated from plasma in a biexponential manner, with a distribution phase (mean t1/2 alpha = 0.7 h) predominating for 3 h. The drug had a mean elimination half-life of 8.7 h. In a chronic study, in which temazepam 10 mg p.o. was given nightly to 13 patients, the plasma concentrations on Days 3, 5, 8, 12 and 15 were not significantly different from each other, showing rapid attainment of steady state levels and the lack of drug accumulation. PMID- 2876902 TI - Comparison of free MHPG in rat cerebrospinal fluid with free and conjugated MHPG in brain tissue: effects of drugs modifying noradrenergic transmission. AB - The changes of free 3-methoxy-4-hydroxyphenylglycol (MHPG) in cerebrospinal fluid (CSF) were compared with the corresponding alterations of free and conjugated MHPG in rat brain tissue after various pharmacological treatments modifying noradrenergic neurotransmission. In addition, the effects of the drug treatments on the concentration of noradrenaline (NA) in brain were determined. alpha-Methyl p-tyrosine (an inhibitor of tyrosine hydroxylase) induced decreases in free and conjugated MHPG in CSF and brain; the free species appeared to decline more rapidly. Reserpine caused similar biphasic changes in free MHPG in CSF and brain but the rapid and transient initial increase in MHPG-SO4 was very weak. Pargyline (monoamine oxidase inhibitor) induced a sharp decline in the concentration of free MHPG in brain and CSF while MHPG-SO4 in brain definitely decreased more slowly. Relatively similar time courses were seen for all three MHPG parameters after administration of MPV-1248 (alpha 2-antagonist) and clonidine (alpha 2 agonist) i.e., increases and decreases, respectively. The present results support the validity of monitoring drug-induced acute changes in central turnover of NA by repeated measurements of free MHPG levels in rat cisternal CSF. PMID- 2876903 TI - Inhibition of serotonergic dorsal raphe neurons by systemic and iontophoretic administration of buspirone, a non-benzodiazepine anxiolytic drug. AB - Extracellular single-unit recordings were made from serotonergic dorsal raphe neurons in chloral hydrate anesthetized male Sprague-Dawley rats. Buspirone, a clinically effective non-benzodiazepine anxiolytic drug, caused inhibition of firing of these neurons when given by intravenous (ED50 = 0.011 mg/kg, i.v.), intraperitoneal (ED50 = 0.088 mg/kg, i.p.), and intragastric (effective dose = 1.0-20.0 mg/kg, i.g.) injection. Buspirone also inhibited these cells when it was administered to the outside of recorded neurons by microiontophoresis (effective currents = 2-15 nA). Iontophoretically applied buspirone did not potentiate nor block the effects of iontophoretically applied GABA. Systemic administration of two putative buspirone metabolites (1,2-pyrimidinyl piperazine and 5-hydroxy buspirone) in relatively high doses had a weak effect and no effect, respectively, on dorsal raphe neuronal firing. It is concluded that buspirone potently and directly inhibits the firing of serotonergic dorsal raphe neurons in the rat. Since buspirone inhibits the firing of serotonergic dorsal raphe neurons and binds to 5-HT1A receptors, the present study supports the notion that central serotonergic systems may be involved in the therapeutic effects of anxiolytic drugs. PMID- 2876904 TI - Epinephrine-induced memory facilitation: attenuation by adrenoceptor antagonists. AB - The present study examined the relative importance of alpha- and beta adrenoceptors in the memory modulatory effects of epinephrine. Posttraining epinephrine administration enhanced retention performance of a one-trial inhibitory avoidance response. Further pretraining injections of a variety of adrenoceptor antagonists, including selective alpha 1-, alpha 2-, beta 1- and/or beta 2-adrenoceptor antagonists, attenuated the retention enhancing effects of posttraining epinephrine. These results suggest that alpha- and beta adrenoceptors of both subtypes are involved in the memory-modulating effects of epinephrine. PMID- 2876905 TI - Further validation of in vivo and in vitro pharmacological procedures for assessing the alpha 2/alpha 1-selectivity of test compounds: (1). Alpha adrenoceptor antagonists. AB - Twenty one chemically dissimilar alpha-adrenoceptor antagonists were assessed in 7 different tests. The potencies of the compounds to protect rats from norepinephrine lethality were closely correlated with their potencies for inhibition of [3H]WB4101, but not of [3H]clonidine, [3H]idazoxan, [3H]rauwolscine or [3H]yohimbine binding to rat brain homogenates. The reverse was found for the potencies of the compounds to prevent the antidiarrheal effect of clonidine. The in vivo anti-norepinephrine/anti-clonidine potency ratios were highly correlated with the ratios between the in vitro potency to inhibit [3H]WB4101 binding on one hand and [3H]clonidine, [3H]idazoxan, [3H]rauwolscine or [3H]yohimbine binding on the other. The reliability of the above models for measuring alpha 1- and alpha 2 adrenoceptor antagonistic activity and selectivity is discussed. PMID- 2876907 TI - The rhesus monkey: a primate model for hemopoietic stem cell studies. AB - Two heterogeneous cell populations (CP 1-7 and CP 8-10) were separated from rhesus monkey bone marrow using counterflow centrifugation-elutriation (CCE). These two cell populations were distinct with respect to morphological composition, expression of cell surface antigens, hemopoietic progenitor cell activity, and concentration of hemopoietic stem cells (HSC). The hemopoietic progenitor cell activity and HSC were concentrated in CP 8-10. In autologous transplantation studies, CP 8-10 reconstituted the lymphohemopoietic system of lethally irradiated monkeys in a manner similar to that of monkeys transplanted with unfractionated bone marrow cells. CP 1-7 was lymphocyte rich and depleted of progenitor cell activity. Transplantation of CP 1-7 led to eventual lymphohemopoietic reconstitution of irradiated monkeys; however, complete engraftment was delayed by as much as 14 days compared to either the transplantation of CP 8-10 or to unfractionated bone marrow. Thus, a presence of the HSC in the lymphocyte-rich progenitor-cell-depleted population can be detected in the rhesus model. PMID- 2876906 TI - Further validation of in vivo and in vitro pharmacological procedures for assessing the alpha 2/alpha 1-selectivity of test compounds: (2). Alpha adrenoceptor agonists. AB - Eighteen chemically dissimilar alpha-adrenoceptor agonists were assessed in 6 different tests. The antidiarrheal activity of the compounds was highly correlated with the diuretic activity. Both activities were highly correlated with the inhibition of [3H]clonidine or [3H]idazoxan binding; the degree of correlation with inhibition of [3H]WB4101 binding or with antiptotic activity was much less. Antiptotic activity was better correlated, although still poorly, with inhibition of [3H]WB4101 binding than with inhibition of [3H]clonidine or [3H]idazoxan binding. The in vivo antiptotic/diuretic or antiptotic/antidiarrheal potency ratios both reflected the known alpha 2/alpha 1-selectivity of the compounds tested and were significantly correlated with the in vitro potency ratios between inhibition of [3H]WB4101 binding on one hand and of [3H]clonidine or [3H]idazoxan binding on the other. The reliability of the above models for measuring alpha 1- and alpha 2-adrenoceptor agonistic activity and selectivity is discussed. PMID- 2876909 TI - Asthma: non-responsiveness to conventional therapy. AB - Despite regular inhalation of beta-agonists, topical steroids and anticholinergic aerosols and the achievement of therapeutic blood levels of theophylline, some asthmatics have rapidly fluctuating levels of peak flow measurements throughout the day. Often little or no improvement is obtained with larger doses of corticosteroids. Before embarking on more intense drug therapy, attention should be paid to conscientious adherence to the prescribed regimen and avoidance of aspirin and tartrazine, as well as to exposure to allergens such as those associated with household pets. A number of newer therapeutic options are related to the use of air jet or ultrasonic nebulizers, that allow liquid forms of inhalation agents to be taken slowly in the home environment. In this regard, combination therapy with a beta-agonist and the anticholinergic ipratropium has been shown to have bronchodilating properties superior to either agent used alone. Secondly, sodium cromoglycate in its liquid form appears to have bronchodilator properties; taken on a regular basis, four times per day, it appears to have a steroid-sparing effect. Two alternatives are available for increasing the intensity of corticosteroid therapy, other than by prolonged, high dose prednisone. The first is that of high-dose inhaled beclomethasone (up to 2000 micrograms/day) using the 250 micrograms/puff inhaler. The second is that of intravenous therapy with methylprednisolone, recently shown to have lung permeability superior to that of prednisolone. Office patients can be treated with occasional or even regular 'pulse' doses of methylprednisolone, an approach that is now finding acceptance in the management of the inflammatory alveolitides. PMID- 2876908 TI - Hematopoiesis on cellulose ester membranes (CEM). X. Effects of in vitro irradiation of stromal cells prior to application on CEM. AB - Cellulose ester membranes (CEM) were coated with stromal cells from murine bone or bone marrow irradiated in vitro with 1000, 2000, or 4000 rad and then implanted i.p. in CAF1 mice for periods of six and 12 months. CEM coated with stromal cells from bone showed excellent regeneration of bone and hematopoiesis after 1000 rad in vitro irradiation. After 2000 rad, hematopoietic and bone regeneration was reduced by about 50%, and after 4000 rad it was completely absent in CEM coated with stromal cells from bone. CEM coated with stromal cells from bone marrow showed no regeneration of hematopoiesis or bone after 1000, 2000, and 4000 rad in vitro irradiation and residence i.p. for six and 12 months. These results indicate that regeneration of the hematopoietic microenvironment is dependent upon living stromal cells. A difference in radiation sensitivity is demonstrated between stromal cells from bone and from bone marrow. PMID- 2876910 TI - Therapies to control the airway inflammation of asthma. AB - The natural history of the development of airway inflammation in asthma is reviewed together with the known histopathological changes, measurable effects and symptoms. The factors thought to cause the airway inflammation and the associated hyperresponsiveness of the airways are summarized and the stages at which interventions are likely to be effective are indicated. The complications of severe asthma, including early death, are discussed and the aims of therapy are described in relation to these aims. The drugs available to control asthma are briefly reviewed and a practical summary of patient management is given. The potential advantages of this form of treatment, which can be described as 'tight control', are summarized and likely future developments, with emphasis on preventing the disease, are outlined. PMID- 2876911 TI - Why are deaths from asthma increasing? AB - Asthma mortality rates have declined only slowly since 1960, and recently have increased in some countries. Deaths in New Zealand's 5-34 year olds showed a sustained increase from 1977 to 1982. In the western United States, asthma mortality in older subjects increased from 1979 to 1982. In 15-44 year olds in England and Wales, mortality rates for females are now lower than in 1960, but rates for males are not. Current asthma mortality rates for Canadian 5-34 year olds are twice those reported a decade ago. A 2-year national study of all New Zealand patients under the age of 70 whose deaths were certified as due to, or related to, asthma found differences in verified asthma mortality rates among races (Maoris 18.9, Pacific Island Polynesians 9.4, and Europeans 3.4 per 100,000); the higher non-European rates explained 36% of the 'excess' New Zealand mortality compared with England. Errors in certification led to a 13% net overestimate of asthma mortality in both countries, but certification was highly accurate in 5-34 year olds. The increase in asthma mortality in the younger age groups is not an artefact of certification or coding, but is real and substantial. Although factors common to previous studies--poor patient compliance, inadequate assessment and therapy, overreliance on bronchodilators and underuse of corticosteroids, and delays in obtaining help--were frequently recognized, no single cause was found to explain the three-fold greater mortality in New Zealand compared with England.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876912 TI - Airway inflammation and autonomic control. AB - Autonomic nerves control many aspects of airway function, including smooth muscle tone, epithelial cell function, mucus secretion, bronchial flow and permeability, and inflammatory mediator release. There is considerable evidence that there may be abnormalities of autonomic function in asthma, perhaps as a result of airway inflammation. Inflammatory mediators might stimulate bronchial afferent receptors (irritant receptors and C-fibre endings) to produce reflex cholinergic bronchoconstriction. Anticholinergic drugs have not proved to be very effective in controlling clinical asthma, however, suggesting that cholinergic reflex mechanisms may not play a major role. Adrenergic abnormalities have been described in asthma. There is no direct sympathetic neural control of airway smooth muscle, suggesting that circulating catecholamines may regulate airway tone, and counteract the effect of inflammatory mediators in asthma. Surprisingly, the concentration of adrenaline in plasma does not rise in asthmatic subjects with induced bronchoconstriction, or even during an acute asthma attack. The function of beta-adrenoceptors in asthma is uncertain, but there is some evidence that beta-receptor function may be impaired, possibly as a result of inflammatory mediator release. alpha-Adrenoceptor function may be enhanced in asthma; inflammatory mediators may 'turn on' bronchoconstrictor alpha adrenergic responses in airway smooth muscle, and alpha-agonists may have a bronchoconstrictor effect in asthmatic subjects. But specific alpha-blockers have little effect on airway function, and the role of alpha-receptors in asthma is questionable. Non-adrenergic, non-cholinergic nerves are the only neural bronchodilator mechanism in human airways. The neurotransmitter has not yet been identified but vasoactive intestinal peptide (VIP) is a possible candidate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2876913 TI - Restriction endonuclease digest patterns of chromosomal DNA from nitrate-negative Campylobacter jejuni-like organisms. AB - High molecular weight chromosomal DNA was isolated from ten nitrate-negative campylobacters of human origin (gastric biopsies and faecal specimens). The DNA was digested with various restriction endonucleases and the patterns obtained were compared with those of Campylobacter coli, C. fetus subsp. fetus, C. jejuni and C. laridis reference strains. Electrophoresis of Hae III digests of DNA in 0.5% agarose gave excellent patterns which comprised at least 25 well-resolved bands with fragment sizes between about 4 and 40Kb. There were distinct differences between strains from different geographical locations. The six gastric strains from West Germany formed a relatively homogeneous group with respect to their band patterns (type I and II), whereas the U.K. gastric isolate had a slightly different pattern (type III) as did the three Australian faecal isolates (types IV, V and VI). No plasmids were detected in these nitrate negative campylobacters and differences in DNA digest patterns between strains and representatives of allied species were attributed to variations in the distributions of Hae III recognition sequences within the genome. The patterns provided further evidence that the strains were atypical C. jejuni. PMID- 2876914 TI - [Action of antihistaminic agents in patients with various heart pathologies undergoing surgical treatment]. AB - Clinical observations and experimental studies enabled the authors to show that sensitivity of patients with rheumatic heart diseases to antihistaminic drugs is not always constant. It depends on pH value of the medium and blood concentration of calcium ions. It is advisable to include antihistaminic drugs in combination with colloid and crystalloid blood substitutes with regard to pH of the medium into the complex of agents for pre-, intra- and postoperative medication. PMID- 2876915 TI - [Effect of izoturon and its combination with ganglionic blockaders and alpha adrenoblockaders on systemic hemodynamics in traumatic shock]. AB - Isoturone (5 mg/kg) administered in a single dose intravenously to unanesthetized cats in a torpid phase of traumatic shock increases arterial blood pressure (BP) and total peripheral vascular resistance (TPVR). The drug restores BP level mainly due to an increase of TPVR against background of neurovegetative blockade induced by pentamine, phentolamine and combinations of phentolamine with hexonium in the presence of a severe trauma. Vascular sensitivity to isoturone in traumatic shock is preserved and considerably increases during the use of the vasopressor in different types of neurovegetative blockade. PMID- 2876916 TI - Preferential glutamine uptake in rat brain synaptic mitochondria. AB - Glutamine uptake has been studied in purified rat brain mitochondria of synaptic or non-synaptic origin. It was taken up by an active saturable transport mechanism, with an affinity two-times higher in synaptic than in non-synaptic mitochondria (Km = 0.45 and 0.94 mM, respectively). Vmax of uptake was 7-times higher in synaptic mitochondria (Vmax = 9.2 and 1.3 nmol/min per mg protein, respectively). Glutamine transport was found to be inhibited by L-glutamate (IC50 = 0.64 mM) as well as thiol reagents (mersalyl, N-ethylmaleimide). It is suggested that differential uptake of glutamine in mitochondria of synaptic or non-synaptic origin may be a major mechanism in the regulation of the synthesis of the neurotransmitter glutamate. PMID- 2876917 TI - Amino acid substitutions in mitochondrial ATPase subunit 6 of Saccharomyces cerevisiae leading to oligomycin resistance. AB - The amino acid substitutions in subunit 6 of the mitochondrial ATPase complex have been determined for 4 oligomycin resistant mutants of Saccharomyces cerevisiae. The data were obtained for each mutant by nucleotide sequence analysis of the mitochondrial oli2 gene. Amino acid substitutions conferring oligomycin resistance in subunit 6 are located in two conserved regions that are thought to form domains which span the inner mitochondrial membrane. The disposition of these amino acid substitutions is consistent with the view that these two membrane-spanning domains interact structurally and functionally with the DCCD-binding proteolipid subunit 9 in the Fo-sector. PMID- 2876918 TI - Structure of the nucleotide-binding domain in the beta-subunit of Escherichia coli F1-ATPase. AB - We propose a working model for the tertiary structure of the nucleotide-binding domain of the beta-subunit of E. coli F1-ATPase, derived from secondary structure prediction and from comparison of the amino acid sequence with the sequences of other nucleotide-binding proteins of known three-dimensional structure. The model is consistent with previously published results of specific chemical modification studies and of analyses of mutations in the beta-subunit and its implications for subunit interactions and catalytic mechanism in F1-ATPases are discussed. PMID- 2876919 TI - Inhibition of the post-translational processing of microvillar hydrolases is associated with a specific decreased expression of sucrase-isomaltase and an increased turnover of glucose in Caco-2 cells treated with monensin. AB - The biosynthesis and post-translational processing of sucrase-isomaltase and dipeptidylpeptidase IV were studied by L-[35S]methionine labeling, immunoisolation with monoclonal antibodies and SDS-PAGE in post-confluent Caco-2 cells treated with monensin (10 microM, 48 h). In addition to its classical effect on the post-translational processing of both hydrolases, i.e. an inhibition of the conversion of the high-mannose to the complex glycosylated form of the enzymes, monensin was found to have two other effects: a marked decrease of sucrase-isomaltase expression, but not of dipeptidylpeptidase IV; an increased turnover of glucose, as substantiated by increased rates of glucose consumption and lactic acid production and a decreased glycogen content. Whether these two effects are related to the particular differentiation and metabolic status of Caco-2 cells is discussed, as well as a possible role for the drug-induced modifications of glucose turnover on the decreased expression of sucrase isomaltase. PMID- 2876920 TI - Nonclassical synaptic functions of transmitters. AB - Nonclassical synaptic functions are considered in two groups, mainly by reference to the models provided by sympathetic ganglia. Slow postsynaptic potentials (PSPs) are compared with classical fast PSPs. Features include loose delivery of transmitter to receptor, very long synaptic delays and durations of PSPs, slow removal of transmitter or of its effects, integration of repetitive inputs, electrogenesis without large increases in ionic conductances. Neuromodulatory actions affect synaptic efficacy without direct excitatory or inhibitory responses to the transmitter. These include a) control of presynaptic release, and b) contingent postsynaptic actions. In b, a modulatory transmitter alters the efficacy of action by another transmitter. The alteration may persist long after exposure to the modulatory transmitter; in mammalian sympathetic ganglia, exposure to dopamine or to a conditioning train of preganglionic volleys induces a long-term enhancement of the muscarinic slow excitatory PSP. Or the alteration may be restricted mostly to the presence of a modulatory transmitter, with examples cited. Nonclassical synaptic functions may be providing revolutionary possibilities for dealing with slow and broadly distributed cerebral functions, manifested electrophysiologically and behaviorally, that have been difficult to analyze successfully in terms restricted to the fast and discretely localized classical synaptic functions. PMID- 2876921 TI - Central nervous system mechanisms of arterial pressure regulation. AB - This paper provides a review of recent developments in the field of neural and humoral control of the cardiovascular system mediated through the central nervous system. The areas covered include central mechanism of baroreceptor reflex control, sites of origin of tonic vasomotor activity, interactions between forebrain and brain stem, central actions of humoral factors, the role of visceral and somatic afferents, and the potential for central selectivity of vasomotor control. PMID- 2876922 TI - AACN's invitational conference: strategies for the future. PMID- 2876923 TI - Tulobuterol in childhood asthma: single dose ranging and repeated oral dose comparative studies. AB - Fifteen asthmatic patients participated in a dose-ranging study using tulobuterol syrup in single doses of 10 to 60 mcg/kg. A second trial was performed to compare tulobuterol and terbutaline in 64 asthmatic children. The tulobuterol dosages were 30 and 40 mcg/kg twice daily; the terbutaline dosage was 75 mcg/kg three times daily. The dose-ranging study showed that tulobuterol had a rapid and prolonged bronchodilator action, even at the lower doses. Tulobuterol had a more prolonged duration of action than terbutaline in the comparative study. Both drugs had statistically comparable magnitudes of effect. Adverse reactions were minimal. No laboratory abnormalities occurred, and blood pressure and pulse rate were clinically unaffected by either drug. Tulobuterol twice daily had an equal or greater positive clinical effect on pulmonary function in asthmatic children than terbutaline three times a day. PMID- 2876924 TI - Postaggregative differentiation induction by cyclic AMP in Dictyostelium: intracellular transduction pathway and requirement for additional stimuli. AB - Cyclic AMP induces postaggregative differentiation in aggregation competent cells of Dictyostelium by interacting with cell surface cAMP receptors. We investigated the transduction pathway of this response and additional requirements for the induction of postaggregative differentiation. Optimal induction of postaggregative gene expression requires that vegetative cells are first exposed to 2-4 hr of nanomolar cAMP pulses, and subsequently for 4-6 hr to steady-state cAMP concentrations in the micromolar range. Cyclic AMP pulses, which are endogenously produced before and during aggregation, induce full responsiveness to cAMP as a morphogen. The transduction pathway from the cell surface cAMP receptor to postaggregative gene expression may involve Ca2+ ions as intracellular messengers. A cAMP-induced increase in intracellular cAMP or cGMP levels is not involved in the transduction pathway. PMID- 2876925 TI - Oncogene alterations in primary human colon tumors. AB - We have examined alterations in six oncogenes--H-ras, K-ras, N-ras, myc, fos, and N-myc--in nine primary human colon tumors. Tumors were obtained within an hour of resection; as a control for each tumor, adjacent normal colon tissue was also obtained. Deoxyribonucleic acid extracted from each tissue sample was assayed by digesting with appropriate restriction endonucleases and, after gel electrophoresis and transfer to nitrocellulose, hybridizing with radiolabeled oncogene probes. Amplification of the myc locus, relative to adjacent normal colon tissue, was observed in two of these tumors; by dot-blotting, it was estimated that myc was amplified twofold to fivefold in each tumor. No rearrangements of myc, however, were observed in any of these tumors. Examination of the H-ras alleles of these nine tumors revealed that eight possess only "common" alleles of this gene, and that each was identical to its control. Normal colon DNA of the ninth patient, however, was found to possess both a "common" and a "rare" allele, and the "common" allele of H-ras appeared to be deleted in the tumor DNA of this patient. A restriction polymorphism indicative of a mutation in the 12th codon of K-ras was not found in any of these tumors, and we observed no evidence of rearrangement of amplification of the N-ras, K-ras, fos, or N-myc genes. PMID- 2876926 TI - Somatostatin inhibits thyroid function in fowl. AB - Plasma concentrations of thyroxine (T4) and triiodothyronine (T3) were marginally (less than 25%) lowered 10 and 60 min, respectively, following somatostatin (SRIF) administration (at doses of 10-30 micrograms/kg) in immature domestic fowl. When plasma iodothyronine levels were elevated by the administration of anti-SRIF (1.0 ml/kg) 10 min prior to SRIF challenge, the inhibitory effect of SRIF on T4 and T3 concentrations was greatly augmented. The relative reduction in the T3 concentration was greater than the decline in the T4 level, resulting in a decline in the T3:T4 ratio. These data indicate that SRIF inhibits thyroid function in fowl, possibly by direct effects on the thyroid gland and by effects on the peripheral conversion of T4 to T3. PMID- 2876927 TI - Evidence for the presence of adrenocorticotropic and opiate-like hormones in the brains of two sea snakes, Hydrophis cyanocinctus and Lapemis hardwickii. AB - The brain acetone powders of the sea snakes Hydrophis cyanocinctus and Lapemis hardwickii were extracted with a mixture of acetone:water:hydrochloric acid (40:21:1 by volume) and the extracts were then added to a copious volume of acetone, in accordance with the method of C. H. Li (1952, J. Amer. Chem. Soc., 74, 2134) for preparing adrenocorticotropin and beta-endorphin from mammalian pituitaries. The resultant precipitate, designated acid acetone powder, possessed adrenocorticotropic activity as evidenced in its ability to stimulate corticosterone production in isolated rat adrenal decapsular cells and lipolysis in isolated hamster adipocytes, and in its cross-reactivity in an ACTH radioimmunoassay. The presence of opioid molecules was indicated by activity in opiate radioreceptor assay using either 3H-D-Ala2-D-Leu5 enkephalin or [3H]naloxone as ligand and rat brain membranes. The brain acetone powders possessed neither "lactogenic" nor "somatogenic" activity as evidenced by their inability to displace the primary ligand in the rat hepatic prolactin receptor- and growth hormone receptor-binding assays, respectively. PMID- 2876928 TI - The sequence of the chloroplast atpB gene and its flanking regions in Chlamydomonas reinhardtii. AB - The chloroplast (cp)-encoded CF1 ATPase beta-subunit gene (atpB) of Chlamydomonas reinhardtii and its flanking regions have been sequenced. The derived amino acid (aa) sequence is highly homologous to that of the beta-subunit gene in Escherichia coli, bovine heart mitochondria, and higher plant cp. In contrast to all other cp genomes, the CF1 epsilon subunit gene (atpE) does not lie at the 3' end of the atpB gene but maps to a position 92 kb away in the other single-copy region. Northern blots confirm that the beta subunit is not encoded as part of a dicistronic message as it is in higher plants. The region just upstream from the atpB gene in C. reinhardtii contains two small open reading frames (ORFs) and not the gene for the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase as is found in cp genomes of higher plants. No transcripts for either ORF were detected, but the codon usage in these ORFs as well as in the atpB gene follows the unique pattern of codon usage previously seen in other cp genes in C. reinhardtii. PMID- 2876929 TI - [Effect of coal dust on serum urocaninase and aspartate aminotransferase isoenzyme activity]. PMID- 2876930 TI - [Peripheral analgesic actions of opioid peptides and morphine analogues]. AB - Opiates and opioid peptides were administered in the order of 10(-9)-10(-6) mol peripherally, and their action on pain sensitivity was investigated by the modified formalin test which has two characteristic pain responses (the first and the second phase) in the mouse hindpaw. Opioid peptides (20-500 pmol) had dose dependent analgesia against both first and second phases, and their action ranked dynorphin greater than [D-Ala2, Met5]-enkephalinamide greater than [Met5] enkephalin. EKC and morphine (0.4-2.5 nmol) inhibited pain response of the first phase, but produced hyperalgesia in the second phase dose-dependently. Lidocaine hydrochloride had peripheral analgesic action, but was about 500-10000 times weaker than these substances. So, these peripheral analgesic actions have a different mechanism from that of local anesthetic action. N-methyl levallorphan which is thought to be a peripherally selective narcotic antagonist reversed these peripheral analgesic actions at the first and second phases and also prevented the hyperalgesic effects of EKC and morphine at the second phase. Naloxone reversed analgesia at only the first phase. These results suggest that an analgesic mechanism by opioids may exist at the peripheral site as well. Furthermore, it is estimated that a receptor exists which is antagonized by N methyl levallorphan but not by naloxone and that there is a system of hyperalgesia by EKC and morphine in pain modulation. PMID- 2876931 TI - [Effects of cepharanthine on experimental nasal allergy]. AB - The anti-allergic actions of cepharanthine were examined using experimental nasal allergy rats (rhinitis models). In the actively sensitized rhinitis models, leaks of pontamine sky blue (PSB) dye in the perfusate of the nasal cavity were suppressed by cepharanthine treatment. Leaks of PSB dye in the perfusate were also suppressed by ketotifen treatment. beta-Glucuronidase activity in the perfusate was lower in the cepharanthine group and in the ketotifen group. In the passively sensitized rhinitis models, leaks of PSB dye in the perfusate were suppressed by cepharanthine treatment. Leaks of PSB dye in the perfusate in the ketotifen group were also suppressed. However, beta-glucuronidase activity was not different among the three groups. Cepharanthine (0.025-25 mg/kg body weight) and ketotifen (0.1-10 mg/kg body weight) inhibited leaks of PSB into the perfusate in a dose-dependent manner. These results suggest that cepharanthine may be clinically effective for treating patients with nasal allergy, and its anti-allergic mechanism may be the same as that of ketotifen. PMID- 2876932 TI - [Effects of nipradilol, a new beta-blocker, and its metabolite, denitro nipradilol, on heart rate and AV conduction in anesthetized dogs]. AB - Effects of nipradilol, a new beta-blocker, and its metabolite, denitro nipradilol, on heart rate and atrioventricular conduction were investigated in anesthetized dogs and were compared with those of propranolol. The beta-blocking activity of nipradilol was nearly three times as potent as that of denitro nipradilol which was almost the same as the beta-blocking activity of propranolol. Decrease in heart rate (HR) and prolongation of the atrio-His bundle conduction time (AH) were dose-dependently produced by nipradilol (10, 30 and 100 micrograms/kg, i.v.), denitro-nipradilol (30, 100 micrograms/kg, i.v.) and propranolol (30, 100 micrograms/kg, i.v.). The functional refractory period of the atrioventricular node (AVNFRP) was also prolonged by these drugs in a dose dependent manner. The changes in HR, AH and AVNFRP were well correlated to their beta-blocking activities. However, His bundle-ventricle conduction time (HV) was insignificantly affected by these beta-blockers in the doses mentioned above. In the reserpinized and atropinized dogs in which propranolol (100 and 300 micrograms/kg, i.v.) showed very slight, insignificant influence on HR and AH, nipradilol significantly decreased HR and prolonged AH. AVNFRP was also prolonged significantly by nipradilol. These effects of nipradilol were observed even after the administration of propranolol. Denitronipradilol also produced a decrease in HR and prolongations of AH and AVNFRP in reserpinized, atropinized and propranolol-pretreated dogs. These results indicate that nipradilol and its metabolite, denitro-nipradilol, possess a direct depressant action on the sinoatrial node and the atrioventricular node. PMID- 2876933 TI - Functional evaluation of nonsensate free flaps to the sole of the foot. AB - Free flap transfer for soft tissue defects involving the sole of the foot have been important in limb salvage. The functional capacity of 16 patients is documented. From our data, free flaps to weightbearing surfaces of the foot give satisfactory results in patients less than 40 years old and salvage is rewarding. Older patients had less than satisfactory results. When the only alternative is an amputation, free flap salvage may still be indicated. PMID- 2876934 TI - Sensory reinnervation in reconstruction of the foot. AB - Intact sensation constitutes an important protective mechanism for the plantar surface of the foot. For optimal functional results, sensory reinnervation in reconstruction of the heel of the plantar foot would appear to be helpful. Various techniques are presented in which both intact local tissue and distant tissue are used. The design of neurosensory fasciocutaneous flaps and musculocutaneous flaps from the foot, sensory-innervated full thickness skin grafts, and microsurgically transferred skin flaps, muscle flaps, and musculocutaneous flaps are presented. Free tissue transfer techniques can be used in combination with various sensory reinnervation techniques. PMID- 2876935 TI - Orthopaedic aspects of chronic pain. PMID- 2876936 TI - Management of acute lower extremity nerve injuries. AB - While repair of acute nerve injuries in the lower extremity has not been as aggressive as in the upper extremity, there should now be more effective early intervention. Newer microsurgical techniques can be used along with increased understanding of peripheral nerve internal anatomy to obtain more satisfactory repair and reconstruction of the injured nerves. The anatomy and vulnerability of the nerves in the leg are reviewed, and the decision process is analyzed in the context of the functional deficits following such injuries. A priority of goals in lower extremity nerve repair should be established to ensure salvage of the foot. PMID- 2876937 TI - Polymorphism of seminal gamma-glutamyl transpeptidase. AB - Electrophoretic analysis of seminal gamma-glutamyl transpeptidase (GGT) activity of 147 unrelated Japanese males revealed three types of band patterns. An anodal single band, a cathodal single band and heterozygous double bands termed 1, 2 and 2-1, respectively, were commonly identified in the samples. The frequencies of the three types were 1 = 0.22, 2 = 0.33 and 2-1 = 0.44. Seminal stains kept for more than 6 months revealed distinguishable band patterns as well as fresh samples. PMID- 2876938 TI - [Lithotripsy of urinary calculi with laser-induced shock waves]. PMID- 2876939 TI - [The cardioselective beta blocker bisoprolol. Value in the therapy of florid hyperthyroidism]. PMID- 2876940 TI - [Long-term drug therapy of ulcer disease. Findings for deciding, indications, duration and surgical alternatives]. PMID- 2876942 TI - [Better quality of life for the hypertensive patient. 11th International Congress on Hypertension. Heidelberg, 31 August-7 September 1986]. PMID- 2876941 TI - [Reduction of coronary risk factors with selective alpha-blockers. International Doxazosin Symposium. Frankfurt/Main, 7 June 1986]. PMID- 2876943 TI - [Adherence of uropathogenic Escherichia coli and Proteus mirabilis to human uroepithelial cells]. PMID- 2876944 TI - DNA polymorphism related to the idiopathic hemochromatosis gene: evidence in a recombinant family. AB - The metabolic error involved in idiopathic hemochromatosis, as well as the underlying genetic defect remain unknown. It has, however, been recently shown that this genetic lesion occurs at a locus linked to the major histocompatibility complex, probably close to the HLA-A locus, and that the disease is recessively transmitted. Therefore, in a family where one subject has idiopathic hemochromatosis his HLA-identical siblings should also be affected. We present here the restriction polymorphism with two MHC class I probes and one DR beta probe in an exceptional family with three HLA-identical siblings: one (the proband) has a major form of idiopathic hemochromatosis, while the other two are free of any clinical or biochemical signs of the disease. The restriction patterns observed after DNA digestion by enzymes EcoRI, EcoRV, BglII, BamHI, PvuII, TaqI, HincII, and HindIII led to the conclusion that one of the proband's chromosome 6 had undergone two alterations: one, a deletion in the DR region, was revealed by missing fragments all correlated with DR5; the other was an unbalanced cross-over or a genetic conversion in the MHC class I region. This latter alteration was revealed by modifications in the patterns of high molecular weight HindIII bands which hybridize with probe pHLA2 and also by the absence of a HindIII fragment of 7.4 kb hybridized by another class I probe. This latter alteration most likely involved the hemochromatosis gene and could be the first step toward a molecular approach to this gene. PMID- 2876945 TI - A 45,X male with a Yp/18 translocation. AB - A patient described as a 45,X male (Forabosco et al. 1977) was examined for the presence of Y-specific DNA by using various probes detecting restriction fragments from different regions of the Y chromosome. Positive hybridization signals were obtained for Yp fragments only. In situ hybridization with two different probes, pDP31 and the pseudoautosomal probe 113F, led to a clear assignment of the Yp sequences to the short arm of one chromosome 18. Cytogenetically, the presence of all of Yp including the Y centromere on 18p could be demonstrated replacing a segment of similar size of 18p. Thus, the Y/18 translocation chromosome is dicentric structurally, but it was shown to be monocentric functionally with the no. 18 centromere active. Gene dosage studies with the probe B74 defining a sequence at 18p11.3 demonstrated a single dose of this sequence in the patient. In agreement with these observations, the patient shows clinical signs of the 18p-syndrome. It is concluded that in XO males in general, the X is of maternal origin while the maleness is due to a de novo Y/autosome translocation derived from the father. Depending on the nature of the autosomal deficiency caused by the Y/autosome translocation, the patient may have congenital malformations. PMID- 2876946 TI - ApoA-I related DNA polymorphism in humans with coronary heart disease. AB - A genetic analysis of atherosclerotic patients as well as healthy subjects using an apoA-I gene specific probe confirmed that an EcoRI restriction fragment length polymorphism is related to the development of atherosclerosis. Three subjects with severe coronary heart disease were found to be homozygous for a 6.5 kb fragment hybridizing to the apoA-I probe. In the atherosclerotic patient group 44% were heterozygous for this fragment, compared to 9.5% in the control group. The distribution of genotypes in the atherosclerotic and control groups was significantly different. Among the heterozygous subjects, specific differences were found after digestion of their DNA with Bam HI restriction endonuclease. PMID- 2876947 TI - Genetic linkage between X-linked retinitis pigmentosa and DNA probe DXS7 (L1.28): further linkage data, heterogeneity testing, and risk estimation. AB - Further linkage data relating X-linked retinitis pigmentosa and DNA probe DXS7 (L1.28) is presented in this paper. The current mean estimate of the recombination fraction (theta) including this and all published data, is 0.09, with confidence limits 0.04 to 0.17 (maximum Lod score of 14.01 at a theta of 0.08). There is no evidence for heterogeneity of recombination fraction between the 13 families for which data are available. However, it is argued that heterogeneity should be assumed to exist for the purposes of risk estimation. Mean estimates and variances of risk are calculated for hypothetical families each with different linkage data. In families in which no recombination has been observed, the mean and variance of risk are sufficiently small for the clinical use of this probe to be acceptable to many. PMID- 2876948 TI - Integrity of the thyroglobulin locus in tricho-rhino-phalangeal syndrome II. AB - The thyroglobulin gene has been mapped to chromosome band 8q24 by several investigators. This is the band implicated in the causation of Langer-Giedion syndrome (tricho-rhino-phalangeal syndrome II). We have examined a restriction fragment length polymorphism at the thyroglobulin locus in a patient with Langer Giedion syndrome and 8q deletion in order to: (1) localize the Langer-Giedion deletion more precisely, (2) define the relative map positions of the thyroglobulin gene and the Langer-Giedion locus. The results indicate that the locus of the thyroglobulin gene is intact in the patient with an interstitial deletion of proximal band 8q24.1 which confirms its more distal localization reported earlier by Berge-Lefranc et al. (1985). It also assigns the critical region for the causation of Langer-Giedion syndrome to the proximal part of band 8q24, viz. 8q24.11----q24.13. PMID- 2876950 TI - Fatigue and reading of text on videotex. PMID- 2876951 TI - Drug-induced piloerection in man: an alpha 1-adrenoceptor agonist effect? AB - The physiology of piloerection is described and clinical experience is discussed. The objective and subjective evidence for drug-induced piloerection by a number of drugs is given and, where it is known, their pharmacological mechanism is described. The results are considered in relation to the hypothesis that drug induced piloerection is only produced by drugs with alpha 1-adrenoceptor agonist activity. For those drugs without the latter activity where piloerection is supported only by subjective evidence it is suggested that objective evidence should be sought. The fact that there is no objective evidence that the classical alpha 1-adrenoceptor agonist, phenylephrine, produces piloerection is found surprising and it is suggested that such evidence should be sought. If it is found that phenylephrine does not produce piloerection, then the possibility of the existence of a further alpha-agonist subgroup needs to be considered. PMID- 2876949 TI - De novo DNA microdeletion in a girl with Turner syndrome and Duchenne muscular dystrophy. AB - The single X chromosome of a girl with Turner syndrome (45,X) and typical Duchenne muscular dystrophy was investigated at the chromosomal and DNA levels. No visible abnormality of the residual X chromosome was found upon high resolution R-banding. The DNA was analysed by Southern blotting and hybridization with seven cloned probes mapping in the Xp21 region where the Duchenne locus is thought to be located. A molecular deletion was detected with probes pERT 87.1, pERT 87.8, and pERT 87.15. The other probes (754, C7, 99.6, and RC8) gave a normal signal. The DNA alleles seen in the two parents indicated that the deletion found in the propositus had occurred de novo on a maternal X chromosome. PMID- 2876952 TI - Influence of a minor recurrent idiotype on the regulation of immune response: route dependence. AB - Sp6, a BALB/c hybridoma, produces anti-TNP IgM antibodies (AB), which carry a minor recurrent idiotype (ID). Despite the fact that only about 20% of BALB/c anti-TNP AB carry the Sp6 ID, injection of Sp6-coated spleen cells (Sp6-SC) significantly influenced the anti-TNP B cell response. Repeated intratrail (i.t.) or intravenous (i.v.) injections of Sp6-SC resulted only in a minor increase of the anti-TNP background response. When mice consecutively were challenged with TNP-horse red blood cells (HRBC), i.t. injections of Sp6-SC resulted in a 2-3 fold increase in the number of anti-TNP plaque-forming cells (PFC), while i.v. injection of Sp6-SC displayed no effect on a primary anti-TNP response. But, after i.v. as well as i.t. application of Sp6-SC, it was not possible to obtain hapten-specific suppression by i.v. injection of TNP-haptenized lymphocytes. In vitro characterization of the underlying mechanism revealed that the helper effect, which only was observed after i.t. injection, was due to a Lyt-1+ population, not adhering to Sp6-coated plates, while counterregulation of hapten specific suppression was found in a Lyt-2+ population, adhering to Sp6-coated plates. Hence, depending on the route of priming, injection of AB with a recurrent ID can augment the response towards the nominal antigen either directly via activation of helper cells or indirectly via activation of counterregulatory cells. PMID- 2876954 TI - Morphine-like effects of alpha 2 adrenergic agonists on cortical EEG in rats. PMID- 2876955 TI - In vitro antimicrobial effects of furazolidone & metronidazole. PMID- 2876953 TI - Adenosine induced production of a soluble factor affecting lymphocyte activation. AB - We show that a brief exposure of human peripheral blood mononuclear cells (PBMC) to adenosine or to theophylline results in a mitomycin C resistant regulatory activity. Adenosine induced suppression is also detectable in a lymphocyte subpopulation (T4+ enriched, originally described as helper inducer) resistant to the theophylline induced loss of capacity to form spontaneous rosettes with sheep erythrocytes (TTR). This activity is apparently dependent on the production of a soluble factor(s) since supernatants from adenosine treated TTR (SnA) exert a significant inhibition on the proliferative response of resting lymphocytes. On the contrary SnA increases the concanavalin A (ConA) preactivated lymphocytes proliferation. Similar results are detectable on the proliferative response in the mixed lymphocyte reaction (MLR). Perhaps these effects are related to different Interleukin 2 (Il 2) receptor expression on the cell surface of the resting and preactivated populations. A slow moving band corresponding to a protein of Mr of 64,500 and isoelectric point 7.6 is present in SnA. Only a slight Il 2 activity is detectable either in SnA and in control supernatant (SnC). These findings suggest that SnA may be a dynamic regulator of the early stages of lymphocyte activation. PMID- 2876956 TI - Postsynaptic alpha 1- and alpha 2-adrenergic receptors in adrenergic control of capacitance vessel tone in vivo. AB - The involvement of postsynaptic alpha 2-adrenergic receptors in the adrenergic constriction of the capacitance vessels was studied in anesthetized, spontaneously breathing dogs under ganglionic blockade (hexamethonium, 10 mg/kg + 10 mg/kg/hr; methylatropine, 0.5 mg/kg). Effective vascular compliance was measured as an indicator of venous tone (blood volume was varied by +/- 4 ml/kg in an 11-minute cycle of infusion, withdrawal, withdrawal, and reinfusion) and was calculated from the correlation between the observed changes in central venous pressure and the changes in blood volume. Sympathetic activity and central venous pressure were lower and effective vascular compliance was higher than values in untreated conscious dogs. The alpha 2-agonist UK 14,304 (5-bromo-6 [imidazolin-2-ylamino]-quinoxaline; 0.04 and 0.12 micrograms/kg/min; n = 6) dose dependently lowered compliance and increased central venous pressure to levels found in conscious dogs, as did the alpha 1-agonist methoxamine (10 and 30 micrograms/kg; n = 6). Rauwolscine (alpha 2-antagonist), 0.3 mg/kg, significantly attenuated the effects of UK 14,304, but not those of methoxamine, while prazosin (alpha 1-antagonist), 0.12 mg/kg, attenuated the effects of methoxamine, but not those of UK 14,304 (n = 6 each). Under beta-blockade (nadolol, 2 mg/kg; n = 12) venous tone was increased to about physiological levels by norepinephrine, 0.15 micrograms/kg/min i.v., or by neuronal norepinephrine release induced by tyramine, 10 micrograms/kg/min i.v. These increases were significantly attenuated by prazosin as well as by rauwolscine and were abolished by a combination of both. These results indicate that postsynaptic alpha 2-adrenergic receptors (in addition to alpha 1-adrenergic receptors) are functional in the venous system in vivo and contribute substantially to adrenergic sympathetic and humoral regulation of venous tone. PMID- 2876957 TI - Surface proteins of Bordetella pertussis: comparison of virulent and avirulent strains and effects of phenotypic modulation. AB - The surface proteins of several Bordetella strains and their modulated derivatives were examined by surface radioiodination, cell fractionation, and Western blotting. A surface protein with a high Mr, missing in a mutant lacking the filamentous hemagglutinin, was identified in virulent Bordetella pertussis and Bordetella parapertussis cells and was absent in avirulent B. pertussis strains. The electrophoretic profiles of lipopolysaccharide and the 40,000-Mr anion-selective porin were not determinants which correlated with phase variation or phenotypic modulation. At least three envelope proteins (91,000, 32,000, and 30,000 molecular weight) were found only in virulent B. pertussis strains and were absent or diminished in the avirulent phase and most phenotypically modulated strains. Two transposon-induced mutants unable to produce hemolysin, dermonecrotic toxin, pertussis toxin, and filamentous hemagglutinin also lacked these three envelope proteins, confirming that virulence-associated envelope proteins were genetically regulated with other virulence-associated traits. PMID- 2876958 TI - Binding of Escherichia coli S fimbriae to human kidney epithelium. AB - Purified S fimbriae and an Escherichia coli strain carrying the recombinant plasmid pANN801-4 that encodes S fimbriae were tested for adhesion to frozen sections of human kidney. The fimbriae and the bacteria bound to the same tissue domains, and in both cases the binding was specifically inhibited by the receptor analog of S fimbria, sialyl(alpha 2-3)lactose. S fimbriae bound specifically to the epithelial elements in the kidneys; to the epithelial cells of proximal and distal tubules as well as of the collecting ducts and to the visceral and parietal glomerular epithelium. In addition, they bound to the vascular endothelium of glomeruli and of the renal interstitium. No binding to connective tissue elements was observed. The results suggest that the biological function of S fimbriae is to mediate the adhesion of E. coli to human epithelial and vascular endothelial cells. PMID- 2876959 TI - Localization of binding sites for purified Escherichia coli P fimbriae in the human kidney. AB - Binding sites in the human kidney for purified P fimbriae of pyelonephritogenic Escherichia coli were determined. The purified KS71A (F7(1)) fimbriae bound only to epithelial elements of the kidney, i.e., to the apical aspect of proximal and distal tubular cells, as well as to the apical and cytoplasmic sites of collecting ducts. In addition, binding was seen at the vascular endothelium throughout the kidney and at the parietal epithelium of the glomeruli. The binding was specifically inhibited by the receptor analog of E. coli P fimbriae, globotriose. The binding sites identified suggested a possible pathogenetic mechanism for the invasion of P-fimbriated bacteria into the renal parenchyma, as well as for their subsequent spread into the circulatory system. PMID- 2876960 TI - Inability of pyrogenic, purified Bordetella pertussis lipid A to induce interleukin-1 release by human monocytes. AB - Free lipid A of Bordetella pertussis, Neisseria meningitidis, and Escherichia coli lipopolysaccharide (LPS) was prepared by hydrolysis in acetate buffer (pH 4.5); in addition, lipid A from B. pertussis and E. coli was prepared by hydrolysis in mineral acid (HCl). The precipitates obtained were purified by extraction methods in toluene-methanol and are referred to as crude lipid A. Purified lipid A from N. meningitidis and B. pertussis was obtained by extraction in a mixture of chloroform-methanol-water-triethylamine. The different preparations were tested for their pyrogenicity (endogenous pyrogen; EP) and their capacity to trigger the release of interleukin-1 (IL-1; previously known as lymphocyte-activating factor; LAF) by human monocytes. Crude lipid A from E. coli and N. meningitidis were both IL-1 inducers. Crude B. pertussis lipid A (acetate buffer; pH 4.5), which contains a beta-1-6-linked D-glucosamine disaccharide, two phosphoryl groups, and five fatty acids, was pyrogenic and an IL-1 inducer (EP+/LAF+); but crude B. pertussis lipid A (0.25 N HCl), which lacked the glycosidic phosphoryl group, was 1,000-fold less pyrogenic than the diphosphorylated lipid A, yet it retained its IL-1-inducing capacity (EP-/LAF+). Purified N. meningitidis lipid A was not an inducer of IL-1 release and purified B. pertussis lipid A exhibited identical pyrogenicity as the parent LPS but was devoid of any IL-1-release inducing capacity (EP+/LAF-). These results demonstrate that for some endotoxins, purified lipid A is unable to induce IL-1 release by human monocytes; however, it is pyrogenic, supporting the hypothesis that IL-1 and EP are induced by different determinants on the LPS molecule. PMID- 2876961 TI - Type 2 fimbrial lectin-mediated phagocytosis of oral Actinomyces spp. by polymorphonuclear leukocytes. AB - Phagocytosis of Actinomyces viscosus T14V and A. naeslundii WVU45 by human polymorphonuclear leukocytes in the absence of antibody or complement was mediated by the lectin associated with the type 2 fimbriae of these bacteria. This effect was markedly enhanced by exogenous sialidase, an enzyme also secreted by these actinomyces. Since sialidase treatment of the bacteria did not result in increased phagocytosis, this enzyme presumably acts by unmasking receptors for the fimbrial lectin on phagocytic cells. The viability of A. viscosus T14V, which possesses type 1 and type 2 fimbriae (1+ 2+), and A. naeslundii WVU45, which possesses only type 2 fimbriae (2+), was decreased by at least 98% following incubation with polymorphonuclear leukocytes in the presence of sialidase. Entirely analogous findings were obtained with a 1- 2+ mutant of A. viscosus T14V. In contrast, the phagocytosis of 1+ 2- and 1- 2- mutants of A. viscosus T14V and a 2- mutant of A. naeslundii WVU45 was minimal or absent. Lactose and beta-methylgalactoside inhibited the destruction of the bacteria, whereas cellobiose and alpha-methylgalactoside were ineffective. Thus, the type 2 fimbriae of the oral actinomyces recognize galactose-containing receptors on polymorphonuclear leukocytes which have been exposed by the removal of sialic acid, an interaction that is followed by internalization and subsequent killing of the bacteria. PMID- 2876963 TI - Modulation of Actinomyces viscosus colonization of mouse teeth in vivo by immunization with fimbrial adhesins. AB - Experiments were performed to determine whether immunization of mice with fimbrial adhesins isolated from Actinomyces viscosus T14V could modulate infection of tooth surfaces in animals challenged with the homologous strain. Saliva and sera from animals immunized in the submandibular gland region contained elevated levels of fimbria-specific immunoglobulin A (IgA) and IgG, whereas saliva and sera from sham-immunized animals did not. There was a statistically significant inverse correlation between the presence of fimbria specific antibodies in saliva and serum and the levels of bacterial colonization on molar tooth surfaces. These results suggest that fimbrial adhesins may effectively modulate infection of tooth surfaces by periodontopathic bacteria. PMID- 2876962 TI - Fimbria-specific antibodies in serum and saliva of mice immunized with Actinomyces viscosus T14V fimbriae. AB - Fimbria-specific antibody responses were compared in mice immunized with purified fimbrial adhesins in the region of the submandibular gland (i.e., local site) or at a remote site in the back. One hundred micrograms of fimbriae isolated from Actinomyces viscosus T14V was used as the vaccine. Four subcutaneous injections of the vaccine in the local site induced greater amounts of fimbria-specific immunoglobulin G (IgG) in serum and saliva than three injections. However, there was no difference in the response of fimbria-specific IgA in serum and saliva. Fimbria-specific IgG in serum and saliva were first detected 21 days after the primary immunization at both the local or remote sites. Fimbria-specific IgA in serum was first detected 28 days after the primary immunization at both the local or remote sites. However, fimbria-specific IgA in saliva occurred only in mice immunized with the fimbrial vaccine at the local site and was first detected 14 days after the primary immunization. Both serum and saliva from mice immunized 4 times with the fimbrial vaccine in the local site inhibited in vitro adsorption of strain T14V cells to hydroxyapatite beads pretreated with normal mouse saliva, whereas adsorption of strain T14V cells suspended in serum and saliva from sham immunized animals was not inhibited. Collectively, these data suggest that mice immunized locally in the submandibular gland region with a vaccine composed of purified fimbrial adhesins provide a potential model for evaluating the efficacy of fimbria-specific antibodies in saliva to inhibit strain T14V colonization of tooth surfaces. PMID- 2876965 TI - Anesthetic considerations for craniotomy in awake patients. PMID- 2876966 TI - Enzyme immunoassay with cell suspensions: studies on reactions between serum antibodies and cell-surface antigens. AB - The following reactions of serum antibodies with cell surface antigens were studied by means of an enzyme immunoassay with cell suspensions: Rh antiserum with human red blood cells; H-2 antisera with murine red blood cells; H-2 antisera with murine thymocytes and hepatocytes; Thy-1 antiserum with murine thymocytes; polyvalent and monovalent HLA alloantisera with human leukocytes and human mononuclear cells, and antisera of murine origin with human and marmoset lymphoid cell lines. In all instances, with the exception of monovalent HLA antisera, the assay proved to be a sensitive and highly specific procedure. PMID- 2876964 TI - Change in degree of type 1 piliation of Escherichia coli during experimental peritonitis in the mouse. AB - To determine whether expression of type 1 pili varies during the course of Escherichia coli infection in vivo, mice were injected intraperitoneally with 5 X 10(7) CFU of piliated or nonpiliated phase variants per ml, and the degree of piliation was measured in peritoneal exudate by an enzyme-linked immunosorbent assay inhibition method. In the animals challenged with the piliated bacteria, the numbers of organisms increased a log over 9 h and the amount of pilus antigen decreased from 3 to 0.075 micrograms/10 bacteria. After a 4-h delay, nonpiliated bacteria also increased by one log over 9 h; however, the amount of piliation remained virtually undetectable. Piliated E. coli were more virulent than nonpiliated variants in this model (50% lethal dose of 7.5 X 10(6) versus 3 X 10(7), respectively). The difference was significantly reduced by prior passive immunization with rabbit serum containing high titers of antipili antibody. Piliated bacteria adhered in significantly greater numbers to isolated mouse peritoneal membranes than did nonpiliated variants (15,400 +/- 2,700 versus 1,300 +/- 700 bacteria/mm2, respectively; P = 0.05). Adherence was inhibited by the presence of 0.1 M alpha methyl mannose (1,500 +/- 1,800 bacteria/mm2, P = 0.01). These results confirm the results of previous qualitative studies showing that phase variation of type 1 pili occurs in vivo and suggest that these pili may confer an initial advantage for growth of E. coli in the peritoneal cavity, presumably by fostering colonization of the peritoneal serosal surface. PMID- 2876967 TI - [Experimental basis of the analgesic action of tiapride in dentistry]. PMID- 2876968 TI - A technique for simultaneous microangiographic and cytochemical investigation of resin-embedded tissues. AB - A method for simultaneous acquisition of information on cytochemical and microangiographic characteristics of tissue after perfusion with contrast medium was developed. The technique is based on the use of hydrosoluble resin as embedding material and is illustrated by the demonstration of gamma glutamyltranspeptidase activity and of the microcirculation in rat liver during chemically induced hepatocarcinogenesis and experimental metastasis. The method is applicable to investigations aimed at correlating microangiographic and cytochemical characteristics of normal or altered tissues. PMID- 2876969 TI - Doppler test after microvascular anastomoses and evaluation of somatostatin administration in segmental canine pancreas autotransplantation. A preliminary study. AB - Segmental pancreatic transplantation still involves a certain number of possible technical complications. The experimental studies in dogs reported here evaluate the effectiveness of vascular microanastomoses using doppler velocimetry in two groups of dogs which underwent segmental pancreatic autotransplantation. One group was protected by intraoperative somatostatin infusion, while the other was kept as control. The obtained results indicate that the doppler-test revealed early vascular complications (2/20 animals) and that somatostatin administration may play a major role in the prophylaxis of pancreatitis. PMID- 2876970 TI - The pharmacologic management of coronary artery disease in 1986. PMID- 2876971 TI - Fluorine-18 labeled receptor based radiopharmaceuticals. PMID- 2876972 TI - New forms of hereditary tyrosinemia type II in mink: hepatic tyrosine aminotransferase defect. PMID- 2876973 TI - Neurotransmitter deficits in Alzheimer's disease and in other dementing disorders. AB - The evidence for deficiencies in neurotransmitters in Alzheimer's disease is reviewed. Major losses occur in the subcortical afferent projection systems based on acetylcholine, noradrenaline and serotonin. Within the cortex, somatostatin containing neurones and the large pyramidal cells, presumed to use glutamate/aspartate as transmitters, are the most severely damaged cells. The anatomical distribution of cell loss is explainable if the primary site of damage lies within the cortex; nerve cells are damaged by virtue of their presence within or their connections to this region. The senile plaque may represent the site of this damage and neurofibrillary tangle formation and accumulation may lead to cell death. In patients with Down's syndrome who live past 40 years, changes in transmitters apparently identical to those in Alzheimer's disease occur. The dementia of Parkinson's disease appears related to damage to cholinergic, noradrenergic and dopaminergic systems and may reflect a failure of these subcortical regions to sufficiently "activate" an otherwise undamaged cortex. PMID- 2876974 TI - Neurotransmitters in the human and nonhuman primate basal ganglia. AB - In recent years, a number of new molecules, particularly peptides, have been identified as putative neurotransmitters. The basal ganglia, is especially rich in a number of classical transmitter molecules, amino acids and neuropeptides considered to function in neurotransmission. These include: the well-described terminal fields in the striatum which originate from the brain stem and contain the monoamines, dopamine and serotonin; amino acid containing axons projecting from the cortex and thalamus; striatal cholinergic and peptide-positive interneurons; and amino acid and peptide containing projection neurons to the globus pallidus and substantia nigra. Two amino acids, glutamate and aspartate, are considered to provide excitatory input to the striatum while gamma aminobutyric acid is thought to mediate inhibitory output. Neuropeptides which are richly concentrated in the basal ganglia include, enkephalin, dynorphin, substance P, somatostatin, neuropeptide Y and cholincystokinease. Changes in many of these peptide levels have recently been associated with a number of basal ganglia disorders. PMID- 2876975 TI - Transmitter systems in the primate dentate gyrus. AB - While the dentate gyrus is clearly the simplest of the cortical fields that constitute the hippocampal formation, it nonetheless occupies a pivotal position in the flow of information through this region. Though it has been the subject of anatomical study for over a century and its major connections have been known for almost as long, the use of newly developed histochemical and immunohistochemical techniques have demonstrated many new facets of its intrinsic connectivity and afferent innervation. These techniques have established that it is innervated by cholinergic, noradrenergic, serotonergic and dopaminergic fibers. More recent studies have shown that fibers and cell bodies of the dentate gyrus are immunoreactive for variety of neuroactive substances including the excitatory amino acids glutamate and aspartate, the inhibitory transmitter GABA, as well as peptides of many types including the opioid peptides, enkephalin and dynorphin, several forms of somatostatin, neuropeptide Y, cholycystokinin, vasoactive intestinal peptide and substance P. In this review, we will briefly summarize the distribution of each of these putative transmitter systems within the dentate gyrus. The perspective emerges that the plethora of newly identified and chemically specific fiber systems enriches the classical understanding of the organization of this relatively simple cortical structure. Since there is thus far no evidence for the exclusion from the dentate gyrus of any class of transmitter bearing fiber or neuron found in the neocortex, it can be viewed as a relatively simple model system for studying the interactions of specific transmitter systems in a laminated, cortical structure. PMID- 2876976 TI - Anaerobic bacterial infections and response to treatment in dogs and cats: 36 cases (1983-1985). AB - Anaerobic bacteria have been increasingly implicated as important pathogens in animals. To determine the prevalence of anaerobic bacterial infection, the results of anaerobic bacteriologic culture of 599 specimens obtained from dogs and cats hospitalized at the Colorado State University Veterinary Teaching Hospital were reviewed. Obligate anaerobic bacteria were isolated from 35% of properly submitted specimens; Bacteroides spp and Fusobacterium spp were the organisms most commonly isolated. Infections most often containing anaerobes were abscesses, pleuropulmonary infections, and abdominal infections. A complication rate of 28% was observed with anaerobic bacterial infections; failure to initially treat with an effective antibiotic increased the rate of recurrence of infection. PMID- 2876977 TI - Absolute neutrophilia in adult T cell leukemia. AB - The numbers of neutrophils and platelets and the serum calcium (Ca) levels were examined in 12 patients with lymphoma-type adult T cell leukemia (ATL) and 35 patients with leukemic-type ATL. The same parameters were also studied in 17 patients with non-Hodgkin's lymphoma and 22 patients with acute lymphocytic leukemia as controls. The numbers of neutrophils and the serum Ca levels were significantly higher in leukemic-type ATL (P less than 0.01) and lymphoma-type ATL (P less than 0.05) than in the controls. However, no statistically significant correlation between the numbers of neutrophils and the levels of serum Ca in ATL was observed. Thus, these two abnormal clinical features might be caused by different humoral factors. PMID- 2876978 TI - Acetyl-CoA carboxylase of sheep adipose tissue: problems of the assay and adaptation during fetal development. AB - The rate of fatty acid synthesis of perirenal adipose tissue of fetal lambs decreased by 90% during the last month of gestation. There was also a 90% decrease in the activity of fatty acid synthetase during this period, but the activity of this enzyme exceeded lipogenic flux by a factor of 10. The activity of acetyl CoA carboxylase in the active state (initial activity) was very similar to the lipogenic flux in adipose tissue from lambs at 120 d of gestation; although activity decreased towards term, the decline was insufficient to account for the fall in rate of fatty acid synthesis. The study also shows that assay of acetyl CoA carboxylase in the active state of ovine adipose tissue and of caprine mammary gland requires the presence of citrate, thus differing from that for rat adipose tissue. Evidence that pyruvate carboxylase can interfere in the assay of acetyl CoA carboxylase also is presented. PMID- 2876979 TI - Evaluation of capillary gas chromatography for multicomponent drug analysis. AB - Capillary gas chromatography is evaluated for multicomponent drug analysis. A 0.32 mm id X 30 m fused silica column and a 0.75 mm id X 30 m borosilicate glass column (both with OV-1 bonded phase) are investigated. Retention times (relative to caffeine) are presented for 39 drug components representing a variety of chemical classes and pharmacological activities. Reproducibility data are presented for both isothermal and programmed temperature runs on selected drug mixtures. Recovery data are provided for 2 multicomponent drug mixtures prepared to approximate over-the-counter antihistaminic and antitussive preparations. PMID- 2876980 TI - Colorimetric determination of C-2 unsubstituted phenothiazines, using morpholine and N-bromosuccinimide. AB - A colorimetric method for quantitative determination of 6 C-2 unsubstituted phenothiazine derivatives is described. The method is based on reaction of phenothiazine derivative with morpholine and N-bromosuccinimide reagents in aqueous methanol at 60 degrees C to produce a blue color. Beer's law is obeyed in a wide range of concentrations for all 6 compounds at 660 nm. Optimum analytical conditions were determined and the produced color is stable for at least 24 h. Analytical data for determination of the pure compounds are presented together with the application of the proposed method to analysis of some pharmaceutical preparations. The results compare favorably with those of official methods. Furthermore, the method is specific for intact drug in the presence of oxidative decomposition products. The reaction product has been isolated and identified and a possible reaction mechanism is suggested. PMID- 2876981 TI - Polyarteritis nodosa--unusual presentation (an autopsy report). PMID- 2876982 TI - The stimulant challenge test in depression. AB - The psychostimulants remain controversial agents for the diagnosis and treatment of depression. One promising area of investigation involves the use of a brief trial of a stimulant to predict patient response to subsequent treatment with a tricyclic antidepressant. Five of 10 studies have demonstrated the predictive value of the stimulant challenge test in depression; however, these studies have varied significantly in method. Studies in which oral doses of stimulant were given over an extended time have demonstrated greater predictive value than studies using a single intravenous challenge dose. Additional factors which differ between studies and may affect the predictive value of the stimulant challenge test are identified. The literature on the neuroendocrine responses to stimulant administration, direct stimulant effects on mood and activity, and stimulant neurotransmitter effects is summarized to further understanding of stimulant action in relation to affective disorders. PMID- 2876983 TI - Protein kinase C enhances growth hormone releasing factor (1-40)-stimulated cyclic AMP levels in anterior pituitary. Actions of somatostatin and pertussis toxin. AB - The brain peptide human growth hormone releasing factor (1-40) (GRF), which stimulates adenylate cyclase activity in the anterior pituitary, is the predominant hormone signal for pituitary growth hormone (GH) release. Activators of protein kinase C such as teleocidin and 4 beta-phorbol 12-myristate 13-acetate (PMA) double the cyclic AMP accumulation induced by GRF, with no apparent effect on GRF potency; an inactive 4-alpha-PMA has no such action in cultured anterior pituitary cells. This PMA potentiation can be measured as early as 60 s, is maximal by 15 min, and wanes such that by 3-4 h there is no such amplifying effect of PMA. PMA, phorbol 12,13-dibutyrate, and teleocidin ED50 values for potentiating GRF activity are similar to those obtained for direct protein kinase C activation. The major inhibitory peptide somatostatin reduced both GRF- and GRF + PMA-stimulated cyclic AMP accumulation. Pertussis toxin totally blocked this somatostatin action without affecting the degree of maximal GRF potentiation achieved with PMA. Thus, the pertussis toxin target(s) are required for somatostatin inhibition of the cyclic AMP generating system, but may not be involved in the PMA potentiation of GRF-stimulated cyclic AMP accumulation. PMID- 2876984 TI - Inactivation of the bovine heart mitochondrial F1-ATPase by 5'-p fluorosulfonylbenzoyl[3H]inosine is accompanied by modification of tyrosine 345 in a single beta subunit. AB - The inactivation of the bovine heart mitochondrial F1-ATPase by 5'-p fluorosulfonylbenzoylinosine (FSBI) proceeds with pseudo-first order kinetics. The rate of inactivation increased from pH 7 to 9 revealing a pKa of about 8.2. When a tryptic digest of the enzyme which had been inactivated with 5'-p fluorosulfonylbenzoyl[3H]inosine ([3H]FSBI) was submitted to reversed phase high pressure liquid chromatography, a single major peak of radioactivity, T1, was resolved. Amino acid sequence analysis of purified peptide fragments derived from T1 showed that the modification of beta-Tyr-345 is responsible for inactivation of the enzyme. Complete inactivation of the enzyme by [3H]FSBI is estimated to proceed with modification of 0.8 mol of beta-Tyr-345/mol of enzyme. Another notable observation is that inosine triphosphatase (ITPase) activity catalyzed by F1 from bovine heart mitochondria is much more sensitive to inactivation by 5'-p fluorosulfonylbenzoyladenosine (FSBA) than is ATPase activity. Whereas complete inactivation of ATPase activity by FSBA has been shown to proceed with the mutually exclusive modification of Tyr-368 or His-427 in all three copies of the beta subunit (Bullough, D. A., and Allison, W. S. (1986) J. Biol. Chem. 261, 5722 5730), it is shown here that complete inactivation of ITPase activity by FSBA is accompanied by modification of these residues in only one copy of the beta subunit. Inactivation of both the ATPase and ITPase activities of the enzyme by FSBI proceeds with modification of Tyr-345 in a single copy of the beta subunit. PMID- 2876985 TI - Mechanism of calcium potentiation of oxygen free radical injury to renal mitochondria. A model for post-ischemic and toxic mitochondrial damage. AB - With a variety of forms of ischemic and toxic tissue injury, cellular accumulation of Ca2+ and generation of oxygen free radicals may have adverse effects upon cellular and, in particular, mitochondrial membranes. Damage to mitochondria, resulting in impaired ATP synthesis and diminished activity of cellular energy-dependent processes, could contribute to cell death. In order to model, in vitro, conditions present post-ischemia or during toxin exposure, the interactions between Ca2+ and oxygen free radicals on isolated renal mitochondria were characterized. The oxygen free radicals were generated by hypoxanthine and xanthine oxidase to simulate in vitro one of the sources of oxygen free radicals in the early post-ischemic period in vivo. With site I substrates, pyruvate and malate, Ca2+ pretreatment, followed by exposure to oxygen free radicals, resulted in an inhibition of electron transport chain function and complete uncoupling of oxidative phosphorylation. These effects were partially mitigated by dibucaine, a phospholipase A2 inhibitor. With the site II substrate, succinate, the electron transport chain defect was not manifest and respiration remained partially coupled. The electron transport chain defect produced by Ca2+ and oxygen free radicals was localized to NADH CoQ reductase. Calcium and oxygen free radicals reduced mitochondrial ATPase activity by 55% and adenine nucleotide translocase activity by 65%. By contrast oxygen free radicals alone reduced ATPase activity by 32% and had no deleterious effects on translocase activity. Dibucaine partially prevented the Ca2+-dependent reduction in ATPase activity and totally prevented the Ca2+-dependent translocase damage observed in the presence of oxygen free radicals. These findings indicate that calcium potentiates oxygen free radical injury to mitochondria. The Ca2+-induced potentiation of oxygen free radical injury likely is due in part to activation of phospholipase A2. This detrimental interaction associated with Ca2+ uptake by mitochondria and exposure of the mitochondria to oxygen free radicals may explain the enhanced cellular injury observed during post-ischemic reperfusion. PMID- 2876986 TI - Evidence for the presence of muscarinic acetylcholine receptors in bovine brain coated vesicles. AB - Evidence obtained from quinuclidinylbenzilate binding determinations suggested that muscarinic acetylcholine receptor molecules are present in purified bovine brain coated vesicles. Immunoprecipitates formed from coated vesicles with polyclonal antibodies to clathrin bound on the surface of fixed Staphylococcus aureus cells also showed quinuclidinylbenzilate binding activity. The high purity of coated vesicles was established by assays for biochemical markers and by electron microscopy. Muscarinic receptor sites for quinuclidinylbenzilate binding to coated vesicles displayed a Kd of 25 pM and a Bmax of about 191 fmol/mg of protein. Binding competition experiments using atropine, N-methylscopolamine, oxotremorine, and carbamylcholine confirmed the typical muscarinic nature of the binding site. Ranking order of potency for the receptors was: atropine greater than N-methylscopolamine greater than oxotremorine greater than carbachol Analysis of data using a two-site model revealed 13% high-affinity sites for oxotremorine, 66% high-affinity sites for carbachol, and 62% for the antagonist N methylscopolamine. Heterogeneity of binding affinities for muscarinic drugs detected in the coated vesicles may be related to the presence of coated vesicle subpopulations in brain tissue, (Kohtz, D. S., Kohtz, J. D., Schook, W. J., and Puszkin, S. (1985) J. Cell Biol. 101, 48a; Pfeffer, S. R., and Kelly, R. B. (1985) Cell 40, 949-957). PMID- 2876987 TI - Localization of a liver transglutaminase and a large molecular weight transglutaminase substrate to a distinct plasma membrane domain. AB - Rat liver plasma membranes contain transglutaminase activity and a large molecular weight protein aggregate that serves as a substrate for this enzyme (Slife, C.W., Dorsett, M.D., Bouquett, G.T., Register, A., Taylor, E., and Conroy, S. (1985) Arch. Biochem. Biophys. 241, 329-336; Slife, C.W., Dorsett, M.D., and Tillotson, M.L. (1986) J. Biol. Chem. 261, 3451-3456). When purified plasma membranes were sonicated and the different plasma membrane domains were separated by sedimentation through a linear sucrose gradient, virtually all of the transglutaminase activity and the large molecular weight transglutaminase substrate were associated with membrane fragments which migrated to a very dense region of the gradient (1.18 g/cm3). The bile canalicular markers, 5' nucleotidase and HA-4 antigen, were predominantly found at 1.11 g/cm3, while most of the sinusoidal/lateral marker, CE-9 antigen, was detected at 1.14 g/cm3. Smooth membrane vesicles were observed chiefly at the lighter densities upon morphological analysis, while many filament-bearing, plasma membrane segments and junctional complexes were contained in the heavy transglutaminase fractions. These data show that the plasma membrane transglutaminase and the large molecular weight transglutaminase substrate are associated with a distinct region of the plasma membrane. PMID- 2876988 TI - Reconstitution of mitochondrial F0.F1-ATPase with phosphatidylcholine using the nonionic detergent, octylglucoside. AB - A reconstitution procedure has been developed for the incorporation of the mitochondrial F0.F1-ATPase into the bilayer of egg phosphatidylcholine vesicles. The nonionic detergent, octylglucoside, egg phosphatidylcholine, and the lipid deficient, oligomycin-sensitive F0.F1-ATPase (Serrano, R., Kanner, B., and Racker, E. (1976) J. Biol. Chem. 251, 2453-2461) were combined in a 4770:320:1 detergent/phospholipid/protein molar ratio and then centrifuged on a discontinuous sucrose gradient to isolate the F0.F1-phosphatidylcholine complex. The specific activity of the reconstituted F0.F1-ATPase was as high as 14.5 mumol/min/mg protein, whereas with no added lipid the activity ranged between 1.4 and 2.2 mumol/min/mg protein. This reconstituted preparation exhibited greater than 90% oligomycin sensitivity which demonstrated the intactness of the multisubunit enzyme complex. The phosphatidylcholine/protein molar ratio of the reconstituted F0.F1 was 250:1 with less than 0.4% of the added octylglucoside remaining. Titrations with both phosphatidylcholine and octylglucoside demonstrated that the specific activity and oligomycin sensitivity were highly dependent on the concentrations of both phospholipid and detergent in the original reconstitution mixture. Analysis of the reconstituted ATPase by electron microscopy demonstrated that the catalytic portion of the enzyme complex projected from the phospholipid bilayer with an orientation similar to that observed with submitochondrial particles. The F0.F1-phosphatidylcholine complex was able to trap inulin, which suggests a vesicular structure impermeable to macromolecules. The electrophoretic mobility of the complex was identical to that for liposomes of egg phosphatidylcholine alone. The reconstitution conditions utilized give rise to an enzyme-phospholipid complex with very low ionic charge that demonstrates high oligomycin-sensitive ATPase activity. PMID- 2876989 TI - Effect of phospholipids on the catalytic subunits of the mitochondrial F0.F1 ATPase. AB - Beef heart mitochondrial F0.F1-ATPase was reconstituted into phospholipid liposomes using the octylglucoside solubilization, discontinuous sucrose gradient centrifugation procedure described in the preceding manuscript (Laird, D., Smith Eble, K., and Cunningham, C. (1986) J. Biol. Chem. 261, 14844-14850). The influence of individual phospholipids (phosphatidylcholine (PC), phosphatidylethanolamine (PE), and diphosphatidylglycerol (DPG)) on the kinetic parameters related to ATPase activity were investigated. The specific activities for the PC, PE, and DPG reconstituted preparations were 9.8, 6.8, and 7.6 mumol of ATP hydrolyzed per min/mg of protein, respectively. The F0.F1-DPG complex demonstrated a 40% decrease in the Km for ATP. Both the F0.F1-PC and the F0.F1-PE complexes exhibited Ki values for adenyl-5'-yl imidodiphosphate and guanyl-5'-yl imidodiphosphate approximately 2.5 times lower than those obtained in the absence of exogenous phospholipid. The F0.F1-DPG complex displayed Ki values 11.7- and 1.8-fold lower for adenyl-5'-yl imidodiphosphate and guanyl-5'-yl imidodiphosphate, respectively, as compared to the lipid-depleted enzyme. The phospholipids with which F0.F1 were reconstituted also influenced the ATP-induced decrease in the fluorescence of enzyme-associated aurovertin. The rate of the ATP elicited decrease in aurovertin fluorescence was accelerated in the presence of all three phospholipids with DPG having the most dramatic effect; the t1/2 for maximal decrease in aurovertin fluorescence was 4.3 s for lipid-deficient enzyme and 0.48 s with the F0.F1-DPG complex. The effects of phospholipids on these parameters associated with the catalytic center of the ATPase suggest that phospholipids can modulate catalytic events occurring in F1. In the intact mitochondrion the primary role of phospholipids may be to stabilize conformations of the enzyme consistent with its range of activities. PMID- 2876990 TI - Receptor-mediated activation of spermatozoan guanylate cyclase. AB - The sea urchin egg peptides speract (Gly-Phe-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly) and resact (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Arg-Leu-NH2) bind to spermatozoa of the homologous species (Lytechinus pictus or Arbacia punctulata, respectively) and cause transient elevations of cyclic GMP concentrations (Hansbrough, J. R., and Garbers, D. L. (1981) J. Biol. Chem. 256, 1447-1452). The addition of these peptides to spermatozoan membrane preparations caused a rapid and dramatic (up to 25-fold) activation of guanylate cyclase. The peptide-induced activation of guanylate cyclase was transient, and the subsequent decline in enzyme activity coincided with conversion of a high Mr (phosphorylated) form of guanylate cyclase to a low Mr (dephosphorylated) form. When membranes were incubated at pH 8.0, the high Mr form was converted to the low Mr form without substantial changes in basal enzyme activity. However, the peptide-stimulated activity of the low Mr form of guanylate cyclase was much less than the peptide stimulated activity of the high Mr form. Activation of the low Mr form by peptide was not transient and persisted for at least 10 min. In addition, the pH 8.0 treatment that caused the Mr conversion of guanylate cyclase also caused an increase in the peptide-binding capacity of the membranes. We propose a model in which activation of the membrane form of guanylate cyclase is receptor-mediated; the extent of enzyme activation is modulated by its phosphorylation state. PMID- 2876991 TI - Conformation-specific antiserum raised against subunit c of ATP synthase (F1F0) from Escherichia coli. AB - Subunit c of the membrane-integrated, proton-translocating F0 portion of the ATP synthase (F1F0) from Escherichia coli has been isolated under nondenaturing conditions (Schneider, E., and Altendorf, K. (1985) EMBO J. 4, 515-518) and antibodies have been raised in rabbits. The primary antisera did not recognize the antigen when present in the same buffer as used for the immunization. Surprisingly, in one of the three antisera a strong antibody binding was observed when intact F0, a.c complex or reconstituted subunit c was provided as the antigen. Incorporation of subunit c into liposomes together with subunits a and b forming an active, H+-translocating complex was not required for the recognition by the antiserum. Subunit c prepared by chloroform/methanol extraction or by chromatography in the presence of sodium dodecyl sulfate was not recognized by the anti-c antiserum when incorporated into liposomes. PMID- 2876993 TI - Pertussis toxin inhibits retinoic acid-induced expression of tissue transglutaminase in macrophages. AB - Retinoic acid rapidly induces the accumulation of a specific enzyme, tissue transglutaminase (EC 2.3.2.13), in mouse macrophages. We have used the induction of tissue transglutaminase to study the regulation of gene expression by retinoic acid. In this study we report that pertussis toxin can inhibit retinoic acid induced expression of tissue transglutaminase in mouse resident peritoneal macrophages. This inhibition is paralleled by the ADP-ribosylation of 41,000 dalton macrophage membrane protein. PMID- 2876992 TI - Primary structure of the Neurospora plasma membrane H+-ATPase deduced from the gene sequence. Homology to Na+/K+-, Ca2+-, and K+-ATPase. AB - The gene for the Neurospora crassa plasma membrane H+-ATPase has been cloned and sequenced. The gene encodes for a protein of 920 amino acids with a molecular weight of 100,002. The coding region is interrupted by four introns: three near the amino terminus and one near the carboxyl terminus. The deduced amino acid sequence of the N. crassa plasma membrane H+-ATPase exhibits 75% homology to the amino acid sequence of the Saccharomyces cerevisiae plasma membrane H+-ATPase. Also, an amino acid comparison with the Na+/K+-ATPase from sheep kidney, Ca2+ ATPase from rabbit muscle, and K+-ATPase from Escherichia coli reveals that certain regions are highly conserved and suggest that these regions may serve essential functions which are common to the various cation-motive ATPases. This observation suggests that the phosphorylatable, cation-motive ATPases may function via a similar energy transduction mechanism. PMID- 2876994 TI - Characterization of transglutaminase activity in rabbit tracheal epithelial cells. Regulation by retinoids. AB - Rabbit tracheal epithelial cells undergo terminal cell division, start to express a squamous phenotype, and form cross-linked envelopes when reaching the plateau phase of the growth curve. This terminal differentiation is accompanied by a 20 30-fold increase in the activity of the cross-linking enzyme transglutaminase. This activity is found almost solely in the particulate fraction of homogenized cells and can be solubilized by nonionic detergents. This transglutaminase crossreacts with a monoclonal antibody raised against type I transglutaminase, but does not react with an antiserum against type II transglutaminase. The tracheal transglutaminase contains a protein subunit of approximately 92 kDa. The omission of epidermal growth factor from the medium or the addition of fetal bovine serum, conditions that induce terminal cell division and expression of a squamous phenotype, enhance transglutaminase activity. High calcium concentrations only stimulate transglutaminase activity after the cells become committed to terminal cell division. Retinoids, which inhibit the expression of the squamous phenotype but not terminal cell division, inhibit the enhancement in transglutaminase activity induced by either confluency or serum, indicating that this enzyme activity is under the control of retinoids. Some retinoids are active at concentrations as low as 10(-12) M. The ability of retinoids to inhibit transglutaminase activity correlates well with their capacity to bind to the retinoic acid-binding protein. Our results show that the increase in transglutaminase activity correlates with the induction of the terminal differentiated phenotype and suggest that this enzyme can function as a marker for this program of differentiation of rabbit tracheal epithelial cells in culture. Our results identify the transglutaminase as type I transglutaminase and are in agreement with the concept that this transglutaminase is involved in the formation of cross-linked envelopes. PMID- 2876996 TI - Calcium antagonists and sympathetic neuroeffector function. PMID- 2876995 TI - Nuclear genes encoding the yeast mitochondrial ATPase complex. Analysis of ATP1 coding the F1-ATPase alpha-subunit and its assembly. AB - Mitochondria prepared from the yeast nuclear pet mutant N9-84 lack a detectable F1-ATPase activity. Genetic complementation of this mutant with a pool of yeast genomic DNA in the yeast Escherichia coli shuttle vector YEp13 restored its growth on a nonfermentable carbon source. Mitochondria prepared from the transformed host contained an 8-fold higher than normal level of the F1 alpha subunit and restored ATPase activity to 50% that of the wild-type strain. Deletion and nucleotide sequence analysis of the complementing DNA on the plasmid revealed a coding sequence designated ATP1 for a protein of 544 amino acids which exhibits 60 and 54% direct protein sequence homology with the proton translocating ATPase alpha-subunits from tobacco chloroplast and E. coli, respectively. In vitro expression and mitochondrial import experiments using this ATP1 sequence showed that additional amino-terminal sequences not present in the comparable plant and bacterial subunits function as transient sequences for import. PMID- 2876997 TI - [Prosthesis failures due to the weakness of soldered joints]. PMID- 2876998 TI - [Metal migration of the elements of base alloys, in the liquid phase, during soldering]. PMID- 2876999 TI - Cotranslational and posttranslational proteolytic processing of preprosomatostatin-I in intact islet tissue. AB - Preprosomatostatin-I (PPSS-I) is processed in anglerfish islets to release a 14 residue somatostatin (SS-14). However, very little is known regarding other processing events that affect PPSS-I. This is the first study to identify and quantify the levels of nonsomatostatin products generated as a result of processing of this somatostatin precursor in living islet tissue. The products of PPSS-I processing in anglerfish islet tissue were identified in radiolabeling studies using a number of criteria. These criteria included immunoreactivity, specific radiolabeling by selected amino acids, radiolabel sequencing, and chromatographic comparison to isolated, structurally characterized fragments of anglerfish PPSS-I using reverse-phase high performance liquid chromatography. Intact prosomatostatin-I (aPSS-I) was isolated from tissue incubated with [3H]tryptophan and [14C]leucine. Significant 14C radioactivity was observed in the products of 11 of the first 44 sequencer cycles in positions consistent with the generation of a 96-residue prosomatostatin. These results indicate that signal cleavage occurs after the cysteine located 25 residues from the initiator Met of PPSS-I, resulting in a signal peptide 25 amino acids in length. Nonsomatostatin-containing fragments of the precursor were also found in tissue incubated with a mixture of 3H-amino acids. Only a small quantity of the dodecapeptide representing residues 69-80 in the prohormone was found (10 nmol/g tissue). Two other fragments of aPSS-I, also observed to be present in low abundance, were found to correspond to residues 1-27 (16 nmol/g tissue) and to residues 1-67 (7 nmol/g tissue) of aPSS-I. No evidence for the presence of the fragment corresponding to residues 29-67 was found. However, large quantities of SS-14 were observed (287 nmol/g tissue), indicating that the major site of aPSS-I cleavage is at the basic dipeptide immediately preceding SS-14. Recovery of much lower levels of the nonsomatostatin fragments of aPSS-I suggests that prohormone processing at the secondary sites identified in this study occurs at a low rate relative to release of SS-14 from aPSS-I. PMID- 2877001 TI - Stepped-care therapy for angina pectoris? PMID- 2877002 TI - The immunology of idiopathic inflammatory bowel disease. PMID- 2877003 TI - Radioiodination of somatostatin analogues employing Sep-Pak rapid sample purification and label assessment by high-performance liquid chromatography. PMID- 2877000 TI - Microtubule polarity confers direction to pigment transport in chromatophores. AB - The cellular mechanisms used to direct translocating organelles are poorly understood. It is believed that the intrinsic structural polarity of microtubules may play a role in this process. We have examined the effects that differently oriented microtubules have upon the direction of pigment transport in surgically severed melanophore arms. In a previous paper (McNiven, M. A., M. Wang, and K. R. Porter, 1984, Cell, 37:753-765) we reported that after isolation, arms repolarized and reoriented their microtubules outward from their centers as if to form new "microcells." Pigment aggregation in these arms was toward a new focal point located at the arm centers. In this study we monitored pigment movement in isolated arms containing taxol-stabilized microtubules to test if the reversal in direction of pigment transport is dependent upon the repolarization of microtubules. We report that taxol delays both the microtubule reorientation and reversal in transport direction in a concentration-dependent manner. These and other presented data suggest that the polarity of the microtubule population within a melanophore confers direction on pigment transport. PMID- 2877004 TI - Isolation of dengue viruses by intracerebral inoculation of mosquito larvae. AB - The isolation of dengue viruses from clinical specimens has always posed a particularly difficult problem. The use of invertebrate cell cultures such as AP 61 and C6/36 has reduced the time required for definitive diagnosis to within a week. More recently, inoculation of adult mosquitoes has been used but it requires more than a week to reach a confirmed laboratory diagnosis. We describe a method using intracerebral inoculation of immobilized fourth instar of Toxorhynchites splendens larvae for the isolation of dengue viruses from clinical specimens which yields results within a few days following incubation at 32 degrees C. PMID- 2877005 TI - Enzyme-linked immunosorbent assay for adherence of bacteria to animal cells. AB - Epithelial cells scraped from human oral mucosa and from pig intestines were immobilized onto the flat bottom surfaces of microtiter plates to study the adherence of various bacterial species to host cells. Bacterial adherence was quantitated either by an enzyme-linked immunosorbent assay technique with specific antibacterial serum as the first antibody followed by peroxidase conjugated second antibody or by using biotinylated bacteria and avidin peroxidase as the detecting agent. Unlabeled Escherichia coli and purified E. coli 987P fimbriae inhibited the adherence of biotinylated E. coli to immobilized enterocytes. The adherence of a mannose-sensitive strain of E. coli to immobilized oral epithelial cells was inhibited by mannose derivatives. The adherence of fimbriated E. coli 987P to immobilized enterocytes was approximately four times higher than the adherence of a nonfimbriated variant of the same strain. The adherence of Streptococcus pyogenes to oral cells was detected in the range of 10 to 150 bacteria per cell and was inhibited by lipoteichoic acid and albumin. The data suggest that the putative receptors which bind bacteria on the immobilized cells retain a functional form similar to that of native cells in suspension. The proposed adherence assay is easy to perform, allows the detection of specific adherence of test bacteria, and provides objective quantitation of adherence with a sensitivity of 10 bacteria per cell. Most importantly, the assay allows the testing of many variables in the same day. PMID- 2877006 TI - Prevalence of enteric parasites in homosexual patients attending an outpatient clinic. AB - A total of 372 pooled stool specimens from 274 homosexual men with diarrhea were submitted for parasitologic examination over a 2.5-year period. Each two-vial pooled specimen set contained portions of stool from 3 consecutive days in Formalin and polyvinyl alcohol. Of the 274 patients, 133 (48.5%) harbored one or more intestinal protozoa, with 161 (43.3%) of the 372 specimens submitted being positive for one or more organisms. The parasites identified included Entamoeba histolytica (71 patients), Giardia lamblia (22 patients), Endolimax nana (106 patients), Entamoeba coli (39 patients), Entamoeba hartmanni (25 patients), Dientamoeba fragilis (3 patients), Iodamoeba butschlii (2 patients), and Chilomastix mesnili (2 patients). Cryptosporidium sp. (2 patients) and Isospora belli (1 patient) were also detected. Results of this study support the experience of other workers regarding high rates of infection with intestinal parasites in the homosexual population and also indicate that symptomatic individuals belonging to this acquired immunodeficiency syndrome risk group be screened for both common and uncommon intestinal pathogens. PMID- 2877007 TI - Comparison of immunofluorescence and hemagglutination inhibition tests and enzyme linked immunosorbent assay for detection of serum antibody in rats infected with hemorrhagic fever with renal syndrome virus. AB - Serum antibodies against the B-1 strain of hemorrhagic fever with renal syndrome (HFRS) virus in wild and experimental rats were investigated by the indirect immunofluorescent antibody (IF) test, the hemagglutination inhibition (HI) test, and an enzyme-linked immunosorbent assay (ELISA). In the newly developed ELISA, monoclonal antibodies to the B-1 strain were applied as coating antibody. In sera from wild rats, the results obtained by the ELISA agreed quite well with those obtained by the HI test, but some serum samples that gave a negative reaction in the HI test gave a positive reaction in the IF test, although their IF titers were very low. In serum samples from experimental rats that had been kept in an animal house infected with HFRS virus, a group with high titers and a group with low or negative titers were clearly differentiated by all the tests. PMID- 2877009 TI - Etiological agent and primary source of infection in 42 cases of focal intracranial suppuration. AB - The microbiological findings for 42 patients with focal intracranial suppuration were analyzed and correlated with the different sources of primary infection. Streptococcus spp. were identified in focal intracranial suppuration of all origins except postcraniotomy. Microaerophilic streptococci were important in cases secondary to respiratory tract infection and in those of unknown origin. Streptococcus faecalis, Proteus spp., and Bacteroides fragilis were the organisms most commonly found in polymicrobial otogenic abscesses. Clostridium sp. was the main microorganism implicated in postcraniotomy suppurations. PMID- 2877008 TI - Virulence characteristics of Aeromonas spp. in relation to source and biotype. AB - The significance of Aeromonas spp. as potential water-borne enteric pathogens in Tasmania, Australia, an area with a mild climate and comparatively low year-round water temperatures, was investigated in view of the reported marked peak of Aeromonas-associated gastroenteritis in the summer and the apparent influence of temperature on levels of potentially pathogenic species in water supplies. Biochemical characteristics and virulence-associated properties--exotoxin production (hemolysin, enterotoxin), ability to grow at 43 degrees C, and possession of pili--were determined for 105 Tasmanian isolates of Aeromonas spp.; 43 isolates were from clinical specimens (greater than 75% diarrhea associated) and 62 were from water. Current classification schemes were evaluated for these isolates. A. sobria comprised 35% of the clinical isolates and 16% of the water isolates, A. hydrophila comprised 56 and 79%, and A. caviae comprised 9 and 5%. A total of 42% of the clinical isolates and 15% of the environmental isolates were enterotoxigenic (by the suckling mouse assay); these levels were significantly lower than those found in warmer environments. The majority (74%) of enterotoxigenic isolates were A. sobria. Enterotoxin-producing isolates possessed three or more of the following properties. They were Voges-Proskauer positive, did not hydrolyze arabinose, were positive for lysine decarboxylase, were able to grow at 43 degrees C, and produced large amounts of hemolysin (titer, greater than 128). Thus, the biochemical scheme proposed by Burke et al. (V. Burke, J. Robinson, H.M. Atkinson, and M. Gracey, J. Clin. Microbiol. 15:48-52, 1982) for identifying enterotoxigenic isolates appears to have widespread applicability. Environmental enterotoxigenic isolates possessed numerous pili, but these appeared to be lost once infection was established, as a similar isolates from patients with diarrhea were poorly piliated. PMID- 2877010 TI - Lack of direct inhibition of insulin secretion by exogenous insulin in the canine pancreas. AB - To test whether insulin secretion is self-regulatory, canine pancreata were isolated and perfused in vitro and were infused with 0.3, 0.6, or 1.2 mU/ml exogenous insulin. Basal and arginine-stimulated concentrations of C-peptide, glucagon, and somatostatin were measured. There were no significant differences between basal secretion nor the increment of arginine-stimulated secretion for each respective hormone at each exogenous insulin concentration. The second preparation studied was a vascularly isolated, yet innervated, in situ perfused pancreas. Exogenous insulin (1 mU/kg per min) was infused "systemically"; the pancreas received no insulin. Endogenous pancreatic insulin and C-peptide secretion was suppressed, while pancreatic glucagon secretion increased during systemic insulin infusion. No changes in pancreatic hormone secretion occurred after the sympathetic nerves were sectioned. These results suggest that exogenous insulin does not directly suppress the B cell, but can suppress insulin secretion through an indirect neurally mediated, insulin-dependent nerve mechanism. PMID- 2877012 TI - Neuroleptic malignant syndrome: a review of the literature. AB - The neuroleptic malignant syndrome (NMS) involves fever, extrapyramidal rigidity, and disturbances of autonomic function and consciousness. It occurs more often with high potency and depot forms, frequently 3 to 9 days after initiation and sometimes years later, and is not related to dose or previous exposure. About 40% of cases had evidence of an affective disorder. NMS apparently results from deficient compensatory mechanisms following blockade of dopaminergic regulation of muscle tone and autonomic function. Possible indicators of vulnerability and various treatments are discussed. Neuroleptic challenge resulted in recurrence of symptoms in about one third of cases. Symptoms sometimes subsided despite continued treatment. Early diagnosis and effective treatment have reduced the risk of such challenge. PMID- 2877011 TI - Infection of human T lymphotropic virus-I-specific immune T cell clones by human T lymphotropic virus-I. AB - Human T lymphotropic virus-I (HTLV-I)-specific T cell lines were established and cloned. K5, an OKT8+ clone bearing multiple proviral integration sites, retained its HTLV-I-specific cytotoxicity and a normal dependence on interleukin 2 (IL-2), indicating that there is a finite number of transforming integration sites. R2, an OKT4+ HTLV-I-infected clone, initially mounted a proliferative response to HTLV-I; but then its IL-2-independent proliferation increased and the antigen specificity was lost. All HTLV-I-infected clones tested including K7, another OKT8+ transformed cytotoxic clone that had lost its reactivity, expressed comparable levels of T cell receptor beta-chain (TCR-beta) messenger (m)RNA. Although clones K5 and K7 had different functional properties, they had the same rearrangement of the TCR-beta gene, suggesting that they had the same clonal origin. These data indicate that HTLV-I-specific T cells retain their immune reactivity for variable periods of time following infection, but then usually lose it; in some cases, however, no alteration in function can be detected. The data also suggest that different consequences can take place in the same clone depending on the pattern of retroviral infection. PMID- 2877013 TI - Occurrence of human T cell lymphotropic virus (type I) antibodies in cutaneous T cell lymphoma. AB - Of 315 patients from Scandinavia and West Germany with cutaneous T cell lymphoma, thirty-six (11.4%) had specific antibodies reactive against human T cell lymphotropic virus type I (HTLV-I). Among the HTLV-I antibody-positive patients, one had Sezary syndrome; five, mycosis fungoides, plaque stage; sixteen, mycosis fungoides, plaque stage with nondiagnostic histologic features; and three, lymphomatoid papulosis. All the patients from the Copenhagen area had several samples taken during the course of their disease, but the HTLV-I antibody titer was unaltered independent of the clinical stage the individual patient had at the time of the study. Eighty-three patients with non-Hodgkin's lymphoma were tested for HTLV-I antibodies, and all except two showed negative results. The finding of specific antibodies reactive against HTLV-I in cutaneous T cell lymphoma suggests that a retrovirus related to HTLV-I plays an important role in the pathogenesis of cutaneous T cell lymphoma. PMID- 2877014 TI - Cutaneous polyarteritis nodosa associated with hepatitis B surface antigen. AB - The finding of hepatitis B surface antigen in systemic polyarteritis nodosa is well recognized. We described a case of cutaneous polyarteritis nodosa associated with hepatitis antigenemia and a medium-sized vessel vasculitis on skin biopsy, with no evidence of systemic involvement. PMID- 2877015 TI - Therapeutic consequences of drug interactions with theophylline pharmacokinetics. AB - Elimination of theophylline from the body occurs mainly (approximately 90%) by biotransformation, followed by excretion of the metabolites. Consequently, drugs affecting microsomal enzyme systems in the liver may alter the elimination of theophylline. Since theophylline has a rather narrow therapeutic window, dose adjustment might be necessary. Of the sympathomimetics, isoproterenol reduces theophylline clearance by 25%, but metaproterenol and terbutaline do not. Of the antibiotics, erythromycin and troleandomycin decrease theophylline clearance by 25% and 50%, respectively. No effect was observed with tetracycline, doxycycline, amoxicillin, cefaclor, and co-trimoxazole. On the other hand, rifampin (antituberculotic agent) increases theophylline clearance by 30%. Corticosteroids (hydrocortisone, methylprednisolone, and prednisone) do not affect theophylline kinetics. Influenza vaccination also has no influence. The antiulcerative agent (H2 antagonist) cimetidine decreases theophylline clearance by 30%, but the agent ranitidine does not have any effect. Oral contraceptives may decrease theophylline elimination by 30%. Barbiturates and phenytoin may enhance theophylline clearance substantially (up to 75%). If an interaction is expected, careful monitoring of theophylline plasma concentrations is required to optimize the dose. PMID- 2877016 TI - Overview of effects of theophylline. AB - Ever since xanthines were introduced into asthma therapy, more than 125 years ago, their therapeutic effectiveness has been explained as being due to extrapulmonary rather than, or in addition to, pulmonary drug actions. This article emphasizes that theophylline may have several potentially important effects in the lung. Theophylline relaxes the smooth muscle of large and small airways in humans and animals. Its relaxant effect is relatively independent of the type of mediator that constricts the airway. This suggests that functional antagonism, rather than specific pharmacologic mediator antagonism (e.g., adenosine antagonism), explains its bronchodilator effect. The consistent relaxant property of such xanthines as theophylline distinguishes these compounds from many other classes of established and experimental bronchodilator agents. Furthermore, many anti-inflammatory effects have been noted, suggesting that xanthines might be considered as prophylactic agents. Theophylline may not only attenuate the activity of stationary and blood-borne pulmonary inflammatory cells; it may also exert an anti-inflammatory action by directly affecting targets such as the epithelial lining (increasing the mucociliary transport rate) and the microvasculature (possibly reducing plasma exudation). The experimental anti-inflammatory pharmacology of theophylline is compatible with the observation that theophylline inhibits late pulmonary reactions in patients with atopic asthma and in sensitized animals challenged with allergen. The mechanism(s) of action behind the pulmonary actions of theophylline has not been assessed (neither phosphodiesterase inhibition nor adenosine antagonism may be involved). Central nervous system, gastroesophageal, renal, and metabolic actions of theophylline are briefly reviewed. Headache, nausea, and the relaxation of the lower esophageal sphincter can perhaps be classified as nonexcitatory and inhibitory effects in which the mechanism(s) of action is unknown.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877017 TI - Theophylline in chronic obstructive pulmonary disease. AB - Although prolonged use of maintenance theophylline therapy in chronic obstructive lung disease remains controversial, evidence from well-designed studies indicates that it produces patient improvement as gauged by both objective and subjective measurements. An important reason to use sustained-release theophylline is to prevent episodes of bronchospasm by providing a smooth around-the-clock bronchodilator effect and thus reducing the need for periodic aerosolized beta agonists. Theophylline also increases diaphragmatic contractility and endurance, although there is disagreement concerning the practical clinical significance of this effect. The drug improves cardiovascular function by increasing myocardial contractility and by reducing pulmonary and systemic vascular resistances. The increased central respiratory drive produced by theophylline may be important in reducing the ventilatory depressant effects of oxygen therapy. The drug also acts to inhibit mediator release and improves several aspects of mucociliary function, although, again, the clinical significance of these actions has not been established. PMID- 2877018 TI - Adverse effects of theophylline-beta agonist interactions. AB - Beta-adrenergic agonists, when administered alone or concomitantly with methylxanthines are capable of producing lesions of myocardial necrosis and an increased incidence of cardiac arrhythmias in several species of animals. These drugs, including "beta 2-specific" agonists, also have the potential to produce adverse cardiovascular effects when used clinically. In addition, beta agonists and methylxanthines can interact to potentiate or lessen effectiveness and theoretically increase the risk to the patient. As a result, the extent to which the concomitant administration of these drugs may contribute to adverse clinical effects needs further clarification. PMID- 2877019 TI - Investigation of catecholamine effects on stomach and duodenum motor functions in unanaesthetized dogs. AB - The aim of this study was to investigate the effects of catecholamines on motility of stomach and intestine in chronic experiments on dogs with fistulas in stomach and duodenum. The contractions of stomach and duodenum were registered by a balloon method. It was established that i.v. adrenaline and noradrenaline injections in dogs with intact vagi inhibited food-induced motility in stomach and duodenum and did not produce contractions in the empty and quiescent gastrointestinal tract. Beta-adrenoagonist isoprenaline on the contrary produced stomach and duodenum contractions in fed dogs during the quiescent period. In fed dogs isoprenaline caused a 3-phasic reaction: a phase of primary short-term suppression of stomach and duodenum motility, a phase of motility increase and a phase of secondary suppression of stomach and duodenum motility. The contractions evoked by isoprenaline in the stomach resemble in amplitude and shape, periodical activities which are typical for fasting dogs. Vagotomy intensified isoprenaline motor effects in hungry and fed dogs and eliminated the phase of primary suppression in fed dogs. The isoprenaline effects were blocked by propranolol, but not by phentolamine. They were decreased more effectively in the stomach by atropine and by hexomethonium in the duodenum. PMID- 2877020 TI - Autonomic nervous control of the endocrine secretion from the isolated, perfused pig pancreas. AB - The effect of electrical stimulation of the splanchnic and the vagus nerve supply to isolated, perfused pig pancreas on the secretion of insulin, glucagon and pancreatic polypeptide (PP) was investigated. Functional integrity of the autonomic nerve supply was assessed by the effect of nerve stimulation on vascular resistance and exocrine secretion. Splanchnic nerve stimulation increased glucagon and PP output (2 to 3-fold) and inhibited insulin output (by 42%). Propranolol abolished the effect on PP and glucagon secretion, but did not affect the inhibition of insulin secretion. Phenoxybenzamine abolished the inhibition of insulin secretion, reduced the effect on glucagon secretion and enhanced the effect on pancreatic polypeptide secretion. Combined alpha- and beta adrenergic blockade abolished all effects of splanchnic nerve stimulation. Vagus nerve stimulation increased the secretion of all 3 hormones (PP: up to 30-fold, insulin and glucagon: 3 to 5-fold). The effect on insulin and PP-secretion was mimicked by acetylcholine at 10(-7)-10(-6) M, whereas glucagon secretion was inhibited. The effect of vagus nerve stimulation on insulin and PP secretion was augmented by physostigmine, and inhibited (but not abolished) by atropine at 10( 7)-10(-6) M. The effect on glucagon secretion was inhibited by physostigmine and unaffected by atropine. It is concluded that all of the effects of splanchnic nerve stimulation on insulin and PP secretion can be explained by interactions of norepinephrine with excitatory beta-receptors on PP-cells and inhibitory receptors on the insulin cells. Both cell types are also stimulated via muscarinic cholinoceptors, but the partial atropine resistance suggests that other transmitters participate in vagal activation. The nervous regulation of glucagon secretion is complex and may involve the peptidergic innervation of the pancreatic islets. PMID- 2877021 TI - Video-enhanced technique for detecting neurophysin, enkephalin, and somatostatin immunoreactivity in ultrathin sections of cat median eminence. AB - A freeze-drying technique using epoxy-embedded ultrathin serial sections permits critical comparisons of neuropeptides in small fibers and varicosities of the nervous system by video-enhanced, light microscopic immunofluorescence. The desirability of the method was documented by data showing: retention of radioimmunoassayable somatostatin in freeze-substituted blocks of tissue as compared to its loss in tissue dehydrated in an alcohol series; feasibility of OsO4 vapor fixation of freeze-dried tissue and compatibility with neuropeptide immunocytochemistry, and utility of a silicon-intensified-tube video camera for recording low levels of fluorescence from ultrathin sections. Ultrathin serial sections, 150 nm thick, from the inner zone of freeze-dried median eminence of the cat revealed three populations of axons containing various combinations of neurophysin immunoreactivity and enkephalin immunoreactivity. Some elements contained neurophysin immunoreactivity alone, some contained both neurophysin immunoreactivity and enkephalin immunoreactivity, and a few elements contained enkephalin immunoreactivity alone. The adjacent external zone of the median eminence contained immunoreactivity for all three substances, but the structures in this region were too small to permit demonstration of coexistence in 150 nm thick sections. PMID- 2877022 TI - The use of gold-substituted silver-intensified diaminobenzidine (DAB) and non intensified DAB for simultaneous electron microscopic immunoperoxidase labeling of tyrosine hydroxylase and glutamic acid decarboxylase immunoreactivity in the rat medial preoptic area. AB - An improved gold-substituted silver intensification procedure for the peroxidase diaminobenzidine (DAB) reaction product was developed. The method was applied in the rat medial preoptic area to label tyrosine hydroxylase (TH)-immunoreactive profiles. Following the gold toning, the same sections were immunostained for glutamic acid decarboxylase (GAD) immunoreactivity with non-intensified peroxidase-DAB. Single DAB-labeled GAD axons were found in symmetric synaptic connection with unlabeled dendrites as well as with gold-toned immunoperoxidase containing TH neurons. PMID- 2877023 TI - DARPP-32 in the ciliary epithelium of the eye: a neurotransmitter-regulated phosphoprotein of brain localizes to secretory cells. AB - DARPP-32, a phosphoprotein enriched in dopaminoceptive brain neurons containing the D-1 receptor subtype, probably functions as an intracellular third messenger to mediate some of the physiological effects of dopamine at the D-1 receptor. By immunohistochemistry in rat, cat, Rhesus monkey, and human, we have localized DARPP-32 to the non-pigmented epithelium of the ciliary body, the innermost layer of the bi-layered epithelium responsible for secretion of aqueous humor into the eye. The immunoreactive protein in rat ciliary body, identified by immunolabeling of a ciliary body extract separated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis, is indistinguishable from DARPP-32 derived from rat caudatoputamen. By analogy with brain, we propose that DARPP-32 may act as a third messenger in the ciliary epithelium, probably through a dopaminergic mechanism. PMID- 2877024 TI - Nonspecific immunocytochemical reactions with certain neurohormonal peptides and basic peptide sequences. AB - Immunocytochemical staining experiments on filter paper or nitrocellulose models reveal that many, but not all, neurohormonal peptides, as well as poly-L-lysine, strongly bind a number of labeled reporter molecules, including colloidal gold- or peroxidase-labeled IgG, protein A, streptavidin, and albumin. Peptides displaying this type of (nonspecific) binding are basic; they include ACTH, VIP, opioid peptides, and poly-L-lysine. Pre-absorption of labeled probes with excess ACTH[1-24] or poly-L-lysine abolishes or greatly reduces binding not only to the homologous but also to the heterologous peptides tested. A number of cell types previously reported to display nonspecific immunoglobulin binding contain one or several of the basic neurohormonal peptides shown to display nonspecific absorption of labeled IgG, protein A, streptavidin, and albumin. This nonspecific absorption is reversed neither by high salt nor high pH conditions, nor by a number of detergents and blocking proteins. One dynorphin antiserum also displays nonspecific binding to the peptides as well as to pancreatic glucagon cells, and this nonspecific staining can be blocked by basic peptide pre-absorption (whether homologous or heterologous). These results suggest a need for caution when immunocytochemical studies of a number of basic polypeptides are interpreted, and also suggest the inclusion of novel control procedures in immunocytochemistry. PMID- 2877025 TI - Comparative study on the immunogenic properties of Clostridium perfringens type A toxoid. AB - The paper presents the results of a study on the immunogenic properties of toxoid preparations from Cl. perfringens type A obtained using the routine method of detoxifying alpha = toxin in the culture medium (commercial preparations) and by means of detoxifying a previously purified alpha = toxin (experimental preparations). When tested in immunized guinea pigs, the immunogenicity of experimental preparations was found to be 4.5 to 6 times that of commercial preparations. In mice, there was no difference in the immunogenic properties of the two types of preparations as determined by the ED30 of the antigen and the serum levels of Cl. perfringens antitoxin. The possibility is discussed of using the guinea pig as a laboratory animal model due to its ability to reflect most clearly the differences in the immunogenicity of Cl. perfringens type A toxoid preparations. PMID- 2877026 TI - Second messenger role of arachidonic acid and its metabolites in interferon-gamma production. PMID- 2877027 TI - Stimulatory effects of retinoic acid on macrophage interaction with blood forms of Trypanosoma cruzi: involvement of transglutaminase activity. AB - The effects of retinoic acid (RA; vitamin A acid) on macrophage function were investigated by measuring the capacities of mouse peritoneal macrophages to associate with (i.e., bind and internalize) and kill the unicellular parasite Trypanosoma cruzi. The presence of 10(-8) to 10(-6) M RA in co-cultures of macrophages and blood forms of the parasite markedly increased their interaction as evidenced by significant increases in both the percentage of phagocytes associating with parasites and the average number of parasites per 100 cells. A similar effect was produced when either the macrophages or the trypanosomes were pretreated with RA, suggesting that both cell types could contribute to the noted effect. Although RA might have enhanced parasite-macrophage association by binding to both, its ability to stimulate phagocytosis was independently evidenced by a significant increase in the uptake of latex particles. RA-treated macrophages also took up larger numbers of dead T cruzi, denoting that parasite viability (i.e., infectivity) was not necessary for the production of the RA effect. The minimum pretreatment time for RA to significantly stimulate macrophage association with T. cruzi was 30 min, although a 45-min pretreatment was necessary for a maximal effect to be seen under our experimental conditions. The RA effect was reversible because, once optimally induced, it remained demonstrable for only 30 to 60 min after removal of the reagent; however, the effect persisted for at least 3 hr if RA was not removed. Transglutaminase activity appeared to be involved in the RA effect, because the latter was abrogated when the macrophages were treated with RA in the presence of cystamine, methylamine, or monodansylcadaverine, all of which inhibit transglutaminase activity by different mechanisms. RA also increased the capacity of macrophages to kill parasites internalized before the treatment. This cytotoxic capacity was inhibited by catalase, indicating that H2O2 played a role in the killing mechanism. RA treatment significantly increased the proportion of macrophages capable of reducing nitroblue tetrazolium. The present results indicated that RA was capable of activating macrophages, leading to greater uptake and killing of a protozoan parasite. PMID- 2877028 TI - Assessment of multi-organ system engraftment by genotypic typing using restriction fragment-length polymorphisms and by phenotypic typing using a microcytotoxicity assay. AB - We report the first application of Southern blotting techniques for the quantitative assessment of the donor or host origin of cell populations present in recipients of allogeneic or sex-mismatched syngeneic murine donor marrow grafts. The sensitivity of this assay system was noted to 1 to 5% for detection of a minor cell population by using cDNA probes that hybridize to single-copy sequences in the murine genome. The use of probes that generate distinguishing autoradiographic patterns due to strain-specific genomic sequence variations obviates the need for retroviral vector transfections (which potentially skew engraftment quantitation). Southern blotting analysis has provided definitive engraftment data in multiple cell populations isolated from both short-term and long-term allogeneic and syngeneic radiation chimeras. In contrast, H-2 typing in a microcytotoxicity assay, a standard typing technique for allogeneic murine donor cell engraftment, was noted to be less sensitive than Southern blotting. This occurred particularly in selected cell populations, in ill-appearing recipients, and in the early post-BMT period. Furthermore, because H-2 typing is a phenotypic assay, the results may be substantially influenced by the passive cell surface acquisition of host H-2 antigens, a process that is not evident with the use of genotyping techniques. Our results establish the superiority of Southern blotting techniques for the quantitation of donor cell engraftment and demonstrate the potential of this methodology when low-level detection of engrafted donor or residual host cells is of critical physiologic importance. PMID- 2877029 TI - Depletion of cutaneous glutathione and the induction of inflammation by 8 methoxypsoralen plus UVA radiation. AB - The purpose of this study was to examine the dose response and time course relationships between PUVA (psoralen + UVA) depletion of skin glutathione (GSH) and the induction of inflammation. Dorsal skin fold thickness (DSFT), an index of cutaneous edema, was used as a noninvasive measure of inflammation. Ornithine decarboxylase (ODC) was used as a measure of epidermal damage. Female hairless mice were given 8-methoxypsoralen (8-MOP) (dissolved in corn oil) by gavage at different doses, and 2 h later the mice were irradiated with 5 J/cm2 UVA. At 24 h, DSFT measurements were taken, the mice were killed, and reduced GSH, glutathione disulfide (GSSG), and glutathione-S-transferase were measured in the epidermis and dermis. Epidermal GSH was depleted 0, 11, 45, 87, and 98% from vehicle and/or UVA-treated levels (0.7 mM) after 0.1, 0.5, 5, 25, and 50 mg/kg, respectively. In the dermis GSH decreased from 0.3 mM by 47, 87, and 91% after 5, 25, and 50 mg/kg 8-MOP, respectively. Increases in DSFT of 20, 141, and 242% were observed after 5, 25, and 50 mg/kg doses, respectively. GSSG accounted for a small portion of total GSH in the skin after PUVA treatment. The maximal decreases in GSH were not observed until 24-48 h after PUVA treatment. PUVA treatment leads to dose-related increases in dermal edema, epidermal ODC, and depletion of GSH levels from both compartments in the skin. The time course of glutathione loss suggests that PUVA may interfere with its resynthesis or utilization from the circulation. PMID- 2877030 TI - An erythematous maculopapular eruption in macaques infected with an HTLV-III-like virus (STLV-III). AB - A cutaneous maculopapular eruption has been previously described in humans infected with HTLV-III/LAV, the etiologic agent of acquired immunodeficiency syndrome. In this study, rhesus monkeys were prospectively examined after infection with an HTLV-III-like virus (STLV-III) to ascertain the incidence and clinical course of gross and histologic alterations of the skin. Between 1-3 weeks after inoculation, 83% of infected animals developed a transient cutaneous maculopapular eruption of the face, groin, and trunk. Histologically, the affected skin was characterized by a superficial perivascular infiltrate of mononuclear cells with associated endothelial cell hypertrophy and degeneration. This eruption preceded opportunistic infections, neoplasms, and other overt clinical signs commonly associated with an immunodeficiency syndrome. The findings suggest that STLV-III infection in the rhesus monkey closely simulates that which occurs in HTLV-III-infected individuals, and that the skin may represent a site of altered immunoregulation early in the course of this disease. PMID- 2877031 TI - Intrafamilial transmission of adult T cell leukemia virus. AB - In an investigation of the mode of transmission of adult T cell leukemia virus (ATLV) in family settings, 275 male and 444 female subjects positive for antibody to ATLV-associated antigen (anti-ATLA) were studied. Their children were surveyed for anti-ATLA status. None of the 82 children of a positive father and a negative mother were positive for anti-ATLA. In contrast, the antibody prevalence among children with a positive mother and a positive or negative father was 27.9% and 19.9%, respectively. Of 39 parents who had one or more anti-ATLA-positive children less than 20 years old, 56.3% of the fathers and 97.1% of the mothers were anti-ATLA positive. Algorithm computation showed the possibility of ATLV transmission from husband to wife to be 60.8% and from wife to husband to be 0.4% over a 10-year period. These data suggest that ATLV is transmitted from mother to child and from husband to wife in family settings. PMID- 2877032 TI - Unsuccessful use of praziquantel to treat acute fascioliasis in children. PMID- 2877033 TI - Basics of opioid analgesic pharmacodynamics. PMID- 2877034 TI - Unavailability of narcotic analgesics for ambulatory cancer patients in New York City. PMID- 2877035 TI - Narcotic analgesics: fears and responsibilities. PMID- 2877036 TI - Spinal opioid analgesics and local anesthetics in the management of chronic cancer pain. PMID- 2877037 TI - [Familial accumulation of anti-ATLA antibodies in an non-endemic area]. PMID- 2877038 TI - [Clinical features, laboratory data and anti-viral antibody titers in a severe case of hemorrhagic fever with renal syndrome (HFRS)--a one-month course from onset]. PMID- 2877039 TI - Neurological manifestations of acquired immunodeficiency syndrome. AB - This article provides an overview of the range of neurological manifestations that have been described in association with human immunodeficiency virus (HIV) infection. The transmission of acquired immunodeficiency syndrome (AIDS) and the precautions personnel must take when having contact with patients with AIDS are briefly reviewed. The nursing approach to the neurologically impaired victim of HIV infection is discussed. PMID- 2877040 TI - Anesthesiology in the 21st century: analgesic, sedative and anesthetic focusing. AB - The specialty of anesthesiology is on the verge of a major technological evolution (revolution) which will utilize the computative and logic powers of the computer as well as the recent and rapid advances in magnetic imaging and laser and drug receptor technology to introduce the concept of anesthetic drug focusing by the beginning of the next century. This will result in the need for only a few molecules of future anesthetic compounds because they will only be necessary at a limited number of receptors in a few neurons or nuclei in the brain and/or spinal cord. Analgesic, sedative and anesthetic action may not be dependent on any drug but rather be produced solely by a wave form or energy source focused via a computer on the appropriate receptors in the brain, spinal cord or peripheral nerves. Anesthetic drug focusing will enable anesthetic depth to be ideal, anesthetic action to be localized to only those cells, tissues or organs where it is desired and anesthetic onset and termination to be measured in micro-seconds. PMID- 2877041 TI - Serine proteases stimulate mucous glycoprotein release from hamster tracheal ring organ culture. AB - The effects of several neurohumoral agents and serine proteases on glycoconjugate release from hamster tracheal organ cultures were assessed. The beta-adrenergic agonist isoproterenol inhibited glycoconjugate release, and its effect was abolished by the specific beta-blocking agent propranolol. A cholinergic agonist, pilocarpine, marginally increased glycoconjugate release, and its effect was abolished by the antagonist atropine. Human neutrophil elastase and porcine pancreatic trypsin consistently increased glycoconjugate release by 1.8 to 2.8 fold. When the proteases were inactivated, they were no longer effective in stimulating glycoconjugate release. Histologic and electron microscopic analysis of the protease-treated organ cultures revealed no discernible toxic reaction. In addition, organ cultures prelabeled with chromium 51 did not release an increased amount of radioactivity when treated with the proteases. Biochemical analysis of the glycoconjugates released into the culture medium showed them to be of high molecular weight (90% eluted in the void volume of a Sepharose 6B column) and to be resistant to digestion with hyaluronidase and heparinase, properties consistent with mucous glycoproteins. The mechanism of protease-induced glycoconjugate release is unknown. We speculate that stimulation of airway secretory cells by serine proteases of neutrophilic or other inflammatory cell origin may play a role in the increased airway secretion that is characteristic of acute tracheobronchitis. PMID- 2877042 TI - Reaffirmation of the validity of enzymatic cleavage of lithocholic acid from N epsilon-lithocholyl-L-lysine and N-alpha-CBZ-N-epsilon-lithocholyl-L-lysine. AB - N-epsilon-lithocholyl-L-lysine or N-alpha-CBZ-N-epsilon-lithocholyl-L-lysine when incubated overnight at 37 degrees C with 3 K units of clostridial cholanoylaminoacid hydrolase (from Clostridium perfringens ATCC 19574) in the presence of disodium EDTA (0.1 M), beta-mercaptoethanol (0.1 M), and sodium acetate buffer, pH 5.6, released free lithocholic acid. The latter material was isolated by thin-layer chromatography and identified by combined gas-liquid chromatography-mass spectrometry in the full scan and selected-ion mode. In order to maintain its activity, the enzyme was always stored in 1.0-ml aliquots at temperatures below -20 degrees C and each aliquot when thawed was used immediately; any left over enzyme was never reused. Contrary to the observations of Yanagisawa et al. (J. Lipid Res. 1984. 25: 1263-1271) the results of this study reaffirm the validity of the original observations on the enzymatic cleavage of lithocholic acid from tissue-bound form. PMID- 2877043 TI - [Hemodynamic study, under hot and cold conditions, of the digital artery in arterial hypertension and the effects of cardioselective and non-cardioselective beta blocker treatment]. AB - The finger systolic pressure of 25 healthy subjects and 23 hypertensives was studied by plethysmography at 30 degrees, 15 degrees and 10 degrees centigrade. The hypertensive group was given equipotent doses of either Metoprolol or Propranolol in accordance with a double-blind cross-over protocol including a washout period. The fall in systolic pressure between the brachial artery in the upper arm and the digital artery was significantly increased in the hypertensive group as compared to healthy controls; the rise persisted under hot and hyperemic conditions and remained constant during both betablocker treatments. In the hypertensive group digital arterial tone increased under cold conditions before any treatment; this abnormality did not vary under Metoprolol but intensified significantly under Propranolol. Finger plethysmography made it possible to show and quantify the peripheral vascular repercussions of hypertension on the digital artery and evaluate the changes induced by treatments. It also helps to clarify the physiopathology of certain side effects caused by betablockers and might to some extent help in the choice and the survey of treatment and in the subsequent follow-up. PMID- 2877044 TI - [Microangiopathy and arterial hypertension in scleroderma and periarteritis nodosa]. AB - The mechanisms of blood pressure regulation in periarteritis nodosa and systemic sclerodermia are discussed in the light of results of personal studies. Hypertension during PAN may be divided into two groups: hypertension related to renal microangiopathy responsible for stimulation of the renin-angiotensin aldosterone system which often runs a severe course, sometimes accompanied by renal insufficiency and requiring treatment with beta-blocking agents or angiotensin conversion enzyme inhibitors; secondly, hypertension may not be linked to the renin-angiotensin-aldosterone system and the prognosis is then better. In systemic sclerodermia, a similar pattern may be found but it would also seem that the renin-angiotensin-aldosterone system may be stimulated in the absence of any hypertension. This rise in plasma renin activity and aldosterone preceding the onset of an acute sclerodermic renal episode has a very poor prognosis. Corticosteroid therapy may favour such a process. Other regulation mechanisms are also discussed: prostaglandins, bradykinin system. PMID- 2877045 TI - Seasonal variations in cryptorchidism. AB - The month of birth of boys undergoing orchidopexy in the Oxfordshire Health District during the years 1974-83 was analysed. A significant seasonal variation with a peak in April was found for those boys operated upon by paediatric surgeons at a young age (0-4). Possible causes of this variation and its relationship to the aetiology of cryptorchidism are discussed. PMID- 2877046 TI - Analysis of multiple restriction fragment length polymorphisms of the gene for the human complement receptor type I. Duplication of genomic sequences occurs in association with a high molecular mass receptor allotype. AB - Human CR1 exhibits an unusual form of polymorphism in which allotypic variants differ in the molecular weight of their respective polypeptide chains. To address mechanisms involved in the generation of the CR1 allotypes, DNA from individuals having the F allotype (250,000 Mr), the S allotype (290,000 Mr), and the F' allotype (210,000 Mr) was digested by restriction enzymes, and Southern blots were hybridized with CR1 cDNA and genomic probes. With the use of Bam HI and Sac I, an additional restriction fragment was observed in 20 of 21 individuals having the S allotype with no associated loss of other restriction fragments. Southern blot analysis with a noncoding genomic probe derived from the S allotype-specific Bam HI fragment showed hybridization to this fragment and to two other fragments that were also present in FF individuals. Thus, an intervening sequence may be repeated twice in the F allele and three times in the S allele. A restriction fragment length polymorphism (RFLP) unique to two individuals expressing the F' allotype was seen with Eco RV, but the absence of persons homozygous for this rare allotype prevented further comparisons with the F and S allotypes. Analysis of the CR1 transcripts associated with the three CR1 allotypes indicated that these differed by 1.3-1.5 kb and had the same rank order as the corresponding allotypes. Taken together, these findings suggest that the S allele was generated from the F allele by the acquisition of additional sequences, the coding portion of which may correspond to a long homologous repeat of approximately 1.4 kb that has been identified in CR1 cDNA. We saw two other RFLPs with Hind III and Pvu II that were in linkage dysequilibrium with the Bam HI-Sac I RFLPs associated with the S allotype, and a third polymorphism was seen with Eco RI that was not in linkage dysequilibrium with the other polymorphisms. Thus, 10 commonly occurring CR1 alleles can be defined, making this locus a useful marker for the long arm of chromosome 1 to which the CR1 gene maps. PMID- 2877047 TI - pIN32: a cointegrate plasmid with IncHI2 and IncFII components. AB - An Enterobacter cloacae strain isolated from the faeces of a child with diarrhoea in Indonesia contained a transferable 216 MDa plasmid, pIN32, exhibiting IncHI2 phenotypic characters, including temperature sensitivity of transfer and the expression of H serotype pili at a repressed level. A derivative plasmid (pIN32 1), which had lost the IncHI2 phenotype, and contained only 60 MDa of the original replicon, was obtained after mating at 37 degrees C. It was IncFII, showed regions of homology with plasmid R100, determined IncFII serotype conjugative pili constitutively and was transfer-derepressed. After overnight growth at 37 degrees C in non-selective medium, pIN32 gave rise to another derivative, pIN32-2 (size 184.3 MDa), which retained the IncHI2 phenotype and several other pIN32 characters. PMID- 2877048 TI - Mutants of Streptococcus pneumoniae that contain a temperature-sensitive autolysin. AB - Two mutants of Streptococcus pneumoniae deficient in autolysin activity produced a protein that showed immunological identity with the N-acetyl-muramyl-L-alanyl amidase present in the wild-type strain, when tested with antiserum obtained against this enzyme. The protein was produced by the mutant cultures grown either at 37 degrees C or at 30 degrees C, although only the cell extracts obtained at 30 degrees C showed significant cell wall hydrolysing activity. In contrast to the lysis resistance of these bacteria grown at 37 degrees C, mutant cultures grown at 30 degrees C exhibited significant degrees of autolysis when treated with detergent or cell wall inhibitors. Extracts of the mutant cultures contained a cell wall hydrolysing activity that was rapidly inactivated during incubation at 37 degrees C. PMID- 2877049 TI - Neuromuscular transmission in an insect visceral muscle. AB - The electrical properties of the muscles of locust oviduct have been examined using intracellular recordings. The muscle cells are both dye and electrically coupled. They possess a wide array of spontaneous electrical activity ranging from slow oscillations of membrane potential to action potentials. In addition to possessing spontaneous electrical activity, certain regions of the oviduct are under motor control. The amplitude of evoked excitatory junction potentials (EJPs) increased step wise revealing innervation from a maximum of three motor units. These EJPs underwent summation and facilitation, and reached a critical threshold at which point the membrane revealed an active response. Bath applied glutamate, aspartate, proctolin, and octopamine were tested for their ability to alter resting potential and EJPs. L-glutamate (1.6 X 10(-5) M and above) produced a dose-dependent depolarization of membrane potential accompanied by a reduction in amplitude of EJPs. Although L-aspartate resulted in similar effects, the concentrations required were higher than those for glutamate. Proctolin (6.3 X 10(-11) M-6.0 X 10(-9) M) resulted in a dose-dependent depolarization but had little or no effect on amplitude of EJPs. Application of D, L-octopamine (3.2 X 10(-5) M-1.7 X 10(-4) M) induced a small hyperpolarization and a reduction in amplitude of EJP. It is suggested that contractions of locust oviduct appear to be regulated by a combination of a classical neurotransmitter such as glutamate, along with the neuromodulators octopamine and proctolin. PMID- 2877050 TI - Advances in the surgical treatment of coronary artery disease. PMID- 2877051 TI - Advances in the pharmacologic management of angina pectoris. PMID- 2877052 TI - Low-grade lymphomas in young homosexual men without LAV/HTLV III infection. PMID- 2877053 TI - Somatostatin mRNA: regional variation in hybridization densities in individual neurons. AB - Somatostatin mRNA is detected by in situ hybridization of 35S-labeled single stranded cDNA probes to coronal sections of the rat brain that include the periventricular nucleus of the hypothalamus. Features supporting hybridization specificity include its anatomic distribution, the results of studies using multiple cDNA probes, RNAase experiments, competition studies, and correlations with patterns of somatostatin peptide immunostaining in adjacent sections. The hybridization densities vary strikingly from region to region, with highest densities in the periventricular nucleus and more modest levels in areas such as the cerebral cortex and the striatum. On the basis of the results of in situ and immunohistochemical approaches, we suggest that this variation is due to regional differences in the density of hybridization per positive cell, as well as to regional variation in the densities of somatostatinergic perikarya. PMID- 2877054 TI - Underdocumentation of benzodiazepine prescriptions in a general medicine clinic. AB - During a three-month period the authors reviewed the charts of patients prescribed benzodiazepine and non-benzodiazepine medications by 73 housestaff practicing in an ambulatory medical clinic. Compared with non-benzodiazepine prescriptions, benzodiazepine name (p less than 0.001), instructions (p less than 0.001), and targeted problems (p less than 0.0001) were significantly underrecorded. In 11% of the records reviewed there was no indication that a mood disorder had been identified or a benzodiazepine prescribed (p less than 0.0001). Problems targeted for benzodiazepine management were found less frequently in the records of elderly patients than in those of patients less than 65 years of age (p less than 0.05). The authors conclude that many houseofficers significantly underdocument the prescriptions they write for benzodiazepine medications and that this may be a marker of their regard for managing mood disorders with benzodiazepines. PMID- 2877055 TI - A consumer/medical educator conference: new objectives for the medical curriculum. AB - The authors discuss the development and proceedings of a highly structured conference at which 17 representatives from diverse non-medical groups and 14 medical educators from one medical school identified objectives needing greater emphasis in the medical curriculum. The conference emulated industry's use of consumer advisory panels. Using the nominal group technique, a group process used in business, the non-medical group developed independently a priority list of areas in which physicians might be better educated to serve society. The medical educators then joined the non-medical group to discuss and clarify the concerns given highest priority. The authors describe subsequent initiatives by the medical school to address aspects of the general concerns raised by the non medical group. The conference represents an approach to seeking input from non traditional sources in the development of the medical curriculum. PMID- 2877057 TI - Neurotransmitter administration and manipulation of growth. PMID- 2877056 TI - Responsiveness of renin secretion: a key mechanism in the maintenance of blood pressure. AB - The renin-angiotensin system is known to respond to various stimuli with a marked increase in its activity. This phenomenon is well known in relationship to changes in sodium balance. Thus, the antihypertensive effect of diuretics is often blunted or even abolished by an excessive renin response. Water deprivation and alpha-adrenoceptor blockade also elicit considerable renin responses, which as a result become a predominant factor in blood pressure maintenance. Accordingly, the renin system plays a very important role in blood pressure regulation not just because it is spontaneously activated under steady-state conditions, but even more because of its responsiveness to pharmacological and other stimuli. This may explain the surprising efficacy of angiotensin converting enzyme inhibitors, which block the generation of angiotensin II, and thereby all vascular effects of spontaneously elevated renin levels as well as of any renin response. PMID- 2877058 TI - Designer drug confusion: a focus on MDMA. PMID- 2877059 TI - Impalpable testicle. PMID- 2877060 TI - The effect of media and other variables on the BP solution rate test for slow lithium carbonate tablets. AB - The British Pharmacopoeial test for assessing the solution rate of slow lithium carbonate tablets has been evaluated using 'controlled release' tablets containing 400 mg of lithium carbonate. No significant differences in lithium release were found when the volume of media used in the test was reduced from 250 ml to 200 ml, the final stage of the test in pH 6.8 phosphate buffer reduced from 5 to 3 h, the number of tablets in each thimble reduced from three to one, or the prescribed phosphate buffers replaced with phthalate and Tris, respectively. A four-fold increased concentration of phosphate in the phosphate buffers used resulted in a significant retardation in lithium solution rate. This was not attributable to an ionic strength effect but possibly to the formation of trilithium phosphate at the interface. Dissolution studies using the USP Basket Method showed a significantly slower release rate of one tablet into 900 ml of phosphate buffer compared with Tris buffer. This difference was markedly increased when three tablets were investigated in 200 ml of similar media. These differences were considered to be due to the formation of the much less soluble trilithium phosphate in the phosphate buffers. PMID- 2877061 TI - Mechanism of dissolution of cholesterol-calcium bilirubinate compressed discs in monooctanoin. AB - The dissolution of cholesterol monohydrate and calcium bilirubinate (neutral salt) mixtures in monooctanoin was investigated using the static disc method. The intrinsic dissolution rate of calcium bilirubinate was orders of magnitude (approximately 1000 fold) lower than that of cholesterol. Cholesterol release decreased as its weight fraction in the solid decreased. In model systems containing below 50% cholesterol dissolution became negligible. The release profiles deviated from the classical model for dissolution from two component mixtures. The observed dissolution profiles of both components were greater than predicted by theory. Anomalous positive curvatures in dissolution profiles suggested that calcium bilirubinate initially reduced the surface area available for cholesterol dissolution. A model, taking into account the change in surface area, was used to fit the cholesterol dissolution data. The results were consistent with the reported relationship between human gallbladder stone cholesterol content and average stone weight loss. PMID- 2877062 TI - On the modulating effects of temperature, albumin, pH and calcium on the free fractions of phenobarbitone and phenytoin. AB - The effects of temperature, albumin, pH and Ca2+ on the binding of phenobarbitone and phenytoin to human serum albumin in buffer have been investigated using equilibrium dialysis. The free fractions of both anticonvulsants were much increased by raising the temperature. Lower free fractions were observed by increasing the albumin concentration from 5-8 g litre-1 and by raising pH from 6 to 9. No significant effect on the free fractions was observed by changing (at pH 7.4) the Ca2+ concentration from 0 to 5 mM. The observed differences in free fractions at 37 degrees C, as determined in phosphate, borate and Krebs-Ringer buffer at pH 7.4, indicate that great care is needed in the choice of dialysis fluid for dialysis of clinical samples. PMID- 2877063 TI - Effect of moderate haemodilution with fluosol-DA or normal saline on ampicillin kinetics in the rat. AB - The effects of haemodilution with either Fluosol-DA or normal saline on renal excretion and glomerular filtration have been studied in the rat. Ampicillin clearance and renal creatinine clearance were used as in-vivo measures of renal excretion and glomerular filtration, respectively. Rats were moderately exchanged with either fluid and evaluated after 0.5, 24, 48, or 72 h. After exchange, ampicillin clearance was higher, but not significantly different, and the apparent volume of distribution was increased significantly in some groups. These changes are consistent with the effects expected when plasma protein binding is reduced by haemodilution. The percent of ampicillin recovered in urine and the renal creatinine clearance were not statistically different in any group. Thus, moderate haemodilution with either fluid did not change renal function compared with unexchanged animals. PMID- 2877065 TI - Factors influencing the tissue distribution of coenzyme Q10 intravenously administered in an emulsion to rats: emulsifying agents and lipoprotein lipase activity. AB - The tissue distribution of coenzyme Q10 (CoQ10) administered intravenously in an emulsion prepared with egg yolk phosphatidylcholine (PC), egg yolk sphingomyelin (SPM) or a combination of PC and a polyoxyethylene derivative of hydrogenated castor oil (HCO-60) (PC + HCO-60) was investigated. The disappearance from the plasma of CoQ10 administered in three different emulsions of lipid particle size less than 0.5 micron varied with the particular emulsifier. Its disappearance occurred most rapidly from the PC emulsion; with the addition of HCO-60, its disappearance was much slower. In the reticuloendothelial system, the concentration of CoQ10 was higher in the spleen, for both the SPM and PC + HCO-60 emulsions than for the PC emulsion. HCO-60 reduced the CoQ10 distribution in the liver from the PC emulsion. Differences in disappearance rates from the plasma are thus considered to be due to the extent of CoQ10 distribution in the liver. CoQ10 concentration in the heart, a target organ, was greatest with the PC emulsion. Its distribution was related to lipoprotein lipase (LPL) activity in this organ. The effects caused by HCO-60, however, could not be explained by LPL activity alone. CoQ10 distribution in the adrenal gland and kidney can be explained partly by LPL activity but in the presence of HCO-60, the distribution mechanism apparently involves other factors. PMID- 2877064 TI - Pharmacological evaluation of an injectable prolonged release emulsion of physostigmine in rabbits. AB - Physostigmine was incorporated in an injectable emulsion in an attempt to prolong its pharmacological activity. Emulsions which remained stable over 6 month storage were prepared using optimal experimental conditions. The in-vitro kinetic examination revealed that the rate-determining step in the release process of physostigmine from the emulsion was its partitioning from the oily phase to the external aqueous phase. The in-vivo results indicated that the physostigmine emulsion was able to inhibit the cholinesterase activity for only 1 to 2 h. The preliminary pharmacokinetic analysis showed that the physostigmine emulsion apparently increased the bioavailability compared with the conventional injectable solution. This could be attributed either to the protection of the sensitive drug from the enzymatic degradation or to improved absorption. The presence of poloxamer micelles in the aqueous phase was shown to enhance the bioavailability of physostigmine without having any effect on its pharmacological activity or duration. PMID- 2877066 TI - Characterization of mitomycin C-induced gastrointestinal damage: changes in the gastric absorption of drugs in rats. AB - The effect of mitomycin C (MMC) pre-administration intravenously on the absorption of drugs from rat stomach has been examined by means of the in-situ loop technique. 48 h after the MMC-treatment, the absorption of salicylic acid, aspirin and sulphanilic acid was not influenced but that of sulphanilamide was significantly increased compared with the control. At 96 h, a differential effect of MMC on the absorption of each drug was seen: the absorption of weakly acidic drugs was significantly decreased while that of bases and strong sulphonic acid increased. The decreased absorption of salicylic acid and aspirin correlated with the reduced gastric mucosal blood flow. At 96 h there were severe haemorrhagic lesions in the gastric mucosae. The increase in absorption of poorly absorbed drugs could be ascribed to the increased permeability of the blood-gastric epithelium barrier as was evidenced by leakage of Evans Blue. PMID- 2877067 TI - [3H]noradrenaline-releasing action of vinpocetine in the isolated main pulmonary artery of the rabbit. AB - Vinpocetine (10(-6)-3 X 10(-5) M) increased both the resting and the nerve stimulation-evoked release of [3H]noradrenaline from the isolated main pulmonary artery of the rabbit in the presence of uptake blockers (cocaine, 3 X 10(-5) M; corticosterone, 5 X 10(-5) M), and inhibited the nerve stimulation-evoked postsynaptic response. The resting transmitter releasing action of vinpocetine increased in the absence of cocaine. Exogenously applied (-)noradrenaline [(-)NA] (10(-6) M) or clonidine (10(-6) M) inhibited the vinpocetine (3 X 10(-5) M) potentiated [3H]NA release and contracted the circular muscle. The clonidine induced contraction was abolished by 10(-7) M prazosin. The inhibitory action of (-)-NA on vinpocetine-potentiated [3H]NA release was partly antagonized by 3 X 10(-7) M yohimbine, a preferential alpha 2-adrenoceptor blocker. In Ca-free Krebs solution containing 1 mM EGTA the neurotransmitter releasing action of vinpocetine was abolished, however, its stimulating action on the resting [3H]NA outflow was not changed. In Na-pump-inhibited arteries (K-free solution), where both the resting and the nerve stimulation-evoked release of neurotransmitter had already been increased, vinpocetine further enhanced the nerve stimulation-evoked release of [3H]NA. It is concluded that vinpocetine may have alpha 2- and alpha 1 adrenoceptor blocking action, as well as a tyramine-like effect. The presynaptic neurotransmitter releasing action of vinpocetine is presumably the consequence of its inhibitory action on the Ca-pump which is suggested by the finding that in K free solution vinpocetine was able to enhance further the release of neurotransmitter. PMID- 2877068 TI - The activity of non-steroidal anti-inflammatory drugs in the rat mesenteric vasculature. AB - Rat isolated, perfused mesenteric blood vessels have been used to determine whether non-steroidal anti-inflammatory drugs (NSAIDs) display selectivity for inhibition of vasoconstrictor responses to noradrenaline compared with those to calcium. The rank order of potency of the NSAIDs for inhibition of responses to noradrenaline was: meclofenamate greater than flufenamate = diclofenac greater than indomethacin greater than fenbufen greater than phenylbutazone greater than ibuprofen greater than ketoprofen greater than naproxen greater than paracetamol (included as an inhibitor of cyclo-oxygenase). All NSAIDs show selectivity for noradrenaline (mean selectivity molar ratio = 0.19; s.e.m. 0.15-0.23) but there was a positive correlation (r = 0.98, P less than 0.001) between inhibition of responses to noradrenaline and those to calcium. The depressant effect of meclofenamate and of fenbufen, the most potent and most selective in the series, respectively, on responses to noradrenaline, was completely reversed to control values by prostaglandin E2. The results support previous findings that inhibition of cyclo-oxygenase in rat mesenteric blood vessels leads to a loss of response to noradrenaline. Comparison of the present data for inhibition of responses to noradrenaline in the mesentery with published data indicates that the mesentery bears a greater similarity to other in-vitro rather than in-vivo models for screening NSAIDs. PMID- 2877069 TI - Polysorbate 20 as a drug release regulator in ethyl cellulose film coatings. AB - Tablet coatings of hydrophobic ethyl cellulose have been made more hydrophilic by the addition of a non-ionic surfactant, polysorbate (Tween) 20, to the film. As its content increased, so did the release of sodium salicylate from the coated tablets. With a certain content of surfactant and specific thickness of the tablet coat, zero order release kinetics were observed. Leaching of the polysorbate 20 occurred from all formulations. Scanning and transmission electron micrographs showed that the structure of the coats consisted of several layers parallel to the tablet surface. Polysorbate 20 was seen as small drops in some coats. PMID- 2877070 TI - Effect of urapidil on rat brain catecholamine synthesis. AB - The effects of urapidil, a clinically effective antihypertensive drug, on the in vivo rate of synthesis of rat brain noradrenaline (NA) and dopamine (DA) was determined. A significant dose-dependent increase in dopa concentration by urapidil after dopa decarboxylase inhibition by NSD 1015 was observed in brain stem (3-30 mg kg-1 i.p.) and striatum (10-30 mg kg-1 i.p.), indicating increased NA and DA turnover, respectively, most probably a result of central blockade of brainstem alpha 1-adrenergic and striatal DA receptors. These results indicate that urapidil may possibly exert its central hypotensive action in part by a reduced influence on brain stem NA, thus reducing central sympathetic outflow. PMID- 2877071 TI - Dopaminergic metabolism in various rat brain areas after L-dopa loading. AB - The time course of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT) and 3-methoxytyrosine (3-O Medopa) concentrations in rat brain after treatment with L-dopa + benserazide has been investigated in the striatum, hypothalamus, hippocampus and cerebellum. These areas were selected for their different dopaminergic activities. After L dopa loading, DA, DOPAC and HVA were increased in all the structures, but the largest increases were in those tissues with the less dopaminergic activity, while 3-MT increased in the hypothalamus, hippocampus and cerebellum but was lowered in striatum. 3-O-Medopa, which is the direct product of the O-methylation of L-dopa, did not show any specific distribution. The data provide evidence that the striatum, by feed-back mechanisms and specific enzymatic activity, is able to ensure a better regulation of dopaminergic activity than the other structures, thereby overcoming excess L-dopa. PMID- 2877072 TI - Enhanced myocardial necrosis induced in rats by the combined administration of hydralazine and prenalterol. AB - The cardiotoxic effects of hydralazine and prenalterol, given alone and in combination, were assessed in rats and rabbits. Acute myocardial necrosis was induced by a single administration of each drug alone in rats. However, the incidence and severity of lesions were markedly enhanced when both drugs were given in combination. Rats that received the same treatment for 10 consecutive days showed minimal or no acute necrosis, demonstrating the development of a resistance to further cardiotoxic effects of the drugs. Rabbits showed only minimal lesions when either drug was used alone and no enhancement of lesions when they were given in combination. From these data, it is concluded that the possibility of a cardiotoxic interaction exists when these drugs are used in combination and that the heavy rat (500-600 g) is a more sensitive model than the rabbit for studies of this nature. PMID- 2877073 TI - Optimizing the pentetrazol infusion test for seizure threshold measurement. AB - Seizure thresholds in mice were determined using the pentetrazol infusion method. Concentration of infusate and rate of infusion were varied to assess the optimal parameters for seizure threshold detection. Seizure threshold elevations were produced by flurazepam and threshold decreases by FG 7142. An infusion rate of 1.1 ml min-1 was best for detecting both increases and decreases in threshold. However a concentration of 2.5 mg ml-1 gave optimal measurement of elevations in threshold whereas decreased thresholds were best detected with a concentration of 10 mg ml-1. PMID- 2877074 TI - Chronic subcutaneous treatment with acebutolol: haemodynamic effects and metabolism in spontaneously hypertensive rats. AB - Chronic administration of acebutolol (15 mg kg-1 s.c. three times a week for five weeks, then 30 mg kg-1 for three weeks) did not lower blood pressure in 17 and 33 weeks-old spontaneously hypertensive rats (SHR). At the end of this treatment, the plasma concentrations of acebutolol and diacetolol were measured by HPLC. After 24 h, acebutolol was absent from plasma while diacetolol was lower after chronic treatment than after acute administration. Twenty-four hours after the last injection of acebutolol, both isoprenaline-induced tachycardia and vasodilatation were reduced. The vasomotor agents, noradrenaline, bradykinin and angiotensin, exhibited the same activity in control and treated SHR. These findings suggest that the lack of antihypertensive effect of acebutolol in SHR may be the result of a decrease in diacetolol formation together with blockade of beta 2 vascular receptors. PMID- 2877075 TI - Does naloxone induce relaxation of guinea-pig airway smooth muscle? AB - The effects of the opiate receptor antagonist naloxone were investigated on isolated preparations of guinea-pig trachealis contracted with either histamine, methacholine or KCl. The commercially available solution of naloxone (Narcan) induced concentration-dependent relaxation of the contracted airway preparations. In stark contrast, aqueous solutions of naloxone were without any significant relaxant effect. Aqueous solutions of the preservatives (methyl and propyl hydroxybenzoate) present in the vehicle used in the commercial formulation of naloxone mimicked exactly the relaxant effects induced by Narcan. Thus, naloxone does not directly induce relaxation of airway smooth muscle. The effects of Narcan can be solely attributed to the activity of the preservatives present in the vehicles. The mechanism underlying the bronchodilator activity of methyl and propyl hydroxybenzoate is unknown but is not related to receptor blockade or to alterations in the intracellular levels of cyclic AMP. PMID- 2877076 TI - ICI 180080, a novel selective thromboxane receptor antagonist: synthesis and relative activity. AB - The preparation of a novel potent thromboxane receptor antagonist ICI 180080, 5(Z)-7-[2,2-dimethyl-4-(2-hydroxyphenyl)-1,3-dioxan-cis-5-yl] heptenoic acid, is described together with its methyl ether and methyl ester. Thromboxane antagonist pA2 data against U 46619 is presented for rabbit thoracic aorta in-vitro (ICI 180080, pA2 = 7.5). The relative antagonist pA2 values obtained are discussed in terms of the chemical structure of the molecules. The potent activity of ICI 180080 is attributed to a specific orientation of the phenolic oxygen, due to an intramolecular hydrogen bond. PMID- 2877077 TI - Compounds extracted from feverfew that have anti-secretory activity contain an alpha-methylene butyrolactone unit. AB - Extracts of feverfew inhibit secretion of granular contents from platelets and neutrophils and this may be relevant to the therapeutic value of feverfew in migraine and other conditions. In this investigation we fractionated an extract of feverfew and obtained eleven fractions with antisecretory activity. The activity. The active fractions, together with two fractions that were devoid of anti-secretory activity, were examined using 1H NMR and infrared spectroscopy. All the active fractions (but neither of the inactive fractions) contained compounds with an alpha-methylene butyrolactone unit. Five compounds that contain this unit were identified as parthenolide, 3-beta-hydroxyparthenolide, secotanapartholide A, canin and artecanin, all of which are sesquiterpene lactones. It is very likely that these and other sesquiterpene lactones that contain an alpha-methylene butyrolactone unit are responsible for the anti secretory activity in extracts of feverfew. PMID- 2877079 TI - Measurement of concentrations of the histamine H1 receptor antagonist temelastine in biological fluids. AB - A high-performance liquid chromatographic analysis of temelastine in biological fluids with UV detection at 229 nm is presented. The method involves ether extraction followed by re-extraction into phosphoric acid and chromatography on a reversed-phase column. The method has a lower limit of detection of 0.05 mg L-1 and is adequate for use in pharmacokinetic studies following oral administration. PMID- 2877078 TI - [Studies on Ganoderma lucidum. VI. Anti-allergic effect. (1)]. PMID- 2877080 TI - Tournament badminton. Podiatric perspective. PMID- 2877081 TI - Actions of nizatidine, a selective histamine H2-receptor antagonist, on gastric acid secretion in dogs, rats and frogs. AB - Nizatidine (LY139037), a selective histamine H2-receptor antagonist, is a potent inhibitor of gastric acid secretion. It was 17.8 times as active as cimetidine on histamine (10(-5) M)-induced secretion from the isolated gastric mucosa of the bullfrog. Nizatidine was 8.9 times as active as cimetidine on basal acid secretion of the chronic gastric fistula rats after s.c. administration. Against acid secretion from the vagally innervated gastric fistula and Heidenhain pouch of dogs stimulated with submaximal doses of histamine, methacholine and gastrin, nizatidine was, respectively, 6.5, 5 and 4.7 times as active as cimetidine by i.v. administration. Nizatidine was very well absorbed from the gut and was 5 to 10 times as active as cimetidine on gastric acid secretion of dogs induced by submaximal and maximal doses of histamine when given p.o. Equal molar doses of nizatidine showed equal peak effects when given i.v., s.c. or i.m. Pharmacological data indicate that nizatidine is safe and effective as an agent for the control of excessive gastric acid secretion. PMID- 2877082 TI - Beta adrenoceptor modulation of the generation of murine cytotoxic T lymphocytes in vitro. AB - The effects of stimulating beta adrenoceptors on lymphocytes during the generation of cell-mediated immunity were examined. In an in vitro system for the generation of murine cell-mediated cytotoxicity, addition of isoproterenol (10( 7) M), epinephrine (10(-6) M) or norepinephrine (10(-4) M) enhanced the number of lytic units generated compared to control cultures. This increase was blocked by dl-propranolol (5 X 10(-6) M). I-Propranolol (10(-11) to 10(-7) M) blocked the isoproterenol-induced increase in lytic units per culture, but d-propranolol (10( 11) to 10(-7) M) did not. Terbutaline (10(-5) M), a relatively selective beta-2 agonist, similarly augmented the generation of cell-mediated cytotoxicity, with the increase again blocked by propranolol. Butoxamine (5 X 10(-6) M), a beta-2 antagonist, but not atenolol (5 X 10(-6) M), a beta-1 antagonist, blocked the epinephrine-induced increase in cell-mediated cytotoxicity. Addition of phentolamine (5 X 10(-6) M) had no effect on the epinephrine-induced increase in lytic units per culture. However, in the presence of phentolamine, norepinephrine increased lytic units per culture to a greater degree than that seen with norepinephrine alone, suggesting a balance between positive beta effects and inhibitory alpha effects upon simultaneous alpha and beta stimulation. These data provide further evidence for an immunoenhancing role of beta receptor stimulation during the generation of immune responses. PMID- 2877083 TI - Interactions of atrial natriuretic peptide with the sympathetic and endocrine systems in the pithed rat. AB - We have found previously that atrial natriuretic peptides (ANPs) attenuate pressor response to alpha-2 adrenoceptor agonists but not to alpha-1 agonists in the pithed rat. We have now investigated the effects of ANP on other pressor agonists and on sympathetically mediated responses in rats. Bolus-injected ANP (0.1-10.0 nmol/kg) attenuated pressor responses to angiotensin II, vasopressin and alpha-2 adrenoceptor-mediated component of norepinephrine (NE)-induced responses (up to 17, 27 and 15%, respectively) in pithed rats. The threshold antipressor dose of ANP was the lowest for angiotensin II (comparable to normal levels of circulating ANP-immunoreactivity in rats) whereas it was higher for vasopressin and NE (comparable to plasma ANP-immunoreactivity stimulated by volume expansion). A 30-min infusion of ANP (0.15 nmol/kg/min) shifted the NE dose-pressor response curve 1.7-fold to the right. Conversely, neither that rate of ANP infusion nor the highest dose of bolus injected ANP altered pressor and plasma NE responses to sympathetic stimulation in demedullated pithed rats. However, at higher infusion rates, ANP reduced sympathetic stimulation-induced pressor responses (2.6-fold) and elevations of plasma NE levels (1.6-fold), without altering NE clearance. Similarly in conscious rats, ANP infusion prevented a reflex increase in plasma NE concentrations associated with hypotension. Thus, although the intrajunctional alpha-1 and presynaptic alpha-2 adrenoceptors are inaccessible to the short term bolus-induced elevation of circulating ANP during longer term increases in plasma ANP, it does reach the junction, reduces NE release and limits effects of receptor activation, possibly by diminishing Ca++ entry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877084 TI - Alpha-1 adrenoceptor antagonist effects of the optical isomers of YM-12617 in rabbit lower urinary tract and prostate. AB - The alpha-1 adrenoceptor antagonist effects of the optical isomers of YM-12617 (5 [2-[[2-(o-ethoxyphenoxy)ethyl]amino]propyl]- 2-methoxybenzenesulfonamide HCl), a potent and selective alpha-1 adrenoceptor antagonist, were evaluated in the rabbit lower urinary tract and prostate. R-(-)-YM-12617 (1 X 10(-10) to 3 X 10( 9) M) and S-(+)-YM-12617 (3 X 10(-8) to 3 X 10(-7) M) antagonized phenylephrine induced contraction in a competitive manner in the urinary bladder base (trigone), proximal urethra and prostate. The mean pA2 value for R-(-)-YM-12617 at the alpha-1 adrenoceptor of trigone, urethra and prostate was 9.91, 9.62 and 9.92, respectively, and that for S-(+)-YM-12617 was 8.09, 7.92 and 7.77, respectively. Therefore, R-(-)-YM-12617 is a 50 to 141 times more potent antagonist than S-(+)-YM-12617 at the alpha-1 adrenoceptor in these tissues. The present results also indicate that the alpha-1 adrenoceptor in the lower urinary tract and prostate can distinguish clearly between the optical isomers of YM 12617. Similar results were obtained in the aorta of rabbits in which a dramatic stereochemical preference of R-(-)-YM-12617 for the alpha-1 adrenoceptor also exists. PMID- 2877086 TI - Intrinsic gamma aminobutyric acid receptors modulate the release of catecholamine from canine adrenal gland in situ. AB - Immunohistochemical analysis documented the presence of gamma-aminobutyric acid (GABA)-containing fibers and GABA-containing chromaffin cells in canine adrenal glands. A dense network of fibers was visualized at the boundary between medullary and cortical cells, and, in the medullary tissue, GABA-containing fibers surrounded chromaffin cells. Some of these fibers enter the adrenal medulla together with splanchnic cholinergic nerves. The functional role of the GABAergic system in the regulation of catecholamine release from adrenal chromaffin cells was studied in canine adrenal glands in situ, using an autoperfusion system for the adrenal gland that was designed to eliminate indirect central effects of drugs or their metabolites on catecholamine release. The present study documents that GABA modulates the spontaneous release of catecholamines and the release elicited by electrical stimulation of the splanchnic nerve. GABAA receptor agonists such as THIP or muscimol increased the catecholamine content in adrenal effluent blood, whereas bicuculline (0.05 mmol/2 ml min-1), a GABAA receptor antagonist, reduced it. Baclofen (0.094 mmol/2 ml min 1), a GABAB receptor agonist, failed to alter the catecholamine content in adrenal effluent blood. The increased release of catecholamines elicited by 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3[2H]-one (THIP; 0.143 mmol/2 ml min-1) was prevented by bicuculline (0.05 mmol/2 ml min-1) but not by hexamethonium (2.48 mmol/2 ml min-1) or naloxone (0.122 mmol/2 ml min-1). Furthermore, denervation of the adrenal glands failed to prevent the THIP-elicited release of catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877085 TI - Release of acetylcholine mediated by cholecystokinin receptor from the guinea pig sphincter of Oddi. AB - Mechanisms involved in the action of cholecystokinin octapeptide (CCK-8) on the isolated circular muscle of the guinea pig sphincter of Oddi were investigated. CCK-8 (10(-9) to 10(-6) M) caused a concentration-dependent contraction of the sphincter. Angiotensin II, bethanechol and serotonin also contracted this tissue. CCK-8 exerted the most potent effect. However, bradykinin, porcine motilin and norepinephrine failed to elicit any contraction. The CCK-8-induced contraction was inhibited by about 60% by atropine (3 X 10(-7) M) or tetrodotoxin (3 X 10(-7) M) but was not affected by hexamethonium (3 X 10(-5) to 10(-4) M) or phentolamine (3 X 10(-6) to 10(-5) M). Proglumide (3 X 10(-4) to 3 X 10(-3) M), a derivative of glutaramic acid, inhibited competitively the contraction by CCK-8. However, proglumide influenced neither the electrically elicited twitch contraction nor the bethanechol-induced contraction. CCK-8 evoked a concentration-related release of [3H]acetylcholine (ACh) from previously labeled stores. The CCK-8-evoked release of [3H]ACh was eliminated by tetrodotoxin and was inhibited, in a concentration-dependent manner, by proglumide. These results suggest that the contractile response to CCK-8 of the guinea pig sphincter of Oddi consists of a direct effect on the smooth muscle and an indirect effect mediated by ACh release from postganglionic parasympathetic neurons. PMID- 2877087 TI - In vitro effects of beta adrenoceptor agonists and antagonists on the rat ovarian suspensory ligament. AB - The mesovarian suspensory ligament of the rat was used to compare the activities of beta adrenoceptor agonists and antagonists. The following beta adrenoceptor agonists, in descending order of potency, inhibited spontaneous activity in a dose-related manner: zinterol greater than isoproterenol much greater than dobutamine. Several noncardioselective, beta-2 adrenoceptor antagonists with intrinsic sympathomimetic activity (ISA) also inhibited the activity of the ligament: pindolol greater than alprenolol = bucindolol = oxprenolol greater than labetalol. Maximal relaxation induced by the antagonists was equivalent to that caused by the beta receptor agonists. Two cardioselective, beta adrenoceptor antagonists with ISA, acebutolol and practolol, did not inhibit the activity of the suspensory ligament but did increase the rate of the isolated right atrium of the rat. The maximal increases in atrial rate evoked by the antagonists were significantly less than those induced by the beta adrenoceptor agonists. Studies with ICI 118,551 or atenolol as beta-2 or beta-1 selective adrenoceptor blockers, respectively, suggest that the beta adrenoceptors of the suspensory ligament are predominantly of the beta-2 subtype. The possible relevance of these results to the induction of mesovarian leiomyomas in rats by noncardioselective beta adrenoceptor agonists and antagonists with ISA is discussed. PMID- 2877088 TI - [The neurohormones]. PMID- 2877089 TI - [Neurochemical aspects of interneuronal communication]. AB - It is suggested that the term neurotransmission, which is used to designate neuronal communication at synaptic level, be associated to the less restrictive term neuromodulation. These two types of intercellular communication seem in fact to be two basically different mechanisms, both of which contribute to neuronal integration. The integration of neuronal information at cellular level appears to be more complex than the simple addition of excitatory plus inhibitory influences eliciting postsynaptic responses. Evidence has been obtained that non synaptic transmission can alter the capacity of a given synapse to transfer neuronal information from the presynaptic element to the postsynaptic neuron. For instance, presynaptic mechanisms provide evidence for the functional independence of the nerve terminals, since the release of neuromediators by the latter is sometimes independent of the axonal firing rate. Similarly, the somato-dendritic part of some neurons exhibits intrinsic functions, such as a dendritic release of neuromediator, suggesting that the control of the axonal firing rate takes place partly at this somato-dendritic level and does not depend for the totality on afferent axonic information. The intercellular operations which organize individual neurons into neuronal networks will also occur either at somato dendritic level or at the level of specific nerve terminals selected as the result of presynaptic interactions. This integration of neuronal information also seems to take place at postsynaptic level, where cooperative interactions have been shown to occur between various receptors. These mechanisms will function at the level of a single nerve terminal containing more than one neuromediator. Neuromodulation can therefore be said to involve very efficient adaptive processes, which help to account for the fact that such large behavioral responses are expressed by such a small number of neuronal elements. PMID- 2877090 TI - Ceramic/metal solder connectors. PMID- 2877091 TI - Pain control in advanced cancer: pharmacological methods. PMID- 2877092 TI - [Perirenal hematoma diagnostic of periarteritis nodosa. Apropos of a case]. AB - Hematoma of the renal space may be of various causes. Polyarteritis nodosa can be revealed by a perirenal hematoma as in the case reported but this is a rare complication of the disease. A case of a young man with a previous history of hepatitis Hbs+ is reported. PMID- 2877093 TI - The integrated use of Toxorhynchites amboinensis and ground-level ULV insecticide application to suppress Aedes aegypti (Diptera: Culicidae). PMID- 2877094 TI - Classification of the subgenus Toxorhynchites (Diptera: Culicidae). II. Revision of the Toxorhynchites acaudatus group. PMID- 2877095 TI - Partial characterization of chicken Thy-1 glycoprotein by monoclonal antibodies. AB - A panel of monoclonal antibodies has been raised to Thy-1 purified from chicken brain. They were produced by immunization of Balb/c mice with a Thy-1-enriched (Sephacryl B) fraction of a lentil lectin-positive fraction from solubilized brain membrane proteins. Antibody-secreting clones were found to be specific for Thy-1 by enzyme-linked immunosorbent assay (ELISA) and Western transfer and immunoblotting. Four of the monoclonal antibodies were of the IgG2b isotype, one was IgG1, and one was IgM. In additivity and competition ELISA, it was found that three of the antibodies bound to the same (or similar) epitopes, and three had different epitope specificities. These monoclonal antibodies have been used to examine the development and distribution of Thy-1 in the central nervous system of chicken. PMID- 2877096 TI - Heterogeneity of sodium-dependent excitatory amino acid uptake mechanisms in rat brain. AB - The pharmacologic and kinetic characteristics of sodium-dependent uptake of [3H]L glutamate, [3H]D-aspartate, and [3H]L-aspartate into crude synaptosomal preparations of rat corpus striatum and cerebellum have been examined in vitro. In cerebellum the apparent Kts and Vmax for the three excitatory amino acids were identical whereas in striatal synaptosomes, the Vmax for [3H]L-glutamate was 30% greater (P less than or equal to .001) than for [3H]D-aspartate and 50% greater (P less than or equal to .001) than for [3H]L-aspartate. L-Amino adipic acid inhibited the uptake of the three amino acids in both regions of brain was 15- to 20-fold more potent in cerebellum than in striatum. In contrast, dihydrokainic acid inhibited transport processes in the corpus striatum but was without activity in cerebellar preparations. The neurotoxin kainic acid blocked only a portion (60%) of [3H]L-glutamate and [3H]D-aspartate uptake in cerebellum while completely inhibiting amino acid transport in corpus striatum. Three days post kainic acid lesion, [3H]D-aspartate uptake was attenuated more than [3H]L glutamate uptake in the corpus striatum; destruction of corticostriatal afferents reduced [3H]L-glutamate to a greater extent than [3H]D-aspartate. Various lesions of the cerebellum affected excitatory amino acid transport processes to a similar extent. These results suggest that excitatory amino acid transport systems are pharmacologically distinct in different brain regions and may be heterogeneous within a single region. PMID- 2877098 TI - Systemic necrotizing vasculitis presenting as epididymitis. AB - Epididymitis is an uncommonly recognized complication of systemic necrotizing vasculitis. We report 2 cases in which epididymitis heralded the onset of more severe visceral organ involvement. Early biopsy of atypical epididymitis in patients with hypertension or constitutional symptoms is important if effective therapy is to be instituted before irreversible organ damage occurs. PMID- 2877097 TI - Putative glutamate receptors in membranes obtained from heads of Drosophila melanogaster. AB - The specific binding of L-[3H]-glutamic acid (GLU) was examined in membrane preparations derived from heads of Drosophila melanogaster. L-[3H]-GLU bound to the membrane preparation with biphasic kinetics in a reversible and saturable way. The specific binding was inhibited by Cl- and Ca2+ ions. Saturation analysis of the data fit a model of two independent binding sites with dissociation constants (KD) of 29 nM and 249 nM and corresponding binding site densities (Bmax) of 5.7 and 24.6 pmol/mg protein. A series of excitatory amino acid receptor agonists and antagonists were tested as inhibitors of L-[3H]-GLU specific binding. Some compounds almost totally abolished the specific binding, whereas others reduced the binding to 45% over the concentration range used. Among the first type of inhibitors, L-GLU was the most potent, D-aspartate (D ASP) and D-GLU were 10 times less effective than L-GLU, whereas quisqualic acid had the lowest potency. Among the second type of inhibitors, glutamate diethyl ester, D-alpha-amino adipate, and N-methyl-D-aspartate showed the highest potency, and DL-2-amino-4-phosphonobutyrate was the less effective. Kainic acid and gamma-amino butyric acid were not able to modify at any concentration used the specific binding of L-[3H]-GLU. These data suggest the presence of putative GLU receptors in the brain of Drosophila. PMID- 2877099 TI - Acute biochemical and functional alterations in the partially obstructed rabbit urinary bladder. AB - Rapid structural and functional alterations have been noted in several models of partial outlet obstruction. To better characterize the rapid progression of alterations, the partially obstructed urinary bladders of mature NZW male rabbits were studied at 1, 3, 5, 7 and 14 days of outlet obstruction with respect to muscarinic receptor density, DNA, RNA, lipid and hydroxyproline content. Functional characteristics were assessed by measuring the in vitro response of the whole bladder to cholinergic and field stimulation. Wet weight increased eight-fold by day 7, decreasing to four-fold at day 14. Receptor density decreased by 50% by day 1 and remained low throughout. Although DNA concentration varied only slightly from controls, RNA increased four-fold by day 7. Hydroxyproline concentration per mg. tissue decreased in the obstructed bladder, yet total hydroxyproline content of the obstructed bladder significantly increased. Total lipids increased significantly during day 3 through 7 and decreased by day 14. Cystometry revealed a large capacity low pressure system at day 1 which rapidly changed to a low compliance system of lesser volume by day 14. Bladder emptying was significantly impaired in all obstructed specimens. Additionally, electrical field stimulation was significantly less effective than cholinergic stimulation in effecting bladder emptying. The above findings suggest that rapid changes in biochemical parameters occur during the early stage of acute obstruction which may in part be secondary to metabolic or inflammatory alterations in the detrusor. It additionally suggests that the myogenic alterations in partial outlet obstruction are rapid and partially adaptive, while neurogenic alterations appear degenerative and display a lesser degree of short term adaptation. PMID- 2877100 TI - Antibodies to HTLV-I in Japanese immigrants in Brazil. PMID- 2877101 TI - Reducing long-term diazepam prescribing in office practice. A controlled trial of educational visits. AB - We conducted a controlled, statewide trial of the efficacy of an educational visit by a physician counselor in the reduction of diazepam prescribing in outpatient practice. A novel aspect of this trial was the provision of a schedule for gradual withdrawal of long-term diazepam users from drug therapy; 51% of visited doctors attempted to withdraw patients from diazepam therapy and 26% utilized the withdrawal schedule. The entire group of 43 visited doctors reduced the rate of long-term diazepam users in their practice by 18% relative to the control group; the subgroup of doctors who utilized the withdrawal schedule had and even greater reduction of 33%. These results suggest that practicing doctors are concerned with long-term use of diazepam and that the educational visit by another physician is one method for reducing such use. PMID- 2877102 TI - Clinical laboratory manifestations of exposure to dioxin in children. A six-year study of the effects of an environmental disaster near Seveso, Italy. AB - Following a major environmental accident near Seveso, Italy, on July 10, 1976, we attempted to determine if the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) released into the atmosphere had any effect on the liver function and lipid metabolism of exposed children. From July 1976 to June 1982, we analyzed the results of more than 4500 laboratory tests (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, cholesterol, and triglycerides in plasma and delta-aminolevulinic acid in urine) in a population of about 1500 children aged 6 to 10 years at the moment of the accident. The children exposed to the highest concentration of TCDD showed alterations in serum gamma glutamyltransferase and alanine aminotransferase activity compared with the control group. These differences were restricted to values inside limits set from the lower end of the normal range to slightly above it. The observed abnormalities were slight and disappeared with time. PMID- 2877103 TI - Cardiovascular effects of ICI 118,587, a new beta-adrenoceptor partial agonist in man. AB - Effects of a new selective beta1 partial agonist, ICI 118,587, on cardiac function were assessed in clinical settings. In 7 patients, responses to multistage treadmill exercise were studied before and after an acute intravenous injection of the drug. The heart rate and blood pressure were not altered by ICI 118,587 at rest but increases in both parameters in response to exercise were significantly reduced. Neither oxygen consumption nor plasma norepinephrine level was modified by the drug both at rest and during exercise. The long term effects of ICI 118,587 were assessed in 6 patients with mild to moderate cardiac failure consequent upon ischemic heart disease. After chronic administration of the drug exercise duration was increased. The symptom-limited maximal oxygen consumption increased by 16%, associated with prolongation of the exercise tolerance. In those patients who also had symptoms of angina pectoris, exercise levels which caused angina during the control study were tolerated without symptoms after ICI 118,587. Twelve patients with nocturnal bradycardia resulting from atrial fibrillation of sick sinus syndrome were treated with ICI 118,587. Monitoring of heart rate by 24-hour Holter ECG showed that ICI 118,587 increased minimal heart rate during sleep. Being a beta1-adrenoceptor partial agonist, it has both agonist and antagonist properties. Thus, ICI 118,587 buffers the heart from an excessively low sympathetic tone which may occur during sleep and from an excessively high tone during exercise. It appears to be of benefit in the treatment of mild to moderate cardiac failure consequent upon ischemic heart disease. It also improves oxygen demand-supply imbalance without inducing further myocardial depression or inappropriate bradycardia at rest. ICI 118,587 may therefore be described as a cardiostabilizer. PMID- 2877104 TI - [Effects of opiate and opioid peptides administered intrathecally on the pain threshold and micturition reflex in rats]. PMID- 2877105 TI - [V-V bypass ECLA (extracorporeal lung assist) with a double lumen catheter for neonates]. PMID- 2877106 TI - [Clinical trial of bestrabucil (KM 2210) in hematopoietic malignancies]. AB - Thirteen patients with hematological neoplasms were treated with Bestrabucil (100 mg/day po, total dose 700-9,900 mg), which is the benzoate of an estradiol chlorambucil conjugate. The diseases from which they suffered consisted of T-cell leukemia (3), lymphoma (3), myeloma (5) and essential thrombocytosis (2). Although this drug was less effective against myeloma, the other diseases were more or less relieved with this medication. That is, Bestrabucil was effective in all three patients with T-cell leukemia, both with essential thrombocytosis and two of the three with lymphoma. It is most interesting that adult T-cell leukemia (ATL) cells decreased remarkably with Bestrabucil, along with the disappearance of several symptoms (bone pain, hypercalcemia etc.). The main side effects during this medication were mammary pain (eight of 13 patients, 62%), anorexia (five of 13 patients, 39%) and loss of libido (three of 13 patients, 23%), but neither severe myelosuppression nor hepatorenal dysfunction was induced. PMID- 2877107 TI - [Liver function tests: analysis of biliary tract enzymes and serum secretory enzymes--ALP, gamma-GTP, LAP, and ChE]. PMID- 2877108 TI - [Liver function tests: analysis of serum isoenzymes--GOT, LDH, ALP, gamma-GTP and ChE]. PMID- 2877109 TI - Adrenoceptor blocking and cardiovascular effects of the optical isomers of amosulalol (YM-09538), a combined alpha- and beta-adrenoceptor blocking agent, and the corresponding desoxy derivative (YM-11133) in rats. AB - The pharmacological activities of the enantiomers of amosulalol (YM-09538), a combined alpha- and beta-adrenoceptor antagonist, and the corresponding desoxy derivative (YM-11133) were investigated in the cardiovascular system of rats. The optical isomers of amosulalol and YM-11133 antagonized the vasopressor effect of phenylephrine and the positive chronotropic effect of isoproterenol in normotensive pithed rats. Based on DR2 values (micrograms/kg, i.v.) obtained from Schild plots, (+)-amosulalol and YM-11133 (DR2 = 30) were approximately 10 times more potent than (-)-amosulalol (DR2 = 324) in blocking alpha 1-adrenoceptors. For beta 1-adrenoceptors, in contrast, (-)-amosulalol (DR2 = 107) was approximately 60 times more potent than (+)-amosulalol (DR2 = 6460), which was almost equipotent with YM-11133 (DR2 = 3250). The results indicate that the optical isomers of amosulalol interact differently with alpha 1- and beta 1 adrenoceptors. The effects of these phenethylamines on blood pressure and heart rate were studied in urethane-anesthetized rats (i.v.). The rank order of hypotensive potency in anesthetized rats [+)- = desoxy greater than (-)-form) was consistent with the rank order of alpha 1-adrenoceptor antagonism in pithed rats. In contrast, (-)-amosulalol having a more potent beta 1-adrenoceptor antagonist activity than (+)-amosulalol and YM-11133 only produced dose-dependent bradycardia at the hypotensive doses. The results indicate that the vascular alpha 1- and cardiac beta 1-adrenoceptor blocking activities of the optical isomers of amosulalol contribute to their hypotensive and bradycardia, respectively. Thus, the racemate of amosulalol appears to exert an overall activity reflecting the activities of the individual isomers. PMID- 2877110 TI - Nigral-induced decrease in striatal blood flow and the influence on this decrease of several drugs in reserpinized and non-reserpinized cats. AB - The effect of nigral electrical stimulation on regional blood flow in the caudate nucleus and the cerebral cortex, and the influence of several drugs on these effects were examined in reserpinized or non-reserpinized cats. A double thermistor element was inserted into the left caudate nucleus, and a plate-type thermocouple element was put on the left cerebral cortex. The left substantia nigra was electrically stimulated for 10 sec through a concentric bipolar electrode with a diameter of 0.3 mm (30 Hz, 1 msec, 10-30 V). In non-reserpinized cats, the nigral stimulation caused a decrease in striatal blood flow, increase in cortical blood flow and rise in mean blood pressure. Hexamethonium (3 mg/kg, i.v.) blocked completely the rise in mean blood pressure following nigral stimulation, but did not affect a decrease in striatal blood flow, indicating that a decrease in striatal blood flow following nigral stimulation was not due to the activation of the peripheral sympathetic nervous system. Nigral-induced decrease in striatal blood flow in non-reserpinized cats was blocked by haloperidol (0.1 mg/kg, i.v.), methysergide (1 mg/kg, i.v.) and reserpine (2 mg/kg, i.v.), but not by phentolamine (7 mg/kg, i.v.). In reserpinized cats, nigral stimulation caused an increase in striatal blood flow in contrast to a decrease in non-reserpinized cats. After administration of 5-HTP (50 mg/kg, i.v.) in reserpinized cats, nigral stimulation decreased the striatal blood flow. On the other hand, after administration of L-DOPA (30 mg/kg, i.v.) in reserpinized cats, nigral stimulation increased striatal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877111 TI - Impairment of memory and changes in neurotransmitters induced by basal forebrain lesion in rats. AB - The effect of bilateral electrolytic lesioning of the anterior and posterior parts of the basal forebrain (BF) on learning behavior and changes in neurotransmitters in the central nervous system was investigated in rats. The posterior BF lesion caused more severe impairment than the anterior BF lesion in the acquisition of conditioned avoidance response in a two-way shuttle box. A severe deficit in acquisition of passive avoidance response was produced by the posterior BF lesion. Choline acetyltransferase (CAT) activity was decreased significantly in the parietal cortex but not in the occipital cortex in anterior BF-lesioned rats. However, it was not decreased in posterior BF-lesioned rats. The contents of monoamines in the hippocampus was decreased more significantly by the posterior BF lesion than by the anterior BF lesion. These results suggest that the impairment of memory in posterior BF-lesioned rats may be related mainly to monoaminergic function rather than to cholinergic deficit. PMID- 2877112 TI - [Assessment of the antihypertensive action of Bunitrolol in patients with mild and moderate essential hypertension]. PMID- 2877114 TI - [Three-country meeting in Innsbruck. Exchange of experiences across the borders]. PMID- 2877113 TI - [Treatment of cryptorchism with 3 instead of 10 HCG injections]. PMID- 2877115 TI - Dietary problems of phenylketonuria: effect on CNS transmitters and their possible role in behaviour and neuropsychological function. AB - Thirty years ago it was observed that the synthesis of serotonin, dopamine and norepinephrine was impaired in untreated phenylketonuria (PKU) as judged either by a decreased concentration in the blood or decreased excretion in the urine of these neurotransmitters, or of their metabolites, 5-hydroxyindoleacetic acid (5 HIAA) and homovanillic acid (HVA). Fifteen years later, when early treatment of PKU with a phenylalanine restricted diet was routinely introduced, an inverse relationship was found between phenylalanine levels and the urinary excretion of dopamine and serotonin. An inverse relationship between blood phenylalanine levels and cerebrospinal fluid (CSF) concentrations of HVA and 5-HIAA has repeatedly been reported during the past 10 years. Recently, the effect of the discontinuation of diet in PKU on the synthesis of dopamine, norepinephrine and serotonin has been examined, and the possible relationship between low levels of these neurotransmitters and impaired performance on neuropsychological tests has been evaluated. In some PKU patients the performance on neuropsychological tests of higher integrative function is impaired after discontinuation of diet, especially when blood phenylalanine values exceed 1200 mumol/L, and the patients often complain of lack of concentration and emotional instability. When these patients return to a 'relaxed' phenylalanine restricted, tyrosine enriched diet, the impaired neuropsychological and behavioural functions appear to be reversible. One mechanism may involve an impaired synthesis of dopamine and serotonin, as the improvement is accompanied by an increase in dopamine and serotonin excretion and a significant increase in CSF concentrations of HVA and 5 HIAA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877117 TI - Effect of splenectomy on liver regeneration and polyamine metabolism after partial hepatectomy. AB - The effect of splenectomy on hepatic ornithine decarboxylase (ODC) induction, DNA synthesis, and mitosis of hepatocytes was studied in rat liver after partial hepatectomy. ODC activity markedly increased in the early stages of liver regeneration, and the increase in the activity was significantly enhanced in splenectomized rats. Splenectomy specifically induced ODC since tyrosine aminotransferase and general protein synthesis were not affected. Splenectomy also enhanced increase in hepatic polyamines, DNA synthesis, and mitosis in regenerating liver. The results suggest that splenectomy affects liver regeneration after partial hepatectomy by enhancing induction of ODC activity, which is an important biochemical event in the early stage of liver regeneration. PMID- 2877116 TI - Problems related to diet management of maternal phenylketonuria. AB - Provision of nutritionally complete elemental diets for pregnant women with PKU requires greater knowledge of 'conditionally' essential nutrient requirements than is presently available as well as application of known information. Formulation of elemental products needs to be improved to enhance aroma and taste and to decrease osmolality. Designers of the metal and vitamin components should keep in mind that a major portion (70-80%) of most of these nutrients must be obtained from the elemental products. Thus deletion of suspected essential minerals or vitamins could cause serious deficiencies. On the other hand, knowledge of appropriate ratios that make for improved trace metal absorption should be applied. Clinical nutritionists need to assist patients in selection of foods that are low in binding substances and provide 'conditionally' essential nutrients in adequate amounts. Closer cooperation between clinical nutritionists, nutrition scientists and food technologists should result in improved elemental products for care of pregnant women with PKU. PMID- 2877118 TI - Yeast alpha-factor and somatostatin enhance binding of [3H]estradiol to proteins in rat pancreas and Saccharomyces cerevisiae. AB - Pancreatic tissue contains an [3H]estradiol-binding protein that requires a coligand in the steroid-binding reaction. The endogenous coligand appears to be the tetradecapeptide somatostatin. Yeast alpha-factor, a tridecapeptide pheromone that induces conjugation between haploid cells of opposite mating type, was found to be as effective as somatostatin in enhancing specific binding of [3H]estradiol to partially purified pancreatic protein. Supernatant fractions from yeast cells also contain an [3H]estradiol-binding protein. alpha-Factor can enhance specific binding of [3H]estradiol to such yeast fractions. Somatostatin, somatostatin analogues, and an analogue of alpha-factor enhanced binding of [3H]estradiol but did not inhibit cell growth or induce morphological changes in S. cerevisiae. Thus, it appears that coligand-requiring [3H]estradiol-binding activity and mating in yeast are not directly related. PMID- 2877119 TI - Analysis of the relation between receptor binding affinity and antagonist efficacy of antiglucocorticoids. AB - The biological potencies of four antiglucocorticoids, RU486 (RU), dexamethasone oxetanone (DOX), R5020, and progesterone have been studied with respect to dexamethasone induction of tyrosine aminotransferase (TAT) in rat hepatoma tissue culture (HTC) cells. Their inhibitory effects in whole-cell competition binding studies (at 37 degrees C) and in TAT induction studies were analyzed by Dixon plots and Schild plots, respectively. We show that: In both cases, there is an actual competition of each antiglucocorticoid with the agonist dexamethasone for the same binding site; the two Kd values derived from the two plots are almost identical for each antiglucocorticoid; RU486 can be distinguished from the three other antiglucocorticoids by its high biological efficacy and its high affinity for the glucocorticoid receptor in whole cells at 37 degrees C (identical to its affinity in cytosol at 0 degree C). These results imply that: There is a linear correlation between the antagonist efficacies of antiglucocorticoids and their affinities for the glucocorticoid receptor in whole cells at 37 degrees C; the antagonistic action is solely mediated by competition with the agonist for the receptor binding site; this is verified by the fact that in all cases, in the presence or absence of antiglucocorticoids, a specific TAT induction level was always related to the same level of receptor saturation by the agonist in whole cells; the phenomena responsible for the high antagonist efficacy of RU486 are also responsible for its high affinity in whole cells at 37 degrees C. PMID- 2877120 TI - Evaluation of postoperative flow reserve in internal mammary artery bypass grafts. AB - The internal mammary artery has been advocated for use in bypass grafting owing to its superior long-term patency when compared to saphenous vein grafts. Concern exists that the flow through the internal mammary artery may be inadequate during periods of peak myocardial demand. This flow was investigated in 24 consecutive patients with a mean proximal left anterior descending artery stenosis of 87.5% who were selected for coronary bypass using the internal mammary artery. Within 8 weeks of operation, all were evaluated by exercise thallium 201 scintigraphy. Thallium activity, expressed as a ratio of anteroseptal activity to posterolateral wall activity (or inferior wall activity if the posterolateral wall was deemed abnormal), was 0.97 +/- 0.15. A second group of 25 patients, with normal coronary arteries, was similarly evaluated. The mean septal to posterolateral wall thallium activity ratio for these control patients was 1.0 +/ 0.15. A third group of 26 patients who underwent single-vessel percutaneous transluminal coronary angioplasty of the left anterior descending artery and a fourth group of 28 saphenous vein graft recipients were compared by stress thallium scintigraphy. Thallium 201 activity for the vein graft group (0.96 +/- 0.19) was not significantly different from that for the mammary artery group, whereas the flows obtained with a single attempt at angioplasty were significantly inferior (p less than 0.05). The internal mammary artery provides excellent coronary flow at peak myocardial demand and compares favorably to angioplasty and saphenous vein grafting. PMID- 2877121 TI - Free (aorta-coronary) internal mammary artery graft. Late results. AB - Free internal mammary artery grafts were placed in 156 patients (1971 to 1985). Preoperative clinical and angiographic variables were similar to those of other series of isolated coronary bypass grafts. Of 244 total internal mammary artery grafts, 166 were in the aorta-coronary position and were performed mainly because of unsuitable saphenous veins or to gain additional graft length. One patient (0.6%) died during hospitalization. Perioperative complications included respiratory dysfunction in 16 (10.3%), reoperation for bleeding in 13 (8.0%), stroke in four (2.6%), myocardial infarction in three (1.9%), and wound complications in two (1.3%). Morbidity occurred significantly more often in the 1971 to 1975 period. Subsequently, eight (7%) had reoperation (6 to 158 months; mean 99 months). After a 98 month mean follow-up, the 10 year actuarial survival rate (including all causes of death) was 73.3%. Of 40 free grafts restudied within 18 months of operation, 31 (77%) were patent. The higher rate of early closure is attributed to technical problems early in our experience, especially construction of the aortic anastomosis. However, 32 of 35 (91%) free grafts studied after more than 18 months (mean 94 months) were open. Fifty of 58 (86%) free internal mammary artery grafts placed to the anterior descending coronary artery, seven of nine (78%) to the circumflex, and six of eight (75.0%) to the right coronary artery were patent. Sequential catheterization showed that of 24 free grafts open at 9 months, 24 remained patent at 80 months; when six of these were restudied at 93 months (third catheterization) and two (fourth catheterization) at 125 months, all were patent. These late studies of free internal mammary artery grafts showed no evidence of graft atherosclerosis. Free internal mammary artery grafts, like in situ internal mammary artery grafts, appear to have relative immunity from atherosclerosis. These findings expand the versatility of internal mammary artery grafting and justify wider use of free internal mammary artery grafts. PMID- 2877122 TI - Clinical and angiographic assessment of complex mammary artery bypass grafting. AB - The internal mammary artery has become the coronary bypass graft of choice in recent years because of enhanced long-term patency. Along with this trend, sequential, bilateral, and free mammary grafts have been employed more frequently in an effort to maximize the number of distal internal mammary anastomoses. This approach of maximally using the internal mammary artery (complex mammary grafting) seems logical, but at present little information about patency of the newer types of internal mammary artery grafts is available to justify the more complicated procedures. Over a 15 month period, 207 patients underwent bypass graft angiography from 1 to 32 weeks after operation. This is an 85% restudy rate for a consecutive series of coronary bypass procedures. Patency was defined as complete filling of the graft and distal vessel bypassed. A total of 841 distal vessels were grafted, or 4.1 per patient. The overall patency rate was 91% for 503 distal vein graft anastomoses and 99% for 338 internal mammary artery grafts. Individual patency rates of distal anastomoses, expressed as number patent/total (percent patent), were as follows: simple vein grafts, 262/285 (92%); sequential vein grafts, 196/218 (90%); left internal mammary artery to left anterior descending coronary artery, 109/110 (99%); left internal mammary to circumflex marginal artery, 14/14 (100%); right internal mammary to right coronary artery, 19/20 (95%); right internal mammary to left anterior descending coronary artery, 10/10 (100%); right internal mammary to circumflex marginal artery via transverse sinus, 18/20 (90%); sequential left internal mammary artery to left anterior descending system, 133/134 (99%); sequential left internal mammary to circumflex marginal system, 15/15 (100%); free internal mammary artery, 9/9 (100%); free sequential internal mammary artery, 6/6 (100%). Of the 18 patent transverse sinus right internal mammary grafts to the circumflex marginal artery, three exhibited very slow flow and probably were not functional. The hospital mortality associated with internal mammary revascularizations was 0.4% for nonemergency cases and 3.1% for emergency procedures. On the basis of clinical and postoperative graft patency data, expanded use of more complicated types of mammary grafts seems justified. Function of the right internal mammary graft to the circumflex marginal artery was suboptimal, and this method has been discontinued. All other complex mammary techniques had excellent patency rates as compared to vein grafts, and these differences may become even more significant in the late postoperative period.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2877123 TI - Beta-adrenergic agonist-mediated desensitization in senescent rats. AB - The capacity of senescent rats to develop the catecholamine refractory state was investigated in CDF (F-344) rats of 3 and 24 months of age. Beta-adrenergic receptor number, receptor-agonist affinity, and adenylate cyclase activity in heart membranes were assessed, following the chronic in vivo administration of the beta-adrenergic agonist, metaproterenol. Drug treatment leads to marked myocardial hypertrophy, receptor down-regulation, and reduced isoproterenol stimulated adenylate cyclase activity. The extent of catecholamine-refractoriness was not different in the older rats, indicating the catecholamine desensitization of myocardial beta-adrenergic responsiveness is not impaired in senescence. Receptor agonist affinity and the percent of receptors in the high-affinity state decrease with age. These parameters are further reduced by agonist treatment but to a lesser extent in the older animals. Thus, the effects of age and agonist desensitization are not additive and suggest that aged animals may already be partially desensitized. PMID- 2877124 TI - Age-related osteopenia in the mouse: effects of an H1 blocker, a phenothiazine, and promethazine. AB - Mature and old B6AF1 and B6D2F1 mice were given acidified tap water or promethazine HCl (a phenothiazine with H1 receptor blocking activity), chlorpheniramine (an H1 blocker) or trifluoperazine (a phenothiazine with no H1 blocking activity) in their drinking water, and the effects of these agents on bone mineral content were assessed by intermittently measuring the 24-h whole body retention of Tc 99m methylene diphosphonate (Tc 99m MDP, an indicator of bone metabolism) and at the end of the studies by determining ash weights of femur, ilium and sacrum. It was found that 24-h retention of Tc 99m MDP was elevated in old mice as it is in old osteopenic humans, that promethazine but not chlorpheniramine or trifluoperazine inhibited bone loss in aging mice, and that there was a correlation between decrease in retention of Tc 99m MDP and decreased bone loss. These preliminary results suggest that the ability of promethazine to inhibit age-related bone loss may not be mediated through its action as an H1 blocker or as a phenothiazine. However, more agents of each type need to be tested before this point can be established. PMID- 2877125 TI - Compounds acting on alpha 1- and alpha 2- adrenoceptors: agonists and antagonists. PMID- 2877126 TI - Anxiolytic and anxiogenic drug effects in a novel test of anxiety: are exploratory models of anxiety in rodents valid? PMID- 2877127 TI - Indenolol kinetics versus pharmacodynamics in hypertension. AB - A kinetic model has been employed to compare the duration of the antihypertensive activity of indenolol to its plasma half-life both after single administration and at steady-state. After a 14 day run-in period with placebo, 60 or 120 mg indenolol were given to hypertensive patients I or II grade, according to W.H.O. guidelines, once a day for 14 days. Blood samples were drawn and blood pressure recorded at intervals after the first dose, during treatment and after the last dose of the compound. Both plasma concentration and mean arterial pressure difference curves were fitted by a first order input-output model, where plasma half-life was 4 h, while pharmacological half-life was 24 h for both dose-levels tested. Therefore, with once-a-day dose regimen an accumulation of the antihypertensive effect of indenolol was demonstrated, with 99% steady-state of blood pressure reached after 7 days, while the drug did not accumulate in the central compartment. PMID- 2877128 TI - Serum cholesterol, blood pressure, and mortality: implications from a cohort of 361,662 men. AB - The risks associated with various levels of serum cholesterol were determined by analysis of 6-year mortality in 361,662 men aged 35-57. Above the 20th percentile for serum cholesterol (greater than 181 mg/dl, greater than 4.68 mmol/l), coronary heart disease (CHD) mortality increased progressively; the relative risk was large (3.8) in the men with cholesterol levels above the 85th percentile (greater than 253 mg/dl, greater than 6.54 mmol/l). When men below the 20th cholesterol percentile were used as the baseline risk group, half of all CHD deaths were associated with raised serum cholesterol concentrations; half of these excess deaths were in men with cholesterol levels above the 85th percentile. For both CHD and total mortality, serum cholesterol was similar to diastolic blood pressure in the shape of the risk curve and in the size of the high-risk group. This new evidence supports the policy of a moderate fat intake for the general population and intensive treatment for those at high risk. There is a striking analogy between serum cholesterol and blood pressure in the epidemiological basis for identifying a large segment of the population (10-15%) for intensive treatment. PMID- 2877129 TI - Effects of synvinolin (MK-733) on plasma lipids in familial hypercholesterolaemia. AB - The effects of synvinolin (MK-733), a competitive inhibitor of 3-hydroxy-3 methylglutaryl coenzyme A reductase, were investigated in 43 patients with heterozygous familial hypercholesterolaemia in a double-blind, placebo controlled, dose-finding study. Synvinolin was given in doses ranging from 2.5 mg to 80 mg per day for 4 weeks. 8 patients received placebo. Low-density lipoprotein cholesterol fell on average by 18% on 2.5 mg/day and 42% on 80 mg/day. The drug was as effective whether it was given once or twice daily. Serum high-density-lipoprotein cholesterol tended to increase and serum triglycerides to decrease on the higher doses. The drug was tolerated well. Except for a slight rise in alanine aminotransferase in 3 patients no objective side-effects were observed. PMID- 2877131 TI - Transdermal testosterone substitution therapy for male hypogonadism. AB - A transdermal therapeutic system (TTS) for administration of testosterone was tested in healthy and hypogonadal men. To ensure adequate absorption, a testosterone-loaded film was applied to the scrotal skin. The TTS was designed to last for 22 h; over this time serum testosterone levels in normal men were moderately increased, with concentration curves almost parallel to basal levels. Seven hypogonadal patients also responded to TTS testosterone; serum testosterone levels were in the normal range during a 12-week treatment period. There were no side-effects. TTS testosterone offers a new approach to androgen substitution therapy. PMID- 2877130 TI - Sympathetic tone modulates portal venous pressure in alcoholic cirrhosis. AB - Sixteen alcoholic cirrhotic patients with portal hypertension were studied before and after 2.5 micrograms/kg intravenous clonidine. In six patients portal venous pressure was assessed simultaneously by wedged hepatic vein and transhepatic portal vein cannulation. Wedged hepatic vein pressure accurately reflected portal venous pressure both before and after clonidine (r = 0.912 and 0.940; p less than 0.01). In all the other ten patients, sympathetic tone, measured by total plasma noradrenaline spillover, was high (755 +/- 123 ng/min; normal 296 +/- 29 ng/min). It fell significantly after clonidine (378 +/- 95 ng/min; p less than 0.01). This fall was associated with a decrease in corrected wedged hepatic vein pressure (18.6 +/- 1.1 to 13.4 +/- 0.5 mm Hg; p less than 0.01) but no change in estimated hepatic blood flow (934 +/- 94 to 976 +/- 102 ml/min), indicating a fall in postsinusoidal hepatic vascular outflow resistance. Clonidine-induced changes in mean arterial pressure and cardiac output were independent of the change in portal venous pressure. The results suggest that in alcoholic cirrhosis there is a labile component of hepatic vascular resistance which is partly under sympathetic nervous control and is thus potentially sensitive to pharmacological control. PMID- 2877132 TI - Clinical experience with 99mTc-hexamethylpropylene-amineoxime for labelling leucocytes and imaging inflammation. AB - Hexamethylpropylene-amineoxime (HMPAO) forms a lipid-soluble neutral complex with 99mTc which is rapidly incorporated into leucocytes in vitro. In six patients with suspected or known inflammatory disease, a "mixed" leucocyte suspension isolated from 85 ml blood anticoagulated with acid-citrate-dextrose was labelled by 99mTc-HMPAO with a mean efficiency of 47% (SE2%), of which 78% (3) was taken up by granulocytes. Activity eluted more rapidly from other cell types in vitro than from granulocytes, which remained firmly labelled. Mean initial biodistribution of the label and granulocyte recovery in blood of 32% (8) at 30 40 min showed that the granulocytes were not significantly activated during labelling. All six patients were positive for inflammatory disease, as early as 30 min in five patients and at 3 h in the sixth; they all remained positive at 20 24 h. Four patients also received 111In-labelled "pure" granulocytes. In terms of detail, the 99mTc images were comparable or superior to the 111In images. PMID- 2877133 TI - Who will get AIDS? PMID- 2877134 TI - Catatonia. PMID- 2877135 TI - Academic medicine and the NHS: a partnership in jeopardy. PMID- 2877136 TI - Diagnosis of right ventricular myocardial infarction. PMID- 2877137 TI - Obstetric hysterectomy. PMID- 2877138 TI - Hypersensitivity to sulphonamides--a clue? PMID- 2877139 TI - Assessment of dysphonia. PMID- 2877140 TI - Bone-marrow autotransplantation in man. Report of an international cooperative study. AB - Bone-marrow autotransplantation consists of the administration of extremely high doses of chemotherapy and/or radiation followed by "rescue" with autologous, cryopreserved, bone-marrow cells. This approach can produce responses unattainable with conventional doses of similar agents. Bone-marrow autotransplantation is increasingly being done. This report summarises data from 2570 patients receiving autotransplants at 43 centres worldwide for haematological malignancies and solid tumours; more than 50% of these transplants were done since 1984. Most transplants were performed for treatment of lymphoma, leukaemia, lung cancer, melanoma, neuroblastoma, and breast cancer. Preliminary analyses indicate favourable responses in some tumour types and provide a basis for future investigations. PMID- 2877141 TI - Treatment of end-stage renal failure due to diabetes in the United Kingdom, 1975 84. AB - In 1975-84 762 new patients with end-stage renal failure (ESRF) due to diabetes mellitus were accepted onto renal replacement programmes in the United Kingdom. They formed 5.7% of the total intake of ESRF patients. This proportion rose from 1.4% in 1975 to 11.1% in 1984. 4.1% of the patients on renal replacement therapy at the end of 1984 were reported as having ESRF due to diabetic nephropathy. During 1983-84, 272 patients taken on were type I (76%) and 87 (24%) were type II diabetics. Continuous ambulatory peritoneal dialysis (CAPD) was most popular as both initial (51%, plus 24% on intermittent peritoneal dialysis in 1983-84) and long-term treatment (48% of 446 under treatment at Dec 31, 1984); 163 patients (36.5%) had successful allografts, and only 14% of patients were on haemodialysis. Actuarial survival was 49% at 3 years, irrespective of type of treatment; the death rate for type II diabetics approached the intake rate in 1983-84. There was considerable regional variation in the numbers of diabetics on treatment. Even though the proportion of diabetics entering British end-stage renal failure programmes is rising, many patients who may benefit from treatment are probably not receiving it. PMID- 2877142 TI - Legionella micdadei pneumonia in normal hosts. PMID- 2877143 TI - Lymphoblastic leukaemia in Siamese twins: evidence for identity. PMID- 2877144 TI - Levodopa treatment may benefit or impair "frontal" function in Parkinson's disease. PMID- 2877146 TI - Broad-complex tachycardias. PMID- 2877145 TI - Topical cyclosporin in alopecia areata and nickel contact dermatitis. PMID- 2877147 TI - Heterosexual transmission of hepatitis B virus from symptomless HBsAG carriers positive for anti-HBe. PMID- 2877148 TI - Failure of high intrauterine insemination of husband's semen. PMID- 2877149 TI - Teicoplanin-resistant coagulase-negative staphylococcus. PMID- 2877150 TI - Central venous catheterisation. PMID- 2877151 TI - Polymyositis and molecular mimicry. PMID- 2877152 TI - Campylobacter-like organisms and acute purulent gastritis. PMID- 2877153 TI - Coronary revascularisation by percutaneous transluminal coronary angioplasty for recurrent ischaemic pulmonary oedema. PMID- 2877154 TI - Where will this month's medical school intake go? PMID- 2877155 TI - Knee moments in Duchenne muscular dystrophy. PMID- 2877156 TI - Preponderance of females with AIDS in Ghana. PMID- 2877157 TI - Oral hairy leucoplakia in two women, a haemophiliac, and a transfusion recipient. PMID- 2877158 TI - AIDS and promiscuity. PMID- 2877159 TI - Place of IgM antibody testing in HIV serology. PMID- 2877161 TI - Rewarming patterns in upper limbs. PMID- 2877160 TI - Anti-phospholipid antibodies and pregnancy wastage. PMID- 2877163 TI - Carboplatin chemotherapy for malignant paraganglioma. PMID- 2877162 TI - Failure of mineral supplementation to reduce incidence of rickets in very-low birthweight infants. PMID- 2877164 TI - False-positive ELISA for Chlamydia trachomatis recognised by atypical morphology on fluorescent staining. PMID- 2877165 TI - HLA-D region antigen expression on stomach epithelium in absence of autoantibodies. PMID- 2877167 TI - Reinfection with Borrelia burgdorferi. PMID- 2877166 TI - Pulsed Doppler diagnosis of cerebral air embolus in a baby with pulmonary interstitial emphysema. PMID- 2877168 TI - Differential diagnosis of motoneurone disease from other neurological conditions. PMID- 2877169 TI - When should levodopa be started? PMID- 2877170 TI - Cervical smears: choice of spatula is critical. PMID- 2877171 TI - Ifosfamide/mesna nomogram and serum albumin. PMID- 2877172 TI - Identification of HLA-Dw14 genes in DR4+ rheumatoid arthritis. AB - Genes of the major histocompatibility complex, HLA, are associated with susceptibility to rheumatoid arthritis (RA), but the aetiology of this chronic inflammatory disease is not known. Synthetic oligonucleotide DNA probes were constructed to distinguish between two closely related but distinct alleles encoding the HLA-DR4 specificity in patients with RA. With these allele-specific oligonucleotide probes an uncommon DR4 genetic variant, Dw14, was identified in 6 of 7 RA patients homozygous for HLA-DR4. This allele may play an important part in susceptibility to RA. PMID- 2877173 TI - Coronary artery surgery with patient's lungs as oxygenator. AB - The use of the patient's own lungs as oxygenator was assessed during coronary artery bypass grafting in 20 patients. This technique maintained the circulation and provides excellent oxygenation, and the lungs did not intrude on the operative field. Blood damage as assessed by platelet function and lung sequestration was less than that reported with other forms of bypass. No microbubbles were produced, since there was no artificial blood/air interface. Complement activation, as assessed by amount of white-cell sequestration in the lungs, was also lower than that reported in other forms of bypass. There were no major complications attributable to the technique. Apart from being substantially cheaper than conventional cardiopulmonary bypass, the use of the patient's lungs as oxygenator offers the potential advantage of reduced trauma to the blood and merits further consideration. PMID- 2877174 TI - Characteristics of a glutamine carrier in skeletal muscle have important consequences for nitrogen loss in injury, infection, and chronic disease. AB - A carrier for glutamine, identified in rat muscle, has properties in terms of kinetics, ion dependence and hormone sensitivity, and effects of endotoxin and branched-chain aminoacids that point to an important function in the control of whole-body aminoacid metabolism. The existence of a link between the size of the glutamine pool in muscle and the rate of muscle protein synthesis raises possibilities for therapeutic interventions to limit protein loss in injury, sepsis, and chronic disease. PMID- 2877175 TI - Peptic ulceration: the eye of the cyclone. PMID- 2877176 TI - LHRH analogues in endometriosis. PMID- 2877177 TI - The natural laboratory. PMID- 2877178 TI - Advertising during anaesthesia? PMID- 2877179 TI - Science and the public. PMID- 2877180 TI - The parasomnias. AB - Parasomnias are due to a combination of familial, developmental, and environmental factors. The clinical features are well known, but reports by patients do not always match the typical descriptions. Parasomnias are not due to mental ill-health but are occasionally associated with brain disease. Their recognition is important, but treatment is rarely necessary. Occasionally, life threatening injuries result from sleep-walking and night terrors. PMID- 2877181 TI - The Trieste experience. PMID- 2877182 TI - Second-generation clinical pharmacology. PMID- 2877183 TI - Anaesthesia for children. PMID- 2877184 TI - Prevention of catheter-associated urinary-tract infections by use of silver impregnated catheters. PMID- 2877185 TI - Safety of human and ovine corticotropin-releasing hormone. PMID- 2877186 TI - Acetaldehyde modification of proteins as result of ethanol metabolism. PMID- 2877187 TI - Toxic psychosis from transdermal scopolamine in a child. PMID- 2877188 TI - Safety of dipyrone. PMID- 2877189 TI - Give a drug a bad name: cinnarizine. PMID- 2877190 TI - Prevalence of undiagnosed syphilis in the elderly. PMID- 2877191 TI - Consequences of Chernobyl accident for health services. PMID- 2877192 TI - In-vitro sensitivity of Campylobacter pyloridis to furazolidone. PMID- 2877193 TI - Sensitivity to albendazole sulphoxide of Echinococcus granulosus scoleces in man. PMID- 2877195 TI - Thyroid-stimulating hormone measurements by immunoradiometric assay in severely ill patients. PMID- 2877194 TI - Mechanism of action of adjuvant chemotherapy in early breast cancer. PMID- 2877196 TI - Fulminant hepatic failure treated by hepatic transplantation. PMID- 2877197 TI - Papillomavirus infections in women. PMID- 2877198 TI - Tobacco and asbestos litigation. PMID- 2877199 TI - Tobacco: UK and China. PMID- 2877200 TI - Assault rates and unemployment. PMID- 2877201 TI - B-cell lymphomas in two HIV seropositive heroin addicts. PMID- 2877202 TI - Subacute polyneuropathy with encephalopathy in AIDS with human cytomegalovirus pathogenicity? PMID- 2877203 TI - IgA deficiency and salivary transmission of human immunodeficiency virus. PMID- 2877204 TI - AIDS information. PMID- 2877205 TI - Apolipoprotein CIII polymorphism and coronary heart disease. PMID- 2877206 TI - Persistence of vaginal vault granulation. PMID- 2877207 TI - Diastolic versus systolic. PMID- 2877208 TI - Erythema nodosum provoked by hepatitis B vaccine. PMID- 2877209 TI - Metoprolol and albumin excretion in diabetes. PMID- 2877210 TI - Isolation of Escherichia coli O157:H7 from dairy cattle associated with two cases of haemolytic uraemic syndrome. PMID- 2877212 TI - Prognostic factors in myelodysplastic syndromes. PMID- 2877211 TI - Chloroquine-resistant falciparum malaria in Benin. PMID- 2877213 TI - Aspirin-like analgesics and cataract. PMID- 2877214 TI - Mammillary fistula. PMID- 2877215 TI - Retrovirus and Kawasaki disease. PMID- 2877216 TI - Colonoscopy and barium enemas. PMID- 2877217 TI - Heparin and mast cells. PMID- 2877218 TI - Transplants of primate neurons. PMID- 2877219 TI - Metabolic epidemiology of plasma cholesterol. Mechanisms of variation of plasma cholesterol within populations and between populations. International Collaborative Study Group. AB - Plasma cholesterol concentrations vary widely within and between populations, underlying a broad range of coronary heart disease mortality. Since the metabolic bases of this variation are poorly understood, low-density lipoprotein (LDL) metabolism was investigated, kinetically and in vitro, in five population samples from nutritionally disparate countries; 109 men with LDL cholesterol 1.0-6.7 mmol/l were studied. Slow production rate and rapid fractional catabolism, possibly due to high LDL receptor activity, underlay the lowest LDL cholesterol levels within each population; highest levels were largely maintained by rapid production rate. Differences in production rate explained more of the variation in LDL cholesterol than differences in fractional catabolic rate. Very low LDL levels in the African subjects were due to slow production rate; differences in fractional catabolic rate and production rate interacted in determining levels in the European populations. Direct relations were present between saturated fatty acid intake and production rate, and between monounsaturated fatty acid intake and fractional catabolic rate, and may contribute to differences in LDL metabolism between populations. PMID- 2877220 TI - A psychiatric study of idiopathic oedema. AB - Twenty-five women with idiopathic oedema and twenty-five women attending gynaecology clinics were assessed by means of a standardised psychiatric interview, an interview on dietary habits, and a specially designed interview on current health. The patients with idiopathic oedema were significantly more depressed and anxious, with a trend towards widespread neurotic symptoms. There was no evidence that diuretic or laxative abuse is an important aetiological factor. In many patients with idiopathic oedema excessive fluid retention may be related to the neuroendocrine abnormalities associated with psychiatric illness. PMID- 2877221 TI - Influence of sleep disruption and calorie restriction on biological markers for depression. AB - The hypothesis that the dexamethasone suppression test (DST) and rapid-eye movement (REM) latency test are not biological markers for depressive illness but artifacts arising from dietary and sleep disturbances that accompany depression was examined in 28 normal volunteers. The restriction of calorie intake with moderate weight loss reproduced a pattern of response to dexamethasone closely resembling that claimed to be diagnostic of depressive illness. The shortened REM latencies claimed as a diagnostic marker were replicated in volunteers by mimicking the sleep pattern commonly found in depression. These changes could not be explained by the induction of mood disorder in the subjects. The results put in question the diagnostic value of the DST and REM latency tests in clinical practice, where sleep disorder and poor appetite, with reduced calorie intake, are the common accompaniments of depressive illness. PMID- 2877222 TI - Effect of cyclophosphamide therapy on oncogene expression in angioimmunoblastic lymphadenopathy. AB - The expression of four cellular oncogenes was studied by means of northern blot analysis of messenger RNA in peripheral-blood mononuclear cells from patients with angioimmunoblastic lymphadenopathy (AILD). On average, cells from patients with AILD and from those with systemic lupus erythematosus (SLE) expressed significantly more N-ras and significantly less c-fos mRNA than did cells from healthy controls. Expression of these cellular oncogenes was most abnormal in patients with the most severe disease. In contrast, increased levels of c-myc mRNA were found in patients with SLE but not in those with AILD. Administration of cyclophosphamide to patients with AILD was followed by return to normal of both N-ras and c-fos expression. PMID- 2877223 TI - Prevention of graft failure by an anti-HLFA-1 monoclonal antibody in HLA mismatched bone-marrow transplantation. AB - Seven patients with immunodeficiencies (Wiskott-Aldrich syndrome, combined immunodeficiency, and osteopetrosis) were given a mouse monoclonal antibody against the alpha subunit of human leucocyte functional antigen (HLFA-1; CD18) to facilitate the engraftment of mismatched haploidentical related-donor bone marrow. Other conditioning included busulphan, cyclophosphamide, and antilymphocyte globulin. To prevent graft-versus-host disease the bone-marrow T cells were depleted with sheep erythrocyte rosetting and cyclosporin therapy was given. HLFA-1 antibody injections were well tolerated without side-effects except slight, transient fever (38-40 degrees) after the first injection. Engraftment was rapid in all seven patients. The regenerating leucocytes were of donor origin in all cases, and two patients have a mixed chimera. Two patients died from infections. The others are alive and well 60-395 days after transplantation. In a historical control group given the same treatment without anti-HLFA-1 infusion, only one of seven transplants partially engrafted; only two patients remain alive with autologous reconstitution but with uncorrected immunodeficiency. PMID- 2877224 TI - The colostomy plug: a new disposable device for a continent colostomy. AB - A new disposable device for colostomy control is described. It is a two-piece system consisting of an adhesive base plate and a disposable colostomy plug, attachable to the plate. The plug is made of a soft, pliable plastic material with open cells, containing a carbon filter which allows flatus to pass odour free. It is packed and compressed in a water-soluble film, which disintegrates immediately after insertion, allowing the plug to expand and prevent the passage of faeces. The device has been tested in 53 patients. Faecal continence and the passage of flatus without noise or odour was achieved in 90%. The median application period until the plug became obstructed with mucus or faeces was 8 h (range 5-24 h or more), the application period being somewhat longer for patients who used bowel irrigation. Patients not using bowel irrigation applied a colostomy bag during the night. PMID- 2877225 TI - Quantification of cerebral oxygenation and haemodynamics in sick newborn infants by near infrared spectrophotometry. AB - New apparatus was made whereby indices of cerebral oxygenation and haemodynamics in sick newborn infants could be quantified by near infrared (NIR) spectrophotometry and displayed instantaneously at the cotside. The indices included oxygenated haemoglobin, reduced haemoglobin, oxidised cytochrome aa3, and total haemoglobin concentration: cerebral blood volume, mixed cerebral venous saturation, and changes in cerebral blood flow were then derived. Striking changes were observed in response to alterations in arterial oxygen saturation and carbon dioxide tension and to tilting of the infant. Abnormal responses were detected in cerebral oedema following birth asphyxia, patent ductus arteriosus, and cystic encephalomalacia. NIR spectrophotometry provides valuable quantitative data at the cotside for the management of sick infants and for exploring the pathophysiology of damage to the brain. PMID- 2877226 TI - Lathyrism: evidence for role of the neuroexcitatory aminoacid BOAA. AB - Lathyrism, a form of motoneuron disease induced by excessive consumption of th legume Lathyrus sativus (chickling pea), presents as signs of pyramidal tract involvement. Primate feeding studies show that beta-N-oxalylamino-L-alanine (BOAA), a potent neuroexcitatory aminoacid in the chickling pea, induces corticospinal dysfunction similar to that seen in animals consuming a fortified diet of this legume. BOAA, a potent agonist of the excitatory neurotransmitter glutamate, is likely to be causally associated with lathyrism in man. PMID- 2877228 TI - Sudden infant death and inherited disorders of fat oxidation. PMID- 2877227 TI - Alzheimer's disease, Parkinson's disease, and motoneurone disease: abiotrophic interaction between ageing and environment? AB - The hypothesis is that Alzheimer's disease, Parkinson's disease (PD), and motoneurone disease are due to environmental damage to specific regions of the central nervous system and that the damage remains subclinical for several decades but makes those affected especially prone to the consequences of age related neuronal attrition. This proposal is based on the association between environmental factors and certain neurodegenerative diseases (eg, methylphenyltetra-hydropyridine and parkinsonism, poliovirus infection and post poliomyelitis syndrome, chickling pea ingestion and lathyrism, an unidentified environmental factor and amyotrophic lateral sclerosis-PD complex of Guam, and trauma and pugilist's encephalopathy) and on the long latent period between exposure to environmental factor and the appearance of symptoms in some of these disorders. The practical implications of this hypothesis are that epidemiological attention should be focussed on the environment in early rather than late life, prevention may be a realistic goal if the cause of subclinical damage can be identified, a search should be undertaken for causal mechanisms linking subclinical neuronal damage due to an environmental factor and the normal ageing process, and (4) better understanding of the regional selective vulnerability of the nervous system to the ageing process might allow a rational approach to treatment. PMID- 2877230 TI - Causes and consequences of hand injury. PMID- 2877229 TI - Risks of antihypertensive therapy. PMID- 2877231 TI - Presentation of myocardial infarction in the elderly. PMID- 2877232 TI - Local formularies--the way ahead. PMID- 2877233 TI - Acromioclavicular dislocations: conservative treatment vindicated. PMID- 2877235 TI - Prostaglandins for peptic ulcer: a promise unfulfilled. AB - Prostaglandin analogues appear to heal peptic ulcers no better than would be predicted from their ability to inhibit acid secretion. This implies that their cytoprotective properties, which are so dramatic in acute animal experiments, play no part in ulcer healing. Ulcer healing involves mucosal repair, whereas cytoprotection concerns preservation of normal mucosa, the two processes being conceptually different. If any general benefits of prostaglandin cytoprotection are to be harnessed to clinical ends, drug delivery systems that ensure long lasting contact with the gastroduodenal mucosa may be needed. PMID- 2877234 TI - Bone-marrow transplantation for immunodeficiencies and osteopetrosis: European survey, 1968-1985. AB - In this retrospective analysis of allogeneic bone-marrow transplantation (BMT) carried out between 1969 and 1985 at fourteen European centres in 162 patients with sixteen different types of inherited immunodeficiencies and osteopetrosis, the overall survival with functional grafts was 51.7% (85 patients), with a minimum follow-up of 5 months. In patients with severe combined immunodeficiency HLA-matched (n = 41) and T-cell-depleted HLA-mismatched BMT (n = 46) resulted in 68% and 57% disease-free survival, respectively; after HLA-mismatched transplants, older age (greater than 6 months) and adenosine-deaminase deficiency resulted in poorer survival. Eight other lethal immunodeficiencies, including profound T-cell deficiencies, Wiskott-Aldrich syndrome, Kostmann syndrome, LFA 1/CR 3/p150,95 deficiency, and Chediak-Higashi syndrome as well as malignant osteopetrosis, have been successfully treated by BMT. In this group, survival with functional graft was 47% with HLA-matched and 29% with T-cell-depleted HLA mismatched BMT. Engraftment failure was the major complication in this group. Poorer prognosis was associated with older patients, profound T-cell deficiencies, and the degree of HLA incompatibility. PMID- 2877236 TI - The RAWP review: pious hopes. Resource Allocation Working Party. PMID- 2877237 TI - Human papillomavirus genomes in penile smears of healthy men. PMID- 2877238 TI - Cyclosporin and Raynaud phenomenon. PMID- 2877239 TI - Sudden death in sleep of South-East Asian refugees. PMID- 2877240 TI - Enalapril-induced cough. PMID- 2877241 TI - Is pneumonia developing in patients in intensive care always a typical "nosocomial" infection? PMID- 2877242 TI - Combination therapy in prostate cancer. PMID- 2877243 TI - Trace metals and plasma exchange. PMID- 2877244 TI - Nitrogen dioxide and asthma outbreaks. PMID- 2877245 TI - Hypoxia of altitude. PMID- 2877247 TI - Alzheimer's disease and tau proteins. PMID- 2877246 TI - Immunosuppressive drugs in diabetes. PMID- 2877248 TI - Mobilisation of lead from adipose tissue and cisplatin therapy. PMID- 2877249 TI - Paroxysmal nocturnal haemoglobinuria and pregnancy. PMID- 2877250 TI - Post-transfusion graft-versus-host disease after open heart surgery. PMID- 2877251 TI - Examination of the anus in suspected child sexual abuse. PMID- 2877252 TI - Services for the mentally handicapped. PMID- 2877253 TI - Informed consent. PMID- 2877254 TI - Opisthotonos and benzodiazepine withdrawal in the elderly. PMID- 2877255 TI - Increased sexual function in benzodiazepine withdrawal. PMID- 2877257 TI - Valproate or infective hepatitis? PMID- 2877256 TI - Ifosfamide/mesna nomogram and serum albumin. PMID- 2877258 TI - Diuretics in heart failure. PMID- 2877260 TI - Misdiagnosis of ventricular tachycardia. PMID- 2877259 TI - Bedside theophylline assay in management of severe acute asthma. PMID- 2877261 TI - Are medical injections a risk factor for HIV infection in children? PMID- 2877262 TI - Reassessment of predicted numbers of AIDS cases in the UK. PMID- 2877263 TI - AIDS and Hodgkin's disease. PMID- 2877264 TI - Toxicity of antidepressants. PMID- 2877265 TI - Calcium and blood pressure. PMID- 2877266 TI - Is homoeopathy a placebo response? PMID- 2877267 TI - Changes in brain water with haemodialysis. PMID- 2877268 TI - Intermittent pneumatic compression in healing of venous ulcers. PMID- 2877270 TI - Cerebral artery Doppler ultrasonography for prediction of outcome after perinatal asphyxia. AB - 43 term infants with clinical neurological manifestations of intrapartum asphyxia and who survived for more than 2 days were studied sequentially, while in hospital, with doppler ultrasound examination of the anterior cerebral arteries. 36 survivors with post-asphyxial encephalopathy were followed up for a median of 18 months and none who had had normal doppler measurements (defined by results in 49 non-asphyxiated babies) became seriously handicapped. Of the 18 infants with abnormal waveforms 12 had an adverse outcome (death or handicap). In the asphyxiated infants, doppler examination predicted outcome with an accuracy of 86%. The prediction of adverse outcome by abnormal doppler showed a sensitivity of 100% and a specificity of 81%. All abnormal results had occurred by 62 hours from birth. PMID- 2877269 TI - Evidence for heterosexual transmission and clinical manifestations of human immunodeficiency virus infection and related conditions in Lusaka, Zambia. AB - In a hospital-based survey in Lusaka, Zambia, 189 (17.5%) of 1078 subjects had antibodies against the human immunodeficiency virus (HIV). The prevalence of antibodies was low in subjects aged less than 20 or greater than 60 years; in men the peak prevalence (32.9%) occurred in those aged 30-35 years, and in women (24.4%) it occurred in the 20-25 year age-group. There was no significant difference in prevalence by sex after adjusting for age. High educational level was independently associated with HIV seropositivity; the antibody against HIV was found in 18.4% of blood donors and in 19.0% of hospital workers. Among patients the antibody prevalence ranged from 8.7% in antenatal women and 9.3% in orthopaedic patients to 29.2% in those attending sexually transmitted disease (STD) clinics (the prevalence being 37.3% in previous attenders and 22.8% in first-time attenders). Seropositivity rates were higher in patients with an infectious problem (23.4%) than in those without (11.4%, p = 0.0002). Herpes zoster, oral thrush, diarrhoea, tuberculosis, and weight loss were independently correlated with seropositivity. The data strongly suggest that HIV infection is prevalent in Africa and is transmitted heterosexually. The restricted distribution of seropositivity to the sexually active age-groups indicates that the epidemic, at least in this part of Africa, is newly introduced; this has substantial implications for prevention. PMID- 2877271 TI - Relation of fetal hypoxia in growth retardation to mean blood velocity in the fetal aorta. AB - Umbilical venous blood pO2, pCO2, pH, erythroblast count, and plasma lactate were measured in twenty-nine fetuses with growth retardation. There were significant negative correlations between the severity of fetal hypoxia, hypercapnoea, acidosis, and hyperlactaemia and the mean velocity of blood in the fetal aorta measured by doppler ultrasound. PMID- 2877272 TI - Aortic calcification as a predictor of cardiovascular mortality. AB - Since aortic calcification is seen on X-rays of the prelumbar region in many patients, its relation with cardiovascular disease (CVD) was investigated in a prospective study in The Netherlands. X-rays were taken of 1359 men and 1598 women, in 1975-78. In the subsequent 9 years, 50 men and 33 women died from CVD. The prevalence of aortic calcification was about 10% in middle-aged subjects and rose with age to a maximum of 45% in men and 75% in women. Aortic calcification was associated with a six-fold increased risk of CVD death in men aged 45 years, independent of major CVD risk factors. For each year of age over 45, risk associated with the presence of aortic calcification declined by 6%. Death rates in middle-aged women were too small for risk analysis. These results suggest that atherosclerosis in other than coronary or cerebral vessels may have predictive relevance for CVD death: its diagnosis indicates intervention on present CVD risk factors. PMID- 2877273 TI - A second site for Epstein-Barr virus shedding: the uterine cervix. AB - Epstein-Barr virus (EBV) infection of the human uterine cervix was detected in 5 out of 28 women by means of culture and cytohybridization analysis of cervical secretions. Cervical samples from 2 of 14 women contained epithelial cells with EBV DNA, and filtered cervical washings from 4 women contained infectious EBV. The discovery of EBV shedding in its cell-free infectious form from the uterine cervix raises the possibility of venereal transmission, neonatal infection, and EBV involvement in cervical pathology. PMID- 2877276 TI - Akathisia and antipsychotic drugs. PMID- 2877275 TI - Role of plasma exudation in asthmatic airways. AB - In normal airway defence and especially in asthma, mediators released from inflammatory cells will directly affect the walls of the abundant airway microvessels, making them much more permeable to macromolecules. Through large gaps between actively separated (contracted?) endothelial cells of venules of the tracheobronchial circulation, there is a bulk flow of proteinaceous plasma. The plasma exudate is distributed in the airway wall and it readily passes across an inflamed mucosa into the airway lumen. Plasma in the airway wall causes oedema, which may result in hyperresponsiveness and epithelial shedding. In the lumen its effects are formation of mucus plugs and inhibition of mucociliary transport, and its potent mediators such as the protein products of the kinin, complement, and clotting systems are released. Thus plasma exudation may operate in several aspects of asthmatic diathesis. By positive feedback mechanisms and recruitment and conditioning of inflammatory cells plasma exudate may amplify the inflammatory process. PMID- 2877277 TI - On three stages of amoebic research. PMID- 2877274 TI - Successful treatment of Diphyllobothrium latum and Taenia saginata infection by intraduodenal 'Gastrografin' injection. AB - Tapeworm infections are very difficult to cure completely. Thirteen patients with tapeworm infection, seven with Diphyllobothrium latum and six with Taenia saginata, were treated by the introduction of a radio-opaque contrast medium, 'Gastrografin', into the duodenum through a duodenal tube. The whole tapeworm with the scolex was expelled unfragmented within 1 h in eleven cases. One patient expelled a tapeworm 3 days after treatment; the peristalsis of his intestine had been severely disturbed after an attack of cerebral apoplexy. The tapeworm could not be expelled by the remaining patient, probably because she had severe intestinal adhesion. The injection of gastrografin allowed clear visualisation of the tapeworm, the diagnosis of the infection could be confirmed, and the descent of the tapeworm could be observed serially. This treatment had no serious adverse effects in any of out patients. PMID- 2877278 TI - EBV and the uterine cervix. PMID- 2877279 TI - Molecular biology of the DMD locus. PMID- 2877280 TI - Collagenous colitis. PMID- 2877281 TI - Mechanism of the third heart sound. PMID- 2877282 TI - Nationwide epidemic of Kawasaki disease in Japan during winter of 1985-86. AB - Surveillance data on Kawasaki disease from 148 representative hospitals throughout Japan revealed a third nationwide epidemic of Kawasaki disease in Japan in November, 1985. The peak number of cases was at least 4.5 times greater than that observed in the preceding year. This epidemic wave spread from central Japan to the entire nation within six months. PMID- 2877283 TI - Answers to ten questions on the dietary treatment of chronic renal failure: On behalf of the Steering Committee of the European Study Groups for the Conservative Treatment of Chronic Renal Failure. PMID- 2877284 TI - Seven-year study of hepatitis B vaccine efficacy in infants from an endemic area (Senegal). AB - A booster dose of hepatitis B vaccine was given to 143 children in whom hepatitis B had not developed 1 year after initial vaccination. Over the next six years the incidence of hepatitis B in this group was 1.5% per year compared with 11.5% per year in a similar group of unvaccinated children. In the first 4 years the protective efficacy of the vaccine was 100%, but during the 5th and 6th years it fell to 67%. For maximum protection a second booster is needed, 5 years after the first. PMID- 2877285 TI - Epidemiology of ophthalmia neonatorum in Kenya. AB - In a Nairobi hospital where ocular prophylaxis against ophthalmia neonatorum has been discontinued, 1,019 women were screened for Neisseria gonorrhoeae and Chlamydia trachomatis during labour and 7 and 28 days postpartum. The prevalence of gonococcal infection was 7% and that of chlamydial was 29%. 52.4% of gonococcal isolates produced penicillinase. The incidence of ophthalmia neonatorum was 23.2 per 100 live births, and incidences of gonococcal and chlamydial ophthalmia were 3.6 and 8.1 per 100 live births, respectively. Of 181 cases of neonatal conjunctivitis, 31% were caused by C trachomatis, 12% by N gonorrhoeae, and 3% by both. In 67 babies exposed to maternal gonococcal infection and 201 exposed to maternal chlamydial infection, rates of transmission to the eye were 42% and 31%, respectively, and to the throat were 7% and 2%. Gonococcal transmission rate was higher in mothers with concomitant chlamydial infection (68%; p = 0.01). Postpartum endometritis was associated with ophthalmia neonatorum (p less than 0.001). Ocular prophylaxis at birth for gonococcal ophthalmia should be reintroduced. PMID- 2877286 TI - Confidentiality: the slackness of doctors. PMID- 2877287 TI - Persistent eye watering among Bhopal survivors. PMID- 2877288 TI - Gamete intrafallopian transfer in a non-IVF unit. PMID- 2877290 TI - "Maintenance treatment" for acute leukaemia. PMID- 2877289 TI - Combined intra-abdominal and intrauterine pregnancies after gamete intrafallopian transfer. PMID- 2877291 TI - Impaired prostacyclin synthesis by vessel walls in Behcet's disease. PMID- 2877292 TI - Calcium and blood pressure. PMID- 2877293 TI - Intranuclear inclusions in marrow of hydropic fetus due to parvovirus infection. PMID- 2877294 TI - Chlamydia detection in extragenital specimens. PMID- 2877296 TI - Comparison of spatulas for cervical smears. PMID- 2877295 TI - Fatal neonatal varicella infection. PMID- 2877297 TI - Growth factors and malignancy. PMID- 2877298 TI - Adult coeliac disease presenting with symptoms of worsening asthma. PMID- 2877299 TI - Airway obstruction and heroin inhalation. PMID- 2877300 TI - Isolation of human immunodeficiency virus and serum neutralising antibody. PMID- 2877301 TI - Chymopapain. PMID- 2877302 TI - Envelope perturbation and AIDS. PMID- 2877303 TI - Incidence of gonorrhoea and fear of AIDS. PMID- 2877304 TI - Ophthalmomanometry-Doppler and ocular pneumoplethysmography. PMID- 2877305 TI - Informed consent. PMID- 2877306 TI - Medical care and military occupation. PMID- 2877307 TI - Deferred therapy in prostatic cancer. PMID- 2877308 TI - Early relapses after plasma exchange in acute inflammatory polyradiculoneuropathy. PMID- 2877309 TI - Somatostatin and heat sensitivity in multiple sclerosis. PMID- 2877310 TI - Sex, iron, and heart disease. PMID- 2877311 TI - Fatal liver cirrhosis associated with long-term arterial infusion of floxuridine. PMID- 2877312 TI - Bacterial arthritis. PMID- 2877313 TI - Parkinson's disease and pesticides. PMID- 2877314 TI - Adjuvant chemotherapy combined with tamoxifen in postmenopausal patients with stage II breast cancer. PMID- 2877315 TI - Verapamil, low-sodium regimens, and blood pressure. PMID- 2877316 TI - Serological diagnosis of staphylococcal bacteraemia. PMID- 2877317 TI - Teicoplanin-resistant coagulase-negative staphylococcus. PMID- 2877318 TI - Examining the parents of children with tuberous sclerosis. PMID- 2877319 TI - Enteric-coated prednisolone in cystic fibrosis. PMID- 2877320 TI - Peroxisomal alanine:glyoxylate aminotransferase and prenatal diagnosis of primary hyperoxaluria type 1. PMID- 2877321 TI - Serum cholesterol, blood pressure, and mortality. PMID- 2877322 TI - A sudden urgency about AIDS. PMID- 2877323 TI - Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. AB - Ten patients with end-stage renal failure and anaemia (mean haemoglobin 6.1 g/dl, range 4.6-8.8 g/dl) on thrice-weekly haemodialysis were treated with human erythropoietin derived from recombinant DNA (rHuEPO). This was given as an intravenous bolus after each dialysis in rising doses within the range 3-192 IU/kg. All patients showed increases in reticulocyte numbers and haemoglobin concentration and after the first week of treatment none of the four previously transfusion-dependent patients needed further transfusions. In nine patients treated for 12 weeks haemoglobin rose to a mean of 10.3 g/dl, range 9.5 to 12.8 g/dl. Thereafter the dose of erythropoietin was adjusted to avoid a further rise in haemoglobin. During treatment one patient had an episode of hypertensive encephalopathy and two had clotting in their arteriovenous fistulas (complete in one). rHuEPO is an effective treatment for the anaemia of end-stage renal failure but longer-term observations are needed on the consequences of increasing the haematocrit. PMID- 2877324 TI - Effect of duodenal ulcer surgery and enterogastric reflux on Campylobacter pyloridis. AB - To assess the effect of duodenal ulcer surgery on Campylobacter pyloridis gastric biopsies were done and fasting bile acid concentrations in gastric aspirates were measured in 35 patients with active duodenal ulceration and 54 who had undergone surgery at some time. Biopsy specimens were assessed blind for the presence of C pyloridis and scored for severity of reflux gastritis by the use of a histological grading system. Among patients who had undergone highly selective vagotomy the proportion who were C pyloridis-positive was similar to that in the unoperated group, but among those who had undergone Billroth I partial gastrectomy, Billroth II partial gastrectomy, or truncal vagotomy and gastroenterostomy it was significantly lower (p less than 0.001). The absence of C pyloridis correlated strongly (p less than 0.001) with high reflux scores and increased bile acid concentrations in the stomach. Reflux scores and bile acid concentrations were significantly higher (p less than 0.01) after Billroth I and Billroth II partial gastrectomies and truncal vagotomy and gastroenterostomy than in the active duodenal ulcer or highly selective vagotomy groups. There was a highly significant correlation (p less than 0.001) between reflux scores and bile acid concentrations. These results suggest that reflux may disrupt mucus and thus cause the death of campylobacters that live beneath it. They also suggest that reflux may produce a reflux-specific gastritis. Highly selective vagotomy may protect against these changes in the gastric mucosa. PMID- 2877325 TI - Diphtheria vaccine for adults. AB - A low dose (1.5 Lf) diphtheria vaccine for use in adults was given to 310 university student volunteers whose diphtheria antitoxin titres were less than 0.1 IU per ml. The incidence of adverse reactions was low. Postimmunisation blood samples taken from 134 of the students showed that in susceptible vaccinees the vaccine induced titres of antitoxin were consistent with protection and that it boosted the titres of those whose immunity was low. PMID- 2877326 TI - HLA and tropical sprue. AB - In 27 Puerto Rican patients with tropical sprue proven by intestinal biopsy and clinical response to folic acid, HLA type was determined with a microcytotoxicity assay. 25 of these patients had at least one antigen of the Aw-19 series (p = 10( 10)). The strongest association was with Aw-31, for which the relative risk was 10.6 (p = 1.2 X 10(-6)). The absence of a B-locus or haplotype effect suggests a marker association only, rather than an immune association. PMID- 2877327 TI - Effect of controlled axial micromovement on healing of tibial fractures. AB - The preliminary results are presented from a study in which 85 serious tibial fractures were treated with external skeletal fixation. In group I patients were treated with highly rigid fixation. In group II the same fixation was used but axial micromovement was applied across the fracture site for 30 min per day, starting 1-3 weeks after injury and continuing until partial weight-bearing, which leads to self-induced movement. The overall mean time to independent weight bearing was longer in group I than group II (p = 0.02); delayed union occurred in more group I patients. Objective measurement of fracture stiffness was made by means of strain gauges placed on the fixation frame for 49 fractures treated consecutively. The time to reach stiffness levels equivalent to clinical union was significantly longer in group I than in group II. The fractures in the treatment groups were of comparable severity. It seems that the fracture healing process is susceptible to small changes in mechanical environment. PMID- 2877329 TI - Preventive screening for fragile X syndrome. PMID- 2877328 TI - HLA-associated susceptibility to acquired immunodeficiency syndrome in Italian patients with human-immunodeficiency-virus infection. AB - To investigate the contribution of genetic susceptibility to infection with human immunodeficiency virus, 50 subjects with lymphadenopathy syndrome (LAS) and 7 subjects with acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma were typed for HLA A, B, C, and DR antigens. The frequency of B35 was significantly higher in LAS patients who progressed to AIDS than in those who did not or in healthy controls. The association between DR5 and AIDS/Kaposi's sarcoma was also confirmed in these patients. PMID- 2877330 TI - Cardiotoxicity of local anaesthetic drugs. PMID- 2877331 TI - Yohimbine: time for resurrection? PMID- 2877333 TI - Is there a role for the hinged-knee prosthesis? PMID- 2877332 TI - Late sequelae of poliomyelitis. PMID- 2877334 TI - Uterine fibroids: medical treatment or surgery? PMID- 2877335 TI - No evidence for increased risk of Lassa fever infection in hospital staff. AB - A prospective serological study was undertaken in hospital personnel who care for Lassa fever (LF) patients in an endemic region of Sierra Leone, West Africa. Among personnel from three hospitals where barrier nursing is practised, antibody prevalence and seroconversion by age and sex were consistently equal to or lower than those of persons in nearby village populations. No group among hospital personnel evaluated by age, sex, contact, or occupational exposure was at higher risk than another. Hospital staff in Sierra Leone who care for LF patients using simple barrier nursing methods have no higher risk of infection than the local population. These findings support the proposal that patients with LF in non endemic countries need not be confined to isolators. PMID- 2877336 TI - Sleep after transmeridian flights. AB - Nocturnal sleep and daytime sleep latencies, recorded electroencephalographically after westward and eastward flights across the North Atlantic involving time zone shifts of 5 h, were influenced by the time of the flight and by subsequent displacement of the rest period. After the westward flight there was sleep disturbance during the latter part of the first night. However, there was persistent disturbance of sleep after the eastward flight. A rapidly eliminated hypnotic may be useful for the first night or two after a westward flight and for a few nights after an overnight eastward flight. PMID- 2877338 TI - Perinatal mortality--a suitable index of health worldwide? PMID- 2877337 TI - Would screening prevent the international spread of AIDS? PMID- 2877339 TI - Acquired coagulation defect in resin-treated hypercholesterolaemia. PMID- 2877340 TI - Colestipol plus fenofibrate versus synvinolin in familial hypercholesterolaemia. PMID- 2877341 TI - Rapid reduction of uterine myomas after short-term treatment with microencapsulated D-Trp6-LHRH. PMID- 2877342 TI - Fatal Coxsackie B meningoencephalitis diagnosed by serology and in-situ nucleic acid hybridisation. PMID- 2877343 TI - Antibodies to HTLV-IV associated with chronic, fatal illness resembling "slim" disease. PMID- 2877344 TI - Components of saliva inactivate human immunodeficiency virus. PMID- 2877345 TI - Serum neopterin and beta 2-microglobulin in anti-HIV positive blood donors. PMID- 2877346 TI - Who will get AIDS? PMID- 2877347 TI - Arterial calcification and tourniquets. PMID- 2877348 TI - Useless drugs? PMID- 2877349 TI - Enalapril-induced cough. PMID- 2877350 TI - Torsades de pointe with prenylamine. PMID- 2877351 TI - Pseudomonal toxic shock syndrome. PMID- 2877352 TI - Cephalosporins as risk factor for enterococcal nosocomial urinary tract infections. PMID- 2877353 TI - Dechloroethylation of ifosfamide and neurotoxicity. PMID- 2877354 TI - Bone-marrow transplantation and radiation accidents. PMID- 2877355 TI - Thyroid radiation dose in Britain arising from the Chernobyl accident. PMID- 2877356 TI - Ileal predilection of graft-versus-host disease. PMID- 2877357 TI - Procollagen-III-peptide and hyperthyroidism. PMID- 2877358 TI - Informed consent. PMID- 2877359 TI - Fetal alcohol syndrome is now leading cause of mental retardation. PMID- 2877360 TI - Pain and the mother-child interaction. PMID- 2877361 TI - Acute transverse myelitis as presenting neurological feature of Lyme disease. PMID- 2877362 TI - Spirochaetes and Lyme disease. PMID- 2877364 TI - Catatonia. PMID- 2877363 TI - 99mTc-hexamethylpropyleneamine oxime scans to confirm brain death. PMID- 2877365 TI - Borderline personality disorders. PMID- 2877366 TI - Anaphylactoid reaction in platelet-pheresis donor with IgE antibodies to ethylene oxide. PMID- 2877368 TI - Dupuytren's contracture. PMID- 2877367 TI - Does mild atypia on a cervical smear warrant further investigation? PMID- 2877369 TI - Which spatula for cervical cytology? PMID- 2877370 TI - Parvovirus infection after renal transplant. PMID- 2877371 TI - Benzalkonium chloride and bronchoconstriction. PMID- 2877372 TI - Transplantation in fulminant hepatic failure. PMID- 2877373 TI - [Sports medicine and life insurance medicine]. PMID- 2877374 TI - [Surgical therapy of Crohn disease]. PMID- 2877375 TI - [Regional chemotherapy in liver metastases and prognosis]. PMID- 2877376 TI - [Immunotherapy of malignant growth]. PMID- 2877377 TI - [Human pathogenic papillomaviruses and cancer]. PMID- 2877378 TI - [Cancer of Vater's papilla. Clinical aspects, morphology and prognosis. Ulm collection of rare tumors (VIII.)]. PMID- 2877379 TI - [Insurability following cancer]. PMID- 2877380 TI - Spectral and inhibitory interactions of (+/-)-3,4-methylenedioxyamphetamine (MDA) and (+/-)-3,4-methylenedioxymethamphetamine (MDMA) with rat hepatic microsomes. AB - Incubation of racemic methylenedioxyamphetamine (MDA) or methylenedioxymethamphetamine (MDMA) with rat hepatic microsomes, in the presence of NADPH, generated a spectrally observed inhibitory complex with cytochrome P 450. The complex inhibited product formation from MDA and MDMA as well as other P 450 dependent reactions such as benzphetamine demethylation and CO binding. In the absence of NADPH, MDMA and MDA generated type I and type IIa difference spectra, respectively, suggesting differences in their binding to the enzyme active site. The N-demethylation of MDMA was partially inhibited by methimazole suggesting involvement of the hepatic flavin-containing monooxygenase. PMID- 2877382 TI - Prolyl-leucyl-glycinamide (PLG): inhibition of offensive aggression in mice. AB - The effects on offensive aggression of the endogenous peptide-leucyl-glycinamide (PLG, MIF-1) and the exogenous opiate antagonist, naloxone, were examined in male mice. PLG (0.01-10 mg/Kg) reduced, in a dose-dependent manner, the incidence and intensity of offensive aggression in dominant resident mice. PLG was more potent than naloxone (1.0 mg/Kg). In a number of cases, PLG completely eliminated the display of offensive aggression towards intruder mice. These results raise the possibility that PLG may function as an "anti-aggressive" peptide whose actions may include antagonistic and/or modulatory influences on both opioid and non opioid systems. PMID- 2877381 TI - Evaluation of studies on platelet alpha 2 adrenoreceptors in depressive illness. AB - Discrepant results have been reported from at least ten laboratories regarding the status of platelet alpha 2 adrenoreceptors in depressed patients. Using a statistical test to combine those studies which utilized radioligand binding techniques, we find the overall data support an elevation in density of platelet alpha 2 adrenoreceptors from drug-free depressed patients (p less than 0.05) and suggest a normalization to lower binding values following antidepressant drug treatment (0.05 less than p less than 0.10). However, these positive results are attributable to highly significant findings by only three laboratories. Much of the discrepancy may be attributable to numerous methodological variables which distinguish the studies. Foremost amongst these variables are the use of different platelet size populations, the use of different medium, and the choice of radioactive ligand and competitor (non-radioactive ligand) in the assay. We present a rationale for the proper choice of each methodological condition used in the clinical assessment of platelet alpha 2 adrenoreceptor status, hoping that improved experimental designs will resolve the current controversy. PMID- 2877383 TI - Steroids in chronic B-hepatitis. A randomized, double-blind, multinational trial on the effect of low-dose, long-term treatment on survival. A trial group of the European Association for the Study of the Liver. AB - The effect of long-term, low-dose prednisolone treatment on the survival of patients with chronic B-hepatitis was studied in a randomized, double-blind multicentre trial. Twenty-two centres from 11 European countries included 99 patients in the trial. Survival analysis showed 2.9 (95% confidence limit 0.9-9) times greater mortality in the prednisolone than in the placebo group (P = 0.07). In a Cox regression analysis, correcting for the influence of other prognostic factors, the detrimental effect of prednisolone treatment was unchanged. Mortality increased significantly with age, and patients without piece-meal necrosis had 7 times higher mortality than those with this change on entry to the trial. It is concluded that long-term, low-dose prednisolone treatment is very unlikely to be beneficial, and should be considered harmful in chronic B hepatitis, particularly in the most severe and advanced cases. PMID- 2877384 TI - [Consequences of foot frostbite during alcoholic intoxication]. PMID- 2877385 TI - [Blood pressure regulation by the interaction of the central serotonergic system with other neurotransmitters]. PMID- 2877386 TI - Metoprolol or hydrochlorothiazide in patients with hypertension aged 60-75 years. With special reference to assessment of compliance. Hunter Hypertension Research Group. AB - The blood pressure of patients with hypertension who were aged between 60 and 75 years responded equally well to treatment with metoprolol (100 mg a day) or hydrochlorothiazide (25 mg a day) in a double-blind study which employed random allocation to two parallel groups. Drug-related variables other than blood pressure were used as markers of compliance. The resting heart rate alone discriminated substantially between the groups, but the discrimination was not increased by the inclusion of plasma potassium or plasma urate levels in the calculation. For the assessment of compliance, we suggest that greater use could be made of objective variables that are altered by drug treatment and are unrelated to the primary variable of interest in the study. PMID- 2877387 TI - International milestones 1985. PMID- 2877388 TI - [Nodose polyarteritis of the spleen with Bence-Jones kappa type paraproteinuria]. PMID- 2877389 TI - St. Louis encephalitis--Baytown and Houston, Texas. PMID- 2877390 TI - Phenylarsine oxide inhibits agonist-induced changes in photolabeling but not agonist-induced desensitization of the beta-adrenergic receptor. AB - In the human lymphocyte, desensitization of the beta-adrenergic receptor adenylate cyclase complex is associated with sequestration of the receptor as well as a change in photolabeling of beta-receptor proteins. Thus, desensitization of the lymphocyte beta-adrenergic receptor-adenylate cyclase system is associated with a selective reduction in the photoaffinity labeling of an Mr approximately equal to 55,000 beta-adrenergic receptor-binding site as compared to an Mr approximately equal to 68,000 beta-adrenergic receptor-binding moiety. In order to examine the relationship between sequestration and reduction in labeling of the Mr approximately equal to 55,000 peptide, we have studied the effect of phenylarsine oxide (an inhibitor of beta-receptor sequestration in astrocytoma cells) on agonist-induced desensitization of the beta-adrenergic receptor-adenylate cyclase system in circulating lymphocytes. Incubation of cells with phenylarsine oxide prior to exposure to agonists did not block the consequent reduction in isoproterenol-stimulated adenylate cyclase activity. However, sequestration of the receptor, as assessed by a decrease in accessibility of beta-adrenergic receptors on intact cells to hydrophilic receptor ligands, is blocked by phenylarsine oxide. Thus, the agonist-induced reduction in binding of the hydrophilic beta-adrenergic receptor ligand CGP-12177 was blocked by phenylarsine oxide (without phenylarsine oxide, 57 +/- 6% of control, with phenylarsine oxide, 97 +/- 3% of control). Photolabeling studies with [125I]iodocyanopindolol diazirine revealed that phenylarsine oxide pretreatment also blocked the selective loss in labeling of the Mr approximately equal to 55,000 beta-adrenergic receptor protein. These data suggest that agonist induced alterations in the photolabeling pattern of the lymphocyte beta adrenergic receptor that occur with desensitization closely parallel the apparent sequestration of beta-adrenergic receptors but can be dissociated from the initial desensitization phenomenon. PMID- 2877391 TI - Phosphorylation of tyrosine hydroxylase on at least three sites in rat pheochromocytoma PC12 cells treated with 56 mM K+: determination of the sites on tyrosine hydroxylase phosphorylated by cyclic AMP-dependent and calcium/calmodulin-dependent protein kinases. AB - Incubation of rat pheochromocytoma PC12 cells with the calcium ionophore, A23187 (10(-5) M), 56 mM K+, or dibutyryl cAMP (2 mM) is associated with increased activity and enhanced phosphorylation of tyrosine hydroxylase in the cells. Both the activation and the increased phosphorylation of tyrosine hydroxylase produced by A23187 and 56 mM K+ are dependent on the presence of extracellular calcium, whereas similar effects produced by dibutyryl cAMP are independent of calcium. The effects of 56 mM K+ plus dibutyryl cAMP or A23187 plus dibutyryl cAMP on the activation and phosphorylation of tyrosine hydroxylase are additive. In contrast, the effects of 56 mM K+ plus A23187 on either the activation or the phosphorylation of the enzyme are not additive. Following stimulation of intact PC12 cells with 32Pi, in order to label ATP stores, and tryptic digestion of the phosphorylated enzyme, separation of the tryptic phosphopeptides by high pressure liquid chromatography yields four distinct 32P-peptide peaks. Incubation of the cells in the presence of either 56 mM K+ or A23187 is associated with increased 32Pi incorporation into three peptides whereas, in the presence of dibutyryl cAMP, increased 32Pi incorporation is observed in only one of these peptides. When tyrosine hydroxylase purified from rat pheochromocytoma tumor is incubated in vitro with [gamma-32P]ATP and either cAMP-dependent or calcium/calmodulin dependent protein kinase under appropriate conditions, increased phosphorylation of tyrosine hydroxylase is observed. However, even though in vitro phosphorylation by cAMP-dependent protein kinase is associated with activation of tyrosine hydroxylase, in vitro phosphorylation by calcium/calmodulin-dependent protein kinase does not lead to activation of the enzyme. Tryptic digestion of tyrosine hydroxylase phosphorylated by calcium/calmodulin-dependent protein kinase yields three distinct 32P-peptide peaks, which are identical to those phosphorylated by treatment of intact PC12 cells with either high K+ or A23187. In contrast, cAMP-dependent protein kinase phosphorylates only one peptide, which is identical to that phosphorylated by treatment of the intact cells with dibutyryl cAMP. These results indicate that tyrosine hydroxylase is activated and phosphorylated at multiple sites in PC12 cells exposed to 56 mM K+ or A23187. The results suggests that the in situ phosphorylation of these sites is catalyzed by calcium/calmodulin-dependent protein kinase; however, phosphorylation by this protein kinase is not sufficient to activate the enzyme. PMID- 2877392 TI - Induction of mRNA for tyrosine hydroxylase by cyclic AMP and glucocorticoids in a rat pheochromocytoma cell line: evidence for the regulation of tyrosine hydroxylase synthesis by multiple mechanisms in cells exposed to elevated levels of both inducing agents. AB - When rat pheochromocytoma PC18 cells are exposed to the cyclic AMP analog, 8 bromocyclic AMP, and/or the synthetic glucocorticoid, dexamethasone, there is a marked increase in the level of a single RNA species that hybridizes to the recombinant plasmid pTH.4, which contains sequences complementary to the RNA coding for tyrosine hydroxylase. This RNA species is 1800-1900 nucleotides in length and is presumably identical to an RNA species of similar size, isolated from rat pheochromocytoma PC8b cells and shown to code for tyrosine hydroxylase. Using RNA dot hybridization to quantitate the relative level of this tyrosine mRNA species, time course studies show that this mRNA increases relatively rapidly in PC18 cells treated with either 8-bromocyclic AMP or dexamethasone. A new steady state level of tyrosine hydroxylase mRNA is achieved after 6 hr or 12 24 hr of treatment with either 8-bromocyclic AMP or dexamethasone, respectively. The changes in the level of the mRNA slightly precede the changes in the rate of synthesis of tyrosine hydroxylase in cells treated with these inducing agents. After 24 hr of treatment with either 8-bromocyclic AMP or dexamethasone, the increases in the level of tyrosine hydroxylase mRNA are identical to the increases in the rate of synthesis of the enzyme in the cells. In cells treated simultaneously with both 8-bromocyclic AMP and dexamethasone, the increases in the enzyme level and rate of synthesis of tyrosine hydroxylase are approximately equal to the sum of the increases in these parameters observed in cells treated with either inducing agent alone. In contrast, there is not an additive increase in the level of tyrosine hydroxylase mRNA in cells treated with both inducing agents. This lack of an additive increase in mRNA for tyrosine hydroxylase is observed in total cellular RNA samples or in cytoplasmic RNA samples. Our results suggest that in cells exposed to elevated levels of either cyclic AMP or glucocorticoids, tyrosine hydroxylase is induced by a mechanism which increases the level of its mRNA, resulting in an increased rate of synthesis of the enzyme. However, in cells exposed to elevated levels of both cyclic AMP and dexamethasone, tyrosine hydroxylase enzyme levels are regulated by multiple mechanisms, one of which regulates the rate of synthesis of the enzyme without affecting the level of its mRNA. PMID- 2877393 TI - The integrated approach to the management of pain. PMID- 2877394 TI - Mechanism and relevance of glutathione mutagenicity. AB - The ubiquitous tripeptide glutathione (GSH) has previously been shown to be mutagenic to Salmonella typhimurium TA100 when incubated with kidney subcellular fractions at physiological concentrations (Glatt et al., 1983). Here we report that the mutagenic effect of GSH can be inhibited by the use of the gamma glutamyl-transpeptidase (gamma-GT) inhibitor anthglutin and by the metal chelators bathocuproine, EDTA and diethyldithiocarbamate. As the chelating agents did not inhibit gamma-GT activity this suggested that the mechanism underlying the mutagenic effect of GSH was at least a two-step process, dependent upon the cleavage of GSH by gamma-GT and the presence of either free transition metals or those contained in enzymes such as glutathione oxidase. As gamma-GT is located on the outer surface of kidney tubule cells and is therefore exposed to relatively low concentrations of GSH, and the precise physiological control of levels of transition metals, this mechanism is unlikely to occur in vivo. PMID- 2877395 TI - Modulation of amino acid and 2-oxo acid pools in Trichomonas vaginalis by aspartate aminotransferase inhibitors. AB - The amino acid pool sizes of Trichomonas vaginalis are reported. Alanine, glutamic acid, proline and leucine account for 72% of the measured amino acids. Growth of T. vaginalis was unaffected by gostatin, an irreversible inhibitor of aspartate aminotransferase, when the enzyme activity within the cell had been completely inhibited and a specific elevation of the aspartate pool had occurred. In media lacking aspartate and glutamate, the amino acid substrates of the aspartate aminotransferase reaction, gostatin caused a larger increase in the aspartate pool. During incubation of cells with or without gostatin, aspartate and glutamate were produced in the medium, presumably by proteolysis of medium proteins. Hence any requirement for the aspartate aminotransferase reaction might have been bypassed. Glutamate-gamma-hydroxamate and aminooxyacetate inhibited growth of T. vaginalis but caused large changes in the pool-sizes of aspartate, glutamate, pyruvate plus oxaloacetate and 2-oxoglutarate, suggesting a more general interference with amino acid metabolism. PMID- 2877396 TI - Huntington's disease. Pathogenesis and management. PMID- 2877397 TI - Effects of postoperative mediastinal radiation on completely resected stage II and stage III epidermoid cancer of the lung. AB - We randomly assigned 230 patients with resected Stage II or III epidermoid (squamous-cell) lung cancer to receive postoperative adjuvant radiotherapy or no adjuvant treatment. Careful intraoperative staging had been performed in all patients. Before randomization, patients were stratified according to stage, weight loss, age, and institution. Prognostic variables, such as stage, weight loss, age, nodal-disease status, and tumor status, were equally distributed between the two groups. The mean time from randomization to analysis was 3.5 years among the 210 eligible patients. There was no evidence that radiotherapy improved survival, and although recurrence rates appeared to be somewhat reduced among patients assigned to radiotherapy, these decreases were not statistically significant. However, radiotherapy did produce a striking and significant reduction in recurrences to the ipsilateral lung and mediastinum. Moreover, overall recurrence rates were reduced by radiotherapy in patients with N2 disease (P less than 0.05), although even this subgroup had no evidence of improved survival. We conclude that radiotherapy can reduce local recurrences after resection of epidermoid carcinoma of the lung, but that it does not increase survival rates. PMID- 2877398 TI - A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. AB - The genomes of various tumour cells contain mutant oncogenes that act dominantly, in that their effects can be observed when they are introduced into non-malignant cells. There is evidence for another class of oncogenes, in which tumour predisposing mutations are recessive to wild-type alleles. Retinoblastoma is a prototype biological model for the study of such recessive oncogenes. This malignant tumour, which arises in the eyes of children, can be explained as the result of two distinct genetic changes, each causing loss of function of one of the two homologous copies at a single genetic locus, Rb, assigned to the q14 band of human chromosome 13. Mutations affecting this locus may be inherited from a parent, may arise during gametogenesis or may occur somatically. Those who inherit a mutant allele at this locus have a high incidence of non-ocular, second tumours, almost half of which are osteosarcomas believed to be caused by the same mutation. Here we describe the isolation of a complementary DNA segment that detects a chromosomal segment having the properties of the gene at this locus. The gene is expressed in many tumour types, but no RNA transcript has been found in retinoblastomas and osteosarcomas. The cDNA fragment detects a locus spanning at least 70 kilobases (kb) in human chromosome band 13q14, all or part of which is frequently deleted in retinoblastomas and osteosarcomas. PMID- 2877399 TI - The effect of the dopamine agonist pergolide on tyrosine hydroxylase activity in rat striatal and limbic miniprisms in vitro: a model for the dopamine autoreceptor? AB - A method for the assay of tyrosine hydroxylase activity in rat striatal and limbic (nucleus accumbens + olfactory tubercle) brain miniprisms is described. The dopamine agonists apomorphine (1 mumol/l) and pergolide (0.01-100 mumol/l) inhibited the tyrosine hydroxylase activity in both regions. The inhibition produced by 1 mumol/l pergolide was antagonised partially in striatal miniprisms and completely in limbic miniprisms by 1 mumol/l haloperidol. The dopamine D2 selective antagonist raclopride, at concentrations up to 300 nmol/l, did not antagonise the inhibition produced by pergolide in striatal miniprisms, but appeared partially to antagonise the inhibition in limbic miniprisms. It is concluded that whilst pergolide potently inhibits tyrosine hydroxylase activity in striatal and limbic miniprisms, the inhibition is of doubtful value as a predictive model of dopamine autoreceptor function in striatal miniprisms, but may be useful when limbic miniprisms are used. PMID- 2877402 TI - [Antihistaminics (H1 receptor blocking agents)]. PMID- 2877400 TI - Possible involvement of presynaptic alpha 1-adrenoceptors in the effects of idazoxan and prazosin on 3H-noradrenaline release from tail arteries of SHR. AB - The effects of several alpha-adrenoceptor antagonists have been examined on tritium release elicited by electrical stimulation from isolated perfused SHR tail artery preparations prelabelled with 3H-noradrenaline (3H-NA). Phentolamine and yohimbine potently facilitated the stimulation evoked release of tritium at low frequencies of stimulation, but the alpha 2-adrenoceptor antagonist idazoxan was only weakly active at 1 mumol/l, despite antagonising the clonidine-evoked inhibition of 3H-release at a lower concentration of 0.1 mumol/l. The alpha 1 adrenoceptor antagonists prazosin and corynanthine also increased stimulation evoked tritium release in this preparation, suggesting the presence of prejunctional alpha 1-adrenoceptors. Furthermore, the alpha 1-adrenoceptor agonist methoxamine (3 mumol/l) caused a significant inhibition of tritium-evoked release, an effect which was blocked by prazosin (10 nmol/l). When alpha 1 adrenoceptors were blocked in the presence of prazosin, idazoxan (0.1 mumol/l) produced a significant facilitatory effect on the electrically-evoked release of 3H-transmitter. On the other hand, when alpha 2-adrenoceptors were blocked in the presence of yohimbine, exposure to idazoxan (0.1 mumol/l) reduced significantly the stimulation-evoked release of tritium elicited by electrical stimulation. The results indicate that in the SHR tail arteries, idazoxan has a partial agonist inhibitory activity on transmitter release, which can mask the facilitatory effects due to blockade of presynaptic alpha 2-adrenoceptors. The inhibitory effects of idazoxan appear to involve presynaptic alpha 1-adrenoceptors, which when stimulated, reduce 3H-NA release in SHR tail arteries. PMID- 2877403 TI - [Overdoses of flunitrazepam and various other benzodiazepines; experiences of the National Poisoning Information Center]. PMID- 2877401 TI - Effects of noradrenaline and somatostatin on basal and stimulated mucosal ion transport in the guinea-pig small intestine. AB - Noradrenaline (NA) and somatostatin (SOM) stimulate intestinal water and ion absorption and are found in mucosal nerve fibres and nerve terminals in submucous ganglia of the guinea-pig small intestine. As the main projection of submucous neurons is to the mucosa, NA and SOM might alter mucosal transport either by a direct effect on the epithelium or indirectly, by affecting submucous neurons. In this study these two possible sites of action of NA and SOM have been investigated in mucosa-submucosa preparations of guinea-pig ileum. In addition, the actions of NA and SOM on the secretory responses caused by stimulation of different populations of submucous neurons have been studied. The stimulants of secretion used were a nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium (DMPP, 10(-5) M), 5-hydroxytryptamine (5-HT, 10(-7) M) and electrical field stimulation (EFS), which activate cholinergic, noncholinergic and mixed populations of submucous secretomotor neurons, respectively. Segments of intestine were dissected free of external muscle and myenteric plexus and mounted in Ussing chambers. Short-circuit current (Isc) was measured as an indication of net active ion transport across the tissue. NA (greater than or equal to 10(-8) M) and SOM (greater than 10(-10) M) each caused a decrease in Isc, indicating a net increase in ion absorption. The NA response was abolished and the magnitude of the SOM response was reduced to 20% by tetrodotoxin (10(-7) M). DMPP, 5-HT and EFS each stimulated nerves that increased Isc and each of these responses was significantly diminished by NA and SOM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877404 TI - [Effect of cholinergic compounds on spontaneous quantal mediator release at the neuromuscular synapse of the frog]. AB - The action of cholinergic drugs on spontaneous quantal transmitter release has been investigated in the frog sartorius muscle. Acetylcholine and carbacholine decreased the miniature end-plate potential frequency. These presynaptic effects had no dependence on the potassium concentration in the bath solution. Nicotinic agonists--nicotine, tetramethylammonium and suberyldicholine had a similar effect, while muscarinic agents--methylfurmetide, oxotremorine and F-2268 (L- and D-stereoisomers) did not affect the transmitter release. The presynaptic effects of carbacholine and acetylcholine were abolished neither by atropine nor by d tubocurarine and bensohexonium. It is suggested that there are nicotinic receptors on the frog motor nerve terminals that modify spontaneous quantal transmitter release and differ pharmacologically from nicotinic end-plate, ganglionic and presynaptic receptors of higher vertebrates. PMID- 2877405 TI - [Neurological complications after vaccination against rabies as exemplified by 4 cases from Poznan province]. AB - The author reports 4 cases of neurological complications following vaccination with cerebral-type lyophilized vaccine. The cases were observed in the Province of Poznan in the period from January to April 1984, and the patients were men aged 41 to 60 years with various clinical syndromes: Landry's ascending paralysis, polyradiculoneuritis, polyneuritis and encephalopolyradiculoneuritis. The high frequency of these complications (about 3%) might have been due to the high susceptibility of the vaccinated population, or to technical errors in the production of the vaccine leading to obtaining of a vaccine bath with a high immunoallergogenicity which could trigger off the complication in persons with individual predisposition. PMID- 2877406 TI - Progress in syringomyelia. AB - Syringomyelia management is showing some progressive improvements following surgical methods of investigation and treatment. Investigation of simultaneous pressure changes in the cerebrospinal fluid pathways has illustrated the importance of craniospinal pressure dissociation in impacting the cerebellar and medullary tissues in the foramen magnum in hindbrain related syringomyelia. Such pressure differences may be referred to as 'suck' and similar changes are to be found in non-hindbrain related forms of syringomyelia such as those associated with spinal arachnoiditis. When cavities have formed then impulsive movements may occur with them and enlargement of the cavities may be continued by sloshing of the fluid within them. Investigations have been improved following the widespread use of water soluble contrast media and CT scanning with reconstructions after myelography. A definite relationship between birth injury and hindbrain related syringomyelia has been established especially with cases showing arachnoiditis. The nature of the relationship to hindbrain hernia and basilar invagination remains unclear. Magnetic resonance imaging holds great promise particularly in showing hindbrain deformation in new-born babies, showing whether or not a communication commonly exists between the fourth ventricle and the cavities within the spinal cord in early childhood and also in outlining the changes in the spinal cord in the presence of acute traumatic paraplegia. Treatment still relies upon valved ventricular to extrathecal shunts for hydrocephalus, cranio vertebral decompression to prevent suck and drainage of the syrinx in appropriate cases. Syrinx to extrathecal shunting may be preferred to shunts to the subarachnoid space. The peritoneum and the pleura are favoured sites and a valve is not necessary. The advances for the future may depend on earlier diagnosis and greater understanding of the mechanisms of pathogenesis in which MRI seems likely to play an increasingly important part. PMID- 2877407 TI - Influence of blood-brain barrier opening to proteins on development of post ischaemic brain injury. AB - The effect of the BBB opening to proteins on development of post-ischaemic brain injury was assessed in 32 cats subjected to one hour MCA occlusion. The CBF was measured by hydrogen clearance from electrodes inserted in the caudate and the cerebral cortex within the MCA territory. In 16 animals, a prevention of subsequent reactive hyperaemia was attempted by hypovolaemia, produced by withdrawal of blood just before the release of MCA occlusion. The hypovolaemia was successful in prevention of post-ischaemic hyperaemia in five out of eight cats sacrificed at 3 h and in six out of eight animals killed after 3 and 14 days. In cats sacrificed 3 h after release of MCA occlusion, ischaemic sites, associated with reactive hyperaemia, showed evidence of BBB breakdown to proteins and significantly more severe oedema than at the ischaemic sites without reactive hyperaemia, which otherwise failed to reveal leakage of EB tracer. In the cats sacrificed at 3 and 14 days, the ischaemic sites which showed reactive hyperaemia after release of MCA occlusion, revealed much more severe ischaemic brain tissue injury than was observed at the sites without reactive hyperaemia, which also did not show any EB leakage. The present study indicates that reactive hyperaemia, which follows release of major cerebral artery occlusion, may play a significant role in the breakdown of the BBB to proteins, and in increasing the severity of post-ischaemic oedema and of ischaemic brain tissue injury. PMID- 2877408 TI - Interactions of human fibroblast interferon with chemotherapeutic agents and radiation against human gliomas in nude mice. AB - The growth inhibitory effects of the combination of beta-interferon (beta-IFN) and conventional anticancer drugs such as adriamycin (ADM) and ACNU were evaluated in nude mice receiving subcutaneous transplants of human glioblastoma. Next, the anticancer and radiation sensitizing effects of beta-IFN on human glioblastoma was also evaluated in nude mice model. After three weeks of combined treatment, tumour reduction rates (treated/control values) were evaluated by the Battelle's method. In conclusion, the growth inhibitory effect of IFN was most enhanced when IFN was administered following radiotherapy. Furthermore, the combined effect was enhanced in proportion to the dose of radiation. PMID- 2877409 TI - Changes of somatosensory evoked potential accompanying ischaemia and hypoxia in cats. AB - Changes of evoked potential accompanying haemorrhagic hypotension and hypoxia were investigated on cats to evaluate the usefulness of SEP as a monitor in an intensive care unit (ICU), and the following results were obtained. Positive negative diphasic potential was elicited at posterior sigmoid gyrus(PSG) by contralateral superficial radial nerve stimulation. This potential was recorded at the restricted area of the posterior border of PSG and regarded as primary somatosensory evoked potential. In the initial stage of haemorrhagic hypotension, both positive and negative components of SEP occasionally increased in amplitude. In profound hypotension in which CBF fell to less than the critical level of 30 ml 100 g-1 min-1, the latency was retarded and the amplitude was decreased. At CBE less than 10 ml 100 g-1 min-1, SEP disappeared. Within the range of CBF between 10 and 30 ml 100 g-1 min, a close correlation was noted between CBF and SEP amplitude. Transient increase of SEP amplitude was also observed during hypoxia induced by inhalation of nitrogen gas. (3) In normal state SEP was decreased in amplitude by conditioning stimulation of the nucleus lateralis posterior (LP nucleus) of the thalamus. This might be explained by the fact that intracortical inhibitory interneurons were activated by stimulation of LP nucleus. After haemorrhagic hypotension and hypoxia, however, the inhibitory effect on SEP elicited by LP nucleus stimulation attenuated or disappeared. Because of the initial impairment of the inhibitory interneurons by ischaemia and hypoxia, the amplitude of SEP might increase transiently. In conclusion, the authors thought that SEP might be less useful than EEG in ICU, because of its insensible change to hypoxia and ischaemia. PMID- 2877410 TI - Positron emission tomographic evaluation of histological malignancy in gliomas using oxygen-15 and fluorine-18-fluorodeoxyglucose. AB - HEADTOME III, a high resolution PET, has been employed using 15O and 18F labelled pharmaceuticals to evaluate histological malignancy of gliomas preoperatively. PET study was applied on eighteen preoperative gliomas including two recurrent cases. Haemocirculatory and metabolic indices of regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), cerebral metabolic rates for oxygen (rCMRO2) and glucose (rCMRGI) were measured in the viable portion of the tumour, and the contralateral grey and white matter. In the tumour region, rCBF and rCBV were variable and unrelated to grades of tumour malignancy. rCMRO2 and rOEF values reduced significantly (p less than 0.01) relative to the contralateral brain tissue. The average rCMRGI values was 3.00 +/ 1.06 mg 100 ml-1 min-1 (mean +/- SD) for 7 low grade gliomas (grade II), and 5.91 +/- 3.61 mg 100 ml-1 min-1 for 11 high grade gliomas (grade III and IV). These results would support that anaerobic glycolysis increased in the metabolism of gliomas with malignancy. In comparison with normal volunteers, rCBF, rCMRO2, and rCMRGI values in the contralateral grey matter of gliomas were markedly reduced (p less than 0.01, p less than 0.05, p less than 0.01, respectively) possibly due in part to raised intracranial pressure and depressed cerebral functional activity, so that rOEF was increased to a level of approximately 0.5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877411 TI - Cerebral blood flow and metabolism in experimental hydrocephalus. AB - Cerebral blood flow and metabolism were studied in experimental hydrocephalus which was produced by intracisternal injection of kaolin in cats, rabbits and rats. Measurements were carried out in varied stages of hydrocephalus. Local cerebral blood flow (l-CBF) was measured by the hydrogen clearance method. Assessment of cerebral metabolism was made biochemically in the brain tissues of various regions, including water content, Na, K, lactate, pyruvate, lipids, ATP, cyclic AMP, catecholamines and monoamine metabolites. Blood flow studies were performed in the cerebral cortex, periventricular white matter, thalamus and midbrain reticular formation in hydrocephalic cats. In all of these regions, l CBF decreased to about half of the control in both acute and chronic stages of hydrocephalus. CO2 reactivity to CBF was impaired only in the acute stage, while autoregulation of CBF was preserved in the hydrocephalic brain. Water content of the brain tissue increased temporarily only within the periventricular white matter of hydrocephalic rabbits concomitant with increase in Na and decrease in K. Transient increase in the lactate and lactate/pyruvate ratios was also observed in the frontal lobe tissue. In hydrocephalic rats, decrease in phospholipids and cholesterol was observed parallel with the degree of ventricular dilatation. ATP and cyclic AMP decreased biphasically in both acute and chronic stages. On the other hand, increase in concentrations of norepinephrine, dopamine, homovanillic acid, and 5-hydroxyindoleacetic acid became evident in the chronic stage of hydrocephalus. From the above results, it is concluded that the hydrocephalic brain sustained considerable disturbance of metabolism in all modalities in association with decreased blood flow, which is sufficient to explain the clinical symptoms of hydrocephalus. PMID- 2877412 TI - Outcome of ruptured intra-cranial aneurysm treated by a deferred operation. Review of 345 consecutive cases treated over a period of 12 years. AB - This paper reports experience with 345 patients admitted to a neurosurgical department after an aneurysm rupture. At the time of admission, patients were separated into two groups: the patients unsuitable for planned surgery and called 'unoperable'; the patients planned for surgery and called 'operable patients' (328 patients). The general management attitude consisted of deferred surgery according to the clinical status of the patients and the risk of vasospasm and ischaemia. Of these, 18 died before the day of surgery, and are called 'operable and non-operated' patients. The cause of death was vasospasm and ischaemia in 10 cases and recurrence of haemorrhage in 8 cases. 310 patients were actually operated upon. Their final outcome was: good 70%, fair 9.6%, poor 7.7%, death 12.5%. This paper discusses the risk of SAH recurrence and the risk of vasospasm and ischaemia during the waiting time before surgery, in the attitude of deferred surgery which was elected in most cases of this series and compares the outcome with other published series. PMID- 2877413 TI - Chronic pain treatment with intravenous lidocaine. AB - In a few uncontrolled studies intravenous lidocaine has been used in the treatment of chronic pain. In a controlled study we used intravenous lidocaine in 18 patients with severe chronic pain states due to various but mainly neurological diseases. After the infusion of lidocaine 14 patients (78%) had significant pain relief ranging from 2 hours to 25 days. There was no significant effect of placebo infusion with isotonic saline. The mechanism of the pain relieving ability of intravenous lidocaine is unknown. PMID- 2877414 TI - Continuously infused 2-amino-7-phosphonoheptanoic acid antagonizes N-methyl-D aspartate-induced elevations of cyclic GMP in vivo in multiple brain areas and chemically-induced seizure activity. AB - The effects of the chronic intracerebroventricular (i.c.v.) infusion of the potent dicarboxylic amino acid antagonist, 2-amino-7-phosphonoheptanoic acid (APH), were examined in female rats as a prelude to the use of this compound in exploring the role of dicarboxylic amino acids in barbiturate dependence and withdrawal. Doses of APH ranging from 2.7 to 54 micrograms/day were examined for signs of toxicity. Weight loss, decreased water intake and locomotor impairment were found only with the largest dose. No significant changes in consumption of food or body temperature were observed with any dose. The chronic administration of the drug (27 micrograms/day) blocked the elevation of the content of cyclic guanosine monophosphate induced by N-methyl-D-aspartate (NMDA) in all regions of the brain examined. The chronically-administered drug also blocked wild running behavior induced by the intracerebroventricular administration of two different drugs n-methyl-D-aspartic acid and cyclohexylbarbiturate acid. However, APH was ineffective in suppressing convulsions induced by the ED50 dose of pentylenetetrazol given subcutaneously. PMID- 2877415 TI - Gastric acid secretory responses to cholinergic and histaminergic stimulation in chronic morphine-treated rats. AB - The effects of chronic morphine administration on cholinergic and histaminergic activities were evaluated in rats by observing their gastric acid secretory responses to secretagogues. The responses of in-vivo perfused stomachs to 2-deoxy D-glucose or pentagastrin, and of the isolated gastric mucosa to histamine or bethanechol, were not significantly different between naive and chronic morphine treated animals. It is suggested that the chronic morphine-treated rats exhibit normal cholinergic and histaminergic activities as well as receptor sensitivities to acetylcholine and histamine. PMID- 2877416 TI - The role of GABA and excitatory amino acids in the development of the leptazol induced epileptogenic EEG. AB - The developing epileptogenic electroencephalogram (EEG), seen during the slow intravenous infusion of leptazol, is sensitive to various anticonvulsant drugs, particularly those known to augment the function of gamma-aminobutyric acid (GABA), such as clonazepam and sodium valproate, which specifically prolong the earlier wave-like (pre-spiking) phases. Thus, whilst antagonism of GABA may be responsible for spiking, the early wave-like phases may be due to GABA released in the cortex as a feedback control to delay spiking. Intravenous infusion of the GABA antagonists, bicuculline and picrotoxin, produced a developing EEG with spiking the first abnormal feature noted and no wave-like phase, like that seen with leptazol. Cortical superfusion of GABA during the infusion of leptazol, enhanced kand prolonged the wave-like phase, whilst bicuculline reduced it. Cortical superfusion of leptazol, picrotoxin or larger concentrations of bicuculline produced spiking but no wave-like activity. When leptazol and GABA were superfused together they produced wave-like activity similar to that seen during infusions of leptazol. Of the excitatory amino acid antagonists, only those active at receptors for N-methyl-D-aspartate (NMDA) influenced the EEG changes induced by leptazol. It is suggested that leptazol produces waves in the EEG by stimulating subcortical pathways to release GABA in the cortex and that spiking occurs as the cortex is further stimulated by GABA antagonism and the release of excitatory amino acids. PMID- 2877418 TI - An N-methyl-D-aspartate (NMDA) receptor antagonist reduces bicuculline-induced depolarization shifts in neocortical explant cultures. AB - We investigated the actions of a specific N-methyl-D-aspartate (NMDA) antagonist, 2-amino-5-phosphonovaleric acid (2-APV), on bicuculline-induced epileptogenesis in organotypic explant cultures from neonatal rat neocortex. Explants were maintained in roller tubes for 3-5 weeks. The late, plateau phase of the intracellularly recorded paroxysmal depolarization shift was sensitive to both intracellularly injected hyperpolarizing currents and 2-APV, suggesting that this component is generated by a voltage-dependent, regenerative process that is mediated by activation of NMDA receptors. The results support the hypothesis that NMDA receptors play an important role in the generation of epileptiform activity by localized circuits of neocortical neurons. PMID- 2877417 TI - Effects of tiaspirone (BMY-13859) and a chemical congener (BMY-13980) on A9 and A10 dopamine neurons in the rat. AB - Two new potential antipsychotic drugs, BMY-13980 and BMY-13859 were compared for the ability to influence the electrophysiological activity of dopaminergic neurons in the substantia nigra zona compacta (A9 DA cells) and ventral tegmental area (A10 DA cells) in the brain of the rat. Both drugs reversed the rate suppressant effects of the DA agonist apomorphine on DA cells in A10 to a greater extent than DA cells in A9; BMY-13980 was particularly selective in this regard. These results indicate that both drugs may exert DA antagonist effects which are suggestive of antipsychotic potential. In other experiments, the effects of chronic (28 days) treatment with BMY-13980 and BMY-13859 on the neuronal activity of DA were evaluated. Both compounds caused a significant decrease in the number of spontaneously active DA neurons in A10 recorded per electrode track, an effect previously demonstrated to be associated with antipsychotic efficacy. The drug BMY-13859, but not BMY-13980, also significantly decreased the number of spontaneously active DA cells/track in A9, an effect which may predict the liability of potential antipsychotic drugs for causing extrapyramidal motor dysfunction, including tardive dyskinesia. Thus, these experiments indicate that both BMY-13980 and BMY-13859 exert effects which may predict potential antipsychotic efficacy in clinical trials and that BMY-13980 may be less likely to cause extrapyramidal side effects. PMID- 2877419 TI - Deprivation of REM sleep in the rat and the opioid peptides beta-endorphin and dynorphin. AB - Effects of 'rapid eye movement' sleep deprivation (REMd) on two opioid peptides, beta-endorphin and dynorphin, were studied in rats. Both peptides were measured by radioimmunoassay techniques. The level of beta-endorphin was estimated in the hypothalamus, in the anterior lobe of the pituitary and in the blood. The amount of dynorphin was estimated in the hypothalamus. REMd was induced for 72 h and achieved by two different methods, the platform technique and the pendulum technique. Three control groups were additionally run. As a consequence of REMd, an increase in beta-endorphin level was discovered in the blood plasma, while a small decrease was found in the hypothalamus. No changes could be detected for beta-endorphin levels in the pituitary or for hypothalamic dynorphin concentration. The deprivation effects are interpreted as belonging to a group of changes, all of which point to a small increase in tonic arousal as a result of REMd. PMID- 2877420 TI - Decreased somatostatin immunoreactivity but not neuropeptide Y immunoreactivity in cerebral cortex in senile dementia of Alzheimer type. AB - The content of two neuropeptides, somatostatin (SRIF) and neuropeptide Y (NPY) has been determined in two cerebral cortical areas of Alzheimer's disease brain and in age-matched control brains. The content of SRIF-like immunoreactivity (SRIF-LI) was found to be decreased in Alzheimer temporal cortex (Brodmann area 21) compared to control temporal cortex. The decreased content of SRIF was significantly correlated with the observed number of neuritic plaques and neurofibrillary tangles. No difference was observed in NPY-LI between Alzheimer cerebral cortex and control cortex. Furthermore, no correlations were observed between NPY content and plaque count, neurofibrillary tangle estimate or SRIF content despite widespread reports of NPY/SRIF coexistence. PMID- 2877421 TI - Coexistence of egg-laying hormone and alpha-bag cell peptide in bag cell neurons of Aplysia indicates that they are a peptidergic multitransmitter system. AB - Double-label immunocytochemistry reveals that immunoreactivity for two putative peptide transmitters, egg-laying hormone and alpha-bag cell peptide, co-exist in most bag cell somata and processes in the abdominal ganglion of the marine mollusc Aplysia. Together with previous physiological and biochemical data these findings indicate that the neuroendocrine bag cells are a multitransmitter system which utilizes two or more peptides derived from a common precursor. PMID- 2877422 TI - Somatostatin binding sites in human leptomeninx. AB - Specific binding sites for somatostatin (SRIF) have been visualized in the human leptomeninx by means of autoradiographical techniques using the stable SRIF octapeptide analog 125I-204-090 as radioligand. The binding sites are specific for SRIF since only biologically active SRIF analogs compete with the radioligand. The density of the binding sites is comparable to that of the adjacent cortical structure. The presence of SRIF binding sites in the human leptomeninx, together with the recent demonstration of SRIF binding sites in human meningiomas, strongly suggest that this peptide may play a role in the physiology of the leptomeninx. PMID- 2877423 TI - Sexual activity alters the concentration of amino acids in the cerebrospinal fluid of male rats. AB - The concentrations of amino acids were measured in cerebrospinal fluid samples obtained from freely moving male rats before sexual activity, immediately after ejaculation and after the end of the postejaculatory refractory period. The concentration of gamma-aminobutyric acid increased by more than 1000% after ejaculation, while the concentrations of Asp and Glu increased by about 200%. Consistent, but small decrements were found in the concentrations of Ser, Arg, Ala and Leu. Thus, the concentration of a major inhibitory neurotransmitter increases markedly in a physiological state when male rats are completely refractory to sexual stimuli. PMID- 2877425 TI - Plasticity in hippocampal excitatory amino acid receptors in Alzheimer's disease. AB - Entorhinal cell loss occurs in the course of Alzheimer's disease. In rodents, entorhinal lesions result in axon sprouting in the hippocampus. Quantitative autoradiography was used to examine the density and distribution of N-methyl-D aspartate (NMDA) and kainic acid (KA) receptors in human hippocampus obtained post-mortem from Alzheimer's disease patients and from age-matched controls. In Alzheimer's disease, there was an expanded distribution of the KA receptor field in the dentate gyrus, indicative of sprouting of the commissural and associational fibers. This regenerative response is thought to facilitate transmission, but in doing so it may also enhance vulnerability to excitotoxic mediated neuronal damage. No significant change was observed in the density or distribution of NMDA receptors. The distribution of these receptors does, however, correlate with the predilection for neurofibrillary tangles and neuritic plaques in hippocampal subfields. PMID- 2877424 TI - Action and localisation of neurotransmitters in the cat retina. PMID- 2877426 TI - Effects of benzodiazepines on acquisition and performance: a critical assessment. AB - Evidence related to the effects of benzodiazepines on learning and memory is reviewed in the contexts of human verbal learning studies and animal studies using both aversive and non-aversive paradigms. While the impairment of acquisition by benzodiazepines appears to be a robust phenomenon generalizing across species and experimental conditions, the impairment in the performance of an already-learned task by such drugs appears to be more restrictive and highly dependent upon experimental contingencies. Thus far, performance impairment appears to be found mainly in animal studies using non-aversive, food-motivated tasks, with such tasks being particularly well suited for investigating such a phenomenon. At present, there is a noticeable lack of knowledge regarding the neurochemical substrates underlying BDZ-induced impairment. Finally, some issues that may contribute to the presence or absence of a BDZ-induced performance impairment in published studies are briefly considered. PMID- 2877427 TI - HTLV 1 induced adult T cell leukaemia in New Zealand. PMID- 2877428 TI - Sulphasalazine in inflammatory bowel disease: recent advances. PMID- 2877429 TI - Glutathione synthesis in evolution: an Achilles' heel of human and other old world simian lenses. AB - The activities of gamma-glutamylcysteine synthetase (gamma-GCS) and glutathione synthetase, the two enzymes responsible for glutathione synthesis, were determined in adult lenses from representative species of eight mammalian orders. Lenses from Old World higher simians, including man, exhibited remarkably low gamma-GCS activity when compared to a prosimian and the other seven orders. In contrast, glutathione synthetase activity was comparable and relatively high in all orders. This, together with knowledge of its known lability and control mechanisms, suggests that gamma-GCS is a critical enzyme in the lens of the aging higher primate, whose very low and rate-limiting activity is a latent factor in the development of age-related cataract. PMID- 2877430 TI - [Sensitivity to various antibiotics of spiroplasmas isolated from mosquitoes in France]. AB - Spiroplasmas are helical mycoplasmas that play a significant role in plant diseases. They are also found in arthropods that are likely to bite humans, such as ticks and mosquitoes. These arthropods can act as vectors and therefore may be of epidemiologic significance. Furthermore, mainly on the grounds of morphologic evidence, spiroplasmas have been incriminated in the genesis of human Creutzfeld Jacob disease. We recovered six strains of Spiroplasma sp. from 1927 female mosquitoes. In vitro susceptibility of each strain to the following antibiotics was studied: tetracycline, oxytetracycline, doxycycline, erythromycin, chloramphenicol, rifampin, kanamycin, gentamicin and pefloxacin. Minimal inhibitory concentrations (MICs) were determined by dilution in liquid SP4 medium using microtiter plates. Plates were incubated for 24 to 48 hours at 30 degrees C. The inoculum contained approximately 5 X 10(5) CFU/ml. Each of the six strains was found to be highly susceptible to tetracycline, oxytetracycline, doxycycline, erythromycin, chloramphenicol and pefloxacin (MICs less than or equal to 0.16 microgram/ml, 0.63 microgram/ml, 0.08 microgram/ml, 0.16 microgram/ml and 0.32 microgram/ml respectively). On the opposite, the strains exhibited resistance to rifampin and variable degrees of susceptibility to kanamycin (12.5 micrograms/ml less than MIC less than 50 micrograms/ml) and gentamicin (3.12 micrograms/ml less than MIC less than 50 micrograms/ml). From our results, spiroplasmas seem to have more or less the same susceptibility to antibiotics as mycoplasmas. PMID- 2877431 TI - [Activity of cefotetan against anaerobic bacteria]. AB - We determined the susceptibility to antibiotics of 64 strains of obligate anaerobes. Tested bacterial strains were as follows: 28 Bacteroides fragilis, 22 Fusobacterium nucleatum, 10 Clostridium perfringens, and 4 Bacteroides bivius. Tested antibiotics were cefotetan, cefoxitin and piperacillin. Cefotaxime was tested against 20 Bacteroides fragilis strains. Bacteroides fragilis, which is the most resistant species, was susceptible to cefotetan, cefoxitin and piperacillin, with comparable MICs for these three drugs (0.5 to 16 micrograms/ml); cefotaxime was less effective (MICs = 0.5 to 128 micrograms/ml). Fusobacterium nucleatum and Clostridium perfringens were highly susceptible to cefotetan, cefoxitin and piperacillin. PMID- 2877433 TI - Clinical and immunological follow-up of pregnant women with Graves disease. AB - The clinical and immune status of 11 pregnant women with Graves disease was followed up. Compared with the status before pregnancy, a deterioration of thyrotoxicosis characterized by an increased Crooks index and an increase in the total T4 and TBG levels was found. Measurements of the TSAb-titre by two parallel methods also gave distinctly altered values. Fetal or maternal complications were noted in 5 of the 11 cases. One of the women gave birth to a thyrotoxic fetus. It is suggested that in thyrotoxicosis of medium or major severity associated with a persistent TSAb positivity the possibility of subtotal thyroidectomy should be considered. PMID- 2877432 TI - Effect of a beta-agonist nebulization on lung function in neonates with increased pulmonary resistance. AB - Pulmonary resistance is elevated early in preterm infants who later develop chronic lung disease. This early increase in pulmonary resistance may play a role in the development of severe bronchopulmonary dysplasia (BPD). A beta-2-agonist (isoetharine HCl) was used as an aerosol in 13 preterm infants with elevated pulmonary resistance. Their birthweight ranged from 880 to 1630 g, their gestational age from 27 to 34 weeks, and their post natal age from 3 to 18 days. All infants had required mechanical ventilation for respiratory distress syndrome and therefore were at risk to develop BPD. Pulmonary mechanics were measured before and 30 minutes after aerosol treatment, determining inspiratory and expiratory flow with a pneumotachometer and esophageal pressure through a water filled feeding tube. The treatment was well tolerated with no significant changes in blood pressure, heart rate, or respiratory rate. Pulmonary resistance decreased significantly from 130 +/- 35 cm H2O/L/sec to 89 +/- 24 cm H2O/L/sec after the treatment. Dynamic lung compliance increased in 11 of the 13 infants. It is concluded that beta-2-agonist nebulization is effective in reducing the early increase in pulmonary resistance that occurs in preterm infants who are at risk of developing BPD. This effect may be due to relaxation of bronchial smooth muscle, to improved mucociliary transport, and to a reduction in peribronchial edema. PMID- 2877434 TI - Effects of somatostatin on basal and stimulated pancreatic secretion in conscious rat. AB - The effects of somatostatin on pancreatic secretion were studied in conscious rats during diversion and recirculation of pancreatic juice. Pancreatic secretion was significantly inhibited by low doses (2 micrograms/kg/h) of somatostatin during diversion of pancreatic juice. The inhibitory effect was more marked on bicarbonate and protein output than on volume, while in bicarbonate and protein output a rebound effect was observed. These data suggest a combined inhibitory effect of somatostatin on endogenous CCK release and cholinergic mechanisms. During recirculation of pancreatic juice there was no rebound effect, thus only the inhibition of cholinergic mechanisms seems to be involved in the inhibitory effect of somatostatin. During recirculation, CCK-OP-stimulated bicarbonate and protein secretion was strongly inhibited by somatostatin. Even water secretion not stimulated by CCK-OP was significantly inhibited demonstrating a supplementary inhibitory effect on basal cholinergic mechanisms. Somatostatin decreased only slightly the synthetic secretin-stimulated water and bicarbonate secretion. The more effective inhibition of protein output was explained by an additive effect of somatostatin on basal cholinergic tone. PMID- 2877435 TI - An RFLP associated with pcDLeu2-14, a human T-cell differentiation antigen CD8 (Leu2) cDNA mapped to 2p12. PMID- 2877436 TI - TaqI and XbaI RFLPs detected with a human apo IV (Apo4) cDNA probe. PMID- 2877437 TI - An anonymous X-chromosomal clone identifying a frequent RFLP at Xp21-22 (HGM8 provisional no. DXS207). PMID- 2877438 TI - Pst I RFLP close to the LDL receptor gene. PMID- 2877439 TI - Sequence and transcription analysis of the Petunia mitochondrial gene for the ATP synthase proteolipid subunit. AB - We have sequenced the Petunia hybrida gene that specifies the proteolipid subunit of the mitochondrial Fo ATP synthase and have used this gene to investigate plant mitochondrial gene transcription. The Petunia atp 9 gene contains a single open reading frame capable of specifying a 77 amino acid-polypeptide that is homologous to bovine, fungal and maize proteolipid subunits. S1 protection identified 3 transcripts in a ratio of 1:5:100 in the Petunia tissues tested. The transcripts share a common 3' terminus but have 5' termini that map 528, 266, and 121 nucleotides upstream of the translation start site. The 5' terminus of the longest transcript maps to the sequence ATATAGTA, which is nearly identical to the yeast mitochondrial transcription initiation site ATATAAGTA. Primer extension analysis indicates that these two shorter transcripts are not due to splicing. The two shorter transcripts originate at sequences homologous to sites at 5' termini of two pea and maize genes. These consensus sequences may signal processing events other than splicing. PMID- 2877441 TI - Mutations in the mitochondrial oli1 gene of Saccharomyces cerevisiae affecting subunit 9 of the mitochondrial ATPase complex. PMID- 2877440 TI - A family of DNA sequences is reproducibly rearranged in the somatic nucleus of Tetrahymena. AB - A small family of DNA sequences is rearranged during the development of the somatic nucleus in Tetrahymena. The family is defined by 266 bp of highly conserved sequence which restriction mapping, hybridization and sequence analysis have shown is shared by a cloned micronuclear fragment and three sequences which constitute the macronuclear family. Genomic Southern hybridization experiments indicate there are five members of the family in micronuclear DNA. All of the family members are present in whole genome homozygotes and are therefore nonallelic. The three macronuclear sequences are all present in clonal cell lines and are reproducibly generated in every developing macronucleus. The rearrangement event begins 14 hours after conjugation is initiated and is nearly completed by 16 hours. PMID- 2877442 TI - The nervous system: transmitting the right signals. PMID- 2877443 TI - The effects of dietary fat and selenium on the development of preneoplastic lesions in rat liver. AB - In this study, the effects of dietary fat and selenium on the development of putative preneoplastic foci induced by aflatoxin B1 were examined. Rat hepatic gamma-glutamyl transpeptidase (GGT) activity, selenium-dependent glutathione peroxidase activity, glutathione, and total lipid were analyzed 3 and 13 weeks after the start of dietary and carcinogen treatment. Results indicate that high dietary fat has an enhancing effect on the development of preneoplastic foci. A high-fat, selenium-deficient diet resulted in an increase in foci development, but the increase was not significant. An interaction between aflatoxin and the two nutrients was also observed in liver glutathione content and GGT activity at Week 3. PMID- 2877444 TI - Neuroleptic-induced catatonia after abrupt withdrawal of amantadine during neuroleptic therapy. AB - Catatonic reactions to high-potency neuroleptic drugs have been described in the literature. Our patient developed neuroleptic-induced catatonia (NIC) after abrupt withdrawal of amantadine, a dopaminergic agent that has been implicated in neuroleptic malignant syndrome (NMS) on its discontinuation. This case report adds support to the hypothesis that NIC and NMS are 2 syndromes on a continuum of dopamine blockade, each of which may be treated with or uncovered by amantadine therapy. PMID- 2877445 TI - Cyclic antidepressant overdose in children: a proposed treatment protocol. AB - Cyclic antidepressant overdose is a major cause of drug overdose deaths and morbidity in the United States. The cyclic antidepressants are prescribed widely by primary care physicians and psychiatrists, and accidental overdose in children is not uncommon. Children have exhibited toxic effects with relatively small amounts of cyclic antidepressants. The management of cyclic antidepressant overdose is difficult because of the complex effects on the cardiovascular and nervous systems. The pertinent pharmacology of cyclic antidepressants in therapeutic amounts and in overdose is reviewed in this article. The clinical manifestations of cyclic antidepressant overdose are described. A protocol for effective management of cyclic antidepressant overdose in children is proposed. PMID- 2877446 TI - Alpha-neo-endorphin coexists with dynorphin-A(1-8) within intramurally lying perikarya of rat duodenum. AB - By the use of the immunofluorescent microscopic staining technique, adjacent serial sections through the rat duodenum were alternately stained with specific antisera directed to the opioid peptides alpha-neo-endorphin and dynorphin-A(1 8). alpha-Neo-endorphin immunoreactivity has been revealed exclusively within perikarya lying intramurally in the longitudinal muscle layer. These alpha-neo endorphin and dynorphin-A(1-8) immunoreactive perikarya were large in diameter, round in shape, contained a large and round nucleus, and were recognized only occasionally there. alpha-Neo-endorphin immunoreactivity was coexistent with dynorphin-A(1-8)-positive material within these perikarya. Since no alpha-neo endorphin material was detected within duodenal nerve fibres and terminals, it might be concluded that this peptide is further enzymatically cleaved to the opioid pentapeptide Leu-enkephalin during its axonal transport from intramural perikarya to nerve terminals and during its storage there. PMID- 2877447 TI - Affective illness in substance abusers. AB - The evaluation and treatment of substance abusers are complicated tasks, requiring a multifaceted approach. In addition to the patient's substance abuse problems, a substantial minority appear to be suffering from concurrent, nondrug related psychiatric disorders. The early identification of such individuals allows for the development of specific treatment strategies that address both the substance abuse and the associated nondrug psychopathology. On the other hand, attention to nondrug psychopathology should not preclude our simultaneously addressing the patient's substance abuse problem. Thus, manic depressive patients who are also alcoholic may need a treatment program that includes alcoholism counseling. Alcoholics Anonymous, and chronic administration of disulfiram in addition to lithium carbonate and a supportive psychotherapeutic relationship. As in other areas of medicine, attention to the "whole patient" is the sine qua non of good treatment. PMID- 2877448 TI - [Effect of methaxamine on mitral valve insufficiency associated with hypertrophic obstructive cardiomyopathy, mitral valve prolapse and rheumatic disease]. PMID- 2877449 TI - Hypertensive drugs and plasma kinins in rats. AB - The influence of phenylephrine (PHE), methoxamine (MET) and ephedrine (EPH) on kininogen and prekallikrein level in plasma was investigated in male Wistar rats. Simultaneously the effect of these drugs on blood pressure was monitored. No changes in kininogenesis were observed during the hypertension period (2 h after ip injection). The significant decrease in kininogen level (by 20-30%) was found 4 h after PHE (5 mg/kg) or EPH (40 mg/kg) and 4-12 h after MET (40 mg/kg) injection. The reduction of kallikrein utilization, indicating an increase in prekallikrein level in plasma, was noted only after PHE (by 34%) or MET (by 44%) administration. Phentolamine (REG) in a dose of 20 mg/kg, which counteracted the hypertensive effect of investigated drugs, abolished the influence of these drugs on kininogen level. The results indicate that the hypertension induced by alpha adrenoceptor agonists evokes the delayed activation of kininogenesis parallel to the secondary decrease in blood pressure. Such a reaction of kinin system seems to be related to primary alpha-adrenoceptor stimulation, not to the direct influence of hypertensive drugs on kinin system in rat plasma. PMID- 2877450 TI - [Neuropeptides and neurotransmission]. PMID- 2877451 TI - Current perspectives in treatment of angina pectoris. AB - The most appropriate treatment for a patient with angina pectoris depends on the underlying pathophysiologic process and whether any associated illness is present. Each patient's clinical history must be carefully reviewed so the hemodynamic process responsible for the clinical picture is understood. If symptoms are produced mostly by an increase in myocardial oxygen demand, efforts should be directed toward reducing the demand or improving coronary blood flow to meet the demand. If symptoms appear to occur secondary to vasospasm, treatment should be directed toward relief of spasm with potent vasodilating agents, such as calcium channel blockers. Most patients have a clinical picture consistent with mixed angina and may require combination therapy. Treatment of associated illnesses and the safety of pharmacologic agents used in their presence should be carefully considered. Finally, if treatment is to successfully reduce the incidence of serious cardiac events and prolong life, the goal of therapy should be relief of the total ischemic burden on the heart. PMID- 2877452 TI - Hypertension 1986. Evaluation and treatment--why and how. PMID- 2877453 TI - Are blood pressure surges associated with sympathetic stimulation aggravated by beta-adrenoceptor antagonist treatment? PMID- 2877454 TI - Can and should type A behaviour be changed? AB - Both Type A behaviour and the component of hostility can be reduced by a number of different psychological interventions and such reductions are associated with reduced cardiac morbidity in patients with coronary heart disease. Reductions in Type A behaviour are not associated with significant changes in other risk factors nor with unwanted side effects such as reduced professional effectiveness. PMID- 2877455 TI - Spontaneous splenic rupture in polyarteritis nodosa. AB - A 28 year old man presented with haematuria and renal failure. Renal arteriography revealed bleeding into the pelvis of a solitary right kidney from a hilar artery. Multiple aneurysms were noted in the splenic artery. The spleen subsequently ruptured spontaneously and was removed at laparotomy together with the right kidney. Histological examination of the spleen and kidney revealed an acute necrotizing vasculitis involving medium-sized and smaller arteries confirming a diagnosis of polyarteritis nodosa. An area of infarction involved a subcapsular area of the spleen. Spontaneous splenic rupture is a rare but important complication of systemic vasculitides. PMID- 2877456 TI - Primary structure of blood coagulation factor XIIIa (fibrinoligase, transglutaminase) from human placenta. AB - We have determined the primary structure of human placental factor XIIIa, an enzyme [fibrinoligase, transglutaminase, fibrin-stabilizing factor, EC 2.3.2.13 (protein-glutamine:amine gamma-glutamyltransferase)] that forms intermolecular isopeptide bonds between fibrin molecules as the last step in blood coagulation. Placental factor XIIIa is an unglycosylated polypeptide chain of 730 amino acid residues (Mr = 83,005) that appears to be identical to the a subunit of the plasma zymogen factor XIII. Ca2+-dependent activation of factor XIIIa by thrombin removes a blocked amino-terminal peptide and unmasks a reactive thiol group at Cys-314. A second specific cleavage after Lys-513 by thrombin inactivates factor XIIIa and produces an amino-terminal 56-kDa fragment and a 24-kDa fragment. The amino acid sequence of factor XIIIa is unique and does not exhibit internal homology, but its active center is similar to that of the thiol proteases. The probable Ca2+-binding site of factor XIIIa has been identified by homology to the high-affinity sites in calmodulins. Knowledge of the primary structure of factor XIIIa will aid elucidation of the mechanism of its enzymatic action and that of the many tissue transglutaminases of which it is the prototype. This will also facilitate production of factor XIIIa by recombinant DNA technology for use in treatment of congenital factor XIII deficiencies and in the postoperative healing of wounds. PMID- 2877457 TI - Characterization of cDNA coding for human factor XIIIa. AB - A cDNA library prepared from human placenta has been screened for sequences coding for factor XIIIa, the enzymatically active subunit of the factor XIII complex that stabilizes blood clots through crosslinking of fibrin molecules. Two oligonucleotides, based on the amino acid sequences of tryptic peptides of factor XIIIa, were used as hybridization probes. Of 0.36 X 10(6) independent recombinants, 1 clone was identified that hybridized to both probes. The insert of 1704 base pairs coded for the amino-terminal 541 amino acid residues of the mature factor XIIIa molecule. Blot-hybridization analysis using this cDNA as a probe showed that the factor XIIIa mRNA from placenta has a size of approximately 4000 bases. The insert was used to rescreen cDNA libraries and to identify further factor XIIIa-specific sequences. The total length of the isolated factor XIIIa cDNA is 3905 bases, and it codes for a protein of 732 amino acids. In spite of the presence of factor XIII in blood plasma, we could not identify a leader sequence typical for secreted proteins. PMID- 2877458 TI - Sequence analysis of the cDNA encoding human liver glycogen phosphorylase reveals tissue-specific codon usage. AB - We have cloned the cDNA encoding glycogen phosphorylase (1,4-alpha-D glucan:orthophosphate alpha-D-glucosyl-transferase, EC 2.4.1.1) from human liver. Blot-hybridization analysis using a large fragment of the cDNA to probe mRNA from rabbit brain, muscle, and liver tissues shows preferential hybridization to liver RNA. Determination of the entire nucleotide sequence of the liver message has allowed a comparison with the previously determined rabbit muscle phosphorylase sequence. Despite an amino acid identity of 80%, the two cDNAs exhibit a remarkable divergence in G+C content. In the muscle phosphorylase sequence, 86% of the nucleotides at the third codon position are either deoxyguanosine or deoxycytidine residues, while in the liver homolog the figure is only 60%, resulting in a strikingly different pattern of codon usage throughout most of the sequence. The liver phosphorylase cDNA appears to represent an evolutionary mosaic; the segment encoding the N-terminal 80 amino acids contains greater than 90% G+C at the third codon position. A survey of other published mammalian cDNA sequences reveals that the data for liver and muscle phosphorylases reflects a bias in codon usage patterns in liver and muscle coding sequences in general. PMID- 2877459 TI - Polyadenylylation of an mRNA precursor occurs independently of transcription by RNA polymerase II in vivo. AB - Most eukaryotic messenger RNAs are transcribed as precursor molecules that must be processed by capping, splicing, 3' cleavage, and polyadenylylation to yield mature mRNAs. An important, unresolved issue is whether any of these reactions are linked either to transcription by RNA polymerase II or to each other. To address one aspect of this question, we constructed a chimeric gene containing an RNA polymerase III promoter (the adenovirus VAI promoter) fused to the body and 3'-flanking sequences of a protein-coding gene (the herpesvirus tk gene). Here we show that this hybrid gene was transcribed from the RNA polymerase III promoter following transfection of human 293 cells and that the transcripts produced were stable and efficiently transported to the cytoplasm. Although a significant proportion of the transcripts were prematurely terminated at specific sites within the gene, a high percentage of the full-length RNA was accurately cleaved and polyadenylylated. These results demonstrate that cleavage and polyadenylylation of mRNA precursors are not obligatorily coupled to transcription by RNA polymerase II in vivo. PMID- 2877460 TI - Serotonin initiates and autoamplifies its own synthesis during mouse central nervous system development. AB - Some cells from cultured embryonic mouse hypothalamus were found to express aromatic-L-amino acid decarboxylase (EC 4.1.1.28) activity and serotonin uptake and storage. These neuron-like cells differed from serotoninergic neurons in cultured embryonic mouse brain stem since they did not contain tryptophan hydroxylase. We studied the effect of the serotonin agonist 8-hydroxy-2-[di-(n propyl)amino]tetralin on neuronal differentiation of hypothalamic cells from 12- to 15-day embryos. Repeated treatment of cultures with the serotonin agonist for 10 days resulted in an increased number of serotonin cells containing high levels of decarboxylase activity. Both the increase in cell numbers and the elevated decarboxylase activity could be suppressed by the addition of the serotonin antagonist metergoline to the culture medium. These data show that serotonin (or an agonist), acting on specific receptors, can initiate and amplify its own synthesis in embryonic hypothalamic neurons, as observed in the primitive hypothalamic nerve cell line F7 [De Vitry, F., Catelon, J., Dubois, M., Thibault, J., Barritault, D., Courty, J., Bourgoin, S. & Hamon, M. (1986) Neurochem. Int. 9, 43-53]. Such an autocrine-like mechanism may be active during nervous system development and may represent an example of learning at the cellular level. PMID- 2877461 TI - Antibody-targeted photolysis: selective photodestruction of human T-cell leukemia cells using monoclonal antibody-chlorin e6 conjugates. AB - Selective in vitro photodestruction of HPB-ALL human T-cell leukemia cells was accomplished using the photosensitizer chlorin e6 coupled through dextran molecules to an anti-T-cell monoclonal antibody (mAb), anti-Leu-1. Conjugates with mAb/chlorin molar ratios as high as 1:36 retained mAb binding activity, and the absorption spectrum and quantum efficiency for singlet oxygen production of bound chlorin (0.7 +/- 0.2) were unchanged from that of the free photosensitizer. Phototoxicity, as measured by a clonogenic assay and by uptake of ethidium bromide, was dependent on the doses of both mAb-chlorin and 630- to 670-nm light, was enhanced by 2H2O, and was observed only in target populations that bound the mAb. Similarly, free chlorin e6 in solution had no photodynamic effect in amounts 100 times more than that carried by the mAb. For this antibody-targeted system, approximately 10(10) molecules of singlet oxygen were necessary to kill a cell. PMID- 2877462 TI - 1,3-Di(2-[5-3H]tolyl)guanidine: a selective ligand that labels sigma-type receptors for psychotomimetic opiates and antipsychotic drugs. AB - Brain sigma-type receptors are thought to mediate hallucinogenic effects of certain benzomorphan opiates in humans. The biochemical characterization of sigma receptors has been difficult because of the lack of potent and selective ligands. We report here the synthesis and characterization of a tritiated, symmetrically substituted guanidine derivative, 1,3-di(2-[5-3H]tolyl)guanidine ([3H]Tol2Gdn), that binds with high affinity to a single population of binding sites in guinea pig brain membrane preparations. The [3H]Tol2Gdn binding site displays stereoselectivity for dextrorotatory optical isomers of benzomorphan opiates known to have sigma-type behavioral effects. Furthermore, the [3H]Tol2Gdn binding site has a high affinity for haloperidol and for phenothiazine antipsychotics, which have antihallucinatory properties in humans. The drug-selectivity profile of [3H]Tol2Gdn binding closely correlates with the drug-selectivity profile of tritiated (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [+)-[3H]3-PPP) binding to guinea pig brain membrane receptors. (+)-[3H]3-PPP has been proposed to be a selective sigma-receptor ligand [Largent, B. L., Gundlach, A. L. & Snyder, S. H. (1984) Proc. Natl. Acad. Sci. USA 82, 4983-4987]. Receptor autoradiography using [3H]Tol2Gdn on slide-mounted rat and guinea pig brain sections reveals a heterogeneous distribution pattern of enriched binding in limbic and sensorimotor structures of the brain. These results indicate that [3H]Tol2Gdn is a selective ligand for the sigma-site. Availability of this sigma-receptor probe should greatly facilitate the physiological, biochemical, and pharmacological characterization of sigma receptors in brain. PMID- 2877463 TI - Transplantation of ventral mesencephalic anlagen to hosts with genetic nigrostriatal dopamine deficiency. AB - Attempts to reconstruct the damaged nigrostriatal pathway in experimental models of Parkinson disease have thus far been carried out in animals with neurotoxically induced dopamine deficiency. The present study establishes the weaver (wv/wv) mutant mouse as a genetic model of chronic striatal dopamine denervation by demonstrating a marked decrease of tyrosine hydroxylase immunoreactive neurons in the substantia nigra pars compacta. Moreover, grafts of embryonic ventral mesencephalon taken from genetically normal mice and transplanted into the lateral ventricle of adult weaver mutants can survive and grow in the mutant host environment, express tyrosine hydroxylase immunoreactivity, and reinnervate the target regions of the recipient. These results provide evidence of integration of graft and host tissue and suggest that transplantation of dopamine neurons may be effectively applied to overcome nigrostriatal degeneration of genetic etiology. PMID- 2877465 TI - Afterimage-like effects in the motion-sensitive neuron H1. AB - A powerful effect resembling an afterimage is demonstrated on the pathway to the motion-sensitive neuron H1. This effect is independent of the locally generated gain control described in an earlier paper (Maddess & Laughlin 1985, Proc. R. Soc. Lond. B 225, 251). The afterimage, produced across the eye by a stationary pattern, causes the sensitivity to movement to be different according to the local stimulus history, and the effects of low-contrast (0.1) patterns, presented for as little as a few hundred milliseconds, remain for up to 2 s. Moving patterns interact with the afterimage to modulate the spike rate of H1. The afterimage increases with contrast but saturates at contrasts above 0.5. Low spatial frequencies generate afterimages less effectively than moderate ones; this result indicates that the afterimage process could lie at, or after, lateral inhibition between tonic units. This is supported by the fact that the altered sensitivity profiles generated by single bright and dark vertical bars initially resemble Mach bands. However, this character alters as the afterimage decays, and the depression of H1's response to moving bright stimuli, produced by the afterimage of a dark bar, continues to grow for up to 1 s after the adapting bar is removed. A short-lived (0.5 s) reduction of H1's directional selectivity accompanies strong afterimage formation. All these factors, especially the saturation at low contrasts and the spatial frequency tuning, rule out light adaptation by photoreceptors as the afterimage source. Luminances used were also low enough to exclude influence by the pupil mechanism. Lastly, responses to patterns that are occasionally jumped by large or small distances are broadened by stimuli that produce an afterimage. Responses to small displacements have previously been described as 'velocity impulse responses' (Srinivasan 1983, Vision Res. 23, 659; Zaagman et al. 1983, IEEE Trans. SMC 13, 900) and so the response broadening (stimulus blurring) can be taken as a reduction of the fly's temporal resolution of moving objects. Previously reported work shows that afterimages seen in humans and the effect reported here act over the same range of temporal frequencies rather than retinal drift speeds. This may suggest an important role for afterimage-like effects in the processing of the low temporal frequency components of moving images. Certainly, the fly's afterimage system reduces the visibility of moving objects within patches of an image that, have on average, contained slowly varying motion signals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2877464 TI - The structure and symmetry of simple-cell receptive-field profiles in the cat's visual cortex. AB - Receptive fields of simple cells in the cat visual cortex have recently been discussed in relation to the 'theory of communication' proposed by Gabor (1946). A number of investigators have suggested that the line-weighting functions, as measured orthogonal to the preferred orientation, may be best described as the product of a Gaussian envelope and a sinusoid (i.e. a Gabor function). Following Gabor's theory of 'basis' functions, it has also been suggested that simple cells can be categorized into even- and odd-symmetric categories. Based on the receptive field profiles of 46 simple cells recorded from cat visual cortex, our analysis provides a quantitative description of both the receptive-field envelope and the receptive-field 'symmetry' of each of the 46 cells. The results support the notion that, to a first approximation, Gabor functions with three free parameters (envelope width, carrier frequency and carrier phase) provide a good description of the receptive-field profiles. However, our analysis does not support the notion that simple cells generally fit into even- and odd-symmetric categories. PMID- 2877466 TI - Behavioral deficits induced by low doses of apomorphine in rats: evidence for a motivational and cognitive dysfunction which discriminates among neuroleptic drugs. AB - In order to further assess the alterations (motor, motivational or cognitive) that might underlie animal behavioral deficits associated with a reduced dopamine transmission, the effects of apomorphine at doses thought to stimulate dopaminergic autoreceptors were studied on rat operant behavior. Apomorphine (30 micrograms/kg SC) decreased the number of food rewards obtained, when rats trained on a continuous reinforced schedule were shifted to schedules of fixed ratio higher than 2:FR3, FR4, and FR8. In rats shifted to a FR4 schedule, apomorphine (7.5, 15, 30, 60 micrograms/kg SC) dose-relatedly reduced the number of rewards obtained. In rats subjected to previous extinction sessions, apomorphine (30 micrograms/kg) did not affect lever pressing reinstated on presentation of primary reinforcers but inhibited responding renewed on presentation of secondary reinforcers. Under a FR(3 + 1) schedule where the last (rewarded) response was distinct from the initial (non-rewarded) responses, the detrimental effect of apomorphine on response rates was considerably weaker than under a conventional FR4 schedule. The reward deficits caused by apomorphine under the FR4 schedule were dose-dependently and completely reversed by amisulpride (0.125, 0.25, 0.5, 1 and 2 mg/kg), pimozide (0.125 mg/kg), sulpiride (8, 16, 32 and 64 mg/kg), but not by conventional neuroleptics (namely chlorpromazine, fluphenazine, haloperidol, metoclopramide and thioridazine). It is suggested that behavioral deficits associated with a reduced dopamine transmission such as that caused by low doses of apomorphine involve motivational and cognitive dysfunctions rather than motor impairments. In account of its differential sensitivity to neuroleptic drugs, apomorphine-induced deficit might have some relevance for a further delineation of the mechanisms of action of these compounds. PMID- 2877467 TI - Influence of naloxone on H2-receptor blocker drugs effects in the "behavioral despair" test. AB - The influence of H2-receptor blockers (ranitidine and cimetidine) in a "behavioral despair" test in mice was studied. Both ranitidine and cimetidine shortened the immobility time at 20 mg X kg-1 and 30 mg X kg-1. Naloxone at 2 mg X kg-1 antagonized this reduction in immobility time. PMID- 2877468 TI - Biological basis of drug-induced tolerance, rebound, and dependence. Contribution of recent research on benzodiazepines. AB - It is proposed that the general biological basis of acquired drug tolerance, of rebound phenomena induced by drugs, and of physiological dependence is a drug induced adaptive syndrome. Several examples of the compensatory molecular, cellular and system responses are presented that may be induced by the primary drug-induced perturbation in the base-line of various neuronal and non-neuronal activities. Some form of adaptive syndrome is the inevitable consequence of the reciprocal interaction between most or all major classes of drugs and the organism. Knowledge of the molecular and cellular targets of drugs provides an understanding of the various phenomena of the drug-induced adaptive syndrome as well as of the means to avoid or attenuate their potential danger for subjects chronically exposed to drugs. Psychological dependence is discussed as a further factor which, in combination with drug-induced adaptive changes, facilitates drug abuse and, in particular, addiction or drug-seeking behavior. The phenomena of the adaptive syndrome induced by benzodiazepines are discussed against the background of medical science's present advanced knowledge of the molecular and synaptic mechanisms of action of this class of drugs. PMID- 2877469 TI - The influence of mechanical conditions on the healing of experimental fractures in the rabbit: a microscopical study. PMID- 2877470 TI - Bandage backfall: labyrinthine and non-labyrinthine components. AB - A cataleptic animal clings in a vertical position, unmoving, for abnormally long periods by supporting some of its weight on its hindlegs, grasping with the forepaws, flexing its forelimbs, and holding the head horizontal. When the head is snugly wrapped with a bandage, the head slowly falls backward, the neck hyperextends, the forelimbs extend and the grasp is released, resulting in the animal falling backward to the ground. It was earlier suggested that in cataleptic animals, the bandage inhibits vestibular and kinesthetic mechanisms of head support, yielding the backfall sequence [35]. However, preliminary experiments showed that labyrinthectomized rats made cataleptic by haloperidol fall backwards when placed in a vertical clinging position, even without a bandage, suggesting that in the rat the bandage-backfall reaction depends only on the vestibular system. In the present paper, this result is verified but, by additional experiments, the latter conclusion is shown to be incorrect. In labyrinthectomized rats made cataleptic by other means (lateral hypothalamic damage, or bulbocapnine), backfall from clinging did not occur unless a bandage was applied. Therefore, the bandage does indeed appear to inhibit the kinesthetic mechanisms that maintain head support in labyrinthectomized cataleptic rats. Haloperidol, particularly in high doses, greatly weakens postural support in labyrinthectomized rats (causing the animal to sag down and fall back when clinging), although the effect is not detectable in rats with labyrinths intact. However, labyrinthectomy reveals that the bandage can trigger an active dorsiflexion of the neck which in itself appears to inhibit clinging and righting. Bandage-induced dorsiflexion is present to a much lesser degree in intact animals, indicating that labyrinthine mechanisms inhibit the dorsiflexion reflex. Therefore, in the intact, cataleptic rat the bandage backfall reaction appears to be produced by the combined effects of a passive component (inhibition of kinesthetic support mechanisms), and an active component (elicitation of dorsiflexion of the neck). PMID- 2877471 TI - Alterations in physiological functions and in brain monoamine content in the sympathectomized rats. AB - In the present study, we conducted pre-ganglionic decentralization (or sympathetic trunk resection) of the superior cervical ganglia and observed alterations in several physiological functions and in the monoamine content of different brain regions. Over an ambient temperature range of 8-30 degrees C, these sympathectomized rats maintained their rectal temperatures within a normal limit displayed by the intact controls. These sympathectomized animals, although showing no change in the level of spontaneous pain threshold or motor activity, did display an increased sensitivity of analgesic responses to morphine administration or locomotor stimulant responses to amphetamine administration. Biochemical examination revealed that these sympathectomized animals had a higher level of norepinephrine, dopamine or 5-hydroxytryptamine in the hypothalamus, as well as a higher level of dopamine in the corpus striatum. However, in the brainstem, these sympathectomized animals had a unaltered monoamine level. The data indicate that, in a sympathectomized condition, changes in the monoamine content of different brain regions may be correlated with the above-mentioned alterations in somatosensory and motor neural functions. PMID- 2877472 TI - Low-dose dependence in chronic benzodiazepine users: a preliminary report on 119 patients. PMID- 2877474 TI - The behavioral effects of benzodiazepines following long-term use. PMID- 2877473 TI - Long-term administration of benzodiazepines: pharmacokinetic versus pharmacodynamic tolerance. PMID- 2877475 TI - Use of psychotropics in cancer patients. PMID- 2877476 TI - Anxiety: drug treatments for biologically determined disorders. PMID- 2877478 TI - [Value of labetalol for controlled hypotension in surgery of otospongiosis]. PMID- 2877477 TI - Dietary alpha-linolenic acid deficiency in the rat. I. Effects on reproduction and postnatal growth. AB - The effects of a dietary alpha-linolenic acid (18 : 3 n-3) deficiency on reproduction and postnatal growth in rats were studied during 3 successive gestations and 4 successive generations. Female rats received respectively a semi synthetic diet in which the lipids were incorporated either as sunflower oil at 1.5% (deficient diet) or as soya oil at 1.87% (control diet). Both diets supplied the same amount of linoleic acid (18 : 2 n-6) (940 mg/100 g of diet), but the sunflower oil supplied 22 times less alpha-linolenic acid than the soya diet (6 mg vs 130 mg/100 g of diet). The results showed that, in our experimental conditions, the alpha-linolenic acid deficiency had no effect on fecundity (% of pregnant females), fertility (number of pups/litter), pup birth weight, food intake and weight of pregnant or lactating females, or pup growth during suckling. However, this deficiency did cause abnormally high rates of perinatal mortality from birth to postpartum day 3, namely on the average, for successive gestations: 18.5% in deficient pups vs 5.2% in the controls, and for successive generations: 16.6% in deficient pups vs 5.3% in the controls. Rat n-3 PUFA requirement during reproduction has been discussed; it appears to be more than 100 mg/100 g of feed. But this need should also be estimated in relation to n-6 PUFA supply; for female rats during reproduction, the ratio n-6: n-3 should be less than 10. PMID- 2877479 TI - [Malignant lymphoma, ORL localization, and the presence of anti-HTLV-I antibodies in Martinique]. PMID- 2877480 TI - Swedish trial in old patients with hypertension. A prospective multicentre study in Swedish primary health care. AB - The Swedish trial in old patients with hypertension was initiated by the Swedish League against Hypertension. It will be conducted as a prospective multicentre study in Swedish primary health care, and will comprise approximately 2 000 patients on active treatment and 2 000 on placebo to be studied for three years. The primary goal with this study is to investigate whether pharmacological treatment of hypertension in men and women aged 70-84 years will reduce the incidence of fatal and nonfatal cardiac and cerebrovascular disease. Before starting the main trial a pilot study comprising 400 patients will be carried out during one year to evaluate all logistical aspects of the study. This pilot study commenced in October 1985. PMID- 2877482 TI - [Secondary prevention following myocardial infarct]. PMID- 2877483 TI - [Prevention of arrhythmia in myocardial infarct (secondary prevention)]. PMID- 2877484 TI - [Round-table discussion "Drug prophylaxis of heart infarct"]. PMID- 2877481 TI - [How can the risk of heart infarction be reduced in hypertensive patients?]. PMID- 2877485 TI - [Allergy to Hymenoptera]. PMID- 2877486 TI - Comparative study of two benzodiazepines ("diazepam" versus "nitrazepam") in the treatment of postneuroleptic tardive dyskinesia. PMID- 2877487 TI - Insulin and glucose decreases the capacity of urea-N synthesis in the rat. AB - The relationship between insulin concentration (32-980 mU/l) and the capacity of urea-N synthesis (CUNS) was investigated with alanine as nitrogen source in 26 nephrectomized rats. The blood glucose concentration was kept constant by the 'glucose clamp' technique, and the endocrine pancreatic response was controlled by somatostatin. The CUNS was determined as the accumulation of urea corrected for intestinal hydrolysis at a constant amino acid concentration within the interval 7.3-11.6 mmol/l. At insulin concentration above 200 mU/l CUNS was decreased from 10 to 6 mumol (min X 100 g body wt)-1. At lower insulin concentrations the decrease was proportional. Hyperglycaemia 14.8 mmol/l decreased CUNS to 6.3 mumol (min X 100 g body wt)-1. The basal rate of urea-N synthesis was reduced from 3.8 to 1.9 mumol (min X 100 g body wt)-1 by insulin concentrations above 200 mU/l. The estimated alanine elimination (5.8 mumol(min X 100 g body wt)-1) was unchanged by insulin and reduced to 3.3 mumol(min X 100 g body wt)-1) by hyperglycaemia. Somatostatin infusion had no effect on CUNS or alanine elimination. It is suggested that the capacity of urea-N synthesis is subject to short term regulation independently by insulin and glucose. PMID- 2877488 TI - Effect of somatostatin on 133Xe clearance from colonic mucosa before and after local nervous blockade in unanaesthetized man. AB - The effect of intravenous somatostatin bolus on mucosal and submucosal blood flow in six patients with colostomies was studied with the local 133Xe clearance technique. Mucosal and submucosal blood flow decreased by 28% after somatostatin injection. After induction of local nervous blockade by infiltrating the labelled area of the mucosal membrane with lidocaine the reduction in blood flow caused by somatostatin was abolished. These observations suggest that the vasoconstrictor effect of somatostatin is mediated by neurogenic mechanisms. PMID- 2877489 TI - Effects of H2-receptor antagonists on the rat liver after partial hepatectomy or carbon tetrachloride-induced hepatic injury. AB - A total of 512 male rats were used to investigate the effects of H2-receptor antagonists on the liver after two-thirds hepatectomy or after carbon tetrachloride (CCl4)-induced hepatic injury. The serum aminotransferase levels in hepatectomy rats were significantly elevated as compared with those of rats with the sham operation 1 and 2 days after the operation. However, there were no differences in the serum aminotransferase levels and liver regeneration rates among the groups of hepatectomy rats who were treated with saline, cimetidine, or ranitidine. The injections of cimetidine or ranitidine did not induce a significant increase in serum amino-transferase levels or increase the severity of liver cell necrosis in CCl4-treated rats, as compared with the CCl4-treated rats who received saline injection. Thus, our data indicate that H2-receptor antagonists do not inhibit liver regeneration in rats after two-thirds hepatectomy or exert a detrimental effect on the liver cell necrosis in rats after CCl4-induced hepatic injury. PMID- 2877490 TI - Colloidal bismuth subcitrate and two different dosages of cimetidine in the treatment of resistant duodenal ulcer. Preliminary results. AB - The use of colloidal bismuth subcitrate (CBS) has been recently suggested for cimetidine-resistant duodenal ulcers. We have therefore compared the activity of CBS with that of two different doses of cimetidine in patients whose duodenal ulcers had not healed after 8 weeks of therapy with cimetidine, 1.2 g, or ranitidine, 300 mg/day. Forty-three patients (35 men and 8 women) were randomly allocated to one of the following oral regimens: CBS, 120 mg 4 times a day, or cimetidine (C), 400 mg 3 times a day, or cimetidine, 400 mg at meals plus 800 mg at bedtime, for 4-8 weeks. The interim analysis after 4 weeks of treatment showed similar percentages of healing in the two cimetidine schedules (46.7% with C, 1.2 g, and 42.9% with C, 2 g, respectively); conversely, CBS treatment resulted in a significantly higher healing rate as compared with both C, 1.2 g, and C, 2 g (P less than 0.05). These findings suggest that resistant duodenal ulcers are more responsive to cytoprotective agents than to antisecretory compounds. PMID- 2877491 TI - [Prevention of ulcer disease]. AB - H2-receptor antagonists, sucralfate, pirenzepine and antacids are effective, when given prophylactically, in preventing relapse of peptic ulcer. H2-receptor antagonists and sucralfate are the most widely used and are virtually free of side effects. Cessation of smoking, a balanced diet and a calm life-style are also part of the prophylaxis. The incidence of relapse is reduced by 50-80% over a period of 1-2 years. The economic and clinical benefits of prophylaxis are shown. It is indicated in cases of chronic, relapsing ulcers; complicated ulcers; in medically compromised subjects and in those with heavy responsibilities. Prophylaxis is unduly costly when given after a first episode of peptic ulcer or when episodes are infrequent. For patients with one or two episodes a year the decision to give prophylaxis depends on the patient's wishes. Prophylaxis of stress-induced haemorrhagic lesions depends on the securing of an intragastric pH greater than 3.5-5, usually achieved by hourly administration of antacids. Methylated prostaglandins and H2-receptor antagonists can prevent drug induced peptic lesions. Under the protection of one of these drugs it is possible to continue antiinflammatory treatment at the lowest possible dose. PMID- 2877492 TI - A pseudoautosomal gene in man. AB - The X/Y homologous gene MIC2 was shown to exchange between the sex chromosomes, thus demonstrating that it is a pseudoautosomal gene in man. MIC2 recombines with the sex-determining gene(s) TDF at a frequency of 2 to 3 percent. It is the most proximal pseudoautosomal locus thus far described and as such is an important marker for use in studies directed towards the isolation of TDF. PMID- 2877493 TI - Drug resistance of cancer cells probed. PMID- 2877494 TI - Thrombin binding to fibrin is necessary for fibrin polymers to enhance factor XIIIa formation. PMID- 2877495 TI - HTLV and human leukemia: perspectives 1986. PMID- 2877496 TI - [Immunoreactive dynorphin B in the central nervous system of the mouse and its high performance liquid chromatograph (HPLC) analysis]. PMID- 2877497 TI - [Changes in pulmonary arterial pressure during acute respiratory distress syndrome caused by injection of oleic acid in rabbits]. PMID- 2877498 TI - Clostridial infections of the lungs and pleura. PMID- 2877499 TI - Retrorectal tumor: is biopsy risky? AB - A 55-year-old white man with an extensive retrorectal tumor died after transrectal needle biopsy. The indications and methods for biopsy of tumors in this location are controversial and are not well delineated in the literature. When resection seems unlikely or risky, or if a neoplasm is suspected which could be treated by nonsurgical means, biopsy is indicated. Antibiotics with aerobic and anaerobic coverage should be given prophylactically. When CT scan or sigmoidoscopic findings suggest a necrotic tumor, the transrectal approach should be avoided. PMID- 2877500 TI - [Conservative treatment of peptic ulcer]. PMID- 2877501 TI - [Livedo racemosa and polyneuropathy in periarteritis nodosa]. PMID- 2877503 TI - Regulation of thyrotrophin secretion. AB - Substantial advances in understanding the regulation of thyrotrophin (TSH) secretion have been made during the past decade. The hypothalamic tripeptide, thyrotrophin-releasing hormone, is the major stimulator of TSH secretion, and thyroid hormones exert the major inhibitory influences on TSH secretion. Other hypothalamic peptides, biogenic amines and steroid hormones modulate TSH secretion. Basal serum TSH measurement is mainly of value in diagnosing primary hypothyroidism, but because the lower limit of the normal range of TSH is not clearly defined, dynamic measurements of TSH secretion are used in preference to basal measurements in assessing other disorders of the hypothalamopituitary thyroid axis. PMID- 2877505 TI - Conservative treatment of external pancreatic fistulas with parenteral nutrition alone or in combination with continuous intravenous infusion of somatostatin, glucagon or calcitonin. AB - Treatment with total parenteral nutrition (TPN) alone or combined with continuous intravenous infusion of either somatostatin or calcitonin or glucagon have been carried out upon 45 patients with a high output external pancreatic fistula. No significant difference among these treatment schedules was observed in the percentage of closure of fistulas (85 to 100 per cent of the patients), but patients treated with TPN plus somatostatin had the fistulas close within a significantly (p = 0.000028) shorter period of time. Moreover, this treatment was associated with the strongest inhibition of the output from the fistula (minus 82.3 per cent). Since treatment with somatostatin was not accompanied by any side effect, was followed by a quite rapid closure of the fistulas and allowed an estimated economic savings of about $2,100.00 dollars per patient, it seems to be advisable in the conservative treatment of external pancreatic fistulas. PMID- 2877504 TI - Kallmann's syndrome with unilateral renal agenesis. A case report. AB - A case of Kallmann's syndrome (hypogonadotrophic eunochoidism plus anosmia) in which further investigation revealed the association of unilateral renal agenesis is described. The importance of excretory urography in the investigation of patients with Kallmann's syndrome is stressed. PMID- 2877502 TI - A survey of human T-cell leukaemia virus type I antibodies in patients with malignant disease in the Witwatersrand area. AB - The prevalence of antibodies to human T-cell leukaemia virus type I in Africa ranges from 2% to 21% according to the geographical area surveyed. Most studies suggest that the background infection rate in children is low. In paediatric patients with malignant disease in the Witwatersrand area the prevalence is low (1%), whereas a seemingly high rate is found in healthy black children from a restricted rural area (7%). Further, the antibody prevalence in adult whites with lymphoproliferative disease is low (1%) compared with that in blacks with malignant disease (6%). There also appears to be a higher prevalence of positive results in black women (7%) than in black men (4%). PMID- 2877506 TI - Small bowel fistulas treated with somatostatin: preliminary results. AB - Small bowel cutaneous fistula appearing after laparotomy was treated with the tetradecapeptide somatostatin in six patients to reduce the volume and enzyme content of the intestinal secretion. Continuous intravenous infusion of somatostatin diminished output from the fistula in all cases. Spontaneous fistula closure occurred after 11 to 33 days of treatment in four patients. There were no complications such as sepsis, peritonitis, or wound or skin problems from the contact with intestinal secretion. The hospital stay ranged from 19 to 50 days and bowel function was restored to normal. These preliminary results indicated that somatostatin can promote healing of small bowel fistula by inhibiting intestinal secretions. PMID- 2877507 TI - Platelet microtubules in clot structure formation and contractile force generation: investigation of a controversy. AB - Whether platelet microtubules are involved in clot retraction/contraction has been controversial. To address this question we have simultaneously measured two clotting parameters, clot structural rigidity and isometric contractile force, using a rheological technique. For recalcified PRP clots these two parameters began rising together at about 15 min after CaCl2 addition. In the concentration range affecting microtubule organization in platelets, colchicine, vinca alkaloids and taxol demonstrated insignificant effects on both clotting parameters of a recalcified PRP clot. For PRP clots induced by adding small amounts of exogenous thrombin, the kinetic curves of clot rigidity were biphasic and without a lag time. The first phase corresponded to a platelet-independent network forming process, while the second phase corresponded to a platelet dependent process. These PRP clots began generating contractile force at the onset of the second phase. For both rigidity and force parameters, only the second phase of clotting kinetics was retarded by microtubule affecting reagents. When PRP samples were clotted by adding a mixture of CaCl2 and thrombin, the second phase clotting was accelerated and became superimposed on the first phase. The inhibitory effects of microtubule affecting reagents became less pronounced. Thrombin clotting of a two-component system (washed platelets/purified fibrinogen) was also biphasic, with the second phase being microtubule-dependent. In conclusion, platelet microtubules are important in PRP clotted with low concentrations of thrombin, during which fibrin network formation precedes platelet-fibrin interactions. On the other hand they are unimportant if a PRP clot is induced by recalcification, during which the fibrin network is constructed in the presence of platelet-fibrin interactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877509 TI - Evidence that the heads of ADH-sensitive aggrephores are clathrin-coated vesicles: implications for aggrephore structure and function. AB - Antidiuretic hormone (ADH) induces the fusion of long tubular organelles (aggrephores) with the luminal membrane of the receptor cell, and the delivery of particle aggregates to the membrane. Water flow is believed to take place through the particles. Nothing is known about the origin of the particle aggregates, their incorporation into the aggrephores, or the possible relationship of the aggrephores to the vesicular traffic that takes place in the epithelial cell. In the present studies of the ADH-sensitive epithelial cells of the toad urinary bladder, we have found that the spherical heads of the aggrephores appear to be clathrin-coated vesicles. We propose that vesicles originating from sites such as the Golgi or the luminal membrane may be engaged in aggrephore assembly, the resupply of particle aggregates to the aggrephores, and/or the removal of aggregates, and that the aggrephores may be central points in the pattern of vesicular traffic in the cell. PMID- 2877508 TI - Effect of a selective thrombin inhibitor MCI-9038 on fibrinolysis in vitro and in vivo. AB - The effect of a selective thrombin inhibitor, (2R, 4R)-4-methyl-1-[N2-[(3-methyl 1,2,3,4-tetrahydro-8-quinolinyl)sulfonyl]- L-arginyl]-2-piperidinecarboxylic acid (MCI-9038), on the fibrinolysis induced by t-PA and u-PA was studied in vitro and in vivo. MCI-9038 remarkably reduced the lysis time of the plasma clot generated by the addition of calcium chloride to the plasma at the concentration ranging from 0.01 to 0.3 microM. Heparin also reduced the plasma clot lysis time with a lower effect than MCI-9038. The fibrin crosslinkage in the plasma clot was inhibited by MCI-9038 or heparin. MCI-9038 potently inhibited the factor XIIIa generation from factor XIII by thrombin. The effect on the in vivo thrombolysis was studied on the arterial thrombosis generated by the endothelial cell injury of the rabbit carotid artery by acetic acid. t-PA dissolved the thrombi with the infusion at 0.96 mg/kg over 2 h without a significant activation of a systemic fibrinolysis. u-PA dissolved the thrombi with the infusion at 180,000 and 360,000 IU/kg over 2 h. At a dose of 0.48 mg/kg t-PA or 90,000 IU/kg u-PA, the thrombi were not dissolved, but the combined use of MCI-9038 at 1.2 mg/kg over 2 h effectively dissolved the thrombi. Thus, combination of MCI-9038 with plasminogen activators accelerated thrombolysis of an experimental thrombosis in rabbits. PMID- 2877510 TI - Inhibitory effects of rimorphin and dynorphin on insulin secretion from the isolated, perfused rat pancreas. AB - In order to settle the question about whether or not opioid peptides stimulate or inhibit insulin secretion, we studied effects of rimorphin and dynorphin, two members of the preproenkephalin B group, on glucose-induced insulin secretion in the isolated, perfused rat pancreas. These peptides (3.95 X 10(-8) M), like morphine (3.95 X 10(-8) M), significantly inhibited the glucose-induced insulin secretion. The inhibitory effect of rimorphin was attenuated by naloxone (1.2 X 10(-6) M) and phentolamine (10(-6) M), suggesting an involvement of adrenergic alpha receptors in the inhibition of glucose-induced insulin secretion mediated through specific opiate receptors. Rimorphin also inhibited glucose-induced insulin secretion even in the cysteamine-treated rat pancreas from which somatostatin had been depleted. Thus, somatostatin does not appear to play a major regulatory role in the insulin secretion in the pancreas. PMID- 2877511 TI - Di-n-octyl phthalate (DOP), a relatively ineffective peroxisome inducing straight chain isomer of the environmental contaminant di(2-ethylhexyl)phthalate (DEHP), enhances the development of putative preneoplastic lesions in rat liver. AB - Di-n-octyl phthalate (DOP) is the straight chain isomer of di(2-ethylhexyl) phthalate (DEHP) which is a widely used plasticizer and an environmental contaminant. DEHP is a strong inducer of peroxisome proliferation in rat liver. This is significant since other compounds which are strong inducers of peroxisome proliferation have been reported to be weak carcinogens (Reddy, J.K. and Lalwani, N.D., CRC Crit. Rev. Toxicol., 12 (1983) 1). In contrast to DEHP, DOP causes little or no induction of liver peroxisomes (Mann, A.H. et al., Toxicol. Appl. Pharmacol., 77 (1985) 116, and Gray, T.J.B. et al., Toxicology, 28 (1983) 167). In the current study the ability of 1% DOP to promote the development of putative preneoplastic lesions was evaluated. The effect of feeding 0.5% DEHP as well as equimolar amounts of its 2 major metabolites, mono(2-ethylhexyl)phthalate (MEHP) and 2-ethylhexanol (2-EH) were also investigated. GGT+ foci were initiated in the livers of Sprague--Dawley male rats with a single dose of diethylnitrosamine (DEN) following partial hepatectomy. The control group of rats was fed a semipurified diet (Co) for 10 weeks while the experimental groups received the semipurified diet containing the respective compounds. Induction of peroxisome proliferation was monitored by carnitine acetyltransferase (CAT) levels. DOP treatment resulted in a 6-fold increase in the number of GGT+ foci (20.8 +/- 4.0 vs. 3.5 +/- 1.3; P less than 0.05). This was accompanied by no change in liver weight and only a slight increase in CAT activity when compared with control animals. In contrast to DOP, 2-EH produced essentially no effect with regard to number of foci, peroxisome proliferation or liver weight. DEHP and MEHP induced significant peroxisome proliferation and hepatomegaly but the number of foci were significantly lower than in 2-EH-treated rats. The mechanism for the promoting ability of DOP is not clear but would not appear to be related to peroxisome proliferation. Because of the close similarity of chemical structure and metabolism between DOP and DEHP, it is possible that studies to define the mechanism of DOP induced promotion might also serve to further clarify the mechanism of DEHP induced carcinogenesis. PMID- 2877513 TI - Anomalies in sea-urchin egg development induced by a novel purine isolated from the sea-anemone Bunodosoma caissarum. AB - Caissarone (mol. wt 229.5; melting point 285-290 degrees C) is a novel purine isolated and purified from the sea-anemone Bunodosoma caissarum. The purine inhibits the detachment of the vitelline layer from the sea-urchin egg plasma membrane after fertilization and this effect leads to polyspermy. Various abnormalities were detected at various embryonic stages, from multipolar egg division through unequal cleavages and exogastrulation up to teratogenic effects on the sea-urchin larvae (echinopluteus). PMID- 2877512 TI - Effects of intra- and extracellularly applied phospholipases C on excitability of squid giant axons. AB - The effects of phospholipases C on the membrane excitability of the squid giant axon were investigated using phosphatidylcholine-hydrolyzing phospholipase C and sphingomyelinase C of Bacillus cereus, and phosphatidylinositol-specific phospholipase C of Bacillus thuringiensis. When the squid axon was perfused internally with phosphatidylcholine-hydrolyzing phospholipase C in KF or K glutamate solution, the action potential was blocked in 4-7 min and membrane resistance decreased with time to a level less than one-tenth that of control. These effects were irreversible. When the axon was perfused internally with sphingomyelinase C in KF solution, the action potential was decreased to 30% in 3 min. Perfusion with enzyme-free KF solution fully restored the action potential. When the axon was perfused internally with phosphatidylinositol-specific phospholipase C in K - glutamate solution, the action potential was gradually decreased and blocked after 10 min. Perfusion with enzyme-free KF solution restored the action potential by 70%. When phosphatidylcholine-hydrolyzing phospholipase C was applied externally to the squid axon, the action potential and the membrane resistance were slowly but irreversibly decreased. These results suggest that membrane phospholipids, such as phosphatidylcholine and phosphatidylinositol, may be associated with the excitability of the membrane of the squid axon. PMID- 2877514 TI - Clostridium perfringens iota toxin: synergism between two proteins. AB - The iota toxin of Clostridium perfringens type E is a guinea pig dermonecrotic, mouse lethal toxin which cross-reacts with the iota-like toxin of Clostridium spiroforme. Antiserum raised against C. spiroforme or C. perfringens type E neutralizes the toxin from both species. By using C. spiroforme antiserum and crossed immunoelectrophoresis, we have found that there are two cross-reacting proteins, designated iota a (ia) and iota b (ib) in the culture filtrate of C. perfringens type E. Both proteins of C. perfringens were separated by preparative isoelectric focusing and had very little toxic activity when tested alone. However, when they were recombined there were 8- and 25-fold increases in bioactivity as determined by mouse lethal and guinea pig dermonecrotic assays, respectively. These results demonstrate that the iota toxin of C. perfringens requires two immunologically and biochemically different proteins for maximum activity. PMID- 2877515 TI - [Metal-ceramics for the improvement of prosthetic treatment in the GDR. 11. Soldering alloy for Gisadent NCA]. PMID- 2877516 TI - [Medical emergencies caused by neuroleptic therapy]. PMID- 2877517 TI - Pathogenesis of urinary tract infections. Bacterial adherence, bladder defense mechanisms. AB - Bacterial virulence depends upon the ability of bacteria to adhere to mucosal cells. The risk of infection is increased by bacterial factors promoting this adherence and the fact that bacterial surface structures seek epithelial receptors. The host's ability to inactivate bacterial virulence factors and to "mask" its own cell receptors determines whether infections are to be warded off successfully. The current knowledge of these processes is reviewed in this article. PMID- 2877518 TI - Control of an outbreak of wet-tail in a closed colony of hamster (Mesocricetus auratus). PMID- 2877519 TI - Treatment of canine colitis. PMID- 2877520 TI - Old vs fresh syrup of ipecac. PMID- 2877522 TI - Single amino acid substitution, from Glu1025 to Asp, of the fps oncogenic protein causes temperature sensitivity in transformation and kinase activity. AB - We have sequenced 2.7 kilobases of v-fps DNA encoding the transforming protein, p140, of the temperature-sensitive (ts) FL-15 clone of avian Fujinami sarcoma virus. Ten single nucleotide differences were found when compared with the v-fps sequence of the temperature-resistant (tr) clone, FSV-2. Of these differences, five encoded altered amino acids within the 5' fps domain, only one encoded an altered amino acid in the 3' kinase domain, and four were silent. Among the five amino acid changes in the 5' fps domain, four were identical to the corresponding residues of c-fps, and the remaining one, a change from His to Arg at amino acid number 559, was located in the middle of a stretch of five consecutive histidine residues. These sequence comparisons suggested that only two amino acid changes, His to Arg at amino acid 559 and Glu to Asp at amino acid 1025, were likely to be responsible for the temperature sensitivity of the v-fps protein. Two recombinants, pFL-11 containing the 5' alterations and pFL-12 containing the single 3' mutation, were constructed in vitro to determine the precise ts lesion. It was found that both the recombinant pFL-12 and the parental pFL-5 were ts by three criteria: cell morphology, colony formation, and kinase activity. In contrast, the recombinant pFL-11 was ts in morphology, but not in colony formation, and was partially ts in kinase activity. pFSV 2-2 itself was temperature resistant by these criteria. We conclude that, first, the mutation of Glu to Asp at amino acid number 1025 can cause a complete ts phenotype, implying that this residue is located at a critical position of the v-fps oncogenic protein. Secondly, the change from His to Arg at amino acid position 559 results in a partial temperature sensitivity, providing the genetic evidence for a second functional domain of the v-fps oncogenic protein. PMID- 2877521 TI - Isolation of piliated Escherichia coli from diarrheic foals. AB - Escherichia coli was isolated from the feces and intestines of foals with and without diarrhea. Piliation of isolates was demonstrated by electron microscopy and agglutination in antisera having specificity for K88, K99, P987 and F41 pili. Piliation was also demonstrated by electron microscopy on organisms which did not react with any of the antisera. PMID- 2877524 TI - [Use of neuroleptics in treating alcoholism patients]. PMID- 2877525 TI - [Mechanism of action of beta-adrenoblockaders in ischemic heart disease]. PMID- 2877523 TI - [Changes in hormonal-mediatory and immunological indices during anesthesia in cancer patients]. AB - The relationship between hormone-mediator and immunologic components of homeostasis was studied in 82 surgically-treated cancer patients. The pattern of changes in immunity and non-specific resistance was found to depend on the rate of glucocorticoid hormones synthesis in adrenals. Surgery should be carried out under neurovegetative blockade, which prevents immunodepression both during and shortly after surgery. PMID- 2877526 TI - [Therapeutic procedures in gastroesophageal reflux disease]. AB - The medical therapy of reflux esophagitis consists of modifications of the patients's lifestyle and antacids, alginic acid or both (phase I). Phase II medications include drugs that suppress acid/peptic activity (antacid/alginate, H2-receptor blockers, cimetidine, ranitidine, famotidine), drugs that enhance motility (metoclopramide, domperidone) and drugs that coat and increase mucosal protection (sucralfate). Combinations of H2-receptor blockers and motility stimulating drugs have not been very effective. Overall the results of medical therapy of reflux esophagitis are suboptimal. PMID- 2877527 TI - [Adhesins of enteropathogenic bacteria]. PMID- 2877528 TI - [Surgical experiences with segmental pancreatic transplantation in type I diabetes]. PMID- 2877530 TI - [The anxious patient: prevention and therapy concepts for dental practice]. PMID- 2877529 TI - [Association between uptake to lymphocytes from schizophrenic patients and therapeutic efficacy]. AB - Using Le Fur's methods, 3H-spiperone binding was measured in lymphocytes from normal control persons. Although the haloperidol displaceable component of 3H spiperone binding was present in intact lymphocytes, 3H-spiperone binding was not saturable over a wide range of ligand concentrations. It is suggested that this binding is associated with the degree of 3H-spiperone concentration transported into the lymphocytes. 3H-spiperone uptake to lymphocytes in schizophrenic patients (n = 10, including for chlorpromazine responders) and in normal control persons (n = 10) was measured. The 3H-spiperone uptake of schizophrenic patients was significantly higher than that of normal control persons. Especially in three out of the four chlorpromazine responders, 3H-spiperone uptake was much higher than in the rest of the schizophrenic patients. 3H-spiperone uptake of schizophrenic patients was independent of the daily medicational dosages. The 3H spiperone uptake to the lymphocytes in schizophrenic patients seemed to be related to the therapeutic efficacy of the neuroleptics. PMID- 2877531 TI - [Structure of the anxious-delusional syndrome of schizophrenic patients during treatment with anxiolytics]. AB - To study a correlation between anxiety and delirium, 50 schizophrenic patients with the anxiety-delirious syndrome were treated with anxiolytics (leponex and phenazepam). The results were evaluated with the help of a special graded scale. The first control group consisted of 20 patients with vascular and organic psychoses with the anxiety-delirious syndrome who were treated by phenazepam. The second control group was composed of 20 schizophrenics with analogous symptomatology treated by traditional neuroleptics (haloperidol and tisercin). In many patients reduction of anxiety closely and directly correlated with that of delirium, which evidenced the leading role of anxiety in the structure of the syndrome in those patients. It has been demonstrated that in patients of this group treatment with antianxiety drugs is more effective than that with conventional neuroleptics. The diazepam test is proposed as a method of predicting the effect of anxiolytic therapy. PMID- 2877532 TI - [Clinical picture and changes in the activity of several cerebrospinal fluid enzymes in stroke]. AB - Having studied the clinical picture and changes in the activity of various enzymes in the cerebrospinal fluid (CSF) in 140 patients with cerebral strokes, the authors showed a diagnostic and prognostic value of determining the activity of LDH and GGTP in the CSF. The activity of these enzymes increased in hemorrhagic stroke and in cases of unfavourable outcome. Their activity was lower in ischemic stroke and in cases of a favourable course of the disease. PMID- 2877534 TI - The control of catch-up growth. AB - Catch-up (compensatory) growth following transient growth retardation due to illness or starvation has long been recognized in biology and in clinical medicine. This report summarizes work utilizing experimental models in rats in efforts to elucidate the control of catch-up growth. The results support the hypothesis that the catch-up growth mechanism includes a set-point or reference for body size appropriate for age and that the control resides in the central nervous system. Growth hormone (GH) secretion is increased during catch-up growth, although the results also show that increased GH secretion is not required for catch-up growth acceleration. Environmental light modulates the effect of catch-up growth on GH secretion. The mechanisms for sensing a deficit in body size and for stimulating catch-up growth acceleration remain unknown. PMID- 2877533 TI - Multiple endocrine neoplasia with Cushing's syndrome due to paraganglioma producing corticotropin-releasing factor and adrenocorticotropin. AB - A male patient with corticotropin-releasing factor (CRF) and adrenocorticotropin (ACTH)-producing syndrome is described. Soon after being referred to us the patient developed pneumonia, anaemia, oedema and respiratory distress, and died on the 24th day after admission. Autopsy and histology revealed that he had a rare type of multiple endocrine neoplasia (type 1 + paraganglioma) with a mediastinal paraganglioma, parathyroidal hyperplasia, pancreatic islet cell adenoma, duodenal multiple carcinoid tumours and adrenocortical nodular hyperplasia. It was not possible to examine the pituitary. The paraganglioma contained a large amount of immunoreactive (IR)-CRF (606 ng/g wet weight), IR ACTH (59.4 ng/g wet weight), IR-human proopiomelanocortin n-terminal (1-76) peptide (hNT, 156.8 ng/g wet weight) and IR-beta-lipotropin (beta-LPH, 146.9 ng/g wet weight). The major IR-ACTH, beta-LPH and IR-hNT were eluted at ACTH-(1-39), beta-LPH and hNT marker positions, respectively. Big ACTH was not detected. IR CRF eluted at the human CRF marker position on Sephadex G-75 chromatography and high performance liquid chromatography (HPLC). The IR-CRF fraction from the HPLC showed CRF bioactivity which paralleled that of synthetic human CRF in monolayer cultured rat anterior pituitary cells. Our results suggest that not only ACTH but CRF produced by the paraganglioma was responsible for the patient's Cushing's syndrome. PMID- 2877535 TI - The effects of intranasal insufflation of growth hormone releasing factor analogue GRF 1-29 NH2 on growth hormone secretion in children with short stature. AB - The effects of intranasal insufflation of the synthetic growth hormone releasing factor GRF 1-29-NH2 on serum growth hormone (GH) were investigated in five healthy prepubertal children with short stature. 100 micrograms/kg/body weight of synthetic GRF 1-29-NH2, 500 micrograms in 100 microliters water, were insufflated intranasally after careful cleaning of the nose. GRF 1-29-NH2 induced a prompt rise of serum GH levels with peak values at 15 minutes in all children investigated. Peak serum GH values were 28.3 +/- 12.0 ng/ml (mean +/- SD), range 17.1 - 47.6 ng/ml; delta GH was 27.0 +/- 12.2 ng/ml (mean +/- SD). Serum GH levels were still significantly raised 120 minutes after the insufflation of GRF 1-29-NH2 (p less than 0.05). No side effects, except for burning of the nasal mucosa in one patient, were observed. The results of this study demonstrate that intranasal insufflation of synthetic GRF 1-29-NH2 induces a prompt release of GH in otherwise normal children with short stature. Pulsatile intranasal insufflation of GRF 1-29-NH2 probably could be used for the treatment of some children with GH deficiency due to a defect at a suprapituitary level. PMID- 2877536 TI - Normalization of glucose homeostasis by a long-acting somatostatin analog SMS 201 995 in a newborn with nesidioblastosis. AB - A female child was admitted to the hospital few days after birth with severe hypoglycemia and convulsive episodes. Plasma insulin levels were elevated and oral and intravenous administration of glucose were unable to keep blood glucose above 2 mmol/l limit. Intravenous infusion of a long acting somatostatin analog, SMS 201-995, at a dosage gradually increasing from 2 to 50 micrograms/24 hr, was accompanied by a dramatic fall in circulating insulin levels. Normality of glucose homeostasis was restored and convulsive spells ceased. Fasting blood glucose levels stabilized between 3.4 and 4.7 mmol/l. No rebound phenomenon was observed during short term interruptions of the SMS 201-995 infusion. A subtotal pancreatectomy was performed during SMS treatment, and the diagnosis of nesidioblastosis was confirmed by immunocytologic and electron-microscopic studies. It is concluded that this new potent and long acting somatostatin derivative may be useful in the management of hyperinsulinism in the neonate. PMID- 2877537 TI - Carbamazepine lowering effect on CSF somatostatin-like immunoreactivity in temporal lobe epileptics. AB - The effect of carbamazepine treatment on CSF-somatostatin-like immunoreactivity (SLI) in patients suffering from temporal lobe epilepsy was investigated. A baseline lumbar puncture was performed on 12 patients and 10 normal volunteers. A second tap was repeated only in patients when they were on peak of carbamazepine concentration for 10 days. Levels of CSF-SLI were measured by RIA. No significant differences were found in CSF-SLI basal concentrations between epileptics and controls, whereas a significant decrease (p less than .0002 Duncan's multiple range test) of CSF peptide levels occurred in 9 of 12 patients under medication. Although the neural mechanism through which carbamazepine lowers CSF-SLI is still unknown, the results of the present study suggest that the reported effect might be part of the apparatus by which carbamazepine exerts its anticonvulsant action. PMID- 2877538 TI - Observations, reflections and speculations on the cerebral determinants of mood and on the bilaterally asymmetrical distributions of the major neurotransmitter systems. PMID- 2877539 TI - Development of tolerance to glyceryl trinitrate in an isolated human peripheral vein and its relation to cyclic GMP metabolism. AB - Human peripheral vein (v. saphena magna) was exposed in vitro to glyceryl trinitrate (GTN) 0.1 mM for 1 h. The subsequent relaxant effect of GTN (10nM-0.1 mM) on vessels contracted by serotonin (0.25 microM) was significantly reduced on vessels preexposed to GTN as compared to control vessels, indicating a development of partial tolerance as far as the vascular smooth muscle relaxant effect is concerned. The impaired relaxant effect was paralleled by a reduced increment of intracellular cyclic GMP. This is, in turn, probably a consequence of both a diminished guanylate cyclase activity and an elevated phosphodiesterase activity in the GTN-tolerant vessels. The relaxant activity as well as the level of intracellular cyclic GMP were restored in GTN-tolerant vessels by dipyridamole (5 microM), an agent with phosphodiesterase inhibiting properties. PMID- 2877540 TI - Dose-response relations in the nephrotoxic action of mercury based on "spot urine" samples. PMID- 2877541 TI - Contractile effects of noradrenaline and 5-hydroxytryptamine in human hand veins: a pharmacological receptor characterization. AB - The postjunctional receptors mediating contractile responses to noradrenaline (NA) and 5-hydroxytryptamine (5-HT) were characterized in ring segments of human hand veins by using subtype selective agonists and antagonists. The mechanical characteristics of the preparations were also examined by length-tension measurements. The length-active wall tension curve was bell-shaped and reached a maximum at a length corresponding to a passive distending pressure of approximately 14 mmHg. (-)-Phenylephrine consistently contracted the veins and was 24 times less potent than (+/-)-NA whereas clonidine produced a contraction in only two out of 11 vessel segments. Neither prazosin nor rauwolscine competitively inhibited the contractile response to NA, and large inter individual differences were found in the degree of inhibition produced by the antagonists. However, application of both prazosin and rauwolscine almost abolished the NA-induced contraction. Ketanserin and methergoline inhibited the contractile response to 5-HT; the former in an apparently competitive manner with a pA2 value of 8.94, whereas the latter substantially reduced the maximum 5-HT response. It is suggested that NA elicits contraction in human hand veins by acting at a mixed population of alpha 1- and alpha 2-adrenoreceptors. The contractile response to 5-HT, on the other hand, appears to be mediated predominantly by 5-HT2 receptors. PMID- 2877542 TI - Alpha-adrenoceptors in the vessels of human finger skin. AB - To characterize alpha-adrenoceptors in the blood vessels of finger skin the effects of selective alpha-1 and alpha-2 adrenoceptor agonists and antagonists on skin blood flow were studied in vivo. The vasoactive substances were administered into the skin by iontophoresis and the effects on blood flow were evaluated with a laser-doppler. After blockade of alpha-1 adrenoceptors with doxazosine, the blood flow reduction induced by the alpha-1 selective agonist, phenylephrine, was diminished but not that caused by the alpha-2 selective agonist, B-HT 933. In contrast, after alpha-2 selective blockade by rauwolscine, phenylephrine but not B-HT 933 caused a marked decrease in blood flow. The results are compatible with the concept that postjunctional alpha-adrenoceptors in human finger skin vessels are of both alpha-1 and alpha-2 subtypes. PMID- 2877543 TI - The comparison of the influence of the central cholinergic system on the catalepsy induced by neuroleptics or opioids. PMID- 2877544 TI - Dexamethasone suppression test in schizophrenic patients before and during neuroleptic treatment. AB - The dexamethasone suppression test (DST) was performed in 21 drug-free schizophrenic patients. The patients satisfied DSM-III and Research Diagnostic Criteria for schizophrenia and were in an acute phase of the disease. In 15 of the patients the DST was repeated after about 5 weeks of treatment with neuroleptics. DST compliance was checked by analysis of dexamethasone concentrations in plasma. In the acute phase 71% (at 04 p.m.) of the patients were nonsuppressors. After neuroleptic treatment the frequency of abnormal responders had decreased to 20%. The decrease in nonsuppressors was not due to alteration of the dexamethasone concentration between the two test occasions. Prolactin levels were markedly increased at the second test occasion compared with the first. There were no significant relationships between cortisol levels, cortisol suppression and prolactin levels. The high frequency of nonsuppressors among schizophrenic patients in the acute phase of the disease indicates that acute stress may be a confounding factor in the outcome of DST. PMID- 2877545 TI - Up-to-date treatment of the patient with hypergastrinemia. PMID- 2877546 TI - Specificity of human immunodeficiency virus (LAV/HTLV-III)-reactive antibodies in African sera from southeastern Tanzania. AB - The prevalence of antibodies to human immunodeficiency virus (HIV = LAV/HTLV-III) in a rural population from the Ifakara area in southeastern Tanzania was investigated. Sera from 286 individuals collected from 1982 to 1984 in connection with a study on liver disorders were tested by an ELISA. Fifty-two (18.2%) of the sera were found positive. While the positives were largely confirmed by one commercial ELISA, they were completely negative by two others. Confirmatory testing by Western blot and competition Western blot showed that the reactivity detected by more sensitive of these assays was largely due to IgG antibodies binding to the HIV core (gag) proteins p17, its precursor p55 and, in some cases, p24. These tests also indicated, however, that the reactive antibodies could not have been elicited by HIV, but possibly by an unknown retrovirus or another cross reactive agent. Thus, by 1984, the area investigated was largely free of HIV infection, but a significant proportion of its population may harbor another retrovirus of unknown pathogenicity. PMID- 2877547 TI - Infectivity to cattle of metacyclic forms of Trypanosoma (Nannomonas) congolense propagated in vitro. I. Development of localized skin reactions following intradermal inoculation. AB - Skin reactions similar to those induced by tsetse infected with Trypanosoma congolense were elicited in cattle at sites of intradermal inoculation of in vitro propagated parasites which morphologically resembled metacyclic trypanosomes. The time to detection of the reaction, the time to maximal size and the maximal size attained were dependent on the number of parasites inoculated, although it was possible to induce a skin reaction with as few as 20 trypanosomes. All cattle became infected with the initial detection of the skin reaction preceding parasitaemia by 3 to 7 days. PMID- 2877548 TI - The affinity of the lectins Ricinus communis and Glycine maxima to carbohydrates on the cell surface of various forms of Trypanosoma cruzi and Trypanosoma rangeli, and the application of these lectins for the identification of T. cruzi in the feces of Rhodnius prolixus. AB - Flagellates of Trypanosoma cruzi (stock Molino 1), obtained from the intestine of experimentally infected Rhodnius prolixus, grown in cellular or acellular culture, as well as from the blood of infected mice, were examined by a direct fluorescence test using the lectins RCA (Ricinus communis-120) and SBA (soy bean agglutinin; Glycine maxima), conjugated with fluorescein isothiocyanate, for the detection of beta-D-galactose and alpha,beta-N-acetyl-D-galactosamine on the membranes of the flagellates. The same reactions were carried out using Trypanosoma rangeli (stock San Agustin), obtained from the intestine, hemo-lymph or salivary glands of experimentally infected R. prolixus, as well as from cultures and from the blood of experimentally infected CFW mice. The results indicate that the membrane of T. rangeli in the salivary glands of the vector contains beta-D-galactose, but that this sugar is absent from all other developmental stages of this trypanosome. All stages of intestinal and cultured. T. cruzi presented positive reactions with RCA-FITC and SBA-FITC. The high specificity of this technique makes it useful for the examination of R. prolixus, previously used in xenodiagnosis of Chagas' disease and for the examination of intradomiciliary or sylvatic vectors in epidemiological surveys in areas where T. cruzi and T. rangeli coexist. Formaldehyde fixed samples can be examined months later and false reports due to T. rangeli can be avoided. PMID- 2877549 TI - Immunization of hamsters with TLCK-killed parasites induces protection against Leishmania infection. AB - Hamsters immunized with N-p-tosyl-L-lysine-chloromethyl ketone TLCK-treated L. brasiliensis brasiliensis (LB) from culture, infected with LB amastigotes presented: a gradual increase in T and B cell responsiveness to mitogens by lymph node lymphocytes, and an increased response to concanavalin A with no changes for dextran sulphate and pokeweed mitogen in splenocytes. Absence of parasites in lymph nodes after 6 weeks post-infection and a nodule 4 times smaller than that of infected control animals. The nodule was undetectable after 70 days of infection. Hamsters preimmunized with TLCK-treated L. donovani (LD) from culture did not show suppression of the blastogenic response to mitogens of spleen and lymph node cells after infection with LD amastigotes and survived for more than one year, whereas infected, unimmunized animals died five months after infection. Animals preimmunized with culture parasites (LB or LD) treated with phenyl-methyl sulphonyl-fluoride (PMSF) and infected with LB or LD amastigotes did not show any protective effect. PMID- 2877550 TI - B lymphocyte population and immunoglobulins in Indian kala-azar in response to chemotherapy. AB - The levels of immunoglobulin classes (IgG, IgM and IgA) along with B lymphocyte population size were estimated in 24 kala-azar (KA) patients and results were compared with those obtained from 30 controls. A marked increase in the level of IgG and to a lesser extent in that of IgM was noted in the sera of KA patients. But, no such difference could be noted in serum IgA level. Along with the increased levels of immunoglobulins the elevation of B lymphocyte population size was also observed. Follow-up studies during and after chemotherapy for the period of 8 months showed that clinical improvement in KA patients resulting from treatment had a positive correlation with the progressive decline in the B lymphocyte population and in the level of immunoglobulin though the latter, particularly IgG, took a longer time to return to normal. PMID- 2877551 TI - Interaction of serum components with the cytotoxic action of Entamoeba histolytica. AB - Native normal human serum is capable of inhibiting the cytotoxic action of Entamoeba histolytica against K562 tissue culture target cells assessed by a 51Cr release test. It is suggested that a part of the inhibitory activity on amoebae's cytotoxic action is represented by the complement system which is known to lyze trophozoites by activation of the alternative pathway. For the rest of the serum's inhibitory activity on amoebic cytotoxic action molecule(s) is (are) responsible which act(s) independently of Mg2+ and Ca2+. The serum components have to act before the trophozoites have come in contact with the target cells. The opsonization of trophozoites with antiamoebic antibodies led to an inhibition of amoebae's cytotoxic action (ACA) in a dose-dependent manner. The inhibitory components of normal human serum and antiamoebic antibodies potentiated each other in their capacity to inhibit ACA. It is suggested that opsonization of amoebae with C3b via its metastable binding site leads to redistribution phenomena on the amoebae's surface similar to the effects observed with antiamoebic antibodies, both events leading to inhibition of ACA. PMID- 2877553 TI - Chemical analysis of compounds extracted from the tergal "spots" of Lutzomyia longipalpis from Brazil. AB - The chemical composition of the compounds contained in the tergal spots of Lutzomyia longipalpis was investigated. Four populations of L. longipalpis were examined, originating from: Sobral, Ceara, Brazil (one spot and two spot populations), Santarem, Para, Brazil (one spot) and Marajo Island, Para, Brazil (one spot). The tergal spots were dissected out, extracted in hexane and analysed on a gas chromatograph/mass spectrometer. Two compounds were found, identical to compounds found in earlier studies, but there was no correlation between number of tergal spots and type of compound present. It was suggested that the number of tergal spots could not be used as a marker for reproductively isolated populations, and that analysis of the compound present within the spots might be necessary to characterize potentially good vector populations. PMID- 2877552 TI - Influence of circulating malarial antigens on cell mediated immunity in acute Plasmodium falciparum malaria. AB - In a group of Thai patients with P. falciparum acute malaria, circulating malarial antigens (CMA) were detected in 27/33 cerebral malaria (CM) cases and 31/43 noncerebral cases. Delayed cutaneous responses to phytohemagglutinin and candidin were found frequently negative in patients with CMA, especially in the CM group. Mean in vitro lymphocyte proliferative responses to lectins were lower in the group of patients with CMA. An inhibitory activity on proliferative responses to phytohemagglutinin of lymphocytes from healthy individuals was exerted by sera containing CMA. Data suggest that CMA from P. falciparum may suppress in vivo and in vitro cell mediated immune reactions. PMID- 2877554 TI - Observations on the distribution of the Anopheles gambiae complex in Tanzania. AB - Adult male and female mosquitoes of the Anopheles gambiae group of species from fourteen localities in Tanzania were studied using either chromosomal inversions, enzyme electrophoresis or both techniques. The 6481 specimens analyzed consisted of 64.4% An. gambiae, 33.6% An. arabiensis, and 2.0% An. merus, but no An. quadriannulatus. An. gambiae and An. merus are reported from Zanzibar for the first time. An. merus was recorded at Buiko, 167 km inland. An. arabiensis is the predominant or exclusive species in dry and semi-arid areas. An. gambiae predominates or is the only species in humid coastal and humid lacustrine areas. PMID- 2877555 TI - Peridomestic breeding sites of Glossina fuscipes fuscipes Newst. in Busoga, Uganda, and epidemiological implications for trypanosomiasis. AB - A search for Glossina fuscipes fuscipes puparia near homesteads in the sleeping sickness focus of Busoga revealed puparia and puparial shells under Coffea canephora (coffee), Musa sp. (banana) and Lantana camara thickets as well as under house verandahs and, once, inside a hut. This is the first description of G.f. fuscipes breeding sites in a peridomestic habitat. The implications of these findings in relation to the transmission of the current epidemic of sleeping sickness in Busoga is discussed. PMID- 2877556 TI - Ascorbic acid induced immune-mediated decrease in mortality in Ichthyophthirius multifiliis infected rainbow-trout (Salmo gairdneri). PMID- 2877557 TI - Comparative evaluation of the El Zogabie modification of the Nytrel urine filtration technique for the detection and enumeration of Schistosoma haematobium ova. PMID- 2877559 TI - Drug therapy for preventing peptic ulcer recurrence. AB - Duodenal ulcers recur in the majority of patients. These patients may be at risk of significant ulcer complications. Risk factors for recurrent ulcers include cigarette smoking and high output of nocturnal acid. Patients at high risk of recurrence are candidates for continuous maintenance therapy. The H2 receptor antagonists and sucralfate are effective in reducing recurrence rates. PMID- 2877558 TI - Delayed type hypersensitivity induced by LPF from Bordetella pertussis. AB - Lymphocytosis Promoting Factor (LPF) obtained from Bordetella pertussis, has the capacity to induce peripheral lymphocytosis in mice and blastogenesis of human lymphocytes in vitro. When this Factor is injected intracutaneously in animals and in humans, it was shown to induce local inflammatory reactions with histological, morphological and chronological characteristics of delayed hypersensitivity. LPF and conventional microbial antigens were tested intracutaneously in 35 patients with carcinoma undergoing immunotherapy and in 15 normal individuals. The results showed that the cutaneous reactions induced by LPF were similar to those of the conventional antigens routinely used to asses cell-mediated immunity. LPF via intracutaneous route did not show any adverse reactions. Histological studies were carried out in mice receiving intracutaneous injections of LPF. The immunological mechanisms involved in the induction of delayed cutaneous hypersensitivity by LPF are discussed. PMID- 2877560 TI - Dermatologic emergencies. AB - Some skin conditions, such as blistering diseases, guttate and pustular psoriasis, exfoliative erythroderma, reactive erythemas and acute contact dermatitis have an acute onset and require prompt intervention. Acute vesicular or weeping dermatoses are best treated with cool, wet compresses and topical lotions, whereas dry, scaly skin conditions should be treated with hydrating measures and topical ointments. Oral antihistamines and topical and systemic steroids are the mainstays of treatment for these severe dermatoses. PMID- 2877561 TI - Attenuation of exercise training effects in patients taking beta blockers during early cardiac rehabilitation. AB - Cardiorespiratory responses to graded treadmill tests administered 1 month after myocardial infarction or coronary bypass surgery and again after 4 weeks of aerobic training were compared in 24 patients taking beta blockers and 15 control patients. There were no significant differences before training between the groups in age, weight, ventricular ejection fraction, oxygen uptake (Vo2) during the fixed work load (1.7 mph/10% grade), Vo2 at the ventilatory threshold, or Vo2max. After training, Vo2max was significantly increased (p less than 0.05) by 16% in the beta-blocker group and by 21% in controls. However, the group taking beta blockers showed no significant change in oxygen pulse (Vo2/heart rate) at the fixed work load or at the ventilatory threshold, whereas the controls increased Vo2/heart rate at the fixed work load by 9% (p less than 0.05) and at the ventilatory threshold by 22% (p less than 0.05). Metabolic and ventilatory responses to submaximal exercise should therefore also be considered when evaluating the efficacy of exercise training in patients taking beta blockers. PMID- 2877562 TI - Beta blockade and chest pain in acute myocardial infarction. PMID- 2877564 TI - Antianginal efficacy of carvedilol, a beta-blocking drug with vasodilating activity. AB - The efficacy of carvedilol, a new vasodilating beta-blocking drug, was evaluated in 20 patients with chronic angina using a single-blind, placebo-controlled protocol. A 2-week placebo phase was followed by therapy with carvedilol, 25 mg twice daily for 2 weeks, after which the dose was doubled. There was then a second placebo phase lasting 2 weeks. Treadmill exercise testing, 24-hour ambulatory electrocardiographic monitoring and drug blood level assays were performed at the end of each phase. Exercise time (mean +/- standard error of mean) increased from 7.4 +/- 0.5 minutes during placebo to 9.0 +/- 0.5 minutes carvedilol, 25 mg twice daily (p less than 0.001), and to 9.2 +/- 0.4 minutes with 50 mg twice daily (p less than 0.001). Mean time to 1 mm of ST depression in both bipolar leads CM5 and CC5 increased significantly, but peak ST depression did not change. Heart rate at rest was reduced at both dose levels, from 86 +/- 4 beats/min during placebo to 70 +/- 2 beats/min with 25 mg twice daily (p less than 0.001) and to 67 +/- 3 beats/min with 50 mg twice daily (p less than 0.001). Systolic blood pressure at rest was significantly reduced at both doses (p less than 0.05; p less than 0.01), but blood pressure during exercise was decreased only with the larger dose (p less than 0.001). The exercise rate-pressure product was 182 +/- 9 with placebo and decreased to 153 +/- 5 with 25 mg twice daily (p less than 0.001) and to 138 +/- 6 with 50 mg twice daily (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877563 TI - Safety and efficacy of flestolol, a new ultrashort-acting beta-adrenergic blocking agent, for supraventricular tachyarrhythmias. AB - Flestolol, a new ultrashort-acting (half-life 6.9 minutes) beta-blocking drug, was administered by intravenous infusion to 18 patients with new-onset atrial fibrillation or flutter and rapid ventricular response (120 beats/min or more for at least 30 minutes). Drug dose of flestolol was progressively increased until at least 1 of 3 endpoints was achieved: at least a 20% reduction in heart rate from baseline, heart rate 100 beats/min or less, or conversion to normal sinus rhythm. Flestolol was then administered as a maintenance infusion up to 24 hours. When flestolol was discontinued, patients were monitored for 1 additional hour. The mean ventricular response at baseline of 133 +/- 12 beats/min decreased to 103 +/ 20 beats/min at the end of flestolol titration (p less than 0.0001). Fourteen patients (78%) achieved defined endpoints. All 14 patients who continued to receive maintenance infusion had a sustained response. When flestolol was discontinued, ventricular response increased 33 +/- 23% within 60 minutes. The only adverse effect seen was hypotension in 2 patients. Flestolol is effective in slowing ventricular response in new-onset atrial fibrillation and flutter, maintains a therapeutic effect during continuous infusion and rapidly loses therapeutic effect when discontinued. PMID- 2877566 TI - Duodenal gangliocytic paraganglioma. Clinicopathologic and immunocytochemical study of 11 cases. AB - The clinicopathologic features of 11 cases (8 in men) of duodenal gangliocytic paraganglioma are presented. The patients averaged 56 years of age; none showed evidence of phakomatosis. Ten tumors occurred in the second portion of the duodenum, and one arose in the third portion. All tumors were polypoid, and half presented with gastrointestinal bleeding. The neoplasms were composed of paraganglioma and carcinoid-like elements, neurons, and Schwann as well as sustentacular cells. All tumors behaved in a benign fashion after local resection or snare polypectomy; long-term follow-up (1-25 years; mean, 8.3 years) showed no recurrence in any case. Immunocytochemical examination demonstrated the presence of somatostatin, serotonin, and human pancreatic polypeptide within endocrine cells and neurons. PMID- 2877567 TI - Famotidine: clinical applications of a new H2-receptor antagonist. Introduction. PMID- 2877565 TI - Control of myocardial tissue components and cardiocyte organelles in pressure overload hypertrophy of the cat right ventricle. AB - Previous studies have demonstrated that there is a disproportionate increase in connective tissue in right ventricular myocardium subjected to pressure-overload hypertrophy associated with depressed cardiac contractility. While the myocardium is primarily responsive to load, the aim of the present study was to determine whether catecholamines also modulate the response of myocardial tissue components and cardiocyte organelles in pressure-overload-induced cardiac hypertrophy. Four experimental groups of cats were examined: a sham-operated control group, a group which had their pulmonary arteries banded in order to induce a pressure overload, a group which had been subjected to the same pressure overload, but in addition had beta-adrenoceptor blockade produced prior to and during the pressure overloading, and a group which had been subjected to the same pressure overload, but in addition had alpha-adrenoceptor blockade produced prior to and maintained during the pressure overloading. As in our previous study, there was a significant and equivalent degree of right ventricular hypertrophy in all experimental groups with pressure overload when assessed either as the ratio of right ventricular weight to body weight or as cardiocyte cross-sectional area. At the light microscopic level, the disproportionate increase in the volume density of myocardial connective tissue seen in banded animals was completely prevented by either alpha- or beta-adrenoceptor blockade. At the electron microscopic level, there was a reduction in the mitochondrial and myofibrillar volume fractions following beta-adrenoceptor blockade. The results of this study provide evidence for a modulatory role of catecholamines in the control of myocardial connective-tissue proliferation in pressure-overload-induced cardiac hypertrophy. There is also evidence to support the role of the adrenergic nervous system in regulating cardiocyte subcellular organelles, independent of the regulation of cardiocyte size. PMID- 2877568 TI - Famotidine: clinical applications of a new H2-receptor antagonist. May 16, 1986, Carmel, California. PMID- 2877569 TI - Treatment of active duodenal ulcers with famotidine. A double-blind comparison with ranitidine. AB - In a double-blind multicenter trial, 100 patients with active duodenal ulcer were treated with a single nocturnal dose of famotidine 40 mg or ranitidine 300 mg. Antacid tablets were allowed as additional treatment if needed for pain relief. Endoscopy was repeated after two weeks, and again after four weeks if the ulcer had not healed earlier. Two patients in the famotidine group were withdrawn from the study because of non-compliance with the protocol. After two weeks, ulcers in 64 percent of the patients receiving famotidine and 46 percent of the patients receiving ranitidine were healed (p = 0.072). After four weeks, healing rates were 94 percent (famotidine) and 90 percent (ranitidine). Pain relief was rapid in either treatment group, with a tendency for better response during the day in the famotidine group. Mean antacid consumption during the first week was 3.0 tablets (34.5 mmol) in the famotidine group and 4.1 tablets (47.2 mmol) in the ranitidine group. Famotidine provides excellent healing and relief of symptoms in patients with duodenal ulcer disease. PMID- 2877570 TI - A multicenter, randomized, double-blind study comparing famotidine with ranitidine in the treatment of active duodenal ulcer disease. AB - Famotidine, a new long-acting histamine (H2)-receptor antagonist, has recently been shown to be more effective than placebo in healing active duodenal ulcer. In the current study, the efficacy and tolerability of famotidine were further investigated and compared with those of ranitidine in a multicenter, double blind, randomized international study. Sixty-eight investigators from 19 countries enrolled 1,031 patients with endoscopically proven active duodenal ulcers. Patients received either ranitidine (150 mg twice daily) or famotidine at one of three different dosage regimens: 40 mg at bedtime, 40 mg twice daily, or 20 mg twice daily. Ulcer healing was assessed by serial endoscopy with pain relief and safety profiles also closely monitored. Nine hundred and eighty patients fulfilled the evaluation criteria. During the eight-week study, there was no significant difference in ulcer healing rates between the ranitidine control group and any of the famotidine treatment groups. At eight weeks, the healing rates were 87, 92, 92, and 90 percent for the famotidine (40 mg at bedtime, 20 mg twice daily, and 40 mg twice daily) and ranitidine groups, respectively. Ulcer pain improved and antacid consumption decreased in all the groups equally. The clinical and safety profiles were also similar in all four groups. This study indicates that famotidine used once or twice a day is as effective and well tolerated as twice-a-day ranitidine in the treatment of active duodenal ulcers, with the recommended dosage being 40 mg at bedtime. Furthermore, these data emphasize the importance of nocturnal acid secretion in the pathophysiology of duodenal ulcer disease. PMID- 2877571 TI - Maintenance therapy of duodenal ulcer with famotidine. A multicenter United States study. AB - The decision to treat a patient with duodenal ulcer should be based upon the following: severity of disease; effectiveness of treatment; and risk and cost of treatment. A number of drugs are effective for this condition. When administration of the drug is discontinued, a recurrence of the ulcer occurs most often within three months, with the rate approaching 90 percent at one year. Maintenance therapy has evolved as a method of preventing recurrence. A double blind, randomized, multicenter study was done to compare 40 mg of famotidine at bedtime, 20 mg of famotidine at bedtime, and placebo in the maintenance treatment of patients with recently healed duodenal ulcer. In 37 centers in the United States, 303 patients received randomly allocated treatment with 40 mg of famotidine at bedtime (107 patients), 20 mg of famotidine at bedtime (97 patients), or placebo (99 patients). The treatment groups were comparable as to the risk factors and other characteristics. Esophagogastroduodenoscopies were scheduled at three, six, and 12 months of treatment. Additional endoscopies could be done at any time if symptoms suggested a relapse. Cumulative relapse rates were significantly lower in the famotidine groups than in the placebo group at all time points (p less than 0.01). The cumulative life-table relapse rates at three, six, and 12 months were 9.2, 20.9, and 24.8 percent for the 40-mg famotidine group; 13.5, 16.1, and 23.3 percent for the 20-mg famotidine group; and 39.3, 51.5, and 56.8 percent for the placebo group. No significant difference between the two famotidine groups was observed. Within each period, the relapse rate was lower with famotidine than with placebo. Famotidine is more effective than placebo as maintenance therapy. It is generally well tolerated for periods of up to one year. A dose of 20 mg at bedtime is proposed as the maintenance dose. Fewer relapses occurred in non-smokers, in females, and in patients in whom healing occurred with placebo. More relapses occurred in patients under 40 years of age, patients with a long ulcer history, or patients who were younger than 40 years of age at onset of ulcer disease. PMID- 2877572 TI - Pharmacodynamics of famotidine in humans. AB - The physiologic role of histamine (H2) receptors and their involvement in pharmacologic responses have not been completely defined. To date, H2-receptor specific pharmacologic actions of H2-receptor inhibitors in humans are primarily associated with effects on gastric acid secretion. Famotidine is a new potent competitive inhibitor of H2 receptors. During its development, in addition to studies defining its gastric acid antisecretory profile, famotidine was also examined for potential effects on other functions of the gastrointestinal tract and on other systems. Famotidine inhibits basal and stimulated gastric acid secretion in a dose-dependent manner after oral administration of 5 to 40 mg. Maximal effect is achieved by the 40-mg dose, with peak activity reached one to three hours after dosing and a duration of action lasting 10 to 12 hours. Gastric emptying times and exocrine pancreatic function are not affected after famotidine (40 mg twice daily) treatment. Blood pressure, heart rate, and electrocardiographic patterns remain unchanged after oral or intravenous administration of famotidine in doses up to 40 mg and 20 mg, respectively. Serum prolactin levels do not rise after intravenous administration of 20 mg of famotidine. The levels of prolactin, testosterone, dehydroepiandrosterone, follicle-stimulating hormone, luteinizing hormone, and other circulating hormones remain unchanged during four weeks of treatment with famotidine 40 mg daily. Renal inulin and creatinine clearances show no change after intravenous administration of 10 mg of famotidine, and tubular excretion of procainamide and its major metabolite is unchanged after administration of 40 mg of famotidine. No significant effects are found on the biologic disposition of theophylline, warfarin, and other compounds metabolized by the liver cytochrome P450 enzyme system when they are given concomitantly with famotidine. PMID- 2877574 TI - Economic and health aspects of peptic ulcer disease and H2-receptor antagonists. AB - The costs of peptic ulcer disease to society are very high. Costs can be expressed as either direct or indirect. Direct costs include hospitalization or clinic visits, physicians' fees, and medication. Indirect costs are loss of productivity due to absenteeism from work or loss of income from death of an employee. The daily cost of different ulcer drugs such as the histamine (H2) receptor antagonists for intravenous treatment, acute healing, and maintenance can easily be compared. As newer anti-ulcer drugs such as H2-receptor antagonists have been introduced into the marketplace, the number of prescriptions and medication costs have increased rather than decreased. In part, this may be accounted for by the high frequency with which H2 antagonists are prescribed for patients with non-ulcer dyspepsia. Some patients have chronic peptic ulcer disease with multiple painful recurrences or complications such as hemorrhage, perforation, or obstruction. They may require long-term care or drug maintenance, hospitalization, or surgery. For patients with chronic ulcer disease or complications, randomized controlled trials to compare the efficacy, safety, and costs of different forms of therapy (maintenance drugs, surgery, or placebo) have not been reported. However, based upon good efficacy and safety for acute healing and long-term drug maintenance for painful duodenal ulcer disease, long-term maintenance with H2-receptor antagonists is now prescribed for many patients. No controlled randomized trials have been reported to document that long-term maintenance with H2-receptor antagonists actually reduces peptic ulcer complications. However, by current cost estimates, long-term H2-receptor antagonist therapy is less expensive than ulcer surgery for uncomplicated ulcer disease for up to eight years. However, maintenance drug therapy after eight years may be more expensive than elective ulcer surgery in patients with chronic peptic ulcer disease who are good surgical candidates. Patients with complications of peptic ulcer disease seem to represent a different subset than patients with symptomatic ulcer disease. Further studies in these subsets are needed to ascertain the most effective, safest, and least expensive management such as surgery, long-term drug maintenance, or intermittent drug therapy to prevent recurrent ulceration or complications.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2877573 TI - Efficacy and safety of famotidine in the management of benign gastric ulcers. AB - The worldwide experience with famotidine in the management of benign gastric ulcers is reviewed. Analysis of data from 15 countries has shown that famotidine is more effective than placebo in treating gastric ulcers. Relief of pain is achieved earlier in famotidine-treated patients. Complete endoscopic healing may be expected in 64 to 80 percent of patients within eight weeks following the initiation of therapy. Response to famotidine does not appear to be affected by age, sex, smoking, regular alcohol consumption, or duration of disease. Short term oral famotidine, at a dose of 40 mg daily, is well tolerated, and there have been no serious adverse experiences attributed to its administration. The efficacy of famotidine is comparable to that of other histamine (H2)-receptor antagonists. PMID- 2877575 TI - Famotidine in the therapy of gastric hypersecretory states. AB - The histamine (H2)-receptor antagonist famotidine was compared with ranitidine and cimetidine in its ability to control gastric acid hypersecretion in 33 patients with gastric hypersecretory states (32 patients with Zollinger-Ellison syndrome and one patient with idiopathic hypersecretion). Equipotent doses of each drug were determined in nine patients and used to determine relative onset of action, duration of action, and potency. Each drug had a similar time course of onset with a maximal effect at three to four hours after oral ingestion. The duration of action of famotidine was 30 percent longer than that of either cimetidine or ranitidine. In terms of relative potency, famotidine was nine times more potent than ranitidine and 32 times more potent than cimetidine. Thirty-two patients underwent long-term famotidine treatment for up to 34 months (mean, 10 months) with a duration in 21 patients of at least six months, in nine patients of at least 12 months, and in six patients of at least 24 months. The mean daily maintenance dose with famotidine was 0.33 g per day (range, 0.05 to 0.8 g). Prior to famotidine therapy, 27 patients were taking ranitidine and the mean daily dose required was 2.3 g per day (range, 0.6 to 5.4 g), whereas six patients were taking cimetidine and the mean daily dose was 4.6 g per day (range, 1.2 to 9.0 g). Fourteen of the 32 patients required an anticholinergic agent in addition to ranitidine or cimetidine to maintain control, whereas only five patients required an anticholinergic agent with famotidine. Gastric acid hypersecretion was controlled in seven patients with less frequent dosing with famotidine than with cimetidine or ranitidine. Long-term treatment with famotidine was not associated with any hematologic or biochemical toxicity or clinical side effects. These results demonstrate that famotidine has a similar onset of action to other H2 receptor antagonists but has a 30 percent longer duration of action and is nine times more potent than ranitidine and 32 times more potent than cimetidine. Famotidine is safe and highly effective in the long-term treatment of gastric hypersecretory states. PMID- 2877576 TI - Comparison of effects of oral and intravenous famotidine on inhibition of nocturnal gastric acid secretion. AB - In this double-blind, placebo-controlled, four-way crossover, randomized study, eight high-secretor (more than 5 meq per hour) volunteers received 20 mg of famotidine by mouth, 10 mg intravenously, and 20 mg intravenously at 9 P.M. Volume, acid content, and pH of continuous gastric aspirates were measured hourly from one to at least 12 hours after treatment. Plasma concentrations of famotidine were determined at specified intervals. All famotidine doses produced marked suppression of gastric secretion. The mean total output was 1,196.3, 526.8, 414.9, and 518.0 ml for placebo, the 10-mg intravenous famotidine dose, the 20-mg intravenous dose, and the 20-mg oral dose, respectively. The latter three values were significantly different from that of placebo at p less than 0.01. The mean total acid output was 105.3, 8.3, 2.3, and 6.2 meq, respectively, and the acid output for all three doses was significantly different from that of placebo at p less than 0.01. The onset of antisecretory effect was noted as early as one hour after dosing. The mean gastric aspirate pH values were 1.7, 5.5, 6.2, and 4.4 during the second hour after placebo, the 10-mg intravenous dose, the 20 mg intravenous dose, and the 20-mg oral dose, respectively, with the treatment pH values significantly different from the placebo pH value at p less than 0.01. Higher mean pH values were reached at seven, eight, and nine hours after the 20 mg intravenous dose than after the 10-mg intravenous dose (p less than 0.05). By the 12th hour after administration of the 10-mg intravenous dose, pH values had returned to baseline in all but one subject. After the 20-mg intravenous dose, a similar loss of effect occurred in one subject at 12 hours and in all subjects by 15 hours. Plasma concentrations of famotidine greater than 50 ng/ml were associated with an acid output inhibition of more than 80 percent, whereas high (more than 90 percent) as well as low (less than 50 percent) inhibition was observed at famotidine concentrations below 50 ng/ml. PMID- 2877577 TI - Famotidine: an appraisal of its mode of action and safety. AB - Famotidine is a potent histamine (H2)-receptor antagonist that binds to the H2 receptor in a competitive reversible manner as shown by in vivo, in vitro, and clinical studies. Famotidine has shown no evidence of carcinogenicity, mutagenicity, or teratogenicity in extensive and adequately designed safety assessment studies. The drug produces neither prolonged anacidity nor doses its use result in significant elevations of serum gastrin levels beyond those seen with other available H2-receptor antagonists when used as recommended for the treatment of ulcer disease. Taken together, these data demonstrate no undue or disproportionate risk to the use of famotidine. PMID- 2877578 TI - Perspectives on treating hypertension. AB - Lowering the blood pressure to levels for which the arterial system has been designed should reduce various complications in the coronary and cerebral arteries, the heart, and the kidney. However, the antihypertensive treatment itself should not produce any significant damage. It is very likely that early modes of antihypertensive treatment did cause some biologic harm, which prevented the expected reduction in the incidence of coronary artery disease. However, the inability of these early forms of treatment to greatly improve coronary artery disease does not necessarily apply to treatments of the future. PMID- 2877579 TI - Natural history of patients with congestive heart failure. Potential role of converting enzyme inhibitors in improving survival. AB - To alter the natural history of congestive heart failure and change the poor prognosis for patients with this condition will require new insights into its pathogenesis as well as the development of strategies to alter the neurohumeral and serum electrolyte abnormalities associated with congestive heart failure, which are often exaggerated by current therapeutic approaches. Although improvement in hemodynamics and exercise tolerance in patients with congestive heart failure remains important, the emphasis of therapeutic goals should be shifted to prevent further cardiac deterioration and to prevent sudden cardiac death. The use of converting enzyme inhibitors holds promise for a beneficial effect on the altered hemodynamic, electrolyte, and neurohumeral abnormalities associated with congestive heart failure. If further prospective randomized trials confirm the beneficial effects of these agents in reducing the mortality rate among patients with congestive heart failure, it is likely that these benefits will have stemmed from their effects on neurohumeral factors and serum electrolyte abnormalities rather than from their effects on hemodynamics. PMID- 2877580 TI - Prune belly syndrome and retroperitoneal germ cell tumor. AB - The prune belly syndrome is a congenital set of anomalies that includes cryptorchidism. Despite the known risk of testicular tumors in cryptorchid testes, what may be the first case of a germ cell tumor complicating the prune belly syndrome is described herein. PMID- 2877581 TI - HTLV-I-associated T-cell leukemia in Hawaii. AB - Adult T-cell leukemia (ATL) is a disease found endemic in Southern Japan and the Caribbean basin. The human T-cell leukemia virus I (HTLV-I) has been implicated epidemiologically as the causative agent in this disease. This paper describes the identification of this disease in Hawaii in a second generation immigrant from Southern Japan. The disease was initially indolent, then clinically explosive, characterized by cutaneous lesions, leukemic lymphocytes with convoluted nuclei of T-cell phenotype, hypercalcemia, and a terminal infection. PMID- 2877582 TI - Molecular detection of carriers of hereditary amyloidosis in a Swedish-American family. AB - Autosomal dominant amyloidosis, also known as familial amyloidotic polyneuropathy (FAP), is a late-onset disorder associated with variants of the protein prealbumin. In FAP Type I, the variant contains a single amino acid substitution at position 30 in the subunit. This substitution corresponds to a single base change in the gene, coincidentally creating a new site for the restriction enzyme NsiI. This change is detectable in the DNA of gene carriers with restriction fragment length polymorphism (RFLP) methods. A well-characterized American family of Swedish origin was studied by this method using a prealbumin cDNA. The RFLP data were found to correlate with previous biochemical characterization of the prealbumin in this family, indicating that this test represents a reliable way to directly detect the DNA mutation responsible for the condition. This test can be used for preclinical diagnosis of gene carriers, including prenatal diagnosis. PMID- 2877583 TI - Effects of cholecystokinin-octapeptide on gastric motility of anesthetized dogs. AB - The present experiments examined the local effects of cholecystokinin-octapeptide (CCK-8) and related peptides on gastric motility of anesthetized dogs. Peptides were injected through the gastroepiploic artery at doses of 1.0, 2.5, 5.0, 10.0, and 20.0 ng/ml. CCK-8 and its analogues (Glt-CCK-8, pGlu-CCK-8, and Suc1-MePhe8 CCK-7) increased gastric smooth muscle contraction in a dose-dependent manner. ED50 of CCK-8 was 2.97 +/- 0.63 ng/ml. Administration of atropine (100-200 micrograms/kg) inhibited the effects of both CCK-8 and pentagastrin; however, hexamethonium (5 mg/kg) failed to block the contractile response induced by CCK-8 and pentagastrin. These results indicate that CCK-8 and related peptides can act as local modulators in controlling the neural regulation of gastric motility. PMID- 2877585 TI - Activation of a cranial vasodilator pathway during seizures in rats. AB - The purpose of this study was to determine whether seizures, which activate sympathetic nerves, also activate a vasodilator pathway to extracranial tissues of the head. Blood flow was measured with microspheres during control conditions and seizures in anesthetized, paralyzed rats. Seizures were produced by bicuculline or pentylenetetrazole. During seizures in rats with intact sympathetic nerves, blood flow to masseter muscle decreased and blood flow to tongue did not change. Following bilateral cervical sympathetic denervation or high spinal cord section, seizure produced marked increases in blood flow to masseter and tongue. These vasodilator responses, which were confined to the cephalic circulation (and were not observed in biceps femoris) were blocked by hexamethonium. The vasodilator response to seizures in masseter and tongue was not significantly attenuated after atropine. Thus seizures activate a dilator pathway to extracranial tissue of the head, sympathetic nerves limit the increase in blood flow produced by activation of the cranial dilator pathway during seizures, and vasodilatation in masseter and tongue during seizures is mediated primarily by a noncholinergic mechanism. PMID- 2877584 TI - Changes in cardiac and hypothalamic noradrenergic activity with taurine in DOCA salt rats. AB - We studied the role of the cardiac and hypothalamic noradrenergic systems in the hypotensive actions of dietary taurine supplementation in deoxycorticosterone acetate (DOCA)-salt rats. The supplementation with 1% taurine could reduce blood pressure when it was given after DOCA-salt hypertension had been established. The taurine supplementation could attenuate the increased depressor response to hexamethonium-induced ganglion blockade in the DOCA-salt rats. Moreover, noradrenergic activity was determined from the rate of decline of tissue norepinephrine (NE) concentration after the administration of alpha-methyl-p tyrosine. At 23 degrees C, cardiac NE turnover was markedly accelerated in DOCA salt rats compared with the vehicle-injected control rats, but the 1% taurine supplement restored it toward normal. In contrast, turnover time in the hypothalamus was delayed in the DOCA-salt rats compared with the control rats, whereas 1% taurine supplement normalized the hypothalamic NE turnover. Stimulation of sympathetic discharge by cold exposure (4 degrees C, 6 h) after the administration of alpha-methyl-p-tyrosine produced marked depletion of NE in most tissues. The NE deficit in both the hypothalamus and heart was significantly greater in the DOCA-salt rats than in the control rats, but the 1% taurine supplement could normalize this. Thus taurine loading could not only diminish the sympathetic overactivity under the normal condition but also attenuate the augmented hypothalamic and cardiac noradrenergic activity by cold stress in the DOCA-salt hypertensive rats. Evidence presented suggests, therefore, that the hypothalamic noradrenergic system might be involved in the hypotensive action of taurine in DOCA-salt rats. PMID- 2877586 TI - The Pisa syndrome during maintenance antipsychotic therapy. PMID- 2877588 TI - Rapid shifts in therapeutic and extrapyramidal effects of neuroleptics. PMID- 2877587 TI - Alprazolam-neuroleptic combination in schizophrenia. PMID- 2877590 TI - Vecuronium and atracurium infusions during hypothermic cardiopulmonary bypass. AB - Two similar groups of patients undergoing coronary artery bypass grafting received either atracurium or vecuronium infusions for neuromuscular blockade. Both groups demonstrated a marked reduction in neuromuscular blocking requirements during hypothermic bypass at 30 C. The ratio of the dose rates at 30 C to that at 37 C was significantly less with vecuronium (p less than 0.01). PMID- 2877589 TI - Lymphocyte subsets in habitual abortion. AB - Lymphocyte subpopulations were characterized by means of monoclonal antibodies in 25 women with habitual abortion and 21 multiparous normal women. Compared to nonpregnant women (N = 8), pregnant normal women were associated with significantly lower helper-to-suppressor ratios (1.71 +/- 0.41 versus 2.37 +/- 0.66). In contrast in pregnant women with habitual abortion (N = 13) the ratio remained high (2.32 +/- 0.73). Failure to increase the number of suppressors and a significant rise in helpers caused this increased ratio. We discuss the possible mechanisms and etiological importance of this finding in habitual abortion. PMID- 2877591 TI - Bronchospasm following the use of vecuronium. AB - A case history is presented which records bronchospasm due to vecuronium. Immunological investigations, including basophil degranulation tests, indicated that the bronchospasm was not caused by direct histamine release and was not IgE mediated. It was of interest that intradermal testing gave a positive wheal response against neuromuscular agents other than those involved in the anaesthetic procedure under investigation. A positive reaction to vecuronium was only obtained when given in a high concentration and accords with the general belief that vecuronium has extremely low potential for histamine release. PMID- 2877593 TI - [Rapid onset of the action of vecuronium by administration of a precurarizing dose]. AB - The administration of vecuronium in divided doses with respect to onset of action and intubating conditions was investigated. This study was conducted in 3 parts. In part 1 the maximal precurarizing dose of 0.015 mg/kg vecuronium was found. In the second part we showed that the optimal time interval between divided doses was 3 min. In the third part we made a comparative investigation between the effect of 0.015 + 0.085 mg/kg body wt. at a 3 min interval and that of a single dose of 0.1 mg/kg body wt. vecuronium. --Neuromuscular function was assessed in semiquantitative manner, using the train of four (TOF) stimulation of ulnar nerve. Administration of vecuronium in divided doses, compared with a single dose of 0.1 mg/kg body wt., resulted in a more than 1 min earlier onset time of 1.5 2.5 min and facilitated early intubation. As soon as twitch tension had completely disappeared uniform by excellent intubating conditions were available in all cases. The administration of vecuronium in divided doses enabled better intubating conditions than the same single dose of vecuronium. PMID- 2877592 TI - In pursuit of relaxation. PMID- 2877594 TI - [Vecuronium in crash intubation]. AB - A prospective controlled study was conducted to compare the efficacy of vecuronium and succinylcholine for the crash-induction technique. Following precurarisation with 0.02 mg/kg vecuronium and 0.1 mg fentanyl (group A and B) or NaCl 0.9% and 0.1 mg fentanyl (group C) preoxygenation via face mask was maintained until the patients reported heavy eye-lids or weariness or the precurarization-time attained 120 s. The patients then received 5 mg/kg thiopentone followed by 1.5 mg/kg succinylcholine (group B) or 0.08 mg/kg vecuronium (group A) resp. 0.1 mg/kg vecuronium (group C) directly before the thiopentone. Rapid intubation and scoring of the intubation condition was performed by an anaesthetist who was unaware of the grouping. The intubation time was defined as the interval from the end of the injection of the drugs until cuff inflation of the tracheal tube. All patients in group A and B could be intubated within 60 s, in contrast to only 15 patients in group C (p less than 0.05). The intubation conditions in the succinylcholine group and in the vecuronium group with divided doses showed no significant differences, while in group C the conditions were significantly worse. The modified crash-induction technique with vecuronium in divided doses could become beneficial in patients with contraindications of the use of succinylcholine who are at risk of aspiration. PMID- 2877595 TI - Age associated increase of C cell follicles in guinea pig thyroid glands. AB - The effect of aging on the formation of C cell follicles was examined in the thyroid gland of guinea pigs at various ages ranging from 1 to 29 months. The C cell follicles were demonstrated with the immunoperoxidase methods by using anticalcitonin and antisomatostatin antisera and with PAS reaction. They were already detected in 1-month-old guinea pigs but in low number. Thyroid glands from 1- to 14-month-old animals contained only a small number of C cell follicles and did not reveal the age-related increase. In aged guinea pigs (20- to 29-month old), a dramatic increase of C cell follicles was found, about 13 times as high as the number of other age groups. The C cell follicles through all age groups were present in large clusters of C cells. In the aged guinea pigs, nodular large aggregates of C cells regarded as C cell hyperplasia occurred and numerous C cell follicles were formed in the large cell aggregates. Thus, the conspicuous increase of C cell follicles in aged animals was associated with a proliferative abnormality of C cells. The C cells forming follicles showed moderate to weak immunoreactivity for calcitonin, whereas they showed very intense immunoreactivity for somatostatin. In addition, the colloidlike and flocculent materials stored in the follicular lumina, which were consistently PAS-positive, were weakly immunoreactive to somatostatin but nonreactive to calcitonin. PMID- 2877597 TI - On the use of priming with vecuronium for rapid sequence induction. PMID- 2877596 TI - Pharmacokinetics and pharmacodynamics of vecuronium and pancuronium in anesthetized children. AB - The pharmacokinetics and pharmacodynamics of vecuronium and pancuronium were determined in 12 children (3-6 yr) undergoing minor surgery under 60% nitrous oxide, 1 MAC halothane anesthesia. When the level of anesthesia and the electromyograph (EMG) recording of the adductor pollicis were stable, an intravenous bolus of vecuronium (100 micrograms/kg) or pancuronium (100 micrograms/kg) was administered. Plasma concentrations of the two muscle relaxants were determined for 6 hr after the administration by means of a fluorimetric assay followed by a thin layer chromatography. Plasma concentrations of vecuronium and pancuronium declined biexponentially in children and no metabolites could be detected in plasma. The elimination half-lives of vecuronium and pancuronium did not differ significantly. The volume of distribution at steady state (Vdss) was greater (P less than 0.05) after vecuronium (320 +/- 181 ml/kg; mean +/- SD) than after pancuronium (203 +/- 36 ml/kg). Plasma clearance of vecuronium (2.8 +/- 0.9 ml X min-1 X kg-1) was greater than that of pancuronium (1.7 +/- 0.2 ml X min-1 X kg-1; P less than 0.05). Plasma concentrations measured at 10%, 50%, or 90% recovery of the EMG response did not differ significantly for vecuronium and pancuronium. Thus the shorter duration of action of vecuronium is probably due to its greater apparent volume of distribution, as well as to its higher plasma clearance. Thus although the elimination half-lives are comparable, the plasma disappearance of vecuronium is more rapid than that of pancuronium. PMID- 2877598 TI - Prejunctional effects of vecuronium in the cat. AB - This study explored the prejunctional actions of vecuronium using the in vivo cat soleus nerve-muscle preparation. Vecuronium doses of 1 to 5 micrograms/kg iv suppressed the repetitive firing of the motor nerve endings, and the obligatory potentiation of the twitch response following high-frequency conditioning at 400 Hz for 10 s without attenuating neuromuscular transmission at 0.4 Hz. It was also found that extremely low doses of vecuronium had excitatory effects at the cat soleus motor nerve endings: doses of 0.5 and 1 microgram/kg iv evoked a modest postdrug repetitive firing of the nerve endings and a concomitant potentiation of the muscle responses. These dose-related agonist and antagonist activities suggest that at the motor nerve endings, vecuronium is a weak partial agonist. The major action of vecuronium at the motor nerve endings, however, was suppressive, and this antagonist action contributed to the neuromuscular blocking action of this muscle relaxant. PMID- 2877599 TI - Evaluation of esmolol in controlling increases in heart rate and blood pressure during endotracheal intubation in patients undergoing carotid endarterectomy. PMID- 2877600 TI - [Prolonged epidural analgesia with opiates]. PMID- 2877601 TI - Potential of interaction between the H1-antagonist astemizole and other drugs. AB - Astemizole is a potent H1-antagonist devoid of sedative effects, which was found at single oral daily doses to be very effective in the treatment of allergic rhinitis, allergic conjunctivitis, and urticaria. Its interaction potential on other drugs was studied in various ways. Studies on salivary antipyrine clearance, the 6-beta-hydrocortisol excretion, the elimination rate of ethanol and the indocyanine-green clearance are presented. No changes were observed. Astemizole also was given in combination with diazepam or alcohol. Psychomotor performance failed to show any effects. In none of these studies was there any evidence of interaction of astemizole on other drugs. This review summarizes the data available thus far. PMID- 2877602 TI - Assessing mistletoe toxicity. AB - To assess the potential toxicity of mistletoe ingestion, data were collected on 14 cases of ingestion of one to three berries or one or two leaves of American mistletoe (Phoradendron sp) from 1982 to 1985. Eleven patients ingested berries and three ingested leaves; none became symptomatic. Nine patients were observed at home without intervention except poison center telephone follow-up. Five had induced emesis, including two who were referred to emergency departments for evaluation, where no findings other than ipecac-induced vomiting were noted. Also reviewed were data on a total of 318 cases of mistletoe ingestion reported to the Food and Drug Administration Poison Control case reporting system between 1978 and 1983 (n = 177) and the American Association of Poison Control Centers national data collection system (n = 141) in 1984. The majority remained asymptomatic and no deaths were recorded. These data allow the conclusion that ingestion of one to three mistletoe berries or one or two leaves is unlikely to produce serious toxicity. PMID- 2877603 TI - Antagonism of xylazine-induced depression of shuttle-avoidance responses in dogs by administration of 4-aminopyridine, doxapram, or yohimbine. AB - The effectiveness of 4-aminopyridine, doxapram, or yohimbine as antagonists against xylazine-induced CNS depression in dogs was evaluated and compared, using the 2-way shuttle-avoidance paradigm. All drugs were given IV to 5 male dogs trained to avoid mild shock by jumping over a hurdle within 10 s after initiation of an audible tone. At dosages of 1 and 2 mg/kg of body weight, xylazine abolished or significantly decreased the mean number of avoidance responses and significantly increased the mean latency of avoidance responses. The analeptic 4 aminopyridine (0.5 mg/kg) did not significantly antagonize xylazine in all dogs. One dog convulsed both times it was given xylazine followed by 4-aminopyridine, but did not convulse when given either drug alone. Doxapram (5.5 mg/kg), a short acting analeptic and respiratory stimulant, was only partially effective in antagonizing xylazine, and its antagonistic actions were brief. Yohimbine (0.1 mg/kg), an alpha 2-adrenoreceptor-blocking agent, was superior to 4-aminopyridine and doxapram in its ability to antagonize xylazine-induced CNS depression. Yohimbine consistently increased the mean number of avoidance responses to the maximum of 8 and consistently decreased the mean latency of avoidance responses to control values in dogs given 1 or 2 mg of xylazine/kg. In dogs given 2 mg of xylazine/kg, yohimbine was significantly more effective than 4-aminopyridine or doxapram in its ability to increase the mean number of avoidance responses and decrease the mean latency of avoidance responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877604 TI - Pathogenicity and immunogenicity of piliated and nonpiliated phases of Moraxella bovis in calves. AB - Pathogenicity evaluations of Moraxella bovis strain EPP 63 grown in the piliated and nonpiliated phase indicated that the organism grown in the piliated phase induced clinical keratoconjunctivitis, whereas the organism grown in the nonpiliated phase did not induce disease under identical challenge conditions. Calves inoculated with culture grown in the piliated phase developed significantly (P less than 0.01) higher lesion scores than did calves inoculated with culture grown in the nonpiliated phase. Vaccination/challenge exposure evaluations indicated that calves immunized with vaccine prepared from piliated culture had significantly lower lesion scores than did control calves (P less than 0.001) or calves immunized with vaccine prepared from nonpiliated culture (P less than 0.05). Similarly, calves immunized with piliated vaccine developed a significantly higher antibody titer against purified pili. Nonvaccinated controls and calves immunized with nonpiliated vaccine did not develop a significant increase in antibody titer. The results indicate that M bovis pili constitute an important factor in the pathogenicity of keratoconjunctivitis and may be used as a vaccine in the control of keratoconjunctivitis in cattle. PMID- 2877606 TI - Controversies in the management of Zollinger-Ellison syndrome. PMID- 2877605 TI - Treatment of resistant acromegaly with a long-acting somatostatin analogue (SMS 201-995). AB - Six patients with resistant acromegaly were given a long-acting somatostatin analogue (SMS 201-995) for 5 to 12 months. The clinical response was dramatic; relief of headache occurred within minutes of the injection. The mean 24-hour growth hormone levels fell acutely after the administration of 50 or 100 micrograms every 12 hours, especially in four patients with small tumors (p less than 0.001). Dosages of up to 1500 micrograms/d were necessary to produce maximum lowering of growth hormone secretion in some patients. On long-term treatment, plasma somatomedin-C levels fell in all patients and became normal in four. Plasma immunoreactive levels of SMS 201-995 related inversely to growth hormone concentration: A reproducible threshold for growth hormone inhibition in five of the patients, ranging from 70 to 1200 pg/mL, was maintained for 6 to 8 hours after the injections. This somatostatin analogue is effective in the treatment of acromegaly, has no major side effects, and causes only transient changes in carbohydrate metabolism. PMID- 2877607 TI - [Periarteritis nodosa and Churg-Strauss granulomatous angiitis: the same entity?]. PMID- 2877608 TI - [Quality control of galenic preparations of nux vomica: proposal for a new method of extracting and assaying strychnine and brucine]. PMID- 2877609 TI - Prevalence of various enteropathogens in the feces of diarrheic and healthy calves. AB - The presence of various enteropathogens was examined in the feces of homebred dairy calves reared in a restricted geographical area of France (North West of County of Indre-et-Loire) during winter 1983-1984. Two distinct surveys were carried on: a case-control study including 32 diarrheic calves and 21 healthy calves bred in 53 different farms; and a separate study on nine diarrheic calves in another farm. The following infectious agents were looked for, by specific methods of detection: Escherichia coli K99 and E. coli lethal for mice, Salmonella species, Yersinia enterocolitica, Campylobacter jejuni, enterotoxigenic Clostridium perfringens, Chlamydia psittaci, rotaviruses, coronaviruses, Cryptosporidium. In the case-control survey, no enterotoxigenic E. coli (K99+) was detected in either group of calves. Four agents were more often detected in diarrheic calves than in healthy calves, i.e. rotavirus (12/32 vs 1/21), lethal E. coli (6/32 vs 1/21), Cryptosporidium (2/32 vs 0/21) and Salmonella typhimurium (1/32 vs 0/21). One at least of these four agents was present in 16 diarrheic calves (50%) vs only 2 healthy calves (10%) (P less than 0.01). On the other hand, the occurrence of Campylobacter jejuni and of C. perfringens, enterotoxin was similar in both groups of calves, accounting respectively for about 20% and 10% of total calves. Moreover, coronavirus-like particles were significatively associated with healthy calves (7/32 vs 11/21; P less than 0.05). In the other study, all the main categories of enteropathogens were detected throughout the period of observation in the same farm with the exception of enterotoxigenic E. coli. But each calf taken individually was rarely shedding more than two agents at a time. In addition, specific antibodies against C. perfringens enterotoxin, as tested in an ELISA test, were present in the serum of all the calves examined in both surveys. This study confirms the primary role of rotavirus and Cryptosporidium as agents of diarrhea in calves under three weeks. It also suggests the possible participation of E. coli strains that are lethal for mice and underlines the potential hazard for human health of bovine reservoirs of Campylobacter jejuni and enterotoxigenic C. perfringens. PMID- 2877611 TI - [Renin secretion. Mechanism and effectors]. AB - Renin secretion from juxtaglomerular cells of the kidney is controlled by several effector systems, such as renal perfusion pressure, renal nerve activity, salt load to the distal tubule and various humoral agents. The reactive behaviour of juxtaglomerular cells to these mechanisms is homologous to that of vascular smooth muscle cells of the kidney, i.e. manoeuvres inducing vasoconstriction inhibit renin secretion, whereas those inducing vasorelaxation stimulate renin secretion. This homology is partly explained by the fact that juxtaglomerular cells are modified smooth muscle cells. Intracellularly, an increase of cytosolic calcium has been identified as an inhibitory signal, whereas the major stimulatory signal appears to be cAMP (and the decrease of calcium). How intracellular calcium and cAMP are linked to the process of renin secretion, remains obscure. PMID- 2877610 TI - [Treatment of dilated cardiomyopathies. Recent findings]. AB - The drug therapy of decompensated cardiac insufficiency in dilated cardiomyopathies is based, still today, on the association of digitalis and diuretics, even though doubts had been expressed about the long term efficacy of glycosides. In the search for an ideal inotropic agent, several molecules recently synthesized are being investigated. The results obtained are not entirely satisfactory, either because the functional advantage is finally exhausted, or because of the frequency of side effects. Among the vasodilators, inhibitors of the conversion enzyme give better results by producing a substantial and lasting improvement of the ventricle performance, without tachyphylaxis or sympathetic compensation phenomenon. In some patients,the use of Beta-blockers could be beneficial, but the definitive proof is not yet furnished and the results are inconsistent. PMID- 2877612 TI - Factors contributing to the pathogenic behavior of Entamoeba histolytica. PMID- 2877613 TI - The natural history of Japanese encephalitis virus. PMID- 2877614 TI - Virulence factors of Bordetella pertussis. PMID- 2877615 TI - Substrate utilization by Campylobacter jejuni and Campylobacter coli. AB - An attempt was made to elucidate in Campylobacter spp. some of the physiologic characteristics that are reflected in the kinetics of CO2 formation from four 14C labeled substrates. Campylobacter jejuni and C. coli were grown in a biphasic medium, and highly motile spiral cells were harvested at 12 h. Of the media evaluated for use in the metabolic tests, minimal essential medium without glutamine, diluted with an equal volume of potassium sodium phosphate buffer (pH 7.2), provided the greatest stability and least competition with the substrates to be tested. The cells were incubated with 0.02 M glutamate, glutamine, alpha ketoglutarate, or formate, or with concentrations of these substrates ranging from 0.0032 to 0.125 M. All four substrates were metabolized very rapidly by both species. A feature of many of these reactions, particularly obvious with alpha ketoglutarate, was an immediate burst of CO2 production followed by CO2 evolution at a more moderate rate. These diphasic kinetics of substrate utilization were not seen in comparable experiments with Escherichia coli grown and tested under identical conditions. With C. jejuni, CO2 production from formate proceeded rapidly for the entire period of incubation. The rate of metabolism of glutamate, glutamine, and alpha-ketoglutarate by both species was greatly enhanced by increased substrate concentration. The approach to the study of the metabolism of campylobacters here described may be useful in detecting subtle changes in the physiology of cells as they are maintained past their logarithmic growth phase. PMID- 2877617 TI - Evaluation of the diagnostic application of an enzyme immunoassay for Clostridium perfringens type A enterotoxin. AB - The diagnostic application of an enzyme immunoassay for Clostridium perfringens type A enterotoxin was evaluated. Test results from 100 individuals associated with C. perfringens gastroenteritis outbreaks and 111 control individuals were included. The assay sensitivity was 93.7%, and the assay specificity was 98.7%. PMID- 2877618 TI - [Morphology of malignant lymphoma]. PMID- 2877616 TI - Utilization of ornithine and arginine as specific precursors of clavulanic acid. AB - Ornithine and arginine (5 to 20 mM), but not glutamic acid or proline, exerted a concentration-dependent stimulatory effect on the biosynthesis of clavulanic acid in both resting-cell cultures and long-term fermentations of Streptomyces clavuligerus. Ornithine strongly inhibited cephamycin biosynthesis in the same strain. [1-14C]-, [5-14C]-, or [U-14 C] ornithine was efficiently incorporated into clavulanic acid, whereas the incorporation of uniformly labeled glutamic acid was very poor. [U-14C] citrulline were not incorporated at all. Mutant nca 1, a strain that is blocked in clavulanic acid biosynthesis, did not incorporate arginine into clavulanic acid. S. clavuligerus showed arginase activity, converting arginine into ornithine, but not amidinotransferase activity. Both arginase activity and clavulanic acid formation were enhanced simultaneously by supplementing the production medium with 10 mM arginine. PMID- 2877619 TI - [Radiologic diagnosis and radiation therapy of malignant lymphoma]. PMID- 2877620 TI - [Computed tomographic diagnosis of malignant lymphoma of the abdomen]. PMID- 2877621 TI - [Dynamic computed tomography in the diagnosis of lymphoma of the liver and spleen]. PMID- 2877622 TI - [Magnetic resonance tomography of the neck region]. PMID- 2877623 TI - [Magnetic resonance tomographic diagnosis of mediastinal lymphoma]. PMID- 2877624 TI - [Magnetic resonance tomographic diagnosis of abdominal manifestations of malignant lymphoma]. PMID- 2877625 TI - [Neuroradiologic diagnosis of malignant lymphoma]. PMID- 2877626 TI - [Radiotherapy of lymphogranulomatosis]. PMID- 2877628 TI - [Field control films for ultra-hard x-rays]. PMID- 2877627 TI - [Dosimetry in mantle-field radiotherapy of lymphogranulomatosis using ultra-hard x-rays]. PMID- 2877629 TI - [Clinical picture of malignant lymphoma]. PMID- 2877630 TI - [Radiotherapeutic indications in non-Hodgkin's lymphoma (nodal form)]. PMID- 2877631 TI - [Radiotherapy of extranodal manifestations of malignant lymphoma]. PMID- 2877632 TI - [Electron partial- amd total-skin irradiation (Tubinger method)]. PMID- 2877633 TI - [Radiotherapy of intracranial and spinal manifestations of malignant lymphoma]. PMID- 2877634 TI - [Conventional x-ray diagnosis of malignant lymphoma including angiography and lymphography]. PMID- 2877636 TI - [Sonographic diagnosis of nodal and extranodal manifestations of malignant lymphoma]. PMID- 2877635 TI - [Special radiology of osseous manifestations of malignant lymphoma]. PMID- 2877637 TI - [Computed tomography of the neck region]. PMID- 2877638 TI - [Computed tomographic diagnosis of malignant lymphoma of the thorax]. PMID- 2877640 TI - [Latent systemic periarteritis nodosa of predominantly renal and cerebral expression. Apropos of an anatomical case]. PMID- 2877639 TI - The modes of action of long chain alkyl compounds on the respiratory chain-linked energy transducing system in submitochondrial particles. AB - The interactions of long chain (greater than C7), alkyl compounds with tightly coupled, beef heart submitochondrial particles (SMP) have been investigated with respect to their effects upon respiratory chain-linked electron transfer and energy coupling capacity. Long chain alkyl alcohols, amines, free fatty acids, and methyl esters exhibit a general uncoupling effect, with stimulation of the succinate oxidase activity but inhibition of the NADH oxidase, in SMP. The degree of effectiveness is dependent on the nature of the functional group and the length of the alkyl chain. Submitochondrial particles depleted of F1 and the F1 inhibitor protein are similarly affected. Subsequent treatment with bovine serum albumin reverses the effects of free fatty acids and results in partial recovery of activity with alkyl amines, alcohols, and methyl esters. Differences between the effects of these alkyl compounds and those of sodium dodecyl sulfate, deoxycholate, palmitoyl carnitine, and palmitoyl CoA rule out detergent-like action as the explanation for these observations. These data suggest that specific lipophilic interactions with the membrane, modulated by the nature of the functional group, are responsible for the effects of these compounds on the energy transducing system of SMP. Analyses of the reduction kinetics of the cytochromes indicate that the sites of interaction of these compounds with the inner mitochondrial membrane are associated with the primary dehydrogenase of complex I and energy coupling site 2; alkyl amines possess an additional site of interaction in the region of complex III. PMID- 2877642 TI - [Food poisoning in a home for the aged]. PMID- 2877641 TI - Internal mammary artery grafts: technical factors influencing patency. AB - Eight hundred fourteen patients with internal mammary artery (IMA) coronary artery bypass grafts have been restudied 961 times with coronary arteriography, primarily to evaluate the patency of the grafts in the setting of symptomatic coronary occlusive disease. Their records were reviewed to assess graft patency as related to the technical aspects of coronary artery bypass surgery. Patency was evaluated using life-table analysis of the data. The method of harvesting the IMA played no role in patency. The left anterior descending coronary artery was the recipient coronary artery with the highest patency rate. The left IMA had a significantly higher patency rate than the right IMA. As a group, the IMAs had a significantly higher patency rate than saphenous vein grafts. However, there was no difference between right IMA grafts and saphenous vein grafts. The mammary artery grafts that remained patent throughout the study had a significantly higher blood flow after bypass than did those that became occluded (43.0 +/- 0.9 versus 28.9 +/- 1.8 ml/min; p less than .001). PMID- 2877643 TI - Effect of beta-blockade on right ventricular performance in patients with and without right ventricular dysfunction due to coronary artery disease. AB - To assess the effects of beta-blockade on right ventricular performance in patients with and without right ventricular dysfunction due to coronary artery disease, we performed radionuclide ventriculography on eight patients with normal right ventricular ejection fraction (RVEF greater than or equal to 35%) and 14 patients with mild to moderate right ventricular dysfunction (RVEF less than 35%) at rest. All patients had chronic stable angina pectoris, and nine patients had prior myocardial infarction. Radionuclide ventriculography was performed on placebo and during clinical beta-blockade (heart rate, 50 to 60 beats per minute and less than or equal to 20% increase in heart rate over baseline during stage I treadmill exercise, Bruce protocol) with the oral, cardioselective beta-blocking agent, betaxolol. The resting RVEF (mean +/- 1 SD) was 33% +/- 7% on placebo and 34% +/- 7% during clinical beta-blockade. Mean exercise RVEF was 40% +/- 8% on placebo and 39% +/- 8% during clinical beta-blockade. These differences were not statistically significant. Resting left ventricular ejection fraction ranged from 22% to 60% (mean, 42% +/- 8%). On placebo, one of eight patients with a resting RVEF greater than or equal to 35% had a normal exercise RVEF response (greater than or equal to 5% increment) whereas nine of 14 patients with resting RVEF less than 35% had normal exercise response. The discordant relationship between baseline RVEF and exercise response on placebo became less marked during clinical beta-blockade. We conclude that beta-blockade does not produce significant deterioration of right ventricular systolic function or right ventricular reserve either in patients with normal or in those with mild to moderately impaired resting right ventricular systolic function. PMID- 2877644 TI - Relaxation therapy for hypertension. Comparison of effects with concomitant placebo, diuretic, and beta-blocker. AB - We compared the effects of relaxation therapy in hypertensive patients taking placebo, a beta-blocker (atenolol, 100 mg/d), or a diuretic (chlorthalidone, 50 mg/d), and we also compared the effects of relaxation therapy with the effects of the latter two drugs alone. Blood pressures were measured not only in the relaxation therapists' office and at a hypertension clinic, but also in the patient's environment by means of 24-hour ambulatory blood pressure recordings. The effect of relaxation therapy, while statistically significant, was modest. There was no generalization of effect to ambulatory blood pressure. Atenolol was significantly more effective than relaxation in reducing both systolic and diastolic pressure. Chlorthalidone was significantly more effective than relaxation in reducing systolic but not diastolic pressure in the hypertension clinic only. The long-term effects of relaxation were independent of concomitant drug use, but within the actual relaxation sessions blood pressure dropped further during chlorthalidone than during placebo or atenolol treatment. PMID- 2877645 TI - Observer error in systolic blood pressure measurement in the elderly. A case for automatic recorders? AB - Measurement of systolic blood pressure (BP) in the elderly can be inaccurate due to observer errors such as terminal digit preference and expectation bias. Efforts to reduce these errors include use of trained observers, random-zero sphygmomanometers, and automatic BP recorders. To evaluate the value of an infrasonic recorder, the infrasonde, we compared simultaneous systolic BP determinations obtained directly by intra-arterial measurements, and indirectly by a standard cuff-mercury sphygmomanometer using clinic nurses (casual and serial measurements), a trained physician assistant (PA), and the Infrasonde in 36 elderly hypertensive men. All the indirect measurements correlated positively with the direct measurement. A terminal digit preference for zero occurred more frequently in the casual and serial readings compared with the Infrasonde and PA cuff readings: 45% and 51% vs 21% and 22%, respectively. Our data suggest that the Infrasonde is a reliable, alternative device for systolic BP measurement that eliminates observer biases associated with standard cuff BP recordings. PMID- 2877646 TI - Enzyme activity in mice with transplantable leukemia. AB - Activity of cobalt activated acylase, gamma-glutamyltransferase, leucylaminopeptidase and alanylaminopeptidase in serum and liver of mice with transplantable leukemias (L1210, L1210/ara-C, L1210/CH3-G, AKSL-4, plasmacytoma ADJ-PC-5) were determined. Adenosinotriphosphatase, 5'-nucleotidase and alkaline phosphatase were histochemically localized in lymphatic nodes and spleen. Among the investigated enzymes the rise in serum activity of cobalt activated acylase and gamma-glutamyltransferase was demonstrated. A substantial increase of leucylaminopeptidase and alanylaminopeptidase was shown in the liver. A decrease in the histochemical reactions of all the studied enzymes was observed. PMID- 2877647 TI - Ecological and epidemiological data on Hantavirus in bank vole populations in Belgium. AB - Epidemiological and ecological data of a Hantavirus infected bank vole population were collected using live-trapping methods. A close association between the distribution of HV-infected bank voles and wet habitat types was found. Several seroconversions were observed during the life of individual bank voles. All seroconversions occurred within the wet habitat types and only after a certain age was reached. Survival of HV-infected bank voles did not differ from not infected animals. In the laboratory passive antibody transfer was observed from antibody-positive females to their offspring. PMID- 2877649 TI - Spinal myoclonus associated with HTLV III/LAV infection. AB - We describe spinal myoclonus in a 35-year-old homosexual man with concurrent human T-cell lymphotropic virus type III/lymphadenopathy--associated virus (HTLV III/LAV) infection of the central nervous system as indicated by intra-blood brain barrier synthesis of HTLV III/LAV-specific IgG. The spinal myoclonus was characterized by asymmetric, rhythmic contractions of the abdomen with a frequency ranging between 40 and 70 per minute. The myoclonus was self-limited, resolving over the course of two months. Human T-cell lymphotropic virus type III/lymphadenopathy--associated virus should be considered among the viral causes of spinal myoclonus. PMID- 2877648 TI - The major protein of SAF is absent from spleen and thus not an essential part of the scrapie agent. AB - Scrapie-associated fibrils (SAF) play a controversial role in the discussion about the nature of the scrapie agent. In purification experiments SAF can be detected in brains of infected animals but not in spleen samples with similar titers of infectivity. Thus, SAF are not a constituent of the scrapie virus. PMID- 2877650 TI - Cerebral cation shifts and amino acids in Huntington's disease. AB - The cations, calcium, magnesium, sodium, and potassium, putative amino acid transmitters, and total protein contents were assessed in the frontal cortex, putamen, and substantia nigra of Huntington's disease (HD) patients and age matched nonneurologic control subjects. In the HD frontal cortex and HD substantia nigra, only small increases in sodium levels and decreases in potassium levels were observed, but in the HD putamen there were major cation shifts, suggesting a twofold increase of the extracellular space. In all three brain areas that were investigated, potassium was positively correlated with gamma-aminobutyric acid and in the putamen sodium was negatively correlated with the amino acid. These correlations suggest loss of gamma-aminobutyric acidergic neurons or nerve terminals in these areas. The elevation of sodium in the HD basal ganglia may be visualized in vivo by nuclear magnetic resonance of sodium. PMID- 2877652 TI - The bimaxillary mouthguard: a preliminary report of use in contact sports. PMID- 2877651 TI - Lipid and lipoprotein abnormalities associated with coronary heart disease in patients with insulin-dependent diabetes mellitus. AB - We measured serum lipid and lipoprotein levels in 63 insulin-dependent diabetic (IDD) patients (32 men, 31 women) and in 63 nondiabetic control subjects (32 men, 31 women) without coronary heart disease (CHD) and in 19 IDD patients (11 men, 8 women) and in 18 nondiabetic subjects (8 men, 10 women) with CHD. All diabetic patients had postglucagon C-peptide levels of less than 0.60 mmol/liter and none had signs of renal failure. Male IDD patients with CHD had higher levels of total cholesterol, low density lipoprotein (LDL) cholesterol, total triglycerides, very low density lipoprotein (VLDL) triglycerides and lower level of high density lipoprotein (HDL) cholesterol than male IDD patients without CHD. In female IDD patients, similar lipid and lipoprotein abnormalities were observed between the groups of diabetics with and without CHD except for total cholesterol, which was the same in both groups. A comparison between IDD patients without CHD and nondiabetic control subjects without CHD showed no difference in lipid and lipoprotein levels in males; female IDD patients without CHD showed even higher levels of HDL and HDL2 cholesterol and lower levels of VLDL triglycerides than nondiabetic controls. Our results indicate that in IDD patients without nephropathy and CHD, the lipid and lipoprotein levels do not differ from nondiabetic controls, but in IDD patients with CHD the lipid and lipoprotein pattern is similar to that known to be characteristic for nondiabetic patients with CHD. PMID- 2877653 TI - Cardiovascular research in space: considerations for the design of the human research facility of the United States Space Station. AB - NASA has recently celebrated its 25th anniversary, and it has been over 15 years since a man first set foot upon the lunar surface. The space agency is now making plans for "permanent" human presence in space to consist of an orbiting station staffed by both career astronauts and visiting investigators. What have we learned from the experience of two and a half decades of manned space flight? How well will the human organism tolerate longer duration or repeated space flights? What physical or psychological traits will be beneficial or detrimental to future space travellers? What additional considerations or investigations should be planned on the United States Space Station? This brief review summarizes our knowledge of space physiology as it relates to the cardiovascular system. Only actual flight information is utilized; no attempt is made to include the wealth of ground based simulation data, nor are areas remote to the cardiac system discussed. Gaps in current understanding are highlighted in a manner of suggested plans for future space flight investigations. PMID- 2877654 TI - The Aerospace Medical Research Laboratory: a leader in the development of life support. AB - The progress in the development of life support for the crewman parallels the changing flight envelope of the airplane and spacecraft. A constant in this history is man. In spite of elaborate attempts to refine the selection of the crew, the basic lists of requirements has not changed. Only the urgency and the need for providing the entire list of requirements have been seen. Generally, progress in the flight envelope has demanded more reliable and often more complex provisions to support the crew. The debate as to how this should be done has often centered on the argument about having man wear or carry the life support elements versus integration of these provisions into the vehicle. This debate initiated the concept of risks/benefits, a debate that has now reached all aspects of man's endeavors, including his medical care. This paper will discuss the major milestones of providing life support, some of the key contributors (a role that General Armstrong played in a great way), and how this has provided the base for the next steps in aviation and space operations. PMID- 2877655 TI - [Defined formula diet in the treatment of active Crohn disease]. PMID- 2877656 TI - Management of unstable angina pectoris with maximal medical treatment (combination of intravenous nitrates, beta-blockers, calcium antagonists and heparin). PMID- 2877657 TI - Myocardial salvage by medical therapy in acute myocardial infarction. PMID- 2877658 TI - An improved method for adrenalectomy of suckling rats. The influence of thrombin treatment and deoxycorticosterone substitution on survival and on hepatic and renal enzyme activities. AB - Adrenalectomy of suckling rats is complicated by a high mortality rate, caused by the loss of blood (early mortality) and by the disturbed sodium-potassium balance (late mortality). Treatment of the abdominal cavity with a thrombin solution and a daily administration of deoxycorticosterone glucoside (DOC) decrease the total mortality remarkably. DOC treatment has no influence on renal beta-glucosidase and beta-galactosidase as well as on hepatic tyrosine aminotransferase activity, whereas hepatic serine dehydratase activity exhibits a time- and dosage-dependent response to this hormone. The DOC effect is very likely a consequence of the glucocorticoid-like action of the synthetic hormone, which competes with the endogenous glucocorticoids for the hepatic receptor molecules. PMID- 2877659 TI - Physical and functional association of the atrial natriuretic peptide receptor with particulate guanylate cyclase as demonstrated using detergent extracts of bovine lung membranes. AB - Coupling of the atrial natriuretic peptide (ANP) receptor to particulate guanylate cyclase has been demonstrated kinetically and chromatographically using bovine lung plasma membranes and their detergent extracts. Addition of ANP to the membrane suspension stimulated guanylate cyclase activity 2-5-fold indicating the presence of ANP-sensitive particulate guanylate cyclase. The enzyme retained the ability to respond to ANP even after solubilization with digitonin. Characterization of the solubilized enzyme by gel filtration and affinity chromatography revealed that the ANP receptor and particulate guanylate cyclase exist as a functionally but not covalently linked stable complex. PMID- 2877660 TI - Degradation of dynorphin-(1-13) and dynorphin-(1-17) by the neuroblastoma cell membrane. Evidence for the involvement of a cysteine protease. AB - The membrane of mouse neuroblastoma N-18 cells degraded dynorphin-(1-13), dynorphin-(1-17), and Leu-enkephalin. The degradation of the former two peptides was inhibited strongly by N-ethylmaleimide, moderately by diisopropylphosphorofluoridate and phosphoramidon, and slightly by bestatin. When Leu-enkephalin was the substrate, however, the effects of phosphoramidon and bestatin were marked and those of N-ethylmaleimide and diisopropylphosphorofluoridate were negligibly small. Captopril did not affect the degradation of the two dynorphins and Leu-enkephalin, but inhibited the further cleavage of N-terminal fragments generated from dynorphin-(1-13) by the N ethylmaleimide-sensitive protease. Thus, a cysteine protease and, probably, a serine protease are responsible to the initial fragmentation of the dynorphins. PMID- 2877661 TI - Molecular mechanics studies of dermorphin. AB - Molecular mechanical simulations have been carried out on dermorphin. Presence of D-Ala2 at the N-terminus and L-Pro6 residue at the C-terminus indicated the probability of beta-turns. From the stereochemical considerations, three types- II', III' and V' - for the beta-turn at the N-terminus of the peptide and two types-I and III- for the C-terminus side of the peptide are possible. In our molecular mechanics calculations, we considered six folded and one extended conformations for dermorphin to asses the relative stabilities. Three of the six folded conformations are lower in energy and have the following general feature similar in energy, three hydrogen bonds, semirigid beta-sheet segment and favorable Tyr1-Tyr5 interaction. The presence of beta-sheet structure might play a role in mu-receptor selective interaction of dermorphin. PMID- 2877662 TI - Solid phase synthesis of somatostatin-28 II. A new biologically active octacosapeptide from anglerfish pancreatic islets. AB - Somatostatin-28 II, an octacosapeptide recently isolated from anglerfish pancreatic islets, was synthetized by the solid phase method along with its somatostatin-14 II and somatostatin-28 II-(1-12) corresponding domains. Homogeneity of the synthetic peptides was demonstrated by analytical RP-HPLC, thin layer chromatography and electrophoresis. The peptides were further characterized by amino acids analysis, fast atomic bombarding mass spectrometry and/or 252Cf plasma desorption mass spectrometry. Synthetic somatostatin-28 II and somatostatin-14 II displace equally well the potent agonist (Tyr0,D-Trp8) somatostatin-14 from its specific binding sites on anterior pituitary cells membranes. Both peptides activate adenylate cyclase from dispersed rat anterior pituitary cells. PMID- 2877663 TI - c-K-ras codon 12 GGT-CGT point mutation. An infrequent event in human lung cancer. AB - Hu-c-ras represent a family of oncogenes which are capable of inducing malignant transformation in the NIH/3T3 mouse cell line. Associated with this transformation are specific point mutations observed in the 12th and 61st codon of c-K-ras and N-ras and c-Ha-ras, respectively. These base changes generate, in some instances, a new restriction enzyme cleavage site and a restriction fragment length polymorphism (RFLP). One such RFLP has recently been reported for the mutation GGT-CGT at codon 12 of c-K-ras. Our data suggest that this point mutation is rarely present in human lung cancer and therefore is not likely to play a major role in cancer development. PMID- 2877664 TI - Localization of a human gene homologous to the PrP gene on the p arm of chromosome 20 and detection of PrP-related antigens in normal human brain. AB - Infectious fractions prepared from scrapie-infected hamster brains contain a protein, PrP 27-30, which shares antigenic determinants with polypeptides found in similarly prepared fractions from patients with Creutzfeldt-Jakob disease. cDNA sequences encoding the hamster PrP 27-30 identified homologous sequences in the human genome as well as in normal human brain mRNA preparations. Antibodies raised against the mouse PrP's identified antigenically related peptides in both normal hamster and human brain as well as in scrapie-infected hamster brain and CJD-affected human brain. By using in situ hybridization we localized the homologous human genomic sequences on the short arm of chromosome 20. Our results indicate that the reportedly unique proteins detected in human CJD preparations derive from normal human gene products. PMID- 2877665 TI - mRNA for the three human alcohol dehydrogenase subunits: size heterogeneity and developmental changes. AB - Human alcohol dehydrogenase consists of three types of subunits (alpha, beta, and gamma) which are governed by three separate loci. mRNA components for the three subunits were examined by Northern blot hybridization, using a common cDNA probe and specific oligonucleotide probes. A marked size heterogeneity of beta mRNA, ranging from 1.6 kb to 5.2 kb (of which the 2.4-kb and 3.5-kb were major), was observed in the adult liver. The mRNA for the gamma subunit was homogeneous (about 1.6 kb), and that for the alpha subunit contained a major 1.6-kb and a minor 4.3-kb component. The amount of mRNA was much lower (approximately 10% of adult) and the mRNA was less heterogeneous in the infant liver; i.e., an alpha mRNA (1.6 kb) and two beta mRNAs (a major 1.6 kb and a minor 3.5 kb), and no detectable gamma mRNA. The short beta mRNA, with 1.6 kb, could not be hybridized with a non-coding cDNA fragment that originated from the 3'-end of the 2.6 kb beta cDNA. The observed multiple ADH mRNAs, with a common coding region and different 3'-untranslated regions, are generated by utilization of multiple polyadenylation signals. The selection of polyadenylation signals and the rate of transcription of the three ADH loci are developmentally regulated. The 4.3-kb long mRNA, which was hybridized with both a- and beta-specific probes, could be related to the previously cloned "fused beta-alpha" cDNA. PMID- 2877666 TI - Effects on mitochondrial metabolism of CCA, one inducer of neuroblastoma differentiation. AB - CCA, a potent neuroblastoma differentiation inducer, was shown by oxygraphic measurements to reduce significantly the O2 consumption of whole neuroblastoma cells as of mitochondria purified from neuroblastoma or mouse cortex. The effect of CCA on the respiration was compared to those of oligomycin. Our results suggest that the molecular target of CCA is the matrix F1 catalytic component of the F0F1 mitochondrial ATPase. PMID- 2877667 TI - Classification of beta-adrenergic subtypes in immature rabbit bone marrow erythroblasts. AB - The beta-adrenergic receptors of immature rabbit bone marrow erythroid cells (proerythroblasts and basophilic erythroblasts) were identified. [125I]iodocyanopindolol bound to membrane preparations derived from these erythroblasts in a rapid, reversible and saturable manner. Scatchard analysis of binding data revealed a single class of binding sites (Hill coefficient of 0.954) with an apparent equilibrium dissociation constant (Kd) of 8 pM, and a density of binding sites (Bmax) of 1.53 pM/10(6) cells, corresponding to 920 receptors per cell. The binding of [125I]iodocyanopindolol was inhibited stereospecifically by concentrations of (-)-propranolol 2 orders of magnitude lower than by the (+) isomer. Only L-isoprenaline and L-adrenaline activated the adenylate cyclase of immature rabbit erythroblasts, while L-noradrenaline, a beta 1-adrenergic agonist, was inactive. The order of potency of different agonists for displacement of bound [125I]iodocyanopindolol was: isoprenaline greater than adrenaline greater than noradrenaline with respective EC50 (concentration required for half maximal inhibition of binding) of 7.9 X 10(-7) M, 1.5 X 10(-5) M and 7.9 X 10(-5) M. This agonist potency series did not change with differentiation of rabbit bone marrow erythroblasts. The inhibition of specific [125I]iodocyanopindolol binding to immature cells by beta 1- and beta 2-selective drugs (noradrenaline, practolol, procaterol and butoxamine) resulted in linear Hofstee plots. The inhibition curves obtained with procaterol and butoxamine, with apparent Kd values of 3.1 X 10(-9) M and 4.9 X 10(-9) M, further evidence that the high-affinity binding sites correspond to a homogeneous beta 2-receptor subtype. PMID- 2877668 TI - The coupling of metabolic to secretory events in pancreatic islets: inhibition by 2-cyclohexene-1-one of the secretory response to cyclic AMP and cytochalasin B. AB - In rat pancreatic islets perifused in the presence of 2-cyclohexene-1-one (CHX; 1.0 mM), the secretory response to either D-glucose or 2-ketoisocaproate, but not that evoked by the association of L-leucine and L-glutamine, was severely decreased. This coincided with a decreased stimulation of [45Ca] efflux from prelabelled islets, whereas the inhibitory action of D-glucose or 2 ketoisocaproate upon both [86Rb] and [45Ca] efflux appeared little or not affected. In the presence of D-glucose, the islets exposed to CHX were virtually unresponsive to either forskolin, theophylline or cytochalasin B. A severe decrease in the secretory response to forskolin was also observed in CHX-treated islets exposed to L-leucine and L-glutamine. Except for a somewhat lower sensitivity to NaF, no major change in adenylate cyclase activity or cyclic AMP production was observed in CHX-treated islets. The activity of protein kinase A was decreased in such islets but its responsiveness to cyclic AMP appeared unaltered. Transglutaminase activity was severely decreased in homogenates derived from CHX-treated islets. These findings suggest that CHX, possibly by lowering the GSH content of islet cells, impairs the functional capacity of the effector system for insulin release, in addition to and independently of any effect that it may exert upon nutrient catabolism and cationic fluxes in the islet cells. PMID- 2877669 TI - gamma-Glutamyl transpeptidase: a novel biochemical marker in inflammation. AB - gamma-Glutamyl transpeptidase (gamma-GT) plays an important role in the turnover of glutathione and protein biosynthesis. Because in inflammation both catabolic and anabolic steps are activated together with migration of cells, an alteration in gamma-GT activity was postulated to occur at the site of inflammation with the development of the inflammatory process. We discovered that gamma-GT activity was increased markedly at sites of inflammation produced in several ways in rats. A significant increase in enzyme activity appeared soon after the induction of inflammation. In carrageenin-induced acute inflammation, the paw tissue attained a 3- to 4-fold increase in enzyme activity within 4 hr; in established adjuvant arthritis, a 20- to 24-fold increase over its basal activity occurred in the rat paw tissue. The specific enzyme activity was 20-22 nmoles/min/mg protein in the cellular sediment of carrageenin-induced pleural exudate. In cotton granulomatous tissue it was 5- to 6-fold higher compared to the enzyme activity of the skeletal muscles. The in vivo increase in gamma-GT activity was prevented from occurring in proportion to the anti-inflammatory potencies of the test drugs given orally. The prevention of enzyme activity was observed with indomethacin in carrageenin induced edematous paw tissue and with phenylbutazone in both adjuvant arthritis and carrageenin-induced pleural exudate. Prednisolone was observed to be the most potent drug against cotton granuloma. Nonsteroidal anti-inflammatory drugs (NSAIDs) were not found to affect enzyme activity in vitro when incubated with cellular infiltrate from a cotton pellet granuloma. Differences in certain physico-chemical characteristics, viz. stability at 50 degrees, pH dependency and effects of solvents, were not discernible in between the enzyme activities of the untreated and edematous paw tissues. The studies thus suggest that measurement of gamma-GT in inflammation may prove to be a valuable biochemical marker for the assessment of anti-inflammatory activity of drugs in vivo. PMID- 2877670 TI - Heterogeneous properties of alpha 2 adrenoceptors in particulate and soluble preparations of human platelet and rat and rabbit kidney. AB - Alpha 2 adrenoceptors of the human platelet and rat and rabbit renal cortex were compared in binding studies using the selective antagonist ligand [3H]rauwolscine. Significant differences in the pharmacological characteristics of the alpha 2 adrenoceptor were observed between the tissues with reference to both absolute drug affinities as well as rank order of drug potency. Two subsets of the alpha 2 adrenoceptor sites could be described: one exhibiting equal affinity for the alpha 2 selective diastereoisomers, yohimbine and rauwolscine, and low affinity for the alpha 1 antagonist prazosin (human platelet); the other displaying significantly higher affinity for rauwolscine than yohimbine but also relatively high affinity for prazosin (rat and rabbit kidney). Digitonin solubilised alpha 2 adrenoceptors from these tissues identified by [3H]rauwolscine generally displayed reduced drug affinities. This was most apparent for agonists (10-50-fold lower) indicating separation of the soluble receptors from the guanine nucleotide binding proteins. However, the solubilised alpha 2 adrenoceptors retained the overall pharmacological properties of their respective membrane receptors, including rank order of drug potency, reflecting similar inter-tissue differences. These results suggest that the pharmacological differences in alpha 2 adrenoceptors observed are not species specific and are not related to variation in receptor effector coupling mechanisms or problems of ligand access due to membrane constraints. This may reflect true intrinsic differences in the molecular structure of these receptors. PMID- 2877671 TI - Studies on the mechanism of action of tiazofurin (2-beta-D-ribofuranosylthiazole 4-carboxamide). VI. Biochemical and pharmacological studies on the degradation of thiazole-4-carboxamide adenine dinucleotide (TAD). AB - In order to exert its antitumor effects, the C-nucleoside tiazofurin (2-beta-D ribofuranosylthiazole-4-carboxamide) is converted to the dinucleotide TAD (thiazole-4-carboxamide adenine dinucleotide), an inhibitor of IMP dehydrogenase (IMPD). With few exceptions, sensitive tumors (such as the P388 leukemia) have been found to accumulate substantially more of this inhibitory dinucleotide than resistant strains (exemplified by the colon 38 carcinoma). Previous studies have attributed this difference to a depressed capacity to synthesize TAD on the part of tumors refractory to tiazofurin. In the present study, a second contributory factor has been identified, viz. an enhanced ability to degrade preformed TAD. This degradation has been traced to a soluble phosphodiesterase present at high levels in tumors naturally resistant to tiazofurin. Using standard techniques, this TAD-phosphodiesterase has been purified 200-fold from the colon 38 carcinoma. The activity so purified readily hydrolyzed TAD and ADP-ribose, but exhibited a comparatively weak activity toward NAD and thymidine-5'-monophosphate nitrophenyl ester. ADP-Ribose was also an excellent inhibitor of the hydrolysis of TAD. It is concluded, on the basis of these results, that TAD phosphodiesterase plays an important role in the expression of the oncolytic activity of tiazofurin. The suggestion is also made that ADP-ribose may be the natural substrate for this enzyme. PMID- 2877672 TI - Evidence for tyrosine at the ligand binding center of beta-adrenergic receptors. AB - Beta 1- and beta 2-adrenergic receptor radioligand antagonist binding activities in plasma membrane preparations from mammalian lung, as well as amphibian and avian red blood cells, have been shown to be inactivated by agents which specifically alkylate tyrosine. In membrane preparations, protection against inactivation was afforded by both agonists and antagonists. In soluble purified preparations, antagonists but not agonists protected against inactivation. These results suggest that tyrosine is located at or near the ligand binding site of both beta 1- and beta 2-adrenergic receptors. PMID- 2877673 TI - [Tetrahydroisoquinolines as components of H2-antagonists. 27. H2 antihistaminics]. AB - In studies on structure-activity relationships of histamine H2-receptor antagonists, lamtidine-analogue derivatives of N-(3-hydroxyphenyl)guanidine and 5 and 7-hydroxy-tetrahydroisoquinoline were prepared and tested for their H2 antagonistic activity on the isolated guinea-pig atrium and on the histamine stimulated acid secretion of the anaesthetized rat. A further aim of the investigations was to examine the influence of a lengthening of the side-chain as well as the substitution of the aminotriazole with other H2-antagonistic components, on the pharmacological data of the above-mentioned isoquinoline derivatives. All compounds made showed only little H2-antagonistic activity on the guinea-pig atrium. At the acid secretion a noticeable activity especially of the 7-hydroxy-tetrahydroisoquinoline isomers could be observed. PMID- 2877674 TI - Acute effects of bunazosin on aortic, vertebral, coronary and renal blood flows of anesthetized dogs. AB - Effects of 4-amino-2-(4-butyrylhexahydro-1H-1,4-diazepin-1-yl)-6,7-dime thoxy quinazoline (bunazosin, E-643, Detantol) on aortic, vertebral, coronary and renal blood flows were investigated in anesthetized open-chest dogs. Bunazosin 1, 10 and 100 micrograms/kg i.v. dose-dependently decreased aortic blood pressure (AoP) and inhibited the increase in AoP by phenylephrine 5 micrograms/kg i.v. However, the increase in AoP by norepinephrine 0.5 microgram/kg i.v. remained even after bunazosin 100 micrograms/kg i.v. and was almost undetectable after additional administration of yohimbine 1000 micrograms/kg i.v. A hypotension by bunazosin persisted more than 15 min, but dose-dependent increases in heart rate (HR) induced by bunazosin 1, 10 and 100 micrograms/kg i.v. restored within 2 min. Bunazosin 100 micrograms/kg i.v. significantly but transiently increased aortic blood flow and decreased renal blood flow. Vertebral and coronary blood flows were not significantly changed. Left ventricular dP/dt was transiently increased. Calculated total peripheral vascular resistance and coronary vascular resistance were transiently but significantly decreased. No significant changes were observed in both vertebral vascular resistance and renal vascular resistance. The results indicate that bunazosin maintains the blood flows to brain, heart and kidney, and is continuously lowering AoP without significant changes in HR. PMID- 2877675 TI - The effect of proteoglycans, collagen and lysyl oxidase on the metabolism of low density lipoprotein by macrophages. AB - To study the interactions of lipoproteins, connective tissue components and cells, mouse peritoneal macrophages were incubated in the presence of human low density lipoproteins (LDL) that had been complexed with pig aortic proteoglycans (PG) or incubated in the presence of soluble collagen and/or lysyl oxidase, which catalyses the formation of cross-linkages in collagen and elastin by oxidising epsilon-amino groups of lysine residues to aldehydes. Soluble and insoluble PG LDL complexes increased the incorporation of [3H]oleate into cellular cholesteryl esters (CE) 1.6- and 2.8-fold, respectively, while LDL incubated with collagen and lysyl oxidase had no effect compared to control LDL. As judged on the basis of incubations with fucoidin, spermine and 125I-labelled lipoproteins, the mechanism of internalisation of the PG-LDL complexes is different from that of acetylated LDL or dextran sulphate-LDL complexes. The formation of PG-LDL complexes in the arterial intima may lead to an increased uptake of lipoproteins by intimal macrophages during the early phase of atherogenesis. PMID- 2877676 TI - Restriction-fragment-length polymorphisms in the A-I-C-III gene complex occurring in a family with hypoalphalipoproteinemia. AB - Two restriction-fragment-length polymorphisms in the apolipoprotein A-I-C-III gene complex were defined by digestion with PstI and SacI in a family with hypoalphalipoproteinemia. These polymorphisms established a PstI + /SacI - haplotype which may constitute a linkage marker for this condition within the family. PMID- 2877677 TI - Differential interactions of "prosexual" drugs with 5-hydroxytryptamine1A and alpha 2-adrenergic receptors. AB - Radioligand binding studies were used to analyze the interactions of six "prosexual" drugs with 5-hydroxytryptamine1A (5-HT1A) and alpha 2-adrenergic receptors in rat brain membranes. Three drugs that facilitate seminal emissions and/or ejaculations [8-hydroxy-2-n-propylaminotetralin (8-OH-DPAT), 5-methoxy dimethyltryptamine, and RDS-127] are potent and selective inhibitors of [3H]8-OH DPAT binding to 5-HT1A receptors. By contrast, three drugs with primary sexual arousal effects (yohimbine, imiloxan, and idazoxan), are potent agents at alpha 2 adrenergic receptors labeled by [3H]yohimbine. These data suggest that radioligand binding analysis of prosexual agents may elucidate the pathophysiology of sexual behavior. PMID- 2877678 TI - Autacoids and some mediators in allergic and non allergic forms. AB - The aim of this review is that to examine some among the most important mediators involved in the onset of autacoid-mediated allergic and non-allergic symptomatology. Autacoids, such as histamine and arachidonic acid derivatives (leukotrienes and prostaglandins), mediators derived from cell membrane, such as PAF-acether and other cell-derived mediators, such as PF4, are described. Special importance is given to the respective pharmacological actions and to the mechanisms by which these actions are performed (receptors, antagonisms, synergism) from whose complexity systemic reactions might ensue. Furthermore, a part of this study is dedicated to the complex interactions among biochemical systems of the body such as Kinins, Coagulation, Fibrinolysis and Enzymatic Activity Mediators that can interfere with these interactions and support some pathologies. Besides, a chapter is devoted to Neurogenic Inflammation and therefore to Substance P and other neuropeptides. PMID- 2877679 TI - Influence of genetic predisposition to diabetes and obesity on mitochondrial function. AB - Inbred mice with the mutation diabetes C57BL/KsJ db+/db+ and the mutation obese C57BL/6J ob/ob displayed a total liver mitochondrial capacity to oxidize glutamate or succinate which was approximately eight times greater than the capacity of the C57BL/6J +/+ control mice. This increase in oxidation capacity was estimated by multiplying the observed twofold increase in each of the following components: total liver weight, the mitochondrial protein content per gram of liver, and glutamate or succinate respiration activity per milligram of liver mitochondrial protein. No significant difference in liver mitochondrial function and capacity for oxidation was observed between db+/db+ and ob/ob mutants, which indicated that these results may be primarily mediated by the genetic factors responsible for obesity and hyperphagia in these mutants, and not by the genetic traits associated with diabetes. These findings may provide a biochemical foundation in support of the thrifty gene hypothesis. PMID- 2877680 TI - Intravenous opiates and benzodiazepine sedation. PMID- 2877681 TI - Antagonism of profound neuromuscular blockade induced by vecuronium or atracurium. Comparison of neostigmine with edrophonium. AB - The effectiveness of neostigmine 0.07 mg kg-1 and edrophonium 0.8 mg kg-1 as antagonists of profound neuromuscular blockade induced by vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1 was studied in 59 healthy patients. The antagonists were administered 5 min after total ablation of the twitch response and the end point of recovery was a train-of-four ratio of 70%. In 30 patients given vecuronium the mean time to reach this point (duration TOF70) was 66.7 min in the control group (no antagonist), 43.5 min in the group given neostigmine and 59.8 min in the group given edrophonium. The duration TOF70 was shorter in the neostigmine group than in the control (P less than 0.01) and edrophonium (P less than 0.01) groups. The duration TOF70 did not differ from control in the edrophonium group. In 29 patients given atracurium, the durations TOF70 were 66.4, 44.1 and 54.9 min in the control, neostigmine and edrophonium groups, respectively. The durations TOF70 in the neostigmine (P less than 0.01) and edrophonium (P less than 0.01), groups were shorter than control. The duration TOF70 of the neostigmine group was shorter than in the edrophonium group (P less than 0.01). These results show that profound neuromuscular blockade cannot be rapidly antagonized by either of these two agents, but if reversal is required under these circumstances, neostigmine would be the more effective drug. PMID- 2877682 TI - Reappearance of the train-of-four after neuromuscular blockade induced with tubocurarine, vecuronium or atracurium. AB - The characteristics of train-of-four recovery after atracurium or vecuronium were studied, under enflurane anaesthesia, and compared with those associated with tubocurarine-induced blockade. Ten patients each received vecuronium 0.1 mg kg-1, atracurium 0.5 mg kg-1 or tubocurarine 0.5 mg kg-1. Neuromuscular blockade was calculated as the percent depression of the first twitch, and was determined at the time of reappearance of the second, third and fourth twitches of the train-of four. The pattern during recovery from blockade induced by the three neuromuscular blocking agents was similar, with T2, T3 and T4 reappearing at approximately 93%, 89% and 86% residual blockade, respectively. These results are different from those previously reported by Lee (1975) indicating that, under enflurane anaesthesia, the train-of-four count may give an incorrect estimate of the degree of neuromuscular blockade. PMID- 2877683 TI - Comparison of visual and measured train-of-four recovery after vecuronium-induced neuromuscular blockade using two anaesthetic techniques. AB - This study evaluated train-of-four recovery after the administration of vecuronium, comparing measured with visually observed responses. Responses to supramaximal stimuli of the ulnar nerves were measured by a force transducer, and compared with visually observed movements of the contralateral thumb. For the 10 patients anaesthetized with nitrous oxide and enflurane, the second, third and fourth twitches visually reappeared at 84 (+/- 10)%, 76 (+/- 11)%, and 70 (+/- 12)% measured blockade, respectively. For the other 10 patients, anaesthetized with a narcotic-barbiturate technique, the second, third and fourth twitches reappeared at 81 (+/- 8)%, 68 (+/- 9)%, and 59 (+/- 11)%. These results were not different for the two anaesthetic techniques. PMID- 2877684 TI - Effects of transplantation and resection of a radiation-induced rat insulinoma on glucose homeostasis and the endocrine pancreas. AB - Twenty-one days after s.c. subscapular transplantation of a radiation-induced insulinoma, male NEDH rats exhibited hyperinsulinaemia and hypoglycaemia. These features were associated with islet atrophy, degenerative changes in pancreatic A and B cells, and decreases in the pancreatic contents of insulin, glucagon and somatostatin. The immunoreactive glucagon and somatostatin contents of extrapancreatic tissues of insulinoma-bearing rats were unchanged. Surgical resection of the tumour resulted in an immediate fall of plasma insulin, attaining concentrations similar to those of anaesthetised control rats by 10 min. The estimated half-life of insulin was 3.5 min. Hypoglycaemia persisted until 60 min after resection, followed by hyperglycaemia of 1-2 days duration. Glucose tolerance was impaired 1 day after tumour resection despite the coexistence of raised insulin concentrations. Evidence for abnormal pancreatic B cell function was gained by injection of arginine which failed to evoke a plasma insulin response in the resected rats. Two days after resection, plasma glucose and insulin concentrations were similar to those of control rats. Plasma glucose and insulin responses to glucose and arginine were suggestive of tumour recurrence by 12 days. A single large encapsulated tumour was eventually observed in each rat, with resection giving a 17-56 day prolongation of life. PMID- 2877685 TI - Coated pit formation: a membrane function involved in the regulation of cellular iron uptake. AB - Diferric-transferrin induces a marked increase in the number of coated pits on the reticulocyte membrane. This increase is followed by a decline, often to below the initial number. Since a good correlation was found between the rate of iron uptake and the number of coated pits, but not between the rate of transferrin recycling and the coated pit count, it is likely that coated pit formation is necessary for the removal of iron from transferrin. The decline in the number of transferrin-induced coated pits was observed only when haem synthesis was undisturbed, indicating that the accumulation of intracellular haem inhibits coated pit formation. Based on these results we suggest that haem regulates the rate of iron uptake by inhibiting iron removal rather than receptor recycling. PMID- 2877687 TI - Electrophilic amination of a single methionine residue located at the active site of D-amino acid oxidase by O-(2,4-dinitrophenyl)hydroxylamine. AB - O-(2,4-Dinitrophenyl)hydroxylamine is a rapid active-site-directed inhibitor of D amino acid oxidase: modification results in specific incorporation of an amine group into an accessible nucleophilic residue with concomitant release of 2,4 dinitrophenol. The reaction is prevented by the competitive inhibitor benzoate, indicating an active-site-directed reaction. A stoichiometry of 1-1.5 mol of amine residues per enzyme bound flavin adenine dinucleotide monomer was observed at pH 7.0. Amino acid and sequence analyses show that His-217 is not the target of the modification reaction. Dependence of the modification on pH, model studies on functional groups present on amino acids, and thiolysis studies on aminated enzyme collectively indicate that the modification is located on a methionine residue at or near the active site of the enzyme. Aminated enzyme, although spectrally similar to native enzyme, exhibits a 7-9-nm blue shift in the 455-nm flavin absorption. Benzoate perturbs the spectrum of aminated enzyme, but binding relative to native enzyme is much weaker (Kd ca. 300 times greater at pH 8.0). PMID- 2877686 TI - Is vibration white finger a primary sympathetic nerve injury? AB - Changes in the sympathetic nerve system have been suggested as the pathophysiological mechanism underlying vibration white finger (VWF). The aim of the present study was to investigate if experimental support for such a mechanism could be found in VWF. Drugs with a known effect on sympathetic alpha receptors were administered into the finger skin by iontophoresis and their effects on blood flow in the same area evaluated using a laser Doppler technique. The effects of noradrenaline (stimulating alpha-1 and alpha-2 receptors), phenylephrine (an alpha-1 stimulator), and B-HT 933 (an alpha-2 stimulator) were studied in 12 patients with vibration white finger and 12 healthy controls. The reactions to noradrenaline and B-HT 933 were similar in both patients and controls, but the reaction of the patients to phenylephrine was significantly weaker than the controls. In additional experiments in six patients and six controls concentration effect curves to phenylephrine were derived. The curves for the patients were shifted to the right--that is, they reacted less strongly than the controls at all doses of the drug which induced an appreciable vasoconstriction. The results of this study are compatible with the hypothesis that the alpha-1 receptor mediated responses are weakened in VWF. The predominance of alpha-2 receptors in the digital arteries has, on the basis of animal experiments, been suggested as a possible mechanism for Raynaud's phenomenon. PMID- 2877688 TI - Thrombospondin is a substrate for blood coagulation factor XIIIa. AB - Thrombospondin (TSP) is released from alpha granules of activated platelets, binds to platelet surfaces, and copolymerizes with fibrin. In the present experiments, we investigated the action of factor XIIIa (plasma transglutaminase) on TSP. Factor XIIIa catalyzed incorporation of [14C]putrescine into soluble TSP and ligation of TSP to itself and to fibrin intermediates. Proteolytic digestion of [14C]putrescine-labeled TSP with trypsin or thrombin yielded a labeled disulfide-bonded core of 90 or 120-130 kilodalton (kDa) subunits, labeled fragments of less than 10 kDa, and an unlabeled 30-kDa heparin-binding fragment, indicating the presence of multiple factor XIIIa reactive glutaminyl residues located in several domains of the molecule. TSP became ligated in fibrin clots formed from amidinated fibrinogen, i.e., fibrin that could not contribute lysyl residues to factor IIIa catalyzed cross-links. The disulfide-bonded core of TSP formed upon thrombin digestion copolymerized with fibrin as efficiently as intact TSP. However, a lower proportion of the disulfide-bonded core became ligated. These results indicate that TSP, both in clots and in solution, contributes glutaminyl and lysyl residues to factor XIIIa catalyzed ligation. Cross-linking may be important in stabilizing interactions among TSP, fibrinogen, or fibrin and other molecules in hemostatic plugs. PMID- 2877689 TI - Enhanced Ca2+-induced calcium release by isolated sarcoplasmic reticulum vesicles from malignant hyperthermia susceptible pig muscle. AB - To further define the possible involvement of sarcoplasmic reticulum calcium accumulation and release in the skeletal muscle disorder malignant hyperthermia (MH), we have examined various properties of sarcoplasmic reticulum fractions isolated from normal and MH-susceptible pig muscle. A sarcoplasmic reticulum preparation enriched in vesicles derived from the terminal cisternae, was further fractionated on discontinuous sucrose density gradients (Meissner, G. (1984) J. Biol. Chem. 259, 2365-2374). The resultant MH-susceptible and normal sarcoplasmic reticulum fractions, designated F0-F4, did not differ in yield, cholesterol and phospholipid content, or nitrendipine binding capacity. Calcium accumulation (0.27 mumol Ca/mg per min at 22 degrees C), Ca2+-ATPase activity (0.98 mumol Pi/mg per min at 22 degrees C), and calsequestrin content were also similar for MH-susceptible and normal sarcoplasmic reticulum fraction F3. To examine sarcoplasmic reticulum calcium release, fraction F3 vesicles were passively loaded with 45Ca (approx. 40 nmol Ca/mg), and rapidly diluted into a medium of defined Ca2+ concentration. Upon dilution into 1 microM Ca2+, the extent of Ca2+ dependent calcium release measured after 5 s was significantly greater for MH susceptible than for normal sarcoplasmic reticulum, 65.9 +/- 2.8% vs. 47.7 +/- 3.9% of the loaded calcium, respectively. The C1/2 for Ca2+ stimulation of this calcium release (5 s value) from MH-susceptible sarcoplasmic reticulum also appeared to be shifted towards a higher Ca2+-sensitivity when compared to normal sarcoplasmic reticulum. Dantrolene had no effect on calcium release from fraction F3, however, halothane (0.1-0.5 mM) increased the extent of calcium release (5 s) similarly in both MH-susceptible and normal sarcoplasmic reticulum. Furthermore, Mg2+ was less effective at inhibiting, while ATP and caffeine were more effective in stimulating, this Ca2+-dependent release of calcium from MH-susceptible, when compared to normal sarcoplasmic reticulum. Our results demonstrate that while sarcoplasmic reticulum calcium-accumulation appears unaffected in MH, aspect(s) of the sarcoplasmic reticulum Ca2+-induced calcium release mechanism are altered. Although the role of the Ca2+-induced calcium release mechanism of sarcoplasmic reticulum in situ is not yet clear, our results suggest that an abnormality in the regulation of sarcoplasmic reticulum calcium release may play an important role in the MH syndrome. PMID- 2877690 TI - Evidence for stable homodimers and heterodimers of gamma-glutamyltranspeptidase subunits under protein-denaturing conditions. AB - gamma-Glutamyltranspeptidase is synthesized as a core glycosylated propeptide (Mr 75,000) which is subsequently cleaved to yield a stable heterodimeric structure (subunit Mr 50,000 and 30,000). The propeptide represents an insignificant mass of the transpeptidase but higher molecular weight bands designated H1 (Mr 85,000) and H2 (Mr 100,000) are readily observed by protein staining or immunoblot analysis of the enzyme or crude membranes after SDS-polyacrylamide gel electrophoresis. Although H1 and H2 represent the predominant antigenic forms of transpeptidase in tissues which exhibit relatively low specific enzyme activity, neither their structure nor their physiological function is known. In order to determine the relationship between H1 and H2, and the large (L) and small (S) subunits of the transpeptidase, individual bands (H1, H2, L and S) of the purified renal enzyme were cut from a Coomassie-stained SDS gel, eluted and re electrophoresed. Isolated S produced S and dimers of S (Mr 60,000), while isolated L produced L and dimers of L corresponding to H2. Equivalent mixtures of L and S also produced H1. Utilizing IgG affinity-purified against either L or S, immunoblot analysis confirmed that H2 is a dimer of L, and H1 is a heterodimer of L and S. However, monoclonal IgG which recognizes both transpeptidase propeptide and native heterodimer did not react with H1. Thus, it is clear that isolated L and S can form and maintain unique dimeric structures during SDS-polyacrylamide gel electrophoresis. With this information it should now be possible to ascertain the basis for the apparent predominance of H1 and H2 in non-renal tissues. PMID- 2877691 TI - [Brain-specific proteins S 100 and reception of neuromediators by membrane preparations from the rat brain]. AB - Study on specific binding of ligands of various nervous cell membrane neuromediator receptors revealed that brain-specific proteins S100 modulated in a dose-dependent fashion the level of specific binding. Proteins S100 (but not BSA or blood gamma-globulins) changed the Kd values of the ligand-receptor complexes and the number of binding sites. The effects of proteins S100 were specifically blocked by antibodies to S100. Proteins S100 influenced the functions of acetylcholine, serotonin, dopamine, noradrenaline and GABA receptors but not of opiate, imipramine, histamine and benzodiazepine receptors. PMID- 2877692 TI - Conformational properties of somatostatin. VI. In a methanol solution. PMID- 2877693 TI - [Seasonal changes in the behavioral effects of neuroleptics on white rats]. AB - Summarized results of the experiments (conducted in 1981-1984) demonstrate seasonal rhythms of some behavioural effects (catalepsy and depression of locomotor activity) of haloperidol (0.5 mg/kg) and levomepromazine (5 mg/kg) in white rats. In intact rats neuroleptics were more effective in depressing high than low motor activity. Catalepsy induced by single administration of neuroleptics was more pronounced in spring and autumn months. A certain negative correlation exists between seasonal variations of neuroleptic catalepsy and the speed of monoamine (dopamine and serotonin) metabolism in the brain of intact rats. PMID- 2877694 TI - Effect of nicorandil, N-(2-hydroxyethyl)nicotinamide nitrate, a new anti-anginal agent, on contractile responses to alpha-1- and alpha-2-adrenoceptor agonists in isolated rabbit aorta. AB - Effects of nicorandil on contractile responses to alpha 1- and alpha 2 adrenoceptor agonists were examined in isolated rabbit aorta. Nicorandil (10(-6) or 10(-5) M) inhibited contractile responses to clonidine (CL) and BHT-920 in a concentration-dependent manner, but had no effect on the response to methoxamine (MO). Nifedipine (10(-6) and 10(-5) M) had no significant effect on responses to CL and MO, but it had a noticeable inhibitory effect on the response to BHT-920. In tissues pretreated with phenoxybenzamine, nicorandil (10(-5) M) inhibited the residual response to MO, and nifedipine (10(-5) M) inhibited responses to MO and CL. The relationship between maximum contraction and percent receptor occupancy was found to be nonlinear for MO, but was near linear for CL and BHT-920. The inhibitory effect of prazosin (pA2 of about 9) on MO and CL was much greater than that of yohimbine (pA2 of about 6). Nicorandil had no apparent or slight inhibitory effect on responses to potassium and Ca2+, and this inhibitory effect was much less than that of nifedipine. These results indicate that the responses induced by MO, CL, and BHT-920 in the rabbit aorta are due to activation of alpha 1-adrenoceptors. It is also suggested that nicorandil minimally affects voltage dependent Ca2+ influx and that differential effects of nicorandil on the responses to alpha 1 and alpha 2 agonists may be the result of differences in the amount of receptor reserve that exist for MO, CL, and BHT-920 in this blood vessel. PMID- 2877695 TI - [Endocrine polyadenomatosis: current diagnostic approach]. PMID- 2877696 TI - Polyarteritis involving the lower limbs associated with periosteal new bone formation. PMID- 2877697 TI - 5-Methoxy-N,N-dimethyltryptamine-induced analgesia is blocked by alpha adrenoceptor antagonists in rats. AB - The effects of the alpha-adrenoceptor antagonists prazosin, phentolamine and yohimbine upon 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)-induced analgesia were tested in the hot-plate, tail-flick and shock-titration tests of nociception with rats. Intrathecally injected yohimbine and phentolamine blocked or attenuated the analgesia produced by systemic administration of 5-MeODMT in all three nociceptive tests. Intrathecally administered prazosin attenuated the analgesic effects of 5-MeODMT in the hot-plate and tail-flick tests, but not in the shock titration test. Intrathecal yohimbine showed a dose-related lowering of pain thresholds in saline and 5-MeODMT-treated animals. Phentolamine and prazosin produced normal dose-related curves in the hot-plate test and biphasic effects in the shock titration and tail-flick tests. These results demonstrate a functional interaction between alpha 2-adrenoceptors and 5-HT agonist-induced analgesia at a spinal level in rats. PMID- 2877698 TI - The effect of alpha 2-adrenoceptor agonists on the acid secretory responses of rat isolated gastric mucosa to electrical field stimulation. AB - The effects of clonidine, UK-14,304, noradrenaline, para-aminoclonidine and phenylephrine were examined on the acid secretory response of the rat isolated gastric mucosa preparation to electrical field stimulation. Clonidine, UK-14,304, noradrenaline and para-aminoclonidine but not phenylephrine (10 microM) reduced the response of the gastric mucosa stimulated at 2.5 Hz; gastric mucosae stimulated at higher frequencies were insensitive to the action of these alpha 2 adrenoceptor agonists. The inhibitory effect of the selective alpha 2 adrenoceptor agonist UK-14,304 was antagonized by idazoxan but not by prazosin. These findings indicate that clonidine and other alpha 2-adrenoceptor agents inhibit the acid secretory response of the rat gastric mucosa to electrical field stimulation by an action at alpha 2-adrenoceptors, which are probably located on cholinergic nerve terminals. PMID- 2877699 TI - Effects of alpha-adrenoceptor agonists and antagonists on ouabain-induced arrhythmias and cardiac arrest in guinea-pig. AB - Effects of alpha-adrenoceptor agonists and antagonists with different affinity for alpha 1- and alpha 2-receptors on ouabain-induced arrhythmias in guinea-pigs were studied. Early arrhythmias, ventricular fibrillation and cardiac arrest were induced in anaesthetized guinea-pigs by the slow intravenous infusion of ouabain. Phenylephrine and yohimbine potentiated the cardiotoxicity of ouabain significantly whereas prazosin and clonidine showed significant antiarrhythmic effects and delayed the cardiac arrest. It is concluded that selective alpha 1 receptor stimulation and alpha 2-receptor blockade increases the cardiotoxic effects of ouabain and selective alpha 2-receptor stimulation and alpha 1 receptor blockade inhibits ouabain-induced arrhythmias and cardiac arrest in guinea-pigs. PMID- 2877701 TI - Pharmacokinetics and therapeutic efficacy of haloperidol decanoate after loading dose administration. AB - For this open study, we selected 21 chronic psychotic female in-patients (16 of them schizophrenics) who were being maintained on oral neuroleptics. After a wash out period, they were treated by intramuscular depot injections of haloperidol decanoate, once a month for four months. The dose was calculated from the previous oral dosage, and the amount of the first injection was double that of the three following injections. Relatively stable plasma levels of haloperidol were achieved with the first injection, and corresponded to those observed with oral medication. A very significant correlation was found between plasma level and the dose administered, but not between plasma level and therapeutic effect. The clinical condition of about two-thirds of the patients remained unchanged or improved, compared with the period of oral treatment. During the first two months of treatment, there was more rigidity and tremor, but from the third month, the extrapyramidal symptoms were less pronounced than during the period of oral neuroleptics. PMID- 2877700 TI - The effects of noradrenaline, B-HT 920, methoxamine, angiotensin II and vasopressin on mean circulatory filling pressure in conscious rats. AB - The effects of vasoactive substances on mean circulatory filling pressure (MCFP), an index of total body venous tone, were determined in conscious rats. Cumulative doses of saline (0.9% w/v NaCl solution), methoxamine (alpha 1-adrenoceptor agonist), B-HT920 (alpha 2-adrenoceptor agonist) noradrenaline and vasopressin, and individual doses of angiotensin II (AII), were infused into the rats. Mean arterial pressure (MAP), MCFP and heart rate (HR) were determined before and during the plateau responses to infusions of the vasoactive substances. The infusions of all the agonists caused a dose-dependent increase in MAP and a decrease in HR. The infusion of saline affected neither MAP nor HR. The infusions of saline and methoxamine did not affect MCFP while the infusions of B-HT 920, noradrenaline and AII increased MCFP. MCFP was slightly increased during the infusion of high doses of vasopressin. It was concluded that receptors for the alpha 2-adrenoceptor agonist and AII are involved in the control of venous tone. Receptors for the alpha 1-adrenoceptor agonist and vasopressin are not important for the control of venous tone. PMID- 2877702 TI - Does propranolol have an antipsychotic effect? A placebo-controlled study in acute schizophrenia. AB - Thirty-six acute schizophrenics were randomly assigned to dextro (d)-propranolol or placebo in a double blind trial lasting four weeks. All patients had a fixed dose of haloperidol during the first week, which resulted in an initial improvement in both groups. Thereafter, a deterioration towards base-line was seen. Six patients on placebo, but none on propranolol were treatment failures at the end of three weeks (P less than 0.001). Comparison of change in scores from week 2 to 4 showed significantly greater deterioration in the placebo group; d propranolol thus had a better effect than placebo in sustaining the initial improvement with haloperidol. The overall magnitude of clinical change from pre treatment scores is small, the majority of the patients showing little or no overall improvement. It is concluded that d-propranolol has a detectable therapeutic effect, which by inference must have a novel pharmacological basis, but this is not as potent as standard neuroleptics. PMID- 2877704 TI - Gamma glutamyl transpeptidase and mean corpuscular volume: their usefulness in the assessment of in-patient alcoholics. AB - Gamma glutamyl transpeptidase and mean corpuscular volume are shown to be of little value in the assessment of patients admitted to psychiatric beds for problem drinking. PMID- 2877703 TI - Orofacial dyskinesia, cognitive function and medication. AB - The presence of tardive dyskinesia in a sample of 43 patients with schizophrenia and 37 psychopaths who had been hospitalised for many years and exposed to large amounts of medication was assessed while testing their cognitive function. Subjects who showed no evidence of abnormal movements performed significantly better on the test of delayed recall, but there were no differences in performance on any of the other tests of cognitive function used. Multiple regression analysis revealed that age and the total lifetime dose of neuroleptic medication received (in chlorpromazine equivalents) were the only variables to predict the Abnormal Involuntary Movement Scale score, although a large amount of variance in this variable was unaccounted for. The duration of treatment with neuroleptics did not predict AIMS score. PMID- 2877705 TI - Post-traumatic stress disorder following combat exposure: clinical features and psychopharmacological treatment. AB - Post-traumatic stress disorder may follow combat stress or civilian psychological traumata. In 25 retrospectively studied patients, symptoms were severe in terms of number of DSM-III items fulfilled, chronicity, and severity of psychosocial disability. Antidepressants had good or moderate results in 67% of cases treated, but major tranquilisers were much less effective; response to drug treatment was not clearly related to somatisation symptoms, significant depression, or panic attacks. Pharmacotherapy appeared to have had a positive impact on psychotherapy in 70% of cases. PMID- 2877706 TI - Radioreceptor assay of serum neuroleptic concentrations in psychiatric patients. PMID- 2877707 TI - Anticholinergic anti-Parkinson medication for neuroleptic-induced extrapyramidal side effects. PMID- 2877708 TI - A controlled assessment of propranolol in the treatment of neuroleptic-induced akathisia. AB - Twelve patients with neuroleptic-induced akathisia were treated in a randomised, double-blind, cross-over design with propranolol and matching placebo. Propranolol caused significant decrements in both subjective and objective ratings of akathisia, but not in anxiety scores. This confirms prior findings of the efficacy of propranolol in akathisia induced by neuroleptic treatment. PMID- 2877710 TI - Boys with late descending testes. PMID- 2877709 TI - Clostridium perfringens and rheumatoid arthritis. PMID- 2877711 TI - Effects of divalent metal ions on the uptake of glutamate and GABA from synaptosomal fractions. AB - The effects of divalent metal ions on high affinity uptake glutamate and GABA were examined, using crude and purified synaptosomal fractions prepared from brains of DBA/2CBI. The uptake velocities of both amino acids are severely reduced in the presence of Cu2+, Fe2+ and Zn2+ but remain unaffected by Co2+. PMID- 2877713 TI - Spinal action of dermorphin, an extremely potent opioid peptide from frog skin. AB - Studies on the characteristics of spinally administered dermorphin, a novel heptapeptide isolated from the skin of South American Phyllomedusa frogs, indicated that this agent is 3-5000X more active spinal morphine on the hot plate, tail flick and writhing tests. This agent displays naloxone reversibility and cross tolerance to spinal morphine, and possesses all of the characteristics of a mu opiate receptor agonist. PMID- 2877712 TI - Opioid, cholinergic and alpha-adrenergic influences on the modulation of nociception from the lateral reticular nucleus of the rat. AB - The lateral reticular nucleus (LRN) has been identified as an area in the caudal medulla involved in the centrifugal modulation of spinal nociceptive transmission and withdrawal reflexes. The data presented in this report further support a role for the LRN in the modulation of nociceptive responses. It was confirmed in the present study that focal electrical stimulation in the LRN inhibits the nociceptive tail-flick (TF) reflex at low intensities of stimulation in lightly pentobarbital-anesthetized rats. Aversive effects, however, were typically produced at similar and higher intensities of stimulation in the LRN in the same rats in the awake state. It was also determined that an inhibitory modulation of nociceptive responses organized both spinally and supraspinally could be activated independently by muscarinic cholinergic or opioid mechanisms in the LRN. Microinjection of morphine into the LRN in conscious rats produced an antinociception in both TF and hot plate (HP) tests which could be attenuated significantly by naloxone, but not atropine, previously microinjected into the same site in the LRN. Carbachol microinjected into the LRN also produced an antinociception which was attenuated significantly by atropine but not naloxone previously microinjected into the same site in the LRN. In contrast, the microinjection of clonidine or norepinephrine into the LRN either did not affect or shortened significantly response latencies in the TF and HP tests. These results further establish that the LRN contributes to the modulation of nociception. Opioid and cholinergic influences in the LRN appear to independently activate inhibition of responding to nociceptive stimuli organized either spinally or supraspinally, although descending inhibition was most clearly activated. An action at alpha 2 adrenoceptors in the LRN, conversely, produces an hyperalgesia as reflected by shortened latencies to respond in TF and HP tests. PMID- 2877714 TI - Endorphinergic mechanisms in cerebral blood flow autoregulation. AB - The influence of naturally occurring opioid peptides (Met-enkephalin (Met-Enk), dynorphin (DYN), beta-endorphin (beta-EP)) as well as morphine and the opiate antagonist naloxone and specific antisera on cerebral blood flow autoregulation was studied in anesthetized, artificially ventilated rats. Local hypothalamic blood flow (CBF, H2-gas clearance technique) and total cerebral blood volume (CBV, photoelectric method) were simultaneously recorded. Autoregulation was tested by determining CBF and CBV during consecutive stepwise lowering of the systemic mean arterial pressure to 80, 60 and 40 mm Hg, by hemorrhage. Resting CBF decreased following Met-Enk, DYN, beta-EP or morphine administration without simultaneous changes in CBV. Naloxone administration, on the contrary, increased CBV without affecting local CBF. Autoregulation of cerebral blood flow was maintained until 80 mm Hg, but not completely at 60 and 40 mm Hg arterial pressure in the control group. General opiate receptor blockade by 1 mg/kg s.c. naloxone abolished autoregulation at all levels, since CBF and CBV passively followed the arterial pressure changes. Intracerebroventricularly injected naloxone (1 microgram/kg) as well as a specific antiserum against beta-EP, but not against Met-Enk or DYN, resulted in the very same effect as peripherally injected naloxone. The present findings suggest that central, periventricular beta-endorphinergic mechanisms might play a major role in CBF autoregulation. PMID- 2877715 TI - Effects of periventricular lesions on the release of somatostatin during perifusion. AB - Hypothalamic periventricular (PV) nucleus lesions reduce median eminence (ME) SRIF content by approximately equal to 80% without affecting non-stress plasma growth hormone (GH) levels or the GH response to stress. Our aim was to study the effects of PV lesions on SRIF released during perifusion of preoptic-anterior hypothalamic (PO-AH) tissue. Female rats received anterior or posterior PV lesions; sham-lesioned and intact rats served as controls. Non-stress and stress plasma GH levels were similar in all groups at 2, 4 and 16 weeks after surgery. At 18 weeks after surgery, the perifused PO-AHs of the PV- and sham-lesioned rats released similar amounts of SRIF, and these were higher (P less than 0.001) than amounts released from PO-AHs of intact rats. The PO-AHs from all groups showed similar increases in SRIF release after 56 mM K+. Two rats were chosen randomly from each group to assess ME SRIF content; PV lesions caused almost 80% depletion of SRIF, sham lesions did not. These results confirm that most SRIF neurons in the PV nucleus and 80% of ME SRIF content are not essential for the control of GH levels under non-stress conditions or for the GH response to stress and indicate that PV or sham lesions in the rostral forebrain enhance in vitro SRIF release, perhaps from neurons outside the PV nucleus. PMID- 2877716 TI - Effects of kynurenic acid on evoked extracellular field potentials in the rat olfactory bulb in vivo. AB - The effects of excitatory amino acid antagonists on extracellular field potentials in the olfactory bulb produced by lateral olfactory tract stimulation were analyzed in vivo. The two compounds tested, D-2-amino-5-phosphonovalerate and kynurenic acid, were administered by brain dialysis. Only kynurenic acid was able to effectively suppress the monosynaptic excitation of the major class of interneurons, the granule cells. This pharmacological profile suggests the involvement of non-NMDA receptors. PMID- 2877717 TI - Glutamate in rat brain cortex synaptic vesicles: influence of the vesicle isolation procedure. AB - Rat brain cortex synaptic vesicles have been isolated by 3 different procedures. The one of Hata et al. (J. Neurochem., 27 (1976) 139) gave synaptic vesicles with a high glutamate content, but also, as judged by [3H]ouabain binding and electron microscopy, with considerable contamination by plasma membrane vesicles. This did not allow a precise estimation of the glutamate content of each synaptic vesicle. The second procedure used (Life Sci., 21 (1977) 1075), in which the tissue is homogenized with an all glass homogenizer, yielded vesicles of higher purity, but with no glutamate. A slightly modified Kadota and Kadota procedure (J. Cell Biol., 58 (1973) 135) gave synaptic vesicles of a very high purity that were filtered on a Sepharose 4B column, and there, the synaptic vesicle fraction of highest purity was estimated to contain 3640 glutamate molecules in each glutamatergic vesicle. This is equivalent to an intravesicular concentration of 0.21 M, that is, at least 10 times higher than the glutamate concentration in the rat brain cortex. PMID- 2877718 TI - Tyrosine hydroxylase and monoamine oxidase-A activity increases in differentiating human neuroblastoma after elimination of dividing cells. AB - SY5Y neuroblastoma cells were treated with retinoic acid to induce differentiation of neuroblast-like cells and with aphidicolin (an inhibitor of DNA polymerase) to eliminate the flat cells present in the long-term cultures and masking some of the biochemical developmental changes. Catecholaminergic enzyme (tyrosine hydroxylase and monoamine oxidase-A) activity was consistently increased with development and the increase was significantly greater after aphidicolin-induced elimination of dividing, non-neuronal cells. PMID- 2877719 TI - Interaction of serotonin with somatosensory cortical neuronal responses to afferent synaptic inputs and putative neurotransmitters. AB - The present study was conducted to investigate the action of serotonin (5-HT) on synaptic transmission within local circuits of the rat somatosensory cortex. Responses of single somatosensory cortical neurons to activation of excitatory and inhibitory synaptic pathways or iontophoretic application of putative neurotransmitters were examined before, during and after microiontophoresis of 5 HT. Monoamine-induced changes in neuronal responsiveness were quantitatively assessed by computer-based analysis of peri-event histograms. 5-HT typically exerted a differential inhibitory effect on neuronal firing, such that stimulus induced responses were reduced relative to spontaneous discharge. In 16 of 24 (67%) of the cells tested, 5-HT depressed synaptically evoked excitation more than background firing such that "signal to noise" ratio was decreased. In some cases evoked spiking was reduced from control levels at doses of 5-HT subthreshold for producing direct depression of baseline firing rate. Cortical neuron excitatory responses to iontophoretically applied acetylcholine (8 of 13 cells) and glutamate (10 of 15 cells) were also reduced during microiontophoresis of 5-HT. A similar reduction in inhibitory efficacy was observed in 62% of the cases (10 of 16 cells) where 5-HT was interacted with GABA-induced depressant responses. Local administration of 5-HT also resulted in an antagonism of stimulus bound inhibition of firing (9 of 11 cells). These results are contrasted with previously observed facilitory effects of norepinephrine (NE) on cortical neuronal responsiveness to afferent synaptic inputs and putative transmitter agents. It is suggested that endogenously released 5-HT and NE may exert complementary modulatory-type actions on neuronal responsiveness as a means of regulating the transfer of sensory information through local cerebrocortical circuits. PMID- 2877720 TI - [Role of hypothalamic histaminergic systems in the regulation of vigilance states in cats]. AB - We have studied the effects of local injections of histaminergic and antihistaminic drugs on the sleep-waking cycle in the cat. Microinjections of alpha-fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine decarboxylase, in the ventrolateral posterior hypothalamus, where histamine immunoreactive neurons have been recently identified, resulted in a significant decrease in wakefulness (W) and increase in deep slow wave sleep (SWS). On the other hand, microinjections of SKF-91488 (Homodimaprit), a specific inhibitor of histamine-N-methyltransferase, increased W and decreased SWS and paradoxical sleep (PS). Microinjections of histamine also produced an increase of W, while this effect was abolished by pretreatment with mepyramine, an H1-histamine receptor antagonist. PMID- 2877722 TI - [Clinical use of island flaps in orthopedics]. PMID- 2877721 TI - [Action of idazoxan on tachycardia following electric stimulation of the thoracic sympathetic chain in the rat]. AB - Selective stimulation of sympathetic nerves of the pithed rat (instead of stimulation of the whole sympathetic outflow) induced a frequency-dependent increase in heart rate. This electrical-induced tachycardia is decreased by clonidine and increased by idazoxan. The effect of idazoxan was not observed in experiments using continuous stimulation of the sympathetic outflow. It is then concluded that alpha 2 antagonists are able to increase the electrical-induced tachycardia in the pithed rat as they do in the dog or the cat. PMID- 2877723 TI - Recognition of an unsuspected phaeochromocytoma during elective coronary artery bypass surgery. AB - A patient with a longstanding history of mild hypertension undergoing elective coronary artery bypass grafting exhibited extreme and paroxysmal elevations of systemic blood pressure immediately after separation from cardiopulmonary bypass. Conventional antihypertensive therapy (nitroprusside, hydralazine, propranolol) was ineffective, whereas phentolamine infusion produced a decrease in systemic blood pressure. These observations led to the discovery of a predominantly norepinephrine-secreting phaeochromocytoma. This case is noteworthy in that cardiopulmonary bypass may have served as a stimulus for tumour secretion of catecholamine. Possible mechanisms for this effect are discussed. PMID- 2877724 TI - Nutritional status and endocrine response to hemorrhage. AB - Hyperglycemia-inducing hyperosmolality has recently been proven beneficial in the maintenance of blood volume and extracellular fluid volume during early hemorrhagic hypotension. Fed animals benefitted from better plasma refill compared with starved ones when subjected to equal blood loss. Using lightly sedated fed and 24-30 h starved rats, hormones with relevance to glucose homeostasis were studied during 90 min of hemorrhagic hypotension of 70 mmHg (1 mmHg = 133.32 Pa). Marked differences in the overall hormonal developments were found between the two groups. In fed rats, insulin and glucagon responses were initially attenuated, while somatostatin increased to an early peak level at 30 min, returning to basal at 90 min. In starved rats, somatostatin increased gradually during the 90 min. Adrenaline release was massive in both groups. Corticosterone showed no increase from basal levels in the fed group during hemorrhage, while starved rats increased their basal level fourfold already at 30 min. These data are presented as evidence that changing nutritional status alters hormonal response to hypovolemic stress. PMID- 2877726 TI - Sports medicine. PMID- 2877725 TI - Intravenous abuse of propylhexedrine (Benzedrex) and the risk of brainstem dysfunction in young adults. AB - In 1949, amphetamine sulfate was replaced by propylhexedrine in the nasal decongestant agent Benzedrex because of psychosis, sudden death, and widespread abuse. Propylhexedrine is not without risks, and reported cases of psychosis, myocardial infarction, pulmonary vascular disease and pulmonary hypertension, and sudden death are well documented in the medical literature. We are reporting 2 cases of definite brainstem dysfunction and 5 cases of transient diplopia secondary to IV abuse of Benzedrex. This widely abused drug is prepared by heating Benzedrex and hydrochloric acid, and the resulting crystals are dissolved in water for injection. This agent is called "stove-top speed". All 7 patients had transient diplopia, within seconds after injection. One patient had evidence of a right-internuclear ophthalmoplegia, and another had a depressed right gag reflex and paralysis of the right half of the tongue. The deficits in these two patients, persisted for many months. In young adults with history of drug abuse, the IV use of Benzedrex should be considered in the differential diagnosis of transient or permanent focal brainstem deficits. PMID- 2877727 TI - Running: examination, diagnosis, and treatment. AB - Remember that athletes are a special breed of person. They are usually determined and progressive in their thinking. Athletics is an essential part of their lives, and many cannot do without the activity. Do not deprive them of this opportunity. To simply say "Stop what you are doing and the pain will go away" is not sufficient. You must examine, prod, and badger the athlete for answers. Help the athlete overcome the injury and put him on the right road to recovery. This is an essential part of practice. Not only will the athlete be delighted, but it will give the practitioner immense satisfaction to see the athletes happy and running. PMID- 2877728 TI - Approaches to the management of soft tissue defects of the malleolar region. AB - When considering plastic procedures in the malleolar region, it is crucial to remember the special characteristics of this area. The blood supply, the skeletal structure, and the position of the limb all contribute to the uniqueness of this region. The approaches and procedures depend on the nature and size of the defect. By being knowledgeable of the anatomy and intrinsic characteristics of the malleolar region, and adhering to the principles of plastic and tissue handling, the best possible results of soft tissue reconstruction will be obtained. PMID- 2877729 TI - Enhancement of methotrexate nephrotoxicity after cisplatin therapy. AB - We measured urinary levels of total protein, N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase, and adenosine deaminase-binding protein in ten children with osteogenic sarcoma who were receiving combination chemotherapy that included 12 doses of methotrexate (12 g/m2). Analysis of the changes in these sensitive markers of renal tubular damage permitted detection of subclinical methotrexate-induced nephrotoxicity. In the absence of cisplatin, methotrexate therapy was associated with significant but transient increases in each of the four markers. Irreversible nephrotoxicity, indicated by persistent rises in NAG and alanine aminopeptidase as well as increased serum creatinine levels, was associated with doses of methotrexate that followed the administration of cisplatin (400 mg/m2). The biphasic pattern of total protein and NAG excretion observed in all patients suggests more than one mechanism of methotrexate-induced nephrotoxicity. Monitoring renal tubular damage in patients who are receiving methotrexate in combined-drug regimens would provide useful information for scheduling nephrotoxic drugs in clinical trials. PMID- 2877731 TI - Differential expression of cell surface antigens and glial fibrillary acidic protein in human astrocytoma subsets. AB - We have characterized five distinct cell surface antigens of human astrocytomas and correlated their expression with the expression of glial fibrillary acidic protein (GFAP) and four previously defined cell surface markers of astrocytomas. One of the newly studied antigens, A4, which was originally detected on rat central nervous system (but not peripheral nervous system) neurons, is expressed on GFAP+ human astrocytoma cells, but not on GFAP- astrocytomas or a wide range of other neuroectodermal, epithelial, and hematopoietic cells. Antigens F19 (Mr 140,000/90,000 glycoprotein) and F24 (Mr 90,000 glycoprotein) also show restricted distribution and are expressed on subsets of neuroectodermal and mesenchymal cells. Antigens G253 (Mr 95,000 glycoprotein) and S5 (Mr 120,000 glycoprotein) are more widely distributed on the cultured cell panel. The distribution of these antigens was determined on a series of 22 astrocytoma cell lines and in normal brain tissue and the results were compared with the distribution of 5 additional glial cell markers: GFAP and cell surface antigens A010 (Mr 110,000 glycoprotein); AJ8 (Mr 100,000 glycoprotein); LK26 (Mr 35,000 glycoprotein); and Thy-1. Distinct patterns of expression on cultured astrocytomas and in neural tissues were identified for all antigenic systems studied, and cell surface expression of antigen A4 was found to correlate closely with GFAP phenotype of cultured astrocytomas. The antigens described in this study provide new markers to study normal glial differentiation and to correlate the phenotypes and biological behavior of distinct subsets of astrocytomas. PMID- 2877730 TI - Implication of chromosome 11 in the suppression of neoplastic expression in human cell hybrids. AB - Cytogenetic analyses of intraspecies human HeLa X fibroblast hybrid cell populations have provided tentative evidence for the correlation of loss of a single copy of chromosomes 11 and 14 with reexpression of tumorigenicity. In this study paired combinations of nontumorigenic and tumorigenic segregant HeLa X fibroblast hybrid cells from two independent fusion events were examined for the presence or absence of normal chromosomes 11 and 14. In human hybrid cell lines the parental origin of chromosomes can be distinguished on the basis of restriction fragment length polymorphisms. Genes for c-Ha-ras, insulin, and apolipoprotein A-1 on chromosome 11 and a polymorphic locus AW101 on chromosome 14 were used as Southern hybridization probes. Analysis of DNA from the parental fibroblast and HeLa cell lines and their nontumorigenic and tumorigenic hybrids showed the loss of a fibroblast chromosome 11 in four of the tumorigenic segregants and a HeLa chromosome 11 in a fifth hybrid cell line. This latter segregant has, interestingly, also lost a copy of chromosome 14 of fibroblast origin. There was no obvious correlation of loss of a copy of normal chromosome 14 and reexpression of tumorigenicity in any of the other hybrid cell populations. Our conclusion from these observations is that gene(s) that map to normal chromosome 11 might be involved in control of tumorigenic expression in these human hybrid cells. PMID- 2877732 TI - Retroviruses of human T cells: their role in the aetiology of adult T-cell leukaemia/lymphoma and the acquired immune deficiency syndrome. PMID- 2877733 TI - The erbB gene and the EGF receptor. AB - The epidermal growth factor (EGF) receptor is a plasma membrane glycoprotein. It contains four distinct segments: an N-terminal EGF binding domain which is exposed at the cell surface; a short transmembrane segment; a cytoplasmic domain with protein-tyrosine kinase activity; and a C-terminal regulatory segment. Binding of EGF to the external domain of the receptor activates the protein tyrosine kinase activity of the receptor, and this elevated kinase activity is presumed to be involved in the activation of cell growth. The v-erbB transforming gene of avian erythroblastosis virus is derived, by retroviral transduction, from the gene (c-erbB) which encodes the avian EGF receptor. The transforming capacity of v-erbB appears to result from truncation of the receptor. In erythroid cells, truncation of the N-terminal ligand binding domain is sufficient for transformation, whereas in fibroblasts removal of an additional C-terminal segment is required for transformation. The EGF receptor is subject to complex regulatory controls, including ligand activation, downregulation by internalization, autophosphorylation and autoregulation and transmodulation involving phosphorylation by kinase C. This review is centered around the hypothesis that the transforming capacity of the truncated v-erbB gene product results from a loss in sensitivity to regulators and the consequent activation of protein kinase activity. PMID- 2877734 TI - The role of the x gene in HTLV associated malignancy. AB - Future studies on mechanisms of human T-cell leukaemia virus (HTLV) induced T cell malignancy will focus on the role of the chi gene. This unique gene is found only in HTLV and the related bovine leukaemia virus, and is thought to be the transforming gene of these viruses, though direct proof of that role is still lacking. Recent studies indicate that the protein encoded by this gene has transcriptional regulatory properties similar to those of transcriptional regulatory proteins of other DNA viruses. An understanding of the mechanism of action of the HTLV chi protein will provide further insights into the hypothesis that cellular transformation and, ultimately, leukaemogenesis by HTLV is a result of aberrant transcription in T cells induced by the chi protein. PMID- 2877736 TI - Laboratory diagnosis of myocardial ischemia. AB - The evaluation of myocardial metabolic changes in ischemic heart disease remains centered on the coronary sinus pacing and sampling techniques established over the last 25 years. Lactate remains the marker of choice for most institutions, though centers with more sophisticated laboratories will always be trying to improve on the sensitivity and specificity for ischemia, perhaps using ATP catabolites and nucleotides and measuring coronary sinus flow. The diagnostic value of lactate changes is limited and probably not superior to a well-conducted 12-lead treadmill exercise electrocardiogram test, but it does provide an objective marker for reliable further study and evaluation of interventions. It is almost certainly in the research context that metabolic studies have their place--evaluating drugs, surgery, or angioplasty and perhaps shedding light on obscure entities, such as chest pain with normal coronary arteries and cardiomyopathies. Attention to detail and simplicity of study are more likely to lead to valuable results rather than concentrating on the complexities. Each laboratory should establish the reproducibility of its results before commencing any procedures. PMID- 2877735 TI - Treatment of silent myocardial ischemia with transdermal nitroglycerin added to beta-blockers and alprazolam. AB - Investigations into the mechanisms and characteristics of ischemic heart disease have increasingly documented evidence of myocardial ischemia in the absence of symptoms. Recent work using objective criteria of ischemic episodes confirmed that angina pectoris or its equivalents need not accompany myocardial ischemia and noted that these episodes appear to be quite common. The impact on prognosis awaits further study, but preliminary data suggest an adverse prognosis for patients with recurrent spontaneous silent vasoconstrictive ischemia. Furthermore, treatment of silent ischemic episodes with nitrates may be associated with reduced ischemia. Preliminary trials show reduction of the number, duration, and magnitude of silent ischemic episodes by transdermal nitroglycerin given to patients receiving beta-blockers. Therapy of acute ischemic syndromes should be designed to eliminate ischemia completely, not merely ameliorate pain. PMID- 2877737 TI - Circadian rhythm of heart rate in the rabbit: prolongation of action potential duration by sustained beta adrenoceptor blockade is not due to associated bradycardia. AB - Six litters of six young rabbits were injected intraperitoneally, two per litter, with saline, alinidine, or nadolol once or twice daily for two weeks. In four litters successful radiotransmissions of electrocardiograms were recorded once hourly for four days before and during treatment. Alinidine and nadolol produced an overall mean bradycardia in comparison with saline treated animals, the effect of alinidine exceeding that of nadolol. At 48-70 hours after the end of treatment the hearts were used for in vitro electrophysiological study. Nadolol, but not alinidine, induced a prolongation of action potential duration compared with that of saline treated littermates in both atrial and ventricular muscle. An incidental observation was that heart rate in the rabbit followed a circadian rhythm, heart rates being slower in the morning and faster in late afternoon and evening. The circadian rhythm was attenuated but not abolished by alinidine and nadolol. These results suggest that if prolongation of action potential duration by sustained beta blockade in patients after myocardial infarction contributes to protection against sudden death (by a class III antiarrhythmic action) then alinidine would not be expected to provide a comparable prophylaxis. PMID- 2877738 TI - Are opioid peptides co-localized with vasopressin or oxytocin in the neural lobe of the rat? AB - The content of vasopressin, oxytocin, neurophysin, leucine-enkephalin, methionine enkephalin, dynorphin-(1-13), and alpha-neoendorphin in the rat neurohypophysis was measured after different periods of dehydration and after depolarisation of isolated neural lobes and of neurosecretory nerve endings. The rates at which the amount of neurohypophysial hormone and opioid peptides decreased, and the changes in the ratios between the amount of vasopressin or oxytocin and opioid peptide in the neurohypophysis after dehydration and in the incubation medium after depolarization in vitro cast some doubt on, and can be explained by mechanisms other than co-localisation of the different peptides. PMID- 2877739 TI - Somatostatin-containing D cells exhibit immunoreactivity for rat somatostatin cryptic peptide in six mammalian species. An electron-microscopical study. AB - Antisera raised against rat somatostatin cryptic peptide (RSCP; corresponding to amino acids 63-77 of rat pro-somatostatin), somatostatin-28-(1-12) and somatostatin-28-(17-28) were used to compare the morphological distribution of these pro-somatostatin-derived sequences within the gastroenteropancreatic system of six mammalian species, including man. Using the immunogold staining procedure, RSCP, SS28-(1-12) and SS28-(17-28) immunoreactivity was found to be present in all the D cells of the tissues investigated. Extra-islet RSCP and SS28-(1-12) immunoreactive cells were also identified in some species. RSCP, SS28-(1-12) and SS-28-(17-28) immunoreactivities were also present in a single case of human duodenal somatostatinoma. Immunostaining of serial ultrathin sections from all specimens in this study revealed that RSCP and both somatostatin immunoreactivities were co-localised in a majority of the reactive cells. Corroborative evidence was obtained by double immunogold staining which further showed that RSCP, SS28-(1-12) and SS28-(17-28) immunoreactivities were co localised to individual secretory granules in D type cells, both normal and tumour. RSCP and SS28-(17-28) immunoreactivities were invariably co-localised, whereas SS28-(1-12) immunoreactivity was restricted to a sub-population of secretory granules. Our findings suggest that RSCP immunoreactivity is conserved in a number of mammalian species and is stored in each secretory granule type. Consequently, detection of the RSCP sequence may serve as a useful marker for somatostatin-producing systems throughout the diffuse neuroendocrine system. PMID- 2877741 TI - A physical map of 4 million bp around the Duchenne muscular dystrophy gene on the human X-chromosome. AB - Employing pulsed field gradient electrophoresis, we constructed a 4.5 million bp (Mb) Sfil restriction map of the human X-chromosomal region p21, harboring genes for Duchenne (DMD) and Becker Muscular Dystrophy. In a DMD patient with additional chronic granulomatosis and retinitis pigmentosa, the proximal 3.5 Mb is deleted. Another DMD patient, with additional glycerol kinase deficiency and adrenal hypoplasia, lacks at least 3.3 Mb in the middle region, including marker C7 but not B24, placing C7 closer to DMD. Another DMD patient has a partial pERT 87 deletion of minimally 140 kb. Truncated Sfil fragments in a female X:21 translocation patient place the junction probe XJ1.1 115 kb from the distal end of the normal fragment. Probe pERT-84 maps to the same fragment, within 750 kb of XJ1.1. PMID- 2877740 TI - Immunocytochemical demonstration of growth hormone, prolactin and somatostatin like immunoreactivities in the brain of larval, young adult and upstream migrant adult sea lamprey, Petromyzon marinus. AB - Growth hormone, prolactin and somatostatin-like immunoreactivities were demonstrated in the brains of larval, young adult (parasitic) and upstream migrant adult sea lampreys, Petromyzon marinus, by means of immunoperoxidase techniques. Growth hormone (GH) and prolactin (PRL) were observed within separate perikarya in the nucleus praeopticus, within fibers in the commissura praeinfundibularis, and in nerve endings within the neurohypophysis of larval and adult-stage lampreys. Cell bodies demonstrating immunoreactive growth hormone were more numerous than those reactive for prolactin. Unlike in the upstream migrant adult lamprey, no GH or PRL was demonstrated in the adenohypophysis of larval or parasitic lamprey. Somatostatin (SRIF)-like immunoreactive neurons were demonstrated in the nucleus commissurae praeinfundibularis, anterior and posterior pars ventralis hypothalami, pars dorsalis thalami, and the tegmentum motorium rhombencephali of larval, parasitic and upstream migrant adult lampreys. Many of the SRIF containing neurons within the hypothalamus were cerebrospinal fluid (CSF)-contacting cells. SRIF fibers were found throughout most of the brain predominating within the nucleus praeopticus, pars ventralis hypothalami, and the nucleus interpeduncularis. No SRIF immunoreactivity was found within the neurophyophysis. The possible functions of these peptides within the brain of the lamprey are discussed. PMID- 2877742 TI - Identification and characterization of a parasegment specific regulatory element of the abdominal-B gene of Drosophila. AB - We have characterized mutations of the Abdominal-B gene of the bithorax complex of Drosophila. We conclude that the gene contains two distinct genetic elements: one has a morphogenetic role and acts in parasegments 10, 11, 12, and 13, while the other acts on parasegment 14 and has primarily or exclusively a regulatory function. Evidence indicates that the latter suppresses the activity of the morphogenetic element of Abd-B and of other genes responsible for the development of sclerotic plates. The regulatory element also suppresses those BX-C genes and other homeotics that, in the absence of Polycomb or extra sex combs function, can become active in parasegment 14. PMID- 2877743 TI - Molecular structure of human lymphocyte receptor for immunoglobulin E. AB - We have isolated and sequenced a cDNA clone encoding the human lymphocyte receptor for IgE (Fc epsilon R). The deduced protein sequence reveals that Fc epsilon R consists of 321 amino acids, without any signal sequence, and is oriented with its N-terminus on the cytoplasmic side and its C-terminus on the outside of the cell. This molecule shows striking sequence homology with chicken asialoglycoprotein receptor (hepatic lectin), suggesting a possible role for Fc epsilon R in endocytosis. Fc epsilon R mRNA is expressed in B cells, B cell lines, and macrophage cell lines. It is not expressed in T cells or T cell lines, with the exception of an HTLV-transformed T cell line. mRNAs expressed in a macrophage line and in the latter T cell line differ in size from mRNA expressed in B cells. Human BSF-1 (or IL-4) induces the expression of Fc epsilon R mRNA in B cells, but not in T cells. PMID- 2877744 TI - A glia-derived neurite promoting factor with protease inhibitory activity belongs to the protease nexins. AB - A glia-derived neurite promoting factor (GdNPF) has serine protease inhibitory activity and in addition regulates the migration of neuronal cells. cDNA cloning of GdNPF is necessary for studying the physiological relevance and the mode of action of this protein and similar cell-derived protease inhibitors. Xenopus oocytes injected with rat glioma cells mRNA release this inhibitor. A rat cDNA clone coding for the previously purified glia-derived neurite promoting factor (GdNPF) was isolated upon hybridization-selected translation, followed by immunoprecipitation. The correct identity of this cDNA is proven by the presence of a sequence coding for a tryptic fragment from pure GdNPF. Northern analysis indicates that GdNPF mRNA is found almost exclusively in brain tissue and could be developmentally regulated. The same cDNA clone has been used to isolate full length rat and human GdNPF cDNA. The deduced human GdNPF amino acid sequence indicates that the protein is a member of a family of cell-derived protease inhibitors named protease nexins. PMID- 2877746 TI - Structure of the segmentation gene paired and the Drosophila PRD gene set as part of a gene network. AB - The sequence of paired, a pair-rule gene required for segmentation in Drosophila, is presented. A search for genes with domains homologous to the paired gene was initiated and three homologues from a set of 12 were characterized with respect to temporal or spatial expression and sequence homologies. All four are transcribed in early development, one in the oocyte and during cleavage stages in the form of a gradient. In addition to the prd-specific his-pro repeat, some of the 12 genes contain M-repeats and two new types of homeo boxes not detectable by hybridization with the two known classes of homeo boxes. The observed linking of gene sets through combinations of homologies coding for protein domains is consistent with a general network concept of gene action. PMID- 2877745 TI - Isolation, structure, and expression of even-skipped: a second pair-rule gene of Drosophila containing a homeo box. AB - We report the isolation, sequence, and transcriptional behavior of the Drosophila even-skipped (eve) gene, a member of the pair-rule class of segmentation genes. We show that the eve gene contains a homeo box and hence is related structurally to the pair-rule gene fushi tarazu and to homeotic selector genes. However, the eve homeo box differs significantly from those previously described and encodes a putative DNA recognition helix that would probably recognize different sequences. The eve gene resembles other pair-rule genes in showing a transient seven stripe zebra pattern during the blastoderm stage, but seven additional stripes arise soon thereafter. Together, these 14 stripes are required for the activation of coincident stripes of engrailed transcripts, leading to the subdivision of the embryo into compartmental and segmental units. PMID- 2877747 TI - Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila. AB - Extending our search for homologous domains of the Drosophila paired gene, two closely linked genes at the gooseberry locus have been isolated. Both genes are expressed with a single segment periodicity but with different spatial and temporal expression patterns. While the transcripts of one gene appear earlier and are equally distributed between ectoderm and mesoderm, those of the second gene accumulate preferentially in neuroblasts. The similarity of these expression patterns to the 14-band pattern of the paired gene suggests a functional relationship. Such a functional link may be reflected in the two structurally homologous domains shared with the paired gene: a new type of homeo box extended by 18 amino acids at the 5' end, and a new domain, the paired box, consisting of a sequence of 128-135 amino acids. Thus, together with the PRD repeat, the paired gene contains at least three different domains, each defining a gene set thought to be important for development. PMID- 2877749 TI - Excitatory and inhibitory responses mediated by subtypes of alpha-adrenergic receptors of hamster submandibular ganglion cells. PMID- 2877748 TI - A bipotential neuroendocrine precursor whose choice of cell fate is determined by NGF and glucocorticoids. AB - Adrenal medullary endocrine (chromaffin) cells and sympathetic neurons both derive from the neural crest. We have found that the embryonic adrenal medulla and sympathetic ganglia are both initially populated by precursors expressing neural-specific genes. By birth, however, the medulla consists largely of chromaffin cells. In primary culture, the medullary precursors have three developmental fates: in NGF they continue to mature into neurons and survive, whereas in glucocorticoid they either extinguish their neuronal properties and exhibit an endocrine phenotype, or else continue to develop into neurons but then die. These data suggest that, in vivo, the adrenal medulla develops through both the glucocorticoid-induced differentiation of bipotential progenitors and the degeneration of committed neuronal precursors, which have migrated into the gland. PMID- 2877750 TI - Effects of ethinyl estradiol and tamoxifen on liver DNA turnover and new synthesis and appearance of gamma glutamyl transpeptidase-positive foci in female rats. AB - We investigated possible mechanisms associated with promotion of hepatocarcinogenesis by the synthetic estrogens mestranol (M) and ethinyl estradiol (EE). Our first objective was to determine whether chronic EE treatment was associated with hepatotoxicity accompanied by regenerative hyperplasia. Female Sprague-Dawley (SD) rats were partially hepatectomized and their liver DNA prelabeled with [3H]thymidine. Two weeks later the rats were treated with EE at three doses or M (using timed-release tablets implanted s.c.) or with 0.05% phenobarbital (PB) in the diet. The rats were killed 6 weeks later and the amount of [3H]thymidine remaining in liver DNA determined. The results showed that none of the promoters caused hepatotoxicity as detected by the loss of prelabeled DNA. EE but not M or PB caused a dramatic dose-dependent enlargement of the pituitary. Subsequent experiments were carried out to define the dose-time response of liver DNA synthesis to treatment with EE, M and PB. Female SD rats were treated with these agents and [3H]-thymidine incorporation into DNA was determined at various times thereafter. The results showed that EE at 2.5 micrograms/day and PB (0.05%) caused a rapid increase in liver DNA synthesis which peaked between 24 and 72 h and remained elevated for at least the next 7 days. Dose-response experiments with EE- and M-treated rats demonstrated that 24 h after beginning treatment, significant increases in liver DNA synthesis could be detected at an EE dose as low as 0.1 microgram/day; DNA synthesis was also significantly increased by M. The anti-estrogen tamoxifen (T), did not cause increased liver DNA synthesis. However, T at 15 micrograms/day did inhibit the induction of DNA synthesis caused by EE and M at 2.5 micrograms/day but not by PB (0.05%). The effect of T on promotion by EE of the appearance of gamma glutamyl transpeptidase (GGT)-positive foci was determined. Female SD rats were initiated with a single i.p. dose of diethylnitrosamine at 20 mg/kg given 24 h after partial hepatectomy. One week later the rats were treated with EE (5 micrograms/day), T (15 or 50 micrograms/day) or EE plus T at both doses using timed-release tablets. The rats were killed after 4 months and the incidence, number and size of the GGT foci determined. The results revealed that, as expected, EE enhanced the appearance of GGT foci. Unexpectedly, T alone at both doses also enhanced the appearance of the foci.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2877751 TI - Standards and guidelines for cardiopulmonary resuscitation and emergency cardiac care. PMID- 2877752 TI - Acute myocardial infarction: state of the art. AB - The proper management of patients with acute myocardial infarction changes frequently as new data develop in this complex area. The present recommendations concerning the use of oxygen and morphine and the treatment of hypotension and congestive heart failure require little change save the addition of new agents. However, considerable new data have been derived in the area of limitation of myocardial infarct size. Several studies suggest that the early administration of beta-blockers or intravenous nitroglycerin may benefit patients with acute infarction. We must seriously consider whether the data supporting the use of these agents justify a recommendation that they be used routinely for patients with acute infarction. The role of thrombolytic agents, although widely used already, must also be addressed as data supporting its use build. Additionally, there are suggestive data that the aggressive treatment of hypertension is beneficial, and this approach may well merit advocacy. The prophylactic use of lidocaine and the ubiquitous use of nitrates necessitate reevaluation, although presently both agents are widely used. The aggressive use of electrical therapy for supraventricular arrhythmias and the lack of indication for the treatment of asymptomatic bradycardia with atropine in patients with acute infarction must be added to the previous National Conference standards. PMID- 2877753 TI - Cardiovascular pharmacology. II: The use of catecholamines, pressor agents, digitalis, and corticosteroids in CPR and emergency cardiac care. AB - The Cardiovascular Pharmacology II panel met during the AHA National Conference on Standards and Guidelines for CPR and emergency cardiac care to consider the use of catecholamines, pressor agents, digitalis, and corticosteroids during advanced cardiac life support. During cardiac arrest, catecholamines and pressor agents have been shown to improve the rate of success of resuscitation. The useful properties of these drugs are mediated by strong alpha-adrenergic stimulation resulting in improved coronary perfusion. beta-Adrenergic stimulation during cardiac arrest is unimportant for resuscitation and potentially harmful. Studies have not demonstrated a difference between mixed agonists and alpha agonists with respect to overall outcome. Consequently, the panel recommended that epinephrine continue to be the primary vasopressor for use during cardiac arrest. For cardiovascular support in the hemodynamically unstable patient, the panel recommended that drugs be chosen for specific pharmacologic actions that will allow the needed physiologic manipulation guided by objective hemodynamic measurements. The panel found that digitalis preparations and corticosteroids have very limited use in emergency cardiac care. PMID- 2877754 TI - Cardiovascular pharmacology. III: Atropine, calcium, calcium blockers, and beta blockers. AB - Atropine, calcium, calcium-channel blockers, beta-adrenergic-receptor blockers, oxygen, morphine, vasodilators, and potent diuretics are frequently used in advanced cardiac life support (ACLS). Since the last AHA conference on ACLS standards, little controversy has arisen regarding the use of oxygen, morphine, vasodilators, or potent diuretics. In 1979, a full vagolytic dose of atropine was recommended for use early in the course of asystolic or bradycardiac arrest. Since then reports suggest that this higher dose of atropine may be of some limited value in treating this highly resistant form of arrest. The routine use of calcium for asystole, bradycardiac arrest, and electromechanical dissociation has come under intense scrutiny. Studies have failed to demonstrate improved survival and have found potentially deleterious levels of serum calcium when calcium was administered according to AHA standards. It is also possible that postanoxic cerebral injury is exacerbated by the use of calcium. No controversy exists, however, concerning the use of calcium for the moribund patient with possible hypocalcemia or with an excess of calcium-channel blockers. The use of calcium-channel blockers has been advocated to prevent or retard the intracellular accumulation of calcium, which may cause irreversible postanoxic tissue damage. Calcium-channel blockers may also be useful in preventing or decreasing cerebral and coronary arteriospasm. These drugs have antianginal properties that may decrease ischemia. The antiarrhythmic effect of verapamil is particularly useful in the treatment of uncomplicated paroxysmal supraventricular tachycardia. Verapamil and diltiazem slow conduction through the atrioventricular node and may be used to slow the ventricular response in atrial fibrillation and flutter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877755 TI - Effect of oral colchicine on T cell subsets, monocytes and concanavalin A-induced suppressor cell function in asthmatic patients. AB - Asthmatic patients have a deficiency of concanavalin A-(Con A) induced suppressor cell function. We tested whether oral colchicine 0.5 mg twice daily for 7 days could correct this immunoregulatory abnormality. Peripheral blood mononuclear cells were incubated with Con A and then suppression of proliferation was measured by coculture of these cells with healthy volunteers' mononuclear cells and phytohaemagglutinin. Sixteen asthmatic patients had significantly (P less than 0.002) decreased Con A-induced suppressor cell function (17.0 +/- 17.2%, mean +/- s.d.) as compared to 13 healthy volunteers (37.9 +/- 14.9%). Oral colchicine significantly (P less than 0.05) increased, though only partially corrected, these 16 asthmatic patients' Con A-induced suppressor cell function (28.1 +/- 14.3%). Asthmatic patients had an increased number of monocytes (691 +/ 289 vs 388 +/- 271/mm3 for normals, P less than 0.01) and a normal number of lymphocytes, Leu 4+ total T cells, Leu 3+ helper/inducer T cells, and Leu 2+ suppressor/cytotoxic T cells as well as a normal Leu 3/Leu 2 ratio. Oral colchicine significantly (P less than 0.005) decreased the number of monocytes (451 +/- 255/mm3) without significantly affecting the number of lymphocytes, Leu 4+, Leu 3+, or Leu 2+ T cells, or the Leu 3/Leu 2 ratio. These results are consistent with the hypothesis that the deficiency of Con A-induced suppressor cell function in asthmatic patients may be due, in part, to an increased number and/or abnormal activity of monocytes. If so, then oral colchicine may have partially corrected the deficiency of Con A-induced suppressor cell function by decreasing the number and/or modulating the activity of monocytes. PMID- 2877756 TI - Choice of immunoglobulin G purification method in assays for antibodies to the thyrotropin receptor. AB - Activity of autoantibodies to the thyrotropin receptor in the serum of patients with active Graves's disease was compared when the patients' IgG was purified by three different procedures: ammonium sulfate precipitation (I), a modified batch diethylaminoethyl cellulose method (II), and affinity chromatography on Protein A Sepharose CL-4B (III). IgG extracted by I was significantly less potent in inhibiting binding of 125I-labeled thyroid membranes than that prepared by either II or III, and was significantly less effective than II in stimulating adenyl cyclase activity in thyroid membrane. Thyroglobulin, a serum protein whose concentration is increased in patients with various thyroid diseases, was coprecipitated in amounts sufficient to significantly inhibit binding only when method I was used, but not with either of the other two procedures. Evidently method I is inferior to either of the other two when used for purification of autoantibodies to the thyrotropin receptor. Method II used in this study, being faster and more economical than I and of equivalent efficacy, is a feasible alternative method for clinical use. PMID- 2877757 TI - Identification of inhibitors of urinary alanine aminopeptidase. AB - Amino acids and ammonia were identified as natural inhibitors of urinary AAP. In urines from healthy volunteers approximately one half of the inhibition could be accounted for by amino acids and ammonia. At the measured concentrations, histidine, ammonia and phenylalanine, in decreasing order, were the most effective inhibitors. Results from kinetic studies with amino acids added to gel filtered urine are consistent with the presence of two AAP isoenzymes with different inhibition characteristics. The ten amino acids which were tested show the same inhibition kinetics. Differences between amino acids are quantitative. PMID- 2877758 TI - Serum and urinary enzyme activities in renal artery embolism. AB - Renal artery embolism is not a rare occurrence, especially in patients with valvular heart disease, but the early diagnosis of this condition is infrequently accomplished. We report the clinical and laboratory data of 2 patients with valvular heart disease who presented with unilateral renal artery embolization. The usefulness of the determination of serum and urinary enzymes and renal function tests is discussed. We propose that these parameters support an earlier and more accurate diagnosis of renal artery embolism. PMID- 2877760 TI - Increased levels of urinary adenosine deaminase binding protein in children treated with cisplatin or methotrexate. AB - Levels of adenosine deaminase binding protein (ABP), a renal tubular cell antigen, were determined by enzyme immunoassay in urine specimens from seven children with solid tumors who were receiving the recognized nephrotoxins cisplatin or methotrexate. ABP excretion was uniformly increased within the first 3 days after administration of either drug. Elevated ABP levels were usually accompanied by increased excretion of the urinary enzymes N-acetyl-beta-D glucosaminidase and alanine aminopeptidase. In alkaline urine specimens associated with methotrexate therapy, ABP levels were increased whereas enzyme activities appeared to be unstable. Hence, immunochemical measurement of urinary ABP levels may be adjunctively useful for clinical studies of renal tubular damage. PMID- 2877759 TI - Urinary enzyme excretion after a single dose of phenacetin and paracetamol (acetaminophen) during antidiuresis and during water diuresis. AB - 2 g phenacetin or paracetamol in a single oral dose were administered to five healthy persons under the conditions of antidiuresis and subsequent water diuresis. Excretion of the brush border enzyme GGT, the cytoplasm enzyme LDH, and the lysosomal enzymes, NAG and GAL, was analysed before, during and after ingestion of the analgesics. Increased excretion of LDH and GGT indicated a similar moderate damage of the tubular epithelia after phenacetin and paracetamol. The state of diuresis appeared to have no influence. PMID- 2877761 TI - Value of enzyme determinations in urine for the diagnosis of nephrotoxicity in rats. AB - Excretion of urinary lactate dehydrogenase (LDH, EC 1.1.1.27), gamma glutamyltransferase (gamma-GT, EC 2.3.2.2), alkaline phosphatase (ALP, EC 3.1.3.1), alanine aminopeptidase (AAP, EC 3.4.11.-), alanine aminotransferase (GPT, EC 2.6.1.2) and N-acetyl-beta-D-glucosaminidase (NAG, EC 3.2.1.30) was studied following a single i.v. application of 1 mg mercuric chloride/kg body weight or a radio contrast medium (SH H 340 AB) at a dose of 7.5 g iodine/kg body weight in rats. Measurements of urinary enzymes and serum urea nitrogen and creatinine were carried out on the second, third, fourth and ninth days after treatment. Histological examinations of kidneys were performed on day 9. A drastic increase in urinary LDH and moderate increase in gamma-GT, ALP and AAP and a very slight increase in GPT was observed in the first 18-h urine samples after mercuric chloride. This increase in enzymuria was associated with a drastic increase in serum urea nitrogen and creatinine, with a maximum on day 4. The radio contrast medium-treated animals showed a similar but less pronounced pattern of urinary enzymes excretion and only a slight increase of serum urea nitrogen on day 2. A good correlation was found between histological findings and enzymuria as well as serum urea nitrogen and creatinine. Thus, determination of only some urinary enzymes (LDH and gamma-GT) is valuable in predicting early nephrotoxicity and sufficient for the diagnosis of proximal tubule damage in rats. PMID- 2877762 TI - Adult T cell leukaemia/lymphoma. AB - Adult T cell leukaemia/lymphoma was first identified by Japanese investigators in the mid 1970s. Distinctive characteristics include hypercalcaemia, metabolic bone disease, opportunistic infections and evidence of multiorgan involvement. The malignant cell has the surface phenotype of a T helper lymphocyte but functions as a T suppressor cell, and in leukaemic patients this cell usually has a unique multilobed appearance, which may aid in recognizing the disease. The overwhelming majority of patients with ATLL originate from the south-west Japanese archipelago, as well as the Caribbean basin and south-east USA. The geographic localization of this disease is the result of the endemic distribution of the human retrovirus (HTLV-I) which has been established as the cause of ATLL. Infection with this virus may result in no disease (asymptomatic carriers) or ATLL. While ATLL usually pursues an acute or subacute (prototypic) course, patients are also seen with 'chronic' or 'smouldering' disease. Over time, these more indolent variations may progress to the prototypic form. When aggressive, ATLL must be treated with intense combinations of cytotoxic drugs similar to those used to treat the more common B cell lymphoproliferative disorders. Even though half of the patients treated achieve a remission, the duration is usually brief and the overall actuarial median survival is only 11 months. In addition to recurrent disease, these patients frequently succumb to opportunistic infections. PMID- 2877763 TI - Of mice and men: the extension of animal models to the clinical evaluation of new drugs. PMID- 2877764 TI - Use of beta blockers in congestive heart failure. PMID- 2877765 TI - Treatment of depression in the elderly. PMID- 2877766 TI - Clinical aspects of insomnia. PMID- 2877767 TI - Schizophrenia and antipsychotic drugs. AB - A variety of effective drugs are available for the treatment of schizophrenia. Knowledge of the side-effect spectrum of the various classes of antipsychotic drugs is necessary for the clinician to arrive at a rational choice of medication. In general, the preferred drug will be a high-potency neuroleptic. The following basic principles of clinical psychopharmacology should be followed: Consider risk and benefits; clinical experience is prerequisite; establish the diagnosis; select the appropriate class of psychotropic drug for the primary diagnosis; within drug class, the drugs are usually equally effective for patients with the diagnosis; give a dose that is high enough to be effective; choose target symptoms that can be monitored to indicate when to stop or increase the drug; avoid use of multiple drugs when possible; drugs are only one element in a comprehensive treatment strategy. Other modalities need equally careful consideration, e.g., psychotherapy, group therapy, family treatment, and vocational rehabilitation; and consultation with other subspecialists should be sought readily when indicated. PMID- 2877768 TI - Management of anxiety in the elderly. AB - Clinicians need to be aware of the cardinal manifestations of clinical anxiety in their geriatric patients. A variety of psychotherapeutic, behavioral, and chemical interventions can effectively and safely treat anxiety in geriatric patients and thereby greatly diminish morbidity and mortality. PMID- 2877769 TI - Clinical and neurobiologic implications of antipsychotic-induced movement disorders. PMID- 2877770 TI - The pathway of glutamate oxidation in isolated mitochondria from the avian hepatomatous growth induced by MC-29 virus. AB - The mitochondria isolated from transplantable chicken hepatomatous growth induced by MC-29 virus were deficient in glutamate dehydrogenase. Oxypolarographic tests showed that glutamate oxidation in the tumor mitochondria was initiated via transamination, while glutamate was deaminated by glutamate dehydrogenase in liver mitochondria to supply adenosine triphosphate. Prominent glutamate oxidation and transformation-linked low glutamine synthetase activity may be favorable to the bioenergetics of this fast-growing tumor. PMID- 2877771 TI - Acetate metabolism by tissues of the rabbit. AB - Acetyl CoA synthetase (E.C.6.2.1.1) and acetyl CoA hydrolase (E.C.3.1.2.1) activities were assayed in sub-cellular fractions of rabbit liver, heart and kidney homogenates. The intracellular location of acetyl CoA hydrolase was predominantly mitochondrial in all tissues, whereas that for acetyl CoA synthetase varied between the tissues studied. The relationship between location of enzyme activity and metabolism of acetate in different tissues is discussed. PMID- 2877772 TI - Interaction of lead toxicity and riboflavin status in chicks (Gallus domesticus). AB - Chicks (Gallus domesticus) were fed diets containing 0 or 2000 ppm lead (Pb) and adequate, marginal or deficient levels of riboflavin. In comparison to adequate, marginal riboflavin depressed growth at 2000 ppm Pb but not at 0 ppm Pb. Deficient riboflavin depressed growth at both Pb levels, and Pb depressed growth at all riboflavin levels. Hepatic glutathione reductase activity was reduced by riboflavin deficiency, but Pb was without effect. Hepatic non-protein sulfhydryl concentrations were increased by Pb, and the increases were greater at the lower riboflavin levels. Dietary Pb appears to increase the level of riboflavin required in chick diets. PMID- 2877774 TI - Chronic ethanol intake in lactating rats: milk analysis. AB - Milk was analyzed at 5 and 15 days of lactation in rats fed an ethanol liquid diet or appropriate control diet. Alcoholic rats showed blood ethanol levels as high as 43 mM at the end of lactation. Milk from ethanol-fed rats showed an increase in pH, protein and lipids and a decrease in lactose, compared with controls. Chronic ethanol consumption seems to reduce the yield of milk. The nutritional status of sucklings from alcoholic mothers seems to be related more to the quantity of milk than to its quality. PMID- 2877773 TI - Enzymatic activity in crude oil contaminated rats. AB - The activity of enzymes found in the plasma, malate dehydrogenase (MDH) and lactate dehydrogenase (LDH), and enzymes from erythrocytes, glucose-6-phosphate dehydrogenase (G-6-PDH) and catalase, was studied in rats contaminated by crude oil. Crude oil (tube fed) contamination caused a significant increase in MDH and LDH activity 96 hr after contamination while a decrease in activity was noted in 6-6-PDH and catalase. An additional contamination (1 week after the first contamination), measured 96 hr after contamination, caused a relative decrease in MDH and LDH activity while there was a contrasting relative increase in G-6-PDH and catalase activity. After a recovery period of 3 weeks the only significant change was an increase in catalase activity. PMID- 2877775 TI - The induction of alpha 1-acid glycoprotein by methylmercury. AB - The incorporation of [14C]leucine into protein was measured in liver preparations and blood of rats following the s.c. administration of methylmercury hydroxide (24 mg/kg body wt) or turpentine (5.0 ml/kg body wt). The translatability of the RNA obtained from polysomes in an mRNA-dependent reticulocyte lysate was elevated significantly in the preparations derived from the treated rats compared to control rats. Immunoprecipitation of the labelled translation products or of serum proteins showed that the mRNA activity and the synthesis of alpha 1-acid glycoprotein, an acute phase reactant, was elevated by the methylmercury treatment as well as by the turpentine-induced inflammatory response. PMID- 2877776 TI - Selective activation of carcinogenic aromatic amines to bacterial mutagens in the marine mussel Mytilus galloprovincialis. AB - The postmitochondrial fraction of the marine mussel Mytilus galloprovincialis digestive gland activates selectively precarcinogenic aromatic amines, but not precarcinogenic benzo[a]pyrene, to Salmonella typhimurium TA 98 mutagens. This activation potential is NADPH-dependent, is not inducible by exposure to Diesel 2 oil and a polluted environment, and is inhibited by methimazole. The characteristics of this activation potential are consistent with the recent finding of the presence of FAD-containing-, and lack of cytochrome P-450 dependent-, monooxygenase activity in Mytilus edulis. The presence of such selective potential in marine invertebrate(s) may bring new insight into our understanding of the fate and the effects of carcinogens in the marine environment. PMID- 2877777 TI - A comparative survey of the type of sympathetic neuro-melanophore transmission in catfishes. AB - The types of innervation to integumental melanophores were surveyed comparatively within the order Siluriformes. In fish or many families, pigment aggregation within melanophores was found to be under the control of adrenergic sympathetic postganglionic fibers as in other fish. In silurid catfish, on the other hand, the cells were found to be regulated cholinergically, though the fibers concerned were sympathetic postganglionic. Muscarinic cholinoceptors mediate the melanin aggregating response. In some catfish belonging to Bagridae, Pimelodidae and Callichthyidae, the melanophores strangely possessed cholinoceptors, notwithstanding the fact that they were under adrenergic nervous control. These results were discussed in conjunction with the phylogeny of Siluriformes. PMID- 2877778 TI - Mixed function oxidase activity in the harbour seal (Phoca vitulina) from Sable Is., N.S. AB - One adult male, eight pups (including two full term foetuses) and nine adult female harbour seals (Phoca vitulina) were analysed for indices of mixed function oxidase (MFO) activity. MFO activity was present in liver samples, but was at or below detection limits in samples of kidney, lung and pancreas. Hepatic ethoxyresorufin O-de-ethylase and benzo[a]pyrene hydroxylase activities were similar to those reported in other seals and in other mammals. Cytochromes P-450 and b5 concentrations were slightly lower than those observed in other mammals. MFO activities in newborn pups and foetuses were significantly lower than those in adult females. No qualitative differences in cytochrome P-450 isozyme distribution between foetal and adult samples could be discerned by electrophoresis. PMID- 2877779 TI - Active peptides in the skins of two hundred and thirty American amphibian species. AB - Extracts prepared from dried or fresh skins of more than 200 American amphibian species were subjected to biological screening in order to determine occurrence and contents of peptides active on smooth muscle preparations, systemic blood pressure and, subordinately, external secretions, anterior pituitary and the central nervous system. The peptide families identified in skin extracts were as follows: caruleins (caerulein, phyllocaerulein), tachykinins (physalaemin, phyllomedusin), bombesins (phyllolitorin, [Leu8]phyllolitorin, rohdeilitorin), bradykinins (phyllokinin and others), sauvagine, dermorphins (dermorphin, [Hyp6]dermorphin), tryptophyllins (numerous peptides) and, finally, miscellaneous peptides. None of the above peptide families showed a widespread distribution, but all were restricted to particular amphibian genera or stocks. The hylid frogs of the Phyllomedusinae family occupy a unique position, as their skin displayed the greatest variety and abundance of active peptides ever found in any amphibian is destined to increase because numerous other peptide molecules await isolation, elucidation of structure and definition of possible biological activities. PMID- 2877780 TI - Indole-, imidazole- and phenyl-alkylamines in the skin of one hundred and forty American amphibian species other than bufonids. AB - Extracts prepared from dried or fresh skins of 140 American amphibian species, other than bufonids, were subjected to chemical and biological screening in order to determine the presence and concentrations of aromatic biogenic amines. The most frequent and abundantly occurring amine category was that of indolealkylamines, represented by their prototype 5-hydroxytryptamine and its N methylated derivatives. Conjugated and cyclized indolealkylamines, typical for the toad skin, were apparently lacking. Phenylalkylamines were represented by two quaternary ammonium bases: leptodactyline and, very rarely, candicine. Leptodactyline was particularly abundant in leptodactylid frogs of the genus Leptodactylus. Histamine occurred in trace amounts in different species, in large amounts only in some Leptodactylus species of the "pachypus" section. On the other hand, N-methylated histamines and cyclized histamines (spinaceamines) were confined to the skin of Leptodactylus pentadactylus labyrinthicus. The possible taxonomical and evolutionary significance of amphibian skin amines is pointed out. PMID- 2877782 TI - Extraction and identification of different prostaglandins in Allium cepa. AB - Green onions (Allium cepa) were homogenized in a blender and extracted by normal extraction methods except that diethyl ether was used as the first extracting solvent. Different analytical procedures were used for the identification of the prostaglandins separated. TLC was applied using silica gel 60 F254 plates and a mixture of benzene, dioxane and acetic acid (20:10:1) as eluent, and the Rf values were compared with those of authentic samples. GC analysis on an SE 30 packed column and FID was applied; relative retention times of the onion extract components were measured and matched with authentic prostaglandin samples using cholesterol as an internal standard. GC-MS analyses using the same conditions adopted for GC analysis were conducted on a Finnigan MAT 112S instrument. Four peaks were identified. The prostaglandins identified were F1 alpha, E1, B1 and A2. PMID- 2877781 TI - The uptake and metabolism of L-glutamate by tissue slices of the cestode Hymenolepis diminuta. AB - The in vitro uptake of L-[3H]glutamate by tissue slices of the cestode Hymenolepis diminuta, denuded of tegument, was investigated. Two sodium concentration-dependent mechanisms, one of high affinity (Kt 1.8 X 10(-5) M; Vmax 4.76 pMoles/min/mg wet weight) and another of low affinity (Kt 2.2 X 10(-4) M; Vmax 50.7 pMoles/min/mg wet weight), were identified, in addition to a sodium insensitive component. Exchange of preloaded [3H]glutamate did not occur in tissue slices incubated in dilute unlabelled glutamate. Acidic amino acids, imipramine and fluoxetine were effective inhibitors of high and low affinity uptake, while glutamate receptor ligands, neurotransmitters and some antihelminthics generally were not. The concentrations present in, and the metabolism of glutamate by, tissue slices was examined by HPLC. The significance of the three modes of glutamate uptake and their possible role in the physiology of H. diminuta are discussed. PMID- 2877783 TI - Studies of Zn, Mg, Cu, Ca and Fe in cadmium poisoned toads before and after treatment with EDTA. AB - Zn, Mg, Cu, Ca and Fe were determined spectrophotometrically in liver, kidneys, muscle, spleen and blood of Bufo regularis after a single i.m. injection of 6.2 mg Cd/kg (which represents the 96 hr LD50) alone or in combination with 40 mg EDTA/kg (the minimal EDTA concentration causing 100% survival over that period). Cadmium administration caused recognizable effects on the essential metals levels in different tissues and organs. In the majority of the tissues and organs studied, zinc and copper concentrations returned to their normal ranges in animals that received both cadmium and EDTA. In contrast, magnesium, calcium and iron contents not only returned back to their control values but also exceeded them. PMID- 2877784 TI - Caffeine and ephedrine stimulated thermogenesis in LA-corpulent rats. AB - Resting metabolic rate (RMR), as well as caffeine (CAF) and ephedrine (EPH) stimulated thermogenesis (VO2) were measured in young adult corpulent (corp) LA/N cp (LA-corpulent) rats. RMR of lean was greater than corp. Administration of EPH, CAF and EPH + CAF resulted in 32, 48 and 50% increases in VO2, respectively, in both lean and corp rats. The time to attain maximal VO2 was similar for both drugs in both phenotypes, but the duration of maximal VO2 averaged 50, 26 and 42% longer in corp than lean for EPH, CAF and EPH + CAF, respectively. Acute weight loss following these treatments was greater for corp than lean, and corresponded with the duration of elevated VO2. These results are consistent with a normally functioning end-organ sympathomimetic receptor system in the corp phenotype of the LA/N-cp rat, and suggest that obesity in this model may be caused by factors other than defective brown fat thermogenesis at the end organ level. PMID- 2877785 TI - Comparative study of the edema-forming activity of Costa Rican snake venoms and its neutralization by a polyvalent antivenom. AB - The edema-forming activity of eight Costa Rican crotaline snake venoms and its neutralization by a polyvalent antivenom were studied using the mouse footpad test. All of the venoms induced edema, the highest activity being present in the venoms of Bothrops lateralis and Bothrops picadoi. When experiments were performed with preincubation of venom and antivenom, neutralization of edema was poor. Moreover, it was observed that, with some venoms, edema increased when large doses of antivenom were used. This effect was also observed when some venoms were incubated with coral snake antivenom, suggesting that venoms may release some pharmacologically active component(s) from antivenom, since the latter contains traces of alpha-2 and beta globulins. Based on these findings, an alternative approach to the study of the neutralization of edema was used; in this new method, antivenom was injected i.v. before venom administration, thereby avoiding preincubation. With this technique, a much better neutralization of edema was observed, although with some venoms it was still poor. Venoms contain low molecular weight factors which induce edema, suggesting that lack of immunogenicity of some components may cause a poor neutralization. However, such components are responsible for only a minor portion of the edema induced by crude venoms. It is suggested that experiments in which venom and antivenom are preincubated preincubated in testing the neutralization of edema should be avoided, and that a more adequate approach may be an independent inoculation of venom and antivenom. PMID- 2877786 TI - The effect of sub-lethal doses of dieldrin on the ventilatory and cardiac activity in two species of shrimps. AB - The effect of dieldrin on the heart and ventilatory activity in the shrimps Macrobranchium faustinum and Macrobrachium amazonicum was studied over 4 and 7 day exposure periods, respectively. In M. faustinum, ventilatory rate increased by 43% and heart rate by 14.4%. In M. amazonicum, the ventilatory and heart rates decreased by 21 and 6%, respectively. In M. amazonicum ventilatory reversal frequency, an index of respiratory stress, was 6.7 times higher than the control values. All the changes, except for M. amazonicum heart rate were significant at the 0.01 level of probability. PMID- 2877787 TI - The effect of sub-lethal doses of dieldrin on resting and active metabolism in two species of shrimps. AB - The effects of dieldrin on the active (VaO2) and resting (VrO2) oxygen consumption rates of the shrimps Macrobrachium faustinum (De Sassure) and Macrobrachium amazonicum (Heller) were studied during exposure for 4 days at 0.01 p.p.b. and 7 days at 0.0002 p.p.b., respectively. The VrO2 of M. faustinum increased significantly (P less than 0.01) by 48% but the VaO2 decreased by 13%. The VrO2 and VaO2 decreased by 43 and 70%, respectively, in M. amazonicum. Thus, in both species the aerobic metabolic scope for activity decreased. The increased resting metabolic rate of the indigenous M. faustinum is ascribed to energy consuming responses which allow compensation for the effects of the stressor. The stressor may be said to have moved this species into a metabolic "zone of compensation". The decreased resting metabolic rate of the pond-cultured M. amazonicum is ascribed to greater susceptibility, more extensive metabolic breakdown and failure of compensatory responses. This species might be said to have been forced by the stressor into a metabolic "zone of collapse". PMID- 2877788 TI - Effects of different doses of cyproterone acetate (CA) on preputial gland structure and activity in intact male mice. AB - The preputial is an androgen-dependent structure which appears to be used in pheromonal signalling in rats and mice. The structure of representative glands from intact oil injected male laboratory TO strain mice was contrasted with tissue from intact counterparts treated with the anti-androgen cyproterone acetate (CA). Sixteen days of an i.m. application of a modest range of CA doses (0.5, 1.0 and 2.0 mg/day given as oily solutions) and a variety of control treatments were used to assess influences on the structure and function of the preputial. The glands of intact male mice treated with oil were well-developed and actively secreting with parenchymatous acini at different stages of maturation. Such glands are generally highly Sudanophilic, with the lipophilic stain concentrated in acini in frozen sections and many acini are compressed by their neighbours to assume irregular shapes. Wax and frozen preputial sections from intact subjects treated with 0.5 or 1.0 mg CA were, in contrast, less well developed and had fewer and smaller lipid droplets. Treatment of counterparts with 2 mg CA reduced acinar number and diameter in both wax and frozen sections with a concomitant increase in the proportion of connective tissue. The data confirm that this anti-androgen antagonizes the androgen secreted by the testis and adrenal cortex in terms of its expression of function on the preputial gland. These data provide further evidence that cyproterone acetate's suppressive actions on murine aggression are primarily via its ability to depress the secretion of odour cues that facilitate attack. PMID- 2877789 TI - The pharate adult clasper as a tool for measuring chitin synthesis and for identifying new chitin synthesis inhibitors. AB - A rapid, reliable, repeatable bioassay for measuring chitin synthesis is described. It utilizes the clasper from male pharate adult European corn borers and measures the incorporation of [14C]N-acetylglucosamine. Chitin synthesis is maximum in claspers taken from animals 5 and 6 days postpupation. The system is very sensitive to inhibition by the phenylbenzoyl ureas and polyoxins and should be useful for identifying potential inhibitory agents. PMID- 2877790 TI - Histamine and histamine receptors: behavioral thermoregulation in the salamander Necturus maculosus. AB - Low doses (0.01, 0.1 mg/kg, i.p.) of histamine (HA) caused selection of significantly lower temperatures, and higher doses (0.5, 1.0 mg/kg) increased temperatures by mudpuppies in linear thermal gradients. Injection of the HA precursor, L-histidine (500 mg/kg) produced an increase in the temperatures selected. Results from injections of HA H1-receptor agonist (2-pyridylethylamine) and antagonist (pyrilamine), and H2-receptor agonist (dimaprit) and antagonist (cimetidine) had significant effects on thermoregulation; H1-receptors may mediate behavioral hyperthermia and H2-receptors behavioral hypothermia. Responses to these histaminic compounds are significantly influenced by the time of day at which the responses are measured and by season and acclimation temperature. The equivalent behavioral responses in both endotherms and ectotherms to agents which produce physiological hyperthermia and hypothermia are probably behavioral hypothermia ("cold seeking") and behavioral hyperthermia ("heat seeking"), respectively. PMID- 2877791 TI - Pharmacology of FMRFamide in Mytilus catch muscle. AB - In the anterior byssus retractor muscle (ABRM) of Mytilus, low concentrations of FMRFamide (10(-8)-10(-7) M) relax ACh-induced catch-tension, whereas high concentrations (greater than 10(-7) M) cause contraction. To study the structure activity relations of these actions, a number of peptide analogs of FMRFamide were screened for their biological activities on the ABRM. The structure-activity relations for contraction were different from those for relaxation. Among the peptides tested, FMR-[D-Phe]-amide and gamma 1-MSH substantially antagonized FMRFamide contractions; but only gamma 1-MSH was even slightly antagonistic to FMRFamide-induced relaxation. Relaxations produced by 10(-7) M FMRFamide, or by 10(-5) M FMRFamide-relating relaxing peptides, were markedly depressed by treating the muscle first with 10(-5) M FMRFamide or with 10(-5) M FMRFamide related contractile peptides. However, contractile agents that are structurally unrelated to FMRFamide, such as 3 X 10(-5) M SCPB and 2 X 10(-2) M caffeine, showed little or no such after-effect on the relaxation. Relaxations in response to submaximal serotonin, dopamine and repetitive electrical pulses of stimulation were not affected by a pretreatment with 10(-5) M FMRFamide. These results suggest that the ABRM of Mytilus has at least two pharmacologically distinct classes of receptors which are capable of being activated by FMRFamide. PMID- 2877792 TI - Treatment with prostaglandins reduces the antifertility effect of indomethacin in rabbits. AB - Indomethacin (Id) treatment of rabbits at the time of implantation resulted in a significant reduction in the number of viable embryos as well as significant reduction in plasma progesterone concentrations. Treatment with a mixture of prostaglandins (PGs) together with Id caused a significant increase in both the number of viable embryos and in plasma progesterone concentrations when compared to the treatment with Id alone. The PG mixture used in the present study did not succeed in fully reversing the Id antifertility effect. PMID- 2877793 TI - Specific binding of Leu-enkephalin to small and large intestinal epithelial cells from guinea-pig. AB - Leu-enkephalin receptors were identified in guinea-pig intestinal mucosa in small as well as in large epithelial cells. Binding studies at apparent equilibrium could be interpreted in terms of two populations of receptors in every intestinal segment. Leu-enkephalin receptors were unequally distributed along the intestinal mucosa, with the lowest density but the highest affinity values in the caecum and colon. Duodenal epithelial cells exhibited the highest binding values due to a great number of low-affinity receptors. Receptors exhibited a high degree of specificity for Leu-enkephalin as evidenced by the poor competition shown by a variety of enkephalin analogues and naloxone and the lack of effect of other unrelated peptides present in the intestinal tract. PMID- 2877794 TI - Primary structure and synthesis of a blocked myotropic neuropeptide isolated from the cockroach, Leucophaea maderae. AB - A peptide which stimulates the contractile activity of the cockroach hindgut was isolated from head extracts of the cockroach, Leucophaea maderae. The inability of aminopeptidase M to degrade the peptide and the presence of glutamic acid in the hydrolysate suggested N-terminal blocking by pyroglutamic acid. The N terminal pGlu was removed enzymatically and the unblocked fragment was sequenced with an automated gas-phase peptide sequencer. The structure determined (pGlu-Thr Ser-Phe-Thr-Pro-Arg-Leu-NH2) was synthesized and shown to be both chemically and biologically identical with the natural product. PMID- 2877795 TI - Blockade of a putative GABA-mediated neurotransmission in the cerebellum by benzodiazepine receptor inverse agonists. AB - An exponential relationship was observed between the firing rate of cerebellar Purkinje cells in urethane-anaesthetized rats and the duration of inhibition evoked in these cells by electrical stimulation of the nearby cortical surface. Benzodiazepines, administered i.v., decreased cell firing and increased the duration of the inhibitory response but did not alter the relationship between the two parameters. These effects of one benzodiazepine, RU 32007, were reversed by the benzodiazepine antagonist Ro15-1788 which had little effect alone. The benzodiazepine inverse agonists methyl- or ethyl-beta-carboline-3-carboxylate increased cell firing with the expected reductions in duration of inhibitory response in some cases. However, in 50% of recordings the inhibitory response disappeared, independent of the firing rate. All the effects of the beta carboline esters were reversed by Ro15-1788 or the benzodiazepine, RU 32007. This action of the benzodiazepine receptor inverse agonists represents an in vivo blockade of an endogenous synaptic inhibition which is thought to be mediated by release of GABA. PMID- 2877796 TI - Histological and pharmacological investigations of the two symmetrically situated giant neurons, RPeNLN and LPeNLN, identified on the anterior surface of the pedal ganglia of an African giant snail (Achatina fulica Ferussac). AB - Morphological and pharmacological investigations were made of two giant neurons, RPeNLN (right pedal nerve large neuron) and LPeNLN (left pedal nerve large neuron), situated symmetrically on the anterior surface of the pedal ganglia of an African giant snail (Achatina fulica Ferussac). The two neurons (about 250-300 microns in diameter) were the largest ones identified in the ganglia of the snail species. The axonal pathways of the two neurons were symmetrical; of their four main axonal branches, the three main branches innervated the ipsilateral pedal nerves, whereas the last main branch projected to the contralateral pedal nerves. The pharmacological features of the two neurons were very similar. Both were inhibited markedly by dopamine [minimum effective concentrations (MECs): 3 X 10( 6)-10(-5) M], DL-octopamine (MECs: 2 X 10(-6)-2 X 10(-5) M), 5-hydroxytryptamine (MEC: 3 X 10(-6) M), GABA (MEC: 3 X 10(-4) M), L-homocysteic acid (MECs: 3 X 10( 5)-10(-4) M) and erythro-beta-hydroxy-L-glutamic acid (MEC: 3 X 10(-5) M). Acetylcholine showed varied effects, either excitatory or inhibitory, on the two neurons examined. No substances were found to have any marked excitatory effects on the neurons. PMID- 2877797 TI - Species variations in the relaxation of tail arteries to electrical stimulation. AB - Relaxation in response to electrical stimulation has been studied in isolated tail arteries from rats, cats and pigs. Electrical stimulation elicited contractile responses in unstimulated strips, but caused frequency-dependent relaxations in tail arteries from all species studied, following contractile responses by various agents. The order of susceptibility to the relaxant effect of electrical stimulation in arteries from all three species was pig greater than cat greater than rat. Relaxations to electrical stimulation were unaffected by prior treatment of arteries with atropine, propranolol, tetrodotoxin, indomethacin, ouabain, pyrilamine and chemical denervation with 6-hydroxy dopamine, but were prevented, dose-dependently, by cimetidine and aminophylline (antagonists of histamine H2-receptor and adenosine P1-receptor, respectively). The results suggest that relaxation of tail arteries from the rat, cat and pig in response to electrical stimulation is modulated by histamine and adenosine. PMID- 2877798 TI - Adenosine receptors mediate pigment dispersion in leucophores of the medaka, Oryzias latipes. AB - Using the medaka, Oryzias latipes (orange-red variety), the mechanisms of action on leucophores of adenosine and adenine nucleotides, including cyclic AMP, were studied. All these substances were found to be very effective in dispersing leucosomes. Their pigment-dispersing action was antagonized by methylxanthines. These substances did not aggregate leucosomes. It was concluded that leucophores possess specific binding sites for adenosine, i.e. adenosine receptors, on the cell membrane, which mediate leucosome dispersion. Further, it was shown that even the action of an established intracellular second messenger, cyclic AMP, is primarily manifested through the receptors. PMID- 2877799 TI - Toxicity of cadmium administration to the toad and the treatment of its poisoning with EDTA. AB - The effect of cadmium administration on female Bufo regularis was studied. The median lethal doses were 22, 18, 15 and 6.2 mg Cd2+/kg after 24, 48, 72 and 96 hr respectively. After a single intramuscular injection of 6.2 mg Cd2+/kg (representing 96-hr LD50), the results indicated that Cd2+ causes severe physiological abnormalities to this experimental animal. The serums alanine aminotransferase (AlAt), aspartate aminotransferase (AAt), alkaline phosphatase (AlP) and lactic dehydrogenase (LDH) were elevated while the calcium serum was not influenced by Cd2+ throughout the experimental period. On the other hand, phosphorus, total protein and total bilirubin were increased. EDTA treatment (0.2 mmole/kg) protected female toads from mortality up to 20 mg Cd2+/kg. It overcame the physiological alterations that were caused by the Cd2+ injection. This may be due to the fact that Cd2+ is bound to EDTA in a strong complex which is readily excreted via the kidneys. PMID- 2877800 TI - A note on eggshell porosity, nest humidity and the effects of DDE in the grey heron (Ardea cinerea). AB - Water vapour conductance (GH2O) was determined for 25 grey heron Ardea cinerea eggs in the laboratory, and in nests during natural incubation at two Scottish colonies. The mean GH2O of eggs measured in the nest which successfully hatched was 9.0 mgH2O/mmHg/day and the mean water vapour pressure gradient between egg and nest (delta PH2O), measured using "calibrated" duck eggs, averaged at 31 mmHg (4.13 kPa). Based on eggshell porosity results, from the eggs which hatched, such a gradient would result in a loss of water from the eggs during incubation equivalent to 11% of their fresh weight. Shell thickness, the number of pores/cm2 of eggshell and DDE content were also determined for the 25 eggs measured in the laboratory. Eggs containing high levels of DDE had thinner shells, more pores in the eggshell and a higher overall eggshell porosity. The main problem posed by a high level of DDE would appear, however, not to be an excessive water loss from the egg during incubation, but rather eggshell thinning leading to a loss of the egg due to breakage in the nest. PMID- 2877801 TI - Effect of ethylenediaminetetraacetic acid (EDTA) on acute mercury poisoning of toad. AB - Studies have been carried out on the ability of EDTA (CaNa2 ethylenediaminetetraacetate) to offset the acute toxicity of mercuric chloride. The lethality of mercury was tested in female Bufo regularis species (Amphibia) which were given EDTA immediately after the Hg2+ injection. The results show that the inherent toxicity of the EDTA-mercury complex is sufficiently high for it to be ineffective as an antidote. PMID- 2877802 TI - Differences between breeds of rabbits in their susceptibility to the effect of foschlor. AB - The purpose of the study was to investigate the effect of foschlor on erythrocytes and leucocytes in two breeds of rabbits--Belgian and black-and-tan. Administration of the pesticide caused a considerable drop in the number of erythrocytes, haemoglobin level and haematocrit value in both breeds. Changes in the values of red blood cell indices, characterized by an increase in mean erythrocyte volume and haemoglobin content in blood cells, were observed in the black-and-tan breed only. The pesticide used caused changes in leucocytes in both breeds, expressed as a distinct neutrophilic leucocytosis with lymphopaenia and eosinopaenia. Changes in the leucogram were reflected in the increase in the leucocyte index. The degree of intensity of the changes in both erythrocytes and leucocytes points to the greater resistance of the Belgian breed to intoxication by foschlor than the black-and-tan breed. PMID- 2877803 TI - Haematological changes in male and female pharaoh quails (Coturnix coturnix Pharaoh) after Ekatin intoxication. AB - The purpose of this study was to determine changes in the blood of pharaoh quails after Ekatin intoxication, to define the duration of disturbances caused by intoxication and to examine possible sex differences in the birds' reaction to intoxication. It was found that Ekatin reduced the number of erythrocytes, haemoglobin level and haematocrit value, increased erythroblast and reticulocyte numbers and increased the osmotic resistance of blood cells. It was shown that this pesticide caused neutrophilic leucocytosis with lymphopaenia and eosinopaenia. In males changes in the blood appeared far earlier than in females and they underwent compensation earlier, that is, 3 weeks after intoxication the majority of the haemotological parameters reached values similar to the control. PMID- 2877805 TI - Clastogenic effects of five carcinogenic-mutagenic chemicals on the cells of the common carp, Cyprinus carpio L. AB - The cytogenetic effects of various i.p. treatments with five carcinogenic mutagenic chemicals and three doses for each (aflatoxin B1, Aroclor 1254, benzidine, benzo[a]pyrene and 20-methylcholanthrene), were investigated in the cells of the common carp, Cyprinus carpio. Injection with distilled water and corn oil served as the two control groups. For detecting cytogenetic damage we used two test systems, chromosomal aberrations (CA) in kidney cells and micronucleated erythrocytes (M). At 48 hr after treatment with the chemicals under investigation, the frequencies of CA and M were clearly increased in a dose response manner compared to the control groups. PMID- 2877804 TI - Effects of barium on isolated frog spinal cord. AB - The effects of Ba2+ were studied in vitro on the isolated frog spinal cord. Ba2+ (25 microM-5 mM) caused a concentration-dependent depolarization of ventral (VR) and dorsal (DR) roots. TTX and Mg2+ substantially reduced the depolarization suggesting that interneuronal effects were involved. Ba2+ (25-500 microM) markedly increased the frequency and duration of spontaneous VR and DR potentials and substantially enhanced the duration (and frequently the amplitude) of VR and DR potentials evoked by DR stimulation. Higher concentrations of Ba2+ (1-5 mM) reduced both spontaneous and evoked potentials. Ba2+ (25-500 microM) enhanced the amount of K+ released by a DR volley and by application of L-glutamate and L aspartate. The cation reduced VR and DR root depolarizations produced by elevated [K+]0. VR potentials induced by L-glutamate, L-aspartate, GABA and glycine and DR depolarizations caused by GABA were reduced by Ba2+. These results show that Ba2+ has complex actions on reflex transmission, interneuronal activity, the postsynaptic actions of excitatory and inhibitory amino acids and the evoked release of K+. PMID- 2877806 TI - Motility of isolated mammalian gastric fundus. AB - Gastric fundus strips (GFS) of rats, guinea-pigs, rabbits, cats and humans, but not of dogs, show spontaneous phasic contractions in vitro. Rabbit, cat, dog and human GFS exhibit dose-dependent responses to acetylcholine (ACh), histamine (His), serotonin (5-HT) and KCl. Guinea-pig drug-induced responses are not dose dependent. Rat GFS does not respond to His. ED50S for KCl are always higher than for other agonists. ED50S for 5-HT are lower than for other drugs in rats and cats, but not different in other species. Maximal GFS contractions induced by ACh are usually higher than those induced by other drugs. PMID- 2877807 TI - A behavioral role for enkephalins in regulating locomotor activity in the insect Leucophaea maderae: evidence for high affinity kappa-like opioid binding sites. AB - D'-Ala-2 met-5-enkephalinamide application to the cerebral ganglia of Leucophaea maderae results in a decrease in locomotor activity. The opiate antagonist, naloxone, can block this effect as well as the depressant effect of morphine on locomotor activity. D-Ala-2,leu-5-enkephalinamide and dynorphin enhance locomotor activity following their topical application to the cerebral ganglia. This effect also can be antagonized by concomitant naloxone treatment. Benzomorphans were the most potent ligands tested in their ability to displace [3H]D'-ala-2,met-5 enkephalinamide whereas mu and delta ligands were by comparison less potent. These results suggest the presence of kappa-like opioid receptors in Leucophaea cerebral ganglia. The kappa ligands also are potent in enhancing locomotor activity in addition to being weakly antagonized by naloxone. Again, these results indicate the presence of multiple-opiate receptor types in invertebrates. PMID- 2877808 TI - The use of the chelating agent EDTA in the treatment of acute cadmium toxicity, tissue distribution and some blood parameters in the Egyptian toad Bufo regularis. AB - Erythrocyte count, haemoglobin content, haematocrit value, erythrocyte sedimentation rate and cadmium accumulation in some organs and tissues were estimated in toads administered 6.2 mg Cd2+/kg i.m. for 4 days. EDTA therapy caused considerable decrease in all the blood parameters studied. A striking reduction in the cadmium content of all the organs and tissues studied except the kidneys was also observed after simultaneous treatment with EDTA. PMID- 2877809 TI - Noninducibility of cytochrome P-450 in the earthworm Dendrobaena veneta. AB - Cytochrome P-450 has been measured in the earthworm Dendrobaena veneta (Rosa) in a direct spectrophotometric procedure. The P-450 was found not in the dense microsomal fraction, but in the less dense overlying fraction often referred to as buffy coat. Earthworm P-450 was not induced by 3-methylcholanthrene or phenobarbitol. PMID- 2877810 TI - Cyclic nucleotide action is mediated through adenosine receptors in damselfish motile iridophores. AB - Effects of cyclic nucleotides on motile iridophores were examined in the blue damselfish, Chrysiptera cyanea. All of the cyclic nucleotides tested, i.e. cAMP, 2',3'-cAMP and cGMP, accelerated the clearing response of the cells even at concentrations of 10(-5) or 10(-4) M. The action of these nucleotides was effectively antagonized by methylxanthines. These results suggest that the effect of cyclic nucleotides on damselfish iridophores is mediated by adenosine receptors in a similar fashion to the action of adenosine. PMID- 2877811 TI - Ontogenetic study of the regulatory and coupling function of guanyl nucleotide binding proteins in the hormone-sensitive adenylate cyclase system. AB - Reconstitution of catecholamine-sensitive adenylate cyclase from chick embryonic muscle membranes and guanyl nucleotide-binding proteins of mature rabbit muscle makes it possible to reveal the coupling (potentiating) effect of these nucleotides 1 week earlier than in the native condition. The effective insertion of guanyl-nucleotide-binding proteins into the embryonic membrane coincides with the onset of a pronounced increase in membrane lipid fluidity during the course of embryogenesis. The different ontogenetic time-courses for the origination of the two guanyl nucleotide effects, on catalytic adenylate cyclase activity (in early embryogenesis) and on the coupling process (in postembryonic life), suggest the existence in this system of two separate guanyl-nucleotide-binding proteins performing regulatory and coupling functions, respectively. PMID- 2877812 TI - Acute epiglottitis in the adult. AB - Acute epiglottitis in the adult is uncommon. This case reports a young man with acute epiglottitis secondary to a Bacteroides melanogenicus supraglottic abscess. This pathogen has not been previously described as being causitive of epiglottitis. PMID- 2877813 TI - A polymorphic human myosin heavy chain locus is linked to an anonymous single copy locus (D17S1) at 17p13. AB - Restriction fragment length polymorphisms (RFLPs) have been developed for an adult human skeletal muscle myosin heavy chain gene which was previously mapped to the short arm of human chromosome 17. Using RFLP analysis of DNA from 140 individuals, we have found tight linkage (LOD score of 6.9) between this myosin heavy chain gene and the anonymous DNA probe, D17S1. PMID- 2877815 TI - [Multiple endocrine neoplasias--MEN type I and II--the clinical picture, diagnostic and surgical-therapeutic strategy]. PMID- 2877814 TI - Percutaneous transluminal angioplasty of right and left internal mammary artery grafts. AB - Four patients with recurrent severe angina and evidence of myocardial ischemia two to six months after surgical coronary revascularization have been submitted to percutaneous transluminal angioplasty of the distal insertion of internal mammary artery grafts or of the recipient vessel distal to it. These cases illustrate the feasibility and safety of transluminal angioplasty of right and left internal mammary artery grafts, using the mammary artery as a way of access. PMID- 2877816 TI - [Insulinomas and rare endocrine tumors]. PMID- 2877817 TI - Extrahepatic glucuronidation of morphine in the dog. AB - The pharmacokinetic disposition of morphine was studied in sham-operated dogs, dogs with hepatic devascularization, and dogs with bile duct and ureter ligation after iv administration of 1 mg/kg of morphine. In sham-operated dogs, morphine is rapidly distributed and eliminated, with a terminal half-life of 65 +/- 30 min. Morphine glucuronide appeared in plasma within 5 min and rose rapidly to levels an order of magnitude higher than morphine levels, before both declined in parallel. In hepatic devascularized dogs, there was a marked delay in morphine elimination due to a 47% reduction in clearance. The appearance of morphine glucuronide in plasma was not delayed, but the AUC of morphine glucuronide was reduced by 56% compared to control for the first 180 min. In bile duct- and ureter-ligated dogs, elimination of morphine was increased and morphine glucuronide elimination from plasma was decreased, suggesting that glucuronide normally excreted in bile is hydrolyzed back to the parent compound and reabsorbed in sham-operated control animals. In conclusion, morphine was glucuronidated by both hepatic and extrahepatic glucuronyltransferases to an approximately equal extent in the dog. PMID- 2877818 TI - Metabolism of tracazolate. Metabolites in dog and rat urine. AB - The urinary metabolites of tracazolate [4-n-butylamino-1-ethyl-6-methyl-1H pyrazolo (3,4-b) pyridine-5-carboxylic acid ethyl ester], an anxiolytic agent, obtained from rats and dogs dosed with 14C-labeled tracazolate have been characterized. No unchanged tracazolate was detected. Fifteen metabolites were identified in dog urine, seven of which had not previously been found in rat blood and tissue. Eleven of these metabolites were also found in rat urine. The metabolites were formed by deesterification to the 5-carboxylic acid; N deethylation of the pyrazole ring: oxidation at the gamma-position of the n butylamino side chain; oxidation of the terminal carbon of this side chain; loss of the n-butylamino group; and hydroxylation of the 6-methyl group followed by condensation with the 5-carboxylic acid to form gamma-lactones. The major metabolites in dog urine were the desethyl-desbutyl-deesterified compound, the desbutyl-deesterified compound, and the desbutyl-desethyl-lactone. Loss of the butyl side chain and, also, lactone formation, appeared to occur to a lesser extent in the rat than in the dog. PMID- 2877819 TI - Epidermis: the major site of cutaneous benzo(a)pyrene and benzo(a)pyrene 7,8-diol metabolism in neonatal BALB/c mice. AB - The metabolism of benzo(a)pyrene (BP) and benzo(a)pyrene-7,8-diol (BP-7,8-diol) by microsomes prepared from whole skin, dermis, and epidermis of neonatal BALB/c mice pretreated with topically applied 3-methylcholanthrene (MCA) was compared. In control animals, microsomes prepared from epidermis showed higher rates of metabolism of BP and BP-7,8-diol (1.4-2.6-fold) than did microsomes prepared from whole skin or dermis. A single topical application of MCA increased the rate of metabolism of BP and BP-7,8-diol in microsomes prepared from whole skin, dermis, and epidermis. The greatest increase occurred in the epidermis. The in vivo covalent binding of [3H]BP, [3H]BP-7,8-diol, and 7,12 [3H]dimethylbenz(a)anthracene ([3H]DMBA) to DNA was found to be greater in epidermis (8.7-15.4-fold) than in whole skin or in dermis. A single topical application of MCA to BALB/c mice enhanced the in vivo binding of [3H]BP, [3H]BP 7,8-diol and [3H]DMBA to DNA of whole skin, dermis, and epidermis more than 2 fold. Exposure of Salmonella tester strains TA98 and TA100 to 2-aminoanthracene, a skin carcinogen, in the presence of an epidermal metabolic activation mixture resulted in a greater mutagenic response when compared to activation mixtures derived from whole skin or dermis. These results indicate that epidermis is the major site of polycyclic aromatic hydrocarbon metabolism and of enzyme-mediated covalent binding of polycyclic aromatic hydrocarbon carcinogens to DNA in skin of BALB/c mice and that topically applied MCA has maximum enzyme induction effects in this skin compartment. PMID- 2877820 TI - Identification of the enzymes catalyzing metabolism of methoxyflurane. AB - The hepatic microsomal metabolism of methoxyflurane in rabbits is markedly stimulated by treatment with phenobarbital. However, the increased rate of metabolism cannot be completely accounted for by the activity of the purified phenobarbital-inducible cytochrome P-450 isozyme 2, even in the presence of cytochrome b5. The discovery of a second hepatic phenobarbital-inducible cytochrome P-450, isozyme 5, led us to undertake experiments to determine in hepatic and pulmonary preparations the portion of microsomal metabolism of methoxyflurane catalyzed by cytochrome P-450 isozymes 2 and 5. We report herein that isozyme 2 accounts for 25% and 29%, respectively, of the O-demethylation of methoxyflurane in hepatic microsomes from untreated and phenobarbital-treated rabbits, and for 25% of the methoxyflurane metabolism in pulmonary microsomes. Results for isozyme 5 indicate that it catalyzes 19% and 27% of methoxyflurane metabolism in control and phenobarbital-induced liver, and 47% of O-demethylation in the lung. In summary, we demonstrate that methoxyflurane O-demethylation in lung, phenobarbital-induced liver, and control liver microsomes is catalyzed by cytochrome P-450 isozymes 2 and 5. Results with purified cytochrome P-450 isozyme 5 are consistent with those obtained using microsomal preparations. Furthermore, metabolism of methoxyflurane by purified isozyme 5 is markedly stimulated by cytochrome b5. A role for cytochrome b5 in cytochrome P-450 isozyme 5-catalyzed metabolism of methoxyflurane was also demonstrated in microsomes. Antibody to isozyme 5 was unable to inhibit methoxyflurane metabolism in the presence of maximally inhibiting concentrations of cytochrome b5 antibody.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877821 TI - Comparative effects of H2-receptor antagonists on drug interaction in rats. AB - The most widely used H2-receptor antagonist, cimetidine, is known to interact with cytochrome P-450 drug-metabolizing enzymes and, therefore, interacts with other drugs which may be administered concurrently. In this study, effects of three H2-receptor antagonists, famotidine, ranitidine, and L-643,441, on drug interaction were studied using cimetidine as a positive control. Cimetidine and L 643,441, but not famotidine or ranitidine, prolonged antipyrine elimination and hexobarbital-induced sleeping time. The effect of cimetidine and famotidine on the anticoagulant effect on warfarin in rats was also investigated. Pretreatment of rats with cimetidine produced a significant depression of plasma prothrombin complex activity, whereas concomitant administration of famotidine did not alter the plasma prothrombin complex activity. Whereas cimetidine is known to impair the elimination of a number of drugs metabolized by microsomal mixed function oxidase enzyme systems, the results of the present study suggest that famotidine and ranitidine have little effect on these enzyme systems. PMID- 2877822 TI - The metabolic fate of stiripentol in man. AB - The metabolism of stiripentol (I), a new antiepileptic drug, was studied in healthy human subjects. Following a single 1200-mg oral dose to one subject, 13 metabolites of I were detected in urine and were identified by GC/MS techniques. The structures of 9 of these metabolites were confirmed subsequently by synthesis of the corresponding reference compounds. The nature of the urinary metabolites of I revealed the operation of five distinct metabolic pathways for this drug, viz. conjugation with glucuronic acid, oxidative cleavage of the methylenedioxy ring system, O-methylation of catechol metabolites, hydroxylation of the t-butyl group, and conversion of the allylic alcohol side-chain to the isomeric 3 pentanone structure. Metabolites of I excreted into urine over 12 hr accounted for the majority (73%) of an acute dose, whereas a further 18% was recovered in feces as the unchanged drug. These findings suggested that the search for additional metabolites would yield only trace amounts. From a quantitative standpoint, the most important pathway of biotransformation of I following both acute and chronic dosing involved opening of the methylenedioxy ring to generate catechol derivatives. This finding probably accounts for the known inhibitory effects of I on the oxidative metabolism of other antiepileptic agents and for the clinically significant drug interactions involving stiripentol. PMID- 2877824 TI - Oxidative and defluorinative metabolism of fludalanine, 2-2H-3-fluoro-D-alanine. AB - The antibacterial agent fludalanine [2-2H-3-fluoro-D-alanine (DFA)] is a potent inhibitor of bacterial alanine racemase, an enzyme required for the generation of D-alanine, an essential component of the bacterial cell wall. Primary metabolism of DFA involves its oxidation to fluoropyruvate (FP); this organic fluoride is then rapidly reduced to fluorolactate (FL) which is the major organic metabolite in laboratory animals. Gas-liquid chromatographic chemical ionization mass spectrometric assays were developed for these two metabolites. FL is the predominant organofluoride metabolite of DFA in the circulation. FP was detected in the urine although recovery was very low. The rapid conversion of FP to FL precludes assay of the former in serum. Maximum serum FL concentrations in the rat appear about 1 hr after the dose of DFA and are relatively constant for several hours thereafter. The peak FL concentration is proportional to the dose of DFA; repeated daily dosing of DFA appears to cause neither saturation nor induction of metabolic pathways. Comparison of FL concentrations determined using the GC/MS assay with those based on an enzymic method specific for L-(+)-FL demonstrated that only the latter isomer is found in the plasma of monkeys dosed with DFA. In vivo exchange studies involving the alpha-proton of FL indicate that a small FP pool exists and is in equilibrium with FL. A crude pyruvate dehydrogenase complex isolated from beef heart mitochondria was shown to produce equimolar quantities of acetate, CO2, and fluoride from FP. PMID- 2877823 TI - Relationship between changes in seromucoid concentrations and the rate of oxidation or acetylation of several substrates. AB - This study was carried out to assess the relationship between turpentine-induced elevation of seromucoids and drug metabolism. Six groups of rats were used; one of them received 1 ml of turpentine sc, another received 1 ml of turpentine by gavage (po), and a third group received, ip, 80 mg/kg of phenobarbital daily for 3 days. Three control groups received saline instead of turpentine. Forty-eight hr later, the serum seromucoids were assayed and the rates of N-demethylation of aminopyrine, O-dealkylation of 7-ethoxycoumarin, and hydroxylation of aniline and total cytochrome were determined in liver microsomes. When turpentine was administered sc, seromucoids increased from 3.15 +/- 0.18 to 16.13 +/- 0.84 g/dl (mean +/- SE) (p less than 0.01), but the rates of N-demethylation (p less than 0.01), of O-dealkylation (p less than 0.01) and of hydroxylation (p less than 0.05) were all decreased. In the rats receiving turpentine po, seromucoids remained unchanged, but the rates of N-demethylation and O-dealkylation as well as the concentration of total cytochrome increased (p less than 0.01). Phenobarbital enhanced significantly the rates of N-demethylation, O dealkylation, and hydroxylation and the total concentration of cytochrome, without modifying the concentration of seromucoids. In another set of experiments we assessed whether turpentine-induced inflammation would affect the in vivo rate of acetylation of sulfamethazine; the results show that inflammation does not affect the rate of acetylation, despite an important increase in seromucoids. It is concluded that, under the present experimental conditions, there is no direct relationship between changes in seromucoids and the rate of drug metabolism. PMID- 2877825 TI - An overfed rat model that reproduces acetaminophen disposition in obese humans. AB - This disposition of acetaminophen was examined in an overfed rat model of human obesity following iv administration of a subtoxic 303 +/- 5 mg/kg dose based upon ideal body weight. Weanling Sprague-Dawley rats were maintained on a nutritionally complete semisynthetic diet containing 60% vegetable shortening and were compared to animals given a standard laboratory diet over the same 22-week period. At the time of study obese rats outweighed controls by 42% (637 +/- 32 g vs. 450 +/- 7 g, respectively). The absolute clearance of acetaminophen from plasma increased by 27% in obese rats. Higher partial formation clearance to acetaminophen glucuronide and sulfate conjugates accounted for most of this increase. Clearance by sulfhydryl conjugation was also substantially increased (56%), indicating that metabolism via toxic oxidation also occurred at a greater rate in obese animals. Absolute renal clearance of the glucuronide and sulfate conjugates but not acetaminophen increased with obesity, whereas parent volume of distribution remained unchanged. Some rats raised on the energy-dense diet remained lean and were examined separately as a dietary control group. Acetaminophen disposition in these animals was indistinguishable from pellet-fed controls, suggesting that acetaminophen elimination changes in overweight animals resulted from obesity itself and not from the obesity inducing energy-dense diet. Although animals placed on the energy-dense diet ate fewer grams of food per day, their caloric intake was similar to that of pellet-fed animals when adjusted for differences in body weight and caloric content of the diets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877826 TI - Mouse liver thiol methyltransferase. Assay conditions, biochemical properties, and strain variation. AB - Thiol methyltransferase (TMT) catalyzes the S-methylation of aliphatic sulfhydryl drugs and xenobiotic compounds. It would be useful if there were an experimental animal model in which the regulation and function of TMT could be studied. Therefore, TMT activity was measured in hepatic microsomes from A/J mice. Substrate kinetics for mouse liver microsomal TMT, like those for the enzyme in human red blood cell membranes and human kidney microsomes, were biphasic, with apparent "high" and "low" affinity forms of TMT with 2-mercaptoethanol as the methyl acceptor substrate. Apparent Michaelis (Km) constants of the high and low affinity activities for 2-mercaptoethanol were 30 microM and 12 mM, respectively. Apparent Km values of the high and low affinity activities for S-adenosyl-L methionine, the methyl donor for the reaction, were 47 microM and 61 microM, respectively. The optimal pH for the high affinity activity was between 7.2 and 8.1, whereas the optimal pH for the low affinity activity was approximately 9.2. Differential centrifugation showed that more than 85% of both activities was associated with membrane fractions. SKF 525A, a potent inhibitor of TMT in human tissues, inhibited mouse liver high and low affinity TMT activities by 88% and 46%, respectively, at a concentration of 0.5 mM. TMT activities were then measured in hepatic microsomes from nine additional inbred strains of mice. High affinity TMT activities varied 1.7-fold, whereas low affinity activities varied 2.1-fold among these strains. Since the properties of TMT in mouse liver are similar to those of the enzyme in human tissue, the inbred mouse will be a useful experimental animal model in which to study the regulation and function of TMT. PMID- 2877827 TI - Use of the NIH shift to determine the relative contribution of competing pathways of aniline metabolism in the rat. AB - The retention of tritium in urinary p-aminophenol and p-hydroxyacetanilide was determined following the administration of p-3H-aniline or p-3H-acetanilide to rats. When p-3H-aniline (1.5 mmol/kg, ip) was given to rats, the retention of tritium in urinary p-aminophenol and p-hydroxyacetanilide was 15% and 38%, respectively. Similar results were obtained following the administration of p-3H acetanilide (1.5 mmol/kg). However, when p-3H-acetanilide was given to rats which had been pretreated with bis-(p-nitrophenyl)phosphate to block the deacetylation capacity, urinary 3H-p-hydroxyacetanilide was recovered with 53% retention of tritium. The data indicate that, at the doses studied: the primary route of aniline metabolism is via sequential acetylation and hydroxylation, and deacetylation plays a significant role in the disposition of acetanilide. PMID- 2877828 TI - Pharmacokinetics of bupropion and metabolites in plasma and brain of rats, mice, and guinea pigs. AB - Recent reports indicate that bupropion, a novel non-tricyclic antidepressant, is metabolized differently in certain species of animals. To further define the disposition of bupropion, a study was done involving three species, the rat, mouse, and guinea pig, as animal models to evaluate bupropion metabolism. The pharmacokinetic profiles of bupropion and its major basic metabolites, BW 306U and BW A494U, were determined following the ip administration of 40 mg/kg bupropion to these animals. Pharmacokinetic profiles of the parent drug and metabolites from plasma and brain samples were obtained using a liquid chromatographic procedure. Further investigation of the reduced bupropion metabolite BW A494U was carried out by the ip administration of this metabolite to these animals and assaying the plasma and brain samples 90 min after dosing. Analysis of the pharmacokinetic data revealed that the rat quickly metabolized bupropion, but no basic metabolites accumulated. The mouse metabolized bupropion predominantly to BW 306U, whereas the guinea pig converted bupropion to reduced bupropion (BW A494U) as well as BW 306U. Brain/plasma ratios of bupropion among these animals did not vary significantly. However, both metabolites showed dramatic differences in their brain/plasma ratios among these species. When reduced bupropion (BW A494U) was injected, almost 3% of the plasma concentration of BW A494U was determined to be bupropion in the rat. Lesser amounts were converted in the mouse and guinea pig. Therefore, we have demonstrated that distinct differences exist in the metabolism of bupropion in various species of animals. The guinea pig, when compared to the rat or mouse, appears to constitute a model that most closely resembles that of human bupropion metabolism. PMID- 2877829 TI - Nonenzymatic isomerization of all-trans- and 13-cis-retinoids catalyzed by sulfhydryl groups. AB - Certain thiol-containing compounds catalyze, in a chemical reaction, the isomerization of all-trans-retinoic acid (RA) to 13-cis-RA and of 13-cis-RA to RA. Reactions approaching equilibrium contain more RA than 13-cis-RA. Small molecules effective as catalysts are glutathione, mercaptoethanol, and L-cysteine methyl ester. L-Cysteine is not a catalyst and inhibits the reaction catalyzed by glutathione or mercaptoethanol. Apoferritin (a thiol-containing protein), native microsomes, and, to a lesser extent, boiled microsomes catalyze the reaction, but their activity is reduced or eliminated by prior incubation with iodoacetate. Other cis and trans isomeric retinoids are also substrates for this reaction; the reactions proceed more readily for the cis isomers. The thiol-catalyzed isomerization of RA and 13-cis-RA may account for the observations of both cis and trans forms of retinoids in tissues of animals after administration of either. PMID- 2877830 TI - The metabolic disposition of laudanosine in dog, rabbit, and man. AB - This paper summarizes the results of studies of the metabolic fate of laudanosine, a major degradation product of atracurium. Intravenous bolus doses of laudanosine (1-3 mg/kg) were administered to eight dogs and two rabbits anesthetized with halothane, and urine and bile samples were collected for up to 6 hr. Urine samples also were collected from two surgical patients given repetitive doses of atracurium. Metabolites were isolated from all samples using C18-Sep Paks. Treatment of the isolates with beta-glucuronidase followed by purification of the hydrolysate by preparative liquid chromatography provided metabolite fractions which were characterized by analytical liquid chromatography and capillary gas chromatography combined with nitrogen-phosphorus and/or electron ionization-mass spectrometric detection. Reference compounds were employed as chromatographic retention time markers. O-Trimethylsilyl, O-tert butyldimethylsilyl, and N-trifluoroacetyl derivatives of the metabolites and reference compounds were used for gas chromatographic and mass spectrometric analysis. In all three species, the following metabolites of laudanosine were identified: pseudocodamine (4'-desmethyllaudanosine), pseudolaudanine (6 desmethyllaudanosine), laudanine (3'-desmethyllaudanosine), codamine (7 desmethyllaudanosine), N-norlaudanosine, N-norpseudocodamine, and N norpseudolaudanine. PMID- 2877831 TI - Immunohistochemical evidence for alterations in specific forms of rat hepatic microsomal cytochrome P-450 during acute carbon tetrachloride intoxication. AB - The response of specific forms of hepatic microsomal cytochrome P-450 to carbon tetrachloride was studied by immunohistochemical techniques in order to assess the localization and specificity of action for this hepatotoxin. Liver sections were taken from control, phenobarbital-pretreated, and 3-methylcholanthrene pretreated male rats that had received acute (3 hr) treatment with carbon tetrachloride. The liver sections were examined after indirect immunofluorescent labeling with anti-P-450un, anti-P-450a, anti-P-450b, and anti-P-450c. Diminished fluorescence and loss of intracellular homogeneity of fluorescence were found in the centrilobular cells of liver sections from control rats incubated with anti-P 450un, anti-P-450a, and phenobarbital-pretreated, carbon tetrachloride-challenged rats incubated with anti-P-450b. In liver sections from 3-methylcholanthrene pretreated, carbon tetrachloride-challenged rats incubated with anti-P-450c, fluorescence was diminished in periportal cells but did not show loss of intracellular homogeneity. These results provide immunohistochemical evidence for the differential effect of carbon tetrachloride on specific forms of cytochrome P 450. PMID- 2877832 TI - N-(4-hydroxyphenyl)-all-trans-retinamide pharmacokinetics in female rats and mice. AB - The distribution of N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR) and its metabolites was investigated in the liver, serum, mammary gland, and urinary bladder of female rats and mice. Following an iv dose of 5 mg/kg to rats, 4-HPR distributed to all tissues examined with the highest levels reached in the liver. The distribution period was completed in about 4 hr and was followed by first order elimination kinetics. The t1/2 for 4-HPR elimination from the liver was 9.4 hr, from the serum was 12.0 hr (not significantly different from liver), from the mammary gland was 43.6 hr, and from the urinary bladder was 9.3 hr. A 5-day ip dosing study (5 mg/kg/day of 4-HPR) in both rats and mice revealed that 4-HPR distributed to all tissues examined with the highest levels reached in the urinary bladder. 4-HPR and four metabolites were detected in the tissues. One coeluted with a cis isomer of 4-HPR (M2), another with N-(4-methoxyphenyl)-all trans-retinamide (4-MPR) (M3), a third appeared to be a 4-HPR-ester (M4), and the fourth remains unidentified (M1). However, the amount of each metabolite varied between tissues and between species. The concentration of 4-HPR was significantly 2-4 times lower and the percentage of M3 (4-MPR) was 3 times higher in the mouse tissues than in the corresponding tissues of the rat. M2 (cis-4-HPR) and M4 (4 HPR-ester) were present in rat liver but not in mouse liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877833 TI - Disposition of ethimizol, a nootropic drug, in rats and mice. AB - The pharmacokinetics of ethimizol, a nootropic drug, were studied in rats and mice using [2-14C]-4,5-di(methylcarbamoyl)-1-ethyl-imidazole. Autoradiography in mice injected iv showed a rapid and homogeneous distribution of the label into the tissues, brain included, and its excretion by the urinary pathway. The determination of ethimizol in plasma, organs, and excreta was based on combined extraction and the TLC procedure. In rats, the elimination half-life of ethimizol after iv administration of 10 mg/kg was 25 min, and its distribution volume was 1.4 liters/kg. The tissue/plasma concentration ratio for organs investigated was 1 immediately after iv administration, with a subsequent gradual increase. Based on this, saturable tissue binding of ethimizol in the liver, kidney, and brain was suggested. The drug was almost completely absorbed after administration, yet its systemic availability was only 32%. The brain uptake index of ethimizol was 101% as compared to 3H2O. Ethimizol was eliminated by metabolism. The labeled metabolites were predominantly excreted in the urine. PMID- 2877834 TI - Metabolism of 2,6-dimethylnaphthalene by rat liver microsomes and effect of its administration on glutathione depletion in vivo. AB - Metabolism of the environmental contaminant 2,6-dimethylnaphthalene (2,6-DMN) by rat liver microsomes and an NADPH-regenerating system led to the formation of three ring oxidation metabolites--2,6-dimethyl-3-naphthol, 2,6-dimethyl-3,4 naphthoquinone, and 3,4-dihydro-3,4-dihydroxy-2,6-dimethylnaphthalene--and one side chain oxidation metabolite--2-hydroxymethyl-6-methylnaphthalene. In addition, one metabolite remained unidentified. Pretreatment of rats with phenobarbital, 3-methylcholanthrene, Prudhoe Bay crude oil, or 2,6-DMN enhanced the rate of microsomal metabolism of 2,6-DMN 2-6-fold and significantly altered the metabolite profile. Liver microsomes from variously pretreated rats also enhanced the irreversible binding of 2,6-DMN[8-14C]N to microsomal protein. This binding to protein was inhibited by glutathione in a concentration-dependent manner. In vivo administration of 2,6-DMN to untreated rats led to a time dependent depletion of hepatic glutathione levels. Both the rate and the extent of glutathione depletion were significantly enhanced in 3-methylcholanthrene pretreated rats but not in phenobarbital-pretreated rats. PMID- 2877835 TI - Tissue levels and biological effects of N-nitrosodimethylamine in mice during chronic low or high dose exposure with or without ethanol. AB - In a study of the metabolism, disposition, and hepatotoxicity of the environmental carcinogen N-nitrosodimethylamine (NDMA), as a function of dose in the drinking water and of concomitant administration of ethanol, outbred Swiss mice were given NDMA for 1-4 weeks at levels of 50-0.5 ppm, with or without 10, 20, or 30% ethanol. NDMA, assayed in blood, liver, kidney, lung, and brain by thermal energy analysis after methylene chloride extraction, was detectable (greater than 0.5 ppb) in tissues of the mice after all doses of NDMA. The 0.5 ppm dose yielded tissue levels of NDMA (1-4 ppb) near the detection limit of 0.5 ppb; this was also found to be the minimal concentration causing significant numbers of lung tumors in strain A mice after treatment for 16-18 weeks. Co administration of ethanol caused an increase in blood and tissue levels of NDMA at all levels of both chemicals, often by a factor of 10 or more. Ethanol also partially alleviated the morphological hepatotoxic effects of NDMA at 50 ppm (centrilobular hemorrhage and necrosis). These results are consistent with competitive inhibition of metabolic activation of NDMA by ethanol. Ten per cent ethanol did not induce liver NDMA demethylase activity significantly and did not prevent loss of this activity from the livers of mice receiving 5-50 ppm NDMA. Thus, inhibition, rather than induction, of NDMA metabolism was the predominant effect of ethanol, with increased levels of NDMA in blood and other tissues as a consequence. PMID- 2877836 TI - Hopantenic acid beta-glucoside as a new urinary metabolite of calcium hopantenate in dogs. AB - The metabolism of calcium hopantenate (HOPA) was studied in beagle dogs. After oral administration of 14C-labeled HOPA, 25.5% of the administered radioactivity was excreted in the urine within 24 hr, mostly in the form of unchanged drug. The only metabolite, accounting for 4.2% of the radioactivity in the urine, was isolated by HPLC. The metabolite was hydrolyzed by the treatment of beta glucuronidase (Helix pomatia), acid phosphatase, or beta-glucosidase. These enzyme activities were not inhibited by treatment with D-glucaric acid 1,4 lactone or PO4(3-), but with D-gluconic acid 1,5-lactone, demonstrating that the metabolite is a glucose conjugate. The compound was identified as HOPA-glucoside, 4'-O-(beta-D-glucopyranosyl)-D-hopantenic acid, by GC/MS analyses after derivatization of the metabolite and the synthetic compound. This is the first reported instance of glucose conjugation to a non-acidic hydroxyl group in the metabolism of xenobiotics in mammals. PMID- 2877838 TI - Bidirectional cross-tolerance between methadone (mu)- and ethylketocyclazocine (kappa)-tolerant rats. AB - Our laboratory previously reported on unidirectional cross-tolerance between morphine and methadone, both mu opioid agonists, and between morphine and ethylketocyclazocine (EKC), the latter being a relatively selective kappa opioid agonist. Morphine-tolerant rats were found to be non-cross-tolerant to methadone and EKC, but methadone- and EKC-tolerant rats were cross tolerant to morphine. In the present study, we characterized the cross-tolerance between methadone and EKC. A group of female adult Sprague-Dawley rats was made tolerant to methadone by a series of automatic i.v. injections ranging from 0.25 mg/kg per 2 h on the first day to 2.0 mg/kg per 1.5 h on the ninth day. Another group of rats was similarly made tolerant to EKC with doses ranging from 0.5 mg/kg per 2 h on the first day to 4 mg/kg per h on the ninth day. Relatively similar degrees of tolerance development to the EEG and behavioral effects of methadone and EKC were reflected by decreases in durations of action and decreases in opioid-induced EEG power spectral changes. Methadone-tolerant rats were found to be cross-tolerant to the EEG and behavioral effects of EKC, and, similarly, EKC-tolerant rats were found to be cross-tolerant to those of methadone. Thus, a bidirectional cross tolerance between a mu and a kappa agonist was demonstrated. The present results together with those reported earlier indicate that cross-tolerance may not be directly related to the receptor selectivity of the opioids. It is possible that differential physicochemical properties of these opioids may play a more decisive role in the phenomenon of cross-tolerance. PMID- 2877837 TI - A proton magnetic resonance study of the metabolism of N-methylformamide in the rat. PMID- 2877839 TI - Subjective effects of khat chewing in humans. AB - The subjective effects of Khat (Catha edulis) chewing were studied in 14 male somali, habitual khat users, by means of the Addiction Research Center Inventory (ARCI) questionnaire and of visual analogue scales concerning mood and appetite. Results show that euphoria, improved intellectual efficiency and alertness were associated with khat consumption in 10 subjects. In contrast, the remaining 4 subjects experienced only dysphoria and mild sedation. These latter effects were present in all the subjects in the post-chewing period. In spite of these subjective differences, blood pressure and pulse rate increased in all the volunteers studied. As a whole, these results are consistent with the presumed amphetamine-like action of khat, but suggest also a major role of environmental factors in the expression of these actions. PMID- 2877840 TI - Effect of ethanol on the spontaneous transmitter release by nerve endings in the process of maturation. AB - Ethanol stimulates the spontaneous transmitter release from motor nerve endings, as shown by the increase of miniature end plate potential (m.e.p.p.) frequency at the neuro-muscular junction. The stimulation of acetylcholine spontaneous quantal release by ethanol is greater in regenerating than in mature nerve endings. The different effects of ethanol on regenerating nerve endings may be related to changes of chemical-physical membrane properties. PMID- 2877841 TI - The effects of (+/-)-methylenedioxymethamphetamine and (+/-) methylenedioxyamphetamine in monkeys trained to discriminate (+)-amphetamine from saline. AB - Recently, attention has been focused on (+/-)-methylenedioxymethamphetamine (MDMA), a psychotomimetic agent chemically closely related to the psychomotor stimulant methamphetamine, and also to the hallucinogen mescaline. In the present experiment, the effects of MDMA and (+/-)-3,4-methylenedioxyamphetamine (MDA) were determined in rhesus monkeys that were trained to discriminate intravenously administered (+)-amphetamine (AMPH) from saline in a two-lever, food-maintained paradigm or to discriminate intragastrically administered AMPH from saline in a signalled electric shock avoidance paradigm. MDMA produced 100% drug-appropriate responding in all six monkeys, regardless of the procedure and route of administration while MDA substituted completely for AMPH in only two of three monkeys in each paradigm. The results suggest that MDMA has subjective effects that are similar to those of AMPH while MDA is somewhat less like AMPH. PMID- 2877842 TI - Self-administration of methylenedioxymethamphetamine (MDMA) by rhesus monkeys. AB - Four rhesus monkeys trained to press levers for intravenous cocaine infusions were tested with saline and (+/-)-3,4-methylenedioxymethamphetamine (MDMA; 3-300 micrograms/kg per infusion) during daily 1-h sessions. From four to over nine times more cocaine infusions were obtained than saline infusions during baseline sessions. When MDMA was substituted for cocaine, at least one dose was self administered in 3 of the 4 monkeys at rates that exceeded the range of saline infusions. In fact, two of the monkeys self-administered a dose of MDMA at a greater rate than cocaine. These results demonstrate that MDMA can serve as a positive reinforcer for rhesus monkeys and, taken together with other preclinical behavioral studies, suggest a potential for recreational use of MDMA by humans. PMID- 2877844 TI - [Somatostatin--is this still indicated in ulcer bleeding?]. PMID- 2877843 TI - Discriminative stimulus properties of (+/-)-3,4-methylenedioxymethamphetamine and (+/-)-3,4-methylenedioxyamphetamine in pigeons. AB - Pigeons trained to discriminate (+)-amphetamine (AMPH) from saline in a two-key food-maintained drug discrimination paradigm, were used to investigate the discriminative stimulus (DS) effects of two structural analogues of amphetamine, namely (+/-)-3,4-methylenedioxymethamphetamine (MDMA) and (+/-)-3,4 methylenedioxyamphetamine (MDA). After discrimination performance was stable (90% injection-appropriate responding), test sessions with various doses of AMPH were conducted and a dose-dependent relationship for AMPH-appropriate responding was obtained. Both MDMA (3.0 mg/kg) and MDA (3.0 or 5.6 mg/kg) substituted for AMPH; however, at these doses MDA produced a greater decrease in response rate compared to AMPH and MDMA. Furthermore, while MDMA and MDA were similar in potency in producing drug-appropriate responding, both were less potent than AMPH. These results indicate that MDMA and MDA have DS effects similar to AMPH in pigeons. PMID- 2877845 TI - [Pediatric cryptorchism]. PMID- 2877848 TI - Symposium on enteric-coated sulphasalazine in rheumatoid arthritis. Proceedings of a symposium. London, December 6, 1985. PMID- 2877846 TI - The effects of antihypertensive drugs on serum lipids and lipoproteins. II. Non diuretic drugs. AB - This review examines the effects of various antihypertensive drugs on blood lipids, lipoproteins, and apolipoproteins. A large number of studies have documented the elevation of total cholesterol, triglycerides, low density lipoprotein (LDL) cholesterol, and very-low density lipoprotein (VLDL) cholesterol with many thiazide-type diuretic drugs, albeit mainly in short term studies. When added to thiazide diuretics, both beta 1-selective and non selective beta-blocking drugs elevate total triglycerides and VLDL triglycerides, lower high density lipoprotein (HDL) cholesterol and raise the ratio of total cholesterol to HDL cholesterol ratio. Most non-selective beta-blockers have similar effects when used as monotherapy, but the beta 1-selective agents appear not to affect HDL cholesterol in monotherapy. Prazosin appears free of adverse lipid effects and has improved lipid-lipoprotein concentrations in many studies. Preliminary data on several other drugs also suggest a favourable lipid profile and additional study is warranted - among these are guanabenz, clonidine, pindolol, labetalol, indapamide, and guanfacine. Elevations in serum triglycerides are often ignored on various counts, but triglycerides have been found to be a strong risk factor in European studies and in women over the age of 50 years in the Framingham study. Despite the unfavourable short term effects of diuretics, the theoretical risk of the lipid-lipoprotein changes remains unclear because HDL cholesterol and the total cholesterol to HDL cholesterol ratio are often unchanged. For this and other reasons, a long term trial comparing thiazide type diuretics with drugs with the most favourable lipid-lipoprotein profile is needed. Until this is accomplished, in most settings diuretic-based regimens are still preferred initially since they are of proven, if limited, efficacy against the cardiovascular complications of hypertension. PMID- 2877849 TI - History of the development of sulphasalazine in rheumatology. PMID- 2877847 TI - Sulphasalazine: a review of 40 years' experience. AB - Sulphasalazine, devised by Dr Nana Svartz for the treatment of 'infective polyarthritis', has been used in the treatment of inflammatory bowel disease for more than 40 years. Many controlled trials have shown that sulphasalazine 4g daily will induce remissions in between one-half and three-quarters of patients with acute attacks of ulcerative colitis. When given in a dosage of 2g daily it will prevent relapses in quiescent colitis. Relapses are 5 times more likely in untreated patients. It is less effective in Crohn's disease, where it exerts only a transient benefit in patients with active colonic disease and fails to prevent relapse or recurrence. Sulphasalazine is absorbed from the small intestine, re excreted in bile and carried to the colon, where its azo bond is split by bacteria to release sulphapyridine, which is absorbed and is responsible for most of the drug's side effects, and 5-aminosalicylic acid, which is the active therapeutic moiety of the drug and exerts a beneficial topical action on the colonic mucosa. Side effects are common but are mainly reversible and not serious. Those related to high concentrations of sulphapyridine and to poor acetylation of the drug include gastrointestinal intolerance, malaise, headache, arthralgia, drug fever, effects on red blood cells and reversible male infertility. More serious, idiosyncratic side effects are skin rashes, leucopenia and agranulocytosis. Rarely, neurotoxicity, hepatotoxicity, polyarteritis, pulmonary fibrosis, a lupus-like syndrome and haemorrhagic colitis are produced. It is possible to desensitise most patients with drug-induced skin rashes. A number of less toxic alternatives to sulphasalazine have been devised and are undergoing trial. They either convey 5-aminosalicylic acid in a coated tablet to the colon or, when conjugated to a non-toxic carrier, release 5-aminosalicylic acid by bacterial cleavage there. Sulphasalazine remains a most useful drug in the treatment of inflammatory bowel disease after 40 years of use. PMID- 2877850 TI - Pharmacological and biochemical actions of sulphasalazine. AB - This review considers recent pharmacological and biochemical studies of sulphasalazine and its colonic metabolites, 5-aminosalicylic acid and sulphapyridine, in relation to the use of the parent drug for the treatment of ulcerative colitis and, more recently, rheumatoid arthritis. Several factors make it difficult to analyse the mode of action of sulphasalazine, such as the aetiology and variable course of the conditions it is used to treat, lack of suitable animal models, and the question of which moiety of the drug is active. An important feature of the pharmacokinetics of the drug after oral administration is the significance of the azo cleavage of sulphasalazine due to bacterial action. The effects of sulphasalazine on the metabolism of arachidonic acid to prostaglandins and leukotrienes have been widely studied because of the evidence that these substances are formed in increased amounts in inflammatory bowel diseases. The effects are complex, but it appears that sulphasalazine and 5 aminosalicylic acid are weak and very weak inhibitors, respectively, of both cyclo-oxygenase- and lipoxygenase-dependent pathways. The overall pharmacological profile may favour a more marked inhibition of the lipoxygenase pathway because of the additional ability of 5-aminosalicylic acid to enhance prostanoid production and of sulphasalazine to inhibit prostaglandin inactivation. Drugs with selective lipoxygenase inhibitory actions in the colon should thus be sought so as not to compromise the prostaglandin pathway. Other properties of sulphasalazine, including its immunosuppressive, antifolate, lymphocyte inhibitory and leucocyte modulatory actions, are also discussed in the context of the therapeutic uses of the drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877852 TI - Comparison of white blood cell dyscrasias during sulphasalazine therapy of rheumatoid arthritis and inflammatory bowel disease. AB - A total of 7 out of 158 rheumatoid arthritis patients followed for 6 months have developed leucopenia during sulphasalazine therapy at our centre. Two of these patients developed profound leucopenia which necessitated admission to a laminar flow unit, and case reports of these are documented in detail. These results are compared with those from other centres in the United Kingdom where patients with rheumatoid arthritis have been treated, and also with experience gained from patients with inflammatory bowel disease who have been treated with sulphasalazine. PMID- 2877851 TI - 5-Aminosalicylic acid or sulphapyridine. Which is the active moiety of sulphasalazine in rheumatoid arthritis? AB - Thirty patients with active rheumatoid arthritis participated in an open study of 6 months' treatment with either 5-aminosalicylic acid or sulphapyridine, the two moieties of sulphasalazine. Patients were assessed at regular intervals using a number of clinical and biochemical tests designed to detect specific antirheumatic activity. Patients taking sulphasalazine showed significant improvement in most parameters of disease activity, but those taking 5 aminosalicylic acid did not improve despite the fact that high serum concentrations of 5-aminosalicylic acid and acetyl 5-aminosalicylic acid were achieved. These results suggest that sulphapyridine is the active moiety of sulphasalazine. Its possible mode of action is discussed. Nausea was a frequent problem in patients taking sulphapyridine. Unless this problem can be overcome, sulphapyridine is unlikely to offer any therapeutic advantages over sulphasalazine in the treatment of rheumatoid arthritis. PMID- 2877853 TI - Side effect profile of 200 patients with inflammatory arthritides treated with sulphasalazine. AB - The side effect profile of sulphasalazine was documented in 200 patients with inflammatory joint disease treated with the drug for at least 1 year. Fifty-eight percent of patients developed one or more adverse reactions and in 21.5% the drug was withdrawn. A further 28% continued taking the drug at a reduced dose. Five percent of the side effects were judged to be potentially serious. In all patients the reactions subsided on either discontinuation of the drug or reduction of the dose. Gastrointestinal (33%) and central nervous system reactions (19%) were the most common, but all were relatively minor. Neutropenia (2%), thrombocytopenia (1%) and pan-hypogammaglobulinaemia (1%) were potentially the most serious effects. The side effect profile of sulphasalazine in inflammatory joint disease appeared to be similar to that in inflammatory bowel disease, but reactions were more frequent in inflammatory joint disease. Enteric coated sulphasalazine is a useful addition to the small number of slow acting antirheumatic drugs, and in view of its established efficacy, its level of toxicity was found to be 'acceptable' as long as patients were carefully monitored and regular blood tests were carried out. PMID- 2877854 TI - Variables affecting efficacy and toxicity of sulphasalazine in rheumatoid arthritis. A review. AB - Studies of sulphasalazine in rheumatoid arthritis have used largely empirical doses. The available literature suggests that the optimum dose appears to be greater than 40 mg/kg/day. Despite the relationship between dose and efficacy and a good correlation between dose and serum concentrations of sulphasalazine and its metabolites, no relationship has been demonstrated between efficacy and serum concentrations of sulphasalazine or its metabolites, although there is some suggestion that higher concentrations on single dosing are achieved in patients who develop upper gastrointestinal symptoms. Furthermore, acetylator phenotype does not affect efficacy, although upper gastrointestinal symptoms are more common in slow acetylators. PMID- 2877855 TI - Sulphasalazine for rheumatoid arthritis. Studies on dose, acetylator phenotype and efficacy. PMID- 2877856 TI - Assessing the progression of joint damage in rheumatoid arthritis. AB - Joint damage in rheumatoid arthritis can be assessed by plain radiographs of the hands and wrists. There are a number of established methods that give reproducible scores which relate to increasing joint damage by measuring erosions and loss of joint space. Only 3 placebo-controlled trials have shown convincing evidence that gold or cyclophosphamide reduce the rate of progression of joint damage. Most placebo-controlled studies have failed to show a beneficial effect of slow acting antirheumatic drugs on radiological joint damage progression. However, comparative studies or analyses of cohorts of patients taking slow acting antirheumatic drugs show comparable amounts of progression for patients receiving gold and other drugs in this category. In addition, patients who show a clinical response also have less radiological progression after 6 months' therapy. In these circumstances, sulphasalazine produces comparable rates of radiological progression to those produced by gold and penicillamine. There are many problems associated with the use of radiological assessments to determine the progression of rheumatoid arthritis; thus, this method should not be deemed the most important technique by which to measure the success of therapy. PMID- 2877857 TI - Long term outcome of treatment with sulphasalazine in rheumatoid arthritis. PMID- 2877858 TI - Sulphasalazine in the long term management of rheumatoid arthritis. AB - The clinical outcome of rheumatoid arthritis patients treated long term with sulphasalazine or parenteral gold was studied. The rate of withdrawal from gold because of inefficacy was less frequent than that for patients receiving sulphasalazine. However, patients on sulphasalazine withdrew less frequently because of adverse reactions. PMID- 2877859 TI - [Suppression of the ventilatory response to exercise during long-term treatment with beta-blockers]. PMID- 2877860 TI - Current issues in suicide prevention: reflections on the proceedings of the 13th International Congress for Suicide Prevention and Crisis Intervention. PMID- 2877861 TI - [Ultrastructural characteristics of the blood lymphocytes in some forms of sporadic T-cell lympholeukemia and leukemia associated with the HTLV virus]. AB - The electron microscopic study of the blood cells in some patients with sporadic T-cell acute lymphoblastic leukemias has shown some ultrastructural peculiarities similar to T-cell lympholeukemia associated with HTLV virus, that is important for the further elucidation of etiology and pathogenesis of the T-cell lymphoproliferative diseases. PMID- 2877862 TI - Opioids act centrally to modulate stress-induced decrease in luteinizing hormone in the rat. AB - Because endogenous opioid peptides (EOP) and CRF are activated during stress and decrease LH levels when injected centrally, we have explored the roles of these peptides in the stress-induced inhibition of LH secretion. Three opioid peptide systems [i.e. endorphin (END), enkephalin, dynorphin (DYN)], are present in the hypothalamus, acting on different opiate receptor subtypes (i.e. mu, delta, kappa). We first evaluated which EOP might be involved in the stress-induced decrease of LH levels. Immunoneutralization of EOP and pharmacological blockade of opiate receptors were used to reverse the decrease in LH induced by inescapable intermittent footshock in castrated male rats. Anti-beta-END and anti DYN-A serum (intracerebroventricularly [icv]) or pretreatment with beta-END antagonist, beta-human END-(6-31) (2 and 5 nmol, icv), or with kappa-antagonists, Mr1452 MS and Mr2266 BS (10 mg/kg BW, ip), reversed electroshock-induced decrease in LH concentrations. beta-funaltrexamine (beta-FNA), an irreversible mu 1-opiate receptor antagonist, was partially effective in blocking the inhibitory effect of stress on LH levels. Neither passive immunization with anti-enkephalin nor the pretreatment with the delta-opiate receptor antagonist, ICI 154,129, (10 and 100 nmol, icv) modified the effect of stress. We then evaluated which endogenous opioid ligands and/or receptors might mediate the inhibitory effect on LH levels of 2 nmol ovine CRF injected icv. Anti-beta-END serum and beta-human END-(6-31), reversed the CRF-induced decrease of LH concentrations, whereas beta-FNA was only partially active. Anti-DYN-A and anti-ENK serum, kappa- and delta-antagonists did not prevent the decline of LH levels in rats receiving CRF centrally. These data suggest that stress-induced inhibition of LH secretion involves the stimulation of beta-END and DYN-A systems via mu/epsilon- or kappa-opiate receptors and that the decrease in circulating LH levels induced by centrally administered CRF may be mediated by the activation of beta-END system. Therefore, it is possible that the activation of the central CRF/beta-END pathway may play an important role in the stress-induced inhibition of reproductive functions. PMID- 2877863 TI - Dibutyryl adenosine cyclic monophosphate regulates differentiation of type A spermatogonia with vitamin A in adult mouse cryptorchid testis in vitro. AB - Surgically prepared cryptorchid mouse testes containing only type A spermatogonia were cultured with (Bu)2cAMP in combination with vitamin A (retinol). Treatment with (Bu)2cAMP and retinol for 12-24 h and with basal medium for an additional 8 days stimulated mitotic activity in type A spermatogonia and induced differentiation of germ cells. However, (Bu)2cAMP alone did not induce differentiation of type A spermatogonia. Moreover, when cryptorchid testes were treated with (Bu)2cAMP for longer than 3 days in the presence or absence of retinol, differentiation of type A spermatogonia did not take place; disintegration of the seminiferous tubules occurred instead. When the cryptorchid testes were cultured for 24 h in a medium containing a fixed concentration of retinol and varying concentrations of (Bu)2cAMP from 0.001-0.4 mM, there was a dose-dependent increase in the number of differentiated and mitotic germ cells and type A spermatogonia. Likewise, at a fixed dose of (Bu)2cAMP and increasing concentrations of retinol, a dose-dependent increase in the number of differentiated and mitotic germ cells occurred. However, the number of type A spermatogonia was decreased. The addition of puromycin, cycloheximide, and actinomycin D to the medium completely blocked retinol-(Bu)2cAMP-induced differentiation of the germ cells. The present results suggest that cAMP and retinol trigger biochemical events promoting the synthesis of specific macromolecules involved in the proliferation and differentiation of type A spermatogonia. PMID- 2877864 TI - Involvement of hypothalamic growth hormone (GH)-releasing factor in GH secretion induced by intracerebroventricular injection of somatostatin in rats. AB - Intracerebroventricular (icv) injection of somatostatin-14 (SRIF-14, 5 micrograms/rat) caused an increase in plasma GH in urethane-anesthetized rats and in conscious freely moving rats. Antiserum specific for rat GH-releasing factor (GRF) (0.5 ml/rat, iv) blunted GH release induced by SRIF-14 in these animals. The antiserum also suppressed spontaneous GH surges in conscious rats. In contrast, GH release induced by prostaglandin E2 (5 micrograms/100 g BW, iv) was not affected by the antiserum. SRIF-14 (5 micrograms/rat, icv) also raised plasma GH levels in conscious rats during the constant iv infusion of SRIF-14 (55 ng/55 microliter X min) which suppressed spontaneous GH secretion. Neither plasma TSH levels nor TSH release induced by a TRH analog were affected by icv injection of SRIF-14. These results suggest that the central stimulating effect of SRIF-14 on rat GH secretion is mediated, at least in part, by hypothalamic GRF and not due to a direct action on the pituitary. PMID- 2877865 TI - Evidence that growth hormone-releasing factor stimulates somatostatin release in vitro via beta-endorphin. AB - Previous results indicate that GH-releasing factor (GRF) induces a dose-related stimulation of somatostatin (SRIF) release from median eminence fragments incubated in vitro. In the present investigation we examined whether this action was mediated by other neurotransmitters or neuromodulators. Studies using receptor blockers for dopamine (pimozide), alpha-adrenergic receptors (phentolamine), and muscarinic cholinergic receptors (atropine) revealed that these receptor blockers, at a dose of 10(-6) M, which was capable of blocking the response to the relevant transmitter in previous studies, had no effect on basal release of SRIF in the static incubation system and failed to modify the response to GRF (10(-10) M). On the other hand, the opiate receptor blocker naloxone at a dose of 10(-6) M, although failing to alter basal release, completely blocked the response to 10(-10) M GRF. To determine the opioid peptide involved in mediating the SRIF release induced by GRF, highly specific antibodies directed against beta endorphin were added to the in vitro incubation system. These antibodies significantly depressed basal release SRIF and completely blocked the response to 10(-10) M GRF. Incubations in the presence of normal rabbit serum or highly specific antiserum directed against alpha MSH had no effect on either basal release of SRIF or that induced by GRF. These results suggest that in this incubation system there is a beta-endorphin tone which is partially responsible for the basal release of SRIF and that the stimulation of SRIF release induced by GRF is mediated via beta-endorphin terminals, which presumably synapse on the terminals of the somatostatinergic neurons in the median eminence fragment. PMID- 2877866 TI - Mediation of insulin-like growth factor actions by the insulin receptor in H-35 rat hepatoma cells. AB - We have used H-35 rat hepatoma cells to test whether the type II insulin-like growth factor (IGF) receptor mediates metabolic responses to IGF-II. On the basis of both affinity cross-linking experiments and competition binding experiments, H 35 cells display insulin and type II IGF receptors, but not type I IGF receptors. IGF-II and multiplication-stimulating activity (MSA; the rat homolog of IGF-II) stimulate tyrosine aminotransferase, amino acid transport, and glycogen synthase activities to the same magnitude as insulin. However, MSA and IGF-II stimulate these metabolic responses only at high concentrations, indicating that these peptides are acting through the insulin receptor. Incubation of H-35 cells with MSA also induces a state of unresponsiveness to the further actions of both MSA and insulin. There is no associated loss of either insulin or IGF-II binding, indicating that desensitization occurs at a postbinding step in hormone action. The high concentration of MSA necessary to induce desensitization is also consistent with MSA acting through the insulin receptor. We conclude that in H-35 cells, the insulin receptor, rather than the type II IGF receptor, mediates the metabolic responses stimulated by MSA and IGF-II as well as the MSA-induced desensitization to insulin and MSA action. PMID- 2877867 TI - Indices of noradrenergic function in the central nervous system of seizure-naive genetically epilepsy-prone rats. AB - Norepinephrine concentrations and tyrosine hydroxylase activity were determined in the brains of moderate-seizure and severe-seizure genetically epilepsy-prone rats (GEPRs) and in nonepileptic control rats. Both moderate-seizure (GEPR-3) and severe-seizure (GEPR-9) animals had widespread abnormalities in brain norepinephrine concentrations. Abnormalities in tyrosine hydroxylase activity were restricted to the midbrain. The state of abnormal seizure susceptibility, but not severity, in the GEPR may be determined by noradrenergic deficits in the hypothalamus/thalamus. Both seizure severity and susceptibility may be determined by noradrenergic deficits in the telencephalon, midbrain, and pons-medulla. Seizure severity but not susceptibility may be determined by noradrenergic abnormalities in the cerebellum. PMID- 2877868 TI - Dicarboxylic amino acids block epileptiform activity in hippocampal slice. AB - Effects of prolonged (5-10 min) continuous perfusion of excitatory amino acids on penicillin (PEN)-evoked epileptiform activity in hippocampal slices were examined with extracellular and intracellular recordings. L-glutamate (GLU), L-aspartate (ASP), quisqualate (QUIS), and N-methyl-D,L-aspartate reversibly depressed multiple (epileptiform) population spikes elicited by PEN (1.7 mM). Intracellularly recorded, PEN-evoked paroxysmal depolarization shifts (PDS) were partially blocked by 1 mM GLU and largely eliminated by 2 mM GLU or ASP. In the presence of PEN, perfusion with both GLU and ASP induced a transient 4 to 6-mV depolarization, usually followed by spontaneous return of membrane potential to control levels. During the amino acid (AA)-induced block of epileptiform activity, there was no significant change in resting membrane potential, input resistance, or the ability to fire action potentials in response to depolarization, indicating that the decreased responsiveness is not a consequence of nonspecific pyramidal cell overdepolarization. The observed depression of epileptiform activity by continued exposure to GLU and its analogues may reflect desensitization or another regulatory mechanism to limit overexcitation. PMID- 2877869 TI - Activities of gamma-glutamyl transferase, 5'-nucleotidase and alkaline phosphatase in human duodenal aspirate. AB - Duodenal aspirates were obtained before, during, and after stimulation with secretin-cholecystokinin in 26 patients whose pancreatic function was classified as normal, moderately reduced, or severely reduced. The activities of gamma glutamyltransferase (GGT), alkaline phosphatase (ALP), and 5'-nucleotidase (5NT) in the aggregated duodenal aspirate collected 10-40 min after stimulation showed marked overlap between the functional groups and lacked diagnostic value. For all three enzymes, the peak response occurred later in the severely impaired group than in those with normal pancreatic function. The three enzymes showed significant positive correlations with each other, and were negatively correlated with the output of trypsin and chymotrypsin and, in contrast with these proteolytic enzymes which were reduced in pancreatic disease, GGT, ALP, and 5NT all tended to increase with pancreatic disease. Contrary to a previous report, GGT did not serve as a useful index of pancreatic cancer in this study. PMID- 2877870 TI - Purification and characterization of human placental microsomal aminopeptidase: immunological difference between placental microsomal aminopeptidase and pregnancy serum cystyl-aminopeptidase. AB - Human placental microsomal aminopeptidase (microsomal PAP) was purified 3,880 fold from human placenta and characterized. The enzyme was solubilized from membrane fractions with Triton X-100 and also trypsin digestion, and subjected to zinc sulfate fractionation, chromatographies with DE-52, hydroxylapatite, Sephacryl S-300 and lentil lectin-Sepharose 4B, and finally affinity chromatography with bestatin-Sepharose 4B. Microsomal PAP was separated from aminopeptidase A (AAP) by affinity chromatography. The apparent relative molecular mass (Mr) of the enzyme was estimated to be 220,000 by high-performance liquid chromatography with an aqueous gel column. The purified enzyme gave almost a single band with a molecular mass of 140,000 by sodium dodecyl sulfate (SDS) gel electrophoresis. The isoelectric point of the enzyme was 5.2. The purified enzyme was most active at pH 8.0 with L-leucine-p-nitroanilide as substrate; the Km value for this substrate was 1.1 mmol/l. The microsomal PAP was immunologically different from the pregnancy serum cystyl aminopeptidase (serum PAP). PMID- 2877871 TI - Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. AB - To identify structural characteristics of the closely related cell surface receptors for insulin and IGF-I that define their distinct physiological roles, we determined the complete primary structure of the human IGF-I receptor from cloned cDNA. The deduced sequence predicts a 1367 amino acid receptor precursor, including a 30-residue signal peptide, which is removed during translocation of the nascent polypeptide chain. The 1337 residue, unmodified proreceptor polypeptide has a predicted Mr of 151,869, which compares with the 180,000 Mr IGF I receptor precursor. In analogy with the 152,784 Mr insulin receptor precursor, cleavage of the Arg-Lys-Arg-Arg sequence at position 707 of the IGF-I receptor precursor will generate alpha (80,423 Mr) and beta (70,866 Mr) subunits, which compare with approximately 135,000 Mr (alpha) and 90,000 Mr (beta) fully glycosylated subunits. PMID- 2877872 TI - Location of the 100 kd-50 kd accessory proteins in clathrin coats. AB - We present a three-dimensional map of the clathrin coat of coated vesicles, generated from tilt series of electron micrographs of unstained specimens embedded in vitreous ice. We have examined native placental coated vesicles and coats reassembled from their purified constituents, namely clathrin triskelions and accessory proteins of approximate mol. wts 100 kd and 50 kd. Our results show that the accessory proteins contribute a further shell of density within the double shell of the clathrin cage, extending from the terminal domains of the clathrin to the membrane of the vesicle. The thickness of the complete coat is approximately 22 nm. PMID- 2877873 TI - Sequential expression of murine homeo box genes during F9 EC cell differentiation. AB - We have isolated and characterized a previously unknown member of the murine homeo box family. The new locus, m31, is located on chromosome 15 and is more homologous to sequences contained in the Drosophila homeotic gene, Antp, than to any other known murine homeo box. We show that this gene encodes a 2.7 kb mRNA which is expressed during mouse embryogenesis and during differentiation of F9 teratocarcinoma cells into parietal endoderm cells. The transcript appears late in this differentiation process and is most abundant at a time when the F9 cells begin to express tissue-specific markers and the expression of another murine homeo box gene, m6, has decreased. PMID- 2877876 TI - Pharmacology of vecuronium in patients with end-stage renal failure. AB - Vecuronium was administered as an intravenous bolus (50 micrograms kg-1) to 10 normal and 10 anephric patients. The elimination half-life was 50.7 +/- 20.3 min in normal patients and 67.826.3 min in anephric patients. The plasma clearance was 3.6 +/- 1.5 ml min-1 for normal patients and 4.5 +/- 2.6 ml min-1 kg-1 for anephric patients. Only the volume of the second compartment was statistically increased (+90%, P less than 0.05) in anephric patients. The duration of action in normal patients (25.3 +/- 9.8 min) was comparable to the duration of action in patients with renal failure (32.8 +/- 10.7 min), but the recovery index was prolonged (+45%, P less than 0.05) in anephric patients. PMID- 2877874 TI - Comparison of factor IX methylation on human active and inactive X chromosomes: implications for X inactivation and transcription of tissue-specific genes. AB - Maintenance of dosage compensation for housekeeping genes on the human X chromosome is mediated through differential methylation of clustered CpG nucleotides associated with these genes. To determine if methylation has a role in maintaining inactivity of X-linked genes which show tissue-specific expression, we examined the locus for blood clotting Factor IX. The analysis encompassed 91% of the HpaII and HhaI sites in the 41-kb region that includes the presumed promoter region, 5 kb of 5'- and 4 kb of 3'-flanking sequences. Although there are sex differences in methylation of the locus in leukocytes, the methylation pattern in liver, where the gene is expressed, is essentially the same for loci on the active and inactive X chromosome. The lack of differences in methylation of active and inactive genes makes it unlikely that methylation within the locus has a role in expression of the Factor IX gene. These findings, along with the absence of clustered CpG dinucleotides within the Factor IX locus, suggest that functional differences in DNA methylation related to X chromosome dosage compensation may be limited to CpG clusters. In any event, dosage compensation seems to be maintained regionally, rather than locus by locus. PMID- 2877875 TI - The effect of ketamine on the peripheral circulation: a possible sympathetic ganglion blocking effect. AB - The effects of induction of anaesthesia, endotracheal intubation and surgical stimuli on the systemic and peripheral circulations were studied in three groups of patients. In group KA (n = 8) anaesthesia was induced with ketamine (2 mg kg 1) and alcuronium, supplemented by N2O-O2 alone; in group KAH (n = 9) 0.5% halothane was added to the N2O-O2; and in the control group TAH (n = 8) anaesthesia was induced with a sleep dose of thiopentone and alcuronium, supplemented by N2O-O2 and halothane. The circulation in the finger was monitored by photo-electric plethysmography. Induction produced a significant pressor response in both ketamine groups, but not in the TAH group, while the finger plethysmogram demonstrated peripheral vasodilatation in all three groups. Intubation, on the other hand, elicited a significant pressor response in the TAH and in the KAH group but not in the KA group. The finger plethysmogram, however, always showed peripheral vasoconstriction during intubation in the thiopentone group (TAH) but never in either of the ketamine groups. The results suggest that ketamine exerts a peripheral ganglion blocking effect. PMID- 2877877 TI - Impaired production of alpha and gamma interferon in asymptomatic homosexual males. AB - In vitro production of alpha interferon and gamma interferon was examined in cell cultures from 90 asymptomatic homosexual males and 19 healthy heterosexual male controls. The production of alpha and gamma interferon was significantly suppressed in homosexuals as compared to that in heterosexual controls (p less than 0.005 and p less than 0.001, respectively). Forty-one of the homosexuals produced less gamma interferon than any of the heterosexual controls. Antibodies against the human immune system virus (HIV) were found in eight homosexuals, who produced significantly less alpha and gamma interferon than did the HIV seronegative homosexuals (p less than 0.02). Neither carriage of Entamoeba histolytica or Giardia lamblia nor serological evidence of infection with cytomegalovirus, Epstein-Barr virus or hepatitis B virus was associated with a significantly lower production of interferon than that found in homosexual males seronegative for these infections. No correlation was found between number of partners or practice of passive anal intercourse and production of interferons in homosexual men. It is concluded that the significantly lower production of both alpha and gamma interferon in asymptomatic homosexual males may play an important role in susceptibility to viruses, including HIV. PMID- 2877879 TI - Reconstitution of CF1-depleted thylakoid membranes with complete and fragmented chloroplast ATPase. The role of the delta subunit for proton conduction through CF0. AB - Chloroplast ATPase (CF1) was isolated from spinach, pea and maize thylakoids by EDTA extraction followed by anion-exchange chromatography. CF1 was purified and resolved by HPLC into integral CF1, and CF1 lacking the delta & epsilon subunits: CF1(-delta) and CF1(-epsilon). Washing Mono-Q-bound CF1 with alcohol-containing buffers followed by elution without alcohol produced the beta subunit and in separate peaks CF1(-delta) and CF1(-epsilon). Elution from Mono Q in the presence of tenside yielded a beta delta fragment, CF1(-delta) and CF1(-delta epsilon). Chloroplasts were CF1-depleted by EDTA extraction. Reconstitution of photophosphorylation in these 'EDTA vesicles' was obtained by addition of CF1 and its fragments. CF1, CF1(-delta) and CF1(-delta epsilon) were active with cross reactivity between spinach, pea and maize. delta-containing CF1 always reconstituted higher activities than delta-deficient CF1. The beta delta fragment and dicyclohexylcarbodiimide (DCCD)-inhibited CF1 also were reconstitutively active while beta and DCCD-inhibited CF1(-delta) were not. These results support the notion that subunit delta can function as a stopcock to the CF0 proton channel as proposed by Junge, W., Hong, Y. Q., Qian, L. P. and Viale, A. [(1984) Proc. Natl Acad. Sci. USA 81, 3078-3082]. PMID- 2877878 TI - Chlamydial respiratory infection in childhood and spurious immunoglobulin M. AB - The role of Chlamydia trachomatis was investigated in lower respiratory tract infections in 254 children. The organism was not isolated in any child but Bordetella pertussis was isolated from 65. Two of the latter and one of the remaining 189 children with negative isolation, however, had immunoglobulin M (IgM) antibodies to Chlamydia trachomatis (titers of 1:64, 1:64 and 1:128). Exhaustive absorption of the sera with bordetella antigen left the chlamydial titers unchanged, thus excluding the possibility of cross-reactivity with bordetella antigen. To determine whether nonspecific stimulation of B lymphocytes played a role, sera from 72 children with infectious mononucleosis were examined. Chlamydial IgM antibodies (greater than or equal to 1:64) were detected in 14 of these sera, significantly more often than in other acute childhood infections (p = 0.002). Serotyping showed that these antibodies had a heterogeneous specificity in different sera and a reactivity pattern suggesting they were monoclonal. The association found between chlamydial IgM antibodies and Epstein-Barr virus infection implies that there is nonspecific production of these antibodies in infectious mononucleosis, suggesting that similar nonspecific antibody production could occur in other infections. This might explain the chlamydial IgM found in children with lower respiratory tract infections in whom chlamydial infection could not be confirmed by isolation. PMID- 2877880 TI - Accessibility of F0 subunits from Escherichia coli ATP synthase. A study with subunit specific antisera. AB - Antisera have been raised against denatured and non-denatured subunits a, b and c of the F0 complex of the ATP synthase from Escherichia coli. The subunit specificity of the antibodies has been established with immunoblot analysis or enzyme-linked immunosorbent assay (ELISA). In inside-out oriented membrane vesicles the binding avidities of both sets of antisera, against denatured and non-denatured subunits of F0, were similar in the presence as well as in the absence of the F1 part. F1-depleted everted membrane vesicles always produced an efficient binding of the different antisera. In the presence of F1 no antibody recognition could be observed with the anti-a antisera, while anti-b and anti-c antisera showed strong binding. However, a higher membrane protein concentration was necessary for the same antibody binding as in F1-stripped vesicles. In membrane vesicles with right-side-out orientation the recognition of the three F0 subunits was dependent on the antisera set used. Antisera raised against denatured subunits showed no binding to the membrane vesicles, only in case of anti-(dodecylsulfate-denatured b) antiserum could a slight affinity be detected. An antigen-antibody recognition with all three F0 subunits occurred when the antisera against non-denatured subunits were incubated with membrane vesicles of right-side-out orientation. The membrane protein concentration which was necessary to produce a significant binding was 10-100-fold higher compared to that of F1-depleted everted membrane vesicles. PMID- 2877881 TI - Column centrifugation generates an intersubunit disulfide bridge in Escherichia coli F1-ATPase. AB - Passage of F1-ATPase through a centrifuge column [Penefsky, H. S. (1979) Methods Enzymol. 56, 527-530] caused formation of a product with a relative molecular mass of 72,000 as determined by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The product was identified as cross-linked alpha and delta subunits by using Western blots and subunit-specific monoclonal antibodies. The cross-link was reversed by 50 mM dithiothreitol implying that it was a disulfide bridge. Formation of the cross-link was inhibited by 2 mM EDTA and was stimulated in some buffers by the addition of 10 microM CuCl2. Time course experiments indicated that the majority of the cross-link formed while the enzyme was passing through the column. Thus the cross-link induced by column centrifugation arose from the rapid, heavy-metal-ion-catalysed oxidation of two sulfhydryl groups, one on the alpha subunit and one on the delta subunit, to a disulfide. These results demonstrate that care must be exercised when running proteins through centrifuge columns as potentially deleterious disulfide formation can result. An anti-beta monoclonal antibody was capable of immunoprecipitating the entire enzyme including the cross-linked subunits, implying that the cross-linked alpha and delta subunits were still a part of F1. The formation of the cross-link affected neither the hydrolytic activity of the enzyme nor its susceptibility to inhibition by epsilon subunit. The cross-linked enzyme was unable to bind to F1 depleted membranes in experiments in which soluble F1 and membranes were separated by centrifugation. Column centrifugation did not generate the cross link on membrane-bound enzyme. These results indicate that the alpha-delta cross link results in a loss of binding affinity between F1 and F0. PMID- 2877882 TI - Acute changes in renal function induced by bisoprolol, a new cardioselective beta blocking agent. AB - The acute effects of bisoprolol 10 mg i.v., a new beta1-selective adrenoceptor antagonist, on heart rate, mean blood pressure (mBP), glomerular filtration rate (GFR), para-aminohippuric acid clearance (CPAH), sodium clearance, urine volume and plasma renin activity (PRA), were studied in 6 patients with essential hypertension. Heart rate decreased by 23%, mBP remained unchanged, and GFR decreased by 14% and CPAH by 23%. PRA was depressed on average by 25%. Urine volume and sodium clearance also declined by 9 and 13%, respectively, but the changes were not statistically significant. The fall in heart rate was significantly correlated with that in GFR and CPAH. Changes in GFR were correlated significantly with those in CPAH. The acute changes in renal function induced by bisoprolol are considered to be due to a reduction in cardiac output and increased systemic vascular resistance. PMID- 2877883 TI - Pharmacokinetics of single and multiple doses of flusoxolol (Ro 31-1411) in healthy subjects. AB - Flusoxolol (Ro 31-1411) is the pharmacologically active optical isomer of Ro 31 1118, a potent cardioselective beta-adrenoceptor antagonist with partial agonist activity. It was given to 6 healthy volunteers in a single dose, 40 mg, and then in multiple doses, 40 mg daily for 8 days. Plasma concentration data were best described by a linear two-compartment pharmacokinetic model with first order absorption, and the results confirmed linear kinetics. Pharmacokinetic data for flusoxolol were comparable to those for the racemate Ro 31-1118. PMID- 2877884 TI - 5-Aminosalicylic acid in patients with an ileo-rectal anastomosis. A comparison of the fate of sulfasalazine and Pentasa. AB - The pharmacokinetics of 5-aminosalicylic acid (5-ASA) from sulphasalazine (SASP) and the slow-release 5-ASA preparation Pentasa was investigated in a cross-over study in 9 otherwise healthy patients with an ileo-rectal anastomosis. The 24 hour recoveries of the drugs were 90.5% and 84.7%, respectively. The median release of 5-ASA from SASP was 50% and from Pentasa 75%. Equal amounts of 5-ASA (18.0% vs 17.9%) were found in the faeces, and a significantly larger amount (4.4% vs 28.9%) of the metabolite N-acetyl-5-aminosalicylic acid (ac-5-ASA) was found in faeces following Pentasa. A larger amount of 5-ASA was absorbed and subsequently excreted in the urine, mainly as the metabolite (2.5% vs 20.5%) from Pentasa. This confirms previous results in ileostomized patients treated with Pentasa. The present findings also demonstrate that bacterial azo-reduction of SASP in patients with ileorectal anastomosis may be an adequate way to deliver 5 ASA in this type of patient. Both treatments may be used in these patients during a flare up of ulcerative colitis, but randomized studies are needed. PMID- 2877885 TI - Interaction of bisoprolol with cimetidine and rifampicin. AB - In 6 healthy volunteers the pharmacokinetics of bisoprolol under steady-state conditions was investigated over three consecutive phases: over 7 days of 10 mg of bisoprolol once daily per os, 7 days of 10 mg of bisoprolol once daily plus 400 mg of cimetidine t.i.d. and 14 days of 10 mg of bisoprolol and 600 mg of rifampicin once daily with adequate intervals free of medication. After therapy with bisoprolol alone peak plasma levels (Cssmax) of the beta-blocker were 55.5 +/- 6.4 ng/ml (means +/- SEM), area under the plasma level-time curve (AUC tau) was 597 +/- 70 ng/ml.h, total body clearance (CL) 15.8 +/- 1.8 l/h and elimination half-lives (t1/2 beta) 10.1 +/- 1.2 h. Cimetidine did not cause any significant changes in the pharmacokinetics of bisoprolol. Co-administration of rifampicin resulted in a decrease in Cssmax (43.0 +/- 6.9 ng/ml), AUC tau (397 +/ 54 ng/ml X h) and t1/2 beta (6.2 +/- 0.4 h). Accordingly, total body clearance increased to 23.8 +/- 2.5 l/h (p less than 0.05). In conclusion bisoprolol showed a statistically significant but probably clinically not important interaction with the enzyme-inducing drug rifampicin, but not with the enzyme inhibitor cimetidine. PMID- 2877886 TI - Two natural killer cell populations which belong to T cell lineage in nude mice. AB - Enriched natural killer (NK) cell populations from BALB/c nude mice obtained by using nylon wool column (NWC) separation were stained with anti-Thy-1 and anti asialo GM1 (GA1), and then were fractioned by flow cytometry into 4 cell populations: Thy-1+GA1+ cells, Thy-1+GA1- cells, Thy-1-GA1+ cells and Thy-1-GA1- cells. These cell populations were sorted out by flow cytometry and were examined for NK activity. Of the sorted cells, high NK activity was found in the two populations, Thy-1+GA1+ cells and Thy-1-GA1+ cells. In the other populations expressing Thy-1 antigen alone or expressing neither GM1 nor Thy-1, NK activity was almost undetectable. The two cell populations with NK activity were lineaged with respect to rearrangement of the T cell receptor genes. Southern gel analysis using a cDNA probe containing the D beta 1, J beta 1.3 and C beta 1 genes of the T cell receptor showed a reduction of the germ-line band of DNA in the 3 fractionated populations other than Thy-1-GA1- cells. Since these observations were demonstrated in nude spleen cells, it is indicated that the cells with NK activity belong to T cell lineage even if they lack Thy-1 expression and that they may develop out of the thymus, if they express Thy-1 antigen. PMID- 2877887 TI - Characterization of alpha 1-adrenoceptors which increase cyclic AMP accumulation in rat cerebral cortex. AB - The pharmacological properties of the alpha-adrenoceptors which increase cyclic AMP accumulation were studied in slices of rat cerebral cortex after inactivation of beta-adrenoceptors with bromoacetylalprenololmenthane. Norepinephrine increased basal cyclic AMP accumulation 2-fold, and potentiated the effect of adenosine 5-fold. The Ki and EC50 values for antagonists and agonists for both the basal and potentiated responses were generally similar to those for alpha 1 adrenoceptor-stimulated inositol phosphate accumulation in the same preparation. However, significant differences in the potencies of all agonists, and the antagonists phentolamine and BE2254 were observed between the basal and potentiated cyclic AMP responses. The differences in agonist potencies did not appear to be due to the existence of a receptor reserve. Norepinephrine, epinephrine, alpha-methylnorepinephrine and 6-fluoronorepinephrine were full agonists, while methoxamine and phenylephrine were partial agonists in both systems. The results suggest that norepinephrine increases cyclic AMP accumulation in rat cerebral cortex through alpha 1-adrenoceptors similar to those increasing phosphatidylinositol metabolism in the same tissue. PMID- 2877888 TI - 3-(Methoxycarbonyl)-amino-beta-carboline, a selective antagonist of the sedative effects of benzodiazepines. AB - We have previously described the synthesis of a novel compound, 3 (methoxycarbonyl)-amino-beta-carboline (beta-CMC), which has a high in vitro affinity for the benzodiazepine receptor. In vivo testing showed that this compound had a restricted pharmacological profile. beta-CMC lacked intrinsic activity but it antagonized the convulsions induced by the methyl ester of beta carboline-3-carboxylic acid, an inverse agonist of the benzodiazepine receptor. Moreover, beta-CMC selectively antagonized the sedative but not the anxiolytic or anticonvulsant effects of benzodiazepines. The possible mechanisms involved in the selective antagonism of the sedative effects of benzodiazepines by beta-CMC are discussed. PMID- 2877890 TI - Ifoxetine, a compound with atypical effects on serotonin uptake. AB - Ifoxetine (CGP 15210 G; (+/-)-bis-[cis-3-hydroxy-4-(2,3-dimethyl-phenoxy)] piperidine sulfate) prevented the depletion of serotonin (5-HT) induced by H 75/12 and p-chloromethamphetamine in the rat brain, and that caused by endogenously released dopamine after the combined administration of haloperidol and amfonelic acid in the rat striatum. These effects are typically caused by compounds that inhibit 5-HT reuptake. Unexpectedly, ifoxetine only weakly inhibited the uptake of radiolabelled 5-HT into rat brain synaptosomes in vitro or ex vivo, the human thrombocytes in vitro or into rat thrombocytes after pretreatment. The following, among the possible explanations for this apparent discrepancy, were considered and regarded as unlikely: the involvement of an active metabolite; the possibility that ifoxetine accumulates in the brain to an extent sufficient to cause in vivo uptake inhibition; a pharmacokinetic interaction with the depleting agents. The possibility that the depletor tests give false positives was also considered. However, ifoxetine lowered brain 5 hydroxyindoleacetic acid and reduced the accumulation of 5-hydroxytryptophan after central decarboxylase inhibition. This suggests that it also interferes with 5-HT metabolism in the absence of depleting agents, which means that it interacts in some way with serotonergic transmission. Ifoxetine displayed weak or no interactions with 5-HT1, 5-HT2, alpha 1-, alpha 2- and beta-noradrenoceptors, histamine H1, muscarinic acetylcholine, opiate, GABA A, and benzodiazepine receptors in vitro, and with dopamine and 5-HT2 receptors in vivo. It did not antagonize the noradrenaline (NA) depletion induced by H 77/77 in rat brain and only weakly interfered with the uptake of i.v. injected radiolabelled NA into the rat heart. This suggests that its interaction with the 5-HT system is specific. Due to its atypical properties, among which the rather weak potentiation of the neurological effects of 5-hydroxytryptophan is also important, ifoxetine may exhibit a therapeutic and/or side-effect profile which differs from that of classical 5-HT uptake inhibitors. PMID- 2877891 TI - Relaxation of isolated mesenteric arteries by des-Arg9-bradykinin stimulation of B1 receptors. AB - The present studies were conducted to determine whether des-Arg-kinins can produce relaxation of isolated vessels. Both des-Arg9-bradykinin and bradykinin produced dose-dependent relaxations of isolated rabbit superior mesenteric arteries. Des-Arg9-bradykinin (ED50 = 7.2 X 10(-9) M) was 8.5 times more potent than bradykinin (ED50 = 6.1 X 10(-8) M). Des-Arg9-bradykinin-mediated relaxation was inhibited by the specific B1 receptor antagonist [Leu8]des-Arg9-bradykinin which produced parallel shifts in the dose-response curve. Schild regression analysis of the data established a pA2 value (6.46) similar to that reported for B1 receptor-mediated contraction. Although the relaxant effect of bradykinin was also inhibited by the B1 antagonist, parallel shifts in the dose response curve were not produced. Relaxation of the mesenteric artery by both des-Arg9 bradykinin and bradykinin was inhibited by the cyclooxygenase inhibitor indomethacin. The results of these studies indicate that in addition to vasoconstriction, des-Arg9-bradykinin can produce vasorelaxation which may be mediated through stimulation of B1 kinin receptors and the subsequent release of prostaglandins. PMID- 2877892 TI - CGP 20712 A: a useful tool for quantitating beta 1- and beta 2-adrenoceptors. AB - CGP 20712 A (1-[2-((3-carbamoyl-4-hydroxy)phenoxy)ethylamino]-3- [4-(1-methyl-4 trifluoromethyl-2-imidazolyl) phenoxy]-2-propanol methanesulfonate), a specific beta 1-adrenoceptor antagonist, was tested for resolution of beta 1- and beta 2 adrenoceptors in an in vitro [3H]dihydroalprenolol ([3H]DHA) binding assay. Competition experiments, using rat neocortical and cerebellar membranes, yielded two dissimilar concentration-effect curves. A distinct biphasic curve was evident for neocortex, with a plateau at 100 nM CGP 20712 A (60% [3H]DHA displacement). This plateau indicated a differentiation between beta 1- and beta 2 adrenoceptors; the ratio of IC50-beta 2 to IC50-beta 1 was approximately 10,000. In contrast, only a monophasic curve was obtained for cerebellum. CGP 20712 A is a useful tool for estimating percentages of beta 1- and beta 2-adrenoceptors in a given tissue. PMID- 2877889 TI - Opposing effects of D-1 and D-2 receptor antagonists on acetylcholine levels in the rat striatum. AB - In contrast to D-2 or mixed D-1/D-2 receptor antagonists which decrease rat striatal acetylcholine levels, the D-1 receptor antagonist SCH 23390 increased this biochemical parameter (ED50 = 0.04 mg/kg s.c.) suggesting a reduction of acetylcholine turnover. SCH 23390 blocked the ability of haloperidol or sulpiride to diminish striatal acetylcholine levels and potentiated the increase in this biochemical parameter induced by the selective D-2 receptor agonist LY 141865. These findings indicate that blockade of D-1 and D-2 receptors causes opposite actions on striatal cholinergic neurons. PMID- 2877893 TI - Beta 2-adrenoceptor selectivity in four series of beta-adrenoceptor agonists. AB - We studied the effect of two catechol and two resorcinol series of beta adrenoceptor agonists on isolated papillary (beta 1-adrenoceptors) and soleus (beta 2-adrenoceptors) muscles preparations from the guinea-pig. One of the catechol and one of the resorcinol series were substituted by branched alkyl groups on the amino nitrogen, and the other two series were substituted by cycloalkyl groups. It was found that: the catechol derivatives were more potent than their corresponding resorcinol derivatives on both the papillary and the soleus muscle preparations, the resorcinol derivatives were more selective for the soleus muscle than their corresponding catechol derivatives, the substitution on the amino nitrogen gave compounds that were highly selective for the soleus muscle, both in the catechol and the resorcinol series. Greatest selectivity was obtained with a tertiary butyl group. the branched alkyl substitution on the amino nitrogen favoured selectivity for the soleus muscle more than cycloalkyl substitution did. PMID- 2877895 TI - Effect of antiandrogens on the hypothalamic gamma-aminobutyric acid (GABA) and glutamate contents of the Indian palm squirrel (Funambulus pennanti, Wroughton). AB - Intramuscular administration of 20 mg/kg flutamide (Flut) or 50 mg/kg of cyproterone acetate (CPA) daily for a period of three weeks significantly elevated the hypothalamic GABA content. CPA is found to decrease the hypothalamic glutamate level while Flut elevated it. Both, Flut and CPA reduced the hypothalamic weight. PMID- 2877894 TI - Low-dose infusion of somatostatin in man--no effect upon intestinal calcium absorption but a fall in blood insulin. AB - We studied the role of low plasma somatostatin (SRIF) levels in intestinal calcium absorption (CaA) in man. Plasma somatostatin-like immunoreactivity (SLI; pg X ml-1) rose after a 600-cal test meal (from 22.9 +/- 2 basally to 30.6 +/- 3.6 at 45 min, p less than 0.05), but was not affected by an oral Ca load (264 mg). Under intravenous SRIF (0.15 microgram kg-1 h-1) plasma SLI rose from 3.3 +/ 0.4 basally to 24.5 +/- 3 at 45 min (p less than 0.001). CaA was not influenced under these conditions, whereas insulin levels fell significantly and the levels of PTH, calcitonin, glucagon and GH were not changed. A regulating role of SRIF in CaA seems therefore unlikely for human physiology, since neither SLI is influenced by an oral Ca load, nor is CaA changed under postprandial SLI. The fall in insulin under postprandial-like SLI levels favors the view of a hormonal role of SRIF in man. PMID- 2877896 TI - A preadipocyte clonal line from mouse brown adipose tissue. Short- and long-term responses to insulin and beta-adrenergics. AB - A clonal cell line has been established from the interscapular brown adipose tissue (BAT) of the C57 BL/6J +/+ mouse. The line, designated BFC-1, is aneuploid and exhibits both morphological and biochemical properties characteristics of mature adipocytes. Adipose conversion begins after confluence and is accompanied by an early emergence of lipoprotein lipase; a later emergence of glycerol-3 phosphate dehydrogenase and acid: CoA ligase; an increase in the average triglyceride content. Adipose conversion, estimated by activities of enzyme markers, is enhanced at any given time by the continuous presence in the culture medium of insulin and triiodothyronine, both within their physiological range of concentrations. In addition to both hormones, chronic exposure of confluent cells to beta-adrenergics brings similar long-term effects on adipose conversion. The uptake of labelled 2-deoxyglucose by differentiated BFC-1 cells is stimulated by insulin; the half-maximum effect is observed at 1 nM insulin. Differentiated BFC 1 cells, in which endogenous triglycerides have been prelabelled on the fatty acid moiety, do respond to beta-adrenergics by releasing radioactive fatty acids. The agonist potency order and the EC50 value for each agonist are BRL 37344 (0.5 nM) greater than isoproterenol (1.5 nM) greater than norepinephrine (3 nM) greater than epinephrine (7 nM) greater than salbutamol (15 nM). The half maximally and maximally effective concentrations of corticotropin to stimulate lipolysis are found to be 4 and 100 nM, respectively. The lipolytic response to isoproterenol is counteracted by prior addition of insulin or simultaneous addition of propranolol. Parallel studies performed on Ob17 cells, a clonal line established from mouse white adipose tissue (Negrel et al., Proc natl acad sci US 75 (1978) 6054), show that the agonist potency order and the EC50 value for each agonist are BRL 37344 (3 nM) greater than isoproterenol (10 nM) greater than norepinephrine (20 nM) greater than epinephrine (40 nM). Thus both BFC-1 cells and Ob17 cells show an atypical beta-adrenoreceptor similar to that described in rat adipocytes (Arch et al., Nature 309 (1984) 163), but the sensitivity of BFC-1 cells toward beta-agonists is found to be 6-fold higher than that of Ob17 cells. Thus the BFC-1 line represents a useful model for the study of short- and long term responses to beta-adrenergics. PMID- 2877898 TI - Is chronic hypoxaemia and/or hypercapnia of the obstructive patient reversible? The role of almitrine bismesylate. PMID- 2877897 TI - Modulation of transglutaminase activity in mononuclear phagocytes and macrophage like tumor cell lines by differentiation agents. AB - The effect of glucocorticosteroids, retinoids, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and the tumor promoter phorbol myristate acetate (TPA) on the expression of transglutaminase activity in vitro differentiating bone marrow derived mouse and rat mononuclear phagocytes (BMDMP) and mouse and human myeloid leukemia cell lines was assessed. Dexamethasone was found to induce an increase of about 100% in transglutaminase activity in mouse and rat BMDMP. The effect was time- and dose-dependent, and specific for steroids with glucocorticoid activity. Retinoic acid (RA) suppressed transglutaminase activity in mouse BMDMP (approximately 50%) and enhanced it in rat BMDMP (100-200%). Other retinoids were less effective. 1,25(OH)2D3 had little effect on transglutaminase expression in mouse BMDMP and suppressed it in rat BMDMP (approximately 60%). TPA exerted a suppressive effect (approximately 50%) on transglutaminase activity of both rat and mouse BMDMP. In murine (P388D1 and J774.2) and human (ML3, HL-60, KG-1, HEL, U937) myeloid leukemia cell lines, dexamethasone enhanced transglutaminase activity to a varying degree (100-1,000%), RA suppressed it in P388D1 cells (approximately 70%) and enhanced it in the other cell lines (100-1,500%), 1,25(OH)2D3 induced a rather small augmentation of enzyme expression, whereas TPA suppressed enzyme expression (70-100%). The species-specific differences previously observed by us for the effect of RA, dexamethasone and 1,25(OH)2D3 on the formation of BMDMP from mouse and rat bone marrow progenitor cells are now shown to extend also to effects on expression of transglutaminase activity. From a mechanistic point of view it is of interest that dexamethasone uniformly enhanced transglutaminase activity, whereas TPA suppressed it. RA and 1,25(OH)2D3 induced either suppression or enhancement in the various cell types, with no correlation between the direction of the effect of the two agents. The data suggest that modulation of transglutaminase activity by the four agents occurs via disparate mechanisms. PMID- 2877899 TI - Deep prepyriform cortex kindling and its relation to amygdala kindling in the rat. AB - Kindling of the deep prepyriform cortex (DPC), a recently identified sensitive site to chemoconvulsants, was compared to kindling of the amygdala in rats. Although the two kindled sites were very similar in their initial responses, electroencephalographic changes during kindling stimulation, kindling seizure development, and growth of afterdischarge, they differed in that the deep prepyriform cortex showed a significantly lower final threshold, a significantly higher frequency of afterdischarge and a significantly shorter latency to bilateral forelimb clonus than the amygdala. Significant bidirectional transfer was found during secondary kindling of either of the two sites, suggesting a close interrelation between them. Rhythmic synchronous discharge was directly induced in the deep prepyriform cortex by ipsilateral amygdala stimulation, but not in the amygdala by ipsilateral cortical stimulation. Local application of both muscimol (0.45 nM) and 2-amino-5-phosphonovaleric acid (25 nM) into the cortical site reduced the afterdischarge duration of amygdala-kindled seizures by approximately 20% without changing the type or duration of the motor seizure. We suggest that the deep prepyriform cortex is "downstream" from the amygdala in the preferential routes of afterdischarge propagation, and that, although the deep prepyriform cortical neurocircuits of GABA and excitatory amino acids may be involved in the maintenance of amygdala-kindled, self-sustained afterdischarge, they are not essential in the expression of amygdala-kindled motor convulsions. PMID- 2877900 TI - Chronic cocaine administration depletes tyrosine hydroxylase immunoreactivity in the rat brain nigral striatal system: quantitative light microscopic studies. AB - Chronic administration of cocaine (10 mg/kg, i.p., every 12 h for 10 consecutive days) produced a large decrease in tyrosine hydroxylase-staining axons and terminal boutons in the caudate nucleus in rats when examined 60 days after the final cocaine injection. This effect was quantitated using the Leitz data acquisition and display system (DADS) which revealed that there was a 63% decrease in tyrosine hydroxylase-positive processes in the caudate nucleus. In addition, this cocaine treatment regimen produced a large decrease in the number of tyrosine hydroxylase-positive staining neuronal perikarya in the pars compacta of the substantia nigra. Use of the Leitz-DADS system revealed that there was a 51% decrease in tyrosine hydroxylase-positive material in the substantia nigra. These data demonstrated that chronic administration of cocaine produced a long term loss of tyrosine hydroxylase in both the cell bodies of the substantia nigra and the nerve terminals of the caudate nucleus. Further studies are required to determine whether the observed changes are due to degeneration of the neurons or some metabolic effect. PMID- 2877901 TI - Purification by high performance liquid chromatography of Clostridium perfringens type A enterotoxin prepared from high toxin producers selected by a toxin antitoxin halo. AB - High enterotoxin-producing substrains of Clostridium perfringens type A were selected reproducibly as colonies having toxin-antitoxin haloes on agar plates of Duncan-Strong medium containing antitoxin serum. Enterotoxin from these substrains was subjected to rapid purification by high performance liquid chromatography (HPLC). For this, the toxin was extracted by sonication from sporulating bacteria grown in Duncan-Strong sporulation medium, fractionated by ammonium sulfate (40% saturation) precipitation and differential solubilization and then purified by HPLC: gel permeation chromatography through a G2000SW column and ion-exchange chromatography on a Mono Q column. Purified toxin preparations had a similar specific activity (4.2 X 10(2) mouse MLD/mg protein) and homogeneity on polyacrylamide gel-electrophoresis to preparations obtained by conventional gel permeation through a Sephadex-G200 column. By further HPLC on a Mono Q column, minor nontoxin proteins were separated from the toxin without loss of the toxicity on a protein basis. The final yield of the purified toxin was about 15% of that in the bacterial extract. The two HPLC procedures each took only one hour. PMID- 2877902 TI - A gamma 3 hinge region probe: first specific human immunoglobulin subclass probe. AB - We report the first specific human immunoglobulin subclass probe which was obtained by subcloning the gamma 3 hinge region. This specific gamma 3 probe allowed us to identify with certainty the C gamma 3 gene on Southern genomic blots, to describe the first C gamma 3 restriction fragment length polymorphism (EZZ gamma 3 RF) and to show that an IgG3 selective deficiency, previously described serologically, was not due to a deletion of the C gamma 3 gene. Such a probe should be particularly useful for screening libraries from individuals with IgG3 immunodeficiencies or presenting unusual C gamma 3 genes and, consequently, for studying the C gamma gene evolution. PMID- 2877903 TI - Atrial natriuretic factor receptors and stimulation of cyclic GMP formation in normal and malignant osteoblasts. AB - Synthetic rat atrial natriuretic factor (Ile-ANF-26) stimulated cyclic GMP formation by up to several hundred-fold in osteoblast-rich cultures from newborn rat calvaria and in clonal osteogenic sarcoma cells (UMR 106-01) which are phenotypically osteoblast. ANF had no effect on the cyclic AMP response to parathyroid hormone in the same cells. Specific, high-affinity binding sites for ANF were identified in both cell types, with Kd and receptor numbers in normal osteoblasts of 1.2 +/- 0.1 X 10(-10) M and 42 +/- 4 X 10(3) per cell, and in UMR 106-01 cells of 1.4 +/- 0.1 X 10(-10) M and 22 +/- 4 X 10(3) per cell. PMID- 2877904 TI - Successful treatment of oligospermic and azoospermic men with alpha 1-blocker and beta-stimulator: new treatment for idiopathic male infertility. AB - We studied the effect of oral administration of alpha 1-blocker and beta stimulator on 20 idiopathically infertile men. Bunazosin (alpha 1-blocker, 2 mg/day) and procaterol (beta-stimulator, 100 micrograms/day) were given orally twice daily for 5 months. The administration of alpha 1-blocker and beta stimulator elicited an increase in sperm output and seminal volume in 16 patients (80%). The increase in sperm output seems to be associated with relaxations of myoid cells, which lead to dilatation of stenotic areas of seminiferous tubules, occurring discontinuously, and subsequent maintenance of good tubular fluid flow. No adverse effects were observed in this series. PMID- 2877906 TI - [Phorbol ester or diacylglycerol modulates somatostatin binding to its receptors on rat pancreatic acinar cell membranes]. AB - To clarify the precise mechanism by which unrelated peptides, cholecystokinin or carbamylcholine, modulate the somatostatin binding, the effect of a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) or a synthetic diacylglycerol analog, 1-oleyl-2-acetylglycerol (OAG) on [125I-Tyr1]somatostatin binding to pancreatic acinar cell membranes was examined. Pretreatment of pancreatic acini for 120 min at 37 degrees C with 100 ng/ml TPA maximally reduced subsequent labeled somatostatin binding to acinar membranes. The inhibitory effect of TPA on the somatostatin binding was dependent on the dose used, or the time and temperature of pretreatment. These effects of TPA were almost mimicked by the treatment of acini with OAG. Scatchard analysis of [125I-Tyr1]somatostatin binding demonstrated that the decrease in the labeled somatostatin binding induced by TPA or OAG pretreatment was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. A specifically labeled single band of the Mr = 90 K obtained with a photoaffinity cross-linking study indicates that the somatostatin binding sites are the same somatostatin receptor as previously described. Moreover, the intensity of the Mr = 90 K band was dramatically decreased when acini were treated with increasing concentrations of TPA, a finding consistent with TPA-induced decrease in binding capacity. Such an inhibitory effect of TPA was abolished when pretreatment of acini with TPA was performed in the presence of Ca2+ chelating compounds such as EDTA and EGTA. Interestingly, the combined treatment of TPA and Ca2+ ionophore A23187 caused synergistic inhibition of the subsequent labeled somatostatin binding to acinar membranes, although Ca2+ ionophore itself almost failed to affect the somatostatin binding. These results suggest, therefore, that TPA or OAG can modulate somatostatin binding to its receptors on rat pancreatic acinar cell membranes, presumably through activation of Ca2+-activated, phospholipid dependent protein kinase (protein kinase C) and the activated protein kinase C and intracellular Ca2+ mobilization presumably act to modulate pancreatic acinar somatostatin receptors synergistically. PMID- 2877905 TI - [Prolonged excitation of individual neocortical neurons. Structure of spontaneous firing]. AB - Spontaneous firing of single neurons was studied during L-glutamate-induced stable activation in the cat cerebral cortex. The autocorrelation analysis of the trains of discharges showed, that periods of increased and decreased probability of discharges were constant in general. A single neuron seems incapable of radically affecting the interneurons connected with it. The type of spontaneous firing is mainly associated with the level of activation of the neuronal assembly where the neuron belongs. PMID- 2877907 TI - [CCK and carbachol differently modulate somatostatin binding to rat pancreatic acinar membranes]. AB - Somatostatin binding to its receptors on rat pancreatic acinar membranes was characterized with [125I-Tyr1]somatostatin. The COOH-terminal octapeptide of cholecystokinin (CCK8), when present at various concentrations in the reaction mixture for the binding study, reduced labeled somatostatin binding in a dose dependent manner, whereas carbachol or Ca2+ ionophore did not affect the binding. By contrast, when pancreatic acini were first treated with carbachol and thereafter [125I-Tyr1]somatostatin binding to membranes prepared from these acini was examined, carbachol reduced subsequent somatostatin binding in a dose dependent manner. Scatchard analysis of the labeled somatostatin binding revealed that carbachol pretreatment decreased the maximum binding capacity from 142 +/- 20 fmol/mg of membrane protein to 63.5 +/- 3.5 fmol/mg of membrane protein without significantly affecting the binding affinity. To test for the possibility that CCK8 also may affect labeled somatostatin binding through an intracellular process, pancreatic acini were first treated with CCK8 and then the membrane bound CCK8 was washed out. Subsequent labeled somatostatin binding to membranes from these acini was also decreased. When 1 mM EDTA was present in the pretreatment medium, the inhibitory effect of carbachol or CCK8 was partially abolished, suggesting that an intracellular process to modulate somatostatin binding is dependent on Ca2+. On the other hand, pretreatment of acini with Ca2+ ionophore almost failed to affect subsequent labeled somatostatin binding. Results therefore suggest that CCK8 can modulate labeled somatostatin binding to pancreatic acinar membranes not only acting through an intracellular process but also at membrane sites and carbachol- or CCK8-activated intracellular process to modulate somatostatin binding is dependent on Ca2+, but Ca2+ mobilization itself is not sufficient to affect subsequent somatostatin binding. PMID- 2877908 TI - Evaluation of testicular hCG binding in unilaterally cryptorchid rats following administration of ethane dimethane sulphonate (EDS). AB - Administration of ethane dimethane sulphonate (EDS) (75 mg/kg) to unilaterally cryptorchid rats, results in a rapid decline in serum testosterone levels and a marked reduction in hCG binding to homogenates of scrotal and cryptorchid testes, consistent with the destruction of Leydig cells within the testes as shown by morphological and morphometric analysis. Between 3 and 7 days after EDS, serum LH and FSH levels rise, LH to levels found in castrate rats. hCG binding begins to recover in scrotal testes, reaching 32% of control values 28 days after EDS. However, the recovery of hCG binding to cryptorchid testes is more rapid, reaching 51% of control levels by 21 days which coincides with the re establishment of serum testosterone to normal levels. Since a different rate of recovery is observed for hCG binding to scrotal and cryptorchid testes, and both testes are exposed to the same circulating levels of LH and FSH, the likely stimulus for recovery of hCG binding and regeneration of Leydig cells is intratesticular in origin. This supports the concept that local factors, released following damage to the seminiferous epithelium by cryptorchidism, play a role in the differentiation and growth of Leydig cells within the testis. PMID- 2877909 TI - Characteristics of the beta-adrenergic receptor in the rat ventral prostate using [125I]cyanopindolol. AB - The binding characteristics of the beta-adrenergic receptor in the rat ventral prostate homogenate have been studied using the highly potent beta-adrenergic antagonist [125I]cyanopindolol (CYP) as ligand. The bound ligand was separated from the free moiety by precipitation with polyethylene glycol (PEG-6000). This technique is simple, accurate, fast and more advantageous than filtration of the hormone-receptor complex on glass fiber filters or direct centrifugation. [125I]CYP binds to a single class of high affinity sites at an apparent KD value of 23 pM. Using 0.1 microM (-)propranolol to determine non-specific binding, a number of sites of 600 fmol/mg protein were measured. The observed order of potency of adrenergic agonists (KD values) in competing for [125I]CYP binding was: (-)isoproterenol (25 nM) greater than (-)epinephrine (74 nM) much greater than (-)norepinephrine (1900 nM). Detailed study of the binding potency of a large series of beta 1- and beta 2-adrenergic agonists and antagonists showed the presence of a typical beta 2-subtype adrenergic receptor in the rat ventral prostate. The best estimate indicates that the proportion of beta 2-adrenergic receptors in rat ventral prostate is more than 95% of the total population of beta-adrenergic receptors in this tissue. The high selectivity and density of beta 2-adrenergic receptors in rat ventral prostate suggest a physiological role of circulating and/or locally secreted catecholamines in the control of prostatic growth and function. PMID- 2877910 TI - Acute dystonic reaction to bethanechol--a direct acetylcholine receptor agonist. AB - Bethanechol is a direct agonist of the acetylcholine receptor that was recently introduced in the therapy of gastro-oesophageal reflux. Acute dystonic reactions to bethanechol were observed in a 10-month-old infant who also demonstrated similar dystonic reactions to dopamine receptor blocking agents of two different classes. This first report of acute dystonic reaction to cholinergic agonists in human is in accord with the current theories of the role of acetylcholine and dopamine in the pathogenesis of acute dystonic reactions. PMID- 2877911 TI - Neural and paracrine regulation of gastrin release using rat antral mucosa in tissue culture--the effect of carbachol, bombesin, and anti-somatostatin antibody on gastrin release. AB - Gastrin release was significantly stimulated by the cholinergic agent carbachol at doses of 10(-4) M, 10(-5) M, and 10(-6) M. Peak stimulation was observed at 10(-5) M. Gastrin release was also significantly stimulated by bombesin at a dose of 10(-8) M, and 10(-6) M atropine which abolished the effect of carbachol in stimulating gastrin release had no effect on the bombesin-stimulated gastrin release. In addition, anti-somatostatin antiserum significantly stimulated gastrin release. These findings suggest that gastrin release is regulated by cholinergic and noncholinergic neurons the latter being thought to be a bombesin containing neuron, and that antral somatostatin exerts a continuous restraint on gastrin release by the paracrine mechanism. PMID- 2877912 TI - A multicenter, double-blind, randomized, placebo-controlled comparison of nocturnal and twice-a-day famotidine in the treatment of active duodenal ulcer disease. AB - The efficacy and safety of famotidine, a potent new long-acting H2-receptor antagonist, was compared with placebo in a multicenter, double-blind, randomized, placebo-controlled study in the United States. A total of 384 patients with endoscopically proven acute duodenal ulcer disease were enrolled. Patients received either famotidine or a placebo. The patients receiving famotidine were treated with one of three dose regimens, 40 mg h.s., 40 mg b.i.d., or 20 mg b.i.d. Patients were reassessed by endoscopy at 2, 4, and 8 wk if ulcer healing had not occurred sooner. A diary was kept to record the duration and intensity of the day and night pain and the amount of Gelusil antacid (Parke-Davis, Morris Plains, N.J.) ingested. Three hundred sixty-three patients met the evaluation criteria. The results revealed a 4-wk healing rate of 70%, 75%, 67%, and 31% for the famotidine 40 mg h.s., 40 mg b.i.d., 20 mg b.i.d., and placebo groups, respectively. The 8-wk healing rates for the same respective groups were 83%, 82%, 82%, 45%. Ulcer pain and antacid consumption occurred less often in the famotidine groups. The clinical and laboratory safety profile of the famotidine groups was similar to that of the placebo group. Famotidine appears to be an effective and safe once-a-day therapy for the treatment of acute duodenal ulcer disease. The recommended dosage is 40 mg h.s. PMID- 2877913 TI - Tetanic stimulation-induced changes in [3H]glutamate binding and uptake in rat hippocampus. AB - Tetanus-induced (400 Hz, 200 pulses) long-lasting potentiation of the stratum radiatum-evoked CA1 population spike in hippocampal slices is not accompanied by any change in Na+-independent [3H]glutamate binding sites. Homosynaptic depression that occurs subsequent to either a low frequency tetanus (20 Hz, 600 pulses) or a transient exposure to Cl(-)-free (containing NO3-) medium is associated with an elevation in the amino acid binding. [3H]Glutamate uptake into slices was decreased following a high frequency (400 Hz, 200 pulses) tetanus but in the majority of cases was increased following a low frequency (20 Hz, 600 pulses) tetanus to stratum radiatum. When the high frequency tetanus was given in the absence of extracellular Ca2+, there was a further reduction in [3H]glutamate uptake. PMID- 2877914 TI - Immunohistological detection of methionine-enkephalin-like and endorphin-like material in the digestive tract and in the nervous system of the mussel: Mytilus edulis L. AB - Using the indirect immunofluorescence technique, methionine-enkephaline-like, alpha- and beta-endorphin-like peptides were detected on whole body sections of Mytilus edulis L. Met-enkephalin-like immunoreactivity was localized in the epithelium of the digestive tract, in the hepatopancreas, and in the nervous system. The immunoreactive cell bodies were very abundant in the anterior gastric epithelium, but sparse in the terminal portion of the digestive tract. By their basal processes the immunoreactive cells were in contact with a plexus of immunoreactive cells and fibers located in the connective tissue underlying the digestive epithelium. In the principal hepatopancreatic ducts, isolated cells showing met-enkephalin-like immunoreactivity were detected between the epithelial cells and the basal lamina. A few immunoreactive cells and fibers were observed between the hepatopancreatic tubules. The three pairs of nervous ganglia contained in their cortical layer numerous met-enkephalin-like immunoreactive perikarya. Their central area possessed fluorescent immunoreactive bundles of fibers extending to the commissures, the connectives, and the nerves. Met enkephalin-like immunoreactive fibers were detected between the smooth muscle cells. At the surface of these smooth muscle cells, immunopositive met-enkephalin like tapered nervous endings were observed. The alpha- and beta-endorphin antisera produced a positive immunoreaction in some gastric epithelial cells, in some perikarya of the pedal ganglia, and in some nervous fibers. The endorphin like structures were far less abundant than the met-enkephalin-like structures, but very close to them. PMID- 2877915 TI - Control of prolactin secretion in birds: a review. PMID- 2877916 TI - Cardiovascular responses to neurohormones in conscious chickens and ducks. AB - Cardiovascular responses (cardiac frequency, fH; mean arterial pressure, Pa; ischiatic arterial blood flow; Qi; ischiatic vascular resistance, Ri) to 1 norepinephrine (NE), acetylcholine (ACH), [Asp1, Val5]-angiotensin II (ANG II), and arginine vasotocin (AVT) were studied in conscious chickens (Gallus gallus) and Pekin ducks (Anas platyrhynchos). Age-dependent changes, in the cardiovascular variables and the responses to the native avian neurohormones, were also studied in ducks. NE injection caused larger increases in Pa and Ri, and a greater associated fall in fH, in ducks than in chickens. The pressor effect of ANG II was more persistent and developed at a slower rate than the response to NE in both species, although the pressor effect was greater in ducks. Interestingly, ANG II injection caused a tachycardia in these baroreceptor-intact birds. ACH and AVT produced similar rapid falls in Pa and a corresponding tachycardia in both species, although the fH response was greater in ducks. ANG II rapidly increased NE concentration in the arterial plasma of adult ducks, while AVT increased epinephrine (E) concentration. Resting Pa and hematocrit were lower, and fH was higher, in immature ducks. Immature ducks also were less responsive than adults to the cardiovascular actions of NE, ACH, AVT, and ANG II. The results demonstrate differences in the cardiovascular responses to neurohormones in chickens and ducks consistent with a higher level of cardioinhibitory nervous tone and a greater sensitivity to sympathetic stimuli in the aquatic species, which increase during maturation. PMID- 2877917 TI - Direct control of the gonadotroph in a teleost, Poecilia latipinna. II. Neurohormones and neurotransmitters. AB - Pituitaries from male and female mollies were incubated with varying amounts of mammalian LH-RH, arginine vasotocin, dopamine, or serotonin for 18 hr. Ultrastructural differences between control and experimentally treated glands were used to define the direct effects of these neurohormones and neurotransmitters on the gonadotrophic cells of the adenohypophysis. The effects varied in intensity according to the sex and reproductive state of the donor animal. LH-RH stimulated gonadotrophin secretion by the gonadotrophs, as did vasotocin, although to a much lesser extent and with noticeable differences between the sexes. Dopamine inhibited secretion by basally active gonadotrophs and probably from active cells also, although to a lesser extent. Serotonin mildly stimulated secretion at all stages in both sexes. The results of this study indicate the possible involvement of neurohypophysial octapeptides and of monoamines in the direct control of the gonadotroph of Poecilia latipinna. PMID- 2877918 TI - In vitro effects of somatostatin and urotensin II on prolactin and growth hormone secretion in tilapia, Oreochromis mossambicus. AB - The control of release of two recently characterized forms of prolactin (PRL) of molecular mass 24 and 20 kDa was investigated. The rostral pars distalis of male tilapia was incubated singly in a hypotonic modified Krebs-Ringer bicarbonate medium in order to stimulate PRL release; for comparison, the proximal pars distalis containing growth hormone (GH) cells was incubated in isotonic medium with or without 1 microgram/ml cortisol to stimulate GH release. The release of both PRLs and GH into the medium was measured by sodium dodecyl sulfate (SDS)- polyacrylamide gel electrophoresis followed by densitometry. Both somatostatin and synthetic (Gillichthys) urotensin II, a partial somatostatin homolog and analog from the teleost caudal neurosecretory system, significantly inhibited the release of both PRLs. Somatostatin significantly inhibited GH release, but urotensin II had no significant effect. PMID- 2877919 TI - Characterization of coho salmon (Oncorhynchus kisutch) islet somatostatins. AB - Three different somatostatins have been isolated from the pancreatic islet tissue of the coho salmon (Oncorhynchus kisutch) by gel filtration and HPLC. Two of these peptides contain 14 amino acids and the larger third peptide consists of 25 amino acids. The sequence of the salmon SST-25 is Ser-Val-Asp-Asn-Leu-Pro-Pro-Arg Glu-Arg-Lys-Ala-Gly -Cys-Lys-Asn-Phe-Tyr-Trp-Lys-Gly-Phe-Thr-Ser-Cys. The sequence of the salmon SST-14-I is Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe Thr-Ser-Cys. The other small somatostatin (SST-14-II) which was not sequenced has an amino acid composition identical to the C-terminal 14 amino acids of the SST 25 and it is probably derived from this larger form. Evidence for low levels of a somatostatin containing 28 amino acids is also presented. This SST-28 appears to be an N-terminal extended precursor of SST-25 or a peptide derived via alternative processing of a common preprosomatostatin. Injected into juvenile salmon, SST-25 caused a decline in circulating levels of plasma insulin, depletion of liver glycogen, and activation of lipolytic pathways. Juvenile salmon treated with anti-SST-25 serum revealed elevated levels of plasma insulin as well as an increase of the glycogen content of the liver. PMID- 2877920 TI - Effectiveness of somatostatin in regulating pancreatic splenic lobe hormone secretion following 99% pancreatectomy in adult chickens. AB - In vivo studies were carried out in adult chickens in an attempt to evaluate the effectiveness of somatostatin (SRIF) in regulating hormone secretion from the splenic pancreatic lobe after 99% of the pancreatic mass was surgically ablated. Sixteen days after either sham operation or 99% pancreatectomy, birds were infused iv with SRIF (420 ng/min) alone and then glucose (59 mg/Kg/min) was superimposed on the infusate, or birds were infused iv with glucose alone and then SRIF was superimposed on the infusate. Serial blood samples were taken during the 16-day postoperative period and also at regular intervals during the 75-min observation period. Plasma was analyzed for glucose, insulin (IRI), glucagon (IRG), pancreatic polypeptide (IRAPP), and somatostatin (IRSRIF). Careful standardization of the SRIF radioimmunoassay, as well as analysis of the molecular form of circulating SRIF, indicated that "true" SRIF levels were being estimated in plasma of both groups of chickens. Normal-fed chickens have plasma SRIF levels of 1.12 +/- 0.07 ng/ml which increases 16 days after 99% pancreatectomy to 2.39 +/- 0.15 ng/ml plasma. The latter decreases by 55% with an overnight fast. Glucose infusion, superimposed upon a preexisting SRIF infusion in adult chickens, did not evoke an IRI response in the 99% depancreatized birds equal to that observed in sham-op controls. Although a full SRIF dose-response curve was not generated, the glucose data strongly suggest a reduced sensitivity of insulin-secreting cells to SRIF in pancreoprivic birds. Both bird groups were equally--and markedly--sensitive to the IRG-depressant effects of SRIF; in contrast, the depancreatized chickens were significantly more resistant to the APP-inhibitory effects of SRIF when compared to the sham-op control birds. Thus, 16 days after partial pancreatectomy, the hormone-release mechanisms appeared altered for IRI and IRAPP in response to SRIF. Data obtained when glucose infusions preceded SRIF infusions indicated that A-cell release of glucagon was much more sensitive to glucose (as a depression) in the partially depancreatized birds than in control birds. These same birds were significantly less responsive to the glucose-depressant effect on plasma APP levels. Thus, it appears that 99% pancreatectomy increases the sensitivity of the SRIF, IRI, and IRG release mechanisms in response to glucose 16 days after surgery. The insulin-to-glucagon (I/G) molar ratios indicative of metabolic anabolism can still be achieved by nutrients 16 days after partial pancreatectomy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2877921 TI - Estimation of linkage disequilibrium from conditional haplotype data: application to beta-globin gene cluster in American blacks. AB - Simple estimators of gene frequencies and linkage disequilibria are proposed when haplotype data are available from four parental chromosomes of a child (or fetus) for whom genetic counseling is sought for a disease condition. The method is illustrated with restriction site polymorphisms associated with sickle-cell anemia (Hb-beta S) gene as surveyed in genetic counseling data from American blacks. The method suggested here is shown to be useful in testing for the significance of interactions of site-specific variations of any order in the chromosomal region assayed. PMID- 2877922 TI - Monkey erythropoietin gene: cloning, expression and comparison with the human erythropoietin gene. AB - The erythropoietin (Epo) gene from Cynomolgus monkeys has been isolated from a kidney cDNA library using mixed 20-mer oligodeoxynucleotide probes. The gene encodes a 168 amino acid (aa) mature protein with a calculated Mr of 18,490 and a presumptive signal peptide of 24 aa. The Epo gene, when transfected into Chinese hamster ovary (CHO) cells, produces a glycosylated protein with an apparent Mr of 34,000. The expressed product is biologically active in vivo. The monkey gene exhibits 92% and 94% homology to the human gene at the aa and nucleotide sequence levels, respectively. When compared with the human Epo, monkey Epo has an additional 3-aa residue at the N terminus of the mature protein and a deletion of an internal lysine residue. PMID- 2877923 TI - APUD cells in the ovary of white rat. PMID- 2877924 TI - Mutagenicity studies of selected antihistamines, their metabolites and products of nitrosation. AB - Methapyrilene, four structurally related antihistamines, three metabolites of methapyrilene and two products of the reaction of methapyrilene with nitrite were all tested for mutagenicity to Salmonella typhimurium. The two products of the methapyrilene-nitrite reaction have also been identified as metabolites of methapyrilene. None was mutagenic alone, either with or without rat liver S-9 activation. After reaction with sodium nitrite in acetic acid solution (nitrosation), the products of five of the ten compounds were mutagenic. These compounds were methaphenilene, 2-thiophenemethanol, 2-thiophenecarboxylic acid, N (2-pyridyl)-N'N'-dimethylethylenediamine and N-(2-thenylmethyl)-2-aminopyridine. PMID- 2877925 TI - Recent developments in the field of marine natural products with emphasis on biologically active compounds. PMID- 2877926 TI - [Hypoxemic shock and the myocardium. Effect of cardiovasoactive substances on the course of shock]. PMID- 2877927 TI - [Long-term therapy with depot neuroleptics. Prevention of recurrence in chronic schizophrenic patients]. PMID- 2877928 TI - Adrenergic control of lipolysis and metabolic responses in obesity. AB - Adrenergic modulation of lipolysis was determined in obese and lean women. Epinephrine was infused alone, or in combination with propranolol, or with phentolamine. In both obese and lean subjects slight alpha- and prevalent beta adrenergic lipolytic responsiveness was observed. alpha-adrenergic blockade by yohimbine potentiated lipolysis and exercise energy expenditure. Yohimbine application during the slimming treatment increased weight loss without side effects. PMID- 2877929 TI - Absence of human chorionic somatomammotropin during pregnancy associated with two types of gene deletion. AB - Complete absence of human somatomammotropin (hCS) was demonstrated in two patients experiencing an otherwise uneventful pregnancy. After delivery, DNA was prepared from the neonate blood or from the placenta and the integrity of the hCS hGH gene cluster was investigated by Southern blotting and hybridization with an hCS cDNA probe. Patient 1 was found to be homozygous for a deletion involving hCS A, hGH-V, and hCS-B. Patient 2 was a double heterozygote, with one chromosome bearing the same deletion as that of patient 1, while in the other, only the hCS A gene was missing. Considerations relative to the frequency of the defect are derived from the present results. PMID- 2877930 TI - DNA finger printing by oligonucleotide probes specific for simple repeats. AB - Interspersed simple repetitive DNA is a convenient genetic marker for analysis of restriction fragment length polymorphisms (RFLPs) because of the numbers and the frequencies of its alleles. Oligonucleotide probes specific for variations of the GATCA simple repeats have been designed and hybridized to a panel of human DNAs digested with various restriction enzymes. Numerous RFLPs were demonstrated in AluI and MboI digested DNA with "pure" GATA oligonucleotides as probes. The optimal length of the probe for RFLP analysis was 20 bases taking into account fragment lengths (1.5-7 kilobases = kb), signal to background ratio, and number of clearly evaluable RFLPs. By using different restriction enzymes individual specific hybridization patterns ("DNA fingerprints") can be established. Hypervariable simple repeat fragments are stably inherited in a Mendelian fashion. Advantages of this method are discussed. PMID- 2877931 TI - The influence of low arylsulfatase A activity on neuropsychiatric morbidity: a large-scale screening in patients. AB - A total of 1728 patients consecutively admitted to a neuropsychiatric hospital and 379 chronically ill inpatients were examined for activity of arylsulphatase A (ASA) in leucocytes. A further 519 healthy individuals served as controls. We did not find evidence for the involvement of low ASA activity in chronic patients. The consecutive admissions showed a slight preponderance in the lower ASA activity classes. This activity range covers persons heterozygous for ASA deficiency alleles. The data are compatible with the hypothesis that carriers of low ASA activity alleles are at a slightly higher risk for neuropsychiatric disorders. PMID- 2877932 TI - A straightforward approach to isolate DNA sequences with potential linkage to the retinoblastoma locus. AB - From a human-Chinese hamster somatic cell hybrid a clone was derived containing chromosome 13 in duplicate as its only human material. This clone was used to construct a human chromosome 13-specific recombinant DNA-library. Overlapping Sau3AI DNA sequences (11.9-17.2 kb) from the cell hybrid were inserted into the lambda phage vector EMBL4. From eleven recombinants having a human insert thirteen putative unique DNA sequences were isolated and cloned into the plasmid vector pBR329. A human-mouse hybrid containing a human chromosome 13 with a deletion of 13q14 and lacking its undeleted homologue was constructed to be used in a selection procedure for DNA sequences belonging to band q14. Three probes originating from two different phages were assigned to 13q14 because they did not hybridise to DNA from this cell hybrid. One of these 13q14 probes detects a low frequency (2/44) MspI restriction fragment length polymorphism. The probes are now being used for screening a cosmid library to find adjacent polymorphic sequences with a RFLP information content suitable for application in the diagnosis of hereditary retinoblastoma. PMID- 2877933 TI - Regional localisations and linkage relationships of seven RFLPs and myotonic dystrophy on chromosome 19. AB - We have studied the genetic linkage relationships of seven DNA polymorphisms on chromosome 19, with each other and with the myotonic dystrophy locus. The DNA sequences were localised to various regions of the chromosome using translocations in somatic cell hybrids. These results provide the basis for a linkage map of most of chromosome 19, and suggest that the myotonic dystrophy locus is close to the centromere. PMID- 2877935 TI - Development of additional RFLP probes near the locus for Duchenne muscular dystrophy by cosmid cloning of the DXS84 (754) locus. AB - We have isolated 70kb of sequences surrounding probe 754 (DXS84), linked with Duchenne muscular dystrophy. In addition to the original PstI RFLP detected by 754, BglII and EcoRI RFLPs were detected with the single copy subclone 754.11 and a HindIII RFLP with the subclone 754.6. The BglII and HindIII and HindIII RFLPs both have minor allele frequencies of 40%, as in PstI polymorphism. The EcoRI polymorphism has a minor allele frequency of 23%. Since a linkage disequilbrium is observed between these RFLPs (P less than 0.001), the BglII and the HindIII RFLPs do not contribute to the heterozygosity. However, the minor allele of the EcoRI RFLP segregates exclusively with the major haplotype of the PstI-BglII HindIII complex, and consequently 47% of the homozygotes for the haplotype become heterozygous. As a result, the overall heterozygote frequency of the DXS84 locus increases from 50% to 65%. PMID- 2877937 TI - Heterogeneity in the map distance between X-linked agammaglobulinemia and a map of nine RFLP loci. AB - In nine family pedigrees in which X-linked agammaglobulinemia (XLA) is segregating, a multi-point linkage analysis has been carried out. In each family, the map distance, d, between XLA and a fixed point in a known map of nine RFLP loci on the X chromosome was estimated by calculating the log likelihoods, L(d). Using a new method, the 10-point likelihood was approximated by appropriately combining three 4-point likelihoods. Homogeneity tests (admixture tests) were performed showing clear evidence for heterogeneity of XLA. PMID- 2877934 TI - Linkage relationships of the insulin receptor gene with the complement component 3, LDL receptor, apolipoprotein C2 and myotonic dystrophy loci on chromosome 19. AB - Myotonic dystrophy is associated with disturbances in the insulin response, possibly due to an abnormality of the insulin receptor. Both the myotonic dystrophy (DM) and insulin receptor (INSR) genes are on chromosome 19. Using a cloned gene probe for INSR, we have studied its linkage relationships with the DM locus and other chromosome 19 markers. The results show that INSR is not closely linked to DM, but is located very close to C3, in the region 19pter-19p13.2. This implies that the basic genetic defect which causes DM is not directly responsible for the disturbed insulin response in these patients. PMID- 2877936 TI - Isolation of a random cosmid clone, cX5, which defines a new polymorphic locus DXS148 near the locus for Duchenne muscular dystrophy. AB - We have isolated a random cosmid cX5 (DXS148), which maps into a small Xp21 deletion associated with Duchenne muscular dystrophy (DMD), chronic granulomatous disease (CGD), retinitis pigmentosa (RP) and McLeod syndrome, cX5 maps proximally outside several other deletions associated with DMD, glycerol kinase deficiency (GK) and adrenal hypoplasia (AHC). The following order of loci is proposed: centromere-OTC-cX5 (DXS148)-754 (DXS84)-PERT87 (DXS164)/DMD-telomere. A subclone cX5.7, isolated from this cosmid, identifies an MspI RFLP, with a minor allele frequency of 35%. This probe forms an important adjunct to the existing RFLPs for family studies in Duchenne muscular dystrophy. PMID- 2877938 TI - Close linkage between X-linked ectodermal dysplasia and a cloned DNA sequence detecting a two allele restriction fragment length polymorphism in the region Xp11-q12. AB - EDA (ectodermal dysplasia, anhidrotic) is an X-linked recessive disorder characterized by hypohidrosis, hypoor anodontia, and hypotrichosis. A possible linkage between the gene for EDA and a number of restriction fragment length polymorphisms (RFLPs) spread over the X chromosome was investigated in two Danish families segregating EDA. No recombination between the gene for EDA and our probe pTAK8, which detects a two allele polymorphism in the region Xp11-q12, was found in nine informative meiotic events (seven of which are phase known), giving a maximal lod score of 2.41 at a recombination fraction of 0.00. This juxtacentromeric location of the gene for EDA agrees well with the linkage data obtained with the other markers used in this study. PMID- 2877939 TI - A DNA polymorphism of the apoprotein AII gene in hypertriglyceridaemia. AB - A polymorphism of the apolipoprotein AII gene (on chromosome 1) was investigated using genomic hybridisation analysis. The two common alleles at this locus were defined by MspI restriction fragments of 3.0 kilobase pairs (M3.0) and 3.7 kilobase pairs (M3.7) respectively. The M3.7 allele was significantly more common (P less than 0.02) in Caucasian subjects who were normo-lipaemic (34%, 20/59) than in those who were hypertriglyceridaemic (16%, 16/98). Serum triglyceride levels were measured in 126 Caucasian subjects with different combinations of disease-associated alleles at the ApoAII and ApoCIII gene loci. Mean serum triglyceride levels were found to be significantly higher (P less than 0.05) in subjects with disease-associated alleles of both the ApoCIII and ApoAII genes, compared with subjects with a disease-associated allele of one or neither locus. PMID- 2877940 TI - Beta-globin gene polymorphism in Saudis--triple Hpa I fragments. AB - In an attempt to investigate beta-globin gene polymorphism in the Saudi population, DNA samples were analysed using restriction endonucleases, Mst II and Hpa I. Both beta A and beta S genes showed extensive polymorphism and were found to be linked to 13.0 kb, 7.6 kb, 7.0 kb, and 5.6 kb Hpa I fragments. Three DNA samples out of a total of 436 analysed, had beta-globin gene linked to three Hpa I fragments of the sizes 13.0 kb, 7.6 kb, and 5.6 kb. In this paper we present our findings and discuss the possibility of multiple beta-globin loci. PMID- 2877941 TI - De novo mutation in hemophilia A established by DNA haplotype analysis and precluding prenatal diagnosis. AB - In a family with a single case of hemophilia A genetic counselling was requested by the pregnant aunt of the propositus. The haplotypes generated by two extra genic RFLPs, at DXS52 (St14/Taq1) and DXS15 (DX13/BglII), and one intragenic RFLP in F8C (647/BclI) indicated that: she was not a carrier; the case of hemophilia resulted from a de novo mutation in a grandfather's gamete. PMID- 2877942 TI - Chromosome assignment and restriction fragment length polymorphism analysis of the anonymous DNA probe B79a at 7q22 (HMG8 assignment D7S13). AB - The anonymous DNA fragment B79a, which had previously been located to chromosome 7cen-7q22, has been more accurately assigned to 7q22 by dosage analysis in a patient hemizygous for a deletion of that region. By examination of a panel of genomic DNAs from unrelated individuals, digested with a number of different restriction enzymes, we have identified two frequent RFLPs detected by B79a. This probe will be important in the analysis of cystic fibrosis which has been mapped to the region around 7q22. PMID- 2877944 TI - Exon-specific oligonucleotide probes localize HLA-DQ beta allelic polymorphisms. AB - The HLA genetic region consists of a large multigene complex which includes a number of highly homologous alpha and beta genes encoding class II polypeptides, clustered in three major loci, DP, DQ, and DR. Analysis of genomic polymorphisms at each of these loci is of considerable interest due to the role of particular structural polymorphisms in immune function, but this analysis has been hampered by difficulty in distinguishing between such highly homologous loci. We have identified locus-specific and exon-specific class II gene sequences in order to produce synthetic oligonucleotide probes which hybridize specifically to DQ beta genes. Two such oligonucleotide probes are described which are specific for the beta 1 and beta 2 exons of DQ (DC) beta, which identify DQ beta genes in digests of cellular DNA and which can be used to characterize restriction sites flanking the two oligonucleotide-specific regions. By sequentially hybridizing these probes in modified Southern analyses, we have been able to generate a tentative "restriction map" of a newly identified DQ beta allele from digests of total genomic DNA. This oligonucleotide mapping technique discriminates between two HLA DQw3+ alleles, DQ3.1 and DQ3.2, permitting the recognition of structural polymorphisms with DQ beta which are highly associated with type I diabetes mellitus. PMID- 2877943 TI - Molecular characterization of a subtype of DQw1 recognized by hapten-specific T cells. AB - Previous studies of HLA-restricted antigen recognition by cloned T cells have frequently demonstrated reactivity that did not correlate precisely with the expression of serologically defined HLA specificities. To further explore such discrepancies, we utilized monoclonal antibody (MoAb) blocking, partial NH2 terminal amino acid sequencing, and Southern blot hybridization techniques to analyze the fine specificity of four autologous trinitrophenyl-specific T cell lines restricted to DR2-linked epitopes. MoAb blocking studies demonstrated that two of these lines recognized determinants on DR molecules while the other two recognized determinants on the same molecule that expresses the DQw1 determinant. However, these latter two lines appeared to recognize a DQw1-related determinant found primarily in association with DR2, but not the other DQw1-associated DR alleles, DR1 and DRw6. To ascertain whether these lines were defining a functional split of DQw1, we performed partial NH2-terminal amino acid sequencing of the molecules precipitated with a DQw1-specific MoAb (Genox 3.53) from different stimulator lines. The results showed that these T cell lines recognized a subtype of DQw1 that is in linkage disequilibrium with DR2. Moreover, we identified characteristic restriction fragment length polymorphisms with a DQ beta-specific cDNA that correlated with stimulatory capacity for the DQw1 restricted lines. These results demonstrate that: DQ molecules may provide restriction determinants that are incorrectly assigned to DR molecules on stimulator panel analyses; cloned antigen-specific T cell lines recognize polymorphic regions of class II molecules not distinguished by either conventional typing antisera or xenogeneic MoAb; and the DQw1 epitope(s) is located on a heterogeneous group of DQ molecules that differ from each other in the primary sequence of their beta chains. PMID- 2877945 TI - Molecular genotyping of human T-cell antigen receptor variable gene segments. AB - The gene complex encoding the beta chain of the T-cell antigen receptor (Tcr) in man was previously reported to contain a restriction fragment length polymorphism (RFLP) involving a single Bgl II site adjacent to the second constant region gene. This RFLP allowed assignment of Tcr beta genotypes in certain human families. In the present study, two different RFLP in a V beta gene family were detected using the murine probe V8.1 in genomic DNA samples digested with the restriction endonucleases Hind III and Bam HI. Use of these RFLP to mark the V beta gene complex allowed complete haplotype assignment in four of seven families studied and provided support for linkage of the V gene complex to the constant region genes. Different combinations of the C and two V region markers can result in eight possible distinct haplotypes. The observation of all but one of the eight possible haplotypes in parents of the families studied suggests that recombination events occur between the C and V region and among members of the V region subfamily marked by the V8.1 probe. These markers can be used for mapping studies of the V beta gene complex in man and will allow an appraisal of possible associations between Tcr beta genes and disease susceptibility. PMID- 2877946 TI - Restriction length polymorphism in the variable region of the Tcr locus linked to histocompatibility antigen H-8 on murine chromosome 14. PMID- 2877947 TI - Regulation of production of type 1 pili among urinary tract isolates of Escherichia coli. AB - The piliation and hemagglutination properties of 54 consecutive Escherichia coli isolates from women with recurrent urinary tract infections were studied. Mannose sensitive hemagglutination (MSHA) of guinea pig erythrocytes, characteristic of type 1-piliated bacteria, was produced by 75% of the isolates, 32% produced mannose-insensitive hemagglutination, and 14% produced no hemagglutination reaction. The production of type 1 pili was examined in those strains that produced MSHA only. Studies with antiserum prepared against purified pili suggested that at least three subtypes of type 1 hemagglutinins were represented among the isolates. All of the type 1-piliated isolates produced MSHA after serial subculture in static broth. After growth on agar, selected type 1-piliated isolates were subdivided into two groups. Many strains apparently suppressed piliation during growth on agar (regulated variants); all colonies became MSHA negative and were composed of nonpiliated cells as shown by electron microscopy. The loss of the MSHA phenotype often occurred after a single overnight passage on agar, and any remaining hemagglutinin was gradually lost with one to three additional passages. Seven strains, however, retained a significant hemagglutination titer after multiple subcultures on agar, and they produced colonies consisting of a mixed population of piliated and nonpiliated cells. These strains were apparently able to oscillate between states of pilus expression and nonexpression during growth on agar (random phase variants). When nonpiliated cells isolated from the mixed, random variant population were plated on agar, they gave rise to hemagglutination-positive colonies that consisted of both piliated and nonpiliated cells. The distinction between random variants and regulated variants was also observed in shaking broth cultures inoculated with nonpiliated cells. The random variants produced MSHA-positive cultures composed of piliated and nonpiliated cells, whereas the regulated strains remained nonpiliated. The results indicate that type 1 pili are a predominant adhesin of uropathogenic E. coli and that during growth on agar only about one-fourth of the type 1-piliated isolates regulate pilus expression by random phase variation. PMID- 2877949 TI - Purification and characterization of Clostridium perfringens iota toxin: dependence on two nonlinked proteins for biological activity. AB - Clostridium perfringens type E iota toxin, a dermonecrotic and lethal binary toxin, was purified to homogeneity. Each protein component of the toxin, iota a (ia) or iota b (ib), appeared as a single band by gradient or sodium dodecyl sulfate-polyacrylamide gel electrophoresis and yielded a single immunoprecipitin arc by crossed immunoelectrophoresis with homologous antiserum. Individually, ia (Mr 47,500) or ib (Mr 71,500) had little biological activity. However, when combined in equimolar amounts, there was a 64-fold increase in the guinea pig dermonecrotic titer. The biological activity of ia was heat stable (85 degrees C for 15 min), whereas ib was inactivated at 55 degrees C. Our results demonstrated that C. perfringens iota toxin required two different, nonlinked protein components for biological activity. PMID- 2877948 TI - Analysis of the genetic determinants coding for the S-fimbrial adhesin (sfa) in different Escherichia coli strains causing meningitis or urinary tract infections. AB - Recently we have described the molecular cloning of the genetic determinant coding for the S-fimbrial adhesin (Sfa), a sialic acid-recognizing pilus frequently found among extraintestinal Escherichia coli isolates. Fimbriae from the resulting Sfa+ E. coli K-12 clone were isolated, and an Sfa-specific antiserum was prepared. Western blots indicate that S fimbriae isolated from different uropathogenic and meningitis-associated E. coli strains, including O83:K1 isolates, were serologically related. The Sfa-specific antibodies did not cross-react with P fimbriae, but did cross-react with F1C fimbriae. Furthermore the sfa+ recombinant DNAs and some cloned sfa-flanking regions were used as probes in Southern experiments. Chromosomal DNAs isolated from O18:K1 and O83:K1 meningitis strains with and without S fimbriae and from uropathogenic O6:K+ strains were hybridized against these sfa-specific probes. Only one copy of the sfa determinant was identified on the chromosome of these strains. No sfa specific sequences were observed on the chromosome of E. coli K-12 strains and an O7:K1 isolate. With the exception of small alterations in the sfa-coding region the genetic determinants for S fimbriae were identical in uropathogenic O6:K+ and meningitis O18:K1 and O83:K1 strains. The sfa determinant was also detected on the chromosome of K1 isolates with an Sfa-negative phenotype, and specific cross hybridization signals were visible after blotting against F1C-specific DNA. In addition homology among the different strains was observed in the sfa-flanking regions. PMID- 2877950 TI - Contribution of cloned virulence factors from uropathogenic Escherichia coli strains to nephropathogenicity in an experimental rat pyelonephritis model. AB - Escherichia coli 536 (O6:K15:H31), which was isolated from a case of urinary tract infection, determines high nephropathogenicity in a rat pyelonephritis system as measured by renal bacterial counts 7 days after infection. The loss of S fimbrial adhesin formation (Sfa-) (mannose-resistant hemagglutination [Mrh-] and fimbria production [Fim-]), serum resistance (Sre-), and hemolysin production (Hly-) in the mutant 536-21 led to a dramatic reduction of bacterial counts from almost 10(5) to only 40 cells per g of kidney. The reintroduction of the cloned S fimbrial adhesin determinant (sfa) increases the virulence of the avirulent mutant strain by a factor of 20; almost the same effect was observed after restoration of serum resistance by integration of an sfa+ recombinant cosmid into the chromosome. Additional reintroduction of the Hly+ phenotype by transformation of two hly determinants increased the virulence of the strains. Hemolysin production determined increased renal elimination of leukocytes and erythrocytes. Thus all three determinants investigated, S fimbriae, serum resistance, and hemolysin, contribute to the multifactorial phenomenon of E. coli nephropathogenicity. PMID- 2877952 TI - Piracy of adhesins: attachment of superinfecting pathogens to respiratory cilia by secreted adhesins of Bordetella pertussis. AB - Two proteins secreted by Bordetella pertussis are known to mediate adherence of these bacteria to mammalian respiratory cilia. When either ciliated cells or other pathogenic bacteria were pretreated with these adhesins, Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus acquired the ability to adhere to cilia in vitro and in vivo. Such piracy of adhesins may contribute to superinfection in mucosal diseases such as whooping cough. PMID- 2877951 TI - Changes in isoenzyme patterns of a cloned culture of nonpathogenic Entamoeba histolytica during axenization. AB - The axenization of an Entamoeba histolytica isolate with a nonpathogenic isoenzyme electrophoretic pattern (zymodeme) was recently achieved for the first time (15). Forty days after the cells were transferred to the medium used for axenic cultivation, the amebae developed virulence properties, and the zymodeme converted to a pathogenic pattern. To exclude the possibility that the original isolate consisted of two zymodeme populations and that conditions of growth selected for a particular population, the experiment was repeated with a cloned culture of a nonpathogenic (zymodeme III) strain, E. histolytica SAW 1734R clAR, isolated by and obtained from P. G. Sargeaunt. Axenization was accomplished, as before, by transferring trophozoites to TYI-S-33 medium containing a mixture of antibiotics to suppress the growth of the associated bacterial flora and a nutritional supplement consisting of gamma-irradiated bacteria. A change in the hexokinase and phosphoglucomutase isoenzyme pattern was observed 21 days after the amebae had been transferred to the axenic medium but before complete axenization of the amebae had occurred. The change in zymodeme was accompanied by an increase in virulence, as evidenced by the ability of fewer amebae to induce hepatic abscesses in hamsters. A reverse conversion to a nonpathogenic zymodeme was also accomplished by reassociating and subculturing the newly converted pathogenic trophozoites of strain SAW 1734R clAR with the bacterial flora that accompanied this ameba in the original xenic culture. The electromobilities of the hexokinase isoenzymes changed back to their original pattern 7 days after the amebae were returned to xenic growth conditions. Our in vitro results demonstrate that culture conditions and bacterial flora can cause changes in the zymodeme and virulence of a cloned ameba isolate and raise the concern that this could happen also in vivo. Thus, the finding of a particular zymodeme in a culture of E. histolytica isolated from a carrier should not be used to predict a clinical condition or serve as a basis for the recommendation of therapy. PMID- 2877953 TI - Dihydroergotamine therapy in orthostatic hypotension due to psychotropic drugs. AB - A double-blind, placebo controlled study with 10 mg per day dihydroergotamine in patients with orthostatic hypotension induced by treatment with psychotropic drugs showed a significant effect in preventing immediate drop in blood pressure after standing up. Preventing an abrupt drop in blood pressure with change of posture hinders symptoms of dizziness and faintness and helps activating patients who otherwise prefer to stay in bed. PMID- 2877954 TI - Pharmacokinetics of tiadipone: a new anxiolytic. AB - In this study 10 healthy volunteers received a single oral dose of 25 mg of tiadipone in coated tablets. The levels of drug in plasma sample of each of the healthy volunteers were determined by a reverse phase HPLC technique. The evolution of the plasma levels of tiadipone with time after oral administration follows a single compartment open kinetic model. The absorption process showed wide interindividual differences with a mean value for the lag time of 0.76 +/- 0.28 h. Tiadipone reaches a maximum plasma concentration with a mean value of 386 ng/ml (range 338-498) between 1 and 3 h after administration. The elimination phase of the drug was seen to be monoexponential. The elimination half-life has a mean value of 3.34 +/- 1.16 h, lower than that established for other benzodiazepines in clinical practice. PMID- 2877955 TI - Duration of oral procaterol protection from methacholine-induced bronchial obstruction. AB - The duration of action of procaterol, a beta-2-adrenoceptor agonist with an entirely new chemical structure, was assessed, in comparison to that of salbutamol, by inhalation of 43 inhalation units of methacholine at time intervals of 1, 3, 5, 7, and 9 hours after intake of the drugs. Procaterol and salbutamol were given in a double-blind random fashion, on different days, to 12 asthmatic children; pulmonary function tests (FVC, FEV1, MEF50, MEF25), skeletal muscle tremor, and vital signs (heart rate and blood pressure) were measured. Although there was no statistical significant difference between procaterol and salbutamol, protection of large and medium airways lasted for about five hours, while normal small airway patency was still present at seven hours. It is concluded that procaterol can be a good alternative beta-2-adrenoceptor agonist when the oral route is needed. PMID- 2877958 TI - Modulation of non-specific bronchial reactivity. AB - There are several drugs that can modify non-specific reactivity induced by various stimuli. Disodium cromoglycate (DSCG) is able to reduce bronchial hyperreactivity status, but its mechanism has not yet been demonstrated. It would be expected to exert its activity either by mastocyte stabilization or by other actions that are not related to mastocyte mediator release. It has been suggested that DSCG has a calcium channel blocking activity. Its possible role as a calcium antagonist suggest a general modifying effect of calcium antagonists against hyperreactivity, although their use in therapy cannot be foreseen. In exercise induced bronchospasm, numerous beta 2-adrenergic drugs have proved more effective than other drugs studied in several investigations. It is unknown whether their effects are to be attributed to a bronchodilator activity or to another mechanism of action. Anticholinergic drugs have a lower protective effect against several stimuli. Theophylline has protective action on histamine bronchospasm which is dependent on the blood levels of theophylline attained. Many drugs currently available can modify bronchial hyperreactivity, but only in a transient way. Several anti-asthmatic drugs cause a decrease of the bronchial hyperreactivity, reducing the release of inflammatory mediators and inhibiting reflex bronchoconstriction. However, at present there are no specific drugs which are able to modify bronchial hyperreactivity with a direct action. PMID- 2877956 TI - Liver function in moderate obesity--study in 534 moderately obese subjects among 4613 male company employees. AB - The influence of moderate obesity on the liver was assessed in 4613 male company employees including 534 moderately obese subjects (30-50 percent overweight). Serum levels of transaminases and gammaglutamyl transferase activities were significantly higher in moderately obese male non-drinkers than in non-obese non drinkers. Twenty-four percent of male non-drinkers with moderate obesity had abnormal levels of sGPT and 47 percent of moderately obese male non-drinkers had significant hepatic steatosis as assessed by computed tomography. Although most previous studies on this subject were concerned with morbid obesity accompanying only those of more than 50 percent overweight or those who required surgery, the results of this study clearly indicate that moderately obese subjects also have frequent liver dysfunction. PMID- 2877957 TI - Thy 1.2 antigen inducing capacity of a calf thymus acid hydrolysate and its fractions. AB - Splenic null cells of normal mice have been shown to undergo phenotypic induction of Thy 1.2 antigen by various thymic extracts. This experimental model has been employed in characterizing the Thy 1.2 inducing ability of an acid lysate from calf thymus and its various fractions. Incubation of splenocytes from C3H/He mice with unfractionated Thymomodulin induces a dose-response percent increase in the Thy 1.2 antigen bearing cells (9.28 +/- 2.6%, p less than 0.05). Comparable increase appears in fractions 5B (9.46 +/- 0.55%, p less than 0.001) and 5C (8.09 +/- 3%, p less than 0.005), obtained by ultrafiltration and containing peptides of m.w. 600-10,000 d and less than 600 d, respectively. The activity is confined to the acid fraction (6.61 +/- 0.54%, p less than 0.001) isolated by isoelectrofocusing. Control lysate from pig duodenal mucosa was devoid of Thy 1.2 inducing activity. The present findings indicate that Thymomodulin possesses Thy 1.2 inducing capacity on murine null cells and that such activity is maintained and enhanced after various fractionation procedures. PMID- 2877959 TI - Coralline hydroxyapatite bone-graft substitutes in a canine metaphyseal defect model. Radiographic-histometric correlation. AB - Radiographic and histometric evaluation of a new form of bone-graft substitute derived from reef-building sea coral was performed in a canine metaphyseal defect model. Blocks of this material were implanted into the proximal tibial metaphyses of eight dogs, with radiographic densitometry and harvesting performed at two, four, six, and 12 months. Histometric analysis demonstrated progressive apposition of host compact bone at the margins and trabecular bone at the interior of the implants with time following surgery. Corrected transmission density determinations correlated significantly with degree of osseous ingrowth (R = -0.78), void volume fraction (R = 0.88), and postoperative interval (R = 0.88). These results support the successful early application of coralline hydroxyapatite bone-graft substitutes as an alternative to autogenous grafting in the clinical setting, and indicate that the course of incorporation into host bone can be noninvasively monitored using densitometric techniques. PMID- 2877961 TI - Smoking in public places. PMID- 2877960 TI - Chromogranin A (CGA) in the gastro-entero-pancreatic (GEP) endocrine system. I. CGA in the mammalian endocrine pancreas. AB - Chromogranin A (CGA), a protein at first detected in the adrenal medulla, has recently been found also in other organs, e.g. the endocrine pancreas. However, immunohistochemical findings concerning the cellular source of pancreatic CGA were controversial. Therefore, the endocrine pancreas of 10 mammalian species (man, tupaia, mole, cat, dog, pig, guinea pig, rabbit, rat) was investigated immunohistochemically for CGA-like immunoreactivities on serial semithin plastic sections using a high-titer polyclonal antiserum against bovine CGA. The results show that basically all pancreatic endocrine cell types are CGA-immunoreactive; however, every species has its own pattern of CGA-immunoreactive cell types. Other findings of the present studies indicate that the physiological function of CGA in pancreatic endocrine cells is related to the storage mechanisms of peptide hormones. Finally, a methodological approach is given to obtain not only qualitative but also semi-quantitative data during immunohistochemical investigations. PMID- 2877962 TI - Oral transmission of human T-cell leukemia virus type I in the rabbit. AB - Four female rabbits were given twice-weekly oral inoculation of 2-4 X 10(7) cells from a male rabbit lymphoid cell line persistently infected with human T-cell leukemia virus type I (HTLV-I). After 8 weeks, one of them was found to be seroconverted for HTLV-I. Peripheral lymphocytes from the 4 rabbits were cultured in the presence of T-cell growth factor, and a lymphoid cell line with a normal female karyotype was established only from the seroconverted rabbit. This cell line was reactive with a monoclonal antibody to rabbit T-cells and expressed HTLV I antigens and virus particles. PMID- 2877964 TI - Dose-response curves of central and peripheral airways to nicotine injections in dogs. AB - The dose-response curves of the central and peripheral airways to intravenously injected nicotine were studied in 55 anesthetized dogs. With intact vagi, nicotine caused a dose-dependent increase in central airway resistance (Rc) similar to the increase in peripheral airway resistance (Rp) at concentrations ranging from 4 to 64 micrograms/kg. However, the responses of both Rc and Rp fell progressively when sequential doses of nicotine greater than 256 micrograms/kg were administered. With intact vagi and the administration of propranolol, there was a greater increase in Rp than in Rc at a nicotine dose of 64 micrograms/kg (P less than 0.05). With vagotomy, the responsiveness of both central and peripheral airways to nicotine decreased with doses of nicotine less than 64 micrograms/kg, but with doses of nicotine greater than 256 micrograms/kg the suppressive effect of nicotine on both Rc and Rp was less than that seen with intact vagi. Under conditions in which the vagi were cut and atropine administered, the responsiveness of nicotine was even further depressed. Combinations either of atropine and chlorpheniramine or atropine and phenoxybenzamine also completely blocked reactions to nicotine. Additionally reactions to nicotine were completely blocked by hexamethonium. These results suggest that nicotine increases both Rc and Rp mainly through a vagal reflex and stimulation of the parasympathetic ganglia. PMID- 2877963 TI - Prevention of HTLV-I transmission through the breast milk by a freeze-thawing process. AB - Fifteen human breast milk samples obtained from mothers seropositive for human T cell lymphotropic virus type-I (HTLV-I) antigen were kept frozen overnight at -20 degrees. Each milk sample was then co-cultivated with cord lymphocytes obtained from 15 anti-HTLV-I antibody-negative mothers. No HTLV-I antigen-positive cells were detected among the cord lymphocytes subjected to co-cultivation. These results suggest that thawing of frozen breast milk may prevent HTLV-I transmission from mother to child via breast milk. PMID- 2877965 TI - Influence of triamcinolone and somatostatin on morphometric parameters of cultured intestinal mucosa. AB - Mucosal biopsies from rabbit ileum were organ cultured for 24 h. The influence of triamcinolone and somatostatin on villus height and diameter as well as crypt depth and the number of mitoses was measured at various times during 24 h of culture as indices of cell proliferation and tissue maintenance. It could be shown that triamcinolone reduced cell proliferation slightly but preserved mucosal structure in organ culture. Somatostatin inhibited crypt cell proliferation, without any effect on other morphological parameters. PMID- 2877966 TI - Secondary attachment site for bacteriophage lambda in the guaB gene of Escherichia coli. AB - lambda gua transducing bacteriophages were used to identify and sequence the secondary attachment site for lambda in the guaB gene of Escherichia coli. The sequence matched the primary core sequence at nine positions, and a putative integrase binding-site overlapped the left core-arm junction. Recombinational crossover occurred between nucleotides -3 and +2 of the core region. PMID- 2877968 TI - Effect of glutamine on growth and heterocyst differentiation in the cyanobacterium Anabaena variabilis. AB - Mutants of the cyanobacterium Anabaena variabilis that were capable of increased uptake of glutamine, as compared with that in the parental strains, were isolated. Growth of these mutants and their parental strains was measured in media containing N2, ammonia, or glutamine as a source of nitrogen. All strains grew well with any one of these sources of fixed nitrogen. Much of the glutamine taken up by the cells was converted to glutamate. The concentrations of glutamine, glutamate, arginine, ornithine, and citrulline in free amino acid pools in glutamine-grown cells were high compared with the concentrations of these amino acids in ammonia-grown or N2-grown cells. All strains capable of heterocyst differentiation, including a strain which produced nonfunctional heterocysts, grew and formed heterocysts in the presence of glutamine. However, nitrogenase activity was repressed in glutamine-grown cells. Glutamine may not be the molecule directly responsible for repression of the differentiation of heterocysts. PMID- 2877967 TI - Expression of pili from Bacteroides nodosus in Pseudomonas aeruginosa. AB - The pili of Bacteroides nodosus, the causative agent of ovine footrot, constitute the major host-protective immunogen against homologous serotypic challenge. The pilin gene from B. nodosus 198 has been cloned and morphologically expressed as extracellular pili in Pseudomonas aeruginosa by using a plasmid-borne, thermoregulated expression system. B. nodosus pilin could not be detected in cultures of P. aeruginosa grown at 32 degrees C, but after induction at 37 degrees C, B. nodosus pili were expressed on the cell surface of P. aeruginosa to the virtual exclusion of the host cell pili. Pili harvested from induced P. aeruginosa cultures were used to immunize sheep against footrot. The serum agglutinating antibody titers of vaccinated sheep were comparable to those of sheep receiving pili from B. nodosus. Subsequent challenge of the sheep with B. nodosus 198 indicated that the recombinant- DNA-derived pili vaccine and the B. nodosus pili vaccine provided similar levels of protection against footrot. PMID- 2877969 TI - Expression of alpha-amylase in Bacillus licheniformis. AB - In Bacillus licheniformis, alpha-amylase production varied more than 100-fold depending on the presence or absence of a catabolite-repressing carbon source in the growth medium. alpha-Amylase was produced during the growth phase and not at the onset of the stationary phase. Induction of alpha-amylase correlated with synthesis of mRNA initiating at the promoter of the alpha-amylase gene. PMID- 2877970 TI - Nucleotide sequence of the tra YALE region from IncFV plasmid pED208. AB - The pED208 plasmid is a 90-kilobase conjugative plasmid which is the derepressed form of Fo lac plasmid (IncFV). A 3.3-kilobase HindIII-PstI fragment from the pED208 plasmid was cloned and sequenced and was found to contain four open reading frames which were highly homologous to the traA, traL, traE, and traY gene products of the F plasmid. The pED208 traA propilin protein was 119 amino acids in length, consisting of a leader sequence of 55 amino acids and a mature pilin subunit of 64 residues. The leader sequence contained a hydrophobic region followed by a classic signal peptidase cleavage site (Ala-Ser-Ala-55). F and pED208 pilin proteins shared 27 conserved residues and had similar predicted secondary structures. The pED208 traA and traL genes were separated by a single base pair, and no ribosome binding site preceded the traL gene. The pED208 traY gene contained an IS2 insertion element in orientation II 180 nucleotides (60 residues) upstream of the traY stop codon. This insertion of IS2 resulted in a predicted fusion peptide of 69 residues for traY which may provide the observed traY activity. Since IS2 is absent in the wild-type plasmid, Fo lac, derepression and concomitant multipiliation may be due to the insertion of IS2 providing constitutive expression of the pED208 tra operon. PMID- 2877971 TI - Characterization of a bacteriocinogenic plasmid from Clostridium perfringens and molecular genetic analysis of the bacteriocin-encoding gene. AB - The bacteriocinogenic plasmid pIP404 from Clostridium perfringens was isolated and cloned in Escherichia coli, and its physical map was deduced. Expression of the bcn gene, encoding bacteriocin BCN5, is inducible by UV irradiation of C. perfringens and thus resembles the SOS-regulated bacteriocin genes of enteric bacteria. The location of bcn on pIP404 was established by a dot-blot procedure, using specific hybridization probes to analyze mRNA samples from induced and uninduced cultures. From the nucleotide sequence of its gene, the molecular weight of BCN5 was deduced to be 96,591, and a protein of this size was secreted by bacteriocin-producing cultures of C. perfringens. The primary structure of the protein suggests that it may function as an ionophore, since a hydrophobic domain, resembling those of the ionophoric colicins, is present at the COOH terminus. No bacteriocin activity could be detected in E. coli harboring plasmids bearing the bcn gene, even when the transcriptional and translational signals were replaced by those of lacZ. A possible explanation may be found in the unusual codon usage of the adenine-thymine-rich bcn gene, as this shows a preference for codons with a high adenine-plus-thymine content, especially in the wobble position. Many of the frequently used codons correspond to those recognized by minor tRNA species in E. coli. Consequently, bcn expression might be limited by tRNA availability in this bacterium. PMID- 2877973 TI - The Saccharomyces cerevisiae start mutant carrying the cdc25 mutation is defective in activation of plasma membrane ATPase by glucose. AB - Activation of plasma membrane ATPase by the addition of glucose was examined in several cell division cycle mutants of Saccharomyces cerevisiae. The start mutant carrying the cdc25 mutation was shown to be defective in ATPase activation at the restrictive temperature. Genetic analysis showed that lack of growth and defective activation of ATPase at the restrictive temperature were caused by the same mutation. It was also found that CDC25 does not map at the same locus as the structural gene of plasma membrane ATPase (PMA1). We conclude that the product of CDC25 controls the activation of ATPase. PMID- 2877972 TI - Identification of two new hemagglutinins of Escherichia coli, N-acetyl-D glucosamine-specific fimbriae and a blood group M-specific agglutinin, by cloning the corresponding genes in Escherichia coli K-12. AB - Genes encoding the Escherichia coli IH11165 hemagglutinins with specificity for terminal N-acetyl-D-glucosamine and blood group M antigen, respectively, were cloned by a cosmid cloning procedure. A 22-kilobase-pair subclone expressed both hemagglutination specificities in the nonhemagglutinating E. coli HB101 recipient strain. Derivatives obtained by insertion and deletion mutagenesis expressed either one of the two hemagglutination specificities. Both agglutinins were purified; the agglutinin recognizing terminal N-acetyl-D-glucosamine was associated with a new type of fimbria (G fimbria) with an apparent subunit molecular mass of 19.5 kilodaltons, whereas the blood group M agglutinin (M agglutinin) was nonfimbrial and had an apparent subunit mass of 21 kilodaltons. PMID- 2877974 TI - gamma-Glutamyltranspeptidase from Escherichia coli K-12: purification and properties. AB - gamma-Glutamyltranspeptidase (GGT) (EC 2.3.2.2) was purified from the periplasmic fraction of Escherichia coli K-12 to electrophoretic homogeneity. The final purification step, chromatofocusing, gave two protein peaks showing GGT activity (fractions A and B). The major heavy fraction (fraction A) consisted of two different subunits, with molecular weights of 39,200 and 22,000. The minor light fraction (fraction B) consisted of those with molecular weights of 38,600 and 22,000. Fraction A catalyzes the hydrolysis and transpeptidation of all gamma glutamyl compounds tested, but it prefers basic amino acids and aromatic amino acids as acceptors. The apparent Km values for glutathione and gamma-glutamyl-p nitroanilide as gamma-glutamyl donors in the transpeptidation reaction were both 35 microM, and those for glycylglycine and L-arginine as acceptors were 0.59 and 0.21 M, respectively. The enzyme was inhibited by some amino acids and by protease inhibitors and affinity-labeling reagents for GGT. The temperature stability of the purified GGT supports our hypothesis that E. coli GGT is synthesized only at lower temperature rather than that the synthesized GGT is degraded or inactivated at higher temperature. PMID- 2877975 TI - gamma-Glutamyltranspeptidase from Escherichia coli K-12: formation and localization. AB - Escherichia coli cells showed maximum activity of gamma-glutamyltranspeptidase (EC 2.3.2.2) when they were grown at 20 degrees C, 14% of maximum activity at 37 degrees C, and none at 43 degrees C. The enzyme activity of intact cells grown at 20 degrees C was stably maintained after the temperature was changed to 45 degrees C. The activity increased during the exponential phase, and maximum activity was found at stationary phase. Its intracellular localization in the periplasmic space was confirmed. PMID- 2877976 TI - Mania in adolescence. AB - The clinical features, treatment, and outcome of bipolar disorder in a consecutive series of 14 adolescent patients are described. Diagnostic confusion was common, although the clinical features were similar to those found in adult patients. Treatment response and short-term outcome seemed favorable. The findings are discussed in the light of current literature. PMID- 2877977 TI - Neuroleptic dose and the need for prophylactic anticholinergic drugs. PMID- 2877978 TI - Developmental changes of gamma-aminobutyric acid (GABA) and putative amino acid neurotransmitters in the organotypic culture of newborn mouse cerebellum. AB - The quantitative changes and metabolism of GABA and putative amino acid neurotransmitters during early developmental stages in the organotypic culture of newborn mouse cerebellum were examined by using the high-performance liquid chromatograph (HPLC) technique. D-[U-14C]Glucose was used as a precursor of amino acids. To analyze amino acid neurotransmitters, explants were incubated for 4 weeks under standard conditions. The amount of GABA linearly increased from 8.7 +/- 1.3 nmol/mg protein (2 days in vitro, 2 DIV) to 26.5 +/- 6.1 nmol/mg protein (15 DIV) and was saturated after that (24.0 +/- 3.6 nmol/mg protein at 30 DIV). During the period of GABA increase, the capability for GABA synthesis from [14C]glucose increased rapidly from 3.03 +/- 0.67 nCi/mg protein (2 DIV, 3 h incubation) to 9.32 +/- 1.34 nCi/mg protein (15 DIV, 3 h incubation). In the case of glutamic acid, a putative neurotransmitter of granule cell parallel fibers in the cerebellum, the amount in explants was nearly constant during incubation, in contrast with the fact that the amount in vivo gradually increased. However, the capability for glutamic acid synthesis from [14C]glucose increased from 10.80 +/- 3.01 nCi/mg protein (2 DIV, 1 h incubation) to 27.62 +/- 4.71 nCi/mg protein (22 DIV, 1 h incubation). In the case of taurine, found in abundance in fetal brain and supposed to play a specific role in the development and maturation of the central nervous system, the amount in explants decreased from 139.8 +/- 4.0 nmol/mg protein (2 DIV) to 54.0 +/- 0.8 nmol/mg protein (30 DIV).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2877979 TI - ADP binding to TF1 and its subunits induces ultraviolet spectral changes. AB - Adenine nucleotide binding sites on the coupling factor ATPase of thermophilic bacterium PS3 (TF1) were investigated by UV spectroscopy and by equilibrium dialysis. When ADP was mixed with TF1 in the presence and in the absence of Mg2+, an UV absorbance change was induced (t1/2 approximately 1 min) with a peak at about 278 nm and a trough at about 250 nm. Similar spectral changes were induced by ADP with the isolated beta subunits in the presence and in the absence of Mg2+, and with the isolated alpha subunits in the presence of Mg2+ although the magnitudes of the changes were different. From equilibrium dialysis measurement we identified two classes of nucleotide binding sites in TF1 in the presence of Mg2+, three high-affinity sites (Kd = 61 nM) and three low-affinity sites (Kd = 87 microM). In the absence of Mg2+, TF1 has one high-affinity site (Kd less than 10 nM) and five low-affinity sites (Kd = 100 microM). Moreover, we found a single Mg2+-dependent ADP binding site on the isolated alpha subunit and a single Mg2+ independent ADP binding site on the isolated beta subunit. From the above observations, we concluded that the three Mg2+-dependent high-affinity sites for ADP are located on the alpha subunit in TF1 and that the single high-affinity site is located on one of the beta subunits in TF1 in the absence of Mg2+. PMID- 2877980 TI - Regulation of carbamoyl phosphate synthetase-aspartate transcarbamoylase dihydroorotase gene expression in growing and arrested cells. AB - We have studied expression of the carbamoyl-P synthetase-aspartate transcarbamoylase-dihydroorotase (CAD) gene in growing or confluent Syrian hamster cells, and also in cells arrested by depriving them of serum or restimulated by adding fresh serum. In contrast to other biosynthetic enzymes such as dihydrofolate reductase, the amount of the CAD enzyme decreased very little when growth was arrested, as judged by the small change in aspartate transcarbamoylase activity. However, the level of CAD mRNA was about 10-fold lower in arrested cells than in growing cells. The rate of transcription of CAD, measured by the nuclear run-off technique, decreased roughly in parallel with the decrease in the steady-state level of the mRNA, suggesting that control of transcription is probably an important element in the overall regulation of CAD gene expression. Expression of a different gene which lies near the 5' end of CAD changed in parallel with that of CAD, but expression of two other genes in the same region was insensitive to the growth state of the cells. Therefore, control of gene expression as a function of growth was specific rather than a reflection of more general changes in chromatin structure in the vicinity of CAD. PMID- 2877981 TI - Cross-linking site in fibrinogen for alpha 2-plasmin inhibitor. AB - A plasma proteinase inhibitor, alpha 2-plasmin inhibitor (alpha 2PI), is cross linked with alpha chain of fibrin(ogen) by activated coagulation Factor XIII (plasma transglutaminase). alpha 2PI serves only as a glutamine substrate (amine acceptor) for activated Factor XIII in the cross-linking reaction, and the cross linking occurs between Gln-2 of the alpha 2PI molecule and a lysine residue (amine donor) of fibrin(ogen) alpha chain, whose position was investigated. alpha 2PI and fibrinogen were reacted by activated Factor XIII. The resulting alpha 2PI fibrinogen A alpha chain complex was separated and subjected to two cycles of Edman degradation using phenyl isothiocyanate for the first cycle and dimethylaminoazobenzene-isothiocyanate for the second cycle. The aqueous phase after the cleavage stage of the second cycle, containing dimethylaminoazobenzene thiohydantoin-Gln cross-linked with A alpha chain, was subjected to CNBr fragmentation and tryptic digestion. Only one of the peptides was found to have the peak of absorbance at 420 nm, indicating the presence of dimethylaminoazobenzene-thiohydantoin-Gln in that peptide. The peptide was identified as corresponding to residues Asn-290-Arg-348 of A alpha chain by analyses of the NH2-terminal amino acid sequence and amino acid composition. The peptide contains a single lysine at position 303, indicating that Lys-303 of fibrinogen A alpha chain is the lysine residue that forms a cross-link with Gln-2 of alpha 2PI. PMID- 2877982 TI - Covalent coupling of a resact analogue to guanylate cyclase. AB - GGGYG-resact (Gly-Gly-Gly-Tyr-Gly-Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly Arg -Leu-NH2) was synthesized and shown to possess the same respiration stimulating activity and receptor-binding ability as resact. The incubation of intact sperm cells with radioiodinated peptide, 125I-GGGYG-resact, and the chemical cross-linking reagent, disuccinimidyl suberate, resulted in the appearance of a single, major radioactive band of apparent molecular weight 160,000 (sodium dodecyl sulfate-polyacrylamide gel electrophoresis). The interaction was specific since 150 nM nonradioactive resact but not speract (200 nM) blocked formation of the radioactive band. The radioactive, cross-linked protein co-migrated with 32P-labeled guanylate cyclase and could be immunoprecipitated with a polyclonal antibody raised in rabbits against the sperm guanylate cyclase. The incubation of intact cells with NH4Cl resulted in the partial dephosphorylation of guanylate cyclase and a change in its apparent molecular weight from 160,000 to 150,000; NH4Cl also caused the same conversion in the apparent molecular weight of the cross-linked protein. These data demonstrate that an analogue of resact can be covalently coupled to guanylate cyclase with the specificity predicted for the peptide receptor. PMID- 2877983 TI - Gentamicin nucleotidyltransferase. Stereochemical inversion at phosphorus in enzymatic 2'-deoxyadenylyl transfer to tobramycin. AB - Gentamicin nucleotidyltransferase-catalyzed reaction of (Sp)-[alpha-17O]dATP with tobramycin produced 2"-(2'-deoxyadenosine 5'-[17O]phosphoryl)tobramycin. The configuration at phosphorus in this product was shown to be Rp by chemical degradation to chiral [17O, 18O]dAMP using a stereochemically defined procedure, and determination of the configuration at phosphorus in this product. Periodate base treatment of 2"-(2'-deoxyadenosine 5'-[17O]phosphoryl)tobramycin followed by NaBH4 reduction produced (2-glyceryl)-[17O]dAMP, which upon snake venom phosphodiesterase-catalyzed hydrolysis in H(2)18O produced [17O,18O] dAMP. The configuration at phosphorus in this product was shown to be S by enzymatic phosphorylation to [17O,18O]dATP, adenylylcyclase (Bordetella pertussis) catalyzed cyclization to 3',5'-cyclic [17O,18O]dAMP, and 31P NMR analysis of the ethyl esters. Since snake venom phosphodiesterase-catalyzed hydrolyses proceed with retention of configuration at phosphorus, (Sp)-[17O,18O]dAMP must have been produced from (Rp)-(2-glyceryl)-[17O]dAMP; and since the chemical degradation to the latter compound did not involve cleavage of any bonds to phosphorus, the initial enzymatic product must have been (Rp)-2"-(2'-deoxyadenosine 5' [17O]phosphoryl)tobramycin. Therefore, nucleotidyl transfer catalyzed by gentamicin nucleotidyl-transferase proceeds with inversion of configuration at phosphorus, and the reaction mechanism involves an uneven number of phosphotransfer steps. Inasmuch as this is an uncomplicated two-substrate group transfer reaction, the mechanism probably involves direct nucleotidyl transfer from the nucleoside triphosphate to the aminoglycoside. The B. pertussis adenylylcyclase reaction was shown to proceed with inversion at phosphorus, as has been established for other adenylylcyclases. PMID- 2877984 TI - Regulation of rat liver 3-hydroxy-3-methylglutaryl coenzyme A synthase and the chromosomal localization of the human gene. AB - 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase was purified to homogeneity from rat liver cytoplasm. The active enzyme is a dimer composed of identical subunits of Mr = 53,000. The amino acid composition and the NH2 terminal sequence are presented. Partial cDNA clones for the enzyme were isolated by screening of a rat liver lambda gt11 expression library with antibodies raised against the purified protein. The identity of the clones was confirmed by hybrid selection and translation. When rats were fed diets supplemented with cholesterol, cholestyramine, or cholestyramine plus mevinolin, the hepatic protein mass of cytoplasmic synthase, as determined by immunoblotting, was 25, 160, and 1100%, respectively, of the mass observed in rats fed normal chow. Comparable changes in enzyme activity were observed. Approximately 9-fold increases in both HMG-CoA synthase mRNA mass and synthase mRNA activity were observed when control diets were supplemented with cholestyramine and mevinolin. When rats were fed these two drugs and then given mevalonolactone by stomach intubation, there was a 5-fold decrease of synthase mRNA within 3 h. These results indicate that cytoplasmic synthase regulation occurs primarily at the level of mRNA. This regulation is rapid and coordinate with that observed for HMG CoA reductase. The chromosomal localization of human HMG-CoA synthase was determined by examining a panel of human-mouse somatic cell hybrids with the rat cDNA probe. Interestingly, the synthase gene resides on human chromosome 5, which has previously been shown to contain the gene for HMG-CoA reductase. Regional mapping, performed by examination of a series of chromosome 5 deletion mutants and by in situ hybridization to human chromosomes indicates that the two genes are not tightly clustered. PMID- 2877986 TI - Bordetella pertussis adenylate cyclase. Purification, characterization, and radioimmunoassay. AB - The extracellular adenylate cyclase of Bordetella pertussis was purified either as a free enzyme or as a complex with calmodulin. The purified enzyme has a specific activity of 1600 mumol of cAMP min-1 X mg-1 and exists under two molecular forms of 45 and 43 kDa which are apparently structurally related. Calmodulin increased considerably the resistance of adenylate cyclase to inactivation by trypsin. Although trypsin cleaved the adenylate cyclase calmodulin complex, the digested fragments remained associated by noncovalent interactions in an active conformation. Specific mouse anti-adenylate cyclase antibodies inhibit adenylate cyclase activity and were used to develop a specific radioimmunoassay that allows detection of as little as 5 ng of adenylate cyclase in culture supernatants. PMID- 2877985 TI - Somatostatin is targeted to the regulated secretory pathway of gonadotrophs in transgenic mice expressing a metallothionein-somatostatin gene. AB - The pituitaries of transgenic mice that express a metallothionein-somatostatin fusion gene contain high concentrations of somatostatin-14 exclusively in the gonadotrophic cells. The purpose of this study was to determine whether somatostatin expressed from the foreign fusion gene enters the normal secretory pathway within these cells. Immuno-gold labeling of serial thin sections localized somatostatin to the secretory granules of gonadotropin-producing cells. The gonadotroph-specific hypophysiotropic factor, luteinizing hormone-releasing hormone caused a dose-dependent secretion of somatostatin when applied to primary pituitary cultures from these mice. Growth hormone-releasing hormone, thyrotropin releasing hormone, corticotropin releasing factor, and dopamine did not affect somatostatin secretion. These experiments demonstrate that a neurosecretory peptide encoded by a foreign gene can enter the regulated secretory pathway of pituitary cells from transgenic mice. PMID- 2877987 TI - Evidence for pyrroloquinolinequinone as the carbonyl cofactor in lysyl oxidase by absorption and resonance Raman spectroscopy. AB - The present study investigated the possibility that pyrroloquinolinequinone (PQQ), an aromatic carbonyl recently indicated to be the carbonyl cofactor in bovine plasma amine oxidase, may also be present at the active site of lysyl oxidase. The absorption and resonance Raman spectra of the phenylhydrazones of bovine plasma amine oxidase, of peptides derived from the active site of bovine aorta lysyl oxidase, and of PQQ were very similar, indicating that the carbonyl cofactor of lysyl oxidase is PQQ or a compound which closely resembles PQQ. PMID- 2877988 TI - beta-Oxidation of polyunsaturated fatty acids by rat liver peroxisomes. A role for 2,4-dienoyl-coenzyme A reductase in peroxisomal beta-oxidation. AB - beta-Oxidation of unsaturated fatty acids was studied with isolated solubilized or nonsolubilized peroxisomes or with perfused liver isolated from rats treated with clofibrate. gamma-Linolenic acid gave the higher rate of beta-oxidation, while arachidonic acid gave the slower rate of beta-oxidation. Other polyunsaturated fatty acids (including docosahexaenoic acid) were oxidized at rates which were similar to, or higher than, that observed with oleic acid. Experiments with 1-14C-labeled polyunsaturated fatty acids demonstrated that these are chain-shortened when incubated with nonsolubilized peroxisomes. Spectrophotometric investigation of solubilized peroxisomal incubations showed that 2,4-dienoyl-CoA esters accumulated during peroxisomal beta-oxidation of fatty acids possessing double bond(s) at even-numbered carbon atoms. beta Oxidation of [1-14C]docosahexaenoic acid by isolated peroxisomes was markedly stimulated by added NADPH or isocitrate. This fatty acid also failed to cause acyl-CoA-dependent NADH generation with conditions of assay which facilitate this using other acyl-CoA esters. These findings suggest that 2,4-dienoyl-CoA reductase participation is essential during peroxisomal beta-oxidation if chain shortening is to proceed beyond a delta 4 double bond. Evidence obtained using arachidionoyl-CoA, [1-14C]arachidonic acid, and [5,6,8,9,11,12,14,15 3H]arachidonic acid suggests that peroxisomal beta-oxidation also can proceed beyond a double bond positioned at an odd-numbered carbon atom. Experiments with isolated perfused livers showed that polyunsaturated fatty acids also in the intact liver are substrates for peroxisomal beta-oxidation, as judged by increased levels of the catalase-H2O2 complex on infusion of polyunsaturated fatty acids. PMID- 2877989 TI - Biologically active, recombinant DNA in clathrin-coated vesicles isolated from rat livers after in vivo injection of liposome-encapsulated DNA. AB - DNA entrapped in liposomes containing lactosylceramide in the bilayers is found to be associated with clathrin-coated vesicles isolated from the rat livers after intravenous injection of these liposomes. The presence of the exogenous DNA in the coated vesicles was detected by Southern blotting. The amount of DNA present in the coated vesicles does not appear to vary up to 4 h after injection of the liposomes into the animals. The recognition of the lactosyl group present in the liposome by the galactose receptor present on the surface of the different liver cells may lead to their internalization in a way analogous to receptor-mediated endocytosis of various macromolecules. DNA present in the lumen of the coated vesicles is found to be biologically active as evidenced by its replication in bacterial cells and mouse fibroblasts. PMID- 2877990 TI - Characterization of covalently cross-linked pancreatic somatostatin receptors. AB - The receptor for somatostatin present in rat pancreatic plasma membranes was characterized by affinity labeling with [125I-Tyr11]somatostatin utilizing three different heterobifunctional cross-linking agents: N-5-azido-2-nitrobenzoyloxy succinimide, N-succinimidyl 6-(4-azido 2'-nitrophenylamine)hexanoate, and N hydroxysuccinimidyl 4-azido-benzoate. Analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography revealed a broad band of Mr = 92,000 when any of the three cross-linkers was used; N-succinimidyl 6-(4 azido 2'-nitrophenylamine), however, was most efficient. Labeling of the Mr = 92,000 protein band was not affected by reducing agents but was sensitive to somatostatin and guanine nucleotides, particularly GTP gamma S, at concentrations which reduced binding to the receptor. The affinity-labeled protein could be solubilized completely with Zwittergent 3-12, partially with Triton X-100 and 3 [(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid, and poorly with Zwittergent 3-08 and digitonin. When exposed to agarose-coupled lectins, the detergent solubilized, labeled Mr = 92,000 protein was completely adsorbed to wheat germ agglutinin, partially to ricin communis II, and not at all to concanavalin A or lotus or lentil lectin. The Mr = 92,000 protein bound to wheat germ agglutinin-agarose was not eluted by N-acetylglucosamine but was by triacetylchitotriose, providing a considerable purification of the somatostatin receptor. These data allow us to conclude that the somatostatin receptor is a monomeric glycoprotein with an Mr = 90,000 binding subunit which probably contains a polymeric arrangement of N-acetylglucosamine residues. PMID- 2877991 TI - Extended X-ray absorption fine structure of Mn2+ and Mn2+ X ATP complex bound to coupling factor 1 of the H+-ATPase from chloroplasts. AB - The spinach chloroplast ATPase, coupling factor 1, contains three tight Mn2+ binding sites which interact cooperatively. The bound manganese coordinations were studied by x-ray absorption fine structure analysis. Mn2+ was found to be bound to the enzyme with an average Mn-O bond length of 2.15 +/- 0.15 A, significantly shorter than the 2.15 +/- 0.15 A of the Mn-O bond of the average first hydration shell for Mn2+ in aqueous solution. On adding ATP to the manganese-enzyme mixture, a tertiary complex of Mn2+ X ATP X enzyme was formed as indicated by the appearance of a second shell. Mn-P bond distances were estimated at 4.95 +/- 0.15 A in the tertiary Mn2+ X ATP X enzyme complex, which was considerably longer than the Mn-P bond distance of 3.36 +/- 0.15 A for the Mn2+ X ATP complex in aqueous solution. The Mn-P bond distance in the tertiary Mn2+ X ATP X enzyme complex decreased to 4.32 +/- 0.15 A when selenite, a potent effector of ATPase activity, was added. Based on these results, it is suggested that the tertiary complex is required for catalysis. The stimulation of ATP hydrolysis by anions such as selenite may be the result of shortening the distance between Mn2+ and the ATP phosphates in the enzyme active site. PMID- 2877992 TI - Interaction of the D-isomer of gamma-methylene glutamate with an active site thiol of gamma-glutamylcysteine synthetase. AB - gamma-Glutamylcysteine synthetase has a thiol group in the vicinity of its glutamate-binding site. During efforts to find a covalently bound inhibitor, interaction of the enzyme with gamma-methylene glutamate was examined because this analog of glutamate, which has an alpha,beta-unsaturated moiety, would be expected to bind at the glutamate site and might react with an active site thiol. gamma-Methylene glutamate, which is not a significant substrate, inhibits the enzyme competitively toward glutamate. Preincubation of the enzyme with gamma methylene DL-glutamate led to substantial inactivation which was dependent upon the presence of Mg2+ or Mn2+; glutamate protected against inactivation. Inactivation was observed with the D-isomer of gamma-methylene glutamate, but not with the corresponding L-isomer. The inactivated enzyme contains close to 1 mol of gamma-methylene glutamate/mol of enzyme. Studies in which enzyme inactivated by treatment with [14C]gamma-methylene glutamate was hydrolyzed indicate that gamma-methylene glutamate reacts with an active site thiol. PMID- 2877993 TI - Compartment syndrome of the foot. A case report. PMID- 2877994 TI - Transferrin receptor polarity and recycling accuracy in "tight" and "leaky" strains of Madin-Darby canine kidney cells. AB - We have characterized the polarity of the transferrin receptor in the epithelial Madin-Darby canine kidney (MDCK) cell line. The receptor is present in approximately 165,000 copies per cell, migrates as a diffuse band upon SDS gel electrophoresis with Mr 90,000, displays a dissociation constant for diferritransferrin at neutral pH of approximately 2 nM, and is active in essentially all of the cells of the population. Transferrin-mediated 55Fe uptake was used to measure the polarity of active transferrin receptors in filter-grown MDCK cells. The ratio of basolateral to apical receptors was approximately 800:1 for the high resistance strain I MDCK cells (typically greater than 2,000 ohm X cm2) and approximately 300:1 for the lower resistance strain II cells (less than 350 ohm X cm2). In combination with morphometric data this shows that a difference in resistance between these two strains is not reflected in a significant difference in cell surface polarity. We used the recycling of transferrin receptor in filter-grown MDCK cells to evaluate the accuracy of the sorting of a basolateral protein during endocytosis. Monitoring the amount of apically released 125I-labeled transferrin after application of 55Fe- and 125I labeled transferrin to the basolateral surface provided a sensitive assay of the accuracy of sorting during recycling of the receptor from endosomes to the plasma membrane. The accuracy of transferrin receptor sorting (greater than 99.88%) during a single cycle of transit between the endosome and the plasma membrane is sufficient to maintain the high level of polarity of the cell. PMID- 2877996 TI - Selective induction of tyrosine hydroxylase by cell-cell contact in bovine adrenal chromaffin cells is mimicked by plasma membranes. AB - As a first step towards the identification and purification of the molecule(s) that are involved in cell contact-mediated tyrosine hydroxylase (TH) induction in cultures of bovine adrenal chromaffin cells, we have prepared plasma membranes (PM) from bovine adrenal medulla and tested their ability to mimick cell contact mediated TH induction in low density chromaffin cultures. PM indeed induced TH in a manner similar to that observed in high density cultures. The maximal TH induction reached by PM corresponded to 69% of that of high density cultures, and half-maximal TH induction was obtained with 12 micrograms of PM per ml of medium. The induction of TH by PM was blocked by alpha-amanitin as observed in high density cultures. Since acetylcholinesterase was neither induced in high density nor in PM-treated low density cultures, an induction of TH as a result of a general increase in protein synthesis was excluded. The cell contact molecule(s) appear to be intrinsic membrane proteins. They were not removed by high or low salt extraction, but solubilized by 50 mM octylglucoside. They were resistant to 0.1% trypsin and heat denaturation but inactivated by 0.01% chymotrypsin. PM isolated from the adrenal cortex, kidney, and liver also induced TH in low density chromaffin cell cultures, although to a smaller extent than PM of the adrenal medulla. In contrast, muscle and erythrocyte PM were inactive. This shows that the cell contact molecule(s) are not restricted to the adrenal medulla, but are also present in some other but not all tissues. PMID- 2877995 TI - Chymotrypsin substrate analogues inhibit endocytosis of insulin and insulin receptors in adipocytes. AB - To explore the possible role of proteolytic step(s) in receptor-mediated endocytosis of insulin, the effects of inhibitors of various classes of proteases on the internalization process were studied in isolated rat adipocytes. Intracellular accumulation of receptor-bound 125I-insulin at 37 degrees C was quantitated after rapidly dissociating surface-bound insulin with an acidic buffer (pH 3.0). Of the 23 protease inhibitors tested, only chymotrypsin substrate analogues inhibited insulin internalization. Internalization was decreased 62-90% by five different chymotrypsin substrate analogues: N-acetyl-Tyr ethyl ester, N-acetyl-Phe ethyl ester, N-acetyl-Trp ethyl ester, benzoyl-Tyr ethyl ester, and benzoyl-Tyr amide. The effect of the substrate analogues in inhibiting insulin internalization was dose-dependent, reversible, and required the full structural complement of a chymotrypsin substrate analogue. Cell surface receptor number was unaltered at 12 degrees C. However, concomitant with their inhibition of insulin internalization at 37 degrees C, the chymotrypsin substrate analogues caused a marked increase (160-380%) in surface-bound insulin, indicating trapping of insulin-receptor complexes on the cell surface. Additionally, 1 mM N-acetyl-Tyr ethyl ester decreased overall insulin degradation by 15-20% and also prevented the chloroquine-mediated increase in intracellular insulin, further indicating that surface-bound insulin was prevented from reaching intracellular chloroquine-sensitive degradation sites. The internalization of insulin receptors that were photoaffinity labeled on the cell surface with B2(2-nitro-4-azidophenylacetyl)-des-PheB1-insulin was also inhibited 70-90% by the five chymotrypsin substrate analogues, as determined by the effects of the analogues on the accumulation of trypsin-insensitive (intracellular) 440 kD intact labeled receptors. In summary, these results show that chymotrypsin substrate analogues efficiently inhibit the internalization of insulin and insulin receptors in adipocytes and implicate a possible role for endogenous chymotrypsin-like enzyme(s) or related substances in receptor-mediated endocytosis of insulin. PMID- 2877997 TI - Cloned cell lines from a transplantable islet cell tumor are heterogeneous and express cholecystokinin in addition to islet hormones. AB - A liver metastasis (MSL) with a remarkable in vitro proliferation potential has been identified in an NEDH rat carrying a transplantable x-ray-induced islet cell tumor. Two insulin-secreting cell lines, MSL-G and MSL-H, with doubling times of 3-5 d were established by repeated limiting dilution cloning. In vivo inoculation of MSL-G cells induced severe hypoglycemia caused by a small but highly heterogeneous tumor as revealed by immunocytochemistry. Whereas most cells stained for the islet hormones, insulin, glucagon, and somatostatin, clustered cells were discovered to contain cholecystokinin (CCK). Additional in vitro limiting dilution cloning, followed by immunocytochemical characterization, clearly demonstrated the capacity of single cell clones to simultaneously express the same four hormones. Radioimmunoassays with a panel of site-specific antisera of culture supernatants and purified cell extracts showed the MSL-G2 cells to produce, store, and secrete readily detectable amounts of processed and unprocessed CCK. Gastrin was not detected while coexpression of glucagon and CCK were demonstrated. Mutant clones selected for resistance to 6-thioguanine (frequency, 2 X 10(-7] and checked for HAT (hypoxanthine, aminopterin, thymidine) sensitivity retained the capacity for multi-hormone expression. We propose that the MSL tumor contains pluripotent endocrine stem cells. The MSL tumor and the MSL-G2 cells in particular will allow studies of not only CCK biosynthesis and processing but also of mechanisms involved in tumor and islet cell differentiation. PMID- 2877999 TI - Separation and determination of isopropamide iodide in pharmaceutical formulations by reversed-phase ion-pair high-performance liquid chromatography. AB - A stability-indicating determination for isopropamide iodide, an anticholinergic quaternary ammonium drug, in several pharmaceutical dosage forms by reversed phase ion-pair liquid chromatography is reported. The use of eluents containing both an amine as well as an alkylsulphonate proved to be very efficient for separating and determining quaternary ammonium drugs and related other basic drugs: adequate selectivity, excellent peak shape and good reproducibility (coefficient of variation, 1-2%) were obtained in a short analysis time. PMID- 2878000 TI - Determination of temazepam and its major degradation products in soft gelatin capsules by isocratic reversed-phase high-performance liquid chromatography. PMID- 2877998 TI - Lymphoma Thy-1 glycoprotein is linked to the cytoskeleton via a 4.1-like protein. AB - In this study we have found that the phosphoprotein doublet of 68,000 and 65,000 daltons (68/65 kD) in mouse T-lymphoma cells shares several structural and functional similarities with erythrocyte band 4.1. Our evidence for identifying the 68/65-kD doublet as a lymphoma 4.1-like protein is as follows: it displays an immunological cross-reactivity with anti-erythrocyte band 4.1 antibody; it exhibits a Svedberg unit of sedimentation coefficient of 4 S; it is phosphorylated in the presence of phorbol ester (phorbol-12-O tetradecanoylphorbol-13-acetate) and its phosphorylation requires Ca2+; it is phosphorylated primarily at serine residues; and it can bind directly to fodrin (a spectrin-like actin-binding protein). In addition, this lymphoma 4.1-like protein can be both colocalized and coisolated with the major T-lymphocyte specific glycoprotein, Thy-1 (gp 25). Therefore, all of these results strongly suggest that the lymphoma 4.1-like protein (68/65-kD doublet) may play a pivotal role in linking the Thy-1 (gp 25) glycoprotein to fodrin which, in turn, binds to the actin filaments that are responsible for recruiting Thy-1 antigens into cap structures. PMID- 2878001 TI - Conductometric monitoring of the amino acid oxidase reaction as a detector for high-performance liquid chromatography. AB - The deamination of L-amino acids by L-amino acid oxidase, which creates a change in the ionic strength of an HPLC eluent, is used to allow conductometric detection of L-amino acids. An example separation is given, and the conductometric method is compared to other methods of amino acid detection in the area of detection limits. Suggestions are also given for using this principle to create detectors based on other class selective enzymes. PMID- 2878002 TI - Identification and differentiation of beta-blockers and their metabolites in urine by computerized gas chromatography-mass spectrometry. AB - A method for the identification and differentiation of beta-blockers and their metabolites in urine after acid hydrolysis is described. The acetylated extract is analysed by computerized gas chromatography-mass spectrometry. An on-line computer allows rapid detection using ion chromatography with the ions of m/z 72, 86, 98, 140, 151, 159, 200 and 335. The identity of positive signals in the reconstructed ion chromatogram is confirmed by a comparison of the stored entire mass spectra with the reference spectra. The ion chromatogram, the reference mass spectra and the gas chromatographic retention indices (OV-101) are documented. References for the quantitation of the single beta-blockers are cited. PMID- 2878003 TI - Highly sensitive assay of benzodiazepine antagonist in plasma by capillary gas chromatography with nitrogen-selective detection. AB - A selective and highly sensitive capillary gas chromatographic method was developed for the determination of a benzodiazepine antagonist in human plasma. The analytical procedure involved extraction of the compound and its internal standard from basified plasma with n-butyl chloride-dichloromethane and chromatography of the extract on a DB-5 fused-silica column (30 m X 0.25 mm I.D.), applying automated splitless injection and nitrogen- phosphorus detection. The limit of quantification was about 50 pg/ml, using a 1-ml plasma specimen. The mean inter-assay precision was 2.6% in the concentration range 0.5-10 ng/ml. The method was shown to be specific with respect to various benzodiazepines and their main metabolites. The practicability of the method was demonstrated by the analysis of more than 300 plasma samples from a dose proportionality study performed with human volunteers. Owing to its high sensitivity, the new method can be used to obtain pharmacokinetic parameters of the benzodiazepine antagonist in man after doses near the envisaged therapeutic intravenous dose of less than 1 mg. PMID- 2878005 TI - High-performance fast affinity chromatographic purification of anti benzodiazepine antibodies. PMID- 2878004 TI - Determination of the new beta-blocker bisoprolol and of metoprolol, atenolol and propranolol in plasma and urine by high-performance liquid chromatography. AB - High-performance liquid chromatographic methods using fluorimetric detection have been developed for the determination in plasma and urine of bisoprolol, atenolol, metoprolol and propranolol. Bisoprolol, metoprolol and propranolol were extracted at alkaline pH with dichloromethane, atenolol with n-butanol-dichloromethane (25:75). After evaporation of the organic solvent the compounds were chromatographed on silica gel Si-60 columns (normal phase) using aqueous ammonium phosphate buffer (pH 4) containing 3-7% acetonitrile as eluent (method 1). Alternatively, the compounds were acetylated prior to chromatography on reversed phase columns (RP-8), using acetonitrile-water mixtures as eluents (method 2). The detection limit was 1-2 ng/ml in plasma and 10 ng/ml in urine for bisoprolol and metoprolol with either method. For atenolol the detection limit was 5 ng/ml in plasma or 50 ng/ml in urine (method 1), for propranolol 1 ng/ml in plasma (method 2). PMID- 2878006 TI - Liquid chromatography of reserpine and rescinnamine using electrochemical detection. PMID- 2878007 TI - Relationship between somatomedin-C and growth hormone levels in acromegaly: basal and dynamic evaluation. AB - The relationship between basal and stimulated plasma GH and somatomedin-C (SmC) levels in acromegalic patients was evaluated. The basal plasma SmC levels of 66 patients were significantly correlated (P less than 0.01) with mean daily plasma GH levels, but not with the percent GH increase after GH-releasing hormone or TRH or the GH decrease after acute bromocriptine administration. Bromocriptine (7.5 15 mg/day) administration for 9.2 +/- 0.9 (+/- SD) months in 20 patients significantly (P less than 0.05) decreased GH levels. SmC decreased significantly [from 9.8 +/- 1.9 to 5.1 +/- 0.7 U/ml (mean +/- SE)] only in the 10 patients who had the more marked GH inhibition. The administration of a somatostatin analog, SMS 201-995 (100 micrograms twice daily), to 12 patients for 16 weeks significantly decreased plasma GH and SmC levels beginning on the second day of therapy; normal SmC levels were achieved in 5 of 12 patients. Pituitary adenomectomy resulted in normal GH and SmC levels in 10 of 12 and 8 of 12 patients, respectively. Our data indicate an overall dependency of plasma SmC levels on plasma GH levels in acromegaly, although similar GH levels may have differing somatomedin-stimulating activities. A derangement in the feedback mechanisms controlling GH secretion is indicated by the failure of elevated SmC levels to influence the GH responsiveness to releasing hormones. In evaluating pharmacological or surgical treatments of acromegaly, a single plasma SmC value can reliably replace several plasma GH determinations. PMID- 2878008 TI - Serum type III procollagen propeptide levels in acromegalic patients. AB - Serum type III procollagen propeptide (PIIIP) is a reliable index of tissue collagen synthesis. Since in acromegaly there is increased collagen production, we measured serum PIIIP in acromegalic patients before any treatment (basal), during medical treatment with the somatostatin analog SMS 201-995, and after pituitary adenomectomy. In all patients, serum GH and plasma somatomedin-C (SmC) levels were also measured. Basal serum PIIIP levels were significantly (P less than 0.01) higher in acromegalic patients (mean +/- SEM, 22.7 +/- 2.1 ng/ml) than in normal subjects (n = 30; 9.7 +/- 0.5 ng/ml), and they were significantly correlated with plasma SmC values (r = 0.31; P less than 0.05). A significant (P less than 0.01) reduction in PIIIP levels occurred in patients treated with SMS 201-995 or surgery (from 24.3 +/- 2.7 to 12.4 +/- 1 ng/ml) as well as in GH and SmC levels. The maximum percent decrease in serum PIIIP was significantly correlated with those in GH (r = 0.65; P less than 0.01) and SmC (r = 0.60; P less than 0.01). Serum PIIIP levels did not change in those patients in whom neither GH nor SmC were decreased by treatment. In conclusion, serum PIIIP levels are elevated in acromegalic patients, and they decline in parallel with GH and SmC during medical or surgical treatment. Serum PIIIP measurements may be useful in the evaluation of acromegalic patients to gain information on the biological activity of GH and in monitoring the course of the disease. PMID- 2878009 TI - The response of serum growth hormone levels to the long-acting somatostatin analog SMS 201-995 in acromegaly. AB - SMS 201-995 (SMS) is a long-acting analog of somatostatin. We studied the effect of SMS (50-100 micrograms, sc, every 8 h) on serum GH in five patients with acromegaly. Serum GH decreased significantly in four of the five patients 4 h after SMS treatment. In two of the four patients, this reduction was not sustained for 7 h, but sustained reduction to normal GH concentrations did occur in the two patients who had basal serum GH levels below 15 ng/ml. In the two patients whose responses were not sustained for 7 h, a higher dose of SMS did not cause sustained reduction in GH. SMS was well tolerated, except for one episode of elevated serum aminotransferase levels. These results indicate that SMS induced reductions in serum GH in patients with acromegaly are often not sustained despite SMS administration every 8 h and indicate that the insufficient duration of effect may limit its therapeutic efficacy. PMID- 2878010 TI - Impaired carboxylation of osteocalcin in warfarin-treated patients. AB - The total circulating osteocalcin and ratio of inactive (noncarboxylated; GLU) to active (carboxylated; GLA) form of circulating osteocalcin were measured in patients receiving long term warfarin treatment (n = 20), age-matched control patients not receiving warfarin treatment (n = 10), and normal subjects before and after the administration of 30 mg warfarin (n = 7). There was no significant difference in the total osteocalcin concentrations between the control patients and the patients receiving long term warfarin treatment, and it did not significantly change after warfarin ingestion in the normal subjects. The GLU/GLA ratio was significantly increased (P less than 0.002) in the patients receiving long term warfarin treatment compared with that in the control patients. There was a significant increase (P less than 0.01) in the GLU/GLA ratio after warfarin ingestion in the normal subjects. This study demonstrates that osteocalcin carboxylation in humans is a vitamin K-dependent process and that circulating osteocalcin is structurally altered by warfarin administration. This finding has pathophysiological implications for the fetal warfarin embryopathy syndrome, bone disease associated with chronic liver diseases, and possibly for osteoporosis, in which vitamin K deficiency has been implicated. PMID- 2878012 TI - Analysis of hospital-formulated oral liquid preparations by second derivative ultraviolet spectroscopy. AB - Second derivative ultraviolet spectrophotometric methods have been devised for the analysis of hospital-formulated oral liquid preparations. These rapid techniques are useful in the routine quality control of oral liquid formulations where direct spectrophotometric determination of the drug analyte is precluded by interference from formulation excipients and colouring agents. This report describes examples in which the active principles of a dipipanone mixture, a methadone mixture and an orphenadrine syrup were determined by derivative spectroscopy. In each case spectral interference from formulation excipients was abolished. The accuracy, precision and specificity of each method has been established. PMID- 2878013 TI - Hypercalcaemia in T cell acute lymphoblastic leukaemia: report of two cases. AB - Two young adults presenting with acute lymphoblastic leukaemia (ALL) associated with hypercalcaemia and osteolytic lesions were both found to have T cell ALL. Hypercalcaemia is a rare feature of ALL and has not previously been related to T cell disease. Both cases, in some respects, resembled (age between 10 and 20 years and low white cell count) the few other previously reported cases. In one of our cases increased concentrations of vitamin D3 seemed to have a role in the pathogenesis of the hypercalcaemia. PMID- 2878011 TI - The immunologic basis of inflammatory bowel disease. PMID- 2878015 TI - Drugs in exacerbation of psoriasis. AB - Drugs that have been associated with the precipitation or exacerbation of psoriasis include lithium, beta adrenergic receptor blocking agents, and antimalarials. The withdrawal of corticosteroids has been reported to activate pustular psoriasis. Nonsteroidal anti-inflammatory drugs, such as indomethacin, have recently been reported to exacerbate psoriasis, although additional well controlled studies are still needed. Drugs used for treatment of psoriasis will sometimes cause a flare because of irritation, phototoxicity, or hypersensitivity reaction resulting in a Koebner phenomenon. Because psoriasis is a very complex disease and its activity is often unpredictable, clinical studies on adverse drug effects on psoriasis have been difficult to conduct. This review evaluates clinical, histologic, and biochemical evidence in the literature for drug associated onset or exacerbation of psoriasis. PMID- 2878014 TI - Synaptic relationships between neurons containing vasopressin, gastrin-releasing peptide, vasoactive intestinal polypeptide, and glutamate decarboxylase immunoreactivity in the suprachiasmatic nucleus: dual ultrastructural immunocytochemistry with gold-substituted silver peroxidase. AB - In order to examine the morphological substrates for neuronal connections between cells of the hypothalamic suprachiasmatic nucleus (SCN) that contain immunoreactivity for different neurotransmitters, a double ultrastructural immunocytochemical analysis was used. For double immunostaining, the first neuroactive substance antigen was labeled with gold-substituted silver intensified peroxidase (GSSP), which results in a granular gold deposit of high electron and light opacity. The second antigen was labeled with peroxidase and a diaminobenzidine chromagen. The GSSP reaction product greatly increased the visibility of immunoreactive structures, with both light and electron microscopy. Intensification with the GSSP method worked at all depths of thick tissue sections as determined with analysis of immunostained sections cut perpendicular to their flat surface, and with analysis of thick 80-micron sections of brain tissue into which horseradish peroxidase (HRP) has been microinjected. On a nitrocellulose dot-blot comparison of different substrates for HRP, the GSSP intensification compared favorably with tetramethylbenzidine, but unlike tetramethylbenzidine, the GSSP was stable in a wide range of buffers. In addition to diaminobenzidine, the GSSP reaction was used to intensify and stabilize both the Hanker-Yates reagent and tetramethylbenzidine on the nitrocellulose model system. Through the use of the GSSP reaction, five new synaptic relationships in the suprachiasmatic nucleus were revealed. By increasing the sensitivity of the peroxidase method by silver-gold intensification, immunoreaction product could be found in dendrites at a greater distance from the perikaryon than in nonintensified material. Because of this greater sensitivity, the neuroactive substance contained in the cell of origin of a dendrite could sometimes be identified. Boutons immunoreactive for vasopressin-associated neurophysin were found to make synaptic contact with postsynaptic dendrites that also contained vasopressin-neurophysin immunoreactivity. Similarly, boutons containing gastrin releasing peptide immunoreactivity made synaptic contact with cells also exhibiting gastrin-releasing peptide immunoreactivity. Neurons stained with GSSP reaction product could be easily discriminated from those containing only HRP precipitated diaminobenzidine, allowing the simultaneous use of these two markers in the same 30-micron tissue section and subsequently in ultrathin sections for electron microscopy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2878016 TI - The effects of combined H1 and H2 histamine antagonists on alterations in nasal airflow resistance induced by topical histamine provocation. AB - A clinical trial was undertaken to assess the effects of oral H1 (diphenhydramine hydrochloride) and H2 (cimetidine) histamine blockade on nasal resistance induced by topical histamine. Ten adult volunteers were tested on two separate occasions. Their noses were pretreated by oral administration of either combined H1 and H2 histamine antagonists or H1 antagonist and placebo. The nasal airflow resistive response to topical histamine was then determined. Combined histamine antagonism was significantly more effective in reducing the nasal resistive response to topical histamine than H1 antagonist alone (p less than 0.0001). Furthermore, ingestion of the oral H1 histamine antagonist, diphenhydramine hydrochloride, alone led to an increase in resistance of the unprovoked nose, whereas combined H1 and H2 antagonism did not lead to a significant change. PMID- 2878017 TI - Effect of afferent renal nerve stimulation on blood pressure, heart rate and noradrenergic activity in conscious rats. AB - The effects of electrical stimulation of afferent renal nerves on arterial pressure, heart rate, and alpha-methyltyrosine-induced disappearance of norepinephrine in the hypothalamus, contralateral kidney, intestine, and skeletal muscle were studied in conscious rats. There was a significant increase in arterial pressure in response to afferent renal nerve stimulation. There was no significant change in the turnover of norepinephrine in the hypothalamus. However, there was a significant increase in the turnover of norepinephrine in the skeletal muscle, a tendency toward an increase in the intestine, and no change in the contralateral kidney. These results indicate that activation of afferent renal nerve fibers does not change noradrenergic activity in the hypothalamus yet produces a differential sympathetic outflow. Secondly, the increased turnover of norepinephrine in skeletal muscle may be contributing to the increase in arterial pressure. PMID- 2878019 TI - [Dental application of titanium and its alloy]. PMID- 2878018 TI - Inherited homeotic midfacial malformations in Burmese cats. AB - During the past three decades, Burmese cats have been selected for a shorter muzzle and a more rounded face. Recently there arose a line of these animals that consistently exhibit such a brachycephalic appearance; unfortunately, approximately 25% of these kittens are born with a neonatal lethal midfacial malformation. The abnormality is characterized by agenesis of all derivatives of the medial nasal prominence; lateral duplication of most derivatives of the maxillary process; including the canine teeth and whiskers fields; telencephalic meningoencephalocele; and secondary ocular degeneration. The anatomy, embryology, and pattern of inheritance of this unique midfacial malformation are described. PMID- 2878020 TI - Ectopic gastric mucosa in proximal esophagus. Its clinical significance and hormonal profile. AB - We have found 20 cases of ectopic gastric mucosa in the proximal esophagus. Five patients had symptoms, usually a burning sensation in the neck and/or dysphagia. We report the results of immunoperoxidase staining of this tissue for gastrin, somatostatin, vasoactive intestinal peptide, and bombesin. In 85% of biopsy specimens tested, one or more polypeptides were present. Gastrin and bombesin were found more frequently in symptomatic patients, and somatostatin in asymptomatic patients. Chronic inflammatory changes were more frequent in symptomatic patients. PMID- 2878021 TI - Chromogranin A in the pancreatic islet: cellular and subcellular distribution. AB - Chromogranin A (CGA) is the major soluble protein within secretory vesicles of chromaffin cells. A polyclonal antiserum was raised against bovine CGA and characterized in two-dimensional immunoblots. Cellular and subcellular distribution of CGA in bovine pancreatic islet was investigated by immunocytochemistry. At the light microscopic level, CGA-like immunoreactivity was found in the same cells that react with antibodies against insulin, glucagon, and somatostatin. A minority of cells containing pancreatic polypeptide also showed faint immunostaining. At the ultrastructural level (protein A-gold technique), CGA-like immunoreactivity was confined exclusively to the secretory vesicles. Whereas the hormones were localized mainly in the central part of the secretory vesicles, CGA was present predominantly in the periphery. These findings indicate that a CGA-like protein is a regular constituent of the matrix of secretory vesicles in pancreatic endocrine cells. PMID- 2878022 TI - Immunocytochemical localization of D-amino acid oxidase in the central clear matrix of rat kidney peroxisomes. AB - Light and electron microscopic localizations of D-amino acid oxidase (DAO) in rat kidney was investigated using immunoenzyme and protein A-gold techniques. The enzyme was purified from rat kidney homogenate and its antibody was raised in rabbits. By Ouchterlony double-diffusion analysis and immunoblot analysis with anti-(rat kidney DAO) immunoglobulin, the antibody was confirmed to be monospecific. The tissue sections (200 micron thick) of fixed rat kidney were embedded in Epon or Lowicryl K4M. Semi-thin sections were stained for DAO by the immunoenzyme technique after removal of epoxy resin for LM, and ultra-thin sections of Lowicryl-embedded material were labeled for DAO by the protein A-gold technique for EM. By LM, fine cytoplasmic granules of proximal tubule were stained exclusively. Among three segments of proximal tubules, and S2 and S3 segments were heavily stained but the S1 segment only weakly so. By EM, gold particles indicating the antigenic sites for DAO were exclusively confined to peroxisomes. Within peroxisomes, the gold particles were localized in the central clear matrix but not in the peripheral tubular substructures. The results indicate that D-amino acid oxidase in rat kidney is present exclusively in peroxisomes in the proximal tubule and that within peroxisomes it is found only in central clear matrix and not in the peripheral tubular substructures. PMID- 2878023 TI - Role of the microbiologist in the management of patients with blood disorders. PMID- 2878024 TI - Hygiene for hydrotherapy pools. PMID- 2878025 TI - Contamination of intravenous infusion systems--the effect of changing administration sets. AB - Intravenous administration sets were changed at varying time intervals between every 24 h and 120 h in 387 patients. The rates of intraluminal contamination of the cannulae and of local inflammation were measured in relation to the time interval between changing sets. There was no correlation between phlebitis and intraluminal contamination, but a significant association was found between phlebitis and fever, infusion of potassium at greater than 10 mmol l-1, Venflon type 140 and infusion of blood or intralipid. No correlation was found between septicaemia and intraluminal contamination of the infusion systems. Contamination of cannulae increased slightly with time, but this was not statistically significant. We conclude that there will be no clinical benefit by daily changing of administration sets, compared with changing up to every fifth day. PMID- 2878027 TI - Serious postoperative infections caused by coagulase-negative staphylococci: an epidemiological and clinical study. AB - We have reviewed all 3577 nosocomial infections occurring at our institution over a 49-month period and found coagulase-negative staphylococci (CNS) associated with 297. Seventy-eight of 193 CNS tested for antibiotic sensitivity were multiple-drug resistant (MR-CNS). There were 19 well-documented serious postoperative CNS infections including nine ventricular, seven bloodstream and three peritoneal infections. Each was associated with an indwelling device and 11 of the infections involved MR-CNS. Antibiotic therapy with or without removal of the device resulted in cure of all patients. Air samples taken during various surgical procedures frequently were positive for CNS but rarely revealed MR-CNS. Our results cause concern regarding current antibiotic prophylaxis regimens. PMID- 2878026 TI - Problems in the investigation of an apparent outbreak of coagulase-negative staphylococcal septicaemia following cardiac surgery. AB - Two hundred and twenty-six hospital staff and patients were investigated for the carriage of gentamicin-resistant coagulase-negative staphylococci (CNS) during an apparent outbreak of infection after cardiac surgery. Of the four index strains from infected wounds, three were indistinguishable. The carriage of similar organisms was widespread, particularly among ITU staff (72%) and patients. Ninety one of the 296 gentamicin-resistant isolates were further investigated, and of these 33 were indistinguishable from index strains even with the use of specialized techniques. Our experience indicates that in outbreaks of infection caused by gentamicin-resistant CNS, resources should be focused on the interruption of transmission and prevention of introduction of these organisms to susceptible patients. PMID- 2878028 TI - The prediction of abdominal surgical wound infection: the value of an enrichment broth for initial culture of operative parietal swabs. AB - At the conclusion of 817 abdominal operations, duplicate swabs were taken from the subcutaneous tissues for microbiological examination; one swab was transported to the laboratory in Stuart's thioglycollate medium and the other immediately incubated in Robertson's cooked meat broth. The latter method resulted in significantly more isolations of potentially pathogenic bacteria than the former, (31% compared with 17%, P less than 0.001). Immediate culture in broth with subsequent subculture allowed more accurate prediction of patients at risk of wound infection; using this method we found a 1:3 likelihood of wound infection with a 5% chance of severe infection when a single pathogenic species was cultured, and a 1:2 likelihood of wound infection with a 10% chance of severe infection when two or more pathogenic species were cultured. Transport of swabs in thioglycollate medium, in contrast, detected fewer patients with parietal contamination and showed a 1:5 likelihood of wound infection when the swab was sterile and a 1:2 chance when one or more than one pathogenic species was cultured. PMID- 2878029 TI - Toewebs as a source of gram-negative bacilli. AB - The prevalence of Gram-negative bacilli on the toewebs was 8% in normal students, 24% in hospital outpatients with suspected Tinea pedis, 41% in industrial workers wearing protective clothing and 58% in coal miners. Prevalence was greatest in those exposed to wet working conditions. In miners, the presence of Gram-negative bacilli was related to symptoms of itching/soreness and cracking/fissuring, and was negatively related to malodour, but this latter trend was reversed in outpatients and in industrial workers. The feet are a source of many 'enteric' and 'environmental' bacilli and could contribute to infection elsewhere than in the toewebs themselves. PMID- 2878030 TI - Single dose intra-operative antimicrobial prophylaxis during prostatectomy: gentamicin compared with cefotetan. AB - Two hundred consecutive patients undergoing prostatectomy were given a single dose of gentamicin or cefotetan intra-operatively. Both antibiotics afforded good protection against postoperative bacteriuria and septicaemic symptoms were fewer in those patients given cefotetan, although this difference was not statistically significant. PMID- 2878032 TI - The use of alcoholic paper wipes for routine hand cleansing: results of trials in two hospitals. AB - The use of alcoholic paper hand wipes by nursing staff was assessed in two trials. No significant changes in total viable counts from finger imprint samples were observed when wipes were used, but some decrease in samples positive for Enterobacteriaceae and Staphylococcus aureus was recorded. The wipes were found to be pleasant and convenient to use. It is concluded that wipes are an acceptable alternative to soap and water for routine hand cleansing. PMID- 2878031 TI - Antiseptic toxicity in wounds healing by secondary intention. AB - The effects of two commonly used antiseptics for chronic ulcer care, chloramine T and chlorhexidine, on the biochemical and histological parameters of healing have been examined. The antiseptics were compared with saline when applied to 10 mm skin defects on Sprague-Dawley rats. Chloramine T significantly delayed the production of collagen and prolonged the acute inflammatory response compared with saline. Chlorhexidine did not differ from saline. We conclude that hypochlorite antiseptics may adversely affect healing by secondary intention and the antibacterial and desloughing action of agents should be carefully balanced against their toxic effect. PMID- 2878033 TI - An outbreak of nosocomial cholera in a rural Bangladesh hospital. AB - At a time of year when Vibrio cholerae infection accounted for over 50% of admissions to a rural Bangladeshi diarrhoea treatment centre, 29% of 48 patients hospitalized with non-cholera diarrhoea developed nosocomial V. cholerae infection. During an investigation of the 8-week outbreak, only the severity of the non-cholera diarrhoea which prompted hospital admission emerged as an important risk factor for nosocomial infection; food, intravenous solutions, oral rehydration fluid, patient attendants and hospital personnel could not be implicated as transmission sources. Patients receiving antibiotics while hospitalized did not develop nosocomial infection. Antecedent non-cholera diarrhoea may represent an important risk factor in some cases of V. cholerae infection occurring in persons who reside in cholera-endemic areas where rates of non-cholera diarrhoea are also high. PMID- 2878034 TI - Randomized clinical trial of intra-operative antimicrobial prophylaxis of infection after neurosurgical procedures. AB - A randomized, placebo-controlled, double-blind and sequentially analysed clinical trial to determine the efficacy of intra-operative parenteral gentamicin and vancomycin (with streptomycin in the irrigating solution) in preventing infection at the operative site following neurosurgical procedures is described. Patients receiving prophylaxis had a significantly (P = 0.046) lower operative site infection rate (2/71 = 2.8%) than those receiving placebo (9/77 = 11.7%). This difference was most apparent during an epidemic, the source of which was not evident. Moreover, a total of 13 infections (two operative site, five pneumonia and six urinary tract) occurred among 12 patients receiving prophylaxis, whereas there was a total of 31 infections (nine operative site, nine pneumonia, 10 urinary tract and three septicaemia) among 24 patients receiving placebo. A smaller quantity of antimicrobial drugs was administered postoperatively to patients receiving prophylaxis (3.96 'antibiotic-days' per patient) than to those receiving placebo (6.87 'antibiotic-days' per patient). PMID- 2878035 TI - An outbreak of gastroenteritis in a psycho-geriatric hospital associated with a small round structured virus. AB - An outbreak of gastroenteritis in a psycho-geriatric hospital is described. Small round structured viruses, morphologically similar to Norwalk agent, were seen in stool samples from four patients. Although the illness was mild, 67 patients and 30 nurses on four wards were affected over a period of 4 weeks. Because of shortage of staff and isolation facilities, difficulty was experienced in introducing effective control measures. PMID- 2878036 TI - A study of some factors associated with wound infection. AB - Five hundred and four surgical patients were studied at Princess Basma Hospital, North Jordan, during the period April 1984-January 1985. The overall postoperative wound infection rate was 3.6%. In clean surgery 1.1% of wounds were infected and in potentially contaminated and contaminated surgery the infection rate was 3.3% and 18.5% respectively. Major organisms isolated from infected wounds were Staphylococcus aureus (55.5%), Escherichia coli (16.6%), Proteus vulgaris (11.1%), Pseudomonas aeruginosa, Enterobacter aerogenes and Aeromonas hydrophilia, each with 5.6%. Use of a wound drain, duration of operation and carriage of Staph. aureus by the patient were associated with a higher frequency of wound infection. PMID- 2878037 TI - Use of a simple exhaust fan to control airborne transmission of varicella zoster. PMID- 2878038 TI - Evaluation of the 'NUK-2000 Steam Steriliser', an alternative baby bottle disinfector. PMID- 2878039 TI - Use of 'Signal System' (Oxoid) for diagnosing infection in continuous ambulatory peritoneal dialysis. PMID- 2878040 TI - Aeromonas in hospital--methods of isolation. PMID- 2878041 TI - Movement of intravenous cannulae--flexible sidearm vs. fixed sideport. PMID- 2878042 TI - The antigenic analysis of haemorrhagic fever with renal syndrome viruses in China by monoclonal antibodies. AB - Thirty-six strains of haemorrhagic fever with renal syndrome (HFRS) virus were isolated from patients and a number of host animals in various areas in China. They were analysed by an immunofluorescence test (IFAT) using 10 monoclonal antibodies (McAbs) specific for the HFRS virus; antigenic differences among the strains have been demonstrated. The HFRS virus strains revealed nine different reactions with the McAbs, showing that there are at least nine different antigenic determinants including group-, type- and strain-specific. Analysis of the results shows that antigenic differences among the HFRS virus strains are mainly related to differences in the host animals. PMID- 2878043 TI - Lymphoid bone marrow cultures can reconstitute heterogeneous B and T cell dependent responses in severe combined immunodeficient mice. AB - Long-term lymphoid bone marrow cultures (LBMC) produce B lymphocytes and their precursors for several months in vitro. To assess their differentiative potential and determine their capacity to function as immune effectors, cells from the cultures were transplanted into mice with severe combined immune deficiency disease (SCID). SCID mice are deficient in T and B lymphocytes and are serum immunoglobulin (Ig) negative, but grafts of normal lymphoid precursors can expand and differentiate in them, thereby restoring immunocompetence. The results of these studies indicate that cells from LBMC are able to reconstitute splenic B lymphocytes in the SCID mice. Upon in vivo transfer, LBMC cells secreted Ig that displayed isotype distribution and a pattern of heterogeneity comparable with normal BALB/c mice, as determined by two-dimensional gel electrophoresis. The transplanted LBMC cells were functional, because reconstituted mice could respond to immunization with the T-independent antigen TNP-Ficoll. The results also indicate that cultured cells could reconstitute T cell activity in SCID mice. Splenocytes from approximately one-third of the recipients could generate a cytotoxic response to alloantigens after 5 days of sensitization in a mixed lymphocyte culture, and all reconstituted SCID mice could respond to immunization with the T cell-dependent antigen TNP-BSA. These results demonstrate that B cells, as well as T cell activity, are present in LBMC-reconstituted SCID mice, and show that LBMC cells have the capacity to mediate an immune response. PMID- 2878044 TI - Transforming growth factor beta is an important immunomodulatory protein for human B lymphocytes. AB - The growth and differentiation of B cells to immunoglobulin (Ig)-secreting cells is regulated by a variety of soluble factors. This study presents data that support a role for transforming growth factor (TGF)-beta in this regulatory process. B lymphocytes were shown to have high-affinity receptors for TGF-beta that were increased fivefold to sixfold after in vitro activation. The addition of picogram quantities of TGF-beta to B cell cultures suppressed factor dependent, interleukin 2 (IL 2) B cell proliferation and markedly suppressed factor-dependent (IL 2 or B cell differentiation factor) B cell Ig secretion. In contrast, the constitutive IgG production by an Epstein Barr virus-transformed B cell line was not modified by the presence of TGF-beta in culture. This cell line was found to lack high-affinity TGF-beta receptors. The degree of inhibition of B cell proliferation observed in in vitro cultures was found to be dependent not only on the concentration of TGF-beta added but also on the concentration of the growth stimulatory substance (IL 2) present. By increasing the IL 2 concentrations in culture, the inhibition of proliferation induced by TGF-beta could be partially overcome. In contrast, the inhibition of Ig secretion induced by TGF-beta could not be overcome by a higher concentration of stimulatory factor, demonstrating that the suppression of B cell differentiation by TGF-beta is not due solely to its effects on proliferation. Furthermore, it was demonstrated that B lymphocytes secrete TGF-beta. Unactivated tonsillar B cells had detectable amounts of TGF-beta mRNA on Northern blot analysis, and B cell activation with Staphylococcus aureus Cowan (SAC) resulted in a twofold to threefold increase in TGF-beta mRNA. Supernatants conditioned by unactivated B cells had small amounts of TGF-beta, SAC activation of the B cells resulted in a sixfold to sevenfold increase in the amount of TGF-beta present in the supernatants. Thus, B lymphocytes synthesize and secrete TGF-beta and express receptors for TGF-beta. The addition of exogenous TGF-beta to cultures of stimulated B cells inhibits subsequent proliferation and Ig secretion. TGF-beta may function as an autocrine growth inhibitor that limits B lymphocyte proliferation and ultimate differentiation. PMID- 2878045 TI - Expression of immunoglobulin lambda light chain by the promyelocytic cell line HL 60. AB - The HL-60 cell line, established from a patient with acute promyelocytic leukemia, can be induced to undergo differentiation along the granulocyte or monocyte/macrophage line, depending on the particular inducer that is used. In this communication we provide evidence that HL-60 cells also have B lymphoid characteristics because by flow cytometry and clonal excess calculations, these cells are found to express immunoglobulin (Ig) lambda light chains on their surface. Furthermore, HL-60 cells contain poly(A)+ RNA that hybridizes with a DNA fragment encoding the constant region of Ig lambda chains and comigrates with lambda mRNA on RNA blots. Treatment of HL-60 cells with a phorbol ester that induces monocyte/macrophage differentiation resulted in the loss of surface Ig lambda chains and lambda RNA. PMID- 2878047 TI - Molecular mapping of murine I region recombinants. II. Crossing over in the E beta gene is restricted to a 4.5 kb stretch of DNA that excludes the beta 1 exon. AB - The crossing over in five murine I-region recombinants (Is/Ik) was studied by restriction fragment length polymorphism analysis after Southern blot hybridization by using I-region-specific probes. These recombinants included three recently developed strains, B10.ASR1, B10.ASR11, and B10.ASR12; and two strains B10.S(9R) and B10.HTT derived earlier. Although these recombinants were reciprocal in haplotype orientation to the three recombinants we reported recently, these too crossed over within the same 7 kb stretch of DNA in the E beta gene. This 7 kb stretch of DNA included the 3' half of the first intron, the beta 1 exon, the second intron, and the beta 2 exon. A comparison of the cDNA sequences of the two parental E beta alleles revealed that although the beta 2 exons were identical, there were several nucleotide differences between the two beta 1 exons. This allowed us to determine the parental origin of the beta 1 exon in the recombinants at the level of transcription by using S1 nuclease mapping. Thus we were able to show that in each case the 3' portion of the first intron and the beta 1 exon were upstream from the site of crossover. All eight recombinants involving the k and s haplotypes now can be mapped within a 4.5 kb stretch of DNA, which includes only the beta 1-beta 2 intron and the beta 2 exon of the E beta gene. These findings imply that the I-E molecules expressed in these recombinants will probably have conserved sequences and therefore will exhibit identical I-E-restricted immune responses, despite the fact that crossing over could have occurred at different sites within the beta 1-beta 2 intron. PMID- 2878046 TI - Chromosomal location of the genes encoding complement components C5 and factor H in the mouse. AB - Complementary DNA probes corresponding to the factor H and C5 polypeptides have been used to determine the chromosomal localizations of these two complement components. Both probes revealed complex and polymorphic arrays of DNA fragments in Southern blot analysis of mouse genomic DNA. Following the distribution of these bands in panels of somatic cell hybrids carrying various combinations of mouse chromosomes on a constant rat or Chinese hamster background allowed the localization of the C5-associated fragments to proximal chromosome 2 and the localization of the factor H-associated fragments to chromosome 1 or chromosome 3. Following the inheritance of DNA restriction fragment-length polymorphisms revealed by the probes in recombinant inbred mouse strains allowed the factor H associated fragments to be mapped to Sas-1 on chromosome 1, and the C5-associated fragments to be mapped to Hc. Analysis of three-point crosses, in turn, placed the latter locus 19 cM distal to Sd on chromosome 2. We have designated the two loci Cfh and C5, respectively. This genetic analysis raises the possibility that C5 and factor H are both encoded by complex loci composed of distinct structural and regulatory genes. PMID- 2878048 TI - Quantitation of tissue transglutaminase by a sandwich ELISA system. AB - A sandwich ELISA system has been developed to quantitate transglutaminase in human cell extracts. It utilizes affinity-purified rabbit anti-human transglutaminase as the capture antibody and a mouse monoclonal anti transglutaminase (Birckbichler et al., 1985) as the indicator antibody (together with peroxidase-labeled anti-mouse immunoglobulin). The sensitivity of the assay was less than 1.0 ng/mg cellular protein. Significantly higher concentrations of the enzyme were found in resting versus proliferating or transformed fibroblasts in good agreement with previous activity measurements. The levels of transglutaminase in normal T and B lymphocytes, malignant lymphoid cells and monocytes were also determined. PMID- 2878049 TI - Optimal methods for generating expanded lymphokine activated killer cells capable of reducing established murine tumors in vivo. AB - The systemic administration of lymphokine activated killer (LAK) cells and recombinant interleukin-2 (RIL-2) is effective in reducing the number of established pulmonary and hepatic metastases from multiple murine tumors and has recently been shown to be effective in mediating the regression of metastatic cancer in humans as well. The generation of sufficient numbers of LAK cells for the effective therapy of human tumors remains a major obstacle to the widespread application of this immunotherapeutic approach. We have thus studied methods for the in vitro expansion of LAK cells effective in immunotherapy. Our previous studies used LAK cells generated in culture with RIL-2 for 3 days. LAK cells cultured in RIL-2 for 5 or 7 days were not significantly different from cells cultured for 3 days either in the number of cells obtained, their in vivo cytotoxicity or their in vivo therapeutic effectiveness. When day 3 LAK cells were transferred to fresh culture medium containing 1000 U/ml of RIL-2, a highly reproducible expansion of these cells was obtained. By day 5, cell numbers expanded 9.6 +/- 0.8-fold (mean +/- SEM; n = 36) and by day 8, cells expanded 15.1 +/- 1.0-fold (n = 19). In 4 h 51Cr release assays against fresh tumor target cells, day 3 LAK cells had a mean of 13 lytic units/10(6) cells in 24 experiments. Day 5 expanded LAK cells had a mean of 30 lytic units/10(6) cells in 13 experiments (P less than 0.05 compared to day 3 LAK cells) and day 8 expanded LAK cells had a mean of 11 lytic units/10(6) cells in 6 experiments (P = NS compared to day 3 LAK cells) When day 5 and day 8 expanded LAK cells were infused in vivo with RIL-2, they were found to significantly reduce the number of experimentally induced pulmonary metastases as effectively as non-expanded conventional day 3 LAK cells. Similar findings were documented in experiments against hepatic metastases. These experiments demonstrate that LAK cells could expand a mean of 15-fold in vitro in RIL-2 and maintain their anti-tumor therapeutic effectiveness when adoptively transferred. These experiments suggest methods for generating increased numbers of cells for use in the adoptive immunotherapy of human cancers and may substantially reduce the need for repeated leukophereses of cancer patients undergoing this therapy. PMID- 2878050 TI - Distribution of Lambornella clarki (Ciliophora: Tetrahymenidae) and other mosquito parasites in California treeholes. PMID- 2878051 TI - Inhibitory effects of shale oils (Ichthyols) on the secretion of chemotactic leukotrienes from human leukocytes and on leukocyte migration. AB - Ichthyols are sulfated shale oils with well-known anti-inflammatory effects in dermatologic diseases. Their possible mechanisms of action were studied by measuring chemotactic factor release from peripheral human leukocytes in vitro. Ichthyols caused no release of such factors by themselves but inhibited ionophore induced release. After elution of the cell supernatants on reverse-phase high pressure liquid chromatography, followed by analysis of the fractions in the chemotaxis assay and the radioimmunoassay, Ichthyols caused a reduction of lipids at marker positions for leukotriene B4 (LTB4) and 20-COOH-LTB4. The inhibition was also evident in the LTB4 radioimmunoassay, was dose- and time-dependent, and occurred in noncytotoxic concentrations of the agents. Ichthyols also inhibit the chemotactic response of neutrophils toward LTB4 and the unstimulated migration of cells. These inhibitory effects of Ichthyols on secretion of chemotactic arachidonate metabolites from leukocytes and on cell migration provide a plausible explanation for their anti-inflammatory activity. PMID- 2878052 TI - [Treatment of circulatory diseases: recent progress. 4. Cardiomyopathies]. PMID- 2878053 TI - [Treatment of angina pectoris]. PMID- 2878054 TI - [A clinico-pathological study of allergic granulomatous angitis--on our experience of three cases and literature review of 56 cases reported in Japan]. PMID- 2878055 TI - Effects of histamine H1- and H2-receptor antagonists on thyrotrophin secretion in the rat. AB - The effects of histamine H1- and H2-receptor antagonists on the pituitary-thyroid axis were studied in normal and thyroxine (T4)-treated rats. Acute administration (120 min before the test) of the H2 antagonist cimetidine induced a significant (P less than 0.01) increase in the TSH response to TRH, whereas treatment with histamine (30 min before the test) or with the H1-receptor blocker diphenhydramine (120 min before the test) was without effect. Treatment with cimetidine or ranitidine (another H2-receptor antagonist) for 5 days induced a marked decrease in basal plasma TSH concentrations (P less than 0.01), with no changes in pituitary concentrations of TSH. Plasma prolactin concentrations were similarly decreased by cimetidine (P less than 0.01), though not by ranitidine. Neither antihistaminic altered pituitary prolactin concentrations. Despite decreasing basal concentrations of plasma TSH, cimetidine augmented the response to TRH above baseline values (P less than 0.01) in control rats as well as in animals with T4-induced suppression of plasma TSH. Administration of cimetidine or ranitidine for 5 days was followed by a reduced concentration of plasma T4 and triiodothyronine (T3) (P less than 0.05 and P less than 0.01 respectively), perhaps as a result of the declining plasma TSH levels. These results provide the first evidence for the reduction of plasma TSH concentrations by H2-receptor blockers, and may indicate that histamine can physiologically regulate TSH and prolactin secretion through H2 receptors in the anterior pituitary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878056 TI - An in-situ isolated rat adrenal perfusion system for study of neurally mediated catecholamine secretion: effects of morphine, a Met-enkephalin analogue, and naloxone on catecholamine secretion. AB - An in-situ isolated rat adrenal perfusion technique has been devised to study the opioid control of neurally mediated adrenomedullary catecholamine release. Adrenomedullary catecholamine secretion was induced by electrical stimulation of the cut end of the left descending thoracic sympathetic chain on platinum electrodes. The half-maximal stimulatory potential (ED50) of the system was 8 V, 20 Hz, with 300 microseconds pulse width. Basal release of catecholamine from the adrenal was constant using a perfusion flow rate of 100-300 microliter/min, but increased significantly with increasing perfusion temperature over the range 36 38 degrees C. Following repetitive 30-s stimulation of the left thoracic sympathetic chain, and 3-min fraction collections, the total amount of catecholamine released per fraction remained within 80-100% of the maximum release for up to eight consecutive stimuli. The release of catecholamines was completely blocked by hexamethonium (0.1 mmol/l), but recovered to pre-blockade values within two further stimuli. Using the ED50 and the first three stimuli as control, the effects of morphine (10 nmol/l-l mmol/l), D-Ala2-MePhe4-Met enkephalin-(O5)-ol (DAMME; 10 nmol/l-0.1 mmol/l) and naloxone (10 nmol/l-10 mumol/l) on the response to the next three stimuli were compared. Morphine, DAMME or naloxone did not significantly alter the amount of catecholamine released by this form of stimulation. Therefore in the rat, under the conditions used, there is no evidence for mu (mu) or delta (delta) opiate modulation of neurally mediated catecholamine release from the rat adrenal medulla. PMID- 2878057 TI - Somatostatin tonically inhibits growth hormone secretion in domestic fowl. AB - Passive immunization of immature chickens with sheep somatostatin (SRIF) antiserum promptly increased the basal plasma GH concentration and augmented TRH induced GH secretion. Although exogenous SRIF had no inhibitory effect on the basal GH concentration in untreated birds or birds pretreated with non-immune sheep serum, it suppressed the stimulatory effect of SRIF immunoneutralization on GH secretion. These results suggest that SRIF is physiologically involved in the control of GH secretion in birds, in which it appears to inhibit GH release tonically. PMID- 2878058 TI - Transcriptional organization of bovine papillomavirus type 4. AB - Seven virus-specific RNA transcripts have been identified in tumours induced by bovine papillomavirus type 4 (BPV-4). The RNAs measured 4.2, 3.6, 3.0, 2.8, 1.9, 1.6 and 1.0 kilobases (kb). They were mapped on the viral genome by Northern blot hybridization to subgenomic probes, by cDNA hybridization to viral DNA fragments and by S1 analysis of unlabelled and 3' and 5' end-labelled DNA fragments. All the RNA species are transcribed from the same DNA strand, are polyadenylated and with the exception of the 1.0 kb RNA internally spliced. The 3.0, 1.9, 1.6 and 1.0 kb RNAs share the same 3' polyadenylation site at nucleotide 4009 whereas the 4.2 kb RNA and the 2.8 kb RNAs terminate near a polyadenylation site at nucleotide 7187. The 4.2 kb and the 2.8 kb RNAs are transcribed from the late open reading frames and encode the structural polypeptides; the 3.0, 1.9, 1.6 and 1.0 kb RNAs are transcribed from the early open reading frames and are the transcripts involved in viral replication and cellular transformation. PMID- 2878059 TI - Complete sequence of the major nucleocapsid protein gene of human parainfluenza type 3 virus: comparison with other negative strand viruses. AB - The sequence of the major nucleocapsid protein (NP) mRNA and its encoded protein were deduced by sequencing a cDNA clone representing the complete mRNA. The cDNA sequence was confirmed by dideoxynucleotide sequencing of purified viral genomic RNA by primer extension using synthetic oligonucleotides. The NP mRNA contains 1,641 nucleotides exclusive of poly(A) and encodes an NP protein of 515 amino acids. Alignment of the human parainfluenza type 3 virus (PF3) NP protein sequence with that of Sendai virus showed that the two proteins shared considerable sequence identity (58.8%). Additional comparisons provided highly significant statistical evidence that the PF3 NP protein sequence is related to those of measles and canine distemper viruses, but there was no evidence of relatedness with the nucleocapsid proteins of respiratory syncytial virus, influenza B virus, or vesicular stomatitis virus. PMID- 2878060 TI - Significance of postnatal mother-to-child transmission of human T-lymphotropic virus type-I on the development of adult T-cell leukemia/lymphoma. AB - In order to shed light on the mode of HTLV-I infection by mother-to-child transmission, we examined sera of school children in a highly endemic town on two separate occasions at a 6-year interval. The carrier rates in ages 15-17, 8.7 and 2.1%, were significantly higher than that in ages 6-8, 1.7 and 0.4%, in studies. The latter survey showed a significantly lower carrier rate in each age group. Moreover, the carrier rates of those students born in 1965-1967 and 1968-1970 were stable in the interval. The data suggested that carrier rates of children at certain ages are reflected by the date of birth rather than by age. A prospective survey of children born of carrier mothers found the overall carrier rate to be approximately 25%, which did not increase with their age. There was no sexual difference in the carrier rate of children: 5/25 in male and 9/34 in females (X2 = 0.3). Carrier mothers could be separated into two groups: HTLV-I antigen positive mothers and negative mothers. Nine out of 19 antigen-positive mothers (47%) and 2 of 19 antigen-negative mothers (11%) had carrier children (X2 = 6.3). Twelve of 30 children born of antigen-positive carrier mothers (40%) were carriers, in contrast to 2 of 24 children (8%) of antigen-negative mothers (X2 = 7.8). Furthermore, 12 of 14 carrier children (86%) were of antigen-positive mothers. This suggests that postnatal but early transmission of HTLV-I plays a significant role in the maintenance of HTLV-I endemy and the development of adult T-cell leukemia/lymphoma. PMID- 2878061 TI - Increases in dopamine utilization in certain limbic dopamine terminal populations after a short period of intermittent exposure of male rats to cigarette smoke. AB - By means of a Walton smoke machine male rats were exposed to cigarette smoke from 1 to 4 cigarettes. Dopamine (DA) levels and utilization in the telencephalon were measured by quantitative histofluorimetry in discrete DA nerve terminal systems of the neostriatum, nucleus accumbens and tuberculum olfactorium. Exposure to unfiltered but not to filtered (Cambridge glass fibre filter) cigarette smoke resulted in a dose-dependent increase in DA utilization in the diffuse types of DA nerve terminal systems in the anterior nucleus accumbens and the lateral posterior tuberculum olfactorium. After exposure to the smoke from 4 cigarettes also an increase in DA utilization was observed in the dotted type (also cholecystokinin [CCK] positive) of DA nerve terminals of the nucleus accumbens (posterior part). The DA utilization in various parts of the neostriatum and in the dotted type of DA nerve terminals in the medial posterior tuberculum olfactorium were unaffected by acute intermittent exposure to cigarette smoke. The DA levels in the various DA nerve terminal systems in neostriatum, nucleus accumbens and tuberculum olfactorium were unaffected with the exception of the dotted and CCK positive type of DA nerve terminals of the nucleus accumbens, where a small reduction of the DA stores was shown following acute intermittent exposure to smoke from 4 cigarettes. The effects induced by exposure to the cigarette smoke in the limbic DA terminals were counteracted by mecamylamine pretreatment. It is suggested that the nicotine component of the cigarette smoke via activation of nicotinic cholinergic receptors can enhance DA release in discrete DA nerve terminal systems of the nucleus accumbens and tuberculum olfactorium. These actions may at least in part mediate the euphoria induced by inhalation of cigarette smoke. PMID- 2878062 TI - The pharmacological management of chronic pain in the paraplegic patient. PMID- 2878063 TI - New taxanes from Taxus brevifolia, 2. PMID- 2878064 TI - The choice of an initial antihypertensive agent. AB - With the current availability of a plethora not only of blood pressure-lowering medications but also of classes thereof and the concern that the long-term use of some of these may result in adverse effects which may offset their benefits has come the recognition of the importance of the choice of an initial antihypertensive agent. Indeed, the initially chosen medication will often be taken for the longest time. The purpose of this review is to consider nine of the major factors permitting a rational choice of medication: antihypertensive efficacy, mechanism of action, safety, patient acceptance (quality of life), cost, numbers of doses per day, need for laboratory follow-up, potential interactions with other drugs, and additional salutary effects. The question of the role of nondiuretic monotherapy is, of necessity, an integral component of this discussion. Preliminary data indicate that the use of this approach with some of the newer agents, including converting enzyme inhibitors and calcium channel blockers, constitutes excellent therapy, at least in certain patients. Finally, because one of the new approaches to antihypertensive therapy is comprehensive risk management, the effect of medication on the lipid profile is considered in some detail. PMID- 2878065 TI - Comparative tolerability of labetalol versus propranolol, atenolol, pindolol, metoprolol, and nadolol. AB - The side-effect profile of labetalol was assessed in 34 patients with mild to moderate essential hypertension who had previously experienced side effects during beta-blocker therapy. The most frequently reported beta-blocker side effects were fatigue, impotence, cold extremities, and depression. After discontinuing their previous beta-blocker for 4 weeks, labetalol was titrated (100-400 mg b.i.d.) to achieve blood pressure control. Twenty-seven of 34 patients did not have a recurrence of a beta-blocker related side effect while receiving labetalol. The most common new side effect with labetalol was dizziness (3 patients). As judged by the attending physician and the patient, labetalol was better tolerated than conventional beta-blocker therapy in 30 of 34 patients (88%). Twenty-four of 34 patients (71%) preferred labetalol over previous therapy. Labetalol controlled blood pressure in 30 of 34 patients (88%). At equal antihypertensive doses, some side effects common to beta-blockers are seen less frequently with labetalol. PMID- 2878066 TI - Imaging of medullary thyroid carcinoma and hyperfunctioning adrenal medulla using iodine-131 metaiodobenzylguanidine. AB - Scintigraphy with radiolabeled metaiodobenzylguanidine was performed in a patient with MEN Type IIa having a pheochromocytoma of the right adrenal gland, adrenomedullary hyperplasia of the left adrenal gland and a primary medullary thyroid carcinoma. The scintigraphic findings demonstrate visualization of all the above mentioned pathologies. PMID- 2878067 TI - Restructuring group meetings for effectiveness. AB - As hospital systems become more complex, health administrators spend more of their time facilitating group decision making. To have effective group management and active participation, group members must value a meeting, and the group should be able to address a large number of issues in an efficient manner. In one rapidly expanding health care system, a group meeting was evaluated in relation to the format and the value to group members. The meeting was then reorganized for optimal efficiency and an evaluation of the effect of the restructuring on the group's perception of the meeting was done. PMID- 2878068 TI - Pathogenesis of human primary hypertension: a new approach to the identification of causal factors and to therapy. AB - In chronic renovascular hypertension the amplifier properties of the hypertrophied heart and vessels contribute considerably more to the maintenance of the elevated blood pressure (BP) than the basic underlying cause. This must also occur in chronic primary hypertension. Accordingly, we hypothesized that after reversal of hypertrophy by antihypertensive medication the cause(s) of hypertension should be easier to detect during the redevelopment of hypertension once medication was stopped, than in the chronic phase of the disorder. We have studied three groups of patients with moderate to severe hypertension in whom BP was controlled for (1) 1 month (2) 1 year and (3) 15 months to 5 years. The rate of subsequent redevelopment of hypertension between the series was inversely related to the duration of therapy, which was mostly with beta-blockers and diuretics. Redevelopment of hypertension was slowest after obtaining regression of both vascular hypertrophy and left ventricular hypertrophy (LVH). Preliminary findings suggest that sympathetic overactivity is present during the redevelopment phase in most patients. Our findings have suggested a new therapeutic strategy, where the effectiveness of non-pharmacological methods of controlling BP is enhanced by first causing regression of cardiovascular hypertrophy by drug treatment. Moderate regular exercise has proved to be an effective non-pharmacological antihypertensive method which has now maintained five patients at normal BP for 1 year, following an initial period of drug treatment. PMID- 2878069 TI - The response of plasma catecholamines to the vasodepression caused by beta adrenoceptor antagonists in the spontaneously hypertensive rat. AB - The 15-20% decrease in mean arterial pressure (MAP) seen in conscious spontaneously hypertensive rats (SHR) after the administration of a single dose of the beta-adrenoceptor antagonists atenolol, betaxolol, oxprenolol, pindolol, propranolol or sotalol was not accompanied by an increase in plasma norepinephrine (NE) concentration. In marked contrast, plasma NE concentration increased by 50-75% when MAP was lowered at the same rate, and to the same extent with the vasodilator minoxidil. Atenolol, betaxolol and propranolol significantly suppressed plasma renin activity (PRA), whereas oxprenolol, pindolol and sotalol did not alter PRA significantly. Based on these observations, I conclude that beta-adrenoceptor antagonists impair the normal baroreflexly-mediated increase in plasma NE concentration which occurs in response to a decrease in MAP and this sympatho-inhibitory effect does not require the suppression of renin release. PMID- 2878070 TI - Atrial natriuretic factor in spontaneously hypertensive rats: concentration changes with the progression of hypertension and elevated formation of cyclic GMP. AB - As hypertension developed in spontaneously hypertensive rats (SHR), the plasma concentration of atrial natriuretic factor (ANF) increased whereas its tissue concentration in the atria decreased. These observations suggest that ANF is secreted from the atria in response to hypertension. Atrial natriuretic factor contents in the hypothalamus and pons decreased with ageing in Wistar-Kyoto rats (WKY) but not in SHR. The responses of various SHR tissues to the hypotensive, vasorelaxant and cyclic GMP generating effects of ANF were more pronounced than in corresponding WKY tissues. The number of ANF receptors was reduced without change in the affinity in aortic smooth muscle and adrenals of SHR with established hypertension. These findings suggest that the elevated sensitivity to ANF of blood pressure of SHR can be in part explained by the increased sensitivity to ANF of guanylate cyclase in the vascular wall of SHR. PMID- 2878071 TI - Receptor-mediated model relating anticonvulsant effect to brain levels of camazepam in the presence of its active metabolites. AB - In a displacement test using 3H-diazepam as a radioligand, the in vitro affinities of metabolites of camazepam (CZ) for the benzodiazepine receptors were 1-50 times more potent than that of CZ. In contrast, only three metabolites (temazepam, oxazepam, and hydroxy CZ), as well as CZ itself, exhibited an in vivo affinity parallel to their ability to protect against pentylenetetrazole--induced clonic convulsion in rats. In addition, CZ and these active metabolites displaced the radioligand from their receptor sites in a concentration-dependent saturable manner, indicating the competitive bimolecular interaction of these molecules with their receptors. The percent anticonvulsant effect was a nonlinear, single valued function of the in vivo percent displacement of specific 3H-diazepam binding, independent of these displacers after i.v. dosing; this relationship could be approximated by the Hill equation. On the basis of these findings, a receptor-mediated model, including the Langmuir equation to describe the receptor binding-brain concentration relationship and the Hill equation to accommodate the anticonvulsant effect-receptor binding relationship, was constructed. This model was found to adequately relate the time course values of anticonvulsant effect and of brain levels of CZ and its active metabolites after oral administration. These results demonstrate that CZ and its active metabolites exert anticonvulsant effect by competitive binding to the benzodiazepine receptors. PMID- 2878072 TI - [Peripheral axonic neuropathy during treatment with almitrine bismesylate (Vectarion). Possible role of wasting]. PMID- 2878073 TI - Rapid neuroleptization. PMID- 2878074 TI - Immunology of allergic rhinitis, or a nose for treatment. PMID- 2878075 TI - Bioisosteric prototype design of biaryl imidazolyl and triazolyl competitive histamine H2-receptor antagonists. AB - The structural relationship of the competitive histamine H2-receptor antagonist 3 amino-5-(2-amino-4-pyridyl)-1,2,4-triazole (1) to the agonist histamine and to antagonists of the cimetidine type was explored by the design and synthesis of four series of bioisosterically designed prototypes. Biological data from these series was best interpreted as indicating a similarity between the imidazole moiety of histamine and cimetidine and the 2-amino-4-pyridyl moiety of 1. On the basis of this data, sequential replacement of 2-amino-4-pyridyl by 2 [(dimethylamino)methyl]-5-furyl and 2-guanidino-4-triazolyl moieties led to a structurally more potent series of biaryl histamine H2-receptor antagonists. The best of these, 2-methyl-4-(2-guanidino-4-thiazolyl)imidazole (29, CP-57,361-1) was 120 times more potent as a histamine H2-receptor antagonist than 1. PMID- 2878076 TI - Synthetic 1,4-disubstituted-1,4-dihydro-5H-tetrazol-5-one derivatives of fentanyl: alfentanil (R 39209), a potent, extremely short-acting narcotic analgesic. AB - The synthesis of a series of N-1,4-disubstituted-1,4-dihydro-5H-tetrazol-5-one piperidinyl derivatives of fentanyl, carfentanil, and sufentanil is described. The 1-substituted tetrazolinones 2 were essentially prepared via the addition reaction of aluminium azide to isocyanates or acid chlorides in tetrahydrofuran. Alkylation of 2 under neutral or weakly basic conditions afforded almost exclusively the 1,4-disubstituted tetrazolinone isomer 3. N-Alkylation of the piperidine derivatives 4 with 3 in dimethylformamide yielded 9a-v. The morphinomimetic activity in rats, after intravenous injection of the compounds, was evaluated in the tail withdrawal reflex test. The fentanyl analogues 9a-c (R4 = H) are inactive at the measured dose of 2.5 or 10 mg/kg (iv). For the carfentanil analogues (R4 = COOCH3) maximal narcotic activity is found when R1 represents a lower alkyl group (9d-f) or a thienylethyl group (9n). The sufentanil analogues (R4 = CH2OCH3) show the same structure-activity relationship (SAR) profile as the carfentanil derivatives (R4 = COOCH3). The structural requirements for optimal activity are in good agreement with earlier observations in the series of 10-12. From the series the ethyl tetrazolinone derivative 9r, alfentanil (R 39209), was selected for clinical investigation. As an analgesic in rats, 9r is 140 times more potent than pethidine 15 and 72 times more potent than morphine 14. Alftentanil reaches its peak effect within 1 min after injection, and its duration of action is very short; at 2 times its MED50, 9r has a duration of action of 11 min. This duration is 30 min for 10 and 90 min for 14. Compared to 10, alfentanil 9r is about 4 times faster but 3 times shorter acting. Structurally, 9r shows most resemblance to sufentanil 12, since it differs only by substitution of a 4-ethyltetrazolinone ring for the thiophene ring. The considerable differences in their pharmacological profiles were explained in terms of marked variations in physicochemical and, hence, pharmacokinetic properties. PMID- 2878077 TI - Synthesis and renal vasodilator activity of some dopamine agonist 1-aryl-2,3,4,5 tetrahydro-1H-3-benzazepine-7,8-diols: halogen and methyl analogues of fenoldopam. AB - Certain 6-halo-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines were found to be potent D-1 dopamine agonists. The 1-(4-hydroxyphenyl) analogues did not have central nervous system activity because their high polarity inhibited entry into the brain. However, these compounds were potent renal vasodilators. Fenoldopam, the 6-chloro analogue, is an especially significant member of the series, and its synthesis, pharmacology, and clinical properties have been studied extensively. The 6-methyl and 6-iodo congeners were potent renal vasodilators, but nonpotent partial D-1 agonists as measured by stimulation of rat caudate adenylate cyclase. A possible rationalization suggests different receptor reserves for these activities. The 9-substituted benzazepines were either inactive or of low potency as dopamine agonists, while the N-methyl analogues had significant antagonist potency as measured by inhibition of dopamine stimulation of rat caudate adenylate cyclase. PMID- 2878078 TI - Synthesis and antiallergic activity of a novel series of 5-lipoxygenase inhibitors. AB - A series of novel substituted [[(phenoxymethyl)phenyl]amino]oxoalkanoic acid esters have been synthesized. These compounds were tested in vitro for their ability to inhibit the synthesis of 5-hydroxyeicosatetraenoic acid and leukotriene (LT) B4 from rat polymorphonuclear leukocytes (PMN) and in vivo as inhibitors ovalbumin- (OA) and LTD4-induced bronchospasm in the guinea pig. Compounds 5-12 and 25 had IC50's between 1 and 5.6 microM in the rat PMN 5 lipoxygenase assay. Compounds 1, 3, and 16 inhibited OA-induced bronchoconstriction (61%, 64%, and 57%, respectively), but only 1 showed activity against LTD4-induced bronchoconstriction. When tested against LTD4-induced contraction of isolated guinea pig tracheal spiral strips, 1 was a competitive inhibitor with a pKB of 4.94. PMID- 2878079 TI - Design and synthesis of conformationally constrained somatostatin analogues with high potency and specificity for mu opioid receptors. AB - A series of cyclic, conformationally constrained peptides related to somatostatin were designed and synthesized in an effort to develop highly selective and potent peptides for the mu opioid receptor. The following new peptides were prepared and tested for their mu opioid receptor potency and selectively in rat brain binding assays: D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (2, CTOP); D-Phe-Cys-Tyr-D-Trp Arg-Thr-Pen-Thr-NH2 (3, CTAP); D-Phe-Cys-Tyr-D-Trp-Nle-Thr-Pen-Thr-NH2 (4); D-Phe Cys-Tyr-D-Trp-Lys-Val-Pen-Thr-NH2 (5); D-Phe-Cys-Tyr-D-Trp-Lys-Gly-Pen-Thr-NH2 (6); D-Phe-Cys-Tyr-Trp-Lys-Thr-Pen-Thr-NH2 (7); D-Tyr-Cys-Tyr-D-Trp-Lys-Thr-Cys Thr-OH (8); D-PhGly-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (9); and D-PhGly-Pen-Phe-D Trp-Lys-Thr-Cys-Thr-OH (10). The most selective peptide, 2 (CTOP), displayed both high affinity (IC50 = 3.5 nM) and exceptional selectivity (IC50 delta/IC50 mu = 4,000) for mu opioid receptors. Furthermore, 2 exhibited very low affinity for somatostatin receptors in the rat brain (IC50 greater than 24,000 nM), with an IC50 somatostatin/IC50 mu receptor selectivity of 8,750. These conformationally constrained cyclic peptides should provide new insight into the structural and conformational requirements for the mu opioid receptor and the physiological role of this receptor. PMID- 2878081 TI - Chemically stable homocinnamyl analogues of the leukotrienes: synthesis and preliminary biological evaluation. AB - The synthesis and biological characterization of a series of stable leukotriene analogues (2) are reported. They are derivatives of (5S,6R,7Z)-6-peptidyl-5 hydroxy-9-phenyl-7-nonenoic acid, in which the phenyl group is variously substituted with a heptanyl, 2-heptenyl, or hexanyloxy chain (R1) and the peptide is either glutathionyl, cysteinylglycinyl, or cysteinyl. The most potent agonist is (5S,6R,7Z)-6-S-glutathionyl-5-hydroxy-9-(4-heptanylphenyl)-7 -nonenoic acid. This analogue has an EC50 value of 74.5 nM, in the presence of 1-serine borate (45 mM), on guinea pig tracheal spirals. The agonist activity of the cysteinylglycinyl- and the cysteinyl-substituted analogues was inhibited by FPL 55712. Three of the analogues were weak leukotriene antagonists in vitro on guinea pig tracheal spirals. The most potent of these was (5S,6R,7Z)-6-S cysteinyl-5-hydroxy-9-(2-heptanylphenyl)-7-++ +nonenoic acid. At 10 microM, this analogue inhibited by 28% the contraction induced by 8 nM LTE4. PMID- 2878080 TI - 6,7-Dichloro-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline . A structurally novel beta-adrenergic receptor blocking agent. AB - Replacement of the catecholic hydroxyl groups of the beta-adrenergic receptor agonist 6,7-dihydroxy-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline (trimetoquinol) with chloro substituents results in a compound with marked beta adrenoceptor antagonist properties. This, therefore, parallels the similar transformation of the beta-adrenoreceptor agonist isoproterenol into the antagonist dichloroisoproterenol. In a test for inhibition of isoproterenol induced enhancement of the rate of contraction of spontaneously beating guinea pig atrial pairs the resultant 6,7-dichloro-1-(3,4,5-trimethoxybenzyl)-1,2,3,4 tetrahydroisoquinoline (6b) had a KB value of (6.7 +/- 2.3) X 10(-8) M. Although this is nearly 2 orders of magnitude less potent than propranolol (KB = 6.2 X 10( 10) M in this test), this compound represents the prototype of a new class of beta-adrenergic receptor blockers, and unlike dichloroisoproterenol it is not a partial agonist. It has physicochemical properties, e.g., pKa and distribution and partition coefficients, that differ from the prototypic beta-blockers. These altered properties might impart advantageous tissue distribution and altered pharmacological properties to the new molecule. This new beta-adrenoreceptor antagonist is suggested to merit further study. PMID- 2878082 TI - A critical appraisal of recent drug research in mental retardation: the Coldwater studies. AB - This paper attempts to assess public and professional attitudes toward drug treatment in mental retardation and concludes that considerable sentiment has developed in recent years against the use of pharmacotherapy. A number of factors contributing to this prevailing attitude were identified and discussed. In particular, a series of investigations carried out by researchers at the Coldwater Regional Center for Developmental Disabilities (Michigan), which have had negative implications for drug treatment, were summarized. These studies have suggested that psychotropic drugs, especially the antipsychotics, may adversely affect clinical management of mentally retarded persons, depress learning performance, and interfere with the efficacy of reinforcement contingencies. However, certain features of these studies, such as the procedures for selecting subjects, the doses utilized and overall guiding philosophy, appear to limit their relevance. Balanced against these are a number of other investigations showing circumscribed positive clinical effects, a lack of interference with learning and little or no disruption of reinforcement contingencies. It was concluded that all-encompassing judgments about the value of pharmacotherapy in mentally retarded people are premature at this time. We suggested that a major objective of clinical drug research should be to look for enhancement of adaptive functioning by discovering appropriate subject-treatment combinations, while remaining vigilant for adverse effects. PMID- 2878083 TI - The effect of glutamate on hypoxic newborn rabbit heart. AB - Effects of glutamate on myocardial mechanical function and energy metabolism during 120 min of hypoxia and subsequent reoxygenation were studied in the isolated arterially perfused newborn and adult rabbit hearts. The muscle was perfused with a Krebs-Henseleit (KH) solution or KH solution which contained 1 mM glutamate. Glutamate attenuated the effects of hypoxia on mechanical function and tissue ATP concentration, and enhanced the recovery of mechanical function and tissue ATP during reoxygenation. During hypoxia, glutamate increased tissue succinate and GTP with no change in total lactate and pyruvate production. Trace studies using 14C-glutamate and the tissue homogenate showed that hypoxia increased tissue succinate and inhibited TCA cycle. Additional glutamate produced more CO2 and TCA intermediates in both oxygenated and hypoxic mediums. These data indicate that glutamate increased the rate of ATP production in the hypoxic and reoxygenated heart. This study shows that the improvement of mechanical function and ATP formation in the hypoxic myocardium by glutamate was due to an increase in both oxidative phosphorylation and substrate level phosphorylation. The effect of glutamate on the ATP and GTP production in the newborn heart was not different from the adult. PMID- 2878084 TI - Infarct size pharmacology--where next? PMID- 2878085 TI - Beta blockers and infarct size. AB - Reduction of myocardial oxygen demand by beta blockers should be beneficial for treatment of the supply-demand imbalance of severe myocardial ischaemia leading to infarction. There is evidence that rate-pressure product, an index of myocardial oxygen demand, is an independent variable for determination of infarct size, and that reduction of rate-pressure product by beta blockers or by other means is beneficial. Although experimental evidence is conflicting, some animal studies have shown protection from beta blockers when a coronary artery is permanently occluded, while a majority of studies show protection when a temporary coronary artery occlusion is followed by reperfusion. Prevention of ventricular fibrillation due to coronary artery occlusion has been shown in animal studies. In patients with developing infarction, rate-pressure product is reduced by approximately 20% when a beta blocker is given intravenously, and cardiac metabolism, assessed by coronary sinus sampling, returns to a more normal "oxidative" pattern. Indirect indices of infarct size, namely serum enzyme release and precordial R wave loss are reduced in patients treated early with intravenous beta blockers compared with control patients. However there is no evidence that left ventricular function is preserved by beta blockers. Very large multicentre trials have shown reduction in mortality among treated patients by about 15% when an intravenous beta blocker is given, suggesting that routine use would save 1 life for every 100-200 patients treated. PMID- 2878086 TI - Beta blockers, hypertension, and blacks--is the answer really in? AB - It has been reported that beta blockers are not effective antihypertensives in black populations. A review of the literature revealed that, for the most part, studies drawing this conclusion were of small sample size, lacked controls, and did not represent the demographics of the US black population. The largest US study (Veterans Administration Cooperative Study) showed propranolol to be effective in at least one half of the black patients, with white patients responding better, but diuretics were more effective in both races. More recent studies show beta blockers with alpha-antagonistic properties to be effective in black hypertensives. The question is raised whether enough data have been analyzed to suggest these drugs are ineffective for black hypertensives. PMID- 2878087 TI - Factor XIII as a modulator of plasma fibronectin alterations during experimental bacteremia. AB - Fibronectin is found in plasma as well as in association with connective tissue and cell surfaces. Depletion of plasma fibronectin is often observed in septic trauma and burned patients, while experimental rats often manifest hyperfibronectinemia with sepsis. Since Factor XIII may influence the rate of clearance and deposition of plasma fibronectin into tissues, we evaluated the temporal changes in plasma fibronectin and plasma Factor XIII following bacteremia and RE blockade in rats in an attempt to understand the mechanism leading to elevation of fibronectin levels in bacteremic rats, which is distinct from that observed with RE blockade. Clearance of exogenously administered fibronectin after bacteremia was also determined. Rats received either saline, Pseudomonas aeruginosa (1 X 10(9) organisms), gelatinized RE test lipid emulsion (50 mg/100 gm B.W.), or emulsion followed by Pseudomonas. Plasma fibronectin and Factor XIII were determined at 0, 2, 24, and 48 hours post-blockade or bacteremia. At 24 and 48 hr following bacteremia alone or bacteremia after RE blockade, there was a significant elevation (p less than 0.05) of plasma fibronectin and a concomitant decrease (p less than 0.05) of plasma factor XIII activity. Extractable tissue fibronectin from liver and spleen was also increased at 24 and 48 hours following R.E. blockade plus bacteremia. In addition, the plasma clearance of human fibronectin was significantly prolonged (p less than 0.05) following bacterial challenge. Infusion of activated Factor XIII (20 units/rat) during a period of hyperfibronectinemia (908.0 +/- 55.1 micrograms/ml) resulted in a significant (p less than 0.05) decrease in plasma fibronectin (548.5 +/- 49.9 micrograms/ml) within 30 min. Thus Factor XIII deficiency in rats with bacteremia may contribute to the elevation in plasma fibronectin by altering kinetics associated with the clearance of fibronectin from the blood. PMID- 2878088 TI - Reversal of postburn immunosuppression with low-dose polymyxin B. AB - In a randomized study of 28 patients with thermal injury, polymyxin B was administered intravenously in small doses to attempt to block the immunosuppressive effects of endotoxin. When compared with controls, treated patients showed a reduction in septic complications and death, but this reduction is not statistically significant at this time. In vitro measurements of lymphocyte function, however, indicate a statistically significant improvement in the T helper to suppressor ratio, and in the lymphocyte responsiveness to a number of bacterial antigens. PMID- 2878089 TI - Annulate lamellae and single-pore complexes in human spermatogonia. AB - Electron microscopic examination of non-neoplastic human testes revealed cytoplasmic annulate lamellae (AL) in all cell types within the seminiferous epithelium. Short lamellar profiles with low numbers of pores were found in spermatogonia and spermatocytes, while larger stacks of AL were seen in spermatids and Sertoli cells. Stacks of lamellae were closely associated with redundant nuclear envelope during late spermiogenesis. Residual bodies shed by the developing spermatozoa contained large number of lamellar-pore complexes. One cryptorchid testis was also examined. In this case the seminiferous epithelium consisted only of Sertoli cells with rare spermatogonia. AL were found in both cell types, with a similar morphology to those of the non-neoplastic testes. This study demonstrates that AL are expressed in all stages of spermatogenesis. PMID- 2878090 TI - A preferred region for integration of Friend murine leukemia virus in hematopoietic neoplasms is closely linked to the Int-2 oncogene. AB - Gene mapping experiments show that Fis-1, a preferred integration region for Friend murine leukemia virus in hematopoietic neoplasms, is extremely closely linked to Int-2, a preferred integration region for mouse mammary tumor virus in mammary carcinomas. Studies at the RNA and DNA level prove that these loci are distinct. PMID- 2878091 TI - Chromosomal localization of Emv-16 and Emv-17, two closely linked ecotropic proviruses of RF/J mice. AB - Emv-16 and Emv-17, the two closely linked ecotropic proviral loci of RF/J mice, have been mapped to chromosome 1 between leaden, ln, and the mouse engrailed homeo-box locus, En-1, by using recombinant inbred strains and conventional backcross analysis. PMID- 2878093 TI - Transmission of HTLV-II. PMID- 2878092 TI - Antisera to scrapie-associated fibril protein and prion protein decorate scrapie associated fibrils. AB - Scrapie-associated fibrils (SAF) are an infection-specific structure observed in the unconventional-agent diseases. Polyclonal antisera raised to scrapie proteins were used to test the antigenic relationship between purified fibrils and SAF isolated from non-protease-treated synaptosomal-mitochondrial preparations. The experimental design utilized fibrils from scrapie strain 263K-infected hamsters, scrapie strain 139A-infected mice, and scrapie strain ME7-infected mice. Preparations were examined by negative-stain immune electron microscopy and Western blot analysis of the polypeptides. Fibrils and polypeptides from each preparation reacted with a rabbit antiserum raised to each of the following: hamster 263K prion protein (PrP 27-30), hamster 263K SAF protein, and mouse ME7 SAF protein. Immune electron microscopy and Western blot analysis revealed similar antigenic relationships among the three scrapie antisera. Thus, fibrils and polypeptides can be considered to be the same in each preparation. No reactivity of the fibrils was observed with antisera raised to Alzheimer neurofibrillary tangles or a synthetic peptide of cerebrovascular amyloid. Thus, the fibrils observed in purified preparations share structural and antigenic similarities plus biochemically related peptides with SAF present in non-protease treated preparations. PMID- 2878094 TI - A case of Takayasu's disease with ruptured carotid aneurysm. AB - Recently, a number of cases of Takayasu's disease having dilatative or aneurysmal lesions have been reported. Such lesions have come to be considered important manifestations of Takayasu's disease. A case, whose right common carotid artery perforated spontaneously and became a pseudoaneurysm, without any other stenotic lesion is presented with a review of the literature. Surgical treatment was performed successfully. PMID- 2878095 TI - [Nuclear DNA fluorocytophotometric analysis of leukemic cells in adult T-cell leukemia/lymphomas (ATLL)]. AB - The nuclear DNA content of the leukemic cells in six cases of ATLL and one of peripheral T-cell malignant lymphoma (PTML) were analyzed by fluorocytophotometry, simultaneously evaluating the nuclear shape and the longest nuclear axis (LNA). The leukemic cells, characterized by the nuclear shape and LNA, had a little hyperdiploid DNA content, and they belonged to GO/GI cells. The life span of the leukemic cells was suggested to be as short as two to three weeks or much longer than the survival time of the patients, evaluating the change of the LNA histogram under chemotherapy from the diagnosis up to the patients' death. One of the ATLLs, showing small leukemic cells and a clinical course of more than three years, might be a new entity, T-CLL-like ATLL. PMID- 2878096 TI - [The differential effect of dynorphin on dopamine and GABA uptake in cerebral ischemia]. PMID- 2878097 TI - [Measurement of blood flow volume of the ocular muscles by the Xe-133 clearance method]. PMID- 2878099 TI - Cholinergic modulation and effects of dynorphin on the non-adrenergic inhibitory potentials in the guinea-pig duodenum. AB - Cholinergic modulation and effects of dynorphin on the non-adrenergic non cholinergic inhibitory potentials (NANC i.p.s) in the longitudinal smooth muscle cells of the guinea-pig duodenum were studied intracellularly. Atropine (1.4 X 10(-7)-1.4 X 10(-5) M) and scopolamine (3.3 X 10(-8)-3.3 X 10(-7) M) increased the amplitude of the evoked i.p.s while physostigmine (3.7 X 10(-7)-3.7 X 10(-6) M) and neostigmine (4.8 X 10(-8) M) decreased it. The frequency of the spontaneous action potentials in the longitudinal smooth muscle cells was increased by dynorphin (6 X 10(-8)-3 X 10(-7) M) without continuous membrane depolarization. The excitatory effect of dynorphin on the spontaneous electrical activity was not blocked by atropine (1.4 X 10(-6) M). Dynorphin (6 X 10(-8)-2.4 X 10(-7) M) increased the amplitude of the i.p.s evoked in the presence of atropine (1.4 X 10(-7)-1.4 X 10(-6) M) and in the propranolol (3.9 X 10(-6) M) solution containing atropine while dynorphin decreased the amplitude of the i.p.s evoked in the absence of atropine. In the high calcium solution containing atropine, the amplitude of the i.p.s increased. Further increase in the amplitude of the i.p.s was observed by additively applied dynorphin. However, the amplitude of the i.p.s evoked in the high calcium solution without atropine was decreased by dynorphin. These results suggest the cholinergic inhibitory modulation on the NANC inhibitory nerves in the guinea-pig duodenum, the non-cholinergic excitatory action of dynorphin on the spontaneous electrical activity of the longitudinal smooth muscle and the excitatory action of dynorphin on the NANC inhibitory nerves in the presence of muscarinic blocking agents. PMID- 2878098 TI - Responses of arcuate neurons to some putative neurotransmitters in perfused rat hypothalamic slices: effects of in vivo and in vitro estrogen treatments. AB - The responses of neurons in the arcuate nucleus (ARC) to gamma-aminobutyric acid (GABA), glycine, serotonin (5-HT), norepinephrine (NE), and dopamine (DA) were examined in hypothalamic slices from ovariectomized rats either treated or untreated with estrogen. In estrogen-untreated preparations, spontaneous unit activity of the majority of neurons identified antidromically by the median eminence (ME) stimulation was depressed by GABA and glycine. When effective, 5-HT was predominantly excitatory and DA was predominantly inhibitory, while NE evoked both excitatory and inhibitory responses. The IS-SD block in evoked spikes was also occasionally observed following GABA and glycine perfusion. The responsiveness of unidentified neurons, which were not activated by the ME stimulation, to agents other than 5-HT did not differ from that of antidromically identified neurons. Responses of unidentified neurons to 5-HT were predominantly inhibitory. Subcutaneous injection of 20 micrograms of 17 beta-estradiol-benzoate 2 days prior to the experiments did not significantly affect the responsiveness of both identified and unidentified neurons to GABA, 5-HT, DA, and NE. Contrarily, preincubation of slices in 17 beta-estradiol-containing medium (10 nM) for 1 h significantly increased the responsiveness of unidentified, but not identified, neurons to the inhibitory action of NE. These results suggest that GABA, glycine, 5-HT, NE, and DA play some functional roles in controlling the excitability of tuberoinfundibular (TI) neurons in the ARC. It is also suggested that the negative feedback effect of estrogen is mediated, at least in part, by increased responsiveness of ARC neurons other than TI neurons to the inhibitory action of NE. PMID- 2878100 TI - Possible involvement of ganglionic blocking effects of diltiazem in regulation of blood pressure and heart rate of the rabbit. AB - Under pentobarbitone anesthesia, arterial blood pressure and heart rate were recorded in rabbits. The elevation in systemic blood pressure and increased heart rate induced by electrical stimulation of the right thoracic sympathetic nerve trunk were depressed by either an intravenous injection of diltiazem (300 micrograms/kg) or by placing cotton pledgets soaked in 2 mM diltiazem solution onto the right stellate ganglion. These inhibiting effects of diltiazem were statistically significant with high sympathetic stimulation frequencies (10-20 Hz), but not when lower frequencies (1-5 Hz) were used. On the other hand, hexamethonium (10 mg/kg i.v. or 100 mM applied topically) depressed cardiovascular responses to sympathetic stimulation over a wide range of frequencies (1-20 Hz). Present results reveal a frequency-dependent inhibition of ganglionic transmission by diltiazem, and suggest that diltiazem may depress excessive sympathetic activity without affecting normal ganglionic transmission. PMID- 2878101 TI - Effects of adrenoceptor agonists and antagonists on the firing of neurons in the rat A1 noradrenergic region. AB - Noradrenaline (NA), but not clonidine applied microiontophoretically, inhibited the firing of neurons in the rat A1 noradrenergic region, whereas intravenous clonidine dose-dependently inhibited their firing (ED50 = 18.3 micrograms/kg). The NA-induced inhibition was blocked by the beta-antagonist timolol, but not by the alpha-antagonists phentolamine or piperoxane. These results suggest that neurons in the A1 region possess beta-adrenoceptors rather than alpha adrenoceptors near their cell bodies, and that systemically administered clonidine acts indirectly on these cells. PMID- 2878102 TI - [Contractile function of the myocardium and central hemodynamics in acute myocardial infarct patients after a single intravenous injection of adrenergic beta receptor blockaders]. AB - Cardiac hemodynamics and myocardial contractility were examined in patients with acute myocardial infarction during urgent aorto-coronary shunting with and without beta-adrenergic blockers. The beta-blockers were shown to have a protective effect, as reflected in a smaller myocardial strain owing to a decrease in heart rate, stroke and cardiac outputs, and pulmonary arterial blood pressure. Propranolol proved the most effective agent, whereas visken produced the smallest effect. PMID- 2878103 TI - [Current locally acting agents in the treatment of peptic ulcer]. PMID- 2878104 TI - [Pancreatic incretory function in the hypothalamic puberty syndrome]. PMID- 2878105 TI - [Endorphin-, gastrin- and somatostatin-containing cells in the mucosa of the stomach and duodenum in duodenal ulcer and chronic gastritis]. PMID- 2878106 TI - [Chemical sensitivity of the neurons of the medial vestibular nucleus to enkephalins, acetylcholine, GABA and L-glutamate]. AB - The effect of enkephalins, morphine and some neurotransmitters on spontaneous and evoked activity of neurons of the medial vestibular nucleus was investigated. The evoked activity was produced by an adequate stimulation of the vestibular apparatus. It was shown that neurons of this nucleus were highly sensitive to enkephalins, morphine, acetyl choline, GABA and L-glutamate (approximately 80% of the nerve cells were inhibited or excited in response to the micro-iontophoretic application of these substances). It was found that activation and depression effects of opioid peptides and morphine occurred due to the stimulation of mu- and delta-opiate receptors. It can be concluded that enkephalins modulate cholinergic and glutamatergic synaptic transfer in the medial vestibular nucleus. Together with opiate receptors, they participate in the perception and processing of vestibular information at the level of neurons of this nucleus. PMID- 2878107 TI - [Functional evaluation of the musculoskeletal system under an autonomous life support regimen based on data on blood biochemical indices]. AB - The functional state of the musculo-skeletal system of healthy male volunteers of three age groups (Group 1--19-21 years, n = 16; Group 2--25-43 years, n = 26; Group 3--48-59 years, n = 30) was evaluated. The subjects were kept in an enclosure for 30 days. Creatine phosphokinase (CPK), lactate dehydrogenase (LDH), alkaline phosphatase, aspartate aminotransferase (AAT), calcium, P1 were measured in blood. The test subjects of the three groups showed a decrease of CPK, LDH, AAT and creatinine. The correlation coefficient between the enzymes varied from 0.64 to 1.00. By the end of the study alkaline phosphatase increased in the Group 1 and 2 subjects and decreased in the Group 3 subjects. Calcium variations were less distinct. The Pi content declined significantly in the Group 3 subjects. Some of the Group 3 subjects who performed regular exercises during the study exhibited smaller decreases of CPK, LDH, AAT and greater stability of calcium and phosphorus. PMID- 2878108 TI - [Reasons for the formation of hydrogen sulfide in regenerated water]. AB - The factors responsible for the formation of hydrogen sulphide in the water reclaimed from the atmospheric condensate were investigated. It was found that hydrogen sulphide developed in reclaimed water due to microorganisms which in the presence of inorganic sulphur (sodium thiosulphate) acquired the capacity to produce hydrogen sulphide, although normally they are not sulphur reducing. Among the microorganisms studied, E. coli showed the highest capacity (100%) and Streptococcus faecalis and Citrobacter freundii showed the lowest capacity (10 20%) to produce hydrogen sulphide. PMID- 2878109 TI - [Characteristics of the formation of a microbial complex in the nutrient solutions of higher plants after the use of straw mineralization products]. AB - The effect of a product of wheat straw mineralization, e. g. ecothole, on the formation of a microbial complex that is concomitant with lettuce plants during 7 vegetations (i. e. 189 days) was investigated. The plants were grown by the subirrigation-aeroponic method on nutrient solutions that were not replaced throughout the study. It was found that in the course of lettuce ontogenesis the count of microorganisms, fungi and actinomycetes varied in the range 10(5) to 10(6), 10(2) to 10(4) and 10(2) to 10(5) cells per ml solution, respectively. During all lettuce vegetations 19 bacterial species were isolated. During the first vegetation a stable microbial complex with predominant gram-negative bacteria developed. However, addition of ecothole caused an increase in the count of spore-forming bacteria, whereas in the control the count of nitrogen-fixing bacteria grew. PMID- 2878110 TI - [Biochemical aspects of the functioning of neurohumoral systems in long-term head down tilt hypokinesia]. PMID- 2878111 TI - Brain amino acid abnormalities in pyruvate carboxylase deficiency. AB - Amino acids were measured in several regions of autopsied brain from an infant who died with congenital lactic acidosis due to pyruvate carboxylase deficiency (McKusick 26615), as well as in cerebrospinal fluid (CSF) and plasma of four living infants with this disorder. Glutamine content was greatly reduced in all brain regions, while glutamic acid and proline contents were elevated. The gamma aminobutyric acid (GABA) content was normal in brain. Glutamine concentrations in CSF and plasma were also decreased in the living patients. Glutamine may serve as a pool to provide glutamate and GABA for use as neurotransmitters, and to provide alpha-ketoglutarate for the tricarboxylic acid cycle when oxaloacetate can no longer be formed directly from pyruvate. PMID- 2878112 TI - Lipid metabolism in biotin-responsive multiple carboxylase deficiency. PMID- 2878113 TI - Direct DNA analysis in family studies. AB - Restriction fragment length polymorphisms can be followed through families to track the incidence of genetic disease. Either cloned genes or anonymous DNA fragments, closely linked to the disease locus, may be used. 10 mL of blood collected into EDTA provide an excellent source of DNA and the blood is suitable for up to 3 days. In addition to gene tracking, the gene mutation itself may be studied to determine whether there is a DNA deletion. PMID- 2878114 TI - Applications and limitations of direct DNA analysis in genetic prediction. AB - Direct analysis of DNA has enormous potential for improved carrier detection or exclusion and early prenatal diagnosis in monogenic diseases. The strategy adopted in practice is determined by the fact that in most diseases allelic genetic heterogeneity precludes elucidation of the mutation in all families. Gene tracking asks the question--has a relative or fetus inherited the same relevant chromosome region as a previously affected family member?--and requires a gene specific or closely linked DNA probe that reveals a restriction fragment length polymorphism (RFLP) in order to do a linkage study within the family. Gene tracking is independent of allelic heterogeneity in the disease, but is limited to those families in which key relatives are heterozygous for an RFLP. PMID- 2878115 TI - DNA analysis for ornithine transcarbamylase deficiency. AB - We have utilized the Southern blotting technique to analyse genomic DNA from males with ornithine transcarbamylase (OTC) deficiency and their families. Using a nearly full-length human cDNA probe, we have identified 3 patients with deletions at this locus and have characterized 4 different restriction fragment length polymorphisms that can be used as linkage markers for the OTC mutation. These polymorphisms occur at sufficiently high frequencies so as to enable us to distinguish the two X-chromosomes in approximately 80% of OTC carriers. As a direct consequence of these findings, prenatal diagnosis and carrier assessment can be offered to a large fraction of families at risk for OTC deficiency. PMID- 2878116 TI - Molecular genetics of PKU. PMID- 2878117 TI - Diabetes mellitus, atherosclerosis, and the 5' flanking polymorphism of the human insulin gene. AB - On the 5' side of the human insulin gene is a highly polymorphic locus containing 2 major size classes of DNA restriction fragments which segregate in families as stable genetic elements. Fragments with an average size of about 600 base-pairs (bp) (the 'L-allele') seem to be a weak genetic marker for type 1 (insulin dependent) diabetes mellitus, whereas fragments of an average size of about 2500 bp (the 'U-allele') have hitherto been associated with type 2 (non-insulin dependent) diabetes mellitus and diabetic hypertriglyceridaemia. Recent evidence does not confirm the association between the U-allele and type 2 diabetes. Our own studies suggest that the U-allele is a fairly strong marker for the development of atherosclerosis with a relative risk for U-carriers of 3.36. The U allele has not been associated with conventional cardiovascular risk factors such as body weight, blood pressure, or levels of blood glucose, triglycerides or lipoproteins. The putative functions of the polymorphic region in the aetiology of type 1 diabetes and atherosclerosis, and the relation of this region to other genetic markers for these disorders are not known. PMID- 2878119 TI - On the quantal hypothesis of neurotransmitter release: an explanation for the calcium dependence of the binomial parameters. AB - Results for quantal neurotransmitter release can be explained by assuming a binomial distribution with a population of N elements each with a probability p to release a quantum in a given trial. The binomial parameter N was unexpectedly observed to depend on external calcium concentration and (to a lesser extent) on the frequency of stimulation. This observation is explained here by the hypothesis that the release population is not homogeneous. It is shown that the same hypothesis can also account for other experimental findings. A possible cause for this inhomogeneity is suggested. PMID- 2878118 TI - Liquid chromatographic separation of enantiomers of adrenergic agonists. AB - Many established and experimental adrenergic agonists are derivatives of 2 aminoethanol with a phenol or catechol moiety in the 1-position. There is considerable interest in the stereochemical aspects of the actions of such chiral drugs. Surprisingly, however, little has been published on the chromatographic separation of the enantiomers of these compounds, and what has been published involved nearly exclusively capillary gas-liquid chromatography. In this report, the resolution of the racemates of ten adrenergic agents using reversed-phase liquid chromatography is described. The procedure is based on derivatizing the racemic mixture of each agent with the chiral reagent 2,3,4,6-tetra-O-acetyl-beta D-glucopyranosyl isothiocyanate, followed by separation of the resulting diastereomers on octadecylsilane columns using methanol-aqueous ammonium acetate mixtures as mobile phase. Detection was at 254 nm. The separation of the enantiomers of norphenylephrine and of octopamine was less than complete; the resolution of the other agents, i.e., synephrine, N-ethylnorphenylephrine, p hydroxyephedrine, p-hydroxynorephedrine, metanephrine, normetanephrine, isoproterenol, and nordefrin, was complete. The derivative of (-)-isoproterenol eluted before that of its antipode. The procedure may be applicable to other similar agents. PMID- 2878120 TI - Note on an abnormality of the operator for the structural gene of the dopamine D1 receptor as a possible partial cause of schizophrenia. PMID- 2878121 TI - Internal mammary artery grafting. Clinical results, patency rates, and long-term survival in 833 patients. AB - This report reviews 833 patients who underwent internal mammary artery grafting alone or with vein grafts between 1968 and 1981. Use of the internal mammary artery was indicated in young or middle-aged patients with the following characteristics: a significant lesion of the proximal left anterior descending artery or its diagonal branch alone (70.1%) or combined with diffuse atherosclerosis (19.9%) or a small caliber (3.4%); absent or unsuitable veins for grafting (5.5%); atherosclerosis or an aneurysm of the ascending aorta (0.6%); and failure of previous vein grafts (0.5%). The left anterior descending artery system was grafted by the left internal mammary artery in 53.2%, and the arterial graft was complimented by vein grafts in 2.6%. In 45.2% of the patients, grafts of the left anterior descending artery by the left internal mammary artery were supplemented by vein grafts to the right coronary artery (23.8%), to the circumflex artery (15.2%), or to both (6.2%). The overall operative mortality was 2.2%. It rose to 16.7% with associated cardiac procedures and to 18.5% in patients who were in New York Heart Association Class IV. If these two high-risk categories of patients are excluded, the perioperative death rate in the remaining 750 was only 0.4%. Of the 815 patients who survived the perioperative period (mean 53.1 months follow-up), 63.1% were relieved of angina and 83.4% were in Class I or II of the New York Heart Association, as compared to 27.4% before the operation. At cardiac recatheterization (mean 18.9 months), 87.9% of the internal mammary artery grafts and 63.3% of the vein grafts were patent (p less than 0.05). The cumulative actuarial 10 year survival rate was 88.6% +/- 1.3%. PMID- 2878122 TI - Internal mammary artery graft. PMID- 2878123 TI - Human T cell hybridomas producing cytotoxic lymphokines: induction of lymphotoxin release and killer cell activity by anti-CD3 monoclonal antibody or lectins and phorbol ester. AB - Human T cell hybrids were constructed between lectin-activated peripheral blood lymphocytes and CEM.TET1, a variant of the CEM T lymphoblastoid cell line. Hybrids were screened for their ability to produce cytotoxic lymphokines and interleukin-2 (IL-2) following lectin activation. Five hybrids were identified that released significant levels (greater than 75 units/ml) of cytotoxic activity that was detected on the murine L929 target cells; three hybrids were identified that produced IL-2. Cell surface phenotype of the T cell hybrids did not correlate with their ability to produce these lymphokines. The II-23 hybrid (CD3+;4+) produced an inducible cytotoxic activity that was fully neutralized by anti-lymphotoxin antibodies. The release of lymphotoxin (LT) rapidly attained maximum levels 12 hrs to 24 hrs after lectin activation; IL-2 production was maximum at 48 hrs. The induction of LT and IL-2 release required similar membrane stimulating agents. The phorbol ester, phorbol 12-myristate 13-acetate (PMA) in combination with phytohemagglutinin or concanavalin A, were required for maximal release of LT and IL-2. Anti-CD3 monoclonal antibodies coupled to agarose, but not anti-T200-agarose, induced the release of high levels of LT and IL-2. Soluble anti-CD3 was not sufficient to induce IL-2 or LT release from the II-23 hybrid; however, soluble anti-CD3 combined with PMA was a strong stimulus for lymphotoxin and IL-2 release. The II-23 hybrid also functioned as a cytotoxic T cell line in a 51Chromium release assay. Induction of killer cell function required similar perturbation of Ti/CD3 complex. This human T cell hybrid line offers an inducible model system for the simultaneous study of the molecular events regulating the production of growth inhibitory/cytotoxic (LT) and growth promoting (IL-2) lymphokines and cytotoxic T cell function. PMID- 2878124 TI - Effects of T cell growth factor/interleukin II on prothymocytes. AB - The present report describes evidence to show that interleukin 2 (IL-2), in addition to its well known action as a second signal in mitogenic action on mature T cells, functions as a regulator of both proliferation and maturation of immature T lymphocytes. The present experiments extend previous observations indicating that immature thymocytes (Thy1+, L3T4-, Ly2-) are a target of IL-2 action. IL-2 and thymosin fraction V but not interleukin 1 (IL-1) induce differentiation of prothymocytes (Thy1-, L3T4-, Ly2-) obtained from spleens of nude mice as measured by the acquisition of the Thy 1 marker. IL-2, but not thymosin fraction V and IL-1, modulates the proliferation of this cell population. The data indicate that IL-2 may exert a significant regulatory function in T cell ontogeny. PMID- 2878125 TI - Defective IL-2 production in patients with severe burns and sepsis. PMID- 2878126 TI - The hereditary multiple endocrine neoplasia syndrome type 2 in Polish-American family. PMID- 2878127 TI - [Thyroid-stimulating immunoglobulins in Graves disease. Usefulness of a radioreceptor assay]. PMID- 2878128 TI - [Patient-controlled administration of analgesics--an alternative in intensive care]. PMID- 2878129 TI - Serological markers in early stages of human immunodeficiency virus infection in haemophiliacs. AB - Immunoassays for human immunodeficiency virus antigen (HIV Ag) and for antibody to HIV core and envelope (CIA-RA) were done on serial specimens from 40 haemophiliacs who had become seropositive on screening by enzyme-linked immunosorbent assay (ELISA). HIV Ag was detectable in 9 subjects and antibodies to envelope in 11 subjects before ELISA seroconversion. The apparent sequence of markers is HIV Ag, antibody to envelope, then antibody to core. Antigenaemia could be detected as soon as 2 weeks after infection and lasted 3-5 months. 82% agreement was seen between CIA-RA and western blot; CIA was more sensitive to envelope antibody and western blot was more sensitive to core antibody. PMID- 2878130 TI - Principal results of the Medical Research Council's 8th acute myeloid leukaemia trial. AB - Between 1978 and 1983, 1127 patients with de-novo acute myeloid leukaemia (AML) were entered into the Medical Research Council (MRC)'s 8th AML trial. All received the same induction therapy consisting of daunorubicin, cytarabine, and 6 thioguanine--DAT (1 + 5). The 67% who entered complete remission were randomised to consolidation with two or six further courses of DAT. Adults under the age of 55 were randomised for central nervous system (CNS) prophylaxis with intrathecal cytarabine and methotrexate. Finally, those still in remission after 1 year of cytarabine and 6-thioguanine (AT) maintenance were randomised to receive either late intensification with cyclophosphamide, vincristine, cytarabine, and prednisolone (COAP) or continued AT. The median survival for the whole group was 12 months; the median duration of first remission was 15 months, with relapse free survival at 5 years estimated at 18%. The factors most strongly associated with poor survival were performance status and age at presentation, but even among those over 60 years of age, half went into remission. Six courses of DAT consolidation gave a small advantage over two courses in reducing the number of late relapses but no significant survival advantage. Late intensification showed a marginally significant advantage over continued AT maintenance. The incidence of CNS relapse was low and unaffected by prophylaxis. The second remission rate varied from 10% when the first remission was shorter than 6 months to 61% when it had continued for more than 2 years. 40 patients received histocompatible allogeneic bone-marrow transplants in first remission. There was a high procedure related death rate, particularly among patients over 30 years of age. Thus, initially at least, the transplanted group had shorter survival than a comparable group of chemotherapy-treated patients. Treatment specifications remained unchanged throughout the trial but those enrolled in the later half of the trial had a better (p = 0.003) survival. PMID- 2878131 TI - Haemodynamic effects of atrial peptide infusion in heart failure. AB - The effect of a synthetic analogue of atrial natriuretic peptide (Ileu-ANP) on haemodynamic, hormonal, and electrolyte excretion indices was studied in 7 patients with chronic congestive heart failure. Patients received in random order placebo or Ileu-ANP infusions (5 micrograms/min) for 4 h on 2 separate occasions, at least 1 week apart. Compared with placebo, Ileu-ANP caused significant reductions in mean systemic arterial pressure, mean pulmonary artery pressure, pulmonary diastolic pressure, and right atrial pressure. These changes were sustained for at least 2 h after infusion. Cardiac output increased from 6.2 to 7.4 l/min at 60 min, then returned to pre-infusion levels. Despite considerable falls in systemic pressure there was no significant increase in heart rate or plasma noradrenaline. With Ileu-ANP infusion, plasma renin activity, angiotensin, arginine vasopressin, aldosterone, and cortisol values were not significantly different from placebo values. Plasma cortisol and aldosterone increased after stopping Ileu-ANP. Neither urine volume nor sodium excretion rate was significantly increased by Ileu-ANP. PMID- 2878132 TI - Removal and replacement of Tenckhoff catheter at a single operation: successful treatment of resistant peritonitis in continuous ambulatory peritoneal dialysis. AB - 8 episodes of persistent and 4 of recurrent bacterial peritonitis in 11 patients on continuous ambulatory peritoneal dialysis (CAPD) were treated successfully by the removal and immediate replacement of the Tenckhoff catheter. Intraperitoneal antibiotics, which had previously failed to produce clinical resolution of the peritonitis, were continued unchanged. Dialysate culture yielded Staphylococcus epidermidis (3 cases), Staphylococcus aureus (1 case), pseudomonas species (5 cases), acinetobacter (1 case), and no growth in 2 cases. Clinical and microbiological resolution was achieved in all 12 cases within 36 h. CAPD continued uninterrupted in 10 cases. 1 patient required temporary haemodialysis for 6 weeks because of dialysate leakage and later restarted CAPD. 1 patient chose haemodialysis as his long-term treatment when his new catheter failed mechanically on the second postoperative day. Replacement of the Tenckhoff catheter at a single operation without interrupting CAPD reduces the demand which temporary haemodialysis of these patients makes on centre dialysis facilities and may preserve the peritoneal cavity for dialysis by preventing the formation of adhesions. PMID- 2878133 TI - Thunderclap headache: symptom of unruptured cerebral aneurysm. AB - Many patients with a ruptured berry aneurysm report an intense sentinel headache of sudden onset in the weeks before rupture. Such headaches have been attributed to a leak of blood, which implies that partial rupture has occurred. A case is reported of a patient who had severe headaches which seemed to be caused by an unruptured cerebral aneurysm, accompanied by diffuse cerebral vasospasm. Headache episodes with the thunderclap profile may require angiography for diagnosis even if the cerebrospinal fluid is bloodless. PMID- 2878136 TI - Assessment of airflow obstruction. PMID- 2878135 TI - NANC nerves in airways. PMID- 2878134 TI - Role of spinal noradrenergic system in transmission of pain in patients with spinal cord injury. AB - 15 patients with deafferentation pain due to spinal cord injury were investigated for a spinal mechanism of pain transmission. Epidural morphine 5 mg in 5 ml of water had an analgesic effect in 5 patients, 3 of whom also had pain relief with epidural clonidine. Epidural clonidine 150 micrograms in 5 ml of saline had an analgesic effect in 7 patients who did not respond to epidural morphine. Neither epidural morphine nor clonidine was effective in the other 3 patients, 2 of whom obtained relief with epidural buprenorphine 0.3 mg in 5 ml of saline. 1 patient did not find relief with any of the injections. These data suggest that a spinal noradrenergic system may be as important as the opioid system in the transmission of pain in patients with spinal cord injury. PMID- 2878137 TI - Infant botulism. PMID- 2878138 TI - Inflammatory abdominal aortic aneurysms. PMID- 2878139 TI - Say ninety-nine. PMID- 2878140 TI - Bowel flora and ankylosing spondylitis. PMID- 2878142 TI - Gallstone disease--present and future. PMID- 2878141 TI - Primary health care in developing countries: overcoming operational, technical, and social barriers. PMID- 2878143 TI - Blue sclerae: a common sign of iron deficiency? AB - 169 hospital inpatients were studied to assess the association of blue sclerae with iron-deficiency anaemia. Three observers independently graded the signs of blue sclerae and mucosal pallor as absent, equivocal, definite, or striking. Blue sclerae were seen more often in patients with iron-deficiency anaemia (40/46, 87%) than in those with other anaemias (2/28, 7%; p less than 0.001) or without anaemia (5/95, 5.3%; p less than 0.001). The specificity of blue sclerae in iron deficiency anaemia was 0.94 with a sensitivity of 0.87. By comparison, mucosal pallor was noted in only 30% of patients with iron-deficiency anaemia, with a specificity of 0.96 and a sensitivity of only 0.20 (p less than 0.001). The presence of blue sclerae was unaffected by age, sex, or colour of iris. Blue sclerae appear to be a good indicator of iron deficiency and should become a regular part of clinical examination. PMID- 2878144 TI - Is homeopathy a placebo response? PMID- 2878145 TI - Oral contraceptives and breast cancer. PMID- 2878146 TI - Foscarnet in fulminant hepatitis B. PMID- 2878147 TI - Heterogeneity of Escherichia coli J5 vaccines. PMID- 2878148 TI - Comparison of six methods of emergency ventilation. PMID- 2878149 TI - Non-penetrance in tuberous sclerosis. PMID- 2878150 TI - Ataxic neuropathy due to ganglioneuronitis after probable acute human immunodeficiency virus infection. PMID- 2878151 TI - Isolation of human immunodeficiency virus from cerebrospinal fluid of antibody positive virus carrier without neurological symptoms. PMID- 2878153 TI - Persistent neonatal chlamydial infection in a 6-year-old girl. PMID- 2878152 TI - Haemoglobin S and in vitro chloroquine susceptibility of Plasmodium falciparum. PMID- 2878154 TI - Copper chelation and the neuro-ophthalmic toxicity of desferrioxamine. PMID- 2878155 TI - Toxicity of leukaemia therapy in children with Down syndrome. PMID- 2878156 TI - Driving after stroke. PMID- 2878157 TI - Informed consent. PMID- 2878158 TI - Policing the drug industry. PMID- 2878159 TI - Acute renal insufficiency after administration of low-osmolar contrast media. PMID- 2878160 TI - Dilutional hyponatraemia masquerading as subarachnoid haemorrhage. PMID- 2878161 TI - Hands and feet warming in hypothermia. PMID- 2878162 TI - Schwann cell expression of HLA-DR antigen in peripheral neuropathies. PMID- 2878163 TI - Class II MHC antigen expression in adrenal cortex. PMID- 2878164 TI - Nodal metastases from papillary thyroid carcinoma. PMID- 2878165 TI - Valproate toxicity and ornithine carbamoyltransferase deficiency. PMID- 2878166 TI - Hyperphenylalaninaemia in parenterally fed newborn babies. PMID- 2878167 TI - Diabetic ketoacidosis. PMID- 2878168 TI - Diabetes with kidney failure. PMID- 2878169 TI - Trimethoprim resistance. PMID- 2878170 TI - Genetic marker in apolipoprotein AI/CIII gene complex associated with hypercholesterolaemia. PMID- 2878171 TI - Pregnancy rates after high intrauterine insemination of husband's spermatozoa or gamete intrafallopian transfer. PMID- 2878172 TI - Obstetric hysterectomy. PMID- 2878173 TI - Safety and efficacy of warfarin started early after submassive venous thrombosis or pulmonary embolism. AB - Two anticoagulant regimens, similar except for the timing of warfarin therapy, were compared in patients with clinically submassive venous thromboembolism (VTE). Warfarin was begun after 7 days of continuous intravenous heparin infusion in group L (127 patients) or within 3 days (average 1 day) of starting heparin in group S (139 patients), with similar outcomes. The frequency of symptomatic VTE recurrence during the hospital stay was 4.7% in group L and 3.6% in group S, and that of symptomless new perfusion defects 8.5% in group L and 3.9% in group S. On routine iodine-125-fibrinogen leg scanning of patients presenting with distal thrombosis (in the calf, popliteal, or distal femoral veins) 3.6% of group S but no group L patients had symptomless proximal extension. The incidence of bleeding was similar with both regimens. Outpatient follow-up showed no excess recurrent VTE in either treatment group. Early warfarin treatment significantly shortened hospital stay by an average of 3.9 days (30%) in patients admitted solely because of VTE. PMID- 2878174 TI - Multicentre trial of ethamsylate for prevention of periventricular haemorrhage in very low birthweight infants. AB - The effectiveness of ethamsylate in the prevention of periventricular haemorrhage (PVH) in very low birthweight infants was evaluated by means of a multicentre, placebo-controlled, double-blind trial. In 330 infants without evidence of PVH on initial cranial ultrasound examination there was little difference between ethamsylate and placebo groups with respect to subependymal haemorrhage, but intraventricular and parenchymal haemorrhages developed in 30/162 infants (18.5%) in the treated group, compared with 50/168 (29.8%) in the control group (p less than 0.02). The incidence of intraventricular and parenchymal haemorrhage in survivors was 20/137 (14.6%) in the ethamsylate group and 37/146 (25.3%) in the controls (p less than 0.05). In 30 infants with evidence of PVH on the initial scan, ethamsylate treatment seemed to limit parenchymal extension. Analysis of the total cohort of 360 infants showed that the proportion of infants in whom an increase of two or more grades of severity of PVH was recorded during the trial was lower in the treated than in the placebo group (p less than 0.01). No adverse effects were attributed to ethamsylate therapy. The reported incidence of patent ductus arterious was lower in the treated than in the placebo group (p less than 0.02). Mortality was similar in the two groups. PMID- 2878175 TI - Effect of two years of strict metabolic control on progression of incipient nephropathy in insulin-dependent diabetes. AB - 36 patients with insulin-dependent diabetes mellitus who had 'Albustix'-negative urine but raised urinary albumin excretion (30 to 300 mg/24 h) were randomly assigned to either remaining on conventional insulin treatment or continuous subcutaneous insulin infusion and followed up for 2 years. The insulin-infusion group showed a significant, sustained improvement in metabolic control, with a median glycosylated haemoglobin of 7.2% (range 5.9-8.8), but there was no change in the conventional-treatment group (median 8.6%, range 7.2-13.4) (p less than 0.001). Clinical diabetic nephropathy (a urinary albumin excretion rate above 300 mg/24 h in at least two of three 24 h urine collections) developed in 5 patients in the conventional-treatment group, but not in the insulin-infusion group (p less than 0.05, two-tailed). Fractional albumin clearance (mean and range X 10(7] increased in the conventional-treatment group from 160 (35-468) to 360 (29-1580) and was unchanged in the insulin-infusion group (170 [31-608] before to 160 [26 460] after) (p less than 0.05). Insulin infusion had an overall beneficial effect on the annual increase in urinary albumin excretion (p less than 0.05), and the mean glycosylated haemoglobin values correlated positively with annual change in albumin excretion (r = 0.57, p less than 0.0001). The diastolic blood pressure rose significantly in the conventional-treatment group (p less than 0.001), and annual change in mean blood pressure correlated with change in urinary albumin excretion (r = 0.49, p less than 0.001). PMID- 2878176 TI - Self-contained enzymic membrane immunoassay for detection of rotavirus antigen in clinical samples. AB - A self-contained enzymic membrane immunoassay (SCEMIA) system has been developed for the detection of viral antigens in clinical samples. The assay system makes use of antiviral antibodies bound to a nylon membrane, a flow-through washing procedure, and a clearly visible endpoint of the enzymic reaction. A SCEMIA system with antibodies against rotavirus detected rotavirus antigen, within 15 min, in all faecal samples from children with gastroenteritis that were positive for antigen in a standard microplate enzyme immunoassay, which took 4 h to complete. In addition, the SCEMIA could detect rotavirus in faecal samples collected from infected individuals both before and after antigen could be detected by a standard immunoassay system. Rotavirus antigen was not detectable in control children who did not have evidence of rotavirus infection. SCEMIA systems are an accurate, rapid, and inexpensive means for the practical diagnosis of viral infections in human beings. PMID- 2878177 TI - Treatment of malignant endocrine pancreatic tumours with human leucocyte interferon. AB - 22 patients with advanced malignant endocrine pancreatic tumours were treated with human leucocyte interferon 3-6 X 10(6) IU per day. Objective responses (more than 50% reduction in tumour markers or tumour size) were seen in 7/7 with watery diarrhoea/hypokalaemia/achlorhydria syndrome, 3/4 with the Zollinger-Ellison syndrome, 6/9 with "non-functioning" tumours, and 1 with a mixed tumour mainly producing somatostatin. The median duration of response was 8.5 months, and all responders improved clinically. Adverse effects seemed more tolerable than those of cytotoxic treatment. PMID- 2878178 TI - Kaposi's sarcoma: a reversible hyperplasia. AB - Kaposi's sarcoma has many unusual features: for example, the pronounced male preponderance; its appearance in "crops" rather than as primary tumour with metastases; a substantial rate of spontaneous remission; the predictability of involved sites; the lack of aneuploidy; and the strong association with immunodeficiency. These features and other evidence suggest that it is not a malignant neoplasm but a benign, potentially controllable and reversible hyperplasia. PMID- 2878179 TI - Plasma exchange for neurological disorders. PMID- 2878180 TI - Yellow fever in Africa. PMID- 2878181 TI - Urinary incontinence in elderly patients. PMID- 2878182 TI - A long-term view of child psychiatric disorders. PMID- 2878183 TI - Cerebral dominance and epilepsy surgery. PMID- 2878184 TI - Minimum size of the acquired immunodeficiency syndrome (AIDS) epidemic in the United States. AB - A new method based on the reported incubation period of transfusion-associated AIDS was used to estimate the number of AIDS cases likely to arise in the USA among those infected before 1986. Between 1986 and 1991 102,000 new cases are projected, with a total cumulative incidence of 135,000 AIDS cases. These estimates do not account for new infections after 1985 nor very long incubation periods and are thus the smallest numbers to be expected. Even if new infections can be effectively prevented, the epidemic will be five times larger than the number of cases observed so far. PMID- 2878185 TI - Should psychiatric patients be granted access to their hospital records? PMID- 2878186 TI - Body history. PMID- 2878188 TI - Erythropoietin treatment in anaemic patients on haemodialysis. PMID- 2878187 TI - 150th anniversary of the RMBF (Royal Medical Benevolent Fund). PMID- 2878189 TI - Isolation of swine-influenza-like A(H1N1) viruses from man in Europe, 1986. PMID- 2878191 TI - Captopril versus frusemide in moderate heart failure. PMID- 2878190 TI - Findings in four HTLV-IV seropositive women from West Africa. PMID- 2878192 TI - Serum cholesterol, blood pressure, and mortality. PMID- 2878193 TI - Colonoscopy and barium enemas. PMID- 2878194 TI - Cerebral artery Doppler ultrasonography for prediction of outcome after perinatal asphyxia. PMID- 2878195 TI - Sudden infant death syndrome and inherited disorders of fat metabolism. PMID- 2878196 TI - Plasma aluminium and prolonged parenteral nutrition in infancy. PMID- 2878197 TI - Human papillomavirus in squamous carcinoma of anus. PMID- 2878198 TI - Adjuvant chemotherapy in early breast cancer. PMID- 2878199 TI - Neural tube defects, sex ratios, and X inactivation. PMID- 2878200 TI - Biological basis for high-voltage-shock treatment for snakebite. PMID- 2878201 TI - Co-dergocrine. PMID- 2878202 TI - Retinoblastoma, melanoma, and pancreatic cancer. PMID- 2878203 TI - Genetic haemochromatosis and thrombocytopenia. PMID- 2878204 TI - Confidentiality of pre-employment health screening. PMID- 2878205 TI - Legal interference and clinical freedom. PMID- 2878207 TI - Awareness during anaesthesia. PMID- 2878206 TI - Contribution of fetal alcohol syndrome to mental retardation. PMID- 2878208 TI - Brain death. PMID- 2878209 TI - Diastolic versus systolic. PMID- 2878210 TI - Can seroconversion rates to hepatitis vaccine among healthy subjects be improved? PMID- 2878211 TI - Efficacy of Pasteur hepatitis B vaccine in medical students. PMID- 2878212 TI - Intradermal vaccination against hepatitis B. PMID- 2878213 TI - Salivary drug measurement: a cautionary tale. PMID- 2878214 TI - Haptenisation of serum proteins by acetaldehyde. PMID- 2878215 TI - Renal scarring and non-attaching Escherichia coli. PMID- 2878216 TI - Haloperidol-induced dystonia in cocaine addicts. PMID- 2878217 TI - Tumour information from needle biopsy. PMID- 2878218 TI - Campylobacter pyloridis infection as possible complication of weight loss therapy. PMID- 2878219 TI - Leukaemic relapse following Campath 1 treated bone marrow transplantation for leukaemia. PMID- 2878220 TI - Prevention of migrainous headaches by tamoxifen. PMID- 2878221 TI - Rheumatoid arthritis and tuberculosis in Africa. PMID- 2878222 TI - A doctor's inexperience is no defence to a claim for negligence. PMID- 2878224 TI - Coronary artery bypass graft failure--an autoimmune phenomenon? AB - Plasma anticardiolipin antibody (ACA) was measured in 83 patients having coronary artery bypass graft surgery and results were correlated with the incidence of early (1-2 weeks) and late (12 months) graft occlusion, as judged by angiography. There was an association between preoperative ACA level and the incidence of late graft occlusion in relation to both number of patients with an occlusion and number of distal anastomoses occluded. 8 of 15 patients (53.3%) whose maximum ACA level exceeded 4 SD of the mean of controls had a late graft occlusion. When the ACA titre was 2-4, 0-2, or less than 0 SD above the mean of the controls, the occlusion rates were 3 of 13 (23.1%), 3 of 33 (9.1%), and 1 of 15 (6.7%), respectively (p less than 0.03). The incidence of a postoperative rise in ACA level was higher in patients who had had a myocardial infarction in the past than in those with a history of angina only (chi 2 = 4.08, p less than 0.05). This observation supports the notion that one mechanism of ACA production is an immune response to myocardial injury. These results raise the further possibility that the ACA, or related antiphospholipid antibodies, may play a part in progressive coronary vessel disease. PMID- 2878223 TI - Islet-cell antibodies and insulin autoantibodies in association with common viral infections. AB - The appearance of islet-cell antibodies (ICA) and insulin autoantibodies (IAA) was sought in a prospective study of subjects with acute infections (mumps, rubella, chickenpox, and measles) followed for 6 months. IAA appeared in many patients' serum samples after these acute infections, IgM-IAA being more prevalent than IgG-IAA; there was a particularly high incidence (81%) after chickenpox. ICA were detected in 2 subjects--in 1 after rubella and in the other after measles, but this patient had evidence of previous rubella and a strong autoimmune family history. ICA did not appear after mumps. It is postulated that viral infections may trigger the production of IgM-IAA by a common mechanism involving polyclonal immunocyte activation. PMID- 2878225 TI - Suicide attempts in hypo-oestrogenic phases of the menstrual cycle. AB - The phase of the menstrual cycle in women who had attempted suicide was determined by structured interview. 108 young women were investigated within 24 h of the attempt. Patients were grouped according to menstrual week and whether they used oral contraception (OC) (n = 73) or not (n = 35). In OC non-users suicide attempts were associated with low plasma oestradiol: they tended to happen during the first week of the menstrual cycle (42%) and after the fourth week (12%). Frequency of suicide attempts did not vary significantly during the menstrual cycle in OC users. In OC non-users, low oestradiol production may predispose to depression and attempted suicide. PMID- 2878226 TI - Cardiac pumping capability and prognosis in heart failure. AB - In 63 patients with severe acute or chronic heart failure maximum cardiac performance was determined by calculation of the maximum hydraulic power output achieved by the heart during dobutamine challenge. After one year, all but 3 of the 23 patients with maximum cardiac power output (Wmax) less than the normal resting value of 1 W had died of progressive heart failure. Of the 40 with Wmax more than 1 W, all but 4 (who died suddenly) survived longer than one year. Hydraulic power output is a clinically important measure of cardiac pumping performance and a maximum power output value below the normal resting value indicates that long-term survival is unlikely. PMID- 2878228 TI - Prevalence of lumbar disc degeneration observed by magnetic resonance in symptomless women. AB - 302 women aged 16-80 without symptoms of spinal disease had their lumbar intervertebral discs examined by magnetic resonance. The prevalence of one or more degenerate discs increased linearly with age but disc degeneration was already present in over one-third of women aged 21-40; these young women may prove to be at special risk of disc prolapse later in life. The high prevalence of symptomless disc degeneration must be taken into account when magnetic resonance is used for assessment of spinal symptoms. PMID- 2878227 TI - Raised serum levels of tumour necrosis factor in parasitic infections. AB - In a study of serum levels of endogenous tumour necrosis factor (TNF) in healthy people and patients with neoplastic or infectious disease, only patients with kala-azar (visceral leishmaniasis) and malaria were found to have a strikingly increased frequency of raised TNF levels (66.6% and 70.0%, respectively). 7.9% of samples from both healthy subjects and patients with neoplastic disease contained measurable TNF. The discovery of elevated TNF levels in the sera of patients with parasitic diseases suggests that this cytokine may play a part in host defences against parasitic infections. PMID- 2878230 TI - Reciprocal changes accompanying acute myocardial infarction. PMID- 2878229 TI - Prenatal screening for irregular blood group antibodies. PMID- 2878231 TI - Pituitary tumours and the empty sella syndrome. PMID- 2878232 TI - Pulmonary infection in cystic fibrosis--still a sticky problem. PMID- 2878233 TI - Serodiagnosis of Candida infections. PMID- 2878234 TI - Climatic droplet keratopathy. PMID- 2878235 TI - Research on human embryos. PMID- 2878236 TI - Giving up smoking and the risk of heart attacks. A report from The British Regional Heart Study. AB - In a prospective study of 7735 middle-aged men, both current and ex-cigarette smokers had a risk of a major IHD event, within an average 6.2 years of screening, more than twice that in men who had never smoked cigarettes; men who had given up smoking more than 20 years ago still had an increased risk. This excess risk among ex-smokers is only to a small extent explained by their higher blood pressure, serum total cholesterol, and body-mass index. An increased prevalence of IHD in men who had recently given up smoking also made a small contribution to excess risk. In both current and former cigarette smokers, the number of years a man had smoked cigarettes ("smoking-years") was the clearest indicator of IHD risk due to cigarettes. The major benefit of giving up smoking may lie in halting the accumulation of smoking years. PMID- 2878237 TI - Medical admissions in men: the risk among drinkers. AB - Information on alcohol consumption was elicited by the same method from men in a general population survey and from male medical inpatients in a hospital serving that population. A measure of risk controlling for age, the logarithm of the odds ratio, showed that for liver disorders, upper gastrointestinal disorders, myocardial infarction, other cardiovascular disorders, and respiratory disorders, rising consumption of alcohol was related to increased risk of hospital admission relative to abstention. The risk of admission for the remaining heterogeneous category of disorders was lower than that for abstention, perhaps reflecting the effect of chronic illness on drinking habits, and also suggesting that the link between alcohol consumption and medical diagnoses is not simply due to greater frankness about drinking in hospital inpatients. PMID- 2878238 TI - Organ procurement for children: the anencephalic fetus as donor. PMID- 2878239 TI - A sexist diagnosis? PMID- 2878240 TI - Appropriate technology following birth. PMID- 2878241 TI - Sleep disruption, calorie restriction, and biological markers for depression. PMID- 2878242 TI - Incubation period of fifth disease. PMID- 2878243 TI - Magnetic resonance spectroscopy in ischaemic feet. PMID- 2878244 TI - HIV-I and HIV-II double infection in Central African Republic. PMID- 2878245 TI - Lack of HIV infection and condom use in licensed prostitutes. PMID- 2878246 TI - Azidothymidine neurotoxicity. PMID- 2878247 TI - Paraplegia after intrathecal mitozantrone. PMID- 2878248 TI - Hypercholesterolaemia after administration of nicotine chewing gum. PMID- 2878249 TI - Bedside theophylline assay in severe acute asthma. PMID- 2878250 TI - Acceptability of prenatal diagnosis for retinitis pigmentosa. PMID- 2878251 TI - Attitudes to early diagnosis of polycystic kidney disease. PMID- 2878252 TI - Enalapril-induced nasal blockage. PMID- 2878254 TI - Mild atypia on cervical smear warrants further investigation. PMID- 2878253 TI - Changes in brain water in systemic lupus erythematosus. PMID- 2878255 TI - Paroxysmal nocturnal haemoglobinuria and pregnancy. PMID- 2878256 TI - Is it necessary to deny patients with renal failure fruit-flavoured beverages? PMID- 2878257 TI - Serum aluminium levels in acute renal failure. PMID- 2878258 TI - Cyclosporin metabolites and nephrotoxicity. PMID- 2878259 TI - Serological evidence against role for canine distemper virus in pathogenesis of Paget's disease of bone. PMID- 2878260 TI - Osteopenia in very low birthweight infants. PMID- 2878261 TI - Absence of antibodies to Yersinia enterocolitica in patients with ankylosing spondylitis in London. PMID- 2878262 TI - Germs and joints. PMID- 2878263 TI - Peripheral symmetrical gangrene successfully treated with epoprostenol and tissue plasminogen activator. PMID- 2878264 TI - Successful induction with chemotherapy including teniposide in familial erythrophagocytic lymphohistiocytosis. PMID- 2878265 TI - Monoclonal antibodies for rapid identification of Campylobacter pyloridis. PMID- 2878266 TI - Long term pathology of lung, eye, and other organs following acute exposure of rats to methyl isocyanate. PMID- 2878267 TI - Is steroid psychosis preventable by divided doses? PMID- 2878268 TI - Leukaemic relapse after Campath 1 treated bone marrow transplantation for leukaemia. PMID- 2878270 TI - Amoeba research and history. PMID- 2878269 TI - Hyperphenylalaninaemia in parenterally fed newborn babies. PMID- 2878271 TI - Non-endoscopic relief of oesophageal obstruction. PMID- 2878272 TI - Multicentre double-blind study of effect of intrathecally administered natural human fibroblast interferon on exacerbations of multiple sclerosis. AB - In this randomised, double-blind, placebo-controlled, 2-year multicentre study intrathecally administered natural human fibroblast interferon (IFN-B) was effective in reducing exacerbations of multiple sclerosis (MS) in patients with exacerbating/remitting disease. The mean reduction in exacerbation rate of 34 patients who received IFN-B (recipients) was significantly greater during the study than that of 35 patients who received placebo (p less than 0.04). The prestudy exacerbation rates were comparable in recipients and controls, but the rate at the end of the study was significantly lower in recipients than in controls (p less than 0.001). IFN-B was given by nine or ten lumbar punctures over the first 6 months of the study, and patient observations continued for 2 years. IFN-B was well tolerated in 95% of the recipients, and the side-effects experienced were clearly acceptable for the benefits achieved. Low doses of indomethacin reduced the toxicity of IFN-B and played an important role in successful double-blinding. PMID- 2878273 TI - Fine-catheter aspiration cytology of peritoneal cavity improves decision-making about difficult cases of acute abdominal pain. AB - Fine-catheter aspiration cytology of the peritoneal cavity was successfully undertaken in 25 of 27 hospital inpatients with acute abdominal pain because it was not clear whether they required urgent laparotomy. Cytological specimens were prepared by the cyto-sieve technique. The main test criterion was the percentage of neutrophils in the peritoneal cell sample. The decision before the test about urgent laparotomy was correct in 14 of the 27 patients, whereas the decision after the test was correct in 26 of the 27 patients (p = 0.001). 4 patients were saved unnecessary laparotomy and 8 further delay in laparotomy. PMID- 2878274 TI - Controlled trial of acupuncture for disabling breathlessness. AB - In a randomised controlled trial, twelve matched pairs of patients with chronic obstructive pulmonary disease received traditional Chinese acupuncture or placebo acupuncture. After three weeks' treatment the traditional-acupuncture group showed significantly greater benefit in terms of subjective scores of breathlessness and six-minute walking distance. Objective measures of lung function were unchanged in either group. Whether these differences are mediated by endogenous opiate and/or peptide release remains speculative. PMID- 2878275 TI - Attenuation of exercise-induced asthma by acupuncture. AB - A prospective randomised single-blind study of the effects of real and sham acupuncture on exercise-induced asthma was conducted in nineteen children. Forced expiratory flow in 1st second (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEFR) were measured throughout acupuncture and after treadmill exercise. Neither real nor sham acupuncture affected the basal bronchomotor tone but both, when applied 20 min before exercise, attenuated exercise induced asthma: mean maximum percentage falls in FEV1, FVC, and PEFR were 44.4%, 33.3%, and 49.5% without acupuncture; 23.8%, 15.8%, and 25.9% after real acupuncture; and 32.6%, 26.1%, and 34.3% after sham acupuncture. Real acupuncture provided better protection against exercise-induced asthma than did sham acupuncture (p less than 0.05). PMID- 2878276 TI - A non-invasive method for measuring cardiac output: the effect of Christmas lunch. AB - Cardiac output was measured in ten patients at routine cardiac catheterisation and three patients with severe heart failure by means of a carbon dioxide rebreathing technique with a computer-assisted mass spectrometer and compared with cardiac output measured by thermodilution. There was a close correlation (r = 0.96, p less than 0.01) between the two methods. Cardiac output measured by the carbon dioxide rebreathing technique increased after a typical Christmas lunch by a mean of 1.6 1/min in a group of healthy volunteers. PMID- 2878277 TI - Paradoxical deterioration in lung function after nebulised salbutamol in wheezy infants. AB - In 13 infants with a history of wheezing, airways resistance and specific conductance worsened after administration of nebulised salbutamol (0.5 ml sabutamol respirator solution in 1.5 ml normal saline). This paradoxical bronchoconstriction was greatest at 5 min and lasted for up to 15 min. The nebulised solution was found to be acidic and hypo-osmolar, both of which properties have been linked to bronchoconstriction in asthmatic subjects, but even with an initially iso-osmolar solution osmolality increased with time of nebulisation because of evaporation. PMID- 2878278 TI - Acupuncture, asthma, and breathlessness. PMID- 2878279 TI - Screening for hearing impairment in the newborn. PMID- 2878280 TI - An unexpected new human virus. PMID- 2878281 TI - Physical activity in old age. PMID- 2878283 TI - Anti-oestrogenic effect of cigarette smoking. PMID- 2878282 TI - Penicillin prophylaxis for babies with sickle-cell disease. PMID- 2878284 TI - Not an annual bleat: the MRC annual report for 1985/86. PMID- 2878286 TI - Common-sense beliefs about illness: a mediating role for the doctor. AB - A great deal is said these days about how important it is for doctors to pay attention to the patient's beliefs about his or her disease. Better knowledge of such beliefs, it is argued, will enable the doctor to counter ignorance, enhance communication, and reduce non-compliance. The view advanced here is that the significance of patients' beliefs and their frequent resistance to rational correction will emerge only if they are seen as components in a process of "narrative reconstruction". It is suggested that the main difficulty is not ignorance but rather the fact that doctor and patient have different purposes: whereas the doctor's objective is to explain the aetiology of the disease, the patient may be more concerned to make sense of the disruption caused by the disease. PMID- 2878285 TI - Diagnosis: the need for demystification. PMID- 2878287 TI - Art in hospitals and for the disadvantaged in New York and London. PMID- 2878289 TI - Finding able minds in disabled bodies. PMID- 2878288 TI - Who's afraid of angina pectoris? Separating the symptom from the marker. AB - 100 cardiologists were asked for their views on the risk associated with an episode of exertional angina in patients with stable angina. 58% thought that such an episode carried some risk of permanent damage or death, and 78% advised their patients to avoid anginal pain. In contrast, exercise studies done during the evaluation of anti-anginal drugs indicate that exertional angina can be provoked frequently and repeatedly without apparent risk, and other studies have shown that repeated exercise to the onset of angina is not only safe but improves exercise tolerance. Epidemiological investigations suggest that sudden death and myocardial infarction do not commonly occur during exertion, and our knowledge of pathology indicates that both events are usually caused by acute coronary thrombosis. Many physicians seem to treat the symptom of angina because they are unduly motivated by fear of the underlying potentially fatal disease for which angina is a marker. Such an attitude will tend to cause undue anxiety among patients, will lead to unnecessary restriction of patients' activities, and may result in excessive invasive treatment of mild angina. PMID- 2878291 TI - Montaigne's insight: placebo effect and symptom anticipation are two sides of the same coin. PMID- 2878290 TI - The European exchange scheme for junior doctors in internal medicine. An exciting and successful experiment. PMID- 2878292 TI - Kouska's fallacy: the error of the divided denominator. AB - The significance of two normally independent findings in a single patient is often difficult to assess. One simple measure of the likelihood of random coincidence is the joint probability, based on the assumption that the findings are independent. Unfortunately, this technique is often used wrongly. The error is the division of an event into its components, followed by calculation of their joint probability. These two processes, used together, make the likelihood of a common event happening seem very improbable. This can be termed the error of the divided denominator, or Kouska's fallacy, after a fictional character who used this technique to disprove the existence of life. PMID- 2878293 TI - Attempted bone-marrow transplantation in a 17-week fetus. PMID- 2878294 TI - Complete response of congenital fibrosarcoma to chemotherapy. PMID- 2878295 TI - Community outbreak of multiresistant invasive Escherichia coli infection. PMID- 2878296 TI - Outbreak of non-menstrual fatal staphylococcal toxic shock syndrome in India. PMID- 2878297 TI - Soft-tissue sarcomas, malignant lymphomas, and 2,3,7,8-TCDD exposure in Seveso. PMID- 2878298 TI - Recurrent parotitis with H2 receptor antagonists. PMID- 2878299 TI - Anti-IgM screening for HIV. PMID- 2878301 TI - Pre-S2 antibodies in hepatitis B. PMID- 2878302 TI - Hepatitis B vaccine for police forces? PMID- 2878303 TI - Inflammatory abdominal aortic aneurysms. PMID- 2878300 TI - Fluid retention with nifedipine in antihypertensive therapy. PMID- 2878305 TI - Neonatal varicella infection. PMID- 2878306 TI - Future of Health Education Council. PMID- 2878307 TI - Population growth and resource allocation. PMID- 2878304 TI - Thunderclap headache and unruptured cerebral aneurysm. PMID- 2878308 TI - Legalising heroin. PMID- 2878309 TI - Conduct of research on amrinone. PMID- 2878310 TI - Death of a child in Africa. PMID- 2878311 TI - Post-partum haemorrhage is associated with poor housing, not multiparity, in Botswana. PMID- 2878312 TI - Comparison of human and rabbit brain thromboplastin in evaluation of haemostatic defect of liver disease. PMID- 2878313 TI - Prosthesis for malignant oesophago-respiratory fistula. PMID- 2878314 TI - Cerebral dominance and epilepsy surgery. PMID- 2878315 TI - A cure for Santa's sleep apnoea. PMID- 2878316 TI - Serotoninergic treatment of screaming and banging in dementia. PMID- 2878317 TI - Postvagotomy diarrhoea. PMID- 2878318 TI - Risk/benefit of heparin-dihydroergotamine thromboembolic prophylaxis. PMID- 2878319 TI - Heparin and mast cells. PMID- 2878320 TI - Human papillomavirus type 16 DNA at biopsy of gingival hyperplasia after cardiac transplantation. PMID- 2878321 TI - End-stage renal failure in diabetes. PMID- 2878322 TI - Examining the parents of children with tuberous sclerosis. PMID- 2878324 TI - Simple system for central rewarming of hypothermic patients. PMID- 2878323 TI - Renewal of Tenckhoff catheters. PMID- 2878325 TI - Direct intraperitoneal insemination: first results confirmed. PMID- 2878326 TI - Borderline antibody response in initial stages of lymphocytic meningitis does not rule out borreliosis. PMID- 2878327 TI - Iron, akathisia, and antipsychotic drugs. PMID- 2878328 TI - Syphilis in the elderly. PMID- 2878329 TI - Unilateral fixed dilated pupil associated with nebulised ipratropium bromide. PMID- 2878330 TI - Italian smallpox of the sixteenth century. PMID- 2878331 TI - Activated clotting factors in haemophilia (1840) PMID- 2878332 TI - Screening siblings for inborn errors of fatty acid metabolism in families with a history of sudden infant death. PMID- 2878333 TI - [Somatostatin immunoreactive cells of Vater's ampulla and the peripapillary duodenum]. PMID- 2878334 TI - Regulation of chicken pineal arylalkylamine-N-acetyl transferase by postsynaptic alpha 2-adrenergic receptors. AB - The present investigation sought to characterize the adrenergic inhibition of arylalkylamine-N-acetyltransferase in cultured chicken pineal glands. Arylalkylamine-N-acetyltransferase, the melatonin rhythm generating enzyme, displays daily oscillations of activity that are driven by a circadian oscillator. Norepinephrine released at sympathetic nerve endings inhibits the enzyme and appears to play a role in maintaining a circadian rhythm of melatonin release. Chicken pineal glands were isolated in organ culture and the effects of adrenergic agents on the night time peak of N-acetyltransferase activity were studied. Norepinephrine and clonidine prevented 50 to 65% of the nocturnal rise of N-acetyltransferase activity. When applied at middark, norepinephrine and clonidine caused a 50 to 65% inhibition of N-acetyltransferase activity in 2 hours. Dose-response studies indicated clonidine was 100 times more potent than norepinephrine or cirazoline at inhibiting N-acetyltransferase activity. Inhibition of N-acetyltransferase activity was also observed, at micromolar concentration with epinephrine, UK 14,304 and alpha-methylnorepinephrine but not with phenylephrine, isoproterenol or dopamine. Epinephrine and clonidine actions were antagonized by yohimbine but not by prazosin. Destruction of the presynaptic compartment by bilateral superior cervical ganglionectomy did not affect the clonidine-induced inhibition of N-acetyltransferase and its reversal by yohimbine. It is concluded that the adrenergic inhibition of N-acetyltransferase activity in chicken pineal gland probably occurs via stimulation of postsynaptic alpha 2-adrenergic receptors. PMID- 2878335 TI - Effect of tyrosine administration on dopa accumulation in light- and dark-adapted retinas from normal and diabetic rats. AB - The interaction of tyrosine concentration and lighting on in vivo dihydroxyphenylalanine (dopa) accumulation rate was studied in retinas of normal and diabetic rats. In both groups of rats, dopa accumulation and in vitro hydroxylase activity were higher in retinas exposed to light than in those adapted to darkness. In light-adapted diabetic rats, though, retinal tyrosine level, dopa accumulation, and in vitro tyrosine hydroxylase activity were all below normal. In both normal and diabetic rats exposed to light, tyrosine injection raised retinal tyrosine concentrations and stimulated dopa accumulation. Injection of tyrosine into dark-adapted rats raised retinal tyrosine level but did not enhance dopa accumulation. Together, these results suggest that in vivo retinal amacrine cells will vary their dopa accumulation rate as a function of substrate supply, but only in the light, when tyrosine hydroxylase is activated. They further indicate that dopa accumulation rate remains sensitive to tyrosine supply in the light-activated diabetic retina. PMID- 2878336 TI - Existence of antiopiate systems as illustrated by MIF-1/Tyr-MIF-1. AB - Evidence is presented that the small peptides MIF-1/Tyr-MIF-1 are part of an endogenous antiopiate system that may function to balance the opiate system. We review the biological activity, behavioral activity, and functional effects of this proposed opiate antagonist system. In addition, we suggest, based on antinociceptive mechanisms, that the individual components of the antiopiate system might function differently from naloxone. PMID- 2878337 TI - A rapid and sensitive assay for tyrosine-3-monooxygenase based upon the release of 3H2O and adsorption of [3H]-tyrosine by charcoal. AB - A rapid, simple and sensitive assay has been developed for tyrosine-3 monooxygenase, the enzyme catalyzing the rate-limiting step in catecholamine biosynthesis. The assay is based upon the release of 3H2O from 3H-[3,5]-L tyrosine with adsorption of the isotopic substrate (and its metabolites) by an aqueous slurry of activated charcoal. This method routinely yields low blank values and is simpler than the procedure requiring the use of cation exchange columns to separate the isotopic substrate from the 3H2O formed during the hydroxylation reaction. PMID- 2878338 TI - Cerebral metabolism during cross-circulation in experimental hepatic failure in the pig. AB - The effect of hepatic assistance on cerebral metabolism was evaluated in a series using cross-circulation, anticipating increased efficiency of hepatic support. The experimental model for liver failure was pigs with totally devascularized liver. Cross-circulation with a normal sibling pig, cross-circulation with inflow in the donor directly into the portal vein and cross-perfusion with isolated perfused liver starting 20 h after elimination of liver function in the recipient and lasting for 3 h did not increase survival. Before cross-circulation in these three groups, the cerebral flow and oxygen uptake were decreased; during the cross-circulation a significant but temporary increase was found. In experiments with early and prolonged perfusion with isolated perfused liver no changes in cerebral flow, oxygen or glucose uptake were found, and these variables were still normal 6 h after termination of the perfusion. The survival time was significantly increased. In the control group a significant rise in blood and CSF ammonia was found with a mean CSF/blood ratio of 0.92. After cross-circulation, the CSF/blood ratio was 0.52 and 0.62, respectively, indicating a proportionally greater elimination of ammonia from the cerebrospinal fluid than from the blood. Cross-circulation did not significantly change the alpha-ketoglutarate, glutamate or glutamine CSF concentrations. After prolonged cross-perfusion, the ammonia blood/CSF ratio was 0.24. It is concluded that by extended extracorporeal hepatic assistance it is possible to increase survival and to prevent changes in cerebral metabolism and ammonia accumulating in the cerebrospinal fluid. PMID- 2878340 TI - [Use of two new non-depolarizing muscle relaxants in renal transplantation]. PMID- 2878339 TI - [New muscle relaxants--atracurium and vecuronium]. PMID- 2878341 TI - [Clinical evaluation of vecuronium at the National Taiwan University Hospital]. PMID- 2878342 TI - H2-receptor antagonists and gastric cancer. PMID- 2878343 TI - Adverse reactions and interactions with H2-receptor antagonists. AB - Histamine H2-receptor antagonists have been used in the treatment of gastrointestinal diseases for more than a decade and during this period have become one of the most commonly prescribed groups of drugs in the world. The deserved popularity of the H2-receptor antagonists reflects, in part, their therapeutic efficacy, which has revolutionised the treatment of peptic ulcer disease. An equally, or more, important reason for the widespread use of H2 receptor antagonists is their remarkably low toxicity. We have attempted, in this review, to present a detailed account of the minor and more serious adverse reactions, while emphasising the low incidence of the former and the rarity of the latter. The toxicology of the H2-receptor antagonists is discussed under two main headings: adverse effects; and drug interactions. The latter category is potentially the more significant, since the frequent use of therapy with multiple drugs may give rise to drug interactions, some of which are serious and may even be lethal. These drug interactions occur especially in the gastrointestinal tract, the liver and the kidneys. Thus, the absorption of other drugs may be altered because the H2-receptor antagonists inhibit gastric secretion--an effect illustrated by ketoconazole, the absorption of which is reduced when given in combination with cimetidine. Very important drug interactions are caused by inhibition of the hepatic microsomal enzyme cytochrome P450 by some of the H2 receptor antagonists. This effect appears to be related to the chemical structure of the individual H2-receptor antagonists and is not attributable to histamine H2 receptor blockade. For example, cimetidine is a powerful inhibitor of cytochrome P450, while the interaction of ranitidine with this system is weaker. Consequently, cimetidine reduces the metabolism of many drugs which are normally degraded by phase I reactions, leading to potentially toxic plasma concentrations of therapeutic agents such as some oral anticoagulants, beta-blockers, anticonvulsants, benzodiazepines and xanthines. Some of the H2-receptor antagonists are actively secreted by the renal tubules and may thus compete with other drugs for cationic tubular transport mechanisms, resulting in reduced urinary excretion and hence potentially toxic plasma concentrations. This type of drug interaction has been reported after administration of both cimetidine and ranitidine with procainamide or quinidine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2878345 TI - Adverse effects associated with the newer inotropic agents. AB - The ideal inotropic agent should be available for both parenteral and oral administration and be potent and effective long term without significant adverse effects. In recent years, numerous new agents have been developed in an attempt to find a more potent, less toxic alternative to digoxin. beta-Agonists, while useful when given parenterally short term, appear to have their long term oral application limited by adverse effects and the development of tolerance. A number of other non-catecholamine agents, most of which have both inotropic and vasodilator actions, have also been studied. Adverse effects have been relatively frequent and occasionally severe. Of these newer agents none has yet been proven in clinical trials to be safe and effective in the long term. PMID- 2878344 TI - Adverse reactions to beta 2-agonist bronchodilators. AB - Beta 2-Agonists are safe and effective bronchodilator drugs. Their major adverse effects of skeletal muscle tremor, tachycardia and various metabolic effects are mediated by beta-adrenoceptor stimulation and are reversible. Skeletal muscle tremor is the most frequent dose-limiting side effect. It may be reduced by commencing treatment with a low dose and if it persists another beta 2-agonist may be tried. Other side effects such as cardiac arrhythmias and reduction in PaO2 are a serious potential problem in some susceptible asthmatics. However, they are infrequent or of a mild degree and are generally outweighed by the good control of asthma produced by beta 2-agonists. Side effects from beta 2-agonist therapy can be minimised by use of the inhaled route which selectively delivers the drug to the airways. Furthermore, selective tolerance develops to their side effects. The dose of a beta 2-agonist should be assessed on the basis of therapeutic effect and the level of tolerance to its side effects. Recommended doses of beta 2-agonists used for long term therapy do not cause clinically significant desensitisation of airway beta-adrenoceptors, although this may become a relevant problem in patients who are regularly receiving very high doses. Intravenous beta 2-agonists have a place in the treatment of severe asthma not responding to nebuliser therapy. In this life-threatening situation with severe airflow obstruction, monitoring of heart rate, PaO2, plasma potassium and the electrocardiogram should be mandatory and supplemental oxygen given so that serious adverse effects are presented. PMID- 2878346 TI - Adverse reactions and interactions with beta-adrenoceptor blocking drugs. AB - beta-Blocking drugs are widely used throughout the world and serious adverse reactions are relatively uncommon. Most of those which do occur are pharmacologically predictable and may be avoided by ensuring that patients who are to be given beta-blockers do not have a predisposition to the development of bronchospasm, cardiac failure or peripheral ischaemia. In some situations, the use of a beta 1-selective blocking drug may reduce the risk of a severe adverse reaction, but there is little evidence that other ancillary properties such as partial agonist activity are of relevance in this context. Long term experience with many of the beta-blockers in current use suggests that unpredictable major adverse reactions such as the practolol oculomucocutaneous syndrome are unlikely to be repeated, although some of these drugs may be associated with immunological disturbances and some have been implicated in the development of retroperitoneal fibrosis. beta-Blocking drugs appear to be associated with a number of subjective side effects including muscle fatigue, peripheral coldness and some neurological symptoms. These side effects are highly subjective and are therefore difficult to quantify and it is not known whether they are of major importance in terms of their effect upon patients' overall well-being. It cannot be assumed that simply because such side effects can be elicited that they do, in fact, matter. However, because beta-blockers are often prescribed for patients who have no symptoms and for whom the benefits of therapy are generally small, such side effects would be of considerable importance if they had an overall effect upon quality of life. There are theoretical reasons to suppose that the incidence and severity of such side effects may be related to the ancillary properties of the individual drugs, but there is little evidence that parameters such as beta 1-selectivity, or partial agonist activity are clinically important determinants of the severity of these side effects. Lipophilicity, however, may be associated with an increased incidence of neurological symptoms. beta-Blocking drugs may cause a variety of metabolic disturbances including an increase in serum VLDL-cholesterol concentrations. However, long term studies have not shown that such disturbances are associated with an increased risk of cardiovascular disease, indicating that such metabolic changes may not be of major importance in practice. beta-Blocking drugs may be involved in a number of interactions with other drugs, but few of these have been shown to be of clinical significance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2878347 TI - Abnormal catecholamine metabolism in pheochromocytoma. PMID- 2878348 TI - [Treatment of cancer pain has a special place. Basic principles of pain therapy in tumor patients]. PMID- 2878349 TI - Further evaluation of an immunoprecipitation assay for TSH-receptor autoantibodies in Graves' disease. AB - In ten patients with untreated Graves' disease, quantitative titers of TSH receptor antibodies, as measured by a recently developed immunoprecipitation assay (IPA), were correlated with results obtained in three other methods and with the severity of the hyperthyroidism, as assessed by thyroid function tests. Nine patients were positive in the IPA, six in the TBII (TSH-binding inhibitor immunoglobulins), six in the TSI (thyroid-stimulating immunoglobulins), and seven in the TGI (thyroid-growth stimulating immunoglobulins) assay. Three patients were positive in all four assays. No correlation was found between the IPA values and the results obtained in the TBII, TSI, or TGI assays. There was a modest correlation between the TBII and TSI assays (r = .74, P less than 0.02). There was a modest but significant correlation between the IPA titers of TSH receptor antibodies and serum T3 concentration, both before treatment (r = .63, P less than 0.05) and during treatment (n = 5; r = .84, P less than 0.05). No correlation between the severity of the hyperthyroidism and TBII, TSI, or TGI assays was observed. Finally, TGI did not correlate with goiter size as estimated by palpation. These results suggest that the IPA may be useful in monitoring the immunologic activity of TSH receptor antibodies in patients with Graves' disease. They suggest further that the IPA detects a number of different subpopulations of TSH receptor antibodies, including TSI, TBII, and perhaps TGI. This property may be particularly useful in screening for monoclonal TSH receptor antibodies. PMID- 2878351 TI - Drugs for cardiac arrhythmias. PMID- 2878350 TI - Establishment of an assay system for the detection of translated materials of T cell-replacing factor mRNA in Xenopus oocytes. AB - We established an assay system for detecting T cell-replacing factor (TRF) activity of translated materials in Xenopus oocytes of poly (A)-positive mRNA extracted from a T cell hybrid cell line, B151K12 (B151) which constitutively produces TRF. Since it was difficult to detect TRF activity of the translated products of B151-mRNA, partly because of low TRF activities, we developed the following two systems. First, RNA was prepared from B151 cells stimulated with phorbol myristate acetate and calcium ionophore A23187 because such stimulations augmented TRF production by approximately three to five-fold. Second, interleukin 2 (IL-2, 125 U/ml) was added to the culture of BCL1 cells to detect a small amount of TRF-active materials since IL-2 synergizes with a suboptimal dose of TRF to induce IgM secretion in TRF-responding BCL1 cells (chronic B cell leukemic cells). Here we describe TRF activity of translation products of B151-mRNA in Xenopus oocytes. B151-TRF mRNA was detected in the fractions sedimented between 15 and 18S by analysis using sucrose density gradient centrifugation. PMID- 2878352 TI - Buspirone: a non-benzodiazepine for anxiety. PMID- 2878353 TI - [Neuroleptics and tranquilizers: indications and dangers]. PMID- 2878354 TI - [Immunomodulation caused by histamine and H2 antagonists]. PMID- 2878355 TI - [Takayasu arteritis]. PMID- 2878356 TI - [Familial testicular tumors. Arguments for the effect of genetic factors]. PMID- 2878357 TI - [H2 blockers in a new dosage form: effect on the endocrine system?]. PMID- 2878359 TI - [Neuromas of the orofacial structures and the type 2-b multiple endocrine adenopathy syndrome]. PMID- 2878358 TI - [Intraindividual comparison of 2 bisoprolol dosages in patients with essential hypertension]. PMID- 2878360 TI - Pharmacological approaches to the treatment of eating disorders. PMID- 2878361 TI - Regulation of insulin mRNA abundance and adenylation: dependence on hormones and matrix substrata. AB - The insulin mRNA levels of rat insulinoma cell lines increased six- to eightfold, and the cells entered a transient state of growth arrest when they were cultured in serum-free, hormonally defined medium and on an extract of extracellular matrix derived from a basement membrane-secreting tumor line, EHS. Insulinoma cultures in growth arrest responded to glucose with a two- to threefold increase in insulin secretion associated with an insulin mRNA that contained a poly(A) tail that was 120 to 140 bases longer than normal. PMID- 2878362 TI - Sequences near the 3' secretion-specific polyadenylation site influence levels of secretion-specific and membrane-specific IgG2b mRNA in myeloma cells. AB - The expressed immunoglobulin gamma 2b (IgG2b) heavy-chain gene of 4T001 was cloned into the shuttle vector pSV2-gpt and transfected into myeloma J558L and lymphoma A20.2J. Northern blots indicated that the transfected gamma 2b gene was processed in a manner similar to the endogenous heavy chain in both lymphoma and myeloma cells. To identify sequences important for immunoglobulin mRNA processing, we constructed deletions around the secretion-specific polyadenylation site and introduced the deleted genes into J558L cells. The BAL deletion lacked 670 base pairs of intervening sequence between secreted and membrane regions; the Kpn deletion lacked 830 base pairs in this region. J558L cells transfected with either the entire gamma 2b gene or the delta BAL vector produced predominantly secretion-specific gamma 2b mRNA and protein. J558L cells transfected with the delta Kpn vector produced approximately equimolar amounts of secretion-specific and membrane-specific gamma 2b mRNA. Both 55,000-dalton secreted and 62,000-dalton putative surface IgG2b proteins were detected in the delta Kpn transfectants. We conclude that sequences absent in the Kpn deletion but present in the BAL deletion exert an important role in the production of secretion-specific mRNA. The Kpn deletion removes the normal site of cleavage and poly(A) addition, and it is possible that it is the absence of this site which changes the processing pattern. Alternatively, it is possible that sequences absent in the Kpn deletion but present in the BAL deletion function in regulating the production of predominantly secretion-specific mRNA in myeloma cells. The possible role of a highly conserved sequence found in this region is discussed. PMID- 2878364 TI - A single amino acid substitution in v-erbB confers a thermolabile phenotype to ts167 avian erythroblastosis virus-transformed erythroid cells. AB - A library of recombinant bacteriophage was prepared from ts167 avian erythroblastosis virus-transformed erythroid precursor cells (HD6), and integrated proviruses from three distinct genomic loci were isolated. A subclone of one of these proviruses (pAEV1) was shown to confer temperature-sensitive release from transformation of erythroid precursor cells in vitro. The predicted amino acid sequence of the v-erbB polypeptide from the mutant had a single amino acid change when compared with the wild-type parental virus. When the wild-type amino acid was introduced into the temperature-sensitive avian erythroblastosis virus provirus in pAEV1, all erythroid clones produced in vitro were phenotypically wild type. The mutation is a change from a histidine to an aspartic acid in the temperature-sensitive v-erbB polypeptide. It is located in the center of the tyrosine-specific protein kinase domain and corresponds to amino acid position 826 of the human epidermal growth factor receptor sequence. PMID- 2878366 TI - Tropical spastic paraparesis: HTLV-I antibodies in patients from the Seychelles. PMID- 2878363 TI - p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity. AB - The neu oncogene was originally identified in cell lines derived from rat neuroectodermal tumors. neu is related to but distinct from the c-erbB gene, which encodes the epidermal growth factor (EGF) receptor. neu encodes a protein, designated p185, that is serologically related to the EGF receptor. Identification of the normal homolog of p185 encoded by the neu proto-oncogene enabled us to compare the product of the neu proto-oncogene with the mutated version specified by the neu oncogene and with the EGF receptor. The normal form of p185 was structurally similar to its transforming counterpart, indicating that activation of the neu oncogene did not cause major structural alterations in the gene product. Both normal and transforming forms of p185 were associated with tyrosine kinase activity, supporting the idea that normal p185 functions as a growth factor receptor. p185 differed both structurally and functionally from the EGF receptor. p185 and the EGF receptor had distinct electrophoretic mobilities when synthesized under normal culture conditions or in the presence of tunicamycin. EGF did not stimulate increased turnover of p185 and did not bind quantitatively to p185. A number of other growth factors failed to stimulate degradation of p185 or tyrosine phosphorylation of p185 and are therefore unlikely to be ligands for p185. PMID- 2878367 TI - Cancer chemotherapy. Progress in understanding multidrug resistance. PMID- 2878365 TI - Characterization of two atypical promoters and alternate mRNA processing in the mouse Thy-1.2 glycoprotein gene. AB - The promoter and 5' flanking region of the mouse Thy-1.2 glycoprotein gene were characterized by DNA sequencing, primer extension analysis, and deletion analysis. Transcriptional initiation sites were identified which corresponded to two separate exons upstream of the portion of the gene encoding the Thy-1.2 glycoprotein. We demonstrated that the mouse Thy-1.2 gene was transcribed from two atypical promoters separated by 260 base pairs in the genomic sequence. These promoters contained neither TATAAG nor GGPyCCAATCT homologous sequences but defined a conserved nonamer CTCCCTGCT at -48 from each initiation site. Two Thy 1.2 mRNA species of 1,835 and 1,939 nucleotides, differing in the 5' untranslated region of the mRNA, were thus transcribed from the single Thy-1.2 gene by mRNA splicing to the same downstream exon. Recombinant genomes in which the bacterial chloramphenicol acetyltransferase gene was expressed from either of the two Thy 1.2 promoters demonstrated that each promoter functioned independently and did not direct cell-specific expression in lymphoid cells. The 5' flanking region of the Thy-1.2 gene upstream of -68 could be eliminated without altering cell-type specific expression. This suggests that regulatory elements responsible for tissue and developmental stage-specific expression of the Thy-1.2 gene are not present in the 5' flanking DNA but may reside downstream of the promoters. PMID- 2878368 TI - Homology between P-glycoprotein and a bacterial haemolysin transport protein suggests a model for multidrug resistance. AB - Increased expression of P-glycoprotein, a plasma membrane glycoprotein of relative molecular mass (Mr) 170,000 (170K), occurs in a wide variety of cell lines that exhibit pleiotropic resistance to unrelated drugs. The presence of P glycoprotein in human cancers refractory to chemotherapy suggests that tumour cells with multidrug resistance can arise during malignant progression. We have discovered striking homology between P-glycoprotein and the HlyB protein, a 66K Escherichia coli membrane protein required for the export of haemolysin (protein of Mr 107K). P-glycoprotein can be viewed as a tandem duplication of the HlyB protein. The hydropathy profiles of the two proteins are similar and reveal an extensive transmembrane region resembling those found in pore-forming plasma membrane proteins. The C-terminal region of P-glycoprotein and the HlyB protein contain sequences homologous to the nucleotide-binding domains of a group of closely related bacterial ATP-binding proteins. We propose a model for multidrug resistance in which P-glycoprotein functions as an energy-dependent export pump to reduce intracellular levels of anticancer drugs. PMID- 2878369 TI - A molecular gradient in early Drosophila embryos and its role in specifying the body pattern. AB - After fertilization, the protein products of the Drosophila homeobox gene caudal (cad) accumulate in a concentration gradient spanning the anteroposterior axis of the developing embryo. Mutations in the cad gene that reduce or eliminate the gradient cause abnormal zygotic expression of at least one segmentation gene (fushi tarazu) and alter the global body pattern. PMID- 2878370 TI - Cholinergic neurones acquire adrenergic neurotransmitters when transplanted into an embryo. AB - During development, cells become progressively restricted, until they reach their final phenotype. Differentiation was originally thought to be irreversible, but phenotypic plasticity has been observed in a variety of cell types, for example sympathetic neurones, the limb blastema and some glial cell types. A detailed description of the individual steps that lead to expression or reversal of phenotype is essential to understand the molecular events underlying cell differentiation. We examined whether ciliary neurones acquire adrenergic properties when exposed to a permissive embryonic environment. Cholinergic neurones were selectively labelled with a retrogradely transported marker and injected into chick embryos during active neural crest migration. Four to five days after injection, some of the labelled neurones were found in 'adrenergic sites' and had developed catecholamine histofluorescence. The cells had thus accumulated adrenergic neurotransmitters even after differentiation into cholinergic neurones. This result shows that neurotransmitter plasticity occurs in cholinergic neurones and suggests that the neurotransmitter phenotype can be modified by the embryonic environment. PMID- 2878371 TI - The correct activation of Antennapedia and bithorax complex genes requires the fushi tarazu gene. AB - In the Drosophila embryo the establishment and specification of metameric units depends upon the selective activation of the segmentation and the homoeotic selector genes. The former are necessary for establishing the appropriate number of metameric or parasegmental units, whereas the latter control the pathways of differentiation followed by particular parasegments. Classical embryological manipulations have show n that these processes must be closely coordinated during normal development. However, previous studies of pair-rule genes have led to the suggestion that the specification of segmental identity proceeds independently of the establishment of metameres as physical units. These apparently conflicting perspectives can be reconciled by envisaging a common maternally derived positional information system which is independently interpreted by the components of both processes. In the case of the partitioning process, the gap and pair-rule genes would be instrumental in translating this information, whereas the activation of the homeotic genes would be mediated via other intermediaries (see ref. 9 for review). It is difficult to see, however, how such a system could ensure the precise regulation of the tw o types of genes implicit in the final differentiated pattern. This difficulty has led to the suggestion that the segmentation mechanism must define the precise boundaries of selector gene expression. Here we confirm this suggestion and propose that the gene fushi tarazu plays a key role in this process, integrating the processes of metameric partitioning and regional specification in the Drosophila embryo. PMID- 2878372 TI - Effect of alpha-adrenoceptor agonists and antagonists on cholinergic transmission in guinea-pig isolated atria. AB - Evidence was sought for the existence on cholinergic nerve terminals in guinea pig atria of alpha-adrenoceptors subserving inhibition of acetylcholine release. The experiments were performed with atria which had been incubated with 3H choline and transmitter release was deduced from the efflux of radioactivity elicited by field stimulation. In preparations which had been incubated with 3H choline, field stimulation (60 pulses, 2 Hz) evoked release and radioactivity which was inhibited by 1.0 mumol/l noradrenaline, in the presence of propranolol (1.0 mumol/l), but was unaltered by clonidine (1.0 and 10.0 mumol/l). The inhibitory effect noradrenaline on the stimulation-induced efflux of radioactivity was blocked by idazoxan (0.3 mumol/l), and phentolamine (1.0 mumol/l) but not by prazosin (0.3 mumol/l). In the presence of propranolol (1.0 mumol/l), neither phentolamine (1.0 mumol/l), idazoxan (0.3 mumol/l) nor prazosin (0.3 mumol/l) had any effect on stimulation-induced efflux of radioactivity. Stimulation of the extrinsic vagus nerve of atrial preparations with trains of pulses at frequencies of 2, 4, 8, and 16 Hz produced graded decreases in the rate of atrial beating. The negative chronotropic responses to vagus stimulation were unaffected by noradrenaline (1.0 mumol/l) in the presence of propranolol (1.0 mumol/l). These findings indicate that the release of acetylcholine from the cholinergic terminals in guinea-pig atria can be inhibited by a mechanism apparently involving prejunctional alpha 2-adrenoceptors. However, under the experimental conditions used here the chronotropic responses of atria to stimulation of the extrinsic vagus nerve was not affected by activation of the prejunctional alpha 2-adrenoceptors associated with the cholinergic terminals. PMID- 2878373 TI - Blockade of alpha 2-adrenoceptors permits the operation of otherwise silent opioid kappa-receptors at the sympathetic axons of rabbit jejunal arteries. AB - We sought for presynaptic, release-inhibiting opioid receptors at the postganglionic sympathetic axons innervating the jejunal arteries of rabbits. Evoked excitatory junction potentials (e.j.p.s; trains of 15 pulses at 1 Hz) as well as evoked overflow of tritium after preincubation with [3H]-noradrenaline (trains of 120 pulses at 1 Hz) were used to estimate transmitter release. In otherwise untreated tissues ethylketocyclazocine reduced neither the e.j.p. amplitudes nor the evoked overflow of tritium; [Met5]-enkephalin depressed the evoked overflow of tritium. Ethylketocyclazocine reduced e.j.p. amplitudes, however, in tissues exposed to either yohimbine, tolazoline or phentolamine, but not in tissues exposed to prazosin. Ethylketocyclazocine also depressed the evoked overflow of tritium when yohimbine was present. The inhibition produced by ethylketocyclazocine in the presence of yohimbine was antagonized by (-)-3 furylmethyl)-alpha-noretazocine (MR 2266) but not by N,N-diallyl-Tyr-alpha aminoisobutyric acid-alpha-aminoisobutyric acid-Phe-Leu-OH (ICI 174864). It is concluded that the sympathetic neurones of rabbit jejunal arteries possess presynaptic kappa-receptors in addition to the previously identified delta receptors. The kappa-receptors become operative only when presynaptic alpha 2 adrenoceptors have been blocked. PMID- 2878376 TI - [Bronchodilators: beta-sympathicomimetics]. PMID- 2878374 TI - 3-Methoxytyramine accumulation: effects of typical neuroleptics and various atypical compounds. AB - The accumulation of 3-methoxytyramine (3-MT), the O-methylated metabolite of dopamine (DA), in rat striatum was used to assess the effects of drugs on dopaminergic activity. This was accomplished by pretreating rats with pargyline to completely inhibit 3-MT catabolism. Under the conditions used, 3-MT accumulation was linear over time for at least 90 minutes. Apomorphine and gamma butyrolactone, drugs which depress the activity of DA-containing neurons, decreased striatal 3-MT accumulation; whereas typical neuroleptics (haloperidol, fluphenazine, chlorpromazine), which increase the activity of DA-containing neurons, increased striatal 3-MT accumulation. In addition, a number of other drugs which block DA receptors and exert various atypical actions on dopaminergic functioning were examined. These "atypical" compounds (clozapine, buspirone, molindone) also increased striatal 3-MT accumulation, but were generally less potent than the typical neuroleptics examined. Moreover, the potencies of the typical neuroleptics and "atypical" compounds that were tested appear to be somewhat related to their affinities for D-2 DA receptors, as measured by their abilities to displace 3H-spiperone from rat striatal membrane preparations. Interestingly, this relationship was less evident when NaCl was omitted from the 3H-spiperone binding assay buffer. The potential antipsychotic drugs, BW 234U and SCH 23390, were also investigated for their effects on 3-MT accumulation and 3H spiperone binding, and they were relatively inactive in both of these measures of dopaminergic activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878375 TI - Effects of antiarrhythmic drugs on the extraneuronal accumulation of isoprenaline in perfused rat hearts. AB - The effects of class I, II, III and IV antiarrhythmic drugs (as classified by Vaughan Williams 1974), tetrodotoxin and beta 2-adrenoceptor antagonists on the extraneuronal accumulation of isoprenaline were examined in isolated rat hearts perfused with 3H-isoprenaline (1 mumol/l) and tropolone (100 mumol/l) for 30 min at a constant flow rate (6.5 ml/min) at 40 degrees C. Quinidine (class I), verapamil (IV), diltiazem (IV), dilazep (IV), nifedipine (IV), tetrodotoxin and butoxamine, at a concentration of 10 mumol/l, significantly decreased the extraneuronal accumulation of isoprenaline. The present study demonstrated that quinidine (class I) and all of the calcium channel blockers (class IV) had potent inhibitory effects on the extraneuronal accumulation of isoprenaline. The concentrations of these drugs needed for this decrease were nearly comparable to those needed to suppress isoprenaline-tropolone-induced ventricular fibrillation (Sono et al. 1985a). The antiarrhythmic effects of quinidine and calcium channel blockers in this experimental model may be partly due to a decrease in the extraneuronal accumulation of isoprenaline. PMID- 2878377 TI - Royal College of Nursing. Vital role. PMID- 2878378 TI - [Brain abscess: surgical or conservative treatment?]. PMID- 2878379 TI - Behavioral changes persisting into adulthood after neonatal benzodiazepine administration in the rat. AB - The day after birth male pups of hooded Lister rats were randomly fostered to form experimental litters of eight. Within each litter pups were randomly assigned among the following groups: vehicle control; diazepam (1, 5 or 10 mg/kg); lorazepam (0.25, 0.5, 1 or 2.5 mg/kg). Injections were given daily from day 1 until weaning at day 21. The pups were then tested as adults, from day 65. There were no effects of neonatal treatment when the pups were tested undrugged in 3 animal tests of anxiety, but in the social interaction test the neonatal diazepam treatment significantly reduced the anxiogenic effects of yohimbine. The neonatal diazepam treatment significantly enhanced the sedative effects of a challenge dose of chlordiazepoxide in the holeboard. Passive avoidance acquisition and retention were unaffected by the early treatment. Neonatal treatment with both benzodiazepines reduced the incidence of myoclonic jerks when the pups were challenged with pentylenetetrazole. Both neonatal treatments enhanced aggressive acts displayed when the residents were confronted with an intruder in their home-cages. However, when the rats that had been treated neonatally with lorazepam were themselves intruding into another's territory, they were significantly more submissive. PMID- 2878380 TI - Postmortem changes in the enzymes of GABA and glutamate metabolism in the cerebellum and forebrain of newborn and adult rats. AB - Postmortem changes in the activity of GDH, GAD, GABA-T, and GS in the adult forebrain and cerebellum and in the forebrain of newborns have been investigated. The activities of GDH, GAD, and GS were stable till 12 hr after death in both adult and young brain regions studied. The activity of GABA-T was stable till 30 min postmortem, but declined progressively thereafter in both regions in adult, as well as in young forebrain. PMID- 2878381 TI - Genetic determination of striatal tyrosine hydroxylase activity in mice. AB - An additive major gene effect is described for tyrosine hydroxylase activity in mouse corpus striatum (CS). Quantitative genetic analysis indicated the presence of a segregating Mendelian factor with robust additive effect in F2 generations derived from crossing two highly inbred mouse strains, C57BL/6ByJ and BALB/cJ, with intermediate (INT) and high (HI) TH activity in CS. Significant positive correlation was found between striatal and mesencephalic TH activity in the segregating generations, raising the possibility that a common single gene may express its effect through pleiotropy or linkage. Genetic preparations taking advantage of the major gene effect should serve well as animal models of DA mediated neuropsychiatric disorders. PMID- 2878382 TI - Choline and ethanolamine phosphotransferase activities in glomerular particles isolated from bovine cerebellar cortex. AB - Isolated cerebellar glomeruli provide a relatively homogeneous subcellular fraction, which can be used to study the biochemical events related to chemical transmission within a well-characterized central synapse. Choline and ethanolamine phosphotransferase activities were identified and partially characterized in this nerve ending preparation. Choline phosphotransferase associated with the glomerular particles required Mg2+, while ethanolamine phosphotransferase required Mn2+ for optimal activities. Both enzymes were inhibited by exogenous Ca2+. The apparent Vmax values were 35.9 and 10.0 nmol/hr per mg protein for the choline and ethanolamine phosphotransferases, respectively. The apparent Km value for the CDPcholine substrate was 28.6 microM, and the Km for CDPethanolamine was 8.3 microM. Neither enzyme responded to the various adenine nucleotides, neurotransmitters or neurotransmitter agonists tested. However, exposure of the glomerular particles to cytidine nucleotides inhibited ethanolamine phosphotransferase activity and stimulated choline phosphotransferase activity. PMID- 2878383 TI - Differential production of SRIF 14 and 28 by fetal rat hypothalamic cells enriched by velocity sedimentation. AB - Dispersed day-17 fetal rat hypothalamic cells have been enriched according to size by velocity sedimentation prior to culture, and the SRIF production by these enriched populations was compared with that of other enriched cell fractions and with mixed-cell cultures. Cultures of mixed cells produced 100-400 pg SRIF/10(6) cells/4 h over a period of 28 days. Total SRIF production by mixed cells was inversely proportional to seeding density over the range 0.25-1 X 10(6) cells/ml/well and SRIF 14 and 28 were secreted in a ratio of approximately 6:1. Although secretory rates by low cell densities remained higher than those by high cell densities, SRIF production decreased with time at all seeding densities (up to 21 days). Dispersed fetal hypothalamic cells were enriched according to size by allowing them to sediment over 4 h through a shallow gradient of BSA in culture medium and subsequent cell fractions developed widely differing morphologies in monolayer cultures. In contrast to mixed-cell cultures, SRIF production at 8 days by both large and small cells were directly proportional to initial seeding density. Furthermore, the smaller cells secreted very much less SRIF than the larger cells (100 pg/10(6) cells/4 h vs. 1,300 pg/10(6) cells/4 h), whereas there was little difference in overall SRIF content (350 pg/10(6) cells vs. 400 pg/10(6) cells). Characterisation by HPLC of the SRIF content and secretion of smaller cells revealed SRIF 14 to 28 ratios of 7:1 and 3:1, respectively. In contrast in the large cells, the ratio was 1:1 for both content and secretion. Therefore, these cell groups contain and secrete different proportions of these 2 molecular forms of SRIF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878384 TI - Histaminergic stimulation of prolactin secretion mediated via H1- or H2 receptors: dependence on routes of administration. AB - Controversy exists regarding the involvement of H1- or H2-receptors in the PRL releasing activity of histamine (HA). This could be due to differences in the route of administration of HA and histaminergic compounds. Therefore, we studied the effect on PRL secretion of HA and HA-agonists infused intracerebroventricularly (ICV) or systemically (IA) either alone or in combination with HA-antagonists in male rats. HA administered ICV as well as IA stimulated PRL secretion dose dependently. The stimulatory effect of ICV-infused HA was blocked by the H2-receptor antagonist cimetidine (CIM) and mimicked by the H2-receptor agonists 4-methylhistamine (4-MeHA) and dimaprit (DIM). In contrast, the H1-receptor antagonist mepyramine (MEP) enhanced the PRL-releasing effect of HA while the H1-receptor agonist 2-thiazolylethylamine (2-TEA) had no significant effect. The stimulatory effect of IA-infused HA was blocked by the H1-receptor antagonist MEP and mimicked by the H1-receptor agonist 2-TEA, whereas the H2 receptor antagonist CIM enhanced the PRL-stimulatory effect of HA and the H2 receptor agonist DIM was without effect. 4-MeHA stimulated PRL secretion, but this effect was unrelated to stimulation of H2-receptors. The effect of ICV administered HA was unaffected by IA infused antagonists and the effect of IA administered HA was not altered by ICV infused antagonists. HA had no effect on the PRL release from isolated adenohypophyses, and HA did not stimulate PRL secretion in pituitary stalk-sectioned rats following IA infusion. The findings indicate that HA administered ICV exerts its PRL releasing activity via H2 receptors while HA administered IA stimulates PRL secretion via H1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878386 TI - On the presence of a nondopaminergic, peptidergic prolactin release-inhibiting factor in hypothalamic extracts of infantile rats. AB - Crude hypothalamic extracts prepared from brains of 1-day-old rats produced a dose-dependent inhibition of prolactin (Prl) release by adult male hemipituitaries, and to a lesser extent by hemipituitaries of adult ovariectomized (OVX), estrogen-primed rats. These extracts contained 6-fold lower levels of dopamine than adult hypothalami. The inhibitory effect of the adult hypothalamic extracts, contrary to infantile hypothalamic extracts could be blocked by spiroperidol. Digestion of the infantile hypothalamic extracts with pronase totally abolished their Prl release-inhibiting activity, indicating the peptidic nature of this inhibitory substance. In contrast to their effect on Prl release by hemipituitaries, infantile hypothalamic extracts stimulated Prl release from dispersed anterior pituitary cells of OVX estrogen-primed rats, pointing to the importance of estrogen in modulating prolactin release-inhibiting factor (PIF) activity and the possibility that the PIF receptor is trypsin sensitive. PMID- 2878385 TI - Direct, neuronal action of atrial natriuretic factor in the rat brain. AB - The present investigation assessed the ability of atrial natriuretic factor (ANF) to affect hypothalamic neuronal excitability. Single neurons in the rostral septal-preoptic area of the female rat brain were recorded extracellularly and tested for responsiveness to iontophoretically applied and/or pressure-ejected ANF. Neurons responsive to ANF were detected in the lateral septal nucleus, the lateral paraolfactory area, the bed nucleus of the anterior commissure, and the medial preoptic area. The majority of neurons influenced by ANF (16 out of 18) exhibited a decrease in spontaneous firing rate during application of the peptide. In some cases, the inhibitory response outlasted the period of ANF application. When both iontophoretic and pressure ejection techniques were used to apply ANF to an individual neuron, the responses were similar. The results indicate that ANF is capable of modulating the membrane excitability of rat forebrain neurons and suggest that the peptide acts as a neuromodulator/neurotransmitter within the central nervous system. PMID- 2878387 TI - Influence of antipsychotics on presynaptic receptors modulating the release of dopamine in synaptosomes of the nucleus accumbens of rats. AB - The release of preloaded [3H]dopamine (DA) from superfused synaptosomes stimulated by 30 mM K+ was investigated in the nucleus accumbens of rats. Under conditions preventing the uptake of DA (presence of 40 microM cocaine) release of [3H]DA was inhibited by DA and apomorphine in a concentration-dependent manner (IC50s 0.65 and 0.3 microM, respectively). The maximal inhibitory effects of DA, as well as of apomorphine, were about 50% of the controls. The DA-induced inhibition was antagonized by antipsychotics completely; the rank order of antagonistic potencies was haloperidol greater than clozapine greater than sulpiride; methiothepine was ineffective. Furthermore, the K+-stimulated release of [3H]DA was inhibited by serotonin in a concentration-dependent manner (IC50 = 0.9 microM). This inhibitory effect was antagonized by methiothepine with a high efficiency, by clozapine and methysergide with moderate efficiencies; haloperidol and sulpiride were ineffective. The experimental system demonstrated appears to be suitable for characterizing the DA- and serotonin-antagonistic potencies of antipsychotics and other drugs on presynaptic autoreceptors as well as receptors modulating release of DA in the nucleus accumbens. PMID- 2878388 TI - Behavioral effects of centrally administered dynorphin and [D-ala2-D-leu] enkephalin (DADLE) in rats. AB - Dynorphin and [D-ala2-D-leu]enkephalin (DADLE) were administered directly into the cerebrolateral ventricles of rats and effects on various indices of sensorimotor function and retention of a passive avoidance task were measured. Dynorphin markedly suppressed exploratory motor activity and decreased responsiveness to an acoustic stimulus. Although increases in latency to respond to a noxious thermal stimulus were seen in rats after dynorphin, these changes were always associated with alterations in motor capacity. Injection of dynorphin immediately after a passive avoidance training trial had no significant effect on retention 1 week later. The physiological effects of DADLE were clearly different than those of dynorphin. DADLE produced a biphasic decrease followed by an increase in motor activity and an increased acoustic startle reactivity. DADLE had no effect on reactivity to a noxious thermal stimulus. Posttrial administration of DADLE significantly impaired retention of a step-through passive avoidance task 1 week after training. These data indicate different neurobiological roles for kappa and delta opiate receptors in the central nervous system. PMID- 2878389 TI - Effects of temazepam on sleep quality and subsequent mental efficiency under normal sleeping conditions and following delayed sleep onset. AB - A group of 24 healthy, normal sleepers participated in 2 experiments. The 1st experiment was designed to investigate the effects of 2 nocte doses of temazepam on subjective sleep quality and performance next morning. In contrast to placebo or no-capsule conditions both temazepam 10 and 20 mg improved a number of assessments of sleep quality, although no residual effects on performance were detected. The 2nd experiment was designed to study the effects of temazepam 20 mg on daytime sleeping and subsequent performance following a simulated night shift. Compared to placebo, temazepam had favourable effects on the subjective duration and quality of daytime sleep, but had no overall beneficial or detrimental residual effects on performance. PMID- 2878390 TI - An analysis of the effects of excitatory amino acid receptor antagonists on evoked field potentials in the olfactory bulb. AB - The effects of excitatory amino acid antagonists on extracellular field potentials in the olfactory bulb produced by lateral olfactory tract stimulation were analysed in vivo. The compounds tested D-2-amino-5-phosphonovalerate, L-(+)2 amino-4-phosphonobutyrate, gamma-D-glutamylglycine, L-glutamic acid diethylester and cis-2,3-piperidine dicarboxylic acid, were administered by brain dialysis. Of the compounds tested, only cis-2,3 piperidine-dicarboxylic acid and gamma-D glutamylglycine were able to suppress the synaptic excitation of granule cells. This pharmacological profile suggests the involvement of non-N-methyl-D-aspartate receptors. However, the suppression was accompanied by a reduction in the amplitude of the presynaptic volley. A second finding was that D-2-amino-5 phosphono-valerate and gamma-D-glutamyl glycine attenuated granule cell mediated inhibition of mitral cells, suggesting the involvement of N-methyl-D-aspartate sensitive receptors. The possibility that mitral cells and that either centrifugal fibres, or an intrinsic olfactory bulb feedback loop might use an excitatory amino acid as its neurotransmitter is therefore discussed. PMID- 2878391 TI - Black widow spider venom-induced release of neurotransmitters: mammalian synaptosomes are stimulated by a unique venom component (alpha-latrotoxin), insect synaptosomes by multiple components. AB - Synaptosomes isolated from the rat brain corpus striatum and locust head and thoracic ganglia were loaded with radioactive neurotransmitter ([3H]dopamine and [3H]acetylcholine, respectively) and then treated with alpha-latrotoxin and other fractions (fractions C, D and E of Frontali et al.8) obtained by Sephadex G200 column chromatography from black widow spider venom gland homogenates. As shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, alpha-latrotoxin is a high Mr protein, whereas fractions C-E are mixtures of several proteins, that include small amounts of contaminating alpha-latrotoxin (especially in fraction C). In rat synaptosomes alpha-latrotoxin induced massive neurotransmitter release, and some release was induced also by high concentrations of fractions C and D. These responses were blocked almost completely by a monospecific anti-alpha-latrotoxin serum, indicating that they were all due to alpha-latrotoxin. Release of [3H]acetylcholine from locust synaptosomes was induced by the various preparations investigated. alpha Latrotoxin was about 10-fold less potent in locust than in rat synaptosomes. The effects of fractions C-E tended to disappear with storage. The most active batches of fractions C and E were even more potent than alpha-latrotoxin, while the D fraction was approximately 5-fold less potent. The anti-alpha-latrotoxin antiserum inhibited part of the responses elicited by fractions C and E, but left fraction D almost unaffected. Release by D and E fractions was maintained even when Ca2+ was removed from the incubation medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878392 TI - Carrier diagnosis of Duchenne muscular dystrophy using restriction fragment length polymorphisms. AB - Molecular probes that are tightly linked to and flank the Duchenne muscular dystrophy (DMD) locus, have been used to characterize DMD mutations and diagnose female carriers. Deletions within the Xp21 region were identified for 8 of 71 families studied. Using both DNA and CK studies, accurate (96 to 98%) carrier or noncarrier diagnoses were made for 51 of 75 females at risk in 24 families with a single affected male. DNA studies resulted in an alteration of predicted risk in 40% of the cases. Recombinant diagnostic methods are useful for carrier detection in families with one or more affected males. PMID- 2878393 TI - Peripheral neuropathy in systemic vasculitis: clinical and electrophysiologic study of 22 patients. AB - Twenty-two patients with evidence of systemic vasculitis and peripheral neuropathy were clinically and electrophysiologically investigated in a retrospective study. Ten had a polyarteritis nodosa, 6 a probable polyarteritis nodosa, and 6 a Churg-Strauss syndrome. Nine patients presented clinically with mononeuropathy or mononeuropathy multiplex considered typical of ischemic involvement of peripheral nerve; nine had more diffuse neuropathy, two of them a symmetric polyneuropathy. EMG examination revealed more diffuse neuropathy than clinically predicted. Findings were of acute or subacute axonal neuropathy. PMID- 2878394 TI - [Medullary carcinoma of the thyroid. Natural history, diagnosis and therapy]. PMID- 2878395 TI - Eseroline depresses the responses of dorsal horn neurons to C-fiber afferents in the spinal rat. AB - Eseroline not only has some structural features in common with morphine but also has a specific antinociceptive action like opioid drugs. The effects of eseroline on the responses of rat dorsal horn lamina V neurons to C-fiber-related noxious stimuli were investigated. The data obtained showed that 15 min after eseroline administration, the neuronal responses to C-fiber-related afferents were almost totally suppressed. Morphine was used as reference drug. The postulated action of eseroline on opioid receptors was confirmed by reversal of eseroline-driven cell activity after naloxone injection. PMID- 2878396 TI - Amygdaloid kindling increases enkephalin-like immunoreactivity but decreases dynorphin-A-like immunoreactivity in rat hippocampus. AB - The effects of amygdaloid kindling on the regional levels and distribution of enkephalin-like and dynorphin-A (DN)-like immunoreactivity (LI) were examined. One day after completion of kindling, radioimmunoassay revealed a 71% decrease in DN1-8-LI and a 43% increase in [Met5]-enkephalin-LI in the hippocampus. Immunostaining revealed a depletion of DN1-17-LI in the hippocampal mossy fiber pathway and an increase in [Leu5]-enkephalin-LI in the temporoammonic pathway. Four weeks after completion of kindling, the levels and immunostaining intensity of dynorphin and enkephalin in the hippocampus had returned to control values. PMID- 2878397 TI - Electrophysiological responses of human spinal neurons in culture. AB - Cell cultures were prepared from human fetal spinal cord and maintained in vitro for 30-100 days. Neurons were identified electrophysiologically by their ability to develop action potentials in response to intracellular depolarizing current pulses and in sister cultures by immunohistochemical and electron microscopic techniques. Extracellular applications of gamma-aminobutyric acid, glycine or histamine evoked hyperpolarizations which were associated with increases in membrane conductance. These data and the ultrastructural demonstrations of synapses suggest a functional differentiation of neurons in these cultures. PMID- 2878398 TI - D2 dopamine receptors associated with inhibition of dopamine release from rat neostriatum are independent of cyclic AMP. AB - The ability of the selective D2 dopamine (DA) receptor agonist bromocriptine to inhibit potassium-induced DA release from striatal slices was measured in rats, which had been unilaterally injected with kainic acid into the left striatum, with the aim of verifying whether the central nervous system contains DA receptors whose stimulation evokes intracellular events which do not involve cyclic AMP. It was found that increasing concentrations of bromocriptine inhibited the potassium-stimulated DA release from rat striatal slices of the kainic acid-treated side with the same potency as in control slices. On the contrary, bromocriptine and the selective D1 agonist SKF 82526 completely lost the ability to inhibit or stimulate, respectively, striatal adenylate cyclase activity from the lesioned side. Our conclusion asserts that inhibition of DA release from rat striatal slices is mediated by stimulation of D2 DA receptors which are fully operative in absence of both DA-stimulated and DA-inhibited adenylate cyclase activity. These data suggest that the intracellular events that follow D2 receptor stimulation in the nigrostriatal nerve terminals may be regulated by second messengers other than cyclic AMP. PMID- 2878399 TI - HR 375: a potential antipsychotic drug that interacts with dopamine D2 receptors and sigma-receptors in the brain. AB - The potential antipsychotic HR 375 (3-(4-(3-(4-fluorobenzoyl)-propyl-piperazino-1 yl-isoquinolino+ ++-hydrochloride) inhibited [3H]spiperone binding to dopamine D2 receptors and (+)-[3H]SKF-10047 binding to sigma-receptors. The drug was, however, almost inactive in phencyclidine and mu-, kappa- and delta-opioid receptor binding assays. HR 375 inhibited binding of (+)-[3H]SKF-10047 to sigma sites in a competitive manner. The dissociation constant of (+)-[3H]SKF-10047 binding to sigma-receptors was increased from 62 nM (47-91 nM) to 263 nM (204-370 nM) in the presence of 33 nM HR 375. The number of binding sites (Bmax) was, however, not affected. It is concluded that the pharmacological properties of HR 375, at least in part, may be attributable to its interaction with sigma receptors. PMID- 2878400 TI - The neurotoxicology of lead. AB - In the past six years, our research group has investigated the relationship between lead exposure and mental and behavioural development. This has been carried out through studies in children and animals. Earlier studies in children have shown that associations might be expected between environmental exposure to lead and various aspects of cognitive and behavioural development. Our study has examined and continues to examine, a cohort of children sub-divided into three groups according to the level of lead exposure during early 'in utero' development. Data amassed to date includes measurement of psychometric function and post natal development, together with biochemical measures of lead exposure. Assessment will continue through to early scholastic performance and will include measurement of deciduous tooth lead concentration as an integrated measure of long term exposure. In addition to these studies in children, a series of neurochemical studies have been carried out using a rat model of lead exposure. Data obtained from both our own neurochemical experiments and those of other groups indicate an extremely complex plethora of neurotoxic actions of lead. PMID- 2878401 TI - Central neurotransmitter disturbances underlying developmental neurotoxicological effects. AB - Transmission of information among neurons is of a chemical nature. The activity of the neurotransmitter in the brain is regulated by the spontaneous activity of neurotransmitter cell body and the sensitivity of both pre- and post-synaptic receptors. Neurotransmitters are present at very early stages of brain development; they do not only mediate the behavioral-physiological responses of the immature animal, but have trophic effects on the maturation of target neurons as well. Many centrally acting drugs which are frequently used also during pregnancy for the treatment of depression, hypertension, epilepsy, asthma, insomnia, hyperkinetism and other neurological and psychiatric disorders act directly on brain neurotransmitters (in particular monoamines) and behavioral states. Chronic administration of drugs acting on monoamines (such as clonidine, imipramine, alpha-methyl-Dopa, reserpine, monoamine oxidase inhibitors, diazepam) disturb the spontaneous activity and behavioral state dependency of the monoaminergic cells, influences neurotransmitter turnover and change the sensitivity of both pre- and post-synaptic receptors. Sensory deprivation during a critical period of development is known to produce permanent effect on the brain; e.g., monocular deprivation during a particular period of development in a kitten leads to a rewiring of the connectivity in the visual system in the adult cat. Disturbances in neurotransmitter activity during early life will induce a comparable reorganization of the chemical structure of the adult brain. PMID- 2878402 TI - Nutrition classics. Lipids, June 1979 Volume 14, No. 6: Reproduction and survival of rainbow trout (Salmo gairdneri) fed linolenic acid as the only source of essential fatty acids. By T.C. Yu, R.O. Sinnhuber, and J.D. Hendricks. PMID- 2878403 TI - Linolenate metabolism. PMID- 2878404 TI - OTC vs. Rx for coughs and colds. PMID- 2878405 TI - Dental phobia: a report of three cases. PMID- 2878406 TI - Guanylate cyclase activity in normal and neoplastic squamous epithelia from the upper aero-digestive tract. AB - Cyclic nucleotides (cAMP, cGMP) are suggested to participate in the regulation of cell growth and differentiation. Guanylate cyclase is the enzyme which catalyzes the synthesis of cGMP. The basal guanylate cyclase activity was slightly higher in well-differentiated squamous cell carcinomas than in normal mucosa, but was two-fold higher in papillomas. Poorly differentiated squamous cell carcinoma did not show any increased basal activity. Stimulation with nitroprusside (NP) resulted in a 20% increased activity for normal mucosa and a 30% increase for poorly differentiated carcinomas, whereas enzyme prepared from well differentiated squamous carcinomas and papillomas showed a two-fold increase. PMID- 2878408 TI - [Practical problems of prognosis in neuroleptic therapy]. PMID- 2878407 TI - [Management of undescended testis based on our studies]. PMID- 2878409 TI - Expired ipecac syrup efficacy. AB - A controlled prospective study to evaluate the efficacy of expired ipecac syrup was conducted at two regional poison control centers in New England. During a 6 month period, 200 study patients treated with expired ipecac syrup and 200 control patients treated with unexpired ipecac syrup were evaluated. There were no statistical differences between the control and study groups in patient characteristics (age and sex) and product characteristics (general class, emetic potential, pretreatment, previously opened bottles, and manufacturer). In both control and study groups, emesis occurred in 100% of cases with 90% of patients vomiting with the first dose. The mean time to emesis was 24.7 minutes and 24.8 minutes in the study and control groups, respectively. Expired preparations ranged from 1 month to greater than 4 years postexpiration, with the duration of expiration not altering the mean time to emesis. Mean time to emesis between the two groups was also not affected by manufacturer, pretreatment with milk, or whether the ipecac syrup bottle was previously opened. We conclude that expired ipecac syrup (up to 4 years postexpiration date) is an effective emetic. PMID- 2878410 TI - [Acute LAV/HTLV III infection]. PMID- 2878411 TI - Presence of an EcoRI RFLP of the c-mos locus in normal and tumor tissue of esophageal cancer patients. PMID- 2878412 TI - XhoI polymorphism at the human pronatriodilatin (hPND) gene locus. PMID- 2878413 TI - TaqI polymorphism at the 3' end of the human pronatriodilatin gene (hPND). PMID- 2878414 TI - A three-allele RFLP recognised by an anonymous sequence localized to 3p14-p21 [D3S11 (E41)]. PMID- 2878415 TI - DraI RFLP in the human apolipoprotein AI-CIII-AIV gene complex. PMID- 2878416 TI - Anonymous genomic fragment co-amplified with c-Ki-ras 2 detects frequent polymorphism (pK42). PMID- 2878417 TI - Linkage arrangement in the vitellogenin gene family of Xenopus laevis as revealed by gene segregation analysis. AB - Using restriction fragment length polymorphism (RFLP) we have analyzed the segregation of alleles of the different vitellogenin genes of Xenopus laevis. The results demonstrate that the four genes whose expression is controlled by oestrogen, form two linkage groups. The genes A1, A2 and B1 are linked genetically whereas the fourth gene, the gene B2, segregates independently. The possible origin of this unexpected arrangement is discussed. PMID- 2878418 TI - Human cDNA probe detects RFLP on chromosome 12, OL 202 (HGM8 designated no. D12S9). PMID- 2878419 TI - An EcoRI restriction fragment length polymorphism at the KRAS2 locus on mouse chromosome 6. PMID- 2878421 TI - Isolation of a polymorphic DNA sequence (lambda EMBL3.287, D8S8) from chromosome 8. PMID- 2878420 TI - Human atrial natriuretic peptides (ANP) gene locus: BglI RFLP. PMID- 2878422 TI - Isolation of a polymorphic DNA sequence (lambda EMBL3.121, D14S12) from chromosome 14. PMID- 2878423 TI - RFLP detected by an X-linked cDNA encoding erythroid-potentiating activity/tissue inhibitor of metalloproteinase (EPA/TIMP). PMID- 2878424 TI - [Abdominal form of Takayasu disease]. PMID- 2878425 TI - [Dynorphin as an analgesic for the dental pulp]. PMID- 2878426 TI - [Neuromediator changes during cerebral aging. The effect of Ginkgo biloba extract]. AB - Ginkgo biloba extract exerts a specific effect on the noradrenergic system and on beta-receptors. No variation was found in alpha 2-receptors and serotonin uptake. These findings provide the first evidence of central effects of a drug acting on cerebral ageing, connected specifically to reactivation of the noradrenergic system in the cerebral cortex. PMID- 2878428 TI - [Metabolic control of insulinoma with a prolonged-action somatostatin agonist]. PMID- 2878427 TI - [Neuromediator binding to receptors in the rat brain. The effect of chronic administration of Ginkgo biloba extract]. AB - The present data confirm the results of others that post-synaptic receptor changes may contribute to the decline in brain cholinergic function in ageing and dementia. We have also shown that chronic oral treatment with an extract of Gingko biloba increases the apparent muscarinic receptor population in the hippocampus of the aged Fisher 344 rat. The possible effect on (3H) kainic acid binding to the kainate-excitatory amino acid site is also interesting because of the proposed association of neurodegenerative disease and excessive excitatory amino neurotransmission. PMID- 2878430 TI - Developmental regulation of glutamine synthetase and carbonic anhydrase II in neural retina. AB - Glutamine synthetase (GS) is expressed in the neural retina only in Muller glia cells and is inducible with cortisol. A chicken genomic clone that contains at least part of the coding region for the GS enzyme was used to investigate developmental changes in the level of GS mRNA in embryonic chicken retina. A major GS transcript (approximately equal to 3 kilobases) detected by the probe begins to accumulate sharply on day 15 of embryonic development. When cortisol is prematurely supplied to early embryonic retina, it induces precocious accumulation of GS mRNA and of the GS enzyme. At later ages, these effects of cortisol are significantly greater, which suggests that competence to transcribe or stabilize GS mRNA in response to stimulation with cortisol increases with development. Carbonic anhydrase II (CA-II) is expressed in early retina in all the cells, but it becomes later restricted to Muller glia. Using cloned CA-II cDNA, we detected a high level of CA-II mRNA in early retina, followed by a decline due to arrest of CA-II mRNA accumulation in differentiated neurons. As glia cells mature, CA-II mRNA and the enzyme increase to a new high level. Therefore, changes in CA-II gene expression during retina development reflect differentiation-dependent cell-type-specific control of CA-II mRNA accumulation. PMID- 2878429 TI - Lipid requirements for reconstitution of the proton-translocating complex of clathrin-coated vesicles. AB - We have recently reported the reconstitution of the clathrin-coated vesicle proton-translocating complex with liposomes prepared from ethanol-extracted crude bovine brain lipids. Reconstitution of proton pumping by the isolated proton ATPase has now been achieved with liposomes prepared from pure lipids. Optimal proton pumping, as assessed by ATP-generated acridine orange quenching and 32Pi ATP exchange, is achieved with liposomes prepared from phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and cholesterol at a weight ratio of 40:26.5:7.5:26, and a lipid-to-protein weight ratio of 200:1. Under such conditions, the extent of decrease of ATP-generated acridine orange quenching is 150-fold greater than that of native clathrin-coated vesicles. Cholesterol is required to stabilize the proteoliposome. Phosphatidylserine, which is most effective in activating ATP-hydrolytic activity of the solubilized enzyme, is not obligatory for reconstitution of proton pumping. PMID- 2878433 TI - The susceptibility of Werner's syndrome and other human skin fibroblasts to SV40 induced transformation and immortalization. AB - In attempts to transform and immortalize human cell cultures, skin fibroblasts from normal donors of different ages, from patients with the premature ageing diseases Werner's syndrome (WS) and progeria (PR), and from donors with the cancer-prone diseases ataxia telangiectasia (AT), Bloom's syndrome (BS) and Fanconi's anaemia (FA), were infected with SV40 virus and their growth monitored thereafter. Lesch-Nyhan (LN) fibroblasts were also infected. SV40-infected cultures from two normal and from WS, AT and LN donors attained a spectrum of transformed properties, high mitotic activity at confluence, presence of T antigen, anchorage independence and altered morphology. Most of these pretransformed cultures died in the crisis period. However, two cultures from the WS and LN patients survived the crisis period and have now been grown to more than 200 passages. For the LN culture the crisis period was at least 200 days. Both permanent lines retain the properties of pretransformed cells, but differ in their modal chromosome number and ability to grow in methionine-free medium. It can be concluded from these experiments that transformation by SV40 to permanent lines is a rare event in human skin fibroblasts, even when these cells were taken from patients predisposed to form cancers. PMID- 2878432 TI - Cognate homeo-box loci mapped on homologous human and mouse chromosomes. AB - The homeotic genes of Drosophila, which regulate pattern formation during larval development, contain a 180-base-pair DNA sequence termed the "homeo-box." Nucleotide sequence comparisons indicate that the homeo-box motif is highly conserved in a variety of motazoan species. As in Drosophila, homeo-box sequences of mammalian species are expressed in a temporal and tissue-specific pattern during embryogenesis. These observations suggest functional homologies between dipteran and mammalian homeo-box gene products. To identify possible relationships between homeo-box genes of mice and humans, we have compared the chromosomal location of homeo-box genes in these species. Using in situ hybridization and somatic cell genetic techniques, we have mapped the chromosome 6-specific murine Hox-1 homolog to the region p14-p21 on human chromosome 7. We have also regionally mapped the murine Hox-3 locus to 15F1-3 and its human cognate to 12q11-q21. These comparative mapping data indicate that a syntenic relationship in mice and humans is maintained for all homeo-box loci examined to date. We suggest these regions represent evolutionarily conserved genomic domains encoding homologous protein products that function in regulating patterns of mammalian development. PMID- 2878431 TI - Use of nonisotopic M13 probes for genetic analysis: application to HLA class II loci. AB - Previously, DNA polymorphisms in the HLA gene cluster have been analyzed using radioactive probes in Southern blot experiments; the restriction fragment length polymorphisms (RFLPs) revealed by this analysis are capable of subdividing HLA serological types. Here, we report the use of DNA probes labeled with biotinylated psoralen to provide nonisotopic detection of HLA class II RFLP patterns. These biotinylated probes contain cDNA sequences encoding the alpha and beta chains of DP, DQ, and DR HLA class II genes as inserts in M13 vectors. The recombinant M13 molecules are partially double-stranded with single-stranded HLA cDNA regions and contain biotinylated psoralen covalently linked to duplex DNA by UV irradiation. Following hybridization, the presence of biotinylated probe bound to target DNA is detected using a streptavidin-horseradish peroxidase conjugate, which converts the colorless substrate 3,3',5,5'-tetramethylbenzidine to a blue precipitate in less than 1 hr. The probe and detection system described here can detect single-copy genes in less than 0.5 microgram of total human DNA on Southern blots and generates the same specific RFLP patterns as do probes labeled with 32P by nick-translation. These biotinylated HLA class II probes have been applied to tissue typing for bone marrow transplantation and the study of insulin dependent diabetes susceptibility, revealing in each case relevant polymorphisms not detected by serologic typing. PMID- 2878435 TI - Minimal latency of calcium release in frog twitch muscle fibres. AB - Intracellular release of calcium in frog skeletal muscle fibres was monitored by the use of arsenazo III, in response to voltage clamped depolarizing pulses. A latency of a few milliseconds was evident between the onset of depolarization and the first detectable rise in the arsenazo-calcium signal, and this decreased logarithmically as the depolarization was increased. The minimal latency with strong depolarization (to +20 to +100 mV) was about 2 ms at 5 degrees C. This delay appears to be sufficiently long to be compatible with a chemically mediated coupling mechanism between depolarization and calcium release from the sarcoplasmic reticulum. PMID- 2878434 TI - New observations on the substructure of the active zone of brain synapses and motor endplates. AB - This study offers a new concept on the origin and function of the hitherto enigmatic presynaptic dense projections (dps) of neurons and motor endplates. After a deuterium oxide-albumin pretreatment (da), brain tissue and motor endplate of rat and frog reveal an intricate association of smooth endoplasmic reticulum (ser), microtubules (mts) and synaptic vesicles (sv) at the presynaptic grid-active zone of synapses. The ser entwines the mts, which are clothed in svs, and impinges directly onto the presynaptic membrane as sacs or 'tubular fibrillar' extensions. Since no dps are seen in these sections, whereas they do occur in conventionally processed material (i.e. without da pretreatment), it is suggested that the dps of conventional material may, in part, originate from improperly fixed ser at these points. Thus for the first time we demonstrate an in vivo system of ser which, because its 'finger' processes come into intimate contact with the presynaptic membrane, may be implicated in Ca2+ ion translocation, presumably out of the presynaptic bulb. Since no such tubular ser has been demonstrated in what are claimed to be sophisticated techniques (i.e. high-speed slam-freezing-freeze substitution) the actual sophistication of such methods is questioned. PMID- 2878436 TI - Heligmosomoides polygyrus (Nematoda): the dynamics of primary and repeated infection in outbred mice. AB - The population dynamics of Heligmosomoides polygyrus were studied in outbred male MF1 mice subject either to primary or repeated experimental infection. Little variability in susceptibility was observed between mice, but heterogeneity increased with both duration and intensity of primary infection; this result indicates that there are differences in parasite survival between hosts. The rate of parasite-induced host mortality was 4 X 10(-4) per parasite per host per parasite lifespan. The mortality rates of male and female larvae during their development in the intestinal wall were estimated as 0.033 and 0.021 per parasite per day respectively, and estimates of the expected lifespans of the adult male and female parasites in primary infection of 11.22 and 9.92 weeks were obtained. Approximately 40% of female worms were observed in copula at any one time, although this proportion was significantly depressed in hosts harbouring fewer than 50 parasites and during the first four weeks of infection. Parasite fecundity was markedly age-dependent; each female worm produced approximately 31,000 eggs during its lifespan. No density dependence in either worm survival or fecundity in primary infection was apparent. The only detectable effect of worm density was in association with spatial distribution in the intestine; high levels of infection were associated with a posterior shift in the location of a proportion of the parasite population. Characterization of the dynamics of primary infection allowed predictions to be made about the expected dynamics of repeated infection. The comparison of predicted results and observed data revealed unequivocal epidemiological evidence for the density-dependent regulation of parasite population growth during repeated infection, affecting both parasite survival and parasite fecundity. The results also demonstrated the existence of two types of host individual in which the dynamics of repeated infection were markedly different. It is concluded that immunological differences between mice (possibly under genetic control) may be responsible for the observed effects; approximately 25% of MF1 mice seem unable to generate any protective immunity against H. polygyrus, whereas 75% become almost completely refractory to reinfection. This experimental system could be used for quantitative investigation of the impact of acquired immunity and genetic heterogeneity on helminth population dynamics. Both are of obvious relevance with respect to the control of infections of medical and veterinary significance. PMID- 2878437 TI - Heligmosomoides polygyrus (Nematoda): the influence of dietary protein on the dynamics of repeated infection. AB - The influence of the protein component in the diet of the host on the population dynamics of gastrointestinal helminth infection was studied by using a mouse-H. polygyrus experimental model. Mice fed a 2% (by mass) protein diet ad libitum maintained body weight during the experiment, but gained weight steadily when fed a diet containing 8% (by mass) protein. When repeatedly infected with 5, 10, 20 or 40 larvae every 2 weeks, the mice fed the 2% (by mass) protein diet accumulated adult worms in direct proportion to exposure to the infective stages. Under similar infection regimes, mice fed an 8% (by mass) protein diet acquired a partly effective immunity to reinfection by the nematode. Acquired immunity was principally manifest as a reduction in the survival of adult worms, although a slight increase in the mortality rate and/or the development time of the tissue dwelling larval phase was observed. Worm fecundity per head was significantly depressed in hosts fed the 8% protein diet. In conclusion, in these experiments it is demonstrated that the nutritional status of the host can influence the population dynamics of helminth infection. PMID- 2878439 TI - A transmission delay and the effect of temperature at the triadic junction of skeletal muscle. AB - The coupling process at the triadic junctions in skeletal muscle fibres is characterized by a significant latency between the depolarization of the transverse tubular membrane and the release of Ca from the sarcoplasmic reticulum. This time interval, the triadic delay, is sufficiently long to allow for the participation of a chemical process. The strong temperature dependence of the triadic delay (Q10 near 2.7) suggests that a sequence of chemical steps may link the electrical signal in the T-tubules to the opening of Ca channels in the terminal cisternae of the sarcoplasmic reticulum. PMID- 2878438 TI - The dynamics of the interaction between myosin subfragment 1 and pyrene-labelled thin filaments, from rabbit skeletal muscle. AB - We have used actin labelled in Cys-374 with N-(1-pyrenyl)iodoacetamide to monitor the dynamics and equilibria of the interaction between myosin subfragment 1 and the actin-troponin-tropomyosin complex in the presence of calcium. These results are compared with those obtained for pure actin and myosin subfragment 1. The sensitivity of this fluorescent label allowed us to measure the binding affinity of myosin subfragment 1 for actin directly by fluorescence titration. The affinity of subfragment 1 for actin is increased sixfold by troponin-tropomyosin in the presence of calcium. Kinetic studies of the interaction of subfragment 1 and actin have revealed an isomerization of the actin-subfragment 1 complex from a state in which actin is weakly bound (Ka = 5.9 X 10(4) M-1) to a more tightly bound complex (Ka = 1.7 X 10(7) M-1) (Coates, Criddle & Geeves (1985) Biochem. J. 232, 351). Results in the presence of troponin-tropomyosin show the same isomerization. The sixfold increase in affinity of subfragment 1 for actin is shown to be due to a decrease in the rate of dissociation of actin from the weakly bound complex. PMID- 2878440 TI - New directions in antihypertensive drug therapy. PMID- 2878441 TI - Nutritional and functional requirements for essential fatty acids. PMID- 2878442 TI - Biphasic effects of MIF-1 and Tyr-MIF-1 on apomorphine-induced stereotypy in rats. AB - The effects of several doses of MIF-1 and Tyr-MIF-1 (0.2, 0.5, 1.0 and 5.0 mg/kg, SC) on the stereotypic behavior induced by various doses (0.08, 0.2, 0.5, 1.0 and 2.0 mg/kg, SC) of apomorphine (APO) were tested in rats. MIF-1 increased the stereotypic behavior induced by 0.5 and 1.0 mg/kg of APO, but decreased the stereotypic behavior induced by 2.0 mg/kg of APO. Tyr-MIF-1 showed a biphasic effect similar to that exerted by MIF-1. The results suggest that the type of response to MIF-1 and Tyr-MIF-1 after APO is influenced by the activity of central dopaminergic neurons. PMID- 2878443 TI - Changes in brain catecholamine mechanisms following perinatal exposure to marihuana. AB - Adult female rats received daily oral doses of a crude marihuana extract (CME; equivalent to 20 mg/kg delta 9-THC) throughout gestation and lactation. The offspring were sacrificed at 10, 20, 40 or 60 days postpartum and tissue samples of cerebral cortex and striatum were dissected and assayed for alpha 1-adrenergic and D2-dopaminergic receptors, respectively, and tyrosine hydroxylase activity. The body weight at birth and 10 days of age was reduced as was brain weight at 10 and 60 days of age in offspring exposed to CME. Perinatal exposure to CME reduced the binding capacity (Bmax) of D2 receptors in the striatum of 10 and 20-day-old offspring. The Bmax for alpha 1 receptors in the cerebral cortex was not altered at any age. Tyrosine hydroxylase activity was significantly decreased in the striatum of 20 and 40-day-old offspring exposed to CME. The results indicate that chronic perinatal exposure to CME can selectively alter the development of specific catecholamine mechanisms in rat brain. PMID- 2878444 TI - Effects of cold-restraint stress on gastric ulceration and motility in rats. AB - The effects of stress by restraint at 4 degrees C for 2 hr and of drug treatment on gastric lesion formation and motor activities (contraction frequency, amplitude and tone) were studied in rats. Restraint at room temperature (22 degrees C) produced a small ulcer index in the controls and did not significantly affect gastric motor activities; atropine and verapamil reduced but bethanechol increased gastric contractions under the same experimental conditions. Restraint at 4 degrees C markedly elevated the ulcer index. The frequency of gastric contractions was significantly increased in the first hr but the amplitude was depressed during the whole 2-hr observation period. Gastric tone initially fell but rose in the second hr of cold-restraint stress. Atropine and verapamil pretreatment prevented stress-induced ulcer formation and suppressed the frequency and amplitude of gastric contraction. Bethanechol stimulated both frequency and amplitude without significantly influencing stress ulcer size. It is unlikely that gastric hypermotility plays a major role in stress ulceration; the stomach smooth muscle-relaxing action of atropine and verapamil may contribute only partly to their antiulcer effects. PMID- 2878445 TI - Spontaneous chewing movements in rats during acute and chronic antipsychotic drug administration. AB - Single intraperitoneal doses of various antipsychotic drugs (clozapine 6, 12, 25 mg/kg, sulpiride 100 mg/kg, haloperidol 0.5, 1.0, 2.0 mg/kg, fluphenazine 0.5, 1.0, 2.0 mg/kg) induced a depression of the spontaneous chewing movement (SCM) rate in rats during the first 6-8 hours. Haloperidol and fluphenazine elicited a rebound increase in SCM on day 2-5, while clozapine and sulpiride did not. Atropine (5 mg/kg) reduced the SCM rate. During chronic administration for 10 months clozapine (50 mg/kg/day) caused no changes in the SCM rate. Sulpiride (120 mg/kg/day) gave a marginal rise above control levels, while thioridazine (40 mg/kg/day), chlorpromazine (30 mg/kg/day), fluphenazine (0.6 mg/kg/day) and haloperidol (0.4 mg/kg/day) produced highly significant increases in SCM rates. It is suggested that the present animal model may prove useful for monitoring the risk of tardive dyskinesia with individual drugs. PMID- 2878446 TI - Stimulatory effect of N-methyl aspartate on locomotor activity and transmitter release from rat nucleus accumbens. AB - N-Methyl-aspartate (NMA), an agonist at central glutamate receptors, elicited prolonged and intense locomotor activity when injected into the nucleus accumbens septi (NAS) in subconvulsive doses (3-10 micrograms bilaterally). This effect was antagonised by intra-accumbens injection of the specific NMA antagonist, aminophosphonovaleric acid (APV) in a dose (3.0 micrograms bilaterally) that was without intrinsic effect when given on its own. Intra-accumbens injection of APV also suppressed locomotor hyperactivity elicited by intra-accumbens injection of DA (50 micrograms bilaterally) in rats pretreated with nialamide. In vitro release of [3H]-acetylcholine in accumbens tissue slices was significantly increased in the presence of NMA (30 microM) or N-methyl-D-aspartate (NMDA) (15 microM). Both effects were antagonised by APV (30 microM). Similar results were obtained with tissue slices of rat corpus striatum. These results suggest that locomotor stimulation by intra-accumbens NMA is mediated by an action on the mesolimbic dopaminergic neuron, either directly or via a cholinergic interneuron. In addition, activity at the glutamate synapse may be enhanced by the presence of DA affecting glutamate release and/or reuptake. PMID- 2878447 TI - Ribulose biphosphate carboxylase-oxygenase. PMID- 2878449 TI - Structural studies of Rubisco from tobacco. AB - An electron density map of ribulose 1,5-bisphosphate carboxylase-oxygenase (Rubisco) from tobacco (Nicotiana tabacum) has been obtained by X-ray crystallography at a nominal resolution of 0.34 nm. Phases were determined by multiple isomorphous replacement with three heavy atom derivatives and then refined by solvent flattening. Rubisco is barrel-shaped, and has (422) symmetry. The fourfold axis runs down an open central channel, concentric with the barrel. The molecule measures 10.5 nm along the fourfold axis, and has a diameter of 13 nm perpendicular to the fourfold axis at the widest point. The diameter of the central channel is 2.8 nm at the centre of the molecule, and 0.6 nm at its narrowest constriction. Portions of the polypeptide backbone of the promoter have been traced and some 127 residues have been assigned to 14 alpha-helices. The amino acid sequences of Rubisco from Rhodospirillum rubrum and from the large subunit of tobacco are sufficiently similar to suggest that the two chains are folded in the same general way. PMID- 2878451 TI - [Validity of post-proline splitting dipeptidyl aminopeptidase activities in the cerebrospinal fluid for neurologic and psychiatric diagnosis]. AB - The dipeptidyl-peptidase activity of 650 liquores cerebrospinalis was obtained by means of the substrate Gly-Pro-NHNp (Gly-Pro-4-nitroanilid) at pHs of 5.5 and 7.4. In comparison with a reference collective, the suitability of the method as a supplementary liquor parameter in neurological psychiatric diagnosis was examined. The introduction of the measurement at pH 7.4 can be particularly recommended for the distinguishing of bacterial and nonbacterial meningitis. PMID- 2878448 TI - Interaction, functional relations and evolution of large and small subunits in Rubisco from prokaryota and eukaryota. AB - In early biological evolution anoxygenic photosynthetic bacteria may have been established through the acquisition of ribulose bisphosphate carboxylase oxygenase (Rubisco). The establishment of cyanobacteria may have followed and led to the production of atmospheric oxygen. It has been postulated that a unicellular cyanobacterium evolved to cyanelles which were evolutionary precursors of chloroplasts of both green and non-green algae. The latter probably diverged from ancestors of green algae as evidenced by the occurrence of large (L) and small (S) subunit genes for Rubisco in the chloroplast genome of the chromophytic algae Olisthodiscus luteus. In contrast, the gene for the S subunit was integrated into the nucleus in the evolution of green algae and higher plants. The evolutionary advantages of this integration are uncertain because the function of S subunits is unknown. Recently, two forms of Rubisco (L8 and L8S8) of almost equivalent carboxylase and oxygenase activity have been isolated from the photosynthetic bacterium Chromatium vinosum. This observation perpetuates the enigma of S subunit function. Current breakthroughs are imminent, however, in our understanding of the function of catalytic L subunits because of the application of deoxyoligonucleotide-directed mutagenesis. Especially interesting mutated Rubisco molecules may have either enhanced carboxylase activity or higher carboxylase:oxygenase ratios. Tests of expression, however, must await the insertion of modified genes into the nucleus and chloroplasts. Methodology to accomplish chloroplast transformation is as yet unavailable. Recently, we have obtained the first transformation of cyanobacteria by a colE1 plasmid. We regard this transformation as an appropriate model for chloroplast transformation. PMID- 2878450 TI - The effects of long-term isolation on physiology and behavior in male guinea pigs. AB - Studied were isolation induced effects in guinea pigs. Males (CM) living in two colonies (12 males, 12 females, each) were compared to males (IM) born in the colonies and kept isolated from their 2nd month of age. The findings were: At 19 months of age CM showed higher testosterone and cortisol titers, higher adrenal tyrosine hydroxylase activities and higher seminal vesicles weights than IM. Body, spleen, and adrenal weights did not differ. Thus gonadal, adrenomedullary, and adrenocortical activities appear higher in CM. Adrenal functioning indicates that isolation per se is no more stressful than group living. At their 13th month of age CM and IM did not differ in their behaviors during a 1 hr open-field exposure. This is not considered to result from similar 'emotional temperaments' but rather from an inappropriate procedure to study 'emotionality' in adult guinea pigs. At their 14th month of age CM and IM were placed into the home cage of a male experienced fighter for 15 min. The agonistic encounters between the resident and CM occurred more frequently and were more escalated than between the resident and IM. IM may be a weaker stimulus for attack possibly due to a decreased production of androgen dependent pheromones as indicated by the decreased seminal vesicles weights. Eight IM placed into the colonies at their 16th month of age lost 16.3 to 20.9% of their initial body weights. Three IM died within 8 days although they were not attacked by CM. The 5 surviving males gained low ranking social positions, showed a high degree of arousal and probably were not able to reproduce.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878452 TI - [Changes in the health state of schizophrenic patients in neuroleptic therapy]. AB - The state of health of 135 schizophrenic patients was examined during therapy with a nigrostriatal (Haloperidol) and a mesolimbic (Clozapin) neuroplegic drug, and compared with the situation during treatment without neuroplegics. Among the methods used was the state of health scale of von Zerssen; the neuroleptic threshold was tested using Haase's handwriting test. There was evidence that the patient's health was primarily affected, but individual differential treatment with neuroplegics produced a significant improvement in this important respect. Contrary to Haase, we noticed nothing to convince us of a link between the antipsychotic efficacy of the neuroplegics under investigation and the neuroleptic threshold. PMID- 2878454 TI - [Clinical aspects of benzodiazepines]. AB - The wide therapeutic spectrum of benzodiazepines is well known. This is due to its neuropharmacological, e.g. anxiolytic, sedative-hypnotic, muscle relaxing and anticonvulsant effects. The existence of an antidepressive effect could not be proven up till now. The anxiolytic and the hypnotic effects are considered as the most important events. But it has to be pointed out that the pharmacotherapy of anxiety is only one of the therapeutic approaches towards the problem. A way how to deal with anxiety and other problems could be well discussed and supported in Balint-groups, which are widely offered especially for those, who have not been trained in psychotherapy. Unfortunately a misuse of benzodiazepines is still widely existing. Especially after longer treatment the patients often become addicted to the drugs. Therefore we suggest a thorough consideration of these side effects before any long term treatment with benzodiazepines is decided. PMID- 2878453 TI - ["Soteria Bern." Initial experiences with a new milieu therapy for acutely schizophrenic patients]. AB - The authors report first clinical experiences with 28 schizophrenic patients who were treated and socially rehabilitated by a specially selected team in a small, stimulus-protected, continuous, open and community-near environment (therapeutic community "Soteria Bern"). The therapeutic concept is based on the vulnerability- and information-processing hypothesis and on further psycho-, socio- and milieutherapeutic experiences with schizophrenics. Neuroleptic drugs were used in comparatively very small doses. With about 2/3 positive outcomes, the first results are encouraging. In a research project over several years they will be systematically compared with more traditional treatment strategies. PMID- 2878455 TI - Factors affecting TRH test results. PMID- 2878457 TI - The acute effects of ethanol on auditory event-related potentials. AB - The acute effects of ethanol on the ERPs evoked by auditory stimuli were investigated using 0 g/kg, 0.3 g/kg and 0.54 g/kg ethanol dose. Ethanol was administered to 13 subjects single blind and orally in 20% v/v orange juice. Each subject received one of the three doses at three separate testing sessions. The ERPs were monitored at Cz in the 10-20 system in an odd ball paradigm. At the 0.54 g/kg ethanol level, an increase in latency was observed in the N1, P2, N2 components under both stimuli type conditions. The latency and amplitude of the P3 component were affected by ethanol at both dose levels. The amplitude of P3 was reduced and the latency increased in a dose-dependent manner. These characteristics of the P3 were observed under the target stimuli condition. The findings of the study suggested that stimulus attention, as reflected by N1 amplitude, was affected at the moderate ethanol dose level while stimulus categorisation, as reflected by P3 latency, was affected at the low ethanol dose level, with increased effects at the moderate dose level. PMID- 2878456 TI - Does the excitatory amino acid receptor antagonist 2-APH exhibit anxiolytic activity? AB - The activity of 2-amino-7-phosphonoheptanoic acid (2-APH), an antagonist of the NMDA subtype of glutamate receptor, was tested in several animal models of anxiolytic activity in rats and mice and compared with the activity of the standard benzodiazepine anxiolytic, diazepam. 2-APH was effective, but about 100 times less potent than diazepam in antagonising the suppressive effects of punishment on locomotor activity in the four-plate test in mice. 2-APH was also effective in enhancing exploration of the open, exposed arms of a plus maze, without altering exploration of the enclosed arms. Again 2-APH was about 100 times less effective than diazepam. In contrast to diazepam, 2-APH was ineffective in antagonising the pro-punishment properties of the anxiogenic beta carboline DMCM in a modified four-plate test, and in antagonising the discriminative stimulus provided by pentylenetetrazol. These results are discussed in the context of the equivalence of the antagonism of excitatory mechanisms and the enhancement of inhibitory systems as anxiolytic treatments. PMID- 2878458 TI - Effects of centrally administered H2 antagonists in the behavioral despair test. AB - Injection of the histamine-2 (H2) receptor antagonist cimetidine into the lateral ventricles of mice produced a dose-related reduction in swimming in the behavioral despair test. This response can be attenuated by intracerebroventricular (ICV) injection of the histamine-1 (H1) receptor antagonist chlorpheniramine, or the H2 receptor agonist impromidine, given simultaneously with cimetidine. At doses which blocked cimetidine, neither chlorpheniramine nor impromidine alone had effects on swimming. A similar decrease in swimming behavior was also seen after ICV injections of the non imidazole H2 antagonist, BMY 25,368. This effect of BMY 25,368 was also attenuated by chlorpheniramine and impromidine. These results suggest that H1 and H2 receptors in the brain may mediate opposing behavioral effects. PMID- 2878459 TI - Reversal by alpha-2 agonists of diazepam withdrawal hyperactivity in rats. AB - Rats were made diazepam dependent by chronic treatment with daily injections of the drug, 20 mg/kg, IP, for 3 weeks. On abrupt termination of the drug, the animals showed withdrawal hyperactivity which was indicated by increased horizontal locomotion and vertical activity, and diarrhoea. The peak effect was seen 3 days after the withdrawal of diazepam. Effects of various alpha 2 agonists, clonidine, guanfacine and B-HT 920, were studied on the diazepam withdrawal phenomena. Clonidine (100 micrograms/kg, IP) given twice a day at an interval of 12 h prevented both withdrawal-induced hyperactivity and diarrhoea. On the contrary, equimolar doses of guanfacine and B-HT 920 failed to reverse withdrawal-induced hyperactivity but attenuated the effect of diarrhoea. However, higher doses (500 micrograms/kg, IP) of guanfacine and B-HT 920 given twice a day at 12-h intervals were found to be effective. Pretreatment with yohimbine (1.5 mg/kg, IP) reversed the protective effect of clonidine, indicating the involvement of alpha 2 receptors in the action of clonidine. PMID- 2878460 TI - Effects of zolpidem, a new imidazopyridine hypnotic, on the acquisition of conditioned fear in mice. Comparison with triazolam and CL 218,872. AB - Benzodiazepines and other compounds which act at benzodiazepine binding sites have been shown previously to attenuate the acquisition of conditioned fear in rodents when administered before the acquisition session, an effect which may parallel the disruption of human memory produced by anxiolytics and sedatives. Such an action is usually, but not invariably, produced by doses which have direct behavioural depressant effects. The present study was carried out to extend previous work by investigating the effects of the hypnotic benzodiazepine triazolam and the nonbenzodiazepines zolpidem and CL 218,872 on the acquisition of learned fear in mice. All these drugs reduced locomotor activity shortly after injection. They also produced disruptions of the acquisition of learned fear. Triazolam exerted behavioural effects similar to those found previously with other benzodiazepines, the does which disrupted the acquisition of conditioned fear being similar to, or lower than, the doses which depressed locomotion. In contrast, the results indicated that zolpidem was more potent at reducing locomotion than at interfering with fear conditioning, a result which may reflect the preferential sedative action of zolpidem. PMID- 2878461 TI - Changes in noradrenaline plasma levels and behavioural responses induced by benzodiazepine agonists with the benzodiazepine antagonist Ro 15-1788. AB - Noradrenaline (NA) plasma levels were examined in 18 healthy volunteers on 2 consecutive days after a single treatment with either lormetazepam (0.06 mg/kg) (LMZ group), flunitrazepam (0.03 mg/kg) (FNZ group) or placebo (PLA group) in combination with the benzodiazepine (BZ) antagonist Ro 15-1788 (0.1 mg/kg). Behavioural responses (mood changes, anxiety) were also investigated in parallel. Both BZ decreased NA plasma levels to 50% of the basal values 10 min after the injection; administration of Ro 15-1788 15 min later reinstated NA plasma levels to basal values. A second administration of Ro 15-1788 (0.1 mg/kg) 24 h after BZ or PLA treatment increased NA plasma levels, estimated 10 min after the injection in both the LMZ- and the FNZ groups, but not in the PLA group. Behavioural responses measured under the same treatment also indicated minor anxiety responses followed by mood impairment. These data suggest that a stressful situation may be precipitated by the antagonist Ro 15-1788 24 h after a single BZ treatment, which resembles a withdrawal response, and increases NA plasma levels. PMID- 2878462 TI - Serum concentrations and clinical effect of zuclopenthixol in acutely disturbed, psychotic patients treated with zuclopenthixol acetate in Viscoleo. AB - Zuclopenthixol acetate, 5%, in Viscoleo was administered IM to 19 acutely disturbed, psychotic patients in doses of 50-150 mg. Fifteen patients received one injection, whereas four of the patients had two or three injections, usually with intervals of 3 days. The zuclopenthixol concentrations in serum were measured in series of samples taken from each patient during a 3-day period following the injection. In patients given identical doses serum concentrations of about the same order were obtained. Significant and good correlations were found between dose and maximal serum concentration and between dose and area under the serum concentration curve. The average serum concentration curve obtained when adjusting the data to a 100 mg dose has a maximum of 41 ng/ml after about 36 h, decreasing to 15 ng/ml after 72 h. A dose of 50-150 mg zuclopenthixol acetate in Viscoleo appeared to be sufficient for controlling the symptoms for most acutely disturbed, psychotic patients. The frequency of side effects, including extrapyramidal reactions, was low and the adverse reactions mostly mild, indicating that the risks for severe complications generally might be minimal. With a rapid onset of action, few and mild side effects, good tolerability at the injection site, and a duration of effect of 2-3 days, zuclopenthixol acetate in Viscoleo appears to offer advantages compared to conventional neuroleptic treatment in patients in whom an acute, calming effect is desired. PMID- 2878463 TI - Zuclopenthixol levels in serum and breast milk. AB - Breast milk and serum samples were obtained from six psychotic patients 3 days-10 months after delivery. Five of the women were given zuclopenthixol PO daily, and one was given zuclopenthixol decanoate IM every 2 weeks. Zuclopenthixol was estimated in breast milk and serum by high performance liquid chromatography. The zuclopenthixol levels in milk were found to be 29% of the serum levels on average. Based on the drug levels found in milk, the daily dose to a suckling infant was estimated to be 0.5-5 micrograms zuclopenthixol, corresponding to a dose of 0.01-0.1 mg to an adult. It is not likely that such a low dose would cause any effects or side effects in the infant unless infants are very different from adults concerning metabolism or sensitivity to the drug. The suckling infants included in this study were apparently not influenced by the intake of zuclopenthixol with the milk. PMID- 2878464 TI - Hypotension-induced hypokalaemia in sheep. AB - Plasma K+ was measured in Merino ewes during 50-90 min periods of hypotension induced by sodium nitroprusside, isoprenaline, verapamil or nifedipine. Doses were adjusted to produce falls in systemic blood pressure of approximately 20 mmHg. All of these drugs caused decreases in plasma K+ which could not be attributed to increased urinary excretion of K+. In all cases plasma renin activity increased during the hypotension. Plasma aldosterone concentration which was measured in some sodium nitroprusside experiments also increased during the hypotension. However, enhancement of the plasma renin activity and plasma aldosterone concentration responses by prior sodium depletion of the sheep by furosemide administration or suppression of the plasma renin activity and plasma aldosterone concentration responses by prior salt loading did not influence the magnitude of the hypotension-induced hypokalaemia. PMID- 2878465 TI - Psychiatric disorders: neurotransmitters and neuropeptides. PMID- 2878466 TI - Neurons with multiple messengers--distribution and possible functional significance. PMID- 2878468 TI - Animal models in psychiatric research. PMID- 2878467 TI - Synthesis, function, and degradation of catecholamine neurotransmitters. PMID- 2878469 TI - Cholinergic dysfunction in Alzheimer disease: cause or effect? PMID- 2878470 TI - Responses of neurons in isolated preparations of the mammalian central nervous system. PMID- 2878472 TI - [Value of serum gamma-glutamyltransferase in the diagnosis of alcoholism]. PMID- 2878471 TI - [Financial cost of the treatment of peptic ulcer]. PMID- 2878474 TI - [Use of the internal mammary artery as a free aortocoronary graft]. PMID- 2878475 TI - [Bilateral temporomandibular dislocation. Drug induced?]. PMID- 2878476 TI - [Takayasu's disease in Italy. Impact and clinico-diagnostic aspects]. PMID- 2878473 TI - [Serum activity of gamma-glutamyltranspeptidase, adult and fetal forms in patients with compensated and decompensated forms of alcoholic cirrhosis]. PMID- 2878477 TI - Central effects of N-allyl,N'-methyl-barbital and N-allylmethyprylon in mice. AB - Pharmacological activities (hypnotic, anticonvulsant and convulsant activities, acute toxicity and pentobarbital (PB) synergism) of N-allyl,N'-methyl derivatives of barbiturates and related N-allyl substituted compounds were studied in mice. N Allylhexobarbital (AHB), N-allylglutethimide (AGI) and N-allylmethyprylon (AMP) showed hypnotic activity. N-Allyl,N'-methyl derivatives of barbital (B), phenobarbital (PheB) and PB (AMB, AMPheB and AMPB), AHB and AMP exhibited anticonvulsant activity against pentylenetetrazol (PTZ)-induced seizures. AMP was the most potent agent among the allyl compounds tested in the protective effect against PTZ-induced seizures. N-Allyl, N'-methylallobarbital (AMAlloB) showed a weak convulsant activity at a dose of 640 mg/kg, i.p. All allyl compounds tested showed potentiation of the PB-induced sleep. AMB prolonged the PB-induced sleep 30-fold as compared with the control. These results indicate that AMB, AMP and the other N-allyl compounds possess some depressant effects on the central nervous system. PMID- 2878478 TI - Some central effects of indenolol in experimental animals. AB - Indenolol, a relatively new beta-adrenergic blocking drug, was tested for its effect on the central nervous system. The parameters included its effects on spontaneous motor activity, conditioned avoidance response (CAR) acquisition, pentobarbitone hypnosis, amphetamine induced motor excitation, analgesic activity and rectal temperature in experimental animals. Indenolol was found to significantly decrease the spontaneous motor activity in mice and CAR acquisition in rats. It potentiated the pentobarbitone induced hypnosis and antagonized amphetamine induced excitatory behaviour in mice. It did not show a marked analgesic effect of its own but potentiated the analgesia induced by the subanalgesic dose of morphine. It also produced a significant hypothermic effect in mice. All the effects except on CAR acquisition were obtained in the dose of 50-75 mg/kg body weight administered intraperitoneally. It enhanced CAR acquisition in the specific dose of 5 mg/kg. These observations indicate that indenolol possesses an anxiolytic effect similar to that reported for propranolol and some other beta-blocking drugs. PMID- 2878479 TI - [Acute aortic regurgitation due to Takayasu arteritis]. PMID- 2878480 TI - Ventilatory responses of the rat to mild hypercapnic stimulation before and after almitrine bismesylate. AB - In pentobarbital-anesthetized rats, hyperventilatory responses to rectangular mild hypercapnic normoxic gas mixtures inhalation were analysed. Hyperventilation dynamics were characterized by a logarithmic curve whose delay (T0) and half response time (T50-T0) were calculated. These values were established in nervously intact (IR), vagotomized (XT), surgically chemodenervated (CDN) rats and in IR-rats after almitrine bismesylate (ALM) pretreatment. In IR and XT-rats, T0 and T50 - T0 were larger after 0.5 and 1.0% CO2 step-changes than after 1.5% CO2 step-change (10 sec vs 2 sec for T0). In CDN rats, this 1.5% CO2 hyperventilation was delayed, but this delay was shorter (5 sec) than in IR or XT rats inhalating 0.5 and 1.0% CO2. After ALM pretreatment, the amplitude of the ventilatory response to a same rise in PETCO2 was increased. T0 and T50 - T0 during 0.5 and 1.0% CO2 step-changes became identical to the time values obtained with the 1.5% CO2 mixture in untreated rats. Variations in amplitude and dynamics of the ventilatory responses to CO2 provoked by ALM pretreatment may be explained by an increased sensitivity of the peripheral chemoreceptors to CO2, T0 at the time of the weakest stimuli becoming equal to that observed for a higher hypercapnia and no longer different from the lung to carotid bodies circulation time. So, the delayed and smoothed responses to 0.5 and 1.0% CO2 in IR and XT rats were attributed to a PaCO2 too weak to stimulate the peripheral chemoreceptors. The latency and half response time were higher than in CDN rats due to a weaker induced difference in PETCO2. Hyperventilation dynamics changes induced by ALM allowed to differentiate between peripheral and central chemoreception in ventilatory control. PMID- 2878481 TI - [Autotransplant of a testicle: report of a case and review of the literature]. PMID- 2878482 TI - [Asthma therapy today]. PMID- 2878483 TI - [A new generation of H1-receptor antagonist antihistaminics]. PMID- 2878484 TI - Salmonella subdural empyema in a patient with brain metastasis. PMID- 2878485 TI - [Buli from Shariakandi (1)]. PMID- 2878486 TI - Localized polyarteritis nodosa: cases involving the lower extremities and the breast. AB - Two patients with cutaneous polyarteritis nodosa with nodules in the lower extremities and another patient with an unusual presentation of polyarteritis nodosa involving only the arteries of the breast are reported. PMID- 2878487 TI - Macrophage spreading inhibition test as an alternate method for in vitro assessment of cell-mediated immunity against Entamoeba histolytica. AB - During cellular immune responses sensitized lymphocytes release a number of mediators collectively known as 'lymphokines'. The assaying of macrophage spreading inhibition (MSI) factor released by sensitized lymphocytes was employed as an alternative procedure for in vitro detection of cell-mediated immunity (CMI) in animals immunized with amoeba antigen preparation. The MSI test was compared with macrophage migration inhibition test. A well defined CMI was detectable in animals immunized by amoebic antigen in combination with Freund's complete adjuvant (FCA). Macrophage spreading was found greatly inhibited when peritoneal exudate cells from these animals were cultured in the presence of specific antigen. The optimal time for the development of typical reaction was 30 min. Incubation for a longer time resulted in macrophage clumping. PMID- 2878488 TI - Evaluation of sinefungin for the treatment of Trypanosoma (Nannomonas) congolense infections in goats. AB - Caprine Trypanosoma (N.) congolense infections were treated with sinefungin, an antifungal antibiotic nucleoside. Single doses from 10 to 20 mg/kg bodyweight given intramuscularly were not curative for goats; single doses of 25 and 50 mg/kg were toxic, and caused death. Five and 7.5 mg/kg administered twice daily over a three-day period, resulted in a cure in 2 animals, while 2 others relapsed. All animals relapsed when given a single daily dose of 5 or 7.5 mg/kg for 4 consecutive days. When such doses were given twice a day, they caused death in 50% of the goats and the remainder were cured. Raised serum urea levels indicated the severe nephrotoxic side-effects of sinefungin even at subcurative levels. Histopathological examinations revealed an acute tubulonephrosis. PMID- 2878489 TI - [Beta agonists in the treatment of cardiac insufficiency]. PMID- 2878491 TI - Stem cell autografting for chronic granulocytic leukemia. PMID- 2878490 TI - Plasma somatostatin and plasma glucagon in long-term IDDM without residual B-cell function. No effect of different long-term metabolic control. AB - To further study the elevated plasma somatostatin (SRIF)--and reduced plasma glucagon concentrations found in IDDM patients without residual B-cell function compared to normal controls, we investigated 39 such patients, randomly assigned to three different insulin treatment regimens; conventional therapy with two injections a day (CTh), insulin pump (CSII) and multiple injections (MI), for 1 year. They were given an arginine infusion (0.5 g/kg/20 min). The mean basal plasma SRIF values in the CTh, CSII and MI groups were 20.8 +/- 3.3, 18.6 +/- 1.8 and 20.6 +/- 2.8 pmol/l and the mean basal plasma glucagon values were 30 +/- 5.7, 19 +/- 2.3 and 27 +/- 4.7 pmol/l, respectively. Both SRIF and glucagon increased in all groups in relation to arginine infusion. For both hormones, the mean values were highest in the CTh group, lowest in the CSII group, although the differences were not significant. The mean HbA1 values for the last 3 months within the test were 10.0 +/- 0.5, 8.8 +/- 0.3 and 9.1 +/- 0.5%, respectively, in the same order as above. The CTh group had significantly higher HbA1 values than the CSII group (p less than 0.02). We conclude that small differences in long term blood glucose control are of inconsiderable importance for the islet hormonal response to arginine found in IDDM without B-cell function. PMID- 2878492 TI - [Hypertension management in practice, 1986]. AB - Persons with persisting (at least 3 measurements over several weeks) borderline blood pressure elevation or established hypertension should always be instructed to follow general non-pharmacological measures. Antihypertensive pharmacotherapy is recommended in the following situations: in hypertensive emergencies, immediately; if the hypertension is not due to a surgically remediable cause, in patients with documented (at least 3 measurements) blood pressure elevation to diastolic values greater than 100 mm Hg; in patients with "mild" hypertension (diastolic up to 104 mm Hg) which does not decrease to less than 160/95 mm Hg following 3 to 6 months of treatment with general non-pharmacological measures; in persons with borderline blood pressure values (141-159/91-94 mm Hg) that persist following 6 to 12 months of general measures and only if they have severe additional cardiovascular risk factors; in patients with pronounced isolated systolic hypertension (greater than 180 mm Hg). In elderly patients who are frail or have evidence of advanced cardiovascular disease, dementia or other debilitating illnesses, blood pressure-lowering drugs should generally be reserved for diastolic blood pressure values consistently exceeding 110 mm Hg. There have recently been important new developments in antihypertensive pharmacotherapy. Two new pharmacological principles, the calcium entry blockers and angiotensin converting enzyme (ACE) inhibitors, have been introduced widely into practical hypertension treatment. On the other hand, concern has arisen that the conventional, thiazide-diuretic based therapy, despite its established beneficial influence on blood pressure and most cardiovascular complications, may not significantly improve or may sometimes even adversely affect coronary prognosis because of metabolic side effects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2878493 TI - [Advances in neurology]. PMID- 2878494 TI - NIMH review of fraud charge moves slowly. PMID- 2878496 TI - Neuroleptic malignant syndrome: three episodes with different drugs. AB - This is an illustrative case of a patient with neuroleptic malignant syndrome whom we believe is the first described in the world's literature to have this syndrome on three occasions, each time after having received a different neuroleptic agent. PMID- 2878495 TI - Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. AB - In postmortem studies of patients with schizophrenia, D2 dopamine receptors in the basal ganglia have been observed to be more numerous than in patients with no history of neurological or psychiatric disease. Because most patients with schizophrenia are treated with neuroleptic drugs that block D2 dopamine receptors in the caudate nucleus, it has been suggested that this increase in the number of receptors is a result of adaptation to these drugs rather than a biochemical abnormality intrinsic to schizophrenia. With positron emission tomography (PET), the D2 dopamine receptor density in the caudate nucleus of living human beings was measured in normal volunteers and in two groups of patients with schizophrenia--one group that had never been treated with neuroleptics and another group that had been treated with these drugs. D2 dopamine receptor densities in the caudate nucleus were higher in both groups of patients than in the normal volunteers. Thus, schizophrenia itself is associated with an increase in brain D2 dopamine receptor density. PMID- 2878497 TI - The association of neurofibromatosis, pheochromocytoma, and somatostatin-rich duodenal carcinoid tumor. AB - The association of neurofibromatosis and pheochromocytoma is well recognized; more recently, attention has been drawn to links between neurofibromatosis, pheochromocytoma, and ampullary somatostatin-rich carcinoid. Because of this association, the duodenum was explored during a recent laparotomy for resection of bilateral pheochromocytoma in a patient with von Recklinghausen's disease. A clinically unsuspected ampullary tumor was discovered; this proved to be in part a ganglioneuroma and in part a somatostatin-rich carcinoid. This paper presents full details of this carefully investigated and documented case and reviews the recent advances in this field. These studies lead us to conclude that: the clinical association of neurofibromatosis, pheochromocytoma, and D cell carcinoids ("somatostatinomas") of the ampullary region is confirmed; this association may be more common than has been previously thought, and the duodenum should be carefully examined in any patient with neurofibromatosis who undergoes laparotomy for pheochromocytoma. PMID- 2878498 TI - Evidence for nongastrin-mediated somatostatin inhibition of parietal cell function. AB - Somatostatin (SRIF), a tetradecapeptide, has been reported to suppress gastrin release and hence inhibit acid secretion in vivo. This study was performed to determine whether SRIF has any direct effect on parietal cell (PC). Isolated gastric cells were prepared by collagenase digestion and calcium chelation of rabbit fundic mucosa. PC enrichment (75% +/- 5%) was accomplished by velocity sedimentation with an elutriator rotor. Acid, as assessed by the accumulation of 14C-aminopyrine (AP) and macromolecular (intrinsic factor [IF]) secretion were used as markers of PC function. Cells were stimulated with histamine (H) (10(-6) mol/L). SRIF (10(-10) to 10(-6) mol/L) significantly inhibited H-stimulated 14C AP accumulation (p less than 0.05). Inhibition of H-stimulated IF release was less sensitive, occurring at 10(-8) and 10(-7) mol/L (p less than 0.05), and loss of inhibition was observed at 10(-6) mol/L (p less than 0.05). These results demonstrate a direct inhibitory action of SRIF on PC secretion. The difference in inhibitory effect on IF and proton secretion is consistent with the postulation that SRIF may function at more than one site within the PC. PMID- 2878499 TI - Management of the Zollinger-Ellison syndrome in patients with multiple endocrine neoplasia type I. AB - Treatment of the Zollinger-Ellison syndrome (ZES) in patients with multiple endocrine neoplasia type I (MEN I) is controversial. Unlike other patients with ZES who have a single tumor and in whom curative surgical resection is possible and desirable, patients with ZES and MEN I tend to have multiple pancreatic islet cell tumors. Therefore the chances for surgical cure are usually different. A retrospective review of 25 patients with ZES as a manifestation of MEN I seen at our institution between 1960 and 1984, an interval during which histamine type 2 (H2) receptor antagonists were introduced, provided an opportunity to study this problem. Follow-up averaged 6 1/2 years. All patients diagnosed before 1979 (14 patients) underwent surgical exploration. Ten patients (71%) had pancreatic procedures (five enucleation, four partial pancreatectomy, and one enucleation of multiple nodules with subsequent total pancreatectomy). None of these procedures was curative, and all patients required further medical and/or surgical therapy for peptic ulceration. Eighteen patients (72%) underwent gastric surgery. Seven patients had subtotal gastrectomy, five of whom required subsequent total gastrectomy. Thirteen patients ultimately had total gastrectomy. There were no immediate postoperative deaths. All patients with diagnoses since 1979 (11 patients) had H2-antagonist therapy as primary treatment. No significant complications were associated with this approach during a mean treatment period of 26 months. Only one of these patients subsequently has required gastric surgery. The proved efficacy of H2 antagonists, coupled with the recognition of the diffuse nature of the pancreatic disease in these patients, has led to a change in the therapeutic approach over the period reviewed. H2-antagonist therapy should be the initial treatment of choice in patients with MEN I who have ZES. PMID- 2878500 TI - Use of a somatostatin analog (SMS 201-995) in the glucagonoma syndrome. AB - A long-acting somatostatin analog, SMS 201-995, is now available to treat the hormonal manifestations of islet cell tumors. We report its use in a patient with a metastatic glucagonoma refractory to conventional therapy. This patient, who was severely disabled by the rash of necrolytic migratory erythema and brittle diabetes mellitus, allowed us to evaluate the therapeutic efficacy of SMS 201-995 and to gain insight into the origin of the rash. SMS 201-995 was administered subcutaneously (.05 mg twice a day). The rash improved markedly within 48 hours and was completely resolved within 1 week of treatment. Insulin requirements decreased from 90 U/day to zero during the first week of treatment. Corresponding to improvement in clinical symptoms circulating glucagon levels showed a marked decrease. There was no substantial change in plasma or urinary levels of zinc or in plasma amino acid levels. When SMS 201-995 was stopped, the rash recurred within 36 hours and it improved within 48 hours of readministration. The rash and diabetes have remained well controlled during 8 months of therapy but no change in tumor size has been seen on CT scan. The rapid changes in the rash related to the administration of SMS 201-995 indicate that the pathogenesis of necrolytic migratory erythema is probably due to circulating hyperglucagonemia or some other hormonal substance produced by the tumor. PMID- 2878501 TI - Heavy metal inhibition of carnitine acetyltransferase activity in human placental syncytiotrophoblast: possible site of action of HgCl2, CH3HgCl, and CdCl2. AB - The effect of the heavy metal toxicants HgCl2, CH3HgCl, and CdCl2 on the acetylating activity of membranous carnitine acetyltransferase (CarAc) in membrane vesicles from the maternal surface of human placental syncytiotrophoblast has been investigated. CarAc was inhibited by inorganic and organic mercury and cadmium. Carnitine acetylation was inhibited by as little as 5 microM mercury, with complete inhibition at 50 microM inorganic and organic mercury. Inhibition by cadmium was incomplete (less than 60%) at 500 microM CdCl2. Kinetic studies using Hanes plots revealed a mixed type of inhibition of CarAc by the metals. Cysteine preincubation decreased the amount of inhibition of CarAc by the metals. These results indicate that the inhibition of CarAc by heavy metals occurs by binding of the sulfhydryl on the enzyme by the metals. This interaction may be a mechanism of the heavy metal-induced fetotoxicity. PMID- 2878502 TI - Validation of an in vivo developmental toxicity screen in the mouse. AB - A test system for identifying toxicity, including potential teratogenicity has been developed that is based on growth and viability of embryonic, fetal, and postnatal mice (J Toxicol Environ Health 10:541-550, 1982). To test the utility of this assay, a series of 55 compounds was administered to timed-pregnant ICR/SIM mice during organogenesis. The test compounds included known teratogens, known nonteratogens, and equivocal teratogens. They represented a wide variety of classes including pesticides, organic solvents, metals, steroids, nutrients, food additives, antimetabolites, alkylating agents, and pharmaceutical agents. A single dose level, at or near the level producing overt maternal toxicity in preliminary range-finding studies, was administered by gavage on gestation days 8 through 12. Females were allowed to deliver; litter size and weight on the day of birth and 2 days postpartum were recorded, and stillborns were examined. Dams that had not given birth by gestation days 21 or 22 were killed and their uteri were examined. The results confirmed a strong correlation between reported teratogenic activity and embryo/fetal viability, and/or postnatal growth and viability. The results indicate that this test system is an effective, cost efficient means of prioritizing compounds for more detailed teratogenicity testing. PMID- 2878504 TI - Karyotype, growth, and cell cycle analysis of human embryonic palatal mesenchymal cells: relevance to the use of these cells in an in vitro teratogenicity screening assay. AB - Human embryonic palatal mesenchyme (HEPM) is an established cell line that is presently under investigation as an in vitro prescreening assay used to determine the teratogenic potential of chemicals. We describe here general growth characteristics, karyotype, and cell cycle analysis of these cells. HEPM cells had plating efficiencies of less than 95% and displayed notable contact growth inhibition following an exponential growth phase that lasted for approximately 6 days. These cells had the diploid karyotype of a female human embryo. The chromosomal complement showed no dramatic change between passage 5 and 14. Flow cytofluorometry analysis using bromodeoxyuridine (BrdU) pulse labeling and a direct immunofluorescence anti-BrdU FITC probe revealed that the total cell cycle transit time was approximately 22 hr: the duration of G1 was 12.2 hr, S was 6.1 hr, and G2-M lasted for 3.7 hr. The results indicate that HEPM cells met the criteria regarding karyotype stability that were assumed by the National Toxicology Program of the USA. PMID- 2878503 TI - Teratogenic effects of the fungicide dinocap in the mouse. AB - The teratogenic potential of the fungicide dinocap was evaluated in CD-1 mice. Pregnant mice were dosed by intubation with dinocap in corn oil on gestation days 7-16. Doses used were 0, 5, 10, 20, 40, 80, and 120 mg/kg/day, based on day 6 weight. Dams were killed on day 18, at which time fetuses were counted, weighed, and preserved for necropsy or skeletal examination. The highest dose killed 80% of the dams dosed, while 29% of the dams in the 80 mg/kg group died during dosing. There was no dose-related maternal mortality at lower doses. Net maternal weight gain was affected only at 80 mg/kg/day. There were no live fetuses at 120 mg/kg/day. The number of live fetuses per litter was decreased and resorptions increased at 80 mg/kg. Dose-related decreases in gravid uterus weight and fetal weight were significant at all doses of dinocap. Cleft palate was found in fetuses at 5(1/234; 0.4%), 20(46/195; 23.6%), 40(140/185; 75.5%), and 80(63/85; 74.1%) mg/kg/day. There was a dose-related increase in supernumerary ribs and a low frequency of exencephaly and umbilical hernia at high doses. This study shows that dinocap is teratogenic in the CD-1 mouse at doses well below those causing maternal toxicity. PMID- 2878505 TI - Failure of epoxide formation to influence carbamazepine-induced teratogenesis in a mouse model. AB - The teratogenic potential of the anticonvulsant drug carbamazepine was determined following chronic oral administration in two inbred mouse strains (SWR/J and LM/Bc). The drug was administered in the animal's diet in concentrations equivalent to 0, 1,000, 1,500, or 2,000 mg/kg body weight, with treatment starting 2 wks prior to mating and continuing throughout gestation. Fetal examination failed to reveal a significant pattern of malformation in either strain at any treatment level. Levels of plasma carbamazepine and its metabolite, carbamazepine-10,11-epoxide, were determined by high pressure liquid chromatography. There was no correlation with either of these compounds and the incidence of fetal abnormality. The inherent teratogenicity of carbamazepine is significantly lower than that of other anticonvulsant drugs that have been similarly tested in an animal model. PMID- 2878506 TI - Studies on the embryopathic effects of ethanolamine in Long-Evans rats: preferential embryopathy in pups contiguous with male siblings in utero. AB - The embryopathic effects of high doses of ethanolamine were evaluated in pregnant Long-Evans rats during the "critical period" or organogenesis. Ethanolamine was given by gavage at levels of 0, 500, 300, or 50 mg/kg/day (24%, 14.4%, or 2.4% of the LD50 value). Ethanolamine caused dose-dependent increases in intrauterine deaths, malformations, and intrauterine growth retardation. Embryolethality caused by 500 mg/kg of ethanolamine was not random: male pups contiguous to two male siblings (designated mMm) were almost quantitatively replaced by resorptions that were contiguous to two live male pups (designated mRm) (mMm pups constituted 6.7% of control implants and decreased to only 0.9% of group II implants while mRm resorptions increased from 0.3% in controls to 5.6% in group II dams). Intrauterine growth retardation and increases in gross structural anomalies (considered indicative of depressed fetal growth) more severely affected male than female offspring at all dose levels. Pups of either sex who were contiguous to male siblings were more adversely affected than those offspring contiguous to one or more female siblings. As ethanolamine was given prior to the period of greatest fetal growth and fetal sex steroidogenesis, it is suggested that intrauterine levels of female sex steroids (estradiol) enhance fetal repair of cellular damage while testosterone inhibits fetal repair or exacerbates previous embryonic damage by some unknown mechanism. Such interaction furthers the concept that intrauterine position affects the endpoints of developmental toxicity, as expressed at parturition. PMID- 2878507 TI - The induction of supernumerary ribs in rodents: role of the maternal stress. AB - Increased incidences of supernumerary ribs (SNR) are a relatively common finding in standard teratology bioassays, and previous studies have indicated a possible correlation between their occurrence and general maternal stress. The present study describes the effects of immobilization stress on the induction of supernumerary ribs. To isolate the sensitive period of SNR induction, Sprague Dawley rats and CD-1 mice were treated with 300 and 1,500 mg/kg, respectively, of sodium salicylate on single days 7-11 of gestation. In the rat, day 10 was found to be the sensitive period of lumbar rib induction (32% SNR vs 10% on other days) while day 9 was critical in the mouse (71% SNR vs less than 29% on other days). In a second set of experiments, maternal stress was accomplished by restraining two groups of gravid females in the supine position for 12 hours on the predetermined sensitive day. One group was immobilized from 9 am to 9 pm, while the second group was restrained from 9 pm to 9 am. Concurrent controls were food and water deprived for similar periods. Additional untreated controls were also included. An increase in supernumerary ribs was noted in stressed mice but not in rats. The 9 am to 9 pm mouse group exhibited the highest increase in supernumerary ribs (41%) as well as significant incidences of fused ribs and exencephaly. A significant linear relationship between maternal weight loss during treatment and increases in supernumerary ribs was also noted. Results suggest that for some compounds, supernumerary ribs may be the indirect result of agent-induced, generalized maternal stress in the CD-1 mouse. PMID- 2878508 TI - Sirenomelia: analysis in the cadmium- and lead-treated golden hamster. AB - Sirenomelia, a fusion of the lower extremities, is believed to result from a median, bilateral symmetric defect of the caudal portion of the embryo at a very early stage in development. Anomalies of the gastrointestinal and urogenital systems are commonly associated with this malformation. Sirenomelia is not an embryo-lethal condition but typically is incompatible with postnatal life when combined with the associated malformations. In this study, intravenous treatment of hamsters with a combination of cadmium and lead on the morning of the eighth day of gestation resulted in 1.4, 22.2, and 35.6% of the viable fetuses displaying sirenomelia in litters recovered on days 15, 12, and 10 of gestation, respectively. With the exception of several fetuses with exencephaly, most structures cranial to the level of the umbilicus were normal. Caudal abdominal and pelvic structures were severely affected, with agenesis or dysgenesis of the kidneys, bladder, umbilical arteries, and external genitalia frequently noted. The administration of a combination of cadmium and lead has proven to be an effective and consistent means of inducing sirenomelia in the golden hamster. PMID- 2878510 TI - Changes in fibrinolytic capacity and lipoprotein pattern during long-term treatment with warfarin. PMID- 2878509 TI - Glucocorticoid receptor-mediated teratogenesis and cell proliferation in the limbs and face of the chick embryo. AB - The susceptibility of the face region of the chick embryo to the teratogenic action of intraamniotically injected hydrocortisone contrasts with the resistance of the limbs to its action while at the same time their dysmorphogenesis may be induced by other agents. Since glucocorticoid receptors were shown to mediate face teratogenesis, their development was investigated in freshly dissected limb buds of 3-, 3.5-, and 4-day-old chick embryos in comparison with the face region. The specific binding of 3H-dexamethasone to molybdate-stabilized glucocorticoid receptors was estimated by the dextran-coated charcoal method and complemented by cytologic analysis of mitotic activity in control and hydrocortisone-treated embryos. The glucocorticoid receptors were found in both organ anlagen already on day 3 when their concentration in femtomoles per microgram DNA was significantly higher in the face region. Accordingly, on day 3 intraamniotic hydrocortisone inhibited the mitotic activity in the face without affecting the developing limbs. On days 3.5 and 4 the concentration of glucocorticoid receptors was similar in both organ anlagen. Administration of hydrocortisone on day 4 induced mitotic depression in the face as well as in the limbs. However, the degree of inhibition appeared to be dependent upon the actual mitotic rate. In the face region where the mitotic activity culminated at that time, the inhibition was much deeper and longer-lasting than in the developing limbs characterized by continuous decrease of proliferation rate in controls. These findings are consistent with a view that glucocorticoid receptors are a prerequisite, but not the only factor in receptor-mediated teratogenesis. PMID- 2878511 TI - [Alcohol-related admissions to a department of internal medicine. The value of gamma GT as a screening method for heavy alcohol consumption and alcohol-related admissions]. PMID- 2878512 TI - Reduced complexity of RFLP for HLA-DR typing by the use of a DR beta 3' cDNA probe. AB - The polymorphism of the HLA system has been defined by alloantisera, monoclonal antibodies, MLC reactivity, protein chemistry and RFLP patterns in DNA analysis. Typing for the alleles of HLA-DR at the DNA level as an additional typing technique is useful since any nucleated cell can be used. Moreover, it is not known whether the additional polymorphism found at the DNA level in an unambiguous serotype is of functional importance and thus needs to be included in HLA-DR typing. A main problem in DNA typing is the interpretation of the complex patterns in Southern blot analysis, especially in heterozygous individuals. Therefore we constructed subprobes from full length DR beta, DQ alpha and DQ beta cDNA to reduce the number of hybridizing fragments while retaining the discriminating capacity. The clearest differences among DR alleles have been found using the restriction enzyme PvuII and the subprobe containing the 3' untranslated region of the DR beta probe. Although further characterization is necessary to be able to type at the DNA level, the simplified patterns facilitate DNA typing in heterozygous individuals for a number of haplotypes. Interestingly, the number of fragments thus obtained corresponds with the number of genes described for DR1 to DRw8 haplotypes. Based upon the finding of common hybridizing patterns in DR3, DR5 and DRw6 it may be concluded that DR3, DR5 and DRw6 have been evolved from a common ancestor. For the same reason DR4, DR7 and DRw9 may have evolved in an identical way. PMID- 2878513 TI - Toxic cardiomyopathy: the effect of antipsychotic-antidepressant drugs and calcium on myocardial protein degradation and structural integrity. AB - In the nonrecirculating isolated perfused rat heart it has recently been described that basal myocardial protein degradation is suppressed by 30% within 5 min of maximal beta-adrenergic receptor occupancy under 5 X 10(-7) M isoproterenol (Lockwood, 1985, Biochem. J. 231, 299-308). This adrenergic controlled proteolytic process presumably contributes to the well-known normal coordination of myocardial protein mass with functional demand. It is presently reported that elevated intracellular calcium is among the messengers that somehow suppress protein degradation. Acute elevation of extracellular calcium to a maximal concentration of 9.0 mM mimicked the simultaneous effects of isoproterenol on increasing inotropy and decreasing protein degradation, although this concentration was eventually lethal. Conversely, infusion of trifluoperazine (TFP), a calmodulin-blocking antipsychotic drug, caused stimulation of protein degradation above basal levels within 5 min. The stimulation of degradation by 30 60% was transient at 5 X 10(-7) M and returned to the control level in 5-10 min. However, TFP produced massive irreversible release of amino acid peptides and proteins at 10(-5) M within 30 min, followed by grossly observable cell structural disruption and cell separation. The degradative stimulation caused by TFP was potentiated by lowering the normal 2.5-mM extracellular Ca2+ concentration to 1.25 mM. Trifluoperazine at 10(-5) M caused longitudinal separation of myofibrils by disrupting lateral attachments between adjacent Z lines, leading to a loss of lateral myofibrillar registry followed by myofibrillar degeneration. Spot desmosomes were disrupted, leading to lateral cell separation; however, the fascia adherens region of the intercalated disks remained intact and cells maintained end-to-end attachment. Perfusion under the low extracellular Ca2+ concentration of 0.1 mM for 0.5 hr caused separation of the fascia adherens region and spot desmosomes of the intercalated disks as well as disruption of cytoplasmic myofibrils and other changes. Although the structural disorganization caused by perfusion with low (0.1 mM) Ca2+ were similar to those caused by TFP, cells also lost end to end attachment under low Ca2+. Amitriptyline (10(-5) M), thioridazine (10(-5) M), and calmidazolium (10( 6) M) stimulated protein degradation and caused structural damage. It is speculated that the above Ca2+-related phenomena describe the mechanism of the well-known toxic cardiomyopathy resulting from overdoses of some of the antipsychotic-antidepressant drugs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2878514 TI - Immunodiagnosis of Entamoeba histolytica and Ascaris lumbricoides infections in Caucasian and aboriginal Australians. AB - The immunodiagnostic efficiency of an indirect immunofluorescence test (IFAT) and in vitro lymphocyte proliferative responsiveness (cell mediated immunity test, CMIT) used to measure the immunological responses of individuals with known natural Entamoeba histolytica and Ascaris lumbricoides infections, was studied under survey conditions. E. histolytica was common among Aborigines from Cherbourg, Kowanyama and Central Australia, but it was not found in Brisbane Caucasians. The protozoan was selected for the study because it was prevalent and purified antigen was commercially available. Immunodiagnosis for A. lumbricoides was made using an antigen prepared by affinity chromatography. Diagnosis based on frequency distribution of immunological data gave valid assessment of the number of infected individuals in each population studied. PMID- 2878516 TI - [Bilateral seminoma in cryptorchism]. PMID- 2878515 TI - Effect of cyclosporine on islet xenograft survival in the BB/W rat. PMID- 2878517 TI - [Non-clostridial anaerobic infection in complicated cholecystitis]. AB - Results of bacteriological investigations and treatment of 112 patients with complicated forms of acute cholecystitis are described. It was found that in complicated forms of acute cholecystitis an important part was played by associations of bacteria among which neclostridial anaerobes were of leading importance responsible for the aggravation of the inflammatory process and course of the postoperative period. The intracholedochal antibacterial therapy with Dioxidin in combination with antibiotics is thought to be expedient. PMID- 2878518 TI - Keratoconjunctivitis sicca and the treatment of canine colitis. PMID- 2878519 TI - Syrup of ipecac induced emesis: impact of fluids versus no fluids on time until emesis. PMID- 2878520 TI - Papain-induced changes in the guinea pig knee joint with special reference to cartilage healing. AB - The repair of articular cartilage following papain injection into the knee joint of the guinea pig was studied by light and electron microscopy, as well as by autoradiography using tritiated thymidine. Papain injection rapidly produced complete degradation of cartilage proteoglycan. Although a number of chondrocytes were also destroyed, the remaining chondrocytes showed mitotic cell division with resultant formation of cell clusters. Such chondrocytic regeneration, however, did not contribute significantly to the repair of cartilage tissue. On the other hand, mesenchymal cells proliferated from the transition zone and extended over the surface of the damaged cartilage. At the peripheral portion of the articular surface, they migrated and differentiated into chondrocytes with the formation of abundant intercellular matrix to produce hyaline cartilage. From these findings, it was apparent that mesenchymal cells in the transition zone were actively engaged in the repair of articular cartilage. PMID- 2878521 TI - Morphological alterations in distal and collecting tubules of the rat renal cortex after aminoglycoside administration at low doses. AB - Ultrastructural alterations in the cortical, distal and collecting tubules have been examined in female Sprague-Dawley rats treated with various aminoglycosides in clinical use. Gentamicin, dibekacin (10 mg/kg X day), netilmicin, tobramycin (4 or 10 mg/kg X day) or amikacin (37.5 mg/kg X day) were administered intraperitoneally twice a day over different periods of time, extending from 4 to 14 days. The kidney cortex was examined after 4, 7, 10 or 14 days of aminoglycoside administration by light (semithin sections) and electron microscopy. After 7 or more days of treatment, lysosomes in collecting tubular cells (and to a lesser extent in distal tubular cells) contained concentric lamellar material (myeloid bodies), an ultrastructural alteration typical of drug induced lysosomal phospholipidosis. Although this alteration appeared qualitatively similar to that observed in proximal tubular cells, it was less conspicuous and occurred later during treatment. In addition, distal tubular cells occasionally showed marked vacuolization and disruption of the basal cell architecture. The possible relationship between these alterations and the urine hypo-osmolality characteristic of aminoglycoside-induced renal dysfunction is discussed. PMID- 2878522 TI - S-100 protein expression in satellite and Schwann cells in neuroblastoma. An immunohistochemical and ultrastructural study. AB - Immunohistochemical evidence has recently been provided that in the normal adrenal medulla as well as in autonomic ganglia, satellite cells and Schwann cells react with S-100 protein antiserum. In the light of these data, we investigated primary peripheral neuroblastoma and ganglioneuroblastoma to determine firstly whether both cell populations actually exist in the malignancies, using the definite criteria of electron microscopy for their identification, and secondly whether they express S-100 protein using on immunohistochemical technique and light microscopy. The results indicate that in both neuroblastoma variants, satellite and Schwann cells are present and specifically express the S-100 antigen. PMID- 2878523 TI - Effect of hyperoxia on liver necrosis induced by hepatotoxins. AB - We have tested the effects of hyperbaric oxygen on necrosis of rat liver induced by the administration of several toxins. The extent of liver necrosis was determined 24 h after the administration of the toxins by measurement of serum levels of alanine and aspartate amino-transferases and by histologic and ultrastructural analyses. Treatment with hyperbaric oxygen decreases carbon tetrachloride (CCl4)-induced necrosis in a manner dependent upon duration and pressure of oxygen exposure. Pretreatment of rats with phenobarbital diminishes this protective effect. Hyperbaric oxygen treatment before or immediately after CCl4 intoxication is protective. Loss of protection is rapid; hyperbaric oxygen treatment 6 h after CCl4 intoxication augments the liver necrosis. No delayed necrogenic effects of CCl4 are seen in the animals treated with hyperbaric oxygen immediately. Hyperbaric oxygen augments the liver necrosis induced by acetaminophen, bromobenzene, dimethylnitrosamine or thioacetamide. This augmented necrosis is averted by prolonged treatment with hyperbaric oxygen. Hyperbaric oxygen has no effect on liver injury induced by galactosamine or lipopolysaccharide. We conclude that hyperoxia decreases the hepatic necrosis induced by compounds which undergo reductive biotransformation by the cytochrome P-450 monooxygenase system; hyperoxia augments the necrosis induced by compounds which undergo oxidative biotransformation by this system. Biotransformation of toxins appears to be nonspecifically inhibited by hyperoxic exposure of long duration. PMID- 2878524 TI - A comparative study of the gut-associated lymphoid tissue of primates and rodents. AB - Previous studies have suggested that the gut-associated lymphoid tissue (GALT) of man is distinct from that of laboratory animals, but it is not clear whether this is due to environmental or true species difference. We have made a comparative study of rats and baboons because, like rats, baboons are herbivorous and relatively unhygienic but they are phylogenetically much more closely related to man. The Peyer's patches of rats, baboons and man are morphologically very similar in all three species but phenotypically those of man and baboons are different to those of rats. Cells with irregular nuclei ("centrocyte-like" cells) surround the mantle zone in all three species. While these cells express surface IgD and IgM in rats, in man and baboons they express surface IgM or IgA. A population of immunoblasts which express cytoplasmic IgA are present in association with the high endothelial venules of rat Peyer's patches. These cells are not present to the same extent in man or baboons. This suggests that the events between the antigenic stimulation of Peyer's patches and the ultimate seeding of the lamina propria with IgA secreting plasma cells may be different in rodents and primates. PMID- 2878526 TI - The distribution and localization of the monoclonal antibody-defined antigen 19-9 (CA19-9) in chronic pancreatitis and pancreatic carcinoma. An immunohistochemical study. AB - The carbohydrate antigen 19-9 (CA19-9) is considered to be of great importance in the diagnosis, differential diagnosis and follow-up of human pancreatic carcinoma. CA19-9 antigen has been isolated and characterized as the oligosaccharide sialylazed lacto-N-fucopentaose II and a monoclonal antibody against CA19-9 is commercially available. In this immunochemical study we have examined the localisation and distribution of monoclonal anti-CA19-9 in pancreatic tissue obtained from 20 patients with a normal pancreas (lacking pancreatic tumour or evidence of inflammation), from 50 patients with chronic pancreatitis and from 50 patients with pancreatic carcinomas of various types. In the normal pancreas (free from tumour or inflammation) we found anti-CA19-9 to be localized in the branches of the pancreatic ducts with discontinuities predominantly at the apical surfaces of the lining epithelium. In chronic pancreatitis a continuous positive reaction was found in the small, medium and large ramifications of the pancreatic ducts. In ductal epithelium exhibiting mucoid transformation, a mosaic-like, discontinuous positive reaction was found, whereas in epithelium showing pseudopapillary and papillary hyperplasia a uniform positive reaction was obtained. Multilayered epithelium ("squamous metaplasia") was negative. The fluid content of any cysts present and the tubular accumulations found in chronic pancreatitis showed a positive reaction. The reaction in chronic pancreatitis differed from that in normal pancreas in its distribution but not in its intensity. All carcinomas of the exocrine pancreas showed intensely positive reaction in a very varied distribution whereas the anaplastic carcinomas gave a negative reaction. Whilst in chronic pancreatitis the binding of anti-CA19-9 was unimpressive and strictly localized, in exocrine pancreatic carcinomas binding was and strictly localized, in exocrine pancreatic carcinomas binding was very marked and diffuse in distribution. From this we conclude that malignant cells display a greater number of CA19-9 epitopes than cells in chronic pancreatitis. The difference can only be regarded as quantitative, since the immunohistochemical reaction does not allow qualitative discrimination between chronic pancreatitis and pancreatic carcinoma; CA19-9 should not be therefore termed a "tumour marker". The glycoprotein nature of CA19 9 was confirmed by sialidase and chemical desialylation. PMID- 2878525 TI - Glomerular sclerotic lesions in the rat. Histochemical analysis of their macromolecular and cellular composition. AB - The present study provides a histochemical analysis of the macromolecular and cellular composition of focal and segmental glomerular hyalinosis and sclerosis (FSGHS) in the rat with special reference to the different types of lipids present and to the participation of monocytes. FSGHS was induced in male Wistar rats by unilateral nephrectomy (UN) or puromycin aminonucleoside (PAN) injections. Histochemical analysis of glomeruli with FSGHS in both models after 20 weeks of proteinuria revealed massive deposits of lipids. These lipid accumulations were shown to consist mainly of free and esterified cholesterol; triglycerides and phospholipids were present in small amounts. Monocytes, identified by the alpha-naphthyl acetate method for non-specific esterase activity were scanty in glomeruli affected by FSGHS with an average glomerular count of 0.1 in UN- and 0.2 in PAN-treated rats. When present, no preferential localization of monocytes in the lesions was observed. The progressive glomerular damage occurring once the process of hyalinosis and sclerosis has started may be related to the paucity of "scavenging" monocytes. Cholesterol may be one of the substances involved in the development of these glomerular changes. PMID- 2878527 TI - Localization of endogenous lectins in normal human breast, benign breast lesions and mammary carcinomas. AB - Specific antisera against three mammalian beta-galactoside-specific lectins of apparent molecular weights 14.5 kDa, 18 kDa and 29 kDa have been used to localize these lectins in normal breast, and in benign and malignant mammary lesions. In normal breast tissue discrete localization of two lectins (Mrs 14.5 kDa and 18 kDa) was demonstrated in fibroblasts, smooth muscle cells, myoepithelial cells and capillary endothelium. Extracellular localization of one lectin (Mr 14.5 kDa) in collagen was apparent. The third lectin (Mr 29 kDa) labelled preferentially luminal cells and their secretory product. Two benign tumours (an analyzed fibroadenoma and a papilloma) revealed strong staining with two lectins (Mrs 18 kDa and 29 kDa). Of the 24 mammary carcinomas examined, the lectin (Mr 14.5 kDa) was expressed by only occasional tumour cells, the lectin (Mr 18 kDa) occurred in many tumour cells and the lectin (Mr 29 kDa) labelled tumour cells in nearly all cases. The expression of these beta-galactoside-specific endogenous lectins therefore appears to be regulated differently in normal breast compared with mammary tumours. PMID- 2878528 TI - Histochemistry of small intestinal dysplasia in familial polyposis coli. AB - Biopsies of duodenal and ileal mucosa from patients with familial polyposis coli were studied. Areas of atypia were identified in the duodenum of six patients and in the ileum of three patients. Grade I atypia was characterized by crowding and elongation of cells and nuclei, a slight reduction in the number of goblet cells and the presence of a brush border; grade II atypia was further characterized by pseudo- or pluristratification of cells, a marked reduction in the number of goblet cells and the absence of a brush border. In areas of atypia, columnar cells often contained PAS-positive apical granules, which were diastase-resistant and unstained by alcian blue at any pH; the brush border, even where recognizable in haematoxylin-eosin and PAS-stained sections, was unreactive histochemically for alkaline phosphatase. Goblet cells were few in areas of atypia, but those present were regularly stained by PAS and alcian blue pH 2.6. Apical granules, similar in their histochemical characteristics to those observed in columnar cells in areas of atypia, were also found in otherwise normal mucosal areas, even in some patients with no overt areas of atypia in the biopsies studied. These granules have been interpreted as an abnormality, possibly preceding the onset of atypia. Hyperplasia of goblet cells, secreting mucins with the same staining pattern as in normal intestine, was found in some patients, either adjacent to areas of atypia or independent of them. Intervening columnar cells had a normal morphology, alkaline phosphatase-reactive brush borders and no sign of mucus secretion. This goblet cell hyperplasia has been interpreted as a reactive, nonspecific alteration of the mucosa. PMID- 2878530 TI - Spatial distribution of Langerhans' cells and T-lymphocyte subpopulations in human tympanic membrane and aural cholesteatoma. AB - Immunohistochemical analysis of human cholesteatoma matrices revealed the presence of Langerhans' cells and T-lymphocytes. Through cell-to-cell interaction, Langerhans' cells probably play a key role in skin-related disorders, including cholesteatomas. They probably originate from a mobile cell population of monocyte origin and migrate into and out of the body's lining. Their custodial function is often carried out in close relation with T lymphocytes. Monoclonal antibodies against Langerhans' cells and T-lymphocyte membrane receptors reveal the presence of these cell populations in cholesteatoma matrices but not in the tympanic membrane. Langerhans' cells and T-cell "traffic" through cholesteatomas are discussed in relation to the pathogenesis, natural course and recurrence of cholesteatomas. Through immunopathologic evaluation the clinical aggressiveness of a cholesteatoma may become predictable. It may even have consequences for the future handling of cholesteatomas. PMID- 2878529 TI - Immunoreactivity for S-100 protein in dendritic and in lymphocyte-like cells in human lymphoid tissues. AB - S-100 protein is an immunohistochemical marker for a subset of dendritic cells, the interdigitating reticulum cells (IDRCs), which are mainly located in T dependent areas of lymphoid tissues. In the present study we have investigated the distribution of S-100-positive cells in lymph nodes, spleen, thymus and peripheral blood of normal subjects. Immunoreactivity for S-100 protein was demonstrated in large cells with dendritic morphology and in small lymphocyte like cells present in the lymph node paracortex, thymic medulla, splenic periarterial lymphatic sheaths (PALS) and in peripheral blood. S-100-positive lymphocyte-like cells were frequently detected around high endothelial venules (HEV) and were present in numbers comparable to those of S-100-positive IDRCs. Immunoelectron microscopy confirmed the existence of positive cells with lymphoid morphology and revealed that the intracellular distribution of the immunoreaction product was similar in lymphoid and dendritic cells. Further characterization of S-100-positive cells demonstrated that both lymphoid and dendritic cells were unreactive with a large panel of monocytic and macrophage markers. PMID- 2878531 TI - Ultracytochemistry of pancreatic damage induced by excess lysine. AB - The ultracytochemical changes induced in the pancreas by a single large dose of lysine (400 mg/100 g body weight) were studied in male Wistar rats of 7 weeks old. The first changes in the acinar cells were marked swelling of mitochondria with increase in their calcium content and decrease in their ATP content. Early calcium deposits seemed to occur in the matrices of swollen mitochondria and later various patterns occurred. These findings suggested that damage of the acinar cells by excess lysine resulted in breakdown of the mitochondrial membrane barrier to calcium as a very early abnormality, and that extracellular calcium then entered the mitochondrial matrices and inhibited mitochondrial function. Subsequently focal areas of the cytoplasm were degraded. Autophagic vacuoles appeared in these areas, and then acid phosphatase activity in their periphery as a result of fusion with lysosomes. The reaction of acid phosphatase was demonstrated in the locally degraded rough endoplasmic reticulum within or around autophagic vacuoles, suggesting that the endoplasmic reticulum as well as lysosomes participated in the intracellular degradation of cytoplasmic organelles in damaged acinar cells. PMID- 2878532 TI - Identification of fibronectins in peritoneal macrophages during the phagocytosis of Brucella. An immunocytochemical study by electron microscopy. AB - Fibronectin is a high-molecular-weight molecule whose opsonic properties favor the endocytosis of bacteria and particulate material. Using immunolabeling with anti-fibronectin IgGs coupled with peroxidase, we have looked for its localization in peritoneal macrophages from antigenically stimulated and nonstimulated mice. Ultrastructural location of fibronectin in macrophages sheds light on several points. It confirms that it is synthesized and secreted by mouse peritoneal macrophages. In addition, we found significant variability among the cells of a given population, and also between populations from stimulated and nonstimulated animals. Under certain conditions macrophages secrete an extracellular matrix whose aspect varies with the physiological conditions, but which generally consist of fibronectins either on a fibrillar network connecting the macrophages to one another or in an agglutinating extracellular cement. Endocytosis of Brucella by macrophages is accompanied by secretion of fibronectin inside endocytic vacuoles; this secretion contributes to the formation of an electron-dense material closely surrounding phagocytosed bacteria. PMID- 2878533 TI - Fatty degeneration in cultured hepatocytes. A new experimental model. AB - In co-cultures of adult rat hepatocytes and a neonatal rat liver cell line, severe fatty degeneration was induced by the addition of 50% rat serum. The light and electron microscopic patterns did not differ significantly from those of in vivo fatty degeneration and the changes were reversible on removal of the serum. The in vitro system is considered to simulate some forms of fatty degeneration of the liver and to be suitable for testing the effects of liver-protecting agents. PMID- 2878534 TI - Expression of glial fibrillary acidic protein by neoplastic cells of mullerian origin. AB - Immunocytochemical studies of malignant mixed Mullerian tumors revealed the presence of neoplastic cells showing strong immunoreactivity for glial fibrillary acidic protein, a protein specific for astrocytes, in 9 of 13 cases. Undifferentiated malignant tumor cells of endometrial stromal sarcoma and astrocytes in glioma of the uterus also demonstrate GFAP immunoreactivity. GFAP immunostaining in these neoplastic cells is highly specific and shows no cross reactivity with cytokeratin, actin, myoglobin, epithelial membrane antigen or factor VIII. It is postulated that the GFAP immunostaining within neoplastic cells of Mullerian origin may be a reflection of the phenotypic diversity of intermediate filament proteins that can be expressed by malignant neoplastic cells, that the polypeptides of GFAP may be heterogeneous, that there may be an ontogenic relationship between the cells of Mullerian origin and neuroectodermal cells, or that this may represent neometaplasia of Mullerian cells. PMID- 2878535 TI - Ultrastructure of amyloid fibrils in Alzheimer's disease and Down's syndrome. AB - Amyloid fibrils in brains of patients with Alzheimer's disease and Down's syndrome were examined by light and electron microscopy. In addition, replicas of amyloid fibrils produced by a quick freezing method from the brain of a patient with Down's syndrome were examined by electron microscopy. The amyloid fibrils were shown to consist of hollow rods. These were composed of filaments arranged as a tightly coiled helix, each turn of which consisted of five globular subunits. This structure appears to be similar to the prion filament observed in Creutzfeldt-Jakob disease (CJD). The possibility therefore arises that amyloid fibrils in Alzheimer's disease and Down's syndrome may be related to the transmissible agents responsible for diseases such as CJD, kuru and Gerstmann Straussler Syndrome (GSS). PMID- 2878536 TI - [Humoral mechanisms of the action of galvanic current and ultrasound]. PMID- 2878537 TI - Pulmonary dirofilariasis in humans--pneumonitis that evolved to a lung nodule. PMID- 2878538 TI - [Possibilities of psychological preparation for surgery in children and adults]. AB - Research in the field of behavioural medicine concerning psychological preparation for surgery is beginning to focus on practical issues. In the first study sixty children between the ages of 4 and 8 received the usual medical preparation from the hospital staff. In addition, the patients of two treatment groups were provided with relevant information by presenting a photographic peer model, or received emotional support by a psychologically trained supervisor. The second study was designed to assess the anxiolytic effects on preoperative state anxiety in 40 adult in-patients by implementing a systematic desensitization program. As a main result the findings demonstrated the sensitizing effects of psychological preparation for surgery both in children and adults. Contraindications and resulting practical issues are discussed. PMID- 2878539 TI - [Depression and Parkinson syndrome]. AB - Depressive mood is frequently associated with Parkinson's syndrome, but it may also occur as a precursor of this disease. As regards the subtypes of Parkinson's disease, the frequency of depressive states is significantly higher in the type dominated by akinesia and rigidity than in the type dominated by tremor. On the basis of biochemical changes, certain aspects of the depression can be successfully treated by substitution therapy: L-dopa medication may increase the reduced dopamine values in the striatum, thereby improving drive. Substitution with L-tryptophan raises the lowered serotonin values in the reticular formation, which may influence sleep disturbances. The changes of basic mood, however, which are characteristic of depression, such as cheerlessness and apathy, are the dopamine of antidepressive medication; only these drugs can re-establish the biochemical balance to a large extent. PMID- 2878540 TI - [Neurobiologic and pharmacologic studies on the pathogenesis of Parkinson disease]. AB - Parkinson's disease is characterized especially by a degeneration of pigmented brain regions, like substantia nigra. These changes are accompanied by a variety of biochemical disturbances of dopaminergic and noradrenergic systems. Also the reduction of serotonin can be related to degenerative processes occurring in subareas of the raphe. Furthermore amino acid transmitters like GABA and a variety of peptidergic neuromodulators are changed. Additional cholinergic hypofunction due to degeneration of the nucleus basalis Meynert is able to impair the quality of life due to loss of intellectual capacity. A variety of biochemical mechanisms compensate for a long time the progression of neuronal loss. Modern treatment strategies (combined L-dopa therapy, dopaminergic agonists, MAO-B inhibitors, amantadine) are able to substitute the deficiency especially of the catecholamines. For the development of more causal therapies, a new animal model has been developed 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes parkinsonism after peripheral administration and leads to denervation of the dopaminergic nigrostriatal system. It is the hope that this new model, which is described here in detail, will lead to decisive data underlying the cause of Parkinson's disease. PMID- 2878542 TI - [Plasma soldering--why?]. PMID- 2878541 TI - [Significance of endothelial cells for the regulation of the tone of smooth muscle--formation of an endothelial, relaxing factor]. AB - Vascular endothelium is not only a mechanical, non-thrombogenetic barrier in the blood vessel wall, but probably plays a substantial role in the regulation of vascular smooth muscle tone. Besides the ability to metabolize vasoactive compounds like catecholamines and angiotensins, endothelial cells possess an active biochemical machinery for the production of vasoactive compounds (e.g. prostacyclin). During recent years it has become apparent that a large variety of vasodilator compounds require intact endothelial cells to exert their relaxing action. These endothelium-dependent relaxations are not mediated by prostacyclin of endothelial origin, but by an unknown substance that is referred to as endothelium-derived relaxing factor (EDRF). EDRF is a chemically unstable humoral substance and has a biological half-life in the range of seconds. Although EDRF is not a prostaglandin or leukotriene, several findings suggest possible relationships of its production with the eicosanoid system. Both stimulation of phospholipase A2 and inhibition of lysolecithin acyltransferase induce the production of EDRF. This suggests that cleavage of phospholipids may be an important step in the formation of EDRF. EDRF-mediated vascular relaxations (like relaxations induced by nitrovasodilators) were found to be associated with increases in cyclic GMP in vascular smooth muscle. Endothelial cells produce a factor that directly stimulates the enzymatic activity of soluble guanylate cyclase. Several points of evidence indicate that this factor may be identical with EDRF. Thus the mechanism of action of the EDRF formed endogenously may be similar to that of nitrovasodilators.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878543 TI - [Sorption capacity of polystyrene plates used in immunoenzyme analysis]. AB - The data indicating that the degree of sorption of the antigen onto the plate depends on the duration of this process are presented. As shown in this investigation, the lower the adsorption activity of the plates, the longer the process of the sensitization of plates with the antigen. The process of the sorption of the antigen onto the plates with low adsorption capacity may be accelerated by sensitizing the plates at different temperatures. Besides, the adsorption capacity of the plates was increased by ultraviolet irradiation. PMID- 2878544 TI - [Dengue hemorrhagic fever in the developing countries of southeast Asia]. PMID- 2878545 TI - One-electron activation in ATP synthesis. PMID- 2878546 TI - Neurotransmitter uptake by the central nervous system of fresh-water mussel (Anodonta cygnea L): I. In vitro uptake of serotonin, dopamine and noradrenaline. AB - The accumulation of serotonin, dopamine and noradrenaline in the cerebral, pedal and visceral ganglia is mediated by a high-affinity (uptake 1) and a low-affinity (uptake 2) system. This uptake mechanism is dependent on time and temperature. The monoamine uptake systems in the cerebral, pedal and visceral ganglia are not identical. At low external serotonin concentration, the cerebral ganglia display twice the rate of uptake 1 as compared to the visceral and pedal ganglia. PMID- 2878547 TI - Neurotransmitter uptake by the central nervous system of fresh-water mussel (Anodonta cygnea L): II. Effects of various drugs, amines and ions. AB - The high-affinity uptakes of serotonin, dopamine and noradrenaline by the cerebral, pedal and visceral ganglia of fresh-water mussel were inhibited by the presence of other amines. Reserpine was the most potent inhibitor among the drugs tested. Chlorpromazine seemed to be a specific inhibitor of serotonin uptake. It did not affect the accumulation of dopamine and noradrenaline. Ouabain had an inhibitory effect only at relatively high concentrations. Lack of sodium greatly diminished the rates of accumulation of serotonin and dopamine, but had less effect on the uptake of noradrenaline. PMID- 2878548 TI - A comparison of porcine and human thyroid tissue in the assay of thyroid stimulating immunoglobulins. AB - The central role of Thyroid Stimulating Immunoglobulins (TSI) in the pathogenesis of the hyperthyroidism of Graves' disease has become generally accepted and a wide variety of assays for the detection of these antibodies has been developed. The dependence on the availability of human thyroid tissue makes most of these assays unsuitable for routine clinical use, a problem circumvented by the use of nonhuman thyroid tissue in some TSI assays. We therefore compared porcine and human thyroid tissue in a TSI assay based on in vitro cAMP generation. No major differences in within and between run variation were found and, with some notable exceptions, a reasonable correlation could be demonstrated between the results in both assays (R = 0.89, P less than 0.001). However, the sensitivity of the porcine TSI assay is only 60% of the estimated sensitivity of the human TSI assay. In spite of the practical advantages this porcine TSI assay, and possibly also other TSI assays using non-human thyroid tissue, cannot totally replace human TSI assays. The value of these assays in predicting the outcome of medical treatment of Graves' disease remains to be established. PMID- 2878549 TI - Effect of human chorionic gonadotropin on luteinizing hormone and prolactin binding by testes of bilaterally cryptorchid rats. AB - This study investigates the ability of the testis in the cryptorchid state to bind luteinizing hormone (LH) and prolactin (Prl). For this purpose, rats were made bilaterally cryptorchid at 21 days of age; sham-operated rats were used as controls. At 56 days, the animals were injected with saline or with increasing doses of human chorionic gonadotropin (hCG: 1, 10 or 100 IU) and killed 8 or 24 h after injection. Cryptorchidism and injection of hCG did not alter plasma Prl levels. In cryptorchid rats, both LH and Prl binding expressed in pmol/testis were lower than in sham-operated controls (about 75% and 65%, respectively), but unchanged (LH binding) or increased (Prl binding) when expressed in pmol/g testis. In controls, 100 IU hCG induced a significant decrease in LH binding at 24 h. Prl binding was also significantly lower in controls injected with 100 IU hCG than in those injected with 1 or 10 IU hCG, at 8 h. In cryptorchid rats injected with 100 IU hCG, the LH binding fell 8 h and 24 h after injection; at 24 h, hCG reduced Prl binding. In conclusion, there was a considerable decrease in LH and Prl receptors in the abdominal testes. The negative regulation of these receptors in response to hCG was maintained, but at times and for doses which differed from those observed in scrotal testes. PMID- 2878550 TI - Cushing's syndrome and autonomous thyroid nodules, a variant of multiple endocrine neoplasia? AB - Over a 20 year period 4 of 40 (10%) female patients with Cushing' syndrome also had a solitary thyroid nodule. In 3 cases this was an autonomous 'hot' nodule. In the same population only one case of presumed Graves' disease was seen. It is postulated that the association of autonomous thyroid nodule and Cushing's syndrome may represent a variant of multiple endocrine neoplasia. PMID- 2878551 TI - Somatostatin plasma levels and biological effects following subcutaneous administration of somatostatin in man. AB - The rate at which somatostatin appears in the circulation after subcutaneous bolus injection and continuous administration by pump was determined in normal subjects by serial radioimmunoassays of immunoreactive somatostatin. Following a single subcutaneous injection of 250 micrograms, the somatostatin peak in plasma appeared after 5 min and had only a transient effect on insulin levels. During continuous administration, somatostatin reached levels able to reduce significantly insulin and glucagon. Somatostatin plasma levels exerting biological effects were observed during the subcutaneous administration of the peptide. PMID- 2878552 TI - The prevalence of immunological abnormalities in endemic simple goitre. AB - Thyroid growth stimulating immunoglobulins microsomal antibodies and antibodies against thyroglobulin were determined in patients with simple goitre (n = 20) and controls (n = 6) living in an iodine deficient area. In addition, lymphocytic infiltration of thyroid tissue, the amount of the various lymphocyte subsets (Leu 4+, Leu 3a+, and Leu 2a+ T-cells as well as B1+ B cells) in the thyroid gland, as well as the expression of the histocompatibility antigen HLA-DR on thyrocytes and intrathyroidal T-lymphocytes were examined. Goitrous patients were subdivided into two groups according to their individual iodine supply estimated by iodine excretion values, and immunological parameters were compared between patients with low (group A, iodine excretion less than 70 micrograms/24 h) and with higher (group B, iodine excretion greater than 100 micrograms/24 h) iodine supply. Thyroid growth stimulating immunoglobulins and antithyroid antibodies were equally prevalent in the two patient groups, but were absent in controls. Lymphocytic infiltration of thyroid tissue was present to a comparable extent in patients of groups A and B, but to a distinctly lower degree in control persons. Intrathyroidal T-lymphocyte subsets did not differ between patients and controls. B-lymphocytes, germinal centres as well as DR+ thyrocytes were detected in goitrous patients of both groups, but never in control persons. Thus, immunological abnormalities frequently occur in patients with simple goitre and do not depend upon individual iodine supply. PMID- 2878553 TI - Thyroid hormone-catecholamine interrelationship during cold acclimation in rats. Compensatory role of catecholamine for altered thyroid states. AB - Effects of hyper- and hypothyroidism on catecholamine (CA) metabolism in the brain, adrenal glands, liver, and brown adipose tissue (BAT) were studied in adult rats during cold acclimation. Hypothyroidism was induced by the administration of propylthiouracil (PTU) and hyperthyroidism by the injection of thyroxine (T4). After 2 weeks of treatment, they were exposed to cold (5 degrees C) and sacrificed after 1 or 4 weeks. Although the body weight gain of PTU treated rats were markedly impaired, the body temperature was maintained within normal range. They had increased cerebral dopamine, adrenal CA and BAT norepinephrine (NE) contents, enhanced cerebral tyrosine hydroxylase and adrenal dopamine beta-hydroxylase (DBH) activities and elevated [3H]dihydroalprenolol (DHA) binding to liver plasma membranes (P less than 0.01 vs controls). T4 treated rats showed an increased brain and adrenal CA only after cold exposure. The BAT NE content, DHA binding to liver plasma membranes, and [3H]guanosine diphosphate binding to BAT mitochondria were reduced by 30 to 50% from control values after 4 weeks of cold exposure. These results indicate that during cold acclimation, thyroid hormone deficiency is associated with an accelerated CA synthesis and release, which results in an enhanced BAT thermogenesis, and the hyperthyroid state suppresses CA release, hepatic DHA binding, and BAT heat production. Thus, there is a close metabolic interrelationship between thyroid hormone and CA during exposure to cold. CA appears to ameliorate thyroid hormone excess or deficiency. PMID- 2878554 TI - Prolactin (PRL) inhibiting substance in seminal plasma of infertile patients. Preliminary results. AB - The role of PRL in the control of the mechanisms of regulation of testicular function is still unclear. Indeed, hyperprolactinemia is usually associated with male hypofertility. Several studies have demonstrated that human seminal plasma (HSP) contains radioimmunoassayble PRL and than testis and prostate possess membrane receptors for PRL (Charreau et al. 1977; Aragona et al. 1977). Recently Demoulin and Franchimont have observed, in HSP, the presence of a substance capable of inhibiting PRL secretion by isolated rat pituitary cells (Demoulin et al. 1978). They abbreviated it SPIF (seminal plasma PRL inhibiting factor). The inhibition of PRL secretion was significant for concentrations equal to or higher than 4.2 l of HSP/ml of culture medium. This non steroidal substance is thermostable and trypsin resistant; the molecular weight is less than 10,000 Daltons. In this work, we have compared the SPIF activity with basal levels of LH, FSH, PRL, Testosterone and, after stimulation, in the serum of patients affected with various fertility problems. PMID- 2878556 TI - Expression of dipeptidylaminopeptidase-IV in some human T and B cell lines. AB - The specificity of the expression of dipeptidylaminopeptidase-IV (DAP-IV) was examined in cells from leukemia patients and in 33 normal and leukemic human cell lines widely used in various studies. There was no correlation between DAP-IV activity and OKT4 positivity or maturation stage in T cells. In addition, DAP-IV was unexpectedly expressed by 4 B cell lines and 1 histiocytic lymphoma cell line, indicating either lack of specificity of DAP-IV or infidelity of gene expression under unnatural culture environment. PMID- 2878557 TI - Alterations in ornithine decarboxylase and transglutaminase activities in lymphocytes from untreated patients with chronic lymphocytic leukemia. AB - Ornithine decarboxylase (L-ornithine carboxylase, EC 4.1.1.17) and transglutaminase (R-glutaminylpeptide: amine gamma-glutamyltransferase, EC 2.3.2.13), enzymes implicated in the regulation of growth processes, were studied in lymphocytes from untreated patients with chronic lymphocytic leukemia. A marked increase of ornithine decarboxylase activity was found in lymphocytes from chronic lymphocytic leukemia patients when compared to normal human lymphocytes; in contrast, no transglutaminase activity was found in lymphocytes from untreated patients with chronic lymphocytic leukemia. PMID- 2878555 TI - [In vivo evaluation of the effect of antacids and H2 receptor blockaders on the intragastric pH in gastric and duodenal ulcer]. AB - The aim of this work is to establish the best treatment for patients with gastric and duodenal ulcer, by measuring the effects of antiacids and H2-receptor antagonists on gastric pH. 16 patients were studied: 9 of them had a duodenal ulcer, 2 a gastric ulcer and 5 had both. All the patients remained fasting and receiving no drug for 24 hrs. During this 24 hrs., a nasogastric tube was inserted into the stomach and the gastric content was obtained by aspiration each hour from 8 A.M. to 8 P.M. Three days after, each patient received a daily dose of 1 g of Cimetidine, and the whole procedure was repeated. The same was done with 300 mg of Ranitidine daily, 150 ml of Al-Mg antiacids daily, and at last, the same procedure was performed with the association of Ranitidine and Al-Mg antiacids at the mentioned dosage. For the statistical analysis of the data, the mean ordinate of the pH was used as a representative value of each individual's pH. Individual differences (pH with treatment minus pH without treatment) were obtained. The mean effect of each treatment was obtained averaging that differences. For comparison among different drugs, the same procedure was used. Student's paired t tests were performed in a signification level. The buffering capacity was measured in the following way: The percentage of the gastric secretion samples with pH equal or higher than 4 in each treatment and in the total number of patients was confronted with the results obtained in the same patients with no treatment. All the drugs were useful for buffering the gastric acidity, but in different intensity. The association of Ranitidine and Al-Mg antiacids showed to be the most efficient statistically when compared with Cimetidine and Al-Mg antiacids; no statistical difference appeared in the comparison with Ranitidine. PMID- 2878558 TI - Pretreatment technique for fast intubation with vecuronium: intubation conditions and unwanted effects. AB - In eighty patients 15 micrograms kg-1 of vecuronium was given 3 minutes before induction of anesthesia and 50 micrograms kg-1 was given at the time of induction. The trachea was intubated 60 seconds after the second dose. A wide spread of twitch depression was found. The 80 patients were divided into 4 groups retrospectively with respect to the degree of neuromuscular blockade during intubation. Tracheal intubation was performed when the mean twitch depression was 48.8 +/- 11.8 (SD)% and the conditions were satisfactory in 89% of the cases. Intubating conditions were different significantly between the four sub-groups (p less than 0.01). Ptosis occurred in 77 patients, diplopia in 13 patients and dyspnea in 2 patients between the first injection of vecuronium and induction of anesthesia. The administration of vecuronium in divided doses gives satisfactory intubating conditions in the majority of the patients, but close observation between the priming dose and the induction of anesthesia is mandatory. The method is not considered suitable for obese and is probably not indicated in severely ill patients. PMID- 2878559 TI - Assessing the results of treatment of chronic heart failure. PMID- 2878561 TI - Limbic seizures induced by systemically applied kainic acid: how much kainic acid reaches the brain? PMID- 2878560 TI - Endogenous excitotoxins as possible mediators of ischemic and hypoglycemic brain damage. PMID- 2878562 TI - Excitatory amino acids and the blood-brain barrier (BBB). PMID- 2878563 TI - Homocysteic acid, an endogenous agonist of NMDA-receptor: release, neuroactivity and localization. PMID- 2878564 TI - Excitatory amino acid pathways in the brain. PMID- 2878565 TI - Cortical and subcortical afferents of the amygdaloid complex. PMID- 2878567 TI - Acidic excitatory amino acids and seizures: neurochemical interrelationships. PMID- 2878566 TI - Acidic peptides in brain: do they act at putative glutamatergic synapses? PMID- 2878568 TI - Excitatory amino acids and regenerative activity in cultured neurons. PMID- 2878569 TI - Evidence for the activation of the N-methyl-D-aspartate receptor during epileptiform discharge. PMID- 2878570 TI - Blockade by D-aminophosphonovalerate or Mg2+ of excitatory amino acid-induced responses on spinal motoneurons in vitro. PMID- 2878571 TI - Putative amino acid transmitters in the amygdala. PMID- 2878572 TI - Transition metal ions in epilepsy: an overview. PMID- 2878573 TI - Relationship of glutamic acid and zinc to kindling of the rat amygdala: afferent transmitter systems and excitability in a model of epilepsy. PMID- 2878575 TI - A survey of the anatomy of the hippocampal formation, with emphasis on the septotemporal organization of its intrinsic and extrinsic connections. PMID- 2878574 TI - On the role of seizure activity and endogenous excitatory amino acids in mediating seizure-associated hippocampal damage. PMID- 2878577 TI - Seizures and brain damage: are excitatory amino acids involved? PMID- 2878576 TI - Glutamate and anoxic neuronal death in vitro. PMID- 2878578 TI - Characterization of dopamine D-1 and D-2 receptors. PMID- 2878579 TI - Biochemical and behavioral studies of D1 dopamine receptors utilizing SCH 23390. PMID- 2878581 TI - Oligonucleotide fingerprint analysis on Japanese encephalitis virus strains isolated in Japan and Thailand. AB - Genetic variation in Japanese encephalitis (JE) virus isolates from Japan and Thailand was examined by oligonucleotide fingerprints of the 42S genome RNA. Japanese isolates were rather similar to each other, as were the recent isolates from Thailand. However, recent Thai isolates were significantly different from recent Japanese isolates. From these results it was presumed that mutations and selections of the JE virus genome would have progressed independently in these geographically distant areas. PMID- 2878580 TI - The dopamine D1 receptor: biochemical and behavioral aspects. PMID- 2878582 TI - Characterization of the continuous green monkey spleen cell line 455. AB - A continuous line of adult green monkey spleen cells has been established and designated 455 (according to the number of animal). Cell suspension for primary explantation has been prepared by perfusion and disaggregation of the organ. The obtained culture, which consisted of fibroblast-like cells with chromosome modal number 60, underwent 25 passages followed by ageing and death (line 455 D). At passage level 13 in 2 culture flasks with 455 D cells, islets of polygonal cells had developed within 35 days; they gave rise to a continuous cell line with chromosome modal number 110 (designated line 455). Line 455 has a high proliferative activity but low demands on the composition of culture media and it can be easily passaged with the bovine serum at concentration of 1-5%. It is highly sensitive to a number of viruses. It is not contaminated with bacteria, fungi, mycoplasmas or viruses, it does not have a tumourigenic activity. Hence, it is a promising cellular model for virological studies, in particular, for preparation of inactivated vaccines along with Vero and 4647 cells. The line 455 can be used for investigation of the problems of haemopoiesis and immunogenesis. PMID- 2878583 TI - Comparative studies on growth of foot-and-mouth disease virus types 0 and Asia 1 in BHK-21 Razi cells. AB - Growth pattern of foot-and-mouth disease virus types 0 and Asia 1 in BHK-21 Razi cells was compared; while type 0 virus grew in high titre, Asia 1 virus was produced in low titre. Inhibition of host protein synthesis in type 0 virus infected cells was more pronounced than in Asia 1 virus-infected cells. Foot-and mouth disease virus type 0 infected cells showed higher lactic dehydrogenase activity when compared to Asia 1 virus. A significant decrease in virus yield was observed when Actinomycin D had been added at 50 micrograms/ml to infected cells. PMID- 2878584 TI - Detection of measles-specific IgM antibodies: comparison of 2-mercaptoethanol treatment, density gradient centrifugation, protein A-sepharose affinity chromatography, ion-exchange chromatography and haemadsorption techniques. AB - The sensitivity, specificity and effectivity of 5 methods for detection of measles-specific IgM antibodies were compared. A total of 371 sera from non immunized as well as immunized measles patients was included into the study. The highest positive rate was achieved by the haemadsorption-immunosorbent (HIST) test. The density gradient (DG) centrifugation and the ion-exchange chromatography (IERCR) were 10-15% less effective. Protein A-Sepharose affinity chromatography (ACR) and 2-mercaptoethanol (2-ME) treatment showed positive results in the half of samples which had been positive in the HIST. The titres were in significant correlation (r = 0.90 to r = 0.8793 at P = 0.01). Specificity and reproducibility of the tests were good. Rheumatoid factor did not influence the results. In general, HIST was found as most sensitive and effective. PMID- 2878585 TI - Postinfection and postvaccination antirubella immunity. AB - Out of 1670 pregnant women contacts examined for antibodies to rubella virus, recent rubella infection was confirmed in 5.1% of subjects, 2.2% of which were symptomatic and 2.9% asymptomatic; 89.9% of tested women were seropositive. These results closely resembled those, obtained in serological surveys, carried out in Poland several times in the years 1969-82. Rubella antibodies were found in over 90% of women in childbearing age, with HI antibody geometric mean titre (GMT) 58.7-84.3 (depending on the epidemiologic situation). Especially high GMT--of 122 -was detected in women of the 30-34 year age group after the rubella epidemic in 1980/81, which showed the highest rubella morbidity of 5-9 year-old children. Reactogenicity and immune response in 10-13 year-old vaccinated girls were investigated. Seroconversion among seronegatives, among subjects with low antibody level (less than 1:20) and among seropositives with antibody titres 40 or higher before vaccination occurred in 99.8%, 60% and 12.8% of cases, respectively. HI antibody GMT after immunization was 132.6-135, similar to GMT induced by naturally acquired infection in the women of 30-34 year age group after the rubella epidemic. The difference of GMT in vaccinated girls with joint symptoms (152) and without postvaccinal reactions (124) was statistically significant. Practical conclusions for rubella diagnostic and vaccination programmes based on the analogies and differences of antirubella immunity in infected pregnant women, in naturally infected children and adults, and in vaccinated subjects are discussed. PMID- 2878586 TI - Experimental pathogenesis of buffalo pox virus in rabbits: clinico-pathological studies. AB - Buffalo pox virus produced typical pock lesions on the skin of rabbits at the site of primary inoculation following an incubation period of 48-72 hr. Gross lesions in internal organs, characterized by focal or diffuse necrotic areas on lung, liver and spleen were seen from day 5 post-inoculation (p. i.). Isolated lesions of approximately 2 mm diameter appeared in skin, stomach, intestine and uterus from day 7 p. i. Histopathological changes, i. e. intra-alveolar and intra bronchial haemorrhages were seen in lungs and severe fatty changes were found in the liver. Multinuclear cells were detected in liver during recovery. Virus particles were demonstrated by electron microscopy in skin, lung, liver and spleen lesions. PMID- 2878587 TI - Peculiarities of tick-borne encephalitis virus reproduction in Haemaphysalis inermis ticks and their explants. AB - Virological, electron microscopic and immunomorphological investigation on the reproduction of tick-borne encephalitis (TBE) virus in Haemaphysalis inermis ticks and in tissue explants from nymphs during their metamorphosis revealed that the virus reproduced in the cells of different tissues and organs of ticks which were in different phases and stages of life cycle. During the eclipse phase of TBE virus persistence in ticks, when no virus could be demonstrated by infectivity assay, viral particles were detected by electron microscopy. PMID- 2878588 TI - Preparation and efficacy of antiherpes type 1 and 2 subunit vaccines. AB - DNA free antiherpes subunit vaccines were prepared from diploid human embryonic lung cells infected either with type 1 or type 2 herpes simplex viruses (HSV). Virion and membrane-bound virus-specific glycoproteins were solubilized with Nonidet P-40 and separated by ultracentrifugation. The antigenic properties of the vaccine were tested in guinea pigs. Antibody response was followed by virus neutralization and complement fixation. The vaccine itself was low-immunogenic, however its immunogenicity has considerably increased by usage of suitable adjuvants. In virus neutralization test higher antibody titre was found against homologous virus. The antibody response was related to protein content and to the frequency of vaccination. PMID- 2878589 TI - Avalon virus, Sakhalin group (Nairovirus, Bunyaviridae) from the seabird tick Ixodes (Ceratixodes) uriae White 1852 in France. AB - Nine strains of Avalon virus were isolated from Ixodes uriae ticks collected in the Cape Sizun seabird reserve, Brittany, from 1979 to 1985, during a longitudinal study of consequences of tick-borne infections for kittiwakes (Rissa tridactyla). Avalon virus strains isolated in France proved difficult to study owing to the weak infectious titres they exhibited in suckling mice or cultured cells. However, some interesting data concerning the ecology of virus infection and the morphology of the virions were obtained and are discussed. PMID- 2878591 TI - Peculiarities of Rickettsia prowazekii in the cell culture as revealed by cryoultramicrotomy. AB - Ultrastructure of Rickettsia prowazekii has been followed in L-929 cells 4 days post-infection (p.i.) by cryoultramicrotomy. Groups of rickettsiae were present in the cytoplasm outside of vacuoles forming microcolonies. The size of rickettsiae amounted to 400 X 700 nm, the average thickness of the cell wall was 5 nm, that of periplasmic space and cytoplasmic membrane 14 and 6 nm, respectively. Within intracytoplasmic colonies the rickettsiae were tightly packed and their cell walls were closely adjacent to each other. No halo or capsule-like coating around them was detected. No ultrastructural details were observed in the light translucent spaces between cells. Marginal rickettsiae of the microcolonies were often in close contact with the host cell mitochondria. PMID- 2878590 TI - Oligonucleotide fingerprint analysis on Japanese encephalitis virus strains after passage histories. AB - Genetic variation in Japanese encephalitis (JE) virus strains after various passage histories was examined by oligonucleotide fingerprints of the 42S genome RNA. The results indicated that genome changes occurred during passages of new virus isolates through cell lines or mouse brains, especially at earlier passage level in order to adapt quickly to different hosts. However, the changes were not sufficient to explain strain differences observed among fingerprints of various isolates. PMID- 2878592 TI - Some physical and chemical properties of Bhanja virus. AB - Bhanja virus is acid-labile, relatively thermostable, resistant to trypsin and heparin; a complete inactivation was achieved with chloramine B or formaldehyde, while phenol was ineffective, and UV radiation only partially effective. PMID- 2878593 TI - Isolation of enteroviruses from water. PMID- 2878594 TI - A symposium: Bevantolol--a new cardiovascular agent with a unique profile. April 21, 1985, Geneva, Switzerland. PMID- 2878595 TI - Once- and twice-daily bevantolol for systemic hypertension using 24-hour ambulatory intraarterial blood pressure recording. AB - The antihypertensive efficacy of bevantolol, a selective beta 1-adrenoreceptor antagonist, was evaluated in 17 patients with essential hypertension, using continuous ambulatory intraarterial blood pressure (BP) monitoring. The study compared a twice-daily regimen (titrated dose of 200 to 600 mg/day) with the same amount given in a single daily dose. Within-patient comparisons of mean hourly systolic and diastolic BPs and heart rate showed a highly significant effect with twice-daily therapy (p less than 0.001) for all of the 24 hours. Similar significant results were obtained with a single morning dose. There was no difference between the pattern or extent of BP reduction with the 2 regimens. The decrease in BP after bevantolol persisted during the physiologic tests (rest, tilt, isometric and dynamic exercise). Four patients developed minor side effects with the single morning dose, and only 1 patient with the twice-daily regimen. These effects included tiredness, fatigue and dizziness. Unlike pure beta blocking agents, bevantolol controlled the early morning increase in BP, lending support to the belief that it possesses vasodilatory properties in addition to beta blockade. These results suggest that bevantolol may be useful as first-line therapy in a once-daily dosage for the treatment of essential hypertension. PMID- 2878596 TI - Renal hemodynamics and pharmacokinetics of bevantolol in patients with impaired renal function. AB - The effects of bevantolol on renal blood flow and glomerular filtration rate and the drug's pharmacokinetics were studied for 7 days in 18 patients (mean age 50 years) with varying degrees of renal dysfunction. Patients were divided into 3 groups: group 1 had a creatinine clearance of 50 to 80 ml/min, group 2, 20 to 49 ml/min and group 3, less than 20 ml/min. After baseline inulin and paraaminohippuric acid clearance values were obtained, patients were given a single, 150-mg "priming" administration of bevantolol. The kinetics of the drug (including plasma drug levels, plasma half-life and plasma clearance) and its effects on renal function were observed for 24 hours. On days 4 to 6 of the study, patients received 150 mg of bevantolol twice daily, with only a single dose given on day 7. Bevantolol did not significantly affect either inulin or paraaminohippuric acid clearance in patients with differing degrees of renal function. In 50% of patients with a creatinine clearance of less than or equal to 50 ml/min, both the half-life and maximum trough serum levels were higher than the ranges seen in healthy subjects. However, neither value appears to be clinically relevant because bevantolol has a wide therapeutic range. Renal impairment did not change the percentages of the bevantolol dosage excreted unchanged or as conjugated drug in the urine, and no toxic or active drug metabolites accumulated in the blood. From these results, it appears that bevantolol may be used safely in short-term therapy of patients with renal impairment. PMID- 2878597 TI - Comparison of bevantolol and atenolol for systemic hypertension. AB - In an international, randomized, double-blind trial involving 229 patients, 400 mg of bevantolol was compared with 100 mg of atenolol (both in single daily doses) in the management of mild to moderate hypertension (diastolic blood pressure [BP] 95 to 115 mm Hg after a 4-week placebo washout period). Patients were then randomized to 12 weeks of treatment with either drug. Patients were evaluated at 2, 4, 8 and 12 weeks during the drug treatment period. Efficacy measurements were based on sitting and standing BP and heart rate. Adverse experiences were recorded on patient checklists, by spontaneous complaints and by 12-lead electrocardiography and funduscopy. A subgroup of 104 patients had heart rate and BP determinations every 24 to 26 hours after drug ingestion. Overall results showed both drugs to be comparably effective; no real difference was shown after 12 weeks of treatment. Bevantolol caused a more gradual BP decrease than atenolol. Both regimens were associated with decreased heart rate (less marked with bevantolol, p less than 0.001). Data from the 24-hour assessment subgroup showed similar results for both drugs, with a somewhat lower decrease in BP for bevantolol, which persisted throughout the study. Both drugs lowered sitting BP; the decrease was significantly less with bevantolol after the second week of therapy. The mean number of adverse experiences was similar for both drugs; cardiovascular side effects were less frequent with bevantolol. Patients taking bevantolol showed a higher incidence of digestive system side effects. Bevantolol maintained a 24-hour antihypertensive effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878598 TI - Usefulness of bevantolol for chronic, stable angina pectoris. AB - An objective assessment of the efficacy of bevantolol was performed in 21 patients with chronic, stable angina using computer-assisted exercise testing and ambulatory ST-segment monitoring. Given once daily, 200 mg of bevantolol was compared with 200 mg of bevantolol given twice daily and with placebo, using a double-blind crossover technique. The mean exercise time with placebo was 7.4 +/- 0.6 minutes; this increased to 10.6 +/- 0.9 minutes (p less than 0.001) with once daily bevantolol and to 9.4 +/- 0.9 minutes (p less than 0.001) with twice-daily bevantolol. The mean heart rate at rest was 80 +/- 3 beats/min with placebo; it decreased to 63 +/- 2 beats/min (p less than 0.001) with once-daily bevantolol and to 66 +/- 2 beats/min (p less than 0.001) with twice-daily bevantolol. The maximum exercise heart rate of 118 +/- 6 beats/min with placebo was reduced to 99 +/- 4 beats/min (p less than 0.001) on once-daily and 101 +/- 4 beats/min (p less than 0.001) on twice-daily bevantolol. There was a corresponding decrease in the rate-pressure product. The corrected maximum ST-segment depression was reduced from 0.3 +/- 0.06 mm min-1 with placebo to 0.2 +/- 0.03 mm min-1 (p less than 0.02) with once-daily and 0.2 +/- 0.04 mm min-1 (p less than 0.05) with twice daily bevantolol. The mean hourly ambulatory heart rate was significantly reduced for 21 hours with once-daily and 22 hours with twice-daily bevantolol. The lowest mean minimum heart rate was 55 beats/min during twice-daily treatment. The mean number of episodes of ST depression over 24 hours in lead CM5 was decreased from 6.89 +/- 1.7 with placebo to 2.50 +/- 0.6 (p less than 0.001) with once-daily and to 3.72 +/- 1.3 (p less than 0.001) with twice-daily bevantolol. Three patients were withdrawn during the once-daily bevantolol regimen due to adverse experiences, and another patient was admitted for coronary artery bypass surgery after 25 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878599 TI - Pharmacology of bevantolol hydrochloride. AB - Bevantolol is a cardioselective, beta-adrenoreceptor antagonist, devoid of intrinsic beta sympathomimetic activity and with weak membrane-stabilizing and local anesthetic properties. The 3,4-dimethoxyphenylethylamino moiety, substituted on the side chain amine function, confers cardioselectivity, which has been confirmed by a number of experiments. In vitro, bevantolol demonstrated greater antagonism of atrial than tracheal responses to isoproterenol. In vivo, bevantolol preferentially inhibited isoproterenol-induced tachycardias in conscious and anesthetized dogs, compared with the nonselective agent propranolol. Conversely, its effect on blood pressure after isoproterenol was minimal compared with propranolol, reflecting its muted effect on beta 2 peripheral receptors. A functional difference between bevantolol and propranolol was demonstrated in histamine-challenged guinea pigs. Bevantolol had little effect on the antiasthmatic effect of isoproterenol, whereas propranolol blocked it totally. Bevantolol's lack of intrinsic sympathomimetic activity was demonstrated in normal and reserpinized dogs, where it was devoid of intrinsic sympathomimetic activity at doses up to 10 mg/kg. Similarly, intravenous doses of 10 mg/kg had to be administered before direct myocardial depression occurred in the reserpinized animals. Metabolite 3, which is excreted in trace amounts in human urine, demonstrates intrinsic sympathomimetic activity when administered in pharmacologic doses to dogs; however, any clinical relevance remains to be established. Several laboratories have demonstrated that bevantolol interacts at alpha-adrenergic sites. These data require further investigation. The dose related antihypertensive effect of bevantolol has been demonstrated in spontaneously hypertensive and 2 kidney, 1 clip renal hypertensive rats. Animal experiments also suggest that bevantolol may be useful in angina: It caused a favorable redistribution of blood flow in dogs in which the left circumflex artery had been stenosed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878600 TI - Effects of bevantolol and atenolol on symptoms, exercise tolerance and metabolic risk factors in angina pectoris. AB - To assess the effects of bevantolol on stable angina pectoris of effort and its impact on metabolic risk factors, a comparison study of this beta 1-blocking agent and atenolol was undertaken in 40 subjects (mean age 51 years). After a 4 week, single-blind, placebo washout period, 12 men and 8 women were randomized to receive 150 mg of bevantolol twice daily and 12 men and 8 women to treatment with 100 mg of atenolol once daily in a parallel, double-blind, 12-week treatment phase. Patients were assessed at weeks 2, 6 and 12 after bicycle exercise until angina or ST-segment depression greater than or equal to 0.15 mV appeared. Concentrations of cholesterol lipoproteins and 3 prostaglandin metabolites were determined. One patient receiving bevantolol was withdrawn from the study because of insufficient efficacy and 2 receiving atenolol were withdrawn because of side effects. After 2 weeks of therapy, significant decreases were seen in both groups in the number of angina attacks, mean sitting heart rate, systolic and diastolic blood pressure, mean maximum heart rate during exercise and mean double-product of systolic blood pressure and heart rate at the end of exercise. There was a trend toward significance in the increase of mean duration of exercise and total work performed with both agents, although these values were not statistically significant. Both high density lipoproteins and the ratio of high density lipoproteins to low density lipoproteins increased in the bevantolol group and decreased in the atenolol group. These changes were statistically significant at week 6.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878601 TI - Systemic and regional hemodynamic, antiarrhythmic and antiischemic effects of bevantolol in anesthetized pigs. AB - In doses of 0.5 to 3.0 mg/kg bevantolol caused dose-dependent decreases in cardiac output (10% to 35%), primarily due to negative chronotropic actions, as heart rate decreased by 10% to 25%. Stroke volume decreased after the highest dose (15%), due to a negative inotropic action (maximum left ventricular dP/dt decreased by 40%) and a mild vasoconstriction in systemic vascular beds. Decreases in perfusion of the heart, kidneys, liver, spleen, stomach, muscles and adrenals were similar to those in cardiac output. However, blood flow to the brain and small intestine was not significantly affected. Bevantolol (0.5 or 1.5 mg/kg IV) gave full protection against ventricular fibrillation during the first period (10 minutes) of proximal left anterior descending (LAD) coronary artery occlusion in the highest dose. After the third and last reperfusion period, 70% of these animals survived, while only 8% of the untreated and 15% of the animals treated with the lower dose survived. After permanent ligation of the LAD coronary artery at midpoint, bevantolol prevented ventricular fibrillation during the first phase of early ventricular arrhythmias but was unable to prevent it during the second phase of early arrhythmias. Administration of bevantolol (1.5 mg/kg) to animals in which the LAD coronary artery blood flow was reduced to 35% of baseline did not improve transmural myocardial blood flow to the ischemic zone. However, the drug caused a redistribution in favor of the endocardial layers. The changes in flow were accompanied by a narrowing of the arterial coronary venous differences in pH and pCO2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878602 TI - Coronary and systemic hemodynamic effects of intravenous nisoldipine. AB - Systemic and coronary hemodynamic effects of the new dihydropyridine calcium antagonist nisoldipine were studied over a 30-minute period in 12 patients with angina pectoris. Previously instituted beta-blocker therapy was continued. Nisoldipine was administered in an intravenous bolus of 6 micrograms/kg over 3 minutes. Heart rate increased as mean aortic pressure and systemic vascular resistance decreased in all patients. Cardiac output increased significantly, from 5.8 +/- 0.3 to 7.9 +/- 0.5 liters/min, 10 minutes after nisoldipine infusion. These trends were maintained over the 30-minute observation period. Coronary sinus blood flow increased from 103 +/- 11 to 139 +/- 13 ml/min immediately after nisoldipine, but had returned to the control level by 30 minutes, as had the reduction in coronary vascular resistance. Myocardial oxygen consumption and heart rate-systolic blood pressure product did not change significantly. Nisoldipine is a potent peripheral and coronary vasodilator free of major myocardial depressant effects after acute intravenous administration. The systemic vasodilatory effects appear to outlast the coronary effects over 30 minutes. PMID- 2878603 TI - Plasma branched-chain keto acids in burn patients. AB - Plasma branched-chain keto acids (BCKA) and glucose-alanine cycle-related substances were measured in venous and arterial blood following burn injury. It was found that the three BCKA diminished with a minimum on day 7 while pyruvate increased. Alanine and glutamate + glutamine also decreased but plasma branched chain amino acids (BCAA) did not vary. BCKA and gluconeogenic amino acids were liberated by peripheral tissues whereas BCAA were not. By analogy with the fate of alanine, a reduction in plasma BCKA associated with a high release by peripheral tissues might involve an increase in their hepatic metabolism. The BCKA would then give rise to ketone bodies used by the peripheral tissue. This step would complete the glucose-alanine cycle described by Cahill in hypercatabolic states where energy requirements are intense and similar to those found in burn injuries. PMID- 2878604 TI - Cancer chemotherapy-induced tubular nephrotoxicity evaluated by immunochemical determination of urinary adenosine deaminase binding protein. AB - The authors evaluated measurements of adenosine deaminase binding protein (ADB), a proximal renal tubular cell antigen, for detection of drug-induced tubular nephrotoxicity. Concentrations of ADB were determined immunochemically in serial urine specimens from 12 children who were receiving chemotherapy for malignant solid tumors. There was no indication of increased ADB excretion after administration of two nonnephrotoxic drugs, etoposide and doxorubicin, but in patients given the recognized nephrotoxins, cisplatin and methotrexate, or an investigational drug, ifosfamide, urinary concentrations of ADB increased greater than fivefold relative to baseline values. Increased ADB concentrations preceded cisplatin- or ifosfamide-induced elevations of serum creatinine. Results of the ADB assay correlated well with those obtained by enzymatic assays for N-acetyl beta-D-glucosaminidase and alanine aminopeptidase (r = 0.76 and 0.53; n = 142, P less than 0.001) and marginally with total proteinuria (r = 0.21; P less than 0.02). Hence, serial ADB measurements may be useful in screening investigational drugs for acute subclinical nephrotoxicity. PMID- 2878606 TI - Escalator injury in foreign countries. PMID- 2878605 TI - Acquired undescended testes. AB - Three cases of reascent of a previously unequivocally documented descended testis have been encountered. Chorionic gonadotropin treatment was initially attempted in each child and was successful in causing descent of the involved testis in one. The testes of the other two boys were successfully brought down surgically. Possible causes for testicular reascent are presented and the pertinent literature is reviewed. These cases illustrate the need for continued diligence and interval examination of the pediatric scrotum throughout childhood. PMID- 2878607 TI - Nizatidine: a new histamine receptor blocker in the treatment of active duodenal ulcers. AB - Forty-three patients with newly diagnosed duodenal ulcers were treated with a new histamine blocker, nizatidine, and with placebo. The incidence of complete endoscopic healing was 38, 74, and 82% in the nizatidine treated patients compared with 25, 37, and 50% in the placebo treated group after 2, 4, and 8 wk of treatment, respectively. Nizatidine was clearly more effective than placebo after 4 wk of treatment. The size of unhealed ulcers decreased more than 50% in 62, 50, and 50% in the nizatidine treated groups versus 27, 25, and 40% in the placebo treated groups after 2, 4, and 8 wk of treatment, respectively. The difference between the two was not statistically significant for any given period. There was a significant correlation between day pain relief and ulcer healing in both treatment groups. Nizatidine significantly improved day pain relief only after 8 wk of treatment (p less than 0.01). No patient developed any side effects as a result of nizatidine treatment, except that the serum creatinine level rose from 1.05 to 1.1 mg/100 ml but still remained within the normal accepted range. This study demonstrated that nizatidine at 150 mg po bid could be effectively used in the treatment of duodenal ulcer disease. PMID- 2878608 TI - Takayasu's arteritis and ulcerative colitis. AB - This report describes a case of Takayasu's disease and ulcerative colitis occurring simultaneously in a 35-yr-old Sri Lankan woman. It is suggested that these two diseases may be immunologically related and the possible pathogenic mechanisms by which these two disorders may be associated are discussed. PMID- 2878609 TI - A fine structure physical map of the short arm of chromosome 5. AB - A series of somatic cell hybrids that retain abnormal chromosomes 5 from 11 different persons with deletions or translocations involving 5p have been isolated. One hundred twenty DNA fragments isolated from a genomic library enriched for sequences from 5p were regionally localized by Southern blot analysis of the hybrid cell deletion mapping panel, including five DNA fragments that reveal restriction fragment length polymorphisms. The fine structure physical map of 5p together with the identification of additional polymorphic loci will facilitate the construction of a complete linkage map of this region. In addition, DNA fragments localized to a region near the 5p15.2-5p15.3 border, which appears to be the segment of 5p that is critical in producing the phenotype associated with the cri du chat syndrome when it is rendered hemizygous by deletion, will be useful in a molecular and DNA level analysis of this deletion syndrome. PMID- 2878611 TI - RFLP locus DXS42 is proximal to the locus for hypoxanthine phosphoribosyltransferase. PMID- 2878610 TI - Molecular basis for HbH disease in Italy: geographical distribution of deletional and nondeletional alpha-thalassemia haplotypes. AB - We have investigated the molecular basis for HbH disease in 16 patients from Sardinia, and central and southern Italy. We have shown that HbH disease is produced by the interaction of at least 10 different deletional or nondeletional alpha-thalassemia haplotypes, some of which have been already described in the Mediterranean area (--Med,-(alpha)20.5,-alpha 3.7 type I,-alpha 3.7 type II, alpha 2 NcoI alpha 1, alpha 2 HphI alpha 1). Among the new mutations found in the course of our study, there is a complete deletion of the zeta-alpha cluster and three nondeletional determinants (alpha alpha T), affecting to various extents alpha-globin gene expression. The different alpha-thalassemia haplotypes are not evenly distributed throughout the country. Two alpha 0 determinants [-(alpha)20.5 and the complete deletion of the zeta-alpha cluster] and four alpha + determinants (-alpha 3.7 type II, three nondeletional alpha alpha T mutations) are found exclusively in southern Italy. PMID- 2878613 TI - Pharmacologic management of obstructive lung disease. Current perspectives. AB - Pharmacotherapy of obstructive lung disease has improved both quantitatively and qualitatively in recent decades: quantitatively with improvements in adrenergic and methylxanthine drugs and qualitatively with the addition of new classes of drugs, such as steroids, cromolyn, and, most recently, anticholinergic agents. Management of airways disease is based upon several principles: near-normal airways function should be aimed for; long-term, systemic, moderate-to-high-dose corticosteroids should be avoided if at all possible; the judicious use of polypharmacy should be undertaken whenever necessary to provide effective treatment while minimizing drug side effects; and the therapeutic program for a given individual should be tailored to that patient's specific responses to various treatments. Available pharmacologic agents have varying efficacies and adverse effects. The various agents may be used in a number of combinations. PMID- 2878612 TI - Airway mucus membrane: effects of beta-adrenergic and anticholinergic stimulation. AB - Mucus hypersecretion and non-continuous clearance of tracheobronchial mucus contribute to airflow obstruction in several pulmonary disease entities. Bronchospasm, which is frequently associated with bronchial asthma, can present simultaneously with mucus transport abnormalities. Therapy designed to dilate airways may produce secondary effects, which are deleterious to effective transport of lung mucus. Sympathomimetic agents, such as beta-adrenergic agonists, reduce the tone of bronchial smooth muscle and enhance the flow of mucus within lung airways. Parasympatholytic agents also improve airflow in the lungs, but their effects at the mucus membrane of the airways may not be beneficial. Atropine, an anticholinergic agent, apparently has dose-dependent effects on human mucociliary function and, administered orally, can reduce large airway mucus transport. However, newer anticholinergic agents, such as ipratropium bromide, are effective bronchodilators and do not exhibit unfavorable effects on lung mucus transport in either subjects with normal mucus secretion or those with hypersecretory disease entities, such as bronchitis. In mildly symptomatic asthmatic patients, aerosolized ipratropium decreased airway obstruction without consistent positive or negative influence on lung mucociliary function. PMID- 2878615 TI - Clinical application of DNA analysis in a family with OTC deficiency. AB - We describe the clinical application of DNA restriction fragment analysis to the genetic evaluation of a family with a child deficient in ornithine transcarbamylase (OTC). The results of protein loading studies and the interpretation of the DNA haplotype profiles for the human OTC gene are reported. DNA restriction fragment analysis may be a reliable technique for the prenatal diagnosis of OTC deficiency and identification of obligate carriers of this gene. PMID- 2878614 TI - Cholinergic and neurogenic mechanisms in obstructive airways disease. AB - Although primary neural control of airway function is through parasympathetic pathways, more recent evidence indicates that there are important adrenergic and non-adrenergic, non-cholinergic neural mechanisms that may also influence respiratory function. The parasympathetic nervous system component includes neural receptors in the airways as well as afferent and efferent pathways that travel in the vagus nerves. Afferent vagal sensory receptors mediate the response to irritant or rapidly adapting receptor activation, Hering-Breuer, and the unmyelinated "C" fibers or "J" receptor pathways. The motor component of the parasympathetic nervous system has several important functions that regulate tone in normal system has several important functions that regulate tone in normal and obstructed airways. These pathways affect the following respiratory structures: bronchial smooth muscle; the mucociliary system; the larynx; and the nose. Finally, the parasympathetic nervous system may play a role in some species in the control of breathing and in the hyperpneic responses associated with airflow obstruction. In addition to cholinergic neural mechanisms, bronchomotor tone may also be influenced by adrenergic mechanisms and non-adrenergic, non-cholinergic neural pathways. Although there is minimal innervation of the airways by the sympathetic nervous system, there is ample evidence that beta-adrenoreceptors are present on bronchial smooth muscle. Beta-receptor stimulation not only relaxes airway smooth muscle, but also inhibits mediator release from mast cells in the airways and may alter vascular permeability. Alpha-adrenoreceptors are found in human airways and stimulation of these receptors causes bronchoconstriction. Although the importance of alpha-adrenoreceptors has been questioned, recent evidence suggests that alpha stimulation may play a role in cold air- and exercise-induced asthma. Finally, non-adrenergic, non-cholinergic nerves have been shown to cause relaxation of human airways in in vivo studies. There is increasing evidence that vasoactive intestinal peptide and peptide histidine methanol are the mediators of these responses. More recently, other neuropeptides (substance P, neurokinin A, and calcitonin gene-related peptide) have been localized in nerves in airways. These cause bronchoconstriction in vitro and may be released from afferent nerve terminals by an axon reflex. Although the precise role of these substances in controlling airway tone and bronchial secretions in humans is not fully understood, they may have important modulatory effects on the neural control of airway function. PMID- 2878616 TI - Metabolic myopathies. AB - Six glycogen storage diseases (resulting from deficiencies of acid maltase, phosphorylase, phosphofructokinase, phosphoglycerate kinase, phosphoglycerate mutase, and lactate dehydrogenase) and one mitochondrial myopathy (cytochrome c oxidase deficiency) are reviewed to illustrate: clinical heterogeneity, biochemical heterogeneity, evidence for tissue-specific and developmentally controlled isozymes, and molecular genetic studies. PMID- 2878617 TI - A molecular approach to genetic counseling in the X-linked muscular dystrophies. AB - New molecular developments in our understanding of Duchenne and Becker muscular dystrophies are affecting the practical approach to genetic counseling, carrier detection, and prenatal prediction for these disorders. A plan of an investigation combining DNA and conventional techniques is outlined that is suitable for centers not actively engaged in molecular genetics research, based on the detection of molecular deletions, the most efficient use of multiple DNA polymorphisms, and the integration of this data with creatine kinase and pedigree information. Such an approach now allows accurate carrier detection for most women at risk as well as an acceptable degree of accuracy in prenatal detection for a proportion of carrier women. PMID- 2878618 TI - Lipid metabolism in xanthomatous skin of hypercholesterolemic rabbits. AB - The authors studied xanthomatous skin in cholesterol-fed rabbits for changes in lipid content and in activities of enzymes regulating intracellular lipid content. After 80 days of hypercholesterolemic diet, xanthomas were widespread and changes in lipid metabolism were marked. In both tissue homogenates and cell membrane pellets, unesterified cholesterol and phospholipids increased 2-fold to 6-fold, and cholesteryl esters increased about 30-fold. Tissue triglycerides, however, decreased to half the levels found in control skin. Cholesterol esterification rates, measured by activity of acyl coenzyme A: cholesterol acyltransferase, increased moderately to markedly; hydrolase activity against 4 methylumbelliferyl oleate also increased at both acid and neutral pH, but hydrolase activity against cholesterol oleate increased only at acid pH. Thus, hypercholesterolemia caused striking increases in intracellular cholesterol esterification rates, increases in lipase activity at both neutral and acid pH, and increases in cholesteryl ester hydrolase activity at acid pH. Increases in cholesterol-esterifying activity uniformly exceeded increases in cholesteryl ester hydrolytic activity in congruence with net accumulation of cholesteryl ester. Skin xanthoma grade, however, had no consistent relation to the cholesterol esterification rates. Instead, the enzyme data suggested that marked abnormalities of lipid metabolism are diffusely distributed through dermal tissue as a precondition for the focal emergence of xanthomas. PMID- 2878619 TI - Somatostatin potentiation of insulin-induced glucose uptake in normal individuals. AB - The ability of somatostatin (SRIF) to enhance insulin-stimulated glucose uptake was evaluated during clamp studies in normal individuals and patients with non insulin-dependent diabetes mellitus (NIDDM). The results demonstrated that glucose uptake at insulin levels of approximately 100 microU/ml was significantly greater (P less than 0.001) in normal individuals in response to insulin plus SRIF as compared with insulin alone. In contrast, SRIF did not enhance insulin stimulated glucose uptake in patients with NIDDM. Measurements were also made of the relative ability of insulin as compared with insulin plus SRIF to suppress C peptide and glucagon concentrations during the clamp studies. The results of these experiments showed that SRIF did not potentiate the ability of insulin to suppress C-peptide concentrations in normal subjects but did in patients with NIDDM. However, plasma glucagon levels were reduced to a greater degree when SRIF was added to insulin in both normal and diabetic individuals. PMID- 2878620 TI - Mode of adrenergic and peptidergic inhibition of ion transport in flounder gill. AB - The mechanisms of inhibition of branchial ion transport by epinephrine and somatostatin were investigated in the isolated perfused gill preparation of seawater-adapted flounder Platichthys flesus. The electrogenic transepithelial potential recorded in gills perfused and bathed with identical salines was stimulated by glucagon, forskolin, or a cyclic adenosine 5' monophosphate (AMP) derivative, each administered at a concentration identified in preliminary experiments as being submaximally effective. The subsequent abilities of epinephrine and somatostatin to inhibit the stimulated potential were found to be dependent on the site of action of the stimulatory agent with respect to the formation of cyclic AMP. Thus the maximal adrenergic or peptidergic inhibition of the potential stimulated by exogenous cyclic AMP was significantly reduced compared with the maximal inhibition of the potential stimulated by either forskolin or glucagon. The data indicate dual modes of action by which epinephrine and somatostatin achieve maximal inhibition of branchial ion transport; a cyclic AMP-independent mechanism that is effective in the presence of cyclic AMP and an additional mechanism to inhibit cyclic AMP synthesis. PMID- 2878621 TI - Menstrual cycle and sensitivity of human fallopian tube to prostaglandins. AB - The shapes and frequencies of spontaneous contractions of circular muscle strips of the human oviduct differ during the menstrual cycles. However, under given conditions, the frequency and amplitude of the contractions were continuously reduced during perfusion with Krebs solution. In the presence of prostaglandin (PG) synthesis inhibitors or an antagonist, a gradual and continuous reduction was no longer observed, and low concentrations (10(-15)-10(-10) M) of PGE2 markedly suppressed the amplitude and frequency of the spontaneous contractions. The highest sensitivity of smooth muscle cells to PGE2 was observed during the periovulatory phases. Spontaneous prepotentials followed by slow waves were observed, and the latter potentials triggered contraction of the tissue. PGE2 (10(-14)-10(-12) M) inhibited, and PGF2 alpha (10(-9)-10(-7) M) enhanced the frequency of these slow waves. The amount of PGE series released from the tissues was twice of PGF series. These results suggest that endogenous prostaglandins play a physiological role in the transport of ovum in the human fallopian tube as a result of the regulation of spontaneous membrane and mechanical activities. PMID- 2878622 TI - Failure of buspirone to manage benzodiazepine withdrawal. AB - Fifteen patients with 146 cumulative years of tranquilizer use were withdrawn from their benzodiazepine (nine gradually and six abruptly), and buspirone, a new nonbenzodiazepine anxiolytic, was substituted. The addition of buspirone did not appear to lessen the intensity of the withdrawal state. This finding supports preclinical studies indicating that buspirone has no clinically significant benzodiazepine receptor activity. PMID- 2878624 TI - Do psychostimulants kindle panic disorder? PMID- 2878623 TI - Prevalence of misuse of prescribed benzodiazepines in patients with primary anxiety disorder or major depression. AB - Seventy-one patients with major depression or an anxiety disorder were treated with benzodiazepines. They were followed prospectively for evidence of misuse or abuse. There was no evidence of benzodiazepine abuse. Five patients (all with major depression) misused their benzodiazepines. PMID- 2878625 TI - Isoenzyme patterns of Entamoeba histolytica isolates from asymptomatic carriers: use of gradient acrylamide gels. AB - A vertical polyacrylamide gradient gel (3% to 7%) was designed to facilitate the electrophoretic resolution and classification of isoenzyme patterns of Entamoeba histolytica isolates. The following enzyme systems were used: phosphoglucomutase (PGM), hexokinase (HX), glucosephosphate isomerase (GPI), and malate dehydrogenase (ME). The modifications in the electrophoretic procedure and sample preparation allowed the reproducible comparison of enzyme patterns of axenic, monoxenic, and mixed cultures of E. histolytica isolated from humans. The clear distinction obtained in gradient polyacrylamide gels, between amebic isoenzyme bands and those from bacteria, renders this technique adequate for application to epidemiological studies where mixed cultures are used. The isoenzyme patterns of eight isolates from asymptomatic carriers, rigorously characterized by the absence of clinical, endoscopic, and serological findings were studied and compared with three well characterized pathogenic strains, cultured under axenic conditions. Our observations confirm the existence of distinct isoenzyme patterns for PGM, HX, and GPI in pathogenic and nonpathogenic strains, and reveal the consistent presence of more than one band for GPI. In addition, a previously undescribed band for GPI with an Rf of 0.64 in a carrier strain was found. The results suggest that while carriers usually harbor amebas with nonpathogenic isoenzyme patterns, pathogenic patterns also may be found in carriers. PMID- 2878627 TI - Experimental vertical transmission of Saint Louis encephalitis virus by Florida mosquitoes. AB - Vertical transmission of St. Louis encephalitis (SLE) virus to F1 larval progeny was demonstrated in 8 species of mosquitoes which occur in Florida: Culex quinquefasciatus, Cx. nigripalpus, Cx. salinarius, Cx. restuans, Cx. opisthopus, Anopheles quadrimaculatus, An. albimanus, and Aedes taeniorhynchus. Relatively high rates of such transmission were observed in Ae. taeniorhynchus and vertical transmission to F1 adult progeny and venereal transmission from males to females also were demonstrated with this species. Larval rearing temperature affected transstadial transmission of the virus in Ae. taeniorhynchus, especially to the adult stage. Such transmission was observed with a larval rearing temperature of 18 degrees C but not at 27 degrees C. Because of the abundance and distribution of Ae. taeniorhynchus in Florida, and the relatively high rates of vertical transmission of SLE virus observed in the present experiments, this mosquito species warrants further investigation as a possible overwintering host for the virus in that locality. PMID- 2878626 TI - Virus-vector-host relationships of Aedes stimulans and Jamestown Canyon virus in a northern Indiana enzootic focus. AB - Collections of hematophagous Diptera at the Kingsbury State Fish and Wildlife Area in northern Indiana between 1982 and 1984 yielded 118,972 mosquitoes from which 5 isolates of Jamestown Canyon virus and 3 isolates of trivittatus virus were obtained. All Jamestown Canyon isolates were from Aedes stimulans, including 1 from a pool of newly emerged males and 2 from pools of newly emerged females. These 3 isolates suggest that Jamestown Canyon virus is transovarially transmitted by Ae. stimulans. All isolates of trivittatus virus came from pools of Ae. trivittatus. No isolates were obtained from greater than 4,000 tabanids collected along with the mosquitoes those years. Transmission trials with field collected newly emerged adult female Ae. stimulans demonstrated a mean midgut infection rate of 44%, a disseminated infection rate of 16%, and an oral transmission rate of 12% to suckling mice. Precipitin tests of field-collected bloodfed female mosquitoes indicated that white-tailed deer were the preferred host for numerous mosquito species including Ae. stimulans. The results of this study suggest that Ae. stimulans is a primary vector of Jamestown Canyon virus and that transovarial transmission is the probable overwintering mechanism for this California group virus. PMID- 2878628 TI - [Endocrine cells in uterine tumors]. PMID- 2878629 TI - Testicular biopsy in children with leukemia and cryptorchidism: is confirmatory biopsy of undescended testis necessary? PMID- 2878630 TI - Potentiation of epidural opioids with epidural droperidol. A one year retrospective study. AB - During a period of one year, 119 patients with chronic pain received injections of opioids via a catheter inserted in the lumbar epidural space. Twenty-three patients (19%) showed evidence of tolerance and were given droperidol 1.25-5.0 mg epidurally. In 20 patients in this study, there was a significant reduction in the number of epidural opioid injections. Six patients complained of excessive sedation, which disappeared when the dose of droperidol was reduced, although this did not affect the analgesia. One patient given an accidental overdose of droperidol developed reversible Parkinsonism. It is concluded that epidural administration of the dopamine antagonist droperidol may be beneficial as supplementary medication to epidural opioids when tolerance develops. PMID- 2878631 TI - Recovery times following edrophonium and neostigmine reversal of pancuronium, atracurium, and vecuronium steady-state infusions. AB - The ability of edrophonium and neostigmine to antagonize nondepolarizing neuromuscular blockade produced by steady-state infusions of atracurium, pancuronium, and vecuronium was studied in 71 adult patients anesthetized with nitrous oxide and halothane. Infusion rates of blocking drugs were adjusted so that single twitch depression as measured by the evoked integrated EMG of the hypothenar muscles was kept at 10% of control. Two minutes after the termination of the infusion either edrophonium (0.75 mg/kg) or neostigmine (0.05 mg/kg) was administered. Single twitch depression and train-of-four (T4/T1) fade was recorded during the recovery period. T4/T1 fade ratios observed at 20 min postreversal were 0.80 (atracurium-edrophonium); 0.76 (vecuronium-edrophonium); 0.44 (pancuronium-edrophonium); 0.95 (atracurium-neostigmine); 0.89 (vecuronium neostigmine); and 0.68 (pancuronium-neostigmine). Under conditions of this study neostigmine produced more rapid and complete recovery than did edrophonium. Although edrophonium produced adequate antagonism of atracurium if 20-30 min were allowed to elapse, edrophonium reversal of pancuronium was rarely acceptable even at 30 min. Increasing the dose of edrophonium to 1.0 mg/kg produced single twitch values of 0.90 at 5 min postreversal but did not increase the rate of recovery of the train-of-four fade ratio. Neostigmine reversal of pancuronium, on the other hand, generally produced T4/T1 ratios of greater than 0.70 in 20-30 min. Although the pattern of recovery seen after reversal of vecuronium was in general quite similar to that seen after atracurium, two patients in the vecuronium-edrophonium group showed delayed recovery and also failed to respond significantly to subsequent doses of neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878632 TI - Effects of beta adrenergic receptor agonists and antagonists in diabetics with symptoms of postural hypotension: a double-blind, placebo-controlled study. AB - Eleven patients with hyperadrenergic diabetic postural hypotension and vagal neuropathy were treated in a double-blind, placebo-controlled study with different beta-agonists and antagonists. A single dose of the beta 2-agonist terbutaline (5 mg) and the beta 1 + 2-agonist orciprenaline (10 mg) did not reduce the fall in systolic pressure on standing up, despite a significant increase in both supine and standing heart rates. The beta 1-antagonist with intrinsic sympathicomimetic activity (ISA) acebutolol (200 mg) and the beta 1 antagonist metoprolol (50 mg) did not influence the fall in systolic pressure either, despite a significant decrease in supine and standing heart rates and disappearance of increase in heart rate on standing up. Only the beta 1 + 2 antagonist propranolol and the beta 1 + 2-antagonist with ISA pindolol (5 mg) could significantly reduce or practically abolish the fall in systolic and diastolic pressure on standing up. This was accompanied by a slight decrease of heart rates and disappearance of difference between supine and standing heart rates, as seen with the other beta-antagonists. Thus, only beta 2-blockade reduced or abolished the fall in systolic pressure on standing up in our patients. These data were confirmed by a three-week crossover trial in 10 of these patients. PMID- 2878633 TI - [Evaluation of enzyme modules of the Beckman Astra 8]. AB - We evaluated the analytical performances of the Beckman Astra 8 enzyme analyser which allows the determination of the 6 enzymes (creatine kinase, Aspartate aminotransferase, Alanine aminotransferase, gamma glutamyl-transferase, lactate dehydrogenase, Alcaline Phosphatases), in a same serum sample with only two modules. We compared the results obtained in the healthy and pathological subject's sera with those given by a centrifugal analyser IL Multistat III (Delhomme) using reagents and temperature recommended by SFBC (Societe Francaise de Biologie Clinique). Instrument utilization is greatly helped by various alarms and diagnostic programmes. Results for emergency and routine determinations accord with those announced by the manufacturer and those required for a modern enzymatic analyzer. PMID- 2878634 TI - Prevalence of K88, K99, and 987P pili of Escherichia coli in neonatal pigs with enteric colibacillosis. AB - One hundred nineteen live neonatal pigs with diarrhea less than or equal to 2 weeks old were euthanatized, and frozen sections of their ilea were submitted to an indirect fluorescent antibody technique to identify K88, K99, and 987P pili (also referred to as F-4, F-5, and F-6 pili, respectively) in Escherichia coli. Ten-centimeter ileal sections were used to determine numbers of lactose fermenting bacteria. Of 52 pigs in which E coli pili were found, 14 had K88 (27%), 23 had K99 (44%), 13 had 987P (25%), and 2 had K88 and K99 simultaneously (4%). Numbers of lactose-fermenting bacteria were significantly (P less than or equal to 0.05) higher in pigs with piliated E coli than in pigs without piliated E coli. Results of this study indicated that piliated E coli are a major cause of enteric disease in neonatal swine in Michigan, and that in pigs less than or equal to 2 weeks of age, K99 was the most frequently encountered pilus antigen. PMID- 2878635 TI - Increase of serum gamma-glutamyltransferase in neonatal Standardbred foals. AB - Serial blood samples were obtained from 16 Standardbred foals from time of birth to postpartum day 28. Sera were obtained and analyzed for gamma glutamyltransferase (GGT), aspartate transaminase, and immunoglobulin (Ig) G. Presuckle colostrum from the respective mares of these foals was analyzed for GGT activity. Mean serum aspartate transaminase activities were significantly increased above presuckle values by postpartum hour 48 (P less than 0.01) and increased gradually over the first 14 days. Mean serum IgG concentrations were significantly greater than presuckle values by 5 hours after foals first suckled (P less than 0.01) and remained significantly increased during the 28-day sampling period. Serum GGT activity did not differ significantly over the period sampled. The SD were large, since there was a large degree of interindividual variation. Serum GGT activity in the foals was significantly increased over that in the mares throughout the period of the study. The profile of serum GGT activity over time in each foal did not show a pattern of change. There was no postsuckle increase in serum GGT activity nor a correlation between serum GGT activities and IgG concentrations at 24 hours after foals first suckled. Evidence was not obtained to support a colostric source of GGT involved in the increase of serum GGT activity in foals. Serum GGT activity seems to be increased in foals due to endogenous sources. PMID- 2878636 TI - Effects of the calcium channel blocker, verapamil, on asthmatic airway responses to muscarinic, histaminergic, and allergenic stimuli. PMID- 2878637 TI - Molecular genetics and T cells in autoimmunity. PMID- 2878638 TI - Absence of antibody to HTLV I and III in sera of Canadian patients with multiple sclerosis and chronic myelopathy. AB - Recently, elevated titers of antibody to HTLV I have been demonstrated in patients with tropical spastic paraparesis and multiple sclerosis. We evaluated the possible role of human retroviruses HTLV I and III in Canadian patients with multiple sclerosis and chronic idiopathic myelopathy. Using sensitive enzyme immunoassays, we were unable to find antibody to either HTLV I or III in 201 patients with multiple sclerosis, 29 patients with chronic myelopathy, 51 patients with other neurological disorders, or 29 normal subjects. These data do not support a role for these viruses in the cause of sporadic multiple sclerosis and chronic myelopathy in a regionally based Canadian population, but do not exclude a role for other antigenically distinct retroviruses. PMID- 2878639 TI - A postmortem study of amino acid neurotransmitters in Alzheimer's disease. AB - Concentrations of putative neurotransmitter amino acids were measured in postmortem brains from 10 patients with Alzheimer's disease and 10 controls. Glutamate, aspartate, taurine, gamma-aminobutyric acid (GABA), and alanine levels were examined in 9 cortical regions, hippocampus, thalamus, and basal ganglia using high-performance liquid chromatography with electrochemical detection. There were no significant alterations in aspartate, taurine, or alanine levels in any of the regions examined. Widespread significant reductions in cortical GABA concentrations were observed in the Alzheimer's brains, with the largest decreases in the temporal lobe. Overall values for glutamate concentrations in temporal and frontal cortices showed a significant 12% reduction in Alzheimer's brains, but the only individual cortical region showing a significant reduction in glutamate was the inferior temporal gyrus. These results suggest that gamma aminobutyric acidergic neurons in Alzheimer's cerebral cortex may be selectively vulnerable to the disease process. PMID- 2878640 TI - [Electron microscopic study of the interaction of cultures of Bordetella pertussis altered by antibiotic action with a human amniotic cell culture]. AB - The adhesive properties of B. pertussis subjected to long-term subcultivation on nutrient media with antibiotics were studied with electron microscopy and it was shown that under the action of erythromycin the adhesive capacity of B. pertussis markedly decreased. Subcultivation on media with tetracycline did not lower the adhesive activity of B. pertussis. Changes in the adhesive properties of B. pertussis under the action of the antibiotics correlated with changes in toxicity, serovars and ultrastructure of the bacteria in the population. PMID- 2878641 TI - Effect of human milk folate binding protein on folate intestinal transport. AB - The present study examined the effect of human milk folate binding protein (FBP) on the intestinal transport of 5-methyltetrahydrofolate (5-CH3H4PteGlu). This was performed by examining the transport of radiolabeled 5-CH3H4PteGlu bound to FBP using everted sacs of rat intestine. In the jejunum at pH 6, transport of 27 nM bound 5-CH3H4PteGlu was linear with time for 30 min of incubation. Transport of 13 nM bound 5-CH3H4PteGlu was higher in the jejunum than in the ileum at both pH 6 (2.1 +/- 0.3 and 0.36 +/- 0.03 pmol/g wet wt/25 min, respectively) and pH 8 (1.9 +/- 0.3 and 0.32 +/- 0.02 pmol/g wet wt/25 min, respectively). In the jejunum, transport of 13 nM bound 5-CH3H4PteGlu at pH 6 was less than transport of an equimolar concentration of free 5-CH3H4PteGlu (2.1 +/- 0.3 and 5.1 +/- 0.5 pmol/g wet wt/25 min, respectively) but was similar at pH 8 (1.9 +/- 0.3 and 2.47 +/- 0.3 pmol/g wet wt/25 min, respectively). In the ileum transport of bound and free 5-CH3H4PteGlu was similar at pH 6 (0.36 +/- 0.03) and 0.41 +/- 0.06 pmol/g wet wt/25 min, respectively) and pH 8 (0.32 +/- 0.02 and 0.43 +/- 0.1 pmol/g wet wt/25 min, respectively). The transport process of bound 5-CH3H4PteGlu in the jejunum was energy, temperature, and Na+ dependent, but not pH dependent, and was competitively inhibited by sulfasalazine. Ninety-two percent of the transport substrate that appeared in the serosal compartment following incubation with bound 5-CH3H4PteGlu was found to be free (unbound) 5-CH3H4PteGlu. These results show that human milk FBP decreases the rate of transport of 5-CH3H4PteGlu in the jejunum and suggest that FBP-bound 5-CH3H4PteGlu may utilize the same transport system as free 5-CH3H4PteGlu. The results also suggest a role for human milk FBP in regulating the nutritional bioavailability of folate. PMID- 2878642 TI - [Human cancers and viruses]. AB - There is an increased amount of evidence to suggest that viruses play important roles in the development of certain types of human tumors. These include the hepatitis B virus in hepatocellular carcinoma, human papillomaviruses in cervical cancer, Epstein-Barr virus in Burkitt's lymphoma and nasopharyngeal carcinoma, and human T-lymphotrophic virus in adult T cell leukemia and hairy cell leukemia. These pieces of evidence have accumulated from both clinical and basic studies which have shown that these viruses are involved in some stage of the carcinogenic process. Because of the rapid development of techniques and knowledge of molecular biology, most of the gene structures of these viruses and their products have been identified. These results make it possible to understand more clearly the route of infection and have facilitated the production of vaccines, using DNA-recombinant techniques. A significant decrease in the incidence of these types of cancers is expected through prevention programs conducted throughout the general population against these viruses within 10 to 20 years. These virus-related human cancers also provide us with a good opportunity to understand the basic mechanisms involved in the development of human cancers in general. In the present paper, these points are stressed in addition to describing the recent progress made in the study on virus-related human cancers. PMID- 2878643 TI - The effect of carbaryl and malathion in combination on gamma-glutamyl transpeptidase and glutathione S-alkyltransferase activity in vitro. PMID- 2878644 TI - Serum and synovial fluid levels of angiotensin converting enzyme in polyarthritis. AB - Serum levels of angiotensin converting enzyme (ACE) activity in patients with rheumatoid arthritis (RA) (n = 48), osteoarthritis (OA) (n = 11), ankylosing spondylitis (n = 24), psoriatic arthritis (n = 12), and Behcet's syndrome (n = 20) were not significantly different from those of normal controls (n = 26). Synovial fluid ACE activity was lower in OA than in RA but was similar when corrected for protein levels. An increase in serum ACE concentration in patients with RA receiving captopril therapy is in agreement with previous results. There was some correlation of ACE with erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) but not with clinical indices in captopril treated patients. It is suggested that the beneficial actions of captopril in the treatment of RA are not due to its activity as an ACE inhibitor, but more probably a result of captopril being an aliphatic thiol. PMID- 2878646 TI - Sulphasalazine hepatotoxicity: lack of a hypersensitivity response. PMID- 2878647 TI - Longitudinal study of diarrhoeal disease in a peri-urban community in Manaus (Amazon-Brazil). AB - A 20-month longitudinal study of diarrhoeal disease was carried out in a poor peri-urban community of Manaus (Amazon-Brazil), and the attack rate of this disease ranged from 0.2 to 4.8 episodes of diarrhoea per person per year. The age group most affected was 0 to 35 months old. A probable aetiological agent was identified in 68 of the 110 faecal samples collected. The most frequent enteropathogens isolated were enterotoxigenic Escherichia coli and Giardia lamblia. Enterotoxigenic Escherichia coli was also isolated from stream-water and from flies collected inside a household. PMID- 2878645 TI - The abnormal cytotoxic T cell response to Epstein-Barr virus in rheumatoid arthritis is correlated with disease activity and occurs in other arthropathies. AB - The cytotoxic T cell response to Epstein-Barr virus as measured by the regression assay was found to be impaired in a group of patients with active rheumatoid arthritis (RA). When these patients responded clinically to treatment with sulphasalazine there was a concomitant increase in the strength of this virus specific T cell response. The suggestion of a correlation between disease activity and impairment in this immune response was borne out in studies of other groups of patients with RA. Thus six out of 10 hospitalised patients had abnormal regression compared with six out of 31 patients seen routinely as outpatients. Studies of patients with inflammatory arthropathies other than RA, however, also showed abnormal regression in four out of 16 patients. It is concluded that the impairment in the cytotoxic T cell response to Epstein-Barr virus in RA is influenced by disease activity, and that this abnormality is not a specific feature of rheumatoid disease. PMID- 2878648 TI - Fifteen years' experience with the internal mammary artery graft. AB - Initially, the internal mammary artery (IMA) was implanted into the myocardium, and 10 years later it was anastomosed directly to coronary arteries. Our experience with the IMA started with single attached grafts. To reduce injury to the pedicle and improve anastomotic accuracy, magnification, microsurgical techniques, and cardioplegia were introduced. After establishing excellent long term patency of the IMA and knowing of the high incidence of obstruction in saphenous vein grafts 7 to 10 years after operation, we hypothesized that multiple IMA coronary anastomoses could improve the long-term results of coronary artery bypass grafting. Bilateral IMA, sequential IMA, and IMA Y-grafts were used to increase the number of mammary coronary anastomoses to 3.1 per patient. Early clinical results and patency evaluations are encouraging. In our experience, the IMA has evolved from being implanted into the myocardium, to a single bypass graft to the left anterior descending coronary artery, and finally to being the bypass conduit of choice supplying blood to three or more obstructed coronary arteries or their branches. PMID- 2878649 TI - Selective inhibitory effect of the analog D5-F-TrP8-D-Cys14 somatostatin on the arginine induced release of insulin, growth hormone and glucagon, in normal human beings. PMID- 2878650 TI - Analogs of hypothalamic hormones. Present and future clinical applications. PMID- 2878651 TI - Electroencephalographic and behavioral changes produced by 5 beta progestins and its antagonism by 4-aminopyridine. PMID- 2878652 TI - [H2-antihistaminics. 31. 1,2,5-Triazine-2,4-diamines and -2,4,6-triamines with H2 antagonistic activity]. PMID- 2878654 TI - Effect of macular ablation on frequency and latency of motion-induced emesis in the squirrel monkey. AB - Three previously motion-emetic sensitive squirrel monkeys were rendered refractory to a standard motion-emetic regimen by a two-stage utriculosacculectomy procedure which preserved the cristae ampullares of semicircular canals. Three non-operated control squirrel monkeys tested on the same motion-emetic regimen time schedule as the operated animals remained motion emetic sensitive with regard to incidence, frequency, and latency of motion induced emetic responses. Following a sham surgical procedure (stapedectomy) performed on two of the latter animals and one additional new animal, the emetic incidence decreased from 100% to 89%, but the frequency and latency were not altered significantly. PMID- 2878653 TI - [Determination of phenazone distribution in the liver and spleen in the evaluation of the effect of alpha adrenergic blocking drugs in the rat]. PMID- 2878655 TI - Use of drugs in cardiac rehabilitation. PMID- 2878657 TI - Uncoupler titrations in co-reconstituted systems do not discriminate between localized and delocalized mechanisms of photo-phosphorylation. PMID- 2878658 TI - Possibilities and problems in genomic diagnosis of Duchenne muscular dystrophy with molecular probes. AB - Selected families affected with Duchenne muscular dystrophy from an extensive pedigree analysis with linked restriction fragment length polymorphisms and creatine kinase estimations are compiled to demonstrate the various counselling situations for carrier determination and prenatal diagnosis. The creatine kinase determination suffers from approximately 30% false negative values in carrier determination. The DNA analysis is limited by the uninformativity of the DNA markers and the occurrence of meiotic crossovers between the particular restriction fragment length polymorphism pattern and the Duchenne muscular dystrophy locus. The use of markers bridging the Duchenne muscular dystrophy locus, such as 754 and C7, is presently best suited for this purpose but is applicable to only a relatively small number of cases. The use of the physically closer probe, pERT 87, is much more informative althrough it too recombines with the Duchenne muscular dystrophy locus. DNA analysis allows prenatal diagnosis for unaffected boys from the restriction fragment length polymorphism pattern confined to the healthy grandpaternal X-chromosome in cases where the carrier status of the mother is established or in doubt. As in the case of carrier determination, crossover events and uninformativity of restriction fragment length polymorphisms limit the feasibility of this approach. PMID- 2878656 TI - Formation of hexose 6-phosphates from lactate + pyruvate + glutamate by a cell free system from rat liver. AB - A cell-free system prepared from rat liver containing cytosol and mitochondria as well as a number of cofactors and gluconeogenic intermediates at near physiological concentrations was shown to form hexose 6-phosphates linearly from lactate + pyruvate + glutamate at a rate of 0.82 +/- 0.05 mumol/min per g of liver (mean +/- S.E.M., n = 8, 37 degrees C). The indicated rates were measured between 20 min and 60 min incubation time, when the system was near steady state. Experiments with either [1-14C]lactate or [U-14C]glutamate revealed that the incorporation of radioactive label into hexose 6-phosphates was proportional to the utilization of lactate + pyruvate and of glutamate during incubation and that both served as gluconeogenic substrates at a ratio of about 2:1. When the [ATP]/[ADP] ratio was lowered from 60 to 19 by addition of ATPase, the rate of hexose 6-phosphate formation fell to one-third. This decrease in gluconeogenic flux was mainly due to a decreased flow through the phosphoglycerate kinase step. Hexose 6-phosphate formation could also be decreased by increasing the ratio [NADH]/[NAD+], either by addition of ethanol or by increasing the initial concentration of lactate + pyruvate at a fixed ratio of 10:1. The observed inhibition was linked to a limitation in the availability of oxaloacetate for the phosphoenolpyruvate carboxykinase reaction and to an increased formation of sn glycerol 3-phosphate. Finally, the rates of hexose 6-phosphate formation in incubations with cytosols from fed rats were only 50% of those observed with cytosols from animals starved for 48 h. One of the limiting steps was found to be the flow through the phosphoenolpyruvate carboxykinase step. PMID- 2878659 TI - [Alanine aminopeptidases from small intestinal mucosa of dogs, rabbits and trout. I. Characterization of the "protease forms"]. AB - Alanine aminopeptidases from the mucous membranes of the small intestines of dog, rabbit and trout were concentrated 200 fold in the case of dog and rabbit, and 15 fold in the case of trout. The enzymes were analyzed with respect to substrate specificity, effector behaviour, optimum pH value, Michaelis constants and molecular weight. The values obtained for these enzymes are not consistent in all points with those found for alanine aminopeptidases isolated from the mucous membrane of human jejunum and ileum. PMID- 2878660 TI - [Alanine aminopeptidase from small intestinal mucosa of dogs, rabbits and trout. II. Behaviour of "detergent forms"]. AB - Alanine aminopeptidases from the mucous membranes of the small intestines of dog, rabbit and trout were purified as detergent forms. The enzymes obtained were characterized with respect to substrate specificity, effector behaviour, Michaelis constants, molecular weight and temperature dependence. In comparison to data of the protease forms of the alanine aminopeptidases, differences could be demonstrated. PMID- 2878661 TI - Natural history of the retrovirus associated with a human leukemia. PMID- 2878664 TI - More on the homeobox. PMID- 2878663 TI - On the homeobox and its significance. PMID- 2878662 TI - Homeo box fever, extrapolation and developmental biology. PMID- 2878665 TI - Potentiation by reduced glutathione of adriamycin-stimulated lipid peroxidation in kidney microsomes. PMID- 2878666 TI - Synapsin I: a synaptic vesicle-associated neuronal phosphoprotein. PMID- 2878668 TI - High plasma protein binding as a parameter in the selection of betablockers for lactating women. PMID- 2878667 TI - Effect of five structurally diverse H2-receptor antagonists on drug metabolism. AB - Some H2-receptor antagonists can interact with the biotransformation of other drugs. This is due to their binding to cytochrome P-450. We tested the in vitro effects of 5 different H2-receptor antagonists cimetidine (C), oxmetidine (O), ranitidine (R), famotidine (F) and nizatidine (N) on arylhydrocarbon-hydroxylase, 7-ethoxycoumarin-O-deethylase and 7-ethoxy-resorufin-O-deethylase activity using liver microsomes from man as well as from untreated, phenobarbital and 3 methylcholanthrene treated rats. In addition their binding to human microsomal cytochrome P-450 was evaluated. The in vivo effects of these antagonists were investigated on the hepatic elimination of diazepam in healthy volunteers. In vitro O was found to be the most effective inhibitor of the enzyme activities studied. C showed a clear inhibitory effect only with rat liver microsomes whereas the remaining drugs were more than 10 times less potent. The binding affinities of these antagonists showed a similar tendency: the Ks-values for O, C and R were 0.2, 0.9 and 5.1 mM, respectively; for F and N no binding up to 4 mM could be observed. However, in man, only C inhibited the hepatic elimination of diazepam by about 45% while R, O, N and F did not affect the pharmacokinetics of diazepam. Thus, it could be concluded from our studies that one cannot extrapolate in vitro data of the inhibitory potency of H2-receptor antagonists in every case to human in vivo drug metabolism. PMID- 2878669 TI - Antisecretory effects of two new histamine H2-receptor antagonists. AB - N-(3-[3-(1-Piperidinylmethyl)phenoxy]propyl)acetoxyaceta mide hydrochloride (Hoe 760) and N-(3-[3-(1-piperidinylmethyl)phenoxy]propyl)glycolamine hydrochloride (Hoe 062) are highly specific H2-receptor antagonists. The compounds are equipotent after intragastrical or intravenous administration. The antagonists inhibited gastric acid secretion in the rat induced by all stimuli tested, carbachol, desglugastrin and histamine. In the Heidenhain pouch dog whose gastric acid secretion was stimulated by food or histamine the two receptor blockers proved to be 4-6 times more potent inhibitors than cimetidine. PMID- 2878670 TI - Neural basis of psychomotor stimulant and opiate reward: evidence suggesting the involvement of a common dopaminergic system. AB - Data are reviewed that suggest a common neural system may be involved in the rewarding properties of psychomotor stimulant and opiate drugs. This neural system corresponds to elements in the ventral tegmental dopamine system with cell bodies in the ventral tegmentum and axon terminals in the nucleus accumbens. Several lines of evidence have shown that psychomotor stimulant reward involves a drug action in the nucleus accumbens and that opiate reward involves a drug action in the ventral tegmentum. Activation of the ventral tegmental system at either synaptic element can produce reinforcement by an enhancement of dopaminergic neurotransmission in the nucleus accumbens. Although additional brain systems may be involved in the rewarding actions of these compounds, their ability to activate the ventral tegmental dopamine system appears to make an important contribution to their net reinforcing impact. PMID- 2878671 TI - Neurotransmitters, pathways and circuits as the neural substrates of self stimulation of the prefrontal cortex: facts and speculations. AB - Through a multidisciplinary approach considerable progress has been made in understanding the neural substrates of self-stimulation (SS) of the medial prefrontal cortex (MPC). Thus, neuroanatomical studies have revealed that intrinsic neurones in the MPC seem to be the central elements responsible for initiating and maintaining this phenomenon in this area of the brain. Complementary to this central finding are the electrophysiological and neurohistological data reviewed here, showing that neurones in the MPC are directly activated and have monosynaptic feed-back connections with neurones located in areas which also support SS. These findings have given rise to the hypothesis that several single feed-back pathways or single circuits exist between points of SS in the MPC and points of SS in other areas of the brain. This hypothesis implies that SS in a particular area would depend not only on the intrinsic local activity induced by the electrical stimulation but on the functional and specific activity of other nuclei in the brain. The fact that lesions of single circuits, which are apparently involved in SS of the MPC such as the medial prefrontal cortex-ventrotegmental area-medial prefrontal cortex and medial prefrontal cortex-n. dorsomedialis of the thalamus-medial prefrontal cortex, do not produce a permanent decrease of SS, together with the finding that transynaptic connections seem to exist between MPC and other areas of the brain, suggests further that a complex rather than several single independent circuits could be at the neural basis of SS of the MPC. If that were the case, then SS of the MPC would not only depend upon local and single feed-back activity but upon specific functional feed-back activity among the nuclei, which in turn have single feed-back connections with the MPC (see the concept of 'complex circuit' outlined in the section of Behavioural studies). On the basis of this hypothesis no permanent changes should be expected after lesions of single pathways since physiological and even anatomical compensation could be reached through the rest of the undamaged circuit. That terminals containing specific neurotransmitters exist in layers of the PC where electrodes for SS are located has been reviewed in this paper. Some of these neurotransmitters have been suggested to be part of the local substrates activated by SS.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2878672 TI - A neuropharmacological study of the periventricular neural substrate involved in flight. AB - This paper reviews results obtained in experiments concerning the neurochemical characteristics of the substrate involved in the control of flight reactions and the induction of aversive effects in the rat. These experiments investigated the behavioural effects produced by microinjecting into the periaqueductal grey matter (PAG) or the medial hypothalamus (MH) compounds known to interfere with the functioning of some neurotransmitter systems known to exist in these structures. The data obtained show that: the activity of the substrate involved in the production of flight reactions is tonically inhibited by the release of GABA (gamma-aminobutyric acid); the behavioural reactions produced by microinjecting GABA antagonists can be clearly distinguished, depending on whether such drugs were injected into the PAG or the MH, despite the fact that jumps were produced from either level; behavioural effects, comparable to some extent to those produced by microinjections of GABA antagonists, can be obtained by injecting drugs which act on non-GABAergic neurochemical substrates, namely opioidergic or cholinergic systems; and behavioural effects, comparable to those produced by injecting GABA antagonists into the PAG, can be obtained by injecting such drugs into various sites located in other parts of the tectum such as the inferior colliculus or adjacent structures. PMID- 2878673 TI - Flight induced by microinjection of D-tubocurarine or alpha-bungarotoxin into medial hypothalamus or periaqueductal gray matter: cholinergic or GABAergic mediation? AB - Microinjections of various doses (50-300 ng) of the nicotinic antagonist D tubocurarine (TUBO) into the rat's medial hypothalamus (MH) or dorsal periaqueductal gray (PAG) produced flight reactions characterized by jumps. Two different types of flight reactions were produced depending on whether the drug was injected into the MH or into the PAG. MH injections provoked an increase in both locomotor activity and rearing together with well-oriented jumps. PAG injections provoked either freezing reactions or running with explosive jumps, but no increase in rearing. In addition, the rat exhibited an asymmetry in responsiveness to tactile stimulation. These reactions also differed depending on whether the drug was injected into the dorsal or ventral PAG. Behavioral reactions similar to those produced by TUBO were also produced by microinjection of the GABA receptor antagonist bicuculline into the same brain sites. Among the 4 putative cholinergic antagonists tested under the same conditions only alpha bungarotoxin produced effects that were qualitatively similar to those induced by D-tubocurarine or bicuculline. Gallamine and hemicholinium produced tremor when injected into sites located near the ventricular system at either the MH or the PAG level, while vocalizations were only produced by PAG injections. Hexamethonium produced no marked effect. The hypothesis that flight reactions induced by D-tubocurarine or alpha-bungarotoxin do not result from their antinicotinic action but rather from a direct effect on GABAergic transmission is discussed. PMID- 2878674 TI - Detection of TSH-binding inhibiting immunoglobulins in patients with Graves' disease and non toxic goiter. AB - The test of TSH-binding inhibiting antibodies is proving to be very useful for diagnosis and prognosis of hyperthyroidism. The aim of this investigation was to detect, with radioreceptor assay system, the incidence of TSH-binding inhibiting immunoglobulins (TIBAb) in our people. Therefore were examined sera of 19 patients with Graves' hyperthyroidism (150 and 40, mean age 39.9 years, range 24 62) and 9 patients with non toxic goiter (70, 20 mean age 46.6 years, range 25 46) at the first assessment, during treatment along twelve months and after another four months at the end of drug management. 12/19 patients with Graves' syndrome were TIBAB positive (sensitivity 63%) before drug therapy. The prevalence of TIBAb in sera increased after therapy (14/19) but values at the end declined. Three patients (two with persistent high levels of TIBAb at the end of treatment) relapsed. TIBAb were negative in patients with non toxic goiter (and in all normal subjects). PMID- 2878675 TI - Early treatment of unstable angina in the coronary care unit: a randomised, double blind, placebo controlled comparison of recurrent ischaemia in patients treated with nifedipine or metoprolol or both. Report of The Holland Interuniversity Nifedipine/Metoprolol Trial (HINT) Research Group. AB - A multicentre, double blind, placebo controlled, randomised trial of nifedipine, metoprolol, and nifedipine and metoprolol combined was conducted in a group of 338 patients with unstable angina not pretreated with a beta blocker and of nifedipine in 177 patients pretreated with a beta blocker. The main outcome event was recurrent ischaemia or myocardial infarction within 48 hours. Trial medication effects were expressed as ratios of event rates relative to placebo. In patients not pretreated with a beta blocker the event rate ratios with associated 95% confidence intervals were 1.15 (0.83, 1.64) for nifedipine, 0.76 (0.49, 1.16) for metoprolol, and 0.80 (0.53, 1.19) for nifedipine and metoprolol combined. In patients already on a beta blocker the addition of nifedipine was beneficial (rate ratio 0.68 (0.47, 0.97). Equal numbers of patients developed myocardial infarction and reversible ischaemia. Most infarctions occurred early, within six hours of randomisation. In patients not already on a beta blocker the nifedipine rate ratio for infarction only was 1.51 (0.87, 2.74). These results suggest that in patients not on previous beta blockade metoprolol has a beneficial short term effect on unstable angina, that fixed combination with nifedipine provides no further gain, and that nifedipine may be detrimental. On the other hand, the addition of nifedipine to existing beta blockade when the patient's condition becomes unstable seems beneficial. PMID- 2878676 TI - Oral xamoterol in patients with sinoatrial disease. AB - Twelve patients with sinoatrial disease were assessed while on oral xamoterol (200 mg twice daily) and placebo by a double blind randomised, crossover trial that lasted four weeks. Nine of the patients had been referred for permanent pacing. Xamoterol produced favourable changes in the number of pauses and the mean heart rate in six patients. Another patient deteriorated on xamoterol. Six patients were started on long term xamoterol. Xamoterol produces short term electrocardiographic improvement in some, but not all, patients with symptomatic sinoatrial disease. PMID- 2878677 TI - Anaesthesia for heart transplantation. A retrospective study and review. AB - The anaesthetic records of 261 heart transplant recipients were reviewed. Data collected included demographic characteristics, physical status, results of preoperative cardiac catheterization studies, anaesthetics agents and incidences of complications which may have been related to anaesthetic management. Forty five patients received a volatile agent (methoxyflurane 31, enflurane 10, halothane 4) and 216 patients were anaesthetized with a high-dose narcotic technique (morphine 122, fentanyl 71, hydromorphone 14, meperidine 9). Hypotension and arrhythmias were correlated with use of volatile and narcotic anaesthetics, respectively. No mortality was associated with anaesthetic management. PMID- 2878678 TI - Pharmacodynamic and pharmacokinetic studies on bufuralol in man. AB - Observations were made in eight subjects who exercised before and at 1, 2, 4, 6, 8 and 24 h after the double-blind oral administration of placebo, bufuralol 7.5, 15, 30, 60 and 120 mg and propranolol 40 and 160 mg. The exercise heart rate remained constant after placebo. Bufuralol 7.5 mg and propranolol 40 mg reduced exercise heart rate up to 6 and 8 h respectively after dosing but bufuralol 15, 30, 60 and 120 mg and propranolol 160 mg were still active at 24 h. The lowest exercise heart rate occurred at 2 h after all active treatments. Bufuralol 60 and 120 mg produced similar reduction in exercise tachycardia as propranolol 40 mg but less than propranolol 160 mg. Plasma levels of bufuralol and its two major metabolites were measured. The peak plasma concentrations of bufuralol occurred at 1.5 h after 7.5 mg and at 2 h after the other doses of bufuralol. In six subjects the plasma elimination half-life of bufuralol was 2.61 +/- 0.18 h and in the other three subjects 4.85 +/- 0.35 h. There was a corresponding longer time to peak concentration and plasma elimination half-life of the two metabolites in these three subjects. These findings show that bufuralol is a potent beta adrenoceptor antagonist with partial agonist activity. It has a long duration of action and there is bimodal metabolism of the drug in man. PMID- 2878679 TI - The action of a dopamine (DA1) receptor agonist, fenoldopam in human vasculature in vivo and in vitro. AB - This study was designed to investigate dopaminergic mechanisms in human vasculature using the selective vascular dopamine receptor agonist fenoldopam in vivo and in vitro. In vivo, forearm blood flow was measured plethysmographically and in vitro isolated rings of human blood vessels from a variety of sites were used for tissue bath studies. Intra-arterial fenoldopam markedly increased forearm blood flow, this effect was antagonised by (R) sulpiride, a vascular dopamine (DA1) antagonist, but not by metoclopramide, a neuronal (DA2) antagonist, or by guanethidine, an adrenergic neurone blocking agent. In vitro, fenoldopam relaxed preconstricted human renal, mesenteric and lumbar arteries, but not saphenous vein in a concentration dependent manner. (RS) sulpiride and SCH 23390 competitively antagonised this effect. These studies demonstrate the presence of a vasodilatory vascular dopamine receptor in man both in vivo and in vitro. PMID- 2878681 TI - Atypical angiomatosis in polyarteritis nodosa. AB - Biopsies from an area of livedo reticularis and adjacent to a leg ulcer in a woman with polyarteritis nodosa showed florid angioendothelial proliferation simulating angiosarcoma. This angioproliferative reaction has not been described previously in polyarteritis nodosa. Its microscopic differentiation from angiosarcoma is important. PMID- 2878680 TI - A comparative study on the ventilatory and haemodynamic effects of xamoterol and atenolol in asthmatic patients. AB - The effects of single oral doses of atenolol 50 mg and xamoterol 200 mg (a recently developed partial beta 1-adrenoceptor agonist) on lung function, heart rate and blood pressure were investigated in 11 patients with asthma. Xamoterol caused a significant increase in heart rate and systolic blood pressure, which changes are consistent with the partial beta 1-adrenoceptor agonist activity of this drug. Atenolol induced a significant decrease in FEV1 and the forced vital capacity (FVC); there was a non-significant change in FEV1 and FVC after xamoterol. There was no significant difference between the effects of atenolol and xamoterol of FEV1 and FVC. Bronchospasm induced by atenolol 50 mg and xamoterol 200 mg was completely reversed by inhalation of the beta 2-adrenoceptor agonist terbutaline to a cumulative dose of 4.0 mg. PMID- 2878683 TI - Effect of light and calcium on cyclic GMP synthesis in rod outer segments of toad retina. AB - The rod outer segments of toad retina contain a guanylate cyclase activity of about 3 +/- 1 nmol of cGMP formed/min per mg protein. In darkness this value is largely independent of the Ca2+ concentration, although it is enhanced by light upon lowering the Ca2+ concentration from 10(-5) to 10(-8) M. The activating effect of light on cyclase at low Ca2+ concentrations is enlarged upon increasing the light intensity. With a flash of light bleaching 7 X 10(-2) percent of rhodopsin, cyclase activity increased by a factor of 30 when Ca2+ levels dropped from 10(-5) to 10(-8) M. In view of recent observations that shortly after a flash of light the calcium activity inside the photoreceptor cell decreases, it seems likely that Ca2+ plays a regulatory role on cGMP metabolism in visual excitation. PMID- 2878682 TI - Cold-labile hemolysin produced by limited proteolysis of theta-toxin from Clostridium perfringens. AB - A nicked toxin whose hemolytic activity is temperature dependent was obtained by limited proteolysis of theta-toxin (Mr 54,000) with subtilisin. The nicked toxin (C theta) is a complex of two fragments: the N-terminal fragment (Mr 15,000) with basic isoelectric point and the C-terminal fragment (Mr 39,000) with the single cysteinyl residue of the toxin whose reduced form is essential for the hemolytic activity. C theta hemolyzes erythrocytes only at temperatures above 25 degrees C, whereas the native toxin hemolyzes them even at 10 degrees C. At temperatures below 25 degrees C, C theta does not hemolyze them although it does bind to membrane cholesterol and although no distinct difference was observed between the secondary structure of C theta and that of native toxin. It was found that C theta binds to the cells only in a reversible manner at low temperature, while the native one binds irreversibly to the cells within 10 min, which explains the cold lability of C theta on hemolysis. The structural basis of the cold lability was discussed through comparison of C theta with another nicked derivative of theta-toxin that was also obtained. PMID- 2878684 TI - Mutation that affects pepN translation initiation in Escherichia coli. AB - Mutants altered in their expression of the hybrid pepN-lacZ gene have been selected for resistance to p-nitrophenyl-beta-D-thiogalactopyranoside (a bacteriostatic compound that enters the cells via lac permease). A unique mutation decreasing the level of pepN expression to 9% of that of the wild type has been studied in detail. This mutation controls in cis the expression of the pepN gene. The pepN region from a pepN-lacZ gene fusion has been cloned and sequenced. Comparison of the mutant and wild type sequences indicates that the mutation lies between the Shine-Dalgarno sequence (AGGT) and the initiation codon (AUG). This mutation is a T----C transition which might allow the formation of a stable secondary structure in the region of translation initiation thus decreasing the level of pepN expression. PMID- 2878685 TI - Nucleotide sequence of the Azospirillum brasilense Sp7 glutamine synthetase structural gene. AB - The complete nucleotide sequence of the glnA gene, encoding the glutamine synthetase subunit of Azospirillum brasilense Sp7, was established. This is the first Azospirillum gene sequenced. The gene encodes a 468 residue polypeptide of MW 51,917. The similarity coefficient (SAB) between the polypeptidic sequence of Azospirillum and Anabaena 7120, which is the only other glnA sequence available, is 58%. No significant homology with E. coli canonical and ntr promoters, or with the promoter region of the Anabaena glnA gene was found. When fused to an E. coli promoter, the gene could be translated in E. coli, despite a very biased codon usage and an atypical Shine-Dalgarno sequence. PMID- 2878686 TI - The tonoplast proton-translocating ATPase of higher plants as a third class of proton-pumps. AB - Taken together, all the data reported recently in the literature suggest that tonoplast ATPase belongs to a new class of proton pumps. To date, the most studied system is the proton-pumping ATPase from the tonoplast of Hevea latex. Its main characteristics are presented. It resembles the mitochondrial ATPase in its specificity, its substrate affinity, and its sensitivity to different inhibitors. However, for some aspects, it resembles the plasma membrane system in its response to other inhibitors tested (quercetin for example). It differs from both ATPases in its sensitivity to nitrate as well as by its molecular structure, i.e. a complex exhibiting a least 4 or 5 polypeptides. These results favor the existence of a third class of proton pumps, intermediate between the F1F0-class and the E1E2-class. PMID- 2878687 TI - Does a proton-pumping ATPase exist in the tonoplast? AB - In order to account for the accumulation of metabolites in plant vacuoles, the existence of a proton-pumping ATPase has been widely suggested in the literature. The demonstration of such a tonoplast-bound ATPase was merely based on the characterization of a nitrate-sensitive microsomal fraction. In some examples, this ATPase activity has been evidenced on vacuole preparations obtained under conditions which were criticized by Boller. The application of the reverse phase high-performance liquid chromatography method (RP-HPLC) to the simultaneous separation of adenine nucleotides, in the presence of tonoplast vesicles isolated from Catharanthus roseus, showed results not necessarily correlated with the ATPase hypothesis. Moreover, in light of the H+-quenching of quinacrine fluorescence observed during ATP hydrolysis by vacuoles or tonoplast vesicles, the existence of a proton-pumping ATPase may be questioned. PMID- 2878688 TI - The proton-pumps at the plasmalemma of Catharanthus roseus cells. AB - Cultured Catharanthus roseus cells exhibit transmembrane ferricyanide (FIC) reduction which is associated with a proton translocation and a decrease in the ATP content of the cells. The H+ efflux and the ATP consumption may be counteracted by vanadate, a specific inhibitor of the ATPase activity, and by Na2WO4 which prevents FIC reduction. From these data it is concluded that the redox chain could be coupled with ATP hydrolysis for electrogenic proton extrusion which may involve a redox control mechanism for the plasmamembrane ATPase. PMID- 2878689 TI - The acylphosphate present in chromaffin granule membrane preparations is not associated with the proton-pump. AB - Chromaffin granule membranes were incubated in the presence of low ATP concentrations, at low temperature. A phosphorylated compound was rapidly formed which was stable in 10% trichloroacetic acid at 0 degree C. The lability of this compound in the presence of hydroxylamine or hot trichloroacetic acid indicated an acylphosphate, i.e., an ATPase phosphointermediate. Vanadate but not N ethylmaleimide inhibited the formation of this derivative. Since the ATP dependent generation of a transmembrane potential in chromaffin granule vesicles by the H+-pump was inhibited by N-ethylmaleimide but not by vanadate, the acylphosphate should not be associated with the H+-pump, i.e. ATPase I. We suggest that it is associated with ATPase II, an ATPase of unknown function present in chromaffin granule membrane preparations. This hypothesis is supported by the fact that ATPase II is vanadate sensitive and has a molecular mass of 140 kDa, properties similar to those of the phosphorylated intermediate. PMID- 2878690 TI - Remote and recent memory in long-hospitalized chronic schizophrenics. AB - This study shows that chronic, long-hospitalized schizophrenics perform (tested by the Famous Events Questionnaire) at a higher level on remote memory than they do on word list recall. A post hoc, matched-tasks check suggested that this finding was not due to differences in the discriminating power of the tasks. Relative to normals, patients showed no differential performance on the three time periods (1973/74, 1979/80, 1984) represented in the remote memory questionnaire, thus giving no evidence for an amnesic gradient. The findings are discussed in relation to amnesia and dementia hypotheses in chronic schizophrenia. PMID- 2878691 TI - Tranquillising memories: a review of the effects of benzodiazepines on human memory. AB - Studies from 1973 to 1985 of the effects of benzodiazepines on memory are summarised and reviewed. Anterograde amnesia appears a common effect of all benzodiazepines although its onset and duration vary with the particular benzodiazepine, its dose and route of administration. Memory impairments increase with task difficulty. There is some evidence that partial tolerance to amnesic effects develops with repeated doses of diazepam, but research with other benzodiazepines is inconclusive. Amnesia is in part a by-product of the sedative action of benzodiazepines, although these drugs may also have a specific effect of disrupting the consolidation of information in long-term memory. State dependent effects are partial and relatively small. Methodological problems are discussed and attention is drawn to the lack of repeated dose studies, of studies with patient populations and with anxious volunteers. PMID- 2878693 TI - Endometrial prostaglandin E2-binding sites in the pig: characterization and changes during the estrous cycle and early pregnancy. AB - Because prostaglandins (PGs) are thought to mediate, in part, endometrial responses at implantation in a number of species and because pig conceptuses are capable of producing PGs, we have characterized the binding of [3H]PGE2 to endometrium obtained from pigs during the estrous cycle and early pregnancy. Binding of [3H]PGE2 to a membrane preparation obtained from endometrium was temperature- and pH-dependent, and reversible. Pretreatment of the membrane preparation with proteolytic enzymes, phospholipase A2, or heat reduced subsequent specific binding of [3H]PGE2. PGE1 and PGE2 competed equally for binding, whereas relative cross-reactivity for other prostanoids and compounds tested was less than 5%. Scatchard analysis of specific binding suggested that two classes of binding sites were present, a high-affinity binding site with an apparent dissociation constant (Kd) of approximately equal to 6 pM, and a lower affinity site with an apparent Kd of approximately equal to 3 nM. For the high affinity binding site, estimates of apparent Kd did not differ between days of the estrous cycle, but maximum binding capacity did change, being lowest on Day 10 and highest on Days 0-5 of the cycle. For the lower-affinity binding site, estimates of the apparent Kd differed, being lowest on Day 10 and highest on Day 15; numbers of binding sites were lowest on Day 5 and highest on Day 15. Estimates of these variables on Day 15 of pregnancy did not differ significantly from Day 15 of the cycle. These data are consistent with the presence of PGE receptors within the endometrium of the pig. PMID- 2878692 TI - Separate neural systems mediate the steroid-dependent and steroid-independent suppression of tonic luteinizing hormone secretion in the anestrous ewe. AB - In the ewe, two types of seasonal fluctuations in secretion of tonic luteinizing hormone (LH) have been described: a steroid-dependent change whereby estradiol gains the capacity to suppress LH pulse frequency in anestrus, and a steroid independent decrease in pulse frequency in ovariectomized animals during anestrus. We have proposed that the former reflects activation, in anestrus, of estradiol-sensitive catecholaminergic neurons that inhibit gonadotropin-releasing hormone (GnRH). Three results reported here support this hypothesis: dopaminergic (pimozide) and alpha-adrenergic (phenoxybenzamine) antagonists increased LH in intact anestrous ewes without altering pituitary responses to GnRH; other dopaminergic (fluphenazine) and alpha-adrenergic (dibenamine) antagonists also increased LH in anestrus; agonists for dopaminergic (apomorphine) and alpha adrenergic (clonidine) receptors suppressed LH secretion in both seasons, suggesting that the appropriate receptors are present in breeding-season ewes. In contrast, catecholamines do not appear to mediate the steroid-independent suppression of pulse frequency; neither pimozide nor phenoxybenzamine increased LH pulse frequency in ovariectomized ewes during anestrus. When antagonists for 6 other neurotransmitter receptors (muscarinic and nicotinic cholinergic, GABAnergic, serotonergic, opioid, and beta-adrenergic) were tested in anestrus, only cyproheptadine, the serotonergic antagonist, increased pulse frequency in ovariectomized ewes. Cyproheptadine had no effect on frequency during the breeding season. On the basis of these results, we propose that the steroid dependent and -independent actions of anestrous photoperiod occur via catecholaminergic and serotonergic neurons, respectively. PMID- 2878694 TI - A role for guanine ribonucleotides in the regulation of myeloid cell maturation. AB - We have shown previously that induced maturation of the human myeloid leukemia cell line, HL-60, is associated with a selective down-regulation of guanine ribonucleotide synthesis and depletion of intracellular guanosine triphosphate (GTP) and guanosine diphosphate (GDP) pools. We showed, furthermore, that inhibitors of the enzyme, inosine monophosphate (IMP) dehydrogenase, which catalyzes the initial rate-limiting step of guanylate synthesis from the central intermediate IMP, are potent inducers of myeloid maturation in these cells. We now show that induced maturation of HL-60 cells is prevented or impaired if intracellular concentrations of guanine ribonucleotides are maintained at high levels. HL-60 cells can utilize exogenous guanine and guanosine to maintain GTP and GDP pools through a salvage pathway that bypasses guanylate synthesis from IMP. Moreover, incubation of HL-60 cells with guanosine or guanine (10(-6) to 10( 4) mol/L) prevents both the depletion of intracellular guanine ribonucleotides and the induction of myeloid maturation caused by the IMP dehydrogenase inhibitor, tiazofurin. These findings provide strong additional support for the concept that terminal myeloid differentiation is influenced by a guanine ribonucleotide-dependent regulatory system. PMID- 2878695 TI - Possible absence of common polymorphisms in coagulation factor IX gene in Japanese subjects. AB - Four distinct intragenic polymorphisms in the coagulation factor IX gene which have been reported to be important for family diagnosis of Caucasian hemophilia B were studied in 51 normal Japanese subjects (21 males and 30 females). High molecular-weight DNA prepared from peripheral blood lymphocytes were digested with endonuclease, Ddel, Mspl, Taql or Xmnl, and were studied by Southern blot analysis with factor IX complementary DNA as a probe. None of the minor fragments produced by these enzymes was found in the normal Japanese DNA samples tested, although the probe detects minor allelic forms in control Caucasian DNA samples. Our data suggest that the frequent polymorphic sites found in Caucasians are possibly absent in the Japanese population. PMID- 2878696 TI - High sensitivity assay for the alpha 2 antagonist 6-chloro-3-methyl-2,3,4,5 tetrahydro-1H-3-benzazepine and its desmethyl metabolite in plasma using gas chromatography mass spectrometry with ammonia/CCl4 chemical ionization. AB - A rapid and highly sensitive assay for quantifying the alpha 2-adrenoceptor antagonist SK&F 86466 and a desmethyl metabolite has been developed, using capillary column gas chromatography/chemical ionization mass spectrometry. This assay uses deuterium-labeled analogs of the analytes as internal standards, and has a lower limit of quantification of 100 pg ml-1. A novel reagent gas, consisting of carbon tetrachloride in anhydrous ammonia, was used to achieve maximal sensitivity. PMID- 2878697 TI - Medical treatment of pregnancy hypertension. AB - Hypertension is the single commonest cause of maternal mortality, but prompt and effective treatment with a variety of drugs, some more familiar than others, can reduce the risk of both maternal and fetal death. PMID- 2878698 TI - Analgesia for children. PMID- 2878699 TI - Subcortical dementia. Neuropsychology, neuropsychiatry, and pathophysiology. AB - Subcortical dementia refers to a clinical syndrome characterised by slowing of cognition, memory disturbances, difficulty with complex intellectual tasks such as strategy generation and problem solving, visuospatial abnormalities, and disturbances of mood and affect. The syndrome was first described by Kinnier Wilson, but further progress in development of the concept has occurred only within the past ten years. Subcortical dementia occurs in degenerative extrapyramidal disorders and has also been identified in inflammatory, infectious, and vascular conditions. Histologic, metabolic, and neurochemical investigations implicate dysfunction primarily of subcortical neurotransmitter systems and subcortical structures or subcortical-frontal connections in the genesis of the syndrome. Subcortical dementia contrasts neuropsychologically and anatomically with disorders such as dementia of the Alzheimer type that affect primarily the cerebral cortex. The clinical characteristics of subcortical dementia reflect the interruption of fundamental functions (motivation, mood, timing, arousal) mediated by phylogenetically and ontogenetically early maturing structures. PMID- 2878700 TI - Interactions between procyclidine and neuroleptic drugs. Some pharmacological and clinical aspects. AB - Procyclidine was administered to 25 chronic psychotic inpatients, stabilised on chlorpromazine, haloperidol or fluphenazine decanoate injection. We observed a significant reduction in mean serum levels of all three neuroleptic drugs which was reversed on stopping procyclidine and was inversely correlated with mean serum procyclidine levels. No significant alterations occurred on the BPRS scores or in serum prolactin levels throughout the study in any of the three groups. Possible mechanisms of this interaction and its clinical relevance are discussed. PMID- 2878701 TI - A case of resistant schizophrenia. AB - In an era when it is generally believed that the acute symptoms of schizophrenia can be controlled pharmacologically, the case of a young man who has remained almost continuously floridly psychotic for 13 years, despite treatment, is disquieting. Conventional psychiatric treatment appears to be rendered impotent. It is in this context that it may be of interest to report a summary of the proceedings of a Special Problems Conference held at the Institute of Psychiatry on 18 February 1985 to discuss such a case. PMID- 2878702 TI - Peripheral gangrene associated with beta-blockade. PMID- 2878703 TI - Syrup of ipecacuanha: is it really useful? PMID- 2878704 TI - Glucose tolerance during long term treatment with a somatostatin analogue. AB - Seven patients with active acromegaly were treated with SMS 201-995, an analogue of somatostatin, for one year, the maximum dose being 100 micrograms three times a day. Three patients had impaired glucose tolerance before treatment, due to insulin resistance in two and insulin deficiency in one. In all patients treatment with the analogue slightly increased postprandial glucose concentrations and suppressed insulin concentrations for two to two and a half hours after each injection; growth hormone concentrations decreased progressively with treatment. The patient with impaired glucose tolerance due to insulin deficiency developed diabetes mellitus after four months' treatment; concomitant treatment with glibenclamide resulted in a decreased glucose concentration and increased insulin concentration. This analogue of somatostatin had only minor side effects on glucose tolerance in patients with acromegaly and may be used in patients with impaired glucose tolerance provided that glucose concentrations are monitored closely. PMID- 2878706 TI - Messenger RNA from insect nervous tissue induces expression of neuronal acetylcholine receptors in Xenopus oocytes. AB - mRNA isolated from the nervous tissue of young insects microinjected in Xenopus oocytes induced the expression of alpha-toxin binding sites which were inserted into the surface membrane. Immunoprecipitation experiments revealed that the coded receptor polypeptides were processed to the authentic size, and ion flux studies demonstrated that functional nicotinic acetylcholine receptors were produced and inserted into the oocyte membrane. PMID- 2878705 TI - Application of a closely linked polymorphism of restriction fragment length to counselling and prenatal testing in families with myotonic dystrophy. AB - The close genetic linkage between the loci for apolipoprotein CII (ApoC2) and myotonic dystrophy makes ApoC2 the closest fully validated marker for prediction of myotonic dystrophy. Application to genetic counselling and presymptomatic and prenatal prediction is reported in seven families with myotonic dystrophy, including one case in which the disorder was excluded prenatally. Only one of the families did not have members with ApoC2 genotypes that allowed prediction, but careful clinical study of older family members was found to be an important factor. ApoC2 typing of families with myotonic dystrophy should be of practical help both in prediction for asymptomatic relatives and for prenatal diagnosis in pregnancies of an affected parent. PMID- 2878707 TI - Estrogen induction of sexual behavior in female rats and synthesis of polyadenylated messenger RNA in the ventromedial nucleus of the hypothalamus. AB - To test the hypothesis that estrogen stimulates sexual behavior by inducing transcription of polyadenylated messenger RNA, we studied the effects of cordycepin, an adenosine analog that disrupts polyadenylation, on the lordotic responses of ovariectomized female rats made sexually receptive with systemic injections of estradiol benzoate (EB) and progesterone (P). Cordycepin inhibited lordosis when infused into the ventromedial nucleus of the hypothalamus within an hour before the females received EB; its effectiveness varied linearly with dose. It did not significantly alter sexual behavior when infused into the medial preoptic area. A dose of cordycepin that decreased lordosis when infused 1 h before injection of 0.5 microgram EB did not affect the behavior when infused 1 h before injection of 500 micrograms P. Cordycepin does not suppress behavior by blocking estrogen uptake since it did not alter estrogen accumulation by hypothalamic cell nuclei. Cordycepin inhibits ribosomal RNA (rRNA) synthesis as well as polyadenylation. While this probably contributes to cordycepin's inhibitory effects on lordosis, it cannot fully account for them since a cytidine analog that inhibits rRNA synthesis without inhibiting polyadenylation did not mimic cordycepin's behavioral effects. Cordycepin may suppress synthesis of P receptors; however, this could not fully account for its behavioral effects since cordycepin also inhibited lordosis when the P receptor was bypassed by substituting methysergide for P. As assessed by protein synthesis autoradiography, cordycepin's effects are highly localized. The data support the notion that estrogen facilitates female sexual behavior by altering gene expression in the brain. PMID- 2878710 TI - Differences between the effects of noradrenaline and the beta-adrenoceptor agonist BRL 28410 in brown adipose tissue and hind limb of the anaesthetized rat. AB - In mature (450-600 g) 21 degrees C-acclimated male rats, anaesthetized with urethane, blood flow (measured by the radioactive microsphere technique) to brown adipose tissue (BAT) was determined during the infusion of the beta-adrenoceptor agonist BRL 28410 or noradrenaline bitartrate at doses chosen to give similar increases in whole body oxygen uptake. Blood flow to BAT during BRL 28410 infusion was only about one third of that found during noradrenaline infusion although increases in whole body thermogenesis were similar (55 and 77% for BRL 28410 and noradrenaline, respectively). This suggests that BAT may be less involved in the thermogenic response to BRL 28410 than to noradrenaline. In a separate experiment using slightly smaller rats (350-500 g) hind limb oxygen uptake was measured in situ using a venous bypass preparation. BRL 28410, at a dose having a maximum effect on whole body thermogenesis (53% increase), had no effect on oxygen delivery to the hind limb but significantly increased oxygen extraction by 33% (p less than 0.001). In contrast, noradrenaline, also at a dose that maximally increased whole body thermogenesis, led to a 35% decrease in oxygen delivery to the hind limb and no change in oxygen extraction. For the thermogenic beta-agonist BRL 28410 the hind limb, and presumably muscular tissue in general, may be contributing to thermogenesis. PMID- 2878708 TI - Presynaptic inhibitory effects of sotalol, propranolol, and acebutolol on noradrenaline release upon cardiac sympathetic nerve stimulation in anesthetized dogs. AB - Effect of sotalol (STL) was compared with that of (+/-)-propranolol, (+) propranolol (PPL), and acebutolol (ABL) on noradrenaline (NA) release as measured in coronary sinus (CS) blood during postganglionic stimulation (2 Hz, 30 s) of the left cardiac sympathetic nerves in anesthetized dogs. In control dogs receiving saline, increasing responses of CS-NA concentration, mean CS blood flow, and CS-NA output to repetitive stimulation were relatively stable throughout a given experimental period. Both STL (1,2.5, and 5 mg/kg, i.v.) and (+/-)-PPL (0.5 and 2.5 mg/kg, i.v.) diminished the increased CS-NA concentration by approximately 35 (P less than 0.05) to 60% (P less than 0.01) in a dose dependent fashion. However, (+)-PPL (0.02-2.5 mg/kg, i.v.) and ABL (0.5-5 mg/kg, i.v.) did not significantly alter the increasing response of CS-NA concentration upon stimulation. STL, (+/-)-PPL, and ABL markedly inhibited the CS blood flow response to stimulation at all doses tested, while (+)-PPL did not significantly diminish the flow response even at the highest dose tested. Consequently, CS-NA output decreased significantly (p less than 0.01) in the presence of STL, (+/-) PPL, and ABL at all doses tested but not with (+)-PPL at any dose tested. The inhibitory effect of STL and (+/-)-PPL on the increasing response of CS-NA concentration upon stimulation could be related to their beta-blocking effect, which exerts presumably on postulated presynaptic beta-adrenoceptors, as (+)-PPL did not at all diminish the response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878709 TI - Role of beta 2-adrenoceptors in the biological effect of autoimmune orchitis spleen cells. AB - Autoimmune orchitis induced an increment in beta 2-adrenoceptor populations in intact mouse spleen lymphocytes. Normal and autoimmune lymphocytes incubated with soterenol increased the mechanical response of isolated atria. Autoimmune cells were more effective than normal cells in inducing this response. Soterenol or spleen cells alone did not modify the contractility at the concentration used. Inhibitors of beta 2-adrenoceptors of spleen cells completely blunted the reaction between soterenol and lymphocytes, while when atria were exposed to butoxamine, mechanical activity induced by soterenol plus lymphocytes was not affected. Cell-free supernatants of lymphocytes exposed to soterenol elicited the reaction in the same way as soterenol-treated lymphocytes. Direct contact of cells with the assay organ was not necessary. Inhibitors of cyclooxygenase on lymphocytes blocked the reaction of soterenol-treated lymphocytes on atria, while inhibitors of lipoxygenase(s) completely blocked the reaction of atria exposed to soterenol-stimulated lymphocytes or supernatants. These results suggest that soterenol reacts with beta 2-adrenoceptors of normal and autoimmune cells. From this reaction, soluble factors are released that in turn trigger stimulation of the atrial contractility as a consequence of the release of oxidative products of the lipoxygenase(s) pathway of arachidonic acid from atria. The high activity of atria in the presence of autoimmune spleen cells is probably related to the increment in number of beta 2-adrenoceptors of these cells. PMID- 2878711 TI - Animal models of Alzheimer's disease: behavior, pharmacology, transplants. AB - Physostigmine, oxotremorine, RS-86, and a combination of piracetam and lecithin, have all been studied in patients with Alzheimer's disease. Intravenous physostigmine produced a significant improvement in patients' ability to recognize words and particularly to distinguish words they had never seen before from words previously presented. A subgroup of Alzheimer's patients had a clinically meaningful improvement to treatment with oral physostigmine, with the degree of improvement correlating with the ability of oral physostigmine to increase the nocturnal secretion of cortisol. No statistically significant differences of piracetam or piracetam and lecithin, compared to placebo were noted, however, the ratio of red cell to plasma choline might be associated with treatment responsivity. The potential therapeutic efficacy of oxotremorine proved all but impossible to assess due to concomitant adverse effects, particularly dysphoria. Results with another cholinergic agonist, RS-86, will be reported. This drug appeared to be better tolerated than oxotremorine. Animals with a kianic acid induced cortical depletion of choline acetyltransferase were found to have a significant impairment in retention of a passive avoidance task, an abnormality that was readily reversible by physostigmine, oxotremorine and 4 amino-pyridine. Cysteamine, a depletor of somatostatin, also produced a comparable deficit. PMID- 2878712 TI - Transmitter-replacement therapy in Alzheimer's disease using intracerebroventricular infusions of receptor agonists. AB - Neurotransmitter replacement therapy in Alzheimer's Disease is currently being attempted using bethanechol chloride (Urecholine) infused intracerebroventricularly with an Infusaid continuous infusion pump. The rationale of this therapy is based on the severe cortical pre-synaptic cholinergic deficit in the presence of relatively normal post-synaptic muscarinic receptor density. Patients are selected on the basis of strict clinical criteria at a functional stage 4 or 5 of Reisberg. A cortical biopsy at the time of pump and catheter implantation confirms the diagnosis by histological and biochemical examination. Pre-operative, post-operative and serial mental status assessments combined with functional ADL assessments monitor changes in behavior. A 6 months double-blind treatment period is done in every patient, who is then free to continue if he has improved on active treatment. This specific study is part of a multi-centre trial. Other therapeutic trials using somatostatin analogs, such as Sandostatin, could then be done. The biological effects of the latter compound are being studied currently in adult Green Vervet monkeys, prior to its use in Alzheimer patients. Furthermore autoradiography of bethanechol and peptides labeled with 14C administered in these animals by intracerebroventricular infusion will allow a better knowledge of their pharmacological site of action. PMID- 2878713 TI - Post-mortem neurochemical changes in Alzheimer's disease compared with normal ageing. AB - Selective neuronal degeneration with concomitant changes in neurotransmitter systems are features of both normal ageing and Alzheimer's disease. There are, however, important neurochemical differences in cerebral cortex. Choline acetyltransferase declines with age in frontal cortex in contrast to the prominent change in the temporal cortex in Alzheimer's disease. The loss of somatostatin, and the recently reported reciprocal change in corticotropin releasing factor and receptors are not seen with ageing. However, age itself may have an important influence on the neurochemical deficits in Alzheimer's disease which are restricted in the older patients. The problems of post-mortem studies in the analysis of ageing and possible approaches to this are discussed. PMID- 2878714 TI - Neurotransmitter and receptor deficits in senile dementia of the Alzheimer type. AB - Multiple neurotransmitter systems are affected in senile dementia of the Alzheimer's type (SDAT). Among them, acetylcholine has been most studied. It is now well accepted that the activity of the enzyme, choline acetyltransferase (ChAT) is much decreased in various brain regions including the frontal and temporal cortices, hippocampus and nucleus basalis of Meynert (nbm) in SDAT. Cortical M2-muscarinic and nicotinic cholinergic receptors are also decreased but only in a certain proportion (30-40%) of SDAT patients. For other systems, it appears that cortical serotonin (5-HT)-type 2 receptor binding sites are decreased in SDAT. This diminution in 5-HT2 receptors correlates well with the decreased levels of somatostatin-like immunoreactive materials found in the cortex of SDAT patients. Cortical somatostatin receptor binding sites are decreased in about one third of SDAT patients. Finally, neuropeptide Y and neuropeptide Y receptor binding sites are distributed in areas enriched in cholinergic cell bodies and nerve fiber terminals and it would be of interest to determine possible involvement of this peptide in SDAT. Thus, it appears that multi-drug clinical trials should be considered for the treatment of SDAT. PMID- 2878715 TI - High resolution chromosome and DNA analysis in multiple endocrine neoplasia type II syndrome. AB - Multiple endocrine neoplasia type II (MEN-II or Sipple's syndrome) is an autosomal dominant disorder characterized by medullary thyroid cancers, pheochromocytomas, and parathyroid adenomas. A blind analysis of high resolution G-banded chromosomes was performed on blood specimens from eight MEN-II individuals from three unrelated families and six control subjects. Seven of eight MEN-II patients and one of six control subjects were determined to have a deletion at 20p12.2. These findings support the hypothesis that MEN-II patients have a 20p12.2 deletion (chi 2 = 6.99; p less than 0.01). Genomic DNA from seven of the eight MEN-II patients was studied using the DNA probe, D20S5, localized by in situ hybridization to 20p12. The probe binding site is not deleted in some MEN II patients, as demonstrated by the presence of two alleles detected as restriction fragment length polymorphisms. Thus, D20S5 does not hybridize to DNA sequences that are deleted based on cytogenetic analysis in MEN-II patients. PMID- 2878716 TI - Chromosome 13 instability and esterase D expression in an osteosarcoma cell line. AB - In order to assess the involvement of the 13q14 region in the development of osteosarcoma, both osteosarcoma tumor cells and normal tissue from a retinoblastoma patient previously used in restriction fragment length polymorphism studies, and sarcoma cells and normal fibroblasts from other tumor patients, have been investigated with respect to esterase D (E.C. 3.1.1.1) expression and chromosome pattern. In spite of an increased number of apparently normal chromosomes #13, a 50% reduction in esterase D activity in osteosarcoma cells from the retinoblastoma patient was observed. This suggests that loss of the RB1 gene or an OSRC gene closely linked to the ESD and RB1 gene loci is involved in the development of the osteosarcoma tumor. No reduction in esterase D expression was seen in four other sarcoma cell lines. PMID- 2878717 TI - Development of adult T-cell leukemia-like disease in African green monkey associated with clonal integration of simian T-cell leukemia virus type I. AB - Proviral integration of a simian retrovirus highly homologous to human T-cell leukemia virus type I was examined in cellular DNAs extracted from primary peripheral blood lymphocytes of 31 adult African green monkeys (Cercopithecus aethiops) that were seropositive for simian T-cell leukemia virus type I (STLV I). Among these monkeys, one case with overt leukemia, showing pleomorphic leukemia cells similar to those in human adult T-cell leukemia (ATL), and five cases in a preleukemic state of ATL-like disease were found. Judging from the integration site of the provirus genome, primary lymphocytes of these leukemic or preleukemic cases contained monoclonally proliferated STLV-I-infected cells, whereas lymphocytes of other seropositive monkeys without hematological abnormalities were polyclonal, and those of seronegative monkeys did not contain the provirus. The restriction patterns with PstI ans SstI of most STLV-I proviruses were identical to those of the previous isolate from this species, but in three monkeys there was a deletion of one PstI site. From the correlation of the development of simian ATL-like disease with the monoclonal integration of the STLV-I provirus genome, it should be indicated that STLV-I has similar leukemogenicity to human T-cell leukemia virus type I, and so STLV-I infection in African green monkeys will be useful as an animal model of human ATL. PMID- 2878718 TI - Treatment of malignant endocrine pancreatic tumors with human leukocyte interferon. AB - Twelve patients with malignant endocrine pancreatic tumors refractory to cytotoxic treatment were treated with human leukocyte interferon im at daily doses of 3 X 10(6)-6 X 10(6) IU. Ten of 12 patients showed an objective response with a mean duration of 15.2 months, median, 11 months (range, 2-36+). All ten patients had a decrease in tumor markers and an objective reduction in tumor size was also noted in four. Improvement of clinical manifestations was seen in all cases with an objective response. Adverse effects, including influenza-like syndrome, reduction of blood cells, and chemical signs of liver dysfunction occurred, but were reversible or could be circumvented by dose reduction. One patient developed hypothyreosis on an autoimmune basis; another patient developed liver steatosis. Although the number of patients is small, the results are promising. Interferon therapy seems to be as potent as cytotoxic treatment but with far less side effects. This study indicates that further trials with interferon in patients with less advanced stages of malignant endocrine pancreatic tumor should be performed. PMID- 2878719 TI - High-performance liquid chromatographic assay for taxol in human plasma and urine and pharmacokinetics in a phase I trial. AB - Taxol is a unique antineoplastic agent which appears to exert its cytotoxic action as a result of interference with microtubular structure and function. Clinical development of this drug will be facilitated by the availability of sensitive and specific methods for its quantitation in biological fluids. We have developed a reverse-phase high-performance liquid chromatographic assay for taxol capable of detecting concentrations as low as 50 nM, which can be automated using readily available equipment. With this assay we have performed pharmacologic studies of taxol during the conduct of a phase I trial of this compound at The Johns Hopkins Oncology Center. Following a 60- to 360-minute infusion, the plasma disappearance is biexponential, with harmonic mean alpha half-life and beta half life values of 16.2 minutes and 6.4 hours, respectively. Volumes of distribution for the theoretical central compartment (VDc) and at steady state (VDss) were 8.6 and 67.1 L/m2. Mean plasma clearance was 253 ml/minute/m2. Urinary clearance was 29.3 ml/minute/m2 and 5.9% +/- 8.8% of the drug was identified in 48-hour urine collections. No metabolites have been identified. Over the 18-fold dose range studied, there was no evidence of nonlinearity or dose-dependent behavior. A rough correlation between area under the plasma disappearance curve and hematologic toxicity was observed. PMID- 2878720 TI - [Drug therapy of dilated cardiomyopathy]. PMID- 2878721 TI - [Neurohumoral mechanisms in the physiopathology of coronary occlusion]. PMID- 2878722 TI - Pain control in dentistry: opioids and analgesic combinations. PMID- 2878723 TI - Subsidiary class III effects of beta blockers? A comparison of atenolol, metoprolol, nadolol, oxprenolol and sotalol. AB - The electrophysiological effects of various concentrations of atenolol, metoprolol, nadolol, D-oxprenolol, L-oxprenolol, and D, L-oxprenolol and D sotalol, L-sotalol, and D, L-sotalol were compared in rabbit right ventricular papillary muscle studied in vitro using intracellular microelectrodes. An assessment of the relative beta blocking effects of D-sotalol and D, L-sotalol against the inotropic action of isoprenaline was made in the same preparation. Of the drugs tested, only oxprenolol and sotalol showed prolongation of action potential duration and effective refractory period (class III action), with oxprenolol showing, in addition, depression of maximal upstroke velocity and the presence of post-repolarisation refractoriness (class I action). When contrasted at clinically relevant concentrations, only sotalol retained a class III effect, without any actions on variables related to fast inward current. The effects of oxprenolol and sotalol were not found to be stereospecific. The mechanical experiments indicate that, in this preparation, D-sotalol has approximately one fourteenth of the beta blocking potency of the racemic compound. It therefore merits further consideration as a useful alternative class III antiarrhythmic agent, which would be free from the side effects of beta receptor blocking treatment. PMID- 2878724 TI - Effects of beta blocking agents on the density of beta adrenoceptors and adenylate cyclase response in human myocardium: intrinsic sympathomimetic activity favours receptor upregulation. AB - The density of beta adrenoceptors, the relative number of beta 1 and beta 2 adrenoceptor subtypes, and adenylate cyclase activity were studied in preparations from atrial biopsy specimens of 32 patients with coronary heart disease. Six patients were not receiving beta blocking agents, whereas the others were treated with different beta blocking drugs (timolol, propranolol, pindolol, metoprolol, and atenolol). Clinical and haemodynamic variables were similar in the different groups of patients. Beta adrenoceptor density was 17% significantly lower in the non-treated group than in the groups treated with beta blocking drugs. Among these, the group treated with pindolol, a drug with intrinsic sympathomimetic activity, had receptor densities that were 38% significantly higher than those treated with other beta blocking drugs and 51% significantly higher than the non-treated group. The relative numbers of beta 1 and beta 2 adrenoceptor subtypes were very similar in the different groups (beta 1 receptors 75-80%, beta 2 receptors 20-25%). A significant increase in the ratios of terbutaline stimulated to basal and terbutaline stimulated to isoproterenol stimulated adenylate cyclase activities was found in patients treated with beta 1 selective blockers (metoprolol, atenolol), indicating that beta 1 selective drugs may improve beta 2 receptor-adenylate cyclase coupling. In contrast, pindolol caused a significant reduction in the ratio of terbutaline stimulated to isoproterenol stimulated adenylate cyclase activity, indicating that this drug may cause a reduction in beta 2 receptor-adenylate cyclase coupling efficacy. Thus treatment with beta blocking agents causes upregulation of human myocardial beta receptor density. Intrinsic sympathomimetic activity seems to favour receptor upregulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878725 TI - Therapeutic rounds: neuroleptic malignant syndrome. PMID- 2878727 TI - Stress-related mucosal damage. AB - Stress-related mucosal damage (SRMD) of the upper gastrointestinal tract is being increasingly recognized in critically ill patients. Its precise pathogenesis is unknown. Acid is a prerequisite for the development of mucosal injury. However, mucosal defense factors that maintain the integrity of the gastric mucosal barrier are equally important. Therapy is directed toward reducing the intraluminal acid concentration. Since histamine H2-receptor antagonists became available in 1977, they have been used for the prevention and treatment of SRMD. They offer the potential for use as an effective parenteral as well as oral agent that could obviate the need for frequent antacid administration and eliminate some of the troublesome side effects that accompany an intensive antacid regimen. Although the beneficial effects of H2 blockers are probably related to their ability to inhibit acid secretion, recent evidence suggests that they may also act by mechanisms independent of their antisecretory effect. Numerous controlled studies have confirmed that cimetidine, being superior to placebo and equivalent to antacids, is effective therapy for SRMD. Sucralfate, a basic aluminum salt of sucrose octasulfate, has been shown to protect animal and human gastric mucosa from a variety of injurious agents. However, few clinical trials have evaluated the efficacy of sucralfate in SRMD. Exogenous prostaglandins also have been shown to protect gastric mucosa from a variety of insults. Although exogenous prostaglandins may work by augmenting mucosal defense mechanisms, most clinical studies have used antisecretory doses of prostaglandin drugs, making it difficult to discount the antisecretory component as being responsible for efficacy. PMID- 2878726 TI - Synergistic interaction between an H2-receptor antagonist and enprostil on 24 hour intragastric pH, serum gastrin concentration, and tissue immunoperoxidase staining for gastrin, somatostatin, and serotonin in a patient with metastatic gastrinoma. AB - A 56-year-old woman newly diagnosed as having Zollinger-Ellison syndrome due to a metastatic gastrinoma underwent 24-hour intragastric pH monitoring, serum gastrin (total, G-17 and G-34) measurements, and immunoperoxidase staining of duodenal, antral, and gastric body biopsies for gastrin, somatostatin, and serotonin. Determinations were made while the patient was given different doses of ranitidine, enprostil (a synthetic orally administered prostaglandin E2), or ranitidine plus enprostil. Following are the findings from this single-patient study: Intragastric pH was persistently low but varied in response to food when the patient was given ranitidine. Immunocytochemical staining of antral biopsies obtained before the patient was treated revealed a reduced number of cells containing G-17 and G-34 but an increase in the antral somatostatin-containing D cells. Treatment with 35 micrograms of enprostil BID plus 300 mg of ranitidine BID for two and 11 weeks was associated with an increased number of duodenal G cells, a decrease in antral D-cells, and a decrease in the number of antral serotonin-containing cells. Enprostil in a dosage of 35 or 70 micrograms BID had no effect on intragastric pH, but when enprostil was given in combination with ranitidine, postprandial and nocturnal intragastric alkalinity was accentuated along with a return of duodenal and antral G-cells and a loss of the antral D cell hyperplasia. Optimal pH control was achieved with 300 mg of ranitidine BID; more frequent dosing with ranitidine did not further increase intragastric pH. Both the total serum gastrin concentration and G-17 levels fluctuated in response to meals. The serum concentrations of total gastrin, G-17, and G-34 were reduced with enprostil and with ranitidine. PMID- 2878729 TI - Safety: cimetidine and concomitant theophylline or warfarin--drug interactions and their implications. AB - Theophylline and warfarin are two drugs whose interactions with cimetidine may have clinically significant effects. Therefore, recent efficacy studies comparing cimetidine 800 mg at bedtime (HS) with 300 mg QID included studies of interactions between cimetidine and these agents. Thirty healthy men were stratified into three age groups: 18 to 35, 36 to 53, and 54 to 70 years and were given 300 mg QID of anhydrous theophylline sustained-action tablets. When steady state was reached (nine days), cimetidine was begun concomitantly in a dosage of 300 mg QID or 800 mg HS for ten days. Three days after cimetidine was started, morning and evening trough theophylline serum levels were monitored. The area under the theophylline serum level-time curve (AUC) was determined on days 5 and 10 of the cimetidine regimen. Upon discontinuation of cimetidine, morning and evening trough serum theophylline levels were measured to determine when all subjects had returned to precimetidine steady-state conditions. A new baseline AUC was then obtained and concomitant administration of the alternate cimetidine regimen was started. Serum theophylline levels were measured as with the first cimetidine regimen. Theophylline was continued for an additional ten days with monitoring of trough levels, after the second cimetidine regimen was completed. AUC was measured after precimetidine steady-state conditions were reached. Steady state theophylline levels were increased less by the 800-mg HS cimetidine regimen than by the 300-mg QID regimen. Although both regimens significantly (P less than 0.05) increased the theophylline AUC and maximum serum concentration (Cmax) in all age groups, the effect of cimetidine 800 mg HS was significantly less for all subject data combined and particularly for the oldest groups of subjects, indicating that the theophylline-cimetidine interaction is age-related. New theophylline steady-state levels were achieved by day 5 of concomitant cimetidine administration, and precimetidine theophylline serum trough levels, Cmax, and AUC were observed five days after discontinuation of both cimetidine regimens. The effects of the same two cimetidine regimens on the pharmacodynamics and pharmacokinetics of warfarin were also evaluated in 25 patients stabilized on anticoagulant therapy. The preliminary data indicate that patients with a baseline prothrombin time ratio (PTR) of less than 2.0 would not be expected to exceed a PTR greater than 2.5 after two weeks of concomitant administration of cimetidine at either dosage.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2878728 TI - A dosage alternative for H2-receptor antagonists--constant infusion. AB - Control of gastric acid is accomplished either by buffering it with antacids or by preventing acid secretion with H2-receptor antagonists. Advantages of antacids are their rapid onset of action and the possibility of precisely titrating intragastric pH. In practice, however, they are cumbersome to use because they must be administered frequently (often hourly) and thus require excessive nursing time. In addition, their use often leads to undesirable side effects, such as diarrhea. Cimetidine and ranitidine are H2-receptor antagonists that differ primarily in their potency, ranitidine being four to ten times more potent than cimetidine. With either drug, the patient's intragastric pH falls below 5 by about the fourth hour after the dose. One way to avoid the peaks and valleys of acid secretory control is to use constant infusion. Infusion rates of 50 mg/hr of cimetidine preceded by loading doses of 300 mg of cimetidine often produce a constant intragastric pH above 5. It is essential that intragastric above 5. It is essential that intragastric pH be checked and infusion rates increased or antacids added if pH drops below 5. Bauer used constant infusion of cimetidine in patients with upper gastrointestinal bleeding. He found constant infusion more successful, but his end-point was merely to stabilize the patient before surgery. At UC Davis, we compared constant infusion with intermittent dosing (300 mg of cimetidine every six hours) in patients admitted to the intensive care unit with upper gastrointestinal bleeding. PMID- 2878730 TI - Immunohistochemical evidence for a magnocellular somatostatin cell group in the anterior paraventricular thalamus of the rat. AB - By use of the indirect immunofluorescence technique a small group of large somatostatin-positive neurons is described in the subependymal area of the anterior paraventricular thalamus of the male rat. Retrograde-tracing experiments suggest that they project to areas outside the blood-brain barrier. PMID- 2878731 TI - [Experimental study on natural infection, biting and transovarial transmission of epidemic haemorrhagic fever virus in gamasid mites]. PMID- 2878732 TI - [The microtiter agglutination test for detection of pertussis antibody using a stained bacterial suspension]. PMID- 2878733 TI - A trans Golgi-derived exocytic coated vesicle can contain both newly synthesized cholinesterase and internalized transferrin. AB - We used a cholinesterase-mediated density shift protocol to investigate the movement of internalized transferrin (Tf) through endo- and exocytic coated vesicles (CVs) in the perfused rat liver. Upon internalization, exogenous 125I-Tf was found in endocytic CVs but not in cholinesterase-containing (i.e., exocytic) CVs (0-40 min). Between 1 and 2 hr, 125I-Tf began to appear in exocytic CVs. The origin of the exocytic CV was further investigated. After perfusion of the liver with asialotransferrin, the exocytic CVs were shown to contain resialylated Tf, indicating that the trans Golgi was the origin of this class of CVs. The resialylated Tf accumulated in the extracellular medium with kinetics very similar to the time course for appearance of Tf in cholinesterase-containing, exocytic CVs, suggesting that these CVs are directly involved in the transfer of material from the trans Golgi to the cell surface. PMID- 2878734 TI - [Substitution of fluphenazine decanoate with oxyprothepine decanoate in long-term maintenance therapy in schizophrenia]. PMID- 2878735 TI - Intestinal absorption of a beta-adrenergic blocking agent nadolol. I. Comparison of absorption behavior of nadolol with those of other beta-blocking agents in rats. PMID- 2878737 TI - Biochemical aspects of the mechanism of action of antiarrhythmic drugs on mitochondria. VII. Effect on energy-linked reactions and on membrane potential. AB - Effects of the antiarrhythmic drugs (propranolol, perhexiline maleate, lidoflazine and iproveratril) on energy-linked reactions and on membrane potential were studied. Propranolol, perhexiline maleate and lidoflazine inhibit the ATPase activity of undamaged and broken mitochondria, and of submitochondrial particles. All drugs are inhibitors of either ATP-driven or of succinate-driven reduction of NADP+. The antiarrhythmics promote a decrease in the membrane potential upon energization of the mitochondrial membrane by alpha-ketoglutarate, succinate, or ATP. It was suggested that these drugs have a primary action on the mitochondrial membrane, thus altering the activities of membrane proteins (channels and enzymes). PMID- 2878738 TI - Subtypes of beta-adrenergic receptors in bovine coronary arteries. AB - Whether large coronary artery dilation induced by beta-adrenergic stimulation is mediated by beta 1- or beta 2-adrenergic receptors remains controversial. This problem is particularly difficult to address in vivo due to the concomitant increase in coronary blood flow with beta-adrenergic stimulation, which by itself can dilate large coronary arteries. To reconcile this problem, 5 calves were instrumented with intraaortic and intracoronary (i.c.) catheters, ultrasonic diameter transducers, Doppler flow transducers, and hydraulic occluders on the left circumflex coronary artery. Two to six weeks following surgery, beta adrenergic agonists were administered i.c. to avoid complicating systemic effects. Isoproterenol (0.0025 micrograms/kg, a beta 1 + beta 2-adrenergic agonist) increased coronary diameter (7.1 +/- 0.8% from 5.80 +/- 0.58 mm) (p less than 0.01). Similar increases (p less than 0.01) in coronary diameter occurred with prenalterol (0.4 micrograms/kg, beta 1-adrenergic agonist) (9.5 +/- 1.4%) and pirbuterol (0.25 micrograms/kg, beta 2-adrenergic agonist) (8.1 +/- 1.2%). When coronary blood flow was prevented from rising with the hydraulic constrictor, increases in coronary diameter to all three beta-adrenergic agonists were not attenuated. Large coronary artery dilation with prenalterol and pirbuterol was abolished with beta 1- and beta 2-adrenergic receptor blockade, respectively, while neither beta 1- nor beta 2-adrenergic blockade alone abolished the large coronary artery dilation with isoproterenol. To identify the predominant subtype of beta-adrenergic receptor, competitive inhibition curves utilizing 125I-cyanopindolol (125I-CYP) as the radiolabel versus isoproterenol, epinephrine, and norepinephrine were generated in membrane preparations from calf heart (predominant beta 1), calf lung (predominant beta 2) and calf coronary artery. The coronary artery membrane preparations demonstrated an intermediate pattern. Competition curves with selective beta 1- and beta 2-adrenergic receptor agonists and antagonists again demonstrated a pattern for coronary artery intermediate to that of heart and lung, further confirming the presence of both beta-adrenergic receptor subtypes in large coronary arteries, with a ratio of beta 1: beta 2 of 1.5-2.0:1.0. Thus, large coronary arteries of the calf contain both beta 1- and beta 2-adrenergic receptors identified utilizing ligand binding techniques, and stimulation of both receptor subtypes in the intact conscious animal results in large coronary artery dilation, independent of blood-flow mediated vasodilation. PMID- 2878736 TI - Fibrinogen and fibrin: biochemistry and pathophysiology. AB - Fibrinogen is a thrombin-coagulable glycoprotein occurring in the blood of vertebrates. The primary structure of the alpha, beta, and gamma polypeptide chains of human fibrinogen is known from amino acid and nucleic acid sequencing. The intact molecule has a trinodular, dimeric structure and is functionally bivalent. Thrombin cleaves short peptides from the amino termini of the alpha and beta chains exposing polymerization sites that are responsible for the formation of fibrin fibers and appearance of a clot. The major physiological function of fibrinogen is the formation of fibrin that binds together platelets and some plasma proteins in a hemostatic plug. In pathological situations, the network entraps large numbers of erythrocytes and leukocytes forming a thrombus that may occlude a blood vessel. Fibrinogen and fibrin are multifunctional proteins. Fibrinogen is indispensable for platelet aggregation; it also binds to several plasma proteins, however, the biological function of this interaction is not completely understood. Fibrin is an essential matrix for regulation of fibrinolysis and for facilitation of cell attachment in wound healing. PMID- 2878739 TI - [A cellulose acetate membrane counter immunoelectrophoresis test for identification of the host source of mosquito blood meals]. PMID- 2878740 TI - [Inoculation of microfilariae of Brugia malayi into four species of mosquitoes]. PMID- 2878741 TI - Central nervous system effects of beta-adrenergic-blocking drugs: the role of ancillary properties. AB - Among the side effects commonly reported with the use of beta-blockers are symptoms related to the central nervous system (CNS). In this study we compared the effects of four beta-blockers with different ancillary properties (atenolol, metoprolol, propranolol, and pindolol) and placebo on objective and subjective measures of CNS function in 30 healthy male subjects. All subjects were randomly assigned to a double-blind, placebo controlled, Latin-square design study in which five 1 week periods of drug or placebo administration were separated by 2 week washout periods. Laboratory evaluations were conducted at the end of each treatment period, and included multistage exercise stress testing; questionnaire assessments of mood state, sexual function, and sleep habits; tests of psychomotor function; and overnight polysomnographic measures of sleep. Significant effects on sleep continuity were observed for each of the lipophilic drugs, as reflected in the number of awakenings (pindolol = 6.4 +/- 5.0; propranolol = 6.3 +/- 3.2; metoprolol = 7.2 +/- 4.7; atenolol = 3.6 +/- 2.9; placebo = 3.9 +/- 2.7) and time of wakefulness (pindolol = 20.6 +/- 27.0 min; propranolol = 15.5 +/- 23.0 min; metoprolol = 19.5 +/- 24.3 min; atenolol = 10.2 +/- 11.6 min; placebo = 9.2 +/- 74.5 min). Only pindolol significantly affected rapid eye movement (REM) sleep time (pindolol = 54.5 +/- 21.9 min; placebo = 74.5 +/- 74.5 min) and REM latency (pindolol = 175.0 +/- 60.7 min; placebo = 95.4 +/- 43.8 min). Subjective reports of sleep similarly indicated increased wakefulness and greater restlessness with lipophilic beta-blockers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878742 TI - Hemodynamic effects of the beta 1-adrenoceptor partial agonist xamoterol in relation to plasma norepinephrine levels during exercise in patients with left ventricular dysfunction. AB - A new cardioselective beta 1-adrenoceptor partial agonist, xamoterol, has been developed for the treatment of heart failure, especially that associated with ischemic heart disease. To investigate the hemodynamic effect of xamoterol in relation to sympathetic nervous activity, hemodynamic variables and plasma norepinephrine (NE) levels were measured at rest and during three graded bicycle exercise tests before and after a single intravenous dose of 0.15 mg/kg xamoterol in 10 patients with mild-to-moderate left ventricular dysfunction. Plasma NE increased with increasing grade of exercise and a linear correlation between plasma NE and heart rate was observed at four time points (at rest and three exercise levels) before and after xamoterol. After administration of xamoterol, the slope of the regression line of plasma NE-heart rate relation was significantly less steep than that before drug. Predose and postdose regression lines crossed at 440 pg/ml of plasma NE. Similar effects were observed on the plasma NE-cardiac index and plasma NE-systolic blood pressure relations (regression lines crossed at 380 and 530 pg/ml of plasma NE, respectively). Thus, xamoterol had a dual agonist-antagonist effect in relation to plasma NE, and the crossover point lay approximately between 400 pg/ml and 500 pg/ml. This level of plasma NE was achieved at a low exercise level and at a heart rate of about 100 beats/min. These results indicate that xamoterol has intrinsic sympathomimetic activity comparable to relatively low sympathetic activity (400 to 500 pg/ml of plasma NE) and therefore acts as a beta 1-agonist when sympathetic nervous activity is below this level and as an antagonist when sympathetic activity is above this level. PMID- 2878743 TI - Rational therapies for hypertension. Is step 1 of stepped care archaic? PMID- 2878744 TI - In vitro studies upon the release of gamma-glutamyltransferase from human liver. AB - Samples of human liver have been incubated in different fluids for up to 48 h and the released gamma-glutamyltransferase studied by gel chromatography on Sephacryl S-300 and polyacrylamide gradient gel electrophoresis. When human liver is incubated in serum, most of the released enzyme is of high Mr (greater than 1,000,000). Incubation in hepatic bile, or in a solution of glycochenodeoxycholate, results in the release of enzyme that is hydrophobic in nature and which reaggregates to a varying extent after the removal of bile salts. In contrast, incubation in saline, or in a solution of human albumin results in the release of a hydrophilic low Mr (about 120,000) form of the enzyme. These observations are discussed in relation to possible mechanisms for the release of these multiple forms. PMID- 2878745 TI - Effect of LHRH treatment on testicular descent and hormonal response in cryptorchidism. AB - In a double-blind placebo-controlled study in 49 boys with cryptorchidism the effect of intranasal synthetic LHRH was studied. After 8 weeks improvement in testicular location was found in 13 testes (37%), but this improvement was considered sufficient of only six testes. Placebo resulted in an improved location in 18% of the testes. The mean change in testicular position (expressed in cm) after LHRH therapy was slightly greater than after placebo but only in the squatting position did this difference reach significance. Aggressive behaviour was reported in 23% of the children treated with LHRH. A second LHRH course did not result in significant improvement in any of the patients. At follow-up reascent was frequently seen. The final results in unilateral cryptorchidism are poorer than those in bilateral cryptorchidism. LHRH therapy leads to higher plasma LH levels and a lower FSH in response to an intravenous LHRH test. In 15 boys plasma testosterone levels rose above 0.4 nmol/l. We conclude that intranasal LHRH application has a limited value for the treatment of cryptorchidism but may be suitable as a diagnostic test. PMID- 2878747 TI - Effects of somatostatin analogue SMS 201-995 in normal man. AB - Long-acting somatostatin analogues may be of benefit in certain hypersecretory endocrine and gastrointestinal disorders. The 24 h hormonal and metabolic profiles of six normal male subjects receiving a twice daily subcutaneous injection of one such analogue SMS 201-995, 50 micrograms, has been compared to that obtained following placebo injection. Spontaneous daytime peaks of GH secretion were delayed until 1400 h following SMS 201-995 but nocturnal and total 24 h GH secretion were unaffected. The nocturnal rise in thyrotrophin was abolished by SMS 201-995 but thyroid function was unaffected. Insulin levels were suppressed following SMS 201-995 and the response to meals was inhibited. Glucose intolerance followed main meals. Glucagon levels were suppressed for up to 6 h. Circulating alanine levels were raised between 1200 h and 0600 h and there were intermittent elevations in lactate, pyruvate, glycerol and 3-hydroxybutyrate. Amino acid levels, including branched chain amino acids, were also increased. All six subjects suffered gastrointestinal side-effects. SMS 201-995, 50 micrograms, given twice daily shortly before meals does not suppress 24 h GH secretion, but demonstrates significant effects on metabolism and causes side effects in normal subjects. PMID- 2878748 TI - The sensitivity of growth hormone and prolactin secretion to the somatostatin analogue SMS 201-995 in patients with prolactinomas and acromegaly. AB - The somatostatin analogue SMS 201-995 has recently been shown to be effective in suppressing GH secretion in most acromegalic patients. In the present study it was investigated whether PRL release in prolactinoma and acromegalic patients might also be sensitive to SMS 201-995 and whether co-secretion of PRL in acromegaly plays a role in determining the sensitivity of GH secretion to SMS 201 995. The s.c. administration of 50 micrograms SMS 201-995 did not affect high plasma PRL levels in four microprolactinoma patients. Therapy of one of these patients for 3 d with 50 micrograms three times a day also did not affect PRL levels. The single administration of 50 micrograms SMS 201-995 in 22 acromegalic patients lowered plasma GH levels for 2-6 h to less than 5 micrograms/l in 14 patients and to less than 50% of control values in 16 patients. In 18 of these 22 patients the immunohistochemical picture of the pituitary tumour was known. Eleven patients had pure GH-containing tumours and in seven patients there were mixed GH/PRL-containing tumours. In two of these latter patients there was evidence for GH and PRL being secreted by the same tumour cells. The sensitivity of GH secretion to SMS 201-995 did not differ between the patients with pure GH or mixed GH/PRL-containing adenomas. Plasma PRL levels were not affected by SMS 201-995 in the patients with pure GH-secreting tumours, but were significantly suppressed in four of the seven patients with mixed GH/PRL containing tumours. Chronic treatment for 16 weeks of one patient with a mixed GH/PRL-containing tumour with SMS 201-995 (100 micrograms three times a day) resulted in normalization of both the increased GH and PRL levels. It is concluded that SMS 201-995 does not affect tumorous PRL secretion in patients with pure prolactinomas. In acromegalic patients with mixed GH/PRL-containing tumours PRL secretion in some patients is sensitive to SMS 201-995, making these patients good candidates for chronic treatment with the analogue. The simultaneous presence of PRL in the GH-secreting pituitary tumour or the presence of hyperprolactinaemia in acromegalics does not play a role in the sensitivity of GH secretion to the somatostatin analogue. PMID- 2878746 TI - Somatostatin and oxytocin infusion inhibits the rise of plasma beta-endorphin, beta-lipotrophin and cortisol induced by insulin hypoglycaemia. AB - The present study investigated the possible effect of somatostatin and oxytocin on the basal and stress-induced rise of beta-endorphin (beta-END), beta lipotrophin (beta-LPH) and cortisol in the human. For this purpose somatostatin (4.1 micrograms/min for 120 min or oxytocin (0.4 micrograms/min for 120 min) was infused into two different groups of seven healthy subjects; 30 min after the start of the infusion, placebo or insulin (0.1 IU/kg body weight, B.W.) was injected on two different days. In a third experimental step, an insulin tolerance test was performed during saline infusion to evaluate stress-related effects on the different hormonal secretions under basal conditions. Plasma levels of beta-END, beta-LPH and cortisol were measured by radioimmunoassay. Extraction and chromatographic procedures preceded the assay for beta-END and beta-LPH. Neither somatostatin nor oxytocin significantly modified basal plasma levels of beta-END, beta-LPH and cortisol. However these treatments blunted the rise of the three hormones seen at 45 and 60 min during insulin-induced hypoglycaemia (P less than 0.01). These results indicate that somatostatin and oxytocin may influence the beta-END, beta-LPH and cortisol increase induced by stress in humans, without affecting their basal secretion. PMID- 2878750 TI - A study into possible deviation from the Hardy-Weinberg equilibrium by the alleles of the hypervariable sequence in the region of the human insulin gene. AB - A number of studies have reported on possible relationships between a hypervariable sequence near the 5' end of the insulin gene and some common diseases. Control populations within these studies appear to disobey the Hardy Weinberg equilibrium. In this study we have ascertained the allele frequencies in 181 random individuals. The chi-squared statistic comparing this population with a theoretical Hardy-Weinberg population was 0.61. This makes it unlikely that in the general population the Hardy-Weinberg rule is disobeyed. Possible reasons for the discrepancy between our study and the studies of others are discussed. PMID- 2878749 TI - Analysis of fragile X-mental retardation families using flanking polymorphic DNA probes. AB - Fragile-X mental retardation (FRAX-MR) is one of the more common X-linked disorders affecting 1 in 1,500 newborn males. This disease is characterized by the expression of fragile site in the region q27.3 of the X-chromosome of affected boys when their lymphocytes are cultured in folate deficient medium. In most patients there is macroorchidism postpubertally. The clinical diagnosis of carrier females based on the expression of fragile site in Xq27.3 is usually difficult and sometimes impossible. About half of the carrier females escape diagnosis by this method. Furthermore, prenatal diagnosis is not always feasible. Using Restriction Fragment Length Polymorphism (RFLP) and cloned DNA segments from the region Xq27-Xqter as probes, we have investigated Swedish families with FRAX-MR in three generations. Interesting observations, previously unreported to our knowledge, have been made in some patients and carrier mothers, using one of the probes which is localized to the distal end of Xq. The significance of these findings and the linkage of the disease locus to the different probes used in this study is presented. PMID- 2878751 TI - The cardiovascular effects of trimazosin and prazosin in the rabbit. AB - The cardiovascular effects of trimazosin, a quinazoline derivative similar in structure to prazosin, were investigated and compared with prazosin in the rabbit. Radioligand binding to cerebral membranes showed that trimazosin has roughly 100-fold less affinity for the alpha 1-adrenoceptor. This was further supported by its lower pA2 derived from phenylephrine contractile responses in isolated thoracic aorta preparations. Trimazosin is less extensively distributed and has a lower clearance from whole blood than prazosin although their whole blood elimination half-lives are comparable. In addition, although it is a less potent alpha 1-adrenoceptor antagonist in vivo, its peripheral vascular depressor effect tends to be greater than prazosin. Trimazosin at the dose used and under the conditions of study did not reverse the peripheral pressor effect of angiotensin II or B-HT920 but at higher concentrations, unlike prazosin, it relaxed the K+ contracted thoracic aorta. In addition, following pharmacological autonomic blockade and treatment with prazosin in vivo, trimazosin caused a further depressor response. A similar though shorter lasting non-alpha 1-receptor mediated action was also observed with prazosin. 1-Hydroxytrimazosin (CP23445), the major metabolite of trimazosin in man, showed little affinity for either the alpha 1- or alpha 2-adrenoceptor from radioligand binding studies. In addition to alpha 1-adrenoceptor antagonism, trimazosin may exert an additional direct vasodilator effect in rabbits. PMID- 2878752 TI - The histopathologic classification of cutaneous lymphomas. AB - A classification of malignant lymphomas has been formulated to identify distinct clinical groups of patients for future therapeutic trials. The unifying concept of primary cutaneous lymphomas as of either T- or B-cell origin does not conflict with the Working Formulation but encompasses its categories. This classification requires immunologic data in addition to morphologic assessment for accurate evaluation. Cytomorphologic subdivision of the cutaneous T-cell lymphomas does not have the same clinical significance as for the cutaneous B-cell lymphomas. However, the pattern of skin involvement in cutaneous T-cell lymphoma (epidermotropic versus nonepidermotropic) does appear to be important clinically and should be included in future classifications. PMID- 2878753 TI - Pathogenesis of cutaneous T-cell lymphoma. AB - Cutaneous T-cell lymphoma is a malignant disease whose behavior reflects its T cell lineage. The biologic characteristics of the disease are understandable when viewed from a perspective of normal T-cell-skin interactions. Thus, it is of no surprise that this malignancy of helper T lymphocytes usually demonstrates a remarkable affinity for the skin at the outset and that, coincident with decreased dependence upon this unique environment, the extent and aggressiveness of disease increases. Although the inciting event responsible for the development of cutaneous T-cell lymphoma is unknown, a mechanism for local growth and distant expansion of malignant cells has been postulated in terms of IL-2-dependent and independent growth phases. As our vision into the cellular and subcellular workings of this malignancy becomes more acute, specific therapeutic and preventive measures will emerge. PMID- 2878754 TI - Retroviruses and lymphoproliferative disease. AB - This article has provided an introduction to and a brief overview of recent developments in the investigation of retroviruses and their role in animal and human neoplasia. The sheer volume of new information concerning this subject is nearly overwhelming. We can only hope that this knowledge will eventually lead to major therapeutic advances. PMID- 2878755 TI - Clinical features of cutaneous T-cell lymphoma. AB - The distinctive clinical features and natural history of mycosis fungoides, an epidermotropic variant of cutaneous T-cell lymphoma, are presented. These findings are compared with certain non-mycosis fungoides T-cell lymphomas that occasionally occur in the skin. Clinical staging and evaluation of patients with cutaneous lesions including plaques, tumors, or erythroderma, with or without nodal involvement and disseminated disease, are considered. Associated disorders such as follicular mucinosis, actinic reticuloid, lymphomatoid papulosis, and secondary primary malignancies are also presented. PMID- 2878756 TI - [A case of syndrome malin with persistent cerebellar signs]. PMID- 2878757 TI - Life-threatening complications of betamimetic therapy for preterm labor inhibition. AB - Betamimetic administration for inhibition of preterm labor can result in a number of severe complications for the mother. An understanding of clinical situations that increase the risk of complications and suggested treatment of adverse effects are discussed in this review. PMID- 2878758 TI - Clinical leukocyte phenotyping by laser flow cytometry and monoclonal antibodies (immunocytometry) in renal transplantation. AB - Absolute levels of peripheral blood mononuclear cells were sequentially monitored by immunocytometry in 54 consecutive renal allograft recipients receiving azathioprine/prednisone (STD gp, N = 16) or cyclosporine with or without prednisone (CsA gp, N = 38), before and after transplantation. In the CsA group, but not in those receiving STD therapy, the mean absolute levels of all but OKT4+ cells increased significantly with the duration of therapy. In both treatment groups (STD + CsA), the mean % delta OKT4/8 ratio increased from a prerejection quiescent value of 80 +/- 6% SE to a rejection value of 120 +/- 6% (P less than .001) and fell back to 77 +/- 6% (P less than .0005) in postrejection quiescence. The sensitivity and specificity of such an elevated ratio for rejection were 84.4% and 88.6%, while positive and negative likelihood ratios were 7.40 and 0.15, respectively. In rejection, concomitant immunopathology showed a predominance of OKT8+ cells in the graft with a mean T cell subset ratio of 0.8 +/- 0.3 SE in renal biopsies compared to 2.0 +/- 0.3 for circulating cells (P less than .0125). Parallel donor-antigen-specific assay of lymphocyte-mediated cytotoxicity (LMC) became positive with graft rejection. Immunocytometry with normalization of sequential data in longitudinal analysis thus appears to be a valuable tool in immunologic laboratory monitoring of graft rejection. PMID- 2878759 TI - Case report: renovascular hypertension in Takayasu's disease treated by percutaneous transluminal angioplasty. AB - Systemic hypertension secondary to renal artery stenosis is a common complication of Takayasu's disease. A case of Takayasu's disease is presented, in which hypertension was relieved by percutaneous transluminal angioplasty of a unilateral renal artery stenosis. PMID- 2878760 TI - Pharmacotherapy of chronic obstructive pulmonary disease. AB - The pharmacologic treatment of the reversible elements of chronic obstructive pulmonary disease is discussed in this article. Discussion focuses on three classes of bronchodilator drugs--the sympathomimetic agents, the methylxanthines, and the anticholinergic agents. A section on corticosteroid use in patients with chronic airflow limitation is included. An integrated approach to pharmacotherapy is suggested that allows a treatment program to be designed to meet the needs of the individual patient. PMID- 2878761 TI - COPD: causes, treatment, and risk for lung cancer. PMID- 2878762 TI - Diagnosis and treatment of headache disorders. PMID- 2878763 TI - New concepts in the management of asthma. PMID- 2878764 TI - Reduction of dental fear: psychophysiological correlates. AB - EMG, HR and SCR were continuously recorded during two Standardized Dental Examinations (SDE) of 15 dental phobics. Following the first SDE, the patients were assigned to two treatment groups, one receiving systematic desensitization followed by two separate amalgam restorations and one premedicated with Valium for the two restorations. The dentist rated the patients' behavior on a 5-point scale. Corah's Dental Anxiety Scale (DAS) was used prior to the first SDE and following the second SDE. The second SDE was conducted on a separate occasion following the second restoration. No significant correlations were found between any of the physiological measures and either the dentist's ratings or the second DAS or DAS change scores. Significant differences found between the two treatment groups on the dentist's ratings, second DAS, and change scores were not reflected by the physiological measures. PMID- 2878765 TI - Sex steroid binding protein from Bufo arenarum: further characterization. AB - The effects of temperature, pH, divalent cations, 2-mercaptoethanol (Et-SH), N ethylmaleimide (NEM), and phenylmethylsulfonyl fluoride (PMSF) on the dihydrotestosterone (DHT) binding to sex steroid binding protein from Bufo arenarum (baSBP) were examined. The temperature curve indicated that the binding remained stable up to 50 degrees C and the pH curve showed maximum binding between pH 7 and 9. The incubations of baSBP with divalent cations, NEM and Et-SH demonstrated that baSBP require disulfides and sulfhydryl groups for steroid binding or to maintain an adequate protein conformation. On the other hand, PMSF had no effect on the binding, consequently, serine residues appear not to be involved in DHT binding to baSBP. These results indicate that baSBP has a behavior resembling that of human SBP. PMID- 2878766 TI - Transmural potential difference and short circuit current of chicken cecum in vitro. AB - The electrical parameters of the chicken cecum were studied in vitro, in birds fed a commercial NaCl-rich diet. The statistical analysis of data was carried out using a linear model-based method which enabled standardization of concomitant factors that could mask the interpretation of the results. Transmural potential difference (PD) decreased initially reaching stable values at 50 min between 7.9 and 9.0 mV. Short-circuit current (Isc) was stable during incubation, with lower values in the medial (41.8 microA/cm2) than in the distal (58.1 microA/cm2) region of the cecum. The reduction of Na+ concentration in the incubation medium produced a fall in PD and Isc and both were ouabain and amiloride sensitive. This indicates that the current is largely carried by the net Na+ transport. PMID- 2878767 TI - Influence of diet on the storage, mobilization and utilization of energy reserves in trained and untrained rats. AB - The effect of the major dietary energy source (fat or carbohydrate) on some of the adaptations to physical training, particularly body composition and tissue glycogen concentrations, were studied in growing male Wistar rats. Resting liver glycogen concentrations were lower in both trained and sedentary rats fed a high fat diet compared to corresponding rats fed a high carbohydrate (low fat) diet. Trained rats on both diets had higher liver glycogen levels than corresponding sedentary controls. Resting gastrocnemius muscle glycogen concentrations were not influenced by diet or training. Rates of liver and muscle glycogen depletion during a 60-min swim were lower in trained rats but were not influenced by diet. Significant interactions were noted between the dietary energy source and exercise training with respect to body weight gain, body fat content, liver weight and liver glycogen concentrations. PMID- 2878768 TI - Uric acid uptake in erythrocytes of beagle and dalmatian dogs. AB - Uric acid uptake by erythrocytes of Beagle and Dalmatian dogs has been measured, using (2-14C) uric acid. Uptake was characterized by a fast and a slow component. Urate uptake was inhibited by certain purine and pyrimidine derivatives and by anion transport inhibitors. It was dependent on intraerythrocyte glycolysis. Temperature only influenced uptake by the slow component (Q10 = 2.6). Urate uptake by the slow component is apparently due to the transport into the erythrocytes by facilitated diffusion (Km = 6.6 mmol/l, Vmax = 390 mumol/l/min), whereas the fast component exhibits an adsorption of urate on erythrocyte surface. No difference of urate uptake by erythrocytes of Beagle and Dalmatian dogs has been observed. PMID- 2878769 TI - Competition for cool nasal blood between trunk and brain in hyperthermic goats. AB - An influence of brain and trunk temperatures controlled independently of each other by means of artificial heat exchangers, on the intensity of natural selective brain cooling (SBC) was studied in 6 conscious goats. Intensity of SBC was markedly enhanced by increasing brain temperature. On the other hand, a rise of trunk temperature with the cerebral temperature clamped at 39 degrees C or 40 degrees C, reduced SBC intensity in spite of a simultaneous increase in the respiratory evaporative heat loss. When brain temperature was clamped at 41 degrees C, the magnitude of SBC was essentially independent of trunk temperature. These results suggest that during hyperthermia a competition exists between trunk and brain for cool nasal blood. PMID- 2878770 TI - Interrelationships among epidermal Na-K ATPase, developmental stage and length of Rana catesbeiana tadpoles. AB - Sodium and potassium activated adenosine triphosphatase (Na-K ATPase) was extracted from the skin of Rana catesbeiana tadpoles and adults. Using carefully staged tadpoles, it was noted that the enzyme level increases two or three stages before there is a perceptible potential difference generated across the skin. The level of non-ouabain-inhibitable ATPase remains constant throughout the life cycle. It was also concluded that Rana catesbeiana tadpoles cannot be reliably staged using length as a key trait. PMID- 2878771 TI - Changes in haematological parameters associated with capture and captivity of the marine teleost, Pleuronectes platessa L. AB - After capture by trawling, the blood parameters of plaice (Pleuronectes platessa L.) are perturbed for up to 5 days post-capture. Whole blood values recovered from an initial stress-induced haemoconcentration within 12 hr. There is a marked hyperglycaemia following capture: blood glucose concentration increased four-fold to 87.92 +/- 10.41 mg/100 ml (N = 6) after 12 hr and remained elevated for 3-4 days before returning to normal values. Monovalent blood electrolytes (Na+, K+, Cl-) significantly increased during the initial stages post-capture (4-10 hr) but then recovered. The divalent cations (Ca2+, Mg2+) similarly increased but for a longer period (24-72 hr). Liver and muscle glycogen concentrations were very variable during the recovery period. All blood parameters achieved stable values within 5 days of capture. This study provides comprehensive haematological data on post-trawl recovery and tank-acclimation in plaice, for up to 28 days following capture. PMID- 2878772 TI - Body composition of Atlantic salmon (Salmo salar L.) studied by neutron activation analysis. AB - This paper describes the measurement of whole body Ca, Cl, K, N, Na, O and P in Atlantic salmon parr, adults and kelts by neutron activation analysis (NAA). This technique is based on counting the specific gamma activity in samples which is present naturally or is produced by neutron irradiation. Body composition (fat, mineral, protein and water) are estimated from these data. NAA has advantages over chemical methods with the potential for in vivo measurements. Anthropogenic 137Cs was found in sea-water (SW) salmon but not found in the freshwater (FW) stages (parr and kelts). Presence of this isotope in fish caught in FW indicates recent SW residence. PMID- 2878773 TI - Kidney clearance of D- and L-tryptophan by rats. AB - Renal clearances of D-tryptophan and of L-tryptophan by rats were compared. Both D- and L-tryptophan were reabsorbed by the rat kidney tubules very efficiently. Compared to the rapid excretion of D-tryptophan by the chick, the good retention of this isomer by the rat kidney might be responsible for its efficient utilization by rats. PMID- 2878774 TI - Changes in plasma phosphate with the stimulation of anaerobic metabolism in rats during hypoxic-anoxic states. AB - Exposure of rats to high altitude hypoxia causes a rapid decrease in plasma Pi: this change reached the maximum value after exposure to an altitude of 6000-7000 m. Lactate increased markedly when rats were exposed to a high altitude, above 5500-6000 m, although no increase in lactate was observed on exposure to an altitude below 5500 m. Highly anoxic conditions including cyanide and carbon monoxide poisoning cause a marked increase in inorganic phosphate (Pi) and lactate in plasma. Pi entering the intracellular spaces can be utilized as the substrate of oxidative phosphorylation during exposure to an altitude below 5500 6000 m, and for glycolytic enhancement in rats exposed to an altitude above 6000 m. The increase in plasma Pi may be explained by the inhibition of mitochondrial oxidation and the degradation of high energy phosphate compounds under highly anoxic conditions. PMID- 2878776 TI - Plasma ferritin and other parameters related to iron metabolism in piglets. AB - The evolution of mean plasma ferritin values, hematocrit, hemoglobin, plasma iron concentration and total plasma iron binding capacity were studied during the growth of piglets from 0 to 50 days. The results obtained point to a massive mobilization of iron from storage sites during the second and third weeks of life of these animals. Apart from plasma ferritin values and the total plasma iron binding capacity, the coefficient of utilization may be considered as another parameter to be taken into account upon evaluating iron deposits in piglets. PMID- 2878775 TI - The nature of thyrotropin stimulation of thyroid function in Japanese quail: prolonged thyrotropin exposure is necessary to increase thyroidal 125I uptake. AB - Single injections of thyrotropin (TSH) increase serum T4 and thyroidal 32P uptake but not thyroidal 125I uptake regardless of dosage, exposure time or age. Chronic TSH exposure, with 3 or more days of injection, does increase thyroidal 125I uptake. Studies using iodine (I) supplementation indicated that the increased thyroidal radioiodine uptakes seen with chronic TSH administration were not due to an I deficiency in the thyroid resulting from high hormone release. Labeled and unlabeled experiments comparing the effects of single vs. multiple injections of TSH were used to describe the effects of TSH on hormone release, hormone production and thyroidal I uptake. PMID- 2878777 TI - Epithalamus of the nine-banded armadillo, Dasypus novemcinctus. AB - The epithalamus of embryonic, neonatal and adult nine-banded armadillo (Dasypus novemcinctus) was examined for evidence of pineal-like tissue. The evagination of the diencephalic roof (the anlage of the epiphysis) was not found in any embryonic specimens. In the adult brain, the epithalamus is dominated by the sub commissural organ (SCO) which is surrounded entirely by the posterior commissure. At the most caudal aspect of the SCO, previous investigators have observed pineal like tissue. Using pineal-specific staining techniques however, we found no evidence of this tissue. Because the armadillo produces melatonin in a rhythmic manner, exhibits exacting circadian rhythms, and shows altered rhythms when exposed to exogenous melatonin, we believe other organs, perhaps the retina or Harderian gland, must be involved in maintaining the coordinated melatonin titer. PMID- 2878778 TI - Somatostatin immunoneutralization affects plasma metabolite concentrations in the domestic fowl. AB - Young leghorn cockerels were injected with antiserum to somatostatin (anti-SRIF) and plasma glucose, free fatty acids and alpha-amino nitrogen concentrations determined. Plasma glucose concentrations increased rapidly after anti-SRIF and remained high for up to 2 hr. Two different antisera tested had hyperglycaemic activity. Plasma free fatty acids also increased rapidly after administration of the two different anti-SRIFs, and remained high for about 1 hr. Plasma alpha amino nitrogen increased during the first 30 min after anti-SRIF, then declined to levels significantly lower than control by 1-2 hr after injection. Anaesthesia reduced plasma concentrations of glucose and alpha-amino nitrogen, and also reduced the changes of these metabolites following anti-SRIF. The results show the importance of endogenous somatostatin in the regulation of plasma metabolite concentrations. PMID- 2878779 TI - Photoperiodic adjustment of thermal conductance in deer mice. AB - Seasonal changes in metabolic rate can be induced in mice held in thermal neutral (26-29 degrees C) ambient temperatures. The metabolic effect of winter photoperiod is a lower metabolic rate without compromise to metabolic reserve. Manipulations of photoperiod or melatonin backgrounds adjust the thermoregulatory setting for core temperature level and affect thermal conductance. PMID- 2878780 TI - Taste receptor mechanism of salts in frog and rat. AB - Salts carrying impermeable organic cations elicited large responses in the frog and rat taste nerves. Amiloride suppressed the responses of the frog and rat taste nerves to NaCl, KCl and the organic salts to a similar extent. The estimated equilibrium potentials for Na+ and K+ at the thresholds determined were more negative than the resting potentials of the taste cells. The results obtained suggest that the taste responses to salts including NaCl are not induced by entry of cations via apical membranes of taste cells. PMID- 2878781 TI - Effect of temperature on the seasonal production of testicular androgens, in vitro, by the lizard Tiliqua rugosa. AB - The effect of temperature on the seasonal production of testicular androgens, in vitro, was examined in the scincid lizard Tiliqua (Trachydosaurus) rugosa. Testicular tissue was incubated, in vitro, at various temperatures (18, 25, 32 and 37 degrees C). Endogenous androgens, testosterone and epitestosterone, were measured by radioimmunoassay. Epitestosterone production was maximal at 37 degrees C and minimal at 18 degrees C. There was no consistent effect of incubation temperature on testosterone production. Incubation temperature had no effect on the seasonal pattern of androgen production. The results suggest that temperature may play a part in the regulation of androgen biosynthesis in T. rugosa. PMID- 2878782 TI - Tolerance of chick embryos to low temperatures in reference to the heart rate. AB - Ten-day-old embryos were exposed to 28, 18 and 8 degrees C environments and their electrocardiograms (ECG) monitored. Embryos in 28 and 18 degrees C environments maintained a constant heart rate averaging 97 and 25 beats/min, respectively, followed by arrhythmias and cardiac arrest at 101 and 59 hr. Embryos in an 8 degrees C environment went into cardiac arrest after 2-4 hr, but recovered 20 hr later upon rewarming to 38 degrees C. Six to 20-day-old embryos exposed to 8 degrees C were examined for tolerance time after cardiac arrest. The younger the embryo the longer its tolerance to prolonged cardiac arrest. PMID- 2878783 TI - Activities of chitinase and protease and concentration of fluoride in the digestive tract of Antarctic fishes feeding on krill (Euphausia superba Dana). AB - Studies on the digestion of krill by Notothenia rossii marmorata, Notothenia neglecta, Champsocephalus gunnari and Chaenocephalus aceratus showed that these Antarctic fish species are well equipped to feed on krill, as indicated by their high levels of chitinase and protease activity. Very high chitinolytic activities were determined in the stomach of the fish species. However, activities that were measured in intestine samples can be substantial, as well. Very strong protease activities were determined in samples of the stomach tissue and the intestinal contents. When krill were present in the guts, the concentrations of fluoride in the stomach and intestinal contents of N. rossii marmorata and Ch. gunnari were extremely high, while the tissues were practically devoid of fluoride. PMID- 2878784 TI - The effect of immunization against somatostatin on growth rates and growth hormone secretion in the chicken. AB - The effect of both active passive immunization against somatostatin on growth rate and growth hormone levels was studied in chickens. Passive immunization against somatostatin by administration of antiserum had no effect on rate of growth of chickens and no persistent effect on circulating growth hormone (GH) levels. In acute experiments, administration of anti-somatostatin serum caused a marked elevation of GH levels in chickens at both 4 and 8 weeks of age, but the relative stimulation was greater in the older birds. Active immunization against somatostatin significantly stimulated growth rate in chickens, but was not shown to have a clear effect on circulating GH levels. These data suggest that somatostatin control over GH secretion may not be fully developed in the chicken at 4 weeks of age, but that immuno-neutralization of somatostatin can produce an increase rate of growth in chickens similar to that seen in mammals. PMID- 2878785 TI - Intramitochondrial inclusions in the kidney of the pygmy mouse. AB - Intramitochondrial inclusions averaging 1000 A in diameter were observed in the cells of the proximal convoluted tubules in samples of kidneys from pygmy mice, Baiomys taylori. Electron microscopic study of unstained sections and mitochondrial fractions showed that these inclusions are lipid and found at a S.G. 1.37 in a linear sucrose gradient. Renal glycogen, inorganic phosphate and plasma sodium were significantly higher in the pygmy mouse and plasma calcium was lower, as compared with the laboratory mouse. We believe these intramitochondrial inclusions to be lipid which accumulates divalent cations, particularly calcium, which acts as a sodium pump allowing the pygmy mouse to conserve water and adapt to its environment. PMID- 2878786 TI - The thermal physiology of two sympatric treefrogs Hyla cinerea and Hyla chrysoscelis (Anura; Hylidae). AB - Metabolic rates, temperature acclimation, lipid deposition and temperature tolerance were investigated in two species of hylid treefrogs, the green treefrog (Hyla cinerea) and the coastal plain (Cope's) gray treefrog (Hyla chrysoscelis). The rate of oxygen consumption at rest differed between the two species only at 30 degrees C; there was no difference in respiratory metabolism at lower ambient temperatures. Hyla cinerea generally completed metabolic acclimation earlier than H. chrysoscelis, particularly at high temperatures; both species appeared to be fully acclimated in 6 days or less. The gray treefrog is less tolerant of high ambient temperatures than the green treefrog; mean upper lethal temperature was 41.5 degrees C for Hyla chrysoscelis and 43.7 degrees C for H. cinerea. Metabolized energy was higher at high ambient temperatures (i.e. 29 degrees C) for H. chrysoscelis than H. cinerea, while the reverse was true at 19 degrees C. The coefficient of utilization (100 X metabolized energy/gross energy intake) did not vary significantly between species or within species over the ambient temperature range of 19-24 degrees C; H. chrysoscelis had a significantly higher efficiency at 29 degrees C. Lipid reserves were generally similar in the two species throughout the summer. Differences in behavior, seasonal variation in activity and timing of reproduction are all related to thermal physiology and may play a role in determining the distributional limits of the two species. PMID- 2878787 TI - Ontogeny of alpha-amylase circadian rhythms in rat parotid gland. AB - The content of alpha-amylase (alpha-1,4-glucan-4-glucanohydrolase, EC 3.2.1.1.) and total soluble proteins of parotid glands (from rats exposed to a photoperiod of 14 hr light: 10 hr dark), have been determined every 2 or 3 hr over 24 hr periods in 15, 25 and 90-day-old rats. In 35-, 45- and 72-day-old rats, determinations were performed only at 0100 and 1400 hr. The alpha-amylase and total soluble protein contents from 90-day-old rats show a circadian variation, with a maximum value at 2200 hr and a minimum at 1400 hr. Parotids from 15- and 25-day-old rats also show a circadian rhythm. The minimum value is recorded at 0100 hr and the maximum at 1400 hr. At day 35 and after, there is an inversion of the amylase rhythm. In immature rats, it appears that alpha-amylase and soluble protein are under the influence of another synchronizer, whose timing is independent of that imposed by mastication of solid food. PMID- 2878788 TI - Elevated testosterone level in response to clomiphene in male Anolis carolinensis. AB - Anolis carolinensis were used as experimental models to study the short-term effects of the fertility drug, clomiphene citrate, on male squamate reproductive function. Daily injections of 10.0 micrograms of clomiphene induced an increase in plasma testosterone over a 5 day period. No change in testis mass or morphology was elicited over this time. PMID- 2878789 TI - Metabolism of exogenous androgens in rams and wethers: differential clearance rates. AB - The effect of the presence of the testes on the clearance rates of 5 and 50 mg of testosterone and androstenedione was examined in 8-month old rams and wethers. Castration did not affect (P greater than 0.10) the clearance of androstenedione or testosterone at the 5 mg dosage. Castration had an effect (P less than 0.05) on the clearance of 50 mg of androstenedione and testosterone. These data indicate that reproductive status has a differential effect on the metabolism of exogenously administered steroids. PMID- 2878790 TI - Effect of caging singly or in groups of different sizes on the thermogenic activity of interscapular brown adipose tissue in mice. AB - The effects on the thermogenic activity of brown adipose tissue of caging mice singly or in groups of different sizes has been investigated. At 23 degrees C the total cytochrome oxidase activity and the level of mitochondrial GDP binding were higher in mice caged singly than in mice caged in groups of three or six. At 4 degrees C GDP binding and cytochrome oxidase activity were lower in mice caged in groups of two, three or six than in mice caged singly. The mitochondrial concentration of uncoupling protein was not clearly affected by the number of mice in each cage. PMID- 2878791 TI - Colloid osmotic pressure changes in human whole blood and separated plasma in vitro with changes in CO2 content and pH. AB - Colloid osmotic pressure (COP) and pH were measured on the true plasma of human blood from five subjects tonometered with different concentrations of carbon dioxide. Measurements were also made on their separated plasma. COP (mmHg) of true plasma obtained from tonometered whole blood varied in proportion to the bicarbonate concentration (mEq/l): COP = 0.056 [HCO3-] + 23.3. In separated plasma, as CO2 concentration increased, COP decreased as pH decreased: COP = 1.99 (pH) + 11.0. When the change in COP due to the change in pH was subtracted from the observed change of COP due to CO2 exposure of whole blood, the difference was the change of COP due to the shift of fluid between plasma and red cells: COP adjusted for pH = 0.131 [HCO3-] + 21.5. The COP values of tonometered whole blood and separated plasma are taken to be equal at a pH of 7.40 (at the mixed venous point). The change in COP, adjusted for pH, for a given change in pCO2 is in keeping with the amount of fluid shift calculated from the measured changes in hematocrit and plasma protein concentration. An error in a previous paper (Kakiuchi et al., J. appl. Physiol. 44, 474-478, 1978) had led to an overestimation of the COP change from the exposure of whole blood to CO2 in vitro. PMID- 2878792 TI - Analysis of drug-tubulin interaction by trypsin cleavage: comparison for colchicine, podophyllotoxin, griseofulvin, vinblastine and taxol. AB - Trypsin preferentially cleaves the alpha subunit of depolymerized tubulin or vinblastine induced aggregates (in which longitudinal interactions between tubulin molecules could take place). No cleavage was found for tubulin polymerized into microtubules (containing lateral and longitudinal tubulin interactions), in the presence of taxol. In the presence of colchicine or podophyllotoxin the alpha subunit was partially protected from proteolytic digestion. Trypsin digestion pattern varied upon the addition of different concentrations of griseofulvin. At the higher concentration used, in which microtubules assembly was inhibited, both tubulin subunits were cleaved. PMID- 2878793 TI - Regulation of intracellular protein turnover: covalent modification as a mechanism of marking proteins for degradation. PMID- 2878794 TI - The molecular genetics of human T cell leukemias and lymphomas. PMID- 2878795 TI - Mammalian cell transformation by a recombinant murine retrovirus containing the avian erythroblastosis virus erbB gene. PMID- 2878796 TI - Gonadotropin and androgen levels in patients operated upon for cryptorchidism. AB - 53 patients previously operated upon for cryptorchidism were examined seven years (range 2-18) after the operation. We measured serum levels of sex-hormone-binding globulin (SHBG), testosterone (T), free testosterone (free T), dihydrotestosterone (DHT), 4 androstenedione (4-AD), and dehydroepiandrosteronesulphate (DHAS), and the gonadotropin luteinizing hormone (LH) and follicular hormone stimulating (FSH). Compared to normal controls, there were decreased levels of free testosterone and DHT and increased levels of SHBG and DHAS. The FSH levels were elevated and LH values low. No relationship was found between androgen and gonadotropin levels, suggesting that the normal feed back mechanism is malfunctioning. There were no hormonal differences between patients with previous unilateral and bilateral cryptorchidism, although SHBG levels were higher in the former. We concluded that cryptorchidism is probably due to a defect in the hypothalamic-pituitary axis and not to a primary defect in the testes. PMID- 2878797 TI - Evidence that PGE2 stimulates intestinal epithelial cell adenylate cyclase by a receptor-mediated mechanism. AB - These studies were performed to examine whether prostaglandin E2 stimulates intestinal epithelial secretion via a receptor-mediated or non-receptor-mediated activation of adenylate cyclase. Solubilization of epithelial cell adenylate cyclase with Lubrol PX, which separates the receptor moiety of the cyclase from the remainder of the complex, inhibited the prostaglandin E2 stimulation of the cyclase. A similar result was obtained with VIP, which activates adenylate cyclase via a receptor-mediated mechanism, whereas fluoride, gamma S-GTP, and forskolin, which activate the cyclase via non-receptor-mediated mechanisms, all stimulated solubilized adenylate cyclase. In addition, prostaglandin E2 and VIP both showed a dependence on GTP for adenylate cyclase stimulation while fluoride and forskolin did not. These data suggest that prostaglandin E2 activates intestinal mucosal adenylate cyclase by a receptor-mediated mechanism. The presence of such receptors lends support to the possibility that prostaglandins have a physiological role in the control of mucosal transport. PMID- 2878799 TI - Neural anatomy, chemistry and event-related brain potentials: an approach to understanding the substrates of mind. PMID- 2878800 TI - Neuroregulators and electrical activity: transmitter and modulator influence on the cortical cholinergic system. PMID- 2878798 TI - Fluoxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. AB - Fluoxetine is a new antidepressant which enhances serotoninergic neurotransmission through potent and selective inhibition of neuronal reuptake of serotonin. Metabolism by N-desmethylation occurs in man yielding desmethylfluoxetine, which also inhibits serotonin reuptake. Both the parent compound and metabolite possess elimination half-lives of several days facilitating the maintenance of steady-state plasma concentrations during long term treatment. Fluoxetine has overall therapeutic efficacy comparable with imipramine, amitriptyline and doxepin in patients with unipolar depression treated for 5 to 6 weeks, although it may be less effective than tricyclic antidepressants in relieving sleep disorders in depressed patients. Geriatric patients also responded as well to fluoxetine as to doxepin. The symptomatic improvement in patients with unipolar depression during short term fluoxetine treatment has been satisfactorily maintained when therapy was extended for at least 6 months: the relapse rate was low and similar to that of imipramine. Preliminary data have shown that patients with bipolar depression gained similar therapeutic benefit from fluoxetine or imipramine. Other preliminary trials have indicated that fluoxetine may be useful in obsessive-compulsive disorders. Usual doses of fluoxetine cause significantly fewer anticholinergic-type side effects than tricyclic antidepressants. Nausea, nervousness and insomnia are the most frequently reported fluoxetine-related adverse effects, but these have usually not been severe. Therapeutic doses of fluoxetine do not affect cardiac conduction intervals in patients without pre-existing cardiovascular disease and fluoxetine has been relatively safe in the small number of patients who have taken overdoses. It has not been clearly established whether some types of depression may respond more readily to fluoxetine than other antidepressants, and its overall therapeutic efficacy has not been compared with other second generation antidepressants. Thus, with its different and perhaps improved side effect profile compared with older tricyclic antidepressants, fluoxetine offers properties that could be used to advantage in many patients with depression. PMID- 2878801 TI - [Anticholinergics during neuroleptic treatment. Value and withdrawal]. AB - In a study on 144 chronic psychotic patients treated with neuroleptics, the authors tried to define a therapeutic schedule for anti-cholinergic drugs use to control parkinsonism induced by anti-psychotic drugs. Systematic treatment by anti-cholinergic drugs seems to be useless, even dangerous, and, if they have to be employed, the treatment must not exceed six months. The authors emphasize and analyse through the literature, the problems of drug abuse, withdrawal and psychological dependence with anti-parkinsonian drugs and their neurochemical effects. PMID- 2878802 TI - The ischemic infarct pulp of traumatized teeth: a light and electron microscopic study. PMID- 2878804 TI - The value of computed tomography in the localization of undescended testes. AB - Eight patients with unilateral and four with bilateral (4) unpalpable testes were evaluated with CT for localization. All patients were later submitted to laparascopy and/or surgery and 13 cryptorchid testes and 3 atrophic or agenesic testes were found. CT detected correctly 11 of the cryptorchid testes - (85%) with one false positive and one false negative finding. In the three atrophic or agenesic testes, CT did not identify any image suspicious of being a testis, so there three were no false positive studies here. It is concluded that CT is an accurate noninvasive method for the preoperative detection of cryptorchid testes. PMID- 2878803 TI - Genetic and cytogenetic localisation of the homeo box containing genes on mouse chromosome 6 and human chromosome 7. AB - Probes from the m6 homeo box cluster were mapped to mouse chromosome 6 by somatic cell genetics, in situ hybridisation, and by a Mus spretus--Mus musculus backcross mapping system. In addition, the testis-specific homeo box containing cDNA, clone, HBT-1, has been mapped using the same back-cross system and the B X D recombinant inbred strain set. Close genetic and physical linkage between the m6 cluster and HBT-1 was demonstrated, positioning these sequences to the same local cluster of homeo box containing genes. The map location of this cluster between IgK and Tcrb coincides with the morphological mutation hypodactyly (Hd). Synteny has been observed between a region of mouse chromosome 6 and the long arm of human chromosome 7 encompassing the markers Cpa, Tcrb and Try-1. Here we localise human sequences hybridising to the mouse m6 probes to the short arm of chromosome 7, breaking the region of synteny. PMID- 2878805 TI - Taxol induces the formation of unusual arrays of cellular microtubules in colchicine-pretreated J774.2 cells. AB - Taxol is an antimitotic agent with the unique ability to induce the formation of parallel arrays of microtubules in cells. We have studied the effects of taxol on microtubule organization in the cultured macrophage-like cell line, J774.2, and shown that this novel reorganization of cellular microtubules is both a concentration-dependent and time-dependent phenomenon. In this paper, we have examined in detail the unusual microtubule arrays induced by taxol in colchicine pretreated cells. Interphase cells which are pretreated with the irreversible inhibitor, colchicine, and then treated with taxol form a single microtubule aster associated with the nucleus and numerous discrete sites of apparent microtubule nucleation scattered throughout the cytoplasm. One interesting possibility is that these structures represent nucleation sites for taxol-induced bundles, a result supporting the notion that taxol-induced microtubule arrays are organized assemblies at what are perhaps secondary organizing sites. PMID- 2878806 TI - The role of beta blockade in the limitation of infarct development. AB - This review article deals with the role of beta blockade in the limitation of infarct development. A large number of studies have reported that early administration of beta blockers limits infarct size in animals. In a few, however, these results were not reconfirmed. In man, several large randomized trials have shown that early administration of beta blockade limits infarct development judged from serum enzyme activity and ECG recordings. Delay time between the onset of symptoms and start of treatment is of major importance. It appears as though patients with a higher initial rate pressure product respond most favourably. Although these results are encouraging, the role of infarct limitation in relation to effects on early mortality, chest pain and arrhythmias have not been clearly defined. PMID- 2878807 TI - Can beta blockers limit myocardial infarct size? AB - The suggestion that beta blockers can reduce mortality is not in dispute, nor is the undoubted clinical value of this important group of drugs. What must however be questioned is whether these beneficial effects can be, or need be, explained by 'infarct size limitation'. PMID- 2878808 TI - Effects of high doses of insulin on regional blood flows during acute left ventricular failure in dogs. AB - This study describes the effects of high doses of insulin on systemic haemodynamics and regional blood flows during acute ischaemic heart failure in dogs. Left ventricular (LV) dysfunction was induced by embolization of the left main coronary artery, and was evidenced by a significant increase in LV end diastolic pressure and decrease in LVdP/dtmax and cardiac output. Measurements of femoral, renal, mesenteric and carotid blood flows showed a redistribution of cardiac output during failure. Femoral blood flow decreased to a greater extent than cardiac output, but carotid blood flow decreased in proportion to cardiac output, while mesenteric and renal blood flows were moderately reduced in relation to the decrease in cardiac output. Administration of 300 IU of fast acting insulin significantly improved the performance of the failing left ventricle. Cardiac output was raised to levels observed before failure. The greatest increases in peripheral flow occurred in the femoral and carotid vascular beds, while the least occurred in the mesenteric and renal vascular beds. These observations indicate that insulin at high dose levels significantly improves peripheral circulation by positive inotropic and vasodilatating effects. There was a tendency to favour femoral and carotid vascular flows, but not at the expense of renal and visceral flows. Beta receptor blockade blocked neither the systemic nor regional haemodynamic effects of insulin. PMID- 2878810 TI - Effects of beta-blocking agents on urinary excretion of 3-methylhistidine during experimental hyperthyroidism in rats. AB - Beta-blocking agents are increasingly used as preoperative treatment of hyperthyroid patients. Relatively little is known about the effects of these drugs on metabolic alterations in hyperthyroidism. The aim of this investigation was to study the effects of two different beta-blocking agents on the urinary excretion of 3-methylhistidine (3-MH) during experimental hyperthyroidism in rats. Experimental hyperthyroidism was induced by daily intraperitoneal injections of triiodothyronine (T3; 100 micrograms/100 g body weight) for 3 days. Control animals were injected with corresponding volumes of solvent. Groups of rats received food enriched with metoprolol (8.8 mmol/kg of diet) or propranolol (3.3 mmol/kg of diet) or food without additions. Urinary 3-MH excretion was increased by about 40% during experimental hyperthyroidism. A similar increase of 3-MH excretion was found in animals receiving T3 + metoprolol, whereas the excretion of 3-MH was reduced to control level in hyperthyroid rats receiving propranolol. No effects of metoprolol or propranolol on 3-MH excretion were found in control animals. Although the source of 3-MH cannot be exactly defined, the present results indicate that increased proteolysis in skeletal muscle and/or other tissues during experimental hyperthyroidism was reduced by propranolol. PMID- 2878809 TI - Beta-2-adrenoceptor agonists as inhibitors of lung vascular permeability to radiolabelled transferrin in the adult respiratory distress syndrome in man. AB - Increased lung vascular permeability leading to increased plasma protein extravasation and accumulation (PPA) is a characteristic feature of acute lung injury. Using a previously described technique, PPA was monitored in the lungs of patients with the adult respiratory distress syndrome (ARDS)--an extreme example of acute lung injury in man. An external radiation probe detector was used to monitor the pulmonary accumulation of the plasma protein transferrin radiolabelled in-vivo with 113mIn. Ten patients with ARDS exhibiting increased PPA indices (greater than 1.0 x 10(-3)/min) were given an intravenous infusion of terbutaline (7 micrograms/kg) over 30 min. Of the four patients in whom the post drug PPA indices remained within the ARDS range, none survived, whilst five of the six patients in whom the post-drug PPA indices were reduced to below 1.0 x 10(-3)/min survived. PPA indices prior to the administration of terbutaline were not significantly different between the survivor (n = 5) and non-survivor (n = 5) groups. There was a significant decrease in the PPA indices following terbutaline in survivors (p less than 0.01) but not in non-survivors. Thus beta-2-agonists in therapeutic doses can inhibit increased lung vascular permeability in man. These findings may have prognostic and therapeutic implications for beta-2-agonists in ARDS. PMID- 2878811 TI - Treatment of chronic urticaria with terfenadine and ranitidine. A randomized double-blind study in 45 patients. AB - 45 patients with chronic urticaria were randomized to double blind therapy with terfenadine an H1-antihistamine or ranitidine, an H2-antihistamine, or a combination of both drugs. The therapeutic response was assessed by diary scores. The primary effect variable was "itching". The inference-statistical evaluation of the patient scores showed varying therapeutic effects. The Type-I error was p = 0.015. Itching was reported to be significantly lower by patients receiving both drugs than by those who were given terfenadine alone, while ranitidine in monotherapy had no significant effect on itching. A similar trend was seen in assessment of the severity of weals, while the treatment regimens had no influence on swelling. PMID- 2878812 TI - Acute and subacute actions on human performance and interactions with diazepam of temelastine (SK&F93944) and diphenhydramine. AB - Thirteen healthy subjects participated in a combined acute and subacute double blind, cross-over trial of two H1-antihistamines diphenhydramine (DPH) and temelastine (SKF) against placebo. The doses were DPH 50 mg b.d. and SKF 100 mg b.d. Objective (digit symbol substitution, flicker fusion, Maddox wing, attention, tracking, choice reaction) and subjective (visual analogue scales, side-effects on questionnaire) tests were done on Days 1, 4 and 5, on each occasion before drug intake and after 90 min and 3 h. On Day 1 DPH caused clear sedation of unpleasant character and impaired flicker fusion, attention and digit symbol substitution. SKF shifted the VAS assessment "drowsy/alert" towards drowsiness at 90 min, without objective impairment. On Day 4 DPH reduced exophoria and impaired flicker fusion without subjective sedation. On Day 5, diazepam 0.3 mg/kg (DZ) given with the other drugs caused subjective sedation of pleasant character and impaired various functions in the objective tests. Neither SKF nor DPH increased the effects of DZ; DPH slightly counteracted the effect of DZ on exophoria. At home, SKF did not differ from placebo while DPH proved sedative. DPH did not improve sleep but caused dry mouth and blurred vision. Measurement of plasma levels of antihistamines on each test day revealed the development of tolerance to antihistamine-induced sedation. The concentration of DZ measured by bioassay was somewhat elevated in the presence of DPH. Since the majority of the performance tests were not influenced by temelastine, it appears to be an acceptable, novel H1-antihistamine for the treatment of allergic disorders. PMID- 2878813 TI - Stereo- and regioselectivity of hepatic oxidation in man--effect of the debrisoquine/sparteine phenotype on bufuralol hydroxylation. AB - The influence of the debrisoquine/sparteine-type of oxidation polymorphism on plasma bufuralol concentration and the pattern of urine metabolites was studied in extensive and poor metabolizer subjects. (+)- and (-)-bufuralol, and (+)- and (-)-OH-bufuralol in plasma were determined by enantioselective HPLC, and urinary bufuralol and its metabolites were assayed by gas chromatography-mass spectrometry. Three hours after administration of racemic bufuralol the plasma ( )/(+) isomeric ratio for unchanged bufuralol was 1.84 in extensive metabolizers, indicating preferential clearance of the (+)-isomer through aliphatic 1' hydroxylation and glucuroconjugation, while the (-)-isomer was mainly eliminated by aromatic 4-hydroxylation. Poor metabolizers were characterized by impaired 1'- and 4-hydroxylation, with almost total abolition of the stereoselectivity of these reactions. The data strongly suggest that both 1'- and 4-hydroxylation are catalyzed by the same enzyme. These in vivo observations are in agreement with recent in vitro data obtained in human liver microsomes from phenotyped patients and support the concept of deficiency of a highly stereoselective cytochrome P 450 isozyme as the cause of this polymorphism. PMID- 2878814 TI - Bopindolol versus metoprolol in hypertension. PMID- 2878815 TI - Increased responsiveness to stimulation of alpha- but not beta-adrenoceptors in the hereditary cardiomyopathy of the Syrian hamster. Intact adenosine- and cholinoceptor-mediated isoprenaline antagonistic effect. AB - The effects of phenylephrine (in the presence of propranolol) or isoprenaline and of adenosine or carbachol (alone and in the presence of isoprenaline) were studied on the force of contraction in electrically driven papillary muscles isolated from the hearts of cardiomyopathic (strain BIO 8262) and age-matched, healthy Syrian hamsters. All experiments were performed in the so-called prenecrotic stage of the disorder within the first 30 days of life. Phenylephrine exerted a positive inotropic effect in all preparations from the cardiomyopathic hamsters. In contrast, in thirteen preparations from healthy Syrian hamsters, phenylephrine increased force of contraction in only four preparations. The positive inotropic effect of isoprenaline was similar in both cardiomyopathic and healthy Syrian hamsters. Adenosine and carbachol apparently reduced the isoprenaline-induced increase in force of contraction in both cardiomyopathic and healthy Syrian hamsters. We conclude that an increased responsiveness to alpha adrenergic stimulation occurs in the hearts of cardiomyopathic Syrian hamsters and may be related to the myocardial injury occurring in this syndrome. An increased responsiveness to beta-adrenoceptor stimulation or an impaired adenosine-mediated or cholinoceptor-mediated feedback inhibition is unlikely to play a role in the aetiology of this syndrome. PMID- 2878816 TI - Relative activities of SCH 23390 and its analogs in three tests for D1/DA1 dopamine receptor antagonism. AB - Inhibitory activities of a series of analogs of SCH 23390 ((R)-(+)-7-chloro-8 hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine) in which the 7 chloro group was substituted by bromo, fluoro, methyl and methoxy groups, respectively, were compared in three tests for D1 and DA1 dopamine (DA) receptor antagonism: inhibition of DA-induced renal vasodilation in the anesthetized dog (DA1 receptor model), inhibition of DA-stimulated adenylate cyclase in the striatum of adult female rats (D1 receptor model) and displacement of [3H]SCH 23390 in the striatal homogenates of male rats. In addition the D2 receptor affinity of each of the compounds chosen was assessed via displacement of [3H]spiperone binding from rat striatum. S-enantiomers of the Cl and CH3 analogs were 200- to 700-fold weaker than the respective R-enantiomers in all three tests. The activity of all the R-enantiomers was in the nanomolar range and varied no more than 8-fold in all three tests. The F analog in the ligand binding test was the only exception, which was 30-fold weaker than the C1 analog. All of the R-enantiomers studied showed much weaker affinity for the D2 receptor, as assessed by displacement of [3H]spiperone binding. Similar enantiomer selectivity and parallel affinities of the R-enantiomers in the prototype models for D1 and DA1 receptors strengthen the evidence in support of identity between the D1 and DA1 dopamine receptors. These results further indicate that displacement of SCH 23390 in the ligand binding test reflects affinity of a compound for D1 and DA1 dopamine receptors. PMID- 2878817 TI - (-)-Propranolol blocks the inhibition of serotonergic dorsal raphe cell firing by 5-HT1A selective agonists. AB - The ability of the beta-adrenoceptor antagonist propranolol to block the effects of serotonin (5-HT) and 5-HT1A-selective agonists on the spontaneous firing of serotonergic dorsal raphe neurons was assessed. During microiontophoretic application, (-)- but not (+)-propranolol rapidly and reversibly blocked the suppressant effects of the 5-HT1A-selective agonists ipsapirone (TVX Q 7821) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). However, (-)-propranolol was a relatively weak antagonist of 5-HT itself, suggesting that the endogenous neurotransmitter may have actions on dorsal raphe neurons in addition to those mediated by 5-HT1A receptors. PMID- 2878818 TI - Renal vasoconstrictive effect of kinins mediated by B1-kinin receptors. AB - The nature of the renal vascular actions of kinins, their dependence on prostaglandins and B1-kinin receptor responses were studied in functioning isolated perfused rat kidneys (IK). Lysylbradykinin (LBK), 0.28 and 0.7 microM, transiently decreased and then markedly increased the renal vascular resistance (RVR) in a sustained manner. Bradykinin (BK) at the same doses also had a transient vasorelaxant but not a sustained vasoconstrictive effect. The inactivation of LBK and BK by the IK did not account for the transient nature of their vasorelaxant effect. Indomethacin (5 microM) markedly blunted LBK-induced decrease but not increase in RVR. The B1-kinin receptor agonist desArg9-BK (0.4 1.0 microM) did not decrease RVR but, as LBK, markedly increased RVR in a dose related manner. The B1-kinin receptor antagonist [Leu8]desArg9-BK had no effect on its own but inhibited the desArg9-BK-induced vasoconstriction in a stoichiometric manner. This antagonist at 4.0 microM also completely abolished the vasoconstrictive effect of 0.7 microM LBK, whereas it potentiated and prolonged its vasorelaxant effect. The results demonstrate that kinins, particularly LBK, have bimodal effects on the renal vascular resistance of the isolated perfused rat kidney. The vasorelaxant effect is at least partly mediated by prostaglandins whereas the vasoconstrictive effect of LBK and/or its renal metabolites has the typical character of a B1-kinin receptor response. It is postulated that B1-kinin receptor responses may be of importance in the generation and/or maintenance of renal vasoconstriction in disease states which lead to renal failure. PMID- 2878819 TI - Antagonism of the emetic action of xylazine by alpha-adrenoceptor blocking agents. AB - The intramuscular injection of xylazine (2 mg/kg) evoked vomiting in 81% of the dogs studied. Adrenoceptor antagonists showing alpha 2-blocking activity, yohimbine, tolazoline and phentolamine, antagonized the xylazine-induced vomiting in a dose-dependent manner. Of these antagonists, yohimbine was the most effective, since the maximal antagonistic effect was seen at 0.5 mg/kg yohimbine, a dose at which the other drugs had less or no effect. The adrenoceptor antagonists showing alpha 1-blocking activity, prazosin and phenoxybenzamine, at the doses studied did not prevent the emesis induced by xylazine. A beta adrenoceptor antagonists, propranolol, was ineffective in reducing xylazine induced vomiting. The dopamine receptor antagonists, metoclopramide and domperidone, did not prevent xylazine-induced vomiting nor did yohimbine antagonize apomorphine-induced vomiting. The xylazine-induced vomiting was not prevented by atropine, naloxone or hexamethonium. These results indicate that the xylazine-induced vomiting is mediated by alpha 2-adrenoceptors and does not appear to involve beta-adrenoceptors, cholinoceptors, dopamine or opiate receptors in the emetic pathway. PMID- 2878820 TI - High affinity [3H]zolpidem binding in the rat brain: an imidazopyridine with agonist properties at central benzodiazepine receptors. AB - [3H]Zolpidem, a novel hypnotic drug possessing a chemical structure unrelated to that of benzodiazepine (BZD) was employed as a new ligand to determine its binding characteristics to membrane preparations of rat cerebral cortex and cerebellum. In both structures, the imidazopyridine [3H]zolpidem bound with high affinity to a single population of recognition sites. The cerebellum possessed a similar number of [3H]zolpidem and [3H]diazepam binding sites, while the cerebral cortex possessed a lower density of [3H]zolpidem than [3H]diazepam binding sites. In contrast to [3H]diazepam binding, [3H]zolpidem binding was not detectable in the spinal cord. In the cortex, BZDs had a similar potency to displace [3H]zolpidem and [3H]diazepam binding while non-BZDs were more potent to inhibit [3H] zolpidem binding than [3H]diazepam binding. The binding of [3H]zolpidem was enhanced by GABA to the same extent as [3H]diazepam binding. The increase in [3H] zolpidem binding caused by chloride ions was less pronounced than that in [3H]diazepam binding. It is concluded that [3H]zolpidem possesses selectivity for BZD receptors with the pharmacological characteristics and regional distribution of the BZD1 receptor subtype. [3H]Zolpidem as a radioligand offers a useful additional tool to study the mechanism of action of hypnotics acting through BZD receptor subtypes. PMID- 2878821 TI - Co-localization of tyrosine hydroxylase and phenylethanolamine-N methyltransferase immunoreactivity in the rat retina: a re-examination using double labeling on semi-thin sections. AB - The precise morphology and distribution of phenylethanolamine-N-methyltransferase (PNMT)-immunoreactive cells has been observed and compared with the previously described tyrosine hydroxylase (TH)-immunoreactive cells, in the rat retina. The PNMT-positive cells are small amacrine neurons, located either in the inner nuclear layer or in the ganglion-cell layer. They send processes mainly to the middle sublayer and to a lesser extent to the outermost sublayer of the inner plexiform layer. They resemble the small TH-positive bouquet cells described previously. In order to ascertain the relationship between PNMT-positive cells and TH-positive bouquet cells, a double immunohistochemical labeling technique, using anti-TH and anti-PNMT antisera, has been developed on semi-thin sections. The result of these experiments clearly indicate that the populations of TH positive cells and PNMT-positive (presumably epinephrinergic) cells are separated. The absence of TH enzyme in the PNMT-positive cells raises the question of the enzymatic activity of PNMT, which appears to be different from the classical pathway of catecholamine biosynthesis in the retina. PMID- 2878822 TI - Target organ destruction enhances recovery of choline acetyltransferase activity in adult rat sympathetic ganglia after denervation. AB - We studied the effect of destruction of the adrenergic neuronal population on the recovery of preganglionic choline acetyltransferase activity in adult rat sympathetic ganglia. To produce a partial destruction of the adrenergic system, rats were injected with guanethidine for 4 weeks; the preganglionic nerve to the superior cervical ganglion was then crushed and the guanethidine injections were continued for an additional 3 days to 6 weeks. To determine that the drug was effective, tyrosine hydroxylase activity was assessed; enzymic activity was reduced by 76% or more after guanethidine administration. In addition, electron microscopy studies showed that the number of principal cell-synaptic contacts and vesicle-containing varicosities were decreased by 90% after guanethidine administration. Those measures indicated the drug effectively destroyed the postsynaptic adrenergic neurons. In contrast, crushing the preganglionic nerve in animals not treated with guanethidine did not change tyrosine hydroxylase activity, suggesting minimal nonspecific damage to the ganglion as a result of the lesion. Choline acetyltransferase activity was measured as an index of presynaptic cholinergic integrity. After crush of the preganglionic nerve, there was a gradual recovery of ganglionic choline acetyltransferase activity in the saline-injected rats from 5% of control 3 days after the crush to 49% of control after 6 weeks. On the other hand, in the ganglia of rats administered guanethidine, there was a much enhanced recovery of choline acetyltransferase activity after the nerve crush compared with saline-injected animals; in the guanethidine-injected rats, the ganglionic choline acetyltransferase activity 3 days and 6 weeks after the nerve crush was 15 and 96%, respectively, compared with the uncrushed side. These results demonstrate after destruction of the adrenergic target tissue, recovery of presynaptic choline acetyltransferase activity in the adult rat sympathetic ganglion can still occur after denervation; however, the mechanism(s) that controls the regeneration is altered, so that enzymic activity is enhanced. PMID- 2878823 TI - Population growth and economic development: two new U.S. perspectives. PMID- 2878824 TI - Synthesis and pharmacological evaluation of cyclic and opened thioanalogues of piperoxan. AB - Three piperoxan analogues, derived from the opening of the benzodioxane ring and/or replacement of the oxygen atom with the less polar sulfur, were synthesized. The decrease of the alpha-blocking activity found for these compounds showed that the binding site of benzodioxane-like compounds does not accept the substitution with less polar groups. PMID- 2878825 TI - Transport of F1-ATPase subunit beta into mitochondria depends on both a membrane potential and nucleoside triphosphates. AB - Transport of cytoplasmically synthesized precursor proteins into or across the inner mitochondrial membrane requires a mitochondrial membrane potential. We have studied whether additional energy sources are also necessary for protein translocation. Reticulocyte lysate (containing radiolabelled precursor proteins) and mitochondria were depleted of ATP by pre-incubation with apyrase. A membrane potential was then established by the addition of substrates of the electron transport chain. Oligomycin was included to prevent dissipation of delta psi by the action of the F0F1-ATPase. Under these conditions, import of subunit beta of F1-ATPase (F1 beta) was inhibited. Addition of ATP or GTP restored import. When the membrane potential was destroyed, however, the import of F1 beta was completely inhibited even in the presence of ATP. We therefore conclude that the import of F1 beta depends on both nucleoside triphosphates and a membrane potential. PMID- 2878826 TI - Characterization of nucleotide-binding sites on the chloroplast coupling factor 1 using two photolabile analogs. AB - Nucleotide-binding sites on the chloroplast coupling factor 1 (CF1) have been probed using two photoreactive ADP analogs: 2-azido-ADP (2-N3-ADP) and 2',3'-O-(4 benzoyl)benzoyl-ADP (Bz-ADP). Photolabeling of the isolated CF1 with 2-N3-ADP results in incorporation of the analog exclusively into the beta-subunit of the enzyme. The location of the nucleotide-binding site(s) within the beta-subunit of the CF1 was investigated using peptide mapping. Within the discrimination limits of this technique, it is concluded that the azido- and benzoyl-modified analogs both bind to the same conformation of the nucleotide-binding site(s) of soluble CF1. Bz-ADP, however, labels the binding site(s) on membrane-bound CF1 in a slightly different manner. PMID- 2878827 TI - Regulation of ATP hydrolase activity of the F0-F1 complex of rat-liver mitochondria during early hepatic regeneration. AB - Submitochondrial particles prepared from rat liver in the early phase of hepatic regeneration possess a reduced F1 content with respect to F0 in intact F0F1-H+ ATPase complexes. Analysis of ATP hydrolysis showed a significant difference in both ESMP and isolated F1 with regard to the higher affinity Km values (Km,1) obtained from Eadie-Hofstee plots. Both ESMP and F1 from regenerating rat liver showed much lower apparent Km,1 values (0.04 and 0.03 mM, respectively) than the corresponding controls (0.08 mM for both ESMP and F1). Data presented here show that the residual F1 moieties have an altered kinetic pattern with regard to the competitive inhibitor adenosine 5'-[beta,gamma-imido]triphosphate (K1 ESMP from regenerating rat liver = 0.67 microM, K1 ESMP from control rat liver = 2.03 microM). This difference in affinity for [beta,gamma-imido]-ATP is also seen in isolated F1 (K1 regenerating rat liver = 0.04 microM, K1 control rat liver = 0.22 microM). These data indicate that during the disruptive retrodifferential phase of hepatic regeneration, changes at the level of surviving F1 sectors of the F0 F1 ATPase may play a physiological role in preventing ATP hydrolysis in vivo in the brief period of low delta microH+, induced by the presence of non-F1 associated F0 proton-conducting pathways. PMID- 2878828 TI - Isolation of a cDNA for the rat heavy neurofilament polypeptide (NF-H). AB - We have isolated from a rat brain lambda gt11 expression library two overlapping cDNA clones of sizes 2.5 and 3.0 kb corresponding to the heavy neurofilament polypeptide (NF-H). The 2.5 kb insert apparently represents virtually the whole of the C-terminal tail, the 3.0 kb insert also encodes the conserved epitope for the monoclonal antibody, anti-IFA. The identity of the cDNAs was established by comparison of the predicted amino acid sequence with the known partial amino acid sequence of porcine NF-H. A repeat peptide sequence that may be a multiphosphorylation site was identified in the C-terminal non-helical tail. PMID- 2878829 TI - [Assessment of the activities of the medical personnel in feldsher-midwife centers]. PMID- 2878830 TI - [Prevention of dental diseases at a feldsher-midwife center]. PMID- 2878831 TI - [In vitro study of the diffusion of metronidazole (Klion) in extracted teeth]. PMID- 2878832 TI - Worldwide nursing: commonalities and differences. PMID- 2878833 TI - The impact of early medical technology on maternal mortality in late 19th century Sweden. AB - The prevention of fatal complications of childbirth is a priority of health care in the developing countries. This historical study of maternal deaths in Sweden analyses the decline in mortality between 1751-1900 and during this years maternal mortality was reduced by 76% whereas the female mortality dropped only by 33% The decline was especially pronounced during the period 1861-1900, when maternal mortality declined from 567 to 227 per 100,000 live births. The potential impact of medical technology was analysed by epidemiological methods for the period 1861-1900. The introduction of antiseptic technique was estimated to reduce septic maternal mortality 25-fold in lying-in hospitals and 2.7-fold in rural home deliveries, implying that 49% of the septic maternal deaths were thus "prevented". In addition, licensed midwives assisting at home deliveries were estimated to reduce non-septic mortality 5-fold, thus "preventing" 46% of the non septic maternal deaths. This could be one explanation why Sweden had a lower maternal mortality than the U.S. and the U.K. in the beginning of the 20th century. PMID- 2878834 TI - Severe hypoglycemia during pregnancy: its frequency and predisposing factors in diabetic women. AB - Severe hypoglycemic episodes, as defined as altered consciousness to the extent that self treatment is impossible, were sought prospectively in pregnant diabetic women. One or more episodes were found in none of 21 gestational onset, insulin requiring women during their 28 pregnancies but were present in 19 (33%) of the 57 already insulin dependent (Type 1) women during 26 (36%) of their 72 pregnancies. The most common predisposing factors included strict glucose control, anorexia, early morning hours (1200-0900), lack of an adrenergic response and time shortly before the next anticipated meal. PMID- 2878835 TI - Fetal heart monitoring and ultrasound in the management of placental abruption. AB - Three cases of placental abruption with the "pseudosinusoidal" fetal heart rate (FHR) pattern, a periodic late deceleration related to frequent uterine contractions are reported. This 'pseudosinusoidal' pattern is clearly not a true sinusoidal pattern. The fetal monitoring patterns of these patients are presented and discussed along with the use of ultrasound in the management of this condition. All infants were delivered by cesarean section with low Apgar scores at birth, but they soon recovered completely. PMID- 2878836 TI - Mortality associated with sterilization: preliminary results of an international collaborative observational study. AB - Sterilization is the contraceptive method most widely used worldwide, yet the case-fatality rate of deaths attributable to sterilization is not known. We used data collected from 1971-1979 from 28 countries by Family Health International to estimate case-fatality rates. We adjusted these rates for individuals lost to follow-up. Of 41,834 sterilizations, 23 resulted in deaths temporally associated with the procedure used. The adjusted attributable case-fatality rates were 13.4 per 100,000 for interval procedures, 53.3 per 100,000 for postabortion procedures, and 43.4 per 100,000 sterilizations after vaginal delivery. Multiple factors contributed to the deaths, including pre-existing health problems, infection and anesthesia. Prevention of deaths resulting from sterilization depends on complete ascertainment of deaths associated with sterilization and careful investigation to determine preventable risk factors. We conclude that, overall, sterilization in these programs was conducted with very low attributable mortality. PMID- 2878837 TI - Preliminary experiment with computerized anamnesis in gynecology and reproductive health. AB - The Hospital of the Faculty of Medical Sciences of the State University of Campinas is implementing an Integrated Health Care Programme, whose objectives are early detection of risk factors of several diseases and the evaluation of the patient's reproductive health at the moment of the first visit to the Hospital. The initial results of this program encouraged us to try to apply it all to our own clientele. The present lack of material resources and qualified manpower leads us to concentrate all our attention on the patient's immediate complaints. This situation indicated to us that the only way to implement the program should be by means of a computerized questionnaire able to detect diseases and risk factors early. This paper presents the preliminary results of the application of computerized questionnaires to evaluate health risks. The authors conclude: The application of a computerized questionnaire met with very favorable reception by the clientele; In some segments of the population, the questionnaire can be answered by the patients in direct interaction with the computer; Programmes which evaluate risk factors need to be carefully revised before being put to use; The system operates on a relatively low cost basis, which could bring undeniable benefits to primary health care. PMID- 2878838 TI - Metabolic effects of depot-medroxyprogesterone acetate in long-term users: a cross-sectional study. AB - Oral glucose tolerance test and determination of insulin, cholesterol, triglycerides, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase and cortisol in blood were performed on 57 Thai women who had used depot-medroxyprogesterone acetate (DMPA) for 5 years or more and 24 healthy non-DMPA users. Plasma insulin, alkaline phosphatase and morning cortisol levels were significantly higher in the DMPA users than in the non-users. There were no significant differences for other laboratory tests. The findings suggest some effects of DMPA on carbohydrate metabolism and liver function in long-term users. PMID- 2878840 TI - Expression of HLA class I and class II antigens in human choriocarcinoma cell lines. AB - Eight choriocarcinoma cell lines (6:gestational origin, 2:non-gestational origin) were studied by a radioimmune inhibition test using monoclonal antibodies for the expression of HLA class I and class II antigens. Levels of HLA class I antigens were very slight or nil. On the other hand, no HLA class II antigen was detected in any choriocarcinoma cell lines examined. PMID- 2878839 TI - Ripening of the cervix with prostaglandin E2-gel. A randomized study with a new ready-to-use compound of triacetin-prostaglandin-E2-gel. AB - A randomized study with a group of patients treated with a new ready-to-use triacetin-prostaglandin E2-gel compared to a non-treated group was conducted. The gel-treated group showed a distinct difference in cervical score after 12 h and ten patients were delivered during this period without further induction attempt compared to none in the control group. There was a significantly lower need for oxytocin stimulation in the treated group (P less than 0.0005), but there was no difference in the cesarean section rate or instrumental delivery rate. No side effects were seen. This new gel seems effective and safe. PMID- 2878841 TI - Perinatal factors in twin mortality in Nigeria. AB - The results of a retrospective study involving 622 twin-pairs born over an 18 month period among 17,726 births at the University of Ilorin Teaching Hospital, Ilorin, Nigeria, are presented with particular reference to four variables: birthweight, presentation, parity, and intertwin delivery time interval. The twinning incidence was 35.1 per 1000. Monozygous and dizygous rates are 7 and 28 per 1000, respectively. Overall perinatal mortality (PNM) was 15.5%. Mortality was higher in second than in first twin (19.5% vs. 11.6%), and consistently higher when divided into birthweight groups. Corrected PNM increased with breech presentations: 16.3% in breech:breech compared with 3.9% in vertex:vertex presentations. The twinning rate increased with parity; PNM is low in parity 1, of little variation in birth-ranks 2-5, and high in para 6 and above. Delivery of the second twin within 15 min seems optimal, giving a corrected PNM 3.6% in contrast to rates of 10.1%, 14.0% and 19.1%, respectively when delivery occurred between 16 and 30, 31 and 60 and greater than 60 min, respectively. Prevention of preterm delivery, increased use of cesarean section delivery for malpresentation, active management of delivery of second twin within an optimal time of 15 min, and family planning are suggested in order to decrease twin PNM. PMID- 2878842 TI - Continuous extraovular prostaglandin F2 alpha instillation for late pregnancy termination in patients with previous cesarean section delivery. AB - Late pregnancy termination by continuous extraovular instillation of prostaglandin F2 alpha (PGF2 alpha) was successfully performed in 13 patients with previous cesarean section (CS) delivery. The indications for pregnancy termination were intrauterine fetal demise in nine patients, social indications in two patients. Down's Syndrome in one patient and quadruplets pregnancy in one patient. One patient had a previous classical vertical cesarean section, two had two previous and one three previous low segment transverse (LST) cesarean sections. The other nine patients had one previous low segment transverse cesarean section. The instillation of prostaglandin solution was obtained by using a new double balloon catheter designed for extraovular pregnancy terminations. All patients aborted following the procedure with no complications. The instillation abortion time ranged from 5 1/2 to 20 h (mean 13.3 h). PMID- 2878843 TI - Non-vascular transplantation of the rabbit uterus. AB - Transplantation of the uterus may be an optimal solution in young hysterectomized patients, in women with agenesis of the uterus or in severe uterine anomalies. In the human model, attempted tubal and ovarian homografts have usually failed. Eighteen rabbits underwent unilateral non-vascular uterine transplantation. Four rabbits underwent total unilateral uterine autograft. Three uteri showed severe inflammation and necrosis 72 h, 1 week and 1 month postoperatively. Thereafter, the operative technique was modified to avoid contamination from the vagina and four rabbits underwent supravaginal unilateral non-vascular autograft. Three uteri had preserved endometrial and myometrial structure on relaparotomy. The following four rabbits underwent homotransplantation of the uterus and showed acute rejection of the transplant. Under cyclosporine therapy three homotransplanted rabbits developed pelvic abscesses while three other rabbits showed preserved myometrial and endometrial structures. PMID- 2878844 TI - The ontogeny and maintenance of adult symmetry properties in the ctenophore, Mnemiopsis mccradyi. AB - Ctenophores are biradially symmetrical animals. The body is composed of four identical quadrants which are organized along an oral-aboral axis. Most species have eight comb rows, two tentacles, and an apical organ (located on the aboral surface). During embryogenesis there is a fixed pattern of cleavage, a precocious specification of blastomere developmental potential, and an inability to regulate for portions of the embryo that have been removed. When blastomeres are separated at the two-cell stage each blastomere develops into a "half-animal" with four comb rows, one tentacle, and half an apical organ. In contrast, adult ctenophores regenerate readily. When an adult ctenophore is cut in half to produce "half animals," in most cases each half regenerates the missing half. In some cases, however, bisected animals remain as "half-animals" which repair the wound site but do not replace all of the missing structures. When animals are cut in half along the tentacular or esophageal axis at different stages of embryogenesis a transition period is detected when the capacity for adult regeneration begins. This transition occurs at the time when the formation of the apical organ is complete and comb row function becomes coordinated. Embryos bisected prior to this time remain as "half-animals" even after growing to large reproductive sizes, while animals bisected after the transition period usually regenerate the missing structures within 2-3 days. When adult "half-animals" (produced by bisection either before or after the transition period) are cut into "quarter pieces," the pieces regenerate to form either "half-animals" or whole animals. Thus, "half-animals" produced prior to the transition period--although they failed to undergo embryonic regulation--have not irreversibly lost the capacity to form whole animals if challenged to regenerate during adult stages. When aboral blastomeres destined to form the apical organ, tentacles, and comb rows are removed from early cleavage stages (prior to the transition period), the embryo does not form these structures at the appropriate time. However, the resulting deficient adults spontaneously form these structures from remaining blastomere lineages soon after hatching. These experiments suggest that as long as some quadrant-specific cells of the oral pole are present at the time of the transition period, the structures of that quadrant will be spontaneously replaced during the adult period.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2878845 TI - The titration of clostridial toxoids and antisera in cell culture. AB - The practicability of cell culture titration methods for antigens and antitoxins derived from Clostridium perfringens, Cl. septicum and Cl. novyi was investigated. Toxin neutralization could not be demonstrated with Cl. perfringens filtrates but assays for antitoxin based on the use of cultures of Vero cells were practicable for Cl. novyi and Cl. septicum. In the case of the latter, the precision and reproducibility of the test was sufficient for quality control purposes. PMID- 2878846 TI - A mouse model to estimate the potency of the diphtheria component in combined vaccines. AB - A mouse model is presented to estimate the potency of the diphtheria component in combined vaccines. In addition, a simplified mouse test is suggested for routine potency control of diphtheria. It will be important to discuss this approach to replace the lethal challenge test in guinea pigs. PMID- 2878847 TI - An enzyme immunoassay for measuring Escherichia coli pilus antigens. AB - Quantitative enzyme-linked antibody centrifuge (ELAC) assays have been developed for measuring Escherichia coli adhesion pilus antigens K99, K88, 987P and F41 in E. coli bacterins used for protecting newborn animals against neonatal enteric colibacillosis. The test consists of reacting an alkaline phosphatase conjugate of specific pilus antigen antibody directly with dilutions of the bacterin on test and a standard reference bacterin. Following incubation the unbound conjugate is removed by two centrifugation steps and the bacteria with bound conjugate are reacted with substrate. The optical density is measured at 405 nm. Unknown samples are compared to a standard bacterin known to develop sufficient immunity in sows to provide protective levels of passive maternal immunity to their piglets. A relative potency (RP) value is calculated and used for standardizing bacterial concentrates and for final potency testing. The advantages to be realized are: shortening of the test period, specificity, and reduction in test animal usage. PMID- 2878848 TI - Somatostatin does not increase insulin-stimulated glucose uptake in humans. AB - Somatostatin (SRIF) has been widely used in the study of in vivo carbohydrate metabolism to suppress pancreatic hormone secretion and thereby interrupt the glucoregulatory feedback loops between insulin, glucagon, and glucose. A critical assumption in the use of SRIF is that it has no effect on hepatic or peripheral glucose metabolism other than those mediated through the inhibition of hormone secretion. To assess whether doses of SRIF commonly used in human investigation have any effect on insulin-stimulated glucose disposal rates, we measured the rate in 6 normal subjects (mean fasting serum glucose level, 93 +/- 2 mg/dl) during euglycemic (approximately equal to 85 mg/dl) hyperinsulinemic (40 mU X m-2 X min-1) clamp studies both with and without the concomitant infusion of SRIF (600 micrograms/hr). The steady-state insulin levels achieved were 85 +/- 6 microU/ml and 74 +/- 8 microU/ml with and without SRIF, respectively (difference not significant). Glucose disposal rates between 120 and 180 min of the clamp were 7.11 +/- 0.10 and 7.35 +/- 0.10 mg X kg-1 X min-1 with and without SRIF, respectively (difference not significant). We concluded that in doses commonly used in human investigation, SRIF does not increase glucose disposal. PMID- 2878849 TI - Patterns of DNA distribution and neurohormone immunoreactivity in the tumour cells: tools for the histopathological assessment of gastro-intestinal carcinoids. AB - Modern immunohistochemical and DNA cytochemical analyses of gastro-intestinal carcinoids have yielded results that have increased our knowledge of the biological properties and the histogenesis of these theoretically and practically so fascinating kinds of neoplasm. Carcinoids in different anatomical localisations were found to show marked differences with regard to their neurohormone peptide immunoreactivity pattern and their ability to evoke clinical signs and symptoms of hormone overproduction. This can be of great help to the practising pathologist when he tries to predict the anatomical site of an unknown primary tumour from the results of this histopathological assessment of a metastatic nodule of a carcinoid. The DNA distribution pattern in the nuclei of carcinoid tumour cells is a tool in the histopathological assessment of the neoplasm that seems to be of some value in predicting the subsequent clinical course of the disease. This conclusion is based on the results of a pilot study of 8 cases of ileal carcinoids with liver and lymph node metastases. It was found that 4 cases with a rapidly progressive fatal disease had a higher proportion on non-diploid tumour cell nuclei than 4 cases still alive and at full work 5 years after the diagnosis of liver metastases. However, the number of aneuploid tumour cell nuclei was negligible in both groups. PMID- 2878850 TI - Restriction fragment length polymorphism (RFLP) of the human insulin receptor gene in Japanese: its possible usefulness as a genetic marker. AB - Restriction fragment length polymorphism of the human insulin receptor gene was analyzed with a 4.2 Kb cDNA probe in Japanese normal subjects and Type 2 (non insulin-dependent) diabetic patients. Restriction endonuclease Rsa I digestion showed polymorphism of the human insulin receptor gene, with a band at 6.7 Kb, 6.2 Kb or 3.6 Kb. The frequency of the 6.7 Kb band was less than that in Caucasians. Furthermore, 15% of all the Japanese subjects examined lacked a 3.6 Kb band, which is commonly found in Caucasians. We have also detected restriction fragment length polymorphism in the human insulin receptor gene by Pvu II or Stu I digestion. Although no significant association of restriction fragment length polymorphism with Type 2 diabetes was found in the present study, our results suggest that the restriction fragment length polymorphism in the human insulin receptor gene varies among ethnic groups, and that the restriction fragment length polymorphism linked to the human insulin receptor gene might be a useful marker for the linkage study of the genes located close to the human insulin receptor gene on chromosome 19. PMID- 2878851 TI - Developmental regulation of the pathways of folate-receptor-mediated stimulation of cAMP and cGMP synthesis in Dictyostelium discoideum. AB - Recently, we demonstrated the presence of multiple folate-binding sites on the cell surface of Dictyostelium discoideum. These sites were divided into two major classes, with different ligand specificities (A and B). Each major class consists of several interconvertible subtypes. In the present report, the ability of 13 folate analogs to activate both adenylate and guanylate cyclase in pre- as well as postaggregative cells is examined. The patterns of correlation between binding and activation data indicate that guanylate cyclase activation is mediated by the B-sites in both developmental stages (P less than 0.001). In postaggregative cells, adenylate cyclase also seems to be activated by the B-sites (P less than 0.001). In contrast, adenylate cyclase activation in preaggregative cells was well correlated with the specificity of A-sites (P less than 0.01). Remarkably, the potencies of activation were less affected by molecular modifications than the binding affinities were, as suggested by a slope of 0.4 in a plot of K0.5 values of activation vs. binding. This observation argues against the existence of a transduction mechanism in which the response is proportional to receptor occupancy. For the B-receptor, however, the degree of receptor occupancy appears to determine the response. The existence of folic acid antagonists is demonstrated, some of which are specific for either A-sites coupled to adenylate cyclase or for B-sites coupled to guanylate cyclase. PMID- 2878852 TI - [Bile secretion in pregnancy]. PMID- 2878853 TI - [New intracellular messengers for the action of hormones, neurotransmitters and several peptides in the digestive tract]. PMID- 2878854 TI - [Hemorrhagic fever with renal syndrome: a case with jaundice]. PMID- 2878855 TI - [Efficacy of adenine arabinoside (vidarabine) in the treatment of periarteritis nodosa associated with chronic active viral hepatitis B]. PMID- 2878856 TI - Influence of chronic drug-induced achlorhydria by substituted benzimidazoles on the endocrine stomach in rats. AB - The release of gastric somatostatinlike immunoreactivity and gastrin was studied in rats with chronic achlorhydria induced by the substituted benzimidazole BY 308. In vitro, stimulation of gastrin release by acetylcholine was slightly enhanced after 1 day of treatment but no further effects were observed compared to placebo controls. Four weeks of treatment evoked marked gastrin hypersecretion, which was atropine-resistant. Stimulation of gastrin release was inversely correlated to enhancement of basal gastrin levels. Chronic achlorhydria distinctly reduced somatostatin responses to isoproterenol, whereas potent stimulation was observed in controls. Treatment with BY 308 for 1 wk was associated with fully developed gastrin hypersecretion but isoproterenol stimulated somatostatin release was still unaffected. Hypergastrinemia accompanied by increased antral gastrin and reduced antral and fundic somatostatin concentrations was also found in vivo after 4 wk of treatment with BY 308. It is concluded that chronic achlorhydria not only enhances storage and secretion of gastrin but also diminishes the secretion and tissue stores of somatostatin; adaptive changes of the somatostatin cell occur, however, with a much longer delay. PMID- 2878857 TI - Escape of the response to a long-acting somatostatin analogue (SMS 201-995) in patients with VIPoma. AB - Two patients with severe secretory diarrhea due to metastatic vasoactive intestinal peptidoma were treated with a synthetic somatostatin analogue in an attempt to control the patients' vasoactive intestinal peptide-related symptoms. In both patients, a good initial response to this treatment could be demonstrated; not only did diarrhea subside but there was also a dramatic fall in vasoactive intestinal peptide plasma levels. However, after 11 and 4 days respectively, diarrhea recurred accompanied by a rise in vasoactive intestinal peptide plasma levels. In fact, under treatment with the somatostatin analogue and with natural somatostatin, a significant rebound state was observed regarding diarrhea as well as vasoactive intestinal peptide levels, which caused considerable difficulty in the clinical management in 1 patient. This patient had to undergo surgery. In the second patient, the responsiveness to somatostatin analogue returned a few days after discontinuation of the treatment, lasting, however, for a short period only. The possible mechanism of this escape and rebound with somatostatin treatment is discussed. PMID- 2878858 TI - [New knowledge about the endocrine regulatory system]. PMID- 2878859 TI - Effect of azodisal sodium and sulphasalazine on ileostomy output of fluid and PGE2 and PGF2 alpha in subjects with a permanent ileostomy. AB - Azodisal sodium is a highly effective means of oral delivery of 5-amino-salicylic acid to the colonic mucosa. Administration of this drug to patients intolerant of sulphasalazine, however, occasionally results in liquid stools. In preliminary experiments, which comprised 10 healthy volunteers treated with colectomy for ulcerative colitis, ileostomy fluid output increased (p less than 0.001) during oral intake of azodisal sodium (1 g/day). In a double blind, placebo controlled crossover study, comprising eight similar volunteers, ileostomy fluid output increased (p less than 0.05) in a dose related manner during intake of azodisal sodium (1 g/day vs 2 g/day) compared with placebo or sulphasalazine (2 g/day). Concentrations of prostaglandin (PG)F2 alpha in free ileal water determined by equilibrium in vivo dialysis of ileostomy contents decreased (p less than 0.05) during intake of azodisal sodium (2 g/day), whereas concentrations of PGE2 and the output of PGE2, PGF2 alpha, and 'PGE2 + PGF2 alpha' remained unchanged. Thus increased formation of PGs is apparently not the cause of increased ileostomy fluid output associated with azodisalicylate intake. PMID- 2878860 TI - Changes in the gastric mucosa of the mouse associated with long lasting unsurmountable histamine H2 blockade. AB - The oral administration of loxtidine to mice at doses of 600, 250, and 50 mg/kg/day for 746 days produced carcinoid tumours of the gastric fundus. The fundic mucosa also showed marked atypical hyperplasia with changes in foveolar cells similar to those seen in early incomplete metaplasia. These effects may be related to the prolonged achlorhydria produced by this potent unsurmountable histamine H2 receptor antagonist. PMID- 2878861 TI - [A study on the renal action of beta 1- and beta 2-adrenoceptors in rats]. AB - The present experiments were designed to study urine volume and urinary sodium excretion effects of beta-antagonists and beta-agonists with reference to beta 1- and beta 2-adrenoceptors in rats. The beta-antagonists used were atenolol as a selective beta 1-antagonist, butoxamine as a beta 2-antagonist and propranolol as a non-selective beta-antagonist. The beta-agonist used were salbutamol as a beta 2-agonist and isoproterenol as a non-selective beta-agonist. Beta-antagonists increased the urine volume and urinary sodium excretion, but beta-agonists decreased the urine volume and urinary sodium excretion. With regards to these effects, atenolol increased the urine volume more than urinary sodium excretion, isoproterenol decreased the urine volume more than urinary sodium excretion, and salbutamol decreased the urinary sodium excretion more than urine volume. When beta-antagonists were infused with a beta-agonist, the original diuretic effects of these beta-antagonists were inhibited by the beta-agonist. In these effects, beta-antagonists infused with isoproterenol inhibited urine volume more than urinary sodium excretion, but beta-antagonists infused with salbutamol inhibited urinary sodium excretion more than urine volume. These results indicate that the urine volume is related to beta 1-adrenoceptors, while the urinary sodium excretion is related to beta 2-adrenoceptors, although there is no selectivity towards either beta 1-adrenoceptors or beta 2-adrenoceptors as far as diuresis or antidiuresis is concerned. PMID- 2878862 TI - [Long-term treatment of wide-angle glaucoma with the beta blocker levomoprolol: therapeutic effectiveness without side effects]. PMID- 2878864 TI - [Security through experience. 4 decades of corticoid therapy]. PMID- 2878863 TI - [Effect of various beta blockers on intraocular pressure and ventilation]. PMID- 2878865 TI - Effect of adrenalectomy on the pancreas of db/db mice. AB - Adrenalectomy has been performed in the diabetic mouse and the islet immunohistochemistry studied. Adrenalectomy restored blood glucose to normal. Mean islet size of diabetic animals was larger than that of either adrenalectomized diabetic animals or of lean controls. Adrenalectomy restored the immunohistochemical appearance of the islets to normal when examined with anti insulin, anti-glucagon and anti-somatostatin antisera. PMID- 2878866 TI - Improvement of diabetes after treatment with somatostatin analogue SMS 201-995 in an acromegalic patient. AB - The beneficial effects of long acting somatostatin analogue SMS 201-995 in an acromegalic patient affected by severe diabetes mellitus are reported. Neither human insulin alone nor human insulin plus bromocriptine allowed satisfactory metabolic control though, with the latter treatment, virtually normal plasma GH levels were reached. Conversely, addition of SMS 201-995 to insulin treatment led to normalization of blood glucose. This result was obtained with a dose of SMS 201-995 of 400 micrograms/day and only after 3 weeks of therapy. PMID- 2878867 TI - Portal venous flow in response to acute beta-blocker and vasodilatatory treatment in patients with liver cirrhosis. AB - The drugs currently under investigation in the prevention of recurrent gastrointestinal bleeding in cirrhosis are likely to decrease the portal pressure by means of a primary reduction of portal blood flow. The hemodynamic effects of beta-blocking agents and vasodilatory drugs were noninvasively measured in eight patients with cirrhosis by means of pulsed echo-doppler equipment. Portal caliber, blood velocity and flow were recorded hourly after a single dose of propranolol (40 mg p.o.) or atenolol (100 mg p.o.), and every 5 min after treatment with isosorbide dinitrate (5 mg sublingually). The drugs were administered at random with an interval of 2 days or more. The portal caliber decreased after atenolol, but did not change after propranolol and isosorbide. The blood velocity decreased by 29 +/- 2% 3 hr after propranolol, by 26 +/- 2% 3 hr after atenolol and by 31 +/- 3% 15 min after isosorbide. The portal blood flow decreased by 0.29 +/- 0.03 liters per min after propranolol, by 0.34 +/- 0.06 after atenolol and by 0.26 +/- 0.03 after isosorbide, without any difference among the various treatments. beta-blockers and vasodilatory drugs have comparable effects on portal blood flow. beta 1-selective and nonselective beta blockers are similarly effective in keeping with the hypothesis that changes in portal blood flow are mainly due to the block of beta 1-receptors. PMID- 2878869 TI - Associations between restriction fragment length polymorphisms detected with a probe for human 21-hydroxylase (21-OH) and two clinical forms of 21-OH deficiency. AB - DNAs from unrelated healthy individuals and unrelated individuals affected with 21-hydroxylase deficiency (congenital and late-onset adrenal hyperplasia) were digested with seven restriction enzymes and hybridized with a cDNA probe specific for human 21-hydroxylase genes. Associations were found between restriction fragments and the two forms of the disease: The late onset form is associated with a double dose of a 14 kb fragment generated by EcoRI and with a triple dose of a 3.2 kb fragment generated by Taq I in patients with HLA B14 haplotypes; The classical congenital form is negatively associated with the 14 kb fragment and with a 3.7 kb fragment generated by Taq I in patients with HLA Bw47 haplotypes. A 3.2 kb Taq I fragment is negatively associated with the HLA B8 haplotypes. The other five enzymes tested give no polymorphisms or polymorphisms without correlation with the two forms of the disease. PMID- 2878868 TI - Localisation of the gene for Hunter syndrome on the long arm of X chromosome. AB - The localisation of the gene for Hunter syndrome (MPS II) has been studied in 11 families using 12 polymorphic DNA markers, one on the short arm and the remaining 11 located at various points on the long arm of the X chromosome. Lod scores for seven probes were uniformly negative for all values of theta; positive scores at values of theta = 0.10 or more were obtained for the five probes located most distally on the long arm (52A, F9C, DX13, St14-1, F8C). Current data suggest the most likely order of the loci to be: 52A, F9C, Hunter, DX13, St14-1, F8C-qter; the Hunter locus may thus be close to that for the fragile site at Xq27. PMID- 2878870 TI - A highly polymorphic locus on chromosome 16q revealed by a probe from a chromosome-specific cosmid library. AB - A cosmid library was constructed from genomic DNA of a human-mouse somatic cell hybrid containing an 11q-16q translocation chromosome as the only human DNA. Cosmids with human inserts were prehybridized with total human DNA and were screened to find probes that revealed highly polymorphic loci. From one such cosmid, CF33-79, a single-copy subclone was isolated which revealed an insertion/deletion polymorphism with at least 11 alleles and a PIC of 0.77. Using a somatic cell hybrid mapping panel, the subclone was mapped to chromosome 16. By in situ hybridization with the entire cosmid used as a probe, chromosomal localization was shown at 16q22----24. PMID- 2878871 TI - Alpha-thalassemia in Papua New Guinea. AB - A study of the distribution of alpha-thalassemia in Papua New Guinea (PNG) was carried out by DNA analysis. A total of 664 DNA samples were screened for alpha thalassemia 2 and alpha-thalassemia 1 caused respectively by either deletion of one or both of the duplicated alpha-globin genes. alpha-Thalassemia 2 was detected in high frequencies in coastal and lowland regions where malaria has been holo- to hyperendemic but in low frequencies in non-malarious highland regions. The highest frequency was observed in the north coast of PNG. The distribution of alpha-thalassemia 2 seems to be in accordance with other conditions such as ovalocytosis and G6PD deficiency which are also prevalent in this population, suggesting that they may interact in protection against malaria. However, it appears to be negatively correlated with beta-thalassemia and alpha thalassemia 1, the latter being extremely rare in this population. Analysis of the types and subtypes of the single alpha-globin gene deletion revealed a predominance of the -alpha 4.2 type in general, except in some regions in the south where the -alpha 3.7 type is prevalent. The -alpha 3.7 I subtype is the common form of the -alpha 3.7 deletion in the PNG mainland. The -alpha 3.7 III subtype, previously reported to be unique in Melanesians and Polynesians, was detected in an offshore island of PNG. However, this subtype is very rare in Melanesians from the PNG mainland. PMID- 2878873 TI - Origin of new mutations in Duchenne muscular dystrophy. AB - Nine unrelated pedigrees in which Duchenne muscular dystrophy (DMD) was not present in more than one sibship were studied, using 6 DNA polymorphisms closely linked to the DMD gene. The reconstruction of grandparental haplotypes indicates the occurrence of at least three new mutations, two in grandpaternal chromosomes and one in a grandmaternal chromosome. Two additional (but less well documented) new mutations might have occurred respectively in a grandfather's and in a grandmother's chromosome, the latter being represented by a deletion mutation. The new mutations detected in this study therefore add to a total of either three or five out of nine apparently independent mutations present in pedigrees without recurrence of the disorder. PMID- 2878874 TI - [Neurinomas of the lingual mucosa as markers of internal malignant pathology. A clinical case of type 2B multiple endocrine neoplasms]. PMID- 2878872 TI - Choroideremia: further evidence for assignment of the locus to Xq13-Xq21. AB - Choroideremia is an X-linked hereditary retinal dystrophy leading to blindness in early adulthood. RFLP analyses in three Danish families were consistent with close linkage between choroideremia and the locus DXYS1, located at Xq13-Xq21. Measurable linkage was found between choroideremia and DXS17, at Xq22. Furthermore, choroideremia was diagnosed in a boy with an interstitial deletion at Xq13-Xq21, strongly suggesting the assignment of the locus for choroideremia to this region of the X chromosome. The deletion also covered DXYS1, but did not include DXS17. PMID- 2878875 TI - Duodenal ulceration and the control of gastric acid secretion. PMID- 2878876 TI - Development of histamine H2-receptor antagonists and the pharmacology of ranitidine. PMID- 2878877 TI - Inaccuracy in the home use of automated blood pressure cuffs by hypertensive patients being treated with beta-blockers. PMID- 2878878 TI - Renal alpha 2-adrenergic receptors and hypertension. PMID- 2878879 TI - Role of renal alpha 2-adrenergic receptors in spontaneously hypertensive rats. AB - To identify a physiological role for renal alpha 2 adrenergic receptors, renal vascular and tubular responses to administration of graded frequencies of renal nerve stimulation or graded doses of adrenergic agonists were determined in anesthetized spontaneously hypertensive, Wistar-Kyoto, and Sprague-Dawley rats. Renal vasoconstrictor responses to renal nerve stimulation and alpha 1-adrenergic receptor agonists (norepinephrine, phenylephrine) were inhibited by an alpha 1 adrenergic receptor antagonist (prazosin) but not by an alpha 2-adrenergic receptor antagonist (rauwolscine). A semilog plot of renal vasoconstrictor responses a fraction of control renal blood flow versus agonist dose (in nanograms) was linear with the slope, k, taken as the fractional decrease in renal blood flow per nanogram. The alpha 2-adrenergic receptor agonists (clonidine, guanabenz) produced minimal renal vasoconstrictor responses (fractional decrease in renal blood flow per nanogram: norepinephrine, 0.011; phenylephrine, 0.003; clonidine, 0.00087; guanabenz, 0.000037). The small renal vasoconstrictor responses to clonidine and guanabenz were more inhibited by rauwolscine than by prazosin. Low frequency renal nerve stimulation produced antidiuresis and antinatriuresis without decreasing glomerular filtration rate or renal blood flow. The antidiuretic and antinatriuretic responses were inhibited by prazosin but unaffected by rauwolscine. The magnitude of the renal vascular and tubular responses and their adrenergic receptor mediation were not different between spontaneously hypertensive, Wistar-Kyoto, and Sprague-Dawley rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878880 TI - Role of sympathetic nervous system in hypotensive action of taurine in DOCA-salt rats. AB - We tested the hypothesis that the antihypertensive effects of dietary taurine supplementation in deoxycorticosterone acetate (DOCA)-salt rats may be attributed to the suppression of sympathetic nervous system activity. In uninephrectomized rats treated with DOCA while receiving 1% NaCl solution for 2 weeks, systolic blood pressure was significantly increased as compared with that in control rats treated with vehicle suspension and tap water. Sympathetic nervous system activity was assessed by tissue norepinephrine turnover, which was determined from the rate of decline of tissue norepinephrine concentration after the administration of alpha-methyl-p-tyrosine, a potent inhibitor of the rate limiting step of catecholamine synthesis. Cardiac and splenic norepinephrine turnover during either normal conditions or cold exposure (4 degrees C, 8 hours) were markedly increased in DOCA-salt rats as compared with control rats. Also, DOCA-salt rats had increased depressor response to hexamethonium bromide, a ganglion blocker. In contrast, supplementation of 1% taurine in DOCA-salt rats attenuated the development of the hypertension associated with the normalization of both the increased depressor response to ganglionic blockade and the accelerated cardiac and splenic norepinephrine turnover during either normal conditions or cold exposure. Taurine supplementation in control rats, however, had no effect on blood pressure or norepinephrine turnover during cold exposure. These results suggest that taurine supplementation suppresses sympathetic overactivity in DOCA-salt rats, thus leading to inhibition of the development of hypertension. PMID- 2878881 TI - Molecular basis for the pathological actions of Clostridium perfringens iota toxin. AB - Clostridium perfringens type E iota toxin is composed of two separate and independent polypeptide chains that act synergistically in mouse lethal assays. The light chain is an enzyme that mono(ADP-ribosyl)ates certain amino acids. The enzyme displays substantial activity when homopoly-L-arginine is used as a substrate, but it shows little activity when polyasparagine, polylysine or polyglutamic acid are used. In keeping with the properties of an ADP-ribosylating enzyme, the toxin possesses the following characteristics. It produces incorporation of radioactivity into polyarginine when adenine-labeled NAD is used, but radioactivity is not incorporated when nicotinamide-labeled NAD is used. Irrespective of labeling, enzymatic activity is accompanied by the release of free nicotinamide. After incorporation of ADP-ribose groups into polyarginine, enzymatic and chemical techniques can be used to release the incorporated material. Snake venom phosphodiesterase releases mainly AMP; hydroxylamine releases AMP and ADP-ribose. The heavy chain of iota toxin has little or no enzyme activity, and it does not substantially affect the enzyme activity of the light chain. The heavy chain may be a binding component that directs the toxin to vulnerable cells. The data suggest that iota toxin is a representative of a novel class of ADP-ribosylating toxins. PMID- 2878882 TI - Expression of Streptococcus sanguis antigens in Escherichia coli: cloning of a structural gene for adhesion fimbriae. AB - Chromosomal DNA from Streptococcus sanguis FW213 was partially digested with EcoRI and ligated into the positive-selection cloning vector pOP203(A2+). The ligation mixture was used to transform Escherichia coli K-12, and 4,500 transformants were examined. The tetracycline-resistant colonies had inserts averaging 3.2 kilobases. The entire colony bank was screened by colony immunoassay with polyclonal rabbit serum raised against S. sanguis FW213 whole cells. Thirty recombinant colonies produced stable positive reactions of various intensities, indicating that S. sanguis antigens could be expressed in E. coli. Restriction endonuclease digestion of these clones suggested that 26 of the clones were unique. Only two clones, VT616 and VT618, gave positive reactions with fimbria-specific antisera. That the gene coding for the antigen was located on the plasmid was confirmed by demonstrating that the presence of the plasmid was linked to antigen production. Western immunoblot analyses of sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels showed that both clones produced a fimbrial peptide of Mr 30,000. The two recombinant plasmids were shown by Southern analysis and restriction mapping to contain the same 6-kilobase EcoRI fragment inserted in opposite orientations. Southern hybridization confirmed that this fragment is present in S. sanguis genomic DNA. The Mr 30,000 protein gene was expressed in both orientations, suggesting that the fimbrial promoter is located on the 6-kilobase fragment. These results show that at least one streptococcal fimbrial gene can be cloned and expressed in E. coli. PMID- 2878883 TI - Bordetella pertussis adenylate cyclase: isolation and purification by calmodulin sepharose 4B chromatography. AB - Purified preparations of adenylate cyclase were obtained from crude urea extracts of Bordetella pertussis by a one-step calmodulin affinity chromatography technique. Diluted extract was loaded onto the column and washed, and adenylate cyclase was eluted with 10mM EGTA [ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid]. A 104-fold purification was accomplished in one step. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the affinity purified adenylate cyclase was dissociated into one major protein band with an apparent molecular weight of 60,000 and a minor band at 200,000. The affinity purified adenylate cyclase was observed to have adenylate cyclase enzymatic activity which was activated by calmodulin, to bind 125I-calmodulin, and to be free of pertussis toxin as determined by in vivo and in vitro assays. PMID- 2878885 TI - Cloning of the filamentous hemagglutinin of Bordetella pertussis and its expression in Escherichia coli. AB - Bordetella pertussis UT25 DNA was cloned into the kanamycin resistance gene of cosmid pCP13 to construct a genomic library in Escherichia coli LE392. One clone containing plasmid pDB441 expressed the filamentous hemagglutinin (FHA) as identified by protein immunoblots with the use of rabbit anti-B. pertussis antiserum, rabbit anti-FHA antiserum, and a monoclonal antibody to FHA. FHA is a protein of 220 to 210 kilodaltons, but the immunoreactive FHA, as expressed in E. coli, was larger than that expressed in B. pertussis, suggesting that there was a difference in the processing of this protein between these two bacteria. The fha gene was mapped to a 6.5-kilobase pair DNA fragment by the use of various restriction endonucleases. The kanamycin resistance gene of pCP13 was found to provide the promoter function but probably not the translation start signal for the fha gene. Conjugative transfer of pDB441 to B. pertussis BP353, a transposon Tn5-induced FHA mutant, increased the expression of the FHA over that seen with wild-type B. pertussis. PMID- 2878884 TI - Bordetella pertussis adenylate cyclase: effects of affinity-purified adenylate cyclase on human polymorphonuclear leukocyte functions. AB - Affinity-purified adenylate cyclase (AC) of Bordetella pertussis, free of contaminating pertussis toxin, was demonstrated to have biological effects on human polymorphonuclear leukocytes (PMN). AC at doses of 25 and 50 micrograms/ml increased intracellular cAMP levels in the phagocytes 7.6- to 23.5-fold, respectively, above basal levels. AC inhibited PMN chemiluminescence, chemotaxis, and superoxide production in a dose-dependent manner. The 50% inhibitory dose for chemotaxis and chemiluminescence was 36.5 micrograms/ml; for superoxide generation it was 71.0 micrograms/ml. Although these PMN metabolic functions were impaired, no effect on phagocytic activity was observed. PMID- 2878886 TI - A membrane-associated neuraminidase in Entamoeba histolytica trophozoites. AB - Trophozoites of the parasitic amoeba Entamoeba histolytica HM-1:IMSS possess a surface neuraminidase capable of liberating N-acetylneuraminic acid (NANA) from N acetylneuramin-lactose (alpha 2----3 or alpha 2----6) or mucin in their medium. The neuraminidase was found to be membrane associated, with more than 50% of the yield being recovered in the plasma membrane fraction. The neuraminidase specific activity of the plasma membrane fraction was six times that of internal membrane fraction enzyme. The optimum pH and temperature for this enzyme were 6.7 and 37 degrees C, respectively. Neuraminidase activity was inhibited by ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and the optimum Ca2+ concentration was 2 mM. The microfilament disruptor cytochalasin D (30 micrograms/ml) inhibited motility and neuraminidase activity of intact Entamoeba trophozoites. The cytochalasin D-induced loss of surface neuraminidase activity was explained in part by a redistribution of enzyme with a loss of plasma membrane enzyme and an increase in intracellular membrane enzyme. A qualitatively similar cytochalasin D effect was observed with two other membrane-associated enzymes, calcium-regulated ATPase and acid phosphatase. Membrane-associated enzyme was minimally affected by Triton X-100 and saponin. An N-acetylneuraminic acid aldolase, optimum pH, 7.4, was found in trophozoite homogenate supernatant fractions. NANA and NANA-containing compounds stimulated trophozoite-directed motility. This motility stimulation by NANA-containing compounds did not apparently require prior release of free NANA by the trophozoite surface neuraminidase. Entamoeba neuraminidase is one of a series of enzymes that may modify the mucus blanket and target cell surface and thereby play a role in the pathogenesis of amebiasis. PMID- 2878887 TI - Role of plasmid-encoded adherence factors in adhesion of enteropathogenic Escherichia coli to HEp-2 cells. AB - Plasmid-encoded adherence factors have been shown to be important for the full expression of enteropathogenic Escherichia coli (EPEC) pathogenicity and for EPEC adhesion to cultured HEp-2 cells. EPEC strain E2348 (O127) shows localized HEp-2 cell adhesion and possesses a 60-megadalton plasmid, pMAR2. When E2348 is cured of pMAR2 it loses the ability to adhere to HEp-2 cells, while nonadherent E. coli K-12 strains P678-54 and HB101 acquire HEp-2 adhesiveness after they gain the plasmid. By electron microscopy, E2348 was seen to adhere to HEp-2 cells in a manner that closely resembled EPEC adhesion to intestinal mucosa; bacteria were intimately attached to projections of the apical HEp-2 cell membrane and caused localized destruction of microvilli. The plasmid-containing K-12 strains, on the other hand, did not show intimate attachment and there was no modification of cell surface architecture. It is concluded that plasmid pMAR2 codes for an adhesin, possibly fimbrial in nature, that promotes HEp-2 adhesion but that other chromosomally encoded factors are required for EPEC to achieve the characteristic mode of intimate cell attachment. PMID- 2878888 TI - Identification of a new fimbrial structure in enterotoxigenic Escherichia coli (ETEC) serotype O148:H28 which adheres to human intestinal mucosa: a potentially new human ETEC colonization factor. AB - Three important fimbrial colonization factor antigens (CFAs) designated CFA/I, CFA/II, and E8775 were identified originally in some human enterotoxigenic Escherichia coli (ETEC) strains because of their mannose-resistant hemagglutination properties. To identify CFA, in strains lacking mannose resistant hemagglutination properties we exploited the ability of human ETEC strains to adhere to human proximal small intestinal mucosa. ETEC strain B7A (O148:H28) was selected for study because it belongs to an epidemiologically important serotype and does not produce a known CFA, and yet it is known to be pathogenic and cause diarrheal disease in human volunteers. Results of an human enterocyte adhesion assay indicated that some bacteria in cultures of B7A produced adhesive factors. To select for such bacteria, cultured human duodenal mucosal biopsy samples were infected with B7A for up to 12 h, after which time a large percentage of the mucosal surface became colonized by bacteria. A new fimbrial structure morphologically distinct from CFA/I, CFA/II, and E8775 fimbriae and consisting of curly fibrils (approximately 3 nm in diameter) was readily identified when bacteria were subcultured from the mucosa and examined by electron microscopy. Identical fimbriae were produced by ETEC strain 1782-77 of the same serotype. Identification of these fimbriae only on bacteria subcultured from human intestinal mucosa strongly suggests that they promote mucosal adhesion of ETEC serotype O148:H28 and thus represent a potentially new human ETEC CFA. PMID- 2878889 TI - Ethnic composition, age and sex, together with location and standard of housing as determinants of HLTV-I infection in an urban Trinidadian community. AB - The presence of antibody to human T-cell leukaemia virus (HLTV-I) has been assessed in 2,143 men and women who represent 83% of all adults aged 35 to 69 years resident in a defined urban community in Trinidad. Individuals of African descent had a higher sero-positivity rate (7.0%) than those originating from India (1.4%), Europe (0%) or of mixed descent (2.7%). Women were infected more frequently than men, and the prevalence of infection increased with age in both sexes. Sero-positivity rates were significantly increased in adults who lived in housing of poor quality (p less than 0.001) or close to water courses (p less than 0.025). These data and others raise the possibility that one route of HLTV-I transmission may be via insect vectors under particular domestic circumstances. PMID- 2878890 TI - Antibodies to HTLV-I in Nigerian blood-donors, their relatives and patients with leukaemias, lymphomas and other diseases. AB - Antibodies to HTLV-I have been detected in sera from 15 (2.0%) of 736 adult blood donors in Nigeria, in 4 (20.0%) of 20 patients with chronic lymphatic leukaemia, 3 (10.0%) of 30 with non-Hodgkin's lymphoma, one of 12 with Burkitt's lymphoma and one of 7 with acute lymphoblastic leukaemia. The frequency of positivity was higher (3.6%) in the blood-donors from the guinea and wooded savanna of northern Nigeria than in those from the rain-forest and mangrove swamps of southern Nigeria (1.8% in Lagos and 0.7% in Calabar). Two of the 3 seropositive patients with lymphoma had clinical presentation and courses similar to those of Japanese and Caribbean patients with adult T-cell leukaemia/lymphoma. PMID- 2878891 TI - Experimental inoculation of monkeys with autologous lymphoid cell lines immortalized by and producing human T-cell leukemia virus type-I. AB - Cynomolgus monkeys and squirrel monkeys were inoculated with autologous lymphoid cell lines immortalized by and producing human T-cell leukemia virus type-I (HTLV I) in order to serve as an animal model of adult T-cell leukemia (ATL). The autologous cell lines were established from peripheral blood mononuclear cells (PBMC) from each monkey by co-cultivation with lethally irradiated MT-2 cells producing HTLV-I. All of these cell lines, which had monkey karyotypes, grew continuously without addition of interleukin-2 (IL-2) and expressed virus specific proteins of HTLV-I and IL-2 receptor. After inoculation with the autologous cell lines, specific antibodies against HTLV-I proteins could be detected in their plasma, and transformed HTLV-I-infected cells could be recovered from their peripheral blood for at least 6 months. However, no signs of ATL have been observed to data, i.e. 2 years after inoculation. PMID- 2878892 TI - Analysis of the inhibition of tumour metastasis by sulphated polysaccharides. AB - Lung metastases resulting from the intravenous (i.v.) injection of cells from the rat mammary adenocarcinoma 13762 MAT were significantly reduced by a variety of sulphated polysaccharides, the most effective being heparin, fucoidan and Carrageenan lambda. Although all the inhibitory polysaccharides were anticoagulants, it is unlikely that anticoagulation is the total explanation of their antimetastatic effect because: (i) heparin preparations from 2 different suppliers, although exhibiting comparable anticoagulant activities, differed 10 fold in their antimetastatic capability; (ii) certain sulphated polysaccharides consistently gave a 30% difference in the number of metastatic lesions, yet exhibited identical anticoagulant activity; and (iii) the entrapment of 13762 MAT cells in the lung was not impaired by heparin or fucoidan. It was more probable that the sulphated polysaccharides were interfering with the passaging of tumour cells across the capillary wall as heparin significantly inhibited metastasis when injected up to 3 hr after lodgement, and heparin and fucoidan caused a gradual loss of tumour cells from the lung which only became apparent greater than 1 hr following cell lodgement. The data did not eliminate the possibility that tumour cell adhesion to the endothelium occurred via sulphated polysaccharide recognition. A negative correlation existed between the sulphated polysaccharides that bound to the surface of the tumour cells and those that inhibited metastasis. PMID- 2878893 TI - The handwriting test as an aid to neuroleptic dosage. PMID- 2878894 TI - A biopsychosocial model of premenstrual syndrome. AB - The authors describe the application of a biopsychosocial model to premenstrual syndrome. In this model one assumes that premenstrual syndrome is the result of an interaction between biologic, psychologic, and social factors. A six-point approach to the evaluation of women with multiple premenstrual symptoms is also presented. Finally, the benefits of this model for the clinician and investigator are reviewed. PMID- 2878895 TI - Further data on the usefulness of combined high-dose estrogen and human menopausal gonadotropins for cervical factor. AB - We report here our series of seven patients treated for cervical infertility with combined high-dose conjugated estrogen and human menopausal gonadotropins. Nine of 11 treatment cycles (81.8%) were ovulatory, and 57.1% of treated patients conceived (three single pregnancies and one set of quadruplets). Criteria for selection of patients for this combined therapy are established. PMID- 2878896 TI - The possible role of Trichomonas vaginalis as a "vector" for the spread of other pathogens. PMID- 2878897 TI - The combined use of human menopausal gonadotropin and Parlodel (bromocriptine) for in vitro fertilization. AB - A successful pregnancy resulting from in vitro fertilization and embryo transfer in which bromocriptine was utilized for ovulation induction is reported. Suppression of transient hyperprolactinemia during induction of ovulation is suggested. PMID- 2878898 TI - Antifertility effects of a potent LH-RH antagonist in male and female rats. AB - The antifertility effects of the antagonistic analogue N-Ac-D-p-Cl-Phe1,2,D Trp3,D-Arg6,D-Ala10-LH-RH (ORG 30276) were investigated in male and female rats. Male rats were treated with ORG 30276 at doses of 10 micrograms/kg, 100 micrograms/kg, or 1000 micrograms/kg per day for 60 days. The control rats were injected with the vehicle only. The treatment with the highest dose of the antagonist caused a significant decrease in the weights of the anterior pituitaries, testes, seminal vesicles, and ventral prostates and reduced serum and pituitary LH levels. The intermediate dose of the antagonist affected only seminal vesicle weights. The histology of the testes from the rats treated with the highest dose showed that the spermatogenesis was markedly depressed and did not advance beyond the stage of spermatocyte I; the interstitium showed cells of fibroblastic appearance. Twenty days after stopping treatment with the highest dose of the analogue there was a marked recovery of the weight of the testes, seminal vesicles, and ventral prostates. However, the animals were still infertile when caged with female rats. Sixty days after treatment the animals had recovered testicular function and fertility. The offspring were normal, with no evidence of genetic abnormalities. Female rats were injected with ORG 30276 at doses of 10 micrograms/kg, 100 micrograms/kg, or 1000 micrograms/kg per day for 14 days. The treatment with ORG 30276 did not modify body weights, but anterior pituitary and uterine weights were significantly decreased in the group of rats treated with the highest dose of the antagonist. Ovarian weights were decreased significantly in all the three groups treated with ORG 30276.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878899 TI - Inhibitory properties of several synthetic compounds towards human and goat acrosin, and trypsin. AB - Various synthetic inhibitors were tested for their inhibitory effects on highly purified human and goat acrosin. Bovine pancreatic trypsin was included for comparison. The molar concentrations causing 50% inhibition of the enzymes show that several guanidino compounds were highly active. The most active compound, ethyl-p-(6-guanidinohexanoyloxy) benzoate methane sulfonate (EGBM) produced 50% inhibition of human acrosin, goat acrosin, and trypsin at 5.0 X 10(-7), 8.4 X 10( 7), and 6.5 X 10(-7) M concentrations, respectively. Ethyl-p-guanidinobenzoate had an eightfold higher inhibitory power towards trypsin than to human sperm acrosin. Results on the Ki determinations showed that EGBM possessed the highest antiacrosin and antitrypsin properties, indicating that the compound has very good potential as an antifertility agent. PMID- 2878900 TI - Frequency and size of atherosclerotic plaques in vasectomized diabetic monkeys. AB - Male rhesus monkeys were used to elucidate the combined effect of vasectomy and diabetes on frequency and size of atherosclerotic plaques. Four groups were made: in two, bilateral vasectomy was performed, and the other two were subjected to sham vasectomy. Half of the vasectomized and sham-vasectomized monkeys were made diabetic by intravenous injection of alloxan. The animals were observed for a period of one year. Clinical examination revealed bilateral cataract in 40% of the diabetic animals. Marked hyperglycemia along with significant increase of serum triglycerides and free fatty acids was noted in diabetic monkeys. Vasectomy per se did not alter serum lipid levels and overall atherosclerotic plaque score in nondiabetic monkeys. However, the combination of vasectomy with diabetic state led to significant increase of overall atherosclerotic plaque score in coronary and renal arteries. PMID- 2878901 TI - Modulatory effect of prostaglandin E2 on the immune response in mice, with special reference to anti-sperm immunity. AB - The intraperitoneal administration of prostaglandin E2 (PgE2) considerably delayed the rejection of allogeneic skin grafts, both in the primary (first set) and secondary (second set) reaction, and inhibited the production of plaque forming cells after antigenic stimulation with sheep red blood cells. In addition, the treatment of mice with PgE2 during their immunization with allogeneic epididymal spermatozoa resulted in a markedly slower rejection of the following skin grafts from the donor's strain in comparison with the animals injected with spermatozoa only. Evidence was also found concerning the immunosuppressive effect of PgE2 on the humoral immune response against sperm antigens. The possible immunoregulatory role of PgE2 in the natural immune tolerance to sperm antigens is discussed. PMID- 2878902 TI - The effect of anti-inflammatory and rheumatoid disease modifying drugs on prolonged immune and non-immune inflammation in the six-day air pouch of rats. AB - The six-day air pouch model of synovitis in rats was used to study the effects of non-steroidal and anti-rheumatic drugs on cell accumulation and exudate formation. Inflammation was induced in the six-day air pouch either with the non immune irritant carrageenan or the immune irritant Bordetella pertussis. Indomethacin reduced cell accumulation and exudate formation in both models. In contrast levamisole and D-penicillamine were unable to reduce either parameter, D penicillamine actually producing at certain times a pro-inflammatory effect. The steroid dexamethasone caused the total inhibition of inflammatory exudate formation and cell accumulation. The six-day air pouch of rats may therefore be useful for the detection of agents which inhibit chronic inflammation. PMID- 2878903 TI - Neuroendocrine control of secretion in pancreatic and parotid gland acini and the role of Na+,K+-ATPase activity. AB - The results of our investigations into the localization of Na+,K+-pump activity in pancreatic and parotid acinar cells and the effects of hormones and neurotransmitters on pump turnover can be integrated with data on other aspects of stimulus-response coupling to construct models of the neurohumoral control of protein, fluid, and electrolyte secretion (Fig. 23). In both tissues, Ca2+ and cyclic AMP serve as intracellular messengers. In pancreatic acinar cells, the Ca2+-dependent pathway activated by the occupation of CCK or cholinergic receptors provides the primary stimulus for digestive enzyme secretion. Cyclic AMP plays a comparatively minor role; VIP and secretin are much less effective stimulators of protein secretion. Conversely, cyclic AMP levels in parotid acinar cells, which are modulated primarily through occupation of beta-adrenergic receptors, are a major determinant of enzyme secretion. Activation of the Ca2+ dependent pathway by cholinergic or alpha-adrenergic agonists or substance P is less important. The presence of dual control processes in each gland suggests that the observed differences in effectiveness of cyclic AMP- versus Ca2+ dependent secretagogues may reflect not different mechanisms, but rather a shift in the relative emphasis placed on each pathway. This emphasis could conceivably result from subtle variations in the interaction between cellular protein kinases and phosphatases and their phosphoprotein substrates. Electrolyte secretion, on the other hand, appears to involve both discrete and common entities. In pancreatic acinar cells from rodent species, cholinergic or CCK receptor occupancy elicits a Ca2+-dependent increase in the open-state probability of nonselective cation channels in the basolateral plasma membrane. The resultant influx of Na+ and efflux of K+ is most probably the factor which activates Na+, K+-pumps. Based on electron probe studies of the effects of cholinergic agonists on acinar cell Na+ and K+ contents discussed earlier, a transient reduction in the intracellular K+/Na+ ratio of up to 4-fold may occur. A shift of this magnitude in the cytoplasmic microenvironment of the Na+, K+-pump clearly would have a stimulatory influence (see discussion by Jorgensen, 1980). In addition, Ca2+ itself may have direct effects on Na+,K+-pump activity. Calcium at levels much above 1 microM progressively inhibits Na+,K+-ATPase activity (Tobin et al., 1973; Yingst and Polasek, 1985). In unstimulated guinea pig pancreatic acinar cells, Ca2+i measured by quin-2 fluorescence was 161 +/- 13 nM (Hootman et al., 1985a) which increased to a maximal concentration of 803 +/- 122 nM following CCh stimulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2878904 TI - The circumventricular organs of the mammalian brain with special reference to monoaminergic innervation. PMID- 2878905 TI - [Antirheumatic drug-induced damage of the gastroduodenal mucosa: approach to prevention]. PMID- 2878906 TI - [Neurogenic mechanisms of skin circulation]. PMID- 2878907 TI - [Pathogen-host relations in sexually transmitted diseases]. AB - The host-parasite relationship between the major causative agents of sexually transmitted diseases, e.g. Neisseria gonorrhoeae, Treponema pallidum and Trichomonas vaginalis, and their target cells in the urogenital tract can generally be studied in suitable cell and organ cultures. Experience with N. gonorrhoeae predominantly gained from fallopian-tube organ cultures shows that there are several prerequisites for adherence as the first step of pathogenesis. They range from the type of bacterial pili to the type of epithelial cell. Later the function of these cells is damaged by subcellular toxins of a lipopolysaccharide nature. The cocci are phagocytosed, which eventually leads to definite (ultra-) structural alterations. These processes are not only described in detail but also compared with those found with other bacterial species and target cells. Possible predisposing factors in the host are also taken into account. Finally the need for investigating the effect of antibiotics on the host parasite relationship is stressed. PMID- 2878908 TI - Histamine in endocrine cells in the stomach. A survey of several species using a panel of histamine antibodies. AB - Antibodies to histamine were used to examine the localization of the amine in cells of the stomach and upper small intestine of a great variety of species, including cartilaginous and bony fish, amphibia, reptiles (lizard), birds (chicken) and a large number of mammals. In all species gastric histamine was localized in endocrine cells (invariably found in the epithelium) and mast cells (usually with an extra-epithelial localization). The endocrine cells were identified as such by immunostaining with antibodies to chromogranin A and the mast cells were identified by toluidine blue staining. Histamine-immunoreactive endocrine cells were found almost exclusively in the acid-producing part of the stomach; only rarely were such cells observed in the pyloric gland area. They were fairly numerous in the gastric mucosa of the two subclasses of fish as well as in the amphibia and reptile species studied. Here, the majority of the histamine-immunoreactive endocrine cells seemed to have contact with the gastric lumen (open type cells) and were located in the surface epithelium (certain fish only) or together with mucous neck cells at the bottom of the pits. In the chicken, histamine-immunoreactive endocrine cells were numerous and located peripherally in the deep compound glands. They were without contact with the lumen (closed type) and had long basal extensions ("paracrine" appearance), running close to the base of the oxyntic-peptic cells. In mammals, the number of histamine-immunoreactive endocrine cells in the stomach varied greatly. They were particularly numerous in the rat and notably few in the dog, monkey and man. In all mammals, the histamine-immunoreactive endocrine cells were of the closed type and located basally in the oxyntic glands. They often had a "paracrine" appearance with long basal processes. Histamine-storing mast cells, finally, were few in both subclasses of fish as well as in the amphibian species and in the lizard. They were fairly numerous in chicken proventriculus (beneath the surface epithelium), few in the oxyntic mucosa of mouse, rat and hamster, moderate in number in hedgehog, guinea-pig, rabbit, pig and monkey, and numerous in cat, dog and man.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2878909 TI - Morphological changes of sensory CGRP-immunoreactive and sympathetic nerves in peripheral tissues following chronic denervation. AB - The morphological relationship between sensory and sympathetic nerves was studied in tissues of the eye and the oral cavity following chronic sympathetic or sensory denervation. Immunoreactivities for calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH) were used as indexes to assess the changes of the two nerve populations after denervation. Following surgical sympathectomy, a marked increase of CGRP-containing fibres was seen in all tissues studied, while TH-imunoreactive fibres were totally depleated. Conversely, after capsaicin treatment, an increase of TH-immunoreactive nerves was found in the same tissues, concomitant with a sharp decrease of CGRP-immunoreactive nerves. These changes were particularly evident in iridial stroma and around blood vessels in all tissue, where sensory and sympathetic nerves have a closely overlapping distribution pattern. The altered proportion of sensory peptide- and catecholamine-containing nerves following sympathetic and sensory denervation suggest that there is a reciprocal trophic influence between the two nerve subsets, possibly with the intervention of neurotrophic substances such as nerve growth factor. These results indicate a close interaction between sensory peptidergic and sympathetic nervous systems in peripheral organs. PMID- 2878910 TI - Isolation and allelic polymorphism of cDNA clones and genomic clones of HLA-DP heavy and light chains. AB - From a human cDNA library constructed from consanguineous HLA-homozygous cell line AKIBA (HLA-A24, Bw52, DR2, Dw12, Cp63 Cp63: a new DP type), cDNA clones encoding the heavy and light chains of an HLA-DP Cp63 alloantigen were isolated and analyzed by restriction enzyme mapping and nucleotide sequence determination. Allelic comparisons of DP alpha and DP beta cDNA sequences showed that the amino acid sequence of the DP alpha chain was less polymorphic than that of the DP beta chain. In the DP beta chain, the polymorphic region was restricted to the beta 1 domain. We also isolated and characterized 15 genomic phage clones spanning a 74 kilobase (kb) pair of the DP region which were found to contain one DP alpha gene, one DP-like alpha gene, one DP beta gene, and one DP-like beta gene. Genomic blot analyses with different HLA-DP type cell lines using DP alpha cDNA as a probe revealed EcoRI fragment length polymorphism around the DP alpha gene. PMID- 2878911 TI - A rheumatology practice in a community-based medical school. PMID- 2878912 TI - Management of accessory nerve injury. PMID- 2878913 TI - In pursuit of professional freedom 2. PMID- 2878915 TI - Muscle biopsy in the evaluation of pyrexia of unknown origin (PUO). PMID- 2878914 TI - 'Unstable angina'. Aetiologic and therapeutic implications. PMID- 2878916 TI - Periarteritis nodosa with mononeuritis multiplex. PMID- 2878917 TI - Immunoelectron microscopic analysis of elongation of type 1 fimbriae in Escherichia coli. AB - Using 10- and 20-nm-diameter gold particles conjugated to an antifimbrial monoclonal antibody, we analyzed the location of assembly of newly formed subunits on growing type 1 fimbriae of Escherichia coli. Fimbriae were removed from an E. coli K-12-derived strain, CSH50, by blending. Blended cells were allowed to regenerate their fimbriae in growth medium for approximately 25 min, after which they were labeled with a 20-nm-gold-monoclonal antibody probe. Continued outgrowth of these labeled fimbriae was allowed for additional time intervals, after which they were labeled with a 10-nm-gold-monoclonal antibody probe. The resulting fimbriae, double labeled with 10- and 20-nm-diameter gold particles, were examined in an electron microscope. The pattern of labeling on individual fimbrial organelles indicated morphologically that newly synthesized subunits are added to a growing organelle at its base. PMID- 2878918 TI - Changes in amino acid and nucleotide pools of Rhodospirillum rubrum during switch off of nitrogenase activity initiated by NH4+ or darkness. AB - Amino acid and nucleotide pools were measured in nitrogenase-containing Rhodospirillum rubrum cultures during NH4+- or dark-induced inactivation (switch off) of the Fe protein. A big increase in the glutamine pool size preceded NH4+ switch-off of nitrogenase activity, but the glutamine pool remained unchanged during dark switch-off. Furthermore, methionine sulfoximine had no effect on the rate of dark switch-off, suggesting that glutamine plays no role in this process. In the absence of NH4+ azaserine, an inhibitor of glutamate synthate, raised glutamine pool levels sufficiently to initiate switch-off in vivo. While added NH4+ substantially increased the size of the nucleotide pools in N-limited cells, the kinetics of nucleotide synthesis were all similar and followed (rather than preceded) Fe protein inactivation. Darkness had little effect on nucleotide pool sizes. Glutamate pool sizes were also found to be important in NH4+ switch-off because of the role of this molecule as a glutamine precursor. Much of the diversity reported in the observations on NH4+ switch-off appears to be due to variations in glutamate pool sizes prior to the NH4+ shock. The nitrogen nutritional background is an important factor in determining whether darkness initiates nitrogenase switch-off; however, no link has yet been established between this and NH4+ (glutamine) switch-off. PMID- 2878919 TI - Morphogenetic expression of Bacteroides nodosus fimbriae in Pseudomonas aeruginosa. AB - Type 4 fimbriae are found in a range of pathogenic bacteria, including Bacteroides nodosus, Moraxella bovis, Neisseria gonorrhoeae, and Pseudomonas aeruginosa. The structural subunits of these fimbriae all contain a highly conserved hydrophobic amino-terminal sequence preceding a variable hydrophilic carboxy-terminal region. We show here that recombinant P. aeruginosa cells containing the B. nodosus fimbrial subunit gene under the control of a strong promoter (pL, from bacteriophage lambda) produced large amounts of fimbriae that were structurally and antigenically indistinguishable from those produced by B. nodosus. This was demonstrated by fimbrial isolation and purification, electrophoretic and Western transfer analyses, and immunogold labeling and electron microscopy. These results suggest that type 4 fimbriated bacteria use a common mechanism for fimbrial assembly and that the structural subunits are interchangeable, thereby providing a basis for the development of multivalent vaccines. PMID- 2878920 TI - Characterization of the surface protein layers of the mosquito-pathogenic strains of Bacillus sphaericus. AB - The protein surface layers on the cell walls of mosquito-pathogenic and nonpathogenic Bacillus sphaericus strains were studied by structural, biochemical, and serological methods. The surface structure of two representative insect-pathogenic strains had the form of a delicate linear array with a repeat interval of 5 nm. This was distinctly different from the tetragonal array of the P-1 strain in spacing and arrangement. The surface layers were composed of acidic glycoproteins with molecular weights ranging from approximately 133,000 to 155,000. Peptide mapping and serological analysis of the surface proteins revealed eight distinct groups among the pathogens. These groups were very similar to the groupings determined by flagellar-antigen serotyping and bacteriophage typing. PMID- 2878921 TI - Genes encoding the beta and epsilon subunits of the proton-translocating ATPase from Anabaena sp. strain PCC 7120. AB - The genes encoding the beta (atpB) and epsilon (atpE) subunits of the ATPase from the cyanobacterium Anabaena sp. strain PCC 7120 were cloned, and their sequences were determined. atpB and atpE are each single-copy genes in the Anabaena genome. The two genes are separated by a 96-base-pair intergenic spacer and transcribed as a single mRNA of 2.3 kilobases that initiates approximately 200 base pairs upstream of the atpB coding region. The predicted translation product of atpB has 81 and 68% amino acid identity with the corresponding proteins from spinach chloroplasts and Escherichia coli, respectively. The atpE gene product is less conserved, with 41 and 33% amino acid identity with the corresponding proteins from spinach chloroplasts and E. coli, respectively. The organization of the Anabaena atpB and atpE genes relative to adjacent genes differs from that of both E. coli and chloroplasts. PMID- 2878922 TI - Electrophoretic behavior of the H+-ATPase proteolipid from bovine heart mitochondria. AB - The proteolipid subunit of H+-ATPase was labeled by [14C]N,N' dicyclohexylcarbodiimide in bovine heart mitochondria. The radioactive labeling was followed using various systems of sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). When using discontinuous SDS-PAGE (Laemmli, U.K., 1970, Nature (London) 227, 680-685) a monomeric (Mr 7600 +/- 1500) and a dimeric form (Mr 17,800 +/- 1200) of the proteolipid were detected, while only the monomeric form was found on urea (8 M) containing gels (SDS-PAGE according to Laemmli; or Swank, R. T., and Munkers, K. D., 1971, Anal. Biochem. 39, 462-477). When using SDS-PAGE with Na-Pi buffer (Weber, K., and Osborn, M., 1969, J. Biol. Chem. 244, 4406-4442), only a dimeric form of the proteolipid (Mr 15,000 +/- 1000) was detected. Experimental data indicate that the different patterns of proteolipid separation are related to the presence of the two distinct proteolipid conformations in the SDS solution. PMID- 2878923 TI - The interaction of phosphorylated oligosaccharides and lysosomal enzymes with bovine liver cation-dependent mannose 6-phosphate receptor. AB - We have analyzed the interaction of phosphorylated oligosaccharides and lysosomal enzymes with immobilized bovine liver cation-dependent mannose-6-P receptor. Oligosaccharides with phosphomonoesters were the only species that interacted with the receptor, and molecules with two phosphomonoesters showed the best binding. Lysosomal enzymes with several oligosaccharides containing only one phosphomonoester had a higher affinity for the receptor than did the isolated oligosaccharides, indicating the possible importance of multivalent interactions between weakly binding ligands and the receptor. The binding of a mixture of phosphorylated lysosomal enzymes to the cation-dependent Man-6-P receptor was markedly influenced by pH. At pH 6.3, almost all of the lysosomal enzymes bound to the receptor; whereas at pH 7.0-7.5, approximately one-third of the material passed through the column, one-third interacted weakly, and one-third bound tightly. The distribution of individual lysosomal enzyme activities was similar to that of the total material. The species of phosphorylated oligosaccharides present on the lysosomal enzymes which interacted poorly with the receptor were similar to those found on the tightly bound material and included species of oligosaccharides with two phosphomonoester groups. Isolated oligosaccharides of this type bound to the receptor over the entire pH range tested. These findings indicate that at neutral pH the phosphorylated oligosaccharides on some lysosomal enzyme molecules are oriented in a manner which makes them inaccessible to the binding site of the cation-dependent Man-6-P receptor. Since the same enzymes bind to the cation-independent Man-6-P receptor at neutral pH, at least a portion of the phosphomannosyl residues must be exposed. We conclude that small variations in the pH of the Golgi compartment where lysosomal enzymes bind to the receptors could potentially modulate the extent of binding to the two receptors. PMID- 2878924 TI - Glutamine synthetase isozymes in elasmobranch brain and liver tissues. AB - Glutamine synthetase is present as isozymic forms in the elasmobranchs Squalus acanthias (dogfish shark) and Dasyatis sabina (stingray). Subcellular fractionation of elasmobranch brain and liver tissue shows the enzyme to be predominantly cytosolic in the former tissue and mitochondrial in the latter. For the cytosolic brain enzyme, the subunit Mr equals 42,000 in the stingray and 45,000 in the shark, as determined by sodium dodecyl sulfate-gel electrophoresis/Western blotting. The subunit Mr = 45,000 and 47,000, respectively, for stingray and dogfish mitochondrial liver enzymes. Translation of total brain RNA from both species gives immunoprecipitable nascent peptides of the same size as their respective mature enzymes. However, in liver tissue, translation of glutamine synthetase mRNA yields peptides of higher Mr than that of the mature enzymes. In dogfish liver, Mr = 50,000 for the translation product and, in stingray liver, Mr = 48,000. This suggests that the translocation of the enzyme into liver mitochondria may be via a signal or leader sequence mechanism. The larger liver isozyme of elasmobranch glutamine synthetase is found in kidney where it is also known to be mitochondrial. The smaller cytosolic isozyme occurs in retina, heart, gill, and rectal gland tissue as well as in brain. PMID- 2878925 TI - A single mutation confers vanadate resistance to the plasma membrane H+-ATPase from the yeast Schizosaccharomyces pombe. AB - A single-gene nuclear mutant has been selected from the yeast Schizosaccharomyces pombe for growth resistance to Dio-9, a plasma membrane H+-ATPase inhibitor. From this mutant, called pma1, an ATPase activity has been purified. It contains a Mr = 100,000 major polypeptide which is phosphorylated by [gamma-32P] ATP. Proton pumping is not impaired since the isolated mutant ATPase is able, in reconstituted proteoliposomes, to quench the fluorescence of the delta pH probe 9 amino-6-chloro-2-methoxy acridine. The isolated mutant ATPase is sensitive to Dio 9 as well as to seven other plasma membrane H+-ATPase inhibitors. The mutant H+ ATPase activity tested in vitro is, however, insensitive to vanadate. Its Km for MgATP is modified and its ATPase specific activity is decreased. The pma1 mutation decreases the rate of extracellular acidification induced by glucose when cells are incubated at pH 4.5 under nongrowing conditions. During growth, the intracellular mutant pH is more acid than the wild type one. The derepression by ammonia starvation of methionine transport is decreased in the mutant. The growth rate of pma1 mutants is reduced in minimal medium compared to rich medium, especially when combined to an auxotrophic mutation. It is concluded that the H+ ATPase activity from yeast plasma membranes controls the intracellular pH as well as the derepression of amino acid, purine, and pyrimidine uptakes. The pma1 mutation modifies several transport properties of the cells including those responsible for the uptake of Dio-9 and other inhibitors (Ulaszewski, S., Coddington, A., and Goffeau, A. (1986) Curr. Genet. 10, 359-364). PMID- 2878926 TI - Sequences distal to the mitochondrial targeting sequences are necessary for the maturation of the F1-ATPase beta-subunit precursor in mitochondria. AB - The beta-subunit of the mitochondrial F1-ATPase is synthesized as a precursor in the cytoplasm which is delivered through two bilayers bounding the mitochondria prior to its assembly with other proteins into a functional complex. In order to determine the role of the amino-terminal 50 residues of the precursor on its localization, maturation, and assembly, a set of deletions within this region of the ATP2 gene encoding the beta-subunit has been analyzed. These studies reveal that deletions between residue 10 of the F1 beta-presequence and residue 36 can still direct in vivo mitochondrial import and assembly of the mutant subunit into a functional complex. Deletions within ATP2 which contain less than the first 10 residues of the precursor are not imported. Thus, the extreme amino terminus (about half of the transient presequence) of the F1 beta-subunit can direct its mitochondrial import. The wild-type F1 beta-subunit precursor is matured by the matrix-located metalloprotease at Lys19-Gln20; however, small in-frame deletions up to 17 residues distal to this site fail to be matured either in vitro or in vivo. This nonmatured F1 beta-subunit is also assembled into a functional enzyme and supports growth of its host on a nonfermentable carbon source. These data indicate that maturation of the F1 beta-subunit precursor is dependent on a protein sequence located distal to the proteolytic maturation site which is distinct from the mitochondrial targeting sequence. PMID- 2878927 TI - Biosynthetic thiolase from zoogloea ramigera. I. Preliminary characterization and analysis of proton transfer reaction. AB - The biosynthetic thiolase, from Zoogloea ramigera, involved in generation of acetoacetyl-CoA for poly-beta-hydroxybutyrate synthesis, has been prepared pure in quantity for initial structural characterization of this homotetrameric enzyme. Edman degradation provided the sequence of the NH2 terminal 25 residues and an active site cysteine-containing nonapeptide labeled on stoichiometric inactivation by iodoacetamide. Both sequences were used to align the encoding DNA sequence of the cloned gene as described in an accompanying paper. Synthetic analogs of acetoacetyl-S-CoA, modified in the CoA moiety, were prepared and tested, and acetoacetyl-S-pantetheine 11-pivalate 1 was shown to have a kcat/Km of 6.4 X 10(6) M-1 s-1, comparable to the kcat/Km of 2 X 10(7) M-1 s-1 for acetoacetyl-S-CoA. The pantetheine pivalate group facilitates nonaqueous synthetic manipulations and may be generally useful as a CoA replacement. We have also prepared the carba analog of 1, with CH2 replacing S, to yield a beta diketone analog 10 of acetoacetyl-S-CoA and the corresponding methyl ketone analog 9 of acetyl-S-CoA. These analogs have been used to prove the ability of Z. ramigera thiolase to catalyze proton abstraction from the C-2 methyl group of the acetyl portion of substrate in a transition state separate from C-C bond formation. NMR studies in D2O show exchange only when condensation is possible. Further studies with [2-3H]acetyl-CoA show there is neither pre-equilibrium washout nor detectable kH/kT expressed in turnover and provide no evidence for a discrete acetyl-CoA C-2 carbanion or a nonconcerted reaction. PMID- 2878928 TI - Biosynthetic thiolase from Zoogloea ramigera. II. Inactivation with haloacetyl CoA analogs. AB - The thiolase involved in biosynthesis of poly-beta-hydroxybutyrate in Zoogloea ramigera generates an acetyl-enzyme species during catalysis. Up to 0.86 [14C] acetyl eq/subunit of this homotetrameric enzyme is accumulated by acid precipitation in the presence of [14C]acetyl-CoA. Gel filtration of the same solutions produced only 7% acetyl-enzyme suggesting hydrolytic lability of the acetyl-enzyme during the 10-min isolation at 4 degrees C. In an effort to identify active site residues which may function as basic groups to deprotonate at C-2 of acetyl-CoA to generate the required nucleophilic equivalent in carbon carbon bond formation, we have prepared and tested haloacetyl-thioesters, oxoesters, and amides in the panthetheine pivalate series (Davis, J. T., Moore, R. N., Imperiali, B., Pratt, A. J., Kobayashi, K., Masamune, S., Sinskey, A. J., and Walsh, C. T. (1987) J. Biol. Chem. 262, 82-89). The [14C]bromoacetyl-oxoester alkylatively inactivates thiolase irreversibly with stoichiometric incorporation of four labels/tetramer. Determination of amino acid composition of the radiolabeled tryptic peptide indicated trapping of Cys-89 (Peoples, O. P., Masamune, S., Walsh, C. T., and Sinskey, A. J. (1987) J. Biol. Chem. 262, 97 102), the same residue modified by iodoacetamide. When the bromoacetyl-thioester was used, inactivation was pH-dependent. The data are consistent with the competition of two processes, acylation, and alkylation. Direct (rather than secondary) alkylation of thiolase by the inactivator accounts for the significant 14C incorporation into thiolase with the thioester labeled with [14C] in the pantetheine pivalate moiety. It appears likely that the haloacetyl analogs described herein should be generally useful for affinity labeling other enzymes using acetyl-CoA as a substrate. PMID- 2878929 TI - Biosynthetic thiolase from Zoogloea ramigera. III. Isolation and characterization of the structural gene. AB - The gene coding for the biosynthetic thiolase from Zoogloea ramigera has been isolated by using antibody screening methods to detect its expression in Escherichia coli under the transcriptional control of the lac promoter. We have located and determined the nucleotide sequence of the gene. The structural gene is 1173 nucleotides long and codes for a polypeptide of 391 amino acids; 282 nucleotides 5' and 58 nucleotides 3' to the coding sequence are also reported. By comparing the amino acid sequence data predicted from the gene with data determined experimentally, we have derived the complete primary structure of thiolase. A catalytically essential cysteine is located at residue 89. The DNA sequence presented has a very high G/C content, 66.2%, typical of the Z. ramigera genome. In the coding region, this increases to 68.2% and is strongly reflected in the codon usage which demonstrates a strong preference for G or C in the third position. Examination of the 5'-flanking sequence establishes that the NH2 terminal methionine is specified by an ATG codon, 7 nucleotides downstream from a Shine-Dalgarno sequence. PMID- 2878930 TI - Potassium-dependent assembly of coated pits: new coated pits form as planar clathrin lattices. AB - Previous studies have shown that when human fibroblasts are depleted of intracellular K+, coated pits disappear from the cell surface and the receptor mediated endocytosis of low density lipoprotein (LDL) is inhibited. We have now used the K+ depletion protocol to study several aspects of coated pit function. First, since coated pits rapidly form when K+-depleted fibroblasts are incubated in the presence of 10 mM KCl, we studied the sequence of assembly of coated pits as visualized in carbon-platinum replicas of inner membrane surfaces from cells that had been incubated in the presence of K+ for various times. New coated pits initially appeared as planar clathrin lattices that increased in size by the formation of polygons at the margin of the lattice. Once the lattice reached a critical size it invaginated to form coated vesicles. Second, we determined that LDL-ferritin can induce clustering of LDL receptors over noncoated membrane on the surface of K+-depleted fibroblasts; however, when these cells are subsequently incubated in the presence of K+, these clusters become associated with newly formed coated pits and are internalized. Finally, we determined that K+ depletion inhibits the assembly of coated pits, but that existing coated pits in K+-depleted cells are able to internalize LDL. These results suggest that the clathrin lattice of coated pits is actively involved in membrane shape change during endocytosis and that the structural proteins of the lattice are cyclically assembled and disassembled in the process. PMID- 2878932 TI - Hypothalamic releasing hormones: clinical possibilities. PMID- 2878931 TI - Characterization of endocytic compartments using the horseradish peroxidase diaminobenzidine density shift technique. AB - We have employed a modification of the horseradish peroxidase (HRP) diaminobenzidine density shift technique of Courtoy et al. (J. Cell Biol., 1984, 98:870-876) to examine the biochemical properties of the endosome. This organelle is involved in receptor recycling and the sorting of internalized receptor ligand complexes. Transferrin covalently bound to HRP was used to place peroxidase activity specifically within the endosome. The peroxidase-catalyzed polymerization of diaminobenzidine within these vesicles causes an increase in buoyant density, thus allowing them to be separated from other membranes. Using this technique we demonstrate that 125I-low density lipoprotein, 131I-epidermal growth factor, and Tf-HRP are internalized into the same endosome. We discovered that the diaminobenzidine reaction product "cross-links" the lumen of the vesicle, rendering vesicular components detergent insoluble. Furthermore, the reaction inactivates enzymatic activities associated with the endosome. Thus, the diaminobenzidine density shift procedure has limited usefulness in studies designed to isolate endosomal constituents. Nonetheless, we have found that the inactivation of enzymatic activities is confined to those endosomes that contain peroxidase. This selectivity allows us to define endosome-specific activities. PMID- 2878933 TI - Interleukin-2 receptors: biology and therapeutic potentials. PMID- 2878934 TI - Heterogeneity of Graves' immunoglobulin G: comparison of thyrotropin receptor antibodies in serum and in culture supernatants of lymphocytes transformed by Epstein-Barr virus infection. AB - It is well known that in patients with Graves' disease there is dissociation among values for TSH receptor antibodies such as TSH binding-inhibiting antibody (TBIAb) and thyroid-stimulating antibody (TSAb). This study was designed to compare TSH receptor antibodies in serum and in culture supernatants of lymphocytes transformed by Epstein-Barr virus (EBV) infection. TBIAb was assayed using solubilized porcine thyroid membranes and TSAb using cultured porcine thyroid cells. Transformation of peripheral lymphocytes by EBV was performed in eight untreated hyperthyroid patients with Graves' disease who had a clear dissociation between values for TBIAb and TSAb, even after multiple dilutions of serum. EBV-infected lymphocytes from a patient were distributed into the wells of 4 24-well culture plates. After the first 4-week culture, the cells in each well positive for TBIAb and/or TSAb were further distributed to 12 wells and cultured for 2 weeks. In the supernatants of 372 wells of the second culture in the 8 patients, 31 were positive for TBIAb, and 41 were positive for TSAb. Among the 76 wells positive for TSH receptor antibodies, 72 wells (94.7%) were positive in only 1 assay. These results suggest that there are two types of TSH receptor antibodies, one having a single function (TBIAb or TSAb) and the other multifunctional (both), in Graves' patients. The incidence of the single functional type is much greater than that of the multifunctional type. We conclude, therefore, that the heterogeneity of Graves' immunoglobulin G is due mainly to multiple antibodies with a single function. PMID- 2878935 TI - Evidence for thyrotropin (TSH)-blocking activity in goitrous Hashimoto's thyroiditis with assays measuring inhibition of TSH receptor binding and TSH stimulated thyroid adenosine 3',5'-monophosphate responses/cell growth by immunoglobulins. AB - There are two forms of autoimmune thyroiditis that may cause hypothyroidism: autoimmune atrophic thyroiditis (primary idiopathic hypothyroidism or primary myxedema) and autoimmune goitrous thyroiditis (Hashimoto's disease). Patients with the former have impalpable thyroid glands, and those with the latter have goiters. We studied TSH binding inhibitory immunoglobulins (TBII), TSH-stimulated cAMP response inhibitory immunoglobulins (TSII), and TSH-stimulated cell growth inhibitory immunoglobulins (TGII) in 42 patients with the former (group 1) and 115 patients with the latter (group 2). Porcine thyroid cells in primary culture and rat thyroid cells in continuous culture (FRTL-5 cells) were used to study TSII and TGII activities, respectively; TSII was expressed as percent inhibition of 0.1 mU/ml TSH-stimulated cAMP response by the patient's immunoglobulin (IgG; 1 mg/ml) during 2-h incubation, and TGII was expressed as percent inhibition of 10 mU/ml TSH-stimulated [14C]thymidine incorporation by the patient's IgG (1 mg/ml) during 24-h incubation. The new findings in this report are: some patients in both groups had TBII, TSII, and/or TGII; the frequency of the presence of TBII, TSII, and TGII in the patients with autoimmune atrophic thyroiditis was higher than that in the patients with autoimmune goitrous thyroiditis, and TSII and TGII were significantly associated with autoimmune atrophic thyroiditis; no correlation was found between goiter size and TBII, TSII, or TGII activity; and there were good correlations between TBII, TSII, and TGII activities. We also found that TSH-stimulated thymidine incorporation was through cAMP production and that the inhibitory IgGs inhibited TSH-stimulated thymidine incorporation by decreasing cAMP production in FRTL-5 cells, but not in porcine or human thyroid cells. PMID- 2878936 TI - Thyroglobulin release-stimulating activity in immunoglobulin G from patients with Graves' disease studied by human thyroid cells in vitro. AB - The ability of TSH or immunoglobulin G (G-IgG) from untreated patients with hyperthyroidism due to Graves' disease to stimulate thyroglobulin (Tg) release from human thyroid cells was studied. Thyroid tissue obtained from antithyroid drug-treated Graves' hyperthyroid patients was dispersed enzymatically and cultured in monolayers; medium was changed every 3 days. The cultured cells initially released large but declining amounts of Tg, independent of the presence of TSH (approximately 5 micrograms/dish on day 3 and approximately 1.5 micrograms/dish on day 6). After 6 days, TSH had a dose-dependent stimulatory effect on Tg release, and the peak response occurred on day 15. G-IgG-induced Tg release was found on the 12th day of culture and was maximal on day 18. Thyroid cells cultured for 12 days in the absence of TSH responded to TSH and G-IgG in a time- and dose-dependent fashion. Using 12-day cultures, Tg release-stimulating activity (Tg-RSA) was tested using 5 mg/ml (7.5 mg/dish) G-IgGs from 20 patients and 72-h incubation. The Tg-RSA of individual patients varied. However, significant correlations were found between Tg-RSA values and serum Tg concentrations or Tg-RSA and thyroid-stimulating immunoglobulin activities. No correlation was found between Tg-RSA and TSH binding inhibitor immunoglobulin activities. These results suggest that Tg-RSA can be an indicator of abnormal IgG of hyperthyroid Graves' patients. Whether the activity is identical with thyroid stimulating activity remains to be clarified. PMID- 2878938 TI - Relationship of glucagon suppression by insulin and somatostatin to the ambient glucose concentration. AB - The glucagon-suppressing activity of insulin and somatostatin were compared at high and low glucose concentrations. In normal dogs made hyperglucagonemic by phloridzin pretreatment, insulin and somatostatin suppressed glucagon at rates of 47 +/- 8 and 35 +/- 8%/h (NS), respectively, despite profound hypoglycemia. In severely hyperglycemic alloxan-diabetic dogs, insulin and somatostatin suppressed glucagon at rates of 48 +/- 13 and 54 +/- 6%/h, respectively, not different from the nondiabetic dogs. After phloridzin pretreatment to eliminate hyperglycemia in the diabetic dogs, insulin and somatostatin suppressed 51 +/- 8 and 31 +/- 10%/h (NS), respectively. Glucose infused in the phloridzin-pretreated insulin-deprived group suppressed glucagon only partially; insulin was required to reduce it further. We conclude that insulin and somatostatin suppress glucagon at similar rates irrespective of ambient glucose levels, and that diabetic hyperglucagonemia represents the summation of stimulation by insulin lack minus suppression by the associated hyperglycemia. PMID- 2878937 TI - Selective suppression of insulin-induced proliferation of cultured human hepatoma cells by somatostatin. AB - The effects of somatostatin (SRIF), insulin, and triiodothyronine (T3) on the growth of human hepatoma cells were investigated on the well-differentiated human hepatoma cell line Hep3B. Results showed that both insulin and T3 can stimulate cell growth of serum starved Hep3B cells at physiological concentrations. SRIF alone showed little growth-promoting activity. When added concurrently with insulin, however, SRIF suppressed the insulin-induced cell proliferation in a dose-dependent manner. On the other hand, SRIF had no inhibitory effect on T3 induced cell proliferation. SRIF is labile in the medium, with a half-life of about 2 h during culture incubation. SRIF did not disturb the insulin binding to its surface receptors nor inhibit the insulin-dependent receptor kinase activity of Hep3B cells in vitro. These results suggest that postreceptor regulation may be involved. The selective suppression by SRIF of insulin-induced cell growth provides an unique approach to the study of insulin actions on proliferation of human hepatoma cells. PMID- 2878939 TI - Mapping the Lowe oculocerebrorenal syndrome to Xq24-q26 by use of restriction fragment length polymorphisms. AB - A molecular linkage analysis of four large families with the Lowe oculocerebrorenal syndrome (LS) provided a subregional localization of LS to the distal long arm of the X chromosome at Xq24-q26. Probes from two loci that identify restriction fragment length polymorphisms (RFLPs) and map to Xq24-q26 showed no recombination with LS. A maximum likelihood recombination distance (theta) = 0.00 was obtained for DXS10 with the logarithm of the odds (lod) of 6.450. For DXS42, theta = 0.00 with a lod of 5.087. Assignment of the gene or genes for LS to Xq24-q26 has the potential of improving carrier detection and providing prenatal diagnosis in families at risk for the disease. PMID- 2878941 TI - Basic pharmacokinetics of bisoprolol, a new highly beta 1-selective adrenoceptor antagonist. AB - The basic pharmacokinetics of bisoprolol were investigated in three independent studies involving 23 healthy volunteers. After administering 20 mg of 14C bisoprolol orally, mean elimination half-lives of 11 hours for the unchanged drug and 12 hours for total radioactivity were observed. The enteral absorption of bisoprolol was nearly complete. Fifty percent of the dose was eliminated renally as unchanged bisoprolol and the other 50% metabolically, with subsequent renal excretion of the metabolites. Less than 2% of the dose was recovered from the feces. Intraindividual comparison of the pharmacokinetic data measured after oral and intravenous administration of 10 mg bisoprolol to 12 subjects yielded an absolute bioavailability of 90%. Total and renal clearance were calculated as 15.6 L/hr and 9.6 L/hr, respectively. The volume of distribution was 226 L. Concomitant food intake did not influence the bioavailability of bisoprolol. PMID- 2878940 TI - Susceptibility to multiple sclerosis associated with an immunoglobulin gamma 3 restriction fragment length polymorphism. AB - Susceptibility to multiple sclerosis (MS) has been linked to the immunoglobulin G (Gm) markers as well as HLA-DR genes. We have used a genomic Ig gamma 1 probe which detects polymorphisms in the gamma 1, gamma 2, gamma 3 and pseudogamma genes to identify restriction fragment length polymorphisms associated with MS. A negative association was found between a 5.9-kilobase (kb) Bst EII gamma 3 fragment and MS. Southern blot analysis of genomic DNA revealed the presence of this fragment in 84 of 140 (60.0%) controls, but in only 17 of 59 (28.8%) MS patients. The frequency of the fragment in 47 myasthenia gravis and 16 Graves' disease patients was similar to that in controls, 60.0 and 62.5%, respectively. PMID- 2878942 TI - Absence of response to histamine1 blockade in phencyclidine toxicity. PMID- 2878943 TI - The potentiating effect of restorative pin perforations on periodontal disease. A report of cases. PMID- 2878944 TI - Chemical interventions for pain. PMID- 2878945 TI - A comparison of treatment strategies for clients functionally impaired by extreme shyness and social avoidance. PMID- 2878946 TI - Central alpha 1-adrenergic and opiate systems in the control of the vagal tone in normotensive and spontaneously hypertensive rats. AB - In anesthetized, normotensive beta-blocked rats, the alpha 1-adrenoceptor blocking drug, AR-C 239 (300 micrograms/kg, i.v.) induced a bradycardic effect related to a central increase in the vagal tone. This bradycardia was inhibited by previous administration of naloxone, intravenously (1 mg/kg) or centrally (100 micrograms/kg, i.c.) injected. Naloxone, by itself did not change the heart rate. In brainstem membranes from normotensive rats, AR-C 239 did not influence the stereoselective binding of [3H]naloxone. In spontaneously hypertensive (SH) rats, naloxone peripherally or centrally administered did not influence the activation of the vagal tone induced by AR-C 239, in beta-blocked animals. These results suggest the possible involvement of opiate release in the AR-C 239-induced vagal bradycardia, in normotensive rats. They also afford new arguments for the existence of close interactions between central alpha-adrenergic and opiate systems in the cardiovascular regulation. The possible participation of kappa receptors in this effect is discussed. In addition, such an opiate mechanism triggered by central alpha 1-adrenoceptor blockade seems to be either absent or inactive in SH rats. PMID- 2878947 TI - The immunohistochemical distribution of neuropeptide Y in lumbar pre- and paravertebral sympathetic ganglia of the guinea pig. AB - Neuropeptide Y (NPY)- like immunoreactive nerve cell bodies and nerve fibres have been studied in normal and colchicine-treated ganglia of the caudal lumbar sympathetic chain (LSC) and the inferior mesenteric ganglion (IMG) of the guinea pig. The great majority of noradrenergic ganglion cells in the LSC (defined as containing tyrosine hydroxylase immunoreactivity), but less than 20% of those in the IMG, were NPY-positive. These proportions correspond well to the proportions of neurones that have been found to discharge phasically in electrophysiological experiments on the same ganglia. As noradrenergic terminals innervating blood vessels contain NPY, the data are consistent with the idea that phasic discharge is a characteristic of vasoconstrictor neurones. PMID- 2878948 TI - Short-term beta-adrenergic blockade decreases serum thyroglobulin in hyper- and euthyroid patients. AB - Cardioselective [Acebutolol (N = 10)] or noncardioselective [Oxprenolol (N = 9)] or [Pindolol (N = 9)] beta-adrenergic blockers were given to patients with suspected hyperthyroidism. Four h after start of the beta blockade median serum thyroglobulin (Tg) had decreased to 33 (range: 13-325) micrograms/l from 41 (range: 12-333) micrograms/l before start in the acebutolol treated group (p less than 0.05). A significant decrease in serum Tg was also found in the oxprenolol treated group [before start: 45 (24-423) micrograms/l and after 4h: 43 (18-363) micrograms/l (p less than 0.01)] and in the pindolol-treated group [before start: 154 (33-210) micrograms/l and after 4 h: 63 (19-157) micrograms/l (p less than 0.05) treated groups. After 7 days treatment the decrease in serum Tg was significant [to 85 (34-182) micrograms/l (p less than 0.02)] only in the Pindolol treated group. It is suggested that both hemodynamic changes as well as interference with the intrathyroidal 12 S Tg to 19 S Tg dimerization might explain the changes in serum Tg during beta blockade. Knowledge of drug influence on serum thyroglobulin is important for the interpretation of variations found in patients where thyroglobulin is being used for diagnostic purposes. PMID- 2878949 TI - gamma-Glutamyl transpeptidase in rat liver during 3'-Me-DAB hepatocarcinogenesis: immunohistochemical and enzyme histochemical study. AB - Immunohistochemical localization of gamma-glutamyl transpeptidase (gamma-GTP) in rat liver during 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) hepatocarcinogenesis was investigated and compared with sites of gamma-GTP activity. Immunohistochemically, gamma-GTP was stained in the apical border of proliferating oval cells during the early stages of azo-dye carcinogen feeding. After 7 weeks, multiple hyperplastic nodules appeared in which gamma-GTP was localized in the bile canaliculi. In hepatoma tissues, positive staining for gamma-GTP was observed in the bile canaliculi-like spaces, on the cell membrane, and sometimes in the cytoplasm of malignant cells. Enzyme histochemical staining showed gamma-GTP activity to be present in almost the same areas as the immunoreactive gamma-GTP. However, some areas adjacent to hepatoma tissue showed immunohistochemically reactive protein but no enzyme activity. Immunoreactive gamma-GTP was present in all locations at which enzyme activity was seen. The present data suggest that an altered form of gamma-GTP might be present in tissues during 3'-Me-DAB hepatocarcinogenesis. PMID- 2878950 TI - Heterogeneous distribution of glutamine synthetase during rat liver development. AB - Two days before birth, immunohistochemical detection of glutamine synthetase already reveals a heterogeneous distribution pattern related to the vascular architecture of the liver. Only a small number of hepatocytes in the vicinity of the efferent venules show relatively high staining intensity. Before that age, only megakaryocytes show intense staining, while liver parenchyma is only faintly stained. The developmental profile of glutamine synthetase activity shows two periods of increasing enzyme activity: one in the perinatal period and one in the second and third postnatal week. Both periods are correlated with high levels of circulating corticosteroid hormones. Although the relative number of intensely stained hepatocytes increases during the first rise in enzyme activity, the second rise is correlated with a decreasing number of glutamine synthetase positive hepatocytes which, however, show a considerable increase in staining intensity. Carbamoylphosphate synthetase shows a homogeneous distribution pattern in the perinatal period. Conditions that lead during development to a relatively high level of glutamine synthetase expression in the pericentral compartment apparently originate before the appearance of conditions that lead to a relatively high level of carbamoylphosphate synthetase gene expression in the periportal compartment. Our results indicate that downstream localization of glutamine synthetase in liver acinus is essential from the perinatal period onwards, whereas reciprocal distribution of glutamine synthetase and carbamoylphosphate synthetase gene expression (that is found in adult rat liver) is not. PMID- 2878951 TI - Separate cell types that express two different forms of somatostatin in anglerfish islets can be immunohistochemically differentiated. AB - The somatostatin-related peptides somatostatin-14 (SS-14) and somatostatin-28 (aSS-28) are synthesized at the C-terminal end of two separate pre-pro somatostatins in anglerfish pancreatic islets. The purpose of this study was to determine whether these peptides are expressed in the same or different cell types. Antisera R141 and R293, which recognize the central region of SS-14 and the C-terminal region of aSS-28 ([Tyr7,Gly10] SS-14), respectively, were used in an immunohistochemical examination of anglerfish islets. The R293 antiserum labeled cells were distributed individually or in small clusters. These same cells, as well as a separate set of cells arranged in large clusters, were stained by the R141 antiserum. Pre-absorption of the R141 antiserum with [Tyr7,Gly10] SS-14 eliminated staining by R141 of only those cells also labeled by R293, whereas pre-absorption of R141 with SS-14 prevented all staining. Pre absorption of R293 with [Tyr7,Gly10] SS-14 eliminated all staining, whereas pre absorption with SS-14 had no effect on aSS-28-like immunoreactivity. These results suggest the existence of two separate cell types which express either SS 14 or aSS-28. The cells that contained the somatostatin-related peptides were found to be distinct from those cells that contained insulin, glucagon, or anglerfish peptide Y. However, the cells stained by the R293 antiserum were distributed in close association with glucagon-containing cells. The implications of the existence of separate cell types which express SS-14 or aSS-28 are discussed with regard to processing of the biosynthetic precursors to these peptides. PMID- 2878952 TI - Differential immunolabeling for electron microscopy of diverse peptidergic neurons. AB - We describe a simple and reliable method for differential immunolabeling of pre- and post-synaptic signal peptides at the ultrastructural level. Hypothalamic tissues of rats, including the suprachiasmatic nucleus, were cut on a Vibratome. Visualization of the immunolabeling of somatostatin (SRIH) and vasoactive intestinal polypeptide (VIP) was performed with avidin-biotin-peroxidase diaminobenzidine (DAB). The end product of the DAB to VIP was further silver intensified in a physical processing using silver nitrate, and the silver grains were finally substituted for gold. DAB-labeled SRIH fibers synapse on gold labeled VIP perikarya and dendrites in the suprachiasmatic nucleus. PMID- 2878953 TI - Acute central and renal haemodynamic responses to tertatolol and propranolol in patients with arterial hypertension following head injury. AB - We compared the central and renal haemodynamic effects of tertatolol, a new non cardioselective beta-adrenergic blocking drug without partial agonist activity, with those of an equipotent dosage of propranolol in two groups of 10 patients each with acute cerebral injury who had developed systemic hypertension. After tertatolol, 5 mg orally, mean arterial pressure was unchanged, heart rate decreased by 22% (P less than 0.01) and cardiac index by 24% (P less than 0.01), while renal blood flow remained unchanged (-5%, NS). After 160 mg propranolol orally, mean arterial pressure was unchanged, heart rate decreased by 12% (P less than 0.01), cardiac index by 16% (P less than 0.01) and renal blood flow by 17% (P less than 0.01). There was a moderate rise in norepinephrine levels after tertatolol only. Thus in this particular model of acute hypertension, tertatolol acted as a potent beta-blocking agent but differed from propranolol by preserving renal perfusion. PMID- 2878954 TI - Mild hypokalaemia is not a risk factor in treated hypertensives. AB - The possibility that hypokalaemia might increase the mortality of treated hypertensives in the Glasgow Blood Pressure Clinic has been examined by comparison of serum potassium in decedents and survivors and by calculation of age-adjusted mortality rates for patients grouped in quartiles of serum potassium measured at the last clinic visit. In this study, 3783 patients with non malignant hypertension were followed for an average of 6.5 years and of these 1907 had one or more measurements of serum potassium during their last year of attendance. Serum potassium fell in 414 patients given diuretics with or without other drugs except beta-blockers. This fall was similar in those who died of ischaemic heart disease (3.71 mmol/l) and in those who survived (3.72 mmol/l). Serum potassium rose in 167 patients who received beta-blockers with or without other drugs except diuretics and fell slightly among 1326 patients taking other combinations of drugs. There were no significant differences in serum potassium between decedents and survivors in either of these treatment groups. Age-adjusted mortality in deaths per 1000 patient-years in the lowest quartile of serum potassium (less than 3.7 mmol/l) was 28.1 for men and 15.0 for women. Higher serum potassium was associated with slightly, but not significantly, higher mortality in both sexes. There was no relation between serum potassium and mortality in patients with left ventricular hypertrophy, nor was there a relation when death due to ischaemic heart disease was considered separately. Failure of hypokalaemia to predict outcome was confirmed by univariate and multivariate analyses which included, in addition to potassium, assessment of cigarette smoking, initial blood urea and electrocardiographic findings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878955 TI - Kinin metabolism in human nasal secretions during experimentally induced allergic rhinitis. AB - We have previously shown that both bradykinin and lysylbradykinin are generated in nasal secretions upon nasal challenge of allergic individuals with appropriate allergen and have suggested that these potent pro-inflammatory peptides may contribute to the pathogenesis of the allergic response. In this study we used a variety of synthetic substrates together with both thin layer and high performance liquid chromatography systems to examine the metabolism of these peptides in nasal secretions obtained by lavage. We now demonstrate that in addition to low levels of angiotensin-converting enzyme, nasal lavages contain an aminopeptidase activity that converts lysylbradykinin to bradykinin, and a carboxypeptidase that removes the C-terminal arginine from bradykinin and lysylbradykinin. The levels of all these activities are significantly increased after allergen challenge of allergic, but not nonallergic, individuals. The aminopeptidase and carboxypeptidase activities present in post-challenge lavages from allergic individuals convert lysylbradykinin to intermediate products (bradykinin and des (Arg10) lysylbradykinin) and eventually to des (Arg9) bradykinin. The nasal carboxypeptidase was activated 475% by 0.1 mM CoCl2 and was inhibited by the carboxypeptidase N inhibitor, MERGETPA (D-L-mercaptomethyl-3 guanidino-ethylthiopropanoic acid) (IC50 = 10 microM). The aminopeptidase activity was not affected by MERGETPA but was potently inhibited by amastatin and bestatin (IC50 = 0.05 microM and 3.0 microM, respectively). The activity of the aminopeptidase against its synthetic substrate was also inhibited by lysylbradykinin (IC50 = 50 microM). Both the carboxypeptidase and aminopeptidase activities had neutral pH optima and were inhibited by o-phenanthroline, but were unaffected by inhibitors of neutral endopeptidases (phosphoramidon) or angiotensin-converting enzyme (Captopril). The Km of bradykinin for the nasal carboxypeptidase was 139 +/- 14 microM (n = 3). We conclude that during the allergic response, nasal secretions contain aminopeptidase and carboxypeptidase activities that convert lysylbradykinin and bradykinin (B2 agonists) to des (Arg9) bradykinin (a B1 agonist). Because the nature of the kinin receptors in the nasal mucosa are currently unknown, it remains to be determined whether this metabolism results in the termination of biologic activity or the production of a biologically active moiety. PMID- 2878956 TI - The lpr gene is associated with resistance to engraftment by lymphoid but not erythroid stem cells from normal mice. AB - This study demonstrates cell lineage-specific resistance to engraftment involving lymphocytes but not erythrocytes by the spontaneously autoimmune MRL/lpr mouse strain. In these experiments, MRL/lpr mice were lethally irradiated (1000 R) and reconstituted with normal A-Thy bone marrow stem cells. Periodic analysis from 6 wk to 6 mo posttransplantation demonstrated that the T and B cells of these chimeras were derived from the MRL/lpr host. However, in the same A-Thy--- MRL/lpr chimeras, erythrocyte repopulation was completely of A-Thy donor origin. In contrast, control MRL/+ (congenic mice that differ from MRL/lpr at the lpr locus and do not develop accelerated autoimmune disease) recipients were successfully repopulated in both the lymphoid and erythroid compartments by the A Thy donor cells. PMID- 2878957 TI - Pathogenicity of Clostridium species with other bacteria in mixed infections. AB - The relationship of clostridial isolates with other bacteria in mixed infections was studied by means of a subcutaneous abscess model in mice. We used 26 isolates of seven clostridial species, two Bacteroides spp., eight Gram-positive facultative or anaerobic cocci and three enteric Gram-negative aerobic rods. Abscesses were induced by all seven Clostridium perfringens and three C. butyricum isolates and by some of the others. Selective antimicrobial therapy experiments showed that enteric Gram-negative rods were of equal or greater significance in the formation of abscesses than were clostridial strains in mixed infections. Enhancement or suppression of each component of the mixed infection was studied by comparing the number of each bacterium to its number when injected alone. Enhancement was observed mainly with C. perfringens in mixed infections. By contrast, other Clostridium spp. were less able to induce enhancement. Clostridium difficile and C. sporogenes often inhibited other bacterial species. This study demonstrated the synergistic and antagonistic relationship between clostridial species and other bacteria. PMID- 2878958 TI - [Spontaneous rupture of the kidney. Apropos of a case of Kussmaul-Meier panarteritis nodosa]. AB - A patient with periarteritis nodosa presented with purely intra-abdominal visceral manifestations. This form of the affection, in the absence of subcutaneous granulomas allowing histologic examination, can be revealed only by celiac and renal angiography, results being pathognomonic. As a function of the organ involved the clinical picture can be dramatic, with rupture of parenchymatous organs affecting vital prognosis and requiring immediate surgery. PMID- 2878959 TI - Response of carcinogen-altered mouse epidermal cells to phorbol ester tumor promoters and calcium. AB - Primary cultures of mouse epidermal cells are induced to terminally differentiate when extracellular calcium levels are increased to more than 0.1 mM. After carcinogen treatment, cellular foci can be selected that resist this calcium signal to terminally differentiate. Calcium causes these foci to stratify; however, in contrast to normal epidermis, DNA-synthesizing cells in these foci are found in the suprabasal cell layers as well as in basal cells. Cell lines derived from these foci may be considered to be putative initiated cells. Three of these cell lines, designated 308, D, and F, have been characterized for their response to calcium and phorbol ester tumor promoters. The formation of cornified cells and the activity of epidermal transglutaminase were utilized as markers of epidermal differentiation. Neither calcium nor the tumor promoter 12-O tetradecanoylphorbol-13-acetate (TPA) increased transglutaminase activity or cornification of any of the 3 lines. Proliferation was estimated by the [3H]thymidine labeling index, by incorporation of [3H]thymidine into DNA, and by a clonal growth assay. Unlike primary normal cultures, raising the calcium level of the medium did not markedly reduce the rate of proliferation of any of the 3 cell lines. In 2 of the lines, line 308 and line D, proliferation increased in response to TPA exposure. In line F, [3H]thymidine incorporation in confluent cultures was inhibited by TPA, while in cells plated at clonal densities, TPA was cytotoxic at doses of 5 ng/ml or higher. If these calcium-resistant epidermal cell lines correspond to initiated cells, their lack of sensitivity to the induction of terminal differentiation by TPA could account for their growth relative to normal cells. Those lines that also respond to stimulation of proliferation by TPA to a greater extent than normal cells would have a further growth advantage. PMID- 2878960 TI - [Immunohistochemical studies of fetal and maternal endocrine pancreases during pregnancy and the puerperium in streptozotocin-induced diabetic rats]. AB - In order to clarify the influence of the diabetic state on the structure of maternal and fetal endocrine pancreases, the distribution of alpha, beta and delta cells in the islets of Langerhans (IL) was investigated by PAP methods in normal and streptozotocin (STZ)-induced diabetic rats. The size of the IL significantly increased during pregnancy and on day 14 of puerperium in normal and diabetic maternal rats. The total cell numbers of IL also increased during pregnancy but decreased in puerperium in both groups. Although the number of beta cells was reduced in STZ-treated rats, they could increase during pregnancy as in the normal group. The number of beta cells kept increasing in puerperium in the diabetic group, but not in the normal group. The number of alpha and delta cells in diabetic rats was greater than in normal rats but did not change remarkably during pregnancy and in puerperium. The IL of fetuses from diabetic mothers were slightly greater in size and number than those from normal mothers. The number of fetal beta cells from normal mothers was somewhat greater than that from diabetic mothers. The number of fetal alpha and delta cells from diabetic mothers was slightly greater than that from normal mothers. These findings, therefore, suggest that diabetic IL could adapt themselves to pregnancy-induced metabolic changes. PMID- 2878961 TI - [An autopsy case of polyarteritis nodosa associated with multiple cranial neuritis and thrombotic thrombocytopenic purpura]. PMID- 2878962 TI - Effects of aldosterone on rat collecting tubule N-ethylmaleimide-sensitive adenosine triphosphatase. AB - Acidification in the collecting tubule is thought to be mediated by a proton translocating adenosine triphosphatase (ATPase), and is modulated by aldosterone. Using an enzymatic microassay, we measured N-ethylmaleimide (NEM)-sensitive ATPase activity in isolated tubules obtained from control rats and rats receiving aldosterone by osmotic minipumps (5 micrograms/100 gm/day for 7 days). In control animals, enzyme activity was higher in cortical than in outer medullary collecting tubules (259 +/- 36 vs. 111 +/- 16 pmol/mm/hr, P less than 0.005, respectively). Prolonged aldosterone administration resulted in an increase in enzyme activity in the outer medullary collecting tubule (274 +/- 39 pmol/mm/hr, P less than 0.005), with no change in the cortical collecting tubule (255 +/- 47 pmol/mm/hr). These findings suggest that prolonged enhancement of acidification by mineralocorticoids is mediated by different mechanisms in the two segments of the rat collecting tubule. Whereas in the outer medullary segment an increase in the activity of NEM-sensitive ATPase facilitates the chronic enhancement in acidification, high basal enzyme activity in the cortical segment and institution of favorable voltage condition by mineralocorticoid treatment may obviate the need to increase enzyme activity. PMID- 2878963 TI - Cholinergic agonist and antagonist drugs modulate the growth hormone response to growth hormone-releasing hormone in the rat: evidence for mediation by somatostatin. AB - Recently, data have been presented showing that muscarinic cholinergic agonists or antagonists can modulate, in opposite ways, GH-releasing hormone GHRH)-induced GH release in man. The aim of the present study was, first, to confirm these findings in the rat and, secondly, if confirmed, to investigate the mechanism(s) subserving the effect of cholinergic drugs. In adult male rats bearing chronic indwelling atrial cannulae, pretreatment with the cholinergic antagonists pirenzepine (0.5 mg/kg, i.v.) or atropine (0.5 mg/kg, i.v.) significantly reduced the rise in plasma GH induced by GHRH (2 micrograms/kg, i.v.), while pretreatment with the cholinergic agonist pilocarpine (3 mg/kg, i.v.) potentiated it. In rats with hypothalamic somatostatin (SRIF) depletion, i.e. rats with anterolateral deafferentation of the mediobasal hypothalamus or rats treated with cysteamine, the modulatory action of cholinergic drugs on the neuroendocrine effect of GHRH was completely lacking. In these two experimental models, an antiserum raised against SRIF failed to elicit a rise in plasma GH and measurement of hypothalamic SRIF content revealed a clear-cut reduction of the neuropeptide. Atropine (1 mumol/l) and pilocarpine (1 mumol/l), added to pituitary cells in vitro, failed to alter GHRH-induced GH release. The present results indicate that muscarinic cholinergic agonists and antagonists modulate GHRH-induced GH release in the rat and suggest that the effect of cholinergic modulation takes place through SRIF. PMID- 2878964 TI - Impact of symbiotic algae on sea anemone metabolism: analysis by in vivo 31P nuclear magnetic resonance spectroscopy. AB - High-field pulsed Fourier-transform nuclear magnetic resonance spectroscopy (NMR) was used to quantify the adenylate levels of sea anemones (Aiptasia pulchella) with and without symbiotic dinoflagellates (Symbiodinium sp.). Animals were fed to repletion, then starved in darkness for up to six days before collection of in vivo NMR spectra. The host adenylate ratio of ATP: (ATP + ADP) declined significantly with increasing periods of starvation in both symbiotic and aposymbiotic hosts (P less than 0.05). However, the decline in the animal adenylate ratio was significantly more rapid in animals bearing symbiotic algae (P less than 0.05). This suggests that symbiotic algae in darkness cause more rapid depletion of host energy reserves, possibly by drawing on host pools of organic substrates. In vivo NMR spectroscopy was also used to evaluate the effect on A. pulchella of photosynthesis by zooxanthellae. Symbiotic anemones were fed to repletion, then starved under high irradiance (300 to 320 mu Ein m-2 s-1) or low irradiance (70 to 80 mu Ein m-2 s-1) conditions for up to five days. The host adenylate ratio declined significantly (P less than 0.01) with starvation under both treatments, but no significant difference was detected between treatments (P greater than 0.35). Blotted wet weight of anemones under high and low irradiance declined by 50% over eight days of starvation, but there was no significant difference in the rate of weight loss by anemones in the two treatments. There results suggest that translocation of photosynthate from symbiotic zooxanthellae does not significantly affect host adenylate ratio or have a sparing effect on host biomass during starvation in this symbiotic sea anemone. PMID- 2878965 TI - TSH receptor antibody in autoimmune thyroiditis and its clinical significance. PMID- 2878966 TI - The transfer of genes encoding production of mannose-resistant haemagglutinating fimbriae from uropathogenic enterobacteria. AB - Two hundred and thirty-seven bacterial strains, isolated from patients with urinary tract infections, were examined for the presence of plasmid-determined fimbrial adhesins. Ninety-nine strains were capable of producing mannose resistant haemagglutination. Seventeen of these strains possessed transferable resistance plasmids and 11 of these were also able to transfer the mannose resistant haemagglutination gene, suggesting that it was carried on the R plasmid or had been mobilized by it. PMID- 2878967 TI - Variation in the expression of pili and outer membrane protein by Neisseria meningitidis during the course of meningococcal infection. AB - The occurrence of antigenic shift during meningococcal infection has been investigated by comparison of paired isolates obtained from the blood, cerebrospinal fluid or nasopharynx of patients. Isolates from any individual produced identical DNA 'fingerprints' and showed stability in expression of both class 2 outer membrane protein and an antigen common to pathogenic Neisseria, confirming their origin as a single strain. One of the four strains examined produced variants which differed in the molecular mass of their class 5 outer membrane proteins. Three of the strains produced pili containing the epitope recognized by monoclonal antibody SM1 and two of these gave rise to variants which expressed pili of differing subunit molecular masses. The two variants of the remaining strain produced pilins lacking the common epitope detected by antibody SM1 but radioimmune precipitation with polyclonal anti-pilus antiserum revealed that variation in the molecular mass of the pilin expressed also occurred with this second class of pili. Antigenic variation in expression of both class 5 outer membrane proteins and pili therefore appears to be a common occurrence during meningococcal infection. PMID- 2878968 TI - Effects of immune colostrum on the expression of a K88 plasmid encoded determinant: role of plasmid stability and influence of phenotypic expression of K88 fimbriae. AB - Passaging of the K88-positive Escherichia coli strain CN6913 through synthetic medium containing immune colostrum gave rise to large numbers of K88-negative CN6913 variants. These K88-negative variants had all lost a single large plasmid known to encode the K88 genetic determinant. Four other large plasmids harboured by this strain were unaffected. Viable K88-positive and K88-negative variants of CN6913 accumulated at a similar rate in synthetic medium and in medium containing non-immune colostrum. In the presence of immune colostrum, viable cells of the K88-negative variant accumulated faster and to a greater extent in cultures than the K88-positive variant if incubated at 37 degrees C, which favours the phenotypic expression of K88. However, when similar cultures were incubated at 18 degrees C, a temperature known to inhibit phenotypic expression of K88, the accumulation of viable cells of the two variants was strictly comparable in all media and no loss of plasmid or increase in K88-negative variants was observed. Cells containing a pBR322-based K88-encoding recombinant plasmid were also eliminated by immune colostrum whereas cells containing pBR322 were not. Plasmids encoding the K99 antigen were not readily eliminated from strains passaged through medium containing immune colostrum. K99-negative variants that were detected still harboured the K99-encoding plasmid. PMID- 2878969 TI - Characterization and cloning of two Rhizobium leguminosarum genes coding for glutamine synthetase activities. AB - We have demonstrated that Rhizobium leguminosarum strain LPR1105 contains a heat stable and a heat labile glutamine synthetase (EC 6.3.1.2) activity similar to those described for other Rhizobiaceae. Most of the activity is heat stable when this strain is grown on glutamine as sole nitrogen source, but most is heat labile when grown on nitrate. Using a gene bank of R. leguminosarum DNA we have isolated two clones, which code for heat stable (p7D9) and heat labile (p4F7) glutamine synthetase activity, by complementing the glutamine auxotrophy of Klebsiella pneumoniae glnA mutants. Cross-hybridization of p7D9 with a fragment of the glnA gene of K. pneumoniae was observed, but no cross-hybridization between p7D9 and p4F7 was found. Since these two regions hybridize to genomic DNA of R. leguminosarum they are probably the structural genes for GSI and GSII, and the availability of these genes will make it possible to test this hypothesis. Clone p4F7 complements an ntrC+ but not an ntrC K. pneumoniae glnA mutant, suggesting that the ntrC gene is required for the complementation of the glutamine auxotrophy by this plasmid. PMID- 2878970 TI - Characterization of messenger RNAs of measles virus. AB - Ten different RNA species associated with measles virus were detected in virus infected cells. The largest RNA (no. 1) was considered to be genomic RNA and the other nine RNAs were found to have a methylated cap as well as a poly(A) tail. Northern blot hybridization indicated that RNAs no. 2 and 7 to 10 correspond to mRNAs encoding structural proteins, and that RNAs no. 3 to 6 are intermediate sized (IS)RNAs. The possibility that the ISRNAs represent defective interfering RNA or a precursor form of the mRNA seems to be unlikely since the amounts of IS RNAs did not increase after undiluted passages or decrease in a pulse-chase experiment. These results indicate that IS RNAs are readthrough transcripts of neighbouring cistrons. PMID- 2878971 TI - Persistent infection of rats with haemorrhagic fever with renal syndrome virus and their antibody responses. AB - Newborn (within 24 h after birth), 1-week-old and 6-week-old (adult) rats were inoculated with a Hantaan-related virus (B-1) and attempts were made to isolate the virus from various organs. Virus-specific antigens were detected in various organs of newborn rats. Moreover virus could be isolated from almost all their organs even 25 weeks after infection. In contrast, in rats infected at 6 weeks of age the virus could be isolated from various organs but its concentration decreased progressively with time. The levels of haemagglutination-inhibiting (HI) and neutralizing antibodies to B-1 virus in the sera were measured. In adult rats, HI antibodies were first detected 2 weeks after infection and their titre rose to a maximum after 5 weeks. On the other hand, in newborn rats the levels of antibodies remained low until 5 or 6 weeks after infection and started to increase to a high level more than 9 weeks after infection. Furthermore, in rats infected soon after birth IgM antibodies predominated for a long time and these antibodies also neutralized infectivity at a high level. These data suggest that the induction of a high titre of neutralizing antibodies mainly of the IgM type does not result in virus clearance in newborn rats and that cellular immunity may be important for virus clearance in vivo. PMID- 2878972 TI - Abundance in the embryonic brainstem of adrenaline during the absence of detectable tyrosine hydroxylase activity. AB - The activities of the catecholamine synthetic enzymes tyrosine hydroxylase and phenylethanolamine N-methyltransferase, and the concentrations of the catecholamines and their respective metabolites, have been measured in the dorsal and ventral halves of the brainstem at various ages in the embryonic and adult rat. The activity of phenylethanolamine N-methyltransferase in both parts of the brainstem at day 14 of gestation is at or greater than adult levels and thereafter displays relatively small variations during ontogeny. Tyrosine hydroxylase activity, in contrast, is undetectable at day 14 and increases slowly, achieving only 20-25% of adult values by day 18 of gestation. Adrenaline concentrations correlate well with the activity of phenylethanolamine N methyltransferase, showing a precocious development, whereas noradrenaline and 3,4-dihydroxyphenylethylamine (dopamine) concentrations are more closely related to the enhancement of tyrosine hydroxylase activity; at day 18 of gestation, for example, they are only 5 and 10%, respectively, of the adult values. The concentrations of the metabolites of noradrenaline and dopamine are suggestive of a high rate of turnover. These results confirm previous immunocytochemical evidence of a tardy appearance of tyrosine hydroxylase-like immunoreactivity in the phenylethanolamine N-methyltransferase-positive perikarya of the embryonic medulla oblongata. In addition, the abundance of adrenaline in this area at early gestational stages strongly suggests that, despite the paucity of tyrosine hydroxylase, phenylethanolamine N-methyltransferase is active in vivo and is utilizing a substrate other than noradrenaline. It is likely, however, that at later stages of gestation, when tyrosine hydroxylase is present at sufficient activity to supply noradrenaline, the conventional synthetic pathway for adrenaline formation comes into being. PMID- 2878973 TI - Activation of tyrosine hydroxylase in PC12 cells by the cyclic GMP and cyclic AMP second messenger systems. AB - Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, is subject to regulation by a variety of agents. Previous workers have found that cyclic AMP-dependent protein kinase and calcium-stimulated protein kinases activate tyrosine hydroxylase. We wanted to determine whether cyclic GMP might also be involved in the regulation of tyrosine hydroxylase activity. We found that treatment of rat PC12 cells with sodium nitroprusside (an activator of guanylate cyclase), 8-bromocyclic GMP, forskolin (an activator of adenylate cyclase), and 8-bromocyclic AMP all produced an increase in tyrosine hydroxylase activity measured in vitro or an increased conversion of [14C]tyrosine to labeled catecholamine in situ. Sodium nitroprusside also increased the relative synthesis of cyclic GMP in these cells. In the presence of MgATP, both cyclic GMP and cyclic AMP increased tyrosine hydroxylase activity in PC12 cell extracts. The heat-stable cyclic AMP-dependent protein kinase inhibitor failed to attenuate the activation produced in the presence of cyclic GMP. It eliminated the activation produced in the presence of cyclic AMP. Sodium nitroprusside also increased tyrosine hydroxylase activity in vitro in rat corpus striatal synaptosomes and bovine adrenal chromaffin cells. In all cases, the cyclic AMP-dependent activation of tyrosine hydroxylase was greater than that of the cyclic GMP dependent second messenger system. These results indicate that both cyclic GMP and cyclic AMP and their cognate protein kinases activate tyrosine hydroxylase activity in PC12 cells. PMID- 2878974 TI - Synaptosomal membrane-bound form of endopeptidase-24.15 generates Leu-enkephalin from dynorphin1-8, alpha- and beta-neoendorphin, and Met-enkephalin from Met enkephalin-Arg6-Gly7-Leu8. AB - Brain contains a membrane-bound form of endopeptidase-24.15, a metalloendopeptidase predominantly associated with the soluble protein fraction of brain homogenates. Subcellular fractionation of the enzyme in rat brain showed that 20-25% of the total activity is associated with membrane fractions including synaptosomes. Solubilization of the enzyme from synaptosomal membranes required the use of detergents or treatment with trypsin. The specific activity of the enzyme in synaptosomal membranes measured with tertiary-butoxycarbonyl-Phe-Ala Ala-Phe-p-aminobenzoate as substrate was higher than that of endopeptidase-24.11 ("enkephalinase"), a membrane-bound zinc-metalloendopeptidase believed to function in brain neuropeptide metabolism. Purified synaptosomal membranes converted efficiently dynorphin1-8, alpha- and beta-neoendorphin into leucine enkephalin and methionine-enkephalin-Arg6-Gly7-Leu8 into methionine enkephalin in the presence of captopril, bestatin, and N-[1-(R,S)-carboxy-2-phenylethyl]-Phe-p aminobenzoate, inhibitors of angiotensin converting enzyme (EC 3.4.15.1), aminopeptidase (EC 3.4.11.2), and membrane-bound metalloendopeptidase (EC 3.4.24.11), respectively. The conversion of enkephalin-containing peptides into enkephalins was virtually completely inhibited by N-[1-(R,S)-carboxy-2 phenylethyl]-Ala-Ala-Phe-p-aminobenzoate, a specific active-site-directed inhibitor of endopeptidase-24.15, indicating that this enzyme was responsible for the observed interconversions. The data indicate that synaptosomal membranes contain enzymes that can potentially generate and degrade both leucine- and methionine-enkephalin. PMID- 2878975 TI - Cellular origins of cyclic GMP responses to excitatory amino acid receptor agonists in rat cerebellum in vitro. AB - Incubated slices and freshly dissociated cells from 8-day-old rat cerebellum were used to try to identify the cells that participate in the large increases in cyclic GMP levels that follow activation of excitatory amino acid receptors in this tissue. In the slices, cyclic GMP responses to L-glutamate and related excitants were unaffected by tetrodotoxin and could be replicated by the guanylate cyclase activator nitroprusside. Nitroprusside and the receptor agonists appeared to activate the same pool of the enzyme. Prior destruction of neuroblasts, deep nuclei, or Golgi neurones did not cause loss of responses to L glutamate. If granule cells were rendered necrotic, however, the cyclic GMP responses to all excitants tested were reduced by greater than or equal to 90%. Substantial losses of responses to veratridine and high K+ levels also occurred, but the nitroprusside-induced elevations were unaffected. In dissociated cell suspensions, the magnitude of responses to receptor agonists, but not those to nitroprusside, was markedly dependent on cell concentration. Responses to L glutamate were the same in cell suspensions that were Purkinje cell depleted and Purkinje cell enriched. It is concluded that granule cells are primarily involved in the cyclic GMP responses to excitatory amino acids but that the cyclic GMP accumulations occur elsewhere, probably in glial cells. PMID- 2878976 TI - Brain galactolipid content in a patient with pseudoarylsulfatase A deficiency and coincidental diffuse disseminated sclerosis, and in patients with metachromatic, adreno-, and other leukodystrophies. AB - A 4-year old boy died of diffuse disseminated sclerosis (DDS) of the brain and was found to have also pseudoarylsulfatase A deficiency (PASAD) with about 20% residual arylsulfatase A (ASA) and cerebroside sulfatase (CS) activity. The reexamination of lipids did not show any sulfatide accumulation in the patient's organ extracts. Although the residual CS activity in the patient's extracts was clearly demonstrable only after partial purification, it was concluded that this activity protects organ tissues from sulfatide accumulation in PASAD, since in sulfatide lipidosis (metachromatic leukodystrophy, MLD) no residual CS activity was detectable. The study of residual ASA activity in the patient's fibroblasts by gel electrofocusing resulted in an almost normal enzyme microheterogeneity. However, the detailed study of the brain galactolipids in the patient revealed an elevated ratio of sulfatide/galactocerebroside content, despite the decrease of both lipids. In tissues of other patients with severe demyelinating diseases different from DDS and MLD, this galactolipid ratio was also found to be increased, especially in three patients with adrenoleukodystrophy. A general mechanism of this anomaly in severe demyelination is considered. PMID- 2878977 TI - Rapid inactivation of brain glutamate decarboxylase by aspartate. AB - In the absence of its cofactor, pyridoxal 5'-phosphate (pyridoxal-P), glutamate decarboxylase is rapidly inactivated by aspartate. Inactivation is a first-order process and the apparent rate constant is a simple saturation function of the concentration of aspartate. For the beta-form of the enzyme, the concentration of aspartate giving the half-maximal rate of inactivation is 6.1 +/- 1.3 mM and the maximal apparent rate constant is 1.02 +/- 0.09 min-1, which corresponds to a half-time of inactivation of 41 s. The rate of inactivation by aspartate is about 25 times faster than inactivation by glutamate or gamma-aminobutyric acid (GABA). Inactivation is accompanied by a rapid conversion of holoenzyme to apoenzyme and is opposed by pyridoxal-P, suggesting that inactivation results from an alternative transamination of aspartate catalyzed by the enzyme, as previously observed with glutamate and GABA. Consistent with this mechanism pyridoxamine 5' phosphate, an expected transamination product, was formed when the enzyme was incubated with aspartate and pyridoxal-P. The rate of transamination relative to the rate of decarboxylation was much greater for aspartate than for glutamate. Apoenzyme formed by transamination of aspartate was reactivated with pyridoxal-P. In view of the high rate of inactivation, aspartate may affect the level of apoenzyme in brain. PMID- 2878978 TI - Effects of alpha 2-adrenergic agonists and antagonists on photoreceptor membrane currents. AB - Type B photoreceptors of the nudibranch mollusc Hermissenda crassicornis receive excitatory synaptic potentials (EPSPs) whose frequency is controlled by potential changes of a neighboring cell known as the S optic ganglion cell which is thought to be electrically coupled to the presynaptic source of these EPSPs, the E optic ganglion cell. The frequency of the EPSPs increases when a conditioned stimulus (light) is paired with an unconditioned stimulus (rotation) during acquisition of a Pavlovian conditioned response. The results of the present study are consistent with an adrenergic origin for these EPSPs. Noradrenergic agonists (greater than 100 microM), norepinephrine and clonidine, only slightly depolarize the type B cell but clearly prolong its depolarizing response to light. Serotonin, by contrast, causes hyperpolarization of the type B cell's resting potential as well as after a light step. Clonidine reduces voltage-dependent outward K+ currents (IA, an early current, ICa2+-K+, a late Ca2+-dependent current) that control the type B cell's excitability (and thus its light response and membrane potential). These effects of clonidine are reduced or blocked by the alpha 2-receptor antagonist, yohimbine (0.5 microM), but not the alpha 1-blocker, prazosin. The same yohimbine concentration also blocked depolarizing synaptic excitation of the type B cell in response to depolarization of a simultaneously impaled S optic ganglion cell. Histochemical techniques (both the glyoxylic acid method of de la Torre and Surgeon and the formaldehyde-induced fluorescence or Falck-Hillarp method) demonstrated the presence of a biogenic amine(s) within a single neuron in each optic ganglion as well as three or four cells within the vicinity of previously identified visual interneurons. No serotonergic neurons were found within the optic ganglion or in proximity to visual interneurons. A clonidine like synaptic effect on type B cells, therefore, could amplify conditioning specific changes of membrane currents by increasing type B depolarization and possibly, as well, by elevating intracellular second messengers. PMID- 2878979 TI - Relationship between dopamine receptor occupation by spiperone and acetylcholine levels in the rat striatum after long-term haloperidol treatment depends on dopamine innervation. AB - The effect of chronic neuroleptic treatment on the relationship between the blockade of dopamine (DA) receptors by the neuroleptic drug spiperone and the decline in acetylcholine (ACh) levels was determined in the rat striatum in vivo. In rats, a unilateral lesion of the nigrostriatal pathway was produced with 6 hydroxydopamine. The rats were treated for 6 weeks with haloperidol (twice a day at 1 mg kg-1). Partial and complete receptor occupation was determined with radioactive spiperone (a D2 antagonist), given in various doses of different specific activity 2 h before death. ACh, choline, and radioactivity contents were measured in the same striatum. Following long-term haloperidol treatment, an increase in the maximal number of binding sites for spiperone was found. Virtually identical negative (linear) correlations between striatal ACh content and the number of receptors occupied by spiperone were found in saline- or subchronic haloperidol-treated rats when DA innervation was intact. The slope of the line describing the decrease in ACh content per occupied receptor, however, was much lower in haloperidol-treated rats than in saline-treated animals. After lesioning of the dopaminergic pathway, there was no longer a correlation between the receptor occupation and ACh levels in the striatum. These results show that receptor occupation by a neuroleptic correlates highly with function only when dopaminergic innervation is intact. Also, it appears that there is no fixed number of striatal ACh molecules per DA receptor, and, finally, that in vivo receptor detection methods distinguish differences in receptor density (as do in vitro techniques). PMID- 2878980 TI - Dementia of the Alzheimer's type: changes in hippocampal L-[3H]glutamate binding. AB - Glutamate or a related excitatory amino acid is thought to be the major excitatory neurotransmitter of hippocampal afferents, intrinsic neurons, and efferents. We have used an autoradiographic technique to investigate the status of excitatory amino acid receptors in the hippocampal formation of patients dying with dementia of the Alzheimer type (DAT). We examined L-[3H]glutamate binding to sections from the hippocampal formation of six patients dying of DAT and six patients without DAT and found marked reductions in total [3H]glutamate binding in all regions of hippocampus and adjacent parahippocampal cortex in DAT brains as compared to controls. When subtypes of excitatory amino acid receptors were assayed, it was found that binding to the N-methyl-D-aspartate (NMDA)-sensitive receptor was reduced by 75-87%, with the greatest loss found in stratum moleculare and stratum pyramidale of CA1. Binding to quisqualate (QA)-sensitive receptors was reduced by 45-69%. There were smaller reductions (21-46%) in GABAA receptors in DAT cases. Muscarinic cholinergic receptors assayed in adjacent sections of hippocampal formation were unchanged in DAT. Benzodiazepine receptors were reduced significantly only in parahippocampal cortex by 44%. These results suggest that glutamatergic neurotransmission within the hippocampal formation is likely to be severely impaired in Alzheimer's disease. Such impairment may account for some of the cognitive decline and memory deficits that characterize DAT. PMID- 2878981 TI - Heterogeneity of a cultured neoplastic glial line. Establishment and characterisation of six clones. AB - Six clones have been established from a tumorigenic glial cell line (VMDk P497) originally derived from a spontaneous mouse astrocytoma. The clones express dissimilar morphological, antigenic, kinetic and chromosomal properties, thereby indicating the heterogeneity of the parent culture line. PMID- 2878982 TI - Hypertension, antihypertensive drugs, and atherogenesis. Mechanisms and clinical implications. AB - This paper briefly reviews the current knowledge regarding the effects of hypertension and of antihypertensive drugs on the arterial wall and their possible influence on atherogenesis. The potential clinical implications of the experimental data are discussed, and the following recommendations are made regarding therapy of the hypertensive patient: 1) Management of associated hyperlipoproteinemia, even if mild, would appear to be essential in the hypertensive patient because hypertension does not appear to promote atherosclerosis appreciably when plasma cholesterol levels are low. 2) In the mild hypertensive with diastolic blood pressure from 90-95 mmHg without associated target-organ damage or other major risk factors, treatment of the hypertension should primarily be nonpharmacologic in nature. 3) Hypertensive subjects receiving antihypertensive drugs that can have an adverse effect on plasma lipoproteins should have plasma lipids monitored closely; if unfavorable effects occur, revision of therapy should be considered. 4) Major attempts should be made to reduce other risk factors as well, particularly smoking. 5) Because of inherent difficulties in reversing atherosclerosis, treatment of hypertension and other abnormal risk factors should be instituted early in life before severe disease has developed. Finally, research efforts should intensified to delineate the mechanisms by which hypertension and antihypertensive drugs affect the arterial wall and to develop new approaches for protection against arterial injury. PMID- 2878983 TI - Neuropeptides as regulators of consummatory behaviors. AB - The control of ingestive behavior involves a variety of neurotransmitters, including monoamines, peptides and amino acids. For the past decade many investigators have focused their research on the role that regulatory peptides play in eating behavior. Many peptides, including cholecystokinin, bombesin, calcitonin, corticotropin-releasing factor, neurotensin and somatostatin, have been reported to decrease the amount of food ingested by laboratory animals. In contrast, a relatively small number of peptides increase food intake. The present review describes the effects of these peptides on consummatory behaviors in various species and their sites of action. PMID- 2878984 TI - Folinic acid therapy in treatment of dihydropteridine reductase deficiency. AB - We gave folinic acid to three siblings, and to a fourth child, who have or had dihydropteridine reductase (DHPR) deficiency. The youngest began folinic acid therapy in addition to neurotransmitter precursors and a phenylalanine-restricted diet at age 2 months, and at 2 years of age has near normal development without evidence of neurologic impairment. His older brother began similar treatment at 5 1/2 months of age, when early neurologic findings were evident. At age 6 years his mental retardation and neurologic impairment are less severe than reported in most patients with DHPR deficiency. Little improvement occurred in their sister, who first received treatment at 2 years of age, when she already had severe neurologic impairment. An unrelated boy with profound neurologic impairment showed subtle signs of improvement after he began treatment with folinic acid alone at age 9 years. These results provide evidence that folinic acid is important in the treatment of DHPR deficiency and, if begun early in infancy, may prevent irreversible neurologic damage. The mechanism of folinic acid action in DHPR deficiency may be to increase indirectly the synthesis of 5 methyltetrahydrofolate. PMID- 2878985 TI - Correlation between polymorphic DNA haplotypes at phenylalanine hydroxylase locus and clinical phenotypes of phenylketonuria. AB - Eight polymorphic sites for seven restriction endonucleases have been reported at the human phenylalanine hydroxylase locus. The composite profile of the presence or absence for each of the eight polymorphic sites within an allele defines the haplotype of the corresponding allele. Twelve such haplotypes associated with normal and mutant phenylalanine hydroxylase alleles have been identified in 33 Danish families with children with phenylketonuria. Of the 66 mutant alleles analyzed, 59 (89%) were associated with only four haplotypes. The identification of individual phenylalanine hydroxylase alleles by haplotype analysis enables correlation of the hyperphenylalaninemic phenotypes of the patients with their genotypes. Patients who were either homozygous or heterozygous for the mutant alleles of haplotypes 2 and 3 had a severe clinical course. Patients who had a mutant allele of either haplotype 1 or 4 usually had a less severe clinical phenotype. The recent demonstration that the mutation responsible for classic phenylketonuria associated with haplotype 3 is not present in mutant alleles of other haplotypes provides unambiguous evidence that there are multiple mutations in the phenylalanine hydroxylase gene and supports the hypothesis that different combinations of mutant alleles may be responsible for the clinical diversity of phenylketonuria. PMID- 2878986 TI - Cutaneous polyarteritis nodosa in a patient with ulcerative colitis. AB - Skin disease is common in patients with inflammatory bowel disease. Described herein is a child with ulcerative colitis and cutaneous polyarteritis nodosa. Review of the literature suggests cutaneous polyarteritis must be considered as another skin lesion associated with inflammatory bowel disease. Cutaneous polyarteritis tends to run a chronic relapsing course independent of bowel disease, however. PMID- 2878987 TI - Zollinger-Ellison syndrome associated with a renal gastrinoma in a child. AB - Renal gastrinoma has not been previously reported. A 12-year-old boy with Zollinger-Ellison syndrome was found to have a renal tumor. No other tumor was detectable by imaging techniques, and selective venous sampling for gastrin showed a significant renal vein to vena cava gradient. Nephrectomy was performed, and examination of the tumor showed typical histologic features of an endocrine tumor. G cells were apparent by electron microscopy, and immunoperoxidase staining for gastrin, neuron-specific enolase, and chromogranin were positive. The gastrin content was unusually low for gastrinomas: 128 pg/g. Following nephrectomy, fasting gastrin and secretin stimulation testing were normal. Basal acidity was reduced by 60% but remained elevated at 39 mmol H +/h (hydrogen ion per hour). We speculate that renal gastrinoma may be characterized by uniquely poor gastrin storage and that curative resection of all gastrinoma tissue may not necessarily be associated with immediate complete suppression of hyperacidity. PMID- 2878988 TI - Results of early thyroidectomy for medullary thyroid carcinoma in children with multiple endocrine neoplasia type 2. AB - Children with multiple endocrine neoplasia type 2 (MEN2) often develop medullary carcinoma of the thyroid (MCT) or its precursor, C-cell hyperplasia. Survival results are improved if malignancy is diagnosed early from the results of plasma immunoreactive calcitonin (iCT) measurement. The effect of early detection and thyroidectomy in children with MEN2 syndrome was determined by reviewing the experience between 1975 and 1985. Seventeen children with MEN2 who were 12 years old or younger underwent a total thyroidectomy for MCT or C-cell hyperplasia. iCT was measured in all patients preoperatively and postoperatively. Of the 17 children, 14 (82%) had MEN2a and 3 (18%) had MEN2b. There were 14 (82%) female and three (18%) male patients; their mean age was 6.97 years (range 1.5 to 12 years). In all patients, the diagnosis of MCT was made from initial elevated levels of iCT after stimulation with pentagastrin. Three patients had clinical evidence of disease preoperatively. All patients underwent a total thyroidectomy and lymph nodes were removed from the central zone; a neck dissection was performed in the three with clinically obvious disease. MCT with C-cell hyperplasia was found in 11 children and C-cell hyperplasia alone in six. Of the 11 with carcinoma, eight had bilateral disease and three unilateral. Six children had bilateral C-cell hyperplasia. All 17 children were alive and feeling well at the time of this report; however, three had evidence of metastatic disease according to iCT measurements. None of the children had recurrent nerve injuries; one had evidence of hypoparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2878989 TI - A vacuum microbalance technique for studies on the wettability of powders. AB - A vacuum microbalance technique has been used to evaluate the wettability of powders. The rate of uptake, and equilibrium weight of uptake, of water vapour onto outgassed powder samples, of differing wettabilities, were determined at different known temperatures. Standard techniques of data analysis were used to establish the enthalpy, entropy and Gibb's free energy of the activation and adsorption processes. The values obtained appeared to be in the correct order of magnitude and those for activation clearly reflected the relative wettability of the powders. Tests for compensation demonstrated that with the exception of phenobarbitone, there was probably a common mechanism producing the adsorption. PMID- 2878990 TI - Pharmacokinetics of intravenously administered glutathione in the rat. AB - By means of an open two compartment model with a distribution and elimination phase, the pharmacokinetic properties of intravenously administered GSH (reduced glutathione) have been investigated in the rat. After a bolus injection of four various GSH doses (50 to 300 mumol kg-1), arterial plasma concentrations of GSH, GSSG (= oxidized glutathione), total thiols and soluble thiols minus GSH were elevated and then rapidly decreased nonexponentially. With increasing dose, the rate constant for drug elimination and plasma clearance increased from 0.84 to 2.44 ml min-1 and the half-life of the elimination phase decreased from 52.4 to 11.4 min. Both the apparent volume of distribution and the degree of penetration of GSH into the tissues were diminished with increasing dose (from 3.78 to 1.33 litres kg-1 and from 6.00 to 0.51 as k12/k21, respectively). The data indicate that GSH is rapidly eliminated. This is mainly due to rapid oxidation in plasma rather than by increased tissue extraction or volume distribution. Thus plasma GSH levels appear to be quickly regulated by which the body may maintain concentrations within narrow physiological limits. PMID- 2878991 TI - An approach to reduce the number of skin samples in testing the transdermal permeation of drugs. AB - Although glyceryl trinitrate (GT) is a drug that easily permeates through skin, the variations in its transepidermal fluxes were high. The arithmetic mean of the GT flux (n = 31 skin samples from different individuals) was 16.5 micrograms cm-2 h-1 with a standard deviation of 42%. The extreme values were 4.1 and 36.9 micrograms cm-2 h-1, i.e. they differed by a factor of 9. Wide variations were also found for ephedrine, frusemide, caffeine, ethacrynic and benzoic acids and especially trospium chloride. All these fluxes were determined in an in-vitro permeation model at 32 degrees C using human epidermis. With the aim of standardizing epidermal preparations on their permeability, the extent to which the in-vitro GT fluxes through a human epidermal preparation correlate with those of other compounds was evaluated. The resulting standardization procedure consisted of two interactive parts: the correlation of the flux of a test substance with that of GT using epidermal samples from three donors and estimating the minimum, mean and maximum flux of the test compound and quantitation of the transepidermal permeation of the test compound with those standardized epidermal preparations by calculating the GT standard coefficient defined by the slope of the line derived from the relation between GT flux units and the corresponding flux from the test compound. PMID- 2878992 TI - Antihistamine-sensitive active vasodilatation in the perfused hindquarters of the rat. AB - The innervated, constant flow perfused hindquarters of the rat have been used to evaluate post-stimulation vasodilatation, which is a model of active reflex vasodilatation in this species. The vasodilatation resulting from lumbar sympathetic stimulation was dependent on stimulation frequency and duration. Maximal vasodilatation (16 +/- 2%) was at 8 Hz for 15 s, while markedly reduced vasodilatation was seen after stimulation for longer than 30 s at all frequencies tested. The vasodilatation was transient. Atropine (2.0 mg kg-1 i.v.) failed to attenuate post-stimulation vasodilatation at a time when hindquarter vasodilatation to i.a. acetylcholine had been abolished. The H1 antihistamine, tripelennamine (2.5 mg kg-1 i.v.) significantly reduced (77%) post-stimulation vasodilatation relative to controls at a time when hindquarter vasodilatation due to i.a. histamine was essentially abolished. Reactive hyperaemia is an unlikely cause of vasodilatation since it is not blocked by H1 antihistamines; 60 s post occlusion hyperaemia also, was not demonstrable. These data suggest that there is an active component of baroreceptor-mediated vasodilatation in the rat and that histamine, rather than acetylcholine, could be a mediator of this vasodilatation. PMID- 2878994 TI - Inhibitory effects of sympathomimetic drugs on cholinergically mediated contractions of guinea-pig isolated tracheal muscle. AB - The experiments examine the actions of sympathomimetic drugs on the responses evoked by electrical field stimulation or by acetylcholine in guinea-pig tracheal strip chains. Electrical field stimulation evoked contractions which were cholinergically mediated, in the presence of guanethidine (10 microM) and indomethacin (2 microM). All the sympathomimetic drugs tested caused a concentration-dependent reduction in the height of these contractions. Inhibitory effects of isoprenaline and terbutaline were largely prevented by propranolol (2 microM) alone, whereas those of clonidine, oxymetazoline, lidamidine and WHR1370 were prevented by yohimbine alone (2 microM). Treatments with both propranolol and yohimbine were required to prevent the inhibitory effects of noradrenaline, adrenaline and dopamine. Contractions evoked by exogenous acetylcholine (0.1-3 microM) were also inhibited by all catecholamines and terbutaline, but not by clonidine, oxymetazoline, lidamidine and WHR1370. The inhibitory effects were antagonized by propranolol (2 microM) alone. The results suggest that in guinea pig isolated tracheal muscle, sympathomimetic drugs can inhibit cholinergic neurotransmission not only by postjunctional beta 2-adrenoceptors but also by prejunctional alpha 2-adrenoceptors. PMID- 2878993 TI - Ketanserin potentiates the prejunctional inhibitory effect of 5-hydroxytryptamine on rat vas deferens. AB - 5-Hydroxytryptamine (5-HT) slightly inhibited the twitch contractions of rat vas deferens caused by single pulse field stimulation at 0.1 Hz. The inhibitory effect of 5-HT was much less in the epididymal portion than in the prostatic portion of the vas deferens. Ketanserin potentiated the prejunctional inhibitory effect of 5-HT and attenuated its stimulatory effect. This potentiation was observable only in the epididymal portion, of the vas deferens. Cyproheptadine and mianserin, but not methysergide, had essentially similar potentiating effects to those of ketanserin. These results suggest that the 5-HT receptor that mediates prejunctional inhibition is not of the 5-HT2 type, and that ketanserin acts by suppressing the 5-HT-induced stimulatory effect, which is possibly mediated by a postjunctional 5-HT2 receptor, thus unmasking the inhibitory effect of 5-HT. PMID- 2878995 TI - Analgesic and anti-inflammatory activities in rats of alpha-(3,5-di-t-butyl-4 hydroxybenzylidene)-gamma-butyrolactone (KME-4), and its intestinal damage. AB - alpha-(3,5-Di-t-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), an anti inflammatory drug, possesses analgesic activity in rat models. In the acetic acid induced writhing test, the oral ED50 values for KME-4, indomethacin, naproxen and ibuprofen were 5.2, 3.8, 7.0 and 18.6 mg kg-1, respectively, and the relative order of potency of these drugs correlated with their inhibitory effect on acetic acid-induced vascular permeability in rats. KME-4 also had analgesic activity in the tests of Randall-Selitto and adjuvant arthritic flexion, but the dose required was greater than that needed in the writhing test. KME-4 (10 mg kg-1 day 1 orally) has a preventive effect against adjuvant-induced arthritis in rats, and its efficacy was more potent than indomethacin (2 mg kg-1 day-1) as judged from various parameters determined. When administered orally to rats once daily for 12 days, KME-4 caused perforating ulceration of the small intestine but this action was less potent than the effect of indomethacin, naproxen and ibuprofen. PMID- 2878996 TI - Pharmacological actions of ICI 180080, a novel thromboxane receptor antagonist. AB - ICI 180080 (5(Z)-7-[2,2-dimethyl-4-(2-hydroxyphenyl)-1,3-dioxan-cis-5-yl] heptenoic acid) potently inhibited contractions of rat and rabbit aortae and guinea-pig trachea elicited by 11,9-epoxymethano PGH2 (U-46619). This antagonism was selective because contractions of aortae to noradrenaline and 5 hydroxytryptamine and trachea to histamine were not antagonized by ICI 180080. Schild analysis of data obtained from experiments on rabbit aortae indicated that this thromboxane receptor antagonism was competitive (pA2 = 7.50, slope = 1.07). Addition of ICI 180080 to human platelet-rich plasma caused dose-related inhibition of U-46619-induced platelet aggregation. This modification of platelet aggregation was not associated with inhibition of thromboxane synthetase, cyclo oxygenase or lipoxygenase. ICI 180080 did not modify the primary phase of ADP induced aggregation of human platelets neither did it affect the platelet inhibitory activity of prostacyclin. When dosed orally to anaesthetized guinea pigs, ICI 180080 (5-50 mg kg-1) caused dose-related inhibition of U-46619-evoked bronchoconstriction. We conclude that ICI 180080 is a potent, selective, competitive, orally active thromboxane antagonist. PMID- 2878997 TI - The degradation of temocillin, a 6 alpha-methoxypenicillin, and identification of the major degradation products. AB - Temocillin, 6 beta-(R,S-2'-carboxy-2'-thien-3-ylacetamido)-6 alpha methoxypenicillanic acid, shows good stability in mild aqueous acid or base; in stronger acid the methoxypenillic acid is formed whereas alkaline or enzyme hydrolysis results in the formation of the methoxypenicilloic acid and the C-5 epimer. PMID- 2878998 TI - The pH-dependence of chloroquine uptake by phosphatidylcholine vesicles. AB - The pH-dependence of chloroquine uptake by phosphatidylcholine bilayered vesicles was investigated to examine the relative affinity of ionized and un-ionized chloroquine species to membrane bilayers. The results suggest that the neutral species and monocation are taken up by the bilayers but only the un-ionized species interacts significantly with the hydrocarbon interior. PMID- 2878999 TI - Direct measurements on individual microcapsule dissolution as a tool for determination of release mechanism. AB - A method is described for simultaneous microscopic observation of individual microcapsule core material dissolution together with quantitative measurement of the individual kinetics of release of the contents. These may be conductimetric in the case of ionized materials or spectrophotometric otherwise. This enables correlation of changes in core surface area during dissolution with kinetics. Surprisingly, both ethyl cellulose- and polymethacrylate-coated cores of potassium dichromate crystals, used as a model, showed localized internal dissolution universally, providing evidence of the exit of the salt via pores in the membrane, in spite of the kinetics being invariably zero order, as expected for individual microcapsules. The advantages of the method are presented. PMID- 2879000 TI - Evidence against VIP-involvement in neurogenic relaxations of the mouse anococcygeus muscle. AB - Vasoactive intestinal polypeptide (VIP) antiserum, alpha-chymotrypsin, and repeated exposure to VIP markedly reduced relaxations of the mouse anococcygeus muscle to VIP but not to field stimulation. This evidence suggests that VIP does not mediate non-adrenergic, non-cholinergic relaxations in the mouse anococcygeus. PMID- 2879001 TI - The effect of digoxin-specific active immunization on digoxin toxicity and distribution in the guinea-pig. AB - In guinea-pigs intravenously infused with digoxin, prior immunization using a digoxin-human serum albumin conjugate increased by 3- and 2.4-fold, respectively, the digoxin doses causing the first signs of cardiotoxicity and death. At death, serum digoxin concentration was four times higher in immunized than in control animals. In the immunized guinea-pigs 50% of the serum digoxin was protein bound, presumably mainly to digoxin-specific antibodies, since in the controls the bound fraction was only 1-2%. Generally, tissue digoxin concentrations were not increased to the same extent as the lethal dose, and in the heart and lungs the increase was not significant. With cardiac (ventricle) subcellular fractions, there was no difference between control and immunized animals in the digoxin concentration of the 'microsomal' pellet. This subfraction contains the plasma membrane and the associated sodium pumps which are considered to be the sites at which the pharmacologically active digoxin binds. It seems likely, therefore, that the greater digoxin resistance in the immunized animals can be explained on the basis of reduced drug access to the site of action within the heart. PMID- 2879002 TI - Antiarrhythmic effect of acute and chronic amiodarone treatment in conscious rats. AB - The effect of amiodarone after acute and chronic pretreatment was studied in the early phase of arrhythmias induced by coronary artery ligation in conscious rats. Both acute and chronic amiodarone pretreatments improved survival during the first 20 min after coronary ligation. Only chronic amiodarone pretreatment reduced significantly the incidence of ventricular fibrillation. It was concluded that chronic amiodarone pretreatment seemed to be more effective than the acute one. PMID- 2879003 TI - Adrenal catecholamine concentration after chronic treatment with bromocriptine and haloperidol. AB - Adrenal catecholamine concentration was measured by HPLC with electrochemical detection in male rats after ten days of bromocriptine and haloperidol (0.05, 0.5 and 5.0 mg kg-1) and vehicle (1.0 ml kg-1) treatments subcutaneously. There were four rats in each group. The results indicate that bromocriptine treatment significantly increased dopamine (DA), noradrenaline (NA) and adrenaline (A) content in a dose-dependent manner. The NA/DA ratio was unchanged, but the A/NA ratio was significantly increased after treatments with two higher doses of the drug. Haloperidol treatment, on the other hand, had no significant effect on dopamine and a biphasic effect on adrenaline content. Noradrenaline concentration increased only after the lowest dose of the drug. There was no significant change in NA/DA or A/NA ratios in any group. The dopamine metabolite, dihydroxyphenylacetic acid (DOPAC), was not detected in any adrenal gland. PMID- 2879004 TI - Effects of sulphonylureas on spontaneous motility and induced contractions in rat isolated uterus. AB - To clarify the action of sulphonylureas on calcium, the effect of tolbutamide and glibenclamide has been investigated on a Ca-dependent process, the contractile activity of uterine smooth muscle. Both sulphonylureas antagonized the contractions evoked by CaCl2 in a non-competitive manner when the uterus was maintained in depolarizing solution and did not affect the spontaneous contractions of rat uterus. The capacity of tolbutamide and glibenclamide to relax vanadate-induced contraction of rat uterus in Ca-free medium suggests that sulphonylureas may have an intracellular site of action related to cytosolic free Ca levels, or effect a reduction in Ca action. PMID- 2879005 TI - The metabolism of atropine in man. AB - A metabolic pattern of atropine in man, based on the detection of radiolabelled products in urine by high performance liquid chromatography after administration of [3H]atropine sulphate to a normal volunteer is proposed. Noratropine (24%), atropine-N-oxide (equatorial isomer) (15%), tropine (2%) and tropic acid (3%) appear to be the major metabolites, while 50% of the administered dose is excreted as apparently unchanged atropine. No conjugates were detectable. Evidence that atropine is present as (+)-hyoscyamine was found, suggesting that stereoselective metabolism of atropine probably occurs. PMID- 2879006 TI - Evaluation of official instrumental methods for the determination of particulate matter contamination in large volume parenteral solutions. AB - The distribution pattern of particle contamination in nine different types of LV parenteral solutions and the possibility of correlating the counts made with two official instruments (Coulter Counter and HIAC) were studied. Two hundred containers of LV parenteral solutions (corresponding to 40 batches) produced in Italy, were sampled. Each bottle was submitted to HIAC and Coulter Counter countings, for particle sizes ranging between 2 and 25 micron. For about 50% of the products, the two straight lines that represent the distribution of particle contamination obtained with the two methods did not cross-over within the studied size range, the Coulter Counter counts always proving higher than the HIAC ones. In the other cases, the cross-over point of the two lines occurred at varying size levels. Statistical analysis of the results pointed to a relationship between the contamination values obtained with the two counting methods for sizes ranging between 2 and 5 micron, but there was no correlation for sizes equal to, or higher than, 10 micron. From the maximum contamination levels established by the BP and the FU IX for the HIAC method, the corresponding values were calculated for the Coulter Counter method. Similarly the values were calculated the HIAC method based on the maximum values set for the Coulter Counter. PMID- 2879007 TI - The components of Melissa officinalis L. that influence protein biosynthesis in vitro. AB - An investigation of an inhibiting activity of a substance(s) in a tanninless extract from Melissa officinalis leaves on protein biosynthesis in-vitro has been made. At least two components which inhibited protein biosynthesis were present in the extract; these were caffeic acid and an unidentified glycoside. Freshly prepared buffered solutions of caffeic acid inhibited protein biosynthesis less than solutions stored for several days at room temperature (20 degrees C). In this case derivatives of caffeic acid were formed, which may be responsible for the increase in the inhibitory effect of stored caffeic acid solution. An inhibitor, in the homogeneous state, was also isolated from the glycoside fraction of M. officinalis. Studies on the mechanism of the action of this inhibitor revealed its effect is to use the result of a direct interaction with elongation factor EF-2, and the blocking of the binding reaction of EF-2 with ribosomes. PMID- 2879008 TI - Non-isotopic spectrophotometric determination of the unbound fraction of drugs in serum. AB - A spectrophotometric method to measure the free fraction of highly-bound drugs in serum has been established for a range of non-steroidal anti-inflammatory drugs (NSAIDs) and for frusemide. Spectrophotometry is used to measure fractional transit of drug from a large volume of dialysate to a small volume of serum during dialysis to equilibrium. The method, which depends on the principle that drug transit from dialysate to serum is proportional to serum binding, requires neither isotopic drug preparations nor specific drug assays, is independent of extraction efficiency from the dialysate and requires no measurements from the serum compartment. Estimates of percent unbound fraction (% UF) for aspirin (6.0 +/- 0.9%), phenylbutazone (0.9 +/- 0.2%), and frusemide (1.8 +/- 0.2%) were comparable with those obtained with 14C drug preparations. Values for % UF were determined for eleven additional NSAIDs. The method was valid for a four-fold change in serum: dialysate ratio. Kinetics of frusemide binding to serum were comparable using [14C]frusemide and the test method. This technique may have general application in establishing the % UF for substances that are extensively bound to serum proteins and for identifying sera that show abnormal binding. PMID- 2879009 TI - Effect of particle size and food on gastric residence time of non-disintegrating solids in beagle dogs. AB - The gastric residence times of various sizes of radio-opaque particles and tablets were measured in beagle dogs by X-ray, both in the fasted state and after a single meal. During the course of the studies, changes in intragastric pH were also monitored with a radiotelemetric pH sensor, the Heidelberg capsule. The gastric residence time increased with increasing particle size and with particles greater than or equal to 5 mm in diameter approached a plateau value both in the fasted state and after feeding. This value was about 7.5 h after feeding and about 1.5 h in the fasted state, and probably corresponded to the occurrence of the interdigestive migratory myoelectric complex (IMMC wave). The pH in the stomach was variable in the fasted state, but an abrupt pH increase (up to pH 6 7) was observed during the emptying of larger tablets. In some instances this high pH in the stomach was maintained until the next IMMC wave occurred. The gastric emptying of larger tablets administered with food was also associated with an abrupt pH increase. PMID- 2879010 TI - Modification of electrical field stimulation-induced contractions in the guinea pig ileum by metoclopramide and ICS 205-930 depends on the integrity of the mucosa. AB - Contractions induced by electrical field stimulation of guinea-pig ileum longitudinal muscle strips were enhanced by metoclopramide and ICS 205-930 at concentrations similar to those required to antagonize at 5-hydroxytryptamine 'M' receptors. The enhancement of contraction was observed in intact ileum strips but was not recorded in the longitudinal muscle myenteric plexus preparation or from the ileum with the mucosal layer removed. It is concluded that an intact mucosal layer is required for metoclopramide and ICS 205-930 to enhance electrical field stimulation-induced contractions of the guinea-pig ileum. PMID- 2879011 TI - The effect of pH and concentration on alpha-methyldopa absorption in man. AB - An open crossover study of the absorption of alpha-methyldopa has been conducted in normal healthy adult male volunteers in whom a triple lumen perfusion tube had been placed. Three volunteers were perfused on separate occasions with 0.1 mM alpha-methyldopa at pH 4.5, 6.0 and 7.4. Three other volunteers were perfused on separate occasions with 0.1, 1.0 and 10 mM alpha-methyldopa at pH 6.0. Two additional subjects were perfused with 0.1 mM alpha-methyldopa at pH 6.0. Absorption was not a linear function of concentration above 1 mM alpha methyldopa. There was also a weak trend toward greater absorption near pH 6.0. At higher concentrations of drug in the perfusion solution (10 vs 1 mM), the free fraction of alpha-methyldopa in plasma samples was increased significantly. Thus, although absorption of alpha-methyldopa is more efficient at lower concentrations, bioavailability may not be substantially enhanced due to increased sulphation in the gut wall. Comparison of permeabilities with previous results from our laboratories suggests the rat is a good model for predicting the behaviour of alpha-methyldopa after its oral administration to man. PMID- 2879012 TI - Effects of various cephem antibiotics on ethanol metabolism and their structure activity relations. AB - The effects of various cephem antibiotics and related compounds on ethanol metabolism were studied in association with their chemical structures. In rats, cefoperazone, cefbuperazone, cefamandole, latamoxef, cefmetazole, cefotetan, cefmenoxime and cefminox which have the [(1-methyl-1H-tetrazol-5-yl) thio] methyl group at position 3 of the cephem ring caused a significant increase in the blood acetaldehyde concentration. In the last three compounds, disulfiram-like activity was less potent than that evaluated in the preceding compounds. Cefazolin and ceftezole having a 1H-tetrazol group at position 7 also showed a disulfiram-like activity. A single administration of 1H-tetrazol also increased the blood acetaldehyde concentration. Both blood ethanol and acetaldehyde values were increased significantly on administration of these drugs. In beagle dogs, cefoperazone induced a less remarkable but much more sustained increase in the blood acetaldehyde. These results indicate that the 1H-tetrazol group, as well as the [(1-methyl-1H-tetrazol-5-yl) thio] methyl group, is responsible for inducing a disulfiram-like action and that there is a difference in the potency of the disulfiram-like activity among the drugs having a [(1-methyl-1H-tetrazol-5 yl)thio] methyl group at position 3 of the cephem ring in relation to those in which the side chain is substituted at position 7. PMID- 2879013 TI - Effects of antimalarial drugs on interleukin 1-induced cartilage proteoglycan degradation in-vitro. AB - Previous studies having shown that chloroquine and hydroxychloroquine could reduce interleukin 1 (IL-1)-induced cartilage degradation in-vitro, the effects of a range of antimalarial drugs on the cartilage proteoglycan degrading actions of porcine leucocyte (pI 4.8) alpha-interleukin 1 (syn. catabolin) have been examined using the standard bovine nasal cartilage culture system. The anti-IL-1 effects in this system were specific to several aminoquinoline and aminoacridine analogues having a side chain with a tertiary amino group similar to that of chloroquine. Aminoquinoline compounds devoid of this side chain and the tertiary amino, as well as pyrimidines or biguanides with antimalarial activity were without effect. Mefloquine, the most potent of the compounds active against porcine alpha-IL-1, was only equipotent with chloroquine and its hydroxyanalogue against human recombinant alpha-IL-1. This suggests that there may be subtle differences in the receptors for these drugs and interleukins in bovine cartilage. The results provide further evidence for the specificity and utility of antimalarial drugs in the treatment of chronic inflammatory conditions, especially in relation to actions on IL-1. PMID- 2879014 TI - Rapid drug haptenization procedure: application to gentamicin and quinidine. AB - A rapid and simple drug conjugation procedure which utilizes the heterobifunctional reagent N-hydroxysuccinimidyl 6-(4'-azido-2' nitrophenylamino)hexanoate is described. With this protocol two drugs of diverse structure and solubility have been successfully haptenized. Rabbits immunized with these conjugates yielded drug-specific antibodies as judged by a solid phase radioimmunoassay. Furthermore, using this technique, no cross-reactivity could be detected. Such haptens also elicited an immune response in mice thus further extending their potential for the production of drug specific monoclonal antibodies. PMID- 2879015 TI - The effect of food on the bioavailability and kinetics of the anticancer drug amsacrine and a new analogue, N-5-dimethyl-9-[(2-methoxy-4 methylsulphonylamino)phenylamino]-4 acridinecarboxamide in rabbits. AB - Both amsacrine and its analogue, N-5-dimethyl-9-[(2-methoxy-4- methylsulphonylamino)phenylamino]-4-acridinecarboxamide (CI-921) are absorbed from the gastrointestinal tract in rabbits. The mean bioavailability for amsacrine was 50% +/- 17 (s.d.) in non-fasting animals, and was significantly increased in fasting animals (mean, 90% +/- 10). The bioavailability for CI-921 (mean, 26% +/- 11) in the non-fasting animal was significantly less than that found for amsacrine, but this difference disappeared in the fasting animal when the bioavailability of CI-921 was significantly increased to 69% +/- 23. Oral administration of both agents resulted in significantly prolonged elimination half-lives and mean residence times compared to the i.v. infusion, but no significant difference was observed in these parameters between the fasting and non-fasting state. This study suggests that oral dosing may be a possible alternative route for the administration of these anticancer agents. PMID- 2879017 TI - The affinity of some selective muscarinic receptor antagonists for the muscarinic receptor mediating endothelial-dependent relaxation of the rabbit and rat thoracic aorta. AB - The pKB values determined for pirenzepine, 4-DAMP, secoverine and gallamine against acetylcholine-mediated relaxant effects in rabbit aorta indicate that this muscarinic receptor closely resembles that which mediates contraction of non vascular smooth muscle. The results of the present study argue against the presence of a novel type of muscarinic receptor mediating endothelium-dependent relaxation. PMID- 2879016 TI - The pharmacokinetics of pyrimethamine in the rat: effect of mefloquine. AB - The pharmacokinetics and tissue distribution of pyrimethamine have been determined in the rat. Following administration of pyrimethamine alone, drug concentrations declined biexponentially. By contrast, in the presence of mefloquine, the decline in pyrimethamine concentration more closely fitted a monoexponential pattern and the AUC0-6h for pyrimethamine was significantly reduced. Significantly more pyrimethamine was recovered from the livers but less from the lungs of the mefloquine-dosed rats compared with control. This study outlines a potentially clinically relevant drug interaction. PMID- 2879018 TI - Luminal acid in stress ulceration and the antiulcer action of verapamil in rat stomachs. AB - The role of luminal acid and the influence of the antisecretory action of verapamil in stress ulcer prevention in rat stomachs have been studied. Intraperitoneally injected verapamil, 4 mg kg-1, inhibited gastric acid secretion and ulcer formation, however, a 2 mg kg-1 dose, which did not significantly influence acid output, also had an antiulcer effect. Intraperitoneal injection of bethanechol, 1.2 or 3.6 mg kg-1, increased gastric acid output, but did not influence stress-induced ulcer formation. Oral administration of HCl, 25 or 50 mu equiv, aggravated stress ulceration in a dose-dependent manner; this lesion worsening effect was prevented by pretreatment with verapamil or bethanechol. The gastric luminal acid content in 2 h pylorus-ligated rats was similar in the groups given either bethanechol or HCl. These findings indicate that the antisecretory action of verapamil may not account for its antiulcer effect. It is suggested that endogenous and exogenous luminal acid may have different influences on stress ulcer formation. PMID- 2879019 TI - Tissue cholinesterase inhibition by propranolol and related drugs. AB - The effect of (+/-)-propranolol and some related drugs have been investigated on the cholinesterase (ChE) enzyme activity of heart and brain tissues of the rat. Brain homogenates hydrolysed more methacholine than benzoylcholine and the reverse was true for the heart tissue. In-vitro, (+/-)-, (+)- and (-) propranolol, as well as its quaternary analogue, UM-272, all significantly inhibited heart and brain ChE. Timolol and sotalol, however, were less potent. In vivo, (+/-)-propranolol (30 mumol kg-1) significantly inhibited brain ChE activity in rats when compared with saline controls. It is inferred that propranolol inhibits brain and heart ChE enzyme in a non-stereoselective manner and that this cholinomimetic action could be involved in the mediation of some of its therapeutic effects. PMID- 2879020 TI - The adenosine receptor antagonist, 8-phenyltheophylline, causes diuresis and saliuresis in the rat. AB - The diuretic and adenosine antagonist actions of two alkylxanthines have been compared in the conscious rat. 8-Phenyltheophylline (10 mg kg-1) antagonized adenosine-induced bradycardia in the rat for at least 3 h whereas enprofylline (10 mg kg-1) had no effect on this response. 8-Phenyltheophylline (10 mg kg-1) evoked diuresis and saliuresis in the rat whereas enprofylline (10 mg kg-1) had no effect on excretory parameters. These results indicate that the diuretic action of some alkylxanthines may be related to adenosine antagonism. PMID- 2879022 TI - Effect of adrenergic drugs on the isolated colon of Rhesus cynomolgus. AB - The effects of adrenaline, noradrenaline, isoprenaline and dopamine were studied on the longitudinal muscle of the ascending and descending colon of the rhesus monkey. All these drugs induced a relaxation of the preparation, dopamine being the less active agonist. The responses seem to be the result of beta 2 adrenoceptor stimulation since their inhibition by practolol (beta 1) is weaker than their inhibition by propranolol (beta 1 and beta 2 dopaminergic). There is no evidence for the presence of dopaminergic receptors in this preparation. PMID- 2879021 TI - Inhibition of dimaprit- and pentagastrin-induced gastric acid secretion in cats by the new histamine H2 antagonist, CM 57755. AB - The antisecretory effects of CM 57755, a new histamine-H2 receptor antagonist, have been compared with those of cimetidine on gastric acid secretion induced by intravenous infusions of dimaprit or pentagastrin into conscious cats with chronically implanted gastric fistulae. Intravenous infusion of CM 57755 induced a parallel shift to the right of the dimaprit dose-response curve. The potency of CM 57755 was comparable with that of cimetidine as shown by similar doses causing a 5-fold displacement to the right of the dimaprit dose-response curve (4.9 mumol kg-1 h-1 for CM 57755 and 4.7 mumol kg-1 h-1 for cimetidine). Unlike that with dimaprit, the acid secretion stimulated by increasing doses of pentagastrin was inhibited by CM 57755 with depression of the maximal effect, indicating non competitive antagonism. In a second series of experiments the time course of the anti-secretory action of intragastrically administered CM 57755 was studied from the gastric acid secretion induced by constant infusion of dimaprit. At equieffective doses, CM 57755 caused more sustained inhibition than cimetidine. PMID- 2879023 TI - Amethocaine-induced inhibition of mitochondrial monoamine oxidase activity. AB - Amethocaine (tetracaine) (1-10 microM) produces a concentration-dependent in vitro inhibition of mitochondrial membrane-bound MAO activity towards tyramine (18-84% in brain and 19-84% in liver) and 5-hydroxytryptamine (5-HT) (23-94% in brain and 20-100% in liver). At relatively higher concentrations (25-300 microM) of amethocaine, benzylamine oxidation is inhibited in brain (24-91%) and liver (29-100%). The extent of MAO inhibition is appreciably reduced when preincubation time of the enzyme with a low concentration (7.5 microM) of amethocaine is increased from zero to 45 min. This inhibition is reversible. The Km of MAO for tyramine is increased in brain (106-473%) and liver (121-352%) in the presence of amethocaine (2-7.5 microM) accompanied by a decrease in Vmax (21-51% in brain and 18-57% in liver). Similarly the Km of MAO for 5-HT is increased to the extent of 79-336% in brain and 51-225% in liver and the corresponding Vmax is decreased by 35-55% and 39-74%, respectively, in the presence of 2-5 microM amethocaine. At relatively higher concentrations (25-100 microM), amethocaine increases the Km of MAO for benzylamine in brain (25-101%) and liver (26-85%) and decreases the Vmax by 28-64% and 32-63% in the respective tissues. Thus these results suggest that amethocaine preferentially inhibits MAO-A and the nature of inhibition is reversible and of mixed type. PMID- 2879024 TI - Antiarrhythmic effect of amperozide, a novel psychotropic compound with class III antiarrhythmic properties, on digoxin-induced arrhythmias in the guinea-pig. AB - Amperozide is a novel psychotropic compound with specific effect in limbic brain areas. Preliminary findings have also indicated an antiarrhythmic effect in vitro. Injections of saline, amperozide, melperone, thioridazine, bretylium or lignocaine, were given i.p. to anaesthetized guinea-pigs, which 10 min later were given digoxin s.c. to induce arrhythmia. In a series of control experiments none of these compounds caused arrhythmia in combination with the vehicle of digoxin. The time to arrhythmia was significantly prolonged after treatment with amperozide, melperone and bretylium compared with saline, but there were no differences between the treatments. The digoxin concentrations in plasma at death varied considerably within the groups and no statistical significance was found. PMID- 2879025 TI - Bioavailability of sustained release acetazolamide. PMID- 2879026 TI - British pharmaceutical conference 1986. Science proceedings. 123rd meeting, Jersey, September 22-25, 1986. Abstracts. PMID- 2879027 TI - Bovine anterior descending coronary artery possesses a homogeneous population of beta-1 adrenergic receptors. AB - Isolated vessel rings from the proximal and distal ends of the bovine anterior descending coronary artery were mounted in tissue baths for the measurement of isometric contraction. These rings were pre-exposed to phenoxybenzamine to block tissue catecholamine uptake and alpha adrenoceptors. They were then contracted with high potassium, and beta adrenergic agonist dose-relaxation response curves were obtained in the presence and absence of beta antagonists. The orders of agonist potency in the arterial rings were the same as that in spontaneously beating guinea pig atria: isoproterenol (ISO) greater than norepinephrine (NE) greater than fenoterol (FE) greater than salbutamol (SA) and differed from that in the guinea pig trachea: ISO greater than FE greater than SA greater than NE. Schild analysis yielded propranolol pA2 values in the coronary artery rings which did not differ between the four agonists studied or between the proximal and distal ends of the coronary artery. Similar results were obtained with practolol and butoxamine with the exception that in the case of butoxamine, a higher pA2 value was obtained against ISO in the distal ring preparations. The practolol and butoxamine pA2 values in the artery rings matched the respective--log KB values obtained in the guinea pig atria using NE as the agonist but were the reverse of those obtained in the guinea pig trachea using either FE or SA as the agonist. It is concluded that the proximal and distal ends of the bovine anterior descending coronary artery possess a homogeneous population of beta-1 adrenergic receptors. PMID- 2879028 TI - Alpha adrenoceptor regulation of coronary artery blood flow in normal and stenotic canine coronary arteries. AB - The response of systemic blood pressure, heart rate, lead II ECG and left circumflex (LCX) coronary artery blood flow to left cardiac sympathetic nerve stimulation was measured in pentobarbital-anesthetized, open chest, spinal transected and vagotomized dogs. After beta adrenoceptor blockade, left cardiac sympathetic nerve stimulation produced frequency dependent decreases in LCX blood flow. Selective alpha-2 adrenoceptor blockade with idazoxan produced a greater inhibition of this decrease in LCX blood flow than did selective alpha-1 adrenoceptor blockade with prazosin. In an additional population of dogs which were similarly prepared but were not spinally transectioned or pretreated with a beta adrenoceptor antagonist, left cardiac sympathetic nerve stimulation produced an increase in LCX blood flow in all animals which reached a maximum within 40 sec, and then began to decline slowly. However, after beta adrenoceptor blockade, identical stimulation parameters produced only a decline in LCX blood flow which returned to the level of control resting blood flow by the end of the stimulation period. Both selective alpha-2 adrenoceptor blockade with idazoxan and selective alpha-1 adrenoceptor blockade with prazosin produced an inhibition of the LCX blood flow decrease provoked by left cardiac sympathetic nerve stimulation in dogs pretreated with beta adrenoceptor antagonists. Idazoxan produced a slightly greater inhibition of the LCX blood flow decrease than did prazosin, suggesting a greater role for postjunctional vascular alpha-2 adrenoceptors in LCX blood flow regulation during cardiac sympathetic nerve stimulation. The presence of a severe coronary artery stenosis reduced, but did not inhibit, the increase in LCX blood flow in response to cardiac sympathetic nerve stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879029 TI - Down regulation of beta adrenergic receptors in S49 lymphoma cells induced by atypical agonists. AB - The ability of the atypical agonists celiprolol and pindolol to induce sequestration and down regulation of beta adrenergic receptors was investigated in S49 lymphoma cells. Sequestration was measured as the loss of binding sites for [3H]CGP-12177, a hydrophilic radioligand that binds only to surface beta adrenergic receptors at 6 degrees C. Down regulation was measured as the loss of binding sites for [125I]iodopindolol, a lipophilic radioligand which at 37 degrees C binds to both surface and sequestered receptors. Pindolol and celiprolol do not stimulate adenylate cyclase in membranes from wild-type (WT) S49 cells or do they induce the sequestration of beta adrenergic receptors on intact cells. Incubation of WT S49 lymphoma cells with isoproterenol for 24 hr resulted in the loss of 75% of total cellular beta adrenergic receptors (down regulation). Exposure of WT S49 cells to pindolol or celiprolol for 24 hr resulted in the loss of approximately half of the total cellular beta adrenergic receptors. In mutant S49 cells [cyc- (variant of S49 lymphoma cells which lacks Ns activity) and UNC (variant of S49 lymphoma cells in which Ns is present but cannot interact with beta adrenergic receptors)] in which interaction of beta adrenergic receptors with the stimulatory guanine nucleotide binding regulatory protein (Ns) does not occur, a 24 hr incubation with isoproterenol caused the loss of approximately half of the beta adrenergic receptors, whereas pindolol and celiprolol caused no change in the number of receptors. These results suggest that there are two mechanisms of down regulation of beta adrenergic receptors in S49 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879030 TI - Modulation of the carrier-mediated transport of the Tyr-MIF-1 across the blood brain barrier by essential amino acids. AB - There is evidence that the carrier-mediated system capable of transporting small, N-tyrosinated peptides [e.g., Tyr-Pro-Leu-Gly-NH2 (N-Tyr-MIF-1) and enkephalins] across the blood-brain barrier is modulated by intraventricularly administered leucine. This raises the possibility that the toxicity of amino acids on the central nervous system may be mediated in part by alterations in blood-brain barrier function. We further examined this action of leucine and extended the investigation to include other essential amino acids. High doses of leucine (30 nM and 100 nM/mouse intraventricularly) were found to inhibit significantly transport of iodinated Tyr-MIF-1 out of the brain. Less consistently, a low dose of leucine (1.0 nM/mouse) stimulated transport. Kinetic analysis indicated that leucine produced an uncompetitive type of modulation, probably interacting with the carrier-ligand complex. Among the other amino acids studied, D-leucine inhibited transport at both 1 nM and 100 nM/mouse, but stimulated transport at 0.1 nM/mouse. The only other significant changes occurred at the high (100 nM) dose of arginine, which stimulated, and methionine, which inhibited, transport. The possibility is proposed that derangements in amino acid metabolism might produce some of their effects on the central nervous system by modulating the blood-brain barrier transport systems for peptides and possibly other substances. PMID- 2879031 TI - Alpha-1 adrenergic receptor binding and contraction of rat caudal artery. AB - Alpha-1 adrenergic receptors were examined in rat caudal artery using radioligand binding of [125I]labeled BE 2254 (125IBE) and in vitro contraction measurements. 125IBE bound rapidly and reversibly to a single class of high affinity binding sites in membrane preparations of caudal artery. Scatchard analysis gave an equilibrium dissociation constant (KD) of 110 pM and a density of binding sites of 115 fmol/mg of protein. Antagonists inhibited 125IBE binding and phenylephrine induced contractions competitively, with an order of potency of prazosin greater than ARC 239 greater than phentolamine greater than yohimbine. pA2 values for inhibition of phenylephrine-induced contraction correlated well with KD values for inhibition of specific 125IBE binding. A number of other full and partial agonists also caused contraction of caudal arteries with an order of potency of epinephrine greater than norepinephrine greater than phenylephrine greater than methoxamine. The order of potency of agonists and the potencies of antagonists suggests that the contractile responses of rat caudal artery were mediated by alpha-1 adrenergic receptors. The EC50 values of partial agonists in causing contraction correlated well with their KD values for inhibition of specific 125IBE binding. However, the EC50 values for full agonists were 30 to 200 times lower than their KD values. Treatment of caudal arteries in vitro with 0.1 microM phenoxybenzamine for 10 min to inactivate alpha adrenergic receptors decreased both the potency of full agonists in causing contraction and the maximal contractile response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879033 TI - Endothelial potentiation of relaxation response to beta adrenoceptor blocking agents. AB - A number of beta adrenergic blocking drugs were evaluated on ring preparations of endothelium intact and denuded segments of the rat aorta. The preparations were preconstricted under isometric conditions with an EC80 dose of phenylephrine. Labetalol (10(-7)-10(-5) M), MK-761 10(-7)-10(-5) M), timolol (10(-7)-10(-4) M) and propranolol (10(-6)-10(-4) M) relaxed both endothelium intact and denuded vessels in a dose-dependent manner. Spirendalol (2.8 X 10(-8)-8.1 X 10(-6) M), a specific beta-2 receptor antagonist and L643717 (1.8 X 10(-7)-3.6 X 10(-6) M), a specific beta-1 receptor antagonist did not elicit relaxation. Labetalol, MK-761, timolol and propranolol promoted relaxation only when vascular segments were preconstricted with phenylephrine or norepinephrine and failed to do so when prostaglandin F2 alpha or U46619 were used. This indicates a possible displacement of alpha adrenergic agonists with the beta antagonists. The degree of relaxation induced by labetalol, MK-761, timolol and propranolol was significantly less (P less than .05) when the endothelium was removed. Eicosatetraynoic acid (3.2 X 10(-5) M) significantly attenuated the relaxation response to labetalol, MK-761 and timolol in the intact but not in denuded vascular preparations. These studies suggest that some of the vascular effects of beta blockers may relate to the endothelium. PMID- 2879032 TI - Effects of chronic exposure to ethanol on the prostaglandin E1 receptor-mediated response and binding in a murine neuroblastoma clone (N1E-115). AB - With the use of cultured murine neuroblastoma cells (clone N1E-115), the authors studied the effects of chronic ethanol on prostaglandin E, (PGE1)-mediated cyclic AMP formation, adenylate cyclase activity and [3H]PGE1 binding. Whereas acute exposure of these cells to ethanol potentiates the PGE1 response, exposure of cells, for as little as 1 day, to 100 mM ethanol resulted in a diminished responsiveness to PGE1 compared with that in acutely treated cells. This apparent tolerance was well developed by day 4, and, by day 7, treated cells had a diminished response to PGE1 when assayed in the absence of ethanol. To achieve the same level of PGE1-mediated cyclic AMP synthesis as acutely exposed cells, chronically exposed cells required higher concentrations of ethanol. With 7 to 10 days of treatment, there was a modest (10-13%) increase in basal, PGE1- and forskolin-stimulated adenylate cyclase activity in membranous preparations, a 28 to 40% increase in high-affinity [3H]PGE1 binding to membranes with no change in Kd or in the ability of 5'-guanylimidodiphosphate to reduce this binding and a 155% increase in [3H]PGE1 binding to intact cells with no change in Kd. Thus, chronic exposure of N1E-115 cells to ethanol resulted in tolerance to its effects on the PGE1 receptor system, and this tolerance was accompanied by apparently paradoxical changes in PGE1-stimulated cyclic AMP synthesis and [3H]PGE1 binding. PMID- 2879034 TI - Dopamine1 receptor agonist and alpha-2 adrenoceptor antagonist effects of fenoldopam in rabbits. AB - Neurochemical and circulatory effects of fenoldopam were studied in pithed rabbits with electrically stimulated sympathetic outflow and in strips of the rabbit pulmonary artery. In pithed rabbits, fenoldopam (1-30 micrograms/kg/min) decreased the arterial blood pressure. Fenoldopam (3-30 microgram/kg/min) also increased the norepinephrine spillover rate (the rate at which endogenous norepinephrine enters into the plasma after having been released from postganglionic sympathetic nerves) and decreased the [3H]norepinephrine plasma clearance. The selective dopamine (DA)1 antagonist SCH 23390 (bolus injection of 10 micrograms/kg followed by infusion of 2 micrograms/kg/hr) antagonized markedly and the DA2-selective antagonist domperidone (bolus injection of 200 micrograms/kg followed by infusion of 50 micrograms/kg/hr) antagonized slightly the hypotensive effect. The increase in the norepinephrine spillover rate was enhanced after treatment with desipramine. Clonidine (0.3 microgram/kg/min) reduced the spillover of norepinephrine, and this effect was abolished by fenoldopam (30 micrograms/kg/min). In pulmonary artery strips preincubated with [3H]norepinephrine, fenoldopam (10(-7) and 10(-6) M) increased the electrically evoked overflow of tritium. The effect of fenoldopam (10(-6) M) was prevented in the presence of a supramaximal concentration of clonidine (10(-5) M). The results suggest that fenoldopam lowers blood pressure mainly by activation of vascular smooth muscle DA1 receptors. In addition, however, it blocks prejunctional alpha 2 autoreceptors at postganglionic sympathetic axons. PMID- 2879035 TI - Mechanisms of action of acetylcholine in the guinea-pig cerebral cortex in vitro. AB - The mechanisms of action of acetylcholine (ACh) in the guinea-pig neocortex were investigated using intracellular recordings from layer V pyramidal cells of the anterior cingulate cortical slice. At resting membrane potential (Vm = -80 to -70 mV), ACh application resulted in a barrage of excitatory and inhibitory post synaptic potentials (p.s.p.s) associated with a decrease in apparent input resistance (Ri). ACh, applied to pyramidal neurones depolarized to just below firing threshold (Vm = -65 to -55 mV), produced a short-latency hyperpolarization concomitant with p.s.p.s and a decrease in Ri, followed by a long-lasting (10 to greater than 60 s) depolarization and action potential generation. Both of these responses were also found in presumed pyramidal neurones of other cortical regions (sensorimotor and visual) and were blocked by muscarinic, but not nicotinic, antagonists. The ACh-induced hyperpolarization possessed an average reversal potential of -75.8 mV, similar to that for the hyperpolarizing response to gamma-aminobutyric acid (GABA; -72.4 mV) and for the i.p.s.p. generated by orthodromic stimulation (-69.6 mV). This cholinergic inhibitory response could be elicited by ACh applications at significantly greater distance from the cell than the slow depolarizing response. Blockade of GABAergic synaptic transmission with solution containing Mn2+ and low Ca2+, or by local application of tetrodotoxin (TTX), bicuculline or picrotoxin, abolished the ACh-induced inhibitory response but not the slow excitatory response. In TTX (or Mn2+, low Ca2+) the slow excitatory response possessed a minimum onset latency of 250 ms and was associated with a voltage-dependent increase in Ri. Application of ACh caused short-latency excitation associated with a decrease in Ri in eight neurones. The time course of this excitation was similar to that of the inhibition seen in pyramidal neurones. Seven of these neurones had action potentials with unusually brief durations, indicating that they were probably non-pyramidal cells. ACh blocked the slow after-hyperpolarization (a.h.p.) following a train of action potentials, occasionally reduced orthodromically evoked p.s.p.s, and had no effect on the width or maximum rate of rise or fall of the action potential. It is concluded that cholinergic inhibition of pyramidal neurones is mediated through a rapid muscarinic excitation of non-pyramidal cells, resulting in the release of GABA. In pyramidal cells ACh causes a relatively slow blockade of both a voltage-dependent hyperpolarizing conductance (M-current) which is most active at depolarized membrane potentials, and the Ca2+-activated K+ conductance underlying the a.h.p.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2879037 TI - Effects of calcium and magnesium on transmitter release at Ia synapses of rat spinal motoneurones in vitro. AB - The lumbar spinal cord excised from neonatal rats was superfused with an oxygenated saline, and monosynaptic excitatory post-synaptic potentials (e.p.s.p.s) were recorded from the lumbar motoneurones following stimulation of muscle nerves of the hind leg. The amplitude of monosynaptic e.p.s.p.s increased with an increase in the external Ca2+ concentration ([Ca2+]o). In [Ca2+]o of 0.5 2 mM, the relation between the e.p.s.p. amplitude and [Ca2+]o was linear with a slope of 1.6 on double logarithmic co-ordinates. An increase in [Mg2+]o in a range of 1-5 mM reduced the e.p.s.p. amplitude without affecting the slope of the relation between log e.p.s.p. amplitude and log [Ca2+]o, suggesting competitive interaction between Ca2+ and Mg2+. When [Ca2+]o was increased to 4-12 mM, the latency of monosynaptic e.p.s.p.s was prolonged, and the antidromic action potential failed to invade the cell body or initial segment of motoneurones. Under these conditions, the monosynaptic e.p.s.p.s were still present. It is concluded that at near-normal levels of [Ca2+]o the effects of Ca2+ and Mg2+ on the e.p.s.p. amplitude are accounted for entirely by their competitive interaction for the probability of transmitter release without altering the mode of impulse propagation at central terminals of the Group Ia sensory fibres. It is suggested that impulses of Ia sensory fibres normally invade their terminals without intermittent blocks at their terminal branch points. PMID- 2879036 TI - Amino acid receptor mediated excitatory synaptic transmission in the cat red nucleus. AB - A study has been made of the effects of the selective N-methyl-D-aspartate receptor antagonist, 2-amino-5-phosphonovalerate (APV), and the broad spectrum excitatory amino acid antagonists, gamma-D-glutamylglycine (gamma-DGG), gamma-D glutamylaminomethylsulphonate (GAMS), 4(p-chlorobenzoyl)-cis-piperazine-2, 3 dicarboxylate (pCB-PzDA) and kynurenate, have been examined on excitation evoked on neurones in the magnocellular red nucleus (m.r.n.) of the anaesthetized cat by stimulation of the interpositus nucleus (i.p.n.) and sensorimotor cortex, and by ionophoresed excitant amino acid agonists. The profile of activity of the excitatory amino acid antagonists on m.r.n. neurones was similar to that described on neurones in other areas of the central nervous system. APV selectively depressed responses to N-methyl-D-aspartate (NMDA), whereas the broader spectrum antagonists reduced responses to kainate and quisqualate as well as to NMDA. Neuronal responses to L-glutamate and L-aspartate were depressed by all the antagonists tested. I.p.n.-evoked monosynaptic responses of m.r.n. neurones were reversibly reduced by the broad spectrum antagonists, but were unaffected by APV. Cortically evoked mono- and polysynaptic excitatory responses were reversibly depressed by APV and the broad spectrum antagonist, pCB-PzDA. The action of APV corresponded with its ability to antagonize responses to NMDA. However, the cortically evoked responses appeared to be more sensitive to the actions of pCB-PzDA than to those of APV, although the former is a less effective antagonist of NMDA-induced excitation compared with APV. APV depressed excitation induced by cortical stimuli and L-glutamate and L-aspartate. However, there was no obvious correlation between the actions of the broad spectrum amino acid antagonists on synaptically evoked responses and those induced by L-glutamate or L-aspartate on the few neurones tested. These results are consistent with an amino acid being the transmitter in the interposito-rubral and cortico-rubral excitatory pathways which interacts with non-NMDA and both NMDA and non-NMDA receptors respectively. However, the identity of the transmitter acting at these receptors remains to be determined. PMID- 2879039 TI - Discharge patterns of cervical sympathetic preganglionic neurones related to central respiratory drive in the rat. AB - The central respiratory-drive-related inputs to antidromically identified cervical sympathetic preganglionic neurones have been investigated, in the rat, using extracellular recording techniques, the ionophoretic application of an excitatory amino acid (glutamate) to increase their excitability, and phrenic nerve discharge as an indicator of central respiratory drive. Three distinct firing patterns of sympathetic preganglionic neurones are described: maximal discharge during phrenic nerve activity, maximal discharge during phrenic silence, and a firing pattern unrelated to phrenic nerve discharge. Both spontaneously active and glutamate-activated silent cervical sympathetic preganglionic neurones had similar, if not identical, firing patterns. The application of glutamate, using ionophoretic currents of up to 100 nA, did not disrupt central respiratory-drive-related discharge patterns indicating that these inputs are an important contribution in the regulation of the firing pattern of a proportion of sympathetic preganglionic neurones. On the basis of these observations it is proposed that some sympathetic preganglionic neurones may receive central respiratory drive potentials similar to those received by respiratory motoneurones. PMID- 2879038 TI - Correlation between long-term potentiation and release of endogenous amino acids from dentate gyrus of anaesthetized rats. AB - The relationship between long-term potentiation (l.t.p.) and the release of endogenous amino acid transmitters has been investigated in the dentate gyrus of rats anaesthetized with urethane. The molecular layer was perfused with artificial cerebrospinal fluid using a push-pull cannula. The perfusate was collected and analysed for glutamate, aspartate, glycine, glutamine and gamma aminobutyric acid (GABA) using high-performance liquid chromatography (h.p.l.c.) with fluorometric detection. Recording electrodes were attached to the cannula to enable responses evoked by test stimuli to the perforant path to be monitored in the molecular and cell body layers. Perfusion was continued for 3 h while test stimuli were delivered to the perforant path at 30 s intervals. In the control group (n = 8), no further stimulation was given. In a second group (n = 8), a single high-frequency train (250 Hz for 200 ms) was delivered at the end of the first hour to induce l.t.p. The average potentiation of the slope of the excitatory post-synaptic potential (e.p.s.p.) 2 h later was 15%. In a third group (n = 8), the train to the perforant path was paired with a train to the commissural input to the dentate gyrus, a procedure which blocks the induction of l.t.p. In the potentiated group, there was an increase in the concentrations of glutamate and aspartate following the induction of l.t.p., relative to the decline seen in corresponding periods of the control group. This increase remained statistically significant for 1.5 h in the case of glutamate and for 45 min in the case of aspartate. There were no l.t.p.-associated changes in the release of glutamine or glycine; there was an indication that l.t.p. may be associated with a decrease in the release of GABA. Increasing the frequency and intensity of perforant path activation resulted in enhanced concentrations of glutamate and aspartate in the perfusate; no such changes occurred when granule cells were activated antidromically. We discuss the origin of the relative increases in the concentration of glutamate and aspartate which are found in the perfusate following the induction of l.t.p. and conclude that the most likely source is a sustained increase in activity-dependent release of these amino acids from perforant path terminals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2879040 TI - Effects of chloropyramine, dimethindene and diphenhydramine on transepithelial ion transport: studies in bovine tracheal epithelium and frog skin. AB - The effects on transepithelial ion transports of chloropyramine, dimetindene and diphenhydramine, which are three antagonists of H1-receptors of histamine, were examined in bovine tracheal epithelium and in frog skin. The short-circuit current I0 across bovine tracheal epithelium is the sum of active secretion of Cl and absorption of Na+. In this tissue, all three drugs induced a reversible, dose-related inhibition of I0, up to 100%. The concentrations giving 50% of maximal effect were 1.4 X 10(-4) M for chloropyramine, 2.0 X 10(-4) M for dimetindene and 2.5 X 10(-4) M for diphenhydramine. The effect was unrelated to the agonist binding site of H1-receptors of histamine, since it was not altered in the presence of 10(-3) M histamine. Experiments in which Na+ transport was selectively reduced by 5 X 10(-5) M amiloride, or in which Cl- transport was selectively abolished by 10(-3) M furosemide, 10(-4) M bumetanide or Cl- removal, indicated that Na+ and Cl- transports were equally affected by the drugs. The action of chloropyramine was composed of an early inhibition of Na+ and Cl- movements, followed by a slow recovery of Cl- secretion. In frog skin, each one of the three H1-antagonists modified the I0, following two main patterns of response, a stimulation at the lower concentrations tested, or an inhibition at higher concentrations. Dose-response relationships were obscured by a large variability in response of individual skins. These observations in bovine tracheal epithelium and frog skin suggest that H1-antagonists might alter the functioning of other epithelia as well. PMID- 2879041 TI - Metoclopramide in schizophrenia (an open study). PMID- 2879042 TI - [Unusual echographic aspects of hepatic distomiasis]. AB - The authors report, a pediatric case of hepatic fascioliasis with an unusual ultrasonographic aspect; that is a hypoechoic intrahepatic nodule with an extrahepatic prolongation through a thickened capsule. This ultrasonographic appearance, which has not been reported in the literature to our knowledge, seems to reflect the parasite migration. PMID- 2879043 TI - An ecological study of Jamestown Canyon virus on the Delmarva Peninsula, with emphasis on its possible vector. PMID- 2879044 TI - Acquisition of a gene encoding mannose-resistant haemagglutinating fimbriae by a resistance plasmid during long-term urinary infection. AB - Urine was collected twice weekly from one patient during a 25-month period. Escherichia coli harbouring a resistance plasmid, pUK28, which confers trimethoprim, ampicillin, sulphamethoxazole, spectinomycin and streptomycin resistance was identified in the urine. Carriage of strains containing plasmid pUK28 was observed during three separate periods which totalled 16 months, even though the patient did not receive antibacterial drug therapy for most of that time. The plasmid was able to acquire the genes responsible for mannose-resistant haemagglutination and these genes were increasingly associated with the plasmid towards the end of the study period. PMID- 2879045 TI - Mosquito control by plankton management: the potential of indigestible green algae. AB - Most kinds of phytoplankton are good food for mosquito larvae. However, Culex, Aedes and Anopheles larvae fail to develop successfully in water where certain species of closely related green algae in the order Chlorococcales are the main source of food; apparently because the larvae are unable to digest them. Many species of Scenedesmus, Kirchneriella, Dactylococcus, Elakotothrix, Tetrallantos, Coelastrum, Selenastrum and Tetradesmus have this effect. These algae may offer a practical possibility for mosquito control when introduced into mosquito breeding habitats. Introduction of these algae could be assisted by simultaneous introduction of select filter-feeding zooplankton such as Daphnia. PMID- 2879046 TI - Fertility in cryptorchidism: further development of an experimental model. AB - Further development of an experimental model for evaluating fertility in cryptorchidism led to studies of unilateral cryptorchidism, endocrinological cryptorchidism, and the effects of treatment. The results demonstrate that rats with unilateral mechanical cryptorchidism have a significant diminution in the ability to impregnate females (impregnation rate, 45%) when compared with sham operated controls (84%) and rats undergoing unilateral orchiectomy (88%). In addition, we demonstrated that lower doses of estradiol caused cryptorchidism and resulted in infertility of approximately the same degree as higher doses (impregnation rates, 18% and 0%, respectively), but avoided obvious side effects. Treatment of estradiol-induced cryptorchidism with human chorionic gonadotropin resulted in testicular descent, but did not significantly improve the ability to bear offspring (10% with hCG vs. 0% without). Surgical orchiopexy after surgically induce mechanical cryptorchidism resulted in improved fertility (30% vs. 0%); however, the improvement was still significantly less than the control rate. In summary, this experimental model demonstrates the effects of various aspects of cryptorchidism and its treatment on fertility and can easily be adapted to evaluate important clinical problems. PMID- 2879047 TI - Prune belly syndrome: 35 years of experience. AB - Between 1949 and 1984, 50 children with the prune belly syndrome were treated at our institution. The modes of evaluation and treatment, and the long-term results are discussed. PMID- 2879048 TI - Nocturnal ulcer pain relief from tricyclic antidepressants. PMID- 2879049 TI - [Chemical structure of the bacterial cell surface]. PMID- 2879051 TI - [Pertussis]. PMID- 2879050 TI - [Adhesion and colonization of pathogens--special reference to enterotoxigenic E. coli]. PMID- 2879052 TI - [Biochemical and histochemical studies on variant gamma-glutamyl transpeptidase (GGT) in human gastric cancer]. PMID- 2879053 TI - Activation of lateral vestibular nucleus neurons by iontophoretically applied phencyclidine. AB - Microiontophoretic studies were performed to elucidate the effects of phencyclidine (PCP) on neuronal activity in the lateral vestibular nucleus (LVN) of cats anesthetized with alpha-chloralose. Spikes elicited in the monosynaptic LVN neurons by vestibular nerve stimulation were not affected by iontophoretic application of PCP up to 100 nA, but they were blocked by atropine (30-50 nA). A dose-dependent increase in spontaneous firing during application of PCP was obtained in 11 of 15 monosynaptic neurons, in all of which firing was increased by iontophoretically applied acetylcholine (ACh). Simultaneous application of atropine completely inhibited the PCP- and ACh-induced increase in the firing without affecting the glutamate-induced firing. These results indicate that PCP acts on the LVN monosynaptic neurons receiving input from the vestibular nerve in a similar manner to ACh. PMID- 2879054 TI - Potentiation of haloperidol-induced catalepsy by beta-adrenoceptor antagonists in mice. AB - Several clinical papers have reported that beta-adrenoceptor antagonists were useful in the management of schizophrenia and tardive dyskinesia. The present study examined effects of beta-antagonists on haloperidol (HAL)-induced catalepsy using mice in order to study the relationship between beta-antagonists and central dopaminergic functions. Catalepsy was tested by the standard bar test 30 min after intraperitoneal treatment of HAL. Beta-antagonists were administered subcutaneously just after HAL-treatment. Propranolol, alprenolol, oxprenolol and pindolol increased the incidence of catalepsy compared to HAL alone. Atenolol, not penetrating into the brain, and the sedative and hypnotic drug chlordiazepoxide did not potentiate it. These results suggest that the potentiation of HAL-catalepsy by beta-antagonists is based on their central action. Therefore, a central beta-receptor appears to be implicated in the regulation of the central dopaminergic functions. PMID- 2879055 TI - Cardiohemodynamic effects of nipradilol (K-351) in the dog: comparison with propranolol, nadolol and prazosin. AB - The cardiohemodynamic effects of nipradilol (K-351) were studied in comparison with those of propranolol, nadolol and prazosin in anesthetized, open-chest dogs. All drugs were administered intravenously. Nipradilol produced dose-dependent decreases in systemic blood pressure (BP), heart rate (HR), venous return (VR) and cardiac output (COP), but virtually no change in right atrial pressure (RAP). Propranolol decreased HR, tended to decrease VR and COP and increased RAP, but produced no change in systemic BP. Nadolol also decreased HR, VR and COP and increased RAP, but did not change systemic BP. Prazosin decreased systemic BP, VR and COP and tended to decrease RAP, but scarcely affected HR. After propranolol or nadolol, nipradilol failed to reduce HR, but still produced definite decreases in systemic BP, VR and COP and a slight decrease in RAP. After prazosin, nipradilol still produced decreases in systemic BP, HR, VR and COP. These results suggest that nipradilol decreases VR and COP mainly by increasing venous capacitance through direct venodilator action and in part by increasing resistance to VR through beta-adrenoceptor blockade. This effect also appears to be responsible for its hypotensive effect. PMID- 2879056 TI - Some profiles of transmucosal potential difference in rat stomach determined in situ with special reference to effects of timoprazole, a H+,K+-ATPase inhibitor. AB - Gastric transmucosal potential difference (PD) is referred to an index of function and integrity of the mucosa. The features of gastric PD were studied in association with gastric acid secretion. The gastric PD was measured at the forestomach, glandular portion and pylorus in the rat in in situ preparations. Secretagogues such as bethanechol (BeCh, 50 micrograms/kg, i.v.), tetragastrin (TG, 30 micrograms/kg, i.v.), and histamine (Hist, 10 mg/kg, s.c.) produced a decrease in PD at the three regions of the stomach. These PD reductions did not occur with the combined treatment with timoprazole (30 mg/kg, i.d.); a marked increase in PD was noted, especially, in the case of Hist plus timoprazole. Similarly, BeCh induced PD decrease was antagonized by atropine (30 micrograms/kg, i.v.) and Hist induced PD decrease was attenuated by cimetidine (10 mg/kg, i.v.), while TG induced PD decrease was not affected by either of them. Of the antisecretory drugs, only cimetidine produced an increase in basal PD, probably via a mechanism unrelated to acid secretion. These results suggest that the PD decrease by each secretagogue seen at oxyntic and non-oxyntic gland regions of the stomach primarily originates from secretory activation of the parietal cells and that its action on function unrelated to acid secretion also exerts a minor influence on gastric PD. PMID- 2879057 TI - Pharmacological studies of 2-(3-(3-(1-piperidinylmethyl)-phenoxy)propylamino)-4 (3H)-quinazolinone (NO-794), a new histamine H2-receptor antagonist. AB - The pharmacological profile of a new histamine H2-receptor antagonist, 2-(3-(3-(1 piperidinylmethyl)phenoxy)propylamino)-4 (3H)-quinazolinone (NO-794), was studied. NO-794 was a potent and selective histamine H2-receptor antagonist in the guinea-pig atria and gastric mucosal cells. NO-794 (1 X 10(-5) M) did not interact with H1-, muscarinic and beta 1-receptors. In guinea-pig atria, antagonism of NO-794 was unsurmountable. The onset of action of NO-794 was slow, and this antagonism was apparently irreversible not only on the guinea-pig atria but also on the gastric mucosal cells. In addition, NO-794 inhibited gastric acid secretion in pylorus ligated rats when administered intraduodenally. These results indicate that NO-794 is a powerful and unique histamine H2-receptor antagonist and may be useful in the treatment of peptic ulcer. PMID- 2879058 TI - Difference in mode of action of alpha 1-adrenoceptor antagonists on some vascular smooth muscles and efficacy. AB - Effect of YM-12617, a selective and potent alpha 1-adrenoceptor antagonist on dose-response curves of alpha 1-adrenoceptor agonists, norepinephrine, phenylephrine and naphazoline, was tested in isolated rabbit vascular smooth muscles such as the femoral vein, portal vein and aorta. YM-12617 shifted the dose-response curves for norepinephrine and phenylephrine to the right and also declined the maximum response in the femoral vein, where norepinephrine and phenylephrine behaved as low efficacy agonists. Similar results were obtained on the curve of naphazoline in the portal vein, where the efficacy of naphazoline was low. However, the efficacies of norepinephrine, phenylephrine and naphazoline were high in the aorta. The dose-response curves for three alpha 1-agonists were shifted by YM-12617 in a parallel manner in the aorta. The curves of norepinephrine and phenylephrine were also shifted by YM-12617 in the portal vein, where the efficacies of both the alpha 1-agonists were high. The present results suggest that the mode of antagonism between the alpha 1-agonist and alpha 1-antagonist is dependent on the efficacy of the alpha 1-agonist which depends upon the receptor-density in the organ used. PMID- 2879059 TI - Studies on responsiveness of hepatoma cells to catecholamines. III. Difference between the receptor-adenylate cyclase regulating systems in AH130 cells and cultured normal rat liver cells. AB - The responsiveness to three beta-adrenergic agonists, isoproterenol (IPN), epinephrine (Epi) and norepinephrine (NE) in AH13O cells was examined compared with that in normal rat liver cells which were cultured for 24 hr after collagenase digestion. As regards to the activation of adenylate cyclase in the cell homogenates, the relative affinity of the three agonists was in order of IPN greater than NE greater than Epi in AH130 cells and IPN greater than Epi greater than NE in cultured normal liver cells. While the efficacies of the three agonists were similar in cultured liver cells, those of NE and Epi were markedly lower than that of IPN in AH13O cells and were increased to the similar level of IPN by pretreatment with phentolamine, but not with prazosin. Clonidine inhibited the activation of adenylate cyclase by IPN in AH13O cells. When cells were preincubated with islet-activating protein (IAP), the activity of adenylate cyclase in the presence or absence of agonist in both cell lines increased. In IAP-treated AH13O cells, the efficacies of NE and Epi became close to that of IPN. Adenylate cyclase in IAP-treated AH13O cells was activated by GTP in a dose dependent manner, but that in IAP-treated cultured liver cells was not. In the presence of IPN, biphasic (activatory and inhibitory) effects of GTP on the cyclase were observed, and the inhibitory phase was eliminated by the IAP treatment in both cell lines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879060 TI - Endothelium-dependent changes in the response to vasoconstrictor substances of isolated dog mesenteric veins. AB - In dog mesenteric vein strips, contractions induced by histamine relative to those induced by 5 mM Ba++ were potentiated by removal of endothelium. The induced contractions were potentiated by AA861, a lipoxygenase inhibitor, and methylene blue, a guanylate cyclase inhibitor, to an appreciably greater extent in the strips with endothelium than in those with damaged endothelium. Indomethacin did not potentiate the contraction induced by histamine. Cimetidine potentiated the contraction in control strips and those without endothelium to a similar extent whereas chlorpheniramine suppressed the contraction. Contractile responses to acetylcholine, norepinephrine, serotonin and prostaglandin (PG) F2 alpha were not potentiated by removal of endothelium. It may be concluded that histamine activates histaminergic receptors, possibly H1 but not H2, in endothelial cells and results in a release of vasodilator substance produced by lipoxygenase, which accumulates cellular cyclic GMP and relaxes mesenteric veins. The H1 and H2 receptors in smooth muscle cells appear to be responsible for contractions and relaxations, respectively. Acetylcholine, norepinephrine, serotonin and PGF2 alpha do not seem to release vasodilator substances from endothelium in an amount sufficient to cause significant relaxations of venous smooth muscle. PMID- 2879061 TI - A beta-adrenergic partial agonist (befunolol) discriminates two different affinity sites. AB - Interactions of beta-adrenergic partial agonists with the beta-adrenoceptor were studied in isolated guinea-pig taenia caecum. The competitive inhibition curve for specific binding of a high concentration (50 nM) of [3H]-befunolol by befunolol showed a biphasic shape, although the curve for specific binding of a low concentration (1 nM) was monophasic. All the competitive inhibition curves for specific binding of [3H]-befunolol (1 nM and 50 nM) by isoprenaline and propranolol showed monophasic shapes. These results suggest that befunolol may be able to discriminate two different binding sites of the beta-adrenoceptor: the high affinity site and the low affinity site. PMID- 2879062 TI - [Receptive relaxation of the canine stomach]. AB - Receptive relaxation of the stomach by feeding was studied in 5 conscious dogs by means of chronically implanted force transducers on the gastric body and antrum. It was found that only the gastric body but not antrum relaxed by feeding, and magnitude of the relaxation of the gastric body was linearly related to the volume (5, 10 and 20 g/kg) of test meals, given once or in multiple times. Secondly, in the study of pharmacological blockers, it was found that atropine, hexamethonium and phentolamine significantly inhibited relaxation, while naloxone and proglumide significantly suppressed relaxation in 3 dogs. Propranolol and domperidone did not influence on receptive relaxation. It is concluded that receptive relaxation of the stomach is mainly mediated through a cholinergic reflex, however, involvement of neurotransmitters other than acetlycholine is suggested in the regulation of receptive relaxation. PMID- 2879063 TI - Glucagon: a first-line drug for cardiotoxicity caused by beta blockade. PMID- 2879064 TI - Mechanisms of action of atrial natriuretic factor: clinical consequences. AB - Atrial natriuretic factor (ANF) acts through specific receptors at its target tissues. Receptor-occupancy by ANF induces activation of particulate guanylate cyclase, increased cyclic GMP formation and also inhibition of adenylate cyclase which results in a decrease of cyclic AMP formation. These second messenger systems appear to mediate the effects of ANF in target tissues. Following receptor-mediated activation of particulate guanylate cyclase, cyclic GMP is extruded from the cells, which leads to elevated cyclic GMP levels in plasma and urine in man, whereas cyclic AMP levels remain unchanged. Since cyclic GMP has a much longer half-life than ANF, it is more sensitive as a marker for ANF release than ANF itself, which has a half-life of just a few minutes. Since cyclic GMP is excreted into urine, determinations of urine cyclic GMP can also allow conclusions about the ANF system when blood sampling is impractical. Thus, cyclic GMP and not cyclic AMP is a sensitive biological marker for ANF. PMID- 2879065 TI - Transmembrane signalling of atrial natriuretic peptide in rat renal juxtaglomerular cells. AB - Recently we have shown that atrial natriuretic peptide (ANP) inhibits renin release from isolated rat renal juxtaglomerular (JG) cells. ANP in general is thought to act on its target cells by the binding to specific membrane receptors. It is the objective of this contribution to summarize our present knowledge about the sequence of events by which the occupancy of ANP receptors could lead to an inhibition of renin release from juxtaglomerular (JG) cells. It was found that ANP did not affect the intracellular concentration of calcium. ANP led to a dose dependent increase in the intracellular concentration of cyclic GMP and to a dose dependent decrease of cAMPi. Inhibition of renin release from the JG-cells by ANP was clearly correlated to the level of cGMPi and not to the level of cAMPi. Concerning the mechanism by which ANP causes a rise in cGMPi in JG-cells it was found that the effect of ANP on cGMPi was potentiated by the cGMP phosphodiesterase specific inhibitor M & B 22,948. This finding suggests that ANP enhances cGMPi by the stimulation of a guanylate cyclase rather than by the inhibition of a cGMP phosphodiesterase. Moreover, evidence was obtained that the effect of ANP on cGMP, was markedly attenuated after pretreatment of the JG-cells with pertussis toxin. Since pertussis toxin is considered to inactivate guanine nucleotide binding proteins (G-proteins), this result could indicate that ANP receptors are coupled to a guanylate cyclase via a G-protein. Experimental evidence suggests that the G-protein in question might be the inhibitory unit (Ni) of the adenylate cyclase. PMID- 2879066 TI - [Work Group of European Nurse Researchers and its conference on nursing research and care: the meeting at Helsinki]. PMID- 2879068 TI - Examination of enzyme-altered foci with gamma-glutamyl transpeptidase, aldehyde dehydrogenase, glucose-6-phosphate dehydrogenase, and other markers in methacrylate-embedded liver. AB - F344 Male rats weighting between 90 and 110 gm were given 90 ppm diethylnitrosamine in their drinking water for 5 weeks. Seven weeks after the administration of carcinogen was completed, the rats were sacrificed and sections of their livers were embedded in methacrylate. Serial sections 2 or 4 micron in thickness demonstrated the presence of gamma-glutamyl transpeptidase, acid phosphatase, adenosine triphosphatase, aldehyde dehydrogenase, alkaline phosphatase, alpha-naphthyl butyrate esterase, DT diaphorase, glucose-6-phosphate dehydrogenase, and 5'-nucleotidase activity and glycogen. The use of 4-micron sections of methacrylate-embedded tissue allows the evaluation of many more phenotypic markers in serial sections than is currently possible with frozen sections. PMID- 2879067 TI - Restriction fragment length polymorphisms in the 5' end region of the human argininosuccinate synthetase gene. PMID- 2879071 TI - Patency of internal mammary artery grafts in no-flow situations. AB - We report two cases in which an internal mammary artery graft was found to be nonfunctional in the early postoperative period, but repeat catheterization at 6 months revealed the graft to be patent. These two cases substantiate that closure of an internal mammary artery graft may be reversible. PMID- 2879070 TI - [Demonstration of anxiolytic action using "psychic" stress (stress caused by noise)]. PMID- 2879069 TI - Direct versus reflex activation of cardiac beta-adrenoceptors in the chronotropic and inotropic effects of isoprenaline and prenalterol in the conscious dog. AB - The mechanisms by which isoprenaline and prenalterol increase heart rate and myocardial contractile force were investigated in conscious instrumented dogs. Isoprenaline (0.1 micrograms/kg/min/10 min) increased both heart rate (+98 +/- 14%) and contractility (+36 +/- 5%) and decreased diastolic blood pressure. beta 1-Adrenoceptor blockade abolished the isoprenaline induced increase in contractility whereas the induced tachycardia was reduced by approximately 50%. Either beta 2-blockade, which abolished the hypotensive effect of isoprenaline or ganglionic blockade, which abolished the isoprenaline-induced activation of sino aortic baroreflexes, strongly reduced (-67 +/- 8%) the isoprenaline-induced tachycardia but did not markedly alter the increase in contractility. However, the isoprenaline-induced increase in contractility was potentiated by methylatropine (+83 +/- 12%) whereas the simultaneous tachycardia was less marked than before methylatropine. In the same dogs, prenalterol (2 micrograms/kg/min/5 min) increased contractility (+38 +/- 5%) to the same extent as isoprenaline but induced a lesser increase in heart rate (+23 +/- 3%) and had no effect on aortic pressure. These effects were not significantly modified by pretreatments with either ganglionic or beta 2-blockades but were abolished by beta 1-blockade. After methylatropine the prenalterol-induced increase in heart rate was not modified but the increase in contractility was potentiated (+63 +/- 11%). We conclude that whereas indirect activation of arterial baroreflexes through hypotension markedly contributes to the isoprenaline-induced increase in heart rate, the simultaneous increase in cardiac inotropism is only dependent upon direct beta 1-adrenoceptor activation by isoprenaline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879072 TI - A bibliography of the leukaemias in Africa, 1904-1985. AB - A bibliography of leukaemias in Africa is presented from 1904 to 1985. The literature is listed chronologically and is classified geographically (north, south, east and west Africa) and by leukaemia type. The epidemiology of leukaemias in Africa is discussed briefly, especially as to the rarity of acute lymphoblastic leukaemia under the age of four years, the frequency of chloroma, the young age of presentation of chronic granulocytic leukaemia, the frequency of chronic lymphatic leukaemia in adults, especially women, under 45 years in tropical Africa, and the frequency of infection by the human T-cell leukaemia lymphoma (or lymphotropic) virus type I and of adult T-cell leukaemia-lymphoma. PMID- 2879073 TI - Chromosomal abnormalities in a patient with smoldering adult T-cell leukemia: evidence for a multistep pathogenesis. AB - A cytogenetic study was performed on peripheral blood cells from a patient with smoldering adult T-cell leukemia (ATL). Four types of primary abnormal clones were found upon examination of a large number of karyotypically analysed cells cultured with and without phytohemagglutinin (PHA). However, human T-cell leukemia virus (HTLV) proviral DNA was confirmed to be monoclonal. This discrepancy can be explained by the hypothesis that these four primary abnormal clones were all derived from a leukemic clone with a normal karyotype and the same integration site of HTLV proviral DNA. PMID- 2879074 TI - Dissociation of interleukin-2-mediated cell proliferation and interleukin-2 receptor upregulation in adult T-cell leukemia cells. AB - We studied cell proliferation and interleukin-2 (IL-2) receptor upregulation mediated by exogenous IL-2 in leukemic cells from adult T-cell leukemia (ATL) patients to characterize some aspects of abnormal IL-2 receptor expression in ATL. Leukemic cells from 7 ATL patients examined showed no or very poor proliferative response to IL-2 though they expressed IL-2 receptors without any stimulation. In contrast, ATL leukemic cells cultured with IL-2 for 2 days expressed about twice as many IL-2 receptors as those of cells cultured without IL-2. Thus, in ATL leukemic cells, there seems to be a dissociation between the signal(s) for two different effects mediated by IL-2, cell proliferation and IL-2 receptor upregulation. PMID- 2879075 TI - Physiopathological studies on granulocyte-macrophage colony stimulating factor and multi colony stimulating factor producing leukemia, L8313, induced by irradiation of C3H mice. AB - Radiation-induced L8313 leukemia bearing mice (L8313 mice) had marked granulocytosis with splenomegaly. Hemopoietic stem cells and progenitors increased in the spleen but not in the bone marrow. Spleen conditioned-medium and serum from L8313 mice induced the formation of granulocyte-macrophage colonies (CFU-GM), erythroid bursts (BFU-E) and mixed colonies (CFU-Mix). Bone marrow conditioned medium did not show such activity. A cell line (STIL-3) was established from the spleen cells of L8313 mice. Surface marker analysis showed that the established cells were suppressor T cell. The cells produced IL-3 and GM CSF in vitro, and induce essentially the same "leukemic" response in recipient mice. Inoculation of STIL-3 in diffusion chamber also induced leukemoid reaction, i.e. a marked granulocytosis with splenomegaly. Therefore, L8313 leukemia may be linked to an abnormality of growth and production of hemopoietic factors in hemopoietic regulatory cells. PMID- 2879076 TI - Quantitative autoradiography of transmitter binding sites with an image analyzer. AB - A computerized image processing system for quantitative receptor autoradiography on tritium-sensitive film is described. The method implements an image analyzer (IBAS 1 + 2) for the acquisition of an image which is evaluated with respect to the regional distribution of binding site densities by a small computer which is connected to a digitizer. Several methodological problems must be considered when using tritium-labelled compounds and an image analyzer. The use of tissue standards and shading procedures, the improvement of signal-to-noise ratio, the calibration of the system which establishes the non-linear relation between grey values and concentration of radioactivity, the contrast enhancement and the quenching problem are discussed. This method permits a quick and precise quantitative analysis of binding site distribution in receptor autoradiography. PMID- 2879078 TI - [Further development of the fibula-pro-tibia method in the treatment of tibial fractures and pseudarthrosis]. PMID- 2879077 TI - Rapid method for micro-analysis of endogenous amino acid neurotransmitters in brain perfusates in the rat by isocratic HPLC-EC. AB - A simplified method is described for the isocratic analysis of endogenous amino acid neurotransmitters contained in brain perfusates by high performance liquid chromatography (HPLC) with electrochemical detection (EC). Pre-column o phthalaldehyde (OPA) tert-butylthiol derivatives of the amino acids were injected into a C18 3 microns column. After linear concentration curves for standard solutions were obtained, the content of 6 amino acid neurotransmitters was analyzed in push-pull perfusates obtained from the hypothalamus and cerebral cortex of the unrestrained rat. Each analysis which included the simultaneous quantification of aspartic acid, glutamic acid, glutamine, glycine, taurine and gamma-aminobutyric acid (GABA), was completed in less than 15 min. The sensitivity of the assay ranged from 1.0 to 5.0 pmol of each amino acid contained within a 20 microliters aliquot of each perfusion sample. PMID- 2879079 TI - [Experience with the treatment of fractures combined with vascular injuries]. PMID- 2879080 TI - [Surgical management of mandibular fractures using metal plates]. PMID- 2879081 TI - [Experience with the surgical management of os tibiale externum]. PMID- 2879082 TI - [Reconstruction of flexor tendon injuries of unfavorable prognosis by transplantation of an autologous tendon-tendon sheath unit in the "no-man's land" of the hand]. PMID- 2879083 TI - [Traffic injuries of pedestrians]. PMID- 2879084 TI - [Vertebral osteomyelitis following gluteal abscess]. PMID- 2879086 TI - [Primary multiple osteogenic sarcoma]. PMID- 2879085 TI - [Benign bone tumor of rare localization causing a circulatory disorder in the lower extremity]. PMID- 2879087 TI - [Fat necrosis, caused by seat belt injury, simulating breast cancer in a poly traumatized patient]. PMID- 2879088 TI - [The first cases of femoral neck nailing in Hungary. In memoriam Laszlo Monszpart]. PMID- 2879089 TI - [Unrecognized primary subcutaneous rupture of the Achilles tendon]. PMID- 2879091 TI - The frequency of epilepsy preceding stroke. Case-control study in 230 patients. AB - In a case-control study, evidence of previous epilepsy was sought in 230 consecutive patients under the age of 70 admitted to hospital with acute stroke. 8 (4.5%) of the 176 patients having their first stroke were epileptic, compared with 1 (0.6%) of the matched controls. 6 of the 8 epileptics started their seizures after the age of 30 years. 5 (9.3%) of the 54 patients who had had a previous stroke were epileptic, compared with none of the control patients. The findings support the idea that otherwise clinically undetectable cerebrovascular disease may present with seizures and that these can be a warning sign for a future stroke. PMID- 2879090 TI - Laboratory testing on cerebrospinal fluid. A reappraisal. AB - 555 consecutive cases in which cerebrospinal fluid (CSF) was sent for cell count were reviewed to determine which cerebrospinal-fluid tests affect diagnosis or therapy. Among 334 cases (60%) with a normal opening pressure, cell count, and protein, 1385 additional tests were done, but such tests were useful in only 3 patients (0.9%) with multiple sclerosis. Among 148 consecutive cases of bacterial, chronic infectious, and malignant meningitis the opening pressure, cell count, or protein was abnormal in all but 3 (2 childhood bacterial meningitis and 1 cryptococcal meningitis in a patient with the acquired immunodeficiency syndrome). If the opening pressure, cell count, and protein are normal, no additional CSF tests are needed in most instances; however, in immunocompromised patients and in those with possible multiple sclerosis or childhood bacterial meningitis additional tests may be indicated. PMID- 2879092 TI - Effect of radiotherapy on symptoms due to heterotopic marrow in beta thalassaemia. AB - 8 thalassaemic patients with complications due to pressure by heterotopic marrow on the spinal cord, the vertebral column, or the airways were given radiotherapy. Small doses of radiotherapy (10 to 26 Gy) relieved symptoms in all of them. 3 of the patients were followed-up radiographically. In 2 the mass of heterotopic marrow regressed completely and in the other partially. PMID- 2879093 TI - Enhancement of in-vitro human interleukin-1 production by sodium acetate. AB - Human blood monocytes were incubated in vitro in the presence of various concentrations of sodium acetate or sodium chloride or with medium alone. Intracellular and extracellular levels of interleukin-1 (IL-1) were measured. The production of intracellular IL-1 and the release of extracellular IL-1 were higher in the presence of acetate than in the presence of chloride or in medium alone. The concentrations of acetate used were comparable to those encountered by blood monocytes on the surface of haemodialysis membranes. Since complications of peritoneal dialysis, such as loss of ultrafiltration and progressive fibrosis of the peritoneum, have been associated with the use of sodium acetate as the exchange-fluid buffer, these results suggest that the widespread use of sodium acetate as a buffer during haemodialysis may be contraindicated. PMID- 2879094 TI - Change and progress in uveitis. PMID- 2879095 TI - Man, dogs, and hydatid disease. PMID- 2879096 TI - Unexplained stillbirth. PMID- 2879097 TI - What has happened to carbohydrate intolerance following gastroenteritis? PMID- 2879098 TI - Diagnosis of cystic fibrosis in premature infants. PMID- 2879099 TI - Sacral root stimulation for bladder control. PMID- 2879100 TI - Knowledge, attitudes, and behaviour of health professionals in relation to AIDS. PMID- 2879101 TI - Very-low-dose hepatitis B vaccine in newborn infants: an economic option for control in endemic areas. AB - Three 1 microgram or 2 micrograms doses of Merck, Sharp and Dohme plasma vaccine were given to 119 infants of mothers negative for antibody to hepatitis B surface antigen (anti-HBs). Anti-HBs antibodies developed in 25/29 (86%) infants given 1 microgram and in 86/90 (96%) given 2 micrograms doses. Levels of anti-HBs achieved by three 2 micrograms doses were similar to those that have been reported for conventional 10 micrograms doses. Similar levels were recorded from infants of anti-HBs-positive mothers, which suggests that maternal antibody does not interfere with the infant's immune response to low doses of vaccine. Three 2 micrograms doses of vaccine in infancy produce satisfactory immunogenicity and make possible economic control of hepatitis B in endemic areas. PMID- 2879102 TI - Basic information that prescribers are not getting about drugs. PMID- 2879103 TI - Oral rehydration solution--too little or too much? PMID- 2879104 TI - Eligibility for thrombolytic therapy in acute myocardial infarction. AB - In a district general hospital's coronary care unit (CCU) 197 patients with chest pain were admitted over a 6-month period and in 131 an acute myocardial infarction (AMI) was confirmed. 67 (51%) were eligible for thrombolytic therapy, on criteria laid down for a trial of streptokinase. Criteria for thrombolysis were not fulfilled in 41 (31%) and 12 patients (9%) had contraindications. These results suggest that around half of all patients with AMI and about one-third of patients presenting with chest pain and admitted to a CCU would be suitable for thrombolytic therapy. These data do not support the view that such therapy may be applicable to only a small minority of patients with AMI. PMID- 2879105 TI - Clinical significance of tamoxifen withdrawal response. PMID- 2879106 TI - Goserelin therapy before surgery for uterine fibroids. PMID- 2879107 TI - Failure to provide a sample for breath alcohol analysis. PMID- 2879108 TI - Passive smoking and birthweight. PMID- 2879109 TI - Free radicals, lipid peroxidation, and Parkinson's disease. PMID- 2879110 TI - Parkinson's disease and pesticides. PMID- 2879111 TI - MPTP, selegiline, and parkinsonism. PMID- 2879112 TI - Teicoplanin-resistant coagulase-negative staphylococci. PMID- 2879113 TI - Recombination between Duchenne muscular dystrophy and DNA marker DXS164 (pERT87) PMID- 2879114 TI - Sensitivity and specificity of eight commercial and one recombinant anti-HIV ELISA tests. PMID- 2879115 TI - Inhibition of HIV-induced cytopathogenicity in vitro by 3'-azido-2',3' dideoxyguanosine. PMID- 2879116 TI - Assessment of airflow obstruction. PMID- 2879117 TI - Diuretic abuse and idiopathic oedema. PMID- 2879118 TI - Peritonitis caused by slime-producing coagulase negative staphylococci in continuous ambulatory peritoneal dialysis. PMID- 2879119 TI - Vomiting and the migrating motor complex. PMID- 2879120 TI - Sleep after transmeridian flights. PMID- 2879121 TI - Leukaemic relapse after Campath 1-treated bone-marrow transplantation for leukaemia. PMID- 2879122 TI - 99mTc-HMPAO for labelling leucocytes in infection. PMID- 2879123 TI - Legal interference and clinical freedom. PMID- 2879124 TI - Patients reading their notes. PMID- 2879125 TI - Patients' rights and the Mental Health Act. PMID- 2879126 TI - Parents in the anaesthetic room. PMID- 2879128 TI - Urinary incontinence in elderly patients. PMID- 2879127 TI - Potential side-effects of erythropoietin. PMID- 2879129 TI - Brain death and cerebral blood flow. PMID- 2879130 TI - Cerebral deficit after elective cardiac surgery. PMID- 2879131 TI - Cisapride in postoperative gastroparesis. PMID- 2879132 TI - Fatal liver failure in children on valproate. PMID- 2879133 TI - Akathisia and antipsychotic drugs. PMID- 2879134 TI - Valproate-induced inhibition of urea synthesis. PMID- 2879135 TI - Perinatal infection with cryptosporidium and failure to thrive. PMID- 2879136 TI - When should at-risk infants be boosted with hepatitis B vaccine? PMID- 2879137 TI - Can Doppler ultrasound predict outcome of post-asphyxial encephalopathy? PMID- 2879139 TI - GIFT in a district hospital. PMID- 2879138 TI - Treatment of growth-hormone deficiency with growth-hormone-releasing hormone. AB - 18 prepubertal growth-hormone (GH)-deficient children were treated with twice daily subcutaneous injections of a growth-hormone-releasing hormone analogue, GHRH (1-29) NH2. In 12 of the children the height velocity rose on GHRH treatment, and 8 were judged to have shown a worthwhile response to therapy in that their height velocities during the first 6 months of treatment increased by greater than 2 cm/yr (range 2.7-11.2 cm/yr). These 8 children have now been treated for 6 to 18 months and their increase in height velocity has been maintained. In the 14 patients who had previously received human GH (hGH) height velocity on hGH correlated with that on GHRH. 4 of these patients showed growth deceleration with GHRH, for unknown reasons. A pretreatment peak serum GH response of above 30 mU/l during an intravenous GHRH test was predictive of a good growth response to GHRH but a lower peak did not preclude a growth response. There was no consistent evidence of a priming or desensitisation effect of therapy on the GH responses to GHRH. Although anti-GHRH antibodies developed in 14 patients, these did not seem to have adverse effects on either growth or the GH responses to GHRH. GHRH (1-29) NH2 therapy is an alternative to conventional hGH in the treatment of some GH-deficient children. Ideal dose regimens need to be established. PMID- 2879140 TI - Human parvovirus and rubella cross-reactions in specific IgM tests. PMID- 2879141 TI - Obstetric hysterectomy. PMID- 2879142 TI - Identification of cryptosporidium oocysts by monoclonal antibody. PMID- 2879144 TI - Intrauterine insemination. PMID- 2879143 TI - Pericardial friction rubs in hepatorenal failure. PMID- 2879146 TI - Research on human embryos. PMID- 2879145 TI - Misuse of mefloquine for malaria prophylaxis in Zimbabwe. PMID- 2879147 TI - Antibody titres to a rough-mutant strain of Escherichia coli in patients undergoing allogeneic bone-marrow transplantation. Evidence of a protective effect against graft-versus-host disease. AB - Much clinical and experimental evidence suggests that infection and graft-versus host disease (GvHD) are commonly associated as complications of bone-marrow transplantation (BMT). A likely basis for this association is the gram-negative faecal flora,the origin of many septicaemias and a source of bacterial endotoxin, which has potent immunostimulatory effects. A rough-mutant strain, Escherichia coli J5, has only core determinants in its endotoxin,and antibodies to E coli J5 protect animals and human beings from the consequences of septic shock. Naturally occurring antibodies to E coli J5 ("anti-endotoxin") were assayed in serum from patients undergoing BMT, healthy controls, and patients with obstructive jaundice. BMT recipients had significantly lower titres than the other two groups. Furthermore, the titre of IgM class anti-J5 antibody was significantly associated with protection from GvHD. PMID- 2879148 TI - New focus of Chagas' disease in Mexico. PMID- 2879149 TI - Yellow fever and the traveller. PMID- 2879150 TI - Chloroquine for donated blood? PMID- 2879151 TI - Analgesics, agranulocytosis, and aplastic anaemia. PMID- 2879152 TI - Brain damage after high-altitude climbs without oxygen. PMID- 2879153 TI - Digoxin-like immunoreactive factor and premature labour. PMID- 2879155 TI - Plasma exchange for cerebral lupus erythematosus. PMID- 2879154 TI - Hepatic bile nucleation and gallstone disease. PMID- 2879156 TI - An investigation by the ABPI (Association of the British Pharmaceutical Industry) PMID- 2879157 TI - Confidentiality and pre-employment health screening. PMID- 2879158 TI - Medicine in southern Sudan. PMID- 2879160 TI - Sleep deprivation, dieting, and depression markers. PMID- 2879159 TI - Percutaneous laser angioplasty with sapphire tip. PMID- 2879161 TI - Mother-to-child transmission in HTLV-I associated myelopathy. PMID- 2879162 TI - Non-endoscopic relief of oesophageal obstruction. PMID- 2879163 TI - Computerised tomographic scanning and staging of gastric carcinoma. PMID- 2879164 TI - Epidural clonidine. PMID- 2879165 TI - Abnormalities in children exposed to benzodiazepines in utero. PMID- 2879166 TI - Serum neuron-specific enolase may be raised in children with Wilms' tumour. PMID- 2879167 TI - Overwhelming pneumococcal sepsis in healthy adults years after splenectomy. PMID- 2879168 TI - Ocular cowpox. PMID- 2879169 TI - Gamete intrafallopian transfer in a non-IVF unit. PMID- 2879170 TI - Disappointing results with direct intraperitoneal insemination. PMID- 2879171 TI - Hair root DNA: a source of constitutional DNA in leukaemia. PMID- 2879172 TI - Roussel convicted of misleading promotion. PMID- 2879173 TI - Survival and renal function in untreated hypercalcaemia. Population-based cohort study with 14 years of follow-up. AB - 172 persons with mild to moderate hypercalcaemia were followed up for 14 years. Life-table analyses showed that, among persons aged 70 years or less at the time of detection of the hypercalcaemia, survival was lower in the hypercalcaemic group than in a normocalcaemic age and sex matched control group. No such difference was found among older persons. The lower survival was related to degree of hypercalcaemia, and this held true when systolic and diastolic blood pressure, serum glucose, serum uric acid, and serum cholesterol were taken into account in a multivariate analysis. The lower survival seemed to be due mainly to deaths from diseases of the circulatory organs. No person with normal renal function at the beginning of the study period had a more than marginally raised serum creatinine at follow-up. PMID- 2879174 TI - Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response. AB - In a randomised controlled trial, preterm babies undergoing ligation of a patent ductus arteriosus were given nitrous oxide and d-tubocurarine, with (n = 8) or without (n = 8) the addition of fentanyl (10 micrograms/kg intravenously) to the anaesthetic regimen. Major hormonal responses to surgery, as indicated by changes in plasma adrenaline, noradrenaline, glucagon, aldosterone, corticosterone, 11 deoxycorticosterone, and 11-deoxycortisol levels, in the insulin/glucagon, molar ratio, and in blood glucose, lactate, and pyruvate concentrations were significantly greater in the non-fentanyl than in the fentanyl group. The urinary 3-methylhistidine/creatinine ratios were significantly greater in the non fentanyl group on the second and third postoperative days. Compared with the fentanyl group, the non-fentanyl group had circulatory and metabolic complications postoperatively. The findings indicate that preterm babies mount a substantial stress response to surgery under anaesthesia with nitrous oxide and curare and that prevention of this response by fentanyl anaesthesia may be associated with an improved postoperative outcome. PMID- 2879175 TI - Brain water measured by magnetic resonance imaging. Correlation with direct estimation and changes after mannitol and dexamethasone. AB - Brain water content was measured in tissue samples taken at operation from 19 patients with intrinsic cerebral tumours imaged preoperatively by magnetic resonance. A high correlation (r = 0.94, p less than 0.0001) between white matter water content and the longitudinal relaxation time (T1) enabled water content to be estimated from T1 to within 4%. 11 patients received dexamethasone and improved clinically but their T1, and thus brain water content, was unchanged an average of 6 days later. Intravenous infusion of 20% mannitol in 11 patients significantly reduced T1 in oedematous white matter and tumour within 15 min of administration, and by 30 min the T1 of oedematous white matter had fallen to a mean of 32.4 (SEM 7.1) ms, corresponding to a reduction in water content of 1.4 (0.3)%. PMID- 2879176 TI - Chlamydia trachomatis and reactive arthritis: the missing link. AB - Reactive inflammatory arthritis is a common sequel to sexually acquired non gonococcal genital-tract infection. Approximately 50% of cases are associated with Chlamydia trachomatis infection in the genital tract, although conventional cultures of joint material are sterile. Synovium, synovial-fluid cells, or both, from eight patients with sexually acquired reactive arthritis (SARA) and eight with knee effusions associated with other rheumatic diseases were examined by means of a fluorescein-labelled monoclonal antibody to C trachomatis ('Micro Trak'; Syva). Typical chlamydial elementary bodies were seen in joint material from five patients with SARA but in none of the controls. An inclusion-like cluster of elementary bodies was seen in one synovial biopsy sample. All five patients had high titres of serum chlamydial antibody. It is likely that the synovitis of SARA results directly from the presence of chlamydial elementary bodies in the joint. PMID- 2879177 TI - Common carotid ligation for intracranial aneurysm. PMID- 2879178 TI - Treatment of benzodiazepine dependence. PMID- 2879179 TI - Transdermal antihypertensive drugs. PMID- 2879180 TI - Management of diffuse oesophageal spasm. PMID- 2879181 TI - Beyond the insulin receptor. PMID- 2879182 TI - Research on medical ethics. PMID- 2879183 TI - Is bone-marrow sampling necessary in patients with small-cell lung cancer? PMID- 2879184 TI - Mortality of doctors: do doctors benefit from their medical knowledge? AB - Official population and mortality statistics show that overall mortality of male doctors in Finland in 1971-80 was lower than that of all economically active men. Doctors had lower death rates from cardiovascular disease, tumours, other diseases, causes of death amenable to medical interventions, and accidents and violence, but not suicide. Except for tumours, mortality of male doctors was at the same level or higher than that of men in other professions. Risk of suicide was twice as high for male doctors as for other professions. The numbers of women doctors were too small for firm conclusions about their mortality to be drawn. It is concluded either that doctors do not use their professional knowledge and skills in a way that reduces their own mortality risk or that they are exposed to occupational hazards that cancel out such an effect. Possible hazards are more likely to be mental than physical or chemical. PMID- 2879185 TI - Measures of nutritional status. Survey of young children in north-east Brazil. AB - In 738 children aged under 5 from three communities in north-east Brazil, nutritional status was assessed by four means-weight for age, height for age, weight for height, and middle upper arm circumference (MUAC). As judged by weight for age, 43% of children were adequately nourished and only 2% were severely malnourished. Stunting (less than 85% height for age) was seen in 8% and wasting (less than 70% weight for height) in 1%. There was poor agreement between MUAC (a measure of wasting) and weight for height when the conventional cut-off points for MUAC were applied. Although agreement improved with new MUAC cut-off points the probability of correct diagnosis of wasting (sensitivity) remained low. Although height for age and weight for height were the most useful measures of nutritional status, MUAC may be the best available in famine victims and refugees. PMID- 2879186 TI - Is 24 h ambulatory oesophageal pH monitoring useful in a district general hospital? AB - 53 of 61 patients successfully completed 24 h ambulatory monitoring of oesophageal pH. The indications were: symptoms suggestive of gastro-oesophageal reflux but with normal endoscopy (19 cases); atypical chest pain with normal endoscopy (21 cases); or respiratory symptoms possibly due to reflux (13 cases). A temporal association between abnormal reflux and the presenting symptoms was demonstrated in 25 patients (47%). 6 patients were shown to have respiratory symptoms after episodes of reflux which resolved on treatment of the reflux alone. Reflux occurring only in the erect posture was observed in some patients and may have been a manifestation of the irritable bowel syndrome. Reflux as a cause of symptoms was excluded in 14 patients. The procedure was well tolerated in most patients, simple to operate, and inexpensive. PMID- 2879187 TI - How reliable are commercial allergy tests? AB - The ability to diagnose allergic disease was studied in 9 fish-allergic and 9 control subjects, who provided specimens of blood and hair for testing. All fish allergic subjects had previously been shown at Guy's Hospital to have a positive skin prick test to fish. The specimens were submitted as coded, duplicate samples to five laboratories which all offer a commercial service in carrying out diagnostic tests for allergy. All five laboratories were not only unable to diagnose fish allergy but also reported many allergies in apparently non-allergic subjects and provided inconsistent results on duplicate samples from the same subject. PMID- 2879188 TI - Is there a carrier state in pertussis? PMID- 2879189 TI - One-stage replacement of pacemaker generators. PMID- 2879190 TI - Citrate and salivary drug measurement. PMID- 2879191 TI - Treatment of malignant endocrine pancreatic tumours with human leucocyte interferon. PMID- 2879192 TI - Bovine reservoir for verotoxin-producing Escherichia coli O157:H7. PMID- 2879193 TI - Significance of group B streptococci (Strep agalactiae) in children's urinary tract infection. PMID- 2879194 TI - Broad-complex tachycardia after intravenous cimetidine. PMID- 2879195 TI - [Radiation hazards]. PMID- 2879196 TI - [Computerized tomography in pneumologic evaluation]. PMID- 2879197 TI - [Assessment of prognosis in pulmonary sarcoidosis]. PMID- 2879198 TI - [Insurability of hemophilia patients]. PMID- 2879199 TI - [Therapeutic successes and prognostic criteria in acute leukemia]. PMID- 2879200 TI - [Prognosis of disease conditions in intensive care in internal medicine]. PMID- 2879201 TI - [A new cement-free hip endoprosthesis which can be fitted to the pertrochanteric bone marrow space]. PMID- 2879202 TI - In vitro receptor specificity of the 5HT1A selective phenylpiperazine, LY165163. AB - LY165163, a ligand reported to be selective for the 5HT1A subtype of serotonin receptor, was examined for its ability to interact with 5HT2 receptors in the rat jugular vein and alpha-receptors in the rat aorta. In these smooth muscle preparations, no agonist activity of LY165163 occurred in concentrations up to 10(-5) M. However, LY165163 was an antagonist of serotonin-induced contractions in the jugular vein and of norepinephrine-induced contractions in the rat aorta. The dissociation constant calculated for LY165163 at 5HT2 receptors in the rat jugular vein was 10(-8) M and at alpha-receptors in the rat aorta was 2 X 10(-7) M. Thus, LY165163 is a relatively potent antagonist at vascular 5HT2 sites and possesses appreciable affinity at alpha-receptors. Based on these data, the multiple receptor interactions of LY165163 must be taken into consideration when utilizing this agent as a probe for the 5HT1A subtype of serotonin receptor. PMID- 2879203 TI - 2-Amino-7-phosphonoheptanoic acid (AP7) produces discriminative stimuli and anticonflict effects similar to diazepam. AB - The N-methyl-D-aspartate (NMDA) receptor antagonist, AP7, was evaluated in two animal test procedures known to be sensitive to the effects of diazepam. In rats trained to discriminate diazepam from vehicle, AP7 produced dose-dependent generalization to the diazepam interoceptive stimuli. This NMDA antagonist also increased the rates of conflict responding in a chronic test procedure used to identify compounds with potential anxiolytic effects. A comparison of AP7 with diazepam and two muscle relaxants (methocarbamol and baclofen) showed that excitatory amino acid antagonists (of the receptor site stimulated by NMDA) produce a muscle relaxant effect (drug discrimination) and may represent a new class of compounds for the treatment of anxiety-related disorders (conflict test). PMID- 2879204 TI - In vivo potencies of antipsychotic drugs in blocking alpha 1 noradrenergic and dopamine D2 receptors: implications for drug mechanisms of action. AB - In addition to being dopamine antagonists, all antipsychotic drugs are potent antagonists of alpha-1 noradrenergic receptors. Nevertheless, the contribution of alpha blockade to the clinical therapeutic effects of the antipsychotic drugs has never attracted extensive study. In particular, the relative alpha-1 noradrenergic antagonist potency of antipsychotic drugs has rarely been determined in vivo during extended treatment, although such treatment would provide a better model of clinical drug effects than the determination of potencies in in vitro systems, such as assays of competition for binding sites in tissue homogenates, as is most often done. To estimate the physiological efficacy of antipsychotic drugs as dopamine and alpha adrenergic antagonists, we treated rats for four weeks with daily IP injections of the following antipsychotic drugs: Fluphenazine, 1 mg/kg; haloperidol, 1 mg/kg; chlorpromazine, 25 mg/kg; thioridazine, 25 mg/kg; and clozapine, 25 mg/kg. Effective antagonism should lead to an increase in density of the relevant receptors. After two drug-free days, rats were sacrificed and the affinity and density of dopamine D2 and alpha-1 noradrenergic receptors were determined in striatum and brain exclusive of striatum, respectively. Alpha 1 noradrenergic receptor density but not dopamine receptor density was increased after all treatments. Thus, preliminary experiments with this in vivo model suggest that all antipsychotic drugs are effective antagonists at alpha 1 noradrenergic receptors, while not all are effective antagonists at dopamine D2 receptors. PMID- 2879205 TI - The brain is protected from nutrient excess. AB - Except for L-DOPA, treatment of patients with large doses of neurotransmitter precursors has not provided acceptable therapy for neurologic or psychiatric disorders. Indeed, neurophysiological effects generally have not followed changes in brain concentrations of the precursors or their products. A major reason for this ineffectiveness of precursor-loading may involve the very high metabolic activity of cerebrovascular endothelial cells, which can metabolize the precursor or its products before these reach the brain parenchyma. It is also noteworthy that studies purporting to examine the transport of precursors across the "blood brain barrier" actually may not measure transport as such but rather the disappearance of precursor from the blood. The metabolic effects of the endothelial cell barrier itself would have greatly influence such studies and, heretofore, have been ignored. Thus, transport indices calculated from such experiments may need re-evaluation. Even when nutrients (precursors) are present in the blood in such excess that they do traverse the endothelial "blood-brain barrier" and enter the brain's interstitial space, other mechanisms (e.g., intraneuronal degradation) likely prevent these substances from exerting neurophysiological effects. PMID- 2879206 TI - Discriminative stimulus properties of oxazepam in the pigeon. AB - Five pigeons were trained to discriminate IM injections of oxazepam (4.0 mg/kg) from vehicle with responding maintained under a fixed-ratio 30 schedule of food delivery. Under test conditions, responding increased in a dose-dependent manner in all pigeons after the administration of other benzodiazepines including diazepam (0.01-1.0 mg/kg), temazepam (0.01-3.0 mg/kg), halazepam (0.1-56.0 mg/kg), and midazolam (0.1-1.0 mg/kg) as well as the barbiturate pentobarbital (2.0-8.0 mg/kg) and the non-benzodiazepine anxiolytic CL 218,872 (1.0-8.0 mg/kg). At the higher doses of each of these compounds, over 80% of responding occurred on the oxazepam-appropriate key. Cocaine (0.5-4.0 mg/kg), bupropion (3.0-56.0 mg/kg) and nortriptyline (3.0-56.0 mg/kg) failed to substitute for oxazepam even at doses that decreased rates of responding. The discriminative stimulus (DS) effects of the lowest doses of oxazepam and CL 218,872 that produced 100% drug appropriate responding were blocked by the benzodiazepine antagonist Ro 15-1788. This antagonism was reversed by increasing the dose of the agonists. The DS effects of diazepam were antagonized partially by Ro 15-1788 (3 of 5 pigeons), and the antagonism was reversed by higher doses of diazepam in two of these pigeons. The DS effects of pentobarbital were antagonized by Ro 15-1788 in 2 of 5 pigeons, but the blockade was not reversed by higher pentobarbital doses. PMID- 2879207 TI - Effect of clofibric acid on the molecular species composition of diacyl glycerophosphocholine of rat liver microsomes. AB - The effect of administering p-chlorophenoxyisobutyric (clofibric) acid to rats on the molecular species composition of diacyl-glycerophosphocholine (GPC) of rat liver microsomes was studied. Microsomal choline glycerophospholipids were converted to 1,2-diradyl-3-acetylglycerol and were separated into molecular species by reverse-phase high performance liquid chromatography. Diacyl-GPC consisted of 17 different molecular species. The predominant species were arachidonoyl derivatives, such as 18:0-20:4 (22.2% of the total) and 16:0-20:4 (22.0%). Administration of clofibric acid to rats caused a marked increase in 16:0-18:1 species of diacyl-GPC from 8% to 30%, making these the predominant species of diacyl-GPC in clofibric acid-fed rats. Also, a significant decrease (50% of controls) in 18:0-18:2 and 18:0-20:4 species was observed, whereas the decrease in molecular species containing 16:0 at the 1-position such as 16:0-18:2 and 16:0-20:4 was small (approximately 85% of control). The results show that clofibric acid caused marked changes in the molecular species composition of diacyl-GPC. The participation of 1-acyl-GPC acyltransferase and stearoyl-CoA desaturase in the regulation of the molecular species composition of diacyl-GPC is discussed. PMID- 2879208 TI - Effects of dietary linolenate on the fatty acid composition of brain lipids in rats. AB - Weanling male rats were fed hydrogenated coconut oil to induce essential fatty acid (EFA) deficiency. After 15 weeks, the rats were divided into six groups. Five groups were fed graded amounts of purified linolenate (18:3 omega 3) with a constant amount of linoleate (18:2 omega 6) for six weeks. Fatty acid composition was determined in brain lipids. Increasing dietary 18:3 omega 3 resulted in a decrease in arachidonic acid (20:4 omega 6), docosatetraenoic acid (22:4 omega 6) and docosapentaenoic acid (22:5 omega 6), whereas 18:2 omega 6 and eicosatrienoic acid (20:3 omega 6) were increased both in total lipids and phospholipids. These results suggest that dietary 18:3 omega 3 exerts its inhibitory effect mainly on the desaturation of 20:3 omega 6 to 20:4 omega 6 in brain lipids. Linolenate was undetectable in brain lipids from any dietary treatments. The levels of eicosapentaenoic acid (20:5 omega 3) in groups receiving dietary 18:3 omega 3 were not different from that of the group receiving no 18:3 omega 3. These results indicate that, in the brain, 18:3 omega 3 is rapidly converted mainly to 22:6 omega 3 without being accumulated and imply that dietary 18:3 omega 3 can modulate the level of precursor of diene prostaglandins (PG) but not that of triene PG in the rat brain. PMID- 2879209 TI - The influence of progressive hyperinsulinemia on duodenal calcium absorption in the rat. AB - Using an in situ loop technique, we studied the influence of moderate hyperinsulinemia on the bidirectional fluxes [lumen-to-plasma (LP), plasma-to lumen (PL)] and on the net absorption of calcium (Ca) in the duodenum of the rat. Under hyperinsulinemic euglycemic clamp conditions, three different steady-state plasma insulin levels (66 +/- 16, 187 +/- 13, 263 +/- 24 microU/mL) were maintained by intravenous (IV) infusion of either 20, 40, or 60 mU/h of insulin. LP flux and net Ca absorption (CaA) increased significantly under all, while the PL flux was not changed by any of the three insulin doses. Under 40 and 60 mU/h of IV insulin, the individual plasma insulin levels and LP fluxes were positively and significantly correlated, suggesting a dose-dependent action of insulin on duodenal CaA. No significant changes were seen in plasma somatostatinlike immunoreactivity (SLI), parathyroid hormone (PTH), and serum Ca, while serum inorganic phosphate (Pi) and 1,25(OH)2 vitamin D levels fell with increasing doses of IV insulin. It is concluded for the rat that physiologic degrees of hyperinsulinemia enhance duodenal CaA by an as yet unknown mechanism, this action seems to be independent of PTH and, the role of 1,25(OH)2 vitamin D in this context is poorly understood. PMID- 2879210 TI - Changes in plasma growth hormone in diabetic and nondiabetic subjects during the glucose clamp. AB - A group of 22 newly diagnosed noninsulin-dependent diabetic subjects and seven nondiabetic subjects underwent a glucose clamp at plasma glucose 100 mg/dL with insulin infusion rates of 1.0 and 10 mU/kg/min. During both insulin infusion rates, there was a sustained rise in plasma growth hormone (GH) above basal in 18 of the 22 diabetic subjects. Basal GH values were 2.37 +/- 0.67 ng/mL, rising above basal during the lower insulin infusion (6.1 +/- 3.3 ng/mL, P = 0.05) with a further rise at the higher insulin level (8.58 +/- 2.0 ng/mL, P less than 0.001). There was no rise in GH in any of the nondiabetic subjects. In neither group was there any rise above basal in cortisol, prolactin, glucagon, or somatostatin (SRIH). In a group of three nondiabetic subjects, a rise in GH similar to that seen in the diabetic group was induced by elevating the plasma glucose to 200 mg/dL for 60 minutes prior to the euglycemic clamp procedure. However, it is unlikely that changes in plasma glucose account totally for the changes in plasma GH described in the diabetic subjects since a rise in plasma GH was also seen in four diabetic subjects clamped at their fasting plasma glucose. We conclude that in newly diagnosed noninsulin-dependent diabetic subjects there is a rise in plasma GH during the euglycemic clamp procedure, which may be due to both the prior lowering of plasma glucose and the high plasma insulin levels. PMID- 2879211 TI - Reverse tri-iodothyronine as part of alpha 2 adrenergic receptors. AB - Thyroid hormones affect alpha and beta adrenergic receptor number profoundly. Presynaptic and post synaptic alpha 2 adrenergic receptor number is decreased in hypothyroidism. Behavioural studies show decreased presynaptic alpha 2 adrenergic function in hypothyroidism and increased function in hyperthyroidism. Reverse tri iodothyronine (rT3) levels are also low in hypothyroidism and levels are high in hyperthyroidism induced by T4 administration. The present author has proposed that rT3 is incorporated into the alpha 2 adrenergic receptor where it provides the aromatic binding site. Tri-iodothyronine (T3) administration does not raise alpha 2 adrenergic receptor numbers above normal control values. This is consistent with the author's hypothesis as T3 cannot be converted to rT3. This paper describes how rT3 could provide the aromatic binding site for drugs that act on alpha 2 adrenergic receptors. PMID- 2879212 TI - The vitamin C treatment of allergy and the normally unprimed state of antibodies. AB - I previously described that bowel tolerance (the amount that almost causes diarrhea) to oral ascorbic acid, increases in a person somewhat proportionally to the "toxicity" of his disease. Ascorbic acid ameliorates symptoms and sometimes cures certain diseases at high threshold levels near bowel tolerance. High concentrations of ascorbate cause the redox potential of the redox couple (ascorbate/dehydroascorbate, AA/DHA) to become reducing in diseased tissues. Allergic and sensitivity reactions are frequently ameliorated and sometimes completely blocked by massive doses of ascorbate. I now hypothesize that one mechanism in blocking of allergic symptoms is the reducing of the disulfide bonds between the chains in antibody molecules making their bonding antigen impossible. I further hypothesize that antibodies seek to match antigens only in areas where stray free radicals or a relatively oxidizing redox potential exists. The redox state of normal, healthy tissue does not allow for the bonding of antibodies to antigen. When antioxidant, free radical scavenging systems are overwhelmed, inflammatory, hypersensitivity, and "autoimmune" conditions may result. PMID- 2879213 TI - Further understanding of, and a new treatment for, "Irukandji" (Carukia barnesi) stings. AB - A brief analysis is presented of the large recorded numbers of swimmers who have been stung by the "Irukandji" (Carukia barnesi) jellyfish during the 1985-1986 summer season in north Queensland, and the results are discussed. Many of the victims may suffer from symptoms of overstimulation of the sympathetic system, and hypertension is shown to be another complication of this syndrome. This hypertension seems to respond well to intravenously-administered phentolamine, an alpha-adrenergic receptor blocking drug. Phentolamine also reduces the excessive shaking and sweating that appears to be part of the "Irukandji syndrome". Diazepam relieves the anxiety which is part of the syndrome, but antihistamine agents and hydrocortisone seem to have no beneficial effect. PMID- 2879214 TI - Treatment of benzodiazepine dependence. PMID- 2879216 TI - [Neurohormonal relations between brain and gastrointestinal tract]. PMID- 2879215 TI - Medical reality and political deceptions. PMID- 2879218 TI - [Dentomaxillofacial traumatology in the game of squash]. PMID- 2879217 TI - [Frequently used beta-blockers and circulating thyroid hormones]. PMID- 2879219 TI - [Role of blood flow in acute gastric lesion after hepatectomy and effect of prostaglandin I2 and H2-receptor antagonist]. AB - In order to investigate the cause of gastric mucosal lesion following hepatectomy, changes of gastric, pancreatic and femoral arterial blood flow were measured in 70% hepatectomized rabbits. Following administration of 0.5 microgram/kg of GRP, gastric blood flow increased to 120% of the basal level in the controls, but reached to only 107% of the basal level in the hepatectomized rabbits. Following hemorrhage of 10% of the total blood volume seven days after hepatectomy, blood flow decreased to 55% of the basal level in the stomach, 57% in the pancreas and 76% in the femoral artery. Although pancreatic blood flow recovered to 81% of the basal level, gastric blood flow remained low, 59% of the basal level, suggesting poor recovery of gastric blood flow as compared to pancreatic blood flow. Administration of PGI2 and ranitidine in hepatectomized rabbits with hemorrhage conferred a considerable degree of recovery of gastric blood flow in the PGI2 group (from 56% to 80%) and in the ranitidine group (from 52% to 72%). Thus, disturbance of reaction and poor recovery of gastric blood flow following hemorrhage were indicated as important causes of acute gastric mucosal lesion associated with hepatectomy. Both PGI2 and ranitidine appeared to be effective for the maintenance of gastric blood flow after hepatectomy. PMID- 2879220 TI - [Effect of propranolol on intractable ascites following liver resection]. AB - Hepatic and respiratory failure, common complications following liver resection for hepatocellular carcinoma (HCC), especially when it is combined with liver cirrhosis, can be overcome by careful management of the circulatory and respiratory systems. Another common complication is intractable ascites which resists conventional therapy, such as, diuretics and protein replacement. Here we report a case in which intractable ascites was successfully treated with propranolol. The patient, a 48-year-old man who underwent liver resection for HCC combined with cirrhosis, started to suffer from ascites about 1 week after surgery. Upon administration of propranolol (1 mg/kg/day) with furosemide, his body weight decreased 500 g/day, returning to the preoperative value in 2 weeks in parallel with the normalization of the PRA. No side effects were observed during the medication period. Propranolol, a beta-adrenergic antagonist, is thought to suppress renin secretion from the juxtaglomerular apparatus in the kidney by blocking its beta-adrenergic receptor, thus suppressing the entire renin-angiotensin-aldosterone system. We concluded that propranolol is a promising drug for intractable ascites encountered with liver cirrhosis. PMID- 2879221 TI - Fine-structure analysis of the processing and polyadenylation region of the herpes simplex virus type 1 thymidine kinase gene by using linker scanning, internal deletion, and insertion mutations. AB - Most eucaryotic mRNAs are polyadenylated. In higher eucaryotes, the sequence AATAAA is located 7 to 30 base pairs (bp) upstream from the site of processing and polyadenylation and is a critical part of the signal for processing and polyadenylation. Efficient cleavage and polyadenylation also require sequences downstream of polyadenylation sites. The herpes simplex virus type 1 thymidine kinase (tk) gene contains two copies of the AATAAA hexanucleotide and a GT box (18 of 19 consecutive residues are G or T) previously shown to be required for efficient processing and polyadenylation of tk mRNA (C. N. Cole and T. P. Stacy, Mol. Cell. Biol., 5:2104-2113). To define further the sequence requirements for efficient polyadenylation, we prepared linker scanning, internal deletion, and small insertion mutations in the polyadenylation region of the tk gene. These mutations were analyzed by S1 nuclease protection analysis of cytoplasmic RNA isolated from transfected Cos-1 monkey kidney cells. When the proximal AATAAA was deleted, no tk mRNA polyadenylated in the normal region was detected, whereas replacement of the second AATAAA with an XbaI linker had no effect on polyadenylation. When various portions of the GT box were replaced with linker, the amount of tk mRNA produced was reduced to 23 to 82% of the normal amount, but polyadenylation in the normal region was never abolished. Thus, no single portion of the GT box was absolutely required. In some cases, extended transcripts, polyadenylated at a cryptic site within pBR322, were detected. A spacing of 6 bp between AATAAA and the GT box was too short for efficient processing and polyadenylation. A spacing of 30 bp appeared to work almost as efficiently as did the wild-type spacing of 18 bp. Taken together, these results indicate that efficient polyadenylation requires both AATAAA and downstream GT-rich sequences. In addition, processing and polyadenylation are affected both qualitatively and quantitatively by sequences at polyadenylation sites and at more distant locations. PMID- 2879222 TI - Multiple transcripts from the Antennapedia gene of Drosophila melanogaster. AB - The structures of four major transcripts from the homeotic gene Antennapedia of Drosophila melanogaster were determined. These transcripts constitute two RNA classes, each class initiating from a unique promoter but sharing 3' exons. Within the shared sequences is a major open reading frame encoding a 378-amino acid protein as well as alternative polyadenylation sites. Although the RNA classes differ in their 5' sequences, both leaders contain many AUGs upstream of the major open reading frame. For the two RNA classes, neither gross tissue nor temporal specificity was observed. However, the second poly(A) site is preferred in neural tissue. The structural diversity of the RNAs is discussed in relation to biological functions of the Antennapedia locus. PMID- 2879223 TI - Structure of transcripts from the homeotic Antennapedia gene of Drosophila melanogaster: two promoters control the major protein-coding region. AB - The Antennapedia (Antp) homeotic gene of Drosophila melanogaster regulates segmental identity in the thorax. Loss of Antp function results in altered development of the embryonic thoracic segments or can cause legs to be transformed into antennae. Certain combinations of Antp recessive lethal alleles complement to permit normal development. The structure of the Antp gene, analyzed by sequencing cDNA clones and exons and by transcript mapping, revealed some of the basis for its genetic complexity. It has two promoters governing two nested transcription units, one unit 36 and one 103 kilobase pairs (kb) long. Both units incorporated the same protein-coding exons, all of which are located in the 3' most 13 kb of the gene. The two promoters resulted in the attachment of either of two long noncoding leader sequences (1.5 and 1.7 kb) to a 1.1-kb open reading frame. Both transcription units used the same pair of alternative polyadenylation sites 1.4 kb apart; the choice of sites was developmentally regulated. Some of the mutations that disrupt the larger transcription unit complemented a mutation affecting the smaller one. Dominant mutations that transform antennae into legs split the gene but left the coding exons intact. The encoded protein has unusually long runs of glutamine and a homeodomain near the C terminus. PMID- 2879224 TI - Differential amplification and disproportionate expression of five genes in three multidrug-resistant Chinese hamster lung cell lines. AB - At least five linked genes are amplified in the multidrug-resistant Chinese hamster ovary cell line CHRC5, selected with colchicine (A. M. Van der Bliek, T. Van der Velde-Koerts, V. Ling, and P. Borst, Mol. Cell. Biol. 6:1671-1678, 1986). We report here that only a subset of these, encoding the 170-kilodalton P glycoprotein, are consistently amplified in three different multidrug-resistant Chinese hamster lung cell lines, selected with vincristine, daunorubicin, or actinomycin D. Within each cell line, genomic sequences homologous to the P glycoprotein cDNA probe were amplified to different levels. The pattern of differential amplification was consistent with the presence of at least two and possibly three P-glycoprotein genes. In the actinomycin D-selected cell line, these genes were disproportionately overexpressed relative to the associated levels of amplification. These results underline a central role for P glycoprotein in multidrug resistance. In the daunorubicin-selected cell line, another, as yet uncharacterized, gene was amplified but disproportionately underexpressed. Its amplification was therefore fortuitous. We present a tentative map of the region in the hamster genome that is amplified in the multidrug-resistant cell lines which were analyzed. PMID- 2879226 TI - [Carnitine in the treatment of methylmalonic aciduria (MMA)]. AB - Carnitine metabolism was studied and a therapeutic trial with L-carnitine was undertaken in 3 patients with methylmalonic aciduria. Prior to carnitine therapy, the concentration of free carnitine was diminished and the contribution of acylated carnitine to total carnitine was increased in both plasma and urine. During a metabolic crisis, in a patient the intravenous administration of L carnitine greatly increased, the urinary excretion of acylcarnitine and the plasma concentration of methylmalonic acid fell. In all 3 patients, the chronic oral administration of L-carnitine resulted in the normalisation of the plasma free carnitine concentrations and an increased urinary excretion of carnitine esters. One patient clearly showed clinical improvement under carnitine therapy. The administration of L-carnitine to patients with methylmalonic aciduria results in an increased elimination of toxic propionyl groups and thus to a regeneration of intramitochondrial CoA. In conjunction with appropriate dietary measures, this may improve the metabolic situation of these patients. PMID- 2879227 TI - Systemic hormones, neurotransmitters and brain development. International symposium. Berlin, September 12-14, 1985. PMID- 2879225 TI - A novel RNA in which the 5' end is generated by cleavage at the poly(A) site of immunoglobulin heavy-chain secreted mRNA. AB - We describe processed RNA species generated by cleavage at poly(A) sites in the immunoglobulin mu and gamma 2b heavy-chain transcription units. These "amputated transcripts" began at the first or "secreted" poly(A) site and ended at the second or "membrane" poly(A) site. Although they were polyadenylated and apparently spliced, they were largely restricted to the nucleus. Their existence confirms that the heavy-chain mRNAs are derived from RNA cleavage at alternative poly(A) sites. PMID- 2879228 TI - The development of prolactin, growth hormone, alpha-melanocyte-stimulating hormone and monoaminergic systems in the rat. PMID- 2879229 TI - Hormone-dependent brain development and preventive medicine. PMID- 2879230 TI - Environment-dependent changes of neurotransmitter levels in the developing brain of rats. PMID- 2879231 TI - [Dental soldering. VI. Fitness accuracy of the soldering method with electrical tacking]. PMID- 2879232 TI - [Purification and various properties of pyroglutamyl peptidase from Rothia dentocariosa]. PMID- 2879233 TI - [Physical map of Pseudomonas aeruginosa phage phi kF77 genome. Localization of sites sensitive to restriction endonucleases]. AB - A physical map of the P. aeruginosa bacteriophage phi kF77 has been constructed using the restriction endonucleases SalI, HindIII, EcoRI, EcoRV, MuI, XbaI, ClaI. The phi kF77 DNA is resistant to cleavage by the restriction endonucleases BamHI, BglII, HpaI, PstI, PvuII, SmaI, XhoI. PMID- 2879234 TI - [Characteristics of inheritance of restriction fragment polymorphisms for non transcribed spacers of human rRNA genes]. AB - Inheritance of polymorphous restricts of nontranscribed spacer (NTS) located to the right from 3'-end of 28S rRNA gene has been studied in families. Single classes of NTS polymorphous fragments are presented in the genome by some tenths of copies and are inherited as a simple mendelian characteristic located on separate chromosomes. PMID- 2879235 TI - Short-term management of nesidioblastosis using the somatostatin analogue SMS 201 995. PMID- 2879236 TI - Long-term treatment of an infant with nesidioblastosis using a somatostatin analogue. PMID- 2879237 TI - Brain neurotransmitters in dystonia. PMID- 2879238 TI - The SA Society of Radiation Therapists. Notes on the 10th National Congress. PMID- 2879240 TI - Anatomical and biochemical perspectives on opioid peptides. PMID- 2879239 TI - Dynorphin: specific binding to opiate receptors. PMID- 2879241 TI - New data from mammalian homoeobox-containing genes. PMID- 2879242 TI - The c-erb-A protein is a high-affinity receptor for thyroid hormone. AB - Hormone binding and localization of the c-erb-A protein suggest that it is a receptor for thyroid hormone, a nuclear protein that binds to DNA and activates transcription. In contrast, the product of the viral oncogene v-erb-A is defective in binding the hormone but is still located in the nucleus. PMID- 2879243 TI - The c-erb-A gene encodes a thyroid hormone receptor. AB - The cDNA sequence of human c-erb-A, the cellular counterpart of the viral oncogene v-erb-A, indicates that the protein encoded by the gene is related to the steroid hormone receptors. Binding studies with the protein show it to be a receptor for thyroid hormones. PMID- 2879244 TI - Homoeobox gene expression in mouse embryos varies with position by the primitive streak stage. AB - Pattern formation in animal development requires that genes be expressed differentially according to position in the sheets of cells that make up the early embryo. The homoeobox-containing genes of Drosophila are control genes active both in the establishment of a segmentation pattern and in the specification of segment identity. In situ hybridization experiments confirm that these genes are expressed in a segmentally-restricted manner and that their expression presages morphological differentiation of segmental structures. Homoeobox genes have recently been isolated from the mouse and have been shown to be expressed during mouse development. Using in situ hybridization, we show here that expression of the mouse homoeobox gene Mo-10 (ref. 7) is spatially restricted in the developing embryo and that localization of expression is already evident within the germ layers before their morphological differentiation. These findings support the suggestion that the homoeobox genes of mammals, like those of Drosophila, may be important in pattern formation. PMID- 2879245 TI - Differential and stage-related expression in embryonic tissues of a new human homoeobox gene. AB - The homoeobox is a 183 base-pair (bp) DNA sequence conserved in several Drosophila genes controlling segmentation and segment identity. Homoeobox sequences have been detected in the genome of species ranging from insects and anellids to vertebrates and homoeobox containing genes have been cloned from Xenopus, mouse and man. We recently isolated human homoeobox containing complementary DNA clones, that represent transcripts from four different human genes. One clone (HHO.c10) is selectively expressed in a 2.1 kilobase (kb) polyadenylated transcript in the spinal cord of human embryos and fetuses 5-10 weeks after fertilization. We report the characterization of a second cDNA clone, termed HHO.c13, that represents a new homoeobox gene. This clone encodes a protein of 255 amino-acid residues, which includes a pentapeptide, upstream of the homoeo domain, conserved in other Drosophila, Xenopus, murine and human homoeobox genes. By Northern analysis HHO.c13 detects multiple embryonic transcripts, which are differentially expressed in spinal cord, brain, backbone rudiments, limb buds and heart in 5-9-week-old human embryos and fetuses, in a striking organ- and stage-specific pattern. These observations suggest that in early mammalian development homoeobox genes may exert a wide spectrum of control functions in a variety of organs and body parts, in addition to the spinal cord. PMID- 2879247 TI - Nomenclature for homoeobox-containing genes. PMID- 2879246 TI - In vivo protein-DNA interactions in a glucocorticoid response element require the presence of the hormone. AB - Transcriptional activation of gene expression by glucocorticoid hormones is mediated by the interaction of hormone-receptor complexes with specific DNA sequences called glucocorticoid responsive elements (GREs) (refs 1-3, see ref. 4 for review). Deletion of this sequence abolishes glucocorticoid induction of transcription. According to a current model, activation of the cytoplasmic receptor protein by hormone binding leads to its increased affinity for and translocation to the nucleus. However, recent reports that the oestradiol and progesterone receptors are localized in the nucleus in the absence of steroid led us to examine whether the free receptor interacts in vivo with its DNA binding site in the absence of hormone binding. We used the genomic footprinting technique to show that changes in in vivo protein-DNA interactions within the GREs of the tyrosine aminotransferase gene (TAT) can be detected only after hormone treatment in hepatoma cells. Such changes are not detected in fibroblast cells, in which the TAT gene is not expressed. Many of the changes in dimethylsulphate reactivity observed in the living cell are also found in vitro using cloned DNA and a partially purified glucocorticoid receptor. PMID- 2879248 TI - Activation of a calcium-dependent photoprotein by chemical signalling through gap junctions. AB - In the hydrozoan coelenterate Obelia geniculata, epithelial cell action potentials trigger light emission from photocyte effector cells containing obelin, an endogenous calcium-activated photoprotein. As this luminescence is blocked by the removal of extracellular calcium it seemed likely that calcium entry via voltage-gated channels in the photocyte membrane would account for the light emission. However, no inward calcium current was detected in whole cell recordings from dissociated photocytes and depolarization of isolated photocytes produced no luminescence. In contrast, a voltage-dependent calcium current was recorded from non-luminescent support cells, and activation of this current triggered luminescence in an adjacent photocyte. Surprisingly, light emission was abolished when the gap junctions between the photocyte and support cell were blocked. We conclude that calcium entry into support cells leads to light emission from neighbouring photocytes via chemical signalling through intercellular gap junctions. PMID- 2879249 TI - Evidence against Ha-ras-1 involvement in sporadic and familial melanoma. AB - It was recently reported that different rare alleles at the Ha-ras-1 locus occurred at a significantly higher combined frequency in cancer patients than in an unaffected population. In particular, melanoma patients were reported to have a significantly higher frequency of such alleles. We have examined the frequency of rare Ha-ras-1 alleles in a large number of cases of sporadic melanoma. Our results indicate that the distribution of rare alleles in this population does not differ from that found in normal populations. Also, to test the hypothesis that a hereditary predisposition to melanoma could be inherited via an allele at the Ha-ras-1 locus, we examined the transmission of the segment of the short arm of chromosome 11 (11p) carrying the Ha-ras-1 locus in a number of families previously shown to exhibit a hereditary predisposition to melanoma and its precursor lesion, the dysplastic nevus syndrome (DNS). Our genetic linkage results thus obtained strongly exclude the association of a predisposition to melanoma or the precursor lesion with the inheritance of the Ha-ras-1 locus or the segment of chromosome 11 on which it is located. These results imply that hereditary predisposition to melanoma is associated with genes other than the Ha ras-1 locus, contradicting the original suggestion of Krontiris et al., made on the basis of either an inadequate sample size or other misleading experimental factors. PMID- 2879250 TI - Autotransfusion in bilateral internal mammary artery bypass: cost effectiveness in the 1980s. PMID- 2879251 TI - LAV/HTLV-III and HTLV-I antibodies in hemodialysis patients. PMID- 2879252 TI - [Hemorrhagic fever with renal syndrome. Apropos of 13 cases observed in Lorraine]. AB - Thirteen cases of hemorrhagic fever with renal syndrome (HFRS) have been observed in the Nancy area. Ten occurred during the summer of 1983 and three in April and May 1985. The clinical characteristics were in each case very typical: abrupt onset with high fever, myalgia, intense lumbar and abdominal pain, pulsatile headache, inflammatory syndrome, WBC count increase and thrombocytopenia. Acute renal failure occurred a few days later with oliguria (9 cases out of 13), massive proteinuria (9/13) and hematuria (6/13). All patients recovered without sequelae within 8-10 days. Renal biopsy performed in 8 patients showed slight tubular lesions with interstitial mononuclear cell infiltrate, congestion and diffuse interstitial edema, and in 2 cases hemorrhagic extravasation. No glomerular lesions were observed. Clinical, histological and epidemiological characteristics of these 13 French cases are highly similar to those of the Scandinavian Nephropathia Epidemica reports. The epidemiology of HFRS remains unclear as do its pathophysiological mechanisms. PMID- 2879253 TI - The anterior periventricular hypothalamus is the site of somatostatin inhibition of its own release: an in vitro and immunocytochemical study. AB - The site of action of the inhibitory effect of somatostatin (SRIF) on its own release was studied by: (1) measuring SRIF release in vitro from tissue preparations containing either the proximal (periventricular hypothalamus) or the distal (median eminence) portions of the hypothalamic SRIF neurons, and (2) immunocytochemical investigation of the interconnections occurring between SRIF neuronal elements in these hypothalamic regions. In vitro, a biologically active, but noncross-reacting SRIF analog (D-Trp8 SRIF) in the RIA, inhibited 25 mM K+ induced SRIF release from anterior periventricular hypothalamic tissues. The inhibitory effect of D-Trp8 SRIF was dose-dependent, maximal at 10(-7) M, and restricted to this anterior region, since median-eminence SRIF release was not modified by the presence of D-Trp8 SRIF. Additionally, LHRH release from anterior periventricular hypothalamus was unchanged in the presence of D-Trp8 SRIF. In the periventricular nucleus, perikarya and dendrites of labeled SRIF neurons showed frequent apposition of their limiting membranes. Classical synapses were also observed between SRIF-containing axonal processes and labeled perikarya or dendrites. Although membrane appositions between neighboring SRIF axons frequently occurred in the median eminence, no synaptic-like SRIF-SRIF connections could be detected at this level. The data demonstrate a direct inhibitory action of a SRIF agonist on the anterior periventricular hypothalamic release of the peptide. This effect correlates well with the occurrence of SRIF SRIF synapses in this region; suggesting that SRIF exerts a negative feedback in the control of its own release through autoreceptors located on the perikarya or dendrites of SRIF-containing neurons. PMID- 2879255 TI - Buspirone decreases the activity of serotonin-containing neurons in the dorsal raphe in freely-moving cats. AB - Buspirone, a non-benzodiazepine anxiolytic agent, produced a dose-dependent decrease in the activity of serotonin-containing neurons in the dorsal raphe nucleus of freely-moving cats. The response ranged from no significant change at doses of 0.05 mg/kg to a nearly total suppression of activity at 1 mg/kg. These data suggest that the anxiolytic properties of buspirone may be mediated, at least part, by an action on neurons in the dorsal raphe. PMID- 2879254 TI - Antistereotype effects of ceruletide and some neuroleptics differentiated by interactions with clonazepam, muscimol, scopolamine and clonidine. AB - Compulsive gnawing was produced in mice by administration of either methylphenidate or (after sensitizing pretreatment with the neuroleptic, tetflutixol) apomorphine. Drugs which antagonise stereotypy, such as ceruletide (CER, a sulphated decapeptide related to cholecystokinin octapeptide), haloperidol, zuclopenthixol and fluphenazine were applied in equipotent doses (reducing stereotypy by 80%). Clonazepam, muscimol, clonidine and scopolamine (but not methylscopolamine) antagonized to a different extent the antistereotype effect of ceruletide and the neuroleptics. The ED50s for clonazepam and other drugs, were determined; clonazepam had the greatest potency. Regarding the antagonism of the antistereotype effect, ceruletide was similar to but by no means congruent with haloperidol. The antagonism of the antistereotype effect was specific because other effects of ceruletide and cholecystokinin octapeptide (inhibition of exploratory rearing activity, ptosis, antinociception, hypothermia) were not antagonized by clonazepam and only weakly modified by scopolamine. Methylscopolamine was ineffective throughout, indicating a central site for the mechanism of the actions studied of scopolamine. In conclusion, the antistereotype effect of ceruletide is different from that of conventional neuroleptic drugs and functionally independent of other behavioural effects of the cholecystokinin-like peptides. PMID- 2879256 TI - Reticular elicitation of hippocampal slow waves: common effects of some anxiolytic drugs. AB - Anxiolytic drugs share many of the common behavioural effects of septal and hippocampal lesions in animals. Gray attributes this to changes which the anxiolytics produce in septal generation of hippocampal rhythmical slow activity. However, lesions of the dorsal ascending noradrenergic bundle reproduce this electrophysiological effect of the anxiolytics while only reproducing part of the behavioural profile of the anxiolytics. The present paper reports what appears to be a second common effect of anxiolytic drugs on the generation of hippocampal slow waves which could underlie their behavioural effects. Freely moving rats, previously implanted with electrodes, received high frequency electrical stimulation of the midbrain reticular formation to elicit hippocampal rhythmic slow activity. The frequency of the slow waves produced increased linearly with increasing stimulation intensity as has been reported previously. A barbiturate (amylobarbitone, 15 mg/kg, i.p.) and three benzodiazepines (chlordiazepoxide, 5 mg/kg; diazepam, 5 mg/kg; alprazolam, 1 mg/kg) all decreased the slope of the voltage-frequency function and decreased overall frequency of slow waves produced. Two antipsychotic drugs (haloperidol, 0.2 mg/kg; chlorpromazine, 2 mg/kg) produced similar behavioural sedation to the anxiolytics but did not decrease either the slope of the voltage-frequency function nor the overall frequency of slow waves. The results show that these barbiturates and benzodiazepines produce a common reduction in the frequency of hippocampal rhythmical slow activity. Given the importance attached to slow waves in current theories of hippocampal function, it is possible that this electrophysiological effect could have some relation to the behavioural effects of these anxiolytic drugs. If the effect can be shown to generalize to other classes of anxiolytic drug it could reflect changes in the substrate for the common effects of anxiolytic drugs on behaviour. PMID- 2879257 TI - Multiple paragangliomas in neurofibromatosis: a new neuroendocrine neoplasia. AB - A pheochromocytoma, a glomus jugulare tumor, and multiple pulmonary paragangliomas were found in a patient with neurofibromatosis. We review the literature and add this case to the growing number of case reports of neurocutaneous disease in association with neuroendocrine tumors. PMID- 2879258 TI - Alzheimer's disease: low cerebral somatostatin levels correlate with impaired cognitive function and cortical metabolism. AB - Somatostatin-like immunoreactivity in Alzheimer CSF was significantly lower than in that from age-matched controls. The degree of reduction correlated with indices of intellectual impairment and decline in cortical glucose utilization as determined by PET. There was a close association between reduction in CSF somatostatin and glucose hypometabolism in the parietal lobe. In postmortem cortical tissue from Alzheimer patients, somatostatin levels were lower in posterior parietal but not in anterior frontal cortex. Loss of somatostatin containing neurons, especially in the parietal association cortex, may be a critical determinant for Alzheimer dementia. PMID- 2879259 TI - Use of serum creatine kinase, pyruvate kinase, and genetic linkage for carrier detection in Duchenne and Becker dystrophy. AB - Carrier detection in Duchenne dystrophy (DD) and Becker dystrophy (BD) can be achieved with DNA probes that recognize restriction fragment length polymorphisms (RFLPs). In 22 families, we found that 16 of 23 females at risk for being DD or BD carriers could be provided with more definitive indications of carrier status beyond the use of creatine kinase/pyruvate kinase and pedigree analysis. RFLP analysis was not possible for six individuals despite potentially informative probes, because family members critical to the analysis were unavailable. In only one instance were all eight probes uninformative. PMID- 2879260 TI - [Surgical radiology in stenosis of the epiaortic vessels: percutaneous transluminal angioplasty]. PMID- 2879261 TI - [Somatostatin in the treatment of upper digestive hemorrhage. Experience and controversy]. PMID- 2879263 TI - Neuropeptide Y-like immunoreactivity is absent from most perivascular noradrenergic axons in a marsupial, the brush-tailed possum. AB - Noradrenergic perivascular axons were demonstrated in all systemic arteries and veins of a marsupial, the brush-tailed possum (Trichosurus vulpecula), by a catecholamine fluorescence procedure and with antisera directed against the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and dopamine-beta hydroxylase (D beta H). Perivascular axons with neuropeptide Y-like immunoreactivity (NPY-LI) were not found in most systemic arteries and veins using antisera which recognize NPY and other members of the pancreatic polypeptide family in diverse vertebrate species. The exceptions were the renal, coeliac, main mesenteric and iliac arteries, where up to 50% of axons with TH-LI or D beta H-LI also showed NPY-LI with two of the 4 antisera used. No noradrenergic nerve cell bodies in thoracic sympathetic ganglia had NPY-LI, whilst 3% of noradrenergic nerve cell bodies in lumbar sympathetic chain ganglia had weak NPY-LI. This marsupial is the first vertebrate species found to date in which the majority of perivascular noradrenergic axons do not contain NPY-LI. If these axons contain an as yet unidentified neuropeptide, it is unlikely to be closely related to NPY. PMID- 2879262 TI - The ascending projections of the dopaminergic neurons of the substantia nigra, zona reticulata: a combined retrograde tracer-immunohistochemical study. AB - The efferent projections of the dopaminergic neurons in the zona reticulata of the substantia nigra were examined using a combined retrograde tracer immunohistochemical method. These dopamine (DA) neurons were found to project exclusively to striatal targets in a topographically defined fashion. The zona reticulata DA neurons do not innervate mesolimbic or mesocortical dopaminergic terminal fields, nor do they project to the superior colliculus or the ventromedial thalamic nucleus. These data suggest that the dopaminergic neurons of the zona reticulata represent a ventrally placed subset of the nigrostriatal DA cells of the pars compacta. PMID- 2879264 TI - Human fetal substantia nigra grafted to the dopamine-denervated striatum of immunosuppressed rats: evidence for functional reinnervation. AB - Human fetal substantia nigra tissue, obtained following therapeutic termination of first trimester pregnancies, was grafted to cavities overlying the striatum in ciclosporin-treated rats whose nigrostriatal dopamine system had been removed unilaterally by 6-hydroxydopamine. Tyrosine hydroxylase (TH) immunocytochemistry revealed large numbers of surviving human substantia nigra neurons that matured and formed TH-positive nerve fibers reinnervating the host rat striatum. Apomorphine-induced rotational behavior in grafted animals was reduced by 70-80% in optimal cases 3-5 months after grafting. Thus human fetal dopamine neurons can correct functional deficits in dopamine-denervated rat hosts. PMID- 2879265 TI - Evidence for a role of central type benzodiazepine receptors in the inhibition of the thyrotropin-releasing hormone-induced thyrotropin release from rat perifused pituitaries. AB - Several centrally active benzodiazepines (BZ) were tested for their ability to inhibit the TRH-induced secretion of TSH in vitro from perifused pituitaries. Diazepam, flurazepam, chlordiazepoxide (CDZ) and midazolam (10 nM) inhibited the TSH response to TRH (10 nM) by 33-50%, while medazepam, a prodrug having virtually no affinity for central BZ sites, did not. CDZ inhibition was reversed by Ro 15-1788, antagonist of the central type BZ binding sites, but not by PK 11195, antagonist of the peripheral type. The data are consistent with an involvement of central type BZ receptor sites in the TSH-lowering effects of BZ in rats. PMID- 2879267 TI - Acute psychosis: day patient treatment using rapid neuroleptisation. PMID- 2879266 TI - Inhibition of excitatory neurotransmission with kynurenate reduces brain edema in neonatal anoxia. AB - Excitatory amino acid neurotransmitters have been implicated in fostering brain edema and neuronal death in ischemia. As both of these processes are involved in nervous system damage during neonatal anoxia, the effect of blockade of cell excitation with kynurenate upon brain water was studied following anoxic-ischemic brain injury in neonatal rats. Such treatment attenuated brain edema immediately after, and 24 h following anoxia-ischemia. PMID- 2879268 TI - [Changes in bronchial blood flow and their role in fluid accumulation in experimental toxic pulmonary edema and ganglionic block]. PMID- 2879270 TI - Pvu II RFLP at the human chromosome 1 alpha-L-fucosidase gene locus (FUCA1). PMID- 2879269 TI - K+ -stimulated Na+ transport in frog-skin epithelia. AB - Increasing [K+] from 2.5 mmol/l to 115 mmol/l on the serosal side of the frog skin produces a rapid decrease of short-circuit current (Isc) that is followed, within a few minutes, by a recovery of Isc to near or above its control value. After isolation of the epithelium by a procedure involving collagenase treatment and physical removal of the corium, increasing serosal [K+] still produced a depression of Isc but no significant recovery phase. By itself, collagenase treatment reduced but did not eliminate the recovery phase. The recovery phase was also markedly depressed by the beta-adrenergic blocker oxprenolol, but not by propranolol, atropine or indomethacin. Amiloride, given during the recovery phase, caused Isc to reverse to a small outward value. These results suggest that the recovery phase of Isc seen in the response to increased serosal [K+] represents an increase in Na+ influx through amiloride-sensitive channels which is triggered by the release of an intermediary agent, possibly a beta-adrenergic agonist, from some structure in the corium. PMID- 2879271 TI - A PvuII RFLP for the human liver arginase (ARG1) gene. PMID- 2879272 TI - A polymorphic SstI site within the human ets-1 gene in the 11q23 region. PMID- 2879273 TI - Nebulized beta-adrenergic agents in the treatment of acute pediatric asthma. PMID- 2879274 TI - Interaction of somatostatin with isolated cytosol from rabbit renal papilla. AB - Specific binding sites for somatostatin have been characterized in cytosolic fraction of rabbit renal papilla. The interaction of 125I-Tyr11-somatostatin with cytosolic fraction was rapid, reversible, specific, saturable and dependent on temperature. At 25 degrees C the binding data were compatible with the existence of two classes of binding sites: a high-affinity class with a Kd = 57.7 nM and a low-affinity class with a Kd = 217.4 nM. Somatostatin binding sites exhibited a high degree of specificity since neuropeptides such as Leu-enkephalin, neurotensin, substance P, vasopressin and vasoactive intestinal peptide behaved as ligands with null or very low affinity. PMID- 2879275 TI - Neurotoxin effects on oxytocin, vasopressin and somatostatin in discrete rat brain areas. AB - Monosodium-L-Glutamate (MSG) produces lesions to monoaminergic and peptidergic neurons in several brain areas. The present study examined the effect of neonatal MSG treatment on oxytocin (OXY), arginine-vasopressin (AVP) and somatostatin (SRIF) concentrations in several discrete brain areas of adult rats. OXY increased in the suprachiasmatic and arcuate nuclei and median eminence (ME) and decreased in the paraventricular nucleus of MSG-treated rats. MSG treatment caused AVP to increase in the arcuate nucleus and ME and decrease in the supraoptic nucleus. SRIF decreased following neonatal MSG treatment in both the ME and neurointermediate pituitary lobe. The results demonstrate that the effects of neonatal MSG treatment on neuropeptide content are not just limited to the arcuate nucleus. Furthermore, taken together with previous results, the data suggest that these changes may be indicative of functional deficits in the neuronal activity of some of these peptidergic neurons which, in turn, may be responsible for the abnormal secretion of several pituitary hormones observed in MSG-treated animals. PMID- 2879276 TI - Opioid receptor binding profile of selected dermorphin-like peptides. AB - The receptor binding profile of a selected group of dermorphin-like peptides was determined and correlated with the results of the guinea pig ileum (GPI) and mouse vas deferens (MVD) bioassays and with the currently used antinociception tests in the rat. For the peptides with the characteristic dermorphin D-Ala2-Phe3 Gly4 sequence, a linear negative correlation was found between the reciprocal of sodium shift and relative affinity for the mu-type opioid receptor. For the same peptides, a positive correlation was evidenced between relative potency on GPI and MVD and relative affinity for mu- and delta-type receptors, respectively. PMID- 2879277 TI - Effect of CCK-8 on basal and meal-stimulated somatostatin in the baboon. AB - We measured the ability of CCK-8 alone, a test meal alone, or a combination of the two, to increase peripheral plasma somatostatin levels in the baboon. Baboons received a five-minute intravenous infusion of either CCK-8 (1, 2, or 4 micrograms/kg) or saline prior to a 30-minute meal. CCK-8 administration at all doses resulted in a significant rise of plasma somatostatin-like immunoreactivity (SLI). In addition, ingestion of a meal following a control saline infusion resulted in a significant rise of plasma SLI. However, the meal-related rise in SLI was blunted by prior administration of CCK-8 at all doses, including a dose which did not significantly decrease meal size. CCK-8 administration at all doses also blunted the meal-related rise of plasma insulin and glucose. We conclude that the known ability of CCK-8 to inhibit gastric emptying, as well as to decrease meal size, may account for its suppression of the meal-related SLI release. PMID- 2879278 TI - Differential sensitivity of hypothalamic and medullary opiocortin and tyrosine hydroxylase neurons to the neurotoxic effects of monosodium glutamate (MSG). AB - The distribution of opiocortin- (OP-ir) and tyrosine hydroxylase-immunoreactive (TH-ir) perikarya was examined immunocytochemically in rats treated neonatally with the neurotoxin monosodium glutamate (MSG). While OP-ir and TH-ir perikarya were eliminated in the arcuate nucleus in treated animals, the OP-ir and TH-ir cell groups of the nucleus tractus solitarius and contiguous medullary regions were unaffected. This selective elimination of arcuate neurons permitted us to examine specifically the fiber projections of the medullary OP-ir perikarya in treated animals. This revealed a preferential distribution of delicate fibers originating in NTS, to discrete medullary and pontine areas. In control animals, these same terminal fields appeared to be more densely populated with an additional population of thicker OP-ir fibers, suggesting the possibility of a shared innervation of these brainstem regions by both hypothalamic and medullary OP-ir neurons. PMID- 2879280 TI - Immunocytochemical localization of somatostatin in human brain. AB - The distribution of somatostatin (SRIF) was examined in normal human forebrain, using thick vibratome cut sections. The unlabeled antibody enzyme method of immunocytochemistry revealed a widespread distribution of SRIF immunoreactive neurons and fibers throughout the septum, diencephalon and corpus striatum. Within the septum SRIF neurons and fibers were observed in the medial and lateral septal nuclei, the nucleus of the diagonal band, the nucleus accumbens and the bed nucleus of the stria terminalis. SRIF neurons and fibers were found in several hypothalamic and anterior thalamic nuclei as well as all regions of the corpus striatum. An interesting collection of SRIF immunoreactive neurons and processes were observed forming a wide band extending anteriorly from the lateral preoptic area through the lateral hypothalamus and substantia innominata posteriorly. This report on the localization of immunoreactive SRIF in the human forebrain extends previous anatomical findings and lends morphological support to recent biochemical studies. PMID- 2879279 TI - Peptide transmitters of primary sensory neurons: similar actions of tachykinins and bombesin-like peptides. AB - Previous studies have demonstrated that two peptides, substance P (SP) and substance K (SK), are contained in a common prohormone--beta-preprotachykinin. Both peptides are cleaved from the prohormone and appear to coexist throughout the brain. This study evaluated the behavioral activity of SK and compared it to the activities of SP, bombesin (BN), and structurally related peptides. After intraspinal injection, all of the peptides induced "bite/scratch" behaviors, which differed in durations of action. The specific rank order of these durations of action were: BN greater than gastrin releasing peptide (GRP) = ranatensin (RT) greater than neuromedin B (NMB) greater than kassinin (KASS) = SK = SP and ranged from dose-dependent maxima of approximately 2 min (SP) to approximately 100 min (BN). To examine the possibility that differences in durations of action are due to differences in rates of proteolytic degradation, each peptide was incubated in spinal cord homogenates at 37 degrees C, and the degradation rates were monitored by radioimmunoassay (RIA) and by bioassay. The lengths of incubation time required to produce approximately 90% degradation of peptide immunoreactivity varied across peptides from less than 5 min (SP) to more than 60 min (BN and RT). Degradation of bioactivity generally paralleled degradation of immunoreactivity. The results of this study suggest that durations of nociceptive effects produced by the peptides tested are due, in part, to their resistance to proteolytic degradation. PMID- 2879281 TI - Polyarteritis nodosa and monocytic leukaemia. AB - A 67 year old man presented with a polyarteritis nodosa-like syndrome with renal, pulmonary joint and neurological involvement during the 'preleukaemic' stage of monocytic leukaemia. The association between these two conditions is discussed. PMID- 2879282 TI - The homeo domain of a murine protein binds 5' to its own homeo box. AB - Nuclear protein extracts from day 12.5 mouse embryos were used to study protein binding to DNA sequences 5' of the Hox 1.5 homeo box. Embryos of this developmental stage are known to express this gene. DNA binding protein blotting and retardation gel techniques show that murine embryonic nuclear proteins specifically bind a 753-base pair (bp) DNA fragment from the region upstream of the Hox 1.5 homeo box. A fusion protein containing the Hox 1.5 homeo domain constructed in lambda gt11 also binds the same 753-bp DNA fragment. Specific binding of the fusion protein to the upstream DNA fragment shows that the homeo box contains the sequences required for specific protein-DNA interactions, and the 753-bp fragment contains a homeo domain binding site. These results support the hypothesis that murine homeo boxes are DNA binding domains of proteins involved in the regulation of embryonic development. PMID- 2879283 TI - Genetic polymorphism and exon changes of the constant regions of the human T-cell rearranging gene gamma. AB - The genomic nucleotide sequences of the constant-region (C) genes of the human T cell rearranging gene gamma are given. These sequences show considerable allelic and nonallelic variation. Allelic variants exist at both C gamma 1 and C gamma 2 loci in coding regions (as well as in restriction enzyme sites). Both C gamma genes are in the same transcriptional orientation. Moreover, the organization of the nonallelic C gamma genes reveals some interesting features: the C gamma 1 gene, like the mouse C gamma gene, has three exons, whereas the C gamma 2 gene has four exons, including a duplicated second exon that would create a putative protein with an enlarged constant region. However, these two duplicated exons in C gamma 2 have lost the cysteine residue that is thought to be involved in the interchain disulfide bridge. PMID- 2879284 TI - Molecular studies of murine mutant BALB/c-H-2dm2 define a deletion of several class I genes including the entire H-2Ld gene. AB - Inbred mouse strains carrying spontaneous mutations in class I genes have been extremely informative in studies of the genetic mechanisms generating polymorphism in the major histocompatibility gene complex. In this report, we determine the molecular basis of the spontaneous loss mutation in BALB/c-H-2dm2 mice, which were previously shown not to express Ld antigens while maintaining normal expression of two other class I antigens, Kd and Dd. We show BALB/c-H-2dm2 mice do not transcribe detectable levels of Ld mRNA, indicating they do not produce a truncated Ld molecule as previously reported. Furthermore, in Southern blot comparisons using a series of low-copy genomic probes, the deletion was found to be approximately 140 kilobases and include the entire Ld gene along with three or more other class I genes mapping between Dd and Ld. These data represent direct genetic evidence for a spontaneous contraction in the genes encoding class I histocompatibility antigens, which in this case probably resulted from the misalignment of the 3' flanking regions of the Dd and Ld genes. PMID- 2879286 TI - Release of neuropeptides during intracellular stimulation of single identified Aplysia neurons in culture. AB - An important criterion for classifying a substance as a neurotransmitter is that it is released in an activity-dependent fashion. We have utilized cell culture of individual neurons of Aplysia to demonstrate the release of the neuropeptides SCPA and SCPB (small cardioactive peptides A and B). Neurons B1 and B2 were isolated from the buccal ganglion of Aplysia and maintained in cell culture. The cells grew new processes, which were immunoreactive to antibodies for the neuropeptide SCPB. These processes contained SCPA and SCPB that were detectable by bioassay on snail heart. The cells synthesized the SCPs from radiolabeled precursors and transported the peptides to their neurites. Single cells released SCPs in a calcium-dependent fashion upon intracellular electrical stimulation. Taken together, these results provide critical evidence that SCPs are neurotransmitters. The results also indicate that the cell culture of individual identified neurons can be used to investigate the release of peptides. PMID- 2879285 TI - Glucocorticoid receptor immunoreactivity in monoaminergic neurons of rat brain. AB - A monoclonal antibody against the rat liver glucocorticoid receptor was used in combination with rabbit antibodies against tyrosine hydroxylase, phenylethanolamine N-methyltransferase, and 5-hydroxytryptamine to demonstrate strong glucocorticoid receptor immunoreactivity in large numbers of central monoaminergic nerve cell bodies of the male rat. The receptor immunoreactivity was predominantly located in the nucleus, whereas the tyrosine hydroxylase, phenylethanolamine N-methyltransferase, and 5-hydroxytryptamine were detected mainly in the cytoplasm. The vast majority of the noradrenergic nerve cell bodies of groups A1-A7 and of the 5-hydroxytryptaminergic cell bodies of groups B1-B9 were found to contain strong glucocorticoid receptor immunoreactivity. The majority of the phenylethanolamine N-methyltransferase-immunoreactive nerve cells of the adrenergic cell groups C1-C3 and of the dorsal subnuclei of the nucleus tractus solitarius in the medulla oblongata were also strongly immunoreactive for glucocorticoid receptor. In the midbrain dopaminergic groups A8-A10, moderately (A8, A9) to strongly (A10) glucocorticoid receptor-immunoreactive cells were found, ranging from 40 to 75% of the total population. In the hypothalamic dopaminergic cell groups, all the cells of groups A12 and A14, as well as the majority of the dopaminergic cells of the zona incerta (A13), were found to contain moderate to strong glucocorticoid receptor immunoreactivity, but none of the large dopaminergic cells of the posterior hypothalamus (A11) showed such immunoreactivity. PMID- 2879288 TI - Isolation of pyroGlu-Gly-Arg-Phe-NH2 (Antho-RFamide), a neuropeptide from sea anemones. AB - A radioimmunoassay has been developed for peptides containing the carboxyl terminal sequence Arg-Phe-NH2 (RFamide). Using this radioimmunoassay and applying cation-exchange chromatography and HPLC, we have isolated an RFamide peptide from acetic acid extracts of the sea anemone Anthopleura elegantissima. Three different methods established that the structure of the Anthopleura RFamide peptide (Antho-RFamide) is pyroGlu-Gly-Arg-Phe-NH2. Comparison of synthetic and natural Antho-RFamide and their enzymatic breakdown products on six different HPLC columns confirmed the structure of the sea anemone peptide. Using synthetic Antho-RFamide as a standard in our radioimmunoassay, we measured high concentrations (3.2 nmol/g wet weight) of this peptide in extracts of Anthopleura. It is proposed that Antho-RFamide is a transmitter at neuromuscular synapses in sea anemones. PMID- 2879287 TI - Hormonal modulation of the quantity and in situ activity of tyrosine hydroxylase in neurites of the median eminence. AB - The role of ovarian hormones in the control of the quantity and activity of tyrosine hydroxylase (TyrOHase) in neurites of the median eminence of the rat was investigated. TyrOHase was quantified by an immunoblot assay using purified rat TyrOHase as the standard. Treatment of ovariectomized animals with progesterone, but not estradiol, resulted in a significant reduction in the amount of TyrOHase in the median eminence. The in situ activity of the enzyme was assayed by measuring the rate of synthesis of L-3,4-dihydroxyphenylalanine (dopa), and the results were expressed as mol of dopa per hr per mol of TyrOHase. In animals treated with both estradiol and progesterone for 3 days, the in situ activity of TyrOHase in the median eminence was 114 +/- 13.5 (mean +/- SEM) compared to 26 +/ 4.7 for the controls. Estradiol or progesterone alone was much less effective than was the combination of estradiol and progesterone. To ascertain whether the effect of estradiol and progesterone on TyrOHase activity was reflected in the secretion of dopamine into hypophyseal portal blood, ovariectomized rats were treated for 3 days with both estradiol and progesterone or with the solvent vehicle. The concentration of dopamine in portal plasma of the hormone-treated animals was 1.93 +/- 0.533 ng/ml compared to 0.34 +/- 0.094 ng/ml in vehicle treated animals. We conclude that the quantity and in situ molar activity of TyrOHase in neurites of the median eminence as well as the secretion of dopamine from these neurites are modulated by the combined action of estradiol and progesterone. PMID- 2879290 TI - Interaction of human pancreatic growth hormone-releasing factor, thyrotropin releasing hormone, and somatostatin on growth hormone release in chickens. AB - The effects of synthetic somatostatin (SRIF) on serum growth hormone (GH) concentrations stimulated by exogenous administration of synthetic thyrotropin releasing hormone (TRH) and/or human pancreatic GH-releasing factor (hpGRF) were investigated in 4-week-old cockerels. In addition, the additive effects of TRH and hpGRF on serum GH were examined. TRH and hpGRF, when given in combination intravenously, produced an additive effect on serum GH concentration that peaked 10 min after the injection. The somatostatin did not significantly affect basal GH concentrations when given alone, but did significantly decrease the magnitude of the GH response to hpGRF. In contrast, SRIF did not significantly decrease the stimulatory effects of TRH on GH release. These results suggest that TRH and hpGRF are potent GH releasers in vivo and that their stimulating effects on GH release are additive, suggesting different mechanisms for their stimulation. The results obtained from the combination studies suggest that the main site of the stimulatory action of hpGRF is at the pituitary, and that SRIF significantly inhibited the rise in serum GH induced by a synthetic hpGRF, but not that induced by TRH. PMID- 2879289 TI - Differences in tyrosine hydroxylase-like immunoreactivity characterize the mesostriatal innervation of striosomes and extrastriosomal matrix at maturity. AB - Tyrosine hydroxylase [TyrOHase, tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (2-hydroxylating), EC 1.14.16.2] is the rate-limiting enzyme in the synthetic pathway of catecholamines and is expressed by neurons containing dopamine, norepinephrine, and epinephrine. TyrOHase is present in high concentrations in the caudate nucleus and putamen, where nearly all of it is contained in axons of the dopaminergic mesostriatal pathways. We have employed three different polyclonal antibodies directed against TyrOHase, one tested here for specificity by two-dimensional gel electrophoresis, to reexamine the anatomic distribution of fibers expressing TyrOHase-like immunoreactivity in the striatum of mature human, monkey, and cat brains. The findings suggest that this distribution is distinctly inhomogeneous. The macroscopic compartments known as striosomes have low TyrOHase-like immunoreactivity relative to the surrounding extrastriosomal matrix. These observations add to evidence that dopaminergic modulation of neural processing in the mature striatum is organized in accordance with striosomal architecture and suggest that part of the mechanism for such differentiation may involve presynaptic differences in enzymatic regulation of dopamine content in and out of striosomes. PMID- 2879291 TI - Different changes of n-6 and n-3 fatty acids in adipose tissue from spontaneously hypertensive (SHR) and normotensive rats after diets supplemented with linolenic or eicosapentaenoic acids. AB - In spontaneously hypertensive (SHR) and normotensive rats of the Wistar-Kyoto (WKY) and Wistar-Schonwalde (WSCHOE) strain, diets supplemented with n-3 fatty acids of different chain length (alpha-linolenic acid, LNA--C 18:3, n-3 with linseed oil and eicosapentaenoic acid, EPA--C 20:5, n-3 with cod liver oil) were fed over a period of 22 weeks. After the LNA-rich diet, among the long-chain n-3 fatty acids EPA in epididymal adipose tissue remained unchanged, whereas docosapentaenoic (DPA) and docosahexaenoic acids (DHA) fell. The n-6 fatty acids linoleic (LA) and arachidonic acid (AA) both appeared decreased. After the EPA rich diet, all n-3 fatty acids, i.e. not only EPA, DPA and DHA, but also LNA were augmented when compared with controls fed commercially available pellets. Among the n-6 fatty acids LA was extremely depressed, whereas AA appeared increased. The p/s-ratio was elevated after the LNA-rich diet, but decreased after the EPA rich diet. The data indicate a differential effect of dietary n-3 fatty acids of different chain length on the supply of other n-3 fatty acids, of LA and AA as well as on the p/s-ratio in adipose tissue of rats. Blood pressure was not influenced by either diet in either SHR or in both normotensive strains of rats. PMID- 2879292 TI - Slow desaturation and elongation of linoleic and alpha-linolenic acids as a rationale of eicosapentaenoic acid-rich diet to lower blood pressure and serum lipids in normal, hypertensive and hyperlipemic subjects. AB - In normal, hypertensive and hyperlipemic subjects, diets supplemented with linoleic acid (LA) or alpha-linolenic acid (LNA) resulted in an increase of the corresponding fatty acids in serum lipids. However, their C20-derivatives, the prostaglandin precursors arachidonic acid (AA) and eicosapentaenoic acid (EPA), respectively, were not or only slightly augmented. On the other hand, an EPA-rich diet produced a marked increase of this fatty acid, especially in cholesterol esters. After this diet the decreases of blood pressure and serum lipids were more pronounced when compared with LA- and LNA-rich diets containing a 20-fold higher dose of the polyunsaturated fatty acids. The slow formation of AA and EPA from LA and LNA seems to be a characteristic finding in humans, being different from preferred laboratory animals, for instance, rats. This observation was independent of the presence of risk factors, like arterial hypertension or hyperlipoproteinemia (HLP). PMID- 2879293 TI - Hypotensive effect in dogs and rats of intravenous injections of the alpha 1 adrenoreceptor antagonist benoxathian. AB - The hypotensive effect of the alpha 1-adrenoreceptor antagonist benoxathian has been evaluated in rats and dogs, in comparison to that evoked by WB 4101 and prazosin. In anaesthetized dogs, i.v. injection of benoxathian (25-100 micrograms/kg), WB 4101 (5-25 micrograms/kg) and prazosin (50 micrograms/kg) produced an immediate fall in diastolic blood pressure, which reached a maximum at about 30 sec after drug administration. Whereas the hypotensive effect of prazosin persisted up to 3 hr following injection, the effect of both benoxathian and WB 4101 completely disappeared after 30-60 min. The hypotensive effect of benoxathian was dose-dependent. Pressor responses to i.v. noradrenaline (5 micrograms/kg), adrenaline (5 micrograms/kg) and phenylephrine (20 micrograms/kg) were markedly inhibited (60-75%) by benoxathian (100 micrograms/kg) whilst the pressor response to angiotensin II (0.05 micrograms/kg) was not reduced, but indeed slightly increased. The hypotensive effect of benoxathian (100 micrograms/kg) was abolished following pre-treatment with prazosin (50 micrograms/kg) or hexamethonium (1000 micrograms/kg). In anaesthetized rats similar results were obtained although recovery in blood pressure from the initial drop after i.v. injection of the drugs was slower than in dogs. Benoxathian was slightly more toxic than WB 4101 in rats. In conclusion, present findings show that benoxathian causes a profound hypotensive effect in dogs and in rats through postsynaptic alpha-adrenoreceptor blockade; however its effect, as well as that of WB 4101, is shorter lasting than that of prazosin. PMID- 2879294 TI - Spectrophotometric determination of some 1,4-benzodiazepines by use of orthogonal polynomials. AB - A direct spectrophotometric method for the determination of some 1,4 benzodiazepines, namely, nitrazepam, prazepam and dipotassium chlorazepate, in the presence of their degradation products, is presented. The method depends upon the use of orthogonal polynomials, to eliminate interferences by degradation products to the absorption spectra of the intact drugs. The method was proved using synthetic mixtures of the intact drugs with their respective degradation products and its suitability to monitor for the stability of the drugs was demonstrated. The method has been applied to the determination of these drugs in dosage forms, with a coefficient of variation less than 2%. PMID- 2879295 TI - The structural characterization of beta-endorphin and related peptide hormones and neurotransmitters. PMID- 2879296 TI - Can changes in eye-contacts predict therapeutic outcome in schizophrenic patients undergoing neuroleptic treatment? Results of a preliminary study. AB - The proportion of interview time spent in eye-contacts was studied before the onset of and during neuroleptic treatment in a group of 24 male schizophrenic patients. A significant increase in eye-contacts after 14 days distinguished responders to neuroleptic treatment, while a tendency towards the same effect distinguished patients treated with haloperidol from those treated with perazine. Only in the subgroup of responders was there a significant relationship between increase in eye-contacts and reduction of psychopathologic symptoms, regardless of whether these values were compared for the same treatment days or whether early changes in eye-contacts were compared with final outcome of treatment after 28 days. Since the patient subgroups were rather small, the results should still be considered preliminary. A prospective study including more parameters of visual interaction, a larger patient sample, and a longer observation period is required. PMID- 2879297 TI - Quantitative EEG, SPEM, and psychometric studies in schizophrenics before and during differential neuroleptic therapy. PMID- 2879299 TI - Phytochrome and the regulation of the expression of its genes. AB - In attempting to understand the mechanism of phytochrome action we are studying structural properties of the photoreceptor molecule and the autoregulation of expression of phytochrome genes. Run-off transcription assays in isolated nuclei from Avena indicate that phytochrome decreases the transcription of its own genes threefold in less than 15 min form Pfr formation. The extent of this decrease is insufficient to account for the observed 10- to 50-fold decrease in mature phytochrome mRNA levels, suggesting that enhanced degradation may also play a significant role in determining the level of this mRNA. Structural analysis of native phytochrome from Avena indicates that the molecule is an elongated dimer of 124 kDa monomers, each consisting of a globular, 74 kDa, NH2-terminal domain bearing the single chromophore at Cys-321, and a more open COOH-terminal domain that bears the dimerization site. Controlled proteolysis and binding of monoclonal antibodies to mapped epitopes has identified two regions, one in the 6 10 kDa NH2-terminal segment and the other ca. 70 kDa from the NH2-terminus, that undergo photoconversion-induced conformational changes and are therefore candidates for involvement in the molecule's regulatory function. Comparison of the full-length amino acid sequences of Avena and Cucurbita phytochromes, derived from nucleotide sequence analysis, indicates overall homology of 65%. The most highly conserved regions are those immediately surrounding the chromophore attachment site, where 29 residues are invariant, and a hydrophobic region between residues 150 and 300, postulated to form a cavity containing the chromophore. In contrast, a strikingly lower level of homology exists at the COOH terminus of the polypeptide between residues 800 and 1128, indicating a possible lack of involvement of this region in phytochrome function. PMID- 2879298 TI - Auxin-regulated gene expression. AB - During the 1960s a wide range of studies provided an information base that led to the suggestion that auxin-regulated cell processes--especially cell elongation- may be mediated by auxin-regulated gene expression. Indirect evidence from our work, based on the influence of inhibitors of RNA synthesis (e.g. actinomycin D) and of protein synthesis (e.g. cycloheximide) on auxin-induced cell elongation, coupled with correlations of the influence of auxin on RNA synthesis and cell elongation, provided the basis for this suggestion. With the availability of techniques for DNA-DNA and DNA-RNA hybridization, mRNA isolation-translation, in vitro 2D gel analysis of the translation products, and ultimately the cloning by recombinant DNA technologies of genomic DNA and copy DNAs (cDNAs) made to poly(A)+ mRNAs, we and others have provided direct evidence for the influence of auxin on the expression of a few genes (i.e. poly(A)+ RNA levels). Our laboratory has provided evidence for auxin's both down-regulating and up-regulating the level of a few poly(A)+ mRNAs out of a population of about 4 X 10(4) sequences that are not significantly affected by auxin. In our studies on auxin-regulated cell elongation, two cDNA clones (pJCW1 and pJCW2) were isolated which corresponded to poly(A)+ mRNAs that responded during growth transitions in a way consistent with a potential role of their protein products in cell elongation. These mRNAs are most abundant in the elongating zone of the soybean hypocotyl. Upon excision and incubation in the absence of auxin, these mRNAs deplete in concert with a decreasing rate of cell elongation. Addition of auxin to the medium results in both increased levels of these mRNAs and enhanced rates of cell elongation. These mRNAs do not deplete if auxin is added to the medium at the onset of excised incubation, and cell elongation rates remain high. We have isolated and sequenced genomic clones that are homologous to these cDNAs. Of the two genes sequenced, both genes are members of small multigene families. There are regions of high amino acid homology even though the nucleotide sequences are sufficiently different in these regions for cross-hybridization of the clones not to be observed. More recently others, especially Guilfoyle's laboratory, have shown that auxin selectively and rapidly influences the level of certain mRNAs and proteins. We have worked on other gene systems such as ribosomal proteins and possible cell wall proteins that are responsive to auxin; again the nature of regulation of expression of these genes is not known.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2879300 TI - Effects of soyasaponins on liver tyrosine aminotransferase activity induced by cortisone in adrenalectomized rats. PMID- 2879301 TI - Do neuroleptics prevent relapse? Clinical observations in a psychosocial rehabilitation program. PMID- 2879302 TI - Multiple forms of the D1 dopamine receptor: its linkage to adenylate cyclase and psychopharmacological effects. PMID- 2879303 TI - Structural analogs of SCH 23390 as discriminators of dopamine receptor subtypes: behavioral interactions between D-1 and D-2 agonists and antagonists. PMID- 2879304 TI - Biochemical and behavioral studies of D1 dopamine receptors utilizing SCH 23390. PMID- 2879305 TI - Molecular aspects of benzodiazepine receptor function. PMID- 2879306 TI - Suicidal potential in depression: focus on CSF monoamine and purine metabolites. PMID- 2879308 TI - Interpersonal and pharmacologic treatment in schizophrenia: a comparative study of new approaches. PMID- 2879307 TI - Nonbenzodiazepine anxiolytics: insights into possible mechanisms of action. PMID- 2879309 TI - Medication, family psychoeducation, and social skills training: first year relapse results of a controlled study. PMID- 2879310 TI - Supersensitivity psychosis and tardive dyskinesia: a survey in schizophrenic outpatients. PMID- 2879311 TI - Associations among plasma prolactin levels, tardive dyskinesia, and paranoia in treated schizophrenics: relevance to supersensitivity psychosis. PMID- 2879312 TI - Basic and clinical studies of neuroleptic-induced supersensitivity psychosis and dyskinesia. PMID- 2879313 TI - Effects of drug washout on CSF monoamine and psychoendocrine variables. PMID- 2879314 TI - Anticholinergic prophylaxis in young adults treated with neuroleptic drugs. PMID- 2879316 TI - Percutaneous transluminal angioplasty for renovascular hypertension in arteritis: experience in China. AB - Forty-two patients with renovascular hypertension were treated with percutaneous transluminal angioplasty. In 32, arteritis was the cause of the renovascular disease. Thirty of the 42 patients were followed for more than 6 months after angioplasty. Twenty-two of these 30 patients had arteritis; 19 of the 22 (86.4%) benefited from the angioplasty, compared with six of eight patients (75%) with atherosclerosis or fibromuscular dysplasia. PMID- 2879315 TI - Benzodiazepines in schizophrenia. PMID- 2879317 TI - CSF neurotransmitter markers in Alzheimer's disease. AB - CSF neurotransmitter markers may reflect neurochemical alterations in Alzheimer's disease (AD). The best studied neurochemical deficit in AD is that of acetylcholine. Both acetylcholinesterase and butyrylcholinesterase activity have been reported to be reduced in some but not all studies of AD CSF. Studies of monoamine metabolites have also been controversial but most authors have found reduced concentrations of CSF HVA, lesser reductions in HIAA and no change in MHPG. CSF GABA concentrations have been found to be reduced in AD. Studies of CSF neuropeptides in AD have shown reduced concentrations of somatostatin and vasopressin, normal concentrations of vasoactive intestinal polypeptide and either normal or decreased concentrations of beta-endorphin and corticotropin releasing factor. Although no individual CSF neurochemical markers are specific for AD it may be possible to develop a profile of several neurochemical markers which will have enhanced specificity. PMID- 2879318 TI - On the pathogenesis and therapy of dementia of the Alzheimer type: some neuropathological, biochemical, genetic and pharmacotherapeutic considerations. AB - The extensive literature on dementia of Alzheimer type (DAT) testifies to the enormous progress achieved in the clinical and biochemical delineation of this disease. Newly developed laboratory and imaging techniques are also being applied to the diagnosis of DAT. Nevertheless, unequivoval diagnosis still relies primarily on morphological data from biopsy or autopsy. An overview is presented of major morphological changes occurring at different levels of organization in the central nervous system (CNS) in DAT. Currently formulated etiopathogenic hypotheses of DAT are reviewed and discussed in the context of morphological alterations. Some of the recombinant DNA methods, that are currently available for gene analysis, are described. Some approaches for studying Alzheimer specific genes using the above methods have been suggested. Finally, a critical overview of the current pharmacotherapeutic armamentarium used in DAT and senile dementia is presented. The efficacy, side effects, and the main mechanisms of action of the two categories of drug therapy -supposed etiopathogenic and symptomatic- are presented. PMID- 2879319 TI - Are the neurochemical and behavioral changes induced by lesions of the nucleus basalis in the rat a model of Alzheimer's disease? AB - A review of the work on the neurochemical, electroencephalographic and behavioral changes induced in the rat by lesions of the nucleus basalis is presented. The similarities and differences between the effects of the lesions and the neurochemical and clinical alterations characterizing senile dementia of Alzheimer type are pointed out. The decrease in choline acetyltransferase (ChAT) activity in the cortex following unilateral or bilateral electrolytic or neurotoxic lesions of the nucleus basalis are described and compared with the decrease in ChAT activity found in the cortex and hippocampus of patients affected by senile dementia. At variance with the latter condition, in rats with lesions of the nucleus basalis a spontaneous recovery in cortical ChAT activity has been observed 3-6 months after the lesion. The lesions of the nucleus basalis decrease high affinity choline uptake activity which, however, undergoes a rapid recovery. Lesions also decrease spontaneous and drug-stimulated ACh release from the cerebral cortex. Transitory changes in the number of muscarinic binding sites have been reported in the cerebral cortex of the lesioned rats while a decrease in the number of muscarinic binding sites has generally been found in the cerebral cortex of patients with senile dementia. [3H] glutamate uptake in the striatum of the lesioned rats was not affected. In both lesioned rats and patients affected by senile dementia, a decrease of low voltage high frequency electrocortical activity has been reported. Unilateral and bilateral lesions of the nucleus basalis bring about an impairment of the acquisition of active and passive avoidance responses and of the rewarded alternation discriminatory tasks involving working memory and spatial memory. On the other hand, memory impairment is a typical symptom of senile dementia. In conclusion, the lesions of the nucleus basalis only partly mimic the complex clinical picture of senile dementia of Alzheimer type. They offer, nevertheless, a useful tool for understanding the critical role of the central cholinergic pathways in some of the cognitive processes and identifying potentially useful pharmacological treatments. PMID- 2879321 TI - [Association of a thoracic carcinoid tumor and hyperparathyroidism]. PMID- 2879320 TI - [Analysis of developmental pattern of neurotransmitters and receptors using primary cultured neurons: with special reference to GABAergic neurons]. PMID- 2879322 TI - [Study of the relative stability of urban mosquito breeding grounds on the basis of indices of diversity, equitableness and richness of species]. PMID- 2879324 TI - [Therapy of epileptic psychoses]. PMID- 2879323 TI - [Somatostatin. Massive upper digestive hemorrhage in portal hypertension. Results of a controlled study]. PMID- 2879325 TI - Flumezapine, an antagonist of central dopamine and serotonin receptors. AB - Flumezapine, 7-fluoro-2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3- b] [1,5]benzodiazepine, antagonized the increases in serum corticosterone concentration caused by a serotonin agonist, quipazine, and by a dopamine agonist, pergolide, in rats. Flumezapine did not alter the elevation of serum corticosterone by a kappa opioid agonist, bremazocine. Flumezapine resembled but was more potent than clozapine and zotepine in blocking these effects of quipazine and pergolide, differing from spiperone and fluphenazine which were selective antagonists of pergolide and from metergoline and mianserin which were selective antagonists of quipazine. All of the antagonists had high affinity for 5HT2 receptors as measured by radioligand-binding in vitro. Spiperone, fluphenazine, zotepine and flumezapine had high affinity for dopamine D2 receptors as measured by radioligand-binding in vitro. The potency of the compounds in antagonizing the pergolide-induced elevation of serum corticosterone concentration matched their affinity for D2 receptors in vitro. There was poor correlation between the potency of the compounds in antagonizing the quipazine induced elevation of serum corticosterone concentration and their affinity for 5HT2 receptors in vitro, possibly indicating that the receptor mediating the effect of quipazine is not identical to or exclusively the 5HT2 receptor. The results suggest that flumezapine is a potent blocker of dopamine D2 and of some serotonin receptors. PMID- 2879326 TI - Effects of corticosterone and metyrapone on gastrointestinal neurotransmitter enzyme activities. AB - Adrenal glucocorticoids have been shown to produce alterations in the enzymes which synthesize and degrade cholinergic and catecholaminergic neurotransmitters in the central and peripheral nervous system. The present study examined the impact of altering plasma corticosterone levels via corticosterone or metyrapone ingestion, via the drinking water, on the developmental profile of choline acetyltransferase (ChAT), acetylcholine esterase (AChE), tyrosine hydroxylase (TH) and monoamine oxidase (MAO) in various gastrointestinal (GI) segments of rats. Three groups were studied: non-treated, corticosterone treated and metyrapone treated. Drug intake of pregnant (i.e., beginning on the 15th day of gestation), lactating and weaned rats was monitored until the male pups were sacrificed at 1, 3, 7, 14, 21, 35 and 50 days of age. Results showed that ChAT and TH activities peaked earlier in development in corticosterone treated rats as compared to non-treated and metyrapone treated rats. During the early postnatal period plasma corticosterone levels were inversely related to AChE and MAO activities in most GI segments. These results indicate that neurotransmitter enzyme activities in various GI segments are influenced by corticosterone during a critical period of development. PMID- 2879327 TI - Evaluation of alpha-adrenergic cardiac stimulation in anesthetized dogs: can this play a role in propranolol insensitive cardiostimulatory effects of celiprolol. AB - The role of alpha-adrenergic systems in modulating contractility and rate in the canine heart is not completely understood. This was evaluated by examining alpha agonists and antagonists in ganglionic- and beta-blocked, anesthetized dogs. Also, partial agonist effects of the beta-blocker celiprolol in the ganglionic blocked dog are insensitive to propranolol and may be mediated via alpha-2 antagonism. Prazosin (0.3 mg/kg), yohimbine (0.3 mg/kg), celiprolol (3 mg/kg) and vehicle were administered to ganglionic-(mecamylamine 2 mg/kg) and beta adrenergic-(propranolol 1 mg/kg + 0.3 mg/kg/hr) blocked dogs. Clonidine (0.3 and 3.0 micrograms/kg), phenylephrine (3 micrograms/kg) and norepinephrine (0.3 microgram/kg) produced significant increases in arterial pressure with minimal chronotropic or inotropic effects. Celiprolol produced sustained increases in heart rate and contractile force of 15 +/- 3 beats/min and 33 +/- 7 percent (X +/ SEM) without significant vascular alpha antagonism. Yohimbine, prazosin and vehicle were without significant chronotropic or inotropic effects. However, yohimbine and prazosin selectively reduced pressor responses to clonidine and phenylephrine, respectively. In further studies adding prazosin or phentolamine before treatment with celiprolol did not attenuate its effects on heart rate and contractility. These results do not support significant inotropic or chronotropic effects of alpha-adrenergic receptor modulation in anesthetized dogs. The cardiac stimulatory effects of celiprolol do not appear to be mediated via cardiac alpha receptors. PMID- 2879328 TI - Hexamethonium aerosol prevents pulmonary reflexes induced by cigarette smoke in dogs. AB - The reflexogenic respiratory responses to spontaneous inhalation of cigarette smoke (500-750 ml, 12-20% concentration) were studied in chloralose anesthetized dogs before and after hexamethonium aerosol, a nicotinic receptor antagonist, was administered into the lungs. In 11 of 13 dogs studied, reproducible responses of either apnea (n = 9) or rapid shallow breathing (n = 2) were elicited immediately after the first or second breath of smoke inhalation: apneic duration reached 398 +/- 47% (mean +/- SEM) of the mean baseline expiratory duration. Pretreatment with hexamethonium aerosol (3-5 breaths, 10% concentration) completely abolished these immediate changes in breathing patterns, but did not significantly reduce the delayed hyperpnea induced by smoke inhalation. Hexamethonium aerosol alone did not cause any detectable systemic effects. To examine if a bronchoconstrictive effect of nicotine was involved, the response to cigarette smoke was also studied after bronchodilation was induced by isoproterenol aerosol (15 breaths, 0.5% concentration) in 6 of these dogs. However, neither immediate nor delayed responses to smoke inhalation was significantly affected. These results suggest that: (1) these immediate respiratory responses to smoke inhalation are elicited by a nicotine-induced stimulation of vagal sensory receptors in the lungs, and (2) bronchoconstriction is not responsible for causing these reflex effects. PMID- 2879329 TI - European general practice research workshop (EGPRW). Is international cooperation worth while? AB - General practice is a novice in the academic world. We need to stand together both nationally and internationally to establish general practice as a true academical discipline. To strengthen our credibility we have to do research of high quality. European General Practice Research Workshop (EGPRW) is a partly unformal international body with the aim "to encourage research, to foster and coordinate multinational studies, to exchange experiences and with it develop a validated international scientific base for general practice". The group was established November 1974 and the activities during its short existence are summarised and commented. PMID- 2879330 TI - In vivo and in vitro studies on the physiology of penile erection. PMID- 2879331 TI - [Electrocardiographic diagnosis of myocardial infarction of the right ventricle. Clinico-electrocardiographic correlations]. PMID- 2879332 TI - [Repeat myocardial infarction and reinfarction. Clinical, developmental and peculiar anatomopathologic aspects]. PMID- 2879333 TI - [Unusual forms of clinico-biological manifestations in the post-infarction syndrome (Dressler)]. PMID- 2879334 TI - [Changes in plasma AGL during physical effort: effects of nifedipine, propranolol and a combination of propranolol and nifedipine on these changes]. PMID- 2879335 TI - [Thoracic pain syndrome appearing after acute myocardial infarction]. PMID- 2879337 TI - [Organization and efficiency of a unit for the management of arterial hypertension]. PMID- 2879336 TI - [Electrocardiographic characteristics in alcoholic cardiomyopathies]. PMID- 2879338 TI - [Vasodilators in decompensated chronic cor pulmonale]. PMID- 2879339 TI - [Difficulties in the electrocardiographic and vectorcardiographic diagnosis of a case of Wolff-Parkinson-White syndrome associated with recurrent myocardial infarction and bifascicular block]. PMID- 2879341 TI - [Forced microbial stimulation in respiratory infections]. PMID- 2879340 TI - [Changes in platelet functions and blood coagulation in patients with bronchopulmonary cancer]. PMID- 2879342 TI - [Pathology of cellular receptors]. PMID- 2879343 TI - [Intentional drug poisoning from the epidemiological, emergency medical and therapeutic viewpoints]. PMID- 2879344 TI - [Double-blind treatment of 49 cases of chronic multiple sclerosis using hyperbaric oxygen]. AB - Forty nine patients with a chronic form of multiple sclerosis (MS) [progressive or stable] were treated with hyperbaric oxygen (HO) in a double blind trial. Patients were divided in three groups: the first group (group I) received a course of 2.3 ATA HO with diazepam (5 mg); the second group (group II) received a course of 2 ATA HO; the third group (group III) was the control group. Each patient breathed an adapted gaseous mixture in high pressure. Each patient received 20 sessions of this procedure during 4 weeks. Patients were evaluated with clinical, neurophysiological and immunological parameters. Clinical examination consisted in the evaluation of the Kurtzke's Disability Status Scale (DSS) and Functional Status Scale (FSS). This evaluation was done in the week before the procedure, the week following the treatment, then in the third and sixth month. The neurophysiological study was a comparative analysis from the variations of visual, somesthesic and brain stem auditory potentials. The immunological study was the analysis of the lymphocyte populations (OKT4/OKT8 ratio). Each examination was carried out the week before, then the week following the procedure. We found no amelioration into three groups. Subjectively, some patients thought to be better, but this was true in the two treated groups (I, II) and in the control group (III). There was not an FSS significant variation. We also found no significant variation of evoked potentials and OKT4/OKT8 ratio. We observed some incidental effects of the treatment, particularly in group I, in which patients were treated with a higher pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879345 TI - A randomized controlled trial of ampicillin plus sulbactam vs. gentamicin plus clindamycin in the treatment of intraabdominal infections: a preliminary report. Study Group of Intraabdominal Infections. AB - This is a preliminary report of a comparative study of sulbactam plus ampicillin (sulbactam/ampicillin) vs. gentamicin plus clindamycin (gentamicin/clindamycin) in surgically treated patients with intraabdominal infections. Among 46 assessable patients in the sulbactam/ampicillin group, 40 were clinically cured or improved as compared with 36 of 37 patients in the gentamicin/clindamycin group. Among 40 microbiologically assessable patients in the sulbactam/ampicillin group, the pathogen was eradicated in 33 patients and partially eradicated in two, whereas eradication was recorded in 21 and partial eradication in 10 of the 32 patients in the gentamicin/clindamycin group. Among 150 aerobic isolates, 14 were resistant to sulbactam/ampicillin, 27 were resistant to gentamicin/clindamycin, and 85 were beta-lactamase producers. No resistance to sulbactam/ampicillin was found in 75 anaerobic isolates, whereas one anaerobic isolate was resistant to clindamycin. This preliminary report suggests that ampicillin/sulbactam is a useful nontoxic alterative to gentamicin/clindamycin in the treatment of intraabdominal infections. PMID- 2879346 TI - [Multiple endocrine adenomatosis types I and II]. PMID- 2879347 TI - [Diagnosis and clinical course of periarteritis nodosa]. AB - The clinical symptoms, diagnostic procedure and course under treatment in 10 patients with polyarteritis nodosa are studied retrospectively. Clinically, 3 patients showed peripheral arterial occlusive disease in the lower extremities. 3 patients had evidence of preceding acute type B hepatitis. The diagnosis was confirmed by biopsy in 7 cases, by selective arteriography of the kidneys showing multiple small aneurysms in one case; in 2 patients the diagnosis was based upon the clinical findings only. Complete remission was achieved in 7 of 10 treated patients, in 5 patients with corticosteroids alone and in 2 patients with a combination of corticosteroids and cytotoxic agents. 4 patients died, one of them from vasculitis and 3 from other causes. 5-year survival for all patients was 52%. The diagnostic value of arteriography, the clinical picture of polyarteritis nodosa with peripheral arterial occlusive disease, and the association between hepatitis B infection and polyarteritis nodosa are discussed. PMID- 2879348 TI - [Hypothesis of the purinergic nerve]. PMID- 2879349 TI - [Enzymic degradation of luteinizing hormone-releasing hormone]. PMID- 2879350 TI - [Advances in neurobiological research on the spinal dorsal horn]. PMID- 2879351 TI - [Role of the caudate nucleus in acupuncture analgesia]. PMID- 2879352 TI - Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. AB - The occurrence of seizure activity in human temporal lobe epilepsy or status epilepticus is often associated with a characteristic pattern of cell loss in the hippocampus. An experimental model that replicates this pattern of damage in normal animals by electrical stimulation of the afferent pathway to the hippocampus was developed to study changes in structure and function that occur as a result of repetitive seizures. Hippocampal granule cell seizure activity caused a persistent loss of recurrent inhibition and irreversibly damaged adjacent interneurons. Immunocytochemical staining revealed unexpectedly that gamma-aminobutyric acid (GABA)-containing neurons, thought to mediate inhibition in this region and predicted to be damaged by seizures, had survived. In contrast, there was a nearly complete loss of adjacent somatostatin-containing interneurons and mossy cells that may normally activate inhibitory neurons. These results suggest that the seizure-induced loss of a basket cell-activating system, rather than a loss of inhibitory basket cells themselves, may cause disinhibition and thereby play a role in the pathophysiology and pathology of the epileptic state. PMID- 2879353 TI - A new wave of enzymes for cleaving prohormones. PMID- 2879354 TI - Biological issues in schizophrenia. PMID- 2879357 TI - [Detoxification in benzodiazepine dependency]. PMID- 2879355 TI - Brain barrier tissues: end organs for atriopeptins. AB - Little is known about the pathophysiology of cerebral edema and other disturbances of water balance that involve the barrier tissues at the interface of blood and brain. The present experiments show that these barrier tissues contain receptors and second messenger systems for atriopeptins, recently identified cardiac peptides involved in peripheral water regulation. They also show that atriopeptins can alter the rate of cerebrospinal fluid production. Because the blood-brain and blood-cerebrospinal fluid barriers are involved in normal water movements in the central nervous system, these studies suggest that brain barrier tissues may be important end organs for the atriopeptins and that atriopeptins could have therapeutic application to disorders of water balance in the central nervous system. An isolated, purified population of atriopeptin receptor cells, obtained from choroid epithelium, was used in these experiments. This cell population may provide a valuable model system for investigating the intracellular biochemical mechanisms through which atriopeptins exert their actions. PMID- 2879356 TI - Relationship of classification to biologic behavior of non-Hodgkin's lymphomas. AB - The classification of non-Hodgkin's lymphomas (NHLs) is an important factor in treatment. Most clinical protocols divide these tumors into two broad categories- indolent, or low-grade, and aggressive, or high-grade. Patients with low-grade NHLs usually have a relatively long survival, with or without the use of aggressive therapy. Although the tumors can be controlled with conventional chemotherapeutic approaches, they are rarely cured. Patients with high-grade tumors usually die within 1 to 2 years without therapy. However, with aggressive treatment, many patients can be cured if complete remissions can be sustained for at least 2 years. Several types of NHLs represent distinct clinicopathologic entities--lymphoblastic lymphoma, adult T cell leukemia/lymphoma, true histiocytic lymphoma, Burkitt's lymphoma, and hairy cell leukemia. Immunologic concepts are now used to classify NHLs. Identifying the cell of origin of a malignant lymphoma has important therapeutic implications, since malignant cells retain phenotypic and functional properties of their precursors. It is possible, therefore, to predict both the sites of involvement and the patterns of dissemination. Clinical applications are beginning to be developed. These include the use of monoclonal antibodies, monoclonal antibodies coupled to a toxin, alpha interferon, and monoclonal anti-idiotype antibodies. Human leukocyte interferon has been used experimentally to induce spontaneous regressions. Excellent results have been achieved so far only for patients with low-grade lymphomas. PMID- 2879358 TI - [Latest findings at the International Congress on AIDS in June 1986]. PMID- 2879359 TI - Mastocytosis: one year's experience. AB - The diagnosis of systemic mastocytosis without urticaria pigmentosa has been made with increasing frequency since modern methods of histamine assay have been used clinically. We examined the incidence of urticaria-angioedema and mastocytosis over a recent 12-month period. Of 490 new patients we saw, 52 had urticaria angioedema, and ten had evidence of excess histamine +/- PGD2, with at least ten mast cells per high-power field on skin biopsy. The average age was approximately 35 years; the male:female ratio was 1:4 for urticaria-angioedema and 1:2 for mastocytosis. Symptoms of mastocytosis included flushing, abdominal cramping/diarrhea, syncope, urticaria-angioedema, pruritus, and headache. Symptoms have typically been prevented by a combination of H1 and H2 antagonists, with addition of a cyclo-oxygenase inhibitor in syncopal cases. Acute hypotension has responded to epinephrine. PMID- 2879360 TI - [Activities of feldsher-midwife centers]. PMID- 2879361 TI - [Effectiveness of acupuncture and berotec aerosol in bronchial asthma]. PMID- 2879362 TI - [Immunoregulatory lymphocyte subpopulations in patients with dilated and hypertrophic cardiomyopathies]. AB - Forty patients with dilatation cardiomyopathy (DCM) and 30 patients with hypertrophic cardiomyopathy (HCM) were examined immunologically. Immunoregulatory lymphocytes (T1B) and their subpopulations (T helpers, T suppressors, natural killers--NK) were studied quantitatively and functionally. The patients with DCM showed inhibition of the number of T suppressors in part of the cases, attended by a decrease in non-specific (spontaneous) and mitogenin-induced suppressor activity, the lowering of the amount and activity of NK in the overwhelming majority of the cases. Study of the immunological characteristics in the patients with HCM did not reveal any substantial changes as compared to those in health. Immune disorders in the patients with DCM form the basis for conducting goal oriented immunocorrection. PMID- 2879363 TI - The degradation of bovine and human prothrombin by human polymorphonuclear leukocyte cathepsin G. AB - Cathepsin G, isolated from human polymorphonuclear leukocytes, was found to effect rapid and specific degradation and biological inactivation of bovine and human prothrombin in the absence of calcium ions with the formation of two peptide fragments from the N-terminal end of the molecule. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate indicated that the molecular weights of the fragments were 5,000 and 17,500. Proteolysis of prothrombin by cathepsin G was inhibited by calcium ions. Leukocyte proteinases such as cathepsin G may be responsible for haemorrhagic disorders associated with myelocytic leukaemia and septicaemia. PMID- 2879364 TI - The antithrombotic in vivo effect of eterylate and dipyridamole in experimental thrombosis in mice. PMID- 2879365 TI - Effect of di(2-ethylhexyl)phthalate (DEHP) on spermatogenesis in adult rats. AB - Oral administration of di(2-ethylhexyl)phthalate (DEHP) in doses of 250, 500, 1000 and 2000 mg/kg to adult rats for 15 days caused a significant dose dependent decrease in the sperm count of the epididymal spermatozoa. The activity of gamma glutamyl transpeptidase (gamma GT) and lactate dehydrogenase (LDH) was significantly increased in the animals of the treated groups. An increase in the activity of beta-glucuronidase and decrease in the activity of acid phosphatase was also observed at the highest dose of DEHP. The activity of sorbitol dehydrogenase (SDH) was found to be decreased in the animals exposed to 1000 and 2000 mg/kg of DEHP. These results suggest that DEHP can affect spermatogenesis by altering the activities of the enzymes responsible for the maturation of sperms. The reduced number of sperms may be responsible for the antifertilic effects of DEHP. PMID- 2879366 TI - Changes in urinary and renal tubular enzymes caused by subchronic administration of ochratoxin A in rats. AB - The activities of 5 enzymes in urine and renal tubules were measured after administration to male Wistar rats of small doses of ochratoxin A (145 micrograms/kg per day for 8-12 weeks, corresponding to 2 ppm in the feed) by intubation. These doses are in the range of natural contaminations found in food and feed. The enzymes examined were gamma-glutamyl transferase (gamma-GT), alkaline phosphatase (ALP), leucine aminopeptidase (LAP), lactate dehydrogenase (LDH), and N-acetyl-beta-D-glucosaminidase (NAG). The doses employed caused increased enzymuria and lower activities of tubular enzymes after 1 week of feeding. This suggests tubular injury. The change of the enzyme activities in the urine and in the tubules appeared in a cyclic way (degeneration and regeneration). Phenylalanine (20 ppm) partially prevented this action of ochratoxin A. The p-[14C]aminohippurate accumulation was inhibited by 60% in the second week but returned to almost normal level 6 weeks after the beginning of the treatment, suggesting an adaptation of the organism or a substitution of damaged cells. PMID- 2879367 TI - Di-isopropylfluorophosphate induced antinociception and its interactions with opioid drugs in the rat. AB - The irreversible anticholinesterase, di-isopropylfluorophosphate (DFP), was shown to be antinociceptive in the paw pressure test in rats only at doses where animals exhibited marked signs of anticholinesterase poisoning. At sub antinociceptive doses DFP potentiated the opioid drugs fentanyl and alfentanil but failed to alter morphine antinociception. These interactions differ from our previous studies using the hot plate test in mice and suggest that opioid/cholinergic interactions are species and test dependent. PMID- 2879368 TI - Metabolic changes in rat brain synaptosomes after exposure to sulfide in vivo. AB - The effects of exposure of rats to sulfide and the action of exogenous heme were studied in rat-brain synaptosomes. Exposure to sulfide impaired the respiration of synaptosomes which was reversed by heme (4 mg/kg body weight). Sodium sulfide caused partial inhibition of gamma-aminobutyric acid (GABA) and dopamine uptake, strongly inhibited veratridine-dependent release of these neurotransmitters and reduced veratridine-dependent changes in transmembrane electrical potential. Heme treatment did not reverse these changes. PMID- 2879369 TI - A new autoreactive monoclonal antibody specific for the Thy-1 antigen. AB - The present study describes the development of a new IgM monoclonal autoantibody reactive with the Thy-1 antigen. The C16-31 monoclonal antibody (mAb) was considered as autoreactive because it reacted with thymus cells of both the C3H and BALB/c strains, which were involved in the development of the antibody. The antibody was reactive with thymus cells in both immunofluorescent and cytotoxic tests. It also showed a weak immunofluorescent reactivity with peripheral T lymphocytes. The identification of the specificity detected by the C16-31 mAb as the Thy-1 antigen was based on the following criteria: C16-31 mAB displayed a preferential reactivity with Thy-1.2 bearing thymus cells, rather than with Thy 1.1 bearing thymus cells. The tissue distribution of the antigen detected by the C16-31 antibody by direct tests and by direct tests and by adsorption experiments was in accordance with that characteristic for Thy-1. It was high on brain tissue and on thymus cells, and considerably lower on peripheral T-lymphocytes. Coating of thymocytes with C16-31 antibody blocked their reactivity with other monoclonal Thy-1 antibodies. Conversely, coating of thymus cells with rabbit anti-brain serum (RABR) inhibited the binding of C16-31. The C16-31 mAb differed from the Thy-1 autoantibodies described previously in its relatively strong reactivity with brain tissue and its considerably weaker reactivity with peripheral T lymphocytes. Moreover, C16-31 mAb showed a preferential allospecificity for Thy 1.2, only in its reactivity with thymocytes. In contrast, it reacted equally well with brain tissue from either Thy-1.2 or Thy-1.1 mice. PMID- 2879371 TI - Laboratory observations on the toxicity of Swartzia madagascariensis (Leguminosae) extract to mosquito larvae. PMID- 2879372 TI - Isolation of viruses from mosquitoes of the Negev, Israel. AB - In a survey of the mosquito population of the Negev carried out between July 1982 and September 1984, over 85,000 insects belonging to 10 species were tested for the presence of viruses. They yielded 91 virus isolates in C-6/36 mosquito cell cultures; 20 of the isolates were recovered also in Vero cell cultures and in suckling mice inoculated intracerebrally. Of the 20 isolates recovered in the vertebrate systems 17 were identified as Sindbis, and three as West Nile viruses. 71 viruses which have been isolated only in mosquito cell cultures remain unidentified. Sindbis and West Nile arboviruses were isolated only from Culex pipiens and from Cx perexiguus, while the unidentified viruses were isolated from these and from five other mosquito species. PMID- 2879370 TI - Drug effects upon aqueous production. PMID- 2879373 TI - Transient hemopoietic stem cell engraftment after transplantation of HLA haploidentical, T-cell-depleted bone marrow. PMID- 2879374 TI - Correlation between tyrosine hydroxylase immunoreactive cells in tumors and urinary catecholamine output in neuroblastoma patients. AB - The results of an immunocytochemical evaluation of tyrosine hydroxylase (TH) immunoreactivity in 30 neuroblastic tumors of infancy are reported. Although no correlations could be found between the immunoreactive pattern and the site of origin or the staging of the tumor, a positive relationship between the urinary catecholamine output and the density of TH-immunoreactive cells could be established. TH was mostly localized on the cytoplasm of the differentiating neuroblasts, whereas immature elements were rarely positive. Moreover, 2 stage IVS cases did not contain any TH immunoreactivity. The possible significance of this finding in the investigation of this form of neuroblastoma, which has a peculiar biological behavior, is considered. PMID- 2879375 TI - [Treatment of disorders in the lesser circulation following closed mitral commissurotomy by the combined use of cordanum and sodium nitroprusside]. AB - The investigation of hemodynamics and gas composition of blood in 14 patients has shown that combination of cordanum and sodium nitroprusside is expedient for the improvement of hemodynamics in the postoperative period. PMID- 2879376 TI - Age-related peptide production by human thyroid C cells. An immunohistochemical study. AB - C cells of thyroid are known to express a variety of products beside calcitonin. These include the peptides PDN21 (katacalcin), calcitonin-gene related peptide (CGRP), bombesin and somatostatin. The expression of these products has been investigated by immunohistochemistry of thyroid tissue in six age ranges from fetal to late adult life. PDN 21 was found to have co-expression with calcitonin. CGRP and bombesin both demonstrated an age-related increase in numbers and intensity of cells stained. Somatostatin immunoreactivity was limited to small numbers of cells. PMID- 2879377 TI - Antral gastrin-producing G-cells and somatostatin-producing D-cells in peptic ulcer. AB - The number of G cells and D cells per area unit and the G cell/D cell ratio was studied in control subjects and patients with duodenal or gastric ulcer. A great inter-individual variation in the population density of both types of cells was observed in the three groups studied. G cell density was significantly decreased in both duodenal and gastric ulcer patients, when compared with controls; whereas no difference in G cell density was seen between duodenal ulcer patients and gastric ulcer patients. However, D cell density was significantly decreased in duodenal ulcer patients when compared with control subjects and gastric ulcer patients. In this latter group, D cell density was also lower than in control subjects. A significant positive linear correlation between G cell number and D cell number was found in the three groups studied. The G cell/D cell ratio was significantly increased in duodenal and gastric ulcer patients when compared with controls. This was mainly due to a decrease in D cell numbers. It is concluded that a local deficit in antral D cells in patients with peptic ulcer may favor the pathogenesis of ulcer disease. PMID- 2879378 TI - Immunoelectron microscopic localization of immunoglobulin in B-cell lymphomas. AB - Subcellular localization of immunoglobulin (Ig) by immunoelectron microscopy was performed on 20 B-cell lymphomas of low- and high-grade malignancy. The efficiency in demonstrating Ig by pre-embedding technique depends on the antibodies used. F(ab')2 fragments of antibodies were more sensitive than both intact polyclonal and monoclonal antibodies in detecting cytoplasmic Ig. With immunoelectron microscopy Ig could be demonstrated in all cell types of B-CLL and LP-immunocytoma, even in some of the small lymphocytes in B-CLL. Thus, the presence of intracytoplasmic Ig has no diagnostic relevance in differentiating B CLL from LP-immunocytoma. However, the amount of Ig in the tumor cells of LP immunocytoma seemed to be greater than in B-CLL. Centrocytic lymphoma and centroblastic/centrocytic lymphoma could be differentiated by their different localization of Ig. In centrocytic lymphoma Ig was localized mainly on the surface membrane, whereas in centroblastic/centrocytic lymphoma moderate amounts of Ig could be detected in the rough endoplasmic reticulum and perinuclear space of the centroblasts and in roughly one third of the centrocytes. In malignant lymphomas of high-grade malignancy (ML centroblastic, ML immunoblastic, and ML lymphoblastic) Ig was localized mainly in the rough endoplasmic reticulum and sometimes in the perinuclear space. PMID- 2879379 TI - Cinemicrographic observations of cultured adrenocortical tumor cells. Dynamic responses to ACTH and cytochalasin B. AB - ACTH increases the basal steroidogenic activity of cultured adrenocortical tumor cells, whereas moderate-high doses of cytochalasin B (CB) inhibit both basal and ACTH-induced steroidogenesis. Previous ultrastructural studies have revealed that ACTH rearranges microfilaments in these adrenal cells, whereas CB causes microfilaments to aggregate into felt-like masses. It has been postulated that the ACTH effects may facilitate organelle motility and increase organelle interactions that are required for steroid biosynthesis, and that the CB-created "foci" may impede or prevent the organelle meetings. To shed light on these possibilities, we have employed 16 mm cinemicrography of unstimulated adrenal tumor cells and cells incubated for 1-2 h with ACTH (10 mU/ml), or low (10 micrograms/ml), or high (50 micrograms/ml) doses of CB. ACTH caused initial increases in membrane ruffling and a "flurry" of particle (organelle) activity above that seen in unstimulated cells. The stimulated cells then retracted from each other and began their characteristic "rounding up" in response to the hormone. Particles appeared to move towards the nucleus, and in fully-rounded cells were extremely congested. Steroid production rose several fold above basal levels. CB10 produced slight-marked cell convexities, nearly stopped particle motility and inhibited steroid production moderately. CB50 produced an asymmetrical, spidery cell form, stopped membrane ruffling and particle motility and abolished steroidogenesis. After a washout of CB50, particle motility resumed nearly immediately. Our CB data indicate that associations between particles, presumably between mitochondria and various sources of cholesterol, are prerequisite for basal steroidogenesis in the adrenal tumor cells. In ACTH stimulated cells, increases in steroid output correspond with increased opportunities for particle associations. These opportunities appear to arise directly or indirectly from ACTH effects on microfilaments. The responses of microfilaments to the hormone may be particularly intense in tumorous forms. By these means, the cells may express their differentiated function, although their cytoplasm has a distinctly unspecialized appearance. PMID- 2879380 TI - Immunohistological patterns of non-neoplastic changes in the thymus in Myasthenia gravis. AB - Non-neoplastic thymuses from 20 patients with myasthenia gravis (MG) have been studied by routine stains on paraffin sections and by immunohistological methods on frozen sections using a panel of monoclonal antibodies against thymic epithelial cells, macrophages/reticulum cells, lymphoid cells and myoid cells. Three types of thymic histology in MG were distinguished: (1) thymitis with lymphoid follicular hyperplasia (11 cases), (2) thymitis with diffuse B-cell infiltration (5 cases) and (3) thymic atrophy (4 cases). Thymitis was more common in younger females and thymic atrophy in older patients. Both types of thymitis were associated with conspicuous structural disturbance of the thymic perivascular space (PVS) and medulla, characterized by a distinct enlargement of the PVS and disruption of the epithelium and reticulin fibre network at the medullary boundary, leading to fusion of the two compartments. The PVS and medulla contained a striking B-cell infiltration. Large well-developed germinal centers (GCs), showing the same cellular organization as in the peripheral lymphatic system, occurred in thymitis with lymphoid follicular hyperplasia, whereas thymitis with diffuse B-cell infiltration merely exhibited a few tiny lymphoid follicles, which could be demonstrated only by immunostaining of dendritic reticulum cells. In thymic atrophy a diffuse B-cell infiltration of the PVS and the medulla was also observed, but only minor alterations of the epithelial framework were seen. There was an increased number of interdigitating reticulum cells with variable expression of the T-6 antigen in all the thymuses examined, indicating an immune stimulation of the intrathymic T-cells. Myoid cells, the supposed target of the intrathymic immune reaction in MG, were found to be less frequent in thymic atrophy than in thymitis. This variable number of myoid cells may explain the different grades of immune stimulation and different types of histology seen in the thymus in MG. PMID- 2879381 TI - The suramin-treated rat as a model of mucopolysaccharidosis. Variation in the reversibility of biochemical and morphological changes among different organs. AB - We have examined the reversibility of the biochemical and pathological changes induced in the spleen, kidney and lung of the suramin-treated rat which we have previously proposed as a useful model of the human condition, mucopolysaccharidosis (MPS). Rats were injected with a single intravenous dose of suramin (250 mg/kg) and allowed to survive for periods of up to 6 months. The organs were examined for suramin content, pathological changes, biochemical storage of glycosaminoglycans (GAGs) and for the blockage of the relevant hydrolytic enzymes. The extent and rate of suramin accumulation and the retention of the drug varied considerably between organs with the greatest concentration of suramin (4,000 micrograms/g) occurring in the kidney 2 weeks after injection. Suramin persisted at gradually decreasing levels in all organs for the duration of the experiment, remaining at the highest level (1,150 micrograms/g) in the kidney. The concentration of GAGs peaked 10-18 days after administration of the drug, in all organs. Within 6 months the level had returned to normal in the liver, spleen and lung, but remained elevated in the kidney. The activities of beta-glucuronidase and acid phosphatase were decreased in all organs at diminishing levels throughout the experiment. There was a significant increase in the activity of arylsulphatase B, except in the kidney, where the predominant effect was a reduction of activity. Recovery from the morphological changes was evident in all organs except the lung within 6 months of suramin administration. The reversibility of the biochemical and pathological changes in the various tissues is discussed and compared with the earlier results described for the liver (Rees et al. 1986) and the implications of using suramin for the treatment of human trypanosomiasis, onchocerciasis and AIDS are considered. PMID- 2879382 TI - Amyloid-enhancing factor (AEF) in the pathogenesis of AA-amyloidosis in the hamster. AB - AA-amyloidosis was induced in hamsters receiving amyloid-enhancing factor (AEF) by daily subcutaneous injection with either an aged casein solution or casein supplemented with lipopolysaccharide (LPS). Both amyloid inducers gave similar results with respect to amyloid development in spleen, liver and kidneys and to serum amyloid A (SAA) concentrations and plasma cathepsin D activities. AEF was isolated from amyloid-containing tissue by the method described by Hol et al. (1985), and amyloid-enhancing material was also extracted from isolated hamster amyloid fibrils by intensive sonification. This fibril-derived amyloid-enhancing material lacked typical green birefringence after staining with Congo red and appeared as amorphous material on electron microscopy. AEF shortened the pre amyloid phase for splenic and hepatic amyloid development and also the subsequent interval before renal amyloid deposition. This indicates that endogenous AEF, unlike passively transferred preformed AEF, is not distributed throughout the body and is probably generated at the site of amyloid deposition. Moreover, these results suggest that amyloid deposition in the kidneys, like that in the spleen and liver, involves an AEF-dependent pathway. Thus redistribution of amyloid is probably not an important cause of renal amyloid involvement. In addition to the reduction in the lag phase for splenic and hepatic amyloid deposition, AEF also speeds the changes in SAA concentration and plasma cathepsin D activity. This indicates that AEF accelerates rather than eliminates the pre-amyloid phase. PMID- 2879383 TI - Electron microscopic demonstration of intermediate cells in the healthy adult human pancreas. AB - Electron microscopic findings obtained from the pancreas of a healthy 26-year-old organ donor are reported. These findings suggest for the first time that intermediate cells (i.e. cells with morphological characteristics of exocrine acinar or ductal cells as well as endocrine islet cells) are present in the normal adult pancreas. PMID- 2879384 TI - [Psychophysiological and neurological aspects of the problem of fatigue in flight personnel]. PMID- 2879385 TI - [Serum alkaline phosphatase and gamma-glutamyltranspeptidase in metastatic malignant tumors]. AB - Levels of gamma-glutamyltranspeptidase and total, alpha 2 and alpha 1-alkaline phosphatase versus dissemination pattern and survival time were studied in patients with stage III and IV tumors of various sites. No significant changes in the activity of the said enzymes were registered in cases of single hepatic metastasis and metastasis-free liver. A slight increase in the enzymes' activity was observed in patients with pronounced liver involvement within months 10-4 before death. That was followed by a sharp and marked (3-4 times normal) rise in the levels during months 4-3. Changes in enzyme activity within the terminal 12 months were described with the aid of polynoms on the basis of regression analysis. A correlation between liver mass and degree of rise in serum enzymes levels was established. PMID- 2879386 TI - [Neurohumoral system indices in the diagnosis and treatment of chronic nonspecific lung diseases with cor pulmonale]. PMID- 2879387 TI - [Pathogenicity factors of Bacteroides (a review of the literature)]. PMID- 2879388 TI - [Silent abuse]. AB - The rate of "silent abuse" is probably underestimated by the current esteem of 1:200 in the general population. Because of the criterion of "silent inconspicuousness" most of the patients concerned elude statistical records. So much the more, however, they need medical attention. It is a highly urgent problem, involving individual as well as social medicine, and carrying the risk of massive damage to health, shortening of life expectancy and loss of ability to enjoy creativity and pleasure. The presenting symptoms are mainly headache, sleep disturbances and vegetative manifestations. The (over-)medication in use consists mainly of analgesics, tranquillizers and narcotics. The etiological background is made up (usually in close interdependency) of depression, external circumstances and neurotic development as well as a distinct type of personality (to be understood as the result of interaction between genetic and psychodynamic factors). Especially, there appears a personality structure according to the present ideal picture of achievement and order. Therefore, even from the medical point of view, hardly ever to be regarded as deviant or in need of therapy. In some cases out of this constellation arises a further enhancement of the mechanisms of abuse. Among rational objective measures we can propose: Increased information of the public and further special education of medical people, especially referring to rational therapy of depression and pain without the use of analgesics, furthermore, rational psychotherapeutic guidance; attempts at more specified and follow-up care of disaccustomed abusers; intensified public relation work in cooperation between medical doctors and politicians.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879389 TI - [Effect of celiprolol and metoprolol on serum lipids in patients with various forms of hyperlipoproteinemia]. AB - In a single-blind prospective study, patients with hyperlipoproteinemias of the types II a, II b or IV were examined for changes of their serum lipid levels under the treatment with 300 mg celiprolol or 200 mg metoprolol, respectively, for a period of 4 weeks. Celiprolol led to a reduction of serum triglycerides, while the total cholesterol level remained practically unchanged; the HDL cholesterol level rose from an average of 41.7 to 53.9 mg/dl (p less than or equal to 0.05). There was a slight increase of the LDL-cholesterol level and a significant decrease of the quotients between LDL- and HDL-cholesterol and between total cholesterol and HDL-cholesterol. Metoprolol caused a slight increase of the serum triglycerides, the total cholesterol level remained unchanged, while the HDL-cholesterol level slightly increased from 56.7 to 59.3 mg/dl. The level of LDL-cholesterol and the quotient between LDL-cholesterol and HDL-cholesterol decreased slightly. On the contrary, the quotient between total cholesterol and HDL-cholesterol remained practically unchanged. Celiprolol had a favourable influence on the serum lipid pattern, as far as the atherogenic risk is concerned. PMID- 2879390 TI - The metabolic fate of camazepam in rats. AB - The metabolites of camazepam in rat plasma were characterized by t.l.c., mass spectroscopy and n.m.r. spectroscopy as the mono- or di-desmethylated metabolites and the mono- or di-hydroxymethylated metabolites. The postulated metabolic pathways of camazepam involved stepwise series of desmethylations. The mono- and di-hydroxymethylated metabolites were found to be intermediates in desmethylation. Temazepam and oxazepam, metabolites of camazepam, were formed from the mono- or di-hydroxymethylated metabolites. PMID- 2879392 TI - Mode of action of nitrates with regard to vasodilatation and tolerance. AB - Nitrovasodilators relax vascular smooth muscle by one common mechanism, the activation of soluble guanylate cyclase leading to increased formation of cGMP. The considerable differences in potency between various nitrovasodilators appear, at least in part, to be due to the different pathways of their transformation into activators of guanylate cyclase such as nitrous oxide or nitrosothiol. Major differences were also found in the ability of these compounds to induce tolerance in isolated bovine coronary artery strips. Although the mechanism of tolerance development is still not clarified, it appears likely that cysteine deficiency may be responsible for this phenomenon since this thiol appears to be required for the transformation of certain nitrovasodilators (e.g. nitroglycerin) into stimulators of guanylate cyclase and also in the final step of activation of this enzyme. PMID- 2879391 TI - [Thiol-dependent activation of guanylate cyclase by organic nitrates]. AB - Organic nitrates produce their pharmacological effect by an intracellular stimulation of the enzyme guanylate cyclase (E. C. 4.6.1.2). We could show that the stimulatory effect of organic nitrates on the activity of guanylate cyclase is strongly dependent on the number of nitrate residues per molecule. The EC50 values found for the tetra-, tri- di-, and mononitrates differed from each other by the factor 4. In contrast to investigations carried out with the perfused isolated Langendorff heart there was no correlation between the lipophilicity of these substances and the EC50 in our guanylate cyclase preparation, as penetration of cell membranes is not required. Other authors have found that organic nitrates are able to activate the enzyme guanylate cyclase only in the presence of cysteine. There is general agreement in the literature that organic nitrates have to be cleaved before they become biologically active. During the transformation which takes place in the presence of cysteine or by means of enzymatic catalysis the nitric oxide radical is liberated as the essential stimulatory agent. We found a strict correlation between the liberation of nitric oxide from different organic nitrates (GTN, IMDN, IIDN, ISDN, IS-2-N, IS-5-N) and the degree of enzyme activation. The Ec50 values of the organic nitrates were calculated from the concentration response curves which were obtained with a guanylate cyclase preparation from rat liver in the presence of cysteine. The degradation of the organic nitrates was measured under the same conditions by means of HPLC. The amount of nitric oxide set free was calculated by using the velocity constants k of organic nitrate degradation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879393 TI - [In vitro study of the non-adrenergic non-cholinergic innervation of the rat and cat stomach]. PMID- 2879394 TI - [Hormonal control of Sertoli cell function: effect of FSH, neurotransmitters and glucagon]. PMID- 2879395 TI - [Changes in pharmacokinetics in aging and ways of correcting]. PMID- 2879396 TI - [Monoclonal antibodies in the evaluation of subpopulations of immunoregulatory T cells in patients with atopic dermatitis]. PMID- 2879397 TI - [Comparative evaluation of parameters of human oculomotor responses in a state of fatigue and in the presence of local brain lesions]. AB - Difference between saccades of the right and left eyes (saccades asymmetry) was studied in man in the state of fatigue and following local brain lesions. It has been found that external and internal influences disturbing the brain blood supply evoke an asymmetry of oculogram signals, expressed in their divergence in phase, form and amplitude. A common asymmetry coefficient has been found, which points to already existent or beginning pathological shifts of the psychophysiological state. PMID- 2879399 TI - [Study of cortical neurons by the iontophoretic method controlled by neuronal activity]. PMID- 2879398 TI - [Effect of neurohypophyseal peptides on the formation of a conditioned feeding reflex in the rat]. AB - The influence of intraperitoneal injection of vasopressin (LVP), oxytocin (OXY) and their fragments (DGAVP, PLG) on the acquisition and extinction of conditioned food reflex was studied in rats. It was found that vasopressin and its fragments had a more pronounced specific effect on the higher nervous activity of the animals. This effect consisted in impairment of the performance of the conditioned food reflex while oxytocin had a tendency to improve its performance. On the ground of the obtained data it is suggested that administration of vasopressin may facilitate the memory function only under specific environmental conditions. PMID- 2879400 TI - Opsonin independent interaction of Klebsiella strains with human polymorphonuclear leukocytes. AB - Nine encapsulated Klebsiella strains with different types of fimbriation and their nonencapsulated mutants were tested for their stimulatory potency for human polymorphonuclear leukocytes in the absence of opsonins. The luminol chemiluminescence assay was used for these experiments. It could be shown that the interaction between Klebsiella bacteria and human leukocytes is rather complex depending not only on the presence of capsules but also on the hydrophobicity of Klebsiella surface and on the type of fimbriation existing. PMID- 2879401 TI - [Reactogenic properties of a DTP vaccine with a reduced antigen dosage]. AB - The reactogenic properties of batches of adsorbed DPT vaccine with the normal content of antigens and with the content of diphtheria and tetanus toxoids reduced, respectively, to 10 Lf and 5 BU per immunization dose have been studied under the conditions of a controlled epidemiological trial. The reduced antigenic content of adsorbed DPT vaccine decreased the number of vaccinal reactions 1.8 times, as well as the intensity of their manifestations. PMID- 2879402 TI - [Comparative immunologic effectiveness of variants of the DTP vaccine]. AB - The immunological effectiveness of two batches of adsorbed DPT vaccine, the batch with the normal content of antigens (control) and the batch with the content of diphtheria and tetanus toxoids reduced to 20 Lf/ml and 5 BU/ml respectively (test batch), has been studied under the conditions of controlled trial. As a result, the reduction of the antigenic content of adsorbed DPT vaccine has been found to exert no negative influence on the immunological effectiveness of the diphtheria, tetanus, and pertussis components of this preparation under the conditions of the new immunization schedule. PMID- 2879403 TI - [Immune response to various antigenic preparations of Bordetella pertussis in whooping cough patients and convalescents studied by immunoenzyme analysis]. AB - The content of antibodies to B. pertussis disintegrated cells, protein fraction and lipopolysaccharide in the blood of patients and convalescents has been studied. The study has revealed that in the blood sera of whooping cough patients the titers of antibodies to lipopolysaccharide considerably exceed the titers of antibodies to other antigenic fractions. The titers of IgM to lipopolysaccharide have been shown to exceed the titers of IgM to other fractions 1.5-2 times. PMID- 2879404 TI - [The epidemic process of diphtheria and pertussis with active immunization of a pediatric population]. AB - The heterogeneity of humans in their immune response to the components of adsorbed DPT vaccine is shown. Improvements in the organizational forms of immunoprophylaxis are necessitated. PMID- 2879405 TI - Effect of C-protein and LC-light chains on actomyosin ATPase at various ionic strength and calcium levels. AB - Interrelation between the effects of C-protein and LC2-light chains on actin activated ATPase activity of skeletal muscle myosin has been investigated at various ionic strength (0.06-0.14) and free calcium levels (10(-4) M, 10(-8) M). The ATPase activity of AM reconstituted with column-purified myosin or partly purified myosin and non-regulated actin exhibits a pronounced dependence on ionic strength with maximum at I = 0.1. C-protein impurities (5 per cent) usually present in Minit can inhibit AM ATPase at every ionic strength assayed, without changing the character of this dependence. Actin-activated ATPase of the above myosins shows calcium sensitivity at every ionic strength studied. The partial removal of LC2 from Mcol results in a decrease of AM ATPase and in a disappearance of its calcium sensitivity. C-protein added to Mcol in a molar ratio of 1:1 inhibits considerably AM ATPase, reduces its sensitivity to ionic strength and abolishes its calcium sensitivity. PMID- 2879406 TI - Thiazinamium--induced oesophageal ulcerations. PMID- 2879407 TI - Attempts for light microscopical demonstration of guanylate cyclase activity in rat cerebellum. AB - Guanylate cyclase in rat cerebellum was investigated on the light microscopical level with guanylyl imidodiphosphate as substrate. Several attempts for activation of enzymatic activity and delimitation to other enzymes were made by sodium azide, aminophylline, sodium fluoride and dithioerythrole. The localization was similar but less strong compared to adenylate cyclase (Poeggel and Luppa 1984) and differs in behaviour to the above mentioned substances. Nucleotide pyrophosphatases seem to play an unimportant role in guanylyl imidodiphosphate conversion, while alkaline phosphatase is possibly of more importance. A light microscopical demonstration of guanylate cyclase by its enzymatic activity must be considered with caution. Main reasons are the low activity and therefore the great importance of interfering enzymes with high activities. PMID- 2879409 TI - Evidence of an estrogen-like effect of dehydroepiandrosterone on lysyl oxidase activity in the mouse cervix. AB - The effect of dehydroepiandrosterone (DHA) on the lysyl oxidase activity in the mouse cervix was studied. Injection of animals ovariectomized 10 days before with 1 mg DHA was followed 24 h later by an increase in enzyme activity, which remained unaltered for 48 h, returning to control values by 96 h after injection. At least 100 micrograms of DHA was required to increase enzyme activity; the maximum effect occurred with 1 mg of the steroid and was comparable to that of 1 microgram estradiol-17 beta. These results demonstrate an estrogen-like effect of DHA on lysyl oxidase activity in mouse cervix. The onset of response was later and the duration of response was longer for DHA than for estradiol-17 beta. PMID- 2879408 TI - Comparative hydrolase cytochemistry of the mature guinea-pig and marmoset yolk sac with special reference to proteases. AB - Proteases and gamma-glutamyl transferase linked to plasma membranes, lysosomes and secretion granules were investigated cytochemically together with phosphatases, glycosidases and non-specific esterases in the mature guinea-pig and marmoset yolk sac. Species-independently, the yolk sac epithelial cells showed high activities of lysosomal proteases, glycosidases and non-specific esterases and phosphatases, whereas species-dependent patterns were found for plasma membrane proteases, gamma-glutamyl transferase and phosphatases. Furthermore, the guinea-pig yolk sac epithelium showed marked regional differences and that of both species intercellular differences, which allowed the subdivision of yolk sac epithelial cells in various types. The high activities of all lysosomal enzymes suggests their general importance for the yolk sac function in guinea-pigs and marmosets. The different equipment of the plasma membrane with proteases, gamma-glutamyl transferase and phosphatases indicates a more species specific physiological role of this part of the yolk sac epithelial cells. PMID- 2879410 TI - Cholinergic and dopaminergic alterations in the mouse central nervous system following acute trimethyltin exposure. AB - Male mice were given a single oral dose of 0, 1 or 3 mg/kg TMT-hydroxide and sacrificed 48 hrs, 1 and 2 weeks later. Brain areas were removed, dissected and frozen for later analysis of neurotransmitter receptor binding by filtration techniques and determination of concentrations of monoamines and their metabolites by HPLC/EC. Muscarinic cholinergic receptor binding was measured over a [3H]-quinuclidinyl benzilate (QNB) concentration range of 0.02 to 2.0 nM. Two days after TMT treatment, affinity of [3H]-QNB binding in frontal cortex increased. Gradual return to control binding affinity was seen over the next 2 weeks. The number of receptors decreased only at high dose after 1 week. In hippocampus, a similar increase was seen only at the 3 mg/kg dose after 1 and 2 weeks. Homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were significantly decreased in the caudate nucleus 2 weeks after TMT treatment; concentrations of serotonin (5-HT), dopamine (DA), and 3,4 dihydroxyphenylacetic acid (DOPAC) were unaltered, nor was there a change in dopamine receptors as measured by [3H]-spiroperidol binding in the caudate nucleus or frontal cortex. To determine if TMT altered monoamine turnover or metabolite efflux, mice were dosed with 0 or 3 mg/kg TMT; 2 weeks later, pargyline (75 mg/kg, intraperitoneally) was administered and the mice sacrificed 0, 30 and 60 min. later. Monoamines and their metabolites were measured in caudate nucleus. The HVA elimination rate was unchanged. The data suggests that the lower concentrations of dopamine metabolites observed 2 weeks after TMT treatment were due to a decrease in dopamine turnover. The decrease in muscarinic receptor affinity in frontal cortex and hippocampus and the decrease in the rate of dopamine turnover in the caudate nucleus indicate that these 2 systems are affected by TMT and may participate in the expression of its toxicity. PMID- 2879411 TI - Guanine nucleotides regulate both agonist and antagonist binding to cod brain alpha 1-adrenoceptors. AB - The effect of guanine nucleotides on the binding of 3H-prazosin and its displacement by various agonists and antagonists were studied in membranes prepared from the cod brain. When cod brain membranes were maintained in a buffer containing 8 mM Mg2+, GTP (1 mM) was found to increase the specific binding of 3H prazosin Computer modelling 3H-prazosin saturation curves, suggested that the number of binding sites for 3H-prazosin was increased by 18 +/- 5% by GTP without affecting the affinity for 3H-prazosin (dissociation constant, Kd, 56 +/- 3 pM). Displacement of 3H-prazosin by adrenaline produced shallow displacement curves. Computer modelling these curves suggested that adrenaline bound to two sites - one high and one low affinity site - the Kd's being 0.14 +/- 0.03 (KH) and 7.6 +/ 0.5 microM (KL), respectively. When 1 mM GTP was present the displacement curves were shifted to the right and became steeper. Computer modelling these curves suggested that adrenaline now bound to only one low affinity site with a Kd of 7.6 +/- 0.5 microM. When unlabelled prazosin was used to displace 3H-prazosin the displacement curves were uniphasic and steep, irrespective of whether GTP was present or not. Computer modelling these curves suggested that prazosin bound to only one site with a Kd of 68 +/- 11 pM. In the absence of Mg2+ and in the presence of EDTA (0.8 mM) the displacement curve of adrenaline became steeper and the effect of GTP was almost abolished. During these conditions the ability of GTP to enhance 3H-prazosin binding was also abolished.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879412 TI - Further studies of the mechanism behind scopolamine-induced reversal of antistereotypic and cataleptogenic effects of neuroleptics in rats. AB - Scopolamine is known to attenuate the amphetamine antagonistic and cataleptogenic effect of selective DA D-2 antagonists. To study further the influence of other receptor systems three approaches were taken: concomitant treatment with receptor blockers (scopolamine, prazosin and ketanserin) and a selective D-2 antagonist YM 09151-2, testing of a neuroleptic droperidol, with mixed D-2, alpha 1 and 5-HT2 antagonistic properties and testing a selective D-1 antagonist SCH 23390. Scopolamine markedly attenuated both effects of YM 09151-2 and droperidol. In contrast neither prazosin nor ketanserin influenced the effects of YM 09151-2. Furthermore, prazosin did not influence the interaction between scopolamine and YM 09151-2 in the tests of stereotypy and catalepsy. Scopolamine did not change the amphetamine antagonistic potency of SCH 23390, but decreased moderately its cataleptogenic potency. It is concluded that 5-HT2 and alpha 1-adrenergic receptor blockade are of minor importance in order to determine the sensitivity of a DA D-2 antagonist to the reversal induced by scopolamine. Thus, our earlier hypothesis, that DA D-1 receptor blockade is the main mechanism stabilizing these neuroleptic effects against scopolamine reversal, are further supported by the present experiments. PMID- 2879413 TI - Comparison of the effects of leaving needle, direct current electrical acupuncture, and low-frequency electrical acupuncture therapy. AB - During a 3 year period from 1978 to 1980, one hundred and seventeen patients who came to the Pain Clinic of the Department of Anesthesiology of the Osaka Medical College complaining of pain, were treated with leaving needle(LN), direct current electrical acupuncture (EAP), or low-frequency electrical acupuncture(LFEA). The immediate effects of these therapies were investigated in a period of 3 days after treatment, on the basis of the patient's subjective evaluation of his relief from pain on a scale of 10 before treatment. Appearance patterns of therapeutic effects of these therapies were divided into four types: persistent (therapeutic effects persist during the 3 day period immediately after treatment), downward (therapeutic effects gradually decrease immediately after treatment), upward (therapeutic effects gradually appear after treatment), and unaltered (therapeutic effects were fair or poor during the 3 days after treatment). In addition, it was seen that of the three therapies LFEA was the best one in producing a persistent therapeutic effect and a good rate of effectiveness in the first day immediately after treatment. PMID- 2879414 TI - Electrical stimulation of the celiac plexus for pain relief in chronic pancreatitis. A clinical note. AB - A patient with intractable abdominal pain due to chronic pancreatitis was successfully treated by direct electrical stimulation of the celiac plexus. The details of the procedure are presented. This simple innocuous technique could be of value in treating patients with pain due to chronic pancreatitis who would otherwise have a near normal life expectancy. Also, it can be used in patients suffering from cancer of the pancreas and upper abdominal viscera. PMID- 2879415 TI - Comparison between transcutaneous nerve stimulation analgesic effect and electroacupuncture analgesic effect in rabbits. AB - To compare Transcutaneous Nerve Stimulation Analgesia (TNSA) with Electroacupuncture Analgesia (AA), we observed their effect and mechanism parallelly. The results are as follows: 1. Both TNSA and AA can produce significant current-dependent analgesia. The latency of AA is shorter than that of TNSA. 2. Under the present condition (lower-frequency, lower-intensity) naloxone can antagonize partly AA but not TNSA. 3. TNSA effect could be blocked partly by deep or intradermal injection of procaine into points. However, AA effect could be almost blocked completely by deep injection and not by intradermal injection of procaine. PMID- 2879416 TI - Electro-magnetic resonance phenomenon as a possible mechanism related to the "bi digital o-ring test molecular identification and localization method". AB - The author hypothesizes that the mechanism of the "Bi-Digital O-Ring Test Molecular Identification and Localization Method" is due to an electro-magnetic wave resonance phenomenon between two identical substances having an identical resonance frequency and separated by a known distance. Such a hypothesis was tested and proved by using two identical sets of electro-magnetic resonance circuits, each consisting of a fixed inductance (L) and variable capacitance (C), in place of two identical substances or molecules. When one of the resonance circuits was connected or placed close to the body surface and when the frequency of the other resonance circuit was made identical to the one placed next to the body, a maximal weakening response of the "Bi-Digital O-Ring Test" was observed only when the axes of the coils of the two separate sets of resonance circuits were oriented perpendicular to each other; when the axes of the coils of the two separate sets of resonance circuits were oriented parallel to each other, no "Bi Digital O-Ring Test" weakening response was observed, even when both resonance circuits had an identical resonance frequency. The information about the molecular structure and quantity of any molecule is contained in the specific electro-magnetic field emitted by the particular molecule. These electro-magnetic waves, containing information about the particular substance, can be propagated through a metal wire, through a "concentrated electro-magnetic field projector," or through a light beam with wavelength longer than green color (particularly a monochromatic, collimated light beam or soft laser beam). In the cases in which a light beam is used, the monochromatic light beam (including laser beam) acts as a very high frequency carrier of the electro-magnetic waves emitted from a particular substance placed near the source of the light beam or near the end of the light beam, and information on the molecular structure and amount of the substance is carried by the light beam (including laser beam) in both forward and backward directions (bi-directional propagation of information). Even reflected light from any molecule or substance in the visual field that reaches the eyes carries information on the substance to the eye ground, particularly when the individual is gazing at the substance; simultaneously, information on a substance not normally existing in the body that happens to be in the body is sent out from the eye ground in electro-magnetic waves to the object being gazed at by the individual. PMID- 2879417 TI - Sacral acupuncture for pain relief in labour: initial clinical experience in Nigerian women. AB - Sacral acupuncture was used for pain relief during labour in 30 pregnant Nigerian women. It produced clinically adequate analgesia in 19 women (63.3%). 6 women in this group (31.6%) reported that they had experienced no pain whatsoever throughout the period of labour and delivery (average duration - 8 hours). 11 women (36.7%) had no pain relief and required pethidine injection when sacral acupuncture proved ineffective. 24 women (80%), including 5 who did not obtain relief, indicated their wish to have sacral acupuncture during their next confinement. 2 women (6.7%) objected to needling, 3 considered acupuncture useless while another 2 did not believe in it. The patients' cardio-respiratory functions and uterine contractions were not adversely affected. There were no untoward effects on the mothers or their neonates. The procedure was technically simple, the equipment light and cheap. The needles did not interfere with nursing or obstetric manouvres. The procedure was however time consuming. The results were inconsistent and unpredictable. Despite these limitations, the simplicity, cheapness and absence of physiological complications associated with the procedure, make it a worthwhile medical armament for pain relief in the Nigerian environment, with limited resources and specialized manpower. PMID- 2879418 TI - TENS treatment at home: dependence of the efficacy on frequency of use. AB - The papers of various authors on the efficacy of TENS (transcutaneous electric nerve stimulation) prompted an investigation to determine whether non-responders were in fact using the TENS equipment provided for home use correctly and for adequate periods. The principal factor in deciding on the investigation was the observation that when patients returned the equipment--because they failed to benefit--after having had it at home for a month or two, hardly any of the consumable material supplied had been used. In order to evaluate this observation quantitatively, TEN stimulators were handed out fitted with timing devices that clocked up the hours of operation. Of a total of 151 patients investigated, 86 responded to TENS after regular use for several months. The remaining 65 patients failed to obtain adequate relief. An analysis of the meter records showed that only ten patients of this group had used TENS on a regular basis. Consideration should be given to means of improving patient compliance in the future. PMID- 2879419 TI - "Bi-digital o-ring test molecular identification and localization method" and its application in imaging of internal organs and malignant tumors as well as identification and localization of neurotransmitters and micro-organisms--Part 1. AB - Using the "Bi-Digital O-Ring Test Molecular Identification and Localization Method," one can identify and localize minute amounts of bioactive substances (including neurotransmitters), micro-organisms, toxic substances, or drugs, and, in addition, one can non-invasively image normal organs as well as screen for and image the distribution of specific types of cancer of specific internal organs without using any expensive instrumentation. One can also use this method to perform a qualitative analysis of neurotransmitters, neuromodulators, and hormones on different parts of the imaged organs. The molecule or substance being investigated is compared with a minute amount of a pure control reference substance, and if the substance identical to the control reference substance exists, then the electro-magnetic waves emitted by the identical substance will produce an electro-magnetic resonance phenomenon with the electro-magnetic waves of identical resonance frequency emitted by the control reference substance, and this resonance phenomenon is hypothesized to be the basis of the "Bi-Digital O Ring Test Molecular Identification and Localization Method." The following substances have been used as control reference substances to identify and localize identical substances in vitro and in vivo: pure neurotransmitters (e.g. serotonin, beta-endorphin, methionine-enkephalin, norepinephrine, dopamine, L dopa, substance P, etc.), as well as L-tryptophan and L-tyrosine; cholesterol; steroid hormones (including aldosterone, corticosterone, cortisol, progesterone, testosterone, etc.); peptide hormones; microscopic slides of normal organs; microscopic slides of specific cancer cells of specific organs (e.g. adenocarcinoma of the head of the pancreas, adenocarcinoma of the descending colon, etc.); microscopic slides of pure micro-organisms; toxic substances (e.g. lead, mercury, KCN); drugs (including non-steroidal anti-inflammatory drugs, antibiotics, beta-blockers, calcium channel blockers, etc.); and antibodies against specific substances or micro-organisms. An intensive network of serotonin and L-tryptophan was discovered, by using the "Bi-Digital O-Ring Test Molecular Identification and Localization Method," in different parts of the body. In general, in painful areas, frequently serotonin is markedly reduced, L-tryptophan is markedly increased, and substance P is markedly increased, while in non painful areas, serotonin is markedly increased, L-tryptophan is markedly decreased, and substance P is markedly decreased.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2879420 TI - Effect of severely alkali-treated casein on gastrointestinal transit and selected intestinal enzyme activities. AB - Alkaline treatment of proteins leads to chemical changes which alter the proteins' digestibility. Severely alkali-treated casein (0.2N NaOH, 80 degrees C, 1 hour) in the diet reduces food intake and growth of young but not of adult Sprague Dawley rats. Gastrointestinal transit time is not reduced significantly in either young or adult rats. Food intake and growth rate are improved by amino acid supplementation. In this case, protein content and total leucine aminopeptidase activity are increased in the distal part of the small intestine whereas gamma-glutamyl-transpeptidase and maltase activities are increased in both the proximal and distal parts. Alkaline phosphatase activity remains unchanged. These intestinal adaptations differ from those observed in rats receiving a diet containing untreated casein and graded levels of a synthetic trypsin inhibitor. In the latter, protein digestibility remains high, gamma glutamyltranspeptidase and also maltase activities are increased in the proximal and medial parts of the small intestine only. Intestinal adaptation in rats receiving alkali-treated casein does not result from a deficiency of pancreatic proteases activity. Ileal accumulation of undigested peptides from insufficient hydrolysis of alkali-treated casein may account for these mucosal adaptations. PMID- 2879421 TI - Can central-venous replace mixed-venous oxygen saturation measurements during anesthesia? PMID- 2879422 TI - [The spectrum of hangman's fracture]. AB - The hangman's fracture is since Wood-Jones (1913) considered to be a pedicle fracture of the axial arch, combined with extensive lacerations of the intervertebral disk and the longitudinal ligaments in spine motion segment C2/3. In its mechanics it is ascribed to a non-physiological strain in the sagittal plane in particular due to added submental pressure. The various forms of strain which cause the phenomenon of the hangman's fracture are discussed in detail. In this context it appears that for the model conception chosen one must invariably also consider a rotary component. The definition of the pedicle fracture requires profound reexamination, since this topographic region manifests itself only from C3 onwards but not in the area of the axial arch. After the consideration of the location of the fracture plane the proposition is made to comply with clinical considerations instead and to define it as an intraarticular or extraarticular arch fracture. In the conclusion it is demonstrated in an exemplary manner that the monosegmental injury of the intervertebral disk and the longitudinal ligaments in the segment C2/3 considered to be typical need not be mandatory. However, if it is not present, injuries in the soft-tissue of the lower motion segments are to be expected. PMID- 2879423 TI - [First aid and transport in injuries of the spine]. AB - Prognosis of lesions of the spine and spinal cord has greatly improved in recent years. It depends significantly and decisively on early recognition of such lesions and can be improved further by on-target immediate or early measures. Especially after traffic accidents, every unconscious person must be assumed to have suffered an injury of the spine until definite proof to the contrary. Appropriate measures must therefore be taken during rescue and transportation. PMID- 2879424 TI - [Rupture of the diaphragm--a frequently undetected injury]. AB - Traumatic ruptures of the diaphragm are acquired separations of the diaphragm which are aetiologically divided into indirect and rare direct ruptures. The force required to produce indirect ruptures will usually lead to additional intraabdominal lesions of liver and spleen as well as to rib fractures and fractures at the lower extremity. Hence the sequels of these accompanying lesions are often prominent in the clinical pattern to such an extent that 50 to 70% of the diaphragmatic ruptures remain primarily unrecognised. Abdominal and/or cardiorespiratory signs and symptoms become manifest only if there is an evisceration. Hence surgical strategy in preoperatively identified diaphragmatic ruptures depends on the localisation of the rupture, on the severity of the accompanying lesions, and the time until surgical treatment can be effected. Depending on the type and severity of the accompanying lesions an average lethality of 33% must be taken into account in fresh diaphragmatic ruptures. In chronic uncomplicated eviscerations the operations lethality is about one per cent. PMID- 2879425 TI - [Treatment tactics in fractures of the midfoot]. AB - Metatarsal fractures can occur as isolated lesions in combination with injuries of the ipsilateral tarsus, or in chain injuries of the lower extremity, or within a polytrauma. The choice of surgical or conservative therapy depends significantly on localisation and dislocation of the fracture (especially the involvement of the metatarsus I or V), as well as on the extent of the primary or expected soft part damage. From 1974 to 1984, 137 patients with metatarsal fractures were treated as in patients at the Accident Hospital in Tubingen. Three groups of diseases indicated for surgery are evident from an analysis of the courses of the disease: Metatarsal fractures in combination with an ipsilateral tarsus fracture or tarsus dislocation. Metatarsal serial fracture especially in involvement of metatarsus I and/or V. Dislocated tear fracture of the base of the fifth metatarsal bone. Preference is given to percutaneous Kirschner wiring from the head of the injured metatarsal bone. The tear fracture of the base of the metatarsal bone V is treated via traction bandage. These methods are generally technically simple and enable early functional treatment and partial weight bearing. In particular, immediate surgical treatment may not only favour reposition and retention, but may also limit damage of the soft parts. PMID- 2879426 TI - [Results of functional aftercare following surgically treated ruptures of the outer ligaments. A comparative study of aftercare by a lower leg walking cast or the Dr. Spring special shoe]. AB - There is no doubt that primary suturing of the ruptured ankle ligament gives the best results regarding joint stability. However, there are differing views concerning the follow-up treatment. In particular, there are controversial opinions about the value of a special shoe by Dr. Spring during the rehabilitation phase. During the period April 1984 to July 1985 100 patients with rupture of the fibular ligament were treated operatively, 50 of whom were treated post-operatively with 14-day lying plaster of Paris followed by a further 14 days with the special shoe from Dr. Spring and 50 with a lower leg walking plaster of Paris. The results were compared over a period of 8 weeks, using objective criteria. The subjective impressions followed after at least 6 months. After 8 weeks the mobility of the joint in dorsalflexion and pronation is similar in both groups; in plantar flexion and supination better mobility was seen after the plaster of Paris treatment. There was no significant difference in the duration of unfitness for work. Subjectively, there was a reduced tendency to swelling after the plaster of Paris treatment. PMID- 2879427 TI - [Fatigue fractures in the area of the hip joint in joggers]. AB - An increased incidence of fatigue fractures of the lower extremities has been observed as a result of the jogging craze. The authors describe a fatigue fracture of the neck of the femur and a fracture dislocation (not described to date) of the hip joint with fracture of the posterior acetabular margin and avulsion of a femoral head fragment. PMID- 2879428 TI - [Indications for axis-correcting measures of the lower leg in massive malposition without adequate post-traumatic arthrosis in the knee and ankle joint]. PMID- 2879429 TI - A determinant of stature: regulation of growth hormone secretion. PMID- 2879430 TI - Cardiovascular effects of ranitidine and cimetidine during acute myocardial ischaemia in anaesthetized dogs. AB - The effects of ranitidine and cimetidine on ventricular fibrillation threshold and haemodynamics were studied in pentobarbitone-anaesthetized dogs subjected to acute coronary artery ligation. These drugs did not significantly change the ventricular fibrillation threshold nor haemodynamics before coronary artery ligation, except for remarkable haemodynamic depression by ranitidine 1 mg/kg. Ligation of the left anterior descending coronary artery reduced the ventricular fibrillation threshold, decreased systemic and left ventricular pressures and myocardial contractility, and slightly increased heart rate. Pretreatment with ranitidine 0.25 or 1 mg/kg, or with cimetidine 2 mg/kg, significantly abolished the reductions in ventricular fibrillation threshold, but did not noticeably alter the haemodynamic changes. These findings further support the hypothesis that histamine release may contribute to the increased ventricular vulnerability resulting from acute myocardial ischaemia. However, the role of histamine in the haemodynamic responses to coronary artery ligation remains obscure. PMID- 2879432 TI - Fimbriae in Escherichia coli isolated from the small intestine of piglets. PMID- 2879431 TI - Inflammatory mechanisms in the Arthus reaction. PMID- 2879433 TI - Glaucoma. PMID- 2879434 TI - Illicit drugs and the athlete. PMID- 2879435 TI - The stress of hours of work. PMID- 2879436 TI - Alpha-linolenic acid deficiency in patients on long-term gastric-tube feeding: estimation of linolenic acid and long-chain unsaturated n-3 fatty acid requirement in man. AB - Alpha-linolenic acid deficiency is described in four adults fed by gastric tube. In plasma and erythrocytes, total lipid 20:3n-9 was slightly increased but total n-6 fatty acids, arachidonic acid, and dihomo-gamma-linolenic acid were normal. Total n-3 fatty acids, 18:3n-3, 20:5n-3, 22:5n-3, and 22:6n-3 were decreased in both plasma and erythrocytes. Patients had a slight but definite scaly dermatitis, which disappeared with essential fatty acids supplementation. Simultaneously, levels of 18:3n-3, 20:5n-3, 22:5n-3, 22:6n-3, 20:3n-9, and total n-3 fatty acids became normal while 18:2n-6, 20:3n-6, 20:4n-6, and total n-6 acids were unchanged or slightly lowered. Estimated minimal daily requirement of linolenic acid and of long-chain unsaturated n-3 acids in adults is approximately 0.2-0.3% and 0.1-0.2%, respectively, of total energy intake. Results suggest that conversion of linolenic acid to 22:6n-3 is increased in linolenic acid deficiency. PMID- 2879437 TI - Lactational and clear cell changes of the breast in nonlactating, nonpregnant women. AB - Secretory changes that occurred in the breasts of 32 women who were not pregnant or lactating were reviewed. These changes took two forms, with partial or complete involvement of one or more lobules. The more frequently occurring focal lactating effect was observed in 23 patients. The second form, a marked clearing of the cytoplasm within acinar cells, occurred in nine patients. Both patterns were present simultaneously in 2 of the 32 patients. Hormonal, anti-psychotic, and anti-hypertensive medications appear to correlate with the lactational change. PMID- 2879438 TI - Further linkage data on cystic fibrosis: the Utah Study. AB - We reported earlier complete linkage between cystic fibrosis and an RFLP of the met proto-oncogene revealed by the probe pmetH. Another clone, pmetD, detects another polymorphism with the TaqI restriction enzyme. Further linkage studies, now involving 22 families, have confirmed the tight linkage of cystic fibrosis to the MET and D7S8 loci. Significant allelic association was found between CF and allelic series defined by the pmetH probe. PMID- 2879439 TI - Linkage of DNA markers to cystic fibrosis in 26 families. AB - Two DNA markers, the met oncogene and the anonymous probe, pJ3.11, previously reported to be tightly linked to cystic fibrosis (CF), were used for linkage analysis in 26 families with two or more individuals affected with CF. A new high frequency polymorphism was identified using BanI and the pmetD probe. The results of linkage analysis were as follows: between met and CF, lod score of 18.2 at theta of .009; between pJ3.11 and CF, lod score of 12.1 at theta of 0; and between met and pJ3.11, lod score of 16.7 at theta of 0. These data indicate that most or all of CF is due to an abnormality at a single locus and that the DNA markers are useful for prenatal diagnosis and heterozygote detection within affected families. PMID- 2879440 TI - A linkage study of cystic fibrosis in extended multigenerational pedigrees. AB - The linkage of polymorphic DNA markers on chromosome 7 to cystic fibrosis (CF) was examined in two pedigrees and a number of smaller nuclear families. The pedigrees are multigenerational and together consist of more than 300 members including 30 affected individuals, while the nuclear families each have two generations and either two or three children with CF. Tight linkage was observed between the CF locus and the met oncogene locus theta = 0, zeta = 15.45), pJ3.11 (theta = 0, zeta = 10.07), and 7C22 (theta = 0, zeta = 6.64) in both the pedigrees and nuclear families with no evidence for recombination between CF and any of the DNA markers. Weaker linkage between the CF locus and the locus for the serum enzyme activity marker paraoxonase (PON) was detected, theta = 0.18, zeta = 0.76. The two pedigrees were sufficiently informative to detect significant linkage between CF and each of the three DNA markers previously shown to be tightly linked to the CF locus. These results establish a locus for CF in these pedigrees in the region of chromosome 7 nearest the three DNA markers met, pJ3.11, and 7C22 and are consistent with locus homogeneity for the defect causing CF in these populations and others that have been examined to date. PMID- 2879441 TI - Isolation and characterization of DNA probes from a flow-sorted human chromosome 8 library that detect restriction fragment length polymorphism (RFLP). AB - We have used a recombinant DNA library constructed from flow-sorted human chromosome 8 as a source of single-copy human probes. These probes have been screened for restriction fragment length polymorphism (RFLP) by hybridization to Southern transfers of genomic DNA from five unrelated individuals. We have detected six RFLPs distributed among four probes after screening 741 base pairs for restriction site variation. These RFLPs all behave as codominant Mendelian alleles. Two of the probes detect rare variants, while the other two detect RFLPs with PIC values of .36 and .16. Informative probes will be useful for the construction of a linkage map for chromosome 8 and for the localization of mutant alleles to this chromosome. PMID- 2879442 TI - RFLP analysis of HLA-DR and -DQ genes and their linkage relationships in the Pacific. AB - Human genomic DNA samples from Melanesians, Micronesians, and Caucasoids of known HLA-DR type were examined with cDNA probes for HLA-DR alpha, -DR beta, -DQ alpha, and -DQ beta chain genes. DR beta hybridizations with TaqI-digested DNA did not detect any new DR specificities in the Pacific. However, within the DR5 specificity a common DNA subtype was found in Pacific Islanders that was not seen in Caucasoids. Altogether, four DNA subtypes of DR5 are described. With the DQ alpha and DQ beta probes, significantly more variation could be demonstrated between populations. For example, DR2 was associated with a DQ beta TaqI pattern in the Pacific that was very rare in Caucasoids and additional RFLP analysis with other enzymes showed that this pattern is probably associated with the Dw12 subtype of DR2. DRw8-positive samples showed two different DQ alpha TaqI patterns, and these correlated with DQw1 and DQw3 specificities. DR alpha hybridizations with BglII-digested DNA also revealed different linkage relationships of the HLA-class II region genes between Pacific and Caucasoid specimens. The different population linkage disequilibrium relationships have permitted tentative assignment of TaqI fragments to either the DR beta 1 or DR beta 2 genes and are highly suggestive that the DQw1 specificity is encoded by the DQ alpha chain gene. This study shows the value of population comparisons in contributing to knowledge of the genetic organization of the genome. PMID- 2879444 TI - Calcium antagonists and the second drug for hypertensive therapy. AB - Calcium antagonist monotherapy is more effective in older patients and in those with low plasma renin activity, whereas beta blockers control blood pressure better in younger patients and in those with normal or high renin activity. Monotherapy with a calcium antagonist has been shown to result in the reduction of diastolic blood pressure to equal to or less than 95 mm Hg in more than 80 percent of patients with essential hypertension. We investigated the antihypertensive efficacy of verapamil plus an angiotensin converting enzyme inhibitor and nifedipine plus a beta blocker in 24 patients (aged 41 to 68) with moderate to severe hypertension in whom monotherapy with a calcium antagonist had been ineffective. Blood pressure recorded in patients during the placebo period was 175 +/- 3/111 +/- 2 mm Hg (mean +/- SEM). Twelve patients received monotherapy with nifedipine (50.0 +/- 5.2 mg per day) and 12 others received verapamil (460 +/- 20 mg per day); neither treatment resulted in the reduction of diastolic blood pressure to less than 90 mm Hg. However, this goal was achieved when atenolol (89.5 +/- 25.7 mg per day) was added to the regimen of patients receiving nifedipine and enalapril (29.5 +/- 5.0 mg per day) was added to the regimen of those receiving verapamil; resultant blood pressures were 127 +/- 3/83 +/- 2 mm Hg and 137 +/- 5/85 +/- 1 mm Hg, respectively. It is suggested that in patients in whom hypertension is inadequately controlled by calcium antagonist monotherapy, counter-regulatory mechanisms can be blocked by the addition of a beta blocker or an angiotensin converting enzyme inhibitor to the calcium antagonist regimen, resulting in greatly improved, simple, well-tolerated, and safe control of blood pressure. PMID- 2879445 TI - Neuroendocrine disorders of the gastroenteropancreatic system. Clinical applications of the somatostatin analogue SMS 201-995. April 2-4, 1986, San Diego, California. PMID- 2879443 TI - Strategies in antihypertensive therapy: implications of the kidney. AB - Because we so rarely know the cause of hypertension, antihypertensive therapy remains empiric. However, certain principles of treatment are emerging; one of these concerns the critical role of the kidney in antihypertensive therapy. Whether or not the kidney is primarily responsible for hypertension in a patient, it is the patient's renal response to treatment that determines, to a major degree, an agent's efficacy. Vasodilators have been a conceptually attractive approach to the treatment of high blood pressure, because they decrease total peripheral resistance, which is considered to be the mechanism responsible for this condition in most patients. Nonspecific vasodilators exert a series of actions on the kidney--including profound sodium retention and reactive renin release--that limits therapeutic response. For reasons that are not yet clear, but are apparently related to specific action on calcium entry into vascular smooth muscle, endocrine function, and renal hemodynamics, calcium channel blocking agents, such as nifedipine, have an advantage in the treatment of hypertension. They cause little or no sodium retention; thus, the addition of a diuretic agent is not required. In fact, there is evidence that sodium loading in certain patients may potentiate the antihypertensive efficacy of these drugs. The renin-angiotensin system seems to be activated to a somewhat lesser degree by calcium channel blocking agents than it is by nonspecific vasodilators; in addition, these agents interfere with the actions of angiotensin on aldosterone release. Moreover, their dilator action on the renal blood supply favors sodium excretion. Nifedipine either has no effect on the renal blood supply or induces an increase in renal blood flow and maintains glomerular filtration rate, both of which combine to support the ensuing natriuresis. PMID- 2879446 TI - Neuroendocrine tumors. A European view. AB - A center in Belfast, Northern Ireland, has established a register for tumors of the gastroenteropancreatic endocrine system. Carcinoid tumors occur most frequently. Of the non-carcinoid tumors, insulinomas, gastrinomas, and unknown types have the highest incidence, with other types being extremely rare. The potentially remediable nature of the tumors is stressed, and frequently a good quality of life can be experienced even in the presence of metastatic disease. The syndromes are probably underdiagnosed as they present with clinical features for which there are more common explanations, and appropriate diagnostic methods are therefore not used. The management of the syndromes is reviewed with particular emphasis on the treatment of patients with inoperable disease. Histamine (H2)-receptor antagonist therapy has made an impact in Zollinger Ellison syndrome, and streptozotocin and somatostatin analogues can control tumor growth and endocrine syndromes, respectively. PMID- 2879447 TI - Somatostatin analogue (SMS 201-995) in the management of gastroenteropancreatic tumors and diarrhea syndromes. AB - SMS 201-995 (Sandostatin) was studied using low doses (50 to 100 micrograms) administered subcutaneously every 12 hours. A single 50-micrograms dose of SMS 201-995 effectively controlled gastric acid and blood gastrin levels for 12 hours in three patients with benign gastrinomas and was useful in their perioperative management. Higher doses of the agent (500 to 800 micrograms per day) had no effect on metastases in one of two patients with metastatic gastrinoma. In the other patient, one tumor shrank but the other continued to grow after three months of treatment while serum gastrin levels did not change. Cultured metastatic tumor tissue from this patient released different forms of gastrin; growth rates varied, independent of uptake of SMS 201-995, and gastrin release increased. A neonate with nesidioblastosis maintained normal blood glucose levels while receiving SMS 201-995 therapy following a 95 percent pancreatic resection. In two elderly patients with organic hypoglycemia--one with a single benign adenoma and one with multiple adenomatosis--the somatostatin analogue did not prolong the hypoglycemia-free interval. In nine patients with carcinoid syndrome, flushing was uniformly controlled with 50 micrograms of SMS 201-995 administered every eight to 12 hours. One of the nine required exocrine pancreatic replacement. After six months of treatment, three of the nine had no change in tumor size and one had remission of symptoms and stopped treatment. In two patients with vipoma, SMS 201-995 controlled diarrhea and reduced levels of vasoactive intestinal peptide; tumor necrosis occurred in one patient. In a patient with diabetic diarrhea unresponsive to all treatments, SMS 201-995 therapy controlled the diarrhea but did not interfere with control of the diabetes. PMID- 2879448 TI - Characterization of the in vivo and in vitro inhibition of gastrin secretion from gastrinoma by a somatostatin analogue (SMS 201-995). AB - Earlier experiments characterized the effect of SMS 201-995 on gastrin secretion from gastrinoma in vivo. The results showed that the somatostatin analogue inhibits basal as well as secretin- and calcium-stimulated gastrin secretion. The current study examined the effect of SMS 201-995 on gastrin secretion from gastrinoma in vitro. Gastrinoma cells were prepared in cell culture or acute cell dispersion to study basal gastrin release. In cell culture, SMS 201-995 at 10(-9) M, 10(-8) M, and 10(-7) M significantly stimulated gastrin secretion (basal medium gastrin, 157 +/- 7.9 pg/ml; with SMS 201-995 10(-9) M, 786 +/- 62 pg/ml; with SMS 201-995 10(-8) M, 569 +/- 72 pg/ml; and with SMS 201-995 10(-7) M, 258 +/- 26 pg/ml). In contrast, in acute cell dispersion, the somatostatin analogue inhibited gastrin secretion (basal medium gastrin, 12.8 +/- 1.3 ng/ml; with SMS 201-995 10(-9) M, 9.0 +/- 0.1 ng/ml; with SMS 201-995 10(-8) M, 8.4 +/- 1.5 ng/ml; and with SMS 201-995 10(-7) M, 7.9 +/- 0.2 ng/ml). Gastrinoma cells were prepared in cell culture to study the effect of SMS 201-995 on gastrin secretion stimulated by secretin and by post-receptor increases in adenosine cyclic nucleotide. The somatostatin analogue inhibited gastrin secretion stimulated by secretin (10(-6) M) (797 +/- 48 pg/ml for secretin alone, compared with 396 +/- 9.4 pg/ml for secretin plus SMS 201-995). SMS 201-995 did not inhibit gastrin secretion stimulated by dibutyryl cyclic AMP (10(-7) M) (617 +/- 62 pg/ml for dibutyryl cyclic AMP alone, compared with 778 +/- 55 pg/ml for the two together). In vitro, SMS 201-995 inhibits basal gastrin secretion from gastrinoma prepared in acute cell dispersion, but not gastrinoma in cell culture, probably due to differences in basal secretory rates. The effect in vitro is less than that in vivo. SMS 201-995 does not inhibit postreceptor increases in adenosine nucleotide. This indirectly supports the hypothesis that SMS 201-995 acts in gastrinoma cells to inhibit gastrin secretion by inhibition of adenylate cyclase activity. PMID- 2879449 TI - Comparison of the effect of somatostatin and an analogue, SMS 201-995, on gastrin and insulin secretion from isolated perfused rat stomach and pancreas. AB - The effects of a somatostatin analogue, SMS 201-995, and somatostatin-14 on gastrin and insulin release from the isolated perfused rat stomach and pancreas were studied. Equipotent effects were observed on the inhibition of basal gastrin release from the stomach. SMS 201-995 was approximately 14 times less effective than somatostatin-14 (molar basis) in the pancreas. At a high glucose concentration (17.6 mM), neither the analogue nor the peptide inhibited insulin release, but at a glucose concentration of 8.8 mM, there was significant inhibition. In the presence of 10 mM arginine plus glucose at a concentration of either 8.8 or 17.6 mM, insulin secretion was reduced by both SMS 201-995 and somatostatin-14 to levels obtained with glucose alone. However, when gastric inhibitory polypeptide (10 ng/ml) in the presence of 8.8 mM glucose was used to stimulate insulin release, somatostatin-14 completely inhibited the insulinotropic action of gastric inhibitory polypeptide while SMS 201-995 was without effect. Studies with this analogue suggest that arginine and gastric inhibitory polypeptide stimulate insulin release via different mechanisms. PMID- 2879450 TI - Somatostatin: a peptide with unexpected physiologic activities. PMID- 2879451 TI - Treatment of postprandial hypotension with a somatostatin analogue (SMS 201-995). AB - A somatostatin analogue, compound SMS 201-995, was used to treat postprandial hypotension in a patient with autonomic neuropathy. Prior to treatment, the patient's mean blood pressure decreased 50 to 80 mm Hg after each meal, resulting in frequent loss of consciousness. Subcutaneous administration of low doses of compound SMS 201-995 (12 to 16 micrograms) prevented the postprandial hypotension. The therapeutic benefits of SMS 201-995 dissipated after a few hours, however, which made it necessary to administer the drug with each meal. No adverse effects of this agent were noted over a nine-month treatment period. Compound SMS 201-995 provided safe and effective therapy for postprandial hypotension. PMID- 2879452 TI - Effects of SMS 201-995 on intermediary metabolism and endocrine status in normal and diabetic humans. AB - The hormonal and metabolic effects of the somatostatin analogue SMS 201-995 have been examined in normal and diabetic humans. When 50 micrograms of analogue was administered subcutaneously at 8 A.M. and 5:30 P.M., growth hormone secretion over 24 hours was not significantly affected, and the nocturnal growth hormone surge persisted in normal subjects and in type II diabetic patients. Insulin secretion was suppressed in both groups, but glucose tolerance deteriorated only in the normal subjects. Gastrointestinal side effects developed in both groups. Subcutaneous administration of 50 micrograms of SMS 201-995 at 11 P.M. decreased nocturnal growth hormone secretion (peak, 5 +/- 2 milliunits/liter versus 23 +/- 6 milliunits/liter; p less than 0.01) in normal subjects. Postprandial circulating glucose and insulin levels the following day were unaffected by SMS 201-995, and no side effects were observed. In type I diabetic patients receiving a variable rate insulin infusion overnight to maintain normoglycemia, SMS 201-995 (50 micrograms) administered at 11 P.M. decreased insulin requirements for two to three hours after injection. Insulin sensitivity thereafter was unaffected despite suppression of growth hormone secretion. Alternative dosage regimens are necessary to suppress growth hormone release over 24 hours and to minimize side effects in type II diabetes. Administration of the analogue in the late evening suppresses growth hormone secretion overnight, but the "dawn phenomenon" persists in type I diabetic patients. PMID- 2879454 TI - Preferences and practices of Americans and their physicians in antihypertensive therapy. AB - In the summer of 1986, the Gallup Organization conducted two surveys, one of the physicians who treat hypertension and the other of patients who were receiving medications for hypertension. Objectives were to assess current patterns of treatment and the impact of cost on treatment for hypertension. Seventy percent of the patients report being prescribed medication immediately following the diagnosis of hypertension. Diuretics are the most frequently prescribed initial medication (76 percent of physicians), followed by beta blockers (44 percent of physicians). Physicians report recent trends, however, towards more use of beta blockers and angiotensin converting enzyme inhibitors and less use of diuretics. Only 59 percent of patients have insurance that covers medication, and about one in four patients report that paying for medications or physicians' fees is "very much" or "somewhat" of a problem. The costs of care are of concern to physicians as well as to patients. PMID- 2879455 TI - Essential hypertension: cost-effective evaluation and treatment. AB - The widespread prevalence of hypertension in the United States and the enormous expense and effort associated with its treatment necessitate a cost-conscious approach to evaluation and therapy. In the past, we have devoted too many resources to testing for rare diseases suspected of causing hypertension when it has been demonstrated that secondary causes are rare. Devoting resources to the effective treatment of essential hypertension itself should be a priority, because such treatment has been shown to reduce morbidity and mortality associated with hypertension and related cardiovascular diseases. Clinical and epidemiologic studies have demonstrated that treatment for hypertension should not be initiated unless diastolic blood pressure readings are 90 mm Hg or greater on three successive office visits. Treatment should be carried out in a step-wise fashion, using a non-pharmacologic approach only in situations in which hypertension is mild, target organ disease is absent, and compliance is favorable. Diuretics should be used as step-one drug therapy in most situations, because they are effective in the majority of patients, convenient to use, easy to titrate, and comparatively inexpensive. They do not cause salt and water retention, and side effects are usually minimal. When the use of diuretics is contraindicated, beta blockers are suitable alternatives, equally effective in most respects. When beta blockers or other non-diuretic drugs are used as step one therapy and an additional drug is needed, diuretics can be used advantageously in conjunction with the step-one drug. PMID- 2879453 TI - Role of a long-acting somatostatin analogue (SMS 201-995) in the treatment of acromegaly. AB - The beneficial effect of the long-acting analogue of somatostatin SMS 201-995 in the treatment of acromegaly is described in three cases, and current published experience is reviewed. A total of 64 patients from 10 series have received the drug from one to 25 months, usually in doses of 50-150 micrograms every eight hours by subcutaneous injection. Clinical and chemical improvement was observed in the majority of subjects but normal 24-hour serum growth hormone levels were achieved in no more than 35 percent of this group and possibly less. We have found that higher doses, up to 1,500 micrograms per day, which have generally been free of side effects, are sometimes required to normalize growth hormone secretion. A reduction of up to 33 percent in pituitary tumor size has been reported in more than half of the 27 cases studied from four groups. Clinically important side effects are infrequent, but diarrhea, usually transient, occurred in about 13 percent, with frank steatorrhea in 2 to 6 percent of cases. Alteration in carbohydrate metabolism, such as transient glucose intolerance at the start of therapy in non-diabetic acromegalic patients, and increased sensitivity to insulin or oral hypoglycemic agents in diabetic acromegalic patients, is common. Overall, SMS 201-995 appears to be a valuable new agent for the treatment of acromegaly, but long-term safety needs to be established. PMID- 2879456 TI - Therapeutic choice in the treatment of hypertension. Initial treatment of newly diagnosed hypertension and secular trends in the prescribing of antihypertensive medications for Medicaid patients. AB - A "stepped-care" approach has been widely recommended for more than 10 years as an empiric method for the treatment of hypertension. This approach encourages the use of diuretics or beta blockers as initial monotherapy for hypertension. Although these and other antihypertensive regimens tested in clinical trials have substantially reduced morbidity and mortality from cerebrovascular disease, their relative effectiveness in reducing the sequelae of coronary artery disease is not as well established. These findings, coupled with the development of new drug regimens, have led to a re-examination of the stepped-care guidelines. This re examination will stimulate increased interest in the therapeutic choices made by practicing physicians, particularly because the newer drugs are more costly than the traditional treatments. To address this question, we performed two specific studies, using data bases from Michigan and Tennessee Medicaid programs. The first study analyzed prescriptions for newly diagnosed cases of essential hypertension. The second study analyzed secular trends in the prescribing of antihypertensive regimens since that time. The data suggest that in 1982 and 1983 (the time period under consideration in the first part of the study), physicians treating hypertension for Medicaid enrollees followed the stepped-care recommendations, the majority using diuretics as step-one monotherapy. The secular trend data in the second study showed a moderate decrease in the use of diuretics since 1983. There were marked increases in the use of newer antihypertensive medications such as calcium channel blockers and the angiotensin converting enzyme inhibitor captopril. Because the costs of the newer drugs are substantially higher, a shift to these drugs would significantly increase the cost of treating hypertension in this country. Prospective, controlled trials are necessary to ascertain if the increased costs of the newly developed drugs are justified by potential benefits. PMID- 2879457 TI - Disparate hemodynamic responses to mental challenge after antihypertensive therapy with beta blockers and calcium entry blockers. AB - The hemodynamic response to mental challenge was studied in 40 male outpatients with mild essential hypertension. The patients were treated randomly either with a beta adrenoreceptor blocker (oxprenolol) or with a calcium entry blocker (nitrendipine). Cardiovascular reactivity was evaluated with two different mental arithmetic tasks before and six months after treatment by continuously measuring systolic and diastolic pressure (ultrasonic Doppler device), heart rate (electrocardiography), and stoke volume (impedance cardiography). Patients in both treatment groups had equal decreases in arterial pressure and the same pressures at rest. In patients receiving calcium entry blockers, mental challenge provoked an increase in stroke volume and a decrease in total peripheral resistance similar to results in the pretreatment phase. In contrast, beta adrenoreceptor blockade reversed the hemodynamic response pattern to a distinct decrease in stroke volume (p less than or equal to 0.05) and an increase in total peripheral resistance (p less than or equal to 0.05). In addition, an attenuated heart rate response (p less than or equal to 0.01) and a larger increase in diastolic pressure (p less than or equal to 0.01) were found in the beta blocker group compared with the calcium entry blocker group. Although beta blockers and calcium blockers produce equal decreases in arterial pressure, beta blockers evoke an abnormal hemodynamic response to mental challenge, whereas calcium entry blockers preserve the physiologic reactivity pattern of the untreated state. PMID- 2879458 TI - Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room. AB - The effectiveness of nebulized anticholinergic and sympathomimetic regimens was evaluated in a double-blind study of 199 patients with acute airways obstruction. Patients were assigned to one of three treatment regimens according to a randomized schedule: 0.5 mg of ipratropium bromide, 1.25 mg of fenoterol hydrobromide, and 0.5 mg of ipratropium plus 1.25 mg of fenoterol. In 148 patients with acute exacerbations of asthma (mean one-second forced expiratory volume, 1.18 +/- 0.64 liters), all three regimens produced significant improvement in one-second forced expiratory volume (p less than 0.001). The greatest improvement followed treatment with the ipratropium-fenoterol combination (0.53 +/- 0.40 liters at 45 minutes; 0.57 +/- 0.51 liters at 90 minutes) and was significantly greater than that following either ipratropium alone (p less than 0.001) or fenoterol alone (p less than 0.05). In 51 patients with acute exacerbations of chronic obstructive pulmonary disease (mean one second forced expiratory volume, 0.67 +/- 0.29 liter), each regimen produced significant improvement in one-second forced expiratory volume at both 45 and 90 minutes (for all, p less than 0.05), but there was no significant difference among the three treatment regimens. It is concluded that, in patients with acute asthma, combination therapy with sympathomimetic and anticholinergic agents is more efficacious than either one alone. In patients with acute exacerbations of chronic obstructive pulmonary disease, although either sympathomimetic or anticholinergic therapy provides bronchodilatation, no further benefit could be demonstrated from combination therapy. PMID- 2879459 TI - Frontiers in cardiology: Alpha blockade and coronary heart disease risk reduction. Symposium, Washington, D.C., September 16, 1986. PMID- 2879460 TI - Thiazide diuretics and selective alpha blockers: comparison of use in antihypertensive therapy, including possible differences in coronary heart disease risk reduction. AB - The results of several important clinical trials have confirmed the benefits of pharmacologic treatment in patients with hypertension. However, some issues concerning this type of treatment have yet to be resolved. For example, it has not been determined whether there are differences among antihypertensive agents with respect to their effects on mortality and morbidity or whether such effects are independent of the alterations in blood pressure resulting from the use of such agents. Thiazide diuretics, the most commonly prescribed antihypertensive drugs, were the first agents proven to be effective and practical for the widespread treatment of hypertension. Alpha blockers, also commonly prescribed antihypertensive drugs, provide equally effective blood pressure control to that of the thiazides, but with a very different metabolic profile. In this article, these drugs are compared for efficacy, side-effect profiles, metabolic effects, and potential for reducing the risk of coronary heart disease. PMID- 2879461 TI - Comparison of effects on lipid metabolism of antihypertensive drugs with alpha- and beta-adrenergic antagonist properties. AB - Elevated blood cholesterol levels are a major cause of coronary heart disease. High-density lipoprotein cholesterol is regarded as a protective cholesterol fraction that is negatively associated with the incidence of coronary heart disease. Thus, the ratio of high-density lipoprotein to total cholesterol levels is an expression of the total atherogenicity--the higher the ratio, the lower the risk of coronary heart disease. There is a sharp contrast between alpha- and beta adrenergic blockers with regard to their effect on the profile of blood lipids. In most studies, alpha blockers increased high-density lipoprotein cholesterol levels and decreased serum triglyceride levels. In addition, alpha blockers generally reduce total serum cholesterol levels. On the other hand, most beta blockers reduce serum levels of high-density lipoprotein cholesterol and increase serum triglyceride levels. European clinical trials recently investigated the effects of alpha blockers and beta blockers on blood lipids in a total of 104 and 281 patients with hypertension, respectively. On the average, selective alpha blockade increased the high-density lipoprotein cholesterol:total cholesterol ratio by 11.3 percent and reduced serum triglyceride levels by 11.4 percent. In contrast, the selective and nonselective beta-adrenergic blockers atenolol, metoprolol, and propranolol reduced that ratio by 11.7 percent and increased serum triglyceride levels by 25.8 percent. This difference between alpha and beta blockers may significantly influence the risk profile of coronary heart disease and should be given strong consideration when choosing drug therapy for hypertensive patients. PMID- 2879462 TI - Evolution of the clinical management of hypertension. Emerging role of "specific" vasodilators as initial therapy. AB - The primary hemodynamic hallmark of essential hypertension is elevated systemic vascular resistance that may be affected by increased sympathetic tone, activation of the renin-angiotensin system, or structural and cellular abnormalities (e.g., those involving calcium) of the blood vessel wall. The aim of therapy, therefore, is to reduce vascular tone through the use of a specific blocker of neurohormonal mechanisms or a nonspecific vasodilator. These agents are not equally effective in all patients. In comparing these drugs, the following issues are important: pathophysiology, patient demography, mechanism of drug action, long-term efficacy, and metabolic effects. Several studies have suggested that there is a response to angiotensin converting enzyme inhibitors in young and middle-aged patients, whereas in elderly patients there may be more of a response to calcium channel blockers. Alpha 1-adrenergic blockers, however, appear to be effective in all age groups. Calcium channel blockers and alpha 1 adrenergic blockers generally are more effective in black patients than are angiotensin converting enzyme inhibitors. Neither of these agents adversely affects serum potassium, glucose, or plasma lipid levels. In fact, data suggest that alpha 1-adrenergic blockers may reduce low-density lipoprotein cholesterol and triglyceride levels and increase high-density lipoprotein cholesterol levels. Unlike alpha-adrenergic blockers and angiotensin converting enzyme inhibitors, calcium channel blockers may produce a negative inotropic effect and improved cardiac diastolic relaxation. In addition to all of these factors, it is important that the agent selected as initial antihypertensive therapy be efficacious, have a favorable side-effects profile, and have no adverse influences on other risk factors. PMID- 2879463 TI - Recent advances in beta blockade. Therapeutic implications in hypertension. Proceedings of the First International Symposium on Tertatolol, 15th June, 1985, Milano, Italy. PMID- 2879464 TI - Tertatolol does not affect biochemical markers of atherosclerosis in normo- and hyperlipidemic hypertensive patients. AB - The effects of the beta-blocker tertatolol on plasma lipids and lipoproteins were studied in two groups of 10 normolipidemic (group I) and 10 hyperlipidemic (group II) hypertensive patients, for a period of 3 months. The efficacy of tertatolol was confirmed by a reduction in heart rate (HR), and in systolic (SBP) and diastolic (DBP) blood pressure, in the supine position and after 1 min in the upright position. Triglyceride (TG) levels were increased by treatment in both groups (+20% and +22%, respectively; p less than 0.05), as were VLDL levels (+16% and +24%, respectively) although the rise in the latter was not significant. There were no significant differences in levels of HDL cholesterol (HDL-C), HDL, or apoproteins A and A1 (APO A, APO A1). Total cholesterol (TC) levels were increased by treatment in group I (+10%; p = 0.050) and decreased in group II ( 9%, not significant), LDL-C being the principal fraction involved in these changes. There were no significant differences in levels of APO B. The ratio between TC and HDL-C levels remained unchanged. Given the current state of our knowledge concerning lipid markers for atherosclerosis, these results indicate that chronic administration of tertatolol may be considered devoid of 'atherogenic' effects. PMID- 2879465 TI - Long-term experience with tertatolol in hypertension. AB - The long-term antihypertensive activity and acceptability of a new beta-blocking agent tertatolol (T) (5 mg once daily) was assessed in a 12-month (M0-M12) open study, in 110 out-patients (64 men, 46 women, mean age 53.5 +/- 1.0 years), presenting with stable placebo-resistant hypertension (HT) (95 less than or equal to diastolic blood pressure less than 130 mm Hg on 3 occasions during a 1-month placebo run-in period). To obtain normalization of blood pressure (BP), treatment was adapted as from M3, adding a combined thiazide- and potassium sparing diuretic (D) and, if necessary, the vasodilator dihydralazine (V). At M12, 93.6% of patients were controlled (supine diastolic BP less than 95 mm Hg) among whom 72.7% under T monotherapy, 16.4% under double therapy (T + D) and 4.5% under triple therapy (T + D + V). Overall variations of BP were 26.4 mm Hg for SBP (from 171.7 +/- 1.6 to 145.3 +/- 1.3 mm Hg; p less than 0.01) and 19.9 mm Hg for DBP (from 105.6 +/- 0.7 to 85.7 +/- 0.6 mm Hg; p less than 0.01). Under T monotherapy, reduction in diastolic BP occurred early (15.0 mm Hg at M1) and was sustained thereafter (19.5 mm Hg at M12); HT control was comparable in the 40- to 60- and greater than 60-year-old age groups (respectively 67.6% and 74.1%) and higher in the less than 40-year-old group (100%). It also rose from 61.2% when initial diastolic BP was greater than 105 mm Hg to 82.0% when it was less than or equal to 105 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879466 TI - Acute renal effects of beta-blockers. AB - The effects on renal function of a single dose of six different beta-blockers (atenolol, propranolol, metoprolol, acebutolol, nadolol, and pindolol) have been evaluated in 51 hypertensive patients with normal glomerular filtration rate (GFR). Most drugs, except pindolol, induce a 10-20% decrease in GFR and renal plasma flow, although differences in the magnitude and the pattern of this fall are evident. The fractional excretion of sodium is generally depressed by 20-40%. These data suggest a limited renal tolerance of most beta-blockers during acute administration, irrespective of their pharmacological characteristics. PMID- 2879467 TI - Hemodynamic effects of beta-blockade in hypertension. A critical review. PMID- 2879468 TI - Renal hemodynamic effects of tertatolol compared with those of propranolol in the conscious dog. AB - Experiments were performed in which the effects of two beta-blockers, tertatolol [dl-(hydroxy-2'-t-butyl-amino-3'-propyloxy)-8-thiochroman hydrochloride] and propranolol, on mean arterial pressure (MAP), heart rate (HR), and renal function were studied in the conscious sodium-replete dog. In all experiments renal function was evaluated from the effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) assessed respectively by measurement of p-aminohippurate and creatinine clearances. These parameters were measured during two 30-min control periods, after which two further measurements were performed over a similar time period, after intravenous administration of either propranolol (0.5 mg X kg-1; n = 8) or tertatolol (0.05 mg X kg-1; n = 8), these two doses being of equivalent beta-adrenoceptor antagonist activity. Administration of propranolol and tertatolol did not change MAP but induced a significant and comparable decrease in HR. After propranolol a significant decrease in ERPF was observed, without any change in GFR or sodium excretion. In contrast, administration of tertatolol resulted in no modification of ERPF, a slight but significant increase in GFR, and a significant increase in sodium and potassium excretion. These results suggest that tertatolol and propranolol though acting similarly on systemic parameters have different effects on renal hemodynamics in the conscious dog. PMID- 2879469 TI - Role of baroreflex activation in the regional hemodynamic effects of the beta blockers tertatolol and propranolol in conscious spontaneously hypertensive rats. AB - The effects of the beta-adrenoceptor-blocking drugs tertatolol and propranolol on regional hemodynamics were compared in intact and sinoaortic denervated (SAD) conscious spontaneously hypertensive rats (SHR). Miniaturized Doppler flow probes were used for the continuous determination of changes in flows and resistances in the renal, mesenteric, and hindquarter vascular beds. In intact animals 5 mg/kg propranolol i.v. caused an initial increase and a later gradual fall in mean arterial blood pressure (MAP) and an early rise in all three resistances. In SAD rats the reduction in MAP occurred more readily and no increases in RR and MR were observed. RR even decreased significantly. 0.5 mg/kg tertatolol i.v. caused a similar change in MAP as did propranolol. In contrast, tertatolol increased resistance only in the hindquarter vascular bed, both in intact and SAD animals. These data show an important role of sinoaortic baroreflex activation in the early peripheral vasoconstriction caused by propranolol in conscious SHR. Moreover, the data suggest that tertatolol inhibits the sympathetic nervous system-mediated reflex vasoconstriction. PMID- 2879470 TI - Study of prejunctional beta-adrenoceptors in kidneys of normotensive and hypertensive rats using the new beta-adrenoceptor blocking drug tertatolol. AB - The prejunctional beta-adrenoceptors present in the isolated perfused kidney of normotensive rats (NR) and spontaneously hypertensive rats (SHR) were compared and the effects of tertatolol on these receptors were investigated. Kidneys of NR (Wistar + Wistar-Kyoto [WKY]) and SHR, were continuously perfused with Tyrode solution at constant flow and the changes in perfusion pressure were monitored. The constrictor responses to norepinephrine (2-8 X 10(-10) moles) were slightly but significantly decreased by isoproterenol (2 X 10(-7) M) to a similar degree in NR and SHR. Tertatolol (3 X 10(-7) M) did not alter the constriction caused by norepinephrine, but abolished the dilator response to isoproterenol. Electrical stimulation of renal nerves (8 Hz) evoked constrictions in both NR and SHR; these constrictor responses were augmented in the presence of isoproterenol (2 X 10(-7) M) to a similar extent in NR and SHR. In kidneys of NR and SHR, previously incubated with 3H norepinephrine, renal nerve electrical stimulation (6 Hz) evoked an overflow of the 3H transmitter. This overflow was enhanced by isoproterenol (2 X 10(-6) M) to a similar degree in NR and SHR. Both the augmented constrictor response and the augmented overflow of 3H norepinephrine caused by electrical stimulation in the presence of isoproterenol, were inhibited by tertatolol (3 X 10(-7) M). Our results show that the beta-receptor agonist isoproterenol evokes comparable effects at prejunctional beta-adrenoceptors in kidneys of NR and SHR; they also show that tertatolol is an inhibitor of pre- and postjunctional beta-adrenoceptors in the renal circulation of the rat. PMID- 2879471 TI - Tertatolol preserves renal perfusion in patients with arterial hypertension after head injury. AB - Tertatolol is a noncardioselective beta-adrenergic blocking agent without partial agonist activity. Its central and renal hemodynamic effects were compared to those of an equipotent dosage of propranolol in two groups of 10 patients each who developed arterial hypertension and a hyperdynamic circulatory state after head injury. After tertatolol, 5 mg orally, mean arterial blood pressure was unaffected, heart rate decreased by 22% (p less than 0.01) and cardiac index by 24% (p less than 0.01) while renal blood flow remained unchanged (-5%; not significant) so that the renal fraction of cardiac index was increased by 22% (p less than 0.05). After propranolol, 160 mg orally, mean arterial blood pressure was not modified, heart rate decreased by 12% (p less than 0.01), cardiac index by 16% (p less than 0.01) and renal blood flow by 17% (p less than 0.01) so that the renal fraction of cardiac index remained unchanged (-3%; not significant). Tertatolol is a potent beta-blocking agent comparable to propranolol apart from the fact that it preserves renal perfusion; this peculiar effect is related to a redistribution of the reduced cardiac output to the benefit of the kidney. PMID- 2879472 TI - Renal hemodynamic effects of tertatolol in essential hypertension. AB - Tertatolol, a new beta-blocker, and propranolol, considered a reference beta blocker, were given orally (5 and 160 mg slow release, respectively) for 15 days to two groups of patients with essential hypertension in order to compare their effects on renal hemodynamics. Systolic and diastolic blood pressure, heart rate, and erect plasma renin activity fell significantly in both groups while prostaglandin E2 urinary excretion was unchanged. Tertatolol administration produced increases in glomerular filtration rate, as shown by inulin clearance (+8.9%; p = 0.038) and renal plasma flow, as shown by paraaminohippurate clearance (+13.0%; p = 0.007). In contrast, propranolol administration resulted in a slight decrease in glomerular filtration rate (-2.8%; not significant) and a fall in renal plasma flow (-13.4%; p less than 0.001). Comparison between both treatments showed that glomerular filtration rate and renal plasma flow were higher in the patients treated with tertatolol than in those treated with propranolol whereas filtration fraction was lower, which suggests that tertatolol causes a vasodilation of the glomerular afferent arteriole. These results demonstrate that in contrast to propranolol (160 mg), and despite both drugs exhibiting a comparable antihypertensive activity, tertatolol (5 mg) does not alter but even improves renal perfusion in hypertensive patients. PMID- 2879473 TI - Antihypertensive and renal effects of tertatolol, a new beta-blocking agent, in hypertensive patients. AB - Tertatolol, a new nonselective beta-adrenoceptor blocker, was administered to 11 hypertensive patients in a short-term study. Systolic and diastolic blood pressure and heart rate were significantly decreased when compared to the placebo period: in spite of that glomerular filtration rate and renal plasma flow were unchanged. The administration of metoclopramide (a dopaminergic receptor antagonist) caused a significant reduction of renal plasma flow and a significant rise of renal vascular resistances during placebo, but no change during tertatolol therapy. A possible interference of tertatolol on dopaminergic receptors is discussed as the mechanism responsible for the unmodified renal plasma flow despite the significant blood pressure lowering with tertatolol. PMID- 2879474 TI - Effects of tertatolol in hypertensive patients with chronic renal failure. AB - Chronic renal failure (CRF) is often associated with hypertension, as a cause or a consequence. We studied the changes in blood pressure (BP), heart rate (HR), renal function (as measured by creatinine clearance), and plasma renin activity (PRA) in 19 hypertensive patients with CRF before, during and after oral administration once a day for at least 30 days of 5 mg tertatolol, a new beta blocker. All patients were free of any antihypertensive medication for at least 1 month before administration of tertatolol. The dose of tertatolol given in this study was the same as that commonly used in patients with normal renal function. From day 0 to day 30 of tertatolol, measurements in the supine position were as follows: systolic BP (SBP) decreased from 168.4 +/- 4.6 to 145.3 +/- 4.3 mm Hg (p less than 0.01); diastolic BP (DBP) decreased from 106.1 +/- 2.4 to 87.1 +/- 2.0 mm Hg (p less than 0.01); HR decreased from 77.9 +/- 1.6 to 63.2 +/- 1.7 b.p.m. (p less than 0.01); PRA decreased from 1.816 +/- 0.521 to 1.052 +/- 0.323 ng/ml/h (p less than 0.01). Creatinine clearance remained stable: 37.1 +/- 4.1 versus 37.1 +/- 4.7 ml/min/1.73 m2 (not significant). Similar results (for SBP, DBP, HR and PRA) were obtained in the erect position. It is concluded that tertatolol in hypertensive patients with CRF: significantly lowers BP and HR without excessive bradycardia, significantly lowers PRA, the most important decrease being observed for the highest initial PRA, does not alter renal function, and has a good clinical acceptability. PMID- 2879475 TI - Beta-adrenergic receptor changes during tertatolol treatment in healthy volunteers: relevance for beta-blocking therapy. AB - Tertatolol is a new potent beta-blocker without intrinsic sympathomimetic activity and lacking beta 1/beta 2 receptor subtype selectivity. Tertatolol was found in vitro to be a competitive inhibitor of beta-adrenergic receptors in competitive binding experiments. However, the density of beta-adrenergic receptors on intact human lymphocytes preincubated with tertatolol was reduced. When given at therapeutic doses (5 mg/day) to human volunteers, it induced a reduction in the number of beta-adrenergic receptors (Bmax) without any change in the affinity (KD) for intact lymphocytes (beta-adrenergic receptors were measured by the specific binding of 3H-CGP 12177). This effect was seen 7 h (-54%), 24 h ( 35%) and 48 h (-30%) after a single drug dose. A similar receptor reduction was observed 7 h (-42%), 24 h (-37%) and 48 h (-15%) after 14 daily doses of the drug. In parallel, the pharmacological efficacy of the drug was evident from the reduction in heart rate in supine and upright positions and after submaximal exercise; heart rate was reduced to the same extent after single or repeated drug doses. The reduction in receptor number correlated with the reduction in heart rate in both the supine (p less than 0.001) and upright (p less than 0.01) positions and after exercise (p less than 0.02). We conclude that tertatolol, besides competitively inhibiting beta-adrenergic receptors, induces a marked and lasting decrease in beta-adrenergic receptor number. This effect may be important for the beta-blocking effects of this drug. PMID- 2879476 TI - Choosing the right dose for beta-blocker treatment of hypertension: experience with tertatolol. AB - The determination of the optimum dosage for antihypertensive therapy, i.e. the unit dose and the administration frequency, remains one of the least discussed subjects. For beta-blockers as well as for other drugs, this determination is mainly based on the dose-effectiveness curve, the top of which corresponds to the right dose. Thus, a wide range of doses should be tested, and this as early as possible during drug development. The first step is to assess the optimum beta blocking dose in healthy volunteers during phase I studies. These dose-response studies are usually performed according to a cross-over design. Among the many techniques proposed for assessing the effects of beta-blockers in man, isoprenaline and dynamic exercise tests are the most commonly used. The second step is to make use of the previous results to find the right dose for hypertensive patients in phase II studies. However, many individual factors which can influence the blood pressure response should be kept in mind, especially the initial blood pressure level. The choice of the design is generally based on the need to have repeated administration in order to obtain optimum control of the hypertension. Therefore, the cross-over design, although theoretically the best one, is rarely used on account of its practical and ethical problems. In contrast, the parallel design, with random assignment of treatments, is suitable to most experimental situations. Very different in nature, the stepped dose design stems from an ethical and practical approach of dose finding and thus is also widely used. Finally, correct measurement techniques of blood pressure are required.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879478 TI - Effects of beta-adrenergic blockade on the arterial vasculature in essential hypertension. AB - The effect of beta-blockade was studied in 3 different kinds of human hypertension: borderline, sustained and isolated systolic hypertension. Young patients with borderline hypertension had a similar decrease in cardiac output with both nonselective and selective beta-blockade. Only nonselective beta blockade decreased brachial artery blood flow and increased forearm vascular resistance. In patients with sustained essential hypertension, chronic administration of 2 nonselective beta-blockers, propranolol and pindolol, caused a similar significant decrease in blood pressure with different effects on forearm circulation. Pindolol produced a significant vasodilation of both large and small arteries of the forearm while propranolol did not. In patients with isolated systolic hypertension, short-term beta-adrenergic blockade with propranolol had different effects according to age. In younger patients, propranolol significantly decreased systolic pressure with a concomitant increase in rapid ventricular ejection. In older patients, a lack of systolic pressure reduction was observed with an increase in total peripheral resistance and a decrease in systemic arterial compliance. The results suggested that beta adrenergic blockade in hypertension may affect blood vessels with different effects, according to age, to the characteristics of hypertension and to the specific properties of the beta-blocking agent. The vascular effects involve not only resistive vessels but also large arteries. PMID- 2879477 TI - Antihypertensive effects of tertatolol: 3-month comparative study against acebutolol. AB - Thirty-two hypertensive patients (mean age 52.9 +/- 1.7 years) with a supine diastolic blood pressure (DBP) between 95 and 130 mm Hg (mean 104.3 +/- 0.8) received, following a randomized allocation, either tertatolol 5 mg (n = 16) or acebutolol 400 mg (n = 16) in a single daily dose. The 2 drugs were administered during a 3-month treatment period (from day 0 to day 90) in a single-blind fashion. At rest (n = 32), the decrease of supine systolic blood pressure (SBP) reached 27.3 mm Hg after 1 month of tertatolol treatment (from day 0 to day 30; p less than 0.01); there was a further decrease of 5.1 mm Hg from day 30 (D30) to day 90 (D90) (NS). The corresponding decreases after acebutolol treatment reached respectively 22.3 mm Hg (p less than 0.01) and 5.7 mm Hg (p less than 0.05). Similar results were observed in the upright position. The decrease of supine DBP reached 14.0 mm Hg in patients treated with tertatolol from D0 to D30 (p less than 0.01); a further decrease of 2.9 mm Hg occurred from D30 to D90 (NS). The corresponding decreases in patients administered acebutolol reached respectively 7.6 mm Hg (p less than 0.01) and 5.2 mm Hg (p less than 0.01). Similar results were observed in the upright position. On submaximal exercise (ergometric bicycle; n = 18), the decrease of SBP reached respectively 31.3 mm Hg during tertatolol treatment from D0 to D30 (p less than 0.01) and 8.8 mm Hg from D30 to D90 (NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879479 TI - Reversal of left ventricular hypertrophy following treatment with beta-blockers: experience with tertatolol. AB - Hypertrophy in response to increasing blood pressure in primary hypertension leads to important functional consequences for the left ventricle. In fact, the progression of hypertensive heart disease, from an adaptive left ventricular hypertrophy with compensated ventricular function to severe hypertrophy with left ventricular failure, has been long thought to be related to the severity and duration of hypertension. Antihypertensive treatment seems to prevent or minimize the occurrence of left ventricular hypertrophy, but questions arise as to whether this therapy is also able to restore normal hemodynamic conditions, or at least to minimize the hemodynamic abnormalities. This review aims at summarizing current knowledge on the effects of the antihypertensive treatment with beta blockers, including tertatolol, on hypertension-induced left ventricular hypertrophy. The pathogenetic mechanisms underlying the cardiovascular changes associated with hypertension are discussed. A decrease in left ventricular wall thickness as well as in left ventricular mass has been reported in most of the studies performed with different types of beta-adrenergic blocking agents. The extent of this reduction seems to be related not only to the fall in systemic blood pressure, but also to a decrease in sympathetic stimulation. With regard to the functional consequences of hypertension, the reversal of left ventricular hypertrophy following antihypertensive treatment with beta-blockers is usually associated with an improvement in left ventricular performance. This phenomenon can hardly be ascribed to the direct effects of beta-blocking agents. It is more likely to be related to the concomitant reduction in the afterload and to the improved left ventricular compliance, associated with a decrease in left ventricular wall thickness. PMID- 2879481 TI - Hypofrontality in schizophrenia as assessed by PET. PMID- 2879482 TI - Behavioral and neurochemical changes in pups prenatally exposed to methamphetamine. AB - Behavioral and neurochemical changes were examined in pups after repeated prenatal treatment with methamphetamine (MAP). MAP-pretreated pups showed decreased total motor activity with increased vertical activity. The reactivity to sound stimuli in MAP-pups differed from that in controls, suggesting impaired reactivity to the surroundings. No difference was found in development of the circadian rhythm of motor activity between MAP- and control pups. No behavioral sensitization to MAP was found in MAP-pups, regardless of the repeated prenatal exposure to MAP. This finding suggests that there is a certain developmental stage of the brain that is critical for long-term sensitization to dopamine agonists due to chronic MAP administration. Coincident with this, no change was found in the striatal catecholamine concentrations in MAP-pups. Radioreceptor assaying of various neurotransmitter receptors showed a significant decrease in the Bmax of 3H-spiperone binding in the frontal cortex of MAP-pups. These findings suggest that prenatal treatment with MAP produces impaired reactivity to the surroundings, in which the hyperserotonergic state of the frontal cortex may play an important role. PMID- 2879480 TI - Multiple peroxisomal enzymatic deficiency disorders. A comparative biochemical and morphologic study of Zellweger cerebrohepatorenal syndrome and neonatal adrenoleukodystrophy. AB - Biologic, morphologic, and biochemical investigations performed in 2 patients demonstrate multiple peroxisomal deficiencies in the cerebrohepatorenal syndrome of Zellweger (CHRS) and neonatal adrenoleukodystrophy (NALD). Very long chain fatty acids, abnormal bile acids, including bile acid precursors (di- and trihydroxycoprostanoic acids), and C29-dicarboxylic acid accumulated in plasma in both patients. Generalized hyperaminoaciduria was also present. Peroxisomes could not be detected in CHRS liver and kidney; however, in the NALD patient, small and sparse cytoplasmic bodies resembling altered peroxisomes were found in hepatocytes. Hepatocellular and Kupffer cell lysosomes were engorged with ferritin and contained clefts and trilaminar structures believed to represent very long chain fatty acids. Enzymatic deficiencies reflected the peroxisomal defects. Hepatic glycolate oxidase and palmitoyl-CoA oxidase activities were deficient. No particle-bound catalase was found in cultured fibroblasts, and ether glycerolipid (plasmalogen) biosynthesis was markedly reduced. Administration of phenobarbital and clofibrate, an agent that induces peroxisomal proliferation and enzymatic activities, to the NALD patient did not bring about any changes in plasma metabolites, liver peroxisome population, or oxidizing activities. PMID- 2879483 TI - Analysis of sialidase and N-acetylneuraminate pyruvate-lyase substrate specificity by high-performance liquid chromatography. AB - A rapid and sensitive assay by high-performance liquid chromatography for determination of the activity and substrate specificity of sialidase (EC 3.2.1.18) and N-acetylneuraminate lyase (EC 4.1.3.3) is described. Sialic acids were separated on a strong anion-exchange resin using 0.75 mM sodium sulfate as elution medium. This method allows the determination of a minimum amount of 200 pg (0.6 pmol) of sialic acid. Usually the enzyme mixtures were directly applied to the column without prior purification of substrates and products. The action of sialidase was studied either by the decrease of sialyllactose concentration or by the amount of sialic acid liberated. The relative hydrolysis rates of N acetylneuraminyl-alpha(2-3)-lactose, N-glycolylneuraminyl-alpha(2-3)-lactose, N acetylneuraminyl-alpha(2-6)-lactose, N-acetyl-9-O-acetylneuraminyl-alpha(2-3) lactose, and N-acetyl-4-O-acetylneuraminyl-alpha(2-3)-lactose by Vibrio cholerae sialidase were 100, 88, 25, 12, and 0, respectively. The activity of N acetylneuraminate lyase from Clostridium perfringens was determined by measuring the rate of disappearance of sialic acids or the formation of acylmannosamines, which is possible in the same chromatogram. Relative cleavage rates of N acetylneuraminic acid, N-glycolylneuraminic acid, N-acetyl-9-O-acetylneuraminic acid, N-acetyl-7-O-acetylneuraminic acid, and N-acetyl-4-O-acetylneuraminic acid were found to be 100, 67, 24, 3, and 0, respectively. Comparison of the substrate specificities shows that substituents on the neuraminic acid molecule influence the reactions of both enzymes in a similar way. PMID- 2879484 TI - Direct assay for phosphotransacetylase and acetyl-coenzyme A carboxylase by high performance liquid chromatography. AB - A simple and specific assay to measure the activity of two coenzyme A derivative processing enzymes, i.e., phosphotransacetylase (EC 2.3.1.8) and acetyl-coenzyme A carboxylase (EC 6.4.1.2), is described. The assay is based on the HPLC analysis of the short-chain coenzyme A derivatives formed by the enzymatic reaction, viz., acetyl-CoA and malonyl-CoA. For this purpose, ion-pair reversed-phase HPLC conditions are optimized. Furthermore, the influence of several variables on the enzyme reaction is studied in order to get maximum activity. Due to its short analysis time, good selectivity, and chromatogram information, HPLC proves to be an excellent method for the assay of these enzymes. PMID- 2879485 TI - Adaptation of a gamma-glutamyl transpeptidase assay to microtiter plates. AB - A kinetic assay for measuring gamma-glutamyl transpeptidase (GGT) activity has been adapted to microtiter plates and an automated microtiter plate reader. This method permits the simultaneous analysis of enzyme activity in a large number of samples incubated with the chromogenic GGT substrate gamma-glutamyl-p nitroanilide. A major advantage of this assay over previously reported methods is the substantial reduction in the time needed for measuring sample enzyme activity. In addition, reduction of the total assay volume to 0.28 ml conserves both sample and reagents. This method has been calibrated at 23 degrees C using purified GGT, and used to analyze GGT activity in human sera. The assay is sensitive over a range of 3-200 U/liter. PMID- 2879486 TI - Analysis of aspartate and glutamate in human cerebrospinal fluid by high performance liquid chromatography with automated precolumn derivatization. AB - A method is described for the analysis of the neuroexcitatory amino acids, aspartate and glutamate, in human cerebrospinal fluid (CSF) by reverse-phase, high-performance liquid chromatography. Fluorescent isoindole derivatives of the amino acids were prepared by reacting the amino acids with ortho-phthalaldehyde in an automated, precolumn procedure. Chromatographic conditions were developed that resolve the isoindole derivatives of aspartate and glutamate from those of at least 10 unidentified components of CSF. Amino acids were reliably quantified in 5-microliter samples of CSF, and deproteinization of the specimens was not required. Furthermore, it was found that deproteinization by precipitation with strong acid can lead to artifactually high measurements of glutamate. The concentrations of free aspartate and glutamate in lumbar CSF from 15 neurologically normal children were 0.30 +/- 0.11 and 0.48 +/- 0.26 microM (mean +/- SD), respectively. The value for glutamate is considerably lower than has been reported in any previous study of human CSF. PMID- 2879487 TI - Treatment of allergic rhinitis with a new long-acting H1 receptor antagonist: astemizole. PMID- 2879488 TI - A clinical trial using syrup of ipecac and activated charcoal concurrently. AB - A prospective study was conducted to determine if the emetic effects of syrup of ipecac are preserved when activated charcoal is administered prior to emesis. Ten overdose patients who fulfilled the entrance criteria for the study were administered 60 mL syrup of ipecac by a nasogastric tube followed immediately by 500 mL of tap water. Ten minutes after the ipecac was administered, an aqueous slurry of 50 g activated charcoal diluted to 500 mL was instilled down the nasogastric tube and the tube was removed. Emetic response and time to emesis were recorded. Thirty minutes after emesis subsided, a second dose of 50 g activated charcoal (with sorbitol) was administered orally. Emetic responses were noted in all ten patients. The patients averaged 3.7 emetic episodes. Emesis commenced in an average of 13.8 minutes from the start of ipecac administration and concluded in an average of 45.9 minutes. These results in patients are similar to those observed in a previously reported volunteer group similarly treated. This protocol allows early administration of activated charcoal while preserving the emetic properties of syrup of ipecac in the patients treated. PMID- 2879489 TI - Terfenadine (Seldane) is a potent and selective histamine H1 receptor antagonist in asthmatic airways. AB - Terfenadine (Seldane) is a new, highly potent H1 histamine receptor antagonist that in clinically effective doses is free of side effects. Because the low potency and specificity of many H1 receptor antagonists have made it difficult to define the precise role of histamine as a bronchoconstrictor mediator in asthma we have used terfenadine to define the degree and selectivity of H1 blockade that can be achieved in asthmatic airways. In a double-blind study, 9 asthmatic patients received placebo or terfenadine 60, 120, and 180 mg on separate days followed 3 h later by bronchial provocation with increasing concentrations of either histamine or methacholine. Terfenadine at 60, 120, and 180 mg produced significant bronchodilation with increases in FEV1 above baseline of 9.0, 9.5, and 10%, respectively (p less than 0.05, p less than 0.01, p less than 0.01). All 3 doses of terfenadine displaced the histamine-FEV1 concentration response curves in a parallel fashion to the right in all subjects. When the degree of protection against histamine is expressed as a concentration ratio, terfenadine 60, 120, and 180 mg displaced the response curves by factors of 14.8 +/- 4.6, 22.9 +/- 6.7, and 34.3 +/- 8.4. In contrast to its effect on histamine-induced bronchoconstriction, terfenadine failed to protect the airways against the constrictor effect of inhaled methacholine. Thus, terfenadine is a much more potent and selective H1 receptor antagonist in asthmatic airways than previously available antihistamines and should provide a powerful tool to define the contribution of histamine as a bronchoconstrictor mediator in asthma. PMID- 2879490 TI - Interpretations of voltammetry in vivo using dialyzed perfusion. PMID- 2879491 TI - Development of push-pull systems for perfusion of anatomically distinct regions of the brain of the awake animal. PMID- 2879492 TI - The use of in vivo voltammetry to investigate functional recovery with transplants and neurotransmitter interactions in the rat brain. PMID- 2879493 TI - Microcomputer-controlled voltammetry in the analysis of transmitter release in rat brain. AB - Microcomputer-based linear sweep voltammetry with carbon-paste electrodes has the following features: Subtraction of the background current produces a voltammogram with three well-resolved peaks: an ascorbate signal reflecting excitatory amino acid release; a uric acid signal that may be related to purine metabolism; and an HVA signal that is an index of dopamine release under certain conditions. Voltammograms from up to eight electrodes (for example, four electrodes in two rats or two electrodes in four rats) can be recorded simultaneously together with motor activity for each rat over extended periods. Electrodes remain stable over periods of many weeks as measured by the constancy of the mean peak height in a 24-hr period. Microcomputers in voltammetry provide flexibility of all recording parameters and a wide variety of methods of analysis. The combination of stable electrodes and the ability to monitor over extended periods means that interactions between transmitters in different brain regions and their relation to physiological processes can be studied. PMID- 2879494 TI - Electrochemical measurements in brain extracellular fluid space. PMID- 2879495 TI - Amino acid profiles in cortex of conscious rat: recent studies and future perspectives. PMID- 2879496 TI - Electrochemistry in vivo: application to CNS pharmacology. PMID- 2879497 TI - The relative roles of neuronal activity and direct presynaptic mechanisms in controlling the release of dopamine from the cat caudate nucleus. PMID- 2879499 TI - Developmental genetics of hepatic gluconeogenic enzymes. PMID- 2879498 TI - Hormonal modulation of key hepatic regulatory enzymes in the gluconeogenic/glycolytic pathway. PMID- 2879500 TI - The relationship between structure and function for and the regulation of the enzymes of fatty acid synthesis. PMID- 2879501 TI - Molecular basis for the hormonal regulation of the tyrosine aminotransferase and tryptophan oxygenase genes. PMID- 2879502 TI - [Multiple endocrine neoplasms of IIb type]. PMID- 2879503 TI - [The coronary hypertensive: therapeutic principles]. AB - Since arterial hypertension is one the main risk factors of coronary atherosclerosis, the association hypertension-coronary disease is a frequent one. Moreover, arterial hypertension aggravates the coronary disease and this association is therefore of very poor prognosis. However, this prognosis seems to improve with early and adapted treatment based largely at this time on beta blockers and calcium inhibitors. PMID- 2879504 TI - [Current therapeutic concepts in the treatment of myocardial ischemia. Current and future drugs]. AB - If myocardial ischemia always results from an imbalance between the needs and supplies in oxygen of the myocardium cells, the physiopathology of this process seems today infinitely more complex than the mere diminution or interruption of the output in a coronary artery. The extension of atheromatous lesions, the platelets aggregation, thrombosis, the coronary spasm, the release of products from the arachidonic cascade, the reactivity of the vascular endothelium, the profibrinolytic activity of the tissues are many of the intricate factors inducing myocardial ischemia. Cellular alterations, of which some are triggered by the release of oxygenated free radicals, lead then to an irreversible necrosis. The medications used until now in the treatment of angina are oxygen scavengers and research goes on in this direction with vaso-dilators beta blockers, prolonged action nitro-compounds (nicorandil) or nitro-compounds with an action reinforced by N-acetyl-cysteine, bradycardiac derivates of alinidine and the new calcium antagonists dihydropyridine. However, the new physiopathological concepts of ischemia have opened new directions for the research: products which modify the arachidonic cascade by increase of synthesis or release of PGI2 (nafazatrom, defibrotide), by inhibition of TXA2 synthesis or blocking of TXA2 receptors, and similar products of PGI2 (iloprost); thrombolytic agents more specific of thrombin (PTA) or fibrinolysis activators (defibrotide), and anticoagulants with extended action; chelating agents of oxygenated free radicals (peroxide dismutase, catalase, peroxidase) or xanthine oxidase inhibitors; platelets anti-aggregates like ticlopidine which blocks the platelets receptors to fibrinogen, or inhibitors of the synthesis of pro-aggregating agents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879505 TI - Proteinuria following trauma. AB - Thirteen trauma patients admitted to a major injuries unit were classified according to their injury severity. Urinary excretion of total protein, albumin and gamma glutamyl transpeptidase (GGT) activity were assessed over the following 6 days. All patients showed an initial glomerular and tubular proteinuria during the first 24 h which subsided by the second post-trauma day. The excretion of total protein and albumin was positively correlated with injury severity. Those patients with the severest injuries showed a marked recurrent total proteinuria around days 3 to 4 post-trauma which exhibited features of a tubular lesion. The recurrent proteinuria peak coincided with peak levels of serum c-reactive protein (CRP). PMID- 2879506 TI - The hypokalaemia of acute myocardial infarction. PMID- 2879507 TI - [Discovery, anatomical mapping and biosynthesis of various families of endogenous opioid peptides]. AB - The endogenous opioid peptides all contain the enkephalin sequence Tyr-Gly-Gly Phe (-Met/-Leu at their amino-terminus. Three distinct families of these peptides (beta-endorphins, enkephalins and dynorphins) are present in different neuronal pathways within the central nervous system. Molecular genetics have shown that these three families of opioid peptides are derived from three distinct precursors. Pro-opiomelanocortin gives rise to the endorphins, as well as adrenocorticotropic hormone (ACTH) and the melanotropic hormones (MSH's). Met enkephalin, Leu-enkephalin and the related heptapeptide Met-enkephalin-Arg6-Phe7 and octapeptide Met-enkephalin-Arg6-Gly7-Leu8 are derived from proenkephalin. The third family is derived from prodynorphin and includes dynorphin A, dynorphin B (also known as rimorphin) and alpha- and beta-neo-endorphin. The structures of the genes coding for these precursors are similar, suggesting the possibility of one common ancestral gene. At the present time the main question concerns the physiological significance of such a great diversity of endogenous opioid peptides. PMID- 2879508 TI - Phenotypic modification of human glioma and non-small cell lung carcinoma by glucocorticoids and other agents. AB - Glucocorticoids are cytostatic for human glioma grown at a high cell density in cell culture. The effect is not cytotoxic, appears to involve a modification of the cell surface, and has been detected with methyl prednisolone, dexamethasone, and beta-methasone. Glucocorticoids were also found to reduce malignancy associated properties (plasminogen activator and endothelial mitogenesis) and enhance differentiation (glutamyl synthetase activity and high affinity GABA uptake). Cytostasis was also seen at high cell densities in non-small cell lung carcinoma with a concomitant reduction in plasminogen activator activity and endothelial mitogenesis. Preliminary data on surfactant production in A549 cells suggests that the repression of malignancy-associated properties is accompanied by an increase in cell differentiation. Treatment of the WIL adenocarcinoma gown as a xenograft in nude mice caused total cessation of growth and massive central necrosis in the tumor. PMID- 2879509 TI - Rhodamine 123 and flow cytometry to monitor the cytotoxic actions of nucleoside analogues in nondividing human lymphocytes. AB - We used human lymphocytes from the peripheral blood of normal individuals to compare the cytolytic actions of 2-chloro-2'-deoxyadenosine (2-Cl-dAdo) and 9 beta-D-arabinofuranosylguanine (ara-G). Membrane integrity was ascertained by flow cytometric quantification of the cells' uptake of the fluorescent mitochondria-specific probe rhodamine 123. Addition of 10 microM ara-G to lymphocyte cultures led to a progressive decline in the number of cells that could assimilate rhodamine 123, and after 2 days exposure to drug less than 50% of the cells showed normal staining compared to untreated cells. 2-Cl-dAdo had similar cytotoxic effects at a 0.1 microM concentration. Under the same conditions trypan blue revealed only a 10-20% toxic effect by these drugs. Using rhodamine 123 in combination with the vital stain propidium iodide, we found that 90% of the cells with abnormal rhodamine 123 uptake also stained with propidium iodide. The changes in membrane permeability to fluorescent dyes correlated with the loss of lymphocyte ability to respond to the plant mitogen phytohemagglutinin. Our data indicate that rhodamine 123 is a more sensitive probe than trypan blue for ascertaining early loss of the membrane integrity of dying lymphocytes. Combined with flow cytometry, rhodamine 123 uptake represents a simple and rapid method for identifying the important biochemical events associated with the cytocidal and cytostatic effect of drugs against normal and leukemic cells. PMID- 2879510 TI - Adenosine deaminase complexing protein in cancer studies. AB - ADCP is a dimeric glycoprotein of about 200KD, for which the physiological role is still obscure. This protein occurs mainly in a membrane bound form in various human tissues. In this paper we review the current literature on ADCP in cancer studies. Soluble ADCP was described to be consistently decreased or absent in cancers of lung, liver, kidney and colon. These findings could not be confirmed by immunohistochemical and quantitative biochemical studies in a series of colorectal-, prostatic-, and renal carcinomas. Only in a third of these tumors a decrease could be demonstrated, whereas in the other cases unaltered or even increased amounts were observed. However, in virally transformed human fibroblasts a consistent decrease or complete absence of ADCP was seen, while primary fibroblasts were found to contain high amounts of this protein. Recently, the use of ADCP as a differentiation marker in colonic cancer has been advocated. Furthermore the presence of ADCP in the serum of renal adenocarcinoma patients was found to be indicative of a better chance of five year survival. These studies suggest that ADCP may be a differentiation marker useful for immunohistochemical characterization of colonic and renal carcinomas as well as a serum marker useful for follow-up studies of these types of cancer, analogous to CEA. Finally, ADCP has been found to be selectively expressed by certain T-cell subsets and henceforth may be useful in the studies on leukemias. PMID- 2879511 TI - Escherichia coli H+-ATPase: loss of the carboxyl terminal region of the gamma subunit causes defective assembly of the F1 portion. AB - Mutant genes for the gamma subunit of H+-translocating ATPase (H+-ATPase) were cloned from eight different strains of Escherichia coli isolated in this laboratory. Determination of their nucleotide sequences revealed that they are amber nonsense mutations: a Gln codon at position 15, 158, 227, 262, and 270, respectively, was replaced by a termination codon in these strains. As terminal Met is missing in the gamma subunit, these results indicate that these strains are capable of synthesizing fragments of gamma subunits of 13, 156, 225, 260, and 268 amino acid residues, respectively. Studies on the properties of membranes of these strains suggested the importance of the region between Gln 269 and the carboxyl terminus (residue 286) for forming a stable F1 complex with ATPase activity and the region between Gln 226 and Gln 261 for normal interaction of F1 with F0. The sequence from Gln 261 to Gln 269 also seemed to be important for stability of F1 assembly on the membranes. The high frequency of the nonsense mutations suggested that the number of essential residues is limited in this subunit. Comparison of the homologies of the amino acid sequences of the gamma subunits from four different sources confirmed this notion: 19% of amino acid residues are identically conserved in these four strains, and the conserved regions are the amino terminal and carboxyl terminal regions. PMID- 2879512 TI - The involvement of catalytic site thiol groups in the activation of soluble guanylate cyclase by sodium nitroprusside. AB - Sodium nitroprusside, a potent activator of soluble guanylate cyclase, potentiated mixed disulfide formation between cystine, a potent inhibitor of the cyclase, and enzyme purified from rat lung. Incubation of soluble guanylate cyclase with nitroprusside and [35S]cystine resulted in a twofold increase in protein-bound radioactivity compared to incubations in the absence of nitroprusside. Purified enzyme preincubated with nitroprusside and then gel filtered (activated enzyme) was activated 10- to 20-fold compared to guanylate cyclase preincubated in the absence of nitroprusside and similarly processed (nonactivated enzyme). This activation was completely reversed by subsequent incubation at 37 degrees C (activation-reversed enzyme). Incorporation of [35S]cystine into guanylate cyclase was increased twofold with activated enzyme, while no difference was observed with activation-reversed enzyme, compared to nonactivated enzyme. Cystine decreased the activity of nonactivated and activation-reversed enzyme about 40% while it completely inhibited activated guanylate cyclase. Mg+2- or Mn+2-GTP inhibited the incorporation of [35S]cystine into nonactivated or activated guanylate cyclase. Also, diamide, a potent thiol oxidant that converts juxtaposed sulfhydryls to disulfides, completely blocked incorporation of [35S]cystine into nonactivated or activated guanylate cyclase. These data indicate that activation of soluble guanylate cyclase by nitroprusside results in an increased availability of protein sulfhydryl groups for mixed disulfide formation with cystine. Protection against mixed disulfide formation with diamide or substrate suggests that these groups exist as two or more juxtaposed sulfhydryl groups at the active site or a site on the enzyme that regulates catalytic activity. Differential inhibition by mixed disulfide formation of nonactivated and activated enzyme suggests a mechanism for amplification of the on-off signal for soluble guanylate cyclase within cells. PMID- 2879513 TI - [A case of adult T cell leukemia treated with a new chemotherapeutic agent, KM2210]. AB - A 58-year-old man, born in Nagasaki prefecture, was admitted to our hospital because of anorexia and general fatigue on November 22, 1984. Hepatosplenomegaly was found without skin eruption. The blood examination on admission revealed leukocytosis (50,800/microliter) and atypical lymphocytes with hyperlobulated nuclei. He had hypercalcemia, and hepatic and renal damage. A diagnosis of adult T cell leukemia (ATL) in the acute stage was made. Treatment with KM2210, a conjugate of chlorambucil and estradiol, was started, and his peripheral leukocytes decreased gradually reaching, 19,700/microliter by the end of this medication. His leukocyte count continued to decrease after discontinuation of KM2210 and reached a nadir of 4,700/microliter. Hepatosplenomegaly and hypercalcemia also improved. About one month later, recurrence of the disease occurred and he was again treated with KM2210. Although the second course of the KM2210 therapy was also successful in relieving hepatosplenomegaly and leukocytosis, it proved impossible to ameliorate his poor condition and he died of DIC. Our case suggests that KM2210 has a remarkable cytotoxic effect against ATL cells even in the acute stage but the optimal schedule of treatment with this new drug should be established in order to obtain more satisfactory therapeutic results. PMID- 2879514 TI - Aortic valve replacement for acute Takayasu's disease. AB - A patient with aortic insufficiency secondary to Takayasu's disease who was treated by aortic valve replacement during active aortic inflammation is described. The patient remains well 29 months postoperatively with minor additional treatment. A review of aortic insufficiency in Takayasu's disease is presented. PMID- 2879515 TI - Vein graft failure and selection of conduits for coronary artery bypass operations. PMID- 2879517 TI - [Hemorrhagic fever with renal syndrome in Madagascar. First seroepidemiologic survey of rat populations]. PMID- 2879516 TI - [Arbovirus-vector-vertebrate cycles in Madagascan forests]. PMID- 2879518 TI - Morphine-like analgesics and convulsive threshold for pentetrazole in dogs. AB - In dogs, the influence of morphine (1 mg/kg i.m.), fentanyl (10 and 30 micrograms/kg i.v.), meperidine (6 mg/kg i.m.), and pentazocine (3 mg/kg i.m.) on the pentetrazole seizure threshold was studied. Pentetrazole was infused i.v. at a rate of 10 mg/kg per min up to the first generalized myoclonic jerk. The analgesic treatments lowered the seizure threshold considerably in 5 out of 6 dogs, and fentanyl and pentazocine led to an increased incidence of clonic-tonic seizures after the end of the pentetrazole infusion. PMID- 2879519 TI - The potentiation of morphine-withdrawal jumping by clonidine is antagonized by m chlorophenylpiperazine and not by haloperidol. AB - Administration of naloxone (0.5 mg/kg i.p.) to morphine-dependent rats induced a strong withdrawal syndrome consisting of body shakes, escape jumping and various autonomic signs. Clonidine (750 micrograms/kg s.c.) had a dual action on naloxone precipitated withdrawal symptoms in rats: a suppressive action on body shakes and a potentiating action on jumping. Both actions were found to be mediated by alpha 2-receptors which generally are responsible for sedative effects. Therefore, the action of alpha 2-agonists such as clonidine and azepexole was studied more extensively. Since both serotonergic and dopaminergic systems have been suggested to be involved in morphine-withdrawal jumping, the interaction of clonidine and azepexole with serotonergic and dopaminergic drugs was studied. Neither haloperidol (0.3 mg/kg i.p.) nor the benzamides sulpiride (40 mg/kg p.o.) and metoclopramide (8 mg/kg i.p.) affected the jumping potentiated by the alpha 2 agonists. However, the serotonin-agonist m-chlorophenylpiperazine (2.5 mg/kg i.p.) suppressed the effects of clonidine. Precipitation of jumping in morphine dependent animals was more effective using bremazocine (1.0 mg/kg i.p.). This effect again could be potentiated by clonidine (750 micrograms/kg s.c.). A low dose of m-chlorophenylpiperazine (0.03 mg/kg i.p.) antagonized the clonidine effect without affecting the basal jumping response. The data suggest that clonidine potentiates naloxone-precipitated jumping by decreasing serotonergic output while the administration of m-chlorophenylpiperazine can counteract this lack of serotonergic activity. PMID- 2879520 TI - [Malignant arterial hypertension in periarteritis nodosa. Incidence, clinicobiologic parameters and prognosis based on a series of 165 cases]. AB - The authors studied clinical and biological data occurring in 165 patients observed during 23 years and afflicted with polyarteritis nodosa. Hypertension was present in 52 patients (31.5%) and seven of them suffered from malignant hypertension (4%). Mean age of patients (6 male, 1 female), with malignant hypertension was 38 +/- years old. Mean follow up was 49 +/- 28 months including 26 +/- 21 months after discontinuation of treatment of polyarteritis nodosa. Malignant hypertension occurred during the first year of evolution of polyarteritis nodosa. Renal insufficiency was present in 5 of 7 patients. Proteinuria was greater than 1 gr/d in 4 cases. Renal arteriography was performed in 6 patients and showed in every case renal ischemia and microaneurysms in five. In 4 patients measurements of plasma renin activity and of aldosterone were obtained. A stimulation of those hormones was demonstrated. Some symptoms of polyarteritis nodosa were present with a high incidence in case of malignant hypertension: digestive signs (6/7), orchitis (3/6). HBs antigen was present in 6 cases and hepatitis in 5. Captopril was effective in every case, alone or associated with other treatments. Follow up of hypertension went from 8 months to 4 years. At present time 6 patients are alive and one is lost of follow up. A treatment is necessary in 6 of 7 patients. Creatininemia is greater than 300 micromol/l in 4 patients. A successful kidney transplantation was performed in one case. Our study shows a close relation between malignant hypertension observed in polyarteritis nodosa, vascular nephropathy, digestive and urologic signs. Hepatitis B virus could be responsible of those manifestations. PMID- 2879521 TI - [Effect of the thymus on the development of genetic hypertension in the Lyons strain rat (LH)]. AB - The aim of this work was to determine the part played by the thymus in the development genetic hypertension. This study was conducted in the genetically hypertensive rats (LH) of the lyon strain and their two simultaneously selected controls: the normotensive (LN) and low blood pressure (LL) rats. Systolic blood pressure (SBP) and immunological characteristics were investigated in sham operated and neonatally thymectomized rats of the 3 strains. At 5 weeks of age, sham-operated LH rats exhibited a higher SBP (122 +/- 4 mmHg) than LN (111 +/- 2 mmHg) and LL (100 +/- 2 mmHg) controls. White blood cell numbers and percentage of circulating lymphocytes, thymus histology as well as T cells and T subsets percentages in that organ did not significantly differ within the 3 strains. On the contrary, in the animals of the 3 strains, a positive relationship could be established between the SBP and the proliferative response of the splenocytes to Pokeweed-Mitogen (r = 0.93; N = 30; p less than 0.001) or to Concanavalin A (r = 0.42; n = 30; p less than 0.05). After neonatal thymectomy the SBP of LH rats was more markedly decrease than that of LN and LL rats and established as follows: 103 +/- 2 mmHg; 102 +/- 2 mmHg; 97 +/- 2 mmHg for LH, LN and LL respectively. 21 weeks after thymectomy the SBP remained significantly decrease in LH rats only 160 +/- 5 mmHg vs 177 +/- 6 mmHg in sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879522 TI - [Behavioral features of the fetus, the neonate and the infant caused by maternal neurotropic drug ingestion. Feto-infantile pharmaco and iatrogenic etiopathology]. PMID- 2879523 TI - Prolonged pharmacologic activity of neuroleptic drugs. PMID- 2879524 TI - [Polyarteritis nodosa: report of a case with angiographic study]. AB - A case of polyarteritis nodosa (PAN) in a 54 year-old man is presented. The clinical picture showed a 6-month history of mixed sensorimotor distal symmetrical polyneuropathy in all limbs together with anorexia, weight loss, fatigue, arthralgia, myalgia, mild fever and hypertension. The laboratory studies showed leucocytosis, elevated ESR, positive HBsAg and presence of cryoglobulins. Selective renal, celiac and mesenteric angiography was performed by femoral approach and has showed innumerable aneurysms most of them in hepatic and renal circulation. After about two weeks death has occurred. A brief discussion is done on clinical aspects of PAN pointing out the importance of HBsAg determination on etiopathogenesis and angiographic study on diagnosis. PMID- 2879525 TI - Synthesis and secretion of protein by hepatocytes entrapped within calcium alginate. AB - The ability of entrapped hepatocytes to secrete plasma proteins was examined for the purpose of developing a biological artificial liver. Hepatocytes were isolated from adult rat liver by perfusion with collagenase. Isolated hepatocytes were entrapped within calcium alginate. The entrapped cells induced tyrosine aminotransferase (TAT) in the presence of dexamethasone and dibutyryl-cyclic AMP and retained the ability to induce TAT for 7 days. Moreover, entrapped cells could synthesize and secrete a biologically active form of coagulation Factor II, prothrombin. Two plasma proteins, lecithin: cholesterol acyltransferase and cholinesterase, were also secreted into the medium. Thus, hepatocytes within calcium alginate showed liver-specific characteristics, and these activities were almost comparable with those of monolayer-cultured cells. PMID- 2879526 TI - Sandwich enzyme-immunoassay for dipeptidyl aminopeptidase IV in the serum of people with oral cancer. AB - A highly-sensitive sandwich enzyme immunoassay for serum dipeptidyl aminopeptidase IV (DAP IV) was developed; its level in sera of patients with oral cancer [1.50 +/- 0.35(SD)mg/l serum] was significantly lower than in normal subjects [2.27 +/- 0.77(SD)mg/l serum]. PMID- 2879527 TI - The pathogenicity and cultural characteristics of virulent, intermediate and benign strains of Bacteroides nodosus causing ovine foot-rot. AB - The relationship between the cultural and biochemical characteristics of 22 strains of Bacteroides nodosus and their virulence for sheep was examined. Virulent, intermediate and benign strains were recognised. Although there was some relationship between virulence and colony morphology on hoof medium with 4% agar, colonies of one virulent and 4 intermediate strains resembled those of benign strains. However, on hoof medium with 2% agar and on blood Euonagar, colonies of this virulent and one intermediate strain differed from each other and the other 3 intermediate strains, which in turn differed from the benign. The degree of piliation, as assessed by electron microscopy, was not a reliable indicator of virulence in strains not possessing a beaded colony type. Together, the results of colony morphology and proteolytic tests such as zymogram, degrading proteinase and elastin-agar tests allowed better discrimination of virulent and benign strains. Intermediate strains generally possessed virulent protease activity. In strains with benign zymogram patterns, activity bands 2 and 3 were more labile than in strains with virulent patterns. The addition of CaCl2 to the culture medium resulted in greater stability of proteolytic activity, particularly with benign strains, and prevented the disappearance of protease activity in the band 5 position in virulent, intermediate and benign strains during prolonged incubation. There were slight differences in the sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) patterns of outer membrane proteins of some benign strains but those of intermediate category resembled virulent strains. There was some relationship between the apparent Mr of the pilin monomer on SDS-PAGE gels and serogroup specificity. PMID- 2879528 TI - Characterisation and quantitation of pilus antigens of Moraxella bovis by ELISA. AB - Hyperimmune serums raised in rabbits to purified pili from 9 Australian and 2 American strains of Moraxella bovis from infectious bovine keratoconjunctivitis (IBK) affected herds were used to study the degree of binding between combinations of antigen and antiserum in a conventional enzyme linked immunosorbent assay (ELISA). With the aid of appropriate absorption tests major antigenic differences among pili were found permitting 6 distinct serogroups to be recognised. Further, production of specific antiserums to representative strains of each serogroup in goats facilitated the development of a double antibody sandwich ELISA which could be used to quantitate pilus expression of a given strain of M. bovis, or to differentiate pilus serogroups of 22 strains of M. bovis obtained from a total of 12 Australian herds. Most isolates were found to belong to serogroups designated IV and V. One strain from the United States of America showed total homology with Australian serogroup IV while the other showed some cross-reactivity with serogroups V and VI. PMID- 2879529 TI - The safe use of high dose neuroleptics in a psychiatric intensive care unit. AB - A review of the use of high dose neuroleptics in the management of acute psychoses in a psychiatric intensive care unit confirms the previously reported safety of such regimes. The risk of extreme unwanted effects, such as cardiac arrest and sudden death, was considerably less than the risk of suicide as an inpatient. Although high doses of neuroleptics appear to be relatively safe, there is no advantage, in terms of the length of admission required in the intensive care unit, in using a dose of neuroleptic above the equivalent of 60-80 mg of haloperidol in any one 24-hour period. PMID- 2879530 TI - The role of acetyl-CoA carboxylase phosphorylation in the control of mammary gland fatty acid synthesis during the starvation and re-feeding of lactating rats. AB - Activation of acetyl-CoA carboxylase during incubation of crude extracts of lactating rat mammary gland with Mg2+ and citrate can be blocked by NaF, suggesting that it represents a dephosphorylation of the enzyme. The greater extent of activation in extracts from 24 h-starved rats (200%) compared with fed controls (70%) implies that the decrease in acetyl-CoA carboxylase activity in response to 24 h starvation may involve increased phosphorylation of the enzyme. Acetyl-CoA carboxylase was purified from the mammary glands of lactating rats in the presence of protein phosphatase inhibitors by avidin-Sepharose chromatography. Starvation of the rats for 24 h increased the concentration of citrate giving half-maximal activation by 75%, and decreased the Vmax. of the purified enzyme by 73%. This was associated with an increase in the alkali-labile phosphate content from 3.3 +/- 0.2 to 4.5 +/- 0.4 mol/mol of enzyme subunit. Starvation of lactating rats for 6 h, or short-term insulin deficiency induced by streptozotocin injection, did not effect the kinetic parameters or the phosphate content of acetyl-CoA carboxylase purified from mammary glands. The effects of 24 h starvation on the kinetic parameters and phosphate content of the purified enzyme were completely reversed by re-feeding for only 2.5 h. This effect was blocked if the animals were injected with streptozotocin before re-feeding, suggesting that the increase in plasma insulin that occurs on re-feeding was responsible for the activation of the enzyme. The effects of re-feeding 24 h starved rats on the kinetic parameters and phosphate content of acetyl-CoA carboxylase could be mimicked by treating enzyme purified from 24 h-starved rats with protein phosphatase-2A in vitro. Our results suggest that, in mammary glands of 24 h-starved lactating rats, insulin brings about a dephosphorylation of acetyl-CoA carboxylase in vivo, which may be at least partly responsible for the reactivation of mammary lipogenesis in response to re-feeding. PMID- 2879531 TI - Differential effect of cis-platinum (cis-diamminedichloroplatinum) on regulation of liver and kidney haem and haemoprotein metabolism. Possible involvement of gamma-glutamyl-cycle enzymes. AB - The treatment of rats with cis-platinum (cis-diamminedichloroplatinum) for 1, 3 or 7 days elicited vastly different responses in the liver and the kidney in activities of enzymes of haem-metabolism pathway and gamma-glutamyl-cycle enzymes. The differences resided in the magnitude, direction and the time course of responses. In general, the liver was by far less severely affected, and when a response was elicited, it displayed an earlier onset (1-3 days), with a return to normal at 7 days. In the kidney, however, the effects were notable after 3 days of treatment, and became more pronounced at 7 days. Specifically, the activity of 5-aminolaevulinic acid (ALA) synthetase and contents of cytochrome P-450 and the microsomal haem were decreased in the liver. In contrast, in the kidney, cytochrome P-450 and haem concentrations were significantly increased, with no change in ALA synthetase activity. The increase in the kidney haem content appeared to reflect an increased formation of haem, as suggested by the elevated activity of ferrochelatase and the concomitant decrease in tissue porphyrin levels. In the kidney, a time-dependent and pronounced inhibition of activities of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in glutathione production, and gamma-glutamyl transpeptidase, the first enzyme in glutathione breakdown, were observed. The enzyme activities, 7 days after treatment, were only 40 and 60% of the control values respectively. In contrast, these enzyme activities were not affected in the liver. Complexing cis-platinum with cysteine considerably intensified the entire spectrum of effects of cis-platinum in the kidney. Notably, cytochrome P-450 concentration and haem oxygenase activity were increased to about 3.5 and 6 times the control values, respectively. gamma Glutamylcysteine synthetase activity was decreased to less than 20% of the control. It is suggested that the differential effectiveness of cis-platinum in the liver and the kidney in alternating haem metabolism is related to the vast differences which exist between these organs in the activities of gamma-glutamyl cycle enzymes. It is further suggested that this may promote the formation in the kidney, but not in the liver, of a cis-platinum-cysteine complex that is more stable, and thus biologically more effective, than the parent compound. PMID- 2879532 TI - Differential tissue expression of the glutathione transferase multigene family. AB - The content of GSH transferase mRNAs in poly(A)-containing RNA isolated from eight rat tissues was examined by immunoprecipitation of cell-free translation products and by Northern blotting. Considerable tissue-specific distribution and heterogeneity of immunoprecipitable GSH transferase subunits 1 and 2 synthesized in vitro was observed. These results were confirmed by Northern blotting using a 32P-labelled subunit 1 cDNA probe. The same probe, used in a Southern blot analysis of genomic DNA, provided confirmation that GSH transferase subunits 1 and 2 comprise a multigenic family in the rat. The results show that the selection of cDNA clones coding for chosen subunits can be made easier by making use of qualitative and quantitative tissue differences in GSH transferase mRNAs. PMID- 2879534 TI - The stimulation of glycogenolysis in isolated hepatocytes by opioid peptides. AB - The opioid peptides [Leu]enkephalin and dynorphin-(1-13) were shown to enhance glycogen breakdown when added directly to hepatocytes. This was the result of a concerted effect on the enzymes of glycogen metabolism, with a stimulation of glycogen phosphorylase activity and a simultaneous decrease in glycogen synthase I activity. The latter only became significant when the enzyme was activated by incubating the cells in presence of 20 mM- or 40 mM-glucose. The effect of the opioid peptides was independent of an increase in cyclic AMP or any change in the activity ratio of the cyclic AMP-dependent protein kinase and was abolished by depleting the cells of Ca2+. Both [Leu]enkephalin and dynorphin-(1-13) produced a significant decrease in cyclic AMP formation, suggesting that in liver, as in neuronal tissue, they may act by inhibiting adenylate cyclase activity. PMID- 2879533 TI - Effects of adrenalectomy before weaning and short- or long-term glucocorticoid administration on the genetically obese Zucker rat. AB - Intact obese rats were hyperinsulinaemic, had higher rates of whole-body fatty acid synthesis, higher activities of hepatic acetyl-CoA carboxylase and tyrosine aminotransferase and a higher hepatic glycogen concentration than intact lean animals. Adrenalectomy abolished all these factors of the obese phenotype. Treatment of adrenalectomized rats with corticosterone for 24 h increased the rate of whole-body fatty acid synthesis to the same extent in both phenotypes, but caused a larger increase in glycogen concentration, tyrosine aminotransferase activity and plasma insulin concentration in obese rats. PMID- 2879535 TI - Monoclonal antibodies against rat kidney gamma-glutamyl transpeptidase show species and tissue specificity. AB - Monoclonal antibodies have been raised against rat kidney gamma-glutamyl transpeptidase (GGT). All five antibodies immunoprecipitate enzyme activity from solubilized kidney brush-border membranes, but not from hepatocellular carcinoma membranes. Three of the antibodies react immunohistochemically with brush-border membranes in sections of adult rat kidney, but none of the antibodies cross-react with sections of guinea-pig, mouse or marmoset kidney or with untreated or carcinogen-treated rat liver. The antibodies do not recognize GGT in foetal-rat kidney and react poorly with kidney from 2-year-old rat. They do react with tubules trapped within mesenchymal kidney tumours induced by dimethylnitrosamine, but epithelial tumours, which are GGT-positive (although much less so than normal kidney), are not immunoreactive. PMID- 2879536 TI - Induction of tyrosine aminotransferase in utero by anti-insulin agents. AB - The hepatic enzyme tyrosine aminotransferase, normally expressed in very low amounts until shortly after birth, is prematurely induced in foetal rats made diabetic by the administration of streptozotocin in utero. Similarly, the enzyme is precociously induced in foetuses if the circulating insulin concentration is artificially decreased by the administration of anti-insulin serum. These observations support the proposal that the natural decrease in plasma insulin, known to occur at birth, is a major contributor to the postnatal induction of tyrosine aminotransferase. PMID- 2879538 TI - Identification of a novel Mr = 76-kDa form of beta-adrenergic receptors. AB - The structure of the human beta-adrenergic receptor in purified basal membranes of human placental syncytiotrophoblast was probed using photoaffinity labeling. Basal membranes display a high specific activity of receptors (4-5 pmol/mg protein) and possess both beta 1- and beta 2-adrenergic receptors subtypes. Autoradiography of membranes that were incubated with the beta-adrenergic antagonist [125I]iodoazidobenzylpindolol, photolyzed and then subjected to sodium dodecylsulfate-polyacrylamide gel electrophoresis, identified four radiolabeled peptides, Mr = 65-kDa, 54-kDa, 43-kDa and a novel higher molecular weight 76-kDa form of the receptor. Photoaffinity labeling of each of these four peptides displayed the pharmacological properties expected for true beta-adrenergic receptors. The 76-kDa photoaffinity labeled receptor peptide observed in human placenta basal membranes has not been reported elsewhere. Competition studies with the beta1-selective ligand CGP-20712A demonstrate that the photoaffinity labeled receptor peptides are composed of both beta 1- and beta 2-adrenergic receptor subtypes. PMID- 2879537 TI - Proton-translocating adenosine triphosphatase of chromaffin-granule membranes. The active site is in the largest (70 kDa) subunit. AB - The proton-translocating adenosine triphosphatase (ATPase) of bovine chromaffin granules contains up to five different polypeptides. Its activity is inhibited by N-ethylmaleimide, and ATP protects the enzyme from inhibition. After treatment of membranes with N-[2-3H]ethylmaleimide, only one polypeptide is strongly radiolabelled: this is the largest (70 kDa) subunit of the proton-translocating ATPase. This subunit therefore contains the ATP-hydrolysing site. Two-dimensional electrophoresis reveals heterogeneity in this polypeptide. PMID- 2879540 TI - Enhancer binding proteins predicted by informational spectrum method. AB - Enhancer sequences analysed using the informational spectrum method (ISM) show a characteristic frequency at .0488. It has been shown that the characteristic frequency for some DNA binding proteins overlaps the characteristic frequency of their target DNA sequences. We suggest here that two types of proteins, homeoproteins and the glucocorticoid receptors, might bind to enhancer sequences. PMID- 2879539 TI - Agents inducing high Mg2+-ATPase activity of isolated coupling factor 1 from spinach chloroplasts. AB - Conditions are reported under which purified coupling factor 1 (CF1) from spinach chloroplasts exhibits Mg2+-dependent ATPase activity of about 120 mumoles/min/mg protein. It is shown that CF1, partially activated by treatment with heat and dithiothreitol (DTT), can be further activated by octyl glucoside. The Mg2+ dependent ATPase activity increases linearly as a function of the concentration of octyl glucoside from about 20 mumoles/min/mg protein in the absence of detergent to 120 mumoles/min/mg protein in the presence 15 mM octyl glucoside. This concentration is below the critical micellar concentration (CMC) of the detergent, indicating that the monomeric form is responsible for the activation. Without treatment with heat and DTT, the Mg2+-dependent ATPase activity of CF1 is virtually zero, but can be stimulated by octyl glucoside. In this case, however, only concentrations around CMC give a substantial increase in activity (about 50 mumoles/min/mg at 28 mM octyl glucoside). Concentrations higher than CMC inhibit both latent and heat-activated CF1. PMID- 2879541 TI - Close association between clathrin and the hydrophobic domain of boundary membranes in brain endocytic vesicles. AB - Purified bovine brain clathrin binds readily, in a pH-dependent fashion, to protein-free phospholipid bilayers. The association is tight and leads to inter bilayer fusion, however, photolabeling studies using the amphiphilic photoreactive glycolipid 12-(4-azido-2-nitrophenoxy)stearoyl[1-14C]glucosamine provide no evidence for direct insertion of clathrin into the central, hydrophobic domain of of these target membranes. In contrast, similar photolabeling studies of isolated, intact clathrin-coated vesicles show that, in these structures, clathrin is readily accessible to a probe which is known to reside preferentially within the hydrophobic domain of the membrane. The results are consistent with a natural requirement, by clathrin, for accessory proteins in order to effect membrane penetration. PMID- 2879542 TI - The identification of two subcellular sites for cleavage of gamma glutamyltranspeptidase propeptide. AB - In order to determine the subcellular site(s) of rat renal gamma glutamyltranspeptidase propeptide cleavage labeled immunoprecipitates were obtained from preparations of either intracellular membranes or brush border membrane vesicles. Heterodimer accounts for 25% of the label associated with transpeptidase in intracellular membranes from 5 to 40 min postinjection of [35S]methionine, consistent with a cotranslational cleavage of propeptide in the endoplasmic reticulum. Labeled propeptide and heterodimer appear in the brush border membrane fraction between 20-30 min postinjection and accumulate for 1 h and 4h, respectively. Subsequently, the propeptide disappears with a half-life of 1 h while the heterodimer is relatively stable. These results confirm our previous proposal for two distinct subcellular sites for transpeptidase propeptide cleavage (Capraro, M.A. and Hughey, R.P. (1983) FEBS Lett. 157, 139 143). PMID- 2879543 TI - Translation of messenger RNA of pig kidney D-amino acid oxidase in a cell-free system. AB - In vitro synthesis of D-amino acid oxidase [D-amino acid: O2 oxidoreductase (deaminating), EC 1.4.3.3], one of the peroxisomal flavin enzymes, was performed using a rabbit reticulocyte lysate system in order to elucidate the biosynthetic pathway of the enzyme. The apparent molecular weight of the synthesized enzyme protein was the same as that of D-amino acid oxidase purified from pig kidney. On the other hand, the enzyme protein was not detectable when a wheat germ lysate system was used for the translation. Denaturation of pig kidney poly(A)+ RNA with methylmercury hydroxide prior to the translation was found to enhance the synthesis of the enzyme protein. These results suggest a tight conformational structure of the mRNA used. PMID- 2879544 TI - Sulfasalazine in rheumatoid arthritis. A double-blind, placebo-controlled trial. AB - Sulfasalazine (SSZ), 3 gm daily, was compared with placebo for treatment of rheumatoid arthritis, in a 15-week randomized, parallel, double-blind trial. Joint tenderness and swelling, morning stiffness, grip strength, and pain score all showed significantly more improvement with SSZ than with placebo. Adverse effects, particularly gastrointestinal reactions, led to withdrawal from the study of 28% of the patients who had been receiving SSZ, but these effects were all readily reversible and not life-threatening. These results confirm previous findings that suppression of rheumatoid synovitis may be induced by SSZ, within 2 months after full maintenance doses are reached. PMID- 2879545 TI - Role of alcohol, glucose intolerance and obesity in hypertriglyceridemia. AB - From a primary health screening 631 subjects with serum triglycerides greater than or equal to 4.0 mmol/l were investigated for underlying factors for hypertriglyceridemia. Obesity, glucose intolerance, or suspected high alcohol consumption were associated in 84.5% if the definitions were: Actual/ideal weight (A/I) greater than or equal to 1.2 (obesity), blood glucose in the fasting state or after 120 min of an oral glucose tolerance test (OGTT) greater than or equal to 7.0 mmol/l (glucose intolerance), and gammaglutamyltransferase (GGT) greater than or equal to 1.0 mu kat/l (suspected high alcohol consumption). Ninety-seven percent were associated if also those with positive alcohol anamnesis or with A/I 1.06-1.19, blood glucose after 120 min of an OGTT 6.5-6.99, or GGT 0.8-0.99 were included. PMID- 2879546 TI - [Postoperative drug control of pain]. PMID- 2879547 TI - [Gastrointestinal endocrine cells during the treatment of duodenal ulcer patients with the new peptide preparation dalargin]. PMID- 2879548 TI - A comparison of female and male drivers arrested on suspicion of driving under the influence of alcohol or drugs. PMID- 2879549 TI - [Effect of a new H2 receptor antagonist, famotidine, on gastric secretion]. PMID- 2879550 TI - Lymphocyte gamma-glutamyltranspeptidase activity in ataxia-telangiectasia. AB - gamma-Glutamyltranspeptidase (GGTP) is a membrane-bound enzyme, that catalyzes gamma-glutamyl transfer from gamma-glutamyl compounds to amino acid and peptide acceptors. One of the most important clinical findings about ataxia telangiectasia (A-T), a multisystemic and autosomal-recessive disease, is dysfunction of the immune system. In this study, the activity of GGTP was determined in the lymphocytes from patients with A-T. Lymphocyte GGTP activity in A-T patients was found to be significantly lower than that of control lymphocytes (P less than 0.001). This change may be due to the abnormality in the membrane of lymphocytes of A-T patients. PMID- 2879551 TI - Harvey-ras oncogene restriction fragment alleles in familial melanoma kindreds. AB - Unique and uncommon BamHI allelic restriction fragments of the Ha-ras locus have been reported in the genomes of patients with cancer and of three affected members of a familial melanoma kindred (Krontiris et al., 1986). Analysis of the BamHI and Msp/HpaII restriction fragments of peripheral blood leucocyte DNA from the members of two families with hereditary melanoma (HM)/familial dysplastic naevus syndrome (DNS) revealed that the only Ha-ras allele common to four affected members of one kindred and two from a second kindred, was the 6.7kb allele which is found in 66% of the normal population. This allele was found equally in affected and non-affected family members, and in one affected case was inherited from an unaffected homozygous parent. It was absent in two affected sisters in a third kindred. In the first kindred the karyotype of all three melanoma sufferers was 46XX 9qh+, while six unaffected members had a normal karyotype. BamHI polymorphism of the Ha-ras gene does not identify the affected members in the HM/DNS families studied. PMID- 2879552 TI - NMR analysis and sequence of toxin II from the sea anemone Radianthus paumotensis. AB - Toxin II from Radianthus paumotensis (RpII) has been investigated by high resolution NMR and chemical sequencing methods. Resonance assignments have been obtained for this protein by the sequential approach. NMR assignments could not be made consistent with the previously reported primary sequence for this protein, and chemical methods have been used to determine a sequence with which the NMR data are consistent. Analysis of the 2D NOE spectra shows that the protein secondary structure is comprised of two sequences of beta-sheet, probably joined into a distorted continuous sheet, connected by turns and extended loops, without any regular alpha-helical segments. The residues previously implicated in activity in this class of proteins, D8 and R13, occur in a loop region. PMID- 2879553 TI - Purification and characterization of a molecular weight 100,000 coat protein from coated vesicles obtained from bovine brain. AB - A protein designated as a 100-kDa protein on the basis of sodium dodecyl sulfate gel electrophoresis was purified from coated vesicles obtained from bovine brain, with uncoated vesicles as starting material. Two gel filtration steps, one involving 0.5 M tris(hydroxymethyl)aminomethane, pH 8.0, buffer, and the other 0.01 M tris(hydroxymethyl)aminomethane, pH 8.0, and 3 M urea buffer, were employed. The purified protein has a native molecular weight of 114,000 as determined by sedimentation equilibrium analysis. Circular dichroism data showed that the protein has 28% helical structure, 29% beta-structure, and 15% beta turns, and the rest is random coil. Addition of the purified protein to clathrin results in the polymerization of clathrin to homogeneous size baskets of sedimentation velocity 150 S. A scan of the Coomassie Blue stained electrophoresis gels of the polymerized baskets shows that, for every clathrin trimer, there is approximately one 100-kDa protein molecule. PMID- 2879554 TI - Assessment of a ternary model for the binding of agonists to neurohumoral receptors. AB - A frequently cited variant of the "mobile receptor" hypothesis has been examined for its ability to describe the binding of agonists at neurohumoral receptors that operate via a guanylyl nucleotide binding protein. The model involves a reversible association between the receptor (R) and the G protein (G). Agonists (A) bind with different affinity to R and to the RG complex; similarly, G differentiates between R and the AR complex. Theoretical binding curves calculated according to the model have been analyzed in terms of the Hill equation and as a mixture of independent and noninteracting sites. The model is shown to be compatible in some respects with reported data on the binding of agonists to the beta-adrenergic receptor but not to the muscarinic cholinergic or D2 dopaminergic receptors. It is difficult to reconcile with the reported effects of guanylyl nucleotides, magnesium, and N-ethylmaleimide on the binding of agonists at any neurohumoral receptor. PMID- 2879555 TI - Conformation change of tRNAGlu in the complex with glutamyl-tRNA synthetase is required for the specific binding of L-glutamate. AB - The binding of Thermus thermophilus glutamyl-tRNA synthetase (GluRS) with T. thermophilus tRNAGlu, Escherichia coli tRNAGlu, and amino acids was studied by fluorescence measurements. In the absence of tRNAGlu, GluRS binds with D glutamate as well as L-glutamate. However, in the presence of E. coli tRNAGlu, GluRS binds specifically with L-glutamate. The KCl effects on the Michaelis constants (Km) for tRNAGlu, L-glutamate, and ATP were studied for the aminoacylation of the homologous tRNAGlu and heterologous tRNAGlu species. As the KCl concentration is raised from 0 to 100 mM, the Km value for L-glutamate in the heterologous system is remarkably increased whereas the Km value for L-glutamate in the homologous system is only slightly increased. The circular dichroism analyses were made mainly of the bands due to the 2-thiouridine derivatives of tRNAGlu in the complex. The conformation change of T. thermophilus tRNAGlu upon complex formation with GluRS is not affected by addition of KCl. In contrast, the heterologous tRNAGlu X GluRS complex is in an equilibrium of two forms that depends on KCl concentration. The predominant form at low KCl concentration is closely related to the small Km value for L-glutamate. In this form of the complex, the conformation of tRNAGlu is appreciably different from that of free molecule. Accordingly, such a conformation change of tRNAGlu in the complex with GluRS is required for the specific binding of L-glutamate as the substrate. PMID- 2879556 TI - Reaction energetics of a mutant triosephosphate isomerase in which the active site glutamate has been changed to aspartate. AB - The essential catalytic base at the active site of the glycolytic enzyme triosephosphate isomerase is the carboxylate group of Glu-165, which directly abstracts either the 1-pro-R proton of dihydroxyacetone phosphate or the 2-proton of (R)-glyceraldehyde 3-phosphate to yield the cis-enediol intermediate. Using the methods of site-directed mutagenesis, we have replaced Glu-165 by Asp. The three enzymes chicken isomerase from chicken muscle, wild-type chicken isomerase expressed in Escherichia coli, and mutant (Glu-165 to Asp) chicken isomerase expressed in E. coli have each been purified to homogeneity. The specific catalytic activities of the two wild-type isomerases are identical, while the specific activity of the mutant enzyme is reduced by a factor of about 1000. The observed kinetic differences do not derive from a change in mechanism in which the aspartate of the mutant enzyme acts as a general base through an intervening water molecule, because the D2O solvent isotope effects and the stoichiometries of inactivation with bromohydroxyacetone phosphate are identical for the wild type and mutant enzymes. Using the range of isotopic experiments that were used to delineate the free-energy profile of the wild-type chicken enzyme, we here derive the complete energetics of the reaction catalyzed by the mutant protein. Comparison of the reaction energetics for the wild-type and mutant isomerases shows that only the free energies of the transition states for the two enolization steps have been seriously affected. Each of the proton abstraction steps is about 1000-fold slower in the mutant enzyme. Evidently, the excision of a methylene group from the side chain of the essential glutamate has little effect on the free energies of the intermediate states but dramatically reduces the stabilities of the transition states for the chemical steps in the catalyzed reaction. PMID- 2879557 TI - Glutamic acid-149 is important for enzymatic activity of yeast inorganic pyrophosphatase. AB - Modification of Saccharomyces cerevisiae inorganic pyrophosphatase (PPase) with 1 ethyl-3-[3-(dimethylamino)propyl]carbodiimide is known to lead to a loss of enzymatic activity, the rate of which is decreased in the presence of ligands binding to the active site [Cooperman, B. S., & Chiu, N. Y. (1973) Biochemistry 12, 1676-1682; Heitman, P., & Uhlig, H. J. (1974) Acta Biol. Med. Ger. 32, 565 594]. In this work we show that, when such inactivation is carried out in the presence of [14C]glycine ethyl ester (GEE), GEE is covalently incorporated into PPase, incorporation into the most highly labeled tryptic peptide is site specific, as evidenced by the reduction of such incorporation in the presence of the active site ligands Zn2+ and Pi, the extent of formation of this specifically labeled peptide correlates with the fractional loss of PPase activity, and the specifically labeled peptide corresponds to residues 145-153 and the position of incorporation within this peptide is Glu-149. The significance of our findings for the location of the active site and for the catalytic mechanism of PPase is briefly considered in the light of the 3-A X-ray crystallographic structure of Arutyunyun and his colleagues [Arutyunyun, E. G., et al. (1981) Dokl. Akad. Nauk SSSR 258, 1481-1485; Kuranova, I. P., et al. (1983) Bioorg. Khim. 9, 1611-1919; Terzyan, S. S., et al. (1984) Bioorg. Khim. 10, 1469-1482]. PMID- 2879558 TI - Regulation of acetyl-CoA carboxylase by ADP-ribosylation. AB - Because of certain similarities between acetyl-CoA carboxylase (ACC) and tubulin, and the recent demonstration of the ADP-ribosylation of tubulin by cholera toxin, we have investigated a potential role for ADP-ribosylation in the regulation of ACC activity. Incubation of purified rat liver ACC with cholera toxin in the presence of millimolar concentrations of [adenylate-32P]NAD results in a time dependent incorporation of ADP-ribose into ACC of greater than 2 mol/mol of enzyme subunit, accompanied by a marked inactivation of enzyme activity. This effect is not mimicked by pertussis toxin, ADP-ribose, or ribose 5-phosphate. Incubation of labeled ACC with snake venom phosphodiesterase and alkaline hydrolysis release 32P-products tentatively identified by high-performance liquid chromatography as 5'-[32P]AMP and [32P]ADP-ribose, respectively. These data are consistent with a mono-ADP-ribosylation of ACC catalyzed by cholera toxin. Phosphodiesterase treatment of inactivated ACC partially restores enzyme activity. The effects of ADP-ribosylation of ACC are expressed both as a decrease in the enzyme Vmax and as an increase in the apparent Ka for citrate. These results suggest that ACC might be a substrate for endogenous ADP ribosyltransferases and that this covalent modification could be an important regulatory mechanism for the modulation of fatty acid synthesis in vivo. PMID- 2879559 TI - Agonist interactions at hepatic alpha 1- and beta-adrenergic receptors: affinity state regulation by guanine nucleotides and temperature. AB - We investigated the binding characteristics of agonists to alpha 1- and beta adrenergic receptors of intact liver cells, broken rat liver cell membranes, and detergent-solubilized preparations under varying experimental conditions, focusing on the different "states" of the receptor for agonists and the regulation of these states by temperature and guanine nucleotides. While only low affinity binding of agonists to both receptor subtypes was evident in studies performed at 37 degrees C with solubilized preparations, biphasic competition curves for agonists were observed in both intact cells and membrane preparations; the majority of sites were of low affinity. In membrane preparations, the nonhydrolyzable GTP analogue Gpp(NH)p caused a rightward shift of agonist competition curves and a loss of high-affinity binding. These results are consistent with the involvement of guanine nucleotide binding proteins in both alpha 1- and beta-adrenergic transduction pathways. When competition studies were performed at 4 degrees C, receptor sites existed predominantly in the high affinity configuration, in intact cells and membranes, as well as in soluble preparations. In contrast to the studies conducted at 37 degrees C, no Gpp(NH)p induced conversion to the lower affinity state could be demonstrated in studies performed with membrane preparations at 4 degrees C. Thus, the high-affinity state of alpha 1- and beta-adrenergic receptors is stabilized at 4 degrees C in intact cells, membranes, and soluble preparations. After incubations had been performed at 37 degrees C, high-affinity binding of agonists could not be restored by subsequent incubation at 4 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879560 TI - Activation of Bordetella pertussis adenylate cyclase by the carboxyl-terminal tryptic fragment of calmodulin. AB - Highly purified tryptic fragments of calmodulin were tested for their ability to stimulate adenylate cyclase activity of Bordetella pertussis spheroplast membranes and were compared to their activities on brain Ca2+/calmodulin dependent cyclic nucleotide phosphodiesterase. The C-terminal fragment, consisting of residues 78-148, was a full agonist for the cyclase with 0.1-0.15 the potency of calmodulin but did not stimulate phosphodiesterase. Fragments 1 77, 1-90, and 107-148 stimulated adenylate cyclase (and not phosphodiesterase) at low potency; this was not due to calmodulin contamination, but contamination by fragment 78-148 could not be excluded with certainty. An adduct of norchlorpromazine isothiocyanate and calmodulin showed full agonist activity for adenylate cyclase at 0.01-0.02 the potency of calmodulin. Stimulation of adenylate cyclase by a number of the fragments occurred in the absence of Ca2+, but stimulator potency was enhanced 20-60-fold in its presence. The similarity of Ca2+ requirements of fragment 78-148 and calmodulin suggests that occupancy of the two C-terminal Ca2+ binding sites of calmodulin accounts for most of the Ca2+ enhancement of calmodulin stimulation of adenylate cyclase. PMID- 2879561 TI - Location of lysine-beta 162 in mitochondrial F1-adenosinetriphosphatase. AB - The quenching of the fluorescence of bovine heart F1-adenosinetriphosphatase labeled specifically at its essential Lys-beta 162 with 7-chloro-4-nitro-2,1,3 benzoxadiazole (N-NBD-F1) by 2',3'-O-(2,4,6 trinitrocyclohexadienylidene)adenosine 5'-triphosphate (TNP-ATP) has been studied. Analysis of the fluorescence data in the presence of 1 mM ATP shows that the dissociation constant of TNP-ATP from its first binding site in the covalently labeled enzyme is 250-fold lower than that of ATP, which it replaces in pH 7.0 buffer containing 25% glycerol, and that this binding causes a 54% quenching of the fluorescence of the N-NBD label due to energy transfer to the weakly fluorescent TNP-ATP molecule. Computation based on the observed quenching gives a distance of 25.6 +/- 0.4 A between the NBD label and the chromophore of the bound TNP-ATP molecule. Since the distance between the chromophore and the farthest O atom of the bound TNP-ATP is about 16 A, it seems quite likely that the epsilon-amino group of Lys-beta 162 is near the gamma-phosphate group of the TNP-ATP bound at the catalytic site. Similar measurements in the presence of 1 mM ADP show that the replacement of ADP at the catalytic site by TNP-ATP causes a 49% quenching of the fluorescence of the N-NBD label, which gives a distance of 26.5 +/- 0.4 A between the label and the chromophore of the bound TNP-ATP molecule. PMID- 2879562 TI - Geometric isomers of covalently labeled mitochondrial F1-adenosinetriphosphatase with different properties. AB - Two geometric isomers of covalently labeled F1-adenosinetriphosphatase (F1 ATPase) have been prepared by reaction with 7-chloro-4-nitro-2,1,3-benzoxadiazole (NBD-Cl): a directly labeled product denoted by O-beta'-NBD-F1 and an indirectly prepared product denoted by 0-beta'-NBD-F1. The normal isomer O-beta'-NBD-F1 is highly inhibited, and its label can be removed by 20 microM N-acetyl-L-cysteine (AC) at the expected rate with dr/dn approximately equal to -1, where n is the molar ratio of the label to F1 and r is the ratio of the ATPase activity of the labeled enzyme to that of the unlabeled control enzyme. But O-beta"-NBD-F1 is almost fully active, and its label can be removed by 20 microM AC at much slower rates with dr/dn approximately equal to 0. Cleavage of either isomer with pepsin and subsequent amino acid analysis of the isolated radioactive polypeptides show that the label is attached to Tyr-beta 311 in both isomers. At pH 9 the label in O-beta'-NBD-F1 spontaneously transfers from Tyr-beta 311 to the presumably nearby Lys-beta 162 in the dark with a half-time of 1/2 h, but the label in O-beta"-NBD F1 does not transfer under the same conditions. The existence of geometric isomers of O-NBD-F1 with contrastingly different properties invalidates models for F1 with three equivalent beta subunits but is consistent with the model based on one principal catalytic beta' subunit and two auxiliary beta" subunits. A possible mechanism for promoting the catalytic efficiency of beta' through protein conformation change induced by ATP and/or ADP is suggested. PMID- 2879564 TI - 6-Thiocyanatoflavins and 6-mercaptoflavins as active-site probes of flavoproteins. AB - 6-Thiocyanatoflavins have been found to be susceptible to nucleophilic displacement reactions with sulfite and thiols, yielding respectively the 6-S-SO3 -flavin and 6-mercaptoflavin, with rate constants at pH 7.0, 20 degrees C, of 55 M-1 min-1 for sulfite and 1000 M-1 min-1 for dithiothreitol. The 6-SCN-flavin binds tightly to riboflavin-binding protein as the riboflavin derivative, to apoflavodoxin, apo-lactate oxidase, and apo-Old Yellow Enzyme as the FMN derivative, and to apo-D-amino acid oxidase as the FAD derivative. The riboflavin binding protein derivative is inaccessible to dithiothreitol attack, and the lactate oxidase and D-amino acid oxidase derivatives show only limited accessibility. However, the flavodoxin and Old Yellow Enzyme derivatives react readily with dithiothreitol, indicating that the flavin 6-position is exposed to solvent in these proteins. The lactate oxidase and D-amino acid oxidase derivatives convert slowly but spontaneously to the 6-mercaptoflavin enzyme forms in the absence of any added thiol, indicating the presence of a thiol residue in the flavin binding site of these proteins. The reaction rates have been investigated of 6-mercaptoflavins with iodoacetamide, N-ethylmaleimide, methyl methanethiosulfonate, H2O2, and m-chloroperbenzoate, in both the free and protein bound state. The results confirm the conclusions drawn from the studies with 6 SCN-flavins described above and from 6-N3-flavins [Massey, V., Ghisla, S., & Yagi, K. (1986) Biochemistry (preceding paper in this issue)]. The spectral properties of the protein-bound 6-mercaptoflavin vary widely among the five proteins studied and show stabilization of the neutral flavin with flavodoxin and riboflavin-binding protein and of the anionic species by Old Yellow Enzyme, lactate oxidase, and D-amino acid oxidase. In the case of the latter two enzymes, the stabilization appears to be due to interaction of the negatively charged flavin with a positively charged protein residue located near the flavin pyrimidine ring. This positively charged residue appears to be responsible also for the strong stabilization of the two-electron oxidation state of the mercaptoflavin as the 6-S-oxide. With the other flavoproteins studied this oxidation level is stabilized as the 6-sulfenic acid or 6-sulfenate. PMID- 2879563 TI - 6-Azido- and 6-aminoflavins as active-site probes of flavin enzymes. AB - 6-Azidoflavins have been bound to the apoproteins of five representative flavoproteins and their properties, before and after light irradiation, compared with those of the same proteins containing the appropriate 6-aminoflavin. In the dark the 6-azidoflavoproteins are quite stable, except for L-lactate oxidase, where spontaneous conversion to the 6-amino-FMN enzyme occurs slowly at pH 7. 6 Azido-FMN Old Yellow Enzyme is converted to the 6-amino-FMN enzyme by aerobic turnover with NADPH, and 6-azido-FAD D-amino acid oxidase is converted to the 6 amino-FAD enzyme by treatment with D-alanine. Light irradiation of 6 azidoriboflavin bound to riboflavin-binding protein does not result in any covalent fixation of the flavin to the protein. Light irradiation of 6-azido-FMN flavodoxin gives only a small amount of covalent linkage. In contrast, 6-azido FMN Old Yellow Enzyme undergoes a very facile light-induced change, in which approximately 50% of the flavin is attached in a stable covalent linkage to the protein. The resulting flavoprotein form has lost the ability to bind phenols, a distinctive characteristic of the native enzyme; it does, however, bind NADPH, but the latter cannot reduce the covalently bound flavin. 6-Azido-FAD D-amino acid oxidase also undergoes a facile light modification, in which almost quantitative fixation of the flavin to the protein takes place. The resulting flavoprotein cannot bind benzoate, an active-site ligand for the native enzyme, nor is it reduced anaerobically by D-alanine. The covalent linkage is fairly labile and is destroyed on denaturation of the protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879565 TI - Escherichia coli F1 ATPase is reversibly inhibited by intra- and intersubunit crosslinking: an approach to assess rotational catalysis. AB - Reaction of the multisubunit F1 ATPase from Escherichia coli (EF1) with a bifunctional cleavable crosslinker, 3,3'-dithiobis(succinimidylpropionate) (DSP), has been used to explore the possibility that during catalysis a rotational movement of catalytic subunits relative to noncatalytic subunits occurs. The premise is that such rotational catalysis is tenable if intersubunit crosslinking of a major subunit with one of the minor subunits inhibits the enzyme activity and if upon cleavage of the crosslinks, the enzyme regains activity. The results presented in this paper show that crosslinking of about 5-6 reactive groups on EF1 with DSP is accompanied by a loss of 2/3 of the enzyme activity. Both intra- and intersubunit crosslinks are formed. The most prominent intersubunit crosslinks are those of gamma and delta subunits with the alpha subunit. Nearly complete recovery of activity can be attained by cleaving the disulfide bond in the crosslinker with dithiothreitol. Because the chemical modification of enzyme groups remains after the crosslinker is cleaved, the loss in activity before cleavage can be ascribed to conformational restraints. The results show that catalysis by the EF1 ATPase is highly sensitive to the restrictions of crosslinking, and are consistent with the view that catalysis is accompanied by appreciable movements of the major subunits with respect to the minor subunits, as suggested for rotational catalysis. PMID- 2879566 TI - Amino acid substitutions in the epsilon-subunit of the F1F0-ATPase of Escherichia coli. AB - A mutant strain of Escherichia coli was isolated in which Gly-48 of the mature epsilon-subunit of the energy-transducing adenosine triphosphatase was replaced by Asp. This amino acid substitution caused inhibition of ATPase activity (about 70%), loss of ATP-dependent proton translocation and lowered oxidative phosphorylation, but did not affect proton translocation through the F0. Purified F1-ATPase from the mutant strain bound to stripped membranes with the same affinity as the normal F1-ATPase. Partial revertant strains were isolated in which Pro-47 of the epsilon-subunit was replaced by Ser or Thr. Pro-47 and Gly-48 are predicted to be residues 2 and 3 in a Type II beta-turn and the Gly-48 to Asp substitution is predicted to cause a change from a Type II to a Type I or III beta-turn. Space-filling models of the beta-turn (residues 46-49) in the normal, mutant and partial revertant epsilon-subunits indicate that the peptide oxygen between Pro-47 and Gly-48 is in a different position to the peptide oxygen between Pro-47 and Asp-48 and that the substitution of Pro-47 by either Ser or Thr restores an oxygen close to the original position. It is suggested that the peptide oxygen between Pro-47 and Gly-48 of the epsilon-subunit is involved either structurally in inter-subunit H-bonding or directly in proton movements through the F1-ATPase. PMID- 2879567 TI - On the mechanism of linolenic acid inhibition in Photosystem II. AB - Recent studies in our laboratory have reexamined the interaction of the unsaturated fatty acid, linolenic acid, with Photosystem II and have documented two principal regions of inhibition: one associated with the donor complex (Signal 2f or D1) to the reaction center, and the other located on the reducing side between pheophytin and Qa (Golbeck, J.H. and Warden, J.T. (1984) Biochim. Biophys. Acta 767, 263-271). A further characterization of fatty acid inhibition of secondary electron transport in Photosystem II at room and cryogenic temperatures is presented in this paper. These studies demonstrate that linolenic acid, and related fatty acid analogs, eliminate the transient absorption increase at 320 nm, attributed to Qa-; abolish the production, either chemically or photochemically, of the ESR signal (Q-Fe) associated with the bound quinone acceptor, Qa-; and prevent the photooxidation of Signal 2(1t)(D1) at cryogenic temperature. Linolenic-acid-treated samples are characterized by a high initial fluorescence yield (Fi) equivalent to the maximum level of fluorescence (Fmax); however, the spin-polarized triplet, associated with the reaction-center electron donor, P-680, is observed only in inhibited samples that have been prereduced with sodium dithionite. These results suggest the presence of an additional acceptor intermediate between pheophytin and Qa. The donor-assisted photoaccumulation of pheophytin anion in Photosystem II particles, as monitored by the decline of fluorescence yield, is inhibited by linolenic acid. Redox titrations of the fluorescence yield in control and inhibited preparations demonstrate that the midpoint potential for the primary acceptor for Photosystem II is insensitive to the fatty acid (Em approximately -583 mV) and thus indicate that primary photochemistry is functional during linolenic-acid inhibition. These data are consistent with the hypothesis that unsaturated fatty acids inhibit secondary electron transport in Photosystem II via displacement of endogenous quinone from quinone-binding peptides. PMID- 2879568 TI - The antioxidant activity of haptoglobin towards haemoglobin-stimulated lipid peroxidation. AB - Haemoglobin stimulates the peroxidation of lipids in two discernable phases. The first phase is inhibited by binding haemoglobin to the protein haptoglobin. The second phase is stimulated by complexable iron released from the haemoglobin molecule during the process of lipid peroxidation. This latter peroxidation is inhibitable by transferrin and the iron chelator desferrioxamine. Heat-denatured haemoglobin and haemin both stimulated lipid peroxidation but this is not inhibitable by haptoglobin. It is suggested that the haptoglobins play an important antioxidant role in vivo by preventing iron-stimulated formation of oxygen radicals. PMID- 2879569 TI - Metabolism of opioid peptides by cerebral microvascular aminopeptidase M. AB - Aminopeptidase M (EC 3.4.11.2), which can degrade low molecular weight opioid peptides, has been reported in both peripheral vasculature and in the CNS. Thus, we have studied the metabolism of opioid peptides by membrane-bound aminopeptidase M derived from cerebral microvessels of hog and rabbit. Both hog and rabbit microvessels were found to contain membrane-bound aminopeptidase M. At neutral pH, microvessels preferentially degraded low molecular weight opioid peptides by hydrolysis of the N-terminal Tyr1-Gly2 bond. Degradation was inhibited by amastatin (I50 = 0.2 microM) and bestatin (10 microM), but not by a number of other peptidase inhibitors including captopril and phosphoramidon. Rates of degradation were highest for the shorter peptides (Met5- and Leu5 enkephalin) whereas beta-endorphin was nearly completely resistant to N-terminal hydrolysis. Km values for the microvascular aminopeptidase also decreased significantly with increasing peptide length (Km = 91.3 +/- 4.9 and 28.9 +/- 3.5 microM for Met5-enkephalin and Met5-enkephalin-Arg6-Phe7, respectively). Peptides known to be present within or in close proximity to cerebral vessels (e.g., neurotensin and substance P) competitively inhibited enkephalin degradation (Ki = 20.4 +/- 2.5 and 7.9 +/- 1.6 microM, respectively). These data suggest that cerebral microvascular aminopeptidase M may play a role in vivo in modulating peptide-mediated local cerebral blood flow, and in preventing circulating enkephalins from crossing the blood-brain barrier. PMID- 2879570 TI - Lipids associated with tissue transglutaminase. AB - A substantial amount of lipids (cholesterol and its esters, mono-, di- and triacylglycerols, free fatty acids and the phospholipids phosphatidylethanolamine and phosphatidylinositol) was found associated with tissue transglutaminase purified to apparent homogeneity from guinea pig liver. Removal of lipids results in an increased tendency of the enzyme for self-association and a decreased stability. Lauric acid was detected following hydroxylamine treatment of the enzyme, suggesting the occurrence of a fatty acid-type, covalent, posttranslational modification of transglutaminase. The results provide support for the idea that part of tissue transglutaminase may be localized in the cell membrane. PMID- 2879571 TI - Fetal cardiovascular and breathing movement responses to endogenous opiates. AB - Endogenous opiates have been shown to alter cardiopulmonary activity in a variety of animal models. The present investigation in fetal sheep evaluate the response of heart rate, blood pressure and breathing movements (FBM) to central nervous and intravenous meth-enkephalin and beta-endorphin. Marked bradycardia was noted within 3-5 s of intravenous meth-enkephalin administration and lasted less than 10-15 s. An 84.8 +/- 19.0% prolongation in cardiac cycle length was observed after 20 nmol/kg meth-enkephalin (p less than 0.02). In contrast, there was no significant change in heart rate following 2-50 nmol/kg beta-endorphin. The meth enkephalin-induced slowing of heart rate was virtually eliminated by autonomic blockade with atropine or hexamethonium but merely partially blunted by naloxone. FBM were not altered by intravenous administration of either opiate. However, both meth-enkephalin and beta-endorphin produced a dramatic increase in FBM following injection into the cisterna magna. Prior to opioid administration, FBM were noted 11 +/- 1.4% of the time. Intracisternal opiates resulted in a 43.9 +/- 10.1% incidence of FBM for up to 60 min. Parasympathetic blockade with atropine had no effect on the pattern of FBM following intracisternal opiate administration whereas naloxone terminated the increased respiratory activity within 1 min. These data suggest a potential role for endogenous opiates in the modulation of fetal cardiorespiratory function. PMID- 2879572 TI - [Effect of morphine on the sensitivity of cerebral cortical neurons to acetylcholine]. AB - Sensitivity of sensorimotor cortical neurons to microiontophoretically applied morphine and acetylcholine has been studied in the experiments on unanesthetized rabbits. The predominant reaction to morphine and acetylcholine was decrease and increase in the rate of neuronal impulse activity, respectively. There was no correlation in the responses to morphine and acetylcholine. Atropine failed to influence the morphine effect. When both drugs are simultaneously applied to neurons, morphine decreases both excitatory and inhibitory responses to acetylcholine. This effect of morphine may occur in the case when the drug is applied in doses which do not change spontaneous neuronal activity. On the contrary, excitatory effect of glutamic acid decreased only when morphine was applied in doses causing local anesthetic effect and decreasing background neuronal activity. It is suggested that morphine can exercise a modulating influence on choline receptors of cortical neurons. PMID- 2879573 TI - [Effect of anxiolytics--buspirone and diazepam--on the prolactin, thyrotropin and cortisol content of the blood in the green monkey]. AB - The influence of two anxiolytics--diazepam and buspirone--on prolactin, thyrotrophin and cortisol levels in green monkey (Cercopithecus aethiops) plasma was studied 30 min following i/m injection. Diazepam at 1 mg/kg decreased prolactin and cortisol levels by 30-50% compared to the control animals. Buspirone at 2.5-10 mg/kg induced a 7-10-fold increase in prolactin level but did not change cortisol and thyrotrophin concentration. Buspirone analog--Mj 138-05 at 10 mg/kg produced a 2-3-fold increase in plasma prolactin content in some animals, while at a dose of 5 mg/kg it exerted no detectable effect. Possible neurochemical mechanisms of the effects observed are discussed. PMID- 2879574 TI - [Increased content of nucleotide sequences in transcriptionally active DNA and poly(A)+-mRNA of the rat liver and a rise in its translation activity as affected by inducers]. AB - Cortisol and 3'-methyl-4-dimethyl-amino-azobenzene induce an increase in the content of repeated sequences (RS) in transcriptionally active (TA) DNA, while the content of respective RS in potentially active DNA fractions enriched with regulatory regions of the genome decreases. RS content in induced poly A+-mRNA also rises, as determined by the nature of hybridization of respective c DNA with total DNA. The translation of induced poly A+-mRNA rises essentially, with the qualitative distinctions in in vitro synthesized protein product spectrum being absent. Inducible RS with unstable chromatine conformation are thought to provide a universal system of rapid response of the genetic apparatus to extreme situations, serving as transcription intensifiers in TA DNA and as translation intensifiers in induced poly A+-mRNA. PMID- 2879576 TI - [High interindividual polymorphism in restriction fragment length and copy number of the TURI family of moderate human DNA repetitions]. AB - A human DNA library has been searched for moderate repetitive sequences. Southern's blot analysis of one of the selected clones, which we have termed pTURI-6, has shown a high interindividual restriction fragment length and copy polymorphism. TURI-6 clone can serve as an efficient molecular marker for the identification of interindividual distinctions. PMID- 2879575 TI - [GABA metabolism and the formation of a sensorimotor cortex evoked potential in the presence of excess zinc ions]. AB - Changes in GABA content, the enzymatic activity of its metabolism and the formation of sensorimotor cortical evoked potential (EP) were studied following long-term ZnCl2 administration. It has been established that a single ZnCl2 injection at a dose of 0.1 and 1 mg/kg was accompanied by an increase in the amplitude of sensorimotor cortical EP, though GABA accumulation in this brain structure was observed. This might account for the prolongation of the period of the potential appearance. Long-term (for 7, 14, 21 days) ZnCl2 administration at a dose of 0.1 mg/kg produced a sharp depression in the potential appearance and an increase in GABA content by 50% with the enhancement of glutamate decarboxylase activity and the attenuation of GABA-transaminase activity. PMID- 2879578 TI - [Effect of regulator cells induced by the influenza virus in adoptive transfer]. AB - The protective effect of humoral and cellular immunity factors on experimental mouse influenza infection was studied in combination with a simultaneous analysis of the functional activity in the regulatory lymphocytes of donor mice. The efficacy of adoptive defense of recipient mice, that is the intensity of immune reactions in their organisms, was found to depend on the concrete functional state of donor mouse transferring cells. The exact time of activation of T-helper cells open certain prospects for the concrete pathogenetically grounded drug therapy. PMID- 2879579 TI - Inosine monophosphate dehydrogenase and myeloid cell maturation. AB - In previous studies of purine ribonucleotide metabolism in the human myeloid leukemia cell line HL-60, we observed that there is a down-regulation of guanine ribonucleotide biosynthesis from the central intermediate, inosine monophosphate (IMP) and a depletion of intracellular guanosine triphosphate (GTP) and guanosine diphosphate (GDP) pools that occur during the induced maturation of these cells. We also found that inhibitors of IMP dehydrogenase, the enzyme that catalyzes the first step of guanylate synthesis from IMP, are potent inducers of HL-60 maturation. Because of these observations we specifically investigated the activity of IMP dehydrogenase in HL-60 cells and in a new inducible human myeloid leukemia cell line, RDFD2-25, both during maintenance culture and during induced maturation of the cells. Enzyme activity was examined directly in cell extracts with a radiometric assay that measures free 3H2O formed from [2-3H] IMP during the conversion of IMP to XMP. Uninduced HL-60 and RDFD2 cells in maintenance culture were found to have high levels of IMPD activity (5.2 to 5.7 pmol IMP metabolized/10(7) cells/min) compared with normal neutrophils and monocytes that had been purified from blood (less than 1.5 pmol IMP metabolized/10(7) cells/min). However, when HL-60 and RDFD2-25 cells were induced to mature with retinoic acid (10(-6) mol/L), dimethylformamide (6 X 10(-2) mol/L), or a known IMPD inhibitor, tiazofurin (10(-6) mol/L), IMPD activity in the cells fell by 51% to 80% within three to six hours. These changes in IMPD activity preceded detectable functional and antigenic maturation of the cells by at least 12 hours and were not temporally related to changes in cellular proliferation. These findings are consistent with the concept that the regulation of myeloid cell maturation may be influenced by intracellular concentrations of guanine ribonucleotides because IMP dehydrogenase activity is known to be rate limiting for the production of these nucleotides. PMID- 2879577 TI - [Possible approaches to an analysis of the heterogeneous response of the transcription complex to cholinergic actions]. AB - The accumulation of tyrosine-aminotransferase (TAT) as a marker of the individual gene activation was studied in the rat tissue after the administration of cholinomimetics and cholinolytics in order to elucidate the relations between cholinoreceptor functional state and the genetic apparatus. The regulation of TAT synthesis was found to be controlled by both cholinomimetic concentration and the density of cholinoreceptors in hepatocytes. Transsynaptic regulation of TAT activity was shown to be different in the brain and liver. It is suggested that the approaches discussed might be useful for the analysis of the relationship between cholinoreceptor state and the regulation of biochemical functions of target cells. PMID- 2879580 TI - Mixed chimerism and restriction fragment length polymorphism. PMID- 2879581 TI - Lysosomal arylsulfatases A and B from horse blood leukocytes: purification and physico-chemical properties. AB - Lysosomal arylsulfatases A and B (aryl-sulfate sulfohydrolases, EC 3.1.6.1) from horse leukocytes were purified about 680-fold and 70-fold, respectively, starting from a crude extract of the azurophil and specific granules of leukocytes, by affinity, ion exchange, and gel filtration chromatography. Purified arylsulfatase A displayed anomalous kinetics, a pH optimum at 5.2, an isoelectric point at 4.3, and a Km value for p-nitrocatechol sulfate (pNCS) of 0.37 mM. This enzyme was found to exist in two association states depending on pH: a high molecular weight form at pH 5.0 and a low molecular weight form at pH 7.5. Arylsulfatase B displayed normal kinetics, a pH optimum at 5.8, two isoelectric points at pH 8.6 and 8.9, and a Km value for pNCS of 3.38 mM. The thermostability of the two enzymes was different: arylsulfatase B was found to be more stable than arylsulfatase A. Arylsulfatase A was inhibited by sulfate, sulfite, silver, magnesium, manganese and calcium ions and arylsulfatase B by chloride, sulfate, sulfite and silver ions. PMID- 2879582 TI - Processing of phobic stimuli. AB - The hypothesis tested in the present experiments is that phobics show poor focused attention for phobic stimuli. A test of the hypothesis was undertaken using spider phobics' performance in a recognition memory task involving dead spiders as an index of processing. The first experiment confirmed the hypothesis of poorer processing of spider stimuli in phobics, but only for big spiders on a post hoc division of spider stimuli. These were interpreted as being the more arousing. There was also a tendency for desensitization to improve spider recognition. The second experiment investigated recognition memory under 'ordinary' and 'elaborated' processing conditions, but the hypothesis of poorer spider recognition in phobics was confirmed only in a post hoc correlational analysis for the elaborated processing condition. The hypothesis is related to findings that long-term benefit from exposure treatments is facilitated by focused attention. PMID- 2879583 TI - Venezuelan equine encephalitis virus activity in northern Colombia during April and May 1983. PMID- 2879584 TI - Prejunctional beta-adrenoceptors in rabbit pulmonary artery and mouse atria: effect of alpha-adrenoceptor blockade and phosphodiesterase inhibition. AB - In rabbit isolated pulmonary artery previously incubated with [3H]-noradrenaline, isoprenaline (0.3 microM) had no effect on the stimulation-induced outflow of radioactivity. However, if the phosphodiesterase inhibitor ICI 63,197 (30 microM) or the alpha-adrenoceptor blocker phentolamine (1 microM) was present, then isoprenaline significantly enhanced the stimulation-induced outflow, an effect blocked by propranolol (0.1 microM). ICI 63,197 (30 microM) but not phentolamine significantly enhanced the stimulation-induced outflow of radioactivity. In mouse isolated atria previously incubated with [3H]-noradrenaline and stimulated at a frequency of 10 Hz, isoprenaline had no effect on the stimulation-induced outflow of radioactivity; this is in contrast to its release-enhancing effects at stimulation frequencies of 4 Hz and 2 Hz. The facilitation of stimulation-induced outflow by isoprenaline at 4 Hz was blocked by propranolol (0.08 microM) which, by itself, had no effect on the stimulation-induced outflow. At a stimulation frequency of 2 Hz in mouse atria the facilitatory effect of isoprenaline (0.01 microM) was significantly greater in the presence of ICI 63,197 (30 microM) which, by itself, had no effect on the stimulation-induced outflow. Similarly, the facilitatory effect of isoprenaline was significantly greater in the presence of phentolamine (1 microM) but, in this case, phentolamine significantly enhanced the stimulation-induced outflow. These results suggest that facilitatory prejunctional beta-adrenoceptors are present in both rabbit pulmonary artery and mouse atria. The effects of the phosphodiesterase inhibitor ICI 63,197 suggest that they are linked to adenylate cyclase in both tissues and we propose that the ability of phentolamine to facilitate the release and enhance the effect of isoprenaline may be due to the blockade of alpha-adrenoceptor inhibition of adenylate cyclase. This latter proposition needs further investigation. PMID- 2879585 TI - Pharmacological studies with SK&F 93944 (temelastine), a novel histamine H1 receptor antagonist with negligible ability to penetrate the central nervous system. AB - SK&F 93944 (temelastine), a novel histamine H1-receptor antagonist, has been studied in a variety of in vitro and in vivo test systems. SK&F 93944 was a competitive antagonist of histamine-induced contractions of guinea-pig ileum with a pA2 of 9.55 and a weak, non-competitive, inhibitor of the effects of histamine on guinea-pig atrium. In anaesthetized guinea-pigs SK&F 93944 displaced histamine bronchoconstriction dose-response curves at doses which had negligible effects on histamine tachycardia. In anaesthetized cats SK&F 93944 antagonized depressor responses to the histamine H1-receptor agonists, 2-(2-aminoethyl)pyridine and betahistine, at doses which had no effects on responses to the histamine H2 receptor agonist, dimaprit. Oral pretreatment with SK&F 93944 in conscious rats and guinea-pigs afforded protection versus the response to intradermal histamine injection. Comparative studies in each of the test systems showed that SK&F 93944 was of comparable or significantly greater potency than the standard compound, mepyramine. SK&F 93944 was found to be a weak, non-competitive antagonist of carbachol on the guinea-pig ileum but was devoid of measurable anticholinergic activity in vivo. Studies on the penetration of [14C]-SK&F 93944, labelled either in the isocytosine ring or in the butyl chain, showed that brain concentrations were very low when compared with the steady-state blood concentrations. In contrast, brain concentrations of [3H]-mepyramine exceeded blood concentrations by a factor of approximately 3. SK&F 93944 may have an advantage over classical histamine H1-receptor antagonists in that it is likely to be devoid of untoward effects on the central nervous system. PMID- 2879586 TI - Adrenoceptor blocking properties of atropine-like agents anisodamine and anisodine on brain and cardiovascular tissues of rats. AB - The cholinoceptor antagonists anisodamine and anisodine are widely used in the People's Republic of China for the management of acute circulatory shock but the mechanism of their beneficial effects is not fully known; we therefore investigated if these agents possessed adrenoceptor blocking properties. The antagonistic effect of anisodamine and anisodine against the specific binding of the alpha 1-adrenoceptor ligand [3H]-WB-4101 to cardiac and brain tissue membrane preparations and against the effects of phenylephrine on isolated aortic strips and left atria of rats were compared with classical muscarinic receptor and adrenoceptor blocking agents. Both anisodamine and anisodine possessed alpha 1 adrenoceptor blocking properties; the order of potency of various agents in displacing the binding of [3H]-WB-4101 to receptors and in antagonizing the effects of phenylephrine on aortic strips and left atria was: prazosin greater than atropine greater than anisodamine greater than scopolamine greater than anisodine. It is concluded that both anisodamine and to a lesser extent anisodine possess alpha 1-adrenoceptor blocking properties; this antagonistic activity of anisodamine may contribute to its salutary effects on the microcirculation. However, it is unlikely that anisodine produces a significant adrenoceptor blockade in the clinically used dose-range. PMID- 2879587 TI - Studies on the stereoisomers of beta-adrenoceptor antagonists in conscious A-V blocked dogs. AB - Atrial and ventricular chronotropic effects of the individual stereoisomers of propranolol, pindolol, metoprolol and penbutolol were studied in conscious dogs with chronic atrio-ventricular (A-V) block. Ventricular beta-adrenoceptor blocking activity was assessed for all drugs against isoprenaline under the same experimental conditions. At low doses, the stereoisomers of propranolol and penbutolol decreased atrial rate, whereas those of pindolol and metoprolol produced an increase. At higher doses, all drugs increased atrial rate. All drugs decreased ventricular rate dose-dependently except (+)-pindolol. Relative ventricular beta-blocking potencies of the (-)-isomers of propranolol, pindolol, metoprolol and penbutolol were respectively 38, 21, greater than 43 and 31 times higher than those of their corresponding (+)-isomers. In addition, beta-blocking potencies of (-)- and (+)-pindolol were respectively 60 and 120 times higher, those of (-)- and (+)-penbutolol 7 and 8 times higher and those of (-)- and (+) metoprolol 4 and greater than 4 times weaker than those of (-)- and (+) propranolol. At comparable levels of ventricular beta-adrenoceptor blockade, (-) pindolol and (-)-metoprolol were more potent in producing ventricular bradycardia than their respective (+)-isomers, whereas (-)- and (+)-propranolol and (-)- and (+)-penbutolol were equiactive. In addition, regardless of which isomer was being studied, the order of ventricular bradycardiac potencies, at comparable levels of beta-adrenoceptor blockade, was metoprolol greater than propranolol greater than penbutolol greater than pindolol. In addition, regardless of which isomer was being studied, the order of ventricular bradycardiac potencies, at comparable levels of beta-adrenoceptor blockade, was metoprolol > propranolol > penbutolol >pindolol. 5 These results show that antagonism of beta-adrenoceptors in the ventricle is at least partly responsible for the ventricular bradycardiac effect produced by these drugs, but also that some other factor, apparently distinct from the membrane stabilizing activity, is involved, suggesting the existence of some other as yet unknown pharmacological property of the beta-adrenoceptor blocking drugs, especially evident in metoprolol. Finally, these results demonstrate that the intrinsic sympathomimetic activity exhibited by some of these drugs attenuate their bradycardiac effect. PMID- 2879588 TI - Glutamate-induced increase in intracellular Ca2+ concentration in isolated hippocampal neurones. AB - A system for real-time quantitative monitoring of intracellular free calcium ion concentration ([Ca2+]i) on a single cell basis was developed by the combination of a fluorescent Ca2+ indicator fura-2, a fluorescence microscope, a video-camera and photometrical devices. It was applied to rat individual hippocampal neurones under culture for detection of L-glutamate-induced alterations in the [Ca2+]i level. L-Glutamate (0.01-100 microM) induced a dose-dependent elevation of the [Ca2+]i. The [Ca2+]i in the rat hippocampal neurone was found to be around 30 nM in the resting state, and was increased up to 500 nM by the application of 100 microM L-glutamate. N-methyl-D-aspartate, kainate and quisqualate in a concentration of 10 microM also increased the [Ca2+]i level in the same single neurone, but their efficacy varied between individual cells. The L-glutamate induced [Ca2+]i elevation was abolished after removal of extracellular Ca2+ and was much reduced by Mg2+ (3 mM). The increase was, however, still observed in a Na+-free medium. The L-glutamate-induced [Ca2+]i elevation was not affected substantially after treatment with nitrendipine (10 microM) which blocked the increase in [Ca2+]i induced by an isotonic high KCl-medium (50 mM). The present results suggest that the L-glutamate-induced [Ca2+]i elevation in the hippocampal neurone is due to an influx of Ca2+ through both L-glutamate receptor-coupled and voltage-sensitive ionic channels. PMID- 2879589 TI - Mode of action of (-)-pindolol on feline and human myocardium. AB - (-)-Pindolol antagonized competitively and to a similar extent the positive inotropic effects of both (-)-noradrenaline and (-)-adrenaline in human ventricular preparations. An equilibrium dissociation constant KD (-log mol 1(-1) = pKD) of 9.2-9.3 was estimated regardless of disease present or agonist used. ( )-Pindolol antagonized competitively the positive inotropic effects of (-) adrenaline more than those of (-)-noradrenaline in human atrial preparations. pKD values of (-)-pindolol were 9.6 against (-)-adrenaline and 9.1 against (-) noradrenaline. The results are consistent with a moderate selectivity of (-) pindolol for beta 2-compared to beta 1-adrenoceptors in human atrium. (-) Pindolol competed with [3H]-(-)-bupranolol with a pKD of 9.4 for beta adrenoceptors of human ventricle. Positive inotropic effects of (-)-pindolol were not detected on human atrium or ventricle in a concentration range of 1-1000 nmol 1(-1). The affinity of (-)-pindolol estimated for human myocardial beta adrenoceptors, its moderate beta 2-selectivity and its lack of intrinsic activity for contractile force agreed with similar characteristics in other species. (-) Pindolol caused marked positive chronotropic effects in kitten right atria with an intrinsic activity of 0.5 with respect to catecholamines. On kitten left atria it caused only weak positive inotropic effects with an intrinsic activity of 0.1. (-)-Pindolol (0.6-6000 nmol-1) did not cause positive inotropic effects in kitten papillary muscle. The concentration-effect curve for (-)-pindolol on kitten right and left atria was biphasic. Its positive chronotropic and inotropic effects were not blocked by methysergide, suggesting that 5-hydroxytryptamine (5-HT)-receptors were not involved. Low concentrations of antagonists selective for beta 1- and beta 2-adrenoceptors blocked the high sensitivity component but not the low sensitivity component of the positive chronotropic and inotropic effects. The biphasic nature of the positive chronotropic effects of (-)-pindolol in kitten agreed with previous observations made on guinea-pig right atria and support the concept that 3 receptors in the sinoatrial pacemaker contribute to these chronotropic effects: beta 1, beta 2 and a low-affinity receptor for (-)-pindolol which is neither beta 1 nor beta 2. The partial agonistic activity of (-) pindolol in the heart appears to be mainly (kitten) or completely (man) restricted to the sinoatrial pacemaker. PMID- 2879590 TI - A new class of potent centrally acting muscle relaxants: pharmacology of oxazolidinones in rat decerebrate rigidity. AB - The severity of anaemic decerebrate rigidity was quantitatively determined by measuring the frequency of electromyographic potentials in the rat. Some oxazolidinones markedly reduced the severity of this decerebrate rigidity in a dose-dependent manner, (4S,5R)-4-(2-methylpropyl)-3- [3-(perhydroazepin-1 yl)propyl]-5-phenyl-1,3-oxazolidin-2-on e (MLV-6976) being the most potent. In addition to the oxazolidinones, an aminoalcohol derivative, (1RS,2SR)-5-methyl-1 phenyl-2-(3-piperidinopropylamino )hexan-1-ol (MLV-5860) also reduced the rat decerebrate rigidity. In the oxazolidinone series, the optical isomers with absolute configuration (S) at the 4-position were more potent than the corresponding (4R)-isomers, while there was no significant difference in their LD50 values. Normal rats and mice receiving MLV-6976 at doses which reduced decerebrate rigidity showed no behavioural changes, impairment of motor coordination only appearing at extremely high doses. MLV-6976 and its derivatives did not affect spinal reflex potentials in cats. MLV-6976 reduced the severity of harmaline-induced tremor in mice in a dose-dependent manner, but slightly augmented tremorine-induced tremor. The frequency of the spike discharges induced by iontophoretically applied glutamate was reduced by MLV-6976 in a dose dependent manner in rat cortical neurones. The amplitude of miniature endplate potentials of the rat diaphragm was decreased by MLV-6976 only at concentrations greater than 0.1 mM. It is concluded that MLV-6976 acts on the brainstem or/and higher levels of the brain rather than on the spinal cord or the peripheral nervous system to reduce the excessive activities of the nervous system. PMID- 2879591 TI - Effects of calcium channel antagonists on action potential conduction and transmitter release in the guinea-pig vas deferens. AB - The effects of the Ca2+ channel antagonists amlodipine, cobalt, diltiazem, nifedipine and verapamil and the local anaesthetic lignocaine were investigated on action potential conduction in and on evoked transmitter release from sympathetic nerves in the guinea-pig isolated vas deferens. Transmitter release was investigated by measurement of evoked (trains of pulses at 1 and 2 Hz, 0.1 0.5 ms supramaximal voltage) excitatory junction potentials (e.j.ps) using microelectrodes; tension was recorded simultaneously; tritium [3H] overflow from vasa preincubated (37 degrees C, 30 min) in Krebs solution containing either [3H] noradrenaline (NA, 25 microCi ml-1, 2 X 10(-6) M NA) or [3H]-adenosine (50 microCi ml-1, 1 X 10(-6) M adenosine). Amlodipine (0.5-2 X 10(-4) M), verapamil (0.5-2 X 10(-4) M), diltiazem (1-8 X 10(-4) M), lignocaine (0.1-2 X 10(-3) M) and cobalt (2-6 X 10(-2) M) in descending order of potency, but not nifedipine (1-5 X 10(-3) M), increased the latency and inhibited, then abolished, the amplitude and number of action potentials in a concentration-dependent manner. Amlodipine (0.5 1 X 10(-4) M), verapamil (1-2 X 10(-4) M), diltiazem (1-5 X 10(-4) M) and cobalt (1 X 10(-3) M), in descending order of potency, but not nifedipine (5 X 10(-4) M), inhibited then abolished evoked e.j.ps in a concentration-dependent manner. Cobalt inhibited e.j.ps at a lower concentration than that (2-6 X 10(-2) M) required to block action potential conduction. In unstimulated tissues, the resting [3H] overflow following preincubation with [3H]-NA consisted largely of 4 hydroxy 3-methoxymandelic acid (VMA), 4-hydroxy 3-methoxy phenylglycol (MOPEG), 3,4 dihydroxyphenylglycol (DOPEG) and NA; stimulated tissues (300 pulses at 20 Hz, 0.5 ms supramaximal voltage) released mainly NA. Verapamil (0.1-1 X 10(-4) M), amlodipine (0.05-1 X 10(-4) M) and nifedipine (1-5 X 10(-4) M), but not cobalt (2 X 10(-3) M), increased, significantly, the resting overflow of 3H comprising mainly DOPEG. Cobalt (2 X 10(-3) M) inhibited, significantly, the stimulation-evoked overflow of 3H. Verapamil (1 X 10(-4) M) had little effect on the resting overflow of 3H following preincubation with [3H]-adenosine. Diltiazem (5 X 10(-4) M) and cobalt (2 X 10(-3) M) both inhibited evoked 3H overflow. Nifedipine (5 X 10(-4) M) was ineffective. 6 The effectiveness of Ca2+ channel antagonists at pre- and postjunctional sites differ; the results are discussed in terms of the selectivity of these drugs for each site and their differential effects on transmitter release. PMID- 2879594 TI - Postsynaptic alpha 1- and alpha 2-adrenoceptors in the vascular system of the herring gull, Larus argentatus. AB - The nature of the vascular alpha-adrenoceptors has been studied in the herring gull, Larus argentatus. In the anaesthetized herring gull, both phenylephrine and clonidine elicited dose-dependent increases in arterial blood pressure. The alpha 1-adrenoceptor antagonist prazosin was a better antagonist of phenylephrine than were the alpha 2-adrenoceptor antagonists yohimbine and rauwolscine. Yohimbine and rauwolscine were better antagonists of clonidine than was prazosin. The maximum response to phenylephrine, but not clonidine, was lower in reserpine treated birds, indicating that phenylephrine in high doses liberates endogenous catecholamines, which contribute to the effect. It is concluded that the herring gull possesses postsynaptic, vascular alpha-adrenoceptors, of both the alpha 1- and alpha 2-subtypes, similar to those found in mammals. PMID- 2879592 TI - Alpha-adrenoceptor involvement in catecholamine-induced hyperglycaemia in conscious fasted rabbits. AB - In conscious fasted rabbits an intravenous infusion of phenylephrine (20 micrograms kg-1 min-1) induced hyperglycaemia. The increase in blood glucose was accompanied by a modest increase in insulin secretion and a reduction of liver glycogen. Muscle glycogen and blood lactate levels were not altered by treatment with phenylephrine. Prazosin, 1 mg kg-1 s.c., partially attenuated phenylephrine induced hyperglycaemia. Phenoxybenzamine infusion (16.6 micrograms kg-1 min-1) for 15 min suppressed the increase in blood glucose and the reduction in liver glycogen evoked by phenylephrine. This alpha-adrenoceptor blocker also clearly attenuated the blood glucose elevation observed on infusing adrenaline at 0.3 microgram kg-1 min-1. Blockade by phenoxybenzamine of phenylephrine- and adrenaline-induced hyperglycaemia was not accompanied by a significant increase in immunoreactive insulin plasma levels. Yohimbine infused at a rate of 20 micrograms kg-1 min-1, also completely blocked phenylephrine-induced hyperglycaemia. This suppressor effect was accompanied by a marked rebound in insulin secretion. It is concluded that in normal fasted rabbits stimulation of alpha-adrenoceptors induces hyperglycaemia. The increase in blood glucose depends mainly on liver glycogenolysis and inhibition of insulin secretion. Separate blockade of each component suffices to reduce alpha-adrenoceptor-mediated hyperglycaemia. PMID- 2879593 TI - The effects of alfentanil and selected narcotic analgesics on the rate of action potential discharge of medullary respiratory neurones in anaesthetized rats. AB - The effects of intravenous injections of alfentanil, fentanyl, phenoperidine or morphine on respiratory and peak inspiratory air flow rate, the diaphragm electromyogram (EMG), the activity recorded extracellularly from respiratory neurones located in the ventral respiratory group and the cardiovascular system were examined in anaesthetized rats. Alfentanil produced dose-dependent changes in peripheral and central respiratory parameters, which were prevented by naloxone pretreatment. Minimal effects were produced on the cardiovascular system. The bradypnoea was principally due to a prolongation of the inspiratory phase and was accompanied by a comparable decrease in the peak inspiratory air flow rate. Alfentanil prolonged the discharge duration of inspiratory neurones such that it still maintained a strict phase correlation with the diaphragm EMG, but changes in firing frequency were inconsistent and negligible. The action on expiratory neuronal discharge was analogous to that on inspiratory neuronal discharge but delayed in onset. Hypotension produced by morphine limited the dose used but the respiratory responses to morphine and other selected narcotic analgesics were otherwise similar to that of alfentanil, differing mainly in time course and magnitude. From the respiratory parameters assessed, the order of duration of effect was morphine greater than phenoperidine greater than fentanyl greater than alfentanil and the relative potencies were 0.1, 0.5, 2.5 and 1 respectively. The selective prolongation of inspiration and the immediate action on inspiratory neurones suggests that systemically administered narcotic analgesics may alter the mechanisms within the central respiratory rhythm generator which determine the cessation of inspiration. PMID- 2879595 TI - A comparison between mechanisms of action of different nicotinic blocking agents on rat submandibular ganglia. AB - The blocking properties of tubocurarine, decamethonium, hexamethonium and trimetaphan on nicotinic agonists applied by repetitive ionophoretic pulses were examined in rat submandibular ganglion cells using a two-microelectrode voltage clamp technique at 30 degrees C. Hexamethonium, a proposed slowly dissociating, open-channel blocker at concentrations of 2-20 microM did not produce a 'use dependent' run-down of responses, but its antagonism was clearly dependent on membrane potential. The voltage-dependent reduction of agonist response by hexamethonium was not dependent on the nature of agonist used. Similar results were obtained with acetylcholine (ACh) and carbamylcholine (CCh) ionophoresis. (+)-Tubocurarine (5 microM) and decamethonium (10 microM) produced 'use dependent' run-down of agonist responses which became more pronounced at higher frequency and as the cell was hyperpolarized, consistent with open-channel blockade. In contrast, trimetaphan (2.5 microM), a receptor antagonist did not cause 'use-dependent' run-down of responses. Hence, the antagonism produced by hexamethonium, unlike tubocurarine and decamethonium, could not be accounted for in terms of open-channel blockade but requires an alternative mechanism, the nature of which is discussed. PMID- 2879596 TI - Evidence against VIP as the inhibitory transmitter in non-adrenergic, non cholinergic nerves supplying the longitudinal muscle of the mouse colon. AB - Vasoactive intestinal peptide (VIP) had two types of effects on the longitudinal muscle of the mouse distal colon. At low concentrations (10(-8) M) VIP induced a contraction which seemed to be related to the production of prostaglandins as it was abolished after preincubation with indomethacin (10(-6) M). At higher concentrations (3 X 10(-8) and 10(-7) M) VIP induced relaxations which developed slowly and were related to stimulation of the adenylate cyclase activity of the smooth muscle cells. There is no evidence that VIP is the non-adrenergic, non cholinergic transmitter released by electrical stimulation in this preparation and responsible for rapid relaxation of the smooth muscle. PMID- 2879597 TI - Nicotinic antagonists produce differing amounts of tetanic fade in the isolated diaphragm of the rat. AB - The effects of nicotine antagonists on single twitches, trains of four twitches and tetanic contractions of the isolated diaphragm of the rat were examined. Different drugs were found to produce different amounts of tetanic fade relative to depression of twitch tension. The order of activity from most able, to least able to produce fade was: hexamethonium greater than trimetaphan=atracurium=tubocurarine greater than pancuronium greater than erabutoxin b. The effect of erabutoxin b was distinctive for its almost complete lack of tetanic fade. 3,4-Diaminopyridine increased tetanic fade produced by tubocurarine, atracurium and hexamethonium, but not that produced by erabutoxin b. It is concluded that nicotinic antagonists act at more than one site at the neuromuscular junction. Assuming block of the postjunctional acetylcholine receptor produces tension depression, a second or third site must be involved in producing tetanic fade. The possibility that tetanic fade results from block of the ion channel associated with the postjunctional acetylcholine receptor or from the block of a prejunctional nicotinic receptor is discussed. PMID- 2879598 TI - Cryptorchidism: an apparent substantial increase since 1960. John Radcliffe Hospital Cryptorchidism Study Group. AB - A total of 1849 boys born to mothers resident in a defined area around Oxford were examined for cryptorchidism. Those born in hospital were examined at birth and again after three months if cryptorchid at the earlier examination. The incidence of cryptorchidism at three months adjusted to the birthweight distribution of England and Wales was 1.58%. By comparison, in a very similar study conducted around 1960 the incidence was 0.96%. Hence the cryptorchidism rate had apparently increased by 65% over the two decades, which contrasted with the twofold increase in the national orchidopexy rate. The proportion of boys undergoing orchidopexy appeared consistently to be roughly twice the proportion of boys with an undescended testis at 3 months of age. The increase in cryptorchidism and disparity with the rate of orchidopexy are not easily explained and are the subjects of continuing study. PMID- 2879599 TI - Macrocytic anaemia in patients treated with sulphasalazine for rheumatoid arthritis. PMID- 2879600 TI - Relapse of duodenal ulcer. PMID- 2879601 TI - Treatment of common minor ailments. PMID- 2879603 TI - Failure of carbachol to influence the release of somatostatin from slices of rat cerebral cortex. AB - A [K+]-related, Ca2+-dependent efflux of immunoreactive somatostatin (IRS) from superfused slices of rat cerebral cortex has been observed; this release paralleled the release of both [14C]noradrenaline and [14C]GABA. However IRS release in this preparation was not stimulated by the muscarinic agonist carbachol at low (10 microM) or high (500 microM) concentrations. Furthermore, 100 or 500 microM carbachol did not affect the IRS efflux from rat cortex slices incubated in the presence of 12, 25 or 53 mM K+. PMID- 2879602 TI - Characterization of Na+-dependent binding sites of [3H]glutamate in synaptic membranes from rat brain. AB - Some biochemical characteristics of Na+-dependent binding of [3H]L-glutamic acid (Glu) were studied using crude synaptic membrane preparations from the rat brain as compared with Na+-independent binding. In vitro addition of sodium chloride (1 100 mM) exhibited a significant enhancement of [3H]Glu binding to synaptic membranes in a concentration-dependent manner independent of the incubation temperature employed (2 or 30 degrees C). In contrast, sodium acetate elicited a concentration-dependent augmentation of the binding at 2 degrees C to a significantly greater extent than that found at 30 degrees C. It was found that the binding found in the presence of 100 mM sodium acetate reached its maximal value within 10 min of incubation followed by a rapid decline up to 60 min at 30 degrees C, while gradually increasing up to 60 min at 2 degrees C. The Na+ independent basal binding was significantly activated by the alteration of incubation temperature from 2 to 30 degrees C and reached equilibrium within 10 min of incubation at both incubation temperatures. The Na+-dependent binding was more promptly attenuated by the addition of excess of non-radioactive Glu (1 mM) at 30 degrees C than that at 2 degrees C, whereas the Na+-independent binding was greatly suppressed by the addition at 2 degrees C in comparison with that at 30 degrees C. Quisqualic acid induced a considerably less-potent inhibition of the Na+-dependent binding than that of the Na+-independent binding. Neither N-methyl D-aspartic acid nor kainic acid had such a significant effect on each binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879605 TI - Functional recovery in a rat model of Parkinson's disease following transplantation of cultured human sympathetic neurons. AB - Rats subjected to a unilateral 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal dopamine pathway were given transplants of cultured fetal human sympathetic neurons. Amphetamine-induced turning behavior in these rats was reversed by the transplants after 1.5-4.5 months. The presence of transplanted neurons and their processes was demonstrated by immunohistochemistry for tyrosine hydroxylase. PMID- 2879604 TI - Biochemical evidence for an interaction between adrenaline and noradrenaline neurons in the rat brainstem. AB - In this study, we sought to determine if there was an interaction between the C2 adrenaline-containing (A) neurons of the rat medulla oblongata and the noradrenaline-containing (NA) cell bodies of the locus coeruleus (LC). For this purpose, the biochemical response of the NA cell bodies of the LC after a lesion of the C2 region was studied by using as markers the in vitro activities of the catecholamine synthesizing enzymes: tyrosine hydroxylase (TH), dopamine-beta hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT). An increase in TH activity, not associated with any change in DBH or PNMT activity, was found in the LC (+104%, P less than 0.001) 4 days after a bilateral electrolytic lesion (3 mA for 5 s) of the C2 region. Conversely, the electrolytic lesioning of the neighboring A2 region of NA neurons did not modify the TH activity of the LC. These results suggest the existence of an ascending adrenergic inhibitory control of the NA cell bodies of the LC. PMID- 2879606 TI - Antagonists of glutaminergic neurotransmission block retinotectal transmission in goldfish. AB - The hypothesis that excitatory retinotectal transmission is mediated primarily by a glutamate or glutamate-related transmitter-receptor system was examined by recording extracellular field potentials in isolated sections of goldfish tectum while stimulating the optic tract and applying antagonists of excitatory amino acid (EAA) neurotransmission via the tissue bath. Three antagonists of EAA receptors produced greater than 90% reduction in the postsynaptic components of these evoked potentials. In order of potency, these were (with the concentrations that produced 50% block): kynurenic acid (0.15 mM), gamma-D-glutamylglycine (0.33 mM), and cis-2,3-piperidine dicarboxylic acid (0.47 mM). All 3 log concentration effect curves were parallel, symmetrically sigmoidal, and somewhat steeper than non-cooperative single-site binding isotherms. All antagonist actions stabilized within 15 min and were completely reversible. An EAA antagonist potent and selective for the N-methyl-D-aspartate (NMDA) subtype of receptor, 2-amino-5 phosphonovalerate, had little or no effect in either normal, low [Ca2+]/high [Mg2+], or Mg2+-free media. These data indicate that an excitatory amino acid receptor not of the NMDA subtype plays an essential role in fast excitatory retinotectal transmission, and would be most consistent with the mediation of most or all excitatory retinotectal transmission by a single class and subtype of glutamate receptor. PMID- 2879607 TI - Release of met-enkephalin from rat striatal slices: effect of amphetamine and fipexide. AB - The release of Met-enkephalin immunoreactive material (ME-IR) from rat striatal slices is affected by exposure to amphetamine and fipexide (chloro-4-phenoxy)-2 acetyl-1-(methylene-dioxy 3, 4-benzyl-4-piperazine) a psychostimulant drug with mild dopaminomimetic activity. Both amphetamine and fipexide inhibited in vitro the release of ME-IR. The same effect was observed after in vivo acute administration and is also maintained after chronic treatment. The action of fipexide and amphetamine is still present after reserpine pretreatment. The results indicate that fipexide may facilitate dopamine neurotransmission by inhibition of an enkephalinergic inhibitory feed-back circuit. PMID- 2879608 TI - Glutamate receptor agonists release [3H]GABA preferentially from horizontal cells. AB - A total of 5-6 different cell types in vertebrate retinas accumulate [3H]gamma aminobutyric acid (GABA). In frog retina, specific populations of cells in the horizontal, amacrine and ganglion cell layers are labeled autoradiographically after a 15-min in vitro incubation with [3H]GABA. Cells which may be bipolar or interplexiform cells are also labeled. Similar autoradiographic patterns are observed in chick retina except for the absence of labeled bipolar or interplexiform cells. In rat retinas, [3H]GABA uptake is limited primarily to Muller and amacrine cells. Depolarizing glutamate receptor agonists (glutamate, aspartate and kainic acid) applied in an in vitro perfusion system, stimulated massive release of [3H]GABA from frog and chick retina but not from rat retina. Under these conditions, autoradiographic labeling of horizontal cells was virtually depleted, while labeling of other cell types remained robust. In contrast, potassium caused release of the label from all 3 types of retina, and loss of autoradiographic labeling occurred uniformly in all cell types. We conclude that [3H]GABA-accumulating horizontal cells possess depolarizing glutamate receptors and that activation of these receptors leads to a release of GABA stores. On the other hand, Muller cells and the various subclasses of [3H]GABA-accumulating amacrine, bipolar and/or interplexiform cells, do not release GABA in response to glutamate receptor stimulation and thus appear to be relatively insensitive to excitatory amino acids. PMID- 2879609 TI - Release of growth hormone, prolactin and somatostatin during perifusion of anterior pituitary and preoptic-medial basal hypothalamus from male and female rats. AB - These experiments were designed to determine whether it is possible using in vitro perifusion to identify a sex difference in anterior pituitary (AP) release of growth hormone (GH) and, if so, to determine whether this difference is correlated with a sex difference in hypothalamic release or content of somatostatin (SRIF). Age-matched rats of both sexes were decapitated at approximately 09.00 h, and blood was collected for determination of non-stress plasma concentrations of GH. Each pituitary was rapidly removed and prepared for perifusion of the AP, and each preoptic-medial basal hypothalamus (PO-MBH) was removed and placed in a separate perifusion chamber. The effluent fractions from perifused APs were assayed for GH and prolactin (Prl), and those from PO-MBH blocks were assayed for SRIF. Non-stress plasma GH concentrations were similar in males and females. During perifusion, baseline GH release was higher (P less than 0.001) from male than from female APs. Release of GH from the APs of both sexes was similarly inhibited (P less than 0.001) by a 1-h administration of SRIF (10( 7) M), and high K+ (50 mM) caused larger (P less than 0.05) GH responses from male than from female APs. In contrast, baseline Prl release was higher (P less than 0.01) from female than from male glands, and Prl release was not affected by SRIF. Male and female PO-MBH tissues showed similar baseline release of SRIF and similar responses to high K+. After perifusion, GH content and concentration were higher in APs from males than from females, but SRIF content in the perifused male and female PO-MBH tissues was similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879610 TI - Anxiolytic activity of an endogenous adrenal steroid. AB - The A-ring reduced metabolite of deoxycorticosterone, 3 alpha, 5 alpha tetrahydrodeoxycorticosterone (THDOC) was recently shown to act at the gamma aminobutyric acid receptor-chloride ion channel complex in rat brain. The behavioral profile of THDOC was investigated using two animal models of anxiety, the two-chambered mouse exploration test and the lick suppression conflict test. THDOC showed anxiolytic activity in both animal models, with an anxiolytic dose range, 5-15 mg/kg i.p., separable from the sedative dose range, above 20-30 mg/kg i.p. PMID- 2879611 TI - Regulation of the concentration of dynorphin A1-8 in the striatonigral pathway by the dopaminergic system. AB - The purpose of this study was to explore the dopaminergic control of the striatonigral dynorphin system by measuring the levels of dynorphin A1-8-like immunoreactivity (DN-LI) after repeated injections of a dopaminergic receptor agonist or antagonist. Seven daily injections of different doses of apomorphine (0.5, 1.0, 2.5 and 5.0 mg/kg, s.c.) caused a significant dose-related increase of DN-LI in the striatum (26, 34, 63, 85% over control at each corresponding dose). Similar increases were observed in the substantia nigra (22, 52, 50 and 62% over control). In another experiment, rats received 5 mg/kg of apomorphine for 1, 3, and 7 days. There was a significant time-related increase in DN-LI both in the striatum (37, 50 and 85% over control at each corresponding period) and in the substantial nigra (32, 78 and 62%). Repeated administration of haloperidol (1 mg/kg, i.p.) failed to change the striatal level of DN-LI, but, when given at the same time as apomorphine, significantly attenuated the effect of apomorphine. These results suggest that dopamine exerts a modulatory influence on the metabolism of dynorphin in the striatonigral pathway. PMID- 2879612 TI - Stimulation of hypothalamic beta-endorphin and dynorphin release by corticotropin releasing factor (in vitro). AB - Corticotropin-releasing factor (CRF) at doses of 10(-12)-10(-8) M significantly stimulated the release of beta-endorphin and dynorphin from superfused rat hypothalamic slices. These effects were shown to be mediated by the CRF receptor since they were antagonized by the CRF receptor antagonist alpha-helical CRF9-41 (10(-6) M). The two opioid peptides showed different time courses of response and in the case of beta-endorphin, an attenuation of the response upon continued exposure to CRF was observed. PMID- 2879613 TI - Density and distribution of NMDA receptors in the human hippocampus in Alzheimer's disease. AB - We examined the distribution and density of N-methyl-D-aspartate (NMDA) displaceable L-[3H]glutamate binding sites in human hippocampal samples obtained postmortem from Alzheimer's disease (AD) patients and from age-matched controls. Binding to NMDA receptors was stable for at least 72 h postmortem, and the pharmacological profile corresponded to that described using electrophysiology. NMDA receptors were concentrated in the terminal fields of major hippocampal pathways including the perforant path, Schaffer collaterals and the hippocampal output to the subiculum, all of which are proposed to use an excitatory amino acid transmitter. Little if any change in hippocampal receptor density was observed in AD patients compared to age-matched controls except in one case where major hippocampal cell loss occurred. The distribution of NMDA receptors did, however, correspond to the predilection for neuritic plaques and neurofibrillary tangles in hippocampal subfields. PMID- 2879614 TI - Effect of food deprivation on opioid receptor binding in the brain of lean and fatty Zucker rats. AB - The effect of food deprivation on opioid receptor binding was studied in 6 brain regions of lean and fatty Zucker rats; using [3H]dynorphin A. There was no significant difference between lean and fatty rats fed ad libitum in binding parameters for any regions studied. Food deprivation increased Bmax and/or Kd for cortex, midbrain and striatum of lean rats, and the former two regions of fatty rats. These results suggest that food deprivation may influence opioid receptor binding in lean and fatty Zucker rats. PMID- 2879615 TI - Survival and growth of fetal catecholamine neurons transplanted into primate brain. AB - Dopamine and norepinephrine neuroblasts of the ventral mesencephalon, hypothalamus, and dorsolateral pons were transplanted from fetal African green monkeys into multiple brain sites in adult (host) African green monkeys. Tissue was grafted from both early and late gestational age fetuses. Immunohistochemical analysis, with antibodies to tyrosine hydroxylase, a marker of catecholamine containing neurons, showed large numbers of transplanted catecholamine neurons in host cerebral cortex, corpus striatum and lateral ventricles up to 69 days after transplantation. Serial reconstructions revealed extensive outgrowth of neuronal processes from large numbers of transplanted neurons as well as expansion of the size of transplanted (solid) grafts of fetal brain tissue in the host brain. Some grafts extended from the caudate nucleus into the adjacent lateral ventricles or from the cerebral cortex into the underlying corpus callosum and ventricle. There were dense networks of varicose fibers emanating from the tyrosine hydroxylase positive neurons within intraparenchymal and intraventricular grafts. The size and shape of transplanted neurons retained characteristics common to catecholaminergic neurons from the dissected regions of fetal brain. Thus, a variety of fetal, catecholamine-containing neurons survive transplantation to primate brain and produce extensive neuritic outgrowths. Moreover, rejection of transplanted tissue was not apparent. These findings provide essential information on nerve cell grafting in a species closely related to humans as a prerequisite in the consideration of neural transplants as therapeutic measures in neurological disease. PMID- 2879616 TI - Binding of Tyr-MIF-1 to isolated brain capillaries. AB - Tyr-MIF-1 (Tyr-Pro-Leu-Gly-amide) and the enkephalins have previously been shown with in vivo studies to be transported out of the brain by a saturable, carrier mediated system. The possibility that this transport system occurs at the level of the endothelial cells was tested by measuring the ability of isolated brain capillaries to bind radioiodinated Tyr-MIF-1. The binding of labeled Tyr-MIF-1 was displaced by unlabeled Tyr-MIF-1 (50% inhibition at 1.5 X 10(-6) M) and by nonradioactive (I127) iodinated Tyr-MIF-1, but not by tyrosine, MIF-1 (Pro-Leu Gly-amide), Tyr-Pro, or D-Tyr-MIF-1. This pattern of inhibition is similar to that found for the in vivo transport of Tyr-MIF-1 out of the brain. Tyr-MIF-1 did not appear to be bound by albumin or degraded by cells aged 3-7 days at 4 degrees C. These results suggest that the transport system previously described in vivo for Tyr-MIF-1 and the enkephalins may be associated with the brain endothelial cells. PMID- 2879617 TI - Improved prognosis during and after myocardial infarction: a plea for an integrated and stratified approach. AB - Immediately after the first signs and symptoms of acute myocardial infarction are detected, its prognosis is determined by the size of the area at risk, the availability of collaterals and the time at which interventions are carried out. Preservation of as much myocardial tissue as possible is the key issue. Relief of obstruction of the thrombosed nutrient artery and reperfusion of the myocardium in jeopardy within 4 hours after onset of symptoms can lead to limitation of the ultimate infarct size, maintained ventricular function and a marked reduction of the first year mortality. Early supportive therapy with beta-blockade and calcium antagonists may enhance this effect. Recent data published on 533 patients randomized to either a reperfusion strategy or to conventional therapy, combined with those from the recent literature on thrombolysis and early beta blockade, provide the basis for this point of view. Once infarction is unavoidable and in the process of consolidation, supportive therapy is recommended. This still can change the outcome by timely correction of electrical instability, normalization of afterload and heart-rate, and the avoidance of secondary complications such as peripheral thrombosis. To determine the best course after recovery from the infarction, a symptom limited bicycle stress test, radionuclide ventriculography and 24 hour ambulatory electrocardiogram at the time of discharge were compared in predicting one year survival in 351 hospital survivors. A history of previous myocardial infarction or of heart failure during the current episode proved to be the strongest clinical predictor of early death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879618 TI - Alpha-adrenoceptor blockade and class III antiarrhythmic activity combined: hemodynamic and electrophysiological effects of melperone in the dog. AB - Melperone has been found to possess vasodilating and slight positive inotropic properties in addition to its class III antiarrhythmic action. To determine whether some of these effects might be related to an alpha-adrenoceptor blocking action of melperone, phenoxybenzamine (10 mg/kg) was given as a 2-h infusion to 12 pentobarbital-anesthetized dogs. In addition, six of the dogs were given atenolol 0.5 mg/kg i.v. After a 1-h stabilizing period, melperone (0.5, 2.5, and 12.5 mg/kg) was given i.v. in cumulative doses to both series of dogs. In the presence of alpha-blockade as well as combined alpha- and beta-blockade, atrial, atrioventricular (AV) nodal, and ventricular refractoriness increased and heart rate and AV nodal conduction time decreased, as previously reported after addition of melperone alone. A slight increase in left ventricular (dP/dt)max occurred after the addition of melperone (2.5 mg/kg) in the presence of alpha- and beta-blockade, but only after the highest dose of melperone were small decreases in blood pressure and total peripheral resistance induced. The present study indicates that melperone combines the properties of class III antiarrhythmic action, slight positive inotropy, and alpha-adrenoceptor mediated vasodilation. PMID- 2879619 TI - Desensitization of the vascular contractile response to cumulative doses of alpha 2-adrenoceptor agonists. AB - Contractile responses to single or cumulative doses of alpha-adrenoceptor agonists were compared in the tail artery and the saphenous vein of the rat. In the rat tail artery, there were no differences in the dose-response relationships to noradrenaline, methoxamine, and KCl whether the agonists were applied as single or cumulative doses. However, the responses to single doses of clonidine and B-HT 920 were significantly larger than similar doses applied cumulatively. In the rat saphenous vein, responses to single doses of noradrenaline, clonidine, and B-HT 920 were also significantly larger than the corresponding cumulative doses. However, there was no difference in the responses to KCl. It was suggested that desensitization of alpha 2-adrenoceptors in these vessels may result in the diminished responses to cumulative doses of the agonists. Desensitization appeared to be specific to alpha 2-adrenoceptors, since the effect was not observed in responses mediated by the alpha 1-adrenoceptors and KCl. PMID- 2879620 TI - Neuroleptic potentiation of serum TCA levels is uncommon. PMID- 2879621 TI - Chromosomal location of human P-glycoprotein gene sequences. AB - Nonresponse to chemotherapy may result from the acquisition of multidrug resistance by malignant cells. Overexpression of the 170,000 dalton cell surface P-glycoprotein is associated with this phenotype and this appears to result from amplification of a multigene family coding for this protein. A cDNA encoding a conserved portion of P-glycoprotein has been cloned from hamster cells, and this was used in the present study to localize human P-glycoprotein gene sequences to chromosome 7q36. PMID- 2879622 TI - Effects of microtubule inhibitors on etoposide accumulation and DNA damage in human K562 cells in vitro. AB - The effects of microtubule inhibitors on cellular accumulation of 4' demethylepipodophyllotoxin-9-(4,6-O-ethylidine-beta-D-glu copyranoside) (VP-16) and subsequent epipodophyllotoxin-induced DNA single-strand breaks were investigated in human leukemia K562 cells. At concentrations of 0.05-20 microM, vinblastine, vincristine, and maytansine similarly increased the steady-state cell concentration of VP-16 (2.5 microM) up to 2-fold. Following removal of extracellular vinblastine, the elevation of cell VP-16 was maintained through an additional 55-min incubation period. Washing cells free of extracellular VP-16 resulted in a nonexchangeable (or bound) component comprising 15-17% of the VP-16 concentration found before removal of extracellular drug. In cells incubated with VP-16 alone, removal of extracellular drug resulted in less than 5% cell retention of drug. At vinblastine concentrations of 0.05-0.2 microM, the increase in cell VP-16 was due to a progressive increase in nonexchangeable VP-16. At greater vinblastine concentrations, up to 10 microM, there was no further increase in nonexchangeable VP-16 but there was a 1.6-fold increase in the exchangeable (or free) concentration of VP-16. Similar elevation of both nonexchangeable and exchangeable VP-16 by 10 microM vincristine and maytansine was observed; however, 50-100 microM podophyllotoxin or taxol was required for comparable elevation of exchangeable drug with no increase of nonexchangeable VP 16. Elevation of exchangeable VP-16 in the presence of vinblastine was due to inhibition of the unidirectional efflux of this epipodophyllotoxin with a 69% decline in the rate constant for efflux. There were no effects of vinblastine on VP-16 influx. There was no enhancement of DNA single-strand break frequency when cells were incubated with 2.5 microM VP-16 and 0.2 microM vinblastine, a concentration of the Vinca alkaloid that increased only nonexchangeable VP-16. VP 16-induced DNA damage was enhanced by vinblastine concentrations above 0.5 microM, concentrations that elevated exchangeable VP-16, with a maximum doubling of radiation equivalent single-strand break frequency observed with 20 microM vinblastine, consistent with the maximum elevation of cell VP-16 with 20 microM Vinca alkaloid. These results indicate that vinblastine and other microtubule inhibitors elevate cell VP-16 by inhibition of the efflux of exchangeable drug and by increasing the level of nonexchangeable drug. Potentiation of VP-16 induced DNA damage is observed only at microtubule inhibitor concentrations which elevate exchangeable VP-16.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2879623 TI - Induction of "innocent bystander" cytotoxicity in nonimmune mice by adoptive transfer of L3T4+ Lyt-1+2- mammary tumor immune T-cells. AB - Spleen cells from BALB/c mice, bearing a syngeneic mammary adenocarcinoma, nonspecifically lyse xenogeneic target cells following in vitro reexposure to mammary tumor-associated antigens. The effectors of this reaction have been shown to be Thy-1+ Lyt-1+2+ nylon-adherent cells. Tumor-immune spleen cells are also able to induce nonimmune spleen cells to express nonspecific cytotoxicity. Studies were undertaken to determine whether this inducer activity is mediated by the effector population or by a functionally distinct subset. Cell separation studies demonstrated that the inducers and effectors of innocent bystander cytotoxicity can be separated based upon the property of adherence to nylon wool. Further examination of the nylon-nonadherent inducer population indicated that the phenotype is L3T4 + Lyt-1+2-. By flow cytometry the inducer subset was shown to express a higher density of Thy 1 antigen than that expressed by the cytotoxic effectors. When adult thymectomized mice were implanted with mammary tumors, nonspecific effectors were not generated. In contrast, spleen cells from the same experimental animals were able to induce nonspecific cytotoxicity in normal mice following adoptive transfer of their spleen cells. Thus, these data support the conclusion that during the course of mammary tumor growth, at least two functionally and phenotypically distinct cell populations interact for the expression of "innocent bystander" cytotoxicity. PMID- 2879624 TI - Identification and partial characterization of a Mr 40,000 nucleolar antigen associated with cell proliferation. AB - The present study reports the identification and partial characterization of a novel Mr 40,000 nucleolar antigen (P40) by monoclonal antibodies. Monoclonal antibodies to this protein were obtained when a nucleolar protein extract separated from the immunodominant protein C23 was used to immunize BALB/c mice; 12 hybridoma clones produced antibodies to this protein. P40 was not detected in normal human kidney, liver, and leukocytes but was readily demonstrable in a variety of human malignant tissues. This newly identified P40 antigen differs in its specific nucleolar localization from cyclin (proliferating cell nuclear antigen), a Mr 35,000 antigen which is largely in the nucleoplasm. In addition, cyclin appears in the nucleolus in S-phase; P40 appears in the nucleolus 6 h after refeeding serum-starved HeLa cells. PMID- 2879625 TI - Effects of rat strain, diet composition, and phenobarbital on hepatic gamma glutamyl transpeptidase histochemistry and on the induction of altered hepatocyte foci and hepatic tumors by diethylnitrosamine. AB - To extend our ongoing characterization of modulatory influences on hepatic tumorigenesis, we examined effects of rat strain (Sprague-Dawley versus Fischer), diet composition (semipurified diet versus standard nonpurified laboratory chow), and dietary phenobarbital on the production of gamma-glutamyl transpeptidase (GGT)-positive hepatocyte foci and hepatic tumors initiated by diethylnitrosamine. In addition to GGT-positive foci, we observed, under certain conditions, the appearance of extensive hepatic GGT staining not associated with focal lesions. This elevated nonfocal GGT was found in rats of both strains fed the nonpurified rather than the purified diet, but the level of staining was higher in Fischer than in Sprague-Dawley rats. Enhancement of this nonfocal staining by dietary phenobarbital appeared insignificant. By comparison, frequencies of GGT-positive foci were generally higher in rats fed the semipurified rather than the nonpurified diet, and the frequencies of GGT positive foci were invariably higher in Sprague-Dawley than in Fischer rats. Moreover, dietary phenobarbital generally enhanced focus production. Assessments of focus and tumor yields among these experimental groups showed that differences in focus frequencies did not correspond closely to differences in subsequent tumor formation. These results document the need to consider the influences of diet and rat strain on experimental end points in designing protocols for hepatocarcinogenesis studies, especially those involving GGT histochemistry. The data also raise questions about the mechanistic relevance of GGT induction to hepatocarcinogenesis and support our prior evidence against the putative lineal relationship between foci and tumors. PMID- 2879626 TI - Ifosfamide-induced subclinical tubular nephrotoxicity despite mesna. AB - We monitored acute tubular damage in 16 patients who received a 5-day course of ifosfamide (1.6 g/m2/day) and mesna (1.2 g/m2/day) therapy. Urinary concentrations of alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, and total protein increased in every patient, but the extent of tubular toxicity varied widely among patients. Evidence of toxicity was greatest in patients whose tumors involved the kidneys. The time course of enzymuria and proteinuria indicated tubular cell necrosis. We observed this acute toxic effect despite the administration of sufficient mesna to prevent hemorrhagic cystitis. Urinary marker concentrations returned towards pre-dose levels, and there were no increases in serum creatinine concentrations measured 3 weeks after treatment. PMID- 2879628 TI - Contingent negative variation and efficacy of beta-blocking agents in migraine. AB - Thirty-three patients with common migraine underwent contingent negative variation (CNV) recordings before receiving prophylactic beta-blocker treatment with either metoprolol (27 patients) or propranolol (6 patients) at mean daily dosages of 110 mg and 122 mg, respectively. After 3 months the therapeutic efficacy of the beta-blocker was assessed in each patient by means of a global severity score and compared with the initial CNV recordings. The mean clinical improvement was 62%. A significant positive correlation was found between CNV amplitude before prophylaxis and the clinical response to beta-blockers: patients with higher CNV tended to respond better to therapy. Eight of 10 patients with a CNV amplitude higher than -25 microV had a more than 50% reduction of the severity score--that is, a good or excellent response to the beta-blocking agent- whereas only 2 of 9 patients with an amplitude lower than -20 microV had a good response. PMID- 2879627 TI - Effects of adrenergic and muscarinic receptor stimulation on serum potassium concentrations and myocardial electrical stability. AB - The influence of adrenergic and muscarinic receptor activation on cardiac electrical stability and on serum potassium concentrations was studied in 23 anaesthetised dogs. The ventricular fibrillation threshold was assessed using the single stimulus technique. Adrenaline (1.0 microgram X kg-1 X min-1) caused a brief rise and a subsequent prolonged fall in serum potassium concentration, which was accompanied by a decline in ventricular fibrillation threshold when baroreceptor activation was prevented. After pretreatment with the beta1 adrenoceptor blocking agent metoprolol (0.5 mg X kg-1), adrenaline did not alter vulnerability to ventricular fibrillation but still elicited hypokalaemia. In contrast, selective beta2 adrenoceptor blockade (ICI 118551, 100 micrograms X kg 1) prevented the adrenaline induced lowering of serum potassium concentration but not of ventricular vulnerability. Muscarinic receptor activation by methacholine (3.0 micrograms X kg-1 X min-1) had no effect on serum potassium concentration but increased the ventricular fibrillation threshold by 30%. When methacholine was administered concomitantly with adrenaline the decline in serum potassium concentration persisted, but the increase in ventricular vulnerability was completely prevented. It is concluded that in the normal canine myocardium adrenaline produces an increase in vulnerability that is mediated through beta 1 adrenoceptors and that the beta 2 adrenoceptor mediated hypokalaemia is dissociated from electrophysiological effects of adrenaline. Parasympathetic nervous system activation does not influence serum potassium concentrations but opposes the effects of adrenaline on susceptibility to ventricular fibrillation. PMID- 2879629 TI - Efficacy of beta-blockers in migraine. A critical review. AB - Five double-blind trials of the prophylactic treatment of migraine with beta blockers were reviewed critically with regard to problem investigated, design, "blindness" of patient, side effects, statistical validity, and conclusions. The initial use of a "responder-finding" period may limit the validity of results from a subsequent double-blind crossover placebo-controlled study because it may impair "blindness". A d-propranolol versus racemic propranolol versus placebo study was reanalysed with conventional statistical methods, which showed that d propranolol had no significant effect. In a multicentre study including 96 patients calculation of 95% confidence limits demonstrated that timolol and propranolol are equally effective in common migraine prophylaxis. Metopropolol and propranolol were apparently equally effective in 34 patients, but the calculation of confidence limits showed that a larger study is needed to confirm this conclusion. A group comparison study with three doses of nadolol and placebo lacked statistical evaluation of the results, thereby making it impossible to draw a conclusion about the efficacy of nadolol. It is concluded that there are considerable methodological problems in published papers on beta-blocker and migraine. PMID- 2879630 TI - Beta-adrenoceptor blockade, platelets, and rheologic factors. AB - Alterations in platelet function and other hemorheologic factors have been reported to occur in patients with migraine. The prophylactic treatment of migraine with beta blockers is at present well established, and non-selective as well as beta 1-selective beta blockers exert an effect. The aim of this presentation is to summarize how beta blockers, depending on their receptor selectivity, modulate platelet function and hemorheologic factors. We conclude that non-selective beta blockade increases factors, such as platelet aggregability, and decreases fibrinolytic activity compared with beta 1-selective blockade with metoprolol. These differences do not reflect on their migraine prophylactic effect and indicate that alterations in platelet function are not a primary cause of migraine: rather, they are epiphenomena. PMID- 2879631 TI - Beta-adrenergic effects on cerebral circulation. AB - Noradrenaline, adrenaline, and isoprenaline were infused intracarotidly and the regional cerebral blood flow measured with the intracarotid injection-stationary detector method in patients undergoing carotid angiography. No effect was seen, and beta blockade with intracarotid propranolol also had no effect. The adrenergic effects on cerebral blood vessels are probably neurogenic, and circulating adrenergic agonists and antagonists are unlikely to play a role. Pertubations of adrenergic substances in blood are therefore unlikely to be important in migraine pathophysiology. PMID- 2879632 TI - Beta blockers and the central nervous system. AB - The exact mechanism of action of beta blockers in migraine remains undetermined. An effect on the central nervous system (CNS) might be a factor. The evidence from the literature indicates that the anatomical and chemical targets for these drugs are present in the mammalian brain, that they readily penetrate the brain, and that they may modify CNS functions. The present study shows that psychomotor tests and contingent negative variation (CNV), an event related slow cerebral potential, both of which are abnormal in untreated migraineurs, tend to normalize after treatment with the beta blocker metoprolol. Moreover, a strong positive correlation was found between the amplitude of CNV and the clinical efficacy of beta blockers in migraineurs. One might hypothesize that a hyperactive central catecholaminergic state in migraine might be the common denominator between reduced performance on psychomotor testing and enhanced CNV. It remains to be determined whether this is due to hyperactivity of catecholaminergic neurons or to hypersensitivity of catecholamine receptors. PMID- 2879633 TI - Clinical aspects of beta-blockade. AB - beta-Blocking drugs have no or only a partial beta-agonistic activity (ISA). Since they all bind to beta receptors, they act as competitive inhibitors of the endogenous catecholamines. In addition to this common effect, the beta-blocking drugs also have other properties that may be clinically important, such as extent of beta 1 selectivity, ISA, and lipophilicity. The importance of these properties in the clinical setting is reviewed. PMID- 2879634 TI - Migraine and beta-blockade: modulation of sympathetic neurotransmission. AB - The pathophysiology of both classical and common migraine is still not understood, and there is controversy as to whether the origin is vascular, neuronal, or both. Although the mechanism for the prophylactic effect of beta blockers in migraine has not been elucidated yet, the therapeutic action of beta 1-blockers and non-selective beta-blockers devoid of intrinsic activity is well established by many controlled trials. Mainly on the basis of data from animal experiments, the possible role of central beta-adrenoceptor-mediated mechanisms involved in the control of the activity of noradrenergic neurons will be discussed with reference to migraine. PMID- 2879635 TI - The transforming growth factor-beta system, a complex pattern of cross-reactive ligands and receptors. AB - A new homodimer form of transforming growth factor-beta (TGF-beta), TGF-beta 2, has been identified in porcine blood platelets. TGF-beta 2 is homologous to ordinary TGF-beta (TGF-beta 1), which is also present in platelets. TGF-beta 1.2, a heterodimer containing one TGF-beta 1 chain and one TGF-beta 2 chain, has also been isolated. TGF-beta 1 and TGF-beta 2 interact differently with a family of receptors in target cells. A 280 kd receptor displays high affinity for both TGF beta 1 and TGF-beta 2. Occupancy of this receptor by TGF-beta 1 or TGF-beta 2 correlates with the ability of these TGF-beta s to inhibit cell proliferation. In contrast, 65 kd and 85 kd receptors have high affinity for TGF-beta 1 but lower affinity for TGF-beta 2. The existence of distinct forms of TGF-beta that interact differently with a family of TGF-beta receptors could provide flexibility to the regulation of tissue growth and differentiation by the TGF beta system. PMID- 2879636 TI - Evidence that transforming growth factor-beta is a hormonally regulated negative growth factor in human breast cancer cells. AB - The hormone-dependent human breast cancer cell line MCF-7 secretes transforming growth factor-beta (TGF-beta), which can be detected in the culture medium in a biologically active form. These polypeptides compete with human platelet-derived TGF-beta for binding to its receptor, are biologically active in TGF-beta specific growth assays, and are recognized and inactivated by TGF-beta-specific antibodies. Secretion of active TGF-beta is induced 8 to 27-fold under treatment of MCF-7 cells with growth inhibitory concentrations of antiestrogens. Antiestrogen-induced TGF-beta from MCF-7 cells inhibits the growth of an estrogen receptor-negative human breast cancer cell line in coculture experiments; growth inhibition is reversed with anti-TGF-beta antibodies. We conclude that in MCF-7 cells, TGF-beta is a hormonally regulated growth inhibitor with possible autocrine and paracrine functions in breast cancer cells. PMID- 2879637 TI - Splice commitment dictates neuron-specific alternative RNA processing in calcitonin/CGRP gene expression. AB - The calcitonin/CGRP gene is a complex transcription unit in which developmentally regulated cell-specific alternative RNA processing results in the production of CGRP mRNA in neurons, and of calcitonin mRNA in thyroid C cells. Alternative poly(A) site selection and exon splicing lead to the production of these alternative mature transcripts. The wild-type and a series of mutated calcitonin/CGRP genes were expressed in heterologous cell types, which produced predominantly calcitonin or CGRP mRNA. The results of these studies suggest that neurons express machinery or a factor that determines a specific alternative splicing pathway and consequently its associated alternative poly(A) site selection. It is hypothesized that a splice commitment regulatory factor might modulate pre-mRNA secondary structure, revealing a cryptic splice site required to generate CGRP mRNA in the brain. PMID- 2879638 TI - Regulatory effects of mast cells on lymphoid cells: the role of histamine type 1 receptors in the interaction between mast cells, helper T cells and natural suppressor cells. AB - We have investigated the role of mast cells as modulators of lymphocyte function because the mast cells are concentrated in the areas of lymphoid storage; they are dependent upon T-cell growth factor for their proliferation; and they appear to be the principle if not sole storage site for histamine. We have tested the influence of mast cells on the proliferation of alloreactive cloned helper T cells, mixed leukocyte reactions, and the suppressive capacity of natural suppressor cells. We used an IL-3-dependent mast cell line that at high numbers (greater than 10(5)) suppressed and at low numbers (10(3) to 6 X 10(4)) augmented the proliferation of TH cells. Addition of histamine to cocultures enhanced the mast cell mediated proliferation of TH cells without directly affecting the helper cells. The action of histamine appeared to be mediated with H1 type receptors on these mast cells. Pretreatment of natural suppressor cells with supernatants from mast cell enhanced their suppressive capability. Here too, histamines enhanced suppression by the NS cell via histamine type 1 receptors on the natural suppressor cells. Our data suggest that mast cells may be a major modulator of the lymphoid cell immune function and demonstrate a role of histamine type 1 receptors in the interaction between mast cells, helper T cells, and natural suppressor cells. PMID- 2879639 TI - The influence of dexamethasone treatment on the lymphoid and stromal composition of the mouse thymus: a flowcytometric and immunohistological analysis. AB - The effect of injection of a range of doses of dexamethasone on the distribution of T-cell subpopulations and stromal cells in the thymus of BALB/c mice was investigated with flowcytometry and immunohistology. To this purpose we used monoclonal antibodies directed to the T-cell differentiation antigens Thy-1, T200, Lyt-1, Lyt-2, T4, MEL-14, and monoclonal antibodies directed to various classes of stromal cells. Injection of dexamethasone in increasing doses of 5-130 mg/kg body weight gradually leads to a depletion of the cortical thymocyte population, i.e., bright Thy-1 + ve, dull T-200 + ve, bright Lyt-2 + ve, and bright T4 + ve cells. These cortical cells are very dull MEL-14 + and express variable numbers of Lyt-1 molecules. Also the medulla is affected by dexamethasone although to a lesser extent. Dexamethasone injection at 130 mg/kg selects for a dull Thy-1 + ve, bright T-200 + ve, and bright Lyt-1 + ve medullary population. These cells are either T4 + ve Lyt-2-ve or T4-ve Lyt-2 + ve. Under these conditions, MEL-14 + ve cells were no longer present in the cortex but accumulated in medullary perivascular spaces. Staining of sequential sections showed that this particular subpopulation has a typical "helper" phenotype. This observation provides strong evidence that perivascular compartments are an exit pathway for emigrating T cells. The medullary population contains a phenotypically distinct, dexamethasone-sensitive subpopulation. This conclusion is based on two findings: 130 mg/kg dexamethasone depletes the thymus of all but 4% of the thymocytes, which form a much smaller subpopulation than the population of dull Thy-1 + ve cells (amounting to 15% of the total thymocytes). The medulla contains a subpopulation of dull Lyt-2 + ve cells, which are resistant to 20 mg/kg dexamethasone, but depleted by 130 mg/kg. Dexamethasone also has a severe effect on thymic nonlymphoid cells. Even at low doses, dexamethasone induces TR4 + ve cortical epithelial-reticular cells to become spherical ("nurse cell-like") structures, depleted of lymphoid cells. These stromal cells no longer express MHC antigens in a membrane-bound fashion. In contrast, the medullary epithelial cells appear morphologically unaffected even at a dexamethasone dose of 130 mg/kg. PMID- 2879640 TI - Phenotypic characterization of murine lymphokine-activated killer cells. AB - Short-term culture of murine lymphocytes in interleukin 2 (IL-2), in the absence of any priming antigen, has been shown to result in the differentiation of an activated killer cell population capable of potent cytotoxic activity against tumor cells. The progenitor and lineage of these lymphokine activated killer cells (LAK) remains controversial. The present study was initiated to combine both complement-mediated depletion and flow cytometry to examine the cell surface membrane markers on murine LAK precursors and effectors. Selective depletion of antigen-positive cells from the precursor or effector population followed by functional assays demonstrates that the LAK effector is derived from a non-thymus processed cell (Thy-1 negative). Paradoxically, the effector acquires Thy-1 expression in parallel to the IL-2 induced acquisition of killer cell effector function. These studies clearly show that both precursor and effector cells express the "NK-associated" Qa 5 and asialo GM-1 surface antigens. Mature effectors, but not the precursors, exhibit both Lyt-2 and the "NK-associated" NK 1.1 cell surface marker. Our flow cytometric analyses of murine spleen cells activated in rIL-2 have identified a distinct large, granular cell population which contains the LAK effector. This population, which can be readily discerned using light scattering properties with a flow cytometer, demonstrates both quantitative and qualitative changes in cell surface antigen expression. PMID- 2879641 TI - Polarized microtubule gliding and particle saltations produced by soluble factors from sea urchin eggs and embryos. AB - In this report, we describe an in vitro system for analyzing microtubule-based movements in supernatants of sea urchin egg and embryo homogenates. Using video enhanced DIC microscopy, we have observed bidirectional saltatory particle movements on native taxol-stabilized microtubules assembled in low speed supernatants of Lytechinus egg homogenates, and gliding of these microtubules across a glass surface. A high speed supernatant of soluble proteins, depleted of organelles, microtubules, and their associated proteins supports the gliding of exogenous microtubules and translocation of polystyrene beads along these microtubules. The direction of microtubule gliding has been determined directly by observation of the gliding of flagellar axonemes in which the (+) and (-) ends could be distinguished by biased polar growth of microtubules off the ends. Microtubule gliding is toward the (-) end of the microtubule, is ATP sensitive, and inhibited only by high concentrations of vanadate. These characteristics suggest that the transport complex responsible for microtubule gliding in S2 is kinesin-like. The implications of these molecular interactions for mitosis and other motile events are discussed. PMID- 2879642 TI - [Changes in dipeptidyl peptidase IV activity in the serum of patients with uterine cervix carcinoma before and after therapy]. PMID- 2879644 TI - [Anxiolytics in 1984]. PMID- 2879643 TI - [The effect of oxyprothepine decanoate, lithium and cyproterone acetate on deviant sexual behavior]. PMID- 2879645 TI - [Captopril in the therapy of resistant hypertension in a child with periarteritis nodosa]. PMID- 2879646 TI - [Serological data on hemorrhagic fever with renal syndrome in Southeast Asia]. AB - Using an indirect immunofluorescent test with Hantaan 76-118 and Puumala strains as antigens, antibodies against haemorrhagic fever with renal syndrome viruses were found for the first time in human in Laos and Viet-Nam and confirmed the previously published results in Thailand. These results suggest the existence of an Hantaan-related virus in these countries. PMID- 2879647 TI - [Intestinal parasitic diseases of school children in the Republic of Niger]. AB - Coprologic surveys realized in schoolchildren in a few western areas of the Republic of Niger provided the following results. Concerning protozoa, the prevalence of amebiasis-infestation is strong in all the studies areas, giardiasis is more frequent in dry areas. As for the helminths, Hymenolepsis nana is met everywhere, the prevalence of ancylostomiasis decreases gradually from the south to the north and the endemic area of Schistosoma mansoni is limited to the extreme south of the country. The other helminthiasis are rare. PMID- 2879648 TI - Influence of dietary fat and selenium in initiation and promotion of aflatoxin B1 induced preneoplastic foci in rat liver. AB - Aflatoxin B1-induced hepatic gamma-glutamyl transpeptidase-positive foci were quantified in rats fed different levels of fat and selenium during either initiation or early promotion. Male Sprague-Dawley rats were divided into 12 groups. One of six experimental diets were fed to groups 1-6 prior to and during aflatoxin B1 exposure (initiation, weeks 1-4.5) and to groups 7-12 during weeks 4.5-15 (promotion). The six experimental diets contained 2 or 20% corn oil, each with either less than 0.02, 0.15 or 2.5 (or 1.9) p.p.m. selenium. When not fed the experimental diets, rats were fed a modified AIN-76A diet. In groups 1-6, 0.03% phenobarbital was added as a promoter to the AIN-76A diet. Individual and interactive effects of selenium and fat were dependent on the stage of carcinogenesis. High dietary fat fed with either less than 0.02 or 0.15 p.p.m. selenium during initiation resulted in a significant increase in the number and size of foci when compared with low fat groups. In rats fed 20% fat and 2.5 p.p.m. selenium during initiation, preneoplastic development was reduced below all low fat groups. In contrast, selenium status but not dietary fat level influenced focal formation during promotion. Rats fed less than 0.02 p.p.m. selenium had a significantly greater percentage of liver section occupied by foci than rats fed either 0.15 or 1.9 p.p.m. selenium. Feeding 1.9 p.p.m. selenium during promotion did not afford greater protection above the 0.15 p.p.m. level. Hepatic glutathione peroxidase activity at week 15 was significantly diminished in animals fed less than 0.02 p.p.m. selenium during promotion. Feeding 1.9 p.p.m. selenium when compared with 0.15 p.p.m. did not result in a consistent increase in enzyme activity. Although differences were observed in growth due to dietary treatment, there were no significant correlations between preneoplastic foci and body weight, food consumption or food efficiency. These findings indicate an interaction between dietary fat and selenium during initiation, but not during early promotion. Furthermore, dietary selenium and fat may function by different mechanisms at different stages of carcinogenesis. PMID- 2879649 TI - Sequential histochemical and morphometric studies on preneoplastic and neoplastic lesions induced in rat colon by 1,2-dimethylhydrazine. AB - The sequential histochemical changes during colon carcinogenesis were studied in male Sprague-Dawley rats given 16 weekly subcutaneous injections of 15 mg 1,2 dimethylhydrazine per kg body wt and serially killed at regular intervals. Cryostat sections were used to study the mucus content of the colonic mucosa with the periodic acid Schiff's reaction, and enzyme histochemical methods were applied to investigate the activity of some key enzymes of carbohydrate metabolism at different stages of carcinogenesis. Enlarged mucus-rich crypts with a marked hypercellularity (149% of control as determined morphometrically) appearing very early during carcinogenic treatment revealed almost normal activities of glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Hyperbasophilic crypts lacking mucus production were observed later and showed a loss of G6Pase, but marked increase of G6PDH and GAPDH activity. Mucus-rich signet ring cell carcinomas showed the same enzymatic pattern as the mucus-rich crypts, whereas mucus-free adenocarcinomas and undifferentiated carcinomas revealed a loss of G6Pase and highly increased G6PDH and GAPDH activities. The results showed that focal changes in polysaccharide content and in the activity of some enzymes of carbohydrate metabolism, as observed in various organs, also accompany the carcinogenic process in the colon. This supports the concept that aberrations in carbohydrate metabolism play an important role during the process of carcinogenesis. PMID- 2879650 TI - Comparative effects of smooth and rough Pasteurella hemolytica lipopolysaccharides on arachidonic acid, eicosanoids, serotonin, and histamine in calves. AB - Effect of IV infusions of smooth and rough Pasteurella hemolytica lipopolysaccharides (LPS; 24 ng/kg/min for 500 min) on circulating levels of arachidonic acid, prostaglandins (PG), thromboxane B2 (TxB2), histamine, and serotonin in calves was evaluated. Both smooth and rough LPS had no effects on plasma PGE but caused maximal increases in arachidonic acid, TxB2, and PGF2 alpha at 1 hr and 6-keto-PGF1 alpha at 3 hr of infusion, respectively. The increases in arachidonic acid and its metabolites were greater and more prolonged for smooth LPS than for rough LPS. Although both rough and smooth LPS increased plasma serotonin transiently at 25 min of infusion, only rough LPS decreased serotonin in the later period of endotoxemia. In contrast, smooth, but not rough, LPS decreased plasma histamine during endotoxemia. These results indicate that during endotoxemia there is increased PG and TxA2 synthesis secondary to marked arachidonic acid release into circulation. The data also demonstrate that smooth and rough LPS differ in their abilities to release histamine, serotonin, and eicosanoids. These effects might be due to differences in the in vivo mechanisms of action of smooth and rough LPS and may partly explain the differential potency of smooth and rough LPS in producing pathophysiological changes. PMID- 2879652 TI - [Molecular mechanisms in the pathogenicity of Entamoeba histolytica]. PMID- 2879651 TI - [In vitro effect of tinidazole on Entamoeba histolytica]. PMID- 2879653 TI - Analytical chemistry at the Games of the XXIIIrd Olympiad in Los Angeles, 1984. AB - The equipment, methods, logistics, and results of doping-control analyses for the 1984 Los Angeles Olympic Games are discussed in this article. Within 15 days, 1510 different urine specimens underwent 9440 screening analyses by a combination of gas chromatography, gas chromatography-mass spectrometry, "high-performance" liquid chromatography, and radioimmunoassay. These tests covered more than 200 different drugs and metabolites, including psychomotor stimulants, sympathomimetic amines, central nervous system stimulants, narcotic analgesics, and anabolic steroids. The results are summarized by class of drug. Less than 2% of the samples were found to contain a banned drug. PMID- 2879654 TI - Carrier detection in Duchenne muscular dystrophy: a review of current issues and approaches. AB - The clinical chemistry laboratory has traditionally played a passive role in the application of technology to diagnostic interpretation. Recent developments offer the clinical laboratorian a renewed potential to enter the patient care arena as a consultant. Our lack of understanding of the disease processes in the muscular dystrophies places emphasis on prevention through carrier detection. This review summarizes the clinical progress of the disease, our present understanding of the genetics that control the mode of inheritance of the disease, and the analytical approaches to carrier detection, including their advantages and limitations. Recent advances allow the examination of the genetic material itself instead of concentrating on the phenotypic expression of biochemical abnormalities. PMID- 2879655 TI - Neuropeptide Y in multiple endocrine neoplasia: release during surgery for phaeochromocytoma. AB - High plasma concentrations of neuropeptide Y (NPY) were found in a patient with bilateral adrenal phaeochromocytomas and medullary thyroid carcinoma associated with MEN IIa (32 pmol/l, normal less than 3.5 pmol/l). Both adrenal tumours contained and secreted NPY. Manipulation at operation produced a remarkable increase in plasma NPY concentrations (peak = 1631 pmol/l) coinciding with increases in plasma levels of catecholamines and arterial pressure. NPY was also shown to be present in thyroid tumour tissue: the concentration of NPY in tumour was 50-fold higher (0.9 nmol/g vs 0.004 nmol/g) than in adjacent normal thyroid tissue. It is possible that NPY from some phaeochromocytomas may contribute to hypertension during surgery. PMID- 2879656 TI - Effective long-term treatment of acromegaly with a long-acting somatostatin analogue (SMS 201-995). AB - Nine acromegalic patients, six previously untreated, were studied before and after 3-15 months of treatment with a long-acting somatostatin analogue (SMS 201 995; 100 micrograms injected s.c. three times daily). During treatment, the mean (+/- SEM) 24-h GH concentration fell from 82 +/- 22 mIU/l to 33 +/- 7 mIU/l (P less than 0.001), and eight of the 9 patients showed a reduction of at least 50% in GH levels in the fasting state and/or during a glucose tolerance test. There was a significant 30% fall in serum concentrations of insulin-like growth factor (IGF-1) with SMS. All patients showed rapid clinical improvement, with diminished sweating and headaches, and reduction in skinfold thickness, hand volumes and finger size. Computer tomographic scanning of the pituitary in eight patients showed no change in the size of the pituitary tumour during treatment. The only side-effects of SMS noted were transient abdominal discomfort and loose stools in two patients on initiating therapy. Although fasting plasma glucose concentration did not change during treatment (5.4 +/- 0.3 vs 5.5 +/- 0.3 mmol/l), mean 24-h plasma glucose concentration was higher with SMS (6.6 +/- 0.5 mmol/l vs 6.0 +/- 0.4 mmol/l; P less than 0.02). Mean 24-h plasma insulin concentration fell from 87 +/- 11 mIU/l before treatment to 39 +/- 6 mIU/l during treatment (P less than 0.005). No change in other anterior pituitary hormones was observed. SMS appears to be a safe, rapidly effective, long-term treatment for certain patients with acromegaly. PMID- 2879657 TI - Marfan syndrome: exclusion of genetic linkage to the COL1A2 gene. AB - Marfan Syndrome is a genetic disorder of the connective tissue. Individuals from one large family with this disorder were genotyped for COL1A2 gene associated RFLPs. Our results demonstrated that the COL1A2 gene, encoding the proa2(I) collagen chain, segregated independently of the phenotype and it is therefore excluded as the mutant locus in this family. PMID- 2879658 TI - Immunoglobulin synthesis in myelodysplastic syndromes: normal B-cell and immunoregulatory T-cell functions. AB - Peripheral blood cells from patients with myelodysplastic syndromes were assayed for B-cell and immunoregulatory T-cell functions. The B/T cell ratio in myelodysplastic patients (n = 11) was significantly higher than in controls (n = 12). These patients had a reduction in total T-cell (OKT3+) frequency and in T cell subset (OKT4+/OKT8+) ratios. The response of patients' cells to both pokeweed mitogen (PWM) and phytohemagglutinin (PHA) was reduced, but patients' B cells responded normally to stimulation with Staphylococcus aureus Cowan (SAC). The levels of IgG and IgM detected in 7-day culture supernatants of PWM stimulated patient and control cells were similar. Normal B-cell and immunoregulatory T-cell functions were subsequently demonstrated in allogeneic co culture combinations of enriched T and B cells from patients and controls. The data presented indicate that the frequent infections of myelodysplastic patients are not causally related to impaired humoral mechanisms. The data also favor the possibility that the stem cell disorder in these syndromes is functionally expressed at a subsequent stage to the lymphoid differentiation pathway. PMID- 2879659 TI - Effects of selective and non-selective beta-blockers on the alanine and free fatty acid responses to glucagon challenge in hemodialysis patients. AB - Hypoglycemia is frequently reported in hemodialysis patients on propranolol. The effects of beta-blockers on the glucose, alanine and free fatty acid responses to glucagon challenge (2 mg) in fourteen hemodialysis patients were studied. Patients on propranolol had impaired glycemic response while those on metoprolol had decreased response only before dialysis. There was a significant negative correlation between propranolol level (log-transformed) and glycemic responses, suggesting that propranolol has direct effect on the latter. Hemodialysis patients had fasting alanine levels comparable to those of normal subjects. After glucagon challenge, the decrements in alanine level had no consistent relationship to the impaired glycemic response. Thus suppression of gluconeogenesis is unlikely to be the prime cause of propranolol-induced hypoglycemia. The basal free fatty acid levels were significantly lower among hemodialysis patients on propranolol. This limited availability of free fatty acid as well as the inhibitory effect on hepatic glucagon-stimulated glucose output may contribute to the predisposition to hypoglycemia in dialysis patients given propranolol. The results suggest that metoprolol has less interference on energy substrate supply in hemodialysis patients under fasting conditions. PMID- 2879660 TI - Fatal outcome of aortocoronary bypass grafting in a 62-year-old man with unsuspected coronary arteritis. AB - A 62-year-old man was admitted to our hospital with unstable angina. The coronary arteriography showed the occlusion of the left anterior descending artery and other stenotic lesions. The patient underwent an aortocoronary bypass operation, but unfortunately he did not survive. Surprisingly, the necropsy revealed him to be affected by an inflammatory process, involving the aorta and the coronary arteries. According to the clinical history and examination, the findings at necropsy and the histologic picture, the diagnosis of Takayasu's arteritis appears the most probable. Coronary arteritis has to be considered as a possible etiology of ischemic symptoms also in subjects who appear affected by typical atherosclerotic ischemic heart disease. PMID- 2879661 TI - [Experimental cerebral ischemia effects of fatty acid in Mongolian gerbils]. PMID- 2879662 TI - Pharmacokinetics and pharmacodynamics of esmolol administered as an intravenous bolus. AB - Esmolol is a new ultra-short-acting beta-adrenergic receptor blocking agent that may be useful in the treatment of patients with heart disease. We gave esmolol as an intravenous bolus injection (over 30 seconds) to 12 healthy men in a dose ranging study; each subject received two doses. Our dosing schedule began with 30 mg in the first subject and ended with 100 mg and 150 mg in the final four subjects. We measured blood esmolol concentration, PR interval, QRS duration, QTc interval, cardiac cycle, systolic blood pressure, and diastolic blood pressure. Esmolol doses of 150 mg produced blood esmolol concentrations of 0.868 to 1.47 micrograms/ml. The peak PR interval recorded after esmolol was significantly longer than the control PR interval in four subjects who received 100 and 150 mg doses (192 +/- 7.9 msec vs. 177 +/- 10.6 msec; P = 0.00002). Peak prolongation of the PR interval was recorded 6 to 10 minutes after the bolus, at which time blood esmolol concentrations were negligible. Esmolol did not consistently affect any other pharmacodynamic variable. Giving esmolol as an intravenous bolus injection may be a simple alternative to loading and maintenance infusion in some clinical settings. PMID- 2879663 TI - Enhancement of specific [3H]ouabain binding and ouabain sensitive 86rubidium influx in intact human lymphocytes by a dialysable factor in human and fetal calf serum. AB - We have measured specific [3H]ouabain binding and ouabain sensitive 86rubidium influx in intact human lymphocytes incubated for up to 7 days in media containing different concentrations of fetal calf serum and human serum. Incubation for periods of up to 7 days with fetal calf serum and human serum produced increases in both specific [3H]ouabain binding and ouabain sensitive 86rubidium influx that were dependent on concentration and time. Neither specific [3H]ouabain binding nor ouabain sensitive 86rubidium influx was altered when dialysed serum was used, suggesting that both fetal calf serum and human serum contain a dialysable factor or factors which stimulate specific [3H]ouabain binding and ouabain sensitive 86rubidium influx in intact human lymphocytes. To further elucidate the mechanisms underlying these changes we also measured the activity of two other enzymes of the lymphocyte plasma membrane, 5'-nucleotidase and gamma glutamyltransferase, the uptake of [3H]thymidine by the intact cells, and the effects of cycloheximide, puromycin, and anisomycin, inhibitors of protein synthesis. The activity of 5'-nucleotidase was increased after incubation of the lymphocytes in fetal calf serum for 72 h, but the activity of gamma glutamyltransferase was not changed, suggesting some selectivity of the stimulatory effect. Measurements of [3H]thymidine uptake by the lymphocytes showed that the major part of the observed changes in specific [3H]ouabain binding and ouabain sensitive 86rubidium influx was not attributable to transformation of the lymphocytes to lymphoblasts. All three inhibitors of protein synthesis prevented the increase in specific [3H]ouabain binding due to fetal calf serum. PMID- 2879664 TI - [Systems of pain control as a rationale for drug therapy]. PMID- 2879665 TI - [Clinico-experimental evaluation of clotiazepam on the monitoring status in type I diabetes mellitus with regard to hypoglycemia]. PMID- 2879667 TI - Environmental and sanitary conditions after a cyclone in Tonga. PMID- 2879666 TI - A comprehensive treatment program for schizophrenia and chronic mental illness. AB - The failure of deinstitutionalization and the community mental health movement to improve the treatment of chronic psychiatric patients, particularly schizophrenics, is described. Problems with the current treatment paradigm include unrealistic expectations concerning the rehabilitative effects of antipsychotic medications, inadequate funding of the community mental health system, and the predominance of the "infectious disease model," rather than the more appropriate "chronic disease model" of mental illness. A model for the comprehensive treatment of chronic mental illness is proposed that includes: treatment, rehabilitation, social services, and continuity of care. The need for an integrated community approach to rehabilitating chronic psychiatric patients is stressed, and some of the specific ingredients essential to such a program are identified. PMID- 2879668 TI - A revision of current data and views on membrane hydrolysis and transport in the mammalian small intestine based on a comparison of techniques of chronic and acute experiments: experimental re-investigation and critical review. AB - Literature data and the results of our investigations using both generally accepted and original perfusion techniques of the isolated loop of the rat small intestine in in vivo experiments are reviewed. Significant differences in the functioning of the small intestine under conditions of acute and chronic experiments are revealed. It has been established that in chronic experiments as compared to acute ones: (a) the absorption of glucose, galactose, fructose and glycine is 2-5 times higher; (b) Kt as well as Jmax values of the transport of these nutrients differ considerably; (c) Na+-independent mechanism of glucose and glycine transport predominates; (d) higher rates of membrane hydrolysis and more effective interactions between enzyme and transport systems of the enterocyte brush border membranes are observed; (e) functional characteristics of the small intestine affected by various experimental factors are more stable. The conclusion is made that it is necessary to revise current views of the scale and regularities of digestive-transport processes in the small intestine under physiological conditions. The importance of the suggested approaches for general and comparative physiology and biochemistry is discussed. PMID- 2879669 TI - Circulation during hypoxia in birds. AB - The effects of hypoxia on the avian cardiovascular system are reviewed. The avian cardiovascular system seems well adapted to deal with the stress of hypoxia. In general, birds are remarkably tolerant of hypoxia, with some species being capable of performing vigorous exercise at extreme altitude. During hypoxia at rest, the circulation maintains arterial pressure, increases cardiac output, and redistributes blood flow so oxygen delivery to the heart and brain is maintained. During exercise, further adjustments are required, since exercising muscle has large oxygen requirements. The mechanisms responsible for producing these circulatory changes are largely unknown. The transport steps that limit O2 delivery during hypoxia are also poorly understood. PMID- 2879670 TI - Ontogenetical aspects of nutritional requirements in fish. AB - Changes in morphology i.e. "metamorphosis", mode of respiration, allometric growth of organs, mode of swimming and efficiency of biochemical pathways are briefly reviewed. It is suggested that these processes form the basis for progressive changes in nutrient requirements involving formation and development of several organs, systems and function. Digestive tract morphology changes during ontogenesis and aspects of fish metabolism, protein synthesis rate and body growth rate are interconnected and an attempt is made to explain these processes so as to understand the specificity of larval and juvenile fish nutrient requirements as compared to subadults. Protein and amino acid requirements given the body mass perspective and the generalization of the protein maintenance requirement in protein requirements for maximum growth was estimated to amount to 5-20%. Several cases of amino acid deficiency symptoms showed strong dependence on fish weight (age), but even most numerous studies on salmonids are lacking complete research throughout the life history of one species in defined nutritional and environmental conditions. Larval and juvenile fish have reduced capacity of catabolic adaptability and this fact links them to strictly carnivorous mammals. An attempt is made, for the first time, to relate amino acid needs of fish to young and/or carnivorous mammals. Vitamin requirements of fish are reviewed, taking into account the relationship between body size and time of the first appearance of deficiency symptoms. These are virtually no studies on vitamin requirements in larval warm-water fishes and very few on first feeding salmonids. The same applies to the vitamin need in reproductory fish. Fatty acid deficiencies manifest themselves faster in juvenile fish, but larval fish might require separate classes of lipids, phosphatidylcholine, in the diet to develop and grow at all. It seems that the studies on nutrient requirements have so far not used an ontogenetical perspective, but evidence given throughout this work argues that it would be worthwhile. PMID- 2879671 TI - Response of Japanese quail to hemorrhagic stress after exposure to microwave radiation during embryogeny. AB - Coturnix coturnix japonica eggs were exposed to 2.45 GHz continuous wave microwave radiation at an incident power density of 5 mW/cm2 (SAR = 4 mW/g) during the first 12 days of embryogeny. After hatching, hematologic changes in response to an acute hemorrhage were measured in exposed and nonexposed (control) juveniles and adults of both sexes. Reticulocyte numbers and percentages were depressed below control numbers at 24 hr postphlebotomy in exposed adult females. Lymphocyte numbers were depressed below control levels at 24 hr postphlebotomy in exposed juvenile and adult males. At 72 hr heterophil numbers were depressed in exposed juvenile and adult males. These data suggest that microwave irradiation during embryogeny affects the ability of Japanese quail to recover from an acute and voluminous hemorrhage and that these radiation effects are small. PMID- 2879672 TI - Influence of a "cafeteria" diet on heat production during postnatal development of the rat. AB - Despite different food availability for pregnant rats, the maternal diet had no effect on the weight of the pups at birth. There were no differences in thermogenesis during lactation in pups from dams that received cafeteria diet during pregnancy and after parturition. Both groups of pups grew faster than controls with, however, indistinguishable thermogenesis rates for all pups. After weaning, relative heat production decreased in all groups, even though cafeteria rats showed higher rates than the controls. The higher availability of energetic substrates resulted in increased growth in pups, but only after weaning was the heat output enhanced. PMID- 2879673 TI - Plasma osmolality, urine composition and tissue water content of the toad Bufo viridis Laur. in nature and under controlled laboratory conditions. AB - The compositions of plasma and urine were studied in toads (Bufo viridis) which were collected from three locations in Israel, and compared with toads which were kept under constant laboratory conditions for nearly 2 years. Plasma osmolality was rather constant (over 310 mOsm kg-1 H2O) during the whole year in the active toads. Urea was the most variable osmolyte in the plasma, and accounted for the higher osmolality in southern population. Urine osmolality fluctuated in a circannual fashion both in freshly captured and in the toads under constant laboratory conditions. Water content of the tissues was constant throughout the year, independent of the plasma osmolality. It is concluded that high plasma urea concentration and the excretory system (kidneys and the urinary bladder) are important in sustaining constant plasma osmolality in active toads. Both mechanisms change annually and form the basis for the high terrestriality of this species. PMID- 2879674 TI - Comparative studies of the responses of two strains of rats to an essential fatty acid deficient diet. AB - A comparative study of two strains of rats to an EFA deficient diet was conducted. Parameters of insulin status in BHE and Sprague-Dawley rats were measured. No differences in growth were observed. The strains differed in their hepatic and adipose tissue response to insulin stimulation of glucose oxidation and conversion to fatty acids. Hepatic tissue from EFA deficient BHE rats converted more glucose to fatty acid under the influence of insulin than their controls while diet had no effect on glucose oxidation. Hepatic tissue from EFA deficient Sprague-Dawley rats oxidized more glucose than their controls but diet did not affect fatty acid synthesis. A reverse of these strain and diet differences was observed in adipose tissue. These results suggest that the genetic heritage of the rat may determine the type of response to EFA deficiency. PMID- 2879675 TI - Hepatic bile and pancreatic exocrine secretions evoked by gastrointestinal peptides in sheep. AB - The secretory response of hepatic bile and exocrine pancreas to gastrointestinal peptides has been studied in chronically cannulated sheep. Pancreatic juice flow and protein output were evoked dose dependently by intraportal injection of secretin, CCK-8, caerulein, VIP and neurotensin. However, biliary secretion was evoked by only secretin. Biliary and pancreatic exocrine secretions were enhanced by delivered gastric juice into the duodenum as followed by the increased plasma concentration of immunoreactive secretin (IRS). Results suggest that secretin is the major peptide that regulates pancreatic exocrine secretion and hepatic bile production in the sheep. PMID- 2879676 TI - Development of the gestational plasma hypoaminoacidemia in the rat. AB - The development of the gestational hypoaminoacidemia and the changes in amino acid blood compartmentation have been studied in virgin, 9 day, 12 day and 15 day pregnant rats. The drop of plasma amino acid levels is a rapid phenomenon which takes place between the 9th and the 12th day of pregnancy. It is mainly accounted for by gluconeogenic amino acids. Pregnant rats have lower plasma/cell amino acid ratios than virgin rats. Nine day pregnant rats have lower ratios than controls because of an important increase in the amino acid content of the cell fraction. Twelve and 15 day pregnant rats have lower ratios than controls because of the important drop in plasma levels, since cell content is similar to controls and lower than 9 day pregnant rats. PMID- 2879677 TI - The effect of acclimatization on blood flow and its distribution in normothermic and hyperthermic domestic fowl. AB - Blood flow and its distribution was examined in summer and winter acclimatized normothermic and hyperthermic domestic hens. A clear trend of season on normothermic blood flow distribution was not noted; however, a significant tendency towards increased flow in summer was recorded. In 22 out of 28 organs or tissues examined, blood flow was lower in winter than in summer: pectoral muscle, adrenal and jejunum winter to summer ratios were 36, 64 and 76%, respectively (P less than 0.05). During hyperthermia, blood flow to visceral organ decreased in both groups; in summer this reduction was less severe in parts of the digestive system and more pronounced in parts of the reproductive system. PMID- 2879678 TI - In vitro studies on the release of cortisol from interrenal tissue in trout (Salmo gairdneri)--II. Action of changes in extracellular electrolytes. AB - Secretion of cortisol by the interrenal tissue of the trout Salmo gairdneri was studied in vitro by a perifusion method in relation to the effects of electrolyte concentrations in the medium. An increase in osmotic pressure (produced by adding mannitol or NaCl) induced an immediate, but brief augmentation in cortisol release. Suppression of Na+ had no effect while its reintroduction in the medium led to stimulation of hormone release. By contrast, a sharp peak was obtained whenever Cl- concentration was dropped (by 50 mM fractions). These opposite effects of Na+ and Cl- when they vary independently of each other is interpreted with regard to osmoregulation and acid-base regulation. Raising K+ even to high levels (up to 20 mM) produced no change. The absence of Ca2+ had no obvious effect while its addition induced an immediate peak of cortisol release. In addition, external Ca2+ proved necessary for the action of ACTH to occur. These results establish that cortisol release in trout may be directly affected by changes in electrolyte concentrations in the extracellular space. PMID- 2879679 TI - The short-term effect of prolactin on the active Na transport system of the tadpole skin during metamorphosis. AB - Prolactin (PRL) induced a transient increase in active Na transport measured as the short circuit current (SCC) of the tadpole skin. Increase in SCC by PRL accelerated as the stage advanced between stages XXII and XXV. Prolactin caused two types of effect on the electric parameters of the active Na transport. In type I, it increased both the electromotive force of the active Na current (ENa) and the resistance to the active Na current (RNa). In type II, it decreased both ENa and RNa. A second application of PRL had no effect on SCC; that is, desensitization to PRL was observed. PMID- 2879681 TI - A comparison of three methods for determining the concentration of rat urine. AB - The concentrations of 78 rat urines were compared using osmometry, refractometry and test strips for specific gravity. Test strip specific gravity values are a guide to urine concentration; where small changes of urine concentration are expected, the test strips should not be a replacement for more accurate methods such as osmometry. PMID- 2879680 TI - Streptozotocin treated bullfrogs fail to develop insulin deficiency. AB - Adult Rana catesbeiana and premetamorphic tadpoles were injected with streptozotocin (200-1000 mg/kg, IP). Serum glucose and serum and pancreatic insulin-like immunoreactivity (ILI) were determined at various post injection intervals. Pancreatic beta islet histology or immunocytochemistry was also observed. Bullfrog adults became mildly hyperglycemic after streptozotocin injection but did not develop insulin deficiency. Hyperglycemic frogs had slightly elevated serum ILI concentrations and had pancreatic ILI comparable to that of the controls; hyperglycemic frog islets appeared indistinguishable from control islets. Tadpoles did not respond to streptozotocin. PMID- 2879682 TI - Bioenergetic benefits of huddling by deer mice (Peromyscus maniculatus). AB - Both short photoperiod and communal social living conserve metabolic energy by deer mice held in thermal neutral ambient temperatures. Initial socialization was energetically more costly than solitary living, but huddling behaviors reduced thermal conductance and mass specific metabolic rate by 30% within 5 days. While short photoperiod reduced metabolic energy expenditure by decreasing thermoregulatory demand, huddling mediated behavioral conservation was achieved with hyperthermic core temperatures. PMID- 2879683 TI - Environmentally-related changes in red cell levels of ionic modulators of hemoglobin-O2 affinity in rainbow trout, Salmo gairdneri. AB - Hemoglobin content, plasma and red cell levels of chloride and magnesium and molar ion:hemoglobin ratios were examined in trout acclimatized to eight combinations of two treatment levels of temperature (5, 20 degrees C), O2 availability (less than or equal to 30%, greater than or equal to 75% saturation) and photoperiod (16L:8D, 8L:16D). Increases in hemoglobin content were associated with exposure to higher temperature, abbreviated daylength and hypoxia, with hypoxia greater than photoperiod greater than temperature. Under nominal "summer" conditions (20 degrees C, hypoxia, 16L:8D) photoperiodic influence was apparently masked by hypoxic and thermal effects. Temperature was the principal determinant of plasma and cellular chloride levels as well as [Cl:Hb]. O2 availability and photoperiod had little effect. Temperature was also the primary factor influencing magnesium, with hypoxia exerting a lesser influence. Photoperiod effects were negligible. With increased temperature and reduced O2 availability, plasma magnesium increased white cell magnesium levels and [Mg:Hb] declined. These observations suggest that with normal seasonal changes in environmental conditions, temperature-induced increases in the O2 requirements of summer trout are probably accompanied by increases in blood O2-carrying capacity and reductions in hemoglobin-O2 affinity with consequent increases in O2 delivery to tissues. PMID- 2879684 TI - Characterization of the changes in the state of aggregation induced by ligand binding in the hemoglobin system of a primitive vertebrate, the hagfish Eptatretus cirrhatus. AB - Hemoglobin (Hb) from the hagfish, Eptatretus cirrhatus, is composed of subunits of approx. 20,000 mol. wt. Aggregation of the deoxy subunits occurred, particularly at low pH and at high protein concentration. Oxygen equilibrium studies indicated slight cooperativity and the presence of a small, phosphate independent Bohr effect. Equilibrium properties were protein concentration dependent indicating an oxygen-linked dissociation in the millimolar concentration range. Kinetic studies indicated a dimer to monomer transition in the micromolar concentration range. The ligand-binding character of hagfish Hb was similar to that of lampreys, but was governed by different kinetic and equilibrium parameters. PMID- 2879685 TI - Effects of furazolidone on some reproductive hormones during oestrous cycle in the goat. AB - In non-pregnant goat luteolysis is characterized by a decline in peripheral plasma progesterone level and increased peripheral plasma concentrations of testosterone (T) and 5 alpha-dihydrotestosterone (DHT). Daily oral doses of furazolidone (80 mg/kg) between days 10 and 16 delayed luteolysis and suppressed both the decline in progesterone concentrations and the increase in T and DHT level. PMID- 2879686 TI - Is there functional cholinergic innervation in the frog duodenum (Rana catesbeiana)? AB - To determine if functional cholinergic innervation occurs in the frog duodenum or not, the effects of exogenous acetylcholine and electrical transmural stimulation, the contractile activity of an acid extract from the frog duodenum, and the distribution of acetylcholinesterase (AChE) activity in the wall of the frog duodenum were investigated. Acetylcholine caused non-sustained contraction in a dose-dependent manner (100 nM-1 mM). The ED50 value was 17 +/- 2.4 microM. Atropine (500 nM) shifted the dose-response curve for acetylcholine parallel to the right. Transmural stimulation of the frog duodenum caused frequency-dependent (0.5-50 Hz) contraction which was not decreased by atropine (500 nM) at all. The acid extract from the frog duodenum caused contraction of a longitudinal muscle strip of guinea-pig ileum but atropine (500 nM) had no significant effect on the contraction. Only a little AChE activity was found in Auerbach's plexus of the frog duodenum compared with that of the rat ileum. These results suggest that a cholinergic nerve is present in the frog duodenum but its physiological significance is very small. PMID- 2879688 TI - A comparative study of salivary secretion by parotid and mandibular glands of anaesthetized Capra hircus: effect of pilocarpine. AB - A study was made of basal secretion and the effect of the infusion of pilocarpine on the flow and composition of saliva in the parotid and mandibular glands of the anaesthetized lactating goat. In the parotid gland there was a basal flow (1.6 +/ 0.29 microliter/min) which was not present in the mandibular gland. There is a statistically significant dose-effect relationship between pilocarpine and salivary flow in both glands. Salival composition and its variation with respect to the flow of saliva did not conform to either of the two glands to an exclusive monogastric or ruminant model. PMID- 2879687 TI - Relative zinc-binding activities of ligands in the cytosol of rat small intestine. AB - Relative zinc-binding activities of high-molecular-weight zinc-binding ligand (HMW-ZBL), metallothionein (MT) and low-molecular-weight zinc-binding ligand (LMW ZBL) in the cytosols of rat small intestines under various experimental conditions were examined. Zinc-binding activities of MT decreased and those of LMW-ZBL increased in the intestinal cytosols from most of the experimental rat groups after incubating at 37 degrees C for 2 hr. The relative zinc-binding activity of MT increased with increasing doses of injected zinc and decreased with orally-administered zinc. Isolated MT did not lose zinc-binding activity during incubation at 37 degrees C for 48 hr, but moved from the MT eluting peak to the LMW-ZBL eluting peak after 1 week. PMID- 2879689 TI - De novo biosynthesis of prostaglandins by the Australian field cricket, Teleogryllus commodus. AB - The accumulation and metabolism of certain polyunsaturated fatty acids by testes from the Australian field cricket, Teleogryllus commodus, are described. Testes accumulated a substantial proportion (about 16%) of label from radioactive C20:3n6 that was injected into the haemocoel. Fifty percent of the label accumulated by testes was associated with the phospholipid fraction, whereas in the remainder of the body 30% was incorporated into the phospholipid fraction. Prostaglandins (PG) E1, E2 and F2 alpha were quantified in extracts of the testes of adult insects by radioimmunoassay. Label from injected radioactive C18:2n6, C20:3n6 and C20:4n6 was recovered as prostaglandins PGE and PGF. The radioactivity from C18:2n6 that was recovered as PGE1 and PGF1 alpha indicated elongation/desaturation to C20:3n6 followed by conversion to PG. Since C18:2n6 is readily formed from acetate in T. commodus, these findings indicate the de novo biosynthesis of C20 polyunsaturated fatty acids and prostaglandins by this species. PMID- 2879690 TI - Effects of a perfluorocarbon emulsion, Fluosol-DA, on rat lymphoid tissue and immunological competence. AB - The effects of administration of low doses (5 or 10 ml/kg body wt) of the proprietary perfluorocarbon emulsion blood substitute, Fluosol-DA 20%, on rat lymphoid tissue and antibody production against sheep red blood cells (SRBC) have been studied. Spleen and mesenteric lymph nodes (MLN) were significantly heavier at eight days after injection of Fluosol, whereas liver and thymus weights were unchanged. The mean plasma antibody titre to sheep red blood cells was significantly (P less than 0.05) increased in animals injected intraperitoneally with both doses of Fluosol-DA before immunization. These results show that there are differences in the uptake of perfluorochemicals by certain rat lymphoid tissues and that immunological competence can be altered following administration of such materials. PMID- 2879691 TI - Effects of capsaicin on molluscan neurons: an intracellular study. AB - Effects of capsaicin (CAP) on membrane properties and action potentials (AP) were studied (30-300 microM, at 22 degrees C, pH 7.4) in Helix and Aplysia neurons. CAP (100-300 microM) depolarized the cell membrane and increased the slope resistance. The neuronal firing increased and/or the spike threshold decreased. CAP differentially affected the APs generated in A- and B-cells in Helix or S- and F-cells in Aplysia. Plateau-like prolongation of the APs with a concomitant increase of the hump duration was observed in A-cells, while a significant prolongation of the spike duration was at 90% repolarization time in B-cells. The electrophysiological changes proved to be similar when CAP acted in homologous Helix and Aplysia neurons, but were less pronounced in the latter animal. CAP decreased the rate of rise and the rate of fall of the APs and shortened the action potential duration (APD) in Na-free (TEA) solution. CAP-induced events were dose-dependent and reversible. PMID- 2879692 TI - Effects of capsaicin on molluscan neurons: a voltage clamp study. AB - The effects of capsaicin (CAP) on membrane ionic currents of identified and non identified neurons were investigated by use of the single electrode clamp (SEC). CAP (300 microM, 22 degrees C, pH 7.4) caused a 25-50% reduction of the inward current and a 50-80% reduction of the outward current in normal or Na-free (Tris) solution. The Na current (INa) was moderately decreased (about 10%) in LPa2 neuron, but a 50% reduction of the peak Ca current (ICa) was observed. The action of CAP on ICa varied from cell to cell but an enhanced inactivation of the fast calcium current was found in all neurons studied. CAP (150 microM, 10 min) highly attenuated the long-lasting component of the inward current in LPa2 recorded in Na-free (TEA) Ba solutions. CAP attenuated the fast outward current (IA) and voltage-dependent outward current (IK) in 100 and 300 microM concentrations for the half blocking dose (ID50) in LPa2 neuron, respectively. CAP decreased the slow outward tail currents but hardly influenced the leakage current (IL). We suggest that the acute action of CAP coupled with a series of events in the neuronal membrane can modify the conductance via electrically excitable calcium, potassium and sodium channels differentially. PMID- 2879694 TI - A rapid method for the evaluation of nerve conduction blocking compounds. AB - A simple and easily accessible cockroach nerve preparation is described. Afferent potentials elicited by electric stimulation of the cercus showed remarkable stability, providing a fairly adequate background for pharmacological experimentation. Type I and type II pyrethroids were tested on the nerve preparation, and the results were compared with toxicity data obtained on the same species. Blockade of nerve conduction showed positive correlation (r = 0.804) with lethal effects. The preparation would be useful for determining neuronal point of attack of test compounds and the study of pyrethroids. PMID- 2879695 TI - Seasonal change and sex difference in drug-metabolizing activity in frog liver microsomes. AB - The drug-metabolizing activities (aminopyrine N-demethylase and p-nitroanisole O demethylase activities) have been measured at monthly intervals throughout the year in liver microsomes of male and female Japanese bullfrogs, Rana catesbeiana. The aminopyrine N-demethylase activity based on cytochrome P-450 of both sexes was significantly higher in May-July (spring-summer) than in August-October (summer-autumn). On the contrary, the p-nitroanisole O-demethylase activity based on cytochrome P-450 of males was significantly higher in July-October (summer autumn) than in May-June (spring). However, there was no seasonal changes in the O-demethylase activity in females. There were significant differences between males and females in the N-demethylase activity in August-October and in the O demethylase activity in May-June (or July-October). PMID- 2879693 TI - Influence of calcium lack and nifedipine on carbachol-, potassium- and quinine induced contractions of the lizard isolated rectum. AB - In the lizard isolated rectum, carbachol-, KCl- and quinine-induced contractions were reversibly inhibited by calcium withdrawal. Quinine-induced contractions were more sensitive to calcium lack than were those elicited by carbachol or KCl. Nifedipine inhibited contractile responses induced by all three agonists, but more readily blocked quinine- and carbachol- than KCl-induced contractile responses. It is suggested that extracellular calcium influx stimulated by carbachol, KCl and quinine occurs via different pathways, and that differentiation of calcium channels exists in lizard smooth muscle. PMID- 2879696 TI - Persistence of weight gain and hibernation onset in juvenile thirteen-lined ground squirrels (Spermophilus tridecemlineatus) in spite of long-term administration of naloxone. AB - Sexual differences in body weight of juvenile thirteen-lined ground squirrels (Spermophilus tridecemlineatus) were significant (P less than 0.05) at all weeks of age except weeks 0-4, 6, 7, 9, 20 and 24. Hibernation onset between sexes did not differ significantly. Naloxone administration did not alter weight gain nor onset of hibernation when compared to saline controls. PMID- 2879697 TI - Effects of varying inducer type and dose on hepatic monooxygenase activities in the mountain vole Microtus montanus. AB - Hepatic monooxygenase activities of the mountain vole, Microtus montanus, were measured after i.p. injections of phenobarbital, B-naphthoflavone and Aroclor 1254 at doses ranging from 5 to 80 mg/kg. The results showed that mountain voles differed in their induction of hepatic monooxygenase activity relative to other rodents. The results also suggest substrate specificity in the detection of enzymatic induction and the importance of considering effects of varying inducer doses on hepatic monooxygenases. PMID- 2879698 TI - Histamine-induced hyperphosphatemia and hypocalcemia in the laying hen. AB - The effects of histamine on plasma inorganic phosphorus (Pi) and total calcium values were studied in laying hens during egg formation and in non-laying hens. Histamine induced hyperphosphatemia and slight hypocalcemia during eggshell calcification, whereas the most pronounced hypocalcemia was observed during the early stages of egg formation. The histamine-induced hyperphosphatemia was completely inhibited by cimetidine but only partly by promethazine. However, the histamine-induced hypocalcemia was totally inhibited by cimetidine and promethazine. PMID- 2879699 TI - Propylthiouracil-induced hypothyroid hyperlipidemic chick: a model for clofibrate induced toxicity. AB - An animal model for clinically observed clofibrate (p-chlorophenoxy isobutyrate, CPIB)-induced toxicity has been tested. It is demonstrated that propylthiouracil induced hypothyroid-hyperlipidemic chick develops severe toxic manifestations following clofibrate administration. Toxic symptoms are characterized by listlessness, drowziness, and extreme muscular weakness. This is associated with elevation of blood urea nitrogen, creatine phosphokinase, uric acid and glutamic oxaloacetic transaminase. Histological examination of muscle specimen from chicks exhibiting toxic syndrome showed degeneration and vacuolization of muscle fibers. The biochemical and histological changes observed are quite similar to those reported in clinical practice in some patients given clofibrate. It is suggested that this chick model could be used to investigate the biochemical basis of clofibrate toxicity. PMID- 2879700 TI - Phospholipid dependency of carp brain and liver mitochondrial monoamine oxidase. AB - The effects of lipid-protein interactions on carp brain and liver mitochondrial MAO with respect to substrate and inhibitor preference, thermostability and Arrhenius parameters were studied and compared. Treatment with phospholipase A2, C or D decreased MAO activities towards 5-hydroxytryptamine (5-HT), beta phenylethylamine and tyramine similarly, accompanied by great changes in their apparent affinities for MAO, but not by changes in Vmax values. Minimum phospholipid binding to mitochondria might be essential for enzyme activity. Among these activities, 5-HT deamination was the most sensitive to the changes in mitochondrial phospholipids and bulk lipid phase transition (fluidity). Sensitivity of MAO to clorgyline or l-deprenyl was not affected by these phospholipase treatments. Of the phospholipids tested, only phosphatidylinositol significantly activated MAO activity towards 5-HT in both intact and phospholipase-treated mitochondria. PMID- 2879701 TI - Phosphorus and fluorine NMR examination of the anesthetized newt (Notopthalamus viridescens). AB - We have examined newts by 19F-NMR using the anesthetic halothane as a probe and in another set of experiments taken 31P-NMR spectra under similar conditions. The spectra were recorded from the animal's tail. The water soluble 31P-NMR signals point to little difference between anesthetized and unanesthetized newts except for the potential disappearance of two pools of inorganic phosphate in the anesthetized animals. The 19F spectra show two anesthetic populations in the tail which the phosphorus spectra suggest arise from populations of halothane in muscle and in lipid. PMID- 2879703 TI - Cholinergic antagonists in a solitary wasp venom. AB - The venom of the solitary wasp Philanthus triangulum contains a cholinergic antagonist of the nicotinic receptor of the rectus abdominis muscle of the frog, Xenopus laevis. The venom of African P. triangulum contains two different cholinergic factors, a competitive and a non-competitive antagonist. The venom of the European P. triangulum may not contain a competitive antagonist of the nicotinic receptor of X. laevis, but only a very strong non-competitive antagonist. The possible non-synonymity of both groups of P. triangulum is discussed. PMID- 2879702 TI - Antioxidant enzyme activities and malondialdehyde, glutathione and methemoglobin concentrations in channel catfish exposed to DEF and n-butyl mercaptan. AB - Indicators of free-radical or oxidant-mediated responses were quantified in channel catfish, Ictalurus punctatus, exposed to the organophosphorus herbicide DEF and its metabolite, n-butyl mercaptan (nBM). The activities of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase did not vary significantly with toxicant or dose. The concentrations of reduced glutathione (GSH) and malondialdehyde (MDA) did not vary significantly with toxicant or dose. The percentage of methemoglobin increased in the nBM exposed fish with dose, up to 16.5% of total hemoglobin. The DEF-exposed catfish had no significant increases in methemoglobin compared to controls. PMID- 2879704 TI - Effect of dieldrin injection on the level of certain amino acids and some enzymes in rat brain. AB - The present investigation revealed the effect of the organochlorine insecticide dieldrin at the dose level 0.25 LD50 at different time intervals on the concentration of 11 rat brain amino acids, on the activities of glutamic oxyacetic transaminase (GOT), glutamic pyruvic transaminase (GpT) and cholinesterase. The study was also extended to include the total protein content during the tested periods. The daily injection of dieldrin caused a marked decrease in the levels of glutamic acid, glutamine and taurine and an increase in the levels of aspartic acid, asparagine, GABA, glycine, lysine, serine, alanine and histidine. However, the maximal increase and decrease were recorded for most of the tested amino acids at the end of the tested period. The activity of the transaminases increased significantly. The recorded values of GOT were usually higher than GPT. Cholinesterase activity was inhibited thoroughly during all the experimental periods. Total protein content was decreased in the experiment; the minimal value was given 3 days after the injection. PMID- 2879705 TI - Hormones with adrenocorticotropic and opiate-like activities from the carp (Cyprinus carpio) pituitary. AB - Carp (Cyprinus carpio) pituitary acetone powder was extracted with a mixture of water, hydrochloric acid and acetone. An acid acetone powder was formed by adding the pituitary extract into a large volume of chilled acetone and subsequently recovering the precipitate. The powder was subjected to ion exchange chromatography on CM cellulose. Fractions adsorbed on the ion exchanger exhibited ACTH-like activity as evidenced in the ability to stimulate lipolysis in isolated hamster adipocytes and corticosterone production in isolated rat adrenal decapsular cells and also in cross-reactivity in an ACTH-specific radioimmunoassay. A portion of the ACTH-like bioactivity and immunoactivity was unadsorbed on the ion exchanger. Opiate-like activity in opiate receptor binding assay, employing [3H]D-ala2-D-leu5 enkephalin or [3H]naloxone as ligand, also resided in fractions adsorbed on CM cellulose. The data indicate a separation of ACTH-like and opiate-like activities, and the presence of opiate-like molecules with different affinities of binding to mu and delta opiate receptors. PMID- 2879706 TI - Hydrolysis and protection from hydrolysis of circulating enkephalins. PMID- 2879707 TI - Detection of two TaqI polymorphisms in the VTR region of the human HRAS1 oncogene. AB - Restriction enzyme analysis of the variable tandem repetition (VTR) region of the human HRAS1 oncogene revealed two TaqI polymorphisms. The first polymorphism overlaps that detected with MspI/HpaII restriction enzymes and is due to a variable number of repeat units which form the VTR region at the 3' end of the oncogene. The second polymorphism appears to be due to two new TaqI restriction sites created within the VTR region itself. This novel polymorphism was detected in 26 of 145 human DNA samples and was found to segregate in a Mendelian fashion. PMID- 2879708 TI - Effects of beta-adrenergic agents on hypokalemia. PMID- 2879709 TI - Pathological renal changes in epidemic hemorrhagic fever accompanied by chronic renal failure in one case. PMID- 2879710 TI - Cytogenetic studies of T-leukemia and lymphoma cell lines (MT-1 and HUT-102). Finding of an early duplication region. PMID- 2879712 TI - Some biological properties of virus strains isolated from hemorrhagic fever patients with renal syndrome. PMID- 2879711 TI - Clinical significance of hepatoma-specific band of serum gamma-glutamyl transferase. PMID- 2879713 TI - [Sports: a means of orodental prevention]. PMID- 2879714 TI - [Clinical use of hematopoietic stem cells from fetal livers]. PMID- 2879715 TI - [Epidemiologic studies of the role of cats in the transmission of hemorrhagic fever with renal syndrome (HFRS)]. PMID- 2879716 TI - Effect of somatostatin and thyrotropin-releasing hormone on cholecystokinin induced gallbladder emptying. AB - The effect of somatostatin (0.05 and 1.5 micrograms/kg/hr) and of thyrotropin releasing hormone (0.1 and 1.0 microgram/kg/hr) on cholecystokinin-induced gallbladder emptying was studied in healthy volunteers by means of real-time ultrasonography. In addition, the action of increasing doses (0.05, 0.15, 0.45, and 1.35 micrograms/kg/hr) of somatostatin on resting gallbladder volume was also evaluated. Somatostatin, at the dose of 0.05 microgram/kg/hr (shown to produce blood levels similar to those measured after a meal) significantly inhibited the gallbladder contraction in response to cholecystokinin. Kinetic analysis showed that the interaction of somatostatin and cholecystokinin is of the noncompetitive type. The higher dose of the peptide (1.5 microgram/kg/hr) completely suppressed cholecystokinin-induced gallbladder contraction. In experiments carried out using somatostatin alone, a progressive increase in gallbladder volume in response to increasing doses of peptide was observed. The administration of either dose of thyrotropin-releasing hormone did not affect gallbladder emptying in any of the subjects studied. It is concluded that somatostatin is a potent inhibitor of cholecystokinin action on the gallbladder. The clear effectiveness of a very low, presumably physiological, dose indicates that somatostatin may play a physiological role in the regulation of gallbladder motor activity and provides further evidence that the peptide may act as a true hormone in man. Thyrotropin releasing hormone does not seem to affect gallbladder motility, at least under the experimental conditions of the present study. PMID- 2879717 TI - Gastric acid, plasma gastrin, and somatostatin responses to feeding and exogenous gastrin alone and in combination in conscious cats. AB - Meat in the stomach or duodenum potentiates pentagastrin-induced acid secretion in cats, presumably by a humoral mechanism. In the present study on cats, a meat meal significantly augmented the maximal acid response from a Heidenhain pouch (HP) to pentagastrin or to human synthetic gastrin I by 31 and 30%, respectively. The maximal HP acid response to pentagastrin was augmented also by peptone instilled into the stomach through a gastric fistula. Intravenous infusion of amino acids stimulated acid secretion but did not augment the maximal acid response to pentagastrin. The plasma concentrations of gastrin and somatostatin increased during infusion of pentagastrin and gastrin I and were not further altered by simultaneous feeding. The present results indicate that the mechanism for potentiation of gastrin-induced acid secretion is of physiological significance, since feeding augmented also the acid response to heptadecapeptide gastrin, the only gastrin secreted from the antrum and duodenum in cats. The potentiation of acid secretion is not dependent on the vagal excitation induced by oral feeding, since potentiation was demonstrated also by intragastric peptone instillation. The mechanism for the potentiation is not due to absorbed amino acids or a decrease of plasma somatostatin. PMID- 2879718 TI - A complication of SASP therapy: hair loss. PMID- 2879719 TI - [Choice of beta-blocking agents]. PMID- 2879720 TI - [Treatment of insomnia]. PMID- 2879721 TI - [Clinical value of the determination of TSH-binding inhibitory immunoglobulins (TBII) by a radioreceptor assay]. AB - The aim of the present study was to evaluate the clinical value of a commercial kit for determination of TBII. The study consisted of 50 patients with untreated Graves' disease, 21 patients with Graves' disease before und during medical therapy, 18 patients after finishing medical therapy and 10 patients after surgical treatment. Besides these, 41 patients with other thyroid diseases and 36 patients without any thyroid disorder were included. In 47 (94%) of 50 patients with untreated Graves' disease TBII were detectable in serum using a TSH-standard curve. Binding activities exceeding 10 U/l TSH equivalents were regarded as positive. In other thyroid diseases TBII were negative with the exception of 3 of 22 patient with autonomously functioning thyroid nodules. After 12 months of antithyroid drug treatment of 19 patients the incidence of positive antibody findings was 26%. During follow-up after medical therapy (1-9 years) 7 of 18 patients had increased TBII in correlation with clinical and functional findings. The determination of TBII by TRAK-Assay proved to be a sensitive and specific method. The assay can be used to differentiate between hyperthyroidism of autoimmune or non-immunogenic origin. Even so this method seems to be helpful for the follow-up under medical treatment of patients with Graves' disease. PMID- 2879722 TI - Elevated somatostatin in pancreatic islets of adrenalectomized dogs. AB - We have observed both hyperglucagonemia and hypoinsulinemia in adrenalectomized (Adx) dogs. To determine whether these hormonal alterations are related to changes in distribution of islet hormones in the pancreas, we examined the concentration and total mass of insulin, glucagon, and somatostatin in the head, body, and tail of the pancreas by immunoassay and immunocytochemistry. We studied 6 normal dogs, 5 Adx dogs deprived of cortisol for 24 h (Adx I) and 5 for 48-72 h (Adx II). In normal dogs, single and double immunocytochemical staining showed that, in contrast to some other species, B (insulin) cells are mostly in the central region of islet, whereas A (glucagon) and D (somatostatin) cells are distributed randomly. This topographic distribution was not altered by adrenalectomy. In normal dogs, insulin concentration (micrograms per g) and total mass (micrograms) were higher in the tail (174 +/- 22, 2001 +/- 396) and body (165 +/- 22, 2850 +/- 600) than in the head (91 +/- 17, 668 +/- 156) of pancreas. Glucagon concentration (micrograms per g) and total mass (micrograms) were 17 +/- 2, 178 +/- 17 in the tail; 9.5 +/- 2, 158 +/- 32 in the body, and negligible (0.78 +/- 0.32, 7 +/- 3) in the head, whereas somatostatin concentration (micrograms per g) and total mass (micrograms) were 0.58 +/- 0.26, 4.20 +/- 1.5 in the T, 0.23 +/- 0.10, 3.9 +/- 1.6 in the B, and 0.22 +/- 0.05, 1.8 +/- 0.6 in the H. The striking finding was that adrenalectomy caused large increases in somatostatin in all three regions of pancreas in both Adx I and Adx II. The total mass of somatostatin in Adx I and Adx II increased 4-fold in the tail (P less than 0.02-0.005), 5-fold in the body (P less than 0.01-0.001), and 7-9-fold in the head (P less than 0.05-0.005) and concentration increased 6-fold in the body (P less than 0.005) and 7- to 8-fold in the head (P less than 0.01-0.001). There were no significant changes in the content of insulin and glucagon after adrenalectomy. Plasma concentration of glucagon increased by 50% in Adx I (P less than 0.005) and 70% in Adx II (P less than 0.02), insulin decreased by 39% (P less than 0.005), 23% (NS), respectively, and somatostatin increased by 258% (P less than 0.001) in Adx II. Thus the adrenal glands appear to play an important role in regulation of the content of somatostatin in pancreatic islets. PMID- 2879723 TI - Expression of the prodynorphin gene in male and female mammalian reproductive tissues. AB - Recent studies suggest that opioid peptides may be involved in modulating the hypothalamus-pituitary-gonadal axis at a variety of levels in both males and females. We report here the presence of mRNA coding for the opioid peptide precursor prodynorphin in rat ovary, uterus, and testis. Expression of this opioid peptide precursor gene is compared to expression of two other opioid peptide precursor genes, proenkephalin and proopiomelanocortin, in mammalian reproductive tissues. Immunohistochemical analysis reveals that in the rat testis, prodynorphin-derived peptides are present in Leydig cells. The distribution of dynorphin immunoreactivity in various reproductive tissues was determined. Male reproductive tissues of the rat, rabbit, and guinea pig as well as rat ovary and uterus all contain detectable levels of dynorphin immunoreactivity. These observations suggest that prodynorphin-derived peptides may exert paracrine and/or autocrine effects in mammalian reproductive tissues. PMID- 2879724 TI - Effect of human growth hormone-releasing hormone on the release of dynorphin-like immunoreactivity, luteinizing hormone, and follicle-stimulating hormone from rat adenohypophysis in vitro. AB - The effect of GH-releasing hormone (GHRH) on the release of the endogenous opioid dynorphin from rat adenohypophysis was investigated in vitro. Rat anterior pituitary quarters were incubated in vitro, and hormone release into the incubation medium was measured by RIAs. Human pancreatic GHRH [hpGHRH-(1-44)] as well as human Leu27,Gly45-GHRH [GHRH-(1-45)] enhanced the secretion of dynorphin A1-13-like immunoreactivity (Dyn A1-13-IR) in a concentration-dependent manner. The concentrations of hpGHRH-(1-44) that stimulated the release of Dyn A1-13-IR were about 100-fold higher than those that enhanced GH secretion. GH release induced by hpGHRH-(1-44) was blocked by somatostatin (IC50, approximately 10 nM) without affecting hpGHRH-(1-44)-induced release of Dyn A1-13-IR. GH release was elicited by prostaglandin E2, while Dyn A1-13-IR secretion remained unchanged. At concentrations that enhanced Dyn A1-13-IR release, hpGHRH-(1-44) also elicited LH and FSH secretion. The LHRH antagonist D-pGlu1, D-Phe2,D-Trp3,6-LHRH blocked the secretion of Dyn A1-13-IR, LH, and FSH induced by hpGHRH-(1-44), whereas the LHRH antagonist did not influence the simultaneous GH release elicited by hpGHRH-(1 44). A possible direct effect of GHRH on the LHRH receptor was examined in radioligand binding studies using iodinated D-Ala6, des-Gly10-LHRH ethylamide (LHRH-A). The binding of [125I]iodo-LHRH-A to rat anterior pituitary membranes was completely displaced by hpGHRH-(1-44) and GHRH-(1-45). The deduced apparent dissociation constants were about 3 orders of magnitude higher than that of LHRH A, but were close to those concentrations that enhanced Dyn A1-13-IR release. We conclude that GHRH-induced release of Dyn A1-13-IR is unrelated to GH release. High concentrations of GHRH may interact directly with LHRH receptors on gonadotrophs and thereby enhance the release of LH, FSH, and Dyn A1-13-IR. PMID- 2879725 TI - Basic fibroblast growth factor: production and growth stimulation in cultured adrenal cortex cells. AB - Cultured bovine adrenal cortex cells express the basic fibroblast growth factor (bFGF) gene and contain, but under normal conditions apparently do not release, bFGF. However, once released, bFGF can stimulate proliferation of the cells, indicating that it could act as a self-stimulating growth factor for adrenal cortex cells. It is conceivable that the intracellular bFGF is released upon injury of the adrenal cortex and that it may be involved in the subsequent tissue repair mechanisms by stimulating the proliferation of adrenal cortical and vascular endothelial cells. PMID- 2879726 TI - Microtubules and the gonadotropic regulation of granulosa cell steroidogenesis. AB - The involvement of microtubules in the gonadotropic regulation of granulosa cell steroidogenesis was assessed at the preantral (E2-cells) and antral (PMS-cells) stages of follicular development. The influence of agents that alter microtubule tubulin equilibrium on basal and FSH-stimulated progesterone production was determined in vitro and compared with that on microtubule integrity and organization using immunofluorescence. Basal and FSH-stimulated progesterone production was approximately 2-fold higher in PMS-cells than in E2 cells. Colchicine and nocodazole, two agents that depolymerize microtubules, significantly stimulated progesterone and 20 alpha-hydroxypregn-4-en-3-one production in PMS-cells. Although progesterone production by E2-cells was increased by nocodazole, the amount produced was considerably less than that produced by PMS-cells. FSH-stimulated progesterone biosynthesis was reduced by colchicine and nocodazole in both cell types. Taxol, an agent that stabilizes microtubules, markedly reduced FSH-stimulated progesterone production in both E2- and PMS-cells, but failed to exert a comparable effect on basal steroid production. A close association existed between the concentrations of colchicine, nocodazole, and taxol that altered basal and/or FSH-stimulated steroidogenesis and those that affected microtubule organization and/or distribution. Whereas granulosa cells appeared flattened with numerous cytoplasmic processes after 24 h of culture in medium alone, they were almost spherical and devoid of projections after culture with these agents. FSH-stimulated cells also occupied less area than controls, although cytoplasmic processes were present. These findings indicate an involvement of microtubules in the regulation of granulosa cell steroidogenesis. It is proposed that one of their roles is to facilitate the movement of cholesterol from lipid droplets to mitochondria, possibly by bringing these cellular inclusions closer together. PMID- 2879727 TI - Glucocorticoid receptor-mediated induction of glutamine synthetase in skeletal muscle cells in vitro. AB - We studied the regulation by glucocorticoids of glutamine synthetase in L6 muscle cells in culture. Glutamine synthetase activity was strikingly enhanced by dexamethasone. The dexamethasone-mediated induction of glutamine synthetase activity was blocked by RU38486 [11 beta-(4-dimethylaminophenyl)17 beta-hydroxy 17 alpha-(prop-1-ynyl)estra-4,9-dien-3-one], a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction process. RU38486 alone was without effect. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves increased levels of glutamine synthetase mRNA. Increased enzyme activity was specific for glucocorticoids; other steroid hormones were essentially without effect. The induction of glutamine synthetase was selective, in that glutaminase activity was not induced by dexamethasone treatment of L6 cells. Thus, glucocorticoids regulate the expression of glutamine synthetase mRNA in cultured muscle cells via interaction with intracellular receptors. Such regulation may be relevant to control of glutamine production by muscle. PMID- 2879729 TI - Serum leucine aminopeptidase for monitoring viral infections with plasmacytoid reaction. AB - Analysis of data on 9 cases with active cytomegalovirus infection in patients with kidney grafts showed a positive association of serum leucine aminopeptidase activity concentration with the appearance of plasmacytoid lymphocytes in blood. Additional studies indicate that like the liver, the lymphocytes contain leucine aminopeptidase in relatively large quantities and that this enzyme is increased about 3-fold in plasmacytoid lymphocytes when compared with the activity in normal lymphocytes. In contrast, the 'hepatic' enzyme alanine aminotransferase is practically absent in both lymphocytes and plasmacytoid cells. Therefore, the difference in serum between the relative increases of leucine aminopeptidase and alanine aminotransferase may be attributed to proliferating plasmacytoid lymphocytes. Earlier observations on a large number of cases of acute viral hepatitis A or B lend credence to this assumption. However, in this disease, the serum enzyme changes reflect the much greater involvement of the liver and the relatively slight, but significant, proliferation of plasmacytoid lymphocytes. Our hypothesis is confirmed by the recent observation of 3 cases of acute EBV infection (infectious mononucleosis) in otherwise healthy individuals showing greatly elevated leucine aminopeptidase in contrast to normal or slightly raised alanine aminotransferase in serum. PMID- 2879728 TI - Thyroid status influences rat serum but not brain TRH pyroglutamyl aminopeptidase activities. AB - Serum and brain cytosol contains pyroglutamyl aminopeptidase activity that converts TRH to His-ProNH2 (TRH PAPase). Whereas serum TRH PAPase has specificity for TRH, this is not the case for brain cytosol PAPase. Recent reports indicate that a brain membrane fraction contains TRH PAPase that is specific for TRH and has a remarkable similarity to serum TRH PAPase. In the present studies, a method for measuring serum TRH PAPase activity and the activities of the membrane and cytosol brain TRH PAPase enzymes are described. The effect of thyroid status on these different TRH PAPase activities was determined. In hypothyroid rats serum TRH PAPase activity was decreased, whereas in rats treated with supraphysiological doses of T4 it was increased. In contrast, the cytosolic and the membrane TRH PAPase enzymes in brain were not affected by thyroid status. It is concluded that the membrane-associated brain TRH PAPase differs from the serum TRH PAPase in terms of its response to thyroid hormone. In addition, the previously reported effects of thyroid status on rat serum TRH degrading activity are explained by the finding that thyroid hormone increases serum TRH PAPase activity. PMID- 2879730 TI - Epidemiological features of 5009 cases of equine cryptorchism. AB - Data from 16 North American veterinary university teaching facilities, 5009 cryptorchid horses, were analysed using relative risk methodology. In five breeds (Thoroughbred, Standardbred, Morgan, Tennessee Walking horse and Arabian), cryptorchism was diagnosed significantly (P less than 0.05) less frequently than expected by their representation in the hospital population. Three breeds, (Percheron, American Saddle horse and American Quarterhorse), plus ponies (as a group) and crossbred horses were significantly over-represented within the series. The over-representation of Quarter-horses was evident at each veterinary teaching facility. Other developmental defects and testicular tumours diagnosed in cryptorchid horses were presented. Analysis of the frequency of diagnosis of second anomalies among cryptorchids showed testicular hypoplasia to occur significantly more often, and inguinal and umbilical hernias less often, than expected (P less than 0.05). PMID- 2879731 TI - Fecal colonization with pyelonephritogenic Escherichia coli in neonates as a risk factor for pyelonephritis. AB - The aim of the study was to investigate the properties of fecal P-fimbriated Escherichia coli strains in neonates and to relate these characteristics to the later development of acute pyelonephritis. In a 2 1/2 year prospective study of the children admitted to a particular neonatal ward, 113 children were found to be fecally colonized with a P-fimbriated Escherichia coli strain. However, only one of these children developed pyelonephritis from this strain during the first year of life. The combined results of serotyping, biochemical phenotyping and determination of outer membrane protein pattern as clonal characterization suggested that only 26 of the P-fimbriated strains belonged to a pyelonephritogenic Escherichia coli clone. It is concluded that the risk of a child colonized with an Escherichia coli strain belonging to such a clone of developing pyelonephritis, as calculated in this study, is about 4%. PMID- 2879732 TI - Comparison of specimen transport systems for Bordetella pertussis. PMID- 2879733 TI - Effects of single oral doses of bisoprolol and atenolol on airway function in nonasthmatic chronic obstructive lung disease and angina pectoris. AB - A randomized, placebo-controlled, double-blind crossover investigation in 12 patients with non-asthmatic chronic obstructive lung disease and co-existing stable angina pectoris was done to compare two beta 1-selective adrenoceptor blocking agents, atenolol 100 mg and bisoprolol 20 mg. Systolic and diastolic blood pressures (SBP, DBP), heart rate (HR) as well as airway resistance (AWR, and less frequently forced expiratory volume in 1 s (FEV1) and intrathoracic gas volume (ITGV) were measured in the sitting position before and at various times up to 24 h after drug intake. During the first 4 h both beta-blockers produced a significant reduction in HR in comparison to placebo (p less than 0.01). Atenolol 100 mg significantly increased AWR relative to placebo and bisoprolol (p less than 0.05). After 24 h, a significant reduction in HR (p less than 0.01) could only be demonstrated after bisoprolol, whereas atenolol alone led to a significant elevation in AWR relative to placebo and bisoprolol (p less than 0.05) at that time. It is concluded that bisoprolol appears to have a high degree of beta 1-selectivity, thus providing a wide split between beta 1- and beta 2 adrenoceptor blockade. Bisoprolol in its therapeutic dose range is expected to be relatively safe as regards bronchoconstriction in patients suffering both from hypertension and/or angina pectoris and chronic obstructive lung disease. PMID- 2879734 TI - The assessment of the beta-blocking activity of urapidil: a new method. AB - Urapidil is an antihypertensive vasodilator agent whose pharmacological action in man has not yet been fully defined. We have assessed the beta blocking activity of urapidil 15 mg and 30 mg i.v. in a single blind study of 10 healthy male volunteers. Urapidil at plasma concentrations in the same range as those shown to have antihypertensive affect did not significantly attenuate the chronotropic effect of isoproterenol. Propranolol 5 mg iv, the positive control, significantly shifted the isoproterenol dose-response curve to the right. We describe a new method of analyzing incomplete dose response curves whereby a linear terminal segment can be reproducibly defined. PMID- 2879735 TI - Pharmacokinetics of betaxolol in middle aged patients. AB - The pharmacokinetics of betaxolol was studied in 8 middle-aged (40-60 years) subjects after oral (20 mg) and intravenous (10 mg) administration. The principal parameters were almost identical to those observed in young healthy volunteers. The recommended therapeutic regimen, a single daily dose of 20 mg, appears well suited for middle aged, hypertensive patients. PMID- 2879736 TI - Pharmacologic evaluation of loratadine (SCH 29851), chlorpheniramine and placebo. AB - The antihistaminic effect of loratadine (160 mg) was compared in twenty-four normal male volunteers to chlorpheniramine maleate (4 mg) and placebo in a double blinded 3-way cross-over study of latin square design. After receiving single oral doses of each medication, the wheal response to serial 0.1 ml intradermal histamine (2 micrograms) and saline (control) injections were recorded over a 24 h period. The calculated wheal areas were compared to base-line measurements. The results were analyzed by analysis of variance. Loratadine exhibited a more pronounced inhibition of histamine wheal formation than placebo or chlorpheniramine maleate (p less than 0.003). In contrast to chlorpheniramine maleate which had a duration of action of only 3 h, loratadine inhibited the response for the entire observation period between 1 and 24 h post-dose. Although sedation was observed less frequently with loratadine (Placebo, n = 2; chlorpheniramine, n = 3; and loratadine, n = 1), the relative incidence were not statistically significant. PMID- 2879737 TI - Monoclonal antibodies to a nuclear protein (PCNA/cyclin) associated with DNA replication. AB - Two hybridomas producing monoclonal antibodies to proliferating cell nuclear antigen. (PNCA)/cyclin were generated from spleen cells of BALB/c mice immunized with purified PCNA from rabbit thymus. The specificity of the monoclonal antibodies (19A2 and 19F4) was established by showing that they reacted in enzyme linked immunosorbent assay (ELISA) with purified PCNA. Furthermore, they reacted in one-dimensional (ID) gel immunoblots with a 36 kD polypeptide which also reacted with human autoantibodies from lupus patients. Both monoclonals also recognized the nuclear polypeptide cyclin in two-dimensional (2D) gel immunoblots of HeLa cell proteins. Epitopes recognized by 19A2 and 19F4 were analysed by competitive inhibition test using a modified ELISA. The data suggested that the epitopes were closely related, but not identical. The data with human auto antibodies were more difficult to interpret, although it suggested that some human anti-PCNA may share epitopes with 19A2 and 19F4, but in addition recognize different epitopes on the PCNA molecule. PMID- 2879738 TI - Bombesin-induced hypothermia: possible involvement of cholinergic and dopaminergic receptors in the rat hypothalamus. AB - The thermal responses of rats which were pretreated with 5,7-dihydroxytryptamine to deplete hypothalamic 5-hydroxytryptamine, 6-hydroxydopamine to deplete hypothalamic catecholamines, phentolamine and propranolol to inhibit adrenergic receptors, haloperidol to inhibit dopamine receptors, or atropine to inhibit cholinergic receptors, to intrahypothalamic administration of bombesin were compared with those of control rats. The bombesin-induced hypothermia was attenuated by pretreatment of the rats with either hypothalamic dopamine depletion or receptor blockade, or hypothalamic cholinergic receptor blockade. The reduction in the bombesin-induced hypothermia in the treated rats was due to the reduction of metabolic and vasomotor response. The data indicate that bombesin may act on hypothalamic dopamine and/or cholinergic receptor mechanisms to induce hypothermia by promoting a reduction in metabolic heat production and an enhancement in heat loss in rats. PMID- 2879739 TI - Effect of adriamycin on electron transport in rat heart, liver, and tumor mitochondria. AB - The effect of Adriamycin on mitochondria of the rat heart, liver, and Ehrlich ascites tumor mitochondria has been evaluated. The results may be summarized as follows: Adriamycin reduces both ADP- and FCCP-stimulated respiration, inhibits oxidative phosphorylation, decreases mitochondrial ATP-ase activity, and affects the redox state of respiratory carriers. These alterations are common to all types of mitochondria tested with almost similar patterns. However, the severe cardiotoxicity of the drug cannot be ascribed only to an effect on mitochondrial energy-yielding processes. The addition of hexokinase to phosphorylating heart mitochondria does not increase the sensitivity of succinate oxidation to Adriamycin. Experiments to determine the site of action were not able to detect a specific point of attack. It is conceivable, therefore, that the modifications induced by Adriamycin on the functional parameters of mitochondria may be ascribed to alterations of the physical state of some components of the inner mitochondrial membrane, e.g., lipids, which regulate the kinetic properties of the membrane-associated enzymes. PMID- 2879740 TI - Synthesis of 1,8-naphthyridine derivatives. Potential antihypertensive agents. II. AB - Several 1,8-naphthyridine derivatives have been synthesized and pharmacologically investigated. Some of them exhibited a marked antihypertensive activity on spontaneously hypertensive rats. PMID- 2879741 TI - Oestrogen-induced expression of oncogenes in the immature rat uterus. AB - 4 h after a single precocious administration of oestrogen there was a considerable but short-lived surge in the uterine levels of myc-encoded polyadenylated mRNA. This was followed by a further peak 28 h after hormone administration. The expression of rasHa showed a totally different time course with a build up of hybridizable message that peaked 8 h after oestrogen administration. PMID- 2879742 TI - Membrane translocation and insertion of NH2-terminally anchored gamma-glutamyl transpeptidase require a signal recognition particle. AB - The two subunits of the renal brush border enzyme, gamma-glutamyl transpeptidase (EC 2.3.2.2), are derived from a single-chain propeptide. The membrane-spanning domain consists of a hydrophobic sequence near its NH2-terminus and the protein is oriented with its NH2-terminus on the cytoplasmic side. The enzyme is synthesized without a cleavable signal sequence. Translocation and insertion of this enzyme have been shown to be dependent on the signal recognition particle and presumably require the same translocation machinery that other secretory and membrane proteins use for these processes. PMID- 2879744 TI - Steady-state rate of F1-ATPase turnover during ATP hydrolysis by the single catalytic site. AB - Under the conditions of ATP regeneration and molar excess of nucleotide-depleted F1-ATPase the enzyme catalyses steady-state ATP hydrolysis by the single catalytic site. Values of Km = 10(-8) M and Vm = 0.05 s-1 for the single-site catalysis have been determined. ADP release limits single-site ATP hydrolysis under steady-state conditions. The equilibrium constant for ATP hydrolysis at the F1-ATPase catalytic site is less than or equal to 0.7. PMID- 2879743 TI - Carbon flux through citric acid cycle pathways in perfused heart by 13C NMR spectroscopy. AB - Mathematical models of the TCA cycle derived previously for 14C tracer studies have been extended to 13C NMR to measure the 13C fractional enrichment of [2 13C]acetyl-CoA entering the cycle and the relative activities of the oxidative versus anaplerotic pathways. The analysis is based upon the steady-state enrichment of 13C into the glutamate carbons. Hearts perfused with [2-13C]acetate show low but significant activity of the anaplerotic pathways. Activation of two different anaplerotic pathways is demonstrated by addition of unlabeled propionate or pyruvate to hearts perfused with [2-13C]acetate. In each case, the amount of [2-13C]acetate being oxidized and the relative carbon flux through anaplerotic versus oxidative pathways are evaluated. PMID- 2879745 TI - Primary structure of the biotin-binding site of chicken liver acetyl-CoA carboxylase. AB - Limited proteolysis of chicken liver acetyl-CoA carboxylase by staphylococcal serine proteinase yielded a fragment of 31 kDa which contained the biotinyl active site. This polypeptide was purified by preparative polyacrylamide gel electrophoresis and characterized. The complete amino acid sequence of this polypeptide has been deduced from the nucleotide sequence of cloned DNA complementary to the chicken liver acetyl-CoA carboxylase mRNA. A highly conserved sequence of Met-Lys-Met was found in the biotin-binding site. Appreciable homology was observed among the sequences in close vicinity of the biotin sites of chicken liver acetyl-CoA carboxylase and other biotin-dependent carboxylases including biotin carboxyl carrier protein of Escherichia coli acetyl CoA carboxylase. PMID- 2879746 TI - Catecholaminergic primary sensory neurons: autonomic targets and mechanisms of transmitter regulation. AB - Contrary to traditional teaching, mammalian primary sensory neurons may express catecholaminergic (CA) neurotransmitter characteristics in vivo. Sensory neurons in the nodose, petrosal, and dorsal root ganglia of rats express tyrosine hydroxylase, the rate-limiting enzyme in CA biosynthesis, and formaldehyde induced CA fluorescence, in addition to other CA traits. These findings suggest that catecholamines may function as sensory as well as autonomic motor (e.g., sympathetic) neurotransmitters. Most CA cells in the petrosal ganglion project peripherally to the carotid body, which indicates a striking correlation between CA expression in sensory neurons and the pattern of sensory innervation. Inasmuch as petrosal ganglion afferents make synaptic contact with chemoreceptive glomus cells in the carotid body, it is likely that CA sensory neurons in the ganglion transmit chemoreceptor information to the brain stem. Comparison with sympathetic neurons indicates that some mechanisms of CA regulation, such as altered activity of tyrosine hydroxylase in response to depolarizing stimuli, are shared among sensory and traditional CA populations. Other mechanisms, including trophic regulation, appear to be distinct. Therefore, despite expression of common phenotypic traits, CA expression in diverse populations of peripheral neurons is not necessarily associated with a common repertoire of regulatory mechanisms. PMID- 2879747 TI - [Organization of alcohol abuse care at feldsher and midwife centers]. PMID- 2879748 TI - [The localization and release of immunoreactive vasoactive intestinal polypeptide (VIP) in the bovine adrenal medulla]. AB - Vasoactive intestinal polypeptide (VIP), originally isolated from the porcine small intestine, is known to be widely distributed throughout the body including the central and peripheral nervous systems in various species. In the present study, we demonstrated the existence, subcellular distribution and mode of release of VIP-like immunoreactivity (VIP-LI) in the bovine adrenal medulla by radioimmunoassay. In tissue extracts from fresh bovine adrenal medulla, a considerable amount of VIP-LI (101.1 +/- 24.3 ng/g wet weight) was detected, and its concentration was about 100 times and 30 times higher than those of neurotensin-LI and somatostatin-LI, respectively, on a molar basis. On chromatographic analysis, the majority of adrenal VIP-LI was comfirmed to have the same molecular size as synthetic VIP, and a small peak of macromolecular VIP LI corresponding to pro-VIP was also found. In studies using a retrograde venous perfusion system of the bovine adrenal gland, marked releases of both VIP-LI and catecholamine (CA) were observed immediately after the infusion of potassium solution of a concentration of 56 mM in a Ca2+-dependent manner. Ba2+ (2 mM) also stimulated the releases of VIP-LI and CA from the adrenal gland Carbachol (10( 4)M) stimulated CA secretion as much as high potassium and Ba2+, but the magnitude of VIP-LI release was lower. The subcellular distribution of VIP in the adrenal medulla was investigated by a method of differential centrifugation and discontinuous density gradient. VIP-LI was mainly found in mitochondrial fraction, which contain mitochondria and synaptosome, while little was found in highly purified chromaffine granule fraction. These results suggest that VIP in the adrenal gland is mainly localized in the splanchnic nerve endings and may play a role as neurotransmitter/neuromodulator in the adrenal medulla. PMID- 2879749 TI - [Effect of prostaglandins on collagen synthesis in rabbit ovarian follicles during the ovulatory process]. AB - Collagen fibers in the ovarian follicle undergo drastic changes at ovulation due to the preovulatory increase of collagenolytic activities. The collagen synthesis in ovaries, however, has not been elucidated yet. To clarify the regulatory role of prostaglandins (PGs) in collagen synthesis of the follicular wall in relation to the ovulatory process, we measured prolyl hydroxylase (PH), as well as lysyl oxidase (LO) activity and the content of hydroxyproline (Hyp) in ovarian follicles of the rabbits treated by hCG, hCG/indomethacin (IM) and hCG/IM/various PGs. The experimental groups consisted of; 1) untreat control group 2) ovulatory group receiving hCG 3) non-ovulatory group given PGs 4) ovulatory group given hCG and PGs 5) group in which hCG-induced ovulation was inhibited by IM (4 mg/kg) 6) group in which IM-inhibited ovulation was recovered by PGF2 alpha (1.5 mg/kg) 7) group in which IM-inhibited ovulation was not restored by PGE1 (0.1 mg/kg) and PGE2 (0.7 mg/kg). The peak activities of PH and LO in ovarian follicles were observed at 12-13 hr after hCG injection, namely, immediately after ovulation. Significant changes of these activities after hCG administration were specific to the ovaries. PH activity in the ovaries was suppressed by the administration of IM, but LO activity was not significantly suppressed. In the hCG/IM/PGF2 alpha treated ovulatory rabbits (Group 6), PH activity recovered to nearly the level of the hCG-treated rabbits (Group 2). By addition of PGE2, ovulation did not recover but PH activity was restored to about 70% of the hCG-treated rabbits. PGE1 did not have any effect on the reversal of ovulation-blockage or restoration of PH activity. The amount of Hyp after hCG administration tended to decrease from 6 hr to 10 hr but was significantly increased from 10 hr to 13 hr. This increase of Hyp after ovulation significantly correlated with the increase of PH and LO activities. In the hCG/IM/PGF2 alpha-treated rabbits (Group 6), the changes of Hyp were similar to those the hCG-treated rabbits (Group 2). In conclusion, collagen synthetic activity, found to be regulated by PH and LO activities in the ovarian follicles, was activated after follicle rupture, resulting in reconstruction of collagen fibers, and PGs play an important role in the ovulatory process by modifying collagen synthesis. PMID- 2879750 TI - [The joining of dental solder. Gold is still the sustaining element]. PMID- 2879751 TI - Drugs in dentistry. Antihistamines. PMID- 2879752 TI - Antianxiety properties of lormetazepam. A double-blind crossover trial versus diazepam. AB - A double-blind crossover trial was carried out to compare the anxiolytic activity of lormetazepam vs diazepam. After 1 week of placebo, the drugs were administered for 4 weeks (10 drops twice daily) to 10 subjects with anxiety disorders. Each patient received either lormetazepam or diazepam and modifications of symptoms were evaluated through a series of tests at various intervals (days 0, 8, 16, 24, 32 and 40 of the study). Both drugs proved to be effective and significantly superior to placebo. They were both well tolerated. PMID- 2879753 TI - Effects of dopamine and somatostatin on phorbol ester-stimulated prolactin and growth hormone secretion. AB - Incubation of cultured ovine pituitary cells with the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) (0.1-100 nM), caused a dose related stimulation of both growth hormone (ED50 approximately 4 nM) and prolactin (ED50 approximately 14 nM) secretion. Stimulation by TPA (100 nM) produced a substantial 10-fold increase in growth hormone with a smaller, 2-fold rise in prolactin secretion over 30 min; significant effects on the release of both hormones occurred within 2 min. Treatment with TPA also produced a small, time- and concentration-dependent rise in cellular cyclic AMP content which reached, at maximum, a level 20-30% over basal values. Non-tumor-promoting phorbol esters did not stimulate the secretion of either growth hormone or prolactin. In the presence of TPA (10 nM), dopamine (1-1000 nM) suppressed prolactin secretion to a level close to that observed for maximal inhibition of unstimulated cells. At high concentrations (0.1-1.0 microM) dopamine also partially attenuated (by 43%) the TPA-induced stimulation of growth hormone secretion. Somatostatin (0.01-1.0 microM) completely inhibited the substantial (approximately 9-fold) TPA-induced stimulation of growth hormone secretion (inhibitory ED50 approximately 47 nM), and also suppressed TPA-stimulated prolactin secretion to the control level. Our results suggest that activation of protein kinase-C may be involved in the stimulatory regulation of both growth hormone and prolactin secretion in sheep pituitary cells. Failure of TPA to attenuate the inhibitory activity of dopamine and somatostatin suggests that inhibitory regulation occurs at, or beyond, the point in the secretory process regulated by protein kinase-C. PMID- 2879754 TI - The use of a tyrosine-hydroxylase cDNA probe to study the neurotransmitter plasticity of rat sympathetic neurons in culture. AB - We have compared quantitatively the effects of muscle-conditioned medium (CM) and elevated K+ concentration (40 mM) on the enzymatic activity of tyrosine hydroxylase (TH) and on TH-mRNA levels in primary cultures of rat sympathetic neurons. Northern blot analysis of RNA from cultured neurons with a 32P-labeled rat TH-cDNA probe was performed. The probe hybridized strongly with a single RNA species of 1.9 kb, similar in size to the TH-mRNA from PC12 pheochromocytoma cells. In agreement with earlier data both CM and a partially purified factor from CM increased choline acetyltransferase activity up to 200-fold and depressed TH activity by 2- to 7-fold in cultured sympathetic neurons. These effects were accompanied by a decrease in TH-mRNA level, which correlated with the decrease in TH activity. On the other hand, a culture medium supplemented with 40 mM KCl caused a 1.5- to 5-fold increase in TH activity, which was accompanied by an increase in TH-mRNA level of the same order of magnitude. As a working hypothesis, we suggest that CM and neuronal depolarization control the transcription of the TH gene in an antagonistic manner. PMID- 2879755 TI - Restriction-fragment-length polymorphisms of 5'-flanking region of insulin I gene in BB and other rat strains. Absence of association with IDDM. AB - Because the 5'-flanking hypervariable region of the human insulin gene may be associated with insulin-dependent diabetes mellitus (IDDM), we examined the spontaneously diabetic BB rat and other rat strains for polymorphisms of the two rat insulin genes, the localization of such polymorphisms, and their possible association with IDDM. By use of restriction-fragment-length polymorphism analysis, we found that the transcribed portion of the insulin I gene, its 3' flanking region, and the insulin II gene were not polymorphic. However, four alleles of the insulin I gene were identified, two of which (IA and IB) were found in BB rats. Alleles IA and IB varied in their 5'-flanking regions, yet neither was associated with IDDM in the BB rat. PMID- 2879756 TI - Hormone release from pancreatic islets perfused from venous side. AB - Directional blood flow in pancreatic islets may be important for regulation of islet hormone release. We therefore perfused an isolated canine pancreas via the celiac artery (arterial perfusion) and then via the portal vein (venous perfusion) in the same pancreas. Basal insulin and glucagon levels and their rate of release in response to 10 mM arginine, 11 mM glucose, 500 pg/ml somatostatin, or 500 pg/ml glucagon were similar under both conditions. However, the inhibition of glucagon release due to somatostatin and its recovery after the cessation of somatostatin infusion was poor in the case of venous perfusion. The basal somatostatin level and its release in response to 10 mM arginine, 11 mM glucose, and 500 pg/ml glucagon during venous perfusion was significantly higher than that during arterial perfusion. From these results, it is speculated that the directional blood flow in pancreatic islets may not be essential for regulation of hormone release from the canine pancreas or that such directionality does not exist in canine pancreatic islets, and that a considerable portion of released somatostatin may be taken up by the pancreas located downstream--probably in the exocrine pancreas. PMID- 2879757 TI - Role of hyperglucagonemia in maintenance of increased rates of hepatic glucose output in type II diabetics. AB - Elevated rates of basal hepatic glucose output (bHGO) are significantly correlated with the fasting serum glucose (FSG) level in subjects with non insulin-dependent diabetes mellitus (NIDDM). This observation suggests that bHGO is a major determinant of the severity of the diabetic state in these subjects. In addition, basal glucagon levels (bGL) are higher in these diabetics than in control subjects, despite the concurrent basal hyperglycemia and hyperinsulinemia, two factors known to suppress glucagon secretion. Although bGL is responsible for sustaining two-thirds of bHGO in normal humans, its role in sustaining elevated rates of bHGO in NIDDM has not been previously defined. To this end, we have studied 13 normal and 10 NIDDM subjects; mean FSG levels were 90 +/- 2 and 262 +/- 21 mg/dl, respectively (P less than .001). The mean fasting serum insulin and glucagon levels were higher in the diabetics than in the controls: 17 +/- 2 vs. 9 +/- 1 microU/ml (P less than .01) and 208 +/- 37 vs. 104 +/- 15 pg/ml (P less than .01), respectively. On separate days, HGO was assessed isotopically (with 3-[3H]glucose) in the basal state and during infusion of somatostatin (SRIF) (600 micrograms/h) alone and in conjunction with replacement infusions of glucose and insulin. The results demonstrate that bHGO is higher in diabetics than in controls (145 +/- 12 vs. 89 +/- 3 mg X m-2 X min-1, P less than .01); during infusion of SRIF alone, HGO was suppressed by 25% (P less than .05) and 34% (P less than .05) of the basal value in controls and diabetics, respectively; when the studies were repeated with glucose levels held constant at or near the FSG level by the glucose-clamp technique, the pattern and degree of HGO suppression was similar to that obtained by infusion of SRIF alone; during isolated glucagon deficiency (SRIF + insulin, 5 mU X m-2 min-1, with serum glucose maintained at basal level), HGO was suppressed by 71 +/- 8% of the basal value in controls (P less than .001) and by 58 +/- 7% in diabetics (P less than .001); and when isolated glucagon deficiency with similar hyperglycemia was created in control subjects, HGO was suppressed by 87% of the basal value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879759 TI - Mechanical properties and soldering of some cobalt base metal alloys. PMID- 2879758 TI - Similar dose responsiveness of hepatic glycogenolysis and gluconeogenesis to glucagon in vivo. AB - This study was undertaken to determine whether the dose-dependent effect of glucagon on gluconeogenesis parallels its effect on hepatic glycogenolysis in conscious overnight-fasted dogs. Endogenous insulin and glucagon secretion were inhibited by somatostatin (0.8 micrograms X kg-1 X min-1), and intraportal replacement infusions of insulin (213 +/- 28 microU X kg-1 X min-1) and glucagon (0.65 ng X kg-1 X min-1) were given to maintain basal hormone concentrations for 2 h (12 +/- 2 microU/ml and 108 +/- 23 pg/ml, respectively). The glucagon infusion was then increased 2-, 4-, 8-, or 12-fold for 3 h, whereas the rate of insulin infusion was left unchanged. Glucose production (GP) was determined with 3-[3H]glucose, and gluconeogenesis (GNG) was assessed with tracer (U-[14C]alanine conversion to [14C]glucose) and arteriovenous difference (hepatic fractional extraction of alanine, FEA) techniques. Increases in plasma glucagon of 53 +/- 8, 199 +/- 48, 402 +/- 28, and 697 +/- 149 pg/ml resulted in initial (15-30 min) increases in GP of 1.1 +/- 0.4 (N = 4), 4.9 +/- 0.5 (N = 4), 6.5 +/- 0.6 (N = 6), and 7.7 +/- 1.4 (N = 4) mg X kg-1 X min-1, respectively; increases in GNG (approximately 3 h) of 48 +/- 19, 151 +/- 50, 161 +/- 25, and 157 +/- 7%, respectively; and increases in FEA (3 h) of 0.14 +/- 0.07, 0.37 +/- 0.05, 0.42 +/ 0.04, and 0.40 +/- 0.17, respectively. In conclusion, GNG and glycogenolysis were similarly sensitive to stimulation by glucagon in vivo, and the dose response curves were markedly parallel. PMID- 2879760 TI - Soldering of dental alloys under vacuum by IR-heating. PMID- 2879761 TI - [The prospects for using endogenous modulators of functions and processes]. PMID- 2879762 TI - [Variability of the heart rhythm during mental work of varying intensity]. PMID- 2879763 TI - [Histologic aspect of the human gastric mucosa: relation to gastrin and somatostatin cells and the intraluminal secretion of these peptides]. AB - Fifty-eight subjects including controls, patients with duodenal ulcer, non operated or treated with a superselective vagotomy underwent endoscopic fundic and antral biopsies. Histologic classification of the two mucosae was performed. We examined the relationship between the histologic grade of gastritis in the two mucosae, then between the histologic aspect of the antral mucosa and antral gastrin-and somatostatin-cell densities, the basal intraluminal secretion of gastrin and somatostatin. There was a significant correlation between the histologic aspect of fundic or antral mucosa and the age of patients, except in the case of vagotomized patients. Fundic and antral histologic patterns were also correlated in each patient, except for vagotomized. Gastrin and somatostatin cell densities showed no variation in function of the degree of inflammation of non atrophic gastritis. These cell densities showed a tendency to decrease in atrophic gastritis, especially when intestinal metaplasia was present. Intraluminal gastrin secretion was increased in patients with mild atrophic gastritis (p less than 0.05 to p less than 0.02) in comparison with those whose histology was roughly normal. It was also increased in severe atrophic gastritis. The highest intraluminal secretion of somatostatin was observed in patients with mild atrophic gastritis while this secretion fell noticeably in those showing severe atrophic gastritis, as compared to the other groups. This work seems to suggest a relationship between intraluminal peptides and the evolution of gastritis. While results are still preliminary, they do not indicate that these peptides, thus released, play any pathophysiologic role. PMID- 2879764 TI - [Effect of nonselective beta-adrenergic actions on rat megakaryocytes and thrombocytes]. PMID- 2879765 TI - Cardiovascular effects of urotensin II in anesthetized and pithed rats. AB - Gillichthys urotensin II (GUII; 1.5-150 nmol kg-1) reduced blood pressure in anesthetized rats, diastolic pressure being reduced to a greater extent than systolic. The effect was slow in onset (peak at 4-5 min) and longlasting (up to 60 min), and was accompanied by a reflex tachycardia. The hypotension was not blocked by propranolol or by mepyramine. In pithed rats, GUII (150 nmol kg-1) reduced the pressor responses to sympathetic nerve stimulation, noradrenaline, and Arg-vasopressin. Somatostatin (150 nmol kg-1) had no effect on the sympathetic pressor response but reduced heart rate. It is concluded that GUII is a vasodilator in the rat, an action not shared with somatostatin. PMID- 2879766 TI - Somatostatin-28(1-14) immunoneutralization stimulates growth hormone secretion in fowl. AB - Immunoneutralization of endogenous somatostatin (SRIF)-28(1-14) by the intravenous or intramuscular administration of a specific antiserum promptly enhanced the growth hormone (GH) concentration in the plasma of 4 to 8-week-old cockerels. The magnitude of the GH response was related to the volume of antiserum administered. The release of GH from chicken pituitary glands incubated with intact hypothalami was increased in the presence of anti-SRIF-28(1-14). These results suggest that SRIF-28(1-14)-like peptides are physiologically involved in the control of GH secretion in chickens, in which they may tonically inhibit GH release. PMID- 2879767 TI - Somatostatin and altered medium osmotic pressure elicit rapid changes in prolactin release from the rostral pars distalis of the tilapia, Oreochromis mossambicus, in vitro. AB - Prolactin (PRL) cells in the rostral pars distalis of the tilapia Oreochromis mossambicus respond to somatostatin (SRIF) and reduced medium osmotic pressure within 10-20 min of exposure during perifusion incubation. Pieces of rostral pars distalis tissue were removed from freshwater-adapted tilapia and were preincubated in [3H]leucine in static culture (355 m phi smolal) for 48 hr. Following preincubation, they were placed in the perifusion apparatus and baseline release was established for 3 hr in hyperosmotic medium (355 m phi smolal). Exposure to hyposmotic medium (280 m phi smolal) resulted in a rapid and steep rise in the release of [3H]PRL, which remained elevated for more than 2 hr. When SRIF was added simultaneously with hyposmotic medium, the rise in PRL release normally initiated by reduced osmotic pressure was prevented. Somatostatin also quickly reduced release that had been previously elevated by exposure to hyposmotic medium. The time course of these changes suggests that SRIF and altered osmotic pressure act on PRL secretion in at least partial independence of effects which they may have on PRL synthesis in the tilapia pituitary. PMID- 2879768 TI - Studies on the regulation of growth hormone release from the proximal pars distalis of male tilapia, Oreochromis mossambicus, in vitro. AB - The in vitro effects of several factors, including cortisol, somatostatin (SRIF), and medium osmotic pressure, on growth hormone (GH) release from the tilapia pituitary were examined in relation to fish size. Spontaneous GH release from the proximal pars distalis (PPD) of approximately 60-g fish was significantly less than that from tissue of fish weighing either approximately 120 or approximately 280 g when incubated in 340 m phi smolal medium. While GH content of the PPD cultures (tissue + medium measured by densitometry) increased consistently with fish size, GH concentration (per microgram of tissue protein) was variable, being highest in 120-g fish and lowest in 280-g fish. Moreover, GH concentration was not related to GH release. Fish size also appeared to be important in the responsiveness of GH cells to stimulation by cortisol (Nishioka et al., 1985) and by increased osmotic pressure. In cultures of PPD from approximately 60-g fish, in which spontaneous release was relatively low, cortisol and increased medium osmotic pressure significantly enhanced release. Cortisol and hyperosmotic medium were without significant effect, however, on GH release from PPD of approximately 120-g fish, which showed high spontaneous release. In contrast, SRIF, a potent inhibitor of GH secretion, was effective in lowering GH release regardless of fish size. Nevertheless, SRIF was apparently more effective in inhibiting GH release from tissue of 60-g fish than from tissue of 120-g fish. Our data suggest that GH secretion may be augmented when smaller tilapia (approximately 60 g) are transferred to seawater, a situation in which blood cortisol and osmotic pressure would presumably be elevated. PMID- 2879769 TI - Prevalence and associations of apolipoprotein A-I linked DNA polymorphisms: results from a population study. AB - Subjects from a geographically defined population were screened for restriction fragment length polymorphisms linked to the apolipoprotein A-I (apoaA-I) gene locus. The polymorphic DNA fragments detected with an apoA-I cDNA probe after digestion with the restriction endonucleases Sac I (S1 and S2 alleles), Msp I (M1 and M2 alleles), or Pst I (P1 and P2 alleles) were used to define polymorphic haplotypes. The uncommon S2M1 haplotype was present in the leukocyte genomic DNAs of 6 of 22 (27%) subjects with high-density lipoprotein cholesterol (HDL-C) levels in the lowest decile, in contrast to none of the 20 subjects with HDL-C levels in the highest decile. With repeat determinations of the HDL-C levels 10 years later, the levels of the subjects in the low decile group with the S1M1 haplotype had regressed toward the population mean, while the regression was much less substantial for the S2M1 group. The mean triglyceride (TG) level in low HDL C subjects with the S2M1 haplotype was also higher than in those without it (295 vs 246 mg/dl), although not all of those with the S2M1 pattern were hypertriglyceridemic. The prevalence of the P2 allele was increased in a series of men with angiographically confirmed premature coronary artery disease (CAD) (P2 present in 7 of 43) as compared to a group of age-matched controls without CAD (1 of 36). There was no difference between these groups in the prevalence of the S2 allele. These results suggest that a particular pattern of apoA-I linked genetic polymorphisms is associated with lower HDL-C levels. This type of analysis will be useful in studies of the epidemiology of abnormal lipid states and may eventually provide a genetic marker to identify those at risk can be effectively instituted. PMID- 2879771 TI - Molecular cloning of nit-2, a regulatory gene required for nitrogen metabolite repression in Neurospora crassa. AB - We used an efficient sib-selection procedure to isolate a cosmid clone that complemented a mutated nit-2 gene of Neurospora crassa. Restriction fragment length polymorphism mapping indicated that the cosmid DNA insert was derived from linkage group IL, between 5S rDNA locus 12 and mt, the region of the N. crassa genome that contains nit-2. We conclude that the cosmid carries the nit-2 gene. PMID- 2879770 TI - Possible derivation of the laboratory mouse genome from multiple wild Mus species. AB - Laboratory strains of mice are thought to be derived from wild populations of Mus domesticus. Many instances of non-domesticus genetic information fixed in these strains have been described, however, and the amount of strain-to-strain genetic variation exceeds that found in wild domesticus populations. In order to estimate the extent of the non-domesticus contribution to laboratory mouse genomes, and to determine whether it could account for observed variation, we have used computer simulations to investigate the properties of genetically marked chromosomal segments and the distribution of residual allogenicity at various times during inbreeding. A locus or chromosomal segment is allogenic if it is unfixed within a lineage at a given time. The odds of fixation of a foreign chromosome segment are predicted to be an exponentially decreasing function of its length. The median segment length is predicted to be 17 centimorgans. Available data for markers of chromosomes 1, 9 and 12 in recombinant inbred strain sets conform to these predictions. Together, the results suggest that introgression of non-domesticus chromosomes and segregation of residual allogenicity are sufficient to account for the genetic diversity observed among inbred mouse strains and substrains. PMID- 2879772 TI - Sequence of glutamine synthetase from Salmonella typhimurium and implications for the protein structure. AB - To aid in the interpretation of the 3.5 A resolution electron density map of glutamine synthetase (GS) from Salmonella typhimurium, the nucleotide sequence of the gene coding for this enzyme has been determined. The predicted sequence of 468 amino acids (Mr = 51,628) has been compared to the sequence and sequence fragments reported by others for GS of Anabaena and Escherichia coli. The homology between the pairs of sequences is sufficiently strong to suggest that the overall three-dimensional structures of the three GS are similar. The predicted positions of alpha helices are in moderately good agreement with the electron-density map. PMID- 2879773 TI - Managing hypertension in chronic renal disease. AB - Hypertension is very common in the elderly patient with renal insufficiency and may be primary or secondary to the kidney disease. In these patients, hypertension is usually associated with an increase in peripheral vascular resistance and salt sensitivity (the latter related to the degree of renal failure.) Therapy should be tailored to the individual patient, particularly when the elevated blood pressure and renal insufficiency are associated with other significant medical problems. Most of the drugs used in younger hypertensives may be used in the elderly patient with renal insufficiency, but in general, starting and maintenance doses should be lower because of the greater sensitivity due to age and/or the renal failure. The goal in the elderly hypertensive patient with renal failure is similar to that in other hypertensive patients: blood pressure should be brought to 140/90 mm Hg or lower. In the elderly patient with resistant hypertension or who manifests a decrease in kidney function as blood pressure is lowered, an effort must be made to look for associated renovascular disease. PMID- 2879775 TI - [The June (1986) Plenum of the USSR Central Committee and the objectives of public health science in the RSFSR]. PMID- 2879774 TI - Interactions of oral antibiotics and common chronic medications. AB - Geriatric patients often require precise dose titration of certain drugs for effective, non-toxic treatment of chronic disease. When short-term antibiotic therapy is required, an oral antibiotic that would minimally disrupt a finely tuned chronic drug regimen would be most appropriate. Chronic medication antibiotic interactions are potentially more common with the use of erythromycin, tetracyclines, and sulfonamides. Clinicians should use care, and monitor for drug interactions when these agents are combined with chronically used drugs such as theophylline, warfarin, or carbamazepine. PMID- 2879777 TI - [Beta-adrenergic blockers and depression]. PMID- 2879776 TI - Effects of somatocrinin and a somatostatin antiserum on body and organ growth in the rat. AB - Chronic treatment with rGRF for 14 days with or without a specific antibody against somatostatin-14 were performed on 24-day old male Sprague-Dawley rats. Serum GH concentrations were significantly increased at the time of sacrifice while growth was not affected. rGRF, possibly through its effect on GH release, stimulated lung and kidney weights, increasing water content of the latter. Muscle and testes remained insensitive to GRF while the heart showed signs of reduced growth. Liver growth responded positively to the combined rGRF and ASS treatments whereas the pancreas exhibited loss of weight; on both of these organs, GH may act directly. The increased weights of gastric fundus and duodenum may result from an indirect action of GH on serum levels of gastrointestinal hormones such as gastrin. The results of this study stress the specific response of each organ to increased GH serum levels and indicate that their respective growth control factors cannot be generalized. PMID- 2879778 TI - [Interaction between digoxin, beta-blockers, calcium antagonists, and other cardiac drugs]. PMID- 2879779 TI - [Cryptorchidism in monozygotic twins]. PMID- 2879780 TI - Common forefoot problems in runners. AB - Forefoot injuries constitute a significant portion of the problems that affect runners. With the increasing popularity of recreational running, more emphasis on the treatment of specific running injuries has surfaced. For the orthopaedic surgeon interested in treating runners, a thorough understanding of foot anatomy, biomechanics, shoes, orthotics, running surfaces, and conservative and surgical treatment options is mandatory. Runners place high demands on their feet and therefore require careful evaluation prior to embarking on a specific treatment course. This article represents a current overview of common problems affecting the forefoot of recreational and world-class runners. Treatment plans are based on the senior author's experience in the care of runners over the past 14 years. PMID- 2879781 TI - [Hypertension and heart failure--treatment with enalapril. Results of international studies on clinical applications]. PMID- 2879782 TI - Nocturnal acid suppression with a new H2 receptor antagonist--nizatidine. AB - To determine the potential efficacy of bedtime doses of the new furan H2 receptor antagonist nizatidine in the suppression of nocturnal acid secretion, this randomized, crossover, single-blind study was performed in 10 healthy male subjects. The actions of a single bedtime (21:00 hour) dose of the H2 receptor antagonists nizatidine (150 mg and 300 mg), ranitidine (300 mg) and cimetidine (800 mg), as well as placebo on nocturnal gastric acid and volume secretion (01:00 to 07:00 hours, and on overall 24 hour H+ ion concentration were studied. Compared with placebo, night-time (23:00 to 07:00 hours) H+ ion concentration was reduced by 70, 79, 95, and 76% (p less than 0.05-p less than 0.01). Nocturnal acid secretion, too, was significantly lower for the H2 blockers than for placebo (p less than 0.05-p less than 0.01). A significant reduction in night-time gastric volume secretion was observed in the hourly intervals from 04:00 to 07:00 hours and in total volume in the whole 6 hours period (p less than 0.05-p less than 0.01). Nizatidine 300 mg nocte, ranitidine and cimetidine significantly decreased H+ concentration for only 1 hour (08:00 to 09:00 hours, p less than 0.05-p less than 0.01) during the subsequent daytime period (08:00 to 13:00 hours). Since no significant pharmacodynamic differences between nizatidine 300 mg nocte, cimetidine 800 mg nocte and ranitidine 300 mg nocte were observed, it may be concluded that at the doses employed, these three H2-blockers will all be similarly effective in the acute therapy of peptic ulcer disease. PMID- 2879783 TI - Luminal leakage of HCO3 in chronic antral erosions. AB - Gastric bicarbonate content has been determined, under basal conditions, in ten patients with chronic antral erosions, and in ten healthy controls. The former group showed a significantly higher (p less than 0.01) than normal luminal concentration of HCO3. After medical treatment gastric bicarbonate content returned to normal in patients showing endoscopic healing, but not in subjects with persisting erosions. It is suggested that in chronic antral erosions, extensive disruption of mucosal integrity leads to passive leakage of bicarbonate into the gastric lumen. PMID- 2879784 TI - Biosynthesis of pancreatic islet hormones. AB - We have outlined the various strategies used to characterize the precursors of three pancreatic islet hormones--somatostatin, pancreatic polypeptide and VIP. In each case, isolation of the cDNA clones was facilitated by the use of gastrointestinal tissues that were extremely rich in specific mRNA. Characterization of the structures of the precursors is clearly only the first step in understanding the regulation of pancreatic hormone biosynthesis. It is likely that the availability of the cDNA clones will allow us to define the actual mechanisms underlying hormone production within the pancreas. PMID- 2879785 TI - Lithium in schizophrenia. PMID- 2879786 TI - Association between type of medication instruction and patients' knowledge, side effects, and compliance. AB - The authors measured knowledge about medication and its side effects, impact of side effects, and compliance in 30 chronic outpatients before and after they participated in two instruction sessions about their medication held one month apart. Instruction consisted of a verbal or a written and verbal presentation and minimum or maximum information about side effects. All patients' medication knowledge increased after both sessions. Those on high doses of neuroleptics given verbal and written information gained significantly more medication knowledge than those given only verbal information. After instruction, more patients knew about specific side effects, including tardive dyskinesia, and both patients given only verbal instruction and those given minimum information about side effects had fewer problems with side effects. Instruction did not affect compliance. PMID- 2879787 TI - Overcoming institutional and community resistance to a tardive dyskinesia management program. AB - A growing body of research has examined psychiatry's previously hesitant response to the problem of tardive dyskinesia, but little has been said about resistance among institutions and communities to managing tardive dyskinesia. This paper describes how staff of a tardive dyskinesia management program overcame such resistance in both an inpatient and an outpatient setting and implemented tardive dyskinesia guidelines promulgated by an American Psychiatric Association task force in 1979. Through educational and liaison activities, the program staff overcame the fears of nurses and community sponsors of outpatients about reducing or withdrawing patients' neuroleptic medication. Implementation of the program required strong support from the hospital administration and an increase in communication between the various services and outpatient programs treating patients with tardive dyskinesia. PMID- 2879788 TI - Association of a DNA polymorphism in the apolipoprotein C-III gene with diverse hyperlipidaemic phenotypes. AB - We found an increased prevalence of an Sst-1 restriction fragment length polymorphism (RFLP), localized to the apolipoprotein C-III gene, in lipid clinic patients with diverse hyperlipidaemic phenotypes. Studies on a normolipidaemic control population confirmed previous reports of differing frequencies of the RFLP in different racial groups. Reexamination of the patient data, taking into account racial composition, provided further support for an association of the Sst-1 RFLP with primary hypercholesterolaemia, type III hyperlipoproteinaemia, as well as with hypertriglyceridaemia as had previously been observed. These results suggest that the Sst-1 site is linked to a gene defect with a minor or subtle phenotypic effect which enhances the expression of a co-existent major monogenic defect of lipoprotein transport. PMID- 2879789 TI - Functional and molecular studies of V genes expressed in autoantibodies. PMID- 2879790 TI - Left ventricular hypertrophy in hypertension. Prevalence and relationship to pathophysiologic variables. AB - In less than a decade since development of echocardiographic measurement of left ventricular muscle mass, studies using this technique have provided considerable information about the prevalence and pathophysiology of left ventricular hypertrophy in human hypertension. Increased left ventricular mass has been found in a significant minority of patients with systemic hypertension, with the exact prevalence dependent both on how a population is selected and on the sex, race, and possibly age composition of its members. All published studies have reported that left ventricular hypertrophy is more closely related to blood pressure recorded in the patient's natural setting during normal activity or exercise whether measured by portable recorder or home manometer-than to blood pressure measured by the physician. In addition, studies indicate that the classic hypertensive abnormalities of concentric left ventricular hypertrophy and increased peripheral resistance are interrelated, while left ventricular hypertrophy is absent in a subgroup of patients with mild essential hypertension who exhibit high cardiac output and evidence of supernormal myocardial contractility. Conversely, the left ventricular functional response to exercise is inversely related to the degree of hypertrophy. High levels of blood viscosity, which would tend to blunt the reduction in peripheral resistance expected during sleep or exercise, have also been associated with left ventricular hypertrophy in patients with essential hypertension. Echocardiographic studies have provided evidence both for and against the hypothesis that activity of the sympathetic or reninangiotensin systems plays a direct role in causing hypertensive cardiac hypertrophy. These findings demonstrate the useful role that echocardiographic assessment of left ventricular structure and function may play in hypertension research. PMID- 2879791 TI - Characterization of genes encoding type 1 fimbriae of Klebsiella pneumoniae, Salmonella typhimurium, and Serratia marcescens. AB - With a minicell system, the organization of genes encoding type 1 fimbriae of Salmonella typhimurium, Klebsiella pneumoniae, and Serratia marcescens was determined. In all cases multiple gene products were necessary for the phenotypic expression of fimbriae; thus fimbrial expression in these strains is similar to that in Escherichia coli. The type 1 fimbrial subunit gene was detected by the ability of its product to react with specific antiserum. At least six genes were found to be involved in the expression of type 1 fimbriae by S. typhimurium, and at least four genes constituted the fimbrial gene cluster of K. pneumoniae. In the case of S. marcescens, a minimum of three detectable polypeptides was required for the production of fimbriae. Also, a gene probe consisting in part of nucleotide sequences from the E. coli fimbrial subunit gene hybridized to a discrete DNA fragment derived from the plasmid encoding K. pneumoniae fimbriae. Such a fragment was assumed to contain a gene encoding the structural component of the type 1 fimbriae. Each of the three cloned systems encoded a number of polypeptides which varied in size; thus, the organization and molecular weight of fimbrial accessory proteins of each genus were not identical. PMID- 2879792 TI - Distribution of type 1 and P pili on uropathogenic Escherichia coli O6. AB - The distribution of type 1 and P pili on individual cells of an O6 uropathogenic Escherichia coli strain, 6260, was determined immunologically with pilus-specific monoclonal antibodies by indirect immunofluorescence and immunogold electron microscopy. Variations in pilus expression under different culture conditions were monitored with an indirect immunofluorescence assay; 63% of piliated cells expressed type 1 pili when grown on agar at 37 degrees C versus 14 to 38% when grown in broth at 37 degrees C. In contrast, generally fewer cells with P pili (18 to 44%) were detected on agar than when grown in broth (up to 86%). Both type 1 and P pili were absent from cells cultured at 20 degrees C. Immunogold and immunofluorescence double labeling techniques with monoclonal antibodies 11-2 and 91-1 were used to study subpopulations of cells with type 1 and P pili; 39 to 41% of the piliated cells demonstrated only type 1 pili, and 12 to 16% of the cells showed only P pili. The immunogold method proved more sensitive than the immunofluorescence technique for detecting subpopulations expressing both pili types simultaneously, 19 versus 7%. We observed variations between type 1 and P pili, both in expression on individual cells and in the distribution of subpopulations of cells. PMID- 2879793 TI - Malaria transmission-blocking immunity induced by natural infections of Plasmodium vivax in humans. AB - Immunity to malarial infections in human populations is known to affect the development of the asexual blood stages of the parasites in the human host and to be capable of conferring significant protection against morbidity and mortality due to the disease. In this study we show that during acute infection with Plasmodium vivax malaria, one of the two main malarial pathogens of humans, most individuals also develop immunity that suppresses the infectivity of the sexual stages of the parasite to mosquitoes. The immunity is antibody mediated and is directed against the parasites in the mosquito midgut shortly after ingestion of blood by a mosquito. This immunity could be expected to have significant effects on the natural transmission of P. vivax malaria. PMID- 2879794 TI - Relationship of type 1 pilus expression in Escherichia coli to ascending urinary tract infections in mice. AB - The role of type 1 pili and P adhesins during the in vivo growth of Escherichia coli inoculated into the urethras of BALB/c mice was studied. Strains which produced type 1 pili when grown in broth but lost this trait when grown on agar (regulated variants) were tested. Broth-grown organisms colonized the bladder of every animal tested, with counts of 10(3) to 10(4) viable organisms recovered from bladder homogenates. Agar-grown organisms gave lower rates of infection and the number of viable organisms recovered from bladders was significantly reduced. The degree of inoculum piliation influenced bladder colonization in a direct way: as piliation increased, the number of bacteria recovered from bladders also increased. After intraurethral inoculation, all of the bladders and 44% of the kidneys were colonized on day 1, and by day 5, 94% of the bladders and 16% of the kidneys were positive. Hemagglutination titers remained high for the bladder isolates, but the organisms colonizing the kidneys became significantly less piliated with time. Bacteriuria was unrelated to bladder or renal colonization. Strains that demonstrated random phase variation of type 1 pili during growth on agar produced similar colonizations of the urinary tract with broth- and agar grown inocula. Strains that produced only P adhesins were less effective in colonizing the urinary tract than were type 1 piliated organisms. Other strains which did not produce pili only minimally colonized the bladder. The results suggest that type 1 pili play an essential role in ascending infections of the urinary tract. PMID- 2879795 TI - Adherence to human colonocytes of an Escherichia coli strain isolated from severe infantile enteritis: molecular and ultrastructural studies of a fibrillar adhesin. AB - Escherichia coli 469-3 (O21:H-) was isolated from a child with severe enteritis. Ultrastructural analysis of the surface of the strain indicated the presence of very fine fimbriae which mediated mannose-resistant hemagglutination of human blood and caused the bacteria to adhere to human epithelial cell lines and to brush borders of isolated human colonic, but not duodenal, enterocytes. A cosmid library of total DNA of the strain, expressed in laboratory strains of E. coli, was screened by a rapid hemadsorption method, and a number of positive clones were identified. Restriction endonuclease fragments specifying mannose-resistant adherence were subcloned from the cosmid DNA of a strongly hemagglutinating clone in a plasmid vector. The identity of the adhesin was confirmed by biochemical, electron-microscopic, and immunological comparisons with the adhesin synthesized by the clinical isolate. It comprised a high-molecular-weight aggregate of a 14,000-dalton subunit protein which bound antiserum raised against the mannose resistant adhesin of strain 469-3. The adhesin was synthesized by both the clone and the parental strain at growth temperatures above 18 degrees C but by only a fraction of the cells in a pure culture, although all the bacteria which adhered to human cells expressed the protein. PMID- 2879797 TI - Mechanism of antianaphylactic action of beta-agonists in allergic inflammation of air pouch type in rats. AB - Using an experimental model of allergic inflammation of air pouch type in rats, the mechanism of antiallergic action of beta-agonists was examined. In this model an immediate increase in vascular permeability and histamine level in the pouch fluid was observed after injecting the antigen (azobenzene arsonate-conjugated acetyl bovine serum albumin) solution into the preformed air pouch on the back of the sensitized rats. The same type of reaction was inducible by injecting anti rat IgE into the preformed air pouch, but not IgG2a. This fact indicates that the immediate increase in vascular permeability and histamine level is an IgE mediated anaphylactic reaction. When beta-agonists such as isoproterenol, procaterol and salbutamol were injected into the air pouch together with the antigen, the anaphylactic increase in vascular permeability was suppressed dose dependently without concomitant decrease in histamine level in the pouch fluid. In contrast, disodium cromoglycate, an inhibitor of degranulation of mast cells, the anaphylactic vascular permeability increase was suppressed in parallel with a decrease of the histamine level. Propranolol, a beta-antagonist, counteracted the effect of beta-agonists. Serotonin-induced vascular permeability was also suppressed dose-dependently by treatment with beta-agonists. Furthermore, vascular permeability in the postanaphylactic phase of the present experimental model was also suppressed by isoproterenol. These results indicate that beta agonists exert their antiallergic effect by inhibiting the reactivity of local vasculature to chemical mediators released from mast cells. PMID- 2879796 TI - A plasmid of enterohemorrhagic Escherichia coli O157:H7 is required for expression of a new fimbrial antigen and for adhesion to epithelial cells. AB - Of 14 strains of Escherichia coli O157:H7 isolated from patients with hemorrhagic colitis or hemolytic uremic syndrome that were examined for fimbriae, the presence of plasmids, and the ability to adhere to intestinal cells, 13 possessed a 60-megadalton plasmid and were fimbriated as assessed by electron microscopy. These strains adhered to Henle 407 intestinal cells but not to HEp-2 cells or erythrocytes. Three strains were cured of the plasmid and thereafter failed to express fimbriae and lost the ability to adhere to intestinal cells. Conversely, E. coli K-12 transformed with the 60-megadalton plasmid from each of the three strains produced fimbriae and was able to adhere to intestinal cells. A single fimbrial subunit of 16 kilodaltons was observed when purified fimbriae from the transformants and from the 60-megadalton plasmid-containing E. coli O157:H7 strains were disaggregated and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antisera raised against one preparation of the purified fimbriae reacted strongly with 12 of 14 O157:H7 isolates in an agglutination assay and with purified fimbrial preparations from five E. coli O157:H7 strains in an enzyme-linked immunosorbent assay. PMID- 2879798 TI - Regulation of antibody-dependent cellular cytotoxicity in multiple sclerosis by central nervous system hormones. AB - Using oligodendrocytes from primary brain cultures as targets in an antibody dependent cellular cytotoxicity (ADCC) assay, we have examined the effects of insulin and histamine on killer cells in multiple sclerosis (MS) and other neurological disease (OND) controls compared to normal healthy controls. The effects were shown to be specific for effectors by preincubation experiments. MS patients' ADCC to primary oligodendrocytes was depressed, but could be boosted to normal control levels by histamine binding to the H1 receptor. Significant elevation of MS ADCC by cimetidine alone suggested that endogenous histamine production and H2 receptor binding could be mediating a suppressive effect on MS ADCC to oligodendrocytes. In addition, MS ADCC could be boosted significantly by insulin. MS killer cells were more sensitive in vitro to the boosting effects of both histamine and insulin than either OND or normal controls, both in dose response and magnitude of the increased ADCC. PMID- 2879799 TI - Changes in the volume and histology of retractile testes in prepubertal boys. AB - Testicular development was studied in prepubertal boys with retractile testes. Testicular volume, the diameter of the seminiferous tubules and the number of spermatogonia in the tubules were decreased in cases of unilateral retractile testis, when compared with values for the contralateral normally descended testis. On the other hand, in patients with a unilateral retractile testis and contralateral inguinal testis, there was no difference in the developmental parameters between the two testes. These results suggest that the retractile testis has developmental failures characteristic of a cryptorchid testis and therefore requires orchiopexy. PMID- 2879801 TI - Intratesticular factors and testosterone secretion: the effect of treatment with ethane dimethanesulphonate (EDS) and the induction of seminiferous tubule damage. AB - The role of seminiferous tubule dysfunction in regulating the levels of a factor (or factors) in testicular interstitial fluid (IF) which stimulates Leydig cell testosterone secretion in vitro, was assessed by injecting rats with the Leydig cell toxin, EDS. Within 72 h of treatment EDS destroyed the Leydig cells and concomitantly reduced IF testosterone to undetectable levels. This was associated with nearly a 2-fold increase (P less than 0.001) in levels of the IF-factor(s) as judged by the enhancement of hCG-stimulated testosterone production (= IF bioactivity). By 3 weeks, and thereafter up to 10 weeks post-EDS, Leydig cells regenerated within the testis, and testosterone levels returned to control values, but IF-bioactivity remained significantly increased. The latter was associated with seminiferous tubule dysfunction as indicated initially by testicular morphology, raised serum levels of FSH and reduced testicular weight. For animals with normal testosterone levels, there was a significant negative correlation (r = -0.57, N = 46; P less than 0.001) between testicular weight and IF bioactivity. A similar increase in IF bioactivity in the presence of normal testosterone levels was observed in rats in which patchy severe seminiferous tubule damage had been induced by short-term cryptorchidism. It is concluded that, in addition to testosterone, seminiferous tubule function may dictate the intratesticular levels of the testosterone-stimulating factor(s) in IF. PMID- 2879800 TI - Regulation of interstitial cell function by seminiferous tubules in intact and cryptorchid rats. AB - The effects of experimental cryptorchidism on seminiferous tubule secretions and interstitial cell testosterone production were studied in vitro. Spent media obtained from incubations of seminiferous tubules (SMST) from cryptorchid rats caused a significant increase in testosterone production when added to interstitial cells isolated from intact rats. The previously noticed inhibitory activity of the SMST from stages VIII-XI of the spermatogenic epithelial cycle gradually disappeared after the induction of experimental cryptorchidism. SMST obtained from both sham-operated or cryptorchid rats stimulated basal testosterone production when added to interstitial cells from cryptorchid rats. SMST from rats had been cryptorchid for 7, 14 and 28 days stimulated testosterone production when added to interstitial cells prepared from intact animals. Seminiferous tubules from cryptorchid rats therefore appear to be the source of a heat stable, trypsin-resistant factor with an apparent molecular weight of between 5000 and 10,000 daltons which stimulates testosterone production when added to interstitial cells in vitro. Its activity could not be blocked by an LRH antagonist. This factor enhances both basal and LH-stimulated secretion of testosterone in contrast to the inhibitory activity which involves only a partial blockade of LH-dependent steroidogenesis. PMID- 2879802 TI - Age and first experience with psychoactive drugs. AB - By utilizing the Gutman Scaling technique and by plotting acquisition curves, a number of different patterns of involvement with different psychoactive drugs were discerned. A stable, sequential, and cumulative hierarchy of experience with drugs was found to be established at age 15, but different peak years exist for trying different drugs. It was also found that drug use may be cumulative for some drugs and not for others. Special emphasis has been given to discussing the research implications that have arisen from the present study. PMID- 2879803 TI - Neuroendocrine effects of setoperone: a new neuroleptic drug. AB - Setoperone (R 52245), a serotonin S2 and dopamine D2 receptor blocker, was tested on eight healthy male volunteers, receiving 5 or 40 mg orally, in order to assess the modifications of plasma prolactin levels, as an index of receptor blocking activity. Both doses significantly increased plasma levels, confirming the dopamine blocking activity. In vitro and in vivo studies have shown serotonin S2 receptor blockade and lysergic acid diethylamide antagonist activity. Setoperone is proposed as a possible new neuroleptic drug. PMID- 2879805 TI - Failure of a combined anti-histamine and anti-leukotriene treatment to suppress passive anaphylaxis in the guinea-pig. AB - Ovalbumin was used to trigger passive systemic anaphylactic shock in guinea-pigs treated with serum provided by actively sensitized animals. Shock was characterized by bronchoconstriction and hypotension, accompanied by leukopenia and moderate thrombocytopenia. Neither aspirin, a cyclooxygenase inhibitor, FPL 55712, a peptido-leukotriene antagonist, nor their combination interfered with shock, under conditions where the selective histamine antagonist mepyramine, up to 20 micrograms/kg, suppressed bronchoconstriction. When the animals were treated with the beta-adrenergic antagonist propranolol, mepyramine lost its activity, even if combined with aspirin and FPL 55712. Lungs provided by the sensitized animals secreted histamine and formed thromboxane A2 when challenged with ovalbumin, but failed to do so when the lungs were collected after systemic shock; demonstrating that in vivo desensitization involves direct effects on the lungs. Parenchyma lung strips from the sensitized animals and lung strips and trachea from non-sensitized animals placed together in an organ bath contracted when exposed to the antigen in presence of mepyramine. The contraction of the sensitized strips was not affected by FPL 55712 nor by the lipoxygenase inhibitors nordihydroguarietic acid and BW755c, but the responses of the non sensitized tissues were suppressed, demonstrating that, apart from peptido leukotrienes, parenchyma lung strips from passively sensitized animals generate a leukotriene and histamine-independent contracting activity. Histamine and peptido leukotrienes do not account for the totality of passive anaphylactic shock in the guinea-pig. PMID- 2879806 TI - Lymphomatoid papulosis, cutaneous T-cell lymphoma, and Hodgkin's disease: diseases of activated helper T cells? PMID- 2879804 TI - The effect of cyclophosphamide in vivo on the expression of lymphocyte markers, detected by monoclonal antibodies, in the rat. AB - Surface markers on lymphocytes from the thymus, lymph node and spleen of the rat were examined in single cell suspensions using a panel of monoclonal antibodies. These were used particularly to investigate Pan T, TH (T-helper), TS/C (T suppressor-cytotoxic) and Ia antigens. The expression of these markers in rats treated with a single dose of cyclophosphamide (100 mg/kg body weight) was followed for 3 weeks after treatment. Maximum changes were detected at 3 days and recovery took up to 3 weeks to near completion. Comparison was made with histological observations of the effect of CY on these organs. At 3 days, the thymus showed maximum weight loss and gross cortical depletion. This associated with significant drop in the expression of the TS/C marker on small and large lymphocytes. Regeneration of the cortex, beginning at 7 days, was associated with the presence of many large pyroninophilic cells. This was accompanied by an increase in the expression of the TS/C marker on both small and large lymphocytes. The mesenteric lymph node showed marked depletion of the B-cell areas at 3 days. There was also a significant drop in TS/C and Ia expression and a marked rise in Pan T and TH. TS/C expression recovered rapidly with a rebound at 7 days. However, the expression of Pan T and TH did not return to normal until 21 days. In the spleen there was a similar decrease in the lymphocytes populating the B-cell areas at 3 and 7 days with an increase in the expression of Pan T and TH, and a decrease in the expression of Ia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879807 TI - Influence of amino acid, somatostatin and somatostatin-glucagon infusion on resting metabolic rate, assessed by indirect calorimetry, in normal non-obese subjects. PMID- 2879808 TI - Autoimmune diseases of the peripheral cornea. PMID- 2879809 TI - Biological aspects of depression: a review of the etiology and mechanisms of action and clinical assessment of antidepressants. PMID- 2879811 TI - [Regulation of the secretion of gastrointestinal peptide hormones]. PMID- 2879810 TI - [Is there a sensible use for somatostatin in gastroenterology?]. PMID- 2879812 TI - Beta-blockers and the patient with bronchial disease. PMID- 2879813 TI - Salivary and blood levels of neuroleptics during outpatient maintenance treatment. PMID- 2879814 TI - Beta-adrenergic blocking agents in congestive heart failure. PMID- 2879816 TI - Cardiovascular effects of tricyclic antidepressants. PMID- 2879815 TI - New polymorphisms of HLA-B27 and other B locus antigens detected by RFLP using a locus-specific probe. AB - Genomic DNA from 46 B27+ ankylosing spondylitis, Reiter's syndrome, or normal individuals was digested with Taq I and probed, in Southern blots, with the HLA-B locus specific probe, EI7. Four restriction fragment length polymorphisms (RFLP), 2.5, 3.4, 3.8 and 4.0 or 8.0 kb, were observed for the B27 gene. In Caucasians, one of the B27 variants (2.5 kb) was more frequent in normals and almost never appeared in patients, suggesting a trend that is not yet statistically significant. In the course of defining the B27 polymorphisms, three and two RFLP, respectively, were also found for the B18 and B44 genes. PMID- 2879817 TI - Predicting residency performance. PMID- 2879818 TI - In search of an exit. PMID- 2879819 TI - More on influenza A and pneumonitis. PMID- 2879820 TI - Coping with the stress of malpractice litigation. PMID- 2879821 TI - Intracoronary streptokinase and fatal cerebellar hemorrhage. PMID- 2879822 TI - A consideration in evaluation of short stature. Cohen syndrome. PMID- 2879823 TI - The viewbox. Computed tomography. PMID- 2879824 TI - Kynurenic acid and gamma-D-glutamylaminomethylsulfonic acid suppress the compound action potential of the auditory nerve. AB - Kynurenic acid and gamma-D-glutamylaminomethylsulfonic acid, two excitatory amino acid antagonists, were perfused through the guinea pig cochlea while monitoring various cochlear potentials. Both drugs (0.6-10 mM) reduced the magnitude of the compound action potential (CAP) of the cochlear nerve without much effect on other potentials. The results are consistent with the hypothesis that the hair cell transmitter is an excitatory amino acid, possibly L-glutamate. PMID- 2879825 TI - Effects of almitrine on genioglossal and diaphragmatic electromyograms. AB - We previously demonstrated dose-dependent increases in both hypoglossal and phrenic electroneurograms after almitrine in anesthetized, paralyzed, and vagotomized cats. We have now investigated the effect of this peripheral chemoreceptor stimulant on diaphragmatic and genioglossal (GG, an upper airway maintaining muscle) electromyograms in five unanesthetized, chronically instrumented, spontaneously breathing adult cats during slow-wave sleep. In 12 studies almitrine doses of 1.0-6.0 mg/kg increased inspired minute ventilation (VI), frequency (f), and tidal volume (VT) and decreased expiratory time (TE). However, almitrine doses as high as 6.0 mg/kg failed to augment phasic inspiratory GG activity. To determine why almitrine induced phasic inspiratory upper airway activity in anesthetized, vagotomized cats but not in sleeping cats, additional studies were performed. In four dose-response studies in three pentobarbital-anesthetized cats, almitrine, 1.0-6.0 mg/kg, did not produce phasic inspiratory GG activity. Almitrine did induce phasic inspiratory GG activity in two of three studies in three vagotomized, tracheostomized, alpha-chloralose urethan-anesthetized cats. These results suggest that almitrine would not be useful in obstructive sleep apnea, yet because almitrine markedly increased VI, f, and VT and decreased TE in unanesthetized sleeping cats the drug may be effective in patients who lack normal central neural respiratory drive, such as the preterm infant. PMID- 2879827 TI - Thin layer chromatographic identification of phenothiazine derivative drugs: interlaboratory study. AB - A thin layer chromatographic method for the identification of phenothiazine derivative drugs was studied collaboratively by 8 laboratories. Twenty phenothiazine drugs were examined by each collaborator. The identification scheme depends on the color of the sprayed spots and the Rf values relative to the Rf of chlorpromazine (RCHL) in 4 solvent systems. In 98.13% of the cases, a correct identification could be made; the remaining drugs were reduced to a choice between pairs of phenothiazines. With respect to chlorpromazine, the data showed a significant decrease in variability of RCHL values compared with Rf values in the 4 solvent systems. PMID- 2879826 TI - Synthesis of barbituric acid derivatives and their effect on survival of functional hepatocytes from adult rats in primary culture. AB - Ten barbituric acid (BA) derivatives were synthesized and tested for their potency for supporting survival of functional hepatocytes from adult rats in primary culture. Of the 10 BA derivatives, 7 compounds (C-2, 3, 4, 5, 6, 9, and 10) efficiently supported hepatocyte survival for at least 2 wks in primary culture. Especially C-5, 6, and 9 showed excellent efficiency for such action. The optimum concentrations of the BA derivatives for observing the morphological and biochemical effects differed from each other. The maintenance of hepatocytes was attained only in the continuous presence of the BA derivatives in the medium. The morphologic features of hepatocytes surviving in the presence of the BA derivatives resembled those of hepatocytes 24 h after inoculation. The surviving hepatocytes secreted remarkably large amounts of albumin into the culture media. Tyrosine aminotransferase (TAT) activity was higher in the 1-wk-old cultures treated with C-5, 6, and 9 than in the freshly isolated hepatocytes. The addition of dexamethasone (10 microM) caused a 1.7 to 2.1-fold induction in TAT activity. The basal levels of TAT activity and the induction rates increased in the cultures treated with C-5 and 6 from Week 1 to 2 of primary culture. PMID- 2879828 TI - Teichoic acid-containing muropeptides from Streptococcus pneumoniae as substrates for the pneumococcal autolysin. AB - Pneumococcal cell walls in which the normal phosphorylcholine component of the wall teichoic acids is replaced with phosphorylethanolamine cannot absorb the homologous autolytic enzyme and are completely resistant to autolytic degradation (S. Giudicelli and A. Tomasz, J. Bacteriol. 158:1188-1190, 1984). We have now isolated and characterized soluble teichoic acid-containing muropeptides from such cell walls and tested them as substrates for the pneumococcal autolytic enzyme. Both choline- and ethanolamine-containing muropeptides were hydrolyzed to the same extent by the enzyme. Furthermore, free choline concentrations that totally inhibited the digestion of pneumococcal cell walls in vivo and in vitro were without effect when the soluble substrates were used. PMID- 2879829 TI - Involvement of glutamate in the respiratory metabolism of Bradyrhizobium japonicum bacteroids. AB - Bradyrhizobium japonicum bacteroids were isolated anaerobically and supplied with 14C-labeled succinate, malate, aspartate, or glutamate for periods of up to 60 min in the presence of myoglobin to control the O2 concentration. Succinate and malate were absorbed about twice as rapidly as glutamate and aspartate. Conversion of substrate to CO2 was most rapid for malate, followed by succinate, glutamate, and aspartate. When CO2 production was expressed as a proportion of total carbon taken up, malate was still the most rapidly respired substrate, with 68% of the label absorbed converted to CO2. The comparable values for succinate, glutamate, and aspartate were 37, 50, and 38%, respectively. Considering the fate of labeled substrate not respired, greater than 95% of absorbed glutamate remained as glutamate in the bacteroids. In contrast, from 39 to 66% of the absorbed succinate, malate, or aspartate was converted to glutamate. An increase in the rate of CO2 formation from labeled substrates after 20 min appeared to coincide with a maximum accumulation of label in glutamate. The results indicate the presence of a substantial glutamate pool in bacteroids and the involvement of glutamate in the respiratory metabolism of bacteroids. PMID- 2879830 TI - Identification and characterization of genes determining receptor binding and pilus length of Escherichia coli type 1 pili. AB - We describe the identification and characterization of two genes and their gene products responsible for determining receptor binding and pilus length in type 1 piliated Escherichia coli. One gene, pilE, conferred the ability of piliated cells to agglutinate guinea pig erythrocytes. The other gene, pilF, determined pilus length, in that mutants having lesions in pilF had very long pili. The two genes were detected after Tn5 mutagenesis of a cloned segment of DNA that normally complemented a pilE lesion in the chromosome. Thus, lesions in pilE or pilF on the cloned segment resulted in mutants having the PilE- phenotype (piliated but unable to agglutinate erythrocytes). Introduction of the plasmid encoded mutant alleles of pilE and pilF into the chromosome followed by electron microscopic examination of the mutants showed that only lesions in pilF conferred the striking increase in pilus length. Mutations in pilF could be complemented in trans by the original cloned segment to produce cells with parental-length pili. Minicell transcription and translation of the cloned pilE and pilF genes having representative Tn5 insertion mutations showed that the pilE gene product was a protein of ca. 31 kilodaltons and that the pilF gene product was a protein of ca. 18 kilodaltons. We believe that the pilF gene product may act as a competitive inhibitor of pilus polymerization. Thus, pilus length may be controlled by the ratio of pilin to pilF gene product present within the cell. PMID- 2879831 TI - Inhibition of adhesive activity of K88 fibrillae by peptides derived from the K88 adhesin. AB - A cyanogen bromide fragment derived from the K88ab adhesin inhibited the hemagglutinating activity of K88 fibrillae. Smaller fragments which inhibited the adherence of K88 fibrillae to erythrocytes or to intestinal epithelial cells were obtained by digestion of K88ab fibrillae with alpha-chymotrypsin. Active peptides were isolated from the digestion mixture and identified as Ser-Leu-Phe and Ala Ile-Phe. Both tripeptides correspond to the peptide stretches Ser-148-Leu-Phe-150 and Ala-156-Ile-Phe-158, respectively, which are part of conserved regions in the primary structure of the K88 variants ab, ac, and ad. The isolated tripeptides inhibited the hemagglutinating activity of purified K88 fibrillae in the 1 to 5 microM range, while adherence of the fibrillae to intestinal epithelial cell brush borders was inhibited in the 10 to 50 microM range. Furthermore, the tripeptides were capable of eluting attached bacteria from agglutinated erythrocytes. The inhibitory activity of the isolated peptides was confirmed by testing various synthetic peptides for their ability to inhibit the interaction of the different K88 variants with various species of erythrocytes. The significance of these findings for the localization of the receptor-binding domain is discussed. PMID- 2879832 TI - Effect of clorazepate on depressed mood in anxious patients. AB - A double-blind, placebo-controlled study of clorazepate in the treatment of 189 patients diagnosed with generalized anxiety disorder was conducted to evaluate the efficacy of an anxiolytic on the depressed-mood component of anxiety. Clorazepate-treated patients with concomitant high levels of depressed mood, defined as a score of 60 or above on the Zung Self-Rating Depression Scale (SDS), showed significant improvement of anxiety symptomatology, as measured by the Hamilton Rating Scale for Anxiety and the Zung Self-Rating Anxiety Scale, and of depressed mood, as measured by the SDS, compared with placebo-treated patients (all p values less than .01). PMID- 2879833 TI - Phosphorylation state of acetyl-coenzyme A carboxylase. I. Linear inverse relationship to activity ratios at different citrate concentrations. AB - Acetyl-CoA carboxylase and its associated kinase have been purified to homogeneity from rat liver and, together with the catalytic subunit of liver protein phosphatase, used to study the effect of phosphorylation on the carboxylase activity. Phosphatase increases the carboxylase activity, whereas the kinase decreases it. A linear inverse relationship (correlation coefficient = 0.98) exists between phosphate incorporated by the kinase and the specific activity. The kinetics of activation by citrate show an increased Ka and a decreased Vmax for carboxylase preparations with increasing levels of phosphate. On this basis an enzymic test was devised for phosphate incorporated by the kinase. Thus the ratio of activities at 0 and 2 mM citrate is inversely proportional to the phosphate incorporated (correlation coefficient = -0.95), with 0.8 mol of P incorporated per mol of subunit decreasing the activity ratio from 0.5 to 0. This activity ratio method has an inherent internal control which makes it suitable for determining the level of protein-bound phosphate affecting the carboxylase activity in crude tissue extracts, and hence it should be useful for physiological studies. Tryptic maps of carboxylase labeled with radioactive phosphate by the carboxylase kinase indicate that the slightly less than 1 mol of P/mol of subunit is distributed equally between two peptides, whereas cAMP dependent protein kinase phosphorylates these two sites and a third which may not affect activity. PMID- 2879834 TI - Phosphorylation state of acetyl-coenzyme A carboxylase. II. Variation with nutritional condition. AB - Acetyl-CoA carboxylase from liver exhibits a linear inverse relationship between the ratio of enzymic activities at 0 and 2 mM citrate and the extent of phosphorylation by its kinase, and this citrate activity ratio method was used to examine the effect of nutritional conditions on the phosphorylation state of the enzyme. This method showed that the calculated phosphorylation state, being the extent of phosphorylation at sites accessible to carboxylase kinase, was highest in the livers of starved rats, lower in those fed normally, and lower still in starved rats which had been refed for 48 h on a fat-free diet. The actual values were 0.44, 0.26, and 0 mol of P/subunit, respectively, provided that liver samples were frozen rapidly to liquid nitrogen temperatures and extracted with stopping buffers at temperatures well below freezing. Normal homogenization with stopping buffers (containing inhibitors for protein kinases and phosphatases) resulted in much higher calculated phosphorylation states. The effect of nutritional conditions on the phosphorylation state as estimated reported above was confirmed by purifying the carboxylase from livers of rats, measuring the amount of phosphate which could be incorporated by carboxylase kinase, and comparing this with the phosphorylation state calculated from the citrate activity ratio method or the specific activity. Furthermore, treatment with protein phosphatase of carboxylase from starved rats resulted in the largest increase in specific activity, that from the starved/refed rats in the least. Finally, the effects of hyperglycemia on carboxylase and phosphorylase characteristics in the livers of intact rats were ascertained by taking liver samples and preparing crude extracts by the rapid freezing method described above. Hyperglycemia caused a rapid increase in the activity of the carboxylase and a rapid decrease in its putative phosphorylation state as measured by the citrate activity ratio method. Phosphorylase was also dephosphorylated, as indicated by a decrease in phosphorylase a activity. We conclude that the citrate activity ratio method is a valid test for the phosphorylation state of acetyl-CoA carboxylase in crude extracts of tissue. PMID- 2879836 TI - Developmental regulation of trypanosome mitochondrial gene expression. AB - Mitochondrial respiratory activities in the protozoan parasite Trypanosoma brucei are developmentally regulated. The trypanosomes in the mammalian bloodstream derive ATP entirely from glycolysis. The trypanosomes found in the midgut of the insect vector or in culture at 26 degrees C have fully functional mitochondria with cytochrome-mediated respiration. In this paper, we show that the steady state levels of the 9 S and 12 S mitochondrial ribosomal RNAs (rRNAs) are 30-fold lower in an early developmental stage in the mammal, the slender forms, relative to the levels in the stumpy trypanosomes, a later developmental stage in the mammalian infection. Transcripts from three other mitochondrial genes, cytochrome b and subunits I and II of cytochrome oxidase, are undetectable in the slender trypanosomes and increase in the stumpy trypanosomes to levels approaching those in trypanosomes from 26 degrees C cultures. Transcription of other mitochondrial genes, including NADH-dehydrogenase subunit 5, is unregulated during trypanosome development. These results show that the level of some mitochondrial transcripts is developmentally regulated in bloodstream trypanosomes and suggest that the stumpy bloodstream trypanosomes accumulate mitochondrial transcripts prior to development of a functional mitochondrion. These results also show that the developmental activation of mitochondrial activities at 26 degrees C is not controlled at the level of mitochondrial transcription. PMID- 2879835 TI - Transcriptional analysis of tyrosine hydroxylase gene expression in the tuberoinfundibular dopaminergic neurons of the rat arcuate nucleus after estrogen treatment. AB - The tuberoinfundibular dopaminergic neurons in the arcuate nucleus of the rat hypothalamus project to the median eminence and release dopamine from the axon terminals into the portal vessels. The released dopamine is transported to the anterior pituitary and acts to inhibit the release of prolactin from lactotrophs. About 50% of the tuberoinfundibular neurons have been shown to have estrogen receptors, and several research groups have shown that estrogen treatment affects dopamine release. Our interest is to determine, using an in vitro run-on transcription assay, whether acute estrogen treatment modulates the expression of the gene encoding for the rate-limiting enzyme for dopamine biosynthesis, tyrosine hydroxylase, in a manner parallel to the values reported for dopamine turnover. We found that after 20 min of estrogen treatment in a 3-week ovariectomized rat that tyrosine hydroxylase gene transcription decreased to 40% of control and continued to decrease after an hour of estrogen to 5% of control. After 4 days of estrogen, tyrosine hydroxylase gene transcription increased but was only about 70% of control. In contrast to the bimodal change in tyrosine hydroxylase gene transcription in response to acute estrogen, we were only able to detect a change in the levels of tyrosine hydroxylase mRNA after 2 weeks of estrogen treatment, when a 2-fold decrease was observed. Similar results for dopamine turnover, as compared to tyrosine hydroxylase gene transcription, have been reported by others in that 3 h after a single estrogen benzoate injection, dopamine turnover was decreased, while after 3 days there was not a significant change. Therefore, it seems that the changes in tyrosine hydroxylase gene transcription after acute estrogen treatment qualitatively parallel the values reported for dopamine turnover, suggesting that the rate of transcription may be an index of neural stimulation. PMID- 2879837 TI - Identification of a substrate site for liver transglutaminase on the aminopropeptide of type III collagen. AB - The aminopropeptide of type III collagen incorporates [3H]putrescine in the presence of liver transglutaminase, and the change in incorporation with concentration indicates one binding site on each of the Mr = 15,000 subunits of the peptide. At low concentrations the incorporation was comparable to that of dimethyl casein and much greater than actin or fibrinogen. Cleavage and Edman degradation of the aminopropeptide identified the major putrescine-binding site as glutamine in position 14. The surrounding amino acid sequence (Leu-Gly-Gln Ser) shows homology with some synthetic peptide substrates of transglutaminase. PMID- 2879838 TI - Short-term metabolic fate of [13N]ammonia in rat liver in vivo. AB - The short-term metabolic fate of [13N]ammonia in the livers of adult male, anesthetized rats was determined. Following a bolus injection of tracer quantities of [13N]ammonia into the portal vein, the single pass extraction was approximately 93%, in good agreement with the portal-hepatic vein difference of approximately 90%. High performance liquid chromatographic analysis of deproteinized liver samples indicated that labeled nitrogen is exchanged rapidly among components of: mitochondrial aspartate aminotransferase and glutamate dehydrogenase reactions and cytoplasmic aspartate aminotransferase and alanine aminotransferase reactions (t1/2 for the exchange of label toward equilibrium is on the order of seconds). Comparison of specific activities of glutamate and ammonia suggests that at 5 s most labeled glutamate was mitochondrial, whereas at 60 s approximately 93% was cytosolic; this change is presumably brought about by the combined action of the mitochondrial and cytosolic aspartate aminotransferases and the aspartate carrier of the malate-aspartate shuttle. Specific activity measurements of glutamate, alanine, and aspartate are in accord with the proposal by Williamson et al. (Williamson, D.H., Lopes-Vieira, O., and Walker, B. (1967) Biochem. J. 104, 497-502) that the components of the aspartate aminotransferase reaction are in thermodynamic equilibrium, whereas the components of the alanine aminotransferase reaction are in equilibrium but compartmented in the rat liver. Despite considerable label in citrulline at early time points, no radioactivity (less than or equal to 0.25% of the total) was detected in carbamyl phosphate, suggesting very efficient conversion to citrulline with little free carbamyl phosphate accumulating in the mitochondria. Our data also show that some portal vein-derived ammonia is metabolized to glutamine in the rat liver, but the amount is small (approximately 7% of that metabolized to urea) in part because liver glutamine synthetase is located in a small population of perivenous cells "downstream" from the urea cycle-containing periportal cells. Finally, no tracer evidence could be found for the participation of the purine nucleotide cycle in ammonia production from aspartate. The present work continues to emphasize the usefulness of [13N]ammonia for short-term metabolic studies under truly tracer conditions, particularly when turnover times are on the order of seconds. PMID- 2879839 TI - Intracellular distribution of mammalian stress proteins. Effects of cytoskeletal specific agents. AB - Following a brief period of heat stress, the two highly conserved mammalian stress proteins, hsp68 and 70, were examined with respect to their intracellular locations. In four independent cell lines, hsp68 and 70 were found to partition into both Triton X-100-soluble and insoluble fractions as assessed by two dimensional gel analysis of newly synthesized polypeptides, whereas a fifth cell line showed these proteins only in the Triton X-100-insoluble fraction. In addition, a previously described cell fractionation technique was utilized to gain information regarding the segregation of the two major mammalian stress proteins, hsp68 and 70, into distinct biochemically and morphologically characterized subcellular compartments of PtK2-epithelial cells. Two cytoskeletal specific agents, taxol and colchicine, were also probed for their effects on the disposition of these polypeptides. Under our conditions of acute heat exposure, hsp68, 70 and their isoforms were globally distributed in all subcellular fractions examined, with a few notable exceptions in drug-treated cells. Colchicine, a microtubule-depolymerizing drug, inhibited the association of hsp68 and its variants with the double-detergent-extractable labile "cytoskeleton," whereas taxol, a microtubule-stabilizing agent, in some manner, facilitated the transit of hsp68 and its isovariants from a cytoplasmic to nuclear domain. Degree of cell density is a factor which influences the synthesis of various cytoskeletal proteins; therefore, we studied the effect of cell confluency on the disposition of mammalian stress proteins hsp68 and 70 in human FS-4 fibroblasts. In confluent cultures, where cell-cell contact was maximal, we observed the appearance of a previously undetected polypeptide which was not found in sparsely populated cultures. This protein may represent a post-translationally modified isoform of a preexisting heat shock protein, or perhaps, a novel stress protein. PMID- 2879840 TI - Inactivation of pea seed glutamine synthetase by the toxin, tabtoxinine-beta lactam. AB - Glutamine synthetase of plants is the physiological target of tabtoxinine-beta lactam, a toxin produced by several disease-causing pathovars of Pseudomonas syringae. This toxin, a unique amino acid, is an active site-directed, irreversible inhibitor of glutamine synthetase from pea. ATP is required for inactivation. Neither ADP, AMP, nor adenosine 5'-(beta,gamma methylene)triphosphate (AMP-PCP) supports inactivation. Adenyl-5'-yl imidophosphate (AMP-PNP) is slowly hydrolyzed by glutamine synthetase to produce adenyl-5'-yl phosphoramidate (AMP-PN) and inorganic phosphate as identified by 31P NMR spectroscopic analysis. AMP-PNP also supports a slow inactivation of glutamine synthetase by tabtoxinine-beta-lactam. These data are consistent with gamma-phosphate transfer being involved in the inactivation. Completely inactivated glutamine synthetase has 0.9 mumol of toxin bound/mumol of subunit. One mumol of ATP is bound per mumol of subunit of glutamine synthetase in the absence of either the toxin or another active site-directed inhibitor, methionine sulfoximine; whereas, a 2nd mumol of either [alpha- or gamma-32P]ATP is bound per mumol of subunit when glutamine synthetase is incubated in the presence of either toxin or methionine sulfoximine until all enzyme activity is lost. These data suggest that the gamma-phosphate hydrolyzed from ATP during inactivation remains with the enzyme-inhibitor complex, as well as the ADP. The open chain form, tabtoxinine, was neither a reversible nor an irreversible inhibitor of glutamine synthetase, suggesting that the beta-lactam ring is necessary for inhibition. The inactivation of glutamine synthetase with tabtoxinine-beta-lactam is pseudo-first order when done in buffer containing 15% (v/v) ethylene glycol. The rate constant for this reaction is 3 X 10(-2) S-1, and the Ki for the toxin is 1 mM. Removal of the ethylene glycol from the buffer allows the reaction to proceed in a non-first order manner with the apparent rate constant decreasing with time. As the enzyme is inactivated in these conditions, the binding affinity for the toxin appears to decrease, while the Km observed for glutamate does not change. PMID- 2879841 TI - Chemical modification and labeling of glutamate residues at the stilbenedisulfonate site of human red blood cell band 3 protein. AB - A new method has been developed for the chemical modification and labeling of carboxyl groups in proteins. Carboxyl groups are activated with Woodward's reagent K (N-ethyl-5-phenylisoxazolium 3'-sulfonate), and the adducts are reduced with [3H]BH4. The method has been applied to the anion transport protein of the human red blood cell (band 3). Woodward's reagent K is a reasonably potent inhibitor of band 3-mediated anion transport; a 5-min exposure of intact cells to 2 mM reagent at pH 6.5 produces 80% inhibition of transport. The inhibition is a consequence of modification of residues that can be protected by 4,4' dinitrostilbene-2,2'-disulfonate. Treatment of intact cells with Woodward's reagent K followed by B3H4 causes extensive labeling of band 3, with minimal labeling of intracellular proteins such as spectrin. Proteolytic digestion of the labeled protein reveals that both the 60- and the 35-kDa chymotryptic fragments are labeled and that the labeling of each is inhibitable by stilbenedisulfonate. If the reduction is performed at neutral pH the major labeled product is the primary alcohol corresponding to the original carboxylic acid. Liquid chromatography of acid hydrolysates of labeled affinity-purified band 3 shows that glutamate but not aspartate residues have been converted into the hydroxyl derivative. This is the first demonstration of the conversion of a glutamate carboxyl group to an alcohol in a protein. The labeling experiments reveal that there are two glutamate residues that are sufficiently close to the stilbenedisulfonate site for their labeling to be blocked by 4,4' diisothiocyanodihydrostilbene-2,2'-disulfonate and 4,4'-dinitrostilbene-2,2' disulfonate. PMID- 2879842 TI - Characterization of thrombospondin as a substrate for factor XIII transglutaminase. AB - Thrombin activation of platelets induces the release of a high molecular weight glycoprotein, thrombospondin. On treatment with factor XIII transglutaminase and [3H]putrescine, thrombospondin undergoes specific incorporation of this labeled amine, with 2-3 mol of putrescine being incorporated per mol of thrombospondin. Analysis of plasmin digests of [3H]putrescine-thrombospondin showed that the Mr 53,000-core peptide contains the glutamine site for amine incorporation. In the absence of amine substrate, thrombospondin was found to provide both donor (glutamine) and acceptor (lysine) sites for intermolecular cross-links by factors XIIIa, and high molecular weight protein complexes were formed. Homopolymers of thrombospondin were also observed by electron microscopy. Thrombin-cleaved thrombospondin has more cross-linking sites accessible for [3H]putrescine incorporation or for cross-linkage to itself than does the uncleaved native protein. Examination of thrombospondin cross-linkage in the presence of other protein substrates (fibronectin, collagen, fibrinogen, and von Willebrand factor) for factor XIIIa, resulted in reduced thrombospondin polymer formation. Electron microscopy and autoradiography of fibrin clots formed in the presence of 125I thrombospondin showed an association of thrombospondin with fibrin fibrils. However, confirmation that this association involves covalent epsilon-(gamma glutamyl)lysyl cross-links between thrombospondin and fibrin was not obtained. PMID- 2879843 TI - Glucagon gene transcription in an islet cell line is regulated via a protein kinase C-activated pathway. AB - Proglucagon is a polyprotein precursor containing not only glucagon and glicentin, but glucagon-like peptides-I and -II and an intervening peptide (IP II). The glucagon gene is expressed in both pancreatic islets and neuroendocrine L-cells of the gastrointestinal tract. We have recently cloned an islet cell line from a rat pancreatic islet cell tumour that simultaneously expresses the glucagon, insulin, somatostatin, and angiotensinogen genes. We investigated the potential role of "second messenger" pathways in the regulation of glucagon gene expression. Both the tumor promoter agent phorbol myristate acetate (PMA) and a diacylglycerol analog, 1,2-dioctanoylglycerol, induced a 2.7- and 2.5-fold increase in steady-state glucagon mRNA levels at 24 h, respectively. The increase was progressive up to 24 h and was specific for glucagon mRNA; the insulin and somatostatin mRNA levels remained unchanged. An inactive phorbol ester, 4 beta phorbol 12,13,20-triacetate, was without effect. The glucagon mRNA increase induced by PMA was mediated through an increase in glucagon gene transcription reaching maximal stimulation at 30-60 min. Glucagon mRNA half-life was similar in both control and PMA-treated cells, approximating 12 h. The stimulation of glucagon gene transcription was accompanied by a corresponding 3-fold increase in proglucagon biosynthesis. Neither dibutyryl cAMP nor glucocorticoids affected glucagon mRNA levels, while inducing a 5-fold increase in somatostatin mRNA levels and 4.8-fold stimulation in angiotensinogen mRNA at 24 h, respectively. We conclude that expression of the glucagon gene in this islet cell line is regulated at the level of transcription through a protein kinase C (Ca2+/phospholipid-dependent enzyme)-activated pathway. PMID- 2879844 TI - Identification of a guanosine triphosphate-binding site on guinea pig liver transglutaminase. Role of GTP and calcium ions in modulating activity. AB - Guanosine 5'-triphosphate (GTP) was found to inhibit guinea pig liver transglutaminase activity as measured by [3H]putrescine incorporation into casein. GDP and GTP-gamma-S also inhibited enzyme activity (GTP-gamma-S greater than GTP greater than GDP). Kinetic studies showed that GTP acted as a reversible, noncompetitive inhibitor and that CaCl2 partially reversed GTP inhibition. GTP also inhibited rat liver and adult bovine aortic endothelial cell transglutaminase, but did not inhibit Factor XIIIa activity. Guanosine monophosphate (GMP), cyclic GMP, and polyguanylic acid did not inhibit enzyme activity. Guinea pig liver transglutaminase adsorbed well to GTP-agarose affinity columns, but not to CTP-agarose columns, and the binding was inhibited by the presence of calcium ions. Specific binding of GTP to transglutaminase was demonstrated by photoaffinity labeling with 8-azidoguanosine 5'-[gamma-32P] triphosphate, which was inhibited by the presence of GTP or CaCl2. GTP inhibited trypsin proteolysis of guinea pig liver transglutaminase without affecting the trypsin proteolysis of chromogenic substrates. Proteolytic protection was reversed by the addition of calcium. This study demonstrates that GTP binds to transglutaminase and that both GTP and calcium ions function in concert to regulate transglutaminase structure and function. PMID- 2879845 TI - Microtubule-acting drugs lead to the nonpolarized delivery of the influenza hemagglutinin to the cell surface of polarized Madin-Darby canine kidney cells. AB - The synchronized directed transfer of the envelope glycoproteins of the influenza and vesicular stomatitis viruses from the Golgi apparatus to the apical and basolateral surfaces, respectively, of polarized Madin-Darby canine kidney (MDCK) cells can be achieved using temperature-sensitive mutant viruses and appropriate temperature shift protocols (Rindler, M. J., I. E. Ivanov, H. Plesken, and D. D. Sabatini, 1985, J. Cell Biol., 100:136-151). The microtubule-depolymerizing agents colchicine and nocodazole, as well as the microtubule assembly-promoting drug taxol, were found to interfere with the normal polarized delivery and exclusive segregation of hemagglutinin (HA) to the apical surface but not with the delivery and initial accumulation of G on the basolateral surface. Immunofluorescence analysis of permeabilized monolayers of influenza-infected MDCK cells treated with the microtubule-acting drugs demonstrated the presence of substantial amounts of HA protein on both the apical and basolateral surfaces. Moreover, in cells infected with the wild-type influenza virus, particles budded from both surfaces. Viral counts in electron micrographs showed that approximately 40% of the released viral particles accumulated in the intercellular spaces or were trapped between the cell and monolayer and the collagen support as compared to less than 1% on the basolateral surface of untreated infected cells. The effect of the microtubule inhibitors was not a result of a rapid redistribution of glycoprotein molecules initially delivered to the apical surface since a redistribution was not observed when the inhibitors were added to the cells after the HA was permitted to reach the apical surface at the permissive temperature and the synthesis of new HA was inhibited with cycloheximide. The altered segregation of the HA protein that occurs may result from the dispersal of the Golgi apparatus induced by the inhibitors or from the disruption of putative microtubules containing tracks that could direct vesicles from the trans Golgi apparatus to the cell surface. Since the vesicular stomatitis virus G protein is basolaterally segregated even when the Golgi elements are dispersed and hypothetical tracks disrupted, it appears that the two viral envelope glycoproteins are segregated by fundamentally different mechanisms and that the apical surface may be incapable of accepting vesicles carrying the G protein. PMID- 2879846 TI - Microtubules containing acetylated alpha-tubulin in mammalian cells in culture. AB - The subcellular distribution of microtubules containing acetylated alpha-tubulin in mammalian cells in culture was analyzed with 6-11B-1, a monoclonal antibody specific for acetylated alpha-tubulin. Cultures of 3T3, HeLa, and PtK2 cells were grown on coverslips and observed by immunofluorescence microscopy after double staining by 6-11B-1 and B-5-1-2, a monoclonal antibody specific for all alpha tubulins. The antibody 6-11B-1 binds to primary cilia, centrioles, mitotic spindles, midbodies, and to subsets of cytoplasmic microtubules in 3T3 and HeLa cells, but not in PtK2 cells. These observations confirm that the acetylation of alpha-tubulin is a modification occurring in different microtubule structures and in a variety of eukaryotic cells. Some features of the acetylation of cytoplasmic microtubules of mammalian cells are also described here. First, acetylated alpha tubulin is present in microtubules that, under depolymerizing conditions, are more stable than the majority of cytoplasmic microtubules. In addition to the specific microtubule frameworks already mentioned, cytoplasmic microtubules resistant to nocodazole or colchicine, but not cold-resistant microtubules, contain more acetylated alpha-tubulin than the rest of cellular microtubules. Second, the alpha-tubulin in all cytoplasmic microtubules of 3T3 and HeLa cells becomes acetylated in the presence of taxol, a drug that stabilizes microtubules. Third, acetylation and deacetylation of cytoplasmic microtubules are reversible in cells released from exposure to 0 degrees C or antimitotic drugs. Fourth, the epitope recognized by the antibody 6-11B-1 is not absolutely necessary for cell growth and division. This epitope is absent in PtK2 cells. The acetylation of alpha-tubulin could regulate the presence of microtubules in specific intracellular spaces by selective stabilization. PMID- 2879847 TI - Topography of cell wall lytic enzyme in Chlamydomonas reinhardtii: form and location of the stored enzyme in vegetative cell and gamete. AB - Chlamydomonas lytic enzyme of the cell wall (gamete wall-autolysin) is responsible for shedding of cell walls during mating of opposite mating-type gametes. This paper reports some topographic aspects of lytic enzyme in cells. Both vegetative and gametic cells contain the same wall lytic enzyme. The purified enzyme is a glycoprotein with an apparent molecular mass of 67 kD by gel filtration and 62 kD by SDS PAGE, and is sensitive to metal ion chelators and SH blocking agents. These properties are the same as those of the gamete wall autolysin released into the medium by mating gametes. However, the storage form of the enzyme proves to be quite different between the two cell types. In vegetative cells, the lytic enzyme is found in an insoluble form in cell homogenates and activity is released into the soluble fraction only by sonicating the homogenates or freeze-thawing the cells, whereas gametes always yield lytic activity in the soluble fractions of cell homogenates. When vegetative cells are starved for nitrogen, the storage form of enzyme shifts from its vegetative state to gametic state in parallel with the acquisition of mating ability. Adding nitrogen to gametes converts it to the vegetative state concurrently with the loss of mating ability. We also show that protoplasts obtained by treatment of vegetative cells or gametes with exogenously added enzyme have little activity of enzyme in the cell homogenates, suggesting that lytic enzyme is stored outside the plasmalemma. When the de-walled gametes or gametes of the wall-deficient mutant, cw-15, of opposite mating types are mixed together, they mate normally but the release of lytic enzyme into the medium is practically negligible. When the de-walled vegetative cells are incubated, the lytic enzyme is again accumulated in the cells after the wall regeneration is almost complete. PMID- 2879848 TI - Intracellular distribution of active and inactive transglutaminase in stimulated cultured C6 glioma cells. AB - The cellular distribution of active and inactive transglutaminase (TGase) was studied in C6 glioma cells before and during stimulation by a serum-containing medium. The activity of the enzyme was determined in the soluble and insoluble fractions obtained by freezing and thawing the cells, followed by centrifugation at 12,000g for 5 min. In the soluble fractions, the activity of TGase decreased 2.5 h post-stimulation and increased after 5 and 8 h. In the corresponding insoluble fractions, no significant changes in the activity of the enzyme were noted up to 8 h after stimulating the cells with fresh medium. An immunological approach was next used to determine the quantity of TGase antigen during the stimulation of the cultured glioma cells. In the soluble fraction, the quantity of the antigen decreases significantly at 2.5, 5, and 8 h. In contrast, in the insoluble fraction, a significant increase in TGase antigen was detected 8 h after the addition of fresh medium. Cycloheximide completely inhibited the increase in the quantity of TGase antigen in the insoluble fraction, 8 h post stimulation, while actinomycin D caused a partial inhibition. Trypsin, neuraminidase, or Sendai viruses increased the activity of TGase significantly, when added to nonstimulated cells. Trypsin had no effect on TGase activity when added to the cells 2 h after stimulation with a serum-containing medium. These findings suggest that an inactive form of the enzyme is present in the insoluble cellular fraction. A model has been proposed to explain the variations in TGase activity, its distribution and translocation during cellular stimulation. PMID- 2879849 TI - Effect of taxol on first and second meiotic spindle formation in oocytes of the surf clam, Spisula solidissima. AB - The effect of taxol on first and second meiotic spindle formation was examined in oocytes of the surf clam, Spisula solidissima, by immunofluorescence staining with anti-tubulin antibody. The first meiotic spindle appeared to form as in untreated control cells. However, the spindle did not migrate toward the periphery of taxol-activated oocytes, resulting in blockage of the formation of the first polar body. In spite of inhibited microtubule depolymerization and failure of spindle disappearance, the pole separation in telophase that is typical of this material began at the same time as in untreated cells. Polymerization of the second spindle microtubules onto the spindle persisting from the first meiosis led to the formation of a triple form of spindle connected at the poles of each other. The subsequent emergence of ring-shaped microtubule containing structures in mature activated eggs was not affected by taxol. The mechanism of meiotic spindle formation thus seemsto be different from that in mitosis, where taxol has been shown to block spindle formation completely. PMID- 2879850 TI - Reversibility of hemodynamic hypofrontality in schizophrenia. AB - Regional cerebral blood flow (CBF) was studied in 51 young schizophrenics. A significant decrease of CBF was seen in frontal and prefrontal regions (hypofrontal pattern) in chronic patients whose disease had evolved for more than 2 years and who were in remission. This hypofrontal pattern was reversible, as it disappeared during exacerbation of the disease. In 10 patients who had not been treated with neuroleptics for several weeks, we found a dopaminergic hypersensitivity in the frontal lobes, as a weak dose of piribedil restored near normal frontality. This may reflect either the role of neuroleptic washout or a primitive dopaminergic depletion, as proposed by some authors in the chronic form of schizophrenia. PMID- 2879851 TI - Beta-adrenergic agonists increase lung liquid clearance in anesthetized sheep. AB - We did experiments to determine whether beta-adrenergic agonists increase lung liquid clearance in anesthetized ventilated adult sheep and, if so, whether the increase is mediated by beta receptors and what mechanism is involved. We instilled 100 ml of autologous serum either alone or with a beta-adrenergic agonist (terbutaline, 10(-5) M, or epinephrine, 5.5 X 10(-6) M) into one lower lobe. After 4 h both terbutaline and epinephrine increased lung liquid clearance. The increase in lung liquid clearance was inhibited when propranolol (a beta blocker) or amiloride (a sodium channel blocker) was added to the terbutaline. Increased clearance was not explained by changes in pulmonary hemodynamics, pulmonary blood flow, or lung lymph flow. We conclude that beta-adrenergic agonists increase lung liquid clearance in anesthetized intact adult sheep. This increase is mediated through beta receptors and probably depends on increased active transport of sodium across the alveolar barrier. PMID- 2879852 TI - Multipotential phenotypic expression of genes encoding peptide hormones in rat insulinoma cell lines. AB - The developmental origin of the four phenotypically distinct hormone-producing islet cells (insulin, glucagon, somatostatin, pancreatic polypeptide) is unclear. To investigate the potential for phenotypic differentiation of islet cells, we prepared several clonal cell lines from a radiation-induced rat islet tumor and analyzed them for insulin, glucagon, and somatostatin gene expression by cDNA hybridization, immunocytochemistry, and radioimmunoassay. We found expression of all three genes in the tumor and in the parental cell line and mixed variable phenotypes in the clonal lines derived from the parental line. We also observed the ectopic expression of the angiotensinogen gene in the tumor and the cell lines. The relative levels of hormonal gene expression differed among the cell lines but remained fixed during continuous passage. The three islet hormone mRNAs were larger compared to the pancreas owing to longer poly(A) tracts. These observations indicate that neoplastic islet cells retain the potential to differentiate into hormone-specific cellular phenotypes and may mimic developmental pathways of the pancreatic islets. PMID- 2879853 TI - Hepatic glucagon metabolism. Correlation of hormone processing by isolated canine hepatocytes with glucagon metabolism in man and in the dog. AB - We have found that canine and rat hepatocytes convert (125I)iodoTyr10-glucagon to a peptide metabolite lacking the NH2-terminal three residues of the hormone. The peptide is released into the cell incubation medium and its formation is unaffected by a variety of lysosomotropic or other agents. Use of specific radioimmunoassays and gel filtration demonstrated in both normal subjects and in chronic renal failure patients a plasma peptide having the properties of the hormone fragment identified by cell studies. Studies of the dog revealed a positive gradient of the fragment across the liver and no differential gradient of the fragment and glucagon across the kidney. We conclude that the glucagon fragment arises from the cell-mediated processing of the hormone on a superficial aspect of the hepatocyte, the glucagon fragment identified during experiments in vitro represents the cognate of a peptide formed during the hepatic metabolism of glucagon in vivo, and measurement of the fragment by COOH-terminal radioimmunoassays could lead to an understimulation of hepatic glucagon extraction. PMID- 2879854 TI - Importance of the route of intravenous glucose delivery to hepatic glucose balance in the conscious dog. AB - To assess the importance of the route of glucose delivery in determining net hepatic glucose balance (NHGB) eight conscious overnight-fasted dogs were given glucose via the portal or a peripheral vein. NHGB was measured using the arteriovenous difference technique during a control and two 90-min glucose infusion periods. The sequence of infusions was randomized. Insulin and glucagon were held at constant basal levels using somatostatin and intraportal insulin and glucagon infusions during the control, portal, and peripheral glucose infusion periods (7 +/- 1, 7 +/- 1, 7 +/- 1 microU/ml; 100 +/- 3, 101 +/- 6, 101 +/- 3 pg/ml, respectively). In the three periods the hepatic blood flow, glucose infusion rate, arterial glucose level, hepatic glucose load, arterial-portal glucose difference and NHGB were 37 +/- 1, 34 +/- 1, 32 +/- 3 ml/kg per min; 0 +/ 0, 4.51 +/- 0.57, 4.23 +/- 0.34 mg/kg per min; 101 +/- 5, 200 +/- 15, 217 +/- 13 mg/dl; 28.5 +/- 3.5, 57.2 +/- 6.7, 54.0 +/- 6.4 mg/kg per min; +2 +/- 1, -22 +/- 3, +4 +/- 1 mg/dl; and 2.22 +/- 0.28, -1.41 +/- 0.31, and 0.08 +/- 0.23 mg/kg per min, respectively. Thus when glucose was delivered via a peripheral vein the liver did not take up glucose but when a similar glucose load was delivered intraportally the liver took up 32% (P less than 0.01) of it. In conclusion portal glucose delivery provides a signal important for the normal hepatic peripheral distribution of a glucose load. PMID- 2879855 TI - Physicians' attitudes toward pain in children. AB - Physicians' attitudes toward pain in children were assessed in an attempt to explain why adults are administered more analgesics than children while in the hospital. A survey was conducted of all pediatricians, family practitioners, and surgeons in Hartford. Fifty-seven percent of the sample responded (112/195). Seventy-five percent of the sample felt that children experienced adult-like pain by age 2. Thirty-eight percent of the physicians were somewhat or significantly concerned about the risk of addiction when using narcotics in their young patients. Pediatricians were significantly more likely than surgeons or family practitioners to see younger children as having adult-like pain and to prescribe analgesics for children at an earlier age. Many other attitudinal differences were also related to specialty. Other demographic variables (age, sex, mode of practice, and personal experience with pain) had little effect on attitudes. These findings suggest possible explanations for the discrepancy between child and adult analgesic prescribing practices. PMID- 2879857 TI - Benzodiazepine use in psychiatrically hospitalized elderly patients. PMID- 2879856 TI - The effect of neuroleptics and other psychotropic drugs on negative symptoms in schizophrenia. AB - It has been hypothesized that the negative symptoms of schizophrenia are related to structural brain abnormalities and respond poorly to treatment with neuroleptics and other drugs since they are persistent, if not irreversible. Because this issue has important clinical and theoretical implications, the authors reviewed the relevant literature on the effect of neuroleptics, L-dopa, and other psychotropic agents on these symptoms. Contrary to the above conclusions, several large scale, controlled studies of the therapeutic effects of conventional neuroleptics have reported clinically relevant improvement in negative symptoms in a significant proportion of schizophrenics. The improvement tended to occur early in the course of treatment and was most notable in those patients with relatively shorter durations of illness. A specific class of neuroleptic drugs not studied in these earlier large scale trials, the diphenylbutylpiperidines, has been suggested to be particularly likely to ameliorate negative symptoms, possibly because of their significant calcium channel blocking action. A review of the clinical studies comparing this group of neuroleptics with those from different classes supports the suggestion that they can produce greater improvement in anergia and emotional withdrawal. Six open and four controlled trials of L-dopa treatment of negative symptoms with L-dopa alone or in combination with neuroleptics. As with neuroleptics alone, improvement tended to be greater in those with a shorter duration of illness. The available evidence suggests that negative symptoms, at least in less chronic schizophrenic patients, may be partially responsive to currently available pharmacological intervention in a significant proportion of schizophrenics. PMID- 2879858 TI - Post-partum psychoses and the dexamethasone suppression test. AB - The hypothesis that post-partum psychoses are predominantly mixed affective disorders was tested by administering the dexamethasone suppression test (DST) to seven puerperal psychotics, six puerperal depressives and comparison groups of non-puerperal psychotic and depressed women. The hypothesis received support from the finding that two-third of the puerperal patients had positive DSTs versus one third of similar non-puerperal patients. An 80% rate of positive DSTs in 19 normal women 5 days post-partum, however, suggested this was an invalid interpretation of this finding, particularly as the majority of these tests returned to normal when repeated several weeks later. PMID- 2879859 TI - Classification of anxiety disorders: a critique of DSM-III. PMID- 2879860 TI - Dentistry on stamps. PMID- 2879861 TI - The physics, pathophysiology, and management of high velocity gunshot wounds. AB - The authors report on a gunshot wound of the foot with subsequent infection and nonunion. The pathophysiology of a gunshot wound is discussed with special emphasis on the temporary cavity and permanent cavity produced, and how this affects skin, subcutaneous tissue, muscle, and bone. The prognosis of a given wound is also determined by a thorough examination of the bullet design, its velocity, and potential for tissue disruption. Proper management of the wound is discussed relative to debridement technique and surgical care. Four principles of management for gunshot wounds include recognition or diagnosis, reduction, retention or immobilization, and restoration of function. Some of the pitfalls are discussed including inadequate assessment of the wound relating to its extent and mismanagement. PMID- 2879862 TI - Collagenous colitis and pulmonary fibrosis. Manifestations of a single disease? AB - A 66-year-old man developed chronic watery diarrhea and progressive dyspnea over 1-year. Colonic biopsy revealed a thickened subepithelial collagen layer consistent with collagenous colitis; open lung biopsy revealed pulmonary fibrosis. Only one previous report links extraintestinal manifestations to collagenous colitis. Although the patient had been taking sulfasalazine, the case supports the idea that collagenous colitis, like inflammatory bowel disease, is part of a systemic disorder. PMID- 2879863 TI - Efficacy of fish larvivore, Gambusia affinis for the control of mosquito breeding in wells in semi-urban areas near Delhi. PMID- 2879864 TI - Integrated approach to the management of pain. A National Institutes of Health consensus report synopsis. PMID- 2879865 TI - Specific inhibition of hybrid resistance in F1 hybrid mice pretreated with parent strain spleen cells. I. Induction of a nylon-adherent, Thy-1+Lyt-1+2- suppressor cell. AB - Hybrid resistance, which is observed in certain strain combinations when parent strain bone marrow cells are grafted into lethally irradiated F1 hybrids, can be specifically overcome by the i.v. injection, 1 wk before the graft, of spleen cells syngeneic with the bone marrow graft. This phenomenon is due to a suppressor mechanism, induced in the spleen of the F1 hybrid by the injection of parent-strain spleen cells and mediated by a nylon-adherent Thy-1+Lyt-1+2- cell population of hybrid origin, because hybrid resistance can be inhibited by the transfer into a normal B6D2F1 of nylon-adherent Thy-1+Lyt-1+2- spleen cells from B6D2F1 mice pretreated with B6 spleen cells 1 wk earlier (B6-pretreated B6D2F1); spleen cells from B6-pretreated B6D2F1 mice not depleted of their nylon-adherent subpopulation cannot restore hybrid resistance when they are injected into a B6D2F1 rendered nonresistant by split-dose irradiation; and spleen cells from normal B6D2F1 mice cannot restore hybrid resistance when they are injected into B6-pretreated B6D2F1 hybrids. The suppressor cells specifically inhibit resistance against bone marrow cells syngeneic with the spleen cells used for pretreatment, because transfer of nylon-adherent B6-pretreated B6D2F1 spleen cells into a normal B6D2F1 does not enhance syngeneic B6D2F1 or parent-strain D2 bone marrow growth, and when injected into normal B6D2F1 hybrids, nylon-adherent spleen cells from B6D2F1 mice pretreated with D2 spleen cells 1 wk earlier (D2 pretreated B6D2F1) are not able to transfer the inhibition of hybrid resistance against B6 bone marrow cells. Moreover, the activity of the suppressor cells depends on the genetic environment of the hybrid host mice, because nylon adherent B6-pretreated B6D2F1 spleen cells injected into normal B6C3F1 hybrids do not transfer an inhibition of hybrid resistance, and when injected into B6C3F1 hosts previously rendered nonresistant by split-dose irradiation, spleen cells from B6-pretreated B6D2F1 mice can, in contrast, transfer hybrid resistance. PMID- 2879866 TI - Cell kinetics in the fetal mouse thymus: precursor cell input, proliferation, and emigration. AB - The entry and differentiation of lymphoid precursor cells (LPC) in grafted mouse fetal thymuses and the emigration of explants thymocytes has been followed in a system in which donor and host lymphocytes could be distinguished on the basis of Thy-1 expression. It appears that LPC that invade the fetal mouse thymus between 10 and 13 days rapidly differentiate into Thy-1 positive thymocytes, giving rise to all of the lymphoid populations of both cortical and medullary locations until approximately the end of the first week after birth. Lymphoid precursor cells that enter the fetal thymus after 13 days of fetal life only differentiate into Thy-1 positive lymphocytes 6 or 7 days after birth, when they give rise to a second generation of thymocytes that grows exponentially and completely replaces the first generation in approximately 8 days. All cells leaving the thymus during the first 2 wk of life appear to be derived from the first wave of precursors. PMID- 2879867 TI - The localization of the antibody response in milk or bile depends on the nature of the antigen. AB - Immunization in the Peyer's patches of rats with horse spleen ferritin or Escherichia coli 06 carrying type 1 pili resulted in an IgA antibody response detected in milk and bile and an IgG and IgM antibody response in serum, milk, and bile. The IgA antibody response to type 1 pili was as a mean 5.0-fold higher in milk than in bile. In contrast IgA antibody activity to 06 LPS was as a mean 6.3-fold higher in bile than in milk. The IgA antibodies to ferritin were randomly distributed between milk and bile. The IgG and IgM antibody activity to all three antigens studied were higher in the milk than in the bile. The secretory antibody response could be transferred from immunized rats to unimmunized rats with mesenteric lymph node cells (MLN) taken from donor rats 4 days after immunization in the Peyer's patches. IgA antibodies to pili and ferritin appeared solely in the milk of the recipients, whereas IgA antibodies to the 06 LPS only appeared in the bile. The ratios serum:milk and serum:bile for the IgG and IgM antibodies indicated an antigen-specific direction of homing with local production of these two isotypes primarily in the mammary gland. Antibody forming cells of the IgA class could not be detected in the MLN on the day the cells were transferred. It is concluded that the difference seen in antibody distribution between milk and bile is not due to dissemination of antigen, but instead a result of different homing or expansion at the mucosal-glandular site dependent on the antigen specificity of the migrating cells. PMID- 2879868 TI - Limited diversity and selection of rearranged gamma genes in polyclonal T cells. AB - The role of a T gamma gene product in the immune response is not known. To investigate the participation of the T gamma gene in functional T cells, we estimated its variable (V gamma) gene diversity among mature polyclonal T cells and assayed for in vivo selection of rearranged V gamma genes during the immune response. In this study, we present evidence that functionally mature, normal human T cells have rearranged their T gamma genes but display a limited range of gene rearrangement choices. In contrast to clonal T cell neoplasms, an invariant array of seven T gamma gene rearrangements was found to be proportionately distributed within normal polyclonal T cell populations, as well as in benign polyclonal T cell proliferations incited by a wide variety of pathological conditions. Findings presented here indicate that the likelihood of rearrangement of each human V gamma gene may be fixed. Lack of selection of V gamma genes during the mature T cell immune response implies a limited role of any single V gamma gene at this stage of T cell development. PMID- 2879869 TI - Genomic DNA encoding rabbit T cell receptor beta-chains: isotypes and allotypes of C beta. AB - We have discovered sequence differences in DNA encoding the first exon of rabbit T cell receptor beta-chains from unrelated rabbits that probably reflect allelic C beta 1 allotypes. Rabbit I was from a colony bred to maintain the K1-expression mutation Basilea, and rabbit II was from a colony bred to maintain the K1b9 allotype. Genomic DNA from rabbits I and II also exhibit restriction fragment length polymorphism of C beta on Southern blots. In addition, several different restriction enzyme digests of DNA from rabbit I give three bands, whereas DNA from rabbit II gives two when probed with C beta. An approximately 14-kb cloned genomic DNA fragment from rabbit I has two copies of C beta exon 1 and a 6-kb fragment has a third copy, suggesting that rabbit I has three different C beta genes. The DNA sequence of a germ-line genomic DNA fragment encoding the first exon of the beta-chain constant region from rabbit I also has an open reading frame encoding 140 amino acids immediately 5' of the C beta sequence. A corresponding sequence had previously been found in a cDNA clone from the second rabbit (rabbit II). PMID- 2879870 TI - Lymphokine-activated killer (LAK) cells. II. Delineation of distinct murine LAK precursor subpopulations. AB - Lymphokine-activated killer (LAK) cells can lyse a number of tumor target cells regardless of whether the tumors are natural killer (NK) sensitive or resistant. LAK can also lyse autologous lymphoblasts that have been modified with 2,4,6 trinitrobenzene sulfonic acid (TNBS). In this study, we examined the surface markers of murine LAK precursors. It was found that depletion of Thy 1- or Lyt 2 bearing precursor cells abolished the ability of spleen cells to generate LAK against TNBS-self, but had no effect on the generation of LAK against tumor cells. Depletion of asialo-GM1 (AGM1)-bearing precursors abolished the generation of LAK against all target cells tested. Normal spleen cells were fractionated on a Percoll density gradient and two fractions were examined: fraction (Fxn) 3, which is enriched for NK activity but depleted of the ability to generate cytotoxic T lymphocytes (CTL), and Fxn 5, which had no NK activity but was enriched for the ability to generate CTL. Both fractions were capable of generating LAK, although Fxn 5 required a relatively larger amount of interleukin 2 (IL 2). Upon examination of the surface markers of LAK precursors in these fractions it was found that the precursors in Fxn 3 giving rise to LAK against tumors were Thy-1-, Lyt-2-, AGM1+, whereas the precursors in Fxn 5 were Thy-1+, Lyt-2+, AGM1+. The precursors generating LAK against TNBS-self were Thy-1+, Lyt 2+, AGM1+ in both fractions. The time kinetics of LAK generation in both fractions were different, with Fxn 3 showing much earlier kinetics. These data delineate at least two different LAK precursors defined by their buoyant density, by their surface markers, and by their susceptible target cells. These data also may resolve the confusion in the literature regarding the phenotype of LAK precursors. PMID- 2879872 TI - Coordinated multicenter study of norfloxacin versus trimethoprim-sulfamethoxazole treatment of symptomatic urinary tract infections. The Urinary Tract Infection Study Group. AB - In a coordinated, double-blind multicenter trial among general practitioners, 2,255 consecutive patients with symptoms suggesting urinary tract infection were screened; 886 were randomized to receive 200 mg of norfloxacin (333 patients), 400 mg of norfloxacin (335), or 160 mg/800 mg of trimethoprim-sulfamethoxazole (TMP-SMZ; 218) twice daily for seven days. We analyzed bacteriologic efficacy for 252, 240, and 141 of the patients receiving 200 mg of norfloxacin, 400 mg of norfloxacin, or TMP-SMZ, respectively. The short-term efficacy was 97.5%-98.6%, and the accumulated efficacy was 87.9%-88.8%. In patients with complicated infections and in men, the efficacy for the group receiving 200 mg of norfloxacin was lower than that for the other groups. In patients with recurrent infection, bacterial elimination was greater for those receiving TMP-SMZ. Significantly fewer adverse reactions occurred in patients receiving norfloxacin than in those treated with TMP-SMZ. The 200-mg dosage of norfloxacin seemed to cause fewer side effects than the 400-mg dosage. PMID- 2879871 TI - Effect of cyclophosphamide on T-lymphocyte marker expression in T-cell areas of some lymphoid organs of the rat. AB - Surface markers on rat lymphocytes from thymus and T-cell areas of lymph node, spleen and Peyer's patches were examined in histological sections after one single dose of Cyclophosphamide (CY, 100 mg/kg body weight). A panel of monoclonal antibodies was used: W3/13, W3/25 and OX8 to investigate Pan T, TH and Ts/c marker expressions respectively. Ts/c marker expression showed a marked and significant reduction in both thymus and lymph node lymphocytes 3 days after CY treatment. This was followed by return to normal in the thymus and a significant rebound increase in the lymph node by day 7 after treatment. This Ts/c marker expression in both the spleen and Peyer's patches showed a significant increase on both day 3 and 7 after CY treatment. Mast cells were observed in large numbers in the thymus and lymph node but not in the spleen and Peyer's patches. TH marker expression was increased significantly in lymph nodes, spleen and Peyer's patches. No change was observed in Pan T marker expression in any of the tissues at any of the times examined. PMID- 2879874 TI - Epidemiology of nephropathia epidemica in Sweden. AB - A comprehensive study of nephropathia epidemica (NE), caused by Puumala virus, was conducted in Sweden. Human sera from residents of various regions of Sweden were examined for antibody to Puumala virus, and the incidence of NE was determined. Small mammals were captured at locations throughout Sweden and were examined for antibody to Puumala virus and for antigen. The human serosurvey found the highest prevalence rates and the highest incidence rates in northern Sweden. The bank vole was found to be the most-abundant rodent, as well as the species most frequently positive for antibody. Antibody-positive voles were restricted to the northern two-thirds of the country, an area corresponding to that where most human disease was noted. These results suggest that the bank vole is the principal host of Puumala virus in Sweden and clearly establish the region near 64 degrees N as highly endemic for NE in humans. PMID- 2879873 TI - Comparison of clindamycin, rifampin, tetracycline, metronidazole, and penicillin for efficacy in prevention of experimental gas gangrene due to Clostridium perfringens. AB - Gas gangrene caused by Clostridium perfringens is associated with significant mortality and morbidity in spite of penicillin treatment. Although prompt surgical debridement has been established as the primary therapeutic objective, additional studies are needed for determination of the optimal antimicrobial therapy. In a mouse model of gas gangrene caused by Clostridium perfringens, clindamycin, metronidazole, rifampin, and tetracycline were all more efficacious than penicillin (P less than .05). Survival of penicillin-treated mice was not significantly better than that of untreated controls in spite of serum levels that ranged up to 77-1,800 micrograms/ml. Responses to metronidazole were highly dose dependent. For example, 60% of mice survived after 75 mg of metronidazole/kg, but only 10% survived after 19 mg/kg. In contrast, clindamycin was highly effective over a broad dosing range (8.6-86 mg/kg). The efficacy of all antibiotics was reduced if treatment was delayed or larger inocula of bacteria were used. PMID- 2879875 TI - [Search for possible routes of vertical infection of adult T-cell leukemia virus (ATLV): evidence of viral transmission from mother to child]. AB - Adult T-cell leukemia (ATL) in Japan is remarkably concentrated in adult T-cell leukemia virus (ATLV)-endemic areas and this limited distribution and other epidemiological analysis have strongly suggested the possibility of familial spreading of ATLV. I am interested in whether ATLV can be transmitted from mother to child and the possible routes of vertical infection of ATLV. I report here the results of a study on them. The results were as follows: No ATLV antigen-positive cells were detected at birth or 1, 3 or 6 months after birth. However, at later stages, the viral antigen-bearing cells became detectable. In 19 of 23 infants examined, the ATLV-positive cells were detected at 9 to 36 months after birth. The titers of antibodies to ATLV in the pairs of samples from mothers and their infants at birth were virtually equal, as expected. After birth, the titer of maternally derived antibody in all infants decreased gradually, and it disappeared within 3 to 9 months. However, ATLV-antibody reappeared in 12 of 24 infants examined, being detected after 12 months old. Further, it was shown that all breast milk samples derived from 12 seropositive mothers contained the ATLV which was capable of being transmitted to peripheral leukocytes of neonates. PMID- 2879876 TI - [Increased creatine phosphokinase (CPK) level and muscle symptoms during beta blocker therapy]. PMID- 2879877 TI - Computer applications in intravenous anaesthetic administration. AB - The place of computerization in intravenous anaesthesia delivery: Although total intravenous anaesthesia may have advantages over inhalational anaesthesia in certain circumstances, it has drawbacks from the point of view of feedback control. The ideal agent is not available, although di-isopropylphenol holds promise. There is an undefinable end-point. Inadequate dosage produces the extremely unpleasant phenomenon of intra-operative awareness. Future developments, it seems, should include the development of suitable intravenous agents and transducers of anaesthetic depth, rather than increasingly complicated control systems. It is extremely unlikely that a computer will replace the anaesthetist in the foreseeable future. The anaesthetist is still required for, amongst other things, specifying the desired depth of anaesthesia and varying it during the operation, and for responding to unforeseen crises. It may be hoped that, by liberating the anaesthetist from those tasks which can be automated, more time can be devoted to patient monitoring and other aspects of anaesthetic care, thereby improving patient safety. There is an undoubted place for computerized delivery of anaesthesia in teaching (particularly teaching pharmacokinetic principles) and in research (for standardization of anaesthetic depth). PMID- 2879878 TI - Beta blockers and the neutrophil. PMID- 2879879 TI - Educating family physicians to care for the chronically mentally ill. AB - More than 50 percent of the chronically mentally ill receive their medical, psychiatric, and social support services from primary care physicians in the general health sector. Despite this high level of involvement with these patients, the majority of family physicians consider their training in the management of patients with mental disorders to be inadequate. This paper describes six categories of critical competencies that should be included in the mental health curricula of family physician training programs: therapeutic attitudes and skills, diagnosis and differential diagnosis, functional assessment, psychopharmacology, management of emergencies, and psychosocial treatments. It outlines the manner in which specific competencies could be incorporated in medical school, in family practice residency training, and in postgraduate continuing medical education as well as the specific elements included in each. The discussion is based on the assumption that more effective participation by family physicians in the treatment of chronic psychiatric illness requires active attention throughout the continuum of medical education. PMID- 2879880 TI - Depression, parkinsonian symptoms, and negative symptoms in schizophrenics treated with neuroleptics. AB - To determine whether depression and neuroleptic-induced parkinsonism confound the clinical assessment of negative symptoms in schizophrenics, we evaluated 45 outpatient schizophrenics for depression, parkinsonian symptoms, and negative symptoms using standard clinical rating scales. Neuroleptic and anticholinergic dose and plasma activity were also determined. Associations between negative symptoms and these clinical and drug variables were examined using a multivariate statistical model. Negative symptoms were significantly correlated with several parkinsonian symptoms, some vegetative features of depression, and with anticholinergic dose. No significant correlations were found between negative symptoms and cognitive features of depression, or neuroleptic and anticholinergic plasma activity. These findings suggest that assessment criteria for negative symptoms, depression, and drug-induced parkinsonism overlap in treated schizophrenics. Strategies for differentiating these clinical syndromes are discussed. PMID- 2879882 TI - The placebo effect in agoraphobia. AB - This paper presents two sets of data that suggests a weak but specific placebo response in agoraphobia. First, analyses in 20 agoraphobic patients given single blind placebo over a 2-week period, without the customary confound of instructions for exposure to phobic situations, revealed a statistically significant reduction in panic and phobic symptoms. However, symptoms remained in the moderate to severe range and functioning was virtually unchanged. Second, comparisons between six agoraphobic patients receiving double-blind placebo and six others receiving "no pills," matched for age, sex and exposure treatment, revealed a significant placebo effect over an 8-week period. Implications for clinical research are briefly discussed. PMID- 2879881 TI - The aftermath of rape. Profiles of immediate and delayed treatment seekers. AB - Seventy-eight sexual assault victims who sought treatment within 1 month of their assaults were compared with 40 victims who delayed seeking treatment. Demographic, rape situation, and psychiatric history characteristics were examined as were postrape symptom profiles and responses to treatment. More of the delayed treatment seekers were raped by a "friend," and fewer used physical means to defend themselves against the assailant. With respect to symptomatology, delayed treatment seekers reported considerable rape-related distress and were more anxious and significantly more fearful than were recent rape victims. Implications for clinical practice and for the tailoring of services for victims of sexual assault are suggested. PMID- 2879883 TI - Differential action of bromocriptine on nigrostriatal versus mesolimbic dopaminergic neurons. AB - The present study was undertaken to compare the abilities of the dopaminergic agonists apomorphine, bromocriptine, and lergotrile to inhibit the synthesis of dopamine (DA) in terminals of nigrostriatal and mesolimbic DA neurons. The in vivo synthesis of DA was estimated by measuring the rate of accumulation of dihydroxyphenylalanine (DOPA) in terminals of nigrostriatal (striatum) and mesolimbic (nucleus accumbens, olfactory tubercle) neurons 30 min after the administration of NSD 1015, a decarboxylase inhibitor. The activation of DA autoreceptors in these regions was evaluated by measuring the abilities of the DA agonists to inhibit DA synthesis in brain regions of rats pretreated with gamma butyrolactone (GBL). Apomorphine (0.03-1.0 mg/kg for 45 min) and bromocriptine (0.1-10 mg/kg for 90 min) produced dose-dependent decreases in the rate of DA synthesis in all three brain regions of both vehicle- and GBL-treated rats. A time course of the effects of the highest dose of bromocriptine (10 mg/kg), however, demonstrated dramatic regional differences in the ability of this drug to inhibit DA synthesis in saline-versus GBL-pretreated rats. Bromocriptine inhibited the GBL-induced increase in DA synthesis for 6 hours in all regions examined. In the striatum of saline-treated rats the decrease in DA synthesis was evident only at 1.5 hours after bromocriptine administration, while in the nucleus accumbens and olfactory tubercle DA synthesis remained inhibited for 6 hours. By contrast, lergotrile reduced DA synthesis to a similar extent in all three regions for at least 6 hours in both vehicle- and GBL-treated rats. These results suggest that there is no regional difference in the ability of bromocriptine to inhibit DA synthesis via DA autoreceptor mechanisms, but there appear to be differences in postsynaptic DA receptor-mediated mechanisms which regulate nigrostriatal versus mesolimbic DA neurons. PMID- 2879884 TI - Alpha-1 and alpha-2 adrenoceptor binding in cerebral cortex: competition studies with [3H]prazosin and [3H]idazoxan. AB - The tritiated adrenergic antagonists prazosin ([3H]PRZ) and idazoxan ([3H]IDA, or RX-781094) bind specifically and with high affinity in membrane preparations from cerebral cortex to alpha-1- and alpha-2-adrenoceptors respectively. Saturation experiments, performed to determine the density of receptors (Bmax; maximum binding capacity) and the dissociation constant (Kd 25 degrees C), were analyzed by the methods of Eadie and Hofstee, iterative modelling, and the procedure of Hill. The pharmacologic properties and specificity of the labelling was verified by displacement experiments using alpha-adrenergic antagonists and agonists. The antagonist drugs showed the following order of potency to displace [3H]prazosin: prazosin much greater than phentolamine much greater than corynanthine greater than pyrextramine much greater than yohimbine much greater than piperoxan greater than benextramine greater than idazoxan; for the agonists: clonidine much greater than (-)-noradrenaline much greater than (-)-adrenaline much greater than phenylephrine, while other drugs, such as (-)-propranolol, dopamine, (-) isoproterenol and serotonin only competed with the alpha-1-ligand at concentrations above 20 microM. The alpha 2-sites labelled by [3H]idazoxan were characterized by the antagonist displacement sequence idazoxan much greater than phentolamine greater than yohimbine = greater than piperoxan much greater than pyrextramine much greater than benextramine much greater than prazosin much greater than corynanthine. The agonists order of potency to compete with [3H]idazoxan was clonidine much greater than phenylephrine = greater than (-) adrenaline greater than (-)-noradrenaline, and for other related drugs it was (-) propranolol much greater than dopamine much greater than serotonin greater than ( )-isoproterenol. These competition experiments clearly showed two pharmacologically distinct sites, but question the relative specificity of some of the adrenergic drugs. PMID- 2879885 TI - Day-night rhythm of rat pineal tyrosine hydroxylase activity as determined by HPLC with amperometric detection. AB - Tyrosine hydroxylase activity in the rat pineal gland was measured by means of HPLC determination of the amount of L-3,4-dihydroxyphenylalanine formed. Enzyme activity showed a clear day-night rhythm, paralleling that of plasma melatonin levels in the same animals, with values being high during the dark period apparently because of changes in Vmax. In animals maintained under constant illumination for 3 days, tyrosine hydroxylase activity and plasma melatonin level rhythms were completely abolished, a result indicating that both are under photoperiodic control. PMID- 2879886 TI - Posttranslational protein modification by polyamines in intact and regenerating nerves. AB - A 150,000-g supernatant from axoplasm of the giant axon of the stellate nerve of the squid and from rat sciatic and goldfish optic nerves was found to be able to incorporate covalently [3H]putrescine and [3H]spermidine into an exogenous protein (N,N'-dimethylcasein). Incorporation of radioactivity was inhibited by CuSO4, a specific inhibitor of transglutaminases, the enzymes mediating these reactions in other tissues. Analysis of pH and temperature range and enzyme kinetics displayed characteristics predicted for transglutaminase-mediated reactions. Transglutaminase activity increased during regeneration of both vertebrate nerves, but greater activity was found in segments of nerve containing no intact axons than in either intact segments or in segments containing regenerating axons. Polyacrylamide gel electrophoresis of endogenous modified proteins (in the absence of N,N'-dimethylcasein) showed labeling of 18-, 46- and 200-kilodalton proteins by both [3H]putrescine and [3H]spermidine. Analysis of the protein-bound radioactivity from intact and regenerating rat sciatic nerves demonstrated it to be predominantly in the form of the parent radioactive polyamine. These experiments demonstrate the covalent modification of proteins by polyamines at low levels in squid axoplasm and at relatively higher levels in rat sciatic and goldfish optic nerves. In the latter two cases, the activity of these modification reactions may be due in part to the modification of axonal proteins, but the majority of the activity occurs in nonneuronal cells of the nerve. PMID- 2879888 TI - In vivo studies on the extracellular, and veratrine-releasable, pools of endogenous amino acids in the rat striatum: effects of corticostriatal deafferentation and kainic acid lesion. AB - The effects of corticostriatal deafferentation (decortication) and destruction of intrinsic neurons (intrastriatal kainate injection) on the extracellular concentration, and veratrine-releasable pools, of endogenous amino acids in the rat striatum were examined using the in vivo brain dialysis technique. Intracellular amino acid content was also determined. Decortication reduced selectively intra- and extracellular levels of glutamate (Glu) and aspartate (Asp). Extracellular changes were more pronounced than those in tissue content. gamma-Aminobutyric acid (GABA), taurine (Tau), and phosphoethanolamine (PEA) levels were not affected, whereas nonneuroactive amino acids were increased at 1 week but not at 1 month post-lesion. The intracellular pool of Glu and Asp was also reduced in kainate-lesioned striata. However, extracellular levels of these compounds were not affected significantly by this treatment. The tissue content of all other amino acids was decreased, the most prominent change being in the concentration of GABA. Extracellular GABA concentration was also reduced dramatically, whereas the concentrations of noneuroactive amino acids were increased to varying degrees. These data suggest that transmitter pools of neuroactive amino acids are an important supply for their extracellular pools. Lesion-induced alterations in nonneuroactive amino acids are discussed with regard to the loss of metabolic pools, glial reactivity, and changes in blood brain barrier transport. Veratrine induced a massive release of neuroactive amino acids such as Glu, Asp, GABA, and Tau into the extracellular fluid, and a delayed increase in PEA. Extracellular levels of neuroactive amino acids were raised slightly. Decortication reduced, selectively, the amounts of Glu and Asp released by veratrine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879887 TI - Active site studies on a narrow-specificity thyroliberin-hydrolysing pyroglutamate aminopeptidase purified from synaptosomal membrane of guinea-pig brain. AB - The effect of protein-modifying reagents on the activity of a purified preparation of a thyroliberin-hydrolysing pyroglutamate aminopeptidase, solubilised from synaptosomal membranes of guinea-pig brain by treatment with papain, was investigated. The results indicated that tyrosine, histidine, arginine, and possibly lysine residues were necessary for expression of catalytic activity and that these tyrosine, histidine, and arginine residues were probably located at the active site of the enzyme. Cysteine, serine, glutamate, and aspartate residues were not involved in the expression of catalytic activity. PMID- 2879890 TI - The acute effect of ammonium acetate on levels of amino acids in the intact and decorticated rat neostriatum. AB - Unilateral frontal cortex ablations were performed in rats so that the glutamate terminals in the ipsilateral rostral neostriatum were removed. At 1 or 7 days later, intraperitoneal injections of ammonium acetate induced different changes in amino acid concentrations in the intact and deafferentated neostriatum. After 1 day, the level of glutamate decreased only in the intact side, whereas that of glutamine increased and that of aspartate decreased to the same extent on both sides following ammonia injection. After 7 days, the glutamate level decreased more in the intact than the decorticated side in both nonconvulsing and convulsing rats. The concentration of alanine increased most in the intact neostriatum, whereas glutamine levels increased and aspartate levels decreased to the same extent on both sides in nonconvulsing and convulsing rats. The results indicate that ammonia has a more pronounced effect on neuronal than glial glutamate pools. PMID- 2879889 TI - Cellular origins of endogenous amino acids released into the extracellular fluid of the rat striatum during severe insulin-induced hypoglycemia. AB - The effect of severe insulin-induced hypoglycemia on the extracellular levels of endogenous amino acids in the rat striatum was examined using the brain microdialysis technique. A characteristic pattern of alterations consisting of a 9-12-fold increase in aspartate (Asp), and more moderate increases in glutamate (Glu), taurine (Tau), and gamma-aminobutyric acid (GABA), was noted following cessation of electroencephalographic activity (isoelectricity). Glutamine (Gln) levels were reduced both during and after the isoelectric period and there was a delayed increase in extracellular phosphoethanolamine (PEA) content. The effects of decortication and excitotoxin lesions on the severe hypoglycemia-evoked efflux of endogenous amino acids in the striatum were also examined. Decortication reduced the release of Glu and Asp both 1 week and 1 month post-lesion. The efflux of other neuroactive amino acids was not affected significantly. In contrast, GABA, Tau, and PEA efflux was attenuated in kainate-lesioned striata. Glu and Asp release was also reduced under these conditions, and a smaller decrease in extracellular Gln was noted. These data suggest that GABA, Glu, and Asp are released primarily from their transmitter pools during severe hypoglycemia. The releasable pools of Tau and PEA appear to be located in kainate sensitive striatal neurons. The significance of these results is discussed with regard to the excitotoxic theory of hypoglycemic cell death. PMID- 2879891 TI - Tyrosine hydroxylase, tryptophan hydroxylase, biopterin, and neopterin in the brains of normal controls and patients with senile dementia of Alzheimer type. AB - The activities of tyrosine hydroxylase and tryptophan hydroxylase, and the concentrations of the biopterin cofactor and the precursor neopterin were measured in 14 regions of postmortem brains from four histologically verified patients of senile dementia of the Alzheimer type (SDAT) and eight histologically normal controls. Neopterin concentrations were measured in the human brain for the first time. The activities of tyrosine hydroxylase and tryptophan hydroxylase in the brains of patients with SDAT were significantly reduced in the substantia nigra and in the lateral segment of the globus pallidus, locus ceruleus, and substantia nigra, respectively. The concentrations of total biopterin in the brains of patients with SDAT were significantly reduced in the putamen and substantia nigra, but the total neopterin concentrations did not change significantly. These results suggest that the reduction in biogenic amines in SDAT might be related to reductions in biosynthetic enzymes associated with biogenic amines, due to destruction of monoaminergic neurons. PMID- 2879892 TI - Phosphorylation of tyrosine hydroxylase by cyclic GMP-dependent protein kinase. AB - Tyrosine hydroxylase purified from rat pheochromocytoma was phosphorylated and activated by purified cyclic GMP-dependent protein kinase as well as by cyclic AMP-dependent protein kinase catalytic subunit. The extent of activation was correlated with the degree of phosphate incorporated into the enzyme. Comparable stoichiometric ratios (0.6 mol phosphate/mol tyrosine hydroxylase subunit) were obtained at maximal concentrations of either cyclic AMP-dependent or cyclic GMP dependent protein kinases. The enzymes appeared to mediate the phosphorylation of the same residue based on the observation that incorporation was not increased when both enzymes were present. The major tryptic phosphopeptide obtained from tyrosine hydroxylase phosphorylated by each protein kinase exhibited an identical retention time following HPLC. The purified phosphopeptides also exhibited identical isoelectric points. These data provide support for the notion that the protein kinases are phosphorylating the same residue of tyrosine hydroxylase. PMID- 2879894 TI - Somatostatin and Alzheimer's disease: a hypothesis. AB - Recent data suggest a disturbance of some brain somatostatin neurons in Alzheimer's disease. Moreover, some endocrine activities known to be regulated by somatostatin, such as growth hormone, thyroid-stimulating-hormone, somatomedins, as well as insulin and glucose metabolism, also seem to be affected in some patients. It is speculated that these changes are due to a global CNS and endocrine somatostatin defect in Alzheimer's disease and that the described endocrine imbalance may indirectly be responsible for at least part of the CNS pathology. PMID- 2879893 TI - Magnesium ions inhibit the stimulation of inositol phospholipid hydrolysis by endogenous excitatory amino acids in primary cultures of cerebellar granule cells. AB - Omission of Mg2+ from the incubation buffer results in a six- to eightfold increase in [3H]inositol-1-phosphate ([3H]Ins-1-P) accumulation in primary cultures of cerebellar granule cells at 7-9 days in vitro. This increase is reversed by low concentrations of 2-amino-5-phosphono-valerate (APV), a result indicating that the absence of Mg2+ facilitates the activation of a specific receptor by the endogenous excitatory amino acids (presumably L-glutamate and L aspartate) released from the granule cells. The absence of Mg2+ also potentiates the action of exogenously applied N-methyl-D-aspartate (NMDA), L-glutamate, L aspartate, and kainate. In contrast, the action of quisqualate is virtually unaffected by Mg2+ and is resistant to APV inhibition. Addition of the depolarizing agent veratridine enhances the accumulation of [3H]Ins-1-P also in Mg2+-containing buffer. The action of veratridine is antagonized by APV, a result suggesting that, under depolarized conditions, the NMDA receptor can be activated by the endogenously released excitatory amino acids, despite the presence of Mg2+. Accordingly, in the presence of Mg2+, veratridine potentiates the action of exogenously applied NMDA but does not facilitate the action of quisqualate. PMID- 2879895 TI - Newly synthesized catalytic and regulatory components of adenylate cyclase are expressed in neurites of cultured sympathetic neurons. AB - Forskolin- and guanine nucleotide-stimulated adenylate cyclase activities were measured in microdissected sections of neurites from small explants and in dispersed cell cultures of sympathetic ganglion neurons to determine whether a competent system for regulated formation of cAMP, consisting of both catalytic units of adenylate cyclase and regulatory GTP binding proteins, is synthesized during neurite outgrowth and where it is distributed in the neuron. An increase in both guanine nucleotide- and forskolin-dependent activity of adenylate cyclase occurred concomitantly with neurite outgrowth and was directly proportional to neurite length. Separate analysis of adenylate cyclase activity in explant cell bodies or neurites showed that the increased activity was localized entirely in the neurites, while activity in the cell bodies remained virtually constant during growth. Concentric sections of neurites of approximately 500 microns width, which contained similar volumes of neurites as determined with the indicator BCECF (Rink et al., 1982), produced similar levels of cAMP, indicating an even distribution of adenylate cyclase in the neurites. Cell bodies, when stimulated by GTP gamma S, produced 236 +/- 46 attomol cAMP/min (30 degrees C)/cell body and an additional 52.6 +/- 20 attomol cAMP/min (30 degrees C)/neuron were produced with each day of neurite growth (approximately 400 microns). Assuming a turnover number of 2000 min-1, cell bodies and neurites were calculated to contain similar densities of catalytic unit molecules on their surface (9-28 molecules/micron 2). An abundant GTP binding protein, detected by ADP-ribosylation with pertussis toxin, was also widely distributed in the neuron.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879896 TI - The distribution of tyrosine hydroxylase-immunoreactive fibers in primate neocortex is widespread but regionally specific. AB - An antiserum directed against tyrosine hydroxylase (TH), an enzyme involved in dopamine and norepinephrine synthesis, was used to visualize axons immunohistochemically in monkey neocortex. Labeled fibers were distributed throughout the entire neocortex, but they had striking patterns of regional and laminar specialization. For example, primary motor cortex contained the greatest density of TH-labeled fibers, whereas primary sensory regions were sparsely innervated. Marked heterogeneity of fiber density was also present among the association regions of the frontal, parietal, and temporal lobes. In addition, the laminar pattern of innervation in a given region was correlated with its fiber density. Sparsely innervated regions had labeled fibers only in layer I and sometimes layer VI. In regions of intermediate density, labeled fibers tended to be located in layers I-superficial III and layers V-VI, whereas in densely innervated motor cortex TH-immunoreactive fibers were present in all cortical layers. Comparison of these distribution patterns with those produced by an antiserum directed against dopamine-beta-hydroxylase (DBH), a specific marker of neocortical noradrenergic axons, revealed marked differences. DBH-immunoreactive fibers were observed in some cortical locations where few or no TH-labeled fibers were present. In other regions, the density of TH-immunoreactive processes far exceeded that of DBH-labeled fibers. These findings indicate that nearly all of the immunoreactive fibers revealed by this anti-TH antiserum are dopaminergic. This interpretation was further supported by lesions of the ascending noradrenergic fibers in the brain stem, which reduced DBH immunoreactivity, but not TH immunoreactivity, in neocortex. The distinctive innervation patterns of TH immunoreactive fibers suggest a functional specialization of the dopaminergic projections to primate neocortex. PMID- 2879897 TI - Production, characterization, and immunohistochemical application of monoclonal antibodies to glutaminase purified from rat brain. AB - Monoclonal antibodies were produced against phosphate-activated glutaminase (EC 3.5.1.2) as a marker for glutamatergic neurons: The enzyme was purified 1000-fold from rat brain mitochondria with a recovery of 27%. Upon SDS-PAGE the purified enzyme showed a single band up to 1.7 micrograms after the silver staining at molecular weight 62,000. Two monoclonal antibodies (IgMs) were produced; these absorbed more than 90% of glutaminase activity in rat brain homogenate. In immunoblotting after PAGE of the homogenate, the antibodies recognized only 1 protein band at the same position as that of the purified enzyme. Thus, the antibodies are specific and sufficient markers for glutaminase. Many neuronal cells in the rat brain were labeled immunohistochemically with these antibodies, but non-neuronal elements such as glial cells and vessels were not. Intense labeling was consistently observed in putative glutamatergic neurons such as pyramidal cells of layers V and VI in the cerebral neocortex. Intense staining was also seen in possible mossy fiber endings in the granular layer of the cerebellar cortex and in neurons giving off mossy fibers such as those in the pontine nuclei, pontine tegmental reticular nucleus of Bechterew, lateral reticular nucleus of the medulla oblongata, and external cuneate nucleus. PMID- 2879898 TI - Excitatory amino acid receptors coupled with guanylate cyclase in primary cultures of cerebellar granule cells. AB - Primary cultures of cerebellar granule cells have been used in pharmacologically and functionally characterizing excitatory amino acid recognition sites coupled with guanylate cyclase. When granule cells were incubated in physiological culture conditions (Locke's solution, pH 7.4), only kainate and, to a lesser extent, L-glutamate increased cyclic GMP (cGMP) levels. Under these conditions, L aspartate, N-methyl-D-aspartate (NMDA), and quisqualate were inactive. When granule cells were incubated in the absence of extracellular Mg2+ or in the presence of the depolarizing agent veratrine, L-glutamate, L-aspartate, and NMDA became as effective as kainate in enhancing cGMP formation. The action of kainate was preferentially antagonized by 2,3-cis-piperidindicarboxylate, whereas the action of L-glutamate was preferentially antagonized by (+/-)2-amino-5 phosphonovalerate. These data suggest that 2 different excitatory amino acid recognition sites (activated by kainate or by L-glutamate, L-aspartate, and NMDA, respectively) are coupled with guanylate cyclase in primary cultures of cerebellar granule cells: While the coupling of the recognition site for kainate with guanylate cyclase operates under resting conditions and in the presence of Mg2+, the coupling of the recognition site for L-glutamate, L-aspartate, and NMDA with guanylate cyclase requires depolarizing conditions or the absence of extracellular Mg2+. PMID- 2879900 TI - Recombinant DNA and the physician. PMID- 2879899 TI - Diets varying in linoleic and linolenic acid content alter liver plasma membrane lipid composition and glucagon-stimulated adenylate cyclase activity. AB - Male Sprague-Dawley rats were fed diets varying in fatty acid composition for 24 d. Liver plasma membranes were isolated, and the effect of diet on phospholipid fatty acyl tail composition and glucagon-stimulated adenylate cyclase activity was measured. Dietary linolenic acid influenced membrane phospholipid fatty acid composition and altered the effect of different dietary levels of linoleic acid on membrane composition. At low dietary intakes of linolenic acid, membrane fatty acids derived from linolenic acid increased as dietary intake of C18:2(9,12) increased. At high dietary linolenic acid levels membrane content of fatty acids derived from linolenic acid decreased as dietary intake of linoleic acid increased. Glucagon-stimulated adenylate cyclase activity decreased at high levels of both dietary linoleic acid and linolenic acid. These observations suggest that dietary balance between linoleic and linolenic acids has a role in plasma membrane composition and may control glucagon-stimulated adenylate cyclase activity. PMID- 2879901 TI - Receptor-mediated pharmacodynamics of prednisolone in the rat. AB - A pharmacokinetic/pharmacodynamic model describing receptor-mediated effects of prednisolone is presented. The basis of the model is the generally accepted mechanism of action of steroid hormones in which corticosteroids bind to cytosolic receptors forming steroid-receptor complexes, which are activated and translocated into the nucleus. There the complexes associate with specific DNA sequences and modulate the rate of transcription of DNA into specific RNAs that code for the synthesis of proteins that elicit biological responses. Prednisolone, 5 or 50 mg/kg, was administered intravenously to adrenalectomized rats. Total plasma, free plasma, CBG-free plasma, and liver prednisolone concentrations were measured simultaneously with free hepatic cytosolic glucocorticoid receptor concentrations and tyrosine aminotransferase (TAT) activity of the liver as a function of time. The association/dissociation kinetics of prednisolone binding to the glucocorticoid receptor were measured separately in vitro at 37 degrees C. Total plasma, free plasma, and CBG-free plasma prednisolone concentrations could be used equally well in the model to account for the time course of receptor concentrations and TAT activity. However, use of liver steroid concentrations resulted in an overestimation of receptor depletion. Steroid concentrations in plasma increased 20 to 30-fold with a tenfold increase in dose, but receptor occupancy and TAT activity over time increased about threefold. While prednisolone pharmacokinetics were dose dependent, parameters describing receptor kinetics and TAT activity were constant at each prednisolone dose. The major determinants of receptor-mediated glucocorticoid activity are confirmed to be the availability of the receptor, drug-receptor dissociation rate, and corticosteroid persistence in the biophase. PMID- 2879902 TI - Characterization and inhibition of mephenytoin 4-hydroxylase activity in human liver microsomes. AB - The in vivo metabolism in humans of the anticonvulsant mephenytoin exhibits stereoselectivity as well as genetic polymorphism of the 4-hydroxylation pathway. The characteristics of the involved cytochrome P-450 isozyme are, however, not known completely. Accordingly, the ability of human liver microsomes to metabolize mephenytoin and its enantiomers was investigated in vitro, and the ability of related anticonvulsants and other compounds to inhibit 4-hydroxylation was studied. Marked stereoselectivity was observed in the conversion of S mephenytoin to its 4-hydroxy metabolite, but N-demethylation was essentially similar for both enantiomers. The intrinsic clearance (Vmax/Km) for 4 hydroxymephenytoin formation showed an almost 10-fold range in five livers and was 150- to 1000-fold greater than that for N-demethylation. Competitive inhibition of 4-hydroxylation was observed with ethotoin, mephobarbital, methsuximide and phensuximide, but not other commonly used anticonvulsants such as ethosuximide, phenobarbital, phenytoin and primidone. However, synthetic N alkyl analogs of the latter compounds were found to be inhibitory. An aryl residue alpha to the carbonyl carbon of an N-alkyl lactam in a 5- or 6-membered ring, therefore, appears to be a minimal requirement for strong interaction with the 4-hydroxylase. Warfarin, but not diazepam, ketoconazole or iodochlorohydroxyquin, were also competitive inhibitors, but at much higher concentrations than the anticonvulsants. Competitive inhibition at concentrations similar to the Km of 4-hydroxymephenytoin formation (30-350 microM) may indicate that the isozyme is involved in the metabolism of the substrates under consideration and, therefore, their in vivo metabolism may be regulated to some extent by the same genetic factor(s) that determine mephenytoin's biotransformation. PMID- 2879903 TI - Pharmacological characterization of spinal alpha adrenoceptors related to blood pressure control in rats. AB - The effects of various alpha adrenoceptor agonists and antagonists injected into the spinal subarachnoid space on blood pressure and heart rate were investigated in pentobarbital-anesthetized male rats. A dose-dependent decrease in blood pressure and heart rate was induced by intrathecal injections of clonidine (0.3-3 micrograms), at the T6-T7 level. Guanabenz (3-30 micrograms) and an azepine derivative B-HT 920 (1-3 micrograms) also reduced blood pressure and heart rate. In contrast, an imidazolidine derivative St 587 (10 micrograms) was ineffective. The clonidine-induced hypotensive effect was antagonized by yohimbine but not by prazosin. Yohimbine (3-10 micrograms) alone caused an increase in blood pressure and heart rate while only a weak hypotenion occurred with prazosin (10 micrograms). Pretreatment with intrathecal 6-hydroxydopamine (50 micrograms X 2) did not impair the hypotensive action of clonidine (1 microgram) whereas the hypertensive effect of yohimbine was reduced markedly by this treatment. When injected i.v. or intrathecally at the C1-C2 level, clonidine (1 microgram) produced only a slight decrease in blood pressure. It is concluded that, in rat spinal cord, alpha-2 adrenoceptors located postsynaptically are involved in blood pressure control. Endogenous catecholamines, especially norepinephrine in the spinal cord seem to activate tonically the alpha-2 adrenoceptors. PMID- 2879904 TI - Renal toxicity of cadmium-metallothionein and enzymuria in rats. AB - The mechanism of cadmium metallothionein (Cd-MT)-induced renal toxicity was studied in rats using urinary enzyme excretion as a marker for cellular damage. Animals were injected with either saline or Zn (20 mg of Zn as ZnSO4/kg b.wt.) at 0.5, 4 or 24 hr before injection of Cd-MT (0.3 mg of Cd as Cd-MT/kg b.wt. i.p.). Activities of two brush border enzymes, alkaline phosphatase (ALP) and gamma glutamyl-transpeptidase (GGT), and a lysosomal enzyme, N-acetyl-beta-D glucosaminidase (NAG), were measured in 24-hr urine collections. Urinary excretion of all three enzymes was increased significantly after Cd-MT injection. Both ALP and GGT excretions reached a maximum at 24 hr whereas NAG excretion reached peak values at 48 hr after Cd-MT injection. The excretion of all three enzymes decreased to the control level by the 3rd day. Zn pretreatment alone had no effect on urinary enzyme excretion. Pretreatment with Zn salts at 0.5 and 2 hr before Cd-MT injection did not show any difference in the urinary excretion of the enzymes as compared with the saline-treated controls. However, injection of Zn salts at 24 hr before Cd-MT injection resulted in a significant decrease in the excretion of the lysosomal enzyme NAG whereas both ALP and GGT excretions were unchanged. Extensive proximal tubular damage was observed morphologically in all the rats injected with Cd-MT, but the cellular damage was less in rats pretreated with Zn sulfate 24 hr before Cd-MT injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879905 TI - Effect of dopamine receptor activation on ganglionic transmission and cyclic AMP levels in the stellate ganglia and renal arteries of the dog. AB - By using selective dopamine (DA) receptor agonists and antagonists, we have demonstrated previously the presence of DA-2- and DA-1-like DA receptors in the stellate ganglia of the dog. Activation of either DA-2- or DA-1-like receptors by quinpirole or fenoldopam, respectively, leads to inhibition of ganglionic transmission. In the present study we have examined the involvement of DA receptor subtypes in the action of DA on ganglionic transmission. Inasmuch as stimulation of DA receptors is linked to the activation (DA-1) or inhibition (DA 2) of the enzyme adenylate cyclase, we have also measured the accumulation of cyclic AMP (cAMP) for biochemical characterization of ganglionic DA receptors. In isolated stellate ganglia treated with phentolamine and propranolol, DA caused concentration-dependent inhibition of ganglionic transmission as evidenced by reductions in the amplitude of the evoked postganglionic compound action potentials. The inhibitory effect of DA on ganglionic transmission was antagonized by both the DA-1 receptor antagonist, R-sulpiride, and the DA-2 receptor antagonist, S-sulpiride. However, the more potent and selective DA-1 receptor antagonist, SCH-23390, failed to antagonize the DA-induced inhibition of ganglionic transmission. Isolated stellate ganglia were also utilized for the measurement of cAMP. Neither DA nor the selective DA-1 receptor agonist, fenoldopam, caused any significant changes in cAMP, suggesting the lack of an adenylate cyclase-linked DA-1 receptor in the ganglia. On the other hand, beta adrenoceptor activation by isoproterenol produced a 3-fold increase in cAMP content of the stellate ganglia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879907 TI - Behavioral effects of the beta-carboline derivatives ZK 93423 and ZK 91296 in squirrel monkeys: comparison with lorazepam and suriclone. AB - Behavioral effects of the beta-carboline derivatives ZK 93423 (6-benzyloxy-4 methoxymethyl-beta-carboline-3-carboxylic acid ethyl ester) and ZK 91296 (5 benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylic acid ethyl ester) were compared with those of lorazepam and suriclone in squirrel monkeys. Two groups of monkeys were trained to respond under a fixed-interval schedule of food presentation. In one group, responding was suppressed (punished) by superimposing a fixed-ratio schedule of response-produced electric shock. Dose-effect curves were determined for all drugs by administering single doses i.m. 15 min before the start of the fixed-interval schedule. Low and intermediate doses of ZK 93423 (0.03-0.3 mg/kg), ZK 91296 (0.3-10.0 mg/kg), lorazepam (0.03-0.3 mg/kg) and suriclone (0.003-0.03 mg/kg) produced dose-related increases in the rates of both suppressed and nonsuppressed responding. The increases in response rates normally produced by maximally effective doses of ZK 93423, ZK 91296, lorazepam or suriclone were eliminated when the drugs were given in combination with the benzodiazepine antagonist Ro 15-1788. Although many beta-carboline derivatives have been found to act as "inverse agonists" at benzodiazepine recognition sites, the present results show that ZK 93423 and ZK 91296 have clear benzodiazepine like (agonist) effects on schedule-controlled behavior in squirrel monkeys. PMID- 2879906 TI - Specialization in beta-1 and beta-2 adrenoceptor distribution in veins of the rabbit face: relationship to myogenic tone and sympathetic nerve innervation. AB - Studies were performed on several superficial veins from the rabbit face to examine the relationship between beta adrenoceptor subtype distribution, intrinsic myogenic tone and sympathetic nerve innervation. Experiments using selective beta adrenoceptor agonists and antagonists indicate that the dorsal nasal and angularis oculi veins possess a homogeneous population of beta-2 adrenoceptors. Sympathetic nerve stimulation in these segments results only in contraction mediated through postjunctional alpha adrenoceptors. These segments are devoid of intrinsic myogenic tone. In the facial vein, of which both veins are tributaries, both beta-1 and beta-2 adrenoceptors are found. Studies with the beta-1 adrenoceptor antagonist, betaxolol, and beta-2 adrenoceptor antagonist, ICI 118,551, indicate that the prominent relaxation observed in this tissue to sympathetic nerve stimulation is mediated through postjunctional beta-1 adrenoceptors. At physiological temperatures, the facial vein possesses a marked intrinsic myogenic tone that is inhibited by this beta-1 adrenoceptor-mediated sympathetic activity. Considering the anatomical relationship between these vessels and the unique association between beta adrenoceptor subtype, intrinsic myogenic tone and sympathetic innervation, it is possible that facial blood redistribution in the rabbit can be markedly affected by sympathetic nerve stimulation. Such a process could have an important role in cranial thermoregulation. PMID- 2879908 TI - Phencyclidine selectively inhibits N-methyl-D-aspartate-induced hippocampal [3H]norepinephrine release. AB - We have reported previously that phencyclidine (PCP) antagonizes N-methyl-D aspartate (NMDA)-induced release of dopamine and acetylcholine from slices of rat striatum and nucleus accumbens. In the present experiments, we examined the effect of PCP on NMDA and kainic acid (KA)-induced release of [3H]norepinephrine (NE) from superfused rat hippocampal slices. NMDA and KA stimulated the efflux of NE with EC50 values of 192 and 245 microM, respectively. The presence of 1.2 mM MgCl2 in the buffer abolished NMDA-induced release but had little effect on KA induced release. PCP inhibited the release of [3H]NE induced by 100 microM NMDA with an IC50 of 46 nM, but had no effect on the release of NE stimulated by 300 microM KA. 2-Aminophosphonovalerate antagonized NMDA-induced release, producing a parallel shift to the right in the concentration-response curve. However, PCP shifted the concentration-response curve to the right in a nonparallel fashion. Drugs with PCP-like properties, such as dexoxadrol and cyclazocine, inhibited NMDA-induced release, whereas related drugs such as levoxadrol, ethylketocyclazocine and morphine, which are not PCP-like, had no effect. These data suggest that PCP is a potent, selective, noncompetitive inhibitor of amino acid-induced [3H]NE release and that this action of PCP is mediated through the PCP/sigma receptor. PMID- 2879909 TI - Receptors for 5-hydroxytryptamine in rabbit blood vessels: activation of alpha adrenoceptors in rabbit thoracic aorta. AB - Experiments were carried out to identify the receptors mediating the contraction of the rabbit thoracic aorta to 5-hydroxytryptamine (5-HT). Isolated aortic rings were mounted in tissue baths for the measurement of isometric contraction and 5 HT dose-response curves were obtained in the presence and absence of receptor antagonists. Prazosin, 1 X 10(-7) M, or 30-min pretreatment with 1 X 10(-5) M benextramine had no effect on the contractile response of aorta to 5-HT up to 1 X 10(-5) M, whereas 2 brom-D-lysergic acid diethylamide, 1 X 10(-7) M, shifted the 5-HT dose-response curve far to the right. Alpha receptor blockade with either prazosin or benextramine in the presence of 2 brom-D-lysergic acid diethylamide produced a greater blockade than that caused by 2 brom-D-lysergic acid diethylamide alone. When 5-HT dose-response curves were extended to 1 X 10(-3) M, three phases were identified. The first, a dose-related contraction, was mediated exclusively by serotonergic receptors. The second, a relaxation to approximately 40% of maximum, occurred at 1 X 10(-5) M and appeared to result from the rapid development of tachyphylaxis. The third phase was a dose-related contraction to concentrations of 5-HT above 1 X 10(-5) M and was inhibited by either prazosin or pretreatment with benextramine. Similar results were obtained in aortic rings from reserpine-pretreated rabbits. It is concluded that the contractile response to concentrations of 5-HT below 1 X 10(-5) M is mediated exclusively by serotonergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879910 TI - Phorbol ester inhibits bradykinin-stimulated inositol trisphosphate formation and calcium mobilization in neuroblastoma x glioma hybrid NG108-15 cells. AB - In neuroblastoma x glioma hybrid NG108-15 cells, bradykinin (BK) receptor stimulation leads to phosphoinositide hydrolysis, formation of inositol phosphates and mobilization of intracellular calcium. Treatment of the cells with 12-O-tetradecanoyl phorbol 13-acetate (TPA) suppressed the spike phase of increases in intracellular calcium concentration. In radioligand binding studies, TPA treatment did not interfere with [3H]BK specific binding to intact cells or to cell membranes. The ability of guanyl-5'-yl-imidodiphosphate to promote the conversion of the high affinity sites of the BK receptors into a low affinity sites was unaffected by TPA. TPA treatment showed the dose-dependent, noncompetitive inhibition of BK-stimulated formation of inositol trisphosphate. In the membrane preparations from TPA-treated cells, guanosine 5'-(3-O thio)triphosphate-stimulated inositol trisphosphate formation was inhibited by 50%. These data indicate that TPA exerts its inhibitory action on BK responses at the sites of guanine nucleotide-binding protein or phospholipase C or both. PMID- 2879912 TI - Synthesis of 2-(4-substituted-1-piperazinyl)benzimidazoles as H1-antihistaminic agents. AB - A series of 2-(4-substituted-1-(homo)piperazinyl)benzimidazoles was prepared and tested for H1-antihistaminic activity in vitro and in vivo. Most of the compounds showed antihistaminic activity and some of the 1-[2-(substituted-oxy)ethyl] derivatives exhibited potent activity. In a structure-activity comparison it was found that the oxygen atom in the 2-(substituted-oxy)ethyl group at the 1 position of the benzimidazole nucleus played an important role for potent antihistaminic activity, especially in vivo. One of the most potent compounds, 1 (2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole (69), was 39 times more potent than chlorpheniramine maleate in H1-antihistaminic activity in vivo and was selected for clinical evaluation. The structure of compound 69 is of interest because it provides only a single aromatic unit linked through a chain to a basic nitrogen, while most H1-antihistaminic agents have structures that comprise a double-aromatic unit linked through a chain to a basic tertiary amino group. PMID- 2879911 TI - Neuropeptide Y and somatostatin immunoreactive perikarya in preaortic ganglia projecting to the rat ovary. AB - Postganglionic perikarya in preaortic ganglia projecting to the ovary of the rat were identified utilizing the retrograde fluorescent tracer, true blue. Ovarian perikarya were subsequently examined for neuropeptide Y and somatostatin immunoreactivity. True blue-labelled ovarian postganglionic perikarya were distributed in the coeliac ganglion and in smaller ganglia located at the origins of the renal and ovarian arteries. In the coeliac ganglia, 74.4 +/- 18.8% of true blue-labelled ovarian perikarya were immunoreactive to neuropeptide Y while 37.4 +/- 9.6% were immunoreactive to somatostatin. In the inferior smaller ganglia, 72.2 +/- 18.7% and 2.2 +/- 2.2% of the true blue-labelled ovarian perikarya were immunoreactive to neuropeptide Y and somatostatin respectively. It is suggested that neuropeptide Y and somatostatin participate in the modulation of ovarian function. PMID- 2879913 TI - Two stereoisomeric imidazoline derivatives: synthesis and optical and alpha 2 adrenoceptor activities. AB - Two eight-step pathways for synthesizing the stereoisomeric compounds (-)-2-[1 (2,6-dichlorophenoxy)ethyl]-2-imidazoline hydrochloride ("levlofexidine" hydrochloride; (-)-lofexidine hydrochloride) and (+)-2-[1-(2,6 dichlorophenoxy)ethyl]-2-imidazoline hydrochloride ("dexlofexidine" hydrochloride; (+)-lofexidine hydrochloride) and the optical resolution of (+/-) lofexidine are described. (-)-Lofexidine, a stereoselective alpha 2-adrenoceptor agonist, due to its center of asymmetry, is demonstrated to be a potent drug for the treatment of hypertension (doses 0.561 microgram/kg) and to have the highest affinity and a concentration dependency for alpha 2-adrenoceptors in direct binding studies (0.36 nmol/L). (+)-Lofexidine is 10 times less potent. PMID- 2879914 TI - Peptides as receptor selectivity modulators of opiate pharmacophores. AB - In an effort to investigate whether "address" segments of endogenous opioid peptides, which are responsible for modulating receptor selectivity, also could modulate the selectivity of opioid alkaloid pharmacophores, we have synthesized analogues of leucine-enkephalin and dynorphin in which the N-terminal dipeptide "message" sequence has been replaced by oxymorphone or naltrexone. A hydrazone group was employed as a linkage between the alkaloids and peptides. The binding data for mu, kappa, and delta receptors indicate that peptide portions of the analogues can modulate the receptor selectivity of the attached alkaloid pharmacophores. The selectivity for different opioid receptor types depends on a balance between the affinities of the message and address components. In cases where these components have comparable receptor affinities, the address can significantly shift selectivity by increasing affinity to one receptor type while reducing affinity to other types. When the message component has high affinity for a particular receptor type, the modulatory role of the address is expressed mainly by reducing the affinity of the ligand for other opioid receptor types. PMID- 2879915 TI - 1-(2-pyridinyl)piperazine derivatives with antianaphylactic, antibronchospastic, and mast cell stabilizing activities. AB - New 1-(2-pyridinyl)piperazine derivatives were synthesized and tested as inhibitors of the reaginic passive cutaneous anaphylaxis in the rat (PCA), of the histamine-induced bronchospasm in the guinea pig, and of the rat mesenteric mast cell degranulation induced by compound 48/80. On the basis of test results, a series of N-(substituted phenyl)-omega-[4-(2-pyridinyl)-1-piperazinyl]alkanamides was prepared. The nature of substituents at the anilide ring strongly influenced mast cell stabilizing activity, whereas it was less determining in the case of the other two tests. No clear correlation between the most common physicochemical parameters (pi, sigma, Vw volume) of substituents and activity could be detected. With regard to the position of substituents at the anilide ring, the rank order of potency, in the PCA and bronchoconstriction tests, was para greater than meta greater than ortho. Introduction of substituents in the 1-(2 pyridinyl)piperazinyl moiety of the N-(substituted phenyl)propanamide derivatives hardly affected activity, or the effect was deleterious. Some of the new compounds exhibited a simultaneous remarkable activity in all the three assays employed. PMID- 2879916 TI - Conformationally defined adrenergic agents. 4. 1-(aminomethyl)phthalans: synthesis and pharmacological consequences of the phthalan ring oxygen atom. AB - The synthesis of a series of 1-(aminomethyl)phthalans 1b is reported. The radioligand binding to alpha 1- and alpha 2-receptors and the in vitro pharmacology in alpha 1 (rabbit aorta) and alpha 2 (phenoxybenzamine-pretreated dog saphenous vein) tissues were determined and were compared to the activity of the corresponding 1-(aminomethyl)indans. The activity of this series of phthalans was found to be consistent with the electrostatic repulsion hypothesis that was used to design the parent indan (ERBCOP) compounds. The effect of the phthalan ring oxygenation was to somewhat improve alpha 1-receptor potency relative to the 6-ERBCOP indans without having a general effect on the alpha 2-receptor potency. We conclude from the overall pattern of activity that while the norepinephrine type beta-hydroxyl group may be beneficial for binding to the alpha 1 adrenoceptor, it is not required for strong binding to or full stimulation of the alpha 2-adrenergic receptor, provided that the conformational mobility associated with the phenylethylamine is restricted and maintained in a favorable conformation for receptor interaction. PMID- 2879917 TI - N-(heterocyclic alkyl)pyrido[2,1-b]quinazoline-8-carboxamides as orally active antiallergy agents. AB - A series of N-(heterocyclic alkyl)pyrido[2,1-b]quinazoline-8-carboxamides were evaluated for their ability to antagonize slow-reacting substance of anaphylaxis (SRS-A) induced contractions of guinea pig ilea and to inhibit thromboxane synthase in vitro. The results indicated that those pyrido[2,1-b]quinazoline-8 carboxamides bearing a branched-chain alkyl moiety in the 2-position and a four to six atom linear chain between a 3- or 4-substituted pyridine or a 1 substituted imidazole ring and the carboxamide nitrogen atom showed the best combination of potencies in the two assays. Several of these compounds were found to be orally active inhibitors of LTE4-induced bronchoconstriction in the guinea pig and LTE4-induced skin wheal formation in the rat. One of the most potent analogues, 2-(1-methyl-ethyl)-N-(1H-imidazol-1-ylbutyl)-11-oxo-11H-pyrido [2,1 b]quinazoline-8-carboxamide (36), was selected for extensive pharmacological investigation. It was found that this compound was not a specific inhibitor of LTE4-induced symptomatology, but exhibited more general activity by inhibiting bronchospasm in guinea pigs induced by LTC4, LTD4, PAF, and histamine and skin wheal formation in rats and guinea pigs induced by LTC4, LTD4, and PAF. In addition, 36 was orally active in the passive cutaneous anaphylaxis assay, suggesting that it also exhibits mediator release inhibitory activity. On the basis of the overall pharmacological profile of 36 and its closely related analogues, it was concluded that these compounds may be useful for the treatment of asthma. PMID- 2879918 TI - Synthetic analogues of tetrahydrobiopterin with cofactor activity for aromatic amino acid hydroxylases. AB - Tetrahydrobiopterin (THB) analogues with 6-alkoxymethyl substituents, 3a-j, where the substituents were straight- and branched-chain alkyl ranging from methyl to octyl, have been synthesized by the Taylor method from pyrazine ortho amino nitriles by guanidine cyclization, hydrolysis in aqueous NaOH, and catalytic hydrogenation over Pt in trifluoroacetic acid (TFA). The best of these compounds, 3b, is an excellent cofactor for phenylalanine hydroxylase, tyrosine hydroxylase (V = 154% of THB), and tryptophan hydroxylase, does not destablize the binding of substrate (Kmtyr = 23 microM), and is recycled by dihydropteridine reductase (V = 419% of THB). The compounds are being evaluated as cofactor replacements in biopterin-deficiency diseases. PMID- 2879919 TI - 2,4-diamino-6,7-dimethoxyquinazolines. 1. 2-[4-(1,4-benzodioxan-2 ylcarbonyl)piperazin-1-yl] derivatives as alpha 1-adrenoceptor antagonists and antihypertensive agents. AB - A series of 4-amino-2-[4-(1,4-benzodioxan-2-ylcarbonyl)piperazin-1 -yl]-6, 7 dimethoxyquinazoline derivatives was synthesized for evaluation as alpha antagonists and antihypertensive agents. Most compounds displayed high (nM) binding affinity for alpha 1-adrenoceptors with no significant activity at alpha 2-sites. Selective antagonism of the alpha 1-mediated vasoconstrictor effects of norepinephrine is also characteristic of the series. Structure-activity relationships for alpha 1-adrenoceptor affinity are presented, and structural similarity between the 2,4-diamino-6,7-dimethoxyquinazoline nucleus and norepinephrine is established. An alpha 1-receptor model is presented in which charge-reinforced hydrogen bonding is important for binding of both antagonist and agonist molecules. Antihypertensive activity was evaluated after oral administration (5 mg/kg) to spontaneously hypertensive rats, and several compounds displayed similar efficacy to prazosin when assessed after 6 h. On the basis of alpha 1-adrenoceptor affinity/selectivity in vitro and duration of antihypertensive action in vivo, compound 1 (doxazosin) was selected for further evaluation and is currently progressing through phase III clinical trials. PMID- 2879920 TI - 5-fluoro- and 8-fluorotrimetoquinol: selective beta 2-adrenoceptor agonists. AB - The 5-fluoro and 8-fluoro analogues of trimetoquinol, TMQ, have been synthesized and evaluated for beta 2- and beta 1-adrenoceptor activity in guinea pig trachea and atria, respectively. The fluoro analogues of TMQ maintained potent beta 2 adrenoceptor agonist activity but had reduced beta 1-adrenoceptor agonist activity. The changes in beta 1-activity of these compounds were correlated to differences in phenolic pKa's. The beta 1- and beta 2-adrenoceptor actions of 2 and 3 were blocked in a competitive manner by propranolol. The enhanced beta 2/beta 1 selectivity for the analogues was found to be 8-fluoro analogue 3 greater than 5-fluoro analogue 2 greater than trimetoquinol (1). PMID- 2879921 TI - Paternal inheritance of translocation chromosomes in a t(X;21) patient with X linked muscular dystrophy. AB - A number of DNA probes from the short arm of the X chromosome have been used to study the inheritance of the translocation chromosomes in a girl with an X; autosome translocation and muscular dystrophy. The two translocation chromosomes were found to be derived from the father's single normal X chromosome, ruling out maternal inheritance of a pre-existent mutation and enhancing the concept that the de novo translocation is responsible for the dystrophic phenotype. PMID- 2879922 TI - Duchenne muscular dystrophy in one of monozygotic twin girls. AB - Monozygotic twin girls are reported, one of whom has the typical clinical features of Duchenne muscular dystrophy despite a normal female karyotype. Although certain features of the biopsy were atypical, the clinical diagnosis was supported by persistent markedly raised blood creatine kinase levels and findings typical of DMD on electromyography and magnetic resonance spectroscopy. Analysis of an X linked DNA polymorphism in 16 independent somatic cell hybrids made between cells derived from each girl and a mouse line suggest that in one twin only the maternal X chromosome is active, whereas in the other the active X was paternally derived. More data are needed to exclude sampling error. These preliminary experimental results support the hypothesis that both girls are heterozygous for Duchenne muscular dystrophy. X inactivation, by chance, resulted in two contrasting cell masses with different active X chromosomes. This segregation was followed by, and may even have resulted in, twinning into a female pair, one normal and one with the full clinical features of the disease. PMID- 2879923 TI - Molecular deletion analysis in Duchenne muscular dystrophy. AB - Study of 165 unrelated patients with X linked muscular dystrophy (117 with Duchenne and 48 with Becker dystrophy) has shown nine Duchenne cases (8% of the total) where a molecular deletion was detected using probes pERT87 or XJ1.1. No cytogenetic abnormalities were detectable in this unselected series of patients and no clear clinical or other differences were found between deletion and non deletion cases. No deletions were found in the 48 Becker patients. Analysis of the families allowed unequivocal identification carrier status in females hemizygous for the deleted allele. Since some of the deletions were detected with only one of the two probes, it is important that both pERT87 and XJ1.1 are used when studying patients for molecular deletions. PMID- 2879924 TI - Localisation of Xp21 meiotic exchange points in Duchenne muscular dystrophy families. AB - The inheritance of Duchenne muscular dystrophy in 25 families was studied with 13 X chromosome specific cloned DNA fragments from 10 loci in and surrounding Xp21. When multiple probes were informative, the meiotic exchange points for each meiosis were located in individual families. Neither genetic nor physical evidence indicates an unusually high recombination rate across Xp21 in these 25 families. PMID- 2879925 TI - Linkage studies in Duchenne and Becker muscular dystrophies. AB - We have studied the inheritance of four cloned DNA sequences which recognise restriction fragment length polymorphisms on the short arm of the X chromosome in families with Becker and Duchenne muscular dystrophy. We have confirmed linkage of two probe loci to the disease loci and have combined our results with those previously published to give a maximum lod score of 11.642 at a recombination fraction of 0.15 for DXS41 (probe 99.6), and a maximum lod of 15.84 at a recombination fraction of 0.15 for DXS84 (probe 754). Linkage of these diseases to the loci defined by the pERT87 probes and probe pXJ1.1 has also been studied, giving maximum lod scores of 8.634 and 5.118 at recombination fractions of 0.02 and 0.00 respectively. The information obtained using these polymorphic DNA markers, combined with pedigree and CK data, can be used to give more accurate genetic counselling to women at risk in Becker and Duchenne families. PMID- 2879927 TI - Prenatal diagnosis of Duchenne muscular dystrophy by DNA analysis. AB - Linkage studies have been carried out in 20 families segregating for Duchenne muscular dystrophy and eight prenatal diagnoses performed, including six first trimester diagnoses and one twin pregnancy. The results of the restriction fragment length polymorphism (RFLP) analysis suggest that not all the possible RFLPs need to be used and a strategy for carrier detection studies is proposed. PMID- 2879926 TI - Linkage analysis of polymorphisms within the DNA fragment XJ cloned from the breakpoint of an X;21 translocation associated with X linked muscular dystrophy. AB - Cloning of a DNA segment including the translocation breakpoint in a female with an X;21 translocation and X linked muscular dystrophy has led to identification of three subclones which detect polymorphic markers. The alleles of these markers, XJ1 X 1, XJ1 X 2, and XJ2 X 2, are in strong linkage disequilibrium. Linkage analysis in 31 families with Duchenne or Becker muscular dystrophy has shown recombination within the XJ segment in one case, and recombination of DMD with both the XJ segment and the pERT87 segment in a second, but has revealed no recombination between the XJ and pERT87 segments. The XJ markers increase the proportion of DMD and BMD families that are informative for carrier detection and prenatal diagnosis, but in view of the risk of recombination they must be used with caution. The site(s) of the DMD mutation(s) relative to the XJ and pERT87 markers, and the detailed molecular structure of the DMD region, remain to be determined. PMID- 2879928 TI - Carrier detection and prenatal diagnosis in X linked muscular dystrophy using restriction fragment length polymorphisms. AB - With the aim of offering carrier detection, genetic counselling, and prenatal diagnosis to as many families with Duchenne (DMD) and Becker (BMD) muscular dystrophy as possible, we used available DNA probes to determine the usefulness of the RFLP approach. We report in detail the risks calculated using Bayesian theory and combining pedigree and creatine kinase (CK) data with information derived from the RFLP studies. To date we have analysed members of 28 DMD families (10 familial, 18 sporadic) and six BMD families (four familial, two sporadic) with the closely linked pERT probes 87-1, 87-8, and 87-15 (DXS164). In addition, key members of all families were analysed with probes D2 (DXS43), C7 (DXS28), 754 (DXS84), and L1 X 28 (DXS7). Of the 97 females at risk of being carriers (not including 26 obligate carriers), the RFLP results were compatible with carriership in 22 and not in 51. In 24 females (including 17 mothers of sporadic cases), no information regarding carriership was derived from the RFLP studies. There was no disagreement between pedigree information, clearly raised CK values, and DNA studies. Of 52 obligate or possible carriers under the age of 45, prenatal diagnosis is possible in 49. Prenatal diagnostic RFLP studies have so far been done in three women. In one sporadic DMD family and one BMD family with three affected males the probands showed a deletion involving the three pERT87 subclones used. Experience derived from these families indicates that in our society genetic counselling in X linked muscular dystrophy is received with approval or even enthusiasm in spite of the 5% error estimate that we have quoted for pERT87 derived results. PMID- 2879929 TI - DNA probe analysis for carrier detection and prenatal diagnosis of Duchenne muscular dystrophy: a standard diagnostic procedure. AB - Thirteen marker loci localised on the short arm of the X chromosome are available for use in genetic studies for Duchenne muscular dystrophy (DMD). This large number of probes detecting about 20 RFLPs encouraged us to set up a standard procedure using a sequence of selected probes and restriction enzymes for the diagnosis of DMD families. The application of DNA probe analysis for carrier detection and prenatal diagnosis, involving 61 pedigrees of both familial and isolated cases, has yielded the following results. Carrier detection using flanking markers was possible in more than 75% of the cases (104 out of 136 females) with a reliability of better than 98%. Prenatal diagnosis was possible in 95% of the cases (65 out of 68 proven carriers or women at risk). Twenty-three prenatal diagnoses were performed on male fetuses; 13 appeared to have a low risk for DMD (less than 1%) and thus the pregnancies continued. Seven have since come to term and the male infants have normal CK levels. The genetic distances of the loci relative to the DMD locus and their order on the short arm of the X chromosome were deduced from our total DMD family material and are not significantly different from those reported earlier. For 754 (DXS84) we found a genetic distance of 5 cM with a lod score of +12.4 and 95% confidence limits between 2 and 12 cM. Similar data were obtained for pERT87 (DXS164), suggesting that in our family material both loci are tightly linked. Multiply informative recombination showed that both 754 and pERT87 map proximal to the DMD mutations in the cases studied. The high frequency of DMD mutations and its relation to the observed instability in this part of the genome will be discussed. Unequal crossing over is proposed as one of the mechanisms contributing to the high mutation frequency. PMID- 2879930 TI - A register based system for gene tracking in Duchenne muscular dystrophy. AB - A total of 102 families with Duchenne muscular dystrophy has been studied with linked DNA polymorphisms as an aid to estimating carrier risks for female relatives. Early work using probes RC8, L1.28, and pXUT23 gave very little clinically useful information because of the high recombination rates between these probes and Duchenne muscular dystrophy and the low proportion of women who were heterozygous. Clinically useful results were obtained using probes 99-6, 754, and particularly pERT87. Examples are given of deductions which can be made using these probes. The importance of a genetic register is stressed as a tool for long term contact with the families and other professionals. PMID- 2879931 TI - Emery-Dreifuss muscular dystrophy: localisation to Xq27.3----qter confirmed by linkage to the factor VIII gene. AB - Two families with Emery-Dreifuss muscular dystrophy (EMD) have been studied with DNA markers mapping to Xq27.3----qter. No recombination was observed in 11 phase known meioses informative for the factor VIII gene (F8C) and eight phase known meioses informative for DXS15 (DX13), giving maximum lod scores of 3.50 and 2.50 respectively at a recombination fraction of zero. DXS52 (St14) showed one recombinant in 12 phase known meioses giving a maximum lod score of 2.62 at a recombination fraction of 0.07. These results map EMD to the distal end of the long arm of the X chromosome and are an important step in the development of tests for carrier detection and prenatal diagnosis. PMID- 2879932 TI - Linkage analysis using multiple Xq DNA polymorphisms in normal families, families with the fragile X syndrome, and other families with X linked conditions. AB - Multipoint linkage analysis was undertaken with eight Xq cloned DNA sequences which identify one or more restriction fragment length polymorphisms in 26 families. These families comprise seven phase known normal families with three or more males in the third generation, seven families segregating for haemophilia B, one large family with dyskeratosis congenita, and 11 families with the fragile X syndrome. Phase known meioses informative for three or more loci supported the order centromere--DXYS1--DXS107--DXS102, DXS51--F9--FRAXA--DXS15, DXS52, F8- Xqter in each group of families studied. One of the normal families was segregating for protan colour blindness and showed a phase known recombination which would support the order centromere--F9--DXS52--CBP--Xqter. With the exception of DXYS1, all of these sequences have been localised to Xq27----qter by in situ hybridisation or hybridisation to Xq fragment panels, and on this basis should lie within 20 cM of one another. No recombination was observed between the sequences localised to Xq28, namely DXS52, F8, and DXS15 (between DXS15 and DXS52 Z = 12.25 at theta = 0 with confidence limits of 0 to 5 cM). However, an excess of recombination was apparent in the region of FRAXA with maximal lod scores as follows: F9 versus FRAXA (Z = 2.05, theta = 0.19), DXS52 versus FRAXA (Z = 1.85, theta = 0.26), and DXS15 versus FRAXA (Z = 1.33, theta = 0.27). No consistent differences were observed in the frequency of recombination when families with the fragile X syndrome were compared with normal families or families segregating for other X linked conditions. These results are compared with other published work and support the conclusion that although measurable linkage exists between these flanking markers and FRAXA, the intervals as measured by the frequency of meiotic recombination will seriously limit their clinical usefulness. PMID- 2879934 TI - DNA polymorphisms of the human alpha 1 antitrypsin gene in normal subjects and in patients with pulmonary emphysema. AB - Alpha 1 antitrypsin deficiency predisposes subjects to developing pulmonary emphysema and childhood liver cirrhosis. We have studied restriction fragment length polymorphisms (RFLPs) of the alpha 1 antitrypsin gene in a normal population and a group of patients with pulmonary emphysema. We have identified five RFLPs with eight restriction enzymes. The most frequent polymorphisms have been detected with the enzymes MspI, PstI, and TaqI at frequencies of 46.8%, 6.4%, and 5.0% respectively in the group of normal subjects. PMID- 2879933 TI - High resolution gene mapping of the human alpha globin locus. AB - A combination of polymorphic DNA markers, cytogenetic analysis, and in situ hybridisation has been used for the high resolution assignment of the human alpha globin gene cluster on chromosome 16. Multiallelic DNA probes from within the alpha globin cluster were used to determine the number of copies of this locus in three cell lines containing trisomies of the short arm of chromosome 16 and one with a familial inversion, inv(16). The breakpoints in these rearrangements flank the alpha globin locus and locate a shortest region of overlap to 16p13.1. A meiotic crossover was also localised to this band. In situ hybridisation of biotinylated DNA probes to normal and inverted chromosomes 16 [inv(16)(p13.1;q22)] showed hybridisation sites at opposite ends of the chromosomes, consistent with this regional localisation. PMID- 2879936 TI - Structure of F-pili: reassessment of the symmetry. AB - Reassessment of the X-ray fibre diffraction patterns of F-pili using a more accurate subunit molecular weight suggests that subunits in F-pili are related by a fivefold rotation axis around the pilus axis. The identity of this fivefold symmetry with the fivefold rotation axis that relates the subunits in fd bacteriophage supports a simple model for tip-to-tip adsorption of bacteriophage to pili. PMID- 2879935 TI - Prenatal diagnosis of alpha 1 antitrypsin deficiency and estimates of fetal risk for disease. AB - Alpha 1 antitrypsin deficiency is one of the most common metabolic disorders, frequently associated with obstructive lung disease and occasionally with childhood liver cirrhosis. Prenatal diagnosis of this deficiency has been accomplished using a DNA polymorphism detected by the restriction enzyme AvaII. A unique haplotype of DNA fragments is observed in deficient (PI type ZZ) subjects. Diagnosis is therefore possible directly from fetal tissue, unlike other prenatal diagnoses using linkage of a DNA polymorphism within a specific family. This approach must be modified for rare deficiency alleles of alpha 1 antitrypsin (PI* Mmalton, PI* Mdurate, and PI*QO or null). Knowledge of risk of severe disease in the fetus is important for the application of prenatal diagnosis. From the limited data available to date, the risk for a given PI ZZ fetus to develop severe liver disease has been estimated at 13% where a previous PI ZZ sib had no liver disease or liver disease which resolved during early childhood, and a risk of 40% where a previous PI ZZ sib had developed severe liver disease. PMID- 2879937 TI - Alpha adrenoceptors--an overview. AB - The realisation that transmitter noradrenaline modulated its own release through a pre-junctionally located alpha-adrenoceptor operated control mechanism explained several paradoxical phenomena and raised exciting therapeutic possibilities. Characterisation of the pre- and post-junctional effects of agonists and antagonists led to the conclusion that pre- and post-junctional alpha-adrenoceptors differed in receptor structure and alpha-adrenoceptors were sub-divided into alpha 1- and alpha 2-adrenoceptors. It was subsequently shown that in addition to the differences in receptor structure the biochemical mechanisms of signal transduction were entirely different in the case of each sub type of adrenoceptor. It has been hypothesised that automodulation of transmitter noradrenaline release occurs between neighbouring varicosities in densely innervated organs and as a consequence ensures that homogeneity in tissue noradrenaline concentration is achieved. In the heart the loss of such automodulation could result in inhomogeneity in transmitter concentration and under certain circumstances favour re-entry phenomena and arrhythmogenesis. There is now a large body of evidence documenting the presence of post-junctional alpha 1-adrenoceptors in the mammalian heart. Recent experimental work strongly supports the concept that enhanced alpha 1-adrenoceptor responsiveness plays a primary pathophysiological role in the genesis of malignant dysrhythmias induced by catecholamines during myocardial ischaemia and reperfusion. Alpha 1 adrenoceptor antagonists have been shown to be effective in restoring sinus rhythm after such arrhythmias have been experimentally induced. It is anticipated that alpha 1-adrenoceptor antagonists possessing potent antiarrhythmic activity and causing minimal changes in heart rate and arterial blood pressure, will become available and be employed to ascertain whether or not the animal results translate to man. PMID- 2879938 TI - Alpha-adrenergic mechanisms in the pathophysiology of left ventricular heart failure--an analysis of their role in systolic and diastolic dysfunction. AB - Alpha-adrenoceptor (alpha-AR) mechanisms may contribute to systolic and diastolic dysfunction of the left ventricle. Centrally acting alpha 2-AR agonist drugs, including methyldopa, clonidine, and guanabenz, activate brainstem alpha 2-AR and this activation results in a decrease in overall sympathetic tone and an increase in parasympathetic tone. Peripherally acting alpha 1-AR antagonists, such as prazosin, inhibit the actions of catecholamines at post-synaptic receptor sites. Heart failure is characterized by hyperactivity of sympathetic pathways and parasympathetic withdrawal. In this situation, alpha 2-agonists reduce sympathetic activity and improve hemodynamic parameters of cardiac function; both acute and chronic administration of alpha 2-AR have been demonstrated to reduce serum catecholamine levels, heart rate, and arterial blood pressure, and to improve exercise performance. Diastolic dysfunction of the left ventricle is characterized by a marked decrease in ventricular compliance, often a result of hypertension and left ventricular hypertrophy; the end result is an increase in left ventricular filling pressure and pulmonary venous pressure. Treatment with alpha 2-AR, by decreasing sympathetic tone and blood pressure, and alpha 1-AR antagonists, by reducing blood pressure and by directly inhibiting the actions of catecholamines at alpha 1-AR, may produce a reduction in the degree of ventricular hypertrophy and improve diastolic performance of the left ventricle. Thus, therapeutic intervention in heart failure with either alpha 2-AR agonists or alpha 1-AR antagonists may favorably modulate these alterations in sympathetic tone and improve ventricular function. PMID- 2879939 TI - Alpha adrenoceptors and arrhythmias. PMID- 2879940 TI - Alpha adrenergic receptor mechanism: biochemical events. AB - Immediate post-receptor events following alpha-adrenoceptor stimulation in cardiac ventricular muscle are still largely unknown. Since membrane redox systems appear to be present in cell plasma membranes and may be involved in trans-sarcolemma electron efflux, the possibility that Ca2+ inflow was controlled by electron efflux was explored. Electron efflux was measured by monitoring the rate of reduction of extracellular ferricyanide (a non-permeant anion) and compared with changes in contractility of the perfused heart as an indirect assessment of altered cytoplasmic Ca2+ concentration. Alpha-agonists significantly increased the rate of ferricyanide reduction by approx. 42%. Activation was dose- and time-dependent and closely accompanied changes in contractility either when the alpha-agonist was added or removed. Perfusion of the heart with sufficient Ca2+ chelating agent to prevent beating, did not affect the rate of ferricyanide reduction, but amplified the stimulatory effect of methoxamine on this rate. Kinetic assessment indicated that alpha-agonists led to an increase in the number of electron efflux sites in the ventricular sarcolemma. Neither diacyl glycerol nor the Ca2+ ionophone A23187 or a combination of the two had any effect on electron efflux rates. It is proposed that alpha-adrenoceptor stimulation promotes Ca2+ entry into the heart cell by directly activating the rate of electron efflux. An accompanying outward release of protons from localized regions of the sarcolemma (Ca2+ channels?) may then facilitate a 1-for 2 inward movement of Ca2+. PMID- 2879941 TI - Medical services provided to 2,394 patients at methadone programs in three states. AB - The type and amount of medical services provided to 2,394 patients in methadone maintenance programs in three states was studied. Data were obtained from on-site confidential interviews with the entire treatment staff at seven programs. It was found that there were marked differences in the number and type of medical staff. Thus, there was ten times more coverage by physicians at some programs than others. In general, there were notable differences in the treatment staff available. Comparable variations among the programs were found with respect to the actual provision of medical services. Thus, the number of patients seen by the medical staff on a weekly basis varied from a high of 185 patients to a low of 36 patients. Similarly, the proportion of each program's patients receiving medical treatment per week varied from 53 to 14 percent. Reasons for those variations in medical services are considered. PMID- 2879943 TI - The presence of intersexuality in patients with advanced hypospadias and undescended gonads. AB - We studied 20 patients with advanced degrees of hypospadias and undescended testes for the presence of an intersex disorder. A comprehensive clinical, cytogenetic, endocrinological and surgical evaluation was performed. All patients were found to have an intersex disorder, including 10 with male pseudohermaphroditism and 10 with a gonadal/genetic intersex disorder. In the latter group 4 patients had mixed gonadal dysgenesis, 3 had dysgenetic male pseudohermaphroditism, 1 had the 46XX male syndrome, 1 had true hermaphroditism and 1 had Klinefelter's syndrome. Genetic and gonadal intersex disorders were more frequent in patients with a unilateral undescended testis and perineal hypospadias. PMID- 2879942 TI - Adenovirus-dependent changes in cell membrane permeability: role of Na+, K+ ATPase. AB - Adenovirus-dependent release of choline phosphate from KB cells at pH 6.0 was partially blocked by ouabain. In K+-containing medium, maximum inhibition of release was obtained by 10(-5) M ouabain and half-maximal inhibition was achieved by about 0.5 X 10(-6)M ouabain. Ouabain did not block either the binding or the uptake of adenovirus by KB cells. Without K+, about 25% of cell-associated choline phosphate was released by adenovirus, whereas with 1 mM K+ about 50% was released. This activation by K+ was blocked by 0.1 mM ouabain. HeLa cells behaved like KB cells, but a mutant of HeLa cells resistant to ouabain (D98-OR) released much lower amounts of choline phosphate in response to human adenovirus type 2 (Ad2). Wild-type D98-OR cells bound nearly the same amount of adenovirus as did normal HeLa cells. Ad2 also increased the activity of Na+,K+-ATPase in KB cells, with maximum activation at 50 micrograms of Ad2 per ml. In D98-OR cells, Ad2 failed to activate Na+,K+-ATPase activity. Ad2-dependent lysis of endocytic vesicles (receptosomes) was assayed by measuring Ad2-dependent enhancement of epidermal growth factor-Pseudomonas exotoxin toxicity. This action of adenovirus was increased when K+ was present in the medium. Under the conditions used, K+ had no effect on the amount of Ad2 or epidermal growth factor taken up by the cells. On the basis of these results, it is suggested that Ad2-dependent cellular efflux of choline phosphate and adenovirus-dependent lysis of receptosomes may require Na+,K+-ATPase activity. PMID- 2879944 TI - Carcinoid tumor of undescended testis. AB - Carcinoid tumor of the testis is rare and its histogenesis is controversial. We report a case of carcinoid tumor in an undescended testis with electron microscopic evidence of neurosecretory granules. PMID- 2879945 TI - Cell-specific ribosomal DNA spacer variability in human urothelial carcinoma cultures. AB - Length variation of a ribosomal DNA "spacer" region in four chromosomally characterized transitional cell carcinoma cultures was analyzed by restriction endonuclease cleavage and Southern blotting. Cell lines with relative karyotypic conservation, such as UM-UC-2 (modal chromosome number 48, four marker chromosomes) demonstrate little change in the genetically regulated pattern of rDNA spacer length polymorphisms (7.6, 6.7 and 6.0 kilobases) which may be found in normal cells. Cell lines with more aberrant karyotypes, such as UM-UC-3 (modal chromosome number 86, 12 marker chromosomes) and UM-UC-4 (modal number 51, ten marker chromosomes) show fewer ribosomal DNA length variants (7.6, 6.7 kilobases for the former, 7.6 kilobases for the latter), consistent with relaxed constraints on the drive for ribosomal gene homogeneity through inter and intrachromosomal exchange. Uncharacterized rDNA length variants of low copy number were observed in cell lines with many marker chromosomes. Analysis of repetitive DNA structure provides an additional criterion for tumor diagnosis and staging, and a characterized series of tumor cell lines may provide a useful system for understanding repetitive DNA evolution. PMID- 2879946 TI - [Endotracheal intubation using vecuronium bromide during pentazocine-diazepam-N2O anesthesia]. PMID- 2879947 TI - [Anesthetic management of a patient with Russell-Silver syndrome]. PMID- 2879948 TI - [Serological study of the antibody to the adult T-cell leukemia-virus-associated antigen in various hematological diseases]. AB - A serological study of antibody to adult T-cell leukemia-virus-associated antigen (anti-HTLV-I antibody) was made in 170 cases of various hematological diseases at Shikoku Cancer Center Hospital. The titer of anti-HTLV-I antibody was determined by indirect immunofluorescence using the MT-2 cell line. Two of two patients with ATL were positive for antibody. In non-Hodgkin's lymphoma, six of 18 cases of T cell phenotype were positive (33%), while two of 29 cases of B-cell phenotype were antibody-positive (7%). Some cases of leukemia and aplastic anemia, who had received multiple blood transfusions, were found to be seropositive. Our results suggest that anti-HTLV-I antibody may be related to non-Hodgkin's lymphoma with T cell phenotype as well as ATL. PMID- 2879949 TI - [Follow-up of lymphocyte morphology and detection of human T-cell leukemia virus type-I (HTLV-I) proviral DNA in HTLV-I carriers]. PMID- 2879950 TI - [Clinical significance of adult T-cell leukemia (ATL)-associated antigens (ATLA), anti-ATLA antibody and adult T-cell leukemia virus (ATLV)/human T-cell leukemia virus type-I (HTLV-I) proviral DNA in ATL, adult T-cell malignant lymphoma (AT ML) and Hodgkin's disease in Kagoshima district]. PMID- 2879951 TI - Effects of a new antihypertensive agent, SGB-1534, on rat platelet aggregation. AB - The present study was designed to examine the antiplatelet activity of SGB-1534, 3-[2-[4-(o-methoxyphenyl)-1-piperazinyl]ethyl]-2,4(1H, 3H)- quinazolinedione monohydrochloride, compared with prazosin, ketanserin and aspirin. The equihypotensive doses of SGB-1534, prazosin and ketanserin were administered orally to rats; and 1 hr later, their effects on collagen-induced platelet aggregation, compared with those of aspirin, were examined under ex vivo conditions. The bleeding time was determined by using the tail transection method. SGB-1534 (10 mg/kg) as well as ketanserin (3 and 10 mg/kg) and aspirin (10 mg/kg) effectively inhibited the platelet aggregation; and in addition, they significantly prolonged bleeding times. Prazosin in doses of 10 and 30 mg/kg did not affect either the aggregation or bleeding times. Whereas 10(-4) M aspirin significantly inhibited the production of malondialdehyde (MDA) in rat platelets, SGB-1534, prazosin and ketanserin even in considerably high concentrations (10( 4) or 10(-3) M) did not affect the MDA production and the cyclic AMP levels in the platelets. In isolated rat femoral arteries, SGB-1534, prazosin and ketanserin antagonized the contractile response to phenylephrine with pA2 values of approximately 10.06, 10.39 and 7.71, respectively. Also, SGB-1534 and ketanserin attenuated the contractile response to 5-hydroxytryptamine (5-HT) with pA2 values of 6.36 and 9.53, respectively, while prazosin had no antagonistic effects on 5-HT-induced contraction. PMID- 2879952 TI - A difference in mode of antagonism between optical isomers of a potent selective alpha 1-adrenoceptor blocker (YM-12617) and norepinephrine in isolated rabbit iris dilator and aorta. AB - Optical isomers of YM-12617, a potent and selective alpha 1-adrenoceptor blocker, were tested on the rabbit iris dilator and aorta. The order of potency was R(-) isomer greater than racemate greater than S(+)-isomer. The R(-)-isomer and racemate behaved as an essentially irreversible antagonist to norepinephrine in the iris dilator where the efficacy of norepinephrine was small, although the S(+)-isomer was a competitive antagonist. These drugs behaved as a competitive antagonist of norepinephrine in the aorta where the efficacy of norepinephrine was large. PMID- 2879953 TI - [Viskaldix for treatment of patients with moderate arterial hypertension. Comparative estimation of hemodynamic changes during treatment with Viskaldix and Stresson]. PMID- 2879954 TI - [Long Q-T syndrome]. PMID- 2879956 TI - [Surgical treatment of post-burn deformities of the dorsum of the foot and ankle joint]. PMID- 2879955 TI - [Somatostatin in the prevention and treatment of complications following pancreatic operations]. PMID- 2879957 TI - [Vascular effect and intraocular pressure-reducing effect of beta blockers]. AB - A study was conducted to investigate the influence of a vasodilating beta receptor blocking substance on IOP in eyes with open-angle glaucoma. The study proceeded from the hypothesis that throttling of the production of aqueous humor by beta blockers and reduction of intraocular pressure is caused by vasoconstriction of the afferent vessels. The authors found that the degree of reduction of intraocular pressure corresponded to the effect of beta blockers routinely applied in glaucoma therapy. However, the duration of the effect was shorter. The above-mentioned hypothesis would thus seem to be disproved. PMID- 2879958 TI - Thyroid-stimulating antibodies in patients with long-term remission of Graves' hyperthyroidism. AB - The persistence of TSH receptor antibodies in Graves' disease despite the remission of hyperthyroidism has been described. Our study was designed to evaluate whether this extends to functionally active stimulators of the thyroid, since the occurrence of thyroid-stimulating antibodies (TSAb) in a euthyroid patient could well have important implications on our understanding of the pathogenetic role of such autoantibodies. Forty-four patients with a previous history of Graves' hyperthyroidism were reexamined after having been in long lasting remission for 3 to 35 years (mean 8 years). Of the patients 16 had been treated by radioiodine, 17 by surgery, and 11 exclusively by antithyroid drugs. The determination of TSAb was based on T3 release from thyroid tissue in vitro to document the final response to these immunoglobulins. TSH-binding inhibiting immunoglobulins (TBII) were evaluated by a radioreceptor assay. TSAb were highly elevated in three of the 44 patients. These three patients showed a normal TSH response to i.v. TRH, suffered from endocrine ophthalmopathy, and had been treated by radioiodine for hyperthyroidism. TBII were found positive in seven patients including the three patients mentioned. The majority of patients positive for TSAb or TBII had been treated by radioiodine and none exclusively by antithyroid drugs. In conclusion, not only TBII but also T3 release-stimulating antibodies may occur in a minority of patients with long-term remission of Graves' hyperthyroidism. However, an absence of hyperthyroidism in these patients despite the presence of such thyroid stimulators seems to be only possible in association with a lack of functional responsiveness of the target organ due to previous administration of destructive therapies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2879959 TI - Influence of beta-blocker coadministration on the kinetics of isosorbide mononitrate and dinitrate. AB - The influence of beta-blocker coadministration on the kinetics of oral isosorbide 5-mononitrate (ISMN) and isosorbide dinitrate (ISDN) was studied in healthy volunteers. In the first study, 12 subjects ingested 20 mg ISMN on three occasions: in the control state, during coadministration of metipranolol (20 mg 3 times daily), or during metoprolol (100 mg twice daily). There were no significant differences among the three phases in peak serum ISMN concentration (470 ng/ml), the time of peak (0.6 h after dose), elimination half-life (4.5 h), or oral clearance (142 ml/min). In the second study, 10 subjects received 20 mg ISDN in the control state and again during coadministration of propranolol (80 mg 3 times daily). There were no differences between the two phases in peak serum ISDN concentration (20 ng/ml) or the time of peak (0.6 h). Propranolol increased, although not significantly, ISDN clearance (16.5 vs 12.3 L/min, P less than 0.1), and had no effect on total area under the curve for ISMN, the major metabolite of ISDN. Thus, therapeutic doses of these beta-blockers have a minimal influence on the kinetics of single doses of ISMN or ISDN in healthy individuals. PMID- 2879962 TI - [Diagnosis of the pseudoperitoneal syndrome]. PMID- 2879960 TI - Influence of propranolol coadministration or cigarette smoking on the kinetics of desmethyldiazepam following intravenous clorazepate. AB - The influence of propranolol coadministration or of cigarette smoking on the kinetics of desmethyldiazepam following a single 20-mg intravenous dose of clorazepate dipotassium was evaluated in healthy volunteers. In Study One, intravenous clorazepate was given once in the control condition, and again during coadministration of propranolol, 80 mg twice daily. Compliance with the prescribed propranolol regimen was verified by measurement of serum propranolol concentrations (mean, 37 ng/ml). In control vs propranolol treatment conditions, there was no significant difference in desmethyldiazepam volume of distribution (1.27 vs 1.23 liters/kg) or in free fraction in serum (1.83 vs 1.80% unbound). There was a small although statistically significant prolongation of desmethyldiazepam half-life (55 vs 61 h, P less than 0.05) and reduction in clearance (0.281 vs 0.247 ml/min/kg, P less than 0.02) attributable to propranolol. In Study Two, desmethyldiazepam kinetics were compared in eight cigarette smokers (mean, 19 cigarettes/day) and in 11 nonsmoking controls matched for age, sex, and body weight. There was no significant difference between controls and cigarette smokers in desmethyldiazepam volume of distribution (1.29 vs 1.34 liters/kg), elimination half-life (55 vs 59 h), clearance (0.284 vs 0.276 ml/min/kg), or free fraction in serum (1.96 vs 1.92% unbound). Thus, propranolol slightly although significantly impairs the clearance of desmethyldiazepam and prolongs its half-life. Cigarette smoking has no apparent influence on desmethyldiazepam kinetics. PMID- 2879961 TI - Treatment of hypertension. Patterns of drug utilization in a metropolitan population. AB - In the Munich Blood Pressure Study (MBS), a cross-sectional study (MBS I) with follow-up (MBS II) of a random sample of 3,198 citizens aged 30-69 (response rate, 69.3%), treatment and control of hypertension were examined. Of the actual hypertensives 59% (221) in MBS II (373) were on drug treatment and about two thirds (150) of those being treated had controlled blood pressure (BP). Women's BP was better controlled than men's. Of the 221 treated hypertensives 85% (188) received types of drugs or drug combinations which were in accordance with the recommendations of the German Hypertension League. However, this did not apply to the prescribed dosages of the various drugs. Of the treated hypertensives 52% were either on a diuretic, on a beta-blocker, or on a combination of both drugs. Rauwolfia alkaloids combined with a diuretic were given to 27%. In 79% of the participants who had received a beta-blocker either alone or in combination with other antihypertensive agents and who still had high BP values, the prescribed beta-blocker dosage was below the recommended daily dose. Fatigue was the most frequently reported symptom, possibly attributable to antihypertensive drug treatment. Electrocardiographic signs of left ventricular hypertrophy were found less frequently in controlled hypertensives, in comparison to treated but uncontrolled hypertensives or untreated hypertensives. PMID- 2879963 TI - [Hormonal function of the pancreatic insular apparatus in patients with chronic alcoholism]. PMID- 2879964 TI - [Derivation of the working equations of a CO2-CO-H2O-H2-N2 gas mixture for the cathode space of an electrolyzer with solid electrolyte taking into account its oxygen extraction]. AB - Equations of thermodynamic equilibrium of the gas mixture CO2-CO--H2O-H2--N2 for the cathode space of the electrolyzer containing a solid electrolyte with extracted oxygen taken into consideration were derived. Equilibrium partial gas pressures, thermal effect of reactions, theoretical voltage of dissociation (the system of equations included 11 unknown parameters) were determined. These parameters are functions of temperature, total pressure of the gas mixture, initial gas composition, and the coefficient characterizing the degree of oxygen transfer from the cathode cell to the anode cell of the electrolyzer. PMID- 2879966 TI - HTLV: the family of human T-lymphotropic retroviruses and their role in leukemia and AIDS. AB - Since 1980 four members of a new retrovirus family called the human T lymphotropic viruses (HTLV-I to -IV) have been discovered and to a large extent characterised. Important common features of these viruses are: transmission by sexual contact or blood, tropism for the T4-lymphocyte and the effects of a viral transactivating gene (tat). They differ in their pathogenic effects, HTLV-I and II being associated with lymphoproliferative malignancies, while HTLV-III is cytopathic and associated with immunosuppression. HTLV-IV is, apparently, not directly highly pathogenic for man. An African origin for this family of viruses is suggested by recent isolations of similar (STLV-I and -III) viruses in Old World primates. Prospects for the possible development of a cross-reactive vaccine have increased since the demonstration of highly conserved DNA sequences in the envelope region of several divergent HTLV-III strains. PMID- 2879965 TI - Biochemical analysis of intact fibroblasts from two cases with methylmalonic acidaemia. PMID- 2879967 TI - Effect of medazepam on benzodiazepine receptors in brain of mice with isolation syndrome. AB - The effect of medazepam in a model of isolation aggression in mice was studied according to Yen et al. It was established that the mean effective dose of medazepam was 250 micrograms/kg and the therapeutic index (LD50:ED50) 6200. The simultaneous biochemical investigations showed a reduction of the affinity and number of benzodiazepine receptors in the brain of aggressive animals. Medazepam 10 mg/kg p.o. led to the restoration of the number of benzodiazepine receptors at a single and 10-day treatment. PMID- 2879968 TI - Human immunodeficiency virus infection in two cohorts of homosexual men: neutralising sera and association of anti-gag antibody with prognosis. AB - Sequential sera from 48 subjects infected with human immunodeficiency virus type I (HIV-I) were examined over 36 months for the presence of neutralising antibodies, and for specific anti-gag (p24) and anti-env (gp41) antibodies to HIV I. Results were interpreted in terms of clinical outcome during the period 1982/3 to 1985/6. HIV-I-infected subjects who remained symptom-free, by comparison with those who manifested AIDS or AIDS-related complex (ARC), had a significantly higher titre of anti-p24 antibodies throughout the 3 years, as measured by competitive enzyme-linked immunosorbent assay and radioimmunoprecipitation. The symptomless subjects also showed a trend towards an increasing neutralising antibody titre with time. There was no relation between anti-gp41 titre and clinical outcome, nor an independent relation between anti-p24 and neutralising titre. A lower or falling titre of anti-p24 antibody was associated significantly with clinical progression, up to 27 months before development of AIDS/ARC. PMID- 2879969 TI - Effect of monounsaturated fatty acids versus complex carbohydrates on high density lipoproteins in healthy men and women. AB - The effects of two strictly controlled diets, one rich in complex carbohydrates, the other rich in olive oil, on serum lipids were studied in healthy men and women. Serum cholesterol levels fell on average by 0.44 mmol/l in the carbohydrate group and 0.46 mmol/l in the olive oil group. HDL cholesterol levels fell by 0.19 mmol/l in the carbohydrate group and rose by 0.03 mmol/l in the olive oil group. Serum triglycerides rose by 0.19 mmol/l in the carbohydrate group and fell by 0.06 mmol/l in the olive oil group. The changes in both HDL and triglycerides were larger in men than in women. These results clearly show that the olive-oil-rich diet, unlike the complex-carbohydrate-rich diet, caused a specific fall in non-HDL cholesterol while leaving serum triglyceride levels virtually unchanged. PMID- 2879970 TI - Inadequacy of chlorproguanil 20 mg per week as chemoprophylaxis for falciparum malaria in Kenya. AB - After treatment with chloroquine and pyrimethamine/sulfadoxine, 118 school children aged 6 to 10 years living near the Kenyan coast were enrolled in a malaria chemoprophylaxis study and followed up for 20 weeks. Children were randomly assigned to receive either chlorproguanil 20 mg weekly (n = 78) or placebo (n = 37). The attack rate of Plasmodium falciparum infection was 42% in chlorproguanil recipients (39.8 episodes per 1000 person-weeks of prophylaxis) and 73% in placebo recipients (69.2 episodes per 1000 person-weeks, p less than 0.02). Sensitivity tests on 36 isolates successfully cultured in vitro showed that all 21 isolates from chloroproguanil recipients were resistant to dihydrofolate-reductase inhibitors, whereas only 3 of 15 isolates from the placebo group were resistant (p less than 10(-6)). Chlorproguanil in a weekly adult dose of 40 mg does not provide adequate prophylaxis against P falciparum in Kenya, probably because drug levels between doses fall below those required to suppress parasites resistant to dihydrofolate-reductase inhibitors. PMID- 2879971 TI - Lymphadenopathy-associated virus type 2 in AIDS and AIDS-related complex. Clinical and virological features in four patients. AB - Lymphadenopathy-associated virus type 2 (HIV 2) was isolated from 3 patients with AIDS and 1 with AIDS-related complex. Clinical features were similar to those in patients infected with HIV 1. Viral isolates were characterised by hybridisation with HIV 1 and HIV 2 DNA probes. HIV 1 and HIV 2 serological studies were performed by enzyme-linked immunosorbent assay (ELISA), western blot, and radioimmunoprecipitation assay. HIV 2 IgG antibodies were detected in all sera. The molecular weights of the most representative HIV 2 proteins were determined by immunoblot. Cross-reactivity was restricted to HIV 1 and HIV 2 core proteins. In all 4 patients the neurotropism of HIV 2 was demonstrated by virus isolation from the cerebrospinal fluid and/or by evidence of intrathecal HIV 2 IgG synthesis. All sera were antibody negative by HIV 1 ELISA. An assay specific for HIV 2 is needed for screening of blood donations and for diagnosis and seroepidemiological study of HIV 2 infection. PMID- 2879973 TI - Detection of a multidrug resistant phenotype in acute non-lymphoblastic leukaemia. AB - Most adult patients with acute non-lymphoblastic leukaemia (ANLL) relapse with drug resistance. Overexpression of a plasma membrane protein, P-glycoprotein, correlates with multidrug resistance in human and animal cell lines. We have detected a multidrug resistance phenotype in two patients with drug resistant ANLL by an immunocytochemical assay using a monoclonal antibody to P glycoprotein. Sequential analysis of peripheral blood samples from both patients showed a progressive increase in both the intensity of staining and the proportion of leukaemic cells that bound antibody as the disease progressed. The assay is simple, and may have prognostic and therapeutic implications. PMID- 2879972 TI - Response of human-immunodeficiency-virus-associated neurological disease to 3' azido-3'-deoxythymidine. AB - Four patients with human-immuno-deficiency-virus-associated neurological disease were treated with 3'-azido-3'-deoxythymidine (AZT). Three (two with chronic dementia, and one with chronic dementia and peripheral neuropathy) improved as assessed by clinical examination, psychometric tests, nerve conduction studies, and/or positron emission tomography; there was no improvement in the fourth patient who presented with paraplegia. These results support the hypothesis that certain AIDS-virus-associated neurological abnormalities are reversible by antiretroviral chemotherapy. PMID- 2879975 TI - Iron deficiency--time for a community campaign? PMID- 2879974 TI - Cholinergic treatment in Alzheimer's disease: encouraging results. PMID- 2879976 TI - Involuntary movement and bacterial meningitis. PMID- 2879977 TI - Chronic diarrhoea in children--a nutritional disease. PMID- 2879978 TI - The chemoreceptor trigger zone revisited. PMID- 2879979 TI - Clinical guidelines, medical litigation, and the current medical defence system. AB - The introduction into National Health Service medical practice of guidelines designed to achieve more effective use of clinical resources is likely to encounter opposition owing to the increasing fear of litigation amongst clinicians. Hospital doctors are unusual amongst salaried professionals in being required to bear the cost of indemnity insurance themselves. The advantages for doctors commonly attributed to this arrangement are insubstantial. A system of no fault compensation is unlikely to be implemented in this country in the foreseeable future. If guidelines are to achieve wide acceptability amongst clinicians, health authorities must accept full legal and financial responsibility for the actions of doctors in their employment, as they currently do for other health service staff. PMID- 2879980 TI - Violence and victims. The contribution of victimology to forensic psychiatry. PMID- 2879981 TI - Comparison of Edmonston-Zagreb and Schwarz strains of measles vaccine given by aerosol or subcutaneous injection. AB - The serological response to measles vaccine was tested in Bangladesh in groups of infants aged 4-6 months who received equal doses of Edmonston-Zagreb or Schwarz vaccine by subcutaneous injection or by aerosol. Seroconversion (as measured by the haemagglutination test) occurred in 62% of infants receiving Edmonston-Zagreb strain by injection compared with only 37% of those receiving Schwarz strain. Seroconversion occurred in 35% of those given Edmonston-Zagreb and 34% of those given Schwarz vaccine by aerosol. Edmonston-Zagreb strain appears more effective than Schwarz vaccine in this population and further studies are indicated in other populations where early measles immunisation is desirable. PMID- 2879983 TI - Short-term cyclosporin and meshed allograft in burns. PMID- 2879982 TI - Successful treatment of chronic active Epstein-Barr virus infection with recombinant interleukin-2. PMID- 2879984 TI - Serum cholesterol and mortality rates. PMID- 2879985 TI - Treatment of acute renal failure, symmetrical peripheral gangrene, and septicaemia with plasma exchange and epoprostenol. PMID- 2879986 TI - Necropsy findings in HTLV-I associated myelopathy. PMID- 2879987 TI - Chronic urticaria associated with coeliac disease. PMID- 2879988 TI - Exercise-induced stridor. PMID- 2879989 TI - Cell lineage in Hodgkin's disease. PMID- 2879990 TI - Oral contraceptive interaction with cyclosporin. PMID- 2879992 TI - Diagnostic significance of quantitative determination of HIV antibody specific for envelope and core proteins. PMID- 2879991 TI - Peptide T in treatment of AIDS. PMID- 2879993 TI - Drug addiction and fear of AIDS. PMID- 2879994 TI - Prevalence of HIV infection in risk groups in Tamilnadu, India. PMID- 2879996 TI - Asthma. PMID- 2879995 TI - Acyclovir in prophylaxis and perinatal varicella. PMID- 2879997 TI - Nursing requirements for children's inpatient care. PMID- 2879998 TI - Psychiatric patients and their notes. PMID- 2879999 TI - Fatty acid beta-oxidation defects and sudden infant death. PMID- 2880000 TI - Streptococcus bovis bacteraemia and its association with alimentary-tract neoplasm. PMID- 2880001 TI - Amoebic research. PMID- 2880002 TI - Water-borne outbreak of Campylobacter laridis-associated gastroenteritis. PMID- 2880003 TI - "Aberrant" MHC class II expression in epithelia. PMID- 2880005 TI - Human parvovirus infections in France 1984-86. PMID- 2880004 TI - Toscana virus infection in United States citizen returning from Italy. PMID- 2880006 TI - Lathyrism. PMID- 2880007 TI - Mesna and total body irradiation. PMID- 2880008 TI - Lyme borreliosis and multiple sclerosis. PMID- 2880009 TI - Human papillomavirus DNA in bronchial squamous cell carcinomas. PMID- 2880010 TI - Low-dose hepatitis B vaccine immunisation in children. PMID- 2880011 TI - Patient's risk of hepatitis B infection from medical staff. PMID- 2880012 TI - Treatment of Crohn's disease and ulcerative colitis with 7S-immunoglobulin. PMID- 2880013 TI - Diagnostic delay due to chlorophyll in oral rehydration solution. PMID- 2880014 TI - Griseofulvin teratology, including two thoracopagus conjoined twins. PMID- 2880016 TI - Congenital dopamine-beta-hydroxylase deficiency. A novel orthostatic syndrome. AB - A woman was referred with severe orthostatic hypotension at the age of 21. Ptosis, skeletal muscle hypotonia, and recurrent hypoglycaemia had been noticed in early childhood. There was noradrenergic denervation and adrenomedullary failure but baroreflex afferents, cholinergic innervation, and adrenocortical function were intact. Noradrenaline and adrenaline were undetectable in plasma, urine, and cerebrospinal fluid (CSF), but dopamine was 7-fold to 12-fold normal in plasma, 4-fold normal in urine, and 20-fold normal in CSF. Measurements of catecholamine metabolites showed further evidence for impairment of noradrenaline and adrenaline biosynthesis due to deficient dopamine-beta-hydroxylation. Dopamine-beta-hydroxylase was undetectable in plasma and CSF. Physiological and pharmacological stimuli of sympathetic neurotransmitter release caused increases in plasma dopamine rather than plasma noradrenaline. PMID- 2880015 TI - Linoleic and eicosapentaenoic acids in adipose tissue and platelets and risk of coronary heart disease. AB - The relation between the fatty-acid composition of adipose tissue and platelet membranes and the estimated relative risk of coronary heart disease (CHD) was examined in a case-control study of new angina pectoris (AP) and first acute myocardial infarction (AMI). There were progressive inverse relations between adipose linoleic acid and platelet-membrane eicosapentaenoic acid and the estimated relative risk of AP. These relations were statistically independent of each other and traditional CHD risk factors. For AMI there was a progressive inverse relation between adipose linoleic acid and the estimated relative risk, but it was confounded by smoking habit. Smokers consume less linoleic acid than non-smokers. Although eicosapentaenoic acid in platelet membranes was lower in AMI patients than in controls, this difference was not significant. The estimated proportionate increase in risk of AP, independent of other CHD risk factors, was 1.2 (1.1-1.3) for a 1% decrease in linoleic acid or a 0.1% decrease in eicosapentaenoic acid. PMID- 2880017 TI - Umbilical artery flow velocity waveforms in high-risk pregnancy. Randomised controlled trial. AB - 300 patients at high fetal risk (mean gestational age 34 wk) were randomised to a group for antenatal doppler umbilical artery waveform studies and a control group. The timing of delivery was similar in the control and doppler-report available groups overall. However, in the report group obstetricians allowed the pregnancies of those not selected for elective delivery to continue longer. There was no difference in the rates for elective delivery (induction of labour or caesarean section) in the two groups, whereas among those who went into labour (induced or spontaneous) emergency caesarean section was more frequent in the control group (23%) than in the report group (13%). Fetal distress in labour was also more common in the control group. Babies from the control group spent longer in neonatal intensive care (level 3) and needed more respiratory support than did those in the report group. The findings indicate that the availability of doppler studies leads to better obstetrical decision making. PMID- 2880018 TI - Growth failure and growth-hormone deficiency after treatment for acute lymphoblastic leukaemia. AB - In a study of 77 children who had been treated for acute lymphoblastic leukaemia (ALL) with an LSA2L2 (Memorial Sloan-Kettering) chemotherapy protocol plus radiotherapy (24 Gy) as cranial prophylaxis, growth was examined 3.0-9.5 years after diagnosis. The children's growth slowed and they crossed height percentiles towards the end of or after treatment. The Z-score, which reflects the deviation of height measurements from the population mean, was used to assess height change. The mean Z-score was 0.16 at diagnosis, -0.30 2 years later, -0.71 4 years later, and -1.37 6 years later. Height for age had fallen by more than 1 standard deviation of the population mean in 32% of survivors 4 years after diagnosis and in 71% 6 years after diagnosis. Younger children and those tall for age at diagnosis were more severely affected. Growth-hormone (GH) response to standard provocation tests was measured in 46 patients; 30 had partial or complete GH deficiency. Mean pulsatile GH secretion was low in the 34 patients tested. Cranial irradiation is probably the most important causative factor in the development of GH deficiency in survivors of ALL. PMID- 2880019 TI - Dengue virus isolation by antibody-dependent enhancement of infectivity in macrophages. AB - Acute-phase serum samples collected during an outbreak of dengue fever and dengue haemorrhagic fever in Penang, Malaysia, were tested by a method involving antibody-dependent enhancement of infectivity in the mouse macrophage-like cell line, P388D1. 58 of 71 (81.7%) serologically positive cases yielded virus. PMID- 2880020 TI - Kawasaki disease: a novel feline virus transmitted by fleas? PMID- 2880022 TI - A sound approach to the diagnosis of acute appendicitis. PMID- 2880023 TI - Metabolic bone disease of prematurity. PMID- 2880021 TI - Management of orthostatic hypotension. PMID- 2880024 TI - Rumination. PMID- 2880025 TI - Infections of the dural venous sinuses. PMID- 2880026 TI - Health services for inner London. PMID- 2880027 TI - Introducing medicine to tomorrow's doctors. PMID- 2880029 TI - Histiocytosis syndromes in children. Writing Group of the Histiocyte Society. PMID- 2880028 TI - The "epidemic" of anorexia nervosa: another medical myth? AB - Examination of data on patients admitted to psychiatric facilities in England in 1972-81, inclusive, with a main diagnosis of anorexia nervosa showed that first admissions for women rose significantly with time--age-period-cohort analysis showed that this was due entirely to an increase in the number of young women in the population rather than to an increase in risk of morbidity. There were significant increases with time in the readmission rates for both sexes. For the women, these were due to a complex interrelation between age, period, and cohort effects. This rising readmission rate may have contributed to the widely held impression that the incidence of anorexia nervosa has risen sharply. PMID- 2880030 TI - Cold-related deaths in some developed countries. PMID- 2880031 TI - Acyclovir in accelerated phase of Chediak-Higashi syndrome. PMID- 2880032 TI - Prostaglandins, smoking, and duodenal ulcers. PMID- 2880033 TI - Prenatal diagnosis of choroid plexus cysts. PMID- 2880034 TI - Tubal ovum transfer: a Catholic-approved alternative to in-vitro fertilisation. PMID- 2880035 TI - Carboplatin and neuroblastoma. PMID- 2880036 TI - Non-invasive measurement of cardiac output. PMID- 2880037 TI - Prophylactic role for antibodies to Escherichia coli J5. PMID- 2880038 TI - Haemofiltration in management of patients with acute renal failure complicated by raised intracranial pressure. PMID- 2880039 TI - Permanent brain damage after cardiac surgery. PMID- 2880040 TI - Prostatic cancer, butchers, and androgens. PMID- 2880041 TI - Nutritional approach to oesophageal cancer in Scotland. PMID- 2880042 TI - Suicide attempts and the menstrual cycle. PMID- 2880043 TI - Postviral fatigue syndrome. PMID- 2880044 TI - Asthma and other obstructive lung diseases. PMID- 2880045 TI - Ergotism as complication of thromboembolic prophylaxis with heparin dihydroergotamine. PMID- 2880046 TI - Graft-versus-leukaemia effect of graft-versus-host disease. PMID- 2880047 TI - Refuseniks and UK/USSR medical cooperation. PMID- 2880048 TI - Access to personal medical records. PMID- 2880049 TI - Samples for breath alcohol analysis. PMID- 2880050 TI - Serum acid proteolytic activity in Reye syndrome. PMID- 2880051 TI - Clinical justification for cerebrospinal fluid investigation. PMID- 2880052 TI - Pancreatic stone protein, protein X, and thread protein. PMID- 2880054 TI - AIDS and health-care workers. PMID- 2880053 TI - HIV-2 infection in two homosexual men in France. PMID- 2880055 TI - Peripheral neuropathy after heatstroke. PMID- 2880056 TI - Transtelephonic monitoring of patients with implanted neurostimulators. PMID- 2880057 TI - First-degree atrioventricular block induced by oral cimetidine. PMID- 2880058 TI - Allergy testing. PMID- 2880059 TI - Whole blood exchange as treatment for legionellosis. PMID- 2880060 TI - Unexplained stillbirth. PMID- 2880061 TI - Family with neuromuscular disorder where mode of inheritance was resolved by RFLP analysis. PMID- 2880062 TI - Achievement of thrombolysis at home in cases of acute myocardial infarction. PMID- 2880063 TI - First picture of erythema infectiosum? PMID- 2880065 TI - Will all addicted pregnant women have their babies taken into care? PMID- 2880064 TI - Removal and replacement of Tenckhoff catheters. PMID- 2880066 TI - Oral ciprofloxacin compared with conventional intravenous treatment for Pseudomonas aeruginosa infection in adults with cystic fibrosis. AB - 40 adult patients with cystic fibrosis (CF) were admitted to hospital with acute exacerbations of infection associated with isolation of Pseudomonas aeruginosa from sputum. The patients were randomly allocated (20 per group) to receive intravenous azlocillin 5 g and gentamicin 80 mg, or oral ciprofloxacin 500 mg. Both treatments were given three times a day for 10 days. The patients were assessed on days 1 and 10, and at 6 weeks. There was a significant improvement in lung function between days 1 and 10 in both groups (p less than 0.001). Significant improvement was maintained at 6 weeks after ciprofloxacin but not in the intravenous group. Improvement after ciprofloxacin was superior at day 10. Sputum weight decreased in both groups (p less than 0.001). Patient-recorded symptoms also improved in both groups. There was no serious toxicity or side effects. Drug resistant organisms were isolated no more frequently after ciprofloxacin than after intravenous therapy. 17 of the ciprofloxacin-treated patients said they preferred oral treatment to intravenous therapy. Oral ciprofloxacin is a useful short-term treatment for patients with CF who are infected with Ps aeruginosa. PMID- 2880067 TI - Autoimmunity to insulin receptor and hypoglycaemia in patient with Hodgkin's disease. AB - A 76-year-old man with fasting hypoglycaemia had impaired in-vitro binding of insulin to erythrocyte receptors. The immunoglobulin fraction of his plasma inhibited binding of insulin to normal donor erythrocytes in vitro. Autoantibodies may have stimulated the insulin receptor and produced hypoglycaemia. Hodgkin's disease developed and may have induced the autoimmunity. The hypoglycaemia did not respond to plasmapheresis or azathioprine alone, but it remitted after the addition of prednisolone, and the erythrocyte receptor binding of insulin became normal. PMID- 2880070 TI - Immunoregulation and prognosis in myeloma. AB - In patients in the plateau phase of myeloma, expression of the light-chain isotype concordant with the malignant paraprotein on peripheral-blood lymphocytes is suppressed. This light-chain-isotype suppression (LCIS) is lost when the disease becomes progressive. LCIS is identified by quantifying kappa and lambda cells in peripheral blood in an indirect immunofluorescence assay. In 27 patients presenting with myeloma, the prognosis was significantly better for patients with LCIS at presentation than for those without. Bone-marrow mononuclear cells, studied in 7 patients with myeloma and LCIS in peripheral blood, did not show LCIS. PMID- 2880068 TI - Hypoglycaemia due to an insulin-receptor antibody in Hodgkin's disease. AB - Severe fasting hypoglycaemia developed in a patient with Hodgkin's disease after many courses of chemotherapy. Her serum contained a factor which stimulated glucose uptake by rat adipocytes, and this factor was found in the immunoglobulin fraction. The serum also displaced insulin bound to human erythrocytes and both precipitated and phosphorylated insulin receptors extracted from human placenta. The insulin-like substance is probably an antibody to the insulin receptor. PMID- 2880069 TI - Effect of a ginkgolide mixture (BN 52063) in antagonising skin and platelet responses to platelet activating factor in man. AB - Antagonism of the effects of platelet activating factor (PAF) by the ginkgolide mixture BN 52063 was assessed in a double-blind, placebo-controlled, crossover study in 6 normal subjects. Weal and flare responses to 400 ng PAF, examined 2 h after ingestion of BN 52063 (80 mg, 120 mg) were inhibited in a dose-related manner. After 120 mg the flare area was reduced by a mean 62.4% (p less than 0.005) and the weal volume by a mean 60% (p less than 0.05). Both doses of BN 52063 significantly inhibited PAF-induced platelet aggregation in platelet-rich plasma (p less than 0.001). In vitro, BN 52063 inhibited PAF-induced but not ADP induced platelet aggregation. Thus BN 52063 seems to be an antagonist of PAF in man. PMID- 2880071 TI - Maternal health in subsaharan Africa. PMID- 2880073 TI - The forgotten people. PMID- 2880072 TI - Pharmaceutical funds for clinical research: a mixed blessing. PMID- 2880074 TI - Allopurinol for calcium oxalate stones? PMID- 2880075 TI - HIV seroepidemiology. PMID- 2880076 TI - Emerging pattern of Lyme disease in the United Kingdom and Irish Republic. AB - In the past year there have been 68 cases of Lyme disease in the United Kingdom and Republic of Ireland. 41 patients had erythema chronicum migrans, and 8 of them had associated neurological disease. 13 further patients presented with neurological disease without a preceding skin lesion. Myocarditis was present in 1 patient. Ixodes ricinus was confirmed as the vector for Lyme disease. In two areas deer were found to be infected by Borrelia burgdorferi, the causative organism of Lyme disease. 86% of 45 deer sera tested had significant antibody titres against B burgdorferi. PMID- 2880077 TI - Back pain--a presentation of metastatic testicular germ cell tumours. AB - 9 patients (21%) from a total of 42 young men with testicular germ cell malignancy had back pain as a major presenting symptom; 2 had back pain without unilateral testicular enlargement. Time to correct diagnosis from first visit to a doctor was significantly longer in those with back pain than in those with testicular symptoms. All patients with back pain had para-aortic node metastases. Young men with back pain should be examined for testicular disease and should also be asked about past testicular abnormalities. PMID- 2880078 TI - The Canadian community hospital. PMID- 2880079 TI - Diltiazem for tardive dyskinesia. PMID- 2880080 TI - Tardive dystonia: which way do schizophrenics twist? PMID- 2880081 TI - Significance of isolated yolk sac visualised by ultrasonography. PMID- 2880082 TI - Intrauterine insemination. PMID- 2880083 TI - Prednisolone pharmacokinetics and steroid psychosis. PMID- 2880085 TI - Testing cerebrospinal fluid. PMID- 2880084 TI - Bethanecol chloride in treatment of stuttering. PMID- 2880087 TI - Fine-catheter aspiration and the acute abdomen. PMID- 2880088 TI - Giving up smoking and converting to pipe or cigars. PMID- 2880086 TI - Consumption of quinine hydrochloride in tonic water. PMID- 2880089 TI - Human gene cloning and disease analysis. PMID- 2880090 TI - Recombination between Duchenne and pERT87 variants. PMID- 2880091 TI - Dietary lipopolysaccharides as arthritogenic antigen? PMID- 2880092 TI - Control of epidemic methicillin-resistant Staphylococcus aureus. PMID- 2880093 TI - Systemic candidiasis. PMID- 2880094 TI - Which spatula for cervical cytology? PMID- 2880095 TI - Ecological treatment of bacterial vaginosis. PMID- 2880096 TI - Investigating hypomagnesaemia. PMID- 2880097 TI - HLA antigens and germ-cell tumours. PMID- 2880098 TI - Standardising the anti-cardiolipin antibody test. PMID- 2880099 TI - Advertising claims and the Medicines Act. PMID- 2880100 TI - Diagnostic process. PMID- 2880101 TI - Body history. PMID- 2880103 TI - Viral cause of Kaposi's sarcoma? PMID- 2880102 TI - RFLP for linkage analysis of fragile X syndrome. PMID- 2880105 TI - Neopterin and beta 2-microglobulin as markers for AIDS. PMID- 2880104 TI - Methimazole antagonises HLA-DR3 suppression of AIDS. PMID- 2880106 TI - Inactivation of human immunodeficiency, herpes simplex, and vaccinia viruses by sodium oxychlorosene. PMID- 2880108 TI - Delayed diagnosis of pneumococcal sepsis post-splenectomy. PMID- 2880107 TI - Genetic haemochromatosis and congenital spherocytosis. PMID- 2880109 TI - Differential diagnosis in child sexual abuse. PMID- 2880110 TI - Care of the newborn in developing countries. PMID- 2880111 TI - Enzymological diagnosis of primary hyperoxaluria type 1 by measurement of hepatic alanine: glyoxylate aminotransferase activity. AB - A deficiency of activity of the peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT,EC 2.6.1.44)has been found in the livers of six patients with primary hyperoxaluria type 1 (PH), including three in whom the tissue was obtained by percutaneous needle biopsy. AGT activity, assayed in unfractionated liver tissue, ranged from 11 to 47% of the mean control value, and appeared to be related to the clinical severity of PH and to several biochemical variables which indicate the degree of pathophysiological derangement. There was no difference between patients and controls in the activities of glutamate: glyoxylate aminotransferase (GGT, EC 2.6.1.4) or catalase (EC 1.11.1.6). In the five most severe cases residual AGT activity could be largely accounted for by the crossover from another enzyme, presumably GGT. PH can be diagnosed using percutaneous hepatic needle biopsy and assay of AGT, whose activity may be useful in determining the prognosis and likely severity of the disease. PMID- 2880112 TI - Characterisation of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen. AB - Autoantibodies against a soluble liver antigen (SLA) were detected in 23 patients with HBsAg-negative chronic active hepatitis (CAH) but not in 502 patients with various other hepatic and non-hepatic disorders or 165 healthy blood donors. Anti SLA-positive serum samples were negative for antinuclear and liver-kidney microsomal antibodies, markers of two subgroups of autoimmune-type CAH, 6 anti SLA-positive patients were negative for all autoantibodies sought. Most of the anti-SLA-positive patients were young women (2 men, 21 women; mean age 37 years) with hypergammaglobulinaemia (mean 3.2 g/l, range 1.8-5.3 g/l); 18 of the 23 patients had received immunosuppressive treatment and all responded well. Anti SLA titres declined during therapy, corresponding to disease activity. Anti-SLA cannot be detected by immunofluorescence. SLA is not organ-specific or species specific, but the highest concentrations were found in liver and kidney. Anti-SLA autoantibodies characterise a third subgroup of autoimmune-type CAH and will allow a better differentiation of HBsAg-negative CAH which has therapeutic consequences. PMID- 2880113 TI - Long-term survival in haemodialysis patients. AB - Survival rates and causes of death were analysed for 177 patients who started dialysis between 1970 and 1975. 99 patients survived 5 years of treatment, and at this stage 74 had functioning transplants; thereafter, only 4 changed between treatment by dialysis and transplantation. For patients surviving for 5 years those treated by dialysis and those treated by transplantation had a similar probability (+/- standard error) of surviving to 10 years (0.84 +/- 0.07 v 0.82 +/- 0.04), but the probability of surviving to 15 years was lower for dialysis patients than for transplant patients (0.31 +/- 0.14 v 0.63 +/- 0.08; p less than 0.05). Infection, particularly with Staphylococcus aureus, was an important cause of late mortality in dialysis patients. PMID- 2880116 TI - Autologous bone-marrow transplantation. PMID- 2880114 TI - Effect of oestrogen and testosterone implants on psychological disorders in the climacteric. AB - In a double-blind trial oestradiol, oestradiol/testosterone, or placebo implants were assessed for their effects on psychological symptoms in women attending a menopause clinic. After two months, women receiving active treatment scored better than the placebo group on a self-rating scale of distress, on anxiety, and on depression (p less than 0.05). Postmenopausal but not perimenopausal women improved after placebo, and at 4 months the scores in the three groups no longer differed significantly. PMID- 2880115 TI - Rapid and safe termination of supraventricular tachycardia in children by adenosine. AB - Adenosine (0.05-0.25 mg/kg intravenously) successfully terminated resistant supraventricular tachycardia (SVT) in three seriously ill newborn infants and one older child. Termination of tachycardia was achieved in each case within 20 s. Adenosine, unlike many other anti-arrhythmic agents, has no substantial negative inotropic effect under these circumstances and may become the drug of choice in haemodynamically compromised children with SVT. However, it has no value in prophylaxis against recurrent SVT. PMID- 2880117 TI - Haemorrhagic cystitis after radiotherapy. PMID- 2880118 TI - Vitamin D supplementation in the elderly. PMID- 2880119 TI - Diazepam binding inhibitor. PMID- 2880120 TI - Tourette syndrome. PMID- 2880121 TI - Future hunger? PMID- 2880122 TI - Causes of death in diabetic patients with impaired renal function. An audit of a hospital diabetic clinic population. AB - Of over 2000 diabetic patients whose serum creatinine had been measured regularly, 107 died between January, 1983, and March, 1985, and 27 (median age at death 66 years) had renal impairment (serum creatinine over 130 mumol/l). Cause of death was determined from clinical and necropsy data. 11 died of cardiovascular disease and 10 of causes unrelated to cardiac or renal disease; in only 6 was renal impairment the main cause of death. All 6 had severe physical and/or social disabilities and 2 were over the age of 75. Median serum creatinine in patients who died was 269 mumol/l (range 135-1135 mumol/l) and exceeded 500 mumol/l in only 5. Of the few patients who would have received RRT under a more liberal dialysis policy, all had severe physical disabilities. PMID- 2880123 TI - Respiratory allergy to inhaled bat guano. AB - In the Sudan many asthmatic patients attribute their symptoms to inhalation of bat droppings. Design of the roofs of many Sudanese buildings allows black bats to roost; guano drops through cracks in the ceiling into the rooms below where it can be inhaled and cause allergic respiratory disorders. Seven atopic patients seen at Sennar Hospital with bat-related case-histories were investigated. Six had bronchial asthma and allergic rhinitis and one had asthma alone. Extracts of yellow hairy bat, black bat, and bat droppings were made. All seven patients had a positive skin prick test and specific IgE antibodies (RAST) to bat droppings. Three patients also had a positive RAST to both yellow and black bats and one patient to yellow bat. Droppings are probably the major allergen source in bat related respiratory allergy. PMID- 2880124 TI - European accelerator for radiotherapy with charged ions. PMID- 2880125 TI - Tardive myoclonus. PMID- 2880126 TI - Tetrahydroaminoacridine and Alzheimer's disease. PMID- 2880127 TI - Cautions about condoms in prevention of AIDS. PMID- 2880128 TI - Sleep deprivation, dieting, and depression markers. PMID- 2880129 TI - Anti-HIV testing on urgent specimens. PMID- 2880131 TI - Dietary protein restriction in chronic renal failure. PMID- 2880130 TI - Efficacy of five enzyme immunoassays for antibody to HIV in detecting antibody to HTLV-IV. PMID- 2880132 TI - Heterosexuals importing HIV from Africa. PMID- 2880133 TI - Direct intraperitoneal insemination. PMID- 2880134 TI - Occupational exposure to 1,3-butadiene. PMID- 2880135 TI - Intrathecal interferon, indomethacin, and multiple sclerosis. PMID- 2880136 TI - Acetaldehyde-modified albumin as hepatotoxic factor. PMID- 2880137 TI - Intrathecal mitozantrone. PMID- 2880138 TI - Legal interference and clinical freedom. PMID- 2880139 TI - Ethics of tissue typing on live organ donors. PMID- 2880140 TI - Teicoplanin-resistant coagulase-negative staphylococci. PMID- 2880141 TI - Rabbit (to replace human) brain material in anticoagulant control. PMID- 2880142 TI - Chronic lymphocytic leukaemia in twin sisters: monozygous but not identical. PMID- 2880143 TI - CSF lactate in falciparum malaria patients. PMID- 2880144 TI - Percutaneous laser angioplasty with sapphire tips. PMID- 2880145 TI - Corneal transplant in boy with nephropathic cystinosis. PMID- 2880146 TI - Gastroenteritis due to Kanagawa negative Vibrio parahaemolyticus. PMID- 2880147 TI - 24-hour monitoring of oesophageal pH in outpatients. PMID- 2880148 TI - Parkinsonism and industrial chemicals. PMID- 2880149 TI - False positive identifications of Escherichia coli O157. PMID- 2880150 TI - Prostaglandins for peptic ulcer. PMID- 2880151 TI - Corticotropin releasing factor in Alzheimer's disease. PMID- 2880152 TI - Holiday balcony falls resulting in spinal cord injury. PMID- 2880153 TI - Mycobacteria in sputum and soil ingestion. PMID- 2880154 TI - Blue sclerae and iron deficiency in general practice. PMID- 2880155 TI - Digoxin-like immunoreactive factor, corticotropin-releasing factor, and pregnancy. PMID- 2880156 TI - Acute nephritis complicating Milroy's disease. PMID- 2880157 TI - Cardiac output and Christmas lunch. PMID- 2880158 TI - Human papillomavirus DNA and oral mucosa. PMID- 2880159 TI - "Serious professional misconduct" in relation to private treatment of drug dependence. PMID- 2880160 TI - Risk factors for seroconversion to human immunodeficiency virus among male homosexuals. Results from the Multicenter AIDS Cohort Study. AB - 2507 homosexual men who were seronegative for human immunodeficiency virus (HIV) at enrollment were followed for six months to elucidate risk factors for seroconversion to HIV. 95 (3.8%) seroconverted. Of men who did not engage in receptive anal intercourse within six months before baseline and in the six-month follow-up period, only 0.5% (3/646) seroconverted to HIV. By contrast, of men who engaged in receptive anal intercourse with two or more partners during each of these successive six-month intervals, 10.6% (58/548) seroconverted. No HIV seroconversions occurred in 220 homosexual men who did not practise receptive or insertive anal intercourse within twelve months before the follow-up visit. On multivariate analysis receptive anal intercourse was the only significant risk factor for seroconversion to HIV, the risk ratio increasing from 3-fold for one partner to 18-fold for five or more partners. Furthermore, data for the two successive six-month periods show that men who reduced or stopped the practice of receptive anal intercourse significantly lowered their risk of seroconversion to 3.2% and 1.8%, respectively. Receptive anal intercourse accounted for nearly all new HIV infections among the homosexual men enrolled in this study, and the hazards of this practice need to be emphasised in community educational projects. PMID- 2880161 TI - Double-blind multicentre comparison of omeprazole and ranitidine in the treatment of reflux oesophagitis. AB - Omeprazole 60 mg once daily was compared with ranitidine 150 mg twice daily in an endoscopically-controlled, double-blind randomised trial in 51 outpatients with erosive or ulcerative reflux oesophagitis (grade 2 or 3). Endoscopy was repeated after 4 weeks and, in the absence of healing, again after 8 weeks. Symptoms were assessed before entry and after 2, 4, and 8 weeks. Patients who were unhealed after 8 weeks were blindly switched to the other drug and treatment was continued for another 4 to 8 weeks. The healing rate (change to grade 0 or 1 oesophagitis) after 4 weeks was 19 of 25 patients treated with omeprazole and 7 of 26 patients treated with ranitidine (p = 0.002). The corresponding figures after 8 weeks were 22 of 25 and 10 of 26 (p = 0.001). The higher healing rate with omeprazole was reflected in a significantly faster and stronger improvement of reflux symptoms. 13 patients, who were unhealed after 8 weeks on ranitidine, were healed after switching treatment. Healing was achieved in 1 of 3 patients who were switched to ranitidine. There were no adverse events or changes in laboratory variables of clinical importance. Omeprazole is superior to ranitidine in the short-term treatment of reflux oesophagitis. PMID- 2880162 TI - Effect of indomethacin on arterial oxygenation in critically ill patients with severe bacterial pneumonia. AB - The effect of indomethacin (1 mg/kg) on gas exchange was studied in ten patients with hypoxaemic respiratory failure precipitated by bacterial pneumonia. Mean arterial oxygen tension (PaO2) improved significantly (79 +/- 16 mm Hg to 98 +/- 20 mm Hg) but the response varied between patients: five showed substantial responses (27-42 mm Hg), three lesser responses (7-9 mm Hg), and two no response. Similar changes were found in the alveolar-arterial oxygen gradient and the ratio of PaO2 to fractional inspired oxygen concentration. In two responders studied further, PaO2 had fallen to baseline values 4-6 h later and a repeat indomethacin challenge again increased PaO2 by greater than 25 mm Hg with concomitant changes in pulmonary shunt. There were no significant changes in the other gas-exchange or haemodynamic variables measured and there was no clear reason for the variability in response to indomethacin. These results suggest a role for products of the cyclo-oxygenase pathway of arachidonic acid metabolism in the pathogenesis of hypoxaemia in patients with severe bacterial pneumonia. PMID- 2880163 TI - Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease. AB - Serum samples taken on admission from 79 patients with meningococcal meningitis, septicaemia, or both, were examined in a highly sensitive bioassay for tumour necrosis factor (TNF). TNF was detected in samples from 10 of 11 patients who died but from only 8 of 68 survivors. All 5 patients with serum TNF levels over 440 units/ml (corresponding to 0.1 ng/ml recombinant TNF) died. PMID- 2880164 TI - Intestinal toxicoinfection by Clostridium botulinum type F in an adult. Case associated with Guillain-Barre syndrome. AB - A 27-year-old man with type F botulism (classification undetermined) had two episodes of botulinum toxaemia with identification of botulinum toxin and Clostridium botulinum organisms in faecal specimens during a three-month stay in hospital. Between these clinical episodes neither toxin nor Cl botulinum could be demonstrated. The illness was severe with quadriplegia, respiratory insufficiency, and bowel paralysis. In addition the patient had sensory abnormalities and a raised protein in the cerebrospinal fluid. The results demonstrate for the first time in detail an intestinal colonisation with and multiplication of C botulinum organisms and in-vivo production of toxin in an adult. The clinical findings at first pointed to Guillain-Barre syndrome, and it is suggested that patients with this syndrome should be examined for botulinum toxin in serum and for toxin and organisms in stool. PMID- 2880166 TI - Screening for drugs of abuse. PMID- 2880165 TI - Rapid, easy, and economical screening test for antibodies to human immunodeficiency virus. AB - A new dot enzyme immunoassay (EIA) with a conserved portion of the envelope protein of the human immunodeficiency virus (HIV) as antigen has been designed for use in areas with few laboratory facilities and by personnel with little laboratory experience. Sera were tested in 263 subjects who had AIDS or AIDS related complex or were at-risk or not-at-risk of AIDS from the USA, Africa, and Asia/Oceania. The dot EIA was 100% sensitive in the American subjects, and there were only 2 false negatives in the others, both of which were negative by commercial EIA. The test is simple to perform, economical, rapid (30 min), and stable. PMID- 2880168 TI - The practice of blood transfusion. PMID- 2880169 TI - Monkeypox in Africa: future health hazard or public health nuisance? PMID- 2880167 TI - Ill-treatment of children. PMID- 2880170 TI - Lactate transporter defect: a new disease of muscle? PMID- 2880171 TI - Calcium supplements: does the milkman know best? PMID- 2880172 TI - The challenge of malaria vaccine: trials and tribulations. PMID- 2880173 TI - Recovery from physical disability after stroke: normal patterns as a basis for evaluation. AB - In 368 patients with residual hemiplegia after stroke, monitoring of recovery over eight weeks showed a distinct time-related pattern. Patterns of this sort could provide useful baselines in various conditions entailing physical disability, allowing comparison of individual scores with the average for that phase of the illness, the setting of precise goals, and the examination of factors that influence recovery. PMID- 2880174 TI - The Shadow-Line in surgery. PMID- 2880175 TI - Infant carrying, breast feeding, and mother-infant relations. PMID- 2880176 TI - Bat rabies in Denmark. PMID- 2880177 TI - Decrease in acute hepatitis B incidence in England and Wales in 1985-86. PMID- 2880178 TI - Long-term follow-up after bone-marrow transplantation in acute lymphoblastic leukaemia. PMID- 2880179 TI - Simplified cooling bed for heatstroke. PMID- 2880180 TI - Conservative treatment of ectopic pregnancy by transvaginal aspiration under sonographic control and methotrexate injection. PMID- 2880181 TI - Serum cholesterol, blood pressure, and mortality. PMID- 2880182 TI - Ultrastructure of liver in inherited disorders of fat oxidation. PMID- 2880183 TI - Oral contraceptives and breast cancer. PMID- 2880184 TI - Chromosome 21q21 sublocalisation of gene encoding beta-amyloid peptide in cerebral vessels and neuritic (senile) plaques of people with Alzheimer disease and Down syndrome. PMID- 2880185 TI - Vascular malformations and hypogammaglobulinaemia. PMID- 2880186 TI - Never on a Sunday: programming for IVF-ET and GIFT. PMID- 2880188 TI - Diagnosis: the need for demystification. PMID- 2880187 TI - Ultrasound-guided peritoneal oocyte and sperm transfer (POST) PMID- 2880189 TI - Fitness for anaesthesia: who decides? PMID- 2880190 TI - Acupuncture. PMID- 2880191 TI - AIDS and obstetrics. PMID- 2880192 TI - Cold-related deaths in Britain. PMID- 2880193 TI - Prescribing iron to combat deprivation. PMID- 2880194 TI - HIV-1 and HIV-2 double infection in French homosexual male with AIDS-related complex (Paris, 1985) PMID- 2880195 TI - Allergy testing. PMID- 2880196 TI - Parathyroid hormone, electrolytes, and blood pressure. PMID- 2880197 TI - Valproate hepatotoxicity. PMID- 2880198 TI - Gold-induced leucopenia may predict a similar adverse reaction to sulphasalazine. PMID- 2880199 TI - Encephalopathy with rapid infusion ifosfamide/mesna. PMID- 2880200 TI - Exacerbation of rheumatoid synovitis by iron-dextran infusion. PMID- 2880201 TI - Does Down syndrome support homocysteine theory of arteriosclerosis? PMID- 2880202 TI - Allergy in cystic fibrosis nurses to pancreatic extract. PMID- 2880204 TI - Recombinant human erythropoietin in anaemic patients on haemodialysis. PMID- 2880203 TI - Mesothelioma in manufacturers of asbestos-containing cigarette filters. PMID- 2880205 TI - IgM serology for rubella and human parvovirus B19. PMID- 2880206 TI - Misoprostol, smoking, and duodenal ulcer healing rates. PMID- 2880207 TI - Non-endoscopic relief of oesophageal obstruction. PMID- 2880208 TI - Isotonic methotrimeprazine by continuous infusion in terminal cancer care. PMID- 2880210 TI - Strict metabolic control and diabetic nephropathy. PMID- 2880209 TI - Prenatal diagnosis of Bartter syndrome. PMID- 2880211 TI - Three-year ban by GMC upheld: possibility of revocation or variation on petition by doctor during sentence. PMID- 2880212 TI - Damages awarded for 25% loss of chance of full recovery. PMID- 2880213 TI - Immunotherapy versus chemotherapy in localised cutaneous leishmaniasis. AB - In a randomised trial a combination vaccine consisting of live BCG together with killed leishmania promastigotes was compared with a standard antimonial regimen in 94 patients with localised cutaneous leishmaniasis. Three vaccinations over 32 weeks gave a similar cure rate (94%) to three 20-day courses of meglumine antimonate. In the immunotherapy group side-effects were few (5.8%) and slight whereas in the chemotherapy group they were frequent (52.4%) and often serious. Immunotherapy is a low-cost, low-risk alternative to chemotherapy in localised cutaneous leishmaniasis, applicable by primary health services in rural areas. PMID- 2880214 TI - Double-blind randomised trial of intravenous glycerol in acute stroke. AB - The effects of intravenous glycerol in elderly patients with recent onset of acute ischaemic stroke were evaluated in a double-blind randomised controlled trial. 173 patients received either 500 ml of a 10% solution of glycerol in physiological saline or 500 ml of physiological saline administered intravenously over 4 h daily for 6 consecutive days. The number of deaths within the first week was 10 (12%) in the glycerol group versus 26 (30%) in the controls. Subsequent mortality up to 12 months was similar in the two groups and a survival analysis confirmed a beneficial effect of treatment (p less than 0.02). The neurological and functional recovery of survivors, their length of hospital stay, and the proportion able to return to live in their own home were similar in the two groups. The improvement in survival time with glycerol was achieved without serious adverse effects and without an increase in the proportion of survivors with severe residual disability. PMID- 2880215 TI - Prevalence of human T-lymphotropic retroviruses type III (HIV) and type IV in Ivory Coast. AB - Serological investigations in the Ivory Coast indicate that, despite the rarity of overt acquired immunodeficiency syndrome (AIDS), human immunodeficiency virus (HIV) is widely prevalent. So also is human T-lymphotropic virus type IV (HTLV IV). The highest rates of HIV and HTLV-IV seropositivity were observed in female prostitutes. These findings suggest that, like HIV, HTLV-IV can be transmitted by heterosexual contact, and that the mobility of prostitutes may be an important factor in spread of the retroviruses in Africa. The incidence of HIV-associated AIDS in the Ivory Coast is likely to rise sharply in the next few years. PMID- 2880216 TI - Increased frequency of Epstein-Barr virus excretion in patients with new daily persistent headaches. AB - In a case-control study 27 (84%) of 32 patients with new daily persistent headaches (NDPH) and 8 (25%) of 32 controls had evidence of Epstein-Barr virus (EBV) "active" infection, as demonstrated by EBV excretion and/or early antigen titre above 1:32. 20 (62%) patients and 4 (12%) controls were excreting EBV in the oropharynx, as determined by a dot hybridisation assay. The mean titre of IgG antibodies to early antigen was significantly higher in patients than controls. EBV reactivation may be important in the pathogenesis of NDPH. Alternatively, patients with NDPH may be unusually prone to EBV reactivation. PMID- 2880217 TI - Antibody to human T-lymphotropic virus type 1 in West-Indian-born UK residents with spastic paraparesis. AB - Of 13 West-Indian-born UK residents with spastic paraparesis of unknown cause, 11 were tested for serum antibody to human T-cell lymphotropic virus type 1 and all were positive. Their magnetic resonance imaging scans were normal or showed only minor abnormalities in the brain, and the spinal cord was normal in the 5 investigated. Of 48 patients with multiple sclerosis, mainly caucasian, none had antibody to HTLV-1 in the blood. PMID- 2880219 TI - Alpha 1-antitrypsin deficiency and prenatal diagnosis. PMID- 2880218 TI - Effect of cyclosporin, previous third-party transfusion, and pregnancy on antibody development after donor-specific transfusion before renal transplantation. AB - Non-cytotoxic and cytotoxic antibodies were sought after donor-specific transfusion (DST) in 12 potential renal transplant recipients given concomitant cyclosporin therapy and 13 given DST alone. Non-cytotoxic antibodies, which have been shown to develop after third-party transfusion and to be associated with successful transplantation, developed after DST whether or not cyclosporin was given. Donor and panel reactive lymphocytotoxic antibodies developed relatively infrequently after DST with or without cyclosporin. Donor-specific sensitisation occurred only in patients who were multiparous or had over 10 third-party transfusions. Non-cytotoxic Fc-receptor-blocking antibodies may play a part in the improved survival of one-haplotype-mismatched transplants pretreated with DST. PMID- 2880220 TI - Epilepsy--la belle indifference? PMID- 2880222 TI - Total ischaemic burden. PMID- 2880221 TI - Doubts about the value of maintenance lithium. PMID- 2880223 TI - The dominance of salt in manufactured food in the sodium intake of affluent societies. AB - Statistical analyses suggest that 25-50% of the salt intake of Western populations is derived from the discretionary use of cooking and table salt. Yet direct estimates of discretionary salt use by a lithium technique show that in one community in Britain this source contributed only 15% to total intake. The estimates of discretionary salt use in Finland, the United States, and Britain have been exaggerated because salt losses in cooking water were not considered. Only about a quarter of cooking salt actually enters the consumed food; allowance for this in statistical calculations makes data on dietary intake similar to those assessed from urinary sodium excretion. Daily salt intake in Britain averages about 10.7 g for adult men and 8.0 g for women, figures similar to those from countries in northern Europe. The natural salt content of food provides about 10% intake, the remaining 75% being derived from salt added by manufacturers; drinking water provides a negligible amount. Any programme for reducing the salt consumption of a population should therefore concentrate primarily on a reduction in the salt used during food processing. PMID- 2880224 TI - Which treatment for childhood acute lymphoblastic leukaemia in second remission? AB - The best therapy for children with acute lymphoblastic leukaemia (ALL) who have an initial bone marrow relapse and subsequently achieve second remission is controversial. Some findings suggest that bone marrow transplantation (BMT) is better than chemotherapy whereas others do not. An analysis of 871 children treated by BMT or chemotherapy showed that outcome was correlated with risk factors at diagnosis and with length of first remission. BMT seemed superior in patients who relapsed within 18 months of first remission while on maintenance chemotherapy. BMT was not demonstrably superior in patients who relapsed more than 18 months after first remission. The choice of treatment in childhood ALL must be based on prognostic variables at diagnosis and on the circumstances of the relapse. PMID- 2880225 TI - Appraisal of intradermal immunisation against hepatitis B. PMID- 2880226 TI - Immunosuppression in the treatment of insulin-dependent (type 1) diabetes. PMID- 2880227 TI - Rett's syndrome: a variant of Heller's dementia? PMID- 2880228 TI - Prenatal diagnosis of medium-chain acyl-CoA dehydrogenase deficiency in family with sudden infant death. PMID- 2880229 TI - Detection of Haemophilus influenzae with monoclonal antibody. PMID- 2880230 TI - Occult blood and faecal leucocyte tests in acute infectious diarrhoea in children. PMID- 2880231 TI - Rhabdomyolysis in doxylamine overdose. PMID- 2880232 TI - Lyme arthritis. PMID- 2880233 TI - Methysergide and retroperitoneal fibrosis. PMID- 2880234 TI - Prognosis of drug-induced Parkinson's disease. PMID- 2880235 TI - Tetrahydroaminoacridine and Alzheimer's disease. PMID- 2880236 TI - Place of aspiration cytology and the acute abdomen. PMID- 2880237 TI - Interference in commercial assays for thyrotropin. PMID- 2880238 TI - AIDS in a child without antibody to HIV. PMID- 2880239 TI - Health professionals' attitudes to AIDS and occupational risk. PMID- 2880240 TI - Decline of antibody reactivity to HIV core protein secondary to increased production of HIV antigen. PMID- 2880241 TI - Male contraception involving testosterone supplementation: possible increased risks of prostate cancer? PMID- 2880243 TI - Medical services in Gaza. PMID- 2880242 TI - Detection of factor VIII and IX inhibitors after first exposure to heat-treated concentrates. PMID- 2880244 TI - Medicines control in Switzerland. PMID- 2880245 TI - Recruitment to inpatient trials of antidepressants. PMID- 2880246 TI - Medical devices and consumer protection. PMID- 2880247 TI - Mortality and morbidity of long-term haemodialysis. PMID- 2880248 TI - Butchers and prostate cancer. PMID- 2880249 TI - Hearing loss and vibration-induced white finger. PMID- 2880250 TI - Predicting relapse in stage I non-seminomatous germ cell tumours of the testis. PMID- 2880252 TI - Chloroquine and platelets. PMID- 2880251 TI - Assessment of possible drug-resistant Plasmodium falciparum in a pregnant traveller with sickle cell disease. PMID- 2880253 TI - Prevalence of amoebic antibody in population affected by epidemic non-A, non-B hepatitis. PMID- 2880254 TI - Treatment of systemic nocardiosis. PMID- 2880255 TI - Graft-versus-leukaemia activity associated with cytomegalovirus antibody positive bone marrow donors in acute myeloid leukaemia. PMID- 2880256 TI - Interpretation of creatinine clearance. PMID- 2880257 TI - [Management of injuries of the distal tibia and foot]. AB - The complex injury of the foot requires immediate decisions. At first the question of vital danger and amputation should be ruled out. The criteria for the conservation of the extremity will be shown. For the most severely injured, primary amputation is indicated, since all attempts of preservation in this group hardly survived. The two-step amputation is recommended: i.e. "Guillotine" amputation in the acute phase and muscle plastic stump formation in the regeneration phase. Important principles of treatment are: immediate anatomic reduction and retention of fractures and unstable joints, open wound treatment, delayed closure and reconstructive plastic intervention. A planned "second-look" operation is obligatory. PMID- 2880258 TI - [Use of the mammary artery in coronary revascularization]. AB - From August 1983 through December 1985 1088 patients underwent coronary surgery. 406 (37%) received a single or bilateral internal mammary artery (IMA) graft with single or sequential anastomoses. The youngest patient was 6 years old, the oldest 75, with a mean age of 55.7 years. A total of 672 IMA anastomoses was constructed. In addition 348 patients received 610 saphenous vein grafts. 83% of the IMA were anastomosed to the LAD and its branches, 12% to the circumflex and 5% to the right coronary artery. 4 patients (0.98%) died postoperatively, 402 survived and are free of angina. In our experience the IMA can be used routinely with low operative risk and good results. PMID- 2880259 TI - [Indications for immediate and delayed amputation in severe soft tissue and skeletal injuries of the distal tibia]. AB - Primary amputation of the lower extremity has become rare in the last years due to the advances in rigid fixation of the bone, plastic and microsurgical techniques and aseptic surgery. Primary amputation is indicated in the presence of non-reconstructable lesions of vessels and/or nerves, secondary amputations when vascular, neural or septic complications occur. PMID- 2880260 TI - [Macro- and microreplantations of the lower leg and foot]. AB - Amputations suitable for replantation in the distal lower leg and foot are seldom. There is no indication if shortening will exceed 5 cm or loss of sensitivity is to be expected. Forefood and toe replantations are to be seen predominantly under aesthetic points of view. Satisfactory results in 10 own cases could be achieved if indications for lower leg replantations were limited to guillotine-type amputations, children and some bilateral lesions. Polytrauma as a rule is not a good indication. PMID- 2880261 TI - [Therapeutic concepts in neurologic damage following severe soft tissue and bone injuries of the distal lower leg and foot]. AB - In less than 1% of the cases nervous lesions after severe lower leg lesions demand surgical treatment: Neurosurgical Clinic: 28 reconstructive interventions on the lower leg, however, 362 on the forearm in 15 years; Clinic of Accident Surgery: 264 severest lower leg- and foot-injuries, among them only two nervous lesions. The n. peronaeus is more frequently affected than the n. tibialis. Even if continuity of the nerve is maintained, endoneural bleeding and internal ruptures can lead to extensive axonal lesions. The kind of nervous lesion (neurapraxia, axonotmesia, neurotmesia) should be clarified during the first three months, if possible, since it determines the prognosis as well as the kind of operative treatment during the first six months. PMID- 2880262 TI - [Post-traumatic osteitis following severe soft tissue and skeletal injuries of the distal lower leg and foot]. AB - Complications after severe soft tissue- and skeletal injuries of the distal lower leg and foot are frequent. The incidence of infection is outlined on the basis of the AO-Documentation-Center in Berne. In case of infection, necrotic tissue must be eliminated and stability of the fracture has to be maintained. Cancellous bone grafts as well as microvascular plastics should only be considered in the presence of a well vascularized fracture-bed. The benefit of antibiotics and disinfectants and the interrelation between infection and allergy to implants are discussed. PMID- 2880263 TI - [Local reconstructive possibilities following infections of the lower leg and foot]. AB - Basic rule: slough removal, treatment of infection, closure of the defect. Already existing infection: antiseptic solutions, rarely or never antibiotics. Measurement of wound pH (pH 6-8). According to indications, split thickness skin graft, in large defects mesh-graft. Reverdin grafts only in poorly healing wounds. For preparation of defect closure, silicone foam is very effective. If bone is exposed, we still use cross leg flaps and myocutaneous flaps besides more modern methods of plastic surgery. Distant flaps, like tube flaps from the abdomen have only historical interest. PMID- 2880265 TI - [Free tissue transfer]. AB - The free flap transfer has his place in situations were regional flaps- especially pedicled muscle flaps--are not available. This is especially true for the medial and distal third of the lower limb. Another important indication is in infected situations, where we can put the muscle, for example from the free myocutaneous flaps in the infected bone area. At the sole of the foot and the heel we see a special indication, because we can restore by the free tissue transfer sensibility. This means in our opinion a good precaution for reulceration. By the use of a two-team approach the primary long operation time could be cut down up to two to four hours. By simplifying the whole procedure we also could achieve a high success rate of 93.5% in 345 cases which we operated since 1974. In the last two years we did not have any necroses in 94 cases. Therefore we think that nowadays the indication for free flap transfer in the soft tissue reconstruction at the lower extremity and the foot has to be widened. PMID- 2880264 TI - [Transposition plasty]. AB - Severe soft tissue and bone injuries are at the lower leg area a special problem for reconstruction. Only a limited number of local tissue transfer methods is available especially in the distal lower leg. Fasciocutaneous flaps, muscle transposition and myocutaneous flaps are available to solve some of the problems. The indication, validity and local topographical use is discussed, early and aggressive debridement and early covering of soft tissue defects with the appropriate flaps is the best way to avoid infection and more damage. PMID- 2880266 TI - [Indications for corrective operations for maintaining function in post-traumatic deformities of the distal lower leg and foot]. AB - Reconstruction surgery in posttraumatic deformities in the lower leg and the foot is indicated under different aspects: restoration of function, improvement of prognosis, improvement of function and melioration of physical appearance. Technically effective surgical means are available to date, such as: metaphyseal closing and opening wedge osteotomies, diaphyseal step-cut osteotomies, diaphyseal and metaphyseal displacement osteotomies, lengthening osteotomy, external fixation, revision of infections, joint revisions, scar revisions, nerve revisions, plastic skin operations. PMID- 2880267 TI - [Severe soft tissue and bone injuries of the distal lower leg and foot: indications for arthrodesis or joint replacement]. AB - The results of ankle joint arthroplasty are disencouraging. Replacement is only justified, when there is no infect or instability and axial deviations below 20%. After fusion in 80% release of pain, more than 50% unlimited walking and only 10% the severe walking restriction is seen. Therefore this treatment can be recommended in posttraumatic tarsal osteoarthritis. PMID- 2880268 TI - [Rehabilitation]. AB - When serious injuries of the soft tissue and bone of the distal crus are not totally cured, orthesis and walking-sticks may bring relief in rehabilitation. Defects after recovery seldom need to be treated by orthesis or orthopaedic shoes. In most cases orthopedic additives to normal shoes can compensate malposition of the bone or lost function of the joint. PMID- 2880269 TI - [Differences in the neuromuscular blockade of the larynx and thenar muscles following relaxation with vecuronium]. AB - To objectivate the clinical impression of different neuromuscular depression in the larynx- and limb-musculature, an attempt was made in 5 patients to quantify laryngeal muscle relaxation by electromyographic recordings of evoked responses from the vocalis muscle during endolaryngeal microsurgery. Mechanographic and evoked electromyographic recordings of the thenar muscles were obtained simultaneously. Nearly total suppression of evoked responses at the peripheral muscle site was observed after a bolus dose of either 60 micrograms/kg or 100 micrograms/kg of the nondepolarising muscle relaxant Vecuronium. However, the vocalis muscle was not blocked completely. The neuromuscular depression ranged from 61 to 92% depending on the dose. In no case was the recommended intubating dose (ED 95) of 60 micrograms/kg sufficient for complete relaxation of the vocalis muscle. The present results do not support that the extent and/or time course of intrinsic laryngeal muscle relaxation correlates with peripheral neuromuscular depression in a quantitative manner. The different degree of relaxation achieved by Vecuronium in the hand and larynx is probably due to their different content of acetylcholine receptors. PMID- 2880270 TI - Chagasic IgG modifies the activity of sarcolemmal ATPases through a beta adrenergic mechanism. AB - The effect of anti beta adrenoceptor IgG from chagasic sera upon Ca2+-ATPase and Na++K+-ATPase of myocardial membrane was studied. Chagasic IgG stimulated Ca2+ ATPase and inhibited Na++K+-ATPase activities. Both enzymatic effects of the IgG could be prevented after beta adrenoceptor blockade or after the absorption of chagasic IgG with turkey red blood cells. Isoproterenol acted similarly. These results provide information concerning to the biochemical mechanism, by which an antibody, known to activate adenylate cyclase system coupled to cardiac beta adrenoceptor, produces stimulation of myocardial contractility. PMID- 2880271 TI - Hepatic clearance of somatostatin and gastrin-releasing peptide. AB - In order to examine hepatic clearance of gastrointestinal regulatory peptides, rat livers were perfused in situ, and radiolabelled somatostatin (S-14, S-28), gastrin-releasing peptide (GRP-14, GRP-27), and vasoactive intestinal peptide (VIP) were injected into the portal vein and hepatic venous effluent was collected. S-14 and S-28 were not affected significantly by hepatic transit: 91.6 +/- 2.8% (SEM) of S-14 and 95.9 +/- 2.2% of S-28 were recovered, and neither peptide was degraded by hepatic transit, as determined by immunoprecipitation and gel chromatography. GRP-14 and GRP-27 were also not affected by hepatic transit: 91.5 +/- 1.6% of GRP-14 and 94.4 +/- 2.4% of GRP-27 were recovered intact. In contrast, when radiolabelled VIP was infused into the portal vein, 56.7 +/- 7.4% of injected labelled VIP appeared in the hepatic venous effluent, of which only 33.5 +/- 1.2% was intact peptide. Results of these studies indicate that enteric VIP released into the splanchnic/portal circulation is cleared by hepatic transit. However, somatostatin and GRP peptides appear to traverse the liver intact and could potentially produce systemic biological effects. PMID- 2880272 TI - Pharmacological studies of somatostatin and somatostatin-analogues: therapeutic advances and perspectives. AB - This article is aimed at reviewing and analyzing studies that are related to the possible therapeutic use of a potent and ubiquitously-distributed hormone--somato statin (SS-14), and its analogues. Administration of these substances has provided beneficial effects in treating acromegaly, gastro-intestinal hemorrhagic and hypersecretory disorders, acute pancreatitis, diabetes mellitus, and certain types of cancer. Further studies with SS-14-analogues might provide new therapies for treating certain life-threatening disorders of man. PMID- 2880273 TI - Calcitonin gene-related peptide stimulates rat gastric somatostatin release in vitro. AB - The influence of rat calcitonin gene-related peptide (rCGRP) on the secretion of gastric somatostatin and gastrin was studied in vitro using the isolated, vascularly perfused rat stomach preparation. rCGRP stimulated somatostatin secretion dose-dependently reaching 3-fold stimulation at 1 microM. The kinetics of somatostatin response were characterized by a sharp increase in the initial phase of rCGRP perfusion followed by sustained elevated levels. Gastrin secretion was moderately suppressed at 1 nM to 100 nM CGRP. Somatostatin responses to half maximal stimulation with 100 nM CGRP were not affected by concomitant perfusion of atropine, propranolol, and tetrodotoxin. It is concluded that increases in somatostatin release in response to CGRP are probably due to a direct effect on the gastric somatostatin-producing D-cell and may be important for the potent acid-inhibitory activity of CGRP. PMID- 2880275 TI - [Neuroleptic parkinsonism]. PMID- 2880274 TI - Neuromelanin: a role in MPTP-induced neurotoxicity. AB - Methylphenyltetrahydropyridine (MPTP) selectively destroys melanin-containing neurons in the substantia nigra of humans and other primates. Methylphenylpyridine (MPP+), an active metabolite of MPTP, which is accumulated intraneuronally by the catecholamine uptake system, binds with high affinity to neuromelanin. MPP+ bound intracellularly to neuromelanin may be released gradually, resulting in damage to the neurons of the substantia nigra. Chloroquine, a drug which blocks MPP+ binding to neuromelanin, can protect monkeys from MPTP neurotoxicity. PMID- 2880276 TI - [Biliary excretion of enzymes in rats]. PMID- 2880277 TI - Basal glucose homeostasis with and without fixed concentrations of glucagon and insulin. AB - The aim of this study was to investigate the extent to which the basal steady state could be maintained with fixed concentrations of glucagon and insulin. To this end, arterial plasma glucose concentrations and peripheral glucose uptake (using the forearm technique) were compared in healthy men (age 19 to 23 years) in the normal postabsorptive state and after suppression of endogenous pancreatic secretion. Two groups (A and B), each consisting of four men, were studied. In group A, the study comprised a control period (I) of 40 minutes followed by a test period (II) of 180 minutes during which normal pancreatic secretion was maintained throughout. In group B, the study comprised a control period (I) of 40 minutes, a stabilization period (II) of 120 minutes, and a test period (III) of 120 minutes. After the control period with normal pancreatic secretion, a new steady state with fixed hormone concentrations was established during the first 90 minutes of period II using simultaneous infusions of somatostatin (250 micrograms/h), insulin (0.15 mU/kg/min) and glucagon, the latter being adjusted to maintain a stable arterial glucose level similar to the preceding control concentration. Thereafter, without further adjustment of the glucagon infusion rate, observations were continued during period III to assess the maintenance of the steady state. In group A, the range of variation in arterial glucose concentrations during periods I and II was 4.0 +/- 0.9 and 6.5 +/- 1.3 mg/dL, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2880278 TI - Development of a method to determine autonomic nervous system function in the rat. AB - A noninvasive method to evaluate autonomic nervous system (ANS) function in animals is needed for studies of diabetic autonomic neuropathy. These studies modified the RR-variation test, used to test diabetic ANS function in humans, and applied it to rats. Permanent wire electrodes were implanted in the chest wall of a rat. ECG complexes were obtained by connecting the electrodes to leads going to an impedence pneumograph and high gain coupler. This information was then converted into square waves by a trigger unit and recorded on magnetic tape for subsequent analysis by computer. Recordings were at least 60 seconds long, of which 30 seconds was used for analysis. In order to establish autonomic influence, RR-variation was measured before and after application of pharmacologic agents. Directly decreasing parasympathetic tone with atropine (20 mg/kg, n = 6) increased heart rate (P less than 0.001) and decreased RR-variation (P less than 0.05). Directly decreasing beta adrenergic tone with propranolol (10 mg/kg, n = 7) decreased heart rate (P less than 0.01) but had no effect on RR variation (NS). Stimulation of the beta adrenergic receptors (isoproterenol, 0.1 mg/kg, n = 5) increased heart rate (P less than 0.01) but decreased RR-variation (P less than 0.01). Increasing parasympathetic tone reflexly with alpha-1 adrenergic receptor stimulation (phenylephrine, 1 mg/kg, n = 7) decreased heart rate (P less than 0.05) and increased RR-variation (P less than 0.025). The responses to phenylephrine could be blocked by parasympathetic blockade. Phentolamine (0.1 mg/kg, n = 7) caused an increase in heart rate (P less than 0.001) and a decrease in RR-variation (P less than 0.01). The responses to phentolamine could be blocked by beta adrenergic receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2880281 TI - Drugs for asthma. PMID- 2880280 TI - Cloning of the ARO3 gene of Saccharomyces cerevisiae and its regulation. AB - Regulation of the two isozymes of 3-deoxy-D-arabino-heptulosonate-7phosphate synthase (DAHP synthase; EC 4.1.2.15) encoded by the genes ARO3 and ARO4 of Saccharomyces cerevisiae was studied. Both genes were shown to respond equally well to the general control of amino acid biosynthesis. Strains with mutations in these two genes were obtained by selecting first for a single aro3 mutation and afterwards for a double aro3 aro4 mutation. Gene ARO3, coding for the phenylalanine-dependent isozyme of DAHP synthase was cloned on the 2 micron multicopy vector pJDB207 by complementation of mutation aro3-1 in yeast. The ARO3 gene, carried originally on a 9.6 kb BamHI fragment (plasmid pME541A), was subcloned on a 1.9 kb HindIII-XbaI fragment (plasmid pME543). A transcript of about 1.5 kb was shown to proceed from the HindIII towards the XbaI site. Expression from the 9.6 kb as well as from the 1.9 kb fragment was normal on a multicopy vector, since in both cases DAHP synthase levels of about 50-fold the wild-type level were observed. PMID- 2880282 TI - Famotidine (Pepcid). PMID- 2880279 TI - The ATP synthase subunit 9 gene of Aspergillus nidulans: sequence and transcription. AB - We have determined the nucleotide sequence of the Aspergillus nidulans nuclear gene oliC31, which encodes subunit 9 of mitochondrial ATP synthase. The open reading frame contains no introns and specifies a predicted protein of 143 amino acids comprising a pre-sequence of 62 residues and a mature protein of 81 residues. The amino acid homology with the equivalent Neurospora crassa protein is 50% for the pre-sequence and 80% for the mature protein. A comparison with this and other imported mitochondrial proteins has revealed conserved regions which may be important for transport or subsequent processing. Multiple transcription initiation and polyadenylation sites have been identified. The promoter region of the oliC31 gene is characterised by long pyrimidine-rich tracts preceding the transcription initiation sites. PMID- 2880283 TI - [Double-blind comparison of fixed combination preparations of a beta blocker and a diuretic and beta blocker, a diuretic and hydralazine in patients with coronary heart disease and arterial hypertension]. PMID- 2880284 TI - Comparison of agonist-induced changes in beta- and alpha 1-adrenergic receptors of DDT1 MF-2 cells. AB - Agonist-induced changes in beta- and alpha 1-adrenergic receptors (BARs and AARs) were compared in the DDT1 MF-2 smooth muscle cell line. During equilibrium competition binding assays with intact cells at 37 degrees, agonists induced conversion of both BARs and AARs from a native form with high affinity for agonists to a form with much lower affinity for agonists. The native high affinity form of both receptors could be detected either in short-time competition binding assays at 37 degrees or in equilibrium competition binding assays on ice. Conversion to the low affinity form was nearly complete for BARs, but only about half of the AARs were converted to the low affinity form. For BARs, the high affinity form of the receptor observed in short-time assays with intact cells was similar to that observed in membrane preparations, whereas for AARs this form exhibited much higher affinity than was seen in membrane assays. None of these changes were observed during competition binding assays with antagonists. Both short-time competition binding assays with hydrophilic competing ligands and sucrose density gradient centrifugation assays were consistent with the occurrence of agonist-induced internalization of BARs. These same assays for AARs were consistent with the presence of some AARs in an intracellular compartment in the native state, but no agonist-induced increases in intracellular AARs were detected. During more prolonged exposure (13 hr) to agonists, about 80% down-regulation of BARs occurred, whereas only about 20% down regulation of AARs was detected. These results may indicate that internalization and down-regulation are not involved in conversion of these receptors to the low affinity form observed in intact cell binding assays. PMID- 2880285 TI - Shallow agonist competition binding curves for beta-adrenergic receptors: the role of tight agonist binding. AB - The beta 2-adrenergic receptors of bovine trapezius muscle membranes demonstrate tight agonist binding as a result of the formation of complexes between agonists, receptors, and Ns. Preincubation of the membranes with (-)-isoproterenol (followed by washing) causes a time- and concentration-dependent decrease in the number of radioligand-binding sites to a plateau value of 41.5 +/- 4%. The affinity of the remaining sites for the radioligand (-)-[3H]dihydroalprenolol is unchanged. This decrease is stable under radioligand binding conditions but is readily reversed in the presence of GTP. The isoproterenol/(-) [3H]dihydroalprenolol competition binding curves are shallow. Such a phenomenon is usually interpreted in terms of two interconvertible affinity states of the receptor: the high affinity state reflecting the coupling of the agonist X receptor complex to Ns and the low affinity state not interacting with Ns. However, the competition curves undergo time-dependent shifts to the left. This apparent non-equilibrium can be explained by a model in which tight agonist binding to part of the receptor population is included. The usual computerized interpretation of the competition binding curves do not allow the correct evaluation of agonist binding parameters in the presence of tight agonist binding. PMID- 2880286 TI - Alpha 2-adrenergic receptor turnover in adipose tissue and kidney: irreversible blockade of alpha 2-adrenergic receptors by benextramine. AB - The recovery of post- and extrasynaptic alpha 2-adrenergic receptor-binding sites was studied in vivo in male golden hamsters after treatment with an irreversible alpha-adrenoceptor antagonist benextramine, a tetramine disulfide that possesses a high affinity for alpha 2-binding sites. The kidney alpha 2-adrenergic receptor number was measured with [3H]yohimbine, whereas [3H]clonidine was used for fat cell and brain membrane alpha 2-binding site identification. Benextramine treatment of fat cell, kidney, and brain membranes reduced or completely suppressed, in an irreversible manner, [3H] clonidine and [3H]yohimbine binding without modifying adenosine (A1-receptor) and beta-adrenergic receptor sites. This irreversible binding was also found 1 and 2 hr after intraperitoneal administration of benextramine to the hamsters. Although it bound irreversibly to peripheral and central alpha 2-adrenergic receptors on isolated membranes, benextramine was unable to cross the blood-brain barrier of the hamster at the concentrations used (10-20 mg/kg). After the irreversible blockade, alpha 2 binding sites reappeared in kidney and adipose tissue following a monoexponential time course. Recovery of binding sites was more rapid in kidney than in adipose tissue; the half-lives of the receptor were 31 and 46 hr, respectively in the tissues. The rates of receptor production were 1.5 and 1.8 fmol/mg of protein/hr in kidney and adipose tissue. Reappearance of alpha 2-binding sites was associated with a rapid recovery of function (antilipolytic potencies of alpha 2 agonists) in fat cells inasmuch as occupancy of 15% of [3H]clonidine-binding sites was sufficient to promote 40% inhibition of lipolysis. Benextramine is a useful tool to estimate turnover of alpha 2-adrenergic receptors under normal and pathological situations using the approach described in the present paper. PMID- 2880287 TI - Comparison of the effect of eleven beta-adrenoceptor blocking drugs in perturbing lipid membrane: an ESR spectroscopy study. AB - The perturbation effect of the beta-adrenoceptor blocking drugs atenolol, propranolol, practolol, oxprenolol, doberol, pronethanol, metipranolol, alprenolol, Ko-1124, pindolol, and exaprolol on rat brain lipid membrane was investigated by ESR spectroscopy using the spin probe method. Using stearic acids spin labeled at the 5th, 12th, and 16th positions, it was found that lipophilic drugs disorder the membrane and their effect is about 5-10 times higher at the 16th carbon membrane depth than at the 5th depth. Exaprolol induced nonlamellar phases in the bovine brain lipid membrane as detected by 31P NMR spectroscopy. The relative potencies of the drugs at 10 mmol/liter concentration to disorder the lipid membrane at the 16th carbon depth were in the order: exaprolol greater than alprenolol approximately equal to propranolol greater than metipranolol approximately equal to doberol greater than control sample greater than pindolol approximately equal to practolol approximately equal to atenolol. This order qualitatively corresponds with some of their nonspecific biological membrane activities but is not related to their beta-adrenoceptor blocking potencies. The inequality of the membrane perturbation propensities of the drugs indicates that they perturb the lipid membrane in a structure-dependent manner, i.e., that each induces a specific rather than a nonspecific membrane perturbation. PMID- 2880289 TI - The epidemiology of human retrovirus-associated illnesses. PMID- 2880288 TI - [Linear elastic compliance of orthodontic wires]. PMID- 2880290 TI - [Repression of the synthesis and allosteric inhibition of 3-deoxy-D arabinoheptulosonate-7-phosphate synthase in facultative methylotrophic bacterium Pseudomonas sp. M]. AB - The synthesis of 3-deoxy-D-arabinoheptulosonate-7-phosphate-synthase has been shown to be repressed by tyrosine and phenylalanine in the cells of facultative methylotrophic bacteria Pseudomonas sp. M. Activity of the enzyme is subjected to allosteric inhibition by tyrosine, tryptophane, anthranylate and phenylpyruvate. PMID- 2880291 TI - A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease. AB - To search for a genetic marker for type 2 Gaucher's disease (acute neuronopathic form), we compared the nucleotide sequence of a cloned glucocerebrosidase gene from a patient with Gaucher's disease with a normal gene. We found only a single base substitution (T----C) in exon X. This mutation results in the substitution of proline for leucine in position number 444 and produces a new cleavage site for the NciI restriction endonuclease. We analyzed NciI enzymatic digests of genomic DNA from 20 patients with type 1, 5 with type 2, and 11 with type 3 Gaucher's disease, and 29 normal controls for a restriction-fragment-length polymorphism (RFLP). Four of 5 patients with type 2 disease and all 11 with type 3 disease had at least one allele with the mutation. Two of 5 patients with type 2 disease and 7 of 11 with type 3 were homozygous for this mutation. Only 4 of 20 patients with type 1 Gaucher's disease had the mutant allele and were heterozygous for it. None of the 29 normal controls had the mutant allele. The high frequency of this mutation (444leucine----proline) in patients with neuronopathic Gaucher's disease, detectable by the NciI RFLP, may be of value in the identification of patients who will have the neurologic sequelae of Gaucher's disease. PMID- 2880292 TI - Psychotropic drug use and the risk of hip fracture. AB - To assess the risk of hip fracture associated with the use of four classes of psychotropic drugs, we performed a case-control study of 1021 patients with hip fractures and 5606 controls among elderly Medicaid enrollees. Persons treated with hypnotics-anxiolytics having short (less than or equal to 24 hours) elimination half-lives had no increased risk of hip fracture. By contrast, a significantly increased risk was associated with current use of hypnotics anxiolytics having long (greater than 24 hours) elimination half-lives (odds ratio, 1.8; 95 percent confidence interval, 1.3 to 2.4), tricyclic antidepressants (odds ratio, 1.9; 95 percent confidence interval, 1.3 to 2.8), and antipsychotics (odds ratio, 2.0; 95 percent confidence interval, 1.6 to 2.6). The risk increased in relation to the doses of drugs in these three classes. An analysis for possible confounding by dementia did not alter the results. Previous but noncurrent use of drugs in these classes conferred no increase in risk. Although a cause-and-effect relation was not proved, these data support the hypothesis that the sedative and autonomic effects of psychotropic drugs increase the risk of falling and fractures in elderly persons. The results suggest the need for studies of this association in other populations and for evaluation of newer psychotropic drugs with fewer undesirable sedative and autonomic effects. PMID- 2880293 TI - Carrier detection in X-linked agammaglobulinemia by analysis of X-chromosome inactivation. AB - We used a recently developed strategy to analyze patterns of X-chromosome inactivation in human cell populations in order to study female members of families with X-linked agammaglobulinemia--i.e., to detect the carrier state and to test the hypothesis that the disorder results from a defect intrinsic in the development of B cells. According to this strategy, recombinant-DNA probes simultaneously detect restriction-fragment-length polymorphisms and patterns of methylation of X-chromosome genes. Random X-inactivation patterns were observed in isolated peripheral-blood granulocytes, T lymphocytes, and B lymphocytes of women who were not carriers. In contrast, one of the two X chromosomes was preferentially active in the peripheral B cells, but not the T cells or granulocytes, of three carriers of the disorder. This observation strongly supports the hypothesis that X-linked agammaglobulinemia results from an intrinsic defect in B-cell development. Moreover, the analysis described here can be used for direct identification of carriers in families with this disease. PMID- 2880294 TI - Efficacy of amoxicillin with and without decongestant-antihistamine for otitis media with effusion in children. Results of a double-blind, randomized trial. AB - In a randomized, double-blind, placebo-controlled trial involving 518 infants and children who had otitis media with effusion ("secretory" otitis media), we evaluated the efficacy of a two-week course of amoxicillin (40 mg per kilogram of body weight per day) with and without a four-week course of an oral decongestant antihistamine combination. Among the 474 subjects who were evaluated at the four week end point, the rate of resolution of middle-ear effusion was twice as high in those treated with amoxicillin, either with or without the decongestant antihistamine, as in those who received placebo (P less than 0.001), but 69.8 percent of the amoxicillin-treated subjects still had effusion. Among both the amoxicillin-treated subjects and the placebo-treated subjects, resolution was more likely in those with initially unilateral effusion, in those who had had effusion for eight weeks or less, and in those without an upper respiratory tract infection at the four-week end point. Side effects were reported more often in subjects who received decongestant-antihistamine than in those who did not. Among the subjects without effusion at the four-week end point, recurrent effusion developed in approximately half those in both the amoxicillin and placebo groups during the subsequent three months. We conclude that in infants and children with otitis media with effusion, amoxicillin treatment increases to some extent the likelihood of resolution. PMID- 2880295 TI - New application for DNA polymorphism. PMID- 2880296 TI - Monosomy 7 in granulocytes and monocytes in myelodysplastic syndrome. AB - Monosomy for all or part of chromosome 7 in bone marrow mitoses of some patients with myelodysplastic syndrome or acute nonlymphocytic leukemia has been associated with a defect in granulocyte function. To study which blood-cell lineages are affected by the monosomy, we used chromosome 7-specific DNA probes in Southern blotting experiments on DNA derived from specific cell fractions isolated from the blood of five patients. As judged by the presence or absence of two different alleles for restriction-fragment-length polymorphisms, lymphocytes of all five patients were shown to have two different chromosomes 7. Granulocytes were affected by the chromosomal abnormality in four patients (No. 1, 2, 4, and 5) and unaffected in one (No. 3). Chemotaxis was normal in Patient 3 and impaired in Patients 4 and 5. Monocytes were affected by the monosomy in two of three patients (No. 2 and 3) and mainly unaffected in one (No. 1). Thus, the granulocytes and monocytes were affected differently in different patients. We conclude that mature blood cells are derived from abnormal progenitors and that there may be heterogeneity in the involvement of different cell lineages in different patients with myelodysplastic syndrome or acute nonlymphocytic leukemia. There is an association between DNA loss and functional impairment. PMID- 2880297 TI - Quisqualate receptors are specifically involved in cerebellar synaptic plasticity. AB - Long-term modification of transmission efficacy at synapses is the cellular basis of memory and learning. A special type of synaptic plasticity in the cerebellum was postulated theoretically, and has since been verified. Each cerebellar Purkinje cell (PC) receives two distinct excitatory inputs, one from parallel fibres (PFs) and the other from a climbing fibre (CF). When these two types of inputs are conjunctively activated, PF-PC transmission undergoes long-term depression (LTD). Accumulated evidence suggests that LTD plays a role in the motor learning processes of the cerebellum. At the molecular level, LTD appears to be caused by desensitization of receptor molecules in PC dendrites towards the PF neurotransmitter, presumably L-glutamate (Glu). Glu receptors are heterogeneous and can be divided into several subtypes. In this study, we compared the potency of several Glu agonists in inducing LTD and found a highly selective dependency of LTD on the quisqualate(QA)-selective subtype of Glu receptors. PMID- 2880298 TI - Woman's AIDS death in Japan produces shock waves. PMID- 2880299 TI - Dopamine enhances excitatory amino acid-gated conductances in cultured retinal horizontal cells. AB - In the teleost retina, cone horizontal cells receive extensive innervation from dopaminergic interplexiform cells, and possess dopamine receptors whose activation stimulates adenylate cyclase. Exogenously applied dopamine modifies several aspects of horizontal cell activity in the intact retina, including the responsiveness of these neurons to light and the strength of electrical coupling between them. We have used whole-cell voltage clamp methods to examine whether dopamine can alter the light-responsiveness of horizontal cells by changing their sensitivity to the neurotransmitter released by the photoreceptors. We report that dopamine and cyclic AMP, although having little direct effect on resting membrane conductance, greatly enhance ionic conductances gated by kainate, an agonist of the transmitter released by the photoreceptors, and by L-glutamate, the agent proposed to be the photoreceptor transmitter. Our results provide the first direct evidence for dopaminergic regulation of excitatory amino-acid neurotransmission in the vertebrate nervous system and suggest a possible mechanism to explain the reduction in the responsiveness of horizontal cells observed when retinas are treated with dopamine. PMID- 2880300 TI - A new type of glutamate receptor linked to inositol phospholipid metabolism. AB - Receptors for excitatory amino acids in the mammalian central nervous system are classified into three major subtypes, ones which prefer N-methyl-D-aspartate (NMDA), quisqualate (QA), or kainate (KA) as type agonists respectively. These receptors are considered to mediate fast postsynaptic potentials by activating ion channels directly (ionotropic type). Recently it was reported that exposure of mammalian brain cells to glutamate (Glu) or its analogues causes enhanced hydrolysis of inositol phospholipids, but it is not clear whether the enhanced hydrolysis is the cause or effect of physiological responses. Membrane depolarization or Ca2+ influx, which can result from Glu receptor activation, can induce enhanced hydrolysis of inositol phospholipids. We have characterized the functional properties of two types of excitatory amino-acid responses, those activated by QA (or Glu) and those activated by KA, induced in Xenopus oocytes injected with rat-brain messenger RNA. We report evidence for a new type of Glu receptor, which prefers QA as agonist, and which directly activates inositol phospholipid metabolism through interaction with GTP-binding regulatory proteins (Gi or Go), leading to the formation of inositol 1,4,5-trisphosphate (InsP3) and mobilization of intracellular Ca2+. This QA/Glu reaction is inhibited by islet activating protein (IAP, pertussis toxin), but was not blocked by Joro spider toxin (JSTX), a specific blocker of traditional ionotropic QA/Glu receptors. PMID- 2880301 TI - Pleiotropic loss of activation pathways in a T-cell receptor alpha-chain deletion variant of a cytolytic T-cell clone. AB - Untransformed T-cell clones maintained in culture are dependent on signals transmitted through their antigen receptors (Ti; alpha and beta chains associated with the CD3 molecules) for growth and effector function. For cytolytic T cells (CTL), Ti stimulation also activates the killing machinery and induces synthesis of gamma interferon (IFN-gamma) messenger RNA and IFN-gamma secretion. The Thy-1 molecule, expressed on all murine cells of the T-cell lineage, has been suggested to function in transmembrane signalling, based on the ability of some anti-Thy-1 monoclonal antibodies (mAb) to activate T cells. Recently, it was suggested that Thy-1 could function as a signal-transduction molecule when expressed in B-cell lymphomas after transfection of the gene, leading to speculation that the molecule was part of an activation pathway independent of the Ti/CD3 structures. Here we report the immunoselection of a variant CTL clone which has lost expression of mRNA for the alpha-chain of the Ti. The Ti- variant was defective in lectin-mediated activation whether measured by increase in intracytoplasmic Ca2+, CTL effector function or IFN-gamma synthesis. The variant, which expressed normal levels of Thy-1, was also unresponsive to Thy-1 mAb activation as measured by IFN-gamma secretion, whereas it responded to calcium ionophore plus phorbol ester. These results indicate that in a non-transformed, functional mature T cell, Thy-1 mediated signalling is not an alternative to, but might depend on elements associated with the Ti/CD3-mediated T-cell activation pathway. PMID- 2880302 TI - (+)-AJ 76 and (+)-UH 232: central stimulants acting as preferential dopamine autoreceptor antagonists. AB - The biochemical and behavioral effects of the putative dopamine autoreceptor antagonists cis-(+)-5-methoxy-1-methyl-2-(n-propylamino)tetralin, (+)-AJ 76 and cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, (+)-UH 232, were evaluated in various in vivo models in rats. Both compounds produced a marked elevation in brain dopamine synthesis and turnover with only slight effects on the synthesis and turnover of serotonin (5-HT) and noradrenaline being noted. (+) AJ 76 and (+)-UH 232 also failed to antagonize the decrease in cortical noradrenaline synthesis rate caused by the alpha 2 agonist clonidine. The apomorphine-induced decrease in dopamine synthesis rate in gamma-butyrolactone (GBL) treated animals was completely blocked by (+)-AJ 76 and (+)-UH 232 but not by d-amphetamine or methylphenidate. In activity experiments using habituated animals, (+)-AJ 76 and (+)-UH 232 produced locomotor stimulation and weak stereotypies and antagonized the sedative effects of low doses of apomorphine. Locomotor hyperactivity induced by apomorphine or the dopamine agonist DiPr-5,6 ADTN was antagonized by (+)-UH 232 and to a lesser degree by (+)-AJ 76. The locomotor hyperactivity produced by (+)-AJ 76, (+)-UH 232 and methylphenidate was completely prevented by reserpine pretreatment and partially blocked by the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (alpha-MT), whereas d amphetamine-induced hyperactivity was only antagonized by alpha-MT pretreatment. It is concluded that (+)-AJ 76 and (+)-UH 232 produce behavioral stimulation via a preferential antagonism on central dopamine autoreceptors, an action different from that of all known stimulants including apomorphine, d-amphetamine and methylphenidate. (+)-AJ 76 and (+)-UH 232 possess but weak antagonistic effects on postsynaptic dopamine receptors and only the latter compound is able to induce sedation in rats. PMID- 2880304 TI - [Depot neuroleptic agents]. PMID- 2880303 TI - Evidence for a receptor mediated action of norepinephrine distinct from alpha- and beta-adrenoceptors. AB - The mode of action of (-) norepinephrine (NE) and UK-14,304-18 has been investigated using the cholinergically-evoked 'twitch' response of the electrically stimulated guinea-pig ileum. St 587 and benextramine were employed as antagonists. St 587 acted as a competitive antagonist toward UK-14,304-18, yielding an apparent pA2 value of 7.3. In contrast, St 587 failed to act competitively toward NE. Similarly, benextramine (1 X 10(-5) mol/l) blocked the inhibitory responses to UK-14,304-18 but was considerably less active toward NE. Remaining responses to NE after benextramine were not antagonized by St 587, even at a concentration of 3 X 10(-5) mol/l. It is postulated that NE acts to inhibit the 'twitch' response be evoking two different receptor-mediated events: 1. agonism at the alpha 2-adrenoceptor and 2. agonism at a site which is distinct from the alpha- and beta-subtypes. In the concentrations studied, UK-14,304-18, St 587 and benextramine are postulated to lack affinity for the proposed site. The effect of NE and UK-14,304-18 was also investigated on the contractile responses to exogenously applied histamine. These experiments were done in the presence of muscarinic cholinergic and adrenoceptor blockade. NE inhibited responses to histamine but UK-14,304-18 was inactive. Furthermore, the inhibitory action of NE was stereoselective with the (-) form being 25 times more potent than the (+) enantiomer. These findings suggest the presence of a receptor site for NE which is distinct from cholinergic mechanisms and established alpha and beta-adrenoceptors. PMID- 2880305 TI - Effects of iontophoretic application of trimethyltin on spontaneous neuronal activity in mouse hippocampal slices. AB - Changes in spontaneous activity in various regions of mouse hippocampal slices were observed following iontophoretic application of trimethyltin (TMT). TMT (0.5 mM) dissolved in 0.15 M NaCl and ejected in 30 sec periods from four barrel micropipettes using anodal ejection currents (3-28 nA) produced dose dependent increases in the spontaneous activity of 67.6% of the 34 dentate gyrus cells tested. Seventy percent of the 25 CA3 cells tested displayed prolonged (30-200 sec) decreases in activity. The majority of CA1 and CA2 cells examined also displayed a decrease in firing rate. Repeated applications of TMT produced increased variability in spontaneous firing rates in all regions tested. When slices were maintained in a low Ca++, high Co++ perfusion fluid to inhibit synaptic activity, the TMT induced increase of dentate gyrus cell firing rate was not observed. The results demonstrate that direct application of TMT produces immediate changes in hippocampal cell activity that is specific for certain regions. Significant increases in firing rate were only observed in the dentate gyrus and these effects were calcium dependent. PMID- 2880306 TI - Effect of cholinergic antagonists on basal and osmotically stimulated vasopressin release in compartmentalized hypothalamo-neurohypophysial explants. AB - The effects of cholinergic antagonists on vasopressin (VP) release were studied in an organ-cultured, compartmentalized, rat hypothalamo-neurohypophysial system which allows selective application of stimuli to either hypothalamus or pituitary without disrupting axonal connections. Release of vasopressin from the neurohypophysis was measured by radioimmunoassay. Hexamethonium (10(-5) M) and atropine (5 X 10(-5) M) were tested both alone and in combination with hypothalamic osmotic stimulation (+ 15 mosm/kg H2O). In hypothalamus, neither hexamethonium nor atropine had any effect on basal VP release from pituitary. Hexamethonium, but not atropine, prevented the increase in VP release produced by increased osmolality of the hypothalamus side culture medium. In contrast, hexamethonium had no effect when applied to pituitary side, whereas atropine suppressed both basal and osmotically stimulated VP release. Atropine had no effect on basal or KCl-induced VP release in detached neural lobes. Acetylcholine (Ach) (10(-5) M) to pituitary plus simultaneous, hypothalamic stimulation (osmotic or 10(-5) M Ach) did not increase VP release above the hypothalamic stimulus alone. The results support a role for a hypothalamic excitatory nicotinic mechanism in osmoregulation. The presence of a muscarinic mechanism affecting VP release in pituitary was reconfirmed, but the data did not support the hypothesis that Ach stimulates VP release in pituitary by a presynaptic facilitatory mechanism. PMID- 2880308 TI - Hypothalamic involvement in the hyperglycemia and satiety actions of somatostatin in rats. AB - To determine whether the anorexic and the hyperglycemia actions of somatostatin were mediated through the hypothalamic nuclei, rats were infused with somatostatin and normal saline through previously implanted hypothalamic cannulae. Administration of somatostatin (0.5-1.5 microgram in 1.0 microliter) into the lateral hypothalamus, but not the ventromedial or the anterior hypothalamus, caused a reduction in food consumption without affecting relative water intake (or water-to-food ratio) in conscious rats in a freely moving state. On the other hand, administration of somatostatin into the lateral hypothalamus, but not the anterior or the ventromedial hypothalamus, caused an increase in blood glucose level in rats. This hyperglycemia was antagonized by vagotomy, but not by spinal transection or adrenalectomy. The data indicate that the lateral hypothalamus is the most sensitive site of the somatostatin-induced anorexia and the action of somatostatin on the lateral hypothalamus-vagus efferent activity is also a possible mechanism mediating hyperglycemia in rats. PMID- 2880307 TI - Thyroidectomy and central catecholamine neurons of the male rat. Evidence for the existence of an inhibitory dopaminergic mechanism in the external layer of the median eminence and for a facilitatory noradrenergic mechanism in the paraventricular hypothalamic nucleus regulating TSH secretion. AB - Using the Falck-Hillarp methodology in combination with quantitative microfluorimetry, catecholamine (CA) levels and utilization in discrete hypothalamic CA nerve terminal systems in the male rat have been analyzed 24 h, 1, 2 and 4 weeks following thyroidectomy as well as after T3 or T4 restitution therapy 4 weeks after thyroidectomy. By means of high pressure liquid chromatography (HPLC), dopamine (DA) and noradrenaline (NA) levels and utilization 4 weeks after thyroidectomy have been analyzed in various brain regions. Triiodothyronine treatment (10 micrograms/kg, s.c., twice daily during 10 days) of 4-week athyroidic rats increased serum T3 levels, but not T4 serum levels. Thyroxine treatment (36 micrograms/kg, s.c., twice daily during 10 days) of 4-week athyroidic rats increased serum T4 levels and the T3 levels were found to be even slightly higher than those found in normal animals. Triiodothyronine or T4 restitution therapy reversed the changes induced by thyroidectomy on the anterior pituitary hormones (TSH, prolactin and growth hormone) and corticosterone secretion. It is suggested that removal of thyroid hormones may be responsible for the changes in the anterior pituitary hormones and corticosterone secretions. In the quantitative microfluorimetrical analysis 24 h, 1, 2 and 4 weeks after thyroidectomy, decreases in DA levels and utilization and increases in NA levels and utilization were found in the lateral palisade zone (LPZ) of the median eminence and in the parvocellular and magnocellular parts of the paraventricular hypothalamic nucleus (PA), respectively. In addition, 1-,2- and 4 week decreases were found in DA levels and turnover in the medial palisade zone (MPZ) as well as in NA turnover in the dorsomedial hypothalamic nucleus (DM) and in the 'border zone' (BZ) between the medial and lateral hypothalamus ventral to the fornix. In the HPLC analysis it could be demonstrated that 4 weeks after thyroidectomy decreases in DA levels and utilization in the mediobasal hypothalamus and increases in DA levels as well as NA levels and utilization in the hypothalamus had developed. The T3 or T4 restitution therapies after 4 weeks of thyroidectomy counteracted the effects on CA levels and utilization in all hypothalamic CA nerve terminal systems except for the reduced NA utilization found in the DM following 4 weeks after thyroidectomy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2880309 TI - The computer as a stereotactic surgical instrument. AB - We have developed methodology and stereotactic software for an operating room computer and imaging system. Patients undergo preoperative CT, MR and DSA imaging with their heads fixed in a stereotactic headholder. Localization systems attach to the headholder during the studies to create reference marks for computer transformation of points and volumes into three-dimensional stereotactic space. At the operating room computer console, the surgeon selects target points, avascular trajectories and tumour boundaries for volume reconstruction. Surgical approaches are simulated and target coordinates calculated. During surgery, the computer interactively monitors the position of stereotactically directed surgical instruments in relationship to the resident database along any viewing angle and conveniently superimposes the multiple data sources. We have found this system useful to provide rapid data acquisition and retrieval, accurate target point calculations, lesion volume reconstructions, and a convenient ability to reformat data from multiple sources in a manner useful to the surgeon and beneficial to the patient. PMID- 2880310 TI - The effects of etomidate in the cat middle cerebral artery occlusion model of brain ischaemia. An experimental study. AB - The effects of etomidate on focal cerebral ischaemia following transorbital occlusion of the cat middle cerebral artery were investigated. Etomidate had no effect on CBF before or after onset of ischaemia by comparison with controls, but caused a greater fall in CBF in cats with high preocclusion or initial ischaemic CBF than in those in which CBF was lower. There were more sustained rises in Kp on SG. The established flow threshold for water accumulation was lost; more gyri with CBF above and fewer gyri with CBF below the flow threshold accumulated water. The relationship between mean occlusion CBF and in vitro GABA uptake was lost; uptakes from MG were lower and from SG and EG higher than expected. In the ischaemic penumbra there was a trend towards reduction in CBF, disruption of ion homeostasis and cerebral oedema formation, whilst in areas of lower flow there was some recovery of GABA uptake and less cerebral oedema following administration of etomidate. PMID- 2880311 TI - Initiation and propagation of lipid peroxidation in cerebral infarction models. Experimental studies. AB - The possibility that cerebral ischaemia or cerebral hypoxia may initiate a series of free radical reactions in brain lipid constituents was explored by measuring sequential changes in chemiluminescence (CL) and electron spin resonance (ESR) during hypoxia or ischaemia load. Brain hypoxia was induced by means of arterial hypoxaemia (PaO2 17-22 mmHg), normocapnia (PaCO2 28-38 mmHg) and normotension (MABP 100-140 mmHg). To obtain lowered PaO2, 4% O2-96% N2 mixed gas was used for artificial ventilation. Spin trapping technique was used in ESR measurement and applied to the detection of free radicals generated in the ischaemic brain homogenate of three-vessel occlusion rat model (global highly ischaemic model with basilar artery coagulation and bilateral carotid artery clipping). Chemiluminescence (CL) began to rise in hypoxic or ischaemic loading and indicates high amounts at an early period of post-hypoxic or ischaemic state. The CL spectroanalysis by wavelength showed five peaks at 480 nm, 520-530 nm, 570 nm, 620-640 nm and 680-700 nm in both hypoxic and ischaemic brain. ESR measurement revealed the PBN (phenyl-t-butyl nitrone) trapped radical, which has hyperfine splitting constants of AN = 16.2-16.5 G and AH beta = 3.6-3.8 G in ischaemia model. An analysis of sequential change of PBN adduct intensity shows a peak at 30 min of ischaemic loading and a marked increase in the recirculation period. Preservation of ATP and marked lactic acidosis were seen in the 5 min hypoxic loading, elsewhere depletion of ATP and marked lactic acidosis were seen in the 5 min, 30 min ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2880312 TI - Treatment of blow-out fracture. AB - Fifteen patients with blow-out fractures were treated in this series. Two patients were treated conservatively and the thirteen others were treated surgically with the transorbital approach. An infraorbital or medial orbital skin incision was made. The periosteum was dissected and entrapment of orbital fat tissue and muscle were resolved. The floor and/or medial wall were reinforced with tantalum mesh (Codman). The operative results were good in 12 patients and fair in one patient, who retained some diplopia. The tantalum mesh is easy to handle and strong enough to reinforce the orbital wall. It can be seen on plain skull film and makes little artifact on CT scan. This mesh is good material for repairing blow-out fractures. PMID- 2880313 TI - Total excision of spinal lipomas using CO2 laser at low power. Experimental and clinical observations. AB - Total excision of spinal lipomas (SL) is difficult because of the intimate adhesion between the fibro-adipose tissue and the neural structures. Radical surgery in SL can provoke nervous lesions; therefore many authors recommend only partial excision as a means of decompression. Nevertheless the role of traction or tethering of the spinal cord in all spinal disraphism, including SL, is known to be very important in determining the clinical picture. So partial removal of SL cannot be effective in releasing the tethered cord. The use of a CO2 laser at low power (3-5 W) permitted radical surgery without any neural damage and complications in 2 adult patients with large, not well capsulated SL. These patients were previously operated on by the same surgeon with conventional microsurgical techniques for partial excision. After CO2 laser surgery there was significant improvement of the clinical pictures, the follow-up being respectively 24 and 36 months. This clinical experience was performed after a CO2 laser had successfully been used in an experimental model in rats simulating a condition of SL. Using power of 3-5 W was not sufficient to attain an immediate vaporization, but the adipose tissue first changed into a transparent liquid across which it was possible to recognize the interfaces between the neural structures and the adipose tissue. PMID- 2880314 TI - Cerebrovascular reactivity to acetazolamide in carotid artery disease. Enhancement of side-to-side CBF asymmetry indicates critically reduced perfusion pressure. AB - Cerebral blood flow (CBF), measured with a mobile 10 detector unit and non invasive Xenon-133 technique, was investigated before and after cerebral vasodilation with acetazolamide (Diamox) in 78 patients prior to carotid endarterectomy. The change in side-to-side CBF asymmetry from baseline to Diamox study, the Diamox asymmetry enhancement, was compared with the intraoperatively measured cerebral perfusion pressures. Asymmetry enhancement exceeded the methodological variation in 14 patients, 13 of whom had a perfusion pressure below 65 mmHg. Insignificant asymmetry enhancement was found in 64 patients: 52 with unilateral and 12 with bilateral disease. Of these two and four patients, respectively, had perfusion pressures below 65 mmHg. Enhancement of CBF asymmetry following a potent cerebral vasodilator stimulus is a reliable predictor, in unilateral carotid artery disease, of critically reduced cerebral perfusion pressure. PMID- 2880315 TI - Measurement of cerebral blood flow by intravenous xenon-133 technique and a mobile system. Reproducibility using the Obrist model compared to total curve analysis. AB - The recent development of a mobile 10 detector unit, using i.v. Xenon-133 technique, has made it possible to perform repeated bedside measurements of cerebral blood flow (CBF). Test-retest studies were carried out in 38 atherosclerotic subjects, in order to evaluate the reproducibility of CBF level and side-to-side asymmetry. Data were analysed according to the Obrist model and the results compared with those obtained using a model correcting for the air passage artifact. Reproducibility was of the same order of magnitude as reported using stationary equipment. The side-to-side CBF asymmetry was considerably more reproducible than CBF level. Using a single detector instead of five regional values averaged as the hemispheric flow increased standard deviation of CBF level by 10-20%, while the variation in asymmetry was doubled. In optimal measuring conditions the two models revealed no significant differences, but in low flow situations the artifact model yielded significantly more stable results. The present apparatus, equipped with 3-5 detectors covering each hemisphere, offers the opportunity of performing serial CBF measurements in situations not otherwise feasible. PMID- 2880316 TI - Prevention of symptomatic vasospasm after SAH by constant venous infusion of nimodipine. AB - Sixty-one patients with SAH due to rupture of a cerebral aneurysm, classified in Grades I to IV according to Hunt and Hess, received a constant venous infusion of Nimodipine in a dose of 2mg/h for at least 14 days, followed by an oral administration of 60 mg/6 h for at least 4 days. Patients admitted after the 6th day of SAH, patients with SAH but without aneurysm on the angiogram and patients in Grade V were excluded. Mortality in 30 patients of Grades I-II was 3.3%, in 31 patients of Grades III-IV 42%. In the latter group 1 patient died due to cerebral vasospasm. Transient vasospasm occurred in 2 patients of Grades I-II. Recovery was complete in both cases. Thus, incidence of cerebral vasospasm was 4.9%, the incidence of poor-outcome-vasospasm even only 1.6%. The syndrome of cerebral vasospasm seems to be more than only constriction of cerebral vessels. The deleterious effects of Ca2+ shift into vascular cells and into neural cells which causes irreversible damage are discussed. Early administration of a specific 'cerebral' calcium antagonist like Nimodipine after SAH will prevent the intracellular Ca2+ overloading, thus protecting the neural cells and preventing Ca2+-induced smooth-muscle contraction of cerebral vessels, which encourages ischaemic deficits after SAH. The preventive use of Nimodipine has markedly reduced the incidence of symptomatic vasospasm in our clinic. PMID- 2880317 TI - [H2 antagonists and the heart]. AB - The large scale use of drugs that block tissue histamine receptors (H1 and H2) creates the problem of possible side effects due to the inhibition of the physiological role of histamine on certain systems and/or the direct action of histamine receptor blockers. In the case of H2 antagonists the effects on the heart so far reported are few but are considered important since they suggest the presence of physiological mechanisms that are as yet imperfectly understood. The literature on the cardiac effects of cimetidine and ranitidine is reviewed and the extent of the effect of the two drugs is outlined on the basis of an analysis of cases presented, experimental protocols and the various hypotheses put forward. Apart from the speculative interest of the study, a possible predisposition to the cardiac effects of cimetidine and ranitidine is identified in patients with major basal pathologies or in critical conditions. On the basis of the large numbers treated worldwide and the sporadic reports of cardiac effects it is concluded that the drugs are very easily handled even from the viewpoint of cardiac effects. PMID- 2880318 TI - Excitatory amino acids and intracellular pH in motoneurons of the isolated frog spinal cord. AB - Double-barrelled pH-sensitive micro-electrodes were used to measure changes of intracellular and extracellular pH in and around motoneurons of the isolated frog spinal cord during application of excitatory amino acids. It was found that N methyl-D-aspartate, quisqualate and kainate produced a concentration-dependent intracellular acidification. Extracellularly, triphasic pH changes (acid-alkaline acid going pH transients) were observed during the action of these amino acids. The possible significance of such pH changes for the physiological and pathophysiological effects of excitatory amino acids are discussed. PMID- 2880319 TI - The effects of buspirone on sleep in the rat. AB - Buspirone is a novel anxiolytic compound that does not produce the sedation often associated with the use of benzodiazepines. The present study evaluated the effects of this anxiolytic on sleep in rats surgically prepared for long-term recordings. Buspirone, at a dose of 3 mg/kg i.p., produced a significant increase in total wake time (P less than 0.05) compared with drug-free controls. At a dose of 10 mg/kg i.p., rats displayed altered sleep patterns with the most significant effects observed in the first third of recording period. These animals displayed increased wakefulness (P less than 0.001), decreased non-REM sleep (P less than 0.001), and an obliteration of REM sleep (P less than 0.02). These data support the suggestion that the clinically useful anxiolytic buspirone, unlike the benzodiazepines, does not induce sleep. PMID- 2880320 TI - Monoamine oxidase activity in chick cerebral microvessels. AB - In chick brain microvessels, monoamine oxidase activity using catecholamines (dopamine and noradrenaline) and indoleamines (serotonin and tryptamine) as substrates was higher than that measured in synaptosomes and free mitochondria. In contrast, phenylalkyamines such as tyramine and 2-phenylethylamine were more deaminated in free mitochondria and synaptosomes than in microvessels. These results suggest that the activity of monoamine oxidase towards neurotransmitter amines in microvessels should be considered as a site of inactivation of these neurotransmitters in the chick brain parenchyma. PMID- 2880321 TI - 1-Methyl-4-phenylpyridinium (MPP+) but not 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) selectively destroys dopaminergic neurons in cultures of dissociated rat mesencephalic neurons. AB - Dopaminergic neurons were studied in cultures of dissociated cells from the ventral mesencephalon of fetal rat embryos (gestational day E15-16). After a week of growth, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4 phenylpyridinium (MPP+) was added to the growth medium for 24 h. Dopaminergic neurons were then visualized with tyrosine hydroxylase (TH) immunocytochemistry or catecholamine (CA) cytofluorescence. Concentrations of MPTP in the range of 10 to 100 microM obliterated CA fluorescence without affecting the number of TH positive neurons. At concentrations greater than 100 microM, MPTP decreased the number of TH-positive neurons as well as the number of all other cell types. MPP+ (0.1-10.0 microM) produced a decrease in the number of TH-positive neurons without decreasing the total number of all cell types. The findings indicate that MPP+ but not MPTP is able to selectively destroy rat dopaminergic neurons in our cultures. The selective toxicity of MPP+ for dopaminergic neurons was partially prevented by pretreatment and co-incubation with mazindol (a selective inhibitor of dopamine uptake) but not by desipramine or deprenil, in confirmation of the notion that MPP+ enters dopaminergic neurons by the specific uptake mechanism for dopamine. PMID- 2880323 TI - Australian Neuroscience Proceedings. Abstracts of the seventh meeting of the Australian Neuroscience Society. Newcastle, Australia, February 3-5, 1987. PMID- 2880322 TI - 2-Oxo-[14C]glutarate is taken up by glutamatergic nerve terminals in the rat striatum. AB - High affinity uptake of [14C]glutamate into rat striatal synaptosomes was reduced by 33% after bilateral cortical ablation. The lesion had no effect on striatal [14C]GABA uptake, but reduced 2-oxo-[14C]glutarate uptake by 67%. The results demonstrate the existence of a high-affinity uptake site for 2-oxoglutarate on glutamatergic nerve terminals and support the contention that this Krebs cycle intermediate may be used to replenish the neuronal pool of neurotransmitter glutamate. 2-Oxo-[14C]glutarate uptake may serve as a selective marker for glutamatergic neurones. PMID- 2880324 TI - Differentiation of the Ca2+-stimulated binding from the Cl- -dependent binding of [3H]glutamate in synaptic membranes from rat brain. AB - The effect of Ca2+ as well as Cl- ions on [3H]glutamate (Glu) binding was re examined using rat brain synaptic membranes frozen at -80 degrees C in 0.32 M sucrose. The inclusion of 20 mM ammonium chloride or 20 mM ammonium chloride plus 2.5 mM calcium acetate disclosed the Cl- -dependent binding or Ca2+-stimulated binding even at 2 min after the initiation of incubation at 30 degrees C and each binding reached a plateau within 30 min. In contrast, the binding reached its maximal value within 10 min followed by a progressive decline up to 60 min in the presence of 100 mM sodium acetate. Scatchard analysis revealed that Cl- as well as Cl-/Ca2+ ions invariably caused a significant increment of the number of binding sites without altering their affinity, whereas Na+ ions induced a prominent increment of the density of binding sites with a concomitant lowering of their affinity. DL-2-Amino-4-phosphonobutyric acid selectively abolished the Cl- -dependent and Ca2+-stimulated bindings without significantly affecting the basal or Na+-dependent binding. Quisqualic acid induced a profound inhibition of both Cl- -dependent and Ca2+-stimulated bindings, to a significantly greater extent than that of the basal and Na+-dependent bindings. D-Aspartic acid exhibited a potent inhibition of the Na+-dependent binding with a significantly less potent displacement of the basal, Cl- -dependent and Ca2+-stimulated bindings. An inhibitor of anion transport, 4,4'-diisothiocyanatostilbene-2,2' disulfonic acid (DIDS), not only eliminated the Cl- -dependent binding, but also completely abolished the Ca2+-stimulated binding. Scatchard analysis revealed that DIDS (0.1 mM) prevented the Cl- - and Cl-/Ca2+-induced increment of the density of binding sites with no significant change of their affinity. Pretreatment of the membranes with hydrophilic SH-reactive agents such as N ethylmaleimide and 5,5'-dithiobis-(2-nitrobenzoic acid) invariably resulted in a more sensitive inhibition of the Ca2+-stimulated binding than that of the Cl- dependent binding, while hydrophobic reagent p-chloromercuribenzoic acid produced a similarly potent elimination of the Cl- -dependent and Ca2+-stimulated bindings. Calcium-stimulated binding was also found to be sensitively diminished by dithiothreitol and dithioerythritol as compared with the Cl- -dependent binding. In vitro addition of L-ascorbic acid (10(-6)-10(-3) M) attenuated the Ca2+-stimulated binding to a significantly greater extent than the inhibition of the Cl- -dependent binding.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2880325 TI - A protocol for the diagnosis and treatment of extrapyramidal symptoms of neuroleptic drugs. AB - The incidence of extrapyramidal symptoms in persons taking neuroleptic medications is reported in a majority of patients and can be a contributing factor to non-compliance with prescribed regimens. This protocol was developed to assist the nurse practitioner in assessing and treating these symptoms as well as aiding in determining when to consult and/or refer a patient for further treatment and follow-up. PMID- 2880327 TI - The efficacy of sulphasalazine. PMID- 2880328 TI - Prescriptions, OTC medications affect worker performance, safety. PMID- 2880326 TI - Neurotransmitters, anxiety and benzodiazepines: a behavioral review. AB - The possible involvement of serotonin, GABA and opioid peptides in anxiety and in the mechanism of action of benzodiazepine tranquilizers have recently been the subjects of intensive biochemical, neurophysiological and behavioral research. The present review examines the behavioral evidence, viewing anxiety and benzodiazepine action as far as possible separately. Four behavioral paradigms of experimental anxiety or "conflict behaviors" are described and assessed for soundness with some practical considerations. The functional significance and pharmacology of benzodiazepine receptors are discussed, and the cases for a number of putative endogenous ligands are examined. Conflict behavior is attenuated by drugs which reduce functional serotonin activity and enhanced by serotonin agonists, but there is little evidence to implicate serotonin in benzodiazepine action. GABA antagonists both intensify conflict and reduce benzodiazepine effects, but evidence of the reverse effects with GABA agonists is more equivocal. The interpretation of behavioral effects of opiate agonists and antagonists and their interactions with benzodiazepines is hindered by their actions on motivational systems other than anxiety, and evidence for an important role of opioid peptides is only suggestive. Some promising lines for future research are indicated. PMID- 2880329 TI - [Abscesses of the anterior cranial fossa from data of the Otolaryngological Clinic, Medical Academy, in Poznan 1964-1984]. PMID- 2880330 TI - Active suppression of interleukin 2 secretion in mice infected with Trypanosoma brucei AnTat 1.1.E. AB - Impairment of T cell proliferation in mice infected with the pleomorphic Trypanosoma brucei AnTat 1.1 E clone was found not to be related to a depletion of T cells or to an absence of functional accessory cells, but rather to an active suppression of interleukin 2 (IL-2) production. Lymph node cells derived from infected mice failed to produce IL-2 following Con A stimulation, whereas an exogenous supply of recombinant IL-2 could restore the impairment of the mitogen (Con A)-induced proliferative responses. Furthermore, lymph node cells derived from infected mice suppressed both secondary T-cell proliferative responses and IL-2 secretion, indicating that the trypanosome-induced suppression is mediated by a suppressive cell which interferes at the level of IL-2 secretion. PMID- 2880331 TI - Protection of mice against intestinal amoebiasis with BCG, Corynebacterium parvum and Listeria monocytogenes. AB - Treatment with Corynebacterium parvum or BCG, or infection with live Listeria monocytogenes was found to protect mice against subsequent infection with Entamoeba histolytica. Complete protection was obtained in mice treated with 10(7) (colony forming units) of BCG but not with 10(5). Partial protection was achieved with 10(6) of BCG. These data provide evidence that non-specific immunity plays an important role in the host defense against amoebic infection. PMID- 2880332 TI - Biological factors in prepubertal major depression. PMID- 2880333 TI - [Comparative effects of somatostatin and ranitidine on gastric function in children with hyperchlorhydria]. PMID- 2880334 TI - Mood, memory, and motor performance and the severity of tardive dyskinesia. AB - This study tested the hypothesis that the features of tardive dyskinesia were associated with motor slowing, memory impairment, and depressive apathy all of which are considered to characterize the so-called subcortical dementias. In a sample of 48 psychiatric patients all fulfilling research criteria for tardive dyskinesia and without other signs of organic illness age-independent correlations were observed between severity of orofacial dyskinesia and measures of memory, motor performance and mood providing some empirical support for the hypothesis. PMID- 2880335 TI - [Collection of circulating stem cells during remission after chemotherapy in acute leukemia]. AB - The level of circulating myeloid progenitor cells (CFU-G), considered to be a good index of the quantity of circulating hemopoietic stem cells, was measured in the peripheral blood of 5 patients with acute leukemia as they entered first remission. High levels of circulating CFU-G were found in 4 of these 5 patients, depending on the intensity and the number of courses of induction chemotherapy. Repeated cytaphereses were done on 3 of these patients in order to collect and to cryopreserve circulating stem cells, to be used later for autologous transplantation. We propose a model which calculates the number of cytaphereses sufficient to obtain a level of 10(5) CFU-G/kg of weight, considered necessary to achieve a good hemopoietic reconstitution after transplantation. PMID- 2880338 TI - A standard for dorsal-plantar and lateral radiographic projections of the feet. AB - Several attempts have been made to persuade physicians to establish standardized projections of foot radiographs. However, standards have not been widely accepted. Further advancement toward quantification of deformity and surgical criteria is delayed due to a lack of universally accepted technique. Procedures for obtaining two precise projections of the foot are described. PMID- 2880337 TI - Linkage of tyrosine hydroxylase to four other markers on the short arm of chromosome 11. AB - Tyrosine hydroxylase is the rate-limiting enzyme in catecholamine synthesis; the gene has previously been cloned and localised to the short arm of chromosome 11. Because of the interest in tyrosine hydroxylase as a candidate gene for manic depressive psychosis and other affective disorders, we carried out family studies to determine the linkage of tyrosine hydroxylase with insulin, beta-globin, D11S12 and Harvey-ras 1, members of a linkage group which has previously been localised to 11p. Using DNA from the Centre d'Etude du Polymorphisme Humain (CEPH) and from two large British pedigrees, we show that tyrosine hydroxylase is closely linked to these four loci (z = 7.36, theta = 0.04 for linkage to insulin) and suggest a gene order based on multipoint mapping. PMID- 2880336 TI - The maintenance of methylation-free islands in transgenic mice. AB - The Thy-1 gene is expressed in a tissue- and stage-specific pattern and has a typical 1.6kb methylation-free island (MFI) covering about 600bp upstream and downstream of the two alternative first exons. By microinjection of a mouse Thy 1.1/human Thy-1 gene into fertilized eggs, we were able to show that the MFI is restored in the transgenic mice. The flanking sequence became methylated, but the MFI remains unmethylated in all tissues of transgenic mice at different developmental stages tested, irrespective of the site of expression of the gene. There is one exception, in extra-embryonal tissues of 14.5 day embryos a small percentage of the islands were methylated. We conclude that maintenance of the MFI is regulated by cis-acting sequences present within the gene, and indicates that the unmethylated state of the islands is consistent with a necessary but not sufficient condition for expression of the gene. PMID- 2880339 TI - Reconstruction of soft tissue injuries of the foot and ankle with microsurgical techniques. AB - Microsurgical reconstruction for injuries of the foot and ankle includes, in addition to repair of small nerves, vessels, and tendons, coverage of soft tissue defects. Local transpositional and island pedicle flaps are ideal when available and adequate. The choice of free vascularized flaps is based on its potential durability, contour, bulk, and appearance. Thin cutaneous flaps, fascial flaps, and muscle flaps covered with split thickness skin grafts are appropriate in specific areas. Neurosensory flaps and methods of reinnervation may have a place in extensively denervated feet. Good postoperative pedorthic care aids in the final outcome. PMID- 2880340 TI - Allergic rhinitis. A useful guide to diagnosis and treatment. AB - Patients presenting with typical signs and symptoms of allergic rhinitis may respond to avoidance of allergens and to medications for symptomatic relief. Treatment may include antihistamines, decongestants, cromolyn sodium, and/or topical nasal steroids. Patients whose symptoms are refractory to these therapeutic measures should be referred to an allergist for further evaluation and consideration for possible allergen immunotherapy. PMID- 2880342 TI - Prenatal diagnosis of classical phenylketonuria by linked restriction fragment length polymorphism analysis. AB - Since the isolation of a recombinant containing a cDNA sequence for human phenylalanine hydroxylase (hPH) (Woo et al., 1983; Speer et al., 1986) prenatal diagnosis by linked restriction fragment length polymorphism (RFLPs) has become possible for families in which phenylketonuria (PKU) occurs (Lidsky et al., 1985a). We describe here the application of a Hind III three-allele RFLP in a single family, which allowed the prenatal diagnosis of an affected fetus. PMID- 2880341 TI - Comparison of the effects of atenolol, sotalol and labetalol on muscle blood flow in man. AB - A double-blind study of the effect of three beta-adrenoceptor blocking drugs (beta-blockers) on exercise muscle blood flow (MBF) in 14 normotensive volunteers was carried out. MBF was measured by the xenon-133 clearance technique. MBF was not altered by placebo, sotalol or labetalol. Atenolol significantly reduced MBF compared with placebo, sotalol and labetalol. We conclude that sotalol and labetalol may be more useful than conventional beta-blockers for treatment of hypertension or angina in association with peripheral vascular disease. PMID- 2880343 TI - Purification of human erythrocyte transglutaminase by immunoaffinity chromatography. AB - Human erythrocyte transglutaminase was purified using a reusable immunoaffinity column prepared from a monoclonal antibody described previously (Birckbichler et al., Hybridoma, 4, 179-186, 1985). The purified TGase was catalytically active and exhibited a single band of apparent Mr = 85,000 on SDS-PAGE and Western blotting. The amino acid composition of the enzyme was determined. The amino terminus was blocked, and the carboxy-terminal residue appeared to be isoleucine. PMID- 2880344 TI - [Biliary fistula: possible value of somatostatin]. PMID- 2880345 TI - [Salazosulfapyridine responsible of eosinophilic pneumonia]. PMID- 2880346 TI - The nature of neuroendocrine abnormalities in depression: a controversial issue in contemporary psychiatry. AB - Neuroendocrine abnormalities in depression have been regarded, by many authors, as relatively specific markers of nosological subtypes of the disorder, e.g. primary vs. secondary, endogenous vs. non-endogenous or unipolar vs. bipolar depression. They should reflect the same changes in central neurotransmitters (e.g. noradrenergic insufficiency and/or cholinergic hyperactivity) that were hypothesized as the cause of clinical symptoms. This view is challenged on the basis of our own neuroendocrine investigations in 317 psychiatric patients and 103 normal controls. According to these studies the abnormalities are nosologically rather unspecific. They are induced by a large variety of factors, e.g. emotional stress associated with the clinical symptomatology, weight loss due to malnutrition as a consequence of reduced appetite, medication and drug withdrawal. Stress-induced hypercortisolism appears to be the most common abnormality that may trigger other neuroendocrine dysfunctions, such as a blunted TSH response to TRH. Differences in neuroendocrine abnormalities of depressives are probably due to variations in the manifold factors influencing the hormonal axes involved, to temporal changes in hormonal patterns (e.g. one abnormality triggering another) and to individual differences in the basic activity and the responsiveness of the various axes. PMID- 2880348 TI - On the spatial spread of rabies among foxes. AB - We present a simple model for the spatial spread of rabies among foxes and use it to quantify its progress in England if rabies were introduced. The model is based on the known ecology of fox behaviour and on the assumption that the main vector for the spread of the disease is the rabid fox. Known data and facts are used to determine real parameter values involved in the model. We calculate the speed of propagation of the epizootic front, the threshold for the existence of an epidemic, the period and distance apart of the subsequent cyclical epidemics which follow the main front, and finally we quantify a means for control of the spatial spread of the disease. By way of illustration we use the model to determine the progress of rabies up through the southern part of England if it were introduced near Southampton. Estimates for the current fox density in England were used in the simulations. These suggest that the disease would reach Manchester within about 3.5 years, moving at speeds as high as 100 km per year in the central region. The model further indicates that although it might seem that the disease had disappeared after the wave had passed it would reappear in the south of England after just over 6 years and at periodic times after that. We consider the possibility of stopping the spread of the disease by creating a rabies 'break' ahead of the front through vaccination to reduce the population to a level below the threshold for an epidemic to exist. Based on parameter values relevant to England, we estimate its minimum width to be about 15 km. The model suggests that vaccination has considerable advantages over severe culling. PMID- 2880349 TI - Hormonal regulation of glutamine synthetase in the retina: role of cell interactions. PMID- 2880347 TI - Activation of growth factor secretion in tumorigenic states of breast cancer induced by 17 beta-estradiol or v-Ha-ras oncogene. AB - The MCF-7 human breast cancer cell line responds to estrogen stimulation in vitro by increased secretion of growth factors and proliferation and in vivo by tumor formation in the nude mouse. To test a possible role of growth factor secretion in expression of the tumorigenic phenotype, we stably transfected MCF-7 cells with the v-Ha-ras oncogene to produce the MCF-7ras cell line. The MCF-7ras cell line was tumorigenic in the absence of estrogens and secreted 3- to 5-fold elevated levels of a high molecular weight form of a type alpha transforming growth factor-like growth factor, type beta transforming growth factor, and insulin-like growth factor I. MCF-7ras cells, in contrast to MCF-7, were less sensitive to further growth stimulation by estrogen, type alpha transforming growth factor, and insulin-like growth factor I and showed little change in receptor levels for these hormones. Conditioned medium from MCF-7ras cells as well as two of its component growth factors (insulin-like growth factor I and type alpha transforming growth factor) replaced estrogen in stimulating MCF-7 colony formation in vitro. A coordinate increase in growth factor secretion by human breast cancer may contribute to its escape from estrogen dependence. PMID- 2880350 TI - Affinity for the dopamine D2 receptor predicts neuroleptic potency in decreasing the speed of an internal clock. AB - For each of five neuroleptics (chlorpromazine, haloperidol, pimozide, promazine, and spiroperidol), the dose required to produce a rightward horizontal shift of 15-20% for psychophysical bisection functions that relate the percentage of long responses to signal duration was determined in rats for two different signal ranges (2-8 sec and 4-16 sec). Affinity for the dopamine D2 receptor (from in vitro studies) predicted neuroleptic potency in producing the criterion shift of the timing functions, whereas affinity for other aminergic receptors (D1, D3, the alpha-noradrenergic receptor, S1, and S2) did not. The conclusion is that dopamine D2 receptors play a major role in determining the rate of temporal integration for time estimation. PMID- 2880351 TI - Stimulant-like effects of magnesium on aggression in mice. AB - The effects of magnesium excesses resulting from daily injections of magnesium chloride (MgCl2) were examined on offensive behavior in a resident-intruder situation. Male mice tested 5 min post-injection of 15 mg/kg or 30 mg/kg exhibited a significantly greater number of attacks and threats than saline controls; while in mice injected with 125 mg/kg threat and attack behaviors were decreased. No tolerance developed to this decrease which persisted throughout the 15 day injection period. Tolerance to the aggression enhancing effects developed in the 30 mg/kg group which returned to normal by Day 4 and in the 15 mg/kg group which returned to normal by Day 15. Two weeks following the last injection, all groups performed equally. When mice were tested prior to daily injections on Days 4, 8, and 15 in a second experiment, there were no MgCl2 dose differences in threat or attack behavior, thus there was no cumulative effect of MgCl2 on behavior. These data and our previous data showing that MgCl2 deficiencies reduce offensive aggression suggest an inverted U-shape function to magnesium's influence on behavior. Since aggression has been linked to the neurotransmitters dopamine, norepinephrine, and serotonin, and magnesium has been shown to be an important cofactor in the activity of these neurotransmitters, it is possible that the effects seen here are related to changes in one or more of these systems. PMID- 2880353 TI - Quantitative aspects of the ecology of biological invasions. PMID- 2880352 TI - Interactions of Tyr-MIF-1 at opiate receptor sites. AB - Binding of Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) to mu and delta opiate receptors was compared with other putative opiate antagonist peptides by displacement of iodinated ligands selective for mu (DAGO, FK33824, and morphiceptin) and delta (DPDPE) receptors. Tyr-MIF-1 and ACTH (1-24 and 1-39) inhibited binding of 125I DAGO with IC50's of about 1 microM. FMRF-NH2 was about an order of magnitude weaker while CCK-8 and MIF-1 failed to inhibit 50% of binding at concentrations up to 100 microM. Morphiceptin, Tyr-MIF-1, and ACTH were less potent but more efficacious than DAGO, FK33824, morphine, or naloxone in inhibiting the binding of 125I-morphiceptin. Tyr-MIF-1 appeared to have a more selective action at opiate receptors than ACTH; in contrast to their effects at 125I-DAGO-labeled sites, morphiceptin and Tyr-MIF-1 inhibited less than 50% of 125I-DPDPE binding at concentrations up to 10 and 50 microM, while ACTH 1-39 and 1-24 inhibited more than 80% of the binding at 2.5 and 5 microM, respectively. The results indicate that at relatively high concentrations Tyr-MIF-1, like ACTH, can affect binding to the opiate receptor, but unlike ACTH, binding of Tyr-MIF-1 appears relatively selective for the mu site. PMID- 2880354 TI - The invasion, persistence and spread of infectious diseases within animal and plant communities. AB - Recent theoretical and empirical studies of the population biology of infectious diseases have helped to improve our understanding of the major factors that influence the three phases of a successful invasion, namely initial establishment, persistence in the longer term and spread to other host communities. Of central importance in all three phases is the magnitude of the basic reproductive rate or transmission potential of the parasite. The value of this parameter is determined by a variety of biological properties of the association between an individual parasite and its host and the interaction between their populations. The recent epidemic of acquired immunodeficiency syndrome (AIDS) in North America and Europe is employed to illustrate the factors that promote disease establishment and spread. The frequency distribution of the number of different sexual partners per unit of time within homosexual communities is shown to be of central importance with respect to future trends in the incidence of AIDS. Broader aspects of pathogen invasion are examined by reference to simple mathematical models of three species associations, which mirror parasite introduction into resident predator-prey, host-parasite and competitive interactions. Many outcomes are possible, depending on the values of the numerous parameters that influence multi-species population interactions. Pathogen invasion is shown to have far-reaching implications for the structure and stability of ecological communities. PMID- 2880355 TI - The establishment and spread of myxomatosis and its effect on rabbit populations. AB - The establishment of myxomatosis, the spread of the disease and its effects on rabbit populations in Australia and in Britain are briefly reviewed. Though the disease is endemic, with regular outbreaks in most rabbit populations, its effect is now much less dramatic than previously. Recent epidemiological studies have shown that the rate of spread of infection, the proportion of rabbits infected and the proportion dying from the disease are very much smaller than recorded in earlier outbreaks. The reasons for these changes are discussed, and the epidemiology of the disease in Britain is compared with that in Australia. PMID- 2880356 TI - [Remarks on the classification status of endogenous psychoses]. PMID- 2880357 TI - [Attempt at neurobiochemical confirmation of the Leonard classification of psychoses]. PMID- 2880358 TI - [Effect of long-term neuroleptic medication on the course of phasic and remittent subclasses of endogenous psychoses]. PMID- 2880359 TI - The concept of noise. AB - "Noise" is a term we are using to describe a complex and distressing aspect of the bodily and cognitive experience of many very ill psychiatric patients. By "noise," we mean an internally experienced state of crowding and confusion created by a variety of stimuli, the quantity, intensity and unpredictability of which make it difficult for individuals so afflicted to tolerate and organize their experience. Attempts to do so may only add to confusion and psychotic phenomena. PMID- 2880360 TI - Neuroleptic bioavailability, psychosocial factors, and clinical status: a 1-year study of schizophrenic outpatients after dose reduction. AB - Serum neuroleptic levels, prolactin levels, and clinical state were assessed for 1 year in 29 schizophrenic outpatients whose clinically determined neuroleptic dose had been reduced by 50%. Fifty-five percent of the subjects remained stable. Neuroleptic dose did not differ between relapsed and stable patients. Serum prolactin (PRL) assessed 2 weeks after dose reduction and mean PRL after reduction were significantly lower among relapsers. Serum neuroleptic levels were significantly lower for relapsers in patients on haloperidol. Among relapsers, there were no serum PRL or neuroleptic level differences between stable periods and the relapse episode. Among patients with relatively low neuroleptic bioavailability, relapsers reported lower levels of social activity and had social networks that were less enjoyable, more aversive, and less helpful than those of stable patients. PMID- 2880361 TI - Comparison of two groups of tardive dyskinesia patients. PMID- 2880362 TI - Effect of different neuroleptics in tardive dyskinesia and parkinsonism. A video controlled multicenter study with chlorprothixene, perphenazine, haloperidol and haloperidol + biperiden. Nordic Dyskinesia Study Group. AB - Thirty-three chronic psychiatric patients with tardive dyskinesia (TD) were included in a video-controlled multicenter study of the effect of chlorprothixene, perphenazine, haloperidol and haloperidol + biperiden in TD and parkinsonism. The drugs were given in a cross-over design in randomized order in dosages equipotent to the earlier neuroleptic treatment and administered for periods of 6 months with 6-week placebo periods before and after. A total of 55 treatment periods were completed; only seven patients were able to go through all three treatment phases (= 96 weeks). Perphenazine (20.5 mg/day), haloperidol (5.5 mg/day), and haloperidol (11 mg/day) + biperiden (7 mg/day) induced a moderate suppression of TD and at the same time produced a corresponding aggravation in parkinsonism. Chlorprothixene (142 mg/day) had only a slight TD reducing effect and did not change parkinsonism. Thus the TD suppressing effect was inversely related to the parkinsonian-inducing effect of the neuroleptics. Following withdrawal of the drugs, TD increased in some cases and decreased in others compared to the pretreatment level. No significant correlation was found between the intensity of the withdrawal TD and either drugs or preceding parkinsonism or TD suppression. Only in a subgroup of seven patients who consecutively received all three neuroleptics, perphenazine, but not haloperidol and chlorprothixene, produced a post-treatment aggravation which was correlated to the parkinsonsim and TD suppression during treatment. Independent of the neuroleptic given, the TD intensity increased significantly from the first to the third placebo period. This suggests that drug holidays are inappropriate to prevent TD induction/aggravation. PMID- 2880363 TI - Effects of H1-receptor antagonists on responding punished by histamine injection or electric shock presentation in squirrel monkeys. AB - Squirrel monkeys were trained to press a key under a two-component schedule of food presentation. In the presence of either green or red stimulus lights, the 30th response produced a food pellet (fixed-ratio schedule). During the red stimulus lights (punishment component), the first response of each fixed ratio produced either an IV injection of histamine (100.0 micrograms/kg/inj) or a brief electric shock (3.0 mA). Responding was selectively suppressed in either punishment component. Presession IM administration of chlorpheniramine (0.1 and 0.3 mg/kg), diphenhydramine (1.0 and 3.0 mg/kg), or pyrilamine (0.1 and 0.3 mg/kg) increased rates of responding punished by histamine but not those punished by electric shock. Presession administration of promethazine (0.1-3.0 mg/kg) or tripelennamine (0.1 and 0.3 mg/kg) also increased rates of responding punished by histamine in all subjects and response rates punished by electric shock in one of three subjects. Chlordiazepoxide (3.0-56.0 mg/kg) increased rates of responding punished by either histamine or electric shock. These results suggest that the punishing effects of histamine injection are mediated by H1 receptors and that H1 receptor antagonists increase rates of responding suppressed by punishment only under limited conditions including those in which histamine is the punishing stimulus. PMID- 2880365 TI - [Plasma welding, why?]. PMID- 2880364 TI - Modification of the radioreceptor assay technique for estimation of serum neuroleptic drug levels leads to improved precision and sensitivity. AB - This report describes a series of modifications in the radioreceptor assay procedure for monitoring of serum neuroleptic levels which resulted in a substantial increase in precision and in a higher sensitivity than is the case with existing assays. The use of a dopamine receptor preparation from pig striatum yielded a lower limit of sensitivity for haloperidol of 0.08 ng/ml, when 0.5 ml serum was used in the assay; the intra- and inter-assay coefficients of variation were 3 and 9%, respectively. The relative antipsychotic potency of various neuroleptics correlated with their optimal daily dosage. Anticonvulsants (carbamazepine, phenytoin, barbiturates), anxiolytics (diazepam, bromazepam), as well as other drugs or hormones such as lithium, chloral hydrate, L-tryptophan or L-thyroxine did not interfere with the assay. Simultaneous determination of haloperidol by the radioreceptor assay and radioimmunoassay in serum showed good correlation (r = 0.994). Good correlation was also noted between the average optimal clinical daily dose of the neuroleptics and their affinity to the dopamine receptor of the porcine striatum (r = 0.891). Cross-laboratory assessment indicated good correlation between the estimation of haloperidol by a dopamine receptor preparation from bovine caudata and porcine striata (r = 0.830). The sensitivity of the present assay was improved about 30-fold compared to those previously reported. PMID- 2880366 TI - Infarct size--can it be measured or modified in humans? AB - Despite more than 15 years of intensive experimental and clinical research in the general area of limiting infarct size, no treatment has been shown to be so efficacious and relatively free of side effects that its routine use can be recommended. In addition, there is no ideal means of measuring infarct size as yet. However, considerable progress has been made in understanding mechanisms responsible for irreversible cellular injury and in identifying factors and anatomic alterations responsible for or contributing to the development of transmural (Q wave) and non-transmural (non-Q wave) myocardial infarcts. Interventions are available that are capable of causing rapid coronary thrombolysis, and techniques are becoming available tht have increasing power to size myocardial infarcts and estimate both segmental and ventricular function. Experimental studies have also suggested a potential benefit from a combination of reperfusion therapy with selected pharmacologic intervention in reducing infarct size and preserving ventricular function. It seems likely that this general area will remain an intensive area of clinical research in the immediate future. PMID- 2880367 TI - Brain neurotransmitters and the development and maintenance of experimental hypertension. PMID- 2880368 TI - The effect and usefulness of early intravenous beta blockade in acute myocardial infarction. PMID- 2880369 TI - Mechanisms underlying sensitivity to organophosphorus anticholinesterase compounds. PMID- 2880370 TI - [Use of nifedipine in patients with advanced arteriosclerotic cardiopathy]. PMID- 2880371 TI - Radiology in the Mediterranean countries. PMID- 2880372 TI - [Cervico-thoracic sympathectomy in severe frostbite of the upper extremities]. PMID- 2880373 TI - [Serum lipids and gamma-glutamyltransferase in acute pancreatitis]. PMID- 2880374 TI - [Beta agonist action and function of cyclic AMP in human]. PMID- 2880375 TI - [Effects of several beta 1-selective blockers on the pressor response of the adrenalectomized, pithed rats to electrical stimulations of the spinal nerves]. PMID- 2880376 TI - [The diabetic foot]. PMID- 2880377 TI - [Endomorphins and nociception]. AB - Since the discovery of Met- and Leu-enkephalin (Hughes and Kosterlitz, in 1975) about 20 opioid peptides including beta-endorphin, enkephalins and dynorphins have been identified in the central nervous system. Multiple opiate receptors: mu, delta, kappa, etc, with distinct pharmacological characteristics and regional distributions are present in the CNS, which may correspond to the heterogeneity of opioid peptides. Although both endomorphins and opiate receptors have been found in all areas directly involved in nociception, pharmacological, electrophysiological and most biochemical investigations have not demonstrated so far that endomorphinergic neurones play a role in the control of pain. As emphasized in this review, only the measurement of endomorphin release directly in the CNS has allowed the demonstration that some endomorphinergic neurones, notably those containing Met-enkephalin in the spinal cord, can be activated by noxious stimuli. However, the characteristics of this activation depend on both the nature of the stimulus (chemical, mechanical or thermal) and the body area where it is applied. The functional significance of such "pain"--induced activation of spinal enkephalinergic neurones is still speculative. PMID- 2880378 TI - [11 cases of neuropathy induced by almitrine, of which one had optic neuropathy]. AB - The only etiologic factor retained in 11 patients with sensory or sensory-motor neuropathy was almitrine therapy. In one patient there was in addition an optic neuropathy. The reduction in visual acuity in this patient coincided with the onset of the sensory-motor neuropathy of lower limbs after treatment with 100 mg/day of almitrine over a 2-year period. No other metabolic, inflammatory, toxic, vascular or immunologic cause was found. There was a moderate chronic respiratory insufficiency. Visual recuperation started one month after the arrest of almitrine treatment and was satisfactory 7 months later. The other 10 patients had neuropathy of limbs without visual disorders. Neuromuscular biopsy in one case showed lesions to be of the axonal type. PMID- 2880380 TI - Infrared advanced technology: simplified soldering and glazing procedure. PMID- 2880379 TI - [Idiopathic localized paroxysmal hyperhidrosis. Treatment with clonidine]. AB - Paroxysmal localized hyperhidrosis is a rare sign of a disorder of the autonomic nervous system. It has been reported in association with peripheral nerve, spinal cord and hypothalamic lesions and in some cases the etiology is unidentified. We present 12 cases of idiopathic paroxysmal localized hyperhidrosis and discuss the therapeutic effect and possible mechanism of clonidine which is a specific central nervous system alpha 2--adrenergic receptor agonist. PMID- 2880381 TI - Polyarteritis nodosa in and elderly female. PMID- 2880383 TI - Effect of glutathione and N-acetylcysteine on hepatocellular modifications induced by 2-acetylaminofluorene. AB - The exposure of rats to a dietary regimen containing 2-acetylaminofluorene induces a sequence of hepatocellular alterations leading to the development of preneoplastic nodules. Groups of 2-acetylaminofluorene-treated rats were given glutathione or N-acetylcysteine to evaluate the effects of these different thiols on the sequence of events that originate transformed cells. It is well known that intracellular thiols protect biological macromolecules from scavenging free radicals and electrophilic compounds produced by the metabolism of chemical agents. Male Wistar rats were maintained on a feeding regimen containing 0.05% 2 acetylaminofluorene. The diet of 2 groups of 2-acetylaminofluorene-treated animals was supplemented with either 0.1% glutathione or N-acetylcysteine. The effects in the liver of the exogenously supplied thiols during 2 acetylaminofluorene treatment were assessed evaluating DNA damage, glutathione levels, activity of marker enzymes glucose-6-phosphatase, gamma glutamyltranspeptidase, and glutathione-S-transferase, survival rates, and development of salivary gland tumors. Our results demonstrate that the mortality due to 2-acetylaminofluorene exposure was reduced or completely abolished by thiols and that the development of salivary gland tumors was inhibited. Exogenously supplied thiols significantly reduced DNA damage as assessed by alkaline elution. At the doses employed, glutathione and N-acetylcysteine induce early stimulation of glutathione-S-transferase, had little effect on the loss of glucose-6-phosphatase activity and scanty influence on the net increase in gamma glutamyltranspeptidase activity. PMID- 2880382 TI - Phenotypic characterization of 3H-thymidine incorporating cells in rheumatoid arthritis synovial membrane. AB - Tritiated-thymidine incorporating cells in synovial tissue samples from ten patients with definite or classic rheumatoid arthritis (RA) were studied by combining two techniques. Tritiated-thymidine-labelled cells were seen in autoradiography and simultaneously the subtype of them was determined with immunoperoxidase staining using monoclonal antibodies. Tritiated-thymidine labelled cells comprised 0.8 +/- 0.4% of all the inflammatory cells in RA synovial membrane. Of all 3H-thymidine-labelled cells 34 +/- 17% were positive for OKT8 and 19 +/- 8% for OKT4 monoclonal antibodies. OKM1-positive cells comprised 7 +/- 3% of all 3H-thymidine labelled cells, whereas only a few (3 +/- 4%) of them were positive for pan-B monoclonal antibody. This study emphasizes the importance of activated OKT8 lymphocytes in RA synovial membrane. PMID- 2880384 TI - Further studies on the tumor-initiating activity of the beta-blocker DL-ZAMI 1305. AB - The purpose of this study was to evaluate the initiating activity of the hepatocarcinogen beta-blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butylamino propan-2-ol (DL-ZAMI 1305) by the initiation-promotion protocol of Pereira. Female Wistar rats were given a single dose 150 mg/kg of body weight of DL-ZAMI 1305 by gavage 24 hours before or 24 hours after partial hepatectomy. One week later rats were given phenobarbital (0.05%) in the diet for a period of 7 weeks. DL-ZAMI 1305-treatment resulted in the appearance of gamma-glutamyltranspeptidase foci and of other preneoplastic lesions in all animals. Preneoplastic lesions were also present in a fraction of DL-ZAMI 1305-treated animals not subjected to partial hepatectomy, whether given or not phenobarbital. Results obtained in a separate experiment demonstrated that DL-ZAMI 1305-treatment inhibits cell proliferation and induces DNA damage in the regenerating rat liver. The results of this study clearly demonstrated that the beta-blocker DL-ZAMI 1305 is an initiating carcinogen for the liver of female Wistar rats. PMID- 2880385 TI - [Prevention of recurrent hemorrhage caused by rupture of esophageal varices in cirrhotic patients]. PMID- 2880386 TI - Humoral mediation of the development of the mammalian nervous system. AB - The application of the new ideas advanced by modern neuroscience research, mainly those about the neuronal plasticity and the extrinsic influences able to modify the behaviour of the neuronal populations, to the ontogenetic evolution of the nervous system, have conducted to the elaboration of the concept of the humoral mediation of the brain development. Data sustaining this concept come from at least four areas of investigations, referring to the influences which the endocrine glands (thyroid, gonads, adrenals, hypophysis and pineal), neurotransmitters and the "growth factors" exert on the in vivo and in vitro development of the nervous system. These data are synthetically presented in the present paper, a special attention being paid to the pineal gland and its hormones, due to the personal research of the author in this field. All these researches support some fascinating hypotheses regarding the future of this extremely controversed field of the neuroscience, hypotheses that are presented in the final chapter of the paper. PMID- 2880387 TI - Vector competence experiments with Rocio virus and three mosquito species from the epidemic zone in Brazil. PMID- 2880388 TI - [The activity of Culicidae mosquitoes in plain forests and an epidemiological profile of several environments in the Ribeira Valley, Sao Paulo, Brazil]. PMID- 2880389 TI - Exogenous serotonin and histamine-stimulated gastric acid and pepsin secretion in dogs. AB - The effects of serotonin on histamine-stimulated gastric acid and pepsin secretion were evaluated in conscious dogs with a gastric fistula. Histamine stimulated the acid secretion dose-dependently, whereas pepsin secretion was decreased by the high doses of histamine. The acid secretion was inhibited slightly by serotonin, with a maximum of 42% with a dose of 10 micrograms/kg/min. The pepsin secretion was only decreased non-significantly by serotonin, 10-15 micrograms/kg/min. The acid inhibition was counteracted by beta-adrenergic antagonists (propranolol, atenolol) and methysergide (serotonergic antagonist). The dose-response analysis showed inhibition of a competitive type. In conclusion, serotonin inhibits histamine-stimulated gastric acid secretion via serotonergic receptors and beta-adrenoceptors, whereas pepsin secretion is unaffected. PMID- 2880390 TI - Adrenergic influence on gallbladder function in experimental cholecystitis. AB - In experimental cholecystitis a net secretion of fluid to the gallbladder lumen is seen in animals with morphological signs of acute inflammation. This fluid secretion, which increases the intraluminal pressure in the obstructed gallbladder, is suggested to be influenced by non-cholinergic intramural gallbladder nerves activated by prostaglandins. In the present study in vivo we show that this fluid secretion, measured by a perfusion technique, is markedly inhibited by electrical activation of the splanchnic nerves that contain adrenergic fibres to the gallbladder and by intravenous administration of an alpha 2-adrenergic agonist, demonstrating that this fluid secretion can be modulated by activation of alpha 2-adrenergic receptors. In patients with an obstructed gallbladder outlet, inhibition of this secretion may reduce gallbladder distension and thus relieve biliary pain. The results suggest that pharmacological activation of adrenergic mechanisms could be useful in the treatment of cholecystitis and biliary pain. PMID- 2880392 TI - Thoughts on the treatment of schizophrenia. AB - The author contends that the clinical relationship is the foundation for treating the person with schizophrenia. However, the models and scientific data available to the clinician have been limited by prevailing ideologies. Despite important contributions from interpersonal, pharmacologic, and rehabilitation treatment perspectives, each has curtailed the range of clinical observation and the capacity for integration of treatments. Even recent advances in clinical science methodology have contributed to a short fall in treatment knowledge. The author espouses a broad medical model for defining the range of data and integration of techniques relevant to therapeutics. He views phenomenology as the crucial concept for clinical exploration, and contrasts this approach with the shallowness of purely descriptive approaches on the one hand and the distortion imposed by theoretical presentiments of psychotherapy on the other. Continuity of care and integration of therapies can emerge from phenomenology in the context of the clinical relationship. PMID- 2880391 TI - T-cell chronic lymphocytic leukaemias and T-cell lymphoma-leukaemia: heterogeneity and anomalous cell markers. AB - We studied cell surface markers in 8 men with T-cell chronic lymphocytic leukaemia, using fluorescein-conjugated monoclonal antibodies and a cell analyser/sorter. 1 patient's cells had a T-suppressor/cytolytic phenotype (T4-, T8+) and in 3 patients the phenotype was a T-helper cell (T4+, T8-) as described in retrovirus-associated adult T-cell lymphoma-leukaemia. In 4 patients, the cell phenotype was anomalous, with both helper and suppressor antigenic markers (T4+, T8+). Terminal deoxynucleotidyl transferase was positive in 1 of the 4 cases with dual markers. Clinical features and cytological characteristics, including cell size and the density of T8 antigen on the cell surface, showed no obvious correlation with the immunophenotypes, but study of additional cases is needed to evaluate this further. PMID- 2880393 TI - Applications of experimental psychopathology in psychiatric rehabilitation. AB - Persons with schizophrenia show deficits in basic psychological functions such as attention, perception, and cognition. Remediation of these deficits by direct training may facilitate the effectiveness of neuroleptic medications, social skills training, and family therapy. In the vulnerability-stress model of schizophrenia, persons with schizophrenia may have lower thresholds for disorganization that contribute to vulnerability. Stress increases arousal, which brings many competing responses to the same strength, leading to intrusion of inappropriate responses. Interventions that reduce arousal and lower the strengths of competing responses should reduce psychological deficits. Arousal reducing, attentional, and cognitive interventions are appropriate for the prodromal, acute, and chronic stages of schizophrenic disorders. Laboratory-based assessment and ongoing measurement of basic psychological deficits in schizophrenia are keys to the development and validation of multimodal psychiatric rehabilitation. PMID- 2880394 TI - Social learning for chronic mental inpatients. AB - With chronic institutionalized psychiatric patients, an intensive social learning program resulted in greater increases in adaptive functioning, reductions in bizarre behavior, less prescribed medication, and over 98 percent of patients being successfully discharged into the community. The social-learning program was more cost-effective than custodial hospital care, and nonprofessional staff were able to apply the treatment with a high degree of competence. Especially effective elements of the social-learning program included integrated procedures emphasizing the acquisition of patient skills and the reduction of bizarre, inappropriate behavior; a token economy structure; and consistent pacing and generalization training. More recent research in the area has sought to identify the remediative aspects of social-learning programs, to specify patient variables that are related to improvement in a token economy, and to offer patients more specialized interventions (e.g., social skills training) in conjunction with a standard token economy. With the demonstrated and operationalized efficacy of social-learning procedures, the rehabilitation of chronic psychiatric patients has become more feasible. PMID- 2880395 TI - [The long QT syndrome: importance of phonocardiography and ergometry]. AB - The chronological relationship between the S2 of the phonocardiogram and the T wave of the ECG, and the behaviour of the QT and QTc intervals, have been investigated in two cases of idiopathic long QT syndrome (LQTS) at rest and during effort. At rest and during effort with heart rates (HR) under 120/min, the S2 is always abnormal before the end of the T wave where the QTc interval is generally prolonged, but is sometimes within normal range (less than or equal to 440 msec). In cases where the QTc interval falls within normal range, the use of Bazett's formula to calculate the QTc interval may mislead and cause the existence of LQTS to be overlooked. Study of the chronological relationship (timing) between S2 and T wave is a reliable method of detecting LQTS even with a normal QTc interval. During ergometer exercise, if we observe (as in our two cases) not only a normal acceleration of the HR but a shortening and even a normalization of the QTc interval, therapeutic abstention (betablockers) may be recommended in asymptomatic LQTS. It is concluded that (1) in LQTS at rest and with HR under 120/min, S2 is always abnormal before the end of the T wave, (2) study of the timing S2/T wave is a reliable method of detecting the existence of LQTS even with a normal QTc interval, (3) in asymptomatic LQTS where the QTc interval shortens or falls within normal range during effort with S2 appearing at the end of the T wave, as reported in our first case, therapeutic abstention (betablockers) may be recommended. PMID- 2880396 TI - Studies on glutamine synthetase from Streptomyces hygroscopicus var. jinggangensis. AB - Streptomyces hygroscopicus var. jinggangensis produces validamycin, an important antibiotic used in agriculture. It was found that there was a positive correlation between the specific activity of mycelial glutamine synthetase (GS) and validamycin biosynthesis in our laboratory. So, in this paper, the purification, characteristics and regulatory properties of GS are reported. The native enzyme had a molecular weight of approximately 530,000 and was composed of 12 identical subunits, each 43,000. Electronic microscopic examination of preparations negatively stained disclosed that the subunits were arranged in two hexagonal rings that lay one on top of the other in a face-to-face fashion. Mg2+ or Mn2+ was absolutely needed as cofactor for GS activity. The enzyme activity was regulated by feedback inhibition and cumulative feedback inhibition. In addition, it was also regulated through a covalent modification, adenylylation and deadenylylation, suggesting that the covalent modification of GS exists not only in Gram-negative bacteria but also in some Gram-positive bacteria. PMID- 2880397 TI - Tetrahydroprotoberberine--a new chemical type of antagonist of dopamine receptors. AB - In rats lesioned by unilateral micro-injection of 6-OHDA into substantia nigra, the apomorphine-induced contralateral rotation and the amphetamine-induced ipsilateral rotation were antagonized by THB, l-THP and haloperidol. Scopolamine reversed the antagonistic effect of THB against amphetamine. Thus, THB and l-THP exhibited the DA-receptor antagonistic property which was similar to that of haloperidol. l-SPD (10 mg/kg), however, only antagonized the amphetamine challenged rotational response, while it could not antagonize, but potentiate, the apomorphine-challenged rotational response. So, l-SPD might be a partial agonistic antagonist of DA-receptors, and its effect was more potent than that of THB and l-THP. l-SPD would be ascertained further in clinic trial. From these results and others, the authors suggest that THPB is a new chemical type of antagonist of brain DA-receptors. PMID- 2880398 TI - A sequence in M13 phage detects hypervariable minisatellites in human and animal DNA. AB - The term "DNA fingerprint" has been used to describe the extensive restriction fragment length polymorphism associated with hypervariable minisatellites present in the human genome. Until now, it was necessary to hybridize Southern blots to specific probes cloned from human genomic DNA in order to obtain individual specific restriction patterns. The present study describes the surprising finding that the insert-free, wild-type M13 bacteriophage detects hypervariable minisatellites in human and in animal DNA, provided no competitor DNA is used during hybridization. The effective sequence in M13 was traced to two clusters of 15-base pair repeats within the protein III gene of the bacteriophage. This unexpected use of M13 renders the DNA fingerprinting technology more readily available to molecular biology laboratories. PMID- 2880399 TI - The genetic defect causing familial Alzheimer's disease maps on chromosome 21. AB - Alzheimer's disease is a leading cause of morbidity and mortality among the elderly. Several families have been described in which Alzheimer's disease is caused by an autosomal dominant gene defect. The chromosomal location of this defective gene has been discovered by using genetic linkage to DNA markers on chromosome 21. The localization on chromosome 21 provides an explanation for the occurrence of Alzheimer's disease-like pathology in Down syndrome. Isolation and characterization of the gene at this locus may yield new insights into the nature of the defect causing familial Alzheimer's disease and possibly, into the etiology of all forms of Alzheimer's disease. PMID- 2880400 TI - Linkage disequilibrium between a marker on the LDL receptor and high cholesterol levels. PMID- 2880401 TI - Non-insulin-dependent diabetes mellitus and the 5' hypervariable region of the insulin gene in two South African Indian families. AB - The hypervariable region 5' to the human insulin gene has been characterised in two South African Indian families, each having two generations of individuals affected with non-insulin-dependent diabetes mellitus (NIDDM). Southern blot analysis, with the restriction endonuclease Pvu II and plasmid phins 310 as a probe, was used. In family 1, class 1 alleles (0.87, 0.79, 0.72 and 0.68 kilobase (kb)) were found at this locus but no linkage with NIDDM was shown. In family 2 a class 3 (2.51 kb) and two class 1 alleles (0.89, 0.76) were found. The 0.89 kb allele appears to be segregating with NIDDM in this family. PMID- 2880402 TI - [Prospectives on the use of urinary enzymes in oncology and radiotherapy]. PMID- 2880404 TI - Informed consent for the use of antipsychotic medications: one standard for all? PMID- 2880405 TI - [Residual effects on the equilibrium of 3 hypnotics (loprazolam, flunitrazepam, triazolam) assessed by spectrum analysis of postural oscillations]. PMID- 2880403 TI - Molecular aspects of murine systemic lupus erythematosus. PMID- 2880406 TI - [Desensitization of beta-adrenergic receptors at the bronchopulmonary level]. PMID- 2880407 TI - Tyrosine hydroxylase activity in blood platelets, plasma and leucocytes. PMID- 2880408 TI - [Essential linolenic fatty acid deficiency. Patients on long-term gastric tube feeding]. PMID- 2880409 TI - [The Tavistock conferences on group relationships. A different training for leadership and organization]. PMID- 2880410 TI - An overview of the restriction fragment length polymorphism of the HLA-D region: its application to individual D-, DR- typing by computerized analyses. AB - HLA-D/DR alleles as defined by cellular and serological typing can also be identified by biochemical methods. The Southern blot technique provides an additional typing facility which can be applied to DNA obtained from any source of nucleated cells. The polymorphism revealed by Southern blot analyses, the so called restriction fragment length polymorphism (RFLP), depends upon the restriction enzyme and cDNA probes used. To identify HLA-DR specificities a protocol was developed based on the use of the results of southern blot analyses with several restriction enzymes and cDNA probes within a panel of HLA-D/DR homozygous cells representing the DR1 to DRw8 alleles. First, hybridizations with the 3' untranslated sequence of the DR beta cDNA probe, after digestion of the DNA with PvuII (PvuII-DR beta 3') allows the selective identification of DR1, DR2 and DRw8; DR3, DR5 and DRw6 are found as one group as well as DR4 and DR7 as another. Second, TaqI-DQ alpha hybridization allows the splitting of DRw6-Dw18, DRw6-Dw19 and DRw6-Dw9 from the DR3, DR5 and DRw6 group. The other alleles DR3, DR4, DR5, DRw6-Dw16 and DR7 are revealed by dehybridization and rehybridization of the blot with a DR beta cDNA probe. This protocol was used to test whether in a panel of 30 randomly chosen individuals the HLA-DR typing could be performed. The results were highly concordant to the serotyping. Furthermore by adding the Pst-DR beta and TaqI-DQ alpha RFLPs, most of the MLC defined Dw specificities could also be identified. An overview of the specific fragments described here has been summarized in matrices which can be used as references for DNA-typing in computerized analyses. PMID- 2880411 TI - Regional differences of responses to adrenoceptor agonists in isolated and perfused canine coronary arteries. AB - Regional differences of the responses to adrenoceptor agonists were investigated in isolated canine coronary arteries by use of a cannula inserting method. Acetylcholine induced a dose-dependent vasodilation. Norepinephrine and epinephrine produced a vasoconstriction followed by a strong vasodilation in large coronary arteries and only a weak vasodilation in small coronary arteries. Phenylephrine (a selective alpha-1 agonist) induced a strong vasoconstriction in both arteries. The threshold dose and ED50 value for phenylephrine in small coronary arteries were much larger than those in large coronary arteries, although the vasoconstrictions by KCl and prostaglandin F2 alpha were not different between in large and small coronary arteries. Clonidine and xylazine (selective alpha-2 agonists) produced a slight vasoconstriction but not dose dependently and a vasodilation with extremely large doses. ED50 value of vasodilation for salbutamol (a selective beta-2 agonist) was approximately 80 times greater than that for isoproterenol (a non-selective beta-agonist) in large coronary arteries, but was approximately 20 times in small coronary arteries. The maximal dilator response to salbutamol was about the same as that to isoproterenol in small coronary arteries, whereas it was much smaller than that to isoproterenol in large coronary arteries. These results suggest that adrenoceptors are heterogeneous according to the distance from the coronary orifice in canine epicardial coronary arteries. PMID- 2880412 TI - Plasma somatostatin response in normal and gastrectomized subjects. AB - The present work was undertaken to investigate a possible contribution of the stomach to plasma concentrations of somatostatin-like immunoreactivity (SLI) in humans. For this purpose, plasma SLI responses were determined in previously gastrectomized subjects during lipid-heparin induced elevation of plasma free fatty acids (FFA), which gave a consistent rise of plasma SLI in normal controls. Fasting plasma SLI levels in both the subjects with antral and total gastrectomy did not differ from the values in normal controls. Acute elevation of plasma FFA resulted in about 5-fold increase of plasma SLI above basal level in the controls. In contrast, in both the gastrectomy groups there was no significant rise in plasma SLI, despite a comparable elevation of plasma FFA levels. In conclusion, these findings demonstrate that the stomach, probably the antral region of the stomach, accounts for the most part of increase of plasma SLI when hyperfatty-acidemia is induced and suggest that following the stimulation by nutrients the stomach makes a greater contribution to plasma SLI levels than does the pancreas or extragastric intestinal tract in humans. PMID- 2880413 TI - Preparation of a toxic derivative of sea anemone toxin II from Anemonia sulcata which has peroxidase activity. AB - Sea anemone toxin II (ATX II) is a useful tool for investigation of sodium channels in excitable membranes. Coupling of ATX II with microperoxidase, a heme octapeptide, is described. The isolated cross-linked product possesses both toxic and peroxidase activity. The lowest concentration of the modified toxin that affects the action potential and the membrane currents in single cardiac myocytes is 16 nM. The enzymatically active ATX II derivative may be useful for biochemical applications and as a non-radioactive tracer for electron microscopy studies of excitable tissue. PMID- 2880415 TI - [Seasonal variations of dental injuries]. PMID- 2880414 TI - Beta-adrenergic blockade after stroke. A preliminary closed cohort study. AB - To collect background data for a prospective clinical trial of beta-blocking agents in the prevention of deaths after stroke, the long-term prognosis in 60 patients discharged from a stroke unit on beta-blocker therapy was compared with the outcome in 60 matched patients with stroke but without beta-blockers. Matching included sex, age, type of stroke, and presence or absence of hypertension and cardiac failure. Thirteen patients (22%) in the beta-blocker group died during a median followup of 41 months. Of the 60 patients not on beta blockade at discharge, 21 (35%) died during a median followup of 36 months. By life-table technique and log-rank test, the relative risk for death was 0.60:1.00 (p = 0.14). During followup, 12 recurrent strokes were observed in patients on beta-blockers and 19 in patients without beta-blockers (relative risk 0.57:1.00; p = 0.12). It appeared that the reduction in mortality could only marginally be ascribed to fewer deaths from myocardial infarction; other causes of death were also less frequent in beta-blocker-treated patients. The results emphasize that supplementary information on the effect of beta-blocking agents on mortality after stroke is needed before a larger trial of beta-blocker therapy in patients with manifest cerebrovascular disease can be initiated. PMID- 2880416 TI - In vitro colonization of thymic primordia by adult bone marrow cells: light scatter profile and separation by flow cytometry. AB - Adult mouse bone marrow showed a reproducible scatter profile on low angle vs. right angle scatter by flow cytometry and it was possible to sort cells from different regions of the profile. The colonization of the third pharyngeal pouch in vitro was used as a test of thymocyte precursors. Alleles of the Thy-1 surface antigen, as well as the nuclear chromatin pattern of the ichthyosis mutant, were used to monitor chimerism. Thymus-colonizing cells were found in one region of the scatter profile, and these cells were negative for Thy-1 and Ia markers. PMID- 2880417 TI - Presence of cells with argyrophil granules in normal, hyperplastic, and neoplastic endometrium. AB - Cells with argyrophil granules were searched for in 131 consecutive specimens obtained from endometrial curettage. Particular care was taken with the fixation methods to avoid a false positivity to the silver impregnation according to Grimelius. We did not consider the grossly argyrophilic positivity on the cellular apex or of the whole cytoplasm, which was partially reduced by diastase digestion and probably due to the presence of glycogen and secretory mucoproteins. Cells with thin argyrophilic granules similar to those observed in endocrine APUD cells were present among glandular cells and/or among stromal cells in 15 of 131 examined specimens. They concerned 5 cases of proliferative endometrium, 3 of secretive endometrium, 5 of hyperplasia, and 2 of carcinoma. In 8 of the 15 cases with argyrophilic cells, immunohistochemical studies with the PAP method showed cells with the presence of FSH, S-100 protein, somatostatin, vasoactive intestinal peptide (VIP), gastrin, and neuron-specific enolase (NSE). The significance and origin of these cells in normal and neoplastic endometrium are discussed. PMID- 2880418 TI - [Treatment of uncontrollable consumption of opioids in chronic pancreatitis. A model used in 17 consecutive patients]. PMID- 2880419 TI - Effects of high pressure on the release of excitatory amino acids by brain synaptosomes. AB - Excitatory amino acid antagonists have been shown to protect against the hyperexcitability associated with exposure to high pressure. This suggests that these excitatory neurotransmitter substances may play a role in the development of the symptoms of high pressure nervous syndrome (HPNS). Using a superfusion technique, we investigated the effect of exposure to 67.7 ATA of pressure on the release of aspartate and glutamic acid by isolated presynaptic nerve terminals from the guinea pig cerebral cortex. Pressure exposure was found to significantly increase the depolarization-induced release of aspartate by these synaptosomes. On the other hand, compression to 67.7 ATA had no effect on glutamic acid release. These findings suggest that increased aspartate release may be a contributing factor in the etiology of HPNS. PMID- 2880420 TI - [Anesthesiologic aspects of extracorporeal shockwave lithotripsy (ESWL)]. AB - Anesthesiological considerations are discussed on the basis of the limited literature available and our own experience with more than 2000 ESWL treatments. Guidelines concerning anesthesia technique and ESWL treatment of renal and ureteral stones are outlined and compared to our own results and those in the literature. The following techniques are discussed: intubation anesthesia with halogenated carbohydrogens (Fluothane, Ethrane), intubation anesthesia with Fluothane/Ethrane plus opiates, neuroleptic anesthesia, catheter peridural anesthesia (lumbar/thoracic), opiate analgesia and high frequency jet ventilation. PMID- 2880421 TI - Preliminary characterization of Escherichia coli isolated from pigs with diarrhoea in Venezuela. AB - The aetiology of neonatal porcine diarrhoea was studied in 15 different herds located in the north-western region of Venezuela. Of 56 strains of Escherichia coli analyzed, 16 (28.6%) were shown to produce heat-stable (STa) enterotoxin, as detected by infant mouse assay. Only four of these STa+ isolates also possessed the K88 pilus antigen, two were 987P+ and none possessed the K99 antigen, leaving 10 STa+ samples in which no pilus antigen was identified. Among the 40 STa negative samples were six K88+ specimens, one K99+, four 987P+, one which reacted as K88+ + K99+ and one K88+ + 987P+. Considering as pathogenic any strain showing at least one of the characters studied, pathogenic E. coli were detected with an overall frequency of 42.9%, being more prevalent during the second week of life. An electrophoretic analysis of the plasmid content of the field isolates of E. coli, revealed the presence of numerous species of extrachromosomal DNA, although no direction association could be made between a particular plasmid and any of the pathogenic characteristics identified. Results of Southern blot analysis indicate that the STa enterotoxin was preferentially encoded within an endemic plasmid of 4.9 Md. Other plasmids present in the E. coli isolates could be related to antibiotic resistance. With the exception of one strain, all E. coli isolates were resistant to more than one of the nine drugs tested; multiresistant E. coli were frequently isolated, including four strains which were resistant to seven antibiotics. PMID- 2880422 TI - Features of enterotoxigenic Escherichia coli strains of porcine origin that express K88 and 987P fimbrial antigens. AB - Escherichia coli strains of porcine origin express K88 and 987P pilus-antigens in vitro. This study reports their enterotoxin producing ability, serological features and plasmid content. The bipiliated strains were enterotoxigenic and all contained a large plasmid of uniform size. PMID- 2880423 TI - [With gratitude in my heart]. PMID- 2880424 TI - Effect of human immunoglobulin preparations on experimental Bordetella pertussis infection in mice. AB - The effects of four kinds of human immunoglobulin preparations for intravenous use [pH-4-treated (IG-100), polyethyleneglycol-treated (PEG-G), sulfonated (S-G) and pepsin-treated (Pep-G)] on intracerebral (i.c.) Bordetella pertussis infection in mice, and on B. pertussis vaccine-induced leukocytosis-promoting factor (LPF) and histamine-sensitizing factor (HSF) were compared with those of human immunoglobulin preparation for intramuscular use (GGN). A prophylactic potential against i.c. B. pertussis challenge was demonstrated in IG-100, PEG-G and GGN. A prophylactic potential was also demonstrated in S-G and Pep-G, although to a lesser extent. Neutralizing activity for LPF was in the following order: GGN = IG-100 = PEG-G greater than S-G = Pep-G; for HSF it was as follows: IG-100 greater than PEG-G greater than GGN = S-G greater than Pep-G. There were no significant differences in antibody titers of the various preparations against B. pertussis antigens. These results suggest that the Fc part of the immunoglobulin molecule is important for protecting against i.c. B. pertussis infection and for neutralizing B. pertussis toxins. PMID- 2880425 TI - [Drug therapy of chronic inflammatory intestinal diseases--current status of 5 aminosalicylic acid]. AB - Assessment of the nature, location and extent of the disease, disease activity and the intestinal and extraintestinal complications and manifestations is an essential prerequisite in the treatment of inflammatory bowel disease. Corticosteroids, sulfasalazine (SASP) and rectal administration of 5 aminosalicylic acid (5-ASA) are effective in the treatment of ulcerative colitis. Oral 5-ASA in the form of a slow-release preparation is probably also effective. Rectal SASP or 5-ASA in addition to corticosteroids is indicated in distal colitis. In severe pancolitis oral or intravenous corticosteroids are required, whilst in less severe forms SASP or 5-ASA can be used. However, the safety of 5 ASA over longer treatment periods has yet to be verified. Surgery is indicated in colitis refractory to maximal treatment over several months. Apart from parenteral or enteral nutrition, treatment with prednisolone is effective in acute exacerbations of Crohn's disease. SASP is possibly effective in colonic disease. The role of 5-ASA has yet to be defined. A prednisolone-induced remission can be maintained by means of low doses of prednisolone. SASP is probably not effective, whilst with 5-ASA conclusive data are missing. Metronidazole and azathioprin are considered to be reserve drugs and can be used in the treatment of fistulae or in order to cut down the dosage of prednisolone during remission. Substitution with vitamins and trace elements is necessary in a large number of patients with Crohn's disease. PMID- 2880427 TI - [Experimental sleep induction: physical and cognitive-emotional variations of psychological fatigue during a short daytime nap]. PMID- 2880426 TI - [New aspects of senile and presenile dementia]. AB - Problems of research in dementia are presented. It is a matter both of structural disturbances in the texture of conditions which impair the texture of conditions of possible functions, as well as of actual functional disturbances of the brain. The numerous etiological and diagnostic aspects resulting from this show distinctly that the dementia does not exist. In the numerous dementias which appear as diseases of higher age, the distinction between true old age diseases (Alzheimer, Pick, progressive glial dystrophy) and the cerebrovascular dementias (multi-infarct-dementia, Binswanger's disease) is of importance. The classification of dementias may be carried out both by descriptive neuropathological criteria and by functional neuropathological criteria. This is demonstrated by way of examples. PMID- 2880428 TI - [Tularemia--report of 2 cases without detectable contact with animals]. PMID- 2880429 TI - [Hiob syndrome. A case report of multiple endocrine neoplasia]. AB - It is reported on a now 48-year-old male with a multiple endocrine neoplasia (MEN I). The most impressive symptomatology issued from a relapsing organic hyperinsulinism the cause of which were multiple islet cell tumours. Up to now the hyperparathyroidism was not mastered by the removal of two adenomas of the parathyroid gland. As third fact in this clinical picture, called also Hiob syndrome, the hypophyseal manifestation developed in form of a space occupation with a hypersomatotropism, the course and final clarification of which are still open. PMID- 2880430 TI - [Functional characterization of luminal enterocyte membranes of the small intestine mucosa using isolated brush border membranes]. AB - Atrophy of the small intestinal mucosa is functionally characterized by a reduction in non-electrolyte transport in vivo. In order to elucidate the cellular defect being responsible for this malabsorption, we have studied the Na+ dependent D-glucose accumulation as well as the activities of aminopeptidase M and maltase in brush border membrane vesicles prepared from jejunal self-emptying blind loops and corresponding intestinal segments of sham-operated control rats. Membrane vesicles from atrophic mucosa did not show any differences in D-glucose uptake or in enzyme activities when compared with those derived from normal intestine. Thus it is unlikely that the impaired non-electrolyte absorption in the atrophic mucosa in vivo is due to a defect in cellular transport processes. It is more probable that the functional impairment is the result of the diminished absorptive surface in this pathophysiological condition. PMID- 2880431 TI - [Treatment of urticaria with the new H1 antihistaminic astemizole--with special reference to the time of onset of effect and maximum effect]. AB - 20 patients, 12 suffering from chronic urticaria, 2 from acute urticaria, 1 from pressure urticaria, 2 from cold urticaria and 3 from urticaria factitia were treated in an open pilot study with the new H1-antihistamine Astemizole. The dosage was in all cases 1 X 10 mg per day. The onset of action as well as the efficacy maximum were registered. Astemizole proved in this study to be a very effective antihistamine being able to achieve good results even in hard to cure cases like cold urticaria. On the 1. day 35% of the patients had noticed an onset of action. 75% of the patients had an onset of action within the first 2 days. The efficacy maximum was achieved within the first 2 days in 60% of the patients. PMID- 2880432 TI - [Clinical significance of computerized tomography of the posterior area of the foot]. AB - Computertomographic examinations of the hindfoot in the frontal and horizontal view will show us morphological findings, which we could not see with conventional X-ray-technique. Out of these findings we are able to control our operative reconstruction as well as late changes in bone healing. The horizontal view will show us the osseous structures of the talus and calcaneus as well as of the navicular and cuboid bone, as it is necessary for preoperative evaluation of the hindfoot. PMID- 2880434 TI - [Early stages and course of Wegener's granulomatosis]. PMID- 2880433 TI - [Organization and suprabulbar control of the baroreceptor reflex arch]. PMID- 2880435 TI - [Comparative study of the pharmacological properties of sultopride sulpiride and other antipsychotic drugs: influence of sultopride, sulpiride and other antipsychotic drugs on spontaneous locomotor activity and changes in locomotor activity induced by apomorphine and clonidine in mice]. AB - To elucidate pharmacological properties of sultopride and sulpiride, their effects on spontaneous locomotor activity, apomorphine-induced hyper- and hypoactivity, and clonidine-induced hypoactivity in mice were examined by use of a photocell activity meter in comparison with the effects of other antipsychotic drugs. Sultopride did not affect spontaneous locomotor activity, whereas it potentiated apomorphine-induced hyperactivity at low doses and inhibited it at high doses. Sultopride also dose-dependently antagonized apomorphine-induced hypoactivity at limited doses. By contrast, sulpiride, in a wide range of doses, exhibited enhancement of apomorphine-induced hyperactivity and antagonization of apomorphine-induced hypoactivity. Furthermore, the activities of sulpiride were more potent than those of sultopride. Haloperidol and chlorpromazine inhibited spontaneous locomotor activity and apomorphine-induced hyperactivity and slightly antagonized apomorphine-induced hypoactivity. Pimozide increased spontaneous locomotor activity but inhibited it at high doses, while also potentiating apomorphine-induced hyperactivity at small doses and inhibiting it at large doses. Pimozide did not markedly affect apomorphine-induced hypoactivity. None of the drugs studied except for imipramine and yohimbine affected clonidine-induced hypoactivity. These results indicate that sultopride has somewhat different pharmacological properties from those of sulpiride and other antipsychotic drugs. These results also suggest that sultopride would have good therapeutic efficacy in schizophrenic disorders. PMID- 2880437 TI - [Covering soft tissue defects of the foot with a free microvascular flap]. PMID- 2880438 TI - A case of multiple endocrine adenomatosis type 1. AB - A case of pituitary adenoma associated with pancreatic islet cell tumor is presented. A 29-year-old man with symptoms of confusion and abnormal behaviour was admitted to the neurosurgical department. He was diagnosed as suffering from multiple endocrine adenomatosis (MEA) type 1. Screening of his family members revealed that his mother had high levels of gastrin, glucagon and parathormone and his father had a high level of gastrin. The pituitary adenoma and pancreatic tumor were removed satisfactorily. Family members as well as the patient should be checked periodically. PMID- 2880436 TI - [Renal dipeptidylpeptidase IV excretion in drug-induced kidney changes]. AB - The course of the excretion of dipeptidyl-peptidase IV (DP IV)-alanine aminopeptidase, beta-glucuronidase and total protein with the urine was investigated during the treatment of 11 patients with pyelonephritis with gentamicin, after application of a renal radiographic contrast medium in 7 patients with arterial hypertension and after regional perfusion of an extremity in 10 patients with malignant melanoma. In the reference group in male test persons with 147.0 nmol/s X l a higher DP IV activity in the urine was recognized than in the female test persons (100.0 nmol/s X l). After application of the drugs a rhythmically intermitting increased excretion of all enzymes mentioned develops. The study confirms the usuability of the DP IV-activity for enzymological investigations of the urine. PMID- 2880439 TI - [Treatment of Tourette syndrome]. AB - A total of 150 patients with Tourette's syndrome were treated by different neurotropic drugs. A conclusion has been made that pimozide (orap) is the drug of choice in the treatment of this syndrome. In cases of drug resistance the author recommends the use of cholinolytic comatose therapy. Long-acting neuroleptics have also been effective. PMID- 2880440 TI - [Clinical and experimental studies of the role of neuromediator systems in the pathogenesis of neurosis and neurosis-like states]. AB - Clinical studies revealed a significant increase in the peripheral blood levels of noradrenaline in patients with different forms of neurosis and neurosis-like states as compared to control subjects as well as heterogeneous or unidirectional but differently pronounced changes in blood levels of acetylcholine and adrenaline. Comparison of the clinical findings with the results of dynamic assays for peripheral levels of acetylcholine and catecholamine in dogs exposed to special psychogenic and physiogenic impacts has helped to form an understanding about some common mechanisms of the formation of neuroses and neurosis-like states. The authors emphasize the consistency of neuromediator shifts in the blood of patients and the possibility of using this parameter for the differential diagnosis of various forms of neurotic disturbances at the initial stage of the disease. PMID- 2880441 TI - [Adjustment of the skin and soft tissues in the area of the foot, calf and thigh amputation stump]. PMID- 2880442 TI - Comparison of two tests to recognize or exclude 5 alpha-reductase deficiency in prepubertal children. AB - Plasma testosterone (T, nmol/l) and dihydrotestosterone (DTH, nmol/l) were measured in 54 children and young adults with male pseudohermaphroditism (46XY, no defect of steroid biosynthesis) 4 h after im injection of testosterone propionate (25 mg/m2, group 1, N = 18), or before and 2, 4 and 6 days after hCG (5000 IU/m2 im, group 2, N = 36). The response to hCG was also studied in 5 control children (unilateral cryptorchidism, group 3) and that to testosterone propionate in a gonadectomized child with confirmed 5 alpha-reductase deficiency. Mean T (133.1 +/- 14.0, SEM) and DHT (17.1 +/- 2.6) in group 1 were higher than in group 2 (17.3 +/- 2.1 and 2.9 +/- 0.4), but there was not significant difference in the T/DHT ratios (group 1: 10.7 +/- 2.0; group 2: 7.2 +/- 0.6). Following testosterone-propionate, there was a negative correlation of T with age (r = -0.723). After hCG, T and DHT were lower in the prepubertal children than in those under 2 or over 10 years, and the T/DHT-ratio rose with age. Two children from group 1 had a T/DHT-ratio above 18, but urinary aetiocholanolone/androsterone (Ae/A) ratios were normal. In the child with 5 alpha-reductase deficiency, the T/DHT ratio was 60, and the urinary Ae/A ratio high. We concluded that the two tests are suitable for confirming or excluding 5 alpha-reductase deficiency in prepubertal children, in whom basal DHT is too low for evaluation, but that physiological age-related changes in 5 alpha-reductase activity have to be taken into consideration. PMID- 2880443 TI - Parathyroid hormone release in vitro in hyperparathyroidism associated with multiple endocrine neoplasia type 1. AB - Hyperparathyroidism (HPT) in the syndrome of multiple endocrine neoplasia type 1 (MEN-1) exhibits a different picture regarding its propensity for recurrence compared with sporadic primary HPT. In order to shed further light on the MEN-1 syndrome an investigation in vitro was made of parathyroid hormone (PTH) release of dispersed parathyroid cell from 11 patients with parathyroid hyperplasia associated with MEN-1, 10 patients with single parathyroid adenomas, and 10 preparations of normal bovine parathyroid glands. The two patient groups had the same average serum calcium value prior to surgery. Immunoreactive concentrations of PTH were measured after 2-h incubations at extracellular calcium concentrations of 0.5-3.0 mmol/l. Compared with the normal bovine parathyroid cells, the cells of the MEN-1 patients had a reduced calcium sensitivity of the PTH release and secreted smaller amounts of hormone at both low and high extracellular calcium concentrations. A similar abnormality of the PTH release was found for the cells of the hyperplastic and adenomatous parathyroid glands. Although individual parathyroid glands were investigated in only three MEN-1 patients, the results suggested the secretory regulation to be less defective in the small glands of each patient. It is concluded that in patient groups matched for serum calcium, the parathyroid tissue of MEN-1 patients has an abnormality of the PTH release similar to that of parathyroid adenomas. PMID- 2880445 TI - Transmission of HTLV-1 by blood transfusion in an ATL-non-endemic area. PMID- 2880444 TI - Dynorphin-(1-13) is a potent in vivo suppressor of vasopressin levels in the rat. AB - Intracerebroventricular administration of dynorphin-(1-13) inhibits dose dependently plasma vasopressin level in normal as well as in water-deprived rats, whereas systemic (subcutaneous) administration of this opioid peptide is ineffective in this respect. Simultaneous subcutaneous, but not intracerebroventricular, administration of naloxone prevents the suppressive effect of dynorphin-(1-13) on plasma vasopressin levels. PMID- 2880446 TI - Benzodiazepines and neuromuscular blocking drugs in patients. AB - The interaction between four benzodiazepines (diazepam, lorazepam, lormetazepam and midazolam) and two nondepolarizing neuromuscular blocking drugs (vecuronium and atracurium) was investigated in 113 patients during general anaesthesia. Neuromuscular function was monitored by recording the mechanical twitch tension of the adductor pollicis muscle of the thumb in response to ulnar nerve stimulation with single supramaximal stimuli of 0.2 ms at 0.1 Hz. In the first group of patients a benzodiazepine (diazepam 20 mg, lorazepam 5 mg, lormetazepam 2 mg or midazolam 15 mg), was injected i.v. 15 min before a single bolus of vecuronium 45 micrograms kg-1. In the second group of patients suxamethonium 1 mg kg-1 was given for endotracheal intubation, and 30 min later the patients received atracurium 200 micrograms kg-1. Fifteen min before injection of atracurium one of the same benzodiazepines as in the first group was injected i.v. Comparisons were made with control patients receiving thiopentone. Neither benzodiazepine caused significant potentiation of neuromuscular blocking agents in comparison with control. With midazolam, however, the duration to 25% and to 75% recovery of the twitch height after vecuronium was significantly longer than with diazepam. The time to 25% recovery of the twitch height after atracurium was significantly longer in patients receiving midazolam than in those receiving diazepam. The recovery index was not influenced by the four benzodiazepines. PMID- 2880447 TI - Oral temazepam as a premedicant in elderly general surgical patients. AB - In elderly, general surgical patients, oral temazepam 20 mg given in a soft gelatin capsule proved to be a useful light premedicant when given before spinal anaesthesia. In comparison with placebo, it caused preoperative subjective sedation, prevented an increase in heart rate and decreased serum cortisol, but not serum antidiuretic hormone levels. However, simple devices (linear analogue scale, Maddox wing test, critical flicker fusion apparatus) appeared to be quite ineffective in differentiating the clinical effects of temazepam from those of placebo. Temazepam given in a soft gelatin capsule to patients in the supine position had a reasonably fast gastrointestinal absorption, but its blood-lumbar cerebrospinal fluid penetration rate appeared to be quite slow. PMID- 2880448 TI - Regulation of glutamate dehydrogenase activity and ammonia production in a nitrogen fixing cyanobacterium. AB - A glutamate auxotroph was obtained in Nostoc muscorum by induced mutagenesis with nitrosoguanidine. The metabolic pathway leading to glutamate synthesis was traced by selecting several enzymes. The strain was found to be lacking glutamate dehydrogenase. Other enzymes, however, were normal in their activity including isocitric dehydrogenase, glutamine synthetase and glutamate synthase. Nitrogen metabolism of the auxotroph and wild type was compared. The strain released exceedingly high amounts of ammonium in the medium. PMID- 2880449 TI - [The interactions between dihydroetorphine, L-tetrahydropalmatine, B-7601 and diazepam]. PMID- 2880451 TI - Effect of prolonged treatment with neuroleptics on dopamine D-1 and D-2 receptor density in corpus striatum of mice. AB - The effects of long-term treatment with neuroleptics on D-1 and D-2 receptor parameters in corpus striatum were studied in mice. Mice were treated daily for 12 days with the selective D-1 antagonist, the benzazepine SCH 23390, the mixed D 1/D-2 antagonist zuclopenthixol or the selective D-2 antagonist haloperidol. Three days after withdrawal Bmax and KD for 3H-SCH 23390 binding to D-1 receptors and 3H-spiperone binding to D-2 receptors were determined. The study showed that the density of D-2 receptors increased after haloperidol whereas no changes were seen after SCH 23390 or zuclopenthixol. No changes in D-1 receptor density were seen after either treatment. The results are in full agreement with published behavioural results where haloperidol induces tolerance whereas SCH 23390 or zuclopenthixol do not. Some changes in KD values were seen. The cause and meaning of these changes await further investigation. PMID- 2880450 TI - Actions of 1,1,1-trichloroethane on the cAMP metabolism in mouse brain. AB - Inhalation or intraperitoneal administration of 1,1,1-trichloroethane (TCE) increased the cAMP content in the brain stem in a dose-related and time-dependent fashion. TCE had no effect on the cAMP level in the cerebellum and hippocampus, but slightly reduced that in the cerebral cortex. Following intraperitoneal administration of TCE the activity of norepinephrine- and F- -activated adenylate cyclase (AC) in a brain stem homogenate was enhanced, while the serotonin stimulated AC activity was decreased. Neither the basal AC activity nor the guanine nucleotide- and forskolin-activated enzyme was affected by TCE. TCE had no effect on the soluble cAMP-dependent phosphodiesterase activity. It is suggested that the increased cAMP content in the brain stem induced by TCE may be mediated via adrenoreceptor interaction with the guanine nucleotide-binding regulatory component, resulting in activation of the catalytic unit of the adenylate cyclase and thereby an increase in the cAMP level. PMID- 2880452 TI - Circadian variations in the acute toxicity of adrenoceptor blocking agents in spontaneously hypertensive rats. PMID- 2880453 TI - In vivo analysis of alpha-adrenoceptors in pial veins of cats. PMID- 2880454 TI - Beta-receptor-mediated vasodilation in cerebral arteries of the pig. PMID- 2880455 TI - Vagal and splanchnic neural influences on gastric and duodenal bicarbonate secretions. An experimental study in the cat. AB - HCO3(-)-secretion by the gastroduodenal epithelium is probably an important factor in the mucosal defence against luminal H+. The aim of this study was to establish the existence of autonomic nervous influence on gastroduodenal HCO3(-) secretion and to present some pharmacological characteristics. Experiments were performed on chloralosed cats with ligated adrenals. The vagal nerves were cut at the cervical level and arranged for electrical stimulation. The sympathetic splanchnic nerves were either cut or left intact. A gastric perfusion technique was developed which allowed simultaneous measurements of gastric motility and H+ and HCO3(-)-secretions, the latter being estimated from measurements of pH and pCO2 in the perfusate (isotonic NaCl). This technique was evaluated both ex vivo and in vivo. A distal segment of the duodenum was cannulated in situ and the lumen was perfused with recirculating isotonic NaCl. HCO3(-)-secretion into the perfusate was titrated by the pH-stat technique. Stimulation of the vagal nerves increased gastric and duodenal HCO3(-)-secretions and these responses were blocked completely by hexamethonium and partly inhibited by atropine. Vagally induced increases in gastric and duodenal HCO3(-)-secretion were inhibited by: an intact splanchnic nerve supply, peripheral stimulation of the cut splanchnic nerves, and alpha-2-adrenoceptor stimulation with clonidine. In animals with intact splanchnic nerve supplies, the administration of the adrenolytic agent guanethidine or the alpha-2-adrenoceptor antagonist yohimbine revealed increases in gastric and duodenal HCO3(-)-secretion in response to vagal stimulation. Neither the alpha-1-adrenoceptor blocker prazosin nor the beta-adrenoceptor antagonist propranolol had any such effect. Furthermore, the inhibition of vagally induced gastric and duodenal HCO3(-)-secretion by splanchnic nerve stimulation or clonidine treatment was blocked by yohimbine. It can be concluded that peripheral autonomic nerves influence both gastric and duodenal HCO3(-) secretion. The vagal nerves convey an excitatory pathway involving nicotinic, as well as muscarinic, cholinoceptor-mediated transmission. Furthermore, the present data suggest the existence of a sympatho-inhibitory mechanism for which the primary point of action involves alpha-2-adrenoceptors, presumably at a neural site. PMID- 2880456 TI - [Effect of various catecholaminergic receptor agonists and blockaders on ethanol induced/sleep and hypothermia in mice]. PMID- 2880457 TI - Remoxipride in schizophrenia. A preliminary report. AB - Remoxipride, a substituted benzamide with preferential action on mesolimbic dopaminergic brain functions, was investigated in an open study in 10 schizophrenic patients. After 1 week with placebo, patients received remoxipride in a increasing doses from 150 to maximal 450 mg daily for 6 weeks. In six patients a clinically relevant reduction of psychotic symptomatology as assessed with the BPRS was observed. Few adverse effects were noted; extrapyramidal symptoms, if present, decreased during treatment, while the reported side effects were only mild. No consistent changes in plasma levels of prolactin and HVA were found. PMID- 2880458 TI - Oxypertine in tardive dyskinesia: a long-term controlled study. AB - A 6-month, double-blind, placebo-controlled study of oxypertine in tardive dyskinesia is described. Results suggest that any beneficial effect noticed initially is not sustained. When this effect is compared with the time course of development of supersensitivity after neuroleptics as reported in the literature, it becomes apparent that the drug, despite its different mechanism of action, behaves like any other conventional neuroleptic. On the basis of the findings, the authors feel that all proposed anti-dyskinetic drugs should be subjected to longer, controlled trials to prove their clinical efficacy. PMID- 2880460 TI - An experimental evaluation of the euphoric properties of antiparkinson drugs on psychotic patients. AB - Seven psychotic inpatients (two women and five men) aged between 18 and 74 years, treated with neuroleptic and antiparkinson drugs, participated in a double-blind study with 1/3 DDD (Defined Daily Dose) of procyclidine, orphenadrine, or trihexyphenidyl hydrochloride against placebo. Euphoric effects were scored on a self-rating scale and extrapyramidal side-effects on the Simpson-Angus rating scale at drug administration and 1, 3 and 6 h thereafter. With regard to euphoric effect, there was a significant (P less than 0.02) difference between start and end point (0 and 6 h) for placebo but not for the active antiparkinson drugs. There was no significant difference in extrapyramidal side-effects. No preference of drug was found, and it was not possible to recognize the patient's own drug among the tested drugs. Side-effects from the antiparkinson drugs were also measured prior to the administration. Five patients did not return to their earlier antiparkinson drugs after the study. PMID- 2880459 TI - Bromazepam and lorazepam in generalized anxiety: a placebo-controlled study with measurement of drug plasma concentrations. AB - Sixty outpatients with a diagnosis of generalized anxiety were randomly assigned to 4 weeks of treatment with bromazepam, lorazepam or placebo, following a 1-week placebo washout period. There was no significant difference in the anxiolytic effects of bromazepam and lorazepam, both of which were superior to placebo. However, lorazepam-treated patients tended to have a more depressed mood than those treated with bromazepam. Drug-treated patients had consistently less cognitive impairment than those treated with placebo, the difference being statistically significant (P less than .05) in the case of bromazepam. The most frequent side-effects reported with each drug were drowsiness, which tended to subside with time, and depression, which tended to emerge toward the end of the 4 week period. There was a positive correlation (r = 0.64) between age and bromazepam plasma concentration per unit dose, adjusted for weight, and a negative correlation (r = -0.50) between weight and lorazepam plasma concentration per unit dose, adjusted for age. PMID- 2880461 TI - Myocardial infarction--coronary care. PMID- 2880462 TI - Myocardial infarction--secondary prevention. PMID- 2880463 TI - Angina pectoris--medical treatment. PMID- 2880464 TI - P-fimbriated Escherichia coli in adults with renal scarring and pyelonephritis. AB - The commonest organism in urinary tract infections (UTI) is Escherichia coli. Pyelonephritogenic E.coli strains possess P-fimbriae which firmly attach to uroepithelial cells by recognition of a carbohydrate structure, alpha-D-Galp-(1 4)-beta-D-Galp, which is confined within all glycosphingolipids related to the human P-blood group antigens. Several investigators have studied virulence properties of E.coli and host resistance in relation to UTI. Uroepithelial cells from children and women with recurrent UTI have an increased capacity to bind E.coli. In contrast to previous studies the present one deals with patients with renal scarring, who constitute the major risk group among patients with UTI. P fimbriae mediated binding to uroepithelial cells was studied and the risk of recurrent UTI in patients with renal scarring was determined. Ninety per cent of the E.coli isolates from female patients with acute non-obstructive pyelonephritis in this study possess P-fimbriae (I). The fecal E.coli colonies obtained from these patients were P-fimbriated in 55% compared to 11% of the fecal E.coli colonies from healthy controls. The P-blood group distribution in 56 female patients with renal scarring and a history of febrile UTI was the same as in a control group of 39 healthy subjects (II). A history of recurrent and/or early infections did not increase the percentage of the P1 blood group phenotype. Forty-nine female patients with renal scarring were prospectively investigated for the incidence of symptomatic UTI in relation to fecal colonization with P fimbriated E.coli (III). Fifty-three per cent of the patients had altogether 65 episodes of symptomatic UTI during the three-year follow-up (0.036 infections per month). Eight patients (16%) had nine attacks of acute pyelonephritis and 4/5 of the tested E.coli strains from these patients were P-fimbriated. No relationship was demonstrated between the presence of P-fimbriated E.coli in the fecal flora and the development of subsequent acute pyelonephritis. The binding of P fimbriated E.coli to uroepithelial cells from 19 female patients with renal scarring was studied with the fluorescence-activated cell sorting (FACS) analysis (IV). The uroepithelial cells from the patients with renal scarring exhibited a significantly higher binding capacity (p less than 0.01) than uroepithelial cells from healthy controls. Furthermore, uroepithelial cells from the patients with renal scarring and kidney insufficiency had a higher availability of P-fimbriae receptors on their uroepithelial cells than cells obtained from patients with renal scarring and normal renal function (r = -0.75, p less than 0.001) (V).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2880465 TI - Implication of the spinal nucleus of the trigeminal nerve in acupuncture. AB - This voluminous nucleus extends from the upper part of the medulla oblongata to the 4th cervical segment of the spinal cord. This topography puts it in relation with numerous other spinal and cerebral centers = ventral and dorsal horns of the spinal cord, including spinal nucleus of the accessory nerve, nucleus solitarius, motor dorsal nucleus of the vagus nerve, reticular formation, etc... Even if the longitudinal aspect of this nucleus is not uniform, it must be pointed out that the three branches of the trigeminal nerve are represented along this course through the trigeminal spinal tract. These relations explain the straight reciprocal action of the nerve areas of the trigeminal branches with the first four cervical nerves and the related autonomic links. These direct elementary reflexes may explain: many referred symptoms; etiologic or triggering factors of neuralgias in the entire cervico-cephalic region; the treatment of the cervico cephalic diseases (of cerebrospinal or autonomic type) by stimulation of the various cervico-cephalic structures: acupuncture points, articular manipulations, massages, etc... an important part of auriculopuncture effects; the possibility to use points localized in various nerve areas to get the same action. PMID- 2880466 TI - Bio-electrical brain relations of pain and acupuncture effects on EEG spectral analysis in healthy volunteers. AB - Pain description and objective evaluation is difficult. In the last few years, a number of neuro-physiological methods have been used in the study of pain and acupuncture analgesia. EEG spectral analysis allows the description and objective quantification of brain bio-electrical activity changes. The present study aims at evaluating ischemic experimental pain, electroacupuncture (EA) and ischemic pain following EA on EEG spectral analysis in healthy volunteers. PMID- 2880467 TI - A comparison of laser acupuncture versus placebo in radicular and pseudoradicular pain syndromes as recorded by subjective responses of patients. AB - In a prospective randomized single blind cross over study the analgesic effects of laser irradiation on acupuncture points and a mock laser treatment (placebo) were compared in a sample of 21 patients suffering from radicular and pseudoradicular pain syndromes. Subjective pain levels were recorded on a visual verbal analogue pain rating scale before and after laser treatment and placebo along with the duration of any effects on pain observed. Mean pain levels after laser treatment were statistically significantly lower than after placebo (p less than 0.001, t-test). In the cross over section laser treatment was more effective than placebo in 20 out of 21 patients and pain relief lasted longer after laser treatment in 18 out of 21 patients. PMID- 2880468 TI - Omura's "Bi-Digital O-Ring Test" as a guide to acupuncture treatment. AB - Omura's "Bi-Digital O-Ring Test" is a valuable aid in the search for the site of pathology. We may use it also to confirm the acupuncture points to be used for treatment. This test provides excellent opportunity to test the immediate and long term results of our treatment, too. PMID- 2880469 TI - Re-evaluation of the classical acupuncture concept of meridians in Oriental medicine by the new method of detecting meridian-like network connected to internal organs using "Bi-Digital O-Ring Test". AB - "Bi-Digital O-Ring Test" has been successfully applied clinically as one of the simplest non-invasive, safe early diagnostic methods as well as localizing specific substances and neuro transmitters and tissues by the " 'Bi-Digital O Ring Test' Molecular Identification and Localization Method". Using the method most of the internal organs it becomes possible to image the outline of most of the internal organs on most of the body surface without exposing the patient to undesirable radiation of X-Ray or strong magnetic field. While imaging outline of the internal organs the author found that from the surface of each organ, lines or networks of lines extending to the other parts of the body. Such a line closely resembled classically well known lines of meridians of major internal organs in Oriental medicine which author named meridian-like network of each internal organ. Each internal organ's meridian-like network usually can be imaged using microscopic slide of tissue or tissue itself. However, entire part of the small intestine meridian in the arm can also be imaged by heart tissue. For example "spleen meridian" has been considered to represent mainly pancreas of the western medical concept and this was also confirmed by the fact that using microscopic slide of pancreas or dessicated tissue of the pancreas well-known spleen meridian-like network can be imaged. The author also confirmed some of the description of the direction of the meridian and direction of the in reference to the direction of the insertion of the acupuncture needle. The width of the line of this meridian-like network was usually within one or two millimeters and one millimeter outside of the line do not have the same characteristics. This meridian-like network seems to be specialized channel which can propagate some type of information in electro-magnetic field to regulate some of the body functions throughout the body which is difficult to explain in current western medical anatomical concept. PMID- 2880470 TI - The application of "Bi-Digital O-Ring Test" in the diagnosis and treatment of urinary tract infection in symptomatic and asymptomatic patients. AB - "Bi-Digital O-Ring Test" was used as the basis to diagnose abnormality in the urinary bladder, to detect the presence of infection, to choose the effective antibiotic for therapy, to follow up patients after treatment and to evaluate the therapeutic effect. Confirmation of urinary tract infection was done by using the "Bacturcult" urine culture system. This study of 45 patients reveals the value of "Bi-Digital O-Ring Test" in the early and inexpensive diagnosis and treatment of urinary tract infection. PMID- 2880471 TI - Practical clinical application of the Bi-Digital O-Ring Test in the diagnosis, treatment and follow-up of tuberculosis & parasitic infection. AB - Using the Bi-Digital O-Ring Test in three clinical cases where standard Western diagnostic methods were not satisfactory; successful diagnosis and treatment were made non-invasively, quickly and inexpensively with the Bi-Digital O-Ring Test. The three cases are as follows: Tuberculosis of the urinary tract; Pleural tuberculosis; Possible parasitic infection of the liver. PMID- 2880472 TI - Critical evaluation of Koryo Sooji Chim (Korean hand acupuncture) diagnosis by application of the Bi-Digital O-Ring Test. AB - The Bi-Digital O-Ring Test has been shown to be one of the most simple, non invasive early diagnostic methods, and its molecular and tissue identification method as well as food and drug compatibility test were applied for critical evaluation of Korean hand acupuncture diagnosis and treatment. The Bi-Digital O Ring Test confirmed the general validity of the concept of the Korean hand acupuncture diagnostic & therapeutic method. Omura's Bi-Digital O-Ring Test Malignant Tumor Identification Method, using microscopic slides of special types of malignant tissue of given internal organs was also found to be applicable to the organ representation areas of the hands and fingers. PMID- 2880473 TI - Acupuncture in the anesthetic management of eye surgery. AB - A study was conducted on twenty-four patients who underwent surgery for retinal detachment as to the clinical effect of acupuncture from the viewpoints of anesthetic dose, intraoperative changes in blood pressure and heart rate, postoperative analgesic state, nausea and vomiting. The patients were divided into two groups: group A, eleven patients receiving neuroleptanesthesia combined with acupuncture analgesia and group N, thirteen patients receiving usual neuroleptanesthesia without acupuncture. A significant difference was found in the dose of fentanyl, used as the narcotic, between group A (0.11 mg) and group N (0.48 mg). No difference was noted in blood pressure between the two groups, but it was high in group N in the postoperative period. There was no difference in heart rate between the two groups. Two patients from group A and five from group N required analgesics in the postoperative period. Nausea and vomiting were encountered in one patient in group A and three in group N. Therefore, it would seem that anesthesia in combination with acupuncture is capable of reducing the required dose of narcotic and offering more comfortable postoperative conditions than usual anesthesia alone. PMID- 2880474 TI - No synergism between metoclopramide and acupuncture in chronic pain. AB - Metoclopramide has in previous studies been found to be synergic with acupuncture analgesia both in the laboratory and in the clinics. In the present study no synergism could be shown when patients with chronic pain were treated with acupuncture. PMID- 2880475 TI - The 2nd International Symposium on Acupuncture & Electro-therapeutics. October 16 19, 1986, New York City. Program and abstracts. PMID- 2880476 TI - Regulation of hepatic ammonia metabolism: the intercellular glutamine cycle. AB - In the liver acinus, urea synthesis and glutaminase activity are predominantly localized in the periportal area, whereas glutamine synthetase activity is perivenous. Because ammonium ions at low concentrations are effectively removed by glutamine synthetase, but not by urea synthesis, the two pathways of ammonia detoxication in the liver acinus represent the sequence of a low-affinity, but high-capacity system (ureogenesis) and a perivenous high-affinity system (glutamine synthesis). In agreement with these findings, obtained in experiments with the metabolically and structurally intact perfused rat liver, perivenous glutamine synthesis was almost completely inhibited after induction of perivenous liver cell necrosis by carbon tetrachloride, whereas periportal urea synthesis was not affected. The structural and functional organization of hepatic ammonium and glutamine metabolism and the metabolic interactions of different subacinar hepatocyte populations provide a new understanding of hepatic nitrogen metabolism under physiological and pathological conditions. Periportal glutaminase and perivenous glutamine synthetase are simultaneously active, resulting in an intercellular (as opposed to intracellular) glutamine cycle, being under complex metabolic and hormonal control. The intercellular glutamine cycle provides an effective means for almost complete conversion of portal ammonium ions into urea without accompanying net glutamine formation. This is achieved by additional substrate feeding into the urea cycle by the glutaminase reaction, both pathways being localized in the periportal compartment, and the perivenous resynthesis of glutamine from ammonium ions which escaped periportal urea synthesis. This complete conversion of portal ammonium ions into urea by means of glutamine cycling represents the situation of a well-balanced pH homeostasis. Because urea synthesis, in contrast to glutamine synthesis, is a major pathway for removal of bicarbonate, the switching of hepatic ammonium detoxication from urea synthesis to glutamine synthesis in acidosis points to an important role of the liver in maintaining pH homeostasis. The acid-base-induced changes of the route of hepatic ammonium detoxication and therefore bicarbonate removal are performed by the regulatory properties of the enzymes of the intercellular glutamine cycle. PMID- 2880477 TI - Mechanism of action of glutathione-dependent enzymes. PMID- 2880478 TI - Active kallikrein, preprokallikrein, and kallikrein-inhibitor complex. AB - Active kallikreins isolated from various exocrine and endocrine tissues were identified by a monoclonal antibody in Western blot analyses to be approximately 38,000 dalton proteins. Kallikreins isolated from rat pancreas, kidney, submandibular gland, brain, spleen and urine were indistinguishable with respect to molecular weight and immunological characteristics. Preprokallikreins were synthesized in a cell-free translation system directed by mRNAs and immunoprecipitated by affinity-purified kallikrein antibody. Analysis of the precipitates by SDS-polyacrylamide gel electrophoresis revealed a approximately 37,000 dalton polypeptide in kidney, brain and submandibular gland translation products. This 37,000 dalton kallikrein precursor was hybrid-arrested by a kallikrein cDNA encoding tissue kallikrein which was isolated from a rat submandibular gland cDNA library. The immunoprecipitates of products directed by pancreatic mRNA showed a major protein with Mr of approximately 30,000. An endogenous approximately 92,000 dalton component in rat urine and kidney was also identified by a monoclonal antibody to tissue kallikrein and represents a kallikrein-inhibitor complex. These results indicate that tissue kallikreins can be initially synthesized as 37,000 or 30,000 dalton prepropeptides and then converted into a 38,000 dalton active form by proteolytic processing and glycosylation. The active kallikrein is capable of binding to an inhibitor to form a 92,000 dalton complex. PMID- 2880479 TI - Regulation of parotid kallikrein secretion-role of the alpha 2- and beta adrenergic system. AB - The effects of pharmacologically induced alterations of alpha 1, alpha 2 and beta adrenergic system on kallikrein secretion - measured as amidolytic activity - in rat parotid gland were tested in vivo. Beta and alpha 1/2-adrenergic stimulation (Orciprenaline, alpha-methylnorepinephrine) caused a comparably significant increase of parotid kallikrein secretion. Alpha 2-receptor blockade (yohimbine) but not the alpha 1-antagonist prazosin, partly abolished the effect of alpha methylnorepinephrine. The effects of the alpha 1-adreno-receptor agonist norfenephrine on kallikrein secretion were significantly lower compared to alpha 1/2-adreno-receptor-stimulation. PMID- 2880480 TI - Kinins, receptors, antagonists. AB - Kinins are potent myotropic agents acting on a variety of smooth muscle preparations: isolated arteries, veins, intestines, tracheae, urinary bladders, uteri, etc. In these tissues, kinins activate at least two different receptor types, B1 and B2. B1 and B2 receptors for kinins have been identified by measuring the order of potency of agonists and the affinities of specific and competitive antagonists. Results of pharmacological studies have been confirmed by several investigators using binding assays with labelled bradykinin (BK) or desArg9BK. Antagonists for kinins active on B1 and B2 receptors have been identified. Anti-B1 antagonists are specific, competitive and fairly potent: anti B2 antagonists have been identified among compounds primarily developed as anti tachykinins: these compounds are non-specific, non-competitive and rather weak. They however may provide interesting new pharmacological tools, active against both kinins and tachykinins, two groups of endogenous peptides involved in the inflammatory process. The type (direct, indirect) and the site (endothelial cell, smooth muscle fiber, autonomic nerve endings) of action of kinins in isolated vessels have been investigated. The results of various studies indicate that kinins do not act on the sympathetic nerve terminals of isolated organs in contrast with other peptides. Kinins do not promote the release of histamine or of 5-hydroxy-tryptamine from isolated arteries and veins. Kinins are equally active in the presence and absence of indomethacin (an inhibitor of cyclooxygenase) or of BW 755C (an inhibitor of lipoxygenase) in some organs, while the actions of kinins on other organs are reduced to a variable extent by these inhibitors. In general, B1 receptor systems do not depend on the activation of arachidonic acid, while B2 receptor systems do: activation of the arachidonic acid cascade may be a feature of B2 receptors. Stimulant effects of kinins on arterial or venous vessels are independent on the endothelium, while the relaxant effect on the dog carotid artery occurs only in vessels with intact endothelium. The mechanism of action of kinins and tachykinins appears to be different from that of acetylcholine, since the peptides effects are not influenced by BW 755C and ETYA, two inhibitors of lipooxygenase that reduce significantly the effect of acetylcholine. PMID- 2880481 TI - 3H-bradykinin binding site localization in guinea pig urinary system. AB - Bradykinin (BK) causes vasodilation and increases free water and sodium excretion in the kidney and stimulates smooth muscle contraction in the ureter and bladder. Several proposed sites of action for BK include the renal medullary collecting duct, renal blood vessels and the ureter and bladder smooth muscle. This study employs 3H-BK autoradiography to localize the sites of BK action. 3H-BK binding sites in the kidney are localized in the medullary interstitium where BK may produce prostaglandins which mediate its blood flow, natriuretic and diuretic effects. 3H-BK binding sites in the ureter and bladder are localized in the lamina propria below the basal epithelial layer and absent over the muscle layers suggesting an indirect action on urinary tract smooth muscle. PMID- 2880482 TI - The action of peptides and proteases on the arachidonate cascade of human and rat platelets. AB - The arachidonate cascade of human or rat platelets were found to be modified by peptides (bradykinin, angiotensin I, angiotensin II, Asp1-Val5-angiotensin II amide, somatostatin) and proteases (trypsin, kallikrein). The lipoxygenase pathway was not altered by angiotensin I, angiotensin II, trypsin and kallikrein, while the synthesis some of the cyclooxygenase products was selectively changed by these substances. Bradykinin and somatostatin resulted in an attenuated formation of 12-HPETE and 12-HETE - U shape dose response curve, at the same time the synthesis of cyclooxygenase metabolites was increased - bell shape dose response curve. Asp1-Val5-angiotensin II-amide increased the synthesis of lipoxygenase products and diminished the formation of TxB2. At the same time this peptide selectively induced the enzymatic release of PGD2 from platelets. These peptides and proteolytic enzymes might have physiologic significance in the "Ying Yang" balance in one hand between lipoxygenase and cyclooxygenase metabolites and on the other between the proaggregatory and antiaggregatory substances released from platelets. PMID- 2880483 TI - Enhancement of vascular permeability upon serratial infection: activation of Hageman factor--kallikrein--kinin cascade. AB - A zinc dependent serratial 56K protease caused enhancement of vascular permeability followed by edema formation when injected into the guinea pig peripheral cornea, the subconjunctival space, or the skin. Because this enhancement was not affected by antihistamine, involvement of the kinin generating system in this permeability enhancement was investigated. The 56K protease induced permeability much greater extent than that by bradykinin on weight basis, and more so on molar basis. The phenomenon was inhibited by soybean trypsin inhibitor, a well known inhibitor of plasma kallikrein, and also by corn trypsin inhibitor, which is the best inhibitor of the activated Hageman factor. In vitro experiments using numbers of synthetic peptide substrates, the 56K protease exhibited a similar substrate specificity to that of plasma kallikrein. Kallikrein is a known endogenous activator of Hageman factor. The enhancement by 56K protease was greatly augmented by inhibition of kininase II with Glu-Trp-Arg Pro-Gln-Ile-Pro-Pro-OH (SQ 20,881), suggesting generation of bradykinin. Thus, these results indicate that the enhancement of vascular permeability induced by the 56K protease is caused by an activation of Hageman factor by 56K protease followed by subsequent activation of cascade amplification, and resulted in kinin generation in vivo. PMID- 2880484 TI - The fimbrial adhesins of Escherichia coli. PMID- 2880485 TI - Eicosanoids in relation with LHRH secretion. PMID- 2880486 TI - [Urinary NAG and gamma-GTP activities as indicators of CDDP renal toxicity: effect of fosfomycin on CDDP renal toxicity]. AB - Using urinary N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma-GTP) activities as the indicator of renal toxicity, the effect of fosfomycin (FOM) on cisdichlorodiamineplatinum (CDDP) renal toxicity was studied in 10 patients with urological malignant tumors. Regimen of chemotherapy was daily 20 mg of CDDP and 800 mg of administered by drip infusion for 5 days and 40 mg of adriamycin injected in one-push on day 1. FOM was not used at 1st cure. At 2nd cure, daily 2 g X 2 of FOM was administered for eleven days from the day before CDDP administration. Urinary NAG and gamma-GTP were measured for eleven days continuously in both 1st and 2nd cure. Effect of FOM on CDDP renal toxicity was discussed by comparison of the urinary NAG and gamma-GTP activities between 1st and 2nd cure. The results showed that urinary NAG and gamma-GTP activities following CDDP administration were deeply influenced by these activities before CDDP administration and the combined therapy of FOM had tendency to reduce CDDP renal toxicity when urinary NAG and gamma-GTP activities before CDDP administration were in the normal range. PMID- 2880487 TI - [Neurogenic bladder with pituitary adenoma: report of two cases]. AB - Two cases of neurogenic bladder with pituitary adenoma are reported. The pituitary adenomas produced excessive GH (growth hormone). The etiology of the neurogenic bladder was not identified by X-ray examination or any other tests. Urodynamic study, however, indicated a functional cause of neurogenic bladder. Case 1 was a 55-year-old male, who had a relatively small pituitary adenoma with mild symptoms. Urologically, there was complete urinary retention. Cystometrogram showed a flaccid pattern, detrusor-sphincter dyssynergia in sphincter-EMG and ice water test was negative. Case 2 was a 67-year-old female, who had a large pituitary adenoma and severe symptoms. Cystometrogram showed an almost normal pattern, however, there was detrusor-sphincter dyssynergia and ice water test was negative. We suggested that the neuropeptide takes some part in the pathophysiologic cause of neurogenic bladder. PMID- 2880488 TI - Akathisia: the syndrome of motor restlessness. AB - Akathisia is a common but frequently unrecognized complication of antipsychotic medication. Affected individuals report an inner discomfort which they attempt to relieve by increased motor activity. This disorder often causes dramatic changes in behavior which may be misinterpreted as signs that more, rather than less, medication is required. Diphenhydramine therapy is often effective in new-onset akathisia. Anticholinergic agents may also be of value. PMID- 2880489 TI - Expectations of coronary artery surgery. AB - Coronary bypass surgery is now a well-established treatment for coronary artery disease. There is still controversy as to when surgery should be recommended. Taking into account a patient's age, coronary anatomy, degree of ischemia and left ventricular function, one can use available data to define the expectations for bypass surgery with reasonable accuracy. If important ischemia is present and the coronary anatomy is favorable, bypass surgery should improve the patient's quality of life and may significantly enhance survival. PMID- 2880490 TI - Acute myocardial infarction in post infarct patient possibly through beta blocker induced coronary artery spasm. PMID- 2880491 TI - Genetic regulation of apolipoproteins. PMID- 2880492 TI - The kidney and antihypertensive therapy. AB - To a large degree, modern antihypertensive therapy has evolved from the development of agents that act as vasodilators but, for one reason or another, avoid the disadvantages of the nonspecific vasodilators. This review examines the impact of antihypertensive agents on renal perfusion and function and relates it to their efficacy in reducing high blood pressure. Special attention is given to beta-adrenergic blocking agents that have a minimal impact on the kidney, converting enzyme inhibitors, calcium channel blockers and dopamine analogs. Also reviewed are the functional abnormalities involving the renal blood supply in essential hypertension, the role of newer pharmacologic agents in therapy and the nature and extent of reactive responses that often limit the response to therapeutic agents. PMID- 2880493 TI - Exercise and antihypertensive therapy. AB - The effects of exercise on central hemodynamic mechanisms and the changes induced by treatment have been studied invasively in approximately 500 men with essential hypertension. In patients with mild hypertension, the increase in blood pressure (BP) during dynamic exercise is similar to that seen in normal subjects, but in patients with severe hypertension it is steeper. During dynamic exercise total peripheral resistance is increased in all categories of hypertensive patients, including young subjects with apparently "normal" resistance at rest. The increase in stroke volume in transition from rest to exercise is subnormal, probably reflecting increased stiffness in the left ventricle. Static exercise causes dramatic increase in systolic as well as diastolic BP. Most antihypertensive agents control BP similarly during exercise and at rest. The hemodynamic mechanisms, however, differ greatly. The beta blockers induce a long term reduction in cardiac output, muscle blood flow and, frequently, endurance capacity. In contrast, alpha-receptor blockers, calcium antagonists and angiotensin converting enzyme inhibitors all reduce total peripheral resistance and do not decrease blood flow. Increase in endurance time has been reported with long-term calcium antagonist treatment. It would seem logical to select an antihypertensive drug that does not reduce exercise capacity when treating physically active patients with mild and moderate hypertension. PMID- 2880494 TI - Role of calcium antagonists in systemic hypertension. AB - Despite the physiologic rationale of their use in hypertension, traditional vasodilators such as hydralazine and minoxidil are often relegated to the second and, more often, to the third and fourth steps of step-care programs. Although they are powerful blood pressure-lowering agents, they cause tachycardia, excessive renin stimulation and sodium retention, and cannot be used as the only antihypertensive agent. The characteristics of the antihypertensive action of calcium antagonists make them suitable for monotherapy. Indeed, all calcium antagonists, while effectively lowering blood pressure through vasodilation, either do not affect heart rate (verapamil and its analogs) or cause a moderate and transient heart rate increase (dihydropyridine compounds). Dihydropyridines also possess a natriuretic effect, probably due to inhibition of tubular sodium transport. The natriuretic effect is evident during the first 2 days of administration, but a small negative sodium balance persists for at least 1 week. There is no increase in body weight or fluid volumes with long-term administration of calcium antagonists with a marked acute natriuretic response, such as dihydropyridines, and those antagonists with a very moderate immediate natriuretic response, such as verapamil. All calcium antagonists, therefore, appear capable of preventing the sodium and water retention that vasodilatation would otherwise entail. More liberal step-care guidelines are now possible to find the agent most suitable for the individual patient. In these guidelines, calcium antagonists, as well as angiotensin converting enzyme inhibitors, are considered as possible first-choice agents along with diuretics and beta blockers. PMID- 2880495 TI - Interaction between two calcium antagonists and two beta blockers in conscious rabbits: hemodynamic consequences of differing cardiodepressant properties. AB - The interaction between beta-adrenoreceptor blockers and calcium antagonists may occasionally be dangerous. The effects of the new calcium antagonist PN 200-110 (isradipine) were compared with those of verapamil in 3 groups of conscious rabbits pretreated with either pindolol 0.3 mg/kg, propranolol 1 mg/kg intravenously or placebo. Each animal received PN 200-110 (0.01, 0.03 and 0.1 mg/kg) and 2 or more days later verapamil (0.1, 0.3 and 1 mg/kg). The calcium antagonists were given to lower mean blood pressure to the same extent as in the placebo group. This blood pressure effect remained unchanged after pretreatment with pindolol or propranolol. Both PIN 200-110 and verapamil increased heart rate to the same extent as in the placebo group. Both beta blockers blunted the effect of PN 200-110 on heart rate but converted the verapamil-induced tachycardia to bradycardia. Propranolol blunted the PN 200-110-induced increase in cardiac output and total peripheral conductance, whereas the high verapamil dose decreased cardiac output and caused peripheral vasoconstriction in propranolol pretreated animals. Thus, both agents lowered blood pressure by peripheral vasodilatation in the placebo group, after beta blockade; however, the mechanism of the verapamil-induced blood pressure decrease changed from pure vasodilation to a decrease in cardiac output, i.e., cardiac depression. Verapamil but not PN 200-110 prolonged the PQ interval, especially in animals who had received beta blockade. Most differences in the interaction were attributable to differences between the 2 calcium antagonists; the differences between the beta blockers were small and in favor of pindolol. PMID- 2880496 TI - Calcium antagonists for chronic stable angina pectoris. AB - Stable angina pectoris classically occurs on exertion or in response to other well-defined stress, and can be treated successfully, both in regard to symptoms and ability to undertake more exertion, with available calcium antagonists. Numerous reports suggest that response to calcium antagonists is similar to that with beta-adrenergic blockers, although the latter tend to show somewhat greater efficacy. Advantages in favor of calcium antagonists include the relative freedom from side effects that may occur with beta-adrenergic antagonists; the 2 types of substances can be combined usefully and given to the vast majority of patients requiring medication for angina. Left ventricular failure is a relative contraindication to both calcium antagonists and beta-adrenergic blockers, and thus to the combination. With calcium antagonists, however, the negative inotropic effects are often balanced by the associated peripheral vasodilatation. Where medical management of chronic stable angina is considered, calcium antagonists offer a reasonable alternative to beta blockers, and the use of the combination is highly effective, more so than either substance alone. PMID- 2880497 TI - Spontaneous variability of ventricular arrhythmias in patients at increased risk for sudden death after acute myocardial infarction: consecutive ambulatory electrocardiographic recordings of 88 patients. AB - The Cardiac Arrhythmia Pilot Study, sponsored by the National Heart, Lung, and Blood Institute, is a multicenter, prospective, randomized, double-blind trial designed to identify patients having 10 or more ventricular premature complexes (VPCs) per hour within 6 to 60 days of acute myocardial infarction. The present investigation selected patients after acute myocardial infarction who had ambulatory electrocardiographic qualifying arrhythmia for CAPS. An additional baseline electrocardiogram was recorded before enrollment in the study to assess baseline spontaneous variability of VPCs. A total of 88 patients (15 women, 73 men, aged 57 +/- 10 years) were studied. The 43 patients (49%) receiving beta blocking drugs were included because the dose was not altered between the 2 consecutive electrocardiographic recordings. This investigation shows that a 95% reduction in VPCs is required to document a significant drug effect rather than variability alone if 1 day of control and 1 day of treatment electrocardiographic recording are compared. Similarly, based on 1 day of electrocardiographic recording before and after antiarrhythmic therapy, 1,780% increase in VPC frequency is required to establish "arrhythmia aggravation" from an antiarrhythmic drug rather than from variability alone based on a 95% confidence interval. Variability of ventricular arrhythmias is independent of left ventricular function, whereas patients taking beta-blocking therapy tend to have greater VPC variability (p = 0.052), even though VPC frequencies were lower (59 +/- 19 vs 138 +/- 31 VPCs/hour, p less than 0.006) than those not taking beta blocking drugs. PMID- 2880499 TI - Pluripotent hemopoietic stem cells give rise to osteoclasts. AB - Osteopetrosis in the ia (incisors absent) rat is the result of reduced bone resorption due to abnormal osteoclasts. The mutant osteoclasts lack a ruffled border--the membrane specialization involved in osteolysis. Studies in the ia mutant have shown that when pluripotent hemopoietic stem cells from normal littermates are transplanted into ia recipients, normal osteoclasts are formed and the skeletal sclerosis is eventually cured. The present study was conducted to provide evidence for the mechanism of the cure. Do the transplanted stem cells provide a helper function, i.e. secrete soluble factor(s) which transform pre existing osteoclasts, or do they fuse with each other or pre-existing osteoclasts, or do they fuse with each other or pre-existing osteoclasts to form functional osteoclasts? Using the procedures described by Gold-schneider and co workers, and fluorescence-activated cell sorting (FACS), pluripotent hemopoietic stem cells were isolated from normal rat bone marrow, labeled with saturated FITC, and injected intravenously into irradiated ia rats. After 48 hr, the recipients' long bones were removed and split longitudinally, and the endosteal surface was scraped. The resulting cellular suspension containing osteoclasts was examined by phase contrast and fluorescence microscopy. Fluorescing mononuclear cells of donor origin that had homed to the bone marrow demonstrated moderate cytoplasmic fluorescence. Approximately 30% of the osteoclasts observed demonstrated light cytoplasmic fluorescence. When cellular pools incapable of curing osteopetrosis (thymocytes) were labeled and injected into ia recipients, no labeled osteoclasts were observed. These studies indicated that pluripotent hemopoietic stem cells, when transplanted into ia hosts, fuse with each other and differentiate into osteoclasts or fuse with pre-existing osteoclasts. PMID- 2880500 TI - Attention deficit disorder is a chronic problem. PMID- 2880498 TI - Carvedilol for systemic hypertension. AB - Twenty-four-hour profiles of intraarterial ambulatory blood pressure (BP) and heart rate were significantly reduced by administration of carvedilol, a new beta blocking drug with vasodilating properties. Twelve patients were given carvedilol, 25 mg twice daily for 2 weeks; the dose was then increased to 50 mg twice daily if the target BP was not achieved. After 4 weeks of therapy, mean daytime reduction in BP was 25 +/- 3 mm Hg systolic and 19 +/- 3 mm Hg diastolic and mean reduction in heart rate was 22 +/- 3 beats/min. BP at the peak of isometric exercise and during dynamic exercise was also significantly reduced. Radionuclide measurements showed that left ventricular ejection fraction was not affected by treatment, but there was a significant reduction in systolic and diastolic volumes. The drug was well tolerated. This clinical trial suggests that carvedilol will be a useful first-line drug for treatment of essential hypertension, and its vasodilating action may have a more favorable effect on left ventricular function than conventional beta-blocking drugs. PMID- 2880501 TI - Regional residency cooperatives. PMID- 2880502 TI - Mortality experience of amosite asbestos factory workers: dose-response relationships 5 to 40 years after onset of short-term work exposure. AB - A cohort of 820 men in a Paterson, New Jersey, amosite asbestos factory which began work during 1941-1945 was observed from 5 to 40 years after start of work. Most of the cohort had limited duration of work experience (days, weeks, months), though some men worked for several years until the factory closed in 1954. With white males of New Jersey as the control population, Standardized Mortality Ratios (SMRs) of 500 are evident for the cohort for lung cancer and for noninfectious pulmonary diseases (including asbestosis), while being almost 300 for total cancer and about 170 for all causes of death. A statistically significant SMR of almost 200 is seen for colon-rectum cancer. Mesothelioma incidence initially shows a strong relationship with advancing time since onset of exposure and then tails off. The main concern of the study is with dose response patterns. Response is measured by the mortality for relevant causes of death, while the direct asbestos dosage was measured in two ways. One way was the length of time worked in the factory and the other was the individual's accumulated fiber exposure, calculated by multiplying the aforementioned length of time worked by the estimated fiber exposures associated with the particular job that the worker had in the factory. Whichever measure of dosage is used, it was found that, in general, the lower the dose, the longer it took for adverse mortality to become evident and, also, the smaller the magnitude of that adverse mortality. PMID- 2880503 TI - New therapeutic modalities for the treatment of elderly patients with ischemic heart disease. AB - In developing a treatment plan for elderly patients with ischemic heart disease, it is important to appreciate that the pathophysiologic process and aging influence the type of response produced by various drugs. The aging process also alters the way drugs are absorbed, distributed, and eliminated. Each of these variables must be considered in deciding which drugs should be used and how they should be administered. PMID- 2880505 TI - Coronary angioplasty of internal mammary artery graft. AB - The internal mammary artery is being increasingly utilized as a conduit for coronary artery bypass operations. Early stenosis of the mammary artery due to either surgical technique or early graft atherosclerosis is a problem that requires repeated bypass operations, with increased morbidity and mortality. Percutaneous transluminal coronary angioplasty appears to be an attractive therapeutic modality in the treatment of internal mammary artery graft stenosis and may be accomplished easily by either the femoral or brachial approach. Further follow-up studies are required to validate the long-term results of angioplasty of internal mammary artery grafts. PMID- 2880504 TI - Screening for alcohol abuse using the CAGE questionnaire. AB - A prospective study of 518 patients admitted to the orthopedic and medical services of a community-based teaching hospital during a six-month period was performed to test the hypothesis that a short, easily administered questionnaire would improve the detection rate by physicians of alcohol abuse. The CAGE questionnaire--a mnemonic for attempts to cut back on drinking, being annoyed at criticisms about drinking, feeling guilty about drinking, and using alcohol as an eye opener--was utilized as a screening instrument. The mean corpuscular volume of red blood cells, liver transaminase levels, and the gamma-glutamyl transpeptidase level were also evaluated as screening tests. The presence or absence of alcoholism and alcohol abuse for a consecutive sample of CAGE-negative patients and all patients answering "yes" to one or more of the CAGE questions was established through the administration of the Michigan Alcoholism Screening Test, a detailed chart review, and analysis of quantity of alcohol consumed. Diagnostic criteria were those described in the Diagnostic and Statistical Manual III. The prevalence of alcohol abuse was 20 percent. The mean corpuscular volume, gamma-glutamyl transpeptidase value, and liver transaminase levels were very insensitive as screening tests. In contrast, the CAGE questionnaire had a sensitivity of 85 percent and a specificity of 89 percent. Only 63 percent of the alcoholic subjects and alcohol abusers were detected by their physicians, and in only 24 percent of these cases did a physician address the problem with the patient. The CAGE questionnaire is a simple, sensitive, and specific screening test for alcohol abusers. PMID- 2880506 TI - Association between Takayasu's arteritis and cutaneous polyarteritis nodosa. PMID- 2880507 TI - Prenatal detection of intestinal obstructions, aneuploidy syndromes, and cystic fibrosis by microvillar enzyme assays (disaccharidases, alkaline phosphatase, and glutamyltransferase) in amniotic fluid. AB - Microvillar enzymes (disaccharidases, alkaline phosphatase, and gamma glutamyltransferase) were assayed in amniotic fluid from pregnancies with normal and abnormal fetuses to determine their specificity and reliability for the prenatal detection of intestinal obstructions and cystic fibrosis. All fetuses with imperforate anus, duodenal atresia, jejuno-ileal atresia, multiple intestinal atresia, or other forms of intestinal obstructions, with or without associated ventral wall defect or aneuploidy syndrome, showed diminished microvillar enzyme activities below the normal range of control amniotic fluid samples. The exclusively intestinal hydrolases maltase, sucrase, palatinase, and alkaline phosphatase were the most reliable and sensitive markers to detect intestinal obstructions whereas more widely distributed trehalase and gamma glutamyltransferase activities were less sensitive. The combination of intestinal disaccharidase maltase, sucrase or palatinase and ALP assays is more accurate for prenatal diagnosis of CF than a combination of intestinal ALP and GGTF assays. PMID- 2880508 TI - Drug strategies for airflow obstruction. PMID- 2880509 TI - Glutamine metabolism in rat skeletal muscle wounded with lambda-carrageenan. AB - Wounding with lambda-carrageenan results in a marked decrease in the intracellular-free glutamine content of rat skeletal muscle. The potential mechanisms for this finding, including alterations in glutamine release, glutamine utilization, and glutamine synthesis, were investigated in rats under pentobarbital anesthesia. Wounding did not increase glutamine release from muscle during incubation or isolated hindlimb perfusion. Wounded muscle utilized more glutamine than nonwounded muscle, as measured both by the production of [14C]O2 and of -glutamate from labeled glutamine. Maximal glutamine synthetase activity was increased by wounding. The increase in glutamine synthetase activity in wounded muscle was prevented by adrenalectomy and restored by replacement doses of corticosterone in wounded adrenalectomized animals. The decrease in muscle free glutamine induced by wounding is therefore not mediated by an increase in the release of this amino acid, nor by a reduction in the tissue capacity for glutamine synthesis, but by an increase in glutamine utilization at the site of injury. This difference is apparently determined by the utilization of glutamine by the cellular components of the inflammatory infiltrate, which were shown to be capable of active glutaminolysis. PMID- 2880510 TI - Acute metabolic effects of adrenergic agents in swine. AB - A pig model in vivo was used to confirm the unique specificity for stimulation of porcine adipose tissue lipolysis by norepinephrine analogues in vitro. Plasma free fatty acid and blood glycerol concentrations were monitored as probable indicators of adipose tissue lipolysis. Plasma glucose and lactate concentrations, blood pressure, and heart rate were monitored also. Norepinephrine analogues were infused intravenously. Several compounds, classified as either beta 1- or beta 2-adrenergic agonists, that stimulated lipolysis in vitro also increased plasma free fatty acid and blood glycerol concentrations in vivo. Tazolol (beta 1) and quinterenol (beta 2) did not stimulate lipolysis in vitro and likewise did not elevate plasma free fatty acid or blood glycerol concentrations in vivo. Clenbuterol and zinterol did not stimulate lipolysis in vitro but elevated plasma free fatty acid concentrations in vivo, implying indirect effects. Isoproterenol stimulation of plasma free fatty acid and blood glycerol concentrations in vivo was antagonized by propranolol, implying the beta-adrenergic nature of the receptors. Infusion of purported beta 1- and beta 2-adrenergic antagonists suggested control of lipolysis in vivo predominantly by beta 1-adrenergic receptors; however, because the results in vitro do not indicate this specificity, differential pharmacodynamics of the antagonists are suggested rather than designation of receptor subtypes. There was no evidence for alpha-adrenergic mediated inhibition of adipose tissue lipolysis in vivo, confirming observations in vitro. PMID- 2880511 TI - Transport of acidic amino acids by human jejunal brush-border membrane vesicles. AB - This study characterizes the transport of radiolabeled acidic amino acids into brush-border membrane vesicles prepared from human jejunum. The uptakes of L glutamic, L-aspartic, and D-aspartic acids were stimulated by a Na+ gradient (extravesicular greater than intravesicular). Concentrative uptake (resulting in an "overshoot" phenomenon) of these dicarboxylic amino acids occurred when there was an outward K+ gradient (intravesicular greater than extravesicular). In addition, increasing K+ gradients (0-100 mM) resulted in enhanced uptake of L glutamic acid. This K+ requirement is somewhat specific as Rb+ and Cs+ could enhance uptake to a limited extent, whereas Li+ and choline+ showed no enhancement. The presence of a K+ gradient did not affect the affinity of the carrier system for L-glutamic acid but it did increase the Vmax. The presence of extravesicular anions having differing membrane permeabilities did not alter L glutamic acid uptake indicating an absence of an effect of membrane potential on the transport process. Finally, the human transport system for L-glutamic acid appears to be specific for acidic amino acids as demonstrated by inhibition studies. Our studies demonstrate a transport system in human jejunum specific for acidic amino acids that is energized by an inward Na+ gradient and an outward K+ gradient. PMID- 2880512 TI - Vagal cold block in area postrema-lesioned dogs: interaction of vasopressin and sympathetic nervous system. AB - This study evaluated the interaction between arginine vasopressin (AVP) and the sympathetic nervous system (SNS) during bilateral vagal cold block (BVB) and the arterial baroreflex response to phenylephrine (PE) and exogenous AVP in conscious sham-operated (sham) and area postrema (AP)-lesioned mongrel dogs. The hemodynamic responses to ganglionic blockade (GB) and the vascular (V1) AVP receptor antagonist [d(CH2)5Tyr(Me)]AVP (AVPX) were similar in sham and AP lesioned dogs. Elimination of the AVP pressor system by AVPX in sham dogs did not alter the pressor response to BVB, whereas subsequent blockade of the SNS by GB abolished the response to BVB. When GB was first imposed, however, it alone eliminated only 55% of the pressor response to BVB, whereas subsequent AVPX eliminated the remaining pressor response to BVB. In contrast, in AP-lesioned dogs, AVPX alone substantially reduced the pressor response to BVB. Additionally, the apparent contribution of each pressor system to the response to BVB was not enhanced in the absence of the other system, as had been seen in the sham dogs. These data indicate that during interruption of vagal afferent activity, reflexly released AVP appears to limit the reflex activation of the SNS. This interaction of AVP with the cardiopulmonary reflex is eliminated following ablation of the area postrema. Infusion studies with PE and AVP indicate that AVP significantly augments baroreflex inhibition of heart rate when compared with PE. Ablation of the area postrema did not alter the arterial pressure-heart rate relationship obtained with PE but eliminated the augmented response to AVP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2880513 TI - Renal metabolism of amino acids in vivo: studies on serine and glycine fluxes. AB - The pathway of serine synthesis by the rat kidney has been investigated in vivo by measuring the net flux in the presence and absence of specific inhibitors of the glycine cleavage system, phosphoenol-pyruvate carboxykinase and gamma glutamyltranspeptidase. In normal animals serine release was 705 +/- 187 nmol X min-1 X animal-1, whereas glycine uptake was only 28% of this value. Inhibition of the glycine cleavage system (cysteamine infusion) resulted in a reversal of glycine flux with no change in serine production. In similar experiments with mercaptopicolinate serine release was decreased by 55% with no change in glycine removal. AT-125, a potent inhibitor of gamma-glutamyltranspeptidase, had no effect on renal serine and glycine fluxes. In chronically acidotic rats serine synthesis was unchanged, but there were significant increases in the uptake of glutamine (fourfold) and glycine (2.5-fold). Infusion of cysteamine into these animals caused a 50% decrease in serine release with a significant reversal of the glycine flux. Infusion of mercaptopicolinate had effects similar to those observed in normal animals. These results show that renal serine synthesis can occur by both the phosphorylated-intermediate pathway and serine hydroxymethyltransferase in vivo. Furthermore, they demonstrate that glycine can contribute significantly to ammoniagenesis during acidosis. PMID- 2880514 TI - Effects of cardiac sympathetic nerve stimulation on regional coronary blood flow. AB - The purpose of this study was to examine the effects of cardiac sympathetic nerve stimulation on regional coronary blood flow following beta-blockade. In 17 anesthetized dogs treated with propranolol (2 mg/kg iv) regional myocardial perfusion was measured (microspheres) during control and during stimulation of the ventrolateral, ventromedial, or recurrent cardiac nerve (8-10 V, 4-ms pulses at 10 Hz for 30 s). Ventrolateral nerve stimulation produced 25.5 +/- 3.4 and 23.5 +/- 3.1% (mean +/- SE) decreases in coronary blood flow in the posterior and lateral quadrants of the left ventricle. These changes were significantly greater than the 8.5 +/- 2.9, 11.5 +/- 3.0, and 3.7 +/- 2.8% decreases in the anterior and septal left ventricle and right ventricle, respectively (P less than 0.01). Ventromedial nerve stimulation produced 18.6 +/- 2.8, 15.4 +/- 2.8, and 10.1 +/- 3.2% decreases in flow in the anterior, septal, and lateral left ventricle, respectively. These changes were significantly greater than the 5.3 +/- 3.8 and 9.9 +/- 3.6% decrease in the posterior left ventricle and right ventricle (P less than 0.01). Recurrent cardiac nerve stimulation produced 16.4 +/- 2.1, 15.6 +/- 2.2, and 13.6 +/- 2.5% decreases in flow in the anterior and septal left ventricle and right ventricle, respectively. These changes were significantly greater than the 5.2 +/- 3.2 and 5.4 +/- 3.0% changes in the posterior and lateral quadrants (P less than 0.01). Ventrolateral nerve stimulation resulted in a small but significant increase in the endocardial-to-epicardial blood flow ratio in the posterolateral left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2880515 TI - Cardiovascular and endocrine response to hemorrhage after alpha 1-blockade in lambs and ewes. AB - To evaluate the role of the alpha 1-adrenergic system in the response to hemorrhage during development, lambs and adult sheep were chronically catheterized and hemorrhaged after pretreatment with prazosin or vehicle. The adults became markedly more hypotensive after alpha 1-blockade and hemorrhage than after vehicle and hemorrhage (26.1 +/- 4 vs. 10.7 +/- 2%, P less than 0.0001), whereas the lambs were no more hypotensive when hemorrhaged after prazosin (21.5 +/- 3.2 vs. 23.1 +/- 4.4%, P greater than 0.05). In the adults and the lambs, hemorrhage produced elevations in plasma renin activity and arginine vasopressin. However, after prazosin, the adults had a far greater increase in arginine vasopressin levels than after vehicle treatment (1,970 +/- 820 vs. 320 +/- 273%). PMID- 2880516 TI - Clonidine in neuroleptic-induced akathisia. AB - Six hospitalized patients with neuroleptic-induced akathisia were treated with clonidine under single-blind conditions. Akathisia and anxiety at maximum clonidine dose were significantly lower than at baseline, although it was difficult to differentiate specific therapeutic effects from sedation. PMID- 2880517 TI - Tardive dyskinesia: a serious side effect? PMID- 2880518 TI - Lithium and extrapyramidal side effects of neuroleptics. PMID- 2880519 TI - The endocrine cells of the digestive tract. General concepts and historic perspective. AB - The chromaffin cells of the digestive mucosa were discovered by Heidenhain in 1870, long before the hormone concept was formulated. Following the discovery of the first hormone, secretin, by Bayliss and Starling in 1902, the study of the cells producing such messengers acquired new impetus. After Masson, in 1914, showed that the digestive chromaffin cells were argentaffin and suggested their endocrine nature, a series of technological advances led to the gradual characterization of diverse cell types, their classification, and the discovery of their function. Histochemistry, including silver impregnations, fluorescence microscopy, and aniline stains, exposed the complexity of the digestive endocrine cells. Electron microscopy provided structural markers for their characterization and the basis for the formulation of the first universally accepted classifications. Light- and electron-microscopic immunocytochemistry contributed to the understanding of the function of many of these cells, thus opening the way for modern classifications. Many unsolved problems still remain. These include the existence of cells without defined function, of chemical messengers without known cell of origin, and the presence of multiple messengers in some cell types. Answers are expected to emerge from further application of immunocytochemistry and from the introduction of modern approaches, such as in-situ hybridization histochemistry. PMID- 2880520 TI - Hyperplastic lesions of the gastrointestinal endocrine cells. AB - A substantial body of knowledge is presently available on the morphologic, histochemical, ultrastructural, and functional characteristics of both the normal endocrine cell population of the gut and their related endocrine tumors. In contrast to this, we have only recently begun to recognize the existence of hyperplastic proliferations of various endocrine cell types, and information is therefore steadily accumulating on the morphologic criteria for their recognition, their clinicopathologic correlates and the clinical relevance of this morphologic finding. Hyperplastic proliferations of various endocrine cell types most often develop as a secondary phenomenon in a variety of clinical situations, and may modify the clinical course of the associated condition in a manner that underscores the functional interrelationships these endocrine cells have not only with each other but with other cell types as well. However, similar proliferations may also occur as a primary event (e.g. primary antral G-cell hyperplasia) and give rise to clinical and biochemical features attributable to the overproduction of their specific hormonal product (e.g. Zollinger-Ellison Syndrome, type I). This communication provides a broad overview of the current state of our knowledge of hyperplastic lesions of a variety of gut endocrine cell types in humans, their pathophysiologic significance, their relationship (if any) to the subsequent development of endocrine tumors (i.e. the hyperplasia-neoplasia sequence), and the utility of certain experimental models for the study of such proliferations in a variety of animal species. PMID- 2880521 TI - Arbovirus isolations from mosquitoes collected during and after the 1982-1983 epizootic of western equine encephalitis in Argentina. AB - Mosquitoes were collected in Santa Fe and Rio Negro provinces, Argentina, in 1982 1983 during a western equine encephalitis (WEE) epizootic. Totals of 153,084 mosquitoes from Santa Fe Province and 484 from Rio Negro Province were tested for virus in 2,351 pools. Seventeen virus strains were isolated, all from Santa Fe collections, as follows: 4 WEE, 6 Venezuelan equine encephalitis, 1 St. Louis encephalitis, 2 Antequera, 1 Maguari, 1 Melao, 1 new vesiculovirus (Calchaqui), and 1 Gamboa. The WEE virus isolates were from Aedes albifasciatus, Anopheles albitarsis, Mansonia species, and Psorophora pallescens. Collections during the spring and summer (1983-1984) following the epizootic yielded 49,707 mosquitoes from Santa Fe, 15,961 from Rio Negro, and 2,019 from Chubut provinces. Twenty-two virus strains were isolated, all from Santa Fe mosquitoes, as follows: 3 strains of SLE virus and 19 strains of Turlock (TUR) virus. All but one of the TUR virus isolates appear to have come from mosquitoes that engorged on a viremic chicken following entry into a bait trap. The vector relationships of each virus isolated during and after the WEE epizootic are discussed. PMID- 2880523 TI - Conventional and coming laboratory markers of alcoholism and heavy drinking. PMID- 2880522 TI - A newly recognized vesiculovirus, Calchaqui virus, and subtypes of Melao and Maguari viruses from Argentina, with serologic evidence for infections of humans and horses. AB - In 1983, 17 virus strains were isolated from mosquitoes collected during an outbreak of western equine encephalitis in Santa Fe Province, Argentina. Strains of western equine encephalitis, Venezuelan equine encephalitis, St. Louis encephalitis, and Antequera viruses were isolated, as were several bunyaviruses of the California and Bunyamwera serogroups and a new vesiculovirus. Complement fixation and neutralization tests were used to identify the California serogroup virus as a subtype of Melao virus, the Bunyamwera serogroup virus as a subtype of both Maguari and Playas viruses, and the vesiculovirus as a newly recognized agent for which the name Calchaqui virus is proposed. A limited serosurvey of horses and humans in Santa Fe Province and horses from the adjacent Santiago del Estero Province was performed to determine the prevalence of neutralizing antibody to the subtypes of Melao and Maguari viruses and to Calchaqui virus. The high prevalence of antibodies to these three agents indicates the need for further studies of their disease potential in horses, because they are closely related to several other viruses that are known equine pathogens. PMID- 2880524 TI - Vecuronium and phaeochromocytoma. A report of two cases using different modes of administration. AB - Two patients presenting for removal of phaeochromocytoma are described. Vecuronium was used to provide neuromuscular blockade by two different methods of administration: an infusion and a large bolus dose. Both gave satisfactory results and we suggest that vecuronium may be the neuromuscular blocking agent of choice for patients with phaeochromocytoma. PMID- 2880525 TI - [The pharmacodynamics of vecuronium on the musculature of the vocal cords and the ball of the thumb. Preliminary report]. AB - During endolaryngeal microsurgery, an attempt was made to quantify laryngeal muscle relaxation by electromyographic recording of evoked responses from the vocal cord musculature in 5 patients. Both mechanographic and electromyographic recordings from the adductor pollicis were obtained simultaneously. Following a bolus dose of vecuronium (60 micrograms/kg, n = 3, and 100 micrograms/kg, n = 2), nearly total (97%-100%) suppression of evoked responses at the peripheral muscle site was observed; the vocal cords, however, did not show complete neuromuscular (nm) blockade, but rather varying degrees of nm depression ranging from 61%-92%. The present results clearly show that quantitative information as to duration and degree of neuromuscular depression in the vocal musculature may be obtained by electromyographic recordings of evoked potentials in the clinical setting; it is impossible however, to quantitatively estimate the extent of intrinsic laryngeal muscle relaxation from peripheral nm depression. The pharmacodynamic differences observed might be due to the varying acetylcholine receptor density of the muscle groups studied. PMID- 2880526 TI - Radiation inactivation probe of membrane-bound enzymes: gamma glutamyltranspeptidase, aminopeptidase N, and sucrase. AB - gamma-Glutamyltranspeptidase (GGT), aminopeptidase N (AP-N), and sucrase in purified rabbit intestinal brush border membrane vesicles were irradiated in situ at -135 degrees C using high energy electrons. Surviving activities of the enzymes were measured as a function of radiation dose, and the functional unit target sizes (corresponding to carbohydrate-free polypeptides) were determined using target analysis. The in situ functional unit sizes were GGT 59 kDa, AP-N 59 kDa, and sucrase 63 kDa. Together with biochemical data determined previously, it is concluded that the noncovalently attached large (approximately 40 kDa) and small (approximately 25 kDa) subunits of GGT are both required for catalytic activity. Furthermore, these data suggest that (i) the membrane-bound form of AP N consists of one or more noncovalently attached subunits of 59 kDa, each of which is enzymatically active; and (ii) in situ sucrase activity is associated with a subunit of 63 kDa which is noncovalently attached within the sucrase isomaltase complex. PMID- 2880527 TI - Selectivity and sensitivity improvements at perfluorinated ionomer/cellulose acetate bilayer electrodes. PMID- 2880528 TI - Distribution of gamma-glutamyl transpeptidase in male reproductive system of rats and its age-related changes. AB - The present study is designed to investigate localization of gamma-glutamyl transpeptidase (gamma-GTP) in male reproductive organs and its age-related changes using Wistar rats aged 2 to 15 weeks. Histochemically, gamma-GTP activity was detected intensively in epithelial cells of epididymides and seminal vesicles and weakly in those of anterior prostates, but not in testes under the present conditions. Biochemically, the highest gamma-GTP activity was found in epididymal head portions. The order of the activity was epididymides (head greater than body greater than tail), seminal vesicles, prostates and testes. The activity increases with sexual maturation in epididymides and seminal vesicles, but not in prostates. Since gamma-GTP is an enzyme involved in the incorporation of amino acids, the present findings suggest that not only epididymides but also seminal vesicles possess uptake mechanisms for amino acids. PMID- 2880529 TI - The neuromuscular blocking effect of vecuronium on the human diaphragm. AB - This study compares the neuromuscular blocking effect of vecuronium (0.1 mg/kg) on the diaphragm and the adductor pollicis in nine anesthetized patients. Monitoring of the diaphragm consisted of measurement of the transdiaphragmatic pressure after bilateral phrenic nerve stimulation. Onset time for neuromuscular blockade of the diaphragm was 1.6 +/- 0.3 min (+/-SD) compared to 2.5 +/- 0.3 min in the adductor pollicis (P less than 0.001). The diaphragm recovered earlier and more rapidly than the adductor pollicis. The twitch height (TH) returned to 25% of its control value after 27 +/- 8 min for the diaphragm, compared to 41 +/- 11 min for the adductor pollicis (P less than 0.01). Complete TH recovery was achieved after 49 +/- 14 min for the diaphragm and after 74 +/- 22 min for the adductor pollicis (P less than 0.01). The recovery index of 12 +/- 4 min for the diaphragm was significantly shorter (P less than 0.05) than for the adductor pollicis (20 +/- 9 min.) We conclude that monitoring of peripheral muscles in anesthetized patients given vecuronium provides adequate information about the degree of paralysis of the diaphragm. PMID- 2880530 TI - Hemodynamic effects of esmolol in chronically beta-blocked patients undergoing aortocoronary bypass surgery. AB - The hemodynamic effects of esmolol were studied in 40 patients scheduled for elective coronary artery surgery to determine whether the administration of esmolol in chronically beta-blocked patients would result in additional attenuation of sympathetically mediated hemodynamic stress responses to noxious stimuli. Patients were randomly assigned to receive IV infusions of esmolol or 5% dextrose in water (D5W). All received their regular dose of beta-adrenergic blocker within 6 hr of surgery and were anesthetized with diazepam, pancuronium, and enflurane. Increases (greater than 25% above baseline) in systolic blood pressure were treated with sodium nitroprusside (SNP). Esmolol was started before induction of anesthesia and continued until 5 min after maximal sternal spread. There were no statistically significant differences between the esmolol and control groups in any hemodynamic parameter during induction, intubation, skin incision, and sternotomy. Only at 5 min after maximal sternal spread was there a statistically significant lower systolic blood pressure in the esmolol-treated group. However the incidence and magnitude of SNP use in the control group was significantly (P less than 0.05) greater. Thus, the lower blood pressure, in the absence of changes in systemic vascular resistance, cardiac index, heart rate, and pulmonary capillary wedge pressure points toward a decrease in myocardial contractility, suggesting that the addition of esmolol to chronically used beta blockers resulted in an additional negative inotropic effect. We conclude that in patients with coronary artery disease in whom chronic beta-blocker therapy is continued until the time of surgery, esmolol does not further attenuate the heart rate response but does attenuate the increase in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2880531 TI - Prolonged neuromuscular paralysis with vecuronium in a patient with polymyositis. PMID- 2880532 TI - Direct effects of H2-receptor antagonists on airway smooth muscle and on responses mediated by H1- and H2-receptors. AB - Because it has been suggested that histamine H2-receptor antagonists may worsen airway constriction in asthmatic patients, we investigated the comparative effects of three histamine H2-receptor antagonists on guinea pig tracheal smooth muscle in vitro. When tested against resting tone, cimetidine, ranitidine and famotidine produced dose-related relaxation with pD2 values (negative log of ED50 for relaxation) (+/- SE, n; eq 5) of 3.20 +/- 0.04, 2.95 +/- 0.16 and 2.97 +/- 0.14, respectively. Concentrations that were below threshold for relaxation, did not elicit contraction. However, when the preparations were precontracted with histamine (10(-5)M), dose-response curves for relaxation were shifted to the right, and low-concentrations of all three histamine H2-antagonists augmented histamine-induced tone. When preparations were pretreated with cimetidine (10(-6) to 10(-4) M) and then tested for sensitivity to histamine, dose-response curves for histamine-induced contraction were shifted to the left (potentiated). These results provide further evidence for a modulatory effect of airway H2-receptors on the contractile response to histamine. In addition, since the concentrations associated with potentiation of histamine-induced contraction were about the same for all three H2-receptor antagonists (greater than or equal to 10(-5) M), our studies suggest a greater likelihood of airway constriction for the less potent H2-receptor antagonists that must be administered in higher clinical doses. PMID- 2880533 TI - [The cardiovascular system and adrenergic inhibition]. PMID- 2880534 TI - Acute titration and chronic follow-up with captopril in hypertension. A one-year safety profile on combination therapy with captopril and a diuretic. AB - The present study examines acute titration with captopril and chronic follow-up data on captopril and a diuretic in patients with all forms of hypertension. Captopril was initiated in those patients in whom previous antihypertensive agents either failed to control high blood pressure or produced adverse reactions. Acute titration was done in 88 patients in whom average diastolic blood pressure was equal to or more than 95 mm Hg. Initial titration dosage was decided on the basis of initial blood pressure recordings. During initial titration, 5 patients received 12.5 mg, 51 received 25 mg, 28 received 50 mg, and the remaining 4 received 100 mg of captopril. Post-captopril blood pressure data were normalized by using pre-captopril data as 100% for each patient. The blood pressure-lowering effect of captopril on both systolic and diastolic blood pressure in all 88 patients was statistically significant (p less than 0.05), within forty-five minutes of captopril administration irrespective of the doses. No adverse reactions were seen during the acute titration. After the initial titration, in all 88 patients a diuretic was added to obtain a synergistic effect. Eleven patients were dropped from the study, for they could not follow the requirements of the protocol. In 77 patients the data for a one-year safety profile with captopril and diuretic were available. There were no overall significant statistical changes in serial white blood cell count, serum potassium, and serum creatinine values in those 77 patients. In 31 patients the initial and maintenance dosage of captopril and the diuretic remained unaltered for one year. Post-captopril blood pressure and heart rate data were normalized, pre-captopril data being considered as 100% in those 31 patients. The blood pressure data following captopril and a diuretic therapy compared with the pre captopril data were statistically significant (p less than 0.05) throughout the study period. However, no significant changes in heart rates were observed during the study period. In all other patients, diuretic therapy was continued throughout the study period. In 6 severely hypertensive patients, an additional beta-blocker was needed for further control of high blood pressure. In 3 severe hypertensives with renal failure, besides a diuretic and a beta-blocker, minoxidil was needed to normalize their high blood pressure. In 4 of 77 patients, verapamil was used for treatment of either vasospastic angina or paroxsysmal supraventricular arrhythmia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2880535 TI - Platelet function in patients admitted with a diagnosis of myocardial infarction. AB - Platelet function and thromboxane A2 release were measured in 71 patients admitted to a coronary care unit with a provisional diagnosis of acute myocardial infarction (AMI). All measurements were carried out within twenty-four hours of admission. Of these, 35 patients had the diagnosis of AMI confirmed. The remainder (n = 36), who did not have AMI (NMI), were divided into two groups: those (n = 18) with an unequivocal history of previous vascular disease and those without vascular disease (n = 18). Platelet aggregation and thromboxane A2 (TXA2) release were significantly increased in the AMI group when compared with those in the NMI without vascular disease group or a healthy control group with similar age and sex distribution. Aggregation and TXA2 release in the NMI patients with vascular disease were greater than those in controls and did not differ significantly from those in the AMI group. Patients in the AMI or NMI with vascular disease groups who were taking beta-blockers or calcium channel antagonists at the time of admission showed significantly less platelet aggregation than those who were not taking these drugs. Heparin, added in vitro at therapeutic concentrations, induced significantly more aggregation in patients in the AMI and NMI with vascular disease groups than in the NMI without vascular disease group. We conclude that: platelets obtained from patients with AMI are hyperaggregable and release more TXA2; platelets from patients with significant vascular disease are hyperaggregable, even in the absence of AMI, although they are not as hyperaggregable as those from AMI; treatment with nifedipine and beta blockers protects these patients from platelet hyperaggregability; heparin induces significant aggregation of platelets from patients with AMI and NMI with vascular disease. These observations are of importance in considering the pathogenesis and treatment of AMI and ischemic heart disease. PMID- 2880536 TI - Non-Hodgkin lymphoma in Jamaica and its relation to adult T-cell leukemia lymphoma. AB - Of 95 patients consecutively diagnosed with non-Hodgkin lymphoma, 52 (55%) had antibodies to human T-cell leukemia-lymphoma virus, type I. Antibody positivity was strongly associated with skin involvement, leukemia, and hypercalcemia (p less than 0.02). Two patients had systemic opportunistic infections. Neither meningeal nor lung infiltration was detected, and lymph node infiltration was diffuse in all patients. Of 36 patients who received immunophenotypic classifications, 30 had diseases that affected the T-cell system, and the cells of all tested patients with these diseases showed the helper/inducer (T4) phenotype. Twenty-seven of these thirty-six patients were found to have adult T cell leukemia-lymphoma, and of the 27, 24 had antibodies to HTLV-I. The median duration of survival in patients with adult T-cell leukemia-lymphoma was 17 weeks, but a subgroup of 9 patients had indolent courses and a median survival of 81 weeks, which suggests that the disease has differing expression with courses that range from smoldering and indolent to acute and rapidly fatal. Hypercalcemia was the most important prognostic determinant of adult T-cell leukemia-lymphoma. PMID- 2880537 TI - Amyl and butyl nitrites and telangiectasia in homosexual men. PMID- 2880538 TI - [Endocrine paraneoplastic syndromes of primary bronchial cancers]. PMID- 2880539 TI - [Role of corticoids, immunosuppressive agents and plasma exchange in the treatment of systemic necrotizing angiitis]. PMID- 2880540 TI - [Depersonalization, Cotard's syndrome and tendency toward mania under benzodiazepine (apropos of 2 case reports)]. PMID- 2880541 TI - [Systematized treatment of patients hospitalized with anorexia nervosa]. AB - In-patients with anorexia nervosa are generally treated by two behavioral techniques such as desensitization and operant conditioning. In this work, functional analysis enables a better clinical description of the disorders allowing more specific therapeutic measures. Three patients have been treated according to this procedure. Return to normal of many behavior disorders like quantitative and qualitative restriction of food intake, vomiting and bulimia, has been confirmed by self evaluating measurement. The authors discuss the persistence of body image disturbances, and the need for the association of a cognitive approach. PMID- 2880542 TI - [Efficacy of low doses of atypical neuroleptics (benzamides) in defect states]. AB - Recently many authors have hypothesized that the desinhibitory property of some neuroleptics at low doses might be related to the activation of the dopaminergic system and that, on the contrary, the overactivity of dopaminergic functions could underly the productive symptoms of some schizophrenic states. In order to test this bipolar hypothesis two independent controlled studies were set up using the same new benzamide compound (amisulpride) at different doses in the opposite forms of schizophrenia. According to the results of these studies there are evidences to sustain the assertion that amisulpride at low doses is efficient in negative symptoms of schizophrenia such as poverty of ideation, flattening of affect, inattention, asociality and that the same compound at high doses is also efficient in productive forms of schizophrenia. Whether this bipolar activity is due to the play of different kinds of receptors according to the dosage used, or is due to the dopaminergic blockade in different brain areas related to the dosage remains a problem to be solved. PMID- 2880543 TI - [The role of a mediator object in the initial analytic therapy of psychotics]. PMID- 2880545 TI - Technology assessment at the National Institute of Child Health and Human Development: an alternative model. PMID- 2880544 TI - Application of molecular and somatic cell genetics to the study of chromosome 21. AB - An extra copy of human chromosome 21 has been known for over twenty years to be the chromosomal abnormality in Down's syndrome; however, the biochemical and molecular basis governing expression of the phenotype is still poorly understood. Using the methods of somatic cell and molecular genetics, we have been studying genes and DNA sequences on chromosome 21 by constructing hamster/human hybrids containing a whole or partial chromosome 21 and assigning their locations on the chromosome. In particular, a family of repetitive sequences, some having only a few thousand copies in the human genome, have been used as cloned DNA markers to define deletions in these somatic cell hybrids. We have shown that this approach can significantly improve the resolution of fine chromosomal structures over the conventional cytogenetic analysis. The rationale behind this approach is the observation that a repetitive sequence probe often forms multiple bands after hybridizing to a Southern blot of digested hybrid DNA, and the band pattern appears to be unique for each human chromosome. Therefore, each band (sequence) can be assigned to a particular region of human chromosome 21 by comparing the band patterns from hybrids containing different portions of the chromosome. Results presented here showed that a 0.58-kb repetitive sequence probe can be used to identify deletions, translocations, and other more complicated rearrangements of chromosome 21 seen in patients with abnormalities of this chromosome. The advantage of using such a repetitive sequence probe over a unique sequence is that it can serve both as a repetitive sequence defining multiple sites (multiple bands on a Southern blot) in the genome and at the same time serve as a unique sequence defining a particular site (individual band). For the detection of deletions and other rearrangements, especially in small chromosomes such as 21, it is the former property that makes it very efficient in the initial assignment of a chromosome location. PMID- 2880546 TI - Technology transfer: lessons from experience--the communication process. PMID- 2880547 TI - Intravenous anesthesia and jet ventilation for laser microlaryngeal surgery. AB - Competition between otolaryngologists and anesthesiologists for the limited space of the airway results in compromised control for both concerns. The surgeon desires an unobstructed view, whereas the anesthesiologist must ensure adequate ventilation. The drawbacks of standard methods include inadequate airways, inadequate visualization, and operating room contamination from inspired gases. Since 1984, we have developed a technique utilizing jet ventilation delivered through a metal delivery system providing a relatively safe, ignition-free environment. A total intravenous anesthetic technique is used to avoid any environmental contamination. The newer short acting, high potency narcotic, sufentanil citrate, combined with a short acting muscle relaxant, atracurium besylate or vecuronium bromide, have made this technique an ideal one for our needs. The pulse oximeter provides an invaluable margin of safety. This technique has been employed in 36 microlaryngeal procedures performed on 21 patients with a uniformly smooth perioperative course and only one complication. The technique, possible pitfalls, and applications are discussed. PMID- 2880548 TI - [Phyto-ecological map of the larval breeding place of mosquitoes in mangrove swamps of Guadeloupe (supplementary note)]. PMID- 2880549 TI - [Digestive manifestations in a patient with type-IIB multiple endocrine neoplasms]. AB - The IIB or third type of multiple endocrine neoplasia is a very uncommon hereditary disease. It includes a digestive ganglioneuromatosis, a typical dysmorphia, a medullary thyroid cancer (MTC) sometimes a pheochromocytoma and seldom a hyperparathyroidism. We report a Men IIB case in a 19 years old patient who had been suffering from severe constipation and afflicted with a megacolon, known since early infancy. Diagnosis was documented by discovering a colonic ganglioneuromatosis and a MTC. A complete thyroidectomy was performed but cervical node metastasis were already present. The ganglioneuromatosis usually affects the whole alimentary tract, but megacolon although not regularly found occurs most frequently. Awareness of the diagnosis is easier when patients have big lips, eyelids, tongue (due to mucosal neuromas) and marfanoid habitus. The prognosis depends upon the MTC. It occurs early in the life, is often bilateral and has a trend to become uncontrollable in the young adult. The pheochromocytoma is often latent and affects only half of patients. The etiopathogeny of this disease still remains unknown. Family inquiry may help to an earlier diagnosis and therefore to a better prognosis. PMID- 2880550 TI - Effect of glutathione on alterations of liver DNA structure and metabolic activities induced in vivo by 2-acetylaminofluorene. AB - The effect on liver tissue of glutathione administration to rats treated for 7-14 days with 2-acetylaminofluorene was investigated. The DNA damage induced by the hepatotoxic agent and evaluated by the alkaline elution technique was significantly reduced by glutathione. Furthermore, GSH administration maintained liver GSH level, prevented the increase in alkaline phosphatase and reduced the decrease in glucose-6-phosphatase activity. GSH did not significantly influence the increase in gamma-glutamyl-transpeptidase and glutathione-S-transferase activities. PMID- 2880551 TI - Visual ecology of biting flies. AB - Many of the similarities in visual ecology between the Nematocera and Brachycera and within the Cyclorrhapha may reflect the evolution of blood-feeding in these groups. In Nematocera and Brachycera, blood-feeding is thought to have evolved from predatory or nectar-feeding behavior (138). Only females feed on hosts, and association with hosts generally occurs when hosts are close to the aquatic or semiaquatic habitats of the immatures. Flies feed on nectar, make appetitive flights, disperse, or migrate prior to blood-feeding, and then oviposit in water. Many species are nocturnal or crepuscular. In Cyclorrhapha, flies are closely associated with hosts. They may have arisen from compost-feeding flies that developed a larval dependence on vertebrate-produced microhabitats. Both sexes blood-feed, and mating occurs on or near hosts. Flies generally emerge in the proximity of hosts and maintain close contact with them. These species are diurnal, and their visual systems are well developed. Comparisons between closely related blood-feeding and non-blood-feeding species may provide insight into the visual ecology of blood-feeding species. Despite the different origins of hematophagy, there appears to be a convergence of morphology and behavior that is related to ecology rather than to phylogenetic relationships. This is clearly seen in host-location strategies by tsetse and tabanids. Even within groups such as mosquitoes, species that are active at the same time of day and in the same habitat have more in common than closely related species in different habitats. For this reason, an ecological review would be more cohesive than this phylogenetic discussion. However, because of the disproportionate amount of literature on a small number of groups, the phylogenetic approach is the most practical for this subject. However, this review does point out the great need for research on the less well-studied groups and behaviors. PMID- 2880552 TI - Physiology of osmoregulation in mosquitoes. PMID- 2880553 TI - Role of saliva in blood-feeding by arthropods. PMID- 2880554 TI - Advances in mosquito-borne arbovirus/vector research. PMID- 2880555 TI - Homeotic genes and the homeobox. PMID- 2880556 TI - Genetics of human cancer. AB - Study of hereditary cancer in humans has revealed new mechanisms in carcinogenesis. In particular, a new class of cancer gene, recessive in oncogenesis, accounts for dominantly transmitted predisposition to some cancers, and may play a primary role in the nonhereditary forms of most cancers. Comparison of polymorphic markers in lymphocytes and tumors has permitted the in vivo observation of somatic events that lead to genetic recombination. The tissue specificities of these recessive cancer genes suggest that their normal alleles, like those of oncogenes, play important roles in normal development. PMID- 2880557 TI - The conjugation system of F, the fertility factor of Escherichia coli. PMID- 2880558 TI - Pre-mRNA splicing. PMID- 2880559 TI - The evolution of multigene families: human haptoglobin genes. PMID- 2880561 TI - Properties of digitonin-solubilized calmodulin-dependent guanylate cyclase from the plasma membranes of Tetrahymena pyriformis NT-1 cells. AB - Calmodulin-dependent guanylate cyclase from Tetrahymena plasma membranes was solubilized in about a 22% yield by using digitonin in the presence of 0.2 mM CaCl2 and 20% glycerol. The detergent, when present in the assay at concentrations above 0.05%, diminished the basal and calmodulin-stimulated activity of the enzyme. Guanylate cyclase solubilized with digitonin was eluted from DEAE-cellulose with 200 mM KCl in a yield of 50%. Properties of the solubilized enzyme were similar to those of the native membrane-bound enzyme. The Kms for Mg-GTP and Mn-GTP were 140 and 30 microM, respectively. The enzyme required Mn2+ for maximum activity, the relative activity in the presence of Mg2+ being 30% of the activity with Mn2+. The solubilized enzyme retained the ability to be activated by calmodulin, with its extent being reduced as compared to the membrane-bound enzyme. The presence of a Ca2+-dependent calmodulin-binding site on the solubilized enzyme was shown by the Ca2+-dependent retention of the enzyme on a calmodulin-Sepharose-4B column. PMID- 2880560 TI - Modulation of acetyl-CoA carboxylase by inhibitors of IMP dehydrogenase: implications for insulin regulation. AB - The activity of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid biosynthesis, can be regulated by both adenine and guanine nucleotides in vitro. We have employed two inhibitors of IMP dehydrogenase, ribavarin and tiazofurin, to investigate a possible role for intracellular nucleotides in ACC regulation in rat adipocytes. Ribavarin, but not tiazofurin, leads to a profound time-dependent inhibition of ACC activity that is associated with a decrease in both intracellular ATP and GTP. This inactivating effect is largely reversed with guanosine, accompanied by increases in both ATP and GTP levels. Epinephrine mediated inactivation of ACC in intact cells is not altered by ribavarin incubation. However, in these experiments, insulin-mediated activation is observed only after ribavarin-induced inhibition of the enzyme. These data suggest that nucleotides may modulate ACC activity and influence is regulation by insulin in intact cells. The possible mechanisms underlying the insulin activation of ACC and the role of intracellular nucleotides in insulin action are discussed. PMID- 2880562 TI - Effect of a high-fat diet with partially hydrogenated fish oil on long-chain fatty acid metabolizing enzymes in subcellular fractions of rat liver. AB - Hepatic metabolism of long-chain fatty acids were studied in young male rats fed a semisynthetic diet containing 20% (w/w) partially hydrogenated fish oil (PHFO)2, with or without 2% (w/w) linoleic acid. The enzymic activities involved in the formation and breakdown of long-chain acyl-CoA were both increased in the animals fed the semisynthetic diet, compared to pellet-fed control animals. Thus, the specific palmitoyl-CoA synthetase activity increased slightly in both the mitochondrial (1.4-fold) and the microsomal (1.6-fold) fractions. In the peroxisome-enriched fraction the activity was increased (about 2.6-fold) only on addition of linoleic acid to the diet. The data are consistent with an increased catabolism of long-chain fatty acids by a peroxisomal and a mitochondrial pathway. Thus, the total carnitine palmitoyltransferase activity increased 2-fold in the mitochondrial fraction, and was partly prevented by added linoleic acid. Peroxisomal beta-oxidation activity was also increased (about 7-fold) in livers of PHFO-fed rats, but did not change when linoleic acid was added. The PHFO-fed rats also revealed elevated capacity for hydrolysis of palmitoyl-CoA in both the mitochondrial (2.4-fold) and the cytosolic (2.0-fold) fractions and the latter was almost completely and selectively prevented by added linoleic acid. The s values of mitochondria and peroxisomes varied with the dietary regime, and some of the observed changes in the specific activities of the fatty acid metabolizing enzymes with multiple subcellular localization can be explained as an effect of changes in the s values of the organelles. Thus, the s value of mitochondria increased 1.8-fold as a result of PHFO feeding, but was fully prevented by linoleic acid in the diet. On the other hand, the s values of peroxisomes decreased by about 50% on feeding a PHFO diet, and by about 25% with added linoleic acid. PMID- 2880563 TI - A hexameric form of the Neurospora crassa plasma membrane H+-ATPase. AB - As isolated by our recently developed large-scale procedure, the Neurospora plasma membrane H+-ATPase exists as a homogeneous, oligomeric complex of 105,000 Da monomers with a molecular mass equivalent to a spherical protein of about 1 million Da, as judged by its behavior during chromatography on calibrated columns of Sepharose CL-6B and CL-4B. Treatment of this complex with the nonionic detergent, Tween 20, followed by Sepharose column chromatography in the presence of this detergent produces particles with an apparent molecular mass reduced by 100-300 kDa, and, importantly, when the isolated complex is treated with Tween 20 and then subjected to Sepharose chromatography in the absence of detergent, fully viable, largely detergent-free, homogeneous particles with a molecular mass equivalent to a spherical protein of 670,000 Da are formed. As assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, treatment of the particles isolated in the presence of Tween 20 with glutaraldehyde progressively yields dimers, trimers, tetramers, pentamers, and hexamers of the 105,000-Da monomer, with the expected precursor-product relationships, but no species larger than a hexamer is formed. These results thus strongly indicate that these particles are hexamers of 105,000-Da monomers. Glutaraldehyde crosslinking experiments with the ca. 1 million- and 670,000-Da particles indicate that they too are hexamers, suggesting that the differences in the apparent sizes of the three types of particles are most likely due to bound detergents. Possible implications of these findings are discussed. PMID- 2880565 TI - Inhibition of the proton pumping ATPases of yeast and oat root plasma membranes by dicyclohexylcarbodiimide. AB - The inhibition of the proton-pumping ATPases of yeast and oat root plasma membranes by dicyclohexylcarbodiimide (DCCD) can be correlated with the covalent incorporation of the inhibitor. Full inhibition of the yeast enzyme required the incorporation of about 1 mol DCCD/mol of the ATPase polypeptide of 100 kDa. A kinetic study of the interaction of DCCD with the yeast and oat ATPases indicates a second-order rate constant of about 500 M-1 min-1 and a stoichiometry of 1 mol DCCD/mol of enzyme, in agreement with the amount of DCCD incorporated by the yeast enzyme. It is proposed that DCCD reacts with a single carboxylic group present in a hydrophobic region of these proton-pumping ATPases and which could participate in proton binding and transport. PMID- 2880564 TI - Interaction among substrates, inhibitors and Mn2+ bound to glutamine synthetase as studied by NMR relaxation rate measurements. AB - The interaction of Mn2+ with the substrate glutamate and several transition state analog inhibitors of glutamine synthetase has been studied. With Mn2+ bound to the tight binding site, the frequency and temperature dependence of the paramagnetic contribution to solvent water proton relaxation rates demonstrate changes in the structure of the metal ion environment induced by substrate or inhibitor binding. The water proton relaxation rate data also show differences in the metal ion environment in the presence of glutamate compared to methionine sulfoximine, a structural analog of an intermediate in the reaction mechanism. Additionally, the distance between the metal ion and the phosphorus atom of an inhibitor, 2-amino-4-phosphonobutyric acid, was estimated (approximately 5 A) using NMR measurements. These data are in accord with our recent hypothesis that the role of the metal ion is to stabilize the tetrahedral adduct formed on the reaction pathway. PMID- 2880566 TI - Inactivation of enzymes and oxidative modification of proteins by stimulated neutrophils. AB - Differentiated, stimulated HL-60 cells and freshly isolated, stimulated neutrophils inactivate glutamine synthetase (L-glutamate:ammonia ligase (ADP forming), EC 6.3.1.2) either inside or outside of Escherichia coli. Stimulated neutrophils also inactivate at least four endogenous enzymes which are inactivated by mixed-function oxidation (MFO) systems in vitro (L. Fucci, C.N. Oliver, M.J. Coon, and E.R. Stadtman (1983) Proc. Natl. Acad. Sci. USA 80, 1521 1525). The inactivation of glutamine synthetase by stimulated neutrophils exhibits characteristics similar to those previously described using both enzymic and nonenzymic MFO systems (R.L. Levine, C.N. Oliver, R.M. Fulks, and E.R. Stadtman (1981) Proc. Natl. Acad. Sci. USA 78, 2120-2124). Although the reaction occurs in the absence of Fe(III), it is stimulated by added Fe (III). Inactivation required molecular oxygen and is partially inhibited by Mn(II), catalase, superoxide dismutase, and metal chelators, ethylenediaminetetraacetic acid and o-phenanthroline. Both the kinetics and the extent of glutamine synthetase inactivation differ when neutrophils are stimulated with phorbol esters compared with formylated peptides. Glutamine synthetase inactivation catalyzed by MFO systems is accompanied by the formation of protein carbonyl derivatives which form stable hydrazones when treated with 2,4 dinitrophenylhydrazine. Multiple carbonyl derivatives are formed in the soluble protein fraction of stimulated neutrophils and these derivatives collectively exhibit an absorbance spectrum similar to that of glutamine synthetase inactivated by liver microsomal cytochrome P-450 MFO system (K. Nakamura, C.N. Oliver, and E.R. Stadtman (1985) Arch. Biochem. Biophys. 240, 319-329). PMID- 2880568 TI - [Pharmacotherapy of essential hypertension]. PMID- 2880567 TI - On the interaction between anthralin and mitochondria: a revision. AB - Anthralin is an inhibitor of oxidative phosphorylation at concentrations found in vivo. ADP-stimulated oxygen consumption is diminished. Consequently, the rate of ATP synthesis is reduced and mitochondrial ATP content declines. Neither the isolated ATPase (F1F0-ATPase), nor the mitochondrial membrane-bound ATPase are influenced by the drug. Respiration under resting conditions is not affected. The experimental data unequivocally indicate that anthralin is not an uncoupler of oxidative phosphorylation, as previously stated. Furthermore, the interpretation that respiratory deficiency induced in yeast strains by anthralin is a consequence of petite mutations has to be reconsidered. Under in vivo conditions, anthralin inhibits respiration per se. Our experiments, including the electron spin resonance spectroscopy, reveal that anthralin alters mitochondrial membrane structure and function simultaneously. A redox or free-radical mediated step may be involved. In consequence, inhibition of ATP production occurs which may become the limiting factor for increased cellular metabolism in psoriasis. PMID- 2880569 TI - [Antihypertensive therapy in pregnancy]. PMID- 2880570 TI - [Round table: Current aspects of drug therapy in pregnancy and labor exemplified by tocolysis at the clinic and in general practice]. PMID- 2880571 TI - Surgical treatment of Takayasu's disease. AB - Thirty-nine patients (mean age: 33 years) with Takayasu's disease were observed over the past 8 years. Among these patients, 33 had surgical intervention with a mean follow-up of 4 years. Lesions of the aortic arch were the most common (29 patients, 69 lesions) and frequently were associated with lesions in another site as well. However, in this group of patients, the infrequent presence of signs of cerebral vascular insufficiency limited the number of suitable surgical candidates to 14 patients. Lesions of the renal arteries were noted in 25 patients (37 lesions) and were associated with coarctation of the thoracoabdominal aorta in 12 patients. In contrast to lesions of the aortic arch, the presence of severe hypertension was a frequent indication for surgery in Takayasu's disease. Twenty-one patients had operation. Twenty of 21 patients were considered cured or improved of hypertension. The one patient who received no benefit was the only operative death of the study. In conclusion, although Takayasu's disease is progressive and the life expectancy is foreshortened, hypertension secondary to aortic and renal artery lesions is a frequent and important indication for aggressive operative treatment. PMID- 2880572 TI - [Aortic insufficiency in certain so-called systemic diseases]. AB - The authors present a retrospective study of all the patient followed up for systemic disease in the rheumatology Department of Bichat hospital between 1975 and 1984 in whom aortic regurgitation developed. Only rare or previously undescribed associations were retained: two MacDuffie syndromes, one adult form of Still's disease, one Takayashu's disease, one association of rheumatoid arthritis and Takayashu's disease, one rheumatoid arthritis, one Cogan's syndrome and two cases of disseminated lupus erythematosis. The authors use these cases and a review of the literature to discuss the possible physiopathological mechanisms of the aortic regurgitation. This study confirms the value of regular clinical cardiovascular examination with echocardiography in cases with progressive symptoms. The evolution of the vascular disease seems to be more or less parallel to that of the systemic disease and in a significant number of cases it becomes sufficiently severe to become the main clinical problem. In our series, there was one sudden death, one death due to cardiogenic pulmonary oedema and three patients required aortic valve replacement. PMID- 2880573 TI - Temperature and oxygen regulated expression of a glutamine synthetase gene from Vibrio alginolyticus cloned in Escherichia coli. AB - Glutamine synthetase (GS) synthesis in Vibrio alginolyticus was regulated by temperature, oxygen and nitrogen levels. A GS gene, glnA from V. alginolyticus was cloned on a 5.67 kb insert in the recombinant plasmid pRM210, which enabled Escherichia coli glnA, ntrB, ntrC deletion mutants to utilize (NH4)2SO4 as a sole source of nitrogen. The V. alginolyticus glnA gene was expressed from a regulatory region contained within the cloned fragment. V. alginolyticus glnA expression from pRM210 was subject to regulation by temperature, oxygen and nitrogen levels. GS specific activity in an E. coli wild-type strain was not affected by temperature or oxygen. pRM211 was a deletion derivative of pRM210 and GS production by pRM211 was not regulated by temperature, oxygen or nitrogen levels in E. coli. PMID- 2880575 TI - Interaction of calcium antagonists with beta-adrenoceptor blocking agents. AB - Responsiveness to verapamil, the best studied calcium antagonist, was examined in cardiac preparations of rabbits pretreated with beta-adrenoceptor blockers (propranolol 2 mg/kg or oxprenolol 4 mg/kg s.c.) twice daily for either one or six weeks. Using this dose-regimen, the degree of cardiac beta-adrenoceptor blockade in conscious rabbits was substantial and similar for propranolol and oxprenolol. When administered for one week, neither propranolol nor oxprenolol affected to any marked extent the electrical and mechanical response to verapamil, diltiazem or fendiline in tissues isolated from various parts of the heart. In contrast, pretreatment with propranolol for six weeks resulted in a significant aggravation of the negative inotropic effect of verapamil in both atrial and ventricular muscle, and the verapamil-induced delay in atrio ventricular and intra-ventricular conduction also became more pronounced. The same long-term administration of oxprenolol, one of the beta-blockers with "intrinsic" sympathomimetic activity, did not alter the atrial or ventricular contractile response to verapamil and did not significantly increase the lengthening of atrio-ventricular conduction time occurring in the presence of verapamil. It is concluded that from the point of view of adverse direct cardiac interactions with verapamil prolonged administration of oxprenolol appears to be less dangerous than chronic treatment with propranolol. It is also assumed that in those cases in which acute administration of verapamil may be necessary, concomitant chronic blockade of cardiac beta-adrenoceptors is less dangerous if drugs known to possess not only beta-adrenoceptor blocking properties, but also some "intrinsic" sympathomimetic activity are applied. PMID- 2880574 TI - Relationship between nitrogen assimilation and cephalosporin synthesis in Streptomyces clavuligerus. AB - The levels of three enzymes of the beta-lactam antibiotic pathway and overall cephalosporin production were subject to nitrogen source repression in Streptomyces clavuligerus. The specific activities of isopenicillin N synthetase ("cyclase") and deacetoxycephalosporin C synthetase ("expandase") measured during the exponential phase depended on the nitrogen source employed, following a pattern that roughly correlated with the corresponding antibiotic production. The effects on isopenicillin N epimerase ("epimerase") activities were less marked than those on the cyclase and expandase. Production of cephalosporins and enzymatic activities were not related to the growth rate of the cultures. Glutamate, glutamine and alanine inhibited production when added to resting cell systems, while lysine and alpha-aminoadipate were stimulatory. No clear relationship could be drawn between cephalosporin production or beta-lactam synthetase activities and the activities of enzymes of ammonium assimilation (glutamine synthetase, glutamate synthase and alanine dehydrogenase). The intracellular pools of free glutamine, alanine and ammonium were the only ones markedly affected by the nitrogen source in the wild type and mutants, but these amino acids did not seem to play an obvious role as intracellular mediators of nitrogen control. PMID- 2880576 TI - Genome variation among varicella-zoster virus isolates derived from different individuals and from the same individuals. AB - We have used 12 restriction enzymes to analyse the DNA of 24 clinical isolates of VZV derived from 12 patients in order to compare isolates derived from different individuals and derived serially from the same individual. As reported previously, only a small proportion of the isolates differed with respect to the presence or absence of restriction sites. However, we found that the size of DNA fragments generated from all the isolates derived from different patients varied in any of four regions, one of which was first recognized in this study. In one case, where multiple isolates recovered from the same individual were analysed, each was distinguished from the others not only by differences in the variable regions but also by the presence or absence of a restriction site in a nonvariable region. This suggests that multiple strains of VZV can be present in the same human host. PMID- 2880577 TI - Immunogenicity of an Escherichia coli multivalent pilus vaccine in chickens. AB - Immunogenicity of an oil-emulsified Escherichia coli multivalent pilus vaccine was evaluated in 4-week-old chickens. The vaccine contained 180 micrograms of pilus protein from each of serotypes O1 and O78 and 170 micrograms of pilus protein from serotype O2. Chickens were vaccinated twice subcutaneously at 4 and 6 weeks old and challenged via the posterior thoracic air sac with E. coli serotype O1, O2, or O78 2 weeks after the last vaccination. Unvaccinated challenged chickens suffered 8% to 26% mortality; no vaccinated chickens died. Vaccinated chickens had very mild gross lesions in the air sacs, livers, and pericardial sacs and eliminated E. coli more efficiently than the unvaccinated challenged chickens. The results showed that a multivalent pilus vaccine protects chickens against active respiratory infection. PMID- 2880578 TI - Biological and immunological characterization of pili of Escherichia coli serotypes O1, O2, and O78 pathogenic to poultry. AB - Pili of Escherichia coli serotypes O1, O2, and O78 pathogenic to poultry were isolated and purified by sucrose-density-gradient centrifugation. Each serotype expressed only one type of pilus. The pili of the three serotypes had similar densities and were morphologically similar by electron microscopy. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, however, showed that they were slightly different in subunit molecular mass. Slide agglutination, immunodiffusion, and immunoblot tests were used to test for antigenic relationships between these pili and reference pili. Pili of serotype O78 were type 1, but pili of serotypes O1 and O2 were not, as once believed. However, pili of serotype O2 reacted positively with anti-type 1 serum in immunoblot assay, suggesting the presence of some common antigenic epitopes among these pili. PMID- 2880579 TI - Neural control of gene expression in skeletal muscle. Calcium-sequestering proteins in developing and chronically stimulated rabbit skeletal muscles. AB - Tissue contents of the sarcoplasmic-reticulum Ca2+-ATPase (Ca2+ +Mg2+-dependent ATPase), of calsequestrin and of parvalbumin were immunochemically quantified in homogenates of fast- and slow-twitch muscles of embryonic, maturing and adult rabbits. Unlike parvalbumin, Ca2+-ATPase and calsequestrin were expressed in embryonic muscles. Presumptive fast-twitch muscles displayed higher contents of these two proteins than did presumptive slow-twitch muscles. Calsequestrin steeply increased before birth and reached adult values in the two muscle types 4 days after birth. The main increase in Ca2+-ATPase occurred during the first 2 weeks after birth. Denervation of postnatal fast- and slow-twitch muscles decreased calsequestrin to amounts typical of embryonic muscle and suppressed further increases of Ca2+-ATPase. Denervation caused slight decreases in Ca2+ ATPase in adult fast-twitch, but not in slow-twitch, muscles, whereas calsequestrin was greatly decreased in both. Chronic low-frequency stimulation induced a rapid decrease in parvalbumin in fast-twitch muscle, which was preceded by a drastic decrease in the amount of its polyadenylated RNA translatable in vitro. Tissue amounts of Ca2+-ATPase and calsequestrin were essentially unaltered up to periods of 52 days stimulation. These results indicate that in fast- and slow-twitch muscles different basal amounts of Ca2+-ATPase and calsequestrin are expressed independent of innervation, but that neuromuscular activity has a modulatory effect. Conversely, the expression of parvalbumin is greatly enhanced by phasic, and drastically decreased by tonic, motor-neuron activity. PMID- 2880580 TI - Regulation of early enzymes of ergosterol biosynthesis in Saccharomyces cerevisiae. AB - In order to determine the regulation mechanisms of ergosterol biosynthesis in yeast, we developed growth conditions leading to high or limiting ergosterol levels in wild type and sterol-auxotrophic mutant strains. An excess of sterol is obtained in anaerobic sterol-supplemented cultures of mutant and wild type strains. A low sterol level is obtained in aerobic growth conditions in mutant strains cultured with optimal sterol supplementation and in wild type strain deprived of pantothenic acid, as well as in anaerobic cultures without sterol supplementation. Measurements of the specific activities of acetoacetyl-CoA thiolase, HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) synthase and HMG-CoA reductase (the first three enzymes of the pathway), show that in cells deprived of ergosterol, acetoacetyl-CoA thiolase and HMG-CoA synthase are generally increased. In an excess of ergosterol, in anaerobiosis, the same enzymes are strongly decreased. A 5-10-fold decrease is observed for acetoacetyl-CoA thiolase and HMG-CoA synthase. In contrast, HMG-CoA reductase is only slightly affected by these conditions. These results show that ergosterol could regulate its own synthesis, at least partially, by repression of the first two enzymes of the pathway. Our results also show that exogenous sterols, even if strongly incorporated by auxotrophic mutant cells, cannot suppress enzyme activities in aerobic growth conditions. Measurement of specific enzyme activities in mutant cells also revealed that farnesyl pyrophosphate thwarts the enhancement of the activities of the two first enzymes. PMID- 2880581 TI - Changes in the plasma membrane ATPase activity in relationship to cell proliferation in Dictyostelium. AB - The plasma membrane ATPase activity of Dictyostelium amoebae increases ca 2.5 fold from non dividing stationary phase cells to synchronously growing cells. This increase in ATPase activity takes place during the three hours lag period that precede the cell division after diluting stationary cells into fresh medium and is prevented by cycloheximide. No differences in the Km for ATP or in the optimal pH for activity were observed in kinetic studies carried out with purified plasma membranes from stationary and proliferating cells. PMID- 2880582 TI - Biosynthesis of porcine kidney D-amino acid oxidase. AB - The biosynthesis of a porcine kidney peroxisomal enzyme, D-amino acid oxidase (EC 1.4.3.3., DAO), was investigated. Pig kidney mRNA as well as free and membrane bound polysomes were used to investigate in vitro protein synthesis using a rabbit reticulocyte lysate. mRNA and free polysomes, but not membrane-bound polysomes, directed the synthesis of DAO. To examine the in vivo synthesis of the enzyme, a pig kidney cell line (LLC-PK1) was biosynthetically labelled. Both the in vitro and in vivo synthesized DAO had the same molecular weight, 38,000, as that of the purified enzyme. These results indicate strongly that DAO is synthesized on free ribosomes and transferred to the interior of peroxisomes without any proteolytic modification. PMID- 2880583 TI - The mdr1 gene, responsible for multidrug-resistance, codes for P-glycoprotein. AB - The development of simultaneous resistance to multiple drugs in cultured cells occurs after selection for resistance to single agents. This multidrug-resistance phenotype is thought to mimic multidrug-resistance in human tumors treated with chemotherapy. Both the expression of a membrane protein, termed P170 or P glycoprotein, and the expression of a cloned DNA fragment, termed mdr1, have been shown independently to be associated with multidrug-resistance in cultured cells. In this work, we show that human KB carcinoma cells which express the mdr1 gene also express P-glycoprotein, and that cDNAs encoding P-glycoprotein cross hybridize with mdr1 cDNAs. Thus, the mdr1 gene codes for P-glycoprotein. PMID- 2880584 TI - Stimulation by a tumor-promoting phorbol ester of acetyl-CoA carboxylase activity in isolated rat hepatocytes. AB - Acetyl-CoA carboxylase (EC 6.4.1.2) in hepatocytes from meal-fed rats was activated by phorbol myristate acetate (PMA) in a time- and concentration dependent fashion. This activation can account for the PMA-induced stimulation of de novo fatty acid synthesis. Purified rat-liver acetyl-CoA carboxylase was found to be phosphorylated and activated by protein kinase C, thus providing a possible mechanism for the metabolic action of PMA in intact hepatocytes. PMID- 2880585 TI - A fluorescent derivative of the oligomycin-sensitivity conferring protein (acrylodan-OSCP). Evidence for polarity changes in the environment of CYS118 of OSCP upon binding to mitochondrial F1. AB - The fluorescent probe, 6-acryloyl-2-dimethylaminonaphtalene (acrylodan) was reacted with the oligomycin-sensitivity conferring protein (OSCP). Acrylodan bound covalently to the single cysteinyl residue of the protein. Acrylodan-OSCP was fully competent in conferring oligomycin sensitivity to the mitochondrial F0 F1 ATPase complex. The fluorescence emission peak of acrylodan-OSCP was blue shifted compared to that of an acrylodan-mercaptoethanol adduct, which means that acrylodan experiences a hydrophobic environment in OSCP. Binding of acrylodan OSCP to the isolated F1 was accompanied by a red shift of fluorescence. It was achieved in less than 1 s at 25 degrees C. The titration curve revealed one high affinity OSCP binding site per F1. Acrylodan-OSCP appears to be an interesting tool for studying the dynamics of structural changes within the mitochondrial ATPase complex. PMID- 2880586 TI - Inhibition of alpha 1-adrenergic responsiveness in intact cells by a new, irreversible receptor antagonist. AB - A novel alpha 1-adrenoreceptor antagonist, 1-(4-amino-6,7-dimethoxy-2 quinazolinyl)-4-(2-bicyclo [2.2.2] octa-2,5-dienylcarbonyl) piperazine, was synthesized and shown to potently block alpha 1-adrenoceptor-induced Ca2+ mobilization in intact rat parotid acinar cells. Irreversible inhibition was complete in less than 5 min. This alkylating prazosin derivative blocked Ca2+ release (IC50 approximately 5 X 10(-10)M) and [3H]-prazosin membrane binding (IC50 approximately 3 X 10(-10)M) in a concentration dependent fashion and increased the EC50 of epinephrine for Ca2+ efflux by approximately 35 fold. The agent however had no effect on muscarinic receptor-induced Ca2+ mobilization, or beta-adrenoreceptor-induced protein secretion, from cells. These findings suggest that this irreversible alpha 1-adrenoreceptor antagonist will be a valuable tool in probing alpha 1-adrenoreceptor function and metabolism in intact cells. PMID- 2880587 TI - Independent bindings of Mn2+ and Mg2+ to the active site of B. cereus glutamine synthetase. AB - Glutamine synthetase purified from Bacillus cereus IFO 3131 was modified by iodoacetamide and the ATP analog 5'-p-fluorosulfonylbenzoyladenosine (FSBA). Only Mg2+-dependent activity was inactivated by iodoacetamide, whereas only Mn2+ dependent activity was inactivated by FSBA. When iodoacetamide-treated enzyme was reacted with FSBA, Mn2+-dependent activity was also inactivated. Mg2+ plus Mn2+ dependent activity was inactivated in any case. The results suggested that the binding sites of Mn2+ and Mg2+ are separate from each other in the active site of B. cereus glutamine synthetase and that bindings of Mg2+ and Mn2+ to each site are required for normal activity in vivo. PMID- 2880588 TI - Solubilization of novel binding sites for [3H]glutamate in rat adrenal. AB - [3H]Glutamate binding sites were solubilized from the rat adrenal glands by treatment of the membranous homogenate preparations with various detergents. The binding in solubilized preparations was dependent on the incubation temperature and incubation time, and reached an equilibrium within 40 min of incubation at 30 degrees C. Scatchard analysis revealed that the binding sites consisted of a single component with a Kd of 0.15 microM and a Bmax of 35.9 pmoles/mg protein, respectively. The binding was significantly displaced by L-isomers of the structure-related compounds, but not by D-isomers. Quisqualic acid exhibited a concentration-dependent inhibition of the binding, whereas neither N-methyl-D aspartic acid nor kainic acid elicited such a prominent diminution. These results suggest that the rat adrenal indeed contains novel binding sites for the central neurotransmitter candidate. PMID- 2880589 TI - Neuronal/lymphoid membrane glycoprotein MRC OX-2 is a member of the immunoglobulin superfamily with a light-chain-like structure. AB - The MRC OX-2 antigen is a membrane glycoprotein of about 45,000 Mr present on rat neurons, thymocytes, B cells, follicular dendritic cells, endothelium and smooth muscle. Sequence of cDNA clones indicates it is a member of the Ig superfamily containing 248 amino acids organized like an Ig light chain with a V-like domain and a C-like domain followed by a transmembrane and cytoplasmic sections. There is a sequence with homologies with J-regions but analysis of the gene for human OX-2 shows that this is part of the V-domain exon and there is not a separate J region exon as in the T cell receptor or Ig chains. The relationship of OX-2 to the other Ig-related neuronal/thymocyte antigen Thy-1 and the evolution of the Ig superfamily are discussed. PMID- 2880590 TI - Effect of dexamethasone on cytochrome P-450 mediated metabolism of 2 acetylaminofluorene in cultured rat hepatocytes. AB - The metabolism of 2-acetylaminofluorene (AAF) to its six oxidative metabolites has been used to investigate the effect of dexamethasone on cytochrome P-450 activity in cultured rat hepatocytes. In control hepatocytes the metabolism of AAF to its 1-, 5-, 7-, 9- and N-hydroxylated metabolites rapidly declined in culture over the first 24 hr while 3-hydroxylation remained relatively constant. These activities either remained unchanged or increased slightly during the next 48 hr in culture. The addition of dexamethasone (100 nM) to the culture medium had little effect in arresting the initial decline but by 72 hr the 7-, 5- and 3 hydroxylations increased to values 2.5, 16 and 21 times the respective 24-hr values. The inductive effect of dexamethasone on the 3- and 5-hydroxylations of AAF was maximal at 100 nM whereas the 7-hydroxylation increased linearly as a function of the dexamethasone concentration up to 1 microM. Cortisol and corticosterone and the non-glucocorticoids fluoxymesterone and methyltestosterone induced a pattern of AAF metabolism resembling that in dexamethasone-treated cultures, suggesting that a range of steroids not restricted to glucocorticoids may induce multiple cytochrome P-450 isozymes via related mechanisms. Pregnenolone 16 alpha-carbonitrile induced only the 7-hydroxylation of AAF probably reflecting induction of cytochrome P-450p. While dexamethasone was a strong inducer of the 3- and 5-hydroxylations of AAF in hepatocyte culture, assay of these activities in freshly isolated cells after in vivo treatment with dexamethasone showed a strong induction of 7-hydroxylation but only small effects on 3- and 5-hydroxylations. Indeed the profile of AAF metabolism induced in culture by dexamethasone resembles more closely the profile induced by 3 methylcholanthrene in vivo. These data suggest that factors yet to be identified strongly influence the steroid-induced pattern of cytochrome P-450 gene expression. PMID- 2880591 TI - Two beta-adrenergic pharmacophores on the same molecule. A set of agonist antagonist combinations. AB - A series of compounds containing combinations of one or two pharmacophores of the agonist type (isoproterenol) or the antagonist type (propranolol or alprenolol) on the same molecule were prepared. The pharmacophores were connected by a derivative of polyethylene glycol with an average length of six atoms (carbon and oxygen). Furthermore, compounds containing two alprenolol residues, separated by chains of average lengths of 70 or 145 atoms, were synthesized. The abilities of these compounds to interact with beta-adrenoceptors of rat heart and lung tissues were examined by measuring the following parameters: competitive binding with [3H]dihydroalprenolol, activation of adenylate cyclase, and inhibition of isoproterenol-stimulated adenylate cyclase. The affinity of the compound with two isoproterenol pharmacophores for receptor was about the same as that with one isoproterenol pharmacophore and between 30 and 200 times weaker than that of (+/ )isoproterenol. Both mono- and bis-pharmacophore compounds partially stimulated catecholamine sensitive adenylate cyclase and at high concentrations inhibited the stimulation produced by (-)isoproterenol. The affinity of the compound with antagonist (propranolol) and agonist (isoproterenol) pharmacophores on the same molecule was intermediate between that of propranolol and isoproterenol. The compound was only able to inhibit adenylate cyclase activity. Compounds containing two antagonist (alprenolol) pharmacophores bound to receptors with affinities from an order of magnitude lower to about equal to that of the compound containing one pharmacophore. When membranes were preincubated with compounds containing two antagonist pharmacophores and then washed extensively, there were persistent effects of all of these compounds on the binding constants of [3H]dihydroalprenolol. All of these compounds were only able to inhibit adenylate cyclase activity and none exhibited any subtype selectivity at beta adrenoceptors. The results suggest that, in the beta-adrenergic system, compounds with agonist and antagonist substituents on the same molecule exhibit properties of the substituent with the higher affinity for beta-adrenoceptor, and no agonist activity is evident when two antagonist pharmacophores are linked on the same molecule. All of the above results may be explained without recourse to cross linking of beta-adrenoceptors with two pharmacophores, a phenomenon cited in similar studies of receptors for opiates and gonadotropin-releasing hormone. PMID- 2880592 TI - Effects of thiazinamium chloride and other antihistamines on phosphatidylcholine secretion in rat type II pneumocyte cultures. AB - Thiazinamium chloride (TCl) stimulated phosphatidylcholine secretion in cultures of adult rat type II pneumocytes in a concentration-dependent manner in the range 10(-9)-10(-6) M. At the optimal concentration, secretion was stimulated by 46% which is approximately half the stimulatory effect of the beta-agonists terbutaline and isoproterenol. TCl did not increase the rate of choline incorporation into cellular phosphatidylcholine or of lactate dehydrogenase release so its effect on secretion was not secondary to phosphatidylcholine synthesis or cell injury. Since TCl has antihistaminic properties, we examined the effects of other antihistamines. The H-1 antagonists promethazine, which is structurally similar to thiazinamium, and pyrilamine, which has a different structure, also stimulated secretion but the H-2 antagonist, cimetidine, did not. The effects of TCl and pyrilamine were additive to those of terbutaline, suggesting that the mechanisms of action of the antihistamines and the beta agonist were different. Although we were unable to demonstrate an inhibitory effect of histamine itself on either basal or terbutaline-stimulated phosphatidylcholine secretion, it is possible that histamine plays a regulatory role in lung surfactant secretion. PMID- 2880593 TI - Concomitant induction of cytosolic but not microsomal epoxide hydrolase with peroxisomal beta-oxidation by various hypolipidemic compounds. AB - The effects of two cholesterol-lowering (probucol and 1-benzyl-imidazole), three triglyceride- and cholesterol-lowering (clofibrate, tiadenol and fenofibrate) and one triglyceride-lowering (acetylsalicylic acid) compounds on the specific activities of two lipid-metabolizing enzymes (cyanide-insensitive peroxisomal beta-oxidation and palmitoyl-CoA hydrolase) and two xenobiotic metabolizing enzymes (cytosolic (cEH) and microsomal epoxide hydrolase (mEHb] from the livers of male Fischer F-344 rats were investigated. With the exception of probucol and acetylsalicylic acid, all compounds tested caused a dose-dependent hepatomegaly. Taken on a weight basis fenofibrate was the most effective inducer, causing a 20 fold induction of peroxisomal beta-oxidation, a 13-fold induction of cEH activity and a 16-fold induction of palmitoyl-CoA hydrolase activity. The other compounds with triglyceride-lowering activity also induced cEH as well as peroxisomal beta oxidation and palmitoyl-CoA hydrolase activity. The potency of each individual drug was similar for induction of cEH activity as compared with that of peroxisomal beta-oxidation and palmitoyl-CoA hydrolase activity, but very dissimilar for mEHb, which upon treatment with any of the triglyceride-lowering compounds was either not or only minimally (less than 1.5-fold) induced. 1 Benzylimidazole possessing exclusively cholesterol-lowering activity increased mEHb much more than either cEH or peroxisomal beta-oxidation. The absence of an enhancement of cEH activity in in vitro studies confirmed that the increase in enzyme activity by the test compounds is not caused by activation. cEH activity was also induced in the kidney but only about 2-fold by fenofibrate, tiadenol and acetylsalicylic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2880594 TI - Cardiovascular effect of sparteine in anaesthetized dogs with and without blockade of cardiac autonomic nerves. AB - L-Sparteine sulfate (sparteine, 3 mg/kg) was injected intravenously over 3 min in 12 anaesthetized dogs in order to evaluate the inotropic effect of this antiarrhythmic drug on the heart in intact organisms. There was a discrete decline in left ventricular dP/dtmax which was transient within 9 min. No influence could be detected on right ventricular pressure rise velocity. Aortic pressure increased by about 15% and a parallel increase in left ventricular enddiastolic pressure was observed. Heart rate was slightly diminished. Pharmacological blockade of cardiac autonomic nerves did not influence considerably the effect of sparteine. Pretreatment with captopril and phentolamine did not abolish the vasoconstrictive property which was also present in a reserpine pretreated dog. Sparteine shows no pronounced inotropic effect in the heart in situ. It increases arterial blood pressure by direct vascular constriction. PMID- 2880595 TI - [Synthesis and H2-antagonistic action of N,N-substituted 1,3,4-oxadiazole-2,5 diamine. 30. H2-antihistaminics]. AB - The semicarbazides 1 and 5a-c were transformed in high yields into the biureas 3a, b and the thiobiureas 10a-c and 11a-c by addition to appropriate iso(thio)cyanates and subsequently cyclisized to the N,N'-substituted 1,3,4 oxadiazole-2,5-diamines by means of elimination of water or hydrogen sulphide. The synthesized compounds were tested for H2-antagonistic activity at the isolated spontaneously beating guinea-pig atrium, where especially 4a, b and 12c showed pronounced H2-antagonistic action. PMID- 2880596 TI - [The action of various doses of the new imidazole H2-receptor antagonist etintidine on intragastric acidity in man]. AB - The chemical structure of etintidine differs from that of cimetidine by the addition of an ethinyl group to the terminal methyl group of the side chain. We investigated the influence of etintidine 300 or 400 mg b.d. and of etintidine 300 or 600 mg nocte, cimetidine 800 mg nocte versus placebo in two different double blind randomized cross-over studies on 24-h intragastric acidity and nocturnal volume and acid secretion (12:00 midnight to 6:00 a.m.) in 12 and 8 healthy male volunteers, respectively. 5-10 ml of gastric contents were aspirated hourly via a nasogastric tube. The pH of the samples was determined using a glass electrode. The results were expressed in terms of H+-activity (mmol/l). Etintidine 300 or 400 mg b.d. reduced day- and nighttime acidity by 53 and 60% or 41 and 41%, respectively. Nocturnal acid secretion (mmol/l) was inhibited by 38 and 42%, resp. Etintidine 300 or 600 mg nocte and cimetidine 800 mg nocte (9:00 p.m.) lowered nocturnal intragastric acidity by 69, 84 and 79%, resp. Daytime inhibition was not observed. Our results suggest, that 1. etintidine 300 and 400 mg b.d. are equipotent in promoting peptic ulcer healing and 2. that this new imidazole H2-receptor antagonist is also effective in a single bedtime dose. PMID- 2880597 TI - Serum apolipoprotein A-II as a marker of change in alcohol intake in male drinkers. AB - The relative usefulness of high-density lipoprotein cholesterol (HDL-C) and the HDL components, apolipoproteins A-I and A-II (Apo A-I and Apo A-II), as prospective markers of change in alcohol intake was compared to gamma-glutamyl transferase (gamma GT) and erythrocyte mean corpuscular volume (MCV) in a controlled crossover trial of 46 moderate male drinkers whose alcohol intake was reduced by approximately 80% for six weeks by the substitution of their normal drinking habits for a low alcohol content beer only. Only serum Apo A-II levels correlated significantly with self-reported alcohol intake at the commencement of the study (r = 0.46; P less than 0.001). All five indices fell significantly with reduction of alcohol intake. The change in these indices between normal and low alcohol intake periods correlated directly with change in alcohol intake, the highest correlation being with delta Apo A-II (r = 0.72; P less than 0.001). Using discriminant analysis this variable was found to achieve an accuracy of 96% in classifying subjects into the correct drinking category (either normal or low alcohol intake). The relative percentages for the other variables were delta Apo A-I 78%, delta HDL-C 82%, delta gamma GT 78% and delta MCV 76%. We conclude that Apo A-II may prove a valuable marker of alcohol intake in cross-sectional epidemiological studies, while delta Apo A-II may be a sensitive marker of change in alcohol intake in the prospective management of the heavy drinker. PMID- 2880598 TI - The biological role of hypothalamic hypophysiotropic neuropeptides. PMID- 2880599 TI - [Seroepidemiologic data on viral infections (HTLV-I and LAV/HTLV-III) in the Caribbean region and intertropical Africa]. AB - Since two years our laboratory is involved in the sero-epidemiology of retroviruses in Martinique, French Guiana and Equatorial Africa. French West Indies is an endemic area for HTLV-I with 3 to 5% positivity in blood donors. Such a prevalence increases with age in the general population, reaching 30% after 60 years of age. Data are given here regarding hematological and neurological syndromes observed in Martinique and associated with HTLV-I. Furthermore, we recently discovered an association between HTLV-I and the neuro myelopathy named endemic Tropical Spastic Paraparesis. Such an association has been confirmed in Jamaica, South West Japan and Ivory coast. French West Indies appeared quite free of LAV/HTLV-III in 1983/1984 but AIDS cases have been increasingly diagnosed in 1985. Recent data (early 1986) from the Blood Transfusion Center in Martinique (Dr. N. Monplaisir) indicate that 0.45% of blood donors have LAV/HTLV-III antibodies, as detected by the ELISA test. We present here a comparative view of preliminary prevalence data for LAV/HTLV-III in different areas of Equatorial Africa. PMID- 2880600 TI - Memory stages and brain asymmetry in chick learning. AB - Stages of formation of memory and the roles of different forebrain structures in memory formation were investigated by injecting various agents into the brains of chicks close to the time of peck-avoidance training. With L-glutamate injected bilaterally into the hyperstriatum 5 min pretraining, retention was good 1 min posttraining but significantly impaired at 5 min and each subsequent time point from 10 min to 24 hr. With ouabain, retention declined more slowly, showing significant impairment at 15 min and thereafter. With any of three protein synthesis inhibitors (anisomycin, cycloheximide, or emetine), retention was still good 60 min posttraining but significantly impaired at 90 min. The three time courses of decline of retention are consistent with hypotheses of three sequentially dependent stages of memory formation. Glutamate, ouabain, and emetine were found to affect only a restricted volume of tissue. Any of these three agents induced amnesia when injected into the left (but not the right) medial hyperstriatum ventrale or into the right (but not the left) lateral neostriatum; so it appears that both structures are required for formation of memory. Agents that are specific for a presumed stage of memory formation and whose action is restricted spatially should help reveal the roles of different brain structures in different stages of memory formation. PMID- 2880601 TI - [Regional and time-sequential changes in amino acid neurotransmitters after focal cerebral ischemia in the rat]. AB - Focal brain lesion is known to induce changes of blood flow and glucose metabolism in the areas other than the lesioned part itself. A well known example of this remote effect is so called diaschisis. To clarify the role of neurotransmitters in this phenomenon, amino acid neurotransmitters were measured in rat basal ganglia after middle cerebral artery occlusion. In the same ischemia model, blood flow and glucose metabolism have been reported to increase in the ipsilateral substantia nigra and globus pallidus in the postischemia period. Our results showed that GABA and aspartate were reduced in ipsilateral substantia nigra and globus pallidus from the 3rd day on, with glutamate level showing no significant change. In the contralateral substantia nigra, GABA increased significantly from the 1st day through the 28th day, whereas glutamate or aspartate showed no significant change. The same, although less pronounced, tendency was observed in the contralateral globus pallidus. In contralateral striatum, GABA increased only during the 1st week. These results may be interpreted as follows. GABA and aspartate were reduced in ipsilateral substantia nigra and globus pallidus due to the afferent pathway interruption caused by focal ischemia. The reduction of inhibitory GABA probably set neurons in these nuclei in a relatively activated state, resulting in the elevation of glucose metabolism and blood flow. Increment of GABA in contralateral substantia nigra and globus pallidus can be attributed to a compensation for the reduction inn ipsilateral nuclei, because the increment was observed even in a chronic phase. This hitherto unknown phenomenon will raise an interesting problem as to the plasticity of the damaged brain. PMID- 2880602 TI - Accurate detection of triple vessel disease in patients with exercise induced ST segment depression after infarction. AB - The severity of coronary artery disease is an important determinant of prognosis after acute myocardial infarction. The ability of a symptom limited exercise test to predict the presence of triple vessel disease was assessed in 221 patients three weeks after infarction. Coronary angiography was performed in patients with exercise induced ST segment depression. The presence of ST segment depression alone was poorly indicative of triple vessel disease; however, some specific features of ST segment changes on exercise were of predictive value. Downsloping ST segment configuration alone or horizontal ST segment depression associated with an early onset and a late recovery time after exercise correctly identified 30 (90%) of 33 patients with triple vessel disease whereas it incorrectly identified only 6 (15%) of 39 patients with single and double vessel disease. An abnormal blood pressure response was also predictive. In patients with ST segment depression after infarction triple vessel disease can be detected accurately by a combination of the electrocardiographic and haemodynamic variables attained on exercise. PMID- 2880603 TI - Immediate haemodynamic effects of a novel partial agonist, beta 1-adrenoceptor blocking drug ICI 141,292 after intravenous administration to healthy young volunteers and patients with ischaemic heart disease. AB - ICI 141,292 is a new beta 1-adrenoceptor blocking drug. The beta 1-adrenoceptor antagonistic effect of ICI 141,292 was examined in a double-blind, randomised crossover study in eight healthy young volunteers and compared with atenolol. Three doses of ICI 141,292 (1, 2 and 4 mg) and atenolol 5 mg were administered intravenously. The attenuation in exercise induced tachycardia varied between 16.0 and 21.2% (P less than 0.01). A significant reduction in blood pressure could be demonstrated following all three doses of ICI 141,292 and atenolol during exercise. At rest in the sitting position HR decreased approximately 8% following all three doses of ICI 141,292 and 14.9% after atenolol 5 mg. No changes in blood pressure were observed under resting conditions after any of the drugs. In six patients with ischaemic heart disease the intrinsic sympathomimetic activity following intravenous administration of four sequential doses (0.5, 0.5, 1.0 and 2.0 mg) of ICI 141,292 was examined. HR decreased 7% (P less than 0.05) following ICI 141,292 1 mg with no further decrease following the succeeding doses. Cardiac output decreased 5.2% (P less than 0.05) following a cumulative dose of 4 mg. No significant changes were observed in mean arterial blood pressure, stroke volume or total peripheral resistance whereas an increase in supine resting mean pulmonary arterial pressure of 3.4 mm Hg (P less than 0.05) could be demonstrated. ICI 141,292 seems to be a potent (at least five times as potent as atenolol) beta 1-adrenoceptor blocking agent possessing moderate intrinsic sympathomimetic activity. PMID- 2880605 TI - Possible involvement of the 29 kDa protein in H+-ATPase in the action of cationic uncoupler of oxidative phosphorylation. Effect of the (o-phenanthroline)2-Cu2+ complex as a cationic uncoupler. AB - The divalent cation (o-phenanthroline)2-Cu2+ complex was found to uncouple oxidative phosphorylation in mitochondria. Its uncoupling activity depended on inorganic phosphate (Pi) in the incubation medium, and was inhibited by the SH reagent N-ethylmaleimide, and retarded by ATP. The uncoupling by the (o phenanthroline)2-Cu2+ complex was suggested to be due to its modification of sulfhydryl groups in the 29 kDa protein in H+-ATPase. PMID- 2880606 TI - Engineering of the active site of human lysozyme: conversion of aspartic acid 53 to glutamic acid and tyrosine 63 to tryptophan or phenylalanine. AB - Three human lysozymes containing a mutation either at Asp-53 to Glu or at Tyr-63 to Trp or Phe were synthesized and examined for their immunological and enzymatical activities in comparison with the native one. All mutants were immunologically indistinguishable from native human lysozyme. The [Trp63] and [Phe63] mutants catalysed the hydrolysis of Micrococcus lysodeikticus cell wall and glycol chitin effectively, while the [Glu53] mutant displayed very low activity toward M. lysodeikticus cells and no detectable activity toward glycol chitin. PMID- 2880604 TI - Testicular cancer and antecedent diseases. AB - A case-control study of the aetiology of testicular cancer was conducted using information obtained by interview and from case-notes of 259 cases with testicular cancer and two sets of control patients -238 men with diagnoses other than testicular cancer attending the same radiotherapy centres as those attended by the cases, and 251 hospital in-patients not attending radiotherapy departments. Logistic regression analyses were performed, after stratifying by age and region of residence, to estimate the relative risks (RRs) associated with various aspects of prior medical history. The risk of testicular cancer was found to be raised for men with a history of cryptorchidism (RR based on comparison with all controls = 6.3; P less than 0.001), inguinal hernia (RR = 1.6; P = 0.14), mumps orchitis (RR = 12.7; P = 0.006), atopy (RR = 1.8; P = 0.03), and meningitis (RR = 3.0; P = 0.21). Inguinal herniorrhaphy before the age of 15 years was particularly a risk factor for seminoma, whereas the relative risks were similar for seminoma and teratoma for the other factors. The results add to the growing evidence that congenital abnormalities involving the process of testicular descent and closure of the processus vaginalis are risk factors for testicular cancer, and that some types of testicular damage later in life may also be important. The findings of associations with previous atopy and certain infections suggest a possible second aetiological mechanism - that immunological abnormalities may be associated with an increased risk of testis cancer. PMID- 2880607 TI - Regulation of Dictyostelium discoideum adenylate cyclase by manganese and adenosine analogs. AB - Adenylate cyclase is the critical enzyme in the chemotactic signal relay mechanism of the slime mold amoeba, Dictyostelium discoideum. However, few studies examining the regulation of this enzyme have been performed in vitro due to the instability of enzyme activity in crude lysates. For studies presented in this communication, a membrane preparation has been isolated that exhibits a high specific activity adenylate cyclase that is stable during storage at -70 degrees C and under assay conditions at 27 degrees C. The enzyme was activated by micromolar concentrations of MnCl2. GTP and its non-hydrolyzable analog, guanosine 5'-(beta, gamma-imino)triphosphate, inhibited the enzyme non competitively in the presence of either Mg2+ or Mn2+. However, this inhibition was more pronounced in the presence of Mn2+. Since guanylate cyclase activity in the D. discoideum membranes was less than 10% of the adenylate cyclase activity, there could not be a significant contribution by guanylate cyclase toward the production of cyclic AMP. Experiments indicate that D. discoideum adenylate cyclase was also regulated by adenosine analogs. The enzyme was inhibited by 2',5'-dideoxyadenosine and 2'-deoxyadenosine and inhibition was augmented by the presence of Mn2+. However, the inhibition was not entirely consistent with that which would be expected for the P-site of eukaryotic systems because some purine modified adenosine analogs also inhibited the enzyme. Guanine nucleotides had no effect on the inhibition by either purine-modified or ribose-modified adenosine analogs. The binding of cyclic AMP to its receptor on the D. discoideum membranes was not affected by either MnCl2 or adenosine analogs. PMID- 2880608 TI - Beta 2-adrenergic regulation of prostaglandin D2 receptor in rabbit platelets. AB - [3H]Prostaglandin D2 binding to rabbit platelets was increased by about 150% in the presence of beta-adrenoceptor agonist, isoproterenol. The isoproterenol induced potentiation of the [3H]prostaglandin D2 binding gave a bell-shaped dose response relationship (maximum response at 3 X 10(-8) M) in a stereospecific manner. Similar and moderate potentiation was obtained with terbutaline. On the other hand, beta-adrenoceptor antagonists such as alprenolol, propranolol and butoxamine (beta 2-specific) had no potentiating effect on [3H]prostaglandin D2 binding; rather, they abolished the isoproterenol-induced increase of [3H]prostaglandin D2 binding. The beta 1-specific antagonist, metoprolol, did not have any effect. Rabbit platelets were found to possess one [3H]prostaglandin D2 binding site (Kd = 6 X 10(-7) M, Bmax = 787 fmol/mg protein). In the presence of isoproterenol at 3 X 10(-8) M, Bmax was increased with unaltering Kd value. Isoproterenol did not increase [3H]prostaglandin E1, [3H]prostaglandin E2 and [3H]prostaglandin F2 alpha bindings to platelets. The potential effect of isoproterenol was mimicked by forskolin, theophylline, dibutyryl cyclic AMP, prostaglandin E1 and prostaglandin I2, but it was abolished by 2', 5' dideoxyadenosine, an inhibitor of adenylate cyclase, indicating that elevated level of cyclic AMP may be available for the induction of the increase of [3H]prostaglandin D2 binding. Prostaglandin D2-induced cyclic AMP synthesis and antiaggregation activity were also augmented in the presence of isoproterenol. These results suggest a beta 2-adrenoceptor-mediated cyclic AMP-dependent mechanism for the regulation of prostaglandin D2 receptor binding in rabbit platelets. PMID- 2880609 TI - Microtubule disruption enhances prostaglandin E2 production in osteoblastic cells. AB - Prostaglandins have been implicated in the response of bone to mechanical stimuli. To explore the potential role of the cytoskeleton in the control of prostaglandin production, we examined the effect of cytoskeleton disrupting agents on arachidonic acid metabolism in rat calvaria osteoblastic cells. We found that microtubule disrupting agents increase prostaglandin E production 4-5 fold. Stimulation was first detectable at 4 h and rose sharply between 4 and 8 h. 2 h exposure to 1 microM colchicine was sufficient to produce the maximum effect. Cytochalasin B at concentrations which caused marked shape changes had no effect on prostaglandin E production or on its stimulation by colchicine. Taxol, a stabilizer of microtubules, reduced the colchicine effect. The increase in prostaglandin E production was associated with enhanced conversion of arachidonic acid to prostaglandin E2 rather than enhanced release of arachidonic acid from phospholipids. This increase in enzymatic activity was not abolished by cycloheximide treatment at concentrations which inhibited 90% of protein synthesis in the cells. PMID- 2880611 TI - Sperm maturation in human semen: role of transglutaminase-mediated reactions. AB - A Ca2+-dependent, transglutaminase-like activity has been detected both free in the human seminal plasma and bound on the spermatozoon surface. A marked variability of the two enzymatic activities in the semen of different normal subjects was observed; but limited changes occurred in various ejaculates of the same individual. Moreover, we report evidence of the ability of several seminal plasma proteins to act as acyl donor substrates for endogenous transglutaminase, whereas human ejaculated spermatozoa have been shown to possess polyamine-binding sites specifically involved in transglutaminase-catalyzed reactions. It is postulated that semen transglutaminase may play a role in suppressing sperm antigenicity and in the male gamete's acquiring biological features of a fully differentiated and fertile cell. PMID- 2880610 TI - Biological markers in panic states: lactate-induced panic and mitral valve prolapse. AB - Anxious patients, and more specifically, patients experiencing panic attacks, are thought to have a significant biological component to their illness. This study looks at two promising biological markers associated with this patient population mitral valve prolapse and lactate-induced panic. We present our findings, which further characterize clinical and biological aspects of these two markers. PMID- 2880612 TI - The effect of diffusion on the trapping of membrane-bound receptors by localized coated pits. AB - Localized coated pits are considered in the primary steps of receptor-mediated endocytosis. According to the pit reinsertion mechanism, we have modified our previous kinetic model and studied the effect of diffusion on the trapping rate constant (k+). Using experimental data for low density lipoprotein (LDL) receptors on fibroblast cells, we found that the binding of receptors to coated pits is not totally diffusion controlled. For example, the process is less than 78% diffusion controlled if receptors are not allowed to escape the coated pits. However, due to the large uncertainties in the experimental parameters, a diffusion-controlled process cannot be ruled out. The greatest differences between localized and random reinsertion were found when the escaping rate constant (k-) is much greater than the rate constant for invagination of the pits (lambda 1). Under this condition, k+ for localized reinsertion is no less than 39% diffusion controlled, while k+ for random reinsertion shows no diffusion effect at all. PMID- 2880613 TI - [Muscarinic agonists do not alter the process of spontaneous quantum secretion of the mediator from motor nerve endings in the frog]. AB - The action of carbacholine (Cch) and muscarinic agonists--methylfurmethide, oxotremorine, metacholine, L- and D-F-2268 isomers on spontaneous quantum transmitter release was investigated in experiments on the frog sartorius muscle of R. temporaria. Cch decreased the frequency of miniature and plate potentials (mEEP) by 48%. The muscarinic agonists at a wide concentration range had no effect on mEEP frequency both in normal ionic medium and with potassium concentration increase to 10 mmol/l. The data obtained confirm the assumption that the inhibitory action of Cch on spontaneous transmitter release is unrelated to its muscarinic activity. It was concluded that muscarinic cholinoreceptors controlling spontaneous transmitter release are absent in the frog motor nerve terminals. PMID- 2880614 TI - Factor XIII A is synthesized and expressed on the surface of U937 cells and alveolar macrophages. AB - Factor XIII A subunit was detected in U937 cells and human alveolar macrophages by immunohistology and Western blotting. U937 cells synthesize factor XIII A subunit de novo under serum-free, platelet-free conditions, as indicated by 35S methionine labeling and immunoprecipitation. Thrombin-dependent activity was demonstrated to account for 98% of the total transglutaminase activity in U937 cells (1.5 micrograms per 0.5 X 10(6) cells/mL). Intact U937 cells and alveolar macrophages and homogenates from these cells cross-linked fibrin to form gamma gamma and alpha-polymers. Factor XIII A was detected on the surface of intact U937 cells and macrophages by flow cytometry and 125I-labeling and immunoprecipitation. Cell surface expression of factor XIII A was augmented in the presence of several soluble macrophage activators; however, no concurrent increase in its biosynthesis was observed. The presence and cell surface expression of factor XIII A subunit within macrophages suggest new pathways by which these cells may function in clotting and in the remodeling of the extracellular matrix during inflammation and wound healing. PMID- 2880615 TI - Factor XIIIa formation promoted by complexing of alpha-thrombin, fibrin, and plasma factor XIII. AB - Fibrin polymers (des A,B fibrinogen) reduced the concentration of alpha-thrombin required for 50% activation of plasma factor XIII (a2b2 tetramer) by approximately 100-fold. In the presence of fibrin, the amount of gamma-thrombin required for activation was not affected. Catalytically inactive i-Pr2P- and D Phe-Pro-Arg-CH2-alpha-thrombin were found to inhibit over 95% of the activation by alpha-thrombin in the presence of fibrin. Unlike plasma factor XIII, the concentration of alpha-thrombin required for 50% activation of platelet factor XIII (a2 dimer) was lower, and the activation was not enhanced by fibrin. However, when the a2 platelet factor XIII was incubated with purified b-chains, the alpha- and gamma-thrombin concentrations required for activation increased tenfold and reached levels similar to those required for activation of the plasma factor XIII. When fibrin was present, the alpha-thrombin concentrations needed for activation of the a2b2 complexes were reduced, and the presence of fibrin had no effect on gamma-thrombin cleavage of the a2b2 complexes. Therefore, the b chains must inhibit a-chain cleavage by alpha-thrombin in the absence of fibrin. These results imply that the formation of a cocomplex involving alpha-thrombin, fibrin, and plasma factor XIII causes some conformational change in plasma factor XIII such that the b-chains no longer inhibit cleavage of the a-chains. PMID- 2880616 TI - Molecular analysis of interferon-induced suppression of Philadelphia chromosome in patients with chronic myeloid leukemia. AB - Treatment with recombinant human interferon alpha-A (Roferon-A) is associated with stable suppression of the population of cells that display the Philadelphia (Ph1) chromosome in some patients with chronic myelogenous leukemia (CML) as defined by cytogenetic analysis. Southern blot analyses employing a 3' breakpoint cluster region (bcr) probe (Pr-1) were performed to confirm a complete suppression of the Ph1+ chromosome-positive clone of cells at the DNA level. The complete disappearance of rearranged restriction fragments of the bcr gene, which were a characteristic of the disease prior to Roferon-A therapy, was accompanied by the restoration of normal bone marrow and achievement of durable ongoing complete remission for 9 and 6 months, respectively, in two patients with Philadelphia-positive (Ph1+) CML. Molecular analysis is a valuable probe for monitoring the clinical course of disease in patients with Ph1+ CML. PMID- 2880617 TI - Aminogram of mouse skeletal muscle: deviations in response to repeated hexachlorophene treatment. PMID- 2880618 TI - Syrup of ipecacuanha: is it really useful? PMID- 2880619 TI - Treatment of cardiovascular diseases. PMID- 2880620 TI - Macrocytic anaemia in patients treated with sulphasalazine for rheumatoid arthritis. PMID- 2880621 TI - Interactions between noradrenaline and alpha 2-adrenoceptor agonists in the superior mesenteric arterial bed of the rat. AB - Interactions between alpha 2-agonists and noradrenaline vasoconstrictor responses were studied in the superior mesenteric arterial bed of the rat by use of perfusion both in situ with blood and in vitro with Krebs-Henseleit solution. Xylazine (1.9 X 10(-6) mol) administered into the perfusion circuit reduced the maximum response to noradrenaline in the in situ preparation by 35% and decreased the pD50 for noradrenaline from 8.5 +/- 0.01 to 7.9 +/- 0.13 (n = 7). Yohimbine (1 mg kg-1, i.v.) gave a small parallel shift in the noradrenaline log dose response curve and prevented the reduction in the maximum response by subsequent administration of xylazine. In vitro, xylazine (1.9 X 10(-6) mol) also gave a long-lasting reduction of 37% in the maximum response but did not affect the mid point sensitivity to noradrenaline. Yohimbine (10(-6) M) did not change either of these effects. Clonidine (1.9 X 10(-6) mol) did not affect the maximum response to noradrenaline in vitro but did reduce the pD50 from 7.72 +/- 0.17 to 6.9 +/- 0.17 (n = 6). Yohimbine did not change these effects. Guanfacine (1.8 X 10(-6) mol) had no effect on the sensitivity of the in vitro preparation to noradrenaline but did reduce the maximum response by 20%. Yohimbine (10(-6)M) prevented the depression of the maximum response. It is concluded xylazine and clonidine interfere with noradrenaline induced vasoconstriction only to a limited extent through their interaction with alpha 2-adrenoceptors and that some other, as yet uncharacterized mechanism which may be activated by their aryl amidine structure, is responsible for their in vitro effects. PMID- 2880622 TI - Triazolodiazepines: dissociation of their Paf (platelet activating factor) antagonistic and CNS activity. AB - The relationship between the activity of thieno- or benzo-triazolodiazepines on platelet-activating factor (Paf)-induced effects and on the CNS (central nervous system) was studied in vitro and in vivo. Brotizolam and triazolam inhibited Paf induced human platelet aggregation. The IC50 -values were 0.54 and 7.6 microM, respectively. This inhibitory effect was not blocked by the specific central-type benzodiazepine (BDZ) antagonist, Ro 15-1788, or the specific peripheral-type BDZ ligand, Ro 5-4846. These BDZ ligands also showed an inhibitory effect on Paf induced platelet aggregation (IC50 = 200 and 560 microM, respectively). Ro 15 1788 or Ro 5-4846 in combination with brotizolam or triazolam enhanced the Paf inhibitory effect of these triazolodiazepines. In guinea-pigs, Ro 15-1788, 100 mg kg-1 p.o. and 10 mg kg-1 i.v. completely inhibited the hypnogenic effect of 10 mg kg-1 p.o. and 1 mg kg-1 i.v. of brotizolam, respectively. Similar results were obtained with triazolam but at higher doses. In anaesthetized guinea-pigs, a dose of 100 mg kg-1 p.o. of Ro 15-1788 did not inhibit bronchoconstriction and hypotension caused by Paf (30 ng kg-1 min-1 i.v.). The combination of brotizolam (10 mg kg-1 p.o.) or triazolam (200 mg kg-1 p.o.) with this BDZ antagonist (100 and 400 mg kg-1 p.o., respectively) did not affect the Paf inhibitory activity of these triazolodiazepines. These results show that the Paf antagonistic properties of the triazolodiazepine can be dissociated from their CNS activity. It is conceivable that compounds of this structural type could be the forerunners of a novel series of potent Paf antagonists. PMID- 2880623 TI - The effect of nicotine on motoneurones of the immature rat spinal cord in vitro. AB - Nicotine [(-)-nicotine di(+)-tartrate 1-50 microM] produced depolarization of motoneurones as recorded from ventral roots of immature (1-5 day old) rat hemisected spinal cord preparations. This action of nicotine was accompanied by marked desensitization which persisted for at least 2 h following a 2 min application. Ventral roots sectioned from the spinal cord, which were sensitive to glycine, failed to respond to nicotine. Blockade of regenerative electrical activity with tetrodotoxin produced a mean reduction of 39% in the response to 10 microM nicotine. In order to avoid desensitization, blocking agents were tested for their ability to suppress the initial response to a 2 min application of 10 microM nicotine (0.58 mV +/- 0.07 s.e. mean, 21 preparations) in 4 or more naive preparations. Responses to nicotine (10 microM) were significantly reduced by 10 microM hexamethonium and were abolished by 250 microM hexamethonium but were resistant to the following antagonists:- atropine (1 microM), phentolamine (2 microM), strychnine (10 microM), kynurenic acid (2 mM) and a mixture of bicuculline (50 microM) and picrotoxin (50 microM). It is concluded that the depolarizing responses to nicotine may be due to the presence of nicotinic receptors either on the motoneurone membrane or on nerve terminals adjacent to motoneurones which release an unidentified neurotransmitter. PMID- 2880625 TI - Nicotine cue in rats: effects of central administration of ganglion-blocking drugs. AB - In rats trained to discriminate nicotine from saline, a single intraventricular injection of a small dose of the quaternary ganglion-blocking drug chlorisondamine blocked the response to nicotine for four weeks. pentolinium was only weakly active and hexamethonium was inactive as a nicotine antagonist under the conditions used, even in doses that were just below those producing myoclonic jerks. Chlorisondamine had no blocking effect in rats trained to discriminate the non-nicotinic drugs midazolam or morphine from saline. Intraventricular injections of chlorisondamine have a specific and unusually persistent nicotine blocking action, the mechanism of which requires further investigation. PMID- 2880624 TI - Paf-acether-induced death in mice: involvement of arachidonate metabolites and beta-adrenoceptors. AB - Intravenous Paf-acether (Paf, 15-80 micrograms kg-1) killed conscious Swiss mice in a dose-dependent manner, without causing platelet aggregation in the lung microvasculature, or pulmonary oedema. Propranolol (0.01-10 mg kg-1, i.p.) potentiated the effects of an LD20 of Paf dose-dependently, while the beta 1 adrenoceptor selective antagonist, metoprolol, was three orders of magnitude less potent in this respect. Salbutamol (1 mg kg-1, i.p.) provided complete protection against an LD80 of Paf. High doses of indomethacin, aspirin, benoxaprofen and FPL 55712 given i.p. failed to inhibit the effects of an LD80 of Paf, while BW 755C (50-100 mg kg-1) exerted a dose-dependent protection and benzydamine (50 mg kg-1) and nordihydroguaiaretic acid (200 mg kg-1) were partially active. Dexamethasone (1-5 mg kg-1, s.c.) exerted a dose-dependent protection, when administered at least 4 h before Paf. In mice anaesthetized with urethane, Paf (1-30 micrograms kg-1) produced hypotension which was not clearly dose-related. The effects of the highest dose were also tested on the resistance of the lungs to inflation and found to produce bronchoconstriction. It may be concluded that pharmacological manipulation of beta 2-adrenoceptors modulates Paf-induced death in mice, while arachidonate metabolites of the cyclo-oxygenase pathway and peptidoleukotrienes do not appear to be involved. However, lipoxygenase products, distinct from peptidoleukotrienes, may play a role in this phenomenon. It is suggested that bronchoconstriction, probably associated with cardiovascular effects, is a major determinant of the acute toxicity of Paf in mice. PMID- 2880626 TI - 1,4-Dithiothreitol-induced changes in histamine H1-agonist efficacy and affinity in the longitudinal smooth muscle of guinea-pig ileum. AB - The effect of 1,4-dithiothreitol (DTT) on histamine H1-receptor agonist affinity and efficacy has been investigated in longitudinal muscle strips of guinea-pig ileum. Exposure of ileal smooth muscle to DTT significantly increased the maximal responses to the partial agonists SKF71473 and DE-2PEA, indicative of an increase in agonist efficacy. This effect was paralleled by a small decrease in EC50 values. In contrast, DTT produced a parallel displacement of the concentration response curve to the full agonist histamine in the same muscle strips. Studies in which phenoxybenzamine and benzilylcholine mustard were used to reduce the maximum response to histamine suggested that DTT altered both agonist affinity and efficacy. The affinity constant for histamine, calculated by the method of Furchgott & Bursztyn (1967), increased by 2.7 fold in the presence of DTT. Furthermore, agonist efficacy also appeared to increase in the presence of DTT since the maximum response to histamine following phenoxybenzamine treatment increased on application of DTT. [3H]-mepyramine binding studies confirmed that DTT increased agonist affinity. DTT produced a significant parallel shift to the left of the displacement curves for histamine, 2-methylhistamine, 2 pyridylethylamine and 2-thiazolylethylamine. The results of this study therefore suggest that DTT potentiates H1-receptor-mediated contractile activity in guinea pig ileum by increasing both agonist efficacy and affinity. PMID- 2880629 TI - Follow-up of agoraphobic patients treated with exposure in vivo or applied relaxation. AB - The present study describes the results of a 7-month and a 15-month follow-up of 32 agoraphobic patients treated with exposure in vivo or applied relaxation. During the follow-up period, all patients were given self-exposure instructions. Assessments were made in three response systems--subjective-cognitive, behavioural, and physiological--at the follow-up points. The study showed overall maintenance of treatment results in all three response systems for exposure treated patients. For applied relaxation/self-exposure, there was a relapse on delta heart-rate at 7 months for physiologically reactive patients, but the improvement was regained at the 15 month follow-up. Furthermore, a large proportion of the total improvement occurred during the follow-up period: 36% and 22% for exposure and applied relaxation/self-exposure respectively. The proportion of patients reaching a clinically significant improvement was 50% at the end of treatment and 66% at the 15 month follow-up. PMID- 2880628 TI - Effects of alpha-adrenoceptor agonists on cardiac output and its regional distribution in the pithed rat. AB - Cardiac output, its distribution and tissue blood flows were determined with tracer microspheres in pithed rats during pressor responses elicited by either alpha 1-adrenoceptor agonists (cirazoline, phenylephrine) or alpha 2-adrenoceptor agonists (xylaxine, B-HT 933). Two doses were used for each of cirazoline and B HT 933 and phenylephrine was investigated in the presence of propranolol (3 mg kg 1). The rats were pithed under halothane anaesthesia. Cardiac output was increased by xylazine, the higher dose of B-HT 933 and phenylephrine. Heart rate was increased by phenylephrine and the higher doses of both cirazoline and B-HT 933. Stroke volume was greater in those groups given xylazine, phenylephrine and the higher dose of B-HT 933 but was decreased in those animals given the higher dose of cirazoline. Both alpha 2-adrenoceptor agonists increased the number of microspheres trapped in the lungs and the proportion of the cardiac output passing through the hepatic artery but decreased that flowing through the spleen and gastrointestinal tract. The higher dose of B-HT 933 also decreased the fraction of cardiac output flowing to the kidneys but kidney blood flow was maintained as a result of the increased cardiac output. Also, this treatment reduced blood flow in the epididimal fat pads. Both alpha 1-adrenoceptor agonists increased the fraction of cardiac output received by the coronary vasculature but the only other effect on distribution common to these agents was an increase in the percentage of the cardiac output passing to the hepatic artery. Cirazoline decreased the proportion of cardiac output distributed to the gastrointestinal tract and spleen but the total fraction of cardiac output passing to the hepatosplanchnic region was maintained as a result of the increase to the hepatic artery. Cirazoline markedly reduced the proportion of the cardiac output received by the kidneys and absolute flow in these organs was only 1.4% of control after the higher dose of this agonist but flow at the lower dose was maintained by the higher cardiac output. It is concluded that there is a significant contribution to the pressor responses elicited by alpha-agonists resulting from an alpha adrenoceptor-mediated increase in cardiac output that may result from greater heart rates or stroke volumes. Also, there is a differential distribution of alpha-receptor subtypes throughout the vasculature which is especially noticeable in the kidneys. PMID- 2880627 TI - Lack of involvement of alpha-adrenoceptors in sympathetic neural vasoconstriction in the hindquarters of the rabbit. AB - The hypothesis that sympathetic nerves in arterial blood vessels activate excitatory receptors distinct from alpha-adrenoceptors was investigated in vivo in the rabbit. In anaesthetized, ganglion-blocked rabbits, graded stimulation of the lumbar sympathetic nerve chains caused graded hind limb vasoconstriction. The responses to single pulses and short trains of stimuli were unaffected by benextramine (10 mg kg-1) and the longer trains were enhanced. Phenoxybenzamine (5 mg kg-1) slightly reduced the responses to short trains of stimuli and did not affect the responses to long trains. The dose-response curve to intra-arterial noradrenaline (after beta-adrenoceptor blockade) was shifted rightwards about ten fold by benextramine (10 mg kg-1) and by phenoxybenzamine (5 mg kg-1). In conscious rabbits the vasoconstriction caused by the nasopharyngeal reflex initiated by smoke inhalation was unaffected by benextramine (10 mg kg-1). Small mesenteric arteries (less than 250 microns) taken from untreated rabbits responded to noradrenaline with a threshold concentration of about 1 microM. Similar tissues from benextramine (10 mg kg-1)-treated rabbits were unresponsive to noradrenaline at concentrations up to 300 microM. However, these tissues were able to respond to potassium and angiotensin II. Aortic ring segments taken from the same rabbits were only about ten fold less sensitive to noradrenaline than segments from control rabbits. These results are in accord with the hypothesis that sympathetic nerves activate non-alpha-receptors in the vasculature of the rabbit. PMID- 2880630 TI - Late onset involuntary movements in chronic schizophrenia: relationship of 'tardive' dyskinesia to intellectual impairment and negative symptoms. AB - Intellectual impairment, negative symptoms, and medication history were assessed in chronic schizophrenic patients with and without abnormal involuntary movements (tardive dyskinesia). Patients with involuntary movements had received neither longer nor more intensive treatment with neuroleptics or anticholinergics. However, the presence or absence of involuntary movements was prominently associated with the presence or absence of intellectual impairment/negative symptoms; these features are characteristic of the defect state/type II syndrome of schizophrenia, in which structural abnormalities of the brain may be over represented. The role of subtle organic changes in conferring vulnerability to the emergence of such involuntary movements should be re-evaluated. PMID- 2880631 TI - The Nithsdale schizophrenia survey. V. Follow-up of tardive dyskinesia at 3 1/2 years. AB - The point-prevalence of tardive dyskinesia in schizophrenics from a discrete geographical area (Nithsdale, in Dumfries and Galloway Region) in 1981, 1982, and 1984 was 31%, 27%, and 30% respectively. This suggests that the prevalence of tardive dyskinesia in a community of schizophrenics has reached a plateau. In 12% of patients there was persistent dyskinesia, i.e. abnormal involuntary movements were present at all three assessments. Persistent dyskinesia was more common in older patients. The severity of tardive dyskinesia fluctuated between assessments in 41% of patients, indicating that it is only a transient feature in some cases. PMID- 2880632 TI - Sulphasalazine alone or in combination with D-penicillamine in rheumatoid arthritis. AB - Thirty patients (22 women) with active rheumatoid arthritis participated in an open study of 6 months' treatment with either enteric-coated sulphasalazine (SASP) or SASP plus D-penicillamine (DPA). Patients were assessed at regular intervals using a number of clinical and biochemical tests designed to detect specific antirheumatic activity. There were significant improvements in clinical and laboratory variables with both regimens consistent with second-line activity. Improvements were greater and more numerous with combination therapy. At the end of the trial period, there were nine 'responders' in the SASP/DPA group but only six in the SASP group. Neither efficacy nor toxicity could be related to patient acetylator status. Nausea and dyspepsia were frequent problems with both treatment regimens but dysgeusia and thrombocytopenia were confined to the SASP/DPA group. Study withdrawals were twice as common with combination therapy. These results suggest that a combination of SASP and DPA is more potent than SASP alone but at the expense of poorer patient tolerance. PMID- 2880633 TI - Perforated duodenal ulcer. PMID- 2880634 TI - The distribution of neurotransmitter-specific cells and fibers in the anteroventral periventricular nucleus: implications for the control of gonadotropin secretion in the rat. AB - The anteroventral periventricular nucleus (AVPv), which lies in the periventricular zone of the preoptic region, is critical for normal phasic gonadotropin secretion since lesions of this nucleus abolish the progesterone induced surge of luteinizing hormone secretion from the anterior pituitary, block ovulation, and induce persistent vaginal estrus in female rats. However, very little is known about the neurotransmitter-specific pathways associated with this nucleus. In the present study we evaluated the distribution of biochemically specific cells and fibers within the AVPv and adjacent regions by using an indirect immunohistochemical method with antisera to serotonin (5-HT), dopamine beta-hydroxylase (DBH), tyrosine hydroxylase (TH), neuropeptide Y (NPY), cholecystokinin-8 (CCK), vasoactive intestinal polypeptide (VIP), substance P (SP), neurotensin (NT), corticotropin-releasing factor (CRF), luteotropin releasing hormone (LRH), somatostatin (SS), thyrotropin-releasing hormone (TRH), oxytocin (OXY), vasopressin (VAS), adrenocorticotropic hormone (ACTH1-24), alpha melanocyte-stimulating hormone (alpha-MSH), leucine-enkephalin (L-ENK), and calcitonin gene-related peptide (CGRP). Our findings indicate that both cells and fibers containing these putative neurotransmitters are differentially distributed in and around the AVPv in accordance with the cytoarchitectonic organization of this part of the preoptic region. The AVPv itself appears to receive strong inputs from SP-, VAS-, CCK-, and SS-containing pathways, whereas the highest densities of L-ENK-, NT-, 5-HT-, NPY-, and DBH-immunoreactive fibers were found in the cell-sparse zone just lateral to the AVPv. The suprachiasmatic preoptic nucleus (PSCh), a small group of cells located ventral to the AVPv just dorsal to the optic chiasm, contained high densities of alpha-MSH- and ACTH-immunoreactive fibers, as well as substantial numbers of fibers containing catecholamines or NPY. In contrast, a dense plexus of VAS-stained fibers was distributed fairly evenly throughout the AVPv and PSCh. Numerous L-ENK-immunoreactive cell bodies, and moderate numbers of CCK-, NT-, and CRF-stained cell bodies were found in the AVPv. The PSCh contained many TH-stained cells (presumably dopaminergic), in addition to a moderate number of CCK-containing cell bodies, while a high density of NT- and CRF-stained cells were found in the cell-sparse zone lateral to the AVPv, in addition to several CCK-, SP-, VIP-, and TH-containing cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2880635 TI - Is glycine an inhibitory transmitter in rat lateral horn cells? AB - Spontaneous inhibitory postsynaptic potentials (IPSPs) and evoked IPSPs were recorded from a portion of lateral horn cells situated in thin transverse thoracolumbar spinal cord slices removed from neonatal rats. The IPSPs were reduced by hyperpolarization and inverted at membrane potentials between -65 and 75 mV. Strychnine but not bicuculline reversibly eliminated the IPSPs. The hyperpolarizations elicited by exogenously applied glycine exhibited electrophysiological and pharmacological characteristics similar to that of IPSPs. The results are consistent with the suggestion that glycine mediates an IPSP in a population of lateral horn cells. PMID- 2880636 TI - Are Ca2+-dependent proteases really responsible for Cl(-)-dependent and Ca2+ stimulated binding of [3H]glutamate in rat brain? AB - The role of Ca2+ ions in [3H]glutamate binding was re-examined using synaptic membranous preparations obtained from the rat brain. In vitro addition (0.1-5 mM) of calcium chloride exhibited a profound enhancement of the binding in a temperature-dependent manner, whereas that of calcium acetate had no significant effect on the binding independently of the incubation temperature. Calcium acetate elicited a significantly additional stimulation of the Cl(-)-induced and temperature-dependent facilitation of the binding. The augmentation by these two ions was invariably eliminated by the addition of an antagonist for the anion channels including picrotoxinin as well as of inhibitors of anion transport such as ethacrynic acid and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. L Aspartate exerted a more potent inhibitory action on the Cl(-)-dependent binding and Cl(-)-dependent and Ca2+-stimulated binding, than D-aspartate. The latter two bindings were selectively abolished by an agonist (quisqualic acid) and an antagonist (DL-2-amino-4-phosphonobutyric acid) for central glutamate receptors, respectively. It was also found that pretreatment of the membranes with calcium acetate resulted in a complete abolishment of the Ca2+-stimulated binding with a concomitant stimulation of the Cl(-)-dependent binding, which invariably occurred independently of the preincubation temperature (2 or 30 degrees C). No significant alteration was detected in the basal binding following the latter pretreatment. None of various protease inhibitors such as leupeptin, antipain, chymostatin and pepstatin induced a significant alteration in the basal, Cl(-) dependent, Ca2+-stimulated and Na+-dependent bindings of [3H]glutamate, respectively. These results suggest that Ca2+ ions may elicit their stimulatory action on the Cl(-)-dependent binding of [3H]glutamate even in the absence of Cl- ions added through the temperature-independent and apparently irreversible interaction with the anion transport carriers rather than the direct action on the binding sites of the ligand. The evidence presented here also suggests that the widely held view that Ca2+-dependent proteases are responsible for the exhibition of Cl(-)-dependent and Ca2+-stimulated binding of [3H]glutamate may need to be re-evaluated. PMID- 2880637 TI - Stimulation of both D1 and D2 dopamine receptors appears necessary for full expression of postsynaptic effects of dopamine agonists: a neurophysiological study. AB - The abilities of 4 dopamine agonists to inhibit the tonic single unit activity of substantia nigra dopamine neurons and stimulate tonic activity of globus pallidus neurons were compared to study the agonists' effects on pre- and postsynaptic dopamine receptors, respectively. The agonists studied were apomorphine and pergolide, which interact with both D1 and D2 receptors, and the selective D2 agonists quinpirole and RU 24926. Drugs were administered systemically. The 4 dopamine agonists were equipotent and equiefficacious at inhibiting the firing rates of dopamine neurons. In contrast, their effects on pallidal cells were not identical; apomorphine and pergolide induced significantly greater increases in pallidal cell activity than did quinpirole and RU 24926. In addition, pretreatment with a small dose of quinpirole did not attenuate the excitatory effect of apomorphine on globus pallidus cell activity, as low doses of apomorphine have previously been shown to do. Possible mechanisms underlying the differences in efficacy between the non-selective and D2 selective dopamine agonists in the globus pallidus were investigated. Coadministering quinpirole with apomorphine did not significantly attenuate the effect of apomorphine, suggesting that quinpirole is not a partial agonist at postsynaptic dopamine receptors. In addition, prazosin pretreatment did not attenuate the stimulatory effect of pergolide on firing rates of pallidal cells, indicating that the greater efficacy of the non-selective agonists was not due to concurrent stimulation of alpha 1 adrenergic receptors and dopamine receptors. However, the effect of quinpirole on pallidal cell activity was significantly potentiated by pretreatment with the D1 agonist RS-SKF 38393 but not its inactive enantiomer S SKF 38393. These results suggest that concurrent D1 and D2 receptor stimulation may be necessary for the full expression of postsynaptic receptor-mediated effects of dopamine and dopamine agonists in the basal ganglia. PMID- 2880638 TI - Biochemical evidence for glutamate and/or aspartate as neurotransmitters in fibers from the visual cortex to the lateral posterior thalamic nucleus (pulvinar) in rats. AB - The effects of visual cortex ablation on several neurotransmitter parameters in the lateral thalamic nucleus (pulvinar) in rats have been investigated. We found a 57% decrease in high affinity uptake of D-[3H]aspartate in the pulvinar after ablation of the ipsilateral visual cortex. The KCl-evoked release of exogenous D [3H]aspartate and endogenous glutamate were decreased by 33 and 37%, respectively. Moreover, the contents of endogenous glutamate and aspartate were decreased by 35%, each. The glutamate decarboxylase and choline acetyltransferase activities and the contents of other amino acids were not affected by the lesion. Our biochemical data indicate that glutamate and/or aspartate may be transmitters in the fibers from visual cortex to pulvinar in rats. PMID- 2880639 TI - Glutamate and picrotoxin injections into the preoptic basal forebrain initiate locomotion in the anesthetized rat. AB - This study determined the locomotor effects of glutamate and picrotoxin injections and electrical stimulation in the preoptic basal forebrain. Male rats, anesthetized with Nembutal, were held in a stereotaxic apparatus such that stepping rotated a wheel. Cathodal stimulation (0.5-ms pulses, 50-Hz frequency, 10-s train, less than 100 microA) was applied through a 30-gauge stainless-steel, insulated cannula to find locomotor sites. Glutamate (20 mM or 2 M) or picrotoxin (100 or 200 ng) were injected in volumes of 0.2 or 0.1 microliter of saline at a rate of 1 microliter/5 min. Electrical stimulation elicited locomotion (principally hindlimbs) in 32 sites which included the lateral and medial preoptic areas and the bed nucleus of the stria terminalis (BST). Stimulation in 23 sites, most in the BST and septal area, failed to produce locomotion. Stepping was elicited by glutamate and electrical stimulation in 15 sites. Glutamate was ineffective at 21 sites, at 6 of these sites electrical stimulation was effective. Longer bouts of locomotion were produced by 20 nM glutamate. Picrotoxin produced more intense and prolonged locomotion than glutamate. It was effective in 15 sites, at 12 of which electrical stimulation was also effective. At some ventral sites, picrotoxin-elicited stepping was continuous, at others it appeared in bursts of 5-20 s duration. At dorsal sites, the locomotor bursts were punctuated by episodes of pelvic flexion. Picrotoxin was ineffective at 12 sites, 7 of which were effective with electrical stimulation. These results indicate that activity of neurons in the preoptic basal forebrain can initiate locomotion. PMID- 2880640 TI - Progesterone alters GABA and glutamate responsiveness: a possible mechanism for its anxiolytic action. AB - In this study, the neuromodulatory effects of progesterone were tested in an intact neuronal circuit of a model extrahypothalamic CNS area. Spontaneous discharge and responses of single cerebellar Purkinje neurons to microiontophoretically applied gamma-aminobutyric acid (GABA) and glutamate were monitored before, during and after either systemic injection, at physiologic doses, or local application of the steroid. By both means of administration, progesterone significantly enhanced inhibitory responses of Purkinje cells to GABA and suppressed glutamate excitation within 3-10 min post-steroid. These results are consistent with the anxiolytic actions of the steroid. PMID- 2880642 TI - Electrophysiological and pharmacological actions of N-acetylaspartylglutamate intracellularly studied in cultured chick cerebellar neurons. AB - The electrophysiological and pharmacological actions of N-acetylaspartylglutamate (NAAG) in cultured chick cerebellar neurons were intracellularly investigated in comparison with L-aspartate (ASP) and L-glutamate (GLU). Iontophoretically applied NAAG dose-dependently induced depolarizations associated with increases in spike discharge and changes in membrane conductance. Relative excitatory potencies seemed to be GLU greater than ASP greater than or equal to NAAG. The voltage-dependent increase in input resistance observable in the presence of Mg ions was most notable for ASP, moderate for NAAG and least for GLU. The reversal potential of NAAG-induced depolarization was at about 0 mV and similar to that for ASP or GLU, indicating primary concern of Na+/K+-conductances to the NAAG action. Mg ions depressed the actions of ASP and NAAG more strongly than the GLU action. 2-Amino-5-phosphonovalerate (APV) and D-alpha-aminoadipate antagonized the actions of ASP and NAAG more effectively than the GLU action. 2-Amino-4 phosphonobutyrate (APB) and glutamic acid diethylester showed rather non selective antagonisms to NAAG, ASP and GLU. These results suggest that NAAG is excitatory to cultured chick cerebellar neurons and functionally resembles ASP or is intermediate between ASP and GLU, and may also support the suggested candidacy of NAAG for a neurotransmitter in the CNS. PMID- 2880643 TI - Alterations in responsiveness of noradrenergic neurons of the locus coeruleus in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. AB - Locus coeruleus may have a function in central blood pressure regulation and possibly in the pathogenesis of hypertension. In keeping with this notion, we have recently shown that deoxycorticosterone acetate (DOCA)-salt hypertensive rats demonstrate a greater increase in blood pressure induced by locus coeruleus stimulation than control animals. In an attempt to elucidate the underlying mechanisms leading to this alteration in responsiveness of the locus coeruleus, the sensitivity of noradrenergic neurons of the locus coeruleus to the transmitter candidates, epinephrine and glutamate, was investigated in DOCA prehypertensive (3 days post-DOCA), DOCA chronic hypertensive (6-8 weeks post DOCA) and control rats using conventional microiontophoretic and single cell recording techniques. Iontophoretically applied epinephrine produced a current dependent decrease in spontaneous firing rate of all noradrenergic neurons in both DOCA-treated and control rats. Locus coeruleus neurons of DOCA-treated rats at 3 days and 6-8 weeks were less sensitive to epinephrine than those of control rats and the magnitude of the depression in spontaneous firing rate was less. By contrast, iontophoretic applications of glutamate produced an increase in activity of all noradrenergic locus coeruleus neurons. However, there was minimal difference in glutamate sensitivity between neurons of DOCA and control rats. Since the changes in epinephrine sensitivity are apparent not only in the chronic stage but also in the prehypertensive stage, our findings suggest a potential role of the adrenergic input to the locus coeruleus in the pathogenesis of DOCA hypertension. PMID- 2880641 TI - Binding characteristics of [3H]opioid ligands to active opioid binding sites solubilized from rat brain membranes by glycodeoxycholate and NaCl: the recovery of binding activity by dilution. AB - This paper describes the binding properties of [3H]peptidergic opioid ligands to binding sites solubilized from rat brain membranes by the treatment with 0.125% sodium glycodeoxycholate and 1 M NaCl. The highest amount of the specific binding of [3H]-[D-Ala2-, Met5]enkephalinamide was obtainable when 10-fold diluted solubilized preparations were incubated in the presence of 0.1 mM MnCl2 and 100 mM NaCl at 0 degree C (on ice) for 3 h. With this assay condition, the significant binding of following [3H]opioid ligands, which have been thought to be selective for receptor types, was also observed: [3H]-[D-Ala2, MePhe4, Gly ol5]enkephalin (mu-type), [3H]-[D-Ala2, D-Leu5]enkephalin (delta-type) and [3H]dynorphin1-9 (kappa-type). The number of binding sites in solubilized preparations for each [3H]ligand corresponded to 40-50% recovery of original membrane-bound binding sites. The Scatchard plot of the concentration-saturation binding curve showed only one class of binding sites, with a high affinity for each [3H]ligand. Apparent dissociation constants between solubilized receptors and [3H]ligands were the same as membrane-bound ones, but the ligand specificity for each receptor-type, which was examined by binding inhibition tests with unlabeled ligands, decreased. Present results indicate that heterogeneous opioid receptors in rat brain membranes seem to be transformed into less heterogeneous forms through the treatment with glycodeoxycholate and NaCl and the dilution process. PMID- 2880644 TI - Increased enkephalin and dynorphin immunoreactivity in the hippocampus of seizure sensitive Mongolian gerbils. AB - Radioimmunochemistry (RIA) and immunocytochemistry (ICC) were used to measure proenkephalin and prodynorphin peptides in the brain of a genetic model of epilepsy, the seizure-sensitive (SS) Mongolian gerbil. Brain levels of both [Met5]- or [Leu5]-enkephalin (ME-LI) and dynorphin A1-8 and dynorphin A1-17 (DN LI) like immunoreactivity were increased in the hippocampal region of the SS gerbil. However, ME-LI and DN-LI did not follow the same patterns. ME-LI was significantly increased in the SS gerbils (post-seizure) compared to SR gerbils while ME-LI in SS (preseizure) gerbils was not significantly different from SR gerbils. DN-LI was significantly increased in the hippocampal region of both SS (preseizure) and SS (postseizure) gerbils compared to SR gerbils. These results strongly imply differences in the regulation of proenkephalin and prodynorphin metabolism in the Mongolian gerbil. The differences in metabolic regulation may signal fundamentally different roles of these opioid peptides in the modulation of seizure activity in this animal. PMID- 2880645 TI - Inhibition of gastric acid secretion by immunoneutralization of endogenous brain thyrotropin-releasing hormone. AB - Previous studies have shown that intracisternal (i.c.), but not intravenous administration of thyrotropin-releasing hormone (TRH), an endogenous tripeptide (pGlu-His-Pro-NH2), produces a time-, dose-dependent and vagus-mediated stimulation of acid secretion in rats. This study was designed to test the hypothesis that endogenous brain TRH plays a role in regulation of acid secretion in the pylorus-ligation model. In confirmation of previous reports, i.c. TRH (1 microgram) significantly (P less than 0.01) stimulated gastric acid output, gastric secretory volume and decreased gastric intraluminal pH. Intracerebroventricular (i.c.v.) infusion of TRH antiserum (anti-TRH) 30 min prior to pyloric occlusion significantly reduced acid output, secretory volume and raised gastric pH. This inhibitory gastric acid secretory response to i.c.v. anti-TRH appears to be specific since i.c.v. infusion of normal rabbit serum or antisera raised against neurotensin (NT), Leu-enkephalin (L-enk), gonadotropin releasing hormone (GnRH), somatostatin (SRIF) and alpha-melanocyte stimulating hormone (alpha-MSH) were without measurable effect. The findings of this study indicate that endogenous brain TRH, but not NT, L-enk, GnRH, SRIF or alpha-MSH plays a physiological role in regulation of acid secretion. PMID- 2880646 TI - Glutamine synthetase and energy metabolism enzymes in cultivated chick neurons and astrocytes: modulation by serum and hydrocortisone. AB - Primary cultures of astroglial cells and of neurons obtained from chick embryos were grown in culture medium with and without serum added. The expression of glutamine synthetase (GS) in the cultured nerve cells was investigated immunocytochemically and biochemically. The cellular localization of GS in cerebellar tissue sections and in cerebral cortex of chick embryos was investigated by immunohistochemical staining. In tissue sections the enzyme is only present in astrocytes and their processes; neurons and their structures do not express the enzyme. In contrast, in pure neuronal primary cultures, a high level of GS was detected by biochemical and immunochemical methods. Thus, our results clearly indicate the presence of GS in pure neuronal cell cultures and its absence in this type of cells in vivo. Removal of serum from the culture medium enhanced GS levels in primary astrocyte cultures, but was without effect on GS activity in neurons. Addition of calf serum to the culture medium induces a two-fold increase of cellular lactate dehydrogenase (LDH) activity in neurons by increasing specifically the M subunit containing isoenzymes. The sensitivity of chick astroglial cells and neurons toward the GS inducing effect of hydrocortisone and modulation of its effect by serum was also investigated. Differences in the sensitivity of the two types of nerve cells in culture toward the GS inducing effect of hydrocortisone, and the effect of serum could be demonstrated. PMID- 2880647 TI - [Precurarization: comparison between gallamine and vecuronium administered before suxamethonium]. PMID- 2880648 TI - Mechanisms of drug interactions of interest to dentists. PMID- 2880650 TI - False-positive results of confirmatory testing for antibody to HIV-I. PMID- 2880649 TI - Asthma: 2. Trends in pharmacologic therapy. AB - The most reasonable first therapy for ambulatory asthmatic patients is regular use of a selective beta 2-adrenoreceptor agonist administered with a metered-dose inhaler. When asthma is of more than mild severity, a second agent that acts through a different pharmacologic pathway is added. Although theophylline has traditionally been this second agent, recent concerns about its safety have prompted increasing use of inhalational agents such as corticosteroids, anticholinergics and mast cell stabilizers as appropriate second-line therapy. The use of such combination regimens and newer strategies such as high-dose inhaled corticosteroid therapy will reduce the proportion of patients who require systemic corticosteroid therapy for adequate control of asthma. The use of combination inhalational therapy also has a role in the management of asthma in the emergency department, the combination of a nebulized adrenoreceptor agonist and a nebulized anticholinergic being more effective than either agent alone in acute, severe asthma. The role of newer xanthine derivatives, antihistamines, calcium channel blockers and selective anti-inflammatory agents remains investigational. PMID- 2880651 TI - Principles of fracture management in children. PMID- 2880652 TI - Epiphyseal injuries of the foot and ankle. AB - A thorough knowledge of functional growth plate anatomy and physiology is essential to proper management of epiphyseal foot and ankle injuries. The ability to classify foot and ankle fractures according to the Salter-Harris anatomic and radiographic classification provides useful prognostic information that may affect treatment. The Dias-Tachdjian mechanistic classification system for pediatric ankle fractures provides useful information about the extent of osseous and soft tissue injury and the best method of closed reduction and correlates well with the Lauge-Hansen system, which is widely used for adult ankle fractures. Most epiphyseal foot fractures involve the metatarsals or phalanges and can usually be managed with closed reduction. Considerable spontaneous correction of deformity can be expected in the younger child (under age 10 years), but one should be aware that sagittal plane and rotational malalignment of the metatarsal heads may cause significant problems. Salter-Harris type I and II fractures of the ankle can usually be managed with closed reduction. Salter Harris type III and IV ankle fractures with greater than 2 mm of displacement require open reduction and internal fixation. One must also have a high index of suspicion for juvenile Tillaux and triplane transitional fractures that may not be obvious on plain radiographs. Although these fractures usually do not produce significant limb-length discrepancies, they are intra-articular fractures and ankle joint arthritis can result. Finally, younger children (under age 10 years) have a better prognosis for spontaneous correction of nongrowth arrest-induced deformities but a much poorer prognosis with growth arrest injuries than do older children, in whom growth arrest does not usually cause a significant problem. All children with growth plate injuries should be followed at regular intervals for at least 2 years or to skeletal maturity in the case of physeal disturbance. Treatment of epiphyseal fractures of the foot and ankle must be individualized but should always be based upon a thorough knowledge of anatomy, bone growth physiology, classification, potential pitfalls, and prognosis. PMID- 2880653 TI - Chemical restraint. AB - There are clinical and medico-legal implications to the forced administration of neuroleptic medication to actively resisting, aggressive psychiatric patients. However, there is little information on how frequently this occurs. This survey of its incidence on an acute admission ward demonstrates that "chemical restraint" as defined, is uncommon, considering the characteristics of this patient population. It is nearly always a response to threatened or actual violence towards others. The survey discovered, unexpectedly, that there were considerable differences in the actual measures used and in drug doses used during the event, between two wards of the same treatment unit. A prospective study might correlate the different patterns with degree of success, as well as address other questions, the resolution of which would lead to better quality of care. PMID- 2880654 TI - Cyproheptadine and drug-induced anorgasmia. PMID- 2880655 TI - Recombinant interferon beta and gamma in the treatment of adult T-cell leukemia. AB - Adult T-cell leukemia (ATL) is one of the most difficult diseases to treat because of severe underlying immune deficiency and metabolic disturbance. Interferon has potent antiviral, antiproliferative, and immunomodulating properties, and therefore, this may be a good agent to treat such immune deficient patients with peripheral T-cell leukemia. During a period from April 1984 to August 1985, six patients were treated with interferon-beta (IFN-beta), and interferon-gamma (IFN-gamma) was given to five patients. Three patients achieved partial remission by IFN-beta administration with a response duration of 1, 1.5, and 12 months respectively, whereas one complete remission and two partial responses were experienced by IFN-gamma treatment with 4, 4, and 2 months of response. Side effects of IFN-beta were similar to those of IFN-gamma including fever, chills, fatigue, mild hematologic depression, and transient hepatic enzyme abnormalities. These promising results warrant further well designed clinical trials including combination with other agents or modalities of treatment. PMID- 2880656 TI - Hypercalcemia and osteoclast proliferation in adult T-cell leukemia. AB - Eighteen autopsy cases of adult T-cell leukemia (ATL) were investigated clinicopathologically. Thirteen of the patients had hypercalcemia during their clinical course. Nine of the thirteen had a high level of serum calcium at the terminal stage, even after extensive chemotherapy. Microscopic examination of the bone revealed proliferation of osteoclasts and bone resorption in eight patients. No osteoclast proliferation or bone resorption was found in the other nine normocalcemic patients. The infiltration of ATL cells was observed in only two patients--one was hypercalcemic and the other, normocalcemic. The factors affecting the serum calcium level were examined in two hypercalcemic patients. Hypercalcemia could not be accounted for by parathyroid hormone or prostaglandins E levels, which were in the normal range, or by 25-hydroxyvitamin D and 1,25 dihydroxyvitamin D, which were low. Our findings are consistent with the mechanism proposed by several investigators, that the malignant T-lymphocytes produced an osteoclast-activating-factor-like substance that caused osteoclast proliferation and hypercalcemia. PMID- 2880657 TI - Observations on predicted brain influx rates of neurotransmitter precursors. Effects of tumor, operative stress with tumor removal, and postoperative TPN of varying amino acid compositions. AB - Effects of tumor, operative stress and tumor removal, and postoperative TPN of varying amino acid compositions on brain levels of tryptophan or tyrosine as predicted by their brain influx rates were studied in normals and in malnourished cancer patients. Concentrations of the large neutral amino acids (LNAA) were determined in patients before and after tumor removal, and in postoperative patients before and after receiving either a standard TPN solution (STD-TPN), or a branched-chain amino acid solution (BCAA-TPN). The LNAA were altered in all groups versus normals. Brain influx rates showed the following: in preoperative patients, predicted brain tryptophan levels were below normal (P less than 0.001), whereas tyrosine levels were within or above normal; no significant differences between pre- and postoperative tryptophan or tyrosine levels; postoperative STD-TPN did not change predicted brain tryptophan concentration from preinfusion values, but BCAA-TPN decreased it (P less than 0.001), underscoring the common transport carrier; and preinfusion predicted brain tyrosine levels were decreased (P less than 0.001) by both types of TPN solutions. These results imply low substrate levels for brain serotonin and catecholamine synthesis, possibly affecting functions dependent on their control. PMID- 2880658 TI - Detection of SSEA-1 on human renal tumors. AB - Stage-specific embryonic antigen-1 (SSEA-1) was localized on paraffin embedded, formalin fixed specimens of human renal tumors by immunoperoxidase staining using a monoclonal antibody. Of 19 renal cell carcinoma (RCC) samples tested, 12 were positive for SSEA-1; SSEA-1 was also found on distinct elements in two samples of Wilms' tumor. No correlation was found between expression of SSEA-1, and RCC morphology or pattern of growth. Because SSEA-1 is found on proximal tubules in the normal kidney, these results support the hypothesis that RCC arises from the cells of the proximal tubule. Furthermore, since greater than 60% of the RCCs examined expressed SSEA-1, this antigen may prove to be a useful target for immunolocation or therapy of metastatic RCC. PMID- 2880659 TI - Phenotypic modulation during tumorigenesis by clones of transformed rat liver epithelial cells. AB - From nine clonal subpopulations (strains) of chemically transformed cultured rat hepatic epithelial cells which were tumorigenic when implanted into 1-day-old isogeneic rats, a cell line was reestablished from each tumor and the cellular properties of the tumor-derived cell lines were compared to those of the corresponding progenitor cells that were implanted to produce the tumors. In seven of eight instances, the cellular DNA content of the tumor-derived cells was virtually identical to the DNA content of the respective progenitor cells, but in one case the tumor cells had twice as much DNA as did their progenitor cells. During the development of tumors in vivo, other cellular phenotypic properties often underwent considerable, but variable changes. These changes included the activity of gamma-glutamyl transpeptidase, the growth properties on plastic surfaces, and the expression of LDH isozymes. Although there was a relative enhancement in the ability of most of the tumor-derived cells to proliferate or to form colonies in calcium-poor medium, several tumor-derived cell lines had very low colony-forming efficiencies in media containing either normal or low levels of calcium. The most consistent association between phenotypes expressed in vitro and tumorigenicity was the ability of cells to form colonies in soft agar; all tumor-derived lines expressed this phenotype, and with some of them this phenotype was acquired only during the process of tumor formation in vivo. These results demonstrate that further phenotypic and genotypic alterations may occur in vivo during tumor formation by chemically transformed cultured cells following their implantation into isogeneic animals; and some of the alterations that occur in vivo may be necessary for the complete expression of tumorigenicity. Although anchorage-independent growth capacity cannot be used to predict the tumorigenicity of clones of rat liver epithelial cells chemically transformed in vitro, this growth property appears to be invariably induced prior to or during the formation of tumors in vivo by these cells. PMID- 2880660 TI - Direct inhibitory effects of somatostatin (analogues) on the growth of human breast cancer cells. AB - Various hormones and growth factors are involved in the growth regulation of breast (tumor) cells. In this report we show for the first time that an analogue of the neuropeptide somatostatin (Sandostatin) can also influence the proliferation of human breast cancer cells (MCF-7), namely, in an inhibitory fashion. With respect to dose-response relationship a bell-shaped curve was observed with the maximal inhibition of tumor cell growth at a sharply defined amount of Sandostatin (10 nM). The same effects were found with the natural hormone somatostatin-14 and another analogue (CGP 15-425). These results, together with the observation that high affinity binding sites for an iodinated derivative of Sandostatin are present in MCF-7 cells, support the conclusion that somatostatin and analogues act directly on breast cancer cells. PMID- 2880661 TI - Cell surface sialylation of two human tumor cell lines and its correlation with their platelet-activating activity. AB - The relationship between cell surface sialylation and platelet-activating activity was studied in two tumor cell lines of human origin, the SKNMC neuroblastoma line and the U87MG glioblastoma line. Their platelet-activating activity was evaluated in two different experimental systems, one that measures platelet aggregation and the other that quantifies platelet thrombus formation on vascular subendothelium under flow conditions. Our results demonstrate that, for the SKNMC line, the loss of 30% of surface sialic acid induced a significant reduction in its platelet-activating capacity. Upon recultivation desialylated SKNMC cells did not regenerate surface sialic acid and did not restore their initial values of platelet aggregation and platelet thrombus formation. Conversely, removal of 35% sialic acid from the surface of U87MG cells did not affect their pattern of platelet activation in either system tested. These results demonstrate that there is a correlation between cell surface sialylation and the capacity of SKNMC cells to activate platelets. The lack of effect of desialylation on U87MG-induced platelet activation indicates that different surface components may be the modulators of the interactions of these tumor cells with platelets. Our results support the hypothesis that heterologous mechanisms regulate platelet-tumor cell interactions and that tumor cell sialic acid may be only one of the aspects involved in such interactions. PMID- 2880662 TI - Influence of precursors on brain GABA level. PMID- 2880663 TI - Comparison of the immediate effects of two beta-blocking drugs: a nonselective and a cardioselective with modest ISA in exercise-induced angina. AB - To compare the effects of two beta-blocking drugs: a nonselective (propranolol) and a cardioselective with modest intrinsic sympathomimetic activity (visacor), 24 patients with stable angina pectoris performed a control exercise (without medication) on a bicycle ergometer (increments of 30 W every 3 min), and thereafter were randomized to receive either propranolol (40 mg t.i.d.) or visacor (200 mg once daily) for a 48-hour double-blind trial. The 2 groups on control exercise were similar with regard to their exercise tolerance: 7.6 +/- 2.3 versus 7.1 +/- 1.4 min (NS) and the behavior of heart rate, systolic, diastolic blood pressure and double product, at rest and during exercise. They exercised on the 2nd day 2 h after the intake of propranolol or visacor. In the 12 patients randomized to propranolol, heart rate, systolic and diastolic pressures, double product were significantly reduced at rest, compared with control exercise: 67 +/- 8 versus 81 +/- 10 beats/min (p less than 0.01), 132 +/- 20 versus 146 +/- 21 mm Hg (p less than 0.02), 80 +/- 8 versus 88 +/- 10 mm Hg (p less than 0.02), 8,828 +/- 1,927 versus 11,863 +/- 2,138 mm Hg X min-1 (p less than 0.001), respectively. On the contrary, in the 12 patients randomized to visacor, these parameters at rest were less modified and only heart rate was significantly decreased: 71 +/- 9 versus 81 +/- 11 beats/min (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2880664 TI - Spironolactone in the management of congestive cardiac failure: a review. PMID- 2880665 TI - Serum potassium and body weight during treatment with two fixed combinations of beta-blockers and diuretics in hypertensive patients: a controlled study. AB - Two fixed combinations of beta-blockers and diuretics, penbutolol plus furosemide and pindolol plus clopamide, were compared with respect to efficacy, safety, and tolerability in hypertensive out-patients. The two preparations were equally effective in reducing blood pressure when given as a single daily dose. Doubling the dosage for those patients who responded poorly did not improve therapeutic response. The group treated with pindolol-clopamide had a significant increase in mean body weight and a substantial decrease in serum potassium concentrations. No direct relationship between these findings could be demonstrated, but the loss of potassium would be an important consideration when treating patients who are particularly vulnerable to the consequences of hypokalemia. PMID- 2880666 TI - Analgesics in the management of acute pain. PMID- 2880667 TI - Segregation of FMRF amide-immunoreactive efferent fibers from NPY-immunoreactive amacrine cells in goldfish retina. AB - Immunocytochemical studies were conducted on goldfish to determine whether a retinal efferent fiber system, immunoreactive to the tetrapeptide Phe-Met-Arg-Phe NH2 (FMRFamide), might contain instead a substance similar to one of the 36-amino acid pancreatic polypeptides, the C-terminus of which is similar to FMRFamide. Our results demonstrate the presence of two separate peptidergic systems, one containing FMRFamide-like, and the other pancreatic polypeptide-like peptides. Antisera to FMRF amide reveal the efferent fibers, whose axons exit the optic nerve and terminate in layer 1 of the inner plexiform layer, as previously described. Antisera to porcine neuropeptide Y, and to avian and bovine pancreatic polypeptides label a sparse population of putative amacrine cell bodies and a dense fiber plexus in layers 1, 3, and 5 of the inner plexiform layer. Based on intensity of staining, this amacrine cell peptide appears to be most similar to neuropeptide-Y. Radioimmunoassay and immunocytochemical staining of retinas in which the efferent fiber peptide was depleted by optic nerve crush confirm in large part the observation that the two peptide systems are distinct. However, there is some cross-recognition of the FMRF amide-like tissue antigen by pancreatic polypeptide antibodies. Double-label studies with antisera to tyrosine hydroxylase and neuropeptide-Y indicate that the pancreatic polypeptide antigen is not co-localized with catecholamines. PMID- 2880669 TI - Total occlusion of the abdominal aorta in a patient with Takayasu's arteritis: the importance of lower rib notching in the differential diagnosis. PMID- 2880668 TI - Immunocytochemical localization and spatial relation to the adenohypophysis of a somatostatin-like and a corticotropin-releasing factor-like peptide in the brain of four amphibian species. AB - The distribution of somatostatin (SRIF) - and corticotropin-releasing factor (CRF)-like - immunoreactive material was studied in the brain of four amphibian species (Ambystoma mexicanum, Pleurodeles waltlii, Xenopus laevis, Rana ridibunda) by use of immunocytochemistry. A wide network of SRIF-immunoreactive fibers and numerous perikarya were observed in all amphibians examined, with a dense accumulation of nerve endings in the external layer of the median eminence (ELME). In the representatives of the four amphibian species the CRF-like system was more circumscribed. Immunoreactive perikarya were present in the preoptic area, mainly in a ventrobasal position, and in the interpeduncular nucleus. The tract running along the ventral part of the tuber cinereum ends in the ELME facing the rostroventral lobe of the pars distalis that contains corticotrophs. CRF fibers were scarce or absent in the neural lobe. In all species studied in the present work, CRF fibers end in the area of the ELME close to the pituitary lobe containing corticotrophs. This correlation is similar to that reported for the Japanese quail and several teleosts. PMID- 2880670 TI - A large inverted duplication allows homologous recombination between chromosomes heterozygous for the proximal t complex inversion. AB - We have examined the molecular organization of a region of mouse chromosome 17 that allows homologous recombination between wild-type and t haplotype chromosomes across a large inversion. We have used a combination of genetic mapping of restriction fragment length polymorphisms, molecular characterization of cloned regions isolated on overlapping cosmids, and subchromosomal restriction mapping using the pulsed field gel technique. Our analyses show that the wild type form of chromosome 17 contains an inverted duplication of an element of at least 650 kb that is present in only one copy in the t haplotype form. Two chromosomes, th45 and tAE5, arose by homologous recombination across the element that is present in both chromosomal variants in the same orientation. PMID- 2880671 TI - [Densitometric determination of desacetylmetipranolol in blood plasma]. PMID- 2880672 TI - [Treatment of hemorrhage of the upper gastro-intestinal tract with the Chinese drug hai huang san. Analysis of 50 cases]. PMID- 2880673 TI - [Our experience in the treatment of gastroduodenal hemorrhage with somatostatin]. AB - Somatostatin, a pituitary hormone with an inhibitory action on gastric secretion, has improved the therapeutic approach to the treatment of the hemorrhagic complications accompanying gastroduodenal ulcer. The authors report on their experience "in doppio cieco" with 84 patients, 53 of whom treated with somatostatin and 31 with cimetidine, the respective success rates being 96.6% and 90.32% in the two treatment groups. It was also noted that the somatostatin treated group showed earlier arrest of hemorrhage and a lower blood transfusion requirement. PMID- 2880674 TI - [Cryptorchism and surgery]. AB - Many different anatomical situations are observed by pediatric surgeons during the surgical procedure for cryptorchidism at any age. The authors propose an easy anatomical classification: type I seems to be a small trouble of the process of migration and to be more a disturbed fixation. Type III results from a big disturbed wolfian duct process. Type II is intermediary. A series of 102 cryptorchidism operated upon at the Pediatric Surgical depart. Children's Hospital Paris, were studied according to this classification and collorated with histopathological study. The correlation is significative. The authors suggest that this protocol of surgical description could be agreed by a lot of Pediatric surgeons, whatever be the age of patient at operation, in the purpose to allow a longitudinal study from initial anatomical disorders to spermogram and at last to bring a response to the unanswered question: what, when and how, a cryptorchidism has to be cured. PMID- 2880675 TI - [Spleno-gonadal fusion. Apropos of 3 case reports]. AB - Splenogonadal fusion is a very rare congenital anomaly, usually diagnosed during operation for other surgical conditions as inguinal during operation for other surgical conditions as inguinal hernia, testicular tumor, cryptorchism or epididymitis and discontinuous. In first form exists a link of splenic and connective-fibrous tissue between spleen and testicle. This string runs above the bowels, then through an inguinal canal and joins the testicle or surrounds the gonad. Surgical treatment consists of cutting of the cord from spleen and separating from albugineals coat of testicle. In discontinuous form numerous tubercles of splenic tissue situated near gonad are confirmed. Three own cases are presented. First case concerns a 4 year-old boy with diagnosis: tumor of testicle and left inguinal hernia. Splenic tissue surrounded testicle and separated it from epididymis. An attempt of separation of these masses from the testicle was unsuccessful and hemicastration was performed and removed 17 cm long cord attached to the spleen. There was no union between testicle and epididymis on micro- and macroscopic examination. Second case refers to a 8 year-old boy with left-sides cryptorchidism. During an operation 7 cm long string like rosary was removed. Last case: 12 year-old boy was treated with diagnosis of tumor of spermatic cord and suspicion of spleno-gonadal fusion. A 15 cm long string connecting upper pole of testicle and spleen was amputated. The embryology, the diagnosis and the treatment are discussed in both cases. PMID- 2880676 TI - [Prenatal diagnosis of mucoviscidosis: biochemical technics and studies of affected fetuses]. AB - The prenatal diagnosis of cystic fibrosis is based on microvillar enzymes values in amniotic fluid taken by amniocentesis at precisely the 17-18 weeks gestation age (15-16 weeks developmental age). In pregnancies with a cystic fibrosis affected fetus the values of the enzymes are depressed. Since microvillar enzymes are normal constituents of amniotic fluid, it is important 1. to have highly reproducible techniques and 2. to determine the range of the normal values and their variations in relation to the development of the fetus. Prenatal diagnosis was performed in more than 200 pregnancies with a 1 in 4 risk of cystic fibrosis and was based on significant modifications of 6 amniotic fluid enzymes values: gamma-glutamyl-transpeptidase, aminopeptidase and alkaline phosphatase (total and isoenzymes). Normal outcome was predicted in 135 pregnancies reaching term, 133 babies were normal and 2 were affected. On the basis of significantly abnormal enzymatic values an affected fetus was predicted in 57 pregnancies, 3 went to term, the infants were affected, 54 were terminated and the diagnosis of cystic fibrosis was confirmed in the examined fetuses. The decrease in amniotic fluid microvillar enzymes values is the result of an obstruction of the terminal ileum. Fetuses affected with cystic fibrosis developed an intestinal obstruction around the 15th week of developmental age which can be seen by ultrasound scanning in about fifty per cent of the cases. This obstruction persists in some fetuses and leads to a meconium ileus at birth. PMID- 2880679 TI - Medical therapy for silent myocardial ischemia. PMID- 2880677 TI - Carboplatin (CBDCA), iproplatin (CHIP), and high dose cisplatin in hypertonic saline evaluated for tubular nephrotoxicity. AB - We compared the acute tubular nephrotoxicity of three platinum compounds in children and adults with solid tumors by monitoring the urinary excretion of alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, and total protein. Cisplatin (100 mg/m2) was administered with mannitol, or at a twofold larger total dosage (50 mg/m2 per day for 4 days) in a 3% saline infusion. Carboplatin (300 mg/m2) was administered in combination with 5-fluorouracil, and iproplatin was administered in dosages ranging from 216 to 388 mg/m2. Enzymuria and proteinuria induced by cisplatin at a total dosage of 200 mg/m2 on a divided schedule did not significantly differ from that observed for the single 100 mg/m2 dose. Enzymuria and proteinuria induced by carboplatin and iproplatin were significantly less than that for cisplatin; however, one patient developed chronic tubular damage after three courses of carboplatin, and the acute tubular toxicity of iproplatin in one of 15 patients was exceptional. Our findings support the value of administering cisplatin in hypertonic saline on a divided schedule as a strategy to reduce acute tubular damage. Although carboplatin and iproplatin are less nephrotoxic than cisplatin, occasionally patients experience subclinical acute or chronic tubular damage that may lead to overt nephrotoxicity with continued therapy. PMID- 2880678 TI - Automaticity, triggered activity, and responses to adrenergic stimulation in cat subendocardial Purkinje fibers after healing of myocardial infarction. AB - We studied automaticity, triggered activity, and responses to alpha- and beta adrenergic stimulation in subendocardial Purkinje fibers overlying healed infarct scars (infarct preparation) and from remote normal zones (noninfarct preparation) of cat left ventricles. The preparations were studied 2 to 4 months after ligation of multiple distal tributaries of the left anterior descending and circumflex arteries. Subendocardial Purkinje fibers from corresponding areas of normal hearts served as control samples (control preparation). Transmembrane action potential characteristics and rates of automaticity (spontaneous phase 4 depolarization) did not differ among control, noninfarct, and infarct preparations. However, overdrive at cycle lengths of less than 400 msec suppressed automaticity to a greater degree in Purkinje fibers of infarct preparations than those of control and noninfarct preparations. Changes in automatic rate during superfusion with isoproterenol (10(-10)M to 10(-6)M) were not different among the three groups of preparations, but exposure to phenylephrine (10(-9)M to 10(-5)M) in the presence of 5 X 10(-7)M propranolol reduced the automatic rate to a greater degree in Purkinje fibers of infarct preparations than those of control or noninfarct preparations. Triggered activity arising from delayed afterdepolarizations was recorded in 10 of 29 infarct preparations (34%), but not in 12 control and 10 noninfarct preparations. These afterpotentials were augmented by increasing extracellular Ca++ concentration, 10(-7)M isoproterenol, and 10(-5)M phenylephrine in the presence of 5 X 10(-7)M propranolol. We conclude that Purkinje fibers overlying healed infarct scars have altered physiology of spontaneous automaticity, enhanced responses to alpha adrenergic interventions, and a tendency to triggered activity, and that both alpha- and beta-adrenergic effects may result in worsening of arrhythmias by augmentation of afterpotentials in healed myocardial infarction. PMID- 2880680 TI - Alanine aminopeptidase in serum: automated optimized assay, and effects of age, sex, smoking, and alcohol consumption in a selected population. AB - In the diagnosis of chronic (as opposed to acute) liver diseases, combinations of indicators are needed to improve specificity. Alanine aminopeptidase (AAP; microsomal aminopeptidase, EC 3.4.11.2) activity in serum reportedly is a very sensitive indicator of intrahepatic cholestasis and biliary obstruction; it is also particularly useful in diagnosing chronic liver disease when combined with an indicator of hepatocyte damage such as aspartate aminotransferase or alanine aminotransferase. We optimized the assay of AAP in serum, automated the assay by using a centrifugal analyzer, then used this automated assay to determine activity in 202 individuals, ages one to 73 years. The preliminary results were analyzed in terms of the effects of age, sex, smoking, and alcohol consumption on AAP activity in serum. Striking sex-related differences were observed: AAP activity in males declined 2.5 times more rapidly with age than did that in females; indeed, activity in adult females remained essentially constant. Moreover, AAP values were higher in men who smoked than in those who did not, the difference being of borderline significance by analysis of covariance (p = 0.0865) but significant by partial correlations (p = 0.02). No similar differences were seen for women smokers and non-smokers. When the effects of other variables were held constant, alcohol consumption alone did not significantly correlate with AAP activity in men or women. PMID- 2880681 TI - Thyrotropin-binding inhibitory immunoglobulin in patients with Graves' disease. Measurement and relationship to numeric abnormality of T cells. PMID- 2880682 TI - Immunoglobulin heavy chain switch region restriction fragment length polymorphisms are associated with renal disease. AB - We describe here, to our knowledge for the first time, associations between polymorphisms at the genomic DNA level in the immunoglobulin gene region and renal diseases which lead to chronic renal failure. Recent studies have shown that protein polymorphisms, present in immunoglobulin (Ig) heavy chains (Gm allotypes) are associated with certain forms of renal disease and with end stage renal failure per se. To investigate this association at the DNA level we have used probes which recognize Ig heavy chain genes and this report describes results obtained with one of these, the S mu switch region probe. With the restriction endonuclease Sst 1 (or the isoschizomer; Sac I) a number of restriction fragment length polymorphisms (RFLP) can be obtained which are recognized by this probe and there is a highly significant association between certain of these and renal disease. This is the first report of Ig switch region polymorphisms being associated with disease, yet our results suggest that S mu RFLP are more closely linked to renal disease than Ig protein polymorphisms. PMID- 2880683 TI - Thyroid stimulating immunoglobulin (TSI) synthesis by pokeweed mitogen (PWM) stimulated peripheral blood lymphocytes (PBL) from Graves' disease (GD) patients. AB - Lymphocytes from freshly diagnosed untreated GD patients can be induced to produce in-vitro IgG, and more precisely TSI in the presence of PWM, a T cell dependent polyclonal activator of B cells. TSI were measured from days 8 to 41 of culture, using a functional cAMP production assay, after the deposition of culture supernatants on HTEC. Spontaneous or PWM induced IgG synthesis was optimal on day 28 of culture for GD MNC, with amounts of IgG in PWM stimulated GD culture supernatants twice those found in unstimulated GD MNC. Moreover only PWM stimulated GD MNC produce IgG which induce cAMP production by cultured HTEC, with a significant correlation between in-vitro IgG and cAMP levels. PMID- 2880684 TI - Comparative effects of calcium-channel blockers and beta-adrenergic blocker on early diastolic time intervals and A-wave ratio in patients with hypertrophic cardiomyopathy. AB - To compare the effects of calcium-channel blockers with those of beta-adrenergic blockers in patients with hypertrophic cardiomyopathy (HCM), diastolic time intervals (IIA-O time, from the second heart sound to the O point of apexcardiogram, IIA-MVO time, from IIA to the mitral valve opening, and MVO-O time, from the MVO to the O point of apexcardiogram), and A-wave ratio measured from apexcardiogram were evaluated before and after more than three months of treatment. In both groups, heart rate significantly decreased after treatment. The IIA-MVO time was not affected by either drug. The IIA-O and the MVO-O times were significantly shortened by calcium-channel blockers (from 234.6 +/- 77.4 ms to 204.6 +/- 39.2 ms; p less than 0.01, and from 133.1 +/- 66.4 ms to 100.3 +/- 34.0 ms; p less than 0.01, respectively). However, they were not affected by beta adrenergic blocker. A-wave ratio significantly decreased after calcium-channel blockers (from 18.0 +/- 9.8% to 13.7 +/- 7.3%; p less than 0.01) and beta adrenergic blocker (from 21.7 +/- 12.6% to 17.2 +/- 8.0%; p less than 0.01). From these observations, it is suggested tht calcium-channel blockers improved the early diastolic filling rate, whereas beta-adrenergic blocker did not affect it. It is concluded that the effects of calcium-channel blockers and beta-adrengergic blocker on early diastolic time intervals were different in patients with HCM. PMID- 2880685 TI - Therapeutic trends in the management of patients with acute myocardial infarction (1975-1984): the Worcester Heart Attack Study. AB - As part of an ongoing community-wide study of time trends in the incidence and case-fatality rates of patients hospitalized with acute myocardial infarction (MI) in all 16 Worcester, Massachusetts, metropolitan hospitals during the years 1975, 1978, 1981, and 1984, changes over time in the therapeutic management of 3263 patients with validated acute myocardial infarction were examined. Beta blocker (21%, 1975; 52%, 1984) and nitrate (56%, 1975; 93%, 1984) therapy use increased dramatically over time. Use of antiplatelet agents was inconsistent over time, while use of digoxin remained stable, being used in approximately 40% of all patients over the four periods studied. Use of antiarrhythmic medications other than lidocaine decreased consistently over time (31%, 1975; 22%, 1984). Lidocaine use increased between 1975 (31%) and 1978 (52%) and then leveled off to being used in approximately 45% of hospitalized patients with acute MI in 1981 and 1984. A variety of demographic (e.g., age, sex, teaching hospital) and clinical characteristics (e.g., MI order, MI type, MI location, peak CPK findings, occurrence of acute clinical complications) were also associated with the use of these therapies for the combined study periods. The results of this population-based study suggest considerable changes over time in the therapeutic management of patients hospitalized with acute myocardial infarction and of numerous patient demographic and clinical factors associated with their use. PMID- 2880686 TI - Systemic mastocytosis: management of an unusual case with histamine (H1 and H2) antagonists and cyclooxygenase inhibition. AB - A patient with urticaria pigmentosa and systemic mastocytosis developed hypotension following indomethacin administration. He then developed further episodes not related to indomethacin. Based upon the experience of others with the management of patients with systemic mastocytosis who showed exceptional reaction to cyclooxygenase inhibition, it was decided to treat him with H1 and H2 blockade followed by aspirin, another cyclooxygenase inhibitor. The procedure was carried out under careful observation with cardiac monitoring. After 160 mg of aspirin, he developed hypotension, tachycardia, and flushing accompanied by difficulty of breathing and headache. A vasoconstrictor drug (levarterenol) was administered. The patient's symptoms subsided, and after 1 hour aspirin was again administered, this time with no side effects. The dosage was increased to 975 mg every 6 hours, and he has had no further hypotensive episodes on this regime for 2 years. Cyclooxygenase inhibition, combined with H1 and H2 blockade, is an effective treatment for this condition, but for these patients initiation of aspirin therapy should be carried out with extreme care. PMID- 2880687 TI - The effect of acetaminophen on the disposition of fenoldopam: competition for sulfation. AB - Both fenoldopam and acetaminophen undergo conjugation with sulfate in humans. The present study was undertaken to determine if a metabolic interaction exists between these two compounds in humans. Twelve healthy male volunteers participated in a single-dose crossover study with 100 mg fenoldopam (capsule) alone or in combination with 1000 mg acetaminophen. The effects of chronic acetaminophen dosing (1000 mg three times/day for 7 days) on a single 100 mg tablet of fenoldopam were studied in a second crossover study in seven additional volunteers. Concomitant dosing with fenoldopam with acetaminophen resulted in increases in peak fenoldopam plasma concentration and AUC after both single (+32% and +50%, respectively) and chronic (+73% and +66%, respectively) acetaminophen dosing. Decreases in peak plasma concentrations and AUC for fenoldopam's sulfated metabolites were seen in both studies. These findings indicate a metabolic basis for the interaction between fenoldopam and acetaminophen, presumably through a competition for inorganic sulfate. PMID- 2880688 TI - The effect of fenoldopam, a dopaminergic agonist, on renal hemodynamics. AB - Fenoldopam, a dopaminergic agonist, was administered intravenously to 18 healthy male subjects in doses ranging from 0.025 to 1.0 microgram/kg/min for 2 hours. Three subjects were studied in a three-way crossover of fenoldopam at doses of 0.025, 0.10, and 0.50 microgram/kg/min. Fenoldopam decreased diastolic blood pressure and increased pulse rate without changing systolic blood pressure. Fenoldopam produced dose-related increases in para-aminohippuric acid clearance up to 75% at the 0.50 microgram/kg/min dose. This increase in renal blood flow was accompanied by increases in urine volume, water, and solute excretion; glomerular filtration rate was unchanged. Doses greater than 0.25 microgram/kg/min caused flushing and nasal congestion. The dopamine receptor antagonist metoclopramide (0.1 mg/kg/hr) did not block the systemic hemodynamic effects of fenoldopam but attenuated the increase in para-aminohippuric acid clearance. Fenoldopam plasma levels achieved steady state between 30 and 120 minutes after the start of the infusion and were linear with respect to infusion rate. Our findings show that intravenous fenoldopam causes systemic arteriolar vasodilation, accompanied by renal vasodilation and increased sodium excretion. PMID- 2880690 TI - Differences between somatostatin-28 and somatostatin-14 with respect to their biological effects in healthy humans and acromegalics. AB - In order to compare the effects of somatostatin-28 (SS-28) with those of somatostatin-14 (SS-14) in humans, we administered both compounds randomly in 5 healthy persons and 3 patients with active acromegaly. Blood glucose, growth hormone, insulin, glucagon, TSH, FSH, LH and prolactin were estimated after arginine, TRH and LHRH stimulation in the normals and without stimulation in the acromegalics. Both substances were administered in doses of 25, 50, 200 and 250 micrograms. Our results indicate that SS-28 is at least 5 times more potent in man than SS-14 as far as inhibition of growth hormone, insulin, glucagon and prolactin secretion is concerned. On the other hand SS-28 is at least 2 times more potent than SS-14 in the inhibition of TSH, FSH and LH. If this difference in potency is calculated on the basis of equimolarity, the action of SS-28 becomes even much greater. According to these findings, SS-28 appears to be either the main hormone and SS-14 a fragment of it with a lesser degree of biologic activity, or the prohormone with special properties. PMID- 2880689 TI - Effects of indenolol on blood pressure, lower limb blood flow, adrenergic reflexes, and plasma renin activity. AB - The antihypertensive effects of indenolol, a new not-cardioselective beta blocking agent, were evaluated in patients with WHO grades I and II essential hypertension (range 160/95 to 200/115 mm Hg) in a double-blind, placebo controlled study after acute (12 patients) and 2-week treatment (seven patients). Indenolol (30 to 120 mg) reduced blood pressure in a dose-dependent fashion. Maximum reduction was 26 mm Hg for systolic and 17 mm Hg for diastolic pressure. Hypotensive activity commenced within 10 minutes, peaked in 60 minutes, and persisted for about 7 hours. Lower limb vascular resistance (strain-gauge plethysmography) was significantly lowered, thus suggesting an intrinsic sympathomimetic activity. Heart rate was progressively reduced at 30 and 60 mg without any additional effect at 120 mg. Indenolol did not alter adrenergic reflexes (standing, cold application, and hand-grip) and did not induce any side effect. In conclusion, indenolol possesses an antihypertensive activity associated with reduction of vascular resistance. PMID- 2880691 TI - Takayasu's arteritis--a special form of the aortic arch syndrome. Manifestations of a chronical type III. AB - The case of a 45-year-old woman with arteritis of Takayasu's type is reported. This disease belongs to the inflammatory diseases of the aortic arch and sometimes shows extensive calcifications of the arterial system. The diagnosis is based on typical anamnesis and characteristic clinical symptoms, as well as on radiologic findings. The clinical signs depend on the extension of the disease. The literature about this rare disease is discussed. PMID- 2880692 TI - Oral absorption of the somatostatin analogue SMS 201-995: theoretical and practical implications. AB - Oral administration of SMS 201-995 (SMS), a subcutaneously injectable somatostatin analogue, was investigated in five healthy volunteers, who drank 2 mg of SMS with 75 g of glucose. Mean maximal plasma SMS concentrations after the 2 mg oral dose were comparable with those after subcutaneous injection of 50 micrograms, although the peak was delayed (90 vs 15 min). Biological activity of absorbed SMS was shown by significant and lasting suppression of plasma insulin concentrations, resulting in significant hyperglycaemia at 90 and 120 min compared with the control study. The feasibility of oral administration of SMS may extend its use in the treatment of acromegaly and gut endocrine tumours. Other peptide hormone analogues, structurally 'protected' against enzymatic degradation, may also be active orally and thus be useful therapeutically. PMID- 2880693 TI - Takayasu's arteritis: a pathogenetic role for cytotoxic T lymphocytes? AB - Takayasu's arteritis is an inflammatory panarteritis of unknown aetiology affecting large elastic arteries. We examined a segment of abnormal common carotid artery removed at by-pass surgery from a 23-year-old man with typical angiographic features of Takayasu's arteritis. Using monoclonal antibodies we were able to demonstrate marked infiltration of the arterial wall with OKT8 positive lymphocytes (suppressor/cytotoxic cells) but not with OKT4 positive lymphocytes (helper cells). Studies of circulating lymphocytes showed increased numbers of "activated" cells and increased in vitro cytotoxicity against cultured human umbilical cord endothelial cells, compared to normal lymphocytes. Cellular immunological mechanisms may play an important role in the pathogenesis of Takayasu's arteritis, possibly through the direct action of cytotoxic T cells on large elastic arteries. PMID- 2880694 TI - Pipothiazine palmitate: a versatile, sustained-action neuroleptic in psychiatric practice. AB - A study lasting 1 year assessed the effectiveness and tolerance of depot neuroleptic treatment with pipothiazine palmitate in 52 patients suffering from schizophrenia or related conditions (17 acute and 35 chronic). A 100 mg dose was given to 31 patients and 50 mg to 21 patients: 40 patients received injections 4 weekly, 8 patients 3-weekly and 4 patients 2-weekly. Duration of treatment ranged from 3 to 12 months, involving a total of 347 patient-months. The significant improvement produced by pipothiazine palmitate as shown by patient assessment, based on the Parkside Behaviour Rating Scale (p less than 0.05), a Hamilton-based affect scale (p less than 0.05) and a global rating scale of affect and psychomotor activity (p less than 0.01). Most target symptoms were relieved. A particularly favourable affective response was noted. The incidence of adverse reactions was low and did not present major problems; 6 cases of dystonic reaction were seen, but dealt with promptly and effectively. PMID- 2880695 TI - [Humoral immune responses to stages of Brugia pahangi in experimentally infected rats]. AB - In the present experiment, Sprague-Dawley rats were inoculated with Brugia pahangi, a lymphatic dwelling filarial parasite. Each rat received 100 third stage larvae (L3) of B. pahangi freshly harvested from Aedes togoi. Rats in the control group were injected with saline. After inoculation, tail vein blood was collected from each rat at 2-week intervals. The immune responses of the infected rats to B. pahangi were measured by the enzyme-linked immunosorbent assay (ELISA). Four types of antigen were prepared from different stages of B. pahangi. The antigen extracts were prepared from microfilaria, L3, and male and female adult worms by homogenization, eight times of freezing and thawing, and centrifugation at 11,000 X g for 45 min at 4 degrees C. Aliquots of supernatant extracts were stored at -20 degrees C. These antigens were adjusted to the same concentration of their protein contents and employed in the ELISA test. Serial serum dilutions were made to determine the concentrations of stage-specific antibodies in each serum sample collected during the infection course. Microfilaria specific antibodies appeared in the blood of infected rats at the 6th week of infection. Peak titer was observed at the 10th week. Subsequently, a gradual decrease was seen in the following month. Serum antibody titers against L3 and adult antigens rised since the 4th week and reached to the peak at 14th week. The exist of common antigens shared by the mature adults and infective larvae were detected by the ELISA and conformed by disc gel electrophoresis. PMID- 2880696 TI - [Dengue vector density survey in Liuchiu, Pintung, Taiwan]. AB - The first outbreak of dengue in Taiwan in 35 years was recorded in the summer of 1981 in Liuchiu, Pintung, a small offshore island of southern Taiwan. An investigation team visited the affected area during the period of 14-17 October 1981 and collected 8,641 mosquito larvae, of which 4,432 were Aedes aegypti and 4,182 were Ae. albopictus. The house index, container index and Breteau index were 44.2, 23.9 and 73.0 for Ae. aegypti and 41.3, 17.0 and 51.9 for Ae. albopictus, respectively. Both species of mosquitoes are peridomestic breeders, with larvae found in water-holding containers in or outside houses. Ae. albopictus is indigenous, but Ae. aegypti may be of recent introduction to the island. As the two species are closely related, the larvae of both species were found co-existent in only 2.3% of positive containers. This supports the hypothesis of the "competitive exclusion principle", i.e., competition is possibly occurring on this island. PMID- 2880697 TI - [A new instrument for preparing the mammary artery for coronary revascularization]. PMID- 2880698 TI - Modelling prey-predator cycles using hemipteran predators of mosquito larvae for reducing world-wide mosquito-borne disease incidence. AB - Diplonychus indicus is an aquatic hemipterous bug known to be a voracious predator of dipteran larvae, among others, and to show a selective predation for mosquito larvae when exposed to a mixed prey diet. A datum consisted of the percentage of the fourth instar of (25) culicine mosquitoes killed by the bug. Data around the clock, published earlier (from starved adult males of this bug), reanalyzed by single cosinor, reveal a circasemidian rhythm (p = 0.004). This result prompts the recommendation of studying the time structure of prey-predator cycles further to evaluate the merits or demerits of introducing the bug in the field with the aim of reducing worldwide mosquito-borne disease incidence. PMID- 2880699 TI - Causes of changes in brain noradrenaline systems and later effects on responses to social stressors in rhesus monkeys: the cascade hypothesis. AB - Disruption of social attachments in social primates produces a protest-despair response. In rhesus monkeys, the response is probably adaptive in the feral environment, although the despair stage resembles human depression in many respects. The severity of the response varies between individuals and is affected by deprivation of certain classes of social stimuli during development. Social deprivation is associated with differences in the concentrations of noradrenaline (NA) in cerebrospinal fluid and in responses to agents that affect catecholamine systems. Thus, early rearing conditions and pre-existing genetic or perinatal differences between monkeys can have long-term effects on the response to social separation, and NA system release and/or receptor mechanisms are involved. NA systems appear to mediate adaptation to the environment from the level of perception to reorganization of neural tissue. Adaptation to the social environment may involve a cascade of changes that begins with behavioural coping attempts and terminates in structural reorganization of regions of the cerebral cortex. Processes at each level occur within environmentally appropriate but neurobiologically constrained time-frames. The cerebral NA system may be an adaptive mechanism that can fail or be damaged. Behavioural changes caused by such damage or failure would be manifested by inappropriate responses to environmental contingencies and inability to change behaviour to adapt to the prevailing environment. These features of NA system disorder could be common to depression and several other forms of human psychopathology. PMID- 2880700 TI - [Clinical use of island skin-flaps]. PMID- 2880701 TI - Alpha-adrenergic system in the modulation of pancreatic A and B cell function in normal rats. AB - The role of the alpha-adrenergic system in the control of pancreatic A and B cell function was investigated in an isolated perfused rat pancreas model. Two experimental procedures were performed. In the first one we evaluated the effects of two distinct concentrations (10(-8) M and 10(-7) M) of five adrenergic substances, with varying degrees of potency on the alpha-adrenergic presynaptic receptor, on insulin (IRI) and glucagon (IRG) release induced by arginine (20 mM) plus glucose (6.6 mM). In the second procedure we studied the effects of the two alpha-blocking agents yohimbine (alpha 2-blocker) and prazosin (alpha 1-blocker) at 10(-7) M on epinephrine-modulated IRI and IRG response to the same combined metabolic stimulus. The inhibitory activity on basal and metabolically induced IRI secretion of the agonists was superimposable on their potency on the presynaptic alpha 2-adrenergic receptors. Similarly, the alpha 1-blocking agent prazosin was less effective than the alpha 2-blocker yohimbine in counteracting the inhibitory effects of epinephrine on basal and arginine plus glucose-induced insulin release. The alpha-cell activity was clearly stimulated by epinephrine, whereas selective alpha-adrenergic drugs showed no significant action on IRG secretion. Both alpha-blockers were ineffective on basal IRG release, while they had some potentiating effect on the epinephrine-induced glucagon release in basal state and during the metabolic stimulus, without a significant difference between the two drugs. We conclude that, at least in the isolated perfused rat pancreas, alpha 2-adrenergic receptors are involved in the inhibition of IRI release induced by catecholamines. On the contrary, the alpha-adrenergic system does not seem to play an essential role in the regulation of IRG secretion; the potentiation of the epinephrine-induced stimulation of A cell function by the alpha-adrenergic blockade could be accounted for by a greater availability of the catecholamine at the beta-receptor binding sites. PMID- 2880702 TI - Changes in glucagon do not play an essential role in the glucoregulatory responses to mild hyperinsulinemia in dogs. AB - To examine whether an increase in the glucagon concentration is essential for restoring hepatic glucose output following moderate decrements in blood glucose, we used isotope dilution techniques in trained conscious dogs (n = 5) to measure glucose production (Ra) and glucose utilization (Rd) during mild hyperinsulinemia (19 +/- 1 mU/l). In Study A, when insulin was infused to raise plasma insulin (IRI) from 13 +/- 2 to 19 +/- 1 mU/l, basal glucose (93 +/- 3 mg/dl) fell at a rate of 0.37 +/- 0.06 mg/dl/min over 30 min. Ra fell from 2.8 +/- 0.4 mg/kg/min by 0.5 +/- 0.1 mg/kg/min at 20 min (P less than 0.05), but recovered to baseline by 30 min; glucagon (IRG) fell transiently but returned to baseline by 45 min. In Study B, endogenous secretion of IRI and IRG was suppressed by infusion of somatostatin (0.2 microgram/kg/min), while peripheral concentrations were maintained constant by replacing glucagon (0.65 ng/kg/min) and insulin (0.225 mU/kg/min). Steady-state baseline plasma IRI, IRG, glucose and glucose turnover rates were similar to Study A; hyperinsulinemia was then induced as in Study A. Glucose fell by 0.78 +/- 0.19 mg/dl/min over 30 min and, as in Study A, Ra decreased transiently, but recovered to baseline by 30 min. The restoration of Ra occurred in study B despite constant IRG, and preceded later increments in cortisol and catecholamines at 60-90 min. Thus, in both studies A and B, Ra recovered to baseline without an increase in IRG and before the onset of significant hypoglycemia (glucose 83 +/- 1 and 70 +/- 1 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2880703 TI - [Selective blocking of parasympathetic ganglia]. PMID- 2880704 TI - [Comparison of famotidine and ranitidine in duodenal ulcer]. PMID- 2880705 TI - Rational use of analgesics in the treatment of the rheumatic disorders. AB - To the average arthritic patient, pain relief is usually his or her first priority in treatment. Thus, analgesics still have a part to play in the treatment of most arthritic conditions, even though the non-steroidal anti inflammatory drugs (NSAIDs) have the major therapeutic role in most cases. In the treatment of acute gout, the NSAIDs are the most important, and simple analgesics are relatively unimportant, but in the treatment of rheumatoid and osteoarthritis and other arthropathies, analgesics taken as and if required to cover the more painful periods of a day do have a role, usually in conjunction with NSAIDs and other agents. In general, the simple analgesics are better tolerated than the NSAIDs and less likely to produce gastrointestinal irritation. Although many clinicians consider that simple analgesics have little part to play in the treatment of rheumatoid arthritis and other inflammatory arthropathies, the patient often takes them without the physician's knowledge, in addition to the prescribed treatment. Some recently introduced analgesics bridge the gap between the simple analgesics and the more potent potentially addictive drugs such as pethidine and morphine, which are only indicated in extremely painful crises or after traumatic episodes and surgical operations. PMID- 2880706 TI - [Mucosal neuromas of the lips and tongue. Early symptoms of multiple endocrine neoplasia type IIb]. PMID- 2880707 TI - [Possibilities for influencing the antiedemic effect of glycerol and a glycerol and hydroxyethylrutoside combination by adrenergic antagonists in experimental brain edema]. PMID- 2880708 TI - [Effect of nutrition on small intestine gamma-glutamyltransferase in rats]. PMID- 2880709 TI - [Sensitivity of rat hepatocytes to phenobarbital after a single dose of N nitrosodiethylamine in the embryonal and postnatal period or after partial hepatectomy]. AB - For the hepatocarcinogenesis initiation one-fold N-nitrosodiethylamine (NDENA) action upon the livers of embryos and of the 4-weeks rats, before or after partial hepatectomy was used. Phenobarbital and repeated partial hepatectomies were used as the promotive factors. The promotion effect was evaluated by the quantity and size of hyperplastic liver nodules, where gamma glutamyltranspeptidase activity was revealed. It was determined, that NDENA affected rat liver cells in the embryonic period or at the age of 4 weeks after single partial hepatectomy proved to be more sensitive to the action of promoters. PMID- 2880710 TI - Benzodiazepines and memory. AB - Many anecdotal cases have been reported in the literature of dramatic memory impairment after benzodiazepine intake, raising psychobiological, pharmacological and forensic issues. This paper reviews some methodological difficulties encountered in human studies assessing memory function after benzodiazepine intake and the main results of these studies. Subjects studied are seldom insomniacs and the memory tests generally utilized are far from real-life situations. All benzodiazepines at some doses produce decrement in memory performance (anterograde amnesia) with a retrograde facilitation of retrieval, for the tasks learned before benzodiazepine intake. The mechanism of benzodiazepine induced amnesia is far from clear, but it has been shown that long term memory deficit could be the result of failure of memory consolidation due to rapid sleep onset (less than 5 minutes) after memory test performance during the night awakening (Roth et al. 1984). Many questions remain partially or totally unanswered: Is amnesia a specific effect of benzodiazepines? What are their other effects on cognitive functions? Which attitude to have towards a patient when the physician should prescribe a benzodiazepine? PMID- 2880711 TI - [History and pharmacology of trazodone]. AB - Trazodone, a non-tricyclic molecule, represents the first of a new generation of antidepressants. It is currently marketed in a number of European countries, in the United States and in Latin America. The pharmacological and biochemical data, the mechanism of action and the preferential indications of trazodone are presented and compared to those of imipramine and other tricyclics. Unlike imipramine, trazodone inhibits the adrenergic system. The two molecules have anti nociceptive properties, similar effects on the serotoninergic system and, after repeated administrations, they both reduce the density of beta-receptors. The clinical implications of the alpha-blocking activity of trazodone are reported. Trazodone is preferable to tricyclic anti-depressants in the treatment of depression in elderly subjects in general, and especially when they present closed angle glaucoma, prostatic hypertrophy, tremor or cardiovascular problems due to hyperactivity of the adrenergic system, as well as in organic depressions and in depression secondary to schizophrenia, alcoholism and in patients with Parkinson's disease. PMID- 2880712 TI - Carcinogenicity of by-products of disinfection in mouse and rat liver. AB - By-products of disinfection were tested for initiating and/or promoting activity in rat liver by using the rat liver foci bioassay. The assay uses an increased incidence of gamma-glutamyltranspeptidase-positive foci (GGT foci) as an indicator of carcinogenicity. The by-products of disinfection, including chloramine, halogenated humic acids, halogenated ethanes, halogenated acetonitriles, halogenated methanes, halogenated ethylenes, and N-Cl-piperidine, did not initiate GGT foci, which would indicate that they are not capable of initiating carcinogenesis. Chloroform and halogenated benzenes were tested in this assay for their ability to promote the occurrence of GGT foci and tumors initiated by diethylnitrosamine (DENA). Chloroform (1800 ppm in the drinking water) either had no effect or inhibited the occurrence of GGT foci when administered subsequent to a single dose of DENA. However, when the chloroform was administered in drinking water concurrently with weekly doses of DENA, it enhanced the formation of liver tumors. Of 20 halogenated benzenes tested, only 1,2,4,5-tetrachlorobenzene and hexachlorobenzene promoted the occurrence of DENA initiated GGT foci. Thus in rat liver, the tested by-products of drinking water disinfection did not demonstrate tumor-initiating activity, although a few appeared to possess tumor-promoting activity. Chloroform was also tested for tumor-promoting activity in 15-day-old Swiss mice initiated with ethylnitrosourea (ENU). At weaning they started to receive either 1800 ppm chloroform or 500 ppm sodium phenobarbital (the positive control for tumor promotion) in their drinking water. The mice continued to receive either chloroform or phenobarbital until 51 weeks of age and were sacrificed at 52 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2880713 TI - Trichloroacetic acid effects on rat liver peroxisomes and enzyme-altered foci. AB - The initiating and promoting effects of trichloroacetic acid (TCA) were investigated using a rat hepatic enzyme-altered foci bioassay. The experimental protocol used has been shown to induce gamma-glutamyltranspeptidase (GGT) positive foci in hepatic tissue following an initiating dose with a genotoxic carcinogen. Twenty-four hours following 2/3 partial hepatectomy, rats received either a single oral dose (1500 mg/kg) or 5000 ppm TCA in drinking water for 10, 20, or 30 days. Two weeks after the end of TCA exposure, the rats were promoted for 3 or 6 months with 500 ppm phenobarbital in drinking water. TCA failed to induce GGT-positive foci using this initiation protocol. In addition, groups of 2/3 partially hepatectomized rats were initiated with a single oral dose of diethylnitrosamine (10 mg/kg) and then administered 50, 500, or 5000 ppm TCA drinking water. In this promotion protocol, TCA exposure resulted in a significant increase in the number of GGT-positive foci. The ability of TCA to stimulate peroxisomal-dependent palmitoyl-coenzyme A oxidation was also investigated. Only the 5000 ppm TCA treatment within the promotion protocol resulted in a significant, although minor, stimulation of peroxisomal enzyme activity. The findings support the hypothesis that TCA may possess weak promoting activity in the rat liver. PMID- 2880715 TI - Taxol affects both the microtubular arrays of heliozoan axonemes and their microtubule-organizing center. AB - Short and long-term effects of the antitumor drug taxol on the microtubular axonemes and on the microtubule-organizing centroplast of the centrolhelidian Heterophrys marina have been investigated. Short-term treatment reveals that general aspects of cell structure remain substantially unaffected and that additional microtubule (MT) assembly in individual axonemes is accompanied by disassembly in others. However, the interaction between MTs, via cross-bridging associated proteins, is seriously affected as indicated by the numerous softly bent axopods with disturbed arrays of the normally hexagonal pattern. Stabilization of MTs becomes evident by the reexpansion of axopods during low temperature incubation and also by the rapid inhibition of the saltatory movement of the extrusive organelles. Rapidly reexpanding axonemes of cells incubated at higher temperatures and in high taxol concentrations arise asymmetrically from the microtubule-organizing centrosomal structure (centroplast) and form a single thick and thorn-like axopodium, indicating a certain disarrangement of the centrally located microtubule-organizing center (MTOC), which obviously is severely damaged after long-term treatment. With increasing disorganization of the centroplast's structure, these cells reveal themselves unable to sustain their regular microtubular axonemal cytoskeleton. Paradoxically, polymerization of free microtubules from the tubulin pool does not take place. Instead, paracrystalline arrays of twisted filaments appear within the cytoplasm. It is concluded that heliozoan MTs can only persist if stabilized by additional factors, such as permanent interaction with the intact centroplast, and that even in the presence of taxol, MTs unattached to such an MTOC will be intrinsically unstable. PMID- 2880714 TI - Anchoring of membrane proteins via phosphatidylinositol is deficient in two classes of Thy-1 negative mutant lymphoma cells. AB - Recent evidence shows that mature Thy-1 glycoprotein lacks amino acids 113-143 predicted from the cDNA sequence and is anchored to the plasma membrane by a phosphatidylinositol-containing glycolipid attached to amino acid 112. Previously characterized Thy-1-deficient mutant lymphoma lines of complementation classes A and E were analysed. They make detergent binding Thy-1 precursors but, in contrast to wild-type, the detergent binding moiety cannot be removed by phospholipase C. Moreover, tryptophan which only occurs at position 124 is incorporated into mutant but not parental Thy-1. This suggests that the mutants make a Thy-1 precursor of 143 amino acids but fail to replace its C-terminal end by a glycolipid anchor. PMID- 2880716 TI - Angina pectoris early after myocardial infarction: clinical experience of the multicentre post-infarction program. AB - In the Multicenter Post Infarction Program, 33% of 867 patients had early angina pectoris, i.e. angina between 2 days and hospital discharge 17 +/- 9 days after infarction. Early post-infarction angina was not significantly associated with cardiac death during 2.5 years of follow-up whereas both ventricular arrhythmias and left ventricular dysfunction were strongly and independently related to subsequent mortality. After myocardial infarction, there is no significant association between early angina pectoris and either ventricular arrhythmias or systolic or diastolic dysfunction of the left ventricle. However, patients with early post-infarction angina were one-and-a-half times as likely to be rehospitalized and two-and-a-half times as likely to experience recurrent non fatal myocardial infarction during the year after myocardial infarction. Exercise angina pectoris was associated with subsequent mortality but not with recurrent non-fatal myocardial infarction. ST segment depression greater than or equal to 1 mm or greater than or equal to 2 mm during exercise was not significantly associated with either subsequent death or non-fatal myocardial infarction. PMID- 2880717 TI - Beta-adrenoceptor blockade in the treatment of coronary heart disease. PMID- 2880718 TI - Tolerability and antiarrhythmic efficacy of disopyramide compared to lignocaine in selected patients with suspected acute myocardial infarction. AB - In a randomized open study with intravenous lignocaine and disopyramide in patients with suspected acute myocardial infarction and ventricular premature contractions the occurrence of cardiac events, adverse reactions, withdrawals and arrhythmias were compared. Of the total 68 patients included in the study, 33 were randomized to disopyramide and 35 to lignocaine treatment. The treatment was given for 24 hours or until withdrawal due to occurrence of serious cardiac events or side-effects possibly related to the drugs. Sustained ventricular tachycardia occurred in one patient in each treatment group. 15 per cent of the patients treated with disopyramide and 14 per cent of the patients treated with lignocaine were withdrawn because of adverse reactions. Withdrawals due to depressed left ventricular function and sinoatrial and atrioventricular conduction disturbances were not different in the two treatment groups. However, more patients treated with lignocaine had supraventricular arrhythmias compared to disopyramide. Significantly more patients treated with disopyramide obtained complete abolition of premature ventricular contractions on Holter recordings compared to lignocaine treatment (P less than 0.001). The results indicate that disopyramide and lignocaine can be used alternatively in the treatment of ventricular arrhythmias in patients with suspected acute myocardial infarction. PMID- 2880719 TI - Lack of clinically significant beta-blocking effect of propafenone. AB - To study possible beta-blocking effects of propafenone, a class 1c antiarrhythmic agent, electrocardiographic variables were studied at rest and during exercise. Forty-two patients with symptomatic ventricular arrhythmias were included. In 31 patients, exercise electrocardiograms before and after propafenone were available for study. The mean dose of propafenone was 603 mg for all 42 patients, 585 mg for patients undergoing exercise testing (range 450-1200). At rest, the PR interval, duration of P wave and QRS complex changed significantly without any change in the resting heart rate and QTc interval. During exercise there were no changes after propafenone in peak heart rate, PR interval, QTc interval, duration of exercise, or blood pressure. We conclude that, while class I effects are evident both at rest and after exercise, no clinically significant beta-blocking effects of propafenone could be demonstrated either at rest or during exercise. PMID- 2880720 TI - Testing with growth hormone-releasing factor (GRF(1-29)NH2) and somatomedin C measurements for the evaluation of growth hormone deficiency. AB - Growth hormone (GH) responses to GRF (1 microgram/kg BW i.v.) were investigated. Comparison between GRF(1-40) and GRF(1-29)NH2 in 11 young adult volunteers gave identical results. One hundred and thirty-one children and adolescents (45 with idiopathic GHD) were tested with GRF (1-29)NH2. The maximal GH levels (max GH) in response to GRF during the 120 min test period were found suitable to characterize the response. In cases without GHD no correlation to age, sex and pubertal development was observed. A maximal GH level of above 10 ng/ml was found to be normal. In 3 out of 86 children without GHD (one with Turner syndrome; two with simple obesity) max GH fell short of 10 ng/ml, while 11 of 45 cases with GHD exceeded this margin. In GHD, max GH was inversely correlated with age. There was no difference in max GH between groups with or without perinatal pathology as a presumed cause of GHD. GH levels to GRF were positively correlated with maximal GH level during sleep in GHD, but not correlated with responses seen to insulin or arginine. The value of GRF testing for the confirmation of GHD is discussed in the light of other GH stimulatory tests and basal somatomedin C measurements. It is suggested that the combination of testing with GRF and the determination of a basal SmC level offers a safe and convenient way to diagnose GHD in clinically suspected cases, though in some cases further diagnostic tests may be needed. PMID- 2880721 TI - Renal function in cystic fibrosis: proteinuria and enzymuria before and after tobramycin therapy. AB - Proteinuria and enzymuria were measured in 27 patients with Cystic Fibrosis before and after tobramycin therapy. Prior to treatment, kidney function was normal in 23 patients. Four patients showed a pathological proteinuria and two haematuria. Renal biopsy in one patient showed segmental basement membrane alterations on electron microscopy; there were no immunoglobulin deposits. During intravenous therapy with tobramycin (10 mg/kg per day) and azlocillin (100 mg/kg per day) mean urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion rose six fold and mean urinary alaninaminopeptidase excretion increased ten-fold. After cessation of therapy, enzymuria rapidly returned to pretreatment values in all 14 patients. Aerosol tobramycin therapy in four patients did not affect urinary excretion of NAG. It can be concluded that tobramycin did not cause persistent renal damage in our patients, whether given intravenously or as an aerosol. PMID- 2880722 TI - Beta-blocking effect and pharmacokinetics of pindolol in young and elderly hypertensive patients. AB - The pharmacokinetics and beta-blocking effect of pindolol has been compared in 20 patients with essential hypertension (WHO Stage I), 10 below 25 years of age and 10 older than 60 years. Each patient received pindolol 10 mg p.o. once a day for 5 days. The area under the curve (AUC) of pindolol was larger in the old than in the young patients both on the first (p less than 0.05) and the fifth (p less than 0.01) days. The AUC of pindolol was 14% higher on the fifth day compared to the first day in the elderly group, indicating minor accumulation at steady state. There was no change in AUC in the young patients. Endogenous creatinine clearance was lower in the old (80 +/- 9 ml/min) than in the young patients (150 +/- 45 ml/min). The beta-blocking effect did not differ between the groups at 2 h after administration of pindolol on Days 1 or 5. However, 24 h after the first and fifth doses approximately 60% of the beta-blockade persisted in the old group whereas 17 and 19% of the beta-blockade, respectively, persisted in the young group; the difference between the groups was statistically significant (p less than 0.01). The most probable explanation for the more sustained beta-blocking effect in the elderly is the physiologically decrease in renal function, which results in a more sustained plasma level of pindolol in those patients. PMID- 2880723 TI - Importance of oxidative polymorphism and levomepromazine treatment on the steady state blood concentrations of clomipramine and its major metabolites. AB - The relationship between the debrisoquine oxidation status and the metabolism of clomipramine was studied in nine healthy volunteers (five rapid hydroxylators, three slow hydroxylators and one of intermediate status). The hydroxylation of clomipramine and demethylclomipramine were found to covary with that of debrisoquine, whereas demethylation of clomipramine seemed to be independent of the debrisoquine hydroxylation phenotype. The steady-state blood concentrations of clomipramine and its three main metabolites were measured in 122 depressed patients. Thirteen patients who concomitantly received a neuroleptic tended to have higher levels of demethylclomipramine and clomipramine, whereas the levels of the hydroxylated metabolites were hardly affected. Benzodiazepine co administration did not modify the pharmacokinetics of clomipramine. The results suggest that benzodiazepines rather than levomepromazine should be used in depressed patients with anxiety and/or agitation in combination with the antidepressant treatment. PMID- 2880724 TI - T11TS, the cell surface molecule binding to the "erythrocyte receptor" of T lymphocytes: cellular distribution, purification to homogeneity and biochemical properties. AB - T11 target structure (T11TS) is a sheep cell surface glycoprotein that binds to the E receptor of human and sheep T lymphocytes. Here we report that T11TS has a broad tissue distribution, including mature and immature hematopoietic cells, vascular endothelium and smooth muscle. The density of T11TS expression was determined by Scatchard analysis with radiolabeled anti-T11TS monoclonal antibody. Red blood cells bound 10,000, and leukocytes bound 4000 to 23,000 antibody molecules per cell. T11TS was purified to homogeneity by immune-affinity and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and some of its biochemical properties were determined. T11TS is an acidic (pI 4.5) membrane glycoprotein that binds to concanavalin A. It has 2 or 3 N glycosidically linked carbohydrate side chains of the mature phenotype, no O linked sugars, and an apparent mol. mass of 42 kDa (glycosylated) and 32 kDa (deglycosylated). The anti-T11TS monoclonal antibody L180/1, which blocks binding of sheep red blood cells to CD2, recognizes a protein determinant on T11TS. These findings are discussed with respect to the possible function of the CD2-T11TS system as a set of complementary cell interaction molecules involved in T cell activation. PMID- 2880725 TI - Purification and N-terminal amino acid sequence of the human T lymphocyte CD2 (T11) surface antigen. AB - CD2 (the sheep erythrocyte receptor) is a surface antigen of human T lymphocytes. A role for CD2 in T cell function has been implicated from the observation that antibodies against CD2 are capable of transmitting both positive and negative signals for cell growth. Biochemically, the molecule has been identified as a broad band on sodium dodecyl sulfate (SDS)-polyacrylamide gels of about 50-58 kDa. This communication demonstrates that CD2 contains N-linked carbohydrate as endo-beta-N-acetylglucosaminidase F digestion reduced its apparent mol. mass to a compact band of 40 kDa. CD2 was purified from the T leukemia cell line J6 by immunoaffinity chromatography and preparative SDS-polyacrylamide gel electrophoresis (PAGE). Four bands of 52, 54, 56 and 58 kDa could be distinguished in the immunoaffinity-purified protein which formed a broad zone on SDS-PAGE extending from about 45 to 58 kDa. Preparative SDS-PAGE yielded a product suitable for determining the N-terminal amino acid sequence. Assignments were made for the first 26 (excluding the 23rd) residues and the sequence identified a novel polypeptide. PMID- 2880726 TI - Antiarrhythmic activity of flestolol, a novel ultra-short-acting beta adrenoceptor antagonist, in the dog. AB - The antiarrhythmic activity of flestolol, an ultra-short acting beta-adrenergic blocker lacking appreciable local anesthetic activity, was examined in several different canine ventricular arrhythmia models. Flestolol, at steady state infusions of 1-1,000 micrograms/kg per min, was generally ineffective in reversing either ouabain-induced or delayed ischemia-induced (24 h Harris dog) ventricular tachycardia. However, flestolol (1, 10 and 100 micrograms/kg per min) produced a dose-dependent decrease in l-norepinephrine (5 micrograms/kg i.v.) induced ventricular tachycardia in the 5-6 day old Harris dog; the effect of 100 micrograms/kg per min flestolol, 94% suppression of norepinephrine-induced ventricular tachycardia, was completely reversed 60 min after termination of flestolol infusion. In pentobarbital-anesthetized open-chest dogs with pretreatment heart rates greater than or equal to 145 beats/min, flestolol (10 micrograms/kg per min) reduced the incidence of ventricular fibrillation resulting from abrupt coronary artery occlusion compared to placebo-treated controls (15% or 2/13 vs. 70% or 7/10, respectively). These results demonstrate that flestolol has an antiarrhythmic profile consistent with its lack of local anesthetic activity and its ultra-short duration of beta-blockade. PMID- 2880727 TI - Characterization of adrenoceptor mechanisms in isolated guinea-pig uterine arteries. AB - The adrenoceptors of the guinea-pig uterine artery were characterized pharmacologically. Circular segments of the artery, approximately 2 mm long, and with an external diameter of 250 micron, were mounted in miniaturized tissue baths. Noradrenaline, methoxamine and phenylephrine (concentrations ranging from 10 nM to 1 mM), in the presence of propranolol (0.1 microM) and cocaine (1 microM), induced concentration-dependent contractions of the arterial segments. Clonidine (10 nM to 0.1 mM) was less effective in producing contraction of the vessel. Prazosin (10 nM to 1 microM) antagonized noradrenaline-induced contractions; its pA2 was 7.68. Rauwolscine (10 nM to 1 microM) had no effect on noradrenaline-induced contractions. Isoprenaline (10 nM to 0.1 mM) in the presence of prazosin (1 microM) and cocaine (1 microM) had no relaxant effect on arteries contracted submaximally by prostaglandin F2 alpha (5 microM). Cocaine or normetanephrine treatment did not influence the noradrenaline-induced contractions. It is concluded that in guinea-pig uterine arteries, amine-induced contractions are mediated predominantly by alpha 1-adrenoceptors and that in this arterial preparation, relaxant beta-adrenoceptor effects and neuronal or extraneuronal uptake are of minor if any importance. PMID- 2880729 TI - Somatostatin: an inhibitory parasympathetic transmitter in the human heart? PMID- 2880728 TI - Effects of blockade of alpha 1- and alpha 2-adrenoceptors on vasoconstrictor responses to single and twin pulse stimulation in rat tail artery. AB - Perfused/superfused proximal segments of Sprague-Dawley rat tail artery were stimulated at supramaximal voltage with two 1 ms square wave pulses. The pulse interval was either 10 or 20 s. With either interval the response to each pulse was similar, amounting to about 20 mm Hg increase in perfusion pressure. Prazosin (0.1 nM) approximately halved the response to both pulses whereas idazoxan (30 nM) was without effect. With an interval of 10 s, cocaine (4 microM) greatly increased the response to the first but not to the second pulse; in the presence of cocaine, prazosin (1 nM) again reduced both responses whereas idazoxan (30 nM) reduced the response to the first pulse but increased the response to the second. With an interval of 20 s, cocaine increased the responses to both pulses to a similar degree; in the presence of cocaine, idazoxan reduced the responses to both pulses. The results suggest that in rat tail artery, inhibition of the neuronal uptake process is required if noradrenaline released after stimulation with a single pulse is to reach smooth muscle alpha 2-adrenoceptors, and if feedback inhibition is to persist for more than 10 s. PMID- 2880730 TI - Intracerebroventricular morphine produces diuresis 24 h after previous dynorphin/morphine treatment. AB - The effect of dynorphin A-(1-13) on morphine-induced urine output was studied in the rat. The previous simultaneous intracerebroventricular (i.c.v.) injection of dynorphin (20 micrograms/rat) and morphine (20 micrograms/rat) altered the response of rat given morphine (20 micrograms/rat) 24 h later, producing a 3-fold increase in urine output. In contrast, previous injection of dynorphin or morphine alone had no effect. PMID- 2880732 TI - Comparative beta-blocking activities and electrophysiologic actions of racemic sotalol and its optical isomers in anesthetized dogs. AB - The relative activities of d-, 1- and racemic-sotalol were studied in two series of anesthetized dogs. Estimates of relative beta-adrenergic blocking potency were based upon the ability of the compounds to antagonize isoproterenol-elicited increases in heart rate and decreases in diastolic blood pressure. On a molar basis, d-sotalol displayed 1/12-1/14th and 1-sotalol 1.6-3.2 X the potency of the racemic parent drug as beta-antagonists. His bundle electrogram (HBE) measurements, surface ECG recordings and the extra stimulus technique at a constant pacing cycle length were utilized to assess the comparative effects of sotalol and its optical isomers on cardiac conduction and refractoriness. At i.v. doses spanning equiactive beta-blocking levels, d- (1, 4, 16 mg X kg-1), 1- (0.25, 1, 4 mg X kg-1) or dl-sotalol (0.5, 2, 8 mg X kg-1) caused dose-dependent increases in ventricular and, to an even greater extent, atrial refractoriness. The mean plasma drug concentrations (Cp) attained with these doses were: d sotalol 9.5, 44 and 267 nmol X l-1; 1-sotalol 9.6, 16 and 66 nmol X l-1; and dl sotalol 5.4, 23 and 106 nmol X l-1. The relative mg potency from greatest to least was 1-sotalol greater than dl-sotalol greater than d-sotalol in prolonging the ventricular effective refractory period (V-ERP); the mean increases above control at the highest dose of each were 58 +/- 4, 47 +/- 6 and 38 +/- 3 ms, respectively. At those same dose levels, atrial refractoriness (A-ERP) was maximally elevated 49 +/- 11, 82 +/- 5 and 104 +/- 10 ms by 1-, dl- and d sotalol, respectively. These increases in refractoriness occurred without alterations in atrial, His-Purkinje or ventricular conduction velocity; however, all three forms of sotalol significantly reduced AV nodal conduction. At the dose multiples studied, the effects on this variable (AH interval) were greatest following 1-sotalol (20-60 ms) or racemic sotalol (20-57 ms) and least following the d-isomer (7-43 ms). The profile of effects observed with d-sotalol is that of an agent with Class III electrophysiologic effects and weak beta-adrenergic blocking properties. PMID- 2880731 TI - Neurophysiological effects of buspirone and isapirone in the hippocampus: comparison with 5-hydroxytryptamine. AB - The neurophysiological effects of two novel anxiolytic compounds, buspirone and isapirone (TVX Q 7821), were compared with those of 5-hydroxytryptamine (5-HT) on the population spike in the CA1 region of the rat hippocampal slice. Micromolar concentrations of the two drugs mimicked the inhibitory effect of 5-HT but unlike 5-HT they did not produce any significant excitation. In slices in which 5-HT was purely excitatory, there was a marked reduction in the inhibitory response to these agents. The effect of isapirone was antagonised by spiperone. These results suggest that buspirone and isapirone are agonists for 5-HT1A receptors in the hippocampus. PMID- 2880733 TI - Prejunctional alpha 2-adrenoceptors modulate stimulation-evoked norepinephrine release in rabbit lateral saphenous vein. AB - Segments of rabbit lateral saphenous vein prelabelled with [3H]noradrenaline were perfused and superfused with physiological salt solution. Tritium overflow evoked by transmural nerve stimulation (3 Hz for 2 min) was abolished by tetrodotoxin (1 microM). The selective alpha 2-adrenoceptor agonist UK 14,304 inhibited stimulation-evoked 3H-overflow in a concentration-dependent manner, with an IC50 of 71 nM. In contrast, the alpha 2-adrenoceptor agonist B-HT 933 had no effect on 3H-overflow in concentrations up to 10 microM. The selective alpha 2-adrenoceptor antagonists idazoxan and SKF 86466, as well as the non-selective alpha-antagonist phentolamine, facilitated the nerve stimulation evoked 3H-overflow, with an order of potency of idazoxan greater than or equal to phentolamine greater than SK&F 86466. Prazosin (100 nM) had little effect on 3H-overflow. These findings suggest that stimulation-evoked neurotransmitter release is modulated via prejunctional alpha 2-adrenoceptors. PMID- 2880734 TI - Anxiolytic action of CGS 9896 on mouse exploratory behavior. AB - A new non-benzodiazepine compound proposed as a non-sedating anxiolytic was tested in the mouse exploratory model of anxiety. CGS 9896 significantly increased the number of light dark transitions at doses beginning at 7.5 mg/kg i.p. Analysis of general locomotor activity at these doses revealed no change in spontaneous motor activity in a photocell equipped activity monitor. Pretreatment with the benzodiazepine receptor antagonist, Ro15-1788, 10 mg/kg i.p., blocked the increase in light dark transitions produced by CGS 9896. These data support the interpretation that CGS 9896 acts as an anxiolytic through the benzodiazepine receptor, and appears to have no sedating properties within the anxiolytic dose range. PMID- 2880735 TI - Effects of the enantiomers of MDA, MDMA and related analogues on [3H]serotonin and [3H]dopamine release from superfused rat brain slices. AB - The primary amines 3,4-methylenedioxyamphetamine (MDA), and 1-(1,3-benzodioxol-5 yl)-2-butanamine (BDB) were measured for efficacy in release of [3H]serotonin (5 HT) from rat hippocampal slices, and release of [3H]dopamine (DA) from rat caudate nucleus slices. The N-methyl derivatives of MDA and BDB, MDMA and MBDB, respectively, and the optical antipodes of these four agents were compared in this paradigm. All of the test compounds demonstrated a similar efficacy of [3H]5 HT release in the micromolar concentration range. No significant stereoselectivity was seen in measurements of 5-HT release. However, striking differences were found between the test compounds when [3H]DA release was studied. N-methylation of racemic MDA resulted in a decreased ability to release DA, while side chain extension from alpha-methyl to alpha-ethyl completely abolished this activity. Stereoselectivity for the S-(+)-isomers of MDA and MDMA was also demonstrated in the DA release studies. Correlation of these biochemical findings with human subjective reports indicates that serotonin release may play a more important role in the mechanism of action than does dopamine release. PMID- 2880736 TI - Antidepressant administration has a differential effect on rat brain alpha 2 adrenoceptor sensitivity to agonists and antagonists. AB - The aim of this study was to characterize the action of antidepressants on rat brain alpha 2-adrenoceptor function by examining their effect on the yohimbine sensitive component of the cAMP response to adrenoceptor agonists. Using a prelabeling technique for measuring cAMP accumulation, it was found that chronic (2 weeks) administration of antidepressants increased the potency of yohimbine, an alpha 2-adrenoceptor antagonist, to inhibit norepinephrine-stimulated cAMP accumulation in rat brain cerebral cortical slices. In contrast, antidepressant treatment decreased the ability of the alpha-adrenoceptor agonist 6 fluoronorepinephrine to augment isoproterenol-stimulated cAMP accumulation. The results suggest that antidepressants alter rat brain alpha 2-adrenergic function by shifting the receptor to antagonist-preferring state. Such an effect may contribute to the change in noradrenoceptor responsiveness that is characteristic of antidepressant administration. PMID- 2880737 TI - Effects of 5-HT1A selective anxiolytics on lordosis behavior: interactions with progesterone. AB - Ipsapirone and gepirone, but not buspirone, facilitated lordosis in estrogen treated rats, whereas all three drugs inhibited this behavior in rats treated with estrogen and progesterone. When administered at higher doses, ipsapirone, gepirone and buspirone inhibited lordosis in rats treated with either estrogen or estrogen and progesterone. These data are consistent with the proposal that 5 HT1A receptors mediate lordosis-inhibiting effects of 5-HT, and further suggest that some 5-HT1A agonists may facilitate lordosis by activity at autoreceptors. Finally, these data show that progesterone may modulate activity at 5-HT1A receptors. PMID- 2880738 TI - Modulation of agonist and antagonist interactions at kidney alpha 1-adrenoceptors by nucleotides and metal ions. AB - In order to characterize putative high- and low-affinity states of the renal alpha 1-adrenoceptor, binding sites for the selective antagonist radioligand [3H]prazosin were examined in washed membranes prepared from rat renal cortex and medulla. Norepinephrine competition curves at [3H]prazosin sites were biphasic and were best fit by a two-site model. Na+ and GTP selectively decreased the proportion of sites exhibiting a high affinity for norepinephrine. In contrast, Mg2+ facilitated high-affinity interactions of norepinephrine at the renal alpha 1-receptor. Guanine nucleotides and Na+ increased the affinity of some antagonists [( 3H]prazosin, WB-4101), but not others (phentolamine). Mg2+ again had opposite effects. The effects of ions and nucleotides on both agonist and antagonist interactions were concentration-dependent. The order of potencies for monovalent cations (Na+ greater than Li+ much greater than K+), divalent cations (Mn2+ greater than Mg2+) and nucleotides (Gpp (NH)p, GTP much greater than GMP, ATP) were similar to those reported for cyclase-coupled receptor systems. However, unlike other divalent cations Ca2+ decreased both agonist and antagonist binding, possibly due to a Ca2+-sensitive proteinase. Receptor binding properties were similar in renal cortex and medulla. Renal alpha 1-receptor sites appear to display high- and low-affinity states with respect to agonists, and the equilibrium between these states may be modulated by guanine nucleotides and mono and divalent metal ions. Some antagonists appear to bind preferentially to sites with low agonist affinity, and this effect is probably independent of retained endogenous catecholamines. PMID- 2880739 TI - Changes in membrane potential and phosphoinositides during alpha 1-adrenoceptor stimulation in smooth muscle cells of guinea-pig taenia caeci. AB - The effect of a submaximal concentration of adrenaline (3-5 microM) was studied in taenia caeci smooth muscle cells. Membrane potential hyperpolarization was observed in intact muscle preparations and this response could be separated into two phases, depending on the state of a membrane-bound calcium compartment. The effect of alpha 1-adrenergic stimulation was also measured by [3H]inositol incorporation into phospholipid and inositol phosphate fractions of taenia cell suspensions both in the absence and presence of 2.5 mM extracellular calcium. In the absence of extracellular calcium the inositol phospholipids increased within 15 s after stimulation, followed by enhanced inositol phosphates. With calcium present there was a biphasic increase in the phosphatidylinositol 4,5 bisphosphate (PIP2) fraction with a simultaneous release of inositol phosphates. Lithium ions affected the incorporation of label into the lipids but not into the inositol phosphate fractions. These findings suggest that, in taenia caeci cells, alpha 1-adrenergic-induced membrane hyperpolarization resulting in muscle relaxation is associated with changes in the PIP2 content. PMID- 2880740 TI - Ketanserin blocks alpha 1-adrenoceptors of porcine vascular smooth muscle cells. AB - The effect of ketanserin on alpha-adrenoceptors was studied in membrane preparations of the porcine aorta using [3H]prazosin and [3H]yohimbine binding assays to identify alpha 1- and alpha 2-adrenoceptors. Ketanserin bound to alpha adrenoceptors and the Ki value of ketanserin for alpha 1-adrenoceptors was 8.3 nM, a value practically equal to that of phentolamine (Ki = 7.2 nM). The Ki value of ketanserin for alpha 2-adrenoceptors was 3.3 microM. Thus, at the doses prescribed clinically, ketanserin blocks alpha 1- but not alpha 2-adrenoceptors of porcine vascular smooth muscle. PMID- 2880741 TI - Different toxicity of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) on the nigrostriatal and mesolimbic pathways. AB - The influence of MPTP (30 mg/kg X 2) on dopamine content and tyrosine hydroxylase activity in striatal, limbic and cortical areas of C-57/B16 mice was studied. General dopamine depletion was observed 24 h after the treatment, but 30 days after administration recovery was complete in all but the striatum. At 24 h, tyrosine hydroxylase activity was decreased only in striatum. It is proposed that MPTP acts differently in striatum and in other dopaminergic areas. PMID- 2880742 TI - Serum constituents and liver photomicrographs of wild Suncus murinus in the south of Taiwan. AB - Serum constituents and liver of the wild male suncus as well as of those bred and fed in our laboratory were examined serologically and histologically. The following results were obtained: The serum glutamic-oxaloacetic transaminase, gamma-glutamyl transaminase, inorganic phosphate, blood urea nitrogen, creatinine, uric acid, and zinc turbidity test levels of wild suncus were higher than those of 4 and 8 week old fed suncus. The total cholesterol level of wild suncus was lower than those of 4 and 8 week old fed suncus. In wild suncus, the total bilirubin and direct bilirubin levels were higher, and the Ca and albumin levels were lower than those of 4 week old fed suncus. However, no significant differences were observed between the wild and the 8 week old fed suncus. Although the alkaline phosphatese and thymol turbidity test levels of wild suncus were larger than those of 8 week old fed suncus, no significant differences were observed between the wild and the 4 week old fed suncus. The histological study revealed the presence of fatty droplets in only 2 of the 67 wild suncus examined while fatty droplets (grade +) were observed in almost all the fed suncus. In one case of the wild suncus, moderate round cell infiltration in interlobular connective tissue was found. PMID- 2880743 TI - The effect of lysine acetylsalicylate on somatostatin inhibition of insulin secretion induced by arginine. AB - The inhibitory effect of somatostatin (SRIF) on immunoreactive insulin release and on many other hormonal secretions has been widely studied in both animal and man. However, the mechanism by which SRIF acts on these functions remains poorly defined. Aim of this study is to determine the inhibitory effect of SRIF on insulin secretion induced by arginine after the administration of lysine acetylsalicylate (LAS) in a dose which inhibits the endogenous synthesis of prostaglandins. Ten healthy informed volunteer subjects were studied. Four studies were carried out in randomized order, each one separated by a three day interval. The first study was a test of arginine (25 g i.v. in 30 min). The second study was a test of arginine with SRIF infusion (150 micrograms bolus followed by 100 micrograms/h for 120 min). The third study was a test of arginine with an infusion of SRIF and LAS (66 mg/min for 120 min). The fourth study was a test of arginine with LAS infusion. Plasma insulin levels were determined by radioimmunoassay. After arginine administration the typical biphasic insulin response was observed with a precocious peak at 3 min and a late peak at 30 min. This response is not significantly modified under LAS infusion. With the infusion of SRIF at a dose of 100 micrograms/hr after arginine administration only a very modest insulin response was observed. The addition of LAS does not modify the inhibitory effect of SRIF on insulin secretion induced by arginine. This result demonstrates that the inhibitory action of SRIF on the secretion of insulin is not dependent upon the activation of the endocellular prostaglandin system. PMID- 2880744 TI - Effects of neuroleptics administered to lactating rats on the behavioral development of offspring. AB - Effects of diazepam (DZP) and haloperidol (HAL) given to nursing mothers from the day after delivery to weaning on the behavioral development of their pups were investigated. Weight gain in the pups of mothers that received these drugs did not differ from that in the control pups. Male and female pups exposed to HAL through the milk showed an increase of aggressive behavior (attacking and pinning play) when examined within the social unit of the colony at 4 weeks of age. Although an age-related decrease in this play was observed in the pups of all groups at 7 weeks of age, HAL exposed male and female pups or DZP exposed female pups showed this play more frequently than control pups. At 5 weeks of age, male and female pups exposed to DZP or HAL showed an increase in central ambulation of open-field, in spite of no change in total ambulation. Female pups exposed to DZP or HAL showed an increase of rearing. Female pups exposed to DZP or HAL took more time to reach the goal and made more errors in the maze test at 13-15 weeks of age. Male pups exposed to DZP or HAL showed a decrease in the number of complete mounts. Female pups exposed to DZP or HAL showed a decrease in the number of complete lordoses and an increase in the number of defensive behavior. These results indicate that neuroleptics administered to the dams appear to modify the functioning development of the brain in their offspring. PMID- 2880745 TI - Bovine lens neutral proteinase preferentially hydrolyses oxidatively modified glutamine synthetase. PMID- 2880746 TI - Bulk enrichment of transplantable hemopoietic stem cell subsets from lipopolysaccharide-stimulated murine spleen. AB - Counterflow centrifugal elutriation (CCE) in combination with density flotation centrifugation and fluorescence-activated cell sorting on wheat-germ agglutinin FITC(WGA)-binding cells within the light-scatter "blast window" were used consecutively to enrich pluripotent hemopoietic stem cells (HSC) in bulk from lipopolysaccharide-stimulated mouse spleen. The medium-to-strong WGA + ve fraction contained 3.10(6) cells isolated from 3-4 X 10(9) spleen cells, with an average of 126% day-12 CFU-S and 65% day-8 CFU-S as calculated on the basis of their seeding fraction, suggesting that virtually all cells represented in vivo macroscopic colony formers. In view of the large differences reported elsewhere between stem cell subsets differing in reconstitutive capacity and secondary stem cell generation ability, we also studied various isolated cell fractions with respect to spleen colony formation, radioprotective ability, and spleen- and marrow- repopulating ability. Day-8 and day-12 CFU-S copurified when isolated by CCE. Cells from a fraction with high affinity for WGA were most highly enriched for their radioprotective ability (RPA) and their ability to repopulate the cellularity of the spleen and femur of irradiated recipients. This fraction contained virtually pure day-12 CFU-S. However, the ability to generate secondary day-12 CFU-S and CFU-GM in irradiated organs was enriched most in the medium WGA + ve cell fraction. MRA and SRA, according to the latter criteria, could therefore be partly separated from day-12 CFU-S and RPA on the basis of affinity for WGA. The data strongly suggest that at least part of all day-12 CFU-S have a high potential to proliferate and differentiate into mature progeny, but a relatively low self-renewal ability, and may therefore not be representative of the genuine stem cell. PMID- 2880747 TI - Theophylline in maintenance treatment of chronic asthma: concentration-dependent additional effect to beta 2-agonist therapy. AB - The effect of long-term treatment with theophylline was studied in 20 chronic asthmatic patients receiving oral and inhaled beta 2-agonists. In a double-blind, randomized cross-over fashion during three consecutive 6-week periods, the patients received theophylline in individually adjusted dosages or placebo to obtain plasma concentrations of 25-45 mumol/l, 50-85 mumol/l and 0, respectively. PEF, beta 2-aerosol consumption, symptom scores and side-effects were recorded daily. The addition of theophylline caused a significant further bronchodilating effect. There was, however, a large interindividual variation in response to additional theophylline and only half of the subjects were responders. Those responding had increased therapeutic efficacy from a steady-state concentration in the range of 50-85 mumol/l compared to the lower concentration. The responders had, on average, more pronounced air-flow obstruction. The incidence of adverse reactions increased with increasing concentrations of theophylline. PMID- 2880749 TI - [Complex approach to evaluating the antipsychotic properties of neuroleptics modeled on fenamine sterotypy in cats]. AB - It was shown that the ability of neuroleptics to cause the high-amplitude wave bursts in sensorimotor cortex in cats with phenamine stereotypy may indicate antipsychotic properties of the drugs whereas suppression of motor automatism largely testifies to their extrapyramidal effects. PMID- 2880748 TI - Influence of substratum on the retrograde response of the rat superior cervical ganglion in vitro. AB - To study the role of the substratum on the retrograde response of injured peripheral noradrenergic neurons, embryonic rat superior cervical ganglia were grown in vitro on four different substrata: collagen, poly-D-lysine, fibronectin, or tissue culture plastic. The rate and pattern of neurite outgrowth were determined for a 2-week period following injury with explantation. In addition, changes in the activity of tyrosine hydroxylase, the neurotransmitter enzyme that has been shown to be altered during the retrograde response, was measured. The pattern and rate of neurite outgrowth varied directly with the ability of the neuronal growth cone to adhere to the underlying substratum. On poly-D-lysine and collagen, neurites grew as individual processes with extensive branching, whereas on plastic and fibronectin there was little branching and marked neurite fasciculation. The rate of neurite elongation on poly-D-lysine (0.75 mm/day) was faster than on collagen (.53 mm/day), fibronectin (0.33 mm/day), or plastic (0.15 mm/day). On plastic, neurons of the superior cervical ganglion showed a severe and prolonged retrograde response as characterized by a reversible decrease in tyrosine hydroxylase activity to 28% of control which persisted until the 10th day in culture. In contrast, on collagen, there was a smaller, but still significant, decrease in tyrosine hydroxylase activity to 73% of control which lasted only 5 to 6 days. On poly-D-lysine, there was no measureable change in the activity of that enzyme after injury. These studies provide quantitative evidence showing an important role of the microenvironment, and in particular the extracellular matrix, in determining the ability of neurons to respond successfully to injury. PMID- 2880750 TI - [Prediction of the parameters of the accumulation of 1,4-benzodiazepine derivatives in the body of mice based on their excretory kinetics]. AB - Kinetics of 14C-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepin-2-one (I) excretion from the mouse body following a single and long-term administration of the compound was studied. It was shown that kinetics of excretion of total radioactive material in the urine and feces is a sum of monoexponential processes. Prediction of the compound accumulation in the mouse body during its long-term administration was performed. Parameters of accumulation of the compound, diazepam, chlordiazepoxide and phenazepam were compared. Significant, reciprocally compensated changes in relative efficacy and the rate of excretion of total radioactivity in the urine and feces during a long-term administration were noted. It is recommended to take into consideration the events studied at a chronic administration of derivatives of 1,4-benzodiazepine. PMID- 2880751 TI - Pi in equilibrium ATP exchange in the absence of proton gradient by the H+-ATPase from yeast plasma membranes. AB - Purified soluble H+-ATPase from Schizosaccharomyces pombe catalyzes a Pi in equilibrium ATP exchange in the absence of a H+ gradient. When the pH of the assay medium is raised from 5.5 to 8.0 there is a decrease of the ATPase activity and an increase of the rate of Pi in equilibrium ATP exchange. At pH 7.0 the addition of the organic solvent dimethyl sulfoxide (20%, v/v) promotes a decrease of ATPase activity and an increase of the Pi in equilibrium ATP exchange reaction. The effect of the organic solvent on the Pi in equilibrium ATP exchange is related to a decrease of the apparent Km for Pi. PMID- 2880752 TI - [Participation of neuromediators in neuronal mechanisms of attention and perception of visual information in food-getting behavior]. AB - A directed visual attention of the cat towards the site of reinforcement entailed an increase of the firing rate of the visual cortex' neurons. Neurotransmitters applied microiontophoretically altered the firing rate within time intervals corresponding to the level of visual attention and perception of visual stimulus. PMID- 2880753 TI - [Effects of various pancreatic secretagogues on somatostatin binding to rat pancreatic acinar cell plasma membranes]. AB - The effects of pretreatment with pancreatic secretagogues and subsequently activated cellular events on [125I-Tyr1] somatostatin binding to acinar membranes were studied. Pretreatment of pancreatic acini with bombesin at increasing concentrations for 120 min reduced labeled somatostatin binding to the acinar membranes in a dose-dependent fashion with a maximal reduction of binding at 10( 8)M bombesin (44.3 +/- 1.8% of control). The maximal inhibition of labeled somatostatin binding by pretreatment with bombesin was almost comparable to that with COOH-terminal octapeptide cholecystokinin (CCK8) or carbamylcholine (carbachol). Furthermore, pretreatment of acini with vasoactive intestinal peptide (VIP) as well as secretin resulted in a small, but significant decrease of subsequent labeled somatostatin binding. In addition, adenosine 3', 5' cyclic nucleotide derivatives or a phosphodiesterase inhibitor mimicked the effect of VIP or secretin. The effect of simultaneous pretreatment of acini with VIP and carbachol on subsequent labeled somatostatin binding appeared to be almost equal to the calculated additive value for each peptide. These results suggest that the binding of somatostatin to its receptors in the pancreatic acini may be regulated via two functionally distinct pathways. PMID- 2880754 TI - Atypical lichen planus associated with ulcerative colitis. AB - A case is reported of a patient known to have ulcerative colitis who developed atypical lichen planus. This did not resolve when the patient discontinued sulphasalazine treatment but became more extensive within 48 h of an exacerbation of colitis. This case supports the view that there may be an association between ulcerative colitis and lichen planus. PMID- 2880756 TI - Advanced abdominal pregnancy in Muhimbili Medical Centre, Tanzania. AB - A prospective study was conducted at Muhimbili Medical Centre (MMC) over a 2-year period on 16 patients with advanced abdominocyesis. The incidence of 1 in 3259 deliveries was higher than that of previous years. Infertility prior to index pregnancy was a significant antecedent factor (P less than 0.001). The most consistent symptom both in early and late pregnancy was abdominal pain. Difficulty in fetal palpation and abnormal lies were the most significant signs. The sensitivity of clinical suspicion was 68%, ultrasound 85% and X-ray diagnosis 93%. Sepsis was the leading maternal complication, especially when the placenta was left in situ. Perinatal mortality was 87.5% and maternal mortality was 6.4%. Abdominal pregnancy remains a diagnostic challenge and certain aspects of fetal mortality are ill-understood. Early diagnosis of abdominal pregnancy can be improved upon by more detailed history taking, a high index of suspicion and meticulous interpretation of sonographic and radiological signs. It is suggested that the placenta be removed except in the rarest trying cases and that pregnancy be terminated on diagnosis. PMID- 2880755 TI - Prevention of postoperative infection in cesarean section after rupture of the membranes. AB - Patients having a cesarean section more than 6 h after rupture of the membranes constitute a high risk group for postoperative infections. Two such groups were studied. Patients were given either cefuroxime 1.5 g every 8th hour for 24 h followed by cefadroxil 0.5 g twice daily for 6 days or received no medication. The infection rate was significantly reduced in the treatment group as compared to the control group (15% vs. 48%). Non-infected patients had a significantly shorter stay in hospital (8 days vs. 12 days). Combined use of these drugs for prevention of post-cesarean infection has not previously been reported. No side effects of the antibiotic prophylaxis were reported. PMID- 2880757 TI - Reproductive performance after eclampsia. AB - Eclampsia is a common complication of pregnancy in Ibadan, although its long term effects on subsequent pregnancies is unknown. In a prospective study of 64 women who had eclampsia in their previous pregnancies and were followed up in their current pregnancies, 15.6% of them had recurrent eclampsia, in spite of optimal antenatal care. Of the 18 patients with diastolic blood pressure of 80 mmHg 22.2% or over at booking had antepartum or intrapartum eclampsia as compared with only 2.2% of 46 patients with diastolic blood pressure of less than 80 mmHg at booking. This finding was statistically significant (P less than 0.01), showing that the diastolic blood pressure at booking can be a measure of the potential for developing eclampsia because of the possibility of residual hypertension on which pre-eclampsia may be superimposed. Similarly, there was a significant association (P less than 0.05) between the birthweight of the babies and the diastolic blood pressure at booking, and may be a measure of the effect of vascular effect of pre-eclampsia on the placenta. However, there was no difference in the perinatal mortality rate in this study and the overall hospital figures in spite of the high risk pregnancies being managed. It was concluded, therefore, that the outcome of these pregnancies would depend much on the standard of antenatal care provided for the patients. PMID- 2880758 TI - Determination of trace and bulk elements in plasma and erythrocytes of healthy pregnant women by PIXE method. AB - Particle Induced X-ray Emission (PIXE) analysis of blood samples from healthy pregnant women was carried out. Elements S, Ca, P, K, Cl, Fe, Zn, Cu, Rb and Br were detected, in red blood cells while S, Ca, P. K, Cl, Fe, Zn, Cu, Ni, Br in the plasma. The concentrations of Ca, K and Br were found to be stable throughout pregnancy, others exhibited significant alterations. The importance of macro- and microelement metabolisms during pregnancy and their role in the intrauterine development is summarized. PMID- 2880759 TI - Determination of trace and bulk elements in plasma and erythrocytes of diabetic pregnant women by PIXE method. AB - Proton-Induced X-Ray Emission (PIXE) analysis of blood samples from diabetic pregnant women was carried out. Elements S, Ca, P, K, Cl, Fe, Zn, Cu, Rb and Br were detected in red blood cells, while S, Ca, P, K, Cl, Fe, Zn, Cu, Ni, Br in the plasma. The concentrations of P, S, Ni, Cu were found to be higher, while those of K, Fe, and Zn were lower in diabetic plasma than in controls. Significantly higher concentrations were measured for P, S, Cl, Fe, Zn and Rb in diabetic erythrocytes compared to normals. Statistical evaluation of the results also indicated significant alteration in the changes of concentrations throughout the pregnancy. Diabetes also resulted in changes in most of the correlations observed in normal pregnancy between the concentrations of elements. PMID- 2880760 TI - Rapid regression through bromocriptine therapy of a suprasellar extending prolactinoma during pregnancy. AB - A 29-year-old woman is described who presented with amenorrhea and galactorrhea with a large prolactinoma which regressed on bromocriptine therapy. Treatment with bromocriptine was stopped when pregnancy was diagnosed but 6 weeks later the prolactinoma had regrown with suprasellar extension and lateral invasion of the cavernous sinus. When treatment with bromocriptine was reinstituted symptoms subsided within 24 h and serum prolactin concentrations fell from 54,000 mM/l to 2800 mU/l within 5 days and 500 mU/l 2 days after that. Pregnancy proceeded without complications and she entered spontaneous labor at term and delivered a healthy baby. One year after delivery, on treatment with bromocriptine, her serum prolactin concentration remains within the normal range and the CT scan shows persistence of a small prolactinoma, confined to the pituitary fossa. Bromocriptine should be the primary treatment for prolactinomas regardless of tumor size and may be safely stopped when pregnancy is desired. If pituitary tumor complications occur during pregnancy, reintroduction of treatment with bromocriptine should again be the treatment of choice. PMID- 2880761 TI - Time to conception after IUD removal: importance of duration of use, IUD type, pelvic inflammatory disease and age. AB - Some investigations of IUD use have demonstrated impaired ability to become pregnant after removal, while others have not. None of these studies, however, have adequately considered such potentially influencing variables as age and a history of pelvic inflammatory disease (PID). To study the effect of length of IUD use, IUD type and the modifying influences of age and PID history on time required to conceive, we followed women trying to become pregnant after removal of their IUD. Five hundred forty women in Ljubljana, Yugoslavia who were first fitted with an IUD between 1964 and 1972 and had their IUD removed in order to become pregnant were followed through 1980. We found no relationship between the duration of IUD use or type of IUD used, but increasing age and a history of PID each decreased the monthly probability of conception. These findings, along with other recent work, indicate that IUDs are a safe and efficacious contraceptive for women at low risk for sexually transmitted diseases. PMID- 2880762 TI - Hospital deaths in a high risk obstetric population: Karawa, Zaire. AB - Three thousand four hundred thirteen consecutive deliveries at a rural hospital in Zaire are examined. 85% of patients had goiters and 5% were cretins. Twenty maternal deaths occurred, or 5.9 per 1000 deliveries. Risk factors for maternal death included late presentation, advanced age (greater than or equal to 35 years), no education and presence of goiter or cretinism. Ninety percent of women who died were in critical condition at admission, 45% had labored greater than or equal to 48 h and 70% had uterine rupture. PMID- 2880763 TI - Twin birth weight discordancy in Nigeria. AB - The perinatal outcomes for 56 birth-weight discordant twin pairs among 622 total twin deliveries that occurred over an 18-month period at the University of Ilorin Teaching Hospital are analyzed. The incidence of twin birth-size discordancy was 9%. Mean birth-weight (kg) was 2.78 +/- 0.5 for the heavier twin and 1.90 +/- 0.5 for the smaller twin, with a mean intra-pair birth-weight difference of 0.88 kg (31.7% of the heavier twin). Perinatal mortality in the smaller infants was increased above the mean for all twin births. There were no perinatal deaths among the heavier infants. Discordant twinning was associated with high parity and a disproportionate increase of unlike-sex pairs. These observations suggest the preponderance of discordancy in dizygotic twinning. Increased awareness and surveillance for discrepant twin pairs are suggested in order to improve perinatal outcome. PMID- 2880764 TI - Ovarian function immediately after the menarche. AB - Estrone and pregnanediol-glucuronide values of early morning urine samples collected from young girls in the perimenarche were determined by radioimmunological technique. A total of 58 teenage girls started collecting urine samples after their menarche at various times. Of these, 9 completed collection within 100 days of the onset of the first menstrual period. In 3 cases, insignificant changes in estrone and pregnanediol levels were noted. Normal estrone values were found in 3 cases together with pregnanediol levels suggestive of ovulation. In 2 further cases the possibility of ovulation without follicular release was suggested. The results indicate that ovarian activity is unpredictable immediately following the menarche. Between very low levels of sexual steroid hormone production and those normally observed in adult females, all transitional values could be found. PMID- 2880765 TI - Surgical emergencies of the uterine adnexae during pregnancy. AB - During the 5-year period 1976-1980, seven cases of emergent surgical disease of the adnexae during pregnancy were encountered. The incidence of 1:1832 deliveries approximated that of appendicitis (1:1603 deliveries) during the same period. There were three cases of adnexal torsion, two ruptured ovarian cysts with hemorrhage, one heterotopic pregnancy, and one ruptured endometrioma. The right side was more commonly the site of the pathology, and abdominal pain the only consistent presenting symptom. Fever, tachycardia, and leukocytosis were inconsistent findings. Culdocentesis was positive in two cases. Four desired pregnancies were carried successfully to term postoperatively. Surgical emergencies of the adnexae will be encountered during pregnancy more commonly than is generally recognized. Aspects of obstetric management are described. If prompt surgical intervention is undertaken in pregnancy when the clinical picture suggests an acute abdomen, a satisfactory outcome can be expected. PMID- 2880766 TI - Selective screening for cancer of the cervix uteri in South Indian women. AB - In India, the need exists for a scheme of selective screening for women at high risk of developing cervical carcinoma. In this study, the incidence of abnormal cervical cytology amongst 500 pregnant south Indian women (gravida 3, para 2 or more) who were booked under the Post Partum Programme of the Government of India was compared to that of 200 primi and second gravidas from the same out patient clinic population. Abnormal cytology was detected in 3.6% of the women in the study group which was significantly higher (P less than 0.05) than that in the control (0.5%), indicating that the former are at higher risk of developing cervical cancer. Within the study group, abnormal cytology was not found to correlate with increasing age and gravidity or with any clinical parameter. The study and follow up could be carried out using existing facilities and manpower. Using existing personnel involved in the Post Partum Programme, a follow up rate of 67% could be achieved from among women with abnormal cervical cytology. The cost-effectiveness of this scheme of selective screening is borne out by the extremely modest additional cost incurred. PMID- 2880767 TI - Comparison of preventive use of metronidazole and ampicillin in women with a history of pelvic inflammatory disease undergoing first-trimester abortion. AB - In a double-blind controlled trial the efficacy of prophylactic metronidazole and pivampicillin to women with a history of pelvic inflammatory disease (PID) undergoing first-trimester abortion was assessed. Thirty-eight women received pivampicillin tablets 350 mg and 43 women metronidazole tablets 400 mg, given 1 h before and 4 and 8 h after the abortion. In the pivampicillin group 5 women (13.1%) and in the metronidazole group 8 women (18.6%) developed post-abortal PID, a non-significant difference (P greater than 0.05). The number of hospital days and amounts of antibiotics were not significantly different in the two treatment groups (all P-values greater than 0.05). Women with a history of PID were found to be at risk of contracting postabortal PID. PMID- 2880768 TI - Poor prognostic value of the basal fetal heart rate as observed during antenatal monitoring. AB - The basal fetal heart rate, accelerations, decelerations and amplitude and frequency of variation were scored in positive stress tests of 146 and in suspicious recordings of 296 patients. Positive tests scored lower for accelerations, decelerations and amplitude and frequency of variation but not for the basal heart rate. When the outcome was poor, as characterized by low 5-min Apgar score and intrauterine growth retardation, it was reflected by all parameters of the fetal heart rate pattern except for the basal heart rate. PMID- 2880769 TI - Yugoslavian experience with the contraceptive sponge. AB - A trial of the contraceptive sponge was conducted at two clinics (403 subjects) in Yugoslavia. Women were periodically followed up for 1 year. The 1-year method pregnancy rate (life-table) was 5.6 per 100 women. Rates of other events leading to discontinuation of sponge use were similarly low. There were no serious complications. The results of the study show that the contraceptive sponge may be successfully used by a population of women with limited experience with the use of vaginal contraceptive methods. PMID- 2880770 TI - The effect of an oral contraceptive containing ethinylestradiol and desogestrel on hair growth and hormonal parameters of hirsute women. AB - A group of 22 hirsute women was treated with a combination of 0.030 mg of ethinylestradiol and 0.150 mg of desogestrel (EE-DG) for 6 or 12 months. After 6 months the hair growth was decreased in 17 patients. There was a significant decrease in testosterone/sex hormone binding globulin (T/SHBG) ratio and serum dehydroepiandrosterone sulphate (DHEAS) levels. The changes in the hirsutism and the T/SHBG ratio showed correlation (rho 0.36, P less than 0.05). The patient groups with the best and the poorest clinical response differed in terms of summed changes in the T/SHBG ratio and DHEAS. These findings suggest that the therapeutic effect of the EE-DG is based on combined changes in the related hormone levels. PMID- 2880772 TI - Transcatheter embolization of pelvic arteries as the safest method for postpartum hemorrhage. AB - Two cases of intractable postpartum hemorrhage could be controlled by Gelfoam embolization via an angiographic catheter. The data presented here indicate that transcatheter embolization for postpartum hemorrhage is a safe and effective method compared to surgical ligation of the injured artery. PMID- 2880771 TI - Acute rupture of an ovarian pregnancy associated with a negative serum B-HCG. AB - A case of acute rupture of an ovarian pregnancy in which Beta Subunit of human chorionic gonadotropin was negative is presented. This is the first case known in the literature. Clinical and laboratory aspects of ovarian pregnancy are reviewed. PMID- 2880773 TI - Ectopic pregnancy presenting as intermittent rectal bleeding and anemia. A case report. AB - A case report is presented of a patient with anemia and intermittent rectal hemorrhage caused by a tubal pregnancy eroding into the rectum. A search through the clinical literature on ectopic gestation reveals the rarity of such an occurrence. PMID- 2880774 TI - Tubal pregnancy with patent tube diagnosed by hysterosalpingography. AB - A demonstration of patent tube usually excludes the presence of tubal pregnancy. In the reported case tubal patency was demonstrated by hysterosalpingography in the presence of 6 weeks tubal pregnancy. PMID- 2880775 TI - Regulation of hepatic glutamine metabolism. PMID- 2880777 TI - Effect of prostaglandin PGE2 on alcohol-induced ulceration in the rat colon. AB - The effect of pretreatment with topical prostaglandin E2, prednisolone and sulphasalazine in experimental colitis has been examined in the rat colon. Only prostaglandin E2 treatment significantly reduced mucosal ulceration. Long-term exposure of the rat colon to topical ethanol produced some of the histological changes seen in human colitis. PMID- 2880776 TI - Cytoplasmic reorganization during the resumption of meiosis in cultured preovulatory rat oocytes. AB - Changes in organelle topography and microtubule configuration have been studied during the resumption and progression of meiosis in cultured preovulatory rat oocytes. Germinal vesicle breakdown (GVBD) was reversibly inhibited by dibutyryl cAMP (DcAMP) or nocodazole, a microtubule-disrupting agent. The microtubule stabilizing agent taxol did not inhibit GVBD, but did impair further maturation. The migration of acidic organelles and chromatin in living oocytes was analyzed using the vital stains acridine orange and Hoechst 33258, respectively. Germinal vesicle stage oocytes undergo perinuclear aggregation of acidic organelles during GVBD and these organelles subsequently disperse into the cell cortex as the first meiotic spindle migrates to the oocyte periphery. DcAMP and nocodazole block the perinuclear aggregation of acidic organelles, whereas, in taxol-treated oocytes, organelle aggregation and GVBD occur but the dispersion of acidic organelles was arrested. Dose-response studies on the effects of nocodazole showed that GVBD was generally retarded and that a 50% inhibition of GVBD was achieved at concentrations in excess of 1.0 microM. Concentrations of taxol at 10 microM or above effectively inhibited both chromatin condensation and meiotic spindle formation. Indirect immunofluorescence microscopy with anti-tubulin antibodies revealed dissolution of microtubules with 1.0 microM nocodazole. Taxol had little effect on microtubule organization in germinal vesicle or chromatin condensation stage oocytes; however, when oocytes that had formed first meiotic spindles were treated with taxol, numerous microtubule asters appeared which were preferentially associated with the oocyte cortex. The changes in organelle topography, microtubule configuration, and drug sensitivity are discussed with respect to the regulation of cytoplasmic reorganization during the meiotic maturation of rat preovulatory oocytes. PMID- 2880779 TI - [Psychophysiologic aspect of regulating dyadic interpersonal interaction]. PMID- 2880778 TI - Differential effect of growth factors on growth stimulation and phenotypic stability of glutamine-synthetase-positive and -negative hepatocytes in primary culture. AB - In rat liver parenchyma, two subpopulations of hepatocytes can be distinguished by the absence or presence of the marker enzyme, glutamine synthetase (GS). Hepatocytes in the perivenous zone immediately adjacent to the hepatic venules in the liver acinus are positive for GS. Using autoradiography in combination with immunocytochemistry, the response of these two hepatocyte populations (GS positive and GS negative) to a variety of growth factors (defined compounds or complex stimuli) was investigated in vitro. Irrespective of the individual growth promoting activity (which varied considerably), all stimuli led to much higher labeling indices in GS-negative cells as compared to GS-positive cells. In GS negative cells, the strongest effect was exerted by serum obtained from partially hepatectomized rats (labeling index, 67%) and the conditioned media of JM1 and JM2 hepatoma cells (63%-82%), followed by a combination of insulin and either norepinephrine (46%) or epidermal growth factor (EGF; 42%). In contrast, serum had the weakest influence on GS-positive cells (0.3%), while the other potent stimuli enhanced the labeling index of these cells by between 6% and 15% within 48 h. The percentage of labeled nuclei was higher in mononucleated than in binucleated GS-positive hepatocytes. The time course of thymidine incorporation was also different for the two subpopulations. Under all growth-promoting conditions, the stimulation of GS-negative cells peaked between 72 and 96 h, while it increased continuously in GS-positive cells for at least 120 h, particularly in the case of serum. In proliferating cultures, both the absolute and the relative number of GS-positive hepatocytes decreased, while no such effect was found in various nonproliferating control cultures maintained at low and high cell density. Similar results were found for GS activity. In contrast, the hormonal induction of tyrosine aminotransferase (TAT) was not affected. It is suggested that these differences in the growth response of GS-positive and negative cells contribute to the acinar gradient in hepatocyte proliferation that occurs during liver regeneration. Furthermore, the striking phenotypic instability of GS-positive cells that have undergone DNA synthesis and mitosis supports the hypothesis that cellular reprogramming depends on passage through the cell cycle. PMID- 2880780 TI - Plasma levels of gastrin, somatostatin, and cholecystokinin immunoreactivity during pregnancy and lactation in dogs. AB - Plasma levels of gastrinlike, somatostatinlike, and cholecystokininlike immunoreactivity were determined by radioimmunoassay in peripheral blood from 11 beagles during pregnancy and in response to suckling during lactation. Cholecystokinin was determined in pooled and in individual plasma samples after separation of cholecystokinin and gastrin by high-performance liquid chromatography. Gastrin and somatostatin levels were significantly increased during the 8-wk-long dog pregnancy; peak values were recorded in week 7 and week 4, respectively. The cholecystokinin level rose and peaked at week 3, and remained elevated. In response to suckling, maternal gastrin levels rose significantly when tested in week 1 and 3 of lactation. Somatostatin levels did not respond significantly to suckling, but basal levels were elevated in week 1 compared to week 3 of lactation. Cholecystokinin rose in response to suckling both in week 1 and 3 of lactation. We suggest that the increased levels of gastrointestinal hormones during pregnancy and lactation may serve to increase digestive and anabolic capacity. PMID- 2880781 TI - Inhibition of growth hormone secretion in anaesthetized fowl: hypothalamic participation. AB - Sodium pentobarbitone anaesthesia lowered the circulating growth hormone (GH) concentration in immature chickens and reduced basal and stimulated pituitary GH release in vitro. The immunoneutralization of endogenous somatostatin (SRIF), by passive SRIF immunization, overcame the inhibitory effect of anaesthesia on basal GH secretion in vivo, but had no direct effects on GH release in vitro. However, while SRIF immunization restored the resting GH concentration in the anaesthetized birds, it increased greatly the GH level in conscious birds. These results therefore suggest that the inhibition of GH secretion in anaesthetized birds may be partly SRIF-mediated, although a suppression of hypothalamic stimulation may also be involved. PMID- 2880782 TI - [Treatment of hypertension in pregnancy]. PMID- 2880783 TI - [Neurochemical and endocrine changes in the premenopausal and post-menopausal period]. PMID- 2880784 TI - [Subdural empyema caused by hematogenous spread]. PMID- 2880786 TI - [Modern concepts in the treatment of ischemic heart disease. International symposium. Munich, 27-28 November 1986. Abstracts]. PMID- 2880785 TI - The relationship of injuries of the leg, foot, and ankle to proximal thigh strength in athletes. AB - Rehabilitation programs designed to restore leg, ankle, and foot function following injury frequently ignore the proximal muscles. During athletics, these knee, hip, and trunk muscles derive much of their functional power from the foot and ankle. They also serve to integrate distal segment motions into a total movement pattern such as jumping, running, or kicking. The linkage system, which is a theoretical concept, describes the normal biomechanical and physiological interactions between proximal and distal musculoskeletal structures. Immobilization or injury of distal segments interrupts the normal generation, summation, and transmission of muscular forces across joints. Adequate measures must be taken to properly assess proximal structures for weakness and tightness and to prescribe specific exercises to prevent the migration of the effects of injury away from the involved segment. PMID- 2880787 TI - [A case of malignant neuroleptic syndrome with rhabdomyolysis and a therapeutic trial using physostigmine]. AB - We report the case of a 22-year-old schizophrenic patient who developed a neuroleptic malignant syndrome under treatment with Benperidol, Levomepromazin and Biperiden. Clinical signs were: fever, rigidity, altered consciousness and rhabdomyolysis of hip-abductors. Intravenous injection of physostigmine led to clearing of consciousness, whereas there seemed to be no impact on fever and rigidity. PMID- 2880788 TI - [Effects of alcohol consumption on blood pressure levels in Hisayama residents. Part 2. Relationship between time-related changes in blood pressure and those in levels of gamma-glutamyl transpeptidase]. PMID- 2880789 TI - [Rat lymphoid cell lines producing human T cell leukemia virus-I]. AB - Cocultivation of spleen cells, lymph node cells, and thymocytes of female Wistar King-Aptekman rats with short-term cultured male adult T cell leukemia (ATL) cells in the presence of 5-bromo-2'-deoxyuridine (BudR) resulted in the establishment of rat lymphoid cell lines, TARS-1, TARL-2, and TART-1. Cytogenic analysis of the three cell lines showed a female rat karyotype with 42 chromosomes. The surface phenotypes of TARS-1 and TART-1 were those of rat T cells. TARL-2 was only positive for rat Ia and leukocyte common antigens and brain associated T antigen. The cell lines continuously produced a type C retrovirus, human T cell leukemia virus-I (HTLV-I) and expressed ATL-associated antigens. By using monoclonal antibodies for rat IL-2 receptors, FACS analysis demonstrated that three rat T cell lines unequivocally expressed rat IL-2 receptor. TARS-1 and TART-1 but not TARL-2 were transplantable into newborn syngeneic rats and nude mice. By injecting MMC-treated TARS-1 into newborn syngeneic rats, HTLV-I carrier rats were obtained which showed gradual increase of anti-ATLA antibody titer by aging. No evidence of leukemia nor malignant lymphoma were observed in those carrier rats. Adult rats immunized with these rat cell lines produced antibodies specific for HTLV-I. The biochemical analysis of the antigen that reacted with rat sera revealed that they are the HTLV-I specific polypeptides, p28, p24, p19 and p15. PMID- 2880790 TI - Further characterization of thyrotropin-displacing-activity (TDA): evidence of restricted heterogeneity. AB - For further characterization immunoglobulins G (IgG) of 14 patients with Graves' disease were fractionated on Protein A bound Sepharose. Sufficiently enriched IgG subclasses were obtained despite incomplete separation. TSH displacing activity (TDA) was not homogeneously distributed in the subclasses, however IgG1 was most predominant in TDA followed by IgG3, IgG2 being essentially inactive. In two subjects TDA in whole IgG gave positive results in subclasses after fractionation, thus providing evidence, that it would be theoretically possible to move sensitivity of the method close to 100% after subfractionation. TDA was not enriched together with thyroid cell antibodies. We conclude from these results that TDA-IgG is characterized by restricted heterogeneity notwithstanding the incomplete separation of the IgG-subclasses. PMID- 2880791 TI - Clinical and pathologic features of polyarteritis nodosa and its renal-limited variant: primary crescentic and necrotizing glomerulonephritis. AB - This study supports the concept that primary necrotizing and crescentic glomerulonephritis is a kidney-limited form of polyarteritis nodosa. Thirty-four patients with necrotizing and crescentic glomerulonephritis were divided into three groups based on the presence or absence of systemic vasculitis as determined by clinical or histologic criteria. Laboratory studies demonstrated elevated erythrocyte sedimentation rates, anemia, mild eosinophilia, hematuria, and proteinuria in patients in each group; there were no significant differences in these data between the groups, however. Complement levels and antinuclear antibody screens were normal. Mean serum creatinine levels were markedly elevated but fell by a factor of two following therapy. There was a higher morbidity in the patients with kidney-limited disease. This was attributable to a higher percentage of these patients' having no symptoms and presenting for medical care only after they were in chronic renal failure. Most patients not experiencing chronic renal failure were treated with cyclophosphamide and prednisone, which seemed effective in this retrospective study. PMID- 2880792 TI - A simple DNA diagnostic method for human genetic disorders. AB - A fast, reliable, and simple technique for detecting point mutations in unfractionated human DNA has been developed. Oligonucleotide probes complementary to either sickle- or normal beta-globin DNA are labeled by primer extension and hybridized to DNA applied to nitrocellulose paper in a dot-blot format. A short hybridization time (about 1 h) and low probe concentration (about 1 nM) yield low background and high specificity. Double-blind trials show 100% agreement with restriction fragment length polymorphism (RFLP) analysis of DNA from normal, sickle, and heterozygous subjects. PMID- 2880793 TI - Localization of a human heat-shock HSP 70 gene sequence to chromosome 6 and detection of two other loci by somatic-cell hybrid and restriction fragment length polymorphism analysis. AB - The human 70 kdalton heat-shock protein (HSP 70) is a member of a multigene family which is expressed in response to various physiological stresses including elevated temperatures. Using a cloned genomic HSP 70 DNA sequence we demonstrate by somatic cell hybrid and restriction fragment length polymorphism (RFLP) analyses that there are a minimum of three distinct HSP 70 loci in the human genome, one of which is located on chromosome 6. PMID- 2880794 TI - Regional localization and characterization of a DNA segment on the long arm of chromosome 21. AB - A human genomic DNA fragment, pAM37 (HGM8; D21S22), was mapped to chromosome 21q2.1-q2.21 by in situ hybridization. This segment is therefore situated on the boundary of the "pathological region" of Down syndrome. A genomic restriction map encompassing 35 kb of chromosome 21 was derived and two restriction fragment length polymorphisms (RFLPs) were mapped and characterized. A homologous sequence was detected in the mouse genome but no homologous RNA was detected in a range of human tissues. This DNA segment will contribute to the linkage mapping of chromosome 21 and will facilitate delineation of the pathological region of Down syndrome. PMID- 2880795 TI - [Effect of applications of TPA for GGT-positive foci during DMBA-induced cheek pouch carcinogenesis of the hamster]. PMID- 2880796 TI - Synthetic sulpholipopolysaccharides: novel adjuvants for humoral immune responses. AB - Referring to the strong immunostimulating activity of combinations of lipophilic agents and dextran sulphate, conjugates with chemical determinants of both types of adjuvants were synthesized and then examined for immunostimulatory capabilities in mice. Saturated fatty acids with varying chain lengths and sulphate groups were coupled covalently at defined ratios to the polysaccharide Ficoll (MW 400,000). Chemical analysis of 60 of the sulpholipopolysaccharides synthesized revealed that the number of sulphate groups per monosaccharide unit varied from 0 to 1.6, and the number of lipid groups from 0 to 0.8. Adjuvanticity of these conjugates for the humoral immune response was determined using sheep red blood cells (SRBC) and dinitrophenyl-haptenated bovine serum albumin (DNP BSA) as antigens. Five days after intraperitoneal injection of adjuvant and antigen, the numbers of direct anti-SRBC plaque-forming cells (PFC) in the spleen were determined. Anti-DNP antibody titres were measured from 1 to 4 weeks after immunization. PFC responses to 2 X 10(6) SRBC were augmented up to a 100-fold by conjugates of Ficoll and sulphate (sulphopolysaccharides: SPs) or lipid groups (lipopolysaccharides: LPs). Introduction of low or moderate numbers of lipid groups in SPs reduced adjuvanticity. Adjuvant activity of sulpholipopolysaccharides (SLPs) with varying sulphate and high lipid content depended on the sulphate contents and the chain length of the lipids. Sulphate reduced adjuvanticity of the SLPs, and the number of sulphate groups required for complete annihilation increased with the chain length of the lipid. LPs and SLPs, including conjugates that did not enhance anti-SRBC PFC responses, augmented serum antibody responses to DNP-BSA while SPs were hardly effective. PMID- 2880797 TI - Mapping of the mouse Ly-6, Xp-14, and Gdc-1 loci to chromosome 15. AB - The Ly-6 locus is now regarded as a gene complex consisting of at least five closely linked loci (Ly-6A-Ly-6E) whose polymorphic products are identified by monoclonal antibodies and distinguished by different tissue distributions. Ly-6 has been assigned by other investigators to chromosome (Chr) 9 (linked to Thy-1) or to Chr 2. We report that the Ly-6 gene complex, together with the Xp-14 and Gdc-1 loci, is situated on Chr 15 linked to Gpt-1. These new linkage data are derived from four sources: (1) three separate crosses that failed to demonstrate linkage of Ly-6 to either Thy-1 on Chr 9 or to any of five genes present on Chr 2; (2) the NXSM recombinant inbred strains, which suggested the linkage of Ly-6 and Xp-14 to Gpt-1 on Chr 15; (3) several Gpt-1 and Gdc-1 congenic strains that confirmed the assignment of Ly-6 and Xp-14 to Chr 15; and (4) backcrosses that further confirmed the linkage of Ly-6, Gpt-1, Gdc-1, and Xp-14, the probable gene order being Gpt-1/Ly-6-Xp-14-Gdc-1. PMID- 2880798 TI - A mutant lymphoma cell line with a defective Thy-1 glycoprotein gene. AB - We characterized a mutant T-cell lymphoma line selected for the inability to express the Thy-1 glycoprotein. This cell line is a member of the D complementation class of Thy-1- somatic cell mutants, and it lacks detectable cell-surface Thy-1.1 glycoprotein and detectable cytoplasmic Thy-1 mRNA. Southern blot analysis using a number of probes isolated from the cloned Thy-1.2 gene demonstrated that, in the mutant, one copy of the Thy-1 gene is absent from the genome and the other has undergone rearrangement. This rearrangement results from a deletion of the 5' portion of the gene removing the first two alternate exons and promoters and a portion of the second intron. The deletion breakpoint within the mutant Thy-1 gene was localized to within 400 nucleotides by Southern blot analysis. The breakpoint is near two classes of mouse repetitive elements-a mouse B1-family repetitive element and a simple repetitive sequence-suggesting a mechanism of rearrangement leading to the mutation. Southern blot analysis demonstrated that two closely linked molecular markers on chromosome 9 are unaltered, demonstrating that the deletion in this mutant cell line is subchromosomal. PMID- 2880800 TI - Identification of a new HLA-B7-associated C21-hydroxylase deficiency gene by restriction enzyme length polymorphism. PMID- 2880799 TI - Analysis of the equine lymphocyte antigen system by Southern blot hybridization. AB - Fourteen Standardbred horses homozygous for one of six equine lymphocyte antigen (ELA) specificities (A1, A3, A4, A5, A6, or A10) were analyzed by Southern blot hybridization using DNA probes derived from the mouse major histocompatibility complex (MHC). Total genomic DNA from peripheral lymphocytes was digested with the restriction enzymes Hind III, Pvu II, or Eco RI. Twenty-three to thirty-three bands were generated for individual horses with the class I cDNA probe. The resulting band patterns revealed 12-14 nonpolymorphic fragments, which is consistent with the highly conserved Qa/Tla genes seen in other species. The remaining 10-19 bands displayed significant polymorphism; no two animals had identical band patterns when studied with all three enzymes. The polymorphism was markedly decreased between animals of the same ELA serotypes. Unique bands were identified in both A1 horses and all four A6 animals. Pvu II digestions of lymphocyte DNA were hybridized with mouse MHC class II probes. A cDNA probe for the E alpha gene revealed only a single nonpolymorphic band. In contrast, a cDNA probe for the H-2 A alpha locus displayed three to five strong bands in each animal with polymorphism that was most pronounced between horses of different ELA serotypes. Genomic DNA probes for A beta and E beta genes both revealed multiple polymorphic bands. However, cross-hybridization between these two probes prevented distinction between A beta and E beta equivalent loci. The reduced polymorphism evident within ELA specificities is consistent with the concept that the equine lymphocyte antigen system includes two families of closely linked MHC genes. PMID- 2880802 TI - In vivo effect of histamine & acetylcholine on the virulence of Entamoeba histolytica. PMID- 2880801 TI - HLA-D/DR-BON: a new biochemically and cellularly defined polymorphism indistinguishable by RFLP from DR1. PMID- 2880803 TI - Segmental action of epidural narcotics. PMID- 2880804 TI - Is beta 1-antagonism essential for the antihypertensive action of beta-blockers? AB - Both nonselective beta-blockers and beta 1-selective blockers are effective antihypertensive agents. beta 1-Blockade generally is considered to be responsible for their antihypertensive action, whereas beta 2-blockade is regarded as undesirable. These common assumptions notwithstanding, the mechanism by which beta-blockers lower blood pressure remains unknown. To examine the possibility that beta 2-blockade may contribute to the antihypertensive action of beta-blocker therapy, we studied the cardiovascular effects of compound ICI 118551, a beta 2-selective blocker. First, we showed that 50 mg t.i.d. orally is a beta 2-selective dose. In contrast to propranolol, 80 mg t.i.d., or atenolol, 100 mg once a day, 50 mg of ICI 118551 t.i.d. failed to block beta 1-mediated inotropic stimulation and stimulation of renin by isoproterenol. We then performed a double-blind, placebo-controlled trial in patients with mild essential hypertension to compare this compound with propranolol, 80 mg t.i.d., and showed that ICI 118551 significantly decreased systolic and diastolic blood pressure. This antihypertensive effect was demonstrated by direct as well as by indirect blood pressure measurements. Thus, contrary to prevailing thought, beta 2-blockade has an antihypertensive effect independent of, and distinct from, beta 1-blockade. PMID- 2880805 TI - Investigation of some effects of levamisole on dog blood pressure. AB - The effects of levamisole were investigated on the blood pressure of anaesthetized dog. Levamisole (0.5 to 4.0 mg/kg) elicited a biphasic effect, an initial brief depressor response followed by a pressor response. The pressor response was dose-related and was blocked by phenoxybenzamine. The residual depressor response was blocked by propranolol. Repeated administration of a high dose of levamisole produced tachyphylaxis. The pressor response to levamisole was not modified by either reserpinization, acute bilateral adrenalectomy or pretreatment with cocaine, whereas pretreatment with dexamethasone, nialamide or pyroaallol shifted the dose-response curve to the right. Levamisole potentiated the pressor responses to noradrenaline, angiotensin and acetylcholine. The effects of levamisole are ascribed to inhibition of monoamine oxidase, catechol-O methyl transferase, catecholamine uptake2 mechanism and cholinesterase. PMID- 2880806 TI - Stimulation of human polymorphonuclear leukocyte oxidative metabolism by type 1 pili from Escherichia coli. AB - We compared the degree to which Escherichia coli phase variants which do (T1P+ E. coli) or do not (T1P- E. coli) express type 1 pili (T1P) stimulate human polymorphonuclear leukocyte (PMN) oxidative activity. Unopsonized T1P+ E. coli stimulated the release of 0.20 to 0.24 nmol of H2O2 per 10(6) PMN per min and the consumption of 1.4 to 4.0 nmol of O2 per 10(6) PMN per min; no measurable PMN oxidative activity was stimulated by unopsonized T1P- E. coli. In the presence of serum opsonins, T1P+ E. coli stimulated the release of 1.12 to 1.16 nmol of H2O2 per 10(6) PMN per min and the consumption of 5.0 to 6.0 nmol of O2 per 10(6) PMN per min, whereas T1P- E. coli stimulated the release of 0.42 to 0.43 nmol of H2O2 per 10(6) PMN per min and the consumption of 0.6 to 2.0 nmol of O2 per 10(6) PMN per min. Although unaggregated T1P did not stimulate PMN, latex beads coated with T1P (T1P-latex) stimulated alpha-methylmannoside-inhibitable, opsonin-independent PMN oxidative activity. The activity stimulated by either T1P+ E. coli or T1P latex was susceptible to inhibition by cytochalasin B. Latex particles coated with bovine serum albumin or mannose-resistant pili did not stimulate PMN. These data indicate that T1P+ E. coli stimulate PMN oxidative metabolism more effectively than do T1P- E. coli and that a similar PMN oxidative response follows cellular stimulation by either unopsonized T1P+ or opsonized T1P- E. coli. Furthermore, T1P-latex faithfully mimics the ability of T1P+ E. coli to stimulate PMN oxidative metabolism. Such particles may be useful in further analyses of cellular responses to T1P+ E. coli. PMID- 2880807 TI - F41 pili as protective antigens of enterotoxigenic Escherichia coli that produce F41, K99, or both pilus antigens. AB - Pigs suckling dams that have been vaccinated with pilus antigen are protected against challenge with enterotoxigenic Escherichia coli (ETEC) strains that express the same pilus antigen. However, some ETEC strains express more than one pilus antigen. Pregnant swine were vaccinated either with E. coli HB101 that harbored a recombinant plasmid coding for F41 expression (F41+) or with the HB101 parent strain that carries the pHC79 vector (F41-). Suckling pigs born to vaccinated dams were challenged with ETEC that expressed either K99, F41, or both pilus antigens. Production of F41 in vivo was demonstrated by immunofluorescence assay of sections of ileum and by seroconversion against F41 antigen by pigs challenged with F41+ and K99+ F41+ ETEC strains. The F41+ vaccine protected against challenge with an F41+ ETEC strain. In contrast, F41+ vaccination did not protect against challenge with K99+ or K99+ F41+ ETEC strains. The F41- vaccine did not protect against challenge with any strain used. The results indicate that K99+ F41+ ETEC strains produce F41 antigen in the small intestine during disease and that F41+ vaccination can be a protective antigen if the challenge strain expresses only F41 antigen, but that F41+ vaccination may not protect against strains that produce both K99 and F41 antigens. PMID- 2880809 TI - Sclerosing encapsulating peritonitis. PMID- 2880808 TI - Pseudomonas aeruginosa adhesins for tracheobronchial mucin. AB - Mucins of the tracheobronchial tree are preferential sites for adherence and colonization by Pseudomonas aeruginosa. They possess specific receptors for this organism that have amino sugars as their principal constituents. Since mucins probably reflect the receptors on the cellular surfaces, we hypothesized that the bacterial adhesins previously shown to mediate the binding of P. aeruginosa to cells would also mediate bacterial binding to mucins. We therefore tested the roles of the exopolysaccharide from mucoid strains of P. aeruginosa and pili from nonmucoid strains to see whether they are indeed the adhesins for mucins. Using a microtiter plate assay of adherence to mucins, we demonstrated that the mucoid exopolysaccharide bound to mucins and enhanced the adherence of mucoid strains to this substance. Antibodies raised against the exopolysaccharide from a single mucoid strain inhibited the adherence of all mucoid strains tested. Purified pili from nonmucoid strains inhibited the binding of nonmucoid strains but not of mucoid strains. Inhibition of adherence by antibody to pili was quite specific, antibody being able to inhibit only the binding of the homologous nonmucoid strain. These data support our previous observations with tracheal cells, confirming the similarity of the adhesins for respiratory tract cells and the mucins which cover them. PMID- 2880810 TI - Renal hemodynamic changes after beta-blocker-diuretic combination therapy in azotemic hypertensive patients. AB - The effects of beta-blocker therapy with either nadolol or propranolol were compared during therapy with hydrochlorothiazide (HCTZ) 50 mg b.i.d. on glomerular filtration rate (GFR), effective renal plasma flow (ERPF), effective renal blood flow (ERBF), blood pressure, and heart rate in 22 patients with essential hypertension and mild to moderate renal insufficiency. The clearances of inulin and para-aminohippurate (PAH) were used to estimate renal hemodynamic measurements. These parameters were determined after 2 weeks of HCTZ plus placebo and at 1, 3, and 6 months after the addition of beta-blocker to HCTZ. Significant reductions in blood pressure and heart rate were seen, but no significant reduction of renal hemodynamics were seen with either beta-blocker-HCTZ combination. Since 50% of the patients in each drug group were either Black or White, hemodynamic data were also analyzed by race. One month after beta-blocker addition there was a slight reduction of GFR in both Whites (47 +/- 6 vs. 40 +/- 5 ml/min, p greater than .05) and Blacks (44 +/- 5 vs. 40 +/- 6 ml/min, p less than .05). By month 6, GFR in Whites rose to 57 +/- 9 ml/min, whereas in Blacks it fell significantly to 36 +/- 6 ml/min (p less than .01). Similarly, at month 1, ERBF declined by 12% and 13% in Whites and Blacks, respectively. However, at month 6, ERBF rose by 28% in Whites and remained 11% lower in Blacks, p less than .05. In summary, in the group as a whole neither beta-blocker significantly altered renal hemodynamics when added to HCTZ therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2880811 TI - Suanzaorentang versus diazepam: a controlled double-blind study in anxiety. AB - The ancient Chinese remedy Suanzaorentang was originally described in Kin-Kue-Yao Lueh for patients with weakness, irritability and insomnia. In our preliminary observations on suanzaorentang, it seemed to be a promising anxiolytic remedy. A controlled comparative double-blind clinical trial was set up to assess the anxiolytic effect of suanzaorentang. Suanzaorentang (250 mg t.i.d.) and diazepam (2 mg t.i.d.) had almost the same anxiolytic effect. However, suanzaorentang, but not diazepam, improved the psychomotor performance during the daytime. No significant subjective side effects were observed during treatment with suanzaorentang. All laboratory tests, including liver function tests (serum SGOT, SGPT, albumin, globulin, bilirubin), renal function tests (BUN, serum creatinine), electrolyte balances (serum K+, Na+, Cl-, Ca++), serum cholesterol triglyceride-HDL-c, thyroid function test (serum T4), chest P-A X-ray film, blood urine-stool routine examinations (BUS routines), were unaltered after one week's administration of the compound. PMID- 2880812 TI - Pelvic inflammatory disease, laparoscopy, and the expenditure of health care dollars. PMID- 2880813 TI - Usefulness of double-puncture laparoscopy in the infertility work-up. AB - This retrospective study confirms that laparoscopy should be performed early in the infertility investigation when pelvic pathology is suspected. If performed, the procedure should be via the double-puncture technique. Otherwise, it should be done when the rest of the tests have proven to be within normal limits and there is only the possibility of peritoneal involvement (i.e., pelvic adhesions or pelvic endometriosis). Our impression is that the single-puncture technique seriously compromises the physician's ability to assess pelvic pathology adequately. PMID- 2880814 TI - Low-dose spironolactone in the treatment of female hirsutism. AB - Twelve women, 11 with hirsutism and one with alopecia areata, were treated with low-dose spironolactone (50 mg daily) from the 4th until the 22nd cycle day over 12 consecutive menstrual cycles. Eight hirsute women observed a favorable effect on hirsutism in 3 to 8 months, and hair loss ceased in the one patient with alopecia areata. No significant side effects occurred. Low-dose spironolactone decreased the concentration of total and free testosterone and elevated the concentration of prolactin on the 10th cycle day, while LH, FSH, estradiol, progesterone, DHEAS, SHBG, and cortisol levels remained unchanged. The plasma aldosterone concentration increased significantly during the treatment, although serum potassium and sodium concentrations remained unchanged. Low-dose spironolactone is, thus, safe and effective in the treatment of hirsutism. It seems to be useful as an initial or alternative treatment. PMID- 2880815 TI - The reproductive performance of women before and after metroplasty. AB - Nineteen women with congenital uterine anomalies underwent metroplasty. Prior to surgical correction of the uterine malformation, 44 of their 45 (98%) pregnancies had ended with a spontaneous abortion, and no woman had a living child. Following metroplasty, only 4 of 18 (22%) pregnancies aborted, and 12 of the 14 (86%) women attempting pregnancy had a living child. There were no unusual intraoperative or postoperative complications. Metroplasty procedures can be performed safely, and are associated with excellent reproductive outcomes. PMID- 2880817 TI - Familial 46,XX gonadal dysgenesis. AB - Two sisters, ages 18 and 25, presented with primary amenorrhea and underwent clinical, hormonal, cytogenetic, and pathologic evaluation. Both were of normal stature and lacking of somatic stigmata. Both patients had normal 46,XX karyotype on peripheral blood. Streak gonads were seen in both patients and a rather scanty number of primordial follicles was found in one patient. FSH, LH, and urinary estrogens were consistent with streak gonad syndrome. Autosomal recessive inheritance has been suggested in familial aggregates with XX gonadal dysgenesis. PMID- 2880816 TI - Hormone study in a case of Klinefelter syndrome with an isochromosome Xq. AB - We investigated the endocrine function of a patient with Klinefelter syndrome in which the extra chromosome was an isochromosome Xq. This man was azoospermic but with normal secondary sex characteristics; smallness of the testes was the only abnormal physical finding. High follicle-stimulating hormone (FSH, 70 mIU/mL) and moderately elevated luteinizing hormone (LH, 40 mIU/mL) were found; the FSH and LH response to LH-RH was exaggerated. Androgen and estrogen levels were normal. The insulin test (measure of glycemia, growth hormone, and corticol) and the test with TRH (measure of TSH and prolactin) gave normal results. We conclude that the presence of additional long arms of the X chromosome is sufficient to cause Klinefelter syndrome and that the presence of two extra Xq does not intensify the degree of androgenic insufficiency. PMID- 2880819 TI - Induction of ovulation in polycystic ovary: human menopausal gonadotropin or human urinary follicle stimulating hormone? AB - One group of 21 and one group of 22 anovulatory women with polycystic ovaries (PCO) underwent induction of ovulation with human urinary follicle stimulating hormone (HU-FSH)/human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG)/HCG, respectively. No statistically significant differences in ovulation rate were found between patients treated with HU-FSH (95.2%) and those treated with HMG (100%). Eight (38.1%) and 11 (50.0%) patients conceived, six (28.5%) and eight (36.3%) delivered, and two (9.5%) and three (13.6%) aborted with HU-FSH and HMG, respectively. No multiple pregnancies occurred. Serum 17 beta-estradiol (E2) levels and the number of maturing follicles prior to HCG injection were significantly higher with HU-FSH than HMG, while there were no differences in the diameter of the dominant follicle before HCG. Ovarian hyperstimulations were discovered more frequently after HU-FSH/HCG (40%) than HMG/HCG treatments (22.2%). These data do not confirm an effective advantage in the use of HU-FSH in ovulation induction in cases of PCO. PMID- 2880818 TI - Sperm antibodies and human leukocyte antigens in couples with early spontaneous abortions. AB - Twenty-six couples with two or more early spontaneous abortions and 53 couples with recently proven fertility (control group) were typed for human leukocyte antigens (HLA) of A and B loci and screened for the presence of cytotoxic and hemagglutinating antibodies to sperm. Eighteen other couples with two or more abortions were tested for sperm antibodies alone. Both partners in 24 of 44 (54%) aborting couples were positive (titers of greater than or equal to 32), whereas the control group had sperm antibodies in the negative range (titers of 0 to 16; P less than .0001). Thirty-one husbands (70%) and 24 wives (54%) were positive for sperm antibodies in the study group. Sharing of HLA-A and/or -B antigens between partners was similar in the control and study groups. Fourteen of 26 (54%) couples with two or more abortions did not share HLA-A and/or -B antigens, in contrast to 14 of 53 (26%) in the control fertile group (P less than .02). Antigenic frequencies of HLA-B7 singly and in combination with HLA-B35 were increased in females in the aborting but not in the fertile control group (P less than .001). The combined incidence of HLA-B7, -B8, and -B35 in both partners was significantly higher in the aborting couples as contrasted with the control group. It is suggested that the presence of sperm antibodies is associated with early pregnancy wastage. Histocompatibility antigens B7 and B35 may play a role through their association with sperm antibodies and early spontaneous abortions. PMID- 2880821 TI - The structural specificity of carbohydrate in the initiation of rat sperm motility. AB - Mammalian spermatozoa are stored in the cauda epididymis (CE) in a quiescent state and become motile when diluted with seminal plasma upon ejaculation. The structural specificity of a variety of sugars and sugar derivatives as diluents that are capable of initiating a transition of CE spermatozoa from the quiescent to the actively motile state was examined. It was found that monosaccharides, except those containing less than five-carbon skeletons, were good motility initiators; a trisaccharide tested showed reduced activity. The initiation activity was also independent of the structural stereospecificity and the nutritional value of the sugar. Based on these observations, a mechanism involving a receptor which handles sugar transport or sugar recognition in a transport process is proposed to be responsible for generating a signal that triggers CE spermatozoal motility. PMID- 2880820 TI - Studies on the constancy of transudated and locally produced proteins in human seminal plasma. AB - An overall constancy in the total protein profile of human seminal plasma (HSP) as determined by gel filtration chromatography and high-resolution electrophoresis was found in six healthy volunteers. Thirteen different proteins were identified by double immunodiffusion in five individual HSP samples each previously subjected to gel filtration. It was also found that comparatively large amounts of yet unidentified low-molecular-weight (less than 12,000) compounds occurred in all HSP samples. Of eight specific proteins in consecutive samples collected from one individual, large intra-individual variations were found in some of the proteins. The largest variations (about 100%), for both concentration and total amount, were noted for alpha 1-antitrypsin, transferrin, IgA, and secretory IgA. Albumin and lactoferrin were rather stable and varied less than 20% between samples. It is suggested that HSP-albumin may be used as a reliable marker of transudation of serum proteins to the genital tract. Likewise, lactoferrin could be used as a marker for the secretion of seminal vesicle proteins, since it reflects the functional status of these glands. PMID- 2880822 TI - Clinical, endocrine, roentgenographic, and immune characterization of hyperprolactinemic women. AB - Seventy-one hyperprolactinemic women were analyzed for medical history, gonadotropin and ovarian hormonal levels, and prolactin (PRL) responsiveness to benserazide. Sellar tomography was then performed on a yearly basis for 3 years in all women, computerized coronal and sagittal tomography in 54 of them. Under basal conditions, 30 women had roentgenographic evidence of pituitary adenoma; at the end of the follow-up period, such evidence was seen in 44. Amenorrhea, steady PRL levels, a low LH/FSH ratio, a longer duration of the disease, and low serum progesterone levels were more common in women with a final diagnosis of pituitary adenoma than in those with a persistently normal sella. The benserazide test for PRL release had yielded abnormal results since the beginning in all the 44 women with final roentgenographic evidence of pituitary adenoma, and in about half of the patients with persistently normal aspect of the sella; autoantibodies towards the pituitary gland, the thyroid gland, and gastric parietal cells were found in 3, 2, and 3 patients, respectively. No autoantibodies towards the adrenal gland or the islets of Langerhans were ever found in any cases. These data show that a fair proportion of hyperprolactinemic women have a (micro)adenoma, which becomes apparent over a relatively short period of time. Amenorrhea and steadily raised PRL levels are more common in these women. The benserazide test seems to be adequate for predicting which women will eventually develop a roentgenographically detectable adenoma. Autoimmunity does not seem to be involved in the pathogenesis of hyperprolactinemia and/or pituitary adenoma. PMID- 2880824 TI - [Abuse of and dependence on benzodiazepines]. PMID- 2880825 TI - [Abuse of and dependence on sedatives and hypnotics]. PMID- 2880826 TI - [Doping]. PMID- 2880823 TI - Enzyme activities of human seminal plasma having different states of coagulation. AB - Aminopeptidase, a chymotrypsin-like enzyme, and alpha-d-glucosidase activites of human seminal plasma were compared amongst four groups of human ejaculates, classified according to initial state of coagulation, i.e., coagulated, fully gelled, partly gelled, and liquid. Liquefaction times of liquid and partly gelled groups were significantly lower than those of the other two groups. Aminopeptidase was significantly higher in liquid and partly gelled groups in comparison with that of coagulated and fully gelled ejaculates. Activities of the other two enzymes did not differ significantly among the four semen groups. PMID- 2880827 TI - Polymorphic DNA markers genetically linked to disease-causing genes: a review. PMID- 2880828 TI - [Immunologic phenotyping of cutaneous lymphomas]. AB - Monoclonal antibodies against lymphoid cell-associated antigens have contributed substantially to our understanding of cutaneous lymphomas. The distribution and function of the most important T- and B-cell antigens are summarized and their expression on cutaneous lymphomas is discussed. Monoclonal antibodies can provide a valuable diagnostic approach to supplement routine histology, especially in histologically doubtful cases. PMID- 2880829 TI - Psychotherapeutic, licit, and illicit use of drugs among adolescents. An epidemiological perspective. AB - Using data from an ongoing series of large national surveys of American high school seniors, levels and trends in the use of a number of classes of drugs are reported for the decade 1975-1985. Among the classes included are the medically supervised and the illicit use of the major psychotherapeutic drugs; the use of illegal drugs such as marijuana, cocaine, hallucinogens, and heroin; and the use of cigarettes and alcohol. Physicians' prescriptions to adolescents for minor tranquilizers, barbiturates, and amphetamines are found to have changed over the decade, with considerably fewer seniors reporting such prescriptions today. The prevalence of prescribed opiate-type drugs remains unchanged. The illicit use of these psychotherapeutics has changed in similar ways, and the hypothesis that there is some causal connection between medically supervised use and non medically supervised use is explored and given some substantiation. Nearly all of the illicitly used drugs have shown some decline in popularity during the past five years, with cocaine use being the notable exception. Alcohol use remained stable at high levels until very recently. Cigarette smoking showed some important declines in the middle of the decade but has since leveled out. PMID- 2880830 TI - Inbred and mutant mice and rats available in Japan with unique contributions to cancer research. PMID- 2880831 TI - Antibodies to human immuno-deficiency virus and human T-cell leukemia virus type I in Japanese patients with hematologic malignancies. AB - One thousand six hundred and seventy-four blood samples drawn between January 1980 and April 1986 from 1454 Japanese, including 251 leukemia, 409 lymphoma, 76 adult T-cell leukemia and 25 benign lymphadenitis patients, were tested for antibodies to HIV and HTLV-I. No patient with lymphadenitis or lymphoma associated with HIV infection was found. In 87 patients with acute and chronic leukemias who had received multiple transfusions, 8 were positive for anti-HTLV-I antibody after blood transfusions amounting to 115 units, on average, while no patient was positive for anti-HIV antibody. Overall, no sample was positive for anti-HIV antibody, whereas 153 (10.5%) were positive for anti-HTLV-I antibody. These results indicate that the transmission of HIV by blood transfusions is far less prevalent than that of HTLV-I in Tokyo at present. PMID- 2880832 TI - Hematologic abnormalities similar to the preleukemic state of adult T-cell leukemia in African green monkeys naturally infected with simian T-cell leukemia virus. AB - Studies were made of the hematologic features of 23 adult African green monkeys (Cercopithecus aethiops) naturally infected with simian T-cell leukemia virus (STLV), which is closely related to human T-cell leukemia virus type I. None of the STLV-infected monkeys showed any clinical signs, but their absolute lymphocyte count and percentage of atypical lymphocytes were significantly higher than those of uninfected monkeys. Three STLV-infected monkeys had especially high percentages of atypical lymphocytes. Most of the atypical lymphocytes were small- or medium-sized lymphocytes with a lobulate or convoluted nucleus, and were very similar to the leukemic cells in human cases of adult T-cell leukemia (ATL), while other atypical cells were large lymphoblastoid cells. Both types of atypical cells were positive for Leu2a and Tac antigens, and expressed STLV antigen after short-term culture. These findings suggested the presence of a preleukemic state in these STLV-infected monkeys similar to that seen in human ATL, and indicated the value of this natural infection system as an animal model of ATL in humans. PMID- 2880833 TI - Effect of sodium butyrate on primary cultures of adult rat hepatocytes. AB - Sodium butyrate, at millimolar concentrations, seems to mediate or initiate multiple effects on many mammalian cells in culture. Although many transformed cell lines respond to butyrate treatment with acquisition of normal cellular characteristics, the effect of butyrate on a normal cell type, the parenchymal hepatocyte, has not been studied. Serum-free primary cultures of adult rat hepatocytes maintain many adult characteristics, yet after several days in culture a loss of adult characteristics occurs while fetal characteristics are often reexpressed. Therefore, we investigated whether butyrate treatment would improve the morphologic and biochemical characteristics of cultured hepatocytes. Exposure to 5 mM butyrate for 3 d did not affect hepatocyte viability or morphology but retarded the progressive decline in cytochrome P-450 levels and 5' nucleotidase activity. The spontaneous increase in alkaline phosphatase activity was reduced and the induction of tyrosine aminotransferase was inhibited after 3 d in culture. The fetal liver characteristic, gamma glutamyltranspeptidase, was not affected by butyrate treatment. Results of this study suggest that butyrate represents a nontoxic compound capable of improving the maintenance of cell culture characteristics of adult rat hepatocytes. PMID- 2880834 TI - DL-7-azatryptophan and citrulline metabolism in the cyanobacterium Anabaena sp. strain 1F. AB - An alternative route for the primary assimilation of ammonia proceeds via glutamine synthetase-carbamyl phosphate synthetase and its inherent glutaminase activity in Anabaena sp. strain 1F, a marine filamentous, heterocystous cyanobacterium. Evidence for the presence of this possible alternative route to glutamate was provided by the use of amino acid analogs as specific enzyme inhibitors, enzymological studies, and radioistopic labeling experiments. The amino acid pool patterns of continuous cultures of Anabaena sp. strain 1F were markedly influenced by the nitrogen source. A relatively high concentration of glutamate was maintained in the amino acid pools of all cultures irrespective of the nitrogen source, reflecting the central role of glutamate in nitrogen metabolism. The addition of 1.0 microM azaserine increased the intracellular pools of glutamate and glutamine. All attempts to detect any enzymatic activity for glutamate synthase by measuring the formation of L-[14C]glutamate from 2-keto [1-14C]glutarate and glutamine failed. The addition of 10 microM DL-7 azatryptophan caused a transient accumulation of intracellular citrulline and alanine which was not affected by the presence of chloramphenicol. The in vitro activity of carbamyl phosphate synthetase and glutaminase increased severalfold in the presence of azatryptophan. Results from radioisotopic labeling experiments with [14C]bicarbonate and L-[1-14C]ornithine also indicated that citrulline was formed via carbamyl phosphate synthetase and ornithine transcarbamylase. In addition to its effects on nitrogen metabolism, azatryptophan also affected carbon metabolism by inhibiting photosynthetic carbon assimilation and photosynthetic oxygen evolution. PMID- 2880835 TI - Enterobacterial fimbriae. PMID- 2880837 TI - ECT as a treatment alternative for patients with symptoms of neuroleptic malignant syndrome. AB - The use of ECT as a treatment alternative in a clinical situation in which it is difficult to determine whether the patient is suffering from neuroleptic malignant syndrome (NMS) or an evolving catatonic state is investigated. Fourteen cases from the literature are reviewed and 3 new cases are presented. In 6 cases, ECT was rapidly effective in treating symptoms of NMS, but cardiac arrhythmias were reported in 4 cases. There was no evidence of malignant hyperthermia (MH) in patients receiving succinylcholine, suggesting that an association between NMS and MH may not be clinically relevant in patients being treated with ECT. PMID- 2880838 TI - Aggressive behavior in Huntington's disease: treatment with propranolol. AB - Episodic aggressive behavior that responded poorly to neuroleptics was reduced by a carefully titrated dose of propranolol in three patients with advanced Huntington's disease. The optimal doses were 180, 30, and 30 mg/day, respectively. PMID- 2880836 TI - Regulation of nitrogenase activity by oxygen in Azospirillum brasilense and Azospirillum lipoferum. AB - The nitrogenase activity of the microaerophilic bacteria Azospirillum brasilense and A. lipoferum was completely inhibited by 2.0 kPa of oxygen (approximately 0.02 atm of O2) in equilibrium with the solution. The activity could be partially recovered at optimal oxygen concentrations of 0.2 kPa. In contrast to the NH4+ switch off, no covalent modification of the nitrogenase reductase (Fe protein) was involved, as demonstrated by Western-blotting and 32P-labeling experiments. However, the inhibition of the nitrogenase activity under anaerobic conditions was correlated with covalent modification of the Fe protein. In contrast to the NH4+ switch off, no increase in the cellular glutamine pool and no modification of the glutamine synthetase occurred under anaerobic switch-off conditions. Therefore, a redox signal, independent of the nitrogen control of the cell, may trigger the covalent modification of the nitrogenase reductase of A. brasilense and A. lipoferum. PMID- 2880839 TI - Comparative efficacy of long-acting depot and oral neuroleptic medications in preventing schizophrenic recidivism. AB - Two health service data bases provided data on the use of neuroleptic medications in the maintenance therapy of schizophrenic patients in the Canadian province of Saskatchewan. The pattern of prescribing medication appeared to be influenced by the bed-to-population ratio. For 1235 discharged schizophrenic patients, the 2 year rehospitalization rate (56%) was higher than expected. Although oral maintenance therapy predominated, patients maintained on long-acting depot neuroleptic medication had a significantly lower (p less than .05) rehospitalization rate than those on oral preparations. The highest rehospitalization rate was found among patients prescribed combined depot and oral preparations, confirming the ineffectiveness of combined medication. Using data bases avoided the sampling bias inherent in prospective controlled trials and provided a complementary epidemiologic dimension to the study of maintenance neuroleptic therapy of schizophrenia under normal treatment conditions. PMID- 2880840 TI - Effects of unsaturated fatty acids on the peroxisomal enzyme activities of Tetrahymena pyriformis. AB - The effects of unsaturated fatty acids on the activities of peroxisomal enzymes of Tetrahymena pyriformis were investigated. When saturated fatty acids and the corresponding unsaturated fatty acids (C18) were added to the culture medium at 0.05%, the activities of peroxisomal enzymes [fatty acyl-CoA oxidase (FAO), carnitine acetyltransferase (CAT), isocitrate lyase (ICL), and malate synthase (MS)] were significantly increased. The order of effectiveness was linoleic acid greater than oleic acid greater than stearic acid. However, alpha-linolenic acid and gamma-linolenic acid at the same concentration were lethal to the cells. The inhibitory effect on growth disappeared upon addition of an antioxidant, alpha tocopherol. Lipid peroxides derived from unsaturated fatty acids induced marked cell lysis. In the presence of a low concentration (0.005%) of linolenic acid the production of lipid peroxide was lower and no inhibitory effect on the growth was observed, while the activities of peroxisomal enzymes participating in lipid metabolism and that of catalase were significantly increased. These results indicate that the peroxisomal enzyme systems related to the beta-oxidations of fatty acids and the glyoxylate cycle are regulated by unsaturated long-chain fatty acids, including linolenic acid, at low concentrations, as well as by saturated fatty acid in the medium. PMID- 2880842 TI - Purification of a protease from Escherichia coli with specificity for oxidized glutamine synthetase. AB - A soluble Escherichia coli protease has been identified and purified to homogeneity. The protease cleaves glutamine synthetase which has been modified by mixed function oxidation; native glutamine synthetase is not a substrate. Using [14C]glutamine synthetase as a substrate (prepared by growing E. coli on 14C labeled amino acids), protease activity was assayed by determining the release of trichloroacetic acid-soluble material. The pure protease cleaves glutamine synthetase near the carboxyl terminus yielding 4,500 and 47,000 Mr products. The characteristics of this enzyme distinguish it from proteases previously purified from E. coli. These characteristics include a molecular weight of 75,000, alkaline pH optimum, lack of inhibition by serine protease inhibitors, and the ability to degrade insulin and casein. Oxidation of glutamine synthetase and other enzymes can be catalyzed by a variety of mixed function oxidase systems from bacterial and mammalian sources. Mixed function oxidation may be a "signal" or "marker" which consigns a protein for proteolytic degradation. Susceptibility to oxidation is subject to metabolic regulation, thereby providing control of proteolytic turnover. Isolation of a protease specific for modified glutamine synthetase provides the enzymatic basis for the specificity of this scheme. PMID- 2880841 TI - Stable structure of thermophilic proton ATPase beta subunit. AB - F1-ATPase is the major enzyme for ATP synthesis in mitochondria, chloroplasts, and bacterial plasma membranes. F1-ATPase obtained from thermophilic bacterium PS3 (TF1) is the only ATPase which can be reconstituted from its primary structure. Its beta subunit constitutes the catalytic site, and is capable of forming hybrid F1's with E. coli alpha and gamma subunits. Since the stability of TF1 resides in its primary structure, we cloned a gene coding for TF1, and the primary structure of the beta subunit was deduced from the nucleotide sequence of the gene to compare the sequence with those of beta's of three major categories of F1's; prokaryotic membranes, chloroplasts, and mitochondria. The following results were obtained. Homology: The primary structure of the TF1 beta subunit (473 residues, Mr = 51,995.6) showed 89.3% homology with 270 residues which are identical in the beta subunits from human mitochondria, spinach chloroplasts, and E. coli. It contained regions homologous to several nucleotide-binding proteins. Secondary structure: The deduced alpha-helical (30.1%) and beta-sheet (22.3%) contents were consistent with those determined from the circular dichroism spectra. Residues forming reverse turns (Gly and Pro) were highly conserved among the F1 beta subunits. Substituted residues and stability of TF1: We compared the amino acid sequence of the TF1 beta subunit with those of the other F1 beta subunits mentioned above. The observed substitutions in the thermophilic subunit increased its propensities to form secondary structures, and its external polarity to form tertiary structure. Codon usage: The codon usage of the TF1 beta gene was found to be unique. The changes in codons that achieved these amino acid substitutions were much larger than those caused by minimal mutations, and the third letters of the optimal codons were either guanine or cytosine, except in codons for Gln, Lys, and Glu. PMID- 2880843 TI - Catalytic properties of the F1-adenosine triphosphatase from Escherichia coli K 12 and its genetic variants as revealed by 18O exchanges. AB - We have examined intermediate Pi-water oxygen exchange during [gamma-18O]ATP hydrolysis by the F1 adenosine triphosphatase from Escherichia coli K-12. Water oxygen incorporation into each Pi released was increased as ATP concentration was lowered as observed previously for the same reaction catalyzed by the enzyme from eukaryotic sources. Heterogeneous distributions of 18O in product Pi were produced by coexisting epsilon subunit-replete and epsilon subunit-depleted enzyme molecules. The epsilon-replete enzyme showed a much higher probability for oxygen exchange. These data imply that the epsilon subunit inhibits net ATP hydrolysis by imposing conformational constraints which reduce the cooperative conformational interactions that promote ADP and Pi release. Four enzyme variants altered in alpha or beta subunit structure with reduced net hydrolytic activity showed sharply increased oxygen exchange during ATP hydrolysis. Heterogeneity was apparent in the 18O distribution of the product Pi, however. That behavior could reflect hindered conformational interactions and/or increased affinity of the alpha 3 beta 3 gamma delta complex for the epsilon subunit. In contrast, enzyme from mutant uncA401 showed very little oxygen exchange accompanying hydrolysis of 20 microM ATP. This is the only enzyme so far reported with this unusual property. Its rate limitation appears to be in the hydrolytic rather than the product release step of the catalytic sequence. PMID- 2880844 TI - Adaptation of skeletal muscle to increased contractile activity. Expression nuclear genes encoding mitochondrial proteins. AB - An increase in mitochondrial biogenesis in mammalian cells requires a coordinated increase in the expression of a number of nuclear genes that encode mitochondrial proteins. To examine the regulatory mechanisms involved, we used specific anti sense RNA probes to estimate the cellular concentrations of mRNA transcripts of two such nuclear genes in rabbit tibialis anterior muscles subjected in vivo to 10-21 days of indirect electrical stimulation. The unstimulated contralateral muscle in the same animals provided a base line for comparison. Change in expression of mitochondrial proteins was assessed in terms of the enzymatic capacity of citrate synthase and cytochrome oxidase, which increased 2.1-fold after 10 days and 5.5- and 4.1-fold, respectively, after 21 days of stimulation. As a proportion of total cellular RNA, messenger RNA encoding subunit beta of F1 ATPase increased 2.2-fold over control levels after 10 days and 2.3-fold after 21 days; mRNA encoding subunit VIC of cytochrome oxidase increased 1.3-fold and 1.9 fold over control levels after stimulation for 10 and 21 days, respectively. These changes were not attributable to nonspecific effects of stimulation on all mRNA transcripts, since aldolase A mRNA decreased to 26% of control levels after 21 days of stimulation. Furthermore, mRNA transcripts from these nuclear genes encoding mitochondrial proteins did not increase to the same extent as mRNA transcripts of mitochondrial genes such as cytochrome b, which increased 5.9-fold after 21 days of stimulation. We conclude that the increase in mitochondrial biogenesis induced by electrical stimulation of skeletal muscle is supported by pretranslational regulation of expression of nuclear genes encoding mitochondrial proteins. There are, however, indications that translational or post translational regulatory events may also be involved. PMID- 2880845 TI - Studies of the mechanism of glutamine synthetase utilizing pH-dependent behavior in catalysis and binding. AB - The pKa values of enzyme groups of Escherichia coli glutamine synthetase which affect catalysis and/or substrate binding were determined by measuring the pH dependence of Vmax and V/K. Analysis of these data revealed that two enzyme groups are required for catalysis with apparent pKa values of approximately 7.1 and 8.2. The binding of ATP is essentially independent of pH in the range studied while the substrate ammonia must be deprotonated for the catalytic reaction. Using methylamine and hydroxylamine in place of ammonia, the pKa value of the deprotonated amine substrate as expressed in the V/K profiles was shifted to a lower pKa value for hydroxylamine and a higher pKa value for methylamine. These data indicate that the amine substrate must be deprotonated for binding. Hydroxylamine is at least as good a substrate as ammonia judged by the kinetic parameters whereas methylamine is a poor substrate as expressed in both the V and V/K values. Glutamate binding was determined by monitoring fluorescence changes of the enzyme and the data indicate that a protonated residue (pKa = 8.3 +/- 0.2) is required for glutamate binding. Chemical modification by reductive methylation with HCHO indicated that the group involved in glutamate binding most likely is a lysine residue. In addition, the Ki value for the transition state analog, L-3 amino-3-carboxy-propanesulfonamide was measured as a function of pH and the results indicate that an enzyme residue must be protonated (pKa = 8.2 +/- 0.1) to assist in binding. A mechanism for the reaction catalyzed by glutamine synthetase is proposed from the kinetic data acquired herein. A salt bridge is formed between the gamma-phosphate group of ATP and an enzyme group prior to attack by the gamma-carboxyl of glutamate on ATP to form gamma-glutamyl phosphate. The amine substrate subsequently attacks gamma-glutamyl phosphate resulting in formation of the tetrahedral adduct before phosphate release. A base on the enzyme assists in the deprotonation of ammonia during its attack on gamma glutamyl phosphate or after the protonated carbinol amine is formed. Based on the kinetic data with the three amine substrates, catalysis is not rate-limiting through the pH range 6-9. PMID- 2880846 TI - A mutation of the c subunit of the Escherichia coli proton-translocating ATPase that suppresses the effects of a mutant b subunit. AB - A mutation of the b subunit of the Escherichia coli proton-translocating ATPase and mutations in the gene for the a subunit that suppress its effects have been previously described (Kumamoto, C., and Simoni, R. D. (1986) J. Biol. Chem. 261, 10037-10042). In this paper, we describe the characterization of a new mutation that partially suppresses the effects of the original b mutation. The new suppressor mutation causes the substitution of serine for alanine at position 62 of the c subunit. Biochemical studies of double mutants, carrying both b and c mutations, demonstrate that the c mutation partially restores the function of the enzyme complex. PMID- 2880847 TI - Lecithin:cholesterol acyltransferase. Functional regions and a structural model of the enzyme. AB - The amino acid sequence of human lecithin:cholesterol acyltransferase has been determined by degradation and alignment of peptides obtained from tryptic and staphylococcal digestions and the cleavage with cyanogen bromide and consisted of 416 amino acid residues. All of the tryptic peptides of lecithin:cholesterol acyltransferase were isolated and sequenced. Peptides resulting from digestion by staphylococcal protease, cyanogen bromide cleavage, or the combination of the two methods were employed to find overlapping segments. The N terminus of human lecithin:cholesterol acyltransferase was determined to be phenylalanine by sequencing the whole protein up to 40 residues while the C terminus was identified as glutamic acid through carboxypeptidase Y cleavage. Cys50 and Cys74 and Cys313 and Cys356 were identified as the two disulfide bridges while the free sulfhydryl groups were located at positions 31 and 184. The N-glycosylated sites of the protein were assigned to asparagines at positions 20, 84, 272, and 384. The active site of lecithin:cholesterol acyltransferase was identified as serine on position 181 according to its homology with other serine-type esterases which have a common structure of glycine-variable amino acid-active serine-variable amino acid-glycine (Gly-X-Ser-X-Gly) with the variable amino acids disrupting the homology. No long internal repeats or homologies with apolipoproteins were found. The secondary structure is consistent with the results of predictive algorithms. A simple model of the enzyme is proposed on the basis of available chemical data and predictive methods. PMID- 2880848 TI - Study of the nucleotide binding site of the yeast Schizosaccharomyces pombe plasma membrane H+-ATPase using formycin triphosphate-terbium complex. AB - The plasma membrane of yeasts contains an H+-ATPase similar to the other cation transport ATPases of eukaryotic organisms. This enzyme has been purified and shows H+ transport in reconstituted vesicles. In the presence of Mg2+, formycin triphosphate (FTP) is hydrolyzed by the H+-ATPase and supports H+ transport. When combined with terbium ion, FTP (Tb-FTP) and ATP (Tb-ATP) are no longer hydrolyzed. Competition between Mg-ATP and Tb-FTP for ATP hydrolysis indicates that terbium-associated nucleotides bind to the catalytic site of the H+-ATPase. The fluorescent properties of the Tb-FTP complex were used to study the active site of the H+-ATPase. Fluorescence of Tb-FTP is greatly enhanced upon binding into the nucleotide site of H+-ATPase with a dissociation constant of 1 microM. Tb-ATP, Tb-ADP, and Tb-ITP are competitive inhibitors of Tb-FTP binding with Ki = 4.5, 5.0, and 6.0 microM, respectively. Binding of Tb-FTP is observed only in the presence of an excess of Tb3+ with an activation constant Ka = 25 microM for Tb3+. Analysis of the data reveals that the sites for Tb-FTP and Tb3+ binding are independent entities. In standard conditions these sites would be occupied by Mg ATP and Mg2+, respectively. These findings suggest an important regulatory role of divalent cations on the activity of H+-ATPase. Replacement of H2O by D2O in the medium suggests the existence of two types of nucleotide binding sites differing by the hydration state of the Tb3+ ion in the bound Tb-FTP complex. PMID- 2880849 TI - Modulation of microtubule assembly and stability by phosphatidylinositol action on microtubule-associated protein-2. AB - Exposure of elongating (or assembled) bovine brain microtubules to phosphatidylinositol leads to polymerization arrest (or disassembly). The efficiency of phosphatidylinositol far exceeds the action of related phospholipids including phosphatidylethanolamine, phosphatidylcholine, 1,2 diacylglycerol, phosphatidylserine, phosphatidylglycerol, or phosphatidic acid. Phosphatidylinositol increases the apparent critical concentration for assembly, and the inhibitory effect of phosphatidylinositol on polymerization is reversed at higher concentrations of microtubule-associated proteins (MAP)s. Taxol- and glycerol-treated microtubules are insensitive to the destabilizing action of phosphatidylinositol; centrifugation and subsequent gel electrophoresis of such samples revealed that both MAP-2a and MAP-2b were selectively desorbed. Likewise, the desorption of MAP-2 was visualized by indirect immunofluorescence microscopy using primary antibodies directed toward tubulin and MAP-2. The instability of microtubules exposed to phosphatidylinositol appears to be related to the MAP-2 content. PMID- 2880850 TI - Adenine nucleotide binding sites on beef heart F1-ATPase. Asymmetry and subunit location. AB - Previously we have shown that beef heart mitochondrial F1 contains a total of six adenine nucleotide binding sites. Three "catalytic" sites exchange bound ligand rapidly during hydrolysis of MgATP, whereas three "noncatalytic" sites do not. The noncatalytic sites behave asymmetrically in that a single site releases bound ligand upon precipitation of F1 with ammonium sulfate. In the present study, we find this same site to be the only noncatalytic site that undergoes rapid exchange of bound ligand when F1 is incubated in the presence of EDTA at pH 8.0. Following 1000 catalytic turnovers/F1, the site retains the unique capacity for EDTA-induced exchange, indicating that the asymmetric determinants are permanent and that the three noncatalytic sites on soluble F1 do not pass through equivalent states during catalysis. Measurements of the rate of ligand binding at the unique noncatalytic site show that uncomplexed nucleotide binds preferentially. At pH 7.5, in the presence of Mg2+, the rate constant for ADP binding is 9 X 10(3) M-1 s-1 and for dissociation is 4 X 10(-4) s-1 to give a Kd = 50 nM. The rate of dissociation is 10 times faster in the presence of EDTA or during MgATP hydrolysis, and it increases rapidly at pH below 7. EDTA-induced exchange is inhibited by Mg2+, Mn2+, Co2+, and Zn2+ but not by Ca2+ and is unaffected by dicyclohexylcarbodiimide modification. The unique noncatalytic site binds 2-azido-ADP. Photolysis results in the labeling of the beta subunit. Photolabeling of a single high-affinity catalytic site under conditions for uni site catalysis also results in the labeling of beta, but a different pattern of labeled peptides is obtained in proteolytic digests. The results demonstrate the presence of two different nucleotide binding domains on the beta subunit of mitochondrial F1. PMID- 2880852 TI - Evidence for medetomidine as a selective and potent agonist at alpha 2 adrenoreceptors. AB - The activity on alpha-adrenoreceptors of medetomidine ((+/-)-4-(alpha,2,3 trimethylbenzyl)imidazole), an alpha-methyl derivative of detomidine, has been characterized in vivo and in vitro using detomidine, MPV 207, MPV 295, azepexole, clonidine and xylazine for reference purposes. Medetomidine (1-100 micrograms/kg i.v.) was a hypotensive and bradycardic compound in anaesthetized rats. Furthermore, it induced vasopressor (PD50 1.7 microgram/kg) and sympatho inhibitory (ID50 1.6 microgram/kg) actions in pithed rats, the effects being antagonized by idazoxan (0.3 mg/kg i.v.) but not by prazosin (0.1 mg/kg i.v.). Medetomidine (30-300 micrograms/kg i.m.) had an alpha 2-adrenoreceptor mediated sedative effect on chicks. Medetomidine was, overall, more potent than detomidine, MPV 207, clonidine, xylazine, MPV 295 or azepexole in central (sedation in the chick) and peripheral (cardiac presynaptic in the pithed rat) actions on alpha 2-adrenoreceptors. Clonidine had, however, about an equal potency to medetomidine in the vascular smooth muscle of the pithed rat. Like detomidine and MPV 295, medetomidine had no agonistic activity in the rat aortic ring, but high concentrations antagonized methoxamine-induced contractions, giving a pA2 value of 5.68 for alpha 1-adrenoreceptor antagonism. The overall lipophilicity (log P') of medetomidine in the octanol/buffer (pH 7.4, 24-26 degrees C, HPLC technique) was 2.80. In summary, the experimental data suggest that medetomidine is a lipophilic compound with selective alpha 2-adrenoreceptor stimulating properties and high potency. It may, therefore, prove to be a suitable pharmacologic tool for interventions in alpha 2-adrenoreceptor mediated effects in the autonomic nervous system. PMID- 2880851 TI - The clathrin coat assembly polypeptide complex. Autophosphorylation and assembly activities. AB - A 50-kDa polypeptide that is rapidly phosphorylated on addition of [gamma-32P]ATP to isolated clathrin-coated vesicles is shown here to be identical to the 50-kDa component (AP50) of the clathrin assembly protein (AP), a complex that promotes the assembly of clathrin coat structures under physiological conditions of pH and ionic strength. Phosphorylation of the AP50 occurred readily at 0 degrees C, almost exclusively on a threonyl residue(s). This reaction is attributable to autophosphorylation, since the AP50 was able to covalently incorporate 32P from [gamma-32P]ATP after separation by either one- or two-dimensional sodium dodecyl sulfate gel electrophoresis. Kinetic studies in solution were consistent with an intramolecular phosphorylation event; in addition, a concentration-dependent increase in AP50 phosphorylation was observed that may reflect intermolecular AP AP activation of autophosphorylation. The phosphorylated AP50 was resistant to several inorganic phosphatases tested but was a substrate for protein phosphatases 1 and 2A, suggesting that a physiological phosphorylation dephosphorylation cycle may exist. The phosphorylation state of the AP50 did not affect the ability of the AP to promote in vitro clathrin coat assembly. These and other data suggest that unique structural domains of the assembly protein are responsible for assembly (the 100-kDa components) and autophosphorylation (the AP50) and that the latter may be active as a protein kinase in the intact cell. PMID- 2880854 TI - The effect of beta-adrenoreceptor antagonists on the inhibition of pendular movements of rabbit ileum produced by periarterial sympathetic nerve stimulation and some sympathomimetic amines. AB - The effects of propranolol and of the selective beta 1- and beta 2-adrenoreceptor blocking drugs atenolol and ICI 118,551 were determined on the inhibitory responses of isolated segments of rabbit ileum to noradrenaline, isoprenaline and salbutamol and to periarterial sympathetic nerve stimulation. Responses to isoprenaline (0.04-10.24 microM) and salbutamol (1.4-89.6 microM) were blocked by propranolol in concentrations up to 5.0 and 12.8 microM, respectively. Responses to sympathetic nerve stimulation were reduced but responses to noradrenaline (0.03-1.92 microM) were unaffected by propranolol in concentrations up to 10.0 and 5.0 microM, respectively. Atenolol in concentrations up to 30.0 microM blocked responses to isoprenaline (0.04-2.56 microM) but did not affect responses to noradrenaline, salbutamol or sympathetic nerve stimulation in concentrations up to 3.0, 3.0 and 1.0 microM, respectively. However, when responses to noradrenaline and sympathetic nerve stimulation were reduced by phentolamine (1.0 microM), atenolol then produced further reductions. Responses to isoprenaline (0.04-2.56 microM) and salbutamol (1.4-89.6 microM) were blocked by ICI 118,551 in concentrations up to 0.5 microM. Responses to sympathetic nerve stimulation were reduced but responses to noradrenaline were unaffected by ICI 118,551 in concentrations up to 0.01 and 0.3 microM, respectively. Salbutamol (0.1 microM) increased the inhibitory response to sympathetic nerve stimulation and this effect was blocked by ICI 118,551 (0.01 microM). It was concluded that blockade of beta 2-adrenoreceptors, presumably located on sympathetic nerve terminals, decreases the release of transmitter noradrenaline and that blockade of beta 1 adrenoreceptors, presumably located in longitudinal smooth muscle cells, reduces the response to transmitter noradrenaline when alpha-adrenoreceptors are also blocked. PMID- 2880853 TI - Positive chronotropic responses to cardiac alpha 1-adrenoreceptor activation in the pithed rat. AB - Adrenaline (0.1-10 micrograms/kg), noradrenaline (0.1-10 micrograms/kg) and phenylephrine (1-100 micrograms/kg) acted on both cardiac alpha 1- and beta adrenoreceptors to induce positive chronotropic responses in the pithed rat. When beta-adrenoreceptors were blocked by propranolol (1 mg/kg), the residual chronotropic responses were due to activation of alpha 1-adrenoreceptors since they were significantly reduced by prazosin (10-100 micrograms/kg). Methoxamine (10-300 micrograms/kg) acted solely on cardiac alpha 1-adrenoreceptors to induce positive chronotropic responses which were abolished by prazosin (10-100 micrograms/kg) alone, as has been demonstrated previously for amidephrine. The rank order of potency for eliciting the positive chronotropic response to alpha 1 adrenoreceptor activation was adrenaline greater than noradrenaline greater than phenylephrine greater than methoxamine. The positive chronotropic responses to adrenaline (3-10 micrograms/kg), noradrenaline (3-10 micrograms/kg) and phenylephrine (30-100 micrograms/kg) produced by activating alpha 1 adrenoreceptors had a slower time course than did the chronotropic responses produced by activation of beta-adrenoreceptors. PMID- 2880855 TI - Rapid and sensitive determination of ethotoin as well as carbamazepine, phenobarbital, phenytoin and primidone in human serum. PMID- 2880856 TI - Determination of metipranolol and desacetylmetipranolol in aqueous humor of rabbit eye by gas chromatography with electron-capture detection. PMID- 2880857 TI - Rapid and simple determination of alprenolol in serum. PMID- 2880858 TI - On-line low-level radiometric detection of [14C]remoxipride in liquid chromatographic effluents. Application to urine samples. AB - A method for on-line radiometric detection in liquid chromatography (LC) is described that permits the detection of low levels of radioactivity in LC effluents by using solvent segmentation and storage of the segmented effluent in a capillary storage loop. The object of the method is to make the flow-rate in the on-line radioactivity monitor (and hence the mean residence time in the monitor) independent of the separation process. Therefore, after storage of the complete chromatogram, the segmented effluent is led through the monitor at flow rates that can be chosen according to the residence time desired for accurate and precise radioactivity determination. In this system, it is possible to use a flow cell volume small enough to preserve the chromatographic integrity, while maintaining the possibility of increasing the counting time. Tests have been performed on the reproducibility of 14C detection and the influence of the flow rate through the monitor on the standard deviation in 14C peak area and, thus, on the detection limit, using 14C-labelled remoxipride. As an application, analyses of urine samples for [14C]remoxipride and one of its potential metabolites are reported. PMID- 2880859 TI - Determination of falintolol, a new aliphatic beta-adrenergic antagonist, in whole blood by gas chromatography with electron-capture detection: geometric isomers resolution. AB - Falintolol oxalate, a new beta-adrenergic antagonist, is characterized by the presence of an oxime function and exists in a racemic form as a mixture of syn- and anti- isomers in a ratio of about 8:2. This article describes a selective gas chromatographic method for the resolution of the geometric isomers and the quantitation of the drug. The unchanged falintolol and internal standard, a related compound, are separated from blood by a solvent extraction under alkaline conditions, and then the drug is derivatized. The heptafluorobutyric derivatives are chromatographed on an SE-30 capillary quartz column and detected with a nickel-63 electron-capture detector. Because the syn- and anti- isomers of falintolol display comparable chromatographic responses, the sum of the two geometrical isomers is used for the quantitation of falintolol in blood. This method allows small serial blood samples in conscious rats, and 0.05 microgram of falintolol/0.1 mL of blood can be routinely determined. A calibration curve is prepared for the blood extracts. Linearity is observed in the study range (0.05 to 1 microgram/0.1 mL of blood). No interference by endogenous substances is observed. The procedure is applied successfully to drug absorption in rats when repeated oral doses are administered. PMID- 2880860 TI - Use of [3H]cortivazol to characterize glucocorticoid receptors in a dexamethasone resistant human leukemic cell line. AB - ICR 27 is a mutant derived from the glucocorticoid-sensitive human leukemic cell line CEM C7 that has been characterized as glucocorticoid receptor negative based on its ability to specifically bind [3H]dexamethasone ([3H]DEX). We used the pyrazolosteroid [3H]cortivazol ([3H]CVZ) to determine whether ICR 27 cells actually contain glucocorticoid receptors and, if so, whether these receptors can mediate physiological effects. Scatchard analysis of the binding of [3H]CVZ to cytosol from ICR 27 cells was consistent with a single class of receptors of uniform affinity (0.7 nM). Cytosolic [3H]CVZ complexes had a sedimentation coefficient of 4.6S on linear sucrose gradients and eluted from DEAE-cellulose columns at a potassium phosphate concentration of 250 mM. CVZ also competed with [3H]DEX mesylate for binding to a 96,000 mol wt protein. Incubation of ICR 27 cells with CVZ caused 50% growth inhibition and 50% maximal induction of glutamine synthetase activity at concentrations of 20 and 35 nM, respectively. Elution profiles of [3H]CVZ complexes from DEAE-cellulose columns showed that complexes formed upon thermal activation were relatively unstable, and little or no increase in binding of [3H]CVZ-receptor complexes to DNA-cellulose was observed. Thus, [3H]CVZ identifies functional glucocorticoid receptors in a cell line previously described as DEX resistant. Although the binding of [3H]CVZ to activated receptors in vitro appears unstable, high concentrations of CVZ may facilitate stabilization of activated complexes that can mediate both anabolic and catabolic effects. PMID- 2880861 TI - Medical treatment of acromegaly with SMS 201-995, a somatostatin analog: a comparison with bromocriptine. AB - We studied the effects of acute and chronic sc administration of SMS 201-995 (SMS), a long-acting somatostatin analog, in acromegalic patients. The results were compared with those obtained in the same patients treated with oral bromocriptine (Brc). A single dose of 50 micrograms SMS administered to 28 patients induced a more rapid, greater, and more prolonged reduction in plasma GH levels than did 2.5 mg Brc. Chronic treatment [60-330 days; mean 208 +/- 23 (+/- SEM)] with SMS (100-300 micrograms/day) induced in 16 patients a significantly greater decrease in mean plasma GH and somatomedin-C levels than did 20 mg Brc. Combined treatment with the 2 agents had an additional effect. The clinical and metabolic parameters of acromegaly dramatically improved in all patients whose plasma GH and somatomedin-C levels decreased even if they were not normalized by SMS. Reduction in tumor size occurred in 3 of the 10 patients examined by computed tomography before and during SMS treatment. We conclude that SMS is more effective than Brc and that the 2 drugs may be complementary in the medical treatment of acromegaly. PMID- 2880862 TI - Differences in the opioid control of luteinizing hormone secretion between pathological and iatrogenic hyperprolactinemic states. AB - The cause of the amenorrhea that occurs in patients with hyperprolactinemia is unknown. The involvement of endogenous opioid peptides in the inhibition of GnRH release as a central factor leading to the hypogonadotropic state has been recently described. This study analyzed the LH response to opiate receptor blockade by naloxone (4 mg, iv) in groups of subjects with amenorrhea due to hyperprolactinemia of different etiologies. Patients presenting with a PRL secreting pituitary adenoma (n = 7), idiopathic hyperprolactinemia (n = 9), or hyperprolactinemia during pharmacological treatment for schizophrenia (n = 5) were studied. Furthermore, to evaluate whether high circulating PRL levels influence the activity of the opioid system after the menopause, a group of seven postmenopausal subjects was tested before and 1 week after the administration of metoclopramide (10 mg, three times a day), a dopamine receptor antagonist. Normal premenopausal women (n = 6) served as controls. Naloxone significantly increased plasma LH levels in both prolactinoma and idiopathic hyperprolactinemic patients (P less than 0.01 vs. basal and placebo). In neither of those groups was a significant correlation found between the plasma LH response to naloxone and basal plasma PRL levels. In contrast to pathological hyperprolactinemia, blockade of opiate receptors did not significantly change LH secretion in either amenorrheic women with pharmacologically induced hyperprolactinemia or postmenopausal women. These results suggest that the effect of hyperprolactinemia on opioid modulation of LH secretion is related to the nature of the hyperprolactinemic state, supporting the existence of increased opioid inhibition of LH levels in pathological hyperprolactinemia. PMID- 2880863 TI - Phorbol ester and phospholipase C-induced growth hormone secretion from pituitary somatotroph adenoma cells in culture: effects of somatostatin, bromocriptine, and pertussis toxin. AB - To clarify the role of the breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2) in GH secretion in human somatotrophs and the effects of inhibitors of GH secretion on this mechanism, we studied the effects of 12-tetradecanoylphorbol-13 acetate (TPA) and phospholipase C (Plase C) on GH secretion and the interactions of somatostatin (SRIH), bromocriptine, and pertussis toxin (IAP) with TPA or Plase C, using human GH-secreting pituitary adenoma cells in culture. SRIH (10( 9)-10(-7) M) inhibited and TPA (10(-10)-10(-8) M) and Plase C (0.125-1.0 U/mL) stimulated GH secretion. SRIH (10(-9)-10(-7) M) inhibited GH release induced by TPA (10(-8) M) or Plase C (1.0 U/mL). Bromocriptine (10(-8) M) also inhibited 10( 8) M TPA-induced GH secretion. When adenoma cells were treated with 100 ng/mL IAP for 24 h, basal and TPA-induced GH secretion rates did not change. However, the inhibitory effects of SRIH (10(-8) M) or bromocriptine (10(-8) M) on basal and 10(-8) M TPA-stimulated GH secretion were attenuated. In addition, IAP reduced GH secretion induced by 0.5 U/mL Plase C, while SRIH inhibition of Plase C-evoked GH release was diminished by IAP. We conclude that the hydrolysis of PIP2 by Plase C, which causes activation of protein kinase C by 1,2-diacylglycerol and Ca2+ mobilization by inositol 1,4,5-triphosphate, is a physiological intracellular mechanism leading to GH secretion in human somatotrophs; SRIH inhibits GH secretion mediated by this mechanism, and bromocriptine blocks at least protein kinase C-mediated GH release; the inhibitory guanine nucleotide-binding protein (Ni) is involved in these inhibitory effects of SRIH and bromocriptine; and Ni modulates the breakdown of PIP2 by Plase C. PMID- 2880865 TI - Intrathyroidal T cell clones from patients with autoimmune thyroid disease. AB - We cloned activated T cells from thyroid tissue of patients with autoimmune thyroid disease. After separation on 40% Percoll gradients, T cells were cultured for 2-7 days with T cell growth factor (interleukin 2; 20 U/mL) and cloned by limiting dilution (0.3 cells/well) in the presence of irradiated autologous peripheral blood mononuclear cells (PMC; 10,000/well) as feeder cells. Fifty seven clones were successfully expanded and tested for reactivity, cytotoxicity, helper/suppressor function, and phenotype. In the reactivity assays clones were tested for responses to autologous and allogeneic PMC, thyroid cells, human thyroglobulin (hTg), and microsomal antigen. Two distinct patterns of functional T cell clones emerged from these characterization studies. Seventy-five percent of T cell clones recovered from Graves' disease thyroid tissue (n = 21) were of helper-induced (CD4+/4B4+) phenotype, and most were effective immunoglobulin helper clones. Fifty percent of Graves' T cell clones responded to autologous PMC, and 33% had a proliferative response to autologous thyroid cells. No cytotoxic clones were derived from Graves' thyroid tissue. By contrast, intrathyroidal T cell clones from patients with autoimmune thyroiditis (n = 36) were 59% suppressor/cytotoxic (CD8+) phenotype, 17% suppressed immunoglobulin secretion, and 55% were cytotoxic to allogeneic blast cells. Fifty-five percent of clones also responded to autologous PMC, and one clone was nonspecifically autocytotoxic. In the thyroid antigen proliferation assays 11% of thyroiditis clones reacted to human thyroglobulin, but none responded to microsomal antigen. Two clones were cytotoxic to autologous but not allogeneic thyroid cells. These data demonstrate that the majority of intrathyroidal T cells in autoimmune thyroid disease are autoreactive. However, small numbers of thyroid-specific T cell clones are present within the thyroid of such patients; they are principally helper-inducer T cells in Graves' disease thyroid and cytotoxic T cells in autoimmune thyroiditis. PMID- 2880864 TI - Diurnal patterns of pulsatile luteinizing hormone secretion in hypothalamic amenorrhea: reproducibility and responses to opiate blockade and an alpha 2 adrenergic agonist. AB - The pattern of pulsatile GnRH secretion is abnormal in some women with hypothalamic amenorrhea (HA) consequent to previous exercise or weight loss. Both diminished frequency pulsatile LH secretion, and by inference GnRH secretion, and normal LH pulsatility have been reported. We assessed whether the patterns of GnRH secretion varied with time by measuring plasma LH every 15 or 20 min for 24 h on 1-3 occasions during a 10-month period in 14 women with HA (a total of 24 studies). During the day, mean LH pulse frequency [1.0 +/- 0.1 (+/- SE) pulses/8 h] was lower than that in normal women in the early follicular phase of their cycles (5.1 +/- 0.6), and the frequency in individual HA patients was lower than early follicular phase values in 16 of 17 studies. The slow daytime LH pulse frequency also was a consistent finding, in that the values in repeat studies varied by less than 2 pulses/8 h in all but 1 patient. LH pulse frequency (2.0 +/ 0.4 pulses/8 h) was higher and more variable during sleep, and normal early follicular phase frequencies were found in 20% of patients with HA. The mechanisms whereby GnRH pulse frequency is reduced are not known. alpha Adrenergic agonist drugs stimulate GnRH pulsatile secretion in rodents, but administration of the alpha 2-agonist clonidine (0.15 mg, orally, at 0800 and 2000 h) did not increase the frequency of LH pulses in 7 women (1.7 +/- 0.4 pulses/8 h). In contrast, administration of naloxone (1 mg/m2 X h, iv) for 8 h during the day to 14 patients, increased LH pulse frequency (3.3 +/- 0.5 pulses/8 h). In 8 of these 14 women, LH pulse frequency (4.9 +/- 0.4 pulses/8 h) increased into the range found during the normal early follicular phase, while in the other 6 women pulse frequency was not significantly increased (1.4 +/- 0.4 pulses/8 h). Plasma estradiol levels were similar in naloxone-responsive and unresponsive women, but spontaneous LH pulse frequency was higher at night in naloxone responsive patients (2.9 +/- 0.6 vs. 1.4 +/- 0.3 pulses/8 h). The presence of nocturnal LH pulses did not predict responsiveness to naloxone, however, and LH pulse frequency was less than 2 pulses/8 h in 4 of the women who responded to naloxone. These data indicate that slow frequency GnRH secretion is a common finding during the day in women with HA. GnRH secretion is more variable at night, suggesting that the mechanisms involved in reducing pulsatile GnRH secretion are less effective during sleep.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2880867 TI - Receptor-specific agglutination tests for detection of bacteria that bind globoseries glycolipids. AB - Specific binding to the globoseries of glycolipid receptors explains the adherence of uropathogenic Escherichia coli to host cells. The minimal receptor disaccharide Gal alpha 1----4Gal beta [galactose alpha (1----4)galactose beta] is recognized by most attaching clinical isolates. However, wild-type isolates can express adhesins with several different receptor specificities. Bioassays do not permit separate analysis of each receptor specificity, since the target cells contain multiple potentially receptor-active molecules. In this study, bacterial adhesins were analyzed by using receptors immobilized into latex beads in one of two ways. In one way, di- and trisaccharides were covalently linked via a spacer arm to latex beads coupled with bovine serum albumin. In the other way, receptor active glycolipids were coated onto the bovine serum albumin-latex beads. The latex beads were subsequently used for agglutination by using type strains with known receptor specificity. The composition was optimized regarding receptor structure and size of latex beads. Gal alpha 1----4Gal beta was as active as the trisaccharide derivative Gal alpha 1----4Gal beta 1----3glucose or Gal alpha 1--- 4Gal beta 1----3glucosamine. Among the natural glycolipids tested, globotetraosylceramide was the most active. Subsequently, the sensitivity and specificity of the Gal alpha 1----4Gal beta-latex and globotetraosylceramide latex reagents were compared for 733 E. coli urinary isolates. Hemagglutination of human erythrocytes was used as the positive standard. No significant difference in the specificity or sensitivity of the latex reagents was found; the sensitivity ranged from 86%, when isolates agglutinating human erythrocytes of blood groups P1 and p were included, to 93%, when those isolates agglutinating erythrocytes of blood group p were excluded. These reagents provide tools for bacterial identification in patients with urinary tract infection. PMID- 2880866 TI - Monoclonal antibody passive hemagglutination and capture enzyme-linked immunosorbent assays for direct detection and quantitation of F41 and K99 fimbrial antigens in enterotoxigenic Escherichia coli. AB - Production of diarrhea in neonatal calves by enterotoxigenic Escherichia coli depends on its ability to attach to the epithelial cells of the intestine via surface adhesins called pili or fimbriae and to secrete enterotoxins. The most important of these fimbriae are designated K99 and F41. We produced and characterized a murine monoclonal antibody specific to F41. This monoclonal antibody and a K99-specific monoclonal antibody were used to develop sensitive and specific passive hemagglutination and capture enzyme-linked immunosorbent assays (ELISAs) for detection and quantitation of F41 and K99 antigens in E. coli cultures and culture supernatants. The capture ELISA systems exhibited excellent sensitivity and specificity, whereas the passive hemagglutination systems appeared to be oversensitive. The ability of the capture ELISAs to detect K99 and F41 fimbrial antigens in fecal specimens from calves was evaluated. Fimbrial antigens were detected in six of six specimens from scouring calves but not in four of four specimens from nonscouring calves. PMID- 2880868 TI - Binding to galactose alpha 1----4galactose beta-containing receptors as potential diagnostic tool in urinary tract infection. AB - The diagnosis of urinary tract infection is based largely on quantitative urine cultures. The usefulness of qualitative information about the virulence of the infecting bacteria remains undefined. Ability to attach to human uroepithelial cells is one characteristic of the pyelonephritogenic clones, as well as a virulence factor per se. The identification of host cell receptors for attaching bacteria has permitted the construction of agglutination tests for simple detection of bacterial binding properties. In the present study, the reactivity with Gal alpha 1----4Gal beta-latex [galactose alpha (1----4)galactose beta latex] and globotetraosylceramide-latex was analyzed for strains from patients with acute pyelonephritis (n = 135), acute cystitis (n = 121), and asymptomatic bacteriuria (n = 119) and from the fecal flora of healthy children (n = 120) and compared with agglutination of human blood group P1 and p, as well as guinea pig, erythrocytes. The reactivity by bioassay and the receptor-specific assays were significantly correlated. The frequency of positive reactions among the pyelonephritis isolates was 78.5% with the globotetraosylceramide-latex reagent, compared with 41% for the cystitis isolates, 25% for the asymptomatic bacteriuria isolates, and 13% for the fecal isolates. The combination of bioassays and receptor-specific assays increased the resolution of adhesins. Thus, adhesins reacting with human p erythrocytes frequently were coexpressed with Gal alpha 1-- -4Gal beta-specific adhesins. The receptor-specific assays provide a refined reagent to resolve bacterial binding specificities, as well as a potential tool for clinical diagnosis. PMID- 2880871 TI - Recent advances in pharmaceutical chemistry--review II. Histamine H2-receptor antagonists. AB - The concept of histamine receptors is outlined and the rationale for the synthesis of H2-antagonists presented. Structure-activity relationships among these compounds are described and aspects of absorption, distribution and elimination discussed with particular reference to cimetidine and ranitidine. Oxmetidine, lupitidine and loxtidine are also considered. Methods for the analysis of these drugs in body fluids are presented followed by a discussion of their toxicology. Volunteer and patient studies are also surveyed. PMID- 2880869 TI - Leukocytes from four patients with complete or partial Leu-CAM deficiency contain the common beta-subunit precursor and beta-subunit messenger RNA. AB - Deficiency of a family of three leukocyte adhesion molecules (Leu-CAM) is associated with recurrent and life-threatening bacterial infections in man. Each of the three antigens, Mo1, LFA-1, and Leu M5 has a distinct alpha subunit noncovalently associated with a common beta subunit that appears to be required for the expression of these antigens on the cell surface. To investigate the molecular basis of Leu-CAM deficiency, we studied leukocytes from four unrelated patients suffering from complete or partial Leu-CAM deficiency using immunoprecipitation of metabolically labeled proteins, RNA extraction, and Northern blot analysis. We found that B cells from all four patients synthesized a normal sized beta subunit precursor that either failed to "mature" or matured only partially to the membrane expressed form. B cells from all four patients also had a single normal sized beta subunit mRNA of approximately 3.4 kb. Leu-CAM deficiency, in these unrelated patients, is not due to the absence of the beta chain gene or to aberrant splicing of its mRNA and are consistent with a defective beta subunit gene resulting in abnormal posttranslational processing of the synthesized molecule. PMID- 2880873 TI - Gepirone in anxiety: a pilot study. AB - Ten patients suffering from generalized anxiety disorder were treated, after a single-blind placebo washout week, with the nonbenzodiazepine anxiolytic gepirone in a 6-week open label trial. Mean Hamilton Anxiety scores improved from 24.8 to 7.1 (p less than 0.01). Other physician- and patient-rated scales showed comparable improvement on a mean maximal dose of 41 mg of gepirone. The medication appeared to be nonsedating and well tolerated. The anxiolytic effect of the medication was very marked in several cases, and gepirone appears to have promise as an anxiolytic agent. PMID- 2880872 TI - A comparison of buspirone and placebo in relieving benzodiazepine withdrawal symptoms. AB - Buspirone is a new antianxiety compound of a totally new type which may avoid the dependence problems of its predecessors. This study was designed to evaluate any possible cross-tolerance to the benzodiazepines. Twenty-four outpatients on long term therapeutic dose benzodiazepine treatment, who wished to discontinue treatment, were allocated randomly to placebo substitution or buspirone substitution and then withdrawal over a total of 10 weeks. Assessments were made at weekly intervals. Of the 24 patients entered into the trial, 13 received buspirone and 11 placebo. Only five of the buspirone and six of the placebo patients successfully completed withdrawal. Some anxiolytic action of buspirone was detected, but it was insufficient to materially assist the withdrawal. No evidence was found that buspirone was cross-tolerant to the benzodiazepines. It was concluded that buspirone does not help benzodiazepine withdrawal and does not suppress benzodiazepine withdrawal symptoms. PMID- 2880870 TI - Stimulation of gastrin release by bombesin and canine gastrin-releasing peptides. Studies with isolated canine G cells in primary culture. AB - Bombesin, a polypeptide derived from frog skin, has been shown to stimulate gastrin release from the gastric antrum in vivo and in vitro. To elucidate the mechanisms of this effect, we developed a method to culture isolated and enriched G cells from canine stomach. After digestion of antral mucosa with collagenase and EDTA, dispersed cells were fractionated by counterflow elutriation then cultured on a collagen support. Bombesin and three molecular forms of canine gastrin-releasing peptides all stimulated gastrin release from G cells in a dose dependent manner. The effect of bombesin was suppressed by somatostatin and potentiated by dibutyryl cyclic AMP (10(-3) M) but not by carbachol (10(-6) M). Extracellular calcium depletion attenuated the stimulation of gastrin release by bombesin but not by forskolin. These findings suggest that the bombesin family peptides directly activate G cells through calcium-dependent mechanisms to cause gastrin release. PMID- 2880874 TI - Autism: the treatment of aggressive behaviors. AB - Eight consecutive cases of adults with the diagnosis of early infantile autism and who were treated with a betablocker are presented. Each had been on various and multiple drug, educational, and behavioral regimens to help control aggressive and self-abusive behavior. Most had been institutionalized from an early age, and a broad range of IQs and speech capacities are represented. Results show the betablockers to have a remarkable effect potentiating measurable diminution in previously intractable aggressive behavior and in many cases the decrease or withdrawal of their neuroleptic. PMID- 2880875 TI - A view from the Nation's courts. PMID- 2880876 TI - Wernicke-Korsakoff's syndrome and the opioid system. PMID- 2880877 TI - Is there a presynaptic tardive dyskinesia? PMID- 2880878 TI - Effects of small doses of bromazepam on pupillary function and on flicker perception in normal subjects. PMID- 2880879 TI - Comparison of met-enkephalin-, dynorphin A-, and neurotensin-immunoreactive neurons in the cat and rat spinal cords: I. Lumbar cord. AB - This study compared the distribution of methionine enkephalin-, dynorphin A 1-8-, and neurotensin-immunoreactive (IR) perikarya in laminae I and IV-VII of selected segments of lumbar spinal cord of cat(L5) and rat(4). Immunoreactive neurons for each peptide were found throughout the dorsal horn and dorsal lamina VII but were quantified only within laminae I and IV-VII. In lamina I, both large (greater than 20 micron) and small (less than 20 micron) IR neurons were identified. Large IR neurons for each peptide in both species resembled Waldeyer neurons studied by Golgi stain and were outnumbered by small IR neurons. Comparison among the laminae of the distribution of met-enkephalin IR neurons showed a similar pattern in the two species with the majority of IR neurons (greater than 65%) in laminae V and VI. Differences in laminar distribution occurred between species for the other peptides. Dynorphin IR neurons were greatest in number in lamina V in rat but greatest in number in laminae I and V in cat. Neurotensin IR neurons occurred predominantly in cat lamina I but were nearly equal in density in rat laminae I and VI. The topographic distribution of each peptide in laminae V and VI was similar between the two species with IR neurons occurring laterally in lamina V and more medially in lamina VI. Comparisons between species of the numbers of IR neurons/segment indicated distinct relationships for each peptide. The number of met-enkephalin IR neurons in laminae of cat L5 was generally two times greater than the number of IR neurons in the same laminae of rat L4, except in laminae I and IV, where the numbers were nearly equal. In contrast, the number of dynorphin IR neurons in cat laminae was generally one-half the number in rat, except in lamina I, where the number in cat was two times greater than rat. A high degree of variability occurred in laminar comparisons of neurotensin IR neurons. Neurotensin IR neurons in lamina I of cat outnumbered those of rat 2:1, but in laminae IV-VII, the ratio of cat to rat IR neurons varied from 1:1 to 1:20. The met-enkephalin, dynorphin, and neurotensin IR neurons quantified in this study may be interneurons or may serve as projection neurons to brainstem and/or thalamic nuclei. The observed differences in distribution may be relevant to differences in spinal cord physiology in the two species. PMID- 2880880 TI - Distribution of opiate receptor subtypes and enkephalin and dynorphin immunoreactivity in the hippocampus of squirrel, guinea pig, rat, and hamster. AB - The distribution of enkephalin and dynorphin immunoreactivity in the hippocampus of four rodent species (gray squirrel, guinea pig, rat, and hamster) is compared with the pattern of opiate receptor subtypes (mu, delta, and kappa). The distribution of opioid peptides is fairly consistent in the anterior hippocampus of these four species. Intense immunoreactivity for dynorphin and enkephalin is found in the hilus of the dentate gyrus and in the mossy fiber system. Occasional immunoreactive processes are seen in the dentate molecular layer and scattered throughout the CA1 and CA3 fields. In the rat and hamster, an additional plexus of enkephalinergic fibers straddles both sides of the hippocampal fissure. Cells immunoreactive for both opioid peptides are located in and just superficial to the dentate granule cell layer. Opiate receptors are variably distributed in these rodent species. In the squirrel, guinea pig, and hamster, mu and kappa binding is dense in the stratum lucidum of CA3 and the molecular layer of the dentate gyrus. In the rat, dense mu and kappa binding is localized within and adjacent to the pyramidal and granule cell layers. Delta receptor patterns show additional species differences. In the rat, the delta distribution is similar to the mu and kappa patterns. In the other species, the delta binding pattern is generally the inverse of the mu/kappa pattern: most areas of the hippocampus are enriched in delta sites, whereas the stratum lucidum and the pyramidal cell layer are receptor-sparse. Thus, the stratum lucidum--site of dense terminations of mossy fibers containing opioid peptides--is characterized by selectively sparse delta receptors in four species and by selectively dense kappa receptors in three species. The three receptor subtypes, taken either individually or together and compared to the peptides, are more variably and more widely distributed throughout the hippocampus and fail to show a correspondence with opioid-peptide containing terminals. The mismatches suggest that receptor locations and densities are organized without relation to the sites of relevant transmitter release. PMID- 2880881 TI - Area postrema of the goldfish, Carassius auratus: ultrastructure, fiber connections, and immunocytochemistry. AB - The area postrema in goldfish is a dorsal midline structure in the caudal medulla spanning the level of the obex. As in other vertebrates, the sinus capillaries of the area postrema in goldfish are fenestrated. In goldfish, however, the area postrema is organized in a unique laminar fashion; from superficial to deep: meninx, vasculature, palisade layer, cell body layer, and ventral neuropil layer. Virtually all of the neurons of the area postrema exhibit tyrosine hydroxylase like immunoreactivity. Each immunoreactive neuron is essentially bipolar, with a short apical dendrite extending dorsally to reach the external basal lamina of the capillaries and a basal dendrite reaching into the subjacent layer of neuropil. The apical dendrites have no synaptic specializations and probably function as interoceptors detecting blood-borne chemicals that leak out of the fenestrated capillaries. The basal dendrites receive synaptic input both within the neuropil of the area postrema and in the commissural nucleus of Cajal into which they extend. Primary afferent fibers of the subdiaphragmatic branches of the vagus nerve terminate within the area postrema and commissural nucleus. Thus the neurons of the area postrema may serve not only as direct chemoreceptive interoceptors but may also receive input from other visceral afferent systems. PMID- 2880882 TI - [Standardization and reproducibility of gas chromatographic research on the cellular fatty acids of microorganisms]. PMID- 2880883 TI - Problematic gagging: principles of treatment. AB - The causes of problematic gagging are discussed and a behavioral method for its treatment is recommended. Four case studies illustrating the application of this approach are presented. PMID- 2880885 TI - Effect of terfenadine on methacholine-induced bronchoconstriction in asthma. AB - The dose-response effect of nonsedating H1 histamine-receptor antagonist, terfenadine, administered orally in single doses, was studied on methacholine induced bronchoconstriction in nine patients with extrinsic bronchial asthma in a double-blind, placebo-controlled, crossover trial. The doses of terfenadine used were 60 mg, 120 mg, and 180 mg, producing small but significant bronchodilator effect with all three doses at 2 hours. This response was still present at 4 hours. However, the provocative dose causing a 20% fall in FEV1 for methacholine was unaffected by all three doses of terfenadine. The bronchodilator response induced by antihistamines, including terfenadine, suggests an increased resting tone mediated by the constant presence of free histamine in the vicinity of H1 receptors in the airways and that methacholine acts directly on the airway muscarinic receptors and is not involved in local histamine release. PMID- 2880884 TI - Chronic renal and neurohumoral effects of the calcium entry blocker nisoldipine in patients with congestive heart failure. AB - Nisoldipine, a calcium entry blocker, was given to 10 patients with congestive heart failure. During a 2 month follow-up period, 7 of the 10 patients were readmitted with pulmonary edema; daily furosemide doses were increased (128 +/- 87 to 192 +/- 135 mg/day, p less than 0.01), and plasma creatinine increased (1.5 +/- 0.5 to 1.8 +/- 0.6 mg/dl, p less than 0.05) (all values mean +/- SD). Despite this unfavorable clinical course, nisoldipine caused some beneficial chronic (1 month) hemodynamic effects. It decreased systemic vascular resistance (from 1,781 +/- 229 to 1,306 +/- 345 dynes X s X cm-5, p less than 0.01), decreased mean arterial pressure (from 88 +/- 0 to 74 +/- 4 mm Hg, p less than 0.001) and increased stroke volume index (from 27 +/- 6 to 33 +/- 9 ml/min per m2, p less than 0.02). Heart rate, pulmonary capillary wedge pressure and stroke work index did not change. However, nisoldipine's chronic renal and neurohumoral effects were not as favorable. These were assessed during a 5 hour water load (15 ml/kg body weight of 5% dextrose in water) and compared with the effects of a water load before therapy. Nisoldipine did not change creatinine clearance or sodium excretion, but decreased water excretion (from 58 +/- 35 to 46 +/- 40% of water load in 5 hours). Over this 5 hour study, mean plasma vasopressin was also higher with nisoldipine (1.9 +/- 2.3 versus 2.7 +/- 3.2 pg/ml, p less than 0.05), but mean plasma aldosterone was lower (67 +/- 31 to 47 +/- 27 mg/dl, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2880886 TI - Natural food constituents and food additives: the pharmacologic connection. PMID- 2880887 TI - Neuroleptics and the elderly. PMID- 2880889 TI - [Cerebrovascular complications in obstetrics and beta mimetic drugs]. AB - The authors report a new case of a cerebro-vascular accident following the stopping of an infusion of a beta-mimetic drug to inhibit uterine contractions. The clinical symptomatology and the spontaneous recovery (over more than 6 months) makes it correct to call this pathological condition "an acute cerebral vascular disorder of a benign nature". It is not known how the cerebral vessels were affected by the beta-mimetic drugs. PMID- 2880888 TI - Direct evidence that pancuronium and gallamine enhance the release of norepinephrine from the atrial sympathetic nerve by inhibiting prejunctional muscarinic receptors. AB - The effect of different non-depolarizing muscle relaxants (gallamine, pancuronium, vecuronium, D-tubocurarine) on [3H]norepinephrine release in response to electrical stimulation was studied in isolated guinea-pig atrium. High pressure liquid chromatography combined with electrochemical and radiochemical detection revealed that the released radioactivity was mainly in the form of [3H]norepinephrine release. Oxotremorine, a pure muscarinic agonist, reduced the release of tritium. Gallamine and pancuronium, like atropine, prevented the inhibitory effect of oxotremorine. D-Tubocurarine and vecuronium had no such effect. These findings indicate that gallamine and pancuronium exert a presynaptic antimuscarinic, atropine-like effect, by inhibiting muscarinic receptors located on the axon terminals of sympathetic neurons thereby enhancing norepinephrine release. It is suggested that this phenomenon might play some role in tachycardia observed during surgical anaesthesia when gallamine or pancuronium have been administered. PMID- 2880891 TI - Labeling of structural elements at the ventral plasma membrane of fibroblasts with the immunogold technique. AB - We investigated the organization of two structural elements (microfilaments and clathrin coated structures) at the ventral plasma membrane in fibroblasts. The methods employed included exposure of the inner face of the ventral plasma membrane by lysis-squirting, labeling the exposed structures with specific antibodies conjugated with colloidal gold, and platinum-carbon replica techniques. The results demonstrate that this regimen combines good ultrastructural preservation with unambiguous identification of structural elements associated with the plasma membrane. This method is therefore reliable and can be generally used to explore in detail the ultrastructural organization of the plasma membrane. PMID- 2880890 TI - Enzymatic histochemistry of mouse kidney in plastic. AB - Two-micrometer sections of methacrylate-embedded kidney were used to investigate the enzymatic activities of mouse kidney where the proximal tubule and Bowman's capsule from the same corpuscle were viewed in the same section. Alkaline phosphatase, acid phosphatase, 5'-nucleotidase, gamma-glutamyl transpeptidase, N acetyl-beta-glucosaminidase, leucine aminopeptidase, alpha-naphthyl butyrate esterase, and adenosine triphosphatase activities were observed in the proximal tubule, but only 5'-nucleotidase, alpha-naphthyl butyrate esterase, and alkaline phosphatase were observed in the squamous portion of the parietal epithelium of Bowman's capsule. The use of methacrylate-embedded tissue allowed more precise localization of enzymatic activity than is possible with most frozen sections. This may provide interesting applications not only for characterization of kidney diseases but also for characterization of other normal and abnormal tissues. PMID- 2880892 TI - The public health function: responsibility for control of infection in hospitals. PMID- 2880893 TI - Hospital epidemiology of Pseudomonas aeruginosa from patients with cystic fibrosis. AB - Pseudomonas aeruginosa colonizes the respiratory tract of most older patients with cystic fibrosis. The means by which these bacteria are acquired and the risk for patient-to-patient spread among subjects with cystic fibrosis are poorly understood. We studied the spread of Ps. aeruginosa within a hospital environment. Pseudomonas was rarely recovered from the inanimate environment surrounding patients with cystic fibrosis or from hand or rectal cultures of patients who were colonized in the oropharynx. There was transient cross colonization with Ps. aeruginosa between patients with cystic fibrosis sharing a hospital room in three of seven pairs studied. In all cases the "new" isolate was recoverable only once and was not found during a 2-year follow-up. Three of four sibling pairs with cystic fibrosis shared the same Ps. aeruginosa serotype(s). The risk of sustained cross-colonization by Ps. aeruginosa between patients with cystic fibrosis appears to be minimal, except under conditions of prolonged close contact. PMID- 2880894 TI - A surface test for virucidal activity of disinfectants: preliminary study with herpes virus. AB - A test was developed to assess the surface activity of disinfectants against dried viral preparations. In this preliminary study a variety of disinfectants was tested against herpes virus. The results showed that 2% alkaline glutaraldehyde and 70% ethanol or isopropanol were effective in 1 min. Hypochlorite solutions (2500 ppm av. Cl2) were effective in 5 min, but povidone iodine (10%) was slower in action and a clear soluble phenol showed uncertain activity at 5 and 10 min. High concentrations of alcohols (above 95%), two quaternary ammonium compounds and 0.5% aqueous chlorhexidine showed little activity in 10 min. PMID- 2880896 TI - Acute hepatitis B following gynaecological surgery. PMID- 2880895 TI - The effect of handcream on the antibacterial activity of chlorhexidine gluconate. AB - A series of handwashing experiments compared the residual effect on Escherichia coli of non-medicated soap, chlorhexidine detergent followed by an anionic handcream, chlorhexidine detergent followed by a non-ionic handcream and chlorhexidine detergent alone. Handcreams containing an anionic emulsifying agent reduced the antibacterial effect of chlorhexidine. PMID- 2880897 TI - A study of the prevalence of markers of hepatitis B infection in hospital staff. AB - Five hundred and sixty-one members of the nursing, dental and junior medical staff of a teaching hospital were tested for serological evidence of hepatitis B infection using the markers HBsAg, anti-HBs and anti-HBc. Overall marker prevalence rates, indicating both current and past infections, were: dental staff 1.1%; nursing staff 3.2%; junior medical staff 6.0%. These results reflect relative risk of occupational exposure. PMID- 2880898 TI - Group JK coryneform bacteria. PMID- 2880899 TI - The risk of infection with hepatitis B virus in relation to length of hospital employment. AB - A sero-epidemiological study was carried out on a representative sample of employees of the Hospital Clinico 'San Cecilio' in an attempt to quantify the influence of the time spent working in the hospital on the risk of becoming infected by hepatitis B virus. The results show that the rate of infection by HBV is directly proportional to the length of employment in the hospital, with a probability of infection between 0.6% and 1.4% for each working year. PMID- 2880900 TI - Resistant coagulase-negative staphylococci in hospital patients. AB - Patients admitted to a district general hospital for general surgery were examined on admission and at weekly intervals for carriage of Staphylococcus aureus and coagulase-negative staphylococci (CNS) in the anterior nares. Thirty two of 100 patients were colonized with CNS resistant to three or more antibiotics on admission to hospital. Two weeks later, 16 of 22 patients who remained in hospital carried resistant CNS; in 11 of these 16 patients the resistant strain was selected or acquired while the patient was in hospital. PMID- 2880901 TI - An outbreak of Campylobacter jejuni infection in a neonatal intensive care unit. AB - During a period of 2 weeks Campylobacter jejuni infection was diagnosed in seven infants in a neonatal intensive care unit. An identical serotype of Camp. jejuni was found in five of the cases. Investigations suggested that a common source of infection or infection acquired from mothers during delivery were unlikely. The dates of onset and the common serotype indicate that the outbreak may have been caused by person-to-person spread. PMID- 2880902 TI - The international spread of methicillin-resistant Staphylococcus aureus. AB - A genetic analysis of representative methicillin-resistant Staphylococcus aureus (MRSA) being isolated in London and Dublin hospitals has demonstrated that the epidemic strains from two London hospitals are different from the Dublin strains, but indistinguishable from the epidemic strains of eastern Australia. The possibility that some strains of MRSA are more likely than others to spread within hospitals is discussed. PMID- 2880903 TI - Does instillation of chlorhexidine into the bladder of catheterized geriatric patients help reduce bacteriuria? AB - A randomized prospective trial compared the effect on the bacterial flora of the urine of the instillation of chlorhexidine or of normal saline into the bladder of two groups of elderly patients with indwelling urinary catheters. There was no reduction in urinary bacterial count in either group of patients. PMID- 2880904 TI - An outbreak of rotavirus infection in a geriatric hospital. AB - We describe an outbreak of rotavirus infection in a geriatric hospital. The outbreak lasted for 6 weeks, and affected 14 patients of 68 at risk. Diarrhoea was the main symptom, lasting only 1 day in most patients. Rising or high rotavirus antibody titres were demonstrated in six patients. Of 96 staff only one member was infected. PMID- 2880905 TI - Diagnostic amniocentesis and bacteraemia. AB - Thirty antenatal patients with intact membranes were studied to determine the incidence of bacteraemia induced by transabdominal amniocentesis. No bacteraemias were detected following the procedure. Antibiotic prophylaxis is probably not warranted for immunocompetent hospitalized patients undergoing amniocentesis. PMID- 2880906 TI - Hot air electric hand driers compared with paper towels for potential spread of airborne bacteria. AB - Hot air hand driers are increasingly used in both public areas and hospitals, but there is little literature on their bacteriology. Four units were examined by comparing the bacterial aerosols released from hands during use by sets of twelve subjects with those released by paper towels. Tests on two units also included hand imprints on agar plates for detection of residual bacteria. No significant difference between aerosols liberated by towels and driers were observed for two units, while the other two generated significantly fewer aerosols than towels. Impression plates revealed similar numbers of bacteria on the hands after drying by either method. Hot air hand driers appear safe from a bacteriological viewpoint. PMID- 2880907 TI - The primordial MRSA? PMID- 2880908 TI - Guidelines for the control of epidemic methicillin-resistant Staphylococcus aureus. PMID- 2880909 TI - Sterility of incontinence pads and sheets. PMID- 2880910 TI - Possible transmission of methicillin-resistant Staphylococcus aureus by expressed human breast milk. PMID- 2880911 TI - Mechanism of action of a new prostaglandin antihypertensive, viprostol [CL 115 347; (dl)-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2 methyl ester]: (II). Effects on the adrenergic nervous system. AB - Viprostol [(dl)-15-deoxy-16-hydroxy-16(alpha/beta)-vinyl-prostaglandin E2 methyl ester; CL 115 347] is a new orally and transdermally active antihypertensive agent that exerts its major antihypertensive action by vasodilation. The present studies were conducted to examine its effects on the adrenergic nervous system. In cats, viprostol did not inhibit renal sympathetic nerve discharge (RSND) monitored at the postganglionic region, indicating that nerve transmission or conduction was not blocked at the ganglion or the pre- or postganglionic fibres. In cat nictitating membrane preparations in situ, viprostol partially blocked the membrane contractile response to exogenous epinephrine and norepinephrine, as well as to electrical stimulation of pre- and postganglionic fibres. In spontaneously hypertensive rats (SHR), viprostol partially blocked the vasopressor response of exogenous norepinephrine and epinephrine specifically without influencing that of angiotensin II. All these suggest that viprostol produced weak alpha-adrenoceptor blockade. Viprostol did not antagonize the tachycardia induced by stimulation of the discrete segments at C7-T1 (cardio accelerator) of the spinal cord in pithed SHR, suggesting that viprostol did not activate the presynaptic alpha-adrenoceptors. Viprostol significantly inhibited the increase in blood pressure induced by electrical stimulation of the spinal cord at T7-T9 in pithed SHR, probably due to postsynaptic alpha-adrenoceptor blockade. In conclusion, viprostol produced weak, but statistically significant alpha-adrenoceptor blockade which may contribute partially to its antihypertensive action. PMID- 2880912 TI - HLA-DP and HLA-DO genes in presumptive HLA-identical siblings: structural and functional identification of allelic variation. AB - We analyzed HLA class II genomic polymorphisms in three families in which bone marrow transplantation was performed between individuals presumed to be HLA identical, but in which unexplained mixed lymphocyte culture reactivity was observed. These families were characterized by classical HLA serology, MLC, and DP typing. In each family, a pair of "HLA-identical" siblings demonstrated a small proliferative response in bidirectional MLC. Southern blotting analysis performed with cDNA probes for DQ alpha, DP alpha, and DP beta identified DP genomic differences in each case. Hybridization of Bgl II-digested genomic DNA with a DP alpha cDNA probe revealed three prominent polymorphic fragments (7.7, 5.8, and 3.7 kb), which discriminated between presumptive identical siblings and indicated crossover events within HLA. Similarly, hybridization of SstI-digested genomic DNA with a DP beta cDNA probe, although resulting in a more complex pattern, identified DP genomic disparity between the presumed HLA identical siblings. Hybridization of SstI-digested DNA from two families with evidence of DP recombination was performed by using an oligonucleotide probe specific for the newly described HLA class II gene DO beta. Two major polymorphic fragments, at 6.2 and 3.3 kb, segregated in these families and localized the crossovers flanking the DO beta gene between the DQ and DP loci. The contribution of the antigenic differences marked by these HLA DP and DO DNA polymorphisms to allorecognition in MLR and in graft-vs-host disease are discussed. PMID- 2880913 TI - Immunoaffinity chromatography utilizing monoclonal antibodies. Factors which influence antigen-binding capacity. AB - Differences in antigen-binding capacity of a monoclonal antibody coupled to Sepharose under varying conditions were explored. The extent of cyanogen bromide activation, and the pH of the coupling reaction had a profound effect upon the rate of antibody coupling, but only small differences in antigen-binding capacity were observed if the antibody coupling reaction was terminated when 80-90% of the antibody was covalently coupled to Sepharose. However, if antibody was incubated with activated resin until 100% coupling was attained, the antigen-binding capacity of the resulting immunoadsorbent decreased significantly. Monoclonal antibody coupled to Sepharose via an N-hydroxysuccinimide ester linkage and approximately half the antigen-binding capacity of antibody coupled by CNBr activation. Concentrations of monoclonal antibodies as high as 13 mg/ml of packed resin could be used without noticeable steric hindrance. PMID- 2880914 TI - Isolation of the MHC genes encoding the tumour-specific class I antigens expressed on a murine fibrosarcoma. AB - The C3H UV-induced fibrosarcoma, 1591, is highly immunogenic and, therefore, is readily rejected when transplanted into immunocompetent syngeneic recipients. Previous analysis of 1591 with tumour-specific or H-2-reactive monoclonal antibodies revealed that this antigenicity might be due to the expression of two novel class I major histocompatibility complex (MHC) antigens. In this report we describe the molecular cloning and initial characterization of three genes which account for all of the unique serological class I reactivities observed on this tumour. These include two distinct, but highly conserved, H-2L-like genes, and a third gene the product of which bears determinants which are characteristic of both the tumour and of class I products of the H-2k haplotype. Moreover, each of these genes contains a polymorphic restriction enzyme fragment which is detected in the class I sequences of 1591 relative to normal C3H tissue. Since the expression of these polymorphic class I sequences is relevant to the immunogenicity of 1591, the mutational events by which these genes were generated may be significant to the immunobiology of this tumour. PMID- 2880915 TI - Loss of polymorphic restriction fragments of class I and class II MHC genes in a malignant melanoma. AB - DNAs from human malignant melanoma cells and autologous peripheral blood lymphocytes were evaluated by Southern blot analysis with probes for class I and II HLA genes. DNA of melanoma cells digested with PvuII, EcoRI and BglI and hybridized with a DR beta probe showed a loss of several fragments when compared with DNA from lymphocytes. The same DNAs were not distinguishable when hybridized with a DQ beta probe. Analysis of melanoma and autologous lymphocyte DNAs from the same patient with a class I cDNA, after digestion with several endonucleases, revealed a further loss of fragments in melanoma cells. Comparison of restriction fragment patterns of melanoma and lymphocytes with those of homozygous, serologically-typed cell lines indicated that melanoma cells have lost fragments diagnostic of DR2 and A1 antigens. A densitometric analysis of signals of several oncogenes in comparison with that of DR indicated that a duplication of the remaining DR allele had occurred in melanoma cells. PMID- 2880916 TI - Cutaneous infection with Mycobacterium gordonae. AB - A case of cutaneous infection with Mycobacterium gordonae and other reports of extrapulmonary infection due to this organism are reviewed. This case confirms the pathogenic potential of M. gordonae which must now be included among the scotochromogens capable of causing cutaneous disease. Isolates of this organism should be tested against a full range of antimicrobial agents since traditional antituberculous therapy may be of limited efficacy. Pending the results of in vitro susceptibility testing, amikacin, ethambutol, rifampicin and co-trimoxazole are suggested as empirical therapy for infections caused by this organism. PMID- 2880917 TI - Simultaneous infections with human T cell leukemia virus type I and the human immunodeficiency virus. AB - Four adults form four separate households were found to have simultaneous retroviral infections with human T cell leukemia virus type I (HTLV-I) and human immunodeficiency virus (HIV). These individuals were seropositive for the HTLV-I env transmembrane protein p21E, and all had antibodies to the HTLV-I core polypeptide p24. All four patients also had antibodies to the HIV env transmembrane polypeptide p41E and to the HIV core polypeptide p24. HTLV-I was isolated from peripheral blood lymphocytes of all four individuals, and both viruses were isolated from two of them. Evidence of HIV transmission was noted in the family contacts. Eight of 10 children of these four adults were seropositive for HIV, presumably because of perinatal transmission from infected mothers. Two of five spouses of these adults were examined; these spouses had antibodies to HIV and were positive for virus. No evidence of HTLV-I transmission was noted in these families. PMID- 2880919 TI - You and malpractice stress. IV: The office staff's perspective. PMID- 2880918 TI - Secretion of somatostatin and its physiologic function. AB - Somatostatin, initially described as a growth hormone release-inhibitory peptide 14 amino acids in length, has been shown to be one of a family of related peptides. It is ubiquitous in distribution and versatile as a paracrine factor with a potentially important role in the regulation of gut, pancreatic, and nervous system function in addition to its well-recognized influence on the pituitary secretion of growth hormone and thyroid-stimulating hormone. With the development of new super agonists, it has become possible to manipulate the endocrine milieu, to modify gut, pancreatic, and pituitary function, and in the case of several diseases such as acromegaly, intractable diarrhea, and carcinoid, to make a significant advance in therapy. PMID- 2880920 TI - Effect of nutrition and immunization against somatostatin on growth and insulin like growth factors in sheep. AB - The effect of immunizing against somatostatin (SRIF), with SRIF conjugated to bovine thyroglobulin, was examined in cross-bred sheep fed either cut pasture or lucerne pellets. Plasma concentrations of GH were unaffected by SRIF immunization, but were lower in pellet-fed sheep. Plasma concentrations of insulin-like growth factor I (IGF-I) increased after immunization in sheep on both diets. Pasture-fed sheep had lower plasma concentrations of IGF-I than those on pellets. Sheep showed a small increase in growth rate in response to immunization. Immunization had no effect on carcass composition and did not affect plasma concentrations of IGF-II, free fatty acids or glucose. The results show that even though SRIF immunization increases plasma concentrations of IGF-I, it does not necessarily result in a large increase in growth rate. PMID- 2880921 TI - Somatostatin partially reverses desensitization of somatotrophs induced by growth hormone-releasing factor. AB - The effect of somatostatin on GH-releasing factor (GRF)-induced desensitization of somatotrophs was studied in vitro. Primary cultures of rat anterior pituitary cells pretreated for 4 or 18 h with GRF(1-40) (100 nmol/l) showed a 50% or greater reduction in maximal GH release when rechallenged with 10 nmol GRF/l. Rechallenge GRF dose-response curves were either very flat, making accurate measurement of the dose giving 50% maximum stimulation (ED50) impossible, or the ED50 concentration was increased from 0.3 nmol/l (untreated) to 2 nmol/l (GRF pretreated). Although GRF pretreatment reduced cellular GH content by 40-50%, correction for this did not restore GRF responsiveness measured in terms of maximal GRF-stimulated/unstimulated GH release (maximal/basal ratio), or the GRF ED50 concentration. Maximal/basal GH release per 4 h from GRF-pretreated cells was reduced when cells were rechallenged with forskolin (5 mumol/l) or calcium ionophore (A23187; 10 mumol/l), to the same extent as when rechallenged with 10 nmol GRF/l. Although this might be explained by a reduction in the pool of releasable GH, an alternative explanation is that pretreatment with GRF d disrupts the GH release mechanism(s) at a common step(s) beyond cyclic AMP generation and Ca2+ influx. Co-incubation of cells with somatostatin and GRF (100 nmol/l) partially reversed the desensitizing action of GRF during both 4- and 18 h pretreatments in a dose-dependent manner, with 1 mumol somatostatin/l being most effective. Maximal GRF (100 nmol/1-stimulated/basal GH release was 4.4 +/- 1.0 (mean +/- S.E.M., n = four experiments), 1.55 +/- 0.09 and 2.43 +/- 0.1 for control, GRF-pretreated (4 h) and GRF plus somatostatin-pretreated cells respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2880922 TI - Influence of the cryptorchid testis on the regeneration of rat Leydig cells after administration of ethane dimethane sulphonate. AB - Leydig cells were selectively eliminated from the testis by treatment with the cytotoxin, ethane dimethane sulphonate. Rats were then made unilaterally cryptorchid and the morphological and functional response of the interstitial tissue in abdominal compared with scrotal testes was examined for up to 8 weeks. Regeneration of new Leydig cells occurred more rapidly in the interstitial tissue of abdominally cryptorchid testes compared with the interstitial tissue of contralateral scrotal testes. More rapid recovery of Leydig cells was coincident with significant increases in the bioactivity of a local factor(s), collected from interstitial fluid of cryptorchid testes, which stimulated testosterone production by isolated Leydig cells in vitro. These results support the theory that the production of a local factor(s) plays a role in the regeneration of Leydig cells and is affected by damage to the seminiferous epithelium. PMID- 2880923 TI - Induction of cystine transport activity in mouse peritoneal macrophages. AB - Uptake of cystine was investigated in mouse peritoneal macrophages. The rates of the uptake of cystine in resident macrophages or macrophages elicited by some irritants were very low, but a drastic increase was observed when the cells were cultured in vitro. This increase was time-dependent and required protein synthesis. In macrophages elicited by thioglycollate broth, the rate of the uptake of cystine increased by about 40-fold after 16 h in culture. Contrary to the uptake of cystine, the rates of uptake of some neutral amino acids did not change markedly during culture. We characterized the induced activity of the cystine uptake in macrophages elicited by thioglycollate broth. Cystine was taken up in an Na+-independent and pH-sensitive manner, and the uptake was potently inhibited by extracellular glutamate and the analogous anionic amino acids, but not by aspartate. The activity of the glutamate uptake was also induced during the culture in a way similar to that of cystine uptake, and the uptake of glutamate was potently inhibited by cystine. From these results we concluded that the uptake of cystine and glutamate in macrophages was mostly mediated by a single transport system similar to the ones previously reported in human fibroblasts and some other cells. As a consequence of the induction of the activity of the cystine uptake, glutathione levels in macrophages doubled during culture, and a thiol compound, presumably cysteine, was released into the culture medium and accumulated there. When the macrophages were cultured hypoxically, the induction of the cystine uptake activity was markedly depressed, suggesting an involvement of oxygen in the induction. PMID- 2880924 TI - [Determination of enzyme activities in urine of patients with calcium oxalate calculi]. AB - The catalytic activity of lactate dehydrogenase, gamma-glutamyltransferase, alkaline phosphatase, alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase has been measured in 24 h urines of patients with a calcium oxalate calculus (9 men, 11 women) and has been compared with those of a reference collective (11 men, 10 women). The diagnostic sensitivity and the diagnostic specificity have been calculated according to four different discrimination methods in which the diagnostic sensitivity lies between 65% and 100%, the diagnostic specificity between 72% and 100%. Within the reference group there was a correlation between the excretion of the three brush-border enzymes, whereas within the group of patients only a correlation between gamma-glutamyltransferase and N-acetyl-beta-D glucosaminidase was observed. From this pathophysiological conclusions can be drawn. PMID- 2880925 TI - Antihistamine-decongestants and acute otitis media. PMID- 2880926 TI - Long-term effect of radioiodine therapy on the thyroid antibodies in the patients of Graves' disease with postirradiation hypothyroidism. PMID- 2880927 TI - Violent behavior in schizophrenic inpatients. AB - We undertook a retrospective survey of assaultive behavior in 140 psychiatric inpatient research volunteers who had not previously responded well to neuroleptic treatment. Forty-one of 97 patients with schizophrenia became assaultive during their hospitalization, whereas only four of 43 patients with other diagnoses became assaultive (p less than .0001). Most assaults were not a significant threat to the attacked person, but a small number were highly dangerous. Assaultive patients were significantly younger, and a greater proportion had a previous history of violence, compared with nonassaultive patients. A previous history of violent behavior was linked to more previous hospitalizations, indicating that such behavior might be associated with a poor prognosis. PMID- 2880928 TI - Efflux of putative transmitters from superfused rat brain slices induced by low chloride ion concentrations. AB - Slices of rat cerebral cortex, preloaded with [14C]gamma-aminobutyric acid (GABA) and either [3H]5-hydroxytryptamine (5-HT) or [3H]noradrenaline, were superfused with media in which varying concentrations of Cl- had been replaced with other monovalent anions. Rapid reduction of [Cl-], by superfusion with media containing instead the impermeant anions propionate, isethionate, gluconate, or methyl sulphate, caused increases in the efflux of tritiated biogenic amines, but the increase in that of [14C]-GABA was not significant. The increased efflux of [3H]5 HT evoked by superfusion with low Cl- levels when propionate was the replacement anion, was transient and was linearly related to the log[Cl-]-1. It was not affected by removal of Ca2+ or by addition of 10 mM Mg2+ and was delayed but not abolished by tetrodotoxin. The low Cl(-)-evoked efflux of [3H]5-HT was not affected by pretreatment with neuronal reuptake blockers but was inhibited by picrotoxin, strychnine, and 4-acetamido-4-isothiocyanostilbene-2,2-disulphonic acid and was enhanced by glycine. Muscimol and GABA were without effect. These observations are taken to indicate that the efflux of biogenic amines is brought about by terminal depolarisation due to outward movement of Cl- in low chloride containing media. They are of relevance to other physiological and pharmacological studies in which anion concentrations are manipulated and suggest that the anion-evoked release phenomenon may provide a model for the analysis of Cl(-)-dependent mechanisms in nerve terminals. PMID- 2880929 TI - Selective inhibition of synaptosomal gamma-aminobutyric acid uptake by triethyllead: role of energy transduction and chloride ion. AB - Triethyllead (TEL) is a CNS neurotoxin producing bizarre neurobehavioral changes. The principal objective of this study was to determine if TEL-induced defects in energy metabolism were responsible for the inhibition of synaptosomal Na+ dependent high-affinity uptake of gamma-aminobutyric acid (GABA). A dose dependent inhibition of GABA uptake (ID50 = 10 microM TEL) was found during 30-s incubations. Uptake of glutamate was more resistant to the inhibitory effects of TEL. A TEL-induced Cl(-)-dependent synaptosomal deficit of ATP was observed. Such deficit in high-energy phosphate was time-dependent and did not occur in the absence of Cl- or as early as 30 s. Inhibition of GABA uptake, on the other hand, was a Cl(-)-independent phenomenon and was observed at as early as 30 s. TEL was not competitive with Na+ or GABA itself, as the effects of TEL were not overcome with high [Na+] or [GABA]. These results indicate that the locus of TEL inhibition of GABA uptake is not a Cl(-)-dependent event and does not involve a perturbed transmembrane electrochemical gradient, due to either an observed mitochondrial defect or an inhibition of Na+, K+-ATPase directly. PMID- 2880931 TI - Brain endo-oligopeptidase A, a putative enkephalin converting enzyme. AB - Endo-oligopeptidase A, highly purified from the cytosol fraction of bovine brain by immunoaffinity chromatography, has been characterized as a thiol endopeptidase. This enzyme, known to hydrolyze the Phe5-Ser6 bond of bradykinin and the Arg8-Arg9 bond of neurotensin, has been shown to produce, by a single cleavage, Leu5-enkephalin or Met5-enkephalin from small enkephalin-containing peptides. Enkephalin formation could be inhibited in a concentration-dependent manner by the alternative substrate bradykinin. The optimal substrate size was found to be eight to 13 amino acids, with enkephalin the only product released from precursors in which this sequence is immediately followed by a pair of basic residues. However, the specificity constants (kcat/Km) obtained for endo oligopeptidase A hydrolysis of bradykinin, neurotensin, and dynorphin B are of the same order, a result indicating that the substrate amino acid sequence is not the only factor determining the cleavage site of this enzyme. PMID- 2880930 TI - L-phenylalanyl-L-glutamate-stimulated, chloride-dependent glutamate binding represents glutamate sequestration mediated by an exchange system. AB - Stimulation of glutamate binding by the dipeptide L-phenylalanyl-L-glutamate (Phe Glu) was inhibited by the peptidase inhibitor bestatin, suggesting that the stimulation was caused by glutamate liberated from the dipeptide and not by the dipeptide itself. It further suggests that this form of glutamate binding should be reinterpreted as glutamate sequestration and that stimulation of binding both by dipeptides and after preincubation with high concentrations of glutamate is likely to be due to counterflow accumulation. Several other criteria indicate that most of glutamate binding stimulated by chloride represents glutamate sequestration: Binding is reduced when the osmolarity of the incubation medium is increased, when membranes incubated with [3H]glutamate are lysed before filtration, and when membranes are made permeable by transient exposure to saponin. Moreover, dissociation of bound glutamate after a 100-fold dilution of the incubation medium is accelerated about 50 times by the addition of glutamate to the dilution medium. This result would be anomalous if glutamate were bound to a receptor site; it suggests instead that glutamate is transported in and out of membrane vesicles by a transport system that preferentially mediates exchange between internal and external glutamate. Glutamate binding contains a component of glutamate sequestration even when measured in the absence of chloride. Sequestration is adequately abolished only after treating membranes with detergents; even extensive lysis, sonication, and freezing/thawing may be insufficient. PMID- 2880932 TI - Modulatory effect of dopamine on high-affinity glutamate uptake in the rat striatum. AB - In vivo electrical stimulation of the frontal cortical areas was found to enhance sodium-dependent high-affinity glutamate uptake (HAGU) measured in rat striatal homogenates. This activating effect was counteracted by in vivo administration of apomorphine and by in vitro addition of dopamine (DA; 10(-8) M) in the incubation medium, and potentiated by in vivo haloperidol administration. At the doses used, the dopaminergic compounds had no effect on basal HAGU. alpha-Methylparatyrosine pretreatment was found to enhance slightly basal HAGU as well as the activating effects of cortical stimulation. Interestingly enough, lesion of dopaminergic neurons by substantia nigra injection of 6-hydroxydopamine (6-OHDA) did not cause any significant change either in basal HAGU or in the effect of cortical stimulation. Measurement of DA effects in vitro in experiments combined with in vivo manipulations of the dopaminergic nigrostriatal and corticostriatal systems showed that the capacity of DA to inhibit striatal HAGU depends directly on the level of the uptake activation reached over basal value. These results suggest that under physiological conditions, the dopaminergic nigrostriatal pathway exerts a modulatory presynaptic action on corticostriatal glutamatergic transmission, counteracting increasing glutamatergic activity. In the case of chronic DA depletion induced by 6-OHDA, striatal adaptations may occur modifying the mechanisms acting at corticostriatal nerve terminal level. PMID- 2880933 TI - Somatostatin neurons in the small intestine of the guinea pig: a light and electron microscopic immunocytochemical study combined with nerve lesion experiments by laser irradiation. AB - Somatostatin-like immunoreactive neurons are present in both the myenteric and the submucous plexuses of the small intestine of the guinea pig. Dense varicosities of immunopositive nerve fibres surround the ganglionic cells, some of which also display somatostatin-like immunoreactivity. Immunoelectron microscopy demonstrated axo-somatic synapse formation between the somatostatin immunoreactive neuronal elements. Nerve lesion experiments using argon laser irradiation showed that most of the somatostatin-like immunoreactive fibres of the myenteric plexus were directed anally, whereas those of the submucous plexus had no directional polarity. PMID- 2880934 TI - The behaviour of OKT3-, OKT4- and OKT8-positive cells during phases of elevated spontaneous chemiluminescence activity (CL-A) in multiple sclerosis patients. A serial study. AB - The chemiluminescence activity (CL-A; synonym = burst activity, BA) and the percentage of OKT3-, OKT4- and OKT8-positive peripheral blood cells were serially examined in four control persons and in eight patients with multiple sclerosis. When the OKT values obtained in phases of increased CL-A (clinical remission) were compared with those of the control group, the percentage of OKT3-positive cells was reduced (P = 0.014), and that of OKT4-positive cells increased (P = 0.014); there were no significant changes in the percentage of OKT8-positive cells (P = 0.171). After the CL-A had returned to normal values, the OKT4 positive cells remained elevated (P = 0.029), whereas the OKT3- (P = 0.342) and OKT8-positive cells (P = 0.443) showed no significant changes. When in the same patients, phases of increased CL-A were compared with phases in which values were not elevated, a reduced percentage of OKT3-positive cells was found in phases with increased CL-A (P = 0.031); however, the OKT4-positive and OKT8-positive cells did not differ significantly (P = 0.156 and 0.281). PMID- 2880935 TI - Stimulation of adenylate cyclase in relation to dopamine-induced long-term enhancement (LTE) of muscarinic depolarization in the rabbit superior cervical ganglion. AB - Dopamine (DA) induction of the long-term enhancement (LTE) of the slow muscarinic depolarizing response to methacholine (MCh), equivalent to the slow EPSP (S EPSP), was previously found to be mimicked by exogenous cyclic AMP (cAMP) in the rabbit superior cervical ganglion (SCG). DA-induced LTE of the S-EPSP was shown to be depressed by some DA antagonists. We now show that DA (15 microM), its analog, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN), and a D2 receptor antagonist, metoclopramide, each can induce both LTE of MCh depolarization and an increase in ganglionic cAMP. Conversely, antagonists of DA induced LTE also depress DA-induced rises in cAMP; these antagonists include haloperidol (1 microM), both (+) and (-) enantiomers of butaclamol (0.7-7 microM), flupenthixol (1 microM), and (+)-R-8-chloro-2,3,4,5-tetrahydro-3-methyl 5-phenyl-1H-3-benzazepine-7-o l (SCH-23390) (7 microM). The selective D2 antagonists sulpiride (10 microM) and domperidone (10 microM) affect neither DA action. Alpha-2 adrenergic agonists (alpha-methyl-norepinephrine and clonidine) produce no LTE; alpha-antagonist dihydroergotamine (35 microM) does not affect either DA action, although it can completely block the hyperpolarizing response to DA or other catecholamines. Beta-antagonist propranolol (5 microM) partially depresses DA-induced rises in cAMP but has no effect on the DA-induced LTE. (Butaclamol and propranolol in combination can completely block the cAMP rise induced by DA.) Beta-agonist isoproterenol can induce appreciable LTE of MCh depolarization, but this LTE is not depressed by propranolol (10 microM). Isoproterenol can elicit a substantial rise in cAMP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2880936 TI - The toxic effects of ethylcholine mustard aziridinium ion on cholinergic cells in the chicken retina. AB - The chicken retina has been used to examine the toxicity of a highly reactive chemical analog of choline, ethylcholine mustard aziridinium ion (ECMA). Following a single intravitreal injection, retinas were analyzed biochemically for CAT and AChE activities, and GABA, glycine, and dopamine levels. Retinas were also examined using histofluorescence for dopamine histochemistry, for AChE, and immunohistochemistry with antibodies to CAT, tyrosine hydroxylase, GABA, 5-HT, Leu-enkephalin, and somatostatin. A dose of 50 nmol ECMA caused a prolonged 70% depletion of CAT activity and a 40% depletion of AChE activity. The other biochemical parameters were unchanged. This result corresponds to the morphological finding that 2 populations of cholinergic cells were destroyed and that the AChE activity associated with their terminal arbors was lost. A third population of cholinergic cells, located towards the middle of the inner nuclear layer, was resistant to the toxic effects of ECMA. The other cell types, except for somatostatin-immunoreactive cells and photoreceptors, which showed transient effects, were unaffected. ECMA therefore appears to be a highly specific toxin for cholinergic cells in the retina. PMID- 2880937 TI - Glutamate neurotoxicity in cortical cell culture. AB - The central neurotoxicity of the excitatory amino acid neurotransmitter glutamate has been postulated to participate in the pathogenesis of the neuronal cell loss associated with several neurological disease states, but the complexity of the intact nervous system has impeded detailed analysis of the phenomenon. In the present study, glutamate neurotoxicity was studied with novel precision in dissociated cell cultures prepared from the fetal mouse neocortex. Brief exposure to glutamate was found to produce morphological changes in mature cortical neurons beginning as quickly as 90 sec after exposure, followed by widespread neuronal degeneration over the next hours. Quantitative dose-toxicity study suggested an ED50 of 50-100 microM for a 5 min exposure to glutamate. Immature cortical neurons and glia were not injured by such exposures to glutamate. Uptake processes probably do not limit GNT in culture, as the uptake inhibitor dihydrokainate did not potentiate GNT. Possibly reflecting the lack of uptake limitation, glutamate was found to be actually more potent than kainate as a neurotoxin in these cultures, a dramatic reversal of the in vivo potency rank order. Some neurons regularly survived brief glutamate exposure; these possibly glutamate-resistant neurons had electrophysiologic properties, including chemosensitivity to glutamate, that were grossly similar to those of the original population. PMID- 2880938 TI - Ionic dependence of glutamate neurotoxicity. AB - The cellular mechanisms by which excess exposure to the excitatory neurotransmitter glutamate can produce neuronal injury are unknown. More than a decade ago it was hypothesized that glutamate neurotoxicity (GNT) is a direct consequence of excessive neuronal excitation ("excitotoxicity" hypothesis); more recently, it has been hypothesized that a Ca influx triggered by glutamate exposure might mediate GNT (Ca hypothesis). A basic test to discriminate between these hypotheses would be to determine the dependence of GNT on the extracellular ionic environment. The excitotoxicity hypothesis predicts that GNT should depend critically on the presence of extracellular Na, since that ion appears to mediate glutamate neuroexcitation in the CNS; the Ca hypothesis predicts that GNT should depend critically on the presence of extracellular Ca. The focus of the present experiments was to determine the effects of several alterations in the extracellular ionic environment upon the serial morphologic changes that occur after mouse neocortical neurons in cell culture receive toxic exposure to glutamate. The results suggest that GNT in cortical neurons can be separated into 2 components distinguishable on the basis of differences in time course and ionic dependence. The first component, marked by neuronal swelling, occurs early, is dependent on extracellular Na and Cl, can be mimicked by high K, and is thus possibly "excitotoxic." The second component, marked by gradual neuronal disintegration, occurs late, is dependent on extracellular Ca, can be mimicked by A23187, and is thus possibly mediated by a transmembrane influx of Ca. While either component alone is ultimately capable of producing irreversible neuronal injury, the Ca-dependent mechanism predominates at lower exposures to glutamate. Glutamate exposure likely leads to a Ca influx both through glutamate-activated cation channels and through voltage-dependent Ca channels activated by membrane depolarization. Addition of 20 mM Mg, however, did not substantially block GNT; this finding, together with the observation that GNT is largely preserved in sodium-free solution, supports the notion that the activation of voltage dependent Ca channels may not be required for lethal Ca entry. The possibility that N-methyl-D-aspartate receptors may play a dominant role in mediating glutamate-induced lethal Ca influx is discussed. PMID- 2880939 TI - Synaptic functions in rat sympathetic neurons in microcultures. IV. Nonadrenergic excitation of cardiac myocytes and the variety of multiple-transmitter states. AB - In the first 3 papers of this series (Furshpan et al., 1986a, b; Potter et al., 1986), a sensitive microculture procedure was used to show that sympathetic principal neurons, dissociated from newborn or adult superior cervical ganglia and grown singly on cardiac myocytes, display adrenergic, cholinergic, and purinergic functions, sometimes in isolation but more often in combination. In this paper we describe additional effects on cardiac myocytes evoked by these neurons; the effects were excitatory and insensitive to adrenergic blocking agents (and to agents that block the inhibitory effects of acetylcholine and purines). In some of these microcultures, evidence consistent with secretion of serotonin was obtained; the nonadrenergic excitatory effect was diminished or abolished by serotonin blockers or reserpine. Further evidence for serotonergic transmission is presented in the accompanying paper by Sah and Matsumoto (1987). In other cases, an as-yet-unidentified agent "X" also produced a nonadrenergic excitation. The X effect characteristically required a prolonged train of neuronal impulses, had a time course of 50-200 sec, and was insensitive to agents that affected the other transmitters, including serotonin. In addition, we discuss 2 remarkable features of the transmitter repertoire of the microcultured sympathetic neurons: expression of the several transmitters in a variety of combinations, including at-least-quadruple function, and expression of the transmitters within a particular combination in varying relative strengths. The result is a diversity of transmitter release greater than that previously reported for vertebrate or invertebrate neurons. PMID- 2880940 TI - Proctolin in identified serotonergic, dopaminergic, and cholinergic neurons in the lobster, Homarus americanus. AB - In order to explore the functions of the peptide proctolin in the lobster nervous system, 3 classes of neurons showing proctolin-like immunocytochemical staining were selected for study. These neurons were identified on the basis of physiological and/or morphological criteria, isolated by dissections, and analyzed with biochemical methods to determine whether they contained authentic proctolin and which classical neurotransmitters coexisted with the peptide. Pairs of large proctolin-immunoreactive neurons in fifth thoracic and first abdominal ganglia were identified as serotonin-immunoreactive neurons (Beltz and Kravitz, 1983, 1987) by staining serial sections of the ganglia alternately with the 2 antisera. Physiologically identified cells, dissected from the ganglia and analyzed with high-performance liquid chromatography (HPLC), contained approximately 20 microM proctolin and 0.5 mM serotonin. A large proctolin immunoreactive neuron in the circumesophageal ganglion was identified as the lobster homolog of a dopaminergic neurosecretory cell found in other crustaceans (Cooke and Goldstone, 1970). The large lobster cell stained with antityrosine hydroxylase antiserum, and synthesized 3H-dopamine from 3H-tyrosine. Dissected cell bodies, analyzed by HPLC, contained approximately 25 microM proctolin. Proctolin-immunoreactive sensory neurons were identified as large stained fibers that terminated in sensory dendrites of the oval organ mechanoreceptor in the scaphognathite (Pasztor, 1979; Pasztor and Bush, 1982). The largest sensory fiber was isolated for biochemical studies. It synthesized 3H-acetylcholine from 3H choline and, by HPLC analysis, was found to contain approximately 3 microM proctolin. Thus, proctolin coexists with different conventional transmitters in several classes of identified lobster neurons. Investigations of the actions of proctolin in these different contexts should contribute to a more complete understanding of the diverse functions of neuropeptides and their roles as cotransmitters. PMID- 2880941 TI - Development of neurotransmitter metabolism in embryos of the leech Haementeria ghilianii. AB - We have investigated the development of neurotransmitter metabolism in embryos of the glossiphoniid leech Haementeria ghilianii. The neurotransmitter content of dissected embryonic tissues was measured by means of radioenzymatic assays, while the presence of neurotransmitters in individual identified neurons was detected by means of immunocytochemical and monoamine histofluorescence techniques. The capacity for synthesis of neurotransmitters was measured by incubating dissected embryonic tissues in radiolabeled neurotransmitter precursors. A specific neurotransmitter uptake system present in some neurons was detected by means of an autoradiographic technique. At an early stage of development of the nervous system, when most neurons are just beginning process outgrowth, the nerve cord acquires the capacity to synthesize ACh, 5-HT, and GABA from their immediate precursors, and contains ACh. Moreover, 5-HT-immunoreactive neurons and neurons that are capable of GABA uptake can be identified. Dopamine-containing neurons are first detected by their histofluorescence at a slightly later stage, after process outgrowth is under way. As development continues, the content of and capacity for synthesis of these neurotransmitters increase, as does the number of neurons capable of GABA uptake. During the earlier stages of development, ACh content exceeds 5-HT content, which in turn exceeds dopamine content. By the end of embryogenesis, however, 5-HT and dopamine contents have greatly increased relative to ACh content, with 5-HT content exceeding ACh content by a factor of 2. Of the neurotransmitters thus far studied, 5-HT is present in the highest amount in the juvenile and adult nerve cord. Our results indicate that in the development of the leech nervous system neurotransmitter metabolism is one of the first neuronal characters to differentiate and that the subsequent levels of the different neurotransmitters are differentially regulated. PMID- 2880942 TI - MDMA (3,4-methylenedioxymethamphetamine): proceedings of the conference. May 17 18, 1986, Oakland, California. PMID- 2880943 TI - The background and chemistry of MDMA. PMID- 2880944 TI - Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens. PMID- 2880945 TI - The biology of human information processing. PMID- 2880946 TI - Subjective reports of the effects of MDMA in a clinical setting. PMID- 2880947 TI - Meetings at the edge with Adam: a man for all seasons? PMID- 2880948 TI - The psychological and physiological effects of MDMA on normal volunteers. AB - The experimental subjects were older than the average general population, more educated and considerably experienced in drug use. They considered themselves to have benefited by their MDMA experience, with no evidence of harm. There were moderate, consistent biochemical, cardiovascular and neurobehavioral changes within normal limits that peaked between one and two hours following ingestion, returning to predrug levels within 24 hours. This experimental situation produced no observed or reported psychological or physiological damage, either during the 24-hour study period or during the three-month follow-up period. While the subjects are not typical of the general population, the findings support the general impression among knowledgeable professionals that MDMA is reasonably safe, produces positive mood changes in users, does not cause negative problems (if used sparingly and episodically) and is without evidence of abuse. Certainly, any drug that causes ataxia, elevates blood pressure and pulse is potentially unsafe. One can say little about safety when effects and side effects are studied for only 24 hours and then a blood cytology is obtained after three months. In this study, safety must exclude long-term toxicity. Not enough is known about MDMA's long-range effects other than information from random anecdotal evidence supplied by a few clinicians plus self-reports by unselected and unsupervised users. From the information presented here, one can only say that MDMA, at the doses tested, has remarkably consistent and predictable psychological effects that are transient and free of clinically apparent major toxicity. The experimental subjects believed that MDMA is both safe and beneficial, but there is insufficient evidence to accurately judge either the drug's potential harm or benefit. PMID- 2880950 TI - MDMA. Nonmedical use and intoxication. PMID- 2880949 TI - MDMA. The dark side of ecstasy. PMID- 2880951 TI - MDMA and human sexual function. PMID- 2880952 TI - Some considerations on the prevalence of MDMA use. PMID- 2880953 TI - MDMA on the street: Analysis Anonymous. PMID- 2880954 TI - Controls over the manufacture of MDMA. PMID- 2880955 TI - MDMA reconsidered. PMID- 2880956 TI - Juvenile Graves disease: usefulness and limitations of thyrotropin receptor antibody determinations. AB - Thyrotropin receptor antibodies (TRAb) were measured in serum from 49 patients with active and inactive juvenile Graves disease, and the results were compared with values from control subjects and patients with Hashimoto disease. With a thyrotropin binding inhibition immunoglobulin (TBII) assay, TRAb were found in serum from 25 (93%) of 27 patients with untreated, active Graves disease. The TRAb values remained positive in 20 (72%) of 29 patients during the first 6 months of antithyroid therapy and in 13 (54%) of 24 patients during the second 6 months. After discontinuation of antithyroid therapy, 15 patients experienced 18 episodes of relapse of thyrotoxicosis; during relapse TRAb values were positive in all but one patient. Among 19 patients who remained clinically and biochemically euthyroid after cessation of antithyroid therapy, TRAb were not detected in 28 (78%) of 36 serum specimens. Of the eight positive values from six patients, no antiidiotypic antibodies were found, and thyroid stimulating immunoglobulins (TSI) were not detected in four specimens. The TRAb determination correctly predicted the subsequent clinical course in 26 (72%) of 36 patients. Furthermore, TRAb values and results of triiodothyronine suppression tests were in agreement in 27 of 36 patients, or 75% of the time. TSI were present in serum from only 19 (73%) of 26 patients with active disease; however, TSI were negative in all patients with inactive Graves disease. During the management of Graves disease, TRAb measurements by TBII determinations are valuable in the diagnosis of active disease, assist in the decision to discontinue antithyroid drug therapy, and are useful as the T3 suppression test to predict the clinical course of the disease. The TSI measurement is most useful to determine the activity of the disease when TRAb values are positive in a euthyroid patient. PMID- 2880957 TI - The nature of the oil phase and the release of solutes from multiple (w/o/w) emulsions. AB - The effect of the nature of the oil phase of w/o/w emulsions stabilized by interfacial complexation between span 80 (sorbitan mono-oleate) and albumin has been studied. The long-term stability of the systems has been assessed by photomicrography and by measuring the quantity of an internal marker (NaCl) remaining entrapped with time. The number of multiple oil drops and the diameters of the internal aqueous droplets were determined over 6 weeks, and the amounts of NaCl entrapped over the same period were followed. There were no significant changes in w/o/w emulsions prepared with a range of hydrocarbons (octane, dodecane, hexadecane, toluene and cyclohexane), indicating stable multiple emulsions. The release of NaCl and 5-fluorouracil (5-FU) separately entrapped in the internal aqueous phase of w/o/w emulsions was measured. Diffusion of the un ionized species of 5-FU across the oil phase or through localized thin oil lamellae is the primary transport mechanism. In the presence of surface active agents, water is solubilized in inverse micelles which would possess the ability to solubilize other water-soluble components, such as NaCl and 5-FU. The mixed inverse micellar units of Span 80 and polysorbate (Tween) 80 therefore act as solute carriers across the liquid hydrocarbon membrane separating the two aqueous phases of the emulsions. The main factor in determining the differences in rates of release from the hydrocarbon emulsions appears to be the droplet size of the internal aqueous phase. PMID- 2880958 TI - Ultrasonically mediated solute permeation through polymer barriers. AB - The effects of ultrasound on the permeation of benzoic acid through polydimethylsiloxane, and hydrocortisone through cellulose was investigated. Ultrasonic irradiation resulted in a 23% increase in the permeability coefficient of hydrocortisone in a cellulose film. A 14% increase in permeability coefficient was observed for benzoic acid in a polydimethylsiloxane film. The effects of ultrasound on stagnant aqueous diffusion layers, membrane-solution interfacial temperature, membrane integrity, and diffusant stability were investigated. These factors were not responsible for the observed increases in permeability. PMID- 2880959 TI - A platelet-aggregating and hypotensive phospholipid isolated from bovine brain. AB - A phospholipid that differs from known active lipids and causes potent platelet aggregation and weak hypotension has been isolated from bovine brain. Its platelet aggregating effect on heparinized platelet-rich plasma from rabbits, was at a threshold concentration of about 0.2 nmol ml-1 as phosphorus. The effect was inhibited by CV-3988. The phospholipid was converted by diazomethane treatment to another active lipid that caused short-term hypotension, but not platelet aggregation, rather it inhibited the aggregation of rabbit heparinized platelets induced by platelet-activating factor. PMID- 2880960 TI - Antipyrine kinetics following partial blood exchange with Fluosol-DA in the rat. AB - The effects of partial blood exchange with Fluosol-DA on hepatic microsomal oxidative metabolism have been studied in the rat. Antipyrine clearance (Cl) was used as an in-vivo measure of the activity of the mixed function oxidase system. Rats were partially exchanged with Fluosol-DA and dosed with antipyrine at selected time intervals following exchange. No change in antipyrine Cl was observed at 0.5 h, but there was a statistically significant decrease at 24 h and then an increase by more than 50% relative to control at 48 and 72 h. These data indicate that the effects of Fluosol-DA on hepatic function are time-dependent and that Fluosol-DA has the potential both to inhibit and to enhance hepatic metabolism. The possibility of altered hepatic metabolism should be considered when patients transfused with Fluosol-DA are given drugs primarily metabolized by the mixed function oxidase system. PMID- 2880961 TI - Comparison of bioavailability in man of tamoxifen after oral and rectal administration. AB - The bioavailability of tamoxifen from 40 mg suppositories was tested in six male volunteers and compared with that of tamoxifen (Nolvadex) tablets. Plasma concentrations of tamoxifen and its major metabolites, 4-hydroxytamoxifen and N desmethyltamoxifen, were measured by extraction from plasma obtained at different times after administration, separated by HPLC, converted on-line to fluorescent phenanthrene derivatives and quantified with a fluorescence detector. The mean relative bioavailability from the suppositories was 28%; the addition of a surfactive agent diminished the bioavailability to 13%. Simulation of repeated administration of 40 mg suppositories suggests a mean steady state plasma concentration for tamoxifen of approximately 70 ng ml-1, i.e. 30% of the steady state value after simulated oral administration. Rectal administration of tamoxifen leads to a lower bioavailability than that by oral administration and therefore cannot be recommended when used in equivalent doses. PMID- 2880962 TI - The use of [3H]vasopressin for in-vivo studies of controlled delivery from an Accurel/collodion device in the Brattleboro rat. AB - Accurel polypropylene/collodion controlled drug-delivery devices containing 22 micrograms [3H]vasopressin (VP) were implanted s.c. in VP-deficient Brattleboro rats. This caused a decrease in their urine production for at least 50 days, at which time the Accurel device was removed. Release of VP was followed by measurements of tritium radioactivity and by radioimmunoassay of VP in the urine. These parameters showed a constant pattern during the whole period. After re implantation of the Accurel devices in another group of Brattleboro rats, release of VP continued to give the same level of urine production as during the last period of the first implantation. It is concluded that release of VP in-vivo is not influenced by encapsulation of the Accurel polymer by connective tissue, or that adaptation of the kidney adds to the maintenance of the urine production at this low level. In-vivo release rate is calculated to be about 1% of the original load each day. The in-vitro release in a flow cell system appeared to produce the same release rate which indicates that these data have a predictive value for the in-vivo situation. PMID- 2880963 TI - Investigation of the antimuscarinic and other actions of proadifen in-vitro. AB - The possibility that proadifen (SKF 525A) antagonizes endothelium-dependent relaxations to acetylcholine (ACh) in isolated blood vessel preparations via a muscarinic receptor blocking action has been investigated. In phenylephrine contracted rat isolated aortic ring preparations (with endothelium), proadifen (10-100 microM) shifts ACh relaxant curves to the right without affecting the maximal response, yet endothelium-dependent relaxations to ATP are unaffected. At lower concentrations, proadifen (1-10 microM) antagonizes negative inotropic responses to ACh and ATP in guinea-pig left atria, antagonizes contractile responses to ACh and elevated [K+] in guinea-pig ileal preparations, displaces ( )-[3H]quinuclidinyl benzilate from muscarinic binding sites in membrane homogenates of guinea-pig ileal longitudinal muscle and reduces contractile responses to elevated [K+] in rat aortic ring preparations. It is concluded that proadifen may possess complex interactions with muscarinic receptors and Ca2+ entry blocking properties in concentrations 10-100 times lower than those reported to inhibit cytochrome P450-catalysed reactions. PMID- 2880965 TI - [3H]SCH 23390 identifies D-1 binding sites in rat striatum and other brain areas. AB - The specific in-vitro binding of [3H]SCH 23390 has been characterized and its use in the identification of D-1 sites in various brain regions examined. At a single ligand concentration (0.4 nM) the specific binding of [3H]SCH 23390 to striatal membranes was routinely 98% of total binding as defined using 10(-5) M cis flupenthixol. Specific binding at 37 degrees C reached equilibrium at 15 min and was reversible with a t1/2 for dissociation of 14 min. Specific binding of [3H]SCH 23390 over a range of concentrations (0.01-3.5 nM) was saturable (Bmax 73 pmol g tissue-1) of high affinity (Kd 0.36 nM) and to a single population of binding sites. Specifically bound [3H]SCH 23390 (0.4 M) was stereo selectively displaced by the isomers of butaclamol and flupenthixol but not by the D-2 selective antagonist, sulpiride. 5-HT, noradrenaline and cinanserin caused little or no displacement. Specific binding of [3H]SCH 22390 (0.4 nM; as defined using 10(-5) M cis-flupenthixol) showed marked regional variation. Specific binding was highest in the striatum; high levels were also observed in the mesolimbic area and substantia nigra. Lower specific binding was found in the frontal cortex and superior colliculus with the lowest levels in cerebellar preparations. The inclusion of 3 X 10(-7) M cinanserin did not alter the extent of specific binding observed in any brain region. The properties of [3H]SCH 23390 suggest it to be an excellent ligand for identification of D-1 sites in a variety of brain regions. PMID- 2880964 TI - Calculated and actual changes in beta-adrenoceptor number associated with increases in rat and guinea-pig cardiac sensitivity. AB - Chronic catecholamine depletion induced by reserpine pretreatment of rats, or 6 hydroxydopamine pretreatment of guinea-pigs, resulted in an enhanced sensitivity of isolated papillary muscles to isoprenaline. This hypersensitivity was accompanied by 1.41-(rats) and 1.52-fold (guinea-pigs) increases in the number of [3H]dihydroalprenolol binding sites, without changes in binding affinity. An equation was derived for calculation of increases in receptor number. Application of this showed that substantially greater increases in receptor number were required (2.32- to 4.04-fold) to account for the degree of supersensitivity observed. PMID- 2880966 TI - N-formylpenicillamine and penicillamine as degradation products of penicillins in solution. AB - The degradation of several penicillins in unbuffered aqueous solution produces N formylpenicillamine, in some cases in high yield. Very little or no penicillamine is formed under these conditions. N-Formylpenicillamine was produced from benzylpenicillin at pH values between 2.5 and 7, with a maximum yield of 30% at pH 5, whereas penicillamine was produced only at pH 5 or below in a yield of less than 1%. Benzylpenicillenic acid at pH 5 gave a 20% yield of N formylpenicillamine and no penicillamine whereas benzylpenicilloic, penilloic and penillic acids gave no N-formylpenicillamine and a small amount of penicillamine. PMID- 2880967 TI - Determination of cotinine in biological fluids of non-smokers by packed column gas-liquid chromatography. AB - A method is described for the analysis of cotinine in plasma, saliva and urine using packed-column gas-liquid chromatography, which is sufficiently sensitive and reproducible for quantitative study of the low levels resulting from exposure of non-smokers to other people's smoke. The lower limit of detection of cotinine in these fluids was 100 pg ml-1. The coefficient of variation over the range 0.25 to 2.0 ng ml-1 averaged 7.7%. In a sample of 85 non-smokers the concentrations of cotinine in plasma correlated 0.82 with those in urine and saliva, while the correlation between the saliva and urine concentrations was 0.91. Saliva cotinine concentrations were quantitatively related to passive exposure to parental smoking in a population study of 569 non-smoking schoolchildren. PMID- 2880968 TI - Acute effect of nicotine on the striatal dopaminergic system in the rat. AB - The acute effects of nicotine (1.5 mg kg-1 day-1) on the striatal dopaminergic system have been examined in the rat. Twenty-four hours after nicotine treatment, spontaneous locomotor activity in response to apomorphine or (+)-amphetamine and the binding of [3H]spiperone to striatal particulates were determined. Pretreatment of nicotine did not alter the characteristics of [3H]spiperone binding to striatal dopamine receptors. The nicotine treatment did not affect the apomorphine-induced locomotor activity, however, the (+)-amphetamine-stimulated locomotor activity was attenuated. These results suggest that nicotine acutely alters the presynaptic dopaminergic activity without significantly affecting the postsynaptic dopaminergic function. PMID- 2880969 TI - The effect of sodium deoxycholate given by gavage with heparin on the histology of the intestinal mucosa of the rat. AB - To gain direct insight into the mechanism of sodium deoxycholate (DOC)-induced enhancement of gastroenteral heparin absorption in rats, we performed light and electron microscopic examination of the mucosa of the small intestine of animals treated orally with DOC, heparin or DOC plus heparin. The sole morphological change observed after DOC and DOC plus heparin administration was a marked reduction in the length and distribution of glycocalyx filaments on the microvilli of epithelial cells. The morphological picture had reverted to normal after 24 h, when the promotion of enteral heparin absorption by DOC is greatly reduced. Thus, we suggest that DOC may promote the enteral absorption of heparin in rats by affecting some as yet unidentified barrier mechanism requiring glycocalyx integrity. PMID- 2880970 TI - On the binding of cinmetacin and indomethacin to human serum albumin. AB - The binding of two non-steroidal anti-inflammatory drugs, indomethacin and cinmetacin, to human serum albumin was studied by dynamic dialysis at 37 degrees C and pH 7.4. Cinmetacin is bound more than indomethacin. The affinity constant for the primary binding site is 4.28 X 10(6) M-1 for cinmetacin and 1.4 X 10(6) M 1 for indomethacin. The protein binding of indomethacin is decreased in the presence of cinmetacin. PMID- 2880971 TI - Disposition of aprophen in rats. AB - The pharmacokinetics of [14C]aprophen and its distribution were determined after intravenous administration to rats. The drug was distributed rapidly with a t1/2 (alpha) of 4 min to highly perfused organs like the brain, kidney and adrenals. An elimination phase was apparent 10 min after injection with a t1/2 (beta) of 23.5 min. The high plasma clearance of the drug was due both to a large volume of distribution and to a high metabolic rate. Aprophen could be hydrolysed to diphenylpropionic acid and diethylaminoethanol in-vivo and in-vitro. Diethylaminoethanol competed with [3H]QNB binding to muscarinic receptors of N4TG1 cells, whereas diphenylpropionic acid did not. The lower plasma concentrations and lower binding activity of diethylaminoethanol compared with aprophen indicate that unchanged aprophen is largely responsible for the in-vivo actions. PMID- 2880972 TI - Tolerance to the anticonvulsant effect of clonazepam in mice: no concurrent change in plasma concentration. AB - Clonazepam was administered for 10 or more days on three different dose regimens (0.5, 0.25 and 0.08 mg kg-1 twice daily) to mice given pentetrazol by slow intravenous infusion. Plasma concentrations of clonazepam were assayed by high performance liquid chromatography. Tolerance developed to the anticonvulsant effect of clonazepam at all doses but was incomplete and could be overcome by increasing the dose. With the 0.5 and 0.25 mg kg-1 regimens there was no significant change in the drug plasma concentrations during development of tolerance; on the lowest dose, levels were below the limits of accurate detection. Anticonvulsant tolerance does not seem to be the result of a disturbance in clonazepam metabolism. PMID- 2880973 TI - Functional evidence for altered activity of GABAergic receptors following chronic desipramine treatment in rats. AB - The antinociceptive effect of subcutaneous 4,5,6,7-tetrahydroisoxazol[5,4 c]pyridin-3-ol (THIP) or (+/-)-baclofen, measured as reaction time of rats placed on a plate heated to 55 degrees C, was assessed after a single or the last repeated (18 consecutive days) dose (5 mg kg-1 once daily) of subcutaneous desipramine. Baclofen (10 mg kg-1)-induced antinociception was reduced by acute and unaffected by chronic desipramine treatment. On the contrary, THIP (20 mg kg 1)-induced antinociception was unaffected by acute and reduced by chronic desipramine. PMID- 2880974 TI - Early inflammatory response to carrageenan in the pleural cavity and paw of rats with altered body temperature. AB - Polymorphonuclear leucocyte (PMNL) migration and oedema induced by carrageenan in the pleural cavity and paw, respectively, of rats made hyper- or hypothermic by physical and chemical means have been investigated. In rats placed in a warm environment to produce a rise in body temperature, carrageenan caused a moderate but significant increase in PMNL migration compared with the control animals. Opposite effects were obtained with hypothermic animals kept in a cold environment. While hyperthermia produced by amphetamine did not alter the PMNL migration, chlorpromazine-induced hypothermia caused a fall in the number of these cells present in the pleural cavity following carrageenan. Both hyper- and hypothermias, whether induced by physical or chemical means, inhibited the carrageenan paw oedema. The observed changes in the PMNL numbers in the pleural cavity did not reflect their numbers in the peripheral circulation. Results indicate that while a rise or a fall in body temperature may have opposite effects on PMNL migration, in carrageenan inflammation both conditions inhibit oedema formation. PMID- 2880975 TI - The influence of degradable starch microspheres on liver uptake of 5-fluorouracil after hepatic artery injection in the rat. AB - The effect of degradable starch microspheres (DSM) on the distribution of 5 fluorouracil (5-FU) after hepatic artery injection was studied in normal rats. Carbon-14-labelled 5-FU was injected separately or together with DSM into the hepatic artery. Radioactivity was measured in liver tissue, bile, peripheral blood, and urine. When microspheres were added, the liver uptake of 5-FU was increased; its peak concentration in peripheral blood decreased, as did the early urinary excretion of radioactivity. The addition of degradable starch microspheres to hepatic artery injections of cytostatic drugs might be of value in increasing the drug concentration in tumour tissue and reducing systemic toxicity. PMID- 2880976 TI - Some factors affecting the release of imipramine from gel-precipitated aluminium hydroxide spheres. AB - Changing the pH of the dissolution medium has been found to affect the release of imipramine from gel-precipitated aluminium hydroxide spheres. Release from unwashed, unheated spheres into solutions of pH 1.2 was controlled by dissolution of the gel matrix, whereas that into solutions of pH 3 and pH 5 appeared to be under diffusion control. The liberation of drug from unwashed, heated spheres into the media of higher pH exhibited more complex kinetics. Washed spheres failed to release significant amounts of imipramine into the solutions of pH 3 and 5. Changing the ionic strength of the media had little effect on drug release. These phenomena have been explained with reference to model theories of the precipitation and ageing of aluminum hydroxide gels and their pH-solubility profiles. PMID- 2880977 TI - Changes in glutathione and its metabolizing enzymes in human erythrocytes and lymphocytes with age. AB - The levels of glutathione (GSH) and the activities of glutathione S-transferases (GST) and glutathione reductase (GSR) in human erythrocytes and lymphocytes were determined in three age groups (5-12, 25-40, 65-83 years). The levels of GSH in lymphocytes increased with age, however, its levels in erythrocytes reached a maximum in the middle age group. The activity of GST in erythrocytes and lymphocytes changed as a function of age in a pattern similar to the changes found for GSH levels. GSR activity increased from young to middle age in both erythrocytes and lymphocytes, but decreased again in the old age group. PMID- 2880978 TI - Identification of two metabolites of the cholinesterase reactivator HI-6 isolated from rat urine. AB - Two metabolites, isolated from the urine of rats given the cholinesterase reactivator HI-6 intravenously, still contained quaternary nitrogen atoms and therefore could not be extracted from aqueous solutions by organic solvents. Both metabolites were isolated by preparative high performance liquid chromatography and were identified using mass spectrometry, gas chromatography, infrared spectrometry, ultraviolet spectrometry and proton nuclear magnetic resonance spectrometry. The structures were confirmed by in-vitro preparation of the compounds. both metabolites contained 2-pyridone moieties. One had an intact pyridinium-aldoxime moiety, and therefore could still be therapeutically active. The excretion of unchanged HI-6 together with the two identified metabolites does not provide for a 100% mass balance, indicating that in the rat, other, as yet unidentified, metabolites must be formed. PMID- 2880979 TI - In-vivo studies of amphotericin B liposomes derived from proliposomes: effect of formulation on toxicity and tissue disposition of the drug in mice. AB - The repeat dose toxicity of various liposomal formulations containing amphotericin B has been determined in mice. In general, small liposomes (e.g. 100 150 nm) were found to be more toxic than their large counterparts (e.g. about 2000 nm). However, the repeat dose toxicity of small liposomes could be diminished substantially by the inclusion of sterol (i.e. ergosterol) into the liposomal membranes. Tissue accumulation studies of amphotericin B after repeat dosing may be a useful adjunct to formulation development. PMID- 2880980 TI - Central dopamine receptors and their role in digoxin-induced cardiotoxicity in the dog. AB - The role of the dopaminergic system in digoxin-induced cardiotoxicity has been examined. Specific dopaminergic agonists and antagonists were administered into the ventriculocisternal system of pentobarbitone-anaesthetized dogs before systemic administration of digoxin. Pretreatment with apomorphine, a specific dopamine agonist, did not significantly alter the arrhythmogenic or lethal doses of digoxin. However, the digoxin-induce increase in CSF noradrenaline was decreased significantly in apomorphine-pretreated animals. Pretreatment with pimozide, a specific dopamine antagonist, significantly decreased the arrhythmogenic dose of digoxin but did not alter the lethal dose. As with apomorphine, pimozide-pretreated animals accumulated significantly less noradrenaline in CSF compared with control dogs. These results suggest that dopamine receptors are not directly related to the cardiotoxic actions of digoxin. However, dopaminergic receptors may influence the balance of central catecholaminergic systems that influence the peripheral cardiovascular system. PMID- 2880981 TI - Experimental pharmacological study of moroxybrate, a hypolipidaemic, antithrombotic, antiatheromatous agent. AB - Moroxybrate, a drug obtained by the reaction of clofibric acid with moroxydine, a biguanide with practically no effect on carbohydrate metabolism, has been examined for its effects on blood lipids, fibrinogen, in-vitro platelet aggregation, and also on experimental atherosclerotic lesions obtained by feeding the rabbits a diet containing 1% cholesterol. At the same dose, moroxybrate has an effect at least equal to those of clofibrate and moroxydine alone, on the lipidic parameters and haemostasis in rat and rabbit. The combination of these actions together with an effect on the prevention of experimental atherosclerosis lesions in the rabbit suggests moroxybrate should be examined for its effects in ischaemic cardiovascular disease. PMID- 2880982 TI - The antagonistic effect of morphine on rhein-stimulated fluid, electrolyte and glucose movements in guinea-pig perfused colon. AB - Rhein (1,8-dihydroxy-3-carboxyanthraquinone), in a concentration of 6 X 10(-4)M, inhibits water absorption from the colon and causes a net transfer of fluid and electrolyte into the intestinal lumen. Morphine (4 X 10(-4)M) counteracted the water and electrolyte secretion. Prior perfusion with morphine protected the large intestine from the laxative effect of a rhein perfusion. Differences in absorption rate of 99mTc-EDTA, a poorly absorbable marker, were found, as morphine caused nearly all radioactive compound to be retained in the colon, while rhein significantly facilitated the transfer of marker from colon through mucosal barrier to blood. The route followed by the 99mTc-EDTA complex was not the same as that followed by water, suggesting that 99mTc-EDTA travels by a paracellular route. Morphine counteracted the inhibition of Na+ absorption caused by rhein and antagonized the massive loss of K+ incurred by the presence of rhein in the colon. Cl- absorption is reversed to secretion in the presence of rhein while normal values were restored by morphine. Neither the HCO-3 content nor the pH were affected by either drug. Active absorption of glucose was completely blocked in the presence of rhein; the block could be antagonized by morphine. PMID- 2880983 TI - Solubilization kinetics of n-alkanes by a non-ionic surfactant. AB - The rates of solubilization of a homologous series of n-alkanes (CnH2n + 2; n = 8 16) into micellar solutions of n-dodecyl hexaoxyethylene glycol ether (C12E6) have been measured at 298 K. A mechanism involving a micellar dissociation association process previously proposed was found to give an adequate description of the data. Proportionality between the micellar solubilization capacity in the kinetic process and that found at equilibrium could be inferred for such a series of solubilizates which have the same locus of solubilization and packing requirements. PMID- 2880984 TI - The effect of polycarbophil on the gastric emptying of pellets. AB - The influence of the putative bioadhesive, polycarbophil, on the gastric emptying of a pellet formulation, has been investigated in three fasted subjects. The pellets were radiolabelled with technetium-99m. Gastric emptying was measured using the technique of gamma scintigraphy. The pellets emptied from the stomach rapidly and in an exponential manner. Polycarbophil did not retard the gastric emptying of the pellets. PMID- 2880985 TI - Liquid chromatographic determination of ampicillin and its metabolites in human urine by postcolumn alkaline degradation. AB - A high-performance liquid chromatographic method has been developed for the determination of ampicillin (I) and its metabolites [5R,6R)-penicilloate (II), the (5S,6R)-epimer (III), and piperazine-2,5-dione (IV)) in human urine. The assay was based on the measurement of the absorbance at 300 nm following the postcolumn alkaline degradation with 0.75 M sodium hydroxide, 2 X 10(-3) M mercuric chloride, and 1 X 10(-2) M ethylenediaminetetraacetic acid disodium salt in solution. The limits of accurate determination were 0.5 microgram mL-1 for I, 2.0 microgram mL-1 for II and III, and 1.0 microgram mL-1 for IV in neat urine samples with a 10 microL injection. At concentrations of compounds I-IV of 5 micrograms mL-1, within- and between-run precisions were 1.10-4.03% and 0.93 2.34%, respectively. The urinary levels of I and its metabolites were quantified by the proposed method. PMID- 2880986 TI - A quantitative assessment of the reactivity of the fatty alcohols with cetrimide using immersion calorimetry. AB - The reactivity of the fatty alcohols with cetrimide has been quantitatively assessed using immersion calorimetry. In all cases the reaction was endothermic i.e. it had a positive enthalpy. For the n-alcohols the reactivity, as evaluated by the rate of enthalpy change, decreased with increasing chain length although branching on the tetradecanol and hexadecanol resulted in a higher reactivity. Adding 1-octadecanol to 1-hexadecanol resulted in an increased reactivity rising to a maximum for mixtures containing 20-40% w/w 1-octadecanol. The results have been interpreted in terms of the polymorphic form of the alcohol. PMID- 2880987 TI - Lipid vehicles for intestinal lymphatic drug absorption. AB - The lipoprotein fractions in mesenteric lymph were monitored following intraduodenal administration of arachis oil and oleic, linoleic and linolenic fatty acids to rats. An increase in the chylomicron fraction, but not the VLDL or LDL fraction, was observed with each lipid. The greater the degree of unsaturation of the fatty acid, the more rapid the onset of chylomicron synthesis. The administration of linoleic acid and arachis oil produced the highest concentration of chylomicrons in the lymph. These results reflect differences in the rate of absorption and biochemical metabolism of the lipids and have implications for the selection of vehicles for the delivery of drugs by the lymphatic route. PMID- 2880988 TI - The topical anti-inflammatory effects of a topical preparation of meclofenamic acid on carrageenan-induced footpad swelling in mice. AB - A topical preparation of meclofenamic acid (Meclomen) was tested for anti inflammatory activity in a murine model of carrageenan footpad oedema. The preparation significantly inhibited swelling when applied to the carrageenan injected paw. Maximum inhibition was observed 4-5 h after carrageenan injection. The topical effects could not be attributed to systemic absorption because the preparation was more inhibitory when applied topically to the carrageenan injected paw than to a distant site or orally. PMID- 2880990 TI - Effects of dimethyl sulphoxide (DMSO) on aggregation of human blood platelets. AB - The effects were examined of the universal solvent dimethyl sulphoxide (DMSO) on human platelet aggregatory activity, in-vitro, of the endogenous mediators ADP, adrenaline, arachidonic acid, collagen and PAF-acether which are believed to play important roles in cardiovascular diseases in man. DMSO inhibited aggregation induced by all of the mediators in the order ADP greater than adrenaline = arachidonic acid = PAF-acether greater than collagen. Since DMSO is widely used as a solvent for drug substances, an awareness of its intrinsic activity in any such evaluations is essential. PMID- 2880991 TI - The effect of digoxin dosage on the digoxin-quinidine interaction in the bile duct-cannulated rat. AB - Pretreating anaesthetized bile duct-cannulated rats with 9 mg kg-1 quinidine significantly decreased the cumulative biliary excretion of digoxin and its metabolites after 10 or 100 micrograms kg-1 [3H]digoxin, although the effect was more marked in animals receiving the high dose of digoxin. In contrast, however, although quinidine pretreatment raised plasma radioactivity levels by 50-80% in animals given the higher dose of digoxin, no significant effect on circulating plasma levels was observed in rats receiving 10 micrograms kg-1 digoxin. Generally, quinidine had no statistically significant effect on other aspects of digoxin disposition, although with both digoxin doses there were trends towards a reduction in the direct intestinal secretion and urinary excretion of digoxin derived radioactivity with an increase in tissue levels of radioactivity (apart from the small intestine wall where concentrations were reduced). The radioactivity in the bile after 100 or 10 micrograms kg-1 digoxin comprised about 25 and 33% of digoxin and digoxigenin bis-digitoxoside, respectively, as well as appreciable amounts of the monodigitoxoside and a highly polar component. This metabolite profile was unaffected by quinidine. The influence of cardiac glycoside dosage shown by the present work indicates that the digoxin-quinidine interaction and possibly analogous interactions involving other cardiac glycosides, may not always be readily detectable from plasma concentration data. PMID- 2880989 TI - Effects of microiontophoretic pentobarbitone on conditioned inhibitions mediated by GABA-A receptors in the cuneate nucleus of the rat in-vivo. AB - We have studied the effects of microiontophoretic sodium pentobarbitone on the conditioned inhibition of the negative potential (N-wave) evoked in the cuneate nucleus of the rat bv electrical stimulation (5 V, 0.2 ms, 0.5 Hz) of the ipsilateral forepaw. Five- or seven-barelled micropipettes were used, the tip being placed at a depth of 600-900 micron below the dorsal surface of the medulla oblongata. The conditioned inhibition was elicited by a previous identical stimulus. When the interval between the stimuli is shorter than about 40 ms (short duration) the inhibition is thought to be mediated by gamma-aminobutyric acid (GABA), acting on GABA-A receptors. When it is longer (long duration conditioned inhibition) GABA-A receptors are not thought to be involved. Microiontophoretic sodium pentobarbitone potentiated both short (15 ms) and long (45 ms) duration conditioned inhibitions. The effect was current-dependent and appeared whether or not the first N-wave was depressed. Microiontophoretic application of (-)-bicuculline methiodide (a GABA-A antagonist) reduced the potentiation by pentobarbitone up to the basal inhibition when the interval between the stimuli was 45 ms or longer and to a greater extent when it was 30 ms or shorter. It seems likely that pentobarbitone prolongs the GABA-ergic mechanism which produces the short duration inhibition, making it visible with long stimulus intervals, super-imposed upon the normal long duration conditioned inhibition which is not potentiated by local pentobarbitone. PMID- 2880992 TI - Evidence for spare alpha 1-adrenoceptors for the accumulation of inositol phosphates in smooth muscle. AB - The accumulation of inositol phosphates (IP) in smooth muscle from rat vas deferens and caudal artery was maximally increased 3- to 4-fold in response to exposure of the tissues to 100 microM noradrenaline. Clonidine (up to 3 mM) was a partial agonist. Pretreatment of the tissues with the irreversible alpha adrenoceptor antagonist phenoxybenzamine (0.3-10 microM) shifted the noradrenaline concentration-response curve to the right before depressing the maximum. The maximum of the clonidine concentration-response curve was depressed without significant change in the EC50 by the same treatment. These data, which are most easily interpreted as demonstrating the presence of a receptor reserve for IP accumulation, are discussed. PMID- 2880993 TI - Inhibition of amphetamine-induced locomotor activity by S-(+)-apomorphine: comparison with the action of R-(-)-apomorphine. PMID- 2880994 TI - A highly sensitive HPLC method for the assay of propantheline used to measure its uptake by rat intestinal brush border membrane vesicles. AB - A simple, sensitive, high-performance liquid chromatographic method for propantheline has been developed. Propantheline was quantitatively hydrolysed into xanthene-9-carboxylic acid in neutral or alkaline medium and the hydrolysate assayed by reversed phase high-performance liquid chromatography. This method measured to 2 pmol per injection and was used to investigate the uptake of the drug by rat intestinal brush border membrane vesicles. Propantheline was highly bound to the membrane and this binding was inhibited to varying extents by several quaternary ammonium compounds. Mepenzolate and methylbenactyzium inhibited it significantly, and neostigmine, butylscopolamine and N methylnicotinamide inhibited it moderately. Choline, acetylcholine and thiamine had no effect. PMID- 2880995 TI - Structural-equation models of current drug use: are appropriate models so simple(x)? AB - The simplex and common-factor models of drug use were compared using maximum likelihood estimation of latent variable structural models in two samples: a sample of 226 high school students, using ratio-scale measures of current drug use, and a sample of 310 industrial workers and 811 college students, using ordinal-scale measures of current drug use. Latent variables of alcohol, marijuana, enhancer hard drugs, and dampener hard drugs were specified in a series of structural models. Contrary to previous findings with cumulative drug use data, the common-factor model provided a more acceptable representation of the observed current-use data than did the simplex model in both samples. In addition, the similarity of results across both of these samples supports recent contentions by Huba and Bentler (1982) that quantitatively measured variables are not necessarily superior to qualitative, ordinal indicators in latent variable models of drug use. PMID- 2880996 TI - Polyarteritis nodosa presenting as serous otitis media in a patient receiving hyposensitization therapy. AB - Polyarteritis nodosa was diagnosed in a patient one year after an episode of severe serous otitis media and 2 1/2 years after initiation of a 23 month course of hyposensitization therapy for nonseasonal rhinitis. Relationships among immunotherapy, otitis media and polyarteritis nodosa merit emphasis because their recognition may lead to early diagnosis. PMID- 2880998 TI - Transmission studies in mosquitoes (Diptera: Culicidae) with disseminated Rift Valley fever virus infections. PMID- 2880997 TI - Cholestasis and fatal agranulocytosis complicating sulfasalazine therapy: case report and review of the literature. AB - A 55-year-old woman with rheumatoid arthritis in overlap with polymyositis received sulfasalazine for control of synovitis. Cholestatic jaundice, fever, urticaria and agranulocytosis developed after 20 days of treatment and culminated in fatal adult respiratory distress syndrome secondary to Legionella pneumophila. The increasing use of sulfasalazine in the therapy of rheumatoid arthritis mandates that the clinician be aware of this idiosyncratic drug reaction. PMID- 2880999 TI - Hypersensitivity reactions and hematologic changes in sheep exposed to mosquito (Diptera: Culicidae) feeding. PMID- 2881000 TI - Ecological evidence against vertical transmission of eastern equine encephalitis virus by mosquitoes (Diptera: Culicidae) on the Delmarva Peninsula, USA. PMID- 2881001 TI - Alpha 2 adrenergic receptors in canine prostate: biochemical and functional correlations. AB - The sympathetic innervation of human prostate adenomas has been previously demonstrated using fluorescence microscopy and in vitro isometric studies. A clinical implication of these observations is that bladder outlet obstruction in men with benign prostatic hypertrophy may be subject to pharmacologic manipulation using adrenergic drugs. Randomized clinical trials have demonstrated the efficacy of alpha adrenergic antagonists for symptomatic BPH. We have previously characterized the alpha1 and alpha2 adrenergic receptors in the human prostate using [3H]prazosin and [3H]rauwolscine, respectively. The mean alpha1 and alpha2 receptor densities in the adenomas studied were equivalent. The effect of alpha2 adrenergic drugs on prostatic urethral pressure has not been examined in the human or in an animal model. In this study a canine model was used to define the effect of alpha2 drugs on prostatic urethral pressure. Intravenous administration of clonidine, a selective alpha2 agonist, resulted in a dose dependent increase in prostatic urethral pressure. The maximal increase in urethral pressure ranged between 18 to 30 cm. H2O. The maximal response to clonidine was approximately 50% less than the response to epinephrine, indicating that clonidine acts as a partial agonist. Pretreatment with yohimbine, a selective alpha2 adrenergic antagonist, abolished the effects of clonidine and epinephrine. The alpha2 adrenergic receptors were then studied in the canine prostates using [3H]rauwolscine. The equilibrium dissociation constant, Kd, ranged between 0.68 to 1.80 nM and the receptor density ranged between 14.8 to 69.3 fmol./mg. protein. The receptor density was homogeneous in specimens obtained from the proximal, midportion, and distal canine prostate suggesting that the effect of alpha2 drugs is not sphincter mediated. These in vitro and in vivo studies provide the basis for investigating the effects of alpha2 antagonists in men with symptomatic BPH. PMID- 2881002 TI - 'Eve' and 'Ecstasy'. A report of five deaths associated with the use of MDEA and MDMA. AB - 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy"), a synthetic analogue of 3,4 methylenedioxyamphetamine, has been the center of recent debate over its potential for abuse vs its use as a psychotherapeutic agent. Following its emergency classification in Schedule 1 by the Drug Enforcement Administration in 1985, 3,4-methylenedioxyethamphetamine (MDEA, "Eve") has appeared as MDMA's legal replacement. MDMA is thought to be safe by recreational users and by psychotherapists who support its use. The details of five deaths associated with the use of MDMA and MDEA are reported. In three patients, MDMA or MDEA may have contributed to death by the induction of arrhythmias in individuals with underlying natural disease. In another patient, use of MDMA preceded an episode of bizarre and risky behavior that resulted in accidental death. In another patient, MDMA was thought to be the immediate cause of death. Death as a consequence of the use of these drugs appears to be rare, but it does occur; this outcome may be more common in individuals with underlying cardiac disease. PMID- 2881003 TI - [Abnormalities in chromosome 12 of T cell malignancies]. PMID- 2881004 TI - [Smoldering ATL appeared in the course of collagen disease-like symptoms. Followed by the crisis and death]. PMID- 2881005 TI - [Clinical studies on hematological malignancies accompanied by hypercalcemia]. PMID- 2881006 TI - [Detection of anti-ATLA (adult T-cell leukemia-cell associated antigen) antibodies using both indirect immunofluorescence method and particle agglutination test]. PMID- 2881007 TI - [Successful operation of gastric and lung cancer in adult T-cell leukemia]. PMID- 2881008 TI - [Structure of the human T-lymphotropic virus and biological function- transformation and cytopathic effect]. PMID- 2881010 TI - [Abnormal lymphocytes in HTLV infections and its clinical significance]. PMID- 2881009 TI - [Relation between characteristics and physiopathology of adult T-cell leukemia cells]. PMID- 2881011 TI - [Mechanism of tumorigenesis by the HTLV-I virus]. PMID- 2881012 TI - [Clinical statistics of adult T-cell leukemia and HTLV carriers]. PMID- 2881013 TI - [Cellular immunity in adult T-cell leukemia]. PMID- 2881014 TI - [Problems of blood transfusion with positive anti-ATLA antibodies]. PMID- 2881015 TI - [Mother-to-child transmission of HTLV-I]. PMID- 2881016 TI - [Development of a vaccine for adult T-cell leukemia]. PMID- 2881017 TI - Important role of adrenergic function in the development of analgesic tolerance to morphine in mice. AB - The involvement of a catecholaminergic mechanism in the production of morphine analgesia and the development of tolerance to the effect has been suggested. Here, using various adrenergic blockers, the role of adrenergic function in the mechanism was examined. Phentolamine (alpha 1 + alpha 2-blocker, 10, 1 and 0.5 mg/kg), prazosin (alpha 1-blocker, 0.1 and 0.02 mg/kg), propranolol (beta 1 + beta 2-blocker, 10, 1 and 0.5 mg/kg), metoprolol (beta 1-blocker, 10 and 1 mg/kg) did not affect morphine analgesia, but dose-dependently suppressed the development of tolerance to morphine. Yohimbine (alpha 2-blocker, 5 and 1 mg/kg) dose-dependently antagonized morphine analgesia in naive animals and delayed the development of tolerance to morphine. Pindolol (beta 1 + beta 2-blocker but is devoid of membrane stabilizing activity) suppressed the development of tolerance to morphine analgesia; however, d-propranolol, which possesses membrane stabilizing activity but lacks beta-blocking activity, could not prevent the development of tolerance. Thus, the suppressive effect of propranolol on the development of tolerance is not due to membrane stabilizing properties. Not only the non-selective adrenergic blockers, phentolamine and propranolol, but also the selective blockers of each receptor subtype, prazosin and metoprolol, suppressed the development of tolerance. This fact may suggest the importance of the equilibrated state of adrenergic functions in the mechanism for the development of tolerance to morphine. PMID- 2881018 TI - Contractile effects of jellyfish toxin extracted from Carybdea rastonii on isolated rabbit aorta. AB - Effects of the toxic component of jellyfish (Carybdea rastonii) (pCrTX) on the smooth muscle tension of isolated rabbit thoracic aorta were examined. pCrTX, at concentrations higher than 10(-7) g/ml, caused slowly developing tension that reached its maximum after about 1 hr. This contraction was partially inhibited by pretreatment of the tissue with phentolamine (5 X 10(-6) M) or indomethacin (10( 5) M). The contraction induced by pCrTX was partially inhibited by nicardipine (10(-7) M) and markedly augmented by Bay k8644 (10(-6) M). In low-Na+ solution, the rate of rise of the pCrTX-induced contraction was significantly reduced. Removal of external Ca2+ inhibited the pCrTX-induced contraction by about 30%, while chlorpromazine, trifluoperazine, prenylamine and papaverine (10(-4) M) completely inhibited the contraction. pCrTX itself did not cause any contraction in saponin-skinned smooth muscle and had no effect on the Ca2+-induced contractile tension. It has been reported that pCrTX-induced contraction is attributable to the release of endogenous catecholamines and also to the increase in Ca2+ influx in smooth muscle (Azuma et al., 1986). The present results confirmed the previous suggestion and further suggested that a portion of the contraction is due to release of prostaglandin(s) and also to the direct effect on smooth muscle which is not dependent on Ca2+ influx. PMID- 2881019 TI - [Changes in serum proteins including antibodies and chemical mediators during the dual asthmatic response]. PMID- 2881020 TI - Getah virus isolations from mosquitoes in an enzootic area in Japan. PMID- 2881021 TI - Getah virus isolations from mosquitoes collected at two horse habitations in the western areas of Japan. PMID- 2881022 TI - Use of emetic, adsorbent, and cathartic agents in acute drug overdose. PMID- 2881024 TI - [Experience with the treatment of infectious-toxic shock in patients with hemorrhagic fever with the renal syndrome]. PMID- 2881025 TI - [Concentration of somatotropic and thyrotropic hormones in the plasma of patients with hemorrhagic fever with the renal syndrome and persons who have sustained such an illness]. PMID- 2881026 TI - The integrated effect of adrenergic blockade on glucose, fatty acid, and glycerol kinetics: responses in the basal state and during hormonal control with somatostatin-hormonal infusion. AB - We have used primed constant infusions of [1-13C]palmitic acid, [2-3H]glycerol, and [U-14C]glucose to evaluate the response of glucose and fat kinetics to alpha or beta adrenergic blockade in conscious dogs. The response of each blocking agent was evaluated both with and without control of the glucoregulatory hormones. When hormones were controlled, somatostatin and metyrapone were infused to block hormonal secretion, and insulin, glucagon, growth hormone, and cortisol were replaced at basal physiological rates. alpha blockade (beta stimulation) did not influence glucose production or oxidation, but it did decrease glucose clearance when hormones were controlled. Clearance did not decrease during blockade when hormones were not controlled, presumably because of the resulting increase in the plasma insulin concentration. Glucose production, plasma glucose concentration, and glucose oxidation all increased with beta blockade (alpha stimulation). alpha blockade (beta stimulation) resulted in an increase in lipolysis, whereas beta blockade (alpha stimulation) resulted in a decrease in lipolysis. In neither case, however, did FFA oxidation change. We conclude that (a) the predominant effect of unopposed stimulation is the stimulation of lipolysis, whereas unopposed alpha stimulation inhibits lipolysis. Direct effects of either alpha or beta stimulation on glucose kinetics are less dramatic, but both alpha and beta stimulation decrease glucose clearance. PMID- 2881027 TI - [Pharmacology of the venous system]. AB - The presence of alpha 1-receptors has been demonstrated in numerous venous fragments for various animal models. On the other hand, the presence of alpha 2 receptors in the saphenous of the dog is a matter of debate. Beta 2-receptors are activated by isoproterenol, noradrenaline and adrenaline in precontracted veins (part of the facial vein of the rabbit may be an exception). Preferential blocking by atenolol of beta 1-receptors in the jugular veins of the rat suggests that these receptors may mediate vasodilation. The saphenous veins of the dog provide the only example where specific dopaminergic receptors have been noted following partial antagonism with haloperidol. The vasoconstrictive action of acetylcholine has been seen in venous segments of numerous species and indicates the presence of muscarinic receptors. The existence of angiotensin receptors can be postulated despite the weak and inconstant in vitro and in vivo (the dorsal cerebral sinus in the dog excepted) reactions observed and the use of a non specific antagonist. The same is true for bradykinin and vasopressin. The marked vasoconstrictive action of serotonin on all veins studied is evidence for the presence of receptors. The nature of the antagonists is subject to some divergence of opinion. Nevertheless, D tryptamine muscular receptors (or 5 HT2) can be identified due to the lack of morphine-mediated response and the efficacy of methysergide. The presence of a third type of serotoninergic receptor has only been reported once, following observations of vasodilation in the sheep. H1 receptors are involved in histamine-mediated vasoconstriction. The presence of H2 receptors which mediate vasodilation in precontracted veins remains hypothetical. Prostaglandins exhibit different efficacies in producing contraction in isolated veins; PGF2 alpha is more efficacious than PGE1 and PGE2. Prostacyclin induces contraction of human saphenous veins in a dose-dependent manner. PGE2 and particularly PGE1 can induce relaxation in precontracted veins, as is also true for prostacyclin. Receptors for these prostaglandins must exist at the post junctional level. P2-receptors mediate transmission of the vasoconstrictive action of various purine derivatives. PMID- 2881023 TI - Prophylaxis of first variceal hemorrhage in patients with liver cirrhosis. AB - Prophylaxis of bleeding from esophageal varices is a very tempting concept at first glance, especially under the assumption of a high mortality associated with first variceal hemorrhage. Up to now four different measures have been tried for prophylaxis: portacaval shunt operation, devascularization procedures, sclerotherapy, and drugs. With the exception of portacaval shunts, ongoing controlled trials show a weak trend toward reduction of variceal bleeding and prolongation of survival in selected patients with compensated cirrhosis and large varices. However, prophylaxis of first variceal bleeding must still be regarded as experimental and should be restricted to controlled clinical studies. PMID- 2881028 TI - [Current data on insulin secretion and its regulation]. AB - Glucose is the main stimulator and physiological regulator of insulin secretion. The great sensitivity of the B cell to glucose variations between 1 g/l (5.5 mM) and 3 g/l (16.6 mM) and its rapid response ensure the constant adaptation of its secretion to plasma glucose level. The cellular mechanisms involved in insulin response can be schematically represented in three stages: The first stage is the recognition of the insulinotropic agent. In the case of glucose, this involves its metabolism. The second one is the coupling of the recognition process to activation of the effector system and implies a series of intracellular signals. Coupling factors include metabolites and cofactors, ions, cyclic AMP, polyphosphoinositides. The result of all these cellular events is the increase in cytosolic Ca2+ and the activation of protein-kinases: Ca2+-calmodulin-, cAMP- and Ca2+-phospholipid-dependent protein kinases. The last stage corresponds to a mechanical one, involving granule migration and extrusion. The polymerization of microtubules associated with contraction of microfilaments would cause granule movement. Ca2+-calmodulin-dependent protein kinases would play a major role. While glucose is the main stimulator of insulin secretion, numerous factors can influence it. The regulation of this secretion is essentially under the control of three classes of elements: nutrients, hormones and neurotransmitters. As to stimulation of insulin secretion by nutrients, it seems to be secondary to an increase in intracellular metabolism. However it must be underlined that the insulin secretory effect of most nutrients requires the presence of glucose which is consequently a permissive factor. A number of gastrointestinal and pancreatic hormones stimulate, in presence of glucose, insulin secretion and play an essential role during food intake, which results in a better fitting of insulin secretion to energy supply. The term "incretin" designates a hormonal transmitter between the gastrointestinal tract and the B cell; the "incretin" factors are included in what is termed enteroinsular axis. Of the gastrointestinal hormones, GIP (gastric inhibitory polypeptide) appears to play the most important physiological role in potentiating the insulin secretory effect of glucose. Pancreatic glucagon potentiates the effect of glucose too; it is difficult to distinguish between its endocrine and paracrine role. The pancreatic B cell is under neural regulation. The cholinergic system stimulates insulin secretion and the B cell is fitted with receptors of muscarinic type.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2881029 TI - Effects of an extract of khat (Catha edulis) on the toad heart. AB - The effects of acute and chronic administration of an extract of Catha edulis on the heart of the toad were investigated. ECG and ventricular action potential were recorded simultaneously from the surface of the heart of spinal pithed toads before and after administration of different doses of khat extract. Acute treatment resulted in a dose-dependent chronotropic effect and an increase in the amplitude of ventricular action potential. Chronic treatment on the other hand resulted in a negative chronotropic effect and a reduction in the amplitude of ventricular action potential. The observed responses are explained on the basis of the catecholamine releasing effect of components of khat extract. PMID- 2881030 TI - Alteration of dopamine receptors in the caudate nucleus and the putamen in schizophrenic brain. AB - Neuroleptic binding to human caudate and putamen was investigated in seven patients with schizophrenia and compared to matched normal controls. [3H] spiperone was used as a ligand for the binding studies and previous drug treatment was recorded. There was a statistically significant increase in maximal specific binding and in dissociation constants for [3H]-spiperone in the brains of schizophrenics in both brain regions studied. Long term as well as recent neuroleptic treatment both appeared to be associated with increases of Bmax and Kd of [3H]-spiperone. PMID- 2881031 TI - [Lymphotropic retroviruses of human T lymphocytes: T lymphocyte leukemia-lymphoma of the adult and acquired immunodeficiency syndrome]. PMID- 2881032 TI - Analgesic drug therapy in cancer pain: principles and practice. AB - Drug therapy represents the mainstay of treatment for patients with cancer pain. Non-narcotic, narcotic, and adjuvant analgesics are the commonly used agents. The choice of a specific analgesic drug regimen is dependent on the type of pain and its severity, and the drug must be titrated to the individual needs of the patient. PMID- 2881033 TI - Continuous intravenous infusion of opioid drugs. AB - Continuous intravenous infusion of opioid drugs is a widely accepted alternative approach to the management of cancer pain. This review critically evaluates the safety and efficacy of the technique and proffers guidelines for management based on the available literature and clinical experience. PMID- 2881034 TI - Role of epidural and intrathecal narcotics and peptides in the management of cancer pain. AB - The spinal administration of opioids may provide analgesia of long duration to patients with bilateral or midline lower abdominal or pelvic cancer pain. However, cross-tolerance to orally and parenterally administered narcotics and the rapid development of tolerance to spinal narcotics have limited their usefulness. Opioids have extensive distribution in the CSF and plasma when administered into the epidural or intrathecal space, and delivery of drug to brain stem sites may account for many of the toxic and therapeutic effects of spinal opioids. Further clinical and pharmacokinetic studies are required to provide the information regarding: the optimal opioids for use as spinal analgesics; equieffective dose ratios of spinal opioids in comparison to parenteral or oral opioids; strategies useful to forestall the development of tolerance of spinally administered opioids; the analgesic efficacy of this therapy in opioid-tolerant patients; and the role of spinally administered nonopioid analgesics in the management of cancer pain in the tolerant patient. These questions will need resolution before this therapy can be recommended for routine use in the management of cancer pain. PMID- 2881035 TI - Antitumor and antinociceptive approaches to control cancer pain. AB - Patients with cancer pain often present with specific clinical syndromes that allow specific anti-tumor approaches. If these approaches are not feasible, neurosurgical procedures for pain relief should be considered. The major advantage of neurosurgical procedures is freedom from the excessive side effects of narcotic therapy. The most durable pain procedure is cordotomy, while intraspinal narcotics offer a rational treatment alternative in selected patients. Spinal and plexopathy syndromes that are amenable to more specific anti tumor therapy should be looked for, since newer surgical approaches offer the prospect of both pain relief and tumor control. PMID- 2881036 TI - [2 international multicenter studies. Early treatment with beta blockaders in acute chest pain reduces the risk of definitive development of myocardial infarction]. PMID- 2881037 TI - Anaesthetic-induced increase in ionised calcium in blood mononuclear cells from malignant hyperthermia patients. AB - The cytoplasmic concentration of ionised calcium, [Ca2+]i, is believed to be altered by agents that induce a malignant hyperthermia (MH) crisis in susceptible individuals. MH patients were identified by the halothane and halothane/caffeine contracture tests done in isolated muscle biopsy specimens. [Ca2+]i was measured in isolated peripheral blood mononuclear cells from MH patients and controls by means of the fluorescent calcium ion indicator quin2. In the absence of halothane there was no significant difference in [Ca2+]i in cells from normal and MH patients. Addition of halothane (4 microliter/ml) significantly increased [Ca2+]i in cells from MH patients but not in controls. The halothane-induced increase in [Ca2+]i required extracellular calcium ions. This is the first evidence of the mechanism of action of halothane in cells of MH patients; the differential effect of halothane on [Ca2+]i might constitute the basis for a non-invasive screening test for MH. PMID- 2881038 TI - Vitamin E supplementation reduces frequency of periventricular haemorrhage in very preterm babies. AB - 231 babies, born at less than or equal to 32 weeks' gestation were enrolled in a randomised, controlled trial to assess the efficacy of vitamin E (dl-alpha tocopherol acetate) in the prevention of periventricular haemorrhage. Daily supplementation with 20 mg/kg vitamin E intramuscularly during the first 3 days of life was associated with a rise in plasma vitamin E concentration and a reduction in hydrogen peroxide haemolysis of red blood cells in vitro. Among babies without haemorrhage on entry to the trial (n = 210), supplemented babies had a lower frequency of intraventricular haemorrhage than controls (8.8% v 34.3%; p less than 0.005) and a lower combined frequency of intraventricular and parenchymal haemorrhage (10.8% v 40.7%; p less than 0.0001) on the final ultrasound brain scan. This protective effect was observed in both inborn and referred babies but was stronger in the former. Supplementation had no effect on mortality, but among survivors fewer supplemented babies than controls had intraventricular or parenchymal haemorrhage (10.7% v 32.6%; p less than 0.001). Possibly, vitamin E scavenges free radicals generated during ischaemic injury of the subependymal region and thereby limits tissue damage and the extent of periventricular haemorrhage on reperfusion. PMID- 2881039 TI - Herpes-virus immunity and acute graft-versus-host disease. AB - The influence of pretransplant herpes-virus antibodies in 126 marrow-graft recipients and their HLA-identical (A, B, C, DR) sibling donors on the incidence of grades II-IV acute graft-versus-host disease (GVHD) was studied in relation to previously reported risk factors for GVHD. Logistic regression procedures were used to control for confounding factors. Increasing donor age (odds ratio 3.7 per decade; p = 0.02) and donor seronegativity for Epstein-Barr virus (EBV; odds ratio 10.1; p = 0.005) were associated with a high incidence of GVHD. Total rather than selective gastrointestinal decontamination (odds ratio 0.1; p = 0.004), donor seronegativity for herpes simplex virus (HSV; odds ratio 0.1; p = 0.003), and recipient EBV-seronegativity (odds ratio 0.05; p = 0.002) were associated with a low incidence of GVHD. Pretransplant EBV and HSV serology may thus contribute substantially to the estimation of the risk for GVHD. PMID- 2881040 TI - Haemolytic transfusion reactions due to HLA antibodies. A prospective study combining red-cell serology with investigations of chromium-51-labelled red-cell kinetics. AB - In a prospective study to see whether HLA sensitisation is associated with increased red-blood-cell (RBC) destruction after HLA-incompatible transfusion, chromium-51-labelled RBC survival and site of sequestration were monitored in nine patients in whom HLA antibodies had developed after RBC transfusions. The donors selected were compatible in ABO and RBC-specific antigen systems but mismatched for the HLA antigen in question. Haemolytic transfusion reactions occurred in all four patients who received HLA-B7-incompatible RBC. A direct radioimmune anti-IgG test became positive, Cr51-RBC survival was very short (22.3, 36.9, 41.4, and 44.0 days), and excess sequestration in the spleen was measured. There was a rise in serum lactic dehydrogenase and a fall in haptoglobin. HLA-B7 antibody was detected in the eluate prepared from RBC collected after transfusion. A similar reaction was found in only one further patient, caused by an HLA-A2 incompatibility. No indications of immune-mediated RBC sequestration were discernible after transfusion of HLA-B7-compatible RBC in one of the patients who had shown a reaction with HLA-B7-incompatible blood, nor in any of the other patients who received HLA-B7-compatible RBC. The haemolytic transfusion reactions could not be anticipated by conventional crossmatch procedures, nor by the measurement of the Cr51-RBC survival 1 h after transfusion. PMID- 2881042 TI - Progressive systemic sclerosis: autoimmune arteriopathy. AB - In a case of progressive systemic sclerosis (PSS), widespread deposition of IgM was found in the media and internal elastic lamina of small muscular arteries. IgA and C3 were also found in some vessels. Antibody eluted from the kidney bound to smooth muscle and elastica of small arteries. These findings suggest that PSS is a vasculopathy which is mediated by complement-fixing antibodies. PMID- 2881043 TI - Food irradiation. PMID- 2881041 TI - Serological response to the hepatitis delta virus in hepatitis D. AB - Sera from 74 hepatitis B surface antigen-positive individuals, who presented with acute hepatitis delta virus (HDV) infection which ran a self-limited course in 58 and progressed to chronicity in 16, were tested over time for HDV markers. In self-limited disease the serum pattern varied from early HD-antigenaemia followed by IgM and IgG anti-HD seroconversion, to the appearance of IgM and IgG anti-HD without antigenaemia, or the isolated expression of either the IgM or the IgG antibody. The typical case of IgM anti-HD was transient and appeared with a mean delay of 10-15 days from admission in the different serological subgroups. The IgG antibody usually developed several weeks later during convalescence. In contrast, patients with disease destined to become chronic had a brisk IgM antibody response and IgG anti-HD was detectable with a mean delay of 15 days; generally, the IgM and the IgG antibody persisted over the follow-up time. IgM antibody to HDV is often the only serological test positive in the clinical stage of hepatitis D and repeated testing for this marker is necessary to diagnose acute HDV co-infection. The serological follow-up provides important prognostic information: waning of IgM confirms resolution of HDV infection, persistence predicts chronicity. PMID- 2881044 TI - Colposcopy today. PMID- 2881046 TI - The known and the unknown about dengue fever. PMID- 2881045 TI - Report with confidence. PMID- 2881047 TI - A mockery of health promotion. PMID- 2881048 TI - Congenital hypothyroidism: increased risk of neonatal morbidity results in delayed treatment. AB - In a population-based screen of 617,913 infants, primary congenital hypothyroidism (CH) was confirmed in 100 children. 32 of the 100 infants with CH had an additional defect or complication. In the group with CH the rates of congenital heart disease, non-cardiac malformations, respiratory distress syndrome, and death were higher than in the general population of the same age. Black infants were less likely than whites to have CH, but were at twice the risk of additional impairment. Infants with CH who had an additional complication were screened (12.7 vs 4.8 days) and treated (32.4 vs 19.7 days) significantly later than those infants with isolated CH. Congenital malformations and neonatal complications should not be reasons for deferring screening for CH. PMID- 2881051 TI - Human genetics: fragile sites still a mystery. PMID- 2881050 TI - Confidence intervals. PMID- 2881052 TI - Dementia and Parkinson's disease associated with diffuse cortical Lewy bodies. PMID- 2881049 TI - Evaluation of a clinical case-definition of acquired immunodeficiency syndrome in Africa. AB - A provisional clinical case-definition for acquired immunodeficiency syndrome (AIDS) developed by the World Health Organisation (WHO) for use in Africa was tested on 174 inpatients at Mama Yemo Hospital, Kinshasa, Zaire. In this hospital population with a 34% infection rate of human immunodeficiency virus (HIV), the clinical case-definition had a specificity of 90%, a sensitivity of 59%, and a predictive value of 74% for HIV seropositivity. These results support the use of the WHO clinical definition for AIDS in Africa. However, since HIV prevalence and disease expression vary, similar evaluations should be carried out in different regions. PMID- 2881053 TI - Pseudorabies in man. PMID- 2881054 TI - Intravenous streptokinase given within 0-4 hours of onset of myocardial infarction reduced mortality in ISIS-2. PMID- 2881055 TI - Serum cholesterol, blood pressure, and mortality. PMID- 2881056 TI - Statistical analysis of lipid research clinics program. PMID- 2881057 TI - Focus of Rift Valley fever virus transmission in southern Mauritania. PMID- 2881058 TI - Viability of autologous bone marrow. PMID- 2881059 TI - Amoebae research. PMID- 2881060 TI - Antibiotic levels in bronchopulmonary tissue. PMID- 2881061 TI - Detection of skin nodules in onchocerciasis by ultrasound scans. PMID- 2881062 TI - Cerebral dominance, handedness, and epilepsy. PMID- 2881063 TI - Diabetic complications in end-stage diabetic nephropathy. PMID- 2881064 TI - Plasma exchange for cerebral lupus erythematosus. PMID- 2881065 TI - Histiocytosis in baby with delayed cord separation. PMID- 2881067 TI - Risk factors in oesophageal cancer. PMID- 2881068 TI - Vitamin E and Parkinson's disease. PMID- 2881066 TI - Antioestrogen therapy of pure mesenchymal tumour. PMID- 2881070 TI - Differential diagnosis in child sexual abuse. PMID- 2881069 TI - Treatment of drug addiction. PMID- 2881071 TI - Community campaign for iron deficiency. PMID- 2881072 TI - Early diagnosis in hereditary retinoblastoma by detection of molecular deletions at gene locus. PMID- 2881073 TI - Post-mortem recognition of inherited metabolic disorders from specific acylcarnitines in tissue in cases of sudden infant death. PMID- 2881074 TI - Screening for malignant phenylketonuria. PMID- 2881075 TI - Echocardiography in systemic sarcoidosis. PMID- 2881076 TI - Monoclonal marker that predicts early recurrence of breast cancer. PMID- 2881077 TI - Adrenal suppression after long-term exposure to occupational corticosteroids followed by rapid recovery. PMID- 2881078 TI - Back pain and testicular germ cell tumours. PMID- 2881080 TI - Mesna and total body irradiation. PMID- 2881079 TI - Acute renal failure after topical application of carbon tetrachloride. PMID- 2881081 TI - Skin reactions to long-term transdermal clonidine. PMID- 2881082 TI - Risk of stroke in non-rheumatic atrial fibrillation. AB - Estimates of the risk of stroke for men with non-rheumatic atrial fibrillation were obtained from two large cohort studies--the Whitehall Study of London Civil Servants and the British Regional Heart Study. The first cohort provided an estimated relative risk of stroke of 6.9 compared with controls. This increased risk confirms that of the other prospective estimate, 5.6, found in the Framingham study. In the second cohort only one of the men at risk had a stroke, and the risk estimate did not differ significantly from unity. The absolute rates of stroke in both cohorts were lower than those reported in the Framingham study, implying a lesser potential benefit from preventive measures. These lower rates should be considered in the planning of trials. The risk of stroke was significantly associated with raised systolic or diastolic blood pressure but not with age or coronary heart disease. PMID- 2881083 TI - Yersinia infection and acute abdominal pain. AB - In 194 patients presenting with acute abdominal pain from whom sequential serum samples were taken, the frequency of yersiniosis, established serologically, was significantly higher (23%) than in 320 control subjects (2%). Yersiniosis occurred in 31% of patients with acute appendicitis. Acute-phase serum samples only, obtained in a further 307 patients, yielded a falsely low frequency of yersiniosis (4%). Y pseudotuberculosis was five times more common than Y enterocolitica, and Y pseudotuberculosis type IV was the most common serotype, accounting for 43% of Yersinia infections. Yersinia may play a more important part in the aetiology of acute abdominal pain, and particularly acute appendicitis, than has been previously appreciated. Antibody titres to both Y enterocolitica and Y pseudotuberculosis frequently rise late in infections causing abdominal pain. Consequently analysis of acute-phase serum samples alone leads to underdiagnosis of yersiniosis. PMID- 2881084 TI - Increased platelet Na+-H+ exchange rates in essential hypertension: application of a novel test. AB - Enhanced sodium-proton exchange may play a role in the pathogenesis of hypertension. Na+-H+ exchange was measured indirectly in platelets as the rate of amiloride-sensitive and sodium-dependent volume gain of cells suspended in sodium propionate; the cytoplasmic acidification induced by the permeant propionic acid activated the exchanger and the volume changes coupled to Na+ uptake were measured by cell sizing with a Coulter counter and 'Channelyzer'. The test was rapid, simple, and reproducible. 20 normotensives; 8 normotensives with a family history of hypertension; 15 patients with essential hypertension receiving medication; and 7 hypertensives who had not received any antihypertensive drugs were studied. The exchange rate constants of these groups were (mean [SE] in s-1 X 10(-3)) 13.1 (0.6); 15.5 (0.7); 18.4 (0.9); and 25.6 (2.8), respectively. The differences between hypertensives and normotensives were significant. Measurement of sodium-proton exchange in platelets may help to clarify the pathogenesis of hypertension. PMID- 2881085 TI - Diagnosis of cervical neoplasia by the estimation of octadeca-9,11-dienoic acid. AB - Exfoliated cells from the precancerous cervix have an increased concentration of octadeca-9,11-dienoic acid, a diene-conjugated isomer of linoleic acid. A high performance liquid chromatographic method which measures both has been automated. It may form the basis of a sensitive diagnostic test. PMID- 2881086 TI - Breast cancer screening. PMID- 2881087 TI - Should all patients with retinoblastoma be screened for chromosome deletions? PMID- 2881089 TI - Somatosensory potentials and cervical cord disease. PMID- 2881088 TI - Management of behaviour problems in children with mental handicap. PMID- 2881090 TI - The controlled clinical trial: consensus? PMID- 2881091 TI - Caesarean section for dystocia: a comparison of practices in two countries. AB - Retrospective data collected from the medical records of 1040 low-risk nulliparous obstetric patients presenting for delivery in a general community hospital in Ireland and a comparable one in the United States showed a significantly higher rate of caesarean section for dystocia or abnormal labour in the American hospital--a discrepancy which was not easily explained by differences in patient characteristics (eg, maternal age, known risk factors, birthweight). Acceleration of labour with oxytocin was significantly more common in the Irish group, and average duration of labour was shorter. No advantage to the infant, as measured by the Apgar score, resulted from the greater use of caesarean section for dystocia. PMID- 2881092 TI - Experience with an automatic implantable cardioverter defibrillator. PMID- 2881093 TI - Crisis at Christmas 1986. AB - Of 100 men and women interviewed at Crisis at Christmas, 34 were actively psychotic, and 12 of these had had no contact with psychiatric services. Of those also answering as to whether or not they had been in prison, 25 (81%) replied in the affirmative, including 1 who had been in Broadmoor for attempted murder. In the combined group of 46 who either had had previous psychiatric admissions or were actively psychotic, 32 (78%) admitted to having been to prison (2 declined to answer), which was significantly in excess of the figure (42%) for those with no serious psychopathology and no previous psychiatric history. About a third of those interviewed were not receiving their benefit entitlement, the proportions being similar for those with and without a history of psychiatric illness. These results show a deterioration since last year's survey. PMID- 2881094 TI - Cancer near nuclear installations. PMID- 2881095 TI - Multiresistant invasive Escherichia coli infection in south London. PMID- 2881096 TI - Lyme borreliosis in Belgium. PMID- 2881097 TI - Diphtheria revaccination of adults. PMID- 2881098 TI - Acetazolamide interferes with theophylline assay. PMID- 2881099 TI - Detection of methicillin-resistant Staphylococcus aureus. PMID- 2881100 TI - Morbidity of hyperparathyroidism. PMID- 2881101 TI - N-myc oncogene amplification and catecholamine metabolism in children with neuroblastoma. PMID- 2881103 TI - Metabolic bone disease of prematurity. PMID- 2881102 TI - Rabbit (to replace human) brain material in anticoagulant control. PMID- 2881104 TI - Media for isolating Shigella. PMID- 2881105 TI - Recombination within DXS52 (ST14) locus in family with haemophilia A. PMID- 2881106 TI - Birth sex ratios and prostatic cancer in butchers. PMID- 2881107 TI - Sphygmomanometer bladder length and measurement of blood pressure in children. PMID- 2881108 TI - Doppler flow velocity in anterior cerebral artery for prediction of outcome after perinatal asphyxia. PMID- 2881109 TI - Increased serum ferritin levels in adult Still's disease. PMID- 2881110 TI - Obstetric emergency hysterectomy? PMID- 2881111 TI - Prognosis of women with human papillomavirus DNA in normal tissue distal to invasive cervical and vulval cancer. PMID- 2881112 TI - Advertising in antenatal clinics. PMID- 2881113 TI - Training for blood transfusion. PMID- 2881115 TI - HIV antigen detection in routine blood donor screening. PMID- 2881114 TI - HIV antigen testing. PMID- 2881116 TI - HIV antigenaemia in acute HIV infection. PMID- 2881117 TI - Detection of HIV antigens in eluates from whole blood collected on filterpaper. PMID- 2881118 TI - Condoms and AIDS prevention. PMID- 2881119 TI - Psychological disturbances in idiopathic oedema. PMID- 2881120 TI - Perforation of superior vena cava by indwelling central venous catheters. PMID- 2881121 TI - Overwhelming pneumococcal sepsis post-splenectomy. PMID- 2881122 TI - Radiosensitization after busulphan. PMID- 2881123 TI - Effects of dexamethasone in brain tumour patients. PMID- 2881124 TI - Chlorproguanil chemoprophylaxis for falciparum malaria in Kenya. PMID- 2881125 TI - In-vitro chloroquine and mefloquine-resistant Plasmodium falciparum in Nigeria. PMID- 2881126 TI - Acute hypoadrenalism and hepatotoxicity after treatment with ketoconazole. PMID- 2881127 TI - Spinal level analgesia after morphine overdose? PMID- 2881128 TI - An action by putative father and unborn fetus to prevent termination. PMID- 2881129 TI - Benefits and potential harm of lowering high blood pressure. AB - To investigate whether the lower the blood pressure (BP) the better the prognosis for the patient with moderate-to-severe hypertension, an assessment was made of 902 patients who received the beta 1-selective beta-blocker atenolol (median dose 100 mg a day), either alone or with other antihypertensive agents, for up to 10 years (mean 6.1). 91 died, 40 from myocardial infarction, 21 from stroke, and 30 from other causes. Initial BP was a poor predictor of mortality from myocardial infarction, whereas treated systolic blood pressure (SBP) was a strong predictor. There was a J-shaped relation, confined to those with evidence of ischaemic heart disease, between frequency of death from myocardial infarction and treated DBP (phase V); the frequency was lowest at treated DBP of 85-90 mm Hg and rose with treated DBP on either side of this range. PMID- 2881130 TI - Cyclosporin treatment with conversion after three months versus conventional immunosuppression in renal allograft recipients. AB - In a prospective randomised trial, 72 recipients of cadaver renal allografts received cyclosporin for 3 months followed by azathioprine and prednisone (cyclosporin group), and 71 received azathioprine and prednisone from the day of transplantation (conventional group). Graft survival was better in the cyclosporin group at 3 months and 1 year (93% and 80%) than in the conventional group (83% and 70%). This was not a significant difference. The incidence of acute rejection episodes in the first 3 months was significantly lower in the cyclosporin group (35% versus 77%, p less than 0.00001), as was the number of grafts lost because of immunological failure (1 versus 10, p less than 0.02). After conversion, renal function improved. Only 5 patients had acute rejection after conversion. These episodes were easily reversible in all cases and did not lead to graft loss. The numbers of grafts lost after conversion were similar in the two groups. Conversion of cyclosporin to azathioprine 3 months after renal transplantation is a safe procedure that obviates the long-term toxic effects of cyclosporin. PMID- 2881131 TI - Cyclosporin conversion versus conventional immunosuppression: long-term follow-up and histological evaluation. AB - 129 patients who received a cadaver renal transplant entered a randomised prospective trial of cyclosporin for 3 months with conversion to azathioprine and prednisolone compared with conventional therapy of azathioprine and prednisolone. In the 64 patients who received cyclosporin, actuarial patient survival was 92%, and actuarial graft survival was 72% and 67% at 1 and 4 years after transplantation. Graft survival was significantly better (p less than 0.03) than in the 65 patients who received conventional therapy, in whom actuarial patient survival was 94%, and actuarial graft survival was 59% and 47% at 1 and 4 years. Renal function and other side-effects improved quickly after conversion with the better renal function maintained throughout follow-up. Renal biopsies at 90 days and 1 year in all patients did not show consistent improvement after conversion from cyclosporin in the histological features that might be attributable to cyclosporin toxicity. After conversion, 32% of the patients had acute rejection, generally within 30 days. 1 graft was lost to early acute rejection after conversion and another was lost 3 months later from acute-on-chronic rejection. A total of 8 grafts were lost to chronic rejection in the cyclosporin-treated group and 6 in the conventional group. The improvement in renal function obtained with this protocol of short-term cyclosporin with conversion to azathioprine and prednisolone has to be balanced against the risk of acute rejection and even loss of the graft after conversion. PMID- 2881132 TI - Antibiotic elimination of group-B streptococci in urine in prevention of preterm labour. AB - The presence of group-B streptococci in the urine of pregnant women seems to be associated with preterm labour. Urine samples from 4122 women at 27-31 weeks' gestation were examined for bacteria. Group-B streptococci were found in the urine of 69 women. In a double-blind, controlled study these patients were given either penicillin (10(6) IU three times daily for 6 days; 37 patients) or placebo (32 patients). The rates of primary rupture of the membranes (11% v 53%; p less than 0.001) and preterm labour (5.4% v 38%; p less than 0.002) were significantly lower in the penicillin group than in the placebo group. These results suggest that treatment and follow-up to prevent recolonisation in pregnant women with group-B streptococci in the urine may reduce the frequency of preterm labour in these patients. PMID- 2881134 TI - Serum reactivity to human T-cell leukaemia/lymphoma virus type I proteins in patients with large granular lymphocytic leukaemia. AB - To investigate the possibility that the recently recognised syndrome, leukaemia of large granular lymphocytes, could be associated with human T-cell leukaemia/lymphoma virus type I (HTLV-I), sera from 12 patients with this type of leukaemia were tested by the use of western-blot techniques for IgG antibodies to proteins related to human T-cell leukaemia/lymphoma virus type I (HTLV-I). Sera from 6 patients, including 2 patients with rheumatoid arthritis, reacted with p19 or p24 retroviral proteins or both. In contrast, no sample from 32 patients with uncomplicated rheumatoid arthritis, 27 with Felty's syndrome, 11 with other connective tissue disorders, or 21 normal individuals reacted with HTLV-I. The results suggest that leukaemia of large granular lymphocytes may be associated with a retrovirus related to HTLV-I. PMID- 2881133 TI - Identification of placental protein 14 as an immunosuppressive factor in human reproduction. AB - Extracts of human decidual tissue obtained in the first trimester of pregnancy showed potent suppressive activity in mixed lymphocyte cultures. These extracts contained substantial amounts of the decidual protein PP14. Purified PP14 also exhibited in vitro immunosuppressive activity, and such activity in decidual extract and purified PP14 preparations was removed by treatment with a monoclonal anti-PP14 antibody-based immunoadsorbent. PP14 was present in seminal plasma, which also exhibited immunosuppressive activity that could be reduced, but not removed, by the immunoadsorbent. PP14 may be an important immunomodulator in the human reproductive system. PMID- 2881135 TI - Prevention of coronary heart disease. PMID- 2881136 TI - Geriatric consultation teams. PMID- 2881137 TI - Thallium poisoning in Guyana--a national crisis. PMID- 2881139 TI - Who should treat Hodgkin's disease--and where? PMID- 2881138 TI - The solitary brain tumour. PMID- 2881140 TI - An appraisal of the epidemic rise of coronary heart disease and its decline. AB - Epidemiologists have used mortality statistics to demonstrate a sharp rise in the incidence of coronary heart disease in several countries since the turn of the century and a decline in some countries since the late 1960s. However, increased longevity, changes in coding and diagnostic practices, and familiarity with the clinical and pathological features of the disease make the increase largely spurious. Diagnostic errors in certified causes of death in general, and coronary heart disease in particular, indicate that vital statistics are too unreliable for determining whether there has been an increase and a subsequent decline in the incidence of coronary heart disease. PMID- 2881141 TI - What follows diagnosis by computed tomography of solitary brain tumour? Audit of one year's experience in South East Scotland. AB - The referral rate to neurosurgeons after diagnosis by computed tomography (CT) of solitary brain tumour (SBT) was audited for South East Scotland in 1985. 142 patients had SBT diagnosed by CT, but histological confirmation by biopsy or open operation was sought in only 67. Among these the CT diagnosis of glioma proved to be incorrect in 3 of 44 cases and that of solitary metastasis in 4 of 8 cases. Since CT diagnosis of SBT is not fully reliable, biopsy should be considered in all cases. PMID- 2881142 TI - Acquired immunodeficiency syndrome after travelling in Africa: an epidemiological study in seventeen Caucasian patients. AB - Seventeen Caucasian patients with acquired immunodeficiency syndrome (AIDS) contracted after long stays in Africa are reported. Central Africa was concerned in all cases. Men are particularly exposed to AIDS whatever their occupation. This study suggests that the risk of contracting AIDS in Africa is high; the transmission of the virus was related to sexual contact, particularly with prostitutes, in Africa in most of the cases. It suggests also that Caucasians who travel in Africa spread the virus throughout the world by means of their heterosexual relations. PMID- 2881143 TI - Rationing health care. PMID- 2881145 TI - Caesarean delivery of the second twin. PMID- 2881144 TI - Chronic drainage of fetal pulmonary cyst. PMID- 2881146 TI - Nicotinamide may extend remission phase in insulin-dependent diabetes. PMID- 2881148 TI - Anal appearances and child sex abuse. PMID- 2881147 TI - Safety of and necessity for needle biopsy of liver tumours. PMID- 2881149 TI - Blood pressure monitoring at home for rapid opioid withdrawal with clonidine and naltrexone. PMID- 2881150 TI - Testing cerebrospinal fluid. PMID- 2881151 TI - Olfactory detection and recognition in Alzheimer's disease. PMID- 2881152 TI - Symptomatic hypocalcaemia after treatment with high-dose aminohydroxypropylidene diphosphonate. PMID- 2881153 TI - Effect of ethamsylate on cerebral blood flow. PMID- 2881154 TI - Choline increases acetylcholine release. PMID- 2881155 TI - Dementia in Parkinson's disease in association with diffuse Lewy body disease. PMID- 2881156 TI - Timing of levodopa therapy: evidence from MPTP-treated primates. PMID- 2881157 TI - 24-hour monitoring of oesophageal pH in outpatients. PMID- 2881158 TI - Modern genetics and neuromuscular disorders. PMID- 2881159 TI - Gene location in Tourette syndrome. PMID- 2881160 TI - HLA-DR2 and rapid-eye-movement sleep latency: failure to replicate. PMID- 2881161 TI - In-utero exposure to benzodiazepines. PMID- 2881162 TI - No change in corrected beta 2-microglobulin concentration after cuprophane haemodialysis. PMID- 2881163 TI - Ethanol patch test for low Km aldehyde dehydrogenase deficiency. PMID- 2881164 TI - Diagnosis: the need for demystification. PMID- 2881165 TI - HIV infection among high-risk pregnant women. PMID- 2881166 TI - Delayed and defective anti-HIV IgM response in infants. PMID- 2881167 TI - Blood donor screening by Wellcome anti-HIV kits. PMID- 2881168 TI - Interpretation of isolated HIV anti-p24 reactivity in Western blot analysis. PMID- 2881169 TI - Screening for anti-HIV. PMID- 2881171 TI - Fatty acid pattern and ischaemic heart disease. PMID- 2881170 TI - Dexamethasone and increased intracranial echogenicity. PMID- 2881173 TI - Immunosuppression and type I diabetes. PMID- 2881172 TI - Management of hyperphosphataemia in renal dialysis patients. PMID- 2881175 TI - Adulteration of homoeopathic remedies. PMID- 2881176 TI - Death associated with hyperventilation. PMID- 2881174 TI - Trimethylaminuria (fish-odour syndrome): an inborn error of oxidative metabolism. PMID- 2881177 TI - Oral contraceptives and breast cancer. PMID- 2881178 TI - Prevention of coronary heart disease. PMID- 2881179 TI - Pregnancy following sterilisation: two cases fail. PMID- 2881180 TI - The blood pressure effects of alpha-adrenoceptor antagonists injected in the medullary site of action of clonidine: the nucleus reticularis lateralis. AB - We administered a series of alpha-blocking drugs to the nucleus reticularis lateralis (NRL) of the medulla oblongata, the main site for the hypotensive action of clonidine. These experiments were performed on pentobarbital anaesthetized cats. Drugs were injected through a needle which was stereotaxically inserted. Prazosin (6 nmol) was hypertensive (MBP = +25 +/- 8%), corynanthine had no effect and AR-C239 (7 nmol), another alpha 1-blocker, was hypotensive (MBP = -16 +/- 3.5%). The alpha 2-blockers, yohimbine and idaxozan, were hypotensive. The blood pressure effects of alpha-blocking drugs directly microinjected in the nucleus reticularis lateralis cannot be simply related to their selectivity for a particular subtype of alpha-receptors. PMID- 2881181 TI - Effects of exercise and ethanol on liver mitochondrial function. AB - Rates of ADP stimulated respiration for various substrates were determined in mitochondria isolated from the livers of female Sprague-Dawley rats following 8 weeks of treatment with daily swimming, ethanol consumption, or both. All rats were fed an American Institute of Nutrition (AIN) type liquid diet with the ethanol treated rats receiving 35% of the calories as ethanol. Chronic exposure to ethanol depressed both state 3 respiration with glutamate as a substrate and cytochrome oxidase activity. Respiratory control ratios and P:O ratios, however, were unaffected by the ethanol exposure. Exercise alone had no effect on hepatic mitochondrial function. There were also no significant alterations in oxidative function of hepatic mitochondria from rats which were endurance-trained by swimming while receiving the ethanol diet. This lack of alteration in mitochondrial function was in spite of the fact that these rats consumed an identical amount of ethanol as those which incurred mitochondrial dysfunction. These results indicate that regular exercise has the potential to attenuate the ethanol induced decline in hepatic mitochondria. PMID- 2881182 TI - Effect of the alpha 2-blocker DG-5128 on insulin and somatostatin release from the isolated perfused rat pancreas. AB - 2[2-(4.5-Dihydro-1H-imidazol-2-yl)-1-phenylethyl] pyridine dihydrochloride sesquihydrate (DG-5128) is an alpha 2-specific-adrenergic antagonist. We have studied the effect of DG-5128 on insulin and somatostatin release from the isolated perfused rat pancrease. DG-5128 stimulated somatostatin and insulin release not only at a low glucose concentration but also at a high glucose concentration. These findings suggest that an alpha 2-adrenergic receptor plays an important role in the regulation of insulin and somatostatin secretion. PMID- 2881183 TI - Effect of dual beta-blockade and calcium antagonism on endurance performance. AB - The effect of oral clinically used doses of propranolol, atenolol, nifedipine, propranolol + nifedipine, and atenolol + nifedipine on endurance performance and ventilatory responses to graded treadmill testing was studied in 12 healthy physically active men. Maximal exercise duration was reduced by propranolol (8.5%, P less than 0.001) and its combination with nifedipine (11.1%, P less than 0.001), and to a lesser degree by atenolol (3.2%, 0.05 less than P less than 0.1), nifedipine (2.1%, P less than 0.05), and atenolol + nifedipine (3.9%, P less than 0.01). Exercise duration and heart rate (HR) and ventilatory responses to maximal exercise were equivalent with a beta-blocker and its combination with nifedipine. At submaximal exercise, beta-blockade reduced the HR and oxygen uptake, nifedipine accentuated the HR but did not alter ventilation, and all drugs modified the relative oxygen uptake corresponding to 85% of the maximal HR. Physiologic responses to submaximal exercise during combination therapy were similar to those during beta-blockade alone. This study concludes that, in physically active men, nifedipine induces a small impairment of maximal performance, but does not accentuate the reduction in effort tolerance resulting from beta-blockade. Furthermore, HR and ventilatory responses to exercise during combined beta-blockade and calcium antagonism can be predicted from those during beta-blockade alone. PMID- 2881184 TI - Predicting plantar fasciitis in runners. AB - Ninety-one runners were studied to determine whether specific variables were indicative of runners who had suffered with plantar fasciitis either presently or formerly vs runners who had never suffered with plantar fasciitis. Each runner was asked to complete a running history, was subjected to several anatomical measurements, and was asked to run on a treadmill in both a barefoot and shoe condition at a speed of 3.35 mps (8 min mile pace). Factor coefficients were used in a discriminant function analysis which revealed that, when group membership was predicted, 63% of the runners could be correctly assigned to their group. Considering that 76% of the control group was correctly predicted, it was concluded that the predictor variables were able to correctly predict membership of the control group, but not able to correctly predict the presently or formerly injured sufferers of plantar fasciitis. PMID- 2881185 TI - Detection of metabolites in rabbit brain by 13C NMR spectroscopy following administration of [1-13C]glucose. AB - 1H-decoupled 13C NMR spectra (20.2 MHz) of the living rabbit brain were collected with a surface coil following the intravenous infusion of [1-13C]glucose. Within 15 min of infusion, the alpha and beta anomers of glucose were detected and, shortly thereafter, the carbon atoms at positions C4, C3, and C2 of glutamate and(or) glutamine. After reductions of inspired oxygen from 30 to 5%, lactate C3 was detected. The intensity of the lactate resonance rose progressively during hypoxia and later fell during recovery with oxygen. The 13C fractional isotopic enrichment of arterial blood glucose was measured by 1H NMR providing information on the rate and extent of blood glucose labeling. PMID- 2881186 TI - Comparison of N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase activities for evaluation of microangiopathy in diabetes mellitus. AB - The activities of urinary N-acetyl-beta-D-glucosaminidase (NAG) and alanine aminopeptidase (AAP) were measured in 207 diabetic patients and 57 healthy controls, and the relationship of these enzymes to different stages of diabetic microangiopathy was studied. Diabetics with clinical proteinuria had higher urinary NAG and AAP (17.7 +/- 1.9 and 42.8 +/- 4.9 U/g creatinine, mean +/- SE, respectively) than healthy controls (1.8 +/- 0.1 and 10.0 +/- 0.4) or diabetics without proteinuria. Among diabetics without proteinuria, NAG excretion in those with retinopathy was slightly higher than in those without (6.4 +/- 0.5 v 5.4 +/- 0.4), and AAP in those with retinopathy was significantly higher than in those without (23.0 +/- 1.5 v 17.4 +/- 0.8, P less than 0.01). Urinary albumin measured by radioimmunoassay and lysozyme in diabetics with retinopathy but without proteinuria was higher than those without retinopathy (P less than 0.001 and P less than 0.01). The increase in albumin was the greatest in diabetics with long duration of the disease (greater than or equal to 8 years); however, NAG and AAP increased more significantly in those with high hemoglobin A1c than in patients with long duration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881187 TI - Determination of adenylate cyclase and guanylate cyclase activities in cells of the immune system. PMID- 2881188 TI - Purification of brain microtubules and microtubule-associated protein 1 using taxol. PMID- 2881189 TI - Purification of microtubules and microtubule-associated proteins from sea urchin eggs and cultured mammalian cells using taxol, and use of exogenous taxol stabilized brain microtubules for purifying microtubule-associated proteins. PMID- 2881190 TI - Isolation of sea urchin spindles and cytasters. PMID- 2881191 TI - Viewing single microtubules by video light microscopy. PMID- 2881192 TI - Drugs for migraine. PMID- 2881194 TI - [Sensitivity of different species and different larval stages of mosquitoes to bacterial preparations]. PMID- 2881193 TI - Hydrophobic adherence and phase variation in Bordetella pertussis. AB - The hydrophobicity of Bordetella pertussis was assayed by measuring the ability of cells in suspension to adhere to a polystyrene surface. The quantity of adhered bacteria was measured by the binding of enzyme-conjugated anti B. pertussis antibodies. Hydrophobic adherence of non-pathogenic variant strains was about 20% of that exhibited by pathogenic strains. Hydrophobicity was a stable trait as it did not change with passaging or storage. Assays of a series of characterized stable variants suggested that the Filamentous Hemagglutinin (FHA) is the cell surface moiety responsible for hydrophobic adherence in B. pertussis. PMID- 2881195 TI - [Changes in hormonal counter-regulation following insulin-induced hypoglycemia with simultaneous administration of the somatostatin analog SMS 201-995]. PMID- 2881196 TI - Expression of hamster P-glycoprotein and multidrug resistance in DNA-mediated transformants of mouse LTA cells. AB - The overexpression of a plasma membrane glycoprotein, P-glycoprotein, is strongly correlated with the expression of multidrug resistance. This phenotype (frequently observed in cell lines selected for resistance to a single drug) is characterized by cross resistance to many drugs, some of which are used in cancer chemotherapy. In the present study we showed that DNA-mediated transformants of mouse LTA cells with DNA from multidrug-resistant hamster cells acquired the multidrug resistance phenotype, that the transformants contained hamster P glycoprotein DNA sequences, that these sequences were amplified whereas the recipient mouse P-glycoprotein sequences remained at wild-type levels, and that the overexpressed P-glycoprotein in these cells was of hamster origin. Furthermore, we showed that the hamster P-glycoprotein sequences were transfected independently of a group of genes that were originally coamplified and linked within a 1-megabase-pair region in the donor hamster genome. These data indicate that the high expression of P-glycoprotein is the only alteration required to mediate multidrug resistance. PMID- 2881199 TI - [Circulating somatostatin concentrations in childhood. Studies in normal weight and obese children and patients with growth hormone deficiency]. AB - At present in childhood there is only few information about the importance concerning circulating somatostatin concentrations. We therefore investigated the plasma somatostatin response to a mixed meal, an oral glucose load, pentagastrin injection and insulin hypoglycemia in normal weight and obese children and patients with growth hormone deficiency. Results in normal weight children: 1. Following a 800 kcal mixed meal (50% carbohydrate, 35% protein, 15% fet) peak values of plasma somatostatin were reached within 30-180 min (37.6 +/- 4.2 pg/ml vs. 58.5 +/- 3.4 pg/ml; p less than 0.05) in 6 children. 2. In response to oral glucose load of 1.75 g/kg bw glucose no alterations of plasma somatostatin levels were observed in 13 children 3. Injection of 6 micrograms/kg bw pentagastrin s.c. in 10 children resulted in maximal increase of somatostatin concentrations between 5 and 15 min (32.0 +/- 4.5 pg/ml vs. 69.1 +/- 7.4 pg/ml; p less than 0.01). 4. Injection of 0.1 IU/kg bw insulin in 7 children induced hypoglycemia and stimulated peak values of plasma somatostatin within 15-60 min (32.0 +/- 6.6 pg/ml vs. 57.4 +/- 6.4 pg/ml; p less than 0.01). - Results in obese children: Following mixed meal ingestion in 7 obese children plasma somatostatin response was comparable to controls. Although integrated insulin response over 180 min was higher in this group (9694 +/- 1363 microU/ml vs. 5054 +/- 651 microU/ml; p less than 0.05) the integrated somatostatin response (9038 +/- 1852 pg/ml) did not differ from controls (8614 +/- 876 pg/ml). After oral glucose load no changes in circulating somatostatin concentrations were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881198 TI - [Enzymuria and kidney diseases in childhood]. AB - Urinary enzyme excretion and proteinuria were studied in 316 children with different underlying diseases. Activities on N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase decreased progressively with age in the urine of 66 healthy prematures, newborns, infants or children. In 51 children with nephrotic syndrome, tubulopathies or chronic renal failure, excretion of NAG and AAP rose 3 to 30 fold. Contrary to molecular weight dependent protein analysis, determination of enzymuria did not allow to differentiate between glomerular and tubular disorders. After renal transplantation, 31 out of 52 children had a pathological enzymuria. NAG and AAP were more frequently elevated during treatment with cyclosporine A (21/29), than with azathioprine (10/23). The influence of nephrotoxic drugs upon enzymuria was documented in 14 children with cystic fibrosis or septicaemia treated with tobramycin. Activities of NAG and AAP rose transiently, whereas proteinuria remained almost unchanged. Only three out of 45 children receiving nonsteroidal antiinflammatory drug therapy for juvenile rheumatoid arthritis or spondylarthritis showed a pathological increase in enzymuria. Mean urinary NAG and AAP excretion in 154 children with insulin dependent diabetes mellitus were not different from controls and were unrelated to either duration of disease or HbA1 concentration. The determinations of urinary enzymes as non-invasive tests of renal integrity in medicine and toxicology provide a very sensitive indicator of renal damage. The assays of NAG and AAP have proven to be most valuable; however, due to a lack of specificity for the type and origin of renal dysfunction, these urinary enzyme assays are most useful when carried out in conjunction with electrophoretic analyses of proteinuria. PMID- 2881197 TI - Different functional domains of the adenovirus E1A gene are involved in regulation of host cell cycle products. AB - We have analyzed the cell cycle effects that different domains of the adenovirus E1A proteins have on quiescent primary BRK cells. Studies with deletion mutants that in combination removed all but the N-terminal 85 amino acids common to both the 12S and 13S proteins suggest that this region may be sufficient for the induction of synthesis of proliferating cell nuclear antigen and the stimulation of DNA synthesis. A second domain also common to the N-terminal exon of the 12S and 13S proteins was required for the induction of mitosis and stimulation of proliferation of primary BRK cells. A virus containing a mutation in this region was still able to stimulate DNA synthesis efficiently. A third domain, unique to the 13S protein, was required for the accelerated activation of the cellular thymidylate synthase gene in a manner similar to the 13S-dependent stimulation of adenovirus early region genes. PMID- 2881200 TI - [Electric potential of soldered gold crown bridges in the mouth]. PMID- 2881201 TI - The nature of radiation-induced mutations at the white locus of Drosophila melanogaster. AB - X-Ray- and neutron-induced mutations at the white locus of Drosophila melanogaster were used to study the nature of radiation-induced genetic damage. Genetic analysis showed the presence of multi-locus deficiencies in 15 out of 31 X-ray mutants and in 26 out of 35 mutants induced by neutrons. The DNA from 11 X ray and 4 neutron mutants, which were not multi-locus deficiencies, was analyzed by Southern blot-hybridization. Deletions were observed in 2 X-ray and 1 neutron mutant. In combination with cytogenetic techniques, chromosomal rearrangements affecting the white locus (translocations, inversions, etc.) were identified in 3 X-ray and in 2 neutron mutants. A hot-spot for translocation breakpoints was identified in the left arm of the third chromosome. 5 X-ray mutants, which apparently did not contain large deletions, were subjected to further analysis by the nuclease S1 protection method, after cloning of the white gene. In 4 mutants a small deletion could indeed be detected in this way. Thus it seems that by far the main part of X-ray- and neutron-induced white mutants have arisen through large changes in the white gene, especially deletions. PMID- 2881202 TI - Formation of a highly mutagenic diazo compound from the bamethan-nitrite reaction. AB - A variety of cardiovascular drugs were treated with 10 equivalent amounts of nitrite in acidic solutions. Among 18 drugs, a preparation of bamethan [1-(4 hydroxyphenyl)-1-hydroxy-2-butylaminoethane] showed strikingly high mutagenicity by this treatment toward Salmonella typhimurium TA98 and TA100 strains. Treatment of bamethan with an equivalent amount of nitrite gave N-nitrosobamethan I which was not mutagenic. However, treatment of bamethan with 4 equivalent amounts of nitrite afforded a highly mutagenic compound II, which was identified as 3-diazo N-nitrosobamethan by its physicochemical analysis and chemical properties. Specific mutagenic activity of II was 9200 His+ revertants/mu mole toward TA98 and 8060 His+ revertants/mu mole toward TA100. Addition of microsomal system little affected the activity. Bamethan is administrated orally during long period for treatment of cardiovascular diseases. It is noted that this drug can produce the highly mutagenic diazo compound by reaction with nitrite which is present in digestive tracts. PMID- 2881204 TI - Absence of mutagenic activity of benorylate, paracetamol and aspirin in the Salmonella/mammalian microsome test. AB - Benorylate and its two major hydrolysis products, paracetamol and aspirin were examined for mutagenicity in the Salmonella/mammalian microsome screening test. The compounds were tested in 6 strains of Salmonella typhimurium (TA1535, TA1537, TA1538, TA100, TA97 and TA98) in the presence and absence of a rat-liver microsome activation system. Benorylate did not show evidence of mutagenic activity in the 6 strains tested with or without metabolic activation at concentrations ranging from 0.006 to 3 mg per plate. Paracetamol and aspirin likewise did not show any evidence of mutagenic activity at concentrations ranging from 0.1 to 50 mg per plate for the former and 0.01 to 50 mg per plate for the latter. PMID- 2881203 TI - Glutathione mutagenesis in Salmonella typhimurium TA100: dependence on a single enzyme, gamma-glutamyltranspeptidase. AB - Glutathione was mutagenic in Salmonella typhimurium strain TA100 in the presence of purified mammalian gamma-glutamyltranspeptidase. Glutathione disulfide, gamma glutamyl glutamic acid, and S-methyl-glutathione were not mutagenic under the same conditions. Glutathione-mediated, gamma-glutamyltranspeptidase-dependent mutagenesis of TA100 cells was inhibited by serine-borate complex, a known gamma glutamyltranspeptidase inhibitor, and potentiated by glycylglycine, a known gamma glutamyltranspeptidase enhancer. It is concluded that this enzyme is necessary and sufficient to activate glutathione to a mutagen. PMID- 2881205 TI - Antiamebic antibodies in homosexual men. PMID- 2881206 TI - Reversibility of catecholamine-induced dilated cardiomyopathy in a child with a pheochromocytoma. PMID- 2881207 TI - The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. AB - Alzheimer's disease is characterized by a widespread functional disturbance of the human brain. Fibrillar amyloid proteins are deposited inside neurons as neurofibrillary tangles and extracellularly as amyloid plaque cores and in blood vessels. The major protein subunit (A4) of the amyloid fibril of tangles, plaques and blood vessel deposits is an insoluble, highly aggregating small polypeptide of relative molecular mass 4,500. The same polypeptide is also deposited in the brains of aged individuals with trisomy 21 (Down's syndrome). We have argued previously that the A4 protein is of neuronal origin and is the cleavage product of a larger precursor protein. To identify this precursor, we have now isolated and sequenced an apparently full-length complementary DNA clone coding for the A4 polypeptide. The predicted precursor consists of 695 residues and contains features characteristic of glycosylated cell-surface receptors. This sequence, together with the localization of its gene on chromosome 21, suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor. PMID- 2881208 TI - Molecular genetics of the mind. PMID- 2881209 TI - Bipolar affective disorders linked to DNA markers on chromosome 11. AB - An analysis of the segregation of restriction fragment length polymorphisms in an Old Order Amish pedigree has made it possible to localize a dominant gene conferring a strong predisposition to manic depressive disease to the tip of the short arm of chromosome 11. PMID- 2881210 TI - Molecular genetic evidence for heterogeneity in manic depression. AB - Manic depression is a severe cyclic mental illness that can be unipolar or bipolar and has a lifetime risk of approximately 7 per 1,000 in most populations. Families with multiple cases of manic depression have been described that are compatible with both autosomal dominant and X-linked modes of genetic transmission. Psychoactive antidepressant and stimulant drugs that help to ameliorate depression and mania are thought to act by affecting catecholamine neurotransmitter systems such as adrenaline, noradrenaline and dopamine, amongst others. Mutations affecting the tyrosine hydroxylase (TH) gene, which encodes the rate-limiting enzyme for the synthesis of these three neurotransmitters, might therefore be responsible for causing the manic depressive phenotype. We have studied three Icelandic kindreds amongst whom it appears that a single autosomal dominant disease allele is segregating. In these families there were 44 cases amongst 73 individuals at risk. Genetic linkage studies were carried out using clones encoding tyrosine hydroxylase the variable portion of the Harvey-ras-1 (HRAS1) locus and the variable region of the insulin gene (INS). All three markers are closely linked on chromosome 11 and were used to observe the segregation of restriction fragment length polymorphisms (RFLPs) in the three affected kindreds. We found no evidence for linkage to these markers in any of the three families. In contrast, Gerhard et al. found linkage between manic depression and HRAS1 in a single large Amish kindred. We conclude that there is genetic heterogeneity of linkage in manic depression. Therefore mutations at different loci are responsible for the manic depressive phenotype in the Amish and in Iceland. PMID- 2881211 TI - Ligand binding to the beta-adrenergic receptor involves its rhodopsin-like core. AB - Recently the genes for several hormone receptors that interact with guanine nucleotide binding proteins (G proteins) have been cloned, including the hamster beta 2-adrenergic receptor (beta 2AR), a human beta AR, the turkey erythrocyte beta AR and the porcine muscarinic acetylcholine receptor (MAR). All these receptors share some amino-acid homology with rhodopsin, particularly in 7 hydrophobic stretches of residues that are believed to represent transmembrane helices. To determine whether differences in ligand specificity result from the divergence in the sequences of the hydrophilic regions of these receptors, we have expressed in mammalian cells genes for the wild-type hamster and human beta AR proteins, and a series of deletion mutant genes of the hamster beta 2AR. The pharmacology of the expressed receptors indicates that most of the hydrophilic residues are not directly involved in the binding of agonists or antagonists to the receptor. In addition, we have identified a mutant receptor that has high agonist affinity but does not couple to adenylate cyclase. PMID- 2881212 TI - Linkage of an X-chromosome cleft palate gene. AB - Many congenital malformations, such as cleft palate and neural tube defects, have a multifactorial origin involving both environmental and genetic factors. Conditions such as these may be exclusively monogenic, polygenic or environmental, but in most cases both genetic and environmental factors are involved. This study describes the sub-chromosomal localization of a single gene defect causing cleft palate and ankyloglossia (tongue-tied) in a large Icelandic family. This defect is a model for the analysis of other neural-crest malformations that show a more complex multifactorial inheritance pattern. PMID- 2881213 TI - Homozygotes for Huntington's disease. AB - Careful comparison of symptomatic individuals with normal controls has revealed the primary biochemical abnormality in many human genetic diseases, particularly recessive disorders. This strategy has proved less successful for most human disorders which are not recessive, and where a single copy of the aberrant gene has clinically significant effects even though the normal gene product is present. An alternative approach that eliminates the impediment of a normal protein in affected individuals is to study homozygotes for the mutant allele. For virtually all dominant human disorders in which homozygotes have been described, symptoms have been significantly more severe in the homozygote than in the heterozygote. Thus, these disorders do not conform to the classical definition of dominance which states that homozygotes and heterozygotes for a defect are phenotypically indistinguishable. Instead, they display incomplete dominance, indicating that the normal allele may play a role in ameliorating the disease process. The D4S10 locus, defined by the probe G8 and linked to the gene for Huntington's disease (HD), has permitted us to identify individuals with a high probability of being homozygous for this autosomal dominant neurodegenerative disorder. These homozygotes do not differ in clinical expression or course from typical HD heterozygotes. HD appears to be the first human disease of genetically documented homozygosity that displays complete phenotypic dominance. PMID- 2881214 TI - A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans. AB - Twenty-three genes have been assigned to particular steps in a genetic pathway for the specification of the vulval cell lineages of the nematode Caenorhabditis elegans. Mutations in most of these genes cause homoeotic transformations in the fates of individual cells, suggesting that these lineages may be specified by a series of decisions that distinguish between alternative cell fates. Fifteen of the genes function in a system involved in the intracellular response to the extracellular signal that induces vulval formation. PMID- 2881215 TI - Release of [3H]acetylcholine from a modified rat phrenic nerve-hemidiaphragm preparation. AB - Two different preparations of the rat phrenic nerve-hemidiaphragm (whole nerve muscle preparation, end-plate preparation) were used for studying synthesis and release of radioactive acetylcholine in the absence and presence of cholinesterase inhibitors. When the whole nerve-muscle preparation (110-180 mg) was incubated with [3H]choline, only small amounts of radioactive acetylcholine were synthesized within the tissue. Electrical nerve stimulation of the whole nerve-muscle preparation produced no increase in tritium outflow. Incubation of the end-plate preparation (16-29 mg) which was obtained after removal of most of the muscle mass led to the formation of large amounts of [3H]acetylcholine. Synthesis depended on nerve activity and increased 13-fold during a high loading stimulation (50 Hz), as compared to the synthesis at rest. In a denervated end plate preparation the formation of [3H]acetylcholine was reduced to 4% of the control preparation. Electrical nerve stimulation of the end-plate preparation produced a release of tritium that could be attributed entirely to the release of [3H]acetylcholine. The stimulated tritium efflux was completely suppressed in a calcium-free medium or in the presence of tetrodotoxin (300 nM). Release could even be detected during a short train of 50 pulses (5 Hz) with a fractional release of about 0.04% of the [3H]acetylcholine tissue content per pulse. It is concluded that the large muscle mass interferes with nerve labelling by a reduction of the [3H]choline supply to the nerve terminals when the whole nerve muscle preparation is used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881216 TI - Presynaptic nicotine receptors mediating a positive feed-back on transmitter release from the rat phrenic nerve. AB - The effects of 1,1-dimethyl-4-phenylpiperazinium (DMPP) and of nicotine receptor antagonists on [3H]acetylcholine release from the rat phrenic nerve preincubated with [3H]choline were investigated in the absence and presence of cholinesterase inhibitors (presynaptic effects). Additionally, the effects of hexamethonium and tubocurarine on the muscle contraction of the indirectly stimulated diaphragm were examined (postsynaptic effects). DMPP (1-30 microM) increased (76-92%), whereas hexamethonium (0.001-1 mM) and tubocurarine (1-10 microM) decreased (52 60%) the release of [3H]acetylcholine following a train of 100 pulses at 5 Hz. The release caused by a longer train (750 pulses at 5 Hz) was only slightly affected by DMPP and tubocurarine. In the presence of neostigmine (10 microM) neither tubocurarine nor DMPP significantly modulated the evoked [3H]acetylcholine release. High DMPP concentrations (10 and 30 microM) enhanced the evoked release only when the pretreatment interval was reduced from 15 min to 20 s. Tubocurarine and hexamethonium concentration-dependently inhibited the end organ response. Hexamethonium was 250-fold more potent on presynaptic than on postsynaptic nicotine receptors. It is concluded that the motor nerve terminals are endowed with presynaptic nicotine receptors. These autoreceptors mediate a positive feed-back mechanism that can be triggered by previously released endogenous acetylcholine. Receptor desensitization can be produced by high agonist concentrations (endogenous or exogenous agonists) and is probably one mechanism to limit the autofacilitatory process. The presynaptic receptors appear to differ in their pharmacological properties from the postsynaptic receptors. PMID- 2881217 TI - Some pharmacological properties of Wy 27127 a more selective alpha 2:alpha 1 adrenoceptor antagonist than idazoxan in vitro. AB - Wy 27127 and idazoxan were approximately equipotent as antagonists at alpha 2 adrenoceptors as estimated by their ability to block clonidine-induced inhibition of electrically-evoked contractions of the rat isolated vas deferens. Idazoxan was seven times as potent as Wy 27127, as an antagonist at alpha 1-adrenoceptors as indicated by blockade of methoxamine-induced contractions of the rat isolated anococcygeus muscle. Thus, the alpha 2:alpha 1 selectivity ratio, as calculated from these tests was 407 for Wy 27127 and 76 for idazoxan. Wy 27127 and idazoxan were equipotent in enhancing stimulation-evoked overflow of tritium from rabbit isolated pulmonary arteries preloaded with [3H]-noradrenaline as expected for alpha 2-adrenoceptor antagonists. At higher concentrations both compounds reduced the stimulation-evoked contraction of the pulmonary artery but idazoxan was 15 times as potent as Wy 27127 in this respect. Neither compound had marked antagonist actions at 5-hydroxytryptamine (D), muscarinic, presynaptic dopamine or histamine (H1) receptors or at beta 1-adrenoceptors. Thus, idazoxan and Wy 27127 were equipotent alpha 2-adrenoceptor antagonists in vitro, however, the alpha 2:alpha 1 selectivity of Wy 27127 was considerably greater than that of idazoxan by virtue of weaker alpha 1-adrenoceptor antagonism. PMID- 2881220 TI - [Possibilities and impossibilities in the treatment of young children with CARA]. PMID- 2881221 TI - [The course of the first schizophrenic illness. A 5-year catamnesis]. PMID- 2881218 TI - Alpha-adrenoceptor activity of arylalkylimidazoles is improved by alpha methylation and impaired by alpha-hydroxylation. AB - To investigate the effects of hydroxyl and methyl substitution of the alkyl bridge bond on the alpha-adrenoceptor activity of arylalkylimidazole derivatives, the cardiovascular effects of the molecules were studied in anaesthetized and pithed rats. The compounds studied were 4(5)-substituted imidazole derivatives with a methano, ethano or etheno bridge between the imidazole and the 2-, 2,3- or 2,6-methyl substituted phenyl rings. The hypotensive and bradycardic activities of the molecules in the anaesthetized rat were always reduced by alpha hydroxylation and usually augmented by alpha-methylation of the bridge between the imidazole and phenyl rings. Hydroxylation was associated with a consistent, marked decrease in vasopressor and sympatho-inhibitory activity in the cardiovascular system of the pithed rat, but a methyl moiety as a "bulky substituent" in the alpha-position of the alkyl bridge did not decrease but even caused an increase in alpha-adrenoceptor activity in this test system. The detrimental effect of alpha-hydroxylation of the compounds at alpha 1- and alpha 2-adrenoceptors supports the notion that the interaction of the imidazoles at alpha-adrenoceptor is different from that of the classical, noradrenaline-like phenethylamines. The results also suggest that the alkyl bridge between the phenyl and imidazole rings of the imidazoles may contribute directly to the binding process. PMID- 2881219 TI - The effect of age on the sensitivity of pre- and postsynaptic alpha-adrenoceptors to agonists and antagonists in the rat. AB - Age-related changes in presynaptic alpha-2 and postsynaptic alpha-1 adrenoceptors have been determined using the rat isolated vas deferens and the thoracic aorta, respectively. The IC50 values of clonidine, B-HT 933 and UK 14,304 for inhibition of the electrically evoked contractions of the vas deferens were significantly higher in 50 week old rats when compared with rats of 5 weeks. Similarly, EC50 values for the contraction of the thoracic aorta by noradrenaline, methoxamine and phenylephrine were significantly increased in 50 week old rats compared with 5 week old rats. No age-related changes in the potency of the selective alpha-2 adrenoceptor antagonists yohimbine and Wy 26392 were detected in the vas deferens. Similarly, there were no age-related changes in the alpha-1 adrenoceptor antagonist potency of indoramin or prazosin on the aorta. The results of the present study suggest that the potency of both alpha-1 and alpha-2 adrenoceptor agonists, as measured by their respective EC and IC50 values decreases with increasing age. PMID- 2881223 TI - Electrophysiological evidence for a sex difference in neural regulation of prolactin secretion in rats. AB - Prolactin (PRL) secretion patterns were determined in freely moving male and female rats chronically fitted with electrodes in the sexually dimorphic component of the medial preoptic area (MPOA) and the median eminence (ME), together with a chronic atrial blood sampling catheter. Electrodes made of stainless steel or platinum-iridium were implanted bilaterally. Female rats with 4 electrodes in the ME exhibited an attenuated surge of PRL secretion on proestrus (injured group), rats with 2 electrodes in the ME had a normal proestrous surge (intact group). Basal PRL levels were not different between the two groups. Stimulation (100-Hz voltage pulses, 0.2 ms width, 10 s on/5 s off, total duration 25 min) did not produce lesions. Evidence is presented that experimentation was performed without stress. Electrical stimulation applied to the MPOA increased PRL secretion in males, decreased PRL secretion in proestrous females and was without effect in conscious or anesthetized diestrous females. Electrical stimulation applied to different locations of the ME was without effect in male and diestrous female rats; it reduced PRL secretion in proestrous females. These data demonstrate that the MPOA has a sexually differentiated function in the regulation of PRL secretion. The data do not provide evidence for a sexual dimorphism in prolactin-inhibiting factor and prolactin-releasing factor activity in the ME. PMID- 2881222 TI - Release studies related to the neurotransmitter role of glutamate in the cerebellum: an overview. PMID- 2881225 TI - Computed tomographic myelography in spinal subdural empyema. PMID- 2881224 TI - The effect of mu, delta, kappa and epsilon opioid receptor agonists on heart rate and blood pressure of the pithed rat. AB - Opioid peptides and opioid receptors are found in the hearts of various species. Opioid peptides were also shown to modulate norepinephrine inducing changes in atrial rate, in vitro. Since we have recently shown a predominance of kappa and delta receptors in the rat atria, we found it of interest to study the role of highly selective opioid agonists on spontaneous and sympathetically stimulated heart rate. The pithed, artificially ventillated rat was used in these studies. D Ala2-D-Leu5-enkephalin (DADL), was used as an delta-agonist, D-Ala2-MePhe4-Gly ol5-enkephalin (DAGO) as a highly selective mu-agonist; Dynorphin A (1-17) as a kappa-agonist and beta-endorphin (beta-END) as a mixed epsilon-delta-mu agonist. Naloxone was used as an opiate antagonist. None of the above opioid peptides changed the basal blood pressure and heart rate at 1-100 nmol/kg except Dyn A-(1 17) which produced a brief depressor response (-15 +/- 2 mmHg, p less than 0.01). Stimulation of the spinal cord (50 v, 1 msec, 1 Hz, 30 sec) produced consistant pressor and cardiac accelerating responses. None of the opioid peptides studied blocked or enhanced the increase in blood pressure or heart rate produced by spinal cord stimulation. The depressor effect of the high dose of Dyn A-(1-17) was not blocked by naloxone. These results suggest that mu, delta or kappa opioid receptors in the rat heart have no role in the regulation of basal or sympathetically driven heart rate. Our data also suggest no role for these opioid receptors in modulation of basal arterial tone or norepinephrine-induced arteriolar constriction. PMID- 2881226 TI - Quantification of immunogold labelling reveals enrichment of glutamate in mossy and parallel fibre terminals in cat cerebellum. AB - The glutamate immunoreactivity of different cell populations was compared quantitatively in the cerebellar cortex of cat, using an antiserum raised against glutamate coupled to bovine serum albumin by glutaraldehyde. Neuronal and glial processes were identified on serial electron microscopic sections which were processed by a postembedding immunogold procedure. The surface density of colloidal gold particles was used for statistical comparison of the relative levels of glutamate in cell populations, or in different parts of the same population. The terminals of mossy and parallel fibres had significantly higher levels of glutamate immunoreactivity than Golgi cell terminals, granule cell dendritic digits, Purkinje cell dendrites or dendritic spines. Golgi cell terminals were identified by their position and GABA immunoreactivity as revealed by immunogold in serial sections. The dendritic digits of the putative glutamatergic granule cells had significantly higher glutamate immunoreactivity than did Purkinje cell dendrites and dendritic spines. Glial cell processes in the molecular layer had lower level of glutamate immunoreactivity than any of the neuronal processes. The results demonstrate that the highest levels of glutamate immunoreactivity occur in mossy and parallel fibre presynaptic terminals that are known to have an excitatory effect. This supports previous suggestions that glutamate may be a transmitter at these synapses. The measurement of the levels of putative amino acid transmitters in identified neuronal populations, or in different parts of the same population, could have wide applications in studies on the chemical neuroanatomy of the nervous system. PMID- 2881227 TI - In vivo presynaptic control of dopamine release in the cat caudate nucleus--II. Facilitatory or inhibitory influence of L-glutamate. AB - The local effects of various concentrations of L-glutamate (from 10(-8) M up to 10(-3) M) on the release of [3H]dopamine synthesized continuously from [3H]tyrosine were examined in the caudate nucleus of halothane-anaesthetized cats implanted with push-pull cannulae. When used at a concentration of 10(-8) M or 10(-7) M, L-glutamate stimulated the release of [3H]dopamine from nerve terminals of the nigrostriatal dopamine neurons. This effect was still observed in the presence of tetrodotoxin (5 X 10(-7) M) but it was antagonized by 2-amino 6 trifluoromethoxy benzothiazole (PK 26124) (10(-5) M), an antagonist dopamine nerve terminals. While no significant change in the release of [3H]dopamine was observed with 10(-6) M L-glutamate, higher concentrations (from 10(-5) M to 10( 3) M) of the amino acid produced a long-lasting reduction in the [3H]transmitter release. This latter effect was also antagonized by PK 26124 (10(-5) M) but, unlike that observed with 10(-8) M L-glutamate, it did not persist in the presence of tetrodotoxin (5 X 10(-7) M). On the contrary, a marked stimulation of the release of [3H]dopamine was seen in the presence of this neurotoxin. The reduction in the release of [3H]dopamine produced by 10(-4) M L-glutamate was also antagonized by bicuculline (10(-5) M) and moreover a marked stimulation of [3H]dopamine release took place in the presence of this gamma-aminobutyric acid (GABA) antagonist. Therefore, high concentrations of L-glutamate exerted an inhibitory presynaptic control on [3H]dopamine release which seemed to be indirect and mediated partly by GABAergic neurons. Since a sustained reduction in the spontaneous release of [3H]dopamine was seen in the presence of PK 26124, the corticostriatal glutamatergic neurons appeared to exert a tonic facilitatory presynaptic influence on dopamine release. This effect was important since it represented 40% of the tetrodotoxin-sensitive release of the [3H]transmitter. The direct (stimulatory) and indirect (inhibitory) presynaptic controls on dopamine release mediated by corticostriatal glutamatergic fibres are discussed in light of previous findings and of the anatomical organization of the caudate nucleus. PMID- 2881228 TI - In vivo presynaptic control of dopamine release in the cat caudate nucleus--III. Further evidence for the implication of corticostriatal glutamatergic neurons. AB - In confirmation of previous results, experiments in halothane-anaesthetized cats implanted with push-pull cannulae showed that the unilateral application of GABA (10(-5) M for 30 min) into the left thalamic motor nuclei (either ventralis medialis, or ventralis lateralis) markedly stimulated the release of [3H]dopamine continuously synthesized from [3H]tyrosine in both caudate nuclei and in the contralateral substantia nigra. Three types of experiments confirmed that the changes in [3H]dopamine release evoked in both caudate nuclei resulted from a presynaptic facilitation mediated by the bilateral corticostriatal glutamatergic projection: The constant delivery of 2-amino 6-trifluoromethoxy benzothiazole (PK 26124) (10(-5) M) to the left caudate nucleus prevented the increased release of [3H]DA evoked by application of gamma-aminobutyric acid (GABA) (10(-5)M) into ventralis medialis-ventralis lateralis while an enhanced release of [3H]dopamine still occurred in the contralateral caudate nucleus. Since PK 26124 is an antagonist of glutamatergic transmission, the presynaptic facilitation may involve glutamatergic neurons. Single unit recordings of dopamine cells in the contralateral substantia nigra indicated that the increased release of [3H]dopamine from dendrites evoked by the application of GABA (10(-5)M) into ventralis medialis-ventralis lateralis was associated with a reduction in the firing rate of dopamine cells. Thus, the enhanced release of [3H]dopamine in the contralateral caudate nucleus may involve a presynaptic facilitatory process. Finally, the unilateral lesion of the sensory motor cortex made prior to the superfusion of caudate nucleus with [3H]tyrosine prevented the responses evoked in the two caudate nuclei by the application of GABA (10(-4) M) into ventralis medialis-ventralis lateralis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881229 TI - Effects of intracerebroventricular AF64A administration on cholinergic, serotoninergic and catecholaminergic circuitry in rat dorsal hippocampus. AB - Five nmol ethylcholine mustard aziridinium ion, a potential cholinotoxin was administered bilaterally into the cerebral ventricles of male rats at coordinates A -1.5, L +/- 1.5 and V -4.0 mm. The dorsal hippocampi were processed for choline acetyltransferase, serotonin or tyrosine hydroxylase immunocytochemistry 7 days after the injection to determine the specificity of the effect of the drug. Intrinsic choline acetyltransferase positive cells were also found after treatment, while the overall staining of fibres decreased. No change was observed in staining for either serotonin or tyrosine hydroxylase. Using the electron microscope, degenerating nerve terminals, with recognizable synaptic specializations were encountered, most frequently in stratum oriens and occasionally, degenerated CA3 pyramidal cells were observed. These findings are consistent with the neurochemical data obtained in parallel experiments with the morphological study in which it was found that acetylcholine content of the hippocampus was reduced by 73.4% 7 days after ethylcholine mustard aziridinium ion treatment, while dopamine, noradrenaline and serotonin levels were unaffected. Furthermore, the morphological studies indicate that ethylcholine mustard aziridinium ion can exert selective effects on the cholinergic system of dorsal hippocampus without significantly altering its cytoarchitecture. PMID- 2881230 TI - [Association between medullary carcinoma of the thyroid and pathology of the parathyroid glands. Pathogenetic significance, diagnosis and treatment in a series of 13 patients]. PMID- 2881231 TI - Patient-controlled analgesia: a case study. PMID- 2881233 TI - Abstracts of the eight annual conference of the Hong Kong Society of Neurosciences. Hong Kong, September 4-5, 1986. PMID- 2881234 TI - Abstracts of the fifth meeting of the Brain Research Association. Edinburgh, Scotland, U.K., March 29-April 1, 1987. PMID- 2881232 TI - Excitatory amino acid receptors and ischemic brain damage in the rat. AB - The excitatory amino acid glutamate has been suggested to be an important mediator of the selective CA1 hippocampal damage which follows transient cerebral ischemia. In order to evaluate the possible involvement of altered glutamate receptor regulation in the expression of the delayed neuronal necrosis following ischemia, we have determined the density of glutamate receptor subtypes in the rat hippocampus following transient ischemia. We report a transient reversible decrease in [3H]AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) binding sites (presumably representing quisqualate receptors) followed by a long term loss of binding at 2 days postischemia which precedes neuronal loss. In contrast, no change was noted in the N-methyl-D-aspartate or kainic acid binding sites over this time period. PMID- 2881235 TI - Lead nitrate induced changes in the brain constituents of the freshwater fish Clarias batrachus (L). AB - Exposure of C batrachus to 5 ppm lead nitrate for 150 days resulted in the significant elevation of brain histamine and serotonin content, but Gamma aminobutyric acid level showed a decrease. Lead significantly reduced the brain monoamine oxidase and acetylcholinesterase activity. In addition, lead significantly lowered the brain lipid, cholesterol, protein and ascorbic acid contents. These findings suggest that lead significantly impairs the brain neurotransmitter function. PMID- 2881236 TI - The effect of trimethyltin on three glutamergic and gabaergic transmitter parameters in vitro: high affinity uptake, release and receptor binding. AB - The effects of trimethyltin (TMT) on high-affinity uptake, release and sodium independent binding of glutamic acid and gamma-aminobutyric acid (GABA) were studied in vitro in homogenates of hippocampal tissue. TMT (50 micron) increased the release of glutamic acid from synaptosomes in the resting state (5 mM K+), whereas the release of GABA was only slightly affected. High affinity uptake of glutamate was inhibited by TMT in the same concentration range as release. The uptake of GABA was only affected by TMT-concentrations from 500 micron to 5 mM. The sodium independent binding of both glutamate and GABA, usually assumed to be binding to receptor sites, were inhibited with 50 microM or more TMT in the incubation medium. The results indicate that TMT can interfere with several different events of the neurotransmission process in the central nervous system at concentrations which can be obtained in the brain of rats after a sublethal dose of the compound. PMID- 2881237 TI - Alpha-linolenic acid deficiency in adult women. PMID- 2881238 TI - T-cell leukaemia not confirmed. PMID- 2881239 TI - [Peptidases of oral Streptococci--II. Purification and characterization of dipeptidyl peptidase IV from Streptococcus salivarius HHT]. PMID- 2881240 TI - [Microbiologic diagnosis of whooping cough at public health offices in West Germany--results of a survey]. PMID- 2881242 TI - [Abnormalities of testis-epididymis fusion associated with undescended testis]. PMID- 2881241 TI - Mucocutaneous pigmented spots and oral myxomas: the oral manifestations of the complex of myxomas, spotty pigmentation, and endocrine overactivity. AB - The complex of myxomas, spotty pigmentation, and endocrine overactivity is a recently recognized syndrome, transmitted as an autosomal dominant trait. The most serious component of the disorder is cardiac myxoma, which has caused the death of one fourth of the affected patients and serious disability in an equal number. It is, therefore, important to recognize patients at risk from the syndrome and, in particular, to test them for cardiac myxoma. Fortunately, in many patients the myxoma complex has a clearly visible marker: mucocutaneous pigmentation. Among 58 patients with the syndrome, spotty facial pigmentation was present in 36 (62%), and 29 (50%) of these also had pigmented spots on their lips. This type and distribution of pigmentation should be a clue to the possible presence of the complex of myxomas, spotty pigmentation, and endocrine overactivity, and patients thus affected should be referred for further investigation. Oral cavity myxoma(s) occurred in four patients with the syndrome. PMID- 2881243 TI - [Effect of blockade of adrenergic beta receptors on the development of disorders of cardio- and hemodynamics in shock of immunologic origin]. PMID- 2881244 TI - Spermatic venography in undescended testes. AB - In patients with undescended testes the demonstration of the pampiniform plexus (i.e. venous network surrounding the testis) by selective retrograde contrast filling of the internal spermatic vein gives exact information about the existence and localization of the gonadal tissue. Especially with small hypoplastic testes and/or an intraabdominal position of the gonad the results of this technique are superior to those of ultrasound and computed tomography. The venographic information often helps to reduce the extent of the surgical exploration, most of all in those cases in which after an ineffective first procedure a second operation is planned. Venography can be done on an outpatient basis in children from an age of about 6 years upwards without general anesthesia and serious complications. Personal experiences with the spermatic venography in 11 patients (age: 7-32 years) with 18 undescended testes are demonstrated. Comparing the roentgenologic and surgical findings in 7 patients with 12 explored veins the results corresponded completely in 75%. In the remaining cases roentgenologic demonstration of one of the testicular veins with its pampinifom plexus suggested important information about the localization of the contralateral testis, surgically confirmed later. PMID- 2881245 TI - Acetoacetyl CoA thiolase deficiency presenting as ketotic hypoglycemia. AB - We report two children who presented with hypoglycemia and metabolic acidosis in whom acetoacetyl-CoA thiolase (EC 2.3.1.9) measured in fibroblast homogenates was deficient. Deficiency of this enzyme is normally associated with urinary excretion of 2-methylacetoacetate and in one child the urinary excretion of 2 methylacetoacetate, 2-methyl-3-hydroxybutyrate, and tiglylglycine was raised. By contrast, in the other child, the urinary excretion of these metabolites was very low even during ketoacidosis and following an isoleucine load. We suggest that this could be due to deficiency of the extrahepatic isoenzyme, a defect that may be responsible for some of the cases of "ketotic hypoglycemia." PMID- 2881246 TI - Measles virus in the cerebrospinal fluid in postvaccination immunosuppressive measles encephalopathy. PMID- 2881247 TI - Phosphate transport across the basolateral membrane from rat kidney cortex: sodium-dependence? AB - Basolateral membrane vesicles were isolated from rat renal proximal tubules by a Percoll-centrifugation method. Transport of phosphate could be stimulated by a sodium gradient but transport of D-glucose was not or only slightly affected by sodium. The Percoll-basolateral membrane fraction showed sodium-independent trans stimulation of phosphate by itself. To test whether sodium stimulation of phosphate transport is influenced by the crosscontamination of basolateral with brush border membranes, the basolateral membrane fraction obtained by the Percoll method was applied to free-flow electrophoresis for further purification. Thereby a separation of basolateral from brush border marker enzymes was obtained. It was possible to correlate net sodium-dependent phosphate transport with the brush border marker enzyme activity. ATP-dependent calcium uptake and cytochalasin B sensitive, sodium-independent D-glucose uptake followed basolateral, whereas phlorizin sensitive, sodium-dependent D-glucose followed brush border marker enzymes. Sodium dependent phosphate uptake was inhibited by D-glucose, this inhibition was released by phlorizin. It is concluded that the sodium-dependent phosphate uptake present in the Percoll-basolateral membrane fraction is due to crosscontamination with brush border membranes and that phosphate translocation across the basolateral membrane is carrier-mediated and sodium-independent. PMID- 2881248 TI - Proton pump activity and Mg-ATPase activity in rat kidney cortex brushborder membranes: effect of 'proton ATPase' inhibitors. AB - In order to further characterize the ATP driven proton pump present in the luminal membrane of the renal proximal tubule, brushborder membranes were isolated from rat kidney cortex and the effect of various proton ATPase inhibitors on intravesicular ATP hydrolysis in sealed brushborder membrane vesicles and on Mg-ATPase activity in permeabilized brushborder membranes was investigated. The protonophor induced intravesicular ATP hydrolysis (ATP driven proton pump) was inhibited by DCCD and filipin but not by diethylstilbestrol and duramycin. All four compounds decreased Mg-ATPase activity, the two former inhibited the ATPase activity with a lower potency than the proton pump. NEM--up to 10 mM--and orthovanadate did not affect intravesicular ATP hydrolysis nor Mg ATPase activity. From the relative sensitivity of the proton pump and the Mg ATPase activity to the inhibitors it is concluded that about 35% of the Mg-ATPase activity found in the brushborder membrane can be attributed to the ATP-driven proton pump. Furthermore, the results obtained with NEM and duramycin suggest that the brushborder membrane proton pump has different properties than the proton pump in clathrin-coated vesicles or endosomes. The results presented above raise the possibility that the brushborder membrane proton pump is predominantly involved in acid secretion by the proximal convoluted tubule whereas the proton pump in clathrin-coated vesicles may be predominantly involved in the endocytosis of larger peptides and proteins. PMID- 2881250 TI - [Enterocutaneous intestinal fistulas. Results with traditional and new therapeutic principles]. PMID- 2881249 TI - Ammoniagenesis catalyzed by hippurate-activated gamma-glutamyltransferase in the lumen of the proximal tubule. A microperfusion study in rat kidney in vivo. AB - gamma-Glutamyltransferase (gamma-GT) is located in the brushborder membrane of the proximal tubule where the catalytic site of the enzyme faces the lumen. The (phosphate-independent) glutaminase activity of gamma-GT in vitro is activated by hippurate. In order to investigate glutamine deamidation in the tubule lumen in vivo, 14C-L-glutamine-containing solutions were continuously microperfused through sections of the proximal convoluted tubule in vivo and in situ. D aspartate and L-phenylalanine (10 mmol/l, each) were added to the perfusate in order keep the reabsorption of L-glutamine as such low and to block reabsorption of any glutamate possibly formed, respectively. Intraluminal formation of glutamate from glutamine in the absence of hippurate is small. In presence of 10 mmol/l hippurate, 5%-70% of the recovered 14C-activity was 14C-glutamate at an initial 14C-L-glutamine concentration of 1 mmol/l. The respective absolute rate (+/- SEM) of glutamate formation, i.e., 36 +/- 5 pmol X s-1 X m-1, was increased 1.4-fold at an initial L-glutamine concentration of 3 mmol/l, but dropped to one third at initially 0.3 mmol/l. A rough estimate of the apparent kinetic constants resulted in a Km of 0.58 (0.19-0.97) mmol/l and a Vmax of 56 (40-93) pmol X s-1 X m-1. Deamidation of glutamine occurred also in the absence of L-phenylalanine. Acivicin (AT 125), a gamma-GT inhibitor, completely blocked glutamate formation. Endogenous hippurate concentrations determined by free flow micropuncture and HPLC were 0.16 mmol/l in the late proximal convolution, 0.6 mmol/l in the early distal convolution, and 4.9 mmol/l in the final urine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881251 TI - RFLP detected at the 8924 locus by a thyroglobulin cDNA probe. PMID- 2881252 TI - A frequent Pvu II RFLP of the human gastrin releasing peptide gene. PMID- 2881253 TI - A RFLP associated with the low-density lipoprotein receptor gene (LDLR). PMID- 2881254 TI - An anonymous genomic clone that detects a frequent RFLP adjacent to the D4S10 (G8) marker and Huntington's disease. PMID- 2881255 TI - RFLPs associated with pMC1, an anonymous single copy clone from the short arm of chromosome 19 [HGM8 assignment no. D19S14]. PMID- 2881256 TI - AvaII polymorphism in the human LDL receptor gene. PMID- 2881257 TI - An Eco R1 polymorphism of a human platelet factor 4 (PF4) gene. PMID- 2881258 TI - BanI dimorphic site in the third intron of the human apolipoprotein AI gene (Apo A1). PMID- 2881259 TI - A high frequency RFLP identified by an anonymous single copy genomic clone at 13q14.1-13q14.2 [HGM8 assignment no. D13S22]. PMID- 2881261 TI - A high-frequency RFLP at the human liver/bone/kidney-type alkaline phosphatase locus. PMID- 2881262 TI - Isolation of an anonymous single copy probe D4S66 (E24) from chromosome 4 associated with a three allele RFLP. PMID- 2881260 TI - Length mutations in human mitochondrial DNA: direct sequencing of enzymatically amplified DNA. AB - A specific segment of mitochondrial DNA from 18 people was examined by two methods of direct DNA sequencing. This segment includes a small noncoding region (V) shown before by restriction analysis to exhibit length polymorphism. All 11 of the human mtDNAs previously reported to have a deletion in this region proved to lack one of the two adjacent copies of a 9-base-pair sequence normally present in human mtDNAs. Phylogenetic analysis suggests that this deletion occurred only once during the evolution of modern types of human mtDNA and that it will be a valuable anthropological marker for peoples of East Asian origin. The one human mtDNA reported to have an addition in region V differs from the wild type by two mutations in the first copy of the 9-base-pair sequence: one transition and an addition of four cytosines, thereby producing a run of 11 cytosines. One of the direct DNA sequencing methods uses a single oligonucleotide primer to facilitate dideoxy sequencing from purified mtDNA templates. The second, more successful, method first amplifies this mtDNA segment enzymatically with two flanking primers (the "polymerase chain reaction") and then uses a third primer for DNA sequencing. This latter method, which works on the DNA extracted from small amounts of blood as well as on purified mtDNA, is shown to be a rapid means of defining sequence variants without purifying and cloning the same DNA segment from many individuals. PMID- 2881263 TI - New RFLPs at the DXS164 (pERT 87-8) locus in the black population. PMID- 2881264 TI - RFLP for the human erb-A1 gene. PMID- 2881265 TI - RFLP for pHM20 (D2S12), an anonymous DNA sequence localised to 2p23-2pter. PMID- 2881266 TI - p380-8A 1.8 SaSs, a single copy clone 5' of c-myc at 8q24 which recognizes an SstI polymorphism. PMID- 2881267 TI - PvuII RFLP inside the human estrogen receptor gene. PMID- 2881269 TI - Isolation of a DNA sequence (lambda EMBL3.123, D4S64) from chromosome 4 showing a BglII polymorphism. PMID- 2881268 TI - Isolation of a polymorphic DNA sequence (lambda EMBL3.303, D2S14) from chromosome 2. PMID- 2881270 TI - RFLP identified by the anonymous DNA segment OL VII A8 at 18q11 (HGM8 no. D18S7). PMID- 2881271 TI - Human apolipoprotein CI (ApoC1) gene locus: BglI dimorphic site. PMID- 2881272 TI - A highly polymorphic locus in 5p15.2-5p15.3 (213-274EC) revealed by an anonymous single copy DNA fragment. PMID- 2881273 TI - A HindIII RFLP for the HPRT pseudogene on chromosome 3 (HPRTP1). PMID- 2881274 TI - Two TaqI RFLPs in the human von Willebrand factor gene. PMID- 2881275 TI - A 5' flanking region of the metallothionein, MT2A, gene identifies two moderately frequent RFLPs. PMID- 2881276 TI - Isolation of polymorphic DNA fragments from human chromosome 4. AB - We have identified and characterized 40 DNA probes detecting restriction fragment length polymorphism (RFLP) on human chromosome 4. Single copy human clones were isolated from a bacteriophage library enriched for chromosome 4 sequences. Each clone was hybridized to somatic cell hybrid DNAs for verification of its species and chromosomal origin and for regional localization. Sequences specific for chromosome 4 were tested for their ability to detect RFLPs in human DNA and their potential utility as genetic markers was assessed. Approximately 263,000 base pairs or 0.13% of the chromosome was screened for sequence variation. The estimate of heterozygosity calculated from this large body of data, H = 0.0021, indicates that the degree of sequence variation on chromosome 4 is comparable to other autosomes. The characterization of these 40 markers has tripled the number of polymorphic loci available for linkage studies on chromosome 4, making it feasible to begin construction of a detailed linkage map that will span the entire chromosome. PMID- 2881278 TI - RFLPs for the human erythrocyte membrane glycophorin C gene. PMID- 2881277 TI - Rat prostatic binding protein: the complete sequence of the C2 gene and its flanking regions. AB - The complete sequence (2879 bp) of the androgen-controlled rat prostatic binding protein C2 gene and 1023 bp of the 5'- and 2127 bp of the 3'-flanking regions have been determined. The gene contains three exons (93, 203 and 147 bp) and two introns (1630 and 806 bp). It is flanked by two homopurine-homopyrimidine stretches of 55 and 131 nucleotides respectively, located at positions -405 and 4151. These sequences are remarkably sensitive towards S1-nuclease, indicating an altered DNA conformation under superhelical stress. Several palindromes and dyad structures are observed in the 5'-upstream region of the gene and at position 457, and 80% homology to the consensus sequence of a glucocorticoid receptor binding site is found. PMID- 2881279 TI - Mouse skeletal alpha actin has limited restriction fragment length polymorphism and is not a member of the human 1q-mouse distal chromosome 1 syntatic group. PMID- 2881280 TI - RFLP detected with a 5'-bcr-gene-sequence (HGM8 provisional no. D22S11). PMID- 2881281 TI - Human apolipoprotein CI (apoC1) gene locus: DraI dimorphic site. PMID- 2881282 TI - [Gamma-glutamyl transpeptidase, lactase and maltase activity in the intestinal mucosa of children with chronic diarrhea]. PMID- 2881284 TI - [Methods of determining gamma-glutamyltransferase]. PMID- 2881283 TI - Pancreatic islets in older patients with cystic fibrosis with and without diabetes mellitus: morphometric and immunocytologic studies. AB - Forty patients with cystic fibrosis (CF), including 34 who died above age 10 years without having developed clinical diabetes mellitus and 6 who died with both cystic fibrosis and diabetes mellitus, were studied. The mean age of the female patients with CF but not diabetes was 15.8 +/- 5.6 years; of males without diabetes, 17.2 +/- 6.4 years; of female patients with CF and diabetes mellitus, 20.2 +/- 6.9 years; and of males with CF and diabetes, 21.3 +/- 6.6 years. The mean number of pancreatic islets in microscopic sections for patients with cystic fibrosis but not diabetes was 4.18 +/- 2.76/mm2, and the value for patients with both cystic fibrosis and diabetes mellitus was 2.61 +/- 2.07/mm2. The lowest density of pancreatic islets (1.69 +/- 0.48/mm2) for cystic fibrosis was found in patients with the latest-stage pathologic lesion. Nesidioblastosis (presence of ductuloinsular complexes) was identified in 14 of 38 cystic fibrosis patients, both with and without diabetes mellitus. The pancreatic islets of both diabetic and nondiabetic patients with CF showed hypertrophy; the mean volume of the three largest pancreatic islets for CF only was 0.0117 +/- 0.00657 mm3 and that for cystic fibrosis and diabetes was 0.00795 +/- 0.00599 mm3, both values being larger than normal. Ratios of the amounts of islet endocrine cells, A cells, B cells, and D cells, were determined by peroxidase--anti-peroxidase labeled antibody staining. The B cells composed 43.0% of endocrine cell mass in cystic fibrosis alone and 30.1% in cystic fibrosis with diabetes mellitus, which were lower than normal proportions. The D cell values, 11.9% in cystic fibrosis and 15.1% in cystic fibrosis with diabetes mellitus, on the other hand, were greater than normal ratios. PMID- 2881285 TI - [APUD cells in the respiratory system of humans and animals: morphologic study]. PMID- 2881286 TI - [Percutaneous transluminal coronary angioplasty in Takayashu's disease]. PMID- 2881287 TI - [Hemorrhagic fever with renal syndrome in central France. Epidemiological data]. PMID- 2881288 TI - [Interactions of thyrotropin and prostaglandins E2 with receptors and their effect on the cAMP levels in human thyroid tissue]. AB - A study was made of the interactions of prostaglandins E2 (PGE2) and TTH with receptors and their effect on the cAMP level using thyroid tissue obtained suboperatively from patients with nodular euthyroid goiter and diffuse toxic goiter. There was no significant difference in the kinetic characteristics of TTH receptor interaction in euthyroid and thyrotoxic thyroid tissue. At the same time in thyrotoxicosis there was a decrease in the pool of free receptors to 3H-PGE2, probably, determined by a rise of the formation of receptor complexes with endogenous PGE2 whose content in thyrotoxic tissue was raised. In thyrotoxic thyroid tissue the PGE2 effect maintained in the presence of a decrease in the stimulating TTH action on the cAMP level. PMID- 2881289 TI - Alpha 2-adrenoceptor antagonists as antidepressants: the search for selectivity. PMID- 2881290 TI - Chronic neuroleptic effects on dopamine neuron activity: a model for predicting therapeutic efficacy and side effects? PMID- 2881291 TI - Effect of neuroleptics on the schizophrenic syndrome. PMID- 2881292 TI - Pharmacokinetic and pharmacodynamic factors causing variability in response to neuroleptic drugs. PMID- 2881293 TI - Correlating pharmacokinetics and pharmacodynamics of benzodiazepines: problems and assumptions. PMID- 2881294 TI - Comparative pharmacodynamics of benzodiazepines. PMID- 2881295 TI - Clinical studies of "specific" anxiolytics as therapeutic agents. PMID- 2881296 TI - Treatment of nitrosamine-induced pancreatic tumors in hamsters with analogs of somatostatin and luteinizing hormone-releasing hormone. AB - Pancreatic ductal adenocarcinoma was induced in female Syrian golden hamsters by injecting N-nitrosobis(2-oxopropyl)amine (BOP) once a week at a dose of 10 mg per kg of body weight for 18 weeks. Hamsters were then treated with somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) or with [6-D tryptophan]luteinizing hormone-releasing hormone [( D-Trp6]LH-RH) delayed delivery systems. Microcapsules of somatostatin analog RC-160, designed to release a dose of 5 micrograms/day, were injected twice a month and microcapsules of [D-Trp6]LH-RH, calculated to liberate 25 micrograms per day, once a month. After 18 weeks of BOP administration, the hamsters were divided into three groups of 10-20 animals each. Group I consisted of untreated controls, group II was injected with RC-160, and group III was injected with [D-Trp6]LH-RH. A striking decrease in tumor weight and volume was obtained in animals treated with [D Trp6]LH-RH or with the somatostatin analog RC-160. After 45 days of treatment with either analog, the survival rate was significantly higher in groups II and III (70%), as compared with the control group (35%). The studies, done by light microscopy, high-resolution microscopy, and electron microscopy, showed a decrease in the total number of cancer cells and changes in the epithelium, connective tissue, and cellular organelles in groups II and III treated with the hypothalamic analogs as compared to controls. These results in female hamsters with induced ductal pancreatic tumors confirm and extend our findings, obtained in male animals with transplanted tumors, that [D-Trp6]LH-RH and somatostatin analogs inhibit the growth of pancreatic cancers. PMID- 2881297 TI - The Thy-1 antigen exhibits rapid lateral diffusion in the plasma membrane of rodent lymphoid cells and fibroblasts. AB - Thy-1 is a plasma membrane protein, but its primary structure lacks the typical membrane-spanning sequence. Recent studies revealed that a glycophospholipid is covalently bound to the carboxyl terminus, suggesting that the protein is integrated into the plasma membrane by this lipid moiety. Lateral diffusion of Thy-1 was measured in mouse thymocytes, lymphoma cells, and fibroblasts by the fluorescence recovery after photobleaching technique. Thy-1 was labeled with rhodamine-conjugated anti-Thy-1 monoclonal antibodies. Diffusion coefficients of 2-4 X 10(-9) cm2/sec were obtained for the antigen-antibody complex in all the cell types. About 50% of the Thy-1 was mobile. The diffusion coefficient for the mobile fraction of Thy-1 is considerably larger than the diffusion coefficients of many other plasma membrane proteins. Rather, the diffusion coefficient of Thy 1 is similar to those of lipid analogs embedded in the same membrane, providing strong support for the suggested lipid anchoring of this antigen. PMID- 2881298 TI - Alpha 2-adrenergic receptor-mediated sensitization of forskolin-stimulated cyclic AMP production. AB - Preincubation of HT29 human colonic adenocarcinoma cells with alpha 2-adrenergic agonists resulted in a 10- to 20-fold increase in forskolin-stimulated cyclic AMP production as compared to cells preincubated without agonist. Similar results were obtained using either a [3H]adenine prelabeling assay or a cyclic AMP radioimmunoassay to measure cyclic AMP levels. This phenomenon, which is termed sensitization, is alpha 2-adrenergic receptor-mediated and rapid in onset and reversal. Yohimbine, an alpha 2-adrenergic receptor-selective antagonist, blocked norepinephrine-induced sensitization, whereas prazosin (alpha 1-adrenergic) and sotalol (beta-adrenergic) did not. The time for half-maximal sensitization was 5 min and the half-time for reversal was 10 min. Only a 2-fold sensitization of cyclic AMP production stimulated by vasoactive intestinal peptide was observed, indicating that sensitization is relatively selective for forskolin. Sensitization reflects an increased production of cyclic AMP and not a decreased degradation of cyclic AMP, since incubation with a phosphodiesterase inhibitor and forskolin did not mimic sensitization. Increasing the levels of cyclic AMP during the preincubation (using a phosphodiesterase inhibitor) had no effect on sensitization, indicating that sensitization is not caused by decreased cyclic AMP levels during the preincubation. This rapid and dramatic sensitization of forskolin-stimulated cyclic AMP production is a previously unreported effect that can be added to the growing list of alpha 2-adrenergic responses that are not mediated by a decrease in cyclic AMP. PMID- 2881299 TI - The yeast PHO5 promoter: phosphate-control elements and sequences mediating mRNA start-site selection. AB - Transcription of PHO5 is strongly regulated in response to the level of inorganic phosphate (Pi) present in the growth medium. We have identified elements required for PHO5 expression by analyzing small deletions in the PHO5 promoter on chromosome II. The results reveal three functionally different components of the PHO5 promoter: regulatory regions, a "TATA" element, and specific mRNA initiation sites. The regulatory regions contain related 19-base-pair (bp) dyad sequences acting as phosphate-controlled upstream activation sites (UASpS). These UASpS mediate the transcriptional activation of PHO5 observed in low Pi conditions. The unlinked but coordinately regulated PHO11 promoter contains a single copy of an almost identical dyad sequence, suggesting that there is a common regulatory UASp for both genes. A TATA element is absolutely required for detectable PHO5 transcription. Specific purine-pyrimidine motifs (RRYRR) (R = purine and Y = pyrimidine) serve as PHO5 mRNA initiation sites, but only if they lie 55-110 bp downstream of a functional TATA element. Such an "initiation window" is not found in higher eukaryotes and implies mechanistic differences in the transcription machineries between yeast and higher eukaryotes. PMID- 2881300 TI - Immunochemical studies of fibroblasts from patients with methylmalonyl-CoA mutase apoenzyme deficiency: detection of a mutation interfering with mitochondrial import. AB - Methylmalonyl-CoA mutase (2-methylmalonyl-CoA CoA-carbonylmutase, EC 5.4.99.2) is a mitochondrial enzyme whose deficiency in man leads to several biochemically and clinically heterogenous++ forms of methylmalonic acidemia. Intact fibroblasts from 21 patients with mutase apoenzyme deficiency have been pulse-labeled with [3H]leucine or [35S]methionine to determine how amounts of newly synthesized mutase recovered from these cells by immunoprecipitation compare with the amounts of steady-state crossreacting material previously determined. Ten lines (3 mut-, 7 mut 0 ), previously shown to have detectable steady-state crossreacting material, had amounts of newly synthesized mutase that varied from similar (7 lines) to considerably greater than (3 lines) the steady-state amounts. Of 11 lines that had no detectable steady-state crossreacting material, 6 had no detectable newly synthesized mutase, and 5 had amounts of mutase ranging from just detectable to almost half that of control. This result suggests that, at least for this latter group, one effect of the mutation in the mutase gene is to reduce the stability of the mutase protein. We examined fibroblasts from 48 patients with mutase apoenzyme deficiency to determine the sizes of the mature mutase subunit and the mutase precursor accumulated in the presence of the mitochondrial transport inhibitor rhodamine 6G. Of the 38 lines that had detectable newly synthesized mutase, only 2, lines 437 and 552, showed a pattern different from that generated by the normal precursor and mature subunits. Line 437 had two immunoprecipitable precursor proteins in the presence of rhodamine, each of which appeared to be transported and processed in the cells to produce two distinct mature proteins. Line 552 also had two anti-mutase reactive proteins in the presence of rhodamine, but each was smaller than the normal mature subunit and neither appeared to be proteolytically processed. The defect in line 552 is almost certainly an amino-terminal deletion that removes the leader peptide necessary for proper uptake and cleavage of the mutase precursor; this represents a clear example of a natural human mutation that interferes with mitochondrial transport of a protein. PMID- 2881301 TI - Foot-and-mouth disease--one of the remaining great plagues. PMID- 2881303 TI - End-stopped cells and binocular depth discrimination in the striate cortex of cats. AB - Proposals concerning neural mechanisms for binocular depth discrimination have been criticized on the grounds that only striate cells with a preferred stimulus orientation not too far from the vertical can make significant horizontal disparity discriminations. We investigated this claim by preparing a two dimensional array of position-disparity response profiles to moving light and dark bars from each of 18 cells in the simple family. From these arrays, it was possible to reconstruct disparity response profiles along any axis across the receptive field, irrespective of the cell's optimal stimulus orientation. This analysis showed that cells with a predominantly excitatory binocular response (N = 10) can make precise horizontal disparity discriminations, independent of their optimal stimulus orientation, provided that they are sufficiently end stopped. End-free cells, on the other hand, are effective for horizontal disparity discriminations only if their preferred orientation are near the vertical. Nearly all striate cells we examined were end-stopped to some degree and nearly half had an end inhibition sufficient to reduce the monocular response from the dominant eye to half its maximal amplitude. Cells having a predominantly inhibitory disparity response profile of the symmetric type (N = 8) have an inhibitory profile along every axis across the receptive field. An outline is given of a neural mechanism for the determination of absolute viewing distance based on the sensitivities of striate cells to vertical retinal-image disparities. PMID- 2881302 TI - Stereoscopic mechanisms: binocular responses of the striate cells of cats to moving light and dark bars. AB - New knowledge concerning the internal structure and response properties of the receptive fields of striate cells calls for a fresh appraisal of their binocular interactions in the interest of a better understanding of the neural mechanisms underlying binocular depth discrimination. Binocular position-disparity response profiles were recorded from 71 simple and B-cells in response to moving light and dark bars. Predominantly excitatory (PE) cells (N = 48) had disparity response profiles that were spatially closely similar to their respective monocular responses. In addition, the centrally located excitatory subregions were flanked on one or both sides by non-specific inhibitory regions. PE cells with a preferred stimulus orientation within 30 degrees of the vertical (N = 17) showed binocular facilitations with maximal values that were always more than twice (mean 3.3) the sum of the two monocular responses to the same stimuli and generally greater than the facilitations shown by cells with orientations more than 30 degrees from the vertical (N = 29; mean 2.2 times the sum of the respective monocular responses). The strength of the binocular facilitation depended on the stimulus contrast, the facilitation decreasing with increasing contrast. The receptive-field disparity distribution of the 31 PE cells capable of making significant horizontal disparity discriminations has standard deviations of 0.37 degrees and 0.40 degrees, respectively. Predominantly inhibitory cells (PI) (N = 23) showed two basic types of disparity response profile: symmetric (N = 17) and asymmetric (N = 6). Uncertainty regarding the precise location of the binocular fixation point in the anaesthetized and paralysed preparation made it difficult to categorize PI cells adequately. PMID- 2881304 TI - Factors responsible for a karyotypic polymorphism in the common shrew, Sorex araneus. AB - A Robertsonian karyotypic polymorphism in the common shrew in the Oxford area, first described in the 1950s, was re-examined. The polymorphism involves chromosome arm combinations kq, no and pr (characteristic of the Oxford karyotypic race), ko (characteristic of the Hermitage karyotypic race) and jl (found in both races). The polymorphism for jl was sporadic along a north-south transect through the Oxford area, with the frequency of the twin-acrocentric morph never exceeding 10%. The frequency of the Oxford race-specific metacentrics decreased and the frequency of the Hermitage race-specific metacentric ko increased from north to south along the transect. At a latitudinal grid reference of about 180 km, there was a high frequency of individuals with chromosome arms k, n, o and q in the ancestral acrocentric state. This was coincident with the area of occurrence of ko-kq and ko-no Oxford-Hermitage hybrids. Such hybrids are double Robertsonian heterozygotes with monobrachial homology and are likely to suffer reduced fertility in consequence. It is proposed that this is a source of selection against the monobrachial hybrids and hence results in an increase in frequency of the acrocentric morphs. This scheme goes some way to explain the clines of polymorphism for arm combinations kq, no and ko, but it is suggested that other selective factors are involved. It cannot explain the cline of polymorphism for pr, which is in general terms similar to that for kq and no, but is more shallow and centred further north. PMID- 2881305 TI - Measures of cooperativity in the binding of ligands to proteins and their relation to non-additivity in protein-protein interactions. AB - The analogy between cooperativity in the binding of ligands to proteins and non additivity in protein-protein interactions is demonstrated and discussed in terms of the Wong and the Hill coefficients. A measure of non-additivity, the interaction constant, is rigorously derived for four thermodynamic cycles, involving the binding of small molecules to proteins and protein association. It is the reciprocal of the 'defect factor' of Laskowski et al. in Proteinase inhibitors: medical and biological aspects (ed. N. Katunuma et al.), pp. 55-68 (1983), and its logarithm is the Wong measure of cooperativity. These three measures are thus here given a common theoretical basis. The Hill coefficient for an asymmetric dimer that binds two different ligands which do not compete for the same site, at 50% saturation of each site, is derived. It is shown to be a function of the interaction constant and of the fraction of protein to which ligand is bound at both sites. These relations for protein-ligand interactions are then discussed in the context of non-additivity in protein-protein interactions. PMID- 2881307 TI - A model to account for the elastic element in muscle crossbridges in terms of a bending myosin rod. AB - We advance a structural model to account for the rapid elastic element seen in mechanical transient experiments on vertebrate skeletal muscle (A.F. Huxley & Simmons 1971 Nature, Lond. 233, 533-538). In contrast to other crossbridge models, ours does not envisage a myosin rod made up of two rigid portions connected by a hinge, but rather a gradually bending rod portion connecting the heads to the thick filament shaft. We propose that, in relaxed muscle, the subfragment 2 (S2) portion of the myosin rod is bound to the thick filament shaft by ionic interactions analogous to those between the light meromyosin (LMM) portions of the rod that constitute the body of the shaft. These interactions probably involve the alternating zones of positive and negative charge seen in myosin rod amino acid sequences. As the crossbridge cycle that generates tension begins, we propose that part of S2 detaches from the thick filament shaft and bends to enable the myosin head to attach to actin. When tension develops in the crossbridge, the S2 is straightened and more of it becomes detached from the shaft so that the junction between S2 and the myosin heads moves 3-4 nm axially. As tension declines at the end of the crossbridge stroke, we propose that S2 rebinds to the thick filament shaft and that this provides the restoring force to return the junction of the heads and S2 to its original axial position. Thus this movement would have the characteristics of an elastic element; detailed calculations indicate that it would have properties similar to those observed experimentally. Furthermore, this model can account for the radial attractive force seen in rigor and in contracting muscle, the decrease in stiffness when interfilament spacing is increased in skinned muscle, and the increased rate of proteolysis observed at the S2-LMM junction in contracting muscle. PMID- 2881306 TI - Cone connections of the horizontal cells of the rhesus monkey's retina. AB - The presence in the rhesus monkey's retina of a second morphological type of horizontal cell (H2), described by Kolb et al. (1980), is confirmed. Both types of cell are here further described. Their cone connections are quantified and compared with those of mammals and other vertebrates. The dendrites and axons of the H2 type of cell contact only cones as do the dendrites of the H1 cell (originally described by Polyak (1941)) which has an axon contacting only rods. The dendrites of foveal H2 cells contact between 11 and 14 cones; those of H1 contact 7. The number of cones that each type of cell contacts increases with increasing distance from the fovea, so that, by 5-6 mm eccentricity, H2-type cells synapse with between 20 and 30 cones, and the H1 cells with 12-15. The qualitatively estimated coverage factors of each are 3 or 4; every cone synapses with more than one of both types. Neither type of horizontal cell makes chromatically specific connections that are anatomically recognizable, unlike the situation in some teleostean and turtle retinae. Individual horizontal cells, particularly those connected to foveal cones, may have different ratios of chromatic input. At equivalent eccentricities, up to about 6 mm from the fovea, the dendritic fields of H2 horizontal cells are about twice the size of H1 cells and contact about twice the number of cones. These relative differences are closely similar to those of the cat's horizontal cells and it is suggested that they are a basic feature of most placental mammals. The organization of foveal cone fibres within Henle's layer is described. The distribution of primate cone telodendria, gap junctions and synapses in the outer plexiform layer are briefly reviewed and compared with those of other vertebrate retinae. PMID- 2881308 TI - Vision of the Humboldt penguin (Spheniscus humboldti) in air and water. AB - Refractive states measured by retinoscopy and photorefraction indicate that the eyes of the Humboldt penguin, Spheniscus humboldti, are approximately emmetropic in air and water. Extensive myopia in air, as predicted by earlier authors and by a recent anatomical study, is non-existent. Photorefractive measurements of the refractive state, in water, of the Humboldt penguin indicate that it can accommodate sufficiently to make up the loss of the refractive power of the cornea. The cornea of the Humboldt penguin is flattened relative to the overall size of the eye. In all these respects (corneal flattening, and accommodation in air and water) the eyes of Humboldt penguins are like those of gentoo, (Pygoscelis papua), rockhopper (Eudyptes crestatus), Magellanic (Spheniscus magellanicus), and king penguins (Aptenodytes patagonica). PMID- 2881309 TI - Quipazine-metoclopramide inhibition of CB-154-induced prolactin suppression in rats: neurotransmitter-metabolite correlations. AB - The ability of quipazine and metoclopramide to protect rats from CB-154-induced suppression of serum prolactin concentrations was studied. These drugs affect whole brain concentrations of dopamine and serotonin, and their major metabolites dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid. Serum prolactin concentrations have been correlated with the concentrations of the neurotransmitters and their respective metabolites. Differences in the metabolite/precursor ratios have been used to compare turnover rates of the neurotransmitters dopamine and serotonin. Increased turnover of dopamine and decreased turnover of serotonin correlate with elevated prolactin concentrations for quipazine and metoclopramide administered together. The combination of quipazine and metoclopramide protects rats against CB-154-induced prolactin suppression better than either of the drugs given alone. This study suggests that a quipazine-metoclopramide regimen may have therapeutic potential for combating ergotlike fescue and other similar toxicities observed in cattle grazing on endophyte-infected pasture grasses. PMID- 2881310 TI - The effects of gastrin, epidermal growth factor, and somatostatin on DNA synthesis in a small intestinal crypt cell line (IEC-6). AB - Exposure of IEC-6 cells for 24 hr to either gastrin (50-500 ng/ml) or EGF (100 500 ng/ml) significantly stimulated (100-165%) the rate of [3H]thymidine incorporation into DNA (referred to as DNA synthesis) when compared with the corresponding basal levels. Somatostatin (10-500 ng/ml) produced no apparent change in DNA synthesis in IEC cells. On the other hand, somatostatin completely inhibited the EGF-induced rise in DNA synthesis. The gastrin-mediated stimulation in DNA synthesis was not affected by somatostatin. The rate of DNA synthesis in IEC cells in the presence of both gastrin and EGF was found to be greater (additive) than that caused by either of the peptides alone. A similar but less dramatic change in the actual number of cells (assessment of cell replication) was observed when the IEC cells were exposed for 24 hr to gastrin, EGF, and somatostatin, either alone or in combination. Whereas gastrin (250 ng/ml) and EGF (250 ng/ml) by themselves increased the number of cells significantly by 29 and 37%, respectively, together they caused a 72% stimulation, when compared with the basal levels. Somatostatin by itself caused no apparent change in IEC cell population, but it significantly inhibited the EGF- but not the gastrin-induced stimulation in IEC cell replication. It is concluded that both gastrin and EGF exert a direct proliferative effect on IEC cells, and the EGF action is regulated by somatostatin. PMID- 2881311 TI - Cephalic sensory pathways in the central nervous system of larval Manduca sexta (Lepidoptera : Sphingidae). AB - Central projections of neurons innervating sensory structures on the head of larval Manduca sexta were traced by using methods of anterograde cobalt diffusion. Regions of the deutocerebrum and tritocerebrum in the brain receive input from the antenna, labrum, maxilla, labial palps, hypopharynx and other unidentified regions of the buccal cavity. Antennal, maxillary and labial inputs project to the larval antennal centre (LAC) of the deutocerebrum. Stemmatal neurons and a few antennal neurons project into the protocerebrum. The suboesophageal ganglion (SEG) receives input from mechanosensory neurons in all parts of the head and its sensory appendages. Some mechanosensory neurons project further to the first thoracic ganglion. In addition to receiving input from chemosensory neurons of the maxilla, the SEG may also receive chemosensory input from epipharyngeal sensilla of the labrum. PMID- 2881312 TI - [A conversation with Grazyna Jankowska. Interview by Krystyna Serafin]. PMID- 2881313 TI - Psychotropic drug use in Italy: national trends and regional differences. AB - Psychotropic drug sales data for Italy were examined for the years 1975-84. The principal findings were of more-or-less consistent annual increases in sales of antidepressants, minor tranquillizers and, to a lesser extent, of neuroleptics. These trends are interpreted in the context of the characteristics of the Italian National Health Service (NHS), and in relation to findings from psychotropic drug utilization studies in other Western countries. Regional differences in psychotropic drug sales for 1983/4 were also examined. Marked differences were found and, in general, levels of use were higher in North/Central Italy than in the South. Factors influencing regional differences were explored using regression analysis. Regional NHS expenditure (excluding that on drugs) was found to influence strongly the sales of all categories of psychotropic drug, whereas there was also a marked urban greater than rural difference in the sales of tranquillizers. PMID- 2881314 TI - Naloxone blocks the effects of chlordiazepoxide on acquisition but not performance of differential reinforcement of low rates of response (DRL). AB - The opiate antagonist naloxone can completely or partially reverse the effects of the benzodiazepines on appetitive behaviours and conflict tasks involving electric shook. If naloxone changes the anxiolytic action of the benzodiazepines it should theoretically, be effective in tasks employing nonreward as well as those employing shock. We tested naloxone and chlordiazepoxide on acquisition and performance of a nonreward task, DRL. With both continuous administration during acquisition of DRL, and intermittent administration during stable performance, chlordiazepoxide (5 mg/kg IP) increased burst responding and shifted the peak of the inter-response time (IRT) distribution curve to shorter IRTs. Naloxone (3 mg/kg IP) blocked the effects of chlordiazepoxide on acquisition of DRL. Naloxone (3 mg/kg and 10 mg/kg IP) did not change the effects of chlordiazepoxide on well learned performance of the DRL schedule. These results show that endogenous opiates could mediate some but not all of the actions of the benzodiazepines. They also suggest that state-dependent and "truly anxiolytic" effects of the benzodiazepines (McNaughton 1985) may have different pharmacological substrates. PMID- 2881315 TI - Naloxone fails to block the effects of chlordiazepoxide on acquisition and performance of successive discrimination. AB - Naloxone reduces the effects of chlordiazepoxide on punishment and on acquisition of differential reinforcement of low rates of response. The present experiments tested whether naloxone also reduces the effects of chlordiazepoxide on a second type of nonreward schedule--successive discrimination. Rats were tested on a variable interval baseline of responding for food with signalled intrusion periods when food was no longer available. Naloxone (3 mg/kg IP) failed to change the effects of chlordiazepoxide (5 mg/kg IP) on either acquisition or performance of this successive discrimination. DRL and successive discrimination differ both in their timing of events and their use of explicit visual stimuli. If these or similar parametric differences account for the present results they considerably weaken conventional accounts of the control of behaviour by reward omission. PMID- 2881317 TI - The status of late-onset vacuous chewing/perioral movements during long-term neuroleptic treatment in rodents: tardive dyskinesia or dystonia? PMID- 2881316 TI - Transient supression by stress of haloperidol induced catalepsy by the activation of the adrenal medulla. AB - Rats were injected with haloperidol (0.5-1.0 mg X kg-1). When the catalepsy score was almost maximal (60 s, measured by the bar-test), the rats were handled, exposed to cold (3 degrees C) or immobilized. After each of these stress procedures the catalepsy was significantly reduced. Handling of adrenalectomized rats gave no such reduction. Infusion of adrenaline (10 nmol X kg-1, given in 15 s), in contrast to that of isoprenaline and phenylephrine (both the same concentration as adrenaline) also reduced the haloperidol induced catalepsy. These findings indicate that neuroleptic catalepsy in rats is not only mediated through central but also through peripheral mechanisms, e.g. by the adrenal medulla. PMID- 2881318 TI - The interoceptive discriminative stimuli induced by the novel putative anxiolytic TVX Q 7821: behavioral evidence for the specific involvement of serotonin 5-HT1A receptors. AB - TVX Q 7821 is active in several behavioral models of anxiety in animals and has a high selective affinity for brain serotonin 5-HT1A receptors in binding assays. In order to determine if interaction with 5-HT1A receptors is important for some of the behavioral effects of this compound, 11 rats were trained to reliably discriminate the interoceptive stimuli induced by TVX Q 7821 (10 mg/kg, IP) from those of saline. Following discrimination acquisition, TVX Q 7821 administration resulted in drug-appropriate responding with an ED50 of 1.5 mg/kg, as did other substances with high affinity for the 5-HT1A receptor: 8-hydroxy-2-(di-n propylamino)-tetralin (8-OH-DPAT, ED50 = 0.16 mg/kg), 5-methoxy-N,N dimethyltryptamine (5-OMe-DMT, ED50 = 2.5 mg/kg), and buspirone (ED50 = 5.4 mg/kg). Anxiolytics not acting via the 5-HT1A receptor, like diazepam and pentobarbital, did not induce full TVX Q 7821-appropriate responses. In addition, non-selective 5-HT agonists and antagonists such as bufotenin, quipazine, and methysergide, as well as substances with high affinity for the 5-HT1B receptor (m trifluoromethylphenylpiperazine, TFMPP; 5-methoxy-3(1,2,3,6-tetrahydropyridin-4 yl)-1H-indole succinate, RU 24969) did not substitute for TVX Q 7821. These data support a selective 5-HT1A mechanism of action in vivo for TVX Q 7821 and indicate the suitability of TVX Q 7821 for the investigation of behavioral correlates of the 5-HT1A receptor. PMID- 2881319 TI - Haloperidol-induced emotional defecation: a possible model for neuroleptic anxiety syndrome. AB - The neuroleptic haloperidol was found to produce increased defecation in laboratory rats when tested in well habituated environments. It is well known that haloperidol induces catalepsy through antagonism of striatal dopaminergic receptor mechanisms. When another cataleptic agent, morphine, was tested, no significant increases in defectation were detected. Another study focused on the possible role of peripheral dopamine receptor sites within the gastrointestinal tract on neuroleptic-induced defecation. When the peripheral dopamine receptor antagonist domperidone was tested, no significant differences in fecal elimination were recorded. Thus, it appeared that the cataleptic state per se, or the peripheral effects of haloperidol did not seem to be responsible for the increased defecation. Defection is often used as an index of emotionality. The fact that this measure increased following administration of a major tranquilizer suggested the need to study more directly the relationship of this phenomenon of defecation with the affective state of the animal. In a control study it was found that the antianxiety agent benzodiazepam did not by itself influence defecation. However, those animals which were pre-injected with diazepam followed by haloperidol did not show increased defecation. Thus under certain circumstances, normal rats given haloperidol show "emotional defecation" which seems to reflect increased anxiety. This finding may serve as a basis for the development of an animal model for some of the atypical side effects of major tranquilizers, such as akathisia, dysphoria, and neuroleptic anxiety syndrome. PMID- 2881320 TI - Double blind controlled trials of cholecystokinin octapeptide in neuroleptic refractory schizophrenia. AB - A group of 14 schizophrenics who remained symptomatic after neuroleptic treatment received either 0.02 mcg/kg CCK-8 or saline placebo intravenously. Thereafter, 13 received the alternative infusion as a crossover treatment. A second group of 16 such patients received 0.04 mcg/kg CCK-8 or saline intravenously and, thereafter, 14 of these received the alternative infusion as a crossover treatment. Psychopathology was rated prior to, 2-3 h post, and on days 3, 5 and 7 after each infusion. Ratings consisted of the BPRS, the Abrams and Taylor Scale for Emotional Blunting, the Hamilton Anxiety Scale and a Schneiderian "Positive" symptom scale abstracted from the President State Examination. Parallel groups and cross over design analyses failed to show efficacy for CCK-8. PMID- 2881321 TI - [Ammonia content of the brain, liver and blood of rats in radiation injury]. AB - The neuroparalytic syndrome induced by ammonia was compared with the X-radiation induced cerebral syndrome. It is suggested that the accumulation of ammonia in the brain and liver of rats is one of the reasons for the similarity of the studied syndromes. The fact that ammonia is bound by glutamic acid indicates that the latter is involved in the mechanisms of ammonia utilization and in the radioprotective properties manifestation. PMID- 2881322 TI - Current management of inflammatory bowel disease. AB - Since the etiology and cure for inflammatory bowel disease remain elusive, treatment is still largely empiric. The major goals of therapy include control of bowel inflammation and alleviation of symptoms. Careful attention must be directed toward special problems when appropriate, such as short bowel syndrome, perianal disease, extraintestinal disease manifestations, and cancer surveillance. Standard and new forms of medical therapy and the approach to special problems will be discussed. PMID- 2881323 TI - Pharmacological aspects of visceral sensory receptors. PMID- 2881324 TI - Transmitter circuits in the vertebrate retina. PMID- 2881326 TI - Pharmacology and biochemistry of neurotensin receptors. PMID- 2881325 TI - Treatment of duodenal ulcer. AB - Although gastric acidity is essential for the development of DU, the pathogenesis is more complex and includes an imbalance in the "defending" forces, mainly in mucous secretion, prostaglandin and bicarbonate synthesis and cell turnover. The new drugs available for inhibition of acid secretion, ulcer isolation and cytoprotection make it possible to attack the problem from different sites. The decision of which drug to choose should take into account side effects, drug interactions, cost and recurrence. PMID- 2881327 TI - Proceedings of the 1985 annual meeting of the Israeli Physiological and Pharmacological Society. PMID- 2881328 TI - Phorbol ester enhances calcium influx, protein phosphorylation and neurotransmitter release in cultured brain neurons. PMID- 2881329 TI - [Sale of drugs without medical prescription in pharmacies of the city of Sao Paulo]. PMID- 2881330 TI - [Comparative study between vecuronium bromide and pancuronium]. PMID- 2881331 TI - [Controversies over the staged treatment of essential arterial hypertension]. PMID- 2881332 TI - [Current problems in the treatment of gastroduodenal ulcer]. PMID- 2881333 TI - [Current developments in the treatment of chronic glomerulonephritis]. PMID- 2881334 TI - [Etiology of viral respiratory infections in adults. Clinical considerations and therapeutic directions. A study of 100 cases]. PMID- 2881335 TI - [The risk of chronicity in acute viral hepatitis. A study of 1614 convalescents followed for a year after hospitalization]. PMID- 2881336 TI - [Sensitivity and resistance to dietary salt restriction in patients with essential arterial hypertension]. PMID- 2881337 TI - [Immunomodulatory effect of Freund's incomplete adjuvant in patients with incipient forms of rheumatoid polyarthritis]. PMID- 2881338 TI - [Treatment of schizophrenia with powerful neuroleptics]. PMID- 2881339 TI - [Neuro-immunology. A new branch of neurology]. PMID- 2881340 TI - Structural and functional studies of Gilles de la Tourette syndrome. AB - Preliminary studies with PET-scanner and nuclear magnetic resonnance have shown no abnormalities in Gilles de la Tourette syndrome. Estimation of homovanillic acid, the main metabolic of dopamine, in the cerebrospinal fluid of patients with Gilles de la Tourette disease suggests that brain dopaminergic receptors are hypersensitive. Such an hypersensitivity of dopamine receptors is in agreement with the clinical improvement of patients treated with neuroleptic drugs. The study with PET-scanner presented here suggests the existence of a neuronal hypofunction in some striatal and corticolimbic area in patients. PMID- 2881341 TI - Neuropharmacology of tics. AB - In pharmacological treatment of Gilles de la Tourette's syndrome neuroleptic (antipsychotic) drugs have been the most effective. This has led to the hypothesis of a relative dopaminergic overactivity in the brain. Animal studies with neuroleptic drugs different in their affinity to different dopamine areas as well as studies with drugs different in their selectivity to different receptors have, however, not shown direct correlations to the clinical response in the treatment of hyperkinetic syndromes. There is a trend that drugs with high affinity to striatal D2-receptors might be the most potent. Other attempts to change brain dopamine in different ways using cholinergic, GABAergic, and peptidergic drugs have given rather poor clinical results. The apparent importance of brain dopamine in a whole range of neuropsychiatric diseases may be due to the central role of basal dopaminergic areas as a relay station for a lot of neuronal pathways. PMID- 2881342 TI - [The 3% potassium hydroxide test, an alternative to gram staining. II]. PMID- 2881343 TI - Morphine: the benefits are worth the risks. PMID- 2881344 TI - Mechanisms of action of antisecretory drugs. Studies on isolated canine fundic mucosal cells. AB - Cellular mechanisms underlying the actions of antisecretory agents were studied with dispersed canine fundic cells; aminopyrine accumulation monitored parietal cell (PC) function. Canine PC have pharmacologically typical histamine (H) H2 and muscarinic (M) receptors. PC also have gastrin (G) receptors, which were selectively blocked by gastrin/CCK antagonists. Potentiating interactions occurred between secretagogues, one of the components of the interdependency between regulatory pathways. Prostaglandins (PG) E2 inhibited H-stimulated PC function. Treatment of PC with pertussis toxin (PT), which inactivates the inhibitory GTP-binding protein of adenylate cyclase (Gi), markedly reduced PG inhibition, indicating PG action via Gi. PC function can also be directly inhibited by H+/K+-ATPase inhibitors, such as omeprazole. When canine mucosal cells were studied, stimulatory G and inhibitory M receptors were present on fundic somatostatin (S) cells. Histamine was localized to canine fundic mast cells, which lacked G or M receptors, a conclusion that may not pertain to fundic histamine cells in other species. Nonparietal cell receptors may be important modulators of the regulation of acid secretion. PMID- 2881345 TI - Future opportunities for drug therapy in peptic ulcer disease. AB - Attempts to develop antisecretory agents showing a significant increase in potency and duration of action over currently available H2 antagonists have had to contend with the problem of gastric tumour induction during long-term toxicity testing in rats, and their clinical future is currently uncertain. A number of potential pharmacological approaches to ulcer therapy, unrelated to inhibition of acid secretion, can be identified upon which to base the search for new antiulcer drugs. Whether such agents are a commercially attractive proposition is debatable, given the disappointing early clinical experience with prostaglandins in acute healing studies together with the established efficacy and safety of cimetidine and ranitidine. Indeed it is difficult to foresee any agent challenging the dominance of H2 blockers during this century. By analogy with beta adrenoceptor antagonists, it is likely that new developments will take the form of some additions to the H2 range, improved formulations, additional indications, and possibly combination therapies with other drugs. Future research must address the different aetiologies of gastric and duodenal ulcer and other acid-peptic conditions as well as attempting to cure the disease rather than simply heal the ulcer. Advances in fields traditionally unrelated to peptic ulcer research such as growth regulation, vascular disorders, and inflammation may well provide the most profitable basis for longer-term drug research. Finally, animal toxicity studies with second generation antisecretory agents have inadvertently focused attention on gastric cancer, a disease where the need for new drugs is unquestionable. PMID- 2881346 TI - Clinical perspectives of drugs inhibiting acid secretion: histamine H2 antagonists. AB - The present report shows that the following statement is correct: 'Uncomplicated peptic ulcer is best treated with a strongly acting histamine antagonist given once daily with dinner for 4 weeks and by abstention from smoking'. PMID- 2881347 TI - Present status and future perspectives of muscarinic receptor antagonists. AB - Conventional anticholinergics (better called muscarinic antagonists) do not differentiate between subtypes of muscarinic receptors and cause unpleasant side effects in peptic ulcer treatment. Pirenzepine, the first M1-receptor antagonist, has more selective inhibitory properties on oxyntic gastric glands and accelerates healing rates in peptic ulcer. Pirenzepine and H2-receptor antagonists interact synergistically on parietal cell function; their combination seems to be of therapeutic advantage in defined indications. Telenzepine, a pirenzepine analogue with a modified tricycle and M1-receptor selectivity, is about 10 to 25 times more potent than pirenzepine in reducing basal and stimulated gastric acid secretion in man. In patients with duodenal ulcer 3 mg telenzepine nocte seems to be as effective as 50 mg pirenzepine twice daily in regard to ulcer healing and pain relief. Another pirenzepine analogue with a modified side-chain (AF-DX 116) proved to be cardioselective in animal pharmacology, and was characterized as an M2-receptor antagonist. This might be an important step for a more profound understanding of structure-activity relationships of muscarinic receptor antagonists. PMID- 2881348 TI - Effect of acid inhibition on the growth of parietal cells. AB - Studies in the rat have shown that prolonged inhibition of acid secretion by high doses of a histamine H2 antagonist is followed by a 20-30% increase in the number of parietal cells, and that this is paralleled by an augmentation of the maximum acid output. A similar effect has been shown after prolonged acid neutralization with high doses of an antacid. These trophic effects are not unexpected. An increase in gastric pH is followed by gastrin release, and the parietal cell mass may be augmented by repeated exogenous administration of gastrin or by endogenous hypergastrinaemia following surgery. To further evaluate whether a direct correlation exists between the magnitude of drug-induced hypergastrinaemia and parietal cell hyperplasia, rats were treated for 24 days with two acid inhibitors which differ markedly in the degree of acid inhibition and acute or chronic gastrin release. Six animals each were treated with either omeprazole (40 mumol/kg once daily), or atropine (3 mg/kg twice daily), or omeprazole combined with atropine or with placebo. On day 24, plasma gastrin was elevated more than 10-fold in both groups of rats treated with omeprazole but not in animals given atropine alone. As compared to placebo treatment, total parietal cell volume was significantly higher in animals treated with atropine (102 +/- 9 mm3 versus 140 +/- 18 mm3), but was unchanged in the other two groups. These studies demonstrate that marked prolonged drug-induced hypergastrinaemia does not necessarily exert trophic effects on parietal cells. Furthermore, the finding that omeprazole abolishes the effect of atropine suggests that omeprazole interferes with trophic actions on parietal cells. PMID- 2881349 TI - The functional architecture of the retina. PMID- 2881350 TI - Arginine vasopressin as a thyrotropin-releasing hormone. AB - Although hypothyroidism (with concomitant increased levels of thyroid-stimulating hormone) has been associated with elevated plasma vasopressin, the role that vasopressin plays in controlling thyroid-stimulating hormone secretion from the adenohypophysis is not understood. In two in vitro pituitary cell systems, vasopressin caused a specific and dose-related release of thyroid-stimulating hormone from cells that was equal in potency to that elicited by thyrotropin releasing hormone, the primary acknowledged regulator of thyroid-stimulating hormone release. When injected into the hypothalamus, however, vasopressin specifically inhibited the release of thyroid-stimulating hormone. Thus, vasopressin may exert differential regulatory effects on thyroid-stimulating hormone secretion in the hypothalamus and pituitary gland. PMID- 2881351 TI - Polyphosphoinositide research updated. PMID- 2881352 TI - Coexistence of guanylate cyclase and atrial natriuretic factor receptor in a 180 kD protein. AB - Atrial natriuretic factor (ANF) is a peptide hormone that is released from atria and regulates a number of physiological processes, including steroidogenesis in adrenal cortex and testes. The parallel stimulation of membrane guanylate cyclase and corticosterone production in isolated fasciculata cells of rat adrenal cortex has supported the hypothesis of a mediatory role for cyclic guanosine monophosphate (cyclic GMP) in signal transduction. A novel particulate guanylate cyclase tightly coupled with ANF receptor was purified approximately 273,000-fold by two-step affinity chromatography. The enzyme had a molecular size of 180 kilodaltons and was acidic in nature with a pI of 4.7. Its specific activity was 1800 nanomoles of cyclic GMP formed per minute per milligram of protein. The purified enzyme bound ANF with a specific binding activity of 4.01 nanomoles per milligram of protein, a value that is close to the theoretical binding activity of 5.55 nanomoles per milligram of protein for 1 mole of the ligand binding 1 mole of the receptor protein. These results indicate that the guanylate cyclase coupled ANF receptor exists in a 180-kilodalton protein of rat adrenocortical carcinoma and represent a step toward the elucidation of the basic mechanism of cyclic GMP-mediated transmembrane signal transduction in response to a hormone. PMID- 2881353 TI - Region-specific expression of two mouse homeo box genes. AB - Mammalian homeo box genes have been identified on the basis of sequence homology to Drosophila homeotic and segmentation genes. These studies examine the distribution of transcripts from two mouse homeo box genes, Hox-2.1 and Hox-3.1, throughout the latter third of prenatal development. Transcripts from these genes are regionally localized along the rostro-caudal axis of the developing central nervous system, yielding expression patterns very similar to patterns of Drosophila homeotic gene expression. PMID- 2881355 TI - NIMH finds a case of "serious misconduct". PMID- 2881354 TI - F-actin and microtubule suspensions as indeterminate fluids. AB - The viscosity of F-actin and microtubule suspensions has been measured as a function of shear rate with a Weissenberg rheogoniometer. At shear rates of less than 1.0 per second the viscosity of suspensions of these two structural proteins is inversely proportional to shear rate. These results are consistent with previous in vivo measurements of the viscosity of cytoplasm. This power law implies that shear stress is independent of shear rate; that is, shear stress is a constant at all shear rates less than 1.0 per second. Thus the flow profile of these fluids is indeterminate, or nearly so. This flow property may explain several aspects of intracellular motility in living cells. Possible explanations for this flow property are based on a recent model for semidilute suspensions of rigid rods or a classical friction model for liquid crystals. PMID- 2881356 TI - Acquired immune deficiency syndrome--an overview. PMID- 2881357 TI - [Frequency as the cardinal determinant for electroacupuncture analgesia to be reversed by opioid antagonists]. PMID- 2881358 TI - [Sermion]. PMID- 2881359 TI - Bacterial adherence and urinary tract infection. AB - Bacterial adherence is important in the initiation of disease of the respiratory, gastrointestinal, and urinary tracts. This article reviews the mechanisms by which it occurs and presents specific examples of its importance in urinary tract infections. PMID- 2881361 TI - Studies in dental sedation and anaesthesia. PMID- 2881360 TI - Thiamine deficiency in black male hostel-dwellers. The need for thiamine supplementation of sorghum beer. AB - Some indices of nutrition have been examined in hostel- and non-hostel-dwelling groups of industrially employed black males. Hostel-dwellers in the large metropolitan areas have to prepare their own food and many are accustomed to excessive alcohol intake, especially of sorghum beer. In the two groups studied, blood levels of vitamin B12, folate, pyridoxal and albumin were similar, but erythrocyte thiamine levels were significantly lower in the hostel-dwellers. Although the proportion of subjects with elevated levels of gamma glutamyltransferase, an index of alcoholic liver disease, was similar in the two groups, thiamine-deficient hostel-dwellers had a greater proportion of elevated values suggesting that thiamine deficiency was related to both inadequate diet and excessive alcohol consumption. Fortification of sorghum beer with thiamine might prevent or reduce thiamine deficiency in this group. The cost would not materially affect the price of the beer. PMID- 2881362 TI - [Changes in cerebral and central hemodynamics in response to hypotensive therapy of patients with essential hypertension and different types of circulation]. AB - A study of indices of the cerebral and central hemodynamics in 122 patients with essential hypertension revealed differences in indices of the cerebral blood flow depending on the initial hemodynamic type. It was shown that the assessment of initial indices of the central hemodynamics makes it possible to achieve more favorable hemodynamic rearrangement, and an analysis of the cerebral hemodynamics -to foresee the inclusion of drugs correcting the cerebral blood flow in multimodality antihypertensive therapy. PMID- 2881363 TI - [Prolonged use of beta-blockers in patients with essential hypertension and different degrees of severity of left ventricular hypertrophy]. AB - The paper is concerned with analysis of the results of therapy with beta-blockers of different classes of 56 patients (over 2.5-3 yrs) with essential hypertension and analysis of the time course of the structural-functional states of the left ventricular myocardium with various degree of expression of left ventricular hypertrophy (LVH). The patients were divided into 3 groups: the 1st group--14 persons (the left ventricular myocardial mass/LVMM/up to 150 g); the 2nd group- 19 persons (the LVMM up to 200 g); the 3rd group--23 persons (the LVMM over 200 g). Patients in all the groups showed a significant decrease in BP from 19/15 up to 26/22% (p less than 0.001), the cardiac index (CI) from 14.4 up to 18.5% (p less than 0.001), and HR from 16.5 to 19.1% (p less than 0.001). The stroke index (SI) did not change significantly. The total peripheral vascular resistance (TPVR) in all the groups showed a tendency to a decrease, in the 3rd group only it decreased significantly. In the patients of the 1st and 2nd groups end systolic sizes (ESS) increased by 4.1 and 3.1% (p less than 0.05) and volumes (ESV) by 9.7 and 7.4% (p less than 0.05), and in the 3rd group a tendency to a decrease was observed. End-diastolic sizes and volumes in all the groups did not change significantly. The myocardial contractility index (VCF) decreased significantly in the 1st and 2nd groups of patients. The value of intramyocardial tension ("sigma max") decreased in all the groups from 15 to 20% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881364 TI - Enhancement of cytogenetic damage by inhibitors of poly(ADP-ribose)polymerase in human lymphocytes exposed to antineoplastics in vivo and in vitro. AB - The effect of benzamide (B) and 3-aminobenzamide (3-AB) on sister chromatid exchanges (SCEs) and cell kinetics induced in vitro by melphalan (MELPH) or thiotepa (THIO) was studied in normal human lymphocytes. The combined treatments with either MELPH or THIO plus B or 3-AB showed the potentiating ability on SCE rates and the ability to induce cell division delays of the latter chemicals. In a combined in vivo and in vitro study, lymphocytes taken from six cancer patients who had been given cytoxan by injection 2 hr before and then treated with theophylline (THEOPH) or B or 3-AB in vitro were found to have synergistically increased exchange rates and cell division delays. The frequency of SCEs in the patients own lymphocytes with and without exposure to inhibitor of Poly(ADP ribose) polymerase (P(ADPR)polymerase) was determined before the cytostatic therapy and was used as a control for later comparison in each individual case. These results further substantiate the use of this approach for detecting the induction of cytogenetic damage concerning controlled mutagen human exposure in combined in vivo and in vitro studies. Chemically induced cytotoxicity manifested as an alteration (division delay) in cell kinetics and as synergistic DNA damage by cytostatics and inhibitors of P(ADPR)polymerase may be of use in the treatment of human cancer. PMID- 2881365 TI - Expression of the major heat shock protein (hsp 70) family during early mouse embryo development. AB - Stress or heat shock proteins (hsp) are synthesized by most cells in response to adverse environmental conditions. In mammalian cells, the major proteins synthesized in response to stress have relative molecular weights (Mr) in the range of 68 to 74 kilodaltons (kD) and are encoded by a small multi-gene family collectively referred to as hsp 70 genes. In unfertilized mouse eggs, no members of the hsp 70 family appear to be synthesized under normal or stressful (heat shock) conditions. At the two-cell stage, two proteins with Mr = 74 kD and Mr = 70 kD are expressed as a consequence of developmentally activated transcription of these hsp 70 genes. No stress-induced synthesis in response to heat shock is observed at this stage. At the eight-cell stage, constitutive synthesis of the 70 kD protein continues, but, as in the two-cell embryo, no heat shock induced synthesis of a novel heat shock protein is observed. By the blastocyst stage, however, an inducible protein with Mr = 68 kD is synthesized in response to heat shock in addition to constitutive synthesis of the 70-kD protein. The constitutively synthesized cognate proteins are coded for by a set of mRNAs about 2,000 nucleotides in length. The induced hsp 68 proteins are coded for by mRNAs of larger size (about 2,600 nucleotides). Only the smaller mRNA class is detectable on Northern blots of RNA extracted from control or heat shock cleavage stage embryos and control blastocysts. As predicted from protein synthetic studies, both classes are resolved in RNA preparations derived from heat-shocked blastocysts. PMID- 2881366 TI - The direct-acting mutagenicity of nitroimidazo[2,1-b]thiazoles in Salmonella typhimurium. AB - A series of nitroimidazo[2,1-b]thiazole derivatives was investigated for direct acting mutagenic potency with the Salmonella assay. All of the nine derivatives tested were mutagenic. The compounds induced predominantly base displacements resulting in frame-shift mutations. The mutagenic activity did not require the S9 fraction but was largely dependent on "classical" bacterial nitroreductase. The primary basis of the mutagenic activity of nitroimidazo[2,1-b]thiazoles appears to be a reduction of the nitro-function to the corresponding hydroxylamine. Mutagenicity seems to be paralleled by an increase of the nitro groups: dinitroderivatives were more active than nitroderivatives. Other electrophiles and sterically constrained nitro groups could account for differences in genotoxicity. PMID- 2881367 TI - Developmental effects of chemicals and the heat shock response in Drosophila cells. AB - Exposure of prokaryotic and eukaryotic cells to heat shock (hyperthermia) or to a number of diverse environmental stresses such as teratogens, anoxia, and inhibitors of oxidative phosphorylation results in the enhanced synthesis of a number of proteins which have been previously referred to as heat shock proteins (hsps). More recently, in view of the diverse types of agents that can induce these proteins, they have also been referred to as stress proteins. This phenomenon is one of the most basic regulatory mechanisms in living organisms. Exposure of Drosophila embryos, larvae, or pupae to these types of stresses also results in a variety of developmental abnormalities in the ensuing adult. Although the function(s) of these heat shock proteins has yet to be determined, they are widely thought to play an important role in cell survival and protection following some types of environmental stress. In our laboratory, we have developed an in vitro assay for detecting agents that act as teratogens, utilizing Drosophila embryonic cultures. Drosophila embryonic cells differentiate in vitro to a number of functional cell types including myotubes and ganglia. A number of drugs that have been shown to act as teratogens in mammals have also been found to inhibit muscle and/or neuron differentiation in Drosophila embryonic cultures. We have examined, by two-dimensional gel electrophoresis, the effects of such teratogens on protein synthesis in Drosophila embryonic cells. Inhibition of muscle and/or neuron differentiation correlates well with the induction of two proteins of about 20 kilodaltons. These are identical to two of the heat shock proteins (hsp 23, 22) as shown by electrophoretic mobilities and peptide mapping by partial proteolysis. Heat shock and other treatments such as exposure to some of the metal ions and ether induces the entire set of seven major heat shock proteins in the Drosophila embryonic cells. Dose-response studies of several teratogens show a correlation between the degree of inhibition of differentiation and the level of induction of hsps. Since heat shock proteins have been suggested as possibly serving a protecting role, our present studies are aimed at identifying the role of hsps in teratogenesis and investigating the differential regulation of heat shock genes in response to different external stimuli. PMID- 2881368 TI - Relationship between ossification and body weight of the CD-1 mouse fetus exposed in utero to anticonvulsant drugs. AB - The anticonvulsant drugs carbamazepine, Na valproate, and phenytoin have been suspected as a cause of human congenital defects. The malformations produced may include cleft lip and/or palate, heart defects, skeletal defects, and low body weights. Since the toxic effects of these anticonvulsant drugs manifest themselves in terms of fetal growth retardation, evaluation of the state of ossification attained in the fetus is important. In the present study, pregnant CD-1 mice received on gestational days 8-16 an oral dose of 375, 563, 938 mg/kg of carbamazepine; or 225, 338, 563 mg/kg of Na valproate; or 50, 75, 125 mg/kg of phenytoin. These groups were compared to two control groups. On day 17, the dams were killed by cervical dislocation and one-third of the live fetuses were weighed and fixed for skeletal examination. Photographs were taken of the fore- and hindlimb skeletons. From these photographs, the length and width measurement of ossified regions of the humerus and femur were determined using a Zeiss Video Plan Morphometrics Computer. Of the three anticonvulsant drugs studied, the greatest correlation between reduced fetal weights and retarded ossification of the long bones was phenytoin at the 125 mg/kg dosage. Our results also showed that long bone ossification, when compared to the fetal weight, indicated that 59 66% of variability in weight is predictable by bone measurements. PMID- 2881369 TI - Malformations induced in cultured rat embryos by enzymically generated active oxygen species. AB - Day 9.5 rat embryos were exposed in culture to xanthine/xanthine oxidase generated active oxygen species. Growth and development were assessed after 46 hr of culture. The treatment induced abnormalities of the neural suture, the severity of which increased in a dose-related manner with the concentration of substrate or enzyme. Glutathione (10 mM) or catalase (50 micrograms/ml) either partially or completely abolished the effects of xanthine/xanthine oxidase, whereas the addition of superoxide dismutase (50 micrograms/ml) or desferrioxamine (1mM) did not reduce the number of malformed embryos. These findings suggest that hydrogen peroxide and/or hydroxyl radicals are responsible for the effects of xanthine and xanthine oxidase. PMID- 2881370 TI - The heat-shock response in vivo: experimental induction during mammalian organogenesis. AB - According to the embryonic stress hypothesis of teratogenesis, anatomical malformation can be the consequence of the induction of a heat-shock response (HSR) in the embryo at some critical stage during the determination or differentiation of organs. This hypothesis states that a teratogen is any agent that is capable of inducing a HSR and that can reach the developing embryo. As a first step in determining whether the hypothesis is tenable, it was necessary to determine whether the embryo in fact is capable of making the HSR during the period of organogenesis. Pregnant mice were treated with two classical inducers of the HSR, one a physical and the other a chemical agent--namely, hyperthermia and sodium arsenite. The embryos, while still in the living mouse, responded with heat-shock protein induction, as did control bone marrow. PMID- 2881371 TI - Hyperthermia as a teratogen: a review of experimental studies and their clinical significance. AB - Although hyperthermia is teratogenic in birds, all the common laboratory animals, farm animals, and primates and satisfies defined criteria as a teratogen, its study as a human teratogen has been neglected. Homeothermic animals, including humans, can experience body temperature elevations induced by febrile infections, heavy exercise and hot environments which exceed the thresholds (1.5-2.5 degrees C elevation) which are known to cause a syndrome of embryonic resorptions, abortions, and malformations in experimental animals. Hyperthermia is particularly damaging to the central nervous system, and if a threshold exposure occurs at the appropriate stages of embryonic development, exencephaly, anencephaly, encephalocoele, micrencephaly, microphthalmia, neurogenic talipes, and arthrogryposis can be produced in a high proportion of exposed embryos, the incidence and type of defect depending on the species and strain within species, the stage of development, and the severity of hyperthermic exposure. Other defects which can be induced experimentally include exomphalos, hypoplasia of toes and teeth, renal agenesis, vertebral anomalies, maxillary hypoplasia, facial clefting, cataract, coloboma, and heart and vascular defects. Proliferating cells are particularly sensitive to temperature elevations, resulting in arrest of mitotic activity and immediate death of cells in mitosis with threshold elevations (1.5-2.5 degrees C) and delayed death of cells probably in S phase with higher elevations (3.5 degrees C). In general, lower temperature elevations (2.5 degrees C) require longer durations of elevation to cause defects than a simple spike at a higher elevation (4.5 degrees C). The death of cells is largely confined to the brain and in the day 21 guinea pig embryo to the alar regions of the brain. Cell death probably accounts for most of the defects in the central nervous system, but microvascular disturbances leading to leakage, oedema and haemorrhage, placental necrosis, and infarction are other known effects of hyperthermia; and these are probably involved in the pathogenesis of many defects of the heart, limbs, kidneys, and body wall. Recent experiments have demonstrated protection of rat embryos in culture against a known teratogenic exposure by a brief nonteratogenic exposure given at least 15 min earlier. This protection is associated with the synthesis of heat-shock proteins, and temporary arrest of the cell proliferative cycle. Hyperthermia appears to be capable of causing congenital defects in all species and may act alone or synergistically with other agents.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2881372 TI - [Persons with known alcohol problems. Screening procedures for alcohol consumption]. PMID- 2881373 TI - [Undescended testis. The results of 392 patients surgically treated with a standardized method]. PMID- 2881374 TI - [The empty scrotum. Etiology, assessment and treatment]. PMID- 2881375 TI - [Kallman's syndrome]. PMID- 2881376 TI - [Malignancy, fertility and undescended testis. Report of a patient with cancer of a solitary testis, and a review of the literature]. PMID- 2881377 TI - [Orchiopexy. Principles and technics]. PMID- 2881378 TI - [Intraoperative findings in 111 orchipexies]. PMID- 2881379 TI - [Polyarteritis nodosa]. AB - With reference to sixteen cases of polyarteritis nodosa (seven dogs, two cats, two goats, three pigs, two cattle), current views regarding classification, aetiology and pathogenesis of this disease are discussed. Polyartertis nodosa is not a disease entity, but rather a symptom that may be associated with various forms of disease and may vary in pathogenesis. The clinical picture depends upon the localisation of the vasculitis. Toxic agents and various viruses may be directly responsible for the vascular lesions. In addition, genetic, autoimmune and allergic factors may be implicated. The immunological pathogenesis is illustrated with reference to the serum sickness model. PMID- 2881381 TI - Circadian variations in hepatic glutathione content, gamma-glutamylcysteine synthetase and gamma-glutamyl transferase activities in mice. AB - Experiments were conducted to determine if the circadian variations previously observed in hepatic reduced glutathione (GSH) concentrations also occurred in the associated enzymatic activities involved in the synthesis (gamma-glutamylcysteine synthetase) and degradation (gamma-glutamyl transferase) of glutathione using male CF-1 mice. All parameters were measured at four hour intervals over a 24-h period under normal (L: 0600-1800 h) and reversed (L: 1800-0600 h) lighting schedules. Circadian rhythms were found in each parameter under both lighting schedules. With GSH content, the rhythms' peak occurred at 0200 h and the nadir at 1400 h under the normal lighting schedule and was reversed (peak: 1800 h; nadir; 0600 h) under reversed lighting. The enzymatic activities also varied in a circadian manner with a phase shift in the peak and nadir occurring with a change in lighting schedule. Liver weight varied in a circadian manner under both lighting schedules with greatest weights occurring at the end of the dark phase. These data show that not only does GSH content vary in a circadian manner but that associated enzyme activities do as well. However, the hepatic enzyme activities did not correlate well with the GSH rhythm and, thus, do not provide a mechanistic rationale for the GSH rhythm. PMID- 2881380 TI - HLA-DQ heterogeneity among HLA-DRw11(5) haplotypes. AB - Class II molecular variation among a panel of ten HLA-DRw11(5) homozygous cell lines (HCL) was investigated by analysis of restriction fragment length polymorphisms in genomic DNA. Hybridization of Bgl II, Hind III, and Taq I digested cellular DNA with DQ alpha and DQ beta cDNA probes identified a clustering of characteristic polymorphisms. Considerable diversity was observed between the HLA-DRw11(5), DQw3 positive haplotypes studied, as well as compared to a DRw11(5), DQw1 positive haplotype. In contrast to the observed DQ genomic variability, hybridization with a DR beta probe revealed relatively limited diversity. The molecular heterogeneity seen by genomic restriction fragment analysis illustrates the presence of genomic polymorphisms, particularly within HLA-DQ-related genes among a family of DRw11(5)-related haplotypes. PMID- 2881383 TI - Development and structure of the scientific program of the Eleventh Congress. PMID- 2881382 TI - Use of DNA restriction fragment length polymorphisms to document marrow engraftment and mixed hematopoietic chimerism following bone marrow transplantation. AB - We have studied the feasibility of using DNA restriction fragment-length polymorphisms (RFLP) to study marrow engraftment in 27 patients after allogeneic bone marrow transplantation, and have compared these results with those obtained using red blood cell antigens, cytogenetics, and immunoglobulin allotypes. Using highly polymorphic DNA probes, we have documented stable chronic mixed hematopoietic chimerism, have identified transient mixed chimeras, have excluded mixed chimerism with high probability in retrospective studies even when a pretransplant DNA sample was not available, have documented marrow engraftment in the early posttransplant period, and have studied the origin of leukemic cells in patients with recurrent disease. We have evaluated the advantages and disadvantages of several genetic markers and have developed tentative statements concerning the prognosis of patients with mixed chimerism. We conclude that DNA RFLP are powerful and practical genetic markers in bone marrow transplantation studies and that further studies of mixed hematopoietic chimerism are warranted. PMID- 2881384 TI - Association of restriction fragment-length polymorphisms with major histocompatibility complex class II phenotypes in white and black individuals. PMID- 2881385 TI - Prediction of risk factors in acute tubular necrosis following cadaver kidney transplantation. PMID- 2881387 TI - [Bacterial adhesion caused by fimbrial adhesins]. PMID- 2881386 TI - Mucinous breast carcinomas with abundant intracytoplasmic mucin and neuroendocrine features: light microscopic, immunohistochemical, and ultrastructural study. AB - Eight mucinous carcinomas of the breast were studied by light microscopy and immunohistochemistry; one was studied by electron microscopy. All 8 cases had abundant, relatively clear cytoplasm that contained mucin. Cells were argyrophil positive and argentaffin negative. Eight cases were positive for neuron specific enolase (NSE), 5 cases for serotonin, 1 case for serotonin and somatostatin and 2 cases for serotonin, somatostatin, and gastrin. None had clinical evidence of abnormal neuroendocrine function. Three patients had axillary lymph node metastases. Only 1 of 5 patients in whom there was clinical followup died of her disease. Electron microscopy of one case showed abundant intracytoplasmic and extracellular mucin, round and pleomorphic dense-core granules, numerous cell processes, and aggregates of intermediate filaments. These cases expand the histologic spectrum of breast carcinomas which may show neuroendocrine differentiation. PMID- 2881388 TI - [MAO inhibitors and anesthesia]. PMID- 2881389 TI - AIDS Transmission. PMID- 2881390 TI - Acetylated low-density lipoprotein is endocytosed through coated pits by rat peritoneal macrophages. AB - The surface distribution of the scavenger receptors for acetylated low-density lipoprotein (acetyl-LDL) and their endocytic behavior were studied by the direct immunoperoxidase method using monomeric conjugates of horseradish peroxidase with Fab' antibody raised against LDL. The receptors were demonstrated to be distributed diffusely on the surface membrane of cultured peritoneal macrophages, with preferential localization in coated pit regions. With temperature shift from 4 degrees C to 37 degrees C, acetyl-LDL bound to the surface membrane rapidly disappeared, but became detectable in coated vesicles or lysosomes. Further incubation in the presence of acetyl-LDL revealed lipid vacuoles devoid of a limiting membrane in the cytoplasm, transforming macrophages into typical foam cells. These data suggest that the binding of acetyl-LDL to its receptors triggers the clustering of the receptors into the coated pit regions through which acetyl-LDL is endocytosed by coated vesicles to be degraded in lysosomes with subsequent intracellular accumulation of cholesterol esters. PMID- 2881391 TI - Contact smear cytologic preparations of organ culture explant tissue. AB - The effects of cytologic sampling by contact-smear on the viability and morphology of epithelial tissues maintained as explants in organ culture were studied. Tracheal and pancreatic tissues from Syrian golden hamsters were maintained for 30 days in culture, and sampled cytologically at weekly intervals. Analysis of sequential Papanicolaou-stained smears demonstrates that explant tissues can be evaluated cytologically over time in vitro without apparent effects on either the tissue viability, histochemistry or morphology. Microscopic examination further reveals that cellular samples retain diagnostically significant cytomorphologic features of the in vivo tissues. These observations indicate that this technique is useful for understanding the long-term response to carcinogens of epithelial tissue maintained in explant organ culture. PMID- 2881392 TI - Effects of nicotine on phenotypic modulation and initiation of DNA synthesis in cultured arterial smooth muscle cells. AB - During the early stages of atherogenesis, as well as during in vitro cultivation, smooth muscle cells modulate from a contractile to a synthetic phenotype. This process includes the loss of myofilaments and the formation of an extensive rough endoplasmic reticulum and a large Golgi complex; it leads to decreased contractility and the commencement of cell growth and secretion of extracellular matrix components. In this paper, the effects of nicotine on adult rat arterial smooth muscle cells cultivated in vitro were studied by transmission electron microscopy and 3H-thymidine autoradiography. The results show that the drug speeded the initial rate of transition of the cells from contractile to synthetic phenotype in primary culture. Further, it stimulated the initiation of DNA synthesis in growth-arrested secondary cultures. Its effect was independent of other mitogens and additive to that of serum. The influences of nicotine, both on the modulation of the smooth muscle phenotype and the initiation of DNA synthesis, occurred at concentrations lower than those obtained in the blood after smoking and could contribute to the role of smoking as a risk factor for atherosclerosis. PMID- 2881393 TI - In vitro labeling and tissue autoradiography of splenomegaly associated with portal hypertension. AB - Sinus hyperplasia occurring in the congestive splenomegaly associated with portal hypertension is a interesting model of steady-state hyperplasia in an adult tissue. In vitro labeling of human splenic tissue with 3H-thymidine and the demonstration of S-phase cells by autoradiography was performed to investigate the proliferative activity of sinus-lining and cordal reticular cells in congestive splenomegaly compared with that in the normal spleen. The labeling index (%) of sinus-lining cells after 2 h incubation was 0.07 +/- 0.02 in the normal spleen and 0.26 +/- 0.03 in congestive splenomegaly (t = 4.553, P less than 0.005, n = 11). This result indicated that sinus-lining cells have a long life span and that their proliferative activity is increased in congestive splenomegaly. On the other hand, the labeling of cordal reticular cells and arterial and venous endothelial cells was sparse or absent in both congestive splenomegaly controls, and these cells do not appear to be involved in sinus hyperplasia. PMID- 2881394 TI - Stereological estimates of nuclear volume correlated with histopathological grading and prognosis of bladder tumour. AB - The aim of this retrospective study is to provide morphometric data which make grading of urinary bladder tumours objective and reproducible by stereological estimation of nuclear volume using the principle of estimating of the volume of particles of arbitrary shape. The study includes 92 specimens: 12 from normal bladder mucosa, and 80 from bladder tumours (15 grade I, 45 grade II, 19 grade III and one grade IV according to Bergkvist et al. 1965). After standard fixation, embedding, sectioning and hematoxylin-eosin staining, an unbiased estimate of the mean volume of nuclei sampled with a change proportional to the volume: (Formula: see text) was calculated. Here l0 is the length of the intercept through a test point hitting a nucleus measured in a random direction through the test point. The weighted means of nuclear volume in bladder tumours are spread over a wide range and show a strong correlation with the Bergkvist grade. Moreover, the relationship between the weighted mean volume of nuclei in bladder tumours and the prognosis is very good. Only one of 35 patients with a mean nuclear volume below 300 micron 3 died of bladder cancer whereas 18 of 19 patients with a mean nuclear volume above 500 micron 3 developed invasives tumours or died of their disease. This simple and fast estimate of nuclear volume seems to provide objective data of high prognostic value. PMID- 2881396 TI - Organisation of collagen fibrils in tendon: changes induced by an anabolic steroid. I. Functional and ultrastructural studies. AB - The organisation of tendon collagen fibrils has been studied by electron microscopy after treatment with an anabolic steroid hormone in a short-term and a long-term study. The effect of anabolic steroids is of interest because of their use in competitive sports and in clinical therapy. In a functional experimental model the unexpected occurrence of dysplastic as well as ruptured and dissociated collagen fibrils was revealed. The striking time-dependent collagen dysplasia and other pathological findings strongly suggest that in mice anabolic steroid treatment predisposes to tendon rupture especially when the animals are exercised. The possible underlying mode of action of anabolic steroid hormone on connective tissue is discussed. PMID- 2881397 TI - Organisation of collagen fibrils in tendon: changes induced by an anabolic steroid. II. A morphometric and stereologic analysis. AB - Morphometric and stereologic analysis of the organisation of collagen fibrils in tendon tissue after a treatment with an anabolic steroid hormone allowed the following observations: In a short-term study stereological data revealed a potent accumulation of collagen fibrils in the extra-cellular matrix after the administration of an anabolic steroid. Compared with controls, the anabolic steroid significantly increased the number of dysplastic collagen fibrils dependent on duration of treatment. Inter- and intrafibrillary dysplastic collagen fibrils possess characteristic diameter distributions which differ considerably from those of normal collagen fibrils. The functional significance of the changes in mean diameter, diameter distribution, numerical density and volume fraction of collagen fibrils in tendons following hormone treatment may be relevant to the use of these drugs in clinical practice and in competitive sports. PMID- 2881395 TI - Inhibiting effect of plasma from normal and tumour bearing mice on the mitotic rate of regenerating liver. AB - Plasma from normal mice and from mice bearing the ES2 transplantable malignant tumour was injected intraperitoneally at a dose of 0.01 ml/g body weight in partially hepatectomized mice. Control animals were injected with a solution of sodium citrate in saline. The recipients were killed at the first (14:00 hours/48 h). These times are the time of day and the number of h after partial hepatectomy and second (14:00 hours/72 h) peak times after partial hepatectomy. The number of colchicine metaphases per 1000 nuclei was determined for hepatocytes and litoral cells. A different effect was obtained with plasma from tumour-bearing compared with normal mice. Plasma from both sources when injected 26 h after partial hepatectomy (16:00 hours/26 h) inhibited the mitotic activity of hepatocytes at the next peak of regenerative activity (14:00 hours/48 h). The plasma from tumour bearing mice also inhibited the peak on the following day (14:00 hours/72 h), whereas plasma from normal mice had no inhibitory effect and, indeed, a compensatory wave was observed at this time. Furthermore, plasma from tumour bearing mice also showed an inhibitory effect at the first peak (14:00 hours/48 h) when injected at the time of partial hepatectomy (14:00 hours/00 h) or at 22 h before partial hepatectomy (16:00 hours/-22 h) whereas the injection of plasma from normal mice at these times had no inhibitory effect. In the litoral cells the injection of plasma from tumour-bearing mice made 22 h before hepatectomy (16:00 hours/-22 h) led to a stimulation of mitotic activity which was controlled at 14:00 hours/48 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881398 TI - Identification and analysis of Ebola virus messenger RNA. AB - Six messenger RNA species of Ebola virus were identified in infected Vero E6 cells. Virion RNA hybridizes to each of the mRNAs, confirming that Ebola virus possesses a negative-stranded RNA genome. The mRNAs are monocristronic transcripts, are synthesized in the presence of actinomycin D, and are polyadenylated. In vitro translation of mRNA preparations results in the synthesis of five authentic viral proteins and a putative unglycosylated form of the glycoprotein, demonstrated by immunoprecipitation with virus-specific antisera and SDS-PAGE. No mRNA species was detected for the polymerase (L protein) gene. PMID- 2881399 TI - [Effect of loading with Naftusia mineral water on the endocrine cells of the antral portion of the stomach]. PMID- 2881400 TI - [Schizophrenia and the minimal brain dysfunction syndrome]. PMID- 2881402 TI - [Pathophysiology of cardiac arrhythmias involving autonomic transmitters]. AB - In general cardiac arrhythmias of different types and origins may be attributed to only a few basic electrophysiological effects. These are: changes in impulse formation, in impulse conduction, and/or in refractoriness. Autonomic transmitters are able to exert these effects on the heart and may therefore also induce or support cardiac arrhythmias. The stimulation of sympathetic nerves to the heart (transmitter noradrenaline) enhances via adrenergic beta-receptors the formation of impulses in nomotopic and heterotopic pacemakers by increasing the slope of their slow diastolic depolarizations. In principle identical effects are exerted by noradrenaline on abnormal ectopic pacemakers. Moreover, so-called triggered activity resulting from early or delayed after-depolarizations may be induced by sympathetic activation. In the normal atrial or ventricular myocardium as well as in the specialized ventricular conducting system the sympathetic transmitters are without direct influence on the conduction velocity. However, in the AV node, conduction velocity is markedly increased by noradrenaline. In the depolarized myocardium noradrenaline favours the generation of slowly propagated responses and may thus help to induce arrhythmias due to reentry. The refractory period is shortened by noradrenaline in the working myocardium and in the specialized conducting system. The described effects of noradrenaline are attributed to an increase of the slow inward current (Isi) carried by Ca2+ and Na+ ions. Moreover, a shift of the activation kinetics of the pacemaker current (If) to more positive potentials is discussed. Under the influence of beta receptor blockers, certain effects of noradrenaline may be unmasked which are mediated by adrenergic alpha receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881401 TI - [Prevention of stress ulcer in intensive care patients]. AB - Critically ill patients are prone to stress-induced ulcerations in the upper gastrointestinal tract, which might lead to life-threatening bleeding. Therefore, an effective stress ulcer prophylaxis is absolutely indicated and H2-blocking agents, anticholinergics, antacids, sucralfate, enteral nutrition and prostaglandin E analoges are recommended. H2-blocking agents seem to provide effective prophylaxis, but severe side effects seem to limit their application. Most of all, as they are less effective as antacids and as they cause considerable costs. Additionally H2-blocking agents elevate gastric pH, thereby favouring microbic colonisation of gastric juice. Microorganism from gastric juice may reach the tracheobronchial system and lead to nosocomial pneumonias. The contaminated gastric juice may also be considered as endogenous source for sepsis and entero-colitis. The anticholinergic agent pirenzepine does not increase gastric pH and seems to be effective in neurological and neurosurgical intensive care patients. Antacids are effective in stress ulcer bleeding prophylaxis, but favour bacterial overgrowth, are badly tolerated by patients and cause a high amount of nursing time. Sucralfate seems to be as effective as antacids, is better tolerated and does not elevate gastric pH. The remaining acidity of gastric juice blocks bacterial contamination. After all, the smallest costs of effective stress ulcer prophylaxis, makes sucralfate to the medicament of first choice. However, in severely ill patients, a combined stress ulcer prophylaxis with two or more agents seems to be necessary. PMID- 2881403 TI - [Principles of neuronal information storage. Theories, methodology, experiments]. PMID- 2881404 TI - [Significance of hormones for sex specific brain differentiation and teratopsychophysiogenesis]. PMID- 2881405 TI - Senile dementia of Alzheimer's type--current concepts and prospects. PMID- 2881406 TI - [Electrophysiologic parameters for objectifying the processes of behavioral regulation in psychophysiology]. PMID- 2881407 TI - [Psychophysiology and occupational medicine]. PMID- 2881408 TI - [Psychophysiologic indications of mental stress using acral impedance plethysmography]. PMID- 2881409 TI - [The P300 component of the event-related brain potential as an indicator of the psychophysics of cognitive processes]. PMID- 2881410 TI - [Effect of variable significance identification on the P300 components of the event-related brain potential]. PMID- 2881411 TI - [Viral tumor markers]. PMID- 2881412 TI - [Treatment of discoordination of labor activity with the beta-adrenomimetic alupent]. PMID- 2881413 TI - [Gastroduodenal ulcer--changes in surgical therapy by long-term drug treatment]. AB - Routine use of H2 receptor blockers has helped to reduce the rate of selective vagotomies and has brought down the range of surgical ulcer patients. For peptic ulcer therapeutic medication has proved to be superior to surgery. Various studies were evaluated and have brought into focus questions of decision-making between medicamentous and surgical treatment of ulcer. Therapeutic approaches are recommended for emergency treatment of bleeding duodenal ulcer and recurrent ulcer. PMID- 2881414 TI - [Use of the immunomodulator levamisole in the complex treatment of juvenile schizophrenics with an unfavorable course]. AB - The authors investigated the effect of the immunostimulant levamisole on the immunological reactivity of schizophrenics and the resultant decrease in the therapeutic resistance of these patients toward psychotropic therapy. Thirteen patients with juvenile malignant continuously progressive schizophrenia were studied, using a double blind design of examination. The number of suppressor T cells in patients treated with levamisole increased from 16.6% to 22.8% (p less than 0.001) which was not observed in patients on placebo. It has been demonstrated that the immunological parameters in patients with juvenile malignant continually progressive schizophrenia can be fully recovered. Yet, the changes observed in the clinical picture were heterogeneous and unremarkable. The experimental findings suggest that the use of levamisole may be more effective in patients with less progressive forms of the disease. PMID- 2881415 TI - Synthesis of glutamate and aspartate in rat brain synaptosomes. AB - ATP and glutamine are the sources of endogenous ammonia in rat brain synaptosomes. The amount of endogenous ammonia formed from exogenous ATP is not sufficient to assure the maximum rate of aspartate and glutamate accumulation in the synaptosomes utilizing pyruvate + malate. Addition of exogenous NH4+ or depolarization of synaptosome plasma membranes with high K+ concentration led to a twofold increase in the rate of accumulation of these amino acids. This indicates that both exogenous and endogenous NH4+ is involved in the synthesis of aspartate and glutamate in nerve terminals. Accumulation of glutamate was stimulated by aminooxyacetate and inhibited by haloperidol which indicates that NH4+ is bound in the reaction catalysed by glutamate dehydrogenase. Endogenous oxaloacetate derived from pyruvate metabolism was the substrate for synthesis of aspartate. Additive inhibition of aspartate accumulation by fluorocitrate and (-) hydroxyacetate shows that, in addition to the tricarboxylic acid cycle, the reaction catalysed by ATP-citrate lyase serves in the synaptosomes as another source of oxaloacetate. PMID- 2881416 TI - The effect of fetectomy on prostaglandin receptors of the rat myometrium. AB - It has been postulated that intrauterine volume plays a role in the timing of parturition. In previous studies we found that the onset of parturition in the rat was associated with significant increases in the concentration of receptors for PGF2 alpha in the myometrium. To determine the effect of intrauterine volume on the concentrations of this myometrial receptor, we compared receptor levels in pregnant and fetectomized horns from unilaterally fetectomized pregnant rats near the time of parturition (n = 3). Myometria from pregnant horns contained substantially greater concentration of protein than did those from the contralateral fetectomized horns. The amounts of receptors per horn for PGF2 alpha were about 3 times greater in myometria from pregnant horns than in those from fetectomized horns. However, near term the concentration of receptors per protein contents was the same in pregnant and fetectomized horns. These results suggest that uterine stretch causes hyperplasia and hypertrophy of the myometrium being indicative of more protein per pregnant than fetectomized horns. However, the rise in the concentration of receptors for PGF2 alpha about the time of labour appears to be induced by hormonal and not by physical factors. PMID- 2881417 TI - Modifications of liver enzymes during heparin therapy. PMID- 2881418 TI - Glucose intolerance in thyrotoxicosis roles of insulin, glucagon and somatostatin. AB - The responses in plasma glucose, insulin, C-peptide, glucagon and somatostatin to an oral glucose load were studied in 10 thyrotoxic patients and 10 matched euthyroid controls. The thyrotoxic patients had higher mean fasting plasma glucose (P less than 0.05) and responded to oral glucose with an earlier peak at 30 min which was higher than the corresponding glucose level in the controls (P less than 0.05). Impaired glucose tolerance was found in 3 patients. Fasting insulin and C-peptide levels were normal in the thyrotoxic patients when corrected for the higher glucose levels. Following glucose ingestion, there was no significant difference between the areas under the insulin or C-peptide curves in patients and controls, but Seltzer's insulinogenic index was reduced in the patients (P less than 0.01) suggesting an impaired pancreatic B-cell response to oral glucose. Mean basal glucagon was normal in the thyrotoxic patients. However, while in the controls plasma glucagon became suppressed following glucose ingestion (P less than 0.0001), no significant suppression was found in the patients. In the thyrotoxic patients, mean basal somatostatin was normal, but the area under the somatostatin curve following glucose ingestion was significantly increased (P less than 0.02). Our findings suggest that decreased glucagon suppression and impaired insulin response after glucose ingestion are involved in glucose intolerance in thyrotoxicosis. Enhanced somatostatin responses to oral glucose in thyrotoxicosis may have contributed to the observed impairment in pancreatic B-cell responsiveness. PMID- 2881419 TI - Pre-operative treatment of 5 acromegalics with a somatostatin analogue: endocrine and clinical observations. AB - Five acromegalic patients were treated preoperatively over a period of 1-4 weeks with the somatostatin analogue SMS 201-995. The patients received daily 3 X 100 micrograms of SMS 201-995 subcutaneously. This schedule resulted in a rapid improvement of the clinical symptoms in 4 out of 5 patients. In these same patients plasma growth hormone concentrations decreased markedly. However, only in one patient were growth hormone concentrations normalized. Plasma IGF I, which was elevated in all patients, was normalized only in this same patient. Tumour volume as determined by thin section CT-scans decreased only in one case by 17%. All tumours appeared extraordinarily soft upon operation. Conventional light microscopy showed no difference between tumours of SMS-pre-treated and untreated patients. Ultrastructural investigation showed the usual heterogeneity. PMID- 2881421 TI - [Effects of cobalamin analogues produced by reaction between OHB12 and ascorbic acid upon absorption, plasma transport, organ distribution and B12 dependent enzymes]. PMID- 2881422 TI - Effect of a spirocyclic cyclodipeptide derivate of MIF on passive avoidance behavior and amnesia in rats. AB - Cyclo (1-amino-1-cyclopentane-carbonyl-L-alanyl)-c(Acp-Ala), a derivative of MIF (prolyl-leucyl-glycinamide) affected passive avoidance behavior of rats when administered at different phases of the step-through type of experimental paradigm. c(Acp-Ala) given s.c. or orally in a 1 mg/kg dose increased avoidance latencies not only when administered before, or immediately after the shock trial but also when given before the pretraining trial, i.e. at the first exposure of animals to the experimental situation without shock treatment. The notion is discussed, that it is the influence of c(Acp-Ala) on processing of information received during the pretraining trial that manifests itself in the facilitation of avoidance response. The drug appears to have a long-term action since it was active when given 20 h before the pretraining trial or the shock trial or the test of retention. c(Acp-Ala) when administered immediately after the shock trial, attenuated amnesia in rats induced by electroconvulsive shock (ECS). PMID- 2881420 TI - Naloxone enhances the increase in plasma growth hormone induced by alpha 2 adrenergic stimulation in healthy males. AB - There is evidence that the alpha 2-adrenergic agonist clonidine interacts with the opioid system. In the present investigations, the effect of naloxone on the increase in plasma GH induced by clonidine and the more specific alpha 2-agonist guanfacine was studied in man. In a single-blind study, five healthy males received in randomized order either the preservatives in the naloxone preparation (control) or naloxone at two different doses (10 or 100 micrograms/kg) followed by an infusion of either diluted preservatives or naloxone (5 or 50 micrograms X kg-1 X h-1, respectively). Fifteen min after the bolus dose, clonidine (3 micrograms/kg) or guanfacine (15 micrograms/kg) was infused over 10 min in a single-blind order. Both clonidine and guanfacine induced an increase in plasma GH (P less than 0.05). Pre-treatment with naloxone at the higher dosage resulted in an enhanced (P less than 0.05) GH response to clonidine and guanfacine, respectively, whereas the lower dosage of naloxone was without effect. The increase in plasma GH did not correlate with basal mean arterial blood pressure, nor with the changes in mean arterial blood pressure induced by clonidine or guanfacine. These results indicate that the increase in plasma GH induced by alpha 2-adrenergic stimulation in normotensive subjects involves opioid receptors with moderate sensitivity to naloxone. PMID- 2881423 TI - Alfentanil as an adjuvant of balanced anaesthesia for tonsillectomy in adults. AB - In a double-blind study, 80 adult patients, undergoing tonsillectomy, were randomly allocated to one of the four groups: d-tubocurarine (d-Tc) 50 micrograms/kg+alfentanil (Alf) 20 micrograms/kg, d-Tc 50 micrograms/kg+Alf 50 micrograms/kg, Alf 10 micrograms/kg+Alf 20 micrograms/kg, Alf 10 micrograms/kg+Alf 50 micrograms/kg. The first drug was given 2 min before thiopental and the second drug 1 min before inserting the mouth gag. Intubation was facilitated with suxamethonium. Anaesthesia was maintained with 70% nitrous oxide in oxygen and peripheral muscle relaxation during operation with vecuronium. For analysis of the induction characteristics, both d-Tc-pretreatment groups were treated together and compared with the results of the Alf pretreatment groups. Muscle fasciculations occurred in 20% in the d-Tc group and in 70% in the Alf group. Neither d-tubocurarine nor alfentanil prevented the cardiovascular intubation response. Cardiovascular responses to the placement of the mouth gag occurred only in the lower-dose alfentanil groups. ECG changes during operation occurred in 25-45% of the patients. The most common ECG change was junctional rhythm. The operating conditions were good in 65-80% of the patients. The mean recovery score (0-10) ranged from 9.3 to 9.7 between the groups. The incidence of nausea ranged from 20-30% and that of vomiting from 10 25% between the groups. Bleeding from the operation site occurred in 20-30% of the patients. None of the patients needed sutures to stop the bleeding. PMID- 2881424 TI - Neurotransmitter glutamate: its clinical importance. AB - Excitatory amino acid glutamate has several important functions in the mammalian central nervous system (CNS). This review focuses on the transmitter role of glutamate and discusses anatomical and pharmacological data of clinical neurological relevance. Experimental and clinical conditions which have been associated with altered content, uptake, membrane binding or release of glutamate in the CNS are discussed. Such conditions include, epilepsy, disorders of the basal ganglia, cerebral ischemia, hypoxia, hypoglycemia, metabolic encephalopathies, olivopontocerebellar atrophy and cerebellar ataxias, amino acidopathies, mental and other neurological disorders. With the exception of a few fibre systems, it is very difficult to differentiate between glutamate and aspartate as CNS transmitters. The term glutamate is, thus, used in the sense glutamate and/or aspartate unless specifically stated. PMID- 2881425 TI - Lymphocyte subset abnormalities in patients with spasmodic torticollis. AB - The aetiology of spasmodic torticollis is unknown but the patients form a heterogeneous group among which are cases apparently precipitated by a viral illness and others associated with autoimmune disease. We therefore decided to investigate the immunoregulatory lymphocyte subsets in our 11 cases. A significant decrease of both helper and suppressor lymphocytes was identified in the group, together with in vitro evidence of depressed suppressor cell function. Disturbance of the immune response may play a role in this puzzling disorder. PMID- 2881427 TI - Rating scales for states for anxiety, depression, mania and schizophrenia. A multiaxial approach. AB - Rating scales are considered to be an efficient instrument in the assessment of treatment effect, and during the last 25 years a number of rating scales has been constructed for measuring states of anxiety, depression, mania and schizophrenia. The paper describes some of the most frequently used scales. Time has come to coordinate the existing rating scales and to agree upon common operational definitions in the judgement of psychopathological symptoms. Basic practical guidelines to be used in both clinical practice and research are given. PMID- 2881426 TI - Specific chromosomal abnormalities characterize four established cell lines derived from malignant human gliomas. AB - The four permanent human glioma-derived cell lines reported here are the first such lines for which the karyotypes have been followed from the original biopsies through the establishment of the lines in culture. Although ploidy changes were seen, each line retained either distinctive marker chromosomes or the overall original chromosomal distribution allowing the origin of each line to be established with certainty. D-263 MG expresses glial fibrillary acidic protein, all lines except D-245 MG are tumorigenic in athymic mice, and each line displays a unique pattern with respect to in vitro growth parameters and expression of biochemically defined markers, oncofetal antigens and lymphoid-associated markers. D-245 MG and D-259 MG are able to grow in the absence of supplemental glutamine; glutamine synthetase was detected in these cell lines both by immunocytochemistry and by direct assay. Thus, the four permanent human glioma derived cell lines described here are representative of glioma lines in their general characteristics. D-259 MG retains numerous double minute chromosomes (DMs), D-263 MG contains two marker chromosomes with breaks in 9p, and D-247 MG and D-245 MG with stemlines containing 96 and 89 chromosomes contain eight and six normal copies (respectively) of chromosome No. 7. The retention in these four cell lines of the most common chromosomal abnormalities seen in biopsies of malignant human gliomas provides the opportunity to investigate the meaning of these specific chromosomal changes. PMID- 2881428 TI - Combination of psychotherapy and drugs in the treatment of neurosis. A controlled comparison of bromazepam and thioridazine. AB - Eighty out-patients with neurotic disorders were studied in an integrated treatment model combining psychotherapy and psychotropics in a "conjoint marital therapy" setting. The spouses, who seemed a healthy group, were used as reporters, as controls and as participants in the psychotherapy. The pharmacological trial was a double-blind, cross-over study, comparing bromazepam and thioridazine after a placebo period. Bromazepam was more effective in controlling different anxiety symptoms and demonstrated more potent activating properties than thioridazine. Hostility symptoms, however, responded better to thioridazine. These findings were confirmed by ratings performed by patients, spouses and the investigator. Differences in drug preference and drop-out rate showed the same tendency. Nine weeks' continuous treatment did not change the differences found in the cross-over study. No pharmacological rebound symptoms were observed after drug withdrawal. The personality of the spouses was related to the outcome in the patients. Moreover, there was an obvious positive interaction between the psychotherapy given and the drug treatment. PMID- 2881429 TI - [Intratubular calcifications in cryptorchism. Histochemical, morphometric and microanalytical study]. PMID- 2881430 TI - Peptides associated with eggs: mechanisms of interaction with spermatozoa. AB - Speract (Gly-Phe-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly), a peptide obtained from the culture medium of Strongylocentrotus purpuratus eggs, stimulates the respiration and motility of S. purpuratus spermatozoa under appropriate conditions. Resact (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg-LeuNH2), a peptide obtained from Arbacia punctulata eggs also stimulates the metabolism and motility of A. punctulata spermatozoa, however, it fails to stimulate S. purpuratus spermatozoa. Early biochemical responses of the spermatozoa to the egg peptides include a net H+ efflux and elevations of cyclic AMP and cyclic GMP concentrations. In addition, in A. punctulata spermatozoa, a major plasma membrane protein is modified in response to resact such that its apparent molecular weight shifts from 160,000 to 150,000. If cells are incubated with 32P, the 160,000 molecular weight form of the protein becomes radiolabeled; subsequent addition of resact causes a rapid loss of 32P from the protein. The plasma membrane protein appears to be the enzyme, guanylate cyclase; coincident with the shift in apparent molecular weight, enzyme activity decreases by as much as 90%. Since speract fails to cause these responses in A. punctulata, it can be concluded that the events are receptor-mediated. PMID- 2881432 TI - [25 years of Alpine skiing. In retrospect--the development and management of tibial fractures]. AB - Due to the advancement in the development of ski, technique, equipment and improvement of the slopes in the last decades, there has been a change in the type, form and location of fractures of the lower leg. In a 25 year follow-up at the department of traumatology of the University of Innsbruck we analysed the winter months of the year 1960/61, 1970/71, 1980/81 and the year 1984/85. A shifting of the localization of injuries towards the upper part of the body has been found. There is no doubt that because of the development of modern ski bindings lower-leg fractures have decreased significantly with adults. At the age between 11 and 15 years there has been no proportional change in the frequency of injuries. The operative treatment has increased in number in comparison with the conservatively treated fractures. PMID- 2881431 TI - Dephosphorylation of sea urchin sperm guanylate cyclase during fertilization. AB - Exposure of Arbacia punctulata spermatozoa to solubilized egg jelly results in the immediate dephosphorylation (within 3 sec) of an abundant 160,000 dalton (160 kDa) sperm membrane protein, and a simultaneous increase in its electrophoretic mobility to 150 kDa. The sperm phosphoprotein has been identified as guanylate cyclase. Correlated with the mobility shift of the cyclase is a decrease in its enzymatic activity. In this paper we will briefly review the work on the sperm guanylate cyclase, present new data on the role of ion fluxes in the control of its dephosphorylation, and discuss what role the dephosphorylation might play in successful sperm-egg interaction. PMID- 2881433 TI - [Diagnosis and treatment of frostbite]. AB - Pathophysiology, clinical picture with grading and in some cases controversial possibilities of treatment are described. We report on our experience in treatment of 21 cases of frostbite on hands and feet. Widening by DSA of the diagnostic spectrum of late sequelae is emphasized. PMID- 2881434 TI - [Interwoven wire suture with fascia lata-plasty in the treatment of subcutaneous rupture of the Achilles tendon--an obsolete method?]. AB - Lately there has been an increased incidence of rupture of the Achilles tendon following the general increase in mass sports. Surgery is the treatment of choice, and various methods are being described. We have been using the wire suture method with fascia lata plasty for more then twenty years. The rate of infection is 3.8% and that of rerupture 1.2%, figures that correspond to those stated for other surgical methods. Moreover, 87% of the patients were very satisfied with the result of the operation; they are fit for work without any restriction, and some of them even practise their sports activities as before. For this reason we consider that wire suturing with fascia lata plasty is by no means obsolete in the treatment of rupture of the Achilles tendon. PMID- 2881435 TI - [Rupture of the pes anserinus--a rare concomitant injury in anteromedial instability of the knee joint]. AB - We report about a case of rupture of the pes anserinus insertion causing an anteriormedial knee instability grade () without rupture of the anterior cruciate ligament. This case demonstrates that a grade ()-instability can be caused without rupture of the cruciate ligaments just by the rupture of a so called "dynamic stabilisator" like the pes anserinus. PMID- 2881436 TI - [Segmental fracture of the tibia]. AB - Segmental fractures of the leg, though rare, often imply serious complications. We present a concept of management which considers the impaired circulation to fracture fragments. In our opinion plate osteosynthesis and medullary nailing should remain the exception; closed methods have priority. In open fractures external fixation devices are preferred. PMID- 2881437 TI - [Surgical treatment of recurrent ventral dislocation of the shoulder using the Weber rotation osteotomy]. AB - There are different procedures for surgical treatment of a recidivating ventral dislocation of the shoulder. In our hospital the rotatory osteotomy according to Weber proved good; in accordance with the findings it can be combined with other procedures. The surgical procedures and our results are explained. In our opinion, this surgical treatment will effect, besides known results (rotation of head defect to lateral), an essential stabilisation of the joint, by means of strain exercised on M. infraspinatus and the upper part of M. teres minor. PMID- 2881438 TI - [Ileus in enterothorax caused by right-sided rupture of the diaphragm. A case report]. AB - The case described in this article shows an almost typical course with blunt abdominal trauma that occurred a long time ago, a primarily recognized but not surgically treated rupture of the diaphragm on the right side, and subsequently developing intestinal signs with recidivating attacks of jaundice caused by displacement of the liver with kinking of the bile duct. The relatively rare late complication of a right-sided enterothorax with ileus makes this a remarkable case and underlines once again the need for immediate or at least early surgery to avoid late complications. PMID- 2881439 TI - [Pathologic fracture of the navicular bone]. PMID- 2881440 TI - Management of the common cold. PMID- 2881441 TI - Autoradiographic distributions of neurotransmitter receptors in the human brains of Parkinson's disease and primate models of MPTP-induced parkinsonism. PMID- 2881442 TI - Ro 16-6491: a new reversible and highly selective MAO-B inhibitor protects mice from the dopaminergic neurotoxicity of MPTP. PMID- 2881443 TI - MPTP-induced parkinsonism in the common marmoset: behavioral and biochemical effects. PMID- 2881444 TI - Biochemical pathophysiology of Parkinson's disease. PMID- 2881445 TI - Progressive supranuclear palsy: anatomoclinical and biochemical considerations. PMID- 2881447 TI - Cognitive impairments in Parkinson's disease. PMID- 2881446 TI - Movement disorders in patients with coexistent neuroleptic-induced tremor and tardive dyskinesia: EMG and pharmacological study. PMID- 2881449 TI - Transmitter receptor alterations in Parkinson's disease. PMID- 2881448 TI - Clinical and neurochemical consequences of neuronal loss in the nucleus basalis of Meynert in Parkinson's disease and Alzheimer's disease. PMID- 2881450 TI - Mechanism of action of L-leucyl-glycinamide and its effect on Parkinson's disease. AB - PLG potentiates the action of levodopa in 6-OH-DA-treated rats. PLG plus levodopa is more effective than levodopa alone. PLG-treated rats have a decreased concentration of Leu-enkephalin in the caudate nucleus as compared with the control. Preliminary results of using PLG (400 mg/day) for 10 days for treating PD are satisfactory. The mode of action of PLG with relation to dopamine enkephalin interaction is discussed. PMID- 2881451 TI - Ultrastructural chemoanatomy of the basal ganglia: an overview. PMID- 2881452 TI - Dopaminergic-peptidergic interactions in extrapyramidal disorders: a review of the clinical evidence. PMID- 2881453 TI - Chronotropic cardiac effects of histamine in the conscious dog with chronic atrioventricular block: interactions with the autonomic nervous system. AB - Chronotropic effects of histamine and dimaprit were studied in the conscious dog with chronic atrioventricular block. Histamine at 0.2-5 micrograms/kg and dimaprit at equimolar doses (i.e. 0.25-6.25 micrograms/kg) increased atrial rate dose-relatedly. Blockade of muscarinic receptors reduced these effects and simultaneous blockade of muscarinic and beta-adrenergic receptors abolished them. Histamine and dimaprit moderately increased ventricular rate. Blockade of muscarinic receptors did not modify these effects, but blockade of beta adrenoceptors with or without simultaneous blockade of muscarinic receptors suppressed them. After blockade of beta-adrenoceptors, histamine and more rarely dimaprit sometimes decreased atrial and ventricular rates. These effects were prevented by additional muscarinic blockade. Histamine and dimaprit lowered mean blood pressure to the same degree before and after each antagonist. The positive chronotropic effects of histamine and dimaprit, at these doses, are probably reflex responses to their hypotensive effects. The negative chronotropic effects of histamine after pindolol are due to muscarinic receptor activation. No evidence was found to implicate histamine-specific receptors in any of the chronotropic effects of histamine and dimaprit. PMID- 2881455 TI - Pharmacology of the novel H2 antagonist famotidine: in vitro studies. AB - The novel antiulcer drug famotidine was found to be a potent and selective inhibitor of histamine H2 receptors. Its activity on different parameters involving H2 receptors was higher than that of other compounds of the family: pA2 values were 8.33, 7.86 and 7.83 in the guinea pig atria, guinea pig papillary muscle and isolated rat gastric secretion, respectively. Apart from quantitative differences, famotidine differed from the other compounds, since it caused a competitive antagonism only at low concentrations and an unsurmountable antagonism at higher concentrations. The duration of the inhibitory action on the "in vitro" gastric secretion resembled that of cimetidine and ranitidine. Famotidine was highly effective (approximately 10 times as potent as ranitidine) also on the rat uterus (unsurmountable antagonism) and on the guinea pig gallbladder (pA2 value = 7.71). Famotidine was apparently devoid of non-specific effects concerning the gastrointestinal motility even at very high concentrations (10(-4) M). In this respect, famotidine appeared to be more selective than cimetidine and ranitidine at the H2 receptor level. The high potency, the peculiarity of the antagonism and the lack of side-effects on a number of isolated preparations, indicate this H2 antagonist as a very peculiar member of the group. PMID- 2881454 TI - H2-receptor antagonist and gastric acid antisecretory properties of Wy-45,662. AB - Investigations were carried out to delineate the biological activity of Wy 45,662, a new H2-receptor antagonist. In the pylorus-ligated rat after intraduodenal administration, total acid output (TAO) over 4 hours was inhibited by Wy-45,662 with an ED50 of 0.3 mg/kg as compared to ranitidine (ED50 = 7 mg/kg) and cimetidine (ED50 = 12 mg/kg); i.v. or i.m. administration increased Wy 45,662's potency 10-fold. In dogs with innervated gastric pouches Wy-45,662 inhibited food-stimulated TAO with ED50's of 0.35 mg/kg (p.o.), 0.045 mg/kg (i.v.) and 0.065 mg/kg (i.m.); cimetidine (ED50 = 6 mg/kg p.o.) and ranitidine (ED50 = 1 mg/kg p.o.) were less potent. Wy-45,662 also inhibited pentagastrin- or histamine-stimulated acid secretion in the conscious fistula rat. In vitro, Wy 45,662 antagonized the histamine-stimulated a) positive chronotropism in guinea pig atria and b) [14C]aminopyrine uptake by rat gastric mucosal cells, confirming its H2-receptor antagonist properties. PMID- 2881456 TI - Inhibitory effect of famotidine on cat gastric secretion. AB - The inhibitory effect of the novel H2 receptor antagonist famotidine was studied in conscious gastric fistula cats against dimaprit-induced hypersecretion, in comparison with ranitidine. On the secretory plateau induced by dimaprit (2 mumol kg-1 h-1) famotidine (0.05-0.2 mumol kg-1 i.v.) exerted a dose-dependent inhibitory effect, being approximately 4.5 times as potent as ranitidine (ID50 values were 0.067 +/- 0.015 and 0.30 +/- 0.025 mumol kg-1 for famotidine and ranitidine, respectively). No significant differences were found between the two drugs, as for the time-course of the inhibitory effect. Famotidine (0.01-0.32 mumol kg-1 h-1) caused a parallel displacement of the dose-response curve to dimaprit to the right, without reducing the maximum response to the stimulant, thus behaving as a competitive antagonist, like ranitidine. pA2 values for famotidine and ranitidine were 7.95 and 6.92, respectively. In the same range of doses famotidine dose-dependently reduced also the secretory response to histamine. From these data it was concluded that famotidine is a potent histamine H2 receptor antagonist in the cat gastric mucosa; moreover, conversely from "in vitro" data, the antagonism was surmountable even at the highest doses tested. In vivo experiment, therefore, did not reveal any particular feature of this compound, apart from the undoubtedly high potency, in comparison with other members of the family. PMID- 2881458 TI - Beta-agonists can depress oxidative metabolism of alveolar macrophages. PMID- 2881457 TI - Role of T lymphocytes in murine collagen induced arthritis. PMID- 2881459 TI - Disturbance of mice tracheal beta-adrenoceptor and cholinergic receptor function by Bordetella pertussis and its cell wall components. PMID- 2881460 TI - [Transglutaminase in the swine lens]. PMID- 2881462 TI - [Intracavernous injection of etilefrine hydrochloride in iatrogenic priapism]. AB - Intracavernous injection of etilefrine hydrochloride (1 or 2 mg) was performed on four patients with fully erected penis after intracavernous injection of 40 mg of papaverine hydrochloride. One case needed three injections of etilefrine hydrochloride (1 mg), but the erection disappeared in the other three cases within 10 minutes after a single injection of 2 mg of etilefrine hydrochloride. The injection resulted in complete detumescence and relief of the erection in all cases. These observations strongly suggest that the intracavernous injection of etilefrine hydrochloride is effective in treating not only iatrogenic priapism but also priapism due to other etiologies. Also, it might be useful to control erection time after intracavernous injection therapy for impotence. PMID- 2881461 TI - [A comparative double-blind trial of HSR-902 and butylscopolamine bromide for relieving colic in ureteral stone patients]. AB - The clinical efficacy and safety of HSR-902 (tiquidium bromide, Thiaton) in patients with spastic pain caused by ureteral stones were evaluated in a double blind comparative trial. A daily dose of 30 mg HSR-902 or 60 mg butylscopolamine bromide as a control drug was orally administered for 7 days. With either drug marked improvement of spastic pain was observed. The time to obtain relief from spastic pain and utility rating were significantly more excellent with HSR-902 than with butylscopolamine bromide. With all other parameters used no significant difference was observed between the two drugs. Mild adverse effects such as abdominal discomfort and constipation were observed in 2 of the 87 cases in the butylscopolamine bromide group but none of the 83 cases in the HSR-902 group. Taking efficacy and safety of the treatment into consideration, no significant difference was observed in usefulness between the two drugs, and we were able to confirm the usefulness of HSR-902 for relief from spastic pain caused by ureteral stones. PMID- 2881463 TI - BLV receptor activity in plasma membranes from tumorous lymph nodes of BLV infected cows. AB - Plasma membranes of cells from lymph nodes of bovine leukaemia virus (BLV)-free cattle and of cells from tumorous lymph nodes of BLV-infected cattle have been investigated for their reactivity with iodine labelled BLV antigens gp51 and p24. It has been found that only the plasma membranes from cells of tumorous lymph nodes bound gp51 and p24. The binding could be abolished by addition of nonlabelled antigens. It has been calculated from Scatchard plot analysis that 10(5) molecules of gp51 or 10(4) molecules of p24 can be bound per tumour cell. The findings led to the conclusion that tumour cells of BLV-infected cattle are endowed with receptors for the BLV antigens gp51 and p24. PMID- 2881464 TI - Demonstration of a thymus cell tumour in BLV-infected cattle. AB - Occurrence of thymus cell tumours was followed in cattle with enzootic leukosis using a thymus-specific antiserum. Among 32 tumorous lymph nodes investigated, one could be identified as a thymus cell tumour. In the DNA extract from this tumorous lymph node BLV-specific sequences have been demonstrated. This finding disproved the hitherto assumption that BLV-induced lymph node tumours of cattle were derived exclusively from B-lymphocytes. PMID- 2881465 TI - Propagation of hepatitis A virus in human diploid fibroblast cells. AB - Human hepatitis A virus (HAV) was propagated in human diploid fibroblast cultures (2BS cells) in vitro. Replication of the virus was followed by immunofluorescent staining (IF), indirect ELISA, and by immune electron microscopy. When 2BS cells were inoculated with faecal extracts containing HAV, synthesis of hepatitis A antigen (HAAg) could be detected in the cytoplasm by IF. Its concentration reached a maximum at four weeks post-inoculation. Measured by solid-phase indirect ELISA, the positive/negative (P/N) ratio for HAAg reached values of up to 7.7. The identity of newly synthesized virus particles with HAV was established by immune electron microscopy, IF-blocking, and neutralization with human convalescent serum. Infected cells showed no signs of a specific cytopathic effect. Two of the virus strains propagated in 2BS cells may prove useful as a source of antigen for serologic tests; one of them might be a candidate strain for HAV vaccine. PMID- 2881467 TI - Coxsackievirus B4 heterogeneity: effect of passage on neutralization and mortality. AB - We have compared two CB4 isolates for virulence, tissue tropism, and antigenic drift using monoclonal antibodies. Both isolates replicated in C57B1/6 and Balb/c mice. The human isolate Edwards, recovered from a fatal case of encephalohepatomyocarditis, produced lethal infection in adult animals. Lethal infections were associated with high viral titers in visceral organs but not with the presence of specific neutralizing epitopes. Virulence seemed stable upon passage, and also the avirulent JVB isolate retained its phenotype. Mock infection and recovery experiments demonstrated the stability of these characteristics. Neither the tissue from which the virus was isolated nor the cell line used in isolation significantly reduced virulence. However, antigenic variation among isolates was abundant. Thus, the set of monoclonal antibodies employed here may not be appropriate positive markers for virulence. This study suggests that CB4 virulence is stable upon extended in vitro passage and limited in vivo passage and that isolation site and method may not select for or against virulence. It is therefore possible that laboratory adapted strains of CB4, although antigenically different from freshly isolated specimens, may still retain these properties responsible for virulence present in low passage isolates and may be, with regard to virulence, very similar to freshly isolated specimens. PMID- 2881466 TI - Focus assay for varicella-zoster virus in human embryo cells stained with immunoperoxidase method. AB - Rapid titration of varicella-zoster virus (VZV) in human embryonic fibroblasts (HEF) based on staining of virus-infected cells by indirect immunoperoxidase technique (IPA) is described. Cell monolayers were grown in wells of plastic plates (two different diameters). Foci of virus-infected cells as revealed by IPA could be counted either 48 hr post-infection, if cell-associated virus (VZV infected cells) was used as inoculum, or 72 hr p. i. if cell-free virus was used. A linear relationship was observed between virus dilution and number of foci. The first virus was detected 12 hr p. i., the highest titre at 36 hr, when cytopathic effect (CPE) involved about 50% of the monolayer. PMID- 2881468 TI - Application of enzyme immunoassay on infected cells (EIA-IC) for arboviruses. AB - Comparative titrations of alpha-, flavi- and Bunyamwera viruses were made by EIA IC and according to cytopathic effect (CPE). Specific enzymatic reactions appeared earlier and in higher titres than CPE. The titres of dengue type 1, Mayaro, Powassan and Langat viruses measured by EIA-IC were comparable to those measured by intracerebral inoculation of mice. The cross-reactivity testing of EIA-IC among alphaviruses (Chikungunya, Sindbis and Mayaro), flaviviruses (Japanese encephalitis, Murray valley encephalitis, Kunjin, West Nile, yellow fever and louping ill, Powassan, Langat) and Bunyamwera arboviruses using polyclonal immune ascitic fluids confirmed the high specificity of EIA-IC. Homologous reactions mostly showed higher titres than heterologous ones. No cross reactivity was seen between alpha-, flavi- and bunyaviruses, among the three alphaviruses, between mosquito-borne and tick-borne flaviviruses, or between JE complex and YF viruses. However, a cross-reactivity to different extent was observed among the four JE complex viruses and among louping ill, Powassan and Langat viruses. The results of EIA-IC cross tests showed that this method can distinguish togavirus group- or species-specific antigens, more precisely than conventional ELISA. PMID- 2881469 TI - Ultrastructure of Rickettsia sibirica during interaction with the host cell. AB - Rickettsia sibirica (strain Netsvetaev) was found within large translucent spaces in the cytoplasm of L-929 cell monolayer cultures on day 6 postinfection (p.i.). These rickettsiae were rod shaped 0.3 X 10 microns in size encircled by a halo of up to 200 nm wide corresponding to a capsule-like coat. Directly on the cell wall was a 12 nm thick microcapsule in which subunit structures with 12 nm thick spacing could be recognized. The cell wall membrane was 14 nm thick with a wider internal layer occasionally in a section found split into two electron-dense lamels; the internal layer corresponded to peptidoglycan. The periplasmic space with an average thickness of 5 nm separated the cell wall from a 7 nm thick cytoplasmic membrane. The ultrastructure of R. sibirica was similar to that of other rickettsiae, although the capsule-like coat was thicker than in spotted fever (SF) group rickettsiae. PMID- 2881470 TI - Onset and duration of immunity in guinea pigs and mice induced with different Q fever vaccines. AB - Protective effects of different types of Q fever vaccines, namely untreated Coxiella burnetii phase I cells (Cb I) or Cb I cells treated with chloroform methanol (CM) mixture (Cb I-CM) and of a Q fever chemovaccine obtained by trichloroacetic acid extraction (TCAE) from intact Cb I cells, were compared in mice and guinea pigs at different intervals after intraperitoneal (i.p.) or subcutaneous (s.c.) immunizations. The highest degree of protection at all intervals studied was achieved with Cb I cells, irrespective of the route of immunization and i.p. or aerosol challenge. This vaccine exerted a protective effect in guinea pigs and mice as early as after one or two weeks post immunization, the effect lasting for at least 40 weeks in mice (i.p. challenge) and 12 months in guinea pigs (aerosol challenge). Addition of small amount of Cb I cells to TCAE increased resistance of guinea pigs to aerosol challenge. Degree, onset and duration of protection to either type of virulent challenge afforded by Cb I-CM cells and TCAE was similar, but when compared with that of Cb I cells it was lower, started later (from the 2nd week in guinea pigs and the 3rd week in mice), and in mice it lasted for a shorter period (20 weeks only). The resistance to virulent challenge in guinea pigs did not depend on the levels of microagglutination (MA) antibodies and in mice it was reflected by delayed type hypersensitivity (DTH) reaction and adoptively transferred splenocytes, rather than by MA antibody titres and passive transfer of immune sera to recipient mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881471 TI - Measles virus-induced mononuclear leukocyte adherence inhibition: effect of some drugs influencing arachidonic acid metabolic pathways. AB - Effect of some drugs influencing arachidonic acid metabolic pathways upon the measles virus-induced leukocyte adherence inhibition was investigated in multiple sclerosis patients and in the control group. The drugs used were natrium salicylate, ethanol, and phenidon(1-phenyl-3-pyrazolidon). Statistically significant differences were proved between multiple sclerosis patients and controls using phenidon, a drug inhibiting both cyclooxygenase and lipoxygenase pathways of the arachidonic acid metabolism. The results obtained provide suggestion on participation of arachidonic acid metabolism in the measles virus induced leukocyte adherence inhibition phenomenon and in its alterations in multiple sclerosis. PMID- 2881472 TI - Phenotypic mixing between vesicular stomatitis and Uukuniemi viruses. AB - The population of vesicular stomatitis virus (VSV) which reproduced in cells preinfected with Uukuniemi virus (UUK) contained a proportion of VSV (UUK) pseudotypes. The virions containing the VSV genome were resistant to anti-VSV serum and neutralized with anti-UUK serum. In addition to previous reports on phenotypic mixing of different families of enveloped viruses, the combination of rhabdovirus surface antigen with bunyavirus genome is described. PMID- 2881473 TI - Distribution of mouse cytomegalovirus in organs of white mice experimentally infected by natural route. AB - One, 10, 21-day-old and adult mice were inoculated by peroral and/or intranasal routes with mouse cytomegalovirus (MCMV). In animals surviving generalized infection, the virus could be demonstrated in salivary glands up to 123 days postinfection (p.i.). In mouse females which had eaten their infected and diseased offspring, the virus was detectable in salivary glands up to day 121, p.i. On day 16 p.i., the virus was present in salivary glands, lungs and kidneys of mice of different age groups, but no virus was recovered from their Gasserian ganglia. These results were compared with those obtained after infection with murine alpha herpesvirus. PMID- 2881474 TI - Tubular structures in cells of cucumovirus-infected Nicotiana glutinosa leaves. AB - Peculiar tubular structures about 250 nm in diameter were found in cells of Nicotiana glutinosa leaves infected with a cucumovirus strain isolated from field grown tobacco in southwest Slovakia. PMID- 2881475 TI - Persistence of coxsackie A13 virus in Balb/c mice with T-cell deficit. PMID- 2881476 TI - Use of concanavalin A treated PS cell cultures for the detection and assay of Japanese encephalitis virus from mosquitoes. PMID- 2881477 TI - Diagnosis and treatment of insomnia. AB - Insomnia is a disorder of initiation and maintenance of sleep that results in daytime somnolence. The differential diagnosis of the various forms of insomnia is based primarily on the history, including information from the sleeping partner. The possibility of underlying depression or sleep apnea must be given consideration in every patient with insomnia, because inappropriate therapy may be dangerous in these instances. In general, the benzodiazepines have supplanted the traditional hypnotics in the treatment of insomnia. PMID- 2881478 TI - Effects of beta blockade on systolic and diastolic left ventricular function at rest and during exercise in patients with chronic stable angina pectoris. AB - This study examined the effects of beta blockade with betaxolol, a cardioselective, lipid-soluble, beta-adrenergic-blocking agent, on rest and exercise systolic and diastolic left ventricular function in 15 patients, aged 40 to 70 years (mean = 52), with chronic stable angina pectoris. Each patient underwent three upright exercise studies at identical workloads; the first was a baseline study, the second was done 3 hours after a single oral dose, and the third was obtained after chronic therapy for 2 weeks. Beta blockade was evident by significant decreases in heart rate, systolic blood pressure, and diastolic blood pressure at rest and during exercise (p less than 0.04). Although there were no significant changes (at rest or during exercise) in mean left ventricular ejection fraction and peak filling rate, individual variations were seen after 3 hours and 2 weeks of therapy. During chronic therapy, the peak filling rate increased in three patients, decreased in five, and remained unchanged in seven. Also, discordant changes in systolic and diastolic functions were seen at rest and during exercise during both acute and chronic therapy. Thus, although acute and chronic beta blockade produces no significant changes in mean measurements of diastolic and systolic left ventricular performance, individual variations and discordant results are seen in many patients. The acute effects are generally consistent with the chronic effects, but exceptions are present. PMID- 2881479 TI - Usefulness of isoproterenol facilitation of ventricular tachycardia induction during extrastimulus testing in predicting effective chronic therapy with beta adrenergic blockade. AB - Previous studies indicate that programmed extrastimulus testing (PES) during isoproterenol infusion facilitates induction of clinical ventricular tachycardia (VT) in some patients. This study attempts to determine if VT inducible only during isoproterenol infusion predicts suppression of VT with chronic oral beta adrenergic blockade. Nine patients, aged 23 to 77 years, with symptomatic VT or syncope not necessarily provoked by exercise or stress were evaluated. Extrastimuli did not induce VT in any patient. However, during isoproterenol infusion (1 to 4 micrograms/min), all patients had reproducibly inducible VT corresponding to their spontaneously occurring VT (recordings available in 7 patients). Coupling intervals inducing tachycardia during isoproterenol were similar to intervals that did not induce VT without isoproterenol. No patient had VT with isoproterenol infusion alone (without extrastimuli). In only 4 of 8 patients who underwent exercise tests while not taking medications was VT provoked. With propranolol therapy (160 mg/day) or its equivalent, only 1 patient had recurrent symptoms during a mean follow-up of 39 months (range 23 to 52). VT inducible with extrastimuli only during isoproterenol infusion predicts that oral beta-adrenergic blockade will prevent spontaneous VT or syncope long term. These data suggest that occurrence of VT in some patients depends on premature depolarizations in the setting of beta-adrenergic influence. PMID- 2881480 TI - Effects of a new vasodilating beta-blocking drug, carvedilol, on left ventricular function in stable angina pectoris. AB - The effects of a new vasodilating beta-blocking drug, carvedilol, were studied in 20 patients with chronic stable angina using a single-blind, placebo-controlled protocol. Two doses of carvedilol, 25 mg twice daily and 50 mg twice daily, were compared with placebo using analysis of variance. The study design consisted of 2 weekly phases of initial placebo followed by carvedilol, 25 mg twice daily and then 50 mg twice daily, and a second placebo period. Supine rest and exercise radionuclide ventriculography was performed at the end of each phase. Carvedilol produced a significant dose-related reduction in rest and exercise heart rate and blood pressure (p less than 0.01 to less than 0.0001). Ejection fraction at rest increased significantly, from a mean (+/- standard error) of 53 +/- 3% with placebo to 58 +/- 3% with carvedilol, 50 mg twice daily, but no improvement was noted in ejection fraction on exercise. Relative, counts-based end-systolic and end-diastolic volumes were significantly reduced at rest (p less than 0.001). Rest peak filling rate index, first-third filling fraction and ejection rate index increased significantly with carvedilol. A dose-related change was observed with rest ejection fraction, peak filling rate index and ejection rate index. Exercise-induced ST-segment depression improved significantly with both doses of carvedilol compared with placebo. Carvedilol was well tolerated and produced significant hemodynamic improvement. This salutary effect on left ventricular function may confer advantages in long-term treatment of patients with chronic stable angina. PMID- 2881481 TI - Comparison of esmolol and nitroprusside for acute post-cardiac surgical hypertension. AB - Because acute systemic hypertension early after cardiac surgery has been linked to catecholamine elevation, an open-label, randomized, crossover study was performed to compare the efficacy of esmolol, a new ultra-short-acting intravenous beta-blocking agent, to nitroprusside, the standard therapy. Controlled drug infusions to maximal dosage (esmolol, 300 micrograms/kg/min, and nitroprusside, 10 micrograms/kg/min) were titrated to achieve at least a 15% reduction in systolic pressure. The blood pressure (BP) endpoint was achieved with esmolol (within 29 +/- 14 minutes) in 18 of 20 patients (90%), compared with 19 of 20 (95%) with nitroprusside infusion (within 21 +/- 15 minutes, difference not significant [NS]). Systolic BP decreased from 170 +/- 13 to 136 +/- 12 mm Hg (mean +/- standard deviation) with esmolol and from 170 +/- 13 to 141 +/- 13 mm Hg with nitroprusside infusion (both p less than 0.05). Diastolic BP was reduced from 71 +/- 12 to 64 +/- 11 mm Hg with esmolol and from 71 +/- 12 to 52 +/- 13 mm Hg with nitroprusside infusion (both p less than 0.05). Esmolol infusion resulted in decreased heart rate, cardiac index and stroke volume index and increased right atrial pressure (all p less than 0.05), whereas nitroprusside infusion resulted in increased heart rate and cardiac index and decreased right atrial pressure, pulmonary arterial wedge pressure and systemic vascular resistance (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881482 TI - Effects of soy polysaccharide on postprandial plasma glucose, insulin, glucagon, pancreatic polypeptide, somatostatin, and triglyceride in obese diabetic patients. AB - The effect of soy polysaccharide on postprandial plasma glucose levels was examined in a crossover experiment involving seven obese noninsulin dependent maturity-onset diabetic patients fed a standard meal without or with 10 g of this fiber source. Postprandial concentrations of plasma insulin, glucagon, pancreatic polypeptide, and somatostatin were measured to explore the mechanism of action. The effect on plasma triglyceride levels was also studied. Supplementation of soy polysaccharide significantly enhanced return of serum glucose levels towards fasting level during the latter half of the meal test. Addition of soy polysaccharide had no effect on plasma insulin levels but appeared (p greater than 0.05) to lessen postprandial increases in glucagon and pancreatic polypeptide levels while it raised somatostatin levels. Soy polysaccharide significantly reduced the rise of postprandial plasma triglyceride levels. The changes in plasma glucagon, pancreatic polypeptide, and somatostatin levels may have been instrumental in the observed postprandial glucose and triglyceride effects. PMID- 2881483 TI - Combined cyclophosphamide and corticosteroid-induced remission in severe glomerulopathy associated with systemic vasculitis. AB - Three patients with systemic vasculitis and severe renal disease as major manifestations are reported. In 2 cases, rapidly progressive glomerulonephritis presented as oliguric renal failure. In the third case, the clinical picture was severe nephrotic syndrome with decreased renal function. Combined cyclophosphamide and corticosteroid treatment resulted in dramatic improvement of renal function and remission of nephrotic syndrome. In 2 cases, histological improvement was documented by repeated kidney biopsy. The optimal duration of cyclophosphamide therapy has to be determined. PMID- 2881484 TI - Intracellular calcium during beta-adrenoreceptor blockade in essential hypertension. PMID- 2881485 TI - Selective suppression of hepatic glucose output by human proinsulin in the dog. AB - By using the euglycemic glucose-clamp technique we have observed the effects of comparable low dose proinsulin and insulin infusions on isotopically determined glucose turnover in 20 anesthetized dogs. In each animal somatostatin (SRIF) infusion was used to suppress endogenous pancreatic hormone secretion and basal glucagon was replaced. Peripheral proinsulin (0.083 micrograms X kg-1 X min-1) and insulin (350 microU X kg-1 X min-1) levels 15- to 20-fold higher than insulin on a molar basis, based on previous observations that proinsulin has only 5-10% the biologic potency of insulin. Three groups of infusion studies were performed: SRIF and glucagon (n = 5); SRIF, glucagon, and proinsulin (n = 10); and SRIF, glucagon, and insulin (n = 5). The mean serum proinsulin level of 2.43 +/- 0.36 pmol/ml achieved represented a 17-fold excess compared with the mean serum insulin level of 0.14 +/- 0.03 pmol (20 +/- 4 microU/ml). At these concentrations, both hormones reduced hepatic glucose production rates by approximately 50% to 2.0 +/- 0.2 mg X kg-1 X min-1 and 1.8 +/- 0.5 mg X kg-1 X min-1, respectively. In contrast, proinsulin failed to stimulate peripheral glucose utilization, whereas insulin led to a 2.0 +/- 0.3 mg X kg-1 X min-1 increment (approximately 50% increase) in glucose uptake (P less than 0.05). Thus at low infusion rates proinsulin exerts its effect predominantly by suppressing hepatic glucose production without measurable stimulation of peripheral glucose disposal. In contrast, for a comparable degree of hepatic glucose output suppression, insulin also significantly stimulates glucose disposal. PMID- 2881486 TI - Transport epithelial characteristics of cultured bovine pituitary follicular cells. AB - Confluent monolayers of polygonal epithelioid cells were obtained from enzymatically and mechanically dispersed bovine anterior pituitaries (AP) and pars tuberali (PT). The ultrastructure of the cells composing the monolayer was consistent with the follicular or folliculostellate cells (FC) of the pituitary, i.e., lack of secretory granules; formation of follicles in culture; interdigitations with neighboring cells with numerous tight junctions; presence of extensive microfilaments; and sparse rough endoplasmic reticulum and Golgi apparatus. Culture media from monolayers of first passage cultures contained little if any of the AP hormones' luteinizing hormone, prolactin, and ACTH. Shortly after reaching confluency, regions of the monolayer bulge away from the surface of the culture dish to form domes. Dome formation has been described only with cultures of cells that function as transport epithelia in vivo. FC cultured on polycarbonate filters were placed in Ussing chambers. A transepithelial potential difference of approximately 1.1 mV and a resistance greater than 300 omega cm2 were detectable 4-5 days after plating. The short-circuit current (Isc) was decreased 70% by amiloride applied to the mucosal surface and further decreased by the addition of ouabain at the serosal surface. The beta-adrenergic agonist isoproterenol increased the Isc and this action was prevented by a beta antagonist. These observations indicate that pituitary FC in culture behave as a transport epithelium. Considering the organization of FC in the AP and PT, they suggest a regulatory role for FC in the maintenance of the ionic composition of the interstitial fluid of the pituitary gland. PMID- 2881487 TI - Biological activity of progastrin posttranslational processing intermediates. AB - We recently identified carboxyl-terminally extended progastrin posttranslational processing intermediates in G cells of the gastric antrum and demonstrated that they are cosecreted with gastrin. To determine the physiological significance of these intermediates, we examined the biological activity of two synthetic gastrin precursor analogues that correspond to hexagastrin with carboxyl-terminal extensions, Tyr-Gly-Trp-Met-Asp-Phe-Gly (GL-7) and Tyr-Gly-Trp-Met-Asp-Phe-Gly Arg-Arg (GL-9) on gastric parietal and D cells isolated from canine fundic mucosa. Both analogues were as efficacious as gastrin heptadecapeptide in displacing 125I-[Leu15]gastrin from binding sites on the two cell types and in stimulating [14C]aminopyrine uptake by parietal cells and somatostatin release from D cells. However, both analogues were 10(4)- to 10(5)-fold less potent than gastrin heptadecapeptide in these activities. Our results indicate that progastrin processing intermediates do not have physiologically relevant actions under normal circumstances and support the notion that carboxyl-terminally amidated peptides such as gastrin require the amide moiety for biological activity. PMID- 2881488 TI - Electrical stimulation in perifornical lateral hypothalamus decreases coronary blood flow in cats. AB - Based on evidence implicating the central nervous system in the regulation of coronary vascular resistance and the knowledge that the hypothalamus is a central site for integration of cardiovascular control, studies were undertaken to determine if electrical stimulation in the hypothalamus produced coronary vasoconstriction. In anesthetized cats, following beta-adrenergic receptor blockade, stimulation in perifornical lateral hypothalamus produced a transient decrease in coronary blood flow velocity (30 +/- 5%), a small pressor effect (7 +/- 2 mmHg), and an initial decrease in hindquarter blood flow velocity (51 +/- 5%). The decrease in coronary flow velocity, which had an onset latency of 1-3 s and a duration of 5-15 s, was abolished by ipsilateral stellate ganglionectomy and by intravenous and intracoronary prazosin. The coronary vasoconstriction produced by hypothalamic stimulation was not different from that produced by cardioaccelerator nerve stimulation. These results suggest that electrical stimulation of a hypothalamic site produces an alpha-adrenergic receptor-mediated decrease in coronary blood flow that is unmasked by beta-adrenergic receptor blockade, requires the integrity of ipsilateral cardiac sympathetic innervation, and mimics the coronary response to cardioaccelerator nerve stimulation. PMID- 2881489 TI - Effects of dopamine in the renal vascular bed of fetal, newborn, and adult sheep. AB - The renal hemodynamic response to renal arterial dopamine infusions was compared in unanesthetized fetal (129-137 days gestation, full term 145 days), newborn, and adult sheep. Mean arterial blood pressure and heart rate remained unchanged during intrarenal dopamine infusions. Dopamine produced dose-related decreases in mean renal blood flow velocity in all three groups. When compared with adult sheep fetal sheep were slightly more sensitive to the vasoconstrictive effects of dopamine ED50 (mean effective dose ratio: fetus/ED50 adult = 0.368 +/- 0.047, P less than 0.05). Increases in mean renal blood flow velocity were not seen at any dose given (1-16 micrograms/kg body wt in fetuses, 2-32 micrograms/kg body wt in newborns and adults) until dopamine was infused during alpha- and beta adrenoceptor blockade. The largest mean increase in renal flow velocity was 13 +/ 3, 16 +/- 3, and 17 +/- 4% in fetal, newborn, and adult sheep, respectively. cis Flupentixol inhibited the vasodilation. This study demonstrates the presence of renal vasodilation following renal arterial dopamine infusions in fetal, newborn, and adult sheep when renal alpha- and beta-adrenoceptors are blocked. Vasodilator responses are similar in all three groups, and increases in renal blood flow velocity are small compared with that of other experimental models. PMID- 2881490 TI - Acute central effects of L-glutamate in pentobarbital-anesthetized dogs. AB - Microinjections of L-glutamate (10(-10) to 2 X 10(-8) mol/kg) into the nucleus of tractus solitarii produced a dose-dependent increase in mean arterial pressure and a decrease in heart rate. L-Glutamate-induced hypertension was prevented by spinal transection and pretreatment with atropine (1 mg/kg iv) reversed the bradycardia. L-Glutamate also produced a dose-dependent increase in mean arterial pressure when injected intravenously and into the cisterna magna, but the dose effect curves were shifted to the right. Finally, pretreatment with hexamethonium (30 mg/kg iv) abolished the hypertension resulting from intravenous injections of L-glutamate. These data demonstrate that the nucleus of tractus solitarii may play a determinant role in the central pressor effects of L-glutamate. In addition, we demonstrated that this hypertension was due to a central sympathetic stimulation and that the autonomic nervous system also mediated the pressor effects of intravenous L-glutamate. PMID- 2881491 TI - Aortic baroreceptor reflexes are mediated by NMDA receptors in caudal ventrolateral medulla. AB - The purpose of this study was to identify central nervous system pathways and synaptic receptors that participate in baroreflex control of arterial pressure. Microinjections of excitatory amino acids into the caudal ventrolateral medulla (CVM) of anesthetized rats evoked depressor responses analogous to baroreceptor reflexes. Functional inactivation of CVM neurons produced by microinjection of the gamma-aminobutyric acid receptor agonist muscimol completely abolished baroreflex-mediated decreases in arterial pressure elicited by electrical stimulation of the aortic nerve and markedly reduced depressor responses produced by the excitatory amino acid L-glutamate. In contrast, selective blockade of N methyl-D-aspartic acid (NMDA) receptors in the CVM abolished synaptically mediated depressor responses evoked by aortic nerve stimulation but not those elicited by L-glutamate, kainic acid, or quisqualic acid injected at the same site. These results indicate that the CVM contains an obligatory synapse in the central aortic baroreflex pathway; neural transmission of aortic baroreceptor information in the CVM is mediated by activation of NMDA receptors; and the neurotransmitter released at CVM synapses may be an excitatory amino acid. PMID- 2881492 TI - A biopsychosocial approach to treating patients with affective disorders. AB - The authors describe the development of an affective disorders consultation service that implemented a biopsychosocial model of subspecialty consultation within a university-affiliated community mental health center. They retrospectively analyzed the first 2 years of consultations, assessing the process of consultation and examining patterns of consultee inquiries and consultation recommendations. Consultants recommended combined psychopharmacologic and psychodynamic therapies for most patients and found psychodynamic psychotherapy strikingly overlooked by consultees, all of whom were psychiatrists or other mental health professionals. This evaluation documents the psychiatric consultees' deemphasis of the biopsychosocial perspective in clinical practice. PMID- 2881493 TI - Neuroleptic-induced akathisia treated with pindolol. PMID- 2881494 TI - Priapism treated with benztropine. PMID- 2881495 TI - Neuroleptics, prolactin, and osteoporosis. PMID- 2881496 TI - Dystonia, neuroleptic dose, and anticholinergic drugs. PMID- 2881497 TI - Drug interactions in surgical patients. AB - Drug interactions, defined as when the administration of a single substance (drug, nutrient, or tobacco) modifies the response to a drug, occur relatively frequently in surgical patients and may result in increased morbidity and lengthened hospital stay. Drug interactions also account for some instances of drug ineffectiveness or exaggerated pharmacologic response. There are many types of drug interactions. However, most of them are related to altered drug pharmacokinetic properties, where there are alterations in drug absorption, distribution, metabolism, or elimination; or altered drug pharmacodynamic actions, where two agents may have synergistic, additive, or antagonistic pharmacologic effects. The term, drug interaction, usually refers to pairs of drug substances administered concurrently, but more than two agents may be involved. When patients are taking a large number of different medications, there may be multiple drug interactions with additive or antagonistic effects, the overall effects of which are difficult to predict. There are hundreds of reported drug interactions, and some may be of important clinical consequence. In surgical patients, the majority of drug interactions involve histamine-2 blockers (particularly cimetidine), digoxin, warfarin, or a variety of agents that may be administered during anesthesia. Recognition of the potential for adverse drug interactions is of primary importance in minimizing their effects. Usually, potentially interacting drugs may be administered concurrently as long as appropriate patient or laboratory assessments are performed. For some agents, such as digoxin or theophylline, serum drug concentrations may aid in the avoidance of adverse drug interactions. PMID- 2881498 TI - Beta-adrenoceptor blockade and suxamethonium-induced rise in plasma potassium. AB - The effects of beta-adrenergic blockade on the suxamethonium-induced rise in arterial plasma potassium were studied in patients who presented for open heart surgery. No potentiation of the immediate rise in plasma potassium was observed. PMID- 2881499 TI - Bradycardia associated with the use of vecuronium. A comparative study with pancuronium with and without glycopyrronium. AB - One hundred and twenty patients undergoing anaesthesia for elective surgery received either pancuronium or vecuronium for muscle relaxation. Within each of these two groups, half were given glycopyrronium and the remainder an inert placebo. The incidence of bradycardia or bradydysrhythmias was higher in the group having vecuronium compared with those given pancuronium. Glycopyrronium afforded protection against undesirable vagal activity. PMID- 2881500 TI - Vecuronium--a variable dose technique. AB - Vecuronium was administered to patients in doses of 100, 150, 200 and 250 micrograms/kg and the duration of action recorded by noting the time to recovery of the first twitch in a train-of-four to 10% of the control twitch. The recovery times ranged from a mean of 28.4 minutes (100 micrograms/kg) to 72.4 minutes (250 micrograms/kg). It is suggested that for operations of medium to long duration the use of a large initial bolus dose of vecuronium is a technique with advantages over the use of an infusion or frequent incremental doses. PMID- 2881501 TI - [Initial experience with preorally administered dipotassium clorazepate and tilidine-naloxone in extracorporeal shockwave lithotripsy]. AB - After 70 treatments with extracorporeal shock wave lithotripsy (ESWL), using a combination of dipotassiumclorazepate p.o. 12 h before treatment and tilidin naloxon 45 min before ESWL, 56 patients reported to be painfree or only minor, well-tolerable pain. Informed consent was obtained in all patients for this pilot study, leaving the possibility of further pain medication. 7 patients asked for an additional analgesic (fentanyl) and another 7 patients required a sedative (midazolam). No further anesthesiologic procedures were necessary. Nausea was observed in one patient as a possible side-effect of tilidin. To confirm these preliminary results, a prospective randomized study is currently conducted. PMID- 2881503 TI - Venoconstrictor agents mobilize blood from different sources and increase intrathoracic filling during epidural anesthesia in supine humans. AB - The authors studied the effects of dihydroergotamine (DHE) and etilefrine hydrochloride (E) on the regional distribution of 99mTc-marked erythrocytes during epidural anesthesia in eight supine men to determine if vasoactive agents with venoconstrictor action would enhance cardiac filling during epidural anesthesia. Radioactivity was recorded with a gamma camera, and its distribution determined in the thorax, abdomen, and limbs. Arterial and central venous pressure, heart rate, and calf volume by plethysmography were measured. During epidural anesthesia with a sensory block up to T4/5, DHE (7.5 micrograms/kg) reduced the radioactivity, i.e., blood volume, in both the innervated (-5.9 +/- 3.5%) and denervated muscle/skin (-16.9 +/- 7%) regions, and increased it in both the intrathoracic (+7.0 +/- 2.3%), and splanchnic vasculature (+4.2 +/- 3.2). In contrast, E (6 micrograms X kg-1 X min-1) decreased the blood volume most markedly in the splanchnic region (-5.4 +/- 0.7%) and increased it in the thorax (+2 +/- 0.6%). All these changes were statistically significant. The combined effects were estimated to be equivalent to a transfusion of nearly 1.01 of blood. Both drugs reversed the hypotensive action of epidural anesthesia. During epidural anesthesia, DHE preferentially constricted the capacitance vessels in skeletal muscle and skin irrespective of the state of innervation, whereas E preferentially constricted the splanchnic vasculature. In the doses used, the two agents replenished in an additive fashion the central circulation during epidural anesthesia. PMID- 2881502 TI - The endocrine cells of the digestive system: amines, peptides, and modes of action. AB - The endocrine cells of the digestive system (entero-endocrine cells of gastro intestinal epithelia and Langerhans' islets of the pancreas) and the chemical messengers produced by them constitute a complicated and complex system. The physiological function of this system is the regulation of all processes related to digestion and resorption, and to homeostasis of carbohydrate metabolism. Using morphological and histochemical features of this cellular community, the present review deals with amines and amine metabolism, polypeptides and their immunohistochemical identification, and with the modes of action of enteric and pancreatic hormones. Special attention is paid to the significance of amine precursor uptake and decarboxylation (APUD), to immunohistochemical methodology and the interpretation of immunohistochemical findings, and to local regulatory mechanisms, especially paracrinia. Finally, unifying concepts for the integration of these cells and similar endocrine cells of other organs into a common system are considered. PMID- 2881504 TI - Pharmacokinetics of esmolol in anesthetized patients receiving chronic beta blocker therapy. AB - The pharmacokinetics of esmolol, a new, ultra-short-acting beta adrenergic blocking drug, were studied in 19 patients undergoing coronary artery surgery. Esmolol was administered as a continuous infusion, and blood concentrations were measured at intervals up to 40 min after discontinuation of the infusion. In all patients, a bi-exponential equation best described the esmolol concentration- time curve. Half-lives for the distribution and elimination phases were 1.34 +/- 0.77 min and 9.9 +/- 4.55 min (mean +/- SD), respectively. The mean values for V beta and V epsilon were 1.9 +/- 1.24 l X kg-1 and 0.41 +/- 0.31 l X kg-1, respectively, and the total clearance was 128 +/- 41 ml X kg-1 X min-1. PMID- 2881505 TI - The role of an ultra short-acting adrenergic blocker (esmolol) in patients undergoing coronary artery bypass surgery. PMID- 2881506 TI - Polymorphism and inheritance of swine small intestinal receptors mediating adhesion of three serological variants of Escherichia coli-producing K88 pilus antigen. AB - Brush borders, enterocytes, or both preparations obtained from the small intestine of 345 pedigreed pigs, carrying components of seven breeds, were tested by adhesion assay in vitro with 6-32 enteropathogenic Escherichia coli strains, each expressing one of the three K88 pilus antigens, K88ab, K88ac and K88ad. With few exceptions, all pigs were classified as belonging to one of four adhesion phenotypes: I I--corresponding to K88ab(-),ac(-),ad(-); II--K88ab(-),ac(-),ad(+); III--K88ab(+),ac(+),ad(-); and IV--K88ab(+),ac(+),ad(+). The non-adhering phenotype I was found to be the most frequent among the pigs tested, with the exception of one commercial herd, and this phenotype seems to be inherited as a recessive trait. The remaining three phenotypes are adhering, or are susceptible to adherence by one K88 variant, K88ad (phenotype II), by two variants, K88ab, ac (phenotype III), or by all three K88 variants, K88ab,ac,ad (phenotype IV). Phenotype II was found to be at low frequency, whereas III and IV occurred with similar frequencies. While the prevailing phenomenon was the bacterial adhesion to all, or none, of the brush borders, some pigs exhibited both adhering and non adhering brush borders, a mixed adherence phenotype. Preliminary segregation data, obtained from the F1 generation, seem to indicate that phenotypes III and IV correspond to two haplotypes with genes at two or three closely linked loci respectively. An alternative hypothesis is that the phenotypes III and IV are expressions of alleles at a single locus, each allele specifying a receptor able to bind two or three different serological types of K88 E. coli. PMID- 2881507 TI - Clinical profile of astemizole. A survey of 50 double-blind trials. AB - From clinical-pharmacologic and clinical data involving over 2,800 patients, astemizole appears to be a very effective and well-tolerated antihistamine. It is superior to placebo and commonly used antihistamines for the relief of rhinitis, particularly rhinorrhea and sneezing. It has a pronounced effect on ocular itching and lacrimation in conjunctivitis and on pruritus and wheals in urticaria. This superiority is due to a very specific, almost complete and sustained histamine H1-blockade. The clinical data confirm the experimental data in relation to its lack of sedative effects. PMID- 2881508 TI - [Drug-induced extrapyramidal syndrome]. PMID- 2881509 TI - [Cutaneo-systemic necrotizing vasculitis occurring during desensitization]. AB - The authors report a case of cutaneo-systemic necrotizing vasculitis, predominantly affecting the skin and digestive tract, observed in an asthmatic patient undergoing desensitization with Graminaceae pollen extract and mite enriched house dust. Vasculitis developed 22 months after the first injections, became autonomous after the end of treatment and responded well to systemic corticosteroid therapy in daily doses of 1 mg/kg. The patient was followed up for 8 months during which the vasculitis did not recur, despite reduction in steroid dosage. Reports of necrotizing vasculitis occurring during desensitization seem to be very rare. They raise the problem of whether specific immunotherapy plays a role in the pathogenesis of vasculitis. Most of the characteristics that emerged from the cases previously published are concordant with those found in our patient: the interval between the first injections and the initial symptoms varied from 45 days to 8 years; in every case the condition followed its own course after the injections were discontinued; most patients were being desensitized to several allergens; the cutaneous symptoms were pronounced, eosinophilia was moderate and hepatitis B serology was constantly negative. The few prospective studies aimed at determining, by different methods, the levels of circulating immune complexes (CIC) have given conflicting results. Atopic subjects have high CIC levels, but these do not seem to be influenced by desensitization. The nature of the CIC remains unknown, and the various suggestions put forward (cross-reaction between blocking IgG and auto-antibodies, CIC [blocking IgG, anti-idiotype antibodies]) require confirmation, although the hypothesis of pathogenic CIC (allergen, blocking IgG) is unlikely to be correct.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881510 TI - Somatostatin in the treatment of persisting pancreatic fistula--a report of two cases. AB - In two patients with persisting pancreatic fistula not responding to conventional treatment, definitive closure of the fistula was achieved when somatostatin was added to the treatment. PMID- 2881511 TI - [Somatostatin and regulation of the secretion of growth hormone]. AB - GH secretory bursts are due to the combination of a pulsatile GRF release and a decreased Somatostatin secretion in hypophysial portal blood. In the intermediary periods, low plasma GH levels depend on the tonic release of hypothalamic Somatostatin. Experimental studies suggest that alterations in hypothalamic Somatostatin are involved in changes of GH secretion observed under physiological (foetal life, aging, stress), pharmacological (beta-blocking agents) and physiopathological conditions (starvation, obesity, diabetes). The Somatostatin analogue SMS 201-995 induces a long-lasting inhibition of GH secretion and may be useful in the treatment of acromegalic patients. PMID- 2881512 TI - Myelopathies and retroviral infections. PMID- 2881513 TI - Chronic progressive myelopathy associated with elevated antibodies to human T lymphotropic virus type I and adult T-cell leukemialike cells. AB - Six adult patients had a chronic progressive myelopathy that possessed the following features: high antibody titers to human T-lymphotropic virus type I (HTLV-I) in serum and cerebrospinal fluid (CSF); predominantly upper motor neuron disorder, symmetrical, with mild sensory and bladder disturbances; and presence of adult T-cell leukemia-like cells in both peripheral blood and CSF. We refer to this entity as HTLV-I-associated myelopathy (HAM). Electrophoretic studies of immunoglobulin G in CSF using Western blot analysis characteristically demonstrated p24 and p32 bands. Rates of intra-blood-brain barrier synthesis were determined and found increased in the patients with HAM. Corticosteroid treatment produced clinical improvement in all of 4 patients. A retrospective survey of CSF samples was carried out in 287 patients with neurological disorders, and 6 additional patients with HAM were identified. PMID- 2881514 TI - Spinal cord stimulation affects the central mechanisms of regulation of heart rate. AB - The effect of spinal cord stimulation (SCS) on heart rate (HR) was studied in 25 patients without cardiological symptoms, who were undergoing SCS for various reasons. HR at rest significantly decreased during SCS. Physiological and pharmacological maneuvers of sympathetic and parasympathetic activation or blockade before and during SCS indicate that SCS interferes with the central mechanisms of regulation of HR mainly by inducing a functional sympathectomy, and that such an effect is mediated by an action on spinal cord ascending fibers. PMID- 2881515 TI - APUD-like cells in the primitive gut of a 27 day old human embryo. AB - A 27 +/- 1 days old human embryo arising from an ectopic pregnancy was incubated with 3,4, L-dihydroxyphenylalanine (L-DOPA) to investigate whether cells of the gut primordium have at this early stage of development, the ability to take up the amine precursors. We could observe that a few cells exhibiting greenish fluorescence were located in the epithelium wall of the fore gut. Most of them were situated in contact with the basal lamina and possessed a long apical process extending over towards the gut lumen. The uptake of amine precursor, the morphology and the location of these cells strongly suggest that they represent the gut endocrine precursor cells of the human embryo. PMID- 2881516 TI - [Polymorphism of restriction fragments, their use and animal selection]. PMID- 2881517 TI - Mechanistic studies on the "bronchosparing" activity of celiprolol, a cardioselective beta-adrenoceptor antagonist. AB - In some animal models, celiprolol, a cardioselective beta-adrenoceptor antagonist, has been reported to relax bronchial smooth muscle, an activity unique for this class of compound. Mechanistic studies with isolated cat tracheal rings and peripheral lung strips from guinea-pigs indicated that this relaxing activity could not be explained by competitive antagonism of serotonin receptors, beta- or alpha 1-adrenergic receptors, or histamine1-, leukotriene- or prostaglandin F2 alpha-receptors. Furthermore, this activity could not be explained by stimulation of beta-adrenergic or histamine2-receptors, nor can it be explained by a nonselective relaxing activity such as via the inhibition of cyclic nucleotide phosphodiesterases. Serotonin-induced contractions of isolated tracheal rings seem to involve a secondary process which could be the unmasking of alpha 2-adrenoceptors. It is this secondary process which appears to be affected by celiprolol; i.e. celiprolol could be a weak but selective antagonist of alpha 2-adrenoceptors associated with serotonin receptors. PMID- 2881518 TI - Alpha 2-adrenergic agonist and alpha 1-adrenergic antagonist activity of ergotamine and dihydroergotamine in rats. AB - The effect of ergotamine and dihydroergotamine on peripheral alpha-adrenoceptors was examined in pithed rats. The pressor response to ergot alkaloids was reduced competitively by yohimbine but not by prazosin or methysergide. These results show that the vasoconstriction induced by ergot alkaloids is mediated by alpha 2 adrenoceptors. Ergot alkaloids decreased the tachycardia elicited by stimulation of the cardioaccelerator sympathetic nerves, this effect being antagonized by yohimbine. The pressor response to (-)-phenylephrine was reduced by ergot alkaloids, suggesting competitive antagonism. It is suggested that in the pithed rat both ergotamine and dihydroergotamine act at the periphery as competitive alpha 1-adrenoceptor blockers and partial alpha 2-adrenoceptor agonists. PMID- 2881519 TI - Celiprolol, a compound possessing weak alpha 2-adrenergic antagonist properties in the dog. AB - Studies were conducted to evaluate the effects of celiprolol on alpha-adrenergic stimulation of dog saphenous vein rings (postsynaptic effect) and on catecholamine outflow from the dog coronary circulation during sympathetic nerve stimulation in vivo (presynaptic effect). In venous rings, celiprolol, 10(-6) to 10(-4) M, shifted the concentration-response curve to BHT 920 in a concentration related manner, but had no effect on the response to methoxamine at concentrations less than 10(-4) M. During continuous stimulation of the right stellate ganglion, celiprolol, 1-10 mg/kg i.v., increased the catecholamine concentration in the coronary sinus, while decreasing heart rate. In contrast, propranolol did not affect catecholamine concentration but decreased heart rate, rauwolscine increased both catecholamine concentration and heart rate, and clonidine decreased both catecholamine concentration and heart rate. These results are consistent with the hypothesis that celiprolol possesses weak alpha 2 antagonist properties in addition to its beta 1-blocking activity. PMID- 2881520 TI - Effects of pentazocine on the guinea-pig ileum. AB - The pA2 values for pentazocine-Ach, pentazocine-5HT and pentazocine-histamine antagonism on the guinea-pig ileum were found to be 8.0, 7.92 and 7.08, respectively. When the effects of a constant dose of pentazocine on equipotent doses of Ach, histamine, 5HT, and nicotine were studied, its anti-5HT and anti Ach activities were found to be equal and about 6.3 times higher than its antihistamine activity but 0.68 times lower than its anti-nicotine activity. The antihistamine activity of pheniramine was found to be 794 times that of pentazocine while the anti-Ach activity of atropine, the anti-5HT activity of cyproheptadine and the anti-nicotine activity of hexamethonium were 20, 10 and 2.2 times, respectively, higher than that of pentazocine. PMID- 2881521 TI - Vascular responses of isolated canine and simian femoral arteries and veins to alpha-adrenoceptor agonists. AB - Using isolated, perfused canine and simian femoral veins and arteries, vasoconstrictor responses to 6 alpha-adrenoceptor agonists and to potassium chloride were compared. The order of potencies of alpha-adrenoceptor agonists for inducing constriction was in canine arteries: epinephrine greater than norepinephrine = phenylephrine much greater than clonidine much greater than tyramine much greater than xylazine, in simian arteries: epinephrine greater than norepinephrine greater than phenylephrine greater than clonidine much greater than tyramine greater than or equal to xylazine, in canine veins: epinephrine greater than norepinephrine greater than phenylephrine greater than clonidine greater than or equal to xylazine much greater than tyramine, and in simian veins: norepinephrine = epinephrine greater than phenylephrine greater than clonidine greater than xylazine much greater than tyramine. A selective alpha 2 agonist, xylazine, did not induce any significant constrictor response in canine arteries, indicating a lack of alpha 2-adrenoceptors, but it induced significant constriction in 3 other vessels. In simian femoral arteries and veins dose response curves to each agonist were steeper than in canine vessels and potassium chloride induced much greater vasoconstriction than in canine vessels, indicating high sensitivity to extracellular calcium concentrations in simian vessels. The cannula inserting method would be useful for investigating pharmacological responses of isolated arteries and veins. PMID- 2881522 TI - Enhancement of morphine-induced hyperactivity by antihistaminic drugs in mice. AB - Three histamine H1-receptor antagonists, chlorpheniramine, diphenhydramine and tripelennamine, were tested alone or in combination with morphine on locomotor activity in C57BL/6 mice. All three antihistaminics, at some dosage levels, slightly increased activity when given alone, but strongly enhanced morphine induced hyperactivity. The results demonstrate that locomotor activity represents a useful test to evidence stimulatory effects of antihistaminic-opiate combinations. PMID- 2881523 TI - Update on rifampin drug interactions. AB - Rifampin, a potent inducer of the hepatic microsomal system, has been shown to cause clinically important interactions when combined with other drugs, including oral anticoagulants, oral contraceptives, digitoxin, methadone hydrochloride, sulfonylureas, and barbiturates. Additional literature on previously described interactions has been published recently on quinidine, glucocorticoids, digoxin, and theophylline. New rifampin interactions have been described for cyclosporine, ketoconazole, chloramphenicol, beta-blockers, verapamil, and phenytoin. These interactions seem to be of clinical significance. PMID- 2881524 TI - Beta-adrenergic blocking agents in the treatment of hypertension. Choices based on pharmacological properties and patient characteristics. AB - Drugs that block beta-adrenergic receptors have become one of the most widely used classes of drugs to treat hypertension. This review puts the use of beta blockers as monotherapy for hypertension in perspective and provides reasons for choosing among the several beta-blockers available. The major reasons for discriminating within this class of drugs are related to differences in concomitant clinical conditions, differences in patient responses, and intrinsic differences among the beta-blockers. These differences relate to special properties such as beta-agonist activity (intrinsic sympathomimetic activity), beta 1-selectivity, and concomitant alpha-blockade, as well as differences in side effect profiles, excretion characteristics, and length of action of the various drugs. PMID- 2881525 TI - [Clostridium perfringens type C enterotoxemia (necrotizing enteritis) in suckling pigs. 1. Study of the experimental production of disease by Clostridium perfringens type C poisoning and infection (experimental set-up, clinical aspects, pathological findings)]. PMID- 2881526 TI - [Clostridium perfringens type C enterotoxemia (necrotizing enteritis) in suckling pigs. 2. Light and electron microscopic studies of the pathology and pathogenesis of experimental Clostridium perfringens type C toxin poisoning]. PMID- 2881527 TI - [Clostridium perfringens type C enterotoxemia (necrotizing enteritis) of suckling pigs. 3. Light and electron microscopic studies of the pathology and pathogenesis of experimental Clostridium perfringens type C infection]. PMID- 2881529 TI - Graded exercise testing early after myocardial revascularization surgery. AB - The response to early graded exercise testing (GXT) was studied in 227 patients at a mean of 15.3 days after myocardial revascularization surgery (MRS). GXT followed a modified Bruce protocol without multiples of resting energy expenditure (MET) restrictions and a target heart rate (HR) of 90% of age predicted maximal HR. The decision as to precisely when to administer the GXT after surgery was made on an individual case basis by the cardiovascular surgeon and the attending cardiologist. For the data analysis, patients were grouped according to the number of days the GXT was administered after surgery: group 1, 7 to 14 days (n = 164); group 2, 15 to 28 days (n = 46); and group 3, greater than 28 days (n = 17). The use of beta blockers was also determined on an individual case basis by the attending cardiologist rather than on a random basis. Ninety-seven of the 227 patients were on beta blockers. Ventricular ectopic activity (VEA), ST-segment changes (STTC), peak HR, peak systolic blood pressure (SBP), peak rate-pressure product (RPP), and peak METs were assessed during exercise. No major complications occurred during testing. Approximately two thirds (67.4%) of the tests were terminated voluntarily by the patient, and 22.5% were stopped by the attending physician. Only 10.1% of the subjects reached the target HR. Chi-square analysis failed to reveal any association between time of testing after surgery and either STTC or VEA. Analysis of variance failed to reveal any effects of group or beta blocker on peak METs attained during GXT; however, patients not using beta blocker medication attained higher peak HR, SBP, and RPP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881528 TI - The use of psychostimulants in general psychiatry. A reconsideration. AB - A half century after the introduction of amphetamine sulfate (benzedrine), there remains active interest in the use of the major psychostimulants (ie, methylphenidate hydrochloride and pemoline) for the treatment of psychiatric disorders. In the absence of any recent review of the literature on the clinical uses of psychostimulants, we assessed the existing data on the adult psychiatric indications for these agents. Generally, the existing studies are old and inadequate. However, there is some evidence to support the judicious use of psychostimulants in selected clinical instances of several adult psychiatric syndromes. PMID- 2881530 TI - Testicular atrophy induced by di(2-ethylhexyl)phthalate: changes in histology, cell specific enzyme activities and zinc concentrations in rat testis. AB - Daily administration of 2g/kg/day di(2-ethylhexyl)phthalate (DEHP) to immature rats was found to cause testicular atrophy and reduce zinc concentration. Specific activities of testicular enzymes associated with postmeiotic spermatogenic cells, such as lactate dehydrogenase isozyme-X, hyaluronidase and sorbitol dehydrogenase, were lower than those of control by day 10, coincident with degeneration of spermatogenic cells. The specific activities of enzymes associated with premeiotic spermatogenic cells, Sertoli cells or interstitial cells (beta-glucuronidase, gamma-glutamyl transpeptidase and malate dehydrogenase) were higher than those of control by day 10. The specific activities of alcohol dehydrogenase and aldolase, zinc containing enzymes, increased after DEHP treatment in spite of the decrease in zinc concentration in the testis. In conclusion, changes in several testicular cell-specific enzymes appear to be useful biochemical markers of testicular injury induced by testicular toxicants such as DEHP. However, these changes occurred after or simultaneous with massive histological or morphological changes rather than prior to such changes. PMID- 2881532 TI - Epileptiform abnormalities discovered on electroencephalographic screening of psychiatric inpatients. AB - The results of electroencephalographic screening of 3225 inpatients from a community general hospital psychiatric service were reviewed. When patients with a prior diagnosis of epilepsy were excluded, epileptiform abnormalities were discovered in 2.6% of patients. Patients younger than age 25 years and patients with a diagnostic impression of anorexia nervosa, recent barbiturate abuse, or nonpsychotic explosive behavior were significantly more likely to have epileptiform abnormalities. The use of certain therapeutic agents was associated with a significant excess of epileptiform abnormalities in patients aged 25 years and older. The most frequently encountered epileptiform abnormalities were photoconvulsive responses. Focal temporal epileptiform abnormalities were detected in only four patients without a prior diagnosis of epilepsy. The diagnosis of epilepsy on the basis of a primarily psychiatric presentation and the discovery of epileptiform abnormalities on electroencephalographic screening should be approached with caution. PMID- 2881531 TI - The use of apolipoprotein CII as a genetic marker for myotonic dystrophy. AB - In five families we have confirmed the close linkage between the genes for myotonic dystrophy and apolipoprotein CII. The total maximum lod (log of the odds) score was 3.32 at 0 recombination. We demonstrate that the use of a Ban I restriction site polymorphism for apolipoprotein CII adds additional useful information when combined with the more commonly used Taq I polymorphism. The potential practical clinical use of these markers for the prenatal diagnosis of myotonic dystrophy is demonstrated. PMID- 2881533 TI - Congestive heart failure from betaxolol. Case report. PMID- 2881534 TI - Orchiopexy. PMID- 2881535 TI - Infectious disease in Antarctica and its relation to aerospace medicine: a review. AB - In many aspects, an Antarctic Station provides parallels to the environments encountered in space exploration, particularly with reference to infectious disease. In both instances, small groups of people live in isolation for long periods of time in a functionally sterile atmosphere. Therefore, studies of infectious disease in Antarctica should provide important insights into the experiences to be expected in spaceflight. This paper presents a summary of the information on the infectious and immunologic aspects of isolation derived over the years from research in Antarctica. PMID- 2881536 TI - Covalently bound pyrroloquinoline quinone is the organic prosthetic group in human placental lysyl oxidase. AB - Treatment of purified human placental lysyl oxidase with 2,4 dinitrophenylhydrazine (DNPH) resulted in a large spectral change and inhibition of enzyme activity. Proteolytic degradation of the derivatized enzyme yielded only one single coloured product, which was spectrally and chromatographically identical with the C-5 hydrazone of PQQ (pyrroloquinoline quinone) and DNPH. Since this represents the first example of a PQQ-containing enzyme in man, possible implications of the finding are discussed. PMID- 2881537 TI - Modulation of intracellular cyclic AMP content and rate of lipogenesis in mammary acini in vitro. AB - Relationships between the cyclic AMP content, the rate of lipogenesis and the activity of acetyl-CoA carboxylase in acini prepared from lactating rat mammary tissue were investigated by exposing them to agents that increase their cyclic AMP content in the presence or absence of insulin. The dose-dependent inhibition of lipogenesis by theophylline in acini isolated from fed rats was highly correlated with the induced increases in acinar cyclic AMP content. Cyclic AMP of acini from 24 h-starved lactating rats was more sensitive in its response to theophylline than that in acini from fed animals. Neither forskolin nor a mixture of isoprenaline and Ro 7-2956 were able significantly to change either the rate of lipogenesis or the activity of acetyl-CoA carboxylase in acini from fed rats when added to incubations in vitro, in spite of the large increases in cyclic AMP concentration produced by these agents. Insulin was without effect on the activity of acetyl-CoA carboxylase and on either the basal or isoprenaline stimulated cyclic AMP content of acini. These results are discussed in terms of the possibility that the rate of lipogenesis and the cyclic AMP content in mammary acini can vary independently of one another and of the activity of acetyl CoA carboxylase. PMID- 2881538 TI - Evidence that activation of acetyl-CoA carboxylase by insulin in adipocytes is mediated by a low-Mr effector and not by increased phosphorylation. AB - The activation of acetyl-CoA carboxylase (measured in a crude supernatant fraction) caused by insulin treatment of adipocytes was completely unaffected by the addition of a large amount of highly purified protein phosphatase to the supernatant fraction. Under the same conditions the inhibition of acetyl-CoA carboxylase by adrenaline was totally reversed. Experiments with 32P-labelled adipocytes showed that insulin increased the total phosphorylation of acetyl-CoA carboxylase from 2.7 to 3.5 molecules of phosphate/240 kDa subunit, and confirmed that this increase was partially accounted for by phosphorylation within a specific peptide (the 'I-site' peptide). Protein phosphatase treatment of the crude supernatant fractions removed over 80% of the 32P radioactivity from the enzyme and removed all detectable radioactivity from the I-site peptide. The effect of insulin on acetyl-CoA carboxylase activity, but not the effect on phosphorylation, was lost on purification of the enzyme on avidin-Sepharose. The effect on enzyme activity was also lost if crude supernatant fractions were subjected to rapid gel filtration after treatment under conditions of high ionic strength, similar to those used in the avidin-Sepharose procedure. These results show that, although insulin does increase the phosphorylation of acetyl-CoA carboxylase at a specific site, this does not cause enzyme activation. They suggest instead that activation of the enzyme by insulin is mediated by a tightly bound low-Mr effector which dissociates from the enzyme at high ionic strength. PMID- 2881539 TI - Muscarinic-agonist and guanine nucleotide activation of polyphosphoinositide phosphodiesterase in isolated islet-cell membranes. AB - Stimulated hydrolysis of the inositol phospholipids phosphatidylinositol 4 phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] was investigated by studying the phosphoinositides produced in a suspended preparation of plasma membranes by transference of 32P from [gamma-32P]ATP. At basal Ca2+ concentration (calculated free Ca2+, 150 nM) phospholipid hydrolysis was stimulated either by the muscarinic agonists carbamoylcholine and bethanecol or by the addition of the non-hydrolysable analogue of GTP, guanosine 5'-[beta gamma-imido]triphosphate [p(NH)ppG]. GTP was without effect on basal hyrolysis. Both GTP and p(NH)ppG enhanced the rapid (within 10 s) hydrolysis of PtdIns4P and PtdIns(4,5)P2 induced by carbamoylcholine in a dose-dependent manner. A rightward shift in the competition curve of carbamoylcholine for bound L-[3H]quinuclidinyl benzilate was seen on addition of GTP or p(NH)ppG (100 microM) under phosphorylating conditions. Pretreatment of intact islet cells with Bordetella pertussis toxin, islet-activating protein (IAP) or treatment of membranes with IAP under conditions which elicited ADP-ribosylation of a protein of Mr 41,000 was without effect on muscarinic binding, phosphoinositide phosphorylation or subsequent hydrolysis by carbamoylcholine. The findings indicate the involvement of a GTP-binding protein in the coupling of the muscarinic receptor to phosphoinositide hydrolysis in the islet cell and suggest that this is distinct from the GTP-binding regulatory component of adenylate cyclase which is covalently modified by IAP. PMID- 2881541 TI - Effect of tryptic calmodulin fragments on guanylate cyclase activity from Paramecium tetraurelia. AB - Tryptic bovine brain calmodulin fragments 1-77 or 1-106 reactivated La inactivated ciliary guanylate cyclase from Paramecium dose-dependently up to 60%. They were 20-fold less potent compared to bovine brain calmodulin. Fragment 78 148 was even less active. Concomitant addition of fragments 1-77 and 78-148 had no additive effect. Genetically engineered calmodulin lacking a blocked amino terminus and trimethyllysine at position 115 reactivated La-treated guanylate cyclase as good as bovine brain calmodulin. After detergent solubilization of La inactivated guanylate cyclase intact bovine brain calmodulin and calmodulin fragments 1-77 and 78-148 were equipotent. 80% Reactivation was obtained with 40 microM of either fragment. PMID- 2881542 TI - Sulfated oligosaccharides in human lysosomal enzymes. AB - Cathepsin D, arylsulfatase A and the alpha-chain of beta-hexosaminidase are synthesized in human fibroblasts as sulfated polypeptides. The sulfate is added posttranslationally. Its half-life is less than one-tenth of that of the respective polypeptide chains. The sulfate residues were found on asparagine linked oligosaccharides sensitive to endoglycosidase F and peptide: N-glycosidase F and resistant to endoglycosidase H. Inhibition of formation of complex type oligosaccharides by 1-deoxy-manno-nojirimycin prevented sulfation, indicating that the sulfate residues were added to complex type oligosaccharides. PMID- 2881540 TI - Biosynthesis of intestinal microvillar proteins. Processing of N-linked carbohydrate is not required for surface expression. AB - Castanospermine, an inhibitor of glucosidase I, the initial enzyme in the trimming of N-linked carbohydrate, was used to study the importance of carbohydrate processing in the biosynthesis of microvillar enzymes in organ cultured pig intestinal explants. For aminopeptidase N (EC 3.4.11.2), aminopeptidase A (EC 3.4.11.7), sucrase-isomaltase (EC 3.2.1.48-10) and maltase glucoamylase (EC 3.2.1.20), castanospermine caused the formation of novel transient forms of higher Mr than corresponding controls, indicating a blocked removal of glucose residues. For the first three enzymes, the 'mature' (Golgi processed) forms were similar in size to or slightly smaller than corresponding controls and were, as shown for aminopeptidase N, endoglycosidase-H-sensitive, evidence of a blocked attachment of complex sugars. Maltase-glucoamylase did not undergo conversion into a 'mature' form, suggesting that, unlike other microvillar enzymes, it does not receive post-translational O-linked carbohydrate. Castanospermine suppressed the synthesis of the four enzymes, but did not block their transport to the microvillar membrane, showing that processing of N-linked carbohydrate is not required for microvillar expression. The proteinase inhibitor leupeptin partially restored the suppressed synthesis, indicating that the majority of the wrongly processed enzymes, probably because of conformational instability, become degraded soon after synthesis rather than being transported to the microvillar membrane. PMID- 2881543 TI - Human prepro atrial natriuretic factors 26-55, 56-92, and 104-123 increase renal guanylate cyclase activity. AB - Human prepro atrial natriuretic factors 26-55, 56-92, and 104-123 as well as human atrial natriuretic factor (4-28) in the present investigation increased renal cortical and medullary cyclic GMP levels and maximally enhanced particulate guanylate cyclase activity [E.C. 4.6.1.2] two-fold in whole kidney homogenates, renal cortical and medullary membranes, and in isolated distal nephrons at their 1 microM concentrations. Dose-response relationships revealed that the half maximal [ED50] activation of guanylate cyclase was at their 10 nM concentrations in rat, rabbit, and dog kidneys. Both human atrial natriuretic factor and the prepro factors decreased adenylate cyclase activity. These results suggest that prepro factors 26-55, 56-92, 104-123 may also be functionally active. PMID- 2881544 TI - Hydrogen peroxide elicits activation of bovine pulmonary arterial soluble guanylate cyclase by a mechanism associated with its metabolism by catalase. AB - Guanylate cyclase activity in the soluble extract of bovine pulmonary arteries is activated by hydrogen peroxide generated by glucose oxidase only in the presence of catalase. This mechanism of guanylate cyclase activation is not blocked by scavengers for superoxide anion or hydroxyl radical, but is selectively inhibited by methylene blue, inactivation of catalase and ethanol. The time dependency of increases in guanylate cyclase activity in the presence of peroxides that are substrates for catalase are associated with the spectral detection of compound I, a species of catalase formed during the metabolism of peroxide. Thus, activation of soluble guanylate cyclase appears to be elicited by compound I of catalase or by a mediator generated by this species. PMID- 2881545 TI - Effects of DJ-7141, a new alpha 2-adrenoceptor agonist, on catecholamine secretion from isolated bovine adrenal medullary cells. AB - The effects of a newly synthesized alpha 2-adrenoceptor agonist (an imidazole derivative, DJ-7141) on catecholamine secretion from isolated bovine adrenal medullary cells were examined. DJ-7141 did not affect basal catecholamine secretion, but inhibited catecholamine secretion induced by stimulation of the nicotinic ACh receptor. This inhibitory effect of DJ-7141 was less than that of clonidine, another alpha 2-agonist. DJ-7141 also inhibited [45Ca]2+ uptake by the cells induced by nicotinic stimulation. DJ-7141 did not affect catecholamine secretion induced by high K+ concentration. Its inhibitory effect on nicotine induced catecholamine secretion was not restored by increase in either the nicotine or Ca2+ concentration of the medium, suggesting that it interfered with the coupling between nicotinic ACh receptor stimulation and Ca2+-channel activation. The inhibitory effect of DJ-7141 seemed to be independent of its effect on alpha 2-adrenoceptors, because its effect was not antagonized by the alpha 2-adrenoceptor antagonists yohimbine and DG-5128, which both had no effect on either basal or nicotine-induced catecholamine secretion. PMID- 2881546 TI - REV 2871 (CHBZ): a potent antiallergic agent with a novel mechanism of action. II. Studies on the mechanism of action. AB - REV 2871 (CHBZ) was taken up by rat mast cells and human leukocytes in a specific and saturable manner. The compound can be hydrolyzed by a granule-associated enzyme in the mast cell to an ionic metabolite (REV 3579) whose in vitro profile is identical to that of disodium cromoglycate (DSCG). REV 3579, although achieving millimolar concentrations inside cells incubated with CHBZ, was not itself taken up by rat mast cells or human leukocytes. The unusual in vitro activity of CHBZ is postulated to arise from the fact that it is a prodrug for delivering a DSCG-like drug to the interior of a secretory cell. The internalized drug apparently exerts a more general and longer-lived inhibition of the secretory process than it can by acting on exterior membrane receptors. CHBZ thus represents a novel drug for studying anaphylactic responses in vitro. PMID- 2881547 TI - Effect of glutathione depletion by buthionine sulfoximine on rat embryonic development in vitro. AB - The intracellular thiol glutathione has many functions within cells including protection against xenobiotic and oxidative damage, and a role in protein and DNA synthesis and amino acid transport. Consequently, glutathione might be an important substance for normal growth and development. In this study the extent of glutathione depletion by buthionine sulfoximine, an agent which depletes glutathione by inhibiting its synthesis, and the subsequent effects of the depletion on rat embryonic growth and development were assessed. Day 10.5 rat embryos were cultured in rat serum medium in the presence of L-buthionine-S,R sulfoximine (0.01 to 2.0 mM) and examined for viability, malformations, growth and development 45 hr later. The glutathione concentrations of the cultured embryos and their yolk sacs were also determined. Exposure to buthionine sulfoximine produced marked and significant (P less than or equal to 0.05) depletion of glutathione at a buthionine sulfoximine concentration of 0.10 mM in the embryos and 0.05 mM in the yolk sacs. Exposure to 1 mM buthionine sulfoximine depleted glutathione to less than 7% of control in both of these tissues. None of the concentrations of buthionine sulfoximine tested had a significant effect on embryo viability; however, buthionine sulfoximine caused a significant (P less than or equal to 0.05) incidence of malformed embryos at concentrations of 0.25, 0.5, 1.0 and 2.0 mM. The types of defects induced by buthionine sulfoximine were blebs of the maxillary or nasal processes, prosencephalon or forelimb buds, small or misshapen heads, small prosencephalons and swollen hind brains, and tail defects. Embryonic growth was the most sensitive, of the variables assessed, to the effects of buthionine sulfoximine. Significant (P less than or equal to 0.05) growth retardation was observed at buthionine sulfoximine concentrations as low as 0.01 mM. At 2.0 mM buthionine sulfoximine, the yolk sac diameter, embryo crown rump length, head length, number of somites and morphological score were reduced to 65, 72, 77, 90 and 80% of control levels respectively. We propose that the embryotoxic effects of buthionine sulfoximine are due to glutathione depletion and, consequently, that a certain basal level of endogenous glutathione is essential to allow for normal development. PMID- 2881548 TI - Prizidilol. Metabolism by cytochrome P-450 and acetyltransferase. AB - The hepatic microsomal cytochrome P-450 enzyme system bound and metabolized the experimental drug prizidilol. Prizidilol bound to two distinct sites on cytochrome P-450. At low concentrations (less than ca 20 microM), prizidilol bound to the substrate binding site of the enzyme and produced a Type I difference spectrum. At higher concentrations (25-190 microM), prizidilol bound to the oxygen binding site of the enzyme and produced a type II difference spectrum. Prizidilol stimulated hepatic microsomal CO-inhibitable NADPH oxidation. Prizidilol metabolism by hepatic microsomes assessed by prizidilol disappearance was inhibited by CO:O2 (80:20; v/v), SKF 525-A and metyrapone. Prizidilol disappearance was monitored using a newly developed TLC assay for prizidilol following derivatization with quinolin-3-al. The apparent binding constants (Ks), maximum extents of binding (delta Amax), Michaelis constants (Km) and maximum velocities (Vmax) for the interaction of prizidilol with hepatic microsomal cytochrome P-450 were assessed in rats pretreated or not with the inducing agents phenobarbital, beta-naphthoflavone and pregnenolone-16 alpha carbonitrile. For the differently pretreated rats the apparent Ks values for the type I site and the type II site and the apparent Km were ca 3 microM, 150 microM and 2 microM, respectively. Apparent Vmax values varied from 20 to 70 pmol per min per mg microsomal protein. The observed effects of induction on the apparent equilibrium constants and maximum extents of binding and metabolism of prizidilol indicate that the forms of cytochrome P-450 induced by phenobarbital, pregnenolone-16 alpha-carbonitrile or beta-naphthoflavone do not play a major role in the metabolism of prizidilol. Prizidilol was also metabolized by hepatic cytosolic N-acetyltransferase. The apparent Km values for prizidilol and acetyl CoA were 0.8 and 22 microM. Apparent Vmax values were 50 and ca 2 pmol per min per mg protein for partially purified transferase and cytosol, respectively. It is concluded that the rates of oxidation and acetylation of this drug would be expected to be relatively low, being limited by low apparent Vmax values for both oxidation and acetylation. PMID- 2881550 TI - Restriction fragment length polymorphism for the T cell receptor alpha and beta chain genes in rheumatoid arthritis. PMID- 2881549 TI - In vitro and in vivo neurochemical effects of methylenedioxymethamphetamine on striatal monoaminergic systems in the rat brain. AB - A single high dose of methylenedioxymethamphetamine, a psychedelic agent, produced a rapid and persistent depletion of striatal indoles similar to that observed following administration of the serotonergic neurotoxin p chloroamphetamine. The drug had little effect on dopaminergic variables. Like p chloroamphetamine, methylenedioxymethamphetamine was found to be a relatively selective agent for inducing [3H]serotonin release in vitro. The serotonin uptake inhibitor, citalopram, blocked both [3H]serotonin release in vitro and striatal serotonin depletion in vivo, indicating that both processes were carrier dependent. In vivo comparisons of the stereoisomers of methylenedioxymethamphetamine indicated two phases of serotonin depletion similar to those reported for p-chloroamphetamine. Although both the (+)- and (-) stereoisomers produced an acute (3 hr) decrease in striatal indoles, the long term effects of the drug showed stereoselectivity in that the (+)-enantiomer produced the most dramatic serotonin depletion. Comparison of the effects of the stereoisomers of methylenedioxymethamphetamine and its n-desmethyl analog, methylenedioxyamphetamine, on [3H]serotonin and [3H]dopamine release in vitro showed the (+)-enantiomer of both drugs to be the more potent releasing agent. In spite of its reported lack of hallucinogenic activity, (+)methylenedioxyamphetamine was found to be of a potency similar to that of (+)methylenedioxymethamphetamine in inducing [3H]serotonin release in vitro. The results are discussed in terms of the neurochemical similarities between methylenedioxymethamphetamine and p-chloroamphetamine as well as the proposed role of serotonin release in the behavioral effects of methylenedioxymethamphetamine. PMID- 2881552 TI - Lymphotropic viruses, Epstein-Barr virus (EBV) and human T-cell lymphotropic virus-I (HTLV-I)/adult T-cell leukemia virus (ATLV), and HTLV-III/human immune deficiency virus (HIV) as etiological agents of malignant lymphoma and immune deficiency. AB - The ubiquitous, DNA herpesvirus, EBV, has B cell tropism and the geographically restricted RNA retrovirus, ATLV/HTLV-I has T cell tropism. Clinical descriptions by Burkitt and Takatsuki led to discovery of these viruses which infect silently early in life; however, ATLV is also transmitted to a spouse or by blood transfusion. In normal seropositive persons both viruses infect only 1 in about 10,000 B or T cells, respectively. EBV is associated with Burkitt's lymphoma, nasopharyngeal carcinoma, and infectious mononucleosis. ATLV is associated with adult T cell leukemia/lymphoma and smoldering T cell lymphoma. EBV infects polyclonally and is controlled by multiple cellular and humoral control mechanisms. Escape from immune surveillance as in immune deficient African children with malaria, males with x-linked lymphoproliferative syndrome, organ transplant recipients, and AIDS patients permits conversion from polyclonal to oligoclonal and finally, monoclonal malignancy. T cell immune defects permit proliferation of cells which undergo molecular and/or cytogenetic alterations. In contrast to EBV, which is integrated and nonintegrated in B cells, ATLV is monoclonally integrated. Viral transforming proteins and immune suppressive substances are produced. Immune deficiency in silent carriers of ATLV and in those with smoldering ATL suggest that immune surveillance deters emergence of ATL. Prevention of primary infection by vaccination against these lymphotropic viruses, and use of immunotherapy and antiviral drugs may potentially retard conversion of infected B or T cells to monoclonal malignancy. PMID- 2881551 TI - Toxicity of MDA (3,4-methylenedioxyamphetamine) considered for relevance to hazards of MDMA (Ecstasy) abuse. AB - Despite a paucity of data on its animal pharmacology and toxicology, MDMA [Ecstasy, XTC, ADAM; (+/-)-3,4-methylenedioxymethamphetamine] was introduced as an "underground" (FDA-unapproved) adjunct to psychotherapy in the late 1970's and early 1980's, in addition to its use as a recreational drug. Analysis of the limited experimental literature indicates that LD50's for MDMA in five species by several routes of administration tend to predict a significant human toxicity. MDMA was either equally toxic or slightly to moderately less toxic than its close congener, MDA, (+/-)-3,4-methylenedioxyamphetamine. It is suggested that extrapolation of the pharmacologic/toxicologic data available for MDA to MDMA should be assumed to be valid until disproven. Recently published canine data describe physiologic disturbances caused by acute overdosage of MDA, and also indicate the utility of chlorpromazine as an antidote preventing fatalities associated with severe hyperthermia, lactacidemia, hypertension and tachycardia. The toxicology of MDMA warrants further direct study in view of its continuing illegal distribution. PMID- 2881553 TI - Process of immortalization by Epstein-Barr virus and oncogenic conversion of the immortalized cells. AB - Transcription of Epstein Barr virus (EBV) genome during immortalization of tonsil lymphocytes was studied. Cytoplasmic poly(A) RNA was Northern blot hybridized with 32P-labeled cloned EBV fragments. A 5.1 kb band was detected by hybridization with BamHI-H, -F, -K, -A and het fragments. The implication of this finding is discussed. DNA obtained from cells established from a colony of immortalized tonsil lymphocytes in 0.4% soft agar was found to transform NIH 3T3 cells. The transformed cells were able to induce tumor in nude mice, although the originally established lymphocytes from the colony did not. This may indicate that a certain population of EBV immortalized cells may contain a potentially oncogenic gene which can function as an oncogene in NIH 3T3 cells. PMID- 2881554 TI - Transmission of adult T-cell leukemia virus (HTLV-I) through blood transfusion and its prevention. AB - Cell-associated transmission of adult T-cell leukemia virus (ATLV/HTLV-I) suggested early in a follow-up study on recipients of blood has been supported with the latest results of an extended follow-up. Approximately 10(8) lymphocytes of blood donors carrying the antibodies against ATLV seemed to be necessary for the infection through blood transfusion. The infection transmitted by transfusion is now almost completely prevented by eliminating blood units that have been derived from blood donors having antibodies to ATLV/HTLV-I. PMID- 2881555 TI - Seroepidemiology of adult T-cell leukemia virus (HTLV-I/ATLV): origin of virus carriers in Japan. AB - There are two large clusters of HTLV-I/ATLV carriers in the world. One large endemic area could be Africa, but available information is not yet sufficient to prove this. The other definitely large endemic area is Japan. Much smaller endemic areas and sporadic cases of the virus-carriers have been found in many parts of the world, including the Caribbean basin and Taiwan. Where did ATL virus carriers in Japan come from? From seroepidemiological studies, it is postulated that the carriers originated among Jomon people, who were the earliest inhabitants of Japan in 300 to 10,000 B.C. or earlier. PMID- 2881556 TI - Retroviral etiology of the acquired immune deficiency syndrome (AIDS). AB - The acquired immune deficiency syndrome (AIDS) is characterized by severe immunological defects resulting in opportunistic infections and malignancies. A novel human retrovirus, known under the terms of LAV, HTLV-III, ARV or as a human immunodeficiency virus (HIV), has been defined as the infectious agent responsible for the induction of the immunologic disorders in AIDS. However, two recent lines of evidence, reviewed in this article, complicate the etiological picture of AIDS: the HIV family appears to consist of a great number of diverse, and perhaps diversifying in vivo, members that exhibit different molecular and biological properties; the human retrovirus family may contain yet another distinct class of member viruses that resemble HIV morphologically and structurally but may differ in their pathogenicity. Our understanding of the retroviral etiology of AIDS may be far from complete. PMID- 2881557 TI - Structure of HTLV and its biological function in leukemogenesis of adult T-cell leukemia. AB - There is a high homology of nucleotide sequence between 3' two-thirds of the X (or pX) regions of human T-cell leukemia virus (HTLV)-I, and of HTLV-II. Monoclonal antibody against p41 coded from X-IV, an open reading frame of X region of HTLV-I, was established. Two proteins coded by Xb, one of the open reading frames in X region of HTLV-II, were newly identified as p24 and p26. The expression of X protein of HTLV-II in the reconstituted mouse embryonal carcinoma cell line, which shows myoblastic morphology, reverted the morphology to that of the original embryonal carcinoma cells. This suggests that the function of X protein is to disturb the regulation of cell lineage determination. Leukemogenesis of adult T-cell leukemia (ATL) is also considered to consist of multisteps, in which HTLV-I constitutes one step, other factors also being involved. Even the role of HTLV-I factor could be similarly played by other factor(s). In agreement with this hypothesis, there are patients with ATL without associated HTLV-I. PMID- 2881558 TI - [Molecular analysis of mitochondrial DNA of patients with mitochondrial cytopathy]. PMID- 2881559 TI - Receptor-mediated endocytosis: concepts emerging from the LDL receptor system. PMID- 2881560 TI - Generation of polarity during Caulobacter cell differentiation. PMID- 2881561 TI - Spatial programming of gene expression in early Drosophila embryogenesis. PMID- 2881563 TI - Oral sedation with temazepam: a practical alternative for use in dentistry? PMID- 2881562 TI - [Recent advances in biochemical studies of dementia in the elderly]. PMID- 2881564 TI - Adverse effects of opioid analgesic drugs. AB - Opioids were available in clinical practice since before the birth of modern anaesthesia--Seturner isolated morphine in 1806. They have a record of safety which is reflected in their high therapeutic ratios, especially the synthetic opioids introduced recently (table III). The most serious immediate adverse effect, respiratory depression, is a predictable effect related closely to analgesia. It is fortunate for anaesthetists who use opioids regularly, that recognition and treatment of respiratory problems are an integral part of their craft and that opioid antagonists are effective in reversing respiratory depression. PMID- 2881565 TI - Effects of atracurium and vecuronium on the latency and the duration of the negative deflection of the evoked compound action potential of the adductor pollicis. AB - The effect of atracurium or vecuronium on the depolarization phase of the evoked compound action potential of the adductor pollicis has been investigated in 30 adult patients. Patients were studied using single supramaximal stimulation of the ulnar nerve at the wrist. The evoked compound action potential was measured over the adductor pollicis muscle. When blockade by atracurium exceeded 80%, a significant decrease in latency was recorded (P less than 0.05). There was no significant change in latency after vecuronium. During the onset of blockade, depression of the amplitude of the evoked compound action potential was associated with a prolongation of its duration (P less than 0.05). The mean maximum increase in the negative deflection time was found to be similar after atracurium and after vecuronium. However, this phase was prolonged to a greater extent for a given degree of amplitude depression during the onset of blockade by atracurium (P less than 0.05). PMID- 2881566 TI - Changes in the power spectrum of the evoked compound action potential of the adductor pollicis with the onset of neuromuscular blockade. AB - The effects of neuromuscular blockade by atracurium and vecuronium on the power spectrum of the evoked compound action potential (ECAP) of the adductor pollicis were investigated in 30 adult patients undergoing elective surgery. The changes in amplitude and mean power frequency (MPF) of the ECAP were measured. Ten patients received an ED95 (0.23 mg kg-1) of atracurium and 10 received an ED95 (0.055 mg kg-1) of vecuronium. The remaining 10 patients did not receive any neuromuscular blocking drug, and were monitored for 6 min to exclude any time related changes in the ECAP. Neuromuscular blockade produced a decrease in total power and a shift towards lower frequencies. This was reflected in a decrease in the MPF in those patients receiving atracurium or vecuronium. There was no significant difference (P less than 0.05) between the atracurium and vecuronium groups in the magnitude of the change in MPF. These findings suggest that the previously reported increase in the duration of the negative deflection of the ECAP is predominantly the result of a change in its frequency components. PMID- 2881567 TI - Tubocurarine and pancuronium inhibit evoked release of acetylcholine from the mouse hemidiaphragm preparation. AB - Using a sensitive radioactive method that measures selectively the evoked release of acetylcholine, it was demonstrated that, when stimulating at 50 Hz, tubocurarine or pancuronium 2 X 10(-5) mol litre-1 or hexamethonium 10(-3) mol litre-1 significantly decreased the evoked release of acetylcholine in the mouse in vitro phrenic nerve-hemidiaphragm preparation. PMID- 2881568 TI - Haemodynamic effects of vecuronium, pancuronium and atracurium in patients with coronary artery disease. AB - Thirty patients with ischaemic heart disease scheduled for coronary artery bypass grafting were randomly allocated to three equal groups. Following morphine, hyoscine and pentobarbitone premedication, anaesthesia was induced with diazepam 0.3 mg kg-1. Five minutes later neuromuscular blockade was induced with pancuronium 0.1 mg kg-1, vecuronium 0.1 mg-1 or atracurium 0.5 mg kg-1, followed after 6 min by fentanyl 25 micrograms kg-1. Pancuronium and atracurium caused significant increases in heart rate, while vecuronium induced little change. Systemic vascular resistance decreased significantly from 1515 dyn s cm-5 to 1200 dyn s cm-5 following atracurium. Cardiac index was increased transiently in the atracurium group, but a more sustained increase was observed following pancuronium. Nine patients in the atracurium group showed skin flushing and one developed skin weals. PMID- 2881569 TI - Alcohol and alcohol problems research 13. U.S.S.R. PMID- 2881570 TI - Khat: scientific knowledge and policy issues. PMID- 2881571 TI - Alcohol use among khat (Catha) chewers in Kenya. PMID- 2881572 TI - The respiratory effects of oral ethyl loflazepate in volunteers. AB - A volunteer study was undertaken to assess the respiratory effects of ethyl loflazepate, a new benzodiazepine, and to correlate these with plasma concentrations of the active metabolites. Twelve volunteers were given placebo, 2 mg ethyl loflazepate, and 6 mg ethyl loflazepate on separate occasions. Respiration and plasma metabolite levels were assessed hourly for 8 h and at 24 h. The 6 mg ethyl loflazepate treatment produced a significant decrease (P less than 0.02) in the ventilatory response to carbon dioxide at 5 h. However this did not equate with a peak in plasma metabolite concentrations which were maintained at a plateau level from 4 to 24 h. PMID- 2881573 TI - Differential effects of the anxiolytic drugs, diazepam and buspirone, on memory function. AB - The effects of the anxiolytic drugs diazepam (5 mg) or buspirone (5 or 10 mg) were studied in comparison with placebo on memory function in 39 subjects diagnosed with generalized anxiety disorder. Neither drug altered the immediate recall of a list of 16 nouns or impaired digit span, a second test of immediate memory. Diazepam selectively impaired the recall of nouns after a 20 min delay when compared with placebo. In contrast, neither dose of buspirone altered the delayed recall of the word list. The implications of such different effects of anxiolytic drugs on memory function for the clinical treatment of anxiety are discussed. PMID- 2881574 TI - Acute and subchronic effects of Org 2305 and diazepam on psychomotor performance in man. AB - Three doses (15, 30 and 60 mg) of Org 2305 (O 15, O 30 and O 60 respectively), a novel anxiolytic drug chemically related to mianserin, were compared with placebo and 15 mg diazepam (DZ) on human psychomotor performance in a double-blind, cross over study with 15 healthy volunteers. Objective measurements (choice reaction, tracking, flicker fusion, Maddox wing, digit symbol substitution, memory recall) and subjective assessments (visual analogue scales) were done at baseline and 2 and 13 h after the first dose. This testing procedure was repeated on day 7 when administering the seventh consecutive daily night-time dose. After the first dose O 15 did not differ from placebo and O 30 rarely differed from placebo. O 60 impaired various objective functions similarly to, or less than DZ. Subjectively, DZ and O 60 were felt as sedative. During subchronic treatment, DZ caused some impairment of baseline due to accumulation of bioassayable benzodiazepines, but significant responses to the last DZ dose were less than those to the first dose. DZ but not O 60 was reported to have caused lethargy and clumsiness during subchronic treatment. In the doses used Org 2305 impaired psychomotor performance less than diazepam did. A dose of 60 mg Org 2305 may offer some advantage over 15 mg diazepam, provided that their anxiolytic effects are about similar. PMID- 2881575 TI - The effect of topical dimethindene maleate on weal reactions. AB - The topical effect of the histamine H1-receptor antagonist dimethindene maleate on the wealing response to intradermal histamine, compound 48/80 and house dust mite antigen was studied in 16 subjects using a double-blind procedure. The mean reduction in weal area +/- s.e. mean was 44% +/- 13%, 43% +/- 13% and 31% +/- 13% for histamine, 48/80 and antigen respectively. We conclude that dimethindene maleate is a moderately potent H1-receptor antagonist, and that the inhibition of the 48/80 and house dust mite induced weals is accounted for by the antihistaminic effect of dimethindene maleate. PMID- 2881576 TI - Ligand binding studies of the F1 moiety of rat liver ATP synthase: implications about the enzyme's structure and mechanism. AB - F1-ATPase of rat liver was examined for its capacity to interact with both metal ions and nucleotides and for the effect of covalent ATPase inhibitors on these interactions. As isolated, rat liver F1 contains about 2 mol of Mg2+/mol of F1, 1 mol of which can be removed or exchanged. The remaining mole of Mg2+ per mole of F1 remains very tightly associated with F1 and is recovered in the alpha gamma fraction after cold denaturation. Rat liver F1 also contains as isolated a nearly equivalent amount of nucleotide (approximately 1.7 mol/mol of F1) which is readily removed by incubation at room temperature followed by column centrifugation. The "2 Mg2+ enzyme" binds almost 3 mol of 5'-adenylyl imidodiphosphate (AMP-PNP)/mol of F1 in the presence or absence of added divalent cation. When divalent cation is present as Co2+, an equivalent activator to Mg2+ in the ATPase reaction, 1 mol of F1 binds 3 mol of both AMP-PNP and Co2+. under these conditions, the very tight Mg2+ site remains loaded, the exchangeable Mg2+ site is replaced with AMP-PNPCo, and two additional AMP-PNPCo sites are filled. At this point, ADP can be loaded onto the enzyme as a fourth nucleotide at a site separate and distinct from the AMP-PNP sites. Significantly, rat liver F1 contains only a single readily detectable ADP binding site in the presence or absence of divalent cation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881577 TI - Inhibition of protein cross-linking in Ca2+-enriched human erythrocytes and activated platelets. AB - Treatment of human erythrocytes with Ca2+, in the presence of ionophore A23187, causes the formation of high molecular weight (greater than 10(6)) membrane protein polymers. This phenomenon, known to involve cross-linking of essentially all of the band 4.1 and 2.1 (ankyrin) proteins, as well as some spectrin, band 3, and hemoglobin molecules, could be prevented by preincubating the cells with a noncompetitive inhibitor of intrinsic transglutaminase, 2-[3 (diallylamino)propionyl]benzothiophene, at concentrations of about (3-6) X 10(-4) M. The compound also eliminated the proteolytic breakdown of the two major transmembrane proteins band 3 and glycophorin, which would otherwise occur during the Ca2+ loading of fresh human red cells. In addition, the inhibitor effectively blocked the formation of a cross-linked protein polymer in thrombin-activated human platelets. PMID- 2881578 TI - Interaction between the oligomycin sensitivity conferring protein and the F0 sector of the mitochondrial adenosinetriphosphatase complex: cooperative effect of the F1 sector. AB - Beef heart mitchondrial oligomycin sensitivity conferring protein (OSCP) labeled with [14C]-N-ethylmaleimide ([14C]OSCP) at the only cysteine residue, Cys-118, present in the sequence [Ovchinnikov, Y. A., Modyanov, N. N., Grinkevich, V. A., Aldanova, N. A., Trubetskaya, O. E., Nazimov, I.V., Hundal, T., & Ernster, L. (1984) FEBS Lett. 166, 19-22] exhibits full biological activity in a reconstituted F0-F1 system [Dupuis, A., Issartel, J. P., Lunardi, J., Satre, M., & Vignais, P. V. (1985) Biochemistry 24, 728-733]. The binding parameters of [14C]OSCP with respect to the F0 sector of submitochondrial particles largely depleted of F1 and OSCP (AUA particles) have been explored. In the absence of added F1, a limited number of high-affinity OSCP binding sites were detected in the AUA particles (20-40 pmol/mg of particles); under these conditions, the low affinity binding sites for OSCP were essentially not saturable. Addition of F1 to the particles promoted high-affinity binding for OSCP, with an apparent Kd of 5 nM, a value 16 times lower than the Kd relative to the binding of OSCP to F1 in the absence of particles. Saturation of the F1 and OSCP binding sites of AUA particles was attained with about 200 pmol of both F1 and OSCP added per milligram of particles. The oligomycin-dependent inhibition of F1-ATPase bound to AUA particles was assayed as a function of bound OSCP. At subsaturating concentrations of F1, the dose-effect curves were rectilinear until inhibition of ATPase activity by oligomycin was virtually complete, and maximal inhibition was obtained for an OSCP to F1 ratio of 1 (mol/mol).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881579 TI - Effects of glucocorticoid and thyroid hormones on regulatory enzymes of fatty acid synthesis and glycogen metabolism in developing fetal rat lung. AB - Although glucocorticoid and thyroid hormones are known to act synergistically to stimulate surfactant production, they have opposite effects on other parameters of fetal lung maturation. We recently reported that the developmental increases in de novo fatty acid synthesis and glycogen accumulation in fetal rat lung were accelerated by dexamethasone but prevented by triiodothyronine and that the dexamethasone-induced increases were diminished when the two hormones were administered together. We have now examined the effects of maternal administration of these hormones on activities of enzymes of lung fatty acid synthesis and glycogen metabolism in the rat. There was a developmental increase in fatty-acid synthase activity between 19 and 21 days gestation. This activity was increased by dexamethasone but decreased by triiodothyronine. When the two hormones were administered together the stimulatory effect of dexamethasone was decreased from 56% to 29%. The stimulatory effect on fatty-acid synthase was also observed in fetal lung explants cultured in the presence of dexamethasone. This shows that the effect of the hormone was directly on the fetal lung. Dexamethasone had no effect on liver fatty-acid synthase. There was a developmental decrease in acetyl-CoA carboxylase activity but it was not affected by the hormones. These data show that the developmental and hormone-induced changes in fetal lung de novo fatty acid synthesis are mediated by fatty-acid synthase. Although there were developmental changes in fetal lung 6 phosphofructokinase, glycogen synthase and glycogen phosphorylase activities, these enzymes were not affected by the hormones. PMID- 2881580 TI - Inhibition of purified bovine milk lipoprotein lipase by propranolol and other beta-adrenergic blockers in vitro. AB - Numerous clinical studies have shown that propranolol administration causes hypertriglyceridemia and a decrease in high-density lipoprotein in man. Although these findings have been attributed to diminution of triacylglycerol-rich lipoprotein catabolism by lipoprotein lipase, biochemical studies of the effects of propranolol on lipoprotein lipase activity in vitro have not been previously reported. We purified lipoprotein lipase from raw bovine skimmed milk and examined the effect of propranolol using as substrate phospholipid-stabilized, triolein emulsions containing purified human apolipoprotein C-II. These studies demonstrate that propranolol inhibits lipoprotein lipase activity. The inhibition was found to be noncompetitive with a Ki for propranolol of 0.55 mM. In addition, propranolol was shown to bind to phospholipid-stabilized triolein emulsions reaching local concentrations at the particle surface many times higher than its bulk concentration. Metoprolol, timolol and practolol, which are less hydrophobic than propranolol, were less inhibitory. Atenolol was the weakest inhibitor of purified bovine lipoprotein lipase in vitro. PMID- 2881581 TI - Induction of cellular transglutaminase biosynthesis by sodium butyrate. AB - Cellular transglutaminase activity was induced in simian virus-transformed human embryonic lung fibroblasts (WI-38 VA13A) by sodium butyrate. The level of enzyme activity approached a maximum by 6 days; 9-11-fold higher in the presence of sodium butyrate (1 mM) than in its absence. The observed increases in cellular transglutaminase activity could be entirely accounted for by equivalent increases in the levels of enzyme protein measured by inhibition enzyme-linked immunosorbent assay. Sodium butyrate also increased the rate of enzyme synthesis, but had no effect on the rate of cellular transglutaminase degradation. The increase in the rate of enzyme synthesis was matched by an increased level of translatable transglutaminase mRNA as measured in a cell-free translation system. Our results suggest that sodium butyrate regulates cellular transglutaminase at the pretranslational level. PMID- 2881582 TI - Adaptations of neurotransmitter synthesis to chronic hypoxia in cell culture. AB - Tyrosine hydroxylase and tryptophan hydroxylase are widely held to be rate limiting for the synthesis of the catecholamines and serotonin, respectively. Both enzymes are oxygen-requiring and kinetic properties suggest that oxygen availability may limit synthesis of these neurotransmitters in the brain. Using pheochromocytoma cells as a cell culture model for catecholamine synthesis, and neuroblastoma cells as a model for serotonin synthesis, enzyme activity was measured under control and hypoxic conditions. Both tyrosine hydroxylase and tryptophan hydroxylase activity increased substantially with chronic exposure but not with acute exposure. In the case of tyrosine hydroxylase, increased enzyme content with hypoxia accounts for increased activity. This suggests a mechanism for the maintenance of neurotransmitter synthesis with chronic hypoxia. Measurement of intracellular metabolites revealed no change in dopamine or norepinephrine in hypoxic pheochromocytoma cells, consistent with a simple adaptive mechanism. However, in neuroblastoma cells, hypoxia was associated with an increase in serotonin concentration. The reasons for this are still unclear. PMID- 2881583 TI - Regulation of intestinal mucosa guanylate cyclase by hemin, heme and protoporphyrin IX. AB - Mg2+-dependent activity of intestinal brush border guanylate cyclase was stimulated 4-5-fold by 50-100 microM hemin. Higher concentrations were inhibitory. In the presence of 25% dimethyl sulfoxide, which stimulated activity 9-times, 50 microM hemin further increased activity 1.7-fold. However, when activity was stimulated 32-fold by the Escherichia coli heat-stable enterotoxin, or 26-fold by Lubrol PX, hemin produced only concentration-dependent inhibition. The first type of activation was more sensitive to hemin than the second. Reduction of hemin by dithiothreitol eliminated stimulation of basal activity, while inhibition of Lubrol PX-stimulated activity remained. Protoporphyrin IX also had no effect on basal activity, however, it inhibited enterotoxin- and Lubrol PX-stimulated activities similarly, but only to half the extent of hemin. Substitution of Mn2+ for Mg2+ elevated basal activity 15-fold, and this Mn2+ dependent activity was inhibited by hemin. Mn2+-dependent activity was stimulated (43%) by enterotoxin, however, the stimulated activity was more sensitive to hemin inhibition than the basal Mn2+-dependent activity and both inhibition curves were congruent above 50 microM hemin. Hemin inhibition of Lubrol PX stimulated activity was much less with Mn2+ than with Mg2+. These results were interpreted as suggesting two sites of hemin inhibition; on an inhibitory regulator and on the enzyme. We also found that the secretory effect of enterotoxin in the suckling mouse bioassay was reduced 56% by the oral administration of hemin. PMID- 2881584 TI - Receptor-mediated responses of plasma membranes isolated from Lytechinus pictus spermatozoa. AB - Speract (Gly-Phe-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly), a peptide obtained from eggs, has been shown to bind to a plasma membrane receptor of Lytechinus pictus spermatozoa. Here, we show that the addition of speract to intact cells caused the appearance of a new protein-staining band (Mr = 140,000) on sodium dodecyl sulfate (SDS) polyacrylamide gels; concomitantly, a protein of apparent molecular weight (Mr) 150,000 disappeared. Guanylate cyclase activity also decreased approximately 50% after the addition of speract to intact cells. Plasma membranes were subsequently prepared from spermatozoa in the presence of fluoride at pH 6.0, conditions that resulted in retention of the speract receptor and the Mr 150,000 protein. Addition of speract to the membranes resulted in a disappearance of the Mr 150,000 protein and the appearance of a Mr 140,000 protein. Coincident with the apparent change in molecular weight, guanylate cyclase activity decreased 30% at maximal speract concentrations. A physiological event that occurs in the intact cell in response to speract can now be reproduced in isolated plasma membranes; it should, therefore, now be possible to define the molecular events that occur as a result of speract: receptor interaction. PMID- 2881585 TI - [Significance of the dopamine-blocking and m-choline-blocking components in the antiapomorphine action of neuroleptics]. AB - In experiments on rats and mice the correlation between the ability of neuroleptics to antagonize apomorphine induced stereotypy and to block central dopamine and muscarinic acetylcholine receptors was studied. The analysis showed significant correlation (v = 0.76; P less than 0.05) between antistereotypic effects of drugs and their ability to inhibit 3H-spiperone binding to rat striated tissue. However, no correlation was found between antistereotypic effect of neuroleptics and their ability to block 3H-quinuclidinyl benzylate binding or arecoline-induced tremor. PMID- 2881586 TI - [Modelling of malignant lymphoma in rabbits using primate oncogenic viruses. Preliminary report]. AB - Inoculation of rabbits with permanent B-cell line cultures obtained from Stumptailed Macaques M. arctoides (MAL) which contain lymphotropic herpesvirus and C-type particles has led to the development of generalized lymphomas. The lymphoma cells had rabbit karyotype and did not contain surface an cytoplasmic immunoglobulins. Permanent suspension of lymphoid cell line independent of growth factors was obtained from rabbit lymphoma. The serum of a rabbit with lymphoma transmitted from another rabbit with MAL-induced lymphoma did not react with virus-negative human Raji cells when tested in immunofluorescence. But this serum reacted positively with cytoplasmic antigens of simian 594S-F9 cells (producing lymphotropic herpesvirus and two types of retroviruses, namely, endogenous C-type and HTLV-I-like) and human C91-PL cells (producing HTLV-I). The results obtained demonstrated high oncogenicity of the viruses produced by simian permanent cellular MAL lines for rabbits. PMID- 2881587 TI - Increased susceptibility of peripheral mononuclear cells of leukemic patients to HTLV-I infection in vitro. AB - Peripheral mononuclear cells (MNC) collected from 12 healthy donors and 44 leukemic patients at various stages of the disease were tested for natural killer (NK) activity and for their susceptibility to HTLV-I infection in vitro, measured in terms of percentage of p19 positive cells. MNC from leukemic donors at any stage of leukemia (ie, onset or relapse, ON/REL; complete remission or off therapy, CR/OT donors) were highly susceptible to HTLV-I infection. This was true for acute leukemias of lymphoblastic (ALL) or nonlymphoblastic (ANLL) type. MNC of ON/REL patients were more susceptible to HTLV-I than those of CR/OT donors. In addition, leukemic blasts were more rapidly infected (ie, within five to seven days) than the HTLV-I-susceptible normal cord-blood lymphocytes. However, the presence of circulating blasts was not essential to virus susceptibility, since CR/OT MNC, presumably free of leukemic blasts, were still more susceptible to HTLV-I than normal cells. Basal NK function of MNC from leukemic patients was significantly lower than that detectable in healthy controls. However, no correlation was found between susceptibility to HTLV-I infection and NK activity. PMID- 2881588 TI - Mother-to-offspring transmission of human T cell leukemia virus type I in rabbits. AB - We studied the mode of natural transmission of human T-cell leukemia virus type I (HTLV-I) in rabbits. Four virus-infected rabbits (2 males and 2 females) were individually mated with 4 noninfected rabbits. Two virus-infected females mated with noninfected males gave birth to 7 offspring, and 2 noninfected females mated with infected males delivered 5 offspring. Four of the seven offspring born to the virus-infected mothers seroconverted for HTLV-I when aged 6 to 13 weeks with antibody titers of 1:40 to 1:160. None of the five offspring born to the noninfected mothers became seropositive during the observation period of 6 months, however. Peripheral lymphocytes were cultured with T cell growth factor, and HTLV-I-carrying lymphoid cell lines were established from the four seroconverted rabbits. All four cell lines were of T cells positive for Ia antigens. In addition, none of five newborn rabbits killed immediately after birth to a virus-infected rabbit was infected with HTLV-I. These findings provide an experimental support for the milkborne transmission of HTLV-I from mother to child in humans and indicate that the virus is tropic for T cells in rabbits as well. PMID- 2881589 TI - Chromosome aberrations and clinical features of adult T cell leukemia-lymphoma not associated with human T cell leukemia virus type I. AB - Chromosome aberrations and clinical features of three patients with adult T cell leukemia-lymphoma (ATL) not associated with human T cell leukemia virus type I (HTLV-I) are described. From their clinical features, two patients were diagnosed as acute type and one patient was diagnosed as chronic type, which later converted to acute crisis. Clonal and many chromosomal abnormalities were observed before therapy in the two acute type cases and at relapse in the chronic type case. Karyotype aberrations, including trisomy 3, trisomy 7, trisomy 21, del(6)(q21), del(10)(p13), 14q11 translocation, and loss of X chromosome, all of which are frequently found in HTLV-I associated ATL, were also seen in these cases of HTLV-I-negative ATL. PMID- 2881591 TI - Polyarteritis nodosa and familial Mediterranean fever. AB - A 22-year-old familial Mediterranean fever (FMF) patient was hospitalized for continuous fever, myalgia, hypertension, vertigo and a petechial rash. Laboratory findings revealed hyperglobulinaemia, thrombocytosis and a leukaemoid reaction. While on steroid therapy the patient sustained a haemorrhage into a renal aneurysm which responded to gel foam embolization. After 12 months of follow-up his condition remained stable under treatment with cyclophosphamide, prednisone and antihypertensive medications. This case provides the fourth example of polyarteritis nodosa associated with FMF. PMID- 2881592 TI - GRF neurons in the rat hypothalamus. AB - The growth hormone-releasing factor (GRF)-containing neuronal system was immunohistochemically studied in the rat hypothalamus. The immunolabeled cell bodies were determined by intraventricular administration of colchicine 24 h before killing. In intact animals, the neurons appeared in the ventral portion of the arcuate nucleus (group 1) and in the area surrounding the ventromedial nucleus (group 2). Most of the cell bodies also indicated immunoreactivity for tyrosine hydroxylase (TH). The immunoreactive fibers accumulated showing a palisade arrangement in the external layer of the median eminence. The rats treated neonatally with monosodium glutamate revealed group 2 neurons and a few immunoreactive fibers in the median eminence. Half-anterolateral deafferentation of the medial basal hypothalamus, which was performed to isolate group 1 neurons or both group 1 and 2 neurons from the other brain parts, did not remarkably affect the appearance of the fibers in the median eminence. However, the perikarya were hypertrophic and strongly immunolabeled for GRF and TH. It is concluded that the fibers containing GRF in the median eminence derive mostly from group 1 neurons, and that the neurons may be regulated by an inhibitory mechanism by other neurons on the outside of the deafferented hypothalamic islands. GRF synthesized in group 2 neurons may act on other neurons as a neurotransmitter-like substance. PMID- 2881590 TI - Effect of exogenous 5,8,11,14,17-eicosapentaenoic acid on cardiac anaphylaxis. AB - The effects of infusions of eicosapentaenoic acid (EPA) (6 X 10(-8) mol min-1 and 15 X 10(-8) mol min-1) on the coronary constriction and the release of immunoreactive sulphidopeptide-leukotrienes (SP-LT), thromboxane B2(TXB2) and 6 keto-prostaglandin F1 alpha (PGF1 alpha) from perfused anaphylactic guinea-pig hearts were investigated. EPA dose-dependently inhibited the profound early coronary flow reduction after antigen injection. The less pronounced late phase of anaphylactic coronary flow reduction was, however, not significantly affected. EPA (15 X 10(-8) mol min-1) significantly shortened the average duration of antigen-induced arrhythmias. EPA dose-dependently decreased release of immunoreactive TXB2 and 6-keto-PGF1 alpha from anaphylactic guinea-pig hearts. Release of immunoreactive SP-LT was dose-dependently increased after antigen challenge in the presence of EPA. Inhibiton of the release of SP-LT by the lipoxygenase inhibitor esculetin (1 X 10(-7) mol min-1) was accompanied by a significant attenuation of flow reduction during the late phase of anaphylactic vasoconstriction. Reversed phase h.p.l.c. of perfusates from anaphylactic guinea pig hearts revealed immunoreactivity comigrating with authentic leukotriene C4 (LTC4), LTD4, and LTE4. In perfusates from hearts treated with EPA infusions, additional immunoreactivity was detected comigrating with LTC5, LTD5 and LTE5. In addition to immunoreactivity migrating with LTB4, as observed in control heart perfusates, in perfusates from EPA-treated hearts, a second peak was observed, which coincides with the retention time described for LTB5. Exogenous LTC5 (1 X 10(-12) mol min-1 and 20 X 10(-12) mol min-1) induced dose-dependent reductions of coronary flow and was found to be a slightly weaker constrictor than LTC4, but no significant differences were observed. Coronary vasoconstriction elicited by infusion of exogenous LTC4 (20 X 10(-12) mol min-1) was dose-dependently inhibited by infusions of EPA. However, the negative inotropic effect of LTC4 remained unaffected. Thus, in the isolated anaphylactic heart of the guinea-pig exogenous EPA was effectively metabolized via the 5-lipoxygenase pathway whereas the cyclo-oxygenase pathway of polyunsaturated fatty acid metabolism was found to be inhibited. The results are in agreement with the suggestion that cyclo oxygenase products are mediators of the early phase of the anaphylactic coronary constriction, while vasoconstrictor SP-LT are involved in the later phase. However, in spite of enhanced release of SP-LT, EPA infusion did not result in increased coronary constriction. Considering the fact that EPA antagonizes LTC4 induced coronary constriction, it seems possible, that EPA might act as a functional antagonist of vasoconstrictor eicosanoids including EPA-derived SP-LT. PMID- 2881593 TI - Catecholamine innervation of LH-RH neurons: a developmental study. AB - Catecholamine innervation of luteinizing hormone-releasing hormone (LH-RH) cell subtypes in rats was investigated over development using double label, light microscopic immunocytochemistry. Similar results were observed in both sexes. The number of catecholamine-apposed sLH-RH cells remained constant, while the number of catecholamine-apposed iLH-RH cells increased as a function of age. These results suggest that LH-RH cell subtypes are differentially innervated and support the hypothesis that the development of iLH-RH cells represent newly innervated surfaces which are related to changes in the processing of incoming information relevant to reproductive maturation. PMID- 2881594 TI - Evidence that the cultured multipolar neurons of the lower brainstem of SHR and WKY rats differ significantly in the mode of responses to catecholamines. AB - By using cultures of 6 types of dissociated neurons from the lower brainstem of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, we analyzed differences in the mode of response of the cultured neurons to 9 kinds of peptides and 7 kinds of neurotransmitters, and obtained evidence that there is a significant difference in the mode of response of multipolar neurons to catecholamines; dominantly facilitation in SHR, but dominantly inhibition in WKY rats. PMID- 2881596 TI - Acromelic acid, a novel excitatory amino acid from a poisonous mushroom: effects on the crayfish neuromuscular junction. AB - A novel amino acid, acromelic acid, which is one of kainoids isolated from a poisonous mushroom, markedly depolarizes the crayfish opener muscle fiber in a dose-dependent manner, its potency being much greater than that of kainoids such as kainic or domoic acid. Moreover, acrolemic acid markedly potentiates the glutamate response, in spite of the fact that it reduces the quisqualate response in a dose-dependent manner. The amplitude of excitatory junctional potentials was slightly reduced by acromelic acid. PMID- 2881595 TI - GABA-gated chloride ion influx and receptor binding studies in C57BL6J and DBA2J mice. AB - GABA-gated chloride ion influx was measured in brain 'microsac' preparations of young (20-22-day-old) and older (40-42-day-old) C57BL6J and DBA2J mice. The young DBA2J mice are susceptible to audiogenic seizures. GABA sensitivity was reduced in young DBA2J mice as compared to age-matched C57BL6J mice or older mice of either strain. Age and strain differences in ligand binding to GABA/benzodiazepine receptor complex and glutamate receptor could not account for this finding. These results provide evidence for a defect in GABA-gated chloride ion influx in audiogenic seizure-susceptible DBA2J mice. PMID- 2881597 TI - Increased in vivo tyrosine hydroxylase activity in rat telencephalon produced by self-stimulation of the ventral tegmental area. AB - Changes in the activity of dopaminergic neurons associated with intracranial self stimulation of the ventral tegmentum were assessed by measuring the accumulation of 3,4-dihydroxyphenylalanine (DOPA) after inhibition of aromatic amino acid decarboxylase by NSD-1015. When compared to implanted unstimulated controls, DOPA concentrations were elevated significantly in the nucleus accumbens, striatum and olfactory tubercle in the hemisphere ipsilateral to the electrode, after a 30 min session of self-stimulation. The concentration of DOPA in the contralateral nucleus accumbens and striatum did not differ from control levels, although relative to control values it was significantly increased in the contralateral olfactory tubercle. A similar analysis of in vivo tyrosine hydroxylase activity in these brain regions following a 30 min session of lever pressing for food reward on a fixed-ratio (FR-8) schedule failed to reveal any significant changes relative to control subjects. These results are consistent with a role for dopamine in brain-stimulation reward obtained from electrical stimulation of the ventral tegmental area but do not provide evidence for dopaminergic mediation of the rewarding properties of food. PMID- 2881598 TI - Multiple Cl(-)-independent binding sites for the excitatory amino acids: glutamate, aspartate and cysteine sulfinate in rat brain membranes. AB - As we have recently reported that Cl(-)-dependent glutamate (GLU) binding reflects GLU accumulation into membrane vesicles, the characteristics, kinetics and pharmacological specificities of L-[3H]glutamate (L-[3H]GLU) binding to crude rat brain synaptic membranes, were investigated in Cl(-)-free medium. L-[3H]GLU binding was systematically compared to that of L-[3H]cysteine sulfinate (L [3H]CSA) and L-[3H]ASP), two other putative excitatory amino acids. A high affinity site was determined for each of these radioactive ligands (L-[3H]GLU: Kd = 0.14 microM, Bm = 3.4 pmol/mg protein; L-[3H]CSA: Kd = 0.07 microM, Bm = 2.2 pmol/mg protein; L-[3H]ASP: Kd = 5.8 microM, Bm = 31.2 pmol/mg protein). The pharmacological specificity of these Cl(-)-independent binding sites indicate the existence of at least 3 distinct high affinity sites, all different from the Cl( )-dependent GLU binding 'site': one having a similar affinity for GLU and CSA, a second one preferring CSA, and a third one preferring ASP. Among the large quantity of structural analogs of the neuroexcitatory amino acids tested, only endogenous compounds (GLU, ASP and CSA) (except hydroxylamine-o-sulfate) were able to interact efficiently. No inhibition by classical agonists and antagonists (such as N-methyl-D-aspartate, quisqualate, kainate, 2-amino-4-phosphonobutyrate, or 2-amino-5-phosphonovalerate) was found. In addition to their high specificity, these Cl(-)-independent sites possess most other biochemical characteristics of receptor proteins. PMID- 2881600 TI - Spinal antinociceptive action of three representative opioid peptides in frogs. AB - Spinal administration of low doses of dynorphin, beta-endorphin or Met-enkephalin produces a potent, dose-dependent increase in the nociceptive threshold in the unanesthetized frog, Rana pipiens. Nociceptive thresholds were determined by using the acetic acid test, previously shown to be a sensitive indicator of antinociception in this amphibian species. Of particular interest, spinally administered dynorphin produces a potent antinociception in frogs without any signs of motor dysfunction seen after spinally administered dynorphin in mammalian species. PMID- 2881599 TI - Immunocytochemical localizations of cytosolic and mitochondrial glutamic oxaloacetic transaminase isozymes in rat primary sensory neurons as a marker for the glutamate neuronal system. AB - The localization of cytosolic (s-) and mitochondrial (m-) glutamic oxaloacetic transaminase (GOT) was examined in the rat trigeminal, jugular and dorsal root ganglia by means of an indirect immunofluorescence method using antibodies specific for s- and m-GOT. Staining of s-GOT-like immunoreactivity was seen in giant, large, medium and small cells in these ganglia. On the other hand, m-GOT like immunoreactivity was not seen in them. The distribution of GOT suggests that glutamate may be a transmitter released from primary sensory neurons. PMID- 2881601 TI - [3H]AMPA binding to glutamate receptor subpopulations in rat brain. AB - The glutamate analog (RS)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA), displaced 11% of the binding of L-[3H]glutamate to rat brain membranes, amounting to 22% of the specific binding displaceable by excess non radioactive glutamate. AMPA-sensitive L-[3H]glutamate binding was additive with that displaced by kainic acid (1 microM) plus N-methyl-D-aspartate (10 microM) when low concentrations of non-radioactive AMPA (1 microM) were employed to determine non-specific background, but partially overlapped when higher concentration of AMPA (100 microM) were used. [3H]AMPA binding was 21% specific (displaceable by non-radioactive 0.1 mM AMPA) in sodium-, calcium- and chloride free buffer, but increased to over 30% in the presence of 0.1 M chloride. AMPA sensitive glutamate binding and AMPA binding were both stimulated dramatically by thiocyanate and by several other anions. [3H]AMPA binding activity was resistant to freezing and thawing, optimal at 0-4 degrees C, and detectable at slightly reduced levels by filtration assays and in tissue section autoradiography. AMPA showed a heterogeneous affinity in displacement of L-[3H]glutamate, and [3H]AMPA binding showed heterogeneity with respect to AMPA, quisqualate, and glutamic acid diethyl ester. Scatchard plots gave a best fit for two sites with Kd values of 28 and 500 nM and Bmax values of 200 and 1800 fmol/mg protein, respectively. [3H]AMPA was inhibited by quisqualate (IC50 = 60 nM), L-glutamate (2 microM), (RS)-3-hydroxy-4,5,6,7-tetrahydroisoxazolo-[5,4-c]-pyridine-7-carboxylic acid (7 HPCA, 5 microM), kainic acid (20 microM) and glutamic acid diethyl ester (21 microM) but insensitive to L-aspartate, ibotenic acid, N-methyl-D-aspartate, (RS) 2-amino-phosphonobutyric acid and (RS)-2-amino-phosphonovaleric acid. This is consistent with labeling of a quisqualate-specific subpopulation of glutamate receptors. The high affinity (28 nM) and intermediate affinity (0.5 microM) AMPA sites had similar pharmacological specificity and brain regional distribution as determined by autoradiography. The latter revealed high densities of [3H]AMPA binding in the superficial layers of the cerebral cortex; stratum pyramidale, stratum radiatum, and stratum oriens of the hippocampus; and stratum moleculare of the dentate gyrus. Within the cerebellum, higher densities of binding were observed in the molecular layer than in the granule cell layer. In many regions, [3H]AMPA binding had a similar distribution to that of L-[3H]glutamate binding displaced by AMPA (1 microM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2881602 TI - RU38486 blocks the steroid regulation of transmitter choice in cultured rat sympathetic ganglia. AB - Sympathetic neurones grown in tissue culture change phenotype from adrenergic to cholinergic due to a factor released by non-neuronal cells. Glucocorticosteroids prevent the production of this factor by non-neuronal cells and hence prevent the change in phenotype. Conventional steroid antagonists, however, fail to block this effect. We report here that the steroid antagonist RU38486 is effective in preventing the action of corticosterone on cultured sympathetic ganglia and hence may be a useful in vivo tool to study the steroid regulation of development. PMID- 2881603 TI - Selective loss of monoaminergic neurons in weaver mutant mice--an immunocytochemical study. AB - Tyrosine hydroxylase (TH) immunocytochemistry and quantitative light microscopic analysis of neurons in the substantia nigra pars compacta, the ventral tegmental area, and the locus coeruleus of weaver mutant mice at 12 and 15 weeks of age and unaffected controls revealed a decrease in the number of TH-positive neurons in the substantia nigra of weaver mice, but no change in cell numbers in the ventral tegmental area and locus coeruleus. Furthermore, the 15-week-old mutants showed a significant cell loss in the substantia nigra pars compacta compared with the 12 week-old group. Thus, the weaver mutant may provide a good model for studying the mechanisms of selective dopaminergic cell loss. PMID- 2881604 TI - Somatostatin and calcitonin stimulate neurite regeneration of molluscan neurons in vitro. AB - Isolated neurons from the gastropod Physella heterostropha fail to regenerate their neurites if cultured in defined medium in the absence of growth factors. A significant number of cultured neurons extend neurites if they are cultured in brain-conditioned or hemocyte-conditioned medium. Synthetic somatostatin and salmon calcitonin also stimulate neurite regeneration in a dose-dependent manner. Thyrotropin-releasing hormone, arginine vasotocin, and eledoisin fail to promote neurite outgrowth. It is concluded that, like other molluscan neurons, isolated neurons from Physella require the presence of factors that are released by brain tissue or are present in the hemolymph, and that somatostatin and calcitonin can, in part, substitute for the endogenous neurite-regenerating activities. PMID- 2881605 TI - Phorbol esters enhance transmitter release in rat hippocampal slices. AB - Phorbol esters enhance synaptic transmission in the rat hippocampal slice preparation most likely by acting at a presynaptic locus. To more directly examine the actions of phorbol esters on neurotransmitter release we have measured their effects on the occurrence of spontaneous postsynaptic potentials as well as on the potassium stimulated release of endogenous glutamate. Both measures of transmitter release were increased by phorbol esters suggesting a functional or regulatory role for protein kinase C in controlling the release of neurotransmitter in the mammalian CNS. PMID- 2881606 TI - Urinary bladder intramural neurones: an electrophysiological study utilizing a tissue culture preparation. AB - An enzymic dispersion technique was used to free the intramural ganglia from their usual close association with the other components of the urinary bladder wall. The isolated ganglia obtained were viable and could be kept in culture for several weeks. The development of the cultures was monitored by phase-contrast microscopy and their electrophysiological properties were investigated using intracellular recording techniques. Neurones could be visually identified after 2 3 days in culture; cell groups contained from 2-50 neurones. Three types of spontaneous activity were seen: small changes in membrane potential and action potentials, and slow oscillatory conductance changes. These events were not blocked by hexamethonium but were abolished by hyperpolarizing current. Most neurones spiked without adaptation to direct stimulation; in a few cells the train of spikes was damped out. No neurones generated long afterhyperpolarizations. Indirect stimulation produced responses in the ganglia which are consistent with synaptic activity. Summation of inputs was demonstrated. These results provide evidence for local intraganglionic circuits since the ganglia or neurone groups are unequivocally extrinsically denervated. It was concluded that the intramural ganglia have the capacity to integrate preganglionic input and the question of whether or not they might mediate reflex activity is raised. PMID- 2881608 TI - Dextrorphan and dextromethorphan attenuate glutamate neurotoxicity. AB - The dextrorotatory morphinan opioid, dextrorphan, which has recently been reported to block the excitation of cortical neurons by N-methyl-D-aspartate, was found at 10-100 microM concentrations to attenuate both morphological and chemical evidence of glutamate neurotoxicity in murine neocortical cell cultures; a similar effect was found with its methyl ester derivative, dextromethorphan. Given other data suggesting that glutamate neurotoxicity may participate in the pathogenesis of the central neuronal loss associated with certain human neurological diseases, the present observations raise the possibility that these clinically tested opioids, or related compounds, may eventually prove to have some clinical therapeutic utility. PMID- 2881607 TI - Spinal monoamine mediation of stimulation-produced antinociception from the lateral hypothalamus. AB - Stimulation-produced antinociception can be evoked from a wide variety of sites in the brain, including the lateral hypothalamus (LH). The present study, in rats lightly anesthetized with pentobarbital, examined descending inhibition of the nociceptive tail flick (TF) reflex produced by focal electrical stimulation in the LH and the neurotransmitter(s), at the level of the lumbar enlargement, mediating the inhibition. Systematic tracking studies demonstrated that stimulation in the diencephalon dorsal to the hypothalamus did not reliably inhibit the TF reflex. Inhibition of the TF reflex was produced, however, throughout the hypothalamus at intensities of stimulation typically between 50 and 200 microA. The area requiring low intensities of stimulation (50-100 microA) to inhibit the TF reflex was a diffuse region of the LH, inferior to the mammillothalamic tract and internal capsule, medial to the supraoptic decussation and including the medial forebrain bundle. Microinjections of S-glutamate (100 mM, 0.5 microliter) in the LH did not inhibit the TF reflex, suggesting that activation of fibers of passage by stimulation was responsible for inhibition of the TF reflex produced from the LH. The intrathecal administration of pharmacologic antagonists (15-30 micrograms; naloxone, methysergide, phentolamine, prazosin or yohimbine) revealed that the alpha-adrenoceptor antagonists phentolamine and yohimbine produced the greatest increases in stimulation thresholds in the LH for inhibition of the TF reflex (83.7% and 89.8%, respectively). The intrathecal administration of methysergide produced a lesser, but statistically significant 11% increase in the stimulation threshold for inhibition of the TF reflex. These results indicate that spinal alpha 2 adrenoceptors primarily mediate the descending inhibition of the TF reflex produced by electrical stimulation in the LH. PMID- 2881610 TI - Increase in glutamate sensitivity of subthalamic nucleus neurons following bilateral decortication: a microiontophoretic study in the rat. AB - Responses of subthalamic neurons (STN) to the iontophoretic application of glutamate (Glu), acetylcholine (ACh) and GABA were studied in rats 2 or 3 weeks following bilateral decortication, and were compared to those obtained in normal animals. All the cells recorded in lesioned rats showed a decrease in their spontaneous firing rate. They also proved to be significantly more sensitive to the excitatory action of Glu, although their responsiveness to ACh or GABA was not modified. PMID- 2881609 TI - Postnatal development of neurons containing both catecholaminergic and GABAergic traits in the rat main olfactory bulb. AB - Postnatal development of catecholaminergic and gamma-aminobutyric acid (GABA) ergic neurons in the periglomerular region of the rat main olfactory bulb was studied immunohistochemically using antisera against tyrosine hydroxylase (TH), glutamic acid decarboxylase and GABA. TH-like immunoreactive neurons almost always contained GABA-like immunoreactivity in the first postnatal week, but about 10% of them did not contain GABA-like immunoreactivity in older animals. PMID- 2881611 TI - Multiple types of neurotransmitter binding sites in the rat neuroblastoma B 50 cell line. I. Characterization and binding affinity changes during various differentiation paradigms. AB - In this study, it is shown that the neuroblastoma B 50 cell line of rat central nervous system origin possesses both adrenergic and cholinergic binding sites. The adrenergic binding site population comprises a major alpha 1-adrenergic component (using [3H]prazosin as ligand; KD = 0.55 nM; 19.3 fmol/mg protein), and a minor beta-adrenergic species (KD = 0.45 nM; 3.4 fmol/mg protein using [125I]cyanopindolol as ligand). The cholinergic binding site is of a muscarinic type. Binding studies with quinuclidinyl benzylate (QNB) indicate the presence of two binding sites with different affinities. This is supported by competition studies with agonists. However, in view of this unusual binding behavior of the antagonist, the possibility of a one-site model for QNB is also considered and affords the following parameters: KD = 0.247 nM, Bmax = 29.6 fmoles/mg protein. When the cells are induced to differentiate with dibutyryl cyclic AMP (db-cAMP) or high extracellular calcium, all of these binding sites undergo a variety of changes in their affinities for their respective ligands. Db-cAMP increases the affinity of the alpha 1-site for prazosin while high extracellular calcium lowers it. In both cases the number of binding sites remains unchanged. The affinity of the beta-adrenergic component is markedly enhanced upon induction of differentiation with either extracellular calcium or/and db-cAMP. Finally, the muscarinic cholinergic binding sites exhibit a decrease in receptor number upon db-cAMP treatment and an apparent loss of one of the binding sites upon calcium treatment. The significance of these affinity changes is discussed for each type of binding site. PMID- 2881612 TI - Multiple types of neurotransmitter binding sites in the rat neuroblastoma B 50 cell line. II. Response of second messenger systems to physiological stimuli in proliferating and differentiated cells. AB - The functionality of the alpha 1-, beta-adrenergic and muscarinic cholinergic binding sites of neuroblastoma B 50 is investigated under proliferating and differentiating conditions. In proliferating cells, the stimulation of the alpha 1-adrenergic and muscarinic cholinergic binding sites by their respective agonists causes an increase in both extracellular calcium association with the cells and phosphatidylinositol (PI) turnover; effects usually associated with functional receptors. When the cells are induced to differentiate morphologically with dibutyryl cyclic AMP (db-cAMP), extracellular calcium or a combination of both, the activity of the muscarinic receptor-coupled PI turnover is strictly correlated with the binding affinity of the receptor. This is not the case for the alpha 1-adrenergic receptor stimulation of PI turnover. The latter result, however, may be explained in terms of the intrinsic properties of the inducing agents used to cause neurite extension. The stimulation of the beta-adrenergic binding site with isoproterenol in proliferating cells, both with and without a phosphodiesterase inhibitor present, does not result in cellular cAMP accumulation. In morphologically differentiated cells, only the db-cAMP-induced state exhibits an increase in [3H]adenosine incorporation into cellular cAMP upon isoproterenol stimulation. This happens only in the presence of a phosphodiesterase inhibitor. The data presented in this study are discussed in terms of the affinity of the receptors for their respective ligands and in terms of the intrinsic properties of the inducing agents. PMID- 2881614 TI - Genetic determination of hypothalamic tyrosine hydroxylase activity in mice. AB - Tyrosine hydroxylase (TH) activity data obtained from hypothalamic tissue samples of highly inbred mouse strains with known differences in their mesencephalic TH activity (BALB/cJ, C57BL/6ByJ, CXBI/ByJ), F1 hybrids and F2 generations were subjected to quantitative genetic analysis. No differences were observed between C57BL/6ByJ and CXBI/ByJ strains, but highly significant differences were found in hypothalamic TH activity between BALB/cJ and C57BL/6ByJ strains. Segregating genetic factors could not be detected in the replicate (C57BL/6ByJ X CXBI/ByJ) F2 generations, while the presence of segregating genetic units was indicated in the (C57BL/6ByJ X BALB/cJ)F2 population. Estimation of minimum number of genes and Elston's non-parametric one-locus test reveal that more genes are responsible for strain differences of TH activity in the hypothalamus compared to the dopaminergic areas of the mesotelencephalon. The results indicate that the heterogeneity of the catecholamine neuronal populations and terminal fields in the hypothalamus is reflected by the complex nature of the genetic control of TH activity in this brain region. PMID- 2881613 TI - Gliogenesis in the embryonic avian optic tectum: neuronal-glial interactions influence astroglial phenotype maturation. AB - We have analyzed the development of neuroglial cells in the chick optic tectum under 3 sets of developmental conditions to assess the role of heterotypic cell cell interactions in gliogenesis. Immunochemical and biochemical methods were employed to measure and localize the expression of the glial markers glutamine synthetase, glial fibrillary acidic protein, S-100 protein, carbonic anhydrase-C and myelin basic protein as functions of development in situ and in aggregation and monolayer cultures of dissociated embryonic tissue. The results showed that certain astroglial cells can be recognized as early as day 9 of development in situ. Oligodendroglial development manifests several days later and the full range of glial subtypes are not evident until nearly the time of hatching. Culture of 7-day embryonic tectum cells either in aggregates or in monolayer cultures failed to yield definitive oligodendroglia. Fibrous astroglia, as defined by glutamine synthetase and glial fibrillary acidic protein, developed well in both culturing systems. However, as previously noted in the embryonic neural retina system, glutamine synthetase expression was marked dependent on neuronal-glial associations. PMID- 2881615 TI - Quantitative autoradiographic analysis of somatostatin binding sites in discrete areas of rat forebrain. AB - Somatostatin has been localized in several hypothalamic and extrahypothalamic brain regions where it may function as a classical neurotransmitter or as a modulator of neural activity. In the present study, somatostatin binding sites were studied by incubation of coronal sections of rat forebrain with 125I-Tyr1 somatostatin, Ultrofilm autoradiography, computerized microdensitometry and comparison with 125I standards. Highest concentrations of somatostatin binding sites (fmol/mg protein) were found in the claustrum (151), basolateral nucleus of the amygdala (90), deep layers of the cerebral cortex (61), lateral olfactory nuclei (58), CA1 and CA2 areas of hippocampus (57), medial and lateral septal nuclei (54), and the medial habenula (44). Scatchard analysis of individual forebrain areas with high densities of somatostatin binding sites was also performed. Regulation of brain somatostatin binding sites may be studied as one approach to examining the involvement of central somatostatin pathways in various physiological and behavioral states. PMID- 2881616 TI - [Effect of forskolin and VIP on the release of somatostatin and the cAMP content of cultured rat diencephalon neurons]. AB - Forskolin, a direct activator of adenylate cyclase, stimulates somatostatin release in dispersed fetal diencephalic cells in culture (10 j). It was found that concentrations ranging from 10(-8) M to 10(-4) M increase the release of somatostatin in a dose-dependent manner, as well as the formation of intracellular cyclic AMP. Furthermore, VIP (10(-6) M) which produces a significant (p less than 0.03) elevation of SRIF release at 30 min of incubation, also induces a prompt increase of intracellular cyclic AMP (10 min). These results suggest that VIP could stimulate the somatostatin release through a cyclic AMP-dependent mechanism. PMID- 2881617 TI - [Oral premedication with bromazepam and lorazepam]. PMID- 2881618 TI - Cytogenetic studies on patients with medullary carcinoma of the thyroid. AB - Cytogenetic studies were carried out on stimulated lymphocyte cultures of patients with medullary carcinoma of the thyroid. Of 32 patients studied, seven had a hereditary carcinoma, and five had multiple endocrine neoplasia type 2A and two had type 2B. Neither a constitutional chromosome abnormality nor an increase in chromosomal breakage were detected in these patients. PMID- 2881619 TI - Clarification of the chromosomal assignment of the human P-glycoprotein/mdr1 gene: possible coincidence with the cystic fibrosis and c-met oncogene. PMID- 2881620 TI - Verapamil reversal of vincristine resistance and cross-resistance patterns of vincristine-resistant Chinese hamster ovary cells. AB - The phenotypic properties of a large number of low-level vincristine (VCR) resistant Chinese hamster ovary cell lines have been studied. In particular, we examined the correlation between the reversal of VCR resistance by verapamil (VRP) and cross-resistance patterns to other drugs. Cross resistance to other vinca alkaloids developed in parallel with VCR resistance. Doxorubicin resistance was observed in many of the cell lines, occurring even at the lowest levels of VCR resistance. Increased sensitivity to taxol (TAX) was a feature of half of the lines tested and there was no increased resistance to 5-fluorouracil or chlorambucil. Two main groups of mutants have been identified: (a) those that are thought to be membrane mutants which are cross-resistant to TAX and whose VCR resistance is reversible by VRP; and (b) those that appear to be tubulin mutants, which have increased sensitivity to TAX and resistance to VCR in the presence of VRP. It was not possible to distinguish between the different mechanisms of low level resistance by drug accumulation studies in unsupplemented medium. However, VCR accumulation in the presence of VRP did correlate with the cross-resistance results. PMID- 2881621 TI - Effects produced by SCN- and thioglycolate on isolated nematocysts of Pelagia noctiluca. PMID- 2881623 TI - Excitation of neurons in the canine area postrema by prostaglandins. AB - The effects of prostaglandins on electrical activity of neurons in the canine area postrema were studied using the techniques of extracellular recording with iontophoresis. Excitatory responses were obtained upon application of prostaglandins A1, B1, B2, E1, F1 alpha, and F2 alpha in between 24 and 50% of the cells studied. The excitation was very similar in pattern to that observed to apomorphine, biogenic amines, and several neuropeptides in that it had a relatively long latency, low maimal frequency, and prolonged duration. Since the area postrema is known to play a central receptive role in initiating emesis to circulating toxins, these results suggest that prostaglandins may play a role in the initiation of some forms of emesis. PMID- 2881622 TI - Electrophysiological actions of somatostatin (SRIF) in hippocampus: an in vitro study. AB - The electrophysiological actions of somatostatin (somatotropin release inhibiting factor; SRIF) were investigated in the in vitro hippocampal slice preparation. Intracellular recordings were obtained from pyramidal neurons in area CA1 in slices of hippocampus from guinea pigs and rabbits. Somatostatin, applied via micropressure ejection to CA1 pyramidal-cell somata, was primarily excitatory. The effects, however, were quite variable, with nearly all cells displaying pronounced tachyphylaxis. A majority of cells was depolarized by SRIF, but hyperpolarizations or biphasic depolarization/hyperpolarization responses were also recorded. Only minimal conductance changes were associated with the SRIF induced voltage changes. Depletion of SRIF, by injection of the intact animal with cysteamine several hours before preparing slices, resulted in no obvious abnormalities in hippocampal slice electrophysiology. Our results obtained with application of exogenous SRIF are consistent with the concept that SRIF acts as an excitatory neurotransmitter/neuromodulator in hippocampus. However, our attempts to demonstrate endogenous SRIF action have thus far been unsuccessful. PMID- 2881624 TI - Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene. AB - Two glucocorticoid response elements (GREs) located 2.5 kb upstream of the transcription initiation site of the tyrosine aminotransferase gene were identified by gene transfer experiments and shown to bind to purified glucocorticoid receptor. Although the proximal GRE has no inherent capacity by itself to stimulate transcription, when present in conjunction with the distal GRE, this element synergistically enhances glucocorticoid induction of gene expression. Cooperativity of the two GREs is maintained when they are transposed upstream of a heterologous promoter. An oligonucleotide of 22 bp representing the distal GRE is sufficient to confer glucocorticoid inducibility. As evidenced by the mapping of DNAase I hypersensitive sites, local alterations in the structure of chromatin at the GREs take place as a consequence of hormonal treatment. PMID- 2881626 TI - [Takayasu's arteritis. Course of ophthalmological signs after vascular graft. Apropos of a case]. PMID- 2881625 TI - A comparison of the beta-adrenoceptor agonist potency of labetalol with those of sympathomimetic drugs, and the role of alpha-receptors in pharmacological actions of these drugs on tracheal smooth muscles in guinea pigs. PMID- 2881627 TI - Inconsistent effects of all-trans retinoic acid on different clones of chemically transformed rat liver epithelial cells. AB - The effects of all-trans retinoic acid (RA) on the growth and biochemical properties of five clonal strains of neoplastically transformed rat liver epithelial cells were studied. These cell strains were derived clonally from a single line of normal diploid rat liver epithelial cells that had been transformed by treatment with N-methyl-N'-nitro-N-nitrosoguanidine. The results show that RA induces inconsistent alterations in selected phenotypic properties of these five different cell strains. Retinoic acid either depressed, enhanced or produced no effect on the colony-forming ability in soft agar, on the activity of gamma-glutamyl transpeptidase, on the amount of cell-associated fibronectin, and on the binding capacity of 125I-epidermal growth factor (EGF). The only consistent correlation observed among cell strains was between the cellular ability to grow in soft agar and the amount of cell-associated fibronectin. Enhancement of anchorage-independent growth by retinoic acid was not mediated through changes in the number of EGF receptors. Our data demonstrate that the responses to retinoic acid of clonal subpopulations of chemically transformed rat liver epithelial cells are inconsistent, even when the clonal subpopulations are derived from a common precursor. PMID- 2881628 TI - Persistent effect of a low dose of preadministered diethylnitrosamine on the induction of enzyme-altered foci in rat liver. AB - The effect of a low dose of preadministered diethylnitrosamine (DEN) on the induction of enzyme-altered foci in the livers of male full-grown Fischer 344 rats was studied. As a pretreatment, DEN at a dose of 10 mg/kg body wt was injected i.p. At various times after DEN pretreatment a complete initiation, consisting of administration of the same dose of DEN by the same route in rats subjected to partial hepatectomy (PH), was performed, followed by application of selection pressure. Enzyme-altered foci stained with gamma-glutamyltranspeptidase (gamma-GTP) and glutathione S-transferase placental form (GST-P) were then assayed. Decreases in the numbers and areas of foci in the rats which received saline + PH 14 or 28 days after DEN pretreatment were observed in comparison with rats which received saline + PH immediately after DEN. On the other hand, the numbers and areas of foci were not decreased in rats which received the complete initiation, consisting of DEN + PH, at various times after DEN pretreatment when compared with rats which received these at the same time as the DEN pretreatment. This persistent effect of DEN pretreatment on the complete initiation lasted up to 182 days after the time of DEN pretreatment. In this experiment, GST-P was found to be a more sensitive marker for the detection of putative preneoplastic liver-cell foci than gamma-GTP. PMID- 2881629 TI - Inhibition by pentachlorophenol of the initiating and promoting activities of 1' hydroxysafrole for the formation of enzyme-altered foci and tumors in rat liver. AB - The hepatocarcinogen 1'-hydroxysafrole (HOS) exhibited weak initiating activity and strong promoting activity for the induction of enzyme-altered foci and tumors in rat liver. Thus, administration of a single dose of HOS to rats 18 h after a 70% hepatectomy, followed by administration of phenobarbital (PB) in the diet for 6 months, induced a low, but statistically significant, number of foci of enzyme altered cells. This treatment did not result in gross liver tumors, even when the PB treatment was continued for 16 months. Large numbers of enzyme-altered foci developed when HOS was administered in the diet at levels of 0.05-0.25% to rats previously administered a single dose of N,N-diethylnitrosamine (DEN) 24 h after a 70% hepatectomy. Similarly, rats given a single dose of DEN 24 h after a partial hepatectomy and then fed 0.10 or 0.25% of HOS in the diet for 10 months developed a high incidence of hepatocellular carcinomas. In the absence of pretreatment with DEN, dietary administration for at least 4 months of 0.10 or 0.25% of HOS induced significant numbers of enzyme-altered foci; these data and liver tumor induction by continuous feeding of HOS, in the absence of pretreatment with DEN, provide additional evidence for an initiating, as well as a promoting, activity of HOS in rat liver. Concurrent administration of the hepatic sulfotransferase inhibitor pentachlorophenol with HOS in each of the above assays almost completely inhibited the initiating and promoting activities of HOS for the formation of enzyme-altered foci and tumors; these data strongly suggest that both the initiating and promoting activities are mediated by the sulfuric acid ester, 1'-sulfooxysafrole. HOS also exhibited initiating activity in adult mouse liver. Thus, dietary administration of 0.25% of HOS for only 1 month, followed by administration of the hepatic tumor promoter 1,4-bis[2-(3,5 dichloropyridyloxy)]benzene resulted in a high incidence and multiplicity of hepatomas by 10 months. In the absence of the promoter, administration of HOS for only 1 month induced no hepatomas; 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene alone induced only a low incidence. In mice not given the promoter, continuous administration of HOS for 3-6 months was required for hepatoma development by 16 months. PMID- 2881630 TI - Effect of a long-acting analogue of somatostatin, SMS 201-995, on the development of intestinal tumours in azoxymethane-treated rats. AB - The effect of daily parenteral administration of a long-acting analogue of somatostatin (SMS 201-995) on the development of intestinal tumours and the rate of crypt cell proliferation in azoxymethane-treated rats has been studied. SMS 201-995 had no significant effect on the number of colonic tumours induced. In the duodenum, SMS 201-995 administration was associated with a change in the number of tumours from 1.4/rat in saline-treated animals to 2.4/rat in animals treated for the last third of the study and 2.8/rat in animals treated with SMS for the entire duration of the study (P less than 0.02). SMS had no significant effect on the rate of cell proliferation in the duodenum, ileum or colon. The inhibition of release of gastrointestinal trophic hormones by this analogue of somatostatin thus does not appear to reduce the number of tumours in the intestine of azoxymethane-treated rats. PMID- 2881631 TI - The clonal nature of carcinogen-induced altered foci of gamma-glutamyl transpeptidase expression in rat liver. AB - The clonality of tumors has been convincingly established. Because it is generally accepted that tumor formation involves a number of steps, it is important to determine which if any of the precursors of tumors are clonal. A series of chimeric rats produced between congenic strains by morulae aggregation were used to establish the cellular composition of foci of gamma-glutamyl transpeptidase (gamma-GTP; E.C. 2.3.2.2) expression in liver following initiation with N-nitrosodiethylamine and promotion with phenobarbital. The chimeras were produced between congenic rat strains (PVG and PVG-RT1a) genetically distinguished by alleles of the major histocompatibility complex (MHC). Monoclonal antibodies directed to distinctive class I MHC alloantigens were used to detect patterns of mosaicism in the animals. The parental genotypes present in most visceral tissues could be easily distinguished by our method. Analysis of 499 enzyme-altered foci revealed that 474 were comprised solely of either PVG RT1a or PVG cells. Some apparent mixture of cells from the two lineages was observed in 25 lesions, most of which were very small. The observed pattern of distortion of normal patch distribution clearly indicated the expanding and clonal nature of these lesions. PMID- 2881632 TI - Autoradiographic studies on in vivo covalent binding of N-hydroxy-2 acetylaminofluorene in rat liver containing gamma-glutamyltranspeptidase-positive foci. The effect of the sulfation-inhibitor pentachlorophenol. AB - The role of sulfation in the covalent binding of [ring-3H]-N-hydroxy-2 acetylaminofluorene (N-OH-AAF) in rat liver containing gamma glutamyltranspeptidase-positive (GGT+) foci was studied in vivo by autoradiography. GGT+ foci were induced by initiation with diethylnitrosamine, followed by a selection protocol consisting of a 2-week exposure to 2 aminofluorene in the drinking water and a single administration of CCl4. Both surrounding ('normal') liver tissue and, to a lesser extent, GGT+ foci covalently bound N-OH-AAF, administered 10 days after selection. The sulfation inhibitor, pentachlorophenol (PCP), reduced the covalent binding of N-OH-AAF in cells surrounding the foci. However, PCP had no effect on binding of radiolabel in GGT+ foci. Thus, reduced sulfotransferase activity may contribute to the resistance of GGT+ preneoplastic lesions to carcinogen cytotoxicity. The results suggest also, that cells in GGT+ foci are able to bind N-OH-AAF covalently by a sulfotransferase-independent pathway. PMID- 2881633 TI - Effects of separate and combined treatments with gamma radiation and diethylnitrosamine in neonatal rats on the induction of altered hepatocyte foci and hepatic tumors. AB - To characterize the effects of combined treatments with gamma radiation and diethylnitrosamine (DEN) on the induction of histochemically detectable altered hepatocyte foci and hepatic tumors, we assessed the yields of these lesions in the livers of 150-day-old rats that had been treated neonatally with a single dose of gamma radiation (75 rad, whole body) and i.p.-injected DEN (0.15 mumol/g body wt), either separately or in combination. The combined treatments involved the administration of the two stimuli in both possible sequences, with the interval between treatments set at 1 h. The focus population was examined for two histochemical markers (elevated gamma-glutamyl transpeptidase [GGT(+)] and iron exclusion [FE(-)], giving rise to three detectable focus phenotypes, i.e. GGT(+) foci, FE(-) foci, and GGT(+), FE(-) foci. Frequencies of the three phenotypes were quantitated through the use of serial frozen sectioning techniques and computer-assisted image analysis. GGT(+) focus induction was synergistically enhanced by the combined treatment irrespective of the order in which the two stimuli were administered; the remaining two phenotypes did not show such enhancement. The magnitude of the GGT(+) focus response was significantly greater when the treatment sequence was gamma----DEN as opposed to DEN----gamma. Tumor yields in rats receiving combined gamma--DEN treatment were similar to those in rats receiving the DEN alone, irrespective of the gamma--DEN treatment sequence. These results suggest that phenotypically distinguishable lesions, including foci with different histochemical marker patterns and tumors, originate from specific types of damage at different genetic loci and are developmentally independent; and the expression of the GGT(+) marker per se in altered hepatocyte foci is not a reliable index of incipient hepatic neoplasia. PMID- 2881635 TI - Long-term nitroglycerin treatment: effect on direct and endothelium-mediated large coronary artery dilation in conscious dogs. AB - We examined the effect of nitroglycerin (GTN) tolerance on an important determinant of nitrate-antianginal action, large coronary artery dilation, in 11 chronically instrumented conscious dogs. In addition, endothelium-mediated coronary artery dilation was studied because this shares a common dilator pathway with the nitrates, i.e., activation of soluble guanylate cyclase. With long-term GTN (1.5 micrograms/kg/min iv for 5 days) the diameters of the left circumflex and anterior descending coronary arteries showed an initial increase of 8.2 +/- 0.3% and 10.8 +/- 0.9%, respectively, returning to control levels by the second to third day of treatment. On days 4 and 5, the dose-response relations for GTN induced epicardial artery dilation were shifted (p less than .01) to 17- to 20 fold higher doses. However, there was no attenuation of epicardial artery dilation induced by SIN-1 (n = 7), another activator of guanylate cyclase, or of endothelium-mediated dilation assessed both as flow-dependent dilation (n = 7) and as direct intra-arterial acetylcholine-induced dilation (n = 4). In addition, there was no clear tolerance to the peripheral vascular actions of GTN responsible for reflex tachycardia and increased coronary flow. We conclude that a moderate degree of nitrate tolerance to epicardial artery dilation does not affect the responsiveness to other exogenous or endogenous activators of guanylate cyclase. However, this tolerance to epicardial artery dilation, together with the maintenance of peripheral vascular actions that can induce reflex tachycardia, result in a potentially unfavorable balance of GTN effects. PMID- 2881634 TI - Increased sensitivity of the denervated transplanted human heart to isoprenaline both before and after beta-adrenergic blockade. AB - It is not known whether surgical denervation leads to increased beta-receptor sensitivity after human cardiac transplantation. We assessed cardiac beta receptor sensitivity by studying the heart rate response to isoprenaline of the denervated donor heart as compared with the innervated recipient heart in eight patients who underwent heterotopic cardiac transplantation and in six patients with orthotopic transplantation. Changes in the donor and recipient hearts seen in these 14 patients were further compared with those seen in 10 normal volunteers. Incremental intravenous infusion of isoprenaline (5, 10, and 15 ng/kg/min) raised heart rate to a greater extent in the donor compared with the recipient hearts in the eight patients who had heterotopic grafts (slopes [beats/min/ng/kg]: donor = +2.26, recipient = +1.59; p less than .01). In addition, the donor hearts of the transplant patients were more sensitive than hearts of the normal volunteers (slopes: donor = +2.26, normal = +0.94; p less than .01). The changes in the two groups of donor hearts were similar (slopes: orthotopic = +2.24, heterotopic = +2.27; NS). The recipient hearts in the patients with heterotopic transplants were more sensitive than the hearts of the normal volunteers (p less than .05), suggesting that the observed differences in isoprenaline sensitivity in the patients with heterotopic grafts were not caused by a decreased sensitivity of the recipient heart. After beta-blockade, the heart rate responses to isoprenaline were attenuated to the same extent in denervated and innervated hearts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881637 TI - Genetic heterogeneity in X-linked agammaglobulinemia complicates carrier detection and prenatal diagnosis. AB - X-linked agammaglobulinemia (XLA) is a severe antibody deficiency disease reflecting an arrest of B lymphocyte differentiation at the level of precursor B cells. The disease is inherited in an X-linked recessive mode. In a single eight generation pedigree the XLA gene was mapped to the Xq21.3-Xq22 area of the X chromosome. The data establish close linkage of the XLA locus to the DXS17 restriction fragment length polymorphic (RFLP) marker locus (the lod score exceeding 6 at phi = 0). A series of RFLP markers around the DXS17 locus provided an RFLP haplotype of use in genetic counselling within this pedigree. In one other pedigree a phenotypically identical disease was inherited but was accompanied by a high frequency of recombination with the DXS17 locus, which made localisation of the gene at the DXS17 locus highly unlikely (lod score less than 3). This genetic heterogeneity complicates genetic counselling within particular pedigrees, especially when the localization of the XLA gene involved in those pedigrees has not been established. PMID- 2881636 TI - Pseudodeficiency of arylsulfatase A: a counseling dilemma. AB - Arylsulfatase A (ASA) deficiency is the cause of early and late onset metachromatic leukodystrophy (MLD). Low ASA levels are detected in some healthy individuals who are pseudodeficient (PD). PD individuals can be distinguished, because PD fibroblasts hydrolyze 14C-sulfatide at similar rates to normal fibroblasts. This has also been demonstrated in amniocytes and chorionic villi (CV). The genetic basis for PD is not clearly understood and is most likely heterogeneous with respect to allelic mutations of the ASA gene. It is hypothesized that the PD phenotype can either be due to PD/PD or PD/MLD genotypes, only the latter representing a potential risk to offspring. We report an unusual family where two siblings, both carriers of the classic late infantile MLD allele, are married to unrelated PD individuals. One couple has two PD offspring; their "at risk" status, due to the lack of an affected offspring is in question. The other couple terminated a fetus determined to be affected with a "MLD variant", most likely a compound heterozygote. Cautions prenatal counseling of PD families is essential. The population frequency of the PD phenotype is unknown. PMID- 2881638 TI - HTLV-I antibody and cell-mediated immunity status in sickle cell anemia. AB - Patients with sickle cell anemia (SCA) had an abnormal susceptibility to infections. In Martinique (French West Indies), a human T-cell leukemia/lymphoma virus type I (HTLV-I) endemic area, we found that 17 (10%) of 173 SCA patients had antibodies to HTLV-I. The possible relationship between HTLV-I seropositivity and altered immunity was studied in 13 SCA patients with HTLV-I antibodies compared with 13 matched SCA patients without HTLV-I antibodies. The immunological results, as evaluated by the T-cell subsets analysis, the lymphocyte proliferation responses analyzed after activation with concanavalin A, phytohemagglutinin, or pokeweed mitogen, and the natural killer activity were not statistically different in these two groups of patients (SCA HTLV-I positive vs SCA HTLV-I negative). These data suggest that HTLV-I infection did not result in a major alteration of cellular immunity in this population. PMID- 2881639 TI - [Neurotransmitter abnormalities in the dementia of Alzheimer type]. PMID- 2881640 TI - Further studies of plasma protease inhibitors in the hedgehog, Erinaceus europaeus; collagenase, papain and plasmin inhibitors. AB - Hedgehog plasma was separated by gel filtration on Sephacryl S-200, the fractions resolved by electrophoresis and the electrophoretograms characterized for collagenase, papain and plasmin inhibiting activities with the high mol. wt substrate casein. The three inhibitors previously identified as alpha 2-, alpha 2 beta- and beta-macroglobulins were found to inhibit all three proteases. These were the only collagenase inhibitors found in plasma. Hedgehog alpha 2 chymotrypsin inhibitor and beta-protease inhibitor were both found to also inhibit papain. Three new inhibitors specific for papain (gamma-, alpha 2- and alpha 1-cysteine protease inhibitors) and one for plasmin (alpha 2-antiplasmin) were also found, bringing the number of protease inhibitors in hedgehog plasma to 14. Immunological cross-reactivity as studied by immunoelectrophoresis showed homology between hedgehog alpha 2-macroglobulin and rat murinoglobulin I and between hedgehog alpha 2-antithrombin and rat antithrombin III. PMID- 2881641 TI - Cysteamine-induced duodenal ulcer: effects on calcium absorption across rat duodenum. AB - The effect of cysteamine-induced duodenal ulcers on calcium transport across rat duodenum was investigated. Intracellular calcium accumulation measured after 24 hr and 3 days of cysteamine injection showed a significant increase (P less than 0.001) in the duodenal strips isolated after 3 days with no change noticed in those isolated after 24 hr, although the morphological changes in both were very similar. The relationship between increasing calcium concentration in the incubation medium and intracellular calcium concentration is a saturable process that conforms to the Michaelis-Menten type of kinetics. The average maximal flux (Vmax) increased from 8.93 nmole/hr-gdw in normal to 12.5 nmole/hr-gdw in 3-day ulcerated rats, with no apparent change in the Michaelis constant (Kt) (0.8 mM). Unidirectional influx of calcium across the mucosal membrane was significantly increased (P less than 0.001) in 3-day-ulcerated duodenum suggesting that the increase in calcium transport could be due to the activation of the active step at the mucosal border. PMID- 2881642 TI - Respiratory function of a unit of blood volume in the Little Auk (Plautus alle) and the arctic tern (Sterna paradisaea). AB - The indices of red blood were determined in nestlings and adults of Plautus alle and adults of Sterna paradisaea. All measured parameters varied significantly, but the amount of Hb per unit area of erythrocytes did not change over the nestling development of P. alle. In adult P. alle, S. paradisaea and 12 compared species of birds from the temperate zone, the amount of Hb per unit area of erythrocytes was very close. The mechanism determining the level of the respiratory function of a unit blood volume in birds is similar, but differs from that in mammals. PMID- 2881643 TI - The effect of the internal Na concentration on the electrogenicity of the insulin stimulated Na,K-pump in frog skeletal muscles. AB - Insulin induced a hyperpolarization of the membrane by stimulating the Na,K-pump in frog skeletal muscles. The Na,K-pump activity was dependent on the internal Na concentration. As the internal Na concentration was raised from 5 mmol/kg muscle water to 18 mmol/kg muscle water, the magnitude of the insulin-induced increase in the ouabain-sensitive Na efflux (an index of the Na,K-pump activity) rose by 5 fold and the magnitude of the insulin-induced hyperpolarization rose by 8.5-fold. On the other hand, the specific membrane resistance was not significantly changed by a rise in the internal Na concentration. The Na/K coupling of the Na,K-pump was calculated at low, normal or high internal Na concentration by using the values of the insulin-induced changes in the ouabain-sensitive Na efflux and the membrane potential. As a result of the calculation, it was suggested that in frog skeletal muscles the Na/K coupling would increase with a rise of the internal Na concentration. PMID- 2881644 TI - Influence of triiodothyronine and growth hormone on growth of dwarf and normal chickens: interactions of hormones and genotype. AB - The effects of dietary triiodothyronine (T3), injections of a preparation of growth hormone (GH) (purified from chicken pituitary tissue) and their combination on growth were investigated in three lines of chickens. The three lines were the Cornell K strain (K) (a single Comb White Leghorn strain), the Cornell K strain hemizygous for the sex-linked dwarfing gene (SLD), and the Cornell K strain homozygous recessive for the autosomal dwarfing gene (ADW). A dietary T3 treatment by genotype interaction was observed. Dietary T3 (0.1 ppm) decreased growth in the K line, tended to decrease growth in the ADW line while it tended to increase growth in the SLD line. Chicken growth hormone (100 micrograms/kg body wt) alone did not affect growth in any of the lines studied. There was, however, a GH treatment by T3 treatment interaction. Chicken GH overcame the growth-depressing effects of T3 in the K and ADW lines while it tended to promote growth in T3 treated SLD birds. Dwarf (SLD) chickens had higher basal circulating GH concentrations, lower circulating immunoreactive somatomedin C concentrations, and lower circulating T3 concentrations than the K or ADW chickens. PMID- 2881645 TI - The effect of hypophysectomy on chloride balance in young-of-the-year bowfin, Amia calva. AB - The effect of hypophysectomy on chloride balance was examined in young-of-the year bowfin, Amia calva. Hypophysectomy resulted in decreased serum and total body chloride levels but not in serum and total body sodium levels. Hypophysectomy resulted in decreased chloride influx with no effect on chloride efflux or sodium fluxes. Prolactin therapy reversed the effect of hypophysectomy on electrolyte balance but caused a significant reduction in serum protein. PMID- 2881646 TI - Comparative effects of angiotensin II on osmotic water permeability in the toad (Bufo arenarum). AB - The possible relationship between the renin-angiotensin system and water balance in the toad Bufo arenarum has been indirectly explored. A positive correlation was found between the hydrosmotic response of ventral pelvic toad skin to angiotensin II (A II) and some age indicators (body weight, snout-urostyle length or head width). A different hydrosmotic response for oxytocin and isoproterenol (but not for A II) was found between four cutaneous regions of toad body. We conclude that A II may not be directly involved in the regulation of water balance mediated by water absorption across the skin of Bufo arenarum toads. PMID- 2881647 TI - Rat corticotropin, insulin and thyroid hormone levels during the acute phase response to inflammation. AB - Circulating levels of corticotropin, thyroid hormones and insulin were measured in rats at various times after turpentine-induced inflammation. Corticotropin increased rapidly showing a biphasic response with a four-fold increase at about 6-8 hr after inflammation and a 10-fold increase at 10 hr after inflammation. The response of insulin to inflammation was slower than corticotropin and the magnitude of the increase was smaller. Insulin increased by three-fold at 20 hr after inflammation. Thyroid hormone levels were depressed by turpentine inflammation. Levels fell after 4 hr and remained at low levels throughout. Administration of a cytokine preparation to rats also caused depressed thyroxine levels at short intervals after administration. However, levels increased at longer intervals after administration. This suggests that, like corticotropin and insulin, thyroid hormone levels could be under the control of immunotransmitters during the acute phase response. PMID- 2881648 TI - Occurrence of magnetic material in teleosts. AB - Fishes representing the main groups of teleosts have been investigated for magnetic material by susceptibility measurements. All the investigated species contain magnetic material. Bone samples from the skull and the vertebral column contain magnetic particles which yield a saturation magnetization in the range 10(-4) emu g-1 to 10(-3) emu g-1 in a sample. The localization of the magnetization is diffuse within the tissues connected to the bone. There are no significant differences between the amounts of magnetic material that are found in migrating or more stationary species. PMID- 2881649 TI - Accumulation of amino acids and glucose in isolated epitheliocytes from the small intestine of chickens depending on both breed and sex. AB - In an experiment with chickens breed differences were established in accumulation of 14C-lysine, methionine and glycine, as well as intra-line differences in glycine accumulation in intestinal epitheliocytes from Plymouth Rock chickens. Differences were found in both methionine and glycine accumulation, between B line and four-line hybrids as well. Methionine accumulation in epitheliocytes from the small intestine of male chickens was higher than in female chickens from A line, higher than accumulation of tryptophane in both A and C lines and accumulation of glucose in D line. In male chickens of four-line hybrid, glycine accumulation was higher than in females. PMID- 2881650 TI - Induction of rat muscle carbonic anhydrase by denervation demonstrated with immunofluorescence. AB - Immunofluorescence microscopy of carbonic anhydrase III (CA III) was performed on sections of rat anterior tibialis (AT), extensor digitorum longus (EDL) and soleus after denervation. In contralateral control muscles, CAIII was located only in type I fibres whereas following the operation, CAIII was markedly induced in type II fibers of all the muscles, most strikingly in EDL. PMID- 2881651 TI - A histochemical characterization of muscle fiber types in the avian M. stapedius. AB - The muscle fiber types and sizes in the M. stapedius (middle ear muscle) of the domestic chicken, Gallus gallus were determined histochemically on the basis of their reactions to myofibrillar adenosine triphosphatase (mATPase), succinic dehydrogenase and NADH diaphorase. Only type II fibers were identified at pH 9.4 and 4.2. At pH 4.6 three levels of activity were seen: high, intermediate and low. With the staining techniques three subtypes of fibers for oxidative enzymes, Types II1 (highly glycolytic), II12 (intermediately glycolytic and lipolytic) and II123 (highly lipolytic) were identified. Fiber diameter was also measured for the different fiber types. The average fiber diameter was around 20 micron for each fiber type. Although similar in size, the fiber types were markedly different in their histochemical properties. These findings plus those of earlier physiological studies suggest that the M. stapedius of G. gallus is a fast twitch, muscle with fibers of similar diameter showing mainly fatigue resistance characteristics. PMID- 2881652 TI - The effect of thyroxine on the oxygen consumption of the ocellated skink, Chalcides ocellatus (Forskal). AB - Acutely administered thyroxine caused significant increase in the whole body rate of oxygen consumption of C. ocellatus at temperatures between 4 and 25 degrees C. No significant increase in the oxygen consumption was observed over the voluntary body temperature range of 30-40 degrees C. PMID- 2881653 TI - Some biological activities of recombinant DNA-derived growth hormone on plasma metabolite concentrations in domestic fowl. AB - The biological activity of recombinant-DNA-derived chicken growth hormone (rcGH) has been examined in young broiler cockerels, by determining its effects on plasma concentrations of glucose, free fatty acids and alpha-amino nitrogen. A single injection of rcGH increased plasma glucose, which remained high for several hours, whereas daily treatment with rcGH for 1 week had no effect on basal plasma glucose concentrations but blunted the glucose response to a further rcGH challenge. Plasma free fatty acids were also promptly increased following acute rcGH treatment, and chronic exposure to rcGH again attenuated this response. The effects of rcGH on plasma alpha-amino nitrogen were more variable. The stress of repeated blood sampling tended to reduce alpha-amino nitrogen, and after rcGH, an increase relative to vehicle-injected controls was seen in both acute and chronically-treated birds. These data suggest that rcGH has both hyperglycaemic and lipolytic activity in chickens, and may also increase amino acid availability. PMID- 2881654 TI - Carp maturational-ovulatory gonadotropin but not carp vitellogenic gonadotropin or salmon maturational-ovulatory gonadotropin stimulates testosterone production by rat Leydig cells in vitro. AB - Carp (Cyprinus carpio) maturational-ovulatory gonadotropin, prepared from the fraction of pituitary extract adsorbed on Con A-Sepharose (Con A II) and subsequently adsorbed on CM-cellulose (Whatman CM-52), stimulated testosterone production by isolated rat Leydig cells. The fraction of carp pituitary extract unadsorbed on the immobilized lectin (Con A I) with a mol. wt of 30,000, which had previously been shown to contain vitellogenic gonadotropin, was devoid of steroidogenic activity. Salmon (Oncorhynchus keta) pituitary Con A I and Con A II fractions containing vitellogenic and maturational-ovulatory gonadotropin respectively did not enhance steroidogenesis in the same assay system. The results indicated that carp maturational-ovulatory gonadotropin resembled mammalian luteinizing hormone (LH) in its chromatographic behavior on Con A Sepharose and CM-cellulose and also in its steroidogenic activity in rat Leydig cells. However, not all teleost maturational-ovulatory gonadotropins are LH-like: the salmon hormone is a notable exception. The data further supports the distinctiveness of carp vitellogenic gonadotropin and maturational-ovulatory gonadotropin. PMID- 2881655 TI - Metabolic effects in rats drinking increasing concentrations of sea-water. AB - Research on laboratory rats confirmed that drinking sea-water when dehydrated, was not beneficial and caused impaired renal function. When the concentration of sea-water in the drinking water is gradually increased there is a gradual increase in water uptake and corresponding urine excretion. At 50% sea-water the maximum uptake and excretion is reached. Following this there is a decline in appetite, water uptake and urine secretion. When on 100% sea-water, the creatinine clearances were greater than on tap water, while urine/plasma osmolalities (U/P) averaged 7. The only higher U/P was found in animals drinking sea-water when dehydrated, i.e. a U/P of 11. The urea metabolism appears to be suited to either the need to conserve body water, up to 50% sea-water, or to guarantee an adequate urine production, from 50% sea-water to pure sea-water. It is suggested that when a man is stranded at sea it is not advisable to drink all the fresh water and then be compelled to drink sea-water when dehydrated. It is better to slowly increase the sea-water uptake. This will prolong the time before sea-water needs to be drunk and result in only minor metabolic changes. Return to fresh water will be followed by an immediate return to normal homeostasis. PMID- 2881656 TI - Effect of somatostatin on D-galactose transport across the small intestine of rats. AB - Somatostatin was found to diminish control and theophylline-treated tissue sugar accumulation as well as control and also to diminish theophylline mucosal to serosal D-galactose fluxes. When Na+ was removed from the bath solution, sugar transport was unaltered by the presence of somatostatin. The same results were obtained with phlorizin in the medium. These results seem to suggest that the action of somatostatin is restricted to the Na+-dependent sugar carrier located on the brush border of the intestinal epithelium. PMID- 2881657 TI - Effects of increased energy expenditure on weight gain and adiposity in the LA corpulent rat. AB - Groups of lean or pre-obese LA/N-cp rats were subjected to a program of vigorous exercise (less than 4 hr/day) or remained sedentary from 6 weeks until 12 weeks of age. Sedentary pre-obese rats gained weight twice as rapidly as sedentary lean rats. Exercise treatment resulted in greater decrements in body wt in obese than in lean rats, but did not result in absolute weight loss in either group. At 12 weeks of age, fat pad weights in principle depots were 10-15 times greater in corpulent than in lean rats and were significantly smaller in the exercised groups of both phenotypes, and corresponded with lower relative adiposity compared to corresponding sedentary groups. Heart weights were greater in corpulent than lean, while gastrocnemius muscle weights were similar in both phenotypes. Exercise was without effect on the weight of either muscle tissue in either phenotype. Interscapular brown adipose tissue weights and the IBAT:BW ratio were greater in obese than in lean rats. IBAT weights were lower in exercised than sedentary rats of either phenotype, but the IBAT:BW ratio was lower only in the obese exercised rats. In sedentary rats, L-alpha glycerophosphate dehydrogenase and malic enzyme activity were greater in obese than lean, and exercise treatment resulted in increased L-alpha-glycerophosphate dehydrogenase and malic enzyme only in lean rats. These results are consistent with a redistribution of energy expenditure from energy storing to energy dissipating pathways following vigorous exercise, resulting in slowed rates of weight gain and body fat accretion in both lean and obese animals, with the most significant decrements among pre-obese rats. PMID- 2881658 TI - Rhythmical jaw movements and lateral ponto-medullary reticular neurons in rats. AB - Neuronal activity in the lateral reticular formation was investigated in urethane anesthetized rats. Stimulation of anterior and posterior cortical areas induced two types of rhythmical jaw movements (RJM). The effects of stimulation of these cortical areas, the peripheral nerves, and the trigeminal motor nucleus on these neurons and their activity during the RJM were analyzed. The smallest percentage of neurons receiving anterior cortical input received peripheral input, and most neurons with posterior cortical input received peripheral input. Sixty per cent of reticular neurons showed the rhythmical firing closely related to the RJM. Therefore, these neurons may participate in masticatory pattern formation. PMID- 2881659 TI - Plasma corticosterone in chicks reared under several lighting schedules. AB - Plasma corticosterone was determined by radioimmunoassay in 6-7-week-old male broiler type chicks, reared under several carefully controlled lighting regimes. When subjects were grouped by photoperiod of rearing, chicks reared in darkness had significantly lower hormone levels than diurnal controls, or than subjects reared in continuous light. Around-the-clock sampling revealed a diurnal corticosterone rhythm, with high daytime levels and lower night-time levels. This rhythm appeared to be retained in constant light, although phase shifted or free running. Neither analysis by light intensity level nor by lights on/lights off status at the time of blood sampling revealed differences in plasma corticosterone between the experimental groups which could be attributed to these factors. PMID- 2881660 TI - Hemoglobin transition in the anuran Pelodytes punctatus. AB - In the anuran Pelodytes punctatus the larval hemoglobin produces five electrophoretic bands. In the premetamorphic period, two other bands appear which are typical of the adult. They gradually substitute the larval bands completely as in other anurans. The pathway of the hemoglobin shift indicates that the synthesis of the adult fractions does not depend on the thyroid hormones for its activation, whereas the disappearance of the larval fractions depends on the destruction of the "larval" red blood cell line. As in other species of anurans which are considered primitive, the hemoglobinic change of Pelodytes punctatus starts earlier and develops slower than in other more evolved anurans. In normal developing specimens of Pelodytes punctatus the change in the hemoglobin fractions occurs very slowly and finishes 4 weeks after the metamorphosis, whereas in "hibernated" specimens the rate of change is higher and it ends earlier, probably as a consequence in the retarded larvae, of the increased sensibility of the hemopoietic tissues to the metamorphosis factors. PMID- 2881661 TI - Anaerobic metabolism in fowl embryos during normal incubation. AB - Lactate concentration in blood, liver, yolk, amniotic and allantoic fluid and blood pyruvate was measured in embryos in the final week of incubation. Blood lactate was low up to day 18. The blood lactate/pyruvate ratio and liver lactate increased from day 19 until hatching. From day 14 to 19, lactate concentration in amniotic fluid remained constant, it increased 2-fold in yolk and 10-fold in allantoic fluid. There was only a 48% net accumulation of lactate in the three cavities. In conclusion, fowl embryos do not turn to anaerobic metabolism until the hatching process starts on day 19. PMID- 2881662 TI - On the status of the study of invertebrate neurons in tissue culture--phyla Mollusca and Annelida. AB - The utilization of tissue culture in neurobiological studies is discussed for all phyla phylogenetically preceding Phylum Arthropoda. Only two phyla, Mollusca and Annelida, are represented in such studies. The members of Phylum Mollusca which have been so investigated are Aplysia, Helisoma and Lymnaea. The mollusc Aplysia has been used to investigate several processes, including neurosecretion, synaptic transmission and synaptogenesis. Helisoma was employed to study factors regulating neurite growth and the specificity of synapse formation; mechanisms of neurite growth were investigated in the snail Lymnaea. The only member of Phylum Annelida involved in appropriate studies has been the leech Hirudo. This organism was used to investigate axonal regeneration and synaptic mechanisms. PMID- 2881663 TI - Plasma glucagon and energy substrate responses of domestic fowl to treadmill exercise. AB - Exercise-induced alterations in the concentrations of plasma glucagon-like immunoreactivity (GLI), plasma free fatty acids (FFA) and blood glucose and lactate were measured in separate groups of male and female domestic fowl. There were only small changes in blood glucose and lactate concentrations but plasma FFA and GLI rose by up to 450 and 200% respectively. There was evidence that the GLI response was stronger at higher exercise intensities. It is suggested that the mobilization of FFA for use as energy substrates by the working muscles may be stimulated by the enhanced secretion of glucagon. PMID- 2881664 TI - Water metabolism in free-ranging pine voles (Microtus pinetorum). AB - Rates of body water turnover in free-ranging pine voles exceeded those reported for a large number of similarly sized mammals. Concentrations of urine obtained from free-ranging pine voles were significantly lower than values published for other free-ranging mammals and also for laboratory-maintained members of this species. Rates of body water turnover in this species were not correlated with seasonal changes in soil temperatures. PMID- 2881665 TI - Effect of salt depletion on sodium concentration in serum and urine of Bufo chilensis. Evidences for increased levels of neurohypophysial principles in their plasma. AB - Salt-depleted toads Bufo chilensis were compared with animals maintained in NaCl solution and a control group with respect to Na+ content in serum and urine. Plasma hydro-osmotic activity of the animals was measured by increased water transfer across the isolated urinary bladder of the frog (Caudiverbera caudiverbera). Sodium in serum is not affected by pre-adaptation in distilled water. Urine Na+ is markedly reduced. Plasma from depleted animals increases water transfer across the isolated urinary bladder. Immersion in NaCl solution did not have this effect. An increase in neurohypophysial hormones in the blood of the animals is postulated. PMID- 2881666 TI - Respiration and lactate production in isolated frog skeletal muscle: effects of passive stretch. AB - The effects of varying degrees of passive stretch on in vitro oxygen consumption and intracellular lactate efflux have been investigated in paired recti abdomini muscles from small male frogs. Oxygen consumption [mm3 (STP)/mg (dry wt)/hr] was found to be linearly related to load (r = 0.98), increasing from 1.57 +/- 0.11 (SE) at 2 g to 2.30 +/- 0.18 at 10 g, 2.89 +/- 0.16 at 20 g and 3.26 +/- 0.21 at 30 g. Lactate released into the medium [microM/g (dry wt)/hr] was inversely related to load (r = -0.52), increasing initially from 36.84 +/- 3.28 (SE) at 2 g to 108.55 +/- 12.9 at 10 g, then abruptly decreasing with additional loading (18.10 +/- 2.60 at 20 g and 11.71 +/- 2.80 at 30 g). Results suggest that as stretch-related oxidative energy metabolism increases, there is a lessening dependence on anaerobic energy-yielding processes. PMID- 2881667 TI - Pancreatic hormones in the nonhibernating and hibernating golden mantled ground squirrel. AB - The effects of hibernation on pancreatic insulin, glucagon, somatostatin, and pancreatic polypeptide was investigated in the golden mantled ground squirrel (Citellus lateralis). During hibernation, pancreatic organ weight decreased to 57% of the nonhibernating weight. The content of all four pancreatic hormones during hibernation was significantly reduced. The concentrations of insulin, pancreatic polypeptide and somatostatin, but not of glucagon, were significantly reduced during hibernation. The maintenance of the pancreatic glucagon concentration during hibernation may be related to its role in counter-regulation and carbohydrate homeostasis during fasting. PMID- 2881668 TI - Absorption of electrolytes and water by the jejunum and colon in milk-fed lambs. AB - Net absorption of electrolytes (Na, Cl, K, Ca) and water from ligated loops was studied at various intestinal sites in milk-fed lambs. The unidirectional fluxes of Na across the intestinal mucosa were also investigated using 22Na. Net Na and water absorption in the mid-jejunum were about two-fold higher than in the proximal and distal jejunum and the colon descendens. With the exception of the proximal jejunum, Na and Cl absorption did not differ significantly. The unidirectional Na fluxes in both directions were much higher in the proximal and mid-jejunum than in the distal jejunum and colon descendens. K was also absorbed most efficiently from the mid-jejunum. In the colon descendens mean net K absorption was about zero. Ca absorption in the upper and mid-jejunum exceeded that of the distal jejunum and colon descendens, where the values were close to zero. The results show that in the whole jejunum of young milk-fed lambs net absorptive fluxes of Na, Cl, K, Ca and water occur, whereas the colon descendens appears to play a role only in Na, Cl and water absorption. PMID- 2881669 TI - Comparison of red and white muscle wet weight changed by age, denervation and morbid states. AB - [Na]i, [K]i and wet weight of the extensor digitrum longus (EDL) and soleus (SOL) muscles of 9- and 52-week-old rats were measured for 7 days after sectioning of the sciatic nerve. The changes in wet weight of the EDL and SOL muscles of rats over 52 weeks and those of morbid state rats were also measured. There was no significant difference in wet weights between the EDL and SOL muscles in infant rats, but the EDL muscle became much heavier than the SOL muscle with aging. The decrease in rate of growth of wet weight of the EDL and SOL muscles caused by denervation, was greater in young rats than in mature rats. In addition, the rate of decrease was greater in the SOL muscles than in the EDL muscles in both young and mature rats. The [Na]i increased while [K]i was decreased by denervation, and the net Na+ increase and the net K+ loss were greater in young rats than in mature rats. The changing rate was more remarkable in the EDL muscles than in the SOL muscles throughout the aging process. During DOCA treatment over 4 weeks, the decrease of muscle wet weight was greater in the EDL muscles. The mechanisms which serve to maintain normal muscle wet weight in the SOL muscle after denervation or treatment with DOCA, were discussed. PMID- 2881670 TI - Patterns of spontaneous unit preoptic neurosecretory cell discharges in the rainbow trout, Salmo gairdneri. AB - Extracellular antidromic potentials recorded from the neurosecretory cell body were characterized by the following criteria: constant latency, the ability to follow a high frequency rate of stimulation and the collision test. The latency of the antidromic potentials ranged from 12 to 24 ms (17.46 +/- 3.10 SD) which gave a mean conduction velocity of 0.19 m/s, typical of unmyelinated nerve fibers. Two components could be clearly distinguished in the antidromic potential. A small "A" spike which showed constant latency and a large "B" spike with a variable latency and amplitude. A delay of 6.5 ms between the two spikes could occur and sometimes the "B" spike was blocked leaving only the "A" spike. Four patterns of spontaneous activity seem to emerge: Type I (26% of units, M +/- SD = 0.77 +/- 0.32 sp/s) corresponds to a slow and irregular pattern of activity; Type II (28% of units, M = 1.58 +/- 0.47 sp/s) is hard to classify and may be related to an irregular bursting pattern of activity; Type III (28% of units, M = 2.59 +/- 1.19 sp/s) corresponds to a continuous pattern of activity; Type IV (18% of units) represents a rhythmic pattern of activity with an active phase of about 3 min (M = 2.42 +/- 0.90 min), a silent phase of about 4 min (M = 3.89 +/- 3.02 min) and a maximal frequency of unit discharge in the range 2-18 sp/s. No statistical differences exist for the mean dorsal aortic pressure (DAP) between the four types of neurosecretory cell activity. PMID- 2881671 TI - Insulin metabolism and its effect on blood electrolytes and glucose in the turkey hen. AB - Insulin half-life (T1/2) was determined to be similar between egg-laying and non laying turkey hens, averaging 7.5 vs 8.7 min, respectively. Infused insulin lowered plasma glucose 25% in both groups although the time course of each response was different. Circulating phosphorous decreased 30 min following insulin treatment and returned to preinjection concentrations at the end of sampling. Insulin initiated immediate decreases in plasma calcium and magnesium. It is evident that insulin is involved in electrolyte metabolism as well as glucose metabolism in birds. PMID- 2881672 TI - Metabolic alterations induced by hypoxia in the tortoise heart. Comparison between spongy and compact myocardium. AB - Experiments were performed to check the tolerance to severe hypoxia of the tissue layers (compact and spongy) of the tortoise heart. The animals were subjected to hypoxia (7% O2) at 18 degrees C, 28 degrees C and 38 degrees C for 30, 6 and 2 hr respectively, or to anoxia for 30 hr at 18 degrees C and 2 hr at 38 degrees C. At 18 degrees C the metabolic alterations caused by a 30 hr hypoxia were mild whereas at 28 degrees C and 38 degrees C the cardiac glycogen was depleted, lactate had accumulated and the phosphate creatine and ATP content had decreased. The extent of these metabolic changes was similar in the compact and in the spongy layers of the heart. PMID- 2881673 TI - Electrophysiological and behavioral correlates of sleep in the desert iguana, Dipsosaurus dorsalis Hallowell. AB - The circadian behavior of the desert iguana, Dipsosaurus dorsalis, was investigated on the basis of behavioral observation and electrophysiological recording. D. dorsalis adequately complies with accepted criteria for both behavioral sleep and paradoxical sleep. At 20 degrees C, 12% of the photophase is spent in sleep, 95% of the scotophase is spent in sleep. Paradoxical sleep occurs at all times of the year, but only at temperatures of 20 and 30 degrees C. Amounts of behavioral sleep are affected by both temperature and time of year. Total sleep increases with decreased day length and decreased temperature. Daytime sleep increases with decreased temperature. PMID- 2881674 TI - Insulin-induced changes in membrane potential and 3-O-methylglucose uptake at various external K concentrations in frog skeletal muscle. AB - Insulin induced a hyperpolarization of the membrane and stimulated the 3-O methylglucose (3-O-MG) uptake in frog skeletal muscle. In the present study, the relationship between the insulin-induced changes in the membrane potential and the 3-O-MG uptake was investigated. The stimulatory action of insulin on the 3-O MG uptake was mediated by two different mechanisms. One of them was dependent on the change in the membrane potential and the other was independent of the change in the membrane potential. Both values of the insulin-induced changes in the membrane potential and the 3-O-MG uptake were diminished by increasing the external K concentration. One of the causes for the diminution of the 3-O-MG uptake with a rise of the external K concentration would be the decrease in the magnitude of the insulin-induced hyperpolarization. PMID- 2881675 TI - Nutritional requirements for maintenance of body weight and fat deposition in the long-distance migratory garden warbler, Sylvia borin (Boddaert). AB - Intake of food, protein, fat and carbohydrates and their fecal output and the birds' weights were recorded during different feeding trials with specific nutrient reduced diets in the old-world long-distance migratory garden warbler. The birds' body weights were affected by low dietary protein as well as low dietary fat levels. Low dietary protein and fat levels were associated with significant changes in daily gross and net food intake and in the efficiency of food and nutrient utilization. Birds fed on diets with low nutrient levels for an extended length of time recovered in weight after an initial weight loss. They obviously compensated the restricted nutrient levels primarily by increasing the daily food intake and by changing the efficiency of food and nutrient utilization. Effects of restricted dietary nutrient levels on body weight and adaptation depended on the previous composition of the food. The average daily net fat intake was much higher than the average daily net protein intake, both for maintenance of a constant body weight and for successful regain of weight. The data were further discussed with respect to the role of a fruit diet in omnivorous passerine birds. PMID- 2881676 TI - Barium spikes are generated in the spines of the sea urchin Diadema antillarum. AB - In the presence of calcium, Ba2+ ions, at concentrations as low as 1-2 mM, block the action potentials (a.p.'s) elicited by the electrical stimulation of the primary spines of Diadema antillarum. Lower concentrations of barium (0.1 mM) potentiate the a.p.'s recorded from spines equilibrated with Ca-Free artificial sea water (ASW). Exposure of the spines to a saturated solution of EDTA in Ca free, unbuffered ASW reversibly blocks their electrical activity. Spines blocked by EDTA continue to generate a.p.'s following their equilibration with Ca-free ASW containing 1 mM of Ba2+ ions. The time course of the a.p.'s recorded from spines equilibrated with normal ASW is only slightly affected by the combined action of 15 mM of tetraethylammonium (TEA) and 5 mM of 4-aminopyridine (4-AP). In contrast, the duration of the a.p.'s recorded from spines blocked by EDTA and placed in 1 mM barium is markedly increased by the combined actions of TEA and 4 AP at the above concentrations. We conclude that the Ca-channels of the neurites present in Diadema spines are not, at least qualitatively, an exception with regard to their permeation by Ba2+. The blocking action of low concentrations of these ions, particularly in the presence of calcium, may be explained by the extremely high surface to volume ratio prevailing in neurites with a diameter of only less than 0.1-0.3 micron. PMID- 2881677 TI - Induction of adrenocortical special zone in the male possum (Trichosurus vulpecula). AB - The induction of adrenocortical special zone (S.Z.) by gonadotrophin administration was studied in male brush tailed possums. Castrated males injected with porcine FSH (NIH-FSH-P2) formed well developed S.Z.s, varying in sizes from 5-20% of the gland's volume. Pregnant mare serum gonadotrophin (PMSG) was ineffective. From adrenal homogenates of FSH treated possums incubated with [3H] progesterone the major conversion products were 5 beta-reduced steroid metabolites (72%) and cortisol (4%). The conversion products from adrenals of saline and PMSG treated males were cortisol and corticosterone (65%). Of the ten untreated castrates, one had a well developed S.Z. and two had S.Z.s at an early stage of development. Significant 5 beta-reduction of [3H]progesterone was only found in one animal. The plasma FSH concentrations were in intact males 317 +/- 41 ng rat FSH ml-1 (mean +/- SEM) and in castrates 769 +/- 64. The possible reasons for the lack of spontaneous S.Z. formation in intact males are discussed. PMID- 2881678 TI - Differential effects of two bile salts on ion transport characteristics of teleost intestine. AB - The effects of a dihydroxy and a trihydroxy bile salt on the Na+- and Cl(-) absorbing, goby posterior intestine are quite different. Taurochenodeoxycholate, a dihydroxy bile salt, increases tissue permeability to Cl-, primarily by opening the paracellular shunt pathway. The trihydroxy bile salt taurocholate lacks these effects and may, in fact, decrease tissue permeability. In light of the general structural similarity of these two molecules, a detergent action is considered unlikely and, instead, a more specific (perhaps receptor-mediated) mechanism is suggested. PMID- 2881679 TI - Glucose oxidation and oxygen consumption of isolated guinea pig and muskrat hearts. AB - Glucose in Krebs-Henseleit buffer was presented to isolated Langendorff perfused muskrat and guinea pig hearts that were paced at 240 beats/min. Glucose uptake (amount removed from the perfusion fluid) was 3 times greater in the muskrat hearts than in the guinea pig heart. Glucose oxidation (amount converted to CO2) and oxygen consumption did not differ in the hearts of the two species. When glucose is the only exogenous substrate, isolated muskrat hearts extract more glucose than guinea pig hearts but oxidize similar amounts of glucose and have a similar myocardial oxygen consumption. PMID- 2881680 TI - Thyroid response to ovine thyrotropin challenge in cortisol- and dexamethasone treated rainbow trout, Salmo gairdneri. AB - Cortisol or dexamethasone, administered to rainbow trout (Salmo gairdneri) in the form of intraperitoneal "implants" suspended in hydrogenated coconut oil, had no apparent effect on plasma total thyroid hormone levels, or plasma T3/T4 ratios. The duration of the ovine TSH-stimulated surge in plasma T4 levels was decreased and increased in fish given cortisol and dexamethasone "implants" respectively; plasma T3 levels were not affected by TSH stimulation. The level of steroids administered in the cortisol "implants" elicited a moderate increase in plasma cortisol levels, whereas plasma cortisol levels in the dexamethasone-treated fish were suppressed. The altered levels of plasma cortisol had no apparent effect on HSI, hepatic glycogen or hepatic lipid content. PMID- 2881681 TI - Serum iron, serum ferritin and tissue ferritin during development in ducks. AB - Serum ferritin and tissue ferritin from kidney, heart, small intestine, spleen and liver from ducks during development from 16 to 112 days of age were measured by radioimmunoassay using rabbit anti-duck liver ferritin antibodies and goat second antibody. Serum iron concentration and tissue ferritin iron content are given. Serum ferritin concentration, tissue ferritin and ferritin iron content increase gradually during development. The decrease in all these parameters at 8 weeks of age might be due to molting. PMID- 2881682 TI - Epithelial and pillar cell replacement in gills of juvenile trout, Salmo gairdneri Richardson. AB - Young rainbow trout, Salmo gairdneri (Richardson) were injected intraperitoneally with tritiated thymidine, and killed at intervals between 2 hr and 16 days after inoculation. Labelled epithelial cells were first detected autoradiographically along the base of gill lamellae. Epithelial cells proliferated here and then migrated toward the tips of the lamellae. Uniform labelling along the length of the filaments at the base of lamellae indicated that cells were dividing at a constant rate. Transverse sections of filaments showed that epithelial proliferation was also uniform across the base of the lamellae. The interior of the lamellae often had labelled pillar cells, indicating that these cells also divide. The high intensity of the label in animals killed 16 days after inoculation with tritiated thymidine suggests that division probably occurs slowly, less than once every 16 days. PMID- 2881683 TI - Effects of metamorphosis on water permeability of skin in the salamander, Ambystoma tigrinum. AB - Developmentally associated changes in the pressure driven water permeability of the skin of the salamander Ambystoma tigrinum were measured at 20 degrees C in neotenic (gilled), transitional, and fully transformed adults. Mean values for the hydraulic conductivity of the skin (Lp, X 10(-5) cm.sec-1.ATM-1) were, respectively, 1.54, 0.54 and 0.13. This nearly 12-fold decrease in the H2O permeability coincides with the transition from aquatic to terrestrial life and may be related to the changing role of the skin in water conservation. The increase in hydraulic conductivity is opposite to the decrease in H2O diffusion rates reported by others. We suggest a theoretical basis for the apparently conflicting results. PMID- 2881684 TI - Effects of passive stretch on growth and regression of muscle from chickens of various ages. AB - A non-invasive procedure was used to determine the effect of animal age on the growth response of muscle to passive stretch. Stretch increased patagialis muscle weight 61% in 6-week-old chicks and 34% in 10-month-old chicks, 28-month-old animals had an 18% loss of muscle mass during passive stretch. Removal of the stretch stimulus was followed by a rapid return of patagialis weight to control values in 6-week and 10-month animals, while muscle size of 28-month-old animals had not returned to control levels by 22 days, following removal of the stretch. The stretch-induced changes in muscle wet weight could, in part, be attributed to changes in muscle protein. Total muscle DNA content increased during rapid growth in 6-week- and 10-month-old chickens, and returned to control levels during muscle regression. Muscle hydroxyproline content increased in parallel with increases in muscle mass but did not return to control levels during muscle regression in 6-week-old animals. Results of the present study indicate that there was an effect of animal age on stretch-induced hypertrophy and regression of the patagialis muscle. PMID- 2881685 TI - The effect of various ambient ammonia concentrations on the nitrogen metabolism of carp fry (Cyprinus carpio L.). AB - Authors studied how 125, 375 and 625 micrograms/l amounts of NH4Cl added to the water influenced the ammonia excretion of carp fry with an average weight of 2.4 g, compared to the control. During the course of the experiments the NH4N concentration, the pH and the temperature were measured for three days, twice daily. On the basis of our results the threshold concentration exerting harmful effects on the ammonia household of carp fry (disturbing the normal rate of metabolism in the fishes and decreasing their growth rate) is between 125 and 375 micrograms/l. NH4H (50-100 micrograms/l NH3). The ammonia concentrations exceeding 375 micrograms/l NH4+ (and 100 micrograms/l NH3, respectively) can be regarded as undesirable and harmful in frybreeding fish ponds. With regard to the ambient ammonia, a daily cycle developed in the excretion of ammonia: contrary to the control, a minimum in ammonia excretion was measured in the morning, while a maximum was measured in the afternoon. PMID- 2881686 TI - Comparison of the ability of seven gonadotropin preparations from different mammalian sources to interact with the adenylyl cyclase system in corpora lutea from rabbits and rats. AB - The effects of guanine nucleotides and magnesium (Mg2+) on the interaction of seven different gonadotropin preparations with their rabbit and rat luteal receptors were studied and compared to the ability of these gonadotropins to stimulate luteal adenylyl cyclase activity. In both the rabbit and rat, human chorionic gonadotropin (hCG) and human luteinizing hormone (hLH) were less efficacious than the other gonadotropin preparations in stimulating luteal adenylyl cyclase activity and thus behaved as partial agonists. Addition of 2 mM MgCl2 increased the affinity of the rat luteal receptors for all seven gonadotropins tested, while in the rabbit Mg2+ increased the affinities for porcine, bovine, ovine, rat and rabbit LH but did not significantly alter the affinities for hCG or hLH. In no instance did the addition of 100 microM GTP alter the affinity of the receptor from that observed in the absence or presence of Mg2+. A positive correlation existed for both species between the Kd values calculated from binding experiments and the Kact values obtained in adenylyl cyclase assays suggesting that the specific gonadotropin-binding sites present in rabbit and rat luteal membranes represent receptors which mediate the stimulatory effect of LH. The magnitude of the Mg2+-induced increase in affinity of a given gonadotropin preparation for its receptor was correlated with the efficacy with which that gonadotropin stimulated luteal adenylyl cyclase activity in both the rabbit and rat. PMID- 2881687 TI - Haematological correlates of burrowing in Ctenomys. AB - Haematological parameters related to O2 transport and regulation of acid-base equilibrium were determined for two species of Ctenomys. The oxygen capacity values of Ctenomys blood are similar to those of other fossorial mammals. Ctenomys blood has almost half the number of red blood cells of Rattus blood but the amount of Hb in each blood cell is 2-2.5 times higher. Blood pH is within typical mammalian values. Concentration of inorganic phosphate is higher in Ctenomys than in rats while bicarbonate and protein values are within typical mammalian range. PMID- 2881688 TI - Effect of caponization on central nervous system monoamines in the Japanese quail. AB - Depletion of brain regional norepinephrine (NE), dopamine (DA) after alpha methyl paratyrosine (AMT), and serotonin (5HT) were measured in intact and caponized adult male Japanese quail (Coturnix coturnix japonica). Telencephalon, diencephalon, and cerebellum DA was depleted by AMT treatment, but brain stem was not affected. AMT-induced depletion of NE was greatest in telencephalon, diencephalon, and brain stem of capons. Neither caponization nor AMT affected brain regional 5HT. The results from this work indicate that caponization will affect catecholamine dynamics in brain regions other than the hypothalamus. PMID- 2881690 TI - Agonistic behavior and neurochemistry in grouped Japanese quail. AB - Aggressive behavior and whole brain neurochemistry were measured in stable and unstable pairs of male Coturnix coturnix japonica. Aggressive pecking peaked on day 5 of the daily regrouping regime and returned to a basal level on day 14. Aggressive behavior was associated with increased brain norepinephrine (NE), dopamine (DA), and acetylcholinesterase (AChE) in unstable pairs. Habituation (12 15 days) and DA response to daily regrouping and inanition were inversely related in unstable and stable pairs respectively. Normal whole brain NE increases were attenuated in unstable pairs. PMID- 2881689 TI - Manifestations of social stress in grouped Japanese quail. AB - Physiological manifestations of social stress in stable and unstable (resident and visitor) pairs of adult male Japanese quail (Coturnix coturnix japonica) were compared after 7, 14, 21 and 28 days of regrouping. Unstable pairs had reduced body and relative testes (mg/100 g) weights. Plasma cholesterol was increased significantly in unstable pairs, and adrenal cholesterol was reduced significantly by daily regrouping of unstable pairs. Twelve consecutive days of ACTH treatment (2, 4 or 8 IU/100 g body wt given intramuscularly) to birds in stable pairs induced a decrease in body and relative testes weights. The results were similar to those found in birds subjected to daily regrouping. PMID- 2881691 TI - Reduced noradrenaline turnover in brown adipose tissue of lactating rats. AB - Brown adipose tissue properties as well as noradrenaline turnover in the tissue were determined in 15-day lactating rats and virgin controls. Brown adipose tissue thermogenic activity was reduced in lactating rats as shown by a decrease in weight, cytochrome oxidase activity and mitochondrial GDP-binding. The noradrenaline turnover rate was lower in brown adipose tissue from lactating rats. It is suggested that diminished sympathetic activity in brown adipose tissue may be a major cause of the reduced tissue thermogenic activity during lactation. PMID- 2881692 TI - Sensitivity to electricity in the catfish, Parasilurus asotus. AB - The Japanese catfish (Parasilurus asotus) responded in its respiratory reflex to weak electric field not less sensitively than Gymnarchus niloticus. A sensitivity peak was found at about 1-30 Hz. The threshold voltage gradient of the electroreceptive system was determined to be about 0.05 microV/cm. High sensitivity to electric field fluctuating in low frequency being common to Siluriformes, the role of the sensory systems may be common beyond the difference of habitats among species. PMID- 2881693 TI - Effects of hydrostatic pressure per se (101 ATA) on energetic processes in fish. AB - Nucleotides concentrations (ATP, ADP, AMP) have been measured in brain and muscle of eels exposed to 101 ATA of hydrostatic pressure (HP) for 3 hr. Survival times (ST) and oxygen arterial content (CaO2) have been measured in trouts exposed to HP = 101 ATA. The results show that at HP = 101 ATA, AMP increases (P less than 0.05) and ATP decreases (-12%; NS) in muscle but are not modified in brain; ST values are similar in normoxic and hyperoxic conditions, and CaO2 are similar at 1 ATA and 101 ATA of HP. It is concluded that HP tends to decrease aerobic production of energy. This phenomenon is not due to a failure in O2 transport from ambient medium to the cell but to a possible perturbation of the aerobic cellular processes leading to energy production (Krebs cycle and/or respiratory chain coupled to oxidative phosphorylation. PMID- 2881695 TI - Carbachol contracture of stomach smooth muscle of the newt in calcium-free solution. AB - A small muscle preparation of stomach circular muscle of the newt responded to carbachol (CCh) with a phasic contracture. At 20 degrees C, in Ca-free Ringer solution (+1 mM EGTA), the amplitude of CCh contracture was very rapidly inhibited to less than 10% of that in normal Ringer solution (1.8 mM Ca). The amplitude of this CCh contracture was markedly enhanced with increasing [K]0. CCh contracture in Ca-free Ringer solution was also enhanced after K contracture was induced once in the presence of 1.8 mM Ca, followed by soaking in normal Ringer solution. The amplitude of this enhanced CCh contracture persisted up to about 5 min, following rapid decrease to about 70%, and then gradually decreased to a steady level in Ca-free Ringer solution. This decrease in amplitude was prevented by increasing [K]0 during soaking in Ca-free solution; even when the temperature was elevated from 20 to 35 degrees C during the periods of soaking in Ca-free solution, CCh contracture was inhibited only by about 20% in Ca-free high K solution, whereas in Ca-free or Ca-free low Na (Tris) Ringer solution it was inhibited by more than 50%. PMID- 2881694 TI - The isolation and characterisation of a putative adipocyte precursor cell type from the white adipose tissue of the chicken (Gallus domesticus). AB - The conditions of isolation and culture of a chicken adipose stromal-derived cell strain are described and compared with chicken lung fibroblasts in vitro. The stromal cells accumulated intracellular lipid during the post-confluency culture period, this being by contrast with lung fibroblasts. Much higher levels of intracellular lipid were accumulated by the stromal cells when whole chicken serum or chicken plasma lipoproteins were added to the culture medium. Lipoprotein lipase activity emerged in stromal cells maintained post confluency. This activity was absent from pre-confluent stromal cells and pre- and post confluent fibroblasts. The incorporation of 14C-acetate, 3H-oleic acid and 14C glucose into lipids by the stromal cells exhibited a pattern compatible with a concerted shift in the metabolism of the cells towards lipid storage, particularly in the form of triacylglycerols derived from exogenous fatty acids. It is proposed that, in common with the mammalian species previously studied, the white adipose tissue of the chicken (Gallus domesticus) contains a cell type with properties which allow its preliminary identification as an adipocyte precursor cell capable of adipose conversion in vitro. The confirmation of this proposition is amenable to further investigation. PMID- 2881696 TI - Calcium loading properties of carbachol-sensitive calcium store in calcium depleted stomach smooth muscle of the newt. AB - The amount of carbachol (CCh)-sensitive Ca store, which was loaded during Ca contracture in Ca-depleted stomach smooth muscle of the newt, was estimated from the amplitude of the CCh contracture induced in Ca-free high K solution. This store was loaded to nearly maximum level by simultaneous application of 2.8 X 10( 6)M Ca and 113.5 mM K, while Ca contracture induced at this time was less than 10% in amplitude of control (1.8 mM Ca). When the loading was interrupted after 5 sec of 1.8 mM Ca application, the amplitude of Ca contracture reached nearly its maximum, while the loading of the store was only about 30% of that after 90 sec. Contracture induced by Ca-free high K solution immediately after the brief (10 sec) exposure of the muscle to 1.8 mM Ca was about 50% that of K contracture, while little Ca was observed to be loaded. The [K]0-Ca contracture tension relation and the [K]0-Ca loading relation showed sigmoid and linear characteristics, respectively. PMID- 2881697 TI - Amino acids, including neurotransmitter candidates, in a hair cell-enriched fraction from the lateral line of Xenopus laevis. AB - A hair cell-enriched neuromast fraction from the lateral line of Xenopus laevis was compared with adjacent tactile organ and epidermis for content of primary amine-containing components. Of 32 components quantitated by cation-exchange HPLC with fluorescence detection of orthophthalaldehyde adducts, L-alpha-amino adipic acid, O-phosphoethanolamine, L-alpha-glycerophosphorylethanolamine, O-phospho-L serine, and L-lysine were elevated in concentration in the neuromast relative to the tactile organ an/or epidermis. L-Aspartic acid, L-asparagine, L-glutamic acid, and taurine were present at higher levels in the tactile organ or epidermis than in the neuromast. Taurine was found in only trace amounts in the neuromast. The tactile organ and epidermis contained at least 3 unidentified primary amine components that were absent or reduced in amount in the neuromast. This study demonstrates that the epidermally-derived, hair cell-containing neuromast of the lateral line of Xenopus laevis is different in molecular composition from surrounding epidermally-derived tissue. Such differences may reflect specialized mechanoreceptive function. PMID- 2881698 TI - A comparison of intestinal permeability between humans and three common laboratory animals. AB - Intestinal permeability of humans and three species of experimental animals was assessed by the oral administration of the three non-metabolizable sugars: lactulose, rhamnose and mannitol and collecting all the urine produced in a specified time. The total percentage recovery of the permeability markers was determined by high performance liquid chromatographic assays of urinary aliquots. The permeability of the human gut to mannitol was substantially greater than that of rats, guinea pigs, or hamsters (18-, 6- and 29-fold increases, respectively). The permeability to lactulose in humans was somewhat less than that found in guinea pigs (P less than 0.05), but three times greater than that found in rats or hamsters (P less than 0.001). Human rhamnose permeability was substantially greater than that of rats, guinea pigs or hamsters (6-, 2.5-, and 7-fold increases, respectively). The results suggest that the permeability of the human gut to probe molecules is considerably different from that of three common laboratory rodents, but is closest to that of guinea pigs. Possible species differences in the physiological factors which control permeability are discussed. PMID- 2881699 TI - Hematology of Japanese quail selected for high or low serum corticosterone responses to complex stressors. AB - Blood was collected from random-bred male Coturnix coturnix japonica and from quail selected genetically for high or low serum corticosterone responses to complex stressors after chronic exposure to short daily photoperiods and after exposure to long photoperiods. When compared to the low response quail, high response quail exhibited increased mean cellular hemoglobin values, reticulocyte numbers and heterophil percentages, and decreased monocyte and eosinophil numbers after exposure to long photoperiods. The data indicate that these corticosterone response lines can be partitioned by their hematological responses to photoperiodic manipulation. PMID- 2881700 TI - Reticulocyte numbers in Japanese quail chicks. AB - Erythrocyte parameters in Coturnix coturnix japonica were evaluated daily during the first 2 weeks after hatching. Nadirs in total circulating erythrocyte numbers, hematocrit percentages, and hemoglobin concentrations were found during the first 5 days posthatch. Reticulocytosis from 4 to 9 days posthatch ameliorated these nadirs until 12 days posthatch, when secondary nadirs appeared. Erythropoiesis was indicated by reticulocytosis when hemoglobin levels decreased. Reticulocyte maturation was indicated from 3 to 6 days after the onset of erythropoiesis by the predominance of mature erythrocytes in circulation. PMID- 2881701 TI - Tyrosine aminotransferase of chicken liver: purification and properties. AB - Tyrosine aminotransferase has been purified from chicken liver to homogeneity by a 5-step procedure. The resultant enzyme preparation has a specific activity (256 units activity/mg protein) comparable to results published for the enzyme purified from rat liver and represented an overall recovery of 35-40%. In terms of structure (native and subunit molecular weights, immunological reactivity, and kinetic parameters) (apparent Michaelis constants for L-tyrosine and 2 oxoglutarate, oxoacid specificity, pH optimum) the purified enzyme from chicken liver exhibits remarkable similarities to tyrosine amino-transferase from rat liver. PMID- 2881702 TI - Displacement of zinc and copper from copper-induced metallothionein by cadmium and by mercury: in vivo and ex vivo studies. AB - The in vitro affinity of metals for metallothionein (MT) is Zn less than Cd less than Cu less than Hg. In a previous study Cd(II) and Hg(II) displaced Zn(II) from rat hepatic Zn7-MT in vivo and ex vivo (Day et al., 1984, Chem. Biol. Interact. 50, 159-174). The ability of Cd(II) or Hg(II) to displace Zn(II) and/or Cu(II) from metallothionein in copper-preinduced rat liver (Zn, Cu-MT) was assessed. Cd(II) and Hg(II) can displace zinc from (Zn, Cu)-MT both in vivo and ex vivo. The in vitro displacement of copper from MT by Hg(II) was not confirmed in vivo and ex vivo. Cd(II) treatment did not alter copper levels in (Zn, Cu)-MT, as expected. Hg(II) treatment, however, did not decrease copper levels in MT, but rather increased them. The sum of the copper increase and mercury incorporation into MT matched the zinc decrease under in vivo conditions and actually exceeded the zinc decrease under ex vivo conditions. Short-term exposure of rat liver to exogenous metals can result in incorporation of these metals into MT by displacement of zinc from pre-existing MT. Displacement of copper from pre existing MT by mercury, as predicted by in vitro experiments, was not confirmed under the conditions of our in vivo and ex vivo experiments. This result is explainable based on the differing affinities and/or preferences of the two metal clusters in MT. PMID- 2881703 TI - Biochemical evidence for cholinergic involvement in the Limulus brain. AB - The transport of [3H]choline by the corpora pedunculata of the circumoesophageal ring gland (brain) of Limulus polyphemus was studied. Corpora pedunculata slices were incubated individually in Chao's solution containing 0.01 microM [3H]choline at room temperature (25 +/- 2 degrees C) and readily accumulated the radiolabel from the extracellular environment. The corpora pedunculata uptake of [3H]choline was linear over 60 min. The kinetic analysis indicated the existence of dual uptake systems for choline within the corpora pedunculata, a high affinity choline uptake process (Km = 0.54 microM and Vmax = 0.037 pmoles/mg/min) and a low affinity process (Km = 137 microM and Vmax = 6.3 pmoles/mg/min). The high affinity choline transport system was dependent on sodium ions and was inhibited by micromolar concentrations of hemicholinium-3. The pre-exposure of the corpora pedunculata to Chao's solution containing 90 mM potassium for 15 min resulted in a 24% increase in the velocity of the high affinity choline uptake process (Vmax = 0.046 pmoles/mg/min). The 90 mM potassium Chao's pretreatment stimulated a substantial increase in the synthesis of [3H]acetylcholine by the corpora pedunculata. The results suggest that the high affinity choline uptake process within the Limulus corpora pedunculata is associated with the synthesis of the transmitter acetylcholine, presumably within cholinergic terminals in this tissue. PMID- 2881704 TI - Effect of quinidine and tetrodotoxin on the activation of non-adrenergic nerves in guinea-pig trachealis muscle. AB - Activation of non-adrenergic neurones in guinea-pig trachealis muscle was accomplished by electrical field stimulation and by the neurotoxin aconitine, in the presence of atropine and propranolol. Aconitine (10(-5) M) activated non adrenergic neurones more slowly, but was as efficacious as supramaximal field stimulation (70 V, 1 msec, 1-100 Hz), producing 70-80% of the maximal relaxation to forskolin or theophylline. Quinidine (3 X 10(-5) M-3 X 10(-4) M) and tetrodotoxin (5 X 10(-9) M-3 X 10(-6) M) blocked relaxations to aconitine and field stimulation, without affecting smooth muscle relaxant responses to forskolin. The results suggest that the non-adrenergic inhibitory effects of quinidine are related to its presynaptic local anaesthetic actions, rather than to postsynaptic receptor blockade of the non-adrenergic inhibitory neurotransmitter. PMID- 2881705 TI - A comparative study of high affinity choline uptake and choline utilization in cholinergic and non-cholinergic tissues. AB - Comparative studies of [3H]choline accumulation were done in the Limulus corpora pedunculata, abdominal ganglia and cardiac ganglion. Dual uptake processes for choline were found in all three tissues. In acute experiments, the corpora pedunculata high affinity choline uptake system showed exclusive sensitivity to ouabain. Prolonged exposure to ouabain revealed that the HAChUS of all three tissues were significantly inhibited. The metabolism of [3H]choline transported via the high affinity process in the three tissues was studied. [3H]Acetylcholine was a major product of the [3H]choline taken up by the corpora pedunculata and the abdominal ganglia. Phosphorylcholine was the major product seen in cardiac ganglion extracts and occurred in significant proportions in abdominal ganglia extracts. [3H]Acetylcholine was not detected in cardiac ganglion extracts. Treatment with either lithium chloride or hemicholinium-3 markedly inhibited high affinity uptake of [3H]choline in all three tissues. PMID- 2881706 TI - Dieldrin transformation to photodieldrin in liver and kidney of broiler. AB - Dieldrin, a potent residual insecticide and common contaminant of the environment, is metabolized in liver and kidney of broiler to photodieldrin, a photoisomer of dieldrin. This metabolite has by gas-liquid chromatography (g.l.c.) analysis a retention time different to the aldrin. The analysis by thin layer chromatography (t.l.c.) of metabolite shows an Rf of 0.37. The i.r. (infra red) spectrum shows the band corresponding to the epoxide ring (800-1300 cm-1) and does not show the characteristics bands of C = O (1800 cm-1) and ClC = CCl (1600 cm-1). PMID- 2881708 TI - Distribution of selenium in marine animals: relationship to diet. AB - The chemical form of selenium in the muscle tissues of marine animals in relation to diet has been examined. Inorganic selenium concentrations in all muscle tissues were below the detection limits of the analytical method employed (0.001 mg/kg). Selenium was found to be associated in all tissues predominantly with insoluble proteins. Lipid-soluble and ethanol-soluble selenium constituted less than 18% of the selenium present in tissues and was independent of diet. PMID- 2881707 TI - Localization and synthesis of monoamines in regions of Limax CNS controlling feeding behavior. AB - Localization and synthesis of dopamine and serotonin in the cerebral and buccal ganglia of Limax maximus were studied. A combination of fluorescence histochemistry, immunocytochemistry, and microchemical analysis showed that both amines were localized to particular cell groups and fiber tracts within and between the two sets of ganglia. Since these ganglia control feeding behavior, which is readily modified by associative learning, these studies have direct bearing on analysis of both motor control and learning mechanisms. PMID- 2881709 TI - The action of two classes of pyrethroids on the inhibition of brain Na-Ca and Ca + Mg ATP hydrolyzing activities of the American cockroach. AB - Ca2+-stimulated ATP hydrolyzing activities (i.e. Na-Ca ATP hydrolysis and Ca + Mg ATP hydrolysis) measured in cockroach brain tissue were highly sensitive to the action of pyrethroid insecticides under in vitro conditions. Non-cyano-containing pyrethroids inhibited Na-Ca ATP hydrolysis to a greater extent than their cyano containing counterparts. The reverse is true for pyrethroid action on Ca + Mg ATP hydrolysis. Nonmitochondrial Ca + Mg ATP hydrolysis of disrupted synaptosomes was the most sensitive activity examined. Ca2+-stimulated ATP hydrolyzing activities were inhibited in cockroaches poisoned by permethrin in vivo. In vivo poisoning occurred in the presence of a similar amount of bound [14C]permethrin which had been determined to cause a substantial amount of inhibition to Ca2+-stimulated ATP hydrolyzing activities in vitro. PMID- 2881710 TI - Copper absorption in sheep. AB - Female sheep were used to determine the regions of the gastrointestinal tract able to absorb Cu. Copper was absorbed from the abomasum, small intestine and colon, but not from the rumen-reticulum or caecum. In vitro studies indicated that Cu uptake was linearly related to the Cu concentration. Copper complexed to histidine, lysine or glutamine was absorbed in a similar manner to ionic Cu and at a similar rate. In vitro Cu uptake was not affected by ouabain, rotenone, oligomycin, 2,4-dinitrophenol fluoride or zinc. The in vitro data show that lumen to-mucosal cell Cu transfer has kinetics reflecting simple diffusion rather than a saturable, energy-dependent process. PMID- 2881711 TI - Effect of mosquito killer insecticides on freshwater mussels. AB - The effect of four insecticides (Fyfanon, K-Othrin, Unitox 7 and Unitox 20) was investigated on the freshwater mussels Anodonta cygnea L., Anodonta anatina L. and Unio pictorum L. The studies were performed in hard water (total salinity of 310 mg/l). The LC50 values for 24, 48, 72, 96 hr and 7 days were determined with a static test at 22 degrees C. All the three mussel species proved to be extremely tolerant against the insecticides tested. The effect of sublethal concentrations of these insecticides on the periodic activity of the mussels was also analyzed, comparing the changes of the active and resting periods. In a concentration of 0.1 microliter/l, all the four insecticides affected the periodic activity of U. pictorum, whereas in A. anatina three of them (Fyfanon, K Othrin and Unitox 7) and in A. cygnea two of them (K-Othrin and Unitox 7) evoked alterations. This concentration is lower by three to five orders than those of the LC50 values of 96 hr. PMID- 2881712 TI - Inhibition of trout (Salmo gairdneri R.) PBG-synthase by some metal ions (Mg2+, Pb2+, Zn2+). AB - The effect of metal ions on the activity of trout kidney and liver PBG-synthase was investigated. Heavy metals inhibited the kidney enzyme in a complex manner. Kinetic analysis of the inhibition of liver activity by Pb2+ (Ki = 1.3 mM) was consistent with non-competitive inhibition, whereas Zn2+ (Ki = 1.3 mM) and Mg2+ (Ki = 3.5 mM) were competitive inhibitors. PMID- 2881713 TI - Acute toxicity of copper to mediterranean dogfish. AB - Acute copper toxicity to dogfish (Scyliorhinus canicula) was determined. Median lethal concentrations (LC50) for 24 and 48 hr were respectively 16 and 4 mg/l. These results are compared with those for zinc in dogfish and with the values for copper toxicity in several teleosts obtained by other authors. PMID- 2881714 TI - Metabolism of some carcinogenic aromatic amines in four species of marine sponges. AB - Postmitochondrial fractions from marine sponges Geodia cydonium, Tethya aurantium, Verongia aerophoba and Pellina semitubulosa activate precarcinogenic aromatic amine 2-aminoanthracene, but not precarcinogenic polycyclic aromatic hydrocarbon benzo(a)pyrene, to Salmonella typhimurium TA 98 mutagens. All four sponge species lack a benzo(a)pyrene monooxygenase activity, but possesses the enzyme activity whose characteristics (selective activation of aromatic amines, NADPH-dependency, pH optimum at 8.4) are similar to FAD-containing monooxygenase. Tethya postmitochondrial fraction possesses an UDP-glucuronyl transferase activity which catalyzes the conjugation of a considerable part of metabolized 2 acetylamino [9-14C]fluorene to water soluble glucuronides. The possible ecological significance of exuded aromatic amine metabolites as well as the significance of the presence of the selective potential for the activation of aromatic amines to mutagens among sponges for our understanding of the fate and effects of carcinogens in the marine environment are discussed. PMID- 2881715 TI - Metabolism of copper and zinc in the liver and bone of the perinatal guinea-pig. AB - Hepatic copper concentration in the guinea-pig increased markedly during the second-half of gestation, attaining a maximum shortly after birth; thereafter, concentration declined rapidly during the neonatal period. Changes in perinatal hepatic copper concentrations paralleled the binding of copper to a cytosolic metallothionein-like component, and the loss of hepatic copper in the neonates coincided with increases in serum copper concentrations. Zinc concentrations of the perinatal liver were low and showed no dramatic developmental changes. The humerus showed striking increases in zinc concentration with gestational age, attaining peak concentration before term and a marked depletion of tissue zinc during the neonatal period. PMID- 2881716 TI - Intestinal uptake and retention of copper in the suckling rat, Rattus rattus--IV. Mechanisms of intestinal copper accumulation. AB - Copper-67, administered either parenterally or via the maternal milk, accumulates principally in the intestine and liver of the 6-day-old pup. Most of the 67Cu in the soluble fraction of the intestine is associated with the heterogeneous Cu complex, which is located predominantly in the ileum. The rates of uptake and loss of 67Cu in the liver and intestine indicate that enterohepatic circulation of Cu in the neonate is appreciable. Whilst the concentration of Cu in the bile of the 13-day-old pup is high (16-fold greater than that in the adult male rat), translocation of Cu from both the liver and duodenum to the ileum probably occurs via the blood, rather than by the reabsorption of biliary Cu. Although the Cu complex normally seems to be retained within the distal intestine until the enterocytes are desquamated, Cu in this form is utilized when the Cu-intake of the neonate is restricted. PMID- 2881718 TI - The role of the nervous system in algae-induced gamete release by Mytilus californianus. AB - Algae-induced spawning in M. californianus was associated with an increase in dopamine in the visceral ganglia and a decrease in serotonin in the pedal ganglia. Lesioning studies indicate that nervous communication between the pedal and visceral ganglia plays a major role in gamete release. PMID- 2881717 TI - The uptake and storage of iron and lead in cells of the crayfish (Orconectes propinquus) hepatopancreas and antennal gland. AB - The heavy metals iron and lead are taken up and metabolized in a similar manner by the crayfish hepatopancreas, but only lead appears to enter cells of the antennal gland (green gland). Iron, on the other hand, which apparently is not taken up by the antennal gland cells following systemic injections of low doses (0.05 mg), exerts striking alterations in cell ultrastructure after pericardial injections of massive doses (0.5 mg). Electron microscopic examination and atomic absorption spectrophotometric analyses of the hepatopancreas and antennal glands of iron-injected crayfish revealed that iron was selectively stored in metal containing vacuoles of R- and F-cells in the hepatopancreatic cells, where it accumulated in concentrations that were toxic to these cells. High doses of iron caused alterations in the ultrastructural morphology of the cells of the antennal glands, although no accumulation of iron was apparent. Lead was similarly stored in metal-containing vacuoles of the cells of the hepatopancreas of lead-injected crayfish, but also accumulated in high concentrations (prior to being excreted) in vacuoles, cytoplasmic bodies and vesicles in the cells of the antennal gland. In contrast, lead in high concentrations was relatively non-toxic to any of these cells, suggesting that crayfish were more efficient in detoxifying and eliminating lead than iron. PMID- 2881719 TI - Oxygen uptake and gill morphological alterations in Procambarus clarkii (Girard) after sublethal exposure to lead. AB - The effects of sublethal lead concentrations on the oxygen uptake in whole animals and excised gill of Procambarus clarkii, as well as the gill morphological alterations, were investigated. Oxygen uptake rates of whole crayfish showed a great variability and decreased as the lead concentration increased. Significant differences were not found (ANOVA, P greater than 0.05). Oxygen consumption of excised gills decreased significantly as the lead concentration increased (P less than 0.01). Macroscopic and microscopic observations of the gill filaments of crayfish treated with 200 mg Pb/l indicated a general disorganization. The filaments showed the apices rounded and they appeared grossly blackened. PMID- 2881720 TI - Injections of alpha-melanocyte stimulating hormone affect pineal serotonin, melatonin and N-acetyltransferase activity. AB - To determine if exogenously administered alpha-melanocyte stimulating hormone (alpha-MSH) affects nighttime pineal N-acetyltransferase activity, pineal levels of 5-hydroxytryptophan, serotonin and melatonin, and plasma prolactin levels, adult male hamsters were injected at 1900 hr (lights out 2000-0600 hr) with two doses of the peptide and killed at 0300 hr. The low dose of alpha-MSH (200 ng) produced a significant fall in pineal serotonin, pineal NAT activity and plasma prolactin values. The high dose of the peptide (20 micrograms) increased circulating prolactin titers and pineal serotonin levels and caused a concomitant decrease in pineal melatonin levels. PMID- 2881721 TI - Serotonin induced protein phosphorylation in the Aplysia eye. AB - Serotonin (5-HT) increases the phosphorylation of two low molecular weight phosphoproteins of 23,000 and 15,000 daltons molecular weight and decreases the phosphorylation of a 20,000 dalton phosphoprotein in the isolated Aplysia eye. The cAMP analog 8-benzylthio cAMP increases and decreases the phosphorylation of the 23,000 and 20,000 dalton 5-HT sensitive phosphoproteins, respectively. The effect of 5-HT on protein phosphorylation is not affected by the phase of the circadian rhythm of spontaneous compound action potentials generated in the eye. PMID- 2881722 TI - A comparison of some effects of phosphine, hydrogen cyanide and anoxia in the lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae). AB - The effects of phosphine, hydrogen cyanide and anoxia on levels of ATP, pyruvate and lactate in Rhyzopertha dominica are compared. The effect of phosphine on anaerobiosis is not directly comparable either with HCN or anoxia. Reduction of catalase by feeding 3 amino 1,2,4 triazole does not enhance the toxicity of phosphine in treated insects. PMID- 2881723 TI - The mercury-203 method for evaluating metallothioneins: interference by copper, mercury, oxygen, silver and selenium. AB - Metallothioneins are low molecular weight proteins rich in sulfhydryl groups (cysteinyl) which readily bind various heavy metal cations, e.g. cadmium, copper, gold, mercury, silver and zinc. Mercury has a particular affinity for sulfhydryl groups and mercury-203 has been used as the basis of a rapid, sensitive, radiometric assay for metallothionein. The potential of 16 metals and oxygen for interfering with this test was examined. The mercury-203 test appears to be sensitive to the presence of copper, mercury, oxygen, selenium and silver. PMID- 2881724 TI - Induction of anionic glutathione transferases in rat liver by propylthiouracil. AB - The treatment of rats with propylthiouracil (PTU) resulted in an induction of not only cationic but also anionic glutathione (GSH) transferases. DE-52 column chromatography of the anionic GSH transferases divided into five main peaks (I V). Peaks I-IV had a high activity toward 1-chloro-2,4-dinitrobenzene (CDNB). Peak V, which is a new form of the enzyme, showed high activity to ethacrynic acid. PTU induced peaks I and V, whereas phenobarbital increased the activity of only peak I. PMID- 2881725 TI - The effect of lactic acid and the volatile fatty acids on the aggregation behavior of Periplaneta americana (L.). AB - Young larvae of Periplaneta americana (L.) are attracted to filter paper wetted with 10(-2)-10(-3)% solutions of butyric acid. Other volatile fatty acids and lactic acid, as well as other organic and inorganic acids, are repellent to larvae at high concentrations, and ineffective at low. PMID- 2881726 TI - Biological action of pyrazolopyrimidine derivatives against Trypanosoma cruzi. Studies in vitro and in vivo. AB - The capacity of 54 different pyrazolo(3,4-d) or (4,3-d)pyrimidine derivatives to inhibit Trypanosoma cruzi epimastigote and trypomastigote multiplication, and for some of them its chemotherapeutic activity, was evaluated. Six pyrazolo(3,4 d)pyrimidines showed inhibitory activity against epimastigote forms, 4 aminopyrazolo(3,4-d)pyrimidine being the most active, 5-fold more so than 4 hydroxypyrazolo(3,4-d)-pyrimidine. Neither compound was active against freshly isolated trypomastigotes, suggesting biochemical differences between culture and bloodstream forms of T. cruzi. On both epimastigote and trypomastigote forms, 7 amino-3-beta-D-ribofuranosylpyrazolo-(4,3-d)pyrimidine (FoA) was about 2-fold more active than 7-hydroxy-3-beta-D-ribofuranosylpyrazolo-(4,3-d)pyrimidine (FoB); however, when tested on T. cruzi-infected mice, only FoB exhibited significant chemotherapeutic activity. Previous results suggest that, except for FoB and FoA: (a) pyrazolopyrimidine insensitivity is trypomastigote-specific and (b) drug-insensitivity is lost when trypomastigotes transform into epimastigotes and vice versa. PMID- 2881727 TI - Effects of halothane on feeding motor activity in the snail Lymnaea stagnalis. AB - Snails exposed to the general anaesthetic halothane show an increase in biting plus mouthing movements. Perfusion of the isolated CNS with halothane leads to a period of increased spiking activity, followed by suppression of activity in identified feeding motoneurones in the buccal ganglia. Synaptic inputs to motoneurones from interneurones of the buccal feeding pattern generator are differentially affected. Possible mechanisms underlying the generation of motoneuronal bursting in the presence of halothane are examined. PMID- 2881728 TI - Plasma uric acid levels in ethanol-fed turkey poults treated with allopurinol. AB - Plasma uric acid levels were determined in ethanol-fed poults following administration of allopurinol. In young poults, allopurinol at a dose of 50 mg/kg significantly depressed plasma uric acid levels 6 hr post-dosing. At 11 hr post dosing, plasma uric acid levels were significantly elevated in the allopurinol treated poults when compared with control poults. During a period of ethanol abstinence, allopurinol at a dose of 40 mg/kg significantly depressed plasma uric acid levels up to 8 hr post-dosing. At a dose of 30 mg/kg, plasma uric acid levels were similar to control values at 4 and 6 hr post-dosing. Data suggest that plasma uric acid levels can be depressed in ethanol poults when allopurinol is administered every 8 hr at a dose of 40-50 mg/kg of body weight. PMID- 2881729 TI - Evaluation of allopurinol as a cardioprotectant in ethanol-fed turkey poults. AB - Cardioprotectant effects of allopurinol were investigated in ethanol-fed poults during induction of cardiomyopathy and during a period of ethanol abstinence. In young poults fed ethanol, allopurinol has an additive effect on depression of growth but has little or no effect on caloric consumption. Allopurinol significantly depresses heart weight and heart weight to body weight ratios in young poults. In poults 5 weeks and older, allopurinol depresses significantly body weight and caloric consumption. Although allopurinol depresses heart weight in older poults, it appears to have little or no effect on heart weight to body weight ratios. Cardioprotective effect of allopurinol is more apparent during the inductive process than during the recovery phase. PMID- 2881730 TI - Effects of vagotomy on circulating levels of catecholamines and corticosterone in the pigeon. AB - The effects of bilateral cervical vagotomy on the blood levels of corticosterone, and catecholamines, adrenaline (A) and noradrenaline (NA), in pigeons, were studied. Plasma levels of corticosterone and NA were found to be significantly higher and of A lower, in the vagotomized (VgX) pigeons as compared to their sham operated (VgS) controls. These changes in VgX pigeons are explained as caused mainly by the lack of the vagal tone. PMID- 2881731 TI - Glutathione transferases in aquatic and terrestrial animals from nine phyla. AB - Glutathione transferase (GST) was present in 71 of 72 animal species/stages representing nine phyla when measured with 1-chloro-2,4-dinitrobenzene (CDNB). Our hypothesis that all animals have GST was not falsified. Transferase activity towards ethacrynic acid (ETHA) was present in species from all phyla investigated, but some animals seem to be without this activity. Activity towards 1,2-dichloro-4-nitrobenzene (DCNB) was less developed in aquatic animals than in terrestrial ones. The amount of protein binding to GSH-affinity gel matrix was rather uniform, ranging between 0.3 and 0.7% of soluble protein in homogenates of widely diverse animal species, thus being less variable than the enzyme activity. Transferases active towards DCNB did not bind at all or were less firmly bound to the GSH-affinity gel than the activity towards CDNB or ETHA. Fractionation was obtained by using a gradient of GSH. With SDS-electrophoresis it was demonstrated that the proteins with affinity to GSH had monomers in the MW-range 21.500 29.000. Hydra attenuata had one band (MW = 25,000); all other sources gave a complex pattern with up to six bands. It is concluded that GSTs are characteristic major constituents of animal cells, probably with some common basic function. Mutant forms able to aid detoxication are retained in the phylogenesis when they increase the fitness of the animal. PMID- 2881732 TI - Effects of cadmium and zinc on steroid metabolism and steroid level in the sea star Asterias rubens L. AB - Steroid metabolism was studied in gonads and pyloric caeca of male and female sea stars which had been exposed to cadmium or zinc for 3 weeks. Steroid metabolism had increased in animals exposed to heavy metals. Significant increase of the enzyme activity was observed for 17 alpha-hydroxylase in the pyloric caeca of female animals exposed to zinc (pregnenolone----17 alpha-hydroxypregnenolone) or cadmium (progesterone----17 alpha-hydroxyprogesterone), for 17 beta hydroxysteroiddehydrogenase in the gonads of female animals (dehydroepiandrosterone----androstenediol) and in pyloric caeca of male animals (androstenedione----testosterone) after exposure to cadmium, and for 5 alpha reductase (progesterone----5 alpha-pregnane-3,20-dione) in ovaries of cadmium exposed sea star. There is some evidence that pregnenolone metabolism in male and female animals is affected by zinc in a different way. The effect of cadmium on the esterification of androstenedione differed highly significantly among male and female animals. It was concluded that the main way of entrance of cadmium into sea stars is via the surrounding medium and not via the food consumed. Testosterone and progesterone levels in, respectively, gonads of female and pyloric caeca of male sea stars which had been exposed to cadmium were significantly higher than the corresponding values in control animals. The effect of zinc exposure on testosterone level in pyloric caeca is significantly different for both sexes. Cadmium interacts directly with the esterification of testosterone, strongly stimulating this process. Cadmium stimulates the production of testosterone by action at the level of the biosynthesis of 17 beta hydroxysteroiddehydrogenase. PMID- 2881733 TI - Effects of forskolin, isoproterenol and lithium ions on leucophores of a teleost, Oryzias latipes: evidence for involvement of adenylate cyclase in pigment dispersion response. AB - Forskolin, a stimulator of adenylate cyclase, induced a dose-dependent and reversible dispersion of pigment within fish leucophores. Li+, known as an inhibitor of the enzyme, depressed pigment-dispersion response of leucophores to either forskolin or isoproterenol, inducing an aggregation of pigment within the cells. These results indicate that Li+ acted on the cells through inhibition of forskolin- or isoproterenol-stimulated adenylate cyclase activity. The results suggest that adenylate cyclase is involved in the pigment-dispersion response of leucophores and that cAMP acts as a second messenger in the response. PMID- 2881734 TI - The influence of cholecystokinin, vasoactive intestinal peptide and secretin on pancreatic and biliary secretion in laying hens. AB - White Leghorn hens, 14-29 weeks old, were surgically fitted with cannulas for collecting pancreatic and biliary secretions, and a jugular cannula for continuous infusion of either cholecystokinin (CCK), vasoactive intestinal peptide (VIP), or secretin. As compared to secretory levels during saline infusion, CCK significantly stimulated biliary flow and biliverdin concentration in bile; VIP significantly depressed biliverdin concentration but enhanced bicarbonate secretion in both pancreatic and biliary secretions, and also increased total pancreatic flow. Secretin depressed biliary flow and increased pancreatic bicarbonate release. The principal hormonal regulator of biliary secretion appears to be CCK, and that of pancreatic secretion to be VIP. PMID- 2881736 TI - Dementia. AMA Council on Scientific Affairs. PMID- 2881735 TI - Misinformation regarding behavior therapy. PMID- 2881737 TI - Venomous coelenterates. PMID- 2881738 TI - Campylobacter infection masquerading as ulcerative colitis. AB - A 24-year-old woman noted erythematous tender nodules on her extremities and temporal areas while being treated for Campylobacter-positive colitis. Histologic examination showed groups of inflammatory cells in the subcutaneous tissue and dermis around pilosebaceous follicles and sweat glands. The diagnosis of nonspecific, chronic dermatitis and panniculitis was made. The cutaneous lesions improved with the administration of tetracycline, Azulfidine, and adrenocorticotropic hormone, after which a negative culture for Campylobacter was obtained. Campylobacter colitis may stimulate ulcerative colitis. PMID- 2881739 TI - Direct visualization of the sites of DNA methylation in human, and mosquito chromosomes. AB - Human and mosquito fixed chromosomes were digested with restriction endonucleases that are inhibited by the presence of 5-methylcytosine in their restriction sites (Hha I, Hin PI, Hpa II), and with endonucleases for which cleavage is less dependent on the state of methylation (Taq I, Msp I). Methylation-dependent enzymes extracted low DNA amounts from human chromosomes, while methylation independent enzymes extracted moderate to high amounts of DNA. After DNA demethylation with 5-azacytidine the isoschizomers Hpa II (methylation-dependent) and Msp I (methylation-independent) extracted 12-fold and 1.4-fold amounts of DNA from human chromosomes, respectively. These findings indicate that human DNA has a high concentration of Hpa II and Msp I restriction sites (CCGG), and that the internal C of this sequence is methylated in most cases, while the external cytosine is methylated less often. All the enzymes tested released moderate amounts of DNA from mosquito chromosomes whether or not the DNA was demethylated with 5-azacytidine. Hpa II induced banding in the centromere chromosome regions. After demethylation with 5-azacytidine this banding disappeared. Mosquito DNA has therefore, moderate to high frequencies of nonmethylated CpG duplets. The only exception is the centromeric DNA, in which the high levels of C methylation present produce cleavage by Hpa II and the appearance of banding. Centromere regions of human chromosomes 1 have a moderately low concentration of Hpa II-Msp I restriction sites. PMID- 2881740 TI - Evolution of Y chromosomal lampbrush loop DNA sequences of Drosophila. AB - The evolutionary conservation of Y chromosomal DNA sequences of Drosophila hydei in different species of the genus Drosophila was studied by in situ hybridization and on genomic DNA blots of restriction enzyme digested DNA. We demonstrated that Y specific DNA sequences, which form major parts of lampbrush loops related to the male fertility genes, are only retained in a few closely related species during evolution. Other Y chromosomal DNA sequences, also present in lampbrush loops but with homology to autosomal and X chromosomal locations, were found in distant species. We propose a model for the evolution of the Y chromosomal lampbrush loops. PMID- 2881741 TI - Significance of eosinophil and mast cell counts in rectal mucosa in ulcerative colitis. A prospective controlled study. AB - Eosinophil and mast cell counts were done in 44 patients with active ulcerative colitis, 10 patients with ulcerative colitis in remission, and 44 matched subjects with functional bowel disorder. Mean (+/- SD) rectal eosinophil counts (EC) per unit area were significantly high (P less than 0.01) in active ulcerative colitis (5.80 +/- 5.49) as compared with inactive disease (2.81 +/- 2.19) or controls (3.01 +/- 1.67). Eosinophil count was not significantly different in the acute stage between responder (6.36 +/- 5.95) and nonresponders (5.1 +/- 5.84) to medical treatment and was thus of little discriminatory and prognostic value. Mean (+/- SD) EC was reduced from 6.36 +/- 5.95 to 3.91 +/- 3.19 in responders after four weeks of medical treatment. There was little change in the EC with treatment in nonresponders. No correlation was seen between tissue eosinophils and clinical severity of ulcerative colitis. Mast cell count was not significantly different between patients with active ulcerative colitis, inactive disease, and controls and thus had little diagnostic or prognostic value. It can be concluded therefore, that EC in the rectal mucosa indicated activity but not severity of ulcerative colitis. A reduction in EC possibly indicated remission. Rectal EC, however, cannot correctly prognosticate the treatment response and outcome of the disease. PMID- 2881742 TI - Bovine and human cDNA sequences encoding a putative benzodiazepine receptor ligand. AB - cDNAs containing the entire coding sequence of endozepine, a putative ligand of the benzodiazepine receptor, were isolated from bovine and human cDNA libraries. These libraries were constructed using a novel oligonucleotide adapter molecule that allowed us to combine the use of G/C tailing with the preservation of the unique Eco RI site in the vector, lambda gt10. The amino acid sequences derived from these cDNA clones are identical to those previously determined for the purified proteins and are homologous to a related rat protein termed diazepam binding inhibitor. The endozepine proteins are highly conserved, as illustrated by the finding that the nucleotide sequences of the coding regions are 93% conserved between the bovine and human forms. Analysis of these sequences indicates that endozepine is not, as expected, derived from a precursor molecule containing a transient signal peptide. Moreover, Northern analyses using the cloned cDNAs as hybridization probes indicate that the 650-nucleotide endozepine mRNA is expressed in a number of peripheral tissues in addition to brain. These observations may be consistent with a recent report describing the presence in peripheral tissues of benzodiazepine receptors on the outer mitochondrial membrane (Anholt et al., 1986). In addition to the endozepine cDNAs, we also isolated a bovine cDNA clone which encodes a larger protein, a portion of which is homologous to endozepine. This related protein may be synthesized in a precursor form containing putative signal peptide and membrane-spanning domains. PMID- 2881743 TI - [The role of steric characteristics of the gangliolytic molecule in its interaction with cholinoreceptor]. PMID- 2881744 TI - Bromobenzene metabolism in the rat and guinea pig. AB - The metabolism of bromobenzene was studied in the rat and guinea pig with respect to three considerations: the dose and species dependence of 3-bromophenol excretion; the formation of methylthio analogs of dihydrodiols and catechols; and the identification of acidic bivalent sulfur metabolites. In the guinea pig, 3 bromophenol was the major monohydric phenolic metabolite under conditions of both relatively low and relatively high dosage. In the rat, 3-bromophenol and 4 bromophenol were formed in approximately equal amounts. 2-Bromophenol was a minor metabolite in both species. Methylthio analogs of dihydrodiols were found as guinea pig, but not rat, metabolites. Two di(methylthio)dihydroxytetrahydrobromobenzene metabolites were excreted by the rat but not by the guinea pig. These methylthio compounds have not been reported in earlier studies of bromobenzene metabolism. In the guinea pig, the acidic urinary metabolites were a mercaptoacetate, a mercaptolactate, and a mercapturate. In the rat, the acidic metabolites were a mercapturic acid and premercapturic acids. This species difference in urinary acids indicates a difference in acetylation/deacetylation processes for cysteine conjugates. PMID- 2881745 TI - Disposition and biotransformation of quinpirole, a new D-2 dopamine agonist antihypertensive agent, in mice, rats, dogs, and monkeys. AB - The disposition and metabolism of quinpirole were studied in rats, mice, dogs, and monkeys. A single 2 mg/kg dose of 14C-quinpirole was administered orally to rats, mice, and monkeys. Dogs were given a single 0.2 mg/kg iv dose of 14C quinpirole. Of the dose administered, 75-96% was recovered in the urine within 72 hr, with the majority being excreted during the first 24 hr. Peak plasma concentrations of radioactivity and quinpirole were coincident and were observed within 0.25 hr in rodents and at 2 hr in monkeys. Unchanged quinpirole accounted for 0.9%, 36%, and 69% respectively. Biotransformation of quinpirole was compared by quantitating the urinary metabolites by HPLC. The percentage of the radioactivity in urine representing unchanged drug was determined for each species: monkey (3%), dog (13%), mouse (40%), and rat (57%). The majority of 14C quinpirole was shown to be biotransformed in rats, mice, and monkeys through common metabolic pathways but to various extents. Most metabolites resulted from structural alterations (N-dealkylation, lactam formation, omega and omega-1 hydroxylation) that centered around the piperidine ring portion of the molecule. These metabolites were less important in dogs. The major metabolic pathway in dogs involved hydroxylation of a methylene carbon adjacent to the pyrazole nucleus of quinpirole followed by O-glucuronidation. Evidence of metabolism of the pyrazole moiety was found in the isolation of an N-glucuronide conjugate of quinpirole from monkey urine. PMID- 2881746 TI - Characterization of the induction of cytosolic and microsomal epoxide hydrolases by 2-ethylhexanoic acid in mouse liver. AB - When mice were exposed to 1% 2-ethylhexanoic acid in the diet, cytosolic and microsomal epoxide hydrolase (EC 3.3.2.3) activities were increased maximally (2 2.5- and 0.5-1-fold, respectively) after 3 days. Immunochemical quantitation of these enzymes indicated that the process involved was a true induction in both cases. Maximal levels of peroxisome proliferation (as indicated by carnitine acetyltransferase activity) were obtained after 7 days of exposure. All three of these activities returned to control levels within 4 days after termination of the treatment. The liver somatic index was slightly increased after 4 days of administration of 1% 2-ethylhexanoic acid, but the protein contents of the "mitochondrial," microsomal, and cytosolic fractions were unaffected. The activity of peroxisomal palmitoyl-CoA beta-oxidation was increased 2-fold, whereas peroxisomal catalase activity was unaffected. Exposure to 2-ethylhexanoic acid also increased cytochrome oxidase activity, suggesting an effect on mitochondria. Other parameters of detoxication--i.e. total microsomal cytochrome P-450 content, cytosolic glutathione transferase activity toward 1-chloro-2,4 dinitrobenzene, and the "cytosolic" epoxide hydrolase activity localized in the "mitochondrial" fraction--were not affected by 4 days of treatment with 1% 2 ethylhexanoic acid. PMID- 2881747 TI - Mechanisms of lidocaine kinetics in the isolated perfused rat liver. I. Effects of continuous infusion. AB - The mechanisms of time-related reduction in lidocaine clearance were studied using a "one-pass" perfused rat liver system. Lidocaine was infused continuously for a period up to 150 min (concentration ranged from 9.6 to 278 microM). The time required for lidocaine to achieve steady state in the effluent ranged from 20 to 90 min. Analysis of material balance suggested that capacity-limited tissue binding was partially responsible for determining the time to steady state. The characteristic rise of monoethylglycinexylidide to a maximum within 5 min and decline to a stable level during constant lidocaine infusion suggested that the deethylation pathway may be partly deactivated. This observation could be the major determinant for the time-dependent effects of lidocaine elimination. Saturation of metabolism, mainly hydroxylation, and product inhibition by monoethylglycinexylidide did not reduce the extraction of lidocaine significantly. The dose-related reduction in lidocaine elimination is believed to have little contribution to the time effects of lidocaine. PMID- 2881748 TI - Deacetylation of diltiazem by rat liver. AB - The enzyme system mediating the hydrolysis of the calcium antagonist diltiazem to give deacetyldiltiazem was characterized in the rat. Tissue distribution studies showed that the highest level of activity was mainly localized in the microsomal fraction of the liver. Some activity was also detected in the red blood cells. The kinetics of the enzymatic reaction demonstrated that the formation of deacetyldiltiazem increased linearly with time up to 60 min and with protein content up to 7.8 mg. Apparent Km and Vmax values calculated from a Lineweaver Burk plot were 0.17 X 10(-3) M and 0.013 mumol/mg of protein/min. Mercuric chloride, silver nitrate, and cupric chloride at concentrations of 0.6 X 10(-3) M decreased the diltiazem deacetylase activity to 47%, 24%, and 19%, respectively, as compared to control incubations. At a concentration of 6.7 X 10(-8) M, cadmium sulfate decreased the hydrolysis of diltiazem by 40%, whereas cobaltous sulfate at concentrations of 10(-3) M did not affect the deacetylation activity. The hydrolysis reaction was depressed by the organophosphorus compounds, bis-p nitrophenylphosphate and diisopropyl fluorophosphate to 31% and 0%, respectively, at concentrations of 10(-6) M. Eserine sulfate at a concentration of 2.2 X 10(-4) M, and disulfiram and aspirin at concentrations of 10(-3) M decreased the diltiazem deacetylase activity to 17%, 71%, and 79%, respectively. Rifampicin and phenacetin at concentrations of 10(-3) M did not inhibit the hydrolysis reaction. In vivo pretreatment of the rats with phenobarbital increased the in vitro diltiazem deacetylase activity 3.2-fold, whereas 3-methylcholanthrene did not affect the enzymatic hydrolysis of diltiazem. PMID- 2881749 TI - Plasma concentration-response relationship for cimetidine inhibition of drug metabolism in the rat. AB - Cimetidine inhibition of antipyrine elimination has been studied in the rat over a range of steady state cimetidine concentrations. Cimetidine is a potent inhibitor of antipyrine metabolism with a concentration of about 1.25 mg/liter causing a 50% decrease in the total plasma clearance of antipyrine. The degree of inhibition of antipyrine clearance caused by cimetidine is dependent upon its plasma concentration, but the relationship is not linear. The formation clearances of all antipyrine metabolites measured--3-hydroxymethylantipyrine, 4 hydroxyantipyrine, and norantipyrine--are inhibited by cimetidine at all concentrations used. The susceptibility of the different metabolites to cimetidine inhibition does vary. The renal clearance of antipyrine was also decreased by cimetidine by an unknown mechanism. Analysis of the individual formation clearances suggests that the inhibition of oxidative metabolism due to cimetidine is caused by its binding to two classes of enzyme sites--a high affinity, low capacity and a low affinity, high capacity site. These two different sites would appear to be responsible for the production of different metabolites of antipyrine. The true nature of the selectivity of cimetidine inhibition of antipyrine metabolism is apparent from the formation clearances but not from the urinary metabolite patterns. PMID- 2881750 TI - Comparison of adenosine 3'-phosphate 5'-phosphosulfate concentrations in tissues from different laboratory animals. PMID- 2881751 TI - Influence of age on intrinsic clearance of bupivacaine and its reduction by cimetidine in elderly male rats. PMID- 2881752 TI - Effect of surgery on serum alpha 1-acid glycoprotein concentration and serum protein binding of DL-propranolol in phenobarbital-treated and untreated rats. PMID- 2881753 TI - Mechanisms of lidocaine kinetics in the isolated perfused rat liver. II. Kinetics of steady state elimination. AB - The steady state kinetics of lidocaine and its metabolites were modeled using nonlinear elimination pathways for multiple enzymes. The main metabolites, monoethylglycinexylidide and 3-hydroxy-lidocaine, were infused in the absence of lidocaine to measure the kinetic parameters for secondary elimination. Data from continuous perfusion of lidocaine in the isolated perfused rat liver at concentrations ranging from 9.6 to 278 microM (N = 16) were used to calculate the kinetic parameters for formation of the main metabolites. The elimination of lidocaine in the liver was approximated by the well stirred model. The whole liver study gave higher elimination rates than were predicted from microsomal studies. The major pathways for elimination of lidocaine in the rat were deethylation and hydroxylation, and subsequent elimination along these pathways accounted for the poor material balance at low dosage levels. The observed competitive inhibition of hydroxylation was in agreement with the predictions of the model. PMID- 2881754 TI - Mechanisms of lidocaine kinetics in the isolated perfused rat liver. III. Evaluation of liver models for time-dependent behavior. AB - Three models for the elimination of lidocaine in the isolated perfused rat liver were used to simulate the time course of both lidocaine and its metabolites in a single-pass perfusion system: well stirred, parallel tube, and a two-compartment model to test the effects of enzyme heterogeneity. All models included multiple enzymes and multiple metabolic pathways, as well as varying degrees of tissue binding. Although the well stirred and parallel tube models gave qualitatively different results, neither model predicted that the concentration of monoethylglycinexylidide would pass through a maximum and then decline to a lower steady state value, as observed in continuous perfusion experiments. Although each of the three models tested would give reasonable agreement with steady state observations, the test of the time-dependent behavior of both lidocaine and monoethylglycinexylidide was more discriminating. Each model gave characteristic predictions for the time course of the metabolites. PMID- 2881755 TI - The series-compartment model for hepatic elimination. AB - An empirical model is presented for hepatic elimination of substrates which treats the liver as a series of compartments. The number of compartments serves as an adjustable parameter and determines the effect of changes in blood flow on elimination. By allowing variable dependence of clearance on blood flow, the model serves as a bridge between the extreme cases of venous equilibrium (the "well-stirred" model) and the "parallel-tube" model. The adjustable parameter in the model can be determined by measuring the clearance at different rates of blood flow, or at different extents of binding of the substrate to blood components. Examples are given for steady state elimination of several different substrates with linear and nonlinear elimination kinetics. PMID- 2881756 TI - Microsomal metabolism of pyrrolizidine alkaloids from Senecio jacobaea. Isolation and quantification of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine and N oxides by high performance liquid chromatography. AB - The metabolism in vitro of four pyrrolizidine alkaloids from the poisonous plant Senecio jacobaea was studied. The pyrrolizidine alkaloids jacobine, jacoline, senecionine, and seneciphylline, all macrocyclic diesters of retronecine, were incubated with rat liver microsomes. Analysis of incubation extracts by HPLC with a PRP-1 reverse phase styrene-divinylbenzene resin column revealed the presence of two major metabolites, 6,7-dihydro-7-hydroxy-l-hydroxymethyl-5H-pyrrolizine and an N-oxide derivative. Mass spectrometry was used to confirm the structure of metabolites isolated by preparative HPLC using the PRP-1 column and a C-8 reverse phase column. Quantitative HPLC analysis using the PRP-1 column allowed the comparison of the rates of formation of the dihydropyrrolizine derivative and N oxides from the four alkaloids. PMID- 2881757 TI - The formation of procainamide hydroxylamine by rat and human liver microsomes. AB - A method is described, using HPLC and electrochemical detection, which permits the direct quantitation of procainamide hydroxylamine. Procainamide hydroxylamine was formed from procainamide by hepatic microsomes from both rat and human, with rat microsomes showing higher apparent formation rates. The apparent Km for formation of procainamide hydroxylamine was 0.044 mM for rat liver microsomes, with an apparent Vmax of 2.81 nmol/min/mg of protein. Estimates of Km from three human microsomal samples were 6.29, 2.89, and 6.88 mM. Vmax estimates were 0.31, 0.74, and 0.74 nmol/min/mg of protein, respectively, roughly an order of magnitude less than that observed for the rat. Microsomal formation in both species was inhibited by boiling the microsomes, eliminating NADPH from the incubation system, by preincubation with SKF 525A, cimetidine, or n-octylamine, or by gassing the microsomal incubation mixture with carbon monoxide. These observations suggest that procainamide hydroxylamine formation is cytochrome P 450 mediated. Procainamide hydroxylamine could not be detected in the blood of rats treated with a single dose of procainamide, 100 mg/kg, po. One potential reason for the inability to detect this metabolite in blood is indicated by the rapid disappearance in vitro of procainamide hydroxylamine added to whole blood. Most of this disappearance appears to be due to an interaction with hemoglobin. PMID- 2881759 TI - Effect of diffusional barriers on drug and metabolite kinetics. AB - Previous experimental and simulation studies have alluded to the presence of a diffusional barrier for enalaprilat, the polar, dicarboxylic acid metabolite of enalapril, entering hepatocytes. The present study examined the roles of diffusional clearances of drug and metabolite on the distribution and elimination characteristics in liver. The hepatic intrinsic clearances for enalapril (26.1 ml/min) and enalaprilat (0.7 ml/min), found in a previous study, were used for simulation because, along with their given diffusional clearances (75 and 2 ml/min, respectively), they yielded a high extraction ratio for drug (E = 0.86) and a poor extraction ratio for the preformed metabolite (E = 0.05). While maintaining the intrinsic clearances and hepatic blood flow rate (10 ml/min) constant, only drug and metabolite diffusional clearances were altered. The liver was modeled as three (blood, liver tissue, and bile) compartments, with blood flowing into sinusoids of uniform length L. Blood (sinusoidal) and tissue concentrations of drug and generated and preformed metabolites, at any point x along L and under linear kinetic conditions, were approximated numerically by computer simulations and expressed as the length-averaged or mean concentrations. The factors underlying drug and metabolite (preformed and generated) concentrations, hepatic clearances and elimination rates, and their interrelationships were illustrated graphically, emphasizing the roles of diffusional clearances for drug and metabolite on their spatial distributions and elimination in liver. PMID- 2881758 TI - Studies on the pharmacokinetics and metabolism of 4-chlorodiphenyl ether in rats. AB - The metabolic disposition of 14C-labeled 4-chlorodiphenyl ether ([14C]4-CDE) was examined in rats following iv administration of a single dose (850 nmol/kg). [14C]4-CDE decayed rapidly from the blood since no unchanged [14C]4-CDE was detected in the blood beyond 2 hr after [14C]4-CDE administration. The dispositional kinetics of [14C]4-CDE in rats were best described by a two compartment open pharmacokinetic model. Total radioactivity was excreted slowly from rats; about 41% and 33% of the administered dose were excreted into the urine and feces, respectively, within 1 week after chemical administration. About 5% of the total radioactivity administered to rats was excreted into the bile in 1 hr. The bulk of the radioactivity in the excreta was due to the presence of [14C]4-CDE metabolites. 14C-labeled 4'-hydroxy-4-CDE was the major metabolite and accounted for at least 90% of the radioactivity in the urine. The metabolic conversion of [14C]4-CDE to 14C-labeled 4'-hydroxy-4-CDE was corroborated by in vitro studies with liver microsomes of rats. In addition, [14C]4-CDE was converted by liver microsomes to reactive metabolites which bound irreversibly to microsomal protein. An arene oxide is suggested as the intermediate metabolite in the biotransformation of [14C]4-CDE by rats. PMID- 2881760 TI - Cytochrome P-450 isozymes 2 and 5 in rabbit lung and liver. Comparisons of structure and inducibility. AB - Rabbit cytochrome P-450 isozymes 2 and 5 were purified from pulmonary and hepatic microsomal preparations. Purification of isozyme 5 was monitored by immunochemical methods so that contamination by isozymes 2, 4, and 6 could be avoided. Partial proteolysis of hepatic and pulmonary isozyme 5 showed minor differences in peptide formation when analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and visualized by the silver staining method. In contrast, identical patterns were observed when the peptides were transferred to nitrocellulose paper and visualized immunochemically. The differences observed between the results obtained with the two methods was apparently caused by differences in small amounts of contaminants present in both preparations. HPLC profiles of peptides formed by treatment of pulmonary and hepatic isozyme 5 with trypsin appeared to be the same. In addition, it was found that the pulmonary and hepatic isozymes had identical sequences for the first 20 NH2-terminal amino acids. Three distinct fractions of hepatic cytochrome P-450 isozyme 2 were obtained when chromatography on DEAE cellulose was used as the final step in the purification procedure. In contrast, only a single fraction of purified pulmonary isozyme 2 was isolated by the same method. Analysis of the pulmonary and three hepatic preparations of isozyme 2 by partial proteolysis and visualization of peptides by silver staining or immunoblotting showed no differences. Analysis of tryptic digests by HPLC also produced the same results for each of the four preparations. The first 24 NH2 terminal amino acids were identical for all four preparations of isozyme 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881761 TI - Extrahepatic expression of N-acetylator genotype in the inbred hamster. AB - The genetic control of S-acetylcoenzyme A (AcCoA)-dependent N-acetyltransferase activity (EC 2.3.1.5) was investigated in liver, intestine, kidney, and lung cytosols derived from homozygous rapid acetylator (Bio. 87.20), heterozygous acetylator (Bio. 87.20 X 82.73/H F1), and homozygous slow acetylator (Bio. 82.73/H) Syrian inbred hamsters. AcCoA-dependent N-acetyltransferase activity was highest in hepatic cytosol, followed by intestine, kidney, and lung cytosol. In each of these tissues, cytosolic N-acetyltransferase exhibited an acetylator genotype-dependent activity with highest levels in homozygous rapid, intermediate levels in heterozygous F1 progeny, and lowest levels in homozygous slow acetylators. The ratio of N-acetyltransferase activity between acetylator genotypes was in general substrate dependent but not tissue dependent. Acetylator genotype-dependent N-acetyltransferase activity differences were highest for p aminobenzoic acid, followed by p-aminosalicylic acid, 2-aminofluorene, and beta naphthylamine. Expression of isoniazid N-acetyltransferase activity in each tissue was acetylator genotype independent. Determination of Michaelis-Menten kinetic constants in each tissue suggested that p-aminobenzoic acid N acetyltransferase activity was acetylator genotype-dependent because of catalysis by an isozyme(s) that is both an apparent Km and a Vmax variant. In contrast, the acetylator genotype-independent expression of isoniazid N-acetyltransferase activity in each tissue appeared to result from a common isozyme(s) present in each tissue with equivalent kinetic constants in the two phenotypes. These data suggest that acetylator genotype-dependent expression of AcCoA-dependent N acetyltransferase activity in extrahepatic tissues may play an important role in hereditary predisposition to toxicity and/or carcinogenesis in extrahepatic organs following exposure to arylamine drugs and foreign chemicals. PMID- 2881762 TI - Metabolism of the beta-carbolines, harmine and harmol, by liver microsomes from phenobarbitone- or 3-methylcholanthrene-treated mice. Identification and quantitation of two novel harmine metabolites. AB - This study extends an investigation of the metabolism of the beta-carbolines, harmine and harmol, by untreated, phenobarbitone-induced, or 3-methylcholanthrene (MC)-induced mouse liver microsomes to identify two MC-inducible metabolites of harmine and to quantitate their rates of formation using 3H-labeled substrate. An HPLC system was devised to separate harmine and its metabolites. The major metabolite with MC-induced microsomes was identified by mass spectroscopy and by NMR to be 6-hydroxy-7-methoxyharman and was produced at an initial reaction rate of 11 nmol/min/mg of microsomal protein (27-fold induction). The other novel metabolite, 3- or 4-hydroxy-7-methoxyharman (the position of the hydroxyl group could not be definitively assigned by NMR) was produced at an initial reaction rate of 3.8 nmol/min/mg of microsomal protein (32-fold induction) which was similar to the rate of formation of the other metabolite, harmol, determined previously. All three metabolites were further metabolized to unidentified metabolites. Protein binding of [3H]harmine and [3H]harmol was measured and shown to be metabolism dependent. It was also noted that the alkali conditions used for optimal extraction stimulated the protein binding. PMID- 2881763 TI - Stereochemical aspects of the glutathione S-transferase-catalyzed conjugations of alkyl halides. AB - (R,S)-2-iodooctane and (R,S)-2-bromooctane were found to be substrates for the glutathione S-transferases from rat liver. The conjugation reactions of the enantiomeric 2-halooctanes and glutathione were found to proceed with inversion of configuration at the chiral carbon of the substrate. Selective titration of the free cysteine residues of the glutathione S-transferases provided no observable effect on the stereochemical course of these conjugation reactions. No evidence for substrate stereoselectivity was observed. The diastereomeric S-(2 octyl)glutathiones were produced in approximately equal amounts from racemic 2 halooctane substrates. With S-(+)-2-iodooctane as the electrophilic substrate, a biphasic double reciprocal plot of glutathione concentration vs. initial velocity of product formation was observed suggesting complex kinetics. The S-2 octylglutathione diastereomers were found to be potent inhibitors of the glutathione S-transferase-catalyzed conjugation of 1-chloro-2,4-dinitrobenzene. These results provide support for a single displacement mechanism for the conjugation of 2-halooctanes and glutathione catalyzed by the glutathione S transferases with product inhibition at low glutathione concentrations. PMID- 2881765 TI - Microbial transformation of the antihistamine pyrilamine maleate. Formation of potential mammalian metabolites. AB - Fourteen fungi were found to metabolize pyrilamine (2-[(2-dimethylaminoethyl)(p methoxybenzyl)amino]pyridine). Two Cunninghamella elegans strains transformed essentially all of the pyrilamine added after 144 hr. After 48 hr of incubation, C. elegans ATCC 9245 metabolized 76% of the antihistamine into methylene chloride extractable pyrilamine metabolites. These organic-soluble metabolites were isolated by HPLC and the major metabolites were characterized by comparison of their chromatographic, mass, and 1H-NMR spectral properties with those of authentic compounds. The major metabolite was identified as 2-[(2 dimethyloxyaminoethyl)(p-methoxybenzyl)amino]pyridine (N-oxide derivative of pyrilamine). Other metabolites identified were 2-[(2-dimethylaminoethyl)(p hydroxybenzyl)amino]pyridine, 2-[(2-methylaminoethyl)(p methoxybenzyl)amino]pyridine, and 2-[(2-methylaminoethyl)(p hydroxybenzyl)amino]pyridine. These metabolites represent O-demethylated, N demethylated, and O- and N-demethylated derivatives of pyrilamine, respectively. The mutagenic activities of the N-oxide and the N- and O-dealkylated pyrilamine derivatives, and pyrilamine maleate were measured by reversion of Salmonella typhimurium strains TA97, TA98, TA100, and TA102. Pyrilamine maleate and the three microbial metabolites showed no appreciable mutagenic activity in any of the S. typhimurium tester strains. The metabolism of pyrilamine by 12 other filamentous fungi and yeast strains was much less when compared to C. elegans and ranged from 3.8% to 12.2%. The fungal metabolism of pyrilamine may be useful in predicting results of mammalian metabolism and in readily providing sufficient quantities of metabolites for further toxicological studies. PMID- 2881764 TI - Comparative metabolism and disposition of 1-chloro- and 3-chloro-2-methylpropene in rats and mice. AB - A recent 2-year carcinogenicity study found that gavage administration of 3 chloro-2-methylpropene (CMP), containing 5% 1-chloro-2-methylpropene (dimethylvinyl chloride, DMVC), caused forestomach neoplasms in rats and mice. Similar chronic studies revealed that DMVC caused forestomach neoplasms in both rats and mice; neoplasms of the nasal and oral cavities were observed in rats but not in mice. In the current studies we have investigated the metabolic basis of these differences. Daily doses of 150 mg/kg of 2-[14C]DMVC or 2-[14C]CMP were administered to rats for 1, 2, or 4 consecutive days. One daily dose of 150 mg/kg of DMVC was administered to mice. Both DMVC and CMP were rapidly metabolized; however, CMP was cleared at a slightly lower rate. Rats exhaled approximately 25 and 10% of the DMVC and CMP as CO2, respectively. Mice exhaled 25% of the DMVC as CO2. Rats expired 30% of the administered DMVC unchanged in the 24 hr after dosing compared to only 7% of the administered CMP. Mice expired 5% of the administered DMVC in the same time period. This observation may explain the occurrence of tumors in the nasal and oral cavities of rats treated with DMVC but not in rats treated with CMP or in mice treated with DMVC in 2-year carcinogenicity studies. The 24-hr urinary excretion in rats was 35% of the administered DMVC compared to 58% of CMP. Mice excreted 47% of the administered DMVC in 24 hr in the urine. An unusual urinary metabolite of DMVC, 2-amino-6 methyl-4-thia-5-heptene-1,7-dioic acid, was identified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881766 TI - Toxicology of tremorgenic mycotoxins, fumitremorgin A and B. PMID- 2881767 TI - A review of the pharmacokinetics and efficacy of emesis, gastric lavage and single and repeated doses of charcoal in overdose patients. PMID- 2881768 TI - Phosphoenolpyruvate carboxykinase as a selective indicator of ochratoxin A induced nephropathy. PMID- 2881769 TI - Evaluation of nephrotoxicity using isolated nephron segments. PMID- 2881770 TI - The use of kidney epithelial cell line (LLC-PK1) to study aminoglycoside nephrotoxicity. PMID- 2881771 TI - Postnatal alterations in cerebellar GABA content, GABA uptake and morphology following exposure to carbon monoxide early in development. AB - Rats were exposed to either 0, 75, 150 or 300 ppm carbon monoxide (CO) from the day of conception until 10 days after birth. Exposure to CO resulted in significant deficits in cerebellar weight and deficits in total cerebellar content of gamma-aminobutyric acid (GABA) among rats at 10 days and 21 days after birth. Total cerebellar high-affinity 3H-GABA uptake was decreased among rats exposed to 300 ppm at 21 days of age, while total high-affinity 3H-glutamate uptake was unaffected. Moreover, cerebella of rats exposed to 300 ppm had fewer fissures, although major fissures were of normal depth, when examined histologically at 21 days of age. These results identify developmental processes involving GABAergic neuronal maturation and foliation of the cerebellum as vulnerable to early CO exposure. PMID- 2881772 TI - [Modification of orocecal transit time of salazosulfapyridine by atropine and metoclopramide in healthy probands]. AB - The first appearance of sulpharyridine in plasma was investigated in nine healthy informed male volunteers. In a three way crossover design 6 g salazopyrin alone, together with metoclopramide (0.3 mg/kg i.m.) or atropine (0.01 mg/kg i.m.) were given. Sulphapyridine appears in the blood at the (means +/- S means) 6.2 h +/- 0.8 h (range: 3-11 h) in controls. Together with metoclopramide the first appearance is 3.6 h +/- 0.7 h (range: 2-8 h) and together with atropine these values are 8.1 +/- 0.8 h (range: 6-12 h). The differences are significant with p less than 0.05. The results show the pharmacological modification of motility in the gastrointestinal tract and in consequence the usefulness of salazopyridine to determine the transit time. PMID- 2881773 TI - Mechanisms of calcitonin-induced growth hormone (GH) suppression: roles of somatostatin and GH-releasing factor. AB - Calcitonin (CT) binds to specific receptors in the hypothalamus and has been localized in the pituitary, suggesting a potential neuroendocrine role for this peptide. We and others have previously shown that CT given centrally markedly suppresses pulsatile GH secretion. However, the mechanism mediating this response remains to be elucidated. In the present study, we assessed the involvement of the two hypothalamic GH-regulatory peptides, somatostatin (SRIF) and GH-releasing factor (GRF), using a combination of in vivo and in vitro techniques. Six-hour GH secretory profiles were obtained from eight groups of freely moving rats bearing chronic intracerebroventricular (icv) and intraatrial cannulae. In four groups, salmon (s) CT (250 ng/10 microliters) was administered icv, whereas the remaining four groups received either normal saline (NS) icv or sCT iv. Central injection of sCT caused a severe suppression in amplitude of spontaneous GH pulses compared to NS icv-treated control rats, whereas the same dose of sCT iv had no significant effect. Passive immunization of sCT icv-injected rats with a specific antiserum to SRIF failed to restore the amplitude of GH pulses to normal values. In addition, in vitro basal and 50 mM K+-stimulated SRIF release from incubated hypothalamic fragments was not altered by sCT in doses ranging from 10(-10) to 10(-6) M. The iv administration of a bolus of rat GRF (1-29)NH2 (1 microgram) 1 h after sCT icv injection also failed to augment plasma GH levels compared to sCT iv-treated rats (16.6 +/- 10.0 vs. 326.6 +/- 63.6 ng/ml; P less than 0.001) and NS icv controls (407.2 +/- 145.4 ng/ml; P less than 0.01). Blood calcium levels decreased similarly 1 h after iv and icv sCT administration. These results demonstrate that: sCT inhibits pulsatile GH secretion via a central nervous system site of action, GH suppression induced by sCT is apparently not due solely to increased hypothalamic SRIF release, and centrally administered sCT produces an acute loss of responsiveness of somatotrophs to GRF, which can be dissociated from peripheral blood calcium levels. PMID- 2881774 TI - Protein degradation in skeletal muscle during experimental hyperthyroidism in rats and the effect of beta-blocking agents. AB - beta-Blocking agents are increasingly used in the management of hyperthyroid patients. The effect of this treatment on increased muscle protein breakdown in the hyperthyroid state is not known. In the present study, experimental hyperthyroidism was induced in rats by daily ip injections of T3 (100 micrograms/100 g BW) during a 10-day period. Control animals received corresponding volumes of solvent. In groups of rats the selective beta-1-blocking agent metoprolol or the nonselective beta-blocker propranolol was infused by miniosmotic pumps implanted sc on the backs of the animals. Protein degradation was measured in incubated intact soleus and extensor digitorum longus muscles by determining tyrosine release into the incubation medium. The protein degradation rate in incubated extensor digitorum longus and soleus muscles was increased by 50-60% during T3 treatment. Metoprolol or propranolol did not influence muscle protein breakdown in either T3-treated or control animals. The results suggest that T3-induced increased muscle proteolysis is not mediated by beta-receptors, and muscle weakness and wasting in hyperthyroidism might not be affected by beta blockers. PMID- 2881775 TI - Pharmacological manipulations of alpha-adrenoceptors in the infant rat and effects on growth hormone secretion. Study of the underlying mechanisms of action. AB - The aim of this study was to evaluate whether in infant rats, as in adult rats, the brain adrenergic mechanisms regulate plasma GH levels and, if so, to determine the contribution of GH-releasing hormone (GHRH) and/or somatostatin (SS) pathways. In 10-day-old rats, activation of alpha 2-adrenoceptors by clonidine (CLO) was effective to stimulate GH release starting from 50 micrograms/kg ip and up to 450 micrograms/kg ip, though no dose-related effect was evident. Conversely, alpha 2-adrenoceptor blockade by yohimbine (YOH, 10 mg/kg, ip) decreased baseline GH levels. Administration of methoxamine (METHOX, 10 micrograms/rat, ip), a alpha 1-adrenoceptor agonist, significantly reduced plasma GH concentrations, while prazosin (5 mg/kg BW, ip), a specific alpha 1 adrenoceptor antagonist, stimulated plasma GH secretion. Administration of an anti-SS serum (SS-ab, 300 microliters, ip) induced a significant rise in plasma GH levels, while administration of an anti-GHRH serum (GHRH-ab, 100 microliters, ip) was associated with a striking fall in GH levels. In rats pretreated with SS ab, administration of CLO induced a further rise in plasma GH levels. GHRH-ab significantly reduced plasma GH levels, and this effect was not altered by subsequent CLO administration. Administration of SS-ab and YOH resulted in plasma GH levels intermediate between those of rats treated with SS-ab alone or YOH alone, while pretreatment with GHRH-ab induced a lowering of plasma GH greater than when YOH was given alone. in rats pretreated with SS-ab, the GH-lowering effect of METHOX was completely lacking, while GHRH-ab and METHOX induced a lowering of plasma GH similar to that ensuing after METHOX alone or GHRH-ab alone. Administration of prazosin in rats pretreated with SS-ab did not elicit any further rise in plasma GH, while combined administration with GHRH-ab elicited a GH-lowering effect comparable to that elicited by GHRH-ab alone. These data demonstrate that in the infant rat: brain adrenergic mechanisms involved in the neural regulation of GH secretion are operative; different neuropeptide mechanisms mediate the effect of activation or inhibition of alpha 1- and alpha 2 adrenoceptors. In particular, activation of alpha 2-adrenoceptors stimulates GH secretion via endogenous GHRH release, although a mechanism operating to inhibit hypothalamic SS release cannot be excluded; stimulation of alpha 1-adrenoceptors is inhibitory to GH secretion exclusively via an increased release of hypothalamic SS. PMID- 2881776 TI - Somatostatin-14-like antigenic sites in fixed islet D-cells are unaltered by cysteamine: a quantitative electron microscopic immunocytochemical evaluation. AB - Exposure of somatostatin cells to cysteamine (CSH) produces a marked reduction in somatostatin-14-like immunoreactivity (S-14 LI) in cell extracts. In the present study we have evaluated the effects of CSH on S-14-like sites in fixed islet D cells using immunofluorescence and quantitative electron microscopic immunocytochemistry. Monolayer cultures of rat islet cells exposed to CSH (10 mM) for 1 h and subsequently extracted in 1 M acetic acid exhibited a severe reduction in S-14 LI from 6.6 +/- 0.48 to 0.7 +/- 0.06 ng/dish. CSH-induced reduction in S-14 LI persisted when cells were fixed in Zamboni's solution for 16 h and subsequently extracted and assayed. By immunofluorescence, however, the relative numbers of somatostatin-positive cells as well as the fluorescent intensity were identical in control and CSH-treated cells. CSH did not produce any identifiable abnormality in the ultrastructural appearance of D-cells. Protein A-gold labeling of the islet cells showed a uniform distribution of gold particles in both control and CSH-treated cultures. The density of gold particles over D-cell secretory granules from CSH-exposed cultures (36.6 +/- 3.5 particles/micron2) was not different from that in control D-cell granules (42.2 +/- 5.9 particles/micron2). These data clearly indicate that despite a profound reduction by CSH of S-14 LI in tissue extracts, there is no detectable decrease in the same antigenic sites in tissue sections when assessed immunocytochemically. PMID- 2881777 TI - Control of aldosterone production by angiotensin II is mediated by two guanine nucleotide regulatory proteins. AB - The involvement of guanine nucleotide regulatory proteins in the steroidogenic response of the adrenal glomerulosa to angiotensin II (AII) was investigated by analyzing the effects of Bordetella pertussis toxin (PT) on several aspects of AII action. These included receptor binding, stimulation of aldosterone production and GTPase activity, inhibition of cAMP production, and attenuation of the aldosterone response at high angiotensin concentrations. Pretreatment of glomerulosa cells with PT abolished the inhibitory effects of both AII and somatostatin (SRIF) on ACTH-stimulated cAMP production. Under the same incubation conditions, the stimulation of aldosterone secretion by submaximal and maximal steroidogenic concentrations of AII was completely unaffected by the toxin. However, the attenuation of steroid responses seen with supramaximal concentrations of AII was abolished. In addition, the ability of SRIF to inhibit AII-stimulated steroid production was markedly reduced by PT treatment. The binding of [125I]AII to high affinity sites in intact cells and particulate fractions, and modulation of the binding by guanine nucleotides, were unaffected by toxin pretreatment, even under conditions where a 40-41K protein was completely ADP ribosylated. In contrast, the toxin substantially diminished the binding of [125I]Tyr0-SRIF to SRIF receptors in glomerulosa cells (by 50% after 5 h and by 90% after 20 h). These results indicate that Ni or a similar protein probably mediates the inhibition of cAMP formation by AII and the attenuation of the steroid response by high concentrations of AII as well as the inhibitory actions of SRIF in the adrenal glomerulosa cell. Furthermore, the lack of effect of PT on AII binding and stimulation of GTPase activity suggests the existence of an additional pertussis-insensitive guanine nucleotide-regulatory protein that is activated by lower concentrations of AII and mediates the stimulation of aldosterone production. PMID- 2881778 TI - [Thyrotropin-binding inhibitory immunoglobulins G in thyroid gland cells in patients with Graves-Basedow disease. Clinical studies]. PMID- 2881779 TI - [Thyrotropin-binding inhibitory immunoglobulins G in thyroid gland cells in patients with Graves-Basedow disease. II. Various methodologic aspects of their analysis]. PMID- 2881780 TI - Introduction of human chromosome 11 via microcell transfer controls tumorigenic expression of HeLa cells. AB - Both tumorigenic segregant HeLa X human fibroblast hybrids and tumorigenic HeLa (D98/AH-2) cells can be converted to a non-tumorigenic state following introduction of a single copy of a fibroblast t(X;11) chromosome. The translocated chromosome contains approximately 95% of the 11 chromosome and the q26-qter portion of the X chromosome which contains the hypoxanthine guanine phosphoribosyl transferase (HPRT) gene. Introduction of a human X chromosome has no effect on tumorigenic expression. Suppression of tumorigenicity is relieved by selecting cells which have lost the t(X;11) chromosome by growth in medium containing 6-thioguanine (6-TG). Further, reintroduction of the t(X;11) chromosome into tumorigenic 6TGR cells again suppresses tumorigenicity. Thus, the introduction of a single copy of a human chromosome 11 is sufficient to completely suppress the tumorigenic phenotype of HeLa cells and is suggestive of the presence of tumor-suppressor gene(s) on this chromosome. PMID- 2881781 TI - Sequence conservation in the protein coding and intron regions of the engrailed transcription unit. AB - Engrailed (en) is a gene involved in proper segmentation of the Drosophila embryo. The predicted en protein contains a homeodomain and regions rich in polyalanine, polyglutamine, polyglutamate/aspartate and serine. We have taken an evolutionary approach to define which regions may be of fundamental importance by examining the D. virilis genomic sequence homologous to the D. melanogaster en primary transcription unit. Sequence homology begins at the first ATG of a long open reading frame yielding proteins of 584 and 552 amino acids for the D. virilis and D. melanogaster proteins, respectively. The predicted amino acid sequence can be divided into conserved and non-conserved domains. The C-terminal 30% of the protein (which includes the homeodomain) is completely conserved. In the N-terminal 70% of the protein, the overall conservation is 71%, but non conservative amino acid changes occur in clusters and there are short stretches of highly conserved sequence. A region rich in glutamate and aspartate is conserved and has homology to an 18-amino acid sequence present in members of the myc family of proteins. Major differences in the size of the two proteins occur in regions of non-conserved repeated sequences. In the introns of the engrailed transcription units there are long stretches of conservation, suggesting this DNA may be of functional importance. PMID- 2881783 TI - Processing and metabolism of neuropeptides. PMID- 2881782 TI - Yeast mitochondrial ATPase subunit 8, normally a mitochondrial gene product, expressed in vitro and imported back into the organelle. AB - Subunit 8 of yeast mitochondrial F1F0-ATPase is a proteolipid made on mitochondrial ribosomes and inserted directly into the inner membrane for assembly with the other F0 membrane-sector components. We have investigated the possibility of expressing this extremely hydrophobic, mitochondrially encoded protein outside the organelle and directing its import back into mitochondria using a suitable N-terminal targeting presequence. This report describes the successful import in vitro of ATPase subunit 8 proteolipid into yeast mitochondria when fused to the targeting sequence derived from the precursor of Neurospora crassa ATPase subunit 9. The predicted cleavage site of matrix protease was correctly recognized in the fusion protein. A targeting sequence from the precursor of yeast cytochrome oxidase subunit VI was unable to direct the subunit 8 proteolipid into mitochondria. The proteolipid subunit 8 exhibited a strong tendency to embed itself in mitochondrial membranes, which interfered with its ability to be properly imported when part of a synthetic precursor. PMID- 2881784 TI - Studies on Mg2+-dependent ATPase in bovine adrenal chromaffin granules. With special reference to the effect of inhibitors and energy coupling. AB - The Mg2+-ATPase activities of bovine adrenal chromaffin granules were studied in highly purified preparations of granule ghosts and in intact organelles. The overall ATPase activity (150-250 nmol ADP min-1 mg-1) of the granule ghost preparations was inhibited less than 5% by the bathophenanthroline chelate of Fe(II), a potent inhibitor of mitochondrial F1-ATPase. This small inhibition can be accounted for by a very minor contamination with mitochondria or mitochondrial fragments. The overall ATPase activity of native granule ghosts was inhibited about 75% by N-ethylmaleimide, with half-maximal inhibition at about 20 microM. The titration curve was slightly shifted towards higher concentrations as compared to the inhibition curve for the proton pump activity, which was completely inhibited at 25 microM. N,N'-Dicyclohexylcarbodiimide inhibited the overall ATPase activity by 75-80% at 1.1 mumol/mg protein, a concentration that completely abolished the proton pump activity. Low concentrations (10 microM) of vanadate inhibited the overall ATPase activity by about 15% but had no effect on the proton pump activity, which was partly inhibited only at higher vanadate concentrations. Our attempts to assign a function to the vanadate-sensitive and N ethylmaleimide-insensitive ATPase have so far been unsuccessful. In particular, our assay for ATP diphosphohydrolase activity was negative, although the chromaffin granule ghosts revealed a low Mg2+-ADPase activity (11.8 nmol AMP min 1 mg-1 protein). In intact chromaffin granules the specific Mg2+-ATPase activity (50-70 nmol ADP min-1 mg-1) was stimulated 2-fold by uncouplers, as compared to 1.6-1.7-fold in granule ghosts. The degree of energy coupling was rather independent of the external pH (6.5 less than pH less than 8.0) and temperature (20-45 degrees C). As expected, partial inhibition (about 15%) of the overall ATPase activity by 10 microM vanadate increased the ATPase control ratio. ADP was found to be a potent inhibitor of the proton pump activity with MgATP as the substrate, and the effect can partly be explained by a competitive type of inhibition of the hydrolytic reaction. This effect of ADP explains some of the kinetic data reported for MgATP-dependent (H+-ATPase-dependent) reactions in this organelle, notably the energy-dependent accumulation and storage of catecholamines. PMID- 2881785 TI - Unstable angina revisited once more. PMID- 2881786 TI - Adrenaline infusion evokes increased thromboxane B2 production by platelets in healthy men: the effect of beta-adrenoceptor blockade. AB - The effects of direct adrenergic stimulation, achieved by 60-min adrenaline infusion (0.1-0.2 microgram kg-1 min-1), on thromboxane B2 (TxB2) production by platelets in whole blood ex vivo and on ADP-induced platelet aggregation were studied in seven healthy male volunteers. The effects of two beta-adrenergic blocking agents, pindolol and practolol, on the adrenaline-induced changes were furthermore analyzed. Adrenaline administration resulted in an about ten-fold elevation in plasma adrenaline, and an about three-fold increase in TxB2 production by platelets at 30 min of infusion. The increased TxB2 production persisted throughout the entire adrenaline infusion, and up to 30 min of postinfusion period (recovery). Pindolol blunted markedly the effects of adrenaline on platelet TxB2 production, whereas practolol seemed to have only a weak effect. The sensitivity of platelets to ADP-induced aggregation did not change during the 60 min of adrenaline infusion. However, at 60 min of recovery the platelets showed a significantly increased sensitivity to ADP. Correspondingly, pindolol treatment did not affect platelet sensitivity during the infusion period, but at 60 min of recovery it had caused a significantly decreased sensitivity of platelets to ADP-stimulation. Plasma-free fatty acids increased markedly during the adrenaline infusion. This increase was totally blocked by pindolol, but only partly by practolol. The present results demonstrate that adrenaline, at plasma levels seen for example, in complicated myocardial infarction, stimulates platelet TxB2 production and increases the sensitivity of platelets to ADP after the infusion. Pindolol, but not practolol, inhibits these adrenaline-induced changes in platelet behaviour. PMID- 2881787 TI - Stimulation of hepatic efflux and turnover of glutathione by methionine in the rat. AB - The effect on hepatic glutathione (GSH) turnover of transpeptidation of substrate amino acids by gamma-glutamyl transferase (GGT) was evaluated in intact rats. The infusion of 5 mmol kg-1 of L-methionine, L-cysteine and glycylglycine promptly stimulated hepatic GSH turnover as measured by acetaminophen probe analysis. This stimulation was abolished by pretreatment of the animals with inhibitors of GGT. Glycine and phenylalanine, two amino acids that are poor substrates for transpeptidation by GGT, had no effect on GSH turnover. A methionine load led to a decrease in hepatic GSH from 6.40 +/- 0.6 to 4.1 +/- 0.4 mumol g-1 and significantly increased the plasma clearance of GSH from 4.76 +/- 0.09 to 6.05 +/ 0.36 ml min-1 100g bw-1. In the in situ perfused rat liver increasing concentrations of methionine in the perfusate stimulated the efflux of GSH from 19.5 nmol min-1 g liver-1 without added methionine to 34.1 and 56.3 nmol min-1 g liver-1 at 0.1 and 1.0 mM methionine, respectively. We conclude that the administration of amino acids or dipeptides that are good substrates for transpeptidation by GGT increases hepatic turnover of GSH. The stimulation of sinusoidal efflux of GSH by methionine indicates that an increased efflux is responsible for the increased rate of turnover of hepatic GSH. The associated increase in the plasma clearance of GSH suggests that by increasing the efflux of GSH the liver may provide more GSH for the extracellular transpeptidation of substrate amino acids. PMID- 2881788 TI - Acute systemic and renal haemodynamic effects and long-term antihypertensive action of cadralazine in patients pretreated with beta-blockers and diuretics. AB - The antihypertensive effects of the hydralazine-related compound cadralazine (2 (3-[6-(2-hydroxypropyl)ethylamino]pyridazinyl)ethyl carbazate, ISF 2469), were investigated in 16 patients with primary hypertension concurrently treated with beta-blockers and diuretics. The protocol included a double-blind placebo controlled haemodynamic evaluation after the first tablet and two 4-week double blind placebo controlled cross-over periods followed by an open evaluation during 2 months. Cadralazine induced a moderate, prolonged fall in blood pressure that was associated with vasodilatation and slight increases in cardiac output (dye dilution) and heart rate. Renal plasma flow (PAH) and glomerular filtration rate (51Cr-EDTA) were not significantly influenced, but the filtration fraction was reduced. Plasma concentrations of noradrenaline and adrenaline rose, whereas plasma renin activity was unchanged. The haemodynamic parameters were not correlated with the plasma concentrations of cadralazine. During chronic cadralazine treatment the supine blood pressure was significantly lower than during the double-blind placebo phase (160/93 vs 174/102 mmHg). The compound was generally well tolerated but the body weight increased slightly (1.1 kg), probably because of fluid retention. Several patients who had previously experienced side effects with hydralazine, including one with hydralazine syndrome, tolerated cadralazine well. This suggests that cadralazine does not cross-react with hydralazine. PMID- 2881789 TI - Mediation of the discriminative stimulus properties of 8-hydroxy-2-(di-n propylamino) tetralin (8-OH-DPAT) by the putative 5-HT1A receptor. AB - Male Sprague-Dawley rats were trained to discriminate the putative 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) from saline in a 2-lever operant drug discrimination paradigm. The 8-OH-DPAT cue was found to be highly selective; neither the 5-HT receptor agonists, quipazine, LSD, MK 212 and RU 24969, the 5-HT releasing agent, p-chloroamphetamine, nor the alpha 2 adrenoceptor agonist, clonidine, were able to substitute for 8-OH-DPAT in tests of generalization. In contrast, both buspirone and TVX Q 7821, which like 8-OH DPAT have high affinity and selectivity for the 5-HT1A recognition site, generalized to the 8-OH-DPAT cue in a dose-dependent manner. The discriminative stimulus properties of 8-OH-DPAT were not antagonized by the 5-HT2 receptor antagonist, ketanserin, or the selective beta 1- and beta 2-adrenoceptor antagonists, betaxolol and ICI 118.551, indicating that neither 5-HT2 receptors, nor beta-adrenoceptors play a significant role in the behaviour. However, the 8 OH-DPAT cue was antagonized stereoselectively by pindolol and alprenolol, which have relatively high affinity and stereoselectivity for 5-HT1, but not 5-HT2, recognition sites. Similarly, the capacity of TVX Q 7821 to generalize to the 8 OH-DPAT cue could be blocked by pindolol. In view of the fact that 8-OH-DPAT has negligible affinity for the 5-HT1B site, the above results are consistent with its discriminative stimulus properties being mediated by the putative 5-HT1A receptor. Moreover, agonist activity at central 5-HT1A receptors may be an important mechanism contributing to the anxiolytic properties of buspirone and TVX Q 7821. PMID- 2881790 TI - Evidence for low brain penetration by the H1-receptor antagonist temelastine (SK&F 93944). AB - Competition by the potent selective H1-receptor antagonist temelastine (SK & F 93944) with [3H]mepyramine binding to mouse cortex H1-receptors has been measured in vitro and vivo. The data were compared with that obtained using the classical H1-receptor antagonists mepyramine and promethazine and indicated that temelastine has relatively low ability to penetrate the blood-brain barrier compared with the latter two compounds. These studies also revealed that temelastine has relatively low affinity for mouse cortex H1-receptors compared with its affinity for H1-receptors in guinea-pig ileum and cortex, suggesting that it may be a useful compound with which to investigate potential H1-receptor tissue and species-related differences. PMID- 2881791 TI - The antinociceptive effects of prostaglandin antagonists in the rat. AB - This study examined the antinociceptive effects of two prostaglandin antagonists, SC-25469 and SC-19220 in the rat. SC-25469 and SC-19220 inhibited acetic acid induced writhing with ED50 s of 6.9 and 6.8 mg/kg p.o., respectively. When compared to other analgesics, the rank order of potency in the writhing test was morphine greater than pentazocine = U-50,488 greater than SC-25469 = SC-19220 greater than ibuprofen greater than aspirin greater than acetaminophen. SC-25469 (150 and 300 mg/kg p.o.) and SC-19220 (50-300 mg/kg p.o.) also suppressed the behavioral response to s.c. injection of formalin, as did aspirin (50-150 mg/kg p.o.), ibuprofen (25-100 mg/kg p.o.) and acetaminophen (300 mg/kg p.o.). However, the suppression was not of the magnitude observed after administration of morphine (ED50: 0.9 mg/kg s.c.), pentazocine (ED50: 2.4 mg/kg s.c.) or U-50,488 (ED50: 0.8 mg/kg s.c.). This study demonstrates the antinociceptive properties of prostaglandin antagonists in two distinct tests of nociception. PMID- 2881792 TI - Comparison of L-[3H]glutamate, D-[3H]aspartate, DL-[3H]AP5 and [3H]NMDA as ligands for NMDA receptors in crude postsynaptic densities from rat brain. AB - L-[3H]Glutamate, D-[3H]aspartate, DL-[3H]2-amino-5-phosphonovalerate (AP5) and [3H]N-methyl-D-aspartate (NMDA) were evaluated as radioligands using postsynaptic density (PSD) preparations from rat brain. L[3H]Glutamate had the highest affinity and greatest percentage specific binding, followed by D-[3H]aspartate greater than DL-[3H]AP5 greater than [3H]NMDA. The pharmacological specificity of the binding of each radioligand indicated an interaction with NMDA-preferring receptors, the order of potency of displacing compounds tested being L-glutamate greater than D-aspartate greater than D-AP5 greater than DL-AP5 greater than ibotenate greater than NMDLA greater than quisqualate. For L-[3H]glutamate, the data revealed an interaction with two sites, the major one having NMDA receptor characteristics and the minor one resembling the quisqualate-preferring receptor. Against L-[3H]glutamate binding, quisqualate showed a two-component inhibition profile with an affinity of 25 microM at the NMDA site and 0.19 microM at the quisqualate site. Thus, by using several radioligands possessing activity at NMDA receptors, we confirm that an NMDA receptor binding site is present in crude PSDs. Although it is less selective than D-[3H]aspartate, DL-[3H]AP5 and [3H]NMDA, L-[3H]glutamate remains, by virtue of its high affinity, the ligand of choice for the study of NMDA receptors in preparations where such sites predominate. PMID- 2881793 TI - Pharmacological evidence for the involvement of 1-(2-pyridinyl)-piperazine (1 PmP) in the interaction of buspirone or gepirone with noradrenergic systems. AB - We investigated in mice the effects of one of the principal metabolites of buspirone and gepirone, 1-(2-pyridinyl)-piperazine (1-PmP), on hypothermia and reduced locomotion induced by clonidine (0.25 and 0.06 mg/kg, respectively), tests related to brain alpha-adrenergic function. Both effects were antagonized dose dependently by 1-PmP (1-16 mg/kg i.p.). Moreover, pretreatment with proadifen (50 mg/kg) prevented the reversal by buspirone and gepirone of clonidine-induced hypothermia. This suggests that 1-PmP could be responsible for some of the apparent noradrenergic effects of buspirone and gepirone. PMID- 2881794 TI - Characterization of soluble bradykinin receptor-like binding sites. AB - Bradykinin (BK) receptor-like binding sites were solubilized from a particulate fraction of bovine uterine myometrium (BUM) using the zwitterionic detergent 3 [(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate (CHAPS). Scatchard analysis of [125I-Tyr1]kallidin (T1K) binding revealed a single class of soluble binding sites with KD = 0.35 nM and Bmax = 0.13 pmol/mg protein. The soluble binding sites exhibited a kinin-binding specificity comparable to that of the particulate BUM receptor-like sites. Soluble T1K binding association kinetics were first-order at the four T1K concentrations examined. A plot of the pseudo first order rate constant (Kobs) versus T1K concentration was linear, and values for the association (k1) and dissociation (k-1) rate constants were obtained. These rate constants yielded a kinetically derived equilibrium dissociation constant (KD = 0.64 nM) which was comparable to that obtained by Scatchard analysis. Biphasic dissociation of bound T1K was resolved into rapid and slow dissociation phases. The rate constant (k-1) of the rapid dissociation phase was comparable to the dissociation rate constant determined in association experiments. A biphasic loss of soluble T1K binding activity was observed with storage at 10 degrees C. PMID- 2881795 TI - Inotropic effects of calcitonin gene-related peptide, vasoactive intestinal polypeptide and somatostatin on the human right atrium in vitro. AB - Inotropic responses to calcitonin gene-related peptide (alpha-CGRP), substance P, neurokinin A, capsaicin, neuropeptide Y, vasoactive intestinal polypeptide (VIP) and somatostatin (Som, 14 and 28 were analysed using the isolated, electrically driven auricle of the human right atrium. alpha-CGRP and VIP stimulated atrial contractility concentration dependently. alpha-CGRP was about 10-fold more potent than noradrenaline (NA) as an inotropic agent. Phentolamine plus metoprolol decreased the atrial response to NA significantly while the alpha-CGRP effect remained unchanged. Som did not influence the basal contractility of the atria, which, however, was inhibited by acetylcholine (ACh). ACh, Som 14 and Som 28 inhibited the NA-induced stimulation of atrial contractility, whereby Som 28 was more potent than Som 14. The inhibitory effects of ACh were completely blocked by atropine which did not influence the response to Som. Capsaicin, substance P, neurokinin A, neuropeptide Y (NPY) and the NPY fragments 1-19 and 26-36 did not induce any changes in contractility of the electrically driven human atrium. The present results suggest that some of the recently discovered neuropeptides (alpha CGRP, VIP and Som) could be of importance in the regulation of cardiac contractility in man. PMID- 2881796 TI - Neurotransmitter levels in the hypothalamus during postnatal development of rats. AB - The content of norepinephrine (NE), epinephrine (E), dopamine (DA) and serotonin (5-HT) in the rat hypothalamus was determined at four hours time interval during 24 hours period at the age of 12, 23, 27 and 75 days. It was found that the content of NE in the hypothalamus is low in 12 day-old rats, and during the postnatal period a gradual increase of NE was noted. The content of E in the hypothalamus is low in 12- to 27-day-old rats and an important increase was found in adult animals. The high values of DA and 5-HT concentration were found in the hypothalamus of 12-day-old rats and a transient decrease of 5-HT and DA at the age of 23 days was noted, further an important increase of the content of both neurotransmitters in the hypothalamus was demonstrated later in life. The presence of circadian rhythm of hypothalamic NE, E, DA and 5-HT content was found in 12-, 23-, 27-day-old and in adult rats overfed or underfed during the suckling period. However, no significant correlation was observed between the NE and E levels in the hypothalamus and the diurnal fluctuations of plasma corticosterone concentrations. In adult animals an inverse correlation between the plasma corticosterone level and hypothalamic 5-HT content was noted. In young 12- and 23 day-old rats the correlation between 5-HT in the hypothalamus and corticosterone in the plasma was positive. These results indicate that the shift of peak in plasma corticosterone levels during postnatal ontogenesis of rats observed in previous experiments is not dependent on the changes in diurnal fluctuation of hypothalamic neurotransmitter concentrations. PMID- 2881797 TI - Occurrence of calcitonin, somatostatin-like immunoreactivity, and carcinoembryonic antigen in two sisters suffering from familial thyroid medullary carcinoma. AB - The presence of calcitonin, somatostatin-like immunoreactivity and carcinoembryonic antigen in tumor tissues (surgically obtained) and identified by the peroxidase-antiperoxidase technique, is reported in two sisters suffering from familial thyroid medullary carcinoma. C-cell hyperplasia occurred in both individuals. Preoperatively, both patients had elevated calcitonin serum levels (290 pM, 991.8 ng/l), and carcinoembryonic antigen (60 micrograms/l). No ACTH or thyroglobulin immunoreactivity could be found in the tumor tissue. After thyroidectomy, 131I-treatment and percutaneous radiation, somatostatin-like immunoreactivity and carcinoembryonic antigen plasma levels were in the normal range, whereas calcitonin was still elevated. It is proposed that calcitonin, somatostatin, and carcinoembryonic antigen are produced by the thyroid medullary carcinoma. PMID- 2881798 TI - Possible windborne spread of myxomatosis to England in 1953. AB - An analysis of the meterological conditions showed that the first outbreaks of myxomatosis in S.E. England in 1953 could have resulted from wind carriage of insects infected with myxoma virus from northern France. South-easterly winds on the night 11-12 August would have carried the insects 120-160 km from the Departements of Nord, Pas de Calais and Somme across the English Channel to near Edenbridge, Kent. The flight would have taken 6.5-8.5 h at wind speeds of 15-22 km h-1. On the night 11-12 August, temperatures increased with height (inversion) up to 500 m; at ground level temperature was around 19 degrees C and at 500 m was 25 degrees C. Insects would have travelled up to the top of the inversion arriving on 12 August as the inversion declined. Two or possibly three generations of infection would have taken place before the disease was seen around the middle of September 1953. The most likely insect was the mosquito Anopheles atroparvus which breeds along the coastal marshes of England and northern France and which has been shown experimentally and in the field to transmit myxoma virus mechanically. PMID- 2881799 TI - The effect of levobunolol on aqueous humor dynamics. AB - We evaluated the acute effects of installation of 0.5% levobunolol on aqueous humor dynamics in a double-masked study in 18 patients with ocular hypertension. Aqueous flow was measured by fluorophotometry and total outflow facility by tonography. Aqueous flow decreased approximately 29% in the eyes treated with levobunolol. Total outflow facility and episcleral venous pressure measurements were similar in levobunolol-treated eyes and contralateral eyes treated with vehicle. A 36% decrease in intraocular pressure was observed in the levobunolol treated eyes and a slight intraocular pressure reduction was seen in the vehicle treated eyes. The results of this study indicate that, similar to timolol, levobunolol lowers intraocular pressure primarily by decreasing aqueous humour production. PMID- 2881800 TI - Initial nociceptive sensitization in carrageenin-induced rat paw inflammation is dependent on amine autacoid mechanisms: electrophysiological and behavioural evidence obtained with a quaternary antihistamine, thiazinamium. AB - We have studied the ability of a quaternary antihistamine, thiazinamium, to inhibit the nociceptive sensitization that occurs early, during the first hour, following intraplantar injection of the polysaccharide carrageenin in the rat. Parallel studies were performed with an electrophysiological model (changes in responsiveness of ventro-basal thalamic cells driven by noxious stimulation of the paws), and a behavioural test (changes in threshold stimulus necessary to elicit vocalization by gradually increased pressure to the paws). When thiazinamium was given intravenously 10 min before carrageenin, no sensitization due to inflammation was found in either test. By contrast, when thiazinamium was administered 20 min after carrageenin, there was a clear sensitization in both tests that did not differ from that found in animals not treated with the antagonist. Paw oedema was also slightly decreased by pretreatment with thiazinamium. These results suggests that early inflammatory sensitization of peripheral nociceptors is mainly dependent on an initial release of histamine (and/or serotonin, since thiazinamium could also have some antiserotoninergic activity). PMID- 2881801 TI - Brain tissue transplantation in neonatal rats prevents a lesion-induced syndrome of adipsia, aphagia and akinesia. AB - Previous experiments have proven brain tissue transplantation effective in reversing lesion-induced behavioral deficits in mature rats. This study reversed the usual experimental paradigm, so that fetal substantia nigra was transplanted into intact neonatal rats and allowed to mature in the host brain. Upon maturation substantia nigra lesions were made bilaterally to reveal the functional contribution of the transplanted tissue. In control animals these lesions depleted striatal dopamine, producing rigidity, poverty of movement and abnormal posture comparable to Parkinson's disease in the human; cessation of feeding and drinking led to progressive weight loss and death. In contrast, fetal substantia nigra transplanted into the neonatal rat became well-integrated in the host brain and was shown to protect the animal from this syndrome produced by subsequent substantia nigra lesions. We suggest that transplantation in these neonatal rats was performed during a crucial period of synaptogenesis, an environment particularly favorable to host-transplant interaction. PMID- 2881803 TI - Glutamate-like immunoreactive structures in primary sensory neurons in the rat detected by a specific antiserum against glutamate. AB - We found that large cells in the dorsal root and trigeminal ganglia contained glutamate-like immunoreactivity. Immunoreactive neurons were not detected in the superior cervical or pterygopalatine ganglia. These findings indicated that glutamate is a neurotransmitter or neuromodulator of large cells of sensory ganglia. PMID- 2881802 TI - Reduced excitatory effect of kainic acid on rat CA3 hippocampal pyramidal neurons following destruction of the mossy projection with colchicine. AB - Rats were injected unilaterally with colchicine in the dentate gyrus of the dorsal hippocampus. Two weeks later, under urethane anesthesia, extracellular recordings were obtained on both sides from pyramidal neurons of the CA1 and of the CA3 regions of the dorsal hippocampus. Microiontophoresis was used to assess the responsiveness of these neurons to kainate, glutamate and ibotenate. The colchicine injection produced a nearly complete destruction of the granule cells of the ipsilateral dentate gyrus and of their mossy fiber projections to CA3 without apparently affecting other hippocampal neurons. On the lesioned side, the potency of kainate in activating CA3 pyramidal neurons was reduced by 94% compared to the same neurons on the intact side. However, the excitatory effect of glutamate was unchanged and that of ibotenate only slightly reduced. Kainate was 80 times more potent in activating CA3 than CA1 pyramidal neurons on the intact side, whereas this ratio had dropped to 2.6 on the lesioned side. The selective decrease of the effectiveness of kainate in activating CA3 pyramidal neurons following the colchicine lesion suggests that this amino acid, but not glutamate and ibotenate, produces most of its excitatory effect in the intact CA3 region by releasing (an) excitatory neurotransmitter(s) from mossy fibers terminals, the nature of which remains to be identified. PMID- 2881804 TI - Recording of mouse ventral tegmental area dopamine-containing neurons. AB - We examined the electrophysiologic and pharmacologic properties of dopamine containing ventral tegmental area neurons in the mouse using extracellular single unit recording techniques in both chloral hydrate-anesthetized mice and in vitro mouse midbrain slices. In vivo the ventral tegmental area neurons had long duration action potentials (2 to 5 ms) and discharged at 1 to 9 spikes/s with either a decremental burst pattern or a regular pattern. Systemic administration of the dopamine agonist, apomorphine, decreased their firing rate, and the dopamine receptor blocker, haloperidol, reversed this effect. Similarly, systemic administration of the dopamine-releasing agent, d-amphetamine, suppressed their discharge rate, an effect blocked by pretreatment of the animals with alpha methyl-p-tyrosine. When recorded in vitro from midbrain slices, ventral tegmental area neurons showed electrophysiologic properties similar to those found in vivo; however, the neurons recorded in vitro fired at a significantly faster rate and their firing pattern tended to be more pacemaker-like, especially when recordings were made in an incubation medium that blocked synaptic transmission (i.e., low calcium/high magnesium). The activity of most of these neurons was suppressed by addition of apomorphine to the incubation medium, an effect reversed by haloperidol. Pretreatment with alpha-methyl-p-tyrosine produced no significant change in the discharge pattern or rate for cells recorded in vitro. These data indicate that mouse ventral tegmental area dopamine neurons in vivo exhibit the same electrophysiologic and pharmacologic properties as do rat and cat dopamine containing neurons and that in vitro they fire with pacemaker regularity in a low calcium/high-magnesium medium. The in vitro preparation offers an approach to examining the fundamental properties of ventral tegmental area dopamine containing neurons in the absence of afferent inputs. PMID- 2881805 TI - Effect of cysteamine on cytosolic somatostatin binding sites in rabbit duodenal mucosa. AB - Administration of cysteamine in rabbits elicited a rapid depletion of both duodenal mucosa and plasma somatostatin. A significant reduction was observed within 5 min, returning toward control values by 150 min. The depletion of somatostatin was associated with an increase in the binding capacity and a decrease in the affinity of both high- and low-affinity binding sites present in cytosol of duodenal mucosa. Incubation of cytosolic fraction from control rabbits with 1 mM cysteamine did not modify somatostatin binding. Furthermore, addition of cysteamine at the time of binding assay did not affect the integrity of 125I Tyr11-somatostatin. It is concluded that in vivo administration of cysteamine to rabbits depletes both duodenal mucosa and plasma somatostatin and leads to up regulation of duodenal somatostatin binding sites. PMID- 2881806 TI - A quantitative analysis of the metabolic pathways of hepatic glucose synthesis in vivo with 13C-labeled substrates. AB - A quantitative analysis of the major metabolic pathways of hepatic glucose synthesis in fasted rats was conducted. [2-13C]Acetate was administered intraintestinally into awake fasted rats. 13C NMR and GC-MS analysis were used to quantitate the isotopic enrichments of glutamate, glutamine, lactate, alanine and the newly synthesized liver glucose. By measuring the ratio of carbon atoms in glutamate molecules derived from acetyl-CoA to carbon atoms in the glucose molecule derived from oxaloacetate and gluconeogenic substrates, such as lactate and alanine, the relative activities of the Krebs cycle and gluconeogenesis were quantified. Our results indicate that the percentage of glucose carbons originating by 'metabolic exchange' with the oxaloacetate pool, via the Krebs cycle, is less than 7%. PMID- 2881807 TI - Amino acid neurotransmitters in the CNS. Relationships between net uptake and exchange in rat brain synaptosomes. AB - Carefully isolated, metabolically competent rat brain synaptosomes accumulate acidic amino acid neurotransmitters down to very low external levels. This supports the suggestion that nerve endings are involved in terminating transmission at the synapses and in maintaining low levels of these molecules in the external environment in the brain. At saturating levels of acidic amino acids, the rate of inward and outward movements of the Na+-amino acid complex (exchange) is much faster than the net uptake. The transmembrane gradients of aspartate and glutamate approach each other under all conditions explored which indicates that these two amino acids share the same transport system. PMID- 2881808 TI - Regulatory role of the ATPase inhibitor protein on proton conduction by mitochondrial H+-ATPase complex. AB - This study shows that the natural inhibitor protein of mitochondrial H+-ATPase complex (IF1) inhibits, in addition to the catalytic activity, the proton conductivity of the complex. The inhibition of ATPase activity by IF1 is less effective in the purified F1 than in submitochondrial particles where F1 is bound to F0. No inhibition of H+ conductivity by F0 is observed in F1-depleted particles. PMID- 2881809 TI - Effects of organic solvents and orthophosphate on the ATPase activity of F1 ATPase. AB - The ATPase activity of soluble F1 ATPase of mitochondria is activated by Pi. The concentration of Pi required for half-maximal activation decreases from a value higher than 50 mM to about 1 mM Pi when one of the organic solvents dimethyl sulfoxide (15 to 30%), methanol (7.5 to 15%) or ethylene glycol (10 to 30%) is added to the assay medium. This effect is observed in the presence of MgCl2 but not in the presence of CaCl2. PMID- 2881810 TI - Mode of inhibition of sodium azide on H+-ATPase of Escherichia coli. AB - Sodium azide inhibited multi-site (steady-state) ATPase activity of E. coli F1 more than 90%, but did not affect uni-site (single-site) ATPase activity. Thus azide inhibited multi-site ATPase activity by lowering catalytic cooperativity. Consistent with this observation, azide changed the ligand-induced fluorescence response of aurovertin bound to F1. PMID- 2881811 TI - The molecular basis of the inherited deficiency of androsterone UDP glucuronyltransferase in Wistar rats. AB - A major UDP-glucuronyltransferase isoenzyme in rat liver (51 kDa), corresponding to androsterone glucuronidating activity, has been identified by immunoblot analysis. This isoenzyme is absent from Wistar rats exhibiting the low androsterone (LA) UDP-glucuronyltransferase activity exhibiting the low androsterone (LA) UDP-glucuronyltransferase activity phenotype. Northern blot analysis of total RNA from normal and androsterone glucuronidation deficient Wistar rats demonstrated that the mRNA encoding this protein was not synthesised. Differences in restriction fragment length observed on Southern blotting of genomic DNA from LA Wistar rats indicate that this inherited deficiency is the result of a deletion in the androsterone UDP-glucuronyltransferase gene. PMID- 2881813 TI - Ontogeny of luteinizing hormone releasing hormone (LHRH) and somatostatin (SRIF) in the hypothalamus of the sheep. AB - Using the immunoperoxidase method, luteinizing hormone releasing hormone (LHRH) and somatostatin (SRIF) were demonstrated in the hypothalamus of fetal sheep. Both hormones were found in the perikarya at about day 60 of fetal life, i.e., at the end of the first half of pregnancy. Immunoreactive LHRH (irLHRH) perikarya were situated in the vicinity of the organum vasculosum of the lamina terminalis (OVLT), i.e., in the medial preoptic nucleus and in the nucleus of the diagonal band of Broca. They were scattered and generally sparse in these areas. In the earliest stages of fetal life (60, 75, 90 days of gestation) irSRIF perikarya grouped in the ventromedial nucleus and in the lateral preoptic nucleus, were very numerous. In the oldest fetuses (120 and 135 days of gestation) they had disappeared from these nuclei but could be found in some extrahypothalamic regions--the amygdala, septo-olfactory area and sometimes in the anterior periventricular zone of the hypothalamus. Neither irLHRH nor irSRIF material were stored in the nerve terminals of the external layer of the median eminence (ME) before day 75 of gestation. In all developmental stages examined, irLHRH material in the ME was very scarce whereas irSRIF material very aboundant. PMID- 2881812 TI - When to operate on open angle glaucoma. AB - The aim of treatment in primary angle glaucoma should be to reduce the intraocular pressure throughout the 24 hours to a level where no damage is done to the optic nerve head, thus preventing any field defect. Open angle glaucoma as it is presently defined requires a significantly raised intraocular pressure to be associated with detectable changes in the optic nerve and a consequent visual field defect. The goal is therefore unattainable whilst this definition remains. The best that can be achieved is to reduce the intraocular pressure to such a level that no further disc damage occurs. Unfortunately, because there is no method of measuring the intraocular pressure over 24 hours, large diurnal rises of pressure may well remain undetected, producing irreparable damage to the disc. Furthermore, significant nerve fibre loss occurs before any field defect is detected even by the most sophisticated testing techniques and some patients develop field defects in spite of normal intraocular pressures. Treatment therefore is largely empirical, relying on the coarse assessment of visual fields, intermittent measurements of intraocular pressure and the clinical observation of the optic nerve head. Chronic open angle glaucoma is a disastrous, insidious disease destructive to the optic nerve head. It is difficult to diagnose before serious damage has occurred and it is difficult to monitor once it has been discovered. Medical therapy was successful in preventing field loss in one third of patients when the medication was given infrequently and in low dosage. Higher dosages were poorly tolerated and the drugs were often not taken by the patient. No advantage was obtained by increasing the strength and frequency of the medication because any improvement was transient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881814 TI - Fixed eruption to sulphasalazine. PMID- 2881815 TI - A molecular genetic approach to the study of catecholamines. PMID- 2881816 TI - Molecular mechanism of ATP synthesis in oxidative phosphorylation. AB - The experiments described in this paper may perhaps point the way towards a reaction mechanism for oxidative phosphorylation. However, we are not yet in a position to write a detailed chemical equation, supported by experimental evidence, for the mechanism of ATP synthesis. Continued pursuit of some of the implications of these experiments will be very much dependent on information presently unavailable. For example, it would be of great value to have three dimensional X-ray crystal structures for F0 as well as F1. It will also be important to know the pathway of proton translocation through the ATPase complex. We shall surely require entirely new experimental tools to probe many of these questions. PMID- 2881817 TI - Distribution and activation of protein kinase C in the rat testis tissue. AB - The distribution and role of the calcium-activated, phospholipid-dependent protein kinase C (PK-C) was studied in rat testis. When testis tissue was homogenized in the presence of 2 mmol/l EDTA and EGTA, the majority (greater than 70%) of the PK-C activity was soluble, the rest was released from the particulate fraction by solubilization with 0.3% Triton X-100. Without chelating agents the soluble PK-C activity was undetectable, and only partially recovered from solubilized membranes. Preincubation of the tissue with the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA, 10(-7) mol/l) translocated PK-C to the membranes, and the majority of this activity was recovered by solubilization. Mobility of testicular soluble PK-C activity in HPLC DEAE cellulose chromatography was similar to that of the brain enzyme. This single step purified testicular PK-C activity 140-fold. The specific activity and subcellular distribution of PK-C was similar in whole testis tissue and separated seminiferous tubules (160-210 pmol 32P X mg protein-1 X min-1 in the soluble and particulate fractions), but 2- to 3-fold higher in purified Leydig cells. However, the majority of total testicular PK-C activity appeared to be of tubular origin. Unilateral cryptorchidism for 1 week reduced PK-C of the abdominal testis by 50%, and the activity of dissected seminiferous tubules varied according to the epithelial wave. Both findings suggest that the bulk of the activity resides in the seminiferous epithelium. Involvement of PK-C in Leydig cell function was demonstrated using the TPA, which at 10(-7) mol/l inhibited basal cAMP production by 50% (P less than 0.01) but increased that of testosterone by 2- to 3-fold (P less than 0.01). On the other hand, when incubated with hCG, TPA inhibited both cAMP and testosterone production; the ED50s of hCG stimulation increased 4- to 10 fold with both parameters. It is concluded that PK-C activity is present in both the seminiferous tubules and Leydig cells, and is involved in the regulation of these testicular compartments. Its total activity and subcellular distribution are at variance according to the functional state and endocrine milieu of the testis. PMID- 2881818 TI - Differentiation of prospective mouse pancreatic islet cells during development in vitro and during regeneration. AB - The pancreatic islets of mouse embryos are comprised of four different endocrine cell types and of cells containing a hormone (i.e., glucagon) and a catecholamine enzyme (tyrosine hydroxylase, TH) which appear sequentially during development in vivo. The presence of TH in glucagon cells, however, is transient, since adult pancreatic A cells do not express the enzyme. In this study we sought to determine whether the endocrine precursor cells are primed to differentiate and express catecholamine enzymes during their maturation following a predetermined sequence or whether these processes are regulated by environmental cues. To answer this question, we used immunocytochemical procedures to examine the differentiation of pancreatic rudiments removed from E11 mouse embryos and maintained in culture and of pancreases that regenerated in vitro from E11 pancreatic ducts. We found that although all the endocrine cell types differentiate in the gland in culture, the sequence of their appearance is different from that in vivo, suggesting that the timing of differentiation may be regulated by environmental factors. We also found that, in vitro, the pancreas contains TH-glucagon cells, indicating that the expression of the enzyme by pancreatic A cells is independent of factors present in vivo. Moreover, the fact that the TH-glucagon cells also differentiate during pancreatic regeneration suggests that the expression of the enzyme may be a characteristic stage of endocrine cell precursors during maturation. PMID- 2881819 TI - Lack of adjuvant effect of the pertussis component on IPV DTP-polio vaccine in children. AB - On day 0, four groups of children (3 to 6 months old) randomly received IPV alone or IPV + pertussis, or IPV + DP, or IPV + DTP. At days 28 and 56, all the children received the same IPV + DTP vaccine. Polio neutralizing and diphtheria antibodies were determined at days 0, 28 and 56. No adjuvant and even some inhibitory effect of pertussis was observed at days 28 and 56 on mean polio antibody titers. These results are compared to those observed with diphtheria. PMID- 2881820 TI - Use of a combined DTP-polio vaccine in a reduced schedule. AB - A five-year serologic follow-up and a four-year monitoring of the polio and pertussis morbidity in an area immunized with a 2 + 1 dose schedule of a combined DTP-Po vaccine have shown that: the individual protection against polio measured by the presence of neutralizing antibody persists at a very adequate level five years after the first booster; after three years of a steady high proportion of children with pertussis antibody, a considerable drop is observed and in about 28% of individuals agglutinin levels of less than 1:20 were found five years after booster; the community protection against paralytic poliomyelitis and pertussis is satisfactory up to four years after the introduction of the program. Continuation of immunization with a 2 + 1 dose schedule at a maximal coverage and close seroepidemiologic surveillance are necessary in order to draw definite conclusions, because of the potentially strong impact of very dynamic ecological factors present in our geopolitical area upon the agent-host interrelationship. PMID- 2881822 TI - Comparative study of rat-paw oedema tests for assessing reactivity of B. pertussis-containing combined vaccines. AB - Two volumetric (electrocapacity plethysmography and mercury volumetry) and two linear methods (a new type of scale and a calliper rule) for rat-paw oedema measurement used in local reactivity of combined vaccines containing a B. pertussis component were compared. The reproducibility and sensitivity of the methods was tested on a diphtheria-tetanus-pertussis vaccine and a toxic pertussis suspension. The linear methods proved more adequate for measuring small and chiefly unidirectionally (vertically) progressing oedemas. PMID- 2881821 TI - Simultaneous administration of diphtheria/tetanus/pertussis/polio vaccine and hepatitis B vaccine in a simplified immunization programme. AB - In most developing countries hepatitis B virus is endemic and prevention has to be carried out early in life and on a mass scale. In these regions, simultaneous administration of multiple antigens is normal practice. We have therefore, investigated the interaction of hepatitis B vaccine with DTP-Polio vaccine. Studies include the immune response post one and two injections to diphtheria and tetanus toxoid, pertussis and hepatitis B surface antigen. The vaccines were given simultaneously or not at a 6 months interval. The immune response to HBsAg vaccine and DTP-Polio vaccine injected simultaneously was equal to the immune response observed after administration of vaccines alone. Moreover, no adverse reactions were noted. This trial also demonstrated that immunization with two doses of DTP-Polio vaccine, containing 30 Lf of diphtheria and tetanus toxoids, at a 6 months interval is sufficient to obtain a very good immune response. PMID- 2881823 TI - Antral gastrin and somatostatin cell populations in rats after chronic administration of histamine. AB - Variations in the size of the antral G and D cell populations under the effect of chronic stimulation of acid secretion with histamine were investigated in male Wistar rats. Osmotic minipumps delivering either 0.9% saline or histamine dihydrochloride (4.5 mg/kg/h) were implanted subcutaneously in gastric-fistula rats. Gastric secretion was collected prior to the implantation of the pump, after 7 days and after 14 days. Total antral G and D cell numbers and the G/D ratio were estimated at the end of the experiment. Administration of histamine during 14 days did not induce significant changes in the number of either G or D cells in the antrum despite a 3-fold increase in acid secretion. PMID- 2881824 TI - Autonomic nervous control of fundic secretion of somatostatin and antral secretion of gastrin and somatostatin in pigs. AB - By selective catheterization of gastric veins, we studied the secretion of gastrin and somatostatin from the antrum and of somatostatin from the gastric fundus-corpus region in anaesthetized pigs with or without acute adrenalectomy. The secretion was studied during electrical stimulation of the vagus nerves and the splanchnic nerves and simultaneous irrigation of gastric lumen with fluids of high, low, and neutral pH. The corpus-fundus somatostatin response to vagal stimulation was biphasic with a short-lasting initial increase followed by a lasting inhibition, which was little influenced by intraluminal pH or adrenalectomy. In pigs with intact adrenals, antral somatostatin secretion was increased by vagal stimulation, whereas in adrenalectomized pigs, the effect was inhibitory. The vagally induced inhibition was abolished when the intragastric pH was kept at pH 2. The antral gastrin secretion was strongly stimulated by vagal stimulation. The magnitude of the secretory response was inversely related to the pre-stimulatory somatostatin levels, but not to the nerve stimulation responses. Splanchnic stimulation increased arterial blood pressure and gastric blood flow, but had inconsistent effects on somatostatin and gastrin secretion. PMID- 2881826 TI - Alterations in serum gastrin levels and antral G- and D-cell population following corticosteroid administration. RIA and immunocytochemical long-term study in guinea pigs. AB - Fourteen guinea pigs were given prednisolone daily for 20 days and 11 for 40 days. Another 20 formed the two control groups. Short-term prednisolone treatment significantly increased serum gastrin levels and antral G-cell population as compared to the control group. The same parameters significantly decreased following 40 days of prednisolone treatment as compared to the group of short term prednisolone treatment. Forty days of prednisolone treatment significantly increased antral D-cell population as compared to the control and short-term prednisolone treatment groups. It is concluded that hypergastrinaemia and antral G-cell hyperplasia following corticosteroid administration is temporary and is accompanied by antral D-cell hyperplasia. PMID- 2881825 TI - Somatostatin effect on rectal muscle in human healthy volunteers. AB - The effect of somatostatin on the rectal muscle has been studied in 15 healthy volunteers who received on 2 separate days and in a random order a continuous 1 hour infusion somatostatin (250 micrograms initially as an intravenous bolus and then 250 micrograms/h via infusion) or placebo (saline 0.15 M). Our results show that somatostatin significantly reduces the rectal basal tone after 30 and 50 min of infusion without modifying the rectal distensibility. Although they were obtained through a pharmacological increase of plasma somatostatin levels, these data suggest that somatostatin could play a part in the reservoir function of the rectum. PMID- 2881827 TI - [New frontiers in human genetics and their implications]. PMID- 2881828 TI - [Non-steroidal anti-inflammatory agents and their effects on mitochondrial function]. PMID- 2881829 TI - [Beta-blockers and digestive hemorrhages]. PMID- 2881830 TI - Effects of somatostatin on gallbladder emptying. AB - Because approximately 80% of reported patients with somatostatinomas have gallstones, this study was performed to determine the effects of exogenous somatostatin on gallbladder emptying responses to liquid and solid meals, direct cholinergic stimulation by bethanechol, indirect cholinergic stimulation by sham feeding, and intravenously administered octapeptide of cholecystokinin. Gallbladder emptying was quantitated using 99mTc-HIDA and a gamma-camera on line to a digital computer. Somatostatin, administered at a dosage of 7 micrograms/kg X h, prevented the gallbladder emptying responses to both test meals, sham feeding, and bethanechol. The maximal gallbladder emptying response to octapeptide of cholecystokinin at 5.0 ng/kg X min was reduced from 93.2% +/- 4.8% to 57.1% +/- 9.9% (p less than 0.01) and to octapeptide of cholecystokinin at 0.5 ng/kg X min from 91.3% +/- 5.3% to 14.8% +/- 4.2% (p less than 0.01). These findings suggest that somatostatin is a potent inhibitor of gallbladder emptying in humans. This may be an important factor in the development of gallstones in patients with somatostatinomas. PMID- 2881831 TI - Effects of monoclonal antibodies to somatostatin on somatostatin-induced and intestinal fat-induced inhibition of gastric acid secretion in the rat. AB - Cell lines producing monoclonal antibodies to somatostatin, designated S10 and S20, have recently been generated. The purpose of the present immunoneutralization study was to examine the ability of these antibodies to block the inhibitory effect of exogenous somatostatin on meal-stimulated gastric acid secretion in the innervated rat stomach and to use these antibodies as probes to determine if somatostatin is involved in intestinal fat-induced inhibition of gastric acid secretion. The plateau acid secretory response to a liver extract meal in this model was 28 +/- 2 mu Eq/30 min. Intravenous infusion of somatostatin at 2.0 micrograms/kg X h or intraduodenal oleic acid at 1.2 ml/h reduced this response to 12 +/- 1 and 14 +/- 1 mu Eq/30 min, respectively. The antibodies were given intravenously 1 h before the meal and either somatostatin or intraduodenal oleic acid infusion. S10 preinfusion returned the plateau meal responses to the levels seen with the meal alone: 25 +/- 4 and 26 +/- 1 mu Eq/30 min, respectively. S20 preinfusion had no effect, the responses being 14 +/- 1 and 16 +/- 1 mu Eq/30 min, respectively. These results demonstrate successful binding of exogenous somatostatin by S10 in vivo and reversal of intestinal fat induced inhibition of gastric acid secretion by S10 preinfusion. It is concluded that the mechanism whereby fat in the small intestine inhibits gastric acid secretion may involve the release of somatostatin. PMID- 2881832 TI - Reduction of food intake by fencamfamine in rats. AB - Fencamfamine (1.0-10.0 mg/kg, i.p. single dose) reduced the food intake in a dose effect relationship. The dose needed for the 50% inhibition of food intake (ID50) was 7.3 mg/kg. Fencamfamine-induced anorexia in rats (5.0 and 10.0 mg/kg) was followed by hyperactivity, stereotypy or both. Pretreatment with haloperidol antagonized the anoretic effect induced by fencamfamine. These findings suggest that the activation of central dopaminergic systems involved in feeding regulation may be responsible for the anoretic effect of fencamfamine and that this effect is associated with other central stimulant effects. PMID- 2881833 TI - Partial agonists at guinea-pig atrial beta-adrenoceptors display relaxation responses in the guinea-pig ileum independent of beta-adrenoceptor stimulation. AB - The beta-adrenoceptor mediated responses of oxyfedrine, ritodrine, tazolol, prenalterol, salbutamol and carteolol were examined on guinea-pig left and right atrial and ileal preparations. All agonists tested in left and right atrial preparations were partial agonists relative to isoprenaline. All agonists with the exception of salbutamol, which appeared a full agonist, produced relaxation responses significantly greater than isoprenaline in ileal preparations. The response to ritodrine in the ileum was not influenced by practolol, in a concentration which antagonized the responses of ritodrine in the right atria. The response of the ileum to beta-adrenoceptor antagonists of varying lipophyllicity was examined. Propranolol and pindolol both produced relaxation responses relative to their lipophyllicities. No relaxation was observed to atenolol, which exhibits very low lipophyllicity. It is concluded that beta adrenoceptor agonists exhibit a substantial relaxation of guinea-pig ileum that is independent of beta-adrenoceptor stimulation. PMID- 2881834 TI - Influence of oxypangam upon the induction of tyrosine aminotransferase, the NAD content and the ADPR transferase activity in several organs of the rat. AB - Oxypangam is a substance applied therapeutically against a number of diseases, such as chronic liver damages, angina pectoris, and psychosomatic disturbances. The mode of action of oxypangam has not yet conclusively been described. The only well-known properties of this substance are its intensive methylating and lipolytic effects. The present paper serves to elucidate the influence of oxypangam on the induction of the tyrosine aminotransferase, on the NAD content and on the activity of the ADPR transferase in the liver. Our studies showed that in normal animals, increasing doses of oxypangam support the induction of tyrosine aminotransferase. Up to a concentration of 100 mg/kg oxypangam enhances also the induction of tyrosine aminotransferase by tryptophan. In both cases, however, it does not work in adrenalectomized animals. Under the influence of oxypangam the NAD content of the liver remained unchanged, while the activity of the ADPR transferase was influenced only slightly. PMID- 2881835 TI - Involvement of noradrenergic systems in the effects of conditioning stimulation of the lower brain stem on the lumbar spinal reflex in rats. AB - The effects of conditioning stimulation at various positions in the pons and the medulla on the lumbar spinal monosynaptic reflex (MSR) were examined in rats. The conditioning stimulation facilitated the MSR. Facilitation with long latency was completely blocked by phenoxybenzamine, chlorpromazine or haloperidol. Phenoxybenzamine and chlorpromazine inhibited the MSR. Haloperidol, on the other hand, augmented the MSR, and this effect became more potent after the brain stem had been transected at the upper part of the medulla oblongata. These results suggest that pontine noradreneric systems have a facilitatory influence on the MSR via alpha-adrenoceptors, and that alpha-blockers exert an inhibitory effect on the MSR by blocking these receptors. PMID- 2881836 TI - Neurotransmitters in "the smoke reflex" in rabbits. AB - An acute form of "stress-analgesia" is evoked by allowing the smoke of a cigarette to envelope the nostrils of unanaesthetized rabbits. The response consists of an immediate and generalized arrest of spontaneous movements, including respiration and expiration, reduced muscular tone, and unresponsiveness to pinching. This motor "paralysis" is accompanied by a profound bradycardia. Attempts have been made to identify the neurotransmitters involved in "the smoke reflex" by the intervention of antagonists and psychopharmaca. The bradycardia was selectively blocked by atropine, leaving the somatomotor inhibition unaltered. All components of the response were abolished by approximately 60% by clonidine and by 40% by the tricyclic antidepressant amitriptyline, both of which are known to attenuate the release of noradrenaline as agonsits of alpha 2 adrenoceptors. Yohimbine blocked the clonidine effect. Naloxone (1-2 mg/kg), p chlorphenylalanine and dexamethasone failed to influence the reflex response, suggesting that opiate, serotonergic and ACTH-systems do not play a critical role. The same applied to the benzodiazepine chlordiapoxide. The results suggest that this acute stress-induced analgesia is mediated via a noradrenergic system. The relationship of the smoke reflex to "the fear paralysis reflex", a possible trigger mechanism for the sudden infant death syndrome, is discussed. PMID- 2881837 TI - (+/-)-1-[[2-(3,4-Dimethoxphenyl)ethyl]amino]-3-(3-methylphenoxy)-2- propanol hydrochloride (bevantolol, NC-1400) as a beta 1-selective adrenoceptor blocker with alpha 1-adrenoceptor blocking activity. AB - Blocking activities of alpha- and beta-adrenoceptors by (+/-)-1-[[2-(3,4 dimethoxyphenyl)-ethyl]amino]-3-(3-methylphenoxy)-2 -propanol hydrochloride (NC 1400) were tested on the isolated muscles, comparing with those of labetalol and atenolol. In blocking the beta 1-adrenoceptor, NC-1400 was slightly more potent than labetalol and atenolol. NC-1400 was about 1/10th as potent as labetalol and about ten times as potent as atenolol in blocking the beta 2-receptor. NC-1400 was beta 1-adrenoceptor selective. NC-1400 was about 1/30th as potent as labetalol in blocking the alpha 1-receptor. NC-1400 did not interact with the alpha 2-adrenoceptor in concentrations up to 10(-5) M. The present results indicate that NC-1400 is the selective beta 1-adrenoceptor blocker with some blocking activity of alpha 1-adrenoceptors. PMID- 2881838 TI - Immunolocalization of insulin, glucagon, pancreatic polypeptide, and somatostatin in the pancreatic islets of the possum, Trichosurus vulpecula. AB - Antibodies to insulin, glucagon, pancreatic polypeptide (PP), and somatostatin were used in the immunofluorescence procedure to demonstrate localization of the four hormones in cells of the pancreatic islets of the brushtailed possum, Trichosurus vulpecula. Most pancreatic islets revealed some differences in the topographical distribution and cell number of each endocrine cell type. Insulin immunoreactive cells were observed in most islets where they occurred as groups of cells peripherally and within the islet. In several islets glucagon cells were the predominant cell population and were distributed peripherally as well as centrally. Pancreatic polypeptide cells were fewer in number and usually occurred as single cells within the islet. Cells immunoreactive to antisomatostatin serum were observed in varying numbers in the peripheral and central regions of the islet. The present immunofluorescence study demonstrates differences in the topographical distribution of the four major pancreatic hormones between a marsupial species and several of the eutherian mammals. PMID- 2881839 TI - Somatostatin-like peptide and regeneration capacities in planarians. AB - The presence of a neuropeptide immunologically related to somatostatin (SRIF) has been investigated in the neurosecretory cells of two regenerating planarian species (Dugesia lugubris and Dendrocoelum lacteum). A correlation has been shown between the discharge of the SRIF-like-immunoreactive cells during the first hours after amputation and the capacity to regenerate, and between the persistence of numerous positive cells and the lack of regeneration. These results suggest that somatostatin might play a regulatory (inhibitory) role on the cellular proliferation which leads to the blastema edification. PMID- 2881840 TI - Secretagogues for pancreatic hormone release in the channel catfish (Ictalurus punctatus). AB - We investigated the effect of several potential carbohydrate secretagogues, amino acids, a ketoacid, and potassium chloride on insulin, glucagon, and somatostatin release from the in vitro perfused Brockmann body of channel catfish (Ictalurus punctatus). Mannose (15 mM) stimulated the release of insulin and somatostatin. Fructose (30 mM) induced only a small and transient release of somatostatin. Galactose (15 mM) was not a secretagogue. Likewise, glyceraldehyde failed to stimulate hormone release. Among the amino acids newly tested, alanine and leucine, and also alpha-ketoisocaproic acid were without effect. A high concentration of potassium (25 mEq/liter) induced a pronounced release of insulin and glucagon and a moderate release of somatostatin. In conclusion, a striking similarity exists between catfish and higher vertebrates in their pancreatic endocrine response to hexoses; on the other hand, the catfish Brockmann body appears to respond only to a few of the common stimuli of pancreatic hormone release in mammals. PMID- 2881841 TI - Growth hormone secretion from chicken adenohypophyseal cells in primary culture: effects of human pancreatic growth hormone-releasing factor, thyrotropin releasing hormone, and somatostatin on growth hormone release. AB - A primary culture of chicken adenohypophyseal cells has been developed to study the regulation of growth hormone (GH) secretion. Following collagenase dispersion, cells were exposed for 2 hr to vehicle (control) or test agents. Human pancreatic (tumor) growth hormone-releasing factor (hpGRF) and rat hypothalamic growth hormone-releasing factor stimulated GH release to similar levels. GH release was increased by the presence of dibutyryl cyclic AMP. Thyrotropin-releasing hormone (TRH) alone did not influence GH release; however, TRH plus hpGRF together exerted a synergistic (greater than additive) effect, increasing GH release by 100 to 300% over the sum of the values for each secretagogue acting alone. These relationships between TRH and hpGRF were further examined in cultured cells exposed to secretagogues for two consecutive 2-hr incubations. TRH pretreatment enhanced subsequent hpGRF-stimulated GH release by about 80% over that obtained if no secretagogue was present during the first incubation. In other experiments, somatostatin (SRIF) alone did not alter GH secretion. However, SRIF reduced hpGRF-stimulated GH release to levels found in controls. Furthermore, GH release stimulated by the presence of both TRH and hpGRF was lowered to control values by SRIF. The results of these studies demonstrate that a primary culture of chicken adenohypophyseal cells is a useful model for the study of GH secretion. Indeed, these results suggest that TRH and hpGRF regulate GH secretion by mechanisms which are not identical. PMID- 2881842 TI - Characterization of melanin concentrating hormone in teleost hypothalamus. AB - Melanin concentrating hormone (MCH) is a heptadecapeptide isolated from chum salmon (Oncorhynchus keta) pituitaries. The peptide has been isolated from whole brain extract at a low yield of 1.2 micrograms/1300 brains. MCH activity in the hypothalamus was characterised by in vitro scale bioassay and radioimmunoassay. Specificity of these assay systems was examined with neurotransmitters such as epinephrine, norepinephrine, and dopamine, hypothalamic hormones such as somatostatin, isotocin, Arg-vasotocin, oxytocin, and Arg-vasopressin, and salmon prolactin and its chymotryptic peptide or salmon PRL176-187. Among them only salmon PRL176-187 exhibited weak activities in both assays. The neurotransmitters were 10(4) to 10(5) times less potent than MCH in the bioassay. MCH concentrations in a pituitary and a hypothalamus were estimated as 5300 +/- 750 ng (ca. 106 micrograms/g) and 48 +/- 9.5 ng (ca. 1.6 micrograms/g), respectively, by radioimmunoassay. Lysyl endopeptidase digestion of the hypothalamic extract resulted in a significant increase of biological activity as well as of immunoreactivity. Gel filtration of the hypothalamic extract and subsequent enzymatic digestion revealed that the fractions at higher molecular weight were contributory to the increase in the activities. PMID- 2881843 TI - Use of P-element-mediated transformation to identify the molecular basis of naturally occurring variants affecting Adh expression in Drosophila melanogaster. AB - The purpose of the work reported here is to identify the molecular basis of the difference in level of expression between the polymorphic Slow and Fast alcohol dehydrogenase (Adh) alleles in Drosophila melanogaster. Previous studies have shown that Fast lines typically have a two- to threefold higher activity level than Slow lines and they also have a substantially higher level of ADH-protein (estimated immunologically). The results of a restriction fragment length polymorphism study in relation to ADH activity variation had previously suggested that the difference in Adh expression between allozymes might not be due entirely to the amino acid replacement substitution, but could be due in part to linkage disequilibrium with a regulatory site polymorphism. Here we describe an approach that makes use of P-element-mediated transformation in order to identify the nucleotide substitution(s) responsible for this difference in ADH level. This approach consists of generating recombinants in vitro between Adh region clones derived from a typical Slow/Fast pair of alleles and then testing for the effects of particular restriction fragments on expression in vivo by transformation. Using this approach, the effect on both ADH activity and ADH-protein level clearly maps to a 2.3-kb restriction fragment that includes all of the Adh coding sequence and some intron and 3' flanking sequence, but excludes all of the 5' flanking sequence of the distal (adult) transcriptional unit. Comparison of Kreitman's DNA sequences for this fragment from several Slow and Fast alleles showing the typical difference in activity level shows that only three nucleotide substitutions distinguish all Fast from all Slow alleles. Thus, it is likely that one or more of these substitutions causes the major difference in Adh expression between allozymic classes. One of these substitutions is, of course, the Slow/Fast amino acid replacement substitution (at 1490) while the other two are nearby third position silent substitutions (at 1443 and 1527). A quantitative analysis of variation among transformant stocks shows that the P-element transformation approach can be used to localize even relatively small effects on gene expression (on the order of 20%). PMID- 2881844 TI - A plasmid vector for cloning and expression of gene segments: expression of an HTLV-I envelope gene segment. AB - We describe a cloning-expression vector system for selecting DNA fragments containing open reading frames (ORFs) and expressing them as beta-galactosidase (beta Gal) hybrid fusion proteins. The plasmid vector, pWS50, utilizes the very strong and easily regulated bacteriophage lambda promoter pL, and the efficient translation initiation signals of the N-terminal segment of the lambda cII gene. Fused distally to and out of translational phase with cII is the E. coli lacZ gene, lacking its own transcriptional and translational initiating signals. A unique restriction enzyme site (NruI) is located between the upstream regulatory sequences and the lacZ gene, which provides a cloning site for the insertion of blunt ended DNA fragments. In addition, there are two other unique restriction sites (NheI and BamHI) located in this region which can also be used as closing sites. If a DNA fragment does not contain any translation termination codons (i.e., an ORF), and is inserted correctly into the vector, the translational reading frame between cII and lacZ can be restored. Colonies containing these recombinants can be easily screened as LacZ+ on lactose indicator media. The beta galactosidase fusion proteins produced from the LacZ+ recombinants are identified on sodium dodecyl sulfate polyacrylamide gels by their large size and high level of production. To test the ORF cloning-expression system, a segment of the human T-cell lymphotrophic virus type I envelope gene was cloned and expressed at high levels. The envelope-beta Gal fusion protein was recognized by antibodies in serum from a patient with adult T-cell leukemia. PMID- 2881845 TI - Cloning and sequencing of papain-encoding cDNA. AB - Messenger RNA extracted from Carica papaya fruit was converted to cDNA and cloned into the PstI restriction site of plasmid pBR322. Subclones of the approximately 1.4-kb fragment were sequenced. The nucleotide sequence matched that expected, based on the amino acid (aa) sequence for papain, with the following exceptions: at aa positions 47, 118 and 135 the codon for glutamate was found instead of glutamine; at aa position 169 the codon for asparagine was found instead of glycine; at aa positions 86-88, a difference in the order of the aa codons was observed, namely tyr-pro-tyr instead of the published pro-tyr-tyr. The upstream sequence revealed that papain is probably synthesized with a 133-aa prosegment, suggesting that the enzyme is synthesized as an inactive zymogen. The downstream segment revealed an unusual (AT)9AGAA sequence beginning 26 bp from the double TGA stop codon. PMID- 2881846 TI - A 'Southern Cross' method for the analysis of genome organization and the localization of transcription units. AB - A 'Southern Cross' hybridization method is described which permits the rapid restriction mapping of DNA molecules, up to 40 kb in size, for at least ten enzymes in a single operation. The procedure allows the full set of 32P-end labelled fragments derived from one restriction enzyme digest to intersect and attempt to hybridize to the gel-separated fragments of as many as ten unlabelled digests immobilized on parallel sheets of filter paper. A two-dimensional array of hybridization spots is revealed on each recipient paper, indicating which radioactive and non-radioactive DNA fragments have sequences in common. A restriction map can then be directly and simply deduced from the matrix of hybridization spots in each cross-blot. The method affords advantages over other procedures for obtaining restriction maps in terms of the time required, the number of restriction enzymes that can be mapped, and the potential for eliminating ambiguity. It is also sufficiently sensitive to detect DNA rearrangements and restriction-site polymorphisms in moderately complex genomes. Furthermore, the procedure is applicable to other aspects of the study of genome organization: for example, the exon and intron areas of a segment of cloned genomic DNA can be identified by cross-hybridizing a set of radioactive restriction fragments from the genomic clone against immobilized RNA from a cell type of interest. PMID- 2881847 TI - Complete amino acid sequence of rat liver alcohol dehydrogenase deduced from the cDNA sequence. AB - Alcohol dehydrogenase (ADH) catalyzes the rate-determining reaction in the metabolism of ethanol. We report here the complete nucleotide sequence of a cDNA encoding rat liver ADH, and the deduced amino acid (aa) sequence of the protein. The rat enzyme contains a cluster of aa substitutions and an aa insertion in the region between aa residues 111 and 118, which is near the intron-exon junction reported for the human ADH gene. It also contains an additional cysteine in the highly variable region from aa residues 108-125 which may account for the unusual lability of rat ADH compared with ADH from other species. PMID- 2881848 TI - Managing the elderly patient with both hypertension and pulmonary disease. AB - Older patients with both hypertension and pulmonary disease pose a challenge to the physician. Satisfactory blood-pressure control must be achieved without exacerbating the concomitant pulmonary disease. Diuretics may interfere with mucus production and cause acid-base and electrolyte abnormalities. The beta adrenergic blocking agents should be avoided because of their risk of inducing bronchospasm. If a beta blocker must be used, it should be combined with an alpha and beta-adrenergic blocker, or an agent with intrinsic sympathomimetic activity or beta 1 selectivity. The direct and indirect vasodilators may be used safely in these patients, but the risk of worsening any underlying coronary artery disease must be kept in mind when prescribing either hydralazine or minoxidil. The calcium channel blockers and ACE-inhibitors have the best safety record in treating the elderly who have hypertension and COPD. For these patients, the calcium channel blockers offer the advantage of simultaneous therapy of coronary artery disease, whereas hypertensive patients with congestive heart failure would be more likely to benefit from an ACE-inhibitor. The ability to treat hypertension without precipitating unwanted adverse reactions or dangerous side effects is one of the arts of medicine. Fortunately, the range of drugs available to today's physician allows safe and efficacious treatment of the elderly patient who has both hypertension and pulmonary disease. PMID- 2881851 TI - Beta-thalassaemia in Campania: frequency of mutation identified by RSA I restriction enzyme: diagnostic aspects. PMID- 2881850 TI - Effect of intragastric pH on antral gastrin and somatostatin release in anaesthetised, atropinised duodenal ulcer patients and controls. AB - The synchronous change in the antral release of gastrin and somatostatin into a vein draining the stomach was studied during acidic and alkaline intragastric pH in six anaesthetised duodenal ulcer patients and six controls after atropinisation. No differences in the basal secretion of gastrin and somatostatin were observed among the two groups. Alkaline as well as acidic intragastric pH had no effect on the antral release of somatostatin in duodenal ulcer patients and controls. In contrast, alkaline intragastric pH was associated with a significantly higher antral gastrin release in duodenal ulcer patients than in controls. Acidic intragastric pH was associated with a significantly smaller inhibition of antral gastrin release in duodenal ulcer patients than in controls. These results suggest that atropinised anaesthetised duodenal patients release gastrin abnormally in the presence of acidic or alkaline intragastric pH and that any inverse relationship between antral gastrin and somatostatin release is uncoupled under these conditions. PMID- 2881849 TI - Effect of sulphasalazine and its metabolites on the generation of reactive oxygen species. AB - The relative in vitro anti-oxidant efficacy of sulphasalazine (salicylazosulphapyridine, SASP) and its metabolites (5-aminosalicylic acid, 5 ASA; sulphapyridine, SP) was examined by studying their effects on the generation of reactive oxygen species (ROS) using zymosan-stimulated polymorphonuclear leucocytes (PMNs) and a cell free, xanthine-xanthine oxidase system. Salicylazosulphapyridine, 5-ASA, and SP showed anti-oxidant effects to the various degrees. In particular, production of OH, which is one of the most potent reactive oxygen species, was remarkably suppressed by 5-ASA dose relatedly. These findings suggest that SASP and its metabolites play an important role in the inhibition of respiratory bursts. As the potent products of the respiratory burst by polymorphonuclear leucocytes are thought to be important inflammatory mediators, suppression of toxic reactive oxygen species generation by these agents may partly explain the therapeutic efficacy of SASP in ulcerative colitis, which is characterised by an acute mucosal inflammation dominated by polymorphonuclear leucocytes accumulation. PMID- 2881852 TI - [Cardioprotective properties of beta-blockers in patients after myocardial infarction]. PMID- 2881853 TI - [Alpha-adrenoceptor blocking action of terazosin]. AB - alpha-Adrenoceptor blocking activities and vascular relaxation activities of terazosin, a new antihypertensive agent, were studied. Terazosin had no effect on Ba2+, serotonin, angiotensin II and Ca2+ induced contractions in the isolated rat aorta. Terazosin competitively inhibited norepinephrine (NE) and phenylephrine (PE) induced contractions of the isolated rat aorta, and their pA2 values were 9.28 and 8.74, respectively. The potency of terazosin in the NE induced contraction was about 0.11, 8 and 176 times more than prazosin, phentolamine and yohimbine, respectively. The potency of terazosin in the PE induced contraction was about 0.09, 6 and 60 times more than prazosin, phentolamine and yohimbine. Terazosin (i.v.) competitively inhibited the PE induced pressor response. The "pA2" values of postsynaptic alpha-adrenoceptor blocking activity was 5.22, and its potency was about 0.05, 5 and 62.5 times more than prazosin, phentolamine and yohimbine, respectively. Terazosin (0.3 mg/kg, i.v. or less) did not show any significant effect on clonidine induced bradycardia during electrical stimulation of cardiac sympathetic nerve, whereas prazosin (0.3 mg/kg), phentolamine (0.1 mg/kg) and yohimbine (0.1 mg/kg) antagonized the effect of clonidine by 37%, 80.6% and 63.3%, respectively. Terazosin, 0.3 and 1 mg/kg, p.o., antagonized the PE (3 micrograms/kg, i.v.) induced pressor response in conscious unrestrained rats. This effect lasted for 8 hr in the case of 0.3 mg/kg and lasted for 12 hr in the case of 1 mg/kg. Thus, it is strong suggested that the antihypertensive effect of terazosin is based on the postsynaptic alpha-adrenoceptor blocking action. PMID- 2881855 TI - [Disorders of fat metabolism and atherosclerosis--prevention and therapeutic measures]. PMID- 2881857 TI - [Phased therapy and prognosis of peptic ulcer: a workshop. Nuremberg, 7-9 March 1986. Proceedings]. PMID- 2881854 TI - [Pharmacological studies of MO-8282, a new antidepressant]. AB - We investigated the pharmacological characteristics of MO-8282 as a novel antidepressant. MO-8282 inhibited the specific binding of 3H-clonidine to cerebro cortical membrane fractions from rats about five times more potently than mianserin, and it competed with clonidine in the twitch response of the isolated guinea-pig ileum under field stimulation. The results indicated that MO-8282 possessed alpha 2-adrenergic receptor blocking activity. MO-8282 in a dose of 30 mg/kg (p.o.) showed no inhibition against the uptake of noradrenaline, dopamine and serotonin in the rat brain, whereas mianserin inhibited the uptake of serotonin specifically. MO-8282, similar to mianserin, had no effect on spontaneous release of 3H-noradrenaline and slightly stimulated the release of 3H serotonin from the rat cerebrocortical synaptosome. The turnover rate of noradrenaline in rat brain was accelerated by administration of MO-8282 (30 mg/kg) for 15 days; however, that of dopamine and serotonin was not affected. The above findings indicate that MO-8282, unlike tricyclic antidepressants, mainly exerts alpha 2-adrenoceptor blocking action on the central noradrenergic system, similar to mianserin. In addition, the fact that MO-8282 unlike mianserin showed no inhibition against uptake of serotonin in brain suggests that the alpha 2 adrenoceptor blocking of MO-8282 is more specific and potent than that of mianserin. PMID- 2881856 TI - [Peptic ulcer--new trends]. PMID- 2881858 TI - [Factors influencing duodenal and stomach ulcer. Favorable and unfavorable conditions for incidence, healing, recurrence and prognosis]. PMID- 2881859 TI - [Protection of the gastric mucosa]. PMID- 2881860 TI - [Status of antacids in ulcer therapy]. PMID- 2881861 TI - [H2 blockers and acute peptic ulcer]. PMID- 2881862 TI - [The vagus nerve and ulcer disease]. PMID- 2881863 TI - [New prostaglandin derivatives--progress in ulcer therapy?]. PMID- 2881864 TI - [Will anti-ulcer drugs soon differ only in their side effects?]. PMID- 2881866 TI - [Combination possibilities in ulcer therapy]. PMID- 2881865 TI - [Magaldrate compared to ranitidine. The healing rate of stomach ulcer using magaldrate (100 mmol/d) versus ranitidine (300 mg/d)]. PMID- 2881867 TI - [Psychotherapy of peptic ulcer? Expectations and reality]. PMID- 2881868 TI - [Long-term drug therapy of peptic ulcer disease. A current review of the status of various anti-ulcer drugs]. PMID- 2881869 TI - [Staged therapy of peptic ulcer. Remarks on therapeutic programs]. PMID- 2881870 TI - [The dopamine receptor. Target of various diseases]. PMID- 2881871 TI - [Findings in the treatment of allergy]. PMID- 2881872 TI - Mechanisms involved in the depleting effect of cysteamine on pancreatic somatostatin. AB - We investigated the effects of cysteamine on the pancreatic islet hormones and found that pancreatic somatostatin contents depleted 60 min after the oral administration of cysteamine (300 mg/kg) to rats, yet the insulin and glucagon contents remained unchanged. When pancreatic islets isolated by collagenase digestion were incubated for 60 min in Krebs-Ringer bicarbonate buffer containing 0.1, 1, or 10 mM cysteamine, cysteamine dose-dependently decreased the somatostatin content, however, only a high concentration (10 mM) decreased the insulin level, and cysteamine exerted no effect on the glucagon content. The islet hormones (synthetic somatostatin-14, synthetic somatostatin-28, extracted pork insulin and extracted pork glucagon) were incubated for 60 min with cysteamine (0.1, 1, or 10 mM) and somatostatin-14 was found to be markedly decreased by 1 mM cysteamine. Pork insulin but not pork glucagon was dose dependently decreased by 0.1-10 mM cysteamine. Cysteamine, 0.1-1 mM, did not interfere with the radio-immunoassay system for somatostatin or insulin, although 10 mM cysteamine did so. This compound exerted no effect on the radioimmunoassay system for glucagon. Our studies support earlier findings that cysteamine administered to experimental animals plays a role of relatively specific depletor of somatostatin. The possibility that the depletion of somatostatin is in part due to the remarkable sensitivity of the intracellular compartments of the D cells to the drug and in part due to the remarkable sensitivity of the molecular structure of somatostatin has to be considered. PMID- 2881873 TI - The relationship of endocrine cells, dysplasia and carcinoembryonic antigen in Barrett's mucosa to adenocarcinoma of the oesophagus. AB - This study was undertaken to assess the prevalence and characteristic hormonal profile of endocrine cells in Barrett's mucosa and to determine to what extent this profile was shared by endocrine cells of adenocarcinomas arising therefrom. In addition, lower oesophageal carcinomas, not associated with columnar metaplasia, were examined to see if they exhibited a different hormonal profile. The patients studied comprised 43 who had had multiple oesophageal biopsies. 35 who had had oesophagogastric resection for adenocarcinoma arising in Barrett's mucosa and 26 in whom the resection showed no metaplastic epithelium adjacent to tumour. Argyrophil cells were present in 90% of biopsies and resections of Barrett's mucosa combined, irrespective of the histological type of metaplastic epithelium. By immunocytochemistry the most frequently identified substance in mucosal endocrine cells was serotonin (82%) followed by somatostatin (54%), secretin (22%) and pancreatic polypeptide (17%). Gastrin, bombesin, cholecystokinin, ACTH and substance P were not identified in metaplastic mucosa in any case. The difference in expression of serotonin by endocrine cells of tumours arising in Barrett's mucosa (31%) and those not (3.8%) was statistically significant (P less than 0.0186). Carcinoembryonic antigen (CEA) was demonstrated in 60% of oesophageal carcinomas, both endocrine positive and endocrine negative. Focal CEA expression was seen in 4.6% of biopsies and 14% of Barrett's mucosa adjacent to tumour. These results indicate a higher prevalence of endocrine cells in Barrett's mucosa than hitherto documented and suggest that serotonin may be a useful marker in distinguishing between primary oesophageal and putative gastric cancers at the gastro-oesophageal junction. The identification of CEA in oesophageal columnar epithelium is of little value in predicting the development of malignancy. PMID- 2881875 TI - [An approach to hygienic standards of learning work loads for students]. PMID- 2881874 TI - Polyadenylated and nonadenylated messenger RNA and androgen control of sexual behavior and scent marking in male gerbils. AB - To test the hypothesis that testosterone stimulates masculine social behaviors by inducing transcription of messenger ribonucleic acid (mRNA), we studied the effects of cordycepin, an adenosine analog that preferentially impairs synthesis of polyadenylated mRNA. When infused into the medial preoptic area of castrated male gerbils an hour before they received systemic injections of testosterone propionate, cordycepin almost completely blocked recovery of sexual behavior but did not affect recovery of scent marking. In gerbils given saline infusions, both behaviors were restored. When treatments were reversed, sexual activity resumed in males previously exposed to cordycepin and declined in males now receiving the drug. Cordycepin also blocked reinstatement of sexual behavior by the two major metabolites of testosterone, estradiol and dihydrotestosterone. Thus it does not suppress sexual behavior simply by suppressing synthesis of aromatase or 5 alpha reductase. Again, cordycepin had no effect on scent marking although this behavior is sensitive to other drugs that inhibit transcription or translation. The data suggest that testosterone may stimulate sexual behavior and scent marking, respectively, by inducing transcription of polyadenylated and nonadenylated mRNAs. PMID- 2881876 TI - [A case report of multiple endocrine neoplasia type I]. PMID- 2881877 TI - Localization and cloning of Xp21 deletion breakpoints involved in muscular dystrophy. AB - Twenty-nine deletion breakpoints were mapped in 220 kb of the DXS164 locus relative to potential exons of the Duchenne and Becker muscular dystrophy gene. Four deletion junction fragments were isolated to acquire outlying Xp21 loci on both the terminal and centromere side of the DXS164 locus. The junction loci were used for chromosome walking, searches for DNA polymorphisms, and mapping against deletion and translocation breakpoints. Forty-four unrelated deletions were analyzed using the junction loci as hybridization probes to map the endpoints between cloned Xp21 loci. DNA polymorphisms from the DXS164 and junction loci were used to follow the segregation of a mutation in a family that represents a recombinant. Both the physical and genetic data point to a very large size for this X-linked muscular dystrophy locus. PMID- 2881878 TI - A common restriction fragment length polymorphism of the human apolipoprotein E gene and its relationship to type III hyperlipidaemia. AB - We report a common DNA polymorphism of the apolipoprotein E (apoE) gene detected with the enzyme HpaI. In an individual who is heterozygous for the polymorphism, two hybridising fragments of DNA, one of 50 kb (the H1 allele) and one of 20 kb (the H2 allele) are detected. In 54 controls the frequency of the rare allele is 0.38 (PIC value 0.36). We have also studied the frequency of the polymorphism in normolipidaemic and hyperlipidaemic individuals whose apo E protein typing is known. In 39 individuals with type III hyperlipidaemia and the apo E phenotype E2E2, the frequency of the H2 allele is 0.97. In contrast, the frequency of the H2 allele in normolipidaemic individuals with the E2E2 phenotype is closer to that found in the general population. Possible explanations for this are discussed. PMID- 2881881 TI - Root surface caries symposium. PMID- 2881879 TI - DNA polymorphic patterns and haplotype arrangements of the apo A-1, apo C-III, apo A-IV gene cluster in different ethnic groups. AB - The allelic frequency of five different restriction fragment length polymorphisms (RFLPs) in the A-1, C-III, A-IV gene region has been determined in Caucasians, Negroes, Indian Asians, and Japanese. The polymorphic sites are with Taq-1 at the 5' end of the A-1 gene, with Msp-1 in the third intron of the A-1 gene, with Pst 1 in the intergenic sequence between the A-1 and C-III genes, with Sst-1 in the 3' non-coding region of the C-III gene, and with Pvu-II in the third intron of the C-III gene. The alleles identified by three of the RFLPs showed large differences in frequency amongst the races, especially between Caucasians and non Caucasians. Alleles of the Msp-1 polymorphism and Sst-1 polymorphism, which were rare in Caucasians (frequencies 0.03 and 0.01), were more common in Japanese (frequencies 0.37 and 0.35), Indian Asians (frequencies 0.37 and 0.26), and Negroes (frequencies 0.31 and 0.31). In contrast with a Pvu-II polymorphism one allele was rare in Japanese and in Indian Asians (frequency 0.01) but more common in Caucasians (frequency 0.11). Linkage disequilibrium was evident between some of the alleles and a total of seven haplotypes were identified among the different races. PMID- 2881880 TI - Three-point linkage analysis employing C3 and 19cen markers assigns the myotonic dystrophy gene to 19q. AB - In seven large families with myotonic dystrophy (DM) comprising 102 individuals, linkage studies were performed employing restriction fragment length polymorphisms in the complement component 3 gene and the 19cen C banding heteromorphism as genetic markers. Three-point linkage analysis excludes DM from the 19cen-C3 segment and strongly supports its assignment to the proximal long arm of chromosome 19. PMID- 2881882 TI - The use of multiple restriction fragment length polymorphisms in prenatal risk estimation. II. Conditional risk distributions. AB - Although analytical procedures for multiple marker risk estimation are now well established, we still lack a unified optimal procedure for deciding which family members to examine and which markers to use. Towards this goal, the application of conditional risk distributions is developed, along with a suggested statistic for judging the utility of a marker. The conditional risk distribution depends on what knowledge has already been obtained about the pedigree, and indicates the expected outcome of risk estimates after another marker is examined. Population genetic aspects including haplotype frequencies, linkage disequilibrium, family size and pedigree structure and the statistical confidence in the linkage map all influence the optimal strategy for multiple marker risk estimation. PMID- 2881883 TI - A new polymorphic marker of the T-cell antigen receptor alpha chain genes in man. AB - The restriction fragment length polymorphism of the unrearranged T-cell antigen receptor (Tcr) alpha chain gene was investigated. Taq I digests, when probed with a Tcr alpha chain cDNA probe, revealed polymorphic bands of 7.0, 2.0, and 1.4 kb, due to variations around the C alpha gene, and the V gene cluster. Family studies confirmed the segregation of these polymorphic bands as allelic markers. These polymorphisms provide a new marker for the analysis of genetic variation of the Tcr alpha chain, and the influence of variation of the Tcr genes on the immune response. PMID- 2881884 TI - Polymorphisms of DQ beta genes in HLA-DR4 haplotypes from healthy and diabetic individuals. AB - The restriction fragment length polymorphism (RFLP) of DQ beta was assessed in a panel of control and insulin-dependent diabetes (IDD) patients who were serologically typed as HLA-DR4 homozygotes or HLA-DR3, DR4 heterozygotes. Digestions of genomic DNA with Bam HI, Bgl II, Pst I, Xba I, and Hind III revealed a total of 15 RFLPs in the panel of 71 HLA-DR4 chromosomes. These RFLPs were organized into six allelic groups on the basis of segregation analysis in families. Complete RFLP haplotypes for the 5 restriction enzymes could be constructed for 42 of the HLA-DR4 chromosomes. This analysis revealed 18 RFLP haplotypes of DQ beta associated with the DR4 chromosomes tested. Two of these haplotypes, designated DQ3.DR4. a and DQ3.DR4.b, accounted for over 50% of the DR4 chromosomes analyzed. These two haplotypes were antithetical for the RFLPs detected by all five enzymes, indicating that they represent very distinct forms of DQ beta. The remaining 16 haplotypes were infrequent or unique and were closely related to either a DQ3.DR4.a or DQ3.DR4.b. Two of the RFLPs detected, a 5.8 kb Bgl II fragment and a 10.5 kb Bam HI fragment, had increased frequencies in disease-associated chromosomes. However, none of the RFLPs we detected exhibited a statistically significant increase in IDD or control populations. In contrast, the DQ3.DR4.b DQ beta haplotype was significantly decreased in IDD associated DR4 chromosomes (P = 0.04). These results suggest that the DQ3.DR4.b DQ beta allele may be protective for the development of IDD. PMID- 2881885 TI - Restriction fragment length polymorphism at the HLA-C locus. AB - We have used the HLA-C-specific DNA probe pC250 to investigate restriction fragment length polymorphism (RFLP) at the HLA-C locus. Genomic Southern blot hybridization included DNA prepared from a panel of homozygous typing cells representing serological specificities Cw1 to Cw8 and also from samples representing Cw blanks. Although many restriction nucleases failed to reveal any polymorphism, RFLPs were evident with Taq I, Pvu II, Bst XI, Nde I, and Nci I in addition to the previously reported Eco RI. In the case of Bst XI, a unique RFLP defined a subset of serologically defined Cw blanks. Comparison of RFLP sizes with restriction fragment lengths obtained from the known HLA-Cw3 gene sequence permitted the localization of intragenic C locus RFLPs and the identification of a variable Taq I site in the second intron, a variable Nci I site near the end of the fourth exon, and a variable Pvu II site in the fifth intron. PMID- 2881886 TI - Human immunoglobulin variable region genes: a new VH sequence used to detect polymorphism. AB - A human heavy chain variable region subgroup III pseudogene (HV3.3) was isolated, characterized, and sequenced. When HV3.3 was hybridized to Southern blots of human DNA, two potentially informative polymorphic bands, resulting from 2.7 kb Hind III (HH2.7) and 7.3 kb Eco RI (HE7.3) fragments, were detected with frequencies of 0.553 and 0.606, respectively. These polymorphic bands showed Mendelian segregation in families and appeared to be in tight linkage disequilibrium with each other (chi 2(1) = 24.91, P less than 0.001). Evidence from sibling-pair data indicated linkage of the Hind III polymorphic band to constant region allotypic and restriction fragment length polymorphism markers. Bands representing alternative forms of the polymorphic restriction sites were not detected for either HH2.7 or HE7.3. This indicates either that the alternative fragments comigrate with homologous fragments resulting from conserved restriction sites, or that the polymorphism is due to a gene duplication or deletion. No band segregating with HH2.7 was found in separate digests using eight other enzymes. Although this indicates that a major deletion or unlikely, it does not exclude the possibility of a gene deletion or duplication affecting the intergenic region(s) of one or more homologous genes. Whatever the precise explanation, these findings support the hypothesis that there is polymorphic variation of VH gene repertoires in man. PMID- 2881887 TI - Human immunoglobulin variable region genes: V kappa polymorphisms suggest variation in V-gene repertoires. AB - The present study characterizes four potentially informative polymorphic bands of 5.2, 2.3, 1.9, and 1.2 kb, detected by Southern blot hybridization of Eco RI digests of human DNA using HK101/80 (an immunoglobulin V kappa I probe). These restriction fragment length polymorphisms (RFLP) show Mendelian segregation and they are linked to each other and to Km(1), the allotypic marker on the kappa constant region. There is strong linkage disequilibrium between the 2.3 and 1.2 kb polymorphisms. A 0.7 kb Pst I polymorphic band and a 2.9 kb Sac I polymorphic band were also identified; the latter may reflect a region of tandem repeats in the V kappa region. No bands representing the alternative forms of any of the polymorphic restriction sites were identified. This implies either that genes are missing from the V kappa repertoire or that such bands are hidden because of comigration of fragments due to conservation of restriction sites. Evidence for comigration of fragments was obtained from independent V kappa clones and suggests that dark bands on Southern blots of Pst I digests must often represent several superimposed genes which have conserved restriction sites. The demonstration of RFLP within the V kappa region provides circumstantial evidence for polymorphic variation in the repertoire of V kappa structural genes. The RFLP reported here should be useful as genetic markers in future studies on the immune response and disease susceptibility in man. PMID- 2881888 TI - Mouse candidiasis. II. Host responses are T-cell dependent and regulated by genes in the major histocompatibility complex. AB - Administration of a Thy-1.2-specific monoclonal antibody to BALB/c mice resulted in a significant decrease in the efficiency of clearance of Candida albicans from the spleen. The rate of clearance of organisms from the spleen of congenic mice was determined by genes in the major histocompatibility complex, as was the magnitude of the inflammatory response in the popliteal lymph node after footpad immunization. These results formally demonstrate the involvement of T cells in host responses to primary candida infection. PMID- 2881889 TI - Polymorphism and mapping of the complement gene C4 in the rat. PMID- 2881890 TI - The activity of gamma-glutamyl transpeptidase in the small intestine of some species of animals at different stages of growth. AB - The activity of gamma-glutamyl transpeptidase (GTP), the key enzyme of gamma glutamyl cycle, was studied in the intestine of new born, suckling and adult animals (rats, mice, guinea pigs and rabbits). In all the four species, the activity of GTP was greater in new borns than in adults. The activity was highest in rats and almost negligible in guinea pigs. PMID- 2881891 TI - The effect of protein deficiency on the activity of gamma-glutamyl transpeptidase in the small intestine of rats. PMID- 2881892 TI - Distribution of specific DNA sequences among pathogenic and commensal Neisseria species. AB - Several traits, including pili and the outer membrane proteins P.II and H.8, have been associated with pathogenic Neisseria species. We examined several Neisseria species for DNA sequence homology to cloned pilin, P.II, and H.8 genes. Strains of Neisseria gonorrhoeae and N. meningitidis showed hybridization to all of these genes. Commensal strains showed little hybridization to any of these genes. Strains of N. lactamica and N. cinerea showed intermediate patterns of hybridization. Generally, organisms that expressed a given trait showed DNA homology to the corresponding cloned gene. However, we observed pili on some commensal strains that did not show hybridization to the cloned gonococcal pilin gene. PMID- 2881894 TI - Use of monoclonal antibodies to probe subunit- and polymer-specific epitopes of 987P fimbriae of Escherichia coli. AB - The relationship between the structure and biological function of 987P fimbriae of a strain of enterotoxigenic Escherichia coli (O9:K103:H-) from piglets was investigated. A set of four monoclonal antibodies was prepared from the spleen cells of mice immunized with isolated 987P fimbriae. Antibodies E11, D5, and C3, but not G10, reacted in enzyme-linked immunosorbent assays with 987P fimbriae bearing E. coli. Electron microscopy showed that E11 and D5 reacted in a discrete periodic pattern forming a spiral motif along the length of the fimbriae. The results of enzyme-linked immunosorbent assays were in agreement with these results; antibodies E11 and D5 reacted at a high dilution (1:12,000) with native fimbriae on the surface of E. coli, whereas antibody C3 reacted at an intermediate dilution (1:3,000) and G10 failed to react at all (less than 1:250). In contrast, C3 and G10 reacted at a dilution of 1:3,276,000 with the fimbrial subunits derived by treating the isolated fimbriae with 6 M guanidine hydrochloride, whereas E11 and D5 reacted with the subunits at much lower dilutions of 1:800 and 1:6,400, respectively. Moreover, fimbriae reassembled from the subunits regained reactivity with antibodies D5 and E11, indicating that these antibodies are directed against quaternary conformational epitopes. Only the three antibodies (D5, E11, and C3) that recognized epitopes accessible on intact fimbriae were able to efficiently block the adhesion of 987P fimbriated E. coli to piglet enterocytes. These results indicate that certain epitopes of 987P fimbriae are dependent on quaternary structural conformation, whereas others are present on monomeric subunits; some of the latter appear to remain accessible on fully assembled fimbriae. PMID- 2881893 TI - Purification and characterization of serotype 6 fimbriae from Bordetella pertussis and comparison of their properties with serotype 2 fimbriae. AB - Fimbriae were removed from Bordetella pertussis (serotype 1.3.6) by mechanical shearing and purified by precipitation with ammonium sulfate, pH-dependent precipitation at pH 7.4, followed by two successive extractions of the precipitated fimbriae with 4 M urea. By electron microscopy, the precipitated fimbriae appeared as aggregated bundles of long, relatively straight filaments which were disaggregated to individual flexuous filaments at pH 10.5. These purified fimbriae were identified as serotype 6 agglutinogens, since antibody to the purified fimbriae agglutinated B. pertussis strains serotyped as 1.3.6, 1.2.3.6, or 1.2.3.4.6 but did not agglutinate strains of serotype 1.2.3.4, 1.2.3, or 1.3. In contrast, antibody to serotype 2 fimbriae only agglutinated B. pertussis strains containing serotype 2 agglutinogen. Purified type 6 and 2 fimbriae were found to be weakly cross-reactive by enzyme-linked immunosorbent assay, using polyclonal antibody to each type of fimbria. In an immunoblot assay, polyclonal antibodies to a 22,000-dalton subunit of fimbriae from B. bronchiseptica reacted strongly with the type 2 fimbrial subunit of B. pertussis, but only weakly with the type 6 subunit. When subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis, the protein subunit of the type 6 fimbriae migrated with a molecular weight of 21,500, whereas the type 2 fimbrial subunit had a molecular weight of 22,000. The two types of subunits had similar amino acid compositions and showed amino-terminal sequence homology in 15 of 21 amino acids. The amino-terminal amino acid sequences of the B. pertussis fimbriae were distinct from those reported for fimbriae from other gram-negative bacteria. Neither the type 6 nor the type 2 fimbriae caused hemagglutination when assayed with several types of erythrocytes. PMID- 2881896 TI - Plasma gamma glutamyltransferase levels during rifampicin therapy for tuberculosis. AB - A possible effect of rifampicin enzyme induction on microsomally derived plasma gamma glutamyltransferase (gamma GT) during treatment for tuberculosis patients with spinal bone disease and pulmonary or lymph node involvement was studied. Of 10 patients with bone disease 5 had raised levels prior to therapy (greater than 60 IU/l) and none were alcohol consumers. Gamma GT is not known to be present in bone and this probably represents an indirect effect on the liver. Changes in gamma GT in the first 2 months of rifampicin/isoniazid treatment were variable and will not serve as an index of response to therapy. Of 69 patients with lung or lymph node disease 15 had raised levels during treatment and 9 had a high alcohol intake, when the alcohol group were excluded there was no significant difference from controls who had completed treatment (p greater than 0.1). We conclude that plasma gamma GT, a standard clinical estimation of liver dysfunction, is a useful index of suspicion for alcoholics among the tuberculous group but the disease itself can produce similar levels. It did not reflect the known hepatic microsomal inducing properties of rifampicin and thus differs from the anticonvulsant model. Clinical value would be enhanced if specific liver isoenzymes in plasma were identified which separated tissue injury, enzyme induction and the effect of extrahepatic infection on the liver. PMID- 2881895 TI - Membrane glycoproteins of human polymorphonuclear leukocytes that act as receptors for mannose-specific Escherichia coli. AB - Type 1 fimbriated (mannose-specific) Escherichia coli cells bind to mannose residues on human polymorphonuclear leukocytes (PMN); this leads to phagocytosis of the bacteria. To identify the mannose-containing receptors on the PMN, the cells were surface labeled with 125I and lysed in 0.5% Nonidet P-40, and the lysate was fractionated by affinity chromatography on a column of Sepharose-bound fimbriae. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography of the material eluted from the column with 500 mM methyl alpha-mannoside revealed two radioactive bands of Mr 70,000 to 80,000 (gp70-80) and 100,000 (gp100). Another weak band of Mr 150,000 (gp150) was observed after prolonged exposure of the gel. Upon blotting of the glycoproteins separated by polyacrylamide gel electrophoresis and overlaying of the blots with concanavalin A, gp150 appeared as the major band. Membrane preparations of the PMN were enriched in gp70-80, gp100, and gp150, in comparison with the cell homogenates, further suggesting that these glycoproteins are surface components. Fractionation of the membrane preparations on the immobilized fimbriae followed by concanavalin A overlay of blots of the methyl-alpha-mannoside-eluted material revealed that gp150 was the major component in this fraction. The eluted fraction, obtained from a cell lysate (4.4 micrograms/ml), inhibited by 70% the agglutination of yeasts by the intact bacteria. Our results suggest that the three surface glycoproteins isolated by us serve as receptors for mannose-specific E. coli on PMN and may be involved in the lectin-mediated phagocytosis of the bacteria. PMID- 2881897 TI - Evaluation of a new bronchodilating compound (broxaterol) administered as a pressurized aerosol. AB - The bronchodilating activity and the tolerability of a new beta 2-agonist, broxaterol hydrochloride, administered in single doses of 200 and 400 micrograms as pressurized aerosol were studied in 12 adult patients with reversible airway obstruction, taking placebo as a control. A double-blind three-way cross-over design using a series of randomly chosen latin squares was employed. FVC, FEV1, MMEF, heart rate, and blood pressure were measured immediately before and 7.5, 15, 30, 60, 120, 180, and 240 min after each treatment. Our results show that broxaterol is an effective bronchodilating drug with a dose-related activity. The areas under the curves of the changes in FVC, FEV1, and MMEF after the 400 micrograms dose were found to be significantly greater as compared to the 200 micrograms dose. Both broxaterol doses produced significant increases in all the spirometric indices already at the first measurement, i.e., 7.5 min after treatment. Broxaterol 400 micrograms induced significant increases in FVC, FEV1, and MMEF through at least 4 h. The tolerability of the new compound was good. PMID- 2881898 TI - Interactions of dihydroergotamine with etilefrine in human leg veins in vitro and in situ. AB - The aim of the present study was to provide evidence for an interaction of dihydroergotamine (DHE) and etilefrine (Et) with regard to their constrictor effect on human leg veins both in vitro and in situ. In isolated strips of the femoral vein, DHE exerted a concentration-dependent sustained contraction which also continued after washing out the preparation. Et induced a reversible contraction of the strip at considerably higher concentrations as compared to DHE and noradrenaline. When DHE (0.01 mumol/l) and Et (6 mumol/l) were simultaneously applied, there was only an additive venoconstrictor effect. The influence of DHE and Et on the compliance of dorsal foot veins was studied in 14 male volunteers by means of a variable differential transformer. In the short-term experiment, an oral dose of 10 mg DHE was ineffective, whereas after the subcutaneous injection of 1 mg DHE a significant venoconstrictor effect was observed. Et, orally given in a dose of 10 mg, was also ineffective, while 20 mg Et caused a short-lasting effect which could not be augmented by the concurrent intake of 10 mg DHE. When 10 mg Et were administered 30 or 60 min after a single oral dose of 10 mg DHE, a distinct venoconstrictor effect occurred. These findings suggest that no pharmacodynamic synergism of the two drugs can be expected when DHE and Et directly act on the veins. The augmentation of the venoconstrictor in situ effect of Et after pretreating the volunteers with DHE could result from an amelioration of the oral bioavailability of Et by DHE, i.e., from a pharmacokinetic interaction of the two drugs. PMID- 2881899 TI - Labetalol in the treatment of angina pectoris. AB - The present review shows that labetalol has many advantageous properties in the treatment of patients suffering from angina pectoris with or without hypertension. These patients respond with vasoconstriction to a variety of internal and external influences. The selective alpha 1-blocking component in addition to the non-selective beta-blockade of labetalol attenuates the increased coronary vascular resistance and improves coronary haemodynamics especially under stress in a manner which should be favourable in myocardial ischaemia. In addition, the alpha 1-blocking component may prevent different kinds of arrhythmias generated by alpha-adrenoceptor stimulation. Labetalol has no effect on renal blood flow, glomerular filtration rate, plasma electrolyte concentrations, glucose tolerance, lipoprotein cholesterol ratio, renin angiotensin-aldosterone system, uric acid levels, or on platelet aggregation. Intravenously administrated labetalol has proved to be effective in patients with acute myocardial infarction, especially if associated with hypertension. In order to avoid postural hypotension, oral treatment should be started with a low dose of 100 mg twice daily. The usual dosage in patients without hypertension is 200 mg twice daily, but in patients with hypertension doses up to 1200 mg or even more have been used. In low doses up to 400 mg daily, the unwanted effects are few and often self-limited. High doses can cause side effects related to both beta- and alpha-blocking properties of labetalol. As an antianginal agent labetalol has proved to be at least as effective as selective or non-selective beta-blockers. PMID- 2881900 TI - Effect of beta-adrenoceptor blockade and calcium antagonism, alone and in combination, on thermoregulation during prolonged exercise. AB - The effect of clinically used doses of propranolol, atenolol, nifedipine, propranolol plus nifedipine, and atenolol plus nifedipine on thermoregulatory responses of 11 healthy men was studied during 2-h block-stepping in heat. Drug intervention did not alter ventilation during exercise. In contrast, propranolol and atenolol produced equivalent reductions in exercise tachycardia, implying a similar level of beta 1-adrenoceptor blockade. The heart rate response to exercise was unaffected by nifedipine and during dual beta-adrenoceptor blockade and calcium antagonism was equivalent to that with beta-adrenoceptor blockade alone. While rectal temperature rises were not modified by drug ingestion, propranolol and, to a lesser degree, atenolol and combination therapy, but not nifedipine alone, attenuated skin temperature rises. Moreover, although atenolol, nifedipine, and their combination did not alter sweating, propranolol and its combination with nifedipine enhanced sweating during the 1st and 2nd h of exercise. This study concludes that nifedipine does not modify thermoregulation during exercise and allows for greater confidence of its use during cardiac rehabilitation. Furthermore, the present data confirm that propranolol does enhance sweating during exercise and demonstrate that this effect is not mediated simply by an earlier onset of rapid sweating nor abolished by concomitant calcium antagonism. PMID- 2881901 TI - Comparison of continuous and intermittent multistage maximal exercise testing during beta-adrenoceptor blockade in physically active men. AB - Cardiorespiratory responses of 11 healthy males were studied, with placebo and propranolol, during a continuous and an intermittent multistage maximal treadmill test. With placebo, equivalent maximal heart rates were attained for the disparate test modes, and the intermittent protocol yielded a slightly higher (2%, P less than 0.01) maximal O2 consumption. In contrast, during beta adrenoceptor blockade, higher maximal heart rates (5.1%, P less than 0.01) and O2 consumptions (4.4%, P less than 0.02) were reached with intermittent compared with continuous testing. Values were, however, markedly lower (P less than 0.001) for both protocols than with placebo. These results demonstrate that the precise degree of attenuation of maximal heart rate and O2 consumption observed in physically active persons receiving propranolol is partly dependent upon the actual test protocol utilized. Furthermore, the present data suggest an advantage for intermittent testing when accurate evaluation of the maximal cardiorespiratory capacity is desired in such individuals. PMID- 2881902 TI - Ecstacy: a review of MDMA and MDA. AB - The Drug Enforcement Administration classified the drug methylenedioxymethamphetamine, MDMA, also known as Ecstacy, as a Schedule I controlled substance on July 1, 1985. The controversy surrounding the classification of MDMA is related to the question of its efficacy as an adjunct to psychotherapy and the larger issue of how to regulate the production and use of designer drugs. The authors review the literature on MDMA and its predecessor, MDA, a substance that differs from MDMA by one methyl group. PMID- 2881903 TI - Molecular characterization of 125I decay and X-ray-induced HPRT mutants in CHO cells. AB - The predominant initial lesion induced by 125I decay in DNa is a double-strand DNA break comprising a 'mini deletion' of up to several base pairs (bp). However, Southern analysis of the structure of 125I decay-induced HPRT mutants in Chinese hamster ovary cells revealed that most of the mutants are deletions of thousands of bps. A similar predominance of substantial deletions was also found in X-ray induced mutants. PMID- 2881905 TI - Human amoebiasis: cultivation and experimental transmission in animals. AB - In vitro cultivation was carried out on an initial strain of Entamoeba histolytica from human source. Dysphasic medium was used and concentrations of horse serum and antibiotic varied in response to developments. Experimental infection of dogs, rabbits and mice was carried. Except for the controls, all animals were orally infected and monitored until the experiment was terminated. Parasitaemia became evident as from the 6th day in dogs experimentally infected and until about the 20th day when lower parasitaemia were obtained. Characteristic erosions were observed at autopsy. The tests in rabbits and mice showed that the strain used in this experiment was virulent. This paper highlights both the virulent nature of this parasite on other animals and its zoonotic potential. PMID- 2881904 TI - Radioactive colloidal gold as a tool to quantify extravasation of macromolecules in the rat cremaster muscle. AB - Since previously described simple methods were too insensitive to quantify the extent of microvascular permeability increase in the rat cremaster muscle, we applied a new quantitative technique using radioactive colloidal gold (198Au) as the macromolecular tracer. Dose-response effects on microvascular permeability were found with increasing doses of subscrotally injected serotonin or histamine. The presence of colloidal gold particles in the subendothelial space of the postcapillary venules, as verified ultrastructurally, indicated endothelial permeation of the tracer macromolecules. The increased permeability elicited by serotonin was inhibited in a dose-dependent way by serotonin receptor antagonists (potency: methysergide greater than or equal to ketanserin = ritanserin greater than cinanserin), suggesting the presence of functional S2-serotonergic receptors on postcapillary venular endothelial cells. A dose-related inhibition of the histamine-induced extravasation was seen with the H1 antagonists astemizole and azatidine (astemizole greater than azatidine); the H2 antagonists cimetidine and ranitidine had no inhibitory effect. The radioactive colloidal gold technique is a sensitive and reliable tool for pharmacological experiments aimed at investigating the extravasation phenomenon in small tissue samples such as the rat cremaster muscle. PMID- 2881906 TI - Beta-thalassemia: analysis of mRNA precursors of a mutant human globin gene with defective splicing using peripheral blood nucleated red blood cells. AB - Studies on the effects of thalassemic mutations on gene function in vivo have clinical as well as scientific implications. Usually these studies have been performed on nucleated red blood cell (RBC) precursors normally present in bone marrow. Many patients with beta-thalassemia are splenectomized and may have high levels of nucleated RBC, orthochromatic normoblasts, in their peripheral blood (1 5% of total RBC). The possibility of exploiting these cells instead of bone marrow as a source for nuclear and cytoplasmic RNA for expression studies was investigated. A simple procedure was developed for enrichment for normoblasts in blood samples withdrawn from patients prior to transfusion. Globin transcripts were analyzed in RNA purified from 12 patients. Unspliced precursor beta-mRNA molecules were observed in a patient with beta o-thalassemia, homozygous for a mutation at the 5' IVS2 splice site of the beta-globin gene. Detailed analyses showed that his mature beta-mRNA was larger than normal, and that a cryptic 5' splice site, approximately 50 nucleotides downstream from the normal one, was utilized. We conclude that peripheral blood can be used as a reliable source of RNA for the analysis of the effects of beta-thalassemia mutations on gene expression and the relationship to the clinical condition. Moreover, this procedure facilitates the comparison of in vivo gene expression with the results obtained from DNA transfection experiments with cloned beta-thalassemia genes. PMID- 2881907 TI - Certification for medical assistants. PMID- 2881908 TI - Contract vigilance. PMID- 2881909 TI - Peritonitis and small bowel obstruction. PMID- 2881910 TI - Aortic coarctation with complete occlusion. PMID- 2881911 TI - Pleural placement of the Swan-Ganz catheter. PMID- 2881912 TI - IMJ interview: Medicine meets the media. PMID- 2881913 TI - Midline scrotal ablation technique for unilateral cryptorchid castration in horses. AB - Thirty-nine unilateral cryptorchid horses were castrated, using a midline scrotal ablation technique. This approach was satisfactory to access both inguinal rings, to eliminate the need for 2 incisions, and to allow for completion of the surgery by primary closure. These horses recovered from surgery with few complications, returned to work promptly, and had excellent cosmetic results. PMID- 2881914 TI - Retrovirus produced by a lymphoid cell line from an infant with acute lymphoblastic leukemia. AB - A lymphoid cell line CK-a was established from peripheral blood of an infant with acute lymphoblastic leukemia of non-T, non-B cell type with mediastinal tumor. The CK-a cells were positive for surface immunoglobulins, Epstein-Barr virus specific nuclear antigen, HLA-DR and Leu 12 antigens, and negative for sheep erythrocyte-rosette-receptor, and Leu 1, 2, 3 and 4 antigens. Budding particles were detected in electron micrographs of ultrathin sections of the CK-a cells. In the culture media of CK-a cells, particles with a buoyant density of 1.16 g/ml and labeled with [3H]uridine and [35S]methionine but not with [3H]thymidine were found to carry reverse transcriptase activity which preferred Mg2+ to Mn2+. Enveloped particles of 80 to 120 nm in diameter were detected in the fractions at 1.16 g/ml by electron microscopy. Thus, the particles had properties compatible with a definition of Retroviridae, and were tentatively named CK virus (CKV). The genome size of CKV RNA determined by agarose-acrylamide composite gel electrophoresis was 6.1 +/- 0.2 kb. Immune electroblotting assay detected antibody reactive with a CKV protein with a molecular weight of 67,000 in the serum of the patient, but not in sera of an adult T cell leukemia patient and healthy controls. No syncytia were formed by mixed cultures of CK-a and XC cells. PMID- 2881915 TI - Differences in adhesiveness among type 1 fimbriate strains of Enterobacteriaceae revealed by an in vitro HEp2 cell adhesion model. AB - Ten type 1 fimbriate strains of Enterobacteriaceae were examined in an in vitro adhesion assay with HEp2 epithelial cells. The range of HEp2 cell adhesiveness, which was characteristic for each strain, was affected by motility, type 1 fimbriation and production of mannose sensitive haemagglutinin. Nevertheless, not all type 1 fimbriate strains adhered well in this model. The findings are discussed with regard to the possibility that different type 1 fimbriate enterobacteria, though all are mannose sensitive, recognize different mannose containing receptors present or available on the surfaces of the HEp2 cells. PMID- 2881916 TI - Nonuniform effects of histamine on small pulmonary vessels in cats. AB - In in vivo cat lung, using an X-ray TV system, we analyzed responses in internal diameter (ID), flow velocity, and volume flow of arteries and veins (100-500 microns ID) to histamine (8-15 micrograms/kg iv) under three conditions. With histamine alone, three types of ID response (constriction, dilatation, and no change) occurred in parallel-arranged arteries. Relative frequency and magnitude of constriction were maximum in arteries of 300-400 micron ID, whereas those of dilatation were maximum in arteries of 100-200 micron ID. In veins, relatively uniform constriction occurred. Under H2-blockade, histamine caused greater constriction than that with histamine alone in arteries and veins of 300-500 micron ID. Under beta-blockade, with histamine, ID of all vessels decreased significantly below the ID sizes under the above two conditions, and no dilatation occurred. In two parallel arteries that showed opposite ID changes to histamine, flow velocity increased, but volume flow decreased in a constricted artery while it increased in a dilated one. Those data indicated that, with histamine, qualitatively and quantitatively nonuniform ID response was induced in both parallel- and series-arranged small pulmonary arteries and, in turn, produced heterogeneous flow distribution. Factors to cause the nonuniformity may be partly explained by difference in density of H2- and beta-receptors in vascular walls. PMID- 2881917 TI - Parasympathetic involvement in PAF-induced contraction in canine trachealis in vivo. AB - We studied the contractile response elicited by platelet-activating factor (PAF) administered intra-arterially into the tracheal circulation of 34 dogs in vivo. A method that avoided tachyphylaxis encountered in prior investigations was developed for isometric measurement of multiple dose-response effects. PAF was a very potent contractile agent; active tension was elicited with 10(-11) mol ia PAF. To determine the mechanism by which contraction was induced, dose-response curves were generated in groups of five animals each treated with either 0.5 mg/kg (approximately 1.5 X 10(-5) mol) iv + 10(-3) mg/kg (3 X 10(-8) mol) ia atropine, 5 mg/kg iv indomethacin (INDO), or 7.5 mg/kg iv hexamethonium (HEX). After pretreatment with atropine, contraction still was elicited with 10(-11) mol ia PAF. However, maximal contraction was only 16.2 +/- 2.74 g/cm (vs. 35.7 +/- 5.74 g/cm for untreated controls; P less than 0.02). The dose at which maximal contraction was elicited after atropine was 10(-7) mol ia (vs. 1.9 X 10(-9) mol for controls; P less than 0.001). Pretreatment with INDO caused minimal attenuation, and HEX had no effect on the response elicited by ia PAF. We demonstrate a method for assessing the effects of PAF in central airways that avoids tachyphylaxis and permits dose-response studies in the same animal. We also demonstrate that PAF is an extremely potent mediator that elicits tracheal smooth muscle contraction at least in part by postganglionic activation of parasympathetic nerves. A direct contractile effect of PAF which is not related to secretion of products of the cyclooxygenase pathway is also suggested. PMID- 2881919 TI - Identification of Tn4451 and Tn4452, chloramphenicol resistance transposons from Clostridium perfringens. AB - The recombinant plasmids pJIR45 and pJIR97 contain the chloramphenicol resistance determinants derived from the Clostridium perfringens R plasmids pIP401 and pJIR27, respectively. Escherichia coli cultures which harbored these recombinant plasmids rapidly became chloramphenicol sensitive when grown in the absence of chloramphenicol. The loss of resistance was associated with the loss of 6.2 kilobase (kb) segments from both plasmids. Detailed restriction analysis of E. coli- and C. perfringens-derived deletion plasmids indicated that deletion of these segments was essentially precise. Transposition of the 6.2-kb segments was demonstrated by cloning the determinants into a temperature-sensitive plasmid, curing the recombinant plasmids, and selecting chloramphenicol-resistant, plasmid free clones. Southern hybridization analysis of chromosomal DNA isolated from these recA E. coli clones indicated that the 6.2-kb segments had transposed to different sites on the chromosome. Heteroduplex analysis and restriction mapping indicated that the transposons, Tn4451 (pIP401) and Tn4452 (pJIR27), were closely related and did not contain large inverted or directly repeated sequences. These transposons represent the first transposable elements from the clostridia to be identified and characterized. PMID- 2881918 TI - Identification and characterization of the Rhizobium meliloti ntrC gene: R. meliloti has separate regulatory pathways for activation of nitrogen fixation genes in free-living and symbiotic cells. AB - We show here that Rhizobium meliloti, the nitrogen-fixing endosymbiont of alfalfa (Medicago sativa), has a regulatory gene that is structurally homologous to previously characterized ntrC genes in enteric bacteria. DNA sequence analysis showed that R. meliloti ntrC is homologous to previously sequenced ntrC genes from Klebsiella pneumoniae and Bradyrhizobium sp. (Parasponia) and that an ntrB like gene is situated directly upstream from R. meliloti ntrC. Similar to its counterparts in K. pneumoniae and Escherichia coli, R. meliloti ntrC is expressed when the cells are grown in nitrogen-limiting media. In addition, R. meliloti ntrC is required for growth on media containing nitrate as the sole nitrogen source and for the ex planta transcription of several R. meliloti nif genes. On the other hand, root nodules elicited by R. meliloti ntrC mutants fix nitrogen as well as nodules elicited by wild-type R. meliloti. These latter results indicate that R. meliloti has separate regulatory pathways for activating nif gene expression ex planta and during symbiotic nitrogen fixation. PMID- 2881921 TI - Strain and species identification by restriction fragment length polymorphisms in the ribosomal DNA repeat of Candida species. AB - Restriction fragment length polymorphisms in the ribosomal DNA (rDNA) have been shown to be a useful criterion for distinguishing among various isolates of Candida albicans. In a sample of 12 clinical isolates, we found six different classes based on variations in the fragments produced from genomic DNA by EcoRI and visualized after Southern transfer by being probed with a plasmid containing Saccharomyces cerevisiae rDNA. Some of the classes appeared to be heterozygous at the rDNA locus. Similar digestion of other Candida species showed that each could be identified on the basis of its restriction patterns. Since these are highly reiterated genes, the differences were apparent on ethidium bromide-stained gels; Southern transfers were not necessary. EcoRI restriction maps of the rDNA of C. albicans, C. stellatoidea, C. tropicalis, and C. guilliermondii were determined. PMID- 2881920 TI - Ammonium and methylammonium transport in Rhodobacter sphaeroides. AB - Rhodobacter sphaeroides maintained intracellular ammonium pools of 1.1 to 2.6 mM during growth in several fixed nitrogen sources as well as during diazotrophic growth. Addition of 0.15 mM NH4+ to washed, nitrogen-free cell suspensions was followed by linear uptake of NH4+ from the medium and transient formation of intracellular pools of 0.9 to 1.5 mM NH4+. Transport of NH4+ was shown to be independent of assimilation by glutamine synthetase because intracellular pools of over 1 mM represented NH4+ concentration gradients of at least 100-fold across the cytoplasmic membrane. Ammonium pools of over 1 mM were also found in non growing cell suspensions in nitrogen-free medium after glutamine synthetase was inhibited with methionine sulfoximine. In NH4+-free cell suspensions, methylammonium (14CH3NH3+) was taken up rapidly, and intracellular concentrations of 0.4 to 0.5 mM were maintained. The 14CH3NH3+ pool was not affected by methionine sulfoximine. Unlike NH4+ uptake, 14CH3NH3+ uptake in nitrogen-free cell suspensions was repressed by growth in NH4+. These results suggest that R. sphaeroides may produce an NH4+-specific transport system in addition to the NH4+/14CH3NH3+ transporter. This second transporter is able to produce normal size NH4+ pools but has very little affinity for 14CH3NH3+ and is not repressed by growth in high concentrations of NH4+. PMID- 2881922 TI - Cloning and expression of a type 1 fimbrial subunit of Actinomyces viscosus T14V. AB - The type 1 fimbriae of Actinomyces viscosus mediate the adherence of this organism to saliva-treated hydroxyapatite. The gene encoding a putative subunit of this fimbrial adhesin was cloned in Escherichia coli, and its product was examined. A. viscosus T14V chromosomal DNA was partially restricted with Sau3AI and cloned into E. coli JM109 by using the plasmid vector pUC13. Two clones, each containing a different DNA insert with a common 4.1-kilobase region, reacted in colony immunoassays with specific polyclonal as well as monoclonal antibodies directed against A. viscosus T14V type 1 fimbriae. Western blot analysis revealed the expression of a 65-kilodalton protein that migrated slightly behind an antigenically similar protein from native type 1 fimbriae. Deletion analysis showed that the gene encoding the cloned protein was localized on a 1.9-kilobase PstI-BamHI fragment and that transcription was dependent on the lac promoter of the vector. The cloned fimbrial protein was purified from the E. coli cytoplasmic fraction by ion-exchange, immunoaffinity, and gel permeation chromatography. Rabbit antibodies prepared against the cloned protein and against purified A. viscosus type 1 fimbriae gave similar patterns with partially dissociated type 1 fimbriae after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. The data therefore provide evidence that the gene cloned encodes a subunit of this fimbrial adhesin. PMID- 2881923 TI - Serum neuroleptic levels, prolactin levels, and relapse: a two-year study of schizophrenic outpatients. AB - For 2 years serum neuroleptic levels, prolactin levels, and clinical states were assessed in 105 male schizophrenic outpatients every 6 months. The patients were taking a variety of neuroleptics at clinically determined fixed doses. Those who had psychotic symptoms at 50% or more of their visits attained serum levels of neuroleptics and prolactin well within or above the range observed in the remitted patients. Neuroleptic and prolactin levels did not discriminate patients who relapsed from those who did not relapse. In the remitted patients who relapsed at least once during the study period, neuroleptic and prolactin serum levels were lower before the relapse episodes than before the stable periods. PMID- 2881925 TI - The glycophospholipid anchor of Thy-1. Biosynthetic labeling experiments with wild-type and class E Thy-1 negative lymphomas. AB - The Thy-1 antigen of the surface of lymphocytes and neurons is anchored to the plasma membrane via a glycophospholipid moiety. In contrast, the Thy-1 synthesized by the class E Thy-1 negative mutant lymphoma is secreted as a hydrophilic species. The present investigation uses the approach of biosynthetic labeling to investigate further the structure of the intracellular Thy-1 of wild type cells and the secreted Thy-1 of these mutant cells. In the wild-type cells, Thy-1 can be labeled with [3H] mannose, [3H]galactose, [3H]fucose, [3H]ethanolamine, and [3H]palmitic acid. In the latter two cases the label is recovered almost exclusively in a detergent-binding Pronase fragment of the protein. The incorporated label is in the form of [3H]ethanolamine, or [3H]palmitate and stearate, respectively. Reductive methylation of biosynthetically labeled Thy-1 and a nonradioactive sample of Thy-1 shows that [3H]ethanolamine is incorporated equally into two residues of ethanolamine, only one of which has a free amino group. A single residue of glucosamine with a free amino group is also detected. Each of the sugar precursors is incorporated with extensive conservation of chemical identity. In the class E cells, each of the labeled sugars but neither [3H]ethanolamine nor [3H]palmitate is incorporated into Thy-1. The anchor moiety therefore appears to be entirely missing, although N-linked oligosaccharide processing is essentially normal. We postulate that the anchor deficiency in the mutant cells results from a biosynthetic lesion. PMID- 2881924 TI - Location of a dicyclohexylcarbodiimide-reactive glutamate residue in the Neurospora crassa plasma membrane H+-ATPase. AB - The proton pump (H+-ATPase) found in the plasma membrane of the fungus Neurospora crassa is inactivated by dicyclohexylcarbodiimide (DCCD). Kinetic and labeling experiments have suggested that inactivation at 0 degrees C results from the covalent attachment of DCCD to a single site in the Mr = 100,000 catalytic subunit (Sussman, M. R., and Slayman, C. W. (1983) J. Biol. Chem. 258, 1839 1843). In the present study, when [14C]DCCD-labeled enzyme was treated with the cleavage reagent, N-bromosuccinimide, a single major radioactive peptide fragment migrating at about Mr = 5,300 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis was produced. The fragment was coupled to glass beads and partially sequenced by automated solid-phase Edman degradation at the amino terminus and at an internal tryptic cleavage site. By comparison to the DNA derived amino acid sequence for the entire Mr = 100,000 polypeptide (Hager, K., and Slayman, C. W. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 7693-7697), the fragment has been identified as arising by cleavage at tyrosine 100 and tryptophan 141. Covalently incorporated [14C]DCCD was released at a position corresponding to glutamate 129. The DCCD-reactive glutamate is located in the middle of the first of eight predicted transmembrane sequences. When the sequence surrounding the DCCD site is compared to that surrounding the DCCD-reactive residue of two other proton pumps, the F0F1-ATPase and cytochrome c oxidase, no homology is apparent apart from an abundance of hydrophobic amino acids. PMID- 2881926 TI - Cell-specific processing of preprosomatostatin in cultured neuroendocrine cells. AB - We have previously found that preprosomatostatin is processed accurately to both somatostatin-14 and somatostatin-28 in pituitary gonadotrophs of transgenic mice. The foreign somatostatin peptides have been shown to enter the regulated secretory pathway of these cells. To determine whether accurate preprosomatostatin processing can occur in any neuroendocrine cell, we introduced preprosomatostatin cDNA expression vectors into several different neuroendocrine cell lines. We found that prosomatostatin was cleaved efficiently to somatostatin 14 and somatostatin-28 in RIN 5F and AtT20 cells, but not in GH4 or PC12 cells. The ability of a particular cell type to process prosomatostatin did not correlate with cellular storage capacity and was independent of the level of biosynthesis of the precursor. These data suggest that prosomatostatin processing requires specific pathways which are present in some neuroendocrine cells, but not in others. PMID- 2881927 TI - The biosynthesis of tabtoxinine-beta-lactam. Use of specifically 13C-labeled glucose and 13C NMR spectroscopy to identify its biosynthetic precursors. AB - Tabtoxinine-beta-lactam, an irreversible inhibitor of glutamine synthetase is produced by several pathovars of Pseudomonas syringae. We have examined tabtoxinine-beta-lactam biosynthesis, an important and poorly characterized step in pathogenesis caused by this organism. We have identified the biosynthetic precursors of tabtoxinine-beta-lactam by incorporating 13C from specifically 13C labeled D-glucose precursors and determining the labeling pattern using 13C NMR spectroscopy. Tabtoxinine-beta-lactam is generated by combining a 4-carbon fragment, a 2-carbon fragment, and a single carbon. The 4-carbon fragment arises from aspartic acid, and the 2-carbon unit is donated from carbons 2 and 3 of pyruvate. The 6-carbon backbone of tabtoxinine-beta-lactam arises from the condensation of fragments from aspartate and pyruvate, probably using reactions analogous to the initial steps in the pathway of lysine biosynthesis. PMID- 2881928 TI - P1-(5'-adenosyl)-P2-N-(2-mercaptoethyl)diphosphoramidate. An affinity reagent for demonstrating the presence of Tyr-beta 311 at the hydrolytic site of F1-ATPase. AB - The compound P1-(5'-adenosyl)-P2-N-(2-mercaptoethyl)diphosphoramidate (AMEDA) was synthesized as an ATP analogue for in situ reaction with the 4-nitro-2,1,3 [14C]benzoxadiazolyl group (NBD) in the labeled F1-ATPase (F1). AMEDA was found to reactivate O-[14C]NBD-F1 via a dual-path mechanism. The principal path involves the binding of AMEDA at a site in F1 with Kd = 14.5 microM and subsequent reaction with the [14C]NBD label. The second slower path involves the direct biomolecular reaction of AMEDA with the radioactive label on F1. The rate of reactivation of O-[14C]NBD-F1 by AMEDA was decreased by ADP or ATP which competes with the ATP analogue for binding to the labeled enzyme. The reaction product was found to contain one adenine group, two phosphate groups, and one [14C]NBD label per molecule as expected from the structure of the compound AMEDA [14C]NBD. Purified AMEDA-[14C]NBD was found to bind to unlabeled F1 with Kd = 2 microM. These observations demonstrate the in situ reaction of bound AMEDA with the nearby [14C]NBD label attached to Tyr-beta 311 and support the assumed presence of Tyr-beta 311 near the phosphate groups of ATP bound at the hydrolytic site of F1-ATPase. The possible locations of Tyr-beta 364, His-beta 427, and Tyr beta 345 relative to Tyr-beta 311 in F1 are discussed, and the validity of the previously proposed model for F1-ATPase with one hydrolytic site assisted by two auxiliary sites is examined and compared with that of the widely accepted alternating sites model. PMID- 2881929 TI - Inositol 1,4,5-trisphosphate releases Ca2+ from vacuolar membrane vesicles of oat roots. AB - In plant cells, transient changes in cytoplasmic Ca2+ levels can modulate numerous developmental processes. Ca2+ is accumulated in the vacuole via a H+/Ca2+ antiport system that is energized by the tonoplast H+-pumping ATPase. Inositol 1,4,5-triphosphate (InsP3), but not inositol 1,4-bisphosphate, myo inositol 1-phosphate, or fructose 2,6-bisphosphate, caused a transient reduction of Ca2+ levels in tonoplast vesicles. The decrease was dependent on InsP3 concentration (Km apparent = 0.6 microM). The InsP3-induced Ca2+ release was blocked by the Ca2+ antagonist, 8-(N,N-diethylamino)-octyl 3,4,5 trimethoxybenzoate-HCl. These results suggest that the vacuolar membrane is one target site for InsP3 action and that InsP3 may operate as a second messenger in the mobilization of intracellular Ca2+ in plant cells. PMID- 2881931 TI - Antitoxin in human pertussis immune globulins. AB - The level of antitoxin i.e. neutralizing antibodies to pertussis toxin, or lymphocytosis promoting factor, was determined in six pertussis immune globulin preparations from different manufactures. A comparison with antitoxin levels after natural pertussis disease in adults showed that pertussis immune globulins did not contain more antitoxin than convalescent phase sera, i.e. they had very low antitoxin content for specific immune globulins. Agglutinin and anti-FHA titres were relatively higher in immune globulins, probably reflecting a difference between the antibody response elicited by whole cell vaccines used for hyperimmunization in immune globulin production and by natural disease. The low antitoxin content of currently available pertussis immune globulin preparations could explain the inefficacy or conflicting results obtained with these products in prophylaxis and therapy of whooping cough. PMID- 2881930 TI - Removal of lipopolysaccharide from acellular Bordetella pertussis vaccine by detergent treatment. AB - Protective antigen was extracted from Bordetella pertussis cells with 1.0 M NaCl and precipitated with ammonium sulfate, 20-40% saturation (designated fraction 15A-1B). The protective antigen was purified further by detergent (Emulphogene BC720) treatment and adsorption to aluminum hydroxide gel (designated fraction 15A-108A). Compared with B. pertussis vaccine and fraction 15A-1B, fraction 15A 108A retained protective activity as assessed by the mouse protection test, but had reduced protein and markedly reduced endotoxin content. Fraction 15A-108A also had reduced leukocytosis-promoting, histamine sensitizing splenomegaly inducing, and adjuvant activities. Emulphogene treatment provided a relatively simple method for removing endotoxin from a potential acellular B. pertussis vaccine. PMID- 2881932 TI - The detoxification of Bordetella pertussis with glutaraldehyde. AB - To improve the whole-cell pertussis vaccine we have studied the inactivation of the biological properties characteristic of Bordetella pertussis phase I bacteria, i.e. histamine-sensitizing, lymphocytosis-promoting and mouse protective activities, by treating a concentrated bacterial suspension with various concentrations of glutaraldehyde. Under the experimental conditions, treatment with 10 mM glutaraldehyde at 37 degrees C for 30 min resulted in a marked reduction of the toxic activities without grossly diminishing the protective potency. Further tests were performed on the stability of the protective potency, on the agglutinin production in mice, and on the freedom from abnormal toxicity in guinea-pigs. PMID- 2881933 TI - Chromosomal abnormalities in adult T-cell leukemia/lymphoma (ATL). A report of six cases with review of the literature. AB - Chromosomal studies were performed on six patients with adult T-cell leukemia (ATL). Structural abnormalities of chromosome 3 were the most common. In one case a complete loss of the short arm of chromosome 10 (10 p-) was noted while in another case a balanced translocation involving chromosome 10p and 4q was found. These abnormalities have not been previously reported. After reviewing the literature, it was concluded that chromosomes 3, 6, 10, 13, 14, and X were most frequently involved in abnormalities. Specific and consistent chromosomal abnormalities were noted in each study. Therefore, it is hypothesised that the mutation rate for this virus may be higher than first expected. Furthermore, the relative consistency of heterogeneous findings in different localities may reflect a geographic clustering of specific chromosomal abnormalities which may in turn be related to specific and geographically associated viral mutations. To support these suggestions not only are more cytogenetic data required but a molecular evaluation of these patients must be carried out to establish a relationship, if any, between genetic abnormalities and the epidemiology of ATL. PMID- 2881934 TI - 100-kD coated vesicle proteins: molecular heterogeneity and intracellular distribution studied with monoclonal antibodies. AB - Proteins with molecular weights of around 100,000 (designated 100K) are found in all coated vesicles. Five monoclonal antibodies have been raised against the major 100K proteins of bovine brain coated vesicles, which migrate on SDS gels as three closely spaced bands. One antibody stains the middle band (band B), two stain both upper and lower bands (bands A and C), and two stain the lower band (band C) only. Thus, the polypeptides in bands A and C are related (but not identical), a result confirmed by NH2-terminal sequencing. Other tissues were found to express proteins corresponding to, and co-migrating with, bands B and C but not band A. Only the two antibodies that recognize both A and C stained fixed and permeabilized tissue culture cells; they both showed a punctate pattern in the plane of the plasma membrane. Double labeling with anti-clathrin antibodies confirmed that the dots correspond to coated pits and vesicles. However, perinuclear staining seen with anti-clathrin, corresponding to Golgi-derived coated vesicles, was conspicuously absent with the two monoclonal antibodies. Affinity-purified polyclonal antisera against the 100K proteins, reported earlier, gave perinuclear as well as punctate staining; these included one antiserum which gave mainly perinuclear staining (Robinson, M. S., and B. M. F. Pearse, 1986, J. Cell Biol., 102:48-54). Thus, different 100K proteins appear to be found in different membrane compartments. Since the 100K proteins are thought to lie between clathrin and the membrane proteins of the vesicle, these results may help to explain how different membrane proteins can be sorted into coated vesicles in different parts of the cell. PMID- 2881935 TI - Management of patients after myocardial infarction. PMID- 2881936 TI - High-performance liquid chromatographic assay for azatadine in human urine. AB - A high-performance liquid chromatographic assay for the quantitative determination of azatadine and a base (1 M sodium hydroxide) hydrolyzable conjugate of azatadine in human urine has been developed. Reversed-phase separation of azatadine and the internal standard, 8-chloroazatadine, was accomplished on a 300 X 3.9 mm I.D. mu Bondapak CN column. Following liquid liquid extraction from urine, azatadine was quantitatively determined by UV detection at 214 nm. No interferences were observed in the extracts obtained from drug-free urine. Detector response (peak area ratio) was linear from 10 to 2500 ng/ml. This method has been shown to provide accurate and precise determinations of the unchanged and hydrolyzed drug in human urine, following the twice daily oral administration (1-2 mg) of azatadine maleate. PMID- 2881937 TI - Simple and sensitive high-performance liquid chromatographic assay for 5 aminosalicylic acid and acetyl-5-aminosalicylic acid in serum. PMID- 2881938 TI - High-performance liquid chromatographic method for the determination of carvedilol and its desmethyl metabolite in body fluids. PMID- 2881939 TI - Highly sensitive determination of 2-hydroxy-N-(3-[m-(1-piperidinylmethyl) phenoxy]propyl)acetamide (desacetyl TZU-0460) in rat plasma by high-performance liquid chromatography. PMID- 2881940 TI - Detection of dengue virus RNA using nucleic acid hybridization. AB - Conditions for using slot-blot nucleic acid hybridization to quantitatively detect dengue-2 virus using a radiolabelled cDNA probe, pVV17, were determined. As little as 11 plaque-forming units of virus were detected using a hybridization mixture without formamide and performing the test at 70 degrees C. While predominantly serotype-specific using stringent (65 degrees C) washing conditions, the probe detected all four dengue virus serotypes using astringent (28 degrees C) washing conditions. No significant qualitative differences were detected using Thai dengue-2 viruses isolated over a 10-year period. High titered, anti-flavivirus antibodies blocked virus detection by an antigen capture, enzyme-linked, immunosorbent assay or by intrathoracic inoculation of Toxorhyncites mosquitoes, but not by nucleic acid hybridization. The appearance of virus-specified RNA coincided with the detection of antigen in infected C6/36 (Aedes albopictus) cells by immunofluorescence, or in cell culture supernatants by the antigen capture method. The method has potential as a diagnostic tool for identifying dengue viruses in clinical and field specimens. PMID- 2881941 TI - Predictors of tardive dyskinesia: results of a cross-sectional study in an outpatient population. AB - A cross-sectional study was conducted to identify predictors of tardive dyskinesia (TD) in a group of 180 psychiatric outpatients maintained on neuroleptic medications. The estimated prevalence of this involuntary movement disorder was 33% in the total study population. Using multiple logistic regression, we found that TD was independently related to five factors: being 55 yr of age and older; being male; using depot (injectable) neuroleptics; having 6 or more years of neuroleptic exposure; and having less than 6 months of psychiatric hospitalization. In addition, the effect of depot medication was much greater in white males than it was in other race-sex groups. We observed no other interaction effects between pairs of predictor variables, nor did we find significant independent effects of race, denture use, DSM III diagnosis, current neuroleptic dose and potency, percent time on neuroleptics, and recent use of antiparkinsonian drugs or lithium. This study is serving as a pilot investigation for a large prospective incidence study that has already begun among patients at risk of developing TD in the same source population. PMID- 2881942 TI - In vivo regulation of non-insulin-mediated and insulin-mediated glucose uptake by epinephrine. AB - In vivo glucose uptake (Rd) occurs via two mechanisms: 1) insulin-mediated glucose uptake (IMGU), which occurs in insulin-sensitive tissues, and 2) noninsulin-mediated glucose uptake (NIMGU), which occurs in both insulin sensitive and insulin-insensitive tissues. Thus, in the postabsorptive (basal) state Rd = IMGU + NIMGU. To determine whether these two pathways for in vivo glucose disposal are regulated independently, we studied the effect of stress levels of epinephrine (EPI) on IMGU and NIMGU in seven normal men after an overnight fast. To study NIMGU, somatostatin (600 micrograms/hr) was infused to suppress endogenous insulin secretion, and glucose turnover was measured isotopically while the serum glucose level was clamped at about 200 mg/dL for 240 min. Separate studies were done during the infusion of saline or EPI (0.2 microgram/kg X min). The final 120 min of each study were used for data analysis. Under these conditions insulin action is absent and Rd = NIMGU. NIMGU was 210 +/- 15 (+/- SEM) and 200 +/- 17 mg/min during saline and EPI treatment, respectively (P = NS). Therefore, EPI has no ability to modulate NIMGU. To measure the effect of EPI on Rd, hyperglycemic (200 mg/dL) hyperinsulinemic clamp (30 mU/M2 X min) studies were performed during the infusion of saline and EPI. EPI decreased Rd by 46 +/- 6% (751 +/- 85 to 405 +/- 43 mg/min; P less than 0.01). When the effect of EPI on IMGU (Rd - NIMGU) was considered separately, the inhibitory effect of EPI was more potent, as indicated by a 61 +/- 12% decrease in IMGU. In conclusion, 1) EPI inhibits IMGU, but has no effect on NIMGU; 2) when NIMGU is taken into account, EPI has a more potent ability to inhibit IMGU than previously found; and 3) the systems responsible for NIMGU and IMGU are independently regulated. PMID- 2881943 TI - Hyperglucagonemia increases resting metabolic rate in man during insulin deficiency. AB - The physiological significance of the hyperglucagonemia that occurs in patients with many catabolic conditions is unclear. The effect of hyperglucagonemia on resting metabolic rate (RMR) was studied in six normal subjects. Infusion of somatostatin (SRIH; 500 micrograms/h for 210 min) resulted in a 5-fold decrease in plasma C-peptide and a 2-fold decrease in plasma insulin and glucagon concentrations, but did not change RMR significantly. When glucagon (0.2 micrograms/kg X h), was infused with SRIH (500 micrograms/h for 210 min), the decreases in plasma C-peptide and insulin were similar to that during the infusion of SRIH alone, but plasma glucagon increased from 160 +/- 24 (+/- SEM) to 560 +/- 80 pg/mL (P less than 0.001). There was a significant increase in RMR during the entire period (210 min) of glucagon infusion (P less than 0.01). During the last hour of the glucagon plus SRIH infusion, the RMR was 1.38 +/- 0.10 Cal/min, which was 15% higher than the preinfusion RMR (1.19 +/- 0.10 Cal/min; P less than 0.01) and 14% higher than the RMR during the same period when SRIH alone was infused (1.21 +/- 0.11 Cal/min; P less than 0.01). When SRIH and glucagon were infused, protein oxidation (calculated from urinary nitrogen loss) was 52 +/- 5 mg/min, 29% higher than when SRIH alone was infused (40 +/- 5 mg/min; P less than 0.05). These results indicate that hyperglucagonemia during insulin deficiency results in an increase in energy expenditure, which may contribute to the catabolic state in many conditions. PMID- 2881944 TI - Renal response to intravenous somatostatin in insulin-dependent diabetic patients and normal subjects. AB - The acute effects of iv somatostatin (SRIH; 100 micrograms/h) on the urinary flow (Uvol), effective renal plasma flow (RPF), and glomerular filtration rate (GFR) were compared with those of a control infusion of 0.15 M NaCl in nine insulin dependent diabetic (IDD) patients of less than 10 yr disease duration and six normal subjects (NS). RPF and GFR were measured using a standard primed constant isotope infusion of [125I]iodohippurate and [51Cr]chromium EDTA. Uvol, RPF, and GFR were measured during 20-min clearance periods. During the NaCl infusion mean Uvol, RPF, and GFR were 14.1 +/- 0.2 (+/- SEM), 708 +/- 4, and 150 +/- 1 mL/min in the IDD group and 12.7 +/- 0.4, 568 +/- 5, and 110 +/- 2 mL/min in the NS group, respectively. In the IDD patients Uvol, RPF, and GFR decreased from 16.6 +/- 1.8, 670 +/- 30, 146 +/- 4 mL/min pre-SRIH to 9.2 +/- 1 (P less than 0.001), 553 +/- 25 (P less than 0.001), and 130 +/- 5 (P less than 0.001) mL/min, respectively, at 120 min during the SRIH infusion. Similarly, in the NS group mean Uvol, RPF, and GFR were 14.2 +/- 0.6, 552 +/- 15, and 112 +/- 5 mL/min pre SRIH and decreased to 7.4 +/- 0.6 (P less than 0.001), 422 +/- 7 (P less than 0.001), and 93 +/- 3 (P less than 0.001) mL/min, respectively, after 120 min of the SRIH infusion. SRIH, therefore, had a profound effect on renal function in both IDD patients and NS, resulting in a reduction in RPF, GFR, and, as a consequence, Uvol. PMID- 2881945 TI - Inhibition of memory in the chick using a monoclonal anti-Thy-1 antibody. AB - One-day-old chicks trained on a single trial passive avoidance task were administered a monoclonal anti-chick Thy-1 antibody, either intracranially or subcutaneously, at various times before and after learning and retention tested at various times post-learning. This procedure resulted in profound amnesia when anti-Thy-1 antibody was administered immediately before learning (5 min) in the case of the subcutaneous injections or 5 min before until 5 min after the learning process with intracranial injections. Antibody administered at other times, either before or after learning had little or no effect on retention. Retention levels were normal until 50 min post-learning, then declined sharply and remained at control levels for the duration of the test period. Chicks injected with anti-chick cerebellum or anti-rat Thy-1 antibodies showed no evidence of amnesia for the concentration of the antibodies used. PMID- 2881946 TI - Loop transplant. PMID- 2881947 TI - Molecular cloning of a polymorphic DNA endonuclease fragment associates insulin dependent diabetes mellitus with HLA-DQ. AB - A BamHI 3.7-kilobase (kb) fragment detected by an HLA-DQ beta-chain complementary DNA (cDNA) probe and negatively associated with insulin-dependent diabetes mellitus (IDDM) was cloned and sequenced to localize the polymorphism to BamHI sites in intervening sequences of an HLA-DQ beta-chain gene. A probe of the first intervening sequence (IVS 1) showed the BamHI 3.7-kb fragment in 6 of 17 HLA DR3/4 controls but in 0 of 13 DR-identical IDDM patients. All IDDM patients (13 of 13) had BamHI fragments of 12 and 4 kb, detected in 9 of 17 controls (P less than 0.02). The simple restriction fragment length polymorphism pattern of the IVS 1 probe was exploited by comparing 113 IDDM patients with 177 healthy controls to show increased prevalences in IDDM of the 12-kb (P less than 0.0001) and 4-kb (P less than 0.0001) fragments. In IDDM patients younger than 20 yr at onset, 98% were 12- and/or 4-kb positive, compared with 63% of controls (P less than 0.0001), giving a relative risk of 91.8 for individuals with both fragments. The 12-kb fragment was linked to HLA-DR4, and the 4-kb fragment to HLA-DR3. Both serologic markers were split and a non-DR3/non-DR4 IDDM patient was 4-kb positive. HLA-DQ seems therefore closer, than HLA-DR, to an IDDM susceptibility gene. PMID- 2881948 TI - Vagal regulation of insulin, glucagon, and somatostatin secretion in vitro in the rat. AB - Using a new in vitro procedure of the isolated perfused rat pancreas with vagal innervation, electrical vagal stimulation produced an increase in both insulin and glucagon secretion in proportion to the pulse frequency, but an inhibition in somatostatin release. When atropine was infused, both insulin and glucagon responses to vagal stimulation were partially suppressed, whereas somatostatin release was enhanced. In the presence of hexamethonium, vagal stimulation failed to affect insulin, glucagon, or somatostatin secretion. Propranolol partially blocked both insulin and glucagon responses but did not influence somatostatin response. Phentolamine had no significant effect on release of hormones. Simultaneous administration of propranolol and phentolamine tended to inhibit both insulin and glucagon responses to vagal stimulation. These findings suggest that not only a cholinergic but also a noncholinergic neuron may be involved in vagal regulation of pancreatic hormone secretion and that these neurons may be under the control of preganglionic vagal fibers via nicotinic receptors. PMID- 2881951 TI - Distribution of tyrosine-hydroxylase (TH)-immunoreactive neurons in the diencephalon of the pigeon (Columba livia domestica). AB - The distribution of tyrosine-hydroxylase (TH)-immunoreactive cell bodies and fibers in the diencephalon has been investigated with immunohistological techniques in the pigeon. The results suggest that TH is present in a number of morphologically distinct neuronal systems. Preoptic and hypothalamic TH neurons were subdivided into a medial periventricular and a lateral group. The medial group starts with a rostral collection of small cells in the preoptic region. A significantly larger collection of TH neurons occupies the paraventricular nucleus (PVN) (stratum cellulare internum) and mainly consists of large multipolar cells. Further caudally, the main concentration of cells is in the hypothalamic posteromedial and the periventricular regions of the tuberoinfundibular (arcuate) nucleus. No TH neuron was found in the ventral and lateral parts of the tuberoinfundibular region, suggesting that the prominent tuberoinfundibular dopaminergic system described in mammals is absent in the pigeon. This further substantiated by the relative scarcity of TH immunoreactive fibers and varicosities in the neurohemal zone of the median eminence (ME). The caudalmost components of the medial group appear to be continuous with the large population of TH neurons distributed in the midline of the mesencephalon. Tyrosine-hydroxylase-immunopositive cells have not been found in the paraventricular organ. The lateral group consists of TH neurons loosely arranged in the lateral hypothalamus, including regions of the supraoptic nucleus and hypothalamic posterolateral nucleus. Tyrosine-hydroxylase containing neurons vary widely in size, shape, and dendritic arborization in each diencephalic region. However, it is possible to distinguish two main cell types. Small bipolar neurons with two simple arborizing dendrites were concentrated in the medial periventricular system. The second type of cell is large, multipolar with four to five branching dendrites. This latter cell type occurs mainly in the lateral system and in the PVN. Major fiber bundles containing TH immunoreactivity were identified in the lateral and periventricular hypothalamus. The paraventricular organ and the organum vasculosum laminae terminalis contained the densest arborization of fibers and varicosities. In the ME, dense innervation was found in the subependymal layer. Dense arborizations of TH positive fibers and varicosities were located in the septal nuclei and the paleostriatum augmentatum. PMID- 2881950 TI - Age related variations of serum concentrations of normally occurring IgG antibodies to Clostridium perfringens. AB - In studies using indirect immunofluorescence IgG antibodies to Clostridium perfringens were found in sera from healthy adults. Sera from 236 healthy children were examined. The normally occurring IgG antibodies to C perfringens were found to have an age related variation. Preliminary data suggest that they are not correlated to C perfringens alpha toxin. The antigen(s) against which the antibodies are directed is/are probably part of the cell wall, but its/their exact nature is not known. PMID- 2881949 TI - Hemophilia B (Christmas disease) variants and carrier detection analyzed by DNA probes. AB - We have used two strategies to study 14 hemophilia B families from 11 kindreds for possible carrier detection and prenatal diagnosis. First, we sequentially used the Factor IX probes (sequentially with restriction enzymes Taq I, Xmn I, and Dde I), and the linked probes p45h (Taq I), p45d (Pst I), and 52a (Taq I) for restriction fragment length polymorphism (RFLP) analysis. Second, we searched for useful variant Taq I digestion fragments using the Factor IX complementary DNA. Two separate new Taq I variants in exon VIII were identified. Using both strategies, 11 of 14 families (from 9 of 11 kindreds) were informative for further studies. In five kindreds studied in detail, the carrier status of all 11 at risk females was determined and prenatal diagnosis could be offered to the offsprings of each of the six carriers identified. Thus, in this study, we have identified a higher proportion of informative families than has previously been reported. PMID- 2881952 TI - Linear cutaneous neuromas (dermatoneurie en stries): a limited phakomatosis with striated pigmentation corresponding to cutaneous hyperneury (featuring multiple endocrine neoplasia syndrome?). AB - A 60-year-old woman developed a progressive linear pigmentation on the trunk. Skin biopsy demonstrated an increase in the number and size of neural fibers in the dermis. Clinical and paraclinical investigations of this unusual disease showed findings similar to the hereditary type of Sipple syndrome (multiple endocrine neoplasia syndrome, Type 2b). Such findings as Marfanoid habitus, abnormal electromyography and hypertrophy of the corneal nerves suggest that our patient's disease and Sipple syndrome are identical. However, such other symptoms of Sipple syndrome as presence of endocrine tumors are absent. Questions of long term prognosis and physiopathogenicity are raised, since no nerve growth factor was detected in this patient. The name of linear cutaneous neuromas is suggested for the patient's lesions, and a possible association with the pigmentation and cutaneous neuromas of the MEN 2b syndrome. PMID- 2881953 TI - Surface densities of murine Ia+ dendritic epidermal cells (Ia+DECs) and Thy-1+ dendritic epidermal cells (Thy-1+DECs) in relationship to aging and ultraviolet B (UVB) radiation. PMID- 2881954 TI - Properties of partially purified mouse epidermal transglutaminase. PMID- 2881955 TI - A comparative immunohistochemical study of adult T cell leukemia and cutaneous T cell lymphoma. PMID- 2881956 TI - Hemodynamic and hormonal abnormalities in canine aortic coarctation at rest and during exercise. AB - This study was designed to determine the hemodynamic and hormonal consequences of aortic coarctation at rest and during treadmill exercise. Twelve normal adult dogs served as controls. In eight dogs coarctation was created within 1 week of birth by banding the aorta just proximal to the ductus ligament, thereby fixing luminal diameter at 1 to 2 mm. Studies were performed 18 months after operation. Vascular pressures were monitored proximal and distal to the coarctation, cardiac output and regional blood flow were evaluated with radioactive microspheres and blood samples were collected for determination of hormone levels and blood gases. At rest, systolic pressure in the proximal aorta was 130 +/- 12 mm Hg (mean +/- SD) in the control group and 167 +/- 16 mm Hg in dogs with coarctation (p less than 0.01). During exercise at a level that doubled heart rate and cardiac index, mean aortic pressure increased by 11 and 31% (p less than 0.01) in the control and the coarctation group, respectively. Mean distal aortic pressure increased by 8% during exercise in control dogs but decreased by 29% in dogs with coarctation. Exercise decreased flow to the kidneys and the large intestine in the coarctation group. Plasma norepinephrine concentrations were greater in the coarctation group than in control dogs at rest; during exercise, plasma norepinephrine, epinephrine and renin activity increased in both groups, but to a greater degree in the group with coarctation. These results confirm an abnormality in renal and gut perfusion in experimental coarctation and suggest that this may be related to a decline in perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881957 TI - Infections complicating puncture wounds of the foot. AB - Pedal puncture wounds are a relatively common injury seen predominantly during the warm weather months and in children. Although most of these injuries heal completely with no sequelae, up to 10% may become infected and produce late complications. Of these, osteomyelitis caused by P. aeruginosa is the most devastating, and it may progress to bone destruction that will require extensive surgical debridement. If instituted early, adequate primary care usually provides the best chance of prevention of these infections. PMID- 2881958 TI - Effects of long-term medical treatment with cimetidine and bethanechol in patients with esophagitis and Barrett's esophagus. AB - To evaluate long-term medical therapy in patients with Barrett's esophagus, six patients were studied before and after long-term therapy with cimetidine for a mean period of 11.7 months. Some patients also received bethanechol. All had severe symptoms of gastroesophageal reflux resistant to intensive antacid therapy, specialized columnar epithelium by biopsy, and endoscopic evidence of severe inflammation. Esophageal manometry documented a hypotensive lower esophageal sphincter in three patients and low peristaltic amplitude in the distal esophagus in four. Treatment was begun with cimetidine, 300 mg orally four times daily. If symptoms did not totally abate, bethanechol, 25 mg orally four times daily, was added. Cimetidine completely relieved or dramatically reduced symptoms in all patients. Adding bethanechol produced further symptomatic improvement in three of four patients. After initial dilatation in the two patients with strictures, there was no recurrence. Endoscopic evidence of inflammation resolved completely in four patients and was markedly improved in two. Treatment with both drugs was well tolerated by all patients. The abnormally placed squamo-columnar junction did not regress during follow-up. PMID- 2881959 TI - Coronary artery spasm. Part II. AB - Coronary artery spasm can occur in several settings, often combined with coronary artery disease and thrombosis. Calcium channel blockers and beta-blockers are primary treatment modalities. The role of alpha-blocking agents remains unconfirmed. PMID- 2881960 TI - Pharmacological treatment of panic disorder. AB - Panic disorder has recently been recognized as a distinct sub-type of anxiety which may occur with or without phobic avoidance. Controlled prospective trials have demonstrated the efficacy of the tricyclic antidepressants and monoamine oxidase inhibitors in the treatment of this disorder. The use of benzodiazepines and beta-blockers has been more controversial. Some preliminary studies assessing other pharmacological agents are available. Methodological problems limit the conclusions which may be drawn from available data. PMID- 2881961 TI - Amnesic and anxiolytic effects of intravenous diazepam in dental anxiety. AB - The effects of intravenous administration of diazepam (average 20 mg) on learning, performance and mood were assessed in dental patients. These patients required sedation due to excessive anxiety in a dental situation, or because they were to undergo stressful surgery. On a verbal learning task, subjects recalled and recognized significantly fewer words from a list presented after drug administration than from a list presented prior to drug administration, when tested at the end of the treatment period. When tested after treatment, subjects recognised few of a series of picture postcards that had been presented to them during the course of treatment. Subjects showed no significant impairments after diazepam treatment on digit-symbol substitution, symbol copying or number cancellation tasks compared to pre-treatment scores; however, there was a small but significant reduction in the number of finger-taps made. Mood-rating scales showed significant increases in sedation and well-being after diazepam treatment compared to pre-treatment scores, and also a significant reduction in anxiety levels. This study shows that the amnesic effects of diazepam are present in a "real-life" stress situation. PMID- 2881962 TI - Drug delivery to the brain by central infusion: clinical application in patients with Alzheimer's disease. PMID- 2881963 TI - The use of hypnotics and anxiolytics in the elderly. AB - Anxiety and insomnia are prevalent conditions in the elderly, and anxiolytics and hypnotic drugs are commonly used. Pharmacokinetic variables--absorption, distribution, metabolism and elimination--are all altered to a greater or lesser extent. As a general rule, the elderly are more sensitive to psychotropic drug actions than younger patients. This is particularly so in the over 80s. The elderly tend to suffer from physical conditions which may cause insomnia and anxiety, and medication for those physical complaints may interact with psychotropic medication. In the treatment of insomnia, short- or intermediate acting benzodiazepines are preferable to long-acting compounds which tend to accumulate and produce confusional states and ataxia. Similarly, the benefit/risk ratio for anxiolytics is least in the elderly. Compounds of intermediate half life and no active metabolites, such as oxazepam, are preferable. Anxiety syndromes occurring in other contexts, e.g. dementia may be better treated with low doses of antipsychotic drugs. PMID- 2881965 TI - Depot antipsychotics in practice. Their role in schizophrenia and related psychoses. PMID- 2881964 TI - A treatment trial with an analog of thyrotropin-releasing hormone (DN-1417) and des-tyrosine-gamma-endorphin in schizophrenia. AB - Clinical prospects of an analog of thyrotropin-releasing hormone (DN-1417) and des-tyrosine-gamma-endorphin (DT gamma E) in schizophrenia were examined by using the Brief Psychiatric Rating Scale (BPRS) and the electroencephalogram (EEG). Twelve inpatients with chronic schizophrenia were administered fixed doses of neuroleptics throughout the study. Six patients were treated with DN-1417 (DN 1417 group), and the remaining 6 patients with DT gamma E (DY gamma E group). One mg/day of DN-1417 or DT gamma E was given intramuscularly for 2 consecutive weeks followed by 1 week of no drug treatment. In the DN-1417 group, both total BPRS scores and scores on hallucinatory behaviour and unusual thought content decreased in the first and third weeks. The power values of alpha and beta activities from the frontal area increased in the first and third weeks, whereas an increase in alpha activity and a decrease of high-fast beta activity from the occipital area were obtained during the study. On the other hand, the DT gamma E group failed to show either a decrease in BPRS scores or any remarkable EEG changes except for a slight decrease in beta activity. These results suggest that the positive symptoms of schizophrenia are improved by DN-1417 treatment, and that the alterations in BPRS scores coincide with changes in the frontal EEG. PMID- 2881966 TI - Modified responses to recipient and donor B cells by genetically donor T cells from human haploidentical bone marrow chimeras. AB - After administration of haploidentical stem cells to infants with severe combined immunodeficiency disease (SCID), mature T cells of donor karyotype appear later in the recipient without causing graft-vs-host disease (GVHD). To investigate the effect of the host microenvironment on these genetically donor T cells, mixed leukocyte cultures were carried out. Unfractionated mononuclear cells (MNC) from eight infants with SCID immunologically reconstituted by haploidentical bone marrow stem cells responded in the same pattern as MNC from non-chimeric individuals to autologous and allogeneic irradiated MNC, even though they contained all genetically donor T cells and all genetically patient B cells and monocytes. This included surprisingly vigorous proliferative responses of the patients' MNC to the original donors' irradiated MNC. This autoreactivity could be detected as soon as T cell function appeared post-transplantation and appeared to increase with time. It could be blocked by the addition of monoclonal antibodies to HLA Class II antigens. Responses of most patients' MNC were similar whether stimulated by irradiated MNC from the donor or non-donor parent or by those from unrelated normal controls. Purified genetically donor T cells that had matured from stem cells in the patient's microenvironment responded vigorously to purified donor B cells. These same cells responded much less to patient B cells. In six cases, such genetically donor T cells responded less to patient B cells than fresh donor T cells did to donor B cells in the autologous mixed leukocyte response. By contrast, T cells of donor karyotype from three of the patients responded more vigorously to donor B cells than fresh donor T cells did. Thus, genetically donor T lymphocytes that had matured from stem cells in the recipient microenvironment behaved differently from those that had matured in the donor. The hyporesponsiveness of genetically donor T cells from the patient to patient B cells does not appear to be due to T suppressor cells. PMID- 2881967 TI - Deficiency of the C3b/C4b receptor (CR1) of erythrocytes in systemic lupus erythematosus: analysis of the stability of the defect and of a restriction fragment length polymorphism of the CR1 gene. AB - The role of genetic factors in controlling CR1 quantitative expression on erythrocytes (E) of patients with systemic lupus erythematosus (SLE) was reexamined by determining the temporal stability of CR1 numbers and the frequency of a CR1 genomic restriction fragment length polymorphism (RFLP). The mean number of binding sites/(E) for Yz-1 monoclonal anti-CR1 correlated with the number of sites for polyclonal anti-CR1 that had been determined 2 to 4 yr previously in 18 normal persons (p less than 0.001), 18 patients (p less than 0.001), and 28 relatives (p less than 0.001), indicating that CR1 sites/E was a stable characteristic in all three groups. The mean number of Yz-1 sites/E was 281 +/- 34 (+/- SEM) in 28 probands with SLE and 457 +/- 21 in 93 relatives, both determinations being less than that for 100 normal persons, 553 +/- 21 (p less than 0.002). Thirty-six patients and 51 normal individuals were also assessed for the presence of the 7.4 kb and 6.9 kb HindIII CR1 allelic restriction fragments that correlate with high and low expression, respectively, of CR1 on E. The distribution of patients differed from normal (p less than 0.05), with a smaller proportion being homozygous for the 7.4 kb allele. In addition, the mean numbers of Yz-1 sites/E for patients and relatives who were homozygous (p less than 0.02) and heterozygous (p less than 0.05) for the 7.4 kb allele were significantly lower than those for normal persons matched for the HindIII RFLP, suggesting the existence of additional heritable factors that decrease CR1 expression. The stability over time of the CR1 deficiency among patients, the finding of decreased CR1 number among an expanded group of relatives, the altered frequency among patients of CR1 alleles defined by the HindIII RFLP, and the decreased expression of CR1 on E among patients and relatives compared with normal individuals having the same HindIII RFLP indicate a role for genetic factors in CR1 deficiency in SLE. PMID- 2881968 TI - Hemorrhagic fever with renal syndrome: treatment with recombinant alpha interferon. PMID- 2881969 TI - Issues in drug management. Part I. Antidepressants and chronic nonmalignant pain: a review. PMID- 2881970 TI - [Effects of uterine contraction and a beta-stimulant on placental and fetal brain blood flow in correlation with fetal heart rate changes]. AB - The effects of uterine contraction on placental and fetal brain blood flow in correlation with fetal heart rate change and also beta-stimulant on placental and fetal brain blood flow during late deceleration were studied in late pregnant rabbits. We determined the fetal heart rate (FHR) and placental and fetal brain blood flow by a thermocouple method under urethane anesthesia. Fetuses exposed to a more than 30% decrease in placental blood flow by uterine contraction developed more than 20% bradycardia and also a significant decrease in fetal brain blood flow. There are a significant relationship between the decrease in FHR and fetal brain blood flow. beta-stimulant administered to the mother suffering from already severely hypoxic fetal bradycardia increased FHR in accordance with the increase in the placental blood flow and moreover there was recovery from decreased fetal brain blood flow. PMID- 2881971 TI - [A case of multiple endocrine neoplasia (MEN) type IIb]. PMID- 2881972 TI - [Genetic counseling and prenatal diagnosis in Duchenne myopathy: yesterday, today and tomorrow]. AB - The coming of molecular biology has greatly modified the concept of genetic counselling and prenatal diagnosis of Duchenne muscular dystrophy. The most important stages of the genetic counselling are reported: estimate of the risk and carrier detection. This heterozygote detection is now possible in a few cases owing to polymorphic DNA markers recently identified that are genetically linked to the DMD gene locus and detected with probes. An analysis of foetal DNA is also possible and allows us to consider prenatal diagnosis of this affection. This study is yet limited by two impediments: on one hand low rate of informative families, on the other hand use of markers that are not very closely linked to DMD involving recombinations and risks of errors. The solution of these problems is in the use of linked DNA markers with the best polymorphism flanking the Duchenne muscular dystrophy locus. Finally the authors report the necessity of strict collaboration systems between clinical experts, geneticists, biologists and informaticians. PMID- 2881973 TI - Guillain-Barre syndrome and other neurologic syndromes in hepatitis A, B, and non A, non-B. AB - Guillain-Barre syndrome and other neurologic syndromes occur rarely as complications of viral hepatitis, although a causal association has not been established. Seven cases of serologically documented hepatitis A have been reported with Guillain-Barre syndrome; all recovered, with mild neurologic residua in four. Eight cases of serologically documented acute hepatitis B have been reported with Guillain-Barre syndrome; all recovered, with mild neurologic residua in two. In one case, immune complexes of hepatitis B surface antigen and its antibody were present in the cerebrospinal fluid. Other neurologic syndromes have also been reported in patients with serologically defined viral hepatitis, including mononeuritis, auditory neuritis, and seizures. Chronic hepatitis B and mononeuritis multiplex are found together in 31-54% of patients with periarteritis nodosa. The mechanisms for these associations are unknown, but may include direct cytotoxicity of the virus or immune-mediated damage. Vasculitis of the vasa nervorum plays an intermediate role in at least some cases. PMID- 2881974 TI - Neuroleptic malignant syndrome. AB - Neuroleptic Malignant Syndrome is a disabling reaction to neuroleptic drugs recently discussed in psychiatric literature in Europe, Japan, and the United States. It is rare but potentially fatal and is more likely to occur in men, especially young men, than in women. The cause is unknown, but dopamine depletion in the brain is suspected. Treatment usually begins by withdrawing the neuroleptics and then providing supportive therapy for the usual symptoms of high fever, muscular rigidity, labile blood pressure, and tachycardia. The Neuroleptic Malignant Syndrome usually lasts two to three weeks. PMID- 2881975 TI - Personality of panic disorder alcohol abusers. AB - Seventeen (28%) of 61 panic disorder patients in a drug treatment study were retrospectively found to have a history of alcoholism (none had abused alcohol in the past year), More men than women had a history of alcohol abuse (p less than .03). Alcohol patients were less independent and less able to recognize appropriate social cues on personality testing. There was significant improvement in general anxiety for the drug treatment and nonalcoholic placebo group but not for the alcohol placebo group. This indicates a superior response to supportive therapy for general anxiety in the placebo group without an alcohol abuse history compared with the placebo group with an alcohol abuse history. PMID- 2881976 TI - Characterization of binding of 3H-SCH 23390 to dopamine D-1 receptors. Correlation to other D-1 and D-2 measures and effect of selective lesions. AB - The binding of 3H-SCH 23390 to membranes from rat and mouse brain tissue has been investigated. The binding was saturable and reached equilibrium after 60 minutes. Nonspecific binding was low. Association and dissociation rates were Mg++ sensitive. In almost all respects the binding of 3H-SCH 23390 was comparable to the binding of 3H-piflutixol and 3H-cis(Z)-flupentixol. The density of binding sites in striatum was greater than in limbic structures which in turn was greater than in frontal cortex. The density of binding sites in these structures were comparable with those of 3H-piflutixol and 3H-cis(Z)-flupenthixol, 2-3 times higher than the D-2-receptor density. Whereas an increase was seen in 3H-SCH 23390 binding. The binding was decreased approximately 72% 3 weeks after unilateral kainic acid lesion whereas that of 3H-spiperone was only decreased 56%. Finally, the affinities of neuroleptics to the 3H-SCH 23390-binding sites correlated to the affinities to 3H-piflutixol-binding sites and to the effects on DA-sensitive adenylate cyclase. Agonist competition curves were shallow and the data best fit a two-site model composed of a high and a low affinity component. Thus, 3H-SCH 23390 is regarded as a highly selective ligand for brain dopamine D 1 receptors in vitro. PMID- 2881977 TI - Lack of effect of chronic carbamazepine on brain somatostatin in the rat. AB - We investigated the effects of chronic carbamazepine treatment in rats on brain somatostatin. Following 12 days of carbamazepine treatment, no changes in somatostatin levels were found in any of the brain areas examined which included: amygdala, hippocampus, caudate-putamen, median eminence, arcuate nucleus, nucleus accumbens, nucleus interstitialis of the stria terminalis, nucleus periventricularis, parietal cortex, and occipital cortex. Thus, carbamazepine in low doses does not affect basal levels of brain somatostatin in the rat, in contrast to the previous reports of decreased somatostatin in the cerebrospinal fluid of affectively ill patients. PMID- 2881978 TI - Active site chemistry of lysyl oxidase. AB - The bimolecular reduction of the Cu(II)-based enzyme lysyl oxidase with two inorganic reductants, tris bipyridylchromium(II) and (1,3,6,8,10,13,16,19) octaazabicyclo (6,6,6)eicosanecobalt(II) has been examined at various ionic strength and [H+] conditions. The electrochemical properties of the enzyme have also been examined. The results show that Cu(II) is the redox site in the enzyme and has E 1/2 = 0.05 +/- 0.005 V against SCE. The observed rate constants, kobs, for the reduction of the enzyme by either Cr(bpy)32+ or Co(sep)2+ at any concentration of the reductant increased with the ionic strength of the medium. The ionic strength dependence of kobs has been analyzed in terms of the charge of the active site being 1 +. PMID- 2881979 TI - Enhancement of gamma-aminobutyric acid binding by the anxiolytic beta-carbolines ZK 93423 and ZK 91296. AB - The effects of two anxiolytic beta-carboline derivatives, ZK 93423 and ZK 91296, on the binding of gamma-[3H]aminobutyric acid ([3H]GABA) to brain membrane preparations from rat cerebral cortex were examined. ZK 93423 concentration dependently enhanced the specific binding of [3H]GABA, with a maximal increase of 45% above control at a 50 microM concentration. A less pronounced increase was induced by diazepam and by the partial agonist ZK 91296. Scatchard plot analysis revealed that the effect of ZK 93423 was due to an increase in the total number of high- and low-affinity GABA binding sites. The action of ZK 93423 was mediated by benzodiazepine recognition sites since it was blocked by the benzodiazepine antagonists Ro 15-1788 and ZK 93426 at concentrations that failed to modify [3H]GABA binding on their own. Moreover the stimulatory effect of ZK 93423 on [3H]GABA binding was also blocked by the beta-carboline inverse agonist ethyl beta-carboline-3-carboxylate. These results are consistent with the view that ZK 93423 and ZK 91296, similarly to benzodiazepines, exert their pharmacological effects by enhancing the GABAergic transmission at the level of the GABA/benzodiazepine receptor complex. PMID- 2881981 TI - Both short- and long-term effects of nerve growth factor on tyrosine hydroxylase in calf adrenal chromaffin cells are blocked by S-adenosylhomocysteine hydrolase inhibitors. AB - We have previously shown that primary cultures of calf chromaffin cells respond to nerve growth factor (NGF) treatment with a selective induction of tyrosine hydroxylase (TH), which takes 48 h to be manifested. In the present study, we report that short exposure of calf chromaffin cells to NGF (5-60 min) results in TH activation, which involves a change in the Vmax of the enzyme with no change in the number of enzyme molecules, similar to an effect that has been previously reported in PC12 cells. This activation is markedly potentiated when the chromaffin cells are plated on a laminin substrate, such that after 5 min of NGF exposure, there is an approximately fourfold increase in the TH activity. Both short-term activation and long-term TH induction brought about by NGF treatment are blocked by 5'-deoxy-5'-methylthioadenosine and other drugs that act as S adenosylhomocysteine (SAH) hydrolase inhibitors to block methylation by end product inhibition. These drugs did not inhibit cyclic AMP-mediated TH activation or increases in the levels of TH. However, measurements of the degree of blockade of methylation in cells treated with these drugs, taken together with conceptual information regarding the nonregulatory nature of methylation in eukaryotic cells, were not consistent with inhibition of methylation as the crucial effect of the drugs to block the effects of NGF. Nonetheless, since SAH hydrolase inhibitors selectively inhibited NGF-mediated effects, and not comparable effects triggered by other stimuli, these compounds provide useful tools in future studies of the biochemical signalling mechanism of NGF. PMID- 2881980 TI - Tyrosine hydroxylase is activated and phosphorylated on different sites in rat pheochromocytoma PC12 cells treated with phorbol ester and forskolin. AB - Incubation of rat pheochromocytoma PC12 cells with 4 beta-phorbol-12 beta myristate-13 alpha-acetate (PMA), an activator of Ca2+/phospholipid-dependent protein kinase (protein kinase C), or forskolin, an activator of adenylate cyclase, is associated with increased activity and enhanced phosphorylation of tyrosine hydroxylase. Neither the activation nor increased phosphorylation of tyrosine hydroxylase produced by PMA is dependent on extracellular Ca2+. Both activation and phosphorylation of the enzyme by PMA are inhibited by pretreatment of the cells with trifluoperazine (TFP). Treatment of PC12 cells with 1-oleoyl-2 acetylglycerol also leads to increases in the phosphorylation and enzymatic activity of tyrosine hydroxylase; 1,2-diolein and 1,3-diolein are ineffective. The effects of forskolin on the activation and phosphorylation of the enzyme are independent of Ca2+ and are not inhibited by TFP. Forskolin elicits an increase in cyclic AMP levels in PC12 cells. The increases in both cyclic AMP content and the enzymatic activity and phosphorylation of tyrosine hydroxylase following exposure of PC12 cells to different concentrations of forskolin are closely correlated. In contrast, cyclic AMP levels do not increase in cells treated with PMA. Tryptic digestion of the phosphorylated enzyme isolated from untreated cells yields four phosphopeptides separable by HPLC. Incubation of the cells in the presence of the Ca2+ ionophore ionomycin increases the phosphorylation of three of these tryptic peptides. However, in cells treated with either PMA or forskolin, there is an increase in the phosphorylation of only one of these peptides derived from tyrosine hydroxylase. The peptide phosphorylated in PMA treated cells is different from that phosphorylated in forskolin-treated cells. The latter peptide is identical to the peptide phosphorylated in dibutyryl cyclic AMP-treated cells. These results indicate that tyrosine hydroxylase is activated and phosphorylated on different sites in PC12 cells exposed to PMA and forskolin and that phosphorylation of either of these sites is associated with activation of tyrosine hydroxylase. The results further suggest that cyclic AMP-dependent and Ca2+/phospholipid-dependent protein kinases may play a role in the regulation of tyrosine hydroxylase in PC12 cells. PMID- 2881982 TI - Effect of free malonate on the utilization of glutamate by rat brain mitochondria. AB - Malonate is an effective inhibitor of succinate dehydrogenase in preparations from brain and other organs. This property was reexamined in isolated rat brain mitochondria during incubation with L-glutamate. The biosynthesis of aspartate was determined by a standard spectrofluorometric method and a radiometric technique. The latter was suitable for aspartate assay after very brief incubations of mitochondria with glutamate. At a concentration of 1 mM or higher, malonate totally inhibited aspartate biosynthesis. At 0.2 mM, the inhibitory effect was still present. It is thus possible that the natural concentration of free malonate in adult rat brain of 192 nmol/g wet weight exerts an effect on citric acid cycle reactions in vivo. The inhibition of glutamate utilization by malonate was readily overcome by the addition of malate which provided oxaloacetate for the transamination of glutamate. The reaction was accompanied by the accumulation of 2-oxoglutarate. The metabolism of glutamate was also blocked by inclusion of arsenite and gamma-vinyl-gamma-aminobutyric acid but again added malate allowed transamination to resume. When arsenite and gamma-vinyl-gamma aminobutyric acid were present, the role of malonate as an inhibitor of malate entry into the mitochondrial interior could be determined without considering the inhibition of succinate dehydrogenase. The apparent Km and Vmax values for uninhibited malate entry were 0.01 mM and 100 nmol/mg protein/min, respectively. Malonate was a competitive inhibitor of malate transport (Ki = 0.75 mM). PMID- 2881983 TI - Adrenocortical steroids modify neurotransmitter-stimulated cyclic AMP accumulation in the hippocampus and limbic brain of the rat. AB - Glucocorticoid hormones are known to affect limbic system structures that have high levels of specific receptors for glucocorticoids, especially the hippocampus (HIPP). To understand how glucocorticoids may affect synaptic transmission, we have tested the effects of adrenal removal and glucocorticoid replacement on neurotransmitter-stimulated cyclic AMP accumulation in brain slices from the rat limbic system. Adrenalectomy (ADX) caused an enhancement of vasoactive intestinal peptide (VIP)-stimulated cyclic AMP accumulation in HIPP, amygdala (AMYG), and septum (SEP). In HIPP, ADX increased the cyclic AMP response to isoproterenol (ISOP) and decreased the response to histamine (HIST). In the AMYG and SEP, ADX did not affect significantly the action of ISOP, but ADX did decrease the response to HIST in AMYG. Administration of dexamethasone or corticosterone reversed the effects of ADX on cyclic AMP accumulation in the HIPP. The dexamethasone action on VIP-stimulated cyclic AMP accumulation takes place within 48 h and is most apparent in the mid-range of the VIP dose-response curve. These results demonstrate that glucocorticoids regulate neurotransmitter-stimulated cyclic AMP generation in a fashion that is specific, both for the neurotransmitter involved and for the brain regions affected. PMID- 2881984 TI - Glutamate deficits in Alzheimer's disease. PMID- 2881985 TI - Senile dementia of the Alzheimer type without neocortical neurofibrillary tangles. AB - Senile dementia of the Alzheimer type (SDAT) is typified pathologically by neuritic plaques (NP) and neurofibrillary tangles (NFT) in the neocortex and hippocampus. However, in a large series of cases (60) over age 74 a significant minority (30%) lacked neocortical tangles. In order to determine if these latter cases (Group B) otherwise differ from the majority which have both neocortical plaques and tangles (Group A), various clinical and neuropathological parameters were measured for both groups and the results compared. The following indices were examined: degree of dementia, rate of progression of dementia, age at death, brain weight, cerebral hemispheric weight, cortical cell counts from the frontal, temporal, and parietal lobes, the number of neocortical NP, the number of hippocampal NP and NFT, and the levels of neocortical choline acetyltransferase and somatostatin. The two groups showed no statistically significant differences in any of these categories except for increased numbers of neocortical NP in Group A in midfrontal and superior temporal regions. However, cases in Group A showed greater pathologic abnormality in nearly every parameter, albeit without attaining statistical significance. We conclude that SDAT with neocortical NFT is the same disease as SDAT without them, although the presence of such tangles is associated with a tendency towards greater severity. PMID- 2881987 TI - Population response of midbrain dopaminergic neurons to neuroleptics: further studies on time course and nondopaminergic neuronal influences. AB - In the present study, we examined the effects of the cholecystokinin receptor antagonist, proglumide, on the depolarization-induced inactivation of A9 and A10 dopaminergic neurons produced by repeated administration of a classical antipsychotic drug (dopamine receptor antagonist). In addition, we studied the nature of the effects of acute (1-48 hr) and long-term (7 month) treatment with the butyrophenone neuroleptic haloperidol on both the basal firing rate and population response of dopamine-containing neurons in these 2 regions. Acute oral administration of haloperidol (0.5 mg/kg) results, within 1 hr of administration, in an increase in both the firing rate and number of spontaneously active dopamine neurons encountered in both A9 and A10 regions. These effects of a single treatment persist for a minimum of 6 hr and, with respect to firing rate, are not completely normalized for at least 24 hr. In contrast, 7 month continuous treatment with haloperidol reduces the number of spontaneously active DA neurons encountered in both regions in a manner similar to that observed at 21 d. This effect is inferred to be due to the induction of depolarization-induced inactivation of these neurons, since the acute administration of the normally hyperpolarizing, direct-acting dopamine receptor agonist apomorphine (64 micrograms/kg) immediately reverses this reduced number of cells per track to near control levels. This effect appears to be dependent on the continued presence of haloperidol since, when animals treated for 7 months are sampled 14 d after the cessation of drug administration, spontaneous activity is no different from that observed in age-matched controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881986 TI - The NMDA receptor antagonist 2-amino-5-phosphonovalerate blocks stimulus train induced epileptogenesis but not epileptiform bursting in the rat hippocampal slice. AB - The role of N-methyl-D-aspartate (NMDA) receptors in producing stimulus train induced bursting (STIB) was examined in area CA3 of the rat hippocampus. Extracellular recordings were made from the CA3 pyramidal cell layer. Bursting was induced by trains of electrical stimuli delivered to the stratum radiatum of CA3, or by bath application of NMDA. The specific NMDA receptor antagonist DL-2 amino-5-phosphonovaleric acid (APV) was then bath applied to test its ability to block STIB and NMDA activated bursting. A dose-response relation for NMDA activation indicated that bath application of 1 and 5 microM NMDA had little or no effect on the response to a paired stimulus pulse (triggered response) and did not induce spontaneous bursting. Ten micromolar NMDA induced strong triggered and spontaneous bursting during the application of NMDA in 72% of the slices. Fifty to one hundred micromolar NMDA caused the abolition of the excitatory postsynaptic potential (EPSP) and orthodromic population spike and the decrease or abolition of the antidromic population spike. In the normal medium wash following 10 microM NMDA, those slices that produced triggered and spontaneous bursting in 10 microM NMDA underwent an early phase of decreased excitability in which spontaneous bursting occurred in only 6% of the slices that were bursting in NMDA. Later in the wash spontaneous bursting began occurring in half of the slices that were bursting in NMDA, and the excitability of the triggered bursts increased slightly. The ability of the NMDA receptor antagonist APV to block NMDA activated bursting was tested. Bath application of 100 or 200 microM APV alone caused little change in the normal triggered response. When 10 microM NMDA was added to the APV solution, there was little or no change in the triggered response, and no spontaneous bursting occurred. However, when 100 or 500 APV was added to the NMDA solution after NMDA burst activation had occurred, triggered bursting was reduced, but not blocked, although spontaneous bursting was blocked. In those slices that continued bursting after the washout of NMDA, bath application of 100 or 500 microM APV reduced, but did not block, triggered bursting. Spontaneous bursting continued in all slices. The ability of APV to block the induction of bursting by trains of electrical stimuli was then tested.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2881988 TI - Peptidergic modulation of neuronal circuitry controlling feeding in Aplysia. AB - We examined the effects of 3 neuropeptides and the bioactive amine 5-HT on identified motoneurons (B15 and B16) and interneurons (B4, B5) involved in the control of feeding behavior in Aplysia californica. The application of egg-laying hormone (ELH), small cardioactive peptide b (SCPb), and 5-HT elicits distinct patterns of synaptically induced bursting in the neurons, while PheMetArgPheamide (FMRFamide) inhibits firing due to synaptic activity. Repetitive IPSPs recorded in B15 and B16 are induced by 5-HT and SCPb and inhibited by FMRFamide. The substances also may act directly: In solutions that block synaptic transmission SCPb excites B15, ELH excites B16, 5-HT excites B15, B16, and B4, and FMRFamide both inhibits B15 and B16 and excites B4. We suggest that the output of a buccal ganglion central pattern generator may be modulated to produce distinct patterns of motoneuron activity by these candidate transmitters. We also noted differences in the intrinsic properties of the 2 motoneurons. B15 contains SCPb immunoreactivity while B16 does not. This finding suggests that B15 may be the source for the SCPb immunoreactivity previously found at the ARC muscle and that SCPb may be acting in an autocrine mode. Also, B15 has a significantly lower resting potential than B16 and contains a large transient outward (Ia-like) current. The candidate transmitters act by exciting or inhibiting elements at every level within the hierarchically organized motor system that controls feeding. This expands the diversity of behavioral repertoires that may be elicited from a particular neural circuit. PMID- 2881989 TI - Long-term potentiation in the hippocampus using depolarizing current pulses as the conditioning stimulus to single volley synaptic potentials. AB - The conditions responsible for the associative properties of long-term potentiation (LTP) were examined in the CA1 region of the hippocampal slice preparation. Intracellularly recorded EPSPs resulting from single-volley stimulation at low frequency (0.15-0.1 Hz) in the stratum radiatum or oriens were paired with depolarizing current pulses (50-100 msec) injected through the recording microelectrode. It is shown that these EPSPs, when paired with pulses of sufficient magnitude, become potentiated. This potentiation generally reached a peak after 20-30 pairing events and could outlast the conditioning period by more than 1 hr. It was specific to the paired input, was blocked by 2-amino-5 phosphonovalerate (APV) and was largely blocked by prior homosynaptic tetanization (and vice versa). In experiments performed with picrotoxin (PTX) in the bath, EPSPs were potentiated using 2-4 nA current pulses, with somewhat higher values in normal solution. The effective current pulses, in both normal and PTX solution, produced a repetitive spike discharge of 7-11 spikes (per 100 msec), and within this range, higher frequencies were associated with larger potentiations. However, since similar degrees of EPSP potentiation were observed following blockade of spike activity by intracellular QX-314, spike activity was not the primary conditioning factor. For the potentiation to appear, the EPSP had to occur together with the current pulse or precede it by less than about 100 msec. No potentiation was observed when the EPSP immediately succeeded the pulse. The results suggest that the cooperativity aspect of LTP is related to a need for sufficient postsynaptic depolarization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2881990 TI - Modulation of the flavin-containing monooxygenase in guinea pigs by ascorbic acid and food restriction. AB - Modulation of the flavin-containing monooxygenase (FMO) by varying the ascorbic acid and food intake was investigated. Hepatic activity of the FMO in ascorbic acid-deficient guinea pigs fed a restricted amount of diet which resulted in a 10 15% body weight loss, was 17% of that in animals fed restricted amounts of the adequate diet. FMO hepatic activity in ascorbic acid-supplemented guinea pigs on a food-restricted regimen was 176% of that found in animals fed the adequate diet ad libitum. This increase in activity was not related to stress. Alteration in the activity of this important drug-metabolizing enzyme system by a combination of ascorbic acid deficiency and reduced food intake could potentially alter the rate of metabolism of a great variety of pharmaceutical drugs and environmental chemicals. PMID- 2881991 TI - The neurohistochemistry of neuroregulators in the dental pulp. PMID- 2881992 TI - Pain relief for the pediatric surgical patient. AB - Modern techniques available for the relief of pain following major surgical procedures or trauma in childhood receive scant attention in pediatric surgical textbooks. A range of options for pain relief have been offered to children in our hospital, which include: regional analgesia; appropriate use of intermittent intramuscular narcotic injections; and variable-rate intravenous narcotic infusions. Since 1982 regional analgesia has been used in more than 2,000 patients following operations on the penis and in the inguinoscrotal region. Two hundred forty five children with fractured femora have been managed using femoral nerve blocks. Intermittent intramuscular narcotic injections are the most common method of pain relief. However, the variable nature of children's pain frequently results in an unsatisfactory outcome. Variable-rate intravenous narcotic infusions were introduced in 1982 and the first 155 infusions in 144 patients have been analyzed. The protocol and method of administration are described along with the dosage and problems encountered during the introduction of the technique. It has now been employed postoperatively in 242 more patients and many infusions have been commenced in the emergency department, intensive care, and neonatal units bringing the total number of infusions to more than 600. Assessment of effective pain relief has been made on the basis of observation and comment by parents and patients and by medical and nursing staff. The steady increase in demand for the use of this technique is an index of its value. It is concluded that there is a real need to improve pain relief for children by better education of medical and nursing staff and inclusion of this important subject in pediatric surgical text books. PMID- 2881993 TI - Depressant action of oxybutynin on the contractility of intestinal and urinary tract smooth muscle. AB - Experiments were carried out in-vitro using segments of guinea-pig ileum, taenia caeci, ureter and detrusor. In the ileum, oxybutynin (30, 100 nM) competitively antagonized acetylcholine-induced contractions but did not alter those induced by histamine. Higher concentrations of oxybutynin (up to 10 microM) induced a non competitive depression of responses to both agonists and caused a parallel shift to the right of the Ca2+-induced contractions in taenia caeci strips bathed in a Ca2+-free, high-K+ medium. In the ureter, oxybutynin (1-10 microM) impaired rhythmic muscular contractions in normal medium and after CaCl2 addition in Ca2+ free medium. Similarly to verapamil (10, 30 microM), oxybutynin (10, 30 microM) depressed both the cholinergic and non-adrenergic, non-cholinergic components of the electrically-induced contractions of detrusor strips. It is concluded that oxybutynin has anticholinergic properties and, at higher concentrations, exerts a direct spasmolytic activity possibly mediated by blockade of the transmembrane Ca2+ fluxes responsible for smooth muscle contraction. PMID- 2881994 TI - Adrenergic receptor subtype activation by (+)-, (-)- and (+/-)-norephedrine in the pithed rat. AB - The ability of (+/-)-norephedrine (phenylpropanolamine) and its component isomers, (+)-and (-)-norephedrine, to activate adrenergic receptor subtypes in the cardiovascular system of the urethane/chloralose-anaesthetized pithed rat has been investigated. At all adrenoceptor subtypes, (-)-norephedrine was the most potent agonist followed by (+/-)- then (+)-norephedrine. The greatest activity was observed at the alpha 1-receptor, with little activity observed at either beta 1 or beta 2-adrenoceptors. Reserpinization shifted the (-)-norephedrine dose response curve slightly to the right, indicating that only a minor portion of its activity is due to the release of stored endogenous catecholamines. These results suggest that most of the cardiovascular activity of the compounds is through the direct activation of alpha 1-adrenoceptors. PMID- 2881995 TI - Sodium nitroprusside: pharmacological aspects of its interaction with hydroxocobalamin and thiosulphate. AB - Hydroxocobalamin (HOCb), when mixed with sodium nitroprusside (SNP) in a 10:1 or 1:1 molar ratio and injected (i.v.) into the anaesthetized rat, prolonged the depressor response to SNP by 25-50%, but did not affect the degree of blood pressure lowering. Both the 'onset' and 'offset' components of the response were prolonged. Injecting [14C]SNP along with a 10-fold molar excess of HOCb resulted in a 2- to 3-fold elevation of plasma radioactivity which was maintained during the first 10 min of a 40 min experimental period. These effects of HOCb on the pharmacodynamics and pharmacokinetics of SNP are probably due to complex formation between the two compounds. Sodium thiosulphate (ST) added to SNP (12:1 molar ratio) had no effect on the depressor response to SNP. This mixing of ST and SNP had a less-marked influence on the plasma [14C] SNP-derived radioactivity than occurred with HOCb. There was no initial elevation of radioactivity, but the levels were raised by 50-60% at 4, 6 and 10 min. Since the depressor response to SNP was unaffected by ST, it is presumed that the higher concentrations of radioactivity were due to inactive degradation products rather than the active species itself. PMID- 2881996 TI - Differences in the promotion mechanism of the colonic absorption of antipyrine, phenol red and cefmetazole. AB - The promotion of antipyrine, phenol red and cefmetazole absorption by sodium ethylenediaminetetraacetate (EDTA-Na) as a paracellular promoter, diethyl maleate (DEM) as a transcellular promoter, and sodium taurocholate (TC-Na), whose promotion mechanism is still unclear, has been investigated by the rat in-situ colonic loop technique. All these promoters increased AP absorption and water influx from the lumen to the blood. Ouabain treatment suppressed the increase in antipyrine absorption and water influx induced by TC-Na and EDTA-Na, but did not modify the enhancing effect of DEM. Thus, the promotion mechanism of TC-Na may be similar to that of EDTA-Na. Phenol red and cefmetazole absorption were increased by TC-Na and EDTA-Na but not by DEM. Accordingly, phenol red and cefmetazole absorption appears to be promoted via paracellular but not transcellular routes. The collection of blood for plasma samples reduced the influx of water which had been increased by TC-Na or EDTA-Na. Consequently, the enhancement in antipyrine plasma concentration by these promoters was reduced to the control level. The inhibitory mechanism for this is discussed on the basis of the blood-flow limitation of antipyrine and water absorption. PMID- 2881998 TI - Erythrocyte binding of cephalosporins. AB - A rapid sample preparation and HPLC technique was used to study the erythrocyte binding properties of six cephalosporins at therapeutic concentrations. The negligible red blood cell partition coefficients indicated that only small amounts of the cephalosporins were taken up by the blood cells at all drug concentrations. Thus, plasma concentrations were about twice as high as the respective blood concentrations. Blood/plasma ratios solely depended on the haematocrit and were independent of the extent of protein binding. PMID- 2881997 TI - Does brain 3,4-dihydroxyphenylacetic acid reflect dopamine release? AB - After sulpiride (75 mg kg-1) administration, a significant increase in dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) occurred in the rat striatum. No attenuation in the sulpiride-induced dopamine and DOPAC increase was seen in the striatum from rats previously treated with benztropine (25 mg kg-1). On the other hand, in the benztropine + sulpiride-treated group, HVA levels were significantly lower compared with those of rats to which only sulpiride had been given. The results presented suggest that under appropriate conditions, as when sulpiride is used, dopamine can be deaminated before its release has occurred. PMID- 2881999 TI - Inhibitory effect of phenothiazines on the binding of [3H]perazine to alpha 1 acid glycoprotein. AB - A system is described which allows the determination of the affinity constant of unlabelled drugs to alpha 1-acid glycoprotein (alpha 1-AGP) by displacing [3H]perazine from the binding protein with equilibrium dialysis. All drugs investigated appear to bind to only one site at the alpha 1-AGP molecule. From experiments, in which the chemical structure of the displacers was varied, the fragment 21-31 of the amino acid sequence appears to be a candidate for hydrophobic interactions. The glutamic acids 177 and 178 of the alpha 1-AGP molecule could be involved in ionic interactions with the side chain of phenothiazine derivatives. The relevance of alpha 1-AGP for drug binding, distribution, and the possible reasons for insufficient correlation between psychotropic plasma concentration and therapeutic response is discussed. PMID- 2882000 TI - The effect of phenylpentenyl-khatamines on the release of radioactivity from rat striatal tissue prelabelled with [3H]dopamine. AB - The CNS-stimulating properties of leaves of the khat shrub (Catha edulis, Celastraceae) are presumed to be due mainly to (-)-cathinone, a phenylpropylamine alkaloid that has been shown to have an amphetamine-like releasing effect at physiological catecholamine storage sites. Recently, several phenylpentenylamine alkaloids have been identified in khat leaves, and these have been evaluated, in vitro, in the present study for their ability to induce release of radioactivity from [3H]dopamine-prelabelled rat striatal tissue. It was found that the phenylpentenylamines have a weak releasing effect, and are therefore considered unlikely to play an important role in the stimulating properties of khat leaves. PMID- 2882001 TI - Effect of lapachol, a naphthaquinone isolated from Tectona grandis, on experimental peptic ulcer and gastric secretion. AB - Lapachol, a naphthaquinone isolated from the roots of Tectona grandis given at a dose of 5 mg kg-1 p.o. twice daily for 3 days was found to have an anti ulcerogenic effect on subsequently induced experimental gastric and duodenal ulcers in rats and guinea-pigs. Its action appears to be associated with an effect on the protein content of gastric juice, and it reversed aspirin-induced changes in peptic activity, protein and sialic acid. PMID- 2882002 TI - Anticholinergic activity of the dopamine receptor agonist, TL-68 (N,N-dipropyl-2 aminotetralin). AB - The anticholinergic properties of a dopamine receptor agonist, a non-hydroxylated derivative of N,N-dipropylaminotetralin (TL-68), were evaluated using the guinea pig isolated tracheal strip and rat phrenic nerve-diaphragm preparations. TL-68 competitively antagonized carbachol-induced contractions in guinea-pig trachea with a pA2 value of 5.88 +/- 0.05. In the rat phrenic nerve-diaphragm preparation, TL-68 was found to be inactive in blocking nicotinic cholinergic receptors. PMID- 2882003 TI - The anticoagulant activity of some selected warfarin analogues. AB - The anticoagulant activities of 6-, 7-, 8-, 4'-hydroxy, 6-chloro- and 6 bromowarfarin were determined in rabbits after intraperitoneal administration of 16.2 mumol kg-1 over 96 h. Substitution on the 4-hydroxycoumarin moiety resulted in reduction of the anticoagulant activity. 6-Chlorowarfarin was more potent than 6-bromowarfarin suggesting that the molecular size of 4-hydroxycoumarin moiety may be crucial for biological activity. PMID- 2882004 TI - Influence of water deprivation on the disposition of paracetamol. AB - The effect of acute (96 h) water deprivation on the disposition of paracetamol (acetaminophen) has been examined in male Sprague-Dawley rats. Plasma and urinary concentrations of the drug and its two major metabolites, the glucuronide and sulphate, were determined by a sensitive and specific high performance liquid chromatographic assay. Following an intravenous dose of 100 mg kg-1 of paracetamol, no significant changes were found in the elimination rate constant (k), the mean residence time (MRT), total plasma clearance (Cl) and the apparent volume of distribution at steady-state (Vss). However, rats deprived of water for 96 h excreted a larger percentage of the administered dose as the glucuronide conjugate (15.3 vs 7.9%) and a smaller percentage as unchanged paracetamol (7.3 vs 20.7%) in the urine. In addition, there was a significant two-fold increase in the partial metabolic clearance to paracetamol glucuronide. Water deprivation also led to a significant reduction in the renal clearance of paracetamol accompanied by an increase in the renal clearance of the glucuronide. PMID- 2882005 TI - Temporal changes in bupivacaine kinetics. AB - The chronokinetics of bupivacaine have been examined in the mouse. Different groups of adult male NMRI mice maintained under controlled environmental conditions received a single intraperitoneal injection of bupivacaine (20 mg kg 1) at one of four different fixed time points in a 24 h period i.e. 10:00, 16:00, 22:00 and 04:00 h. Blood samples were taken 0.25, 0.5, 0.75, 1, 1.5, 3, 4 and 6 h after drug administration and total serum levels of bupivacaine were determined by a gas-liquid chromatography with a flame ionization detector. Statistically significant temporal changes were found in the following pharmacokinetic parameters: highest Cmax value = 0.900 +/- 0.080 micrograms mL-1 at 22:00 h (amplitude, maximum-minimum/mean X 100, is 64%); highest Cmax/Tmax ratio = 3.596 +/- 0.339 at 22:00 h (amplitude = 85%); highest beta elimination half-life, T1/2 beta, = 3.950 +/- 0.246 h at 22:00 h (amplitude = 35%); area under concentration curve (AUC infinity 0) was not found to be significantly different among the hours of administration. The temporal kinetic changes demonstrated suggest a possible circadian difference in bupivacaine efficacy and/or toxicity. PMID- 2882006 TI - Salivary secretion of paracetamol in man. AB - Plasma and saliva paracetamol levels were measured by HPLC in ten healthy volunteers who took a therapeutic dose after an overnight fast. Salivary levels of the drug were consistently and significantly higher than those in plasma for the first 50 min after oral ingestion, but saliva and plasma levels correlated closely during the elimination phase. There was a highly significant correlation between the AUC 0-alpha calculated from saliva and plasma paracetamol concentration-time curves. The elevated saliva/plasma ratio for the first 50 min was not due to loss of paracetamol from plasma during sample preparation, binding to plasma protein or adsorption to the buccal mucosa. Administration of probenecid in an attempt to block possible active secretion of paracetamol into saliva did not significantly alter the saliva/plasma concentration ratio for the first 50 min, but did significantly reduce this ratio in the time period 125-360 min. The experimental data conformed to a recently proposed model in which elevated saliva/plasma ratios during the early stages following oral ingestion were related to ongoing absorption into the arterial system. PMID- 2882007 TI - Evaluation of electrical conductivity-temperature curves using a mathematical model: temperature-dependent changes during thawing of frozen aqueous pharmaceuticals. AB - The information contained in the electrical conductivity curves of pharmaceuticals measured as a function of temperature can be represented by a small set of parameters. This is achieved by approximating the electrical conductivity curve as a number of consecutive steps, using a suitable empirical model. The three parameters describing each step are: transition temperature, slope factor and step height. The validity of the calculated transition temperatures was established by applying the model to electrical conductivity curves measured on aqueous solutions of KCl, NaCl and on a KCl-NaCl mixture. It appears that the transition temperatures calculated for these inorganic salts are in good agreement with the respective eutectic temperatures reported in the literature. Subsequently, the method was applied to the corticosteroids prednisolone sodium succinate and prednisolone disodium phosphate. The mathematical model yields a satisfactory fit for both experimental conductivity curves. The actual consequences of freeze-drying an aqueous solution of prednisolone sodium succinate below and above the respective transition temperatures calculated are discussed in relation to the experimental conductivity data. PMID- 2882009 TI - The in-vitro metabolism of [14C]pentobarbitone and [14C]phenobarbitone by hamster liver microsomes. AB - The metabolism of [14C]pentobarbitone and [14C]phenobarbitone has been reinvestigated using an in-vitro hepatic microsomal system (Syrian hamsters, Aroclor 1254 induction). The incubation system was routinely supplemented with EDTA (1 mM) and a substrate concentration study revealed the metabolism of [14C]pentobarbitone to be concentration-dependent, with the greatest overall metabolism (greater than 50%) occurring at 0.054 mumol per 3.5 mL. With [14C]phenobarbitone as substrate, overall metabolism was extremely low (3%) and independent of substrate concentration. Addition of further cofactors to the incubation mixture at 20 min intervals over an extended period resulted in almost complete metabolism of [14C]pentobarbitone (100 min), 3'-hydroxypentobarbitone and 3'-oxopentobarbitone being identified as metabolites together with many minor, unidentified products. With [14C]phenobarbitone as the substrate, cofactor addition up to 120 min resulted in 8% overall metabolism; p-hydroxyphenobarbitone was identified as a product of metabolism; other minor products were unidentified. The metabolism studies failed to produce a metabolite having the properties of the N-hydroxylated product of either [14C]pentobarbitone or [14C]phenobarbitone within the detection limits available (0.02% of 0.5 mumol per incubate). PMID- 2882008 TI - Plasma protein binding-lipophilicity relationships: interspecies comparison of some organic acids. AB - Relationships between plasma protein binding of 11 organic acids (benzoic and phenylacetic acid derivatives) and their lipophilicity were studied in man, rabbits, rats and mice. For description, the relationship fu = 1/(1 + aDb) was developed, where fu is the fraction of the unbound drug in plasma, D is the partition coefficient octanol/water and a and b are parameters. While the value of the parameter a is widely different in interspecies comparison, the value of the parameter b is very close in all species studied and is approximately equal to 1. The model used allows the simple calculation of the extent of plasma binding of structurally similar drugs from their lipophilicity, or conversion of the extent of plasma binding from one species to another. PMID- 2882010 TI - Influence of solvent on the availability of testosterone propionate from oily, intramuscular injections in the rat. AB - The suggestion that the biological response to an oily intramuscular injection of testosterone ester is regulated by rapid accumulation of the steroid in body fat, followed by a slow release, has been tested by comparing the release rates of 14C labelled testosterone propionate from different solvents following intramuscular injection into rats. Disappearance from the injection site was rectilinearly related to in-vitro partition coefficients, but elimination of radioactivity in urine and faeces was significantly longer, and the same for all four solvents. Testosterone and testosterone propionate were found in equal concentration in body fat, 2 and 3 days after injection, but their concentrations were too low to form an effective depot. It is suggested that the delay in release, and the independence of the delay on the nature of the solvent is a consequence of biliary recycling of testosterone. PMID- 2882012 TI - The use of large pinch graft technique in a traumatic foot wound. A case report. PMID- 2882011 TI - Fate of haem after parenteral administration of haem arginate to rabbits. AB - Rabbits were injected either intravenously or intramuscularly with [14C]haem arginate and [59Fe]haem arginate (haem 5 mg kg-1). The main part (80%) of AUCINF of labelled haem was associated with the beta-phase, T1/2 being about 6 h. Only 1% of the haem dose had been taken up by the red blood cells. In contrast, the iron moiety from the haem molecule was effectively utilized. Thirty days post injection of [59Fe]haem arginate, 40% of the dose after intravenous injection and 60% after intramuscular injection was circulating with the red cells. Radioactivity was shown to concentrate in the liver, where haem is mainly metabolized and eliminated. An accumulation of haem in the adrenals was also evident. Haem itself did not concentrate in the bone marrow, and a negligible amount of radioactivity was recovered from brain, implying a poor penetration of the blood brain barrier. PMID- 2882013 TI - Renal effects of selective alpha-1 and alpha-2 adrenoceptor agonists in conscious, normotensive rats. AB - The effects of the selective alpha-1 adrenoceptor agonist, cirazoline, and the selective alpha-2 adrenoceptor agonist, B-HT 933, were assessed on renal hemodynamics and on water and solute excretion in conscious, chronically instrumented rats. Infusion (i.v.) of equipressor doses of cirazoline and B-HT 933, 0.04 and 4 mg/kg/hr, respectively, decreased renal plasma flow without changing glomerular filtration rate. Cirazoline infusion did not affect urinary excretion of water, electrolytes or total solutes. In marked contrast, B-HT 933 increased urine flow and sodium excretion significantly (P less than .01) but did not significantly alter potassium and urea excretion. Urine osmolality decreased to hyposmotic levels (from 613 +/- 86 to 172 +/- 8 mOsmol/kg of H2O) during the infusion of B-HT 933, suggesting a possible interaction between the alpha-2 adrenoceptor agonist and the vasopressin system. This diuretic action of the selective alpha-2 adrenoceptor agonist was also observed after the i.v. infusion of a subpressor dose (0.4 mg/kg/hr) of B-HT 933. In rats treated with the ganglionic blocker, hexamethonium (10 mg/kg i.v.), the B-HT 933-induced diuresis was not affected, confirming an action in the periphery, possibly at the level of the kidney. These results suggest that stimulation of renal alpha-2 adrenoceptors in conscious, euvolumic rats modulates the reabsorption of water and sodium at the site of the renal nephron. PMID- 2882015 TI - Pharmacologic evaluation of a cyclic somatostatin analog with antagonist activity at mu opioid receptors in vitro. AB - The cyclic somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2(CTP) was evaluated for agonist and opioid antagonist actions and receptor selectivity in two bioassays: electrically stimulated guinea pig isolated ileum (GPI) and mouse isolated vas deferens (MVD). CTP (100, 300, 1000 nM) produced concentration dependent antagonism of the mu agonist [Me-Phe3,D-Pro4]morphiceptin (PL017) in both the GPI and MVD. Schild analysis of the interactions between CTP and PL017 indicated competitive antagonism between these peptides (Schild slope GPI -0.97 +/- 0.16, Schild slope MVD -1.4 +/- 0.4), and also suggested that the mu receptors in the two tissues are not different (pA2 GPI 7.1 +/- 0.17, pA2 MVD 6.9 +/- 0.16). The effects of the delta selective agonist [D-Pen2,D-Pen5]enkephalin in the MVD were not antagonized by CTP. Likewise, in the GPI, CTP did not antagonize the kappa agonist (trans-3-4-dichloro-N-methyl-N-(2-(1 pyrrolidinyl)cyclohexyl)benzenea cetamine (U50, 488H). In comparison, naloxone antagonized both PL017 and U50,488H in the GPI, as well as [D-Pen2,D Pen5]enkephalin and PL017 in the MVD. In the MVD, CTP also exerted weak somatostatin-like actions (35% maximal inhibition) that could not be demonstrated in somatostatin-tolerant tissues. It also showed inhibitory actions at very high concentrations (3000 and 10,000 nM) that were blocked by both naloxone and the delta antagonist N,N-diallyl-Tyr-AIB-AIB-Phe-Leu-OH (ICI 174,864). ICI 174,864 antagonized [D-Pen2,D-Pen5]enkephalin in the MVD, but did not affect PL017. These results indicate that CTP is a selective mu receptor antagonist in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882016 TI - Systemic and regional hemodynamic characterization of alpha-1 and alpha-2 adrenoceptor agonists in pithed rats. AB - In pithed rats, blood pressure dose-response curves to i.v. cirazoline, methoxamine and phenylephrine (full alpha-1 adrenoceptor agonists) exhibited higher maxima than those to B-HT 920, M-7, UK-14,304 (full alpha-2 adrenoceptor agonists) and indanidine (Sgd 101/75: partial alpha-1 adrenoceptor agonist). For an 80 mm Hg increase in blood pressure, full alpha-1 adrenoceptor agonists enhanced total peripheral, renal and mesenteric vascular resistances significantly more than alpha-2 adrenoceptor stimulants or indanidine. In contrast, all compounds produced a similar degree of hindquarter vasoconstriction, suggesting that both types of alpha adrenoceptors have the same functional importance in this skeletal muscle vascular bed. Application of a multivariate discriminant analysis to the drug-induced changes in the total peripheral and mesenteric vascular resistances associated with a pressor effect of 80 mm Hg allowed their assignment to two distinct groups corresponding to the full alpha-1 and the full alpha-2 adrenoceptor agonists plus indanidine. All investigated compounds in low doses increased cardiac output, which returned to base-line values after high doses of alpha-1 but plateaued after high doses of alpha-2 adrenoceptor agonists or indanidine. alpha-1 adrenoceptor agonists decreased whereas alpha-2 stimulants and indanidine successively increased and then decreased renal blood flow. Finally, all investigated compounds increased hindquarter blood flow at low doses but decreased it at high doses. The ratios of the doses of cirazoline required to produce a 100% rise in systemic and local vascular resistances in the presence or in the absence of prazosin were of similar magnitude. This was also true for M-7 when studied in the presence or in the absence of yohimbine. These findings suggest pharmacological identity within alpha-1 as well as within alpha-2 adrenoceptor populations in all investigated vascular beds. Finally, the calcium entry blocker diltiazem did not affect the increases in systemic and regional resistances evoked by cirazoline but depressed profoundly the effects of M-7 and indanidine. In conclusion, full alpha-1 and alpha-2 adrenoceptor agonists can be discriminated easily on the basis of their systemic and regional hemodynamics in the pithed rat. That the hemodynamic effects of the partial alpha-1 adrenoceptor agonist indanidine are similar to those of alpha-2 adrenoceptor agonists and susceptible to calcium channel blockade suggests that the alpha-1 adrenoceptors stimulated by this drug have the same coupling modality as alpha-2 adrenoceptors and share with the latter the same functional expression when stimulated. PMID- 2882014 TI - CPP, a selective N-methyl-D-aspartate (NMDA)-type receptor antagonist: characterization in vitro and in vivo. AB - 3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) was synthesized as a rigid analog of 2-amino-7-phosphonoheptanoate, a previously known antagonist at the N-methyl-D-aspartate (NMDA) preferring, or NMDA-type, of excitatory amino acid receptor. CPP was found to be a potent, selective and competitive antagonist of NMDA-type receptors. CPP antagonized with an IC50 of 8 muM [3H]ACh release which was evoked from rat striatal brain slices by NMDA (50 muM). In contrast, the release of [3H]ACh evoked by elevated KCI was not inhibited by CPP even at a concentration of 100 muM. The antagonism by CPP of NMDA-evoked [3H]ACh release was competitive, with a pA2 of 5.66 for CPP, compared with a pA2 value of 5.22 for 2-amino-7-phosphonoheptanoate. CPP affected neither the uptake of L [3H]glutamate nor the inhibition by aconitine of L-[3H]glutamate uptake, suggesting a lack of membrane-stabilizing or local anesthetic effects, and also suggesting that CPP itself may not be taken up through the L-glutamate membrane transporter. Moreover, [3H] CPP was not accumulated by synaptosomes (P2 fraction) which avidly accumulate L-[3H]glutamate, supporting the concept that this NMDA type receptor antagonist acts at an NMDA-type receptor on the external surface of the plasma membrane. CPP (10 muM) failed to interact with any of 21 other putative neurotransmitter receptors including alpha-[3H]amino-3-hydroxy-5 methylisoxazole-4-propionic acid binding (quisqualate-type receptor) and [3H]kainate binding (kainate-type receptor). Audiogenic convulsions in DBA/2 mice were blocked by CPP (ED50 = 1.5 mg/kg i.p.) as were NMDA-induced seizures in CF-1 mice (ED50 = 1.9 mg/kg i.p.). In both strains, CPP impaired the traction reflex at higher doses (ED50 = 6.8 mg/kg and 6.1 mg/kg and 6.1 mg/kg i.p. for DBA/2 and CF-1, respectively). The traction reflex impairment by CPP may be due to muscle relaxant effects of the compound, an explanation supported by the finding that CPP reduced muscle tone as assessed by electromyogram measurement in animals whose muscle tone had been increased by opiate administration. Finally, cerebellar cyclic GMP levels, known to be sensitive to neurotransmission via NMDA type receptors, were decreased by CPP (ED50 = 4.7 mg/kg i.p.) in mice. In conclusion, based upon the competitive antagonism by CPP of NMDA-evoked [3H] ACh release in vitro and the antagonism of NMDA-induced convulsions in vivo, the data presented are consistent with competitive antagonism of NMDA-type receptors. PMID- 2882017 TI - Comparative study of phenothiazine derivatives on monoamine metabolism--direct correlation between the concentrations of drugs and monoamine metabolites in the brain. AB - The pharmacokinetics (distribution and elimination) and pharmacodynamics (biochemical effects on monoamine systems) of phenothiazines including the novel compound, E-0663 (10-[3-(3-hydroxypyrrolidinyl)-propyl]-2-trifluoromethyl phenothiazine), in the central nervous system were investigated concurrently in mice using high-performance liquid chromatography with electrochemical detection. The elimination rate of E-0663 from the brain was longer than that of the classical compounds, chlorpromazine, perphenazine and triflupromazine. The phenothiazine (0.01-100 mumol/kg i.v.) increased the metabolites of catecholamines. Direct correlation analysis was applied to the intracerebral concentrations of the drugs and monoamine-related substances. Significant correlations were observed between the concentrations of drugs and dopamine metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid). The relative potency of the drugs for the effect on the extraneuronal process was promethazine less than chlorpromazine less than E-0663 less than triflupromazine less than perphenazine by covariance analysis. On the other hand, noradrenaline metabolite (3-methoxy-4-hydroxyphenylethylene glycol) also revealed a significant correlation, and the potency was highest in the case of E-0663. These results suggest that E-0663 possessed different pharmacokinetic profiles and a different spectrum in its action on monoamine metabolism from classical phenothiazines. The method described here is simple for comparing the real potency and is useful as a new approach in the biochemical pharmacology of centrally acting drugs. PMID- 2882018 TI - Differences in synaptic efficacy at neuromuscular junctions in frog twitch muscles. AB - A comparison was made of neuromuscular junctions in cutaneous pectoris and cutaneous dorsi muscles of Rana pipiens in order to study mechanisms controlling synaptic efficacy. Other than a small difference in junctional size, the two muscles were structurally and functionally very similar. Despite these similarities, cutaneous pectoris junctions had substantially higher synaptic safety margins. With intracellular recording, it was apparent that the difference in safety margin was due to a large difference in transmitter release. In low Ca2+ solutions, levels of evoked and spontaneous release were 4 times higher in the cutaneous pectoris. When corrected for differences in nerve terminal size at identified junctions, there remained a 3-fold difference in evoked release and a 6-fold difference in spontaneous release per unit terminal length. Differences in normal Ringer solution were 1.8- and 2.5-fold for evoked and spontaneous release, respectively. There was no simple relationship between synaptic efficacy and the total amount of nerve terminal supported by each motoneurone in different frog muscles. We concluded that there can be large differences in synaptic efficacy without correlated structural differences visible with the light microscope. PMID- 2882021 TI - Your CE topic this month (No. 21). Current angina treatment. PMID- 2882019 TI - The probability of quantal secretion along visualized terminal branches at amphibian (Bufo marinus) neuromuscular synapses. AB - The number of quanta secreted from selected sites along terminal branches at toad (Bufo marinus) neuromuscular junctions was determined. Terminal branches were visualized by prior staining with the fluorescent dye, 3-3 Diethyloxadicarbocyanine iodide (DiOC2(5)); neither impulse conduction nor quantal release were affected by DiOC2(5) at concentrations less than 10 microM. The evoked quantal release recorded with an extracellular micro-electrode (me) at different sites along the length of terminal branches was determined in an external calcium concentration, [Ca]o, of 0.35-0.45 mM. For short branches (40-80 microns), me remained approximately constant for over 60% of the branches; for the rest, me declined approximately exponentially with an average length constant of 17 +/- 2 microns (mean +/- S.E. of mean). For both medium (81-120 microns) and long branches (121-160 microns), me declined in nearly all cases approximately exponentially with length constants of 39 +/- 5 and 54 +/- 8 microns respectively. These changes in me were observed at synapses having a wide range of terminal branching patterns. Some DiOC2(5)-stained branches possessed discontinuous cholinesterase staining. In general, me declined along these branches in the same way as along DiOC2(5)-stained branches with continuous cholinesterase staining. It is suggested that because of the decline in me along most medium and long terminal branches, many release sites have a very low probability for secretion in low [Ca]o. Release sites near the point of nerve entry, which have a relatively high probability, therefore make the main contribution to secretion recorded with an intracellular micro-electrode. As a consequence, transmitter secretion from the whole terminal does not fluctuate from impulse to impulse as much as expected if there were a large number of release sites, each with a low probability of secretion. Transmitter secretion then follows binomial rather than Poisson statistics. PMID- 2882020 TI - Properties of rat medial septal neurones recorded in vitro. AB - Activity of neurones of the rat medial septal nucleus (m.s.) was recorded in in vitro slice preparations. The recorded population could be divided into low (less than 30 M omega)- and high-input-resistance (greater than 30 M omega) neurones. The high-resistance neurones tended to fire spontaneous action potentials and post-synaptic potentials. Some of the spontaneously active cells fired rhythmically at rates of 2-10 Hz. The rhythmicity disappeared following hyperpolarization of the recorded cell. The cells could fire repetitive Ca2+ spikes in the presence of tetrodotoxin (TTX) and intracellular Cs+. Cd2+ blocked this rhythmicity. Most of the m.s. cells had a non-linear voltage-current relation in both the hyperpolarizing and depolarizing directions. Hyperpolarizing rectification was selectively blocked by extracellular Cs+ whereas depolarizing rectification could be blocked by TTX. A recovery from hyperpolarization was associated in many cells with a transient depolarization (anodal break (a.b.) potential). A 20 ms 15 mV hyperpolarization could trigger an a.b. potential. The a.b. potential was reduced by TTX and Cs+ but not by Cd2+ or Mn2+. Depolarization of quiescent neurones triggered action potential discharges. A common pattern of discharge was a burst of two spikes which kept a fairly constant interspike interval. The second spike in a doublet could not follow a rate of 10 Hz depolarizing current pulses. It was also sensitive to topical application of Cd2+. It is therefore suggested that Ca2+ might be involved in the generation of the doublet. Long depolarizing current pulses produced trains of action potentials, showing little accommodation and little after-hyperpolarization, indicating that these cells possess little Ca2+-dependent K+ current. Many cells emitted spontaneous post-synaptic potentials at high rates. These could be blocked by picrotoxin. Stimulation of the lateral septal (l.s.) nucleus produced a Cl-dependent i.p.s.p. The i.p.s.p. was blocked by picrotoxin. Topical application of gamma-aminobutyric acid (GABA) produced a marked Cl(-)-dependent increase in conductance. It is suggested that l.s. projects a GABA-mediated inhibitory connexion to the m.s. Acetylcholine (ACh) depolarized m.s. neurones and caused an increase in input resistance. The response was present in TTX or Cd2+-containing medium. Atropine blocked responses to ACh. 5-Hydroxytryptamine (5 HT) hyperpolarized m.s. neurones in a manner consistent with an increase in K+ conductance. The effects of 5-HT were seen in TTX- and Cd2+-treated m.s. slices.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2882022 TI - Tensile strength of postceramic solder joints with a palladium-silver alloy. PMID- 2882023 TI - Electrocortical spectrum power effects of different classes of neuroleptics in rats. AB - In freely moving rats the effects on behaviour and ECoG spectrum power of different classes of neuroleptics (phenothiazines, butyrophenones and benzamides) after systemic and intraventricular administration were studied. Chlorpromazine and haloperidol given systemically or microinjected into the third cerebral ventricle produced behavioural and ECoG slow-wave sleep (SWS) accompanied by a significant increase in ECoG total voltage power as well as in the lower frequency bands; haloperidol was found to be more powerful in inducing behavioural and SWS. In contrast, equimolar doses of 1-sulpiride given systemically or higher doses microinjected into the third cerebral ventricle did not produce significant behavioural and ECoG changes. Thus, the present experiments confirm that neuroleptic drugs may possess a different ECoG profile depending on their structure and provide further evidence concerning the role played by dopaminergic mechanisms in the control of sleep-arousal. PMID- 2882024 TI - Lymphocytotoxins in vasculitis. Correlation with clinical manifestations and laboratory variables. AB - Twenty-eight of 53 patients with various types of vasculitis were found to have cold reacting lymphocytotoxins (LCT). LCT were cytotoxic to both peripheral blood B and T cells as well as to OKT4 and OKT8 subpopulations. The interaction with the B cells was more pronounced than with the T cells as shown by reactivity with the former at higher serum dilutions than with the latter. Similar results were obtained with eluates from the unseparated lymphocytes and from B or from T cells. Partial purification of LCT demonstrated that they belong to the IgM class. LCT correlated with the level of circulating immune complexes as determined by the fluid phase C1q binding assay, but they did not correlate with the level of immunoglobulins, complement or antinuclear factors. The presence of LCT correlated significantly with the activity but not with the disease duration or the number of involved organs. Correlation of LCT with the activity of vasculitis implies that these cytotoxins may have a pathogenetic role and perhaps may serve as a marker for disease activity. PMID- 2882025 TI - Affinity labels for beta-adrenoceptors: preparation and properties of alkylating beta-blockers derived from indole. AB - New alkylating ligands derived from indole with high affinity for beta adrenoceptors were synthesized and their properties examined. N8-(Bromoacetyl)-N1 [3-(4-indolyloxy)-2-hydroxypropyl]-(Z)-1,8-dia mino-p- menthane (8) and its N1,N8 isomer (9) were prepared by the reaction of bromoacetyl bromide with a product of the condensation of 4-indolyl glycidyl ether with (Z)-1,8-diamino-p-menthane. A similar reaction employing 2-cyano-4-indolyl glycidyl ether yielded the respective cyano derivatives 10 and 11. Apparent affinities (Ki, M) for beta adrenoceptors on membrane preparations from rat heart and lung were 4.6 X 10(-10) and 1.34 X 10(-9) for 8, 2.3 X 10(-8) and 4.5 X 10(-9) for 9, 6.1 X 10(-10) and 1.49 X 10(-9) for 10, and 1.83 X 10(-9) and 2.78 X 10(-9) for 11, respectively. When membranes were preincubated with the above ligands (1 X 10(-8) M, 30 min, 30 degrees C) and then washed extensively, reduction in the concentration of specific binding sites of [3H]dihydroalprenolol ranged from 7% to 76% and there was no change in KD of the remaining binding sites. (+/-)-Alprenolol and (-) isoproterenol, but not (+)-isoproterenol, when included with the alkylating ligands in the preincubation mixtures, prevented the reduction in concentration of [3H]dihydroalprenolol binding sites. Compounds 8-11 alone did not stimulate adenylate cyclase activity in rat heart homogenates. However, these compounds inhibited (-)-isoproterenol-stimulated adenylate cyclase activity with Ki values ranging between 5 X 10(-9) and 60 X 10(-9) M. These results suggest that high affinity irreversible beta-adrenergic antagonists were obtained that may be useful for in vivo studies of beta-adrenoceptors. PMID- 2882026 TI - Role of the (acyloxy)methyl moiety in eliciting the adrenergic beta-blocking activity of 3-(acyloxy)propanolamines. AB - Some totally aliphatic 3-(acyloxy)propanolamines were synthesized with the aim of testing whether beta-blocking activity could be obtained from this class of drugs, even in the absence of an aromatic group. The significant and, in most cases, competitive beta-blocking activity shown by the compounds under examination, together with the results of a theoretical study in which their reactivity was compared with that of other adrenergic beta-blocking drugs, seems to confirm a hypothesis previously advanced on the basis of knowledge about the action mechanism of adrenergic beta-blocking drugs and of the results of structural studies. It was also possible to suggest some considerations about the role played by the (acyloxy)methyl portion of 3-(acyloxy)propanolamines in eliciting their adrenergic beta-blocking activity. PMID- 2882027 TI - Protracted severe immune dysregulation induced by cardiopulmonary bypass: a predisposing etiologic factor in blood transfusion-related AIDS? AB - A large percentage of patients with blood transfusion related AIDS received their transfusion during cardiac surgery requiring cardiopulmonary bypass. We hypothesized that the procedure of cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery might be associated with severe immune dysregulation and hence predispose this group in particular to the acquisition of blood transfusion transmitted AIDS. T-cell subset enumeration and their ratio (T4/T8) and T-cell function (local GVH reaction) were serially studied before, during, and 1 and 6 days after surgery in 15 patients undergoing cardiac surgery requiring CPB, in 10 patients undergoing cancer resections (CA), and 11 patients without cancer undergoing elective, non-cardiac general surgical procedures (GEN). Compared to the preoperative values, a significant decline (p less than 0.002) in T4/T8 ratios occurred during CPB (1.63 +/- 0.80 vs 2.55 +/- 0.95), during CA (1.26 +/- 0.71 vs 1.81 +/- 0.72), and during GEN procedures (1.18 +/- 0.59 vs 1.64 +/- 0.68). T4, T8, and T4/T8 ratios returned to preoperative values in both the CA and GEN groups by the first postoperative day; in contrast, T4/T8 ratios remained significantly depressed (p less than 0.05) in CPB patients on the first and also on the sixth postoperative days when compared to preoperative values. This sustained depression in T4/T8 ratios is attributable to a significant increase in the proportion of T8 (suppressor cell) subset in the CPB patients which persisted through the sixth postoperative day. In contrast, in CA and GEN, the proportion of T8 subset returned to the preoperative level by the sixth postoperative day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882029 TI - American Academy of Implant Dentistry Research Foundation. 1st Annual Symposium. Implant dentistry forefront, '85. PMID- 2882030 TI - Laboratory study on the mosquito larvicidal properties of leaf and seed extract of the plant Agave americana. AB - Experiments on the leaf extract tested against three mosquito species led to 100% mortality of stage 4 Anopheles, Aedes and Culex larvae at a concentration of 0.08% within 24-48 h, whereas 100% mortality of stage 1 larvae occurred at lower concentrations: 0.0032% for Aedes aegypti, 0.016% for Culex quinquefasciatus and 0.08% for Anopheles stephensi, and was more rapid. At the end of 24 h, the highest dilution of the seed extract studied (1:200) produces a larval mortality of 100% for Anopheles and Aedes and 56% for Culex spp., when 4th instar larvae were exposed at room temperature. The comparative mortality in the control group was negligible. One hundred per cent mortality of Anopheles larvae took place by the end of 10 h, and of Aedes larvae by 17 h, at a dilution of 1:200 with water. PMID- 2882031 TI - Polyorchidism discovered as testicular torsion associated with an undescended atrophic contralateral testis: a surgical solution. AB - We report a case of polyorchidism presenting as torsion of the supernumerary testis associated with an undescended atrophic contralateral testis. Biopsies of both descended testes revealed a normal histological pattern with active spermatogenesis. After the testicular torsion was corrected, one of the supernumerary testes was placed in the contralateral empty hemiscrotum and the undescended atrophic testis was removed. The aesthetic and functional results were excellent. PMID- 2882032 TI - Akathisia and head and body rocking in schizophrenia. PMID- 2882028 TI - H+-ATPases from mitochondria, plasma membranes, and vacuoles of fungal cells. PMID- 2882033 TI - Ventricular tachyarrhythmia associated with psychological stress. The role of the sympathetic nervous system. AB - Psychological stress has been reported to be a risk factor for sudden cardiac death in individuals both with and without underlying structural heart disease. From a group of 80 patients presenting with life-threatening ventricular tachyarrhythmia, six were identified without underlying structural heart disease. Five of these six patients experienced marked psychological stress. Each of these five patients underwent arrhythmia evaluation, demonstrating recurrent rapid monomorphic ventricular tachycardia related to changes in tone of the sympathetic nervous system. Subsequently, solitary beta-adrenergic blocker therapy was given to each patient. During therapy, four of the five patients had a marked reduction of both arrhythmia and symptoms during a follow-up ranging from 29 to 49 (mean, 38) months. PMID- 2882034 TI - [The effect of pancuronium and vecuronium on isolated tracheal smooth muscle of the guinea pig]. PMID- 2882035 TI - [The effects of pancuronium and vecuronium on urinary catecholamine excretion during upper abdominal surgery]. PMID- 2882036 TI - [Pretreatment dose of vecuronium and its effect on succinylcholine-induced fasciculations and neuromuscular blockade]. PMID- 2882037 TI - Multiple endocrine neoplasia IIA found at autopsy. AB - A case is presented of a 32-year-old black female who died from adult respiratory distress syndrome with disseminated intravascular coagulopathy. At autopsy she was found to have typical multiple endocrine neoplasia IIA, a combination of medullary carcinoma of the thyroid, bilateral adrenal pheochromocytoma and nodular hyperplasia of the parathyroid. PMID- 2882038 TI - [New technology in immuno-serological tests]. PMID- 2882039 TI - [Serum immunosuppressive acidic protein (IAP) in patients with hematological disorders]. PMID- 2882040 TI - [Somatostatin- and neuropeptide Y-immunoreactive cortical neurons in senile dementia of Alzheimer type]. PMID- 2882041 TI - Isolation of DNA clones revealing restriction fragment length polymorphisms in the human genome. PMID- 2882042 TI - [Role stress and fatigue in Japanese middle managers]. AB - Forty-nine middle managerial personnel in a local government office near Tokyo provided data with respect to the moderating effects of satisfaction variables on the relationship between role stress (including role conflict, role ambiguity and role overload) and fatigue. Using the moderated regression technique for data analysis, it was found that the relationships between both role conflict and ambiguity and fatigue were moderated by the managers' satisfaction with the job, itself. Even those who experienced role overload did not report fatigue or dissatisfaction. Implications of these findings for future research, job management and avoidance of stress are discussed. PMID- 2882043 TI - [Information transmission and mechanism of receptors in smooth muscle]. PMID- 2882045 TI - [Pharmacotherapy in the prevention of ischemic heart disease]. PMID- 2882044 TI - Enzyme pathology of human mesotheliomas. AB - In samples of 16 surgically resected mesotheliomas arising from the pleura of the human lung, 6 enzymes from different metabolic pathways, DNA, and mitotic frequency were quantified. The mesotheliomas, irrespective of cell type or grade, showed lower gamma-glutamyl transpeptidase (GGT) concentration than 36 of the 38 pulmonary adenocarcinomas. The mean concentration of this enzyme in the 15 mesotheliomas was an eighth of that in the 56 carcinomas, whereas their DNA content was similar. The quantitative correlation of thymidine kinase (TK), uridine kinase (UK), and phosphoserine phosphatase to mitotic frequency was highly significant for mesotheliomas, as well as for carcinomas. As estimated from their TK [and its recently established quantitative correlation to volume doubling time (DT)], the DT of the 16 mesotheliomas ranged from 50 to over 700 days, with a somewhat longer median than the median for pulmonary carcinomas. Subject survival, though shortest for the 2 sarcomatous mesothelioma cases, varied over an overlapping range for mesotheliomas with epithelial or mixed cell type. The biopsy samples' TK and UK concentrations, however, showed a significant inverse correlation with months of survival after diagnosis. Survival time after the first appearance of symptoms decreased linearly (on log scales) with TK concentration (P less than .001) over the 14 cases. The results of this first quantitative study of a spectrum of biochemical constituents of mesotheliomas identify GGT as an enzyme whose measurement guards against mistaking mesotheliomas and adenocarcinomas for one another and show that the TK concentrations of these mesothelioma samples bear a highly significant, inverse correlation to the postdiagnosis survival time of the individual subjects. PMID- 2882047 TI - The effects of somatostatin and SMS 201-995 on experimentally-induced pancreatitis and endotoxaemia in rats and on monocyte activity in patients with cirrhosis and portal hypertension. PMID- 2882046 TI - [Metipranolol 0.1% and pilocarpine 2% as a fixed combination compared to each substance alone in the treatment of glaucoma. A controlled, randomized clinical study comparing the intraindividual effects and tolerance]. AB - A fixed combination of pilocarpine 2% and metipranolol 0.1% was found to have a better pressure-lowering effect than pilocarpine 2% alone or metipranolol 0.1% alone, as well as being tolerated well, both subjectively and objectively. In many cases only the fixed combination was successful in lowering intraocular pressure to tolerable values. PMID- 2882048 TI - Interaction between opiates and somatostatin and their role in vagally-induced acid secretion. PMID- 2882049 TI - Clinical effect of dopamine on incidence of peptic ulceration. AB - Dopamine and its agonists diminish gastric acid secretion and exert a protective effect on experimentally induced peptic ulcers in rats. For treatment of peptic ulcer disease in man, dopamine and dopamine antagonists have been recommended, but clear evidence is not yet available. To answer the question of whether dopamine has any protective effect regarding peptic ulcer formation in man, autopsy reports were evaluated for the incidence of acute peptic ulcerations before and after the introduction of dopamine as a common drug in intensive care units. The analysis showed no change in ulcer incidence, i.e., our retrospective study demonstrated no ulceroprotective action of dopamine in critically ill patients. PMID- 2882050 TI - Anti-ulcer drugs in antisecretory doses for "cytoprotection" in arthritic patients? AB - Gastric injury and dyspepsia are major side-effects of acetylsalicylic acid (ASA) or most non-steroidal anti-inflammatory drugs (NSADs) which cause either gastric ulcerations or gastroduodenal erosions. There is only a limited number of trials in which the possibility of preventing or treating gastric lesions due to those drugs have been studied in man. This paper reviews trials in which H2-receptor antagonists, pirenzepine and prostaglandins have been investigated. - Pirenzepine given in antisecretory doses seems to improve gastrointestinal symptoms induced by ASA or NSADs. Cimetidine and misoprostol might prevent fecal blood loss. Gastroduodenal lesions might be prevented by pirenzepine, misoprostol and enprostil. It might be possible that cimetidine or ranitidine heal NSAD-induced peptic ulcers better than placebo in arthritic patients who stop the ingestion of NSADs. - All over the results of the cited trials are inconclusive, since the number of patients studied were too small and the design of almost all trials was incomparable. Furthermore, all cited studies do not correspond to Robert's concept of "cytoprotection", since H2-blockers, pirenzepine and prostaglandins have been applied in antisecretory doses in man. PMID- 2882051 TI - Cytoprotective properties of somatostatins. AB - Secretion of many hormones is inhibited by regular cyclic somatostatin-14. Since additional cytoprotective properties of this hormone have been described, the question arises of whether analogs of somatostatin with increased endocrine activity may also exert increased cytoprotective activity. It could be shown that the endocrine and the cytoprotective property of somatostatin-14 must have different modes of action. In analogs of somatostatin with increased endocrine activity the cytoprotective effect is also increased. A maximal increase in the cytoprotective effect of certain analogs of somatostatin is accompanied by a loss of endocrine activity. PMID- 2882052 TI - Influence of somatostatin on galactosamine-induced liver injury. PMID- 2882053 TI - Somatostatin analogs with improved oral bioavailability. AB - Cyclic hexapeptide analogs of somatostatin with insulin, glucagon, and growth hormone (GH) release inhibitory potencies of 50-200 times those of somatostatin have been synthesized. Replacement of the Phe-7 residue with histidine has resulted in increased oral bioavailability and duration of action. Metabolic degradation of L-Trp containing analogs upon oral administration has also been overcome by incorporation of histidine. The all L-amino acid containing analog cyclo(NMePhe-His-Trp-Lys-Val-Ala) shows oral bioavailability comparable to D-Trp containing analogs. PMID- 2882054 TI - Common structural features for cytoprotection activities of somatostatin, antamanide and related peptides. PMID- 2882055 TI - Prevention of phalloidin-induced lesions on isolated rat hepatocytes by novel synthetic analogues of somatostatin. AB - Exposure of freshly isolated hepatocytes to phalloidin produced blebs on their surfaces: this phenomenon was time- and dose-dependent and irreversible. When hepatocytes were pretreated with somatostatin or with some of its synthetic analogues, formation of blebs was dramatically reduced. This cytoprotective effect was dose-dependent: the dose-response profiles enabled the determination of the CD50 values, i.e., the concentrations of analogues that yielded 50% cytoprotection. The analogues with sequences of amino acids in the retro form, compared to those in somatostatin-14, exhibited higher cytoprotection; the retro hexapeptide, cyclo(-Phe-Thr-Lys-D-Trp-Phe-D-Pro-), was 27 times more active than somatostatin-14. Specificity of cytoprotection was examined by pretreating hepatocytes with biologically active peptide hormones prior to exposure to phalloidin. On a molar basis, prolactin and thyroid-stimulating hormone possessed activity comparable to that of somatostatin-14, whereas glucagon was twice as active. Insulin, vitamin A and propranolol exercised less than 10% protection. The synthetic analogues of somatostatin are potent protective agents against cell lesions induced by phalloidin. Formation of blebs on hepatocytes by toxins and their prevention by agents of interest may serve as a suitable morphological assay for screening of cytotoxicity and cytoprotection. PMID- 2882057 TI - Protection against duodenal ulceration by somatostatins. AB - The purpose of our investigation was to study the effect of two somatostatin analogs (SMS 201-995 and 008) on duodenal ulcer disease induced by cysteamine in rats. Male Wistar rats were given cysteamine (28 mg/100 g body wt.) by rubber stomach tube three times in a single day. All animals of the test group were injected subcutaneously either with SMS 201-995 in different doses or with 008. On the 3rd day stomach, duodenum, and adrenal glands were macroscopically examined for lesions (duodenal ulceration, gastrointestinal bleeding, adrenal hemorrhage). Our results showed a dose-dependent effect of SMS 201-995 on the mortality, incidence, and intensity of cysteamine-induced duodenal lesions in rats. The incidence and the intensity of gastrointestinal bleeding and adrenal hemorrhage were also dose-dependently reduced by SMS 201-995. There was no definite effect of 008 on the mortality, incidence, or intensity of cysteamine induced duodenal ulceration. PMID- 2882056 TI - Molecular aspects of cytoprotection by modified somatostatins. AB - Somatostatin and cyclic modifications of this molecule inhibit the development of protrusions on the surface of isolated hepatocytes in presence of phalloidin. This prevention of phalloidin injury is caused by competitive inhibition of the phallotoxin uptake. Transport inhibition is not a hormonal effect of somatostatin. The concentrations needed are in the micromolar range. The most protective somatostatin modifications lack hormonal activity (GH release). Somatostatin and its analogs are substrates of a hepatocellular transporter which also translocates other cyclopeptides, among them phalloidin, antamanide, and several organic anions, such as iodipamide and fusidic acid. Physiological substrates of this multispecific transport system are bile acids. The protection of phallotoxin injury by somatostatin is a specific mechanism only representative for liver cells. No other cell contains the above multispecific transporter. PMID- 2882058 TI - Gastric mucosal protection by somatostatins. AB - Somatostatin and somatostatin derivatives were tested for their ability to prevent gastric hemorrhagic erosions induced by ethanol. The somatostatin analogues were cyclohexapeptides with the rearranged amino acids 7-14 of somatostatin (S-14): Phe-Thr-Lys(Z)-Trp-Phe-D-Pro(I), Phe-Thr-Lys-Trp-Phe-D Pro(II), Phe-Thr-Lys-D-Trp-Phe-Tyr(III) and Tyr-Phe-D-Trp-Lys-Thr-Phe(IV). In Spraque-Dawley rats receiving ethanol alone, the lesions involved 18.1 +/- 3.2% of the glandular stomach while after S- 14 (10(-7) mol/rat) the lesioned area was reduced to 6.3 +/- 1.1% (p less than 0.05). Peptide I and peptide II (doses 10( 7) -10(-9) mol/rat) decreased the area of erosions to less than 5%. Peptide III was less active and peptide IV was inactive. In rats with chronic gastric fistula S- 14 and peptide II decreased the cysteamine-stimulated acid secretion without affecting the pepsin output. We also continuously measured the intraluminal pH in the stomach of Wistar rats which develop gastric erosions after subcutaneous injection of cysteamine. The erosions were reduced by S- 14 or SMS while the intraluminal pH did not change under the influence of cysteamine or the combination of cysteamine plus S- 14 or SMS. Thus some of the peptides derived from S- 14 exert prominent gastric mucosal protection without influencing gastric secretion. PMID- 2882059 TI - [New possibilities of heterozygote detection of hemophilia A]. AB - Hemophilia A is the most common inherited bleeding disorder in man. The recent isolation of the hemophilia gene has led to the identification of an intragenic restriction fragment length polymorphism (RFLP) which can be used for segregation analysis in families at risk for carrying the disease. In addition, a tightly linked extragenic RFLP can also be used for these analyses. In this paper, we exemplify the usefulness of DNA analysis in genetic counseling of families at risk for hemophilia A. Although DNA analysis allows carrier detection in the majority of families, bioassays are still required for accurate diagnosis when DNA analysis is not informative. PMID- 2882060 TI - Influence of chronic omeprazole treatment on gastric endocrine function. AB - The influence of a 4-week treatment with the substituted benzimidazole omeprazole (20 mg daily) or placebo on gastric endocrine function was tested in healthy male volunteers. Compared with placebo-treated subjects basal serum gastrin levels were slightly but significantly increased after treatment with omeprazole from 10 to 22 pg/ml (medians; P less than 0.05) but returned to pretreatment values after 2 weeks recovery (9 pg/ml). Antral gastrin tissue concentration increased and was still elevated after recovery; however, antral gastrin concentrations also increased in placebo controls, and increments immediately after cessation of omeprazole treatment (2.58 micrograms/g; median) were not significantly over control values (1.92 micrograms/g; P greater than 0.1). Postprandial gastrin release, basal and food-stimulated insulin release, antral somatostatin concentration, and volume densities of antral G and D cells were unaffected. It is concluded that, due to incomplete inhibition of gastric acid secretion at the omeprazole dose studied, only slight effects on the endocrine stomach are to be expected after 4 weeks of administration of omeprazole. PMID- 2882061 TI - [Antacids and muscarinic and histamine H2 receptor blockaders in the treatment of peptic ulcer]. PMID- 2882062 TI - [Experiences with interdisciplinary round-table conferences on the topic of interdisciplinary activities. Only constant effort will lead to the target]. PMID- 2882064 TI - A case of wound botulism. PMID- 2882063 TI - Prions causing nervous system degeneration. PMID- 2882066 TI - [Effects of acute and chronic treatment with an adrenergic alpha receptor agonist, LE S3341, on the rate of catecholamine turnover in various peripheral organs and brain structures in the rat]. AB - The turnover of catecholamines (CA) in some peripheral tissues and various areas of the rat brain was estimated by measuring the amine depletion after inhibition of their biosynthesis by alpha-methyl-p-tyrosine (alpha-MPT). Acute or chronic treatment with S3341 (3mg/kg i.p.) reduced NA turnover in submaxillary glands, brain stem and rest of the brain but had no effect on NA turnover in the hypothalamus. The dopamine (DA) levels were unaltered following chronic S3341 treatment but the alpha-MPT induced disappearance of DA was significantly retarded in the striatum and rest of the brain. The results of the present study demonstrate that no tolerance to the effect of S3341 on brain CA turnover develops during chronic drug administration. The central biochemical effects of S3341 appear different from those of other agonists of central alpha 2 adrenoceptors such as clonidine. PMID- 2882065 TI - [Anti-cerebral edema properties of PEG 300 in triethyltin poisoning]. AB - The polyethylene glycols (PEG) frequently used as solvents of non hydrosoluble molecules present toxic and pharmacodynamic properties. The effect of PEG 300 (10 ml/kg) on the modifications of the central nervous system (CNS) previously induced by a subchronic intoxication with triethyltin salt (TEE) (2 mg/kg p.o. for 5 days) has been studied in rat. The following parameters are recorded: measure of brain edema, concentration of the aminergic neurotransmitters in four different brain areas, neurological status, behaviour, mortality. The PEG 300 antagonizes or reduces some of the effects of the TEE: edema, behavioral disturbances, mortality. On the opposite, no change in the amines and their metabolites induced modifications is observed. This selective antagonism towards some of the components of TEE brain toxicity brings more information on pharmacological properties of this solvent and opens a discussion on the role of neurotransmitters on brain edema. PMID- 2882067 TI - Expression of the HT462 antigen on fresh leukemic T cells and on cells of HTLV-I infected lines. AB - We have examined expression of antigens defined by HT462 monoclonal antibody (mAb), together with other HTLV-I related antigens using phorbol 12-myristate 13 acetate treated leukemic mature T cells. Thirteen patients with adult T-cell leukemia (ATL), 3 patients in remission states of ATL and 5 patients with non-ATL were examined. All ATL cells expressed the HT462 antigen, however cells from patients in remission did not express the HT462 antigen. A low percentage of cells from 2 out of 5 patients with non-ATL mature leukemic T cells expressed the HT462 antigen, although these cells did not express other HTLV-I related antigens. Cells of HTLV-I infected human cell lines expressed the HT462 antigen. Three HTLV-I infected rat cell lines (TARS-1, TART-1, TARL-2) did not express the HT462 antigen, although cells of these lines expressed other HTLV-I related antigens. Characterization of the HT462 antigen by strip radioimmunoassay based on western blotting technique using cell lysates of HUT102 cells revealed two additional bands (p68, p35) together with previously reported proteins (gp52, p42). Only p68 was seen in western blots using cell lysates of the rat cell lines. These findings further suggest that the HT462 antigen is a cellular component induced in virus transformed human cells and not a virus encoded protein. PMID- 2882068 TI - Quantitative analysis of cytotoxicity induced by HTLV-I carrying cells against a human lymphoblastoid cell line, Molt-4. AB - Co-cultivation of HTLV-I carrying cells and virus-free lymphoid cells resulted in the cytopathic effect and cytotoxicity of the latter cells. Microscopically, these phenomena were observed as early as 2 h as the appearance of multinuclear giant cells and ballooning cells with striking resemblance with cytopathic changes induced by HTLV-III. When the cytopathic effect and cytotoxicity of the target cells by HTLV-I carrying cells were assayed by 51Cr-release assay system, these phenomena were quantitatively analysed and the cytotoxic activity was observed generally in HTLV-I positive cells. Virally induced cytotoxicity was inhibited by plasma of adult T-cell leukemia (ATL) patients specifically. Cytotoxic activity of HTLV-I positive cell lines was correlated with HTLV-I antigen expression of them. HTLV-I negative cell lines did not express cytotoxicity significantly. PMID- 2882069 TI - [Treatment of post-traumatic osteomyelitis with Taurolin Gel]. PMID- 2882070 TI - [Evaluation of the management of multiple injuries in our hospital]. PMID- 2882071 TI - [Surgical management of pathological fractures of the humerus]. PMID- 2882072 TI - [Treatment of pillion fractures of the tibia]. PMID- 2882074 TI - [Evaluation of operations on hallux rigidus performed by the author]. PMID- 2882073 TI - [Traumatic arteriovenous fistulas of the arm]. PMID- 2882075 TI - [Changes in the inequality of the length of extremities after varus osteotomy of the femur in Perthes disease]. PMID- 2882076 TI - [Restoration of the opposition of the thumb by transfer of the musculus extensor indicis proprius tendon]. PMID- 2882078 TI - [Management of a comminuted forearm fracture using an external fixation device]. PMID- 2882077 TI - [Diagnosis and successful treatment of a closed rupture of the pulmonary artery]. PMID- 2882079 TI - [Plate osteosynthesis of a double ring fracture of the pelvis]. PMID- 2882080 TI - [Spondylolysis in osteopetrosis]. PMID- 2882082 TI - Regular alcohol use raises blood pressure in treated hypertensive subjects. A randomised controlled trial. AB - 44 men with treated essential hypertension who were moderate to heavy drinkers took part in a randomised, controlled, crossover trial of the effects of alcohol intake on blood pressure. Usual antihypertensive treatment was maintained throughout 6 weeks of normal drinking and 6 weeks of drinking only a low-alcohol beer. Self-reported changes in alcohol consumption (mean [SEM] from 452 [30] ml ethanol/week during normal drinking to 64 [8] ml/week while drinking the low alcohol beer) were confirmed by biochemical measurements. Mean systolic and diastolic blood pressures were significantly lower during the last 2 weeks of the low-alcohol period than during the normal-alcohol period, the mean difference in the supine readings being 5.0 (1.4) and 3.0 (0.9) mm Hg, respectively. Regression analysis suggested that reduction in alcohol intake contributed to the fall in both systolic and diastolic blood pressures independently of changes in weight. Thus, curtailing alcohol intake may lead to improved blood-pressure control and may reduce the need for antihypertensive drugs. PMID- 2882081 TI - Deposits of eosinophil granule proteins in cardiac tissues of patients with eosinophilic endomyocardial disease. AB - Eosinophilic endomyocardial disease is a complication of the hypereosinophilic syndrome and of several other disorders associated with high blood eosinophil counts. Eosinophil granule proteins may be involved in the development of these lesions. This multi-centre study investigated whether these proteins could be demonstrated within the cardiac tissues of eighteen patients with eosinophilic endomyocardial disease. Serial sections of tissue taken at necropsy or at cardiac biopsy were stained for eosinophil major basic protein by indirect immunofluorescence and for eosinophil cationic protein, eosinophil protein-X, and activated eosinophils by means of alkaline-phosphatase-linked monoclonal antibodies. Activated eosinophils and secreted eosinophil granule proteins were most evident within the necrotic and later stage thrombotic lesions and were found mainly within the areas of acute tissue damage in the endocardium and in the walls of small blood vessels. These findings suggest that eosinophil granule proteins are involved in cardiac injury, producing muscle damage and vascular injury which lead to the development of endomyocardial fibrosis. PMID- 2882083 TI - Double-blind controlled trial of single-dose treatment with bovine surfactant in severe hyaline membrane disease. AB - In a double-blind clinical trial the effects of a single dose of reconstituted bovine surfactant ('Surfactant TA') were assessed in 30 premature infants (birthweight 751-1750 g) with severe hyaline membrane disease. 17 infants had a sonicated saline suspension of 100 mg/kg surfactant phospholipid instilled into the trachea at 5.0 (SD 0.7) hours of age and 13 infants received saline by the same route at 4.3 (1.1) hours of age. In the surfactant-treated group there was early improvement in oxygenation and ventilation. Haemodynamically significant patent ductus arteriosus occurred more often in the surfactant group; pneumothorax and pulmonary interstitial emphysema occurred less often. The combined incidence of death and severe bronchopulmonary dysplasia was significantly lower in the surfactant group (3/17) than in the placebo group (9/13). PMID- 2882084 TI - Prevalence of antibodies to human immunodeficiency virus, gonorrhoea rates, and changed sexual behaviour in homosexual men in London. AB - The prevalence of antibody against human immunodeficiency virus (anti-HIV), which rose among British homosexual/bisexual men attending a London sexually transmitted-disease clinic from 3.7% (4/107) in March, 1982, to 21% (26/124) in July, 1984, was 18.1% (17/94) in April/May 1985, 24.5% (61/249) in January, 1986, and 25.3% (25/99) in November/December, 1986. This slower rise in anti-HIV prevalence coincided with a fall in the annual gonorrhoea rate from 15.3% in 1982 to 5.1% in the first half of 1986 in the same male homosexual clinic population. Over the same period a reduction in the number of sexual partners and a change to safer sexual practices has been documented among homosexual and bisexual men taking part in a prospective study of the natural history of HIV infection. These data support the value of continuing preventive efforts to control viral spread in the absence of an effective vaccine or therapy. PMID- 2882086 TI - Neurofibromatosis. PMID- 2882085 TI - Evidence that the gene for tuberous sclerosis is on chromosome 9. AB - Linkage analysis was undertaken in nineteen families with tuberous sclerosis by use of 26 polymorphic markers. All affected members fulfilled strict diagnostic criteria and unaffected members were rigorously investigated to confirm their status. Maximum lod scores were 1.20 for adenylate kinase 1 (AK1) at zero recombination and 3.85 for the ABO blood group at zero recombination (confidence limits 0-0.10). These findings support the assignment of the gene for tuberous sclerosis to the distal long arm of chromosome 9. PMID- 2882087 TI - Midwives of the future. PMID- 2882088 TI - Administration of drugs by the buccal route. PMID- 2882089 TI - Skull x-rays after head injury--the final word? PMID- 2882090 TI - The safe motherhood initiative: a call to action. PMID- 2882092 TI - Reporting obstetric ultrasound. PMID- 2882091 TI - Prospective study of the aetiology and outcome of pneumonia in the community. AB - A prospective one-year study of community pneumonia was conducted in Nottingham. 236 of 251 episodes of pneumonia (defined as an acute lower respiratory tract infection, for which antibiotics were prescribed, associated with new focal signs on examination of the chest) were investigated. Acute radiographic changes were present in 93 (39%). A pathogen was identified in 129 (55%) episodes, with Streptococcus pneumoniae, Haemophilus influenzae, and influenza viruses those most frequently identified. Mycoplasma pneumoniae was uncommon and infection with Legionella pneumophila was found in only 1 episode. Hospital admission was required in 52 (22%) episodes. 7 patients died (3%), all but one of the deaths occurring in patients who had been admitted to hospital. Pneumonia in the community is common but few people die of it. Initial antibiotic therapy should always cover S pneumoniae and H influenzae. PMID- 2882093 TI - Japan's search for international guidelines on rights of mental patients. PMID- 2882094 TI - Maintenance lithium. PMID- 2882095 TI - Combination treatment for falciparum prophylaxis. PMID- 2882096 TI - Lyme disease in Europe and North America. PMID- 2882097 TI - Severe encephalopathy associated with Lyme disease. PMID- 2882098 TI - Antibodies to Borrelia burgdorferi and localised scleroderma. PMID- 2882099 TI - Parvovirus B19 associated with fetal abnormality. PMID- 2882100 TI - Serological definition of new subgroup of patients with autoimmune chronic active hepatitis. PMID- 2882101 TI - Antibodies to liver cytoplasmic protein complex in chronic hepatic disease. PMID- 2882102 TI - Legionnaires' disease: reduction in risks associated with foaming in evaporative cooling towers. PMID- 2882104 TI - Trials in acute stroke. PMID- 2882103 TI - European collaborative trial of multifactorial prevention of coronary heart disease. PMID- 2882105 TI - HTLV-I-related agent and non-Hodgkin lymphomas in married couple. PMID- 2882106 TI - Diabetics and renal failure. PMID- 2882107 TI - Oocyte donation and gamete intrafallopian transfer as treatment for premature ovarian failure. PMID- 2882108 TI - Simplified treatment for ovum donation. PMID- 2882109 TI - HIV-2/LAV-2 in Portuguese man with AIDS (Paris, 1978) who had served in Angola in 1968-74. PMID- 2882110 TI - Memory for anaesthesia. PMID- 2882111 TI - Long incubation period for HIV-2 infection. PMID- 2882112 TI - Factor VIII and IX inhibitors after exposure to heat-treated concentrates. PMID- 2882113 TI - Quarantine method for preparation of safe factor VIII blood products. PMID- 2882114 TI - Salt in processed and home-cooked food. PMID- 2882115 TI - Colposcopy. PMID- 2882116 TI - Early-onset and late-onset pneumonias in intensive care units. PMID- 2882117 TI - Maternal health in Third World. PMID- 2882118 TI - Syringe exchange programme for drug addicts. PMID- 2882119 TI - Drug treatment policy. PMID- 2882120 TI - Congenital dopamine beta-hydroxylase deficiency. PMID- 2882122 TI - Sex steroid implants and psychological disorders of the climacteric. PMID- 2882121 TI - Insulin-receptor antibody and hypoglycaemia associated with Hodgkin's disease. PMID- 2882123 TI - Fatty acid saturation index in peripheral blood cell membranes of AIDS patients. PMID- 2882124 TI - Interaction between warfarin and miconazole oral gel. PMID- 2882125 TI - Control of epidemic methicillin-resistant Staphylococcus aureus. PMID- 2882126 TI - Edmund Biernacki and the erythrocyte sedimentation rate. PMID- 2882127 TI - No fault compensation based on patient insurance. PMID- 2882128 TI - Damages for stillborn child. PMID- 2882129 TI - HPV 16 DNA in normal and malignant cervical epithelium: implications for the aetiology and behaviour of cervical neoplasia. AB - Southern blot hybridisation showed that cervical cancer biopsy specimens from 31 of 47 (66%, 95% confidence interval [CI] 52-80%) patients contained HPV 16 homologous DNA sequences, with evidence of integration of viral genome into host cell chromosomes in 7. Normal ectocervical biopsies from 9 of 26 (35%, 95% CI 16 53%) control women contained HPV 16 DNA, and none showed evidence of integration. HPV 16 DNA positivity did not correlate with marital or sexual history, parity, use of oral contraceptives, or smoking habits in cases or controls, or with outcome of treatment in cases. HPV 16 DNA positivity was found less frequently with age less than 40 years old than with age greater than 40 in both cases (p less than 0.05) and controls (p less than 0.01). After age-adjustment there was no significant difference between cases and controls in frequency with which HPV 16 DNA was found. These data suggest that the association between HPV 16 and cervical neoplasia is age-mediated and that the presence of the viral genome may not always warrant intervention. PMID- 2882130 TI - Hypoglycaemia in African children with severe malaria. AB - Hypoglycaemia, defined as a plasma glucose concentration below 2.2 mmol/l, developed in 15 of 47 prospectively studied Gambian children with severe chloroquine-sensitive falciparum malaria. 5 of these hypoglycaemic children died compared with 1 in the normoglycaemic group (p = 0.02). In contrast to previous observations in quinine-treated adults, in whom hypoglycaemia was associated with hyperinsulinaemia, plasma concentrations of insulin were appropriately low and plasma ketones were high. Raised plasma concentrations of lactate and alanine suggested impairment of hepatic gluconeogenesis. In African children, hypoglycaemia is an important and treatable manifestation of severe malaria and is unrelated to antimalarial treatment. PMID- 2882131 TI - Does growth hormone cause relapse of brain tumours? AB - Tumour relapse rates in 14 patients with medulloblastoma, 8 with glioma, 2 with ependymoma, 6 with leukaemia, and 1 with T-cell lymphoma who received growth hormone (GH) treatment for growth failure secondary to cranial irradiation were compared with rates among patients treated with radical radiotherapy for the same types of tumour. Five relapses (in 5 patients) occurred (1 optic nerve glioma, 2 medulloblastomas, and 2 ependymomas), three during and two after completion of GH treatment. Patients with medulloblastoma and ependymoma who relapsed were older at tumour diagnosis, underweight at the start of GH therapy, and entered puberty later than similar relapse-free patients. The late relapse rate of medulloblastoma and glioma was unaltered by GH therapy. Ependymoma carries a poor prognosis, and of the 4 late survivors, the 2 who received GH relapsed. No leukaemic relapse has been associated with GH treatment. The findings indicate that GH therapy does not increase the relapse rate of medulloblastoma, glioma, and leukaemia. PMID- 2882132 TI - Use of enzyme-linked synthetic DNA in diagnosis of falciparum malaria. AB - Plasmodium falciparum contains a family of 21-base-long repetitive DNA sequences in its genome. A 21-base synthetic DNA oligomer, formerly labelled with phosphorus-32 for autoradiographic detection of P falciparum DNA, was covalently coupled to alkaline phosphatase for histochemical detection. The conjugate (PFR1 AP) detected purified P falciparum DNA with a sensitivity and specificity equal to that of 32P-labelled probes after 2-day exposures. PFR1-AP did not detect host DNA or DNA of other Plasmodium species. In African blood specimens PFR1-AP specifically detected P falciparum infections of 100 parasites/microliter. This sensitive, rapid, nonisotopic probe will allow more widespread use of DNA hybridisation in the diagnosis of malaria. PMID- 2882133 TI - Association of alkaline phosphatase with an autoantigen recognised by circulating anti-neutrophil antibodies in systemic vasculitis. AB - A solid phase radioimmunoassay has been developed to detect circulating autoantibodies to neutrophil cytoplasmic antigens in systemic vasculitis. After fractionation of these antigens by size, with gel filtration high performance liquid chromatography, sera from patients with clinically different forms of systemic vasculitis, Wegener's granulomatosis (WG) and microscopic polyarteritis (MP), showed contrasting specificities of binding. WG sera bound to 100, 6.2, and 1.8 kD components, whereas MP sera bound only to the 100 kD component, allowing immunological distinction between the syndromes. The 100 kD component recognised by both WG and MP sera also showed alkaline phosphatase activity. Further evidence for this association was obtained by direct binding experiments between systemic vasculitis sera and calf-intestinal or human neutrophil alkaline phosphatase and by the cross-reactivity of W8, a monoclonal antibody raised to a neutrophil cytoplasmic autoantigen, with various preparations of the enzyme. PMID- 2882134 TI - Medical student numbers and medical manpower. PMID- 2882135 TI - The Health Divide: Swan-song of the Health Education Council. PMID- 2882136 TI - Human papillomaviruses and cervical cancer: a fresh look at the evidence. PMID- 2882138 TI - Why suture the peritoneum? PMID- 2882137 TI - Assessing respiratory disablement. PMID- 2882139 TI - Risk of AIDS after herpes zoster. AB - In a closed internal medicine practice for homosexual men in Central Manhattan herpes zoster developed in 112 men between 1980 and mid-1986. In these patients the incidence of acquired immunodeficiency syndrome (AIDS) was high: Kaplan-Meier survival analysis indicated cumulative incidences of AIDS of 22.8% within 2 years after herpes zoster, 45.5% within 4 years, and an estimated 72.8% after 6 years. Severity of zoster (relative risk, RR = 4.6), degree of pain (RR = 3.4), and zoster of the cranial or cervical dermatomes (RR = 2.2) were all associated with a poor outcome. Oral thrush, oral hairy leucoplakia, amoebiasis, and superficial (tinea) fungal infections also indicated an increased risk of AIDS among zoster patients. Oral thrush and oral hairy leucoplakia manifestations were diagnosed an average of 1.2 and 1.1 years, respectively, after the diagnosis of herpes zoster; thus zoster is an early indicator of an impaired immunity. Herpes zoster can be used as a predictor of AIDS and in AIDS risk groups should be regarded as a poor prognostic sign. PMID- 2882140 TI - Hindbrain hernia headache. AB - In six patients with episodic, severe, and disabling headaches with specific characteristics and in whom clinical examination and CT scanning were normal the symptoms were due to hindbrain herniation into the foramen magnum with resulting craniospinal pressure dissociation. This syndrome may be recognised by eliciting the typical history. In all patients myelography showed hindbrain herniation or Arnold-Chiari deformity and surgical decompression of the foramen magnum produced complete resolution of the headaches. PMID- 2882141 TI - Public health function. PMID- 2882142 TI - Can pertussis be eradicated by vaccination? PMID- 2882143 TI - Human parvovirus B19 infections in United Kingdom 1984-86. PMID- 2882144 TI - Month of birth and prevalence of musculoskeletal diseases later in life. PMID- 2882145 TI - Measures of nutritional status. PMID- 2882146 TI - Rett syndrome: disintegration not dementia. PMID- 2882147 TI - Spinal hyperostosis and etretinate. PMID- 2882149 TI - Epilepsy preceding stroke. PMID- 2882150 TI - Post-stroke depression and recovery after stroke. PMID- 2882148 TI - Vasoactive intestinal peptide producing tumour contains high density of somatostatin receptors. PMID- 2882151 TI - Stroke and atrial fibrillation. PMID- 2882152 TI - Ichthyosis resolving after renal transplantation. PMID- 2882153 TI - Bat rabies and the UK. PMID- 2882154 TI - Lactate transporter defect. PMID- 2882155 TI - Donor-specific transfusion and antibody response. PMID- 2882156 TI - Preventing oesophageal cancer. PMID- 2882157 TI - Adulteration of "street" heroin with chloroquine. PMID- 2882158 TI - Drug abuse. PMID- 2882159 TI - Using confidence intervals. PMID- 2882160 TI - Syringes for diabetics. PMID- 2882161 TI - Certificate in transfusion medicine. PMID- 2882162 TI - Clinical pharmacology and geriatrics. PMID- 2882163 TI - Calcium supplements and osteoporosis. PMID- 2882164 TI - Incidence of colonic lesions in Streptococcus bovis and enterococcal endocarditis. PMID- 2882166 TI - Colposcopy. PMID- 2882165 TI - Management of mildly abnormal cervical smears. PMID- 2882167 TI - Ciprofloxacin resistance. PMID- 2882168 TI - Anaesthesia and surgery in children. PMID- 2882169 TI - Genetics of tuberous sclerosis. PMID- 2882170 TI - Trends in anorexia nervosa. PMID- 2882171 TI - Birth after cryopreservation of unfertilized oocytes. PMID- 2882172 TI - Screening for HIV during pregnancy. PMID- 2882173 TI - Active management of labour. PMID- 2882174 TI - Diltiazem and internal anal sphincter. PMID- 2882175 TI - Juvenile chronic myelogenous leukaemia and histiocytosis syndromes in children. PMID- 2882176 TI - Malignant disorders and long-term survival in haemodialysis patients. PMID- 2882177 TI - Indomethacin and arterial oxygenation in critically ill patients with severe bacterial pneumonia. PMID- 2882178 TI - Court of Appeal agrees to sterilisation of 17-year-old mentally handicapped girl under wardship jurisdiction. PMID- 2882179 TI - C-myc proto-oncogene expression and prognosis in early carcinoma of the uterine cervix. AB - Expression of the c-myc gene was studied by northern blot and slot blot hybridisation in 72 specimens of stage I or II squamous cell carcinoma of the uterine cervix. In 25 of the 72 tumours c-myc proto-oncogene was overexpressed (ie, at levels 4-20 times higher than in normal tissues). Patients whose tumours showed c-myc overexpression had an eight-fold greater incidence of early relapse than the other patients (p = 0.001). The 18-month relapse-free survival rates were, respectively, 49% and 90% for these two groups of patients. PMID- 2882180 TI - Effect of 13-cis-retinoic acid on survival of patients with myelodysplastic syndrome. AB - A randomised therapeutic trial of 13-cis-retinoic acid was carried out in 70 patients with myelodysplastic syndrome having 5% or fewer marrow blast cells. Among non-sideroblastic patients the 1-year survival in the treated group was 77%, compared with 36% in the control group. There were too few deaths among patients with sideroblastic anaemia to allow any effect of therapy on survival to be evaluated. PMID- 2882181 TI - Absence of diabetes in a rural West African population with a high carbohydrate/cassava diet. AB - 1028 (99%) of the 1038 inhabitants of the West African village of Agbave and a random sample of 353 (12.4%) of the population of 2850 in Kati, another West African village, were screened for diabetes. Also recorded were their anthropometric data, dietary habits, possession of antibodies to malaria, and serum IgG concentrations. About 85% of the study population consumed cassava root at least once a day. The mean (SD) capillary random blood glucose concentration was 5.1 (1.1) mmol/l in men and 5.1 (0.6) in women. The mean (SD) body mass index was 20.2 (1.8) in men and 20.7 (2.3) in women. The mean blood glucose was similar whether cassava was consumed once daily, more than once daily, or less than once daily. None of the 1381 subjects examined had diabetes. This finding suggests that a high carbohydrate/cassava intake (84% of a mean daily supply of 1916 calories) combined with a low protein consumption (8% of caloric supply) does not cause diabetes. This does not support the World Health Organisation hypothesis that malnutrition-related diabetes exists, at least not in this West African rural population. PMID- 2882182 TI - Value of visual evoked response and oligoclonal bands in cerebrospinal fluid in diagnosis of spinal multiple sclerosis. AB - To assess the predictive value of prolongation of visual evoked response (VER) plus the presence of oligoclonal bands in the cerebrospinal fluid (CSF) in the diagnosis of multiple sclerosis (MS) in patients with isolated cord lesions, the false-positive rate for the two tests combined was determined by a prospective analysis of 42 patients with a structural spinal cord lesion. The false-positive rate for the combination of VER and CSF abnormalities was zero, but the individual false-positive rates were 10% for VER and 12% for CSF protein oligoclonal bands. According to Bayes' theorem, and taking into account the false positive rates of the tests in the population studied and the prevalence of MS and the true-positive rates for the tests as derived from published reports, abnormalities of VER and CSF protein together gave a probability of MS of 100%. However, if only either the VER or the CSF were abnormal, the probability of MS was 44% or 49%, respectively. An abnormal result for both tests thus indicates a sufficiently high probability of MS to exclude myelography, but a positive result in only one test warrants the procedure. PMID- 2882183 TI - Hepatic glutathione S-transferase release after halothane anaesthesia: open randomised comparison with isoflurane. AB - Plasma concentrations of hepatic glutathione S-transferase (GST) are a more sensitive measure of acute hepatic damage than aminotransferase activity. Plasma GST concentrations have been measured by radioimmunoassay in an open randomised study after halothane or isoflurane anaesthesia. The concentration of GST was significantly increased after anaesthesia in patients who received halothane in 30% oxygen/70% nitrous oxide (n = 37) and in patients who received halothane in 100% oxygen (n = 17). The frequency of abnormal GST concentrations, defined as 4 micrograms/l or more, was 35% and 24%, respectively. GST concentrations usually reached a peak 3-6 h after the end of anaesthesia. In 17 patients who received isoflurane in 30% oxygen/70% nitrous oxide, there was no significant rise in GST concentration and no patient had a concentration above 4 micrograms/l. No patient in any of the groups had a significant increase in alanine aminotransferase. In clinically identical situations, anaesthesia with halothane but not isoflurane leads to demonstrable impairment of hepatocellular integrity. PMID- 2882184 TI - Immune donors can protect marrow-transplant recipients from severe cytomegalovirus infections. AB - To study the importance of transferred immunity against cytomegalovirus (CMV) in allogeneic, HLA-matched, T-cell-depleted bone-marrow transplantation, the incidence, severity, and outcome of CMV infections were studied in 40 CMV seropositive recipients in relation to the donors' immunity against CMV. There was no significant difference in the incidence of CMV infections between recipients of seropositive (n = 27) and seronegative (n = 13) marrow. However, the incidence of CMV pneumonitis (8/13 compared with 4/27; p less than 0.001) and the mortality attributable to CMV infection (6/13 compared with 1/27, p less than 0.01) were significantly greater in the group with seronegative donors than in those with seropositive donors. Multivariate regression analysis showed that recipients of seronegative marrow had a fifteen-fold greater risk of CMV pneumonitis and a fifty-fold increase in risk of a fatal CMV infection than recipients of seropositive marrow. Thus, after T-cell depletion CMV-seropositive marrow protects seropositive recipients against severe CMV infections; whenever possible, therefore, such recipients should be given marrow from seropositive donors. Ultimately, active immunisation of CMV-seronegative donors might help to protect seropositive recipients of T-cell-depleted marrow transplants against severe CMV infections. PMID- 2882186 TI - Pen-sized digital 30-second blood glucose meter. PMID- 2882187 TI - Erythropoietin. PMID- 2882185 TI - Local prostaglandin F2 alpha injection for termination of ectopic pregnancy. AB - In nine women with unruptured ectopic pregnancy, prostaglandin F2 alpha was injected under laparoscopic control into the affected oviduct and in eight patients also into the ovary containing the corpus luteum. Termination of the pregnancy was achieved in all cases (in one at the second attempt), without complications. Fertility after this procedure needs to be compared with that after conventional surgery. PMID- 2882188 TI - The bran wagon. PMID- 2882189 TI - Government's response on prison medical service. PMID- 2882190 TI - Down with waiting lists and times. PMID- 2882191 TI - Outcome of RDS survivors. PMID- 2882192 TI - Bone-marrow transplantation in high-risk acute lymphoblastic leukaemia in first and second remission. AB - Bone-marrow transplantation has been used in patients with acute lymphoblastic leukaemia (ALL) thought to be at high risk of relapse if managed with chemotherapy. Data from 444 ALL patients with one or more high-risk features at diagnosis were analysed to evaluate outcome after HLA-identical bone-marrow transplantation during first or during second remission. The 4-year actuarial probability of leukaemia-free survival was 45% (95% confidence interval 36-54%) for transplants in first remission compared with 22% (15-29%) for those in second remission (p less than 0.0002). The 4-year probabilities of relapse were 26% (14 38%) and 56% (45-67%) respectively (p less than 0.0001). For high-risk ALL, transplantation in first remission had clearly superior results to transplantation in second remission. Further studies are needed to determine whether patients with high-risk ALL should receive transplants during first remission or should initially receive chemotherapy, with transplantation being reserved for patients who relapse. PMID- 2882193 TI - Variations in avoidable mortality and variations in health care resources. AB - It has been proposed that the effectiveness of medical treatment should be measured by mortality from specified diseases for which death is apparently avoidable given appropriate medical intervention. Unfortunately, that proposal was not supported by direct analysis of the relation between health care resources and avoidable mortality--an analysis which is essential for establishing the validity of avoidable mortality as an indicator of the outcome of health care. Thus the proposal does not yet have any basis, theoretical or practical. A more realistic but still oversimple model is now proposed. With presently available data, however, the validity of avoidable mortality is unlikely to be established, even by this model. PMID- 2882194 TI - Health care systems in Greece. PMID- 2882195 TI - The anatomy of large inpatient waiting lists. AB - A survey of 31,224 patients on 33 of the largest inpatient surgical waiting lists in Wales and the West Midlands was undertaken in 1986. 19% of the patients were older than 64 years and over 90% lived within their district of treatment or in an adjacent district. Patients awaiting operations for hernia, varicose veins, arthroscopy, cataract, tonsils and adenoids, or sterilisation made up 45% of the lists. 45% of patients had already waited over a year for treatment, and it was evident that many of the lists had not been properly reviewed. PMID- 2882196 TI - Waiting lists: a surgeon's response. PMID- 2882197 TI - Defective video displays, shields, and skin problems. PMID- 2882199 TI - Statistical analysis of Lipid Research Clinics Program. PMID- 2882198 TI - Serological comparisons of approaches to polio vaccination in the Gambia. PMID- 2882200 TI - Tetanus and altitude. PMID- 2882201 TI - Acupuncture for respiratory disease. PMID- 2882202 TI - Hospital-acquired Acinetobacter baumanii pneumonitis. PMID- 2882203 TI - Chronic malnutrition and deciduous dental caries in Peruvian children. PMID- 2882204 TI - Unexpected lesson from Chernobyl. PMID- 2882205 TI - Long-term vaginal carriage of Chlamydia? PMID- 2882206 TI - Trophoblast cells and maternal blood. PMID- 2882207 TI - Hyperammonaemic encephalopathy in chronic myelomonocytic leukaemia. PMID- 2882208 TI - Treatment for panic. PMID- 2882209 TI - Topical cyclosporin and psoriasis. PMID- 2882211 TI - Routine tests for HIV antigen. PMID- 2882210 TI - Prolonged survival and late presentation of vertically transmitted HIV infection in childhood. PMID- 2882212 TI - Magnetic resonance imaging and smooth periventricular high-signal areas. PMID- 2882213 TI - Coeliac disease and allergic manifestations. PMID- 2882214 TI - Transmission of Toscana virus by sandflies in Italy. PMID- 2882215 TI - Blood dyscrasias and the relative safety of non-narcotic analgesics. PMID- 2882216 TI - Food irradiation. PMID- 2882217 TI - Medical devices and consumer protection. PMID- 2882218 TI - Drug information for patients. PMID- 2882219 TI - Confidentiality of pre-employment health screening. PMID- 2882221 TI - Do patients see visions that talk? PMID- 2882220 TI - Crisis at Christmas. PMID- 2882222 TI - Pancreatic graft failure due to pelvic examination. PMID- 2882223 TI - Combined risk factors and coronary heart disease. PMID- 2882224 TI - Laboratory testing on cerebrospinal fluid. PMID- 2882225 TI - Measures of nutrition. PMID- 2882226 TI - Prostate cancer and androgens. PMID- 2882227 TI - Haloperidol metabolism and antipsychotic effect in schizophrenia. PMID- 2882228 TI - Measured and predicted creatinine clearance. PMID- 2882229 TI - Serological markers for delta hepatitis. PMID- 2882230 TI - Surrogacy, adoption, and custody. PMID- 2882231 TI - Central obesity and coronary heart disease in men. AB - The relation between central body fat distribution, determined by measurement of subscapular skinfold thickness (SSF), and the development of definite coronary heart disease (CHD) was examined after 12 years of follow-up in a cohort of 7692 men who participated in the Honolulu Heart Program. The risk of incident coronary events was directly related to SSF. Compared with men in the lowest tertile of SSF, those in the middle tertile experienced a 70% excess of definite CHD. For those in the highest tertile, the excess more than doubled. For a given level of body mass index (BMI), SSF remains a significant and independent predictor of definite CHD, even after adjustment for age, total cholesterol, glucose, triglycerides, hypertensive status, and cigarette smoking. In contrast, the independent effect of BMI was not significant after adjustment for SSF. Thus centrally obese individuals are at increased risk of CHD, independent of BMI. PMID- 2882232 TI - Periurethral enterobacterial carriage preceding urinary infection. AB - The periurethral enterobacterial flora was identified before infective episodes in 56 patients with recurrent urinary infection. There were 91 episodes of infection, with colonisation by aerobic gram-negative bacilli in 60. In only 31 (34%) episodes were patients colonised with the infective strain. In 31 episodes there was no colonisation of the perineum and in 29 there was heterologous colonisation. In another group of 54 women investigated during an enterobacterial infection of the urine there was colonisation with the infecting organism in 55 (86%) of 64 episodes; in 2 there was no colonisation; and 7 (11%) were associated with a heterologous strain. Women who have recurrent urinary infections are susceptible to perineal and periurethral colonisation with gram-negative bacteria but the infection need not be with the colonising enterobacteria. PMID- 2882233 TI - Monoclonal antibody-based enzyme immunoassay for trypsinogen in neonatal screening for cystic fibrosis. AB - An enzyme immunoassay (EIA) with monoclonal antibodies against human trypsinogen in neonatal blood-spots has been evaluated for screening for neonatal cystic fibrosis (CF). In a retrospective study, 36 of 39 CF samples were distinguished from controls matched for age and storage time. 7 infants with CF were detected in 16,500 infants screened in a prospective study. The EIA is quicker and less labour intensive than conventional assays for the detection of immunoreactive trypsin and may have further advantages of specificity and sensitivity for monitoring the release of pancreatic zymogens in CF. PMID- 2882234 TI - Comparison of endotracheal and peripheral intravenous adrenaline in cardiac arrest. Is the endotracheal route reliable? AB - Twelve patients presenting to an accident and emergency department in asystolic cardiac arrest were randomly allocated to treatment with endotracheal adrenaline (five patients) or peripheral intravenous adrenaline (seven patients). Femoral artery blood samples were taken for assay of adrenaline and noradrenaline. After intravenous adrenaline there was a good clinical and biochemical response, but after endotracheal adrenaline there was no change in serum adrenaline and no measurable clinical response. The endotracheal route of adrenaline administration is not reliable in out-of-hospital cardiac arrest. PMID- 2882235 TI - Proteolipid identified by magnetic resonance spectroscopy in plasma of a patient with borderline ovarian tumour. AB - Magnetic resonance spectroscopy (MRS) can identify abnormal lipoproteins in the plasma of patients with premalignant and malignant tumours. Proteolipid complexes, 8-11 nm and 25-28 nm in size, were isolated from the plasma of a patient with a borderline ovarian tumour. These complexes, which generated a characteristically long MRS T2 relaxation value (greater than 400 ms), were disrupted by ribonuclease. None of the conventional lipoproteins had a T2 value above 160 ms. Chemical analysis of the proteolipid complexes showed a 20% glycolipid component, and MRS identified a fucosylated molecule as the origin of the long T2 value. 9 months after resection of all tumour, a visible lipoprotein band, possibly lipoprotein (a), persisted in the plasma but neither the long T2 relaxation value nor the 8-11 nm or 25-28 nm particles were present. The long T2 relaxation value in the MRS profile, found in isolated proteolipid and unfractionated plasma and serum of other patients with carcinoma of the ovary and colon, provides a non-invasive method of assaying for cancer. PMID- 2882237 TI - New fibreoptic cardiac catheter. PMID- 2882236 TI - Is ursodeoxycholic acid an effective treatment for primary biliary cirrhosis? AB - The effects of ursodeoxycholic acid (UDCA, 13-15 mg/kg body weight daily) were prospectively evaluated in fifteen patients with primary biliary cirrhosis (PBC). The mean concentration of UDCA in serum expressed as the percentage of total bile acids rose from 0% at baseline to 58% (SEM 9%) after 2 years' treatment, whereas total serum bile acid levels did not change significantly. The proportion of patients with pruritus necessitating the use of cholestyramine was significantly lower at 2 years than at baseline. Standard liver function tests improved in all the patients. At 2 years the average activities of gamma-glutamyltranspeptidase, alkaline phosphatases, and alanine aminotransferase and bilirubin levels were reduced (respectively 78%, 65%, 68%, and 36% of pretreatment values). In three patients who agreed to interrupt the ingestion of UDCA for 3 months after 2 years' treatment there was clear deterioration in liver function tests, which again improved after reinstitution of UDCA. These results suggest that long-term UDCA might be a safe and effective treatment for PBC, but a randomised, controlled, double-blind trial is urgently needed. PMID- 2882238 TI - Gene amplification in malignancy. PMID- 2882239 TI - Diagnosis: logic and psycho-logic. PMID- 2882240 TI - Forgotten symptoms and primitive signs. PMID- 2882242 TI - Advice about milk for infants and young children. PMID- 2882241 TI - Eurohealth: Europe against cancer. PMID- 2882243 TI - Transient traumatic quadriplegia. PMID- 2882244 TI - Diagnosis and management of peritonitis in continuous ambulatory peritoneal dialysis. Report of a working party of the British Society for Antimicrobial Chemotherapy. PMID- 2882245 TI - The diagnosing mind. PMID- 2882246 TI - Inverse technology and medical education. PMID- 2882248 TI - Cancer near nuclear installations. PMID- 2882247 TI - Should travellers to Asia be vaccinated against Japanese encephalitis? PMID- 2882249 TI - Chernobyl and cancer epidemiology. PMID- 2882251 TI - Acupuncture and asthma. PMID- 2882250 TI - Epidural blood patch does not prevent headache after lumbar puncture. PMID- 2882252 TI - Fatal rhabdomyolysis in marathon runner. PMID- 2882253 TI - A sexist diagnosis. PMID- 2882254 TI - Cromoglycate for Cogan's syndrome. PMID- 2882255 TI - Variations in avoidable mortality and variations in health care. PMID- 2882256 TI - Breast cancer screening. PMID- 2882257 TI - Bed-nets and malaria suppression. PMID- 2882258 TI - Long-term results of prophylactic cefazolin versus placebo in total hip replacement. PMID- 2882259 TI - Tobacco chewer's pseudopalsy. PMID- 2882260 TI - Immune responses and allograft rejection. PMID- 2882261 TI - Dementia in Parkinson's disease. PMID- 2882262 TI - Wardrop-Landry-Guillain-Barre-Strohl. PMID- 2882263 TI - Tetrahydroaminoacridine and the central anticholinergic syndrome. PMID- 2882264 TI - Eicosapentaenoic acid in fat. PMID- 2882265 TI - Back pain and testicular germ cell tumours. PMID- 2882266 TI - Bodybuilder's psychosis. PMID- 2882267 TI - European medical exchanges: London/Utrecht. PMID- 2882268 TI - Shared records and patient care. PMID- 2882269 TI - Student numbers and manpower. PMID- 2882270 TI - Heart attacks and lowered blood pressure. PMID- 2882272 TI - Maintenance lithium. PMID- 2882271 TI - Everyday management of affective disorders. PMID- 2882273 TI - Pneumocystis carinii pneumonitis in adults with acute lymphoblastic leukaemia. PMID- 2882274 TI - Chorionic villus sampling followed by genetic amniocentesis and septic shock. PMID- 2882275 TI - Paroxysmal nocturnal haemoglobinuria and pregnancy. PMID- 2882276 TI - HIV-2 (West Germany, 1984) PMID- 2882277 TI - HIV-2 in UK. PMID- 2882278 TI - HIV-1 and HIV-2 infections in Italian AIDS/ARC patients. PMID- 2882279 TI - Methysergide and retroperitoneal fibrosis. PMID- 2882281 TI - Diagnosis of coronary heart disease. PMID- 2882280 TI - Colorectal cancer in spouses of colorectal cancer patients and controls. PMID- 2882282 TI - Subcutaneous infusion of apomorphine and lisuride in the treatment of parkinsonian on-off fluctuations. PMID- 2882283 TI - Convertible automobile touring and seasonal allergies. PMID- 2882284 TI - Deafness with enalapril and prescription event monitoring. PMID- 2882286 TI - Thallium and A Pale Horse. PMID- 2882285 TI - Sulindac and cough induced by converting enzyme inhibitors. PMID- 2882287 TI - Iatrogenic crime: criminal behaviour in patients receiving drug treatment. PMID- 2882288 TI - Effect of a single oral dose of prednisolone in acute childhood asthma. AB - 140 children of 184 with acute asthma entered a randomised double-blind trial of oral prednisolone (n = 67) compared with placebo (n = 73) administered soon after admission. The dose of prednisolone was 30 mg in children under 5, otherwise 60 mg. All children also received salbutamol. All had moderate or severe dyspnoea. Initial evaluation was similar for both groups. On reassessment after a few hours 20 children in the prednisolone group were fit for discharge compared with only 2 in the placebo group. There were no early reattendances. Children remaining in hospital had a shorter median duration of stay and were less likely to require further steroid therapy if they had initially received prednisolone. In acute asthma the prompt use of a single dose of oral prednisolone can reduce morbidity and the need for hospital care. PMID- 2882289 TI - Protection against severe rotavirus diarrhoea by rhesus rotavirus vaccine in Venezuelan infants. AB - The efficacy of the rhesus rotavirus vaccine candidate MMU-18006 was evaluated in a longitudinal double-blind field trial in Caracas, Venezuela. 247 infants aged 1 10 months were studied and followed for up to 1 year (201 completed the 1-year surveillance): 123 received a dose of 10(4) plaque-forming units of the vaccine orally and 124 received placebo. 21 episodes of rotavirus diarrhoea were detected, 16 in the controls and 5 in the vaccines: vaccine efficacy against any rotavirus diarrhoea was thus 68%. In the 1-5-month-old group the vaccine efficacy was 93%; only 1 episode of rotavirus diarrhoea was detected in 68 vaccinees and 15 such illnesses were observed in 65 controls (p less than 0.0001). For the entire study group vaccine efficacy was 100% against the most severe rotavirus diarrhoeal episodes. PMID- 2882290 TI - Cell-mediated immunity to a synthetic gliadin peptide resembling a sequence from adenovirus 12. AB - Cell-mediated immunity to a synthetic peptide, which has a 12-residue sequence from A-gliadin analogous to part of an early-region protein (Elb) from adenovirus 12, was investigated in patients with coeliac disease, healthy subjects, and disease controls by means of an indirect leucocyte-migration-inhibition assay. Patients with coeliac disease being treated with a gluten-free diet showed a significantly greater response than healthy subjects (p less than 0.001) or patients with inflammatory bowel disease. This cellular immune response was dependent on antigen concentration and was not present in untreated coeliac patients. PMID- 2882291 TI - T-cell inducers of suppressor lymphocytes control liver-directed autoreactivity. AB - The sensitisation of helper T cells of patients with autoimmune chronic active hepatitis to a liver-cell membrane-expressed asialoglycoprotein receptor protein is shown to be associated with a defect of T cells that specifically induce suppressor lymphocytes. These lymphocytes are found in an activated state in the peripheral blood of healthy people and may form part of an immunoregulatory network which actively prevents autoimmunity. PMID- 2882292 TI - Stroke risk in patients with carotid stenosis. AB - In 242 neurologically symptomless patients with at least one non-occlusive carotid stenosis on ultrasonography (continuous wave doppler and echotomography-B mode imaging) 171 carotids showed 0-50% stenosis, 150 showed 50-75% stenosis, and 78 showed more than 75% stenosis. The mean follow-up was 29.4 months, with stroke and death as end points. Of the 56 deaths 2 were causally linked to a stroke (crude annual mortality index 9.57%). Of the 10 strokes 7 were judged to be infarctions in carotid territory. 7 out of 20 patients with transient ischaemic attacks (TIA) had ischaemic symptoms definitely related to carotid territory. The crude annual indices of specific stroke or TIA were 0.45% for nonstenotic carotid, 0.23% for 0-50% stenosis, 2.48% for 50-75% stenosis, and 1.71% for 75 99% stenosis. Stenoses of greater than 50% were associated with more ischaemic events than were lesser degrees of narrowing (p less than 0.01). PMID- 2882293 TI - Mismatched double-stranded RNA (ampligen) reduces concentration of zidovudine (azidothymidine) required for in-vitro inhibition of human immunodeficiency virus. AB - 'Ampligen', a non-toxic, mismatched polymer of double-stranded RNA with antiviral and immunomodulatory activities reduced the concentration of zidovudine (azidothymidine, AZT; 'Retrovir', Wellcome) required for inhibitory activity against human immunodeficiency virus (HIV) in vitro. At the higher doses of AZT tested, the virustatic activity observed seemed to have a synergistic virustatic relation with ampligen. Thus, combined therapy with ampligen and AZT can be expected to be more beneficial than AZT alone to patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex since AZT regimens that seem to be clinically effective are associated with considerable toxicity. PMID- 2882295 TI - Portable unit for nursing infants in the prone position. PMID- 2882294 TI - Exacerbations of multiple sclerosis in patients treated with gamma interferon. AB - In an open, randomised study, 18 patients with clinically definite, relapsing remitting multiple sclerosis (MS) received 1 microgram, 30 micrograms, or 1000 micrograms doses of recombinant gamma interferon (IFN-gamma), given by intravenous infusion twice a week for four weeks. 7 patients had exacerbations during treatment. This exacerbation rate, compared retrospectively with the pretreatment rate and prospectively with the post-treatment rate, was significantly greater than expected. Exacerbations were not precipitated by fever or other dose-dependent side-effects. A concomitant increase in circulating monocytes bearing class II (HLA-DR) surface antigen suggested that the attacks induced during treatment were immunologically mediated. IFN-gamma is unsuitable for treatment of MS. PMID- 2882296 TI - Whither meta-analysis? PMID- 2882297 TI - Postgraduate and continuing education in need of orchestration. PMID- 2882298 TI - Beta-blockers and lipophilicity. PMID- 2882299 TI - Copper and the infant. PMID- 2882300 TI - Across-study evaluation of association between steroid dose and bolus steroids and avascular necrosis of bone. AB - Studies investigating steroid dose and avascular necrosis of bone (AVN) have found either a weak association or none at all. This quantitative review of published studies has evaluated the effects of steroid dose and bolus steroids on the risk of AVN. 22 papers with sufficient information for analysis were identified. The mean steroid dose for the cohort was plotted against the percentage in whom AVN developed. Total dose was divided into non-bolus (oral) and bolus dose, and doses 1, 3, 6, and 12 months after beginning steroids were tested separately for their association with AVN risk. There was a strong correlation between daily total dose and AVN rate (r = 0.61-0.80). Oral dose was strongly correlated with AVN rate (r = 0.70-0.86), but bolus dose was not associated with AVN risk. This strong association between AVN and steroid dose contrasts with the weak relations found in case-control studies from individual centres in which cases and controls received similar steroid regimens and therefore did not differ greatly in steroid dose. The method of deriving a single exposure level per study and comparing the amount of exposure across studies may be useful in assessing whether a drug's toxicity is dose dependent. PMID- 2882301 TI - Cholecystectomy and large bowel cancer. AB - The records of 5898 patients with colorectal cancer and 27,687 controls were examined for previous cholecystectomy. The estimated relative risks (and 95% confidence intervals) of development of any cancer of the large bowel and cancer of the right colon after cholecystectomy were 1.0 (0.8-1.2) and 1.1 (0.8-1.5) in women and 1.1 (0.9-1.5) and 1.2 (0.8-1.9) in men, respectively. Although these data do not rule out a small increase in risk, it is proposed that the association found in some other studies is, at least in part, an artifact. Intense diagnostic effort and treatment aimed at mild abdominal symptoms, encouraged by some patients and some medical care settings, could increase the detection and removal of gallstones and the early detection of colorectal cancer. PMID- 2882302 TI - Elective surgery for small abdominal aortic aneurysms. PMID- 2882303 TI - Surrogate testing for non-A, non-B hepatitis. PMID- 2882304 TI - Enhanced enzyme immunoassay for the detection of hepatitis B surface antigen. PMID- 2882305 TI - Oestrogen modulators and clear cell carcinoma of vagina. PMID- 2882307 TI - Malabsorption of cyclosporin in renal transplant recipient with Crohn's disease. PMID- 2882306 TI - Alpha-tocopherol in tardive dyskinesia. PMID- 2882309 TI - Caesarean section in Ireland and the USA. PMID- 2882308 TI - Myelosuppression after methotrexate, mitozantrone, and mitomycin C for treatment of advanced breast cancer. PMID- 2882310 TI - Light-chain isotype-associated B cell suppression in multiple myeloma. PMID- 2882311 TI - Successful births after ovum donation. PMID- 2882312 TI - Cyclosporin conversion in renal transplantation. PMID- 2882313 TI - Reporting obstetric ultrasound. PMID- 2882314 TI - Who should treat Hodgkin's disease? PMID- 2882315 TI - Sugar and health. PMID- 2882316 TI - Wernicke's encephalopathy in AIDS patient treated with zidovudine. PMID- 2882317 TI - HIV and HBV infection in drug abusers in Glasgow. PMID- 2882318 TI - Syringe exchange. PMID- 2882319 TI - AIDS and strongyloidiasis in Africa. PMID- 2882320 TI - Scintigraphic detection of rhabdomyosarcoma. PMID- 2882322 TI - Diabetics and renal failure. PMID- 2882321 TI - Screening for HIV antibody during pregnancy. PMID- 2882323 TI - Strict metabolic control and progression of incipient diabetic nephropathy. PMID- 2882324 TI - Systemic absorption from hydrocortisone foam enema in ulcerative colitis. PMID- 2882325 TI - Dural sinus thrombosis. PMID- 2882326 TI - Valproate inhibition of urea synthesis. PMID- 2882327 TI - Ventricular arrhythmias despite an apparently correctly placed Hickman-Broviac catheter. PMID- 2882328 TI - Sciatic-like referred pain after rubberband haemorrhoidal ligation. PMID- 2882329 TI - Alcohol and hypertension. PMID- 2882330 TI - Death associated with hyperventilation. PMID- 2882331 TI - Beta 2-microglobulin and haemodialysis. PMID- 2882332 TI - Carbimazole and breastfeeding. PMID- 2882333 TI - Safety of intravenous immunoglobulin. PMID- 2882334 TI - Release of atrial natriuretic peptide during pregnancy and immediate puerperium. PMID- 2882335 TI - Failure to detect multiresistant Escherichia coli in Bristol. PMID- 2882336 TI - Yersinia and iron. PMID- 2882337 TI - Trazodone/tryptophan for aggressive behaviour. PMID- 2882338 TI - More on the history of the ESR. PMID- 2882339 TI - Effectiveness of low-dose heparin in prevention of myocardial reinfarction. AB - 728 patients aged 50-75 years who had had Q-wave myocardial infarction 6-18 months previously were enrolled in a randomised, multicentre trial of low-dose heparin in prevention of reinfarction. The control group (365 patients) received their study centres' usual therapy; the heparin group (363 patients) also received subcutaneous calcium heparin (12,500 IU daily). Mean (SD) follow-up was 708 (265) days in the heparin group and 687 (251) in the control group. The reinfarction rate was 63% lower in the heparin than in the control group (4/303, 1.32% v 13/365, 3.56%). The difference in cumulative reinfarction rate between the groups was significant by both drug-efficacy (chi 2 = 3.99, p less than 0.05) and intention-to-treat analysis (chi 2 = 3.84, p = 0.05). Heparin treatment reduced the cumulative general mortality rates by 48% on drug-efficacy analysis (chi 2 = 3.88, p less than 0.05) and by 34% on intention-to-treat analysis (chi 2 = 2.05, not significant). Cardiovascular mortality was also reduced (33%) but not significantly. However, fatal events attributable to thromboembolism (fatal reinfarction, stroke, pulmonary embolism) were significantly less frequent in the heparin than in the control group (1 v 7, p less than 0.05). 60 patients (16.5%) discontinued heparin treatment, but only 23 patients (6.3%) stopped because of side-effects. Low-dose heparin appears to be effective, safe, well tolerated, and free from haemorrhagic risk for the prevention of myocardial reinfarction. PMID- 2882340 TI - Maternal oxygen therapy for intrauterine growth retardation. AB - Humidified oxygen (55%) was administered continuously through a face mask to 5 patients whose pregnancies (4 singleton and 1 twin) were all complicated by severe intrauterine growth retardation, oligohydramnios, high blood-flow impedance in the fetal aorta and umbilical artery, and low mean blood-velocity in the fetal thoracic aorta. All the fetuses were hypoxic and 2 were acidotic. After maternal hyperoxygenation, the fetal pO2 increased to within or near the normal range, and resulted in a sustained increase in the mean blood-velocity in the fetal thoracic aorta. 5 fetuses survived with minimum neonatal morbidity. The effect of maternal hyperoxygenation on the fetal pO2 in such cases may prove to be a useful method of assessing placental function and guiding management. PMID- 2882341 TI - Evidence for an immune response to HLA class I antigens in the vanishing-bileduct syndrome after liver transplantation. AB - The relation between donor and recipient status for HLA class I and II antigens in 62 patients undergoing liver transplantation was examined with particular reference to a well-defined variant of chronic rejection, the vanishing-bileduct (VBD) syndrome. A complete mismatch for class I antigens was more common in those with the VBD syndrome than in those with normal graft function or chronic graft malfunction unrelated to the syndrome (p less than 0.025). In contrast, a complete mismatch for class II antigens was considerably less common in those with the VBD syndrome than in those without (p less than 0.02). The association of a complete mismatch for class I and a partial or complete match for class II antigens with the VBD syndrome was highly significant (p less than 0.0005). These findings support the hypothesis that in the VBD syndrome both class I antigen expression on bileduct epithelium and immunological interaction at the level of class II antigens are required for the rejection process to occur. In addition, high-titre donor-specific antibodies to class I antigen, which were present in 6 of 14 of those with the VBD syndrome but in none of those without (p less than 0.0005), may be involved in the pathogenesis of bileduct damage. PMID- 2882342 TI - Neurological complications following liver transplantation. AB - 17 (33%) of 52 patients who underwent 56 consecutive orthotopic liver transplants had serious neurological complications postoperatively. The commonest complication was fits, which occurred in 13 (25%) patients. 50% of patients had their onset of fits within the first week. In 3 patients the fits were associated with postoperative metabolic encephalopathy and fatal progressive neurological deterioration. In some patients the evidence implicating cyclosporin in the development of fits is strong. In others factors such as electrolyte disturbances, steroid treatment for graft rejection, and cerebral infarction may have contributed to the development of the fits. Phenytoin controlled the fits in 10 out of 13 patients. Other neurological complications included 1 case of central pontine myelinolysis, 1 of cerebral abscess, and 4 of non-encephalopathic psychosis. PMID- 2882343 TI - Is cancer a macrophage-mediated autoaggressive disease? AB - As part of their physiological functions macrophages secrete various products that influence tissue environment. They can also secrete tumour growth promoting substances and it is highly probable that they help to establish tumour supporting fibrovascular stroma. Macrophages may fuse with other cells (including neoplastic cells) and many malignant properties of these hybrids or of their progeny may be maintained by the macrophage genome. In addition processes that occur after fusion might be important in inducing malignant transformation, especially when fusion has occurred with initiated cells. Superficial spreading melanoma is an example that is in keeping with the hypothesis of cell fusion. PMID- 2882344 TI - Another clinical test for congenital dislocation of the hip. PMID- 2882346 TI - Non-convulsive status epilepticus. PMID- 2882347 TI - Non-specific chest pain. PMID- 2882348 TI - Is there a place for hysteroscopy in prenatal and intrapartum diagnosis? PMID- 2882345 TI - Zidovudine (AZT) PMID- 2882349 TI - Clinical electrophysiology can pinpoint pathology in the visual pathway. PMID- 2882350 TI - Postpartum thyroiditis. PMID- 2882351 TI - Prognosis in the irritable bowel syndrome: a 5-year prospective study. AB - To establish the short-term and long-term results of current treatment of irritable bowel syndrome (IBS), 104 patients were studied prospectively. All patients were treated similarly and the results were assessed after a few weeks and then after at least 5 years. IBS can be diagnosed more easily than has been suggested--72% of this series were correctly diagnosed by their referring doctor, and only 12% required radiological studies to exclude organic disease. The response to treatment was considerably better than expected, possibly because of the more aggressive use of high-fibre diets and bulking agents. Thus, 85% of patients were rendered virtually symptom-free in the short term, and 68% were still virtually symptom-free 5 years later. The response to treatment was better in men than in women, in those with constipation than with diarrhoea, when the symptoms had initially been triggered by an episode of acute diarrhoea, and in patients with a relatively short history. With a few simple investigations, sympathetic explanation, and appropriate treatment, most patients with IBS have a good prognosis. PMID- 2882352 TI - Association of Metsovo lung and pleural mesothelioma with exposure to tremolite containing whitewash. AB - Pleural thickening, bilateral pleural hyalinised plaques, and restrictive lung function are found among inhabitants of four small villages in northwestern Greece. Transbronchial biopsy samples from patients with disease contained tremolite fibres. Malignant pleural mesothelioma has now been reported in these villages and accounts for approximately 1% of the total mortality from 1981 to 1985. The principal whitewash once used in this area is predominantly asbestiform tremolite. The fibre is identical in every respect to fibres found in the lung tissues of people with Metsovo lung. The membrane activity of this tremolite is greater than that of the commercially used asbestiform amphiboles amosite and crocidolite. This measure of cytotoxicity lends further support to the hypothesis that this fibre is the agent of Metsovo lung and mesothelioma. PMID- 2882353 TI - Reduction of redundant hospital stay through controlled intervention. AB - With the aim of reducing redundant hospital stay through controlled intervention, preset criteria for inpatient care were applied on a medical ward. The proportion of unjustified hospital stay days fell by 52.6% and the average length of stay on the experimental ward declined from 6.3 days to 4.6 days. On a control medical ward there was practically no change. At one-month follow-up, patients from the two wards did not differ in death rate, readmission rate, or subjective evaluation of health status. PMID- 2882354 TI - Possible role of pestiviruses in microcephaly. PMID- 2882355 TI - Influenza vaccination with adjuvant RU41740 in the elderly. PMID- 2882356 TI - Giardia and Cryptosporidium in drinking water. PMID- 2882357 TI - Excretion of atypical oocysts by patients with cryptosporidiosis. PMID- 2882358 TI - Reduction of ectopic pregnancy by injection under ultrasound control. PMID- 2882359 TI - Sphygmomanometer bladder length. PMID- 2882360 TI - Skull X-rays after head injury. PMID- 2882361 TI - Persistent gallbladder carriage of Salmonella typhi. PMID- 2882362 TI - Horse reservoir for Borrelia burgdorferi? PMID- 2882364 TI - Buccal and topical nitroglycerin. PMID- 2882363 TI - Sepsis and indomethacin failure in premature infants with symptomatic patent ductus arteriosus. PMID- 2882365 TI - Fine-catheter aspiration cytology and the acute abdomen. PMID- 2882366 TI - New radiological manifestation of Texidor's twinge. PMID- 2882367 TI - Dopamine receptor asymmetry in schizophrenia. PMID- 2882368 TI - Clinical pharmacology and geriatrics. PMID- 2882369 TI - Monitoring drug advertisements. PMID- 2882370 TI - Medical care for the homeless. PMID- 2882371 TI - Abdominal deliveries in Third World. PMID- 2882372 TI - Journals. PMID- 2882373 TI - Screening for breast cancer. PMID- 2882374 TI - Bran. PMID- 2882375 TI - HIV and onset of schizophrenia. PMID- 2882376 TI - Changes in sexual behaviour and incidence of gonorrhoea. PMID- 2882378 TI - HIV transmission and skin grafts. PMID- 2882377 TI - Digoxin-like immunoreactive substances in the perinatal period. PMID- 2882379 TI - Olive oil and coronary heart disease. PMID- 2882380 TI - Portal vein gas and sepsis after administration of OKT3. PMID- 2882381 TI - Safety of liver biopsy. PMID- 2882382 TI - Cardiac parasympathetic impairment in gastrointestinal Chagas' disease. PMID- 2882383 TI - Mass proguanil prophylaxis. PMID- 2882384 TI - Human papillomavirus and cervical cancer. PMID- 2882385 TI - Ifosfamide/mesna encephalopathy. PMID- 2882386 TI - Serum octadeca-9-11 dienoic acid concentrations in primary biliary cirrhosis. PMID- 2882387 TI - Angio-oedema and monosodium glutamate. PMID- 2882388 TI - Dengue-specific IgM and dengue haemorrhagic fever/shock. PMID- 2882389 TI - [Epidemiology, etiology and prognosis of liver cirrhosis. Studies on a selected patient sample of 356 patients (1970-1979)]. PMID- 2882390 TI - [Primary liver cell carcinoma]. PMID- 2882391 TI - [Drug dependence and suicide. Studies using forensic medicine records and patient histories]. PMID- 2882393 TI - [Suicide in psychological shock. Problems of forensic life insurance assessment of sudden suicides]. PMID- 2882392 TI - [Autoimmune liver diseases. Diagnosis, prognosis and therapy]. PMID- 2882394 TI - [Fatal peroral poisoning by morphine. Post-traumatic suicide or accident in chronic drug abuse]. PMID- 2882395 TI - Beta-adrenergic ([3H] CGP-12177) receptors are elevated in slices of soleus muscle from CHE 147 dystrophic hamsters. AB - We have utilized a muscle slice technique to compare the ontogeny of cell surface beta-adrenergic receptor binding in soleus and extensor digitorum longus (EDL) muscles of male Golden Syrian (GS) and Canadian Hybrid Farms 147 (CHF 147) dystrophic hamsters. Binding of the beta-adrenergic antagonist, [3H] CGP-12177 (CGP), to GS muscle slices was reversible, saturable, stereospecific and of high affinity. Bmax was higher in the soleus (2.57 +/- .12 fmol/mg wet wt) than in the EDL (1.6 +/- .17 fmol/mg wet wt) of adult animals while affinities were similar (0.35 +/- .06 and 0.24 +/- .04 nM respectively). No differences in binding characteristics were seen in EDL of GS compared to CHF 147 animals. In soleus slices frm GS hamsters, Bmax was highest at 16 days of age (5.72 +/- 0.26 fmol/mg), decreased between 16 and 29 days and remained constant until 300 days (2.51 +/- 0.52 fmol/mg). In dystrophic soleus slices, Bmax was also higher at 16 days than at any other age but receptor number decreased gradually, remaining higher than in GS until 90 days of age (p less than 0.05). The failure of beta adrenergic receptor number to decrease at a normal rate may be implicated in the pathogenesis of hamster polymyopathy. PMID- 2882396 TI - Age related changes of N-acetyl-beta-D-glucosaminidase and L-alanine aminopeptidase in mouse kidney, urine and plasma. AB - Age and sex dependent differences of N-acetyl-beta-D-glucosaminidase (NAG) and L alanine aminopeptidase (AAP) activities in kidney, urine and plasma of male and female mice were studied. The sex difference in NAG activity appeared between 27 and 38 days of age with the manifestation of significant differences in body weight and kidney growth. NAG activity in male kidneys was 3-fold that in females and its urinary level in mature males was over 10-fold higher. Androgenic regulation was found not only in the NAG contents in the kidneys and in the urinary excretion but also in the plasma NAG level, which showed higher in females. On the other hand, AAP activity in kidney, urine and plasma did not show much sex differences. Age related changes in AAP activity were not found except in the kidney and marked androgenic regulation was also not found in AAP. These results indicate that NAG and AAP, which are both urinary enzymes used as indicators of renal lesions, may be regulated differently. PMID- 2882397 TI - Stimulation of dopamine synthesis and activation of tyrosine hydroxylase by phorbol diesters in rat striatum. AB - In rat striatal synaptosomes, 4 beta-phorbol 12-myristate 13-acetate (PMA) and 4 beta-phorbol 12,13-dibutyrate (PDBu), two activators of Ca2+-phospholipid dependent protein kinase (protein kinase C) increased dopamine (DA) synthesis measured by following the release of 14CO2 from L-[1-14C] tyrosine. Maximal stimulation (21-28% increase of basal rate) was produced by 0.5 microM PMA and 1 microM PDBu. 4 beta-Phorbol and 4 beta-phorbol 13-acetate, which are not activators of protein kinase C, were ineffective at 1 microM. PMA did not change the release of 14CO2 from L-[1-14C]DOPA. Addition of 1 mM EGTA to a Ca2+-free incubation medium failed to affect PMA stimulation. KC1 (60 mM) enhanced DA synthesis by 25%. Exposure of synaptosomes to either PMA or PDBu prior to KC1 addition resulted in a more than additive increase (80-100%) of DA synthesis. A similar synergistic effect was observed when the phorbol diesters were combined with either veratridine or d-amphetamine but not with forskolin and dibutyryl cyclic AMP. Pretreatment of striatal synaptosomes with phorbol diesters produced an activation on of tyrosine hydroxylase (TH) associated with a 60% increase of the Vmax and a decrease of the Km for the pterine cofactor 6-methyl-5,6,7,8 tetrahydropterin. These results indicate that protein kinase C participates in the regulation of striatal TH in situ and that its activation may act synergistically with DA releasing agents in stimulating DA synthesis. PMID- 2882398 TI - Phorbol 12,13-dibutyrate enhances electrically stimulated neuromessenger release from rat dorsal hippocampal slices in vitro. AB - The protein kinase C activator 4 beta-phorbol 12,13-dibutyrate (PDB) enhanced the electrically stimulated release of radiolabelled noradrenaline (NA), acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) from dorsal hippocampal slices of the rat in vitro in a concentration-dependent manner. 4 alpha-Phorbol 12,13 didecanoate did not have an effect on the electrically stimulated release of any of the neuromessengers. Carbachol, which when present in the superfusion medium alone inhibited [14C]ACh release, significantly reduced the effect of PDB on the release of this neuromessenger. In the presence of either clonidine or [Leu5]enkephalin, which by themselves inhibited the electrically stimulated release of [3H]NA, the effect of PDB was significantly reduced. The enhancing effects of yohimbine and PDB on the electrically stimulated release of [3H]NA were additive. In all three cases, thus, the net effects of PDB were of a similar magnitude, whether the various compounds were present or not. Taken together, the present data suggest that the diacylglycerol/protein kinase C pathway is involved in the stimulus-evoked release of NA, ACh and 5-HT from dorsal hippocampal nerve terminals. Protein kinase C seems not to be involved in the modulation of the release of NA via presynaptic alpha 2-adrenoceptors and delta-opioid receptors and in that of ACh via presynaptic ACh receptors in that brain region. PMID- 2882399 TI - Binaltorphimine and nor-binaltorphimine, potent and selective kappa-opioid receptor antagonists. AB - The opioid antagonist activities of two bivalent ligands, BNI and nor-BNI, have been evaluated in smooth muscle preparations and in mice. Both ligands are highly potent and selective as kappa opioid receptor antagonists, with relatively feeble blocking activity at mu and delta opioid receptors. BNI and nor-BNI represent the first highly selective kappa opioid receptor antagonists and should be of great utility as molecular probes for identifying the interaction of agonist ligands with kappa opioid receptors in vitro and in vivo. PMID- 2882400 TI - Association between the behavioral and neurochemical effects of amphetamine: hemispheric asymmetry study. AB - Effects of amphetamine on concentrations of dopamine, norepinephrine and serotonin in several monoamine-containing cell body and terminal regions were examined left and right separately in rats. Results suggest that amphetamine reduced the L-R asymmetry of most of these measures, and this effect is more significant in the cell body than in the terminal regions. Behaviorally, amphetamine also decreased L-R asymmetry of the spontaneous turning behavior in rats and this latter effect is most closely associated with the reductions of dopamine and norepinephrine asymmetries in the substantia nigra and reduction of norepinephrine asymmetry in the locus coeruleus. PMID- 2882401 TI - Effects of beta-chlornaltrexamine on food intake, body weight and opioid-induced feeding. AB - beta-Chlornaltrexamine (beta-CNA) is a non-equilibrium opioid receptor antagonist which alkylates and inactivates opioid receptors. Because opioid peptides are thought to contribute to the regulation of food intake, we examined the effects of intracerebroventricular (icv) injections of beta-CNA on the food intake and body weight of male rats. We also tested the ability of beta-CNA to block food intake stimulated by selective agonists of kappa, mu and delta opioid receptors: dynorphin A2 (DYN), Tyr-D-Ala-Gly-(Me)Phe-Gly-ol (DAGO), and [(D-Ser2,Leu5] enkephalin-Thr6 (DSLET). Treatment with beta-CNA caused a long-term (2-4 days) reduction in daily food intake and a concomitant reduction in body weight. An additional experiment indicated that the weight loss after beta-CNA treatment could be completely accounted for by the reduction in intake. beta-CNA treatment also abolished or greatly attenuated the feeding effects of DAGO, DSLET and DYN, even when these peptides were tested 26 hours after beta-CNA administration. The long duration of the effects of beta-CNA suggests that this compound will be a useful pharmacological tool in further study of the opioid feeding system. PMID- 2882403 TI - [The tasks of optometry offices]. PMID- 2882402 TI - Inhibitory effect of norepinephrine on immunoreactive corticotropin-releasing factor release from the rat hypothalamus in vitro. AB - Effects of catecholamines on immunoreactive corticotropin-releasing factor (I CRF) release from the rat hypothalamus were examined using a rat hypothalamic perifusion system and a rat CRF RIA in vitro. Norepinephrine had a potent inhibitory effect on I-CRF release in a dose-dependent manner at 0.1 nM-1 microM concentrations, but dopamine did not. This inhibitory effect of norepinephrine was completely blocked by propranolol, but only partially blocked by phentolamine. Isoproterenol also had a potent inhibitory effect at 0.01-100 nM concentrations, and a high dose of phenylephrine (10 nM) inhibited I-CRF release. Clonidine did not influence I-CRF release. These results suggest that norepinephrine inhibits I-CRF release mainly through the beta-adrenergic receptor and partially through the alpha 1-receptor. PMID- 2882404 TI - Classical and late-onset forms of congenital adrenal hyperplasia caused by 21-OH deficiency reveal different alterations in the C4/21-OH gene region. AB - Congenital adrenal hyperplasia (CAH) is due to defective adrenal cortisol biosynthesis. In most cases, deficiency of a P 450-C21 specific steroid hydroxylase impairing cortisol synthesis has been found. The disease is HLA linked, and on clinical grounds it can be divided into two major forms, the classical and the non-classical type. Here, evidence is presented that the classical and the non-classical forms of CAH caused by 21-OH deficiency are due to different genetic alterations in the C4/21-OH gene region. In most cases of classical CAH associated with the HLA-Bw47 antigen, a specific and selective loss of the 21-OH B gene was observed with some interesting exceptions. Alterations in the 21-OH gene region in the non-classical forms of CAH, patients either HLA-B14; DR1 homo- or heterozygous, are different. Our data indicate the possibility of gene conversion events in this genomic region in non-classical CAH. PMID- 2882405 TI - Selective beta 1-adrenergic receptor-blockade with atenolol enhances growth hormone releasing hormone and mediated growth hormone release in man. AB - The growth hormone (GH) responses to a single bolus injection of the growth hormone releasing hormone (GRH) were examined in the basal state and in the presence of beta-adrenergic receptor blocking agents of different specificity in ten normal men. During a constant five-hour infusion of 56 micrograms/min of propranolol (nonselective beta-adrenergic receptor-blocker) in seven subjects studied, there was a significant augmentation of the GH release in response to exogenous GRH compared to the GH response during saline infusion, as measured by the peak serum GH concentrations after GRH (P = 0.019) and the integrated GH values (P = 0.019). A similar significant enhancement of GH responses to exogenous GRH as compared to the control day was observed with the specific beta 1-adrenergic receptor-blocker atenolol in all seven subjects studied (four of whom also participated in the propranolol study). Both the peak GH response to a GRH bolus and the integrated GH values were significantly greater with atenolol (P = 0.019 for both). There was no difference in serum GH concentrations after beta-adrenergic receptor-blocking drugs during a three-hour sampling period before GRH administration compared to placebo. Our results support the concept that beta-adrenergic receptors may modulate either the release or action of hypothalamic somatostatin in the control of GH secretion in man. We suggest the effect is mediated by specific beta 1-adrenergic receptors. PMID- 2882406 TI - Reduction of a metal or disulfide bond associated with the receptor: a general hypothesis for the mechanism of action of adrenergic agents. AB - Epinephrine and norepinephrine have been found to reduce Fe3+-heme to Fe2+-heme. Evaluation of the influence of these and structurally similar compounds on heme reduction and platelet aggregation led to the concept that epinephrine may exert its effects on platelets by first binding to a receptor and then reducing a nearby membrane heme group to transmit its agonist stimulus. Similar to alpha adrenergic agonists, we now report that beta agonists can reduce heme. Multiplying 1/kd for receptor binding for each agonist times the reduction of heme at 1.5 X 10(-4)M agonist gives a figure for each drug which closely parallels the potency of these drugs on beta 1 agonists (r = 0.994) and on beta 2 agonists (r = 0.853). Epinephrine and isoproterenol were also found to reduce heme in cytochrome c providing evidence that this mechanism could work well in an intact protein. The results are supportive of the hypothesis that all adrenergic agonists first bind to a membrane receptor and then reduce a heme or similar metal group to transmit the activating signal. PMID- 2882407 TI - Reduction of a disulfide bond by beta-adrenergic agonists: evidence in support of a general "reductive activation" hypothesis for the mechanism of action of adrenergic agents. AB - Beta-adrenergic agonists, but not antagonists, were found to reduce the disulfide bond of 5,5'-dithiobis-2-nitrobenzoic acid (DTNB). The extent of DTNB reduction was proportional to the intrinsic activity for these agonists. The results suggest a novel mechanism for transmission of the signal when a beta-adrenergic agonist occupies its receptor. We proposed that beta-adrenergic agonists exert their effects to activate the adenylate cyclase by reducing a disulfide bond in the receptor (R) or guanyl nucleotide binding protein (G) component of the adenylate cyclase complex leading to tight binding of GTP to G and activation of G. PMID- 2882408 TI - [Development of a prognostic index in Crohn disease]. PMID- 2882409 TI - Mechanisms of bacterial pathogenicity that involve production of calmodulin sensitive adenylate cyclases. PMID- 2882410 TI - Binding of two anthranilic acid derivatives to human albumin, erythrocytes, and lipoproteins: evidence for glafenic acid high affinity binding. AB - The binding of two anthranilic acid derivatives, glafenic and floctafenic acids, to human erythrocytes and plasma proteins has been investigated in vitro by equilibrium dialysis. Despite their close chemical structures it was shown that the binding of the two compounds to serum albumin, lipoproteins, and erythrocytes was dramatically different both in quality and quantity. Using various techniques including fluorometry and circular dichroism, it was shown that glafenic acid binds to the human serum albumin (HSA) warfarin/azapropazone site and that floctafenic acid binds to both warfarin/azapropazone and benzodiazepine sites. Glafenic acid is strongly bound to HSA with n = 1, k = 2.4 X 10(6) liters/mol and to erythrocytes with N = 12.4 mumol/liter, K = 1.7 X 10(6) liters/mol. Floctafenic acid is bound with a weaker affinity to HSA, n = 2, k = 0.3 X 10(6) liters/mol and to erythrocytes, N = 2900 mumol/liter and K = 0.007 X 10(6) liters/mol. PMID- 2882411 TI - Accumulation of adenosine 3',5'-monophosphate in slices of rat cerebral cortex induced by alpha-adrenergic agonists. I. Responses to methoxamine and norepinephrine in adult and neonatal tissue. AB - The effects of adrenergic agonists and adenosine on the accumulation of adenosine 3',5'-monophosphate (cyclic AMP) were examined in cerebral cortical slices from adult and neonatal rats. Methoxamine (10 to 100 microM) produced up to a two-fold increase in tissue from adult animals only in the presence of optimal concentrations of adenosine (40 to 100 microM), but had no effect in neonatal tissue. Such responses were inhibited more readily by prazosin than by yohimbine, but the reverse was true for responses to norepinephrine; when tested without the addition of adenosine, however, responses to norepinephrine were somewhat more sensitive to prazosin. Under the latter conditions, norepinephrine induced about twice as much increase in cyclic AMP as did isoproterenol in adult tissue. While always prevented by alpha-adrenergic antagonists, the greater efficacy of norepinephrine was eliminated by methylxanthines only in some instances, but never in tissue from animals known to be less than 60 days of age. At 11 to 15 days of age, responses to norepinephrine were more than fourfold those to isoproterenol, even in the presence of methylxanthines, and were completely suppressed by propranolol. Responses to isoproterenol were enhanced when tested in the presence of adenosine, especially in neonatal tissue. The results suggest that both endogenous adenosine and age-related phenomena may account for some of the discrepancies among earlier studies. Moreover, they indicate that several populations of alpha-adrenergic receptors may be involved in responses to adrenergic agonists in rat cerebral cortical tissue. PMID- 2882412 TI - Accumulation of adenosine 3',5'-monophosphate in slices of rat cerebral cortex induced by alpha-adrenergic agonists. II. Studies on mechanisms underlying the interaction with adenosine. AB - Incubation of slices of rat cerebral cortex with the calcium ionophore A23187 produced small increases in the accumulation of adenosine 3',5'-monophosphate (cyclic AMP). While low concentrations of Ca2+ ions (e.g., 200 microM) were sometimes necessary, the presence of adenosine (e.g., 50 microM) was essential; no effect of ionophore was observed when isoproterenol or isobutylmethylxanthine was substituted for adenosine. These results are consistent with the previously advanced hypothesis that stimulation of alpha-adrenergic receptors in this issue may cause calcium mobilization and thereby produce a calmodulin-mediated stimulation of adenylate cyclase. However, there is no apparent explanation for the requirement for adenosine. In addition, the possibility that additional mechanisms may be operating was suggested by experiments in which the incorporation of 3H-adenine into cyclic AMP was examined under steady-state conditions. While brief exposure to 3H-adenine after maximal adenosine- or isoproterenol-induced accumulations had been achieved led to small increases in the specific activity of cyclic AMP, the combination of norepinephrine and adenosine (plus propranolol) produced substantial decreases in the specific activity of cyclic AMP. Since the rate of incorporation of radioactivity did not keep pace with the expansion of the cyclic AMP pool, it is possible that norepinephrine also caused some reduction in the rate of cyclic AMP degradation under these conditions. Other interpretations of these results are discussed. PMID- 2882413 TI - Ontogeny of adenosine 3',5'-monophosphate metabolism in guinea pig cerebral cortex. II. Development of responses to L-glutamate in the presence of adenosine or histamine. AB - The effects of L-glutamate and other dicarboxylic amino acids on the accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in slices of cerebral cortex from strain 2 guinea pigs were examined using tissue from animals at 39 days gestation to 7 days after birth. Responses to glutamate were inhibited completely by adenosine deaminase or theophylline unless histamine was present. When tested in the presence of adenosine, glutamate increased cyclic AMP accumulation up to 10 fold at 39 days gestation; the response was maximal at 52 days gestation, and both the efficacy and potency of glutamate declined thereafter. While the effects of glutamate were smaller in the presence of histamine plus theophylline, the developmental pattern was similar to that in the presence of adenosine. The relative potencies of D-aspartate, kainate, and alpha-methyl-DL-glutamate were much greater in fetal than in adult tissue. Glutamic acid diethyl ester, N-acetyl glutamate or 2,3-diaminopropionate had no effect in fetal tissue either in the presence or absence of glutamate. Responses to glutamate in adult tissue were much more dependent upon the presence of calcium ions than were those in fetal tissue. It was concluded that responses to glutamate involve mechanisms that differ in fetal and adult tissue. PMID- 2882414 TI - Expression of mouse histone genes: transcription into 3' intergenic DNA and cryptic processing sites downstream from the 3' end of the H3 gene. AB - Introduction of the mouse histone H3.1 gene into tk- mouse L cells by cotransfection with the herpesvirus thymidine kinase gene resulted in the production of two mRNAs from the transfected gene, one with a normal 3' end and the other one with a longer 3'-untranslated region, ending at site X, which was poly(A)+. In contrast, the endogenous histone H3.1 gene only produced a single mRNA. The cryptic poly(A)+ site was only used when the histone H3.1 gene was transfected. To localize possible downstream cryptic processing sites, the hairpin loop at the end of the histone gene was deleted and the resulting deletions were introduced into L cells. Two major mRNAs were produced from this gene, one ending at site X and the major one ending at site Y, which was located 150 nucleotides before site X. Transcription extended downstream of site X efficiently in the endogenous gene, as judged by the extent of transcription of downstream sequences in isolated nuclei. Transcription extended downstream of site X in the transfected gene because the placement of a normal histone 3' end downstream of site X resulted in transcripts that ended at site X and longer transcripts that ended with the new histone 3' end. These results indicate that transcription may normally proceed a substantial distance past the hairpin loop (greater than 500 bases). The formation of the different 3' ends in these transfected genes was due to competition between different processing mechanisms. PMID- 2882415 TI - Tissue-specific regulation of avian glutamine synthetase expression during development and in response to glucocorticoid hormones. AB - We have isolated a glutamine synthetase cDNA clone derived from chicken retinal RNA. The clone detects a 3.2-kilobase RNA in chicken retina, liver, and brain, based on Northern blotting analysis. The dramatic developmental rise observed for the retinal enzyme, assayed as glutamyl transferase activity, is accompanied by a corresponding rise in this RNA. Injection of hydrocortisone 21-phosphate into the yolk sac of day 10 embryos produces an increase in retinal glutamine synthetase mRNA and glutamyl transferase activity, assayed 4 days after injection. An increase in glutamine synthetase mRNA is also observed within 2 h of incubation of retinal organ cultures with hydrocortisone. Moreover, incubation of these cultures with cycloheximide at a concentration that inhibits protein synthesis by 93% affects neither the basal level nor the hydrocortisone-mediated induction of glutamine synthetase mRNA. Although expression of this RNA is developmentally regulated in the brain, steroid hormone injection does not result in a substantial induction. Hepatic glutamine synthetase mRNA is expressed constitutively between embryonic day 10 and 6 days after hatching and is also not hormone inducible. Southern blotting data with chicken DNA digested with EcoRI, HindIII, and BamHI are best interpreted in terms of the cDNA clone detecting only one gene. If so, several cell-type-specific regulatory mechanisms must function to modulate expression of this gene during development. PMID- 2882418 TI - Genetic linkage in neurologic diseases. PMID- 2882416 TI - Translational control of ribosomal protein synthesis during early Dictyostelium discoideum development. AB - Throughout the developmental program of Dictyostelium discoideum there are substantial changes in the rates of both ribosome utilization and rRNA transcription and processing. We examined the regulation of ribosomal protein (r protein) gene expression and found that, at the start of development, expression of these genes was drastically and specifically reduced by a block to translational initiation. An apparently separate event signals a sudden decrease in the relative amount of r-protein mRNA at about 10 h of development, a time when aggregated amoebae are forming tight cell-cell contacts. For the first 9 h of development, the relative amount of r-protein mRNA remained essentially unchanged and comparable to levels detected in growing cells. While the r-protein mRNAs were almost fully loaded on polysomes during vegetative growth, they were specifically excluded from polysomes at the start of development. The translational block was not the result of irreversible structural changes which inactivate the r-protein mRNAs since they remained translatable both in vitro, in wheat germ extracts, and in vivo, where they were recruited onto polysomes in the presence of the elongation inhibitor cycloheximide. In addition, precise measurements of poly(A) tail lengths on individual hybrid-selected mRNA species showed that there is no difference in the poly(A) tail length of r-protein mRNA isolated from growing cells and 1-h developing cells. Therefore, changes in translational efficiency cannot be attributed to cleavage of poly(A) tails. PMID- 2882419 TI - Fatal familial insomnia and dysautonomia. PMID- 2882417 TI - Molecular analysis of human muscular dystrophies. AB - The ability to map disease loci using restriction fragment length polymorphisms (RFLPs) identified by DNA probes has revolutionized molecular genetics. Duchenne and Becker muscular dystrophies have been shown to be localized within the same very small region of Xp21 on the human X chromosome. The mutation itself should soon be identified at the DNA level, which will permit a detailed analysis of the molecular defect at the biochemical level. Rapid progress has also been made in the study of myotonic dystrophy on chromosome 19. DNA markers closely linked to the mutant locus have been identified, making antenatal diagnosis possible in informative families. Autosomal recessive muscular dystrophies are more difficult to study, but the means to localize even these mutations is being developed. The next decade should prove to be an exciting one for those involved in the molecular analysis and clinical management of human muscular dystrophies. PMID- 2882420 TI - Comparison of medical and surgical treatment for unstable angina pectoris. Results of a Veterans Administration Cooperative Study. AB - We conducted a multicenter, randomized, prospective study comparing medical therapy alone with coronary-artery bypass surgery plus medical therapy in 468 men with unstable angina pectoris. Patients were entered in the study from June 1, 1976, to June 30, 1982. Among those assigned to surgery who received bypass grafts, operative mortality was 4.1 percent. Arteriography performed after one year of follow-up revealed that 74.8 percent of the grafts studied were patent. The cumulative rate of crossover from medical to surgical therapy after two years was 34 percent; the operative mortality among patients crossed over was 10.3 percent. Nonfatal myocardial infarction occurred in 11.7 percent of the patients treated surgically and 12.2 percent of those treated medically (no significant difference). Most of the nonfatal myocardial infarctions in the surgical group occurred in the perioperative period. Overall, the two-year survival rate computed by life-table analysis did not differ between the two groups. However, the curves reflecting mortality as a function of left ventricular ejection fraction were significantly different (P = 0.03); surgery was associated with a significantly reduced mortality among patients with lower ejection fractions. We conclude that patients with unstable angina pectoris have a similar outcome after two years whether they receive medical therapy alone or coronary bypass surgery plus medical therapy. However, patients with reduced left ventricular ejection fractions may have a better two-year survival rate after coronary bypass surgery. PMID- 2882421 TI - DNA replication: many strands converge. PMID- 2882422 TI - The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro. AB - Cell-free extracts prepared from human 293 cells, supplemented with purified SV40 large-T antigen, support replication of plasmids containing the SV40 origin of DNA replication. A cellular protein (Mr approximately 36,000) that is required for efficient SV40 DNA synthesis in vitro has been purified from these extracts. This protein is recognized by human autoantibodies and is identified as the cell cycle regulated protein known as proliferating cell nuclear antigen (PCNA) or cyclin. PMID- 2882423 TI - Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. AB - Identification of the cellular proteins whose expression is regulated during the cell cycle in normal cells is essential for understanding the mechanisms involved in the control of cell proliferation. A nuclear protein called cyclin of relative molecular mass 36,000 (Mr 36K), whose synthesis correlates with the proliferative state of the cell, has been identified in several cell types of human, mouse, hamster and avian origin. The rate of cyclin synthesis is very low in quiescent cells and increases several fold after serum stimulation shortly before DNA synthesis. Immunofluorescence and autoradiography studies have shown that the nuclear staining patterns of cyclin during S phase have a sequential order of appearance and a clear correlation can be found between DNA synthesis and cyclin positive nuclei. The proliferating cell nuclear antigen (PCNA) and cyclin have many common properties and it has been shown that these two are identical. Recently a protein which is required by DNA polymerase-delta for its catalytic activity with templates having low primer/template ratios has been isolated from calf thymus. We report here that cyclin and the auxiliary protein of DNA polymerase-delta are identical. PMID- 2882424 TI - Functional identity of proliferating cell nuclear antigen and a DNA polymerase delta auxiliary protein. AB - The mechanism of replication of the simian virus 40 (SV40) genome closely resembles that of cellular chromosomes, thereby providing an excellent model system for examining the enzymatic requirements for DNA replication. Only one viral gene product, the large tumour antigen (large-T antigen), is required for viral replication, so the majority of replication enzymes must be cellular. Indeed, a number of enzymatic activities associated with replication and the S phase of the cell cycle are induced upon SV40 infection. Cell-free extracts derived from human cells, when supplemented with immunopurified SV40 large-T antigen support efficient replication of plasmids that contain the SV40 origin of DNA replication. Using this system, a cellular protein of relative molecular mass 36,000 (Mr = 36K) that is required for the elongation stage of SV40 DNA replication in vitro has been purified and identified as a known cell-cycle regulated protein, alternatively called the proliferating cell nuclear antigen (PCNA) or cyclin. It was noticed that, in its physical characteristics, PCNA closely resembles a protein that regulates the activity of calf thymus DNA polymerase-delta. Here we show that PCNA and the polymerase-delta auxiliary protein have similar electrophoretic behaviour and are both recognized by anti PCNA human autoantibodies. More importantly, both proteins are functionally equivalent; they stimulate SV40 DNA replication in vitro and increase the processivity of calf thymus DNA polymerase-delta. These results implicate a novel animal cell DNA polymerase, DNA polymerase-delta, in the elongation stage of replicative DNA synthesis in vitro. PMID- 2882425 TI - Cell biology. Cyclins in meiosis and mitosis. PMID- 2882426 TI - Relationship between the nerve action potential and transmitter release from sympathetic postganglionic nerve terminals. AB - At the skeletal neuromuscular junction, electrophysiological methods have provided much useful information about the mechanisms involved in the release of transmitter. At the autonomic neuroeffector junction it has not been possible to carry out similar studies. Here we report a method of extracellular recording which allows simultaneous measurement of both the nerve action potential and transmitter release from postganglionic sympathetic nerve terminals. We have confirmed that release is intermittent, but the importance of this new approach is that the relationship between the nerve terminal action potential and transmitter release can be studied unambiguously for the first time. Thus we are able to show unequivocally that intermittence is caused by a low probability of release in the invaded varicosity and not by failure of the action potential to invade the varicosity. PMID- 2882427 TI - Activation of NMDA receptors blocks GABAergic inhibition in an in vitro model of epilepsy. AB - The application of tetanic electrical stimuli to the stratum radiatum fibre pathway in the hippocampus in vitro produces an NMDA (N-methyl-D-aspartate) receptor-dependent enhancement of synaptic efficacy. Repeated application of such stimuli produces a progressive enhancement of synaptic efficacy leading to the genesis of spontaneous and stimulation-evoked epileptiform discharges. We have used this in vitro approach to explore the cellular mechanisms which underlie the kindling model of epilepsy. Kindling of the stratum radiatum fibre pathway in vitro induced a progressive, long-lasting reduction of both spontaneous and stimulation-evoked GABAergic (gamma-aminobutyric acid-mediated) inhibitory postsynaptic potentials (i.p.s.ps). The reduction of i.p.s.ps by kindling was associated with a profound decrease in the sensitivity of CA1 pyramidal neurons to ionophoretically applied GABA and an increase in sensitivity to NMDA. The reduction of i.p.s.ps and GABA sensitivity was prevented by kindling in the presence of the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (D-APV). These results demonstrate that kindling-like stimulus patterns produce a reduction of GABAergic inhibition in the hippocampus resulting from a stimulus induced postsynaptic activation of NMDA receptors. The modulation of GABAergic inhibition by NMDA receptors may cause the synaptic plasticity which underlies the kindling model of epilepsy. PMID- 2882428 TI - A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics. AB - Catecholaminergic systems in discrete regions of the brain are thought to be important in affective psychoses, learning and memory, reinforcement and sleep wake cycle regulation. Tyrosine hydroxylase (TH) is the first enzyme in the pathway of catecholamine synthesis. Its importance is reflected in the diversity of the mechanisms that have been described which control its activity; TH levels vary both during development and as a function of the activity of the nervous system. Recently, we deduced the complete amino-acid sequence of rat TH from a complementary DNA clone encoding a functional enzyme. Here we demonstrate that, in man, TH molecules are encoded by at least three distinct messenger RNAs. The expression of these mRNAs varies in different parts of the nervous system. The sequence differences observed are confined to the 5' termini of the messengers and involve alternative splicing events. This variation has clear functional consequences for each putative form of the enzyme and could represent a novel means of regulating catecholamine levels in normal and pathological neurons. PMID- 2882429 TI - Differences between the neuronal handling of 3H-7- and 3H-7,8-(-)noradrenaline: implications for the release of the labelled neurotransmitter by nerve stimulation. AB - Neighbouring rabbit aortic strips were exposed to a tracer concentration of 3H-7- or 3H-7,8-(-)noradrenaline (bearing 30-35% of its label in position 8) and to 0.5 mumol/l unlabelled (-)noradrenaline for 60 min and then washed in amine-free Krebs solution. Catechol-O-methyl transferase and extraneuronal amine uptake were inhibited throughout. After 114 min of wash-out, the tissue contained less tritium when loaded with 3H-7-(-)noradrenaline than when loaded with 3H-7,8-( )noradrenaline, and the fractional rate of loss of tritium was greater for the former than for the latter tissues. In the presence of cocaine (to prevent neuronal re-uptake), the same percentage of tissue tritium was released by nerve stimulation (six consecutive periods of stimulation at 1 Hz for 5 min each) in spite of the above difference between tissue tritium levels of the two differently labelled amines. In the absence of cocaine, a higher percentage of tissue tritium was released by nerve stimulation (1 or 3 Hz, 5 min each) for 3H-7 than 3H-7,8-(-)noradrenaline. Unchanged 3H-(-)noradrenaline amounted to 35% of tritium in the stimulation-evoked overflow for 3H-7- and to 50% for 3H-7,8-( )noradrenaline (frequency of stimulation, 1 Hz). When monoamine oxidase (MAO) was inhibited, no differences were observed between the neuronal handling of 3H-7- and 3H-7,8-(-)noradrenaline, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882430 TI - [Drugs in migraine]. PMID- 2882431 TI - [Migraine: diagnosis, pathophysiology and therapy]. PMID- 2882432 TI - An integrative hypothesis concerning the pathogenesis and progression of Alzheimer's disease. AB - Observations, in Alzheimer's disease, in the pattern of nerve cell damage and loss, the pathology, microchemistry and immunology of senile plaques and neurofibrillary tangles and alterations in blood vessels are drawn together into a hypothesis that attempts to explain the pathogenesis and progression of the disorder. At the heart of this hypothesis lies a defect in blood brain barrier function and/or structure within the cerebral cortex and this defect may be the cause of the cerebral vessel amyloidosis common in many patients with Alzheimer's disease. Age-related alterations in blood brain barrier allow for damage to nerve terminals and limited formation of senile plaques within cerebral cortex; neurofibrillary tangles are formed within cortical and subcortical nerve cells which project to or near damaged vessels/senile plaques. Uptake of "neurotoxin" at affected terminals and retrograde transport to perikarya causes neurofibrillary tangles to be formed; their accumulation leads to perikaryal changes culminating in cell death and loss. Loss of cells in cortically projecting areas of subcortex such as nucleus basalis, locus caeruleus and dorsal raphe, which terminate on cerebral vessels, causes further blood brain barrier dysfunction, new plaque formation and continued cell loss in cortex and subcortex. Once started, such a process could be self-perpetuating and the initial site of damage could lie within the amygdala/hippocampus with putative pathogenic agent accessing the brain via the olfactory pathways. PMID- 2882433 TI - Commentaries: The nose, aluminosilicates and Alzheimer's disease. PMID- 2882434 TI - Hypophysectomy increases TYR-MIF-1-like immunoreactivity in rat plasma. AB - Complex interactions of the pituitary, hypothalamus, and pineal involving MIF-1 (Pro-Leu-Gly-NH2) were shown many years ago. One of the largest changes consisted of increased amounts of an MIF-1-like material in the plasma of hypophysectomized rats as measured by the skin lightening of darkened frogs. The present study used radioimmunoassay to measure immunoreactive Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) in intact, hypophysectomized, pinealectomized, and superior cervical ganglionectomized (SCG) rats. Samples were collected every 4 h for 24 h. Plasma concentrations of Tyr-MIF-1-like immunoreactivity were higher in hypophysectomized rats and lower in pinealectomized rats than in the intact or SCG groups, which were not reliably different from each other. In most groups, the highest plasma concentrations appeared to occur about 04.00 h, a time at which brain concentrations of Tyr-MIF-1-like immunoreactivity were low. However, no diurnal rhythm in plasma was seen in the pinealectomized rats. At none of the times did brain concentrations of immunoreactive peptide differ among the four groups. By high-performance liquid chromatography of plasma, the main peak of immunoreactivity was found to elute at the same position as Tyr-MIF-1, supporting the natural occurrence of this tetrapeptide. Thus, this study demonstrates that the concentration of immunoreactive Tyr-MIF-1 in plasma is increased by hypophysectomy. PMID- 2882435 TI - Dopaminergic and cholinergic influences on the growth hormone response to growth hormone-releasing hormone in man. AB - It is well established that compounds that modify dopaminergic and cholinergic activity in man may induce changes in circulating growth hormone (GH). We have, therefore, investigated the effect of a dopamine agonist, bromocriptine, and a dopamine antagonist, domperidone, as well as a muscarinic cholinergic antagonist, pirenzepine, on the GH response to an analogue of GH-releasing hormone (GHRH) in normal male subjects. GHRH(1-29)NH2 induced a rise in serum GH that was augmented by bromocriptine, antagonized by pirenzepine, but was unaltered by domperidone. As this dose of GHRH(1-29) NH2 has been shown to be maximally stimulatory to GH release, it is suggested that there are dopamine stimulatory and cholinergic inhibitory receptors to GH release independent of GHRH in man. PMID- 2882436 TI - Involvement of the locus coeruleus in the potentiation of the quipazine-induced head-twitch response by diazepam and beta-adrenoceptor agonists. AB - Head-twitching in rats induced by quipazine was reduced by bilateral lesions of the locus coeruleus (LC) produced by 6-hydroxydopamine. Both beta 1-and beta 2 adrenoceptor agonists potentiated the head-twitch induced by quipazine in sham operated controls. Lesions of the locus coeruleus increased the responses to the beta 1-adrenoceptor agonists, prenalterol and dobutamine, but reduced the response to the beta 2-adrenoceptor agonists, salbutamol and procaterol. Diazepam (0.25 mg/kg) also potentiated the response to quipazine and this was reversed to inhibition by lesions of the locus coeruleus. These results suggest that the beta 1-adrenoceptors involved are postsynaptic and the beta 2-adrenoceptors are presynaptic to neurones of the locus coeruleus and indicate a dual action of diazepam on the head-twitch induced by quipazine. Possible mechanisms for these effects are discussed. PMID- 2882437 TI - Effects of glutaminase inhibition on release of endogenous glutamic acid. AB - The effects of four inhibitors of glutamine hydrolysis on synaptosomes derived from several regions of the brain were studied. The calcium-specific release of endogenous glutamic acid was determined in the presence of varying concentrations of 6-diazo-5-oxo-norleucine (DON), N-ethyl-maleimide (NEM), 2-chloroadenosine (2 CA) or haloperidol. Both DON and NEM reduced the calcium-specific release in a concentration-dependent manner, equally in all regions tested. 2-Chloroadenosine also decreased release and the effect was most evident in the amygdala. As reported earlier, haloperidol blocked release of glutamic acid only in the amygdala. In synaptosomes from the amygdala, both DON and NEM failed to affect the calcium-specific release of aminobutyric acid (GABA), glycine or serotonin at concentrations which reduced release of glutamate by 50%; NEM, but not DON, elevated the release of dopamine. Dopamine itself affected neither the release of glutamate nor its blockade by haloperidol even in extremely large concentrations. PMID- 2882439 TI - Selective beta-antagonists are equally and highly potent at 5-HT sites in the rat hippocampus. AB - Serotonin (5-hydroxytryptamine, 5-HT) and various tryptamine-related drugs were equi-potent to known beta-antagonists in competition experiments of 125Iodo cyanopindolol binding in the rat hippocampus. IC50 values for all the tryptamine related drugs (5,7-DHT, 5-MT, 5-MEO, DMT) were very similar to those obtained for (-)-propranolol, (+/-)-cyanopindolol, zinterol and atenolol and were all in the nanomolar range. Saturation experiments demonstrated that in the rat hippocampus, a subpopulation of serotonin recognition sites comprised 50% of 125I-CYP binding. The KD was 140 +/- 30 pM and the Bmax was 71 +/- 7 fmole/mg protein. This suggests that 125I-CYP binding studies for the quantitation of beta-adrenergic receptors should be re-evaluated and caution should be exercised in the choice of the displacing agent for the definition of non-specific binding. (+/-) [125Iodo]cyanopindolol (I-CYP) has been used as a radioligand which binds with high affinity and specificity to beta-adrenoceptors (Engel, Hoyer, Berthold and Wagner, 1981). The reported low dissociation constant (27-40 pM) of 125I-CYP for beta-adrenoceptors in various tissues, in combination with its high specific radioactivity (2175 Ci mmole-1) allowed binding studies to be carried out with low protein and ligand concentrations. These factors have established 125I-CYP as the choice ligand for the quantitation of beta-adrenoceptors in our laboratory (Edwards and Henn, 1985).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882438 TI - Effects of dihydrokainic acid on extracellular amino acids and neuronal excitability in the in vivo rat hippocampus. AB - The effect of inhibition of the high-affinity uptake of glutamate on the extracellular concentration of amino acids and on neuronal excitability was studied in vivo in the hippocampus of the rat. The dentate gyrus or CA1 field were perfused through a dialytrode with Krebs-Ringer-bicarbonate or dihydrokainic acid solutions. The spontaneous electrical activity and evoked field potentials were recorded concomitantly at dendritic or somatic levels. The results showed that with dihydrokainic acid: the extracellular concentrations of both glutamate and taurine were markedly increased in both areas of the hippocampus, the response of taurine being greater in CA1, while other amino acids were unaffected; in the dentate gyrus, the field excitatory postsynaptic potential was decreased while the population spikes were augmented, indicating an increased excitability of the neuronal population. In CA1, both the excitatory postsynaptic potential and spikes were reduced in amplitude. These results indicate that changes in the extracellular concentration of endogenous glutamate influences excitability of the tissue and that inhibition of the uptake processes for putative amino acid neurotransmitters increases the postsynaptic action of synaptically-released endogenous amino acids. PMID- 2882440 TI - Effect of pentylenetetrazol-induced convulsions on somatostatin-like immunoreactivity in rat cerebrospinal fluid. AB - Somatostatin is a neuropeptide that in several experimental models of epilepsy has been suggested to modulate epileptic activity. The purpose of the present study was to investigate the role of somatostatin in seizure phenomena. We measured the somatostatin-like immunoreactivity (SLI) by radioimmunoassay of the cisternal CSF of rats. A polyethylene cannula had before-hand been inserted into the cisterna magna. Thereafter seizures were induced by pentylenetetrazol (PTZ). The nonconvulsive group of rats received a single subconvulsive dose of PTZ (30 mg/kg, i.p.). This group of rats exhibited only clonic jerks but not generalized clonic-tonic convulsion (GC). The CSF samples were taken 2 and 10 minutes after the jerks began. The convulsive group of rats received a single convulsive dose of PTZ (50 mg/kg, i.p.), and each of those animals had GC. From those rats the CSF samples were collected 5, 30, and 60 minutes and 4 and 24 h after the GC began. The values were compared with the SLI levels in controls, from which CSF was collected 10 minutes after injection of 0.9% NaCl. In the convulsion group the SLI levels increased 241% (p less than 0.01) five minutes after GC and returned to control level in 30 minutes. In the nonconvulsion group, where the rats expressed only jerks but not GC, SLI levels remained constant. These data suggest that somatostatin is released into CSF after the generalized clonic-tonic phase of the PTZ-induced convulsion. PMID- 2882441 TI - Pyroglutamate aminopeptidase activity in human cerebrospinal fluid decreases with age. AB - The activity of pyroglutamate aminopeptidase, the major enzyme catalyzing thyrotropin-releasing hormone (TRH) metabolism in human CSF, decreased with age. This decrement is not due to age-dependent appearance of any enzyme inhibitor in CSF. The results of these studies underline the importance of using age-matched controls in assessing abnormalities of TRH metabolism in CSF during disease states. PMID- 2882442 TI - Neuromediator sensitivity of neurons of reticular formation and orbital cortex in fasted and fed rabbits. PMID- 2882444 TI - Long-term potentiation in the dentate gyrus: induction and increased glutamate release are blocked by D(-)aminophosphonovalerate. AB - D(-)Aminophosphonovalerate, a specific antagonist of the N-methyl-D-aspartate subtype of glutamate receptor, was perfused through a push-pull cannula into the dentate gyrus of rats anaesthetized with urethan in order to observe its effect on the induction and maintenance of long-term potentiation and on the increase in release of endogenous glutamate associated with long-term potentiation. The amplitude of the population spike evoked by single test shocks to the perforant path was significantly depressed by 100 microM D(-)aminophosphonovalerate, but there was a minimal effect on the slope of the population excitatory postsynaptic potential, or on the concentration of glutamate released into the perfusate. A brief high-intensity tetanus given to the perforant path while D(-)aminophosphono valerate was being perfused failed to induce long-term potentiation or the sustained increase in glutamate release associated with long-term potentiation. Short-term post-tetanic potentiation was not affected. After wash-out of D( )aminophosphonovalerate, a second high-frequency train produced both long-term potentiation and an increase in glutamate release which was sustained for the subsequent 1 h period of observation. D(-)Aminophosphonovalerate did not suppress long-term potentiation once it had been induced. D(-)Aminophosphonovalerate (100 microM) did not itself affect in vivo release of glutamate. However, in a separate series of in vitro experiments, D(-)aminophosphonovalerate at concentrations of 50 microM and above was found to depress the Ca2+ -dependent, K+-stimulated release of preloaded [14C]-glutamate from dentate slices.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882443 TI - A detailed mapping of dopamine D-2 receptors in rat central nervous system by autoradiography with [125I]iodosulpride. AB - The benzamide derivative [125I]iodosulpride was used to generate light microscopic autoradiograms on sections of rat brain and spinal cord. Sites specifically labelled by [125I]iodosulpride over a low background correspond to dopamine D-2 receptors as shown by their pharmacology established by densitometric analysis of 11 typical areas from autoradiograms generated in the presence of five dopamine-competing agents. An atlas of D-2 receptors was established using 1 horizontal, 6 sagittal and 30 frontal sections, the latter serially prepared at 0.5-1 mm intervals. Labelled areas were identified by comparison with corresponding, classically stained sections. When their density, rated according to an arbitrary scale, was then compared to that previously reported for dopamine innervation, evaluated from distributional maps of dopamine histofluorescence or tyrosine hydroxylase immunoreactivity, three situations were found. In areas corresponding to cells of origin and established projection fields of the mesostriatal, mesolimbocortical, diencephalospinal and periglomerular systems the density of D-2 receptors generally paralleled that of dopamine innervation. D-2 receptors in substantia nigra (pars compacta or reticulata) and ventral tegmental area were strongly reduced after injections of the neurotoxin 6-hydroxydopamine into the medial forebrain bundle, suggesting their major localization on dendrites and perikarya of dopamine neurons. Most other described dopamine cell group areas also contained D-2 receptors. In contrast many areas without established dopamine innervation contained D-2 receptors, sometimes in high density. This was the case for large areas of the cerebral cortex (layers I-III and V-VI) outside the established projection fields of the mesocortical system, the cerebellum (moleculare layer and dense patches within lobule 9), the hippocampal formation (lacunosum moleculare layer), several septal, thalamic and hypothalamic nuclei, large tectal areas, numerous brainstem areas (including cranial nerve nuclei), etc. This situation might correspond to areas with minor and still undetected dopamine innervation or to a localization of D-2 receptors on cells (or cell parts) not receiving dopamine inputs. Finally several well-established dopaminergic areas did not reveal any D-2 receptor labelling. This was particularly the case in the hypothalamus (areas of origin or termination of the tuberohypophyseal and incertohypothalamic dopamine systems) but also in the hippocampal formation (alveus, fimbria, hilus dentate gyrus), amygdaloid complex (anterior, basolateral, medial nuclei).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2882446 TI - Region-specific loss of glutamate innervation in Alzheimer's disease. AB - Synaptosomal D-aspartate has been used as a marker for glutamate neurons in control and in postmortem Alzheimer's disease brains. This technique shows a marked (60%) decrease of the glutamate uptake site in cortical and hippocampal regions. There were no significant changes in subcortical regions. We interpret these results as indicating loss of, or damage to, cortical glutamatergic innervation. These losses probably represent the biochemical correlate of pyramidal neuron damage in Alzheimer's disease. PMID- 2882445 TI - Vasoactive intestinal polypeptide facilitates the late component of the 5 hydroxytryptamine-induced discharge in the cat superior cervical ganglion. AB - The intra-arterial administration of vasoactive intestinal polypeptide (VIP, 1-10 micrograms, i.a.) to the cat superior cervical ganglion facilitated or unmasked the late component but not the early component of the 5-hydroxytryptamine (5-HT, 0.5-50 micrograms, i.a.)-induced postganglionic discharge. The facilitation occurred in acutely and chronically decentralized ganglia. The early and late 5 HT discharges were blocked by MDL-72222, a 5-HT antagonist, but not by cholinergic antagonists. These data together with previous observations indicate that VIP selectively facilitates slow cholinergic and non-cholinergic excitatory mechanisms in autonomic ganglia. PMID- 2882447 TI - Excitatory amino acids increase glycogen phosphorylase activity in the rat spinal cord. AB - Glycogen phosphorylase is present in nervous tissue in an active and inactive form. Using a histochemical technique, an investigation into which putative neurotransmitters have the capacity to modify the activity of the enzyme, has been performed on the rat spinal cord. Intrathecal injections of L-glutamate and L-aspartate elevate glycogen phosphorylase activity in the dorsal horn, while substance P has no effect and only high doses of adenosine triphosphate (ATP) increase the enzyme activity. In addition the N-methyl-D-aspartate receptor antagonist, 5-amino-phosphonovaleric acid was found to block the elevation of glycogen phosphorylase activity in the dorsal horn produced by the peripheral activation of chemo-sensitive primary afferents. Excitatory amino-acid neurotransmitters can therefore, acting via second messengers and protein kinases, modify glycogen metabolism in the spinal cord. PMID- 2882448 TI - Subchronic haloperidol and sulpiride treatment induces region-specific changes in tissue levels of putative amino acid transmitters in rat brain. AB - The effect of 10 days treatment with haloperidol (0.5 or 2 mg/kg/day) or sulpiride (10 or 100 mg/kg/day) on regional brain tissue levels of GABA, glutamate, aspartate and glutamine was studied in the rat. The GABA levels were increased in the nucleus (nuc.) accumbens and striatum by haloperidol, but not by sulpiride. The glutamate and glutamine levels were increased in the nuc. accumbens by both drugs. The aspartate levels were increased in the nuc. accumbens by sulpiride. Tissue levels of all 4 amino acids studied remained unchanged in the substantia nigra following the drug treatment. These results indicate that dopaminergic activity has a region-specific influence on the utilization of aspartate, glutamate and GABA in rat brain. PMID- 2882449 TI - Neuroendocrine and sympathoadrenal response to anesthetics and related drugs. PMID- 2882450 TI - Biochemical mechanisms of developmental neurotoxicity of methylmercury. AB - Methylmercury has been designated a "behavioral teratogen" because of its ability to evoke abnormalities in the absence of gross morphological damage to the developing brain. Recent work indicates that exposure to doses of methylmercury associated with neurobehavioral actions causes early alterations in brain ornithine decarboxylase, an enzyme whose activity is related to the coordination of cellular maturation. These effects are followed by regionally-targeted perturbation of cell replication and differentiation, indicated by measurements of nucleic acid and protein synthesis and levels. Neurobehavioral disturbances are associated with postnatal alterations in synaptogenesis and synaptic activity, as exemplified by studies in catecholaminergic pathways. Thus, methylmercury alters neurotransmitter uptake and turnover in presynaptic terminals, as well as development of postsynaptic adrenergic receptor binding sites. These changes result in aberrant signal transmission across the synapse, with consequent effects on synaptic function and ultimately on the communication of trophic developmental signals which ordinarily pass from neuron to target tissue. Although the specific linkages among the various biochemical effects of developmental exposure to methylmercury remain to be elucidated, studies of this type can serve as a model with which to understand the subcellular mechanisms underlying behavioral teratogenesis. PMID- 2882452 TI - Giving meperidine for pain: should it be so mechanical? PMID- 2882451 TI - Slow-acting anti-rheumatic drug therapy for rheumatoid arthritis. AB - Rheumatoid arthritis is a disorder that frequently can be controlled with a program of physical therapy, rest and therapeutic doses of aspirin or another nonsteroidal anti-inflammatory medication. However, some patients' diseases are not controlled on this regimen. These patients are candidates for therapy with slow-acting anti-rheumatic drugs. This article discusses the indications for use of these medications as well as the potential benefits and adverse drug reactions commonly associated with their use. PMID- 2882453 TI - Synthesis of the Congress' work and future perspectives. PMID- 2882454 TI - Mitogenic factor for T inducer/helper cells in Entamoeba histolytica extracts. PMID- 2882455 TI - Clinical significance of determination of urinary proteins in epidemic hemorrhagic fever. PMID- 2882456 TI - Hereditary cataract. Perspective for prenatal screening. AB - The possibility that defects in lenticular proteins are one cause of hereditary cataract is discussed. Possible mutant loci for such proteins can be detected by linkage to restriction fragment length polymorphisms within or around these loci. In a family in which a Coppock cataract occurs, close linkage between the locus for this cataract and the gamma-crystallin gene cluster was found. The restriction fragment length polymorphism within the gamma-crystallin gene family is sufficiently informative to allow prenatal diagnosis of this disease within this family. PMID- 2882457 TI - A genetic linkage study of choroideremia. AB - One hundred and twenty-two members of 15 choroideremia families have been used in a genetic linkage study of choroideremia (TCD) using four DNA probes situated on the X chromosome. Linkage was analysed using DNA probes DXS14 (p58-1), DXYS1 (pDP 34), DXS178 (p212) and DXS177 (lambda 2.7). Statistically significant linkage was demonstrated with DXYS1 (theta = 0.00, lod 4.95), in agreement with the findings of Nussbaum et al. (1985). Evidence consistent with loose linkage to TCD was also found with DXS14 (theta = 0.31, lod 0.23), DXS178 (theta = 0.18, lod 1.41) and DXS177 (theta = 0.27, lod 0.20). The results suggest that TCD is located in the region Xq13-q21. Probe DXYS1 is likely to prove useful in the prenatal diagnosis of this condition. PMID- 2882458 TI - Choroideremia in interstitial deletion of the X chromosome. AB - An earlier reported family with a deletion of the proximal long arm of the X chromosome was reinvestigated with special attention to the presence of choroideremia. Two females were identified as carriers of choroideremia while a tapeto-retinal dystrophy was ascertained in a mentally retarded boy. RFLP analysis revealed that the interstitial deletion covered the locus DXYS1 and not DXS17. Chromosome studies indicated a deletion within the Xq21 area. PMID- 2882459 TI - Is written informed consent needed for antipsychotics? PMID- 2882460 TI - [Surgical aspects of hormone therapy in cryptorchism]. AB - 46 boys were sent for operation and have been treated primary with LH-RH nasal spray. Only 5 boys (10.9%) achieved permanent scrotal position. (Follow up time 15.8 months). Nevertheless we could see during hormonal treatment clinical improvement of testicular position in 46.8%. Partial mobilisation can improve the result of the operation. Enlargement of hypoplastic genitalia is a positive side effect of hormonal therapy. Poor results from hormonal therapy have boys with congenital anomalies as hypoplastic genitalia, intraabdominal or intracanalicular position of testis and combinations with other malformations. Better results from hormonal therapy have testes in a low position with normal developed external genitalia. PMID- 2882461 TI - Comparative inflammatory reactions in mice and hamsters to Entamoeba histolytica. PMID- 2882463 TI - [SIN-1 interactions with the generation of cyclic nucleotides and arachidonate oxide metabolites in the uterine muscle]. AB - In the uterine smooth muscle, SIN-1 stimulated cGMP accumulation independently of the presence of Ca2+ and activated the soluble form of guanylate-cyclase through mechanisms apparently similar to those involved in the stimulations evoked by NO containing compounds. These activations appear different from those induced by hydroperoxy-unsaturated fatty acids and which contribute to the carbachol mediated cGMP accumulation. SIN-1 did not influence the rise in cAMP of the biosynthesis of PG1(2) and 12-HETE due to exogenous arachidonic acid. By contrast, SIN-1 markedly inhibited the increased synthesis of PG1(2) induced by the ionophore A23187 which was due to a prior, Ca2+-dependent, liberation of endogenous arachidonic acid. The data suggests an interference of SIN-1 with the generation and/or the expression of the Ca2+ signal. PMID- 2882462 TI - [Comparison of the effects of SIN-1, sodium nitroprusside and nitrate derivatives on the inhibition of blood platelet aggregation and activation of soluble platelet guanylate-cyclase]. AB - We compared the effects of various nitrates, sodium nitroprusside (SNP), molsidomine, and its bioactive metabolite SIN-1, on platelet aggregation and on the activity of soluble guanylate-cyclase from human platelets. SIN-1 and SNP proved to be potent inhibitors of platelet aggregation and activated soluble guanylate-cyclase in contrast to nitrates and molsidomine which produced weak inhibition of aggregation and failed to activate soluble guanylate-cyclase. These results suggest a correlation between these products' inhibitory effect on aggregation and activation of guanylate-cyclase. PMID- 2882464 TI - [Pathophysiology of the nervous system]. PMID- 2882465 TI - Laboratory diagnosis of pertussis: the state of the art. PMID- 2882466 TI - Influence of isoproterenol on plasma immunoreactive atrial natriuretic peptide and plasma vasopressin in the anesthetized rabbit. AB - Changes in levels of plasma immunoreactive atrial natriuretic peptide (IR-ANP) were measured in response to administration of isoproterenol in the anesthetized, vagotomized rabbit. A dose-dependent increase in plasma IR-ANP was seen in response to 10 min isoproterenol infusions between 0.1 and 10.0 micrograms/kg/min. The time course of these responses showed the maximum levels of IR-ANP to be attained 10 min after the cessation of infusion. In rabbits in which plasma vasopressin (AVP) levels were also measured, the maximum levels of AVP were attained during the infusion period. There was no correlation between levels of AVP and IR-ANP suggesting that AVP released into the plasma did not affect directly the release of IR-ANP. The changes in IR-ANP in response to isoproterenol were significantly reduced in rabbits which had been administered the beta-1-adrenoceptor blocking agent, atenolol. In six rabbits in which the vagi remained intact, the increases in IR-ANP were reduced and became significant only with 10 micrograms/kg/min isoproterenol infusion. The results demonstrate that isoproterenol infusion increases the level of plasma IR-ANP in the anesthetized rabbit and suggest that this is through an effect on the heart rather than on peripheral vessels. PMID- 2882467 TI - Tight linkage of glnA and a putative regulatory gene in Rhizobium leguminosarum. AB - Rhizobium leguminosarum, biovar viceae, strain RCC1001 contains two glutamine synthetase activities, GSI and GSII. We report here the identification of glnA, the structural gene for GSI. A 2 kb fragment of DNA was shown to complement the Gln- phenotype of Klebsiella pneumoniae glnA mutant strains. DNA sequence analysis revealed an open reading frame (ORF) of 469 codons specifying a polypeptide of 52,040 daltons. Its deduced amino acid sequence was found to be highly homologous to other glutamine synthetase sequences. This ORF was expressed in Escherichia coli minicells and the corresponding polypeptide reacted with an antiserum raised against GSI. Upstream of glnA we found an ORF of 111 codons (ORF111) preceded by the consensus sequence for an ntrA-dependent promoter. Minicells experiments showed a protein band, with a molecular weight in good agreement with that (10,469) deduced from the nucleotide sequence. On the basis of homology studies we discuss the possibility that the product of ORF111 is equivalent to the PII protein of E. coli and plays a similar role in regulation of nitrogen metabolism. PMID- 2882468 TI - Correlation of the physical and genetic maps in the lin-12 region of Caenorhabditis elegans. AB - We describe the assembly of a set of overlapping clones from the lin-12 III chromosomal region that spans approximately 600 kb, and the identification of two restriction fragment length polymorphisms, eP6 and eP7, that flank the lin-12 locus. A comparison of the physical map and the genetic map yields approximate measurements of 930 kb/map unit for the eP6--lin-12 interval and 830 kb/map unit for the lin-12--eP7 interval. We interpret these values as supporting the proposal that the apparent clustering of genes observed for C. elegans autosomes results from decreased recombination frequency in clusters and not from nonrandom distribution of genes on the physical map. PMID- 2882470 TI - Bgl II polymorphic site upstream to the human complement component C4A gene. PMID- 2882471 TI - An anonymous single copy genomic probe (D8S9) (CW1) detects RFLP on chromosome 8. PMID- 2882469 TI - Identification and cell type specificity of the tyrosine hydroxylase gene promoter. AB - Genomic DNA encoding the rat tyrosine hydroxylase (TH) gene was isolated from a lambda phage library using a nick-translated fragment from a cDNA clone for rat TH. We have determined the initiation site for TH RNA synthesis and have sequenced 1100 bases of the primary transcript and 5' flanking region. The 5' end of the transcript is the same in several rat tissues in which TH is expressed as well as in rat pheochromocytoma cells (PC). RNA prepared from PC cells that had been stimulated with dexamethasone also mapped to the same transcription start site. Sequence upstream from the initiation site contains the canonical TATA box, but no apparent CAAT box. When a portion of the 5' flanking region of the TH gene (-773 to + 27) is fused to the chloramphenicol acetyltransferase (CAT) gene, it promotes expression of CAT in pheochromocytoma cells and GH4 cells, but not in two neural tumour lines, RT4-D and B103, nor in several non neural cell lines. This suggests that this region of the TH gene has features that confer tissue restricted expression on the TH promoter. PMID- 2882472 TI - A TaqI restriction fragment length polymorphism at the Hox-2.1 locus cosegregates with the Dlb-1 locus on mouse chromosome 11. PMID- 2882473 TI - Human cDNA probe (OL11) detects RFLP on chromosome 12 (D12S10). PMID- 2882475 TI - Frequent RFLP recognised by an anonymous sequence localised to 11q13 - q14 [D11S.3.7.(E79)]. PMID- 2882474 TI - Human cDNA probe (cCW147) detects RFLP on chromosome 5 (D5S9). PMID- 2882476 TI - Mapping of DNA markers close to the fragile site on the human X chromosome at Xq27.3. AB - We report the identification of a new RFLP detected by the DNA probe MN12, which is linked to both the fragile site on the X chromosome at Xq27.3 and the highly polymorphic locus detected by St14 (DXS52). In situ mapping confirms the localisation of MN12 distal to the fragile site. A detailed physical analysis of this region of the X chromosome using pulsed-field gel electrophoresis has shown that MN12, St14 and DX13 (DXS15) are physically linked within a region of 470kb. A long range restriction map around the MN12 locus reveals at least two candidate HTF islands, suggesting the existence of expressed sequences in this region. PMID- 2882477 TI - The complete nucleotide sequence of the glnALG operon of Escherichia coli K12. AB - The nucleotide sequence of the E. coli glnALG operon has been determined. The glnL (ntrB) and glnG (ntrC) genes present a high homology, at the nucleotide and aminoacid levels, with the corresponding genes of Klebsiella pneumoniae. The predicted aminoacid sequence for glutamine synthetase allowed us to locate some of the enzyme domains. The structure of this operon is discussed. PMID- 2882478 TI - The nucleotide sequence of the 5S ribosomal RNA of Actinia equina and Sepia officinalis. PMID- 2882480 TI - A single copy subclone, p1-101, from cosmid 3-3B, defines three RFLPs on 10pter q23 [HGM9 no. D10S4]. PMID- 2882479 TI - Human LDL receptor gene: two ApaLI RFLPs. PMID- 2882482 TI - Presence of a Hind III polymorphism in the J alpha region of the human TcR-alpha locus. PMID- 2882481 TI - Two RFLPs identified by an anonymous sequence (D7S19) (pTS119) from chromosome 7. PMID- 2882483 TI - A PvuII RFLP detected in the human prion protein (PrP) gene. PMID- 2882484 TI - Isolation of a polymorphic DNA sequence pJSB11 (D19S16) from the human chromosome 19cen-q13.2 region linked to the myotonic dystrophy (DM) gene. PMID- 2882485 TI - A locus at 19cen-19q13.2 (D19S15) containing three RFLPs linked to myotonic dystrophy (DM) is recognized by probe pJSB6. PMID- 2882486 TI - PstI RFLP in the human hexosaminidase (HEXB) gene on chromosome 5. PMID- 2882488 TI - Bgl II RFLP recognized by a human IRBP cDNA localized to chromosome 10. PMID- 2882487 TI - A BamHI RFLP at the Pim-1 locus on mouse chromosome 17. PMID- 2882489 TI - Molecular cloning and nucleotide sequence analysis of rat PCNA/cyclin cDNA. AB - The 'proliferating cell nuclear antigen' (PCNA), also known as cyclin, accumulates in the nuclei of dividing and transformed cells and reacts with autoantibodies from certain lupus patients. A full-length cDNA (1195 bp) clone encoding PCNA/cyclin was isolated from rat thymocyte cDNA library. The nucleotide sequence reveals an open reading frame of 783 nucleotides coding for 28.7 kD protein. The predicted amino acid sequence and composition are in excellent agreement with the published protein data of rabbit PCNA. We report the entire nucleotide sequence of the cDNA and complete amino acid sequence for rat PCNA/cyclin. PMID- 2882490 TI - A most primitive primodial gene as a building block of the genes for the adenylate kinase, F1-ATPase subunits (epsilon and gamma), aminoacyl-tRNA synthetase, and core enzyme subunits. AB - Internal homology units of F1-ATPase epsilon and gamma subunits were searched by computer-aided methods. The epsilon in E. coli (EC) and maize chloroplast (Ch1) was found to consist of three homologous domains, named domains I, II and III (amino acids 1-47, 48-95 and 96-139 for EC). The gamma in E. coli was demonstrated to have at least six homologous domains, tentatively named here domains I-III and V-VII (I = aa 1-23, II = 26-69, III = 71-112, V = 150-192, VI = 196-242, VII = 285-329), with leaving a region IV (113-149) unclassified. Adenylate kinases (AK's) in pig and E. coli were found to have three internal homology units, named I, I' and II (I = aa 1-47, I' = 48-79, II = 80-124 for pig). Statistical evaluations and dot matrix analyses at both base and amino acid sequence levels have confirmed that all of these repeating units, being about 46 amino acids long, are homologous with one another. Of these, epsilon III, II, gamma VII and AK II domains were most conservative and some of them showed homology to core enzyme alpha and an internal repeating unit of tryptophanyl-tRNA synthetase (Trp-RS). Thus these homology unit-encoding gene segments must be relics of a primodial gene. PMID- 2882491 TI - Circular dichroism analyses of tRNA X protein interactions. AB - The interactions of tRNA species with aminoacyl-tRNA synthetases and polypeptide chain elongation factor Tu from Thermus thermophilus HB8 were studied by the analyses mainly of the circular dichroism band of 2-thioribothymidine in position 54 of T. thermophilus tRNA species. PMID- 2882492 TI - Initial management of adolescent overdoses. AB - A retrospective study of pediatric patients presenting to a community hospital emergency department with acute intentional toxidromes was conducted. The characteristics of these patients and their initial medical management were reviewed. Forty-six patients were included in this study with 35 recreational overdoses and 11 suicide attempts or gestures. The mean age of these patients was 15.8 (range 10 to 18 years). The most commonly abused substance was ethanol, followed in frequency by benzodiazepines and barbiturates. Initial management centered on active airway management, gastrointestinal decontamination, and extended observation. Ten patients were intubated, lavaged, extubated, and subsequently discharged from the emergency department. Only one patient required hospital admission. The value of toxicologic screens, emergency department endotracheal intubations, gastric lavage, and charcoal/cathartic therapy is discussed. PMID- 2882493 TI - Inhibitory influences of MIF-1 (PLG) and Tyr-MIF-1 (YPLG) on aggression and defeat-induced analgesia in mice. AB - The effects of prolyl-leucyl-glycinamide (MIF-1, PLG), tyrosine-prolyl-leucyl glycinamide (Tyr-MIF-1, YPLG) and the exogenous opiate antagonist, naloxone, on aggressive interactions and defeat-induced analgesia were examined in male mice. All three substances reduced the number of bites required to obtain defeat in subordinate mice during aggressive encounters, as well as blocking subsequent defeat-induced analgesia. Tyr-MIF-1 had significantly greater inhibitory effects than MIF. These results suggest that both MIF and Tyr-MIF-1 may function as endogenous opioid antagonists and have inhibitory influences on aggression, with the antagonistic effects of Tyr-MIF-1 being more potent than those of MIF-1. PMID- 2882494 TI - Influence of centrally administered peptides on ear withdrawal from heat in the rabbit. AB - Certain neuropeptides previously linked to stress and implicated in CNS control of analgesia/algesia were tested using a recently developed analgesiometric model, the rabbit ear-withdrawal test. The latency to ear withdrawal increased in a dose-related manner after beta-endorphin was injected intracerebroventricularly (IVC). Intermediate doses (0.5 and 1.0 micrograms) of adrenocorticotropic hormone (ACTH) caused hyperalgesia as indicated by decreases in latency. Corticotropin releasing factor (CRF, 0.5 and 1.0 micrograms) also caused significant hyperalgesia late in the testing period. alpha-Melanocyte stimulating hormone (alpha-MSH, 0.25-2.0 micrograms), a molecule that shares the first 13 amino acid sequence with ACTH, and somatostatin (0.25-2.0 micrograms), caused no significant change in latency. However, 1.0 microgram doses of each peptide antagonized the analgesic effect of beta-endorphin (1.0 microgram) in the following order of potency: ACTH = alpha-MSH greater than CRF greater than somatostatin. The results support the idea that CNS peptides that are released during stress can exert opposing actions on acute pain, even though they may cause little effect alone. PMID- 2882495 TI - Characterization of pancreatic somatostatin binding sites with a 125I somatostatin 28 analog. AB - Somatostatin binding to guinea pig pancreatic acinar cell plasma membranes was characterized with an iodinated stable analog of somatostatin 28 (S28): 125I [Leu8,DTrp22,Tyr25]S28. The binding was highly dependent on calcium ions. In 0.2 mM free Ca2+ medium, binding at 37 degrees C was saturable, slowly reversible and exhibited a single class of high affinity binding sites (KD = 0.05 +/- 0.01 nM, Bmax = 157 +/- 33 fmol/mg protein). Dissociation of bound radioactivity occurred with biphasic kinetics. Rate of dissociation increased when dissociation was measured at a time before equilibrium binding was reached. In 30 nM free Ca2+ medium, binding affinity and maximal binding capacity were decreased by about 4 fold. Decreasing calcium concentrations increased the amount of rapidly dissociating form of the receptor. Somatostatin 14 antagonist, Des AA1,2[AzaAla4 5,DTrp8, Phe12-13]-somatostatin was active at the membrane level in inhibiting the binding. We conclude that using 125I-[Leu8,DTrp22,Tyr25]S28 as radioligand allows us to characterize a population of specific somatostatin receptors which are not different from those we previously described with the radioligand 125I [Tyr11]-somatostatin. Somatostatin receptors could exist in two interconvertible forms. Calcium ions are an essential component in the regulation of the conformational change of somatostatin receptors. PMID- 2882496 TI - Cutaneous changes associated with inflammatory bowel disease. AB - Inflammatory bowel disease often begins during adolescence, but may affect younger children. Associated skin lesions are not uncommon. Occasionally, cutaneous alterations may precede the onset of signs or symptoms of the gastrointestinal disorder. Erythema nodosum and pyoderma gangrenosum are the most common associated specific skin changes, but numerous others may be found. Although the skin condition often responds to treatment of the bowel, it may require additional therapy. PMID- 2882497 TI - [Pain and neuroregulators]. PMID- 2882498 TI - Postjunctional alpha-adrenoceptors in human superficial epigastric arteries and veins. AB - A pharmacological characterization of the postjunctional alpha-adrenoceptors in human superficial epigastric artery and vein was performed, using several alpha adrenoceptor subtype selective agonists, and the antagonists prazosin (alpha 1) and rauwolscine (alpha 2). In the arteries prazosin fulfilled the criteria for a competitive antagonism in concentrations 10(-9)-10(-7) M, giving a pA2-value of 9.17 in the Schild plot. Rauwolscine in concentrations 10(-8)-10(-6) M caused less pronounced but significant dextral shifts of the noradrenaline (NA) concentration-response curves. In the veins rauwolscine behaved like a competitive antagonist (10(-8)-10(-7) M). The pA2-value was 9.16. Prazosin 10(-9) M displaced the NA concentration-response curve, but higher concentrations (10( 8) and 10(-7) M) caused no further displacement. Prazosin reduced the Emax-values in the veins. In the arteries the rank order of potency for the agonists was: cirazoline (alpha 1) greater than NA greater than naphazoline (alpha 2) greater than guanfacine (alpha 2) greater than phenylephrine (alpha 1). The intrinsic activities of clonidine (alpha 2), ST 587 (alpha 1), B-HT 920 (alpha 2) and B-HT 933 (alpha 2) were too low to allow meaningful comparisons to be made. The rank order of potency in the veins was: NA greater than clonidine (alpha 2) greater than naphazoline (alpha 2) greater than guanfacine (alpha 2) greater than phenylephrine (alpha 1) greater than B-HT 920 (alpha 2) greater than cirazoline (alpha 1) greater than B-HT 933 (alpha 2). The intrinsic activity of ST 587 was low.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882499 TI - [Fetal alcoholism. A biological marker, gamma-glutamyltransferase]. PMID- 2882500 TI - [A case of pulmonary tuberculosis associated with periarteritis nodosa]. PMID- 2882501 TI - Effects of alpha 1- and alpha 2-adrenoceptor stimulation and blockade on plasma insulin levels in the mouse. AB - Stimulation of alpha-adrenoceptors is known to inhibit insulin secretion under a variety of conditions. In this study, the question of whether these alpha adrenoceptors are of the alpha 1- or the alpha 2-subtype was investigated in the mouse. The selective alpha 2-adrenoceptor agonist clonidine (0.05-50 nmol/kg) was found to markedly inhibit the insulin secretory response to both glucose and the cholinergic agonist carbachol. This inhibition of insulin secretion was counteracted by the alpha 2-adrenoceptor antagonist yohimbine (2.6 mumol/kg), but not by the alpha 1-adrenoceptor antagonist prazosin (2.6 mumol/kg). In contrast, the alpha 1-adrenoceptor agonist phenylephrine (0.05-50 nmol/kg) did not affect the insulin secretory response to either glucose or carbachol. Moreover, both yohimbine and prazosin increased basal plasma insulin levels. It is concluded that alpha 1- and alpha 2-adrenoceptor blockade is followed by enhancement of basal plasma insulin levels in the mouse, whereas alpha 2-adrenoceptor stimulation but not alpha 1-adrenoceptor stimulation impairs the insulin secretory response to glucose and carbachol. PMID- 2882502 TI - Effect of circulating somatostatin on exocrine pancreatic secretion in conscious dogs. AB - We determined the effects of exogenous somatostatin-14 (100 and 200 ng/kg/h; mimicking postprandial somatostatin concentrations) on pancreatic responses to a background infusion of secretion in combination with graded doses of CCK-8 in conscious dogs with chronic gastric and duodenal fistulas. The lower dose of somatostatin-14 (S-14), which produced S-14 plasma levels lower than measured after a meal, did not change basal or stimulated pancreatic secretion. The upper dose of S-14, which produced plasma S-14 concentrations slightly above the postprandial range, caused inhibition of pancreatic fluid and protein secretion to low doses of CCK-8 (p less than 0.05). The inhibition was surmountable with higher doses of CCK-8. We interpret these data as indicating that circulating S 14 is not an important hormonal regulator of exocrine pancreatic secretion. PMID- 2882504 TI - Effects of bethanechol on the pancreas in antrectomized and normal rats. AB - The effect of chronic administration of bethanechol and pentagastrin on the pancreas was examined. Rats were either antrectomized or subjected to a sham operation. Three weeks after surgery, rats received a daily intraperitoneal injection of either bethanechol (12 mg/kg) or pentagastrin (250 micrograms/kg) for 14 days. The fasting serum gastrin after bethanechol treatment increased to 1.89 times that of controls treated with saline. Although antrectomy decreased fasting serum gastrin to approximately 40% of controls, serum gastrin increased by 2.17 times that of the antrectomized rats and 1.37 times that of controls in the bethanechol group. After 14 days of bethanechol treatment, weight and amylase in the pancreas increased significantly compared with control; DNA and protein also increased 1.3 and 1.5 times that of control. The increase in DNA and pancreatic weight indicated that hyperplasia was the predominant mechanism. The pancreas showed atrophy in antrectomized rats but this was reversed by both bethanechol and pentagastrin. The results indicate that either endogenous gastric or extragastric gastrin release by cholinergic stimuli may have an important role in the regulation of pancreatic growth. PMID- 2882503 TI - Somatostatin analog-induced remission of necrolytic migratory erythema without changes in plasma glucagon concentration. AB - A 41-year-old woman with metastatic glucagonoma and the characteristic disabling rash, necrolytic migratory erythema, was treated with a synthetic somatostatin analog while waiting to undergo curative surgical resection. Plasma glucagon concentration (1,500-3,300 pg/ml, normal less than 200) remained elevated during analog therapy as the rash cleared. Only with surgical resection (partial pancreatectomy and partial hepatectomy) did glucagon levels return to normal. The therapeutic benefit caused by the analog in this syndrome differs from that in other endocrine tumor syndromes such as pancreatic cholera, carcinoid, or gastrinoma where circulating levels of tumor-produced agents are suppressed in conjunction with control of symptoms. PMID- 2882505 TI - Differential regulation of a Thy-1 gene in transgenic mice. AB - We have generated Thy-1.1-transgenic Thy-1.2 mice to study the developmental expression of the Thy-1 gene in detail by transcriptional and immunological methods. In brain, the expression of the injected gene was identical to that of the endogenous gene in a tissue- and development-specific manner. In lymphoid tissue, the transferred gene was also expressed correctly in the early phases of T-cell lineage development; however, as the T cells matured, the transcription of the transferred gene, but not the endogenous gene, was suppressed. This result shows that different regulatory elements are used to express the Thy-1 gene in early and late lymphoid development. PMID- 2882506 TI - Purification and subunit composition of atrial natriuretic peptide receptor. AB - A receptor for atrial natriuretic peptide (ANP) was purified 2700-fold, to apparent homogeneity, from cultured bovine aortic smooth muscle cells by affinity chromatography. The native ANP receptor has a molecular weight of 125,000 as determined by both metrizamide gradient centrifugation and nonreducing NaDodSO4/polyacrylamide gel electrophoresis. With 125I-labeled ANP as ligand, the purified receptor bound a maximum of 5.70 nmol of ligand per mg of protein and the dissociation constant was 4.0 X 10(-10)M. Upon treatment with 10 mM dithiothreitol, the purified receptor migrated as a single band at Mr 60,500 in NaDodSO4/polyacrylamide gel electrophoresis. These findings show that the holoreceptor for ANP in vascular tissue is composed of two subunits of identical apparent molecular weight, presumably linked by a disulfide bridge(s). PMID- 2882509 TI - Detailed ordering of markers localizing to the Xq26-Xqter region of the human X chromosome by the use of an interspecific Mus spretus mouse cross. AB - Five probes localizing to the Xq26-Xqter region of the human X chromosome have been genetically mapped on the mouse X chromosome using an interspecific cross involving Mus spretus to a contiguous region lying proximally to the Tabby (Ta) locus. Pedigree and recombinational analysis establish the marker order as being Hprt-FIX-c11-G6PD-St14-1. The size of this contiguous region is such that the X linked muscular dystrophy (mdx) mouse mutation probably maps within this segment. This in turn suggests that it is highly improbable that the mouse mdx locus represents a model for Duchenne muscular dystrophy (DMD). It is, however, compatible with the idea that this mutation may correspond in man to Emery Dreifuss muscular dystrophy. The high frequency of restriction fragment length polymorphisms found in this interspecific system for all the human cross-reacting probes examined up until now, using only a limited number of restriction enzymes, suggests that the Mus spretus mapping system may be of great potential value for establishing the linkage relationships existing in man when conserved chromosomal regions are concerned and human/mouse cross-reacting probes are available or can be obtained. PMID- 2882507 TI - Cloning and sequence of the human nuclear protein cyclin: homology with DNA binding proteins. AB - A full-length cDNA clone for the human nuclear protein cyclin has been isolated by using polyclonal antibodies and sequenced. The sequence predicts a protein of 261 amino acids (Mr 29,261) with a high content of acidic (41, aspartic and glutamic acids) versus basic (24, lysine and arginine) amino acids. The identity of the cDNA clone was confirmed by in vitro hybrid-arrested translation of cyclin mRNA. Blot-hybridization analysis of mouse 3T3 and human MOLT-4 cell RNA revealed a mRNA species of approximately the same size as the cDNA insert. Expression of cyclin mRNA was undetectable or very low in quiescent cells, increasing after 8 10 hr of serum stimulation. Inhibition of DNA synthesis by hydroxyurea in serum stimulated cells did not affect the increase in cyclin mRNA but inhibited 90% the expression of H3 mRNA. These results suggest that expression of cyclin and histone mRNAs are controlled by different mechanisms. A region of the cyclin sequence shows a significant homology with the putative DNA binding site of several proteins, specially with the transcriptional-regulator cAMP-binding protein of Escherichia coli, suggesting that cyclin could play a similar role in eukaryotic cells. PMID- 2882508 TI - A genetic analysis of extinction: trans-regulation of 16 liver-specific genes in hepatoma-fibroblast hybrid cells. AB - Hybrid cells formed by fusing different cell types generally fail to express the tissue-specific products of either parent, a phenomenon termed extinction. We have investigated the generality of this effect by assaying hepatoma-fibroblast hybrids for expression of 16 different liver-specific mRNAs. Fourteen of the mRNAs failed to accumulate in karyotypically complete hybrid clones, and quantitative measurements indicated that steady-state mRNA levels were depressed by a factor of at least 500-1000. However, all 14 liver-specific mRNAs were reexpressed in the hybrids following fibroblast chromosome loss. These data indicate that expression of whole sets of tissue-specific genes is affected in trans in intertypic hybrids and suggest that negative regulation of heterologous functions may be common form of gene control. PMID- 2882511 TI - Restriction fragment length polymorphism of the HLA-DP subregion and correlations to HLA-DP phenotypes. AB - The restriction fragment length polymorphism (RFLP) of the class II HLA-DP subregion of the major histocompatibility complex (MHC) of humans has been unraveled by Southern blotting using DP alpha and DP beta probes in a study of 46 unrelated individuals with known HLA-DP types. Contrary to earlier preliminary findings with a limited number of enzymes, the RFLP appears to be quite extensive both with the DP beta (14 different DNA markers defined by individual fragments or clusters thereof) and the DP alpha (8 markers) probes, especially when enzymes recognizing only four base pairs were used. A few markers were absolutely or strongly associated with individual DP antigens, whereas most were associated with two or more DP antigens as defined by primed lymphocyte typing. Thus, Southern blotting seems feasible for typing for most DP determinants by specific fragments or subtraction between the various more broadly reactive DNA markers, and the RFLP provides further information on the DP subregion in addition to that provided by primed lymphocyte typing. In two recombinant families, the DP beta and DP alpha DNA markers segregated with DP antigens, whereas the DR beta, DQ beta, DQ alpha, and DX alpha markers followed the DR and DQ antigens. PMID- 2882510 TI - Murine Ly-6 multigene family is located on chromosome 15. AB - Murine Ly-6-encoded molecules play an important role in the antigen-independent activation of lymphocytes. We have described the cloning of a cDNA encoding the protein component of an Ly-6 molecule. Hybridization studies indicated that this cDNA identified multiple DNA fragments on Southern blots. The banding pattern exhibits a restriction fragment length polymorphism from mice bearing either the Ly-6a or the Ly-6b allele. We have employed three independent chromosomal mapping techniques, somatic cell hybrids, in situ hybridization, and strain distribution pattern analysis of the restriction fragment length polymorphism of DNA from recombinant inbred lines, to ascertain the chromosomal origins of these bands. We report that all members of the Ly-6 multigene family are tightly linked on chromosome 15 and have been regionalized by in situ hybridization analysis to band 15E on the distal portion of this chromosome. Linkage analysis has indicated that the Ly-6 genes are located within 1 map unit of Env-54 (a retroviral envelope restriction fragment length polymorphism probe), 3 map units from ins-1, (insulin-related gene), and 4 map units from the protooncogene c-sis. The possible involvement of the Ly-6 lymphocyte activation and differentiation antigen genes in chromosome 15-related lymphoid malignancies is discussed. PMID- 2882512 TI - The gene encoding the epsilon subunit of the T3/T-cell receptor complex maps to chromosome 11 in humans and to chromosome 9 in mice. AB - The T3 complex is composed of three polypeptide chains that are both structurally and functionally associated with the receptor for antigen on the surface of human T lymphocytes. In a series of experiments utilizing both somatic cell hybrids and chromosomal hybridization in situ, the genes encoding two members of the human T3 complex, T3-delta and T3-epsilon, were found to reside on the long arm of chromosome 11 in band q23. The murine T3-epsilon gene was localized to chromosome 9. The location of the T3-delta and T3-epsilon genes with respect to the Hu-ets-1 gene, which is also located in 11q23, is discussed. Recent assignments of several genes, preferentially expressed in human cells of hematopoietic and neuroectodermal origins, to band q23 of human chromosome 11 and the murine equivalents to murine chromosome 9 may define a conserved gene cluster important in cell proliferation and differentiation. PMID- 2882513 TI - Modulation of tyrosine hydroxylase gene expression in the central nervous system visualized by in situ hybridization. AB - A rat tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] cDNA probe was used for in situ hybridization studies on histological sections through the locus coeruleus, substantia nigra, and the ventral tegmental area of the rat brain. Experimental conditions were established that yielded no background and no signal when pBR322 was used as a control probe. Using the tyrosine hydroxylase probe, we ascertained the specificity of the labeling over catecholaminergic cells by denervation experiments and comparison of the hybridization pattern with that of immunoreactivity. The use of 35S-labeled probe enabled the hybridization signal to be resolved at the cellular level. A single injection of reserpine into the rat led to an increase of the intensity of the autoradiographic signal over the locus coeruleus area, confirming an RNA gel blot analysis. The potential of in situ hybridization to analyze patterns of modulation of gene activity as a result of nervous activity is discussed. PMID- 2882514 TI - The congenital goiter mutation is linked to the thyroglobulin gene in the mouse. AB - Rat thyroglobulin (TG) cDNA clones were used to identify DNA restriction fragment variants among inbred mouse strains. One of these variants was shown to be closely linked to the recessive mutation congenital goiter (cog), which had previously been mapped to mouse chromosome 15. These results indicate that the structural gene for thyroglobulin is on chromosome 15 and suggest that a mutation at the site of the TG gene is the basis of the cog defect. No differences were observed between cog/cog and +/+ DNA in Southern blots using TG cDNA probes corresponding to 88% of the coding sequences, suggesting that the cog mutation is not due to a large deletion of this portion of the gene. Neither was there any obvious qualitative or quantitative difference between mutant and normal TG mRNA as judged by blot hybridization of electrophoretically fractionated thyroid RNAs. The thyroglobulin gene locus (Tgn) was mapped near the glutamic-pyruvic transaminase isoenzyme locus Gpt-1. The Tgn locus is syntenic with the c-myc protooncogene locus (Myc) in the mouse as in the rat and man. PMID- 2882515 TI - Mapping the X-linked lymphoproliferative syndrome. AB - The X-linked lymphoproliferative syndrome is triggered by Epstein-Barr virus infection and results in fatal mononucleosis, immunodeficiency, and lymphoproliferative disorders. This study shows that the mutation responsible for X-linked lymphoproliferative syndrome is genetically linked to a restriction fragment length polymorphism detected with the DXS42 probe (from Xq24-q27). The most likely recombination frequency between the loci is 4%, and the associated logarithm of the odds is 5.26. Haplotype analysis using flanking restriction fragment length polymorphism markers indicates that the locus for X-linked lymphoproliferative syndrome is distal to probe DXS42 but proximal to probe DXS99 (from Xq26-q27). It is now possible to predict which members of a family with X linked lymphoproliferative syndrome are carrier females and to diagnose the syndrome prenatally. PMID- 2882516 TI - Specific binding of atrial natriuretic factor in brain microvessels. AB - Cerebral capillaries constitute the blood-brain barrier. Studies of specific receptors (neurotransmitters or hormones) located on this structure can be performed by means of radioligand-binding techniques on isolated brain microvessels. We examined on pure bovine cerebral microvessel preparations the binding of atrial natriuretic factor (ANF), using 125I-labeled ANF. Saturation and competition experiments demonstrated the presence of a single class of ANF binding sites with high affinity (dissociation constant, approximately 10(-10) M) and with a binding capacity of 58 fmol/mg of protein. The binding of 125I-labeled ANF to brain microvessels is specific, reversible, and time dependent, as is shown by association-dissociation experiments. The demonstration of specific ANF binding sites on brain microvessels supposes a physiological role of ANF on brain microvasculature. The coexistence of ANF and angiotensin II receptors on this cerebrovascular tissue suggests that the two circulating peptides may act as mutual antagonists in the regulation of brain microcirculation and/or blood-brain barrier function. PMID- 2882517 TI - Thy-1+ dendritic epidermal cells belong to the T-cell lineage. AB - The murine epidermis contains a population of dendritic, Thy-1+ cells (Thy-1+ DEC). Although it is now clear that these cells are of bone marrow origin, extensive morphological, histochemical, and cell-membrane marker studies have not definitively placed them in any known hematopoietic differentiation pathway. Based on the observation that Thy-1+ DEC can be propagated in vitro with Con A and interleukin 2, we have established three cell lines (Tehy 184, Tehy 245, and Yety 245) that can be continuously grown in medium with lectin-lymphokine-rich culture supernatants of rat spleen cells. With the exception of the loss of reactivity with anti-asialo-GM1 antibodies (Tehy 184 and Tehy 245) and the gain of interleukin 2 receptor expression, the cultured cell lines bear the same surface characteristics as freshly isolated Thy-1+ DEC: Thy-1+, Ly-5+, Lyt-1-, Lyt-2-, L3T4-, Ia-, sIg-. Using Southern and RNA gel blot analysis, we now demonstrate that these Thy-1+ DEC-derived cell lines exhibit various patterns of rearrangements in the gene complexes encoding the T-cell receptor (related) beta and gamma chains and contain mature and/or incomplete transcripts from the T-cell receptor alpha- and beta-chain genes, as well as transcripts from the receptor related gamma-chain genes. Tehy 184 cells, the only cells containing both mature alpha- and beta-chain transcripts, react positively with the F23.1 monoclonal antibody, which recognizes the product of a subset of T-cell receptor beta-chain variable region gene segments. This antibody precipitates a surface protein of 84 88 kDa from these cells that after reduction separates into two 40- to 44-kDa chains, characteristic of Ti alpha/beta heterodimers. These data strongly suggest that Thy-1+ DEC belong to the T-cell lineage and point to the epidermis as a site either of immature thymocyte migration or of extrathymic T-cell differentiation. PMID- 2882518 TI - The first external domain of the nonobese diabetic mouse class II I-A beta chain is unique. AB - The nonobese diabetic mouse is recognized as an important animal model for human insulin-dependent diabetes mellitus. One of the components of susceptibility to this disease has been mapped to the major histocompatibility complex. In this study, full-length cDNA clones encoding the I-A alpha and beta chains from the nonobese diabetic mouse have been isolated and sequenced. They are identical to the sequences previously determined from the H-2d haplotype except for the sequence encoding the first external domain, the leader peptide, and the 5' untranslated region of the I-A beta chain molecule. Most strikingly, there are five consecutive nucleotide substitutions which lead to two radical amino acid changes in a region that is conserved between human and mouse. We suggest that the unique structure of the first external I-A beta chain domain is a major determinant in the disease susceptibility that maps to the major histocompatibility complex of the nonobese diabetic mouse. PMID- 2882519 TI - Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency. AB - We investigated the peroxisomal beta-oxidation system in liver from a patient with clinical features similar to those in the cerebrohepatorenal (Zellweger) syndrome and with elevated levels in body fluids of very-long-chain fatty acids and intermediates in the biosynthesis of bile acids. The peroxisomal beta oxidation of fatty acids, measured as the cyanide-insensitive formation of [14C]acetyl units from [14C]palmitoyl-CoA, was very low in the patient (less than 10% of the values in control subjects). Immunoblotting experiments using antibodies to peroxisomal beta-oxidation enzymes indicated that peroxisomal 3 oxoacyl-CoA thiolase (acyl-CoA:acetyl-CoA C-acyltransferase, EC 2.3.1.16) was deficient. Addition of purified rat-liver peroxisomal 3-oxoacyl-CoA thiolase to a reaction mixture containing liver homogenate from the patient restored peroxisomal beta-oxidation. We conclude that the deficiency of peroxisomal 3 oxoacyl-CoA thiolase is responsible for the very low peroxisomal beta-oxidation activity and for the accumulation of very-long-chain fatty acids and intermediates in the biosynthesis of bile acids. Furthermore, the finding that both very-long-chain fatty acids and abnormal bile acids accumulate in this patient suggests that a single peroxisomal 3-oxoacyl-CoA thiolase is involved in the oxidative chain shortening of both very-long-chain fatty acids and the coprostanoic acids. PMID- 2882521 TI - Component deficiencies. 3. The second component. PMID- 2882522 TI - Adsorption of benzodiazepines on charcoal and its correlation with in vitro and in vivo data. PMID- 2882520 TI - Superactive octapeptide somatostatin analogs containing tryptophan at position 1. AB - We synthesized a series of octapeptide analogs of somatostatin, containing N terminal tryptophan or another amino acid followed by the hexapeptide sequences Cys-Phe-D-Trp-Lys-Thr-Cys or Cys-Tyr-D-Trp-Lys-Val-Cys and a C-terminal threoninamide or tryptophanamide. After purification by HPLC, the inhibitory activities of these analogs on the release of growth hormone (somatotropin) in rats were determined in vivo. The eight octapeptides with an N-terminal tryptophan residue were found to have a greater inhibitory effect than somatostatin. The most potent of these analogs, D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys Thr-NH2, was 94.3 times more active than somatostatin. The other analogs, in order of decreasing potency, were Ac-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2, D Trp(For)-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2, D-Trp-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr NH2, Ac-Trp(For)-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2, Ac-Trp-Cys-Tyr-D-Trp-Lys-Val Cys-Thr-NH2, D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Trp-NH2, and D-Trp-Cys-Tyr-D-Trp-Lys Val-Cys-Trp-NH2. The growth hormone inhibitory activity of these analogs was from 53.7 to 11.6 times greater than that of somatostatin. The octapeptides containing D- or L-tryptophan at the N-terminus, phenylalanine at position 3, and threonine at position 6 exhibited a greater inhibitory effect on growth hormone release than that of the analogs with tyrosine and valine at positions 3 and 6, respectively. Substitution of D-tryptophan for D-phenylalanine at the N-terminus in the octapeptide containing phenylalanine in the third, threonine in the sixth, and threoninamide in the C-terminal position also increased the growth hormone release inhibitory activity. Time-course assay showed that D-Trp-Cys-Phe-D-Trp Lys-Thr-Cys-Thr-NH2 (RC-98-I), in a dose of 1 microgram/kg of body weight, inhibited the release of growth hormone for at least 3 hr. In view of their high activity and prolonged duration of action, some of these analogs could be useful clinically. PMID- 2882523 TI - Beta-adrenergic agonists reduce spontaneous motor activity through either beta 1 or beta 2 receptors. AB - In mice, the clenbuterol-induced decrease in spontaneous motor activity was antagonized by IPS-339 (beta 2 antagonist) but not by betaxolol (beta 1 antagonist), whereas the isoproterenol-induced decrease in spontaneous motor activity was completely antagonized by betaxolol and only partially by IPS-339. It can be concluded that the clenbuterol-induced decrease in spontaneous motor activity is of the beta 2-type, whereas that induced by isoproterenol is essentially of the beta 1 type. In addition, chronic treatment with clenbuterol induced a tachyphylaxis to the effect of clenbuterol but not of isoproterenol. After chronic administration of tricyclic antidepressants (imipramine and desipramine) the number of cortical beta 1 adrenergic receptors decreased without impairing the clenbuterol-induced decrease in spontaneous motor activity. We conclude that beta 2 adrenergic receptors mediate the clenbuterol-induced decrease in spontaneous motor activity and the tachyphylaxis to this effect after chronic treatment. PMID- 2882524 TI - A new method for screening anxiolytic drugs in rats. AB - In order to evaluate the anxiolytic action of drugs, a simple experimental procedure using a corridor-type runway was designed. In this apparatus, five food pellets were set in a row on a plastic platform. Rats with one day food deprivation take a food pellet and then usually return to the start box. The time required to take 5 pellets (total time) and the number of returns were recorded. Diazepam (DZP) at 1-3.2 mg/kg and zopiclone (ZOP) at 10 mg/kg caused decreases in both parameters. These effects were blocked by the benzodiazepine receptor blocker, Ro15-1788, at 10 mg/kg. However, tracazolate failed to produce any change in both parameters. Haloperidol and imipramine prolonged the total time while reducing the number of returns. In contrast to DZP and ZOP, pentetrazol, well known to possess an anxiogenic effect, prolonged the total time. These results suggest that decreases in both the total time and the number of returns produced by DZP and ZOP may be related to their anxiolytic action which is mediated by a benzodiazepine receptor. Therefore, this procedure would be a simple and selective method for detecting benzodiazepine-type anxiolytics. PMID- 2882525 TI - Ocular pharmacokinetics of dapiprazole. AB - Dapiprazole is a drug having specific alpha 1 adrenergic blocking properties. Following topical instillation on the eye, it crosses the corneal epithelium reaching high concentrations in the ocular tissue and producing a prompt miotic and hypotensive effect. The high concentration ratio between ciliary bodies and iris versus aqueous humor suggests a peculiar affinity for these structures containing adrenoceptors of the alpha type. The very low concentrations in the plasma, as compared to those after systemic administration, and in the fellow eye indicate that the systemic absorption is negligible. PMID- 2882526 TI - Verapamil, diltiazem and nifedipine inhibit vascular responses to noradrenaline, acetylcholine and 5-hydroxytryptamine in human saphenous vein. AB - Verapamil (0.02-2 microM), diltiazem (0.22-8.14 microM) and nifedipine (0.29-8.96 microM) produced concentration-dependent relaxation of human isolated saphenous vein. Based on the EC50 values of the calcium entry blockers, verapamil (relative potency = 1) was 7 and 5 times as potent as nifedipine and diltiazem, respectively, in producing relaxation of the human saphenous vein. In addition, verapamil, diltiazem and nifedipine inhibited the vascular responses (i.e. contractions) produced by noradrenaline (0.03-36 microM), acetylcholine (0.05-55 microM) and 5-hydroxytryptamine (0.02-25 microM) and to KCl (10-100 mM). It was concluded that verapamil, diltiazem and nifedipine relaxed the human isolated saphenous vein, verapamil being more potent than diltiazem or nifedipine, and modified the vascular response to vasoconstrictor agents, e.g. noradrenaline, acetylcholine, 5-hydroxytryptamine and KCl. Thus verapamil, diltiazem and nifedipine may inhibit calcium influx through both potential and receptor operated calcium ion channels. PMID- 2882527 TI - Effect of xamoterol, a beta 1-adrenoceptor partial agonist, on myocardial pH decreased by coronary occlusion in dogs. AB - The effect of xamoterol on ischemic myocardial pH was examined in dogs. Partial occlusion of the left anterior descending coronary artery (LAD) decreased myocardial pH from 7.52-7.63 to 6.80-6.85. Xamoterol was injected intravenously 30 min after LAD occlusion that lasted for 90 min. Xamoterol (30 or 70 micrograms/kg) increased the myocardial pH that had been decreased by partial occlusion, the degree of pH increase being greater with 30 micrograms/kg than with 70 micrograms/kg, but at the dose of 200 micrograms/kg it did not increase. In the nonischemic normal heart, xamoterol (30 or 70 micrograms/kg, i.v.) had no marked effect on hemodynamic parameters, but the drug (200 micrograms/kg, i.v.) increased contractile force and heart rate with a transient decrease of myocardial pH. It is concluded that only the small dose (30 or 70 micrograms/kg) of xamoterol is effective in restoring the myocardial pH that has been decreased by partial occlusion of the LAD. PMID- 2882528 TI - Phospholipases in snake venoms and their effects on nerve and muscle. PMID- 2882529 TI - Biochemistry and physiology of brain ammonia. PMID- 2882530 TI - Effects of various soyasaponins on liver tyrosine aminotransferase activity induced by cortisone in adrenalectomized rats. PMID- 2882531 TI - Adolescents with learning problems. AB - The adolescent with learning problems presents a multifaceted diagnostic and therapeutic challenge to the primary care clinician. The adolescent failing in school often manifests secondary affective symptoms that tend to obscure underlying developmental deficits. Inadequate educational experiences, family stress, environmental deprivation, and preoccupation with nonacademic sources of gratification can further cloud the picture. Efforts at remediation must overcome the tendency of medical and school professionals, parents, and students themselves to be overly pessimistic about the long-term outcome. With the knowledge of the common causes of school failure and developmental dysfunction in this age group, the general physician can reach a reasonable diagnosis, develop a functional profile of strengths and weaknesses, and collaborate with parents, educators, and the adolescent to effect a comprehensive management plan. The physician's ongoing involvement can be a very important factor stimulating the school to continue to evaluate an individual student's needs and abilities. Parents may need assistance to recognize their child's own strengths and to help the child utilize them appropriately. If the adolescent is helped to see that he or she can make important contributions to society within the spectrum of his or her talents, then the clinician has played a crucial role in the development of a potentially happy and successful adult. PMID- 2882532 TI - [A quantitative analysis of the EEG changes during the administration of medazepam and diazepam--a comparison of the results analyzed by the wave form recognition method and the FFT method]. PMID- 2882533 TI - Seroepidemiology of adult T-cell leukemia virus infection and analysis of sero positive cases in Taiwan. AB - For a seroepidemiologic study of adult T-cell leukemia virus (ATLV) infection in Taiwan, the gelatin particle agglutination technique and the indirect immunofluorescence method were used for anti-ATLV titration. Sporadic sero positive cases were found all over the Taiwan districts except among the aborigines (0/947). Sero-positive rates ranged from 0 to 5.6% (except ATL family) and a total of 48 cases were found in 3682 Han-Chinese. Among them 9 cases were newly found in family surveys, and 39 cases were observed in random samples. As an average positive rate was 1.0%, by calculation about 80,000 sero-positive cases are supposed to be present in Taiwan. A most remarkable feature of the sero positive cases was the high rate in couples. Various patterns of sero-positive cases existed in pedigrees. Anti-ATLV positive sera of Chinese living in Taiwan and Japanese were compared by immunoprecipitation and there was no difference between them. The possible infection route from Japan to Taiwan is discussed. PMID- 2882534 TI - Suanzaorentang, and anxiolytic Chinese medicine, affects the central adrenergic and serotonergic systems in rats. AB - Previously, we found that the ancient Chinese remedy of Suanzaorentang was a promising anxiolytic drug (Chen and Hsieh, 1985; Chen and Hsieh, 1985a). We also found that Suanzaorentang decreased the turnover rate of central monoamines and central catecholaminergic activity (Hsieh, et al., 1986). In this study, we found that 5-hydroxytryptophan (5-HTP) induced decrease in locomotor activity was significantly antagonized by Suanzaorentang, p-chlorophenylalanine (p-CPA) induced increase in locomotor activity was significantly inhibited by Suanzaorentang, Suanzaorentang had no significant effects on baclofen, muscimol, aminooxyacetic acid (AOAA) and thiosemicarbazide induced changes in locomotor activity, Suanzaorentang significantly decreased vanillylmandelic acid (VMA) in striatum and hippocampus, homovanillic acid (HVA) in hippocampus and 5 hydroxyindol acetic acid (5-HIAA) in striatum and hypothalamus, Suanzaorentang significantly reversed the alpha-methyltyrosine (alpha-MT) produced decrease in DA concentrations in striatum and hippocampus, and (6) Suanzaorentang significantly reversed the p-CPA produced decrease in 5-HT concentrations on amygdala. These facts implied that Suanzaorentang might decrease the serotonergic activity but have no significant effect on GABAergic activity. The main locus of action might be in the limbic system. PMID- 2882535 TI - Lithium distribution in mania: plasma and red blood cell lithium, clinical state, and monoamine metabolites during lithium treatment. AB - We examined red blood cell (RBC) and plasma lithium concentrations and RBC/plasma lithium ratios in 14 manic patients during lithium treatment as part of the National Institute of Mental Health's Collaborative Program on the Psychobiology of Depression, Biological Studies. All of the lithium measures increased during treatment, especially RBC lithium. There were positive correlations between the RBC lithium concentration and the RBC/plasma lithium ratio and their maximal values in a single-dose pharmacokinetic experiment before treatment. After 5 and 16 days of treatment, patients with good subsequent outcome had higher RBC/plasma lithium ratios than did patients with poor outcome. Early in treatment, there was a negative correlation between lithium concentrations and severity of mania. During treatment, there was a negative correlation between RBC lithium and urinary MHPG excretion. There was a positive correlation between RBC or plasma lithium during the first few days of treatment and subsequent reduction in norepinephrine excretion during treatment. At 3 weeks, there were negative correlations between reductions in catecholamine measures and lithium concentrations. These data suggest that there are changes in the sensitivity of behavior and catecholamine function to lithium during treatment. RBC concentrations of lithium appear to be a potentially useful indicator of its behavioral and neurochemical effects. PMID- 2882536 TI - Neurohormonal functioning and sexual orientation: a theory of homosexuality heterosexuality. PMID- 2882537 TI - Self-injection of d,1-3,4-methylenedioxymethamphetamine (MDMA) in the baboon. AB - MDMA (d,1-3,4-Methylenedioxymethamphetamine HCl; "ecstasy") self-injection (0.1 3.2 mg/kg/injection) was examined in baboons under conditions in which baseline responding was maintained by intravenous injections of cocaine HCl (0.32 mg/kg/injection). Drug was available under a FR 160-response schedule of intravenous injection. Each drug injection was followed by a 3-h time out allowing a maximum of eight injections per day. MDMA or MDMA vehicle (saline) was substituted for cocaine for a period of 14 or more days followed by a return to the cocaine baseline. MDMA (0.32-3.2 mg/kg/inj) maintained more injections and higher responses rates than were maintained by saline. The maximal number of injections maintained by MDMA and the maximal response rate maintained by MDMA were less than those maintained under baseline conditions with cocaine. The highest dose of MDMA tested maintained a cyclic pattern of self-injection, i.e., days of high numbers of injections intermixed with days of low numbers of injections. At the highest dose of MDMA tested, concurrent food maintained behavior was suppressed to an extent that food intake was also decreased. PMID- 2882539 TI - A simple and rapid method for assessing similarities among directly observable behavioral effects of drugs: PCP-like effects of 2-amino-5-phosphonovalerate in rats. AB - Directly observable behavioral effects of the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (AP5) (10-1,000 mg/kg IP, 0.18 5.6 mumol/rat ICV) and of phencyclidine (PCP) (3.2-56 mg/kg IP, 0.032-3.2 mg/rat ICV), ketamine (10-100 mg/kg), amphetamine (1-18 mg/kg), apomorphine (0.1-5.6 mg/kg), chlordiazepoxide (1-100 mg/kg), and pentobarbital (3.2-56 mg/kg) were studied in rats. Pharmacologically specific results were obtained rapidly and reliably, using a cumulative dosing procedure. Cluster analysis grouped the drug treatments, on the basis of their similarities in producing different behavioral activities, into three main clusters; characteristically, stimulant drugs (amphetamine, apomorphine) produced sniffing and gnawing; PCP-like drugs (PCP, ketamine) produced locomotion, sniffing, swaying and falling; sedative drugs (pentobarbital, chlordiazepoxide) produced loss of righting. The behavioral effects of ICV administration of AP5 were more similar to the effects of PCP-like drugs than to the effects of either stimulant or sedative drugs, thus supporting the hypothesis that the behavioral effects of PCP-like drugs may result from reduced neurotransmission at excitatory synapses utilizing NMDA preferring receptors. The present procedure is simple, rapid and may provide a useful approach in the classification of behaviorally active drugs. PMID- 2882538 TI - Possible neuronal mechanisms involved in neurotensin-induced catalepsy in mice. AB - The neuronal mechanisms of neurotensin (NT)-induced catalepsy were investigated in mice. NT administered intracerebroventricularly (ICV 0.5, 1.0 and 2.0 micrograms) produced catalepsy in a dose-dependent fashion. A significant effect was observed at 2.0 micrograms and a maximal effect 2-3 h after injection. The NT induced catalepsy was inhibited by pretreatment with atropine, trihexyphenidyl or biperiden (each drug, 0.8-5.0 mg/kg, IP), anticholinergic drugs, and L-DOPA (100, 200 mg/kg, IP). However, the catalepsy was not significantly antagonized by p chlorphenylalanine (300 mg/kg X 3 days, IP) or methysergide (5, 10 mg/kg, IP), antiserotonergic drugs, and was not potentiated by the GABAergic drugs, aminooxyacetic acid (25 mg/kg, IP) or muscimol (1 mg/kg, IP). In addition, the NT induced catalepsy was dose-dependently reduced by antihistamines, such as diphenhydramine (0.8-10 mg/kg, IP) and tripelennamine (0.4-5.0 mg/kg, IP) and was potentiated after treatment with histidine (250, 500 mg/kg, IP), a precursor of brain histamine. NT-induced catalepsy was also reduced by ICV pretreatment with diphenhydramine (1-5 micrograms/rat), a H1 antagonist, but not by cimetidine (5, 20 micrograms/rat), a H2 antagonist. These findings suggest that the catalepsy induced by NT may involve not only central cholinergic and dopaminergic mechanisms but also a histaminergic mechanism mediated via H1-histamine receptors, and seems to differ from the catalepsy induced by neuroleptics. PMID- 2882541 TI - Enhanced stereotyped response to apomorphine after chronic D-1 blockade with SCH 23390. AB - Rats were treated for 21 days with the selective D-1 blocker SCH 23390 (0.1 mg/kg SC). Threshold doses of apomorphine for hypermotility (0.15 mg/kg SC) and for stereotyped response (0.25 mg/kg SC) were given 7, 21, 35, and 77 days after discontinuation of the chronic treatment. The rats always showed enhanced stereotyped response to the higher dose of apomorphine but never any change in their motility response to the lower dose of dopamine agonist. This finding may represent a behavioral correlate of the reported supersensitivity of D-1 receptors induced by SCH 23390. PMID- 2882542 TI - Delusional depression: phenomenology and response to treatment. AB - In this retrospective study demographic and clinical characteristics, personality traits, family psychiatric history and response to treatment were compared in 55 delusional and 40 nondelusional hospitalized patients who met DSM-III criteria for major depression. Male delusional depressives had a greater frequency of delusional ideas at the index episode than female delusionals. Delusional depressives had a greater frequency of family history for alcoholism, a smaller frequency of previous depressive episodes and tended to respond more favorably to treatment with electroconvulsive therapy or tricyclic antidepressants combined with neuroleptics than to antidepressants alone. The findings and the implications arising from them are discussed. PMID- 2882540 TI - Yawning is elicited by D2 dopamine agonists but is blocked by the D1 antagonist, SCH 23390. AB - The subtype of dopamine (DA) receptors mediating the yawning response to DA agonists was determined in rats. Yawning was elicited both by the mixed D1-D2 agonist apomorphine and by the specific D2 agonist LY 171555, but not by the selective D1 agonist SKF 38393. Both apomorphine- and LY 171555-induced yawning were antagonized not only by the selective D2 antagonist sulpiride but, unexpectedly, also by the selective D1 antagonist SCH 23390. The results suggest that DA receptors mediating the yawning response are of the D2 type, and that these receptors are connected with D1 receptors in such a way that the blockade of the latter results in the functional inactivation of the former. PMID- 2882543 TI - Cognitive disturbances in chronic schizophrenia: formal thought disorder and basic symptoms. AB - We investigated 37 chronic schizophrenic patients with two objective rating scales (AMDP and Brief Psychiatric Rating Scale; BPRS) and compared the questioned symptoms with the Frankfurter Beschwerde Fragebogen (FBF), a questionnaire for subjective complaints which are close to the uncharacteristic 'basic' symptoms of schizophrenic patients. It was pointed out that the questions in the FBF relate mainly to uncharacteristic symptoms like disturbances of perception, concentration, attention, perceiving, and memory. These subjective symptoms of the FBF show a few correlations with the AMDP/BPRS rating. The total score of the FBF gave no further information about social functioning of patients with cognitive disturbances. PMID- 2882544 TI - Use of benzodiazepines in a coronary care unit. PMID- 2882545 TI - Esmolol: a novel ultra-short acting beta-adrenoreceptor blocking agent. PMID- 2882546 TI - Coexistence of neuronal messengers: a new principle in chemical transmission. Proceedings of the Marcus Wallenberg Symposium. Stockholm, 26-28 June, 1985. PMID- 2882547 TI - Transmitter status in cultured sympathetic principal neurons: plasticity, graded expression and diversity. PMID- 2882548 TI - Impulse activity differentially regulates co-localized transmitters by altering messenger RNA levels. PMID- 2882549 TI - Coexistence during ontogeny and transplantation. PMID- 2882550 TI - Chemical signalling in the nervous system. PMID- 2882551 TI - Multiple chemical messengers in hypothalamic magnocellular neurons. PMID- 2882552 TI - Purines and cotransmitters in adrenergic and cholinergic neurones. PMID- 2882553 TI - Chemical coding of enteric neurons. PMID- 2882554 TI - Multiple co-existence of peptides and classical transmitters in peripheral autonomic and sensory neurons--functional and pharmacological implications. PMID- 2882555 TI - The diffuse neuroendocrine system: peptides, amines, placodes and the APUD theory. PMID- 2882556 TI - On the possible roles of noradrenaline, adenosine 5'-triphosphate and neuropeptide Y as sympathetic cotransmitters in the mouse vas deferens. PMID- 2882557 TI - Chemical transmission and Dale's principle. PMID- 2882558 TI - Functional consequences of coexistence of classical and peptide neurotransmitters. PMID- 2882559 TI - Coexistence of neuronal messengers--an overview. PMID- 2882560 TI - Coexistence of neuronal messengers and molecular selection. PMID- 2882561 TI - Convergence of small molecule and peptide transmitters on a common molecule cascade. PMID- 2882562 TI - Application of monoclonal antibodies and dietary antioxidant-based animal models to define human exposure to aflatoxin B1. PMID- 2882563 TI - A somatostatin receptor negatively coupled to adenylate cyclase in the human gastric cell line HGT-1. AB - Somatostatin receptors are demonstrated in the human derived gastric cell line HGT-1. Using 125I-Tyr11-somatostatin as ligand, two classes of sites were characterized with apparent dissociation constants KD1 = 0.9 X 10(-10) M and KD2 = 4 X 10(-9) M and maximum binding capacities of N1 = 20 and N2 = 556 fmol per mg protein, respectively. These values are close to those previously reported in freshly isolated parietal cells (Reyl, F., Silve, C. and Lewin, M.J.M., Somatostatin receptors on isolated gastric cells. In S. Bonfils et al. (Eds.), Hormone Receptors in Digestion and Nutrition, Elsevier/North-Holland, Amsterdam, 1979, pp. 391-400). Somatostatin binding to the high affinity sites was partially inhibited by the non-hydrolysable guanyl nucleotide analog Gpp(NH)p and by pretreating the cells with islet activating protein (IAP). Furthermore, IAP counteracted the inhibitory effect of somatostatin on histamine stimulation of adenylate cyclase. These findings are interpreted in terms of somatostatin interaction with the 41,000 Da adenylate cyclase GTP-dependent inhibitory subunit, Ni. PMID- 2882564 TI - The influence of mammalian and teleost somatostatins on the secretion of growth hormone from goldfish (Carassius auratus L.) pituitary fragments in vitro. AB - The effect of various vertebrate somatostatins (SRIF) on basal growth hormone (GH) secretion from goldfish pituitary fragments was studied using an in vitro perifusion system. SRIF-14 caused a rapid and dose-dependent decrease in the rate of GH release from goldfish pituitary fragments. The half-maximal effective dose (ED50) of SRIF-14 was calculated as 1.3 nM following exposure to two minute pulses of increasing concentrations of SRIF-14, whereas the ED50 of SRIF-14 calculated after continuous exposure to sequentially increasing doses of SRIF-14 was 65 nM. This difference suggests that the pituitary fragments were less responsive to SRIF-14 in the latter experiment, possibly as a result of previous exposure to SRIF-14. SRIF-28 was found to be equipotent with SRIF-14 in decreasing basal GH secretion from the goldfish pituitary. In contrast, catfish SRIF-22, a uniquely teleost SRIF isolated from catfish pancreatic islets, did not alter GH secretion. These results provide further support for the hypothesis that SRIF-14 or a very similar molecule functions as a GH release-inhibiting factor in teleosts, indicating that this action of SRIF-14 has been fully conserved throughout vertebrate evolution. PMID- 2882565 TI - Glucagon, glicentin, proglucagon, PYY, PP and proPP-icosapeptide immunoreactivities of rectal carcinoid tumors and related non-tumor cells. AB - Glucagon/PP-related peptides were detected immunohistochemically in 18 out of 22 cases of rectal tumors investigated. The reactive tumors showed prevalence of trabecular or mixed trabecular-acinar structure and moderate staining with Grimelius' silver and lead-hematoxylin. Three of the remaining 4 cases were characterized by reactivity for 5-hydroxytryptamine only, prevalence of a solid nest structural component and intense staining with Grimelius' silver technique and lead-hematoxylin. Fifteen of the 18 glucagon/PP-reactive cases were investigated immunohistochemically with a series of 6 sera directed against different sequences of glucagon, glicentin and proglucagon, and of 7 sera directed against PP, PYY and proPP-icosapeptide. A large spectrum of glucagon related immunoreactivities, including C-terminus and mid-portion glucagon immunoreactivity, N- and C-terminus glicentin-immunoreactivity, GLP1- and GLP2 immunoreactivity, were detected in human rectal L cells and most rectal carcinoids. With the exception of a few scattered cells in the rectal mucosa and in 3 tumors, C-terminus glucagon-immunoreactivity was obtained only after trypsin or subtilisin treatment of tissue sections. Both PYY and PP/proPP-like peptide(s) were detected in rectal L cells and carcinoids, with prevalence of PYY in normal cells and PP/proPP-like peptides in tumor cells. It is concluded that the same or closely related hormone/prohormone sequences are synthesized and stored in rectal endocrine cells and carcinoid tumors although differences of quantitative expression, post-translational cleavage or reactivity to antibodies may occur. The usefulness of protease treatments of tissue sections to unmask immunoreactivities of uncleaved propeptides or fixative-denatured peptides is outlined. PMID- 2882566 TI - Methods of intervention to modify drinking patterns in heavy drinkers. AB - More than 30,000 individuals have been investigated in the continuous screening and intervention study in Malmo. Large subsamples of individuals with different levels of serum gamma-glutamyltransferase (GGT) have been characterized and followed up; GGT has proved to be a useful and simple tool in identifying and treating heavy drinkers and monitoring their outcome. In the intervention study, counseling and repeated feedback of GGT results in a group of middle-aged heavy drinkers led to a significant reduction in sick absence, hospitalization, and mortality compared with those in a control group over a period of 6 to 8 years. At follow-up, about 15% of middle-aged men in the general population had serious alcohol problems. Assessment and treatment of heavy drinkers within general medicine would provide a very considerable impact on the total problem of alcohol related disease. PMID- 2882567 TI - Perspectives in the treatment of reversible airway obstruction. AB - The pharmacological therapy of asthmatic syndromes is based essentially on the programmed use of disodium cromoglycate, beta-2-stimulants, antimuscarinics, theophyllines and corticosteroids. However, the continual progress being made in pathogenesis and pharmacology suggests, to an ever-increasing extent, the application of new therapeutic approaches for these diseases, some of which are fairly interesting from a speculative point of view although they are as yet of limited practical value. Calcium antagonists and alpha-blockers have a mild anti reactive effect but this is not sufficiently potent to justify use of these products in the treatment of asthma unless there are also cardiovascular disorders for which these drugs are particularly indicated. Despite the initial promising prospects, all attempts to obtain PGE analogues of therapeutic value as antiasthmatics have proved fruitless. Research into orally active chromone derivatives has proved equally unproductive. On the other hand, certain new inhalatory chromones are decidedly more promising. Specific antagonization of mediators (histamine, prostaglandin, leukotrienes) did not produce the effect hoped for in asthma, but this was foreseeable insofar as the major pathogenic mediators are too vast in number (and no doubt there are still many more to be discovered) to allow one to conceive it possible to achieve a satisfactory therapeutic effect by merely blocking some of them. Inflammation of the bronchial wall is currently considered to be one of the basic pathogenic factors provoking the recurrence of asthma: this is proved indirectly by the potent antiasthmatic effect of corticosteroids which are the most effective anti-inflammatory agents. As regards nonsteroidal anti-inflammatory drugs (NSAID), however, matters are more complicated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882568 TI - Comments on acute studies. AB - Sixteen papers which have examined the effects of Duovent (a combination of fenoterol 200 micrograms and ipratropium bromide 80 micrograms) in the treatment and prevention of bronchospasm by acute studies are reviewed. The studies suggest that the use of a combination of anticholinergic and beta 2-adrenergic drugs is justified, because the dominant mechanism in bronchospasm is the effect of acetylcholine on muscarinic receptors and because ipratropium bromide increases the action of fenoterol, so as to obtain prolonged bronchospasmolytic and antibronchoconstrictive effects with halved doses of beta 2-agonist. PMID- 2882569 TI - Reversible airway obstruction: neurohumoral mechanisms and treatment. Lecture on asthma: clinical overview. AB - Asthma is an airway obstruction which is reversible, either spontaneously or in response to treatment. Repeated peak expiratory flow rate (PEFR) measurements, up to six times daily, allows this characteristic reversibility to be recognised, to guide diagnosis and therapy. Chronic asthmatics may eventually become relatively irreversible, and then appear similar to chronic bronchitics - unless an adequate history is taken. The commonest world-wide allergen is the fecal pellet of the house mite. Modern therapy of asthma starts with inhaled beta 2 agonists, but difficulty in using metered dose inhalers is helped by the 'spacer', or reservoirs (e.g. 'Nebuhaler'). Interaction between slow-release oral theophyllines and beta 2 agonists by inhalation maximises bronchodilatation but minimises tremor. High-dose ipratropium inhalation, as isotonic wet nebulisation with a beta 2 agonist, is useful in acute severe asthma. High doses of inhaled topical steroid are valuable in the difficult asthmatic, but pituitary adrenal suppression occurs if dosage exceeds 1,500 micrograms/day. Cromoglycate and a beta 2 agonist by inhalation can prevent exercise-induced asthma. Long-term oral steroids (never over 10 mg/day) are only used if inhaled therapy (+/- oral slow release theophyllines) fails. Acute severe asthma needs parenteral steroid, parenteral beta 2 agonist, high-dose beta 2 agonist by inhalation, oxygen and hospital admission. Ventilation is increased in the acute severe asthmatic with hypoxia and low PCO2. In 90 asthmatic deaths surveyed in Britain, half had failed to realise the severity. PMID- 2882570 TI - Reversible airway obstruction: neurohumoral mechanisms and treatment. Lecture on nocturnal asthma. AB - Nocturnal wheeze has been known for at least 300 years, but only recently widely recognised. Wakening between 3 and 4 a.m. with wheeze may be associated with a 'morning dip' in peak expiratory flow rate (PEFR), worse in REM sleep, and with a circadian rhythm. Earlier suggestions that plasma histamine rose with nocturnal bronchoconstriction cannot be confirmed, but circulating adrenaline may be reduced in asthmatics at night. Hypoxia at night is common in asthmatics, associated with hypoventilation in REM sleep. Increasing frequency of nocturnal wheeze may herald acute severe asthma. Beta 2 agonists inhaled on retiral do not last to prevent the 'morning dip' in PEFR, but slow-release theophyllines can prevent this, and also relieve symptoms. However, sleep is still disturbed (by EEG criteria), as is nocturnal hypoxaemia. Nocturnal wheeze and/or 'morning dip' in PEFR occur in both atopic and non-atopic asthmatics, and the mechanism of nocturnal wheeze remains to be determined. Recognition of this common symptom remains a major indication for oral slow-release theophyllines. PMID- 2882571 TI - Antiasthmatic drugs--opening remarks. PMID- 2882572 TI - Beta-adrenergic bronchodilators. AB - Long-acting beta 2-selective agonists have become a major form of therapy of reversible airway obstruction. Modern agents are effective by all routes of administration and can both eliminate bronchospasm as well as prevent its occurrence. Many drugs such as albuterol, terbutaline and fenoterol have similar pharmacologic profiles, and there is frequently little to choose between them. The majority of the available data indicate that aerosol therapy produces as much bronchodilation as the oral and parenteral routes with much fewer side effects. PMID- 2882573 TI - Interaction with histamine H1-receptors and bronchospasmolytic effects of urapidil. AB - The antihypertensive drug, urapidil, competitively antagonized the histamine induced contractions in guinea pig isolated tracheal and ileal preparations. Its affinity to histamine H1-receptors was 3-fold higher than that of histamine but 10- and 30-fold weaker than that of diphenhydramine and indoramin, respectively. Urapidil did not inhibit contractions induced by muscarinic agonists in both organs. Investigations in spontaneously breathing guinea pigs showed a greater efficacy of urapidil than that of diphenhydramine in protecting the animals against histamine-induced bronchospasms, whereas acetylcholine-induced spasms were only moderately inhibited. Theophylline, at a 100-fold higher dosage than urapidil, protected the animals against both histamine and acetylcholine challenges. This experimentally observed effect of urapidil supports clinical trials in hypertensive patients suffering also from obstructive lung disease and/or allergic illness. PMID- 2882575 TI - The Baltimore Conference.(Tenth International Conference on Sarcoidosis). PMID- 2882574 TI - Update on immunology of sarcoidosis. Report from the Baltimore Conference. PMID- 2882576 TI - Pathology review--10th International Conference Baltimore 1984. PMID- 2882577 TI - Epidemiology of sarcoidosis: a report of the papers and posters presented at the tenth International Conference on Sarcoidosis, Baltimore, USA 1984. PMID- 2882578 TI - [Use of calcium antagonists in the treatment of cardiac arrhythmias]. PMID- 2882579 TI - [Clinical study of the correlation of arterial hypertension, ischemic cardiopathy and cardiac insufficiency in a group of 4,239 patients]. PMID- 2882581 TI - [Computerized isotopic angiography and echocardiography in the differential diagnosis between congestive cardiomyopathy and coronary disease]. PMID- 2882580 TI - [Prognostic significance of ST segment depression on the precordial lead in acute inferior myocardial infarction]. PMID- 2882582 TI - [Value of metoprolol in increasing the tolerance of patients with ischemic heart disease to exertion]. PMID- 2882583 TI - [Preventive treatment of unstable angina with aspirin (preliminary note)]. PMID- 2882585 TI - [A case of Fabry's disease]. PMID- 2882584 TI - [Immune reactions during treatment with propranolol]. PMID- 2882586 TI - [Microalbuminuria in incipient diabetic nephropathy]. PMID- 2882587 TI - [Minimal proteinuria in diabetes mellitus]. PMID- 2882588 TI - [Platelet function and blood coagulation in chronic renal insufficiency]. PMID- 2882589 TI - [Current status and outlook of biological therapies in mental diseases]. PMID- 2882590 TI - [The use of psychotropic drugs in elderly patients]. PMID- 2882591 TI - [Subdural empyema: a severe complication. Apropos of 4 cases]. PMID- 2882592 TI - Localization of glutamate in trigeminothalamic projection neurons: a combined retrograde transport-immunohistochemical study. AB - Trigeminothalamic projection neurons are important components of the pathways for conscious perception of pain, temperature, and tactile sensation from the orofacial region. The neurotransmitters utilized by trigeminal neurons projecting to the thalamus are unknown. By use of a monoclonal antibody specific for fixative-modified glutamate and a polyclonal antiserum against glutaminase, we recently identified neurons in the trigeminal sensory complex that contain glutamate-like immunoreactivity (Glu-LI) and glutaminase-like immunoreactivity. In the present study, we utilized combined retrograde transport immunohistochemical techniques to localize putative glutamatergic trigeminothalamic neurons. Following injection of the retrograde tracer, wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP), into the ventroposterior medial thalamus (VPM), the number of neuronal profiles that were double-labeled with WGA:HRP and Glu-LI was greatest in principal sensory nucleus (Pr5), followed by subnuclei interpolaris (Sp5I) and caudalis (Sp5C). The average percentages of projection neurons double-labeled with Glu-LI were approximately 60-70% in Pr5 and Sp5I and 40% in Sp5C. The majority of double-labeled profiles in Sp5C were located in the magnocellular layer, as opposed to the marginal and substantia gelatinosa layers. A large injection site that spread into the intralaminar thalamic nuclei and nucleus submedius--areas implicated in the processing of nociceptive information--resulted in an increase in the ratio of single-labeled to double-labeled projection profiles in Sp5C. These results suggest that glutamate may be the neurotransmitter for a majority of trigeminothalamic projection neurons located in Sp5I and Pr5. However, on the basis of anatomical association, glutamate does not appear to be the major transmitter for neurons in Sp5C that forward nociceptive information to the thalamus. PMID- 2882593 TI - [Intraluminal arterioplasty as therapy for severe renovascular arterial hypertension due to Takayasu arteritis: report of a case]. PMID- 2882594 TI - [Polyarteritis nodosa cutanea]. PMID- 2882595 TI - [Emboli of cholesterol crystals simulating panarteritis nodosa with joint signs]. PMID- 2882596 TI - [Sports and maxillofacial injuries: etiological and clinical aspects apropos of 46 cases. Preventive measures]. AB - Maxillofacial injuries due to sporting activities represent approximately 10% of all cases of injury admitted to the University Hospital Center, Lyon, France, and more than half of these occur in football or rugby players. The causes of these accidents (blows against another player, the ground, the field equipment or the game accessories) are discussed. Lesions are generally simple in young, fit adults and results of surgical treatment satisfactory, apart from the rare cases of facial disruption. Preventive measures include examination for aptitude for sporting activities, adequate referring of games and the wearing of helmets, masks and inter-maxillary protective bars. PMID- 2882597 TI - The immediate effect of human renal transplantation on basal and meal-stimulated levels of gastrointestinal hormones. AB - Elevated serum levels of gastrin, pancreatic polypeptide, and glucagon were found in 10 uraemic patients, whereas gastric inhibitory polypeptide and somatostatin levels were normal. After renal transplantation there was a significant reduction in serum gastrin (median, 5 pmol/l; p = 0.05, n = 9), pancreatic polypeptide (145 pmol/l; p less than 0.01, n = 9), GIP (9.5 pmol/l; p = 0.02, n = 7), and glucagon (92 pg/l; p less than 0.02, n = 9), whereas no alteration was seen in the somatostatin level. Meal stimulation produced consistent increases in serum levels of all hormones, and the response appeared to be unchanged after renal transplantation. PMID- 2882598 TI - Circulating tachykinins (substance P, neurokinin A, neuropeptide K) and the carcinoid flush. AB - Antisera of defined regional specificity have been used to measure the concentration of substance P-like immunoreactivity (SP-LI) and neurokinin A-like immunoreactivity (NKA-LI) during a meal-induced flush in 10 patients with metastatic carcinoid tumours. Although all patients flushed, NKA-LI levels in five patients and SP-LI in six patients were not elevated relative to healthy subjects (NKA-LI, less than 3 pg/ml; SP-LI, less than 10 pg/ml) both in the fasted state and after food. In the patients with elevated basal plasma tachykinin levels, increases in NKA-LI and SP-LI after food were erratic and did not correspond to a defined digestive phase or the occurrence of the flush. Chromatographic analysis of plasma demonstrated the presence of neuropeptide K and neurokinin A, and the detection of COOH-terminal fragments of substance P is consistent with the higher levels of circulating SP-LI measured with a COOH terminally directed antiserum compared with an NH2-terminally directed antiserum. Subcutaneous injection of the somatostatin analogue SMS 201-995 (50 micrograms) alleviated symptoms of flush in two of three patients but only partially suppressed NKA-LI and SP-LI concentrations. It is concluded that circulating tachykinins cannot be solely responsible for the meal-induced carcinoid flush. PMID- 2882599 TI - [Therapeutic strategy in arterial hypertension]. AB - Diuretics and beta-blocking agents have been used for several years as first-step drugs in the treatment of hypertension. There is now growing evidence that calcium channel blockers and angiotensin converting enzyme inhibitors can also be administered as first-line antihypertensive agents. These agents offer attractive features from the hemodynamic and metabolic viewpoint and with regard to side effects. Diuretics, beta-blocking agents, calcium channel blockers and angiotensin converting enzyme inhibitors, administered either alone or in combination, normalize blood pressure in almost all hypertensive patients. PMID- 2882600 TI - Beta blockers and lipoproteins: a review of current knowledge. PMID- 2882601 TI - Polyarteritis presenting with thrombocytosis and central retinal vein thrombosis. AB - We report a case of polyarteritis in a 54 year old woman who presented with marked thrombocytosis and acute blindness in one eye secondary to central retinal vein thrombosis. She also developed bilateral pulmonary infiltrates and renal failure. The diagnosis was confirmed by histological changes in the renal biopsy. Treatment with immunosuppressives, plasma exchange and antiplatelet drugs led to rapid clinical improvement and recovery of renal function and prevented further thromboembolic episodes. Plasma exchange and antiplatelet drugs should be considered in polyarteritis group of systemic vasculitis especially in the presence of thromboembolic complications or thrombocytosis. PMID- 2882602 TI - Developmental control gene sequenced. PMID- 2882603 TI - Sevenless, a cell-specific homeotic gene of Drosophila, encodes a putative transmembrane receptor with a tyrosine kinase domain. AB - The determination of cell fates during the assembly of the ommatidia in the compound eye of Drosophila appears to be controlled by cell-cell interactions. In this process, the sevenless gene is essential for the development of a single type of photoreceptor cell. In the absence of proper sevenless function the cells that would normally become the R7 photoreceptors instead become nonneuronal cells. Previous morphological and genetic analysis has indicated that the product of the sevenless gene is involved in reading or interpreting the positional information that specifies this particular developmental pathway. The sevenless gene has now been isolated and characterized. The data indicate that sevenless encodes a transmembrane protein with a tyrosine kinase domain. This structural similarity between sevenless and certain hormone receptors suggests that similar mechanisms are involved in developmental decisions based on cell-cell interaction and physiological or developmental changes induced by diffusible factors. PMID- 2882604 TI - Neurogenetic adaptive mechanisms in alcoholism. AB - Clinical, genetic, and neuropsychopharmacological studies of developmental factors in alcoholism are providing a better understanding of the neurobiological bases of personality and learning. Studies of the adopted-away children of alcoholics show that the predisposition to initiate alcohol-seeking behavior is genetically different from susceptibility to loss of control after drinking begins. Alcohol-seeking behavior is a special case of exploratory appetitive behavior and involves different neurogenetic processes than do susceptibility to behavioral tolerance and dependence on the antianxiety or sedative effects of alcohol. Three dimensions of personality have been described that may reflect individual differences in brain systems modulating the activation, maintenance, and inhibition of behavioral responses to the effects of alcohol and other environmental stimuli. These personality traits distinguish alcoholics with different patterns of behavioral, neurophysiological, and neuropharmacological responses to alcohol. PMID- 2882605 TI - Arachidonic acid metabolites and perinatal cerebral hemodynamics. PMID- 2882606 TI - [Puerperal psychosis: the case of Mrs. R]. PMID- 2882607 TI - Pain relief after arthroscopy: naproxen sodium compared to propoxyphene napsylate with acetaminophen. AB - We compared naproxen sodium (550 mg) and propoxyphene napsylate with acetaminophen (PN/A, 100 mg with 650 mg) for pain relief after arthroscopy or arthroscopic meniscectomy. Fifty-two patients entered this multicenter, double blind, randomized, parallel trial. In each drug group, pain intensity values dropped consistently throughout this six-hour study from mean baseline levels of approximately 55 on a scale of 0 to 100. Pain intensity values were lower at each hour in the naproxen sodium than in the PN/A group and significantly lower at hour 1 (P = .008). Pain intensity differences (PID, reflecting change from baseline) mirrored this trend: greater mean PIDs were seen in the naproxen sodium group at each hour, and this difference between drug groups was statistically significant at hour 1 (P = .017). One patient in the naproxen sodium group and seven patients using PN/A took a second dose within the six hours. Patients in each drug group reported five complaints. PMID- 2882608 TI - Takayasu's arteritis diagnosed in a patient with long-standing arthralgias and arthritis. AB - A 50-year-old woman had seronegative polyarthritis for three years, followed by vascular obstruction with classic Takayasu's arteritis. She responded symptomatically to high-dose steroid therapy and remains in long-term remission (joints and vasculature) after taper of medication. Literature review documents this relationship of arthritis to vasculitis in this and other types of vascular inflammation. PMID- 2882610 TI - [Therapeutic use of gastrointestinal hormones]. PMID- 2882609 TI - The importance of communication with the foci of infection in the transmission of filariasis in Indonesia. AB - Studies on the occurrence of early symptoms of filariasis have been conducted in two transmigration Units in the valley of the Wae Apu river, Buru island, Maluku Province, Indonesia. In both Units, higher disease rates were found in areas, where there was a closer contact with positive natives, higher density of the vector mosquito, and higher infective rates in the mosquitoes. PMID- 2882611 TI - Takayasu's arteritis. PMID- 2882612 TI - Takayasu's arteritis. Report of an unusual case. AB - The progression from the early pre-pulseless to the pulseless state in an unusual case of Takayasu's arteritis is presented. Several uncommon associated features are also described. The importance of the findings is briefly discussed. PMID- 2882613 TI - Advances in the diagnosis and treatment of medullary thyroid carcinoma. AB - Medullary thyroid carcinoma accounts for 5 to 10 per cent of all thyroid malignancies and may occur in a familial or a sporadic pattern. This article reviews the authors' experience with 200 patients with medullary thyroid carcinoma and outlines the recent advances made in our understanding of the biochemical properties of these cancer cells and the relationship of different tumor markers to prognosis. PMID- 2882615 TI - [Research from Buskerud: uncertainty in the care of HIV-positive patients]. PMID- 2882614 TI - Zollinger-Ellison syndrome (gastrinoma). Current diagnosis and treatment. AB - Zollinger-Ellison syndrome is being detected at an earlier stage through liberal use of serum gastrin testing and application of secretin provocative tests if needed. The peptic ulcer disease of patients with Zollinger-Ellison syndrome can usually be controlled by large doses of one of the new potent gastric acid inhibitors. A battery of preoperative localizing tests can then be applied to guide exploratory laparotomy in non-MEN I patients. The tumor should be resected if possible, and continued low gastrin levels after operation provide evidence of a complete resection. It is reasonable to perform a parietal cell vagotomy at celiotomy because it will facilitate control of acid secretion if tumor resection is not successful. The only need for total gastrectomy is in a few patients whose acid secretion cannot be controlled with H2 receptor antagonists or who cannot comply with medical therapy. When no tumor is found at celiotomy, the prognosis for long-term tumor-free survival is excellent. Unfortunately, if unresectable hepatic metastases are present at operation, the patient is likely to die from metastatic tumor. PMID- 2882616 TI - [Regulation of the IgE antibody response]. PMID- 2882617 TI - [The treatment of children with Gilles de la Tourette's syndrome]. AB - Tourette syndrome is a neuropsychiatric disorder of motor and vocal tics, with associated symptoms of obsessive-compulsive behaviors and attention deficit disorder with hyperactivity. Genetic factors seem to play a major role, but the precise mode of inheritance is still not known. Intervention includes reassurance and support of child and family, medication if needed and guidance and advocacy in relation to school achievements. The major goal of treatment is to help the child succeed in moving along the various lines of development. Clonidine, a centrally active alpha2-noradrenergic agonist is the first choice of medical treatment in most cases. If clonidine fails, pimozide and haloperidol are considered to be good alternatives. PMID- 2882619 TI - [Suggestion and recovery. A scientific approach to the suggestive experience of the recovery process]. PMID- 2882618 TI - Disorders in the system of cyclic nucleotides in atherosclerosis: cyclic AMP and cyclic GMP content and activity of related enzymes in human aorta. AB - Cyclic AMP and cyclic GMP content and activities of cyclic nucleotide metabolic enzymes were determined in intima and media of atherosclerotic and unaffected human aorta obtained shortly after death due to myocardial infarction. Cyclic AMP content in fatty streaks and atherosclerotic plaques was lower by three- and five fold, respectively, as compared with uninvolved intima. Cyclic GMP level in atherosclerotic lesions was estimated to be three-fold higher than in grossly normal area. Basal activity of adenylate cyclase in fatty streaks and plaques was two- to six-fold lower than in unaffected intima. Besides, the ability of adenylate cyclase to be stimulated by the stable analogue of prostacyclin, carbacyclin, was suppressed in plaques. Guanylate cyclase activity in fatty streaks was 1.5- to three-fold higher than in normal tissue. The thiol-reducing agent, dithiothreitol, decreased the enzyme activity to normal level, suggesting the oxidative nature of guanylate cyclase activation in the lesion zone. There were no significant changes in cyclic AMP phosphodiestease activity in the regions of the atherosclerotic lesion. Cyclic GMP phosphodiesterase activity in atherosclerotic plaques was two-fold lower than in the intima of unaffected areas. We did not find differences in the content of cyclic nucleotides or related enzyme activities in the media of uninvolved areas of human aorta nor in the media underlying atherosclerotic lesions. Our findings suggest that development of human atherosclerotic lesions is accompanied by dramatic changes in the cyclic nucleotide metabolism featuring gradual hormonal receptor uncoupling from adenylate cyclase, activation of guanylate cyclase in fatty streaks and inhibition of cyclic GMP phosphodiesterase in plaques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882620 TI - Induction of metallothionein by steroids in rat primary hepatocyte cultures. AB - The purpose of this study was to characterize the induction of metallothionein (MT) by steroids in rat primary hepatocyte cultures. Comparison of the characteristics of MT induction by a steroid (dexamethasone) to that by metals (Zn and Cd), examination of the involvement of the glucocorticoid receptor in the steroid induction of MT, and determination of the potency and effectiveness of a number of steroids were studied. In general, the patterns of MT induction by metals and steroids were quite different. For metals, the maximal MT induction (12- to 39-fold) was limited by toxicity whereas for steroids, a plateau in MT induction (fivefold) occurred at noncytotoxic concentrations. Steroids elicited an increase in MT at concentrations that were one-hundredth to one-thousandth less than that of metals. A combination of metal and steroid increased the induction of MT to a level higher than achieved by metal or steroid alone. The effectiveness of steroids at inducing MT was related to their ability to induce a specific glucocorticoid effect, induction of tyrosine aminotransferase. For specific classes of steroids, synthetic glucocorticoids were more potent than the metals in inducing MT, but endogenous glucocorticoids, mineralocorticoids, androgens, and estrogens were less potent than the metals. The concentration of corticosterone, the major endogenous glucocorticoid of rats, required to induce MT in hepatocytes was 100 times higher than concentrations achievable in the plasma of rats. In conclusion, in rat hepatocytes dexamethasone was a more potent but less effective inducer of MT than Zn or Cd; synthetic glucocorticoids were more potent but endogenous adrenalcorticoids (i.e., glucocorticoids, mineralocorticoids, androgens, and estrogens) were both less potent and less effective inducers of MT than were metals, suggesting that glucocorticoids may not be the mediator for stress-induced MT induction; and induction of MT by steroids correlated well with the induction of tyrosine aminotransferase, supporting the involvement of a hormone-receptor complex in the induction of MT by steroids. PMID- 2882621 TI - Skeletal muscle glucocorticoid receptor and glutamine synthetase activity in the wasting syndrome in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - This study demonstrated specific changes in rat skeletal muscles after a single oral dose (100 micrograms/kg) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The development of the wasting syndrome was characterized by marked body weight loss, as well as atrophy of plantaris and gastrocnemius muscles. Fourteen days after administration of TCDD, gastrocnemius muscle cytosolic glucocorticoid receptor binding, measured at a single saturating concentration of [3H]triamcinolone acetonide, was significantly diminished, while plantaris muscle glutamine synthetase activity was strikingly elevated, indicating that specific biochemical alterations occur in skeletal muscle in the wasting syndrome. PMID- 2882622 TI - Renal damage induced by cadmium-metallothionein: effects on biochemical indicators. AB - Time dependent changes in urinary biochemical indicators for renal tubular injury and dysfunction were determined in female Wistar rats after an intraperitoneal injection of cadmium-metallothionein (Cd-MT) (50, 150 or 300 micrograms Cd/kg body wt) to further characterize the tubular damage caused by Cd. The Cd-MT injection caused dose-dependent increases in urinary activities of the enzymes (alkaline phosphatase; gamma-glutamyl transpeptidase; lactate dehydrogenase, LDH; N-acetyl-beta-D-glucosaminidase) on day 1, which appeared to reflect the tubular injury. The rate of increase in LDH, a cytosolic enzyme, was the largest among those of the enzymes. This result coincided with the data reported for repeated administration of ionic Cd to rats, suggesting that the feature of tubular injury caused by an injection of Cd-MT is similar to that by chronic exposure to ionic Cd. Changes in urinary glucose and total protein, indicators of tubular dysfunction, and metals (Cd, zinc and copper) were accompanied with those in urinary enzymes. Hydrocarbons in breath of rats injected with Cd-MT at a dose of 300 micrograms Cd/kg body weight were also determined as an indicator of in vivo lipid peroxidation. The levels of ethane and propane were significantly increased at 12 h after injection, which suggests that lipid peroxidation is partly involved in the tubular damage reflected by the increases in urinary enzymes. PMID- 2882623 TI - Proposed nomenclature for cytolytic toxins of sea anemones. PMID- 2882624 TI - [Immunoregulatory T-lymphocytes of patients with periodontal diseases in gastric and duodenal peptic ulcer]. PMID- 2882625 TI - [Patterns of deformity in bridge dentures made of metal]. PMID- 2882627 TI - [Risks associated with the use of short-acting benzodiazepines]. PMID- 2882626 TI - High-dose acetylsalicylic acid after cerebral infarction. A Swedish Cooperative Study. AB - Within 3 weeks of the event, 505 patients with cerebral infarction, minor or major stroke, were randomly assigned to treatment with acetylsalicylic acid (ASA) 1.5 g/day or placebo in a double-blind clinical trial with a follow-up of 2 years in all patients. Primary events were considered to be recurrent stroke or death; secondary events, myocardial infarction and transient ischemic attack. There was no difference in stroke recurrence rate in the ASA and placebo groups (12 and 13%, respectively), nor was there any significant difference in the rate of recurrent stroke or death, first event counted (23% in the ASA and 22% in the placebo group). The risk of transient ischemic attack and myocardial infarction was not reduced in the ASA group. In the present study there was no prophylactic effect of high-dose ASA after cerebral infarction. A compilation of the major trials of ASA after transient ischemic attack and cerebral infarction is presented. PMID- 2882628 TI - [Anomalies of the seminiferous system in cryptorchism]. PMID- 2882629 TI - Hyperplasia of spermatic cord nerves: a sign of testicular absence. AB - The comparative histologic study of the spermatic cord in the absence of testis, epididymis-testis separation, and normal development of both testis and epididymis, revealed that there is nerve trunk hyperplasia and hypertrophy in absence of the testis. This finding may greatly aid the diagnosis of testicular absence in the management of impalpable testes. PMID- 2882630 TI - Interstitial cystitis--1987. PMID- 2882631 TI - [Transmission of ATLV (HTLV-I) through blood transfusion]. PMID- 2882632 TI - [Hemorrhagic fever with a renal syndrome]. PMID- 2882633 TI - [Activity of enzymes of glutathione metabolism and regulation by cAMP in human tumors]. AB - Tumors were studied in 38 patients, tissues located far away from tumor being used as control. Breast and stomach tumors revealed relatively high levels of glutathione reductase, glutathione-S-transferase (I) and, particularly, gamma glutamyl transferase (II). The said changes were not observed in colorectal tumors. Gamma-glutamyl transferase (II) may be used as a marker for breast and stomach malignancies in man but it is not a universal and absolutely specific marker for all tumors. The activity of glutathione peroxidase (III) either did not change or decreased. The activating effect of cAMP on III and I remained generally unchanged in all tumors studied. PMID- 2882634 TI - [Several indices of immunocorrection in neurodermatitis patients]. PMID- 2882635 TI - [Various remarks with regard to the therapeutic management of patients with bronchial asthma in pregnancy]. PMID- 2882636 TI - [Inhibition of microsomal enzyme activity of the liver by various H2 receptor antagonists]. AB - The inhibition of 7-ethoxycoumarin deethylase activity by four different H2 receptor antagonists was studied using rat liver microsomes. The compounds tested represent two classes of H2-antagonists, i. e. structures with (cimetidine and oxmetidine) and without (ranitidine and SKF 93479) an imidazole ring. The microsomes were prepared from untreated and phenobarbital-treated animals. It was found that all four compounds, even those without an imidazole ring, inhibited deethylase activity. The compounds inhibited in the following order: SKF 93479 (90%) greater than cimetidine (58%) = oxmetidine (58%) greater than ranitidine (23%). In microsomes from phenobarbital-induced animals, the inhibitory activity of oxmetidine was increased 5-fold. Only the inhibitory potency of cimetidine was increased by preincubation of the H2-antagonist with the microsomes prior to the addition of the substrate. PMID- 2882637 TI - [Schizophrenic thought disorders. Identification of parameters of inferential processes for computer-assisted diagnostic findings in psychiatric diagnosis. I]. PMID- 2882638 TI - [The APUD system (structuro-functional organization, biological significance in health and pathology)]. PMID- 2882639 TI - [Regulatory role of T gamma and T mu-cells in the development of delayed-type hypersensitivity according to the results of skin tests and the clinical manifestations of furunculosis]. PMID- 2882640 TI - [Effect of alcohol on the rate of antipyrine biotransformation in the guinea pig]. PMID- 2882641 TI - Preproenkephalin B-derived opioid peptides in human phaeochromocytomas. AB - We demonstrated the presence and the secretion in vivo and in vitro of immunoreactive preproenkephalin B-derived opioid peptides (alpha-neoendorphin, dynorphin and leumorphin) in human phaeochromocytomas. In seventeen human phaeochromocytomas and two human adrenal medullas, the tissue contents of immunoreactive preproenkephalin B-derived opioid peptides (alpha-neoendorphin, dynorphin and leumorphin) and leu-enkephalin were studied by specific RIAs. Compared with a remarkable wide distribution in amounts of immunoreactive leu enkephalin (1063 +/- 437 pg/mg, mean +/- SE), small amounts of immunoreactive alpha-neoendorphin (22.6 +/- 6.4 pg/mg) and dynorphin (8.5 +/- 1.2 pg/mg) were detected in all seventeen human phaeochromocytomas and the two human adrenal medullas. Leumorphin-like immunoreactivity was detected in only four tumours. Gel chromatographic studies revealed the presence of preproenkephalin B-derived peptides and their high molecular forms. A significant positive correlation between the tumour tissue contents of immunoreactive alpha-neoendorphin and of dynorphin was observed. Nicotine (10(-5), 10(-4) mol/l) significantly stimulated the secretion of immunoreactive alpha-neoendorphin and dynorphin as well as leu enkephalin and catecholamines from cultured human phaeochromocytoma cells. Administration of 1 mg of glucagon to a patient with medullary phaeochromocytoma induced a rapid increase in the plasma concentration of immunoreactive alpha neoendorphin with a concomitant increase in plasma catecholamines. These results indicate the presence of preproenkephalin B-derived opioid peptides in human phaeochromocytomas and human adrenal medullas and their secretion in human phaeochromocytomas. PMID- 2882643 TI - Sulphasalazine and sulphapyridine serum levels in children to mothers treated with sulphasalazine during pregnancy and lactation. AB - Serum concentrations of sulphasalazine and sulphapyridine were measured during the first week of life in 15 children whose mothers had been on sulphasalazine during pregnancy. The serum concentrations of sulphapyridine and sulphasalazine were similar in the children and their mothers at delivery. The elimination rate of the drugs in the newborn children was slow but the concentrations were not so high that a bilirubin displacing effect could be expected. In eight mothers who were breast-feeding and taking sulphasalazine, analyses were done of mothers' serum, breast-milk and serum from their children. The results showed that the amount of sulphasalazine and sulphapyridine transferred to the child via the breast-milk is negligible with regard to the risk of kernicterus. It is concluded that a woman in need of sulphasalazine treatment can continue the medication throughout pregnancy and lactation without risk of development of kernicterus in her child. Only term infants without haemolytic disease were included in the study. Thus our conclusion is not necessarily valid for the prematurely born child or the child with haemolytic disease. PMID- 2882642 TI - Patient-controlled analgesia with piritramid for the treatment of postoperative pain. AB - Patient-controlled analgesia (PCA, intravenous self-application of narcotics) was studied during the early postoperative period. Subjects were 40 ASA I-III patients recovering from elective major and minor surgery (20 each having undergone abdominal or orthopedic operations). Whenever the patients required pain relief, piritramid demand doses of 2.0 mg were given via the hand-button of a microprocessor-controlled injection pump (On-Demand Analgesia Computer, ODAC). Hourly maximum dose was set to 15 mg with a pump refractory time of 1 minute between valid demands. A continuous low-dose piritramid infusion (0.24 mg/h) was additionally administered in order to prevent catheter obstruction. Duration of the PCA period was 19.7 +/- 6.5 hours (mean +/- SD). During this time, 17.1 +/- 13.8 demands per patient were recorded resulting in mean individual piritramid consumptions of 30.4 +/- 28.1 micrograms/kg/h. Self-administration was characterized by considerable intra- and interindividual variability. Following abdominal surgery, slightly more piritramid was needed compared with orthopedic patients, although less pain relief was achieved in the former group. The same proved to be true for a comparison between the sexes, males requiring significantly more piritramide for less pain relief than females (p = 0.05). Over all efficacy and patient acceptance proved to be excellent. Effectiveness of PCA was judged superior by about 73% of patients when compared with previously experienced conventional postoperative analgesia. Side effects (sweating, nausea, emesis) occurred in about 20% but were usually of minor intensity. No serious circulatory or respiratory problems were observed during the PCA period. Patient controlled analgesia is discussed as a promising concept for the treatment of acute pain and for clinical pain research. PMID- 2882645 TI - Antihistaminic and anticholinergic activity of amidine sulfides. PMID- 2882644 TI - Toxins, putative cell adhesins and fibronectin binding properties of Salmonella dublin. AB - Fifty Salmonella dublin strains isolated from cattle and human diarrhoeal cases were assayed for toxin production, haemagglutination, cell-surface hydrophobicity and fibronectin-binding properties. Most strains (65% of tested) produced cytotonic toxins and cytotoxic factors when tested on Chinese hamster ovary (CHO) cells and rabbit skin test. However, only three strains produced a skin permeability factor as determined in pig skin intra-dermal tests. None of the strains were positive in pig intestinal loop tests. Six of the 32 strains tested for 125I-fibronectin and its 125I-29 kDa N-terminal domain binding showed 10-17% and 6-10% binding, respectively. Most of the strains expressed mannose-sensitive haemagglutination (MSHA) (76%) and high cell-surface hydrophobicity (74%) when grown at 37 degrees C. At 20 degrees C the expression of MSHA and especially the expression of high cell-surface hydrophobicity were reduced. Twelve strains grown at 37 degrees C did not haemagglutinate erythrocytes from five animal species used in this study, while six of these strains expressed high cell-surface hydrophobicity. Salmonella dublin strains isolated in Denmark appeared to express a higher frequency of fimbriae type 1 (MSHA) and a lower frequency of high cell surface hydrophobicity than the strains from external sources. PMID- 2882646 TI - Models for the experimental analysis of depression. AB - Numerous models of depression have been proposed by investigators to assist in understanding this common and complex disorder. Some of these models have been specifically created to reflect certain philosophical or theoretical aspects of depression thought to be important. Other experimental paradigms evolved into models of depression when certain similarities with depressed patients were observed. The label depression undoubtedly refers to many separate and independent disorders that happen to share some similar behavioral symptoms. Although no one model can be appropriate for all types of depression, the evaluation in depressed patients of hypotheses developed in the models may provide diagnostic clues that would assist in selecting the therapeutic intervention that is most appropriate for a particular patient. PMID- 2882647 TI - Effect of phenformin on the plasma somatostatin concentration in healthy persons. PMID- 2882648 TI - Somatostatin immunoreactive nerve elements in the rat small intestine: light and electron microscopic studies. AB - Somatostatin-containing nerve elements were identified by light and electron microscopic immunocytochemistry in the rat small intestine. Labelled nerve cell bodies were found in the submucous plexus. In the myenteric plexus and the mucosa, numerous somatostatin positive fibers were found. Labelled fibers were observed in the vicinity of blood vessels, close to the smooth muscle cell membrane and to the lamina basalis of epithelial cells. In both plexuses, there were many synapses between the labelled and unlabelled nerve elements. After transection of the nn. mesenteric some of the degenerated nerve fibers originating outside the wall of the small intestine contained also somatostatin immunoreactivity. These observations suggest that somatostatin nerves not only influence the blood flow, but participate in regulation of smooth muscle activity and, by the aid of their interneuronal synapses they have a regulatory or transmitter effect on the other intrinsic nerve elements. PMID- 2882649 TI - Stage specific embryonic carbohydrate surface antigens of primordial germ cells in mouse embryos: FAL (S.S.E.A.-1) and globoside (S.S.E.A.-3). AB - Immunodetections of carbohydrate surface antigens were carried out for SSEA-1 and SSEA-3. Using alkaline phosphatase for the detection of primordial germ cells these surface antigens were detected at the cell membrane and the cytoplasm of the germ cells at E 10. PMID- 2882650 TI - Effective drugs in preventing recurrent coronary events. I. Hospital phase. PMID- 2882651 TI - Modification of coronary-prone behavior and clinical application. PMID- 2882652 TI - Recommendations of the scientific councils of the International Society and Federation of Cardiology on risk reduction after myocardial infarction. PMID- 2882653 TI - Effective drugs in preventing recurrent coronary events. II. Late management. PMID- 2882654 TI - Muscle exercise, energy metabolism and blood lactate. PMID- 2882655 TI - The loose coupling mechanism in molecular machines of living cells. AB - For a bacterial flagellar motor driven by a proton flux, a loose coupling mechanism has been proposed in which the movement of the proton is indirectly and loosely coupled with the rotation of the motor. This mechanism assures the efficient and smooth conversion of both electrical and chemical potential energies of the proton of the same order as the energy of the thermal fluctuation. Loose coupling has been also assumed for the proton ATPase. A proton flux produces a rotational movement of protein molecules and this movement promotes the synthesis of ATP. In the proposed mechanism, the number of protons necessary for the synthesis of one ATP molecule is not an integer but varies depending on the environmental condition. In the case of muscle, the coupling between the hydrolysis of ATP and the shortening was found to be extremely loose. It is likely that molecular machines in living cells often adopt a loose coupling mechanism in which the chemical reaction and the physical cycle have not always a definite one-to-one correspondence. PMID- 2882656 TI - Investigation of genetic linkage in human families. PMID- 2882657 TI - Localization of 3'-nucleotidase and calcium-dependent endoribonuclease in the plasma-membrane of Trypanosoma brucei. AB - We have characterized a 3'-nucleotidase activity of T. brucei. The enzyme has a pH optimum of 8.7, is inactivated by chelating agents and stimulated by divalent cations. It is inhibited by Zn2+, Mn2+, pyrophosphate and the trypanocidal drug suramin for which it has a Ki of 3 microM. From cell fractionation experiments it is concluded that the enzyme is located in the plasma membrane. Alkaline 3' endoribonuclease is also located in the plasma membrane of T. brucei and this activity shares a great number of properties with the 3'-nucleotidase activity, including its sensitivity to suramin. The possibility that both 3'-nucleotidase and endonuclease activities are catalyzed by the same enzyme cannot be excluded. PMID- 2882659 TI - [Myxosporidians of freshwater fishes in Cameroon. I. New species of Myxidium Butschli, 1882]. AB - This work deals with the study of myxosporidians parasitizing freshwater fishes in Cameroon. Fishes belonging to four families are concerned: Cyprinodontidae, Distichodontidae, Cyprinidae and Mormyridae. Five new species of Myxidium, all inhabiting the gall-bladder of their hosts, are described and named. They are as follows: Myxidium birgii, M. camerounensis, M. petrocephali, M. nyongensis and M. brienomyri. We have paid particular attention to vegetative stages in distinguishing species. PMID- 2882658 TI - Freeze-fracture studies on the surface membranes of pleomorphic bloodstream and in vitro transformed procyclic Trypanosoma brucei. AB - The surface membranes of bloodstream long slender, short stumpy and culture procyclic stages of Trypanosoma brucei brucei were compared with respect to freeze-fracture electron microscopy, intramembrane particle (IMP) distribution and beta-hydroxysterol content as shown by the characteristic intramembrane lesions induced by the polyene antibiotic, filipin. Little difference was observed between IMP density of long slender and short stumpy form body membranes: IMP's were more abundant on the protoplasmic face (PF) than on the exoplasmic face (EF). The procyclic culture form body membrane showed an increased density of PF IMPs and a decreased density of EF IMPs over their bloodstream short stumpy form predecessors. Flagellar membrane fracture faces displayed higher IMP densities than body membrane fracture faces of the same trypanosome. The numbers of filipin-induced lesions (FIL) indicated an increased level of beta-hydroxysterols in the short stumpy forms relative to the level in the long slender bloodforms. FIL density was further increased in the body membrane of the procyclic culture form. FIL density was higher in the flagellar membrane than in the corresponding body membrane and FIL were excluded from flagellum to body attachment zones of the flagellar membrane of all stages. The polarity of the FIL in the surface membranes was reversed on transforming from bloodstream to culture procyclic stages. These observations indicate qualitative differences between the surface membranes of the three stages, independent of the presence or absence of the surface coat. PMID- 2882661 TI - Detection of protein kinase substrates in extracts of Onchocerca volvulus. AB - Extracts of Onchocerca volvulus were phosphorylated in the presence of (gamma 32P)ATP and Mg2+ by endogenous protein kinase activity and exogenous rabbit muscle catalytic sub-unit of the adenosine 3'5' monophosphate dependent protein kinase (E.C. 2.7.1.37). Sodium dodecylsulfate polyacrylamide gel electrophoretic analysis of the 32P-labelled extracts revealed at least seven (32P) phosphoproteins with apparent Mr of 92,000; 86,000; 40,000; 27,000; 26,000; 23,000 and 17,000. The phosphorylation of the components with apparent Mr of 23,000 and 17,000 was catalysed by both endogenous and exogenous protein kinases, whereas the other components required exogenous protein kinase for their phosphorylation. The endogenous protein kinase activity was inhibited by suramin and the heat-stable protein inhibitor of the adenosine 3'5' monophosphate dependent protein kinase. The (32P)phosphoproteins identified in this investigation are probably candidate regulatory molecules in O. volvulus; though their physiological functions remain to be determined. PMID- 2882660 TI - [Polymorphism of Schistosoma mansoni eggs in the Guadeloupe (French Antilles) focus: presence of S. rodhaini-like parasites?]. AB - A comparative study of egg morphology of Schistosoma mansoni carried out between 9 parasite populations from Guadeloupean foci demonstrates the existence of an intraspecific polymorphism. Three types of lateral spined eggs have been described and their relative proportions observed between populations are related to the participation of a wild host-reservoir (Rattus rattus) in the life cycle of the parasite. Eggs of schistosomes originating from urbanized foci where man plays the main role in the transmission are less polymorphic than those from sylvatic or mangrove foci where rats are involved in the parasite transmission dynamics. In some populations of murine schistosomes, the existence of eggs with an identical shape to those of experimental hybrids between S. mansoni and S. rodhaini suggests the presence of "S. rodhaini-like" parasites in certain foci of schistosomiasis from Guadeloupe. PMID- 2882662 TI - Colonization of the rectum of Triatoma infestans by Trypanosoma cruzi: influence of starvation studied by scanning electron microscopy. AB - The colonization of the different regions of the rectum of Triatoma infestans by a Trypanosoma cruzi strain (zymodeme I) originating from the same locality as the bugs was studied by scanning electron microscopy after different periods of starvation of the bugs. Throughout the first 16 weeks no changes in colonization pattern could be observed. Parasite density was always minimal at the midgut/rectal junction and highest on the rectal pads; it was at a similar level in the other three regions of the rectum. Twenty weeks after feeding, a proportion of the bugs had died and in the surviving larvae a decreasing colonization of the cuticle occurred. Nonetheless, despite other regions being flagellate-free, a residual T. cruzi population always remained attached to the rectal pads. No changes in the proportion of trypomastigotes to epimastigotes were observed as starvation progressed. PMID- 2882663 TI - The surface morphology of the midgut cells of Rhodnius prolixus Stal (Hemiptera: Reduviidae) during blood digestion. AB - The surface morphology of the midgut cells of Rhodnius prolixus is examined using scanning electron microscopy. Before feeding, the microvilli are devoid of any extracellular structures and can be observed in both fracture faces and surface views. By 3 days after feeding, patches of extracellular membrane layers are observed on the surface of the midgut cells and by 7 days the extracellular membrane layers form an incomplete sheet overlying the microvilli, such that the microvilli are no longer visible in surface view. At 15 days after the blood meal the membrane layers are well developed in the intestine forming a continuous sheet, while in the crop the layers are not as completely developed. The results complement previous studies on the midgut ultrastructure of R. prolixus. The extracellular membrane layers are thought to function as a peritrophic membrane, allowing the spatial separation of digestive processes. PMID- 2882664 TI - A strategy for the prevention of the transmission of Chagas' disease during blood transfusion. AB - Our strategy for preventing the transmission of Chagas' disease during blood transfusion is discussed. In addition, the possibility that the Peru, Sonya, Tulahuen and Y strains of Trypanosoma cruzi show varying sensitivities to a series of amphiphilic cationic drugs in vitro at 4 degrees C was investigated using a microscope lysis test. All 21 drugs tested at a concentration of 10(-3) M lysed Sonya bloodstream trypomastigotes, but Peru, Tulahuen and Y strains were affected by 17, 17 and 11 drugs, respectively. All four strains were most sensitive to the acridines; acranil, aminacrine and mepacrine. Although some variation was seen in their responses to certain drugs, no one strain was particularly insensitive to the series as a whole. The effects of gentian violet, maprotiline and mepacrine on the infectivity of Sonya trypomastigotes following incubation at 4 degrees C for 24 h were evaluated. Mepacrine, at a concentration of 2.5 X 10(-4) M greatly decreased the viability of trypomastigotes, while 10( 3) M concentrations of both maprotiline, mepacrine, and gentian violet (at low parasite densities only) apparently abolished all infectivity. Although the compounds we tested did not show a significant improvement over gentian violet, the compound currently used in some blood banks, other existing amphiphilic cationic drugs could be of use in preventing the transmission of Chagas' disease during blood transfusion. PMID- 2882665 TI - Production and evaluation of specific antisera against sera of various vertebrate species for identification of bloodmeals of Glossina morsitans centralis. AB - Specific antisera against sera of 46 species of vertebrates were prepared. The antisera to 21 Bovidae species were raised in goats except the antiserum to goat serum which was raised in sheep. The antisera to 3 Suidae species were produced either in domestic pigs or warthogs, while antisera to most of the other vertebrate species were raised in rabbits. The antisera were used in an enzyme linked immunosorbent assay (ELISA) to identify the source of bloodmeals ingested by teneral and non-teneral tsetse at different time intervals after feeding. The bloodmeal donors were identifiable in 100% of the teneral tsetse up to 40 h post feeding and in 87.5% in those tested up to 74 h post-feeding. Non-teneral tsetse digested the species-distinguishing bloodmeal components faster than the tenerals. Bloodmeals could be identified in 100% non-tenerals at 20 h post feeding but only 67.5% and 50% of the bloodmeals could be identified 40 h and 74 h post-feeding, respectively. The antisera were also able to identify mixed bloodmeals from closely related species. PMID- 2882666 TI - Use of procyclic trypanosomes for detection of antibodies in sera from vervet monkeys infected with Trypanosoma rhodesiense: an immunodiagnostic test for African sleeping sickness. AB - Uncoated procyclic culture forms of African trypanosomes were used in immunofluorescence and simple agglutination assays to detect antibodies in the sera of vervet monkeys infected with T. b. rhodesiense. Antibodies to procyclic surface antigens were found in sera from animals with active, untreated infections or sera taken soon after treatment with trypanocidal drugs. The antibodies were detectable within 7 days of infection. No specific antibodies were detected in sera prior to infection or long after drug cure. The results indicate that antigens expressed on the surface of procyclic culture forms of T. brucei spp. are useful for the detection of antibodies produced in response to infection with T. b. rhodesiense and may allow the development of a simple immunodiagnostic test for African sleeping sickness. In addition, the use of a form of the trypanosome of a different differentiation state from the infecting organism illustrates the utility of this approach for detection of antibodies to common antigens. PMID- 2882667 TI - Chemotherapy of field cases of East Coast fever using halofuginone lactate. AB - The chemotherapeutic effect of halofuginone lactate (Terit, Hoechst) was tested against natural pathogenic Theileria parva infections (East Coast fever, ECF) in 24 cattle. Halofuginone lactate, administered per os, 1.2 mg per kg b.wt and repeated after 48 h manifested a potent schizonticidal effect, observed between 5 and 11 days post treatment. Disappearance of erythrocytic forms (EF) took long, ranging from 6 to 34 days post treatment. Differences on efficacy between halofuginone lactate tablets and solution were not observed. The use of furosemide (Dimazon, Hoechst) to promote diuresis in pulmonary oedema and streptomycin sulphate for control of secondary pulmonary infections, as supportive therapy measures, enhanced recovery from ECF. A recovery rate of 96% was recorded. Relapses were not observed. PMID- 2882668 TI - Cyclical development of Trypanosoma brucei gambiense from cattle and goats in Glossina. PMID- 2882669 TI - Preoperative ultrasonography of the undescended testis. PMID- 2882670 TI - Effects of aortic valve replacement on blood pressure, neurohumoral regulation, and arrhythmias in patients with aortic stenosis. PMID- 2882671 TI - HB Q-Thailand-HB H disease in a Chinese living in Geneva, Switzerland: characterization of the variant and identification of the two alpha-thalassemic chromosomes. AB - Data on a 24-year-old Chinese male with Hb Q-Thailand-Hb H disease are presented. The hemoglobin variant was characterized by fast microprocedures, mainly by reverse-phase high-performance liquid chromatography. Gene mapping analyses identified the alpha-thalassemia-2, which is associated with the alpha-Q chain, as caused by a 4.2-kb deletion involving the alpha 2 globin gene, while the alpha thalassemia-1 anomaly was the common Southeast Asian type in which part of the psi zeta, the psi alpha, and the alpha 2 and alpha 1 globin genes are deleted. PMID- 2882673 TI - Use and abuse of controlled substances by pharmacists and pharmacy students. AB - The use of controlled substances by samples of pharmacists and pharmacy students in one New England state was surveyed. A questionnaire was sent in November 1984 to a sample of 510 pharmacists randomly selected from the membership list of the state's pharmaceutical association and to a sample of 470 students from the state's pharmacy schools; 76% and 67% of the eligible pharmacists and students responded, respectively. The questionnaire elicited information about the respondents' use of controlled substances for self-treatment and recreation, as well as the instrumental use of stimulants to enhance performance. Almost half of the pharmacists (46%) and two thirds of the students (62%) reported using a controlled substance at some time without a prescription; 19% and 41%, respectively, used one within the past year. Whereas students used the drugs most often for recreation (57% ever, 36% currently), use by pharmacists was more equally divided among self-treatment (29% ever, 13% currently), recreation (29% ever, 9% currently), and instrumental purposes (21% ever). The drugs most often used were marijuana, stimulants (especially cocaine by students), tranquilizers, and opiates. Drug use was generally limited in amount, but 18% of the pharmacists and 35% of the students who ever used a drug either became dependent or were at risk of drug abuse. Current drug use was most strongly associated with age, non attendance at religious services, student access, year in school, and citizenship. The findings of this study suggest the need for continued development of impaired pharmacist committees and drug abuse prevention programs for pharmacists and pharmacy students. PMID- 2882672 TI - Analysis of fetal intestinal enzymes in amniotic fluid for the prenatal diagnosis of cystic fibrosis. AB - Amniotic-fluid intestinal alkaline phosphatase activity, gamma glutamyltranspeptidase activity, and leucine-aminopeptidase activity were quantitated to assess their reliability for the prenatal diagnosis of cystic fibrosis. The results indicate that for each of these enzymes an arbitrary cutoff point could be chosen that would enable one to correctly predict the outcome for the majority of at-risk pregnancies. However, some false positives and false negatives occurred with each enzyme. To obtain optimal diagnostic discrimination, the three enzyme values obtained for each sample were combined into a single linear discriminant function that proved to be a more accurate indicator of the outcome of the pregnancy. This was especially important for those cases in which the predicted outcome as based on the individual enzyme results was in disagreement. From the cases studied here, it appears that this method can be expected to give a correct prediction in approximately 96.5% of all 25%-at-risk pregnancies. False positives can be expected in approximately 1.4% of the pregnancies and false negatives in approximately 2.2%. PMID- 2882674 TI - Immediate and long-term pathophysiologic mechanisms underlying the genesis of sudden cardiac death in patients with congestive heart failure. AB - Congestive heart failure is the most important predisposing factor to the occurrence of sudden death in patients with cardiovascular disease. As left ventricular dysfunction deteriorates and symptoms of heart failure become evident, ambulatory ventricular arrhythmias become increasingly frequent and complex, and sudden cardiac death becomes an increasingly common occurrence. When the left ventricular ejection fraction has declined to less than 30 percent and symptoms of heart failure become refractory to treatment with digitalis and diuretics, 35 to 50 percent of patients will die of a lethal cardiac arrhythmia within three years. A number of factors interact to determine the occurrence of malignant ventricular arrhythmias in patients with congestive heart failure. Myocardial fibrosis and enhanced left ventricular wall stress may alter the electrophysiologic properties of the myocardium, but these factors may not be sufficient to explain the development of lethal rhythm disturbances. Neurohormonal activation may exacerbate the frequency and complexity of ambulatory arrhythmias in these patients, but such activation can persist for long periods without fatal electrophysiologic sequelae. Recent investigations suggest that electrolyte depletion may provide an important immediate precipitating cause for the occurrence of fatal ventricular tachyarrhythmias in the patient with severe left ventricular dysfunction whose susceptibility is markedly heightened by preexisting structural, hemodynamic, or neurohormonal factors. Further work is needed to determine if prophylactic therapy directed at preventing electrolyte depletion can favorably modify the long-term outcome of these severely ill patients. PMID- 2882676 TI - Hyperparathyroidism presenting as the first lesion in multiple endocrine neoplasia type 1. AB - In a study of 16 different families, 55 persons were considered to be affected by the syndrome of multiple endocrine neoplasia type 1 (MEN-1). Serum calcium measurements were available for all but six patients, long deceased, and hypercalcemia was invariably present. All but four of these patients have been subjected to surgery, and hyperparathyroidism was verified in each case. In all the patients studied, hyperparathyroidism was apparently the first manifestation of the MEN-1 syndrome. Pituitary tumors were detected in 23 patients, and there was evidence of pancreatic lesions in 32. Although either the pituitary or pancreatic manifestations dominated clinically in some patients, hyperparathyroidism was invariably present when sought. Measurement of serum calcium in asymptomatic relatives at risk for MEN-1 disclosed no case of hyperparathyroidism in children below the age of 18, whereas half of all screened persons between the ages of 18 and 30 were found to have hyperparathyroidism. In some, the serum calcium values were only marginally or even intermittently elevated. It is concluded that since hyperparathyroidism is apparently the first lesion in MEN-1, screening for this syndrome should primarily be directed toward the diagnosis of hyperparathyroidism. The temporal relationships suggest that hyperparathyroidism could be a prerequisite for the other types of endocrine neoplasms in the MEN-1 syndrome. PMID- 2882675 TI - Effects of antihypertensive treatment on cerebral perfusion. AB - Antihypertensive treatment reduces the risk of ischemic strokes and cerebral hemorrhage as complications of excessive or long-standing hypertension. However, neurologic dysfunction and brain damage may also accompany short-term, and under certain conditions, even long-term antihypertensive treatment. Therefore, treatment should be instituted restrictively and cautiously. Special regard should be given to the action of antihypertensive drugs on cerebral perfusion in patients with an increased risk for the development of treatment-induced cerebral ischemic complications, such as patients with hypertensive encephalopathy or autonomic dysfunction, and elderly patients with suspected sclerotic stenosis of cerebral or neck arteries. The structural and functional lesions of cerebral vessels observed in acute and chronic hypertension are reviewed, as are the effects of antihypertensive drugs on cerebral blood flow. Calcium channel blockers and angiotensin-converting enzyme inhibitors may have advantages as first-line drugs in the treatment of patients with an elevated risk of cerebral hypoperfusion, because of the selective action of these agents on vasoconstricted vessels and their differential effects in varying regional vascular beds. The excellent efficacy of these drugs in the short- and long-term treatment of hypertension may lead to changes in the traditional management of hypertensive emergencies as well as in management strategies for other patients at risk for treatment-induced complications. PMID- 2882677 TI - Rational approach to long-term use of H2-antagonists. AB - Although the approved indications for long-term histamine (H2) receptor antagonists are limited to the management of hypersecretory states and prophylaxis against recurrent duodenal ulcer, these agents are often prescribed indiscriminately. Definitive guidelines concerning proper patient selection for prophylaxis against duodenal ulcer recurrence are lacking. Persons likely to benefit from maintenance therapy include those who smoke and those with a long duration of symptoms or prior history of an ulcer complication. Although not an approved indication, maintenance therapy to prevent recurrent gastric ulcer is appropriate for elderly persons receiving nonsteroidal anti-inflammatory drugs or in patients with poor cardiopulmonary status who may not tolerate surgery for an ulcer-related complication. The role of long-term H2-antagonist therapy in reflux esophagitis is not defined but may be appropriate in scleroderma and Barrett's esophagus. Finally, several miscellaneous conditions, including cystic fibrosis, Menetrier's disease, and pancreatic exocrine insufficiency, may benefit from long term H2-antagonist therapy. Currently, clinical trials document the efficacy of maintenance therapy in duodenal ulcer for up to a three-year period; however, for gastric ulcer and chronic reflux esophagitis, the duration and benefit of long term therapy is not established, and treatment regimens need to be individualized. Therapy may be required indefinitely in the miscellaneous states mentioned previously. PMID- 2882678 TI - Systemic polyarteritis nodosa diagnosed at hysterectomy. AB - A 61-year-woman was referred because of declining general health. A diagnosis of uterine malignancy was suspected on the basis of uterine enlargement and an elevated erythrocyte sedimentation rate. Hysterectomy was performed, and histologic examination revealed necrotizing vasculitis affecting the ovaries, fallopian tube, and uterus. Muscle biopsy showed typical periarteritis nodosa lesions. Despite the scarcity of such cases, the incidental finding of necrotizing arteritis in a surgical uterine specimen warrants further investigation to determine if the vasculitic process is localized. PMID- 2882679 TI - Disparate hemodynamic responses to mental challenge after antihypertensive therapy with beta blockers and calcium entry blockers. PMID- 2882680 TI - Aryl sulfatase A deficiency in psychiatric and neurologic patients. AB - Two hundred ninety-five psychiatric and neurologic patients were randomly screened for aryl sulfatase A (ASA) activity in lymphocyte extracts. Two of these patients showed very low ASA activity, in the range of metachromatic leukodystrophy (MLD)-affected patients. The residual activity in these low ASA patients showed normal enzyme behavior with regard to ASA kinetic features and the ability to catabolize 14C labeled sulfatide by intact fibroblasts. Taking into account that approximately 3% of the general population are homozygous for the pseudo-aryl sulfatase A gene and are clinically unaffected, the data obtained here indicate that the patients studied in this work, as well as most psychiatric patients reported in the literature with low ASA activity, represent the normal ASA polymorphism. Thus, the very low ASA activity patients are in fact homozygous for the pseudo-deficient allele, which does not result in clinical abnormalities. The clinical symptoms in these psychiatric patients and probably other "variant" MLD patients are therefore not related to low ASA activity. PMID- 2882681 TI - Early postmarketing surveillance of betaxolol hydrochloride, September 1985 September 1986. PMID- 2882682 TI - Betaxolol in patients with glaucoma and asthma. PMID- 2882683 TI - Suppression of mitochondrial respiratory function after short-term anoxia. AB - Exposure of rat hepatocytes to 30 min anoxia resulted in a substantial decrease in O2 consumption on reoxygenation. Measurement of the sequestered Ca2+ pool of mitochondria by selective release with the protonophore, carbonylcyanide-p trifluoromethoxyphenylhydrazone (FCCP), and quantitation with the metallochromic indicator, arsenazo III, showed that anoxia caused a marked decrease in mitochondrial Ca2+. This loss could, in part, be due to decreased electrophoretic uptake resulting from a 20% decrease in the magnitude of the mitochondrial transmembranal potential. The decrease was associated with a decrease in ATP synthase activity as expected from the Ca2+ dependence of endogenous inhibitor binding to the ATP synthase. These results show that short-term anoxia suppresses mitochondrial function in hepatocytes and suggest that mitochondrial Ca2+ content may be important in this regulation. Regulation of the ATP synthase and other ion transport systems may provide a means to preserve ion distribution and protonmotive force and thereby prolong the period during which cells can tolerate anoxia. PMID- 2882684 TI - Two types of cells with central innervation in pineal gland of guinea pigs. AB - Cells within pineal glands isolated from young, male guinea pigs were impaled with intracellular microelectrodes and their responses to stimulate the nerve supply to the gland were studied. Two types of cells were identified. The response of cells of type I was a depolarization on which spikes were superimposed. Blockers of alpha-adrenoceptors abolished the spikes while beta adrenoceptor blockers reduced the depolarization to 27%, leaving a small tetrodotoxin-sensitive depolarization. After bilateral removal of the superior cervical ganglia (SCG) the beta-mediated depolarization was not observed while the spikes and the smaller depolarization persisted. The response of cells of type II was an initial large, transient depolarization followed by a smaller depolarization. Both components were reversibly blocked by tetrodotoxin. The only agents found to have any effect on these cells were oxytocin, vasopressin, and vasotocin. These peptides caused depolarization similar in amplitude to the larger response to nerve stimulation, although more prolonged. The large depolarization was not observed following ganglionectomy, but the smaller one persisted. It is concluded that cells of type I and II both receive inputs from nerves whose cell bodies lie in the SCG. Cells of both types are also innervated through another pathway. PMID- 2882685 TI - The cat: an animal model for studies of inactive renin. AB - Inactive renin, prorenin, is found in high concentrations in human plasma. We report herein the characteristics of trypsin-activated inactive renin from cat kidney and plasma. Cat and human plasma inactive renin were activated by similar concentrations of trypsin. As in humans, there was more inactive than active renin in cat plasma; also, inactive renin was low but detectable after nephrectomy. Trypsin-activated renal inactive renin, purified on Cibacron blue agarose and pepstatin-amino-hexyl-Sepharose chromatography, was inhibited by pepstatin and by a renin inhibitor similarly to cat and human active renins. The pH optimum of cat renin was biphasic: the higher peak of active renin was at pH 5.7, whereas that of activated inactive renin was at pH 7.5. As in humans, active and inactive plasma renin increased during sodium depletion and inactive renin increased during beta-adrenergic blockade, while active renin decreased. These results demonstrate that cat inactive renin is similar to human prorenin. Therefore, the cat may be a useful model for the study of prorenin. PMID- 2882686 TI - The pancreatic-adrenocortical-pituitary clamp technique for study of counterregulation in humans. AB - The present experiments were undertaken to develop an approach to analyze the contribution of individual glucose counterregulatory hormones in humans. For this purpose, 24 normal subjects were studied twice: once (control experiments) hypoglycemia was induced by subcutaneous infusion of insulin; and once [pancreatic-adrenocortical-pituitary (PAP) clamp technique] the spontaneous responses of plasma glucagon, growth hormone, and cortisol to hypoglycemia were prevented by intravenous somatostatin and oral metyrapone, respectively, and each hormone was infused at variable rates, which reproduced spontaneous changes in their circulating concentrations in the control experiments. Plasma glucose rate of decrease (0.052 +/- 0.003 vs. 0.06 +/- 0.003 mg X dl-1 X min-1), plasma glucose nadir (49.8 +/- 1.2 vs. 50 +/- 1.0 mg/dl), initial suppression of glucose production (0.22 +/- 0.01 vs. 0.23 +/- 0.01 mg X kg-1 X min-1), subsequent compensatory increase in glucose production (0.54 +/- 0.05 vs. 0.48 +/- 0.04 mg X kg-1 X min-1), and the increase in glucose utilization (0.45 +/- 0.05 vs. 0.42 +/ 0.05 mg X kg-1 X min-1) in PAP clamp and control experiments, respectively, were not significantly different and were significantly correlated. Changes in plasma alanine, lactate, free fatty acids, 3-beta-hydroxybutyrate concentrations were also virtually identical in the PAP clamp experiments and in control experiments. We conclude that the PAP clamp technique can faithfully reproduce the spontaneous hormonal and substrate responses to hypoglycemia and should be useful to assess the contribution of individual hormones during counterregulation by creating an isolated (total or partial) deficiency of a particular hormone without confounding compensatory changes in secretion of other counterregulatory hormones. PMID- 2882687 TI - Contribution of neurogenic and myogenic factors in the response of rat proximal colon to distension. AB - The response of the rat proximal colon to distension and drugs that interfere with intrinsic and extrinsic nerves was investigated in vivo (urethan anesthesia) and in vitro. Saline distension induced the appearance of a cyclic contractile activity that was slightly inhibited by atropine (ATRO) and enhanced by physostigmine. Hexamethonium increased the distension-induced motor activity. Topical tetrodotoxin (TTX), lidocaine, or procaine produced an increase in motility of the proximal colon. Isolated segments of the proximal colon exhibit a high-amplitude phasic contractile activity that was increased by stretching, transiently inhibited by ATRO, unaffected by hexamethonium, and increased by TTX. The effects of both ATRO and TTX were more evident at high- than low-resting tone. In the presence of ATRO plus guanethidine, field stimulation of the isolated rat proximal colon suppressed the spontaneous contractile activity of the preparations. These findings indicate that, in the proximal colon of urethan anesthetized rats, a tonic discharge of intramural nonadrenergic noncholinergic neurons suppresses the inherent myogenic contractile activity of the smooth muscle cells. Extrinsic nervous supply plays a subsidiary role in maintaining colonic motility. PMID- 2882688 TI - Paracrine regulation of gastric acid secretion by fundic somatostatin. AB - The isolated, luminally perfused mouse stomach was used to determine whether somatostatin cells located in proximity to parietal cells exert a paracrine influence on acid secretion. Acid secretion in response to histamine and pentagastrin was accompanied by a dose-dependent increase in somatostatin secretion. Incubation of the stomach with somatostatin antiserum (final dilution 1:100), but not with normal serum, augmented significantly basal and secretagogue stimulated acid secretion. The augmentation was most evident with submaximal stimuli (92 +/- 18%, P less than 0.01, with 15 microM pentagastrin and 160 +/- 6%, P less than 0.001, with 5 microM histamine) and least evident with maximal stimuli (30 +/- 12%, P less than 0.05, with 200 microM histamine). The acid response to submaximal field stimulation (10 V, 20 Hz, 0.5 ms), which was accompanied by an increase in somatostatin secretion, was also augmented by somatostatin antiserum (115 +/- 12%, P less than 0.01), whereas the response to maximal field stimulation (20 V, 20 Hz, 0.5 ms), which was accompanied by a decrease in somatostatin secretion, a typically cholinergic effect, was not augmented further. It is concluded that fundic somatostatin modulates the acid secretory response to paracrine (histamine), hormonal (gastrin), and neural (acetylcholine) stimuli and that cholinergic stimulation of acid secretion reflects both the direct effect of acetylcholine on the parietal cell and its ability to eliminate the paracrine restraint exerted by somatostatin. PMID- 2882689 TI - Electrical control activity of the lower esophageal sphincter in unanesthetized opossums. AB - We recorded lower esophageal sphincter (LES) pressure and myoelectrical activity concurrently from the esophagus, LES, stomach, and proximal small intestine in unanesthetized opossums. LES electrical activity was characterized by almost continuous, spikelike oscillations at 15-40/min, which were accompanied by minicontractions 5-15 mmHg in amplitude. Basal LES pressure, however, did not depend on electrical oscillations. The LES exhibited cyclic changes in pressure and electrical activity synchronous with gastric contractions associated with the migrating myoelectric complex (MMC). During phase I, the LES pressure was stable and its electrical activity showed continuous low-amplitude (less than 0.3 mV) oscillations at a rate of 20 +/- 2 per min. During phases II and III of MMC related gastric activity, the LES developed strong phasic contractions, while the electrical oscillations grouped into clusters with an increased rate (32 +/- 1 per min) and amplitude (0.4-0.8 mV), each cluster corresponding to a phasic contraction. Feeding, pentobarbital, and cholinergic blockade abolished MMC related LES activity and resulted in a steady rate of LES electrical oscillations. LES relaxation induced by swallows or esophageal balloon distention abolished the LES electrical oscillations. Increases in LES pressure induced by pharmacological and hormonal stimulation correlated with concurrent increases in the rate of electrical oscillations. We conclude that the opossum LES has a unique pattern of electrical activity that differs from the electrical activity recorded from smooth muscle elsewhere in the gastrointestinal tract. This electrical activity is a form of control wave associated with a minicontraction. Phasic LES contractions during the intestinal MMC cycle may result from an increase in the rate and amplitude of the LES electrical control waves and fusion of minicontractions. PMID- 2882690 TI - Vagal influence on gastroduodenal HCO3- secretion in the cat in vivo. AB - Gastric and duodenal secretions of HCO3- were studied simultaneously in chloralose-anesthetized cats. The adrenals were ligated, and the cervical vagal as well as the abdominal splanchnic nerves were cut. Gastric secretions of H+ and HCO3- were calculated from measurements of the pH and PCO2 in the luminal perfusate. A duodenal segment devoid of Brunner's glands and pancreaticobilary secretions was cannulated in situ and the alkaline secretion determined by continuous titration at luminal pH 7.4. Electrical stimulation in the distal direction for 10-15 min of the cervical vagal nerves resulted in a 6- to 10-fold increase in gastric H+ and in a 20-60% rise in gastric HCO-3 secretion. Duodenal HCO3- secretion increased by 65-155%. Gastric basal secretions of H+ and HCO3- were not affected by atropine or hexamethonium, but both agents inhibited basal duodenal HCO3- secretion. Hexamethonium abolished and atropine reduced the rise in all secretions in response to vagal nerve stimulation. Thus gastroduodenal mucosal HCO3- secretion is stimulated by vagal mechanisms involving action on nicotinic as well as on muscarinic receptors and possibly also noncholinergic neurotransmission. PMID- 2882691 TI - Processing of receptor-bound somatostatin: internalization and degradation by pancreatic acini. AB - We have previously demonstrated the presence of specific binding sites for somatostatin on plasma membranes from pancreatic acinar cells. In the present study we attempted to characterize the fate of receptor-bound 125I [Tyr11]somatostatin. Internalization of somatostatin was rapid (reaching a plateau at 20% of the cell-associated specific radioactivity) and temperature dependent. To follow the processing of bound somatostatin, acini were incubated with 125I-[Tyr11]somatostatin at 5 degrees C during 16 h then, after washing, incubated at 37 degrees C for 90 min in fresh medium. Surface-bound somatostatin decreased rapidly, whereas radioactivity increased in the cell interior and the incubation medium. Intracellular and membrane-bound radioactivity was mainly intact 125I-[Tyr11]somatostatin. Degradation occurred at the plasma membrane level and led to iodotyrosine production. After 15 min of incubation, 15% of the initially surface-bound 125I-[Tyr11]somatostatin was compartmentalized within the cell, mainly in the microsomal fraction. After 30 min, a significant increase in radioactivity appeared in the nuclear fraction. These results indicate that the major part of somatostatin cellular degradation takes place at the plasma membrane level. Within the cell, somatostatin is routed to the nucleus via particular fractions sedimenting with microsomal vesicles. PMID- 2882692 TI - Ontogeny of renal hemodynamic response to renal nerve stimulation in sheep. AB - The renal hemodynamic response to direct electrical stimulation of renal nerves was studied in conscious and chronically instrumented fetal (130-142 days gestation; term 145 days), newborn (7-12 days postnatal), and adult nonpregnant sheep. Renal nerve stimulation (RNS) produced a significant decrease in renal blood flow (RBF) velocity and a significant increase in renal vascular resistance (RVR) in all three groups of animals. The overall decline in RBF velocity and the overall rise in RVR was less pronounced in fetal than in adult sheep (P less than 0.05). Changes in RBF velocity and RVR using an RNS frequency of 16 Hz were -35 +/- 4 and 81 +/- 19% in fetal sheep, -61 +/- 10 and 374 +/- 128% in newborn lambs, and -84 +/- 12 and 540 +/- 94% in adult sheep, respectively. RNS during intrarenal infusion of the alpha-adrenoceptor antagonist phentolamine was associated with a significant increase in RBF velocity and decrease in RVR in both fetal sheep and newborn lambs, but not in adult sheep. Moreover, it was found that the rise in RBF velocity and the decrease in RVR associated with RNS during alpha-adrenoceptor antagonism were completely inhibited by intrarenal infusion of ICI 118,551, a beta 2-adrenoceptor antagonist and unaffected by either cholinergic or dopaminergic antagonists. Taken together, these results suggest that the overall renal vasoconstrictor response to RNS is age dependent. Furthermore, the present results demonstrate that, contrary to observations made in adult animals, RNS can produce renal vasodilation in immature animals that is mediated by beta 2-adrenoceptors. PMID- 2882693 TI - Role of dipeptidyl peptidase IV in uptake of peptide nitrogen from beta casomorphin in rabbit renal BBMV. AB - We examined the handling of radiolabeled beta-casomorphin, Tyr-Pro-[3H]Phe-Pro Gly, by rabbit renal brush-border membrane vesicles (BBMV). The uptake of radiolabel into the vesicles was Na+-independent, but an inward-directed H+ gradient stimulated the uptake. The H+ gradient-dependent uptake was further accelerated by an interior-negative membrane potential, but inhibited in the presence of a protonophore. Treatment of the membrane vesicles with diisopropylfluorophosphate (DFP) greatly reduced the uptake of the radiolabel. Control as well as DFP-treated vesicles exhibited H+ gradient-dependent Gly-Sar uptake. Unlabeled beta-casomorphin inhibited Gly-Sar uptake in control vesicles, but the inhibition was significantly reduced in DFP-treated vesicles. DFP inhibited the activity of dipeptidyl peptidase IV in these vesicles and there was a direct correlation between the activity of the enzyme and the capacity of beta casomorphin to inhibit Gly-Sar uptake. Many di- and tripeptides reduced the uptake of Gly-Sar and the uptake of radiolabel from beta-[3H]casomorphin to a similar extent. We conclude that beta-casomorphin is hydrolyzed by dipeptidyl peptidase IV and the products are transported into the vesicles by the H+ gradient-driven peptide transport system. This conclusion is supported by the results from the analysis of the incubation medium by high-performance liquid chromatography that showed rapid hydrolysis of the pentapeptide by brush-border membranes to di- and tripeptides. PMID- 2882694 TI - Hydrogen peroxide elicits pulmonary arterial relaxation and guanylate cyclase activation. AB - Hydrogen peroxide produces concentration-dependent relaxation of precontracted isolated bovine intrapulmonary arterial rings by a mechanism which is independent of the endothelium or prostaglandin mediators. Relaxant responses to hydrogen peroxide concentrations of up to 100 microM were markedly attenuated by the inhibitor of soluble guanylate cyclase activation, methylene blue (10 microM). Micromolar concentrations of hydrogen peroxide elicit time- and concentration dependent increase in arterial levels of guanosine 3',5'-cyclic monophosphate that are associated with decreases in force. Soluble guanylate cyclase activity is markedly activated by enzymatically generated hydrogen peroxide in a manner that is most closely associated with the concentration of catalase present in the assay, by a mechanism that is inhibited by superoxide anion and the inactivation of catalase. Our data are most consistent with the involvement of compound I, a species of catalase formed during the metabolism of peroxide, in the mechanism of guanylate cyclase activation. The nature of this mechanism of arterial relaxation suggests that it could contribute to the regulation of pulmonary vascular tone by oxygen tension. PMID- 2882695 TI - Effect of stimulation of afferent renal nerves on plasma levels of vasopressin. AB - Experiments were done in alpha-chloralose-anesthetized, paralyzed and artificially ventilated cats with vagus, cervical sympathetic, aortic depressor, and carotid sinus nerves cut bilaterally to investigate the effect of afferent renal nerve (ARN) stimulation on circulating levels of vasopressin (AVP). Electrical stimulation of ARN elicited a pressor response that had two components, a primary (1 degree) component locked in time with the stimulus and a secondary (2 degree) component that had a long onset latency and that outlasted the stimulation period. The 1 degree and 2 degree components of the pressor response were largest at stimulation frequencies of 30 and 40 Hz, respectively. Autonomic blockade with hexamethonium bromide and atropine methylbromide abolished the 1 degree component. Administration of the vasopressin V1-vascular receptor antagonist d(CH2)5VAVP during autonomic blockade abolished the 2 degree component. Plasma concentrations of AVP measured by radioimmunoassay increased from control levels of 5.2 +/- 0.9 to 53.6 +/- 18.6 pg/ml during a 5-min period of stimulation of ARN. Plasma AVP levels measured 20-40 min after stimulation (13.6 +/- 7.0 pg/ml) were not significantly different from control values. Plasma osmolality was not altered during the course of the experiment. These data demonstrate that sensory information originating in the kidney alters the release of vasopressin from the neurohypophysis and suggest that ARN are an important component of the neural circuitry involved in homeostatic mechanisms controlling arterial pressure. PMID- 2882696 TI - Worsening of Tourette's disorder due to neuroleptic-induced akathisia. AB - Of 100 patients with Tourette's disorder, six demonstrated unequivocal worsening after their neuroleptic doses were increased. Akathisia was described in the records of all six patients and seemed to be the cause of the deterioration. PMID- 2882697 TI - Treatment of a patient with an airplane phobia. PMID- 2882698 TI - Clonidine in benzodiazepine withdrawal. PMID- 2882699 TI - Beta-adrenergic blockers for aggressive behavior in schizophrenia. PMID- 2882700 TI - Opioid pharmacokinetics in relation to their effects. AB - The chemical structure of drug molecules determines their fundamental pharmacological properties by 'fit' to the receptor, but the physicochemical properties, particularly lipid solubility and fraction un-ionised, dominate in determining distribution in the body and the rate of access to the biophase containing the drug receptors. For example, fentanyl appears much more potent than morphine because similar effective biophase concentrations are achieved with much smaller doses. Pharmacokinetic and pharmacodynamic investigations of the relationships between dose and the time-courses of blood concentrations and pharmacological effects of opioid drugs have helped explain the commonly observed variability between patients and have been useful in deriving effective dosage regimens of opioids such as pethidine, morphine, fentanyl and methadone where blood concentrations are a determinant of pharmacological response and 'target' analgetic blood opioid concentrations have been identifiable. However, there are instances when blood opioid concentrations are not determinants of the analgetic response. Examples include opioids, such as buprenorphine, for which the drug receptor dissociation rate determines the duration of action, heroin which first has to be metabolised to become an agonist, pentazocine which is an agonist at some opioid receptors and an antagonist at others, and opioids placed intra spinally acting on receptors in the spinal cord. PMID- 2882702 TI - Opiate anaesthesia. AB - Current use of opioids in anaesthesia is reviewed with particular emphasis on the use of opioids in anaesthetic doses, techniques that recently have become popular in cardiovascular anaesthesia. A major benefit of opioid anaesthesia (particularly fentanyl) is the cardiovascular stability which obtains during induction and throughout operation, even in patients with severely impaired cardiac function. Anaesthetic doses of morphine are associated with a higher incidence of cardiovascular disturbances and other problems. Pethidine is unsuitable for cardiovascular surgery because of severe haemodynamic disturbances when high doses are given. Sufentanil and alfentanil may prove more suitable alternatives. High doses of opioids can reduce or prevent hormonal and metabolic responses to the stress of surgery. Even very large doses of fentanyl or its new analogues do not prevent marked increases in plasma catecholamine concentrations in response to cardiopulmonary bypass. The reduction in hormonal and metabolic stress response does not appear to continue postoperatively. PMID- 2882701 TI - Narcotic pharmacokinetics and dynamics: the basis of infusion applications. AB - Morphine, pethidine and fentanyl have similar pharmacokinetic profiles with moderately long elimination half-lives (3 to 4 hours), large steady-state volumes of distribution (2 to 4 l/kg), and high hepatic clearances (10 to 20 ml/kg/min). Alfentanil has a shorter terminal elimination half-life (1 1/2 hours) because of a decreased steady-state volume of distribution (0.5 to 1 l/kg). Physicochemical properties and blood:brain tissue solubility can explain the clinical differences in the rate of onset and dissipation of narcotic effect for these four narcotics. Morphine's low lipid solubility and limited rate of blood:brain barrier penetration results in the slow onset and dissipation of narcotic effect relative to pethidine or fentanyl. Alfentanil's lower blood:brain solubility results in the very rapid onset of narcotic effect when compared to fentanyl. All of the narcotics have a very steep blood concentration:narcotic effect curves. Thus, small changes of narcotic blood concentrations can have profound changes of narcotic effect. Finally, different degrees of perioperative stimuli result in different narcotic blood concentration requirements. Thus, narcotic infusion rates need be varied during surgical procedures to adjust for the varying opiate requirement. PMID- 2882703 TI - Opioids, hypnotics and muscle relaxants: an update on pharmacokinetics and techniques of administration. PMID- 2882704 TI - Epidural and intrathecal opioids. AB - Small doses of epidural and intrathecal opioids produce effective and prolonged analgesia postoperatively, although the quality of analgesia does not differ from when conventional routes are used. The different opioids differ only in the speed of onset and duration of action, and in the incidence of side-effects. 'Minor' complications such as nausea, vomiting, pruritus and retention of urine are relatively common. There is a small incidence of respiratory depression which is delayed for several hours after drug administration and which may be prolonged. It is commoner after morphine and after intrathecal administration, and is also associated with advanced age, concomitant use of other central depressant drugs, respiratory disease and large doses. Because of the potentially lethal nature of this complication, it is recommended that the epidural and intrathecal routes of administration are used only when patients can be closely and constantly observed postoperatively. PMID- 2882705 TI - Pain relief after surgery. AB - Relief of pain after surgery remains poor for the majority of patients. The pain is unpleasant, and is associated with arterial hypoxaemia, venous thrombosis, myocardial ischaemia and a more florid hormonal response to surgery. Regional analgesia, systemic, subarachnoid or extradural opioids and antiprostaglandin drugs are all used to treat pain after surgery. Systemic opioids are used usually, because regional and axial techniques are labour intensive and antiprostaglandin drugs ineffective. Opioids given orally undergo extensive first pass metabolism and intramuscular doses are absorbed unpredictably. Intravenous administration avoids both problems and excellent results have been obtained using Patient Controlled Analgesia devices, but these machines are expensive. A simple regimen suitable for application to large numbers of surgical patients is required. Continuous infusion of fentanyl 100 micrograms h-1 IV begun two hours before surgery and supplemented by a single bolus dose of fentanyl 100 micrograms IV provided an effective background of analgesia. PMID- 2882706 TI - The 'new' relaxants. A review of the clinical pharmacology of atracurium and vecuronium. PMID- 2882707 TI - An electrophoretic method for the determination of the proportion of gamma aminobutyric acid in a mixture of labeled neurotransmitter and its catabolites. AB - An electrophoretic method for the separation of gamma-aminobutyric acid (GABA) from its metabolites after GABA-transaminase attack is presented. The method is based on the fact that at neutral pH GABA has no net electrical charge, whereas its major metabolites, succinic acid and Krebs cycle intermediates, are negatively charged. The method appears to be especially suitable for evaluation of true-labeled neurotransmitter within the radioactivity which is found in synaptosomes after labeled GABA-uptake studies. PMID- 2882708 TI - Antinociceptive effects and spinal cord tissue concentrations after intrathecal injection of guanfacine or clonidine into rats. AB - In the present study, the antinociceptive effects of intrathecal injections of the alpha 2-adrenoceptor agonists clonidine and guanfacine in rats was determined to establish their dose-response curves. Spinal cord tissue concentrations were also determined in a separate group of animals. Guanfacine was found to be more potent than clonidine and had a considerably longer duration of action. Thus, whereas the analgesic effect of clonidine declined to baseline by 4 hr after injecting doses of up to 50 micrograms, guanfacine still showed a considerable effect 18 hr after injecting both 25 and 50 micrograms. With both compounds, concentration gradients existed within the spinal cord. In the experiments with guanfacine, the region in the spinal cord tissue with the highest concentrations 10 min after injection contained around 30 pmol/mg wet weight. At 3 hr, this figure was around 20 pmol/mg. With clonidine, on the other hand, the concentration decreased from the maximal level of 200 pmol/mg at 10 min to 10 pmol/mg at 3 hr. On all occasions, except 10 min after injecting clonidine, it was found that the maximal tissue concentrations for both drugs remained below the cervical spinal cord, i.e., the rostral spread was less than expected, especially with drugs with such a long duration of action. The present investigation demonstrates analgesic effects of both clonidine and guanfacine after intrathecal administration, with guanfacine proving more potent and longer acting; the difference in duration of action is probably attributable to differences in rates of elimination of the drugs from spinal cord tissue. PMID- 2882709 TI - Congenital long QT syndrome: changes in QT interval during anesthesia with thiopental, vecuronium, fentanyl, and isoflurane. PMID- 2882710 TI - Intubating by sense, not dollars. PMID- 2882712 TI - Evaluation of gamma-glutamyl transpeptidase-to-creatinine ratio from spot samples of urine supernatant, as an indicator of urinary enzyme excretion in dogs. AB - gamma-Glutamyl transpeptidase activity was measured accurately in canine urine supernatant without gel filtration and was relatively stable at 4 C for at least 4 days after collection. The urinary gamma-glutamyl transpeptidase-to-creatinine ratio in spot samples was simple and quick to measure and was correlated with the 24-hour enzyme excretion. However, the usefulness of this ratio may be limited by within-day variation, and a questionable theoretical basis for its validity. PMID- 2882711 TI - Cyanide poisoning from metal cleaning solutions. AB - We report two cases of cyanide poisoning from accidental ingestion of an imported metal cleaning solution used by some Southeast Asians for shining coins. Both patients received specific therapy and recovered completely after a dramatic sequence of sudden collapse and severe cardiovascular compromise. PMID- 2882713 TI - [Laparoscopy in pediatrics]. AB - Laparoscopy has been performed in 68 infants and children. In 50 cases of non palpable testis; 7 cases of liver diseases; 4 cases of abdominal trauma; 7 cases for various other indications. In our experience, laparoscopy was a considerable advantage in the diagnosis and management of a number of pediatrics disorders. PMID- 2882714 TI - [Extravascular and perivascular granulomas and necrotizing vasculitis associated with hepatitis B antigen in the blood]. AB - The case of a patient with periarteritis nodosa-type necrotizing vasculitis and peri- and extra-vascular granulomas associated with hepatitis B virus surface antigenemia (HBs Ag) is reported. The association of necrotizing vasculitis and hepatitis B virus antigenemia is well documented but granulomatous extra-vascular lesions have not been reported in such circumstances. PMID- 2882715 TI - Linkage analysis between the beta-nerve growth factor gene and other chromosome lp markers and disseminated neurofibromatosis. PMID- 2882716 TI - Investigations on the neural crest. Methodological aspects and recent advances. PMID- 2882718 TI - Personality and suicide. PMID- 2882717 TI - Cerebrospinal fluid studies of bipolar patients with and without a history of suicide attempts. PMID- 2882719 TI - Suicide in schizophrenia. PMID- 2882720 TI - Suicide and alcoholism. PMID- 2882721 TI - Ethical considerations in biological research on suicide. PMID- 2882722 TI - [Pruritus: physiopathology. Therapeutic attempts]. PMID- 2882723 TI - [Study of electrophysiological effects of betaxolol]. AB - Betaxolol is a new cardioselective beta-blocker without any intrinsic sympathomimetic activity. A study of the cardiac electrophysiological effects of this molecule used intravenously was carried out in 20 patients. Betaxolol prolongs the sinus cycle (+ 25%, p 0.001), prolongs the sino-atrial conduction time (+ 20.1%) and atrio-hissian conduction time (+ 10.8%, p 0.001), and prolongs the refractory periods at all levels: atrial (+ 8%), nodal (+ 20.8%), right ventricular (+ 4.3%). These findings confirm the electrophysiological characteristic effects of the beta-blockers series; however, the moderate but significant increase of the refractory ventricular period, seems to provide this molecule with a certain degree of originality in this therapeutic class. PMID- 2882724 TI - Recombinant DNA and the clinics. PMID- 2882725 TI - How to find a mutation behind an inherited disease. AB - The search for the mutations causing human diseases is reaching new gene areas with increasing speed with new cloned genes or polymorphic gene areas, being reported every week. The almost 300 cloned genes and over 1000 RFLP-loci of the human genome can be used as tools to approach most human gene defects. Once the linkage between the disease and the RFLP has been found, chromosomal "jumping" or pulsed field electrophoresis can be used to separate the DNA areas in the neighbourhood of the first found RFLP locus for more detailed studies and finally for the location of the defective gene. Once found, the detailed analysis of gene mutations still requires the use of several, technically very demanding approaches of molecular biology. New techniques, such as the multiplication of the required gene area in a test tube as well as RNase protection assays have been used successfully to pick out about 80-90% of the mutations which occur in one gene area and cause the disease of this gene area. The increased specificity and sensitivity of these modern approaches do not, however, necessarily lead to the rapid diagnosis of all inherited diseases. Even once a linkage has been established between RFLP locus and a disease the path is still a long one: as demonstrated in Duchenne's muscular dystrophy and Huntington's disease, we have diagnostic RFLP-linkages but the search for the gene defect continues. Further, the increased sensitivity of the mutation assays will eventually reveal all the variations in an individual.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882726 TI - Molecular analysis of X-linked diseases. PMID- 2882727 TI - A recombinant DNA diagnostic program in practice. PMID- 2882728 TI - RFLPs in collagen loci and disease. PMID- 2882729 TI - Molecular genetic approaches to the analysis of inherited neurological disease. PMID- 2882730 TI - Proton transport by hepatocyte organelles and isolated membrane vesicles. AB - It is apparent that proton transport plays an important role in many essential hepatocyte functions. Important unanswered issues include the location of the H+ ATPase and its role in hepatic functions, the regulators of Na+-H+ exchange, the exact role of Na+-H+ exchange in bile formation and in hepatic regeneration, and the role of bile acids such as UDCA and nor-UDCA in mediating transepithelial proton transport. PMID- 2882731 TI - Effect of antibiotics on toxin production and viability of Clostridium perfringens. AB - We have recently reported (D.L. Stevens, K.A. Maier, B.M. Laine, and J.E. Mitten, J. Infect. Dis. 155:220-228, 1987) that clindamycin, rifampin, and tetracycline were more efficacious than penicillin in the treatment of fulminant gas gangrene in mice caused by Clostridium perfringens. We hypothesize that antibiotic efficacy correlated with bactericidal or toxin-suppressing properties of these agents. To investigate the possibility that penicillin is only bacteriostatic against C. perfringens, we performed macrobroth dilution MIC and MBC determinations using C. perfringens ATCC 13124. Mean MICs were equal to MBCs for the following antibiotics (micrograms per milliliter): clindamycin, 0.07; tetracycline, 0.05; rifampin, 0.03; metronidazole, 0.69; and penicillin, 0.27. The MIC/MBCs of chloramphenicol were 1.50/3.10 (micrograms/ml). Because antibiotic efficacy did not correlate with bactericidal activity, we measured alpha-toxin activity and found complete suppression of alpha-toxin activity by tetracycline, metronidazole, rifampin, clindamycin, and chloramphenicol at concentrations equal to the MIC. In contrast, alpha-toxin activity persisted at concentrations of penicillin equal to and above the MIC. The dynamics of bacterial killing and kinetics of alpha-toxin production were next studied in log phase cultures of C. perfringens with antibiotic concentrations 10 times the MIC. Clindamycin, metronidazole, and rifampin all caused rapid reductions in viability, turbidity, and alpha-toxin activity by 15 to 45 min. In contrast, penicillin demonstrated slower bacterial killing, increased turbidity (62.6% of control), and persistent alpha-toxin activity (80% of control values) for 2 h. Tetracycline and chloramphenicol were the least effective in reducing viability; however, the turbidity of cultures did not increase, and alpha-toxin activity was not detectable. Toxin suppression and rapid bacterial killing may in part explain the observed superior therapeutic efficacy of clindamycin, rifampin, and metronidazole compared with penicillin in the treatment of experimental gas gangrene. PMID- 2882732 TI - Comparison of single and combination antimicrobial agents for prevention of experimental gas gangrene caused by Clostridium perfringens. AB - The treatment of experimental gas gangrene caused by Clostridium perfringens was investigated by using combinations of antimicrobial agents. This study demonstrated that rifampin, penicillin, metronidazole, and clindamycin were all bactericidal against standard inocula (10(5) to 10(6) CFU). These antimicrobial agents were then administered to mice beginning 30 min after intramuscular injection of 10(9) CFU of C. perfringens type A. The highest doses used produced levels of drug in blood which exceeded the MIC by at least a factor of 40. In addition, other groups of mice received monotherapy at full dose or one-fourth full dose or combination antimicrobial therapy at full or one-fourth full dose. Among the single and combination antimicrobial treatments, metronidazole alone, clindamycin alone, and clindamycin plus penicillin were the most efficacious (P less than 0.05). Although the survival of mice treated with clindamycin plus penicillin was greater than that of mice treated with clindamycin alone, the difference did not reach statistical significance (P greater than 0.05). In contrast, mice treated with a combination of metronidazole and penicillin demonstrated greater mortality than those treated with metronidazole alone (P less than 0.05). In summary, combination antimicrobial therapy of experimental C. perfringens infection did not improve survival compared to that achieved with metronidazole or clindamycin alone, and some combinations significantly reduced survival (P less than 0.05). PMID- 2882733 TI - [Sinus dysfunction associated with catecholaminergic ventricular tachycardia. Therapeutic implications]. AB - The presence of resting sinus bradycardia (less than or equal to 45 bpm) with junctional escapes in an 8 year old child with catecholamine induced ventricular tachycardia, raised the problem of an underlying sinus node dysfunction. This was an important consideration bearing in mind the potential risk of the high dose betablocker therapy aggravating the sinus bradycardia. Electrophysiological studies showed pathological sinus node recovery times. Betablocker therapy did not aggravate the bradycardia, even after 6 months' treatment. A review of the literature showed the association of sinus bradycardia and catecholamine-induced ventricular tachycardia to be relatively common (39 p. 100). However, no mention was found of aggravation of this sinus bradycardia by betablocker therapy. PMID- 2882734 TI - [Neurohumoral factors and the vasomotor system]. PMID- 2882736 TI - Panic and avoidance in agoraphobia. Application of path analysis to treatment studies. AB - We explored a causal sequence between panic and avoidance to provide recommendations for psychotherapy, pharmacotherapy, and their combination in treating agoraphobia. We produced a two-way [( imipramine hydrochloride vs placebo] by [office-based behavioral therapy vs in vivo exposure]) design by amalgamating two studies. We assessed agoraphobic patients for panic and avoidance at these time points: baseline (week 0), midcourse (week 13), and termination (week 26). The causal sequence model was tested by path analysis. Imipramine was superior to placebo in lowering panic and avoidance at both postbaseline time points. Exposure was superior to office-based treatment in lowering avoidance only at week 13. Exposure appeared to produce quicker improvement of avoidance than office-based therapy, but relapse occurred if this improvement was not supported by medication. Exposure did not benefit panic. We believe patients should be informed that imipramine is superior to exposure in inducing a panic-free state. Exposure without imipramine is of benefit only in reducing avoidance, but adding imipramine to exposure is necessary for panic control and substantially improves exposure and exposure maintenance. PMID- 2882737 TI - [H2-Antihistaminics. 32. Synthesis and H2-antagonistic action of N-[3-(3 piperidino-methyl-phenoxy)propyl]-1,3,4-oxadiazole-2-amines]. PMID- 2882735 TI - Situational panic attacks. Behavioral, physiologic, and biochemical characterization. AB - To investigate the pathophysiology of nonpharmacologically induced panic attacks, 18 drug-free agoraphobic patients and 13 matched healthy subjects underwent structured exposure to phobic situations. Heart rate, blood pressure, and plasma free 3-methoxy-4-hydroxyphenylglycol (MHPG), cortisol, growth hormone, and prolactin levels were measured before, during, and after exposure. Fifteen patients experienced situational panic attacks during exposure. Panicking patients displayed significantly greater increases in heart rate but not blood pressure or plasma free MHPG or cortisol in comparison with the healthy subjects. Growth hormone and prolactin responses tended to be smaller in the patients. If brain noradrenergic hyperactivity occurs during situational panic attacks, it may be too brief or too restricted in regional localization to affect MHPG levels in plasma. Chronically recurrent attacks may cause an adaptation of neuroendocrine mechanisms activated by anxiety or stress. PMID- 2882738 TI - [14C-labeling of D 16,427, a new positive inotropic agent]. PMID- 2882740 TI - Towards a new leadership? PMID- 2882739 TI - Analyses of drugs by polarographic methods, XXVII. The polarographic behaviour of uldazepam. PMID- 2882741 TI - Advances in drug therapy for peptic ulcer disease. AB - Recently, three new drug types have emerged to treat peptic ulceration. We compared the mechanism of action of omeprazole and somatostatin-14, both inhibitors of gastric acid, with that of tetraprenylacetone, a drug thought to be cytoprotective in the upper gut. Omeprazole and somatostatin-14 caused potent inhibition of meal-stimulated acid secretion in the dog (92% +/- 6% and 97% +/- 1%, respectively). On the other hand, tetraprenylacetone had no significant inhibitory effect on acid secretion (4% +/- 17%). In separate studies, tetraprenylacetone was shown to be a stimulant of gastric bicarbonate secretion in the rabbit, increasing bicarbonate secretion from a basal level of 0 to 86 +/- 28 pmol/2 h. Tetraprenylactone was also found to be a strong stimulant of canine pancreatic bicarbonate secretion. The ability of tetraprenylacetone to stimulate endogenous bicarbonate secretion may explain its ability to heal ulcers both experimentally and clinically. PMID- 2882742 TI - [Neuromediator bioamines of the thyroid gland and structuro-functional aspects of its homeostasis]. PMID- 2882743 TI - [Apud cells and apudomas of the prostate, breast and uterus]. AB - Morphofunctional features of apud cells in the prostatic, mammalian and uterine parenchyma have been studied inadequately and their further comprehensive study is needed. It will help to estimate fully enough those pathologic changes in which apud cells are involved. Dyshormonal hyperplastic processes and, especially, tumours, are of greatest importance among them. It is essential to consider not only morphologic, but functional peculiarities of tumour tissue, that will enable one to study the biological activity, long-term results of reproductive organ apudoma treatment, as well as to solve the problem of their histogenesis sources. PMID- 2882744 TI - Preliminary injunction denied; curb on surgical assistants still pending. PMID- 2882745 TI - Marine envenomations. PMID- 2882746 TI - A viral etiology for Hodgkin's disease? AB - There have been numerous suggestive but inconclusive reports of a possible infectious etiology for Hodgkin's disease. The discovery of the causative agent of the adult T cell leukemia-lymphoma syndrome suggests that a similar agent to the human T cell leukemia-lymphoma virus may have a causal role in Hodgkin's disease. PMID- 2882747 TI - Relationship between RNA polymerase I activity and ornithine decarboxylase in rat liver tissues. AB - In order to examine the relationship between RNA polymerase I and ornithine decarboxylase (ODC), three lines of experiments were performed, with the following results. The glucocorticoid-induced increase of RNA polymerase I in rat liver nuclei was not abolished by administration of inhibitors of ODC synthesis and activity, namely 1,3-diaminopropane and 2-difluoromethylornithine respectively. Anti-ODC antibody did not cross-react with RNA polymerase I solubilized from rat liver nucleoli, indicating the absence of a common protein sequence in these enzymes. The ODC preparation which was treated with transglutaminase in the presence of putrescine could not stimulate the activity of RNA polymerase I in nuclei of liver and prostate. All these results suggest that the increases in ODC protein or activity are not a prerequisite to the increase in RNA polymerase I after hormonal or physiological stimuli, but rather that the increases in both enzymes are separate responses to the primary stimuli. PMID- 2882748 TI - Acute effects of starvation and treatment of rats with anti-insulin serum, glucagon and catecholamines on the state of phosphorylation of hepatic 3-hydroxy 3-methylglutaryl-CoA reductase in vivo. AB - The fraction of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase in the dephosphorylated (active) form in rat liver in vivo was measured after various experimental treatments of animals. Intraperitoneal injection of glucose (to raise serum insulin concentrations) into rats 4 h into the light phase (L-4) resulted in a transient (30 min) increase in the expressed (E)/total (T) activity ratio of HMG-CoA reductase without any change in total activity (obtained after complete dephosphorylation of the enzyme). Conversely, intravenous injection of guinea-pig anti-insulin serum into rats 4 h into the dark phase (D-4) significantly depressed the E/T ratio within 20 min. Intravenous injection of glucagon into normal rats at this time point did not affect the degree of phosphorylation of the enzyme, in spite of a 10-fold increase in hepatic cyclic AMP concentration induced by the hormone treatment. A 3-fold increase in the concentration of the cyclic nucleotide induced by adrenaline infusion was similarly ineffective in inducing any change in expressed or total activities of hepatic HMG-CoA reductase. However, when insulin secretion was inhibited, either by the induction of streptozotocin-diabetes or by simultaneous infusion of somatostatin, glucagon treatment was able to depress the expressed activity of HMG-CoA reductase (i.e. it increased the phosphorylation of the enzyme). Therefore insulin appears to have a dominant role in the regulation of the phosphorylation state of hepatic HMG-CoA reductase. In apparent corroboration of this suggestion, short-term 4 h food deprivation of animals before D-4 resulted in a marked decrease in the E/T activity ratio of reductase, which was not affected further by an additional 8 h starvation. By contrast, the total activity of the enzyme was not significantly affected by 4 h starvation, but was markedly diminished after 12 or 24 h starvation. Longer-term starvation also produced a chronic increase in the degree of phosphorylation of the enzyme. These results are discussed in relation to the role of reversible phosphorylation in the control of hepatic HMG-CoA reductase activity in vivo. PMID- 2882750 TI - Retinoblastoma--genetic insights into neoplasia. PMID- 2882751 TI - Stimulation of superoxide anion formation by the non-TPA type tumor promoters palytoxin and thapsigargin in porcine and human neutrophils. AB - The non-12-O-tetradecanoylphorbol-13-acetate (TPA) type tumor promoters palytoxin and thapsigargin provoked a respiratory burst in porcine and human neutrophils. The amounts of oxygen consumed and superoxide anion (O2-) produced were found to be stoichiometric. Concentrations of 6.5 X 10(-8) M palytoxin and 1.2 X 10(-6) M thapsigargin were required for half-maximal stimulation to 3 X 10(6) porcine cells/ml in Hanks' solution. Combinations of palytoxin and thapsigargin, and of one non-TPA type and one TPA-type tumor promoter, had synergistic effects in stimulating O2- formation in neutrophils, suggesting that these compounds activate the cells by different signal transduction mechanisms. PMID- 2882752 TI - Proteolytic processing of epidermal growth factor within endosomes. AB - Following binding to its plasma membrane receptor, epidermal growth factor is transferred into three biochemically distinct endosomal compartments in a temporal fashion prior to delivery to the lysosomes. During this migration, the ligand undergoes sequential proteolytic processing resulting in the removal of six amino acid residues from the carboxy terminus. Individual events in the processing occur in different endosomal compartments. Incubations conducted in the presence of methylamine result in the retention of the ligand in an early endosomal compartment and processing is limited to the removal of the carboxy terminal arginine residue. This identification of specific processed forms of radiolabeled epidermal growth factor within distinct endosomal compartments demonstrates the compartmentalization of the presumed proteases which may serve as biochemical markers for these endosomal populations. PMID- 2882749 TI - Collagen metabolism in fibrotic liver. Effects of concanavalin A and aggregated myeloma immunoglobin G. AB - We previously have shown [Takahashi & Kobayashi (1982) Hepatology 2, 249-254] that the administration of concanavalin A to mice with schistosomiasis caused liver collagen content to be reduced by 50%. Here we report the effects of concanavalin A and aggregated mouse myeloma IgG on liver lysyl oxidase activity and present further evidence concerning the possible mechanism by which the liver collagen content was decreased in infected-treated mice. The lysyl oxidase activity at 8 weeks after infection in both treated mice and untreated infected controls was about 28-fold greater than in the age-matched uninfected controls. The specific radioactivity of intracellular free [14C]proline, the rate of collagen synthesis, the ratio of collagenase-sensitive, protein-bound, hydroxyproline to proline of collagen and the intracellular degradation of newly synthesized collagen were similar in treated animals and in untreated infected controls. In contrast, the extracellular degradation of newly secreted collagen and the specific radioactivity of protein-bound [14C]hydroxyproline in the agent treated groups were about 2-fold greater than those in the untreated infected controls. These results suggest that the observed 50% decrease in content of liver collagen of mice treated with the agents apparently was due to the increased extracellular degradation of newly secreted collagen. PMID- 2882753 TI - Biological effect of anti-fucosyl GM1 ganglioside antibody on cyclic adenosine 3',5'-monophosphate production in FRTL5 rat thyroid cells. AB - Addition of specific anti-fucosyl GM1 antibody raised in a rabbit caused dose dependent inhibition of endogenous and thyrotropin (TSH)- or thyroid stimulating antibody-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production in cultured FRTL5 rat thyroid cells. Further, the antibody inhibited the cAMP increase induced by prostaglandin E1 and forskolin. However, anti-fucosyl GM1 antibody did not affect the binding of [125I]bovine TSH to solubilized porcine thyroid TSH receptor or to FRTL5 cells. In conclusion, fucosyl GM1 is one of the specific membrane components of thyrocytes and appears to be involved in adenylate cyclase stimulation or cAMP generation. Further, the biological effects of the ganglioside do not seem to be mediated by the TSH receptor, suggesting a post receptor mechanism. PMID- 2882754 TI - An anabolic state in the heart induced by arginine intubation. AB - Using rat heart perfusion, we found that an anabolic state can be induced with a medium which includes glucose, carnitine, branched-chain amino acids and arginine after arginine intubation at a dose of 250 mg/kg body weight. It showed diminished levels of glutamine, glutamate, branched-chain oxoacids and phenylalanine (a marker of heart protein metabolism) release, reflecting anabolic changes occurring in the myocardium. While ornithine intubation caused a catabolic state in which the release of alanine and glutamate was increased but phenylalanine release was unchanged. This anabolic state may be a useful model providing for myocardial protection. PMID- 2882755 TI - Comparative study of the effect of beta-blockers with different pharmacological properties on cholesteryl ester formation in mouse peritoneal macrophages. AB - The effect of three beta-blockers: non-selective (propranolol), beta 1-selective (metoprolol), and with intrinsic sympathomimetic activity (pindolol), was investigated on 14C-oleic acid incorporation into cholesteryl esters in mouse peritoneal macrophages. Incorporation of 14C-oleic acid into cholesteryl esters was reduced about 10-fold by propranolol at 10(-4) M while incorporation into triacylglycerols was only 30% decreased at the same concentration. Metoprolol and pindolol had no significant effect on 14C-oleic incorporation into cholesteryl esters or triacylglycerols. Finally, propranolol inhibited the acyl-coenzyme A: cholesterol-O-acyltransferase activity, measured in vitro on macrophages homogenates, while the other studied beta-blockers were ineffective. These results suggest that propranolol could antagonize cholesteryl ester accumulation by macrophages, one of the main processes involved in atherogenesis. PMID- 2882756 TI - Chemical and biological properties of acetyl derivatives of the hydroxylamino reduction products of metronidazole and dimetridazole. AB - Metronidazole and related 5-nitroimidazoles undergo reduction of their nitro group apparently to produce such reactive species as 5-hydroxylaminoimidazoles. To define the role of these species we have sought ways to prepare them by the catalytic reduction of metronidazole, dimetridazole and flunidazole. Although their respective 5-hydroxylaminoimidazoles were too unstable to be isolated directly, their O,N-diacetyl derivatives were isolable. Of these, the diacetyl derivative of the hydroxylamine derived from dimetridazole, O,N-diacetyl-1,2 dimethyl-5-hydroxylaminoimidazole (DiacDMH), was used for further study. DiacDMH was converted to its monoacetyl derivative, N-acetyl-1,2-dimethyl-5 hydroxylaminoimidazole (AcDMH), by enzymatic deacylation. Both DiacDMH and AcDMH were examined for bactericidal activity against such strains as Bacteroides fragilis, Clostridium perfringens, and Escherichia coli strain SR58, which are known to be sensitive to dimetridazole, as well as a variety of other bacteria. No bactericidal activity was detected, even in the presence of deacetylating enzymes. As the 5-hydroxylaminoimidazole itself could not be shown to form in these bacterial incubations, it remains uncertain whether or not the hydroxylamino functionality of a 5-nitroimidazole has bactericidal activity. PMID- 2882758 TI - Inhibitory effects of etoperidone on the spontaneous activity of brainstem neurones and their excitatory responses to some putative transmitters. AB - In this microiontophoretic study delta 2,1,2,4-triazolin-5-one [1,3-(4-m chlorophenyl-1-piperazinyl) propyl]-3,4-diethyl hydrochloride (etoperidone, ET, Staff) was applied on rat brainstem (medullary-pontine) reticular neurones to verify its effects on the spontaneous firing and neuronal responses to administrations of 5-hydroxytryptamine (5HT), noradrenaline (norepinephrine, NA), acetylcholine (ACh) and gamma-aminobutyric acid (GABA). ET was able to depress the spontaneous firing by a dose-dependent (for a current intensity range of 40 70 nA) local anaesthetic-like mechanism. At 75 nA a reduction in the amplitude of the action potentials occurred, partially due to a non-specific effect of ET. Repeated administrations of ET caused a progressive neuronal desensitization to the inhibition (tachyphylaxis). All the excitatory neuronal responses to ACh, 5HT and NA (interpreted respectively as nicotinic cholinergic, alpha-noradrenergic, 5HT3-serotonergic) were blocked by ET, while the inhibitory responses to 5HT, NA and GABA were not affected. The analysis of the results leads to postulate for ET a postsynaptic mechanism of action. PMID- 2882757 TI - Adrenal catecholamine metabolism and myocardial adrenergic receptors in streptozotocin diabetic rats. AB - Adrenal medullary function and myocardial adrenergic receptors were investigated in streptozotocin-treated diabetic rats. The animals were rendered diabetic by a single i.v. injection of streptozotocin (STZ, 65 mg/kg) and killed 60 days after treatment. Adrenal tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT) activities were increased by 52, 28 and 39%, respectively, in the STZ diabetic rats. In addition, adrenal concentrations of dopamine (+52%) norepinephrine (+46%), and epinephrine (+33%) were elevated significantly (P less than 0.05). Increased adrenal TH activity reflected an increased Vmax, but no change in Km. Receptor densities (Bmax), determined by [3H]prazosin and [3H]dihydroalprenolol binding, were decreased by 24 and 25%, respectively, in the myocardium of 60-day diabetic rats. Insulin induced chronic hypoglycemia in the STZ diabetic rats produced a marked increase in the adrenal TH concentration (Vmax, +65% or +225%, respectively), as compared to control or diabetic rats, without changes in the affinity (Km) for the substrate. These results suggest that the STZ diabetic rat has abnormalities of catecholaminergic function of the adrenal medulla and myocardial adrenergic receptors, which may contribute to the development and maintenance of many of the hemodynamic and metabolic defects described in this animal model of diabetes mellitus. PMID- 2882759 TI - Effects of new hypoglycemic agent 2-piperazinyl-4-methyl-amino-5-methylthieno [2,3-d]pyrimidine dihydrochloride hydrate. AB - The antidiabetic effects of 2-piperazinyl-4-methylamino-5-methylthieno [2,3 d]pyrimidine dihydrochloride hydrate (Compound-(I] were investigated in various animals and in various conditions. Compound-(I) is a new hypoglycemic agent structurally unrelated to sulfonylurea and biguanide. It produced dose dependent hypoglycemic effects (10-100 mg/kg) in rats and mice under fed, fasted and glucose tolerated states. However, it was ineffective in fasted guinea pigs even when given at 100 mg/kg. In normal fed rats and mice, hypoglycemic effects of Compound-(I) were estimated to be 3-19 times and 12-70 times more potent than tolbutamide and phenformin, respectively. Compound-(I) also produced hypoglycemic action in streptozocin diabetic rats and genetically diabetic KK mice. Especially, its hypoglycemic effect was observed at the dose as low as 3 mg/kg p.o. in KK mice. However, elevation of blood lactate was accompanied by lowering of blood glucose after oral administration of Compound-(I) in normal rats and mice and in streptozocin diabetic rats, while these effects were not observed in guinea pigs. In addition, plasma insulin significantly increased after administration of Compound-(I) in both normal and KK mice, while this increase in plasma insulin was not so prominent in fed rats. This elevation in plasma insulin might be produced by alpha 2-adrenergic antagonism at pancreatic B cell as Compound-(I) suppressed epinephrine induced hyperglycemia by elevating plasma insulin. In conclusion, Compound-(I) seems mainly to produce hypoglycemic action through extrapancreatic mechanism which increases blood lactate associated with anaerobic glycolysis or inhibition of gluconeogenesis. In addition, elevation of plasma insulin also might be responsible for hypoglycemic effects. PMID- 2882760 TI - Effect of age, body composition, and lipid solubility on benzodiazepine tissue distribution in rats. AB - Changes in body composition with age may alter tissue drug uptake and result in altered pharmacokinetics and pharmacodynamics. Four young, 4 middle-aged and 4 old Fischer-344 male rats were given a single intraperitoneal dose of alprazolam (2.5 mg/kg), diazepam (5 mg/kg) and triazolam (1.25 mg/kg) and sacrificed after 1 h. Diazepam, desmethyldiazepam, oxazepam, temazepam, alprazolam, and triazolam concentrations were determined in brain, kidney, liver, spleen, lung, heart, adrenal, muscle, fat and plasma by gas chromatography. Free fraction in plasma was determined by equilibrium dialysis. Drug uptake varied widely among tissues. Highest uptake ratios relative to free (unbound) drug in plasma were in adrenal (56-135), liver (35-116) and kidney (19-50). Free fraction in plasma varied from 0.13 for desmethyldiazepam to 0.30 for triazolam, and was unrelated to age. Tissue drug uptake relative to muscle, total plasma or free plasma concentration showed no significant variation with age or body habitus. In vivo fat uptake was highly correlated (R = 0.95) with in vitro octanol/buffer partition ratio. Muscle and fat were the largest quantitative drug storage sites, with total uptake explained by lipophilicity. Thus, age-related changes in body habitus and clearance do not alter tissue binding of benzodiazepines at distribution equilibrium. PMID- 2882761 TI - Clostridium pyoarthrosis following arthroscopy. PMID- 2882762 TI - [New aspects of pain therapy using opioids--theoretical background and practical conclusions]. PMID- 2882763 TI - Lack of cross-tolerance in mice between the stimulatory and depressant actions of novel anxiolytics in the holeboard. AB - CL 218,872, tracazolate and tofisopam are compounds that are believed to act at the GABA-benzodiazepine (BDZ) receptor complex in the CNS and that have anxiolytic properties in animals or in man. Doses of each drug were selected to elevate, or to depress, exploratory head-dipping and locomotor activity in the holeboard in mice, and the development of tolerance to these effects was investigated. As previously found with benzodiazepines, tolerance did not develop to the stimulant effects of low doses of these compounds after 10 days pretreatment with either a low (stimulant) or a high (depressant) dose of the same compound. When animals were pretreated with a low (stimulant) dose, tolerance did not develop to the depressant effects of a high test dose. Tolerance was observed only to the depressant effects of a high dose of a drug, and only when animals were also pretreated with a high dose. The results are compared with those obtained with benzodiazepines, and the ability of current theories of tolerance to account for the results is discussed. PMID- 2882764 TI - A new inhibitor of elastase from the sea anemone (Anemonia sulcata). AB - A proteinase inhibitor for elastases was isolated from extracts of the sea anemone Anemonia sulcata and purified to apparent homogeneity. The procedure comprises ethanolic extraction of the deep-frozen animals followed by gel filtration on Sephadex G-50 and by ion exchange chromatography on DEAE-Sephadex A 25 and SP-Sephadex C-25 and by hydroxylapatite chromatography. The slightly acidic inhibitor (isoelectric point 5.9) is a small protein consisting of 48 amino-acid residues without tryptophan and phenylalanine. The single chain molecule contains two methionines and no free sulfhydryl group but six cysteines presumably forming disulfide bonds. Reaction with cyanogen bromide abolishes the inhibitory properties. The inhibitor exhibits a rather narrow specificity for elastases. It strongly inhibits porcine pancreatic elastase in a permanent fashion with an equilibrium dissociation constant Ki of about 10(-10)M and somewhat weaker the elastase from human leucocytes with a Ki of about 10(-7)M. No obvious inhibition is observed of other serine proteinase such as bovine trypsin, bovine chymotrypsin, subtilisin from Bacillus subtilis and cathepsin G from human leucocytes when tested with synthetic substrates. PMID- 2882765 TI - Serum activities of dipeptidyl-aminopeptidase II and dipeptidyl-aminopeptidase IV in tumor-bearing animals and in cancer patients. AB - Serum activities of dipeptidyl-aminopeptidases (DAP) II and IV were measured in tumor-bearing animals and in patients with blood and solid cancers using highly sensitive and specific fluorometric methods. In mice with intraperitoneal or subcutaneous implantation of Ehrlich ascites tumor cells, serum DAP II activity was increased and serum DAP IV activity was decreased, resulting in a significant increase in the ratio of serum DAP II and DAP IV activities. The increase in the ratio of these two activities paralleled the size of the subcutaneous tumors. However, both serum DAP II and DAP IV activities were increased in rats with experimental hepatic cancer induced by 3'-methyl-4-dimethylaminoazobenzene, and the increase in the ratio of the two activities was not significant. In cancer patients, as compared with healthy subjects, serum DAP II activity was increased and serum DAP IV activity was decreased, the ratio of serum DAP II and DAP IV activities being markedly increased in cancer patients. Both serum DAP II and DAP IV activities were increased in patients with hepatic cancer as were those in rats with hepatic cancer, but the increase in DAP II was greater than that of DAP IV; thus the ratio of the two activities increased significantly. These data suggest that the increase of the serum DAP II/DAP IV ratio could be a biochemical index of cancer. PMID- 2882766 TI - Comparison of temazepam elixir and trimeprazine syrup as oral premedication in children undergoing tonsillectomy and associated procedures. AB - Temazepam 0.5, 1.0 and 1.5 mg kg-1 in an elixir formulation (Euhypnos Elixir), was compared with trimeprazine tartrate 3 mg kg-1 in a syrup (Vallergan Forte Syrup), as premedication in 220 children (ASA grade I) undergoing tonsillectomy and associated procedures. Each patient was randomly allocated to one of the four treatments. The administration was blind to the observers in theatre, recovery room and postoperative ward, who assessed each patient according to a total of 14 criteria. A modelling technique allowed account to be taken of the effects of concomitant variables (e.g. age and duration of anaesthesia) where appropriate. No statistically significant difference was found between the efficacy of the treatments. The only statistically significant differences were that temazepam was associated with more ectopic beats under anaesthesia (P = 0.03 or 0.002, depending on the test applied), more postoperative vomiting (P = 0.04) and more postoperative restlessness (P less than 0.0001). PMID- 2882767 TI - I.v. temazepam: theoretical and clinical considerations. AB - Two injectable forms of temazepam, in 90% propylene glycol or 40% salicylic acid, were studied in volunteers, and before surgery in healthy patients. The volunteers also received two forms (capsule and elixir) by mouth. The salicylate preparation was painful on injection and both i.v. formulations caused an unacceptably high incidence of venous thrombosis. Temazepam was detected in plasma earlier following the elixir preparation than the capsule. Plasma concentrations were similar following both injectable preparations. The potency of i.v. temazepam in inducing drowsiness in patients was much less than expected and doses greater than 0.6 mg kg-1 were required to produce adequate sedation. There was a significant reduction in thiopentone induction dose in patients receiving temazepam i.v. PMID- 2882768 TI - Antagonism of vecuronium-induced neuromuscular blockade with edrophonium or neostigmine. AB - Antagonism of vecuronium-induced neuromuscular blockade was attempted, at varying degrees of spontaneous recovery, with edrophonium 0.5 mg kg-1 or neostigmine 0.05 mg kg-1 in two groups of 20 patients. Neuromuscular blockade was monitored using a train-of-four (TOF) stimulation. Adequate antagonism of neuromuscular blockade, defined as a sustained TOF ratio of 0.7 or more, was attained in all 20 patients given neostigmine and in 13 out of 20 given edrophonium. Five of the remaining seven patients given edrophonium had shown three or less responses to TOF stimulation before antagonism. While the time to onset of the action of edrophonium (22 s) was not significantly shorter than neostigmine (26 s), the time taken to attain a TOF ratio of 0.7 was significantly shorter with edrophonium (67 s compared with 194 s with neostigmine). It is concluded that edrophonium 0.5 mg kg-1 does not consistently antagonize vecuronium-induced neuromuscular blockade, particularly if there are three or less responses to a TOF stimulation present before antagonism. PMID- 2882769 TI - Antagonism of vecuronium and atracurium: comparison of neostigmine and edrophonium administered at 5% twitch height recovery. AB - In 39 healthy patients antagonism, by neostigmine 0.07 mg kg-1 or edrophonium 0.8 mg kg-1, of neuromuscular blockade induced by vecuronium or atracurium, was compared. Reversal was attempted when the height of the single twitch (TH) had recovered spontaneously to 5% of the control value. The evoked responses, initially single twitch, then train-of-four (TOF) were observed until the TOF ratio was 70%. Induced recovery from TH 5% to 25% was shorter following edrophonium than following neostigmine with both vecuronium (P less than 0.05) and atracurium (P less than 0.05). The recovery indices and times until TH was 75% of control and until the TOF ratio was 70% were not different. The time from a TH of 75% to a TOF ratio of 70% was shorter following neostigmine than following edrophonium with both vecuronium (P less than 0.01) and atracurium (P less than 0.01). Edrophonium had a much more variable effect on vecuronium than on atracurium. These results show that although the onset of action of edrophonium was faster than that of neostigmine, this did not lead to a faster clinical recovery, and antagonism by edrophonium may be delayed in a number of patients if vecuronium is the neuromuscular blocker. PMID- 2882771 TI - Beta-adrenoceptor antagonists increase sinus arrhythmia, a vagotonic effect. AB - The influence of vagal and sympathetic efferent activity on sinus arrhythmia in man has been studied in six healthy subjects by administration of hyoscine butylbromide and/or various beta-adrenoceptor blocking drugs using a microcomputer-linked electrocardiogram system. Sinus arrhythmia was quantitated as the s.d. of the R-R interval. Sinus arrhythmia was almost abolished by hyoscine butylbromide irrespective of the absence or presence and nature of the beta-adrenoceptor blocking drug. Atenolol and metoprolol alone prolonged the mean R-R interval and increased sinus arrhythmia. Oxprenolol, a drug with modest partial agonist or intrinsic sympathomimetic activity (ISA), prolonged the mean R R interval to a lesser extent but had no effect on sinus arrhythmia. Xamoterol, which has high ISA, shortened the mean R-R interval but had no effect on sinus arrhythmia. These data yielded a non-linear relationship between sinus arrhythmia and mean R-R interval. Exaggerated sinus arrhythmia appears to accompany beta adrenoceptor blockade only in the absence of ISA when bradycardia ensues. These findings are consistent with the hypothesis that the exaggeration in sinus arrhythmia is due to a central vagotonic effect secondary to the action of the drugs in the periphery. Changes in R-R interval induced by the adrenoceptor blocking drugs were altered to some extent by vagal blockade. This observation is consistent with the hypothesis that changes in heart rate induced by such drugs are determined in part by a change in vagal tone. PMID- 2882770 TI - In vitro responsiveness of human asthmatic bronchus to carbachol, histamine, beta adrenoceptor agonists and theophylline. AB - Responses of human bronchial strip preparations to contractile and relaxant agonists were measured in preparations from non-diseased and from asthmatic lung obtained 3-15 h post-mortem. The potencies of carbachol and histamine were approximately two times less in asthmatic than in non-diseased bronchi. This was statistically significant for carbachol (P less than 0.05), but not for histamine (P greater than 0.05). These results clearly indicate that the bronchial hyperreactivity to airway spasmogens observed in asthma is exclusively an in vivo phenomenon not involving increasing sensitivity of bronchial smooth muscle. The potencies of the beta-adrenoceptor agonists isoprenaline, fenoterol and terbutaline were significantly reduced by 4-5 fold in asthmatic bronchi compared with non-diseased airways. In contrast, theophylline was equipotent in the two populations of airway preparations. Thus, it appears that severe asthma is associated with decreased bronchial smooth muscle beta 2-adrenoceptor function. PMID- 2882772 TI - A rest and exercise haemodynamic evaluation of a new cardio-selective beta adrenoceptor blocker celiprolol alone and in combination with nitroglycerine in ischaemic heart disease. AB - The symptomatic benefits of combining beta-adrenoceptor blockers and nitrates in angina pectoris are well recognised. Their actions on cardiac haemodynamics and volumes when combined have been poorly characterized. Accordingly this study investigated a new cardioselective beta-adrenoceptor blocking agent celiprolol and buccal nitroglycerine in 24 patients with angiographically documented coronary artery disease. Following a control period, with confirmed stable haemodynamics, three groups (n = 8/group) of prospectively matched patients, were studied following intravenous celiprolol (8 mg), buccal nitrate (10 mg) or their combination. Haemodynamics and left ventricular ejection fraction (nuclear probe) were determined following each intervention. The actions of each regimen on the haemodynamics of exercise-induced angina were compared by exercise testing in the control state and following each regimen. At rest, celiprolol did not alter haemodynamic parameters. Nitrate therapy reduced left ventricular filling pressure (pulmonary artery occluded pressure--PAOP) and volumes; the ejection fraction and heart rate increased. Combination therapy resulted in a highly significant reduction in left ventricular preload and afterload (PAOP and mean arterial blood pressure) at an increased left ventricular ejection fraction and reduced cardiac volumes; there was a trend to reduce cardiac double product (HR X SBP). During exercise celiprolol reduced systolic blood pressure, heart rate and cardiac index; systemic vascular resistance index increased. Nitrate therapy reduced blood pressure and PAOP, and increased ejection fraction. Combination therapy reduced all components of the triple product (heart rate, systolic blood pressure and PAOP) without affecting the other haemodynamic or radionuclide parameters. These data suggest improvements in cardiac function from the combination of celiprolol and nitrate therapy which were not achieved by either agent when used as monotherapy; they afford an interesting insight into the manner in which such widely utilised therapeutic modalities interact in coronary artery disease. PMID- 2882774 TI - The mechanism of the antihypertensive effects of ketanserin: a comparison with metoprolol. PMID- 2882773 TI - No effects on sleep of a histamine H1-receptor antagonist: temelastine. AB - Twelve volunteer poor sleepers of mean age 57 years took placebo on each of 3 consecutive nights, and temelastine 100 mg on 3 consecutive nights in a double blind balanced order study. Sleep in the EEG laboratory was unaffected by the drug. PMID- 2882776 TI - Effect of beta-adrenoceptor blockade on exercise-induced plasma catecholamine concentrations and their dissipation profile. AB - The time-course of plasma noradrenaline (NA) and adrenaline (A) concentrations and their dissipation profiles were examined concomitantly with heart rate changes after strenuous exercise in eight normal subjects receiving either placebo or carteolol, a beta-adrenoceptor blocker. Post-exercise NA concentrations declined with time in a biexponential manner, while A disappearance curves were apparently monophasic. Plasma NA concentrations and their peak value attained within 3 min after exercise were higher in the carteolol than in the placebo phase, whereas there were no significant differences in the first and second disappearance t1/2 between the two trials. The monoexponential t1/2 of A in the carteolol trial was significantly longer than in the placebo trial. Our results suggest that the dissipation profiles of catecholamines released by exercise appear to be affected by beta-adrenoceptor blockade. PMID- 2882775 TI - Relationships between heart rate and PR interval during physiological and pharmacological interventions. AB - The relationships between heart rates (HR) and corresponding PR intervals (PR) were studied in 12 healthy young subjects during rest, standing and graduated treadmill exercise to heart rates of 160 to 170 beats min-1 and during the infusion of isoprenaline to heart rates of 100 to 110 beats min-1. During exercise, PR diminished with increasing HR. Over the range of HR from 60 to 160 beats min-1 all 12 individual subjects exhibited negative linear correlations between HR and PR described by the equation: PR (ms) = -0.351 HR (beats min-1) + 176.7 for composite data. During isoprenaline infusion the PR interval also diminished with increasing heart rate. Over the range of HR from 60 to 110 beats min-1, 11 of the 12 subjects exhibited negative linear correlations between HR and PR described by the equation: PR (ms) = -0.582 HR (beats min-1) + 186.5 for composite data. The exercise model was used to study the indirect (or rate dependent) effects and the direct actions on atrioventricular conduction of beta adrenoceptor blocking drugs and calcium channel antagonists, alone and in combination, in three groups of healthy subjects. Control and placebo observations on HR and PR at rest, standing and during exercise in these additional subjects also exhibited individual inverse linear relationships between HR and PR. Following the administration of beta-adrenoceptor blockers, PR were prolonged more than expected at the HR observed. Rate-adjusted PR prolongation during exercise exceeded standing which exceeded resting, indicating greater beta-adrenoceptor blockade in atrioventricular nodal tissue than in sinoatrial nodal tissue at each level of activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882777 TI - Sequence comparisons of complementary DNAs encoding aequorin isotypes. AB - Aequorin is the Ca2+-activated photoprotein which participates in the bioluminescence from the circumoral ring of the hydromedusa Aequorea victoria. The nucleotide sequences of five aequorin cDNAs have been compared and shown to code for three aequorin isoforms. The cDNA AEQ1 contains the entire protein coding region of 196 amino acids. The other four cDNAs contain only 70-90% of the coding region and apparently code for at least two other isoforms whose amino acid sequences differ significantly from that encoded by AEQ1. The nucleotide sequences coding for the three isotypes differ at a minimum of 54 positions out of a total of 588 nucleotides necessary to code for apoaequorin. Of these nucleotide differences, 24 account for 23 amino acid replacements, substantiating the microheterogeneity observed during sequencing of purified native aequorin [Charbonneau, H., Walsh, K.A., McCann, R.O., Prendergast, F.G., Cormier, M.J., & Vanaman, T.C. (1985) Biochemistry 24, 6762-6771]. Comparison of the deduced cDNA translations with the native protein sequences suggests the loss of seven residues from the amino terminus during purification of aequorin from Aequorea. Aequorin rapidly extracted from the jellyfish using conditions to minimize proteolysis is shown to have a larger molecular weight than that of purified native aequorin. Escherichia coli expressed aequorin encoded by AEQ1 is shown to have the same molecular weight and isoelectric point as those of one of the isotypes rapidly extracted from Aequorea. PMID- 2882779 TI - Halobacterial glycoprotein biosynthesis. PMID- 2882778 TI - Catalytic and regulatory effects of light intensity on chloroplast ATP synthase. AB - The incorporation of water oxygens into ATP made by photophosphorylation is known to be increased markedly when either Pi or ADP concentration is lowered. The present studies show a similar increase in oxygen exchange when light intensity is lowered even with ample ADP and Pi present. The number of reversals of bound ATP formation prior to release increases about 1 to about 27 in the presence of dithiothreitol and to 5 in its absence. The equilibrium of the bound reactants still favors ATP at low light intensity, as shown by measurement of the amount of bound ATP rapidly labeled from [32P]Pi during steady-state photophosphorylation. Changes observed in the interconversion rate in the absence of added thiol are likely involved in the regulation of the dark ATPase activity in the chloroplast. The interconversion rate of bound ATP to bound ADP and Pi in the presence of thiol is about the same at low and high light intensities. This rate of bound ATP formation is not sufficient, however, to account for the maximum rate of photophosphorylation. Thus, when adequate protonmotive force is present, the rate of conversion of bound ADP and Pi to bound ATP, and possibly that of bound ATP to bound ADP and Pi, must be increased, with proton translocation being completed only when bound ATP is present to be released. These observations are consistent with the predictions of the binding change mechanism with sequential participation of catalytic sites and are accommodated by a simplified general scheme for the binding change mechanism that is presented here.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882780 TI - Reciprocal regulation of glutamine synthetase and carbamoylphosphate synthetase levels in rat liver. AB - In glucocorticosteroid-treated diabetic rats, glutamine synthetase enzyme levels in the liver are decreased 3-fold, whereas carbamoylphosphate synthetase enzyme levels are increased 2.3-fold. In addition, immunohistochemistry shows that under these conditions the distribution of carbamoylphosphate synthetase is expanded over the entire liver acinus, whereas that of glutamine synthetase is reduced to very few cells bordering the central (terminal hepatic) veins. Using a newly isolated cDNA complementary to rat liver glutamine synthetase mRNA, we show that this regulation is primarily effected at a pretranslational level. (For data on carbamoylphosphate synthetase mRNA levels, see De Groot et al. (1986) Biochim. Biophys. Acta 866, 61-67). Furthermore, hybridization studies show stimulatory effects of both glucocorticosteroids and thyroid hormone on the glutamine synthetase mRNA level. Attempts to localize glutamine synthetase mRNA within the liver acinus by selective destruction of the pericentral zone failed because of generally low levels of liver mRNAs after CCl4 poisoning. In contrast to the situation after birth, significantly higher glutamine synthetase mRNA/enzyme activity ratios in fetal rat liver point to the presence of additional post transcriptional control mechanisms before birth. These findings complement similar observations on carbamoylphosphate synthetase gene expression (De Groot et al. (1986) Biochim. Biophys. Acta 866, 61-67). PMID- 2882781 TI - Measurement of acetyl-CoA carboxylase activity in isolated hepatocytes. AB - An assay is described for acetyl-CoA carboxylase activity in isolated hepatocytes. The assay is based on two principles: The hepatocytes are made permeable by digitonin. 64 micrograms of digitonin per mg of cellular protein were most effective in exposing enzyme activity without a significant effect on mitochondrial permeability. Enzyme activity is measured by coupling the carboxylase reaction to the fatty acid synthase reaction. The advantages offered by this procedure over existing assays are: rapidity, no need to prepare cell extracts, absence of product inhibition, no interference by mitochondrial enzymes, useful in systems with bicarbonate buffers, and simple separation of radioactive substrate from labelled products. Using this coupled enzyme assay a good correlation was observed between changes in the activity of acetyl-CoA carboxylase and changes in the rate of fatty acid synthesis in hepatocytes as effected by short-term modulators. PMID- 2882782 TI - Analysis of 100 kDa polypeptides from coated vesicles of bovine brain: two dimensional tryptic and chymotryptic maps. AB - Two-dimensional peptide map analysis was used to determine the structural homology among the '100 kDa'-group of polypeptides. There are at least six distinct polypeptides whose apparent molecular weights are 116, 113, 111, 108, 105 and 100 kDa. The molar ratio of the '100 kDa'-group of polypeptides to three clathrin monomers (equivalent to one triskelion) is 1.2:1. There are three families of polypeptides in the '100 kDa'-group as determined by two-dimensional peptide map analysis. They are 116 and 113 kDa polypeptides, 111, 108, and 105 kDa polypeptides and 100 kDa polypeptide. However, all six polypeptides apparently show a series of homologous peptides. It is suggested that the 100-116 kDa polypeptides may bind to triskelions at the area of homology that is found in the 100-116 kDa polypeptides. PMID- 2882783 TI - Activation of purified soluble guanylate cyclase by arachidonic acid requires absence of enzyme-bound heme. AB - The mechanism by which arachidonic acid activates soluble guanylate cyclase purified from bovine lung is partially elucidated. Unlike enzyme activation by nitric oxide (NO), which required the presence of enzyme-bound heme, enzyme activation by arachidonic acid was inhibited by heme. Human but not bovine serum albumin in the presence of NaF abolished activation of heme-containing guanylate cyclase by NO and nitroso compounds, whereas enzyme activation by arachidonic acid was markedly enhanced. Addition of heme to enzyme reaction mixtures restored enzyme activation by NO but inhibited enzyme activation by arachidonic acid. Whereas heme-containing guanylate cyclase was activated only 4- to 5-fold by arachidonic or linoleic acid, both heme-deficient and albumin-treated heme containing enzymes were activated over 20-fold. Spectrophotometric analysis showed that human serum albumin promoted the reversible dissociation of heme from guanylate cyclase. Arachidonic acid appeared to bind to the hydrophobic heme binding site on guanylate cyclase but the mechanism of enzyme activation was dissimilar to that for NO or protoporphyrin IX. Enzyme activation by arachidonic acid was insensitive to Methylene blue or KCN, was inhibited competitively by metalloporphyrins, and was abolished by lipoxygenase. Whereas NO and protoporphyrin IX lowered the apparent Km and Ki for MgGTP and uncomplexed Mg2+, arachidonic and linoleic acids failed to alter these kinetic parameters. Thus, human serum albumin can promote the reversible dissociation of heme from soluble guanylate cyclase and thereby abolish enzyme activation by NO but markedly enhance activation by polyunsaturated fatty acids. Arachidonic acid activates soluble guanylate cyclase by heme-independent mechanisms that are dissimilar to the mechanism of enzyme activation caused by protoporphyrin IX. PMID- 2882785 TI - [Desensitization as a reflection of receptor-enzyme system inactivation during a reaction. Kinetic model of the process]. AB - The kinetic regularities of the processes occurring in the system: receptor adenylate cyclase complex under the effect of a hormone, an agonist or a neuromediator, were studied. Experiments with cell cultures revealed that the effector caused an impulse increase in cAMP and a decrease in the effector stimulated activity of the adenylate cyclase complex. The above effects were considered within the framework of a kinetic model which takes into account the enzyme complex inactivation in the course of adenylate cyclase synthesis. The data obtained permit to explain the physiological effect of desensitization of the receptor-enzyme system with respect to the effector action as a result of inactivation of this system in the course of the reaction. Possible molecular mechanisms of inactivation are discussed. PMID- 2882784 TI - [Formation of mevalonic acid, sterols and bile acids from [1-14C]acetyl-CoA and [2-14C]malonyl-CoA in the liver of rabbits with experimental hypercholesterolemia]. AB - The effect of cholesterol diet on the rate of mevalonic acid biosynthesis from 1 14C acetyl-CoA, 2-14C malonyl-CoA and the incorporation of these substrates into sterols and bile acids in rabbit liver were studied. Simultaneously, the activities of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and acetyl-CoA carboxylase and the biosynthesis of fatty acids from acetyl-CoA and malonyl-CoA were measured. Hypercholesterolemia was found to be concomitant with the inhibition of acetyl-CoA carboxylase activity only in cell-free (700 g) and mitochondrial fractions and slightly decreased the incorporation of acetyl-CoA and malonyl-CoA into fatty acids in the postmitochondrial fraction. The HMG-CoA reductase activity in all subcellular fractions except for the postmicrosomal one was inhibited under these conditions. A significant decrease of acetyl-CoA incorporation and an increase in malonyl-CoA incorporation into mevalonic acid in all liver fractions except for microsomal one were observed in rabbits with hypercholesterolemia. These data provide evidence for the existence of two pathways of mevalonic acid synthesis from the above-said substrates that are differently sensitive to cholesterol. Cholesterol feeding resulted in a decreased synthesis of the total unsaponified fraction including cholesterol from acetyl CoA, malonyl-CoA and mevalonic acid. The rate of incorporation of these substrates into lanosterol was unchanged. All the indicated substrates (acetyl CoA, malonyl-CoA, mevalonic acid) are precursors of bile acid synthesis in rabbit liver. Cholesterol feeding and the subsequent development of hypercholesterolemia resulted in bile acid synthesis stimulation, preferentially in the formation of the cholic + deoxycholic acids from these precursors. PMID- 2882786 TI - Lipogenesis in the brown adipose tissue of the fetal baboon. AB - The ultrastructural and lipogenic capacity of the white and brown adipose tissue (WAT and BAT) of 10 baboon fetuses (gestational age, 138-183 days) were studied. The axillary, interscapular and pericardiac sites had at least 50% brown fat cells while the retroorbital site contained white adipocytes only. Both WAT and BAT incorporated 3H2O and 14C-glycerol into lipids at similar high rates. The activities of enzyme acetyl CoA carboxylase and glycerokinase were higher than those reported in human BAT and comparable to these reported in rodent BAT under unstimulated conditions. It is concluded that in the fetal baboon adipose tissue is capable of considerable de novo lipogenesis and that, despite the differences in microscopic appearance, WAT and BAT have similar lipogenic potentials with respect to the parameters measured. PMID- 2882787 TI - Neuroleptic-induced parkinsonism in older schizophrenics. AB - The association of neuroleptic drug-induced parkinsonism (DIP) with factors related to brain structure and function are poorly understood. Twenty-one medicated schizophrenics over age 55 years were evaluated for parkinsonism, tardive dyskinesia, psychiatric symptoms, ventricular/brain ratio (VBR), and neuropsychological function. Sixteen (76%) of the patients had DIP, whereas 10 (48%) had tardive dyskinesia. Increased severity of parkinsonism was significantly associated with larger VBR and the severity of negative symptoms. Severity of parkinsonism predicted poor visual-spatial function, whereas negative symptoms were modestly predictive of impairment in both verbal ability and cognitive flexibility. These findings suggest that brain atrophy may be a risk factor for DIP. The pattern of cognitive dysfunction associated with DIP in this sample is similar to that found in idiopathic Parkinson's disease. Dopaminergic dysfunction may underlie the pattern of pathology described in this report. PMID- 2882789 TI - Bromocriptine in neuroleptic resistance. PMID- 2882788 TI - Positron emission tomography studies of basal ganglia and somatosensory cortex neuroleptic drug effects: differences between normal controls and schizophrenic patients. AB - Glucose metabolic rate in the basal ganglia, thalamus, and somatosensory cortex was examined in eight patients with schizophrenia before and after receiving neuroleptic medication. Basal ganglia metabolic rates were increased with medication: more on the right than on the left and more in putamen than caudate. The cortical anteroposterior ratio, an index of relative hypofrontality, was not affected by neuroleptics. The brain areas that were found to be altered by neuroleptics were selected for comparison between off-medication schizophrenics and controls. Metabolic rates in the basal ganglia tended to be low in patients with schizophrenia in comparison to 24 age- and sex-matched controls. PMID- 2882790 TI - Release of luteinizing hormone-releasing hormone (LHRH) and neuroactive substances in unanesthetized animals as estimated with push-pull cannulae (PPC). AB - In this report, we have reviewed recent information gathered by probing with a push-pull cannula (PPC) the in vivo activity of the suprachiasmatic nucleus (SCN), hypothalamus, and anterior pituitary gland of freely moving animals. In male and female rats, probing of the SCN with the PPC revealed distinct oscillatory patterns of 5-hydroxy indole-acetic acid (5-HIAA) output very much dependent on the position of the cannula. In males, it was also possible to demonstrate, for the first time, in vivo output of immunoreactive vasopressin (VP) most likely from the SCN. Interestingly, the output of VP was stimulated by local activation of probable 5-hydroxytryptamine (5-HT) terminals with 5 hydroxytryptophan (5-HTP), a precursor of 5-HT synthesis. Probing the hypothalamus of rats and rabbits revealed that the in vivo release of luteinizing hormone-releasing hormone (LHRH) (frequency and amplitude of the LHRH signal) can be altered by administration of estrogen to ovariectomized rats; in both species, progesterone stimulated the amplitude of the LHRH signal, but only when this steroid was infused in pulses--the physiological mode of circulating progesterone in the rat. Further, in male rabbits, pulses of progesterone did not stimulate LHRH release. Last, probing the anterior pituitary with the PPC revealed that a series of push-pull perfusions could be performed in the same animal under different experimental conditions for nearly 60 days of experimentation. It also resolved the apparent paradox that after castration, decreased instead of increased activity of the neural LHRH apparatus was noticed when the PPC was positioned in the hypothalamus. Moving the PPC to the anterior pituitary revealed that castration was accompanied by an increase in the amplitude and frequency of the LHRH signals arriving in the anterior pituitary of castrated male rats. This mode of operation of the LHRH pulse generator is clearly compatible with the mode of luteinizing hormone (LH) release in gonadectomized animals. Finally, based on these results, a hypothetical model of the operation of the LHRH pulse generator has been proposed. PMID- 2882792 TI - [Spectrum of reactivity of monoclonal antibodies against specific T-suppressors]. AB - Monoclonal antibodies (MoAb) against specific T-suppressors CI and C4 are characterized by their reactivity with normal lymphoid cells and some tumour cell lines cultivated in vitro. MoAb CI and C4 react with T and B cells from spleen and lymph nodes. The amount of CI and C4 T and B subsets are equal in the spleen (25-29%), while lymph node T-lymphocytes contain twice as much CI and C4 cells than B-lymphocytes (40 and 20%, respectively). In the thymus CI is expressed mostly on immature (cortical) thymocytes and C4--on the mature (medullary) thymocytes. CI is expressed on some T-lymphoma cell lines (BW 5147, EL4, LBRM33), but not on thymoma RDM4 and mastocytoma P815. C4 is not found on the above cell lines but is expressed on the intermediate filament of mouse and quail fibroblasts and in lymphoid cells. This cross-reactivity may result from the existance of similar determinants in cytoskeleton proteins and lymphocyte membranes or from the intermediate filament expression on T-suppressor cellular membranes, but not on other functional T subsets. PMID- 2882791 TI - [Prevention by alpha and beta adrenoreceptor agonists and lithium hydroxybutyrate of injuries to the endothelium of the rabbit aorta induced by catecholamines]. AB - The damage of endothelial cells and intercellular junctions caused by 10 microM epinephrine (E) and 10 microM norepinephrine (NE) has been observed in perfused rabbit aorta. Simultaneous perfusion of the rabbit aorta with E and NE induced marked endothelial injuries at very low drug doses (0.1 microM). Alpha- and beta adrenoceptor antagonists prevented the development of catecholamine-induced endothelial alterations. Lithium hydroxybutyrate partially prevented endothelial alterations caused by 10 microM epinephrine, but blocked completely morphological injuries caused by simultaneous perfusion of the rabbit aorta with 0.1 microM E and NE. PMID- 2882793 TI - Factor XII gene alteration in Hageman trait detected by TaqI restriction enzyme. AB - A cDNA for coagulation factor XII has been used to investigate the presence of gene lesions and restriction fragment length polymorphisms in two brothers with Hageman trait and their family. A TaqI polymorphic fragment has been found in the two propositi and in 11 members of the paternal lineage. This polymorphism, absent in the normal population, is correlated with the reduction of factor XII activity and enables the identification of heterozygous factor XII deficiency. Factor XII gene deletion as the cause of Hageman trait in this family has been excluded. A restriction map has been constructed, and the TaqI polymorphic site has been localized within the 5' portion of the gene. The mutation in the polymorphic site is probably the cause of the factor XII deficiency. Data suggest the presence of one factor XII gene per haploid genome. PMID- 2882794 TI - Detection of hemophilia A carriers using intragenic factor VIII:C DNA polymorphisms. AB - A DNA polymorphism for an Xbal site in intron 22 of the human factor VIII:C gene extends the utility of DNA methods for carrier detection in families segregating for hemophilia A. While the DNA polymorphism detected by a BclI site in intron 18 of the factor VIII:C gene was informative for 41% of females studied, the BglI/intron 25 polymorphism provided no additional information because of apparent linkage disequilibrium. In contrast, the Xbal intron 22 polymorphism was useful in 53% of women who were uninformative (homozygous) for either the BclI or BglI polymorphisms. Using the BclI/intron 18 and Xbal/intron 22 intragenic polymorphisms, we could provide highly accurate information for 68% of women we studied who were at risk for carriership. The carrier status of the remaining 32% could be determined utilizing the closely linked Taql/St14 DNA polymorphism. PMID- 2882795 TI - The effect of vasoactive agents on the contractions of the initial lymphatics of the bat's wing. AB - The effect of vasoactive agents on the spontaneous contractions of the initial lymphatics of the bat's wing was investigated. Initial lymphatic contractile frequency and pulsatile pressure were measured with the servo-null micropressure system. Norepinephrine, phenylepinephrine, isoproterenol, acetylcholine, histamine, serotonin, bradykinin, prostaglandin F2a, prostaglandin E2, indomethacin and ibuprofen were delivered to the immediate vicinity of the initial lymphatic by microinjection or iontophoresis. Only bradykinin produced changes in initial lymphatic contractions which were significantly different from control. The response to bradykinin was characterized by an increase in the frequency, strength or duration of the contraction. PMID- 2882797 TI - Brain ammonia metabolism in hexachlorophene-induced encephalopathy. PMID- 2882796 TI - T-helper phenotype chronic lymphocytic leukemia (Thp-CLL): characterization of an Italian case with particular biological findings. AB - A patient with Chronic Lymphocytic Leukemia (CLL) characterized by an expansion of helper phenotype mature T lymphocytes is here described. The phenotype of these cells was OKT3+, OKT4+, Leu 9+, 5/9+, OKT8-, Tac- and functional studies showed a strong helper activity on B cell differentiation; an "in vivo" presence of an IgG-lambda paraproteinaemia has been demonstrated. Cytogenetic studies showed multiple clonal, numerical and structural rearrangements which included a tandem t(14;14) (q11;32) translocation. Hybridization showed HTLV I related specific bands indicating the presence of exogenous sequences related to prototype virus but derived from a different Retrovirus (HTLV 1c). The clinical course was aggressive and unsuccessful treatments with various polichemotherapeutic protocols, associated with multiple leukaphereses, were performed. The authors underline that despite the morphological, immunological, biological and virological heterogeneity, the common feature of T-helper CLL is the inexorable clinical course which needs a new therapeutic approach. PMID- 2882799 TI - [Immunohistochemical localization of pancreatic endocrine cells in the hamster]. PMID- 2882798 TI - Long-term culture of fetal rat hepatocytes in media supplemented with fetal calf serum Ultroser SF or Ultroser G. AB - Fetal hepatocytes cultured in medium supplemented with fetal calf serum (FCS) or Ultroser SF do not maintain production of albumin or transferrin beyond one week of culture. When dexamethasone (10(-7) M) is present, secretion of albumin and transferrin can be extended to two weeks, however, levels are extremely low. By three weeks, neither plasma protein can be detected in the culture medium in either conditions of culture. In contrast, hepatocytes maintained in medium supplemented with Ultroser G continue to produce albumin and transferrin at high levels for the entire three week period of this study. The morphology of the cultures are different. In FCS and Ultroser SF supplemented medium there are many more fibroblast and epithelial-like cells and relatively fewer cells which are distinctly hepatocytes when compared with Ultroser G supplemented medium. The level of tyrosine aminotransferase, which is a dexamethasone inducible enzyme, is found to be much higher in Ultroser G cultures, with no further increase demonstrable by addition of dexamethasone. In contrast, dexamethasone induces the enzyme by about eight-fold in cultures maintained in FCS supplemented medium. Therefore it appears that Ultroser G already contains sufficient steroid activity to maximize the level of tyrosine aminotransferase. A comparison between Ultroser C and SF (steroid-free) suggests that the mixture of steroid and steroid derivatives in the G formulation must be important in the maintenance of differentiated functions of hepatocytes in culture. However, supplementation of FCS cultures with dexamethasone, which is known to be present in Ultroser G, does not allow hepatocytes to retain their differentiated functions over an extended period. Therefore it is concluded that other components besides dexamethasone must be important. PMID- 2882801 TI - Pharmacological characterization of binding sites identified in rat brain following in vivo administration of [3H]-spiperone. AB - [3H]-spiperone is commonly used to label dopamine receptors in vitro in brain tissue. However, spiperone also interacts with brain 5-hydroxytryptamine and noradrenaline receptors. In vivo, [3H]-spiperone has been used for identifying dopamine receptors in both animals and man but the nature of the sites identified is unknown. The in vivo administration of [3H]-spiperone to rats leads to a selective accumulation of radioactivity in the olfactory lobes, tuberculum olfactorium, nucleus accumbens, striatum, substantia nigra, hippocampus, frontal cortex and hypothalamus, when compared to the cerebellum. In vivo drug displacement studies suggest that the binding of [3H]-spiperone in these areas may be to dopamine, 5-HT or noradrenaline receptors. [3H]-spiperone in vivo mainly labels dopamine receptors in striatum, tuberculum olfactorium, hypothalamus, substantia nigra and olfactory lobes. However, in the frontal cortex and nucleus accumbens specific binding involves not only dopamine receptors but also 5-HT and/or noradrenaline receptors. Interpretation of in vivo studies in man using radioactive spiperone and its derivatives must take into account the fact that this ligand only labels dopamine receptors in some brain areas. PMID- 2882800 TI - The antianaphylactic action of histamine H2-receptor agonists in the guinea-pig isolated heart. AB - The effects of histamine and of H1- and H2-receptor agonists on the response to specific antigen were studied in isolated hearts taken from actively sensitized guinea-pigs. Histamine and H2-receptor agonists (dimaprit, impromidine) dose dependently decrease the positive chronotropic and inotropic effects, and the severity of arrhythmias evoked by the challenge of sensitized hearts with specific antigen. Nordimaprit and the selective H1-receptor agonist 2-pyridyl ethyl-amine (2-PEA) did not modify the patterns of cardiac anaphylaxis. The positive inotropic and chronotropic responses of the isolated heart to exogenous histamine appear to be partly reduced in the presence of dimaprit. The H2 receptor agonists decrease the amount of histamine released during cardiac anaphylaxis which is increased by cimetidine, while nordimaprit and PEA were ineffective, indicating an inhibitory function afforded by H2-receptors in cardiac anaphylaxis. PMID- 2882802 TI - Examination of the mechanisms involved in tetanic fade produced by vecuronium and related analogues in the rat diaphragm. AB - The effects of vecuronium (Org NC45), Org 7678 and Org 7684 were examined on twitches and tetani recorded from rat isolated diaphragms. Org 7678 and Org 7684 exhibited approximately one tenth of the neuromuscular blocking potency of vecuronium. At concentrations producing equivalent amounts of twitch block, Org 7684 produced significantly less tetanic fade than did vecuronium or Org 7678. In cut muscles both vecuronium and Org 7684 reduced the endplate current (e.p.c.) amplitude (Ie.p.c.), reduced e.p.c. decay time constant (tau e.p.c.), and increased the e.p.c. train rundown. The effects of vecuronium were not voltage dependent and vecuronium did not change tau noise. The effect of Org 7684 on Ie.p.c. and tau e.p.c. became greater with hyperpolarization, but the effect on e.p.c. train rundown was not voltage-dependent. It is concluded that both vecuronium and Org 7684 produce e.p.c. train rundown and tetanic fade by a prejunctional mechanism. However, whereas postjunctionally vecuronium blocks only the acetylcholine receptor, Org 7684 blocks both the receptor and its associated ion channel. PMID- 2882803 TI - Relaxant effect of the H2-receptor antagonist oxmetidine on guinea-pig and human airways. AB - The effects of three different H2-receptor antagonists (cimetidine, ranitidine and oxmetidine) were tested on isolated preparations of guinea-pig trachea and human bronchus against contractions induced by acetylcholine, histamine and potassium chloride (KCl). In addition, their influence on calcium concentration response curves in guinea-pig tracheal spirals was examined in a potassium-rich solution (30 mM). Finally, their effects were studied in vivo against acetylcholine and histamine-induced bronchoconstriction in anaesthetized guinea pigs. In guinea-pig isolated trachea, oxmetidine--in contrast to cimetidine and ranitidine, which were completely inactive--induced a concentration-dependent relaxation regardless of the excitatory stimulus: its--log EC50 values (i.e. the negative log concentration that caused a 50% relaxation) were 3.46 +/- 0.11, 4.61 +/- 0.09 and 4.20 +/- 0.12 against acetylcholine, histamine and KCl, respectively. In Ca2+-free, K+-enriched solution, the compound was able to inhibit Ca2+-induced contractions at concentrations close to those needed to counteract the spasmogenic effect of histamine in normal Krebs solution. Results obtained in the human bronchus preparation were similar to those observed in guinea-pig tracheal spirals. When tested against acetylcholine or histamine induced bronchoconstriction in vivo, oxmetidine (10 and 30 mg Kg-1 intravenously) significantly reduced the increase in pulmonary airway resistance (Raw) induced by both agents. Once again, cimetidine and ranitidine were completely ineffective. In summary, oxmetidine displayed non-specific antispasmogenic activity on guinea-pig and human airways. This effect, which is independent of H2 receptor blockade, represents a side-effect of the drug which may be connected to its interference with Ca2+ influx and the action or release of intracellular Ca2+. PMID- 2882804 TI - Effects of 5-hydroxy-propafenone in guinea-pig atrial fibres. AB - The effects of 5-hydroxy-propafenone (5-OH-P), an active metabolite of propafenone, were studied on isolated atrial muscle fibres obtained from non treated guinea-pigs and from animals pretreated with 5-OH-P, 3 mg kg-1, for 28 days. In untreated atria 5-OH-P, 10(-8) M-10(-4) M, produced a dose-dependent decrease in amplitude and df/dtmax and reduced the amplitude of the slow contractions induced by isoprenaline and histamine in high K+ media. 5-OH-P also produced a dose-dependent decrease in atrial rate, prolonged the sinus node recovery time and reduced the maximum chronotropic responses to isoprenaline. In untreated atrial muscle fibres 5-OH-P depressed action potential amplitude and Vmax, reduced the resting membrane potential and prolonged the action potential duration (ADP) and the effective refractory period, lengthening the effective refractory period relative to APD. Pretreatment with 5-OH-P reduced atrial rate and increased contractile force, but did not modify the action potential characteristics from the values obtained in untreated atria. Further addition of 5-OH-P produced similar but more marked changes than in untreated atria. It is concluded that in guinea-pig isolated atrial muscle fibres 5-OH-P, like propafenone, exhibits class I (membrane stabilizing), class II (antisympathetic) and class IV (Ca antagonistic) antiarrhythmic actions. Therefore, this metabolite could be responsible, at least in part, for some of the antiarrhythmic effects previously attributed to propafenone. PMID- 2882805 TI - BW A575C, a chemically novel agent with angiotensin converting enzyme inhibitor and beta-adrenoceptor-blocking properties. AB - BW A575C (N-(1-(S)-carboxy-5-[4(3-isopropylamino-2-(R, S)-hydroxypropoxy)indole-2 carboxamido]pentyl)-(R, S)-alanyl-(S)-proline) is a chemically novel agent which exhibits in a single molecule both angiotensin converting enzyme (ACE) inhibition and beta-adrenoceptor-blocking properties. BW A575C produced a competitive blockade of heart rate responses to isoprenaline in a guinea-pig right atrial preparation (pKB 7.18 +/- 0.05, cf. pindolol 8.9 +/- 0.7). BW A575C inhibited a partially purified preparation of ACE obtained from rabbit lung (IC50 10.7 +/- 2.1 nM, cf. enalaprilat, 4.4 +/- 0.8 nM). Intravenous administration of BW A575C (1-100 micrograms kg-1 min-1) to the pithed rat inhibited in a dose-dependent fashion both angiotensin I-induced pressor responses and isoprenaline-induced tachycardia. Dose-ratios obtained from such studies demonstrated that, in this preparation, BW A575C was approximately 100 times more active as an ACE inhibitor than as a beta-adrenoceptor blocking agent. Intravenous administration of BW A575C (1 mg kg-1) to the conscious rat inhibited angiotensin I-induced pressor responses, being approximately equipotent to enalapril and 10 times more potent than captopril. At the same dose, BW A575C had a similar duration of action as an ACE inhibitor to enalapril. Intravenous administration of BW A575C (1 mg kg-1) to either conscious dogs or rats inhibited both angiotensin I-induced pressor responses and isoprenaline-induced heart rate responses. Dose-ratios obtained from such studies demonstrated that in these species, BW A575C was 2-10 times more active as an ACE inhibitor than as a beta-adrenoceptor blocking agent. PMID- 2882807 TI - Neuropathy of the feet due to running on cold surfaces. PMID- 2882806 TI - Treatment of asthma. PMID- 2882808 TI - Macrocytic anaemia in patients treated with sulfasalazine for rheumatoid arthritis. PMID- 2882809 TI - Excitability of 'silent' respiratory neurons during sleep-waking states: an iontophoretic study in undrugged chronic cats. AB - An iontophoretic study of respiratory-related neurons (RN) was conducted in the medullary ventral respiratory area of chronically implanted, undrugged cats during states of sleep and wakefulness. Most RN recorded were unaffected by sleep wake states but a few RN decreased their firing rate during sleep (sleep sensitive cells). The excitability of RN was assessed in the different states by local application of L-glutamate. Glutamate iontophoresis revealed the presence of 5 cells which were silent during sleep and completely or mostly silent during undisturbed wakefulness but always discharged with a respiratory-modulated pattern of the expiratory type in response to glutamate application. Arousing stimuli induced spontaneous firing of these cells and REM sleep reduced glutamate effectiveness. It was concluded that silent RN and RN which become inactive during sleep permanently receive subthreshold respiratory-modulated inputs which are amplified or depressed by state-dependent tonic inputs. PMID- 2882811 TI - Gonadal steroid modulation of neurotransmitter-stimulated cAMP accumulation in the hippocampus of the rat. AB - We have investigated the influences of gonadal and adrenal hormones on neurotransmitter-stimulated cyclic adenosine 3',5'-phosphate (cAMP) formation in hippocampal slices from male and female rats. We found that castration of male rats specifically decreases histamine-stimulated cAMP accumulation, as does administration of estradiol plus progesterone to ovariectomized female rats. In ovariectomized females, activation of cAMP accumulation by isoproterenol was also reduced by estradiol plus progesterone treatment. Although neither of these endocrine manipulations significantly affected stimulation of cAMP accumulation by vasoactive intestinal peptide (VIP), regulation of VIP-stimulated cAMP generation by glucocorticoids was found in female rats. However, the direction of the effect of the synthetic glucocorticoid dexamethasone in females was opposite to its previously demonstrated action in males. These results suggest that gonadal and other steroids may specifically modulate the responsiveness of components of the adenylate cyclase system to certain neurotransmitters, and that such regulation may differ between the sexes and may occur in telencephalic brain regions such as the hippocampus. PMID- 2882810 TI - The alpha 1-noradrenergic antagonist prazosin decreases the concentration of estrogen receptors in female rat hypothalamus. AB - A series of experiments was performed to determine the effects of the alpha 1 noradrenergic antagonist, prazosin, on the concentration of estrogen receptors in female rat brain and pituitary gland. Prazosin caused a dose-dependent decrease in the concentration of cytosol estrogen receptors in mediobasal hypothalamus when injected 10 and 16 h prior to assay. The drug was without effect on the concentration of nuclear estrogen receptors in the absence of estradiol, indicating that the decreased concentration of cytosol estrogen receptors is not due to nuclear estrogen receptor accumulation. Scatchard analysis confirmed that prazosin treatment decreases the concentration of cytosol estrogen receptors without influencing the apparent affinity of the receptors for [3H]estradiol. The prazosin-induced decrease in the concentration of cytosol estrogen receptors in the mediobasal hypothalamus was transient with maximal effects occurring between 8 and 12 h after a single injection. Competition analysis confirmed that prazosin is not an effective competitor for binding to the estrogen receptor in vitro. The effects of prazosin on the estrogen receptor system could not be attributed to modulation of the levels of norepinephrine or dopamine. Assay of the levels of norepinephrine and dopamine in hypothalamus and preoptic area after prazosin injection revealed no effects of prazosin on the level of either of these catecholamines. An estradiol injection resulted in the predicted decrease in the concentration of estrogen receptors accumulating in hypothalamic cell nuclei, suggesting that the cytosol estrogen receptors that decrease in concentration are functional receptors. Prazosin treatment did not result in a decrease in the effectiveness of estradiol in the induction of cytosol progestin receptors in the mediobasal hypothalamus, suggesting that the cells are regulated by the alpha 1 noradrenergic system may not be those cells in which progestin receptors are also induced. These experiments provide further evidence that the noradrenergic system modulates the concentration of estrogen receptors, and perhaps sensitivity to estradiol, in some cells within the rat hypothalamus. PMID- 2882812 TI - Adenosine antagonists increase spontaneous and evoked transmitter release from neuronal cells in culture. AB - To examine the role played by endogenous adenosine in the modulation of transmitter release in the CNS, the effect of adenosine antagonists has been studied. Two systems have been used: EPSPs recorded from pyramidal cells in organotypic hippocampal cultures; and release of newly synthesized [3H]glutamate from cerebellar granule cells in dissociated culture. Bath application of 0.1-1 microM 8-phenyltheophylline (8-PT) reversibly increased both the number and size of spontaneous EPSPs and caused bursting activity in some cells. This effect was blocked by the glutamate antagonist gamma-D-glutamylglycine (DGG) (1 mM) but not by atropine (10 microM) or bicuculline (100 microM). Another adenosine antagonist isobutylmethylxanthine (IBMX, 10 microM) had a similar effect to 8-PT. Spontaneous activity in pyramidal cells and that induced by adenosine antagonists was blocked by the adenosine agonist 2-chloroadenosine (2-CA) (0.2-20 microM). 8 PT (10 microM) markedly potentiated K+-stimulated release of newly synthesized glutamate, and also enhanced basal glutamate release. The agonist (-) phenylisopropyladenosine ((-)-PIA, 2 microM) which is relatively selective for A1 receptors, reduced by 19 +/- 5% the 8-PT-induced enhancement, and reduced K+ stimulated glutamate release in the absence of 8-PT to a similar extent. In contrast 5'-N-ethylcarboxamido adenosine (NECA, 2 microM), which is a relatively selective A2 agonist, slightly enhanced glutamate release. From these results it is likely that 8-PT potentiates glutamate release in both systems by blocking the effect of endogenous adenosine on presynaptic A1 receptors. PMID- 2882813 TI - Dissociation of antinociceptive from cardiovascular effects of stimulation in the lateral reticular nucleus in the rat. AB - The lateral reticular nucleus (LRN) in the caudal ventrolateral medulla has been implicated in the regulation of spinal nociceptive transmission and hemodynamics. Experiments were undertaken to examine the relationship between inhibition of the tail flick reflex and cardiovascular effects produced by electrical stimulation in the LRN in rats lightly anesthetized with pentobarbital. Intensity- and frequency-dependent increases in mean arterial pressure and vascular resistance in the hindquarter, mesenteric, renal and caudal arterial beds were observed. Inhibition of the tail flick reflex, however, occurred at intensities of electrical stimulation which produced no significant changes in mean arterial pressure or vascular resistance in any of the arterial beds studied. Selective stimulation of cell bodies in the LRN by microinjection of glutamate similarly inhibited the tail flick reflex but produced significant reductions in mean arterial pressure, without substantially affecting regional vascular resistances. These results suggest that the antinociceptive and depressor effects of stimulation in the LRN are mediated by activation of cell bodies, while pressor effects produced by focal electrical stimulation are mediated by activation of fibers of passage. The descending inhibition produced by stimulation in the LRN is independent of stimulation-produced cardiovascular responses. PMID- 2882814 TI - Studies on the effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in C57BL/6 mice. Comparison with three other strains of mice. AB - The effect of the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) on central catecholamine neurons in C57BL/6 mice has been studied employing neuro- and histochemical techniques. The number of dopamine (DA) cell bodies in substantia nigra pars compacta (SNC) was reduced by 70% in MPTP-treated C57BL/6 mice, as demonstrated both by tyrosine hydroxylase (TH) immunohistochemistry and conventional histology (Cresyl violet staining) and an almost complete loss of DA fibers in striatum was also found. A detailed analysis of the effects of MPTP on endogenous catecholamine levels in various brain regions revealed that MPTP caused a severe reduction of endogenous DA in substantia nigra and striatum (35 and 5% of control) which was accompanied by an increase in the 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio. There was also a decrease of DA in nucleus accumbens and the olfactory tubercle to 41 and 44% of control, respectively, without any significant change in the DOPAC/DA ratio and density of TH-positive fibers. Small but significant decreases of the noradrenaline (NA) levels in septum, entorhinal cortex and frontal cortex were seen, although the uptake of [3H]NA in frontal cortex was not significantly changed. Minor MPTP-induced decreases of the serotonin levels in frontal cortex, occipital cortex and spinal cord were also seen. The MPTP treatment also induced a 55% increase of adrenaline levels in hypothalamus, while no changes were seen in pons-medulla and spinal cord. Comparing this with 3 other strains of mice, the MPTP-induced reduction of endogenous DA in striatum was most pronounced in C57BL/6, less in N.M.R.I. and CBA/Ca mice, and least in Swiss-Webster. Concerning the effect of MPTP on cortical NA levels, the same relation was at hand except for C57BL/6, where, as mentioned, the effect was merely detectable. No reduction of DA perikarya in SNC was seen in Swiss-Webster mice. These findings show that in mice major differences exist in sensitivity of catecholamine neurons to MPTP between different strains. The data show that MPTP can produce an almost complete, permanent and relatively selective degeneration of the nigrostriatal DA neurons in C57BL/6 mice similar to that seen in primates. This strain may therefore serve as a useful model for studies on various aspects of MPTP-induced parkinsonism. PMID- 2882815 TI - Intranigral dynorphin-1-13 suppresses kindled seizures by a naloxone-insensitive mechanism. AB - Numerous lines of evidence indicate that the substantia nigra (SN) facilitates the propagation of seizures in kindling and in other seizure models. Intranigral injection of dynorphin-1-13 exerted a potent seizure suppressant action in kindled rats. This seizure suppressant action was dose dependent, spatially specific for the area of the SN and was not blocked by naloxone (2 mg/kg i.p.). This finding extends previous work indicating that treatments which reduce SN output exert an anticonvulsant action and further suggests that opioid peptides endogenous to the SN may regulate seizure susceptibility in the kindling model. PMID- 2882816 TI - Evidence for epinephrine-induced depolarization in neurons of bullfrog sympathetic ganglia. AB - The response to epinephrine (EP) was determined for neurons in bullfrog sympathetic ganglia by intracellular and voltage-clamp recording techniques. EP (5 microM-1 mM) produced a concentration-dependent depolarization mediated through beta-adrenoceptors. The EP-induced depolarization (EPD) was associated with a decrease in the membrane conductance. The EP-induced current (EP1) was decreased at hyperpolarizing potential levels and nullified at -70 mV. No reversal of the EPI polarity was seen. It is concluded that the EPD is generated by the suppression of a voltage-dependent gK, probably the M-channel. PMID- 2882817 TI - Regional levels of neurotransmitter-related markers in the brain of the weakly electric fish Gnathonemus petersii. AB - The regional distribution of neurochemical markers for cholinergic, GABAergic and glutamatergic/aspartatergic transmission has been studied in several brain areas of the weakly electric fish Gnathonemus petersii. In particular, brain regions related to reception, relaying and processing of electrosensory modalities have been examined. The regional distribution of neurotransmitter-related markers is considered in the light of available anatomical data and is discussed with particular emphasis on differences among different parts of the hypertrophic valvula cerebelli and other cerebellar structures. PMID- 2882818 TI - Dopaminergic axons directly make synapses with GABAergic neurons in the rat neostriatum. AB - We examined with an electron microscopic 'mirror technique' whether glutamic acid decarboxylase-immunoreactive (GAD-IR) neurons are in direct synaptic contact with tyrosine hydroxylase-immunoreactive (TH-IR) axons in the rat neostriatum. Three types of GAD-IR neurons were identified in the nucleus caudatus putamen based upon their size and ultrastructural characteristics. These were medium spiny, medium aspiny and large cells. All types of GAD-IR neurons made synaptic contact with TH-IR axonal boutons at least on perikarya and proximal dendrites. This provides ultrastructural evidence for catecholaminergic, presumably, nigrostriatal dopaminergic inputs to both long- and short-axon neurons most probably containing GABA. PMID- 2882819 TI - Enhancement of [3H]glutamate binding by N-methyl-D-aspartic acid in rat adrenal. AB - Some neurochemical characteristics of [3H]L-glutamic acid binding sites were studied using membranous homogenate preparations obtained from the rat adrenal. It was found that the binding was inhibited by the addition (10(-7)-10(-3) M) of L-isomers of structure-related compounds in a concentration-dependent manner. A significant inhibition of the binding was induced by L-glutamic acid diethylester, but not by alpha-aminoadipic acid. Scatchard analysis revealed that the binding sites consisted of a single component with a Kd of 0.19 +/- 0.05 microM and a Bmax of 4.11 +/- 0.71 pmol/mg protein, respectively. In vitro addition of sodium acetate (1-100 mM) elicited a stimulatory action on the binding at 2 degrees C, while inducing a significant attenuation of the binding at 30 degrees C. The binding reached a plateau within 30 min of incubation followed by a gradual decline up to 60 min in the presence of 100 mM sodium acetate at 30 degrees C, whereas the binding continued to increase up to 60 min in the absence of sodium acetate. Addition (0.1-10 mM) of N-methyl-D-aspartic acid (NMDA), one of the agonists for central excitatory amino acid neurotransmitter receptors, exerted a significant augmentation of the adrenal binding independently of the incubation temperature in a concentration-dependent manner. The latter facilitation of the binding, however, was not affected by the classical antagonists for central NMDA receptors such as 2-amino-5 phosphonovaleric acid and 2-amino-7-phosphonoheptanoic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882820 TI - Distinct topographical localisation of two somatostatin receptor subpopulations in the human cortex. AB - The use of two different radioligands, [125I]Leu8, D-Tryp22,Tyr25-somatostatin-28 and the stable somatostatin octapeptide analog [125I]204-090, D-Phe-Cys[125I]Tyr D-Trp-Lys-Thr-Cys-Thr(ol), allowed to differentiate between two somatostatin receptor subpopulations in the human cortex. In homogenates, octapeptide somatostatin analogs displaced only part of the somatostatin-28 radioligand with high affinity. Autoradiography showed that the receptor subpopulation labelled with [125I]204-090, which we named SS1, was preferentially localized in layers V and VI, whereas the subpopulation having low affinity for somatostatin octapeptides (named SS2), measured with somatostatin-28 radioligand, was concentrated in the superficial cortical layers (I-IV) and particularly enriched in parts of lamina IV. PMID- 2882821 TI - Cellular localization of N-acetylaspartylglutamate in amphibian retina and spinal sensory ganglia. AB - Antisera were produced against N-acetylaspartylglutamate (NAAG) and were used to localize the molecule within the retina and spinal sensory ganglia of Rana pipiens. NAAG immunoreactivity (IR) in the retina was confined to a subpopulation of amacrine and bipolar cells. The dipeptide was present in the perikarya of these cells and their neurites which terminated in two discrete bands of the inner plexiform layer. Some NAAG-IR was also present in the outer plexiform layer and the inner segment layer. In spinal ganglia, a subpopulation of relatively large sensory neuron cell bodies expressed NAAG-IR. These data are consistent with the hypothesis that this dipeptide has a function which is specific to discrete subclasses of neurons. In the amphibian retina, the NAAG distribution can be related to the reported involvement of the N-methyl-D-aspartate receptor in neurotransmission at the level of amacrine and ganglion cells. PMID- 2882822 TI - Involvement of alpha-adrenergic and GABAergic mechanisms in growth hormone secretion induced by central somatostatin in rats. AB - Brain opiatergic, alpha-adrenergic and GABAergic mechanisms are known to play a stimulating role in growth hormone (GH) secretion in the rat. Plasma GH levels were increased by intracerebroventricular (i.c.v.) injection of somatostatin-14 (SRIF-14, 5 micrograms/rat) in conscious rats. GH release induced by i.c.v. SRIF 14 was blunted by either intravenous (i.v.) injection of phenoxybenzamine (500 micrograms/100 g b. wt.), an alpha-adrenergic blocker, or picrotoxin (150 micrograms/100 g b. wt.), a GABA antagonist, in the rat. On the other hand, i.v. injection of naloxone (125 micrograms/100 g b. wt.), an opiate antagonist, did not affect GH release induced by i.c.v. SRIF-14. These findings suggest that alpha-adrenergic and GABAergic mechanisms but not opiatergic mechanisms are involved in central SRIF-induced GH secretion in the rat. PMID- 2882823 TI - Non-uniform release at the frog neuromuscular junction: evidence of morphological and physiological plasticity. AB - The frog neuromuscular junction (NMJ) is a fusiform structure parallel to the muscle fiber with a few secondary and tertiary branches. Both sprouting and regression can occur on the same nerve terminal, suggesting a continuous on-going remodelling of the mature neuromuscular junction. Thus, the frog NMJ is a dynamic structure. Ultrastructural observations of the nerve terminal suggest that the active zones are distributed equally along the mature nerve terminal. Disorganized active zones have however been observed in distal regions. The density of synaptic vesicles is also uniform throughout the whole structure. However, mitochondria appear to be more abundant in the very distal regions of the nerve terminal. The postjunctional folds and the cholinergic receptors are also uniformly distributed along the NMJ. However, during remodelling periods, the distributions of postjunctional folds and of cholinergic receptors are not uniform in the degenerating and regenerating regions. Fig. 1 summarizes these morphological data. The frequency of spontaneous release (MEPPs) at the NMJ is higher in the proximal region than in the distal regions and recent evidence suggests that the mean MEPP amplitude is higher in the proximal than in the distal portions. Evoked transmitter release is also non-uniform along the frog NMJ. As for spontaneous release, it is higher in the proximal regions than in the distal regions. Failures of the active propagation of the PNAP at low safety points, such as the end of the myelinated axon and the branching points, may be one of the mechanisms responsible for unequal evoked release. It is also possible that the PNAP does not actively invade the whole extend of the nerve terminal since Na+ channels are absent from the distal regions. Fig. 2 summarizes these physiological data. PMID- 2882825 TI - Tyrosine hydroxylase immunochemistry and quantitative light microscopic studies of the mesolimbic dopamine system in rat brain: effects of chronic methamphetamine administration. AB - Long-term treatment of rats with methamphetamine (20 mg/kg, IP, every 12 hours for 10 days) resulted in a large decrease in tyrosine hydroxylase staining axons and terminal boutons in the nucleus accumbens and frontal cortex, as well as the ventral tegmental area of the midbrain, when examined 60 days following termination of the drug treatment regimen. Quantitative analysis showed a 71 and 78% decrease in tyrosine hydroxylase staining processes in the nucleus accumbens and frontal cortex, respectively, and a 90% decrease in tyrosine hydroxylase positive material in the ventral tegmental area. Thus, tyrosine hydroxylase enzyme in both the cell bodies of the midbrain ventral tegmental area as well as in the nerve terminals in post-synaptic target regions of the forebrain is depleted by chronic methamphetamine administration. PMID- 2882824 TI - Diurnal rhythms in the responsiveness of hippocampal pyramidal neurons to serotonin, norepinephrine, gamma-aminobutyric acid and acetylcholine. AB - Radioligand binding studies have revealed the existence of endogenous circadian rhythms in the number of several receptors in the rat brain. The present microiontophoretic study was undertaken to assess diurnal rhythms in the responsiveness of rat hippocampal pyramidal neurons to serotonin (5-HT), norepinephrine (NE), gamma-aminobutyric acid (GABA), and acetylcholine (ACh). Between December and April, there was a significant diurnal variation in the responsiveness of hippocampal pyramidal neurons to 5-HT and ACh. Between May and August, the responsiveness to NE and ACh showed a diurnal variation. There was no diurnal variation in the responsiveness to GABA in either period of the year. Short-term exposure to constant light or darkness produced a phase-shift of the serotoninergic and cholinergic rhythms, suggesting their endogenous nature and their synchronization to clock-time by the light-dark cycle. The diurnal rhythms in responsiveness to 5-HT and NE underwent phase-shifts from the December-April to the May-August period in rats entrained to 12:12 light-dark cycle, suggesting the existence of seasonal modulation of these rhythms. These circadian rhythms in the postsynaptic responsiveness of hippocampal pyramidal cells and their seasonal fluctuation may be related to the diurnal variation of mood seen in major depression as well as to the seasonal incidence of this illness. PMID- 2882826 TI - Latency of transmitter release at crayfish motor nerve endings examined by intracellular depolarization. AB - Latency of release of individual quanta of transmitter was studied at neuromuscular junctions of a crayfish (Procambarus clarkii). Postsynaptic quantal currents were recorded at individual motor nerve endings with a macropatch electrode while the subterminal axon branch was depolarized by current passed through an intracellular microelectrode. For depolarizing currents of moderate size, the latency of transmitter release did not change when the duration of the depolarizing current was altered. Previous studies in which a contrary result was obtained may have been compromised by artefacts or by the sampling methods employed. The present results do not support the hypothesis of a depolarization induced "repressor" of quantal release. PMID- 2882827 TI - Interactions of some partial agonists with high and low affinity binding sites in beta-adrenoceptors. AB - Interactions of derivatives of befunolol (BFE-37, BFE-55, and BFE-61), carteolol, and pindolol with beta-adrenoceptors were tested in guinea pig isolated taenia caecum. All the drugs used acted as partial agonists on the beta-adrenoceptors when compared with isoprenaline, a full agonist. The pA2 values of BFE-61, carteolol, and pindolol were significantly larger than their pD2 values, while there was no significant difference between the pA2 and pD2 values for BFE-37 and BFE-55. The specific binding of [3H]befunolol to microsomal fractions from the guinea pig taenia caecum distinguished two binding sites, high affinity and low affinity sites. Both sites are considered to be bound by 50 nM of [3H]befunolol. Specific 3H binding was displaced by BFE-61, carteolol, and pindolol in a biphasic manner but in a monophasic manner by BFE-37 and BFE-55. Furthermore, [3H]befunolol binding was only partially displaced by BFE-55 but completely displaced by the other drugs used. These results, together with our previous findings, suggest that BFE-61, carteolol, and pindolol discriminate between the two affinity binding sites in the beta-adrenoceptors, which are not discriminated between by BFE-37, and further that BFE-55 may bind with only the high affinity site. PMID- 2882829 TI - Inotropic responses of the left ventricle to changes in heart rate in anesthetized rabbits. AB - Factors known to influence left ventricular contractility include preload, afterload, circulating catecholamine concentration, efferent sympathetic discharge, and heart rate. Heart rate influences have been primarily determined in the dog, whereas the influence of heart rate in smaller mammals has not been determined. Eight pentobarbital-anesthetized rabbits were instrumented to measure electrocardiogram, heart rate, left ventricular pressure, end-diastolic pressure, dP/dt, and mean and pulsatile aortic pressures. Systematic bradycardia was induced by stimulating the peripheral end of the sectioned right vagus nerve. Between 293 and 235 beats/min, there was no change in (dP/dt)max as heart rate was decreased. Below this range there was a direct relationship between (dP/dt)max and heart rate. Preload remained unchanged down to 132 beats/min. There was a small but significant decrease in afterload (0.09 mmHg X beat-1 X min 1; 1 mmHg = 133.32 Pa) throughout the decrease in heart rate. Infusion of propranolol (2.0 mg/kg) produced no marked change in the heart rate - (dP/dt)max relationship, although both resting heart rate and (dP/dt)max were reduced. This study demonstrates that (dP/dt)max is not influenced by changes in heart rate above 235 beats/min in the pentobarbital-anesthetized rabbit. These results differ from findings in other animals, and demonstrate that species and heart rate ranges must be considered when drawing conclusions regarding (dP/dt)max as a reliable index of contractility. PMID- 2882828 TI - Substrate supply for thermogenesis induced by the beta-adrenoceptor agonist BRL 26830A. AB - The nature of the substrate that fuels the thermogenic response to the novel beta adrenoceptor agonist BRL 26830A has been investigated. Respiratory quotient measurements indicated that the increase in metabolic rate produced by BRL 26830A in rats was fuelled wholly by lipid. BRL 26830A also produced a marked reduction in the lipid content of total dissectable brown adipose tissue. The energy content of this lipid lost during the 4-h period after dosing was equivalent to approximately 50% of the thermogenic effect of the compound over the same period, suggesting that lipid stored in brown adipose tissue is a major initial fuel for BRL 26830A induced thermogenesis. However, marked depletion of brown adipose tissue lipid prior to administration of BRL 26830A had no effect on the subsequent thermogenic response to the compound. Oral administration of glucose altered the pattern of fuel utilization for resting metabolism, but thermogenesis was still fuelled mainly by lipid. Administration of methyl palmoxirate, which inhibits oxidation of long-chain fatty acids, completely prevented the thermic effect of BRL 26830A, suggesting that lipid is a necessary fuel for this process. These results do not support suggestions that carbohydrate is quantitatively important as a fuel for nonshivering thermogenesis. PMID- 2882830 TI - Antagonistic effect exerted by three strictly anaerobic strains against various strains of Clostridium perfringens in gnotobiotic rodent intestines. AB - Our purpose was to study bacterial antagonism between a limited number of strictly anaerobic strains and Clostridium perfringens in the intestinal tract of gnotobiotic rodents. Gnotobiotic mice harboring a Bacteroides thetaiotaomicron, a Fusobacterium necrogenes, and a Clostridium sp. strain were protected against pathogenic B, C, and D C. perfringens serotypes. A drastic antagonistic effect of this three-strain association was also observed against a nonpathogenic C. perfringens serotype A (CpA). It was less efficient in gnotobiotic rats than in mice and less efficient in gnotobiotic mice fed an autoclaved diet than in mice fed the same diet sterilized by irradiation. No diffusible inhibitory substances against CpA were detected in feces of gnotobiotic mice harboring the three antagonistic strains, and no nutrient depletion was demonstrated in filtrates prepared from 10-fold diluted feces of these mice. In vitro mixed cultures of the three antagonistic strains failed to inhibit growth of CpA, whereas CpA did not multiply in a 10-fold diluted feces from gnotobiotic mice. A reverse correlation between the initial number of antagonistic strains and the division number of CpA was determined using serially diluted fecal suspensions. Thus, large numbers of viable cells of both antagonistic strains were required to inhibit the target strain in fecal suspensions as was also found in gnotobiotic mice intestines. However, no diffusible inhibitory substance was detectable nor could depletion of growth factors be identified as causing antagonism. Whatever factors that may be responsible for antagonism were found to be influenced by the host and its diet. PMID- 2882831 TI - Electron microscopic description of glycocalyx and fimbriae on the surface of Pasteurella haemolytica-A1. AB - Several electron microscopic techniques were used to examine the surface of cells of Pasteurella haemolytica (biotype A, serotype 1) grown in vitro. All methods showed the presence of a very extensive glycocalyx on logarithmic phase (6 h) cells grown in liquid media. The anionic glycocalyx of these cells stained well with ruthenium red, but collapsed during dehydration for electron microscopy unless stabilized with specific antibodies. When the same techniques were used to examine cells in the stationary phase (18 h) the glycocalyx was much reduced. Large numbers of fimbriae were seen on both 6 h and 18 h cells grown in fluid media without shaking. In summary, logarithmic phase cells of P. haemolytica have both fimbriae and extensive anionic glycocalyx at their surface and we suggest that either or both of these structures may be important in the colonization of the bovine respiratory tract and the subsequent pathogenesis of Pasteurella pneumonia. PMID- 2882833 TI - PRN medication for psychiatric inpatients. AB - Little is known about the extent of the use of prn psychotropic medication in psychiatric inpatient units. A survey of the prn prescription and administration of psychotropic drugs in a psychiatric teaching hospital revealed that a large number of inpatients were prescribed and administered such drugs on a prn basis. Although 50% of the prescriptions were never administered, only 25% were actively discontinued by physicians. A diagnosis of personality disorder was the factor most frequently associated with the rate of prn prescriptions and of administrations. A large number of prn prescriptions had no instructions for indications, minimum time spacing between doses or maximum daily dosage. It is suggested that hospitals monitor the prn use of psychotropic medications in their inpatient units, and explore the reasons for such use. Psychotropic drug use on a prn basis should preferably be reserved for emergencies, and the instructions of prn prescriptions should be clear and detailed. PMID- 2882832 TI - Beta-blocker therapy and the risk of anaphylaxis. AB - Beta-blocker therapy is associated with an increase in the severity and, possibly, the incidence of acute anaphylaxis. The population at risk consists of people with allergic conditions who are given a beta-blocker for an unrelated condition. Anaphylaxis under these conditions may be severe, protracted and resistant to conventional treatment because of the beta-adrenergic blockade. Severe or fatal attacks have been triggered by insect stings, the ingestion of allergenic foods or drugs, and injections of radiocontrast media, antisera or immunotherapy antigens. These occurrences are probably infrequent, but their incidence is unknown. At least two fatal cases have recently occurred in Canada. Clinical allergists, internists and family practitioners in particular should be aware of the need for aggressive and prolonged support in patients who experience anaphylaxis while receiving beta-blocker therapy and should report all such occurrences to the federal registry of adverse drug reactions. Allergy skin testing or immunotherapy is inadvisable in patients who take a beta-blocker orally or in the form of ophthalmic eyedrops. The list of relative contraindications to beta-blocker use should be extended to include susceptibility to recurrent anaphylaxis, whether it is idiopathic or due to an identifiable cause. PMID- 2882834 TI - Glutathione and related enzymes in rat brain tumor cell resistance to 1,3-bis(2 chloroethyl)-1-nitrosourea and nitrogen mustard. AB - Reduced glutathione (GSH) and activities of several glutathione-related enzymes were measured in two 9L rat brain tumor cell lines with differing sensitivities to both 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and nitrogen mustard. GSH, measured by a specific high-performance liquid chromatographic method, was found to be approximately twice as high in 9L cells sensitive to BCNU but resistant to nitrogen mustard. The nitrogen mustard resistant cell line was also found to have 2.5-fold more bulk glutathione transferase activity and approximately 3-fold more gamma-glutamyl transpeptidase activity. Glutathione reductase activity, protein thiol, and total protein content were similar in the two cell lines. Pretreatment of 9L cells with 50 microM buthionine sulfoximine for 24 h to deplete GSH only slightly potentiated BCNU cytotoxicity in a clonogenic assay whereas that of nitrogen mustard was markedly potentiated in both cell lines. Similarly, buthionine sulfoximine pretreatment had little effect on the induction of sister chromatid exchanges by BCNU, but significantly increased the number of sister chromatid exchanges induced by nitrogen mustard in both cell lines. Depleting GSH also had no significant effect on the cytotoxicity of 1-(2-chloroethyl)-3 cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1 nitrosourea to 9L cells. Pretreatment of 9L cells with 1 mM GSH significantly protected against nitrogen mustard cytotoxicity. Moreover, nitrogen mustard incubated with GSH and glutathione transferase was 4-fold less cytotoxic than nitrogen mustard incubated with GSH alone. Incubation of BCNU with GSH alone or with glutathione transferase had no effect on BCNU cytotoxicity. These results indicate that elevated GSH and glutathione transferase activity is one mechanism of cellular resistance to nitrogen mustard in the 9L cell line, but it does not correlate with resistance to BCNU or other clinically important nitrosoureas. PMID- 2882835 TI - Effect of recombinant human tumor necrosis factor on the induction of murine macrophage tumoricidal activity. AB - The ability of recombinant human tumor necrosis factor (rH-TNF) alone or in combination with lymphokines (LK) to induce the in vitro activation of murine macrophages was evaluated. The treatment of C57BL/6 mouse resident peritoneal exudate cells (PEC) with rH-TNF and LK was found to induce the activation of macrophages to a tumoricidal state against P815 mastocytoma cells. Neither rH-TNF nor LK alone induced macrophage cytotoxic activity. Furthermore, the macrophage activation seen was not due to small amounts of contaminating lipopolysaccharide. The TNF plus LK-mediated macrophage activation could be totally ablated by rabbit antiserum to murine gamma-interferon, thus suggesting a role for gamma-interferon in this system. Since adherent cells (greater than or equal to 95% macrophages) only marginally responded to stimulation with rH-TNF plus LK and the addition of nonadherent PEC caused a marked augmentation of rH-TNF plus LK-mediated macrophage activation, the involvement of nonadherent PEC was suggested. In addition, using antibodies and complement to deplete subsets of cells from the nonadherent PEC, the requirement for cells bearing Thy 1.2 and asialo GM1 surface markers was demonstrated. These results suggest that TNF may play an autocrine regulatory role in concert with lymphokines in macrophage-mediated host defense against malignant neoplasia. PMID- 2882836 TI - Continued development of hepatic gamma-glutamyltranspeptidase-positive foci upon withdrawal of 17 alpha-ethynylestradiol in diethylnitrosamine-initiated rats. AB - Adult ovariectomized Sprague-Dawley rats were administered a single initiating dose of 200 mg diethylnitrosamine (DEN)/kg, i.p. 17 alpha-ethynylestradiol (EE2) was then chronically administered to the rats by means of s.c. Silastic implants at an estimated dose of 90 micrograms EE2/kg/day. Hepatic gamma glutamyltranspeptidase-positive foci were evaluated after 20-60 (+20,+30,...,+60) weeks of chronic EE2 treatment and after 20 or 30 weeks of EE2 followed by 20 or 30 weeks with no EE2 [(+20,-20), (+30,-20), (+30,-30)] to determine the effects of withdrawal of the promoting agent on the persistence or reversibility of these focal lesions. Our results show that gamma-glutamyltranspeptidase-positive foci are no longer dependent on exogenous EE2 administration for their continued growth in initiated animals given EE2 chronically for 20 weeks. In DEN-initiated, EE2-promoted animals the number of foci per cc (Nv) seen at 20 weeks increased over the next 20 weeks in the absence of further EE2 treatment, but was not statistically different than Nv for continued EE2 treatment. The proportion of total liver volume occupied by foci (Vv) was 0.0054 (+30), 0.0191 (+30,-20), and 0.0135 (+50). The (+30,-20) Vv was significantly different than that for (+30) (P less than 0.01). Hepatocellular adenomas and carcinomas were detected in DEN initiated and EE2- promoted animals as early as 30 weeks. Hepatic tumor incidence continued to increase after withdrawal of EE2 in initiated animals which had received only 30 weeks of promotion. Within the framework of our studies, the promoting effects of EE2 do not appear to be reversible by withdrawal of EE2 after 20 weeks of treatment. It may be that events or factors which were estrogen dependent in the early stages of promotion are now constitutive. PMID- 2882837 TI - Phase I clinical and pharmacokinetic study of taxol. AB - Taxol, selected for clinical trial because of its animal antitumor activity and unique structure and mechanism of action, was administered in Cremophor by i.v. infusion over 6 h in a phase I study. Eastern Cooperative Oncology Group toxicity grading was used. Eighty-three taxol courses were administered to 34 patients. Grade 3-4 hypersensitivity reactions occurred in 4 of 13 courses at the first 2 dose levels, but premedication with dexamethasone, diphenhydramine, and cimetidine resulted in only 3 additional Grade 2 reactions in the next 70 courses. Neurotoxicity, which resolved or improved after stopping therapy, was Grade 1 with 2 of 10 courses of 230 mg/m2 and Grades 1-3 after 11 of 12 courses of 275 mg/m2. Leukopenia, first seen (Grade 1) after 1 of 8 75 mg/m2 courses, was Grades 3-4 after 10 of 34 courses of 175-230 mg/m2 and 10 of 12 courses of 275 mg/m2. The WBC nadir occurred at a median of 10 days and the median time required for normalization of the WBC was 18 days. Alopecia began 2-3 weeks posttaxol in 2 of 9 patients treated with 75-135 mg/m2 and in all 16 patients (Grade 3) treated with 175-275 mg/m2. Grades 1-2 nausea and vomiting occurred in about one-third of the patients treated at a dose of 105 mg/m2 or more. Taxol disappearance from plasma was biphasic; half-lives of the first and second phases after a 275 mg/m2 dose were 0.32 and 8.6 h, respectively. The apparent volume of distribution was 55 liters/m2, and the peak plasma concentration with a dose of 275 mg/m2, which occurred immediately postinfusion, was approximately 8 microM. Only 5% of parent drug was excreted in the urine within 24 h. Minor objective responses were noted in one patient with gastric cancer and another with ovarian carcinoma. In addition, one patient with massive ascites due to metastatic adenocarcinoma from an unknown primary had only minimal sonographic evidence of ascites for 6 months posttreatment. Neurotoxicity and leukopenia were dose limiting in this schedule. The recommended phase II trial dose is 250 mg/m2, with premedication. PMID- 2882838 TI - Biochemical characteristics of D1 dopamine receptors: relationship to behavior and schizophrenia. PMID- 2882840 TI - Plasma neuroleptic concentration: in search of a therapeutic window. PMID- 2882839 TI - Current views on endogenous ligands for opiate recognition sites. PMID- 2882841 TI - Advantages and disadvantages of depot-neuroleptics as maintenance medication for chronic schizophrenics. PMID- 2882842 TI - Memory: peptide, neurotransmitters and drug influences. PMID- 2882843 TI - Clozapine: neuroendocrine studies of an atypical neuroleptic. PMID- 2882844 TI - Pharmacological and biochemical properties of iminodibenzyl antipsychotic drugs including Y-516 and clocapramine. PMID- 2882846 TI - Beta-adrenoceptor blocking drugs in the treatment of morbid anxiety. PMID- 2882845 TI - Classification of neuroleptics based on their pharmacokinetics. PMID- 2882847 TI - Beta-blockers and acute situational stress. PMID- 2882848 TI - Evaluation of optimal doses of a neuroleptic: preliminary results. PMID- 2882849 TI - Detection of 3-deoxy-2-octulosonic acid in thiobarbiturate-negative endotoxins. PMID- 2882851 TI - [The significance of neuropeptides in the theory of digestive system regulation]. PMID- 2882852 TI - [Regulatory peptides of the digestive system. Development of findings and new aspects]. PMID- 2882853 TI - Variations in crypt cell cycle time. PMID- 2882850 TI - Mechanism of leukemogenesis by human T-cell leukemia virus types I and II: role of the lor gene. AB - The human T-cell leukemia (HTLV) family of viruses now include two groups of transforming viruses (HTLV-I and HTLV-II) and one group of viruses with immunosuppressive activity but no apparent transforming ability (HTLV-III). Nucleotide sequence analysis of an HTLV-I provirus by Seiki et al [Proc Natl Acad Sci USA 1982: 6899-902] has revealed a distinct region of the genome located between env and the long terminal repeat sequences (LTR). Analysis of a variant of HTLV-I, called HTLV-Ib, which retains transforming ability, revealed a deletion in the 5' portion of this sequence that indicates that this portion of the sequence probably does not play an essential role in transformation. Hybridizations at varying stringencies show that at least a portion of this additional region of HTLV-I and -II is more highly conserved than most other regions of the genome. The DNA sequence of this HTLV-II region localizes the area of homology within the 1,000 base pairs just upstream of the LTR; the remainder of the region is not conserved. The conserved region includes a long open reading frame, is denoted lor, and has the coding capacity for a protein of at least 38 kilodaltons (kd). Studies of the transcriptional activity of the LTR sequences show that the rate of LTR-directed transcription is greatly augmented in HTLV infected cells, a phenomenon called trans-acting transcriptional regulation. It is suggested that transformation of lymphocytes by HTLV-I or -II is mediated by action of HTLV-encoded trans-acting transcription factors on cellular genes that control the replication of lymphocytes. PMID- 2882855 TI - The role of tubulin polymerization during spindle elongation in vitro. AB - We describe the effect of exogenous tubulin on reactivation of anaphase spindle elongation in isolated diatom spindles. In the absence of tubulin, spindle elongation is limited to the equivalent of the microtubule overlap zone, but in the presence of tubulin spindle elongation is several times the length of the overlap zone. Biotinylated neurotubulin is incorporated into the overlap zone and around the poles. Before spindles have elongated by the equivalent of the overlap zone, there are two regions of incorporated tubulin flanking this zone. After further elongation, there is one broad zone of incorporated tubulin in the spindle midzone. Spindle elongation and the pattern of tubulin incorporation into the midzone, but not the poles, are ATP-dependent and vanadate-sensitive. These results suggest that tubulin adds onto the ends of microtubules in the overlap zone, which then slide through the midzone as the spindle elongates. PMID- 2882854 TI - Insulin-, glucagon- and somatostatin-like immunoreactivity in the endocrine pancreas of the lungfish, Neoceratodus forsteri. AB - The endocrine pancreas of the Australian lungfish, Neoceratodus forsteri, was investigated immunocytochemically for the presence of polypeptide hormone producing cells. Three cell types were identified, namely insulin-, glucagon-, and somatostatin-immunoreactive elements. The insulin cells are confined solely to the center of the islets. Glucagon and somatostatin cells are distributed peripherally around the central mass of the insulin cells. Isolated cells or clusters of glucagon and somatostatin cells are also dispersed within the exocrine parenchyma. The immunoreactive cell types are compared with those staining with standard histological procedures. The spatial relationships of the different cell populations are examined. PMID- 2882856 TI - Biogenesis of E. coli Pap pili: papH, a minor pilin subunit involved in cell anchoring and length modulation. AB - The biogenesis of Escherichia coli Pap pili, encoded by the pap gene cluster, was studied. A novel gene, papH, was identified and found to encode a weakly expressed pilin-like protein. PapH was dispensable for digalactoside-specific binding and for formation of Pap pili. However, in papH deletion mutants 50%-70% of total pilus antigen was found free of the cells. We present evidence showing coregulation of papH and the adjacent gene, papA, which encodes the major pilin subunit. A decrease in the PapA to PapH ratio resulted in a large fraction of cells producing shortened pili, whereas overproduction of PapA relative to PapH resulted in cells with lengthened pili. The data show that PapH has roles in anchoring the pilus to the cell and in modulating pilus length. PMID- 2882857 TI - Molecular characterization and expression of sevenless, a gene involved in neuronal pattern formation in the Drosophila eye. AB - The Drosophila sevenless mutation results in lack of a single neuron (photoreceptor cell R7) in every ommatidium of the compound eye; the developmental defect occurs in the larval eye disc. We created P-element-induced alleles and used them to isolate the sev gene. An 8.2 kb transcript is expressed in the eye disc, behind the morphogenetic furrow, coincident with recruitment and differentiation of photoreceptor clusters. The transcript becomes localized at the apical surface, persists in the prepupa, and fades out at pupation. It is again detected in the adult head. In some alleles the 8.2 kb transcript is absent. In others, the transcript is expressed, in spite of the absence of cell R7. Localization of the gene product in the eye disc was obtained with antibody raised against sev protein. PMID- 2882858 TI - Promoters, activator proteins, and the mechanism of transcriptional initiation in yeast. PMID- 2882859 TI - In vitro transdifferentiation of striated muscle to smooth muscle cells of a medusa. AB - Mononucleated striated muscle cells can be isolated from anthomedusae and cultivated in artificial seawater. In the cultivated muscle the differentiated state is maintained and DNA synthesis is not observed. The isolated striated muscle can be activated by collagenase treatment to transdifferentiate into various new cell types. Between the second and third day following collagenase treatment DNA synthesis is initiated, and mitosis and de novo flagellum formation occur in the isolated muscle. Under these circumstances all isolated striated muscle fragments produce both smooth muscle cells and y-cells (Schmid and Alder, 1984). In experiments, in which either transcription (actinomycin D) or translation (cycloheximide) is inhibited, the activated striated muscle cells do not transdifferentiate but maintain their differentiated state. Inhibition of DNA replication (aphidicolin), however, results in uniform transdifferentiation of striated muscle to smooth muscle cells in the absence of y-cell types (Schmid and Alder, 1984). The fluorescence stain NBD-phallacidin is used to monitor the characteristic change of F-actin pattern of these isolates. PMID- 2882860 TI - Estrogen and antiestrogen modulation of the levels of mouse natural killer activity and large granular lymphocytes. AB - We investigated the time course of the 17 beta-estradiol effect on mouse natural killer (NK) activity and the number of splenic large granular lymphocytes (LGL), a cell population recently associated with natural cytotoxicity and enriched in low density fractions of Percoll discontinuous density gradients. After 7 days of in vivo treatment with estrogen, an increased cytotoxicity against YAC-1 lymphoma cells was observed using only as effectors cells recovered from higher density fractions, usually devoid of NK activity. In contrast, after a 30-day treatment, augmented NK activity and an increase in LGL number were observed in the lower density Percoll fractions. Similar results were observed after a 30-day treatment with the antiestrogen tamoxifen. The cytotoxicity of both low density and high density splenocyte fractions was totally abrogated by treatment with antiserum to asialo GM1 plus complement, whereas anti-Thy 1.2 antibody treatment only partially decreased the reactivity. Further estrogen administration up to 60 days decreased both NK activity and LGL number. It is concluded that estradiol can induce opposite effects on NK activity depending on the time of treatment, with stimulation of NK activity during the first 30 days after treatment followed by depressed NK activity 1 month later. PMID- 2882861 TI - Altered fatty acid membrane composition modifies lymphocyte localization in vivo. AB - In the present paper, we report the results of a study on the in vivo localization of 51Cr-labeled lymphocytes with an altered lipid bilayer. In vitro treatment of lymphocytes with fatty acids (arachidic and linolenic acids) modifies the relative composition of plasma membrane fatty acids. Phospholipids of the plasma membrane of lymphocytes incubated with arachidic acid show a preferential increase of fatty acids with chain length between C:12 and C:16. Cells incubated with linolenic acid show an increase percentage of fatty acids C:16 to C:20 and the relative amount of the fatty acids with chain length superior to C:20 is higher in cells treated with linolenic than with arachidic acid. We have found that these alterations in plasma membrane fatty acid composition can modify the normal pattern of lymphocyte localization in vivo after iv transfer into syngeneic hosts. The possible role of factors such as cell to cell adhesion and/or fluidity of plasma membranes in the control of lymphocyte migration are discussed. PMID- 2882862 TI - Redistribution of fluorescently labeled tubulin in the mitotic apparatus of sand dollar eggs and the effects of taxol. AB - Fluorescently labeled tubulin was quickly incorporated into the mitotic apparatus when injected into a live sand dollar egg. After a rectangular area (1.6 X 16 microns) of the mitotic spindle was photobleached at metaphase or anaphase by the irradiation of a laser microbeam, redistribution of fluorescence was almost complete within 30 sec. The photobleached area did not change in shape during the redistribution. During the period of redistribution, the bleached area moved slightly toward the near pole at metaphase and anaphase (means: 1.6 and 1.8 micron/min, respectively). These results indicate that redistribution was not due to the exchange of tubulin subunits only at the ends of microtubules but to their rapid exchange at sites along the microtubules in the bleached region. Furthermore, treadmilling of tubulin molecules along with the spindle microtubules possibly occurred at the rate of 1.6 micron/min at metaphase. Birefringence of the mitotic apparatus increased with a large increase in both the number and length of astral rays shortly after taxol was injected. However, the microtubules did not all seem to elongate at the same rate but appeared to become equalized in length. Chromosome movement stopped within 60 sec after the injection. Centrospheres became large and the labeled tubulin already incorporated into the centrospheres was excluded from the enlarged centrospheres. Shortly after the labeled tubulin was injected following the injection of taxol, it accumulated in the peripheral region of the centrospheres, suggesting that microtubules first assembled at this region. Fluorescently labeled tubulin in the mitotic apparatus in the egg after injection of taxol was redistributed much more slowly after photobleaching than in uninjected eggs. PMID- 2882863 TI - [A study on the feasibility of prenatal diagnosis of beta-thalassemia by DNA polymorphisms in the Chinese]. PMID- 2882866 TI - Baroreceptor function in congestive heart failure: effect on neurohumoral activation and regional vascular resistance. AB - A series of neurohumoral systems are activated in congestive heart failure that contribute to the increased vascular resistance and sodium retention that characterize this disorder. Abnormalities in baroreceptor function are intrinsic to the pathophysiology of heart failure and may subserve the vasoconstrictive and volume overloaded state that defines patient morbidity. Blunted baroreceptor responses to high cardiac filling pressures or depressed cardiac function reduce afferent signals that normally inhibit sympathetic efferent activity, vasopressin release, and indirectly, renin secretion. The resulting increase in neurohumoral activity mediates the redistribution of blood flow that occurs in this disorder. Limb blood flow is usually reduced and may be responsible for exercise intolerance. Decreased renal blood flow and altered intrarenal hemodynamics contribute to sodium retention. In addition, renal vasoconstriction and elevated circulating levels of angiotensin II and vasopressin may contribute to hyponatremia by influencing free water intake and excretion. Hence, baroreceptor dysfunction may be a principal mechanism that contributes to neurohumoral activation and subsequent alteration in vascular resistance and sodium and water balance in congestive heart failure. It may not be coincidental that two principal markers of an unfavorable prognosis in patients with heart failure, high plasma norepinephrine levels and hyponatremia, share baroreceptor dysfunction as a common theme. PMID- 2882865 TI - Influences on the distribution of blood flow during cardiac tamponade in the conscious dog. AB - Cardiac tamponade is a spectrum ranging from pericardial effusions with minimal hemodynamic impairment to effusions causing circulatory collapse. In this study, we examined the roles played by the sympathetic nervous system and the renin angiotensin system in controlling the distribution of blood flow in chronically instrumented conscious dogs during progressive cardiac tamponade. Fifty-one episodes of acute cardiac tamponade were induced to decompensation (decline in mean aortic blood pressure to 70% of the level present when the pericardium was free of fluid) in 6 dogs by intrapericardial infusion of warmed saline solution. Cardiac output (electromagnetic flow probe), intrapericardial pressure, aortic and right atrial blood pressures, and renal, coronary, and mesenteric artery blood flows (Doppler flow probes) were recorded during tamponade in the absence of blockade (control), during alpha-adrenergic blockade (phenoxybenzamine), beta adrenergic blockade (propranolol), or angiotensin-converting enzyme blockade (captopril). Aortic and mesenteric artery blood flow decreased progressively during cardiac tamponade regardless of the presence or absence of blockade. Coronary artery blood flow did not significantly change during alpha-adrenergic blockade, suggesting that the continuous decline observed during cardiac tamponade in the absence of blockade was at least in part mediated by alpha adrenergic mechanisms. Renal artery blood flow, in contrast, was well maintained in all situations, confirming the importance of autoregulation in this vascular bed during cardiac tamponade. PMID- 2882867 TI - Role of neurohormonal mechanisms in determining survival in patients with severe chronic heart failure. AB - Support for the concept that neurohormonal mechanisms play an important role in determining the survival of patients with severe chronic heart failure is derived from two lines of evidence: circulating levels of neurohormones are markedly elevated in patients who have a poor long-term prognosis and the survival of high risk patients may be favorably modified by treatment with specific neurohormonal antagonists. Plasma norepinephrine is a major prognostic factor in patients with severe chronic heart failure, the most markedly elevated levels being observed in patients with the most unfavorable long-term prognosis. Data from uncontrolled studies suggest that low-dose beta-blockade may improve the survival of patients with dilated cardiomyopathy. Similar trends were noted in the Beta-Blocker Heart Attack Trial, in which patients with congestive heart failure before or accompanying their acute myocardial infarction experienced a significant reduction in sudden death when treated with beta-blockers. In contrast, there appeared to be little selective benefit in patients without heart failure, who presumably had low circulating levels of catecholamines. Similarly, serum sodium concentration is a major prognostic factor in patients with severe chronic heart failure, the shortest survival being observed in patients with the most severe hyponatremia. The poor long-term outcome of hyponatremic patients appears to be related to the marked elevation of plasma renin activity in these individuals, since (in retrospective studies) hyponatremic patients appeared to fare significantly better when treated with converting-enzyme inhibitors than when treated with vasodilator drugs that did not interfere with angiotensin II formation. In contrast, there appeared to be no selective benefit of converting enzyme inhibition on the survival of patients with a normal serum sodium concentration, in whom plasma renin activity was low. These data suggest that neurohormonal systems may exert a deleterious effect on the survival of some patients with severe chronic heart failure, which may be favorably modified by long-term treatment with specific neurohormonal antagonists. PMID- 2882868 TI - Cardiovascular and neurohumoral postural responses and baroreceptor abnormalities during a course of adjunctive vasodilator therapy with felodipine for congestive heart failure. AB - Studies in patients with congestive heart failure (CHF) have demonstrated an abnormal beta-adrenergic reflex vasodilation during orthostatic tilt. Baroreflex modulation of vascular resistance in patients with CHF was investigated during therapy with a vasoselective calcium antagonist, felodipine. Eight patients on conventional therapy for severe CHF were studied after a 3 week course of additional felodipine or placebo treatment under randomized, double-blind, and crossover conditions. Forearm subcutaneous vascular resistance (FSVR) was estimated with use of the local 133Xe washout. Aortic pulsatile stretch, expressed as the systolic distension in percent of diastolic diameter, was calculated from echocardiographic measurements of aortic root diameters. At 3 weeks, felodipine reduced the arterial pressure, systemic vascular resistance, and FSVR, preserved cardiac filling pressures and heart rate, and increased cardiac output, stroke volume, and aortic pulsatile stretch. Upright tilt (45 degrees) was used to study baroreflex-mediated cardiovascular responses. The unloading of cardiopulmonary baroreceptors during upright tilt was substantial and about equal during both treatment courses, but the pulse pressure was maintained during the placebo and decreased during the felodipine period. During tilt, the patients on placebo failed to increase heart rate and their FSVR, systemic vascular resistance, and arterial mean pressure were decreased, whereas during tilt after felodipine, heart rate and systemic vascular resistance increased to maintain arterial mean pressure and FSVR also tended to increase. Both the stroke volume and aortic pulsatile stretch increased during tilt in patients on placebo but they decreased in those on felodipine. The tilt caused increments in circulating norepinephrine and epinephrine levels during both treatment regimens. Regulation of FSVR during the sympathetic stimulation of orthostatic stress was further elucidated. Proximal neural blockade caused an increase in FSVR during tilt in patients on placebo and a decrease in FSVR during tilt in those on felodipine. Local beta-adrenoceptor blockade caused similar increments in FSVR during tilt in patients on both treatments. Combined proximal and local blockade still increased FSVR during tilt in those on placebo, but caused no change in FSVR during tilt in those on felodipine. This study demonstrates that felodipine normalizes baroreflex control of vascular resistance in patients with CHF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882869 TI - A pathophysiologic basis for the clinical classification and management of unstable angina. AB - Recent clinical observations have extended our classification of unstable angina to include new groups of patients now recognized at high risk of subsequent infarction. Patients with non-Q wave myocardial infarction and those with early postinfarction ischemia share a prognosis similar to that of patients with crescendo angina or with acute coronary insufficiency. Unstable angina after coronary angioplasty and after coronary artery surgery also form particular subsets of patients. Pathologic, coronary angiographic, and coronary angioscopic studies have extended the role of the obstructive atherosclerotic plaque to include a dynamic component to explain the unstable state. Recognized dynamic components are rapid progression of the disease, active vasomotion, plaque fissuring, and thrombus formation. Activation of platelets and blood coagulation factors may play a major role in triggering the syndrome. Our therapeutic approach has also become more specific for the correction of the cause of the disease. Our understanding of unstable angina now appears to be at a turning point, and a pathophysiologic basis for its clinical classification and for its management may soon be available. PMID- 2882871 TI - The role of triple therapy in patients with chronic stable angina pectoris. AB - Despite the proven effectiveness of calcium-channel and beta-blockers as monotherapy in patients with chronic stable angina pectoris, some patients remain symptomatic. Such patients have been shown to benefit from the application of combined treatment with beta-blockers and nitrates or, more recently, beta blockers plus calcium-channel blockers. There have been few studies evaluating the long-term effectiveness of the combination of calcium blockers and nitrates, but available evidence suggests that symptoms of excessive vasodilation such as orthostatic hypotension may limit the usefulness of this approach. Recently, the additional benefit of adding a calcium blocker to therapy of patients with chronic stable angina who remain symptomatic on beta-blockers and nitrates has been demonstrated. Side effects related to vasodilation were the major limiting feature of this triple therapy. Thus, a triple therapy regimen may be of value in selected patients who do not respond to the combination of beta-blockers and nitrates or beta-blockers plus calcium blockers. However, caution must be exercised in patients with reduced left ventricular function and conduction system disease, since such patients have been excluded from the reported studies. PMID- 2882870 TI - Comparative effects of calcium entry-blocking drugs, beta-blocking drugs, and their combination in patients with chronic stable angina. AB - For monotherapy, beta-blockers and calcium-entry blockers are effective and safe antianginal medications. For prophylaxis of myocardial ischemia, a different mechanism of action for each class of drugs is reflected by the different heart rate and rate-pressure product during exercise. In patients who continue to have anginal symptoms despite adequate beta-blockade, further alleviation of symptoms together with an increase in exercise tolerance may be observed with the addition of a calcium-entry blocker. Of note is the individual patient response to the various calcium-entry blockers when combined with propranolol. Although of theoretic concern with combination therapy, no deleterious effect on left ventricular function or increased adverse clinical effects were noted in our studies. Combination therapy with beta-blockers and calcium-entry blockers is well tolerated, effective, and safe both over the short and long term in patients with exertional angina. PMID- 2882872 TI - Recognition, diagnosis, and prognosis of early reinfarction: the role of calcium channel blockers. PMID- 2882864 TI - Embryonal central neuroepithelial tumors: current concepts and future challenges. AB - While the embryonal central neuroepithelial tumors present complex conceptual and clinical problems, advances in cell type identification by special neurohistological, immunohisto- and immunocytochemical techniques have permitted discrimination of distinct cytomorphogenetic entities. These are based in part on their resemblance to the normal phases of neurocytogenesis. Four of these tumors, medulloepithelioma, desmoplastic infantile ganglioglioma, pineoblastoma and medulloblastoma, are designated as multipotential in light of their capacity to undergo divergent differentiation. Cytomorphogenetic, clinical and experimental data implicate fetal neural cell targets for transformation and raise the possibility that aberrant developmental regulatory mechanisms may contribute to the biologic behavior of these tumors. Growth factors and some neuroregulatory neurotransmitters (such as serotonin) are known to act as modulators of normal neuromorphogenesis. They could play a regulatory role in central neuroepithelial tumors on the hypothesis that the aberrant behavior of the embryonal neoplasms could either be modified by functional receptor responses or result from abnormal receptor responses to these substances. Future challenges include the definition of new cytomorphogenetic entities and subgroups of the currently defined forms of embryonal CNS tumors based on the presence of specific growth factors and neuroregulatory neurotransmitters, or their receptors, the characterization of neoplastic receptor responses mediating any modulatory role of the presently known growth factors or neuroregulatory neurotransmitters on the growth and maturation potential of the embryonal central neuroepithelial tumors and the further definition of developmental, stage-specific modulators that might be operative in these tumors. PMID- 2882874 TI - Drug interactions with the calcium-entry blockers. AB - The increasing use of the calcium-entry blockers has led to an enhanced potential for drug interactions with a variety of different drugs. Interactions with cardiovascular agents are of great concern because of the consequences of synergistic negative dromotropism or inotropism. We therefore assessed the concomitant use of calcium-entry blockers and cardiac glycosides, beta-blockers, antiarrhythmic agents, and other chemical types of calcium-entry blockers from a standpoint of clinical relevance. We also evaluated reported drug interactions with H2-receptor antagonists, anticonvulsants, lithium carbonate, general anesthetics, cytostatic drugs, rifampin, and sulfinpyrazone with regard to clinical implications, along with the modification of calcium-entry blocker dose for concurrent social drug use, such as cigarette smoking and ethanol intake. Although a myriad of potential drug interactions exists for these agents, combination therapy is still a reasonable alternative if doses are adjusted appropriately. PMID- 2882873 TI - Comparative studies of calcium-channel blockers and beta-blockers in essential hypertension: clinical implications. AB - The use of calcium-channel blockers to treat essential hypertension is increasing, and in the United States several new drug applications for this indication are under consideration by the Food and Drug Administration. Although the ability of the calcium-channel blockers to lower blood pressure has been established, their efficacy and safety in relation to current therapy require further clarification. This article reviews studies in which calcium-channel blockers and beta-blockers have been compared, including seven with verapamil, four with nifedipine and nitrendipine and two with diltiazem. These studies indicate that the two classes of agents produce similar antihypertensive effects and are associated with a comparable incidence of adverse reactions. In addition, the preliminary findings of a multicenter trial in which 50 subjects with mild or moderate hypertension were treated with diltiazem (60 to 180 mg bid) or propranolol (80 to 240 mg bid) for 4 to 6 months are presented. Both medications significantly lowered blood pressure (from 148 +/- 17/101 +/- 5 to 133 +/- 25/88 +/- 9 mm Hg on diltiazem and from 154 +/- 22/104 +/- 6 to 146 +/- 23/91 +/- 11 mm Hg on propranolol). Fifty-nine percent of the patients on diltiazem and 40% of those on propranolol achieved the treatment goal of a supine diastolic blood pressure under 90 mm Hg together with minimum 10 mm Hg reduction. In a similar study, exercise blood pressure and exercise capacity were also examined, with the most important finding being a reduction in maximal oxygen consumption and exercise duration on propranolol without a significant change on diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882875 TI - Vasodilators, antihypertensive therapy, and the kidney. AB - Whether or not the kidney is involved in the genesis of hypertension in an individual patient, it becomes a major determinant of the response to antihypertensive therapy once a treatment strategy is adopted. The major mechanisms through which the kidney influences blood pressure are renin release and sodium retention, either together or separately, but additional mechanisms may also contribute. When sodium intake is restricted or a diuretic is used, the reactive increase in plasma renin activity makes a substantial contribution to limiting the decrease in blood pressure. When vasodilators or agents that block the sympathetic nervous system are used, sodium retention plays an important role. Among newer agents, the effectiveness of calcium-channel blockers, converting-enzyme inhibitors, and perhaps dopamine analogs reflects, for reasons that differ from one class of agent to another, a special action on the kidney that limits the reactive renal response to the reduction in blood pressure. Treatment strategies that address the problem of the renal response are more likely to be effective than approaches that avoid or ignore it. PMID- 2882876 TI - A review of medical therapy for coronary artery spasm. AB - This article reviews controlled trials of medical therapy for coronary artery spasm. The calcium antagonists, either alone or in combination with long-acting nitrates, are effective therapy for patients with coronary artery spasm. These drugs definitely decrease angina and the frequency of ischemic ST shifts recorded during continuous electrocardiographic monitoring. Therapy is still relatively nonspecific, however, since the mechanism(s) that lead to spasm remain unknown. Interestingly, the initial response to therapy is similar regardless of the presence or absence of severe coronary artery disease accompanying spasm. Drugs that block adrenergic or serotonin receptors or that alter platelet aggregability or prostaglandin production have been ineffective in relieving angina or decreasing the frequency of ischemic ST shifts. Patients with resting angina syndromes are a heterogeneous group; many do not have coronary spasm since other mechanisms also precipitate ischemic episodes at rest. Prevention of angina or ischemic ST shifts may not necessarily prevent acute myocardial infarction and sudden cardiac death. Both initial and long-term therapies should be individualized according to a detailed clinical and angiographic assessments of each patient. PMID- 2882877 TI - Parenteral nutrition: short term effects on hepatic clearance of sodium taurocholate and indocyanine green. AB - Total parenteral nutrition (TPN) is thought to induce cholestasis. However, serum hepatic enzyme abnormalities were found in 70 percent of patients before TPN was started. Rate constants (alpha, beta, K(E] and total clearance (CIT) of sodium taurocholate (STC) and indocyanine green (ICG) were studied in 20 carefully selected patients not on TPN and who had no hepatic or renal disease. Clearance measurements were made prior to initiation and 7 days into dextrose-based TPN. Four modes of TPN administration were used; low calorie (35 cal/kg) versus high calorie (50 cal/kg), with or without protection of TPN solutions from ultraviolet light. Protein doses for all groups were isonitrogenous. TPN was uninterrupted and no patient had surgery, other major procedures, or food by mouth. While serum gamma-glutamyl transpeptidase (GGT) increased, no STC or ICG clearance parameter (total or subgroup) changed in response to TPN. These data do not support the hypothesis that TPN directly causes cholestasis, but suggest that cholestasis caused by concurrent liver disease may appear aggravated by TPN. PMID- 2882878 TI - Lectin-affinity chromatography of serum gamma-glutamyltransferase in liver disease. AB - The variation of the carbohydrate chain of gamma-glutamyltransferase was studied in 45 liver patients by means of lectin affinity chromatography. Five lectins were used: concanavalin A, Ricinus communis I and II, Maclura pomifera and Ulex europaeus agglutinin. The binding towards Con A was shown to be independent from the binding towards the other lectins. Parallel variations of binding results against the galactose- and fucose-recognizing lectins were obtained. In liver steatosis, the binding results were comparable to those obtained in normal patients. Cirrhosis and metastasis patients showed a decreased binding towards Con A, while the binding against the various galactose- and fucose-recognizing lectins was increased. After neuraminidase treatment, an increased affinity towards all lectins was observed. However, differences in RCA I and RCA II binding between patients and controls still persisted. Besides sialic acid, also galactose and fucose residues contribute to serum gamma-glutamyltransferase heterogeneity. PMID- 2882880 TI - Prenatal diagnosis in Becker muscular dystrophy. AB - Prenatal diagnosis in a pregnancy at risk for Becker muscular dystrophy is reported. The diagnosis was made prior to 12 weeks of gestation by typing a CVS sample for DNA markers. PMID- 2882879 TI - Human erythrocyte gamma-glutamyltransferase in liver diseases. AB - The gamma-glutamyltransferase activity of erythrocytes was estimated in healthy adults and in patients with hepatobiliary disease. Control activity was 1.97 +/- 0.70 X 10(-4) U/mg ghost protein. Activity was elevated to 8.54 +/- 7.81 X 10(-4) U/mg in patients with hepatobiliary disease. Very high values, above 15 X 10(-4) U/mg were seen in patients with primary and secondary liver carcinoma, and also in some patients with obstructive jaundice. The erythrocyte enzyme had the same kinetic properties as serum and liver enzymes and was inhibited by serine-borate mixture, a specific inhibitor of the enzyme. There was no correlation between the erythrocyte enzyme level and either plasma hydrophobic enzyme level or erythrocyte glutathione content. PMID- 2882881 TI - An abnormal pattern of amniotic fluid microvillar enzymes signalling fetal cystic fibrosis. AB - We have observed seven pregnancies at risk for fetal cystic fibrosis where second trimester amniotic fluid microvillar enzyme activities presented an unusual pattern. Low gamma-glutamyltranspeptidase and borderline alpha-glucosidase values were associated with normal aminopeptidase M and intestinal alkaline phosphatase values. All seven pregnancies went to term; five of the seven infants were affected with cystic fibrosis. PMID- 2882882 TI - Assignment of the locus order DXS28-DXS67-DMD as a spin-off from diagnostic DNA marker analysis in a family with Duchenne muscular dystrophy. AB - During diagnostic segregation analysis for seven DNA markers, linked to and flanking the locus for Duchenne muscular dystrophy (DMD), a family was identified in which a boy with a recombinant X chromosome had inherited his maternal grandmother's alleles at the loci DXS43 (D2/Pvu II) and DXS28 (C7/Eco RV), and his maternal grandfather's alleles at DXS67 (B24/Msp I) and DXS84 (754/Pst I). Combined with earlier data this finding strongly suggests the locus order DXS28 DXS67-DMD. Another recombination event, identified in the same family, supports the previously established order DMD-DXS84-OTC. The diagnostic importance of flanking markers, and the likelihood of false diagnostic conclusions due to possible double crossovers, with and without demonstrable neighbouring single crossover events, are discussed. PMID- 2882884 TI - DNA molecular biology in the diagnosis of pulmonary disease. AB - DNA molecular biology is becoming increasingly important in clinical medicine. It has provided a new method to diagnose an inherited pulmonary disease in which the biochemical defect has been defined. Alpha-1-antitrypsin deficiency can now be diagnosed by direct analysis for the disease gene. In cystic fibrosis, another inherited pulmonary disease, the biochemical defect has not yet been defined. However, the search has been narrowed. The cystic fibrosis genetic defect has recently been localized to the long arm of chromosome 7. Because polymorphic DNA markers (RFLPs) are available for this region of chromosome 7, it is now often possible, using linkage analysis, to trace the inheritance of the cystic fibrosis gene(s) in families known to have cystic fibrosis. When the cystic fibrosis genetic defect is defined, it will then be possible to look directly for the disease gene. Finally, the greatest impact in clinical medicine may well be the development of rapid DNA hybridization techniques to diagnose infectious diseases that currently take days to weeks to diagnose. PMID- 2882883 TI - Bromazepam pharmacokinetics: influence of age, gender, oral contraceptives, cimetidine, and propranolol. AB - Pharmacokinetics of the benzodiazepine bromazepam were evaluated in volunteer subjects who received single 6 mg oral doses followed by blood sampling during the next 48 hours. Age and gender effects were studied in 32 subjects, divided into young (aged 21 to 29 years) and elderly (aged 60 to 81 years) groups. Compared with young subjects, the elderly had significantly higher peak serum bromazepam concentrations (132 vs. 82 ng/ml), smaller volume of distribution (0.88 vs. 1.44 L/kg), lower oral clearance (0.41 vs. 0.76 ml/min/kg), and increased serum free fraction (34.8% vs. 28.8% unbound). However, gender had no significant influence on bromazepam kinetics. In 11 young female users of oral contraceptive steroids, compared with seven age- and weight-matched control women not using oral contraceptives, no differences in bromazepam kinetics were observed. Coadministration of cimetidine (1.2 gm daily) significantly reduced bromazepam clearance (0.41 vs. 0.82 ml/min/kg) and prolonged elimination half life (29 vs. 23 hours). Propranolol (160 mg daily) significantly prolonged bromazepam half-life (28 vs. 23 hours), but the reduction in clearance associated with propranolol (0.65 vs. 0.82 ml/min/kg) did not reach significance. Bromazepam has the pharmacokinetic characteristics of benzodiazepines with half-life values between 20 and 30 hours. Consistent with its biotransformation pathway by hepatic microsomal oxidation, bromazepam clearance is significantly impaired in elderly individuals, by coadministration of cimetidine and possibly propranolol. PMID- 2882885 TI - Medical management of stable angina pectoris. PMID- 2882886 TI - Recognition and management of myocardial ischemia. PMID- 2882887 TI - New directions for hypertension therapy. PMID- 2882888 TI - Comparative model analysis of central shunts in vertebrate cardiovascular systems. AB - The incomplete double circulation of air-breathing fishes and lungfishes, amphibians, reptiles and embryonic birds and mammals has been analyzed using a simplified mode comprising the intra- and extracardiac shunts and compartments for the gas exchange (gills, lungs, skin, etc.) as well as systemic tissue gas exchange. The intracardiac shunting is defined and given common symbols for all species of animals analyzed. Two types of equations, fluid-flow and mass-flow equations, are derived for each model, which are solved to give shunting rate as a function of blood O2 content of the principal cardiac compartments and vessels. The model analysis not only offers possibility for an overall average evaluation of central shunts, but also suggests which blood samples must be determined for evaluation of the shunt patterns. PMID- 2882889 TI - Frogs and turtles: different ectotherm overwintering strategies. AB - The ability of frogs and turtles to overwinter and to survive hypoxia and anoxia has long been a topic of interest. While data remains scant, the emerging picture shows fundamentally different approaches to overwintering in these two groups of ectotherms. Frogs are far more limited by availability of oxygen than are turtles, even at near-freezing ambient temperatures. The reasons for this probably involve the vastly greater cutaneous permeability of the former. With their extreme tolerance of anoxia and profound suppression of metabolism, overwintering in turtles should not be viewed as simply prolonged diving but rather as ectotherm hibernation. Their incredible diving capabilities are merely a spin-off of a successful overwintering strategy. The following discussion reviews the major physiological mechanisms involved in the overwintering strategies of these two ectotherm groups. PMID- 2882890 TI - Age influences on intestinal sugar absorption. AB - Intestinal absorption of sugars show differences depending on animals age. This is demonstrated using in vivo and in vitro techniques. The age dependence relationship is present in animals of different species such as avian, rodents and ruminants. In chicken the intestinal sugar transport increases after hatching and attains its maximum capacity by the first week of life. The D-glucose and D galactose uptake is greater in young rats, maximum at 21 days, while it decreases thereafter. The total capacity of the small intestine of adult sheep for sugar absorption was approx. 25% of that for lambs less than 1 week of age. The differences observed in intestinal absorption of sugars at different ages could be attributed to differences in sodium and calcium transport. Other authors assume that it is induced by morphological differentiation during intestinal development. PMID- 2882891 TI - Jejunal and cecal 3-oxy-methyl-D-glucose absorption in chicken using a perfusion system in vivo. AB - 3-oxy-methyl-D-glucose (3-OMG) absorption by jejunum and caecum has been studied in the domestic fowl in vivo, with luminal perfusion, during 5 min periods. The diffusion component was evaluated in the presence of phloridzin (10(-3) M) that inhibits the active transport mechanism. Kd of jejunal and cecal diffusion of the monosaccharide have been calculated, showing a similar value. The Kt and Vmax of 3-OMG absorption were calculated using a graphical method for the two intestinal segments. The caecum showed a lower Kt and Vmax than the jejunum did. PMID- 2882892 TI - Changes in nonspecific immunity factor in some Equidae, Camelidae and Capridae species. AB - Plasma lysozyme activity changed during the 2 years of the investigation period. In some species (e.g. ponies and goats) there are only seasonal fluctuations with the highest levels during summer and autumn in ponies and during winter in goats. In two Camelidae species, guanacos and llamas, only, downward trends were found, whereas in donkeys, both types of changes: seasonal variations with the maximal level during autumn and an upward long-term trend were found. PMID- 2882893 TI - Metabolism and thermoregulation in two races of Djungarian hamsters: Phodopus sungorus sungorus and P. s. campbelli. AB - Two races of Djungarian hamsters (Phodopus sungorus sungorus and P. s. campbelli) differ in their responses to low ambient temperatures. The lowest temperature tolerated is 6-10 degrees C higher in P. s. campbelli than in P. s. sungorus, both in summer and in winter, but the highest (Vo2-max) and lowest (BMR) metabolic rates are similar in both subspecies. Body temperature and overall conductance in the cold appear to be more variable in P. s. campbelli than in nominative sp. PMID- 2882894 TI - Basic haematological values in carnivores--I. The Canidae, the Hyaenidae and the Ursidae. AB - Basic haematological values for 32 animals of four carnivore species are reported. In six adult wolves (Canis lupus) the mean values estimated for the erythrocyte count 7.48 X 10(12)/l, haematocrit 0.465/l, haemoglobin 172.0 g/l and leukocyte counts 7.33 X 10(9)/l are given. For five young wolves, these parameters were markedly decreased, only the white cell count was raised. In 14 hunting dogs (Lycaon pictus) the mean values estimated are: erythrocyte count 9.15 x 10(12)/l haematocrit 0.435/l, haemoglobin 179.2 g/l and leukocytes 12.95 X 10(9)/l. In six striped hyaenas (Hyaena hyaena) the mean estimated values are: erythrocyte count 8.11 X 10(12)/l, haemoatocrit 0.445/l, haemoglobin 178.0 g/l and leukocytes 13.95 X 10(9)/l. Only individual values for the reported parameters are given in the Asiatic black bear (Selenarctos thibetanus). All results are compared with values derived from the literature for animals under investigation and for the domestic dog (Canis familiaris). PMID- 2882895 TI - Studies on the absorption of sodium and chloride from the rumen of sheep. AB - The net absorption of Na and Cl from the temporarily isolated rumen of sheep was studied using an artificial ruminal fluid with different Na and K and constant Cl concentrations. The net absorption of Na and Cl was linearly correlated. The net absorption of Cl was abolished and a small net secretion was observed when no sodium was in the artificial rumen fluid. The net absorption of Na was significantly reduced under chloride free conditions. It is concluded that the active transport of Na and Cl is coupled. The mechanism of an Na-Cl cotransport can not be deduced from these studies. PMID- 2882896 TI - Effects of plasma aldosterone on butyrate absorption and metabolism in the rabbit proximal colon. AB - Butyrate absorption in the proximal colon of the anaesthetized rabbit was evaluated by measuring the variations in the concentration of butyrate in colonic loops and in arterial and venous plasmas; metabolic conversions were studied using (3,4-14C) butyrate. Interrelations between butyrate absorption and metabolism and the excretory cycle of the rabbit were examined, as well as the effects of exogenous aldosterone, the hormone generally implicated in the diurnal rhythm of the fecal excretion. The colonic tissue metabolized butyrate via 2 main pathways. They were of differing intensity according to the 2 phases of the excretory cycle. When the plasma level of aldosterone was high (during hard faeces production), the butyrate was mainly oxidized to CO2, yielding energy for metabolic processes. When the plasma level of aldosterone was lower (during soft production), butyrate was also oxidized to CO2 but it was a better source of free amino acids. Exogenous aldosterone (30 micrograms/kg) enhanced absorption and oxidative metabolism of the butyrate, which occurred normally when hard faeces were elaborated. PMID- 2882897 TI - Effect of colchicine on some electrical properties of rat small intestine. AB - The effect of colchicine on the short circuit current (s.c.c.), potential difference (p.d.) and tissue resistance was investigated in vitro using rat jejunum. The electrogenic transfer of glucose, galactose, glycine and valine was also measured in the presence and absence of the drug. Colchicine (0.05 mM and 0.1 mM) caused a dose-dependent decrease in s.c.c. and p.d. in the presence of glucose but had no significant effect on the tissue resistance. Colchicine at (0.1 mM) increased the "apparent Km" of glucose (140% P less than 0.001) galactose (135% P less than 0.001) glycine (43% P less than 0.001) and valine (47% P less than 0.001) but had no significant effect on the p.d.max of these substrates. PMID- 2882898 TI - Carbonic anhydrase activity in the blood of adult sheep, fetal sheep and lambs. AB - The activity of carbonic anhydrase (E.C.4.2.1.1) (CA) has been measured in the blood of adult and fetal sheep and lambs. The mean activity in adult sheep was 0.89 enzyme units (EU) per 100 micrograms of Hb. The activity in fetal sheep aged 90 days was just below 20% of this and in fetuses near full term was just under 40% of the mean adult level. The regression line gave an increase of CA activity (per 100 micrograms Hb) of 0.004 EU/day. The appearance of CA in fetal blood normally occurred before any detectable production of adult Hb. One aberrant fetus showed early development of the adult pattern in the red cells, having adult type Hb and adult levels of CA during the period of 116-128 days of fetal age. In the period after birth the CA level in the blood rose rapidly, reaching the adult level 30 days after birth. During this period activity per 100 micrograms HB increased by 0.014 EU/day, significantly faster than during fetal life. PMID- 2882899 TI - Dimer-tetramer transition in hemoglobins from Liophis miliaris--I. Effect of organic polyphosphates. AB - Hemoglobin from the water-snake Liophis miliaris in the stripped form presents high oxygen affinity of about P50 = 1 mmHg and Hill coefficient of about 1.0 at pH from 6.8 to 8.5. In the presence of ATP such values become P50 = 20 mmHg and nH about 2.0, respectively, at low pH from 6.5 to 7.5. When the pH increases an abrupt decrease of both P50 and nH values occurs falling close to those found for the stripped hemoglobin. Gel-filtration in Sephadex G-100 equilibrated with 0.05 M Tris-HCl buffer containing 1 mM EDTA of the stripped hemoglobin show the presence of only one component of mol. wt of about 32,500 dt similar to the dimer of human hemoglobin A. The deoxy form of the dimer previously treated with ATP and placed on Sephadex column in the same condition but containing 1 mM IHP emerges as tetramer with mol. wt similar to that found for human hemoglobin, i.e. of about 65,000 dt. Results of the multiplicity of the snake hemoglobin, as well as the large alkaline Bohr effect in the presence of ATP previously reported, seems to be inconsistent due to the dimer-tetramer transition that occurs when ATP is bound to the stripped hemoglobin. A molecular mechanism involving the dimer-tetramer transition is proposed to described the oxygen transport in these animals. PMID- 2882900 TI - Ontogenic screening of aldosterone in the South American toad Bufo arenarum (Hensel). AB - The content of aldosterone in the South American toad Bufo arenarum embryos developed in Holtfreter's 10% solutions and in distilled water was measured. The screening was carried out on embryos from the following periods of their development: 15 min after fertilization; gray crescent-32 cells; mid cleavage late gastrula; neural plate-neural tube; tail bud-heart beat; gill circulation tail fin circulation and operculum fold-complete operculum. The aldosterone content of embryos incubated both in Holtfreter and in distilled water decreased gradually up to gill circulation-tail fin circulation stages. The steroid content of both groups of embryos rose sharply at the end of their development (operculum fold-complete operculum); the observed increase was significantly higher in distilled water animals. PMID- 2882901 TI - Ca2+-induced Ca2+ release in skinned single smooth muscle cells isolated from guinea-pig taenia caeci. AB - The Ca2+ release from intracellular Ca2+ storage sites of skinned single smooth muscle cells isolated from guinea-pig taenia caeci was studied. The Ca2+ release from intracellular Ca2+ storage sites of the skinned single cells was enhanced by the presence of submicromolar concentrations of Ca2+ in the solution. The Ca2+ release was enhanced by caffeine and adenine, and suppressed by Mg2+ and procaine. These results suggest that the Ca2+-induced Ca2+ release mechanism may play an important role in the release of Ca2+ from intracellular storage sites of guinea-pig taenia caeci smooth muscle cells. PMID- 2882902 TI - Cellular composition of the bone marrow in the chicken, a comparison of femur, tibia and humerus. AB - A comparison of cellular composition of marrow from femur, tibia and humerus was made at hatch and at 3, 4, 6, and 12 weeks of age. There were no significant differences between femoral, tibial, and humeral marrow in relative and absolute cell numbers, mitotic indices or thymidine uptake. However, the cellularity per mg of marrow was consistently lower for the humerus than it was for the femur and tibia. There was a significantly greater frequency of immature granulocytes in the femur and tibia at hatch than at 4 weeks of age. PMID- 2882903 TI - Urate and p-aminohippurate transport in isolated kidney tubules of normal and hyperuricemic chickens. AB - Urate and p-aminohippurate accumulations of kidney tubule fragments were studied in 5- to 6-week-old normal (LUA) and hyperuricemic (HUA) chickens. Tubules from LUA chicks consistently accumulated two to three-fold as much urate and p aminohippurate as tubules from HUA chicks and thus confirmed the tubular origin of the urate transport defect in HUA chickens. A sodium gradient was required for optimal urate and p-aminohippurate accumulations and ouabain inhibited the accumulations of both compounds. Similar responses of urate and p-aminohippurate to treatments and reciprocal inhibitions between these compounds suggest that urate and p-aminohippurate are accumulated through a shared transport system. PMID- 2882904 TI - Few intra-lake variations of physiological parameters in perch, Perca fluviatilis. AB - Intra-lake variations in physiological parameters, representing haematology, plasma ion composition and carbohydrate metabolism, were investigated in perch (Perca fluviatilis), inhabiting a comparatively unpolluted lake. Provided the perch were subjected to a standardized procedure for capture, handling, recovery after capture, and sampling, only few and minor differences were observed in 21 parameters investigated when 3 groups were compared to a control group of perch. It is concluded that the experimental design used is suitable for the examination of the physiological status of perch in the field. PMID- 2882905 TI - Concerning stimulation by high external potassium and calcium injection of the ouabain-insensitive sodium efflux in barnacle muscle fibers. AB - The behavior of the ouabain-insensitive Na efflux in barnacle muscle fibers toward external high K and injection of Ca2+ has been further investigated. Raising Ke to 100 mM after the injection of 0.25 M or 0.1 M GTPNa2 results in a biphasic stimulatory response: the initial response is prompt in onset and small but transitory, whereas the delayed response is large and sustained. This second stimulatory phase is reduced markedly by injecting EGTA but not by PKI. Raising Ke to 100 mM in the presence of the 2 xanthine derivatives, viz. PMX and IAX, leads to a sustained stimulatory response of the ouabain-insensitive Na efflux which is halved by injecting PKI but unaffected by injecting EGTA. Injection of 0.1 M or 0.5 M CaCl2 in the presence of PMX and IAX leads to a sustained stimulatory response, which is almost completely abolished by injecting PKI but unaffected by injecting EGTA. These results confirm the earlier finding that the response of the ouabain-insensitive Na efflux to high Ke in fibers preinjected with GTPNa2 is biphasic and that the delayed second stimulatory phase is sustained rather than transitory. The ability of injected EGTA to only partially reverse the delayed response suggests that a fall in myoplasmic pCa is not the sole factor governing the kinetic picture. The experiments with PMX and IAX strongly suggest that cAMP is involved in the termination of the Ca2+ message. PMID- 2882906 TI - The posthatch physiology of the turkey poult--I. Growth and development. AB - Daily body, heart, liver, spleen, pancreas and bursa of Fabricius weights of developing turkey poults were measured. Neither organ nor body weight was affected by sex of the poults during the first 10 days posthatch. Decreases in growth were apparent between days 3 and 6 or 7 and 9 posthatch and coincided with peaks in early mortality. PMID- 2882907 TI - The posthatch physiology of the turkey poult--II. Hematology. AB - Packed cell volume, total leukocytes, total erythrocytes, hemoglobin, mean cell volume and mean corpuscular hemoglobin concentration of the poult were analyzed daily for the first 10 days posthatch. Sexually dimorphic effects on hematological parameters were not apparent, but there was a sex X day interaction for all parameters except hemoglobin indicating that males were slower to develop/respond to critical stimuli. The study revealed a latency in production of erythrocytes and leukocytes in posthatch males and females which coincided temporally with early poult mortality. PMID- 2882908 TI - Vitamin A levels of blood in collared peccaries (Tayassu tajacu) from south Texas. AB - Serum vitamin A concentrations were determined for 24 adult female collared peccaries from 1 captive and 2 wild populations during the period 30 January-15 March, 1983. Normal serum vitamin A concentrations of well-fed captive peccaries (mean = 39.0 micrograms/dl) were slightly higher than the reported range of values for domestic swine. Mean vitamin A concentrations of blood serum did not differ among the captive and 2 wild populations. However, a few individuals from the wild populations had low serum levels of vitamin A which suggested a possible vitamin A deficiency for these females. PMID- 2882909 TI - Evolution of the sensitivity of isolated adipocytes of ewes to the antilipolytic action of adenosine during pregnancy and lactation. AB - Four successive biopsies of omental adipose tissue were performed on the 43rd, 100th, 140th days of pregnancy and during the 3rd week of lactation in 6 "Pre Alpes" ewes. Using incubated isolated adipocytes, we studied the evolution of the antilipolytic effect of adenosine. Adenosine presented a significant inhibitory effect on basal lipolysis only at the end of pregnancy. The antilipolytic effect of adenosine on the stimulated lipolysis by a beta-agonist (isoproterenol 400 nM) increased during pregnancy. The maximal effect was observed 1 week before parturition. The level of inhibition remained high during lactation. The lipolytic effect of adenosine-deaminase was enhanced during pregnancy and lactation and evolved similar to the observed action of adenosine. Results suggest that the antilipolytic action of adenosine may have a physiologic importance. PMID- 2882910 TI - Assessment of the sexual and antler potential of the male white-tailed deer (Odocoileus virginianus) by Gn-RH stimulation test. AB - Twelve mature white-tailed bucks were injected with gonadotropin regulating hormone (Gn-RH, 100 micrograms/deer) during the rut (November) and during the spring (April). In the rut, superior bucks (with actual or potential large body weight, trophy antlers and a high social rank) responded to Gn-RH with a small increase of LH (below 20 micrograms/ml) and a profound rise in testosterone (T) (30-50 ng/ml). The inferior animals exhibited high increase of LH (30-40 ng/ml) but a low rise in T (below 10 ng/ml). FSH levels increased only slightly after Gn RH and the concentrations were not related to reproductive performance. During the spring, increase in LH levels after Gn-RH administration greatly exceeded the rise of T, but no relationship was found between hormonal levels and the reproductive potential. FSH levels increased remarkably after Gn-RH administration. Gn-RH (administered during the rut) might be used for assessment of the potential for reproductive and antler performance. PMID- 2882911 TI - Antidepressant drugs: imipramine, mianserin and trazodone. AB - The advent of newer antidepressant drugs (second generation) during the past two decades has provided an alternative to the use of tricyclic antidepressants in the alleviation of depression. These antidepressants have not been proven to be superior in the therapy of depression to the tricyclic antidepressants but they have been reported to cause fewer cardiac effects. Most of the reported adverse cardiac reactions elicited by antidepressant drugs are based on observations from clinical studies. The possible underlying mechanisms by which these adverse reactions arise have for the large part been proposed on the basis of clinical findings which have been extrapolated back to the known pharmacological actions of such drugs. There is a paucity of hard experimental data in this respect. PMID- 2882912 TI - Review and perspective on the use of mixed-function oxygenase enzymes in biological monitoring. AB - It is often suggested that changes in simple biochemical/physiological responses may be useful for predicting the impacts of pollutants at population and community levels of biological organization. There are serious conceptual constraints to such a thesis and its seems likely that such simple responses can go no further than serving as early warning systems for delineating potential areas of pollutant impact--areas which (if shown to be significant in size) can then be subjected to more detailed population and community type studies. Environmental testing is a prerequisite for any response suggested to have value as a biological monitoring index and the induction of mixed-function oxygenase (MFO) enzymes has now been validated in a large number of field studies worldwide. Investigations have progressed from documenting induction near localized sources of hydrocarbon contamination to more diffuse sources of mixed organic pollution originating from industrial and domestic sources. Studies in the Great Lakes and Europe have demonstrated that the induction of MFO enzymes is a biological response of sufficient sensitivity to discriminate water quality differences over broad geographical areas. We suggest that as an early warning system, the induction of these enzymes can fulfill the requirement of "most sensitive biological response" for assessing a variety of organic pollution conditions. Given the high level of sensitivity of the MFO enzyme response, negative as well as positive field trials can be of value in addressing concerns about the toxicological significance of "high-profile" chemicals (and potent inducers) such as polycyclic aromatic hydrocarbons and organochlorines. MFO enzyme induction can also be an economical tool for environmental managers for reacting to real or perceived concerns about pollution such as effects on commercial fish stocks at sites of petroleum hydrocarbon development in the oceans. PMID- 2882913 TI - Acute and chronic toxicity of nitrite to Clarias lazera. AB - The present study is an attempt to define acute (96 hr) and chronic (6-months) effects of nitrite on two different sizes of juvenile Clarias lazera. Static bioassays on acute toxicity showed median tolerance limit (TLm) for four days of 28 and 32 mg/l NO2-N for the two sizes respectively. Although nitrite is known to cause hypoxia, as a result of oxidation of haemoglobin to methemoglobin, exposure of both sizes to nitrite resulted in a decreased erythrocyte count haemoglobin content and haematocrit values. Fish exposed to nitrite responded physiologically by producing methemoglobin. A decline in serum total protein levels was recorded during acute and chronic exposure of both sizes to nitrite. This was interpreted as a generalized stress response. PMID- 2882914 TI - Serum transaminases activity and histopathological changes in Clarias lazera chronically exposed to nitrite. AB - Increase in serum transaminases (GOT and GPT) activity attributable to nitrite toxicity was observed in juvenile Clarias lazera after chronic exposure to nitrite. The application of SGOT and SGPT assays for monitoring the effect of nitrite exposure over a 6-month period has shown that changes in activities are correlated with histological effects in Clarias liver. Kidneys from fish exposed to nitrite were not noticeably different histologically from that of control fish. Hypertrophy and hyperplasia were the most consistent lesions that occurred in the gills. Lifting of lamellar epithelium and necrosis of some epithelial cells were also prominent. PMID- 2882916 TI - Cd-metallothionein and metal-enzymes interactions in the goldfish Carassius auratus. AB - Goldfish injected with cadmium chloride synthesized metallothionein. Ten days after the first injection, cadmium reached a maximum in the metallothionein peak (2 micrograms/ml) obtained after gel filtration of liver cytosol. Pyruvate kinase activity was inhibited from the beginning of the experiment; after the fourth day, the enzyme activity again started to increase but did not reach the control level. Alkaline phosphatase and fructose biphosphatase did not show any apparent inhibition. From the results here reported, a detoxifying role of metallothionein could be suggested. PMID- 2882915 TI - Toxicity in Tilapia zilli and Clarias lazera (Pisces) induced by zinc, seasonally. AB - Subadult teleosts, Tilapia zilli and Clarias lazera, were exposed in laboratory bioassays to lethal and sublethal concentrations of zinc, seasonally (at range of temperature between 9.3 +/- 1.5 and 25 +/- 1 degree C). It appears that Tilapia is more susceptible to Zn than Clarias and both species are more resistant to Zn toxicity at lower temperature (during winter). To determine the uptake and tissue distribution of Zn in the two species, gill, liver and muscles were analysed at moderate temperature (during spring). After a 96 hr exposure period, Zn was decreased in the following order: gill greater than liver greater than muscle. PMID- 2882918 TI - Control of ciliary beat frequency in the gill of Mytilus--II. Effects of saponin and Brij-58 on the lateral cilia. AB - The effects of saponin and Brij-58 on the beat activation of the lateral cilia on the gill of Mytilus edulis were investigated. The ciliary activation by 5 hydroxytryptamine (5HT) decreased as the saponin-induced permeabilization progressed, increasing the reactivation of the ciliary beat by extracellularly applied ATP (1 mM). The cilia were activated by 5HT even after the treatment with saponin (0.01 and 0.02% w/v) or Brij-58 (0.07%) rendered the preparation capable of the reactivation by ATP. The saponin treatment itself stimulated the beat of the cilia. Theophylline (1 mM) augmented the saponin-induced activation of the cilia. PMID- 2882917 TI - Control of ciliary beat frequency in the gill of Mytilus--I. Activation of the lateral cilia by cyclic AMP. AB - The effect of cyclic AMP on the beat frequency of the lateral cilia on the gill of Mytilus edulis was investigated. Dibutyryl cyclic AMP (0.1 mM) weakly stimulated the cilia to beat. The activation was augmented by 1 mM theophylline. The cilia were hardly activated by cyclic AMP (0.1 mM) but a strong activation was observed when it was applied with saponin (0.0025-0.01% w/v) and theophylline (1 mM). The results suggest that cyclic AMP is involved in the mechanism of ciliary activation by 5-hydroxytryptamine. PMID- 2882919 TI - Factors in the accumulation of dieldrin in broiler organs: doses administered with feed; dose-organ-dieldrin accumulated relationship; toxicological consequences. AB - The quantity of dieldrin accumulated in liver, kidney, heart, gizzard, lung, muscle, and intestine with contents, of broiler chickens fed with feed contaminated by this insecticide, was determined by gas chromatography analysis. The doses used were 60, 90, 120, 200 and 240 ppm. The influence of the doses used in the quantity of dieldrin accumulated in the different organs, the relationship between the doses administered, organs and quantity accumulated, and the toxicological consequences of the contamination were studied. The results show that the doses used did not significantly affect the quantity of dieldrin accumulated by the different organs. The relationship doses-organ-quantity accumulated shows that the muscle accumulates equal dieldrin at all the doses used. The differences in the dieldrin accumulated at different doses increases with the metabolic function of the organs. The principal symptoms of intoxication were anorexia, convulsions and tremors, which indicated that the nervous system is a major site of activity. PMID- 2882920 TI - Possible interaction of the adrenal-gonadal systems on brain catecholamines of adult male rats. AB - Studies from this laboratory showed that gonadectomy (GDX) alters biogenic amines concentrations in diencephalon during the first 40 days. While the GDX females maintain the differences at day 60, the differences are eliminated in males at that time. In the present work, we have studied in three cerebral regions the adrenal involvement in the mechanism responsible for this normalization of catecholamine concentration in long-term castrated adult male rats. A hypersecretion of adrenal steroids seems to compensate for the lack of gonadal effect when the orchidectomized rats reach adulthood only for diencephalic dopamine. PMID- 2882921 TI - Influence of sexual differentiation on striatal and limbic catecholamines. AB - The influence of sexual differentiation of the brain on catecholamine content in the corpus striatum and limbic system was studied. Our results suggest that circulating ovary hormones during the critical period play an important role in the sexual differentiation of dopaminergic neurons in the corpus striatum and limbic system. Absence of androgenic steroids in the critical period leads to permanent alterations in the DA content of the limbic system in the male rat. Gonadectomy does not significantly alter NA levels in either of the two studied brain areas. PMID- 2882922 TI - Pharmacology of GABA receptors on skeletal muscle fibres of the locust (Schistocerca gregaria). AB - GABA and the trans isomer of 4-aminocrotonic acid are equally potent at inducing increases in Cl- conductance when applied to distal extensor tibia muscle fibres of the locust (Schistocerca gregaria). beta-Alanine, norvaline, glycine and norleucine induced conductance increases of less than 5% of GABA responses. C9 and meso-di-GABA did not alter input conductance in a manner consistent with actions on a GABA receptor Cl- channel complex. Picrotoxin and anisatin were equally potent GABA antagonists, however bicuculline and penicillin G did not reduce GABA-induced changes in input conductance. Pentobarbitone, in addition to inducing an increase in K+ conductance, potentiated GABA-induced increases in Cl- permeability. PMID- 2882923 TI - The muscarinic receptor-mediated action of acetylcholine in the gastrulating chick embryo. AB - Some of the muscarinic receptor-mediated effects of acetylcholine in early chick embryo cells at stages three-four by Hamburger and Hamilton were studied. Acetylcholine increased the intracellular level of cGMP about two-fold. Acetylcholine raised the intracellular level of free calcium from the basal level of 120 nM to 140 nM. Atropine, a muscarinic antagonist, blocked both the above mentioned responses. PMID- 2882924 TI - Modulation of dopamine receptors in the Tapes clam by dextroamphetamine and phenylethanolamine. AB - The mechanism underlying the modulation, by dextroamphetamine and compounds related to phenylethanolamine, of responses to dopamine and serotonin has been studied in the isolated ventricle and aortic bulb of the clam Tapes watlingi. Dextroamphetamine and phenylethanolamine but not cocaine and benztropine have the ability to unmask inhibitory responses to both dopamine and serotonin in the ventricle. Chlordimeform but not clozapine attenuates the inhibitory response to both dextroamphetamine and phenylethanolamine in concentrations which have little or no effect on the inhibitory response to dopamine in the ventricle. Phenylethanolamine, dextroamphetamine, phenylpropylolamine and p-chloro phenylethanolamine but not octopamine or noradrenaline attenuate the contractile responses to both dopamine and serotonin in preparations of the quiescent aortic bulb. These data show that there are specific receptors for phenylethanolamine in the Tapes heart capable of modulating responses to dopamine and serotonin, and suggests that this biogenic phenethylamine can act as an environmental and physiological factor which may determine how the mollusc heart responds to dopamine. PMID- 2882925 TI - Species differences in lung mitochondrial monoamine oxidase activities. AB - Pulmonary mitochondrial monoamine oxidase (MAO) activity was examined in preparations from rat, rabbit and guinea-pig with 12 different amines as substrates: serotonin, norepinephrine, and octopamine (type A specific); tryptamine, benzylamine, 5-methoxytryptamine, 5-methyltryptamine, p methoxyphenylethylamine, and 3,4-dimethoxyphenethylamine (type B specific); and tyramine, dopamine and 3-methoxytyramine (type A + B specific). The oxidation of type A and type A + B substrates was greater in guinea-pig lung mitochondria than in rat or rabbit preparations. Except for benzylamine, the oxidation of type B substrates was similar in all three species. Benzylamine was not oxidized by guinea-pig lung mitochondria but was actively metabolized by rat and rabbit preparations. PMID- 2882926 TI - Rotifer neuropharmacology--III. Adrenergic drug effects on Brachionus plicatilis. AB - Norepinephrine (NE) induces three pharmacological effects in Brachionus plicatilis. As a result of excitation the rate of ciliary motion and swimming increases, and the animals flip their foot constantly at a rapid rate. This rapid foot flipping was used as a specific model to measure adrenergic effects in B. plicatilis. Phenylephrine induces the same effect at identical efficacy, while isoproterenol and salbutamol, two beta-agonists, show one-half and one-tenth NE efficacy. The beta blocker propranolol and the alpha blocker tolazoline both antagonize foot flipping induced by NE. However, propranolol shows antagonism because it causes foot paralysis by itself. Timolol, another beta blocker but without the membrane effect of propranolol, does not antagonize the alpha receptor mediated NE effect, nor does it cause foot paralysis. Propranolol, timolol and tolazoline also show agonist activity, inducing foot flipping. NE does not antagonize the foot paralysis induced by propranolol, only its anesthetic effect by delaying its onset. These results indicate that the foot flipping induced by NE is a receptor-mediated alpha adrenergic effect, while the foot paralysis is caused by membrane phenomena. PMID- 2882927 TI - Cholinergic control of the mechanical properties of the catch connective tissue in the holothurian body wall. AB - Effects of acetylcholine (ACh), ACh-agonists and antagonists were studied on the viscosity of the dermis of the sea cucumber Holothuria leucospilota. ACh and nicotinic agonists caused an early increase in viscosity and late decrease. Muscarinic agonists produced a viscosity decrease. The viscosity increase elicited by nicotine was inhibited by tubocurarine. The viscosity decrease caused by methacholine was suppressed by atropine. The mechanical properties of this connective tissue are very likely controlled by both nicotinic and muscarinic cholinoreceptors. PMID- 2882928 TI - Correlative studies on changes in lipid composition of gills and uptake of chemicals of willow shiner fish (Gnathopogon caerulescens) by exposure to detergent. AB - One group of willow shiner (Gnathopogon caerulescens) was exposed to 0.1 mg/l dodecylbenzenesulfonate (DBS) for analysis of lipid composition of gill extracts. Another group of fish was exposed to 0.0003 mg/l 2,4,6-trichlorophenyl-4' nitrophenyl-ether (CNP) after regular intervals of pre-exposure to 0.1 mg/l DBS for analysis of uptake of CNP. The whole body residues of CNP were characterized by a 60% drop in DBS pre-exposure for 14 and 21 days. The cholesterol/total phospholipid ratio increased to 0.22 and 0.28 after 14 and 21 days from the normal of 0.18. These biochemical results might be correlated with the changes observed by the uptake of CNP. PMID- 2882929 TI - Effects of inducer pretreatment on liver function and morphology in the mountain vole Microtus montanus. AB - Liver function and morphology of the mountain vole, Microtus montanus, were examined after i.p. injections of phenobarbital, beta-naphthoflavone, or Aroclor 1254 at three dose levels. The results of the liver function tests showed serum glutamic pyruvic transaminase and serum malathion carboxylesterase activities were normal in all the treatment groups. The histological results showed no necrotic tissue but did reveal two different morphological stages related to the level of monooxygenase activity; a low induction state was represented by foamy vacuolated hepatocytes while high induction states were related to enlarged, swollen, hypertrophied cells. PMID- 2882930 TI - Actions of deltamethrin and tralomethrin on cholinergic synaptic transmission in the central nervous system of the cockroach (Periplaneta americana). AB - Deltamethrin (RU 22974) and tralomethrin isomers (RU 24784 and RU 24785) block transmission at the cercal-afferent giant-interneuron synapses of the cockroach, when bath-applied to the desheathed ganglion at micromolar concentrations. The time-course of the events leading to the blockage suggests two possible target sites: one located presynaptically and the other situated on postsynaptic membranes. PMID- 2882931 TI - Effects of synthetic peptides on giant neurons identified in the ganglia of an African giant snail (Achatina fulica Ferussac)--II. AB - Thirteen synthetic biologically-active peptides, which were classified into the peptides proposed as neurotransmitters in mammals and invertebrates and neural venom peptides, were investigated for their effects on the following six identifiable giant neurons of an African giant snail (Achatina fulica Ferussac): RAPN (right anterior pallial neuron), INN (intestinal nerve neuron), RPeNLN (right pedal nerve large neuron), LPeNLN (left pedal nerve large neuron), d-LPeLN (dorsal-left pedal large neuron) and d-LPeCN (dorsal-left pedal constantly firing neuron). Oxytocin and proctolin at 10(-4)M excited the RAPN membrane potential, whereas FMRFamide at the same concentration inhibited the same neuron. FMRFamide at 10(-4)M markedly inhibited the d-LPeLN membrane potential, sometimes produced inhibition of RPeNLN and LPeNLN, showed varied effects (excitatory or inhibitory) on INN, and had no effect on d-LPeCN. The other peptides examined had almost no effect on any of the neurons tested. PMID- 2882932 TI - Changes of the liver UDP-glucuronosyltransferase activity in trout (Salmo gairdneri Rich.) acutely exposed to selected aquatic toxicants. AB - Rainbow trout were exposed for 4 or 8 days to various types of toxicants, each applied to the test water at a high sublethal concentration. The activity of liver UDP-glucuronosyltransferase (UDP-GT) was assayed from the submitochondrial fraction using p-nitrophenol as an aglycone. Activity of UDP-GT was inhibited by 2,4,6-trichlorophenol, pentachlorophenol and dehydroabietic acid, all toxicants regularly found in effluents of the pulp and paper industry. The heavy metals cadmium and zinc, the polychlorinated biphenyl, Pyralene 3010, and chloroform did not affect UDP-GT activity. The slimicide N-methyl-dithiocarbamate (Vapam) significantly increased the enzyme activity. PMID- 2882933 TI - Comparative studies on additive effects of sodium dodecylbenzensulfonate and sodium stearate on uptake of chemicals by willow shiner (Gnathopogon caerulescens). AB - Comparative studies between sodium dodecylbenzensulfonate (DBS) and sodium stearate (SNa) were performed on the additive effects of the uptake of chemicals in a fresh water fish, the willow shiner (Gnathopogon caerulescens), by the use of a continuous flow water system. The chemicals selected were 2,4,6 trichlorophenyl-4'-nitrophenyl ether (CNP) as a non-polar lipophilic substance and cadmium salt (Cd) as polar hydrophilic substance. DBS had no promotive and depressive effects on the uptake of Cd. SNa had no promotive and depressed effects on the uptake of CNP and Cd. PMID- 2882934 TI - Temperature sensitivity of cardiac muscarinic receptors in bat atria and ventricle. AB - In contrast to other mammals, muscarinic receptors in the bat ventricle can mediate significant decrease in basal contractile force (greater than 50%), not only at 37 degrees C but also at hibernation temperature (12 degrees C). At frequencies of contraction that approximate in vivo values for 37-12 degrees C, no significant shift in receptor affinity or maximum response to applied acetylcholine was found for either ventricular or atrial muscle. Low temperature does not appear to compromise receptor function in hibernators. The atypical cholinergic innervation of the ventricle may maintain a regulative role during hibernation. PMID- 2882935 TI - Comparison of the effects of FMRF-amide and pQDPFLRF-amide on identified Helix neurons. AB - Intracellular recordings were made from a selection of identified neurons in the sub-oesophageal ganglia of Helix aspersa, and their responses to the molluscan neuropeptides FMRF-amide and pQDPFLRF-amide compared. While FMRF-amide excited certain neurons and inhibited others, pQDPFLRF-amide did not produce excitation in any of the cells tested. A few cells were unresponsive to pQDPFLRF-amide, but most were inhibited with varying potency. FMRF-amide was generally 10-100 times more potent than pQDPFLRF-amide, but one cell, E13 in the visceral ganglion, showed equal sensitivity to the two peptides. On most cells there was no clear evidence for cross desensitization between the two peptides, although it is possible that in some cases where both peptides are inhibitory they may be acting on a single receptor. PMID- 2882936 TI - Effects of paraquat on mitochondria of rat skeletal muscle. AB - The effect of the herbicide paraquat (N,N'-dimethyl 4,4'-bipyridium), known to damage the lipid cellular membrane by peroxidation with superoxide radicals and a singlet oxygen, was investigated on skeletal muscle mitochondria. Minced rat gastrocnemius muscles were incubated in 8 mM paraquat solution. Mitochondrial fractions prepared from the incubated muscles were examined with respect to respiratory function and the enzyme activity of cytochrome c oxidase and succinate-cytochrome c reductase in the electron transport chain. The ADP/O ratio, RCR, and state 3 rates (= oxygen consumption in state 3) decreased gradually. State 4 rates (= oxygen consumption in state 4) increased in the initial stages and decreased after longer incubations. Enzyme activities gradually increased. These results suggested that paraquat damaged the mitochondrial membrane and disrupted oxidative phosphorylation in the early stage of incubation. Also, the electron transport chain was accelerated in the earlier stage and broken following a longer incubation. The inhibitory modality of paraquat on mitochondrial respiration was shown to be different from that of other known inhibitors. PMID- 2882937 TI - Activities and toxicological significance of hepatic microsomal enzymes of the kestrel (Falco tinnunculus) and sparrowhawk (Accipiter nisus). AB - Activities of hepatic microsomal monooxygenase and epoxide hydrolase in sparrowhawks and kestrels were determined using organochlorine substrates. Monooxygenase activities were low in the kestrel and very low in the sparrowhawk compared to those in the male rat, down to environmentally realistic substrate concentrations. Epoxide hydrolase activities were very low in both species. These activities are discussed in relation to feeding ecology and susceptibility to organochlorine pollutants. PMID- 2882938 TI - The influence of water pH on the perivitelline fluid of perch (Perca fluviatilis) eggs. AB - The diameter, trans-chorion potential difference and perivitelline-fluid pH of the eggs of perch (Perca fluviatilis) have been measured in a range of water pH (8-4.5). The water used was relatively nutrient rich. Eggs transferred from pH 8 to pH 4.5 shrink; probably as a result of loss of water from perivitelline fluid. Trans-chorion potential differences are close to zero over the range of pH. Mean perivitelline-fluid pH is higher than external water pH at pH 6.7 and above. Below pH 6.7, mean perivitelline-fluid pH is approximately the same as external water pH. The results suggest a non-Donnan distribution of hydrogen ions. The results are compared with data on salmonid eggs in nutrient-poor waters. PMID- 2882939 TI - Hyperphosphataemia in histamine injected laying hens. AB - The effects of histamine on soluble calcium concentrations in gastrointestinal tract contents, acid secretion, urinary phosphorus excretion, plasma free hydroxyproline and inorganic phosphorus levels were studied in laying hens during egg shell formation. Histamine induced hyperphosphataemia, hyperhydroxyprolinemia and decreased soluble gastrointestinal calcium at 3 hr after injection. Cimetidine inhibited all effects induced by histamine. This suggests that hyperphosphataemia arises from increased bone resorption provoked by decreased soluble intestinal calcium during egg shell formation. PMID- 2882940 TI - DNA repair synthesis in cultured fish and human cells exposed to fish S9 activated aromatic hydrocarbons. AB - Unscheduled DNA repair synthesis was measured autoradiographically in cultured rainbow trout gonad (RTG) and human fibroblast (HF) cells following exposure to aflatoxin B1 (AFB1), 3,4-benzopyrene (BP), 1,2,5,6-dibenzanthracene (DBA), 1,2 benzanthracene (BA) and pyrene (PY) activated with S9 prepared from rainbow trout liver. S9 from rainbow trout injected with Arochlor 1254 or an oil extract was compared with S9 from Fischer rats injected with Arochlor 1254 for the ability to activate AFB1 and cause DNA repair in RTG and HF cells. All three types of S9 activated AFB1, but the measured DNA repair response was greater in the HF cells. A significant grain count response was found following exposure of HF cells to fish S9-activated BP. Using assay conditions which enhance fish cell grain counts, a significant level of DNA repair was also found in RTG cells exposed to fish S9-activated BP. Marginal but statistically significant amounts of DNA repair were elicited in HF and RTG cells exposed to rainbow trout S9-activated BA and DBA, but no response was detected following PY exposure. Fish S9 was found to be able to activate a series of polycyclic aromatic hydrocarbons (PAH) and cause DNA repair synthesis in both fish and mammalian cells. The magnitude of the repair response roughly parallels the carcinogenic potential of the PAHs. These results elicit trans species and phyla comparisons which help to validate fish as models for aquatic carcinogenesis research, and also demonstrate PAH DNA-damaging effects on fish DNA, adding further credence for studying the effects of these chemicals on aquatic organisms. PMID- 2882941 TI - The effects of procaine, strychnine and penicillin on nociceptive neurons in leech segmental ganglia. AB - Procaine, strychnine and penicillin selectively depolarized the membrane potential and prolonged the action potential recorded in the lateral but not the medial nociceptive (N) cell in the hirudinid leech Macrobdella decora. In contrast, procaine did not differentiate between medial and lateral N cells in two other hirudinid leeches Hirudo medicinalis and Haemopis marmorata. In these species, the drug equally decreased the amplitude of action potentials in both types of N cells without effecting their resting membrane properties. In the nociceptive neurons of the glossiphoniid leech Haementeria ghilianii which possesses only one type of N cell, procaine produced a depolarization and prolonged the action potential. This finding indicates that the single pair of N cells in Haementeria is of the lateral type. The results suggest that the lateral type N cell in Macrobdella and Haementeria share a unique Na+-dependent conductance which is selectively opened by the local anesthetics procaine and strychnine as well as by penicillin. This conductance is either not present or insensitive to the drugs in the homologous N cells in the two other leech species examined. PMID- 2882943 TI - Effects of adenosine perfusion on the metabolism and contractile activity of Rana ridibunda heart. AB - The effects of adenosine were examined on the isolated perfused heart of the frog Rana ridibunda. Adenosine produced negative chronotropic and inotropic effects on frog ventricle in a concentration-dependent manner. The effects of adenosine on cardiac metabolism were also investigated by measuring the tissue content of adenine nucleotides, lactate, pyruvate, adenosine and inorganic phosphate, during adenosine perfusion. Adenosine had no effect on the tissue content of metabolites. No net synthesis of adenine nucleotides was observed during perfusion with increasing concentrations of adenosine. Lactate output from the heart decreased significantly with adenosine perfusion. Correlation of adenosine effects on cardiac muscle with the effects of hypoxia are discussed. PMID- 2882942 TI - Contractile and relaxant effects of jellyfish toxin on the vascular and intestinal tissues. AB - A toxic component (pCrTX) of jellyfish Carybdea rastonii (10(-8)-10(-6)g/ml) caused a contraction in both rat aorta and guinea-pig taenia coli which was partially inhibited by indomethacin or aspirin. pCrTX (10(-7)-10(-6)g/ml) relaxed the norepinephrine-induced contraction in rat aorta which was inhibited by removing endothelium or by adding methylene blue. These results suggest that a portion of the pCrTX-induced contraction is due to release of prostaglandin(s) and that the pCrTX-induced relaxation is due to release of an endothelium-derived relaxing factor. PMID- 2882944 TI - Frog retinal pigment screening and lithium. AB - The effect of the intraperitoneal injection of lithium on the pattern of the pigment screening (PS) of the frog retina has been studied in various illumination conditions. Lithium enhances the PS pattern induced by dark and it substantially modifies the PS pattern induced by the other light conditions. The dark-induced PS pattern is very stable and might be regulated by a single factor. The PS of light-adapted frogs is easily modified by drug administration and probably depends on a variety of factors which may be affected differently by the various injected substances. The possibility that lithium, melatonin and darkness might act in the same way or on the same system which regulates the PS in dark adaptation must not be disregarded. PMID- 2882945 TI - FMRFamide-like immunoreactivity and arylamidase activity in turbellarians and nemerteans--evidence for a novel neurovascular coordinating system in nemerteans. AB - The tetrapeptide Phe-Met-Arg-Phe-NH2 (FMRFamide) has been immunolocalized in the nervous systems of seven species of Turbellaria and four species of Nemertea. The 11 species represent all the major turbellarian and nemertean taxa, and illustrate most of the various life styles found in these animals. The FMRFamide like reactivity coincides with histochemically demonstrable arylamidase activity in the nervous systems. It is suggested that the FMRFamide-like reactivity demonstrates the presence in these lower invertebrates of one or more biologically active peptides, analogous to those of higher invertebrates and chordates and acting as putative neurotransmitters and coordinators of growth, maturation and muscular activities. The arylamidases occurring with the peptides are probably an integral part of these peptide-mediated control systems. The nemertean vascular system is especially rich in arylamidases and is believed to be concerned primarily with peptidergic control of bodily functions, rather than with transport of metabolites. PMID- 2882946 TI - Lymphoid tissue responses to perfluorocarbon emulsion in mice. AB - The effects of either intraperitoneal or intravenous injection of low doses (5 or 10 ml/kg) of the proprietary emulsified perfluorocarbon-based blood substitute, Fluosol-DA 20%, on mouse lymphoid tissue and antibody production against sheep erythrocytes (SRBC) have been investigated. Mean liver weight was significantly increased and gut mesenteric lymph node (MLN) weights decreased in all animals injected with Fluosol-DA, irrespective of route of administration. In contrast, spleen weight decreased following intravenous injection of emulsion at 5 ml/kg. The mean plasma haemagglutination response to SRBC was significantly (P less than 0.01) increased in animals injected intraperitoneally with Fluosol at both doses but was similar to control in all other cases. These results show that lymphoid tissue responses to Fluosol-DA in mice are variable and that antibody production against intraperitoneally-injected SRBC is enhanced by prior injection of emulsion into the peritoneal cavity. PMID- 2882947 TI - Descending and segmental spinal pathways differently regulate contractions of antagonistic muscles of frogs in vitro. AB - A comparison of fibres descending through the ventral column and segmental afferent fibres was carried out using an isolated frog spinal cord-nerve-muscle preparation with a pair of antagonistic muscles. The m. tibialis anterior (TIB) was contracted with stimulation of the ventral column much stronger than with that of the dorsal root (DR). Contraction of the m. gastrocnemius (GAS) was selectively induced with DR stimulation. These results suggest that the descending fibres and segmental afferent fibres preferentially regulate contractions of the flexor (the TIB) and the extensor (the GAS), respectively. Effects of alpha-aminoadipate, methysergide and LSD were also examined. PMID- 2882948 TI - The effect of copper on intact swine erythrocytes. AB - The effect of copper on intact swine erythrocytes was investigated in vitro. When treated with copper, a decrease in the GSH content, accumulation of copper in the cell, loss of potassium and gain of sodium, cross-linking of membrane proteins and echinocytic transformation were observed. All of these phenomena seem to be caused by a potent oxidant action of copper. These cytotoxic effects of copper were markedly inhibited by the addition of bovine serum albumin in the incubation medium. These results may help to understand the mechanism of hemolysis associated with copper poisoning in vivo. PMID- 2882949 TI - Studies on the influence of nitrite on methemoglobin formation in Amazonian fishes. AB - Twenty one species of fishes, collected from the Rio Solimoes and a tributary lake in the Amazon Basin near Manaus, showed a wide range of methemoglobin formation 1 hr after a dose of 30 mg/kg of sodium nitrite i.p. Methemoglobin formation in two experimental fishes, Brycon cf. melanopterum and Semaprochilodus insignis, maintained in tanks in our INPA laboratory, was studied in detail. Both fishes survived a dose of 10 mg/kg of nitrite i.p. but usually died within 3 hr of a dose of 30 mg/kg with levels of blood methemoglobin in excess of 80%. Methemoglobin produced in vitro by addition of nitrite to fresh blood was slowly reduced back to hemoglobin over a period of several hours at room temperature. Hemoglobin in hemolysates was auto-oxidized to methemoglobin at pH 6.1 and below but not at 6.9 and above. PMID- 2882950 TI - Components of increased labelling with putrescine and fucose during healing of skin wounds. AB - To study the glycoproteins and transglutaminase substrates involved in healing, wounds were made in the skin of anesthetized rats with a biopsy punch. Explants made 1-5 days later were incubated with [3H]-labelled putrescine, fucose or proline. As compared with unwounded skin there was an increased incorporation of label which was greatest at 3 days. Incubation for various times suggests that the incorporation of fucose and proline is dependent on protein synthesis, whereas putrescine is incorporated into preformed proteins. Putrescine and fucose label polypeptides with an Mr of about 45,000 before and 14,000 after reduction. These correspond in size with the aminopropeptide of type III collagen. Other labelled material of higher molecular weight is partly degraded to similar polypeptides on collagenase digestion. Much of the [3H]putrescine in the polypeptides is in the form of gamma-glutamyl putrescine. It is hypothesized that isopeptide linkage of the aminopropeptide III occurs in wound healing. PMID- 2882951 TI - Management of hypertension in chronic renal failure. PMID- 2882952 TI - Effect of antihypertensive agents on renal function. PMID- 2882953 TI - Localization and linkage of three polymorphic DNA sequences on human chromosome 20. AB - The D20S6 locus has been sublocalized by in situ hybridization using the pD3H12 probe to human chromosome band 20p12 and the D20S4 locus using the pMS1-27 probe to 20q13.2. A rare new restriction fragment length polymorphism detected in MspI digested DNA by the pMSI-27 probe is reported. Linkage studies in nine families have shown that the D20S6 locus is linked to D20S5 (formerly mapped to 20p12 by in situ hybridization) with a maximum likelihood estimate of 0.07 for the recombination frequency (lod score = 9.07) and a confidence interval of 0.02 to 0.14. Estimated recombination frequencies were similar in males and females. Using both two- and multipoint analyses, linkage of D20S4 with the D20S5 and D20S6 loci was excluded and the suggested order for the three loci on chromosome 20 is D20S5-D20S6-centromere-D20S4. D20S5 and D20S6 are very useful markers for linkage studies because of their close proximity and reasonably good polymorphic information content values. PMID- 2882954 TI - A mouse homeo box-containing gene maps near a developmental mutation. AB - Mouse genes containing homeo box domains are predicted to fulfill important functions in embryogenesis. Using recombinant inbred mouse strains, we have mapped a mouse gene which contains a homeo box with homology to the Drosophila engrailed gene. This gene maps to mouse chromosome 1 near or at the dominant hemimelia locus which is a known mouse developmental mutation. PMID- 2882955 TI - Genetic mapping of Prm-1, Igl-1, Smst, Mtv-6, Sod-1, and Ets-2 and localization of the Down syndrome region on mouse chromosome 16. AB - Molecular probes were used as markers in the backcross (Czech II X BALB/cPt) X Czech II to determine the positions of six genes on mouse chromosome 16 (MMU 16). The order of the genes mapped is (centromere), protamine-1 (Prm-1), immunoglobulin lambda 1 light chain (Igl-1), preprosomatostatin (Smst), an endogenous mouse mammary tumor virus locus (Mtv-6), and two more distal sequences, superoxide dismutase, cytoplasmic form (Sod-1), and the proto-oncogene sequence Ets-2. The largest recombination frequency between any two adjacent markers is 24 cM, and thus the position of any marker on MMU 16 that is polymorphic between these two strains can be readily determined in this backcross. A region of MMU 16 which corresponds to the Down syndrome region of human chromosome 21 is located near the distal end of the chromosome. PMID- 2882956 TI - Mapping polypeptide hormone genes in the mouse: somatostatin, glucagon, calcitonin, and parathyroid hormone. AB - Mouse-Chinese hamster hybrids segregating mouse chromosomes were analyzed by Southern hybridization techniques to map the genes for somatostatin (Smst), glucagon (Gcg), calcitonin (Calc), and parathyroid hormone (Pth). The mouse gene for somatostatin, detected on a 20-kb EcoRI fragment, is located on mouse chromosome 16. Glucagon cDNA hybridized to a 14-kb EcoRI fragment residing on chromosome 2. Calcitonin and parathyroid hormone genes, detected on 7.8-kb HindIII and 6.0-kb BamHI fragments, respectively, were on mouse chromosome 7. The calcitonin and parathyroid hormone genes appear to be part of a larger linkage group which has been conserved in mouse and man. PMID- 2882957 TI - Undetermined utility of almitrine. PMID- 2882958 TI - Adrenergic bronchodilators and potassium. PMID- 2882959 TI - Response to inhaled bronchodilators in COPD. PMID- 2882961 TI - [Combined multiple endocrine neoplasia (MEN I and MEN IIa)]. PMID- 2882962 TI - [Clinical uses of the saphenous neurovascular axial skin flap in treating skin defects of the lower extremity]. PMID- 2882960 TI - [Multiple endocrine neoplasia (MEN)--Wermer and Sipple syndrome]. AB - The illness-process of four patients, two with MEN I (Wermer syndrome) and two with MEN IIa (Sipple syndrome) is described and the therapeutical proceeding explained. The fundamental principle of therapy is the extirpation of hormone producing tumors, in the course of which MEN requires a special sequence in surgical proceeding. Although curative therapy was not possible in all cases, all four patients are still alive. The period of observance surveyed amounts from one year up to eleven years. The importance of family screening is shown in the fact that in two families more sick people were to be found. PMID- 2882963 TI - [Potentiation of the bronchodilating effect of beta-adrenergic agonists in guinea pigs with ketotifen]. PMID- 2882964 TI - Sports dentistry: a new role. PMID- 2882966 TI - Topical 5-aminosalicylic acid versus prednisolone in ulcerative proctosigmoiditis. A randomized, double-blind multicenter trial. Danish 5-ASA Group. AB - The therapeutic efficacy of a slightly acidic, buffered suspension of 1000 mg 5 aminosalicylic acid (Pentasa) was compared with that of 25 mg prednisolone following daily rectal administration to outpatients with mild to moderate proctosigmoiditis. The study was carried out as a randomized, double-blind trial in seven gastroenterological departments. A total of 123 patients were included of whom 114 completed the study (53 5-aminosalicylic acid, 61 prednisolone). The patient population was representative for the disease as it ordinarily appears in medical outpatient clinics. After 14 days, patients in total remission discontinued the treatment, while the rest were treated for another two-week period. Improvement or remission was seen in 77% of the 5-aminosalicylic acid treated patients and in 72% of the prednisolone-treated patients (P greater than 0.05). More than half the patients requiring prolonged treatment benefited from it, which points to an advantage of extended therapy. Side effects were few and mild. It is concluded that the applied suspension of 5-aminosalicylic acid is at least as efficient as prednisolone for topical treatment of patients with slightly to moderately active proctosigmoiditis. PMID- 2882965 TI - Inhibition of 5-lipoxygenase pathway of arachidonic acid metabolism in human neutrophils by sulfasalazine and 5-aminosalicylic acid. AB - The possible effect of sulfasalazine, 5-aminosalicylic acid, and acetyl-5 aminosalicylic acid on endogenous arachidonic acid release and metabolism was studied in human polymorphonuclear leukocytes (PMNs). A new in vitro assay was used by which [1-14C]arachidonic acid is incorporated by purified peripheral PMNs until steady state was obtained (5 hr). After preincubation with the test drugs prior to activation with calcium ionophore A23187, the released eicosanoids were isolated by extraction and thin-layer chromatography (TLC) and quantitated by autoradiography and laser densitometry. Median drug concentrations needed for 50% inhibition of leukotriene B4 and 5-hydroxyeicosatetraenoic acid (5-HETE) release was 4-5 mM (range 1-9 mM) for both sulfasalazine and 5-aminosalicylic acid. The acetylated derivative of 5-aminosalicylic acid was ineffective. The present data suggest that inhibition of arachidonic acid lipoxygenation may be an essential action of sulfasalazine and its active metabolite, 5-aminosalicylic acid. Interference with lipoxygenase enzymes, rather than a steroid-like inhibition of arachidonic acid release from intracellular phospholipids, seems to be the mode of action. PMID- 2882967 TI - Diabetes Control and Complications Trial (DCCT): results of feasibility study. The DCCT Research Group. AB - The Diabetes Control and Complications Trial (DCCT) is a multicenter, randomized, clinical study designed to determine whether an intensive treatment regimen directed at maintaining blood glucose concentrations as close to normal as possible will affect the appearance or progression of early vascular complications in patients with insulin-dependent diabetes mellitus (IDDM). We present the baseline characteristics and 1-yr results of the initial cohort of 278 subjects randomized in phase II of the trial, a phase designed to answer several feasibility questions before initiating a full-scale trial. During phase II, recruitment was completed on schedule. The 191 adults and 87 adolescents were randomized either to standard treatment (90 adults and 42 adolescents), designed to approximate conventional diabetes treatment, or to experimental treatment (101 adults and 45 adolescents), designed to achieve near-normal blood glucose and HbA1c concentrations. With few exceptions, baseline demographic, ophthalmologic, renal, and other medical characteristics were evenly distributed by randomization between the two treatment groups in both age strata. Glycemic control at baseline, as assessed by HbA1c concentrations and by blood glucose profiles, was comparable between the treatment groups in both age strata. The treatment strategies employed produced statistically significant and clinically meaningful differences in HbA1c concentrations and blood glucose profiles between the experimental- and standard-group subjects for both adults and adolescents. These differences were maintained throughout the feasibility phase. Except for an increased incidence of hypoglycemia in the experimental group, the two treatment regimens maintained or improved the clinical well-being of subjects in both groups. Adherence and completeness of follow-up were excellent (greater than 95%), and the methods employed to measure biochemical and pathologic characteristics of IDDM proved to be reliable, reproducible, and precise. The feasibility phase of the DCCT demonstrated that a complex multicenter, randomized study of the relationship between diabetes control and complications can be performed. The full-scale, long-term trial therefore has been initiated. PMID- 2882968 TI - [Differences in the temporal intervals of the effect of mediators on nerve cells as a method of information coding]. PMID- 2882969 TI - Relationship between sulfotransferase activity and susceptibility to acetaminophen-induced liver necrosis in the hamster. AB - The effect of pretreatments which modulate acetaminophen sulfotransferase activity on the hepatotoxicity of acetaminophen have been examined in the hamster. Co-administration of sodium sulfate modestly enhanced the formation of acetaminophen sulfate, but provided little protection against liver injury. In isolated hepatocyte studies, sodium sulfate enhanced the Vmax of acetaminophen sulfotransferase activity, but did not alter the apparent Km toward acetaminophen. Administration of 2,6-dichloro-4-nitrophenol with acetaminophen selectively depressed acetaminophen sulfate formation in vivo and significantly exacerbated acetaminophen hepatotoxicity. In kinetic studies using isolated hamster hepatocytes, 2,6-dichloro-4-nitrophenol competitively inhibited acetaminophen sulfotransferase with a Ki of 2.5 X 10(-6) M. The data indicate that in the hamster, acetaminophen sulfotransferase activity plays a relatively minor role in the modulation of acetaminophen hepatotoxicity, and that, at hepatotoxic doses, the capacity limitation on this enzyme system is determined to a greater extent by its Km (app) value than by limitation in cofactor (3' phosphoadenosine 5'-phosphosulfate) availability. PMID- 2882970 TI - Dose-dependent pharmacokinetics of ibuprofen in the rat. AB - The linearity of the pharmacokinetics of ibuprofen was examined in male Sprague Dawley rats given iv bolus doses of 10, 20, and 50 mg/kg ibuprofen. Plasma and urine concentrations of ibuprofen and its two major metabolites, OH-ibuprofen and COOH-ibuprofen, were determined by HPLC and the binding of ibuprofen to plasma proteins was measured by an ultrafiltration technique. The systemic plasma clearance (CLtot) of ibuprofen was dose-dependent and decreased from 0.29 to 0.14 liter/hr/kg primarily as a result of a 65% decrease in the partial metabolic clearance to OH-ibuprofen while the average mean residence time (MRTtot) increased approximately 35% over the 10-50 mg/kg dosage range. Since there were no dose-dependent changes in the apparent steady state volume of distribution (Vss,tot), the mean harmonic half-life increased from 1.7-2.8 hr over the dosage range studied. The binding of ibuprofen to plasma proteins was relatively independent of concentration up to 90 mg/liter (mean free fraction approximately 5.5%), but became markedly concentration-dependent thereafter (free fraction up to 25.4% at 411 mg/liter). The mean recovery of total ibuprofen in the urine over 24 hours at 10 mg/kg was 62.1% and decreased by 24% and 40% at 50 and 20 mg/kg, respectively. This dose-dependent decrease in the percentage excreted in the urine was primarily due to a reduction in the recovery of OH-ibuprofen slightly offset by a small, but significant, increase in the urinary excretion of COOH ibuprofen between 10 and 50 mg/kg. The apparent pharmacokinetic parameters based on free, unbound concentrations of ibuprofen were also dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882971 TI - Nonenzymatic bioreduction in rat liver and kidney of nitroxyl spin labels, potential contrast agents in magnetic resonance imaging. AB - Paramagnetic nitroxyl spin labels have potential clinical utility as contrast agents in proton magnetic resonance imaging. Reduction of the nitroxyl moiety in vivo results in the formation of the diamagnetic hydroxylamine, which lacks contrast-enhancing activity. Bioreduction is therefore an important determinant of the imaging behavior of these agents. Both enzymatic and nonenzymatic reduction mechanisms have been suggested for nitroxyl spin labels. This study examines the nonenzymatic mechanisms in rat liver and kidney, mammalian tissues that demonstrate high reducing activity. Protein-free preparations, obtained by heat precipitation or ultrafiltration of rat liver and kidney homogenates, were used to test piperidine and pyrrolidine nitroxyl spin-label derivatives, for which imaging properties and bioreduction had previously been examined. For the piperidine derivative, the initial reduction rates in ultrafiltrates and supernatant fluids were 25-60% of those in whole liver and kidney homogenates. However, the pyrrolidine derivative was reduced at rates much slower than those in whole tissue homogenates. The reduction in whole tissue homogenates was NADPH dependent, while reduction in ultrafiltrates was unaffected by the addition of NADPH. Preincubation of the ultrafiltrates and supernatant fluids with ascorbic acid oxidase caused almost complete inhibition of the reduction. The reduction rates of these nitroxyl derivatives were determined in ascorbic acid solution; second order rate constants were 0.45 +/- 0.04 and 0.0042 +/- 0.001 mM-1 min-1 for the piperidine and pyrrolidine derivatives, respectively. The concentrations of ascorbic acid in the supernatant fluids and ultrafiltrates of rat liver and kidney were then predicted from the observed reduction rates and found to be virtually identical with those from spectrophotometric determinations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882972 TI - In vitro microsomal metabolism of the leukotriene receptor antagonist, 5-(2 dodecylphenyl)-4,6-dithianonanedioic acid (SK&F 102,081). AB - In vivo experiments indicate that the major route of metabolism of SK&F 102,081 [5-(2-dodecylphenyl)-4,6-dithianonanedioic acid] is via omega-oxidation and subsequent beta-oxidation. Therefore, in vitro experiments were designed to characterize the initial reaction of this pathway, omega-hydroxylation. SK&F 102,081 was metabolized by rat hepatic microsomes to two products; mass spectral analysis indicated that these products were the omega (omega) and omega minus one (omega-1) hydroxylated metabolites, 5-[2-(12-hydroxy)dodecylphenyl]-4,6 dithianonanedioic acid and 5-[2-(11-hydroxy)dodecylphenyl]-4,6-dithianonanedioic acid, respectively. NADPH and oxygen were required for the formation of these metabolites. Kinetic analysis of omega- and (omega-1)-hydroxylations of SK&F 102,081 indicated that the apparent Km for (omega-1)-hydroxylation (52.6 microM) was approximately 2.5-fold higher than the apparent Km for omega-hydroxylation (22.0 microM). Furthermore, the cytochrome P-450 inhibitor, metyrapone, produced differential inhibition of omega- and (omega-1)-hydroxylation. In addition, the terminal acetylenic analogue of SK&F 102,081, SK&F 103,600 (5-[2-(11 dodecynyl)phenyl]-4,6-dithianonanedioic acid), produced differential suicide inactivation of SK&F 102,081 omega- and (omega-1)-hydroxylations. These studies indicate that the omega- and (omega-1)-hydroxylations of SK&F 102,081 are probably carried out by different isozymes of hepatic cytochrome P-450 in the rat. Furthermore, the isozymes that hydroxylate SK&F 102,081 at the omega- and (omega-1)-positions may be similar to those which mediate similar reactions on endogenous compounds such as prostaglandins and leukotrienes. PMID- 2882973 TI - In vivo metabolism of the leukotriene receptor antagonist, 5-(2-dodecylphenyl) 4,6-dithianonanedioic acid (SK&F 102,081) in the guinea pig. AB - Both leukotrienes and their receptor antagonists possess substantial pharmacologic activity in in vitro systems, but their duration of action in vivo is extremely short. The exact mechanism of rapid inactivation of these lipids is unknown, but is likely due to metabolism. Therefore, the metabolic fate of a model antagonist 5-(2-dodecylphenyl)-4,6-dithianonanedioic acid (SK&F 102,081) was elucidated in anesthetized guinea pigs. Following iv administration of [14C]SK&F 102,081 (5 mg/kg), 85% of injected radioactivity was excreted in bile in 1 hr. Approximately 6% of the radioactivity in bile was associated with parent. At least 14 metabolites were present in bile, 2 of which accounted for almost 60% of the excreted radioactivity. Identification of biliary metabolites revealed that metabolism occurred by two major routes, omega-oxidation with subsequent beta-oxidation and acyl glucuronidation at approximately a 4:1 ratio. Since current structure-activity relationships suggest that omega-oxidation results in the loss of pharmacologic activity of SK&F 102,081, the rapid loss in pharmacologic activity observed in vivo may be due to rapid metabolism. PMID- 2882974 TI - Alterations in biliary excretory function by streptozotocin-induced diabetes. AB - Hepatic clearance and biliary excretion of model substrates for each of four carrier-mediated transport systems were studied in male Sprague-Dawley rats treated 28 days earlier with 45 mg/kg streptozotocin iv to induce uncontrolled insulin-deficient diabetes. Diabetic rats exhibited hyperglycemia (560 mg/dl), polyuria (160 ml/24 hr), polyphagia, polydipsia, and generalized myopathy. The plasma disappearance, biliary excretion, and elimination half-life of the anionic dye phenol red was unchanged in diabetic rats, but total clearance of phenol red was increased. Conjugation of phenol red with glucuronic acid appeared to be increased in diabetic rats, whereas acetylation of procainamide ethobromide was decreased. Plasma elimination and total clearance of cationic procainamide ethobromide, uncharged ouabain, and the bile acid taurocholate were significantly increased in diabetic animals. Biliary excretion of these three compounds was only slightly elevated in the first 15 min after administration and was decreased after 1 hr. Biliary and total systemic clearance were also increased from 2-3 fold for procainamide ethobromide, ouabain, and taurocholate. These changes in clearance are predominantly due to the 2-5-fold increase in steady state volume of distribution. Basal bile flow rates were increased by 62% after the induction of diabetes to 88 microliter/min/kg. Diabetic rats secreted higher levels of bile acids, cholesterol, and phospholipids into bile. These data indicate that long term insulin-dependent diabetes does alter hepatic excretory function. PMID- 2882975 TI - Uptake, metabolism, and secretion of 3'-methyl-N,N-dimethyl-4-aminoazobenzene by isolated perfused rat liver. AB - Uptake, metabolism, and biliary secretion of 3'-methyl-N,N-dimethyl-4 aminoazobenzene (3'-Me-DAB) were studied in isolated rat liver which was perfused with protein-free fluorocarbon medium. [14C]3'-Me-DAB (5-10 nmol) was injected into the portal vein and allowed to recirculate. The recovery of radioactivity in bile was 7.5, 14, and 20% at 15, 30, and 45 min of injection, respectively. At 45 min, the liver contained an additional 17% of injected radioactivity. Azo dye metabolites in perfused liver differed from those in vivo; metabolites co migrating with 3'-CHO-DAB and 3'-methyl-n,n-methyl aminoazobenzene (Me-MAB) (and the parent compound 3'-Me-DAB) were present, while metabolites co-migrating with 3'-Me-4'-OH-AB and 3'-CH2OH-MAB were increased and metabolites co-migrating with 3'-CH2OH-DAB were decreased. In bile from perfused liver, metabolites co migrating with 3'-CHO-DAB and 3'-Me-MAB were undetectable. When proteins from normal rat bile were injected into portal vein 15 min after the administration of 3'-Me-DAB, the compounds co-migrating with 3'-Me-MAB, 3'-CHO-DAB, 3'-Me-4'-OH-AB, and 3'-CH2OH-MAB decreased, and compounds co-migrating with 3'-CH2OH-DAB increased in the liver; in bile, there was increase in 3'-Me-MAB, 3'-CHO-DAB, and 3'-Me-4'-OH-MAB, which there was a decrease in N-Ac-3'-Me-4'-OH-AB and 3'-COOH DAB. Appearance of protein-metabolite adducts in bile was also observed after addition of normal bile proteins to the perfusate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882976 TI - Uptake and disposition of putrescine, spermidine, and spermine by rabbit lungs. AB - The pulmonary uptake and accumulation of the three polyamines in intact, ventilated, and perfused rabbit lungs was investigated. Lungs were perfused using Krebs-Ringer bicarbonate buffer with albumin in which putrescine, spermidine, or spermine were included at an initial concentration of 10(-3), 10(-2), 10(-1), 5, 10, or 20 mM. At a 5 mM concentration of spermidine and spermine, the uptake by isolated lungs reached a steady state equilibrium in 20-30 min of perfusion. This did not occur for putrescine, which showed linear uptake throughout the entire period of the 60-min perfusion. The lung uptake of putrescine for all perfusate concentrations was greater than that of spermidine or spermine, but all three showed concentration-dependent linear uptake. In the presence of harmaline (1 mM) and ouabain (1 mM), isolated perfused rabbit lungs showed a decrease in uptake of putrescine although no effect was seen for spermidine and spermine. Perfusate containing decreased sodium showed no effect on putrescine uptake by isolated rabbit lungs, but there was a significant increase in the uptake of spermidine and spermine. Significant uptake of all three polyamines was also observed when incubated separately with rabbit lung slices for 60 min. HPLC analysis of lung, the perfusate samples, lung slices, and the incubation medium after a 60-min incubation did not indicate the presence of metabolites of these polyamines. Likewise, the analysis of the lung homogenate incubated with polyamines did not show any metabolites confirming the absence of detectable pulmonary metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882978 TI - Conversion of N,N-dimethylaniline to N,N-dimethylaniline-N-oxide by a cytosolic flavin-containing enzyme from Trypanosoma cruzi. AB - A cytosolic NADPH-dependent FAD-containing enzyme purified from Trypanosoma cruzi epimastigotes [Kuwahara, White, and Agosin: Biochem. Biophys. Res. Commun. 124, 121 (1984); Arch. Biochem. Biophys. 239, 18 (1985)] catalyzes the conversion of N,N-dimethylaniline to its corresponding N-oxide. The identity of the product has been established by high performance liquid chromatography and paper chromatography elution patterns and by electron impact spectrometry. The oxidation of N,N-dimethylaniline was determined by following the oxidation of NADPH spectrophotometrically, and a double reciprocal plot of reaction velocity vs. substrate concentration was prepared. At an optimum pH of 8.0, the plot resulted in Km and Vmax values of 56 microM and 114 nmol X min-1 X mg of protein 1, respectively. The oxidative activity of the enzyme suggests that it may be involved in detoxication processes which may contribute to the resistance of T. cruzi to known antiprotozoal drugs. PMID- 2882977 TI - Conversion of melphalan to 4-(glutathionyl)phenylalanine. A novel mechanism for conjugation by glutathione-S-transferases. AB - One of the conjugates of melphalan, characterized following incubation with glutathione (GSH) and immobilized microsomal glutathione-S-transferases, has been identified as 4-(glutathionyl)-phenylalanine. This conjugate is formed by displacement of the mustard moiety. The structure was confirmed by reaction of the corresponding 4-halophenylalanines with GSH as well as by TLC, HPLC, and FAB mass spectrometry. Evidence is presented here to support the hypothesis that this novel reaction occurs via a cyclic aziridinium ion. To test this proposed mechanism, N,N-dimethyl-p-toluidine and its corresponding quaternary ammonium iodide salt were incubated with GSH in the presence of immobilized glutathione-S transferases at 37 degrees C for 1 hr at pH 7.4. The tertiary amine did not react, whereas the quaternary compound produced 4-(glutathionyl)toluene. The effect of ring substituent requirements for the reaction was evaluated. The formation of GSH adducts of alkylating agents may be a factor in the development of resistance to these drugs. PMID- 2882980 TI - The pharmacokinetics of all-trans-retinoic acid and N-(2-hydroxyethyl)retinamide in mice as determined with a sensitive and convenient procedure. Solid-phase extraction and reverse-phase high performance liquid chromatography. AB - An improved method for the analysis of retinoids in mouse plasma allows quantification of all-trans-retinoic acid (RA) and N-(2-hydroxyethyl)retinamide (NHERA) in amounts as low as 2 ng/ml (7 X 10(-9) M), the approximate endogenous concentration of RA. The procedure, involving solid-phase extraction and reverse phase HPLC, can be used for rapid processing of large numbers of samples. With this procedure, we have determined the terminal half-life for RA (0.5 hr) and have confirmed the half-life for NHERA (3.6 hr) in the plasma of mice dosed orally. We have also noted that the serum content of retinol is temporarily reduced following dosing with RA, but not with NHERA. PMID- 2882979 TI - Pharmacokinetic interaction between theophylline and chloramphenicol in rats. AB - The effects of chloramphenicol, a potent enzyme inhibitor, on the pharmacokinetics of theophylline were investigated in Sprague-Dawley rats. Chloramphenicol treatment, 75 mg/day intravenously for 3 days, significantly (p less than 0.05) decreased the plasma clearance of theophylline by 31% with no apparent effects on the volume of distribution (0.97 liter/kg). The elimination half-life in chloramphenicol treated rats (N = 6) was 4.8 hr, significantly (p less than 0.05) longer than the corresponding half-life, 3.4 hr, in control rats (N = 6). It appears that chloramphenicol has a marked inhibitory effect on the activity of the cytochrome P-450-dependent mixed function oxidase liver microsome system responsible for the oxidation and demethylation of theophylline. PMID- 2882981 TI - Urinary excretion kinetics of famotidine in rats. AB - Famotidine is a new histamine H2-receptor antagonist which has been demonstrated to be more potent than cimetidine and ranitidine in inhibiting gastric acid secretion. Nine groups of adult male Sprague-Dawley rats received an ia injection of various loading doses of famotidine followed immediately by a constant infusion of the drug at different rates for 6 hr. When steady state famotidine concentrations in plasma were low, renal clearance of the drug (CLR) was greater than glomerular filtration (GFR), and the ratio CLR/GFR was about 4.5 at plasma concentrations of 0.2-1.8 micrograms/ml, suggesting that famotidine was actively secreted by the renal tubules. The CLR decreased as famotidine concentration in plasma increased, and the ratio CLR/GFR approached 1 in the concentration range of 25-76 micrograms/ml, thus providing evidence for saturation of the secretory mechanism. The maximum rate of secretory transport (Tm) of famotidine averaged 180 micrograms/min/kg. On average, some 50-70% of an ia bolus dose was excreted in the urine as unchanged drug within 24 hr of administration. Over the dose range of 0.3-30 mg/kg famotidine, there was no dose-dependent effect on total or renal clearance. Since the lowest dose level, 0.3 mg/kg, is below the recommended human therapeutic dose for famotidine (0.6 mg/kg), the saturation of the renal excretion process observed here in rats is not likely to be of clinical significance. PMID- 2882982 TI - In vivo and in vitro biotransformation of theobromine by phenobarbital- and 3 methylcholanthrene-inducible cytochrome P-450 monooxygenases in rat liver. Role of thiol compounds. AB - A new in vitro method was developed and applied to establish the role of the hepatic cytochrome P-450 monooxygenases in theobromine biotransformation by control and phenobarbital (PB)- and 3-methylcholanthrene (3MC)-induced Sprague Dawley rats. In vivo theobromine metabolite formation and pharmacokinetic parameters were also determined to serve as a comparison for in vitro studies. In vivo, the major urinary metabolite was 6-amino-5-[N-methylformylamino]-1 methyluracil (3,7DAU) with lesser amounts of 3,7-dimethyluric acid (3,7DMU), 3 methylxanthine, 7-methylxanthine, 7-methyluric acid, and traces of dimethylallantoin (DMA). Following induction with 3MC, but not PB, selective increases occurred in the urinary excretion of 3,7DAU, indicating that a 3MC inducible cytochrome P-450 isozyme plays a significant role in this metabolic pathway. Both PB and 3MC induction increased slightly urinary elimination of DMA, a minor metabolite. Pharmacokinetic studies after a single oral dose of 5 mg/kg theobromine revealed a marked effect of 3MC treatment on theobromine elimination, as evidenced by a 59% decrease in theobromine t1/2, a 75% decrease in AUC, and a 284% increase in clearance. By contrast, PB had no effect. Fecal 14C elimination accounted for approximately 5% of the administered theobromine dose, and biliary excretion studies revealed the presence of 3,7DMU, DMA, 3,7DAU, and unchanged theobromine. Studies in vitro indicated that 3,7DMU was the major theobromine metabolite produced by liver microsomes. Conversion rates in PB- and 3MC-induced rats were 2- and 11-fold higher, respectively, than in controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882983 TI - Effects of aging on the properties of rhesus monkey liver microsomal NADPH cytochrome c (P-450) reductase. AB - Significant declines occur in several in vitro indices of the liver microsomal cytochromes P-450-dependent drug-metabolizing system during aging in inbred male rats. However, several investigators have expressed serious reservations concerning the extrapolation of data derived from rodent models to humans. The few studies to evaluate the hepatic P-450-dependent drug-metabolizing system in young and old primates found no age-related declines in in vitro indices. The present study was designed to characterize the important hepatic microsomal drug metabolizing enzyme, NADPH-cytochrome c (P-450) reductase (EC 1.6.2.4), as a function of aging in the rhesus monkey (Macaque mulatta). While certain properties of the solubilized and enriched enzyme remained relatively unchanged (molecular weight, kinetic profile, immunoprecipitatability), others exhibited marked shifts (specific activity, thermostability) as a function of aging. These changes contrasted with age-related alterations described in NADPH-cytochrome c (P-450) reductase isolated from inbred male rats. The present data suggest that inbred rodents may not accurately reflect possible age-dependent alterations in liver Phase I drug metabolism in primates. PMID- 2882984 TI - Extraction of omega- and omega-1-hydroxylauric acids with ethyl acetate results in formation of acetoxy products. AB - In studies of the regiospecific metabolism of lauric acid by monooxygenase enzymes, incubation medium from the reaction of [14C] lauric acid and microsomes is routinely acidified and extracted with ethyl ether. Separation of products by HPLC shows the formation of omega(12)- and omega-1(11)-hydroxylauric acids by rat liver microsomes. In a comparison of several extraction solvents, we observed that the extraction of incubation media with ethyl acetate alone was associated with the appearance of a major new metabolite peak concomitant with loss of the 12- and 11-hydroxylaurate peaks by 62 and 23%, respectively. No difference was observed between extraction procedures in the per cent recovery of radiolabel. Similar results were observed with extraction of lauric acid metabolites formed by fish liver microsomes. Acidification of the incubation media prior to ethyl acetate extraction prevented formation of the new metabolite peak. In experiments to identify the new metabolite(s), 11- and 12-hydroxylaurate products formed by rat liver microsomes were acetylated and found to show an HPLC retention time similar to that of the unknown metabolite peak formed with ethyl acetate extraction. Mass spectrometric analysis further showed that the methyl esters of 11- and 12-acetoxylauric acids were very similar to that of the methyl ester derivative of the unknown metabolite fraction. Thus, data indicate that the acetoxy derivatives of 11- and 12-hydroxylauric acids were formed by direct reaction of ethyl acetate with the laurate products formed by microsomal monooxygenase enzymes. This extraction procedure can produce a major shift in the amount and ratio of omega- and omega-1-hydroxylaurates measured in the incubation media. PMID- 2882985 TI - Biotransformation of caffeine, paraxanthine, theophylline, and theobromine by polycyclic aromatic hydrocarbon-inducible cytochrome(s) P-450 in human liver microsomes. AB - The microsomal metabolism of caffeine and its primary dimethylxanthine metabolites, paraxanthine, theophylline, and theobromine, was investigated in 15 different human livers, including those from two known nonsmokers and one known smoker. At least two distinct enzymes with differing substrate affinities have the potential to catalyze most methylxanthine N-demethylations and C8 hydroxylations in vitro; however, at the low methylxanthine concentrations routinely encountered in vivo, participation by the high affinity site is expected to predominate. It appears that the high affinity enzyme is a polycyclic aromatic hydrocarbon-inducible isozyme of cytochrome P-450, based on competitive inhibition by 7-ethoxyresorufin and benzo[a]pyrene, and based on a significant (p less than 0.001) correlation between 7-ethoxyresorufin-O-deethylation and methylxanthine demethylation rates. alpha-Naphthoflavone inhibited all methylxanthine demethylations in excess of 80% in two high activity livers, whereas 8-hydroxylations were generally inhibited less. Kinetic analysis of paraxanthine 7-demethylation in four different liver preparations resulted in similar Km values of 1.2 +/- 0.5 mM (mean +/- SD), whereas Vmax values varied 8 fold, compatible with participation by the same high affinity isozyme. Notable was the high degree of inter-liver variation in metabolic rates, with the known smoker showing the second highest activity among a 20-fold range in paraxanthine demethylation rates, consistent with polycyclic aromatic hydrocarbon-related enzyme induction. Maximal inhibition of paraxanthine 8-hydroxylation by alpha naphthoflavone left similar residual activities in the 15 liver preparations, indicating the presence of an enzyme activity that was not inducible. Furthermore, in low activity livers, more than 80% of paraxanthine 8 hydroxylation was mediated by an isozyme of cytochrome P-450 insensitive to inhibition by alpha-naphthoflavone. Our in vitro data show that the proportion of demethylation relative to hydroxylation products of paraxanthine correlate with 7 ethoxyresorufin O-deethylation rates. Taken together, the data provide a rationale for a potential in vivo marker of polycyclic aromatic hydrocarbon inducible cytochrome P-450 activity based on a urinary metabolite ratio of paraxanthine 7-demethylation to 8-hydroxylation products after caffeine intake. PMID- 2882986 TI - Pharmacokinetics of tetrabenazine and its major metabolite in man and rat. Bioavailability and dose dependency studies. AB - The pharmacokinetics of tetrabenazine (TBZ), a catecholamine and serotonin depletor, and its major metabolite, dihydrotetrabenazine (HTBZ), were studied in four patients affected by tardive dyskinesia, who were under treatment with different doses of TBZ (12.5-37.5 mg, t.i.d.), and in the rat. In the patients, the steady-state area under the plasma concentration-time curves (AUCs) of the metabolite were 82.6-199-fold higher than those of TBZ. The drug showed a small and erratic bioavailability (F = 0.06 +/- 0.026, mean +/- SD). It appears to be extensively metabolized, as no unchanged TBZ could be detected in the urine of the patients. Single oral doses of 0.5-10 mg/kg and single iv dose of 1 mg/kg of TBZ were each administered to four to six rats. The clearance of the drug following iv administration to the rat (mean +/- SD, 58.9 +/- 6.01 ml X min-1 X kg-1) was very close to the rat hepatic blood flow indicating a perfusion-limited clearance. An F value of 0.17 was obtained following iv and po doses of 1 mg/kg TBZ in the rat. The oral absorption of TBZ seems to be rapid and almost complete. Plots of the AUCs of TBZ and HTBZ vs. five different po doses (0.5-10 mg/kg) were linear with correlation coefficients of 0.998 and 0.986 for TBZ and HTBZ, respectively, suggesting linear kinetics in the examined dosage range. In both the patients and rats, the plasma profile of TBZ followed characteristics of a multiexponential pharmacokinetic model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2882987 TI - Flavin-containing monooxygenase activity in human liver microsomes. AB - Human liver microsomal flavin-containing monooxygenase activity has been studied using dimethylaniline N-oxidation and thiobenzamide S-oxidation. Except for one subject, the capacity of human liver microsomes to mediate these reactions were markedly increased at pH 8.4 compared to pH 7.4. The mean dimethylaniline N oxidase activities at pH 7.4 and 8.4 in the four subjects tested were 2.49 +/- 1.13 and 6.59 +/- 4.04 nmol mg-1 min-1, respectively (mean +/- SD, N = 4). The mean thiobenzamide S-oxidase activities at pH 7.4 and 8.4 were 1.39 +/- 0.51 and 2.74 +/- 1.28 nmol mg-1 min-1, respectively. At pH 7.4, an antibody to the human liver NADPH-cytochrome P-450 reductase inhibited dimethylaniline N-oxidation between 4 and 38%. The same antibody had no effect on this reaction at pH 8.4. Except for one subject, a battery of cytochrome P-450 inhibitors also had little effect on this reaction. Further, preincubating human microsomes at 45 degrees C in the absence of NADPH for 4 min destroyed approximately 90% of the dimethylaniline N-oxidase activity. These data collectively suggested that the flavin-containing mono-oxygenase is the major enzyme mediating this reaction in human liver microsomes. In contrast to dimethylaniline N-oxidation, thiobenzamide S-oxidation was significantly inhibited by the anti-reductase at both pH 7.4 and 8.4, respectively. These data indicate that cytochromes P-450 contribute significantly to this reaction in human liver microsomes. PMID- 2882988 TI - Metabolism of ethyl 2-(4-chlorophenyl)-5-(2-furyl)-oxazole-4-acetate, a new hypolipidemic agent, in the rat, rabbit, and dog. Glucuronidation of carboxyl group and cleavage of furan ring. AB - Metabolism of ethyl 2-(4-chlorophenyl)-5-(2-furyl)-oxazole-4-acetate (TA-1801), a new hypolipidemic agent, was studied in the rat, rabbit, and dog. Animals were given a single oral dose of 50 mg/kg TA-1801 labeled with 14C. The first metabolic reaction for TA-1801 was hydrolysis of the ester linkage. The resulting metabolite M1 was found to undergo further biotransformations, i.e. glucuronidation at the carboxyl group and ring cleavage of the furan group. These metabolic pathways were observed in all the species examined, although species differences were seen in the amount of metabolites. PMID- 2882989 TI - Mitotane (1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane) metabolism in perfusion studies with dog adrenal glands. PMID- 2882990 TI - Comparison of hepatic and renal metabolism of acetaminophen in male and female miniature swine. PMID- 2882991 TI - In vivo inhibition of phenacetin oxidation by suicide substrate 1 aminobenzotriazole. PMID- 2882992 TI - Pharmacogenetic association between the formation of 4-hydroxymephenytoin and a new metabolite of S-mephenytoin in man. PMID- 2882993 TI - Esmolol: a novel cardioselective, titratable, intravenous beta-blocker with ultrashort half-life. AB - Esmolol is an ultrashort-acting, cardioselective, intravenous beta-blocker with an elimination half-life of about nine minutes. After administration of a loading dose, its full therapeutic effect is evident within five minutes. Its efficacy in treating supraventricular arrhythmias is equal to that of propranolol, but unlike propranolol, the action of esmolol is titratable and is largely reversed within 10 to 30 minutes after stopping its administration. Esmolol is also effective in attenuating life-threatening perioperative tachycardia and hypertension caused by adrenergic stimulation in high-risk patients. PMID- 2882994 TI - [Legal questions in connection with HIV infection and AIDS]. PMID- 2882995 TI - [Various splinting technics and their indications for surgical dental preservation]. PMID- 2882996 TI - Insulin-related changes in the subcellular distribution of insulin receptors in intact rat liver: effects of acute hypoinsulinemia induced by diazoxide, somatostatin, and xylazine. AB - The effects of inhibitors of insulin secretion on the concentration of plasma insulin and on the subcellular distribution of hepatic insulin receptors have been examined in rats. Liver plasma membranes, Golgi fractions, and a total particulate fraction were prepared various times after the injection of diazoxide (10 mg), xylazine (0.5 mg), and somatostatin (20 micrograms as a bolus followed by a 20 micrograms/15-min infusion), solubilized by Triton X-100, and examined for specific insulin binding. Injection of each of these drugs caused a 4- to 8 fold decrease in plasma insulin concentration, and concomitantly, a 25-35% decrease in insulin binding to Golgi fractions; a 10% increase in insulin binding to plasma membranes also occurred in diazoxide-treated rats. Insulin binding to the total particulate fraction was unaffected. These changes achieved maximum by 10-30 min and underwent complete reversal in 1 h. The decrease in insulin binding to Golgi fractions resulted exclusively from a change in receptor number and was accompanied by a 4- to 6-fold decrease in the content of extractable insulin in these fractions; the latter observation suggests that receptor internalization, rather than receptor synthesis, is diminished. The effects of diazoxide on plasma insulin concentration, insulin binding to Golgi fractions, and insulin content of Golgi fractions were fully prevented by tolbutamide, a stimulant of insulin secretion. These results show that acute hypoinsulinemias in rats are accompanied by changes in the subcellular distribution of hepatic insulin receptors that are opposite to those previously observed in acute hyperinsulinemias. Furthermore, both in acute hyperinsulinemic and hypoinsulinemic models, a significant correlation is observed between plasma insulin concentration on the one hand, and insulin binding to Golgi fractions as well as insulin content of Golgi fractions on the other. It is concluded that the extent to which hepatic insulin receptors are internalized is a function of their occupancy by endogenous hormone, and that, at least under acute conditions, receptor internalization is one major mechanism involved in receptor regulation. PMID- 2882997 TI - Calcitonin gene-related peptide: a potent and selective stimulator of gastrointestinal somatostatin secretion. AB - Calcitonin gene-related peptide (CGRP) exists in nerves throughout the gastrointestinal tract and pancreas, and exogenous CGRP has been reported to inhibit many endocrine and exocrine secretions of the gut and pancreas. Because somatostatin also has widespread inhibitory actions and because both gut and pancreatic somatostatin secretion may be under peptidergic control, we examined the influence of CGRP on circulating levels of somatostatin-like immunoreactivity (SLI) and on hormone output from the duodenal lobe of the dog pancreas in situ. Intravenous infusion of human CGRP in anesthetized dogs increased arterial SLI in a dose-dependent manner. During iv infusion of CGRP at 500 pmol/min, the increment of circulating SLI (change at 20 min, +175 +/- 24 fmol/ml) was composed of nearly equimolar amounts of SLI-14 and SLI-28, suggesting an effect of CGRP on both gastric and intestinal somatostatin secretion. The effect of iv CGRP (500 pmol/min) on arterial SLI exceeded those of iv CCK-8 (440 pmol/min), iv isoproterenol (10 nmol/min), and intragastric administration of acidified liver extract. In contrast, salmon calcitonin (500 pmol/min, iv) was without effect. CGRP did not stimulate pancreatic SLI output when infused iv (500 pmol/min) or when infused directly into a pancreatic artery (5 pmol/min). The pancreatic infusion of CGRP decreased insulin output slightly (change at 20 min, -21 +/- 8%), but did not affect glucagon output. We conclude that CGRP is a most effective yet selective stimulator of gastrointestinal somatostatin release, with little influence on islet function. We suggest that exogenous and possibly endogenous neuronal CGRP could exert inhibitory effects on gastrointestinal function via the release of somatostatin. PMID- 2882999 TI - Existence of somatotrope subpopulations which are differentially responsive to insulin-like growth factor I and somatostatin. AB - It is generally accepted that hypothalamic somatostatin and hepatic insulin-like growth factor I (IGF-I)/somatomedin-C act directly on the pituitary to inhibit GH release, but it is not known whether all somatotropes are responsive to these agents. In the present study, we used a reverse hemolytic plaque assay to compare the acute (8 h) effects of somatostatin and IGF-I on the release of GH from individual cells in 24-h cultures of male rat pituitaries. Treatment with these factors caused comparable dose-dependent decreases in both the rate of plaque formation and the percentage of cells which released GH. In 8-h incubations, maximal (10(-8) M) doses of IGF-I or somatostatin alone decreased the percentage of GH-releasing cells to approximately the same degree (from 34.4% in controls to 29.7% and 28.4%, respectively), yet the effects of these factors were additive when both agents were applied to the same cells (to 24.5%). When we analyzed the sizes of plaques (an index of the amount of hormone released per cell) which resulted from these treatments, we noted that somatostatin was a much greater suppressor (to 11% of control value) of GH release than IGF-I (60% of controls). Coincubation with 10(-8) M GH-releasing factor had no effect on the percentage of GH-releasing cells at 8 h but completely overrode the inhibitory effect of IGF-I on plaque size without affecting the somatostatin-induced decrease in this regard. Taken together, these data suggest that IGF-I and somatostatin act, at least in part, on separate subpopulations of rat somatotropes. Somatostatin is a much more effective inhibitor of total GH release than IGF-I and appears to affect most, if not all, somatotropes. In contrast, IGF-I acutely inhibits GH release (prevents plaque formation) from some somatotropes, but does not seem to affect the remaining GH cells. PMID- 2882998 TI - A pertussis toxin substrate regulates alpha 1-adrenergic dependent phosphatidylinositol hydrolysis in cultured rat myocytes. AB - The chronotropic response of the heart to alpha 1-adrenergic catecholamines influenced by pertussis toxin under certain conditions. In view of the fact that alpha 1-adrenergic action is mediated by the phosphatidylinositol pathway of hormone action in many cells, we examined the hypothesis that alpha-adrenergic agonists stimulate phosphatidylinositol hydrolysis in cardiomyocytes and that this effect is sensitive to pertussis toxin. Addition of norepinephrine to cultured rat ventricular myocytes prelabeled with myo-[2-3H]inositol resulted in rapid and significant accumulation of inositol phosphate (IP1) and inositol biphosphate. Norepinephrine-stimulated IP1 formation was not inhibited by propranolol, but was inhibited by alpha-adrenergic antagonists with an order of potency indicating alpha 1-adrenergic receptor subselectivity: prazosin (alpha 1; 3 nM) greater than yohimbine (alpha 2; 10 microM). The effect of norepinephrine to enhance IP1 formation was markedly attenuated in cells pretreated with pertussis toxin. Pertussis toxin also induced the transfer of ADP-ribose from NAD to a 41,000-dalton membrane protein in these cells. The concentration of pertussis toxin resulting in maximal inhibition of norepinephrine-stimulated IP1 formation correlated well with the concentration of pertussis toxin necessary to completely ADP-ribosylate a 41,000-dalton membrane protein (1 ng/ml). The range over which pertussis toxin inhibited norepinephrine-dependent IP1 formation and ADP-ribosylated the 41,000-dalton substrate was virtually identical. These observations establish a role for a 41,000-dalton pertussis toxin substrate in coupling the alpha 1-adrenergic receptor to phosphoinositol hydrolysis in myocardial cells. PMID- 2883000 TI - Glucocorticoid stimulation of growth hormone messenger ribonucleic acid levels in GH3 cells is inhibited by calcium but not by somatostatin. AB - Aside from studies of a possible synergism between T3 and glucocorticoids in regulating GH mRNA, there have been few previous studies of the modulation by hormones and other factors of glucocorticoid hormone regulation of pituitary cell GH gene expression. We have employed a serum-free medium containing no exogenously added Ca2+ to investigate whether Ca2+ or somatostatin influences the stimulation by the synthetic glucocorticoid dexamethasone of GH mRNA levels in GH3 cells. Basal levels were slightly (less than or equal to 2-fold) stimulated by CaCl2 (0.4 mM). The stimulation by dexamethasone (100 nM) of GH mRNA in GH3 cells incubated in serum-free medium with or without Ca2+ was, respectively, 20- and 25-fold. Thus, under these experimental conditions, little effect of Ca2+ on regulation by dexamethasone was observed. To further reduce Ca2+ levels in the incubation medium, EGTA (20 microM) was added to chelate residual Ca2+. In some but not all experiments, EGTA treatment yielded a slight decrease in basal GH mRNA levels. Time-course experiments performed in the presence of EGTA showed that during incubation periods with dexamethasone that yielded a detectable stimulation of GH mRNA (2-4 days), Ca2+ (0.4 mM) inhibited the dexamethasone stimulation by 3- to 5-fold. Investigations of the dose-response relationship of the effect of dexamethasone on GH mRNA performed under the same conditions showed that at dexamethasone concentrations that yielded a significant stimulation of GH mRNA (10 nM or greater), Ca2+ (0.4 mM) inhibited the dexamethasone stimulation by about 2-fold. In contrast to the inhibitory effects of Ca2+ on the stimulation by dexamethasone of GH mRNA in the GH3 cells, somatostatin had no effect at any concentration tested (1-1000 nM) on dexamethasone regulation of this mRNA. PMID- 2883001 TI - Greater in vivo than in vitro pulsatility of insulin secretion with synchronized insulin and somatostatin secretory pulses. AB - To examine the control of pulsatile insulin secretion by an intrapancreatic pacemaker, samples at minute intervals were taken from the portal vein in dogs in vivo and from an isolated perfused pancreas preparation in vitro. Anesthetized dogs had high amplitude pulsatile insulin secretion which was not consistently regular. Fourier transform analysis showed dominant 20- and 10-min periods of spectral power (P less than 0.01). After vagotomy, the relative oscillatory power was reduced from 83% to 42%, about a lower mean concentration with abolition of the 20-min oscillations. The isolated perfused dog pancreas also had oscillatory insulin secretion with oscillatory power of 12%. Autocorrelation showed regularity of in vitro insulin secretion with a period of 10-11 min (P less than 0.0001). In addition, somatostatin was secreted from the in vitro pancreas in pulses in phase with insulin (cross-correlation P less than 0.0001). These data are in accord with the theory that the pancreas has an internal pacemaker which controls insulin secretion, and that the amplitude of the oscillations is modulated by vagal control. The pacing of the islets may be coordinated by a neural network, whereas coincident pulsatile somatostatin release may temporarily suppress islet secretion and help to synchronize hormonal oscillations. PMID- 2883002 TI - In vivo biosynthesis of arginine vasopressin and oxytocin in hypothalami from intact and hypophysectomized rats. AB - The rates of incorporation of [35S]cysteine into arginine vasopressin (AVP) and oxytocin (OXT) were studied concurrently in hypothalami from intact and hypophysectomized male rats. After label injection into the third ventricle, rats were killed 0.5, 1, 2, 4, or 8 h later. The hypothalamic peptides were quantitated by specific RIA and separated by HPLC to allow quantitation of label incorporation into each peptide. In intact rats, labeling of both OXT and AVP rose rapidly to peak at 2 h; thereafter, radioactivity in both peptides declined slowly to 8 h. In hypophysectomized rats, labeling of AVP fell below that in intact animals at all time points. Labeling of OXT was somewhat below normal 2 h after label injection, but considerably above normal at 4 and 8 h. For comparison, label incorporation into somatostatin-14 (SRIF-14) and somatostatin 28 (SRIF-28) was also studied in the same animals. In intact rats, labeling of both SRIF peptides rose slowly to maximal values at 8 h. In hypophysectomized animals, labeling of each peptide was reduced substantially at all times tested. Endogenous cysteine specific activity and protein specific activity did not differ between intact and hypophysectomized animals. Immunoreactive levels of AVP and OXT in the hypothalamus were unaffected by hypophysectomy, though total SRIF like immunoreactivity was depressed. Together these results suggest that hypothalamic neurons synthesize OXT and AVP at rates much faster than those for the SRIF peptides, and that hypophysectomy has differential effects on the syntheses of cysteine-containing peptides in the hypothalamus. Specifically, the syntheses of SRIF-14 and SRIF-28 appear to be sizeably reduced in hypophysectomized rats, while that of AVP only modestly diminished. OXT synthesis may be increased. PMID- 2883003 TI - Effects on physical performance of intrinsic sympathomimetic activity (ISA) during selective beta 1-blockade. AB - In 15 healthy, not specifically trained volunteers (age: 26.6 +/- 2.7 years) single equipotent doses of a selective beta 1-blocker with intrinsic sympathomimetic activity (ISA) (200 mg Epanolol-Visacor; V) and of a selective beta 1-blocker without ISA (100 mg Metoprolol; M) were compared with placebo (P) with respect to their influence upon physical performance capacity and metabolism in a random, double blind, cross-over experimental setting. The subjects underwent three step by step incremental treadmill tests and three treadmill endurance tests until volitional exhaustion. Maximum running speed and maximum oxygen uptake were used as measures of maximum performance capacity. Running speed and oxygen uptake related to individual anaerobic threshold, and running time and running distance in the endurance tests were used as measures of endurance capacity. Both maximum and endurance performances were reduced significantly by beta-blockade. No relevant differences were discerned between V and M. The uniform reduction in exercise heart rate with both beta-blockers demonstrated the application of equipotent doses. At rest, heart rate was significantly higher under V than under M. Carbohydrate metabolism was unaffected, both beta-blockers showing equal inhibition of lipolysis during exercise. We conclude that intrinsic sympathomimetic activity has no influence upon physical performance and metabolism during selective beta 1-blockade. PMID- 2883004 TI - Acellular pertussis vaccine in adults: adverse reactions and immune response. AB - An acellular pertussis vaccine JNIH-6 containing pertussis toxin and filamentous hemagglutinin was evaluated in adult volunteers with regard to adverse reactions and antibody response. Adverse reactions were few and mild. A late onset local reaction was seen in 22 of the 47 vaccinees (47%) as compared to none of the 20 subjects receiving a placebo, the carrier solution of aluminium phosphate of the vaccine. The reaction, which manifested itself on the 6th to 8th day after vaccination, consisted in all cases of an induration and/or swelling considered insignificant by the majority of the subjects. The reaction was only found in vaccinees receiving a first dose of vaccine and was independent of the prevaccination antitoxin level. The vaccine induced a highly satisfactory antibody response to both filamentous hemagglutinin and pertussis toxin. PMID- 2883005 TI - Proton translocation by the H+-ATPase of mitochondria. Effect of modification by monofunctional reagents of thiol residues in F0 polypeptides. AB - A study is presented on the effect of chemical modification of thiol groups on proton conduction by the H+-ATPase complex in 'inside out' submitochondrial particles, before and after removal of the F1 moiety, and by F0 liposomes. The results obtained show that modification with monofunctional reagents [N ethylmaleimide, 2,2'-dithiobispyridine, mersalyl and N-(7-dimethylamino-4-methyl coumarinyl)-maleimide] of thiol residues in membrane integral proteins of F0 results in inhibition of proton conduction. Comparison of the inhibitory effects with the binding of [14C]N-ethylmaleimide to the various F0 polypeptides indicates that the inhibition of proton conduction by thiol reagents was correlated with modification of the 25-kDa, 11-kDa and 9-kDa (N,N' dicyclohexylcarbodiimide-binding protein) proteins. Involvement of the last component is supported by the observation that modification by thiol reagents depressed the binding of N,N'-dicyclo[14C]hexylcarbodiimide to the 9-kDa protein. PMID- 2883006 TI - Equilibrium constants of several reactions involved in the fermentation of glutamate. AB - The equilibrium constants of the reactions catalysed by (S)-citramalate lyase and (R)-2-hydroxyglutarate dehydrogenase were determined using the purified enzymes from Clostridium tetanomorphum and Acidaminococcus fermentans, respectively. The former constant had to be determined at high ionic strength (I). Therefore it was corrected to I = 0.1 M by applying single-ion activity coefficients estimated from literature data. The result (Kapp = 4.31 +/- 0.07 M-1; direction of citramalate formation) agreed very well with the constant of the (2R,3S)-2,3 dimethylmalate lyase equilibrium when all optical isomers were taken into account. From these and other data values for the free energies of formation (delta Gzerof) of (2S,3S)-3-methylaspartate, mesaconate and (S)-citramalate were calculated. The constant of the (R)-2-hydroxyglutarate dehydrogenase equilibrium [Kapp = (1.47 +/- 0.12)10(-12) M, direction of 2-oxoglutarate formation, I = 0.1 M] was shown to lie between those for malate and lactate dehydrogenases as expected. PMID- 2883007 TI - Subunit 4 of ATP synthase (F0F1) from yeast mitochondria. Purification, amino acid composition and partial N-terminal sequence. AB - One subunit of the membrane portion of yeast ATP synthase was purified. Structural data are reported. This subunit (subunit 4) is the fourth polypeptide of the complex when classifying subunits in order of decreasing molecular mass. Its apparent relative molecular mass is about 25,000. The polypeptide was extracted from the complex with a mixture of chloroform/methanol (1/1) and 0.5 M pyridinium acetate pH 6.0. Purification was performed with a combination of gel permeation chromatography on Sephadex G-75 and high-performance gel permeation chromatography with aqueous solvents containing 5% sodium dodecyl sulfate. The amino acid composition is reported here. The following sequence of the NH2 terminal ten residues was determined: Met-Ser-Ser-Thr-Pro-Glu-Lys-Gln-Thr-Asp. PMID- 2883008 TI - Coreconstitution of bacterial ATP synthase with monomeric bacteriorhodopsin into liposomes. A comparison between the efficiency of monomeric bacteriorhodopsin and purple membrane patches in coreconstitution experiments. AB - The conditions for coreconstitution of a bacterial ATP synthase and bacteriorhodopsin into lecithin liposomes and for light driven ATP synthesis have been optimized. A rate of maximally 280 nmol ATP min-1 mg ATP synthase-1 was achieved with monomerized bacteriorhodopsin compared with a rate of up to 45 nmol ATP min-1 mg-1 found for proteoliposomes containing bacteriorhodopsin in the form of purple membrane patches. The different rates are explained by the finding that monomeric bacteriorhodopsin is more homogeneously distributed among the liposomes than the purple membrane patches. The final activities depended on both the purification method for the two proteins and the coreconstitution procedure. Furthermore, the ratio (lipid to bacteriorhodopsin to ATP synthase) could be optimized. Light-driven ATP synthesis depends also on the type of detergent used. The best result was obtained by deoxycholate. Also the relationship between proton translocation (by bacteriorhodopsin) and ATP synthesis activity was measured. A constant H+/ATP ratio was found at higher light intensities. This ratio increased strongly at lower light intensities. PMID- 2883009 TI - Functional alpha and beta T cell chain receptor messages can be detected in old but not in young athymic mice. AB - The expression and sequences of T cell antigen receptor (TcR) alpha and beta chain genes were investigated in the spleens from congenitally athymic (nude) mice. A small number of Thy-1+ cells (approximately 7.0%) was found in nylon wool enriched spleen cells from young (8 weeks old) nude mice but no L3T4 or Lyt-2 surface antigens were detected. These nude mice expressed only a low level of 1.0 kb beta-chain mRNA and little or no alpha-gene transcripts. On the other hand the number of Thy-1+ spleen cells increased slightly (to 24%) in old (20 weeks old) nude mice and a small number of L3T4+ (10%) and/or Lyt-2+ (5%) cells were detectable. "Full length" 1.7-kb alpha-chain and 1.3-kb beta-chain messages could be found in nylon wool-enriched spleen cells from old nude mice. Sequence analysis of the cDNA revealed that no functional alpha and beta-chain genes can be detected in the spleen cells of young athymic mice while some of the old mice with nu/nu genotype are composed of completely rearranged V-(D)-J-C-gene segments which encode potentially functional proteins. Interestingly, two of three independent cDNA clones encoding the alpha chain used the same V alpha and J alpha-gene segments. These results suggest that extrathymic TcR alpha and beta chain gene rearrangements do occur, though slowly, to some extent, in nude mice and may be responsible for the limited antigen and/or H-2-related T cell functions in these old athymic mice. The data further suggests that the TcR repertoire in athymic mice may also be limited. PMID- 2883010 TI - Permissive role of D-1 receptor stimulation by endogenous dopamine for the expression of postsynaptic D-2-mediated behavioural responses. Yawning in rats. AB - Low doses of BHT 920, LY 171555 and (+)3PPP, three dopamine agonists selective for D-2 receptors, induced yawning in rats. This effect was reduced by the selective D-1 antagonist SCH 23390 but the antagonism did not exceed a 50% reduction from the control values. In contrast, the selective D-2 antagonist ( )sulpiride completely abolished agonist-induced yawning. A 6 h reserpine pretreatment (5 mg/kg i.p.), which depletes brain dopamine (DA) by about 95%, reduced agonist-induced yawning by an extent similar to SCH 23390; in the reserpinized rats, SCH 23390 completely lost the property of blocking agonist induced yawning while (-)sulpiride retained it. Two 5HT receptor antagonist, ketanserin and metergoline failed to influence agonist-induced yawning. The reportedly selective D-1 agonist, SKF 38393, failed to induce yawning in normal rats as well as in rats pretreated with reserpine 6 or 16 h earlier. If one excludes that SCH 23390 and the D-2 agonists interact with the same DA-receptors, the data are consistent with the possibility that stimulation of D-1 receptors by endogenous DA plays a permissive-facilitatory role for the behavioural expression of D-2 receptor activation. PMID- 2883011 TI - Reduction of apparent indicators of liver cirrhosis in rats by the arachidonate lipoxygenase inhibitor BW755C. AB - We have compared the effects of BW755C, a dual inhibitor of the arachidonic acid cyclo-oxygenase and lipoxygenase, with the effects of colchicine and indomethacin on the reversion of the biochemical and histochemical signs of rat liver cirrhosis. This was induced by i.p. administration of CCl4 for 11 weeks. At this point the rats were divided into four groups (10 animals each). CCl4 administration was continued for one month along with either colchicine, BW755C or indomethacin. No additional treatment was given to the control group. BW755C consistently improved all the parameters studied. Although colchicine also improved all but two markers (serum ALT activity and serum proteins) it ranked lower than BW755C in most of them. Indomethacin only modified favourably serum alkaline phosphatase activity, serum proteins, cholesterol and bilirubins and liver collagen content. The effects of BW755C could be mainly attributed to the inhibition of the lipoxygenase pathway. A common feature of colchicine, adrenal steroids and BW755C was the ability to inhibit the formation of leukotriene and other lipoxygenase products. The possibility that this property might contribute to their anti-cirrhotic actions is discussed. PMID- 2883012 TI - A comparison of the neurotoxic potential of methylenedioxyamphetamine (MDA) and its N-methylated and N-ethylated derivatives. AB - Three psychoactive amphetamine congeners were evaluated for their ability to cause long-term changes in several neurochemical parameters indicative of central serotonergic function. Two weeks after multiple doses (10 mg/kg) of 3,4 methylenedioxyamphetamine (MDA) or its N-methylated derivative, 3,4 methylenedioxymethamphetamine (MDMA), selective and dramatic decreases were observed in regional brain tryptophan hydroxylase (TPH) activities, and in corresponding concentrations of 5-hydroxytryptamine (5-HT) and its primary metabolite, 5-hydroxyindoleacetic acid (5-HIAA). However, the N-ethylated derivative of MDA, N-ethyl-3,4-methylenedioxyamphetamine (MDE), was much less potent in its ability to lower brain hydroxyindoles, and in most regions examined did not significantly affect TPH activity. The neurotoxic implications of these results are discussed. PMID- 2883014 TI - The anxiolytic beta-carboline ZK 93423 prevents the stress-induced increase in dopamine turnover in the prefrontal cortex. AB - The effects of electric foot-shock on the activity of the mesocortical dopaminergic (DAergic) neurons were estimated by measuring the changes in dihydrophenylacetic acid (DOPAC) and DA content in the prefrontal cortex of the rat. A marked rise in DOPAC content (+80%) and a significant decrease in DA levels (-23%) were observed after a 20 min foot-shock session. These effects were completely prevented by pretreatment with diazepam (5 mg/kg i.p.). ZK 93423, a recently synthesized beta-carboline with benzodiazepine-like properties, prevented the decrease in DA content induced by foot-shock at the dose of 20 mg/kg. Moreover, the stress-induced increase in DOPAC levels was partly or completely blocked by pretreatment with 20 or 40 mg/kg of ZK 93423, respectively. These results provide further support for the view that the mesocortical DAergic system can be modulated by drugs that selectively interact with the benzodiazepine recognition site. PMID- 2883013 TI - Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression. AB - Previous results have suggested that behavioural adaptation to restraint might be promoted by post-restraint stimulation of 5-HT1A receptors. Therefore, rats were restrained for 2 h and injected with vehicle or 60-1,000 micrograms/kg of the 5 HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) s.c. Vehicle treated restrained rats showed reduced locomotor activity and increased defaecation in an open field test the day after the end of restraint. A single injection of 250 or 1,000 micrograms/kg 8-OH-DPAT attenuated these effects. The above locomotor deficits were also attenuated by chronic pretreatment with the antidepressants desipramine and sertraline but not by a single treatment with desipramine or the benzodiazepine anxiolytic drugs chlordiazepoxide and diazepam; none of these treatments unambiguously reversed stress-induced increases in defaecation. Evidence suggests that the above action of 8-OH-DPAT is mediated by 5-HT1A receptors since it was antagonised by the 5-HT1A antagonist spiperone but not by the 5-HT2 antagonist ketanserin and was not mimicked by the 5-HT1B agonist RU 24969. However, the 5-HT1A agonists buspirone and TVXQ 7821 (ipsapirone) and the non-specific 5-HT agonist quipazine all possess similar properties to 8-OH DPAT in this test. The results suggest that 5-HT1A agonists may have rapid antidepressant properties. PMID- 2883015 TI - Effects of triethyltin on brain octopamines and their metabolism in the rat. AB - The effects of triethyltin given acutely on the cerebral level of p- and m octopamines were studied in rats. These octopamines were reduced drastically in hypothalamus and brainstem, while noradrenaline and dopamine were only slightly decreased. No important changes were observed in the activities of tyrosine hydroxylase, dopamine beta-hydroxylase or monoamine oxidase. However, the activity of aromatic L-amino acid decarboxylase was significantly reduced. The addition of the inhibitor of dopa decarboxylase, Ro 44602, caused a total inhibition of this enzyme activity. These results are discussed in terms of the possible use of the triethyltin-induced cerebral oedema as a model for the study of some aspects of the phenolamine changes related to cerebral oedema processes. PMID- 2883017 TI - New aspects on the treatment of inflammatory reactions and broncho-obstruction in bronchial asthma. PMID- 2883016 TI - CFU-mix are no better than CFU-GM in predicting hemopoietic reconstitutive capacity of peripheral blood stem cells collected in the very early remission phase of acute nonlymphoblastic leukemia. AB - High levels of circulating myeloid progenitor cells (CFU-GM) occur during the very early remission phase of acute nonlymphoblastic leukemia (ANLL). Autologous stem cell rescue using blood cells collected during this phase has shown that successful hemopoietic reconstitution can be achieved, but a higher CFU-GM dose appears to be required than when bone marrow cells are used. This suggests that during very early remission, the level of marrow repopulating pluripotent stem cells (PSC) in blood does not undergo the same amount of increase as does the CFU GM. This study set out to determine whether the levels of the multilineage progenitor cell (CFU-Mix) would be better indicators of the PSC in these cells than the CFU-GM. Serial peripheral blood CFU-Mix and CFU-GM measurements were carried out in six ANLL patients during very early remission. The levels of peripheral blood CFU-Mix showed a mean 12-fold increase, as compared to a mean 20 fold increase in the CFU-GM. The timing of the increase in the CFU-Mix paralleled that of the CFU-GM. These findings suggest that the CFU-Mix is no better than the CFU-GM in predicting PSC levels during very early remission of ANLL, and is closer to the CFU-GM than to the PSC in ontogeny. PMID- 2883018 TI - Modulation of postdecapitation convulsions in rats by alpha-adrenergic and 5 hydroxytryptamine1A agents. AB - Postdecapitation convulsions were analyzed in rats after the administration of a variety of adrenergic and serotonergic agents. Drugs were selected on the basis of their relative affinities for 5-hydroxytryptamine1A, alpha 2-adrenergic and/or alpha 1-adrenergic receptors. The 5-hydroxytryptamine1A-selective agonists, 8 hydroxy-N,N-dipropyl-2-aminotetralin and buspirone, significantly increased the duration of the convulsions. The alpha 2-adrenergic antagonists, yohimbine and corynanthine, had no affect on either the latency or duration of the convulsions. By contrast, each of the three alpha 1-adrenergic agents increased the latency and decreased their duration. However, the order of potency was WB 4101 greater than ipsapirone greater than prazosin and this rank order did not correlate with drug potencies for the alpha 1-adrenergic receptor as determined by radioligand binding studies. The high potency of both ipsapirone and WB 4101 in inhibiting the postdecapitation convulsions may relate to the combined effects of the drugs at both alpha 1-adrenergic and 5-hydroxytryptamine1A receptors. PMID- 2883020 TI - Entamoeba histolytica: cytopathogenicity and lectin activity of avirulent mutants. AB - Three clones of Entamoeba histolytica (L-6, C93, C919) were isolated by mutagenesis with ethyl methanesulfonate from the axenic strain HM1:IMSS and were studied for adherence, cytolytic, and soluble galactose inhibitable lectin activity. Avirulent clones adhered to and killed fewer Chinese hamster ovary cells than HM1:IMSS (P less than 0.01). However, only C919 was deficient in adherence to red blood cells. Galactose (1.0 g) completely inhibited adherence of all the mutants to Chinese hamster ovary cells; however, adherence to erythrocytes was only partially inhibitable by galactose. Avirulent mutants were more susceptible to being killed by human neutrophils in vitro (P less than 0.01 compared to HM1:IMSS). Soluble protein preparations from all the avirulent mutants were markedly less mitogenic for human lymphocytes and had lower lectin activity for Chinese hamster ovary cells compared to the HM1:IMSS wild type (P less than 0.01 for each activity with each mutant). Indirect immunofluorescence with a monoclonal antibody (F-14) that recognizes the Gal/GalNAc lectin was positive for L-6 and C919. These findings utilizing avirulent mutants of E. histolytica further support a role for the amebic galactose inhibitable lectin in the in vivo pathogenesis of amebiasis. PMID- 2883019 TI - Cortical neurons exposed to glutamate rapidly leak preloaded 51chromium. AB - The acute toxic effects of excess glutamate exposure on cortical neurons in culture was followed using a novel adaptation of the 51chromium efflux assay. Although the acute, sodium-dependent phase of glutamate neurotoxicity may contribute to several acute disease settings, including sustained seizures and stroke, functional aspects of the phenomenon have not been previously studied. We report here that the earliest morphologic sign of glutamate neurotoxicity, neuronal swelling, is accompanied by a large efflux of complexed 51chromium from preloaded neurons in the first hour after exposure, and that this efflux is detectable as early as 15 min after the onset of glutamate exposure. We suggest that this pathological burst of 51chromium may result from glutamate-induced "leakiness" of neuronal cell membranes. PMID- 2883022 TI - Medullary thyroid carcinoma in the Syrian golden hamster: an immunohistochemical study. AB - Spontaneously occurring thyroid neoplasms exhibiting solid and/or anaplastic growth patterns in the Syrian golden hamster have been thought to be derived from follicular cells. Eight neoplasms of this type have been analyzed immunohistochemically and have been classified as medullary thyroid carcinomas (MTC) on the basis of their content of calcitonin (CT). Well differentiated MTCs in this species were composed of polyhedral cells showing uniform CT immunoreactivity while the poorly differentiated MTCs most often had spindle patterns of growth with marked variation in CT immunoreactivity. Both well and poorly differentiated MTCs contained entrapped follicles which were CT negative. In contrast to MTC in the rat and in humans with familial MTC, the tumors in hamsters were not associated with C-cell hyperplasia. The Syrian golden hamster may, therefore, serve as a useful model to study the factors which are responsible for the development of spontaneous (non-familial) MTC. PMID- 2883021 TI - Schistosoma mansoni: effects of bromolysergic acid diethylamide, verapamil, and Ca2+-free solution on the motor activity of the isolated male worm induced by electrical stimulation and oxamniquine. AB - Electrical stimulation and oxamniquine effect the motor activity of isolated Schistosoma mansoni. Electrical stimulation produced contractions that increased with stimulus intensity. Oxamniquine (10(-4) M) produced an increase in basal tonus and in the frequency and amplitude of the worm's spontaneous contractions. Incubation in the absence of calcium produced a decrease in the basal tonus, abolished the spontaneous contractions of S. mansoni, and abolished the mechanical response induced by electrical stimulation and oxamniquine. The effects of electrical stimulation and oxamniquine were, respectively, significantly reduced and abolished by 10(-6) M verapamil (a calcium channel blocking agent). Bromolysergic acid diethylamide (3 X 10(-5) M), a serotonin blocking agent, reduced the motor response induced by high intensity electrical stimulation and blocked the response induced by oxamniquine. The effects of low intensity electrical stimulation were not modified in the presence of bromolysergic acid. We think that external Ca2+ is important for basal tonus, for spontaneous motor activity, and for motor responses of S. mansoni induced by electrical stimulation and oxamniquine. Serotonin may be important for mechanical responses induced by high intensity electrical stimulation and for responses induced by oxamniquine. PMID- 2883023 TI - Deficiency of membrane-bound dipeptidyl aminopeptidase IV in a certain rat strain. AB - The activity of membrane-bound dipeptidyl aminopeptidase IV (EC 3.4.14.5) was found to be markedly reduced in the Fischer 344 rat strain compared with that in the Wistar strain. Analysis of membrane proteins by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Ouchterlony immunodiffusion revealed the specific absence of this enzyme molecule in the Fischer 344 strain. PMID- 2883024 TI - Inhibition by SMS 201-995 of normal mammary gland growth in mice. AB - Twice daily s.c. injection of 5 ng or 50 ng of SMS 201-995 between 25 and 55 days of age induced a significant retardation of normal mammary gland growth in C3H/He virgin mice, associated with the reduced plasma GH level. Meanwhile, plasma prolactin level and the pattern of estrous cycle were affected little by SMS treatments. The results indicate an involvement of GH in normal mammary gland growth in mice. PMID- 2883025 TI - The amino-acid sequences of sculpin islet somatostatin-28 and peptide YY. AB - Two pancreatic peptides, somatostatin-28 and peptide YY, have been isolated from the Brockmann bodies of the teleost fish Cottus scorpius (daddy sculpin). Following purification by reverse-phase HPLC, each peptide was sequenced completely through to the carboxyl-terminus by gas-phase Edman degradation. Somatostatin-28 was the major form of somatostatin detected and is similar to the gene II product from anglerfish. Peptide YY (36 amino acids) more closely resembles porcine neuropeptide YY and intestinal peptide YY than it does the pancreatic polypeptides. PMID- 2883026 TI - Pyrroloquinoline quinone and molecules mimicking its functional domains. Modulators of connective tissue formation? PMID- 2883027 TI - Expression of insulin-like growth factor-I and -II genes in rat medullary thyroid carcinoma. AB - Several types of cancer cells produce polypeptide growth factors and often the same cells have functional receptors for the released growth factor (autocrine secretion). We have studied expression of genes encoding somatomedin-C/insulin like growth factor-I (Sm-C/IGF-I) and IGF-II, in rat medullary thyroid carcinomas (MTCs) in different stages of tumour differentiation. RNAs hybridizing specifically to an IGF-I cDNA probe were detected in 6 out of 7 differentiated MTCs and IGF-II related RNAs were demonstrated in 5 out of these 7 differentiated MTCs. In 5 anaplastic MTCs no IGF RNAs were detected, except for a small amount of IGF-II related RNA in one tumour. PMID- 2883029 TI - A 1H-NMR study of the solution conformation of secretin. Resonance assignment and secondary structure. AB - The solution conformation of the 27 residue polypeptide hormone secretin has been investigated by 1H-NMR spectroscopy under conditions where it adopts a fully ordered structure as judged by circular dichroism spectroscopy, namely in an aqueous solution of 40% (v/v) trifluoroethanol. Using a combination of two dimensional NMR techniques the 1H-NMR spectrum of secretin is completely assigned and its secondary structure is determined from a qualitative interpretation of the nuclear Overhauser enhancement data. It is shown that under these conditions secretin adopts a conformation consisting of an N-terminal irregular strand (residues 1-6) followed by two helices (residues 7-13 and 17-25) connected by a 'half-turn' (residues 14-16); the last two residues (26 and 27) are again irregular. This conformation is shown to be very similar to that of glucagon in perdeuterated dodecylphosphocholine micelles and to that of the active 1-29 fragment of growth hormone releasing factor in 30% (v/v) trifluoroethanol: PMID- 2883030 TI - [First aid in injuries by poisonous animals]. PMID- 2883028 TI - A positive relationship between protein synthetic rate and intracellular glutamine concentration in perfused rat skeletal muscle. AB - During muscle-protein wasting associated with injury and disease the distribution ratio of free glutamine between muscle and blood falls. In pursuing possible consequences of this, we investigated the relationship between the rate of muscle protein synthesis and intramuscular glutamine concentration, manipulated acutely in the isolated perfused rat hindquarter. Increasing perfusate glutamine from 0.67 to 5.0 mM caused a 200% increase in intracellular glutamine and a 66% increase in protein synthesis in the absence of insulin; in the presence of insulin a 30% increase in intramuscular glutamine was accompanied by an 80% increase in protein synthesis. Analysis of variance of the results confirmed the existence of positive relationships between intramuscular glutamine and protein synthesis in the presence or absence of insulin. Control of the size of the intramuscular free pool of glutamine may be important in determining the muscle protein mass. PMID- 2883031 TI - Cost effectiveness of the bio-environmental control of malaria in Kheda district, Gujarat. PMID- 2883032 TI - Malaria situation in Meerut district villages (U.P.). PMID- 2883033 TI - An adaptation of the gel diffusion technique for identifying the source of mosquito blood meals. PMID- 2883034 TI - Bio-environmental control of malaria in Nadiad, Kheda district, Gujarat. PMID- 2883035 TI - Transglutaminase activity and embryonal carcinoma cell differentiation. AB - Murine embryonal carcinoma (EC) cells induced to differentiate by retinoic acid (RA) modulate transglutaminase (TGase) activity shortly after exposure to the inducer. Compounds that inhibit TGase enzyme activity in vitro can successfully block RA induced EC cell differentiation in culture. These observations suggest that TGase may play a role in mediating RA induced EC cell differentiation. PMID- 2883036 TI - A characterization of gamma-glutamyltranspeptidase in normal, perinatal, premalignant and malignant rat liver. AB - gamma-Glutamyltranspeptidase displays the following order of activity in tissues of the Fischer 344 rat: kidney much greater than small intestine much greater than cerebral cortex = testis greater than lung much greater than liver = heart. The activity of the hepatic enzyme in rats is: 4-fold higher in females than males; 4-fold higher in male Wistar, Sprague-Dawley and Zucker rats than male Fischer 344 rats; increased 10-fold in very old vs young male Fischer 344. The hepatic enzyme displays significant species variation: the mouse and rat liver enzymes are similar and low in activity, while duck, dog, pig and beef enzymes are 7, 13, 86 and 92-fold higher, respectively, in activity than the male Fischer rat liver enzyme. A liver plasma membrane isolation procedure has been devised which selects for the sinusoidal face of the liver parenchymal cell as assessed by marker enzyme analysis: for these plasma membranes the purification of gamma glutamyltranspeptidase is 21.5 and the recovery is 42% indicating that this is the cellular and subcellular locus of the enzyme in rat liver. The characteristics of the liver plasma membrane from female rats are: pH optimum of 8.0; classical Michaelis-Menten kinetics; Km of 1.43 mM and Vmax of 33.3 nmol X mg-1 X min-1. In Fischer 344 rats, gamma-glutamyltranspeptidase activities are elevated over adult levels in perinatal liver: in fetal liver homogenates and plasma membranes the activities are increased 179 and 109-fold, respectively. The activity peaks just after birth and declines rapidly over the first 15 postnatal days. The activity of the liver enzyme in the male Fischer 344 rat exhibits a progressive increase throughout diethylnitrosamine-induced hepatocarcinogenesis: it is increased 7.8-fold in homogenates and 5.4-fold in plasma membranes at the early premalignant stage; 74-fold in homogenates and 31-fold in plasma membranes at the later hyperplastic nodular premalignant stage; and 174-fold in homogenates and 61-fold in plasma membranes at the hepatoma stage. The gradual drop in purification during hepatocarcinogenesis is associated with the appearance of the enzyme in the blood. PMID- 2883037 TI - Different effects of 2,4-dinitrophenol on rat liver mitochondrial oxidation of various substrates: succinate and glutamate vs 3-hydroxybutyrate and glycerol 3 phosphate. AB - In homogenate and isolated mitochondria from the liver of male and female rats of Wistar and August strains, a higher uncoupled vs State 3 oxidation of succinate and glutamate and lower that of 3-hydroxybutyrate and glycerol 3-phosphate were observed. The optimal concentration of 2,4-dinitrophenol (DNP) was in the range 7 12 microM for 3-hydroxybutyrate oxidation and 50-100 microM for succinate or glutamate oxidation. PMID- 2883038 TI - Release of iron from endosomes is an early step in the transferrin cycle. AB - Transferrin bound to K 562 cells at 4 degrees C was internalized quickly on temperature shift to 37 degrees C. Endosomes were isolated according to two different procedures. The endosome fraction was shown to be heterogeneous and consisted of two vesicle populations, differing in density properties and iron content. Iron was partially released from endosomes to the supernatant after 3 and 5 min endocytosis. Isolated endosomes, still capable of internal acidification, did not release iron on incubation with ATP. However, endosomes did release iron on incubation with the iron chelator pyridoxal-isonicotinoyl hydrazone. Gel-filtration of solubilized endosomes demonstrated the presence of the transferrin-transferrin receptor complexes, free transferrin and free low molecular weight iron. PMID- 2883039 TI - Does grand multiparity affect fetal outcome? AB - Low birthweight and stillbirth rates of 16,647 Jerusalem deliveries were examined by birth-order comparing longitudinal to cross-sectional data. Six hundred fifty seven complete sibships of 7 or more were assessed, including 95 sibships from the socio-economically homogeneous ultraorthodox Jewish community of Mea Shearim. In both cross-sectional and longitudinal studies grandmultiparas were not at increased risk for low birthweight, but did have a higher frequency of stillbirths. PMID- 2883040 TI - Fetal salvage with cervical cerclage. AB - A prospective study to evaluate the fetal salvage rate, cervical morbidity and cesarean section rate in patients with cervical incompetence using a cerclage procedure was conducted at the Jos University Teaching Hospital, Jos, Nigeria. The study group consisted of 71 patients who gave a history suggestive of cervical incompetence, had a dilated cervix at booking and included emergency patients in whom the cervix had dilated because of a febrile illness but had never undergone a cervical cerclage procedure. The fetal salvage rate was 23.7% in pregnancies occurring before and 94.4% after cervical cerclage procedure was performed. There were 57 term pregnancies, 10 pre-term deliveries, and 4 abortions. The study clearly demonstrates the beneficial effects of cervical cerclage operations in patients who have suffered from preventable fetal losses because their incompetent cervix was undiagnosed. Our results were compared with those of other series. The diagnosis of cervical incompetence is discussed with particular emphasis on the use of screening tests in the detection and identification of cervical incompetence. PMID- 2883041 TI - Relationship of vaginal pH and Papanicolaou smear results to vaginal flora and pregnancy outcome. AB - Prematurity is a major cause of perinatal morbidity. Studies have implicated components of the vaginal flora in the etiology of some cases of preterm birth. Current scoring systems do not include factors which directly reflect the vaginal flora. Since Papanicolaou smears and the vaginal pH may be affected by the vaginal flora and are easy tests to perform, we studied their relationship to vaginal flora and pregnancy outcome. Among 231 patients, those with a vaginal pH greater than or equal to 4.4 were significantly more likely to carry Trichomonas vaginalis (P less than 0.03); Bacteroides species (P less than 0.01), and Mycoplasma hominis (P less than 0.001), and to have premature rupture of the membranes (P less than 0.01), and preterm rupture of the membranes (P less than 0.05). Patients with atypia reported on Papanicolaou smear more frequently carried M. hominis (P less than 0.01), and had premature rupture of the membranes (P less than 0.01). Although the high sensitivity and negative predictive value of those tests may make them useful additions to current scoring systems, their low specificity prevents them from being independent predictors of risk. PMID- 2883042 TI - Ultrasonic assessment of cervix in "at risk" patients. AB - One hundred seventy patients were considered to be at risk of cervical incompetence from their previous history. They were scanned serially from the first trimester to 36 weeks gestation. Of the 170, 105 patients (61.8%) were found to have defective cervix (the length of cervix, width of the cervix, and cervical canal at the level of the internal cervical os, and herniation of amniotic membrane with or without fetal parts into the cervical canal). Of the 105 patients diagnosed to have defective cervix (possible cervical incompetence), 22 patients (21%) aborted, 48 patients (45.7%) had to have cervical cerclage, 26 patients (24.8%) had preterm delivery and the remaining 9 patients (8.5%) had no problems during pregnancy. The remaining 65 patients (38.2%) did not have ultrasonic evidence of cervical incompetence and 3 aborted and only 2 patients delivered between 35 and 37 weeks gestation while 60 patients delivered between 37 and 42 weeks gestation. These 65 patients would have had cervical cerclage on the basis of the clinical history alone, but in only 6, cervical cerclage was inserted. PMID- 2883043 TI - Treatment of hypertension in pregnancy with methyldopa: a randomized double blind study. AB - Twenty-five patients whose pregnancies were complicated by chronic hypertension were entered in a double-blind study and randomly allocated to treatment with methyldopa (Aldomet) or placebo. Thirteen patients were in the treatment group and 12 in the placebo group. The two groups showed no significant difference in demographic and pretreatment laboratory profiles. Methyldopa-treated patients registering in the first trimester had a significant reduction in the mean arterial pressure (MAP) during the second and third trimesters (P less than 0.025). No significant differences in birth weight (BW), ponderal index (PI) were found when results were corrected for gestational age (GA), race, and sex. The mean GA was significantly prolonged in the methyldopa-treated group by 10.3 days (P less than 0.05). The frequency of superimposed pre-eclampsia was similar in both groups (33.3% vs. 38.4%). However, 75% of the superimposed pre-eclampsia occurred antepartum in the placebo group, while 80% of the methyldopa-treated group developed superimposed pre-eclampsia intrapartum. The results of this small study suggest that the treatment of hypertension in pregnancy may reduce MAP and possibly delay the occurrence of superimposed pre-eclampsia and thus afford a prolongation of the pregnancy. PMID- 2883044 TI - Pregnancy termination: results of a community-based study in Lagos, Nigeria. AB - A community survey in the Shomolu area of Lagos Nigeria showed the incidence of induced abortion to be 5.6%. Most of the abortions were carried out under medical supervision, using a combination of methods. Reasons for the abortions suggest that many were carried out on pregnancies that could have been prevented. PMID- 2883045 TI - Laparoscopic evaluation of the tuboperitoneal factor in infertile Nigerian women. AB - Laparoscopy has become the most important investigative tool for the evaluation of tubal disease in developed countries of the world. In this report of 218 diagnostic laparoscopies performed on infertile Nigerian women, bilateral tubal occlusion was found in 35.3% and unilateral occlusion in 9.6%. Pelvic adhesions were present in 55.0% out of which 25.2% and 21.1% were moderate or severe, respectively. Endometriosis and uterine fibroids were present in 1.4% and 26.6% of patients, respectively. The implications of these findings for management of tubal disease in Nigerian women is discussed. PMID- 2883046 TI - Use of echosonography to monitor uterine placement of intrauterine devices after immediate postpartum insertions. AB - A study designed to monitor uterine placement of IUDs inserted immediately postpartum using echosonography was conducted at the Hospital de Gineco Obstetricia No. 23, "Dr. Ignacio Morones Prieto" in Monterrey, Mexico. TCu220 and Delta T IUDs were randomly assigned to, and inserted in women immediately following a normal vaginal delivery. Ultrasound examinations were to be performed within 60 min postinsertion, at 24 h postinsertion and at 1- and 3-month follow up visits. There were no differences in the expulsion rates of the two device groups. Data are presented on the readings taken at the ultrasound examinations of the distance between the fundus and the upper part of the stem of the T. These differences differed significantly between the two device groups at the first ultrasound reading only (P less than or equal to 0.01). No relationship was found between the incidence of expulsion and the distance between the IUD and the fundus at any of the readings. PMID- 2883048 TI - Is maternal alkalosis harmful to the fetus? AB - Normal pregnancy is characterized by a compensated respiratory alkalosis. The effect of maternal alkalosis on the fetus is less well understood than the more common problem of maternal acidosis. We present a case of maternal alkalosis, complicated by bronchial asthma, in which the fetus was stillborn. The pathophysiology of this condition is discussed with data to support the potential harm of maternal alkalosis in pregnancies complicated by a fetus with borderline reserve. In such instances, the fetus should be carefully monitored and consideration might be given to therapy such as the use of acetozolomide, discouraging hyperventilation by the mother and even early delivery of the fetus. PMID- 2883047 TI - A comparison between Nova T and Copper T 200 Ag in Hungary. AB - In a comparative use-effectiveness study, 855 Nova T and 883 TCu 200 Ag devices were inserted in a randomised sequence. By the end of the first year the gross rate of unplanned pregnancy was 1.1 per 100 users of Nova T and 2.1 per 100 users of TCu. After 2 years the pregnancy rates for Nova T and TCu were 3.1 and 4.8 per 100 users, respectively. Although there was no statistically significant difference between the rates for the two devices, they suggest a higher contraceptive efficacy for Nova T. PMID- 2883049 TI - Urethral prolapse in the premenarcheal female. AB - Urethral prolapse in the premenarcheal female manifests as vaginal bleeding and a periurethral mass. In the past, the recommended management was surgical excision or cautery. However, conservative management has been shown to have excellent results. Five premenarcheal patients with urethral prolapse treated by conservative therapy are presented. Treatment regimen consisted of local hygiene with sitz baths, hexachlorophene soap, topical providone iodine and estrogen cream. There were no complications or recurrences. Surgery is not warranted in the treatment of urethral prolapse in the premenarcheal female. Medical management is equally effective and less traumatic in this age group. PMID- 2883051 TI - Sodium fluoride in delayed measurement of umbilical blood gases. AB - In blood samples stored at 5 degrees C with 20 mM sodium fluoride, only small changes in blood gas measurements were observed over 24 h. Most of the changes occurred within the first 2 h after collection. In samples stored at 5 degrees C without fluoride, blood gas measurements showed continuous changes over the 24-h period. PMID- 2883050 TI - Patent ductus arteriosus after prolonged treatment with indomethacin during pregnancy: case report. AB - Indomethacin was administered to suppress premature uterine contractions in a twin pregnancy from the 27th until the 32nd week of pregnancy. Patent ductus arteriosus was diagnosed after delivery in one twin and persisted patent for a period of 4 weeks. A hypothesis of the constrictive influence of prostaglandin synthetase inhibitors on the fetal ductus arteriosus during intrauterine and neonatal periods is suggested. PMID- 2883052 TI - Commitment to differentiation induced by retinoic acid in P19 embryonal carcinoma cells is cell cycle dependent. AB - The rate at which P19 embryonal carcinoma cells in monolayer culture become anchorage dependent during differentiation induced by retinoic acid (RA) was investigated. In both nonsynchronized cultures and cultures synchronized by mitotic selection, the ability to grow in semisolid medium, characteristic of the malignant stem cell, decreased after a lag period of about 12 hr in the continuous presence of RA, prior to an increase in cell generation time. However, striking differences between synchronized and nonsynchronized cultures were observed in their commitment to differentiation following RA removal. After only 2 hr of exposure to RA, synchronized cells continued a program of differentiation in which they became anchorage dependent, while at least 24 hr of exposure was required for exponentially growing cells to become similarly committed. Induction of anchorage dependence by RA was also strikingly cell cycle dependent; 2 or 4 hr of exposure of synchronized cells to RA in G1 phase, when the intrinsic capacity for soft agar growth is low, was sufficient to commit cells to anchorage dependence, but a similar exposure in S phase was not. Together, these results suggested that interactions between cells in different cell cycle phases in asynchronous cultures influenced commitment since exposure to RA for more than one cycle (13 hr) was required for all cells to become anchorage dependent. Increased plasminogen activator secretion and epidermal growth factor binding, markers of certain differentiated cell types, increased only 3 and 5 days after RA addition, respectively, and were not induced by pulsed exposure to RA of less than 24 hr, even in synchronized cells. PMID- 2883054 TI - Localization of Xenopus homoeo-box gene transcripts during embryogenesis and in the adult nervous system. AB - Tissue distribution and localization of RNAs from the Xeb1 homoeo-box-containing gene were monitored with Northern blots and in situ hybridization. Xeb1 transcript distribution in larval stage embryos was established by blotting RNAs extracted from microdissected embryos. Those transcripts are restricted to a limited number of embryonic regions such as the dorsal trunk. The tissue/cell localization of Xeb1 transcripts was then monitored at several embryonic stages with in situ hybridization methods using [35S]RNA probes. These homoeo-box transcripts accumulated in a progressive and dynamic fashion. First localized in late gastrulae, they are distributed along the neural tube and in caudal mesoderm at later stages. By the swimming tadpole stage the spatial distribution of the homoeo-box transcripts is limited to specific regions of the central nervous system. Adult spinal cord shows the signal in specific neurons in the ventrolateral field of the gray matter. PMID- 2883053 TI - Establishment of embryonic stem cell lines from preimplantation mouse embryos homozygous for lethal mutations in the t-complex. AB - We have determined the frequency at which embryonic stem cell (ESC) lines can be established from inner cell masses (ICMs) isolated from blastocysts homozygous for lethal mutations in the mouse t-complex. Approximately one-third of the expected number, 3/29, of the ESC lines established from embryos obtained by inter-se mating of +/tw18 mice are homozygous for the tw18 haplotype. These tw18/tw18 ESC lines form a variety of cell types in vitro and in vivo, including mesodermal derivatives such as cartilage and muscle. On the basis of these and data from other studies, we suggest that the normal function of the gene represented by the tw18 lethal allele is required for multiplication/survival of mesodermal precursors in the embryo rather than the specification of the mesodermal lineage, and that the lethal effects of this mutation are expressed in only the highly structured environment of the early postimplantation embryo. In studies of the lethal tw5 haplotype, we found that 2/2 ESC lines obtained are mutant homozygotes. Analysis of these data, in conjunction with the results of our earlier study (Magnuson, T., Epstein, C. J., Silver, L. M., and Martin, G. R. (1982), Nature (London) 298, 750-753), suggests that homozygosity for the genes found in the tw5 haplotype does not reduce cell viability. By contrast, 0/16 ESC lines isolated from embryos obtained from matings of +/t0 mice are mutant homozygotes. Analysis of the genotypes of ICM-derived primary stem cell colonies suggests that t0 homozygous ICM cells are unable to undergo sufficient proliferation in vitro to give rise to ESC lines. PMID- 2883055 TI - Greater efficacy of pulsatile insulin in type I diabetics critically depends on plasma glucagon levels. AB - The aim of this study was to investigate the role of plasma glucagon levels on the blood glucose response to intravenous insulin administered continuously or in a pulsatile manner. Six type I diabetic patients proven to have no residual insulin secretion were investigated. Endogenous glucagon secretion was inhibited by a continuous intravenous infusion of somatostatin (100 micrograms/h) and replaced by exogenous infusions of the hormone at three different rates (7.5, 4.5, and 2.5 micrograms/h), resulting in three different plasma glucagon steady state levels (i.e., approximately equal to 200, approximately equal to 130, and approximately equal to 75 pg/ml, respectively). Each subject, in random order and on different days, was infused intravenously with regular human insulin either continuously (0.17 mU X kg-1 X min-1) or with the same amount of insulin infused in a pulsatile manner (0.85 mU X kg-1 X min-1 during 2 min followed by 8 min during which no insulin was infused). At plasma glucagon levels approximately equal to 200 pg/ml, blood glucose rose from approximately 10 to approximately 13 mM without any difference between the two modalities of insulin infusion. For plasma glucagon levels approximately equal to 130 pg/ml, plasma glucose remained steady throughout the experiments, but during the last 40 min, plasma glucose levels were significantly lower when insulin was administered intermittently. This greater blood glucose-lowering effect of pulsatile insulin occurred earlier and was more pronounced for plasma glucagon levels averaging 75 pg/ml. We conclude that the greater hypoglycemic effect of insulin administered intravenously in a pulsatile manner in type I diabetics critically depends on plasma glucagon circulating levels. PMID- 2883056 TI - Cytosolic free-calcium concentrations in normal pancreatic islet cells. Effect of secretagogues and somatostatin. AB - We have assessed the effect of somatostatin on glucose-, potassium-, forskolin-, and dibutyryl cAMP-induced changes in cytosolic free [Ca2+] in normal rat pancreatic islet cells with the new Ca2+ indicator fura 2. The cytosolic free [Ca2+] in islet cells incubated with nonstimulatory concentrations of glucose (30 mg/dl) ranged from 54 to 64 nM. In the presence of extracellular Ca2+ (1 mM), glucose (300 mg/dl) rapidly increased the cytosolic free [Ca2+] to a level of 90 110 nM. In the absence of extracellular Ca2+, glucose failed to increase the cytosolic free [Ca2+], which remained at a level of 55-60 nM. Somatostatin inhibited glucose-induced increases in cytosolic free [Ca2+] in a dose-dependent manner (maximal inhibition was 34%). Half-maximal inhibition was observed at 10( 9) M somatostatin, which correlated well with somatostatin binding to islet cells (Kd = 2.6 X 10(-10) M). Potassium (50 mM) rapidly increased the cytosolic free [Ca2+] to 110-120 nM, and its effect was not influenced by the presence of somatostatin. Forskolin (20 microM) and dibutyryl cAMP (1 mM) rapidly increased cytosolic free Ca2+ both in the presence and absence of extracellular Ca2+. More than 80% of the overall increase in cytosolic free-Ca2+ levels could be accounted for by the mobilization of intracellular Ca2+ stores. Somatostatin effectively blocked the forskolin effect (32% inhibition) but not the dibutyryl cAMP-induced effect. Somatostatin appears to inhibit secretagogue-induced increases in cytosolic free [Ca2+] by interfering with cAMP production and probably with Ca2+ transport across the cell membrane. PMID- 2883057 TI - Pancreatic somatostatin is a mediator of glucagon inhibition by hyperglycemia. AB - We have previously shown that a nonimmunoreactive analogue of somatostatin, (D Ala5, D-Trp8)-somatostatin, differentially inhibits pancreatic somatostatin secretion without inhibiting insulin or glucagon secretion. During normoglycemia, suppression of pancreatic somatostatin with this analogue increases glucagon and insulin secretion, suggesting that pancreatic somatostatin tonically inhibits glucagon and insulin secretion by a paracrine mechanism. In our study, we used this analogue to determine whether endogenous pancreatic somatostatin has a role in the inhibition of glucagon secretion by hyperglycemia. The experiments were performed in pentobarbital-anesthetized, laparotomized dogs. To measure the pancreatic output of somatostatin directly, pancreatic venous blood was sampled from the right lobe of the dog pancreas, and the pancreatic blood flow was measured. In the first set of experiments, glucagon secretion was suppressed by a glucose infusion (200 mg/kg bolus and 20 mg X kg-1 X min-1 i.v.) for 3 h. Plasma glucose rose from 102 +/- 6 to 365 +/- 34 mg/dl. Pancreatic insulin output increased 10-fold, pancreatic somatostatin output increased from 1.2 +/- 0.3 to 3.0 +/- 0.8 ng/min, and pancreatic glucagon output was suppressed from 1.4 +/- 0.7 to 0.5 +/- 0.1 ng/min. After 2 h of glucose infusion, an infusion of the analogue (5.5 micrograms/min i.v.) reversed both the stimulation of somatostatin and the suppression of glucagon without significantly changing either the plasma glucose level or the pancreatic insulin output. In a second set of experiments, basal somatostatin output was suppressed by the analogue (5.5 micrograms/min i.v.) for 15 min before the administration of glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883058 TI - Somatostatin impairs clearance of exogenous insulin in humans. AB - Somatostatin has been widely used to suppress endogenous pancreatic hormone secretion in research studies. Many of these studies required the simultaneous infusion of a hormone together with somatostatin. A critical assumption for its use in metabolic investigation is that somatostatin has no effect on the action or clearance of a concomitantly infused hormone. To test whether clearance of an exogenously infused hormone is affected, we infused insulin with or without somatostatin in two sets of studies. Insulin (40 mU X kg-1 X h-1) was infused for 100 min (n = 6). Plasma glucose levels fell to 55 +/- 4.1 mg/dl with insulin alone and significantly lower, to 44 +/- 1.9 mg/dl, when somatostatin (250 micrograms/h) was also infused (P less than .01). Plasma immunoreactive insulin (IRI) rose to 57 +/- 12.5 microU/ml with insulin alone, which was significantly different from 88 +/- 15 microU/ml when insulin was infused together with somatostatin (P less than .01). When a smaller dose of insulin (30 mU X kg-1 X h 1) was infused for 100 min (n = 4), similar results were observed. When somatostatin was infused together with insulin, plasma glucose fell to lower levels (41 +/- 4.2 vs. 62 +/- 9.5 mg/dl; P less than .01) and plasma IRI rose higher (39 +/- 8.5 vs. 27 +/- 5.9 microU/ml; P less than .01) than when insulin was infused alone. C-peptide was equally suppressed by hypoglycemia regardless of whether somatostatin was administered, indicating suppression of endogenous insulin during these studies. We conclude that somatostatin infusion impairs the clearance of exogenous insulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883059 TI - Effect of a long-acting somatostatin analogue (SMS 201-995) on postprandial gastric emptying of 99mTc-tin colloid and mouth-to-caecum transit time in man. AB - The effect on gut motility of a single subcutaneous injection of 50 micrograms of the long-acting somatostatin analogue, SMS 201-995, was investigated in 8 normal volunteers who took a drink containing 99mTc and lactulose with a mixed meal. The rate of gastric emptying was assessed by disappearance of the isotope from the stomach area as measured by a gamma camera, and mouth-to-caecum transit time (MCTT) was measured by the appearance of hydrogen in the breath. Gastric emptying was accelerated, with a significant reduction of the time taken to 50% isotope disappearance (37.2 +/- 3.3 min during control study vs 23.3 +/- 3.4 min after SMS injection; p less than 0.01). In contrast, MCTT was prolonged from 57.3 +/- 9.4 min (control) to 203.6 +/- 14.7 min after SMS (p less than 0.001). PMID- 2883060 TI - Effect of the somatostatin analogue sandostatin (SMS 201-995) on gastrointestinal, pancreatic and biliary function and hormone release in normal men. AB - The effect of the long-acting somatostatin analogue Sandostatin (SMS 201-995) on intestinal absorption and propagation (mouth-to-caecum transit time; MCTT), on pancreatic secretion and on gall bladder contraction after direct (secretin pancreozymin test) and indirect stimulation (Lundh meal), and on meal-induced responses of seven gastrointestinal regulatory peptides has been investigated. In a double-blind cross-over study, 9 healthy volunteers completed two 7-day periods with subcutaneous injections of either placebo or 25 micrograms SMS 201-995 twice daily. Mean faecal fat excretion was increased to 19.2 g/day and MCTT was three times longer during the SMS period. After duodenal infusion of a mixture containing D-galactose, D-xylose and triglycerides, SMS 201-995 significantly reduced the serum concentrations of D-galactose but increased serum levels of D xylose. After 6 days of pretreatment, SMS 201-995 completely suppressed duodenal trypsin, lipase and bilirubin increases in response to endogenous stimulation by a Lundh meal. Concomitantly, cholecystokinin (CCK) release and gall bladder contraction were almost abolished. Compared with placebo, SMS 201-995 significantly diminished pancreatic amylase, trypsin and lipase output after stimulation with CCK, while the secretion of fluid and bicarbonate in response to secretin was unchanged. This inhibition of enzyme response was significantly more marked after a single injection of the analogue than after pretreatment for 7 days and did not reach the level of exocrine pancreatic insufficiency. CCK induced gall bladder contraction was significantly inhibited by a single dose of 25 micrograms SMS 201-995 but not after 7 days of pretreatment with the somatostatin analogue. PMID- 2883062 TI - A survey of new users of psychotropic drugs in Australian general practice. AB - During 1984 and 1985, a study was conducted of 104 new adult users of benzodiazepines or antidepressants prescribed by sixty-two general practitioners in Sydney, Australia. New users of antidepressants tended to be older than new users of benzodiazepines. Seventy per cent of new users of psychotropic drugs were women and 67% were suffering significant psychological distress according to the 12-item general health questionnaire administered in a home interview. It was estimated that the general practitioners initiated approximately one new episode of use per week, and that repeat prescriptions constituted the bulk of general practitioner prescribing of these drugs. PMID- 2883061 TI - Neuropeptidergic versus cholinergic and adrenergic regulation of islet hormone secretion. PMID- 2883063 TI - [The role of Italian cardiology in the Italian Group for the Study of Streptokinase in Myocardial Infarct. Distribution, structural and organizational characteristics of coronary intensive care units]. AB - After a short "historical" mention of the fundamental stages that produced the protocol and the beginning of the G.I.S.S.I. study, we examine the statistics on the organizing, epidemiological and therapeutic aspects observed during the G.I.S.S.I. study. Even if the collected data are referred only to the 176 CCU participating in the G.I.S.S.I., and the results on mortality and hospitalization time takes into account only the myocardial infarctions randomized for the study, and the criteria used in the analysis (organizational and structural parameters) are considered arbitrary, we underline the evident lack of balance in the geographic distribution of the CCU; this imbalance involves also the instrumental equipment. Furthermore we note a poor, but significative, decrease in the mortality of the Units with a higher hospitalization/year and with a more sophisticated instrumental equipment. Another interesting data, from a clinical and organizational point of view, concerns the high number of patients--10210 out of 20020 (51%)--excluded from the randomization, because hospitalized after 12 hours. This data underlines the big problem of the "pre-coronary" time, which is still to long, actually, in our country. These data must induce to increase the efforts to develop the network of CCU in our Country and to inform the people and the sanitary operators about the usefulness of quicker therapeutic intervention. From an epidemiological investigation, the best results were obtained in the patients hospitalized within the first few hours from the onset of the symptoms. PMID- 2883064 TI - Effects of hexamethonium and atropine on the basal levels of immunoreactive vasoactive intestinal polypeptide in dogs. AB - The basal levels of immunoreactive vasoactive intestinal polypeptide (IR-VIP) in veins of the gastrointestinal tract and the effect of hexamethonium and atropine on basal levels of IR-VIP were examined in anesthetized dogs. The basal mean plasma IR-VIP levels in the pancreaticoduodenal vein, the mesenteric vein of the jejunum, the mesenteric vein of the ileum and the right colonic vein, but not the left gastroepiploic vein, were significantly higher than those in the femoral vein. These basal levels of IR-VIP were decreased by atropine, but not by hexamethonium. Thus, the main source of basal VIP in the portal vein is probably the duodenum (and pancreas) and the small and large intestine, and the basal levels of VIP are under the control of muscarinic receptors, in canine gastrointestinal tract. PMID- 2883066 TI - Divergent effects of bombesin and bethanechol on stimulated gastric secretion in duodenal ulcer and in normal men. AB - To further investigate differences in the responses of normals and patients with duodenal ulcer with respect to gastrin release and acid and pepsin secretion, we infused bombesin (1 microgram/kg X h) or bethanechol (40 micrograms/kg X h) during the middle hour of a 3-h infusion of pentagastrin and compared the results with a pentagastrin infusion without added drug. Pentagastrin dosage (0.1 microgram/kg X h) was set to give about half-maximal response, to detect either inhibition or further stimulation of gastric secretion, whereas the dose of bombesin was chosen to give maximal gastrin but less than maximal acid secretion. Serum gastrin and somatostatin were also measured. In all subjects tested, bethanechol produced no effects on acid, gastrin, or somatostatin release but increased pepsin output. By contrast, bombesin inhibited pentagastrin-stimulated acid output in all 6 normal men by an average of 55%, whereas it inhibited acid output in only 2 of the 9 men with duodenal ulcer. Serum gastrin increases after bombesin in duodenal ulcer were three to four times greater than in normals. Although bombesin stimulates acid only by releasing gastrin, we postulate that bombesin may also simultaneously limit acid and pepsin secretion and speculate that this effect could be mediated by bombesin-induced somatostatin release. The cause for differences between duodenal ulcer and normal remain speculative. PMID- 2883065 TI - The association of pyoderma gangrenosum with ulcerative colitis in Japan. AB - A patient with pyoderma gangrenosum (PG) and ulcerative colitis (UC) is described. He had melena and systemic skin lesions. The skin lesions consisted of small discrete ulcers on the back and head and large punched-out ulcers on the legs. He was successfully treated with prednisolone and salazosulfapyridine. He became asymptomatic after two weeks' treatment. Although the association of PG with UC is well documented among Caucasians, it is very rare among Japanese. PMID- 2883067 TI - Actions of sulfasalazine and 5-aminosalicylic acid as reactive oxygen scavengers in the suppression of bile acid-induced increases in colonic epithelial cell loss and proliferative activity. AB - Sulfasalazine suppresses mucosal injury in patients with ulcerative colitis, but the mechanism of its therapeutic action is uncertain. In the present study, we examined the mechanism of the protective action of sulfasalazine in a rat model in which colonic epithelial cell loss and subsequent increases in epithelial proliferative activity were induced by intracolonic instillation of sodium deoxycholate. Sulfasalazine or its therapeutically active metabolite 5 aminosalicylic acid suppressed the loss of deoxyribonucleic acid into the colonic lumen and the subsequent increases in mucosal ornithine decarboxylase activity and tritiated thymidine incorporation into deoxyribonucleic acid induced by sodium deoxycholate. Sulfasalazine and 5-aminosalicylic acid also blocked xanthine-xanthine oxidase-induced loss of deoxyribonucleic acid and the subsequent proliferative response. In vitro sodium deoxycholate increased reactive oxygen formation by colonic mucosal scrapings or isolated crypt epithelium. These actions of sodium deoxycholate on reactive oxygen formation were blocked by sulfasalazine or 5-aminosalicylic acid. Sulfapyridine, a therapeutically inactive metabolite of sulfasalazine, had no effect on sodium deoxycholate-induced increases in surface cell sloughing, ornithine decarboxylase, tritiated thymidine incorporation into deoxyribonucleic acid, chemiluminescence, or superoxide production. The ability of sulfasalazine and 5 aminosalicylic acid to scavenge reactive oxygen may play a role in their therapeutic effects of inflammatory bowel disease. PMID- 2883068 TI - Erosive gastritis and gastrointestinal bleeding in a female runner. Prevention of the bleeding and healing of the gastritis with H2-receptor antagonists. AB - A 33-yr-old female runner presented with upper gastrointestinal symptoms and iron deficiency anemia. She was found to have erosive gastritis that was present when she exercised and which was associated with symptoms. Gastrointestinal blood loss during exercise periods was confirmed by measuring fecal blood loss using 51Cr labeled red cells. Symptoms, gastritis, and blood loss disappeared with cessation of running or with H2-receptor antagonist therapy. PMID- 2883069 TI - Histological and immunohistochemical study on ontogeny of the endocrine cells in the quail gizzard. AB - The pre- and post-hatching development and differentiation of the endocrine cells in quail gizzard were examined histologically and immunohistochemically. A total of 158 heads (from 5th d of incubation to adult) were used in this study. The formation of gizzard tubular glands began from 11th d of incubation. 8 kinds of endocrine cells, argyrophil cells, and gastrin releasing polypeptide (GRP)-, 5 hydroxytryptamine (5-HT)-, somatostatin-, glucagon-, avian pancreatic polypeptide (APP)-, neurotensin-, and gastrin-immunoreactive cells were detected in the gizzard. These endocrine cells began to appear from 10th d of incubation. Argyrophil cells and GRP-immunoreactive cells in the gizzard were increased with age. Other kinds of immunoreactive cells were found rarely and irregularly, and some of them were found transitory in the embryonic stage. PMID- 2883070 TI - Flunarizine and alpha-adrenergic responses in isolated canine saphenous veins. AB - Experiments were designed to determine how flunarizine affects contractions of cutaneous veins to alpha-adrenergic activation. Rings of canine saphenous vein were mounted at optimal length for isometric tension recording in organ chambers filled with physiological salt solution. At concentrations higher than those needed to inhibit KCl-induced contractions, flunarizine inhibited the contractile responses evoked by alpha 2-adrenergic agonists (B-HT 920, xylazine), partial (St 587) and full (cirazoline, phenylephrine) alpha 1-adrenergic agonists and the combined alpha 1-/alpha 2-adrenergic agonist, norepinephrine. The inhibitory effect of flunarizine against alpha 2-adrenergic responses was similar to that produced by other calcium-antagonists and results presumably from inhibition of the influx of extracellular calcium. The inhibitory effect of flunarizine against alpha 1-adrenergic responses was greater than expected and appears to result from competitive antagonism of alpha 1-adrenoceptors (pA2 = 5.79). Therefore, flunarizine can decrease adrenergic contractile responses by depressing the influx of extracellular calcium and by blocking postjunctional alpha 1 adrenoceptors. PMID- 2883071 TI - Adrenergic agonists do not compete with the antagonist (-)3 [125I]iodocyanopindolol for binding to rat pleural or peritoneal mast cell adrenergic receptor. AB - (-)3-[125I]iodocyanopindolol (ICYP), a high selective, high specific beta antagonist is employed to characterize beta-adrenoceptors on rat pleural and peritoneal mast cell populations. Results show that non specific binding is low, and that pleural mast cells exhibit greater number of receptors per cell (140,000) than peritoneal cells (90,000). Dissociation constants (Kd) are 0.37 +/ 0.01 and 0.55 +/- 0.02 nM for pleural and peritoneal cells, respectively. Competition experiments show that isoproterenol do not displaces ICYP neither in pleural nor in peritoneal cells. Low concentrations of propranolol displace ICYP from its binding sites, but atenolol does not. Results point to the existence in mast cells of mainly atypical. beta 2-receptors, since the agonist isoproterenol does not compete with the antagonist ICYP. PMID- 2883072 TI - The effects of chronic treatment with fencamfamine on body weight, food intake and stereotyped behaviour in rats. AB - The effects of chronic treatment with fencamfamine (10.0 mg/kg, i.p.) or saline were studied in rats. Chronic fencamfamine treatment reduced body weight of rats below their normal body weight. Thereafter, weight increased, in parallel to that of control rats. There was an increasing trend in food intake in both groups and a reduction was observed in food intake on the first seven days of fencamfamine treated rats. Fencamfamine repeated administration enhanced stereotyped sniffing while rearing behaviour gradually declined until 25 days. However, the same treatment did not interfere with the intensity of stereotypy. These findings suggest the need for a re-evaluation of current concept in the tolerance to the effects of fencamfamine and other stimulant drugs. PMID- 2883073 TI - On the presence of opioid receptors in guinea-pig ventricular tissue. AB - The cardiac response to sympathetic nerve stimulation, induced by trains of field pulses, was studied in isolated guinea-pig ventricular strips. Dynorphin-(1-13) and [D-Ala2, D-Leu5]enkephalinamide, but not morphine, reduced, in a dose dependent manner, the cardiac sympathetic response. The effect of the two opioid peptides was antagonized by naloxone. The opioid agonists did not affect the response to exogenous noradrenaline. Neither naloxone nor a mixture of peptidase inhibitors modified the cardiac response to sympathetic nerve stimulation. PMID- 2883074 TI - Glutathione metabolizing enzyme activities in human thyroid. AB - Glutathione peroxidases, glutathione transferase, glutathione reductase and gamma glutamyl transpeptidase activities were analyzed in human thyroid tissues obtained from 17 patients undergoing resectional surgery because of a malignancy. It was deduced, from measurements of glutathione peroxidase activity with both H202 and cumene hydroperoxide, that thyroid contains only the selenium enzyme. The absence of selenium independent glutathione peroxidase activity in thyroid was confirmed with gel filtration experiments. An interindividual variation of about 28-fold was found measuring glutathione transferase activity with 1-chloro 2,4-dinitrobenzene. Subjecting a fraction of human thyroid cytosols partially purified by G-100 Sephadex column to isoelectricfocusing run, a single peak of glutathione transferase activity centered at pH 4.6 was obtained. An adequate level of glutathione reductase and gamma-glutamyl transpeptidase activities was also found in all specimens investigated. PMID- 2883075 TI - Disequilibrium on human chromosome 11p. PMID- 2883076 TI - Sex differences in recombination fraction estimates and their effect on ordering of chromosome 11 markers. PMID- 2883077 TI - Linkage analysis between Huntington disease and the G8 marker locus. PMID- 2883078 TI - Strategies for efficient linkage analysis: example of Huntington's disease pedigrees. PMID- 2883079 TI - Analysis of Huntington disease linkage to G8. PMID- 2883080 TI - Effect of age-at-onset specifications on Huntington disease--G8 linkage analysis. PMID- 2883082 TI - Linkage studies and prediction of risks for Huntington disease. PMID- 2883081 TI - Analysis of Huntington disease linkage and age-of-onset distributions. PMID- 2883083 TI - Linkage analysis of G8 and Huntington's disease. PMID- 2883084 TI - Report on genetic linkage analysis between Huntington's disease and the G8 DNA polymorphism. PMID- 2883085 TI - Seizures with neuroleptics and antidepressants. AB - Seizures remain among the most serious side effects of psychotropic drugs. The authors review the literature associating neuroleptic and antidepressant medications with seizures, discussing the relative "seizurogenicity" of different medications, risk factors for seizures, and drugs of choice for high-risk patients. Case histories are presented. Available evidence suggests that molindone, fluphenazine, and haloperidol are among the least seizurogenic neuroleptics and that doxepin, monoamine oxidase inhibitors, or electroconvulsive therapy may be safest in treating the depressed patient at risk for seizures. PMID- 2883086 TI - Analysis of the human apolipoprotein B gene; complete structure of the B-74 region. AB - In this paper we describe the nucleotide sequence of the B-74 region of human apolipoprotein B-100 mRNA. This region comprises the 3'-proximal three-quarters of the mRNA and contains 10,089 nucleotides (nt), 9786 of which are coding. Combining our data with the published sequence of the 5'-proximal one-quarter (i.e., the B-26 region [Protter et al., Proc. Natl. Acad. Sci. USA 83 (1986) 5678 5682] assigns 14,059 nt to the apoB-100 mRNA. The coding sequence spans 13,548 nt or 4516 amino acids (leader peptide excluded). The B-74 part of the apoB gene is built up of five exons separated by small introns, and is dominated by an unusually large exon of 7.5 kb. The derivation of two (EcoRI and XbaI) restriction fragment length polymorphisms occurring in the coding region is discussed. PMID- 2883087 TI - Organization of genes expressing the blood-group-M-specific hemagglutinin of Escherichia coli: identification and nucleotide sequence of the M-agglutinin subunit gene. AB - The organization of genes encoding the blood group M-specific hemagglutinin (M agglutinin) of Escherichia coli strain IH11165 was studied with a cloned 6.5-kb DNA segment. This DNA segment contains at least five genes which code for the polypeptides of 12.5, 30, 80, 18.5 and 21 kDa. The 30-, 80- and 21-kDa polypeptides are synthesized as precursors that are approximately 2 kDa larger. The 21-kDa polypeptide was identified as the M-agglutinin subunit by its reactivity with anti-M-agglutinin serum. Nucleotide sequence analysis of the corresponding gene showed that the M-agglutinin precursor had a 24-amino acid (aa) signal sequence, while the mature protein is 146 aa residues long. Although the organization of the M-agglutinin gene cluster resembles those of other E. coli adhesins, there is no significant sequence homology between the M-agglutinin subunit and the subunits of the other potentially related proteins in E. coli. PMID- 2883088 TI - Optimal pain control in elderly cancer patients. AB - The optimal management of pain in the elderly cancer patient is founded on astute assessment of pain and other symptoms, development of a pain diagnosis derived from the clinical evaluation, treatment of underlying causes where possible, and the expert application of analgesic techniques. Analgesic techniques themselves are multimodal. Pharmacologic approaches are the mainstay, but an individual patient may benefit from the use of anesthetic, neuroaugmentative, surgical, physiatric, or psychological methods, as well. Guidelines for the assessment and integrated management of these patients are suggested, with specific emphasis on the use of pharmacologic therapy. PMID- 2883089 TI - Effects of buphenine (nylidrin) on the perfused mammalian eye. AB - Buphenine (nylidrin), a beta-adrenergic agonist, is used therapeutically for its vasodilating effect on the peripheral circulation and possibly on the cerebral circulation as well. In spite of its ophthalmic usage in degenerative retinal disease and glaucoma, buphenine's ocular effects and their mechanisms are not sufficiently established. Consequently, we studied the action of 4.5-120 microM buphenine in isolated, arterially perfused cat eyes, and then used light-evoked electrical signals, perfusion flow rates and the diameters of the retinal vessels as parameters for the drug's effect. Our findings showed that buphenine induced a marked, dose-related, reversible increase in the amplitude of the electroretinogram (ERG) b-wave, a decrease in the c-wave, but no significant changes in the standing potential and light peak of the DC-ERG. The compound action potential of the optic nerve revealed dose-dependent and reversible changes in configuration. However, the flow of perfusate was not affected by the drug, and the diameter of retinal vessels did not change significantly. Our studies suggest that the interaction of buphenine with retinal adrenergic receptors is not related to the vasculature present but to elements involved in information processing. It is likely that these receptors are linked to neurons, since the beta-agonist affected the ERG b-waves as well as the compound action potential of the optic nerve. PMID- 2883090 TI - [Occupational hygiene in agriculture in the 11th Five-Year Plan and its objectives in the light of resolutions of the 27th Congress of the CPSU]. PMID- 2883091 TI - [Evaluation of the inhibitory effect on uterine contraction of the preparation fenoterol produced by Polfa and a comparison of its effect with that of partusisten]. PMID- 2883092 TI - [Retrograde or orthograde anatomic perfusion of the free forearm flap?]. AB - The free forearm flap is ideal for vascularized tissue transfer because of its large vessels and multiple nerve supply. In the case presented a distally based forearm flap on a long vascular pedicle was employed relying on a reversed blood flow. Unfortunately the reversed venous flow did not develop and therefore in order to provide a venous drainage an autologous vein graft was used. PMID- 2883093 TI - [The mode of anti-inflammatory action of a topical non-steroidal anti inflammatory drug, etofenamate]. AB - In order to ascertain the mode of anti-inflammatory action of a topical non steroidal anti-inflammatory drug, etofenamate which is a diethylene glycol ester of flufenamic acid, the in vitro test for the mechanism of the action were carried out. Etofenamate (3 microM) was hydrolysed to flufenamic acid at a rate of 39.5% and 57.0% of the dose during 30 and 60 min incubation, respectively, when incubated with rat peritoneal macrophages stimulated with starch and bacto peptone in phosphate-buffered saline. PGE2 generation by these cells in MEM medium was dose-relatedly inhibited with etofenamate as well as flufenamic acid at the dosage range of 1 to 30 microM. This suggests that unchanged etofenamate is active, since the highest conversion rate of etofenamate to flufenamic acid was 15% of the dose during the incubation. Etofenamate produced a dose-related inhibition against lipoxygenase prepared from peritoneal polymorphonuclear leucocytes of guinea pigs, and its activity (IC50 = 5.3 X 10(-5) M) was stronger than that of caffeic acid; flufenamic acid was inactive. Inhibitory activity of etofenamate was one-third or less that of flufenamic acid against the hypotonic hyperthermic lysis of rat erythrocytes and heat-denaturation of bovine serum albumin. From these results, it was suggested that topically applied etofenamate produces its anti-inflammatory action through prostaglandin synthesis inhibition by flufenamic acid produced in the inflammatory tissue and inhibition of prostaglandin synthesis by macrophages and lipoxygenase inhibition by unchanged etofenamate. PMID- 2883094 TI - [Anti-allergic effects of 1-(2-ethoxyethyl)-2-(4-methyl-1 homopiperazinyl)benzimidazole fumarate (KB-2413)]. AB - The effects of KB-2413 on four types of allergic reactions classified by Coombs and Gell were investigated. KB-2413 inhibited homologous passive cutaneous anaphylaxis and passive anaphylactic bronchoconstriction in guinea pigs mediated by IgE-like antibody, and ED50 values were 0.0017 mg/kg, p.o., and 0.022 mg/kg, p.o., respectively. KB-2413 also inhibited IgG-mediated anaphylactic bronchoconstriction in guinea pigs actively sensitized with egg albumin. Both complement-dependent immune hemolysis and complement-independent hypotonic hemolysis were inhibited by KB-2413 in a concentration-dependent manner. KB-2413 had no effect on the Forssman systemic reaction. The passive Arthus reaction in guinea pigs sensitized with anti-egg albumin rabbit serum was unaffected by KB 2413. However, the early stage of the active Arthus reaction in rabbits sensitized with egg albumin was inhibited. KB-2413 had an inhibitory effect on the efferent phase of delayed-type hypersensitivity induced by picryl chloride (PC-DTH) in mice. On the other hand, the afferent phase of PC-DTH in mice was unaffected. These results suggest that KB-2413 strongly suppresses type I allergic reactions, and it slightly suppresses type II, III and IV allergic reactions. PMID- 2883095 TI - [Do antacids with high acid-binding capacity modify mineral metabolism?]. PMID- 2883096 TI - [Aluminum concentration in the bones and brain following the administration of antacids]. PMID- 2883098 TI - [The aluminum problem in antacid therapy]. PMID- 2883099 TI - [Therapy using non-steroidal anti-inflammatory agents. New attempts at understanding the possible mechanisms of action]. PMID- 2883097 TI - [Aluminum--are all antacids really harmless?]. PMID- 2883100 TI - [Further perspectives on calcium antagonists]. PMID- 2883101 TI - Insulin, glucagon and somatostatin content in normal and diabetic duck pancreas. PMID- 2883102 TI - Ovarian cyclic GMP concentration and guanylate cyclase and cyclic GMP phosphodiesterase activities in proestrus rat after treatment with LH. PMID- 2883103 TI - Effects of ethanol and nicotine on gastrin and somatostatin release in rats. AB - An intravenous bolus injection of nicotine (1 mg/kg) markedly elevated gastric acid secretion; oral administration of ethanol (40%, 10 ml/kg) significantly increased arterial serum gastrin and somatostatin levels. Chronic pretreatment with oral nicotine (5 or 25 micrograms/ml in drinking tap water, for 10 days), but not acute pretreatment with a single oral dose of nicotine (2 or 4 mg/kg), inhibited the nicotine-induced gastric acid secretion and ethanol-induced gastrin and somatostatin release. Pretreatment subcutaneously with a ganglion-blocking dose of hexamethonium (10 mg/kg), however, inhibited nicotine-stimulated acid output and ethanol-evoked somatostatin secretion but not ethanol-induced gastrin release. It is concluded that ethanol-evoked gastrin secretion could be due to activation of specific sites which are not nicotinic receptors, but which are depressed by chronic nicotine pretreatment. On the other hand, the release of somatostatin by ethanol appears to be controlled by ganglionic receptors in the gut. PMID- 2883104 TI - Alpha 2-adrenoceptor agonists stimulate growth hormone secretion but have no acute effects on plasma cortisol under basal conditions. AB - Ten normal male subjects were administered clonidine (0.1 and 0.2 mg) or a highly selective alpha 2-adrenoceptor agonist S 3341 (1 and 2 mg) on separate occasions in a double-blind randomised placebo-controlled study; blood samples were obtained for measurement of serum GH and plasma cortisol via an indwelling venous cannula for 4 h after each drug administration. Both clonidine and S 3341 were equally effective at lowering supine, and particularly standing BP; both also caused mild sedation, although this was slightly less marked for S 3341. High doses of both clonidine and S 3341 significantly increased serum GH (peak increment after clonidine: 18.8 +/- 5.5 mU/l (mean +/- SEM); peak increment after S 3341: 21.1 +/- 4.8 mU/l). Neither drug affected plasma cortisol. It is concluded that GH release may be stimulated by alpha 2-adrenoceptor agonism. As S 3341 has slightly less central activity than clonidine at the doses employed, but is at least equally potent at stimulating GH release, it is probable that the alpha 2-adrenoceptor stimulation of GH release occurs outside the blood-brain barrier. The pituitary-adrenal axis appears resistant to manipulation of alpha 2 adrenoceptors under basal conditions. PMID- 2883105 TI - Further evidence for genetic heterogeneity in the fragile X syndrome. AB - The X-linked fragile X [fra(X)] syndrome, associated with a fragile site at Xq27.3, is the most common Mendelian inherited form of mental deficiency. Approximately 1 in 1060 males and 1 in 677 females carry the fra(X) chromosome. However, diagnosis of carrier status can be difficult since about 20% of males and 44% of females are nonpenetrant for mental impairment and/or expression of fra(X). We analyzed DNA from 327 individuals in 23 families segregating fra(X) for linkage to three flanking polymorphic probes: 52A, F9, and ST14. This allowed probable nonpenetrant, transmitting males and carrier females to be identified. A combined linkage analysis was conducted using these families and published probe information on F9 in 27 other families, 52A in six families, and ST14 in five families. The two-point recombination fraction for 52A-F9 was 0.13 (90% confidence interval, 0.10-0.16), for F9-fra(X) was 0.21 (0.17-0.24), and for fra(X)-ST14 was 0.12 (0.07-0.17). Tight linkage between F9 and fra(X) was observed in some families; in others loose linkage was seen suggesting genetic linkage heterogeneity. Risk analysis of carrier status using flanking DNA probes showed that probable nonpenetrant transmitting males were included in families showing both tight and loose linkage. Thus, in contrast to our previous conclusions, it appears that the presence or absence of nonpenetrant, transmitting males in a family is not an indicator of heterogeneity. To determine if heterogeneity was present, we employed the admixture test. Evidence for linkage heterogeneity between F9 and fra(X) was found, significant at P less than 0.0005. Nonsignificant heterogeneity was seen for 52A-F9 linkage. No heterogeneity was found for fra(X)-ST14. The frequency of fra(X) expression was significantly lower in families with tight F9-fra(X) linkage than in families with loose linkage. Cognition appeared to relate to linkage type: affected males in tight linkage families had higher IQs than those in loose linkage families. These findings of genetic heterogeneity can account in part for the high prevalence and apparent high new mutation rate of fra(X). They will affect genetic counseling using RFLPs. An understanding of the basis for genetic heterogeneity in fra(X) will help to clarify the nature of the unusual pattern of inheritance seen in this syndrome. PMID- 2883106 TI - Cystic fibrosis: typing 48 German families with linked DNA probes. AB - Two hundred and thirty five subjects from 48 German cystic fibrosis (CF) families were typed for restriction fragment length polymorphisms (RFLPs) detected by the probes pmet H, pmet D, and pJ 3.11, known to be tightly linked to the CF gene. Gene and haplotype frequencies suggest a linkage disequilibrium with the CF locus. The analysis of the predictive value of this typing in individual CF families indicates that the combined use of these probes provides a powerful diagnostic system both for carrier detection and prenatal diagnosis. In 33 out of 48 families carriers and non-carriers could be identified, and in 26 of these 33 families prenatal diagnosis could discriminate between affected and unaffected offspring. PMID- 2883107 TI - X-linked hypohidrotic ectodermal dysplasia: DNA probe linkage analysis and gene localization. AB - A linkage study of 24 families with hypohidrotic (anhidrotic) ectodermal dysplasia (HED) has been performed. The previously suggested linkage to DXYS1 has been confirmed, and linkage to probes DXS14 and DXS3 has been established. We suggest that the HED locus lies in the centromeric region between DXYS1 on the long arm and DXS14 on the short arm of the X chromosome, probably on proximal Xq. PMID- 2883108 TI - A DNA marker closely linked to the factor IX (haemophilia B) gene. AB - We have isolated a DNA segment, pX58dIIIc, from an X-chromosome library which identifies an SstI restriction fragment length polymorphism (RFLP) at locus DXS99. Linkage analysis in six informative families has shown that the DXS99 locus lies close to the factor IX gene (F9). No recombination was detected between these loci in 39 informative meioses (Z = 9.79, theta = 0.0). Therefore, DXS99 will be useful as a DNA marker for the assessment of carrier status in families with haemophilia B where intragenic markers are not informative. Heterozygosity at DXS99 is approximately 50% and, in conjunction with the RFLPs at F9, 90% of females at risk for being haemophilia B carriers should be diagnosed. PMID- 2883109 TI - Allele-specific DNA identity patterns. AB - A method of genetic analysis is presented which involves digestion of DNA with a single restriction enzyme (PvuII) and hybridisation with a mixture of five probes. Four of the five probes chosen recognise hypervariable regions (HVRs) of the human genome and hence an allele-specific DNA identity pattern results. An advantage of this approach to genetic characterisation is that the complex identity patterns may be broken down into simple allelic systems of known chromosomal localization by hybridisation with the individual probes. Also different probes may be included in a combined probe designed for particular types of investigation. PMID- 2883110 TI - Polymorphic DNA haplotypes at the human phenylalanine hydroxylase locus and their relationship with phenylketonuria. AB - Eight polymorphic restriction enzyme sites at the phenylalanine hydroxylase (PAH) locus were analyzed from the parental chromosomes in 33 Danish nuclear families with at least one phenylketonuric (PKU) child. Determination of haplotypes of 66 normal chromosomes and 66 chromosomes bearing mutant allele(s) demonstrated that there are at least two haplotypes which occur predominantly on PKU chromosomes and rarely otherwise. Overall, the relative frequencies of the various haplotypes are significantly different on PKU- and normal-allele bearing chromosomes, even though there is no predominantly occurring unique haplotype which can characterize the PKU chromosomes. In addition, no significant association (linkage disequilibrium) between any single polymorphic site and the mutant allele(s) was observed. The results suggest that either the phenylketonuric mutation was very ancient so that the polymorphic sites and the mutation have reached linkage equilibrium or the mutant allele(s) are the results of multiple mutations in the phenylalanine hydroxylase gene in man. Furthermore, a crude relationship between standardized linkage disequilibria and physical map distances of the polymorphic sites indicates that there is no apparent recombination hot-spot in the human phenylalanine hydroxylase gene, since the recombination rate within the locus appears to be uniform and likely to be occurring at a rate similar to that within the HLA gene cluster. The limitations of this later analysis are discussed in view of the sampling errors of disequilibrium measure used, and the potential utility of the PAH haplotypes for prenatal diagnosis and detection of PKU carriers is established. PMID- 2883111 TI - A hypervariable region at the D19S11 locus. AB - The polymorphic locus D19S11 consists of four closely linked RFLPs: alpha, beta, delta, and gamma on chromosome 19p13.2----19cen, revealed by subclones p13-1-82 and p13-2-21 from cosmid 1-13. Here, we report that p13-1-25, an additional subclone of c1-13, reveals three insertion/deletion RFLPs, alpha, epsilon, and phi, at the D19S11 locus. In situ hybridization of p13-1-25 to metaphase chromosomes from a carrier of a 19/X translocation with a breakpoint near the centromere confirms localization of D19S11 to 19p. Studies with hydatidiform moles have generated assignments of specific restriction fragments to these three loci, and genotypic studies in three-generation families have indicated that they are closely linked. Loci alpha (also detected by p13-1-82) and phi each have but two common alleles, whereas epsilon has at least 33 alleles, including a null allele. Fifty unrelated individuals tested displayed unique fragment patterns on Taq I blots probed with p13-1-25. Applications of this probe include monitoring loss of chromosome 19 during tumorigenesis, monitoring engraftment of donor bone marrow after transplantation, testing for paternity, and mapping disease genes on chromosome 19. PMID- 2883113 TI - DNA polymorphisms associated with HLA-B-like genes and evidence for a duplication of B40 genes detected with an HLA-B-specific DNA probe. AB - Analysis of polymorphic DNA endonuclease restriction fragments by Southern blotting indicates that the genetic complexity of the HLA class I gene family is larger than the complexity indicated by serologically defined HLA-A, -B and -C gene products (Orr et al., 1982). There are correlations between polymorphic restriction endonuclease fragments in a limited number of HLA class I alleles; in fact, a few alleles in the population have been correlated with the presence of polymorphic DNA fragments (Cann et al., 1983; Cohen et al., 1983; Orr & De Mars, 1983; Lucotte, Coulondre & Salmon, 1985; Driesel et al., 1985). Recently, probes shown to be specific for HLA-A and HLA-B genes (Grumet et al., 1983; Koller et al., 1985) were constructed from the 3'-untranslated region of these genes. PMID- 2883112 TI - X-linked immunodeficiency with hyperimmunoglobulinemia M appears to be linked to the DXS42 restriction fragment length polymorphism locus. AB - The gene involved in X-linked immunodeficiency with hyperimmunoglobulinemia M (XHM) was localized by the use of nine restriction fragment length polymorphic (RFLP) markers covering the entire X chromosome. Multipoint linkage analysis of RFLP data obtained in a three generation XHM pedigree indicates the Xq24-q27 area around the DXS42 RFLP locus as the most likely localization of the XHM locus. PMID- 2883114 TI - Molecular mapping of crossover sites within the I region of the mouse MHC. Analysis of ten recombinant chromosomes. PMID- 2883116 TI - Heterogeneity of human C4 gene size. A large intron (6.5 kb) is present in all C4A genes and some C4B genes. AB - In this article we present a study showing that the human C4 genes differ in length because of the presence or absence of a 6.5 kb intron near the 5' end of the gene. DNA from individuals of known HLA, factor B, and C4 haplotypes was analyzed for restriction fragment length polymorphism (RFLP) by Southern blot analysis with C4-specific cDNA probes. The RFLP patterns obtained showed that the C4 genes are either 22.5 kb or 16 kb in length. They are referred to as long and short C4 genes, respectively. A population study was carried out to examine the distribution of the gene size according to C4 allotypes and haplotypes. Long C4 genes included all C4A genes studied and also some C4B allotypes, e.g., B1 on most C4 A3B1 haplotypes. Similarly, C4B null genes were found to be of the long form. Other C4B allotypes tested were found to be coded for by short C4 genes, including B2, B1 in C4 A6B1 and C4 AQOB1 (with a single C4B gene haplotype). PMID- 2883117 TI - Identification of flaviviruses by the single-radial-haemolysis test. PMID- 2883115 TI - DNA polymorphism of MHC III genes in inbred and wild mouse strains. AB - Genes encoding the second component (C2), factor B, and complement protein C4 and Slp (sex-limited protein) are members of the major histocompatibility complex class III gene cluster. In this report we describe isolation of a mouse C2 cDNA clone and its use together with factor B and C4 cDNA clones to examine the S region in a panel of 42 haplotypes in laboratory and wild mice representing 5 species and subspecies of Mus. Conservation of the C2 factor B gene duplex was evidenced by relatively limited polymorphism associated with speciation and nucleotide sequence homology between mouse and human C2 and factor B. The C4-Slp gene duplex, on the other hand, showed extensive polymorphism by DNA blot analysis. This polymorphism correlated poorly with the C2/factor B restriction fragment length polymorphism, suggesting independent evolution of these two segments of the S region. Taken together, these data will be of particular importance in studies of mouse strains with abnormal regulation of immune effector systems since the class III gene products are essential for activation of the complement cascade. PMID- 2883118 TI - Susceptibility of mosquito larvae to Leptolegnia sp. PMID- 2883119 TI - Mapping of the mouse atrial natriuretic factor gene. Evidence for tight linkage to the Fv-1 locus. AB - The importance of atrial natriuretic factor (ANF) in the regulation of salt balance and blood pressure is now widely recognized, and it would be extremely informative for both physiologists and molecular biologists to have mutants available that exhibit abnormal expression of this peptide hormone. The most direct mutation would affect the structural gene itself by altering either its coding potential or its regulation. With this aim in mind, it is of considerable interest to accurately determine the chromosomal position of the ANF gene (Anf) in the mouse. This information would permit a comparison with known mutations and provide a means of screening for mutations at this locus. Using recombinant inbred mouse strains, we undertook the mapping of the mouse Anf gene and demonstrated linkage of the gene to the Friend virus susceptibility-1 (Fv-1) locus on chromosome 4. The mapping was performed using a restriction fragment length polymorphism extant between the two parental strains. No recombination event between Anf and the Fv-1 locus was evident in any of the 34 strains tested. The assignment of Anf to this region of chromosome 4 coincides with the reported position of the cribriform degeneration mutation, which includes in its phenotype an abnormal electrolyte distribution. We have, therefore, begun studying this mutation to determine whether a defect in ANF expression is the underlying cause of the phenotype. Thus far, we have found no major DNA rearrangement close to the Anf gene. PMID- 2883120 TI - The role of adrenergic mechanism in tremorine-induced tremors in rats: antitremor effect of beta-adrenoceptor antagonists. AB - Tranylcypromine (TCP) pretreatment was found to accelerate the tremorogenic activity of tremorine in rats. Conversely, reserpinization delayed the onset of induction of tremors, and a significant diminution in their intensity was observed in these rats. A comparative study of the antitremor activity of beta adrenoceptor antagonists against this tremor-model showed that butoxamine (beta 2 antagonist) and propranolol (nonselective antagonist) were able to afford a rapid and powerful protection, whereas a weaker and delayed effect was observed in rats treated with the beta 1-antagonist, acebutolol. Furthermore, the antitremor activity of butoxamine and propranolol but not that of acebutolol was found to be potentiated and diminished in rats pretreated with reserpine and TCP, respectively. It was inferred that beta 2-receptor modulated the tremorogenic activity of tremorine, and that inhibition by propranolol or butoxamine of this subtype beta-adrenoceptor resulted in rapid and powerful suppression of tremors, and that the antiadrenergic activity of acebutolol was unlikely to have a role in its antitremor effect. PMID- 2883121 TI - Immune-complex-induced inflammatory reaction studied by intravital microscopy: role of histamine and arachidonic acid metabolites. AB - An immune-complex-induced inflammatory reaction was elicited in the hamster cheek pouch microvasculature of ovalbumin (OA)-immunized animals by exposure to 1 or 100 micrograms/ml OA. The low antigen dose caused arteriolar constriction, transient platelet aggregation, and a reversible increase in vascular leakage at postcapillary venules. With the high antigen dose, the constriction and platelet aggregation were more pronounced and the vascular leakage was prolonged. This antigen dose also caused a massive PMNL accumulation in small venules, which coincided with the prolonged vascular leakage. Histamine was released in the reaction as pretreatment with mepyramine largely inhibited the leakage response to 1 microgram/ml OA. With 100 micrograms/ml OA, only the initial phase of vascular leakage was inhibited by mepyramine, leaving the prolonged vascular leakage and PMNL accumulation unaltered. Pretreatment with methylprednisolone 16 18 h prior to the experiments reduced both phases of vascular leakage as well as the PMNL accumulation. Pretreatment with the combined cyclo- and lipoxygenase inhibitors BW755C or nordihydroguaiaretic acid (NDGA) reduced the initial vasoconstriction induced with 100 micrograms/ml OA, thereby augmenting the initial vascular leakage. Despite this, the prolonged phase of vascular leakage was reduced in the NDGA-treated animals. Cyclooxygenase products were not found to play a crucial role in mediating the vascular response; on the contrary, indomethacin pretreatment slightly potentiated the vascular leakage induced by the low antigen dose. PMID- 2883123 TI - Pilus-mediated binding of bovine enterotoxigenic Escherichia coli to calf small intestinal mucins. AB - In this study we show that the adhesion to mucus of the enterotoxigenic Escherichia coli strains responsible for diarrhea in calves involves a bacterium mucin recognition phenomenon in which the bacterial pili and specific mucus receptors carried by the glycoproteins (2,000 to 400 kilodalton) play a major role. An adhesion maximum was observed at a pH of less than 6 (4.75 to 5.25). The sialic acids and galactose appeared to be at least partly responsible for the attachment of K99 pili, whereas F41 pili preferentially recognized desialylated receptors. The attachment of different strains of E. coli characterized by the presence of the three main pili, K99, F41, and FY, known to be responsible for the binding of enterotoxigenic E. coli to the intestinal epithelium of the calf, was studied using Scatchard and Hill analyses. The attachment mechanism of bacteria carrying K99 pili showed positive cooperativity. FY and F41 pili recognized independent receptor sites, the first on sialylated mucus and the second on sialidase-treated mucus. Moreover, F41 pili were found to bind the native mucus according to a negative cooperativity phenomenon. Finally, the recognition sites carried by bacterial pilins may be saturated by some animal glycoprotein glycans which are therefore adhesion inhibitors. PMID- 2883122 TI - Purification, morphology, and genetics of a new fimbrial putative colonization factor of enterotoxigenic Escherichia coli O159:H4. AB - The ability to colonize the small intestine is essential for the pathogenesis of diarrhea caused by enterotoxigenic Escherichia coli (ETEC). Colonization is mediated by fimbriae (pili), of which there are several antigenically distinct types, including colonization factor antigen I, colonization factor antigen II (CS1, CS2, and CS3), and PCF8775 (CS4, CS5, and CS6). These fimbriae are associated with certain ETEC O serogroups. Serogroup O159 has had no known colonization factor. We found a distinct plasmid-encoded fimbria composed of 19 kilodalton protein subunits associated with ETEC serotype O159:H4. Rabbit antibody against this purified fimbria reacted with a single 19-kilodalton protein band as seen by Western immunoblot of sheared-cell preparations. The rabbit antibody, treated with colloidal-gold-labeled goat anti-rabbit immunoglobulin G, bound specifically to fimbriae when cells were examined with an electron microscope. Of 10 available ETEC O159:H4 strains from Europe, Bangladesh, and Kenya, 6 expressed this type of fimbria; its true prevalence among ETEC strains is unknown. This putative colonization factor of O159:H4 joins other ETEC fimbriae as potentially useful immunogens against human diarrhea. PMID- 2883124 TI - Detection of subunits of pertussis toxin in Tn5-induced Bordetella mutants deficient in toxin biological activity. AB - Monoclonal antibodies with specificity for pertussis toxin subunits S1, S2, and S4 were used in Western blots to show that the subunits were not secreted into culture medium from Tn5 insertion mutants. The mutants are deficient in toxin biological activities due to an insertion in the S3 subunit structural gene. The Western blots demonstrated that each of the respective subunits was exported in a wild-type strain. Anti-S1 and anti-S2 monoclonal antibodies were capable of detecting subunits in solubilized whole-cell material from a wild-type strain and from the Tn5 mutants lacking only in biologically active toxin (Tox-). Another Tn5 insertion mutant, lacking all known B. pertussis virulence factors (Vir-), did not produce any of the subunits either in whole cellular extracts or in culture supernatants. The data demonstrate that Tn5 Tox- insertion mutants, though defective in toxin activity, synthesize some toxin subunits. The presence of the S3 subunit is most likely a necessity for transport of the toxin from cells. Alternatively, a nonstructural gene coding for a protein involved in transport of the toxin across the membrane may be affected by the Tn5 mutation. PMID- 2883126 TI - Partition of heat-labile-enterotoxin genes between human and animal Escherichia coli isolates. AB - Heat-labile toxin (LT) genes from human and animal Escherichia coli isolates from a restricted geographical region (Thailand) exhibited a segregated pattern of dissemination that was revealed by a restriction enzyme site polymorphism. The results suggest an exclusion of LT genes from or a low transfer rate for LT genes between E. coli strains infectious for humans and those infectious for animals in natural settings. PMID- 2883125 TI - Expression of the S-1 catalytic subunit of pertussis toxin in Escherichia coli. AB - The S-1 subunit of pertussis toxin was expressed as a fusion protein in a strain of Escherichia coli deficient in protein degradation. The fusion protein reacted with anti-pertussis toxin antibody, and, like authentic pertussis toxin, it ADP ribosylated a 41,000-molecular-weight membrane protein from human erythrocytes. PMID- 2883127 TI - Epidemiological aspects of fecal colonization with P-fimbriated Escherichia coli in neonates. AB - Fecal colonization with P-fimbriated Escherichia coli has caused epidemic outbreaks of extraintestinal E. coli infections in the neonatal unit of Danderyd Hospital. The aerobic fecal flora was therefore studied in 1,955 newborn children born at Danderyd Hospital during a period of 2.5 years. E. coli was found in 58% of the maternity ward children and in 57% of the neonatal unit children. A P fimbriated strain was found in 12% and 17% of the children, respectively (p less than 0.01). There was a significant increase in the frequency of children colonized with E. coli, and especially P-fimbriated E. coli, with length of stay in the neonatal unit. There was a statistical correlation between bed occupancy and colonization with P-fimbriated E. coli (r = 0.46, p less than 0.01) during this study period. We found an incidence of P-fimbriated E. coli of 10 to 20% among the E. coli strains isolated from the fecal specimens which we regard as the baseline incidence. PMID- 2883128 TI - Time-course of IgE binding to rat peritoneal cells after sensitization with alum adsorbed ovalbumin and Bordetella pertussis. AB - High IgE responder rats were sensitized intraperitoneally with alum-adsorbed ovalbumin and Bordetella pertussis organisms. At day 0, 7, 14, 21 and 28 following sensitization the peritoneal cells were harvested and further processed for light and immunoelectron microscopical investigations using a specific anti rat IgE immunogold sandwich method. The results obtained show that the number of peritoneal mast cells increase significantly during the course of sensitization. There is a time-dependent increase in the amount of immunogold particles on mast cell surfaces together with a shift of particle distribution towards the surface folds. Sensitized mast cells exhibit altered releasability as is indicated by slightly degranulated cells at day 21 and day 28 postsensitization. Additionally, about 25% of small lymphocytes which had entered the peritoneal cavity between day 7 and day 14 are heavily stained with the immunogold complex between day 14 and day 28 postsensitization. This is not so for macrophages (less than or equal to 0.2% positive cells) nor for eosinophils which do not show any staining activity at all despite they are present in high numbers. PMID- 2883129 TI - The role of histamine in allergen and adenosine-induced bronchoconstriction. AB - We have investigated the role of histamine in allergen and adenosine-5' monophosphate (AMP)-induced bronchoconstriction in asthmatic subjects by performing inhalation challenge tests with histamine, AMP and allergen after treatment with placebo or the potent H1 histamine receptor antagonist, terfenadine. Single concentrations of each agonist which had previously been shown to produce a 30% fall in FEV1 were used. After placebo, AMP and histamine both produced rapid bronchoconstriction reaching a maximum within 5 min and returning to within 10% of baseline after 25 min. Terfenadine inhibited this reaction to histamine completely and to AMP by 86%. The response to allergen was slower in onset and was sustained over 45 min and was inhibited 50% by terfenadine. We interpret these results as reflecting the contribution of histamine to the various airway challenges, both histamine and newly generated mediators comprise the response to allergen, whereas AMP selectively enhances mast cell degranulation without affecting the production of arachidonic acid derived mediators. PMID- 2883130 TI - The role of leukotriene-inducing and -metabolizing enzymes in inflammation. AB - Leukotrienes are potent mediators of allergy and inflammation. Polymorphonuclear granulocytes which participate in acute and chronic disease processes can be activated by immunological and nonimmunological stimuli to generate leukotrienes. It appears that on activation of the cells 5-lipoxygenase is released into the supernatant and thus may exert a potent role with regard to interdependent cellular interactions. The release of leukotriene-metabolizing enzymes (e.g., gamma-glutamyl-transpeptidase, dipeptidase) is stimulus-dependent. Polymorphonuclear granulocytes alter their release profile once the cells have been prestimulated. Thus, a precise knowledge on the leukotriene-inducing and metabolizing enzymes is of utmost importance for future immunopharmacological interventions. It appears that the enzyme activity reflects the state of cellular activation. PMID- 2883131 TI - Application of histamine-induced conjunctivitis to the assessment of a topical antihistamine, levocabastine. AB - In an animal model, topical application of levocabastine to the eye inhibits the inflammatory conjunctival response to topically applied histamine. This is so even at one-fourth the concentration at which levocabastine is normally dispensed. Total blocking of histamine response continues for 24 h and is then irregularly observable for an additional 72 h. Levocabastine may be absorbed through the conjunctiva to give systemically transmitted protection to the contralateral eye. Levocabastine is a potent competitor against histamine for conjunctival H1 receptors and should prove a useful, possibly long-acting drug for the reversal of inflammatory conjunctivitis and inhibition of its recurrence. PMID- 2883132 TI - Effect of a new selective H1 receptor antagonist (levocabastine) in a nasal and conjunctival provocation test. AB - Levocabastine is a new selective H1 receptor antagonist. The effect of the drug administered locally was compared to placebo in a quantified nasal and conjunctival provocation test with allergens performed in patients allergic to grass pollen. In the nasal provocation test, levocabastine was able to increase the 'reaction threshold' (dose of allergen necessary to trigger allergic symptoms) in 9 out of 12 patients; the drug inhibited rhinorrhea and sneezing, but not nasal obstruction. In the conjunctival provocation test, the 'reaction threshold' clearly increased in 10 out of 11 patients. The local administration of levocabastine might be useful in allergic rhinitis and conjunctivitis. PMID- 2883133 TI - Ultrastructural effects of cadmium on the epididymis of the cryptorchid rat. AB - The short-term (90 min) effect of an intraperitoneal injection of cadmium chloride (3 mumol/100 g body weight) was studied with the electron microscope in the epididymis of mature rats rendered unilaterally cryptorchid 60 days before injection. It was found that the endothelium of the epididymal capillaries of the cryptorchid organ, at this low dose and short time, showed neither separation of cytoplasmic leaflets, nor platelet damage, nor extravasation, which are the lesions previously described by us and which were present in the contralateral, scrotal epididymis. The possible mechanisms for the protective action of cryptorchidism against the effects of cadmium on capillary endothelia are discussed. PMID- 2883134 TI - Acute febrile mucocutaneous lymph node (Kawasaki) syndrome. An analysis of 24 cases. AB - Twenty-five cases of Kawasaki syndrome were seen over a 6-year period at Children's Hospital in Louisville, Kentucky. The diagnosis of Kawasaki syndrome was established in all cases by use of the criteria developed at the Center for Disease Control (CDC). The medical files of these cases were systematically reviewed for epidemiologic, clinical, laboratory, and therapeutic features. The results of this study were comparable to findings from previously reported series. In contrast to previous data, we found several cases in which the febrile illness was associated with a viral infection. Two children developed coronary aneurysms, but there were no deaths, and resolution of the aneurysm occurred in one of the patients. There were no clustering of cases and no unusual epidemiologic findings; none of the patients had a recurrence. Patients with Kawasaki syndrome should be followed closely during both the acute febrile and the convalescent phases. Similar conditions in a child with a fever and a rash need to be excluded. PMID- 2883135 TI - Sterilization: the woman who changes her mind. PMID- 2883136 TI - Unexpectedly low ratio and falling incidence rate of ectopic pregnancy in Enugu, Nigeria, 1978-1981. AB - The demographic characteristics and subsequent pregnancy rate of women with tubal ectopic pregnancy have been investigated at the University of Nigeria Teaching Hospital, Enugu. The ratio of ectopic pregnancy to total births was 1:287. Ectopic pregnancy accounted for 6.2% of all gynaecological emergencies at the hospital and was the third most common of such emergencies. Nearly 69% of the women with ectopic pregnancy had delivered two or more babies previously, and the post-ectopic pregnancy conception rate was 19.54%. Surprisingly, the rate of ectopic pregnancy fell from 1:190 in 1978 to 1:480 in 1981. Ectopic pregnancy is not obviously influenced by maternal age or parity in Enugu, but is prevalent in women with previous pelvic inflammatory disease. PMID- 2883137 TI - Ureaplasma urealyticum in semen for artificial insemination: its effect on conception and semen analysis parameters. AB - Semen specimens from 24 donors in an artificial insemination program--selected for women whose infertile status was determined to be male factor-related and for whom no female factor could be determined--were cultured for the presence of Ureaplasma urealyticum. A life table statistical analysis indicated that conception did not occur sooner in the U. urealyticum-negative group (n = 14) compared with those women inseminated with the U. urealyticum-containing semen (n = 10). In addition, no significant differences were detected in semen analysis count, grade, or motility between semen with or without U. urealyticum. We found no differences in the occurrence of fetal morbidity or mortality in ten conceptions between the women impregnated with Ureaplasma-positive (n = 14) and Ureaplasma-negative (n = 6) semen. Thus, our study does not support the role of U. urealyticum as a cause of male factor-related infertility or early pregnancy loss. PMID- 2883138 TI - Results of human menopausal gonadotropin therapy at the Boston Hospital for Women (1979-1981). AB - To evaluate our results with induction of ovulation with human menopausal gonadotropins, we reviewed our experience from 1979 to 1981. Twenty-two women and 89 treatment cycles were evaluated. The patients were assigned to group 1 (amenorrhea, low FSH and LH, and no evidence of endogenous estrogens, as indicated by lack of withdrawal bleeding after medroxyprogesterone acetate) or group 2 (amenorrhea, with normal gonadotropins and evidence of endogenous estrogens by progestin withdrawal bleeding). Three patients underwent HMG therapy for inadequate luteal phase; none of them became pregnant. All patients from group 1 became pregnant (8/8), and 45% (5/11) of patients from group 2 became pregnant. The difference in pregnancy rates is significant (P less than .05). The cumulative pregnancy rate for each group was calculated by the life table method. All the cases of multiple gestation (three) came from group 1, and all the cases of ovarian hyperstimulation (five) came from group 2. In summary, in our experience patients from group 1 had a higher pregnancy rate and a greater incidence of multiple gestation than patients in group 2, who had a greater chance of developing ovarian hyperstimulation. PMID- 2883139 TI - The efficacy of progesterone in achieving successful pregnancy: I. Prophylactic use during luteal phase in anovulatory women. AB - We have previously shown that prophylactic supplementation of progesterone beginning in the luteal phase of patients treated with human menopausal gonadotropins (hMG) could reduce the risk of spontaneous abortions. The present study was initiated with 100 patients to evaluate the efficacy of a new progesterone therapeutic regime in patients requiring either hMG or clomiphene citrate. A significantly decreased risk of spontaneous abortion (6% vs. 28%) was seen in 50 patients prophylactically treated with progesterone as compared with 50 control patients. The progesterone regimen was then tried on 566 consecutive patients who were treated and conceived with hMG or clomiphene citrate, and approximately the same risk (6.2% by 20 weeks) was found. This incidence of spontaneous abortion is even less than the accepted risk for the general population. PMID- 2883140 TI - The efficacy of progesterone in achieving successful pregnancy: II. In women with pure luteal phase defects. AB - Controversy still exists as to the proper therapy of luteal phase defects. Some advocate using drugs to improve follicular dynamics, e.g., clomiphene citrate, while others treat luteal phase defects with progesterone. The possibility exists that in some cases the luteal phase defect is secondary to failure to produce a mature follicle, the better drug then being an ovulation-inducing drug, e.g., clomiphene. However, if the follicle is mature, then progesterone may be the best treatment. We defined mature follicle as one between 18 and 24 mm while the serum estradiol (E2) level is over 200 pg/mL. The efficacy of exclusive P therapy was evaluated in 50 women, all with a minimum of 1 1/2 years infertility and with no obvious fertility problems other than luteal phase defect. Seventy percent of the women conceived within 6 months. The abortion rate was 14.7%. The average period of infertility was 2.8 years in the 35 patients who conceived within 6 months. These data suggest that determining the degree of follicular maturation by serum E2 and pelvic sonography plus excluding the luteinized unruptured follicle syndrome by pelvic sonography helps determine the proper therapy for luteal phase defect. PMID- 2883141 TI - Myotonic dystrophy presenting as male infertility: a case report. AB - A 28-year-old man presented with azoospermia, low plasma testosterone levels, and an elevated follicle stimulating hormone (FSH) concentration. Bilateral testicular biopsies revealed tubular atrophy with normal-appearing Leydig cells. One year later, symptoms and signs consistent with myotonic dystrophy (MyD) were noted. The rarity of male hypogonadism preceding the neurological manifestations of MyD is stressed. PMID- 2883142 TI - Total and free testosterone and estradiol in human semen. AB - Total and free testosterone (T) and estradiol (E2) were determined by a radioimmunoassay technique in 30 normozoospermic and oligozoospermic human semen samples. The mean amounts of total T ranged from 25.1 +/- 7.4 to 32.5 +/- 12.2 ng/100 mL, and those of the free hormone from 7.0 +/- 2.8 to 7.9 +/- 2.3 ng/100 mL. The values for E2 were 10.5 +/- 4.4 to 11.2 +/- 4.5 pg/mL and 2.3 +/- 1.1 to 3.2 +/- 2.6 pg/mL, respectively. There was no correlation between sperm density of semen and the levels of T and E2. It is suggested that the nonspecific binding of T and E2 in semen provides a physiological reservoir for active, free T and E2 and that an appropriate ratio of free T to free E2 in semen may be crucial in the processes that lead to fertilization. PMID- 2883143 TI - Serum immunoreactive beta-endorphin in the human ovulatory cycle. AB - Daily serum immunoreactive beta-endorphin (IR-beta-EP) levels, in conjunction with luteinizing hormone, follicle-stimulating hormone, 17 beta-oestradiol, progesterone, and prolactin, were measured during the ovulatory cycle in five healthy Chinese women. Standardization of raw data by conversion to the statistical "Z scores" and composite plot of the five cycles showed that serum IR beta-EP levels fluctuated during the follicular, late luteal, and menstrual phases. A preovulatory rise occurred two to three days prior to the luteinizing hormone surge, followed by a postovulatory dip for two to three days. The concentrations of IR-beta-EP were (mean +/- S.E.M.): 85.5 +/- 10.5 pg/mL (n = 36) in the follicular phase; 92.4 +/- 36.5 pg/mL (n = 5) in the ovulatory phase; 72.3 +/- 16.6 pg/mL (n = 7) in the early luteal phase; 100.0 +/- 10.7 pg/mL (n = 38) in the late luteal phase. The values in the luteal phase were the highest of any in the ovulatory cycle. The findings suggest that the fluctuation of endogenous beta-EP is under the influence of, among other factors, ovarian sex steroids. The significance of beta-EP in the regulation of gonadotropin release during normal menstrual cycles is discussed. PMID- 2883144 TI - Effect on fertility in rats of epididymal administration of indomethacin. AB - Rods 2 mm in diameter and 8 mm long containing 25% or 50% indomethacin were implanted adjacent to each epididymis in rats of proven fertility. During the first 4 weeks after operation, fertility was reduced, but returned to normal at 5 to 10 weeks. The time of onset and duration of the effect were variable. Libido, ejaculation, and sperm motility were unimpaired. Drug-free Silastic rods had no effect on fertility. The results provide indirect evidence that prostaglandins have a functional role in the reproductive system of the male rat. PMID- 2883145 TI - Seminal fluid androgen levels in infertile patients. AB - Seminal fluid concentrations of testosterone (T), dihydrotestosterone (DHT), androstenedione (A), and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) were measured in 34 male patients of infertile couples. Patients were subdivided into oligospermic (less than 20 X 10(6)/mL) and asthenospermic (typical motility less than 20%; total motility less than 40%) groups. Steroids were measured by specific radioimmunoassay after ether extraction and celite column chromatography. 3 alpha-Diol was present in seminal fluid, and its concentration was significantly correlated with DHT (r = .49, P less than .05). In oligospermic patients, seminal levels of T (78 +/- 29 pg/mL, mean +/- SD) and DHT (323 +/- 132 pg/mL) were significantly reduced in comparison with normospermic men (T, 119 +/- 56, P less than .05; DHT, 557 +/- 255, P less than .01), while A and 3 alpha-diol concentrations were similar in the two groups. Seminal T and DHT levels were also reduced in asthenospermic specimens, which showed increased 3 alpha-diol concentrations (75 +/- 44 pg/mL) with respect to normokinetic samples (45 +/- 20, P less than .05). Finally, a positive linear relationship was observed between DHT and both sperm density (P less than .01) and total motility (P less than .01). These data demonstrate the existence of a significant amount of 3 alpha diol in seminal plasma and suggest DHT as the androgen most closely related to sperm quality. PMID- 2883147 TI - Biochemical characterization of a rat spermatozoal peptide antigen and the induction of a reversible immunosuppression of fertility. AB - A rat spermatozoal polypeptide with 40 amino acid residues and a N-terminal lysine was purified to homogeneity by high performance liquid chromatography. Following incorporation of the peptide into pure phosphatidylcholine liposomes and immunization of female Wistar rats, a significant reduction of fertility occurred (chi 2 = 6.4, P less than .01). Following 4 months of recovery after the immunization fertility rates returned to normal. No adverse side effects on vital organs from the immunization were detected by light microscopy. The results may be indicative of a pathway for immunologic regulation of fertility. PMID- 2883146 TI - Cytoplasmic and nuclear progesterone receptors in human fallopian tube and their relationship to plasma steroids during the menstrual cycle. AB - Progesterone (P) binding sites in the ampullary and isthmic regions of the fallopian tube and corpus myometrium were measured during the follicular, ovulatory, and luteal phases. Both cytosolic and nuclear fractions were used for P receptor determination. The concentrations of P receptors were similar in the isthmus and myometrium in all three phases. Although the absolute concentration of nuclear P receptor was always lower than that of the cytosolic receptor, the overall pattern of receptor concentration in the different regions was the same, being highest in the ampulla. Both cytosolic and nuclear receptor concentrations in all tissues were lowest in the luteal phase and highest in the ovulatory phase. In all tissues examined in the luteal phase the cytosolic P receptor but not the nuclear receptor was inversely related to plasma P concentration. The data are compatible with a dual control of P receptors by estrogen and P. PMID- 2883148 TI - Beta-endorphin. Biological activity of analogs containing dermorphin and dynorphin sequences: ileum and vas deferens assays. AB - Biological activity of synthetic beta-endorphin (beta-EP) analogs containing dermorphin or dynorphin-A-(1-13) structure has been investigated using the guinea pig ileum and the vas deferens of the mouse, rat and rabbit. Replacement of NH2 terminal 1-7 segment of camel beta-EP [beta c-EP-(1-7)] with dermorphin caused a great increase in opiate potency of the analog. [Dermorphin (1-7)]-beta c-EP was 120 times more potent than beta c-EP in the guinea pig ileum assay, 49 times more potent in the mouse vas deferens assay; and only 4 times more potent in the rat vas deferens assay. Replacement of NH2-terminal 1-13 segment of human beta-EP [beta h-EP-(1-13)] with dynorphin-A-(1-13) caused an increase in opiate potency in both the guinea pig ileum and rabbit vas deferens assays, a complete loss of potency in the rat vas deferens assay, and no change in the mouse vas deferens assay. In comparison with dynorphin-A-(1-13), the hybrid peptide was less potent in the guinea pig ileum assay as well as in mouse and rabbit vas deferens assay. It is suggested that beta c-EP-(8-31) facilitates the dermorphin moiety to act on opiate mu and delta receptors but not on the epsilon receptor, while beta h-(14 31) reduces the action of dynorphin on mu, delta and kappa receptors. PMID- 2883149 TI - Conformational analysis of two somatostatin analogues by 1H 500 MHz n.m.r. spectroscopy. AB - A series of nine closely related somatostatin analogues, containing the hexapeptide H-Cys2-Phe3-D-Trp4-Lys5-Thr6-Cys7-NH2 sequence have been synthesized by Bauer et al. The conformational properties of two of them, showing intermediate activities between those of SMS 201-995 and somatostatin, have been studied by high field n.m.r. spectroscopy in DMSO. Assignments were made using 2D n.m.r. methods, in particular NOESY experiments and detection of long-range connectivities in aromatic residues. In all the compounds of this series, the biologically active ones as well as the inactive ones, the n.m.r. parameters are in favour of a predominant conformation with a type II' beta turn involving amino acids Phe3 to Thr6. A clearcut correlation exists between the predominant conformation at the cystine bridge side and the activity. The presence of the exocyclic amino acids Phe1 and Thr8 (ol) plays a major role in stabilization of the active conformation. PMID- 2883151 TI - Glucagon releasing activity of a cyclic peptide related to somatostatin. AB - A possible benefit of creating smaller and more rigid active analogs of somatostatin is the discovery of compounds which selectively inhibit the secretion of insulin, glucagon or growth hormone. A series of cyclic tetrapeptide analogs related to somatostatin was synthesized, and one member of this series was found to cause an unexpected stimulation of glucagon secretion while having little if any effect on either insulin or growth hormone secretion. A sustained increase in plasma glucose levels was also observed. Two possible modes of action are proposed. PMID- 2883150 TI - Synthesis of two biologically active fluorescent probes of thymopentin. AB - This study reports on the synthesis of two fluorescent analogues of thymopentin (TP-5; Arg-Lys-Asp-Val-Tyr). A fluorescein isothiocyanate labeled analogue (FITC TP-5) and a stilbene isothiocyanate labeled analogue (SITS-TP-5) were extensively purified by ion-exchange and gel filtration chromatography. Characterization of the coupling site through amino acid analysis, dansylation and N-terminal cleavage of the fluorescent amino acid yielded results which indicated that both were mono-labeled analogues derivatized at the N-terminal. These analogues were shown to be TP-5-like in nature by their ability to induce the expression of the Thy 1.2 surface marker on nude mouse prothymocytes in both in vivo and in vitro assays. In addition, these analogues were able to inhibit the specific binding of radiolabeled TP-5 to human lymphocytes. Initial studies describing the interaction of FITC-TP-5 with human lymphocytes are shown. PMID- 2883152 TI - [Treatment of chronic inflammatory intestinal diseases with 5-aminosalicylic acid]. PMID- 2883153 TI - [Consequences of therapeutic long-term achlorhydria]. PMID- 2883154 TI - Clinical features, treatment and outcome of polyarteritis nodosa. PMID- 2883156 TI - Lysozyme and complement-dependent lysis of Entamoeba histolytica. Inhibition by leupeptin. PMID- 2883155 TI - Virulence of Entamoeba histolytica correlates with the capacity to develop complement resistance. PMID- 2883157 TI - Growth hormesis: a by-product of control. AB - Data from experiments, in which colonies of a hydroid, Laomedea flexuosa, were exposed to a range of Cu2+ concentrations and a marine yeast, Rhodotorula rubra, was exposed to a range of Cd2+ concentrations, not only exhibit hormesis, but also suggest how its occurrence in growth experiments might be explained. When growth data are considered as normalized specific rates against a time base, their oscillatory form indicates the output of a growth regulatory mechanism whose behaviour can be used to interpret the typical concentration-response curve exhibiting hormesis. Advantages may be conferred upon organisms whose growth control mechanisms overcorrect in response to low levels of inhibitory loading by toxic agents (stimulus), while at higher concentrations it is the overloading of such control mechanisms that results in the threshold in concentration-response curves (inhibition). It is suggested that if different examples of hormesis share a common explanation, it lies in the behaviour of homeostatic and homeorhetic feedback mechanisms, which respond to perturbation non-specifically and may overcorrect for adaptive reasons to low levels of inhibitory challenge. PMID- 2883158 TI - Presence of cell wall lytic enzyme in stable staphylococcal L-form. PMID- 2883159 TI - Antral somatostatin contents and acidity of gastric juice in normal subjects and patients with duodenal ulcer. PMID- 2883160 TI - Proteases in the human full-term placenta. AB - Aminopeptidase A, not yet defined aminopeptidases and endopeptidases, dipeptidyl peptidase I, II and IV, gamma-glutamyl transferase and oxytocinase were investigated in the normal human full-term placenta using qualitative (catalytic) cytochemistry, isoelectric focusing, immunocytochemistry and kinetic fluorometry. Aminopeptidase A could be visualized cytochemically in the smooth muscle cells of the chorionic plate, stem villi and basal plate blood vessels. Aminopeptidases were found in connective tissue fibres of the chorionic plate, villous stroma, basal plate and paraplacenta. Dipeptidyl peptidase IV was detected at the same sites as the aminopeptidases and, in addition, in amniotic epithelial cells, fibroblasts of the villous stroma, endothelium of chorionic plate and villous blood vessels as well as in the basophilic cytotrophoblast cells (x-cells) of the basal plate and paraplacenta, and it possibly also occurred in some domains of the plasma membrane of the syncytiotrophoblast and cytotrophoblast cells. The x cells surrounded the fetus in the form of a dipeptidyl peptidase IV-positive shell at the border to the mother. The enzyme represented the first specific marker for x-cells. Dipeptidyl peptidase I and II were primarily found in Hofbauer cells (macrophages) of the villous stroma, but also in the syncytiotrophoblast, other villous stromal cells and cells of the chorionic and basal plate. gamma-Glutamyl transferase was present in some connective tissue elements of the chorionic plate. Oxytocinase and endopeptidases were not detected. Isoelectric focusing of proteases revealed different molecular forms of dipeptidyl peptidase IV in the paraplacenta and villous tree, while the aminopeptidases shared the same pattern in both regions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883162 TI - Le(s)t reason prevail. PMID- 2883161 TI - HLA class II DNA analysis by RFLP reveals novel class II polymorphism. AB - Polymorphism of the HLA-D/DR region has been defined by serologic and cellular methods. Additionally, protein and DNA analyses not only confirmed and refined the definition of the established polymorphisms but also revealed further polymorphisms for which no serologic or cellular correlate are known (yet). To study these in more detail, we analyzed the banding patterns obtained from Southern blot hybridizations with DR beta and DQ alpha cDNA probes. Specific fragments reflecting already defined polymorphisms could be identified. A refined HLA-D/DR definition based upon the presence of DNA subtypes could be introduced. Fragments have also been identified that are associated with the DR/Dw specificities. Moreover, individuals with different DR types may also share fragments in hybridization assays. These shared hybridizing fragments (SHFs) are, for instance, found in individuals typed as DR4, DR5, DR7, and DRw8. In total, 20 SHFs were found using two restriction enzymes and the DR beta and DQ alpha cDNA probes. Some of these SHFs correlate with antigenic determinants defined by broad reacting alloantisera, such as DRw52, but for 14 of these SHFs, no serologic equivalent has been found so far. Thus, SHFs reflect a conservation at the DNA level of the HLA class II region, which suggests that the polymorphic class II genes may be more conserved than previously thought. The possible biologic implications of conserved sequences in the HLA class II genes will be discussed. PMID- 2883164 TI - Hypocalcemia following total thyroidectomy. PMID- 2883163 TI - The viewbox. Bezoar. PMID- 2883165 TI - The legislature examines Illinois' Medical Practice Act. PMID- 2883166 TI - Induction of gamma-glutamyltranspeptidase-positive foci in rat liver by deoxycholic acid. AB - Initiating activities of the secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA), were examined in terms of the induction of gamma glutamyltranspeptidase (GGT)-positive foci in rat liver. A rapid induction model of enzyme-altered foci was utilized. GGT-positive foci were clearly induced by DCA ranging from 0.05% to 0.5% in the diet. In contrast, the induction of GGT positive foci by LCA was less pronounced and was not dose-dependent. These results suggest that DCA possesses initiating activity. PMID- 2883167 TI - Induction of tumors in the liver, urinary bladder, esophagus and forestomach by short-term treatment with different doses of N,N'-dibutylnitrosamine in rats. AB - The multipotential carcinogen N,N'-dibutylnitrosamine (DBN) was given to F344 male rats for 2 weeks at three dose levels to study the concentration dependence of its organ specificity. Groups of 20 rats were given water containing 0.25, 0.125 or 0.063% DBN for 2 weeks and then tap water only to drink until they were killed 52 weeks after the start of the experiment. DBN induced preneoplastic lesions in the liver, esophagus, forestomach and urinary bladder. Carcinoma was found only in the liver. Induction of preneoplastic focal hepatocyte lesions positive for the P-form of glutathione S-transferase (GST-P) was quantitatively dependent on the dose of DBN. In the urinary bladder, the incidences of papillary or nodular hyperplasia (PNH) and papilloma of transitional cells tended to increase at higher doses. The incidence and number per unit length of basal cell type hyperplasias of the esophageal epithelium were significantly higher in all DBN groups than in the control group, through the increase did not show a clear dose-dependency. The incidence of epithelial basal cell hyperplasia of the forestomach was significantly increased at all doses and the increase was apparently dose-related. These results indicate that even in a short-term experiment, DBN exerted multipotential carcinogenic effects. Thus, this system could be used for assay of the modifying effects of compounds administered subsequently on carcinogenesis in different organs. PMID- 2883168 TI - Hormonal control of porcine adipose tissue fatty acid release and cyclic AMP concentration. AB - Compared with adipose tissue from other mammals, porcine adipose tissue has stringent specificity for stimulation of lipolysis by analogs of norepinephrine. This study was to ascertain whether the specificity for control was reflected in the concentration of tissue cyclic AMP (cAMP). Adipose tissue slices were incubated and concentrations of tissue cAMP and free fatty acids (FA) released to the medium were measured. It was necessary to include theophylline in the incubation medium to be able to measure changes in cAMP concentration. Fatty acid release and cAMP production were increased most effectively by the beta adrenergic agonists; isoproterenol, fenoterol, dobutamine and the mixed alpha- + beta-adrenergic agonist, epinephrine. Isoproterenol-stimulated FA and cAMP production both inhibited by the beta-adrenergic antagonist, propranolol. There was no evidence for alpha 2-adrenergic inhibition of lipolysis in porcine adipose tissue because clonidine (alpha 2-adrenergic agonist) did not lower isoproterenol induced FA or cAMP levels and phentolamine, an alpha-adrenergic antagonist, did not increase epinephrine-stimulated FA release or cAMP generation. These results imply that the stringent specificity observed for stimulation of swine adipose tissue lipolysis resides in the beta-adrenergic receptor coupled to cAMP production. PMID- 2883169 TI - Water relations of solute accumulation in Pseudomonas fluorescens. AB - When Pseudomonas fluorescens was grown in a glucose salts medium adjusted with NaCl to a water activity (aw) value of 0.980, the intracellular glutamic acid concentration increased 23-fold and comprised 90% of the total amino acid pool. This increase was not observed when the aw of the medium was reduced to 0.980 with sorbitol. Sorbitol was taken up rapidly over a 30 min period and accumulated intracellularly to a level approximately two-fold greater than the concentration in the growth medium. In continuous culture, the specific rate of glutamic acid production and glucose uptake was greater at 0.980 (NaCl) than at 0.997 aw. The maintenance coefficients for glucose uptake were similar at both aw values but were 2.4-fold greater for glutamic acid production at 0.980 (NaCl) than at 0.997 aw. PMID- 2883170 TI - Effects of extracellular matrix components on the growth and differentiation of cultured rat hepatocytes. AB - Some effects of culturing adult rat hepatocytes on each of four different substrates--laminin (LN), collagen type I (C-I), collagen type IV (C-IV), and fibronectin (FN)--have been investigated under defined conditions. No differential effect on the attachment of the cells to the various substrates was noted; however, the spreading of hepatocytes shortly after initial plating was most strikingly enhanced by FN, whereas LN exhibited little or no such enhancement. The two collagen substrates enhanced the spreading of hepatocytes more than did LN, but less than FN. The different substrates had no differential effect on the induction of tyrosine aminotransferase by dexamethasone and glucagon for at least the first 10 d in culture. The longevity of the hepatocytes was not changed significantly by any of the substrates, at least through the 14th d of culture. During the culture periods the hepatocytes at high cell density were maintained as confluent monolayers, regardless of the substrate on which they had been cultured. After 14 d of culture, gamma-glutamyltranspeptidase activity was highest in cells cultured on C-IV, and lowest in those on FN. DNA synthesis in cultured hepatocytes at a low cell density was highest in cells cultured on FN, with decreasing levels of this parameter in cells cultured on C IV, C-I, and LN, respectively. These results demonstrate that specific components of the extracellular matrix modulate both differentiated functions and the replication of hepatocytes cultured in serum-free medium. PMID- 2883171 TI - Regulation of the ato operon by the atoC gene in Escherichia coli. AB - The expression of the Ato enzymes, acetyl coenzyme A:acetoacetyl coenzyme A transferase and thiolase II, is required for growth of Escherichia coli on short chain fatty acids. The structural genes for these enzymes, atoD, atoA, and atoB, respectively, make up the ato operon. A 48-kilodalton protein encoded by atoC was required for the synthesis or activation of the Ato enzymes. The expression of Ato enzyme activities was inducible in atoC+ strains, constitutive in atoCc strains, and noninducible in atoC mutants. Merodiploid studies demonstrated that the atoCc allele is trans-dominant to the atoC+ allele. To study the action of the trans-acting atoC-encoded activator, the promoter of the ato operon was fused to the promoterless galK gene and introduced into a low-copy-number vector. The resulting low-copy-number fusion plasmid was introduced into atoC+, atoC, and atoCc hosts. The expression of the fused galK gene was inducible in the atoC+ host, noninducible in atoC host strains, and constitutive when harbored in the atoCc host. This indicated that the atoC+ and atoCc gene products act at the level of transcription, stimulating the expression of the ato operon. A working model consistent with these results is presented. PMID- 2883173 TI - Effect of buspirone on sexual dysfunction in patients with generalized anxiety disorder. AB - After 4 weeks' treatment with buspirone, sexual function was normalized in 8 of 10 patients with generalized anxiety disorder. Nine of the patients had reported decreased sexual function before treatment. Buspirone appears to offer a clinical advantage over existing anxiolytics, which are usually associated with impairment of sexual function. PMID- 2883174 TI - Very low-dose neuroleptic treatment in two patients with agitation associated with Alzheimer's disease. AB - Two agitated patients with Alzheimer's disease who either failed to respond or worsened with conventional low-dose neuroleptic and other pharmacologic treatment are described. Both patients demonstrated sustained improvement with very low dose neuroleptics, one with haloperidol 0.125 mg and the other with thioridazine 5 mg. Clinical, pharmacokinetic, and pharmacodynamic factors that may have accounted for this response are discussed. PMID- 2883172 TI - Characterization of type 1 and mannose-resistant fimbriae of Erwinia spp. AB - Type 1 fimbriae from Erwinia carotovora subsp. carotovora and mannose-resistant fimbriae from Erwinia rhapontici were purified and characterized. The type 1 fimbrillin had an apparent molecular weight of 16,500; that of the mannose resistant fimbrillin was 18,000. The amino-terminal amino acid sequences of the two fimbrillins were related, but tryptic peptide maps showed significant differences between the proteins. No serological cross-reaction was found between the two fimbrial filaments, nor did they cross-react with type 1 or type 3 fimbriae purified from other enterobacterial species. Immunofluorescent staining of bacterial populations revealed that they were heterogeneous with respect to fimbriation. PMID- 2883175 TI - Dementia and antipsychotic drugs. AB - Introduced in the 1950s, antipsychotic agents have been found to improve symptomatology and function in young and middle-aged psychotic schizophrenics. Three decades of research, however, have not made clear these agents' usefulness in demented elderly patients. A review of placebo-controlled studies suggests a definite but limited role for antipsychotic medication in behaviorally disturbed elderly dementia patients with agitated behavior. Studies also suggest that cognitive function needs careful monitoring when these drugs are prescribed to treat behavioral symptoms of dementia. PMID- 2883176 TI - Treatment of the elderly agitated patient. AB - Research studies and general literature support the careful use of neuroleptics for control of agitation-related symptoms in the elderly if the symptoms are severe enough to disrupt normal functioning. No one neuroleptic has been found to be more effective than others; medication choice should therefore be based on differential toxicity rather than differential therapeutic efficacy. The differences in frequency and intensity of neuroleptic side effects are discussed, and the use of nonneuroleptic agents, including beta blockers, in the treatment of agitation is considered. PMID- 2883177 TI - Recent advances in the neurochemistry of Alzheimer's disease. AB - This article reviews recent progress in research in the genesis of neurochemical changes in the Alzheimer brain, which has been primarily in two areas: the cellular proteins associated with the pathologic structures and the neurotransmitter changes. Research and clinical implications of recent studies and of works in progress are provided. PMID- 2883178 TI - Ontogenic changes in metabolism and transport of glutathione in the rat. AB - Changes in the level of glutathione (GSH), the turnover rate, and gamma glutamyltransferase (GGT) activity were examined in newborn, weanling, and adult male Wistar rats, the objective being to elucidate the mechanisms which control the hepatic GSH level during maturation as well as under conditions of different degrees of protein ingestion. The hepatic GGT activity in the newborn rats was high at birth, decreased within a few days to 1 to 2% of the initial level, and remained unchanged thereafter, when these rats were fed a normal diet after 3 weeks of age. In contrast, the hepatic GSH level increased 3-4-fold while total GGT activity in the kidney increased 6-8-fold. When weanling rats were fed a low protein diet (containing 10% soy protein) for 3 weeks, the hepatic GSH level decreased markedly while the GGT activity increased 5-6-fold. The turnover rate of hepatic GSH also increased, as determined by the use of buthionine sulfoximine, a specific inhibitor of GSH synthesis; a value of 2.1 h was obtained in comparison with 3.5 h for that of rats fed the normal laboratory chow (CRF-1). On the other hand, feeding adult rats on the low protein diet resulted in a marked decrease in hepatic GSH level with no effect on either hepatic or renal GGT activity. These results together with other observations may suggest that GSH translocated out of liver cells in the newborn rats is degraded mainly by these cells, while the tripeptide secreted by hepatocytes of adult rats is metabolized predominantly in extrahepatic tissues, such as the kidney.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883180 TI - Interaction of cytoplasmic tyrosine hydroxylase with chromaffin granule. In vitro studies on association of soluble enzyme with granule membranes and alteration in enzyme activity. AB - The interaction of soluble tyrosine hydroxylase with isolated chromaffin granule membranes was studied. The incubation of the granule membranes with the soluble fraction in the mixture that may approximate the intracellular environment of the resting cell resulted in a marked increase in the enzyme activity recovered in the membrane fraction, and enzyme activity precipitated with the granule membranes was increased according to incubation time and dependent on amounts of both the granule membranes and soluble fraction. The association of the soluble enzyme with the granule membranes was reversible and specific, whereas a decrease in activity of the soluble enzyme was observed when the soluble fraction was incubated with the granule membranes in the mixture in which association of the soluble enzyme with the granule membranes might occur. These results seem to indicate that activity of the soluble enzyme is presumably modulated by the granule through association of the soluble enzyme with the surface of the granule, thus suggesting that interaction between tyrosine hydroxylase and the chromaffin granule may play a possible role in regulation of catecholamine biosynthesis as a consequence of modulating activity of the rate-limiting enzyme within the cell. PMID- 2883179 TI - Measurement of proton pump activity of the thermophilic bacterium PS3 and Nitrobacter agilis at the cytochrome oxidase level using total membrane and heptyl thioglucoside. AB - It is possible to prepare liposomal vesicles by solubilization of total bacterial membranes with n-heptyl beta-D-thioglucoside followed by reconstitution into proteoliposomes by a freeze-thaw-sonication procedure with soybean phospholipids. The resulting proteoliposomes from total membrane fraction of sufficiently aerated cells of the thermophilic bacterium PS3 containing cytochrome aa3 showed a reasonable H+ pumping activity upon addition of reduced cytochrome c. On the other hand, the proteoliposomes reconstituted from air-limited PS3 cells containing cytochrome o and those from Nitrobacter agilis cells containing cytochrome aa3 did not show H+ pumping upon addition of reduced cytochrome c, although the vesicles showed "respiratory control"; 3-4-fold stimulation of oxygen consumption took place upon addition of an uncoupler. In proteoliposomes prepared from PS3 membranes by this method, H+-translocating ATPase (F0 X F1) was successfully reconstituted as well, suggesting that this method has wide applicability for investigation of enzymes catalyzing transmembrane processes. PMID- 2883181 TI - Fo portion of Escherichia coli ATP synthase. Further resolution of trypsin generated fragments from subunit b. AB - F1-stripped everted membrane vesicles of the ATP synthase-overproducing Escherichia coli strain KY 7485 were treated with trypsin for different lengths of time. Subsequently, the Fo complex was isolated and analyzed by sodium dodecyl sulfate-gel electrophoresis, as well as immunoblotting using antibodies raised against subunit b. By these techniques 3 degradation products with apparent molecular masses of about 16 kDa could be detected in accordance with previous findings (Perlin, D.S., and Senior, A.E. (1985) Arch. Biochem. Biophys. 236, 603 611). Labeling of isolated trypsin-treated Fo fractions with the thiol-specific reagent N-(7-dimethylamino-4-methylcoumarinyl)-maleimide, which has been demonstrated recently to specifically modify subunit b (Schneider, E., and Altendorf, K. (1985) Eur. J. Biochem. 153, 105-109) revealed that the 16-kDa digestion products were degraded into two stable fragments of 12 and 8.3 kDa. These polypeptides do not react with the anti-b antibodies. Treatment of purified liposome-integrated Fo with trypsin resulted in a similar cleavage pattern. In both cases protease digestion inhibited F1 binding while proton-translocating activity remained unaffected. However, liposomes reconstituted with Fo isolated from trypsin-treated membranes were impaired in both binding of F1 and proton translocation. These activities could be restored when reconstitution was carried out in the presence of native subunit b. From this we conclude that the C terminal region of subunit b is necessary for proper reconstitution of Fo into liposomes. PMID- 2883183 TI - Adenosine stimulates guanylate cyclase activity in vascular smooth muscle cells. AB - Good evidence exists to indicate that the vasodilating effect of adenosine is mediated by cell surface receptors on vascular smooth muscle cells. The mechanism of transmembrane signal transduction for adenosine, however, is not fully understood. Since cGMP is a second messenger known to mediate vasodilation, I have examined the effect of adenosine on the intracellular concentration of cGMP in vascular smooth muscle cells from rat aorta. I found that adenosine at 10(-9) to 10(-5) M led to an increase in intracellular cGMP levels in a dose-dependent fashion. The effect of adenosine on cyclic guanosine inorganic monophosphate (cGMP) could be mimicked by the A-type receptor agonists N6-cyclohexyladenosine and 5'-N-ethylcarboxamidoadenosine and was attenuated by the A-receptor antagonist theophylline. The order of potency of the adenosine analogues was N6 cyclohexyladenosine greater than 5'-N-ethylcarboxamidoadenosine greater than adenosine. These findings suggest that the effect of adenosine on cGMPi is mediated by A1-type cell surface receptors. Concerning the mechanism by which adenosine could elevate cGMPi, I found that the effect of adenosine on cGMPi was potentiated by the cGMP phosphodiesterase-specific inhibitor M & B 22948. Moreover, I found that N6-cyclohexyladenosine, 5'-N-ethylcarboxamidoadenosine, and adenosine stimulated a guanylate cyclase in homogenates of the cultured smooth muscle cells in a dose-dependent fashion with the same order of potency as their effects on cGMPi. Further evidence was obtained to indicate that adenosine and its analogues stimulated a particulate guanylate cyclase activity, whereas they did not alter soluble guanylate cyclase activity. Since cGMP is known as a second messenger mediating relaxation of vascular smooth muscle cells, the results obtained in this study could suggest that adenosine exerts its vasorelaxing effect by activating an Ai-receptor-linked guanylate cyclase. PMID- 2883182 TI - Rat pheochromocytoma tyrosine hydroxylase is phosphorylated on serine 40 by an associated protein kinase. AB - Tyrosine hydroxylase, a key enzyme in the biosynthesis of catecholamines, was previously shown to be phosphorylated on four distinct serine residues in PC12 cell cultures, each one being specific for the kinase system involved (McTigue, M., Cremins, J., and Halegoua, S. (1985) J. Biol. Chem. 260, 9047-9056). A cAMP- and Ca2+-independent protein kinase was found to be associated with tyrosine hydroxylase purified from rat pheochromocytoma tumor. The use of this activity and the availability of a large amount of purified tyrosine hydroxylase allowed identification of the site phosphorylated by this kinase activity. A peptide of 1.5 kDa (about 12 residues long), carrying the phosphorylation site, was released from 32P-labeled tyrosine hydroxylase by limited proteolysis with trypsin. This peptide was isolated from trypsinized tyrosine hydroxylase by sequential gel filtration and ion exchange chromatographies. Analysis by thin layer chromatography of an acid hydrolysate of the peptide revealed that it contained phosphoserine. The sequence determination of the peptide showed that it corresponded to the residues 38-45 in the tyrosine hydroxylase primary structure (Arg-Gln-Ser(P)-Leu-Ile-Glu-Asp-Ala). Thus, the associated kinase phosphorylated Ser-40, one of the phosphorylation sites for the cAMP-dependent protein kinase also found in rat pheochromocytoma tumors. These results are compared to those recently appearing in a report by Campbell et al. (Campbell, D. G., Hardie, D. G., and Vulliet, P. R. (1986) J. Biol. Chem. 261, 10489-10492). PMID- 2883184 TI - The defective proton-ATPase of uncD mutants of Escherichia coli. Identification by DNA sequencing of residues in the beta-subunit which are essential for catalysis or normal assembly. AB - Six mutant uncD alleles, affecting essential residues of the beta-subunit of Escherichia coli proton-ATPase, have been identified by intragenic complementation mapping, cloning, and DNA sequencing. Five of the mutations impair catalysis but do not cause structural perturbation of F1-ATPase. The amino acid substitutions found were as follows: uncD412, Gly-142----Ser; uncD430 and uncD431, both Arg-246----Cys; uncD478, Ser-174----Phe; and uncD484, Met-209--- Ile. Kinetic characteristics of each corresponding mutant F1-ATPase are described or reviewed. In each case, the major determinant of impaired catalysis appears to be an attenuation of positive catalytic site cooperativity. Additionally, each mutation affects intrinsic properties of the catalytic site, including affinity for ATP, the ratio between unisite-bound substrate and products, and the rate of release of product inorganic phosphate under unisite ATP hydrolysis conditions. These effects are discussed in terms of a structural model of the catalytic nucleotide-binding domain of beta-subunit proposed recently (Duncan, T.M., Parsonage, D., and Senior, A.E. (1986) FEBS Lett. 208, 1-6). Each of the mutations lies within that domain. The uncD409 allele abolishes normal assembly of F1-ATPase. The amino acid substitution is Gly-214----Arg, which is suggested to affect a beta-turn connecting a beta-strand and an alpha-helix in the predicted nucleotide-binding domain of the beta-subunit. PMID- 2883185 TI - Direct evidence for two distinct prosomatostatin converting enzymes. Detection using a rapid, sensitive, and specific assay for propeptide converting enzymes. AB - Many bioactive peptides are initially synthesized via larger precursors from which they are released by proteolytic cleavage at basic amino acids. Some precursors contain more than one final product peptide, multiple copies of a single peptide, or both. Different product peptides can be produced from a common precursor in different tissues. It is not currently known whether this cell-type specific production of bioactive peptides is mediated by different, specific propeptide converting enzymes (PCEs) or by a small number of similar PCEs. To resolve this issue for the conversion of prosomatostatin, the processing of prosomatostatin-I (aPSS-I) and prosomatostatin-II (aPSS-II) to either somatostatin-14 (SS-14) or somatostatin-28 (aSS-28), respectively, was examined in anglerfish islets. Two distinct forms of PSS PCE activity were detected using a rapid, sensitive, and specific assay. Examination of the specificity of these two enzyme activities showed that one proteolytic activity performs the aPSS-I to SS-14 conversion, while the other protease liberates aSS-28 from aPSS-II. The SS 14-generating PCE also cleaves aPSS-II to produce [Tyr7,Gly10]SS-14 (a tetra decapeptide analog of SS-14) and converts proinsulin to insulin. The aSS-28 generating PCE does not process proinsulin. These results provide direct evidence that different, specific PCEs are required for liberation of SS-14 and aSS-28 from their precursors. PMID- 2883186 TI - Somatostatin induces translocation of the beta-adrenergic receptor kinase and desensitizes somatostatin receptors in S49 lymphoma cells. AB - The beta-adrenergic receptor kinase is a cytosolic enzyme that specifically phosphorylates the agonist-occupied form of the beta-adrenergic receptor (beta AR). Beta AR kinase appears to be translocated from the cytosol to the plasma membrane when kin- S49 lymphoma cells are incubated with either beta-adrenergic agonists or prostaglandin E1, both of which act through receptors which stimulate adenylate cyclase. We report here that brief (approximately 20 min) exposure of wild type S49 lymphoma cells to somatostatin (which inhibits adenylate cyclase) promotes the translocation of beta AR kinase to an extent comparable to that observed in the presence of the beta agonist isoproterenol or prostaglandin E1. Beta AR kinase activity can be measured using either beta AR or rhodopsin, the retinal receptor for light, as a substrate. The translocation process triggered by somatostatin is rapid, reversible, and is associated with somatostatin receptor desensitization. The latter is apparent as an attenuation of the inhibition by somatostatin of forskolin-stimulated adenylate cyclase activity in membranes of S49 cells preincubated in the presence of the peptide. These results strongly suggest that beta AR kinase is able to phosphorylate and desensitize both stimulatory and inhibitory adenylate cyclase-coupled receptors, thus emerging as a general kinase that regulates the function of different receptors in an agonist-specific fashion. PMID- 2883187 TI - Alpha 2-adrenergic receptors accelerate Na+/H+ exchange in neuroblastoma X glioma cells. AB - The regulation of cytoplasmic pH (pHi) was examined in neuroblastoma X glioma hybrid cell-line cells (NG108-15 cells) using 2,7-biscarboxyethyl-5(6) carboxyfluorescein. The pHi of NG108-15 cells suspended in nominally HCO-3-free, Na+-containing buffer could be reduced by the external application of acetate. The recovery of pHi to its resting value was blocked by the removal of extracellular Na+, by the addition of extra-cellular H+, and by the addition of analogs of amiloride selective for inhibition of Na+/H+ exchange. The rate of recovery of pHi from acid load exhibited an ionic selectivity of Na+ greater than Li+ much greater than K+, and no recovery was observed in N-methyl-D-glucamine+. Tetrodotoxin and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid had no effect on early pHi recovery. These data suggest that Na+/H+ exchange accounts primarily for the recovery of pHi in NG108-15 cells under our experimental conditions. Na+/H+ exchange in NG108-15 cells was accelerated by alpha 2-adrenergic receptors. Thus, (-)epinephrine, but not (+)epinephrine, elicited an intracellular alkalinization which was blocked by the alpha 2-adrenergic receptor selective antagonist yohimbine but not by the alpha 1-adrenergic receptor antagonist, prazosin, nor the beta-adrenergic antagonist, propranolol. Norepinephrine, clonidine, and the clonidine analog, UK-14304, also caused alkalinization of NG108-15 cells, whereas isoproterenol, a beta-adrenergic receptor agonist, and phenylephrine, a selective alpha 1-adrenergic receptor agonist, did not. Manipulations that blocked Na+/H+ exchange blocked the ability of alpha 2-adrenergic agonists to alkalinize the interior of NG108-15 cells without blocking the ability of these agonists to attenuate cAMP accumulation. These findings provide the first direct evidence of modulation of Na+/H+ exchange activity by a receptor linked to inhibition of adenylate cyclase and offer a possible mechanism whereby alpha 2-adrenergic receptors might influence cellular activity apart from changes in cyclic nucleotide metabolism. PMID- 2883189 TI - [Effect of soldering time on the appearance of new phases. The case of Chromanit "H" with CFH soldering]. PMID- 2883188 TI - Identification of structurally distinct catalytic intermediates of the H+-ATPase from yeast plasma membranes. AB - Mild trypsin proteolysis of the H+-ATPase from yeast plasma membranes has been used to identify structurally distinct catalytic intermediates. In the absence of substrate, trypsin treatment resulted in rapid inactivation of enzyme activity. By contrast, trypsin treatment of enzyme in the presence of MgATP or MgATP plus vanadate resulted in enhanced rates of ATP hydrolysis accompanied by protection from extensive inactivation. High concentrations of Pi also induced strong protection from trypsin-induced inactivation, although enhancement of enzyme activity was not observed. Western blot analysis of peptide fragment profiles following tryptic digestion indicated that at least 15 prominent fragments of identical size, ranging from Mr = 12,800 to 48,000, were generated irrespective of digestion conditions. However, fragments from protected enzyme were resistant to further proteolysis, whereas fragments from unprotected enzyme were extensively degraded. These data have been interpreted in terms of a published catalytic reaction pathway (Amory, A., Goffeau, A., McIntosh, D.B., and Boyer, P.D. (1982) J. Biol. Chem. 257, 12509-12516) and are consistent with unprotected and protected enzyme conformations representing E1 and E2 X Pi catalytic intermediates, respectively. Trypsin proteolysis proved an effective tool for evaluating preferred enzyme conformational states and with this approach, it was found that ATPase inhibitors N-ethylmaleimide and fluorescein isothiocyanate locked the enzyme in an E1 conformation. The enhanced rate of ATP hydrolysis by trypsin-treated enzyme was fully coupled to proton transport, and all fragments generated by proteolysis were firmly bound to the membrane. These results, coupled with the fact that initial peptide fragmentation profiles were independent of enzyme conformation, suggest that the different conformational states, E1, and E2 X Pi, are not related to gross changes in overall enzyme structure but likely reflect localized changes in intramolecular bonding. PMID- 2883190 TI - Kidney proximal tubular cells isolated by collagenase perfusion grow in defined media in the absence of growth factors. AB - Cells from kidney proximal tubules have been successfully isolated, characterized, and cultured from male Fischer 344 rats between 150-400 g using a two-step collagenase perfusion. The cells undergo high levels of DNA synthesis and mitosis in both serum free media (with an without hormone supplementation) and media containing 10% fetal bovine serum. Confluent monolayers were observed between 5 to 7 days after seeding 2 X 10(5) cell/35 mm collagen-coated plate. Approximately 50% of the total kidney and 70% of the cortex was isolated using this technique. The viability of the isolated tubules was 75 +/- 8% and the estimated number of viable cells was 12 +/- 3 X 10(6) cells. At the time of isolation greater than 90% of the isolated tubules and cells were positive for gamma glutamyltransferase (GGT), periodic acid-schiff (PAS), and glucose-6 phosphatase (G-6-Pase). Both GGT and G-6-Pase decreased rapidly during the first 3 days in primary culture as assessed by histochemistry. Ultrastructurally the isolates consisted of cells with numerous microvilli and mitochondria. The size and number of microvilli decrease rapidly in primary culture. The morphologic and biochemical evidence suggests that the primary isolates and cultures are proximal tubular in origin. PMID- 2883191 TI - Specific gene expression during compensatory renal hypertrophy in the rat. AB - The compensatory growth of the kidney which is induced by unilateral nephrectomy is a highly regulated process resulting principally in hypertrophy of the remaining kidney. The events which regulate this process are unknown. We have examined the levels of transcripts for the proto-oncogenes, myc, H-ras, K-ras, and fos, and the cellular genes, H4 histone, ornithine aminotransferase, and gamma-glutamyl transpeptidase, following unilateral nephrectomy in the rat. The pattern of expression of c-myc, c-H-ras, and c-K-ras during compensatory growth of the kidney differs from the pattern of expression of these proto-oncogenes during liver regeneration, in which, unlike the kidney, hyperplasia rather than hypertrophy predominates. The lack of change in the abundance of these proto oncogene transcripts following unilateral nephrectomy suggests a primary relationship between the expression of these proto-oncogenes and DNA synthesis and indicates there may be separate signals for cell growth, one to double cell size and one to replicate DNA. Increased mRNA transcripts for the enzymes ornithine aminotransferase and gamma-glutamyl transpeptidase were induced in the contralateral kidney after nephrectomy. The time course of expression for these two enzymes differs. The early expression of the gamma-glutamyl transpeptidase gene may indicate an involvement of this glutathione-metabolizing enzyme during renal compensatory growth, while the function of the delayed increase in ornithine aminotransferase transcripts in the remaining kidney is not apparent. PMID- 2883192 TI - Initial therapy for hypertension. PMID- 2883193 TI - 125I-somatostatin analogues: high-performance liquid chromatography profiles and antibody binding properties following three methods of radioiodination. PMID- 2883194 TI - Determination of alpidem and its metabolites in human plasma by high-performance liquid chromatography and fluorimetric detection. AB - A high-performance liquid chromatographic method has been developed for the simultaneous determination of alpidem and its metabolites in human plasma. The method involved a single extraction of the parent drug and metabolites into diethyl ether from alkalinized plasma, evaporation of the organic solution and chromatography of the extracts on a C18 column coupled to a fluorimetric detector. An internal standard was used for the quantitative determination of the compounds. The method was selective for alpidem and three of its metabolites and has a limit of detection of less than 1 ng ml-1 for all the compounds. Since the chromatographic run took more than 20 min, the chromatographic process was fully automated and performed overnight. PMID- 2883195 TI - A standardized meal stimulation test of the endocrine pancreas for early detection of pancreatic endocrine tumors in multiple endocrine neoplasia type 1 syndrome: five years experience. AB - Forty-nine members of 6 families with multiple endocrine neoplasia type 1 (MEN 1) were investigated with a standardized meal stimulation test to detect the presence of pancreatic endocrine tumors. Fifteen age-matched subjects and 4 patients with primary hyperparathyroidism also were studied. Serum pancreatic polypeptide (PP), gastrin, and insulin as well as plasma glucagon and somatostatin concentrations were determined before and during the test meal. Patients with demonstrable pancreatic endocrine tumors had significantly increased mean basal and peak serum PP (P less than 0.001) and gastrin (P less than 0.001) responses to the meal compared with healthy family members and normal subjects. Seven of 12 MEN 1 patients with parathyroid and pituitary disease but no demonstrable pancreatic endocrine tumors had exaggerated PP and/or gastrin responses to the meal; 4 of them developed pancreatic endocrine tumors, detected by abdominal computerized tomography, 0.5-4 yr later. None of the healthy members of the MEN 1 families or the patients with primary hyperparathyroidism had responses different from those of the normal subjects. Our experience with the meal stimulation test indicates that an elevated basal or exaggerated serum PP and/or gastrin response is an earlier sign of pancreatic involvement in the MEN 1 trait than is abdominal computerized tomography. PMID- 2883196 TI - Medullary carcinoma of the thyroid, pancreatic nesidioblastosis and microadenosis, and pancreatic polypeptide hypersecretion: a new association and clinical and hormonal responses to long-acting somatostatin analog SMS 201-995. AB - We describe a 63-yr-old man with disseminated medullary carcinoma of the thyroid and pancreatic nesidioblastosis and microadenosis with pancreatic polypeptide (PP) hypersecretion. His major symptoms were watery diarrhea, flushing, and abdominal bloating; these and the elevated plasma PP levels did not change after resection of the distal two thirds of the pancreas, which contained a 2-cm mass of nesidioblastotic tissue. Postoperatively, a long-acting somatostatin analog, SMS 201-995 (100 micrograms/day), normalized PP secretion acutely and chronically (7 months) and ameliorated his symptoms. The analog had no side-effects and did not alter glucose tolerance, calcitonin hypersecretion, or growth of the medullary carcinoma, but it did inhibit GH secretion. After withdrawal from therapy for 1 month, PP hypersecretion and all symptoms except diarrhea recurred. The coexistence of medullary carcinoma of the thyroid and PP cell nesidioblastosis represents a new variant of the overlap syndromes between multiple endocrine neoplasia types I and II. Patients with medullary carcinoma and unexplained watery diarrhea should have fasting gastroenteropancreatic hormone assays done to screen for a potential gastrointestinal or pancreatic origin for the diarrhea. PMID- 2883197 TI - Selective alterations in immunoregulatory lymphocyte subsets in early HIV (human T-lymphotropic virus type III/lymphadenopathy-associated virus) infection. AB - In order to characterize the effects of HIV (human T-lymphotropic virus type III/lymphadenopathy-associated virus) on the immune system, Leu8- and Leu8+ subsets of CD4 and CD8 cells were studied in seropositive homosexually active men without acquired immune deficiency syndrome (AIDS). Controls included both heterosexual men and HIV-seronegative homosexually active men. The decrease in CD4 levels, observed in HIV-seropositive men who were asymptomatic, as well as in those who had persistent generalized lymphadenopathy or constitutional symptoms of HIV infection, occurred proportionally in both the Leu8- and the Leu8+ CD4 subsets. This observation, that HIV infection does not selectively diminish either subset of CD4 cells, indicates that the selective loss of T cell-mediated functions which accompanies the development of AIDS is not related to preferential loss of the Leu8+ CD4 subset. Among CD8 cells, however, HIV infection resulted in a threefold elevation in the number of Leu8- CD8 cells, while the number of Leu8+ CD8 cells remained constant. The increase in Leu8- CD8 cells was present in recent seroconverters, persistently seropositive men, and patients with AIDS. We propose that the increase in Leu8- CD8 cells represents an HIV-specific cytotoxic T-cell response. These cells may operate by killing infected CD4 cells, thereby partially controlling viral infection while simultaneously contributing to the destruction of the immune system. PMID- 2883198 TI - Cross-reactions in Legionella antisera with Bordetella pertussis strains. AB - While preparing slide agglutination test antisera and immunofluorescence conjugates for the identification of Legionella species and serogroups, we found that several of the reagents cross-reacted with Bordetella pertussis strains. To determine the extent of this problem and to estimate the specificity of Legionella reagents, we tested slide agglutination test antisera against 22 species and 35 serogroups with 92 bacterial strains representing 19 genera. The only cross-reactions observed were with Legionella pneumophila serogroup 10, L. maceachernii, L. gormanii, and L. feeleii serogroup 1 antisera and 4 of 10 B. pertussis strains. Nineteen conjugates, previously available from the Centers for Disease Control but no longer distributed as reference reagents, were tested with the four cross-reactive B. pertussis strains. Two conjugates, L. micdadei and L. wadsworthii, stained three of the B. pertussis strains at a fluorescence intensity of greater than or equal to 3+. All cross-reactions were removed from the antisera and conjugates by absorption with the cross-reacting strain without diminishing the homologous reaction. Special emphasis should be placed on the identification and removal of cross-reactions in Legionella reagents with strains that have similar morphologic and growth characteristics. PMID- 2883199 TI - Carrier detection in X-linked severe combined immunodeficiency based on patterns of X chromosome inactivation. AB - The X-linked form of severe combined immunodeficiency (XSCID) is underdiagnosed because no methods have been available for detecting carriers. Although boys with XSCID are deficient in T cells, female carriers are immunologically normal. Carriers' normal immune function would be expected if all their T cells were derived from precursors whose X chromosome bearing the XSCID mutation was inactivated early in embryogenesis. Using somatic cell hybridization to separate the active and inactive X chromosomes and restriction fragment length polymorphisms to distinguish them, we have determined the lymphocyte X inactivation pattern in XSCID carriers and their female relatives. In the T cells of three carriers, the X chromosome bearing the XSCID mutation was consistently inactive. Nonrandom X inactivation was also found in the T cells of one at-risk female, while two others had normal, random X inactivation. This method constitutes a generally applicable carrier test for XSCID. PMID- 2883201 TI - Schizophrenic thinking and neuroleptic dosage. AB - Three groups (N = 60) of schizophrenics (with varying levels of chronicity and drug dosages) were administered the Whitaker Index of Schizophrenic Thinking, the Mini-Mental State, and the Self-Conscious Scale. The results indicated that no differences existed between the chronic and acute groups on the dependent measures. Furthermore, no significant differences emerged between 21 of the acute patients who were discharged and 9 patients of the acute group who were not discharged (follow-up). No significant differences on any of the dependent measures were observed when subjects were grouped according to level of schizophrenic thinking and of neuroleptic dose. Also, no relationship between neuroleptic drug dosage and thinking for any of the three groups was observed. PMID- 2883202 TI - Controlled clinical assessment of astemizole in the treatment of chronic idiopathic urticaria and angioedema. AB - Astemizole, one of the newer generation of nonsedating antihistamines, was evaluated in a double-blind study of forty-six patients who had chronic idiopathic urticaria with or without angioedema; most had severe disease. Nineteen of twenty-three patients who were on placebo discontinued treatment because of lack of response compared to only five of twenty-three astemizole treated patients (p less than 0.0001). Fourteen of twenty-two astemizole-treated patients and two of twenty-two placebo-treated patients considered the results to be good or excellent (p less than 0.0001). Blinded assessment by the investigators yielded similar results (p less than 0.0001). Therapeutic response was the same in patients with and without angioedema in addition to urticaria and in those requiring corticosteroids. Duration of urticaria also did not influence the results. Increased appetite and weight gain were the main side effects reported more frequently in the astemizole-treated than in the placebo-treated group, and no significant toxicity was noted. Follow-up after terminating the drug study indicated a high frequency of remissions during the subsequent year. PMID- 2883200 TI - Human creatine kinase-B complementary DNA. Nucleotide sequence, gene expression in lung cancer, and chromosomal assignment to two distinct loci. AB - Using a small cell lung cancer (SCLC) cDNA library, we obtained clones for the creatine kinase-B (CK-B) gene and determined the nucleotide sequence for the protein coding and 3' untranslated region (3' UT). The human translated protein spans 381 residues and the amino acid homology with rabbit CK-B is greater than 98%. We have demonstrated that a nucleic acid probe encompassing the protein coding region will also hybridize to CK-M sequences while a probe derived from the 3' UT region is CK-B specific. When a B-isoenzyme specific sequence is hybridized to Eco RI cut genomic DNA, two independent restriction fragment polymorphisms are detected. We have subsequently localized these two CK-B homologous sequences to chromosomes 14q32 and 16. Finally, we show that increased levels of CK-B seen in SCLC are not accompanied by gene amplification or rearrangement, but reflect a greatly enhanced level of CK-B specific mRNA that is not seen in non-SCLC lines thus far examined. PMID- 2883203 TI - Studies on the putative role of gamma-glutamyl transpeptidase in intestinal transport of amino acids in Atlantic salmon. AB - The gamma-glutamyl cycle is considered to function in the membrane transport of amino acids, particularly glutamine and cysteine. When groups of Atlantic salmon were fed either a control diet containing 45% crude protein or an amino acid diet (of similar overall amino acid composition but containing elevated levels of glutamine and cysteine) for 16 weeks, weight gains were significantly greater in the former group than in those given the amino acid diet. There were no significant differences between treatments in gamma-glutamyl transpeptidase (GT) activity in the proximal intestine; in distal intestine there was significantly more activity in control fish. Mean levels of GSH were higher in tissues (pyloric caeca, distal intestine and kidney) of amino acid diet fish than in those of control fish. Glutamine was less effective as a gamma-glutamyl acceptor than several other amino acids when tested with salmon caecal GT. There were no morphological adaptations to the two feeds. Nutrient uptake studies showed an increased uptake of glutamine, but decreased uptakes of proline and methionine in proximal intestine of salmon fed amino acid diet. Much the greater part of the glutamine uptake, even at high concentrations was shown to be by Na+ dependent processes. There is no evidence that GT itself is Na+ dependent. The results do not support the view that the gamma-glutamyl cycle and GT in particular are involved in the transport of amino acids in the intestine and are discussed in this context. PMID- 2883204 TI - An explanation of renal hemodynamics in acute renal failure based on sequential CT in patients with Korean hemorrhagic fever. AB - The pattern of renal enhancement and washout of contrast medium was observed on sequential follow-up CT in 12 patients with Korean hemorrhagic fever, in which acute renal failure is one of the most important clinical features. Renal contrast enhancement and contrast medium washout were delayed longer in patients with severe oliguric renal failure. The delayed washout peaked at 4-5 days and did not return to normal until 8-9 days in the patients with severe oliguria; in the patients without severe oliguria the times were 1-2 days and 3-4 days, respectively. A characteristic "cart-wheel" pattern was observed during the washout stage in patients without severe oliguria. This "cart-wheel" pattern of washout is thought to result from relief of vasoconstriction and repair of tubular function. Multifocal "wedge-shaped" nonenhanced areas of the kidney, seen on the 2 week follow-up postcontrast CT, are thought to be ischemic zones due to persistent vasoconstriction. On the 6 week follow-up postcontrast CT in one patient, scarring of the kidney was detected in the same area that did not enhance on the 2 week CT. This scarring is thought to be a result of permanent vasoconstriction. PMID- 2883205 TI - Beliefs, feelings and insight of patients with schizophrenia about taking medication. AB - There has been little systematic study of the attitude of clients with schizophrenia toward treatment, specifically about taking medication. This study measured the attitude of 100 clients with schizophrenia toward taking their medication in the hospital. They include 47 males and 53 females ranging in age from 18 to 75 years (mean = 33). Interviews occurred on the 1st to 32nd hospital day (mean = 4). Fishbein's expectancy-value model provided the theoretical base for this study. Both open-ended and fixed-response estimates of attitude were made. Insight was measured, and the relationship between insight and attitude and between hallucinations and insight were analysed. Age and sex were evaluated in order to determine their effects, if any, on attitude. Internal consistency of both the fixed-response instruments and the insight instrument was evaluated. Clients were able to provide information about beliefs and feelings about taking medication and about insight into illness and treatment. Attitudes varied tremendously; clients frequently held both strongly positive and strongly negative beliefs at the same time. The range for the fixed-response estimate of attitude was -52 to +76; the range for the open-ended estimate was -84 to +24. However, the instruments were significantly correlated (r = 0.5640, P = less than 0.000). Clients also varied widely in their insights with some having good insight and some having poor insight. The insight instrument correlated with the fixed response instrument (r = 0.2585; P = 0.005) suggesting that insight may be related to positive attitude. Attitudes were not affected either by age or sex. Insight was negatively affected by hallucinations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883206 TI - Postnatal atresia of extraparenchymal pulmonary veins, fulminant necrotizing pulmonary arteritis and elevated circulating immune complexes. AB - An infant with operatively corrected total anomalous pulmonary venous connection developed postnatal atresia of the extraparenchymal left pulmonary veins with secondary arteritis of the ipsilateral intraparenchymal pulmonary arteries. Atresia of the right or left main pulmonary veins or of the common pulmonary vein is a rare occurrence and it is believed that association of such with necrotizing pulmonary arteritis has never been reported. This case illustrates the potential consequences of severe pulmonary venous obstruction in the absence of a left to right shunt. PMID- 2883207 TI - Pre- and postnatal development of rat retroperitoneal paraganglia. AB - The prenatal and postnatal development of the rat retroperitoneal paraganglia were studied using the formaldehyde-induced catecholamine fluorescence (FIF) method. In addition, the transmitter composition of the paraganglionic cells of the newborn rat was analyzed by immunohistochemical demonstration of the catecholamine-synthesizing enzymes. The first fluorescent preaortic cells were detected in the 13.5-day-old embryos. One day later these cells constituted a distinct organ with moderately fluorescent cells, and in 15.5-day-old embryos this organ consisted cranially of moderately fluorescent and caudally of brightly fluorescent cells. The organ reached its largest size at birth and afterwards fibrous material increased between the fluorescent cells. In 4-week-old animals, only small clusters of fluorescent cells were observed in the preaortic area although many small paraganglia were situated cranially near the coeliac ganglion. In the organ of the newborn rat, many cells showed bright FIF. In addition, some cells with only slight or moderate fluorescence as well as non fluorescent cells were detected. The analysis of immunoreactivity to the catecholamine-synthesizing enzymes showed that there was a cell population with intense reactivity to both tyrosine hydroxylase (TH) and dopamine beta hydroxylase (DBH). These cells were considered as paraganglion-type cells. Some of them were also immunoreactive to phenylethanolamine N-methyltransferase (PNMT). In addition, there were cells with weak to moderate reactivity to TH and DBH but not to PNMT. Also totally negative cells were constantly seen. These findings were confirmed by using consecutive sections for the localization of different enzymes and by using the Tramu method to elute previous staining and by restaining the same sections with the other antibodies. It is concluded that the retroperitoneal paraganglia of newborn rat consist of many paraganglion-type cells containing noradrenaline, some of them containing also adrenaline, a few neuron-like cells with TH and DBH immunoreactivity, and cells containing no catecholamines. PMID- 2883208 TI - Neuropeptide Y-like immunoreactive C1 neurons in the rostral ventrolateral medulla of the rabbit project to sympathetic preganglionic neurons in the spinal cord. AB - After injection into the thoracic spinal cord of the rabbit, gold particles coupled to concanavalin A were found in the rostral ventrolateral medulla in neurons which contained neuropeptide Y-like immunoreactivity. These cells have previously been shown to belong to the C1 catecholamine (presumably adrenaline)- synthesizing group. Nerve terminals in the intermediolateral column contained both tyrosine hydroxylase and neuropeptide Y-like immunoreactivity. When fast blue was injected into the adrenal gland the retrogradely labeled preganglionic neurons were shown to be surrounded by nerve terminals containing neuropeptide Y like immunoreactivity. Our results indicate that at least some of these terminals derive from C1 neurons which also synthesize neuropeptide Y. PMID- 2883209 TI - Analysis of mechanisms responsible for the bradycardic action of naloxone after haemorrhage in the conscious rabbit. AB - We have analyzed the efferent mechanisms responsible for the bradycardia that occurs when naloxone (6 mg/kg) is given i.v. to conscious rabbits after acute blood loss of 17-20 ml/kg. Atenolol and hyoscine methyl bromide were given intrapericardially (i.p.c.), singly and in combination, to allow factorial analysis of the contributions of sympathoadrenal beta-adrenergic and vagal cholinergic mechanisms. In addition, the effects of ganglion blockade with mecamylamine on the heart rate response to naloxone, and of i.p.c. naloxone on the cardiac pacemaker, were tested. The treatments had little effect on the pressor response to naloxone. Central nervous mechanisms were responsible for most of the bradycardia of approximately 160 beats/min evoked by naloxone in sham treated, bled, rabbits. Increased vagal drive accounted for one-half the response, withdrawal of sympathoadrenal drive for 20%, and there was no significant interaction. These effects appeared to be due to evocation of a baroreceptor-heart rate reflex by the concomitant rise in blood pressure. Non cholinergic, non-adrenergic mechanisms were responsible for a fall in heart rate of approximately 35 beats/min, part of which was due to a direct action of naloxone on the cardiac pacemaker. PMID- 2883210 TI - Differential regulation of regional vascular resistance by the rostral and caudal ventrolateral medulla in the rat. AB - Regional vascular resistance changes were determined following chemical excitation and inhibition of the rostral vasopressor (RVLM) and caudal vasodepressor (CVLM) areas in the ventrolateral medulla. Mesenteric, renal and hindquarter vascular resistances were assessed in paralyzed and artificially ventilated urethane-anesthetized rats instrumented with pulsed-Doppler flow probes. Microinjection of the excitatory amino acid L-glutamate in the RVLM elicited a significant dose-related transient increase in blood pressure, heart rate and resistance of mesenteric, renal and hindquarter vascular beds. A similar dose-related hemodynamic profile was obtained following microinjection of muscimol, a GABAmimetic, in the CVLM. In contrast, significant dose-related decrease in blood pressure, heart rate and resistance in mesenteric and hindquarter vascular beds was observed following glutamate-induced excitation of the CVLM and muscimol-induced inhibition of the RVLM. Changes in renal vascular resistance were inconsistent in this second hemodynamic profile. Intravenous administration of the alpha 1 adrenergic antagonist, prazosin, abolished all of the hemodynamic effects elicited by excitation of the RVLM except the tachycardia. Intravenous atropine methylnitrate blocked the bradycardia associated with excitation of the CVLM but did not alter the vascular resistance changes. These results indicate that the changes in heart rate did not contribute significantly to the resistance profiles described. The changes in vascular resistance elicited by excitation and inhibition of the RVLM were correlated with increase and decrease in the greater splanchnic nerve activity, respectively. In conclusion, neuron pools in the RVLM and CVLM exert differential effects upon resistance in different vascular beds via changes in sympathetic outflow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883211 TI - Early increase in adrenomedullary catecholamine synthesis in sinoaortic denervated rats. AB - Adrenomedullary catecholamines (dopamine, noradrenaline and adrenaline) and catecholamine synthesizing enzymes (tyrosine hydroxylase and dopamine beta hydroxylase) were elevated within 3 days of sinoaortic denervation in rats with neurogenic hypertension. Conversely, there were no differences in adrenomedullary catecholamines and their related enzymes 21 days after sinoaortic denervation. These results suggest an activation of adrenomedullary catecholamine synthesis at the onset of neurogenic hypertension. PMID- 2883212 TI - Evidence that dopamine regulates norepinephrine synthesis in the rat superior cervical ganglion during hypoxic stress. AB - Electrical stimulation of preganglionic nerves is known to increase norepinephrine synthesis in the rat superior cervical ganglion in vitro, an effect which appears to be partially regulated by a non-cholinergic transmitter. In the present study, we sought to determine whether sympathetic stimulation also increases norepinephrine synthesis in the rat ganglion in vivo, and whether dopamine released from ganglionic interneurons might regulate this response. To tackle these questions, rats were pretreated with spiroperidol, a selective dopamine-receptor blocker, and then were sympathetically stimulated by exposure to severe hypoxic stress. Other rats were pretreated with vehicle alone before the hypoxic exposure. Norepinephrine synthesis in ganglia was assessed by measuring endogenous tyrosine hydroxylase activity and norepinephrine turnover. We found that hypoxic stress increased both of these indices of norepinephrine synthesis, but only in rats pretreated with spiroperidol. No such response was detected in rats pretreated with vehicle. These results indicate that sympathetic stimulation increases norepinephrine synthesis in the rat superior cervical ganglion in vivo, and that dopamine released from interneurons might regulate this response. PMID- 2883213 TI - Treatment of Barrett's esophagus with H2 blockers. AB - The effect of the H2 receptor antagonists, cimetidine and ranitidine, on Barrett's esophagus was assessed in a retrospective study. There was no evidence of regression of Barrett's epithelium in the 22 patients treated for a mean of 13 months with 800-1,600 mg/day cimetidine, or in the 13 patients treated for a mean of 5.7 months with 300 mg/day ranitidine. Eight of 12 esophageal (Barrett's) ulcers healed on cimetidine therapy over a mean period of 8.7 months, and eight of nine esophageal ulcers healed on ranitidine therapy over a mean period of 3.5 months. We conclude that short-term treatment with H2 blockade does not cause regression of Barrett's esophagus, although such treatment can heal esophageal ulcers. PMID- 2883214 TI - Pharmacokinetic and dynamic studies with a new anxiolytic imidazo-pyridine alpidem utilizing pharmaco-EEG and psychometry. AB - In a double-blind, placebo-controlled study the pharmacokinetic and pharmacodynamic effects of a new imidazo-pyridine derivative, alpidem (SL80.0342) and the 1,4 benzodiazepine lorazepam were investigated utilizing quantitative EEG and psychometric testing. Ten normal volunteers received randomized (latin square) single oral doses of placebo, 25 mg, 50 mg and 100 mg alpidem and 2.5 mg lorazepam at weekly intervals. Blood level sampling, EEG recordings, evaluation of pulse, blood pressure and side-effects were carried out at 0, 1, 2, 4, 6 and 8 hours post drug; psychometric and psychophysiological investigations at the same time periods except for the first hour. Computer-assisted spectral-analysis of the EEG demonstrated an anxiolytic profile after both compounds, characterized by an increase of beta activity, decrease of alpha activity and acceleration of the centroid of the total activity and total beta activity. Total power was attenuated, delta activity augmented and the centroid of the combined delta and theta activities decreased. The latter changes were most pronounced after 2.5 mg lorazepam suggesting it is more sedative than alpidem. Dose/treatment efficacy calculations revealed 2.5 mg lorazepam as the most CNS-active compound, followed by 100 mg, 50 mg and 25 mg alpidem. Based on a multivariate analysis 2.5 mg lorazepam could be differentiated from placebo at all times, 100 mg alpidem in the first, second and fourth hours, 50 mg only in the second hour. Time-efficacy calculations showed a marked CNS effect after alpidem in the first hour with a peak in the second hour, a gentle decline to the fourth hour and thereafter a rapid decline up to the eighth hour. In contrast, 2.5 mg lorazepam showed a slower rise in CNS activity which peaked in the fourth hour and declined slowly thereafter. These pharmacodynamic effects paralleled the blood level course of both compounds, as well as the time-course of psychometric changes. The latter were characterized by a deterioration in psychometer function after 2.5 mg lorazepam, which was less pronounced after 100 mg alpidem, while 50 mg and 25 mg showed no significant difference from placebo. Subjective ratings of mood showed a decrement which was most pronounced after 100 mg alpidem, less so after 50 mg, with no difference from placebo after 25 mg or lorazepam. Finally, there were no significant inter-drug differences with regard to psychophysiological variables. PMID- 2883215 TI - Multi-resistant Staphylococcus aureus--a suitable case for inactivity? PMID- 2883216 TI - Computers and hospital infection. PMID- 2883217 TI - Hospital outbreak of multi-resistant Acinetobacter anitratus: an airborne mode of spread? AB - During a 10-month period, from October 1984 to July 1985, a multi-resistant strain of Acinetobacter anitratus was isolated from 36 patients in three neurosurgical wards, one medical ward and the intensive care unit of a district general hospital, and from two patients in the intensive care unit of a hospital in another district. Fourteen patients developed significant infection including pneumonia (10), meningitis (2), septicaemia (2) and wound infection (4). The majority of cases (28) involved the respiratory tract of ventilated patients, although respiratory equipment was not implicated as a source of the infection. The epidemic strain was recovered from the skin, nose, mouth and rectum of colonized patients and from the hands of personnel. However, extensive air and environmental contamination in the vicinity of colonized patients was also demonstrated. This is the first outbreak of infection with Acinetobacter, of which we are aware, where airborne spread has been observed. PMID- 2883218 TI - An outbreak of puerperal fever caused by group G streptococci. AB - An outbreak of puerperal fever caused by group G streptococci is described. Transmission of the organism may have occurred via contamination of automated douches. When these were disinfected and kept free of the organism the outbreak ended abruptly. PMID- 2883219 TI - Management of patients with epidemic methicillin-resistant Staphylococcus aureus: experience at an infectious diseases unit. AB - Between January 1983 and April 1984 60 patients completed their admission to an infectious diseases unit for management of methicillin-resistant Staphylococcus aureus. All had been shown to be colonized with a particular epidemic strain (EMRSA), and most isolates were from the nose or from broken skin sites. Eight patients were thought to have systemic EMRSA infection, of whom three had bacteraemia. Ten of the 60 patients died of severe underlying disease, eight were discharged home well but still colonized with EMRSA, four never had positive isolates after admission, and the remaining 38 cleared their EMRSA colonization in an average of 2 months. Five patients had further isolates of EMRSA after three negative, weekly screening tests and one after four negative screenings. No patients had further isolates after five or more negative screening tests. PMID- 2883220 TI - Prevalence survey of infection in a Hong Kong hospital using a standard protocol and microcomputer data analysis. AB - A 1-day prevalence survey of hospital infection was performed in June 1985 at a new general teaching hospital in Hong Kong. The 1980 British national survey protocol was used, and the results were analysed by microcomputer. The major part of the survey was carried out by nine people over a period of 3 days and was completed within 6 weeks. The rate of hospital-acquired infection was 8.9% and of community-acquired infection was 16.5%. Antibiotics were mainly used in infected patients. The British protocol is suitable for Hong Kong hospitals, and with microcomputer data analysis such surveys can be completed quickly and accurately even with limited resources. PMID- 2883221 TI - Outbreak of colonization of neonates with Enterobacter sakazakii. AB - An outbreak of colonization of 11 neonates with Enterobacter sakazakii occurred in a neonatal intensive care unit from the 10 September to 17 October 1984. During this period Ent. sakazakii was isolated from throat and rectal swabs and tracheal aspirates, but not from blood, of the neonates. The duration of colonization ranged from 2 to 8 weeks. The isolates were resistant to amikacin and to tobramycin, but sensitive to gentamicin. Four of the 11 colonized neonates had clinical signs of severe sepsis and one of meningitis and four died in spite of intensive chemotherapy. The source and the mode of spread of Ent. sakazakii remained unknown as it was not found on the hands of staff or in the inanimate environment of the unit. Ent. sakazakii may be implicated in severe infections in neonates and should be included when screening clinical specimens. PMID- 2883222 TI - Potential hazard from spray cleaning of floors in hospital wards. AB - The potential hazard from using contaminated spray cleaning fluid to clean hospital floors was investigated. Eight of 10 sprays in daily hospital use failed the 'in-use' test of Kelsey & Maures. Contamination was due to Gram-negative bacilli, mainly Pseudomonas spp. An experiment showed that freshly diluted cleaning fluid in a new spray container became contaminated in 6 days, although the route of contamination of the fluid is not clear. Air samples and samples from bedding collected during spray cleaning with contaminated fluid showed the presence of Pseudomonas spp. Use of freshly diluted cleaning fluid and daily cleaning of spray containers is recommended. PMID- 2883223 TI - Antibiotic prophylaxis in non-perforated appendicitis of childhood: tetracycline lavage compared with peroperative intravenous cefuroxime and metronidazole. AB - Eighty-four cases of non-perforated appendicitis in children were randomly allocated to receive either oxytetracycline lavage alone or oxytetracycline lavage plus peroperative intravenous metronidazole and cefuroxime. The wound infection rate with the oxytetracycline lavage alone was 4.4% compared with 7.7% when metronidazole and cefuroxime were added. These rates were not significantly different. This study supports the use of oxytetracycline lavage alone as effective prophylaxis against wound infection in non-perforated appendicitis of childhood. PMID- 2883224 TI - A prospective survey of hospital cross-infection with Streptococcus pneumoniae. AB - A prospective survey of pneumococcal carriage and infection between October 1984 and April 1985 in a male medical ward of a district general hospital is reported. In the hospital as a whole, pneumococcal infection, acquired more than 5 days after admission, accounted for some 20% of all pneumococcal infection. PMID- 2883225 TI - A bacteriological examination of breast pumps. AB - In an investigation of the source of an outbreak of Serratia marcescens infection in a special care baby unit, several breast pumps used in the hospital and community were examined. The epidemic strain was isolated from two pumps and other Gram-negative organisms, Staphylococcus aureus and Streptococcus faecalis were isolated from seven. The findings indicate that breast pumps may be a potential source of contamination of the user, her breast milk, infant and environment. Our recommendations regarding the use of breast pumps are presented. PMID- 2883226 TI - Role of R-plasmids in adherence and hydrophobicity in Escherichia coli. AB - Twenty-five R-plasmids from different incompatibility groups were conjugatively transferred to the laboratory strain Escherichia coli JE2571 and the variations in surface hydrophobicity and adherence to human buccal epithelial cells were investigated. It was found that some R-plasmids produce significant variations in adherence and/or hydrophobicity but that these variations show no quantitative or qualitative correlation. PMID- 2883227 TI - Survey of multiply resistant Providencia stuartii in a chronic care unit. AB - Providencia stuartii was cultured over a 4-year period from the urinary tract, throat, perineum, axilla and stools of patients in a long-term chronic care unit, the most common site of colonization being the urinary tract. A total of 17 patients had Prov. stuartii bacteraemia and manipulation of the urinary tract preceded bacteraemia in 10 cases. Eighty-two per cent of the patients had long term urinary tract colonization from 1 month to 4 years. Although most isolates were resistant to all aminoglycosides except amikacin, the organisms were all susceptible to thienamycin, ceftazidime, cefotaxime, ceftizoxime and moxalactam. PMID- 2883228 TI - An outbreak of serious Klebsiella infections related to food blenders. AB - An investigation, including environmental sampling, was undertaken after four leukaemic patients on the same hospital ward developed serious infections with Klebsiella aerogenes, capsular type K14. The source of this organism, common to all four patients, was found to be a food blender used for preparing milk-based drinks on the ward. PMID- 2883229 TI - The formaldehyde/low temperature steam sterilizing procedure. PMID- 2883230 TI - Nosocomial infections with Microsporum canis. PMID- 2883231 TI - The stabilising factors of parasitic infections in Nigeria. AB - The pattern of parasitic infections in Nigeria is discussed taking into consideration the status quo, and factors of change which tend to maintain the present situation rather than improving upon it. These factors include rapid urbanisation and uncontrolled population movement, agricultural developments, socio-economic factors, disease and vector control operations and health care delivery system. This rather deplorable situation calls for increased awareness on the part of everybody such that cognisance is taken of the hazards and remedies of these factors of change in order not to jeopardise our laudable development programmes. PMID- 2883232 TI - Efficacy of Czechoslovak and Soviet Bacillus thuringiensis (serotype H-14) formulations against mosquito larvae. AB - Laboratory and field comparisons were made with two wettable powder formulations of Bacillus thuringiensis serotype H-14 (B. t. H-14) prepared in Czechoslovakia ("Moskitur") and the USSR ("Baktokulicid"). Expressed in the international Aedes aegypti toxic units (TU X mg-1) the potency of these two test formulations was greater than that of the Institute Pasteur Standard IPS-78 (= 1,000 TU X mg-1), i.e. Moskitur had a potency of about 1,500 TU X mg-1 and the Soviet Baktokulicid 2,000 TU X mg-1. The Baktokulicid and Moskitur LC 90 values for laboratory-reared Aedes aegypti larvae were, respectively, 0.11 and 0.16 mg X l-1. The range of LC 90 values for the Czechoslovak wild-caught mosquito species of the genera Aedes and Culex was 0.14-0.31 mg X liter-1 with Moskitur, 0.11-0.41 mg X l-1 with Baktokulicid, and 0.16-0.48 mg X l-1 with IPS-78. The susceptibility of laboratory Anopheles stephensi larvae was close to that of Aedes aegypti, larvae of An. messeae required many times as much Baktokulicid (1.6 mg X l-1) and Moskitur (more than 6.4 mg X l-1) for 90% mortality as did other mosquito species. The aim of outdoor assays was to establish the minimum Moskitur and Baktokulicid rates giving a 100% control of mosquito larvae. For Ae. cantans breeding habitat in flood plain forest areas these rates ranged between 0.1-0.5 mg X l-1 (0.2-1.0 kg X ha-1), for Ae. vexans control on artificially irrigated meadows between 0.8-2.0 mg X l-1 (1.2-3.0 kg X ha-1). Consistently with laboratory bioassays, Baktokulicid gave 100% control of An. messeae 4th instar larvae at a dose as high as 3.2 mg X l-1, Moskitur gave 23.1% kill at 6.4 mg X l 1. The effect of Moskitur and Baktokulicid formulations was immediate, larvae that hatched 7-14 days posttreatment survived. The efficacy of B. t. H-14 outdoor treatments tended to markedly decrease with the larval densities exceeding 100 larvae per 1 dm2. Species of nontarget aquatic organisms, including the Diptera Chaoborus crystallinus, Mychlonyx sp. and Dixidae, were not noticeably affected by treatments with B. t. H-14 formulations used. PMID- 2883233 TI - Induction of protective immunity to experimental hepatic amoebic infection in hamsters. AB - Immunisation of hamsters with the Sephadex G-200 chromatographed Fraction-I of the crude amoebic extract afforded protection in 58% of the animals against an intrahepatic challenge with a virulent subline of axenic Entamoeba histolytica NIH-200 (V). The protected animals had variable levels of anti-FI antiamoebic antibodies, while none of the infected controls had such antibodies. Findings suggest that chromatographed FI of crude amoebic extract might function as a potent immunogen affording protection in amoebic infection. PMID- 2883234 TI - The interleukin 1 gene is expressed by rat glomerular mesangial cells and is augmented in immune complex glomerulonephritis. AB - Cultured rat mesangial cells have features of immune effector cells that may contribute to the derangements in glomerulonephritis. Recent reports have demonstrated that mesangial cells produce a cytokine similar to interleukin 1 (IL 1). We predicted rat mesangial cells could express a gene homologous to murine macrophage IL 1. Mesangial cells were cultured by explant and were used in the fourth through sixth passages. Antibodies to desmin and fibronectin but not cytokeratin stained the cytoskeleton of all mesangial cells examined; no Ia+, leukocyte common antigen+ mononuclear phagocytes were present. RNA from mesangial cells and P388D macrophages hybridized in dot blots with a 32P-probe nick translated from the murine IL 1 cDNA. Mesangial cells but not Swiss 3T3 fibroblasts contained IL 1 mRNA transcripts that co-migrated with the 2.0 kb message from murine P388D macrophages by Northern analysis of poly(A) RNA. In situ hybridization of cultured cells demonstrated specific hybridization of 3H-IL 1 probe to cells with the morphology of contractile mesangial cells and P388D cells but not 3T3 cells. IL 1 release is an important mediator of local inflammation and injury. Therefore we compared the expression of the IL 1 gene in total RNA from kidneys of rats with immune complex glomerulonephritis with that extracted from kidneys of healthy rats. Glomerulonephritic kidneys contain a twofold to threefold increase in IL 1 mRNA compared with normals. We conclude that rat mesangial cells express mRNA with significant homology to murine macrophage IL 1 mRNA and further suggest that local production of the potent phlogistic mediator IL 1 may be important in the pathogenesis of glomerulonephritis. PMID- 2883236 TI - Lack of dendritic Thy-1+ epidermal cells in mice with severe combined immunodeficiency disease. AB - C.B-17 scid (severe combined immunodeficiency disease) mice were used to evaluate the relationship of dendritic Thy-1+ epidermal cells (EC) to T lymphocytes (deficient in scid) and to NK cells (replete in scid). Epidermis from scid mice was deficient in dendritic Thy-1+ cells as determined by immunofluorescent staining of epidermal whole mounts. Similarly, epidermal cell suspensions from scid mice failed to proliferate in response to Con A, as compared with epidermal cell suspensions from C.B-17 control mice. Transplantation of normal bone marrow into scid mice reconstituted morphologically identifiable dendritic Thy-1+ EC in whole mounts, as well as Con A responsiveness of EC suspensions, thus indicating that the deficiency in dendritic Thy-1+ EC in scid mice is at the precursor level. These studies demonstrate that Thy-1+ EC are more closely related to T lymphocytes than to NK cells. PMID- 2883235 TI - Production of interleukin 1 by adult T cell leukemia (ATL) cell lines. AB - The accessory function for T cell activation and the production of interleukin 1 (IL 1) of adult T cell leukemia (ATL) cell lines were studied in vitro. ATL cell lines such as Hut-102, MT-1, and MT-2 functioned as accessory cells for the stimulation of human T cell proliferative response induced with concanavalin A (Con A) and induced allogeneic mixed lymphocyte reaction. Cell lysates of three ATL cell lines and the culture supernatant of MT-2 cells had activities to stimulate murine thymocyte proliferative response. Then we studied physicochemical properties of the factors produced by MT-2 cells. The m.w. of the factors were approximately 15,000 by Sephacryl S-200 column chromatography, and their isoelectric point values were 5.4 and 4.8 by chromatofocussing technique. No fraction contained interleukin 2 (IL 2) activities to stimulate IL 2-dependent murine cytotoxic T cell line. The thymocyte-stimulating activities of the factors were absorbed with rabbit anti-IL 1 alpha antiserum, but not with anti-IL 1 beta antiserum. Furthermore, messenger RNA extracted from MT-2 cells hybridized to complementary DNA of IL 1 alpha, but not of IL 1 beta, by Northern blot hybridization analysis. The factors from MT-2 cells could stimulate the production of IL 2 and the expression of IL 2 receptors of human T cells in the presence of Con A as well as recombinant IL 1 alpha and IL 1 beta did, and these activities were also blocked by rabbit anti-IL 1 alpha antiserum, but not by anti IL 1 beta antiserum. These results suggest that the factors produced by MT-2 cells correspond to IL 1 alpha. However, the accessory function of MT-2 cells for T cell activation was not blocked by rabbit anti-IL 1 antiserum. These results suggest that ATL cell lines produce IL 1-like factors, but the accessory function of ATL cell lines for T cell activation is mediated by some other mechanisms rather than by secreted IL 1-like factors. PMID- 2883238 TI - Epidemiology of human T cell leukemia virus type I infection in East Sepik Province, Papua New Guinea. AB - A serological survey of 317 healthy residents of rural Papua New Guinea (PNG) showed a 26% prevalence of antibodies to human T cell leukemia virus type I (HTLV I). Antibody to HTLV-I was detected in 16% of children less than or equal to 10 years old (including an 18-month-old child) and increased to greater than or equal to 24% in subjects greater than 20 years old. Prospective examination for antibody in 104 residents of one village revealed a seroconversion rate of 13% over a one-year period. The mean titer of antibody in these subjects (1:183) was lower (P less than .0005) than that in persons who were persistently seropositive (1:718). Analysis for clustering of infected subjects suggested that personal contact within the home played a role in the horizontal spread of HTLV-I. These data indicate that HTLV-I infection has a higher prevalence in PNG than in other endemic parts of the world, exposure occurs at an early age, and infection and/or seroconversion is common in adults as well as in children. PMID- 2883237 TI - Heterogeneity in response to interleukin 2 and interleukin 2-producing ability of adult T cell leukemic cells. AB - To examine the possibility of heterogeneous mechanisms in the proliferation of adult T cell leukemia (ATL) cells, leukemic cells from 13 patients, nine acute type and four chronic-type ATL, were examined for the production of interleukin 2 (IL 2) with or without mitogenic stimulation and their response to recombinant IL 2 when exogeneously added. The leukemic cells were classified into four groups, as follows. Group 1 (two patients): Cells of this group produced IL 2 messenger RNA, secreted IL 2, and proliferated when cultured in mitogen-free medium. The spontaneous proliferation of the cells in mitogen-free medium was inhibited by anti-Tac/IL 2 receptor and anti-IL 2 monoclonal antibodies. Moreover, the thymidine incorporation by the cells was enhanced in response to exogeneously added recombinant IL 2 and IL 2 produced by themselves. These results indicate that the ATL cells of this group proliferate with autostimulation by IL 2. Group 2 (seven patients): Cells of this group did not secrete IL 2 when cultured in mitogen-free medium, but the cells showed response to exogeneously added recombinant IL 2 and proliferated in culture. These results indicate that the ATL cells of this group proliferate by a paracrine mechanism. Group 3 (one patient): Cells of this group secreted IL 2 in mitogen-free medium. However, the spontaneous proliferation of these cells in vitro was very low, and the response to recombinant IL 2 was also very low. Group 4 (three patients): Cells of this group did not secrete IL 2 in mitogen-free medium. Spontaneous proliferation and the response to recombinant IL 2 were also very low. The clinical feature of all patients of Groups 1 and 2 was acute-type, and that of Groups 3 and 4 was chronic type. Thus, we conclude that heterogeneous mechanisms exist in the proliferation of leukemic cells, and that growth rate in mitogen-free medium and response to IL 2 of the cells may have a significant relationship to the clinical feature, acute or chronic-type. PMID- 2883239 TI - Use of erythromycin to prevent pertussis in newborns of mothers with pertussis. AB - During the period 1975-1985, 35 women with serology- or culture-confirmed pertussis at the time of labor were admitted to the Danderyd Hospital (Danderyd, Sweden). In 32 cases, the mothers were allowed to nurse their newborns while receiving erythromycin therapy. Erythromycin prophylaxis was given to 28 newborns. None of the newborns developed clinical or laboratory signs of whooping cough. The therapy was well tolerated by the newborns and did not affect the microflora in the gut. Maternal antibodies to pertussis toxin and to the filamentous hemagglutinin were found in cord blood, and levels decreased during the follow-up period. The study demonstrated that mothers with pertussis can safely be allowed to nurse their infants if both receive erythromycin. PMID- 2883240 TI - Evidence of serum antibodies to Neisseria gonorrhoeae before gonococcal infection. AB - To characterize the serum antibody response to urethral infection with Neisseria gonorrhoeae, we examined pre- and postinfection sera from 13 men experiencing their first gonococcal infection. Using western blot analysis, we found that nine of 13 patients developed new serum IgG antibodies against one or more antigens, most commonly against lipooligosaccharide, followed in order by the H.8-antigen, pili, proteins I and II, and protein III. Twelve of 13 patients had preexisting IgG to gonococcal antigens, most commonly against the H.8 antigen, followed by pili, lipooligosaccharide, protein I, and protein III. Using serum obtained from other patients before and after nasopharyngeal carriage of Neisseria meningitidis, we demonstrated that carriage resulted in serum IgG cross-reactive to N. gonorrhoeae antigens. This is likely explanation for the presence of antigen-specific antibody in preinfection sera. PMID- 2883241 TI - [Serotype and drug susceptibility of Bordetella pertussis and Bordetella parapertussis isolated from 1975 to 1985 in Japan]. PMID- 2883242 TI - [Platelet factor XIII as the collagen receptor]. PMID- 2883243 TI - [Papillary adenocarcinoma of the thyroid followed by manifestation of multiple endocrine neoplasia (MEN) type I: a retrospective study of patient's data in the past 11 years and histological studies of the thyroid, parathyroid, and pancreatic islet]. PMID- 2883245 TI - [A case of suspected allergic granulomatous angiitis following surgery of Sipple's syndrome]. PMID- 2883246 TI - [Adult T cell lymphoma with massive gastric involvement--a case report]. PMID- 2883244 TI - [A correlation between the concentrations of serum T4 and the values for TSH binding inhibiting antibody (TBIAb) during the clinical course of a patient with hashitoxicosis]. PMID- 2883248 TI - Effect of dietary alpha-linolenate/linoleate balance on brain lipid compositions and learning ability of rats. AB - Spontaneously hypertensive rats (SHR) and normotensive control, Wistar/Kyoto (WKY) rats through two generations were fed a semipurified diet supplemented either with safflower oil (rich in linoleate) or with perilla oil (rich in alpha linolenate). The cerebral lipid contents and phospholipid compositions did not differ between the two dietary groups of SHR rats. There were also no differences in the unsaturated/saturated ratios of individual phospholipids or the proportions of plasma-logens. However, the proportions of (n-3) and (n-6) fatty acids were significantly different. Decreases in the proportions of docosahexaenoate [22:6 (n-3)] in phosphatidylethanolamine and phosphatidylserine in the safflower oil group were compensated for with increases in the proportions of docosatetraenoic [22:4 (n-6)] and docosapentaenoic [22:5 (n-6)] acids as compared with the perilla oil group. These differences in phospholipid acyl chains were much smaller than the difference in the proportions of linoleate and alpha-linolenate of the diets. In a brightness-discrimination learning test, the total number of responses to the positive and negative stimuli were less in the groups fed perilla oil. However, the alpha-linolenate-deficient group took longer to decrease the frequency of R- responses and therefore longer to learn the discrimination. Consequently, the correct response ratios were higher in the perilla oil groups than in the safflower oil groups. Thus, the dietary alpha linolenate/linoleate balance influenced the (n-3)/(n-6) balance of polyenoic fatty acids differently among brain phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883247 TI - Induction of tissue transglutaminase in human peripheral blood monocytes by intracellular delivery of retinoids. AB - Human peripheral blood monocytes (HPBM) from normal donors, isolated by counter current centrifugal elutriation into two subpopulations, showed no significant difference in their ability to differentiate in vitro into macrophages as determined by induction of a protein cross-linking enzyme tissue transglutaminase (TGase). The two subpopulations were equally responsive to the augmenting effect of recombinant interferon-gamma (rIFN-gamma) on expression of tissue TGase. In vitro maturation and treatment with rIFN-gamma of HPBM were associated with increased binding of tritiated retinol. Intracellular delivery of retinol rendered this hormone active in inducing the differentiation of HPBM. The retinoid-induced expression of tissue TGase was the result of increased accumulation of the enzyme peptide and not activation of preexisting enzyme. We propose, therefore, that maturation of HPBM, induced by in vitro culture or treatment with rIFN-gamma, is associated with acquisition of cell surface receptors for serum retinol-binding protein. PMID- 2883249 TI - The relationship of thyroid antibodies to the postpartum recurrence of hyperthyroidism in Graves' disease. PMID- 2883250 TI - An adenovirus type 3 host range variant with mutations in the E1a and E3 early gene regions. AB - A spontaneous variant of adenovirus (Ad) type 3 (subgroup B) was identified, which did not grow in HeLa cells, but grew in 293 cells with a large plaque morphology. The variant (Ad3var100) had a defect in the the early gene region E1a; it could grow in cells that supplied E1a functions and was complemented for growth in HeLa cells by Ad5 wild-type (subgroup C) but not by the E1a deletion mutant Ad5d1312. It also bore a deletion of some 1.5 kb in the E3 region. The loss of these sequences conferred on the variant the ability to inhibit Ad5 wild type virus, although Ad3 wild-type was dominant over the variant. No transdominance was seen between wild-type Ad3 and Ad5. The E1a mutation was placed in a wild-type background and this E1a mutant had the host range properties of the variant, but did not retain the large plaque morphology and was not dominant over Ad5. The E3 mutation was separated from the E1a lesion by marker rescue; the resulting E3 mutant retained dominance over Ad5, grew in HeLa cells and had a plaque morphology intermediate between wild-type and variant. PMID- 2883251 TI - Genomic heterogeneity of equine betaherpesviruses. AB - The genomes of 51 isolates of slowly cytopathic equine herpesviruses were examined by digestion with restriction endonucleases. Forty-seven of the isolates showed considerable fragment pattern heterogeneity although common fragments were evident, especially when any two isolates were compared or when they were digested with SalI. Fifteen of the 47 viruses, selected for their diverse fragment patterns, showed a high degree of homology in Southern blot hybridization. In contrast, four viruses, representing three epidemiologically distinct isolations, shared few, if any, comigrating fragments with the 47 equine herpesvirus 2 (EHV-2) isolates, although they shared comigrating fragments with each other. These four viruses showed reduced homology to a representative EHV-2 isolate by Southern blot hybridization under stringent conditions. Although not sharply delineated from EHV-2, these four viruses grew very slowly and had low yields in vitro, and preliminary data suggested they had a significantly smaller genome than EHV-2 (148 +/- 12 kb compared to 190 kb). These four viruses may be prototypic of a novel equine betaherpesvirus. PMID- 2883252 TI - Sequence analysis of the matrix protein gene of human parainfluenza virus type 3: extensive sequence homology among paramyxoviruses. AB - The sequences of the human parainfluenza virus type 3 (PIV3) matrix (M) mRNA [1150 nucleotides exclusive of poly(A)] and predicted M protein (353 amino acids) were determined by sequence analysis of cloned cDNA and viral genomic RNA. The gene-end sequence of the M gene differed from the semi-conserved gene-end sequence of the other PIV3 genes by an apparent insertion of eight nucleotides. The PIV3 M protein shared high sequence homology with Sendai virus and moderate homology with measles virus and canine distemper virus. Statistical analysis of the available sequences showed that the M protein was the most highly conserved parainfluenza viral protein. PMID- 2883253 TI - The regulation of neurite outgrowth, growth cone motility, and electrical synaptogenesis by serotonin. AB - Identified neurons of the buccal ganglion of the snail Helisoma when isolated from their ganglionic environment and plated in cell culture grow new neurites that are tipped with motile growth cones. Addition of the neurotransmitter serotonin to the culture medium surrounding actively growing neurons causes an immediate, premature cessation of neurite elongation in specific identified neurons. Serotonin selectively inhibits neurite extension of neurons B19 and P5 while having no effect on the extension of neuron B5. Coincident with the serotonin evoked inhibition of neurite elongation is an inhibition of growth cone motile activities and a retraction of growth cone filopodia and lamellipodia. One site of serotonin's growth inhibitory actions is directly at the growth cone rather than at the neurites or cell body. A second area of this study concerns connectivity. In Helisoma neurons the formation of electrical synaptic connections critically relies on both potential partner neurons having a mutual interaction of actively growing neurites. Neurons in a nongrowing state do not form electrical synapses (Hadley et al., 1983). As a result of inhibiting neurite extension, serotonin is able to affect synaptogenesis by preventing certain neurons (neurons B19) from forming electrical synaptic connections with other neurons (neurons B5) that are themselves competent to interconnect. Thus, by inhibiting neurite extension, serotonin is capable of regulating both the development of arborizations and the formation of connectivity. PMID- 2883254 TI - Identification and characterization of an N-methyl-D-aspartate-specific L [3H]glutamate recognition site in synaptic plasma membranes. AB - Conditions have been developed for an L-[3H]glutamate binding assay in which 85 95% of the specific binding is to a site that corresponds to the N-methyl-D aspartate subclass of acidic amino acid receptors. Incubation of synaptic plasma membranes with L-[3H]glutamate in 50 mM Tris/acetate, pH 7.4, for 2-20 min at 2 degrees C results in binding with pharmacological characteristics of the electrophysiologically defined N-methyl-D-aspartate receptor. The fraction of glutamate binding to this subclass of receptors, relative to the total, decreases with both increased time and temperature. This binding is reversible, is concentrated in the synaptic plasma membrane fraction, has a pH optimum of 7.0 7.4, and is linear with respect to tissue protein concentration. The binding is unaffected by 1 mM concentrations of the anions sulfate, chloride, bromide, thiocyanate, phosphate, acetate, nitrate, or carbonate and the monovalent cations potassium or ammonium. However sodium and the divalent cations copper, cobalt, zinc, cadmium, and manganese decrease binding to this N-methyl-D-aspartate site. PMID- 2883255 TI - A novel chloride-dependent L-[3H]glutamate binding site in astrocyte membranes. AB - Membrane fractions prepared from astrocytes grown in culture exhibit a specific binding site for L-[3H]glutamate that is Cl--dependent and Na+-independent. The binding site is a single saturable site with a KD of about 0.5 microM, is inhibited by L-aspartate, L-cysteate, and quisqualate, and is insensitive to kainate, N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate, and 2-amino-4-phosphonobutyrate. The pharmacological characteristics of the binding site indicate that it is distinct from any site previously described in synaptic membrane preparations. Comparisons of ionic requirements, ligand specificity, and inhibitor sensitivities, however, suggest the described binding is the first step in a Cl--dependent high-affinity glutamate uptake system. Such binding studies provide a useful model system in which to investigate the close association between excitatory amino acids, astrocytes, the termination of glutamate's excitatory action by high-affinity uptake, and the excitotoxic action of acidic amino acids in membranes of a single cell type. PMID- 2883256 TI - Calcium dependence of muscarinic receptor-mediated catecholamine secretion from the perfused rat adrenal medulla. AB - It had previously been thought that muscarinic cholinergic receptors utilize an influx of extracellular calcium for activation of adrenomedullary catecholamine secretion. However, it has recently been demonstrated that muscarinic receptors on isolated adrenal chromaffin cells can elevate cytosolic free calcium levels in a manner independent of extracellular calcium, presumably by mobilizing intracellular calcium stores. We now demonstrate that muscarinic receptor mediated catecholamine secretion from perfused rat adrenal glands can occur under conditions of extracellular calcium deprivation that are sufficient to block both nicotine- and electrically stimulated release. Three independent conditions of extracellular calcium deprivation were used: nominally calcium-free perfusion solution (no calcium added), EGTA-containing calcium-free perfusion solution, and perfusion solution containing the calcium channel blocker verapamil. Secretion was evoked from the perfused glands by either transmural electrical stimulation or injection of nicotine or muscarine into the perfusion stream. Each condition of calcium deprivation was able to block nicotine- and electrically stimulated catecholamine release in an interval that left muscarine-evoked release largely unaffected. The above results demonstrate that muscarine-evoked catecholamine secretion from perfused rat adrenal glands can occur in the absence of extracellular calcium, presumably by mobilization of intracellular calcium. The latter may be due to muscarinic receptor-mediated generation of inositol trisphosphate. PMID- 2883257 TI - Acetylcholinesterase from the skeletal muscle of the lamprey Petromyzon marinus exists in globular and asymmetric forms. AB - To obtain information about the evolution of acetylcholinesterase (AChE), we undertook a study of the enzyme from the skeletal muscle of the lamprey Petromyzon marinus, a primitive vertebrate. We found that the cholinesterase activity of lamprey muscle is due to AChE, not pseudocholinesterase; the enzyme was inhibited by 1,5-bis(4-allyldimethylammonium phenyl) pentane-3-one (BW284C51), but not by tetramonoisopropyl pyrophosphortetramide (iso-OMPA) or ethopropazine. Also, the enzyme had a high affinity for acetylthiocholine and was inhibited by high concentrations of substrate. A large fraction of the AChE was found to be glycoprotein, since it was precipitated by concanavalin A-agarose. Optimal extraction of AChE was obtained in a high-salt detergent-containing buffer; fractional amounts of enzyme were extracted in buffers lacking salt and/or detergent. These data suggest that globular and asymmetric forms of AChE are present. On sucrose gradients, enzyme that was extracted in high-salt detergent-containing buffer sedimented as a broad peak of activity corresponding to G4; additionally, there was usually a peak corresponding to A12. Sequential extraction of AChE in conjunction with velocity sedimentation resolved minor forms of AChE and revealed that the G1, G2, G4, A4, A8, and A12 forms of AChE could be obtained from the muscle. The identity of the forms was confirmed through high-salt precipitation and collagenase digestion. The asymmetric forms of AChE were precipitated in low ionic strength buffer, and their sedimentation coefficients were shifted to higher values by collagenase digestion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883258 TI - Mass fragmentographic determination of gamma-aminobutyric acid and glutamic acid in discrete amygdaloid nuclei of rat brain. AB - A mass fragmentographic method for the simultaneous quantification of gamma aminobutyric acid (GABA) and glutamic acid is described. In a convenient one-step reaction, the two amino acids were derivatized with pentafluoropropionic anhydride and pentafluoropropanol. The derivatization products were stable for several days. The technique has been applied to the assay of GABA and Glu in five amygdaloid nuclei of the rat brain. The GABA level was high in the central and medial nuclei, whereas the Glu level was high in the lateral and basal nuclei. The regional distribution of GABA was different from that of Glu within the amygdaloid nuclei. PMID- 2883259 TI - High-affinity transport of gamma-aminobutyric acid, glycine, taurine, L-aspartic acid, and L-glutamic acid in synaptosomal (P2) tissue: a kinetic and substrate specificity analysis. AB - In a cortical P2 fraction, [14C]gamma-aminobutyric acid ([14C]GABA), [14C]glycine, [14C]taurine, and [14C]glutamic and [14C]aspartic acids are transported by four separate high-affinity transport systems with L-glutamic acid and L-aspartic acid transported by a common system. GABA transport in cortical synaptosomal tissue occurs by one high-affinity system, with no second, low affinity, transport system detectable. Only one high-affinity system is observed for the transport of aspartic/glutamic acids; as with GABA transport, no low affinity transport is detectable. In the uptake of taurine and glycine (cerebral cortex and pons-medulla-spinal cord) both high- and low-affinity transport processes could be detected. The high-affinity GABA and high-affinity taurine transport classes exhibit some overlap, with the GABA transport system being more specific and having a much higher Vmax value. High-affinity GABA transport exhibits no overlap with either the high-affinity glycine or the high-affinity aspartic/glutamic acid transport class, and in fact they demonstrate somewhat negative correlations in inhibition profiles. The inhibition profiles of high affinity cortical glycine transport and those of high-affinity cortical taurine and aspartic/glutamic acid transport also show no significant positive relationship. The inhibition profiles of high-affinity glycine transport in the cerebral cortex and in the pons-medulla-spinal cord show a significant positive correlation with each other; however, high-affinity glycine uptake in the pons medulla-spinal cord is more specific than that in the cerebral cortex. The inhibition profile of high-affinity taurine transport exhibits a nonsignificant negative correlation with that of the aspartic/glutamic acid transport class. PMID- 2883260 TI - Evidence for somatostatin-containing fibers projecting from the pallidal complex to the striatum of the rat. AB - The origin of afferent somatostatin-containing fibers terminating in medial and ventral parts of the striatum has been investigated by performing various neurochemical and surgical lesions in the rat. Lesions of the anterior hypothalamus, amygdala, and the hippocampal commissure as well as lesions with 6 hydroxydopamine and 5,7-dihydroxytryptamine failed to decrease striatal somatostatin levels. However, thermal coagulation of the globus pallidus or knife cut lesions performed ventrally to the striatum resulted in significant decreases in striatal somatostatin content. Analysis of the topographical distribution of somatostatin within the striatum after thermal lesions of the globus pallidus as well as after kainic acid-induced seizures revealed a preferential loss of the peptide in medial and ventral portions of the striatum, the site of terminating afferent somatostatin nerve fibers. The data suggest that the striatal afferent somatostatin-containing neurons may originate in the area of the globus pallidus. PMID- 2883261 TI - Effect of N-methyl-4-phenylpyridinium ion on monoamine oxidase in a clonal rat pheochromocytoma cell line, PC12h. AB - The effects of the neurotoxin N-methyl-4-phenylpyridinium ion (MPP+) on the enzymes involved in synthesis and catabolism of catecholamines were examined using a clonal rat pheochromocytoma cell line, PC12h, as a model of dopaminergic neurons. MPP+ added in the culture medium was found to be accumulated in PC12h cells after 30-min incubation. Monoamine oxidase (MAO) activity in PC12h cells was inhibited by MPP+ in a dose-dependent way from 10 nM to 10 microM, but concentrations of MPP+ higher than 100 microM were found to increase the MAO activity. At the lower concentrations MPP+ inhibited MAO noncompetitively with respect to the substrate, kynuramine, and at the higher concentrations it increased both the Km and the Vmax values of MAO toward the substrate. On the other hand, tyrosine hydroxylase activity and the dopamine concentrations in PC12 cells were not changed by incubation with MPP+ for 30 min, 60 min, or 24 h. PMID- 2883262 TI - Clostridium perfringens brain infection following a penetration wound of the orbit. PMID- 2883263 TI - The dementia of Alzheimer's disease: an update. PMID- 2883264 TI - Multiple endocrine neoplasia type IIb: a description of several patients and review of the literature. AB - Our experience exemplifies the varied clinical presentations of patients with MEN IIb. This syndrome may be familial or sporadic, and clinical stigmata may be identifiable in infancy, particularly the characteristic facies and the appearance of ganglioneuromas. First-degree relatives of affected propositi and individuals with other stigmata of the syndrome should be screened carefully and repeatedly for both medullary thyroid carcinoma and pheochromocytoma. The availability of sensitive screening tests may permit detection of C-cell hyperplasia of the thyroid and adrenal medullary hyperplasia before the development of malignancy or hemodynamic consequences of pheochromocytoma. Early detection of these thyroid and adrenal disorders will permit early surgical intervention. PMID- 2883266 TI - Regional heterogeneity in the distribution of somatostatin-28- and somatostatin 28(1-12)-immunoreactive profiles in monkey neocortex. AB - The distribution of the prosomatostatin-derived peptides (PSDP), somatostatin-28 and somatostatin-28(1-12), in the cynomolgus monkey (Macaca fascicularis) neocortex was characterized in quantitative immunohistochemical studies of 3 visual areas (V1, primary visual cortex; V2, the adjacent visual association area; and AIT, a visual association area in anterior inferior temporal cortex), 2 auditory areas (AI, primary auditory cortex; and T1, an adjacent auditory association area) and anterior cingulate cortex (Area 24). The results of similar quantitative analyses in 3 homologous areas in rat neocortex (primary visual, primary auditory, and anterior cingulate) are also presented. Primate cortical areas differed significantly in both density and laminar distribution of PSDP immunoreactive profiles. Area 24, the most densely labeled area, had nearly 6 times as many PSDP-immunoreactive neurons as V1. Both auditory areas contained approximately two-thirds the number of PSDP-immunoreactive neurons found in Area 24; however, both had nearly 4 times as many immunoreactive neurons as V1. The 3 visual areas showed incremental increases in the number of PSDP-immunoreactive neurons; V2 contained nearly twice and AIT nearly 3 times the number of immunoreactive neurons present in V1. Both the supra- and infragranular layers were densely labeled in Area 24 and Area T1, however, in AI, V1, V2, and AIT the infragranular layers were relatively sparsely labeled. In contrast to the regional heterogeneity found in the primate neocortex, the distribution of immunoreactive neurons was quite uniform across the 3 rat cortical areas. The rat cortical areas contained substantially fewer immunoreactive neurons than most of the monkey cortical areas, and a majority of these immunoreactive neurons were located in the infragranular layers. These findings suggest that the regional specialization of primate neocortex involves the selective distribution of PSDP immunoreactive neurons. They also suggest that chemically specified intrinsic organization of neocortex is not likely to be uniform across species or across cortical areas in the primate. The distinctive regional distribution patterns of PSDP-immunoreactive profiles appear to parallel that of the long corticocortical projections (contralateral and distant ipsilateral projections), suggesting an association between these presumed inhibitory interneurons and this important extrinsic system. PMID- 2883265 TI - Evidence for transient perinatal glutamatergic innervation of globus pallidus. AB - There is no known glutamatergic innervation of globus pallidus (GP) in adult mammals, but we report that during postnatal development of the GP there are large, transient increases in both presynaptic high-affinity glutamate uptake and postsynaptic Na+-independent glutamate receptor binding. These glutamatergic markers increase rapidly in rat GP after birth and then decrease to adult levels over a period of weeks. A similar developmental pattern of pallidal glutamate binding was found in human brains. In contrast, binding in rat caudate-putamen (CPu) increases after birth, reaches a peak, and remains constant into adulthood. The results suggest that a glutamatergic pathway transiently innervates the globus pallidus during the perinatal period. Because glutamate is an excitotoxin, this pathway may account, in part, for the basal ganglia damage seen in some forms of cerebral palsy after perinatal hypoxia/ischemia. PMID- 2883267 TI - Rat brain 5-HT1C receptors are encoded by a 5-6 kbase mRNA size class and are functionally expressed in injected Xenopus oocytes. AB - Injection of rat brain RNA into Xenopus laevis oocytes induces synthesis of receptors that show an electrophysiological response to bath application of serotonin. While there are at least 4 pharmacologically distinct subtypes of 5-HT binding sites in the rat brain, we find that the pharmacological characteristics of the predominant electrophysiologically active receptor synthesized in Xenopus oocytes are most consistent with those of the 5-HT1C subtype. Additional electrophysiologically active 5-HT receptor types could not be detected. Injection of mRNA isolated from a number of rat brain regions shows that the choroid plexus is particularly enriched for 5-HT1C mRNA. Oocytes injected with RNA isolated from this region respond 16 or 8 times more strongly to serotonin than do oocytes injected with RNA isolated from cortex or substantia nigra, respectively. In addition, by fractionation of rat brain mRNA through agarose gels, we have identified a single RNA size class of about 5-6 kbase that encodes this serotonin receptor. PMID- 2883268 TI - Expression of tyrosine hydroxylase in neurons of cultured cerebral cortex: evidence for phenotypic plasticity in neurons of the CNS. AB - In vivo, neurons of the cerebral cortex of rat embryos did not stain with antibodies to the catecholamine (CA) biosynthetic enzyme tyrosine hydroxylase (TH) even when examined using a highly sensitive technique for radioimmunocytochemistry. However, when embryonic day (E) 13 cortex was grown 1 d in culture, several thousand cells expressed immunoreactive and catalytically active TH. All TH cells simultaneously labeled with the neuronal enzyme, neuronal specific enolase, indicating that the TH was exclusively localized in neurons. Moreover, all TH neurons were postmitotic since they did not incorporate 3H thymidine. With time in culture, the number of TH cells selectively declined from nearly 3000 cells at 2 d to several cells at 14 d. Similarly, the number of neurons competent to express TH in culture declined with advancing age of the donor embryo. Thus, by E18, very few cortical neurons had the capacity to express TH. We conclude that during a critical period of development, postmitotic cerebral cortical neurons can express catecholamine traits in vitro but not in vivo. Thus, the neurotransmitter phenotype of certain classes of central neurons is not fixed but can be influenced by epigenetic factors found in their environment, thereby providing evidence of phenotypic plasticity in the central nervous system (CNS). PMID- 2883269 TI - Depolarization- and transmitter-induced changes in intracellular Ca2+ of rat cerebellar granule cells in explant cultures. AB - Digital imaging of the Ca indicator fura-2 has been used to study the responses of developing granule cells in culture to depolarization and transmitter action. Unstimulated cells bathed in Krebs saline exhibited cytoplasmic Ca ion concentrations, [Ca2+], that were generally in the 30-60 nM range. Exposure of cells to high-potassium (25 mM) saline depolarized the membrane potential and produced an immediate rise in [Ca2+] that recovered within 2-3 min in normal saline. The response grew progressively larger over the first 20 d in culture. Transient increases in [Ca2+] to levels greater than 1 microM were observed after 12-14 d in vitro, at which time the cells displayed intense electrical activity when exposed to high K. At this stage, the increases were attenuated by blocking action potential activity with TTX. In TTX-treated or immature cells, in which the transient phase of the Ca change was relatively small, a second exposure to high K typically produced a much larger Ca response that the initial exposure. The duration of this facilitation of the response persisted for periods longer than 5 min. Application of the neurotransmitter GABA induced a transient increase in membrane conductance, with a reversal potential near resting potential (approx. -60 mV), and caused an intracellular Ca2+ increase that outlasted the exposure to GABA by several minutes. Glutamate, or kainate, induced an increase in membrane conductance but with a reversal potential more positive than spike threshold. These agents also elevated intracellular Ca2+, but unlike the case with GABA, this Ca response reversed rapidly upon removal of the transmitter. The facilitatory effect of repeated exposures to high-K saline, as well as the persistent Ca elevation following a brief GABA application, suggests that granule cells possess the capability of displaying activity-dependent changes in Ca levels in culture. PMID- 2883270 TI - Zinc deficiency in rats reduces the vasodilation response to bradykinin and prostacyclin. AB - The objective of this study was to determine the effect of zinc deficiency on the blood pressure response of rats to intravenously administered doses of two chemically distinct vasodilators, bradykinin (BK) and prostacyclin (PGI2). Immature albino rats were fed a low zinc (less than 1 ppm) diet based on soybean protein, a similar control diet (100 ppm) ad libitum or the control diet, pair fed. After 3 wk, the carotid arteries were catheterized for blood pressure measurement and graded doses of the vasodilators were injected as a bolus into a branch of the femoral vein. In one experiment graded doses (0-8 micrograms/kg body wt) of Bk and in another graded doses (0-400 ng/kg body wt) of PGI2 were injected. In a third experiment the PGI2 doses ranged from 0 to 1000 ng/kg and, in addition to the 3-wk depletion group, two groups were repleted by feeding the control diet for 1 or 4 d. The low zinc diet induced zinc deficiency as evidenced by low rates of gain and low plasma zinc levels and significantly (P less than 0.05) decreased the blood pressure response (Emax) to both BK and PGI2. Pair feeding had no significant effect on the response; the Emax values as determined by double-reciprocal plots of the data were unchanged by the quantity of control diet consumed. Short-term repletion did not restore the PGI2 response to control values. The data are interpreted as suggesting that zinc deficiency impairs the function of vasodilator receptors in the rat vasculature. PMID- 2883271 TI - L-prolyl-L-leucyl-glycinamide analogues--a new class of peptide antihypertensives. AB - Accumulating evidence suggests that there is an increase in the density (maximum binding sites) of striatal dopamine receptors in the central nervous system of spontaneously hypertensive rats (SHR). A tripeptide of hypothalamic origin, PLG (L-Prolyl-L-Leucyl-Glycinamide) has been found to have modulatory effect on the dopamine receptors in the central nervous system of rats. Two analogues of PLG with cyclic amino-acid residues, L-Prolyl-L-Leucyl-(-)-thiazolidine-2-carboxamide and L-Prolyl-L-Leucyl-(+)-thiazolidine-2-carboxamide, have shown antihypertensive effect at the established phase of hypertension in 16-week old SHRs at a dose of 35 mg/kg per day per 7 days i.p. It was also observed from studies of radioligand [3H]-spiroperidol binding that the laevo-isomer of the PLG analogue has down regulated the up-regulated dopamine receptors. Our findings confirm the role of central dopaminergic pathways in the pathogenesis of hypertension in SHR. PMID- 2883272 TI - Verapamil antagonizes forearm vasoconstriction mediated by selective alpha 1- and alpha 2-agonists in hypertensive patients. AB - Calcium channel blocking agents preferentially antagonize alpha 2-mediated pressor responses in various animal species. Whether the same happens in man is not clear. For this reason we studied the interference exerted by verapamil, a calcium entry blocker, on forearm vasoconstriction mediated by selective alpha 1- (methoxamine) and alpha 2- (B-HT 933) adrenergic agonists in untreated mild-to moderately hypertensive patients (n = 22). Each patient underwent a single study. Forearm blood flow was recorded by strain gauge venous plethysmography; all drugs were infused into the brachial artery at systemically ineffective rates. Cumulative dose-response curves to intra-arterial methoxamine or B-HT 933 were obtained during saline or two different rates of verapamil infusion (0.9 and 3.1 micrograms/100 ml forearm tissue per min) which increased forearm blood flow dose dependently without changing systemic blood pressure or heart rate. Either methoxamine or B-HT 933 decreased forearm blood flow during saline infusion, but their effect was blunted in a dose-dependent manner during verapamil. No evidence of preferential alpha 2-antagonism was present. At variance with animal data, calcium entry blockade by verapamil antagonizes either alpha 1- or alpha 2 mediated vasoconstriction in human forearm vessels. PMID- 2883273 TI - Terazosin: a new alpha 1-blocker for the treatment of hypertension: a review of randomized, controlled clinical trials of once-daily administration as monotherapy. AB - Terazosin, a new selective long-acting alpha1-adrenergic blocking agent, has been shown to be an effective once-daily antihypertensive agent in four of five randomized double-blind placebo-controlled studies of patients with mild to moderate hypertension. In one trial, 24-h monitoring revealed that terazosin produced a sustained blood pressure lowering effect throughout the day. In three fixed-dose trials, steady patterns of blood pressure response during maintenance therapy indicated that tolerance to terazosin did not develop. Favourable changes in the plasma lipid profile were observed, while laboratory data suggested the development of haemodilution. Overall, terazosin was well tolerated. Asthenia, dizziness and peripheral oedema were significantly more common in patients treated with terazosin than with placebo. PMID- 2883274 TI - Somatostatin limits rise in glomerular filtration rate after a protein meal. AB - To evaluate the glomerular filtration rate (GFR) response to a protein meal in patients with diabetes and to study the role of glucagon and growth hormone, we studied inulin clearance for three 30-minute periods before and 3 hours after an 80 g protein meal in seven healthy volunteers and 10 patients with diabetes. Patients with diabetes were chosen because their renal response to such a meal has been reported to be abnormal. All had an increase in GFR and plasma glucagon levels after the protein meal. The peak rise in GFR occurred from 1 to 2 1/2 hours after the meal (mean +/- SEM, delta 26 +/- 5 mL/min/m2, controls; delta 22 +/- 7 mL/min/m2, patients with diabetes), with the mean time to normal rise in GFR occurring at 2 hours after the meal. Similarly, plasma glucagon values peaked at different times in individual patients (delta 769 +/- 532 pg/mL, controls; delta 267 +/- 69 pg/mL, patients with diabetes), with the mean plasma glucagon rise occurring 1 hours after the meal. Premeal growth hormone levels tended to be higher in the patients with diabetes (7.6 +/- 1.4 vs 2.1 +/- 0.4 ng/mL), and did not change after the meal. To allow study of the contribution of the increased plasma glucagon to the rise in GFR, eight of these patients (five with diabetes) volunteered to undergo a second GFR response test with a simultaneous infusion of somatostatin. The glucagon response was significantly lowered at all time periods during the infusion (P less than 0.05); no significant change in growth hormone occurred. Without somatostatin in these eight patients, peak increase in postmeal GFR average 20.6 +/- 1.5 mL/min/m2; with the somatostatin, peak increase in GFR was 6.0 +/- 1.8 mL/min/m2 (P less than 0.01). Neither metabolic control nor degree of albuminuria was significantly different at the time of the two studies. Thus, as has been shown in animals, somatostatin infusion limits the rise in GFR after a protein meal in humans. PMID- 2883275 TI - Evidence for central alpha2-adrenergic mechanism of clonidine-induced ejaculatory disturbance in dogs. AB - In order to clarify the central mechanism of clonidine (CL)-induced sexual dysfunction such as erectile and ejaculatory disturbances, we examined the effects of intracerebroventricularly (i.c.v.) administered CL on erection and ejaculation in male dogs. CL (0.5-5 micrograms/kg) produced a dose-related inhibition of ejaculation but not significant inhibition of erection by the manual stimulation of the penis. Sperm was not found in the urine drawn from the urinary bladder, suggesting that the inhibitory effect of CL on ejaculation was not due to retrograde ejaculation. The ejaculatory disturbance elicited by CL (5 micrograms/kg) was antagonized by an alpha 2-adrenoceptor antagonist, yohimbine (1-10 micrograms/kg, i.c.v.) in a dose-related manner. In contrast to the effect of yohimbine, it was unaffected by an alpha 1-adrenoceptor antagonist, prazosin (3 and 10 micrograms/kg, i.c.v.). These results indicate that i.c.v. administered CL may selectively inhibit the ejaculatory response, which is presumably mediated through the stimulation of alpha 2-adrenoceptors. PMID- 2883276 TI - Isomeric octopamines: their occurrence and functions. PMID- 2883278 TI - The angle of internal flow as an indicator of filling and drug release properties of capsule formulations. AB - The cohesiveness of size fractions of acetylsalicylic acid and lactose alone and in various combinations has been determined by estimation of the rate of decrease in volume as a function of tamping under standard conditions. The cohesiveness was quantified in terms of empirically derived characteristic, the angle of internal flow phi. The value of phi was found to decrease with the particle size of acetylsalicylic acid, but not lactose, and was found to be dependent on the relative proportion and particle sizes of acetylsalicylic acid and lactose when blends of powder were studied. The value of the time for 50% of the drug content to be released from a hard gelatin capsule in an in-vitro dissolution test, T50, was found to decrease with decreasing values of omega for capsules containing acetylsalicylic acid alone. For capsules containing powder blends there was no consistent relationship between the value of T50 and phi. PMID- 2883277 TI - Stability of insulin mixtures in disposable plastic insulin syringes. AB - The miscibility of short and long acting porcine, human and bovine insulins has been investigated using HPLC. Soluble insulin is rapidly lost from solution when mixed with both isophane and zinc insulin, although the mechanism may be different in these two cases. The time for up to 50% or more to be lost is often less than 2 min. The percentage lost is dependent upon the ratio of the mixture and the type and origin of the insulin. In the case of soluble: zinc mixtures it is greatest for porcine and least for bovine, in the case of soluble: isophane mixtures it was least for human and greatest for bovine. The greater the original amount of soluble insulin present the less the loss. The results help explain recent clinical reports that mixtures of soluble and zinc insulins fail to achieve satisfactory control of post-prandial blood sugar levels. PMID- 2883279 TI - Effects of glucagon on cAMP accumulation and ketogenesis in hepatocytes from euthyroid and hypothyroid rats. AB - The resistance to the effects of glucagon was studied in isolated hepatocytes prepared from male rats treated with 6N-propyl-2-thiouracil (PTU). Incorporation of [14C]oleate into ketone bodies in response to various concentrations of glucagon (10(-5) to 10(-10) M) was reduced in hepatocytes from hypothyroid rats compared with the euthyroid group. The reduced sensitivity to the effects of glucagon on ketogenesis after treatment with PTU was associated with a reduced ability of those hepatocytes to maintain cyclic adenosine-3',5'-monophosphate (cAMP) at levels required to stimulate ketogenesis. The concentration of cAMP in response to glucagon (10(-5) to 10(-10) M) was diminished in hepatocytes from hypothyroid rats, compared with those from euthyroid animals. PMID- 2883281 TI - The synergistic effects of concurrent administration to rats of EDTA and sodium salicylate on the rectal absorption of sodium cefoxitin and the effects of inhibitors. AB - Plasma levels of cefoxitin, as enhanced by rectal coadministration of sodium salicylate, were reduced by concurrent administration of less than 0.5 mg mL-1 N ethylmaleimide (NEM) or p-chloromercuriphenylsulphonic acid, sodium salt (p-CMP). Concentrations of these inhibitors above 1 mg mL-1 resulted in enhanced peak plasma values of cefoxitin. This did not occur after coadministration with either ethylenediaminetetraacetic acid (EDTA) or polyoxyethylene-23 lauryl ether (POE). Ouabain and 2,4-dinitrophenol (DNP) suppressed plasma cefoxitin levels in the presence of salicylate and the enhancing effects of EDTA and POE when EDTA and POE were administered at low doses. At higher concentrations of EDTA and POE, DNP had little effect, while ouabain had little effect on POE and only partially suppressed the effects of EDTA. Plasma concentrations of cefoxitin after coadministration with salicylate and POE together, or with EDTA and POE together, were about the same as expected from summing the plasma levels resulting from coadministration of each adjuvant individually at the same concentrations. However, combined administration of salicylate and EDTA with cefoxitin yielded plasma cefoxitin concentrations which were much higher than expected from the sum of their individual actions. PMID- 2883280 TI - Comparison of the mode of action of succinylcholine and succinylmonocholine on rat skeletal muscle after denervation. AB - The effects of equimolar concentrations (3.0 X 10(-5) M) of succinylcholine (SCh) and succinylmonocholine (SMC) were studied in-vitro at 20 degrees C in rat extensor digitorum longus muscle (EDL) 0-147 days after common peroneal nerve section. Analysis of simultaneous measurements of K+ efflux (mmolL-1 g-1) and contracture tension (mN) to SCh showed that there was a rapid increase in the mean values of both parameters up to 22-28 days after denervation (7.7 mmolL-1 g 1, 36 mN). At the end of the period studied, the contracture response declined to 4.0 mN whilst the capacity for K+ efflux remained relatively high (4.8 mmolL-1 g 1) in comparison with normal contralateral EDL muscle (n = 82) K+ efflux measurements (0.62 mmolL-1 g-1). A significant correlation (r = 0.86, P less than or equal to 0.001) was found between SCh-induced K+ efflux and contracture tension 1-56 days following nerve section which indicated that the development of the contracture response and K+ efflux were concomitant during the period specified. The ratios of maximum contracture tension/K+ efflux in response to SCh and SMC, 18-22 days after denervation were similar, 4.9 and 5.9, respectively. Results indicated that the mode of action of each agent was similar in denervated rat skeletal muscle, and that they were equally potent in their hyperkalaemic potential. Results of comparative measurements of membrane depolarization and contracture tension in response to SCh and SMC showed that both agents produced quantitatively similar responses at 7 and 14 days after denervation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883282 TI - An investigation of the mechanism involved in the cholinergic action of meptazinol. AB - In concentrations above 20 microM, (+/-)-meptazinol produced a contraction of the guinea-pig isolated ileum and this effect was antagonized by atropine (0.01 to 0.3 microM) in a manner which was not competitive. Cooling the preparation to 15 degrees C blocked the contractile action of meptazinol and of dimethylphenylpiperazinium (DMPP) but did not affect the action of carbachol. Twitch responses of the rat phrenic nerve-diaphragm preparation induced by indirect electrical stimulation in the presence of naloxone (20 nM) were potentiated by meptazinol (1 to 40 microM) which also reversed a partial blockade of the twitch induced by tubocurarine. Neither of these effects was seen in tissues which had been pretreated with the cholinesterase inhibitor BW284C51 (0.2 microM) though tetraethylammonium iodide (40 microM) was still able to enhance the responses to stimulation. In the presence of naloxone (20 nM) electrically induced responses of the rat isolated rectum were abolished by cinchocaine (10 microM), partially blocked by atropine (0.1 to 0.4 microM) and potentiated by meptazinol (1 to 30 microM). The latter action was not seen when meptazinol was administered in the presence of BW284C51. It is concluded that the cholinergic action of meptazinol in these tissues is due to an indirect effect, probably involving inhibition of cholinesterase and that no evidence was seen of any ability to increase the release of acetylcholine itself. PMID- 2883283 TI - The effects of pH, calcium and chloride ions on the binding of tolmetin to human serum albumin: circular dichroic, dialysis and fluorometric measurements. AB - The binding of the non-steroidal anti-inflammatory drug, tolmetin (1-methyl-5-p toluoylpyrrole-2-acetic acid) to human serum albumin (HSA) has been shown by circular dichroism, fluorescence and equilibrium dialysis to be dependent on the N-B conformational change of the albumin. The influence of calcium and chloride ions on the interaction was also investigated using the same techniques. Experiments suggested that calcium ions increased the binding constant of tolmetin to HSA whereas chloride ions decreased it. The displacement study showed that tolmetin caused a significant increase in the affinity of diazepam to HSA whereas it decreased the binding of warfarin to HSA. Tolmetin seems to cause an allosteric change in the diazepam binding site in spite of it sharing a primary site with warfarin. PMID- 2883284 TI - Comparison of changes in locomotor activity with striatal homovanillic acid and 3,4-dihydroxyphenylacetic acid concentrations following the bilateral intranigral injection of dopamine agonist drugs in rats. AB - Bilateral injection of apomorphine (2.5 micrograms) into the substantia nigra zona reticulata of rats reduced both locomotor activity and striatal HVA and DOPAC concentrations. Bilateral injection of dopamine (10 micrograms) did not affect locomotor activity whereas a higher dose of dopamine (50 micrograms) enhanced locomotor activity. Striatal HVA and DOPAC concentrations were unchanged following injection of dopamine. Bilateral injection of (+/-)-3PPP (0.1 or 2.5 micrograms) into the zona reticulata of the substantia nigra did not alter locomotor activity while a higher dose (10 micrograms) enhanced locomotion. Injection of (+/-)-3PPP (0.1-10 micrograms) into the zona reticulata was without effect on striatal HVA or DOPAC concentrations. The bilateral manipulation of nigral dopaminergic neurotransmission alters motor activity and nigrostriatal dopamine turnover in conscious rats. However, the changes in motor activity are not necessarily related to altered nigrostriatal activity, suggesting the involvement of dopamine receptors located at non-dopaminergic sites within the substantia nigra. PMID- 2883286 TI - The binding of the benzimidazole dye H8208 to DNA and to polyinosinic polycytidylic acid. AB - The benzimidazole dye H8208 (2-(4-aminophenyl)-5-(4-methylpiperazin-1-yl) benzimidazole) has been shown to intercalate into calf thymus DNA and into polyinosinic-polycytidylic acid (a model for A conformation DNA) by a variety of spectroscopic techniques. The binding affinity of the dye was found to be similar to both nucleic acids. PMID- 2883285 TI - Effects of the pyrones, maltol and ethyl maltol, on iron absorption from the rat small intestine. AB - The pyrones, 3-hydroxy-2-methyl-4-pyrone (maltol) and 3-hydroxy-2-ethyl-4-pyrone (ethyl maltol) chelate iron with a high affinity and selectivity. The resulting 1:3 (metal-ligand) complexes, being neutral, are able to partition readily across cell membranes and thus may facilitate iron transport across the intestinal wall. Absorption of radioactive iron (59Fe) in the presence of these pyrones was investigated in male rats 1, 2, 4 and 6 h after intraduodenal administration of a 7 micrograms dose and compared with that of 59Fe given as the sulphate, gluconate, fumarate or complexed to EDTA. Total body absorption and distribution were calculated from the 59Fe content of various tissue samples. With all the iron preparations used, blood levels of 59Fe were highest 1 h after injection whilst the 59Fe content at the major site of deposition, i.e. the bone marrow, increased up to 6 h. No 59Fe was found in the urine. Total body absorption of 59Fe was significantly higher from the pyrones than from the other four preparations. Over the dose range 0.7-700 micrograms, the proportion of 59Fe absorbed from both iron maltol and iron sulphate decreased with increasing dose. Enhanced 59Fe uptake from maltol was evident at 0.7-70 micrograms but not at 700 micrograms suggesting that use of these pyrones will not result in iron overload. Absorption of 59Fe given into the stomach was slower in onset but was sustained longer presumably via a steady delivery of iron to the duodenum from the gastric reservoir.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883288 TI - An investigation of sex-linked differences to the toxic and to the pharmacological actions of difenacoum: studies in mice and rats. AB - We have investigated the actions of the coumarin anticoagulant, difenacoum, in male and female rats and mice. In our first experiment difenacoum (0.5 mg kg-1) killed 50% of male mice within 9 days of its administration, whereas no female mice died during this study. In a second group of experiments, the anticoagulant effect of difenacoum in male and female rats was determined. Under resting conditions, the prothrombin complex activities (PCA) of male and female rats were not significantly different. Over the first 24 h after administration of difenacoum (0.4 mg kg-1 i.p.), there was a monoexponential fall in PCA in both sexes. However, 6, 12 and 24 h after difenacoum, the PCA in male rats was significantly (P less than 0.05) lower than in female rats. PCA began to recover over the subsequent 48 h in both sexes, during which time there was marked variability in recovery in female rats. The difference between the onset of action of difenacoum in male and female rats did not appear to be due to a greater rate of elimination of the drug in female rats, since the plasma concentrations of difenacoum 24 h after its administration were the same in both sexes. The concentration of vitamin K1 in rat liver was also investigated. Vitamin K1 levels were 35.1 +/- 18.6 ng (g liver)-1 (male), and 29.4 +/- 5.4 ng (g liver)-1 (females) in control rats, but 24 h after difenacoum, vitamin K1 levels were either very low, or undetectable in all rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883287 TI - Kinetics of hydrolysis of meclofenoxate hydrochloride in human plasma. AB - The kinetics of hydrolysis of meclofenoxate hydrochloride in human plasma have been compared with those of clofibrate. The hydrolysis rate in fractionated plasma was determined in the presence and absence of a plasma esterase inhibitor, tetraethyl pyrophosphate. The kinetic data indicated that clofibrate decomposed only by esterase-induced hydrolysis, which was inhibited by binding of clofibrate to plasma proteins. In contrast to clofibrate, meclofenoxate decomposed rapidly in human plasma via spontaneous hydrolysis as well as esterase-induced hydrolysis. The spontaneous hydrolysis appeared to be inhibited by some components present in the esterase fraction isolated from plasma, while no significant inhibition of the hydrolysis by protein binding was observed. PMID- 2883289 TI - The effect of meptazinol on the guinea-pig sphincter of Oddi in-vitro. AB - Meptazinol causes a dose-dependent contraction of the guinea-pig sphincter of Oddi in-vitro. This was antagonized by atropine in concentrations which blocked the contractile response to acetylcholine but not that to KCl. Naloxone was unable to block the response of the tissue to meptazinol, and other opioid drugs had inconsistent effects. Although meptazinol has significant anticholinesterase activity on this preparation, comparison with neostigmine suggests that this is irrelevant to its contractile action. PMID- 2883290 TI - Intravenous kinetics and metabolism of [15,16-3H]naltrexonium methiodide in the rat. AB - After a 4 mg kg-1 bolus intravenous dose of [15,16-3H]naltrexonium methiodide to the rat, brain to plasma concentration ratios of the compound were 0.031 to 0.228 between 0.25 to 6 h after injection and the t 1/2 beta in plasma and brain were 2.92 and 7.61 h, respectively. Ethyl acetate-extracted radioactivity due to metabolites in plasma decayed with t 1/2 beta 1.83 h and the ratios of plasma concentration of metabolites to quaternary compound between 0.25 and 6 h were 0.014-0.026. Only unconjugated 7,8-dihydro-14-hydroxynormorphine, naltrexone and traces of 7,8-dihydro-14-hydroxynormorphinone were the metabolites in plasma. Naltrexone (but not normetabolites) was present only in traces in brain up to 0.5 h after injection and not at later times. PMID- 2883291 TI - Comparison of the effects of Fe2+ and Cu2+ on prostaglandin synthesis in rabbit kidney medulla slices. AB - The effects of Fe2+ and Cu2+ on the generation of medullary prostaglandins E2 and F2 alpha have been compared. Fe2+ markedly promoted the lipid peroxidation of rabbit kidney medulla slices. The lipid peroxidation induced by Fe2+ inhibited both prostaglandin E2 and prostaglandin F2 alpha formation to a similar extent. While Cu2+ produced only a small increase in lipid peroxidation, it had a powerful inhibitory effect on prostaglandin E2 formation. Simultaneously, prostaglandin F2 alpha production was increased. In the presence of Cu2+ the net increased amount of prostaglandin F2 alpha was much smaller than the net decreased amount of prostaglandin E2 (15-20%). These results suggest that Cu2+ has the potential to modulate prostaglandins E2 and F2 alpha synthesis by affecting endoperoxide E2 isomerase or endoperoxide reductase independent of its peroxidative action. PMID- 2883292 TI - The relationship of the pharmacokinetics of chloroquine to dose in the rabbit. AB - Four albino rabbits were treated with 4 different doses of chloroquine phosphate (30-50 mg kg-1) given intragastrically and 10 others were given the hydrochloride (2.5-12.5 mg kg-1 i.v.). The i.v. doses were given as bolus into the median ear vein over 5-8 min. Samples (3-5 mL) of whole blood were subsequently collected at intervals for up to 6 weeks and analysed by HPLC. From the results, log concentration-time curves were drawn and the i.v. data fitted by computer to 3 compartment (8 rabbits) or 2-compartment curves (2 rabbits). The area under the curve (AUC) and half-lives were calculated for the different doses. A plot of AUC versus dose yielded a straight line but the half-lives showed wide inter individual variation from the same doses. PMID- 2883293 TI - Detrimental effect of propylene glycol on natural killer cell and neutrophil function. AB - Propylene glycol (PG) in a concentration of 0.5-1.0% inhibits natural cytotoxicity and neutrophil chemiluminescence. This is the first reported effect of PG on defence mechanisms in man. PG is frequently used as a vehicle in high concentrations by the pharmaceutical industry and it would be wise to consider its potential immunosuppressive effects in the evaluation of drug formulations. PMID- 2883294 TI - Specific binding of [3H]methylscopolamine to glass fibre filters. PMID- 2883295 TI - Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain. AB - (+/-)-3,4-Methylenedioxymethylamphetamine (MDMA) was administered s.c. to rats (10, 20 or 40 mg/kg b. wt.) and guinea pigs (20 mg/kg) twice a day for 4 days, 2 weeks before decapitation. Norepinephrine, dopamine and serotonin (5-HT) levels were assayed in the hippocampus, hypothalamus, striatum and neocortex. In rats, MDMA produced dose-dependent reductions in 5-HT in all brain regions examined. The highest dose also reduced norepinephrine and/or dopamine in some regions. The 20-mg/kg dose of MDMA depleted 5-HT in all regions of the guinea pig brain assayed. In both species, repeated administration of 20 mg/kg of MDMA reduced the Vmax but not the Km of 5-HT uptake 2 weeks after administration. A single 40 mg/kg injection of MDMA depleted 5-HT 2 and 8 weeks after administration to rats in all regions of the brain examined except the hypothalamus. Administration of 80 mg/kg of MDMA twice a day for 2 days to rats depleted striatal 5-HT and dopamine. Brain sections from rats injected with MDMA according to this dosage regimen were stained by the Fink-Heimer method. Degenerating axon terminals and cell bodies were observed in the striatum and somatosensory cortex, respectively. These findings suggest that MDMA is toxic to serotonergic and, to a lesser extent, catecholaminergic neurons. Some neurons that do not contain these transmitters (neocortical neurons) are also affected. PMID- 2883296 TI - Effects of adrenergic receptor antagonists on cardiac morphological and functional alterations in rats harboring pheochromocytoma. AB - New England Deaconness Hospital rats harboring a transplantable pheochromocytoma exhibit plasma norepinephrine concentrations 20-fold higher than controls. A cardiomyopathy (CM) characterized by multifocal areas of interstitial and replacement fibrosis, mixed inflammatory infiltrates and contraction band necrosis is evident 35 to 45 days after tumor implantation. Using a morphological scoring system of 0 (no cardiac damage) to 3 (involvement of almost the complete ventricular cross-section sampled), a CM score of 1.8 +/- 0.1 was found in rats harboring pheochromocytoma, a significant increase over that in age- and sex matched controls (0.4 +/- 0.1, P less than .001). The pheochromocytoma rats also had hypertension (systolic blood pressure = 182 +/- 4 vs. 131 +/- 2 mm Hg in controls, P less than .001). In an effort to prevent the CM, rats harboring pheochromocytoma were treated with either the beta receptor antagonist timolol, the alpha receptor antagonists phentolamine or phenoxybenzamine or the nonspecific vasodilator hydralazine. Hydralazine normalized systolic blood pressure (135 +/- 6 mm Hg), whereas timolol (144 +/- 5 mm Hg), phenoxybenzamine (166 +/- 5 mm Hg) or phentolamine (154 +/- 10 mm Hg) only moderately decreased blood pressure in rats harboring pheochromocytoma. Hydralazine had no effect on CM score (1.8 +/- 0.1). Timolol markedly attenuated the CM score (0.6 +/- 0.1), whereas the alpha adrenergic antagonists were not as effective (phenoxybenzamine CM score = 1.3 +/- 0.2; phentolamine CM score = 1.7 +/- 0.2). Furthermore, timolol prevented desensitization of beta adrenergic receptor-mediated contraction in the hearts of rats harboring pheochromocytoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883297 TI - Gastric antisecretory and antiulcer effects of WHR1582A, a compound exerting alpha-2 adrenoceptor agonist activity. AB - The gastric antisecretory and antiulcer effects of a novel compound, [1-(2, dimethylphenyl)-3-isobutoxyamidinourea]hydrochloride (WHR1582A), are described. WHR1582A was active in preclinical ulcer models induced by 18-hr pylorus ligation, aspirin, indomethacin, reserpine, stress or cysteamine. WHR1582A inhibited acid secretion in the pylorus-ligated rat and in the anesthetized, lumen-perfused rat. The antisecretory effects of WHR1582A were antagonized by yohimbine, RX781094A and phentolamine. Propranolol, prazosin, corynanthine, methysergide, sulpiride and pimozide were unable to block its activity. WHR1582A blocked acid secretion stimulated by 2-deoxy-D-glucose but was inactive against the direct parietal cell stimulants carbachol and dimaprit. WHR1582A also inhibited electrically stimulated contractions that were mediated via the vagus in the isolated rat stomach preparation. The antisecretory activity of WHR1582A was not due to a reduction in gastric mucosal blood flow. These results demonstrate that WHR1582A is an effective antiulcer-antisecretory agent that exerts its gastric effects through the activation of alpha-2 adrenoceptors located presynapitcally on the vagus. PMID- 2883298 TI - Biochemical characterization of the triazoloquinazoline, CGS 15943, a novel, non xanthine adenosine antagonist. AB - CGS 15943A, a triazoloquinazoline, is a potent and selective adenosine receptor antagonist as assessed by its effects on radioligand binding and adenosine stimulated adenylate cyclase activity in guinea pig synaptoneurosomes. At the adenosine A-1 receptor labeled with [3H]cyclohexyladenosine, CGS 15943A had an IC50 value of 20 nM. At the striatal A-2 receptor labeled with [3H]5'-N ethylcarboxamidoadenosine in the presence of a low concentration of cyclopentyladenosine to block A-1 receptors labeled by this nonselective adenosine agonist, CGS 15943A had an IC50 value of 3 nM, indicating that the compound had some degree of selectivity for the A-2 receptor. Analysis of the effect of the compound on the saturation isotherms for each of the receptors indicated that it was a competitive antagonist at the brain A-1 receptor but that it was noncompetitive at the striatal A-2 receptor. CGS 15943A was a potent adenosine antagonist in the adenosine-stimulated adenylate cyclase system in guinea pig synaptoneurosomes, where the compound was found to have an IC50 value of 30 to 70 nM against the increase in cyclic AMP evoked by 5 microM adenosine. CGS 15943A had no effect on the binding of [3H]nitrobenzylthioinosine, a ligand thought to bind to adenosine uptake sites, and, at a concentration of 10 microM, had no effect on beef heart type III phosphodiesterase activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883299 TI - Alpha-1 adrenergic coupling events induced by full and partial agonists in rabbit aorta. AB - Differences in the ability of full vs. partial agonists to initiate alpha-1 adrenergic receptor-mediated coupling events were studied in isolated segments of rabbit aorta. Mono- and dimethoxysubstituted tolazolines produced contractile responses which, at their maximum, were 27 to 100% of the response produced by the full agonist phenylephrine. In addition to differences in maximum response, contraction kinetics varied between full and partial agonists. Responses to partial agonists displayed a slower approach to peak tension and loss of the rapid phase of tension development which is associated with release of intracellular Ca++. Among the tolazoline series 3,5 dimethoxy-, 3 methoxy-, and 2 methoxy derivatives were compared further with phenylephrine for their ability to cause phosphatidylinositol cycle turnover, intracellular Ca++ release and Ca++ influx. For each of these coupling events, a rank of phenylephrine greater than or equal to 3, 5 greater than 3 greater than 2 was observed. However, a higher percentage of Ca++ influx vs. Ca++ release was observed for the partial agonists, suggesting that their contractile responses may be more dependent upon extracellular Ca++ than intracellular Ca++. Our results indicate that partial agonists initiate the same coupling events as full agonists; however, the relative proportion of Ca++ release and influx may be different for partial agonists because of the reduced rate of second messenger production. PMID- 2883300 TI - In vivo assessment of rat renal alpha adrenoceptors. AB - Despite a preponderance of alpha-2 adrenoceptors in homogenates of rat renal cortex, alpha-2 adrenoceptor agonists do not vasoconstrict the isolated buffer perfused rat kidney. Both alpha-1 and alpha-2 adrenoceptor agonists can constrict the kidneys of dogs, cats and rabbits in vivo. Because alpha-2 adrenoceptor mediated vasoconstriction is often difficult to demonstrate in vitro, and both subtypes of alpha agonists cause large increases in peripheral resistance in pithed rats, we tested the hypothesis that both alpha-1 and alpha-2 agonists would also constrict the rat kidney in vivo. Cannulation of the suprarenal artery and utilization of a high pressure liquid chromatography valve enabled random and reproducible intrarenal arterial bolus injections of agonists, and renal blood flow was monitored using Doppler flowmetry. Cirazoline, phenylephrine and norepinephrine bitartrate caused large renal vasopressor responses with minimal systemic effects. Although administered in a dosage range 100 to 1000 times that of alpha-1 agonists, the alpha-2 agonists (B-HT 920, UK 14,304 and guanabenz) produced only minimal renal vasoconstriction before systemic pressor effects. The low potency and efficacy of alpha-2 agonists could not be attributed to concomitant vasodilatory effects of these agents. Rat renal resistance vessels were less responsive to alpha-2 agonists than other species that have been examined. These studies are consistent with conclusions from in vitro examinations that only alpha-1 adrenoceptors mediate changes in renal vascular resistance and also autoradiographic studies reporting the localization of alpha 2 binding sites to rat renal tubules. PMID- 2883301 TI - Pentobarbital-like discriminative stimulus properties of halothane, 1,1,1 trichloroethane, isoamyl nitrite, flurothyl and oxazepam in mice. AB - Volatile inhalants represent a diverse group of chemicals which pose a public health problem because of their abuse potential and neurobehavioral toxicity. Although relatively little is known about their pharmacology, they share certain pharmacological properties with classic central nervous system depressants. Drug discrimination procedures were used to compare the effects produced by pentobarbital (PB), oxazepam and several inhalants. Mice were trained to discriminate PB from saline injections in a two-lever operant task. Stimulus generalization was examined after 20-min inhalation exposures to halothane (500 8000 ppm), 1,1,1-trichloroethane (500-12000 ppm), isoamyl nitrite (150-1050 ppm), flurothyl (562-1300 ppm) and injections of oxazepam (0.1-20 mg/kg). Halothane, 1,1,1-trichloroethane and oxazepam produced discriminative stimulus effects similar to those produced by PB. Isoamyl nitrite and flurothyl, while decreasing rates of responding, were not consistently generalized from PB. Differences are apparent in the PB-like discriminative effects of inhalants. Toluene, as shown in a previous study, as well as halothane and 1,1,1-trichloroethane have PB-like discriminative effects which are also shared by oxazepam and may be another common effect of central nervous system depressants. Other chemicals, like isoamyl nitrite and flurothyl, are representative of qualitatively different classes of behaviorally active inhalants. PMID- 2883303 TI - AF-DX 116, a cardioselective muscarinic antagonist. AB - The M2 subtype of the muscarinic receptor was investigated using the antagonist AF-DX 116. In "in vitro" and "in vivo" experiments, AF-DX 116 behaved as a competitive antagonist and exhibited a selectivity for cardiac muscarinic mediated functions. It antagonized negative chronotropic and inotropic effects exerted by muscarinic receptor activation in the guinea pig atria with an affinity (pA2) 10-fold greater than that estimated in intestinal and tracheal smooth muscle preparations. It also reversed the negative chronotropic effect induced by peripheral vagal stimulation, intrasinus node injection of bethanechol and central vagal activation by clonidine. In all these in vivo functions, AF-DX 116 was approximately 10 times less potent than atropine, while being several hundred-fold less potent in antagonizing acetylcholine-mediated bronchoconstriction and gastric emptying. These results are consistent with the hypothesis that the cardiac muscarinic receptors constitute a subclass of the M2 subtype. PMID- 2883302 TI - Identification of pre- and postsynaptic bradykinin receptor sites in the vas deferens: evidence for different structural prerequisites. AB - The effect of bradykinin on the neuroeffector junction of the isolated rat vas deferens was studied in tissues stimulated transmurally at a frequency of 0.15 Hz. Bradykinin caused two distinct and independent actions: it potentiated the magnitude of the muscular response to the electrically driven twitches and, in addition, contracted the smooth muscle generating an increased muscular tone. The former action is referred to as the neurogenic or presynaptic effect, whereas the latter effect is called the musculotropic or postjunctional action. The neurogenic effect was abolished by tetrodotoxin or tissue denervation either by cold storage or chemical sympathectomy after 6-hydroxydopamine administration. However, these procedures did not significantly modify the musculotropic potency of bradykinin. Both actions of the peptide are receptor-mediated, as minor structural modifications in the amino acid sequence caused significant changes in biological potency. In addition, the peptide analog, [Thi5,8-D-Phe7]-bradykinin, behaved as an agonist at the presynaptic site but as an antagonist at the muscular site. The most potent peptide analog to produce the neurogenic effect was Met-Lys-bradykinin followed by Lys-bradykinin and [Tyr8]-bradykinin. In contrast, the potency of these peptide analogs acting at the postsynaptic site was about the same. des Arg9 bradykinin and des Arg9-[Leu8]-bradykinin were inactive at the pre- and postjunctional site. The neurogenic action of bradykinin was not mimicked by angiotensin II, neurotensin, substance P or vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883304 TI - In vivo electrochemical demonstration of the presynaptic actions of phencyclidine in rat caudate nucleus. AB - In vivo electrochemical recordings, coupled with local application of drugs from micropipettes, were used to determine the presynaptic effects of phencyclidine (PCP) on dopamine-containing nerve terminals in the intact rat striatum. Local application of PCP did not elicit an observable increase in extracellular levels of the monoamine neurotransmitters. However, pretreatment with PCP significantly potentiated the potassium-evoked release of monoamines. Nomifensine, a potent catecholamine reuptake blocker, produced effects that were analogous with PCP. Local pretreatment with PCP was also found to potentiate the electrochemical signal detected after pressure ejection of dopamine directly into the caudate nucleus. Finally, electrophysiological studies showed that locally applied PCP and nomifensine solutions had similar potencies in depressing the spontaneous firing of striatal neurons. Taken together, these data suggest that the major presynaptic action of PCP in the rat caudate nucleus is inhibition of the reuptake, and not alteration of release, of the monoamine neurotransmitters. PMID- 2883305 TI - Interactions of beta adrenergic antagonists with isolated rat alveolar type II pneumocytes. I. Analysis, characterization and regulation of specific beta adrenergic receptors. AB - Binding of beta adrenergic receptors (BAR) in membranes of freshly isolated type II pulmonary epithelial cells to the radioligand [125I]iodocyanopindolol was saturable, steresospecific and of high affinity. Optimal conditions for the assay of BAR on type II pneumocyte membranes are presented. Type II pneumocyte BAR are primarily of the beta-2 subtype, as indicated by inhibition of subtype-specific antagonists, ICI 118,551 and betaxolol. Maximum binding and Kd were measured (Kd, 4-20 pM; maximum binding, 30-50 fmol/mg of protein) and used to identify factors which alter BAR. The number of BAR on type II pneumocytes doubled after 42-hr culture in the presence of dexamethasone. Ligand-receptor interactions were of similar affinity to those in membrane particulates from whole lung, but maximum binding was reduced 3- to 4-fold. Less than 5% of total pulmonary BAR can be accounted for by those expressed on freshly isolated type II pneumocyte membranes. Other cell types thus probably account for the majority of specific beta adrenergic binding sites in the lung as a whole. PMID- 2883306 TI - Interactions of beta adrenergic antagonists with isolated rat alveolar type II pneumocytes. II. Receptor-independent accumulation of beta adrenergic antagonists and other cationic amphiphilic drugs in lamellar bodies. AB - Accumulation of basic drugs by pulmonary tissue is well known. The cationic amphiphilic nature of many of these compounds suggests that they may be sequestered within an acidic and/or phospholipid-rich compartment. We described previously receptor-independent, concentrative, temperature- and pH-dependent sequestration of the beta adrenergic antagonists [125I]iodocyanopindolol and [125I]iodopindolol by intact rat type II pneumocytes in primary culture. The present study reveals that type II pneumocytes sequester [125I]iodocyanopindolol to an extent greater than other cell types (type II cells greater than polymorphonuclear leukocytes greater than S49) within 80-min incubations. Localization of fluorescence into large granular structures was observed after incubation of type II cells with 9-aminoacridine-propranolol (9-AAP). The distribution of fluorescence coincides with surfactant-containing lamellar bodies (LB) visualized with tannic acid/osmium staining. The large granule localization of 9-AAP fluorescence decreases with time in primary culture in parallel with changes in cell morphology and decreased numbers of LB. Comparison of patterns of fluorescence after incubation with 9-AAP, acridine orange and 9-aminoacridine (all 1 microM) indicates that localization is not a property of the acridine moiety, but requires the propranolol side-chain. Association of 9-AAP fluorescence with LB is inhibited completely by chlorpromazine (10 microM); the same concentration of propranolol or chlorquine produces less extensive, but detectable, inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883307 TI - Antifibrillatory efficacy of concomitant beta adrenergic receptor blockade with dilevalol, the R,R-isomer of labetalol, and muscarinic receptor blockade with methylscopolamine. AB - The antiarrhythmic and antifibrillatory actions of dilevalol, the R,R-isomer of labetalol, were evaluated in conscious dogs 4 to 6 days after anterior myocardial infarction. The administration of dilevalol in a lower dose of 0.3 mg/kg i.v. q 8 hr or a higher dose of 3.0 mg/kg i.v. q 8 hr over a period of 24 hr failed to alter electrophysiologic parameters or significantly suppress the induction of ventricular tachycardia by programmed ventricular stimulation (incidence of ventricular tachycardia suppression: 4 of 25 [16%] dilevalol vs. 1 of 14 [7%] vehicle). Pretreatment with dilevalol failed to reduce arrhythmic death in response to the subsequent development of ischemia at a site distant to the area of previous infarction (mortality: 8 of 10 [80%] dilevalol vs. 14 of 14 [100%] vehicle), but did alter the nature of the lethal ischemic arrhythmia from ventricular fibrillation (incidence of ventricular fibrillation: 14 of 14 [100%] vehicle vs. 2 of 8 [25%] dilevalol, P less than .05) to bradyarrhythmia with eventual sinoatrial arrest (6 of 8 [75%] dilevalol). The administration of methylscopolamine, 0.01 mg/kg both i.v. and i.m., to postinfarction animals pretreated with dilevalol, 3.0 mg/kg i.v. q 8 hr for 24 hr, reduced significantly mortality in response to subsequent posterolateral ischemia (mortality: 4 of 10 [40%] dilevalol plus methylscopolamine vs. 14 of 14 [100%] vehicle, P less than .05). However, methylscopolamine alone failed to suppress the development of ischemic ventricular fibrillation in 5 of 6 (83%) postinfarction dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883308 TI - Primary culture of striatal neurons: a model of choice for pharmacological and biochemical studies of neurotransmitter receptors. AB - Striatal neurons were cultured from fetal mouse brain and maintained in serum free medium for 14-21 days in vitro (DIV). A double coating of culture dishes with polyornithine and fetal calf serum was needed in order to obtain synaptic differentiation. Synaptic vesicles were present in axon terminals as well as in varicosities along extended axons. The presence of differentiated synapses was confirmed by the immunostaining of the preparation with synapsin I antibody. After 13 days in vitro synapsin I was present in axonal varicosities and particularly concentrated at contact points between axonal terminals and postsynaptic sites on adjacent axons or perikarya. On a surface of 429 mm2 on which 2211 cells were observed under phase contrast microscopy only 7% were stained with an antibody against GFAP (glial fibrillary acidic protein). One or two days after the formation of differentiated synapses (11 DIV), a Ca2+ dependent liberation of GABA was observed. These cultures are an excellent model for studying the coupling of some neurotransmitter receptors with an adenylate cyclase. In particular using this preparation we were able to demonstrate that dopamine (D2) and serotonin-(5-HT1) receptors are negatively coupled with an adenylate cyclase. These cultures are also an excellent model to study the coupling of some neurotransmitter receptors with inositol phosphate producing enzymes. We demonstrated for the first time that the quisqualate subtype of glutamate receptors is able to increase inositol phosphate production in striatal neurons. PMID- 2883309 TI - Postsynaptic control of hippocampal long-term potentiation. AB - Long-term potentiation (LTP) in the hippocampus has the property of cooperativity, i.e. greater potentiation is produced if a larger number of afferent fibres is tetanized. The possible involvement of postsynaptic mechanisms in this process was investigated in the CA1 area of the hippocampal slice preparation. Following blockade of postsynaptic inhibition by GABA antagonists, e.g. picrotoxin, the induction of LTP was greatly facilitated. In picrotoxin treated slices, LTP was induced in a pathway stimulated by single volleys, if these occurred in conjunction with brief tetanic activation of other afferents. This interaction operated over a short period of time (less than 50 ms) and was also present if the inputs were separated in space (cooperativity between inputs to basal and apical dendrites). LTP could be induced by pairing single volley synaptic activation and intracellularly injected depolarizing current pulses, the timing requirements being similar to those observed in the extracellular "conjunction studies". Previous studies have suggested that glutamate receptor channels of the N-methyl-D-aspartate (NMDA) type are somehow involved in LTP induction. Evidence presented here shows that activation leading to LTP evokes a potential which is sensitive to the NMDA receptor blocker 2-amino-5 phosphonovalerate (APV), indicating passage of current through NMDA receptor channels. The results suggest that hippocampal LTP depends on simultaneous presynaptic transmitter release and postsynaptic depolarization in a manner analogous to the model proposed by HEBB (1949) for associative learning. Furthermore, it is proposed that the required pre- and postsynaptic interaction is handled by the NMDA receptor channel complex, which is known to have the required voltage and transmitter sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883310 TI - Can presynaptic depolarization release transmitter without calcium influx? AB - Recent experimental evidence suggesting that presynaptic depolarization can evoke transmitter release without calcium influx has been re-examined. The presynaptic terminal of the squid giant synapse can be depolarized by variable amounts while recording presynaptic calcium current under voltage clamp and postsynaptic responses. Small depolarizations open few calcium channels with large single channel currents. Large depolarizations approaching the calcium equilibrium potential open many channels with small single channel currents. When responses to small and large depolarizations eliciting similar total macroscopic calcium currents are compared, the large pulses evoke more transmitter release. This apparent voltage-dependence of transmitter release may be explained by the greater overlap of calcium concentration domains surrounding single open calcium channels when many closely apposed channels open at large depolarizations. This channel domain overlap leads to higher calcium concentrations at transmitter release sites and more release for large depolarizations than for small depolarizations which open few widely dispersed channels. At neuromuscular junctions, a subthreshold depolarizing pulse to motor nerve terminals may release over a thousand times as much transmitter if it follows a brief train of presynaptic action potentials than if it occurs in isolation. This huge synaptic facilitation has been taken as indicative of a direct effect of voltage which is manifest only when prior activity raises presynaptic resting calcium levels. This large facilitation is actually due to a post-tetanic supernormal excitability in motor nerve terminals, causing the previously subthreshold test pulse to become suprathreshold and elicit a presynaptic action potential. When motor nerve terminals are depolarized by two pulses, as the first pulse increases above a certain level it evokes more transmitter release but less facilitation of the response to the second pulse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883311 TI - Transmitter release from the cytoplasm is of physiological importance but not subject to presynaptic modulation. AB - Ca2+-dependent release of [3H] noradrenaline ([3H] NA) evoked by electrical stimulation of the isolated mouse vas deferens was subject to negative feedback modulation by idazoxan an alpha 2-adrenoceptor blocking agent. Both the resting release and that evoked by 1-phenylephrine proved to be Ca0-independent and unaffected by idazoxan. Ouabain-evoked release of [3H] acetylcholine from the myenteric plexus of ileal longitudinal muscle strips in the presence of eserine was not affected by atropine, but that evoked by electrical stimulation was enhanced. Since the release of NA or ACh by 1-phenylephrine and ouabain respectively is mainly of cytoplasmic origin, it is concluded that the release of transmitter from the cytoplasm is not subject to negative feedback modulation. PMID- 2883312 TI - Calcium is essential but insufficient for neurotransmitter release: the calcium voltage hypothesis. AB - A new Ca-voltage hypothesis for neurotransmitter release is proposed. Accordingly, membrane depolarization has two roles. To increase membrane conductance to calcium and to activate a molecule S from an inactive form T. Only the active form S binds calcium ions to start the chain of events leading to release. Four lines of experiments are described to support this hypothesis. Disassociation between Ca2+ entry and transmitter release. Loading of the terminal with Ca2+ and obtaining release with little additional entry of Ca2+. Measurements of kinetics of release. Modulation of release by changes in membrane potential. Recent criticism as to the validity of the experimental techniques used in the first two lines of experiments is analyzed and rejected. PMID- 2883314 TI - Tensile strength of an alternative soldered connector. PMID- 2883313 TI - The voltage-dependence of transmitter release. AB - In this paper we summarize voltage clamp experiments characterizing transmission at the squid giant synapse. The overall goal of these experiments was to determine a synaptic transfer curve relating presynaptic Ca currents (ICa) to resultant postsynaptic responses. Here we focus on interpreting the phenomenon of transfer curve "hysteresis", which has been proposed to result from an intrinsic voltage-dependence of the transmitter release process. One potential problem in analyzing transfer curves comes from contamination of presynaptic Ca currents by outward currents. Linear leakage currents can be measured and taken into account, but after such corrections ICa measurements at positive potentials are still distorted by outward currents. The presence of residual outward currents at positive potentials results in a voltage-dependent bias in ICa measurement and probably contributes to transfer curve hysteresis. A pharmacological procedure which subtracts currents other than those flowing through Ca channels can be used to circumvent this bias in ICa measurement. Gradients in membrane potential along a nominally voltage clamped presynaptic terminal can allow inappropriate release of transmitter from poorly clamped regions of the terminal. Release from such regions may also contribute to transfer-curve hysteresis when standard voltage clamp methods are employed. A method of localized Ca application which restricts transmitter release to well-clamped presynaptic regions can be used to avoid this problem. Transfer curves measured using refined procedures for ICa measurement and suppression of voltage gradient effects on release exhibit little hysteresis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883315 TI - Strength properties of soldered joints for a gold-palladium alloy and a palladium alloy. AB - Strength of a soldered palladium alloy, PGC (Engelhard Corp.), and a soldered medium gold alloy, PGX (Engelhard Corp.), was examined. The results obtained were as follows: Highest strength was observed with postsoldered specimens of PGC alloy. Microstructural examination of postsoldered specimens revealed nearly pore free solder joints with PGC and PGX alloys, and fracture appeared at the solder alloy interface with PGC and PGX alloys. Microstructural examination of presoldered and presoldered/thermocycled specimens revealed that presoldered specimens of PGC and PGX alloys exhibited intrasolder fracture; PGX solder joints had considerably less porosity, which may explain the equivalent bond strengths of all the soldered specimens and the yield point of the controls; PGC solder joints exhibited large quantities of pores, which may explain the lower strength; pores observed in PGC alloy may be the result of the high fusing temperature of the solder; and these results indicate a need to develop a new presolder for PGC. The best result was obtained with postsoldered specimens of the PGC alloy. However, for PGX alloy, either postsolder or presolder techniques can be used. PMID- 2883316 TI - Improved fixed partial denture soldering. PMID- 2883317 TI - Flavones. 1. Synthesis and antihypertensive activity of (3 phenylflavonoxy)propanolamines without beta-adrenoceptor antagonism. AB - The synthesis of a series of (3-phenylflavonoxy)propanolamines is described. These compounds were evaluated for potential antihypertensive activity in spontaneously hypertensive rats, as well as for in vivo and in vitro evidence of beta-adrenoceptor antagonism. Some of the compounds of this series exhibited effective antihypertensive properties but did not antagonize beta-adrenergic receptors. These active compounds represent a unique series of effective antihypertensive agents that, despite possessing structural characteristics typical of beta-blockers, does not have beta-adrenergic receptor blocking activity. PMID- 2883318 TI - Synthesis and neuroleptic activity of a series of 1-[1-(benzo-1,4-dioxan-2 ylmethyl)-4-piperidinyl]benzim idazolone derivatives. AB - A series of 1-[1-(benzo-1,4-dioxan-2-ylmethyl)-4-piperidinyl]benzimid azolones with various substituents in both aromatic rings have been synthesized and tested for neuroleptic activity (antiapomorphine effects and [3H]spiroperidol binding) as well as extrapyramidal effects (cataleptogenic effect). A strong dependence of activity on the 5-substituent in the benzimidazolone moiety could be demonstrated. Some compounds show a large split between the desired antiapomorphine and the undesired extrapyramidal effect. From these, 1-[1-(benzo 1,4-dioxan-2-ylmethyl)-4-piperidinyl]-5-chlor obenzimidazol-2-one hydrochloride (HR 723), 12, has been selected for further preclinical and toxicological profiling. PMID- 2883319 TI - Research strategies in human behaviour genetics. AB - Genetic variation influencing normal and abnormal human behaviour has been studied since Francis Galton's work in the second half of the 19th century. However, most of these studies have consisted of biometric analysis of complex phenotypes; the genotype has been treated as a 'black box'. The concepts and analytical tools of modern genetics have rarely been used. In this lecture, some examples are given of approaches combining tools from genetics, cytogenetics, and various fields of neurobiology which might help in the analysis of genetic mechanisms leading, in interaction with the environment, to individual differences in behaviour, mental performance, and susceptibility to mental diseases. PMID- 2883321 TI - Residents' underdocumentation in elderly patients' records of prescriptions for benzodiazepine. PMID- 2883320 TI - Exclusion of the alpha 2(I) and alpha 1(III) collagen genes as the mutant loci in a Marfan syndrome family. AB - The inheritance of restriction fragment length polymorphisms for two fibrillar collagen genes (COL1A2 and COL3A1) has been studied in a large Marfan syndrome kindred. We are able to show discordant segregation between the Marfan syndrome and each of the two collagen gene markers. PMID- 2883322 TI - Somatostatin effects in isolated human atrial fibres. AB - Effects of hypothalamic hormone somatostatin on the action potential and contractile force of 54 human atrial preparations obtained at cardiac surgery were studied with standard microelectrode techniques. In the atrial fibres responding to electrical stimuli with fast response action potentials in 4 mM [K]0 Tyrode solution (maximum rate of phase 0 depolarization greater than 50 V/s), somatostatin (10(-7) to 10(-6) M) reduced slightly the duration of action potential and decreased twitch force dose-dependently. In spontaneously active atrial fibres, somatostatin (10(-7) to 10(-6) M) abolished the action potentials in the preparations with low maximal diastolic potential (MDP, -48 +/- 2.8 mV), but induced only mild suppressive effect in the preparations with high MDP (-70 +/- 2.4 mV). When the fibres were depolarized in 27 mM [K]0 Tyrode solution, somatostatin decreased the maximum rate of depolarization and amplitude of the slow response action potentials induced by electrical stimuli. The delayed afterdepolarizations or triggered action potentials induced by high-frequency electrical drive in the presence of epinephrine were also suppressed by somatostatin. The above findings suggest that somatostatin may suppress the abnormal automaticity and the triggered activity in human atrial fibres through a reduction of cellular calcium. PMID- 2883323 TI - Significance of release of adenosine triphosphate and adenosine induced by hypoxia or adrenaline in perfused rat heart. AB - The status of ATP as a possible coronary vasodilator remains poorly understood. The onset of hypoxia induced a rapid and transient increase of the ATP concentration in the coronary effluent of the isolated perfused rat heart from 0.8 +/- 0.2 nM to the average peak value of 1.3 +/- 0.2 nM (P less than 0.01) at 2 +/- 0.5 min; at the same time the coronary flow increased 2-fold so that the rate of ATP release increased from 10.2 +/- 2.9 to 21.4 +/- 4.2 pmol/g/min (P less than 0.005). Hypoxia also produced a peak rate release of adenosine of 93 +/ 5 nM/g/min occurring only after the peak increase of coronary flow and also after the peak release of ATP; at peak coronary flow, however, the adenosine concentration was sufficient for vasodilation (0.31 +/- 0.19 microM). Peak release of ATP and of adenosine preceded that of lactate dehydrogenase. 10(-6) M adrenaline induced a rapid increase of coronary flow and release of ATP, the concentration of which rose from 0.9 +/- 0.3 nM to an average peak of 1.7 +/- 0.2 nM (P less than 0.01) at 2 +/- 0.3 min. The rate of increase of ATP in the coronary effluent paralleled the rate of early rise of coronary flow, yet adenosine had also risen to vasodilatory values (0.28 +/- 0.5 microM). The absolute changes in the measured concentrations of ATP in the coronary effluent were more variable and 1000 X less in concentration than those of adenosine. Hence coronary dilation could be explained by adenosine without involving ATP, although an additional vasodilatory role for ATP could not be excluded, especially in the early phases of vasodilation. In one condition, hypoxic K arrested hearts, the increase in coronary flow could not be linked to release of either adenosine or ATP. The changes in concentrations of potential vasodilators measured in the coronary effluent do not necessarily reflect changes in the interstitial fluid. PMID- 2883324 TI - Cellular localization of tyrosine hydroxylase mRNA and its regulation in the rat adrenal medulla and brain by in situ hybridization with an oligodeoxyribonucleotide probe. AB - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of catecholamines in neural tissues and adrenal medulla. To study the expression of the TH gene and its regulation in adult and developing neural tissues, we have synthesized an oligodeoxyribonucleotide probe (oligomer) that is specific for TH mRNA. Using Northern blot hybridization of polyadenylated RNAs from adrenal gland, brain stem, liver, and cerebral cortex with the 32P-labeled oligomer, a single TH mRNA of 1.9 kb was detected in adrenal gland and brain stem but not in liver and cerebral cortex. Using this TH-specific oligomer, TH mRNAs were localized to the chromaffin cells in the adrenal medulla and to catecholaminergic neurons in locus coeruleus and substantia nigra by in situ hybridization histochemistry. After reserpine administration, the intensity of hybridization signal was increased to threefold that of normal in sections of adrenal medulla and twofold that of normal in locus ceruleus. No difference in hybridization signal intensity was observed in the substantia nigra of normal and reserpine treated animals. Use of this specific TH probe in in situ hybridization procedures represents a powerful approach to the study of regulation of TH gene expression at the cellular level. PMID- 2883325 TI - [Antigenicity study of terazosin]. AB - Antigenicity of terazosin was studied in the experimental animals and the following results were obtained. Terazosin was shown to be non-immunogenic in guinea-pigs and mice when immunized alone or with mixture of terazosin and protein as immunogen. Protein-conjugate of terazosin induced responses of hapten specific antibody when guinea pigs and mice were immunized. However, terazosin alone was shown to be not capable of eliciting any allergic responses. In conclusion, terazosin lacks immunogenicity and eliciting antigenicity in these experimental conditions and this suggests that drug allergic response would either not occur or be minimal, if any, when terazosin is administered clinically. PMID- 2883326 TI - [Traumatic injuries of primary and young permanent anterior teeth]. PMID- 2883327 TI - Identification and mapping of human papillomavirus type 1 RNA transcripts recovered from plantar warts and infected epithelial cell cultures. AB - Multiple spliced transcripts of human papillomavirus type 1 were detected by electron microscopic analysis of R-loops formed with total RNA extracted from plantar warts and with poly(A)+ RNA isolated from cultured keratinocytes infected with human papillomavirus type 1. The 5' ends of the RNAs were mapped to sites in the E7 open reading frame (ORF), just upstream of the E6 ORF and in the upstream regulatory region. Species with 5' ends in E7 accounted for over 95% of all transcripts seen. Two polyadenylation sites were used, one at the end of the early (E) region of the viral DNA, the other at the end of the late (L) region. The most abundant species had a short 5' exon of approximately 100 nucleotides spanning the junction of the E7 and E1 ORFs spliced to a 3' exon of 800 nucleotides in the region with overlapping E2 and E4 ORFs; it was polyadenylated at the end of the E region. This species probably encodes the abundant E4 protein found in plantar warts (F. Breitburd, O. Croissant, and G. Orth, Cancer Cells, vol. 5, in press; J. Doorbar, D. Campbell, R. J. A. Grand, and P. H. Gallimore, EMBO J. 5:355-362, 1986). Other transcripts had exons spanning the E6-E7 ORFs, the E4-E5-L2-L1 ORFs, or the L1 ORF. The infrequent L1 transcript, probably the mRNA coding for the major capsid protein, had the same 5' exon in E7 as the abundant mRNA spliced from E1 and E4 ORFs, suggesting genetic regulation via the choice of the alternative polyadenylation sites or mRNA processing. PMID- 2883330 TI - Transmission of HTLV-I and HIV among homosexual men in Trinidad. AB - Risk for human T-cell lymphotropic virus type (HTLV-I) and human immunodeficiency virus (HIV) infection was evaluated in 100 homosexual or bisexual men from Trinidad. High seropositivity for HTLV-I (15% vs 2.4% in the general population) was linked to duration of homosexuality and numbers of partners, suggesting that HTLV-I, like HIV, can be transmitted by homosexual sex. Forty percent of homosexuals compared with 0.19% of the general population were seropositive for HIV, and sexual contact with US homosexual men and prior history of gonorrhea were major risk factors. The seroprevalence of HIV was three times higher than that for HTLV-I, suggesting that HIV is more efficiently transmitted, especially since HIV appears to have been recently introduced into Trinidad. Altered immune status was prominent in individuals infected with HIV and coinfected with HIV and HTLV-I. Whether HIV/HTLV-I coinfection amplifies clinical effects is a hypothesis that will require further evaluation. PMID- 2883329 TI - Stimulation of expression of the human endogenous retrovirus genome by female steroid hormones in human breast cancer cell line T47D. AB - Expression of the human endogenous retrovirus genome HERV-K, homologous to mouse mammary tumor virus, was investigated in cultured human tumor cells. In several cell lines, the HERV-K genome was expressed as an 8.8-kilobase poly(A)+ RNA which appeared to be a full-size transcript of this genome. In the human breast cancer cell line T47D, stimulation of HERV-K genome expression by progesterone was observed after estradiol treatment. PMID- 2883328 TI - Creation of a chimeric oncogene: analysis of the biochemical and biological properties of v-erbB/src fusion polypeptide. AB - A novel gene was created that linked complementary portions of two different tyrosine kinase oncogenes: v-erB and v-src. The v-erbB/src chimera encoded a glycoprotein exhibiting the subcellular distribution of the v-erbB protein but containing the kinase catalytic domain of the v-src parent. Fibroblasts expressing the v-erbB/src gene product became transformed to an oncogenic state and closely resembled cells expressing the v-erbB parent oncogene. Our results indicated that v-erbB sequences can be functionally replaced by sequences derived from a different oncogene, v-src, and that important determinants of the transformed phenotype appear to be encoded in oncogene sequences distinct from those defining the kinase catalytic domain itself. PMID- 2883332 TI - Comparative study of tiapride and neuroleptics with anti-dopamine activity on convulsive seizure in mice. AB - The effects of tiapride on the convulsive seizures induced by pentylenetetrazole, strychnine, picrotoxin and bemegride, and on electric seizure are reported and compared with those of sulpiride, chlorpromazine, haloperidol and reserpine. The number of deaths and intensity of convulsion increased dose-dependently and also with the increase in amplitude of electric shock. Tiapride and a similar compound, sulpiride, did not affect these seizures, whereas chlorpromazine potentiated strychnine-induced and electric seizure. Haloperidol and reserpine potentiated electric seizure, and chlorpromazine and reserpine tended to potentiate bemegride-induced seizure. Reserpine also tended to potentiate pentylenetetrazole-induced seizure. These results suggest that tiapride would be clinically safer than other drugs with anti-dopamine activity, except for sulpiride. PMID- 2883331 TI - Neurochemical characterization of cysteine sulfinic acid, an excitatory amino acid, in hippocampus. AB - In this communication, I have summarized our studies on the possible roles of cysteine sulfinic acid (CSA) in the central nervous system (CNS), from these observations, CSA was suggested to be a neurotransmitter. We reported the presence of CSA in the CNS and subsequently characterized Na+-dependent high affinity uptake and depolarization-induced release of CSA. Depolarization-induced release of [14C]CSA from the preloaded hippocampal slices was specifically attenuated by benzodiazepines and GABA agonists. Synaptic membranes have a Na+ dependent specific binding site for cysteic acid, an analogue of CSA, which may be a possible binding site for CSA. This binding site seemed to be distinct from that for glutamate. To assess CSA as a physiologically active candidate which is distinct from glutamate, two neurochemical experiments were performed: one experiment determined the enhancement by excitatory amino acids of depolarization induced release of [3H]GABA from the preloaded slices, and the other one monitored the cyclic AMP formation by excitatory amino acids in hippocampal slices. In both studies, differences in the responses to the various antagonists indicate that CSA receptors are distinct from glutamate receptors. Furthermore, we proposed that excitatory amino acid receptors which are subsequently linked to adenylate cyclase are functionally related to the Cl- channel. PMID- 2883333 TI - Lack of effects of carbachol on the Na-Ca exchange mechanism in frog atrial muscle treated with goniopora toxin. AB - Carbachol (CCh) at a concentration of 10(-7) M completely inhibited the twitch contraction of frog atrial muscle. However, when the preparation was treated with goniopora toxin (GPT), a selective inhibitor of Na channel inactivation, and the twitch contraction was augmented through the activation of Na-Ca exchange by this toxin, the reduction in contractile amplitude by CCh was only about 30% even at higher concentrations. The maximum rate of rise of the twitch contraction was not affected by CCh in GPT-treated preparations. The time course of configuration change of the twitch contraction after application of CCh in GPT-treated muscle indicated that the attenuation of amplitude preceded the shortening of duration. The residual contraction under the combined treatments with GPT and CCh was abolished by removal of external Ca++ or addition of TTX. CCh only moderately shortened the action potential which was prolonged by GPT, and further addition of TTX abolished the action potential. From these results, we suggest that CCh does not influence the twitch contraction which is augmented via the activation of the Na-Ca exchange mechanism in frog atrial muscle. PMID- 2883334 TI - Possible involvement of the CCK receptor in the benzodiazepine antagonism to CCK in the mouse brain. AB - In mice, intraperitoneally injected chlordiazepoxide and proglumide, both of which are regarded as cholecystokinin (CCK) receptor antagonists in the peripheral tissues, dose-dependently inhibited the satiety induced by 200 ng of intracisternally administered CCK octapeptide (CCK8). Intraperitoneally administered diazepam (1 mg/kg) and/or Ro 15-1788 (5 mg/kg), a benzodiazepine antagonist, both prevented the elevation in the pain threshold induced by 1 microgram of CCK8. However, Ro 15-1788 did not antagonize the effect of diazepam that reversed the CCK-induced antinociception. Ro 15-1788 also inhibited the satiety induced by CCK8. From these results, it was considered that the antagonism, which was observed in the present work, of benzodiazepines and proglumide to CCK8 seemed to occur at the CCK receptor and not at the benzodiazepine receptor in the brain. PMID- 2883335 TI - Influence of (-)-sulpiride and YM-09151-2 on stereotyped behavior in chicks and catalepsy in rats. AB - In this paper, the effects of three antipsychotic agents using the avian species laboratory model are described. d-Amphetamine (2-5 mg/kg, s.c.) dose-dependently antagonized catalepsy induced by haloperidol (0.25 mg/kg, i.p.), YM-09151-2 (0.02 0.04 mg/kg, i.p.) and (-)-sulpiride (20-40 mg/kg, i.p.) in rats. (-)-Sulpiride (10-40 mg/kg, i.p.) dose-dependently antagonized apomorphine (0.125 mg/kg, s.c.) induced stereotyped behavior in young chicks. Similarly, YM-09151-2 (0.04 mg/kg, i.p.) antagonized apomorphine (0.125 mg/kg, s.c.)-induced stereotyped behavior in young chicks. (-)-Sulpiride (40 mg/kg, i.p.) significantly antagonized apomorphine (0.25 mg/kg, s.c.)-induced stereotyped behavior in 6 week old chicks. Parachlorophenylalanine (PCPA, 300 mg/kg, i.p.) significantly reduced the intensity of stereotyped behavior induced by apomorphine (0.125 mg/kg, s.c.) in young chicks. However, (-)-sulpiride (40 mg/kg, i.p.) did not significantly influence the effect of PCPA on apomorphine-induced stereotyped behavior. Similarly, catalepsy induced by (-)-sulpiride (40 mg/kg, i.p.), haloperidol (0.25 mg/kg, i.p.) and YM-09151-2 (0.04 mg/kg, i.p.) in male rats was profoundly suppressed by PCPA (300 mg/kg, i.p.). The present results indicate that apomorphine-induced stereotyped pecking in young (4-6 day old) chicks may serve as a suitable laboratory model for testing potential antipsychotic drugs. In addition, the data indicates that endogenous 5-hydroxytryptamine mechanisms may be involved in the genesis of drug-induced catalepsy in rats. PMID- 2883336 TI - Effects of betaxolol, a new beta 1 selective blocker, on canine ventricular arrhythmias. AB - Antiarrhythmic effects of a new beta 1 selective adrenoceptor blocker, betaxolol, were examined in comparison with those of atenolol using two canine ventricular arrhythmia models (adrenaline arrhythmia and digitalis arrhythmia). Both betaxolol and atenolol suppressed adrenaline arrhythmia, and the minimum effective plasma concentration of betaxolol for this arrhythmia model was determined to be less than 10 ng/ml. However, on digitalis arrhythmia, both beta blockers were ineffective, even though the high doses used in these experiments, 3 mg/kg for betaxolol and 5 mg/kg for atenolol, showed significant hypotensive effects. The present results suggest that betaxolol and atenolol may be expected to be clinically effective on arrhythmias related to increased sympathetic tone. PMID- 2883337 TI - Modulatory action of prostaglandin D2 on the release of 3H-norepinephrine from rat cerebellar slices. AB - The modulatory action of prostaglandin D2 (PGD2) on the high-K+-induced release of 3H-norepinephrine (3H-NE) from rat cerebellar slices was investigated in relation to the presynaptic feedback mechanisms for the NE release. PGD2 (10(-7) 10(5) M) dose-dependently suppressed the release of 3H-NE. The 3H-NE release was also dose-dependently decreased by 10(-10)-5 X 10(-9) M clonidine and increased by 10(-9)-10(-6) M yohimbine, and there was an antagonism between clonidine and yohimbine, indicating the presence of an alpha 2-adrenoceptor-mediated negative feedback mechanism in the rat cerebellum. The inhibitory action of clonidine was not additive to that of PGD2, while there appeared to be an additiveness between the effects of PGD2 and yohimbine. The 3H-NE release was increased by I isoproterenol and decreased by I-propranolol, but only at concentrations higher than 10(-6) M. PGD2 nearly abolished the actions of these beta-adrenergic agents, and the 3H-NE release remained at a level similar to that induced by 10(-5) M PGD2 alone. Based on these results, it was tentatively suggested that PGD2 inhibits the 3H-NE release by a mechanism independent of adrenoceptor-mediated feedback mechanisms. PMID- 2883338 TI - [Studies on gamma-glutamyltranspeptidase in warm ischaemic kidneys of rats]. PMID- 2883339 TI - Alteration in dipeptidyl peptidase activities in cultured human carcinoma cells. AB - For the investigation of the possibility of its being a marker enzyme for tumor cells, the activity of dipeptidyl peptidase (DPP) IV (EC 3.4.14.5), a membrane bound enzyme, in cultured human carcinoma cells was examined. The homogenates of three carcinoma cell lines (HeLa, KB, and K-44) contained lower glycylprolyl methylcoumarinamide (Gly-Pro-MCA) hydrolase activities at pH 8.7 (assumed to be DPP IV) and higher activities of alkaline phosphatase and gamma-glutamyl transpeptidase, which are also membrane-bound enzymes, than those of normal human fibroblasts (HF). Examination of carcinoma cells for the subcellular localization and pH optimum of Gly-Pro-MCA hydrolase activity revealed that the activity of a lysosomal enzyme that hydrolyzes Gly-Pro-MCA at pH 6.4 was markedly increased in carcinoma cells, but not in normal cells. The separation and characterization of Gly-Pro-MCA hydrolases by gel filtration, affinity chromatography, and substrate specificity demonstrated that HF have three peaks indicating DPP IV, DPP II, and an unknown enzyme, whereas the three carcinoma cell lines gave a prominent peak indicating DPP II and a trace of DPP IV. The DPP II activity was 6- to 24-fold higher in carcinoma cell lines than in HF, and it also was 2.85- to 4.13-fold higher than the DPP IV activity in carcinoma cell lines but was 10-fold lower in HF. These clear enzymatic differences between carcinoma cells and normal HF may be useful as a marker of malignancy. PMID- 2883340 TI - [Combined extracorporeal detoxification of the blood and lymphatic drainage in hemorrhagic fever with renal syndrome]. PMID- 2883341 TI - [Use of beta-adrenoblockers in the treatment of acute myocardial infarct patients]. PMID- 2883342 TI - Massive hemolysis in Clostridium perfringens infections. AB - Over a 14-month period at the Cleveland Clinic Foundation, 424 strains of Clostridium were isolated; of these, 52 strains were Clostridium perfringens isolated from 41 patients. Eight strains of C. perfringens were isolated from the blood of six patients; five of these patients had neoplastic disease and three developed massive intravascular hemolysis with rapidly developing shock and death. Clinical details are given on three patients with fatal Clostridium perfringens sepsis, and the nature of presentation and pathophysiologic mechanisms are discussed. PMID- 2883343 TI - Antipsychotic drugs: prediction of side-effect profiles based on neuroreceptor data derived from human brain tissue. AB - The affinities of antipsychotic agents for neurotransmitter receptors are believed to be responsible for their antipsychotic activity and side-effect profiles. Data on neuroreceptor affinity can be used to predict side-effect profiles of antipsychotic drugs. In this report, we present data on receptor affinity that have been modified to help clinicians clearly see the potential for each drug to produce a specific side effect at any dosage. PMID- 2883344 TI - Risk of hypoglycaemia with alternate-day growth hormone injections. AB - Fasting hypoglycaemia developed in three growth hormone deficient children after the start of treatment with synthetic growth hormone. The effects, which occurred 36-60 h after each injection, may have been due to insulin-like effects of endogenous somatomedins after waning of insulin antagonism induced by growth hormone. Daily growth hormone injections may be necessary to maintain normal plasma glucose levels in young children. PMID- 2883345 TI - Dermatomyositis, polymyositis, and Coxsackie-B-virus infection. AB - Coxsackie-B-virus-specific probes prepared by reverse transcription of purified virus genomic RNA and molecular cloning techniques were used in quantitative slot blot hybridisations to test for the presence of virus RNA in skeletal muscle biopsy samples. The samples tested were from two patients with adult polymyositis, seven with juvenile dermatomyositis, four with Duchenne muscular dystrophy, and six normal controls. Of the nine patients with inflammatory muscle disease, five were positive for Coxsackie-B-virus RNA; no viral sequences were found in the ten Duchenne muscular dystrophy and control biopsy samples. PMID- 2883347 TI - Alzheimer's disease, Down's syndrome, and chromosome 21. PMID- 2883348 TI - Brain transplant for Parkinson's disease. PMID- 2883346 TI - Hypothyroidism as a cause of acquired von Willebrand's disease. AB - Three patients with bleeding tendency who met the criteria for type 1 von Willebrand's disease are described. In two patients, hypothyroidism was suspected and confirmed at presentation, and in the third hypothyroidism became apparent 4 years later. In all three, the history and clinical course after treatment with thyroxine indicated acquired von Willebrand's disease secondary to hypothyroidism. The possibility of hypothyroidism should be considered in patients presenting with von Willebrand's disease. PMID- 2883349 TI - Repeated oral activated charcoal in acute poisoning. PMID- 2883350 TI - Pancreatic transplantation in diabetes. PMID- 2883351 TI - Immunity to schistosomiasis. PMID- 2883352 TI - Man over monkey. PMID- 2883353 TI - Johne's and Crohn's. Chronic inflammatory bowel diseases of infectious aetiology? PMID- 2883354 TI - Minoxidil: hope for the bald? PMID- 2883355 TI - Prevention of hypoxaemia during upper-gastrointestinal endoscopy by means of oxygen via nasal cannulae. AB - Hypoxaemia during oesophagogastroduodenoscopy is well documented and contributes to cardiac arrhythmias and occasional deaths from endoscopy. In 50 patients sedated with intravenous midazolam and examined with a large-diameter endoscope, oxygen desaturation was abolished by giving oxygen (2 litres/min) by way of nasal cannulae throughout the procedure. PMID- 2883357 TI - Rhamnolipid of Pseudomonas aeruginosa in sputum of cystic fibrosis patients. PMID- 2883356 TI - Absence of electrochemical defect of cystic fibrosis in transplanted lung. PMID- 2883358 TI - Activated charcoal for carbamazepine poisoning. PMID- 2883359 TI - Uptake of aluminium into central nervous system along nasal-olfactory pathways. PMID- 2883360 TI - Antibody-dependent enhancement of dengue 2 virus in people of white descent in Cuba. PMID- 2883361 TI - Decline in sensitivity of Plasmodium falciparum to chloroquine in The Gambia. PMID- 2883362 TI - Dose-ranging study of ivermectin in treatment of filariasis due to Wuchereria bancrofti. PMID- 2883363 TI - Renal cell carcinoma and acquired cystic kidney disease after renal transplantation. PMID- 2883364 TI - Coronary heart disease mortality rates. PMID- 2883365 TI - Long-term delta antigenaemia without appearance of delta antibody in two immunodeficient patients. PMID- 2883366 TI - Drug-induced Parkinson's disease. PMID- 2883367 TI - Trials in acute stroke. PMID- 2883368 TI - Proptosis and neurofibromatosis. PMID- 2883369 TI - Botulism and Guillain-Barre syndrome. PMID- 2883370 TI - Visions that talk. PMID- 2883371 TI - Early embryo loss. PMID- 2883372 TI - Acute renal failure after use of granulated sugar in deep infected wound. PMID- 2883373 TI - Biological activity of intravenous immunoglobulins. PMID- 2883375 TI - Waiting lists. PMID- 2883374 TI - Confidence intervals. PMID- 2883376 TI - Yesterday's unwanted babies: today's teenage pregnancies. PMID- 2883377 TI - Circulating anti-neutrophil antibodies in systemic vasculitis. PMID- 2883378 TI - Deficient prostacyclin formation after acute myocardial infarction. PMID- 2883379 TI - Neonatal screening for hypercholesterolaemia. PMID- 2883381 TI - Herbal medicine precipitating massive haemolysis. PMID- 2883380 TI - Effect of hormone implants on psychological disorders in the climacteric. PMID- 2883382 TI - Ciprofloxacin penetration into lungs. PMID- 2883383 TI - Surfactants in severe hyaline membrane disease. PMID- 2883385 TI - Griseofulvin teratology. PMID- 2883384 TI - Prevention of periventricular haemorrhage. PMID- 2883386 TI - Oral contraceptives and breast cancer. PMID- 2883387 TI - Perinatal infection with cryptosporidium. PMID- 2883388 TI - Impairment of renal function after generalised seizures. PMID- 2883389 TI - Retinoblastoma and deletions of chromosome 13. PMID- 2883390 TI - Doctor's duty of care to give advice in therapeutic and non-therapeutic contexts. PMID- 2883391 TI - The myocardium in ankylosing spondylitis. A clinical, echocardiographic, and histopathological study. AB - Cardiac function was investigated in men with ankylosing spondylitis (AS) age 21 65 years who had no cardiorespiratory symptoms or known abnormalities of heart or lungs. Chest radiographs and standard electrocardiograms were normal in 73 of 74 subjects. In echocardiographs of 30 men, left atrial size and left ventricular cavity size and wall thickness were normal. Minor abnormalities in the valve roots were present in 3 older men. Early diastolic abnormalities of the left ventricle were demonstrated in 16 of 30 subjects. This finding was confirmed by repetition of the echocardiography a year later in 15 subjects and by comparison of 11 probands with their healthy brothers. Myocardial tissue obtained at necropsy from 28 AS patients without ischaemic or valvular heart disease or hypertension was studied. A mild, diffuse increase of interstitial connective tissue was seen but there was no inflammatory change or amyloid. Computerised image analysis showed 30.7% interstitial reticulin compared with 17.7% in age/sex matched controls (p less than 0.0001). PMID- 2883392 TI - Association of different allelic forms of group specific component with susceptibility to and clinical manifestation of human immunodeficiency virus infection. AB - The distribution of phenotypes of the group specific component (Gc) was examined in 203 homosexuals at risk of infection or infected by the human immunodeficiency virus and compared with that in 50 randomly selected homosexuals and 122 healthy male heterosexual seronegative controls. 30.2% of patients with the acquired immunodeficiency syndrome (AIDS) were homozygous for Gc 1 fast (Gc 1f) compared with 0.8% of controls (p less than 0.0001); patients with other clinical manifestations of HIV infection were also more likely than controls to have Gc 1f. By contrast, seronegative symptomless homosexual contacts of AIDS patients (AH-p) lacked this phenotype but were more likely than controls to be homozygous for Gc 2 (25% vs 9%, p less than 0.05). AIDS patients lacked the homozygous Gc 2 phenotype altogether. A chi 2 trend test showed that progression to AIDS had a strong positive association with the Gc 1f allele (p less than 0.0001) and a negative one with Gc 2 (p less than 0.05). It is proposed that Gc may be involved in viral entry into host cells, the ease of which varies with different allelic forms of Gc, according to their sialic acid content. PMID- 2883394 TI - Reversible hypertension associated with unrecognised high pressure chronic retention of urine. AB - The cardiovascular effects of relief of obstruction were examined in 21 patients with painless urinary retention and hydronephrosis and hydroureter associated with hypertension (diastolic blood pressure 95-120 mm Hg, mean 107, 11 patients), severe peripheral oedema (8 patients), raised jugular venous pressure (5 patients), or clinical evidence of pulmonary oedema (5 patients). Before relief of obstruction fractional sodium excretion was appropriate for the reduced rate of glomerular filtration. After urethral catheterisation blood pressure fell (p less than 0.001) and the other cardiovascular abnormalities were rapidly reversed without further therapeutic measures. This improvement was associated with an increase (p less than 0.05) in both absolute and fractional urinary sodium excretion that was greatest at 24 h. 5% of patients undergoing surgery for obstructive disorders of the lower urinary tract have hydronephrosis and hydroureter. Hypertension related to chronic urinary tract obstruction may be the commonest form of surgically correctable renal hypertension. PMID- 2883393 TI - Large-scale field trial of Ty21a live oral typhoid vaccine in enteric-coated capsule formulation. AB - Three doses, given within one week, of Ty21a attenuated Salmonella typhi oral vaccine in an enteric-coated formulation provided 67% efficacy for at least 3 years in a randomised, placebo-controlled field trial involving 109,000 schoolchildren in Santiago, Chile. Increasing the interval between doses to twenty-one days did not enhance protection. Significantly less protection followed administration of vaccine in gelatin capsules with sodium bicarbonate. Ty21a provides the same level of protection as the heat/phenol-inactivated whole cell parenteral vaccine but differs in not causing adverse reactions. Ty21a may now be regarded as a practical public health tool. PMID- 2883395 TI - Predictive value of lectin binding on breast-cancer recurrence and survival. AB - A new approach for predicting long-term survival of breast-cancer patients is the detection of carbohydrate expression in paraffin-embedded sections of the primary tumour. The binding of a lectin (HPA), derived from the albumin gland of the Roman snail, Helix pomatia, to N-acetyl-galactosaminyl oligosaccharides appears valuable in assessing long-term prognosis. The clinical progress of 179 patients, followed-up for 15-20 years, was related to staining of paraffin sections of their primary breast cancers by HPA. All patients had had mastectomy but were not stratified by pathology or treatment. There were significant differences, in premenopausal patients, between groups with and without HPA staining in both time to first recurrence and survival time. HPA binding provides an extra tool for staging to aid decisions in early adjuvant treatment, with the advantage of being applicable to routinely fixed paraffin-embedded material. PMID- 2883396 TI - Coronary artery infusion of neuropeptide Y in patients with angina pectoris. AB - Neuropeptide Y was infused into a coronary artery of 6 patients with typical angina but no significant coronary stenosis. 3 patients had transient myocardial ischaemia, shown by typical pain and electrocardiographic change, at doses of 0.2 pmol/kg per min in 2 patients and 1.0 pmol/kg per min in 1 patient. The arteriographic appearances suggested constriction of small vessels rather than constriction of epicardial coronary arteries. The ischaemia was completely reversed by intracoronary administration of isosorbide dinitrate with no adverse sequelae. This is the first demonstration of myocardial ischaemia in man induced by a peptide neurotransmitter. PMID- 2883397 TI - Diagnosis of type 1a and type 1c glycogen storage diseases in adults. AB - The hepatic glucose-6-phosphatase system was studied with a novel microanalytical technique in adult patients undergoing liver biopsy. 4 patients were diagnosed as having type 1 glycogen storage disease (GSD). 3 of these patients, who had hypoglycaemic symptoms, had variations of type 1a GSD, which is caused by a defect in the hepatic microsomal glucose-6-phosphatase enzyme. The fourth, with hepatomegaly and no hypoglycaemic symptoms, had a normal glucose-6-phosphatase enzyme but a defect in the hepatic microsomal phosphate/pyrophosphate translocase T2; this is the first report of an adult with type 1c GSD. Adult type 1 GSD should be considered in patients with unresolved hypoglycaemic symptoms and/or unresolved hepatomegaly. PMID- 2883398 TI - Haemorrhagic colitis and Vero-cytotoxin-producing Escherichia coli in England and Wales. AB - Vero-cytotoxin-producing strains of Escherichia coli (VTEC) were identified by the use of DNA probes in 39% of faecal samples from patients with haemorrhagic colitis in England and Wales. The patients with VTEC were distributed widely and their ages ranged from 2.5 to 86 years (mean 41). 3 patients died, including a child of 2.5 years. 30 of the 32 VTEC strains belonged to serogroup O157. Plating on sorbitol agar for non-fermenters followed by agglutination with a specific O157 antiserum was a useful screening method for O157 VT+ strains. However, it was not as sensitive as the DNA probe technique and did not detect VTEC of other serogroups. PMID- 2883399 TI - Vitamin A for measles. PMID- 2883400 TI - Management of drug addicts: hostility, humanity, and pragmatism. PMID- 2883401 TI - Select committee report on primary health care. PMID- 2883403 TI - Surgical training in the UK for doctors from overseas. PMID- 2883402 TI - Gilbert's syndrome--more questions than answers. PMID- 2883404 TI - Assessing disease activity in ankylosing spondylitis. PMID- 2883405 TI - Is it possible to predict the minimum size of the acquired immunodeficiency syndrome (AIDS) epidemic in the United Kingdom? AB - A mathematical model of the dynamics of transmission of human immunodeficiency virus within the male homosexual population in the United Kingdom demonstrates that even the minimum size of the acquired immunodeficiency syndrome (AIDS) epidemic in the United Kingdom (based upon the assumption that all transmission ceased at the end of 1986) is difficult to predict. Model predictions are particularly sensitive to assumptions about the distributed incubation period of the disease, differences in frequency and patterns of sexual activity, and the proportion of infected people in whom AIDS later develops. More accurate predictions will depend on the collection of data on the incubation period of the disease, the infectiousness of infected persons, and on the numbers of new sexual partners of each sex per person and the duration of each partnership. PMID- 2883406 TI - High-dose versus low-dose intravenous immunoglobulin in hypogammaglobulinaemia and chronic lung disease. AB - In a randomised cross-over study 12 patients with antibody deficiency and chronic lung disease received monthly infusions of either 0.6 g/kg or 0.2 g/kg intravenous immunoglobulin for six months, and were then switched to the alternative dose for a further six months. Although the incidence of infections did not differ greatly in the high-dose and low-dose phases, the frequency of acute infection was substantially reduced in those periods when serum IgG was 500 mg/dl or more. Pulmonary function worsened on the low-dose regimen and improved on the high-dose regimen. PMID- 2883407 TI - Insulin and atheroma--an update. PMID- 2883408 TI - Asthma death due to ibuprofen. PMID- 2883409 TI - Acupuncture and asthma. PMID- 2883411 TI - Eicosapentaenoic acid. PMID- 2883410 TI - Acupuncture to prevent cisplatin-associated vomiting. PMID- 2883412 TI - Ovarian cysts: management by puncture? PMID- 2883413 TI - No evidence for general thallium poisoning in Guyana. PMID- 2883414 TI - Safety of chorionic villus sampling. PMID- 2883415 TI - Viruses detected in HTLV-I-associated myelopathy and adult T-cell leukaemia are identical on DNA blotting. PMID- 2883416 TI - Television endoscopy with prerecorded images for comparison. PMID- 2883418 TI - Clobetasol propionate ointment as first-aid for burns. PMID- 2883417 TI - Oral cancer in rural India. PMID- 2883419 TI - Bleeding associated with heparin contaminants. PMID- 2883420 TI - Subgroups of Legionella pneumophila serogroup 1. PMID- 2883421 TI - Central anticholinergic syndrome. PMID- 2883422 TI - Fatal rhabdomyolysis in marathon runner. PMID- 2883423 TI - Analgesia and anaesthesia in newborn babies and infants. PMID- 2883424 TI - Eurohealth. PMID- 2883425 TI - Fahraeus and erythrocyte sedimentation. PMID- 2883426 TI - Withholding unfavourable results in drug company sponsored clinical trials. PMID- 2883427 TI - Histiocytosis syndromes in children. PMID- 2883429 TI - AIDS and human milk bank closures. PMID- 2883428 TI - Complication of central venous catheterisation. PMID- 2883430 TI - Cryoprecipitate: a safe factor VIII replacement. PMID- 2883431 TI - Laboratory safety and HIV. PMID- 2883432 TI - Lack of HIV replication in arthropod cells. PMID- 2883433 TI - Effect of active and passive smoking on vascular reactivity in mothers and infants. PMID- 2883434 TI - Treatment failure of ofloxacin in Campylobacter pylori infection. PMID- 2883435 TI - Long-term survival of women diagnosed with breast cancer 1936-50. PMID- 2883436 TI - Bereavement and severe dementia. PMID- 2883437 TI - Psychologically determined death in anorexia nervosa. PMID- 2883438 TI - Endotracheal adrenaline in cardiac arrest. PMID- 2883439 TI - Measures of nutritional status. PMID- 2883440 TI - Vaccination against Japanese encephalitis. PMID- 2883441 TI - House of Lords upholds decision to sterilise 17-year-old mentally handicapped girl. PMID- 2883442 TI - Prediction of rapid bone loss in postmenopausal women. AB - Bone loss was determined in 178 women in the early postmenopausal period by photon absorptiometry measurement of forearm bone mineral content (BMC) every 3 months for 2 years. With a sequential cut-off technique, the results of a single determination of body fat mass, urinary calcium and hydroxyproline, and serum alkaline phosphatase, carried out at the first examination, correctly identified 79% of "fast bone losers" (bone loss greater than 3% annually) and 78% of "slow bone losers". With this simple approach the majority of women at highest risk of osteoporotic fractures in later life can be identified in the early postmenopausal period and started on prophylactic hormone replacement therapy. PMID- 2883443 TI - Long-term outcome of treating rheumatoid arthritis: results after 20 years. AB - Outcome of therapy, in terms of functional capacity, radiological measures of joint damage, erythrocyte sedimentation rate (ESR), rheumatoid factor, and mortality, was determined prospectively in 112 consecutive rheumatoid arthritis (RA) patients treated for 20 years at one centre, where a policy of active treatment was pursued with the use of gold, chloroquine, steroids, and, in resistant cases, penicillamine or cytotoxic drugs. By 20 years 35% were dead. Mortality was often attributable to RA. Function improved in the early years of treatment but declined considerably between 10 and 20 years. At 20 years 19% were severely disabled. Radiographs showed related evidence of increasing joint destruction. The ESR and rheumatoid factor levels changed little. Age, late presentation, and rheumatoid factor seropositivity at presentation were poor prognostic factors. The concept of "remission-inducing" drugs is fallacious. Early treatment may be advantageous, but the prognosis of RA is not good. PMID- 2883444 TI - Beneficial effect of pre-transplant splenectomy on displacement bone marrow transplantation for Gaucher's syndrome. AB - 2 patients with fast and 4 with medium varieties of Gaucher's syndrome were treated by displacement bone marrow transplantation to install a donor enzyme factory for life. Immunoprophylaxis was given to prevent host impairment of normal enzymes. 5 patients showed rapid and remarkable improvement and were leading fully active lives at 310-1207 days postgraft. Hypersplenism caused the death of 1 patient and a stormy time for another. Pre-transplant elective splenectomy hastened recovery. PMID- 2883445 TI - Selection-adjusted comparison of life-expectancy of patients on continuous ambulatory peritoneal dialysis, haemodialysis, and renal transplantation. AB - To investigate the controversy surrounding the life-expectancy of patients on continuous ambulatory peritoneal dialysis (CAPD) compared with that of patients on haemodialysis or transplantation mortality data from 389 patients accepted for renal replacement therapy in Leicester between July, 1974, and July, 1985, were retrospectively analysed with respect to a wide range of pre-treatment variables (6 scales and 115 binary variables), by a method (Cox's) that adjusts for the distorting influence of selection bias. 9 independent variables were identified as having a significant influence on survival. Adverse factors were age, amyloidosis, ischaemic heart disease, convulsions, and acute presentation. Beneficial variables were male sex, parenthood, pyelonephritis, and residence in Leicestershire. By correcting for the influence of these variables and using time dependent treatment co-variates, the bias adjusted estimates of the relative risk of death were 1 for patients on CAPD, 1.30 for those on haemodialysis, and 1.09 for patients who received transplants. These risks do not differ significantly from one another and suggest that CAPD is at least as effective as haemodialysis or transplantation at preserving life. PMID- 2883446 TI - Mapping the human genome. PMID- 2883447 TI - Vitamin D: new perspectives. PMID- 2883448 TI - Long-term EEG monitoring in epilepsy. PMID- 2883450 TI - Born 1837, still going strong. PMID- 2883449 TI - Uric acid in hypertension. PMID- 2883451 TI - A testing time for test-tube babies. PMID- 2883452 TI - Who needs molar units for drugs? AB - The standardisation of units for drug concentration measurement in clinical medicine is an urgent necessity. The obvious choice is mass units based on the litre. A change to molar units for drug concentrations would make no sense unless drugs were also prescribed in moles, which would cause disruption and inconvenience. There would be considerable danger to patients and the change would be expensive. Most importantly, molar units for drugs will not benefit doctors or their patients. Mass units should be retained and proposals for the adoption of molar units should be abandoned. PMID- 2883454 TI - Some pains I have known. PMID- 2883453 TI - Yersinia enterocolitica infections and pork: the missing link. AB - To determine the risk factors for Yersinia enterocolitica (YE) infection in Belgium, which is the country with the highest incidence of this infection, 40 persons with YE infections due to serotype O:3 (n = 36) or O:9 (n = 4) were compared with matched controls. Most patients had acute gastroenteritis; 1 had a liver abscess. 20% were admitted to hospital; the mean duration of hospital stay was 9 days. YE infection was strongly associated with eating raw pork in the 2 weeks before onset (odds ratio = 12, p = 0.00002), a factor that accounted for 58% of the YE infections studied. 14 (18%) of 79 families surveyed at a well-baby clinic fed their children raw pork from a median age of 18 months. Specific control measures to reduce contamination and consumption of raw pork may reduce the incidence of YE infections. PMID- 2883455 TI - Qualms about QALYs. PMID- 2883456 TI - Premenopausal hysterectomy and risk of cardiovascular disease. PMID- 2883457 TI - Clinical presentation of Schistosoma intercalatum infestation. PMID- 2883458 TI - Hypnosis for intractable vomiting. PMID- 2883459 TI - Optic glioma in children with neurofibromatosis. PMID- 2883460 TI - Serological screening for Campylobacter pylori in candidates for renal transplantation. PMID- 2883461 TI - Urine and faecal IgA response during naturally acquired infection with Campylobacter jejuni. PMID- 2883462 TI - CAPD peritonitis. PMID- 2883463 TI - Nutrition and oesophageal cancer. PMID- 2883464 TI - Osteoarthritis after blood-glucose self-monitoring. PMID- 2883465 TI - Complement activation in progressive systemic sclerosis. PMID- 2883466 TI - Human parvovirus and fetal anaemia. PMID- 2883467 TI - Exposure to Chlamydia psittaci in pregnancy. PMID- 2883468 TI - Fatigue and fatigability. PMID- 2883469 TI - Radiation and cancer epidemiology. PMID- 2883470 TI - Boycotts and medicine. PMID- 2883471 TI - Urine testing and drug abuse. PMID- 2883473 TI - Encouraging breastfeeding. PMID- 2883472 TI - The process of diagnosis. PMID- 2883474 TI - Student numbers and medical manpower. PMID- 2883475 TI - Yersinia infection and acute abdominal pain. PMID- 2883476 TI - Voluntary licensing and IVF/ET. PMID- 2883477 TI - Visual evoked responses and oligoclonal bands in multiple sclerosis. PMID- 2883478 TI - Radiation recall and radiosensitization with alkylating agents. PMID- 2883479 TI - Routes of HIV-2 transmission in western Europe. PMID- 2883480 TI - HIV-2 in blood donors and in different risk groups in France. PMID- 2883481 TI - Seronegativity and paediatric AIDS. PMID- 2883482 TI - Heterosexual transmission of HIV infection. PMID- 2883483 TI - Breast cancer screening. PMID- 2883484 TI - Heart attacks and lowering of blood pressure. PMID- 2883485 TI - Lowered blood pressure and the J-shaped curve. PMID- 2883486 TI - Handedness in children with birthweights below 1000 g. PMID- 2883487 TI - National AIDS trust: Mr Maxwell seeks pounds 50 million. PMID- 2883488 TI - Doxycycline prophylaxis for falciparum malaria. AB - 188 schoolchildren aged 10-15 living in a malaria endemic area along the Thai Burmese border were matched for age, splenomegaly, and weight and were then randomly assigned to receive either doxycycline (adult equivalent of 100 mg daily) or chloroquine (adult equivalent of 300 mg base weekly). All drugs were administered by the investigators and blood smears were done weekly. In 95 subjects taking doxycycline for 597 man-weeks there were 5 cases of falciparum malaria and in the 93 controls taking chloroquine for 488 man-weeks there were 31. Doxycycline was more effective than chloroquine in the prevention of falciparum malaria infections (p less than 0.0001). The doxycycline group did not have significantly more side-effects than the chloroquine group. PMID- 2883489 TI - Infants born to mothers seropositive for human immunodeficiency virus. Preliminary findings from a multicentre European study. AB - As part of a project within the European Community research activities on acquired immunodeficiency syndrome (AIDS), infants born to human-immunodeficiency virus-seropositive mothers are being followed up from birth. By October, 1986, 71 infants from Padua, Berlin, and Edinburgh had been followed up to a median age of 6 months (range 1-15 months). Symptoms of AIDS or AIDS-related complex (ARC) had developed in 5, 3 of whom had died. The median age at antibody loss was during the 10th month. An estimated 75% will have lost maternal antibody by 12 months, but loss of antibody did not exclude infection confirmed by virus culture. Numbers were too small to draw conclusions about the risk of AIDS/ARC and mode of delivery or breast-feeding. The study suggested that the risk of AIDS/ARC is higher in infants born to mothers who have AIDS symptoms during pregnancy. PMID- 2883490 TI - Human-immunodeficiency-virus infections in infants negative for anti-HIV by enzyme-linked immunoassay. AB - Of 85 children with human-immuno-deficiency-virus (HIV) infection based on clinical (opportunistic infection), epidemiological (mother a drug addict or known to be HIV infected), and immunological (helper-T-cell deficiency and impaired proliferative response to pokeweed mitogen) features, 9 were found to lack antibody to HIV as measured by a commercial enzyme-linked immunoassay (ELISA). All 9 children had detectable levels of HIV antigen in simultaneous plasma specimens, measured by a sensitive antigen-capture ELISA. The use of the western blot assay and an ELISA with recombinant HIV antigens was able to identify HIV infection in 4 of the 9 children. PMID- 2883492 TI - LHRH analogues for contraception. PMID- 2883491 TI - Campylobacter pylori detected noninvasively by the 13C-urea breath test. AB - The high endogenous urease activity of Campylobacter pylori was exploited in a non-invasive test for the presence of this organism in the stomach. When 13C-urea was administered orally after a test meal, urea-derived 13CO2 appeared in the respiratory CO2 of infected individuals at a constant rate for greater than 100 min. The test was validated in 26 individuals who underwent both the 13C-urea breath test and endoscopic biopsy of the antral mucosa for culture and histological examination. Each positive breath test proved to be correlated with a positive culture or Warthin-Starry silver stain of a mucosal biopsy specimen, or both. PMID- 2883494 TI - Input and outcome. PMID- 2883493 TI - Hearing problems in elderly people: implications for services. PMID- 2883495 TI - Vaccines against leprosy. PMID- 2883496 TI - Sunburn and melanoma. PMID- 2883497 TI - Are hospital services rationed in New Haven or over-utilised in Boston? AB - The populations of New Haven and Boston are demographically similar and receive most of their hospital care in university hospitals, but in 1982 their expenditures per head for inpatient care were $451 and $889, respectively. The 685,400 residents of Boston incurred about $300 million more in hospital expenditures and used 739 more beds than they would have if the use rates for New Haven residents had applied. Most of the extra beds were invested in higher admission rates for medical conditions in which the decision to admit can be discretionary. The overall rates for major surgery were equal, but rates for some individual operations varied widely. These findings indicate that academic standards of care are compatible with widely varying patterns of practice and that medical care costs are not necessarily high in communities served largely by university hospitals. They also emphasise the need for increased attention to the outcome and cost implications of differences in practice styles. PMID- 2883498 TI - The new genetics: will it pay its way? AB - The number of genetic disorders detectable antenatally by the use of DNA probes has risen rapidly. The demand for diagnosis and termination of affected pregnancies in high-risk families is likely to increase as tests become more accurate and widely known. Each Regional Health Authority (RHA) must therefore urgently compare any financial savings to be made from a DNA diagnostic service with the cost of setting up and running a laboratory. There are great difficulties in conducting a formal cost-benefit analysis, but the pressing need for a cost appraisal made a more limited cost-savings approach necessary. This paper uses a broad-brush approach for all disorders and known costs for inpatient hospital care only. Despite the limitations of the method, in the two regions studied (North West and South East Thames) there would be clear savings at hospital level if a DNA screening laboratory were set up in each region. Funds released from treatment of genetic disorders could be used for other purposes. There are benefits to the families concerned, social service and educational savings, and other health service savings not considered here. On hospital costs alone there are benefits from the programme and wider consideration will make it more cost-effective. Once a programme is set up, new developments will make it even more cost-effective. It is concluded that RHAs should attach high priority to the setting up of such laboratories. PMID- 2883500 TI - Discordant priorities. PMID- 2883499 TI - Risk of unexplained stillbirth at different gestational ages. AB - In 40,635 deliveries in 1978-85, unexplained stillbirths were an important component (nearly a quarter) of all perinatal deaths. The rate of unexplained stillbirth (unexplained stillbirths divided by total births) was highest among preterm deliveries, fell to a minimum at 39-40 weeks' gestation, then rose at 41 42 weeks. Rate is generally accepted as measuring risk, but since it is the population of undelivered, not delivered, infants that is at risk of intrauterine death, stillbirth risk would be better measured as the number of impending stillbirths divided by the total number of undelivered fetuses. With this measure the risk of unexplained stillbirth was least in preterm pregnancies, rising fourfold after 39 weeks to a maximum at 41 weeks. At this time, it was also four times higher than at 33 weeks, in contrast to the rate, which was nineteen times lower. PMID- 2883501 TI - The right to drink. PMID- 2883502 TI - First results with ICS 205-930 (5-HT3 receptor antagonist) in prevention of chemotherapy-induced emesis. PMID- 2883503 TI - Sudden death in cocaine abusers: relation to neuroleptic malignant syndrome. PMID- 2883504 TI - Multiple sclerosis (not tropical spastic paraparesis) on Key West, Florida. PMID- 2883505 TI - Multiple sclerosis on islands. PMID- 2883506 TI - Seropositivity to HIV-1 and HIV-2. PMID- 2883507 TI - Thiamine deficiency, Wernicke's encephalopathy, and AIDS. PMID- 2883508 TI - False negative result by the wellcozyme anti-HIV assay in testing an HIV positive haemophiliac. PMID- 2883509 TI - Diabetes and end-stage renal failure. PMID- 2883510 TI - Specific antibody and virus antigen expression in congenital HIV infection. PMID- 2883511 TI - Eicosapentaenoic acid in fat. PMID- 2883513 TI - Trisomy 21 mosaicism and maternal age effect. PMID- 2883512 TI - Fatty acid pattern and ischaemic heart disease. PMID- 2883515 TI - Confidence in clinical tests. PMID- 2883514 TI - Danger of hypotonic half-Darrow's solution. PMID- 2883516 TI - Evaluation of a new blood glucose meter. PMID- 2883517 TI - Chernobyl and hypothyroidism. PMID- 2883519 TI - Irritable bowel syndrome. PMID- 2883518 TI - Timing of hepatitis B revaccination in healthy adults. PMID- 2883520 TI - Joggers grow old. PMID- 2883521 TI - Medical manpower and student numbers. PMID- 2883523 TI - Food irradiation. PMID- 2883522 TI - Europe against cancer. PMID- 2883524 TI - PROST for ovum donation. PMID- 2883525 TI - Low serum albumin and failure of fixation of hip fractures. PMID- 2883526 TI - Myoedema as a clinical sign in paralytic rabies. PMID- 2883527 TI - Chloroquine and hypoglycaemia. PMID- 2883528 TI - Myelosuppression after methotrexate, mitoxantrone, and mitomycin C. PMID- 2883529 TI - Halothane allergy as cause of acne. PMID- 2883530 TI - Psychiatric effects of steroids. PMID- 2883531 TI - Topical cyclosporin and immunologically-mediated skin disorders. PMID- 2883532 TI - Septic complications after chorionic villus sampling. PMID- 2883533 TI - Calcium solutions for cardiac resuscitation. PMID- 2883534 TI - Outcome for survivors from respiratory-distress syndrome. PMID- 2883535 TI - Pre-trial exchange of expert evidence to become normal practice in medical negligence actions. PMID- 2883536 TI - Causes of schizophrenia. PMID- 2883537 TI - [Causes and treatment of seasickness]. AB - Seasickness is usually induced by conflicting sensory cues. However, very little is known about the neural pathways and processes which play a role in the development of nausea. Since the symptoms, for example, pallor, sweating and vomiting are all of parasympathetic origin, the common antiemetic drugs are anticholinergically efficient. More recently, additional drugs and modified forms of application have been introduced to reduce the soporific side effects. It is pointed out that onboard behaviour and even choice of vessel can be of more importance than use of antivertiginous drugs. Besides attention to the individual adaptation to the atypical seagoing environment, simple behaviour patterns such as fixation on the horizon, avoiding of head movements and reduction of conflicting sensory cues can be very effective in reducing symptoms. PMID- 2883538 TI - [Anxiety and technics]. PMID- 2883539 TI - [Causes of coronary heart disease]. PMID- 2883540 TI - [Mortality, excess mortality, fatalities and the probability of survival]. PMID- 2883541 TI - [Mean age at death for selected causes of death and the mortality rate in West Germany 1958 and 1978]. PMID- 2883542 TI - [Acute natural death at public places in a large city]. PMID- 2883543 TI - [Increased occurrence of deaths due to hypothermia caused by surprise cold fronts]. PMID- 2883544 TI - [Previous injuries in private accident insurance]. PMID- 2883545 TI - [Rational pharmacotherapy of anxiety states]. PMID- 2883546 TI - Effects of chronic ethanol treatment on amino acid uptake and enzyme activities in the lactating rat mammary gland. AB - The effects of chronic ethanol consumption on mammary gland amino acid uptake at the 15th day of lactation in the rat have been studied. Ethanol treatment decreased the arterial levels of Ala, Asp, Gly, Pro, Lys and Met, and increased those of Gln and alpha-amino-butyrate. Chronic ethanol treatment produced a decrease in the arteriovenous differences of Asp, Thr, Arg, Met and Phe, and increased those of Ala, Gln, Gly, Pro and Tyr. The combination of the calculated values of relative extraction and the arteriovenous differences indicate that these alterations in amino acid uptake are related to changes in the transport process for Ala, Asp, Thr, Pro, Arg, Asn, Gly, Tyr, and Phe, and that the alterations in the arteriovenous differences of Gln, Lys and Met are due to the affected arterial levels of these amino acids. Measurements of enzymatic activities in the mammary gland show that these alterations in the amino acid transport process cannot be ascribed to changes in the gamma-glutamyl cycle. PMID- 2883547 TI - Regulation of somatostatin-14 and gastrin I binding sites in rat gastrointestinal mucosa by ulcerogenic dose of cysteamine. AB - A single duodenal ulcerogenic dose of cysteamine administered into rats induced time-dependent depletion of immunoreactive somatostatin in the gastric corporeal, antral, and duodenal mucosa with a parallel increase (up-regulation) of somatostatin binding sites. The concentration of somatostatin binding sites returned to the control level in the corporeal mucosa when measured at 24 hrs; however, in the duodenal mucosa there was only a partial return to the control level. Somatostatin binding sites in the antral mucosa did not return to control level even after 24 hrs. Except for the duodenum mucosal immunoreactive gastrin level was unaffected by cysteamine administration, but corporeal mucosal gastrin I binding sites were diminished (down-regulation) after 24 hrs. PMID- 2883549 TI - Glafenine-associated hepatic injury: 38 or 5 cases? PMID- 2883548 TI - Adrenoceptors and the pharmacology of affective illness: a unifying theory. AB - Based on recent clinical and preclinical research, it is theorized that antimanic and antidepressant effects of clinically available drugs can be produced through their actions on alpha-1 adrenoreceptor-mediated neurotransmission in the central nervous system. The theory suggests that final effects on alpha-1 mediated neurotransmission may be produced not only by drugs which have direct effects on the alpha-1 receptor or its second messenger, but also by drugs having effects on neurotransmitter systems such as acetylcholine, GABA, and serotonin, among others, which modulate the activity of central norepinephrine neurons or, via feedback mechanisms, by drugs having effects on adrenergic receptors other than the alpha-1 receptor itself. PMID- 2883550 TI - The right to refuse antipsychotic medication: who decides? PMID- 2883552 TI - [Plasma lipoproteins in alcoholic liver diseases]. PMID- 2883551 TI - Running-related injury prevention through barefoot adaptations. AB - A number of reports indicate an extremely low running-related injury frequency in barefoot populations in contrast to reports about shod populations. It is hypothesized that the adaptations which produce shock absorption, an inherent consequence of barefoot activity and a mechanism responsible for the low injury frequency in unshod populations, are related to deflection of the medial longitudinal arch of the foot on loading. It is also hypothesized that the known inability of this arch of the shod foot to deflect without failure (foot rigidity) is responsible for the high injury frequency in shod populations. To evaluate these hypotheses, 17 recreational runners were analyzed to study the adaptive pattern of the medial longitudinal arch of the foot due to increased barefoot weight-bearing activity. Changes occurred in the medial longitudinal arch which allowed deflection of this arch on loading which substantiated the hypotheses. Other evidence suggests that sensory feedback largely from the glabrous epithelium of the foot is the element of barefoot activity which induced these adaptations. The sensory insulation inherent in the modern running shoe appears responsible for the high injury frequency associated with running. The injuries are considered "pseudo-neuropathic" in nature. PMID- 2883553 TI - [Changes in the sensitivity of cardiovascular beta adrenergic receptors after sinoaortic denervation in rats]. PMID- 2883554 TI - [Effect of music on the general feeling of persons performing monotonous work]. AB - The investigation was aimed at checking the influence of music on subjective symptoms of workers carrying out monotonous work. The investigation was divided into two stages: without music and with music. The investigation covered 80 women employed as electronic equipment fitters, mean age 26.5, and average length of employment 4 years. The scale of subjective appraisal of general feeling was applied. Music transmitted at monotonous workplaces was found to eliminate of considerably decrease the intensity of unfavourable subjective felt symptoms induced by monotonous work. PMID- 2883555 TI - [Various aspects of the ecology of mosquitoes (Diptera, Culicidae) from a plains area (Calabria Farms) in Jacarepagua, Rio de Janeiro. V. Breeding grounds]. AB - Results are presented of observations on the breeding places of mosquitoes, carried out in a coastal lowland farm--Granjas Calabria, in Jacarepgua, city of Rio de Janeiro, Brazil. The majority of species preferred breeding places on the ground, chiefly the natural ones, but also developed in those originated from human activities. Cx. saltanensis and the species belonging to the Aedini tribe, such as Ae. scapularis, Ae. taeniorhynchus, Ps. ciliata, Ps. confinnis and Ps. pseudomelanota were more abundant in temporary breeding places, while Ma. titillans, Cx. amazonensis, Cx. chidesteri, Cx. bidens, Cx. declarator, Cx. nigripalpus and Cx. plectoporpe occurred usually in the permanent ones. Some species were collected in natural recipients: Cx. ocellatus, the Cx. (Microculex), Ph. davisi, Ph. deanei and Wy. forcipenis, in bromeliads; Ae. terrens, Cx. imitator and Cx. gairus, in tree-holes; and Wy. leucostigma, in the submerged Typha dominguensis leaf axils. Cx. gairus was found for the first time breeding in artificial containers, which were also preferred by Cx. corniger, Cx. quinquefasciatus and Li. durhami. PMID- 2883556 TI - Lack of effect of somatostatin on epinephrine-stimulated glucose production in the dog. AB - The effects of somatostatin on epinephrine-stimulated hepatic glucose production were assessed in the conscious overnight fasted dog. Glucose production was measured using a primed constant infusion of 3-3H-glucose. Two experiments were performed on each of four animals, each experiment consisting of a tracer equilibration period (80 minutes), a control period (40 minutes), and a test period (180 minutes). In the first experiment, epinephrine was infused at 0.08 microgram/kg/min during the test period so that the plasma concentration rose from 138 +/- 4 to 727 +/- 109 pg/mL. In the second experiment two weeks later, epinephrine was again infused (112 +/- 17 to 727 +/- 148 pg/mL) but with somatostatin (0.8 microgram/kg/min) and intraportal replacement amounts of insulin and glucagon. The pancreatic hormones were administered in such a way as to mimic the insulin and glucagon levels observed during epinephrine infusion in the first experiment. In the first experiment, epinephrine caused changes in insulin and glucagon levels at five minutes of plus 9 +/- 1 microU/mL and minus 1 +/- 3 pg/mL, respectively, and averaged plus 6 +/- 2 microU/mL and minus 9 +/- 5 pg/mL over the first hour. Glucose production peaked at 15 minutes (increment of 0.83 +/- 0.24 mg/kg/min) and increased by an average of 0.38 +/- 0.12 mg/kg/min in the first hour. In the second experiment, intraportal replacement of insulin and glucagon during epinephrine infusion resulted in changes in insulin and glucagon levels at five minutes of plus 8 +/- 3 microU/mL and plus 2 +/- 2 pg/mL, respectively, and averaged plus 4 +/- 2 microU/mL and minus 7 +/- 6 pg/mL over the first hour.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883557 TI - Effects of delipidation on proton translocation and ATPase activity in beef heart electron transport particles. AB - Delipidation of beef heart electron transport particles with phospholipase A2 has been examined. When the particles were treated with the lipase and subjected to a low bovine serum albumin wash, ATPase activity was unaffected as was the lipid/protein ratio of the particles. However, energisation by ATP/Mg2+ was abolished. Furthermore, unsaturated but not saturated fatty acids discharged the steady-state ATP-driven membrane potential of control samples. When the phospholipase A2 hydrolysis products were removed, inhibition of energy-linked reactions in the lipid-depleted particles was still observed and was interpreted in terms of non-specific leaks in the vesicle membranes, and 'specific' leaks through impaired H+-ATPase complexes. ATPase activity was less susceptible to delipidation than energisation but was, nevertheless, strongly inhibited at 50 percent lipid depletion. Spin label studies indicated a decrease in the fluidity of particle membranes accompanying delipidation. Moreover, the discontinuity seen in Arrhenius plots of ATPase activity was shifted from 17 degrees C (control) to 22 degrees C at 50 percent phospholipid depletion. The data are consistent with a release of unsaturated fatty acids by phospholipase A2 rendering the transport particles both leakier and the membranes less fluid than controls. PMID- 2883558 TI - Surface properties of Escherichia coli strains responsible for urinary infections. AB - Many studies shown that the capacity of the bacteria to adhere to the host cells is a fundamental requisite to the onset of any colonization process and hence infection. Our results shown that E. coli strains from patients with recurring urinary tract infections showed a high degree of surface hydrophobicity, correlated with the presence of numerous fimbriae with respect to a control group. PMID- 2883559 TI - Correlation between growth rate and loss of histamine-sensitizing factor during antigenic modulation in Bordetella pertussis. AB - The pattern of loss of histamine-sensitizing factor (HSF) during antigenic modulation of Bordetella pertussis in Hornibrook medium was examined. The aim was to determine the possible underlying mechanism involved in modulation. Normal (X mode) B. pertussis cells were grown in Hornibrook medium in which 0.5% (w/v) NaCl had been replaced with 0.5% (w/v) MgSO4. 7H2O (C-medium). At various time intervals during growth, the viable cell numbers and optical densities of both cultures in the X- and C-media were estimated. Whole cells were harvested from the cultures at the same time intervals and aliquots from the cultures were assayed for the levels of their histamine-sensitizing properties. Correlation of the increase in viable cell numbers with rate of loss of histamine-sensitizing activity in both the cells and whole cultures indicated that components responsible for the histamine-sensitizing activity were not synthesized during modulation. Moreover, the loss of HSF from B. pertussis cells was faster than can be explained by dilution of the original factor in the inoculum among progeny cells. Modulation may involve cessation of synthesis and selective degradation or denaturation of some envelope polypeptides immediately upon inoculation of normal X-mode B. pertussis cells into C-medium. PMID- 2883560 TI - Guanfacine for hypertension. PMID- 2883561 TI - [Combined infections in the pathology of larvae of blood-sucking mosquitoes. 1. Entomopathogenic qualities of bacterial complexes]. PMID- 2883562 TI - [Larvicidal activity of a Bacillus thuringiensis H-l4, strain BTS-393, preparation kept in long-term storage]. PMID- 2883563 TI - [Discovery in the territory of the USSR of Entomophthora aquatica Anderson et Ringo pathogenic to mosquitoes]. PMID- 2883565 TI - [Prospects of improving microbial larvicides and methods of control of blood sucking insects and disease vectors]. PMID- 2883564 TI - [Species composition and density of blood-sucking mosquitoes (Diptera, Culicidae) infesting the suburbs of Ustinov in the Udmurt ASSR]. PMID- 2883566 TI - [Blood-sucking mosquitoes in the area of the pioneer camp Druzhba in the Udmurt ASSR]. PMID- 2883567 TI - Structure-activity relationships of beta-adrenergic receptor-coupled adenylate cyclase: implications of a redox mechanism for the action of agonists at beta adrenergic receptors. AB - The present studies have tested the hypothesis that agonists at beta-adrenergic receptors activate the beta-receptors by reducing them. This was examined by analyzing the interactions of 41 beta-agonists and antagonists with the receptors. The structural features which determined binding affinity (KD) were shown to be distinct from those which determined intrinsic, activity (IA). The IA was shown to be related to the oxidation-reduction properties which were determined primarily by the nature of the substituents on the phenyl ring. Thus, the parent compound phenylethanolamine, having no phenolic substituent, acted as an antagonist (IA = 0) and was also redox inactive. All of the antagonists tested (19) exhibited EP (peak potential for the first oxidative wave) values greater than 0.75 V, suggesting that they were difficult to oxidize. Agonists, however, exhibited a wide range of EP (0.25-0.7 V) with values lower than those of the antagonists. The agonists tested include catecholamines, catecholamine analogs bearing meta-substituted amino functionalities (such as amino, methylamino, formanilide, sulfonamide, urea, and carbamate), resorcinol, and hydroxymethyl congeners. It is proposed that the oxidizing tendency of the substituent on the phenyl ring is one of the factors that influences IA. To test the hypothesis further, we electrolytically oxidized isoproterenol to adrenochrome or to the o quinone intermediate and tested for activity. The 4e-, 4H+-oxidation product adrenochrome did not bind to or stimulate adenylate cyclase, suggesting that the reducing ability to isoproterenol is important for its agonistic activity. A cyclic redox mechanism for the action of agonists at beta-adrenergic receptors is presented. We propose that agonist are electron donors. Their interactions with receptors result in reduction leading to activation of the receptors. PMID- 2883568 TI - On the structure-activity relationship of histamine H2-receptor antagonists based on the X-ray crystal structures and 1H-NMR spectra of amidine derivatives. AB - The conformation of six amidine compounds, which possess a common 3-[(4 thiazolyl)methylthio]propionylamidine framework but exhibit different activities as histamine H2-receptor antagonists, have been subjected to both single crystal X-ray structural and 1H-NMR analyses. The X-ray studies suggest a correlation between antagonist activity and the relative spatial orientation of the thiazolyl and amidine nitrogen atoms. This correlation is supported by a comparison of the conformations observed for the amidines with those of other H2-receptor antagonists and reveal that a folded conformation, specifically the NH...N intramolecular hydrogen-bonded configuration, is important for antagonist activity. The 1H-NMR measurements on the active amidine compounds show that the intramolecular NH...N bond is likely to be present in solution. PMID- 2883569 TI - The transport of S-cysteine conjugates in LLC-PK1 cells and its role in toxicity. AB - The transport of S-cysteine conjugates was studied in the kidney cell line, LLC PK1, using the nephrotoxin, S-(1,2-dichlorovinyl)-L-cysteine (L-DCVC), as the model compound. The saturable uptake of this conjugate did not require sodium and was selectively inhibited by the amino acid transport system L-specific substrate, 2-amino-2-norbornane carboxylic acid, as well as a variety of other S cysteine conjugates and neutral amino acids with large, nonpolar side chains. Kinetic studies suggested the existence of both low and high affinity transport systems with Km values that differed by 25-fold. Although these uptake systems showed no discernible differences in substrate specificity, the low affinity transport was more sensitive to trans-stimulation. L-DCVC uptake in subconfluent cultures was about 3-fold that of confluent cells, suggesting either adaptive regulation to cell growth or polarization of transport to the basolateral membrane. L-DCVC toxicity in LLC-PK1 cells was inhibited in the presence of nontoxic transport substrates but was potentiated when cells were preloaded with many of the same compounds, indicating that transport may be a rate-limiting factor in L-DCVC-induced toxicity under certain circumstances. The possible role of this system L-like uptake in the transport of S-cysteine conjugates in vivo is discussed. PMID- 2883570 TI - Alteration of intracellular cAMP levels and beating rates of cultured chick cardiac cells by Bordetella pertussis adenylate cyclase. AB - Bordetella pertussis, the pathogen responsible for whooping cough, releases a soluble calmodulin-sensitive adenylate cyclase into its culture medium which enters several different types of animal cells and elevates intracellular cAMP. In this study, the influence of B. pertussis adenylate cyclase on intracellular cAMP levels of cultured chick cardiac cells and the beating rates of chick cardiac cell aggregates was examined. Treatment with B. pertussis adenylate cyclase caused up to a 60-fold increase in intracellular cAMP which was significantly greater than that caused by forskolin or isoproterenol. Increases in intracellular cAMP caused by B. pertussis adenylate cyclase were observed within 2 min after treating cells with the enzyme, and binding of calmodulin to the enzyme inhibited these effects. In addition, high concentrations of the enzyme completely inhibited the beating of cardiac cells. However, lower concentrations of the adenylate cyclase accelerated beating rates 30-40% and cardiac cells continued to beat at an accelerated rate for at least 30 min. These data indicate that B. pertussis adenylate cyclase invades chick cardiac cells and catalyzes significant increases in intracellular cAMP. It is proposed that the effect of the enzyme on the beating rates of heart cell aggregates may be due to alteration of intracellular cAMP levels. PMID- 2883573 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 18-1987. A 31-year-old asthmatic woman with rapidly progressive multisystem disease. PMID- 2883571 TI - Characterisation of the structure and expression of the gene encoding a major female specific polypeptide of Schistosoma mansoni. AB - A previously described cDNA clone, pSF10, of Schistosoma mansoni encoding the very dominant female specific polypeptide (FSP) has been used to characterize the gene and its expression. The gene is detectable in different isolates of S. mansoni and is estimated to be present in 3 copies per haploid genome. The gene is not sex linked and exhibits neither amplification nor rearrangement concomitant with expression. Expression of the gene by parasites maturing in hamsters is first detected after 5 weeks when the RNA is present at 1/10 the level of that of 6 week worms. Although the FSP gene is specifically and highly expressed by egg laying female worms a corresponding polypeptide produced by the cell-free translation of RNA is not detectable. It was confirmed, however, that pSF10 does indeed encode a mRNA by DNA sequence analysis. The sequence demonstrated a mRNA containing a poly(A) tail and two open reading frames. One reading contains no methionine but is very high (47%) in glycine. This amino acid composition could account for the inability to detect the gene product by cell free translation in the presence of [35S]methionine. PMID- 2883572 TI - Localization and identification of an Entamoeba histolytica adhesin. AB - The adherence of Entamoeba histolytica trophozoites to target cells was studied by using monoclonal antibodies (MAbs) and adhesion-deficient mutants of the parasite. MAbs Adh-1 and Adh-2 reacted with a surface protein of approximately 112 kDa of the total proteins of trophozoites from the wild type strain, clone A, strain HM1:IMSS. Both MAbs reacted weakly with the adhesion-deficient mutant clones, C-98, C-919 and C-923, all derived from HM1:IMSS. MAbs Adh-1 and Adh-2 incubated with trophozoites from clone A inhibited adherence to red blood cells, erythrophagocytosis and cytopathic effect on cell culture monolayers. Antibodies against a approximately 112 kDa polypeptide were found in the sera from patients with hepatic abscess. These results demonstrate that the adherence of trophozoites to target cells is a necessary event in order for cytopathogenicity to occur. PMID- 2883574 TI - Infection with HTLV-I and HTLV-III in T8 lymphoproliferative disease. PMID- 2883575 TI - Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). AB - To evaluate the influence of the angiotensin-converting-enzyme inhibitor enalapril (2.5 to 40 mg per day) on the prognosis of severe congestive heart failure (New York Heart Association [NYHA] functional class IV), we randomly assigned 253 patients in a double-blind study to receive either placebo (n = 126) or enalapril (n = 127). Conventional treatment for heart failure, including the use of other vasodilators, was continued in both groups. Follow-up averaged 188 days (range, 1 day to 20 months). The crude mortality at the end of six months (primary end point) was 26 percent in the enalapril group and 44 percent in the placebo group--a reduction of 40 percent (P = 0.002). Mortality was reduced by 31 percent at one year (P = 0.001). By the end of the study, there had been 68 deaths in the placebo group and 50 in the enalapril group--a reduction of 27 percent (P = 0.003). The entire reduction in total mortality was found to be among patients with progressive heart failure (a reduction of 50 percent), whereas no difference was seen in the incidence of sudden cardiac death. A significant improvement in NYHA classification was observed in the enalapril group, together with a reduction in heart size and a reduced requirement for other medication for heart failure. The overall withdrawal rate was similar in both groups, but hypotension requiring withdrawal occurred in seven patients in the enalapril group and in no patients in the placebo group. After the initial dose of enalapril was reduced to 2.5 mg daily in high-risk patients, this side effect was less frequent. We conclude that the addition of enalapril to conventional therapy in patients with severe congestive heart failure can reduce mortality and improve symptoms. The beneficial effect on mortality is due to a reduction in death from the progression of heart failure. PMID- 2883576 TI - Polymorphic gene marker studies. PMID- 2883577 TI - Development of DNA probes to investigate genetic variation of alcohol metabolizing enzymes. PMID- 2883578 TI - Of how great significance? PMID- 2883579 TI - CD4+ murine T cells develop from CD8+ precursors in vivo. AB - The adult murine thymus contains four subpopulations of thymocytes defined by the T-cell surface antigens CD4 (L3T4) (a marker of helper T cells) and CD8 (Lyt2) (a marker of cytotoxic/suppressor T cells): CD4+8- and CD4-8+ (single positives), CD4+8+ (double positives) and CD4-8- (double negatives). To understand how T cells develop in the thymus, it is important to determine the lineage relationships among these subpopulations. In particular, the status of double positives, which make up approximately 80% of the total thymocyte population, has long been controversial. Some purpose that double positives are 'dead-end cells' that all die in the thymus, perhaps because they have been rejected by some selection process. Others suggest that, although most double positives die in the thymus, some develop into the more mature single positives that leave the thymus. The experiments presented here show that repeated injections of anti-CD8 monoclonal antibodies block the development of CD4+ cells, demonstrating that these cells develop from CD8+ precursors, probably double positive thymocytes, in vivo. PMID- 2883580 TI - Cystic fibrosis. Classical and reverse genetics. PMID- 2883581 TI - A candidate for the cystic fibrosis locus isolated by selection for methylation free islands. AB - A genomic sequence close to the cystic fibrosis locus with the characteristics of an HTF island has been selectively cloned and characterized. Two markers flanking this sequence, which is conserved throughout mammalian evolution, show a very much greater disequilibrium than that found with any existing marker. A single mutational event accounts for most cases of cystic fibrosis. The sequence is expressed, and is a candidate for the cystic fibrosis gene. PMID- 2883582 TI - Insect evolution. Molecules and morphology. PMID- 2883583 TI - Differential effects of various secretagogues on quantal transmitter release from mouse motor nerve terminals treated with botulinum A and tetanus toxin. AB - Electrophysiological and electron microscopic techniques were used to investigate the actions of potassium depolarization, black widow venom (BWSV), Ca2+-ionophore A 23187 and hyperosmotic solution on mouse hemidiaphragms poisoned in vitro with botulinum A toxin (BoTx) and tetanus toxin (TeTx). These neurotoxins reduced the frequency of miniature endplate potentials (m.e.p.ps) from 5/s of the control to 2/min and 21/min, respectively. High potassium (25 mmol/l) increased the m.e.p.p. frequency at BoTx- and TeTx-poisoned endplates to 30/min and 50/s, respectively. The ultrastructure of endplates showed no obvious changes. BWSV (0.04 glands/ml) was just as effective in promoting transmitter release from BoTx-treated endplates as in control preparations. Electron micrographs revealed depletion of vesicles as well as swollen and disrupted mitochondria. When preparations were pretreated with TeTx, BWSV only moderately increased transmitter release and no alterations of the ultrastructure could be observed. At TeTx- or BoTx-poisoned endplates Ca2+-ionophore A 23187 usually produced an extreme reduction of m.e.p.p.-frequency (0.005/s), sometimes preceded by a short burst-like release. The ultrastructure of these endplates was not obviously affected. Application of hyperosmotic solution to BoTx- or TeTx-poisoned preparations further reduced the already low m.e.p.p.-frequency. These results further demonstrate that TeTx and BoTx act at different sites in the transmitter releasing process. PMID- 2883584 TI - B-HT 920 and B-HT 958: presynaptic effects on electrically evoked 3H-dopamine release from slices of rat nucleus accumbens. AB - The effects of two thiazoloazepine derivatives, B-HT 920 (6-allyl-2-amino-5,6,7,8 tetrahydro-4H-thiazolo[4,5-d]azepine) and B-HT 958 (2-amino-6-(p-chloro-benzyl) 4H-5,6,7,8-tetrahydrothiazolo[5,4-d]a zepine) on electrically evoked overflow of 3H-dopamine were studied. Slices from nucleus accumbens of the rat were preincubated with 3H-dopamine and superfused at 23 degrees C or 37 degrees C. Electrical field stimulation was applied using frequencies of 0.5 or 5 Hz. At 37 degrees C/5 Hz, B-HT 920 markedly and dose-dependently (0.01-0.1 mumol/l) reduced the stimulation evoked overflow of tritium. Its dose-response curve was shifted to the right at 23 degrees C/0.5 Hz and 23 degrees C/5 Hz, respectively. A similar result was obtained with the dopamine receptor agonist, apomorphine (1 mumol/l). B-HT 958 (0.1-10 mumol/l) also reduced electrically induced overflow of tritium at 37 degrees C/5 Hz, had no effect at 23 degrees C/0.5 Hz, and facilitated tritium overflow at 23 degrees C/5 Hz. Sulpiride (10 mumol/l) completely prevented the effects of B-HT 920 (1 mumol/l) or B-HT 958 (1 mumol/l) at 37 degrees C/5 Hz, whereas phentolamine (1 mumol/l) had no effect on the actions of the two drugs under these experimental conditions. From the patterns of effects obtained under the different experimental conditions it is concluded that B-HT 920 acts as full agonist at presynaptic dopamine autoreceptors whereas B-HT 958 acts as partial agonist. PMID- 2883586 TI - [Prune-belly syndrome: experiences with 9 patients]. PMID- 2883587 TI - [Narcotic analgesics with attention to special routes of administration]. PMID- 2883585 TI - Pharmacological characterization of the postsynaptic alpha-adrenoceptors in isolated canine mesenteric arteries and veins. AB - This investigation was undertaken to characterize the postsynaptic alpha adrenoceptors in isolated canine mesenteric arterial and venous preparations. Contractile responses to cumulative additions of phenylephrine (selective alpha 1 adrenoceptor agonist), UK-14,304 (selective alpha 2-adrenoceptor agonist), noradrenaline (non-selective alpha-adrenoceptor agonist), and dopamine (non selective alpha-adrenoceptor agonist) were measured in the presence and absence of rauwolscine, a selective alpha 2-antagonist, and terazosin, a selective alpha 1-antagonist. Phenylephrine was a more potent agonist in the mesenteric artery than in the mesenteric vein; UK-14,304 exhibited the opposite profile of activity. Terazosin was a more potent antagonist than rauwolscine against each of the agonists, except dopamine, in the mesenteric artery but rauwolscine was more potent than terazosin in the vein. Terazosin and rauwolscine were equipotent in inhibiting the contractile responses to dopamine in the artery while rauwolscine was more potent than terazosin in the vein. The pA2 values measured in both vessels failed, however, to demonstrate a high selectivity for either alpha adrenoceptor antagonist. These results suggest that the alpha-adrenoceptors in the canine mesenteric artery and vein exhibit pharmacological characteristic typical of both alpha 1- and alpha 2-adrenoceptor subtypes. PMID- 2883588 TI - [Effects of aspartic acid in the electroreceptors of the skate]. AB - To identify the afferent transmitter in ampullary electroreceptors of the marine skates effects of L-aspartic acid (L-ASP) were examined using bath application of the drug. Perfusion of the basal membrane with L-ASP produced an increase in activity in most experiments (threshold concentrations 10(-7) M). L-GLU and L-ASP were identical in their ability to activate the afferents. In the presence of presynaptic blockade (high Mg2+) bath application of L-ASP restored the resting activity, suggesting a postsynaptic action of L-ASP. The results are consistent with the view that L-GLU, L-ASP or a related compound may play a role in afferent transmission in the ampullae of Lorenzini of skates. PMID- 2883589 TI - Effects of branched chain amino acids, pyruvate, or ketone bodies on the free amino acid pool and release from brain cortex slices of normal and streptozotocin diabetic rats. AB - Brain cortex slices from diabetic rats incubated in Krebs-Ringer-bicarbonate (KRB)--glucose medium show, compared to the normals, a 75% higher glutamine content. Branched chain amino acids (BCAA) added, at 0.5mM each, to this medium increase (53%) the glutamine content in the normal slices but have no effect on the glutamine content in the slices from diabetic rats. When the incubation medium is KRB-pyruvate, glutamine and glutamate contents are lower than in the KRB-glucose medium. The addition of BCAA in the KRB-pyruvate medium partially restores the contents of glutamine in the normal and of glutamine plus glutamate in the diabetic. Keto acids or BCAA added to the incubation medium of normal slices decrease the pool of most of the neutral and acidic amino acids but they do not affect this pool in slices from the diabetic rats. In addition keto acids increase the ratio glutamate in the tissue: glutamate in the medium. PMID- 2883590 TI - Neurotransmitter enzyme activities in neurons purified by bulk-isolation. AB - Neurons, purified by bulk-isolation procedures from 10 day-old rat brain, are 80 90% homogeneous. Contaminants are primarily blood vessels and occasional oligodendroglia. All sizes and shapes of neurons are obtained, as they are isolated from all areas of the brain, except the cerebellum. Neurotransmitter enzyme activities involved in the metabolism of catecholamines, acetylcholine, and GABA are found at twice the level in these purified neurons when compared to that found in whole brain tissue. However, acetycholinesterase is found at a similar activity as in whole brain tissue, suggesting its localization in other cell types as well. Thus purified rat neurons are a good model system for studying neuronal function. PMID- 2883591 TI - Contributions of basic neurochemistry towards a novel concept of epilepsy. AB - Epilepsy is an ancient disorder which treatment over the centuries has been guided by preconceptions regarding its origin. The major improvements in epilepsy management came following the discovery of the EEG and the development of seizure suppressing agents. These advances in diagnosis and anticonvulsant therapy have further ingrained the conviction that epilepsy is a disease of neurons. Evidence presented here is intended to support a different point of view which suggests that the metabolic modifications in epileptogenic tissue denote subtle alterations in the anatomical and biochemical relationship between neurons and their glial envelopes. As a result the extracellular environment of these cells contain higher than normal levels of glutamic acid. This creates an unnatural functional connectivity between neurons so that they establish abnormal synchronous activity between them and become hyperexcitable due to the depolarizing milieu. To compensate for these biochemical changes it is suggested that some thought might be given to epilepsy management by metabolic manipulation. The measures should be directed specifically towards improving the ability of glia to remove glutamic acid from the extracellular milieu. Two obvious possibilities are to enhance glial glutamine synthesis and to improve the interstitial "wash-out" of glutamic acid in epileptogenic epicenters. Such a therapy would anticipate to gradually diminish seizure incidence and susceptibility without, however, having a direct action on convulsive episodes per se. The approach must be considered an adjunct to current epilepsy treatment and not a substitute for the use of anticonvulsants. PMID- 2883592 TI - Cholinergic function in the nineties: advantages of work with a model system. PMID- 2883593 TI - Uptake and release for glutamine and glutamate in a crude synaptosomal fraction from rat brain. AB - [14C]Glutamine uptake in a crude synaptosomal (P2) fraction, (representing the sum of [14C]glutamine accumulated and [14C]glutamate formed by hydrolysis), is distinct from glutamate uptake. Glutamine uptake is Na+-independent and unaffected by the Na+-K+-ATPase inhibitor ouabain, whereas glutamate uptake is Na+-dependent and inhibited by ouabain. The uptake of both glutamine and glutamate is unaffected by the gamma-glutamyltransferase inhibitor, Acivicin. This indicates that glutamine uptake is not mediated by a carrier, as distinct from that of glutamate, and also not linked to gamma-glutamyl-transferase. Na+ affects the distribution of glutamine-derived glutamate by increasing the synaptosomal content and reducing that of the medium. When glutamate release from synaptosomes preloaded with [14C]glutamate is measured by superfusion technique in order to prevent reuptake, Na+ has been found to inhibit release in a non depolarizing medium (Ringer buffer with no Ca2+) of the [14C]glutamate as well as of endogenous glutamate. The specific activity of the [14C]glutamine-derived glutamate in the incubation medium is much higher than that in the synaptosomes, indicating that there exists a readily releasable pool of newly formed glutamate in addition to another pool. The latter glutamate pool is partially reduced by Na+. PMID- 2883595 TI - Effect of continuous somatostatin and growth hormone-releasing hormone (GHRH) infusions on the subsequent growth hormone (GH) response to GHRH. Evidence for somatotroph desensitization independent of GH pool depletion. AB - Continuous infusions of growth hormone-releasing hormone (GHRH) attenuate the subsequent growth hormone (GH) response to GHRH. To test whether this phenomenon can occur in the absence of GH pool depletion, we examined the effects of continuous infusions of 10 nM GHRH and of 10 nM somatostatin (SRIH), separately or in combination, on dispersed, perifused rat anterior pituitary cells. Columns of these cells were given either GHRH alone for 5 h, GHRH and SRIH together for 3 h followed by GHRH alone, or SRIH alone for 3 h followed by GHRH or medium. SRIH blunted both basal GH release and the GH response to GHRH, without affecting the subsequent GH responses to GHRH. The GHRH infusions attenuated the subsequent GH response to GHRH, even when GH release was initially prevented by the concurrent infusion of SRIH. Furthermore, the degree of attenuation was similar in the presence or absence of SRIH, suggesting that pool depletion plays little role in the desensitization process under these experimental conditions. The results are consistent with the hypothesis that a short-term infusion of GHRH leads to attenuation of the GH response in rat anterior pituitary cells primarily through receptor effects rather than through GH pool depletion. PMID- 2883594 TI - Translational regulation in rat brain hemispheres. AB - Present studies on the sensitivity of the transcription process in rat cerebral hemispheres showed that the relative abundance and translation of free and bound poly (A)+ mRNAs in a reticulocyte mRNA-dependent system were reduced following 1 h and 4 h of ethanol or pentobarbital administration with free being affected to a greater extent than the bound poly (A)+ mRNAs. In addition, the energy dependent nucleocytoplasmic transport of in vivo [3H]labeled nuclear RNA to surrogate cytoplasm was modified in response to ethanol exposure. The translocation of the labeled nuclear RNA fraction occurred only to the microsomal/ribosomal fractions of the cytoplasm, was stimulated by cyclic cAMP and abolished when the cytoplasm was depleted of its protein factors following streptomycin treatment, thereby establishing the translocated RNA as messenger RNA. It is concluded that the neural cell, in response to ethanol exposure, modifies the efficiency of nuclear processing and transport of mRNA. This nuclear restriction probably occurs at multi-levels during the post-transcriptional modification of mRNAs. PMID- 2883596 TI - Immunostaining reveals accumulation of serotonin and coexistence with tyrosine hydroxylase in hypothalamic neurons of acutely stalk-sectioned baboons. AB - The distribution of serotonin (5-HT) and tyrosine hydroxylase (TH) was examined in the hypothalamus of juvenile baboons, 24 h after infundibular stalk section. Simultaneous immunostaining for 5-HT with peroxidase-antiperoxidase (PAP) and TH with 15 nm colloidal gold (IGS) was performed on Vibratome sections from 3 operated and 1 control female. Light microscopy revealed fine 5-HT immunopositive (5-HT+) fibers, presumably axons, in the suprachiasmatic nuclei and ventromedial hypothalamus (VMH) after stalk section. In addition, focal accumulations of swollen and heavily stained 5-HT+ fibers occurred on the side of the surgical approach. Enlarged fibers were densest in the medial preoptic area, lateral and VMH areas, and the median eminence. TH immunoreactivity (TH+) in VMH cell bodies and axons was only slightly increased over that in controls. Electron microscopy of areas of 5-HT+ and TH+ overlap (medial VMH and adjacent periventricular zone) showed that 5-HT+ profiles were mostly unmyelinated axons and irregular varicosities. A few myelinated 5-HT+ axons were also observed. TH+ perikarya, dendrites, axons and terminals showed gold labeling characteristic for this enzyme. However, colocalization of 5-HT (PAP) and TH (IGS) was present in a number of fiber varicosities in experimental animals only. Both single- and double-labeled profiles occurred in individual thin sections, thus arguing against antibody cross-reactivity. These results indicate that: hypothalamic 5 HT+ fibers project to the median eminence in primates; 5-HT fibers become more obvious after stalk section due to accumulation of transmitter; focal 5-HT+ immunoreactivity in the hypothalamus can increase dramatically after distant and mild surgical trauma, and coexistence of 5-HT and TH in single neurons can appear after acute stalk section and/or trauma in experimental animals. These findings might represent uptake of exogenous 5-HT or amplified expression of endogenous neurotransmitter, suggesting that plasticity of transmitter phenotype might follow acute surgical and/or endocrine intervention in mature primate brain. Neuroendocrine studies employing the stalk-sectioned primate might thus be radically affected. PMID- 2883597 TI - Consequence of dynorphin-A administration on anterior pituitary hormone concentrations in the adult male rhesus monkey. AB - This study examines the role of dynorphin-A(1-13) and dynorphin-A(1-10)-amide in the neuroendocrine regulation of anterior pituitary hormones in nonrestrained, adult male rhesus monkeys. The effects of these opioids on plasma concentrations of prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin (TSH) and growth hormone (GH) were assessed. Intravenous administration of dynorphin-A(1-13), 1-120 micrograms/kg, significantly increased plasma PRL levels. Average maximal increases of 90-230% occurred within 5 min and levels remained significantly elevated for up to 120 min. PRL response reached a plateau following the 30 micrograms/kg dose. Dynorphin-A(1-13) had no observable effects on plasma concentrations of LH, FSH, TSH or GH at any dose level studied. Administration of dynorphin-A(1-10)-amide produced significant dose-dependent increases in plasma PRL concentrations. Dose levels of 1-120 micrograms/kg produced mean peak increases from 100 to 230%, 5-10 min postadministration. Dynorphin-A(1-10)-amide had no significant effect on plasma concentrations of LH, FSH, TSH or GH. The increases in plasma PRL concentrations induced by dynorphin-A were naloxone-reversible. These results indicate a selective effect of dynorphin A on the regulatory mechanisms of PRL secretion over that of other anterior pituitary hormones. PMID- 2883598 TI - A model for combined morphological and functional investigations on the isolated mediobasal rat hypothalamus. AB - We have developed a model for combined morphological and functional in vitro studies of the isolated mediobasal hypothalamus (MBH) by considering two prerequisites: (1) the tissue must be well preserved, free of morphological artefacts and functionally unimpaired until the end of the in vitro incubation, and (2) the tissue must be processed for morphology in optimal conditions. To test our model we have studied some aspects of the luteinizing hormone-releasing hormone (LHRH) system in 4-month-old male Sprague-Dawley rats. After decapitation the MBH was isolated and put in a flask containing 0.5 ml Hepes-buffered Locke's medium gassed by 5 ml/min of O2/CO2 (95%/5%) and shaken in a water bath at 37 degrees C. After a 10-min washing, the medium was changed twice at an interval of 20 min. After the in vitro incubation the tissue was satisfactorily preserved as judged by light- and electron-microscopic analysis. LHRH, somatostatin and thyrotropin-releasing hormone could be demonstrated by alkaline phosphatase or peroxidase-antiperoxidase immunohistochemistry on semithin sections and by immunogold technique on thin sections. The LHRH secretion was close to basal values after 30 min of incubation (22.1 +/- 4.8 pg/MBH) and then remained constant for another period of 20 min (17.6 +/- 2.6 pg/MBH). During the second 20 min of incubation LHRH secretion increased in presence of 61.6 mM K+ (110.7 +/- 8.7 pg/MBH). Thus the isolated hypothalamus was excitable until the end of the in vitro incubation. We conclude that this model can be successfully used for combined morphological and functional studies. PMID- 2883599 TI - Intracerebroventricular infusion of a cyclic hexapeptide analogue of somatostatin inhibits hemorrhage-induced ACTH release. AB - This study examines the effect of intracerebroventricular infusion of the 'superactive' somatostatin (SRIF) analogue cycl--(N-Me-Ala-Tyr-D-Trp-Lys-Val-Phe) on the plasma adrenocorticotrophic hormone (ACTH) response to hemorrhage in conscious sheep. Hemorrhage (15 ml/kg over 15 min) increased plasma ACTH from 55 +/- 20 to 815 +/- 148 pg/ml at 30 min (p less than 0.001). Infusion of the SRIF analogue intracerebroventricularly at 0.08 microgram/min for 10 min prior to and for 60 min after commencement of hemorrhage resulted in a partial inhibition of the plasma ACTH response. Infusion of the analogue at 0.8 microgram/min blocked the increase in plasma ACTH at 30 min. Plasma ACTH was 21 +/- 3 pg/ml as control and 66 +/- 47 pg/ml at 30 min. The SRIF analogue had no effect on plasma ACTH in the same animals in control experiments with no hemorrhage. These studies suggest that SRIF may act as a central inhibitor of ACTH release. The mechanism by which the SRIF analogue inhibits ACTH secretion is unknown but could involve inhibition of corticotropin-releasing factor release and/or an inhibition of ACTH release from the pituitary gland. The route of administration of the SRIF analogue and the finding that the SRIF analogue did not prevent systemic corticotropin releasing factor stimulation of ACTH suggest an effect of the SRIF analogue in the hypothalamus. PMID- 2883600 TI - Evaluation of the regional cerebral vasodilatory capacity before carotid endarterectomy by the acetazolamide test. AB - To estimate the regional perfusion pressure and possibly the stump pressure during carotid endarterectomy, cerebral blood flow (CBF) measurements including a vasodilatory test were performed preoperatively. CBF was measured by 133Xe inhalation and emission tomography. An intravenous dose of 1g acetazolamide (Diamox) was used as cerebral vasodilator. Thirty-six patients with a clinical history of previous strokes (9 cases) or transient ischaemic attacks (27 cases) were studied. Nine of the patients showed occlusion of the contralateral internal carotid artery (ICA). The percent flow increase induced by Diamox in the ipsilateral hemisphere correlated to the ICA pressure was measured before clamping (n = 32, r = 0.55, p less than 0.001). In 12 of the 36 patients, Diamox caused a significant change in the flow distribution indicating a restricted regional vasodilatory capacity and a reduced regional perfusion pressure. In addition, these 12 patients showed a low stump pressure (less than 50 mmHg). However, 8 additional patients had uniform CBF increases at the Diamox test, but showed low stump pressures. It is concluded, that preoperative tests of the cerebral vasodilational capacity can be used to identify most patients with a low ICA pressure, and a substantial fraction of patients that will develop a low stump pressure upon ICA clamping during operation. In these patients with abnormal Diamox tests surgical reconstruction is particularly indicated, but, at the same time the perioperative risks are presumably highest in this group. PMID- 2883601 TI - Percutaneous subdural tapping for the treatment of chronic subdural haematoma in adults. AB - Chronic subdural haematoma in adults has been treated by percutaneous subdural tapping using a subdural needle. In order to prevent recurrence, the procedure including replacement of the haematoma with oxygen, irrigation using relatively small amounts of saline, and additional drainage for one hour proved to be simple and reliable. The detailed technique is illustrated, and sequential computed tomography scans in six patients treated with this procedure are presented. PMID- 2883602 TI - rCBF in brain tumours as measured by xenon enhanced CT. AB - Heretofore, the rCBF of brain tumours has been measured by the 133Xe clearance method, but the resolving power of this method is limited and flow values measured by this method correlate poorly with the anatomical structure. On the other hand, our xenon-enhanced method has several advantages over the conventional isotope method and enables us to evaluate rCBF with a resolving power of 4 mm. With this method, we evaluated rCBF in 15 brain tumour cases and obtained the following results: Mean rCBF value of the tumour is a little lower than that of grey matter and higher than that of white matter with oedematous change. The xenon-enhanced method enables us to distinguish the demarcation between the tumour area and the surrounding oedematous area and offers useful information for determining the extent of resection in surgery. Mean lambda value of the tumour which is not obtainable in vivo by radionuclide scanning, was 1.02 +/- 0.06 for gliomas and 0.72 +/- 0.09 for metastatic tumours. PMID- 2883603 TI - Hydrocephalus following aneurysmal subarachnoid haemorrhage. AB - Ninety-four patients with hydrocephalus following subarachnoid haemorrhage were investigated. Fourteen of these patients had temporary ventricular drains inserted, 19 had drains that were later converted to ventricular-peritoneal shunts, and 61 patients had shunts only. All patients were analysed with respect to their grade on admission, the distribution of blood on CT scan, their Glasgow Coma Score, their intracranial pressure, and the presence or absence of vasospasm on angiography. Outcome was analysed by shunt procedure and time of shunt insertion. The higher the grade on admission, the more likely it was the patient would require a shunt. Fewer patients with a good outcome required shunting as compared to those whose outcome was poor. Patients having more subarachnoid blood on CT scan tended to present with a lower Glasgow Coma Score. The outcome of patients with intraventricular haemorrhage was not obviously influenced by the insertion of a ventriculostomy. Vasospasm was not more common in patients requiring a ventriculo-peritoneal shunt, nor did early shunting in patients with hydrocephalus affect the incidence of vasospasm. The majority of patients were either shunted in the first three days or after 30 days post-SAH. The outcome was better in those patients shunted at a later date. PMID- 2883604 TI - Origin of the initial negative potential (N15) recorded on the skull by superficial radial nerve stimulation in the cat. AB - The origin of the initial prominent negative potential with a latency of about 15 msec (N15), recorded on the skull by superficial radial nerve stimulation was studied in the cat, and the following results were obtained. In the direct recording from the cortex, SEPs were elicited from the SI and SII areas, as well as the lateral gyrus and anterior suprasylvian gyrus. Among various wave forms recognized in the SI area, diphasic positive-negative (P-N) potential obtained from the postero-lateral part was most distinct, representing the primary evoked potential. Responses recorded on the dura and those directly on the cortex showed similar wave patterns over many sites. Although different forms of evoked potentials were recorded extensively over the skull, the most prominent negative potential was elicited at the site corresponding to the postero-lateral part of the SI area. The latency of this potential was approximately in agreement with that of the negative component of the P-N potential recorded on the cortex. Based on the intracortical laminar analysis of P-N potential, the positive component of this potential was assumed to reflect the activity of cells in the deeper layer of the cortex. The negative component, on the other hand, might represent activities of apical dendrites of the cortex. From the result of functional elimination of the cortex, however, this positive component was thought to contain potentials from far field neural structures. N15 recorded on the skull completely disappeared during cortical spreading depression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883605 TI - Membrane phospholipid composition and membrane fluidity of human brain tumour: a spin label study. AB - Membrane fluidity in membrane phospholipids of brain tumours was investigated and compared with those of white and grey matter. Fifteen brain tumours including 5 gliomas, 5 meningiomas and 5 metastatic cancers were examined. These samples were frozen immediately after extirpation in liquid nitrogen. After extraction of total lipids from the tumour tissues, membrane phospholipids were separated and analysed by thin-layer and gas-liquid chromatography. The fluidity of the phospholipid membrane was studied by electron spin resonance (ESR) spectroscopy, using a stearate spin probe. The fatty acid composition of total phospholipid of brain tumours was characterized by an increase in linoleic and arachidonic acids when compared to the control brain. The percentage of palmitoleic acid was higher in gliomas and metastatic tumours than in meningiomas. Furthermore, in the brain tumour tissues, the decreases of phosphatidylethanolamine and phosphatidylserine and the increase of phosphatidylcholine were observed when compared with grey or white matter with the exception of meningioma. There was some difference in phospholipid membrane fluidity between brain tumour and control brain tissue. The order parameter calculated from ESR spectra became higher in the following order: metastatic brain tumour, less than meningioma, less than grey matter, less than glioma, less than white matter. These results suggest that the phospholipid metabolism in the brain tumour is different from that of the normal brain, and this difference may affect the alteration of membrane physical properties which exhibit in part the character of the transformation. PMID- 2883606 TI - Retrogasserian glycerol injection or percutaneous stimulation in the treatment of typical and atypical trigeminal pain. AB - Of 164 patients with trigeminal neuralgia treated by percutaneous retrogasserian glycerol injections, we have studied the long-term outcome (one to four years) of 72 patients. 51 patients suffered from idiopathic trigeminal neuralgia, and of these 92% were freed from pain by the operation. 21 patients suffered from symptomatic trigeminal neuralgia due to multiple sclerosis or of traumatic or infectious origin. Of these, only 38% became free of pain. A further 8 patients with facial deafferentation pain who underwent treatment by retrogasserian neurostimulation with a permanently implanted electrode were included in this study. 4 of these patients were rendered free of pain by this procedure. PMID- 2883607 TI - Pain management after lower extremity amputation. AB - Phantom pain may occur in up to 85% of patients after limb amputation. Although the pathophysiology of postamputation phantom pain is not well understood, it seems to be produced by a complex multifactorial interaction between the peripheral, sympathetic, and central nervous systems. The theoretical aspects of this are reviewed. Management of phantom limb pain may be both medical and surgical. Among the pharmacological agents proved effective against phantom pain are beta-blockers, tricyclic antidepressants, and anticonvulsants. Surgical management includes peripheral nerve stimulation, thermocontrolled coagulation of the spinal cord, spinal cord stimulation, transcutaneous nerve stimulation, and stereotactic deep brain stimulation. PMID- 2883608 TI - [Use of somatostatin in acute pancreatitis of biliary origin]. AB - The aetiology of acute pancreatitis may be alcoholic, dyslipidaemic, post operative, traumatic, cryptogenic or biliary and only the biliary form is considered here. Fifteen patients with biliary pancreatitis and blood amylase above 250 mg (n.v. less than 100) were encountered in 1984-85. Six patients were given traditional medical treatment and 9 somatostatin alone. Despite the limited number treated the results obtained in the second group appear to confirm the validity and efficacy of somatostatin. In fact given the rapid disappearance of pain and the normalisation of the altered blood parameters it was never necessary to administer somatostatin for more than 24-36 hours. PMID- 2883609 TI - Denervation supersensitivity of striatal D2 dopamine receptors is restricted to the ventro- and dorsolateral regions of the striatum. AB - The precise topographical changes in striatal D2 dopamine receptors that occur after neurotoxic lesion of the mesostriatal dopaminergic pathway have been studied autoradiographically in the rat through the use of [3H]spiperone as a ligand. 6-Hydroxydopamine-induced lesion of the dopaminergic afferents to the striatum caused an increase in [3H]spiperone binding in the ventro- and dorsolateral but not in the ventro- and dorsomedian aspects of the striatum. This lesion caused a loss of tyrosine hydroxylase-like immunoreactivity in all striatal subregions. These results demonstrate that not all striatal D2 dopamine receptors are able to proliferate after dopaminergic denervation. PMID- 2883610 TI - Chloride transport blockers inhibit the chloride-dependent glutamate binding to rat brain membranes. AB - The effects of a series of chloride transport blockers (ethacrynate, furosemide, torasemide, 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene and diphenylcarboxylate) on Cl(-)-dependent L-[3H]glutamate (Glu) binding were tested in rat brain membranes, Cl-transport blockers inhibit the Ca2+/Cl(-)-induced increase in L-[3H]Glu binding, some of them without affecting the Ca2+/Cl(-) independent L-[3H]Glu binding. Increasing the medium osmolarity by augmenting the sucrose concentration also inhibited the Ca2+/Cl(-)-induced increase in L-[3H]Glu binding. The effects of both sucrose and Cl-transport blockers were not additive, suggesting that they acted on the same type of mechanism. We recently suggested that L-[3H]Glu binding to brain membranes corresponds to Glu uptake in membrane vesicles. Therefore we propose that the Cl-transport blockers inhibit a Cl(-) dependent Glu accumulation into these vesicles. PMID- 2883612 TI - Offspring control of cerebrospinal fluid GABA concentrations in lactating rats. AB - The concentrations of gamma-aminobutyric acid (GABA) and its metabolic precursors glutamate (Glu) and ornithine (Orn) were measured in cerebrospinal fluid (CSF) samples obtained from the cisterna magna of freely moving lactating rats on: postpartum day 5 when the rats were with their pups, day 6, 6 h after removal of the pups, and day 7, 24 h after mother-pup reunion. The concentration of GABA was non-detectable in the absence of pups (condition 2) but forty-fold above the limit of detection whenever the rats and the pups were together (conditions 1 and 3). Glu and Orn were low in but increased in and still more so in. Thus, the CSF concentration of GABA, an inhibitory neurotransmitter which profoundly influences behavior and hormone secretion is markedly increased by the pup-related stimuli, which control the behavior and the endocrine secretions of the lactating rat. PMID- 2883611 TI - A population of Thy-1 molecules associated with the cytoskeleton. AB - Using a monoclonal antibody, SB1 38.456, raised against chicken neuronal Thy-1, we have shown that a significant amount of Thy-1 is associated with the non-ionic detergent-insoluble fraction of chicken brain membranes. Furthermore, this population of Thy-1 is not released by any biochemical method which disrupts microfilaments, microtubules or intermediate filaments, but is released by raising the temperature to 40 degrees C in high ionic strength, cation-containing buffer. We propose, therefore, that a population of Thy-1 molecules is associated with the cytoskeleton either via a linker protein or via other cell surface glycoproteins which are directly associated with the cytoskeleton. PMID- 2883613 TI - Biphasic effect of quinolinate on frog spinal, but not rat cortical, neurones: N methyl-D-aspartate-like depolarisation and a novel type of hyperpolarisation. AB - Using grease seal techniques on rat cerebral cortical slices and on frog hemisected spinal cords, bath applied N-methyl-D-aspartate (NMDA; 10-160 microM) and quinolinate (0.25-8 mM) induced dose-dependent depolarisations. These depolarising responses, but not those to quisqualate or kainate, were reduced by 2-amino-5-phosphono-valerate (2-AP5; 10-100 microM), magnesium (0.1-10 mM) and ketamine (10-100 microM). A novel dose-dependent hyperpolarising response to quinolinate (0.1-2 mM) but not to NMDA was observed only on frog motoneurones, and this was not reduced by classical amino acid receptor antagonists. PMID- 2883614 TI - Post-tetanic contractile events further support the interaction of multiple neurotransmitters in the neuroeffector junction of the rat vas deferens. AB - Post-tetanic events were recorded in isolated, superfused, epididymal and prostatic halves of the rat vas deferens. Increasing the frequency of nerve stimulation from 0.15 to 15 Hz (1-30 s) and then back to 0.15 Hz produced a post tetanic potentiation (PTP) of the muscular responses in the epididymal end but a post-tetanic inhibitory response (PTI) in the prostatic half. Both effects were abolished by tetrodotoxin or animal pretreatment with 6-hydroxy dopamine (6 OHDA). PTP was markedly reduced by reserpine treatment or tissue incubation with prazosin. PTI was not altered by adrenergic drugs but partially reduced by tissue application of bicuculline or strychnine, revealing that gamma-aminobutyric acid (GABA) may modulate the motor transmission towards the prostatic half of the rat ductus. PMID- 2883615 TI - Baclofen inhibits the spontaneous and visually evoked responses of neurones in the striate cortex of the cat. AB - The effects of iontophoretic application of gamma-aminobutyric acid (GABA) and beta-p-chlorophenyl-GABA (baclofen) on the activity of single neurones in the striate cortex of anaesthetized and paralysed cats were compared. Both compounds inhibited the spontaneous and the visually evoked responses of 92% of the neurones tested (n = 75) and they also eliminated the enhancement of the spontaneous and the evoked responses induced by the microiontophoretic application of glutamate. Bicuculline methiodide (BMI) antagonized the GABA induced inhibition but did not significantly alter the effectiveness of baclofen for most neurones tested. The findings suggest that GABAB receptors are ubiquitous in the striate cortex of the cat. Evidence is presented to suggest that the GABAA and GABAB receptor subtypes differ in their distribution on some striate neurons. PMID- 2883617 TI - Antagonism of mu-opioid receptor-mediated inhibitions of nociceptive neurones by U50488H and dynorphin A1-13 in the rat dorsal horn. AB - We have studied the effects of two highly selective kappa-opioid receptor agonists, U50488H and dynorphin A1-13 on the powerful inhibitions of rat dorsal horn nociceptive neurones produced by the potent mu-opiate receptor agonist, Tyr D-Ala-Gly-Me-Phe-Gly-ol (DAGO). Extracellular single unit recordings were made from 35 convergent neurones which could be excited by impulses in A beta- and C fibre afferents following transcutaneous electrical stimulation of the ipsilateral hind paw. The mu- and kappa-agonists were applied directly onto the surface of the spinal cord. DAGO (0.19, 0.48 and 1.9 nmol) dose-dependently inhibited C-fibre evoked responses with little effect on A beta-evoked activity. The spinal application of dynorphin A1-13 (6.2 nmol) and U50488H (28 nmol) rapidly reversed the spinal inhibitory effect of DAGO indicating that these kappa ligands are likely to act as mu-receptor antagonists in the rat dorsal horn. PMID- 2883616 TI - Primate neostriatal neurons containing tyrosine hydroxylase: immunohistochemical evidence. AB - We have detected, in monkey caudate nucleus and putamen, neuronal cell bodies containing tyrosine hydroxylase-like immunoreactivity, as revealed by peroxidase antiperoxidase immunohistochemistry. Many of these cells are distributed in an outer rim of 1-2 mm throughout the anterior-posterior extent of the neostriatum near its borders with the corona radiata; others are embedded in the adjacent white matter, especially near the ventral putamen and nucleus accumbens. Light and electron microscopy indicate that they are small (8-12 micron), bipolar cells with large nuclei. Such neostriatal neurons, containing tyrosine hydroxylase-like immunoreactivity, number in the tens of thousands. PMID- 2883618 TI - An N-methyl-D-aspartate receptor-independent excitatory action of partial reduction of extracellular [Mg2+] in CA1-region of rat hippocampal slices. AB - Partial reduction of [Mg2+]o from 2 to 1 mM markedly enhanced neuronal responses evoked by Schaffer collateral-commissural fiber stimulation in the CA1-region of rat hippocampal slices. The amplitude of extracellular population potentials recorded in the CA1-pyramidal cell layer and maximum dV/dt of extracellular population EPSP's recorded in the CA1-pyramidal apical dendritic layer were both increased. However, unlike findings from slices where Mg2+ was completely removed from the bathing medium, there was no spontaneous or evoked epileptiform activity, and the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5 phosphonovalerate (2-APV) did not antagonize the enhancement of evoked responses. These results indicate that, in addition to the participation of NMDA receptors in the epileptiform activity observed when Mg2+ is completely removed from the bathing medium, there is also an NMDA receptor-independent excitatory action of partial reduction of [Mg2+]o in hippocampal slices. PMID- 2883619 TI - Treating stage fright in musicians: the use of beta blockers. PMID- 2883621 TI - Regulation of cholesterol biosynthesis. PMID- 2883620 TI - Diazepam restores the increased [3H]glutamate binding to hippocampal synaptic membranes in the amygdaloid-kindled rat. AB - [3H]Glutamic acid binding to hippocampi was increased after amygdaloid kindling in rats, and diazepam inhibited this increased binding, without any effect on the enhanced binding by CaCl2 or the binding in control rats. By inducing kindling in the same way as that used in the binding experiment, the inhibiting effects of diazepam on kindled seizures, the afterdischarge and the development of kindling were observed. PMID- 2883622 TI - A comprehensive analysis of renal DTPA studies. III. Renal artery stenosis. AB - Renal DTPA studies were analysed to produce numerical data of renal function (blood flow, glomerular filtration, and excretion), and this was used as an adjunct to the routine imaging information in a study of renal artery stenosis (RAS). The results show an overall accuracy of 81%, with a sensitivity of 96% and a specificity of 61%. In patients with RAS, beta-blocking drugs reduced the difference between the two kidneys. ACE-inhibiting drugs appeared to preserve renal blood flow but also to cause a deterioration in the glomerular filtration rate of kidneys with RAS. An explanation is proposed, in which renal capillary pressure is more important for function than is renal blood flow. PMID- 2883623 TI - Localization of gamma-glutamyl transpeptidase in the proliferative state of liver. An enzyme histochemical and immunohistochemical study. PMID- 2883624 TI - [Non-free dermatoplasty in the treatment of injuries of the foot and their sequelae]. PMID- 2883625 TI - [Rett's syndrome]. PMID- 2883626 TI - The classification and diagnosis of vasculitis in large and medium-sized blood vessels. PMID- 2883627 TI - Suppurative intracranial complications of upper respiratory tract infections. AB - Suppurative intracranial complications of respiratory infections are relatively rare in children. These complications occur more often in association with chronic sinusitis and chronic otitis media. Because symptoms and signs of the intracranial complications can be nonspecific, a high index of suspicion by the physician is important for early diagnosis. The routine cerebrospinal fluid examination often does not distinguish between the various complications, and radiologic procedures such as radionuclide brain scan, arteriography and computer assisted tomographic scan should be used. Computer-assisted tomographic scan is very useful in detecting early complications allowing trial with medical treatment alone. Appropriate selection of antibiotics must be made on the basis of the likely pathogens in the particular setting and the ability of the antibiotic to penetrate the affected area. Appropriate early management of suppurative intracranial complications should result in a favorable outcome. PMID- 2883628 TI - [Bronchodilator and bronchial hyperreactivity-inhibiting effects of clenbuterol in patients with bronchial asthma]. PMID- 2883629 TI - [Effect of H1 and H2 receptor antagonists on the skin and bronchial reactivity in patients with hay fever]. PMID- 2883630 TI - [Effect of phenformin on the plasma somatostatin level in healthy persons]. PMID- 2883631 TI - MIF-1 and Tyr-MIF-1 antagonize morphine and opioid but not non-opioid stress induced analgesia in the snail, Cepaea nemoralis. AB - The effects of prolyl-leucyl-glycinamide (MIF-1, PLG), tyrosine-prolyl-leucyl glycinamide (Tyr-MIF-1, YPLG) and naloxone on morphine and warm and cold stress induced increases in the latency of the thermal (40 degrees C hot plate) avoidance behaviors of the terrestrial snail, Cepaea nemoralis, were examined. All three substances blocked the morphine- and warm stress-induced opioid analgesia, while having no effects on non-opioid cold stress-induced analgesia. Tyr-MIF-1 had a significantly greater inhibitory effect than MIF-1. These results indicate that MIF-1 and Tyr-MIF-1 antagonize the antinociceptive effects of exogenous opiates and opioid-mediated analgesia in snails in a manner analogous to that described for mammals. This raises the possibility of an evolutionary conservation of functional opioid antagonists. PMID- 2883632 TI - Treatment of pain in cancer patients by intrathecal administration of dynorphin. AB - Dynorphin-(1-13) and -(1-10) were administered by intrathecal injection into six terminal cancer patients at doses of 7.5, 15, 30 and 60 micrograms. Compared with saline, both analogues of dynorphin were effective in suppressing pain. The duration of relief at doses of 15 micrograms and above was more than 4 hours on the average for both peptides. However, no proportional increase in response was observed when the dose applied was doubled. This lack of response might have been due to the development of tolerance. PMID- 2883633 TI - Effect of TRH analog (DN-1417) on tyrosine hydroxylase activity in mesocortical, mesolimbic and nigrostriatal dopaminergic neurons of rat brain. AB - Tyrosine hydroxylase (TH) was assayed in eight regions of rat brain following repeated treatment with a TRH analog, DN-1417 (gamma-butyrolactone-gamma-carbonyl histidyl-prolinamide). Repeated DN-1417 treatment (20 mg/kg/day, IP) for 7 days increased TH activity in the ventral tegmental area and decreased in the prefrontal cortex polar, medial and lateral fields and olfactory tubercles. No significant change in TH activity was found in the nucleus accumbens, striatum and substantia nigra. Kinetic analysis showed that the increased TH activity in the ventral tegmental area was due to an increase in Vmax, but not a change in the apparent Km of TH for a cofactor, 6-methyl-tetrahydropteridine. When TH was assayed at a suboptimal pH and in the presence of a subsaturating cofactor, the striatal TH was activated significantly after DN-1417. In the prefrontal cortex medial field, nucleus accumbens and olfactory tubercles, TH activity assayed under the suboptimal condition was not modified by DN-1417 treatment. These results suggest an intimate involvement of central dopaminergic systems in the actions of DN-1417. PMID- 2883634 TI - An NPY-like peptide may function as MSH-release inhibiting factor in Xenopus laevis. AB - This study demonstrates the presence of a rich plexus of neuropeptide Y (NPY) immunoreactive fibers in the hypothalamus and in the intermediate lobe of the pituitary of Xenopus laevis. During superfusion of neurointermediate lobe tissue, synthetic NPY induces a rapid, powerful and dose-dependent inhibition of in vitro release of MSH, endorphin and other proopiomelanocortin (POMC) derived peptides. Therefore, NPY undoubtedly is one of the growing number of neuropeptides that are likely involved in control of the amphibian MSH cells. Although a number of stimulatory neuropeptides have been found, this is the first neuropeptide to apparently function through an inhibitory mechanism. In that a 2-hr treatment with NPY did not influence POMC biosynthesis, nor processing of this prohormone to smaller peptides, we conclude that the primary action of NPY is a direct effect on the secretory process of the MSH cell. PMID- 2883635 TI - Immunohistochemical studies for multiple peptide-immunoreactivities and co localization of Met-enkephalin-Arg6-Gly7-Leu8, neuropeptide Y and somatostatin in human adrenal medulla and pheochromocytomas. AB - Three normal human adult adrenal medullas and 12 cases of pheochromocytomas were studied for immunohistochemical localization of various peptides. Met-enkephalin Arg6-Gly7-Leu8 (MEAGL) was present in all cases of pheochromocytomas. The normal adrenal medulla showed cells immunoreactive for MEAGL, neuropeptide tyrosine (NPY) and proopiomelanocortin derived N-terminal fragment (NTF). MEAGL and NPY were co-localized in some adrenal medullary cells. Pheochromocytomas showed striking multiple immunoreactivities regardless of histologic types, pleomorphic or organoid. Ten cases showed immunoreactivities for more than two peptides. All cases showed immunoreactivity for MEAGL and 9 cases showed NPY positive cells. Some tumor cells contain both MEAGL and NPY in the cytoplasm. Six cases were positive for somatostatin. Some tumor cells were shown to contain both MEAGL and SS. The appearance of SS and other peptides was considered to be related to the neoplastic transformation of the adrenal medulla. PMID- 2883636 TI - Spinal effects of alpha-endorphin in mice. AB - In male R-3 mice alpha-endorphin (alpha-E) was injected intracerebroventricularly (icv, 10 ng) or intrathecally (ith, 1 or 10 ng). The antinociceptive activity (tail immersion test) and the locomotor activity (photocell actometers) were measured. alpha-E administered icv or ith induced an evident antinociceptive effect which was prevented by the previous naloxone injection. Locomotor activity was inhibited by icv but not ith administration of alpha-E. This effect was not changed by naloxone. The results show that exogenous alpha-E elicits different effects when applied icv or ith, and induces antinociceptive effect at the spinal level through opioid receptors. PMID- 2883637 TI - Comparative studies on antidepressant action of alprazolam in different animal models. AB - Alprazolam, a new benzodiazepine from triazolobenzodiazepine group, produced anxiolytic action in the conflict test with potency similar to that of diazepam. The myorelaxant activity of the drug was relatively weak. Unlike desipramine, alprazolam failed to reduce the immobility of rats in the forced swim test and was unable to prevent clonidine-induced hypothermia. Alprazolam, unlike desipramine, failed also to potentiate behavioral effect of noradrenaline injected into the hippocampus. Alprazolam after acute but not chronic administration antagonized the synchronizing effect of clonidine on EEG pattern. On the other hand, alprazolam similarly to tricyclic antidepressants, prevented the suppression of dominance behavior by clonidine in rats competing for food. The results indicate that alprazolam acts only weakly upon noradrenergic mechanisms related to depression and to antidepressant action of drugs. PMID- 2883638 TI - Are beta- and alpha 2-adrenoceptors co-regulated during their stimulation? Behavioral studies. AB - The effects of beta-, and alpha 1-antagonists on the clenbuterol- and clonidine induced depression of the exploratory activity was measured in rats in the open field test. The ability of clenbuterol (0.5 mg/kg) to reduce exploration was antagonized by 1-propranolol, significantly reduced by rauwolscine and unchanged by corynanthine and prazosin. Clonidine (0.2 mg/kg)-induced hypoactivity was significantly reduced by all the used adrenergic antagonists. A combined treatment with non-sedative doses of clenbuterol and clonidine significantly reduced exploration. Results suggest that both beta- and alpha 2-adrenoceptors are involved in clenbuterol- and clonidine-induced sedation. Moreover, they may indicate the existence of beta- and alpha 2-adrenoceptor interaction. PMID- 2883640 TI - Pharmacotherapy of congestive heart failure. An evaluation of recent advances. AB - Vasodilator therapy represents an important step forward in the treatment of chronic left ventricular failure. Angiotensin converting enzyme (ACE) inhibitors appear to be the most versatile vasodilators, but selected direct-acting vasodilators, sympathetic inhibitors (prazosin), and possibly calcium channel antagonists (nifedipine and diltiazem) may be useful in certain situations. The bipyridine derivatives possess potent inotropic and vasodilating properties. The efficacy of intravenously administered amrinone and milrinone has been proven in the treatment of refractory left ventricular failure. Whether oral administration of milrinone or other bipyridine derivatives will prove to be safe and effective in the long-term treatment of chronic left ventricular failure remains uncertain. PMID- 2883639 TI - Interaction between beta-adrenoceptor agonists and alpha 1-adrenergic system. A behavioral study with the clonidine-induced aggression test. AB - The effects of beta-adrenoceptor agonists on the clonidine-induced aggression in mice were studied. Clenbuterol (0.05-2 mg/kg ip), salbutamol (5-20 mg/kg ip) and terbutaline (10, 20 mg/kg ip) significantly potentiated the effect of clonidine. The enhancement of clonidine aggressiveness induced by clenbuterol (0.5 mg/kg) was prevented by propranolol (2.5, 5 mg/kg) and reduced by prazosin (1 mg/kg). The obtained results provide evidence that stimulation of beta-adrenoceptors facilitates the alpha 1-adrenoceptor-mediated behavior. PMID- 2883641 TI - Stepped-care hypertension therapy. Is it still appropriate? PMID- 2883642 TI - Individualized hypertension therapy. An alternative to stepped-care treatment. AB - A new era in the management of high blood pressure is emerging. A number of drugs, acting by different mechanisms, are appropriate as individualized initial choices for treatment. The control of elevated blood pressure by single-drug therapy, if at all possible, will reduce the frequency of side effects and preserve a decent quality of life. PMID- 2883643 TI - Effects of D-amino acids on growth rate and kidney D-amino acid oxidase in chicks. AB - Studies were conducted on the effects of feeding D-amino acids on growth rate and D-amino acid oxidase (DAAO) in chick kidney. The crystalline amino acid (AA) diet provided seven amino acids either in the L-form or the DL-form at two concentrations (DL- or .5 DL-AA diets) with all diets containing equal amounts of L-amino acids. Weight gains of chicks fed the DL-AA diet were consistently lower than those fed the L- or .5 DL-AA diet. Kidney DAAO activity was significantly higher in chicks fed either the DL-AA or .5 DL-AA diet as compared with the L-AA diet. Kidney DAAO activity was essentially the same in chicks fed the DL- and .5 DL-AA diets. Increasing the nonspecific nitrogen in the diet had no effect in alleviating growth depression of the DL-AA. PMID- 2883644 TI - Antibacterial effect of four phenothiazines. AB - Various types of phenothiazines were examined for antibacterial effect on 61 Gram positive and Gram-negative bacterial strains in vitro. The investigated phenothiazines were two neuroleptic drugs, fluphenazine and chlorpromazine, and two antihistaminic drugs, alimemazine and promethazine. All four drugs have antibacterial effects in vitro, the phenothiazines being more potent against the Gram-positive microorganisms. The antibacterial potency of the drugs was measured as IC50: Fluphenazine 29 microM (15 micrograms/ml), alimemzaine 49 microM (37 micrograms/ml), promethazine 88 microM (28 micrograms/ml) and chlorpromazine 92 microM (29 micrograms/ml). The antibacterial potency of the drugs was linked neither to the neuroleptic nor the antihistaminic potency of the drugs, which is in agreement with results of earlier stereoisomeric investigations. Thus, the known phenothiazines may represent a pool of potentially new antimicrobial drugs. A therapeutic application of these results, however, requires additional in vitro an in vivo testing in an animal model. The bacterial model might be of value as a model system in the study of the interaction of neuropharmacological agents and other membrane active compounds on biological membranes. PMID- 2883645 TI - Beta 1- and beta 2-adrenoceptor affinity and stimulatory effects of (S)-pindolol and iodinated (S)-pindolol. AB - The beta 1- and beta 2-adrenoceptor affinity and stimulatory effects of iodinated (S)-pindolol (IPIN) and (S)-pindolol were investigated in vitro using beta adrenoceptor binding technique and isolated right atrium (rate increase, beta 1) and uterus (relaxation, beta 2) of the rat. IPIN had a higher affinity towards beta-adrenoceptors compared to (S)-pindolol, with some beta 2-adrenoceptor selectivity. In the rat uterus, IPIN produced only marginal stimulatory effects, while (S)-pindolol caused a concentration-dependent relaxation with a maximal effect that was 55% of that generated by isoprenaline. In the right atrium IPIN caused an increase in the atrial rate similar to that caused by (S)-pindolol. The concentration of IPIN required in the right atrium for a half-maximal response (pD2 = 7.81) was markedly greater than that required for occupation of half the beta-adrenoceptor population (pKB = 9.81). The beta 1-selective blocker metoprolol antagonized the effect of (S)-pindolol and IPIN on the atrial rate but a greater concentration of metoprolol (5 X 10(-6) M compared with 5 X 10(-7) M) was required to antagonize the effect of IPIN significantly. It is concluded that iodination of (S)-pindolol increased its affinity and decreased its efficacy towards beta-adrenoceptors. PMID- 2883646 TI - Hormonal control of pancreatic cancer growth. AB - The effects of epidermal growth factor (EGF) and somatostatin-14 (SS) on growth of Mia PaCa-2 cells in cell culture were examined. EGF had no effect on cell growth in sera containing media but significantly increased growth in sera-free media. The effect of EGF was complete within 18 h. SS added with EGF entirely eliminated the growth stimulation of EGF. SS added to cells in culture with sera inhibited their growth as well. PMID- 2883647 TI - Watery diarrhea syndrome caused by multihormonal malignant pancreatic islet cell tumor secreting somatostatin, vasoactive intestinal peptide, serotonin, and prostaglandin E--a clinicopathological, biochemical, immunohistochemical, and ultrastructural study. AB - The pathophysiological, biochemical, histological, ultrastructural, and immunohistochemical characters of a case of malignant pancreatic islet cell tumor with watery diarrhea syndrome were carefully investigated. Four hormones or mediators--somatostatin (SST), vasoactive intestinal peptide (VIP), serotonin, and prostaglandin E--were markedly elevated in the circulation. The diagnosis was further confirmed by exploratory laparotomy and autopsy. The contents of SST and VIP in tumor tissues were very high. Gel chromatography of tumor extract revealed single peaks for both SST and VIP. Immunohistochemical studies of tumor tissues showed numerous immunoreactive cells to anti-SST, moderate amount of VIP-positive cells, and a few hCG-, insulin-, and glucagon-positive cells. In conclusion, this is an unusual case of Verner-Morrison syndrome in which three kinds of bioactive hormones or mediators were simultaneously secreted; peptides, amine, and prostaglandin. PMID- 2883648 TI - A comparison of the effects of two somatostatin analogues in a patient with an external pancreatic fistula. AB - In a 30-year-old man, a total external pancreatic fistula developed after enucleation of an insulinoma of the head of the gland. The output of the fistula was reduced to some extent by total parenteral nutrition. Much greater reductions of volume were noted during short-term administration of two somatostatin preparations, SMS 201-995 and Somatofalk, for 1 week consecutively. Although the former showed several advantages over the latter drug, such as absence of an escape phenomenon and of a rebound effect, neither drug caused a closure of the fistula. Spontaneous closure of the fistula occurred after 3 1/2 months. PMID- 2883649 TI - Frontiers in pancreatic physiology. PMID- 2883650 TI - Noncompliance in schizophrenia. AB - Compliance research is reviewed with particular reference to neuroleptic treatment of schizophrenia. Reported noncompliance rates of up to 50 per cent are likely to be an underestimate. Models of compliance and health-seeking behaviour borrowed from physical medicine are of questionable relevance to schizophrenia where perception of illness is often distorted. Factors thought to be implicated in noncompliance need to be evaluated and a theoretical model applicable to schizophrenia constructed. In the meantime there is evidence to suggest that behavioural intervention strategies may be superior to simple educational ones in the management of noncompliance. A discussion of methodological issues relating to the assessment of compliance is offered and a strategy for further research outlined. PMID- 2883651 TI - Periodic crosslinking of microtubules by cytoplasmic microtubule-associated and microtubule-corset proteins from a trypanosomatid. AB - The dominant element in the cytoskeleton of Crithidia fasciculata is a peripheral corset of microtubules enclosing the cell body and closely underlying the plasma membrane. A lateral spacing of 50 nm is maintained by crosslinks, and microtubules may also be linked to the plasma membrane. We have characterized groups of polypeptides that associate with microtubules polymerized in vitro from the cytoplasm, or that are associated with the corset complex. They differ except for one of Mr 33,000 present in both groups. The corresponding native corset protein appears to be a dimer of Mr 66,000. These protein(s) copolymerize with brain tubulin, and the resultant polymer consists of pairs or small parallel bundles of microtubules, joined by periodic crosslinks spaced about 8.5 nm apart. PMID- 2883652 TI - Detection of human DNA polymorphisms with a simplified denaturing gradient gel electrophoresis technique. AB - Single base pair differences between otherwise identical DNA molecules can result in altered melting behavior detectable by denaturing gradient gel electrophoresis. We have developed a simplified procedure for using denaturing gradient gel electrophoresis to detect base pair changes in genomic DNA. Genomic DNA is digested with restriction enzymes and hybridized in solution to labeled single-stranded probe DNA. The excess probe is then hybridized to complementary phage M13 template DNA, and the reaction mixture is electrophoresed on a denaturing gradient gel. Only the genomic DNA probe hybrids migrate into the gel. Differences in hybrid mobility on the gel indicate base pair changes in the genomic DNA. We have used this technique to identify two polymorphic sites within a 1.2-kilobase region of human chromosome 20. This approach should greatly facilitate the identification of DNA polymorphisms useful for gene linkage studies and the diagnosis of genetic diseases. PMID- 2883653 TI - Isolation and characterization of the alpha-sialyl-beta-2,3-galactosyl-specific adhesin from fimbriated Escherichia coli. AB - The alpha-sialyl-beta-2,3-galactosyl-specific adhesin (S adhesin) was isolated from cells of a recombinant Escherichia coli K-12 strain expressing the S fimbrial adhesin complex. A crude cell extract was partially dissociated into fimbriae and an adhesin-enriched fraction by heating to 70 degrees C. From the latter, adhesin was purified to apparent homogeneity (by fast protein liquid chromatography, immunoblot, and NaDodSO4/PAGE) by differential ammonium sulfate precipitation, dissociation in 8 M guanidine hydrochloride, and high-resolution anion-exchange chromatography in 8 M urea. The purified adhesin formed an aggregate of Mr approximately 10(6) that was made up of one type of 12-kDa polypeptide (fimbrillin is 16.5 kDa). It had pI value of 4.7 (fimbriae has a pI value of 6). Adhesin and fimbrillin had different amino acid compositions. The purified adhesins agglutinated human and bovine erythrocytes with the same specificity as the whole bacteria; purified fimbriae were not adhesive. Monoclonal anti-adhesin and anti-fimbriae antibodies were obtained. Monoclonal anti-adhesin, but none of the anti-fimbriae, antibodies inhibited the agglutination of erythrocytes. The anti-adhesive antibodies were used in immuno gold electron microscopy to localize adhesin exclusively on the fimbriae, with a possible preference to their tips. PMID- 2883654 TI - Opposing effects of a ras oncogene on growth factor-stimulated phosphoinositide hydrolysis: desensitization to platelet-derived growth factor and enhanced sensitivity to bradykinin. AB - Expression of a transforming Harvey or Kirsten ras gene caused opposing effects in the ability of platelet-derived growth factor (PDGF) and bradykinin to activate phospholipase C-mediated phosphoinositide hydrolysis. In [3H]inositol labeled rat-1 fibroblasts, PDGF (5 ng/ml) resulted in a 2-fold increase in the level of [3H]inositol trisphosphate (InsP3) after 2 min and, in the presence of LiCl, a 3- to 8-fold increase in the level of [3H]inositol monophosphate (InsP1) after 30 min. However, in EJ-ras-transfected rat-1 cells, which exhibit near normal levels of PDGF receptors, PDGF resulted in little or no accumulation of either [3H]InsP3 or [3H]InsP1. Similarly, marked stimulations by PDGF were observed in NIH 3T3 cells, as well as in v-src-transformed 3T3 cells, but not in 3T3 cells transformed by Kirsten sarcoma virus or by transfection with v-Ha-ras DNA. This diminished phosphoinositide response in ras-transformed cells was associated with a markedly attenuated mitogenic response to PDGF. On the other hand, both phosphoinositide metabolism and DNA synthesis in ras-transformed fibroblasts were stimulated several-fold by serum. In NIH 3T3 cells carrying a glucocorticoid-inducible v-Ha-ras gene, a close correlation was found between the expression of p21ras and the loss of PDGF-stimulated [3H]InsP1 accumulation. In contrast to this ras-induced desensitization to PDGF, ras-transformed NIH 3T3 cells exhibited an enhanced sensitivity to bradykinin; this effect was associated with an elevated level of high-affinity [3H]bradykinin binding. We propose that a ras gene product (p21) can, directly or indirectly, influence growth factor stimulated phosphoinositide hydrolysis, as well as DNA synthesis, via alterations in the properties of specific growth factor receptors. PMID- 2883655 TI - Use of phoA gene fusions to identify a pilus colonization factor coordinately regulated with cholera toxin. AB - The transposon TnphoA was used to generate fusions between phoA, the gene for alkaline phosphatase (PhoA), and genes encoding proteins that are secreted by Vibrio cholerae. One of the PhoA+ mutants isolated showed a dramatic reduction in its ability to colonize the intestines of suckling mice. This mutant no longer produced a 20.5-kDa protein (TcpA) that we show is the major subunit of a V. cholerae pilus. Amino-terminal sequence analysis of the TcpA pilus subunit showed that it shares amino acid homology with the pilins produced by several other pathogenic bacteria. The TcpA pilus was coordinately expressed with cholera toxin under various culture conditions, and this effect appeared to be dependent on the transcriptional activator encoded by the toxR gene. We conclude that the toxR gene plays a central role in the transcriptional regulation of multiple virulence genes of V. cholerae. PMID- 2883656 TI - Molecular cloning and expression of T11 cDNAs reveal a receptor-like structure on human T lymphocytes. AB - The T11 (CD2) sheep-erythrocyte-binding protein is a T-cell surface molecule involved in activation of T lymphocytes and thymocytes, including those lacking the T3-Ti antigen-receptor complex. The primary structure of T11 was deduced from protein microsequencing and cDNA cloning. The mature human protein appears to be divided into three domains: a hydrophilic 185 amino acid external domain bearing only limited homology to the T-cell surface protein T4 and the immunoglobulin kappa light chain variable region, a 25 amino acid hydrophobic transmembrane segment, and a 126 amino acid cytoplasmic domain rich in prolines and basic residues. Transfection of cDNAs encoding either the 1.7- or the 1.3-kilobase T11 mRNA into COS-1 cells resulted in expression of surface T11 epitopes as well as sheep-erythrocyte-binding capacity. The predicted structure is consistent with the possibility that T11 functions in signal transduction. PMID- 2883658 TI - Neural activity in hypothalamic and genetic obesity. PMID- 2883657 TI - Genomic and cDNA actin sequences from a virulent strain of Entamoeba histolytica. AB - Invasiveness of Entamoeba histolytica strains that cause acute amoebiasis is characterized by aggressive behavior associated with cell motility and actin function. Analysis of actin genes from E. histolytica was initiated by devising methods for the isolation of biologically active nucleic acids, which allowed the preparation of cDNA and genomic DNA libraries. E. histolytica actin-encoding cDNAs and genomic clones have been isolated from libraries prepared from the virulent HM1:IMSS strain using a heterologous actin probe. Nucleotide sequence analysis of three independent cDNA clones and one genomic clone reveals a highly unusual codon bias and the absence of intervening sequences in E. histolytica actin. The coding sequence of the genomic clone is identical to that of two of the three cDNA clones. These represent at least two distinct mRNAs differing only by five silent changes in the protein coding sequence. Multiple genomic copies of the actin gene can be detected by Southern hybridization. E. histolytica actin exhibits a higher degree of homology to cytoplasmic than to muscle actin. Although the protein has been shown not to bind DNase I, the inferred amino acid sequence indicates conservation of all residues implied to participate in this binding. PMID- 2883659 TI - Neural control of the endocrine pancreas. PMID- 2883660 TI - Tissue somatostatin levels in three models of genetic obesity in rats. AB - A potential role for somatostatin (SRIF) in the pathogenesis of the hyperinsulinemia of obese rats was considered. SRIF like immunoreactivity (ng/mg protein) was therefore measured in hot 2 N acetic acid extracts of pancreas, stomach, pituitary, and hypothalamus in tissues obtained from three models of genetic obesity in rats. These models included the obese and lean controls of LA/N-cp, SHR/N-cp, and Zucker rats. To assess the effects of diet on SRIF levels, mixed diets were provided ad lib which contained a carbohydrate as either sucrose or starch. Some groups were fed chow diets. No significant dietary effects on tissue levels of SRIF were obtained. However, two of the three models (Zucker and SHR/N-cp) showed phenotypic effects on SRIF levels in pancreas; namely, obese rats showed a significantly greater concentration of SRIF (P less than 0.0005 and less than 0.0002, respectively) than did the lean littermates. These findings were confirmed by measurement of total pancreas SRIF content. Gastric levels were significantly altered only in the obese Zucker rats (P less than 0.005) where obese tissues had lower concentrations than those of lean animals. However similar directional changes in pancreas and stomach were observed in all models. It is concluded that the hyperinsulinemia of the obese animals studied is not due to absolute deficiency in pancreatic SRIF content. It is postulated however that decreased pancreatic SRIF secretion (paracrine or otherwise) relative to pancreatic insulin content could still play a role. PMID- 2883661 TI - Inhibitory effects of somatostatin analogs on prolactin secretion in rats pretreated with estrogen or haloperidol. AB - The effect on prolactin (PRL) secretion of acute administration of new octapeptide analogs of somatostatin (SS) with an enhanced and prolonged growth hormone inhibitory activity was investigated in rats under various pretreatment conditions with estrogen and antidopaminergic drugs. Analog D-Phe-Cys-Tyr-D-Trp Lys-Val-Cys-Thr-NH2 (RC-121), at a dose of 5 micrograms/100 g body wt, did not decrease basal PRL levels in thiopental-anesthetized female rats, untreated or treated with estrogen benzoate (EB) (8 micrograms/rat) for 5 days. When haloperidol was used to elevate PRL level, a single injection of RC-121 inhibited PRL release in EB-pretreated female rats or untreated female and male rats. Analog D-Phe-Cys-Trp-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), which has a potency similar to RC-121 in the tests on inhibition of GH, in a dose of 0.2 microgram/100 g body wt, did not lower the elevated PRL level induced by alpha methyl-p-tyrosine and/or pretreatment with EB (100 micrograms/rat, 3 and 6 days before) in pentobarbital-anesthetized male rats. However, both analogs RC-121 and RC-160, in doses of 0.2 microgram/100 g body wt, decreased the PRL levels elevated by prolonged pretreatment with EB (100 micrograms/rat, twice a week for 3 weeks) in male rats. These results indicate that acute administration of these SS analogs can induce a prolonged inhibition of PRL release when PRL is acutely elevated by haloperidol or chronically elevated by 3 weeks of estrogen administration. Future additional studies are required to investigate the effects of chronic administration of these SS analogs on PRL levels. PMID- 2883662 TI - A competitive receptor binding radioassay for beta-1 and beta-2 adrenergic agents. AB - A rapid and sensitive competitive receptor binding assay for beta-1 and beta-2 adrenergic binding for adrenergic agents has been developed. The steps that are critical for the success of the assay are given in detail so that the assay can be set up in any routine laboratory with relative ease. The rationale behind the use of specific reagents is discussed. The assay requires microgram quantities of test compound, a radiolabeled specific beta adrenergic antagonist [3H]dihydroalprenolol (DHA), and turkey erythrocyte beta-1 and rat erythrocyte beta-2 receptor membranes. Serial dilutions of sample are incubated with appropriate receptor membranes and DHA for 1 hr at room temperature. After equilibrium is attained, the bound radioligand is separated by rapid filtration under vacuum through Whatman GF/B filters. The amount of bound DHA trapped on the filter is inversely proportional to the degree of beta-1 or beta-2 adrenergic binding of the sample. Separation of bound from free radioligand by filtration permits rapid determination of a large number of samples. This assay quantitates and differentiates beta-1 and beta-2 adrenergic binding of synthetic adrenergic agents. PMID- 2883663 TI - Dopaminergic and alpha 1-adrenergic properties of B-HT920 revealed in morphine dependent rats. AB - B-HT920 is known to be a selective alpha 2-adrenoceptor agonist, and has been used in a study on morphine-withdrawal in rats. In accordance with other alpha 2 agonists B-HT920 was found to potentiate "jumping" and to reduce "body shakes." However, B-HT920 did not suppress body weight loss. Furthermore, it induced strong salivation and prevented ptosis (described for the alpha 1-adrenergic agonist ST-587). Rearing and locomotor activity appeared to be enhanced, an effect shared by dopamine-agonist lisurid. The effects of B-HT920 have been specified using the alpha-adrenergic antagonists yohimbine and prazosin and the dopamine antagonist haloperidol. Yohimbine could not antagonize any of the actions of B-HT920. However the increase in rearing and locomotion was blocked by haloperidol. The induction of salivation was prevented by prazosin. Pretreatment with prazosin showed a decrease in the loss of body weight caused by B-HT920, while pretreatment with yohimbine showed that B-HT920 induced an increased loss in body weight. These data suggest that B-HT920 under certain conditions exerts dopamine-agonistic actions in stimulating locomotor activity and alpha 1 adrenergic actions in inducing salivation and enhanced loss of body weight. PMID- 2883664 TI - Locomotor activity as a predictor of times and dosages for studies of nicotine's neurochemical actions. AB - Nicotine's action on the central nervous system is complex and likely involves an interaction of neurotransmitters. To determine the time after administration of nicotine and dosage for neurochemical studies, locomotor activity of CD-1 mice was determined at 5 min intervals between 0-60 min. A low nicotine dosage (0.05 mg/kg) did not alter activity 5-15 min after drug injection, but increased activity 28% at 15-25 min post-injection. A high dosage (0.8 mg/kg) reduced total distance 62% and rearing 87% at 5-15 min; at 15-25 minutes total distance declined 56% and rearing 69%; all measures returned to control values after 30 minutes; rearing then increased at 40 min after nicotine. Pretreatment (15 min before nicotine) with mecamylamine (1.0 mg/kg), but not hexamethonium (1.0 mg/kg), prevented the depressant effect of nicotine. Dopamine (DA) and its metabolites as well as acetylcholine (ACh) synthesis were measured at the point of nicotine's maximal depressant action. Striatal levels of dihydroxyphenylacetic acid (DOPAC) were increased and ACh utilization was reduced in striatum (-25%) and cortex (-24%) 10 min after nicotine (0.8 mg/kg). Mecamylamine, while preventing the depressant effect of nicotine on locomotor activity, did not alter its effects on DA metabolism. These results demonstrate that the behavioral outcome of acute nicotine treatment is time and dose-dependent. Nicotine's depressant action appears not to be due to altered DA but may be related to changes in carbohydrate and acetylcholine metabolism. PMID- 2883665 TI - Effects of phencyclidine, ketamine and MDMA on complex operant behavior in monkeys. AB - In one component of a multiple schedule, patas monkeys acquired a different four response chain each session by responding sequentially on three levers in the presence of four numerals (acquisition). In the other component, the four response chain was the same each session (performance). The response chain in each component was maintained by food presentation under a fixed-ratio schedule. After IM administration, phencyclidine, ketamine, and MDMA (3,4 methylenedioxymethamphetamine or "ecstasy") each produced dose-related decreases in overall response rate in both schedule components, though ketamine and MDMA were less potent (on a mg/kg basis) than phencyclidine. At high doses of each drug, the marked decrease in overall response rate was due primarily to a long initial pause. Ketamine was similar to phencyclidine in producing dose-related increases in percent errors in both schedule components, but the maximal error increasing effect was considerably smaller with ketamine. This quantitative difference appeared to be related to the shorter duration of ketamine's effects on accuracy. Unlike phencyclidine and ketamine, MDMA had no effect on accuracy in either acquisition or performance. The results indicate that MDMA disrupts complex operant behavior to a lesser extent than phencyclidine-type drugs. PMID- 2883666 TI - The effect of MDMA ("Ecstasy") and its optical isomers on schedule-controlled responding in mice. AB - Eleven mice were trained to respond under an FR 20 schedule of reinforcement and, after learning the schedule, were administered doses of saline and the following phenylisopropylamines: (+/-)-MDMA, S(+)-MDMA, R(-)-MDMA and (+)-amphetamine. Each of the phenylisopropylamines decreased rates of operant responding in a dose dependent manner. S(+)-MDMA (ED50 = 3.1 mg/kg) was nearly equipotent with racemic MDMA and four times more potent than R(-)-MDMA (ED50 = 4.1 and 11.6 mg/kg, respectively), but less potent than (+)-amphetamine (ED50 = 0.74 mg/kg). The present study constitutes the first enantiomeric behavioral-potency comparison for the optical isomers of MDMA. PMID- 2883668 TI - Benzodiazepine self-administration in rhesus monkeys: estazolam, flurazepam and lorazepam. AB - The ability of three benzodiazepines to maintain self-administration behavior was studied in rhesus monkeys using a substitution procedure. Lever-press responding was maintained in six monkeys under a fixed-ratio schedule of IV pentobarbital delivery in daily sessions of 3 hr duration. Each of several doses of flurazepam, lorazepam and estazolam as well as saline and vehicle was periodically substituted for 4-13 consecutive sessions. Between dose or vehicle substitutions, responding was maintained by pentobarbital. All six monkeys self-administered flurazepam above vehicle or saline levels. In addition four of five monkeys tested with lorazepam and four of six tested with estazolam self-administered at least one dose of drug above control levels. These results indicate that self administration performance can be reliably maintained in rhesus monkeys by certain benzodiazepines under appropriate experimental conditions. PMID- 2883667 TI - The nociceptive jaw-opening reflex: evidence for alpha 2 adrenoceptor involvement. AB - The ability of alpha adrenoceptor agonists to modulate the tooth pulp stimulation evoked (TPS) jaw-opening reflex (JOR) was investigated in rats and rabbits. Low doses of clonidine (6.25-50 micrograms/kg, IV) significantly increased dEMG thresholds. These effects were antagonized by alpha 2 adrenoceptor antagonists (e.g., yohimbine), but not by alpha 1 adrenoceptor antagonists (e.g., prazosin) or mu receptor antagonists (e.g., naloxone). Polar alpha 2 adrenoceptor agonists (e.g., ST-91 and 4-hydroxyclonidine) that cross the blood brain barrier (BBB) poorly and lipophilic alpha 1 adrenoceptor agonists (e.g., ST-587) that cross the BBB easily were without affect on the TPS-JOR. Structures of the peripheral efferent neurocircuitry of the JOR (e.g., the digastric muscle and the neuromuscular junction of the digastric muscle and its motor nerve, the mylohyoid) were shown not to be active sites of clonidine's effect on the TPS JOR. Treatment with phentolamine (an alpha adrenoceptor antagonist that poorly crosses the BBB) completely poorly crosses the BBB) completely antagonized clonidine's initial transient cardiovascular (pressor) effect without altering its TPS-JOR effects. Pretreatment with reserpine (a catecholamine depleting agent) failed to alter clonidine's affects on the TPS-JOR. Our studies suggest that alpha 2 adrenoceptors potently modulate the TPS-JOR and such modulation may be important in understanding trigeminal neuronal circuitries that partake in pain processing. PMID- 2883671 TI - Studies on phenothiazines: synthesis of phenothiazines via Smiles' rearrangement. PMID- 2883669 TI - The effect of neurotransmitters on cataleptic behavior induced by PG D2 in rats. AB - The effects of several neurotransmitters on prostaglandin (PG) D2-induced cataleptic behavior in rats were investigated by the high bar test. Intracerebroventricular administration of PG D2 elicited cataleptic behavior in a dose-dependent manner without producing a marked change in spontaneous motor activity. The incidences of cataleptic behavior were 20% and 100% at doses of 2 nmol and 50 nmol of PG D2, respectively. Intraperitoneal pretreatment with L-DOPA (100 mg/kg), apomorphine (1 mg/kg), amantadine (0.2 mg/kg), atropine (0.5 mg/kg) or p-chlorophenylalanine (300 mg/kg) significantly decreased the cataleptic behavior induced by 50 nmol of PG D2. Conversely, simultaneous treatment with 5 hydroxy-L-tryptophan (30 mg/kg), 5-methoxy-N,N-dimethyltryptamine (5 mg/kg), imipramine (20 mg/kg) or clomipramine (10 mg/kg) markedly increased the cataleptic behavior induced by 2 nmol of PG D2. Propranolol (10 mg/kg) and phenoxybenzamine (10 mg/kg) did not affect the induction of cataleptic behavior by either 2 nmol or 50 nmol of PG D2. These results suggest that PG D2 might be involved in inducing cataleptic behavior by modulating serotonergic, cholinergic and dopaminergic systems. PMID- 2883670 TI - Famotidine and ranitidine: any difference in the duration of action? AB - The new H2-receptor antagonist famotidine was studied to test its duration of action in comparison with ranitidine. In the conscious cat provided with gastric fistula famotidine and ranitidine, administered by bolus i.v. injection, by continuous infusion or intragastrically, had an inhibitory effect on dimaprit induced acid secretion which lasted similarly. The only difference between the two compounds was the higher potency of famotidine. Reversibility studies carried out in the isolated gastric fundus from immature rats showed that famotidine, like ranitidine, was easily washed out even at the highest concentration tested (3 X 10(-6) M) and thus it can be considered a readily dissociable H2 antagonist in this tissue. PMID- 2883672 TI - A partially rigid butyrophenone analog with extended conformation. AB - The synthesis and in vitro dopamine D2 receptor binding of a conformationally restricted analog of 4-piperidinobutyrophenone is described. 2-(2 Piperidinoethyl)-1-tetralone displaces [3H]spiperone from the rat striatal dopamine receptor with an IC50 of 1.2 X 10(-4)mol/l. PMID- 2883673 TI - [Interaction between macromolecular adjuvants and drugs. 25. The effect of cellulose ether on the solubility characteristics of benzodiazepine derivatives]. AB - The technological processing of the benzodiazepine derivatives chlordiazepoxide, medazepam, diazepam, nitrazepam and clonazepam with methyl cellulose (mc) and hydroxyethylcellulose--especially physical mixtures and evaporates--led to an improved dissolution of the problem drugs. The effect of the adjuvants is remarkable in the initial phase of the dissolution and very distinctive at the end of the experiment. Obviously there is no relation between saturation solubility and dissolution. Only with nitrazepam and clonazepam, but less clearly with medazepam, an increase of solubility by the mc-trituration was observed. Studies of the binding showed a concentration and temperature dependent interaction of the benzodiazepines diazepam, clonazepam, medazepam and nitrazepam, to mc. As X-ray diffraction and differential thermoanalysis gave no interpretation for the improved dissolution behaviour of drug/adjuvant preparations, it is assumed that a high distribution of the drug particles in the dissolution medium by the preceding treatment with cellulose ether is the main reason for the increase of the dissolution rate. PMID- 2883674 TI - [The exclusion of nonspecific effects in testing potential anti-inflammatory agents following intraperitoneal administration]. AB - The intraperitoneal (i.p.) administration of potential antiphologistics of the group of DL-2-phenylglycinalkylester hydrochlorids caused beside the inhibition of the carrageenan rat paw oedema a high increase of the glucocorticoid-induced tyrosin transaminase activity (TTA) in the liver. Using this group of compounds the exclusion of unspecific antiphlogistic effects as a consequence of peritoneal irritation and glucocorticoid liberation was studied. For comparison phenylbutazone, hydrochlorid acid and carrageenan were examined after i.p. administration. The results showed that in contrast to hydrochlorid acid and carrageenan the antiphlogistic effects of DL-2-phenylglycinalkylester hydrochlorids were not elicited by unspecific irritation. Therefore the i.p. administration can be used in testing antiinflammatory drugs, if indirect effects have been excluded in adrenalectomized animals. The determination of the TTA activity of the liver as an indicator of glucocorticoid liberation is not sufficient for exclusion of unspecific effects in testing antiphlogistics after i.p. administration. PMID- 2883675 TI - Tiotidine and ICIA 5165 inhibit central and peripheral H2 receptors with equal potency. AB - Histamine, acting through H2 receptors, increases cAMP formation in homogenates of guinea pig hippocampus. The activities of two H2 antagonists, tiotidine and ICIA 5165, as inhibitors of the histamine-induced increase were investigated. ICIA 5165 and tiotidine were potent antagonists of histamine with a pKi of 8.0 and 7.6, respectively. Similarly, the positive chronotropic response of isolated guinea pig atria to histamine was antagonized by tiotidine and ICIA 5165 with a pKB of 7.8 and 7.9, respectively. These studies suggest that histamine H2 receptors in the CNS and atria are similar. PMID- 2883676 TI - Classification of neuroleptics--zotepine. AB - Neuroleptic classifications try to take account of both biological effects (interaction with different neurotransmitters, selectivity of action on dopaminergic structures or dopaminergic subclasses of receptors) and clinical effects (sedative properties, efficacy on positive or negative symptomatology of schizophrenia, antimanic effect). Zotepine blocks mainly dopaminergic, 5-HT 2 and alpha 1 receptors. It should therefore be expected to have sedative properties in humans and to be effective against mania and the positive symptoms of schizophrenia. PMID- 2883677 TI - Comparative placebo-controlled pharmacodynamic studies with zotepine and clozapine utilizing pharmaco-EEG and psychometry. AB - In a double-blind, placebo-controlled study the encephalotropic and psychotropic properties of zotepine - a new tricyclic dibenzothiepine with antidopaminergic, adrenolytic and antiserotoninergic properties - were investigated utilizing quantitative EEG, psychometric and psychophysiological tests as well as clinical observations. Fifteen normal volunteers received randomized (latin square design) and at weekly intervals single oral doses of placebo, 25 mg, 50 mg and 100 mg zotepine as well as 50 mg clozapine as reference compound. Plasma samplings for blood levels, EEG recordings, and evaluation of blood pressure, pulse rate and side-effects were carried out at the hours 0, 1, 2, 4, 6 and 8, while psychometric data were recorded at the same time except the first hour. Computer assisted spectral analysis of the EEG demonstrated after all three doses significant changes as compared with placebo characterized by an augmentation of delta and theta activity, decreased of alpha and beta activity, slowing of the centroid of the total activity and alpha activity, and decrease of the dominant frequency and its absolute and relative power. Such changes are typical for low potency basic neuroleptics of the sedative type such as chlorpromazine. Clozapine also augmented slow activities, decreased alpha activity, the dominant frequency and the alpha centroid, but induced in contrast to zotepine a concomitant increase of fast beta activity, acceleration of the beta centroid and no slowing of the dominant frequency, while the total power was significantly attenuated. These findings confirm earlier reports about the pharmaco-EEG profile of clozapine, which has a resemblance to profiles of anticholinergic antidepressants of the amitriptyline type. Psychometric tests demonstrated after the higher doses of zotepine and clozapine a deterioration of noopsychic and thymospsychic functions which was more pronounced after the reference compound than after zotepine. The lowest dose of zotepine, 25 mg, even produced an improvement in numerical memory and complex reaction. CFF, skin conductance, pupillary diameter and pupillary response measurements decreased after both compounds. Dose-efficacy calculations showed 100 mg zotepine and clozapine to be the most CNS-effective compounds, followed by 50 mg and 25 mg zotepine, while placebo induced the least changes. Time-efficacy calculations showed neurophysiological and behavioral peak effects after zotepine at the 4th and 6th hour, as compared with the 2nd and 4th hour after clozapine. Pulse rate increased with both compounds; blood pressure decreased after clozapine but remained unchanged after zotepine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2883679 TI - Clinical experience with the neuroleptic zotepine--first results. AB - The few patients examined in the pilot study so far lead us to believe that the new neuroleptic drug zotepine is a substance with good antipsychotic effectiveness. Among the side-effects, a marked sedative component is apparent which is perceived as being unpleasant by all patients due to its expression in the form of drowsiness and lack of vitality during the day. Here, problems with patient compliance may possibly arise. Extrapyramidal motor side-effects could not be observed except in one case in which therapy was consequently terminated. The changes observed in the EEG were interpreted as an increase in cerebral excitability, an effect known to be possible in connection with the administration of neuroleptic drugs. Altogether, on the basis of our first clinical experience with the new neuroleptic zotepine, we feel that this drug doses not yield a marked improvement in regard to the ratio of effect to side effect when compared with the other neuroleptic drugs available at the present time. Our findings, however, tend to support suggestions in the literature that zotepine may have a better effect than other drugs on patients' negative symptoms. PMID- 2883678 TI - Clinical and neuroendocrine effects of zotepine--a new neuroleptic drug. AB - Zotepine, a new neuroleptic, was administered to 23 hospitalized patients with schizophrenia at doses of 75 to 600 mg/d for 21 to 42 days. Based upon analysis of conventional rating scales we observed a significant improvement (P less than 0.001) during week 1, which compound throughout the study period. After 21 days we identified 17 responders and 6 nonresponders, 2 of whom dropped out of the study because of a tonic-clonic seizure in one case and withdrawal of consent to further participation in the second case. During further treatment the improvement remaind stable in the responder group, while 1 nonresponder improved after 3 weeks of treatment. In 9 patients extrapyramidal symptoms were observed (6 parkinsonism, 2 early dyskinesia, 1 parkinsonism and early dyskinesia), which required sporadic (n = 3) or continuous (n = 2) treatment with biperiden in 5 cases. This low incidence of extrapyramidal symptoms necessitating coadministration of anticholinergic drugs suggests that the risk of inducing parkinsonism and dyskinesias during zotepine treatment is low. Comparison of cortisol, growth hormone and prolactin release in normal controls challenged with 25 mg zotepine showed that only prolactin secretion is increased, while secretion of cortisol and growth hormone remains unaffected. The clinical effects observed in the present study show that zotepine has potential value in the treatment of schizophrenia. The findings warrant further study in controlled trials. PMID- 2883680 TI - Comparison of efficacy of zotepine and thiothixene in schizophrenia in a double blind study. AB - Zotepine and thiothixene were compared for clinical efficacy and safety in a double-blind trial. Using overall improvement ratings and Gorham's BPRS, zotepine rated higher improvement in motor retardation, suspiciousness, mannerisms and posturing symptoms, suggesting that it has both activating and antipsychotic activities. Thiothixene produced higher improvement ratings in symptoms such as hallucinatory behavior, somatic concerns, anxiety, guilt feelings, tension, depressive mood and uncooperativeness. As for side effects, there was a significantly lower frequency of dry mouth and insomnia with zotepine when compared with thiothixene. The lower incidence of insomnia is interesting in view of zotepine's clinical activating effects. There were no abnormal laboratory findings. PMID- 2883681 TI - Profiles of clinical efficacy and pharmacological action of zotepine. AB - Zotepine, a new neuroleptic drug synthesized in Japan has unique profiles in the treatment for schizophrenic patients, such as a low incidence of extrapyramidal symptoms and a biphasic effect; activation and sedation. It also shows unique pharmacological actions. The author discussed the relationship between its clinical efficacy and pharmacological actions. Recently zotepine has been reported to have an antimanic effect. The author also demonstrated our recent study on the antimanic drugs including zotepine and discussed the importance of the role of serotonin-2 receptor in their antimanic effect. PMID- 2883682 TI - Effectivity of zotepine in refractory psychoses: possible relationship between zotepine and non-dopamine psychosis. AB - We reported the results of a survey of patients who suffered from schizophrenia with predominate hallucinatory and delusional states, and who had been unresponsive to a variety of antipsychotics like haloperidol but responded more favorably to zotepine. In 10 of the 22 zotepine-responsive patients in this study, there was marked improvement with zotepine. Considering the results from previous drug treatment, the phenothiazines (especially levomepromazine) surpassed the butyrophenones in efficacy, suggesting that zotepine might resemble levomepromazine clinically. After administration of zotepine, cenesthesic hallucination, behavior caused by hallucination, egorrhoe, affective symptoms, and catatonic symptoms were markedly improved. However, insight into disease and negative symptoms were minimally improved after administration of zotepine. Zotepine was effective in the refractory psychoses due to its potent action on the delusional dynamics, in spite of producing little marked improvement in such main symptoms as hallucination and delusion. The authors speculate that zotepine's potent activity at serotonin-1 receptors may lead to a beneficial effect in refractory psychoses, just as in the case of its antimanic effect. PMID- 2883683 TI - Zotepine, a neuroleptic drug with a bipolar therapeutic profile. AB - Zotepine, a new tricyclic compound, was investigated in 20 schizophrenic patients in two different dosage groups. Group I (n = 8) received Zotepine in a high dosage of 270 mg +/- 37 mg/die. The other group (group II; n = 12) received a low dosage of 168 mg +/- 15 mg/die. In both groups 2 patients dropped out before the end of the treatment period because of clinical deterioration. In both groups, Zotepine manifested a rapid antipsychotic effect, good tolerability, and sedative properties during the initial days. Additionally there was a stronger positive influence on negative symptoms in the group with low dosage treatment. PMID- 2883686 TI - Results of an open phase II study with zotepine--a new neuroleptic compound. AB - Zotepine is a new tricyclic neuroleptic with a pharmacological profile comparable to substances such as thioridazine and chlorpromazine. Ten patients fulfilling DSM-III criteria of paranoid schizophrenia were included in an open pilot study at the Department of Psychiatry in Innsbruck. Neuroleptic efficacy, optimal dose, side effects, and the influence on serum prolactin levels were evaluated. Definite onset of antipsychotic action could be demonstrated between days 5-10, and approximately 400 mg/die seems to be an optimal dose. Four patients showed side effects of a minor degree that had no influence on the course of therapy. These results suggest that Zotepine is a rapidly acting neuroleptic with a high benefit-risk ratio. Further double-blind studies will be needed to reinforce these preliminary data. PMID- 2883685 TI - Low-dose zotepine in the maintenance treatment of schizophrenia. AB - Zotepine is new tricyclic neuroleptic with a pharmacological profile comparable to substances such as thioridazine and chlorpromazine. Its chemical structure is related to clozapine and fluperlapine. Ten patients (8 men and 2 women) fulfilling DSM III criteria for residual schizophrenia participated in an open clinical trial that lasted 8 months. The effects of low-dose maintenance therapy with Zotepine were evaluated using the Brief Psychiatric Rating Scale and the Scale for the Assessment of Negative Symptoms. Eight patients dropped out of the study within the first 6 months, 5 because of acute psychotic relapse, 3 due to compliance problems. Psychotic relapse appeared to be indicated by increasing BPRS and SANS scores recorded 1 month before relapse. Apart from minor sedation, no side effects, especially none of the extrapyramidal motor type, were observed. Even though Zotepine does not seem to possess sufficient prophylactic properties against psychotic relapse, preliminary results suggest that it might play an important role as a supplement to conventional neuroleptics in the near future. PMID- 2883687 TI - Clinical and EEG studies of zotepine, a thiepine neuroleptic, on schizophrenic patients. AB - The overall effect of zotepine was a "slightly improved" or better response in 20 patients (64.5%), "unchanged" in 10 (32.3%) and "worsened" in 1 (3.2%). Zotepine exhibited some degree of improvement in 54.5% of patients unresponsive to prior drugs. The onset of effect of zotepine was within one month in 19 patients. The improvement rate in the hebephrenic type (66.7%) was almost the same as in the paranoid type. The improvement rate classified by psychopathology was highest for hypobulia, followed by restlessness-excitement and hallucination, depressive mood, hypochondria and delusion. The side-effects were subjective complaints, such as general fatigue, dryness of mouth, sleepiness or fainting in a small number of cases. There was a slight increase in S-GPT in one patient and a slightly increased blood platelet count, also in one patient. Serial EEG changes associated with zotepine studied in another 17 chronic schizophrenics could be classified into three groups: those with increased slow waves, those with enhanced alpha waves and those with unchanged EEGs. There was a positive correlation between the incidence of slow waves and higher plasma levels of zotepine. PMID- 2883684 TI - Zotepine in the treatment of negative symptoms in chronic schizophrenia. AB - Zotepine is a new tricyclic neuroleptic with a pharmacological profile comparable to substances like Thioridazine and Chlorpromazine. In an open pilot study, 10 patients suffering from negative symptoms in the course of chronic schizophrenia were treated with Zotepine. The efficacy of Zotepine in this indication was evaluated by means of the BPRS and the Andreasen Scale for the Assessment of Negative Symptoms. Significant improvement could be demonstrated after 3 weeks of treatment. No side effects were observed within the dosage range of 50 to 200 mg per die. These results suggest that Zotepine is useful in the treatment of residual schizophrenia. PMID- 2883688 TI - An evaluation of the interactions between freshwater pulmonate snail hosts of human schistosomes and macrophytes. AB - An account is given of a laboratory investigation designed to evaluate the extent to which the freshwater pulmonate snail Biomphalaria glabrata (Say) can utilize various species of aquatic plants, mainly macrophytes, when presented in the following forms over different time scales: normal plants; dried plant material; homogenized plant material in calcium alginate matrices; water-soluble filtrates of plant homogenates in the medium. The following propositions, derived from the theory of phased coevolution of components of the module consisting of the epiphytic bacteria, algae, snails and macrophytes, are evaluated on the basis of the present results and others including those obtained in this laboratory. That as the snails had become specialized to exploit surface communities of epiphytic algae, decaying plant material and dissolved organic matter (DOM) early in their evolutionary history they would continue to exploit these resources when they later become associated with aquatic macrophytes. That pulmonate snails would tend to be feeding generalists capable of adapting to food of varying chemical composition, given sufficient time, provided it was sufficiently small or flaccid. That although macrophytes and snails show a strong positive relationship, the living macrophyte tissue would be little used by the snails. That the hard outer envelope, inherited from their terrestrial ancestors, would remain as the major defence mechanism of aquatic macrophytes against attack by snails and other aquatic invertebrates. That aquatic macrophytes would invest little in the nutrient deficiency strategy to reduce attack by invertebrates such as snails. That truly aquatic submerged macrophytes would not possess secondary plant compounds (SPC) that would be molluscicidal. Emergent parts of subaquatic or aquatic plants might be expected to be better sources of SPC with molluscicidal factors than submerged aquatic plants. Species of epiphytic or planktonic algae might be better sources of SPC with molluscicidal effects than aquatic macrophytes. That the strategies developed by pulmonate snails for obtaining their energy supplies would not be conducive to rapid speciation. The analysis of the present and other related results supports these propositions. Predictions based on the theory of mutualism involving the snails, macrophytes and other components of the module also receive some support from an analysis of the present results. The additional empirical work that could be undertaken to test this theory is briefly discussed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2883689 TI - [Acute vasculitis]. PMID- 2883690 TI - [Granulomatous vasculitis]. AB - Granulomatous vasculitis are defined as a pathological process due to the destruction of vessels by a granulomatous infiltrate. The inflammatory infiltrate is made of several cellular lines in variable proportions. These diseases are classified according to the affected organs and to the nature of the vessels. Some granulomatous vasculitis remain cryptogenetic in nature, others have an infectious origin, and still others follow a necrotizing leucocytoclastic vasculitis with immune complexes. PMID- 2883691 TI - Changes in neurotransmitter amino acids content in several CNS areas from aggressive and non-aggressive bull strains. AB - Neurotransmitter amino acid levels (glutamate, aspartate, GABA, and glycine) of crude synaptosomal fractions from several non-limbic CNS areas (pons, ventral tegmentum, midbrain reticular formation, fastigial nucleus of cerebellum, posterior colliculus and anterior colliculus) showed significant differences between aggressive Spanish fighting-bull and non-aggressive Friesian strains. The most unequal distribution was observed in neurotransmitter amino acids, while the non-transmitter amino acids (serine, isoleucine, leucine, threonine and alanine) showed minor and uneven changes. The results suggest a possible relationship between changes in amino acid neurotransmitter levels and the aggressive behavior observed in the aggressive breed. PMID- 2883692 TI - [Blood levels of neuroleptics required to prevent recurrence--a radioreceptor assay]. PMID- 2883693 TI - [The safety of long-term neuroleptic therapy]. PMID- 2883694 TI - Psychotic and nonpsychotic depressions: I. Comparison of plasma catecholamines and cortisol measures. AB - Unconjugated plasma catecholamines and cortisol were measured before and after a 1 mg dose of dexamethasone in 22 medication-free depressed patients and 6 healthy, medication-free control subjects. Plasma dopamine (DA) levels in the psychotically depressed subgroup (n = 4) were significantly higher both before and after dexamethasone than those in the nonpsychotic depressed group and higher before dexamethasone than in the control group. Similarly, the psychotically depressed group exhibited significantly higher cortisol levels both before and after dexamethasone than the nonpsychotic depressed group or the control group. In contrast, the psychotically depressed group had significantly lower postdexamethasone plasma norepinephrine levels compared to the nonpsychotic depressed group. In both patients and controls, plasma DA was significantly higher after dexamethasone administration than before, but the magnitude of the increase was 10 times greater in controls than in patients. PMID- 2883695 TI - Benzodiazepine pharmacodynamics: evidence for biophase rate limiting mechanisms. AB - Pharmacokinetics do not adequately reflect recovery from cognitive neuromotor impairment induced by most benzodiazepines. This paper examines across time the nature of the relationship of effect to serum concentration of three benzodiazepines. Using the same protocol lorazepam, alprazolam, diazepam and placebo were administered to eight healthy males at doses of 0.057, 0.029, 0.286 and 0.000 mg/kg, body weight, respectively for the first study and at 0.028, 0.014, 0.143 and 0.000 mg/kg, respectively, for the second study. After each dose administration multiple measurements were made over a period of 5.5-11.5 h using two different psychomotor performance tests. Serum drug concentrations were also measured. The profiles for diazepam and alprazolam effects demonstrate a stepwise decrement in the slopes of the concentration versus response curves across time, illustrating the rapid development of acute tolerance. In contrast, lorazepam induced a remarkably constant relationship between concentration and effect across testing intervals. PMID- 2883698 TI - Benzodiazepine--induced event amnesia following a stressful surgical procedure. AB - In a randomised, double-blind, parallel groups study, 40 patients undergoing surgical removal of impacted third molar teeth received either midazolam 15 mg orally followed at 35 min by intravenous saline or oral placebo followed by intravenous diazepam 10 mg (Diazemuls). Episodic (event) memory was assessed by showing patients photographs of dental and neutral objects both before and after sedation and by testing subsequent recognition at 1 week. Recall of actual surgical events was assessed by questionnaire. Both treatments induced significant amnesia for visual stimuli and for surgical events. However, the degree of amnesia was more profound for artificial stimuli and no relationship was found between the extent of amnesia for the two types of event. Drilling of bone was found to provoke the greatest cardiovascular stress response and a significant relationship was found between the degree of cardiovascular activation and subsequent memory for drilling. It is concluded that the extent of benzodiazepine-induced event-amnesia may be modified by cognitive factors and especially by the extent to which the event is cognitively encoded and elaborated. PMID- 2883697 TI - Cytotoxic effects of neuroleptic drugs. AB - Agranulocytosis and the release of transaminase enzymes from liver cells are known consequences of neuroleptic drug use. These effects are most common with low potency neuroleptic drugs. It has been hypothesized that these effects are due to the direct toxic action of these drugs on blood and liver cells. The purpose of this study is to compare the cytotoxic effects of eight neuroleptic drugs in five different biological test systems. In all of the test systems, thioridazine, chlorpromazine, trifluoperazine, fluphenazine and thiothixene (group one drugs) were the most toxic drugs and molindone was the least toxic. Thioridazine was between 25 and 84 times more toxic than molindone. Loxapine was significantly more toxic than molindone, but less toxic than the group one drugs. Haloperidol was intermediate in toxicity between the group one drugs and loxapine. We conclude that the difference in cytotoxicity of the neuroleptic drugs observed in these experiments accounts in part for the increase in agranulocytosis and hepatotoxicity with thioridazine and chlorpromazine and for the lower incidence of these side effects with less toxic drugs. The possibility that tardive dyskinesia may be due to the cytotoxic effects of neuroleptic drugs is discussed and an experiment to test this hypothesis is suggested. PMID- 2883696 TI - Effect of antidepressant and neuroleptic drugs on the electrically evoked release of serotonin from rat cerebral cortex. AB - The effect of antidepressant and neuroleptic drugs on the electrically evoked release of serotonin (5-HT) was investigated in rat brain cortical slices preincubated with 0.1 mumol/l 3H-5-HT. Zimelidine, trazodone, clomipramine, doxepin, and viloxazine (1 mumol/l each) enhanced the electrically-induced 3H overflow by 20-44%. Six other antidepressants and five neuroleptics did not increase the evoked transmitter release. Only trazodone and viloxazine also increased the 3H overflow in experiments in which neuronal 5-HT reuptake was already blocked by 6-nitroquipazine. 5-HT and clonidine inhibited the electrically-induced 3H-5-HT release by stimulation of presynaptic 5-HT autoreceptors and alpha 2-adrenoceptors, respectively; trazodone and viloxazine had no effect on the concentration-response curves of 5-HT and clonidine. Other psychotropic agents with well known antiserotonergic activities also failed to block presynaptic 5-HT autoreceptors. It is concluded that zimelidine, clomipramine, and doxepin enhanced the 3H-5-HT overflow by inhibition of neuronal 5-HT uptake, whereas the increase produced by trazodone and viloxazine cannot be explained by reuptake inhibition or interaction with presynaptic receptors. PMID- 2883699 TI - Treatment for therapy-resistant depression. AB - Thanks to progress in the diagnosis and treatment of depression it is now possible for most cases to be treated on an out-patient basis. Only 15-20% of patients require hospitalisation, most of them because their depression has proved resistant to therapy. To overcome therapy-resistance, the following methods of treatment are available: In therapy-resistant endogenous and psychogenic depressions, mono-infusion therapy is the treatment of choice; it can also be administered on an out-patient basis. In extremely intractable cases, it is advisable to resort to combined infusion therapy, preceded by five days of relaxation therapy with oral doses of a neuroleptic, and possibly reinforced by medication with 5-hydroxytryptophan (the precursor of serotonin) or by sleep deprival. In therapy-resistant cases of so-called masked depression, marked by overtones of anxiety and hypochondriasis, infusions of maprotiline are indicated, because this anti-depressant exerts a relaxing and mildly anxiolytic action, has a stabilising influence on the autonomic nervous system, and produces a mood brightening effect. In patients who are apathetic and devoid of drive and suffering from involutional depression or depression of old age, infusion therapy plus administration of an MAO inhibitor can be recommended. Combination of an antidepressant with a neuroleptic agent also displaying certain antidepressive properties is really indicated only in the rare cases of schizo-affective psychosis. Electroconvulsive therapy should be employed only as a last resort in extremely retarded and apathetic patients with strong suicidal tendencies, and the indication for ECT should be established with the utmost reserve. PMID- 2883700 TI - Biological aspects of depression in Parkinson's disease. AB - A clinical survey indicates a similar incidence of depression in old age and Parkinson's disease. Divergences, therefore, are apparent, when the biochemical basis of depression is related to the pathobiology of Parkinson's disease (PD) and endogenous depression. However, a common biological concept for endogenous depression and depression in PD is possible by assuming that neurotransmission can operate at various levels of homeostasis. Then depression is the behavioral correlate rather of regional changes that disturb this homeostasis. Therefore, the incidence of depression in old age and PD is similar. PMID- 2883701 TI - Monoamines and myelin components in aging and dementia disorders. PMID- 2883702 TI - Neuropeptide changes in aging and Alzheimer's disease. PMID- 2883703 TI - Aging and circadian rhythms. PMID- 2883704 TI - Clinical strategies in the treatment of Alzheimer's disease. PMID- 2883705 TI - Possible dietary strategies to reduce cognitive deficits in old age. PMID- 2883706 TI - The physiology of excitatory amino acids in the vertebrate central nervous system. PMID- 2883707 TI - Amino acids and hepatic encephalopathy. AB - The consideration of HE and its etiology has undergone a radical turn within the past decade. At present HE is seen in the context of severe metabolic derangements, which failure of the liver, the central biochemical powerhouse of the body, must bring with it. The increased awarenesses on the biochemical mechanisms involved in the pathogenesis of HE have found, step by step, their own place in a complex but consequential mosaic of events, in which amino acid and HE are tightly linked. Clinical and experimental studies are needed to further improve the knowledge in this field, nontheless a certain number of corner-stones can be identified: A profound alteration of the central nervous system neurotransmission is responsible for most, if not all, of the symptoms characterizing HE. The plasma amino acid imbalance observed in cirrhotic patients represents a 'condicio sine qua non' HE may develop. A functional impairment of the amino acid transport systems at the level of the blood-brain barrier seems to play a crucial role in causing deleterious modifications of the synaptic neurotransmission in the central nervous system. The reduction of the brain entry of the "toxic" aromatic amino acids usually obtained by parenteral administration of especially tailored amino acid mixtures is most frequently followed by awakening from HE. In conclusion, most of the results obtained have demonstrated that HE represents a research field in which progresses in the knowledge of some of the pathogenic mechanisms have brought the investigators to new therapeutic approaches which have clearly improved the prognosis of patients suffering from this severe neuropsychiatric syndrome. PMID- 2883708 TI - Bradykinin receptors: functional similarities in guinea pig gut muscle and mucosa. AB - It is well established that bradykinin can stimulate mucosal electrolyte transport. However, the receptor type which mediates this effect has not been fully characterized. Recent studies have suggested that bradykinin and related kinins may act at two types of receptors designated as B1 and B2. We have determined the effect of bradykinin on electrolyte secretion across guinea pig ileal mucosa and longitudinal muscle in vitro in the presence and absence of D Phe7-bradykinin (B2 antagonist) and des-Arg9-(Leu8)-bradykinin (B1 antagonist). The B2 antagonist (less than 100 microM) did not affect resting muscle tension or basal electrolyte transport but at 6-30 microM it caused a parallel rightward shift in the concentration-response curves to bradykinin in the mucosa (Ki = 4 microM) and muscle (Ki = 6 microM). Changes in electrolyte transport and muscle contractility evoked by bethanechol and substance P were not affected by the B2 antagonist (30 microM) in either the muscle or the mucosa. Moreover, changes in electrolyte transport and muscle contractility produced by bradykinin were not altered by the B1 antagonist (30 microM). Finally, the B1 agonist des-Arg9 bradykinin (10 nM-1 microM) was not active in either preparation. These data suggest that under normal conditions, ileal secretion and smooth muscle contractility in the guinea pig are regulated by B2-type bradykinin receptors. PMID- 2883709 TI - [Clostridium perfringens septicotoxemia]. PMID- 2883710 TI - Retinal vasculitis in polyarteritis nodosa. AB - Although uncommon, a wide variety of ocular manifestations can be seen in polyarteritis nodosa. These occur as a result of the arteritis or secondary to the associated renal induced hypertension. A case of biopsy documented polyarteritis nodosa is reported in which the patient presented with bilateral iritis, vitritis, and a retinal vasculitis involving both the retinal arteries and veins, a feature not described previously. Patients with this potentially fatal disorder may initially present with ocular involvement; thus ophthalmologists should be familiar with the clinical features of this disease. PMID- 2883711 TI - [Cardiogenic shock in acute myocardial infarction]. PMID- 2883712 TI - [Proper usage of H1-antihistaminics]. PMID- 2883714 TI - Traumatic injuries of the teeth. PMID- 2883713 TI - [Original construction of a device for the dento-maxillary protection]. PMID- 2883715 TI - Treatment of seasonal allergic rhinitis--a double blind, group comparative study of terfenadine and dexchlorpheniramine. AB - In order to evaluate the efficacy of and adverse reactions to terfenadine compared to dexchlorpheniramine, a double blind, group comparative study was carried out in 42 patients suffering from grass-pollen induced allergic rhinitis. The treatment was either terfenadine tablets 60 mg twice daily or dexchlorpheniramine tablets 6 mg twice daily. Nasal and eye symptoms as well as tiredness were rated daily on a scale from 0 (absent) to 3 (severe). Terfenadine and dexchlorpheniramine performed almost equally well in keeping symptoms at a mild level with a superiority of dexchlorpheniramine in the control of runny nose. Dexchlorpheniramine was associated with a significant increase in the score for tiredness in contrast to terfenadine which caused no significant change. Two patients in the group treated with dexchlorpheniramine stopped treatment because of tiredness. Other adverse reactions were few, mild and transient. PMID- 2883716 TI - [Clinical evaluation of clotiazepam in the ambulatory treatment of anxiety states]. AB - To assess the therapeutic efficacy and tolerability of Clotiazepam in the treatment of anxiety, the drug was administered to 20 subjects suffering from anxiety (12 cases) or from nervous depression (8 cases), all of whom were without psychopharmacological drugs for at least one month prior to the trial. Treatment with Clotiazepam improved the anxiety and brought about a statistically significant reduction in both groups of patients regards the total score in the Hamilton Scale and in the two sub-scale scores (somatic and psychological symptoms). Tolerability to the drug was very satisfactory. PMID- 2883717 TI - [3 cases of essential blepharospasm: pathogenetic problems correlated]. AB - Three clinical cases of essential blepharospasm are discussed. On the basis of both therapeutical results and a review of the literature, pathogenetic hypothesis concerning such pathology are reexamined. PMID- 2883718 TI - The variations of S-adenosyl-L-methionine content modulate hepatocyte growth during phenobarbital promotion of diethylnitrosamine-induced rat liver carcinogenesis. AB - A decrease in liver S-adenosyl-L-methionine (SAM) content and an increase in ornithine decarboxylase (ODC) activity occurred between the 2nd and the 5th week after starting 2-acetylaminofluorene (AAF) feeding in diethylnitrosamine (DENA) initiated rats. These rats then received a 0.05% phenobarbital (PB)-containing diet for 18 weeks after the end of AAF feeding. Two weeks after starting AAF, an increase in the hepatocyte labeling index (LI) also occurred in gamma-glutamyl transpeptidase (GGT)-positive foci and surrounding tissue. LI returned to control values in a few days in surrounding tissue, while it remained high for at least 4 weeks in the foci. Analogous changes were observed, but for a shorter period of time, in the rats subjected to partial hepatectomy (PH) plus AAF, in which no GGT positive foci developed. Twenty-four weeks after starting AAF, 30% of the liver was occupied by visible nodules. ODC activity and LI were high and SAM was low in nodules, but they were near to control values in surrounding liver. SAM administration reconstituted the liver SAM pool, inhibited ODC activity, and prevented visible nodule development. SAM inhibition of ODC activity occurred in vitro only after preincubation with liver homogenate and was enhanced by adenine, an inhibitor of methylthioadenosine (MTA) phosphorylase. MTA addition to the reaction of mixture for ODC determination was inhibitory. The SAM decrease in both liver and nodules was coupled with a decrease of MTA content. SAM administration caused MTA accumulation in the liver. It is suggested that liver SAM content by influencing MTA level, could be a rate-limiting factor for growth and promotion, through a modulation of polyamine synthesis. PMID- 2883720 TI - Morphotypic aspects in the cryptorchidic child. AB - The morphotype of 40 children with cryptorchidism (18 bilateral, 22 unilateral), selected by complex endocrine examination, was assessed in relation to age and clinical form of cryptorchidism. The morphotype was established on the basis of 9 anthropometric parameters (weight, stature, pube-ground distance, a-a, thr-thr, thoracic, abdominal, hips and cephalic circumferences). The malformed lot consists of 28 children with common and 12 with symptome cryptorchidism (5 adiposogenital, 3 male Turner's syndrome and 3 with gonadal dysgenesis). In the child with symptom cryptorchidism, the morphogram reveals, irrespective of age, a morphotype which corresponds in point of absolute dimensions and proportions, to the somatotype in which cryptorchidism as a symptome is included. The child with common cryptorchidism has irrespective of age, a normal or short stature and is underweight. Compared to the stature, the head is small, the lower limbs are short, the trunk is long and the hips are well developed. In our series of common cryptorchid child, the most marked statural deficit was found between 11 and 15 years as well as under the age of 6. PMID- 2883719 TI - Placental glutathione S-transferase (GST-P) as a new marker for hepatocarcinogenesis: in vivo short-term screening for hepatocarcinogens. AB - Our laboratory has developed an in vivo short-term screening test for hepatocarcinogens based on quantitation of gamma-glutamyl transpeptidase (gamma GT) positive foci. However, gamma-GT positive hepatocytes appear in periportal areas under a variety of circumstances apparently unrelated to hepatocarcinogenesis. Glutathione S-transferase placental type (GST-P), which is hardly detectable in normal rat liver, was recently demonstrated as a new marker protein for preneoplastic liver foci. In experiment I, rats were initially given a single dose (200 mg/kg) of diethylnitrosamine intraperitoneally and 2 weeks later were treated with test compounds for 6 weeks. All rats were subjected to partial hepatectomy at week 3. The long-term development of preneoplastic lesions was followed in rats for 50 weeks. The immunohistochemical investigation of GST-P binding and the histochemical demonstration of gamma-GT in serial sections revealed that almost all gamma-GT foci were GST-P positive, but 5-10% of GST-P foci could not be detected by gamma-GT staining. From week 8, many gamma-GT foci partially lost gamma-GT activity. However, no comparable disappearance of GST-P was evident in the lesions. All hepatocellular carcinomas (HC) found at week 50 consisted of GST-P positive HC cells. In contrast, 37.9% (11/29) of HC were negative for gamma-GT. In experiment II (in vivo short-term screening test for hepatocarcinogens), rats were treated in the same manner as for experiment I and killed at week 8. Fifty-eight chemicals were investigated for their potential to modify GST-P positive foci development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883721 TI - The neuro-transmitters of the efferent cochlear system. PMID- 2883722 TI - Pharmacological effects on cochlear blood flow measured with the Laser-Doppler technique. PMID- 2883723 TI - Asymptomatic peptic ulcer disease. PMID- 2883724 TI - Reflex sympathetic inhibition of colonic motility in the cat. AB - Sympathico-adrenergic mechanisms involved in the reflex inhibition of colonic motility were investigated in anaesthetized cats. Reflex inhibition of spontaneous motility of the colon was induced by application of hydrochloric acid onto the serosal surface of the small intestine and the peritoneum of the abdominal wall. This inhibition was reduced by propranolol and phentolamine. The spontaneous colonic motility was also reduced by administration of isoproterenol, noradrenaline, and clonidine. It is concluded that the sympathetic reflex inhibition of colonic motility is mediated by alpha- and beta-adrenergic mechanisms in the cat. PMID- 2883725 TI - Somatostatin inhibition of intrinsic factor secretion from isolated guinea pig gastric glands. AB - The aim of our study was to examine the direct effect of somatostatin on histamine- and pentagastrin-stimulated intrinsic factor (IF) release in collagenase-dispersed guinea pig gastric glands. The effect of somatostatin (10( 11) M to 10(-6) M) on half-maximal doses of histamine (10(-6) M), pentagastrin (10(-6) M), and both histamine and pentagastrin together was tested. All tested concentrations of histamine significantly stimulated IF release. Pentagastrin (10(-10) M to 10(-6) M) inconsistently stimulated IF release. The quantity of IF release stimulated by histamine and pentagastrin together was approximately the additive sum of that produced by either agent alone. Somatostatin (10(-6) M) inhibited histamine-stimulated (10(-6) M) IF release by 69.9 +/- 7.2% and the combination of histamine (10(-6) M) and pentagastrin (10(-6) M) by 64.2 +/- 9.1%. This is the first in vitro demonstration that somatostatin inhibits IF release. PMID- 2883726 TI - Different effects of enantiomers of tetrahydropalmatine on dopaminergic system. AB - Tetrahydropalmatine (THP) has two enantiomers with different effects on the brain dopaminergic system. Using [3H]spiperone for DA receptor binding assay, it was found that l-THP had an affinity to DA receptors (Ki = 0.2 microM). Neither d-THP nor reserpine showed such an effect even at concentrations higher than 100 or 1000 microM. Based on the fact that the presynaptic DA receptors take part in feed-back regulation on tyrosine hydroxylase activity, DOPA accumulation could be observed in rat striatum after injection of benserazide. A small dose of l-THP (2.5, 5, 10 mg/kg, ip.) caused an elevation of DOPA level by 49-282% versus the control value, and could reverse the decrease of DOPA level induced by apomorphine, a DA receptor agonist. On the contrary, d-THP displayed a biphasic effect on DOPA level, slight decrement (26-37%) at 10 and 25 mg/kg, naught at 50 mg/kg, and a 91% increment at 100 mk/kg, which was less than that of l-THP at 5 mg/kg. Moreover, measured by pulse voltammetry, DOPAC level in the striatum was raised by 88 or 190% at 2.5 or 10 mg/kg respectively. By means of spectrofluophotometry, l-THP at 50-100 mg/kg reduced DA level by 24-26%. However, the DA content reduction induced by d-THP is much more dose-dependent. At a small dose (10 mg/kg), d-THP predominantly reduced the DA level but left 5-HT and NA level unaffected. It caused an 80% reduction of DA at 100 mg/kg. From the above findings, it might be concluded that l-THP is a DA receptor antagonist, while d THP is probably a DA depletor. PMID- 2883727 TI - Assembly of clathrin-coated pits onto purified plasma membranes. AB - During receptor-mediated endocytosis, coated pits invaginate to form coated vesicles, clathrin and associated proteins dissociate from the vesicle membrane, and these proteins form new coated pits at the cell surface. As a means of elucidating molecular mechanisms that govern the function of coated pits, the assembly phase of this cycle was reconstituted by incubating purified membranes that were treated to remove endogenous coated pits with cytoplasm extracted from cultured cells. The in vitro assembly of coated pits on these membranes satisfactorily mimics many features of coated pit formation in the intact cell. These studies indicate that: the membranes contain a limited number of coated pit assembly sites that bind clathrin with high affinity; the half-time for assembly is 5 minutes both at 4 degrees C and 37 degrees C; during assembly, proteins with molecular sizes of 180, 110, and 36 kilodaltons are recruited to the plasma membrane; and assembly is not dependent on adenosine triphosphate, but this nucleotide triggers a temperature-dependent loss of coated pits that are assembled in the absence of adenosine triphosphate. PMID- 2883728 TI - Zinc selectively blocks the action of N-methyl-D-aspartate on cortical neurons. AB - Large amounts of zinc are present in synaptic vesicles of mammalian central excitatory boutons and may be released during synaptic activity, but the functional significance of the metal for excitatory neurotransmission is currently unknown. Zinc (10 to 1000 micromolar) was found to have little intrinsic membrane effect on cortical neurons, but invariably produced a zinc concentration-dependent, rapid-onset, reversible, and selective attenuation of the membrane responses to N-methyl-D-aspartate, homocysteate, or quinolinate. In contrast, zinc generally potentiated the membrane responses to quisqualate or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and often did not affect the response to kainate. Zinc also attenuated N-methyl-D-aspartate receptor-mediated neurotoxicity but not quisqualate or kainate neurotoxicity. The ability of zinc to specifically modulate postsynaptic neuronal responses to excitatory amino acid transmitters, reducing N-methyl-to-aspartate receptor-mediated excitation while often increasing quisqualate receptor-mediated excitation, is proposed to underlie its normal function at central excitatory synapses and furthermore could be relevant to neuronal cell loss in certain disease states. PMID- 2883730 TI - Leukemia virus linked to nerve disease. PMID- 2883729 TI - Identification of a T3-associated gamma delta T cell receptor on Thy-1+ dendritic epidermal Cell lines. AB - The murine epidermis contains a subpopulation of bone marrow-derived lymphocytes that have a dendritic morphology and that express Thy-1 and T3 cell-surface antigens but not other markers (L3T4 or Lyt-2) characteristic of mature peripheral T lymphocytes. An alternative type of T cell receptor was earlier identified on a subpopulation of murine thymocytes with a similar phenotype (T3+, L3T4-, Lyt-2-), but not on peripheral murine T lymphocytes. Two independently derived Thy-1+, L3T4-, and Lyt-2- dendritic cell lines of epidermal origin that express a T3-associated disulfide-linked heterodimer composed of a 34-kilodalton gamma-chain and 46-kilodalton partner (the delta chain) have now been identified. Analysis of N-linked glycosylation revealed that this receptor is similar to that detected on thymocytes. These results demonstrate that Thy-1+ dendritic epidermal cell lines can express gamma delta T cell receptors in vitro and suggest that Thy 1+ dendritic epidermal cells express such receptors in vivo. The localization of these gamma delta T cell receptor-expressing cells in the epidermis may be of importance for understanding the function of these receptors. PMID- 2883732 TI - In vitro studies on the sensitivity of local Entamoeba histolytica to anti amoebic drugs. AB - The in vitro activity of drugs, namely dehydroemetine, ornidazole, metronidazole and tinidazole were determined against the locally isolated strains of E. histolytica in Thailand. The test was performed in liquid monophasic medium, i.e. liver marmite serum medium. In all, locally isolated strains from thirty hosts studied, the minimal inhibitory concentration (MIC) for dehydroemetine ranged from 0.125 to 1 microgram/ml, ornidazole ranged from 0.0625 to 0.25 microgram/ml, metronidazole ranged from 0.0625 to 0.125 microgram/ml, and tinidazole ranged from 0.0625 microgram/ml to 0.25 microgram/ml. The MIC of dehydroemetine was significantly different from ornidazole, metronidazole and tinidazole. Metronidazole was superior to that of dehydroemetine but was not significantly different among ornidazole, metronidazole and tinidazole. PMID- 2883731 TI - HTLV-I--associated B-cell CLL: indirect role for retrovirus in leukemogenesis. AB - Serum containing antibodies to the human T-lymphotropic virus type I (HTLV-I) has been observed at a higher than expected frequency in patients with B-cell chronic lymphocytic leukemia (CLL) in an area endemic for HTLV-I. An attempt was made to determine whether the cells from patients with this leukemia were HTLV-I antigen committed B cells that had undergone malignant transformation. Cells from two HTLV-I seropositive Jamaican patients with CLL were fused with a human B lymphoblastoid cell line. The hybridoma cells that resulted from the fusion of CLL cells from patient I.C. produced an immunoglobulin (IgM) that reacted with the p24 gag protein from HTLV-I, HTLV-II, and HTLV-III (now referred to as HIV), but showed preferential reactivity with HTLV-I. The specific immunoglobulin gene rearrangement (IgM, kappa) in the CLL cell was demonstrated in the hybridoma cell line, indicating that the captured immunoglobulin was from the CLL cells. The IgM secreted by the fusion of CLL cells from patient L.L. reacted only with HTLV-I infected cells and with the HTLV-I large envelope protein (gp61) on Western blots. The CLL cells from these patients appear to be a malignant transformation of an antigen-committed B cell responding to HTLV-I infection, suggesting an indirect role for this retrovirus in leukemogenesis. PMID- 2883733 TI - [Pleuropulmonary complications caused by beta blockaders]. PMID- 2883735 TI - [Problems caused by beta-2 sympathomimetic aerosols]. PMID- 2883734 TI - [Bronchopulmonary complications of antirheumatic drugs]. PMID- 2883737 TI - [Detection of anxiolytic effects of suriclone on stress induced by dental surgery]. PMID- 2883736 TI - [Effects on memory and psychomotor performance induced in healthy subjects by 3 hypnotic benzodiazepines (triazolam, flunitrazepam, loprazolam)]. PMID- 2883738 TI - [Beta-sympathicomimetics in premature labor. Effects on the fetus]. PMID- 2883739 TI - gamma-Glutamyltransferase activity in atypical acinar cell nodules of rat pancreas. AB - The biochemical and histochemical measurement of the enzyme gamma glutamyltransferase (GGT) was undertaken in normal rat pancreas and in rat pancreas containing azaserine-induced preneoplastic nodules. A steady decrease in pancreatic GGT activity was observed in the normal animals as they aged from 5 to 34 weeks. The azaserine-induced nodules contained a lower average GGT activity than the control pancreas although a 10-fold variation was noted in the GGT activity of individual nodules. A significant increase in concentrations of both reduced glutathione and oxidized glutathione was noted in pancreatic nodules from azaserine-treated rats compared to concentrations found in both control pancreas from untreated rats and internodular pancreas from azaserine-treated rats. A pancreatic acinar cell carcinoma contained low GGT activity--similar to that found in large nodules and about 10% of the level found in control pancreas. Pancreatic GGT levels were higher in 5- and 7-week-old rats fed chow than in rats fed a purified diet, but this effect of chow was not observed at 34 weeks of age. Feeding a purified diet supplemented with a retinoid, N-2-hydroxyethylretinamide (2-HER), for a period of 2 weeks did not influence the GGT activity level in either normal pancreas or in the azaserine-induced nodules. While decreased GGT activity does not serve as a marker for all atypical acinar cell nodules, deficient activity with concomitant increased glutathione levels appears to correlate generally with increased growth potential. PMID- 2883740 TI - Amino acid sequence of two sea anemone toxins from Anthopleura fuscoviridis. AB - The amino acid sequences of two toxins, AFT-I and AFT-II, from the sea anemone Anthopleura fuscoviridis were determined. AFT-I and -II consist of 47 and 48 amino acid residues, respectively, and are cross-linked with three disulfide bridges. The sequences have high homology to those of toxins I and II from Anemonia sulcata and anthopleurin-A and -B from Anthopleura xanthogrammica. PMID- 2883741 TI - Further observations on the tooth mutilating practices of Vassekela and !Kung Bushmen. PMID- 2883742 TI - [Comparative hygienic evaluation of apparatus intended for denture soldering]. PMID- 2883743 TI - Development of Thy 1 positive rat thymocytes: analysis of fetal and neonatal thymocytes by flow microfluorometry. AB - Rat thymocytes of embryos and neonates were analyzed for cell size and amount of Thy 1 by flow microfluorometry. The rat embryonic thymus of 18 days' gestation appeared to be composed of very large cells with relatively low levels of Thy 1. The Thy 1 content was intermediate between rat bone marrow cells (low Thy 1) and the majority of rat adult thymocytes (high Thy 1). As cells became small at the 19th and the 20th day, the Thy 1 content appeared to increase. In the early postnatal thymus of the rat large cells appeared with low Thy 1 levels which were comparable to those in the 18th day fetal thymus. These results indicate that immature thymocytes increase in Thy 1 content as they differentiate into more mature cells from low Thy 1 thymocyte precursors. This conclusion is in close agreement with our recent results regarding rat bone marrow prethymic lymphocyte progenitors and the rat immature thymocytes. PMID- 2883744 TI - Implantation of thymic epithelial grafts into the anterior chamber of the murine eye: an experimental model for analyzing T-cell ontogeny. AB - The object of this investigation was to establish whether the intracameral implantation of thymic epithelial grafts could be utilized as a valid in vivo experimental model for probing the possible mechanisms whereby the sympathetic innervation of the thymus influences thymocyte dynamics. Our findings suggest that deoxyguanosine-treated thymic epithelial grafts, implanted into the anterior chamber of the eye, were receptive to host lymphoid progenitor cells, capable of supporting T-lymphocyte maturational processes, and were able to export mature T cells to the secondary lymphoid organs of a previously T-cell deficient host. In addition, we verified that the number of lymphoid cells recovered from a thymic epithelial graft which had been implanted into an anterior chamber devoid of sympathetic nerve input was generally greater than the number of lymphoid cells recovered from a matched graft which had been implanted into an anterior chamber which had an intact sympathetic nerve supply. Based on the results of these studies, investigative efforts can now be directed at studying a number of important aspects associated with the relationship between T lymphocyte ontogeny and the sympathetic nervous system. PMID- 2883745 TI - Engraftment following T-cell-depleted marrow transplantation. I. The role of major and minor histocompatibility barriers. AB - These experiments describe a murine model for survival and engraftment of bone marrow transplantation across differing histocompatibility barriers. Anti-Thy-1.2 antibody and complement-treated C57BL/6 (B6) marrow was transplanted at varying cell dose levels into syngeneic (B6), major histocompatibility complex congenic (A.BY), semiallogeneic (B6AF1), and fully allogeneic (A/J) recipients. Survival was monitored and engraftment determined by hemoglobin and lymphocyte phenotype. Survival was cell-dose dependent and was equivalent in B6, A.BY, and B6AF1 recipients. Survival was poor in allogeneic A/J recipients due to bone marrow failure even at high marrow dose levels. Survival posttransplant did not always correlate with stable donor engraftment, and competitive host marrow repopulation was frequently seen in B6AF1 recipients but rarely in A.BY recipients. This repopulation could be prevented by transplanting a larger marrow dose. PMID- 2883746 TI - Observations on the seeding of hematopoietic stem cells. Selective development in the transplanted recipient. PMID- 2883747 TI - Administration of somatostatin analog (SMS 201-995) in the treatment of a fistula occurring after pancreas transplantation. Interference with cyclosporine immunosuppression. PMID- 2883748 TI - [Drug treatment of bleeding peptic ulcers]. PMID- 2883749 TI - [Acute protracted dystonia]. PMID- 2883750 TI - Pharmacologic treatment of impotence. AB - A discussion of the anatomy, neurophysiology, endocrinology, and organ pharmacology pertinent to erectile function is presented, highlighting recent innovations in the pharmacologic treatment of impotence. Both oral and intracorporal pharmacologic agents that affect erectile dysfunction are discussed. PMID- 2883751 TI - Pain control for the urologist. AB - Pain states can be divided into three categories: acute, chronic not resulting from malignancy, and chronic malignant pain. A Pain Clinic can provide in-depth evaluation and treatment of difficult pain problems. A variety of oral and parenteral medications, ranging from nonsteroidal analgesics to narcotics, are available to control pain. Local anesthetics can be used for local infiltration, and peripheral and central nerve blocks can also be used as indications warrant. PMID- 2883752 TI - [Painless extra-corporal shock wave lithotripsy using the HM3 Dornier lithotripter]. AB - In a clinical study with a modified shock wave generator supplied by Dornier Medizintechnik for the Dornier Kidney Lithotripter HM3 the requirement of analgetics decreased significantly during Opioid-Analgesia. It could be shown that Extra-corporal Shock Wave Lithotripsy is possible without a central acting drug. Furthermore, a reduction of perioperative morbidity could be observed with the new generator. PMID- 2883753 TI - Immunocytochemistry of normal pancreatic islets and spontaneous islet cell tumors in dogs. AB - Immunocytochemical studies of the distribution of glucagon, gastrin, insulin, and somatostatin in normal canine pancreatic islets and 20 canine islet cell tumors were done using the peroxidase-anti-peroxidase (PAP) technique. In the normal adult canine pancreas, islets typically consisted of clusters of 20-30 cells, but smaller foci and even individual cells were identified. Alpha cells (glucagon) were often peripherally located, beta cells (insulin) were centrally located and most numerous, and delta cells (somatostatin) were the least numerous and randomly located. Both juvenile and adult canine pancreases did not stain for gastrin. Of the 20 tumors examined, 18 had positive immunoreactivity for insulin, nine for glucagon, 14 for somatostatin, and one for gastrin. Two tumors were uninterpretable due to autolysis. Three tumors were pure insulinomas, but no pure somatostatinomas, glucagonomas, or gastrinomas were identified. Most tumors and metastases had mixed positive immunoreactivity; one neoplastic cell type predominated with lesser numbers of other cell types. Metastatic sites (liver and lymph node) stained for insulin and somatostatin, only. Foci of non-neoplastic islet cell tissue (nesidioblastosis), often located at the pancreatic-mesenteric junction, stained strongly positive for insulin, glucagon, and somatostatin but not for gastrin. The tumor staining pattern did not consistently correlate with tumor function, as determined by blood glucose and serum insulin assays. The PAP technique works well on paraffin-embedded, formalin-fixed tissue using rabbit or guinea pig antisera as the primary antibody. Staining occurred on sections of paraffin blocks stored for up to 7 years. PMID- 2883754 TI - Autoradiographic study of 3H-lysine uptake by superior cervical and stellate ganglia in prehypertensive spontaneously hypertensive rats. AB - In order to compare the functional state of sympathetic ganglia in spontaneously hypertensive (SHR) with those in normotensive Wistar Kyoto rats (WKY), protein synthetic activity was examined by light microscopic autoradiography with 3H lysine. The number of silver grains over the cytoplasm of ganglion cells in the superior cervical and stellate ganglia of newborn and 30-day-old animals were counted on photographic enlargements. In both sympathetic ganglia there were significantly more silver grains over ganglion cells in SHR compared with age matched WKY at 15, 60, and 120 min after injection of 3H-lysine. The increased incorporation of the label by both sympathetic ganglia was more marked in newborn than in 30-day-old animals. This result shows that protein synthetic activity in these ganglion cells is increased in SHR from the newborn stage. It is suggested that a congenital hyperfunction of sympathetic ganglia occurs in SHR. PMID- 2883755 TI - Ultrastructural study of the Sertoli cell and the limiting membrane in the seminiferous tubule of the adult cryptorchid rat. AB - Cryptorchidism was simulated in 13-15-day-old rats by severing the gubernaculum testis and fixing the testis to the abdominal wall. Ultrastructural examination of the testis was made 100 days after birth when a number of modifications to the seminiferous tubules were noted. Germ cells were scanty, with only occasional spermatogonia and primary spermatocytes persisting. The nuclei of Sertoli cells were regular and oval or indented in shape. Their cytoplasm was characterized by a rich smooth endoplasmic reticulum, lipid inclusions and mitochondria with tubulo-vesicular cristae indicative of steroidogenic activity. The decrease in the number of the germ cells induced a membrane rearrangement with numerous tight junctions and interdigitations between the Sertoli cells. Sertoli cell-specific junctional complexes were very extensive. The lamina propria of the seminiferous tubule appeared thickened and folded and the multilayered basal lamina had complex folds. After fixation with glutaraldehyde containing lanthanum, the latter substance was identified in the basal intercellular spaces of the seminiferous tubules indicating that the blood-testis barrier remains functional in the intra-abdominal testis. PMID- 2883756 TI - Myeloperoxidase deficient polymorphonuclear leucocytes: computerized planimetric estimations of cellular and nuclear size. AB - Quantitative estimations of the mean areas of cell, nucleus and cytoplasm in polymorphonuclear leucocytes (PMN) were performed by automated image analysis of blood smears from six patients with acute myeloid leukaemia. The PMN were qualitatively separated by a cytochemical staining method into two well-defined subpopulations i.e. myeloperoxidase (MPO)-normal and MPO-deficient PMN. MPO deficient PMN were characterized by a decreased size of the total cell (P less than 0.01), an increased size of the nucleus (P less than 0.01) and a decreased size of the cytoplasm (P less than 0.01). The resulting highly increased nucleus to-cytoplasm ratio in this specific PMN subpopulation bears a striking resemblance to cells in malignant tumours. The planimetric results in this study further support the concept that MPO-deficient PMN may be the progeny of leukaemic precursors. PMID- 2883757 TI - Effects of allopurinol pretreatment on myocardial ultrastructure and arrhythmias following coronary artery occlusion and reperfusion. AB - The effect of the xanthine oxidase inhibitor, allopurinol, on myocardial ultrastructure after left circumflex coronary artery occlusion (40 min) with or without reperfusion (60 min) was examined in rabbits. Pretreatment of rabbits for 7 days with allopurinol (0.1% in the drinking water) resulted in a lower incidence of ventricular fibrillation in both ischemic and reperfusion phases. However, the number of Q waves, ST-segment elevation and premature ventricular contractions were similar in both groups of animals. Examination of hearts from allopurinol-treated animals revealed a distinct decrease in ultrastructural alterations following ischemia and reperfusion. Among the subcellular organelles studied, allopurinol had a preferential protective effect on the mitochondria both during the ischemic and reperfusion phases. In the allopurinol-treated animals, most mitochondria were intact and the cristae network preserved. Our study suggests that the preservation of mitochondrial structural and functional integrity by allopurinol may be an important determinant of its protective actions in myocardial ischemic/reperfusion injury. PMID- 2883758 TI - Ultrastructural organization of nucleoli in benign naevi and malignant melanomas. AB - We have studied the ultrastructural organization of nucleoli in benign naevi and malignant melanomas. In benign naevus cells the nucleoli displayed a compact ribonucleoprotein distribution, with one or two large fibrillar centres. In malignant melanoma cells the nucleoli were large with an irregular, nucleolonema like ribonucleoprotein distribution and they exhibited numerous, small fibrillar centres. Statistical evaluation of the size of fibrillar centres indicated a mean value of 0.482 micron 2 +/- 0.136 SD for naevi and 0.221 micron 2 +/- 0.128 SD for malignant melanomas. These features, together with the more dispersed chromatin pattern of malignant melanoma nuclei compared with those of benign naevus cells, are proposed as diagnostic parameters which differentiate benign naevi from malignant melanomas at the ultrastructural level. PMID- 2883759 TI - Fatal mitochondrial cardiomyopathy in Kearns-Sayre syndrome with deficiency of cytochrome-c-oxidase in cardiac and skeletal muscle. An enzymehistochemical- ultra-immunocytochemical--fine structural study in longterm frozen autopsy tissue. AB - Morphological studies in a 26-year-old man with long-standing Kearns-Sayre syndrome, with cardiac arrhythmias and a fatal congestive cardiomyopathy, revealed a mitochondrial myopathy of both skeletal and myocardial muscle (Hubner et al. 1986). Histochemical investigation of cytochrome-c-oxidase showed multiple enzyme defects of both cardiac and skeletal muscle present in myocytes with normal and abnormal numbers of mitochondria demonstrated by ultracytochemistry. Immunohistochemical studies with antibodies against the holoenzyme and various subunits revealed that in the heart the enzyme defect affected both contractile and conductive fibres and was characterized by a severe reduction but not a complete loss of nuclear and mitochondrially coded immunoreactive enzyme protein. In skeletal muscle, however, where up to 30% of the fibres lacked enzyme activity, immunoreactivity was reduced only very occasionally. These results are most consistent with a defective enzyme assembly in the inner mitochondrial membrane and probably indicate heterogeneity of mitochondria, i.e. organ-specific pathological reaction patterns. PMID- 2883760 TI - Succinic dehydrogenase activity in germinal center macrophages in peripheral lymphoid organs of the rat. AB - Secondary lymphoid follicles in peripheral lymphoid organs (parathymic, mesenteric and inguinal lymph nodes and spleen) from young adult Wistar rats of both sexes were studied. Different numbers of tingible body macrophages containing aldehyde fuchsin-positive cytoplasmic granules of varying size, were present in the germinal centers. An identical staining pattern to that obtained with aldehyde fuchsin in terms of the number, distribution and size of positive cells was seen after staining for succinic dehydrogenase. PMID- 2883761 TI - Renal oncocytoma: origin from the collecting duct. AB - The histo- and cytogenesis of two cases of renal oncocytoma have been studied by cytomorphological and cytochemical methods. Transitions from collecting ducts into oncocytic tubules were observed at the light and electron microscopic levels. The fine structure of the oncocytes in tubules and tumors is described in detail. Cytochemically, the oncocytic tubules and oncocytomas share many characteristics with the distal nephron, especially the collecting ducts. A striking difference is the enhanced activity of succinic dehydrogenase which corresponds to the increase in the number of mitochondria in oncocytes. All the results suggest that renal oncocytoma originates from the collecting duct. PMID- 2883762 TI - Relationship between structure and T-lymphocyte maturation in human thymomas. Enzyme histochemical and immunohistological studies. AB - Twenty-six human thymomas were studied in an attempt to correlate their morphological appearance with the type and degree of T-lymphocyte maturation, as determined by acid alpha-naphthyl-acetate esterase (ANAE) activity and immunological analysis. Four normal human thymuses were used for purposes of comparison. Two morphological patterns were identified in the thymomas. The distinction was based largely on similarities between the neoplastic epithelial cells and normal cortical and medullary epithelial cells, and on the relative proportions of epithelial cells and lymphocytes. By these criteria "medullary" and "cortical" patterns were identified. In several thymomas both patterns were present in the same tumor ("mixed-type pattern"), producing alternating dark cortical-like areas and lighter foci of medullary differentiation. A good correlation was found between the two patterns and the phenotype of the T associated lymphoid component. ANAE activity, which was completely lacking in normal cortical thymocytes, was almost absent in the phenotypically immature T cells of cortical-type thymomas. By contrast, in the medullary-type thymomas, T cells showed immunological features in common with medullary thymocytes. This was characterized by strong ANAE activity in the majority of cells with a staining pattern corresponding to that of peripheral T-lymphocytes. In addition, most of the proliferating epithelial cells in medullary-type thymomas stained strongly with anti-cytokeratin and anti-epidermal-type keratin antisera. In the mixed-type thymomas the epithelial cell morphology and the immunohistochemical and enzymic features of the T-cells were found to be closely related to the respective cortical--or medullary-like areas. It was concluded that the various characteristics of normal thymic cortex and medulla studied are also present in thymomas. In particular, in medullar-type thymomas the presence of many of the features of normal thymic medulla, such as a squamous cell component, macrophages and interdigitating reticulum cells, may constitute a microenvironment which operates actively in T-cell education. This may account for the functional activities, characteristic of peripheral T-lymphocytes, which T-lymphocytes attain in these thymomas. PMID- 2883763 TI - Morphometrical evaluation of acute leukemic cells by electron microscopy. Discrepancy between morphological characteristics in FAB classification and electron microscopic morphometry. AB - Leukemic cells from 39 patients with acute leukemia (20 lymphocytic and 19 myelogenous) were examined by transmission electron microscopy and the nucleus and cytoplasm were measured on the micrographs with a computer-controlled image analyzer. The ratios between the areas of the nucleus and whole cell profile (nucleus/cell ratio), heterochromatin and euchromatin, the nucleolus and nucleus, and the degree of irregularity of the nucleus were compared between the two major types of leukemia studied. Acute lymphocytic leukemia (ALL) cells had a relatively larger nucleus and relatively less cytoplasm than acute myelogenous leukemia (AML) cells, and a greater proportion of the area of the nucleus was occupied by heterochromatin in ALL cells than in AML cells. According to the FAB classification, L1 cells are characterized by narrow, and L2 cells by wide cytoplasm based on light microscopic observation of smeared cells, and we confirmed these features by morphometry of May-Giemsa-stained blood smears. However, by electron microscopy there was no difference in the nucleus/cell ratio between L1 and L2 cells, this constituting a discrepancy between the results obtained by electron and light microscopic morphometry. In addition there was no difference in the degree of nuclear irregularity between L1 and L2 cells. Among AML subtypes, significant differences were observed only in the nucleus/cell ratio between M3 and M1, M2 or M4 cells, and in the heterochromatin/euchromatin ratio between M5 and M1, M2 or M3 cells. In conclusion, electron microscopic morphometry revealed marked differences between ALL and AML, but the differences among their subtypes defined by the FAB classification based on nonmorphometric light microscopy were less evident by electron microscopic morphometry. PMID- 2883764 TI - Abnormal T-lymphocytes in lymphomatoid papulosis. A cytomorphological study with a reconstruction of a major part of the cell differentiation cycle. AB - The abnormal cell population in lymphomatoid papulosis was studied by immunohistochemistry, light and electron microscopy in five cases. It resulted in a comprehensive description of all the main variants within the abnormal cell population. In one of the cases an irreversible intracytoplasmic process in the abnormal lymphocytes made it possible to demonstrate the derivation of lymphomatoid cells with cerebriform nuclei resembling the mycosis cells in mycosis fungoides from large histiocyte-like cells resembling the Reed-Sternberg cells in Hodgkin's disease. Variable numbers of the abnormal cells expressed Ki-1 reactivity in all four cases tested and T-cell associated antigens in two cases. PMID- 2883765 TI - Inhibited autophagic degradation during ACTH-stimulated growth of rat adrenal zona fasciculata. AB - Autophagic vacuoles (AVs) in adrenal parenchymal cells of the outer part of the zona fasciculata were investigated by means of electron microscopic morphometry in 40 adult male Sprague Dawley rats. Four test groups and four control groups received twice daily subcutaneous injections of ACTH (12.5 U/kg body weight) or physiological saline, respectively, for 3, 6, 9 and 12 days. At 12 days the total dry weight of the adrenals was increased in ACTH-treated animals from 17.2 to 71.0 mg (about fourfold) and the average volume of zona fasciculata cells from 1,500 to 5,100 microns3 (about threefold). The relatively larger increase in total mass reflects mitotic activity in the growing adrenal tissue. The calculated growth rate of total tissue expressed as the percentage increase in dry weight per day was 12% at day 3 and decreased to 4.6% at day 12 of ACTH stimulation. During the time interval investigated the cytoplasmic volume fraction of autophagic vacuoles was significantly reduced from 10 X 10(-5) in controls to 1 X 10(-5) in ACTH-treated animals (p less than 0.001). Assuming a half-life for AVs of 7.9 min (Papadopoulos and Pfeifer 1986), autophagic degradation of cytoplasm can be calculated as 1.3%/day in controls, but only 0.15%/day in ACTH-treated animals. Thus growth of 1.15%/day can be attributed to inhibition of autophagic degradation. Although this is only part of total growth, it is evident from the present results that anticatabolic growth induction is utilized nearly to its maximum in adrenocortical fasciculata cells under the influence of ACTH. PMID- 2883766 TI - Some acute effects of monochromatic ultraviolet B irradiation on mouse epidermis measured by the tetrazolium-reduction test and determination of DT-diaphorase activity, with reference to carcinogenesis. AB - Some acute epidermal effects of monochromatic ultraviolet B (UVB) irradiation on hairless mouse skin were measured by the tetrazolium test (TZT), and by determining the DT-diaphorase activity in epidermal cells. Dose response and time course studies were carried out after UVB irradiation at 280, 290, 297 and 302 nm. Appropriate UV doses at all the wavelengths increased the cellular deposition of formazan (TZT). At higher doses the epidermal cells became too injured to react. Wavelengths at 280 and 290 nm seemed more injurious than those at 297 and 302 nm. There was, however, no increase in DT-diaphorase activity after UVB irradiation. This indicates that the increased formazan deposition (TZT) after UVB is more likely to be caused mainly by membrane effects. Detoxification mechanisms which activate DT-diaphorase, as often seen after cellular contact with chemical carcinogens, are not involved. PMID- 2883768 TI - Re-examination of the effect of beta-adrenergic blocking agents on the proliferation of rat jejunal crypt cells using the stathmokinetic method. AB - Reports of the effects of beta-adrenergic receptor blocking agents on the proliferative activity of rat jejunal crypt cells are contradictory. According to Tutton and Helme (1974) a single injection of propranolol or practolol (10 mg/kg) increased the mitotic index twofold and shortened the duration of the cell cycle of the crypt cells. However, upon repeating the experiments with double the dose of propranolol, Maurer-Schultze et al. (1986) observed no such effects using cell kinetic methods with 3H-thymidine instead of the stathmokinetic method applied by Tutton and Helme. Since the discrepancy in the results may have been due to methodological differences the same stathmokinetic method used by Tutton and Helme has been applied in the present work. However, the results obtained with this method indicate no influence by propranolol on the proliferation of jejunal crypt cells even with a dose of 20 mg/kg. Consequently we were unable to confirm the stimulant effect of propranolol on crypt cell proliferation. The possible causes of the discrepancy between the present results and those of Tutton and Helme are discussed. PMID- 2883767 TI - Selective visualization of human dendritic reticulum cells in reactive lymphoid follicles by the immunohistochemical demonstration of the subunit A of factor XIII (F-XIIIa). AB - Immunohistochemical techniques have been used to localize clotting factor XIII subunit A in human reactive lymphoid follicles. The follicular dendritic reticulum cells (DRCs) were identified by the monoclonal antibodies R4/23 and OKB 7 as well as by their 5'-nucleotidase positivity. Follicular histiocytic reticulum cells (HRCs) were demonstrated by their acid phosphatase and non specific esterase reactions. Capillaries were selectively visualized by adenosine triphosphatase. The immunohistochemical demonstration of F-XIIIa was preferably carried out in combination with one or two of the above marker techniques, on the same cryostat section. The subunit A of factor XIII is present in follicular DRCs. Their selective immunohistochemical demonstration with antibody against F XIIIa requires formaldehyde fixation of cryostat sections. Similar fixation, however, is inappropriate for the demonstration of F-XIIIa reactivity of DRCs in paraffin sections. For this purpose, acetic acid-formalin fixation is useful. Follicular HRCs are consistently negative for F-XIIIa, contrary to the F-XIIIa positivity of sinusoidal and interfollicular HRCs. Developmental and functional implications of F-XIIIa reactivity in DRCs and HRCs are suggested. PMID- 2883769 TI - Viral oncogenes, proto-oncogenes and homoeotic genes related to cell proliferation and differentiation. AB - Molecular studies on viral oncogenes and their products have led to the discovery of physiological proto-oncogenes, involved in the control of cell proliferation and gene activation. Other genetic and molecular investigations, initiated in Drosophila melanogaster and continued in different multicellular eukaryotes, have made evident the homoeotic genes, which are directly correlated with cell specialization, in the complex processes of differentiation and morphogenesis. Both gene classes are conserved to a high extent during evolution. They are involved in the eukaryotic mechanisms of differentiation control and proto oncogenes, in particular, are related to malignant transformation. Some available data suggest a certain extent of relatedness between the gene products of both gene classes. A differentiation trigger model, including retroviral transposition, homoeotic genes and proto-oncogenes is discussed. PMID- 2883770 TI - [Determination of L-amino acid oxidase activity]. AB - Activity of L-amino acid oxidases was studied using several procedures. Optimal concentrations of L-lysine-alpha-oxidase, suitable for each procedure, were established involving highly purified preparations of the enzyme from Trichoderma sp. Estimation of the enzymatic activity carried out by means of calculation of the reduced cofactor accumulated led to two-fold exceeding of the results. The most sensitive procedure was based on evaluation of ammonium content in the reaction catalyzed by glutamate dehydrogenase and the procedure where peroxidase and o-dianizidine were used. PMID- 2883772 TI - [Immunoregulatory subpopulations of T-lymphocytes of systemic lupus erythematosus patients before and after hemosorption]. PMID- 2883771 TI - [Copper-containing amine oxidases of blood vessels (review of the literature)]. AB - Modern data on types, physico-chemical properties, physiological role of copper containing amine oxidase of blood vessels are reviewed. Properties of lysyl oxidase--specific copper-containing amine oxidase--are described. Importance of the enzyme for normal functions of connective tissue as well as alterations in the enzymatic activity under various pathological conditions are discussed. At the same time, properties and physiological functions of another copper containing amine oxidase of blood vessels, which uses polyamines as substrate, are considered. Effect of the copper levels on content of polyamines in body is discussed. PMID- 2883774 TI - [Regulation of Corynebacterium pekinense glutamine synthetase by the carbon and nitrogen source]. PMID- 2883773 TI - [Kindia virus--a new arbovirus isolated in the territory of the Republic of Guinea]. AB - Circulation of a new arbovirus named Kindia has been detected in Guinea Republic. The virus was isolated from ixodid ticks and blood-sucking mosquitoes and, on the basis of the studies done, has been classified into the antigenic group Paliam, genus Orbivirus, family Reoviridae. PMID- 2883775 TI - [Diagnostic problems in children with metachromatic leukodystrophy]. PMID- 2883776 TI - [Use of genetic technics in medical diagnosis exemplified by hemophilia A]. AB - Recent years have seen the rapid development of molecular probes for the detection of defective human genes. These react either directly with the gene in question or with a DNA sequence which lies in close proximity to the gene and which exhibits polymorphism. In the case of haemophilia A two probes were found that belong to the latter category. We have used one of these probes to test its usefulness in the detection of carriers of haemophilia A. For these tests DNA was isolated from blood cells, but can, in principle, be obtained just as easily from other cells or tissues. The results of tests on several families show that the gene technological method is much more precise and sensitive than conventional methods used so far to detect carriers. In all cases a clear assertion was possible as to whether or not the person in question was a carrier of haemophilia A. The method should be applicable to prenatal diagnosis. PMID- 2883778 TI - [Eicosanoids in chronic inflammatory intestinal diseases]. AB - Eikosanoids (prostaglandins, thromboxanes, prostacyclins, hydroxyfatty acids, leucotriens) are metabolites of arachidonic acid and are of importance for many functions of the gastro-intestinal tract. They increase the enteral secretion of water, sodium and chloride ions, stimulate inflammatory and immune reactions, inhibit the proliferation of the colon epithelium and regulate by means of cytoprotection the peristalsis and the intestinal blood supply. Though in chronic inflammatory intestinal diseases the concentrations of metabolites of arachidonic acid are increased up to now there are no conclusive proofs for their causal pathogenetic role. PMID- 2883777 TI - [Do vasodilators help in chronic heart failure?]. AB - The value of vasodilator drugs in the treatment of patients with chronic congestive heart failure is reviewed on the basis of the randomized double-blind, placebo-controlled trials so far published. Apparently, venous, or combined venous and arteriolar dilation in addition to cardiac glycosides and diuretics may produce long-term improvement in advanced stages of heart failure. Vasodilators with isolated afterload reducing properties seem to be of limited value. Long-term improvement with nitrates and alpha-receptor blocking agents is often modest, probably due to development of tolerance. The most striking results were observed with converting enzyme inhibitors: they evoke virtually no tolerance, improve haemodynamics at rest and during exercise, relieve symptoms of heart failure and are even suggested to reduce mortality. PMID- 2883779 TI - [Progress in the treatment of gastroenterologic diseases in advanced age]. AB - Therapeutic advances in gastroenterology benefit patients of all ages, although the elderly ones receive more benefits than others. The latter is especially true for operative endoscopy where, in some cases, otherwise high-risk patients can be spared an operation. Peptic stenosis, which is common in elderly patients as a result of reflux oesophagitis, can be treated by bougienage. Bleeding from gastric and duodenal ulcers can cause problems in the elderly. In most cases endoscopic treatment by electro- or laser coagulation, or by sclerotherapy can avoid the need for surgery, or at least the conversion of an emergency operation into an elective one with a better prognosis is possible. Adenomata in the colon are common causes of chronic blood loss and can become malignant. They should be removed endoscopically. Another typical age-dependent finding, which can be treated by electro- or laser coagulation in the colon are angiodysplasia, which can be the origin of massive haemorrhage. It is now becoming accepted that in an elderly patient, stones in the common bile duct should be managed by endoscopic sphincterotomy and gallstone removal. This approach is safer and quicker than conventional surgery. The practice of endoscopic drainage by insertion of a prosthesis in cases of malignant obstructive jaundice is although increasing in older patients. PMID- 2883780 TI - [The rationale of pain therapy in the aged]. AB - Today elderly persons represent the largest group of pain patients. Geriatric patients show different pharmacokinetic and pharmacodynamic features of local and systemic analgetic drugs, but there is no evidence that pain threshold changes with the age. The advanced knowledge of the physiological processing of pain (i.e. the role of prostaglandins) influences the treatment and the use of certain drugs. A successful therapy for elderly patients needs a planned action, starting with an exact analysis of the patient's social background, organic functions and pain status. During the course of therapy the patient needs a continuous guidance and his family should have thorough informations to reach an optimal effect. If there is no indication for electrotherapy or regional blocks, we start with a peripherally acting nonnarcotic analgesic. The next step is a combination between this drug and a psychopharmacon. If necessary we add narcotics of the partial agonist type. In case this is not effective we combine a psychopharmacologic agent with a potent agonist narcotic (like morphine). The next step includes the different kinds of spinal opiate application. With these methods we are able to carry out pain therapy (even in difficult cases) providing a high level of well being, combined with a high grade of physical mobility and mental alertness. PMID- 2883781 TI - [Tiapride in the treatment of irreversible tardive dyskinesia--initial experiences]. AB - Twelve patients on a chronic psychiatric ward with NL-induced permanent TD were treated with 300 mg tiapride daily for at least 3 weeks. Clinical assessment of TD was performed with AIM-Scale before and after 3 weeks' therapy, showing a significant effect of treatment. These preliminary findings were controlled in a blind study, showing again a significant therapeutic effect of tiapride. PMID- 2883782 TI - Coated vesicles in the muscle-blood zone of an insect asynchronous flight muscle. PMID- 2883783 TI - [Pathogenesis of Dupuytren's disease]. AB - Liver studies performed in 47 patients with Dupuytren's contracture revealed a high level of hepatitis A contamination; in addition, procollagen III levels were distinctly lowered as compared to normal values, and liver enzyme values were pathologic in 32%. A disturbance of collagen metabolism must, therefore, be considered as a possible cause of Dupuytren's contracture. PMID- 2883784 TI - Age and dose interval as factors in agglutinin formation to pertussis vaccine. AB - The agglutinin response to pertussis agglutinogens in diphtheria-tetanus pertussis (DTP) vaccine was determined in human infants inoculated initially at ages four weeks to eight months. The effects of age at the time of initial dose and the interval between subsequent doses were specifically evaluated. Our findings demonstrate that optimum agglutinin production is best achieved with DTP vaccine by beginning immunization at five months of age or later followed by a second dose at eight weeks or more. Variation in the two variables, age and dose interval, decreases the likelihood of an optimum agglutinin response. PMID- 2883785 TI - [Pathogenesis of frostbite]. PMID- 2883786 TI - Immunological regulation of hematopoietic stem cell differentiation by interleukin-3. PMID- 2883787 TI - Information explosions in an old-new research domain. First International Workshop on Neuroimmunomodulation. PMID- 2883789 TI - Q and TL region genes and protein products. A status report. PMID- 2883788 TI - Structure and function of human complement receptors: 1985. PMID- 2883791 TI - [Integrative nature of Yersinia pestis virulence]. PMID- 2883790 TI - Molecular basis for the bidirectional modulation of the neuroendocrine and the immune systems. AB - Experimental evidence in many fields point towards the existence of a bidirectional communication between the neuroendocrine and immune systems. The immune response unifies the endocrine, nervous and immune systems. This integrated microenvironment includes lymphoid cell, nonlymphoid cells, cholinergic and adrenergic neurons and their neurohumoral products, biologically active substances including the cytokines and lymphokines produced by lymphoid and nonlymphoid cells, hormones and neuropeptides released by endocrine glands and regulatory cells of the brain, membrane and intracellular receptors which make possible the immune connections, and ions which are involved in the transmission of information and the higher nervous system activity which influences the immune microenvironment. Neuroendocrine circuits constitute only one type of efferent link between the brain and the immune compartment. The autonomic nervous system, via its innervation of many peripheral target tissues throughout the body, might also prove to be an important link to the immune system. While the precise mechanism(s) of neuroendocrine-immune relationships may not as yet completely defined, it is apparent that such interrelationships exist. PMID- 2883792 TI - [Pathogenesis of cerebral disorders in hepatocerebral dystrophy]. AB - On the basis of data obtained in the course of long-term observation of more than 60 patients with hepatocerebral dystrophy and analysis of the literature the authors consider the problems related to the pathogenesis of cerebral disorders in this disease. It has been found that the underlying mechanisms of the disorder is chronic intoxication of the central nervous system which is induced by the glut of "non-ceruloplasmin" copper and brings about a cascade of secondary metabolic disturbances, including defect of the amino acid pool in the blood plasma, zinc deficit, and disorders of redox processes. The possible role of each of these disorders has been considered in the pathogenesis of cerebral disturbances associated with hepatocerebral dystrophy. PMID- 2883793 TI - [Complex use of benzodiazepines, lithium salts and haloperidol in the treatment of obsessive movements and tics of different origin]. AB - Seventy-two children and adolescents with obsessive movements and tics of residual-organic etiology were treated by combined application of benzodiazepins (diazepam, phenazepam), lithium carbonate and haloperidol. The nature of obsessive syndromes and tics is considered in the light of the theory of generator mechanisms of neuropathological syndromes. The use of the studied combination due to its synergic action on the structures of the pathological system elicited a good therapeutic response while using lower doses of each drug (half to two-thirds of the conventional age-specific dosage). Reduction in drug doses in combined therapy decreases the risk of side effects and complications. The above treatment was followed by disappearance of essential and facultative symptoms in 21 patients, considerable improvement with a marked reduction of facultative symptoms in 22 cases, clear-cut improvement in combination with decreased facultative symptomatology in 14 patients, and insignificant improvement in 6 patients. PMID- 2883794 TI - Positive effects of ketamine v. metomidate anesthesia on cardiovascular function, oxygen delivery and survival. Studies with a porcine endotoxin model. AB - Pulmonary and cardiovascular function, oxygen delivery and mortality were compared in endotoxemic pigs spontaneously breathing air and with continuous i.v. infusion of ketamine anesthesia (n = 10) or the equianesthetic dose of metomidate (n = 10). Continuous 6-hour i.v. infusion of endotoxin caused profound pulmonary and cardiovascular derangement in both groups. Cardiac output, mean arterial blood pressure, oxygen delivery and base excess were significantly higher and pulmonary vascular resistance significantly lower from 2-3 hours onwards in the ketamine than in the metomidate group. Six-hour survival was 6/10 and 1/10 in the respective groups. Death was presumably due to insufficient oxygen delivery in relation to tissue demand, reflected in the metomidate group's low base excess values. Control, non-stressed pigs showed no notable physiologic changes with either anesthetic regimen. The study demonstrated the importance of the type of anesthesia in stressful endotoxemic animal models. Although extrapolation of animal data requires great caution, the results may favor use of ketamine over etomidate (the clinical analogue of metomidate) in septic shock states requiring surgical intervention. PMID- 2883795 TI - Drugs recently released in Belgium: misoprostol, almitrine bismesylate. PMID- 2883796 TI - Somatostatin inhibits insulin-stimulated amino acid uptake into cultured rat myoblasts. AB - The effects of somatostatin on the acute metabolic actions of insulin on newborn rat myoblasts in culture has been examined during monolayer culture. Somatostatin significantly inhibited the insulin-stimulated uptake of [3H]leucine and [3H]amino-isobutyric acid into myoblasts but had no effect on basal (unstimulated) uptake of these two substances. The lowest concentration of somatostatin to have a significant effect was 10 micrograms/l, and this was apparent in all the experiments undertaken. The inhibitory effect of somatostatin was seen at all effective concentrations of insulin used (0.3-1 U/l). These findings lend support to the concept of an endocrine role for somatostatin in vivo and suggest that a peripheral antagonism may exist between circulating insulin and somatostatin on anabolic processes such as nutrient uptake into cells. PMID- 2883797 TI - The effect of minisomatostatin on anomalous growth hormone responses in acromegaly. AB - Twelve patients with active acromegaly were treated with the long-acting somatostatin analogue SMS 201-995 at a dose of 50 micrograms sc twice daily in the first 2 weeks of treatment and 100 micrograms twice daily thereafter. Four hours after the first injection of SMS, GH levels became normal in 8 of the 12 patients. The GH response after hpGRF administration was strongly suppressed by SMS. Paradoxical GH responses to TRH disappeared in 6 out of 7 patients during SMS. Paradoxical GH responses to LHR, however, persisted in 4 out of 4 patients. Paradoxical responses of GH after glucose loading disappeared in 2 out of 2 patients. We conclude that SMS normalizes most anomalous growth hormone kinetics in acromegaly. This drug offers a new tool in the treatment of this disease. PMID- 2883798 TI - Characterization of growth hormone-releasing hormone stimulation of the endocrine pancreas: studies with alpha- and beta-adrenergic and cholinergic antagonists. AB - The 40 aminoacids residue of pancreatic growth hormone-releasing hormone stimulates the secretion of insulin, glucagon, an somatostatin from the pancreas. To determine whether this stimulation of islet hormone secretion is mediated via adrenergic or cholinergic receptor sites, we studied the effects of 30 nmol/l of the growth hormone-releasing hormone on the release of insulin, glucagon, and somatostatin in the presence of either alpha-adrenergic (phentolamine), beta adrenergic (propranolol) or cholinergic (atropine) blocking agents. The responses to the growth hormone-releasing hormone were not significantly modified by adrenergic or cholinergic blockers. The findings rule out an interaction with adrenergic and cholinergic receptors on islet cells. It is at present unknown whether the growth hormone-releasing hormone stimulates islet hormone secretion via an interaction with specific growth hormone-releasing hormone receptors or vasoactive intestinal peptide receptors. PMID- 2883799 TI - Fertility in unilateral cryptorchidism: review of 104 cases. AB - Testicular maldescent adversely affects spermatogenesis, therefore the primary purpose of its correction is to preserve subsequent fertility. However, many patients, even with unilateral cryptorchidism, are infertile in spite of successful prepubertal orchidopexy. Out of our 104 patients treated for unilateral cryptorchidism before puberty, a decreased sperm density (spermatic concentration less than 20 X 10(6)/ml) was observed in 64 cases (61.54%), a normal sperm count in 32 cases (30.77%) and azoospermia in the remaining 8 cases (7.69%). Both congenital and acquired abnormalities may be associated with development of bilateral testicular impairment in unilateral cryptorchid males. PMID- 2883801 TI - The interaction of pancuronium and vecuronium with cardiac muscarinic receptors. AB - The interaction of vecuronium, a monoquaternary analogue of pancuronium, with the cardiac muscarinic receptors in canine hearts was investigated in vitro by [3H] QNB binding assay and compared with that of pancuronium. Both pancuronium and vecuronium, which are nicotinic antagonists of competitive types, inhibited the binding of [3H] QNB to cardiac muscarinic receptors with values of IC50 of 5.41 X 10(-7) mol/l and 3.97 X 10(-6) mol/l respectively. According to the Kd and Bmax values on the Scatchard plot, pancuronium, while not influencing the number of receptors, had a 3-fold greater inhibitory effect than vecuronium on the affinity of the muscarinic receptors. The KI values of vecuronium and pancuronium showed that pancuronium had a 7.3-fold greater affinity with the receptors than vecuronium. We concluded that vecuronium had a direct inhibitory action on the binding of [3H] QNB to the canine heart muscarinic receptors, but this action was much weaker than pancuronium. PMID- 2883800 TI - Anti-HTLV-III and anti-HTLV-I antibodies and T cell subsets in hemophiliacs living in HTLV-I endemic and nonendemic areas of Japan. AB - Sera from 154 hemophiliacs, including 132 with hemophilia A and 22 with hemophilia B, were examined for antibodies against human T cell lymphotropic virus type III (HTLV-III) and type I by strip radioimmunoassay based on the Western blotting technique. Sixty-two patients lived in Kyushu, a known endemic area of HTLV-I and 92 patients lived in Tokyo, a nonendemic area of HTLV-I. Results showed a prevalence of HTLV-III antibodies of 64.5% in Kyushu and of 57.6% in Tokyo. There were no significant differences between these two groups. Helper/suppressor (T4/T8) ratios of seropositive patients were 0.69 +/- 0.41 and those of seronegative patients were 1.05 +/- 0.56. Ratios of both groups were lower than those of normal healthy people (1.35 +/- 0.45). Our findings confirmed that hemophiliacs living in an HTLV-I endemic area and those living in a nonendemic area in Japan equally possessed antibodies to HTLV-III. Low T4/T8 ratios and increases of serum IgG and IgM levels were found even in seronegative hemophiliacs. PMID- 2883803 TI - [Anatomical studies of a case of retentio testis in a cadaver of advanced age]. PMID- 2883802 TI - Somatostatin cells in the gastric mucosa of small ruminants. Immunohistochemical study. AB - The distribution of somatostatin cells was investigated immunohistochemically in the epithelium of the abomasal mucous membrane of sheep and goats. Tissue samples were taken from different areas at the lesser and greater curvature of the glandular stomach. More somatostatin cells per 0.5 mm2 were found in sheep than in goats, predominantly in the pyloric gland region. In the pyloric area of both species the mucosa in the greater curvature contained more immunoreactive cells than the one in the lesser curvature. A few somatostatin cells with basal cytoplasmic processes of the 'open type' were observed over the entire abomasal mucosa. PMID- 2883804 TI - Voluntary movement dysfunction in Huntington's disease and tardive dyskinesia. AB - Psychiatric patients with tardive dyskinesia (TD) may be difficult to distinguish from those with Huntington's Disease (HD), who frequently have psychiatric symptoms. This study compared 14 patients with HD with 21 patients (15 schizophrenics and 6 with affective disorder), matched for involuntary movements, using a quantitated neurological examination and other objective and semi objective tests. The HD group was significantly more impaired on measures of voluntary movement and saccadic eye movements. When the psychiatric group was subdivided, voluntary motor impairment was most marked in schizophrenics with both TD and parkinsonism. The implications of these findings are discussed. PMID- 2883805 TI - Somatostatin in multiple sclerosis. AB - The detection of somatostatin, a 14 aminoacid peptide, in human brain and cerebrospinal fluid (CSF) initiated examinations by radioimmunoassay and immunocytochemical technique to elucidate its origin, localization, function, and possible significance in central nervous system disorders. The present survey deals with these aspects with special reference to multiple sclerosis (MS) and to correlation between disease activity and somatostatin content and variations in CSF. PMID- 2883806 TI - Conjunctival nerve pathology in multiple endocrine neoplasia. A case report. AB - A 31-year-old male with typical clinical features of multiple endocrine neoplasia type 2b (MEN 2b) was subjected to conjunctival biopsy. The patient had previously been operated for pheochromocytoma and medullary carcinoma of the thyroid. He came for ophthalmologic consultation because of redness and irritation of the eye due to dry eye syndrome. The conjunctival biopsy taken from his left eye revealed not only an increase in the number of conjunctival nerves but also an increase of their axons. The ultrastructure of the nerves was mostly normal, but the perineurium was often incomplete, and the interaxonal space appeared to be enlarged. Immunohistochemically, SP-, neurofilament- and, unexpectedly, leucine enkephalin-positive nerve fibres were demonstrated in the conjunctival stroma. The rat is the only species in which enkephalin-like immunoreactivity has been described in the anterior segment of the eye. Thus, the presence of enkephalin positive nerves in the conjunctiva of our MEN 2b patient may reflect a profound neural alteration. PMID- 2883807 TI - Insulin secretion induced by allogeneic lymphocytes in genetically diabetic mice C57BL/KsJ mdb. AB - Insulin and somatostatin (SRIF) secretion induced by alloantigen were studied in genetically diabetic mice from the C57BL/KsJ mdb-mdb strain. Diabetic (db) mice injected with allogeneic lymphocytes (A.L.) did not show any increase in their second phase of 27.5 mM glucose stimulated secretion and slightly increased their first phase. Normal A.L. injected mice showed a significant increase in both phases of 27.5 mM glucose stimulated secretion. SRIF secretion of A.L. injected normal and diabetic mice did not significantly differ from that obtained when injected with syngeneic lymphocytes. Lymphocytes from db mice injected into allogeneic mice caused an insulin secretion similar to that produced by allogeneic lymphocytes from non-diabetic mice. Lymphocytes from db mice injected into normal syngeneic mice caused an insulin secretion which was not significantly different from the one caused by syngeneic lymphocytes from non diabetic mice, and is smaller than the secretion caused by A.L. injection. In summary, db mice showed an impaired hormone response to alloantigenic stimulus, while their lymphocytes maintained their alloantigenic action. PMID- 2883809 TI - Autoregulation of capillary pressure and filtration in cat skeletal muscle in states of normal and reduced vascular tone. AB - The controversial hypothesis that capillary pressure (Pc) is autoregulated in response to arterial pressure (PA) alterations was tested in sympathectomized cat skeletal muscle by studying the relation between Pc and PA under conditions of well preserved vascular tone and reactivity, during papaverine-induced maximal vasodilatation (passive vascular bed), and during impaired vascular reactivity caused by preparatory surgery, or by low dose isoproterenol administration. The latter states resembled such under which Pc autoregulation unintentionally seems to have been studied previously. Capillary pressure was assessed with the Pcvenule method for continuous direct pressure recordings from capillaries/postcapillary venules (Mellander et al. 1987) and simultaneously derived from observed net transvascular fluid flux divided by CFC. Resistances in the whole vascular bed and in its pre- and postcapillary segments (Ra and Rv) were determined from recordings of blood flow, PA, Pc, and PV. During preserved vascular reactivity, Pc was found to be virtually constant, that is, almost perfectly autoregulated, over the PA range from 50 to 180 mmHg, whereas in the passive vascular bed there was a direct linear relation between Pc and PA (y = 0.137x + 11.69; r = 0.97). The delta Pc/delta PA ratio was about 1/70 in the normal reactive, and 1/7 in the passive, vascular bed, implying an increase in Pc by 1 mmHg for every 70 mmHg and every 7 mmHg increase in PA, respectively. Capillary pressure autoregulation was explained by precise adjustments of Ra/Rv in relation to PA elicited by myogenic and metabolic regulatory mechanisms. This protective reaction against plasma loss during increased PA was abolished during maximal vasodilation, and was much impaired by surgical trauma, partly via a beta adrenergic inhibitory effect, and by isoproterenol, in turn causing gross transcapillary fluid fluxes. The latter findings might explain failing Pc autoregulation in some previous studies undertaken under seemingly similar conditions. PMID- 2883808 TI - Immediate reduction of blood pressure and sympathetic nerve activity after beta blockade in anaesthetized cats with deafferentiated arterial baroreceptors. PMID- 2883810 TI - Autoradiographic location of beta-adrenoceptor subtypes in cat colon smooth muscle. AB - In order to localize beta-adrenoceptors 125I-(-)pindolol (IPIN) was used in binding to sections from cat colon. The binding characteristics for IPIN to beta adrenoceptors on colon sections were estimated by demonstrating reversible binding in the presence of isoprenaline and by steroselective binding to the isomers of propranolol. The binding of IPIN to both beta 1- and beta 2 adrenoceptors was shown by biphasic displacement curves in the presence of the selective beta-adrenoceptor compounds betaxolol, ICI 118.551 and procaterol. The colon sections were found to contain proportions of beta 1-adrenoceptors (30-50%) and beta 2-adrenoceptors (50-70%). In the autoradiographic studies, 100% of the developed grains after exposure of IPIN to the photographic emulsion were displaced by 50 microM of isoprenaline. By microscopic counting at autoradiographic grains, 30-40% of the grains were found in the circular smooth muscle, while 60-70% of the grains were found in the longitudinal smooth muscle. A concentration of 2 nM ICI 118.551 completely displaced all grains in the circular smooth muscle and partly displaced those found in the longitudinal smooth muscle. A high concentration of ICI 118.551 (1 microM) displaced all grains above background from the smooth muscle. It is concluded that the circular smooth muscle only contains beta 2-adrenoceptors, while longitudinal smooth muscle may contain a proportion of beta 1-adrenoceptors. Whether such a location of beta adrenoceptors can be related to the beta 1-adrenoceptor-mediated inhibition of colon motility can not be clarified from these studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883812 TI - Blockade of central beta-adrenoceptors attenuates tremor induced by 5 hydroxytryptamine (5-HT)-receptor activation in rats. AB - The effect of beta-adrenoceptor antagonists, varying in lipophilicity and receptor selectivity, were studied on tremor elicited by L-5-hydroxytryptophan (L 5-HTP) in rats pretreated with a peripherally acting decarboxylase inhibitor and a monoamine oxidase inhibitor, or by the directly acting 5-HT agonist 5-methoxy N,N-dimethyltryptamine (5-MeODMT). Plasma levels of the beta-adrenoceptor antagonists were determined simultaneously. The non-selective lipophilic adrenoceptor antagonist propranolol was found to dose-dependently reduce tremor intensity, whereas the non-selective hydrophilic adrenoceptor antagonist sotalol had no effect, indicating a central site of action. Furthermore, beta 1-selective blockade with the adrenoceptor antagonist metoprolol had no effect on tremor intensity, whereas the beta 2-selective antagonist ICI 118,551 dose-dependently suppressed tremor intensity, suggesting that the beta-adrenoceptor subtype involved is of the beta 2-type. These results suggest that blockade of centrally located beta 2-adrenoceptors are able to attenuate the tremor response following 5-hydroxytryptamine receptor activation. PMID- 2883811 TI - Modulation of oxotremorine-induced tremor by central beta-adrenoceptors. AB - The muscarinic agonist oxotremorine was used to induce tremor in rats pretreated with methylatropine. An objective assessment of tremor intensity was accomplished by means of an accelerometer-based recording system. The non-selective, lipophilic beta-adrenoceptor antagonist propranolol dose-dependently suppressed tremor intensity, whereas the R-isomer of propranolol was without effect, verifying beta-adrenoceptor involvement. Since the hydrophilic, non-selective beta-antagonist nadolol was ineffective, the effect appears to be located inside the blood-brain barrier. The beta 2-selective antagonist ICI 118, 551 dose dependently reduced tremor intensity, whereas selective blockade of beta 1 adrenoceptors with metoprolol had no effect, indicating the participation of a beta 2-adrenoceptor. On the other hand, the lipophilic beta 2-agonist clenbuterol dose-dependently enhanced tremor induced by oxotremorine. Determination of circulating plasma catecholamine concentrations revealed that the effect of beta antagonists on tremor was not secondary to an effect on the oxotremorine-induced rise in catecholamine levels. Thus, the results suggest that beta 2-adrenoceptors located inside the blood-brain barrier are able to modulate oxotremorine-induced tremor in rats. PMID- 2883813 TI - [In vitro and in vivo comparative studies of various barbituric acid derivatives]. PMID- 2883814 TI - Cortical atrophy and white matter density in the brains of schizophrenics and clinical response to neuroleptics. AB - The relationship between clinical response to neuroleptics and brain morphology as revealed by CT scans was evaluated in a sample of 39 patients with schizophrenia and schizoaffective psychosis. Four measures of brain morphology previously shown to differ between schizophrenics and patients with headaches - white matter density, asymmetry in brain white matter density, sulcal width and global cortical atrophy - did not correlate with clinical improvement after 3 weeks treatment with constant doses of neuroleptics. These brain morphology measures also did not correlate with baseline psychopathology scores. The same results were found with scales or subscales reflecting primarily positive symptoms of schizophrenia as well as those reflecting primarily social withdrawal. PMID- 2883815 TI - Morbidity and mortality in tardive dyskinesia: associations in chronic schizophrenia. AB - A population of 101 chronic schizophrenic inpatients were assessed for the presence or absence of tardive dyskinesia, and followed up 32 months later. At follow up, the mortality rates in 44 patients with and 57 patients without involuntary movements were 16% vs. 9% respectively; this difference widened when only the more prominent involuntary movements were considered. Of those surviving, patients with tardive dyskinesia were much more likely to contract an attack of respiratory tract infection, and to do so on multiple occasions, and tended to suffer from more cardiovascular disorders. They appeared more likely to show smoking-related pathology. Chronic schizophrenic patients with tardive dyskinesia constitute a more biologically disadvantaged group, suggesting a broader disease concept of the syndrome. PMID- 2883817 TI - Saccadic eye movements as a measure of residual effects: temazepam compared with other hypnotics. AB - Eye movements are classified into two categories: quickly running saccades and smooth pursuit movements. Saccades are fast conjugate eye movements with a preprogrammed direction, amplitude, and speed course; their purpose is to register new objects in the visual field. The duration and velocity of saccadic eye movements are very much dependent on vigilance. Comparisons were made with a number of psychometric tests [d 2 Durchstreichtest (cross out test), Viennese determination apparatus, and flicker fusion frequency] and the velocity of fast eye movements. The results of three separate investigations are presented. Standardization was undertaken in 100 healthy volunteers, 50 male and 50 female subjects aged between 20 and more than 50 years were included. In an open parallel group study, comparisons were made between various hypnotics with different half-lives (temazepam, flunitrazepam, flurazepam, and phenobarbital). There were 10 healthy volunteers in each group, and medication was taken as a single night-time dose for 7 nights. In a double-blind study, temazepam (20 mg/day) was tested against flunitrazepam (2 mg/day). Dosing lasted 7 days. A marked impairment of the saccadic eye movements was observed with flunitrazepam but not with temazepam. Of all the benzodiazepines tested, only temazepam had no influence on the parameters of the saccade test. These results can be explained by temazepam's short half-life and also by the fact that no active metabolites are formed. PMID- 2883816 TI - Zuclopenthixol acetate in Viscoleo--a new drug formulation. An open Nordic multicentre study of zuclopenthixol acetate in Viscoleo in patients with acute psychoses including mania and exacerbation of chronic psychoses. AB - Eighty-three acutely disturbed, psychotic patients were included in an open multicentre study. The aim of the study was to evaluate the clinical effect of zuclopenthixol acetate in Viscoleo (CPT-A). Each patient received from one to four intramuscular injections of CPT-A during the 6-day study period. The duration of action after one injection was between 2 and 3 days and doses from 50 mg to 150 mg were sufficient for most patients. Treatment with CPT-A caused a pronounced and rapid reduction of the psychotic symptoms. At the end of the 6-day test period the mean total score on BPRS in acute non-manic and exacerbated chronic patients was reduced by more than 50 per cent. In acute manic patients the mean total score on BRMS was reduced by 57 per cent already 1 day after injection. Rapidly after the injection of CPT-A a useful short-acting sedation can be expected, but the risk for oversedation even after a second injection is low. The frequency of unwanted effects, including extrapyramidal reactions, was low and the severity of symptoms was most often mild. With a rapid onset of action, a duration of effect of 2 to 3 days, and few and mild side effects, CPT-A offers advantages over the neuroleptic preparations conventionally used in the initial treatment of acutely disturbed, psychotic patients. PMID- 2883818 TI - Aspects of driving after hypnotic therapy with particular reference to temazepam. AB - In a double-blind study, 32 outpatients with sleep disorders received oral doses of temazepam 20 mg (n = 16) or flunitrazepam 2 mg (n = 16) once a night for 7 days. On the morning after the first and seventh doses, patients completed psychomotor tests and a real driving test on the road over a 25 km course. The road test included a 1 km straight stretch driven at constant speed. In the car, various parameters were automatically recorded every second for approximately 60 minutes. These included angular velocity of steering, lateral acceleration and velocity. An optimization quotient, a measure of the efficiency of information processing in the driver-vehicle-road interaction, was derived from these parameters. An observer recorded driving performance by scoring standardized tasks. After a single dose of temazepam, the improvement in driver performance as shown by a decreased optimization quotient was significantly different to the deterioration seen after flunitrazepam (p less than 0.05). After the seventh dose, this trend was still apparent but was not statistically significant. After both one and seven doses, the angular velocity of steering was significantly decreased in the temazepam group compared with an increase after flunitrazepam (p less than 0.001). Over the straight, this deterioration in steering ability in the flunitrazepam group was apparent after one dose and reached statistical significance compared with temazepam after seven doses (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883820 TI - The clinical use of hypnotics: indications for use and the need for a variety of hypnotics. AB - Insomnia may be categorized as difficulty falling asleep, frequent awakening, early awakenings or a combination of each. The ideal hypnotic must promote rapid sleep onset and maintain sleep throughout the night while allowing the patient to awake refreshed the following day. Several benzodiazepines, with differing pharmacokinetic and pharmacodynamic profiles are presently available. All are clinically effective and not only elimination half-life but also dosage prescribed and pattern of distribution are important factors for determining treatment response. Hypnotics have been divided into those with long elimination half-lives (e.g. nitrazepam, flunitrazepam, flurazepam), those with intermediately long half-lives (brotizolam, loprazolam, lormetazepam, temazepam) and those with short half-lives (midazolam and triazolam). Carry-over effects into the morning such as excessive daytime sleepiness or drowsiness are related to drug half-life, dosage and pattern of distribution. In equipotent dosages most controlled clinical trials have found no significant differences between the various benzodiazepine hypnotics. Nevertheless, clinicians in general tend to use long half-life benzodiazepines in patients who have difficulties maintaining sleep and short half-life benzodiazepines for treating sleep onset insomnia. Intermediately long half-life, benzodiazepines are used for both indications and most clinicians feel that the choice of hypnotic should not only be influenced by elimination half-life or the dosage used, but by individual patient preference. Hypnotics should be used for only short periods of time and in those patients for whom a more chronic use is indicated, they should be used only on an intermittent basis. PMID- 2883819 TI - The effects of repeated doses of temazepam and nitrazepam on several measures of human performance. AB - The effects of six nightly doses of temazepam (20 mg), nitrazepam (10 mg) and placebo on saccadic eye movements, critical flicker fusion threshold, choice reaction time and mood were studied in eight volunteers. Performance was measured on nights 1 and 6 of each treatment. Nitrazepam produced a residual performance impairment on night 1 that disappeared by night 6, despite higher serum concentrations of the drug on the sixth night of treatment. Temazepam, with a shorter elimination half-life, produced no significant performance impairment on night 1, but by night 6 a significant impairment of saccadic eye movements (p less than 0.05) was seen 1 hour after drug intake. We conclude that tolerance to the sedative action of nitrazepam developed over the 6-night period of the study. No evidence of tolerance was seen with temazepam. No residual effects of temazepam (20 mg) were seen the morning after the night-time drug administration. PMID- 2883822 TI - Benzodiazepine hypnotics in the elderly. AB - A review is presented of the changes that occur in the pharmacodynamics of benzodiazepines during normal ageing and as a result of disease. Controlled studies in which subjects of different ages have received single doses of diazepam, temazepam, nitrazepam and flunitrazepam have consistently shown an increase in the response to benzodiazepines in the elderly which is not explained by the effects of disease or by altered plasma concentrations. In general, healthy elderly subjects have a 2-3 fold greater response compared with the young. This change appears to be due to a change in the post-receptor mechanism of action. Cerebral diazepam concentrations are similar in young and elderly rats, though older animals also show an increased response and no consistent changes have been demonstrated in brain receptor binding. However, benzodiazepine induced increases in GABA binding and GABA-induced increases in post-synaptic inhibition have been reported to be greater in aged animals. Regular daily dosing with most benzodiazepines leads to drug accumulation which is proportional to the elimination half-life. Regular dosing with diazepam, chlordiazepoxide, nitrazepam and flurazepam has also been found to produce more sedation in the elderly, particularly long stay patients who have a high incidence of dementia, and those with a low albumen or chronic renal failure. A controlled trial of 1 week's dosing with 5 mg of nitrazepam or 20 mg of temazepam in elderly in-patients showed that these doses produced significant impairment of psychomotor performance the morning after the last dose. Only about 50% of the patients were affected and many of these were frail patients with mild dementia on rehabilitation or long stay wards. The doses prescribed for these types of patients should not exceed 2.5 mg of nitrazepam or 10 mg temazepam. PMID- 2883821 TI - Insomnia in general practice: the role of temazepam and a comparison with zopiclone. AB - The aetiology of insomnia can be conveniently divided into six groups: physical (pain, cough, etc.), physiological (shift-workers etc.), psychological (life events), psychiatric (depression, anxiety, etc.), iatrogenic (stimulant drugs, etc.) and idiopathic (no obvious cause). The four main types of insomnia are: prolonged latency, frequent short awakenings, one or two long awakenings and early morning awakening. Patients' habits that may interfere with sleep are related to: alcohol, smoking, tea and coffee drinking, and bedtime drinks. In a double-blind comparison between temazepam and nitrazepam, both drugs were shown to be effective hypnotics, nitrazepam being better for early morning wakening, although at the expense of more hangover effects. Zopiclone, a new cyclopyrrolone hypnotic, was also compared to temazepam in a double-blind cross-over trial and similar hypnotic effects were recorded with both drugs. PMID- 2883823 TI - The use of oral benzodiazepines as premedications: the usefulness of temazepam. AB - The primary aim of premedication is to relieve the patient's anxiety/restlessness before anaesthesia and to ensure optimum quantity and quality of sleep on the night preceding surgery. With these objectives in mind, oral benzodiazepines offer a good alternative to traditional parenteral premedicants, especially as the clear anxiolytic and sedative effects of the former are of great clinical value. Oral temazepam has proven to be a valuable premedicant given on the evening before operation and/or the following morning, before surgery. Administered as a sedative in a single 20 mg oral dose the night before surgery, temazepam provided a good night's sleep in 77 percent of gynaecological surgical patients; patients slept for 7.6 hours and had no significant residual effects. As a premedicant, temazepam was as effective as parenteral diazepam or papaveretum. Temazepam's short duration of action facilitates rapid postoperative recovery in children, adults, and in the elderly. Thus, it is indicated especially for short operative procedures when rapid recovery and swift return to fitness are essential. PMID- 2883824 TI - The use of temazepam Expidet (FDDF) as a premedicant in children. AB - One hundred and forty-nine children were given a novel oral presentation (FDDF) of temazepam as pre-operative medication. The high degree of acceptability by the child, the short duration of onset and resulting percentage production of satisfactory demeanour in the anaesthetic room, suggest that temazepam would make a very useful addition to the paediatric premedicant armamentarium. PMID- 2883825 TI - Pharmacokinetics of temazepam compared with other benzodiazepine hypnotics--some clinical consequences. AB - When the various benzodiazepine hypnotics are studied, large differences are seen with regard to their pharmacokinetic properties and metabolism in man. Some are eliminated from the body at a relatively slow rate (e.g. nitrazepam), others are metabolized rather rapidly (temazepam, triazolam). Some benzodiazepine hypnotics have major active metabolites that are slowly eliminated (flurazepam, quazepam), while others have non-active metabolites (temazepam, lormetazepam). In hypnotic treatment, the duration of drug action should be restricted to the duration of the night, hence a compound with a relatively short elimination half-life may represent a more rational choice. An overview is given of the pharmacokinetics of the currently available benzodiazepine hypnotics with emphasis on temazepam and other hydroxylated benzodiazepines. PMID- 2883826 TI - Benzodiazepine hypnotic metabolism: drug interactions and clinical implications. AB - Benzodiazepines are the drugs of choice when initiating hypnotic therapy. Though the mechanism of benzodiazepine action in the central nervous system is similar for all drugs in this class, differences in absorption and pathway of elimination are associated with differences in observed clinical effect. After single-dose administration, onset of hypnotic effect is most closely related to rate of drug absorption and duration of effect is more closely associated with extent of drug distribution. Relative affinity of the individual benzodiazepine for the specific central nervous system binding site may also determine duration of action. During multiple-dose chronic therapy, route of metabolic biotransformation and elimination half-life assume more importance. An increased incidence of adverse drug effects due to high doses of accumulating benzodiazepines may be seen in the elderly and patients with central nervous system deficits or chronic liver disease. Benzodiazepine metabolic biotransformation and clearance is broken into three groups. Group 1--oxidative biotransformation; Group 2--high clearance drugs; Group 3--drug conjugation. Groups 1 and 2 are implicated in a number of drug-disease and drug-drug interactions. Group 3 drugs have little change in patients with liver disease or when administered with inhibitors of drug biotransformation. Clinical implications of these metabolic interactions are variable, but inhibition of Group 1 and 2 benzodiazepine clearance has been associated with increased sedation and psychomotor impairment. PMID- 2883827 TI - Normal sleep, disturbed sleep, transient and persistent insomnia. AB - There are three fundamental principles for understanding sleep; the sleeping brain is not a resting brain, the sleeping brain functions in a different manner from the waking brain and the activity and work of the sleeping brain are purposeful. The sleeping brain does fail and this failure is manifest in a variety of clinical symptoms; all sleep complaints should be taken seriously and investigated. Transient insomnia is uniformly associated with objective sleep disturbances which have been documented following phase shifts of the major sleep period such as that caused by transmeridian travel. However, the degree to which the individual responds to these factors is variable. There is a consensus that sleep medications are indicated for transient and short-term insomnia. Benzodiazepine hypnotics are commonly used to induce and maintain sleep, and improve daytime alertness. PMID- 2883828 TI - Psychopharmacological aspects of idiopathic and transient insomnia. AB - Residual sedative effects seem to be intrinsic properties of effective hypnotic agents. Residual effects are dose related and more likely if the elimination half life is greater than 12 hours. In two separate studies, investigations into effects on performance were carried out using a series of psychometric tests. In the first, a group of skilled radar operators working a shift system were given a pre-sleep administration of temazepam 20 mg and measurements were made of any residual effects. In the second clinical study, general practice patients suffering from idiopathic insomnia were randomized onto either temazepam 20 mg, triazolam 0.25 mg, nitrazepam 5 mg, flurazepam 15 mg, or placebo. Assessments were made using the Leeds Psychomotor Tester to measure Choice Reaction Time and Critical Flicker Fusion. In a separate test, digit substitution was used to measure sensory processing ability. In addition, the Leeds Sleep Evaluation Questionnaire was completed by each patient in the clinical study to provide a subjective evaluation of ease of getting to sleep, ease of awakening and behaviour after awakening. Neither study showed a residual activity that was likely to impair performance following temazepam 20 mg indicating the usefulness of this drug in the management of idiopathic insomnia and sleep difficulties introduced by changes in scheduling of sleep, i.e. intercontinental travel or shift work. PMID- 2883829 TI - Hypnotics and transient insomnia. AB - An hypnotic should be used only when there is evidence of sleep disturbance. The wide range of sleep disorders (e.g. delayed sleep onset or problems of sleep maintenance) and the added complication that the patient may be involved subsequently in skilled work demand that the pharmacokinetics of various hypnotics must be understood before the correct hypnotic can be chosen. Impaired performance is more severe and persists far longer with compounds that are slowly eliminated and with the use of higher doses. The particular situations of aircrew and mountaineers have been studied in detail. Caution must be exercised in the management of aircrew coping with irregularity of rest and work. Temazepam has been used for aircrew for over 10 years and the absence of adverse effects ensures that it remains the recommended hypnotic in this area of medical practice. The relationship of insomnia with the hypoxic environment is undetermined. To investigate this, sleep was studied in six individuals during an expedition to the Himalayas. At altitude, temazepam led to less wakefulness and to drowsy sleep--there were no prolonged sleep latencies. PMID- 2883830 TI - Pharmaco-EEG, behavioural methods and blood levels in the comparison of temazepam and flunitrazepam. AB - In a double-blind placebo-controlled cross-over study, the blood levels and pharmacodynamic properties of temazepam were compared with flunitrazepam using quantitative pharmaco-EEG and psychometric methods in ten healthy volunteers. Computer-assisted spectral analysis of the EEG after three doses of temazepam (10 mg, 20 mg and 40 mg) compared with placebo showed statistically significant changes in brain function. These changes were also seen after the administration of the reference drug (flunitrazepam 2 mg) and are typical of anxiolytic sedatives. Psychometric and psychophysiological tests demonstrated significant alterations at the behavioural level, especially after higher doses of temazepam and 2 mg flunitrazepam, as expected. However, low doses or low blood levels of temazepam induced an improvement of performance in certain variables. Dose efficacy calculations identified 2 mg flunitrazepam and 40 mg temazepam as the most CNS-effective, followed by 20 mg and 10 mg temazepam, while the least changes occurred after placebo. Time-efficacy calculations showed marked inter drug differences. The pharmacodynamics of both drugs parallel their respective pharmacokinetics. Regression and correlation analyses between blood levels and EEG or psychometric changes revealed that beta activity and the centroid of the EEG were positively correlated with plasma levels, while alpha activity, psychometric variables and skin conductance were negatively correlated. Psychometric variables started to deteriorate above a blood level of approximately 250 ng/ml, while below this level an improvement was seen. Such (sedative) blood levels were only reached after doses higher than 10 mg temazepam. Our findings indicate that 10 mg temazepam has tranquilizing properties, while 20 mg and 40 mg doses exert, in addition, sedative sleep inducing effects. PMID- 2883831 TI - Benzodiazepines in the treatment of sleep disorders: pharmacokinetic aspects. AB - In order to avoid after-effects during the day, slowly eliminated hypnotic agents should not be used in the treatment of sleep disorders. It has become customary to separate long-acting from short-acting benzodiazepines and to use the (terminal) half-life as the principle of classification. This approach is only justified, however, in the case of quickly absorbed benzodiazepines that have no pharmacologically active metabolites and that exhibit one-compartment disposition kinetics. In contrast, the duration of action of benzodiazepines characterized by marked two-compartment disposition kinetics can only be estimated correctly when the potency and all relevant kinetic parameters of the drug preparation and its pharmacologically active metabolites are considered. PMID- 2883832 TI - Systemic and renal hemodynamic effects of single oral doses of cadralazine and long term antihypertensive effects of cadralazine in patients receiving therapy with beta-blockers and diuretics. PMID- 2883833 TI - [Morphometric evaluation of the seminiferous tubule diameter and peritubular fibrosis in cryptorchid patients]. PMID- 2883834 TI - Long-term treatment of chronic pain with acupuncture. Part I. AB - A 5-year trial of acupuncture therapy in the Finnish NHS is surveyed. In total 348 patients attending Halikko Health Centre in SW Finland were treated with needle-stimulation for a wide variety of chronic pain syndromes. The mean number of acupuncture sessions was 5 in the primary series and 41% of patients received more than one series. An analysis of results showed significant relief of pain (more than 40% reduction on the visual analogue scale) in myofascial syndromes affecting the head, neck, shoulder and arm. Osteoarthrosis of major joints, and backache, responded less favourably. In total 65% of those patients who had taken analgesics before acupuncture therapy, either stopped totally or reduced their dose considerably. Those with headache could significantly more often reduce their drug intake than those with arthritis or osteoarthrosis. More results and discussion will be published in part II later in this Journal. PMID- 2883835 TI - Long-term therapeutic effects of electro-acupuncture for chronic neck and shoulder pain--a double blind study. AB - Thirty-seven patients with chronic neck and shoulder pain were treated with a series of electro-acupuncture treatments. All patients had been unresponsive to previous conventional and placebo treatments for their pain. A double blind evaluation of acupuncture results and hypnotic profiles failed to demonstrate any correlation between the two. Twenty-four or 64.9% of our patients obtained significant long term improvement. An increase in regional microcirculation by peripheral sympathetic blockade from electro-acupuncture is thought to be responsible for the tissue healing and subsequent pain relief. PMID- 2883836 TI - Effects of acupuncture needle application upon cutaneous microcirculation of rabbit ear lobe. AB - Microcirculatory effects of the application of an acupuncture needle (32-gauge, silver) to the back, corresponding to Geshu (B17) in human beings, were studied in vivo by microscope, using a transparent ear chamber in conscious rabbits. Although no striking findings were obtained during the needle application for a period of 30 minutes, it was clearly observed that the microvascular blood flow increases gradually in parallel with augmenting spontaneous rhythmic fluctuation of the vessel diameter, namely vasomotion, throughout a continuous observation period longer than 2 hours following release from the needle application. Diameters of arterioles and venules at the full-dilating phases of vasomotion reached levels higher than 200% and 250% of the initial values just before application of the needle, respectively. The clinical efficacy of acupuncture was suggested to be explained at least in part by the increased rhythmic microvascular blood flow in parallel with vasomotion, from the physiological point of view based on the previous investigations. PMID- 2883837 TI - Influence of naloxone on electro-acupuncture analgesia using an experimental dental pain test. Review of possible mechanisms of action. AB - The purpose of this study was to examine in man the analgesic effect of non segmental electroacupuncture (EA) limited to a single point (Hoku hand point) and the influence of naloxone using an original modified electrical dental pain test. Results in the literature are still contradictory as to the degree and specificity of acupuncture analgesia and its opioid nature. Acupuncture techniques as well as experimental pain models are factors accounting for the discrepancies in the results. For this reason, we designed an experimental pain test characterized by a high degree of specificity, validity and reliability. We chose optimal conditions for eliciting specific acupuncture effect, i.e. non segmental, low frequency and painful intensity range. A cross-over repeated measure experimental design was used. Five normal trained subjects participated in 65 sessions under four conditions (control, EA, EA+naloxone, EA+placebo). Changes in experimental dental pain thresholds served as indices of analgesia. The results indicated a 27% pain threshold increase after 30 minutes of EA stimulation (p less than .0001), with no differential effect between pain detection (mild pain sensation) and pain discomfort (strong pain sensation). This increase was partially blocked by the double blind injection of 0.8 mg naloxone IM (p less than .005). The experiment was designed in such a way as to prevent the occurrence of a stress analgesic effect. The endogenous opioid system was shown to be partially involved in acupuncture analgesia. Other mechanisms of action are discussed in view of the literature findings. PMID- 2883838 TI - Meridian-like networks of internal organs, corresponding to traditional Chinese 12 main meridians and their acupuncture points as detected by the "Bi-Digital O Ring Test imaging method": search for the corresponding internal organ of Western medicine for each meridian--Part I. AB - The "Bi-Digital O-Ring Test" imaging method has been successfully used not only to outline the internal organs but also malignant tumors as long as identical reference control tissue is available, regardless of whether it comes from the same individual or others, without exposing the patient to undesirable radiation from X-Rays, strong magnetic field or ultra-sound. While imaging the outline of the internal organs the author found that, from the surface of each organ, lines or networks of lines extend to other parts of the body. Such a line closely resembles well-known lines of meridians of major internal organs in Oriental medicine. This meridian-like network of each internal organ can be imaged using a microscopic slide, dessicated tissue or raw tissue of the same internal organ as reference control substance in "Bi-Digital O-Ring Test" imaging method. In previous papers, among meridians of 12 main internal organs in Traditional Chinese Medicine, the author was able to find which meridian corresponds to which internal organ of Western Medicine as in 10 meridians by "Bi-Digital O-Ring Test" imaging with corresponding internal organs as reference control substances, with the exception of "Pericardium Meridian", and "Triple Burner Meridian". In this study we were able to confirm that the "Pericardium Meridian" can be imaged mainly using adrenal gland as a reference control substance and "Triple Burner Meridian" can be imaged by the ovary or adrenal gland in the female and also can be imaged by the testes or adrenal gland in the male. Thus, the author was able to confirm, for the first time, the corresponding internal organ of Western Medicine for each one of the 12 main meridians. During this study, when actively imaging the meridian-like network, the author found bulging areas of the meridian like network at specific locations, and found that these bulging areas correspond to specific acupuncture points. The area or average diameter of these acupuncture points often increased in the abnormal area and returned relatively small normal diameter by acupuncture given on certain acupuncture points of the same meridian. Thus, one can find the exact location of the meridian-like network and specific acupuncture points along the network. Therefore, it is now possible to re evaluate true effects of giving acupuncture on these specific points as well as some of the other classical concepts of acupuncture. PMID- 2883839 TI - Acupuncture therapy for the treatment of intractable, idiopathic epilepsy in five dogs. AB - Five epileptic dogs, nonresponsive to high levels of anticonvulsants were presented to the acupuncture clinic at the Veterinary Hospital of the University of Pennsylvania for treatment. Acupuncture was performed by placing small gold implants subcutaneously over the calvaria at acupuncture points on the Governing Vessel (GV), Gall Bladder (GB), and Bladder (B) meridians and left in place to provide constant stimulation to the points. Each of the five dogs treated showed a change in seizure patterns following gold implant placement. Two dogs had decreases in seizure frequency with their medication continued as before acupuncture, but they reverted to their previous pattern approximately five months after treatment. Three dogs continued to have decreased numbers of seizures and were maintained on decreased levels of anticonvulsants. PMID- 2883840 TI - Electromagnetism and the revolution in medicine. PMID- 2883842 TI - [Results of treatment following surgical management of complete acromioclavicular joint dislocation (Tossy III injury). Management using ligament sutures and direct transarticular and indirect extra-articular stabilization]. AB - In the last 5 years 36 patients with complete akromioklavikular separation were treated in 21 cases by ligament suture and Balser-plate, in 15 cases by ligament suture and "Zuggurtung". Good and very good results were found in 85%. Patients in which the protection of the ligament suture was given by application of the Hook-plate had better results than those with "Zuggurtung". The use of the Balser plate remarks a safe method in protecting the coracoid-clavicular ligament suture. The rate of complications is rare, compared with the patients in the other group. Functional results seem to be better in comparison to other methods of operative treatment. PMID- 2883843 TI - [Origin, diagnosis and treatment of sternoclavicular joint dislocation]. AB - Traumatic dislocation of the sternoclavicular joint is very uncommon (1,5% of all dislocation, 10% of all dislocations in clavicular joints; ratio acromioclavicular dislocations: sternoclavicular dislocations = 5-10:1). The functional importance of this joint requires open reduction with reconstruction of its ruptured ligaments and the disc. The sternoclavicular joint can be dislocated in association with congential, developmental, degenerative and inflammatory processes (M. Friedrich, rheumatoid arthritis). Epiphyseal separations or fractures of the medial end of the clavicle can usually be treated conservatively, but interposition of the joint capsule between the fragments may cause the dislocation to be irreducible. In addition to clinical examination and anteroposterior of oblique posteroanterior X-rays, tomography, computed tomography and arthrography can be of help in diagnosis. Additional special X-ray pictures as suggested by Heinig, Hobbs and Kattan are very helpful in determining the degree of dislocation (Allman). If open reduction is necessary, the functional importance of the disc and the angle of inclination of the joint socket must be taken into consideration. PMID- 2883841 TI - [Traumatic scapho-lunate dissociation. Functional analysis, surgical therapy and results]. AB - The traumatic scapho-lunate dissociation represents a heavy lesion of the carpal ligaments. The instability and incongruity of the joint causes a considerable loss of the function of the hand. The mechanical situation of the proximal carpal row is demonstrated on the base of anatomical investigations and the mechanism of the accident in a subluxation-rotation injury is shown. The therapeutic consequences are pointed out and the author's own operations procedure (reconstruction of ligaments) with results is presented. PMID- 2883844 TI - [Use of the dynamic hip screw in the management of combined fractures of the femoral shaft and coxal end of the femur]. AB - Treatment of combined fractures of the shaft of the femur and near the hip joint presents special problems. The pattern of these problems is presented on the basis of four cases that had occurred during a six-month period. A useful method for the appropriate treatment of such fractures by surgical means is demonstrated. PMID- 2883845 TI - [Primary plastic reconstruction of a lateral ligament injury of the upper ankle joint]. AB - The article introduces a new aspect in the treatment of ruptures of the lateral ligaments of the ankle. We used the modification of tenodesis according to Castaing and Meunier (3) in the operation of the acute lesions of the fibular ligament. The wearing of a cast for 6-7 weeks after operation is generally not necessary because stability of ankle joint ligaments is obtained. The disadvantages of complete immobilization and trophic changes as well as tenodesis effect are avoided. The patients begin with functional physiotherapy after wound healing (10th postoperative day). Careful extremity loading of the selected, active patient is possible four weeks after operation. 118 reconstructions of the ankle joint ligaments (96 with the abovementioned method) have been performed in the Department of Surgery of Witten-Herdecke University between 1970-1982. Of 43 patients checked in follow-up examination (mean postoperative period three years) 5 showed unsatisfactory balance (tenodesis effect). PMID- 2883846 TI - [Tenography of the peroneal tendon sheath. A means for diagnosing dislocation of the peroneal tendon]. PMID- 2883847 TI - [Significance of "healing instability" of the fracture fissure in fracture healing. Absolutely stable osteosynthesis must not be enforced]. AB - The difficulty inherent in operative osteosynthesis is that for every type and localization an optimal biomechanical constellation must be achieved in the fissure, depending on the physiological tasks and functions to be performed by the bone in question. The authors point out the possible sequels of both excessive stabilization and insufficient stabilization. The compression nail developed from the intramedullary Kuntscher nail has proved its worth as a so called "fixateur interne" for the realization of the dynamic lock principle, not least also because the tissue is hardly injured since the long bone is not "drilled open" and also because the bone remains fully integrated as a weight bearer. PMID- 2883848 TI - The antisecretory profile of action of the H2-receptor antagonists, famotidine, loxtidine, ranitidine and L-643,441 on the rat isolated gastric mucosa. AB - Four H2-receptor antagonists, famotidine, loxtidine, ranitidine and L-643,441 were tested against gastric secretory concentration-response curves to histamine, methacholine and dibutyryl cyclic AMP (dbcAMP) on the rat isolated gastric mucosa. All four drugs inhibited the secretory response to histamine, but the nature of this H2-receptor antagonism differed according to the drug. Ranitidine and famotidine were competitive, fully surmountable antagonists of histamine, but loxtidine and L-643,441 were unsurmountable antagonists. At high concentrations, the H2-receptor antagonists caused a small inhibition of the secretory response to methacholine but had no effect on the secretory response to dbcAMP. The rat isolated gastric mucosa is a useful preparation for characterisation of the antisecretory effects of H2-receptor antagonists. PMID- 2883849 TI - Inhibition of 14C-aminopyrine accumulation in isolated rabbit gastric glands by the H2-receptor antagonist HOE 760 (TZU-0460). AB - Acid secretion in isolated rabbit gastric glands was measured by means of the 14C aminopyrine accumulation technique. Hoe 760 (TZU-0460) and Hoe 062, the desacetylated compound of Hoe 760, caused a concentration-dependent reduction of histamine (100 microM) induced aminopyrine-accumulation. The IC50-values were 3.16 +/- 0.84 microM (n = 5) and 1.58 +/- 0.6 microM (n = 6) for Hoe 760 and Hoe 062, respectively. In comparison an IC50 of 9.0 +/- 0.72 microM (n = 6) was obtained for cimetidine and 3.3 +/- 1.4 microM (n = 5) for ranitidine. The IC50 values of ranitidine, Hoe 760 and Hoe 062 were significantly different (p less than 0.05) from cimetidine. The addition of increasing concentrations of Hoe 760 to the histamine concentration-response curve caused a parallel rightward shift. The transformation of these concentration-response curves according to Arunlakshana and Schild indicated that this inhibition was caused by a competitive antagonism of the histamine receptor on the parietal cell. In agreement with these findings the dbc-AMP stimulated aminopyrine accumulation remained unaffected by the H2-receptor antagonists. PMID- 2883850 TI - Pharmacologic analysis of LY188695 (KB-2413), 1-(2-ethoxyethyl)-2-(4-methyl-1 homopiperazinyl)-benzimidazole difumarate, a potent histamine1 receptor antagonist. AB - LY188695 was evaluated both in vitro and in vivo in the guinea pig to determine its pharmacologic profile. The compound antagonized histamine-induced contractions of ileum, aorta, and trachea with pKB values of 9.9, 9.9, and 9.2 respectively. In the lung parenchymal strip, LY188695 caused a rightward shift of the histamine concentration-response curve with a reduction in the maximal response at all antagonist concentrations tested. The reason for this effect is unknown, but it was not due to a nonspecific depressant action of the compound on the parenchyma. Selectivity was shown by its inactivity against leukotriene D4, bradykinin, prostaglandin F2 alpha, acetylcholine, norepinephrine, and serotonin on various guinea pig and rat smooth muscles. Similarly, H2 receptor-mediated relaxation of the rat uterus was unaltered by LY188695. Increases in total pulmonary impedance caused by i.v. histamine to anesthetized guinea pigs were reduced by as little as 3 micrograms/kg given orally 1 hour prior to histamine challenge. In this system, LY188695 was 15 times more potent than chlorpheniramine and 100 times more potent than terfenadine. Similar responses elicited by acetylcholine were not antagonized by LY188695. A duration of action greater than 4 hours was observed in this model. Ovalbumin given i.v. to sensitized guinea pigs increased total pulmonary impedance which was markedly decreased after oral administration of 30 or 100 micrograms/kg LY188695. These results indicate that LY188695 is a very potent antagonist of H1-mediated responses and suggest that this agent might be useful in disease states characterized by an overproduction of histamine. PMID- 2883851 TI - Comparative polypeptide analysis of human, murine and strigis herpesviruses with murine cytomegalovirus by polyacrylamide gel electrophoresis. AB - The polypeptide composition of five purified murine herpesvirus (MHV) strains grown in a stable line of rabbit embryo fibroblasts (REF) was analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and compared with herpes simplex virus type 1 (HSV-1). About 24 structural polypeptides of molecular mass ranging from 275,000 to 25,000 were identified in MHV and HSV-1. The polypeptide profiles of MHV and HSV-1, showed a close similarity. The polypeptides of MHV were further compared with those of HSV-1, HSV-2, herpes virus strigis (HVS) and murine cytomegalovirus (MCMV). Differences were found between herpesviruses of different origin and MCMV. SDS-PAGE analysis of the six strains of MCMV labelled with 14C-amino acid hydrolysate also revealed differences in electrophor eticprofiles of MHV and MCMV proteins, what was confirmed by densitometric scanning of HSV-1, MHV and MCMV. PMID- 2883852 TI - Effect of (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil on Epstein-Barr virus antigen expression in P3HR-1 cells: comparison with acyclovir. AB - The effect of (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BrVaraU, VaraU) in comparison to 9-(2-hydroxyethoxymethyl)guanine (ACV) on the proliferation of human lymphoblastoid P3HR-1 cells in culture and on the expression of Epstein-Barr virus capsid antigen (VCA) in the same cells was evaluated. After 7 days of cell growth, at 100 mumol/l the total number of new generations in drug-treated cultures was similar or 5 and 10% below that in drug free control cultures, for VaraU, ACV, and BrVaraU, respectively. During the same time the percentage of VCA-expressing cells decreased from 6.3% in drug-free cultures to 1.3, 1.5, and 2.0% in cultures treated with VaraU, ACV and BrVaraU, respectively. In VaraU-treated cultures a further decrease in the percentage of VCA-positive cells down to 0.5% was revealed 7 days after drug removal. VaraU was also effective in reducing the proportion of VCA-expressing cells at 10 and 1 mumol/l. At 14 days after drug removal, the inhibitory effect of ACV was nearly reversed, whereas BrVaraU showed a prolonged VCA- suppressing effect. PMID- 2883853 TI - Varicella-zoster virus IgM antibody fraction separated by minicolumn gel filtration in serodiagnosis of acute infection. AB - Gel filtration through Sephadex G-200 or Ultrogel AcA 34 minicolumns was applied to isolate IgM antibodies from sera of patients with varicella and herpes zoster (HZ). Serum samples were stained with Sudan III and Evan's Blue in order to monitor the separation process visually when running several columns at the same time. The presence of specific IgM antibodies was demonstrated by enzyme linked immunosorbent assay (ELISA). Rapid separation of stained sera by diffusion chromatography on minicolumns with successive determination of specific IgM antibodies in ELISA proved suitable for serological diagnosis of varicella, whereas the significance of IgM-specific antibody response in HZ seems uncertain. PMID- 2883854 TI - Corneal inoculation of murine herpesvirus in mice: the absence of neural spread. AB - Mouse herpesvirus (MHV) - a recently isolated herpesvirus - when inoculated into the right scarified cornea spread to lungs and liver by haematogenous route. Later on, the virus was recovered from lungs, spleen and trigeminal ganglia at intervals up to 8 months post-infection (p.i.). Another mice were infected by intranasal route and examined up to 264 days p.i. In latter case, MHV was recovered from lungs, spleen, kidneys, trigeminal ganglia and brain stem. At late intervals, direct isolation from lungs and spleen was as frequent as recovery of MHV from cultured explants; kidney fragments in culture yielded virus at a slightly enhanced rate, while positive MHV isolations from trigeminal ganglia and brain stem increased considerably after explantation. It is concluded that the persistence of MHV in lungs and spleen was productive with continuous presence of small but detectable amounts of infectious virus. PMID- 2883855 TI - Rotavirus persistence in malabsorption syndrome: virus assessment by immunofluorescence in small intestine biopsies in relation to antibody titres. AB - Results of quantitative immunofluorescence (IF) in small intestine biopsies and the serum antibody titres as detected by indirect Rotalex test in rotavirus infections were compared using regression and correlation analysis. Based on the significance of the statistically established correlation (r = 0.76; n = 30) between immunohistological identification of rotavirus antigen and determination of serum antibody levels, the indirect Rotalex test may be applied as a diagnostic tool to avoid biopsies in productive rotavirus persistence. PMID- 2883856 TI - Persistence of the scrapie agent in glial cells from rat Gasserian ganglion. AB - Persistence of the scrapie agent in glial cell monolayers from rat Gasserian ganglion have been studied by electron microscopy, virologic and histologic methods. Under chosen experimental conditions the scrapie agent had been shown to persist in cells for over 2 years. The infected cells appeared to be infectious for BALB/c mice throughout. Persistence of the scrapie agent was associated with development of a marked proliferative effect with increasing mitotic index of the cells. Changes similar to those observed in the CNS in vivo were found by means of electron microscopy. The decreased number of oncovirus-containing cells seems to indicate the decreased proportion of such cells in the culture infected with scrapie agent. PMID- 2883857 TI - Occurrence and distribution of Hantavirus in wild living mammals in Belgium. AB - Small mammals were screened for the presence of antibodies to Hantaan virus (HTN) and Hantavirus (HV) antigen in Belgium. Antibody and antigen-positive animals were found in different parts of the country. One insectivore and five rodent species were found positive. The highest prevalence of infection was found in the bank vole (Clethrionomys glareolus). A relation between infected animals and wet habitats was observed. It was obvious that in bank vole the likelihood of infection increased with age. PMID- 2883858 TI - Electron microscopic analysis of in vitro interaction of Rickettsia prowazekii with guinea pig macrophages. I. Macrophages from nonimmune animals. AB - Monolayer cultures of peritoneal macrophages of intact guinea pigs were infected with Rickettsia prowazekii (strain Breinl) and examined by electron microscopy after 30 min, 4 and 24 hr post-infection (p.i.). Three parallel processes developed in infected macrophages: reproduction of rickettsiae in macrophage cytoplasm, destruction in phagolysosomes and production of spheroplast-like forms. Reproduction of rickettsiae yielded 2 cell types: those with dense and with light cytoplasm; they were located side by side in the microcolony and seemed to have a common capsule-like coat. Relatively small spheroplast-like forms of about 1 micron in size were regularly detected. Addition of immune serum to macrophages increased the number of rickettsiae, both of rod-shaped as well as of spheroplast-like ones located within phagosomes, but elicited no increase in the number of digested pathogen cells. PMID- 2883859 TI - Electron microscopic analysis of in vitro interaction of Rickettsia prowazekii with guinea pig macrophages. II. Macrophages from immune animals. AB - Alike to macrophages from intact animals, reproduction, destruction and formation of spheroplast-like forms were observed in macrophages from immune guinea pigs 2 months post-infection (p.i.) with the virulent Breinl strain of Rickettsia prowazekii. Unlike to the former, immune macrophages revealed phagolysosomes which were larger in size and contained more rickettsiae showing morphologic signs of destruction. Spheroplast-like forms occurred more often and were more numerous than in intact animals. Structures morphologically similar to L-forms of gram-negative bacteria and that of chlamydiae were also detected. After adding immune serum, more intact rickettsiae and spheroplasts were found in phagosomes as well as more phagolysosomes contained rickettsiae and spheroplasts with morphologic signs of destruction. It is suggested that clearance of immune macrophages from rickettsiae is mediated by at least two processes: on one hand by destruction of rod-shaped rickettsiae within phagolysosomes and, on the other hand, by formation and subsequent destruction of spheroplast-like forms within vacuoles, which probably also function as phagolysosomes. PMID- 2883860 TI - Experimental double infection with Coxiella burnetii and tick-borne encephalitis virus in Dermacentor reticulatus ticks. AB - Experimental parenteral inoculation of Dermacentor reticulatus ticks with the rickettsia Coxiella burnetii (C.b.) and tick-borne encephalitis (TBE) virus resulted in a generalized rickettsial and viral infection, irrespective of whether the agents were given simultaneously or by a 7 days interval apart. Both agents multiplied intensively in ticks, C.b. being detectable predominantly in cytoplasmic vacuoles and TBE virus mostly in the endoplasmic reticulum. PMID- 2883862 TI - Infection of the central nervous system of mice by standard Sendai virus, defective interfering Sendai virus and the mixture of both: comparison of virus multiplication and pathogenicity. AB - The intracerebral (i.c.) infection of newborn mice with standard Sendai virus (SV), defective interfering Sendai virus (DV) and their mixture (SV + DV) has been used as a model for the possible role of defective interfering particles of paramyxoviruses in several chronic degenerative diseases of central nervous system (CNS). The dynamics of Sendai virus multiplication and virus distribution in CNS of mice, as well as the histological changes and the clinical symptoms were evaluated for up to 112 days post-infection (p.i.). The infectious virus was detected in the brains of animals inoculated i.c. either with SV, or DV, or SV + DV as soon as by 5 hr p.i., with maximum infectivity titre at 24 hr p.i. In brains of animals inoculated with SV, the virus was detected until 5th day p.i.; nevertheless in those, inoculated with SV + DV or DV, low infectious titres could be detected even at later intervals. In mice inoculated i.c. with DV, traces of Sendai virus were detected in subpassages, as late as 3 months p.i. PMID- 2883861 TI - Involvement of prostaglandins in immunosuppression caused by adenovirus in mice. AB - The effect of intraperitoneally (i.p.) inoculated human adenovirus type 6 (Ad6) was tested for humoral immune response against sheep red blood cells (SRBC) in normal and indomethacin-treated mice, with the aim to elucidate the mode of the virus action in immunosuppression. The results indicate that inhibition of prostaglandin synthesis slightly influences the immunosuppressive effect of the virus. It is very likely that also other mechanisms are involved in the immunosuppression observed. PMID- 2883863 TI - Polyester film as an advantageous tool for light and ultrastructural examination of single cells infected with viruses. AB - The use of marked transparent polyester film as a support of cell monolayer, smears or sections (cryostat or paraffin), makes possible to examine the same cell preselected in the light microscope by electron microscope (EM). Consequently, this technique enables to use histological or immunohistological investigations (using immunofluorescence or peroxidase (Px) labelling) by light microscopy before examination in EM. As example we used herpes simplex virus (HSV) type 1-infected cells grown on the above mentioned polyester film. Visualization of the antigen with hyperimmune serum and Px-labelled antiserum was followed by examination of selected cells in EM, where viral particles were clearly visible. PMID- 2883864 TI - Junin virus persistence in mice. AB - Newborn mice surviving intracerebral infection with Junin virus (JV) strain XJ showed viral persistence in brain up to 140 days post-infection (p.i.). Mild meningoencephalitis or encephalitis, but not the neutralizing antibody titres (NtAb) correlated with virus presence. PMID- 2883865 TI - A new subtype ("Brezova") of Tribec orbivirus (Kemerovo group) isolated from Ixodes ricinus males in Czechoslovakia. PMID- 2883866 TI - Influence of beta 2-adrenoceptor stimulation and blockade on cardiac electrophysiologic properties and serum potassium concentration in the anesthetized dog. AB - The influence of selective beta 2-adrenoceptor stimulation and blockade on cardiac electrophysiologic properties was studied in 18 anesthetized dogs. Selective beta 2-adrenoceptor activation by salbutamol failed to alter myocardia excitability but significantly lowered serum potassium concentration. Excitability, refractoriness, and ventricular fibrillation threshold were also not changed after administration of 100 and 200 micrograms/kg of the selective beta 2-antagonist ICI 118,551. However, at a dose of 500 micrograms/kg, refractoriness was prolonged and ventricular fibrillation threshold increased. These changes appear to be due to blockade of beta 1-adrenoceptors rather than to membrane stabilizing effects, since in catecholamine-depleted animals even the highest dose of ICI 118,551 did not alter myocardial electrical properties. It is concluded that beta 2-adrenoceptors do not influence electrophysiologic properties of the canine myocardium. PMID- 2883868 TI - Takayasu's arteritis and myocardial dysfunction. PMID- 2883867 TI - Clinical differences between beta-adrenergic blocking agents: implications for therapeutic substitution. AB - The beta blockers exhibit clinically significant differences in beta-receptor selectivity, intrinsic sympathomimetic activity, and alpha-adrenergic blocking activity. These agents also show important differences in their pharmacokinetic profiles, including gastrointestinal absorption, first-pass hepatic metabolism, lipid solubility, protein binding, hepatic biotransformation, pharmacologic activity of metabolites, and renal clearance of unchanged drug and metabolites. These many differences determine the appropriateness of administering a given beta blocker in a given clinical situation. The selection of beta blockers must also take into account concurrent therapy with other agents. Concurrent administration of beta blockers with drugs that alter gastric, hepatic, or renal function may affect blood levels, duration of action, or efficacy of beta-blocker action. The beta blockers vary in the extent to which their action is altered when they are given with other agents, and therapeutic substitution may produce unwanted side effects and toxicity. Elderly patients should be carefully monitored following interchange among beta blockers, since the probability of drug interaction, impact of adverse effects, unpredictability of response, and physiologic variability of renal and liver function is greater than for younger individuals. Therapeutic substitution among beta blockers in patients already stabilized on a given agent will require careful monitoring. Retitration with the new beta blocker will be required in many cases to assure therapeutic equivalence. Beta blockers are currently used for over 20 medical conditions. There is wide variation in the strength of the clinical evidence supporting the use and efficacy of specific beta blockers for specific conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883869 TI - Systemic and coronary hemodynamic effects of combined alpha- and beta-adrenergic blockade (labetalol) in normotensive patients with stable angina pectoris and positive exercise stress test responses. AB - The systemic and coronary hemodynamic effects of combined alpha- and beta adrenergic blockade produced by labetalol were assessed in 12 normotensive patients with angina pectoris and an ischemic electrocardiographic response to exercise stress. When given to the patient at rest, labetalol (0.5 mg/kg intravenously) produced systemic and coronary vasodilation (mean 16% and 13%, respectively, both p less than 0.05); aortic pressure decreased, cardiac output increased and coronary flow and heart rate did not change. Before labetalol treatment, supine bicycle exercise produced angina in all patients. After treatment, exercise duration was prolonged in 8 patients (average 33%). At the same duration of exercise that led to angina during the control period, ST depression in lead V5 was less after labetalol (from 1.2 to 0.4 mm, p less than 0.5). During exercise, tachycardia was blunted (-12%, p less than 0.05) as were the increases in aortic pressure (-12%, p less than 0.05), left ventricular end diastolic pressure (-7%, difference not significant) and coronary sinus flow ( 16%, p less than 0.05). Cardiac output and systemic and coronary vascular resistance were similar to values during control exercise. The hemodynamic effects of labetalol appeared to be beneficial and differed from those of classic beta-adrenergic blocking agents. PMID- 2883870 TI - Pharmacologic aspects of cardioselectivity in a beta-blocking drug. AB - Beta 2 adrenoceptors have been subdivided into beta 1 and beta 2 receptors, both by the varying response of different tissues to sympathomimetic amines and, more recently, by radioligand-binding techniques. It would appear that beta 1 receptors occur predominantly in the heart, whereas beta 2 receptors are found in lungs, peripheral blood vessels and uterus, and are also involved with glycogenolysis and glucagon and insulin secretion. In addition, the distribution of beta 1 receptors appears to relate to the density of sympathetic innervation of an organ or tissue, but tissues without sympathetic innervation are found to contain beta 2 receptors. Thus, beta 1 adrenoceptors may be considered as physiologically innervated receptors mediating responses to neuronally released norepinephrine, and beta 2 receptors as mediating responses to circulating catecholamines, particularly epinephrine. Radioligand-binding studies have also shown that the heart contains beta 2 receptors and the lung beta 1 receptors, but these are in the minority, and their role has not been identified. For many years, cardioselective beta 1-adrenoceptor antagonists have been available. This was considered to be a dose-dependent phenomenon but recent evidence has cast doubt on the concept that cardioselectivity is lost during dose increases within the therapeutic range. Nevertheless, even small doses of cardioselective drugs may show some beta 2-receptor antagonism, and may have adverse effects on patients with obstructive airways disease. Finally, nonselective drugs may result in a diastolic pressor effect in the presence of circulating catecholamines in contrast to the "vascular sparing" seen with cardioselective drugs. PMID- 2883871 TI - Pharmacologic aspects of intrinsic sympathomimetic activity in beta-blocking drugs. AB - The possession of intrinsic sympathomimetic activity (ISA) by a beta-adrenoceptor blocking drug results in a number of different pharmacologic properties. Most profound are the central hemodynamic effects. A drug with a significant degree of ISA results in less of a decrease in heart rate at rest and cardiac output, and, at least partly because of this, less of a decrease in peripheral blood flow. If prevailing sympathetic tone is low enough (e.g., during sleep) and the degree of ISA is sufficient, an increase in heart rate may be seen from an ISA-possessing drug. If the drug possesses beta 2 ISA, then a peripheral vasodilation action from stimulation of beta 2 vasodilator receptors may also be relevant. If high levels of exercise and full dosages of the drugs are used, a beta-blocking drug with ISA produces less of a decrease in heart rate. In asthmatic subjects, the modest beta-stimulant action on bronchial smooth muscle is not important, as these patients are potentially sensitive to any receptor blockade. Isoprenaline responses are inhibited to a similar degree compared with inhibition of exercise tachycardia, by nonselective drugs with and without ISA, whereas beta 1 selective agents produce much less inhibition of isoprenaline-induced tachycardia. A drug with ISA "down regulates" beta receptors; thus, when the drug is withdrawn there is no post-beta-blocking drug hypersensitivity in contrast to agents without ISA. There is evidence that ISA results in less of a disturbance in certain metabolic processes, particularly lipid metabolism and the metabolism of liver-metabolized drugs. PMID- 2883872 TI - Role of cardioselectivity and intrinsic sympathomimetic activity in beta-blocking drugs in cardiovascular disease. AB - The significance of ancillary properties of beta blockers continues to be the focus of considerable clinical investigation. Beta 1-selective blocking agents, such as acebutolol, inhibit cardiac beta 1 receptors, but have less influence on bronchial and vascular beta 2 receptors. Certain beta 1-selective blocking drugs, including acebutolol, have intrinsic sympathomimetic activity (ISA), also termed partial agonist activity. This property produces slight cardiac stimulation, which can be blocked by propranolol. Drugs with mild or moderate ISA have proven to be as clinically effective as beta blockers lacking this property. Additionally, drugs with ISA possess potential therapeutic benefits, particularly for patients with coronary artery disease. The hemodynamic influences of cardioselectivity and ISA on left ventricular function, heart rate, cardiac output, left-sided heart filling pressure and myocardial oxygen consumption in patients with coronary artery disease are now clearly defined. PMID- 2883873 TI - Effect of beta blockers on vascular resistance in systemic hypertension. AB - Over 20 years ago, it was established that beta blockers could reduce high blood pressure. Currently, several beta blockers with different ancillary properties are available. They all have the property of blocking beta 1 receptors but differ from each other in a number of other respects: they may or may not block beta 2 receptors in low doses (beta 1 = receptor selectivity); they may or may not possess varying degrees of partial agonist activity, also known as intrinsic sympathomimetic activity (ISA); they vary in the extent to which they are soluble in fat (lipophilicity). A review of relevant published findings indicates that the effects of beta blockers on cardiac output are not essential for their antihypertensive effect, nor is penetration of these drugs into the brain and cerebrospinal fluid. Reduction in blood pressure during long-term beta blocker therapy is always associated with reduction of total peripheral resistance. Beta blockers with sufficient ISA to prevent cardio-depression, by exerting less negative inotropic and chronotropic effects on the heart, do not cause initial reflex vasoconstriction in response to cardiac beta blockade. Unlike beta blockers devoid of ISA, these agents ultimately reduce blood pressure by lowering the increased vascular resistance in hypertension to below pretreatment values. Recent beta blocker research has revealed a number of ways to manipulate the characteristically elevated vascular resistance in hypertension. Examples of these efforts are the combination of ISA, alpha 1 or alpha 2 receptor blockade and direct vasodilating properties in the enantiomers of a single beta blocker molecule. The practical significance of these developments remains to be established. PMID- 2883874 TI - Beta-adrenergic blocker withdrawal. AB - Abrupt withdrawal of long-term beta-blocker therapy in patients with angina may be associated with unstable angina and myocardial infarction. It appears that an "overshoot" in heart rate from pretreatment values occurs, which increases myocardial oxygen demand. This increase in heart rate may be secondary to increased beta receptor numbers or increased receptor sensitivity. Another possible mechanism for the increased risk of myocardial infarction after beta blocker withdrawal is increased platelet aggregability. Withdrawal reactions may be less severe with beta blockers that have partial agonist activity. In patients undergoing coronary artery bypass surgery, beta-blocker withdrawal reactions have also been observed. Maintenance of beta-blocker therapy on the morning of surgery appears to reduce this risk. Gradual withdrawal regimens in outpatients with angina may be associated with lower risk for a beta-blocker withdrawal reaction. The gradual withdrawal of beta blockers in hypertensive patients requires further study. PMID- 2883875 TI - Molecular and functional properties of beta-adrenergic receptors. AB - The beta-adrenergic receptors from various species have been extensively studied both at the pharmacologic and the structural level. Clinical observations may now be interpreted on the basis of mechanisms of interactions between catecholamines and their membrane receptors, regulation of these receptors by guanyl nucleotide binding proteins and stimulation of cyclic adenosine monophosphate production by adenylate cyclase. PMID- 2883876 TI - Clinical significance of beta 1-selectivity and intrinsic sympathomimetic activity in a beta-adrenergic blocking drug. AB - Almost all beta-adrenergic blockers, regardless of their pharmacologic characteristics, appear to have blood pressure-lowering activity in hypertensive patients. Comparisons between nonselective beta-blocking agents, such as propranolol and nadolol, with beta 1-selective drugs, such as metoprolol, atenolol and acebutolol, have demonstrated close similarities in their antihypertensive effects in patients. Similarly, beta blockers with and without intrinsic sympathomimetic activity (ISA) have comparable antihypertensive effects. However, beta-selective agents may offer some advantages over conventional beta blockers in hypertensive patients with concurrent conditions such as chronic obstructive airways disease, peripheral vascular disease, diabetes and hyperlipidemia. Beta 1-selective drugs are also preferred in diabetic patients receiving hypoglycemic agents because they do not interfere with glycogenolysis. Agents lacking ISA, such as propranolol, acutely increase peripheral resistance. beta blockers with ISA usually lower resistance. ISA may also minimize the bradycardia frequently found in elderly patients. Agents with ISA may protect against the decrease in high density lipoprotein cholesterol and the modest increase in triglycerides noted with some beta blockers that do not have ISA. Thus, in a large number of clinical situations in which hypertension is found, the properties of beta 1 selectivity and ISA allow beta blockers to be used with greater safety. Therefore, agents possessing both of these properties may be particularly valuable. PMID- 2883877 TI - Role of cardioselectivity and intrinsic sympathomimetic activity in beta-blocking drugs in chronic coronary artery disease. AB - Beta-adrenergic blocking agents with various ancillary properties have been found valuable in the management of patients with hypertension, angina pectoris and atrial and ventricular arrhythmias. They are also used to reduce the risk of a subsequent coronary event after a myocardial infarction. In approximately 2 decades, the role of these agents in the patient with angina pectoris has expanded from one primarily involving the adjunctive treatment of the patient refractory to other drugs, to the present, in which beta-adrenergic blockers are the most common prophylactic agent prescribed for this indication. PMID- 2883878 TI - Impact of beta 1 selectivity and intrinsic sympathomimetic activity on potential unwanted noncardiovascular effects of beta blockers. AB - Beta-adrenoceptor-blocking drugs are widely used as effective antihypertensive and antianginal agents, but treatment with these agents may be contraindicated in hypertensive patients in whom receptor blockade would interfere with noncardiovascular activities dependent on sympathetic drive. beta blockade impairs pulmonary function in asthmatic patients through antagonism of beta 2 bronchodilation. However, patients with chest problems may be treated effectively with beta 1-selective drugs, including acebutolol, atenolol and metoprolol. The metabolic response to hypoglycemia, which is mediated by beta-receptor stimulation, involves insulin release, gluconeogenesis, tachycardia and increased systolic pressure. Beta 1-selective drugs are preferred in patients who need to increase blood glucose levels because they do not interfere with glycogenolysis. Hypertension induced by pregnancy may be treated with a beta blocker with no apparent adverse effects on the fetus or neonate. Those possessing intrinsic sympathomimetic activity may be preferable. PMID- 2883879 TI - Effects of beta blockers and other antihypertensive drugs on cardiovascular risk. AB - The treatment of high blood pressure with beta-blocking and other antihypertensive agents has been associated with a decrease in the incidence of stroke, progression of hypertension, heart failure, left ventricular hypertrophy, retinopathy and renal failure. Although hypertension increases the risk for developing coronary disease, the risk is heightened markedly if coexistent hyperlipidemia, smoking or glucose tolerance is present. Thiazide diuretics, primarily used as antihypertensive agents, compromise glucose tolerance and are associated with increases in plasma cholesterol, triglycerides and low density lipoprotein levels. Nonselective and beta 1-selective beta blockers have also been associated with increases in plasma triglycerides and very low density lipoproteins, as well as with decreases in high density lipoprotein levels. The effects of various antihypertensive agents on lipid levels, lipid metabolism, carbohydrate metabolism, left ventricular size and atherogenesis are discussed. PMID- 2883881 TI - Suicide in a patient with undiagnosed periarteritis nodosa. AB - Surveys of medical examiners' records have shown that as many as one-third of suicide victims have serious physical illnesses. We report the case of a 56-year old woman who committed suicide by drug overdose. At autopsy, she had severe widespread periarteritis nodosa, which had been unsuspected during life. The identification of treatable physical illness in suicide victims is important in suicide prevention, yet such illness may be overlooked after death unless a forensic autopsy is performed. PMID- 2883880 TI - Patterns of calling time and ipecac availability among poison center callers. AB - Over a one-month period all telephone calls from the public (n = 3828) to a regional poison center were analyzed. The proportion of early calls (within ten minutes of exposure) decreased with age. Late calls (greater than 30 minutes) were significantly associated with higher hospital referral rates when compared with earlier calls in children younger than 5 years (4.6% vs 1.8%) and adults (33% vs 15%). Ipecac was available in 59% of the homes of callers with children younger than 5 years. Hospital referrals were significantly less common among children who had ipecac at home (1%) compared with children who did not (3%). While the availability of ipecac was similar among callers and a matched sample of households who previously called the poison center (58%), ipecac was much less frequently available (24%) among households whose members had not previously called the center. These data infer that educating the public to call the poison center promptly may result in reduction of hospital referrals. Poison education efforts should be targeted to populations with low ipecac availability and low utilization of the poison center. PMID- 2883882 TI - Altered concentrations of gastrin-releasing polypeptide and somatostatin in fundic and duodenal bulb mucosa of patients with duodenal ulcer disease. AB - The concentrations of gastrin-releasing polypeptide, somatostatin (SS), and gastrin in extracts of endoscopically obtained biopsies from the fundus, antrum, and duodenum of patients with uncomplicated bile stones (controls) or duodenal ulcer disease were measured with specific radioimmunoassays. The validity of the tissue sampling was confirmed by characteristic and significant differences between gastrin concentrations at the different biopsy sites. Gastrin-releasing polypeptide levels were at their highest in the fundic and duodenal bulb compared to the antrum in controls (p less than 0.01), whereas no differences in gastrin releasing polypeptide content of the different parts of the stomach were found in duodenal ulcer patients. Compared to controls gastrin-releasing polypeptide in duodenal ulcer patients was reduced in fundic and duodenal bulb mucosa (p less than 0.01). SS levels were highest (p less than 0.05) in the first part of duodenum in controls. Compared to controls duodenal ulcer patients had lower SS concentrations present in fundic (p less than 0.01) and highest SS concentrations present in duodenal bulb mucosa (p less than 0.01). There was no correlation between acid secretion and mucosal gastrin-releasing polypeptide or SS concentrations in any part of the stomach and duodenum. PMID- 2883883 TI - Effect of famotidine on hepatic hemodynamics and peptic ulcer. AB - The acute effects of histamine H2 receptor antagonist, famotidine, on hepatic hemodynamics were studied in six normal volunteers and eight patients with chronic liver disease, and its chronic effects on peptic ulcer, portal hemodynamics, and hepatic function were studied in 20 patients with chronic liver disease and peptic ulcer (16 with gastric ulcer, four with duodenal ulcer). Infusion of 20 mg famotidine did not reduce hepatic blood flow and portal blood flow in normal subjects, nor did it reduce cardiac output, the gradient between wedged hepatic vein pressure and free hepatic vein pressure, hepatic blood flow, and portal blood flow in patients with chronic liver disease. An oral dose of 20 mg famotidine twice daily for 2 months healed peptic ulcer in 19 of 20 patients (95%) with chronic liver disease and peptic ulcer, without any change in portal blood flow and hepatic function. Thus famotidine does not appear to alter hepatic hemodynamics and hepatic function in normal subjects and patients with chronic liver disease. PMID- 2883884 TI - 1986 Stuart distinguished lecture. The "natural history" of inflammatory bowel disease and therapeutic decisions. PMID- 2883885 TI - Famotidine. The ACG Committee on FDA-Related Matters with primary authorship by G. Friedman. American College of Gastroenterology. AB - Famotidine is a potent H2 receptor antagonist containing a thiazole ring structure, thus differing chemically from cimetidine and ranitidine. Pharmacologically, famotidine is nine times more potent than ranitidine and 32 times more potent than cimetidine. In the Zollinger-Ellison syndrome famotidine is more potent than cimetidine or ranitidine and has a 30% longer duration of action. Randomized double-blind controlled duodenal ulcer studies reveal famotidine effectively heals active ulcers when compared to placebo and that healing rates are comparable to those seen at 8 wk with ranitidine. Famotidine effectively heals gastric ulcers in 8 wk when compared to placebo. The drug also significantly reduced the recurrence rate of duodenal ulcers in a 6-month controlled trial. Famotidine is a potent H2 antagonist which appears to be safe at high doses, does not cause antiandrogen side effects, and does not interfere with hepatic oxidative metabolism. Further clinical experience will define famotidine's place in the therapeutic armamentarium against peptic ulcer disease. PMID- 2883887 TI - Multipoint linkage analysis of loci in the proximal long arm of the human X chromosome: application to mapping the choroideremia locus. AB - Choroideremia (McK30310), an X-linked retinal dystrophy, causes progressive night blindness, visual field constriction, and eventual central blindness in affected males by the third to fourth decade of life. The biochemical basis of the disease is unknown, and prenatal diagnosis is not available. Subregional localization of the choroideremia locus to Xq13-22 was accomplished initially by linkage to two restriction-fragment-length polymorphisms (RFLPs), DXYS1 (Xq13-q21.1) and DXS3 (Xq21.3-22). We have now extended our linkage analysis to 12 families using nine RFLP markers between Xp11.3 and Xq26. Recombination frequencies of 0%-4% were found between choroideremia and five markers (PGK, DXS3, DXYS12, DXS72, and DXYS1) located in Xq13-22. The families were also used to measure recombination frequencies between RFLP loci to provide parameters for the program LINKMAP. Multipoint analysis with LINKMAP provided overwhelming evidence for placing the choroideremia locus within the region bounded by DXS1 (Xq11-13) and DXS17 (Xq21.3 q22). At a finer level of resolution, multipoint analysis suggested that the choroideremia locus was proximal to DXS3 (384:1 odds) rather than distal to it. Data were insufficient, however, to distinguish between a gene order that puts choroideremia between DXS3 and DXYS1 and one that places choroideremia proximal to both RFLP loci. These results provide linkage mapping of choroideremia and RFLP loci in this region that will be of use for further genetic studies as well as for clinical applications in this and other human diseases. PMID- 2883886 TI - Congenital adrenal hypoplasia, myopathy, and glycerol kinase deficiency: molecular genetic evidence for deletions. AB - Glycerol kinase deficiency (GKD) is an X-linked recessive trait that occurs in association with congenital adrenal hypoplasia (AH) and developmental delay with or without congenital dystrophic myopathy. Several such patients have recently been reported to have cytological deletions of chromosome region Xp21 and/or of DNA markers that map near the locus for Duchenne muscular dystrophy (DMD) in band Xp21. We have examined the initial family reported in the literature and, using prometaphase chromosome studies and Southern blot analysis with 13 different DNA probes derived from band Xp21, have found no deletions within this region of the X chromosome. When DNA samples from six other unrelated affected males were analyzed, four of them were found to have different-size deletions within Xp21. Thus, the form of GKD associated with AH and dystrophic myopathy exhibits significant genetic heterogeneity at the DNA level. No deletions were detected in two patients with isolated GK deficiency. Comparison of our molecular studies of unrelated patients with deletions of DNA segments allows us to define the region of Xp21 (between probes J-Bir and L1.4) that most likely contains the genes for GKD and AH. This location is distal to the DMD locus. The patients with progressive muscular dystrophy tended to have larger deletions that include markers known to derive from the DMD locus, while GKD/AH/dystrophic-myopathy patients without current evidence of deletion seemed to have a milder, nonprogressive form of congenital myopathy. PMID- 2883888 TI - Efficient isolation of X chromosome-specific single-copy probes from a cosmid library of a human X/hamster hybrid-cell line: mapping of new probes close to the locus for X-linked mental retardation. AB - We isolated X-chromosomal DNA probes from a cosmid library constructed from a single human X/hamster hybrid-cell line (C12D). One hundred human clones were isolated and used to construct a pool of X-chromosomal DNA. This DNA was digested into 0.15-2-kb fragments and subcloned into plasmids allowing the rapid characterization of new single-copy probes. These were regionally mapped and used for the detection of restriction-site polymorphisms. Together with a series of subcloned probes from individually isolated cosmids, we found seven polymorphic probes among 53 tested. Thirty-one of the probes were physically localized to different regions of the X chromosome. Four polymorphic probes map to Xq27-Xq28: DXS102 (cX38.1), DXS105(cX55.7), DXS107(cpX234), and DXS134(cpX67). These were genetically mapped by multipoint analysis relative to previously characterized loci, a mapping that resulted in the following order: DXYS1, DXS107, DXS51/DXS102, F9, DXS105, Fra-X, F8/DXS52, DXS15, DXS134. The mapping of DXS105 between F9 and Fra-X makes this probe useful for Fra-X analysis. For the linkage between FraX and DXS105, a maximum lod score of 5.01 at 4 cMorgans has been obtained in one large Dutch pedigree. PMID- 2883889 TI - An efficient strategy for gene mapping using multipoint linkage analysis: exclusion of the multiple endocrine neoplasia 2A (MEN2A) locus from chromosome 13. AB - Members of four families in which multiple endocrine neoplasia type 2A (MEN-2A) is segregating were typed for seven DNA markers and one red cell enzyme marker on chromosome 13. Close linkage was excluded between the MEN2A locus and each marker locus tested. By means of multipoint analysis and the genetic map of chromosome 13 developed by Leppert et al., MEN2A was excluded from any position between the most proximal marker locus (D13S6) and the most distal marker locus (D13S3) and from within 12 cMorgans outside these two loci, respectively. However, the support of exclusion within an interval was diminished under the assumption of a substantially larger genetic map in females. The strategy of multipoint analysis, which excluded between 1.5 and 2.0 times more chromosome 13 than did two-point analysis, demonstrates the utility of linkage maps in mapping disease genes. PMID- 2883890 TI - Linkage disequilibrium of plasminogen polymorphisms and assignment of the gene to human chromosome 6q26-6q27. AB - Linkage disequilibrium was observed between newly identified DNA polymorphisms and a previously described protein polymorphism for plasminogen. This finding implies that the two types of polymorphisms describe variation at the same locus. The plasminogen gene was mapped to chromosomal bands 6q26-q27 using somatic-cell hybrids and in situ hybridization. Linkage disequilibrium between protein and DNA polymorphisms has utility in substituting for protein typing in instances where only DNA samples are available, such as from deceased individuals or extinct species. The technique may be useful when cross-hybridizing sequences make the interpretation of Southern blot patterns difficult and may obviate the need for extensive DNA sequencing. In some cases, disequilibrium may provide information useful for determining the appropriate direction for chromosome walks from a marker locus to a target locus. PMID- 2883891 TI - The polymorphic locus for glycogen storage disease VI (liver glycogen phosphorylase) maps to chromosome 14. AB - Human liver glycogen phosphorylase deficiency, also known as glycogen storage disease type VI (GSD VI) or Hers disease, is characterized by hepatomegaly and reduced or absent glycogenolytic response to the injection of glucagon. The recently isolated cDNA encoding the liver isozyme of glycogen phosphorylase was used to map the gene and identify restriction-fragment polymorphisms in normal Caucasians as a prerequisite for detecting linked GSD VI abnormalities. Results of restriction-enzyme analysis using a downstream fragment of the liver glycogen phosphorylase cDNA indicated the existence of a single gene copy per haploid genome. Hybridization of this downstream liver phosphorylase probe to dual laser excited, sorted human chromosomes localized the gene to human chromosome 14. When the downstream probe was tested on genomic DNA cut with seven different restriction enzymes, a single MspI restriction-fragment-length polymorphism (RFLP) was observed in a single individual. In contrast, similar Southern blots performed with an upstream portion of the cDNA encoding liver phosphorylase revealed common RFLPs for four of eight enzymes tested, with minor polymorphic allele frequencies ranging from 33% to 44%. One of the four enzymes (TaqI) revealed two independent polymorphisms. If random distribution of these haplotypes among normal and disease loci, is assumed, approximately 92% of fetuses at risk for Hers disease will be informative when tested with the upstream liver phosphorylase probe. PMID- 2883892 TI - Nonrandom loss of maternal chromosome 11 alleles in Wilms tumors. AB - A series of gene probes for chromosome 11 has been used to study the genetic events associated with the development of Wilms tumor. Examination of DNA samples from five patients with Wilms tumor in whom the tumors showed loss of chromosome 11 alleles and their parents indicate that alleles lost in the tumors are of maternal origin. These data suggest that the parental derivation of chromosome 11 alleles lost in these Wilms tumors is not random. PMID- 2883893 TI - DNA polymorphisms in and around the Apo-A1-CIII genes and genetic hyperlipidemias. AB - We have studied the frequency of DNA polymorphisms in and around the apolipoprotein A-1 (Apo-A1) and apolipoprotein CIII (Apo-CIII) gene loci in 53 persons of Caucasian descent with genetic hyperlipidemias. Three restriction fragment-length polymorphisms (RFLPs) have previously been located 5' and 3' to the Apo-A1 gene and in the Apo-CIII gene and were detected after digestion with XmnI, PstI, and SstI, respectively, and hybridization with a 2.2-kb fragment of the Apo-A1 gene. These RFLPs are in linkage equilibrium. The rare variant sites for XmnI (X2) and SstI (S2) were more frequent in familial combined hyperlipidemia (FCH) than in controls and persons with other genetic hyperlipidemias. When considered as a haplotype, this difference was significant (P less than .03). The findings in this study suggest that the previously reported association between S2 and hypertriglyceridemia may be accounted for, in part, by inclusion of numerous patients with FCH. Our data provide further evidence that these RFLPs around and within the Apo-A1/Apo-CIII genes do not participate in unmasking clinical expression in persons with familial dysbetalipoproteinemia. PMID- 2883894 TI - Polynesian origins and affinities: globin gene variants in eastern Polynesia. AB - Analysis of copy number variants of the duplicated alpha-, zeta-, and gamma globin genes in eastern Polynesians revealed a high frequency of both triplicated zeta-gene chromosomes and a specific alpha thalassemia deletion. This deletion and a novel restriction-enzyme-site polymorphism associated with a zeta zeta zeta chromosome are found only in Melanesians and Polynesians. Analysis of alpha globin restriction-enzyme haplotypes indicated further similarities to Melanesians but suggested an additional non-Melanesian genetic component in eastern Polynesia. Several globin gene alleles showed evidence of marked frequency fluctuations due to genetic drift. PMID- 2883895 TI - Systemic vasculitis resembling periarteritis nodosa in the lupus-like syndrome induced by hydralazine. PMID- 2883896 TI - Non-insulin-mediated glucose uptake predominates in postabsorptive dogs. AB - Overall glucose uptake represents the sum of insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU). In this study, we compared the rate of NIMGU in conscious and anesthetized dogs. Rates of glucose disposal were compared in the basal state and during severe insulinopenia after endogenous insulin suppression by high-dose somatostatin (SRIF) infusion. Steady state NIMGU rates were calculated 2 h after commencing SRIF infusion. Three groups of studies were performed: 1) SRIF in conscious dogs; 2) SRIF in anesthetized dogs; and 3) SRIF plus glucagon, also in anesthetized dogs. In all three groups, serum insulin levels were reduced to below assay sensitivity after SRIF infusion. The basal metabolic clearance rate of glucose (MCRg) for each group was 3.8 +/- 0.4, 3.6 +/- 0.3, and 3.6 +/- 0.3 ml X kg-1 X min-1, respectively (P = NS, all groups). Steady-state NIMGU rates were 2.4 +/- 0.2 (conscious), 2.5 +/- 0.1 (anesthetized, SRIF only), and 2.4 +/- 0.1 ml/kg/min (anesthetized, SRIF plus glucagon). Thus, absolute rates of NIMGU expressed as MCRg in conscious and anesthetized animals do not differ and in the three groups studied comprise approximately the same proportion of the basal glucose uptake (approximately 64, approximately 69, and approximately 66%, respectively). We conclude that approximately 66% of basal postabsorptive glucose uptake occurs via NIMGU mechanisms and that this pathway is unaffected by anesthesia and surgery. PMID- 2883898 TI - Effects of bethanechol and the octapeptide of cholecystokinin on colonic smooth muscle in the cat. AB - The aim of this study is to compare the action of the cholinergic agonist, bethanechol, with the action of the octapeptide of cholecystokinin (CCK-OP) on feline circular colonic smooth muscle membrane potential and isometric tension, using the double sucrose gap. Depolarization of the membrane greater than 10 mV by K+ or bethanechol increased tension and spontaneous spike activity. CCK-OP (10(-9) M) depolarized the membrane (6.1 +/- 1.3 mV) without an increase in tension or spike activity. Depolarization of the membrane by increasing [K+]o was associated with a decrease in the membrane resistance. The slow-wave duration (2.3 +/- 0.2 s) was unchanged by administration of K+ or bethanechol but was prolonged after increasing concentrations of CCK-OP. The maximum effect occurred at a 10(-10) M concentration of CCK-OP (4.5 +/- 0.4 s, P less than 0.01). At higher concentrations of CCK-OP (greater than 10(-10) M), the slow-wave pattern became disorganized. Addition of increasing concentrations of [K+]o or bethanechol, but not CCK-OP, stimulated a concentration-dependent increase in the maximum rate of rise (dV/dtmax) of an evoked spike potential. These studies suggest 1) bethanechol decreased the membrane potential without altering the slow wave activity, whereas CCK-OP has a minimal effect on the membrane potential but distorted the slow-wave shape; 2) an increased amplitude of the spike and dV/dtmax of the spike were associated with an increase in phasic contractions after bethanechol or increased [K+]o; 3) the lack of an increase in the spike amplitude and the dV/dtmax to CCK-OP was associated with no increase in phasic contraction. PMID- 2883899 TI - Supersensitivity to NE alters renal function of chronically denervated rat kidneys. AB - The effect of norepinephrine (NE) infusion (10, 100, and 330 ng/min, iv) on renal blood flow (RBF), glomerular filtration rate (GFR), urine flow, and sodium excretion was studied during ganglionic blockade in Inactin-anesthetized Wistar rats with one kidney innervated and the contralateral kidney denervated 7-10 days before the experiment. During the NE infusions, steady-state mean arterial pressure was 73 +/- 3, 91 +/- 5, and 117 +/- 2 mmHg, whereas plasma NE concentration averaged 3.9 +/- 1.2, 26.4 +/- 3.2, and 78.1 +/- 4.8 pmol/ml, respectively. At the lowest dose, RBF and GFR were decreased significantly in both kidneys but were significantly lower in the denervated kidneys than in the innervated kidneys. Urine flow and total and fractional sodium excretion increased significantly from the innervated kidneys but not from the denervated kidneys during the 100 and 330 ng/min infusion of NE. When renal perfusion pressure was controlled at the level found after ganglionic blockade, RBF and GFR decreased significantly in both kidneys but to a greater extent in the denervated kidneys at all doses of NE. Urine flow and total and fractional sodium excretion decreased significantly from the denervated kidneys at all doses of NE but decreased from the innervated kidneys only at the highest dose. These results indicate that in chronically denervated kidneys both tubular and vascular responses to NE are altered. The data support the conclusion that denervation supersensitivity can significantly alter renal responses to increased plasma concentration of NE. PMID- 2883897 TI - Reflex gastric relaxation in response to distention of the duodenum. AB - Using a newly developed gastric barostat, we studied the effect of duodenal distention on gastric tone in a chronic canine model. In the conscious, fasted dogs, duodenal distention for 15 s consistently induced a marked gastric relaxation (delta intragastric volume = 226 +/- 23 ml). This response could be induced repeatedly without evidence of fatigue. Neither bethanechol nor combined phentolamine and propranolol infused intravenously had any significant effect on gastric relaxation in response to duodenal distention. To investigate the pathway of this duodenogastric mechanism, in four dogs we isolated the vagal nerves at the supradiaphragmatic level within an implanted cooling jacket. During intravenous infusion of bethanechol (used as a cholinergic background to maintain base-line gastric tone), supradiaphragmatic vagal blockade by cooling abolished the gastric relaxatory response to duodenal distention (delta intragastric volume = 11 +/- 5 ml during vagal blockade vs. 194 +/- 36 after vagal rewarming; P less than 0.05). This effect of acute and reversible vagal blockade by cooling was also mimicked by bilateral surgical vagotomy. We conclude that a nonadrenergic, noncholinergic mechanism participates in gastric relaxation induced by duodenal distention. This mechanism is mediated by the vagus nerve. PMID- 2883900 TI - Renal clearance of glutathione measured in rats pretreated with inhibitors of glutathione metabolism. AB - Renal clearance measurements were performed in rats pretreated with various inhibitors of glutathione metabolism. Approximately 97% of the renal gamma glutamyltranspeptidase was inactivated by infusion of AT-125. Within 4.5 h arterial plasma concentration and urinary excretion of glutathione increased from 4 microM and 1.2 nmol/h to 27 microM and 3,900 nmol/h, respectively. The ratio of excreted to filtered glutathione increased from less than 0.01 to 1. When renal glutathione was decreased to 35% of normal by pretreating rats with D,L buthionine-S,R-sulfoximine, the subsequent inactivation of the transpeptidase caused only a two-fold increase in arterial plasma glutathione, and urinary excretion increased to only 70% of the filtered load. The filtered load of glutathione was reduced by intravenous infusion of purified gamma glutamyltranspeptidase. At 1 to 3 h after infusion, arterial glutathione decreased to 0.3 microM. Under these conditions, the amount of glutathione excreted by an AT-125-treated rat was 40-fold greater than the filtered load. When similar experiments were carried out in rats that were pretreated with D,L buthionine-S,R-sulfoximine and AT-125, urinary excretion of glutathione was decreased 10-fold, but it still exceeded the amount filtered. These results firmly establish that apical secretion contributes to the glutathione catabolized in the tubular lumen. PMID- 2883902 TI - Bicuculline blocks an inhibitory baroreflex input to supraoptic vasopressin neurons. AB - The excitability of vasopressin-secreting neurons in the hypothalamic supraoptic nucleus is transiently depressed by an abrupt increase in arterial pressure sufficient to activate peripheral arterial baroreceptors. The present experiments examined the ability of locally applied transmitter antagonists to alter this response. Extracellular data were obtained from 27 supraoptic vasopressin secreting neurons in pentobarbital-anesthetized male Long-Evans rats. In seven of eight cells tested, bicuculline (100 microM) reversibly abolished or delayed the anticipated cessation in neuronal firing that accompanied a 40- to 60-mmHg increase in arterial pressure induced by a brief intravenous infusion of the alpha-agonist metaraminol. Similar tests applied to the remaining cells revealed that prazosin (10 microM), timolol (20 microM), or strychnine (100 microM) were ineffective. These findings suggest that gamma-aminobutyric acidA receptors mediate the depressant responses observed among supraoptic vasopressin-secreting neurons consequent to peripheral baroreceptor activation. PMID- 2883901 TI - Atrial natriuretic peptide increases resistance to venous return in rats. AB - To examine mechanisms by which administration of atrial natriuretic peptide (ANP) decreases venous return, we compared the hemodynamic effects of ANP (0.5 microgram X min-1 X kg-1), furosemide (FU, 10 micrograms X min-1 X kg-1), and hexamethonium (HEX, 0.5 mg X min-1 X kg-1) with those of vehicle (VE) in anesthetized rats. Compared with VE, ANP reduced mean arterial pressure (106 +/- 4 vs. 92 +/- 3 mmHg; P less than 0.05), central venous pressure (0.3 +/- 0.3 vs. 0.7 +/- 0.2 mmHg; P less than 0.01), and cardiac index (215 +/- 12 vs. 174 +/- 10 ml X min-1 X kg-1; P less than 0.05) and increased calculated resistance to venous return (32 +/- 3 vs. 42 +/- 2 mmHg X ml-1 X min X g; P less than 0.01). Mean circulatory filling pressure, distribution of blood flow between splanchnic organs and skeletal muscles, and total peripheral resistance remained unchanged. FU increased urine output similar to that of ANP, yet produced no hemodynamic changes, dissociating diuresis, and decreased cardiac output. HEX lowered arterial pressure through a reduction in total peripheral resistance without altering cardiac output or resistance to venous return. The results confirm previous findings that ANP decreases cardiac output through a reduction in venous return and suggest that this results partly from increased resistance to venous return and not from venodilation or redistribution of blood flow. PMID- 2883903 TI - Convulsions in patients abruptly withdrawn from clonazepam while receiving neuroleptic medication. PMID- 2883904 TI - The prediction of violence in outpatient psychotherapy. AB - This article presents a standard of care for the prediction of violence in outpatient psychotherapy. Major individual and situational correlates of violence are reviewed to provide an actuarial matrix for the further assessment of the patient's intrapsychic experience and interpersonal behavior during the psychotherapy hour. PMID- 2883906 TI - Acute beta-adrenoreceptor blockade and induced hypotension. AB - Thirty patients scheduled for major middle ear surgery and induced hypotension, with a trimetaphan/sodium nitroprusside infusion, were randomly allocated to receive a single oral dose of beta-adrenoreceptor antagonist 2 hours before surgery. In group 1 ten patients received metoprolol 50 mg, in group 2 ten patients received metoprolol 25 mg and in group 3 ten patients received oxprenolol 20 mg. There were ten controls for each group. The nitroprusside infusion rate was significantly reduced in groups 1 and 3. However, there was an unacceptably high incidence of profound bradycardia after induction of anaesthesia in those patients who had received beta-adrenoreceptor antagonists pre-operatively and this technique is not recommended for routine use. PMID- 2883907 TI - Economy in the use of muscle relaxants. Vecuronium after pancuronium. AB - Vecuronium is an intermediate duration, non-depolarising muscle relaxant. When used during prolonged procedures, it may be given by intermittent injection, by continuous infusion or by a single very large dose at the start of anaesthesia. It may also be used to maintain relaxation after the initial use of a long-acting agent, such as pancuronium. This study demonstrates that the effect of a dose of vecuronium used in this fashion is increased when interaction with pancuronium takes place. The clinical and theoretical implications of this observation are discussed. PMID- 2883905 TI - The impact of neuroleptic medication on tardive dyskinesia: a meta-analysis of published studies. AB - To quantify the impact of chronic exposure to neuroleptic medication on the occurrence of tardive dyskinesia (TD), we conducted a meta-analysis of data collected from 21 studies published between 1966 and 1985. The observed prevalence of dyskinesia was greater among exposed subjects in all 21 studies; we estimate that, on the average, the occurrence rate was 2.9 times greater in exposed persons than would be expected if they had been unexposed. We estimate that 65 per cent of exposed cases and 51 per cent of all cases in these investigations were caused by long-term neuroleptic exposure. Among adult United States residents in 1980, we estimate that there were approximately 193,000 neuroleptic-induced TD cases of which about 60 per cent occurred in outpatients. We also observed substantial heterogeneity of effect (rate ratio) across studies, however, partially explained, by changes and differences in the rate of dyskinesia, by differences in the frequency of certain effect modifiers, and by differences in diagnostic methods. Methodologic limitations of the studies and their possible effects on our results are discussed. PMID- 2883908 TI - [Comparative studies of the postoperative phase following opioid analgesia using fentanyl and alfentanil within the scope of extracorporeal shockwave lithotripsy]. AB - 30 patients (ASA Class I-III) received opioid analgesia with fentanyl and alfentanil for extracorporeal shock wave lithotripsy. Average doses were 0.41 mg for fentanyl and 4.14 mg for alfentanil. Blood pressure, respiratory frequency, and blood gases were investigated postoperatively until the 240th min under spontaneous breathing of room air. Blood pressure varied less than 10% from initial values in both groups. The respiratory rate decreased by 13% in the alfentanil group and by 20% in the fentanyl group until the 120th min. The blood gases (paCO2, paO2) showed a slow increase of about 10% in the paCO2 in both groups. The paO2 lay at 5.8% below the baseline after 240 min in the fentanyl group and there was roughly 3% below the baseline after 60 min in the alfentanil group. PMID- 2883909 TI - A method for purification of bacterial R-type lipopolysaccharides (lipooligosaccharides). AB - A new gel filtration method was developed for purification of R-type lipopolysaccharides (lipooligosaccharides) from some nonenteric gram-negative bacteria, including Neisseria meningitidis, Haemophilus influenzae, and Bordetella pertussis. These wild-type lipooligosaccharides are poorly extractable by the phenol-chloroform-ether extraction method of C. Galanos, O. Luderitz, and O. Westphal [1969) Eur. J. Biochem. 9, 245-249) and therefore a new procedure was developed for their isolation. The lipooligosaccharides (LOS) were first extracted by hot phenol-water, treated with RNase, then disaggregated in deoxycholic acid, and purified by gel filtration on Sephadex G-75. By comparison the conventional hot phenol-water purification method using repeated ultracentrifugations yielded less LOS. The yield of LOS by gel filtration was 30 to 108% higher and the purity was better. PMID- 2883910 TI - Development and characterization of a polymer gel with an immobilized enzyme to measure L-glutamate. AB - Glutamate dehydrogenase (GDH) is used in an enzyme electrode to measure L glutamate. GDH is covalently immobilized in a hydrophilic, permeable, and semirigid gel produced by the copolymerization of polyacrylamide and N acryloxysuccinimide. Experimental conditions necessary to retain GDH in the gel with high efficiency and minimum denaturation are optimized. The abilities of enzymatic cofactors and coenzymes, NADH, NAD, ATP, ADP, GTP, and ZnCl2, to protect the enzyme during immobilization are explored. Under optimum experimental procedures an enzyme-containing gel is produced that is reproducible and long lasting in its functional behavior. The gel responds to the presence of L glutamate with high velocity, the delay being less than 500 ms; high specificity, being 1000-fold more responsive to L-glutamate than D-glutamate, D- or L aspartate, and N-acetylhistidine; and high sensitivity, a concentration of about 3 microM can be measured. PMID- 2883912 TI - A specific radiochemical assay for pyrroline-5-carboxylate dehydrogenase. AB - Previous studies of pyrroline-5-carboxylate dehydrogenase have been conducted using a spectrophotometric method to monitor substrate-dependent NAD(P)H production. For the assay of the mammalian enzyme, the spectrophotometric assay was found to be unacceptable for kinetic studies as the production of NAD(P)H was nonlinear with time and protein concentration. An assay which measures radiolabeled glutamate production by this enzyme in the presence of NAD+ from radiolabeled pyrroline-5-carboxylate has been developed. Separation of substrate from product is achieved by column chromatography using Dowex 50 cation-exchange resin. The product isolated by this procedure was identified as glutamate. This new assay is linear with time and protein concentration and gives reproducible results. The assay is not influenced by competing enzyme activities, such as glutamate dehydrogenase, in a liver homogenate so that quantitative conversion of pyrroline-5-carboxylate to glutamate is observed. PMID- 2883911 TI - Use of fluorescein hydrazide and fluorescein thiosemicarbazide reagents for the fluorometric determination of protein carbonyl groups and for the detection of oxidized protein on polyacrylamide gels. AB - Highly fluorescent thiosemicarbazide and hydrazide prepared by reaction of fluorescein isothiocyanate with hydrazine or adipic acid dihydrazide have been used to monitor the presence of carbonyl groups in oxidatively modified proteins. After oxidation, proteins react with these reagents under anaerobic conditions in the dark to yield fluorescent protein conjugates (presumably thiosemicarbazones or hydrazones) which can be visualized as fluorescent bands following electrophoresis (0-4 degrees C) on lithium dodecyl sulfate-polyacrylamide gels. These reagents do not react with unoxidized proteins. The conjugates formed dissociate readily at room temperature but are fairly stable at pH 6-9, 0 degrees C. Current data suggest that these reagents will be useful in the detection and quantitation of oxidatively modified proteins in biological systems. PMID- 2883913 TI - A procedure for in situ alkylation of cystine residues on glass fiber prior to protein microsequence analysis. AB - A procedure is described which provides high yields of pyridylethylated cysteine during gas-phase sequencing of peptides. The method decreases transfer losses by reducing the number of transfer steps required for reduction, alkylation, prior to sequencing a peptide. Proteins bound to polybrene-coated glass-fiber filters used in a gas-phase sequenator may be reduced, pyridylethylated, and sequenced directly on the filter. Reduction of cystine-containing peptides is performed using the nonnucleophilic reductant, tributylphosphine [U. T. Ruegg and J. Rudinger (1977) in Methods in Enzymology (Hirs, C. H. W., and Timasheff, S. N., Eds.), Vol. 47, pp. 111-116, Academic Press, New York] with concomitant alkylation by 4-vinylpyridine in a buffer soluble in the organic phase. Excess reagents and the buffer are removed by drying the filter and briefly washing with chlorobutane. No N-alkylation is apparent under the conditions described, nor are any amino acid side chains modified. The procedure affords high yields and is particularly useful when subnanomole levels of material must be reduced and alkylated. PMID- 2883914 TI - Distribution of cell types of the islets of Langerhans throughout the pancreas of the Chacma baboon. AB - Biopsies of the pancreas head, tail, and uncinate regions of four baboons were processed for immunocytochemical (ICC) studies by using avidin-biotin-peroxidase label for light microscopy (LM). Toluidine-blue- or methylene-blue-stained 0.5 micron sections of nonosmicated resin-embedded tissue were viewed to locate areas of suitable islets. For ICC investigations, batches 10 microns apart of ten consecutive 1-micron sections throughout ten islets from each of the three regions were immunolabelled for LM. Four slides in each batch were immunolabelled consecutively for insulin, glucagon, somatostatin, and pancreatic polypeptide, the fifth acting as one of the range of controls in each batch. The number of each of the four cell types was counted in at least ten immunolabelled islets from each of the pancreas heads, uncinate portions, and tails. The uncinate region and not the head, as in most mammals, was found to contain significantly higher numbers of pancreatic polypeptide (PP) cells and lower numbers of A (glucagon) and D (somatostatin) cells (P less than .001). The PP cells occurred in clumps and not as described in other mammals as part of the mantle of A, D, and PP cells. PP and A cell numbers were significantly different for each region (P less than .001), being lowest in the head for PP and in the uncinate process for A cells. D cell distribution was similar to that of the A cells whilst a significantly smaller number of B (insulin) cells was found in the tail compared with other regions (P less than .001). PMID- 2883915 TI - Reversal by atropine of tetanic fade induced in cats by antinicotinic and anticholinesterase agents. AB - The tetanic fade induced by intraarterial administration of neostigmine or by subparalyzing doses of d-tubocurarine or hexamethonium was studied in cat anterior tibial muscle preparations. The prior administration of atropine significantly reduced the time for recovery from the tetanic fade induced by the above mentioned drugs. A similar response was seen when atropine was administered prior to neostigmine administration for reversal of paralyzing doses of d tubocurarine. We interpret these results to show that presynaptic muscarinic receptors participate in a negative feedback affecting acetylcholine release at the neuromuscular junction. PMID- 2883917 TI - The administration of bronchodilators into the anesthesia circuit. PMID- 2883916 TI - Neostigmine antagonism of vecuronium paralysis during fentanyl, halothane, isoflurane, and enflurane anesthesia. PMID- 2883918 TI - [The theophylline test in the evaluation of the effect of anesthesia on immunity]. PMID- 2883919 TI - [Metabolism of biogenic amines in the acute period of severe cranio-cerebral injuries while using pharmacologic protection of the brain from hypoxia as part of complex treatment]. PMID- 2883920 TI - Different effects of beta-1-adrenergic blocking agents with ISA or without ISA on peripheral blood flow. AB - Until recently beta-adrenergic blocking agents were considered contraindicated in peripheral arterial occlusive disease (PAOD). However, in recent years several studies have failed to show negative effects on peripheral blood flow. It was the aim of this study to compare the effects of celiprolol, a beta-1-adrenergic blocking agent with intrinsic sympathomimetic activity (ISA), and of metoprolol, a beta-1-adrenergic blocking agent without ISA, on peripheral blood flow of patients with and without PAOD. In an acute trial 24 patients (group I: 12 patients with PAOD stage I and II; group II: 12 patients without PAOD received a single dose of 200 mg celiprolol or 200 mg metoprolol in a double-blind crossover design. Celiprolol induced no significant changes in calf and skin blood flow at rest or during reactive hyperemia. Basal vascular resistance (BVR) and minimal vascular resistance (MVR) were not affected. Metoprolol, however, significantly reduced muscle blood flow and increased BVR in both groups. Subsequently the patients were treated in a randomized double-blind design with a daily dose of 200 mg celiprolol or metoprolol for three weeks. In long-term treatment skin and muscle blood flow at rest and during reactive hyperemia, BVR, and MVR were not affected by celiprolol. Metoprolol significantly lowered calf blood flow at rest in patients with PAOD; other parameters remained unchanged. In patients without PAOD, metoprolol caused a significant decrease of calf blood flow at rest and an increase of BVR. Calf blood flow during reactive hyperemia, as well as skin blood flow at rest and during reactive hyperemia, showed no significant changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883921 TI - Mosquito hypersensitivity. PMID- 2883923 TI - Carotid body tumor and hyperparathyroidism. A case report and review of the literature. AB - Carotid body tumor is an uncommon tumor of the head and neck. The coexistence of this entity with primary hyperparathyroidism is even more unusual, with only four cases having been previously recorded. This report describes a patient with a left inferior parathyroid adenoma and a right carotid body tumor. A common neuroectodermal origin is proposed as an explanation for the simultaneous occurrence of these tumors. The fact that this may represent yet another variable expression of the multiple endocrine neoplasia syndromes emphasizes the importance of careful endocrine screening in patients with carotid body tumors. PMID- 2883924 TI - [Epididymo-testicular disjunction. Presentation of 23 cases and review of the literature]. AB - Twenty three cases of alterations of the epididymis-testicular union found in 1,000 children with cryptorchism are discussed. Anatomical and pathological findings are described and world literature on the subject is reviewed, finding very scanty references to this problem in spite of the fact that expected incidence of epididymis testicular non-junction is between 1 and 2% of the patients with cryptorchism. PMID- 2883922 TI - Modulation of rabbit airway smooth muscle responsiveness by respiratory epithelium. Involvement of an inhibitory metabolite of arachidonic acid. AB - The integrity of the respiratory epithelium may be important in development of bronchial hyperreactivity; however, the mechanisms involved remain unknown. This study was undertaken to determine if epithelium of rabbit intrapulmonary bronchi is capable of modulating the responsiveness of airway smooth muscle to a pharmacologic stimulus, and whether epithelial-derived prostaglandins play a role in this modulatory function. Mechanical removal of the epithelium from bronchial segments, or incubation of intact bronchi with indomethacin (an inhibitor of prostaglandin synthesis) increased the sensitivity of bronchial smooth muscle to bethanechol. Cyclooxygenase was localized within mucosal epithelial cells of intact airways by avidin-biotin immunoperoxidase staining using a monoclonal antibody to the enzyme. Removal of the epithelium significantly reduced the levels of PGE2 and 6-keto-PGF1 alpha accumulated in the media surrounding bronchial explants. In epithelium-intact bronchi precontracted with bethanechol, arachidonic acid evoked an indomethacin-sensitive relaxation response comparable to relaxation induced by exogenous addition of PGE2. Although PGE2 evoked similar responses in epithelium-denuded bronchi, arachidonic acid-induced relaxation responses were negligible. The results suggest epithelial cells of rabbit bronchi modulate the responsiveness to pharmacologic stimuli by production and release of an inhibitory cyclooxygenase metabolite of arachidonic acid. PMID- 2883925 TI - The use of deoxyribonucleic acid probes in the evaluation of hemophilia. AB - The use of deoxyribonucleic acid (DNA) probes is an important addition to existing laboratory methods for detection of carriers of hemophilia A and B. Both intragenic probes and probes directed at DNA restriction fragment length polymorphisms linked to the disease locus are now available. This technology will aid in genetic counseling of affected families and will impact upon clinical laboratory science in the near future. PMID- 2883926 TI - [Towards a genealogy of chromosome Y]. AB - Taq I restriction polymorphisms of the 49 f genomic probe are used to establish a possible filiation of the Y chromosome in human populations. Relationships between alleles at the five polymorphic loci revealed by the probe allow the description of 17 haplotypes. Simulations are used to construct a plausible genealogy of these various haplotypes, on the basis of a limited set of basic hypotheses concerning polymorphic alleles evolution. PMID- 2883927 TI - Linkage of adrenoleukodystrophy to a polymorphic DNA probe. AB - Linkage studies between X-linked adrenoleukodystrophy and a cloned deoxyribonucleic acid fragment (St14), which detects polymorphisms in the distal end of the long arm of the X chromosome (Xq27-28), have shown no recombination in six families. The lod score for these data (and another kindred reported earlier is 13.766 at recombination fraction (theta) = 0.0. These data permit assignment of adrenoleukodystrophy carrier status in family members at risk, supplementing the chemical measurement of very-long-chain fatty acids. PMID- 2883928 TI - Clinical utility of biochemical assays in psychiatry. AB - Biological abnormalities are found almost consistently in schizophrenia and affective disease. While most remain as research leads, some are sufficiently well studied that they are now or may soon enter in routine medical practice. The dexamethasone test (DST) has been investigated thoroughly enough so it should pass into practice. PMID- 2883929 TI - Cotransmission. AB - Cotransmission, defined here as the control of a single target cell by two or more substances released from one neuron in response to the same neuronal event, does occur in experimental situations. It has not been shown to occur in the normal operation of an animal, but the likelihood that it does is great. There are many examples of potential transmitters coexisting in one neuron, suggesting that cotransmission might be widespread in the peripheral nervous system. But many transmissions still seem to be mediated by a single transmitter. In such cases, coreleased substances might act on other targets or modulate the receptors for the main transmitter. But the possibility also exists that some colocalized "transmitters" have no function in transmission. It is increasingly difficult to retain a simple classification of neuronal types based on transmitter substances. However, there are indications that some combinations of colocalized substances are "preferred" and that certain combinations typify the innervation of a particular target tissue. PMID- 2883930 TI - Thiols in oxidative phosphorylation: thiols in the F0 of ATP synthase essential for ATPase activity. AB - It was shown previously that the ATP synthase complex of bovine heart mitochondria contains an essential set of thiols or dithiols in its membrane sector (F0), whose modification by various reagents results in uncoupling [Yagi, T., and Hatefi, Y. (1984) Biochemistry 23, 2449-2455]. The sensitivity to modifiers was increased by membrane energization, and the uncoupling was reversed by membrane-permeable thiol compounds when modifiers other than alkylating agents were used to uncouple. The present paper demonstrates that there exists in the F0 of bovine ATP synthase another set of essential thiols, whose modification results in reversible inhibition of ATPase activity. These thiols are most susceptible to modification by mercurials (p-chloromercuribenzoate greater than p chloromercuribenzene sulfonate) and do not appear to be modified by N ethylmaleimide. The reversible modification of these thiols by mercurials protects the ATP synthase against irreversible inhibition in F0 by N,N dicyclohexylcarbodiimide. The possible location of these two sets of thiols in the F0 of bovine ATP synthase is discussed. PMID- 2883931 TI - Acetoacetyl-CoA thiolase of Bradyrhizobium japonicum bacteroids: purification and properties. AB - Acetoacetyl-CoA thiolase of Bradyrhizobium japonicum bacteroids has been purified greater than 130-fold. The enzyme has a molecular weight of 180,000 +/- 15,000 and consists of four identical subunits of 44,000 +/- 2,000. The enzyme was specific for acetoacetyl-CoA; ketodecanoyl-CoA did not serve as a substrate. Catalysis proceeds via a ping-pong mechanism. Iodoacetamide effectively inhibited the enzyme but acetoacetyl-CoA provided considerable protection against this compound. Magnesium was found to inhibit both the thiolysis reaction and the condensation reaction. Acetoacetyl-CoA thiolysis activity was not affected by potassium, ammonium, or several organic acids but was found to be inhibited by NADH. The inhibition by NADH may have an effect during the decline of the symbiosis. PMID- 2883932 TI - Binding of Mg2+ to the beta subunit or F1 of H+-ATPase from Escherichia coli. AB - The bindings of Mg2+ to the F1 portion of Escherichia coli H+-ATPase and its isolated alpha and beta subunits were studied with 8-anilinonaphthalene-1 sulfonate (ANS). The fluorescence of ANS increased upon addition of F1 or its alpha subunit or beta subunit, as reported previously (M. Hirano, K. Takeda, H. Kanazawa, and M. Futai (1984) Biochemistry 23, 1652-1656). The fluorescence of ANS bound to F1 or its beta subunit increased significantly with further addition of Mg2+, whereas that of the alpha subunit increased only slightly. Ca2+ and Mn2+ had similar effects on the fluorescence of ANS with F1 and its beta subunit. The Mg2+-induced fluorescence enhancement (delta F) was high at an alkaline pH and was lowered by addition of ethylenediaminetetraacetic acid. Dicyclohexylcarbodiimide and azide had no effect on the delta F. Binding analysis showed that the concentration dependence of Mg2+ on the fluorescence enhancement of the beta subunit is similar to that of F1. These results suggest that both the beta subunit and F1 have binding sites for Mg2+ and that the delta F observed with F1 may be due to the binding of Mg2+ to the beta subunit. PMID- 2883933 TI - Localization of two L-glutamate dehydrogenases in the coral Acropora latistella. AB - The coral Acropora latistella has been shown to contain two distinct L-glutamate dehydrogenases. An NADPH-specific GDH, closely resembling the enzyme from other coelenterates, is located in the cytosol; a distinct NADH-specific GDH is localized within the mitochondria. This is in contrast to earlier reports, where the NADPH-specific enzyme was thought to be the only GDH present and was assumed to be mitochondrial. Preliminary kinetic and stability data are presented for the two GDHs. PMID- 2883934 TI - Post-translational modifications of chloroperoxidase from Caldariomyces fumago. AB - The secreted form of the halogenating glycoenzyme, chloroperoxidase, is processed from a precursor containing a 21-residue-long, moderately hydrophobic signal sequence, at an atypical Gln-Glu peptide bond. Following cleavage, the N-terminal glutamic acid readily cyclizes into pyroglutamic acid. Chloroperoxidase contains two high-mannose N-glycosylation sites, identified as Asn12 and Asn213. Other modifications include deamidation of residues Asn13, Asn198, and Gln183 into the corresponding acids. Finally, structural arguments suggest that Cys87 may be the axial heme ligand in the active site of chloroperoxidase. PMID- 2883935 TI - Structure of a methanofuran derivative found in cell extracts of Methanosarcina barkeri. AB - Cell extracts prepared from cells of Methanosarcina barkeri grown on hydrogen and carbon dioxide, acetate, or methanol contain a coenzyme structurally related to methanofuran. This modified coenzyme was highly purified and its structure assigned as 4-[N-(gamma-L-glutamyl-gamma-L-glutamyl-gamma-L-glutamyl-gamma-L glutamy l)-p- (beta-amino-ethyl)phenoxymethyl]-2-(aminomethyl)furan. The key structural evidence was obtained by high-resolution fast atom bombardment-mass spectrometry and 1H NMR spectroscopy. Quantitative analysis of the hydrolytic fragments of the coenzyme supported the assigned structure. We propose that this coenzyme be called methanofuran-b. PMID- 2883936 TI - [Initial basic and clinical evaluation of a solid-phase immunoradiometric assay for sialyl SSEA-1 antigen: 1. Evaluation of assay conditions and normal values]. AB - We describe a solid-phase immunoradiometric sandwich assay method for a new tumor marker, sialyl SSEA-1 (sialyl LeX-i), using RIA kits (prepared by Otsuka Assay Laboratories). The assay required only duplicate 20-microliter samples, and the concentration of sialyl SSEA-1 antigen in serum was determined with reference to a standard curve ranging from 0 to 224 arbitrary unit/ml. The intra- and inter assay reproducibilities and analytical recovery of antigen were excellent. The cut-off value (38 unit/ml) was obtained as mean + 2SD, which was calculated from the antigen concentration in sera from 1,105 healthy individuals. Also described are the alterations of normal values by age, sex, and Lewis blood group status. PMID- 2883938 TI - Postgranulomatous anetoderma associated with Takayasu's arteritis in a child. AB - Takayasu's arteritis (TA) is a rare chronic inflammatory arteriopathy affecting mainly the aorta and its branches. Many skin manifestations have been reported in association with this disease. Pyoderma gangrenosum and subcutaneous inflammatory lesions of the leg are the most frequent. We studied a boy with TA in whom a papular rash of the trunk preceded the onset of vascular symptoms by many years. Histologically, the lesions were superficial and consisted of middermal noncaseating tuberculoid granulomas, which progressed to atrophy and anetoderma because of elastic network disruption. Granulomas were also found in synovial tissue but not in a temporal artery biopsy specimen, which showed only intimal hyperplasia. Our observations suggest that vascular and skin lesions with elastic tissue may both result from a common granulomatous hypersensitivity process. PMID- 2883937 TI - [Initial basic and clinical evaluation of a solid-phase immunoradiometric assay for sialyl SSEA-1 antigen: 2. Evaluation of clinical significance]. AB - The clinical significance of serum sialyl SSEA-1 antigen was evaluated using the sera of 1261 patients with malignant tumors and 717 patients with non-malignant diseases measured with Otsuka Assay Laboratories' RIA Kits. The results indicate that the antigen was frequently elevated in the sera from the patients with various adenocarcinomas, including lung (45%), pancreas (64%) and ovary (57%). The false positive incidence of antigens in the sera from the patients with non malignant disorders was as low as 4.9%. No correlation was observed with other tumor markers examined in this study, and the diagnostic efficiency increased significantly by the combined determination of sialyl SSEA-1 antigen level with other markers. The serial determination of the serum sialyl SSEA-1 antigen level has a clinical utility also in monitoring the patients with adenocarcinoma receiving surgical operation and/or chemotherapy as indicated by the results of the longitudinal observation of the patients. PMID- 2883939 TI - Long-term treatment of rheumatoid arthritis with sulphasalazine, gold, or penicillamine: a comparison using life-table methods. AB - Life-table analysis was applied to the records of 317 patients with rheumatoid arthritis (RA) treated with sulphasalazine (SAS), 201 treated with sodium aurothiomalate (gold), and 163 with penicillamine. They comprised all those treated in our department with these drugs between January 1973 and July 1984. Risks of treatment termination for all reasons were similar for each drug at five years (gold 92%, penicillamine 83%, SAS 81%). The risk of treatment termination due to inefficacy was less for gold (29.5%) than for penicillamine (38.1%) or sulphasalazine (41.2%). Adverse effects, however, led to withdrawal of gold in 57%, penicillamine in 41.2%, and SAS in 37%; the most effective drugs appeared most toxic. Serious adverse effects were much more common in association with gold (17.4%) and penicillamine (12.3%) than with SAS (1.6%). Sulphasalazine appears as well tolerated over long periods in RA as gold or penicillamine and is associated with fewer serious adverse effects; of these drugs, it might therefore be considered the agent of first choice. PMID- 2883941 TI - Labetalol protects against the potentiation by propranolol of the bronchospasm to norepinephrine in guinea-pigs. AB - The increase in airway obstruction observed in asthmatics after treatment with beta-adrenergic blockers may be attributed to an unopposed alpha-adrenergic activity. Labetalol is an antihypertensive agent with beta-adrenoreceptor and alpha-adrenoreceptor blocking properties. Labetalol does not cause a bronchospasm in human asthmatics. Norepinephrine (0.025-0.1 mg/kg, i.v.) caused a bronchospasm in guinea-pigs after the blockade of beta-adrenoreceptors with propranolol (0.1-1 mg/kg, i.v.), but not after beta-blockade with labetalol (0.1-10 mg/kg, i.v.). Labetalol significantly protected against the bronchospasm induced by norepinephrine in the presence of propranolol. The bronchospasm induced by norepinephrine was inhibited by alpha-adrenergic blockade with phentolamine (0.03 3 mg/kg, i.v.), but not by blockade of receptors for histamine, acetylcholine or sulfidopeptide leukotrienes or by inhibition of cyclooxygenase activity. The lack of a bronchospasm after stimulation of alpha 2-receptors with B-HT 920 suggests that the bronchospasm to norepinephrine was due to the activation of alpha adrenoreceptors on airway smooth muscle. The more desirable pulmonary profile of labetalol compared with other beta-blockers may be due, in part, to the interaction of labetalol with both beta- and alpha-adrenoreceptors. PMID- 2883940 TI - Sulphasalazine and regression of rheumatoid nodules. AB - The regression of small rheumatoid nodules was noted in four patients after starting sulphasalazine therapy. This coincided with an improvement in synovitis and also falls in erythrocyte sedimentation rate (ESR) and C reactive protein (CRP). The relation between the nodule regression and the sulphasalazine therapy is discussed. PMID- 2883942 TI - Involvement of central type benzodiazepine and GABAA receptor in the protective effect of benzodiazepines in stress-induced gastric ulcers in rats. AB - Various benzodiazepines (BZs) were studied for ulcer protective effect in immobilization stress-induced gastric ulcers in rats. Central type BZ receptor agonists such as clonazepam, chlorodiazepoxide and diazepam shared marked antiulcer effect. The ulcer protective action of these agents was reversed by pretreatment with Ro 15-1788, a central BZ receptor antagonist. However, peripheral BZ receptor binding agent Ro 5-4864 and BZ-micromolar binding agent phenytoin, failed to show any antiulcer effect. Pretreatment with bicuculline also reversed the ulcer protective action of central type BZ receptor agonists. A bicuculline sensitive potentiation was observed in the ulcer protective effect of central BZ receptor agonist, when a subeffective dose was combined with muscimol, a specific GABAA agonist. But no such potentiation was seen with baclofen, a GABAB agonist. These data imply an interaction of central type BZ receptor with GABAA subtype receptor in the ulcer protective effect of benzodiazepines in rats. PMID- 2883943 TI - Effects of urapidil on neurotransmitter release in CNS tissue in vitro. AB - The effects of the antihypertensive drug urapidil on the electrically evoked release of [3H]-noradrenaline (NA) in rabbit cortex slices, of [3H]-acetylcholine (ACh) and [3H]-5-hydroxytryptamine (5-HT) in rabbit hippocampus slices, and of [3H]-ACh and [3H]-dopamine (DA) in rabbit caudate nucleus slices were investigated. Urapidil significantly increased basal tritium outflow in slices preincubated with [3H]-NA and showed weak alpha 2-adrenoceptor antagonism on the evoked NA-release. The pA2-value of urapidil against the inhibitory effect of the alpha 2-agonist clonidine was about 6.3. In contrast to phentolamine, urapidil exhibited no partial agonistic properties at alpha 2-adrenoceptors in this model when stimulation was performed at low frequency and in the absence of cocaine. Neither the evoked ACh- nor 5-HT-release in hippocampal slices were affected by urapidil in concentrations up to 10 microM, but basal tritium outflow was significantly enhanced from slices preincubated with [3H]-5-HT. In caudate nucleus slices urapidil (greater than 1 microM) significantly facilitated both the evoked ACh- and DA-release, effects which were enhanced by the DA-reuptake inhibitor nomifensine. The effects of the D2-dopamine receptor selective agonist LY 171555 and the D2-receptor antagonist domperidone on the evoked DA-release were reduced by 1 microM urapidil. In addition, urapidil (10 microM) increased basal tritium outflow from slices preincubated with [3H]-DA. It is concluded that the antihypertensive effect of urapidil is not mediated by presynaptic actions affecting NA- or 5-HT-release within the CNS. Whether an increased dopaminergic or cholinergic transmission following the observed enhancement of DA- or ACh release (due to a weak D2-receptor antagonism) is involved, remains to be further elucidated. PMID- 2883944 TI - Acetaldehyde and cardiac arrhythmias. AB - Administration of acetaldehyde (i.v.) into cats anesthetized with halothane elicits severe cardiac ventricular arrhythmias which begin in about 10-13 sec with bolus doses of 5-10 mg/kg, and last about 2 min. Systemic blood pressure and heart rate rise concurrently with the arrhythmias. The cardiac effects are attributed to the release of endogenous catecholamines from cardiac tissue because they are prevented by beta-adrenergic blockade and are not dependent on adrenomedullary and splenic stores of catecholamines, since acute surgical removal of these tissues does not prevent the arrhythmias and other cardiovascular changes. This indirect arrhythmogenic action of acetaldehyde has not been previously reported, probably because other investigators have used anesthetics like pentobarbital which exert an antiarrhythmic effect that masks acetaldehyde's arrhythmogenic potential. The use of halothane to sensitize the heart to catecholamines greatly enhanced the arrhythmogenic effect of acetaldehyde. The question is raised whether the concomitant industrial or medical exposure of human subjects to large amounts of exogenous or endogenous acetaldehyde and certain hydrocarbons could provide the substrate for the expression of this arrhythmogenic effect of acetaldehyde. PMID- 2883945 TI - Characterization of the alpha-adrenoceptors mediating positive inotropy of rat left atria by use of selective agonists and antagonists. AB - Positive inotropic responses to selective alpha-adrenoceptor agonists of isolated paced left atria and chronotropic responses of isolated spontaneously beating right atria of rats were examined. After establishing a cumulative concentration response curve to isoprenaline, and washout, a concentration-response curve for phenylephrine, methoxamine, cirazoline, amidephrine or UK 14,304 was constructed in the presence of beta-adrenoceptor blockade by propranolol. The 4 alpha 1 selective agonists produced positive inotropic responses, the order of maximum effectiveness being methoxamine greater than phenylephrine greater than cirazoline greater than amidephrine. In terms of EC50 values, methoxamine was the least potent, the other 3 agonists having approximately equivalent potencies. The alpha 2-selective agonist UK 14,304 had no inotropic activity. Weak positive chronotropic activity occurred with phenylephrine, methoxamine and amidephrine; cirazoline exerted only negative chronotropy and UK 14,304 was without effect. Phenylephrine was examined in the absence or presence of prazosin (3 nM) or propranolol (1 microM). Propranolol failed to affect the concentration-response curve for left atrial tension, but prazosin displaced the curve to the right. This indicates that the inotropic responses obtained in the absence of antagonists were mediated solely via alpha-adrenoceptors. After displacement by prazosin there was a further shift by propranolol, suggesting the presence of a beta-adrenoceptor-mediated component at higher concentrations of phenylephrine. The right atrial rate responses to phenylephrine were unaffected by prazosin, but abolished by propranolol; beta-adrenoceptors only are therefore involved in this response. The pA2 values for antagonism of methoxamine-induced increases in left atrial tension by the alpha 1- and alpha 2-selective antagonists prazosin (9.05 +/- 0.06) and idazoxan (6.37 +/- 0.05), respectively, were consistent with the responses being mediated via alpha-adrenoceptors of the alpha 1-subtype. The pA2 value for prazosin was similar to that obtained for antagonism of methoxamine induced contractions of rat aortic spirals (8.83 +/- 0.13). PMID- 2883946 TI - Does the beta 1-adrenoceptor blocking agent celiprolol have alpha 2-adrenoceptor blocking properties? AB - The beta 1-adrenoceptor blocking agent celiprolol was tested for alpha 2 adrenoceptor blocking properties in different pharmacological models. In radioligand binding studies celiprolol shows a tenfold higher affinity to alpha 2 in comparison to alpha 1-adrenoceptors; however, the affinity of celiprolol to alpha-adrenoceptors is at least 100 times lower than that to beta-adrenoceptors. Celiprolol enhances the inhibitory effect of the alpha 2-adrenoceptor agonist clonidine in the electrically stimulated rat vas deferens in vitro; this celiprolol effect is abolished, but not reversed by propranolol. In pithed rats celiprolol inhibits the tachycardia induced by spinal electrical stimulation; the inhibitory effect of clonidine on the same parameter is augmented by celiprolol, but reversed by rauwolscine. Also in pithed rats celiprolol does not affect the pressor effect of the alpha 2-adrenoceptor agonist B-HT 920. From these results it is concluded that celiprolol does not possess any relevant alpha 2 adrenoceptor blocking properties which could explain the broncho- and vasodilating actions of that substance. PMID- 2883947 TI - The mode of action of ifenprodil tartrate in isolated canine cerebral and femoral arteries. AB - Tension of isolated rings of cerebral and femoral arteries was measured isometrically and Ca2+ movement in these arteries was measured by 45Ca flux to study the mode of action of ifenprodil tartrate (IFT). IFT (10(-7)-10(-4) M) induced relaxation in basilar and femoral arteries contracted by K+ (50 mM). During normoxia (O2 aeration) it induced contraction in arteries contracted by prostaglandin (PG)F2 alpha (10(-5) M), but induced relaxation during hypoxia (N2 aeration). In K+-induced contraction the relaxed tension induced by IFT was reversed by addition of Ca2+ in a dose-dependent manner. The IFT induced relaxation of femoral arteries contracted by K+ was attenuated in Ca2+-free solution containing 0.1 mM EGTA, and the effect of IFT on basilar and femoral arteries contracted by PGF2 alpha was reversed. IFT inhibited K+-induced Ca2+ uptake in cerebral and femoral arteries. IFT enhanced PGF2 alpha-induced Ca2+ uptake in cerebral arteries under normoxia, but inhibited it under hypoxia. The results suggest that the action of IFT may be due to alteration of Ca2+ utilization by vascular cells through blockade of potential-sensitive channels, and this action may reflect regional differences between arteries. PMID- 2883948 TI - Effects of decarboxylase inhibitors on muricidal suppression by L-dopa in thiamine deficient rats. AB - Male Wistar rats maintained on a thiamine deficient diet showed mouse-killing behavior (muricide). On the 30th day of experimental feeding, the incidence of the muricide was 70%. Intraperitoneal (i.p.) injection of 3-(3,4-dihydroxyphenyl) l-alanine (l-dopa) suppressed the muricide in a dose-dependent manner. This suppressive effect was potentiated with carbidopa, but was quite reduced by pretreatment with alpha-monofluoromethyldopa or FLA-63. These results indicated that the effect of l-dopa was dependent on its decarboxylation, and its conversion to noradrenaline (NA) essential for muricidal suppression in the brain. The NA precursors, l-dopa, l-threo-dops or maprotiline and Y-8894, which can increase the availability of synaptic catecholamines (CA), also showed muricidal suppression. CA depletors (alpha-methyl-p-tyrosine, FLA-63 and alpha monofluoromethyl-p-tyrosine) did not significantly increase the incidence of muricide induced by thiamine deficiency nor decrease the number of killer-rats. These findings suggest that brain CA may not participate in the mediation of muricide induced by thiamine deficiency in this experiment, but such muricide can be pharmacologically characterized by the effects which are brought about by catecholaminergic agents. PMID- 2883949 TI - Treatment of gastroesophageal reflux-induced asthma: steroids, beta 2-stimulants, and H2-blockers. PMID- 2883950 TI - Osmoregulation in Escherichia coli by accumulation of organic osmolytes: betaines, glutamic acid, and trehalose. AB - It has been shown previously that externally added glycine betaine is accumulated in Escherichia coli in response to the external osmotic strength. Here we have shown, by using nuclear magnetic resonance spectroscopy and radiochemical methods, that E. coli growing in a glucose-mineral medium of elevated osmotic strength generated with NaCl, had the same capacity to accumulate proline betaine and glycine betaine. Its capacity to accumulate gamma-butyrobetaine was, however, 40 to 50% lower. Accordingly, externally added proline betaine and glycine betaine stimulated aerobic growth of osmotically stressed cells equally well, and they were more osmoprotective than gamma-butyrobetaine. In cells grown at an osmotic strength of 0.64, 1.01, or 1.47 osmolal, respectively, the molal cytoplasmic concentration of the two former betaines corresponded to 29, 38, or 58% of the external osmotic strength. Nuclear magnetic resonance spectroscopy revealed that trehalose and glutamic acid were the only species of organic osmolytes accumulated in significant amounts in cells grown under osmotic stress in glucose-mineral medium without betaines. Their combined molal concentration in the cytoplasm of cells grown at 1.01 osmolal corresponded to 27% of the external osmotic strength. PMID- 2883952 TI - [Effects of gonadoliberin administered nasally in cryptorchidism in aged 1 to 6]. AB - 93 cryptorchid boys aged 1 to 6 years were treated with nasal spray of LHRH according with two different protocols: 0.4 mg thrice daily during 28 consecutive days in 39 (32 uni and 7 bilaterally cryptorchid) and 0.4 mg twice daily on alternate days three days per week for 1 month in 32 and 3 months in 22 (34 uni and 20 bilaterally cryptorchid). The results did not vary according to age or to the protocol and duration of treatment. Complete testicular descent was obtained for only 10% of unilaterally undescended testes, and reached 29% in bilaterally undescended testes. These results do not relate to the more or less high position of the testis nor to hypothetical changes in plasma gonadotropins or testosterone. The treatment had very minor side-effects. For this reason, in spite of its very limited results, it may be used either as an attempt before surgery at 4-6 years or as a means to distinguish retractile from undescended testes. PMID- 2883951 TI - A proton-translocating adenosine triphosphatase is associated with the peroxisomal membrane of yeasts. AB - The association of an ATPase with the yeast peroxisomal membrane was established by both biochemical and cytochemical procedures. Peroxisomes were purified from protoplast homogenates of the methanol-grown yeast Hansenula polymorpha by differential and sucrose gradient centrifugation. Biochemical analysis revealed that ATPase activity was associated with the peroxisomal peak fractions which were identified on the basis of alcohol oxidase and catalase activity. The properties of this ATPase closely resembled those of the mitochondrial ATPase of this yeast. The enzyme was Mg2+-dependent, had a pH optimum of approximately 8.5 and was sensitive to N,N'-dicyclohexylcarbodiimide (DCCD), oligomycin and azide, but not to vanadate. A major difference was the apparent Km for ATP which was 4-6 mM for the peroxisomal ATPase compared to 0.6-0.9 mM for the mitochondrial enzyme. Cytochemical experiments indicated that the peroxisomal ATPase was associated with the membranes surrounding these organelles. After incubations with CeCl3 and ATP specific reaction products were localized on the peroxisomal membrane, both when unfixed isolated peroxisomes or formaldehyde-fixed protoplasts were used. This staining was strictly ATP-dependent; in controls performed in the absence of substrate, in the presence of glycerol 2-phosphate instead of ATP, or in the presence of DCCD, staining was invariably absent. Similar staining patterns were observed in subcellular fractions and protoplasts of Candida utilis and Trichosporon cutaneum X4, grown in the presence of ethanol/ethylamine or ethylamine, respectively. PMID- 2883954 TI - Age and histopathologic heterogeneity in Alzheimer's disease. Evidence for subtypes. AB - In support of heterogeneity in Alzheimer's disease (AD), the existence of clinical and biologic subtypes has been claimed. We have investigated this claim by a statistical analysis of the relationships between the number of neurons in nucleus locus ceruleus (nLC), cortical levels of neurotransmitters, number of cortical plaques and tangles, and age. We separated AD patients into two groups: AD-1, with a less severe loss of nLC neurons; and AD-2, with a greater loss. The AD-2 cases were associated with less choline acetyltransferase activity, smaller concentrations of somatostatin and norepinephrine, and more plaques and tangles in the cerebral cortex. Although the mean age at death was less and the duration of dementia was greater in AD-2 patients than in AD-1 patients, the differences in these age-related variables were not significant. Further evidence of heterogeneity came from discriminant function analyses based on nLC neuronal counts and age at death. These findings, suggesting two subtypes of AD, suggest heterogeneity. PMID- 2883953 TI - [Acquired deficiencies in antithrombin III and C protein during treatment with L asparaginase]. AB - Fourteen children treated by L-Asparaginase for acute lymphoblastic leukemia had sequential coagulation studies performed including cephalin-kaolin time, Quick time, fibrinogen, factors II, VII + X and V, as well as antithrombin III and protein C, the major coagulation inhibitors. A severe antithrombin III and protein C deficiency was observed during therapy, with a coexisting hypocoagulability. This equilibrium partially explains the lack of thrombo embolic phenomena in these children, despite the risk factors present. Although no substitutive therapy was instituted in these cases, their use in high-risk cases is discussed. PMID- 2883956 TI - [H2-antihistaminics. 34. 1,3,4-Oxadiazol-2,5-diamines with H2-antagonistic activity]. PMID- 2883955 TI - [H2-antihistaminics. 33. Synthesis and H2-antagonistic activity of heteroaromatic (thio)carboxamides and triazole(thi)one-derivatives of piperidinomethylphenoxypropylamine]. PMID- 2883957 TI - [Histamine analogs. 28. 2-(Aryloxyalkyl)- and 3(aminoalkyl)-histamines]. PMID- 2883959 TI - [Structure-activity relationships in histamine H2 receptor antagonists: construction of a binding site model]. PMID- 2883958 TI - Analyses of drugs by polarographic methods, XXVIII: Electroanalysis of quazepam [7-chloro-5-(2-fluorophenyl)-1.3-dihydro-1-(2.2.2-trifluoroethyl)- 2H-1.4 benzodiazepine-2-thione]. PMID- 2883960 TI - Biological markers characterizing the development of preneoplastic and neoplastic lesions in rodent liver. AB - The identification of biological "markers" indicating distinctively different functions between preneoplastic and neoplastic as compared with normal cells has been a subject of intensive investigation, especially as additional technology becomes available. Although no distinct single biochemical marker is ubiquitous to the process of neoplasia or even to a single histogenetic type of neoplasm, a variety of histogenetic types of neoplasms in the human and experimental animals exhibit an extreme degree of marker or phenotypic heterogeneity. Particularly well studied are markers which occurred during the process of hepatocarcinogenesis in the rodent as well as in its final product, the hepatoma. Although phenotypic heterogeneity is characteristic of hepatocellular carcinomas in both the rat and mouse, some degree of predominant marker pattern(s) has become apparent. In multistage hepatocarcinogenesis in the rat a frequent but not completely ubiquitous marker is the enzyme gamma-glutamyltranspeptidase. In the mouse, although such markers have not been as extensively studied as in the rat, glucose 6-phosphatase is a predominant but not exclusive histochemical marker. Many preneoplastic lesions occurring during the stage of promotion exhibit reduced levels of enzymes of oxidative xenobiotic metabolism, but this pattern is not ubiquitous. Studies on the transcription of specific genes in mouse liver as well as preneoplastic and neoplastic lesions in this tissue further demonstrate the phenotypic heterogeneity characteristic of differentiated hepatocellular carcinomas. In general, current evidence supports the two theses that no single biologic marker or set of markers is uniquely characteristic of the preneoplastical and/or neoplastic phenotype and marker or phenotypic heterogeneity is by far the rule rather than the exception in hepatocarcinogenesis in the rodent and quite possibly in all histogenetic types of neoplasms in mammals. PMID- 2883961 TI - [Cardiac aspects of Takayasu arteritis. Report of 2 cases]. PMID- 2883962 TI - Human T-lymphotropic virus type I antibodies in the serum of patients with tropical spastic paraparesis in the Seychelles. AB - Tropical spastic paraparesis (TSP), a chronic myelopathy of unknown etiology, was studied in the Seychelles. Human T-lymphotropic virus type I (HTLV-I) and human immunodeficiency virus antibodies were determined using an enzyme-linked immunosorbent assay and confirmed with an indirect fluorescent antibody test in serum samples of 20 patients with TSP and 16 controls. Test results indicated that 17 patients (85%) and two controls (transverse myelopathy and clinically probable multiple sclerosis) were positive for HTLV-I. Serum samples of nine healthy controls and five with other neurologic diseases were negative for HTLV I. No serum samples were positive for human immunodeficiency virus. Estimated relative risk for TSP in those subjects whose serum is positive for HTLV-I antibodies is 40. This result is highly statistically significant. Although primarily associated with adult T-cell leukemia and non-Hodgkin's lymphoma, HTLV I could also be an etiologic agent of TSP. PMID- 2883963 TI - Clinical electrophysiologic studies of HTLV-I-associated myelopathy. AB - Six patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) were studied by electrophysiologic methods. Upper-limb short latency somatosensory evoked potentials showed slight delay of the N9-N20 interpeak latency in one of 12 limbs, while the lower-limb short-latency somatosensory evoked potentials showed prolonged N20-P40 interpeak latency in eight of 12 limbs. Frequent polyphasic potentials and occasional giant spikes were observed in the distal extremities. F-wave conduction velocity was delayed in some patients. Results of the other nerve conduction studies were unremarkable. Our data provide a valuable extension of the clinical examination of HAM and offer encouragement for a more extensive electrophysiologic study of this entity, especially in the spinal cord. PMID- 2883964 TI - Retrovirus-associated myelopathies. AB - Human T-lymphotropic virus type I (HTLV-I), the causative agent of adult T-cell leukemia and non-Hodgkin's lymphoma (ATLL)--or a cross-reacting retrovirus--has been associated with tropical spastic paraparesis in Martinique, Jamaica, Colombia, Trinidad and Tobago, the Seychelles, and probably also in Zaire. The Caribbean basin and sub-Saharan Africa are endemic for ATLL. A similar etiology has been invoked in a chronic spastic myelopathy occurring in areas of high ATLL endemicity in Japan. An HTLV-I viral antigen has been demonstrated in cerebrospinal fluid lymphocytes of a Japanese patient with myelopathy. Human T lymphotropic virus type I antibodies have occurred in patients in Florida and Japan (areas of HTLV-I endemicity) who were diagnosed as having clinically definite multiple sclerosis (MS), but not in patients with MS in other parts of the world. Human T-lymphotropic virus type I, like some lentiviruses--visna and human immunodeficiency virus, in particular--may be both lymphotropic and neurotropic. Tropical spastic paraparesis, the Japanese myelopathy, and, perhaps, an MS-like neurologic syndrome, may represent clinical variants of the same disease, a retroviral myelopathy. PMID- 2883965 TI - Effect of division of genitofemoral nerve on testicular descent in the rat. AB - The gubernaculum, which has an important role to play in testicular descent, is richly supplied by the genital branch of the genitofemoral nerve through its scrotal attachment. In neonatal rats the genitofemoral nerve overlying the psoas muscle was divided before inguinal descent would normally occur, and the effect of this procedure on subsequent testicular descent was observed. Denervation of the gubernaculum caused the testes to remain in the abdomen. The significance of this finding in the rat is that an intact genitofemoral nerve is an essential prerequisite for normal descent, perhaps by allowing the gubernaculum to evert. PMID- 2883966 TI - A Bacteroides nodosus pili vaccine produced by recombinant DNA for the prevention and treatment of foot-rot in sheep. PMID- 2883967 TI - Dipeptidyl peptidase IV in human T lymphocytes. An approach to the role of a membrane peptidase in the immune system. AB - Dipeptidyl peptidase IV (DP IV), an ectoenzyme in the cell membrane of human T lymphocytes, is an important constituent in the process of lymphocyte activation and proliferation. In the presence of specific inhibitors and antibodies against DP IV several in vitro functions of activated lymphocytes were found to be impaired. These include mitogen induced DNA synthesis, immunoglobulin secretion and production of interferon-gamma. The functional importance of DP IV during activation of lymphocytes is underlined by an increase in cellular DP IV activity upon mitogenic stimulation. PMID- 2883968 TI - Inhibition by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, of enzyme induction by glucocorticoid and of nuclear translocation of glucocorticoid-receptor complexes. AB - Induction of tyrosine aminotransferase by glucocorticoid in rat hepatocytes was inhibited concentration-dependently by 1-(5-isoquinolinesulfonyl)-2 methylpiperazine dihydrochloride (H-7), an inhibitor of protein kinase C, but not by N- [2-(methyl-amino)-ethyl]-5-isoquinolinesulfonamide dihydrochloride, an inhibitor of cyclic nucleotide dependent protein kinases. H-7 also inhibited the accumulation of glucocorticoid-receptor complexes in the nuclear fraction with associated accumulation of these complexes in the cytoplasmic fraction, but did not affect incorporation of glucocorticoid into hepatocytes. These results indicate that protein kinase C may be essential in translocation of glucocorticoid-receptor complexes to the nuclei. PMID- 2883969 TI - Purification and characterization of two types of atrial natriuretic factor receptors from bovine adrenal cortex: guanylate cyclase-linked and cyclase-free receptors. AB - Atrial natriuretic factor (ANF) receptors with and without guanylate cyclase activity were simultaneously purified to apparent homogeneity from bovine adrenal zona glomerulosa cell membrane fractions. The particulate guanylate cyclase which co-purified with the ANF receptor showed one of the highest specific activity reported. The receptors with or without the guanylate cyclase activity showed high affinities to ANF (99-126). The receptor without the cyclase showed a high affinity to truncated ANF analogs, ANF (103-123) and ANF (105-121), whereas the cyclase-linked receptor had a much lower affinity to these analogs. Both of the receptors migrated as a single band with a molecular weight of 135,000 daltons on SDS-gel electrophoresis under non-reducing conditions. The 135,000 daltons band of the receptor without the cyclase was shifted to a 62,000 daltons band under reducing conditions, but the band for the cyclase-linked receptor was not shifted. These results demonstrated the presence of two subtypes of ANF receptor in bovine adrenal cortex and indicate two different modes of intracellular action of ANF. PMID- 2883971 TI - A direct evidence for the involvement of poly(A) in protein synthesis. AB - A radioactive polyadenylated globin mRNA was translated in either rabbit reticulocyte lysate or wheat germ extract under various conditions. When globin mRNA was translated, globin synthesis was directly proportional to the rate of loss in A units from the poly(A) tail. On the other hand, when globin poly(A) mRNA was incubated under non-translated conditions, no loss of A units was detected. The presence of ribonuclease inhibitor in the reaction mixture did not alter either the rate of globin synthesis or the loss in A units from the poly(A) tail. The present data suggests a correlation between protein synthesis and loss in A units from the poly(A) tail. PMID- 2883970 TI - Platelet factor XIII is activated by calpain. AB - The action of calpain (EC 3.4.22.17; Ca2+-dependent cysteine proteinase) on platelet factor XIII has been studied. Calpain I activated platelet factor XIII up to 76% of the maximum level observed with thrombin. Activation was accompanied by the limited proteolysis of the a subunit of platelet factor XIII to produce a 76 kDa fragment which was comparable to the proteolytic product by thrombin. Activation of platelet factor XIII by calpain was inhibited by EDTA, leupeptin, and endogenous calpain-specific inhibitor calpastatin. These findings suggest that calpain is responsible for the intracellular activation of platelet factor XIII. PMID- 2883972 TI - Biochemical and proton NMR characterization of the isolated functional beta subunit of coupling factor one from spinach chloroplasts. AB - Beta subunits have been dissociated from CF1 of spinach chloroplasts, purified by HPLC and characterized by two-dimensional electrophoresis and fluorescence emission. The solutions of isolated beta subunits are able to hydrolyze MgATP; this ATPase activity is an intrinsic property of the beta molecule. From proton NMR at 300 and 500 MHz, it is shown that the preparations are fully reproducible and that beta subunits remain monomeric with 75% aliphatic protons associated with rigid parts of the molecule. The other 25% give rise to separate resonances and belong to mobile side-chains and/or to flexible regions. The measurement of the transverse relaxation times T2 has permitted a detailed characterization of the molecular dynamics of the isolated beta subunits. PMID- 2883974 TI - Human liver cDNA clones encoding proteolipid subunit 9 of the mitochondrial ATPase complex. AB - Clones encoding the proteolipid subunit 9 of the mitochondrial ATPase complex have been isolated from a lambda gt10 library of human liver cDNA sequences, using a probe of Neurospora crassa cDNA encoding subunit 9. From nucleotide sequence analysis it is concluded that the amino acid sequence of mature human subunit 9 is identical to that of its bovine counterpart. By comparing the sequence of two cDNA clones (denoted human 1 and 2) to those of two bovine cDNA clones (denoted P1 and P2) recently described by Gay and Walker (EMBO J. 4, 3519 3524, 1985) it is evident that there are close sequence relationships between human 1 and bovine P1, and between human 2 and bovine P2, although both human clones are truncated at their 5'-ends. Thus, as in bovine cells there appears to be at least two human genes encoding subunit 9. PMID- 2883973 TI - Different mechanisms control developmental activation of transcription of genes subject to identical hormonal regulation in adult liver. AB - Developmental changes in expression of two genes subject to identical hormonal controls in adult liver were examined in livers of fetal and newborn rats. Both mRNA concentrations and transcription of tyrosine aminotransferase were very low throughout gestation and increased sharply at birth. The mRNA of gene 33 (Lee et al., J. Biol. Chem. 260: 16433-16438, 1985) and its transcription were also low in fetal liver until a significant increase occurred just prior to birth, followed by a further increase at birth. In mutant mice carrying a deletion that prevents developmental activation of aminotransferase transcription, that of gene 33 was not affected. The data indicate that different mechanisms control developmental activation of these genes, in contrast to hormonal regulation of their expression. PMID- 2883975 TI - Protein ligand interactions. Indole alkaloids as inhibitors for lactate dehydrogenase. AB - Kinetic analysis showed that the indole alkaloids strychnine and brucine interact competitively with the enzyme lactate dehydrogenase with respect to the substrate pyruvate and non competitively with respect to NADH. Since the alkaloids possess a potential enolate and a quaternary nitrogen they bridge the binding sites for the substrates - pyruvate and NAD+. Conformational alterations induced by the binding of ligands to the enzyme subunits are discussed in terms of the proposed chemical model. PMID- 2883976 TI - Inhibitors of inosinate dehydrogenase. AB - Inosinate dehydrogenase (IMP-dehydrogenase) from Chinese Hamster Ovary cells was found to be inhibited by two types of inhibitors. One type of inhibitor binds competitively at IMP-binding site and other type at NAD-binding site of the enzyme. Some new inhibitors of both classes have been illustrated here and their inhibition constants and type of inhibition determined. NAD-analog of tiazofurin was found to bind with both the sites and this type of inhibitors were found to be non-competitive with IMP and NAD. PMID- 2883977 TI - Receptor-stimulated inositol phospholipid hydrolysis and neural function. AB - Many transmitters in the brain act by stimulating the hydrolysis of an inositol lipid (phosphatidylinositol 4,5-bisphosphate) to give diacylglycerol (DG) and inositol 1,4,5-trisphosphate (Ins1,4,5P3). These two second messengers mark the beginning of a highly versatile signalling system which may have a unique role in modulating neural activity. By mobilizing calcium from intracellular stores, Ins 1,4,5P3 may regulate the calcium set-point thereby effecting both excitability and facilitation. The DG/C-kinase pathway, through its ability to modulate a variety of physiological processes, may regulate both transmitter release and excitability. Some of the changes in excitability seem to depend upon changes in potassium permeability. Receptor-stimulated inositol lipid hydrolysis may thus play a central role in neural function by modulating transmitter release through subtle alterations in excitability. PMID- 2883978 TI - Takayasu's arteritis associated with crescentic glomerulonephritis. AB - We describe the initial course and followup of a 16-year-old white female patient who presented in 1983 with aortitis and rapidly progressive renal failure. Renal biopsy revealed crescentic glomerulonephritis. Segmental occlusions of the distal aorta and both common iliac arteries were demonstrated on aortography. Initially, her renal function and arterial occlusions markedly improved with pulse prednisolone therapy, but 34 months later, the glomerulonephritis and aortitis worsened. This case report, the first of its kind, documents both the association of Takayasu's arteritis with crescentic glomerulonephritis and a marked, though incomplete, response to pulse therapy. PMID- 2883979 TI - [Biotransformation and pharmacokinetics of bamipine in rats. 2. Studies of the pharmacokinetics (1.)]. AB - Biotransformation and Pharmacokinetics of Bamipine in Rats/2nd Communication: Pharmacokinetic studies (Part I). After oral application in Wistar rats the pharmacokinetic properties of N-phenyl-N-benzyl-4-amino-1-methylpiperidine (bamipine) were investigated. The compound is quantitatively absorbed. Bamipine distribution occurs in the whole organism. A transient accumulation was found in liver, kidney, spleen and lung. The compound's liquor patency was established. The elimination is mainly renal (85.81%), 13.23% are eliminated by feces. The total excretion after 96 h is more than 99%. PMID- 2883980 TI - Plasma levels and pharmacokinetics of single and multiple dose of tetrazepam in healthy volunteers. AB - The pharmacokinetics of tetrazepam (Myolastan, Musaril), were studied in 12 healthy volunteers. Tetrazepam was given orally as a single dose of 50 mg and repeated administration for 5 consecutive days of 50 mg at 12-h intervals, in tablet form. Tetrazepam was measured in plasma using a selective and sensitive GLC method. Tetrazepam is rapidly absorbed after oral administration with a peak plasma level of 0.49 +/- 0.10 mg/l at 0.94 +/- 0.47 h. The drug is widely distributed in the organism with an apparent volume of distribution of 6.7 +/- 2.1 l/kg. Tetrazepam is eliminated with a half-life of 22 +/- 4 h and can be classified as a benzodiazepine with medium half-life value. This medium half-life is the result of the high hepatic clearance of the drug in spite of its large distribution volume. Since in this study 6 male and 6 female volunteers were studied it was possible to compare the pharmacokinetic profile in the two groups. No significant differences were observed. No differences were observed between the pharmacokinetic values after a single dose or after repeated administration. PMID- 2883981 TI - Effect of etersalate on human platelet responsiveness. A study in healthy volunteers. AB - Ex vivo antiplatelet properties of 2-(p-acetamido-phenoxy)ethyl-o-acetoxybenzoate (etersalate, Daital) and its effects on serum thromboxane A2 (TXA2) levels and prostaglandin I2 (PGI2) generation were studied in human volunteers at two levels of oral dosing. Etersalate inhibited at the lower dosage platelet function and decreased TXA2 levels, but PGI2 generation from rat aortic rings was stimulated when incubated with plasma from etersalate-treated donors. Blood coagulation parameters remained within normal values. It is suggested that etersalate administration could act on platelet arachidonate metabolism at a different level than that of the cyclooxygenase pathway. PMID- 2883983 TI - Correlation between biological state markers of alcohol abuse and severity of alcohol dependence syndrome. AB - Data on the correlation between the degree of severity of the alcohol dependence syndrome, as evaluated through the Short Alcohol Dependence Data (SADD) questionnaire, and alterations of four biological state markers of alcohol abuse, namely gamma-glutamyltransferase (GGT), glutamate pyruvate transaminase (SGPT), glutamate oxalacetate transaminase (SGOT) and mean corpuscular volume (MCV), in a sample of 137 alcoholics, are presented. A significant increase in the proportion of altered GGT and SGOT results was found in those patients with higher scores in the SADD. The analysis of the correlation (Spearman coefficient) between the values of each biological test and the SADD scores showed only a significant, though low, positive correlation for SGOT (r = 0.29). PMID- 2883982 TI - Investigations into the neuropharmacological basis of temporal stages of memory formation in mice trained in an active avoidance task. AB - The memorial effects of glutamate, LaCl3, ouabain, or anisomycin injection around the time of active avoidance training in mice were assessed in this study. Based on the Gibbs and Ng hypothesis of memory formation in chicks (Biobehav. Rev., 1 [1977] 113-136), it was predicted that these pharmacological agents would not only induce significant amnesia but, more specifically, short duration memory should be selectively impaired by glutamate and LaCl3, intermediate duration memory should be impaired by ouabain, and anisomycin should affect only long lasting memories. Results of the experiments described below indicate these drugs are potent inhibitors of memory formation in rodents. In addition, LaCl3-induced amnesia was fully prevented by CaCl2. However, the mechanism by which glutamate and ouabain affected memory may not be exactly as described by Gibbs and Ng: gamma-D-glutamylglycine and diphenylhydantoin did not completely prevent glutamate- and ouabain-induced amnesias, respectively. Finally, all amnestic agents induced amnesia that developed within minutes of training, and the time course of development of amnesia for each drug could not be distinguished from one another. These data are discussed in terms of their implications for the Gibbs and Ng model of memory formation. PMID- 2883984 TI - Oral sedation with temazepam: controlled comparison of a soft gelatin capsule formulation with intravenous diazepam. PMID- 2883985 TI - Beta-adrenoceptor blockade, alpha-stimulation and changes in plasma potassium concentration after suxamethonium administration in dogs. AB - A study involving 20 mongrel dogs tested the hypotheses that beta-adrenoceptor blockade or alpha-adrenoceptor stimulation may potentiate and prolong the increase in plasma potassium concentration after suxamethonium administration, and that the beta effect is beta 2-receptor mediated. Propranolol 0.5 mg kg-1 altered the time to peak increase in plasma concentration of potassium after suxamethonium, but did not increase peak concentrations. In controls, the maximum change (0.83 mmol litre-1) occurred at 3 min, while in propranolol-treated dogs the peak change (0.96 mmol litre-1 occurred at 30 min. Similar results were obtained when metoprolol 0.25 mg kg-1 and ICI 118551 0.1 mg kg-1 were used, respectively, as selective beta 1- and beta 2-adrenoceptor blockers. The increases in potassium concentration following suxamethonium in the metoprolol group (0.98 mmol litre-1) and the ICI 118551 group (0.82 mmol litre-1) reached maximum concentrations at 30 min compared with the controls (0.79 mmol litre-1) which achieved a maximum at 3 min. Phenylephrine was infused at 8 micrograms kg-1 min-1 to produce alpha stimulation. The infusion alone altered plasma concentrations of potassium, but the haemodynamic changes were such that conclusions as to the effect of alpha-stimulation on release of potassium after suxamethonium could not be reached. PMID- 2883986 TI - Comparative neuromuscular blocking effects of vecuronium, pancuronium, Org 6368 and suxamethonium in the anaesthetized domestic pig. AB - The neuromuscular blocking and cardiovascular effects of three competitive neuromuscular blocking drugs, vecuronium, pancuronium and Org 6368, and the depolarizing drug suxamethonium, have been evaluated in the anaesthetized domestic pig. Both the relative time-course and the order of potency of the drugs agreed well with published data in man. In addition, the cardiovascular side effects of pancuronium and Org 6368 were identified readily. These preliminary results suggest that the pig may provide more reliable neuromuscular blocking time-course data than does the more commonly utilized cat model. PMID- 2883989 TI - Beta blockers in pregnancy. PMID- 2883987 TI - Effects of beta-adrenoceptor blockade on heart rate and physiological tremor in diabetics with autonomic neuropathy. A comparative study of epanolol, atenolol and pindolol. AB - Eight diabetics with autonomic neuropathy were given single oral doses of epanolol (200 mg), atenolol (50 mg), pindolol (5 mg) and placebo in a double blind randomised order at weekly intervals. Supine resting heart rate, physiological tremor and blood glucose were measured before, 2 and 4 h after dosing, and ambulatory heart rate monitored for 24 h. Supine resting heart rate was significantly lowered by atenolol both at 2 and 4 h, and increased on pindolol at 4 h. Heart rate was unaffected by epanolol compared with placebo. Heart rate during the 'waking' period (14.00-23.00 h) was lower than placebo after epanolol and atenolol but unaffected by pindolol. During the 'sleeping' period (23.00 h-08.00 h) heart rate was significantly increased by pindolol, lowered with atenolol and unaffected on epanolol. Pindolol significantly increased physiological tremor at 4 h. No differences were seen between epanolol, atenolol and placebo. Plasma glucose was significantly increased by pindolol 2 h after dosing. These results suggest that pindolol probably produces its partial agonist activity at both beta 1- and beta 2-adrenoceptors, while the partial agonist activity of epanolol is beta 1-selective. Despite abnormal cardiovascular reflex tests in these diabetics, the heart rate responses obtained in this study after beta-adrenoceptor blockade were surprisingly normal, and suggest that the concept of 'cardiac denervation' in diabetes requires modification. PMID- 2883988 TI - The assessment in man of the beta-adrenoceptor blocking activity and cardioselectivity of H-I 42 BS, a long acting beta-adrenoceptor blocking drug. AB - The pharmacokinetic and pharmacodynamic effects of the beta-adrenoceptor antagonist H-I 42 BS were examined in healthy subjects. In an open dose ranging study, H-I 42 BS 50, 100, 200 and 400 mg were given as single oral doses to four subjects. H-I 42 BS 400 mg caused maximum reduction in exercise heart rate (20.4 +/- 1.0%--mean +/- s.d.) at 4 h and still reduced exercise heart rate at 96 h (18.4 +/- 7.2%). Seven subjects received in double-blind, randomised order, single oral doses of H-I 42 BS 50, 100 and 200 mg, atenolol 50 and 100 mg and placebo. H-I 42 BS 400 mg was given in a single blind manner as the last dose of the study. Both H-I 42 BS and atenolol reduced supine and standing heart rate and systolic blood pressure (P less than 0.05) although atenolol had the more marked effect. The maximum percent reduction of exercise heart rate after H-I 42 BS 50 mg was 10.9 +/- 7.1%, after 100 mg was 18.7 +/- 5.8%, after 200 mg was 20.6 +/- 6.4% and after 400 mg was 21.9 +/- 8.2%. H-I 42 BS 400 mg still caused 11.0 +/- 3.5% reduction at 168 h. Atenolol 50 mg caused maximum percent reduction of exercise heart rate of 26.0 +/- 6.0% but did not reduce exercise heart rate after 24 h. The mean peak plasma concentrations for all doses of H-I 42 BS occurred at 5.1 +/- 1.5 h. The plasma elimination half-life was 47.6 +/- 8.1 h. There was a linear correlation between the dose and AUC0-infinity (r = 0.97). The cardioselectivity of H-I 42 BS and atenolol was compared. Six subjects received in double-blind random order H-I 42 BS 100 and 400 mg, atenolol 50 mg and placebo. After each dose, graded infusions of isoprenaline were given until the heart rate increased by 50 beats min-1. Dose-response curves for heart rate, diastolic blood pressure, forearm blood flow and finger tremor were constructed. There was no difference in the dose-response curves for forearm blood flow or finger tremor after H-I 42 BS 400 mg or atenolol 50 mg. Atenolol 50 mg caused more attenuation (P less than 0.01) of the diastolic blood pressure response. These results indicate that H-I 42 BS is a cardioselective beta-adrenoceptor antagonist with a long duration of action in man. PMID- 2883990 TI - Levobunolol and metipranolol: comparative ocular hypotensive efficacy, safety, and comfort. AB - Topical levobunolol 0.5% was compared with topical metipranolol 0.6% for efficacy, safety, and comfort in 46 patients with open angle glaucoma or ocular hypertension. The study was of parallel design, randomised, double-masked, and of three months' duration. After a washout interval the study medications were instilled twice daily in both eyes. The overall mean decrease in intraocular pressure (IOP) was approximately 7 mmHg in both groups. More than 90% of patients in both groups successfully completed the study. Both agents caused slight decreases in heart rate and blood pressure. More complaints of burning and stinging were reported in the metipranolol group than in the levobunolol group. This three-month, 46-patient study showed levobunolol 0.5% and metipranolol 0.6% to be similarly effective ocular hypotensive agents. PMID- 2883991 TI - Inhibition of yeast mitochondrial F1-ATPase, F0F1-ATPase and submitochondrial particles by rhodamines and ethidium bromide. AB - ATP hydrolysis by F1-ATPase is strongly inhibited by cationic rhodamines; neutral rhodamines are very poor inhibitors. Rhodamine 6G is a noncompetitive inhibitor of purified F0F1-ATPase and submitochondrial particles, however, an uncompetitive inhibitor of F1-ATPase (KI approximately equal to 2.4 microM for all three enzyme forms). Ethidium bromide is a noncompetitive inhibitor of F0F1-ATPase, submitochondrial particles and also F1-ATPase (KI approximately equal to 270 microM). Neither of the inhibitors affects the negative cooperativity (nH approximately equal to 0.7). The non-identical binding sites for rhodamine 6G and ethidium bromide are located on the F1-moiety and are topologically distinct from the catalytic site. Binding of the inhibitors prevents the conformational changes essential for energy transduction. It is concluded that the inhibitor binding sites are involved in proton translocation. In F1-ATPase, binding of MgATP at a catalytic site causes conformational changes, which allosterically induce the correct structure of the rhodamine 6G binding site. In F0F1-ATPase, this conformation of the F1-moiety exists a priori, due to allosteric interactions with F0-subunits. The binding site for ethidium bromide on F1-ATPase does not require substrate binding at the catalytic site and is not affected by F0F1 subunit interactions. PMID- 2883992 TI - Electron-microscopic studies on location of SH-groups in mitochondrial F1-ATPase using a ferritin label. AB - A new approach has been suggested for electron-microscopic study of the structure of mitochondrial F1-ATPase based on ferritin labeling. By means of sequential treatment with 2-iminothiolane and Nbs2 we obtained a modified ferritin (NbsSPrCNH-Ft) able to react with SH-groups of proteins and to form conjugates in which the protein and ferritin are bound by disulfide bonds. An electron microscopic investigation of the negatively stained preparations of mitochondrial F1-ATPase, preincubated with modified ferritin, revealed such enzyme-ferritin conjugates. In case of modified ferritin, containing 360 mol SH-groups per mol protein, and F1-ATPase, pretreated with N-ethylmaleimide and then with dithiothreitol, conjugates were obtained in which ferritin molecules are bound to several (as many as four) of the six protein masses, comprising a bilayer molecule of the enzyme. Taking into consideration the biochemical data on the location of accessible SH-groups (only in alpha, gamma or epsilon subunits), it is inferred from the results obtained that one of the protein masses is a complex between beta subunit and at least one of the minor subunits located partially on the molecule's external side. This indicates the nonequivalence of different copies of the major subunits. Averaged images of the particles of the F1-F0 complex from bovine heart mitochondria and bacteria Micrococcus lysodeicticus were obtained. It was found that F0 component is bound to two adjacent protein masses of the F1-ATPase molecule. It is suggested that this binding may be due the nonequivalency of single-type major subunits. PMID- 2883993 TI - Novel approaches towards characterization of the high-affinity nucleotide binding sites on mitochondrial F1-ATPase by the fluorescence probes 3'-O-(1 naphthoyl)adenosine di- and triphosphate. AB - The fluorescence properties of 3'-O-(1-naphthoyl)adenosine di- and triphosphates (termed N-ADP and N-ATP, respectively) were investigated in detail. Of special importance for the use of these analogues as environmental probes is their high quantum yield (0.58 in water) and the polarity dependence of shape and wavelength position of the emission spectrum. Upon binding of N-ADP and N-ATP to mitochondrial F1-ATPase, the fluorescence intensity is markedly decreased, due to polarity changes and 'ground-state' quenching. Using this signal for equilibrium binding studies, three (at least a priori) equivalent nucleotide-binding sites were detected on the enzyme. The perspective intrinsic dissociation constants are as follows: N-ADP/Mg2+ 120 nM; N-ATP/Mg2+ 160 nM; N-ADP/EDTA 560 nM; N-ATP/EDTA 3500 nM. For bound ligand the environment was found to be rather unipolar; the rotational mobility of the fluorophore is restricted, its accessibility for iodide anions (as a quencher) is hindered. These facts show a location of the binding sites quite deeply embedded in the protein. The conformation of the binding domains is strongly dependent on the absence or presence of Mg2+, as can be seen from the relative efficiencies of the singlet-singlet energy transfer from tyrosine residues in the protein to bound naphthoyl moieties. Investigation of the binding kinetics revealed this process as biphasic (in presence of Mg2+). After the first fast step (kon greater than 1 X 10(6) M-1 X s-1), in which the analogue is bound to the enzyme, a slow local conformational rearrangement occurs. PMID- 2883994 TI - Electrochemical potential and ion transport in vesicles of yeast plasma membrane. AB - Vesicles from yeast plasma membrane were prepared according to Franzusoff and Cirillo [1983) J. Biol. Chem. 258, 3608), with slight modifications. When Mg-ATP was added, this preparation was able to generate a membrane potential, that was sensitive to inhibitors of the yeast H+-ATPase and uncouplers, and could be decreased by the addition of permeant anions, as measured by the fluorescence changes of the dye oxonol V. The addition of ATP could also generate a pH gradient, detectable by the fluorescence changes of the monitor aminochloromethoxyacridine. This gradient was sensitive to inhibitors of ATPase and uncouplers, and could be increased by the addition of permeant anions to the incubation mixture. When the vesicles were loaded with KCl, an increased rate of K+ efflux was produced upon the addition of ATP. Cytochrome oxidase from bovine heart could be reconstituted into the vesicles and was shown to generate a membrane potential difference, negative inside, evidenced by the fluorescence quenching of the cyanide dipropylthiacarbocyanine and the uptake of tetraphenylphosphonium. Besides, in these vesicles, K+ and Rb+, but not Na+ or NH+4 could decrease the quenching of fluorescence and the uptake of tetraphenylphosphonium produced when the electron-donor system was present. In the vesicles in which cytochrome oxidase was incorporated, upon the addition of cytochrome c and ascorbate, the uptake of 86Rb+ could be demonstrated also. This uptake was found to be saturable and inhibited by K+, and to a lesser degree by Na+. The results obtained indicate that these vesicles are reasonably sealed and capable of generating and maintaining a membrane potential. The membrane potential could be used to drive ions across the membrane of the vesicles, indicating the presence and functionality of the monovalent cation carrier. The vesicles, in general terms seem to be suitable for studying transport of ions and metabolites in yeast. PMID- 2883995 TI - [The species composition of phytoplankton and its consumption at breeding sites for blood-sucking mosquitoes]. AB - The phytoplankton specific composition and the character of its consumption by larvae of blood-sucking mosquitoes have been determined. Blue-green (5 species), green (13 species), Euglenophyta (12 species) and diatoms (38 species) algae have been found in the breeding places of Culicidae. The diatoms prevailed in the food of larvae. Trophic specialization to the definite food components have not been found in larvae. Their intestines contained detritus, zooplankton and other components besides phytoplankton. PMID- 2883996 TI - Testicular modulation of luteinizing hormone response to gonadotropin-releasing hormone (GnRH)-agonist treatment. AB - We and others have observed that the response of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to chronic gonadotropin-releasing hormone agonist (GnRH-A) treatment is substantially different in normal compared to hypogonadal males. These data suggested that products of the testes determine the gonadotropin response to GnRH-A. The present studies were designed to determine whether this effect is mediated by products of the interstitial (steroids) or the tubular compartment. To create experimental states with selective impairment of interstitial, tubular, or both compartments, 100 male sexually mature Wistar rats were divided into five groups: I, intact; II, castrated; III, castrated with 20 mm testosterone (T) implants; IV, bilaterally cryptorchid; and V, ketoconazole treated animals. Cryptorchid animals have been shown to have impairment of tubular function while ketoconazole inhibits T biosynthesis. Each of the 5 groups was divided into 2 subgroups to receive daily injections of either saline or 1 microgram of a potent GnRH agonist, D-leu6 des-Gly10 GnRH N-ethylamide, for 4 wk. Unlike the intact animals, which showed an elevation of basal serum LH concentration after 4 wk of GnRH-A treatment, the castrated animals showed significant suppression below baseline. Animals with preferential impairment of tubular function (cryptorchid and castrated + T) also showed significant suppression of LH after GnRH-A treatment. However, the ketoconazole-treated animals (with inhibition of T biosynthesis and intact tubular function), behaved similarly to intact animals and demonstrated an elevation of LH after GnRH-A treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2883997 TI - Induction of mouse oocyte maturation in vivo by perturbants of purine metabolism. AB - Previous studies have suggested a critical role for purines in the maintenance of mouse oocytes in meiotic arrest. If so, then disrupting specific purine metabolic pathways in vivo might induce the resumption of oocyte maturation. To test this hypothesis, immature mice were primed with pregnant mare's serum gonadotropin and 24 h later received, by i.p. injection, one of several drugs that inhibit specific enzymes in the purine metabolic pathways. Cumulus cell-enclosed oocytes were isolated from the ovaries at varying times after drug treatment and assessed for germinal vesicle breakdown (GVBD). The inosine monophosphate dehydrogenase inhibitors, mycophenolic acid (MA) and bredinin (Br), each induced GVBD in a dose dependent fashion, Br being the more effective agent. When the kinetics of oocyte maturation were examined, 71% of the oocytes from MA-treated mice had undergone GVBD 21-22 h after drug administration. Moreover, 100% GVBD was observed in oocytes from Br-treated mice after 6 h. The action of these drugs appeared to be a direct one and not mediated through stimulation of pituitary gonadotropin release or atresia. Azaserine, an inhibitor of de novo purine synthesis, also induced GVBD in a dose-dependent manner. However, sodium hadacidin and dl alanosine, inhibitors of adenylosuccinate synthetase, failed to elicit a maturational response in oocytes in vivo. These data support an essential role for guanyl and/or xanthyl derivatives in the maintenance of meiotic arrest in vivo. PMID- 2883998 TI - Transcriptional induction of cellular gene expression during lytic infection with herpes simplex virus. AB - Herpes simplex virus Type 2 causes a severe repression of host cell biosynthesis at a number of levels. We show that despite this, non-viral cDNA clones derived from cellular RNA species which accumulate to high levels after infection can be isolated using differential screening techniques. By using nuclear run-off assays, we have shown that this RNA accumulation is mediated by transcriptional induction of the corresponding cellular genes. PMID- 2883999 TI - Effect of ligation of common bile duct on somatostatin levels and binding in cytosol of rabbit duodenal mucosa. AB - Rabbits with ligation of the common bile duct, of one and three weeks duration, showed a significant increase of somatostatin content in duodenal mucosa and plasma as compared with control animals. The increase of mucosal somatostatin was associated with a decrease in the binding capacity of both high- and low-affinity binding sites without changes in the affinity values in cytosol of duodenal mucosa. These findings suggest that the number of somatostatin binding sites is inversely related to local levels of the peptide and support the hypothesis of somatostatin regulating its own binding sites. PMID- 2884000 TI - Transfusion-associated AIDS: donor-recipient human immunodeficiency virus exhibits genetic heterogeneity. AB - The genetic diversity of the human immunodeficiency virus (HIV) isolated from transfusion-associated AIDS patients has been examined. Restriction enzyme mapping studies of integrated proviral DNA of donor and recipient origin demonstrated genomic variation between isolates. Analysis of the molecularly cloned viral genomes of one donor-recipient pair showed that virus from the recipient had restriction enzyme site differences from the donor, noticeably clustered in the env and orf-2 regions, and also had a greater number of restriction sites in common with the donor as well. These results suggest that HIV may undergo genomic variation in vivo. Comparison of donor-recipient viruses may further the understanding of the molecular basis for AIDS pathogenesis. PMID- 2884001 TI - Studies of the antigenic activity of Entamoeba histolytica extracts. PMID- 2884002 TI - Benzodiazepine abuse. AB - Benzodiazepine abuse is indicated by excessive and long-term consumption, particularly by the elderly. Side-effects associated with long-term use are reviewed with special reference to the problem of dependence. Factors predictive of such dependence are examined and procedures for its management are described. PMID- 2884003 TI - Glutamate-evoked release of endogenous brain dopamine: inhibition by an excitatory amino acid antagonist and an enkephalin analogue. AB - The present study examined the effect of a selective delta-opioid receptor agonist [D-Ala2-D-Leu5] enkephalin (DADL) on the spontaneous and the L-glutamic acid (L-Glu)-evoked release of endogenous dopamine from superfused slices of rat caudate-putamen. The amount of dopamine in slice superfusates was measured by a sensitive method employing high-performance liquid chromatography with electrochemical detection (h.p.l.c.-e.d.) after a two-step separation procedure. The spontaneous release of endogenous dopamine was partially dependent on Ca2+, enhanced in Mg2+-free superfusion medium, partially reduced by tetrodotoxin (TTX, 0.3 microM), partially reduced by the putative excitatory amino acid receptor antagonist DL-2-amino-7-phosphonoheptanoic acid (DL-APH, 1 mM), and increased 10 fold by the dopamine uptake blocker, nomifensine (10 microM). DADL (5 and 50 nM) did not significantly affect spontaneous dopamine release. L-Glu (0.1-10 mM) produced a concentration-dependent release of endogenous dopamine from slices of caudate-putamen. This effect was Ca2+-dependent, strongly inhibited by 1.2 mM Mg2+, attenuated by DL-APH (1 mM), attenuated by TTX (0.3 microM), and enhanced by nomifensine (10 microM). In the presence of nomifensine DADL (50 nM) reduced significantly the L-Glu-evoked release of endogenous dopamine by 20%. The inhibitory effect of DADL was blocked by 10 microM naloxone. These results indicate that L-Glu stimulates the Ca2+-dependent release of endogenous dopamine in the caudate-putamen by activation of N-methy-D-aspartate-type of excitatory amino acid receptors. This release can be selectively modified by the delta opioid agonist DADL in a naloxone-sensitive manner. PMID- 2884004 TI - Four motor effects of capsaicin on guinea-pig distal colon. AB - The motor effects of capsaicin on the guinea-pig distal colon have been investigated in vivo and in vitro. Capsaicin (0.1-10 micrograms kg-1 i.v.) produced a transient relaxation which was reduced by pretreatment with capsaicin itself, atropine, hexamethonium, phentolamine or guanethidine and almost abolished by tetrodotoxin (TTX). Topically applied capsaicin produced a transient inhibition of tone and spontaneous activity prevented by topically applied TTX. In isolated preparations of distal colon, capsaicin produced a transient, TTX- and atropine-sensitive contraction which was followed by a depression of the contractile activity. The depressant effect was unaffected by atropine plus guanethidine but was greatly reduced by TTX, indicating activation of intramural non-adrenergic, non-cholinergic (NANC) mechanisms. The depressant effect on the first exposure to capsaicin (1 microM) was greater than that produced by a second, third or fourth exposure. In preparations excised from capsaicin pretreated animals, capsaicin (1 microM) only produced an inhibitory effect on spontaneous contractions. Desensitization did not occur to this inhibitory effect. In preparations pre-exposed to capsaicin (1 microM, 1 h before), capsaicin (1-30 microM) produced a concentration-related inhibition of spontaneous contractions (IC50 = 19 microM) and of the high K+-induced tonic contraction (IC50 = 23 microM). A similar effect on spontaneous motility was produced by capsaicin in colonic segments excised from capsaicin-pretreated guinea-pigs (IC50 = 16 microM) or guinea-pigs treated with TTX (IC50 = 20 microM). It is concluded that, in vivo, capsaicin activates inhibitory reflexes, presumably due to stimulation of primary afferent fibres. This effect involves, at least in part, activation of sympathetic nerves to this organ. The contractile effect of capsaicin on the isolated colon involves activation of intramural cholinergic neurones, whereas the TTX-sensitive component of the inhibitory effect involves either release of an inhibitory transmitter through an axon reflex arrangement or activation of NANC neurones. In addition, at high concentrations capsaicin produces a direct depression of smooth muscle contraction. PMID- 2884005 TI - Tyr-MIF-1 attenuates antinociceptive responses induced by three models of stress analgesia. AB - Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), a biologically active brain peptide, has previously been shown to antagonize the analgesia induced by morphine. In this report experiments are described in which mice were tested on the hot-plate in three models of antinociception - shock, novel environment, and warm-water swim - after the administration of various doses of Tyr-MIF-1 without any exogenous opiates. The peptide reduced the antinociception produced by all three methods of inducing endogenous antinociception. These results add further support for the existence of peptides like Tyr-MIF-1 that act as opiate antagonists. PMID- 2884007 TI - Inhibitory responses to nicotine and transmural stimulation in hyoscine-treated guinea-pig isolated trachealis: an electrical and mechanical study. AB - Guinea-pig isolated trachealis muscle treated with hyoscine (1 microM) exhibited mechanical tone which could be suppressed by transmural stimulation and, in a concentration-dependent manner, by nicotine (10-1000 microM). Hexamethonium (500 microM) did not itself cause tone changes, antagonized effects of nicotine but did not antagonize those of isoprenaline. Tetrodotoxin (0.3 microM) did not itself cause tone changes, did not modify the action of isoprenaline but antagonized the effects of nicotine and very markedly reduced responses to transmural electrical stimulation. Guanethidine (50 microM) did not itself cause tone changes, potentiated the action of isoprenaline, antagonized effects of nicotine and reduced responses to transmural electrical stimulation. Propranolol (1 microM) did not itself cause tone changes, antagonized effects of both isoprenaline and nicotine and reduced responses to transmural electrical stimulation. Propranolol (10 microM) caused greater antagonism of isoprenaline but did not further antagonize nicotine or further reduce responses to electrical stimulation. Intracellular electrophysiological recording from hyoscine-treated trachealis showed that 10 microM nicotine caused little or no mechanical or electrical change. Higher concentrations (100 microM and 1 mM) evoked relaxation which was often though not invariably accompanied by transient hyperpolarization and transient inhibition of electrical slow waves in the impaled cell. Hexamethonium (500 microM), tetrodotoxin (0.3 microM), guanethidine (50 microM) and propranolol (1 microM) each suppressed the electrical or mechanical changes evoked by nicotine (100 microM). However, nicotine (1 mM) tested in the presence of propranolol (1 microM), caused relaxation which could be accompanied by slow wave suppression but not by change in resting membrane potential. Transmural stimulation of hyoscine-treated trachea with single pulses of supramaximal voltage and 0.5 ms duration evoked neither relaxation nor membrane potential changes. Stimulation with similar pulses in trains of 5 s duration evoked relaxation which was dependent on pulse frequency. In many cells this relaxation was not accompanied by membrane potential change. In other cells suppression of slow waves occurred. At high pulse frequencies (greater than 16 Hz) this was generally accompanied by membrane hyperpolarization. In tissue treated with hyoscine and propranolol (both 1 microM), transmural stimulation with pulse trains as described above always evoked relaxation but no membrane potential changes were observed. 10 It is concluded that nicotine and transmural stimulation can excite intramural noradrenergic nerves in guinea-pig trachea and thereby evoke relaxation. The membrane potential changes (slow wave suppression and hyperpolarization) are similar to those evoked by the administration of agonists at beta-adrenoceptors. Nicotine and transmural stimulation also excite non-adrenergic non-cholinergic inhibitory (NANCI) nerves. The relaxation evoked by the NANCI neurotransmitter is accompanied by little, if any, membrane potential change. PMID- 2884006 TI - Evidence that locus coeruleus is the site where clonidine and drugs acting at alpha 1- and alpha 2-adrenoceptors affect sleep and arousal mechanisms. AB - The behavioural and electrocortical (ECoG) effects of clonidine were studied after microinjection into the third cerebral ventricle, or microinfusion into some specific areas of the rat brain rich in noradrenaline-containing cell bodies (locus coeruleus) or into areas receiving noradrenergic terminals (dorsal hippocampus, amygdaloid complex, thalamus, frontal and sensimotor cortex). The ECoG effects were continuously analysed and quantified by means of a Berg-Fourier analyser as total power and as power in preselected bands of frequency. Clonidine (9.4 to 75 nmol) given into the third cerebral ventricle produced behavioural sedation and sleep and a dose-dependent increase in ECoG total voltage power as well as in the lower frequency bands. Much lower doses were required to produce similar behavioural and ECoG spectrum power effects after either unilateral or bilateral microinfusion of clonidine into the locus coeruleus. Doses of clonidine equimolar to those given into the third cerebral ventricle, were almost ineffective in inducing behavioural and ECoG sleep after their microinfusion into the dorsal hippocampus. In addition, a dose (0.56 nmol) of clonidine which, given into the locus coeruleus, produced marked behavioural sleep and ECoG synchronization, lacked effects when given into the ventral or anterior thalamus, into the amygdaloid complex or onto the frontal and sensimotor cortex. The behavioural and ECoG spectrum power effects of clonidine given into the third cerebral ventricle or into the locus coeruleus were prevented by antagonists of alpha 2-adrenoceptors but not by alpha 1-adrenoceptor antagonists. Intraventricular microinjection, or microinfusion into the locus coeruleus, of yohimbine, a selective alpha 2-adrenoceptor antagonist, produced behavioural arousal, increase in locomotor and exploratory activity, tachypnoea and ECoG desynchronization with a significant reduction in total voltage power. Similar stimulatory effects were also observed after microinjection of phentolamine into the same sites. No significant effects on behaviour and ECoG activity were evoked after intraventricular injection or microinfusion into the locus coeruleus of prazosin or methoxamine. PMID- 2884008 TI - Neuroleptic-induced hypothermia in mice: lack of evidence for a central mechanism. AB - The present study investigated the ability of neuroleptic drugs to induce hypothermia in mice when they were administered intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.). Twelve neuroleptics belonging to five chemical classes including phenothiazines, butyrophenones, benzamides, thioxanthenes and diphenylbutylpiperidines were injected i.p. All of them, except benzamides, induced a dose-dependent decrease in rectal temperature. Neuroleptics were administered i.c.v. via cannulae previously implanted in mice to determine whether this response might have a central origin. None of the drugs tested induced hypothermia at doses which did not produce toxic effects. These negative results suggest that neuroleptics act to elicit hypothermia via a peripheral, rather than a central mechanism. Since some neuroleptics possess alpha adrenolytic properties which could induce hypothermia by promoting vasodilatation, we attempted to antagonize the hypothermia produced by peripheral administration of two neuroleptics with phenylephrine, an alpha-adrenoceptor agonist that does not cross the blood-brain barrier. The hypothermia induced by both chlorpromazine and haloperidol was attenuated by phenylephrine, supporting the view that peripheral alpha-adrenoceptors may mediate neuroleptic-induced hypothermia. PMID- 2884010 TI - Acetylation, sulphasalazine and its effects. PMID- 2884009 TI - Alteration of thiol and superoxide dismutase status in rheumatoid arthritis treated with sulphasalazine. AB - Intracellular thiols (LSH), superoxide dismutase (SOD) and plasma thiols (PSH) are thought to have an important role in the protection of tissues from damage by oxygen-derived free radicals. The change in the levels of activity of these substances in patients with active rheumatoid arthritis treated with sulphasalazine for 6 months was assessed in 22 patients. Over this time there was a marked improvement in disease activity. This was accompanied by an early increase in red cell LSH and decrease in SOD, although by 6 months these changes had completely reversed. In addition the negative correlation between these indices at week 0 had disappeared by week 6. Over the 6 months there was a steady rise in PSH. The change in PSH is slow and is thus more likely to reflect a change in the disease process rather than an active role for the thiol, but the early changes in intracellular parameters may be of importance in the action of this drug. These changes are similar to changes found with other second-line drugs. It is also of interest that a drug which does not itself possess a thiol group is capable of altering the thiol status of cells. PMID- 2884011 TI - The regulation of cholecystokinin release from rat caudatoputamen in vitro. AB - Cholecystokinin (CCK) is one of the most abundant neuropeptides in the rat caudatoputamen (cp). CCK perikarya innervating cp are thought to originate in neurons in the claustrum/piriform cortex area of the amygdala. Previous studies on the release of CCK from cp have focused on the influence of dopamine agonists. The present study has examined the influence of other neuroactive substances on the release of CCK. The release of CCK from rat cp slices in vitro stimulated by potassium was quantitated with a specific CCK radioimmunoassay. This potassium stimulated release of CCK was Ca2+-dependent. Maximal stimulation of CCK release was observed at 55 mM potassium. Several lines of evidence indicate that the release of CCK from cp is inhibited by some other substance (or substances) released by a Ca2+-dependent mechanism from cp along with CCK. Release media from cerebral cortex or cp (called 'conditioned media' or CM) inhibits the release of CCK from fresh slices of cp but not from cerebral cortex. The release of dopamine from cp is unaffected by CM from cortex or cp. The identity of the substance in CM which inhibits CCK release from cp is still under investigation, though it appears not to be CCK, dopamine, acetylcholine, somatostatin, leucine enkephalin or gamma-aminobutyric acid. PMID- 2884012 TI - Neuroleptics decrease calcium-activated potassium conductance in hippocampal pyramidal cells. AB - Intracellular recordings were made from pyramidal CA1-neurones of the hippocampal slice preparation. Bath application of a wide variety of neuroleptics was found to depress the slow afterhyperpolarization, which is mediated in these neurons by a calcium-dependent potassium conductance occurring following a burst of spikes. The depression of this conductance took place in the presence of calcium spikes of normal amplitude and duration, and except in the case of trifluoperazine, without alteration in resting membrane potential or input resistance. PMID- 2884014 TI - Activation of periaqueductal grey pools of beta-endorphin by analgetic electrical stimulation in freely moving rats. AB - Electrical stimulation of the ventral midbrain periaqueductal grey (PAG) elicited an antinociception (analgesia) in freely moving rats. Stimulated animals displayed a pronounced decrease in levels of immunoreactive (ir)-beta-endorphin (beta-EP) in the midbrain PAG. This depletion was selective in that: animals placed in the chamber and not stimulated revealed neither an analgesia nor an alteration in levels of ir-beta-EP. No change in levels of ir-beta-EP was detectable in other brain regions. Both stimulated rats and rats placed in the chamber and not stimulated revealed a rise in circulating ir-beta-EP: the magnitude of this rise did not, however, differ between these groups. Levels of ir-Met-enkephalin, ir-Leu-enkephalin and ir-dynorphin A were modified neither in the PAG nor in other CNS tissues. The data demonstrate that electrical stimulation of the midbrain PAG selectively influences (presumably activates) pools of beta-EP therein. Together with our finding that destruction of PAG localized beta-EP neurones to block stimulation-analgesia, the data suggest that an activation of intrinsic pools of beta-EP underlies stimulation-produced analgesia elicited from the PAG in the rat. PMID- 2884013 TI - Cytoplasmic calcium elevation in hippocampal granule cell induced by perforant path stimulation and L-glutamate application. AB - Calcium-dependent fluorescence of a Ca2+ indicator (fura-2) loaded in the slice of guinea pig hippocampus was measured by a microscope/video-camera/photometry system. Tetanic stimulation of the perforant path (PP) or application of L glutamate caused increment of the fluorescence from the dendritic and somatic layers of the granule cells in the dentate gyrus. Magnitude of the increment depended on the frequency and intensity of the PP-stimulation or on the dose of L glutamate. 2-Aminophosphonovaleric acid, a glutamate-receptor antagonist, suppressed both PP-stimulus-induced and L-glutamate-evoked responses, while tetrodotoxin blocked the former only. Thus the fluorescence increment should represent an elevation of Ca2+ concentration in the postsynaptic cytoplasm of the granule cells. PMID- 2884015 TI - Long-term hyperalgesia induced by neonatal beta-endorphin and morphiceptin is blocked by neonatal Tyr-MIF-1. AB - Male rats were injected s.c. once daily during the first week of life with beta endorphin (BE), morphiceptin, the antiopiate Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), or one of the two opiate peptides in combination Tyr-MIF-1. Pups treated with neonatal BE removed their tails from a series of increasingly hot water baths significantly faster than controls on day 9, confirming our earlier studies. In addition, we found that Tyr-MIF-1 blocked this effect of BE. At 4.5 months, latency to lick a hindpaw in the hot-plate test was significantly faster in groups given BE alone, morphiceptin alone, or the control vehicle than in any of the 3 groups given Tyr-MIF-1. At 6 months the two groups given opiate peptides alone showed faster tail-flick latencies than the controls and the groups given Tyr-MIF-1. These results indicated that the long-term nociceptive changes induced by the opiate peptides were opposite to those induced by Tyr-MIF-1. Mean tail flick latencies of the groups on day 9 correlated well with hot-plate and tail flick scores in adulthood, indicating that the effects of the peptides were persistent. The neonatal peptide treatments did not differentially affect the analgesia induced by the stress of footshock or warm-water swim. Rats given either of the opiate peptides alone tended to fall off a rotorod faster than those in the other groups. These results support the role of Tyr-MIF-1 as an antiopiate and further illustrate the long-term effects of neonatally administered peptides. PMID- 2884017 TI - An aspect of the organizational principle of the gamma-aminobutyric acidergic system in the cerebral cortex. AB - The possibility of the colocalization of a Ca2+-binding protein, parvalbumin (PV), with peptides, cholecystokinin (CCK) and somatostatin (SS), all of which are known to be contained gamma-aminobutyric acidergic neurons in the cerebral cortex, was tested in the rat visual cortex by means of immunohistochemistry using the adjacent section technique. No PV immunoreactive (PV-I) neurons showed CCK-like immunoreactivity, and almost none (932 out of 934 PV-I neurons examined) showed SS-like immunoreactivity. These observations suggest that the GABAergic system of the cerebral cortex may consist of some distinct subsystems with different chemical and presumably physiological characteristics. PMID- 2884016 TI - Neurons in the paraventricular nucleus projecting to the median eminence: a study of their afferent connections from peripheral baroreceptors, and from the A1 catecholaminergic area in the ventrolateral medulla. AB - In male rats anesthetized with urethane-chloralose, extracellular recordings were made from tuberoinfundibular (TI) neurons in the paraventricular nucleus (PVN) identified by antidromic stimulation of the median eminence. Activation of baroreceptors induced by intravenous administration of phenylephrine inhibited approximately two-thirds of the 32 TI-neurons tested. Electrical stimulation of the A1-catecholaminergic area in the ventrolateral medulla produced an excitation in one half of the 28 neurons. Microinjection of L-glutamate (40 nl of 0.5 M solution of pH 7.4-7.6) to the same A1-area evoked an excitation in 7 out of 8 TI neurons tested. The results show that some TI-neurons in the PVN receive inhibitory synaptic inputs from the baroreceptors and excitatory inputs from neurons in the A1-catecholaminergic area. PMID- 2884018 TI - Increase in the stimulation-induced overflow of glutamate by fluoroacetate, a selective inhibitor of the glial tricarboxylic cycle. AB - Fluoroacetate is known to be taken up selectively by glia, where after forming fluorocitrate, it inhibits the tricarboxylic acid cycle. Since uptake into glia has a major role in the inactivation of synaptically released glutamate, the effect of fluoroacetate on the overflow of glutamate evoked by electrical field stimulation in slices of rat hippocampus was investigated. In agreement with previous reports, 1 mM fluoroacetate reduced the release and content of glutamine, but increased only slightly the overflow of glutamate induced by stimulation. If, however, 0.5 mM glutamine was added to the superfusion fluid, fluoroacetate nearly tripled the overflow of glutamate evoked by electrical field stimulation. The large glutamate overflow due to field stimulation in the presence of fluoroacetate was fully Ca2+ -dependent. Results confirm the major role of glia in the inactivation of glutamate. The absence of such an uptake may contribute to the in vivo convulsive effect of fluoroacetate. PMID- 2884019 TI - Immunohistochemical visualization of glutamate- and aspartate-containing nerve terminal pools in the rat limbic structures. AB - Antisera raised against glutamate or aspartate bound to bovine serum albumin were purified by affinity chromatography, and their specificities were verified by immunoblotting and by enzyme-linked immunosorbent assay. Immunohistochemical investigation using materials perfusion-fixed after long flushing demonstrated distinct laminar terminals with glutamate- or aspartate-like immunoreactivity throughout the limbic structures. This technique may offer a valuable tool for revealing the distribution of glutamatergic or aspartatergic nerve terminals. PMID- 2884020 TI - Effects of reduced magnesium on hippocampal synchrony. AB - Spontaneous, synchronous burst discharges originating in the CA2-CA3 region of guinea pig hippocampal slices occur when the concentration of magnesium in the perfusate is reduced below 250 microM. The burst frequency is greater than that seen with other convulsants and afterdischarge is common. Cyclic periods of bursting resembling ictal discharges occur spontaneously in some slices and with repetitive stimulation (0.5-2 Hz) in most slices. The spontaneous bursts are blocked by 2-APV suggesting the involvement of NMDA receptors in their generation. PMID- 2884022 TI - Is taurine a hypothalamic neurotransmitter?: A model of the differential uptake and compartmentalization of taurine by neuronal and glial cell particles from the rat hypothalamus. AB - Although taurine has been postulated to be a neurotransmitter or neuromodulator in the mammalian CNS, little is known concerning its role in brain function. Evidence suggesting that taurine may influence endocrine and homeostatic mechanisms via the hypothalamus resulted in our investigations into its function in this brain region. The main objectives of the research were to characterize the specific binding, uptake, and release of taurine in the hypothalamus. A specific aim was to examine the proposed neurotransmitter role for taurine in the hypothalamus. This was accomplished by comparing the characteristics and properties of the binding, uptake, and release of taurine with those for the classical neurotransmitters which satisfy the criteria for a neurotransmitter. On such a comparative basis, the characteristics of taurine uptake satisfy the neurotransmitter criterion of inactivation of taurine in the hypothalamus. However, the observed characteristics of taurine binding and release in the hypothalamus do not satisfy the respective neurotransmitter criteria of specific receptors and Ca2+-dependent evoked release. Therefore, solely on the basis of the experimental observations reported herein, we must conclude that taurine apparently does not function as a neurotransmitter in the hypothalamus. Two uptake systems were found in the P2 fraction, a high affinity uptake system and a low affinity uptake system. Uptake systems for taurine have previously been reported in glial and nerve cell homogenates, and therefore, because of the known contamination of crude synaptosomal preparations with glial particles, we sought to determine the cellular origin of the two taurine uptake systems in our crude preparation. Using a variety of diverse biochemical techniques such as hypo osmotic shock, release experiments and Arrhenius plots, we determined that physical changes of the media or depolarizing stimuli which would influence neuronal and glial cell particles differently, also had differing effects on high and low affinity taurine uptake or its release from the respective uptake compartments. We conclude that the high affinity taurine uptake system/compartment is located on/in neuronal membranes/particles/particles and that the low affinity taurine uptake system/compartment is located on/in neuronal membranes/particles and that model for the differential cellular transport and compartmentalization of taurine into neuronal and glial cells has important implications concerning its possible role in the CNS. PMID- 2884021 TI - In vivo or in vitro exposure to imipramine reduces alpha 2-adrenoceptor-mediated inhibition of cyclic AMP production in rat brain cerebral cortical slices. AB - The effect of in vivo or in vitro exposure to imipramine on alpha 2-adrenoceptor mediated inhibition of cAMP production in rat brain slices was examined. Chronic administration (10 mg/kg once daily for 14 or 21 days) of imipramine or in vitro exposure (100 microM, 60 min) to the antidepressant significantly reduced the ability of UK-14,304, an alpha 2-adrenoceptor agonist, to inhibit forskolin stimulated cAMP accumulation in cerebral cortical slices. This reduction was due to a decrease in the maximal response to the alpha 2-adrenergic agonist rather than to a decrease in its potency. Besides yielding a rapid and direct method for studying the effect of imipramine on brain receptors in vitro, these findings provide biochemical evidence in support of the notion that this drug, and perhaps other antidepressants, modifies alpha 2-adrenoceptor function in the central nervous system. PMID- 2884024 TI - [Effect of beta-adrenergic receptor blockers on the aggregation and secretory response of blood platelets]. PMID- 2884023 TI - Excitatory action of 5-HT on deglutitive substrates in the rat solitary complex. AB - The excitatory effect of serotonin (5-HT) on the pharyngeal stage of swallowing was investigated in urethane anaesthetised rats with respect to the involvement of neural substrates located in the central and intermediolateral regions of the nucleus tractus solitarii (NTS). Micropneumophoretic ejection of 5-HT 5-50 pmol either produced deglutitory responses or selectively facilitated the S-glutamate evoked pharyngeal responses when applied in 1-10 pmol prepulses. The excitatory/facilitatory effect of 5-HT was enhanced by intravenous threshold doses of the 5-HT-mimetic, quipazine (0.3-1 mumol/kg) and reversibly blocked by the 5-HT2-receptor antagonists, methysergide, metergoline and ketanserin. 5-HT doses exceeding 10-60 pmol gave rise to a non-selective reversible inhibition of glutamate- and acetylcholine (ACh)-evoked pharyngeal or oesophageal responses which was not prevented or reversed by 5-HT2-receptor antagonists, but was readily overcome by increasing the amount of glutamate or ACh ejected. Non selective deglutitive inhibition after high doses of 5-HT could, therefore, result from neuronal desensitization secondary to excessive stimulation or activation of a different type of 5-HT receptor. These results corroborate an excitatory role of 5-HT in both reflex and automatic swallowing and demonstrate that the NTS is a major site of serotoninergic facilitation of swallowing. PMID- 2884025 TI - [Occurrence of carcinoma in situ in postpubertal undescended testes]. PMID- 2884026 TI - Effect of transient neonatal hypothyroidism on the free aspartic acid, glutamic acid, and GABA content of different central auditory regions in the rat. AB - The aspartic acid, glutamic acid, and gamma-aminobutyric acid (GABA) contents were determined in four central auditory system regions in rats with transient neonatal hypothyroidism compared with control ones: the ventral and dorsal parts of the cochlear nucleus, the central nucleus of the inferior colliculus, the auditory cortex, and in an extra-auditory structure, the substantia nigra pars reticulata. The animals were sacrificed at 50 days of age, brain tissue samples were taken out by microdissection, and the free amino acids were extracted. The amino acid content was assessed by double-isotope labelling following two dimensional thin-layer chromatography separation. GABA content was significantly decreased in both cochlear nucleus regions and glutamic acid was elevated in the inferior colliculus. Neonatal hypothyroidism had no significant effect on the aspartic acid levels in the regions studied. The results suggest an effect of neonatal hypothyroidism on regional contents of free amino acids known as candidate neurotransmitters in the auditory system. PMID- 2884027 TI - Potentiation of the responses to transmural nerve stimulation by alpha-agonists: a possible role in vivo. AB - This study was undertaken to assess the effects of exogenous alpha-agonists on the effector response to transmural nerve stimulation in canine saphenous vein rings. The response to a fixed train (5 s duration) of transmural nerve stimulation (8 Hz, 0.3 ms, 9 V) applied every 5 min was determined in the control state and in the presence of subthreshold (for contraction) concentrations of noradrenaline, adrenaline, clonidine, and methoxamine. The maximum potentiations achieved by the three drugs were 246.2 +/- 36.9, 220.5 +/- 38.8, 384.3 +/- 78.7, and 353.3 +/- 68.0%, respectively. The potentiation observed was significantly inhibited by indomethacin (10(-6) mol/L) and propranolol (5 X 10(-6) mol/L). Both indomethacin and propranolol potentiated the response to transmural nerve stimulation. The potentiation of the responses to transmural nerve stimulation by alpha-agonists suggests that, presynaptic alpha 2-inhibition by circulating catecholamines is likely to be of limited biological significance in modulating the effector responses in the canine saphenous vein. PMID- 2884028 TI - Modulation of calcium by the carcinogenic process in the liver induced by a choline-deficient diet. AB - A diet devoid of choline and low in methionine (CD), without any added carcinogen, has been shown to induce 100% preneoplastic nodules and more than 50% cancer in the rat liver. Attempts to understand the mechanism by which a CD diet induces liver cell cancer revealed that like chemical carcinogens, a CD diet also appears to cause alterations in DNA, perhaps mediated by free radicals. Indeed, a CD diet induces nuclear lipid peroxidation prior to the changes in DNA. The CD diet induced DNA alterations coupled with continuing liver cell proliferation may account for the induction of initiated hepatocytes by the CD diet. To gain insight into the nature of free radicals generated by the CD diet, experiments were designed to determine whether agents that modulate free radical effects influence the CD diet induced changes in the liver. We investigated the effect of Ca2+ in the modulation of CD diet induced alterations in the liver. The results show that extra Ca2+ when added to the CD diet prevented some of the early changes due to choline deficiency, such as nuclear lipid peroxidation and DNA damage, but had little or no effect on the triglyceride accumulation in the liver. Also, the same CD diet with extra Ca2+, when used as a promoter after initiation by diethylnitrosamine, decreased the number and size of early putative preneoplastic foci and nodules. PMID- 2884029 TI - Transformation of a rat liver cell line: neoplastic phenotype and regulation of gamma glutamyl transpeptidase in tumour tissue. AB - A continuously dividing but non-transformed rat cell line was transformed by ras oncogenes and by aflatoxin. Transformed lines grew as solid tumours in nude mice with a short latency period. Different phenotypes were obtained from the transformed clones, and covered a wide spectrum of tumour types. While the commonest tumour type obtained was undifferentiated with unorganized spindle shaped and rounded cells, tumours with well formed trabeculae and adenomatous differentiation were also obtained. Gamma glutamyl transpeptidase (GGT), which showed an increase in transformed cells in tissue culture showed a variable expression in nude mouse tumours. While GGT positive cells were seen in all types of tumours they followed no consistent pattern and GGT negative areas were seen with a high frequency. However, in tumours showing adenomatous differentiation it was confined to the membrane on the luminal surface of the glandular structures. The different types of tumours resulting from the transformation of a single cell line provide a model of in vivo tumour development, supporting the possibility of a single stem cell origin of different types of liver neoplasms. This system also demonstrates the complexity of the regulation of GGT in tumour tissue. The influence of GGT on tumorigenesis has also been studied. PMID- 2884030 TI - Three industrial solvents investigated for tumor promoting activity in the rat liver. AB - Dioxane, perchloroethylene, and trichloroethylene were investigated as rat liver altered foci promoters in an initiation/promotion protocol. Animals were initiated with diethylnitrosamine, 30 mg/kg, injected i.p. 24 h after 2/3 partial hepatectomy. The chemical under study was administered by gavage once a day, 5 times a week for 7 weeks. Ten days after the last administration the animals were killed. Liver sections were stained for gamma-glutamyl-transpeptidase (GGT) and the number and total volume of GGT-positive foci was studied. Dioxane (1000 mg/kg) significantly increased the number and total volume of foci while a marginal effect was noted for the high dose of trichloroethylene (1100 mg/kg). A high dose of perchloroethylene (1100 mg/kg) had no effect. PMID- 2884031 TI - Characterization in vitro and in vivo of progressively adriamycin-resistant B16 BL6 mouse melanoma cells. AB - Adriamycin (ADR)-resistant sublines of B16-BL6 mouse melanoma selected by exposure to increasing concentrations of ADR were characterized in vitro for growth properties and in vivo for tumorigenicity and pulmonary metastases. The progressively resistant sublines adapted to grow in the presence of 0.025, 0.05, 0.1, and 0.25 microgram/ml ADR in monolayer culture were found to be 5-, 10-, 20 , and 40-fold ADR-resistant, respectively, compared to the parental sensitive cells, using a soft-agar colony assay and continuous ADR treatment for 7 days. The doubling time in monolayer culture of the parent sensitive and progressively ADR-resistant sublines of B16-BL6 melanoma cells was approximately 16-18 h. Although the colony-forming efficiency in soft agar of parental sensitive cells was only 0.5-4%, the 5-, 10-, 20-, and 40-fold ADR-resistant sublines had colony forming efficiencies of 15, 20, 30, and 77%, respectively. Tumorigenicity in C57BL/6 mice of progressively ADR-resistant sublines was similar to parental sensitive cells following s.c. and i.p. implantation of 10(5)-10(6) tumor cells. Experimental pulmonary metastases were significantly lower in ADR-resistant sublines with progressive resistance. Additionally, unlike the parental sensitive and 5-fold ADR-resistant B16-BL6 cells, the 10-, 20-, and 40-fold ADR-resistant sublines were spontaneously nonmetastatic. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunochemical detection of P-glycoprotein revealed the presence of a Mr 170,000 plasma membrane glycoprotein in the 40-fold ADR resistant subline and its counterpart maintained for 1 year in ADR-free medium. Results from this study suggest that progressively ADR-resistant B16-BL6 mouse melanoma cells selected in vitro demonstrate a marked increase in colony formation in soft agar and a decrease in the ability to produce pulmonary metastases, without alterations in tumorigenicity. PMID- 2884032 TI - New benzoic acid derivatives with retinoid activity: lack of direct correlation between biological activity and binding to cellular retinoic acid binding protein. AB - In this paper the biological activity of several newly synthesized benzoic acid derivatives of the Am- and Ch- series, which are structurally different from retinoic acid and arotinoids, was examined. These compounds inhibit squamous cell differentiation of rabbit tracheal epithelial cells in vitro as indicated by the inhibition of transglutaminase Type I and cholesterol 3-sulfate levels. In contrast to the inhibition of differentiation in rabbit tracheal cells, these compounds induce differentiation of mouse embryonal carcinoma F9 and human promyelocytic leukemia HL60 cells. The Am- and Ch- series of compounds also affect several parameters of cell proliferation. These agents are very potent inhibitors of growth of melanoma S91 cells and inhibit the induction of ornithine decarboxylase activity by phorbol 12-myristate 13-acetate in 3T6 fibroblasts. These results show that the Am- and Ch- derivatives elicit in several cell systems the same cellular responses as retinoic acid. We propose, therefore, that they exhibit mechanism(s) of action similar to those of retinoids. Comparison of the biological response with the binding capacity to the cellular retinoic acid binding protein shows a lack of a direct correlation. PMID- 2884033 TI - Isometric exercise: cardiovascular responses in normal and cardiac populations. AB - Isometric exercise produces a characteristic pressor increase in blood pressure which may be important in maintaining perfusion of muscle during sustained contraction. This response is mediated by combined central and peripheral afferent input to medullary cardiovascular centers. In normal individuals the increase in blood pressure is mediated by a rise in cardiac output with little or no change in systemic vascular resistance. However, the pressor response is also maintained during pharmacologic blockade or surgical denervation by increasing systemic vascular resistance. Left ventricular function is normally maintained or improves in normal subjects and cardiac patients with mild impairment of left ventricular contractility. Patients with poor left ventricular function may show deterioration during isometric exercise, although this pattern of response is difficult to predict from resting studies. Recent studies have shown that patients with uncomplicated myocardial infarction can perform submaximum isometric exercise such as carrying weights in the range of 30 to 50 lb without difficulty or adverse responses. In addition, many patients who show ischemic ST depression or angina during dynamic exercise may have a reduced ischemic response during isometric or combined isometric and dynamic exercise. Isometric exercises are frequently encountered in activities of daily living and many occupational tasks. Cardiac patients should be gradually exposed to submaximum isometric training in supervised cardiac rehabilitation programs. Specific job tasks that require isometric or combined isometric and dynamic activities may be evaluated by work simulation studies. This approach to cardiac rehabilitation may facilitate patients who wish to return to a job requiring frequent isometric muscle contraction. Finally, there is a need for additional research on the long term effects of isometric exercise training on left ventricular hypertrophy and performance. The vigorous training regimens currently utilized by international class and professional athletes should stimulate longitudinal studies of physiologic and pathophysiologic outcomes of intense isometric exercise training programs. PMID- 2884034 TI - Exercise prescription guidelines for normal and cardiac populations. AB - The basic components of aerobic exercise prescription include recommendations for optimal frequency, intensity, duration, mode, and progression of activity. The most effective program design involves the use of each of these components and incorporates specific coexistent medical problems and objective data derived from a multistage exercise tolerance test. In addition to the prescription of aerobic exercise, the use of circuit weight training and recreational activities has become accepted as an important part of a comprehensive exercise prescription. In effecting a well-designed and safe exercise program, the clinician must also be aware of environmental considerations and the effect of cardiac medications on the response to exercise. PMID- 2884035 TI - Exercise training in coronary artery disease. AB - Physical training using dynamic, nonisometric exercise can increase physical endurance and decrease cardiac work load of submaximal exertion. This is true for people with coronary artery disease and for normal individuals, and it may also be true for those with selected other cardiac diseases. Effective training should involve exercise at between 70 and 85 per cent of predicted maximal heart rate for 15 to 20 minutes or more at least three times a week. An exercise prescription should be written on the basis of individual patient needs and limitations and utilizing an exercise electrocardiogram test. Medically supervised exercise programs allow physical training for patients with heart disease to be conducted safely and efficiently. The effect of training in coronary disease patients is primarily attributable to increased efficiency of peripheral musculature and circulation; how much true cardiac adaptation results is variable. Training improves psychologic outlook, probably reduces selected risk factors for coronary disease, and may improve longevity. PMID- 2884036 TI - Immunocytochemical and ultrastructural evidence for a neurophysinergic innervation of the subcommissural organ of the snake Natrix maura. AB - The subcommissural organ (SCO) of the snake Natrix maura was studied by use of the immunoperoxidase procedure. Primary antisera against bovine neurophysins (Nps I + II, OXY-Np), oxytocin (OXY), mesotocin (MST), arginine-vasotocin (AVT), somatostatin (SOM), beta-endorphin (END) and bovine Reissner's fiber were used. A conventional ultrastructural study, with special emphasis on the nerve fibers present in the SCO, was also performed. Nerve fibers containing immunoreactive OXY-Np and MST were seen to reach the SCO. The staining of adjacent sections with the anti-Reissner's fiber serum showed that the OXY-Np- and MST-immunoreactive fibers were distributed among the cell bodies and processes of the ependymal secretory cells. No fibers containing immunoreactive OXY, AVT, SOM or END were found in the SCO. The ultrastructural analysis revealed in the SCO the presence of nerve fibers filled with electron-dense granules, 170-210 nm in diameter. Although a direct apposition between these fibers and the SCO cells was frequently seen, no synaptic differentiations were identified. Structures identical to the Herring bodies (found in the neurohypophysis) were seen in the SCO. PMID- 2884037 TI - Genetic linkage of von Recklinghausen neurofibromatosis to the nerve growth factor receptor gene. AB - von Recklinghausen neurofibromatosis (VRNF) is one of the most common inherited disorders affecting the human nervous system. VRNF is transmitted as an autosomal dominant defect with high penetrance but variable expressivity. The disorder is characterized clinically by hyperpigmented patches of skin (cafe au lait macules, axillary freckles) and by multiple tumors of peripheral nerve, spinal nerve roots, and brain (neurofibromas, optic gliomas). These tumors can cause disfigurement, paralysis, blindness, and death. We have determined the chromosomal location of the VRNF gene by genetic linkage analysis using DNA markers. The VRNF gene is genetically linked to the locus encoding nerve growth factor receptor, located on the long arm of chromosome 17 in the region 17q12--- 17q22. However, crossovers with the VRNF locus suggest that a mutation in the nerve growth factor receptor gene itself is unlikely to be the fundamental defect responsible for the VRNF phenotype. PMID- 2884038 TI - An abnormal terminal X-Y interchange accounts for most but not all cases of human XX maleness. AB - To determine if human XX maleness results from an abnormal chromosomal X-Y interchange, we studied the inheritance of the paternal pseudoautosomal region in nine patients. Those six patients in whom Y-specific DNA was found (Y(+)) inherited the entire pseudoautosomal region from the paternal Y chromosome and lost that of the paternal X chromosome. Moreover, in three Y(+) cases, we observed the deletion of a paternal Xp locus tightly linked to the pseudoautosomal region. These results definitively show that an abnormal and terminal X-Y interchange during paternal meiosis causes Y(+)XX maleness. In contrast, no abnormal X-Y interchange was observed in any of the three Y(-) cases analyzed, suggesting that maleness can occur in the absence of any Y-specific DNA. PMID- 2884039 TI - A histidine-rich protein gene marks a linkage group favored strongly in a genetic cross of Plasmodium falciparum. AB - Two histidine-rich protein genes in Plasmodium falciparum are related by an ancestral duplication and interchromosomal transposition. We have followed the inheritance of these genes in a cross between two clones of P. falciparum. Examination of progeny shows that one gene, encoding the protein HRP-II, behaves as expected and may be inherited from either parent. The other gene, encoding HRP III, has been found to derive from one parent in all progeny examined. We conclude the linkage group marked by HRP-III is favored strongly in the cross. This linkage group spans a region at one end of chromosome 13. Growth studies suggest the favored inheritance is explained by rapid expansion of progeny possessing the HRP-III marker relative to slower growth of progeny without it. PMID- 2884040 TI - Expression of the v-erbA oncogene in chicken embryo fibroblasts stimulates their proliferation in vitro and enhances tumor growth in vivo. AB - In contrast to uninfected chicken embryo fibroblasts (CEFs), CEFs infected with a retroviral vector that carries the v-erbA gene of avian erythroblastosis virus displayed new properties. These included limited anchorage-independent growth in soft agar, growth without latency in serum-supplemented medium, ability to overcome quiescence induced by serum deprivation, growth at low cell density, and an extended life span in vitro. Furthermore, when explanted in vivo onto the chorioallantoic membrane of chicken embryo, the transformed CEFs expressing v erbA in addition to v-erbB exhibited a high proliferative rate, giving rise to fibrosarcoma tumors that were ten times larger than those developed from transformed CEFs expressing v-erbB alone. All these data show that CEFs expressing the v-erbA oncogene display activated growth and suggest that the v erbA product interferes with the mechanisms regulating the growth and/or differentiation of primary CEFs. PMID- 2884041 TI - PrP and the nature of the scrapie agent. PMID- 2884043 TI - Germinal vesicle migration and dissolution in Rana pipiens oocytes: effect of steroids and microtubule poisons. AB - Germinal vesicle migration (GVM) as evidenced by the appearance of the germinal vesicle at the animal pole surface was induced by nocadazole and demecolcine (colcemid). Nocodazole significantly lowered the progesterone ED50 for germinal vesicle dissolution (GVD). Both demecolcine and nocodazole enhanced centrifugation-induced GVM (i.e., lowered ooplasmic viscoelasticity) after 6-h incubation, and both potentiated the effect of progesterone in this assay. Estradiol, by contrast, inhibited GVM induced by demecolcine in both follicle enclosed and denuded oocytes. Estradiol was also found to inhibit the normal enhancement of centrifugation-induced GVM by demecolcine or progesterone. Taxol was found to have effects that were generally opposite to those of demecolcine and nocodazole. Taxol inhibited centrifugation-induced GVM either alone or in the presence of progesterone. In addition, taxol significantly increased the progesterone ED50 for GVD induction. Taken together the available data support the hypothesis that microtubules play a role in maintaining the internal position of the germinal vesicle in the prematuration oocyte and that changes occur in the oocyte cytoskeleton during maturation. PMID- 2884042 TI - Mitochondrial protein import: nucleoside triphosphates are involved in conferring import-competence to precursors. AB - The role of nucleoside triphosphates (NTPs) in mitochondrial protein import was investigated with the precursors of N. crassa ADP/ATP carrier, F1-ATPase subunit beta, F0-ATPase subunit 9, and fusion proteins between subunit 9 and mouse dihydrofolate reductase. NTPs were necessary for the initial interaction of precursors with the mitochondria and for the completion of translocation of precursors from the mitochondrial surface into the mitochondria. Higher levels of NTPs were required for the latter reactions as compared with the early stages of import. Import of precursors having identical presequences but different mature protein parts required different levels of NTPs. The sensitivity of precursors in reticulocyte lysate to proteases was decreased by removal of NTPs and increased by their readdition. We suggest that the hydrolysis of NTPs is involved in modulating the folding state of precursors in the cytosol, thereby conferring import competence. PMID- 2884044 TI - Differential expression of surface markers on thymic lymphomas induced by two carcinogenic agents in different mouse strains. AB - Expression of several thymocyte surface antigens was monitored in a murine model system of thymic lymphoma induction in two different strains of mice. RF/J mice are sensitive to tumor induction by N-nitrosomethylurea (NMU) and by gamma irradiation, while 129/J mice form tumors only upon NMU treatment. Latency periods for tumor formation were characteristically different depending upon the inducing agent and the mouse strain. We observed differences in thymic leukemia antigen and H-2K expression according to the mode of tumor induction and in relation to the mouse strain, implying multiple factors involved in target cell selection and tumor progression. PMID- 2884045 TI - A Thy-1.1-specific monoclonal alloantibody activates both mouse and rat T cells. AB - In an attempt to further evaluate the role of Thy-1 in the antigen-independent triggering of mouse T cells, we have examined the activating properties of two Thy-1.1-specific mouse monoclonal antibodies (mAb). These reagents were established from an (A.TH X A.TL)F1 hybrid mouse (Thy-1b) immunized with IL-2 producing (BALB/c (Thy-1b) X BW5147 (Thy-1a)) T hybridoma cells. Although both mAb recognized the same Thy-1.1 determinant, one mAb of the gamma 3,kappa class (H171-146) was found to induce several T hybridoma cells to produce IL-2, and AKR thymocytes or cloned helper T cells to proliferate, whereas another mAb of the gamma 1,kappa class (H171-112) failed to do so even in the presence of phorbol myristic acetate (PMA). Increased IL-2 responses of T hybridoma cells were observed when the cell bound Thy-1.1-specific mAb were crosslinked by goat anti mouse Ig (GaMIg) antibodies. Both a T-cell activating rat anti-Thy-1.2 mAb and the anti-Thy-1.1 mAb H171-146, although directed at distinct cell surface molecules, synergistically stimulated IL-2 production by T hybridoma cells. In addition, the mouse mAb H171-146 was found to stimulate LOU/M rat thymocytes to proliferate in the presence of exogenous IL-2. These data demonstrate that T cells can use Thy-1 as a signal-transducing molecule in both mouse and rat species, and support the notion that the activating properties of Thy-1.1 specific mAb are influenced by their heavy chain isotypes. PMID- 2884046 TI - Endogenous opioids in spinal cord injury: a critical evaluation. AB - Based upon evidence that opioid antagonists improve neurological outcome following either traumatic or ischemic spinal cord injury, endogenous opioids have been implicated in the pathophysiology of these disorders. Naloxone improved both spinal cord perfusion and neurological function following traumatic spinal cord injury in cats, and was subsequently observed to improve neurological outcome following ischemic spinal cord injury in rabbits. Using several opioid antagonists with varied selectivities for different types of opioid receptors, it was suggested that kappa opioid receptors are involved in both these models of spinal cord injury. In addition, spinal cord trauma in rats is associated with increased concentrations of the endogenous kappa agonist dynorphin A, and increased kappa opioid receptor binding capacity localized to the injury site. Furthermore, dynorphin A induces hindlimb and tail flaccidity following intrathecal injection in rats. Thus, the pathophysiological effects of endogenous opioids in spinal cord injury have been proposed to involve dynorphin A interactions with kappa opioid receptors. However, disparities between the actions of intrathecally injected dynorphin A in rats and the presumed actions of endogenous dynorphin A in cat and rabbit spinal cord injury have been revealed in recent experiments. Paralysis resulting from intrathecal dynorphin A is not altered by opioid receptor antagonists or TRH, produced by non-opioid dynorphin A fragments but not by other selective kappa opioid agonists, and associated with non-opioid mediated reductions in spinal cord blood flow. Furthermore, despite reports of endogenous opioid changes following rat spinal cord trauma, in contrast to cats and rabbits, naloxone failed to improve neurological outcome following traumatic rat spinal cord injury. Thus, the specific endogenous opioids and opioid receptor types involved in spinal cord injury remain to be resolved, and do not appear to be universal among different models of spinal cord injury in different species. Additionally, dynorphin A may participate in spinal cord injury mechanisms in the rat through non-opioid actions. PMID- 2884048 TI - Obstetrical anaesthesia at Winnipeg Women's Hospital 1975-83: anaesthetic techniques and complications. AB - The obstetrical anaesthesia experience of the Winnipeg Women's Hospital from 1975 to 1983 was reviewed (n = 22,925 infants). Use of narcotics in labour for analgesia decreased from 38.7 to 18.3 per cent of the deliveries. For analgesia during spontaneous vaginal deliveries, epidural anaesthesia increased from 6.0 to 24.0 per cent, inhalational analgesia decreased from 53.7 to 3.2 per cent while "no anaesthetic intervention" rose from 40.3 to 72.8 per cent. Use of epidural anaesthesia for Caesarean section increased from 58.7 to 82.6 per cent. The most common acute complications of anaesthesia were hypotension and inadvertent dural puncture during epidural catheterization. The incidence of hypotension decreased from 28.3 to 17.4 per cent during the nine-year period. Dural puncture decreased from 4.7 to 1.1 per cent of all epidural administrations. Postpartum complaints (that were thought to be related to anaesthesia) were mainly headache, back pain and sore throat. The incidence of these complaints also decreased over the study period. PMID- 2884050 TI - Ethoxyquin alone induces preneoplastic changes in rat kidney whilst preventing induction of such lesions in liver by aflatoxin B1. AB - Pretreatment of Fischer 344 rats with the antioxidant ethoxyquin (EQ), followed by administration of aflatoxin B1 (AFB1) in the continuing presence of EQ was used to examine the effect of the antioxidant on liver and kidney. EQ (0.5% in diet) completely prevented the formation of AFB1-induced preneoplastic liver lesions as judged by morphological alteration, or by markers such as gamma glutamyl transpeptidase, glutathione S-transferase P or J1, an unknown membrane bound antigen. While protection was afforded to the liver, EQ alone caused severe damage to the kidney. Many changes were those of chronic glomerulonephrosis, such that EQ appeared to accelerate the ageing process. In addition, many hyperplastic and putative preneoplastic tubules were visible, suggesting that EQ may be exerting a carcinogenic effect in the kidney. PMID- 2884049 TI - Variations of ornithine decarboxylase activity and S-adenosyl-L-methionine and 5' methylthioadenosine contents during the development of diethylnitrosamine-induced liver hyperplastic nodules and hepatocellular carcinoma. AB - Liver ornithine decarboxylase (ODC) activity and content of S-adenosyl-L methionine (SAM) and its catabolite 5'-methylthioadenosine (5'-MTA) were determined in the late stages of hepatocarcinogenesis. Wistar rats received one diethylnitrosamine dose, followed by a partial hepatectomy at the midpoint of a 15-day treatment with 2-acetylaminofluorene (2-AAF), and then by an 18-week phenobarbital (PB) treatment. Thirty-eight per cent of liver was gamma glutamyltranspeptidase (GGT)-positive and no visible nodules and hepatocellular carcinomas developed 16 weeks after starting 2-AAF feeding. Hyperplastic nodules and hepatocellular carcinomas were found on weeks 24 and 56 respectively. On weeks 24 and 56 only approximately 10% of liver was occupied by GGT-positive foci. At all times studied the foci exhibited a low labeling index (LI), and liver ODC activity was near control values. By contrast, a high ODC activity and LI and a low SAM and 5'-MTA levels were found in hyperplastic nodules and neoplasia. These tissues exhibited a high 5'-MTA phosphorylase activity. SAM administration during PB treatment, caused a 25-36% fall of GGT-positive liver and prevented the development of hyperplastic nodules and hepatocellular carcinomas. This was coupled to a sharp increase of SAM and 5'-MTA liver contents. SAM and 5'-MTA inhibited hepatocyte DNA synthesis in vitro. The addition of 5'-MTA to the reaction mixture for the ODC assay strongly inhibited ODC activity. However, the preincubation of SAM with liver homogenates or hepatocytes, used to prepare crude ODC, was necessary to inhibit ODC activity by SAM. Adenine, an inhibitor of 5'-MTA-phosphorylase, enhanced inhibition of DNA synthesis and ODC activity by SAM and 5'-MTA. Thus, during a prolonged promoting treatment a selected population of GGT-positive foci appears to acquire a stable phenotype characterized by a high DNA and polyamine synthesis. The development of nodules and carcinomas is associated with low SAM and 5'-MTA contents and high ODC activity and LI. 5'-MTA accumulation, during SAM administration, is probably responsible for the inhibition of promotion by SAM. PMID- 2884051 TI - Induction of gamma-glutamyl transpeptidase mRNA by aflatoxin B1 and ethoxyquin in rat liver. AB - We have studied the induction of rat liver gamma-glutamyl transpeptidase (GGT) mRNA by the antioxidant ethoxyquin and during aflatoxin B1-induced carcinogenesis. Using a rat kidney GGT cDNA probe, Northern blot analysis revealed that GGT mRNA induced in liver by either compounds was slightly larger than that found in untreated kidney. GGT mRNA was not detected in untreated liver or freshly isolated hepatocytes, but induction of the message in treated tissues correlated with the increase in enzymic activity observed by histochemistry and quantitative assay. Slot-blot analysis of poly(A)+ mRNA indicated that constitutive GGT mRNA levels in kidney were at least 5-fold greater than those in the most GGT-positive liver-derived tissue examined. PMID- 2884052 TI - Experimental conditions influence [3H]-dihydroalprenolol binding characteristics to living HeLa cells due to morphological changes: a warning. AB - Harvesting of plated growing HeLa cells, followed by incubation of these cells without any addition at 37 degrees C was found to cause changes in the cell shape. This phenomenon is accompanied by a diminished binding of the beta adrenergic antagonist [3H]-dihydroalprenolol and the alpha-adrenergic antagonist phentolamine to a binding compartment not representing beta-adrenergic receptors. These binding sites have a high affinity for hydrophobic agents and most probably represent lipophilic structures in the cellular membrane. Changes in the cell shape obviously cause alterations in the physical properties of the plasma membrane. This might lead to misinterpretations of the results from experiments in which the redistribution of beta-adrenergic receptors is followed during incubation with agonists, as receptor occupation with subsequent receptor redistribution is possibly accompanied by effects on the membrane microviscosity. It is concluded that investigations performed in order to follow physiological events like receptor redistribution and desensitization processes, may be obfuscated by changes in the normal physical state of the living cells. PMID- 2884053 TI - Cardiovascular problems in pregnancy. PMID- 2884047 TI - Anaesthetic premedication: aims, assessment and methods. PMID- 2884054 TI - The mode of action of anti-allergic drugs. PMID- 2884055 TI - Dynorphin(1-8) immunoreactivity in brainstem and hypothalamic nuclei of normotensive and age-matched hypertensive rat strains. AB - The concentration of dynorphin (1-8) immunoreactivity [ir-dyn(1-8)] was measured in 10 hypothalamic and 11 brainstem nuclei of Sprague-Dawley (SD) and 6- and 14 week old Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats. The highest concentrations of ir-dyn(1-8) were found in the lateral preoptic and lateral hypothalamic areas of the hypothalamus and the solitary tract nucleus of the brainstem. Levels of the peptide were low in other brainstem nuclei compared to hypothalamic areas. There was a significant reduction in ir-dyn(1-8) concentrations at 14 weeks of age compared to 6 weeks of age in all 9 nuclei examined in SH and WKY rats. However, there were no differences between the strains at either age. These changes may be related to the increase in blood pressure that occurs in both SH and WKY rats over this age range although other factors must also be involved to produce the higher blood pressure levels of the SH rat. PMID- 2884056 TI - Pharmacological therapy of portal hypertension. PMID- 2884057 TI - Excessive helper T-cell function in patients with idiopathic pulmonary fibrosis: correlation with disease activity. AB - Peripheral blood T lymphocytes from patients with idiopathic pulmonary fibrosis and matched normal controls were examined for their helper function in an in vitro antibody synthesis assay. This assay measures the dose-related T-cell regulation of antibody production by B cells in the presence of pokeweed mitogen. Eight patients of 14 expressed significantly increased helper T-cell activity, three exhibited no change, and three had depressed helper T-cell function. All of the patients with excessive helper T-cell function had an active neutrophilic alveolitis as determined by bronchoalveolar lavage on the day of study. Five of the 14 patients studied were determined to have a low percentage of neutrophils (less than 10%) in their BAL fluid. None of these were found to express excessive helper T-cell function; in fact three of the five had depressed helper T-cell function. No correlation between steroid therapy or smoking history and the expression of excessive helper function was observed. None of the peripheral blood T-cells from IPF patients were actively producing IL-2 in vitro without further stimulation, providing evidence against constitutive production in vivo. T cells were also examined for their ability to produce lymphokines promoting fibroblast proliferation. Enhanced stimulation of fibroblast proliferation was shown to positively correlate with disease activity as determined by the degree of neutrophilic alveolitis (r = 0.68). The significant correlation between neutrophilic alveolitis and excessive helper T-cell function observed here suggests that altered systemic immunoregulation accompanies local inflammation. The further participation of patient T cells in promoting fibroblast proliferation may contribute to the development of fibrosis, or to the contrary may be an attempt to limit the fibrotic process. PMID- 2884058 TI - Pharmacologic effects on labor: effects of drugs on dystocia, labor, and uterine activity. PMID- 2884059 TI - A single dose of three different ophthalmic beta-blockers antagonizes the chronotropic effect of isoproterenol in healthy volunteers. AB - The systemic effect of three beta-blocking eyedrops was compared in a placebo controlled, double-blind trial in 12 healthy male volunteers. Each subject received successively each treatment in random order at weekly intervals. The eyedrops administered were as follows: 0.5% timolol, 2% carteolol, 0.6% metipranolol, and placebo. We evaluated the intraocular pressure and systemic beta-blockade 3 hours after a single administration of one eyedrop in each eye. The systemic beta-blocking effect was evaluated by the isoproterenol sensitivity test, that is the dose of isoproterenol required to increase resting heart rate by 25 bpm (I25). Each beta-blocking eyedrop antagonized the chronotropic effect of isoproterenol. I25 for placebo was 3.1 +/- 0.5 micrograms, for metipranolol 5.2 +/- 0.9 micrograms (P less than 0.005), for timolol 10.9 +/- 1.9 micrograms (P less than 0.001), and for carteolol 39.6 +/- 5.4 micrograms (P less than 0.0005). Each treatment significantly decreased the intraocular pressure: metipranolol 3.6 +/- 0.4 mm Hg (P less than 0.001), timolol 2.44 +/- 0.4 mm Hg (P less than 0.01), and carteolol 2.38 +/- 0.48 mm Hg (P less than 0.01) compared with placebo. The resting heart rate and blood pressure were not influenced by the treatments. Even though the results might be different in the case of an earlier or a later time of evaluation or chronic administration, we believe that the isoproterenol sensitivity test may be used to evaluate the systemic effect of beta-blocking eyedrops. PMID- 2884060 TI - Pancreatic islet amyloid and elevated proinsulin secretion in familial maturity onset diabetes. AB - Quantitative morphometry of immunostained pancreatic islet cells in a surgical specimen from a maturity-onset diabetic (MOD) patient (A) has been combined with a study of beta-cell secretion in him and his MOD son (B). The morphometry showed intra-islet amyloid deposits in 24% of islet sections which is a similar distribution to that found in 7 other MODs, (median 24%, range 0-95%). The distribution of islet cells in the pancreas from A was similar to the 7 MODs and 9 age matched non-diabetic subjects (mean beta-cell area per exocrine area, A, 2%; MODs, 1.45%; controls 1.8%). There was a significantly smaller percentage beta-cell area per islet area in A and the other MODs compared to the controls. Beta-cell secretion was studied by an intravenous glucose infusion, 5 mg/kg ideal body wt. min-1 in A and B and 4 other MODs on sulphonylurea or diet therapy. Fasting plasma glucose was high in both A and B (16 and 7.6 mmol/l respectively) in spite of sulphonylurea therapy. Similarly, A and B had elevated fasting plasma levels of insulin, (0.055 and 0.13 pmol/ml respectively) and C-peptide (0.573 and 1.39 pmol/ml respectively). Plasma proinsulin formed a higher percentage of the immunoreactive insulin in fasting plasma samples of both A (36%) and B (43%) than in less hyperglycaemic MODs on diet alone (26%) or sulphonylurea therapy (17%) and the glucose stimulated proinsulin content was even higher (A, 50%; B, 53%; MODs, diet, 19%; sulphonylureas, 16%). Elevated proinsulin levels in a patient with islet-amyloid is consistent with the hypothesis that amyloid may be derived from abnormal beta-cell secretion. PMID- 2884061 TI - Rapid identification of enterococci by pyrrolidonyl aminopeptidase activity (PYRase). AB - Group A streptococci and enterococci can be differentiated from other streptococci by their ability to cleave pyrrolidonyl beta-naphthylamide (PYRase). We evaluated two PYRase systems [Strep-A-Chek (SAC), E-Y Laboratories, San Mateo, CA; Strep-A-Fluor (SAF), BioSpec, Inc., Dublin, CA) for the presumptive identification of enterococci. Initially, 40 enterococcal and 21 nonenterococcal streptococci were tested, retrospectively. A prospective comparison of SAC and SAF to bile-esculin reaction (BE) was then incorporated into our routine procedure for the identification of non-beta-hemolytic streptococcal colonies from cultures. All isolates were speciated using standard biochemical tests. We encountered 85 enterococcal and 26 nonenterococcal isolates. Tests were performed on colonies from primary plates whenever possible (77 isolates). Sensitivity and specificity of both SAC and SAF were greater than 96% in identifying enterococci from routine cultures. These PYRase tests were cost-effective, easily adaptable to work-flow, and yielded results within 30 min. Thus, PYRase testing appears to be a reasonable alternative for the identification of enterococci in the clinical laboratory. PMID- 2884063 TI - Carrier detection and gene analysis of Duchenne muscular dystrophy. PMID- 2884062 TI - Highly polymorphic RFLP probes as diagnostic tools. PMID- 2884064 TI - Molecular genetics of Huntington's disease. AB - The discovery of a DNA marker linked to the HD gene has provided new avenues into the investigation of this devastating disorder. Genetic investigations have determined that in most and possibly all HD families, the disease is caused by a defect that maps near the telomere on the short arm of chromosome 4. DNA markers will soon provide presymptomatic diagnosis for this disorder, but this increased capability may be a mixed blessing in the absence of effective treatment. The most hopeful route to developing such treatment lies in cloning and characterization of the primary defect. Precise genetic and physical mapping using DNA markers and improvements in techniques for analyzing large segments of DNA have set the stage for cloning of the disease gene in the near future. It will undoubtedly reveal an interesting mechanism for complete phenotypic dominance in man for comparison with completely dominant mutations in other species, particularly Drosophila. The nature of the defect may provide new insights into the functional organization of the central nervous system. For the sake of the many individuals who are afflicted by HD or who are asymptomatic gene carriers, it is to be hoped that cloning and characterizing the disease gene will also yield the necessary information to develop an effective therapy. PMID- 2884065 TI - Molecular basis of phenylketonuria and potential somatic gene therapy. PMID- 2884066 TI - Molecular genetics of apolipoproteins and coronary heart disease. AB - A variety of DNA markers for apolipoprotein genes were examined among patients with angiocardiographically proven heart disease and among a variety of normal individuals with various lipid values. An increased frequency of an apoAI-CIII SstI RFLP and an apoB minisatellite (allele 5) was found among patients with CHD. Higher levels of cholesterol were found among carriers of the rare apoB TaqI and the common apoCII TaqI variants, whereas higher levels of triglycerides were found in carriers of the common apoAII MspI and the rare apoB XbaI variants. Lower levels of HDL were found among carriers of the common apoAII MspI and the rare apoB PvuII variants. The biological significance of these results and those of other investigators for the pathogenesis of CHD and hyperlipidemia is suggestive but not yet fully clarified. Additional genetic epidemiologic studies and family investigations will be required. Currently used statistical methodology may lead to false inferences regarding the genetic equilibrium or disequilibrium status of closely linked DNA variants. Conclusions regarding the presence of genetic equilibrium if closely linked flanking markers are in disequilibrium may be faulty. PMID- 2884067 TI - DNA markers and genetic variation in the human species. PMID- 2884068 TI - Mapping complex genetic traits in humans: new methods using a complete RFLP linkage map. PMID- 2884069 TI - The primate alpha-globin gene family: a paradigm of the fluid genome. PMID- 2884070 TI - Molecular biology of the class II region of the human major histocompatibility complex. PMID- 2884071 TI - HLA class II RFLPs are haplotype-specific. PMID- 2884072 TI - The human interleukin-2 receptor: role in normal T-cell growth and association with HTLV-I-induced T-cell leukemia. PMID- 2884073 TI - HLA-DQ and T-cell receptor genes in insulin-dependent diabetes mellitus. PMID- 2884074 TI - Mental disorders in the elderly. PMID- 2884076 TI - Errata: Trauma to the ankle and foot. PMID- 2884075 TI - Glutamine synthetase in liver of the American alligator, Alligator mississippiensis. AB - Glutamine synthetase was shown to be localized in liver mitochondria of the American alligator, Alligator mississippiensis, by immunofluorescent staining of frozen liver sections and by the detection of enzymatic activity and immunoreactive protein in the mitochondrial fraction following subcellular fractionation of liver tissue by differential centrifugation. The primary translation product of alligator liver glutamine synthetase mRNA was shown to have an Mr = 45,000 which is similar if not identical in size to that of the mature subunit. This mRNA was found to be heterogeneous in size with a major form corresponding to 2.8-3.0 kb and a lesser form corresponding to around 2 kb. Both are in excess of the size required to code for the glutamine synthetase subunit. The synthesis and presumably the mitochondrial import of glutamine synthetase in alligator liver are thus very similar to the same processes in avian liver. Despite the excretion of a high percentage of nitrogen as ammonia, the demonstration of a mitochondrial glutamine synthetase indicates the alligator has the typical avian-type uricotelic ammonia-detoxification system in liver. This suggests that the transition to uricotelism occurred in the sauropsid line of evolution and has persisted through both the lepidosaurian (snakes, lizards) and archosaurian (dinosaurs, crocodilians, birds) lines. PMID- 2884077 TI - Interaction between alpha 2- and beta 2-adrenergic receptors in rabbit ciliary processes. AB - The interaction between the alpha 2- and beta 2-adrenergic receptors of ciliary processes has been studied by examining dose-response curves for adrenergic agonist stimulation of cyclic AMP production by intact, excised rabbit ciliary processes. Stimulation of cyclic AMP production by 1-isoproterenol is maximum from 0.1 to 1.0 microM; at higher concentrations stimulation decreases and approaches basal levels. Decreased cyclic AMP production at high concentrations of isoproterenol is blocked by the specific alpha 2-adrenergic antagonist, yohimbine, but not by the alpha 1-adrenergic antagonist, prazosin. Ciliary processes from animals after bilateral cervical ganglionectomy also show reduced cyclic AMP production at high concentrations of isoproterenol and this reduction is blocked by yohimbine, but not prazosin. This experiment suggests that the inhibition at high concentrations of isoproterenol is mediated by postsynaptic alpha 2-adrenergic receptors. Cyclic AMP production is relatively insensitive to epinephrine and norepinephrine, but their responses are potentiated by yohimbine. Catecholamines and clonidine, a specific alpha 2-adrenergic agonist, exhibit dose dependent inhibition of forskolin-stimulated cyclic AMP production by ciliary processes. I50s from the dose-response curves are consistent with the characteristic binding affinities of these adrenergic agonists for alpha 2 adrenergic receptors: clonidine = epinephrine greater than norepinephrine greater than isoproterenol. Inhibition of forskolin-stimulated cyclic AMP production by clonidine is blocked by yohimbine but not by prazosin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884078 TI - Visualization of endocytotic pits in capillary endothelia of dog heart by scanning electron microscopy. AB - Endocytotic transport may provide a mechanism for myocyte uptake of agents which ameliorate the effects of myocardial ischaemia. Examination of the inner capillary surface by transmission electron microscopy (TEM) is tedious and slow, while use of scanning electron microscopy permits the examination of greater areas in less time. Methods to obtain oblique exposures of capillaries and provide sufficient resolution to observe endocytotic pits were explored. Partial success was achieved using glutaraldehyde fixed tissue, treated with 30% glycerol, frozen-fractured under hexane at -85 degrees C, then dehydrated with acetone at -25 degrees C, critical-point dried and lightly coated with gold. Ultrastructural detail comparable with TEM images of heart tissue was obtained, but the resolution appeared limited by the coating process. It was not possible to verify stimulation of endocytosis by AMP in coronary capillary endothelia with scanning electron microscopy, due to this limitation. PMID- 2884079 TI - A new human RFLP identified by 7D2 places D13S10 proximal to esterase D. PMID- 2884080 TI - The radioreceptor assay for TBII in the spectrum of thyroid stimulating immunoglobulins. PMID- 2884081 TI - The inhibitory effect of azelastine and ketotifen on histamine-induced bronchoconstriction in asthmatic patients. AB - We studied the antihistaminic property of a new compound, azelastine, on histamine-induced bronchoconstriction and compared it with ketotifen and placebo. In 12 patients with bronchial asthma we performed histamine bronchial challenges before and four hours after ingestion of placebo, 2.0 mg ketotifen, and 4.4 mg azelastine given in a double-blind, randomized, cross-over fashion. Ketotifen and azelastine provided significant protection compared with placebo. No statistically significant difference between ketotifen and azelastine could be detected. As the antihistaminic effect of azelastine does not predict the therapeutic usefulness in the maintenance therapy of bronchial asthma, further studies are indicated. PMID- 2884082 TI - Mast cell mediators and asthma. AB - Mast cells are found beneath the basement membranes, near blood vessels in the submucosa, adjacent to submucous glands, scattered throughout the muscle bundles, in the interalveolar septa and in the bronchial lumen. The evidence that mast cells and mast cell-derived mediators play a role in allergic and non-allergic asthma is discussed. In allergic individuals, inhalation of specific allergens leads to mast cell degranulation and release of mediators. Many of the pathologic features of asthma may be attributed to the effects of mast cell-derived mediators. Their role is clear in allergic asthma and the presence of mast cell derived mediators in the plasma of individuals with exercise-induced and nocturnal asthma suggests involvement in other forms of asthma as well. PMID- 2884083 TI - The site of the defect in asthma. Neurohumoral, mediator or smooth muscle? AB - The nature of the underlying defect in asthma is still unclear. This article discusses where the primary problem might lie, starting with the assumption that it is likely to be in neurohumoral control, bronchial smooth muscle or cellular dysfunction with increased release of mediators. The weight of the evidence suggests that the latter is most likely. If true, the question of why this occurs still remains. PMID- 2884084 TI - Establishment of a radioimmunoassay of somatostatin in human plasma and in rat hypothalamus. AB - Synthetic cyclic somatostatin-14 (SRIF-14) was conjugated with carbodiimide onto hemocyanin to immunize rabbits, and anti-sera with high titers (1:5,000-100,000) and good sensitivity and specificity were obtained. 125I-Tyr1-SRIF was made and purified on CM-52 cation exchange column. The immunoreactive specific activity (SP.AC.) of the tracer was around 1013 mCi/mg, which was much higher than the commercial products and other reports. The sensitivity of the assay was around 16 pg/ml, and the detectable range 20-2000 pg/ml. Human plasma was freshly prepared in the presence of aprotinin. Rat hypothalamus was homogenized and extracted with HC1 followed by heating at 95 degrees C then centrifuged, and the supernatant assayed. The standard curves of the acetate buffer (ph 5.2), plasma doses, plasma recovery doses, hypothalamic extract doses, and hypothalamic extract recovery doses were all in good parallelism with each other. The recovery of SRIF from human plasma and from rat hypothalamus were 98.8 +/- 6.3% and 86.9 +/- 6.8%, respectively. The specificity of the antisera were very high, and they only cross react with H2-SRIF and Tyr1-SRIF at 15% and 170%, respectively, of the immunoreactivity to cyclic SRIF-14. The Scatchard plot of the binding data showed a straight line with a Kd of 3.52 X 10(-12)M and binding capacity of 4.06 X 10( 10)M. The intra- and inter-assay coefficient of variation were 4.5% and 12%, respectively. When the synthetic cyclic SRIF (Stilamin) was infused intravenously into normal volunteers, there were reproducible plasma time-dose curves of SRIF LI (SRIF Like Immunoreactivity), which revealed its plasma half life around 1.5 minutes, and metabolic clearance rate about 50 ml/kg/min. PMID- 2884085 TI - Endogenous excitotoxic agents. AB - Although glutamate and aspartate are among the most likely compounds to function as central neurotransmitters, and both can produce cell death in neonatal animals, the efficient uptake systems for these amino acids mean that exceptionally high concentrations are required for toxicity in adults. A better candidate for an endogenous neurotoxin is quinolinic acid, which produces cell death via activation of the N-methyl-aspartate receptors. Several differences of detail between the activity of quinolinate and N-methyl-aspartate may indicate the existence of subpopulations of the N-methyl-aspartate receptor. Another compound in the same 'kynurenine' pathway as quinolinate, kynurenic acid, is an antagonist of the excitatory and neurotoxic actions of quinolinate, and the overall excitability of the central nervous system and the occurrence of cell death may therefore result from a balance between the concentrations of quinolinate and kynurenate. PMID- 2884086 TI - [Estazolam and amitriptyline in the treatment of neurosis--a cross-over study on 136 patients]. PMID- 2884087 TI - [Prospective matched study of hysteria treated with systematic desensitization]. PMID- 2884088 TI - Treatment of alcoholism in Kuwait: a prospective follow-up study. AB - The outcome of routine drug-supportive psychotherapy treatment of 100 patients with alcohol-related problem in Kuwait's only psychiatric hospital was evaluated in four 6 month's intervals. Patients were assessed on 9 post-treatment questions reflecting improvement or deterioration. Correlation of follow-up changes to pre treatment data shows that non-Kuwaitis do better than Kuwaitis in resuming employment and social reintegration. Patients on chronic benzodiazepine prescription were less likely to become abstinent, had poor social re-integration and more re-admissions. Good relationships with the family were clearly associated with a better treatment outcome. Scores of weighted follow-up findings were calculated to assess patients' status at each follow-up. Progress during the whole follow-up period was measured by the direction of slope calculated from linear regression model for individual scores. The relationship between pre treatment conditions and patterns of follow-up was evaluated cross-sectionally (answers distribution) and longitudinally (direction of slope). A pattern of shift emerged where different patient groups crossed over to the opposite end of the score scale. Kuwait society's indulgent attitudes towards Kuwaiti patients with alcohol-related problems in employment have to be changed and utilization of the role of the Arab extended family in therapy is stressed. PMID- 2884089 TI - Stopping drug treatment in schizophrenia. PMID- 2884090 TI - [Clozapine-induced cholestatic liver lesions. A case study]. AB - During neuroleptic treatment with clozapine, transitory reversible rise in transaminases is not rare, while severe parenchymal damage with icterus has not previously been reported. Such a case is now described: a 54-year-old woman developed clozapine-induced cholestasis with severe liver damage. PMID- 2884091 TI - [Type II multiple endocrine neoplasms. Diagnosis, therapy and prognosis]. AB - From 1979 to 1986, seven patients with multiple endocrine neoplasia (MEN) type IIa and three with type IIb were treated. Nine had a C-cell carcinoma, one had C cell hyperplasia. None had hyperparathyroidism. Three patients had multiple mucous neuromas. Six patients had proven pheochromocytoma: adrenalectomy was performed in these six (unilateral or bilateral depending on whether the tumor was uni- or bilateral). All ten patients had a total thyroidectomy--three later required neck dissection for regional lymphnode metastases. One patient died from the consequences of diffuse liver metastases of a C-cell carcinoma. Extensive family screening is necessary with patients who have MEN type II, in order to discover early any occult disease carriers. In addition, MEN type II should be excluded in all patients who have C-cell carcinoma, pheochromocytoma or hyperparathyroidism. PMID- 2884092 TI - [Type II multiple endocrine neoplasms]. PMID- 2884093 TI - Effect of a single administration of somatostatin analogue (SMS 201-995) on GH, TSH and insulin secretion in patients with acromegaly. AB - The effect of a long-acting somatostatin analogue SMS 201-995 on GH secretion was investigated. Eleven acromegalic patients received a single dose of 50 micrograms SMS 201-995 administered subcutaneously, and plasma GH, IGF-I, GRF, TSH, IRI and blood glucose were determined at regular intervals. Nine of 11 patients had elevated basal plasma GH levels above 5 ng/ml. In all patients, plasma GH levels fell immediately from 39.5 +/- 17.3 ng/ml (mean +/- SEM) to 4.3 +/- 1.6 ng/ml (P less than 0.05) with a maximal inhibition of 82.9 +/- 3.3% of the basal levels and the suppression persisted for about 6 h of the observation period. IGF-I and GRF levels were not apparently altered. TSH and IRI levels also rapidly fell. Blood glucose levels fell slightly by 0.5 h. Ten of 11 patients had pain at injection sites. Except for this, no side effects were observed. Our results show that the new somatostatin analogue SMS 201-995 may inhibit GH hypersecretion in acromegalic patients for significant periods, suggesting that this agent can be a useful clinical tool for the treatment of acromegaly. PMID- 2884094 TI - Receptor dynamics and tyrosine aminotransferase induction during the course of chronic treatment of rats with glucocorticoid. AB - The changes in the cytosol glucocorticoid receptor (GR) content during a long term administration of a glucocorticoid were studied to examine the mechanism of the development of steroid hormone resistance. Dexamethasone (Dex) (0.2 microgram/ml and 2.0 micrograms/ml) was given to adrenalectomized rats, and the GR content was determined using the exchange assay 1, 10, 20 and 50 days after the start of administration. The activity of tyrosine aminotransferase (TAT) in the cytosol was also assayed as a measure of the biological responsiveness of these animals to the administered glucocorticoid. The dissociation constant (Kd) was elevated and the Bmaxs of the GR in the cytosol were decreased by the lower concentration of Dex. The Bmaxs decreased to 30% of the untreated controls within 24 h and this lower level was maintained as long as the hormone treatment continued. On the other hand, the cytosol obtained from animals treated with 2.0 micrograms/ml of Dex for 20-24 days did not show any measurable amount of binding to 3H-Dex. The activity of TAT was elevated 24 h after the administration of Dex but decreased gradually and steadily with time during the experimental period. To examine the biological potency of remaining GR in the liver cytosol, 2.0 micrograms/ml Dex was again administered after a long-term treatment. This treatment eliminated the remaining GR completely and induced TAT at almost the same rate as observed in the untreated control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884095 TI - A physiological role of E and F series prostaglandins in the regulation of TSH secretion. AB - The regulation of TSH secretion by E1, E2, E1 alpha and F2 alpha prostaglandins was studied by means of a monolayer culture system of dispersed rat anterior pituitary cells which was appropriately responsive to TRH, T3 and SRIF. PGEs and Fs induced significant increases in basal TSH release of the order of 30% at 10( 9) or 10(-8) to 10(-5) or 10(-4) M. Only PGEs accentuated the TSH release induced by a half maximal dose of TRH (10(-9) M) of the order of 60% in a dose dependent manner (10(-9) to 10(-6) M of PGEs), whereas PGFs did not. SRIF (10(-8) or 10(-9) M) alone failed to alter basal TSH release but did completely inhibit the TSH response to TRH (10(-9) M). SRIF also significantly inhibited both the increase in basal TSH release and the accentuation of the TSH response to TRH induced by PGEs (10(-6) M) but did not diminish the enhancement of basal TSH release induced by PGFs (10(-6) M). 7-oxa-13-prostynoic acid (PY1), a prostaglandin antagonist, which can act as an agonist in some systems, itself exhibited agonistic properties of PGEs with respect to basal and TRH induced TSH release. PY1 failed to inhibit the TSH release induced by all PGs, but partially inhibited the accentuated TSH response to TRH induced by PGEs. Indomethacin, PG synthetase inhibitor, did not affect basal or TRH induced TSH release in our system. These data suggest that PGs of the E and F series probably modulate TSH release via different mechanisms and that the PGE effect on basal TSH release differs from its augmentation of TRH induced TSH response. It is speculated that these effects of PGs may have physiological significance. PMID- 2884096 TI - Are gastrin and somatostatin involved in pathogenesis of gastric cancer? PMID- 2884097 TI - Antiepileptic drugs and the electroencephalogram. AB - The usefulness of electroencephalography (EEG) as an aid to diagnosis of seizure disorders is established, but its role as a guide to monitoring treatment is much less certain. For those patients with classical absences and 3-s spike wave activity there is a very close correlation between control of clinically detected seizures and EEG events. In some, but not all, patients with other seizure disorders there is a positive correlation between numbers of seizures and amount of interictal epileptiform activity (IEA). Intravenous benzodiazepines and phenytoin result in both acute seizure control and suppression of IEA. For seizures other than absences, and antiepileptic drugs (AEDs) given in the medium and long term, there is generally not a clear relationship between control of seizures and IEA. In studies of children whose epilepsy is in remission, persistent IEA has been associated with a higher risk of seizure relapse should AEDs be discontinued, but in adults the relevance of persistent IEA appears to be much less certain. Benzodiazepines and barbiturates result in increased fast activity. All AEDs may result in slowing of the dominant rhythm and increased slow activity. Carbamazepine, in particular, is often associated with apparent deterioration of background activity, even in the face of clinical improvement. Further studies are necessary to determine the mechanisms and significance of AED induced changes in EEG background activity. PMID- 2884098 TI - Comparative efficiency of Nuclepore filters of various pore sizes as used in digestion studies of tissue. AB - Some of the widely used techniques employed in assessing asbestos load in lung tissue include the use of digestion techniques, in which particulates are entrapped on a filter surface. However, the actual filtering efficiency of various pore sizes as applicable to collecting fibrous material has not been tested. The present study evaluates such filtration efficiency by using a series of back-to-back filters of various sizes. It was confirmed that fibers pass through the pores and that with the larger pore sizes an appreciable loss of small fibers can occur. It is suggested that a filter with 0.2-micron pore size offered a reasonable compromise for both filtration efficiency as well as sufficiently rapid filtration rates for most studies. PMID- 2884099 TI - Isolation and characterization of rat hepatic ascorbic acid-2-sulfatases. AB - Ascorbic acid-2-sulfatase was isolated from rat liver by a multistep procedure. DEAE Sephacel ion-exchange chromatography resolved crude ascorbic acid-2 sulfatase into cationic and anionic fractions. These fractions were purified 75- and 230-fold, respectively. The comparative biochemical properties suggest that arylsulfatase B is responsible for the cationic ascorbic acid-2-sulfatase activity, while arylsulfatase A appears to be responsible for the anionic ascorbic acid-2-sulfatase activity. Partially purified arylsulfatase A hydrolyzed ascorbic acid-2-sulfate at 4% the rate of p-nitrocatechol sulfate hydrolysis, while arylsulfatase B hydrolyzed ascorbic acid-2-sulfate at 0.6% the p nitrocatechol sulfate rate. PMID- 2884100 TI - Glutamine synthetase genes of pea encode distinct polypeptides which are differentially expressed in leaves, roots and nodules. AB - We have characterized the distinct polypeptides, primary translation products and mRNAs encoding glutamine synthetase (GS) in the various organs of pea. Western blot analysis of soluble protein has identified five distinct GS polypeptides which are expressed at different relative levels in leaves, roots and nodules of pea. Of the two GS polypeptides in leaves (44 and 38 kd), the 44-kd GS polypeptide is predominant and is localized to the chloroplast stroma. In roots, the predominant GS polypeptide is 38 kd. Upon Rhizobium infection of roots, three 37-kd GS polypeptides increase in abundance in the nodules relative to uninfected roots. cDNA clones encoding three different GS mRNAs have been characterized. Hybrid-select translation has identified three different GS primary translation products (49, 38 and 37 kd). Two cDNA clones (pGS134 and pGS341) are homologous to GS mRNAs most abundant in nodules which encode the 38- and 37-kd GS primary translation products. A third cDNA (pGS197) corresponds to a larger GS mRNA species specific to leaf poly(A) RNA, which encodes a 49-kd putative precursor to the mature chloroplast GS polypeptide. cDNA sequence analysis and Southern blot analysis of pea nuclear DNA identifies at least three genes encoding GS in pea which are related but distinct in structure and in vivo pattern of expression. PMID- 2884101 TI - Receptor coupled events in bradykinin action: rapid production of inositol phosphates and regulation of cytosolic free Ca2+ in a neural cell line. AB - The addition of bradykinin to NG115-401L cells grown on coverslips results in the generation of rapid transient increases in intracellular [Ca2+] and inositol phosphates. Changes in intracellular Ca2+, measured using the fluorescent indicator dye Fura-2, show two components; an initial rapid peak in [Ca2+]i which is essentially independent of extracellular Ca2+, and a sustained plateau dependent on the presence of extracellular Ca2+. Analysis of bradykinin stimulated production of [3H]inositol phosphates, by h.p.l.c., shows a rapid biphasic production of inositol 1,4,5-trisphosphate, inositol tetrakisphosphate and inositol bisphosphates, followed by a sustained rise in inositol 1,3,4 trisphosphate production. Quantitative measurements have indicated the presence of other, more polar, [3H]inositol-labelled metabolites which do not show major changes on bradykinin stimulation. The initial phase of inositol phosphate production parallels the rapid transient increase in intracellular [Ca2+], however, the second phase of inositol phosphate production occurs when intracellular [Ca2+] is declining and implies a complex series of regulatory events following receptor stimulation. Similar time courses of inositol 1,4,5 trisphosphate and Ca2+ signals provides supporting evidence that inositol 1,4,5 trisphosphate is the second messenger coupling bradykinin receptor stimulation to release of Ca2+ from intracellular stores. PMID- 2884102 TI - Nucleoplasmin cDNA sequence reveals polyglutamic acid tracts and a cluster of sequences homologous to putative nuclear localization signals. AB - Nucleoplasmin is the most abundant protein in the Xenopus oocyte nucleus. It is involved in histone storage and chromatin assembly and it has been used extensively to study the transport of proteins into the cell nucleus. We have isolated lambda gt11 phage containing nucleoplasmin cDNA and have determined the sequence of the entire protein coding region of 200 amino acids for one of the two genes. The translation product of the sp6 transcript of this cDNA has the same electrophoretic mobility as nucleoplasmin and is able to form pentamers. The protein sequence shows remarkable clusters of charged residues including a long polyglutamic acid tract which presumably constitutes the histone binding site. The short C-terminal domain which specifies nuclear entry contains four regions which are homologous to putative nuclear localization signals including two regions of homology to the nuclear migration signal of SV40 large T antigen. PMID- 2884104 TI - Molecular cloning of cDNA coding for rat proliferating cell nuclear antigen (PCNA)/cyclin. AB - The 'proliferating cell nuclear antigen' (PCNA), also known as cyclin, appears at the G1/S boundary in the cell cycle. Because of its possible relationship with cell proliferation, PCNA/cyclin has been receiving attention. PCNA/cyclin is a non-histone acidic nuclear protein with an apparent mol. wt of 33000-36000. The amino acid composition and the sequence of the first 25 amino acids of rabbit PCNA/cyclin are known. Using an oligonucleotide probe corresponding to the sequence of the first five amino acids, a cDNA clone for PCNA/cyclin was isolated from rat thymocyte cDNA library. The cDNA (1195 bases) contains an open reading frame of 813 nucleotides coding for 261 amino acids. The 3'-non-coding region is 312 nucleotides long and contains three putative polyadenylation signals. The mol. wt of rat PCNA/cyclin was calculated to be 28 748. The deduced amino acid sequence and composition of rat PCNA/cyclin are in excellent agreement with the published data. Using the cDNA probe, two species of mRNA (1.1 and 0.98 kb) were detected in rat thymocyte RNA. Southern blot analysis of total human genomic DNA suggests that there is a single gene coding for PCNA/cyclin. The deduced amino acid sequence of rat PCNA/cyclin has a similarity with that of herpes simplex virus type-1 DNA binding protein. PMID- 2884103 TI - A single point mutation in erbA restores the erythroid transforming potential of a mutant avian erythroblastosis virus (AEV) defective in both erbA and erbB oncogenes. AB - We have characterized the v-erbA and v-erbB oncogenes of td359, a transformation defective mutant of avian erythroblastosis virus (AEV) unable to transform erythroblasts, and the revertant r12, obtained after in vivo passage of the mutant. Molecular cloning, sequencing, construction of chimeric viruses and testing of their oncogenic capacities revealed that both oncogenes of td359 are mutated and biologically defective. The r12 virus, although still containing a mutant v-erbB gene, recovered its erythroid transforming potential by acquiring a highly active gag-erbA gene. These results demonstrate that two co-operating oncogenes, an active v-erbA and a defective v-erbB, can transform a cell type not transformed by either oncogene alone. Furthermore, a single amino acid substitution inactivated the td359 v-erbA protein and we show that its reversion led to the reactivation of the protein. This lesion is located in the same region as several previously described inactivating mutations of glucocorticoid receptors, suggesting that the structure/function relationship of the virally transduced form of the c-erbA/thyroid hormone receptor is closely similar to that of steroid hormone receptors. PMID- 2884105 TI - Independent mutations at the amino terminus of a protein act as surrogate signals for mitochondrial import. AB - Intracellular delivery of the mitochondrial F1-ATPase beta-subunit precursor from the cytoplasm into the matrix of mitochondria is prevented by deletion of its mitochondrial import signal, a basic amphipathic alpha-helix at its amino terminus. Using a complementation assay, we have selected spontaneous mutations which restore the correct in vivo localization of the protein containing the import signal deletion. Analysis of these mutations revealed that different functional surrogate mitochondrial targeting signals formed within a narrow region of the extreme amino terminus of the import signal deleted beta-subunit. These modifications specifically replace different acidic residues with neutral or basic residues to generate a less acidic amphipathic helix within a region of the protein which is accessible for interaction with the membrane surface. The observations of this study confirm the requirement for amphipathicity as part of the mitochondrial import signal and suggest how mitochondrial targeting signals may have evolved within the extreme amino terminus of mitochondrial proteins. PMID- 2884107 TI - Beta-blockers: use for arrhythmias. PMID- 2884108 TI - Circulating somatomedin-C levels and the effect of growth hormone-releasing factor on plasma levels of growth hormone and somatostatin-like immunoreactivity in obese children. AB - The effect of growth hormone-releasing factor (GRF) 1-44 on growth hormone and somatostatin release in plasma has been studied in 20 obese children. Twenty age and sex-matched children with normal weight served as controls. Mean peak growth hormone response in obese children after 1 microgram/kg body wt. GRF 1-44 was significantly lower than in controls (23.7 +/- 3.6 ng/ml vs. 41.1 +/- 3.0 ng/ml; P less than 0.01), as were mean integrated growth hormone response areas (1544 +/ 272 ng X ml-1 X 2 h vs. 2476 +/- 283 ng X ml-1 X 2 h; P less than 0.01). Mean plasma levels of somatostatin-like immunoreactivity did not change after GRF in both groups. Mean somatomedin-C levels in obese children were significantly higher compared to controls (1.6 +/- 0.4 U/ml vs. 0.86 +/- 0.4 U/ml; P less than 0.01). Somatomedin-C levels were not related to the integrated growth hormone responses. In conclusion there is no relation between somatomedin-C levels and the reduced growth hormone-releasing effect of GRF in obese children. GRF does not alter peripheral somatostatin-like immunoreactivity levels either in normal or obese children. PMID- 2884106 TI - Characterization and localization of the even-skipped protein of Drosophila. AB - On the basis of homeo box cross-homology we have isolated the pair-rule gene even skipped (eve) of Drosophila. The eve transcription unit appears to be less than 1.5 kb in length, and encodes a single mRNA of approximately 1.4 kb. The nucleotide sequence of genomic and cDNA clones indicates that the eve protein is composed of 376 amino acid residues, and that its homeo domain shares only approximately 50% amino acid identity with the homeo domains of previously characterized genes. Using antibodies raised against a beta-galactosidase fusion protein we show that the eve protein is distributed in a series of seven transverse stripes at the cellular blastoderm stage, and is localized primarily within the nuclear regions of those embryonic cells that express the gene. After gastrulation, seven weakly stained stripes of eve expression appear, resulting in a transient pattern that consists of a total of 14 evenly spaced stripes. Both the original and new stripes gradually disappear during germ band elongation. A second expression pattern emerges during neurogenesis, whereby eve protein is detected in discrete subsets of neurons in each of the ventral ganglia. PMID- 2884109 TI - Hypercalcaemia-induced acute renal failure as a presenting feature of T-cell leukaemia. AB - A 14-year-old patient presented with hypercalcaemia-induced acute renal failure. Investigation yielded a diagnosis of T-cell leukaemia. Chemotherapy resulted in complete remission, a return of serum calcium levels to normal and consequent improvement of renal function. PMID- 2884110 TI - Inhibition of the tyrosine hydroxylase system by MPTP, 1-methyl-4 phenylpyridinium ion (MPP+) and the structurally related compounds in vitro and in vivo. AB - MPTP, 1-methyl-4-phenyl-pyridinium ion (MPP+) and the structurally related compounds including N-methyltetrahydroisoquinilinium ion inhibited the tyrosine hydroxylase (TH) system in tissue slices of rat striatum at 10(-5) M. Mouse striatum is more susceptible to MPTP than rat striatum. A similar degree of inhibition by MPP+ was observed in the absence or presence of 1 mM dibutyryl cyclic adenosine monophosphate (DBcAMP) which stimulated the TH system about 3 fold. The results with the structurally related compounds of MPP+ indicate that both the pyridinium and the phenyl group are required for the inhibition of the TH system in tissue slices or rat striatum. Tetrahydroisoquinoline, a pyridinium compound related to dopamine (DA), was found to decrease TH and 3,4 dihydroxyphenylacetic acid in the striatum of mice after administration at a dose of 60 mg/kg/day s.c. for 8 days. It is suggested that either tetrahydroisoquinoline or N-methyltetrahydroisoquinoline, which is a DA-related pyridinium compound, could be one of the environmental or endogenous compounds inducing Parkinson's disease. PMID- 2884111 TI - MPTP-induced parkinsonian model in mice: biochemistry, pharmacology and behavior. AB - The effects of MPTP administered to mice were examined biochemically and pharmacologically. The dopamine level in the striatum of the mice injected with MPTP decreased markedly, but recovered to 50% of the control level 6 weeks later. Amine fluorescence showed a decrease in the amount of amine especially in the lateral part of the striatum. Of the four neuropeptides, only the concentration of somatostatin changed with time. These findings indicate that the time elapsed after MPTP treatment should be taken into consideration when MPTP-treated mice are used as a parkinsonism model. Six weeks after MPTP treatment, the concentration of the striatal muscarinic cholinergic receptor decreased significantly but recovered to the normal level after the administration of L dopa. Such a change was not detected with the dopamine D2-receptor. The therapeutic efficacy of medication in MPTP-treated mice as examined by the pole test showed that L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), which is considered to be the precursor of norepinephrine, enhances the effect of L-dopa. PMID- 2884112 TI - Increased visualization of antral gastrin-producing G-cells after acute stimulation of gastrin release in the rat. AB - The effect of acute stimulation of gastrin release on the number of antral gastrin-producing G-cells stained by conventional immunohistology was investigated in two experimental models. The substituted benzimidazole derivate BY 308 was administered at a dosage that induces complete achlorhydria and thereby led to marked hypergastrinaemia. Two hours after drug administration, antral G-cell density was increased by 14% and 35% in 12-h and 48-h fasted rats, respectively. Both serum gastrin levels and G-cell density further increased after 3 and 8 days' treatment with BY 308 whereas the somatostatin (D)-cell count did not change prior to 8 days' administration. In the isolated, vascularly perfused rat stomach, acetylcholine was perfused for 36 min; this regimen increased gastrin release four-fold and enhanced the G-cell count by 24% whereas 8 min acetylcholine perfusion did not alter G-cell density significantly but stimulated gastrin output. The results of this study suggest that acute changes in the secretory activity of the gastrin cell are accompanied by an alteration of the staining characteristics thus indicating that an increase in the antral G cell count does not solely depend upon formation of new cells. PMID- 2884113 TI - Human renovascular effects of dopexamine hydrochloride: a novel agonist of peripheral dopamine and beta 2-adreno-receptors. AB - The effects of dopexamine on the renal circulation have been examined to show whether any augmentation of renal blood flow (RBF) was secondary to the effect of the drug on cardiac output (CO) or whether it had any additional direct renal vasodilator activity. Eight male patients with mild to moderate hypertension, who were undergoing renal vein catheterization for renin estimation, were studied. Dose related increments in RBF (baseline (B) = 504 ml X min-1; after treatment (D) = 605 ml X min-1), CO (B = 5.9 l X min-1; D = 6.7 l X min-1), heart rate (B = 77 beats/min; D = 100 beats/min) and systolic blood pressure (B = 143 mmHg; D = 166 mmHg) were observed on administration of dopexamine 3 micrograms X kg-1 X min 1, with insignificant changes in diastolic blood pressure (B = 84.4 mmHg; D = 90 mmHg) and total peripheral resistance (B = 17.85; D = 17.25 Units). There was a slight but significant reduction in renal vascular resistance (B = 20.59, D = 18.75). The ratio of RBF to CO (%) confirmed that the increase in RBF due to dopexamine hydrochloride was greater that attributable to the increase in CO or perfusion pressure alone (RBF/CO B = 8.5%, D = 9%), consistent with selective renal vasodilatation. The fall in renin activity and lack of systemic vasodilatation suggest that this was a DA1-receptor mediated effect. PMID- 2884114 TI - Effect of concomitant food intake on absorption kinetics of fenoldopam (SK&F 82526) in healthy volunteers. AB - Eight healthy volunteers participated in an open crossover study to assess the effect of a standardised meal on the systemic availability of a single oral dose of fenoldopam mesylate 100 mg. Subjects were studied on four separate occasions, twice fasting and twice fed in randomised, balanced order. Plasma and urine samples were obtained before and at regular intervals up to 25 h post dose. Measurement of fenoldopam (SK&F 82526) and its 8-sulphate metabolite (SK&F 87782) were by means of HPLC-EC analysis. Area under the plasma concentration time curve (AUC) and maximum detected plasma concentration (Cmax) for fenoldopam and SK&F 87782 were significantly reduced whereas time to maximum concentration was significantly increased with food. Using AUC's for fenoldopam and SK&F 87782, mean relative bioavailabilities were 35% and 81% respectively under fed compared with fasting conditions. Twenty-four hour excretion of fenoldopam was significantly reduced with food, but excretion of SK&F 87782 was apparently unchanged. Mean relative bioavailabilities calculated from these data were 83% and 86% respectively. Relatively large inter-subject variability in AUC and Cmax were seen, but intra-subject variability was not marked. Mild symptoms associated with vasodilation were reported on all study days. PMID- 2884115 TI - Psychotropic drug utilization patterns in a metropolitan population. AB - Psychotropic drug intake by a random sample of citizens of the city of Munich aged 30-69 years has been assessed. A 1-week prevalence of 9.3% for all psychotropic drug users was found, benzodiazepines accounting for approximately two-thirds (6.6%) of the users. Two-thirds of drug users were women. Drug use in both sexes increased with age. The doses of benzodiazepines prescribed in most cases were less than 10 mg diazepam equivalent per day. Intake of benzodiazepines in combination with analgesics or alcohol (greater than or equal to 40 g/day) did not appear to represent a major problem. Multiple logistic regression analysis showed that the number of chronic diseases was the strongest predictor of benzodiazepine intake in men, whereas stress and age determined intake in women. Long-term use seemed to be relatively rare at 11% of all benzodiazepine users, so it was not considered to be a severe public health problem. PMID- 2884116 TI - Effects of bisoprolol on blood pressure, serum lipids and HDL-cholesterol in essential hypertension. AB - Fifty patients with essential hypertension WHO Grades I-II have been treated for 3 months with bisoprolol, a new selective beta blocker, in doses up to 40 mg once daily. Forty-three patients reached the preset target diastolic blood pressure of less than or equal to 90 mmHg on a mean daily dose of 16.8 mg bisoprolol. There was no effect on serum lipids and HDL-cholesterol during the study. The side effects were mild and were those usually associated with beta-blocking therapy. PMID- 2884117 TI - A peripheral sympathetic component in inflammatory hyperalgesia. AB - Non-steroidal anti-inflammatory drugs (NSAID) only partially inhibit the hyperalgesia in the inflammation induced by carrageenin in the hind rat paw, one of the most frequently used nociceptive tests. We now report that either the guanethidine depletion of peripheral sympathomimetic amines or the treatment with adrenoceptor antagonists (beta-blockers) and a specific dopamine (DA)-1 antagonist (SCH 23390) significantly reduced carrageenin hyperalgesia. These antagonists also abolished the rat paw hyperalgesia induced by several sympathomimetic amines as well as that induced by a selective DA-1 agonist, SKF 38393. Blockade of uptake-1 by cocaine potentiated the hyperalgesia induced by carrageenin and sympathomimetic amines. We conclude that there is a sympathetic component, possibly mediated by a DA-1 type receptor in carrageenin-induced hyperalgesia. This component may predominate in certain types of pain not sensitive to NSAID. If so, selective peripheral DA-1 antagonists could be developed as a novel class of analgesics. PMID- 2884118 TI - Pharmacological evaluation of the beta-adrenoceptor agonist and thromboxane antagonist properties of N-substituted trimetoquinol analogues. AB - The beta 1- and beta 2-adrenoceptor agonist and U46619 (a thromboxane A2 agonist) antagonist properties of trimetoquinol (TMQ, I) and its optical isomers, and N substituted TMQ analogues (methyl, II; 2-hydroxyethyl, III; cyclic sulfite N-2 chloroethyl, IV; 2-chloroethyl, V; benzyl, VI) were studied in guinea pig atria and trachea and rat aorta, respectively. All compounds gave concentration dependent responses in atria and trachea, and the rank order of beta-adrenoceptor agonist potency was I greater than II greater than III greater than IV greater than V greater than VI. Whereas N-substitution reduced potency for beta-agonism, the beta 2/beta 1-selectivity ratio was enhanced by increasing the size of the N substituent. All analogues possessed equal or greater (up to 41-fold more) beta 2 selectivity than I. Propranolol was a competitive antagonist of selected TMQ analogues in guinea pig trachea and atria, thus confirming the beta-adrenoceptor actions of these drugs. The optical isomers of TMQ gave a rank order of agonist potency of S(-)-TMQ greater than R(+)-TMQ, and a beta 2/beta 1-selectivity equal to or greater than racemic-TMQ. Each TMQ analogue also blocked the contractile responses of U46619 in rat aorta in a competitive manner, and the rank order of inhibition of U46619-induced contraction in rat aorta was I greater than VI greater than II = III greater than IV greater than V. N-Benzyl TMQ (VI) possessed the greatest potency for U46619 blockade and beta 2/beta 1-selectivity ratio of the N-substituted analogues. The results show that varying the N-substituents on TMQ produces compounds which retain beta 2-selectivity and give a different activity profile for beta-adrenoceptor activation vs. endoperoxide/thromboxane A2 antagonism. PMID- 2884119 TI - Adrenergic and 'non-adrenergic' contributions to the two-component tetanus in the rat vas deferens. AB - Nerve-induced contractions of rat isolated vas deferens were examined to determine how the rapid and slow twitch phases summate to produce the two component tetanus. The rapid phase (time to peak, 200-300 ms) had a latency of 35 50 ms and was selectively abolished by nifedipine but not verapamil. The slow phase (time to peak, 500-650 ms), as seen in the presence of nifedipine, had a latency of 100-200 ms. During a train of pulses at 0.5-2 Hz, its size declined rapidly and its latency lengthened. The rapid phase responses at these frequencies were progressively potentiated to a peak after 12-40 s, a time similar to the peak of the secondary tetanic component at 5 Hz. Doses of verapamil which abolished both this potentiation and the secondary tetanic component did not block the slow twitch phase. The results indicate that the primary tetanic component is a summation of 'non-adrenergic' (rapid phase) and direct adrenergic (slow phase) contractions. In contrast the secondary increase in tetanic tension results largely from the alpha 1-adrenoceptor induced potentiation of the rapid non-adrenergic twitch mechanism. The mechanisms for the two phases and for the potentiation each appear to involve different calcium sources. PMID- 2884120 TI - Role of the dopaminergic nigrostriatal pathway in methamphetamine-induced depression of the neostriatal serotonergic system. AB - The prevention of the decrease in neostriatal tryptophan hydroxylase (TPH) activity with a single dose of methamphetamine (MA) was attempted by lesioning the nigrostriatal dopaminergic projections with bilateral nigral injections of 6 hydroxydopamine (6-OHDA). The rats were injected with MA (10 mg/kg) 11 days later, and killed 3 h after the injection. The 6-OHDA lesions prevented the decrease of TPH activity in the neostriatum, while the decrease of enzyme activity was slightly attenuated in the hippocampus and unaffected in the frontal cortex. This study demonstrates: that the attenuation of TPH activity can be prevented in a selected brain area by destroying its dopaminergic afferents, and implicates central dopamine (DA), or its metabolite, in the decrease in central TPH activity observed after a single injection of MA. PMID- 2884121 TI - The dopamine autoreceptor agonist B-HT 920 inhibits in vivo dopamine release into the cerebroventricular system of cats. AB - In anesthetized cats the dopamine autoreceptor agonist B-HT 920 (6-allyl-2-amino 5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]-azepine), 1 mg/kg i.v., greatly decreased the amount of dopamine in cerebroventricular perfusates. This effect was antagonized by a low dose (50 micrograms/kg i.v.) of haloperidol, but not by the alpha 2-adrenoceptor blocker idazoxan. Our observations provide evidence that B HT 920 inhibits brain dopamine release in vivo and may be therapeutically valuable in diseases presumed to be accompanied by a predominance of brain dopamine activity, such as Huntington's disease, mania and schizophrenia. PMID- 2884122 TI - Stimulation of soluble guanylate cyclase by endothelium-derived relaxing factor from cultured endothelial cells. AB - Bovine endothelial cells, grown on microcarrier beads and superfused with a saline solution, were stimulated with thimerosal or bradykinin to release endothelium-derived relaxing factor (EDRF). EDRF activity in the effluent was assayed in endothelium-denuded rabbit aorta. The stimulation of purified soluble guanylate cyclase in test tubes by the EDRF-containing effluent amounted to 90 fold of basal activity and its time course correlated with that of the dilator response of the aorta. After preincubation of endothelial cells with gossypol the EDRF-induced dilator response as well as the stimulation of guanylate cyclase was suppressed. PMID- 2884123 TI - Phentolamine reverses NPY-induced inhibition of insulin secretion in isolated rat islets. AB - It has been shown that the rodent pancreas is innervated by neuropeptide Y (NPY) nerves, some of which are adrenergic, and that NPY inhibits glucose-induced insulin secretion in vivo in the mouse and that from isolated rat islets in vitro. We now investigated whether the alpha-adrenoceptor antagonist phentolamine affects the inhibitory action of NPY on insulin secretion from isolated rat islets. It was found that NPY dose dependently inhibited insulin secretion stimulated by glucose (11.1 mM). At a concentration of 10(-7) M, NPY totally abolished the insulin secretory response to glucose. It was also found that incubation with the alpha-adrenoceptor antagonist phentolamine (10(-6) M) itself enhanced the insulin secretion at 3.3 mM but not at 16.7 mM glucose. Moreover, phentolamine counteracted the inhibitory action of NPY. Thus, at 10(-8) M, NPY could no longer inhibit insulin secretion when phentolamine (10(-6) M) was present, whether 3.3 mM or 11.1 mM glucose was present. In contrast, somatostatin (10(-7) M) could inhibit insulin secretion, both in the presence and absence of phentolamine (10(-6) M); this showed that phentolamine does not reverse all types of inhibition. However, when the dose of phentolamine was decreased to 10(-7) M, the inhibitory action of NPY on glucose-induced insulin secretion was retained indicating that the reversal of the NPY effect by phentolamine is a competitive effect. It is concluded that NPY inhibits glucose-induced insulin secretion by a direct action on the islets, and that phentolamine reverses this inhibitory action of NPY in a competitive manner. PMID- 2884124 TI - Intrathecally administered dynorphin-(1-17) modulates morphine-induced antinociception differently in morphine-naive and morphine-tolerant rats. AB - The intrathecal (i.t.) administration of morphine, but not of dynorphin-(1-17), dose dependently inhibited thermal nociceptive responses to radiant heat. In morphine-naive rats, i.t. dynorphin-(1-17) slightly antagonized morphine analgesia but potentiated it in morphine-tolerant rats. These data provide further evidence that dynorphin-(1-17) modulates the effects of exogenously administered opiates differently, depending upon whether the animals are opiate naive or opiate-tolerant. PMID- 2884125 TI - Topical timolol, at conventional, unilateral doses causes bilateral ocular beta blockade in rabbits. AB - The studies described herein reveal that unilateral 0.3% and 1% doses of timolol produce marked beta-adrenoceptor blockade in treated and in contralateral eyes which did not receive timolol. This indicates that unilateral, conventional topical doses of timolol administered to rabbits cause bilateral ocular beta adrenoceptor blockade. In addition, 0.1% and 1% doses of timolol applied to one eye resulted in blockade of cardiovascular beta-adrenoceptors. Thus, the most likely explanation for bilateral ocular beta-blockade would be systemic absorption of timolol from the treated eye and redistribution to the fellow eye. Since contralateral eyes would not provide an adequate control in circumstances where a large dose of timolol is administered unilaterally, caution must be exercised in interpreting data obtained in laboratory animals with doses of timolol similar to those employed clinically. A 0.01% dose of timolol appears adequate to achieve marked, unilateral ocular beta-adrenoceptor blockade in rabbits. PMID- 2884127 TI - Kindling-induced changes in EEG recorded during stimulation from the site of stimulation. III. Direct pharmacological manipulations of the kindled amygdala. AB - In our previous studies, we hypothesized that activation and subsequent collapse of GABA-mediated inhibition during tetanus is an important seizure-triggering mechanism in the kindled epileptogenic focus. To examine this hypothesis, in the present study, we investigated the effects of pharmacological manipulations of the kindled amygdala with several drugs, and measured the kindled seizures as well as the EEG events during tetanus. The results obtained were: (i) The selective GABA-A agonist, muscimol (1 and 5 nM/1 microliter), suppressed kindled seizures in a dose-dependent fashion, and the 5 nM muscimol significantly prolonged EEG suppression and reduced the number of oscillations in the subsequent rhythmic synchronous discharge. Similar effects followed systemic injection of diazepam (2 mg/kg). (ii) The selective GABA-B agonist, baclofen (5 nM), had no effect on kindled seizures nor on the EEG events during tetanus. (iii) The NMDA antagonist, 2-amino-5-phosphonovaleric acid (80 nM), significantly reduced the afterdischarge duration and significantly delayed the appearance of the rhythmic synchronous discharge. However, these effects were not observed immediately, but 24 to 72 h after microinjection. (iv) The muscarinic cholinergic antagonist, atropine (40 and 80 nM), suppressed kindled seizures in a dose dependent fashion, but the atropine caused marked synchronous discharge both in the awake resting EEG and during tetanic stimulation. We conclude that the GABA-A system, including the benzodiazepine system, is more involved in the seizure triggering mechanism of amygdala kindling than the GABA-B system, that there is an interaction between the GABA-A and NMDA system, and that the cholinergic participation is independent of the primary seizure-triggering mechanisms. PMID- 2884126 TI - Catecholaminergic neurons containing GABA-like and/or glutamic acid decarboxylase like immunoreactivities in various brain regions of the rat. AB - The coexistence of immunoreactivities for tyrosine hydroxylase (TH) and glutamic acid decarboxylase (GAD) and/or gamma-aminobutyric acid (GABA) was revealed in various brain regions in colchicine-injected and untreated rats, using the peroxidase-antiperoxidase method. Consecutive 40 micron thick Vibratome sections were incubated in different antisera and those cells which were bisected by the plane of sectioning so as to be included at the paired surfaces of two adjacent sections were identified. The coexistence of the immunoreactivities for TH and GAD or GABA in the same cell could thus be determined by observing the immunoreactivity of the two halves of the cell incubated in two different antisera. In the olfactory bulb, retina, diencephalon, mesencephalic central grey and cerebral cortex, many TH-like immunoreactive neurons also showed GAD-like or GABA-like immunoreactivity, whereas in the substantia nigra, ventral tegmental area and locus ceruleus none of TH-like immunoreactive neurons showed either GAD like or GABA-like immunoreactivity. In the olfactory bulb, retina and cerebral cortex, the majority of the TH-like immunoreactive neurons were also GAD-like or GABA-like immunoreactive. In the diencephalon of colchicine-injected rats, at least one-third of the TH-like immunoreactive neurons were GAD-like immunoreactive. Using serial 0.5 micron thick plastic-embedded sections, it was shown that immunoreactivities for three antigens, GAD, GABA and TH could occur in the same neurons in the olfactory bulb. These observations indicate the possible coexistence of two classical transmitters. GABA and catecholamine, in various brain regions of the rat. PMID- 2884128 TI - [Characteristics of the presynaptic action of harman and its derivatives compared to benzodiazepine tranquilizers]. AB - In experiments on superfused cerebral hemispheric cortex slices of rats preincubated with 3H-gamma aminobutyric acid (3H-GABA), 3H-serotonin (3H-ST) or 3H-noradrenaline (3H-NA) it was shown that benzodiazepine tranquillizers (chlordiazepoxide and diazepam at the concentration of 3 X 10(-5) M) fail to change basal and slice electrostimulation-induced release of 3H-GABA, depress presynaptic release of 3H-NA and significantly enhance impulse release of 3H-ST. In contrast to benzodiazepine tranquillizers, harmane and its derivatives administered at the same concentration enhance slice electrostimulation-induced release of 3H-GABA, 3H-ST and 3H-NA. PMID- 2884129 TI - [Effect of the atypical neuroleptics carbidine and sulpiride on dopamine biosynthesis in the synaptosomes of the nucleus accumbens septi in rats]. AB - Neurochemical mechanisms of actions of atypical neuroleptics carbidine (a derivative of gamma-carboline) and sulpiride on dopamine (DA) biosynthesis in synaptosomes of the nucleus accumbens septi of the rat brain were studied. Carbidine caused a dose-dependent decrease of the animals' locomotor hyperactivity induced by apomorphine (1 mg/kg). Both carbidine and sulpiride administered in a dose of 5 mg/kg increased the activity of tyrosine hydroxylase in synaptosomes of the nucleus accumbens septi. In vitro carbidine decreased and sulpiride exerted no effect on the activity of tyrosine hydroxylase of the nucleus accumbens septi synaptosomes. Carbidine as well as sulpiride in vitro failed to modify the release of 3H-DA from superfused synaptosomes. At the same time, both in vivo and in vitro, the two neuroleptics reduced the inhibitory effect of DA on the 3H-DA release from synaptosomes of the nucleus accumbens septi and on the activity of tyrosine hydroxylase. PMID- 2884130 TI - The effect of the natural protein inhibitor on H+-ATPase hepatoma 22a mitochondria. AB - The uncoupler-induced inactivation of H+-ATPase in hepatoma 22a and mouse liver mitochondria has been studied. The dependence of this process on delta microH, and pH and ATP was established. The inactivated ATPase could be reactivated at alkaline pH values in the absence of ATP. These data indicate that the inactivation is apparently caused by the natural protein inhibitor. ATP- and pH dependent decrease of ATPase activity is also observed after Lubrol-WX disruption of mitochondria. It can be proposed that practically all ATPase molecules in hepatoma mitochondria are in a catalytically active complex with the protein inhibitor. At low delta microH this complex is inactivated via reversible pH dependent and irreversible ATP-dependent rearrangements. The pH-dependent rearrangement of the isolated protein inhibitor from hepatoma mitochondria is also observed. PMID- 2884132 TI - [Changes in the functional-morphological indices of somatostatin-producing D cells of the gastric antrum induced by vagus nerve stimulation]. PMID- 2884131 TI - Disruption of the Lys-290--Glu-342 salt bridge in human alpha 1-antitrypsin does not prevent its synthesis and secretion. AB - The object of this work was to test the hypothesis that failure to secrete the Z variant of human alpha 1-antitrypsin is related to the loss of a particular structural feature, the Lys-290 to Glu-342 salt bridge. Oligonucleotide-directed mutagenesis was used to disrupt the salt bridge by substituting a glutamic acid for lysine at residue 290. RNA transcripts prepared from this mutant DNA and from the normal cDNA were both able to direct the synthesis of protein in a cell-free system and after injection into Xenopus oocytes. Furthermore, the constructed mutant alpha 1-antitrypsin was secreted as readily as the normal inhibitor. PMID- 2884134 TI - Re-evaluation of the obstetrical risk for the older primipara. AB - The obstetric data relating to 92 older primiparas (OP) treated as regular obstetric patients and data relating to 92 older multiparas (OM) are compared to a previous study of 98 OP, which led to the conclusion that OP should not be managed as high-risk patients during gestation. No difference was found between the two periods regarding complications of pregnancy, gestational age and birth weight, onset of labor, perinatal morbidity and mortality. Nevertheless, cesarean deliveries were significantly higher in the study group. It seems that the conservative attitude towards OP during pregnancy is justified, but at labor, more rigid indications for cesarean section should be applied to establish objective patient care. PMID- 2884133 TI - Takayasu's arteritis and pregnancy: a case of deleterious association. AB - The association of pregnancy with Takayasu's arteritis is almost always uneventful. A case with high values of maternal blood pressure (BP) and severe intra-uterine growth retardation (IUGR), submitted to aggressive management with the delivery of a live fetus at 30 weeks, is presented. PMID- 2884135 TI - Outcome of pregnancy following investigation and treatment of infertility. AB - We studied 500 women who conceived after investigation and treatment for different infertility problems and compared the outcome of the 5 infertility groups (Group 1 to 5), the ovulatory dysfunction (Group 1), male infertility (Group 2), A.I.D. (Group 3), tubal surgery and IVF (Group 4) and no treatment (Group 5) with the outcome in the hospital group during a period of 3 years. The incidence of abortion in Group 3 is significantly higher (13.8%), the incidence of ectopic pregnancy is significantly higher in Group 4 (21.7%) as compared with the incidence in the hospital group (P less than 0.01). The rate of pre-existing hypertension and gestational diabetes is significantly higher in all the 5 infertility groups as compared with the incidence in the hospital group (P less than 0.05). The incidence of preterm labor in general is less in the infertility group as compared with the incidence in the hospital group (P greater than 0.05). The incidence of older women, multiple pregnancy, induction of labor, operative deliveries, fetal distress, low Apgar score, babies with birth weight below the tenth centile were higher in the infertility groups (P less than 0.05). But the perinatal mortality or major or minor fetal anomalies were not significantly different in the infertility groups as compared with the rate in the hospital groups (P greater than 0.05). PMID- 2884136 TI - Hypergonadotropic amenorrhea--etiology and outcome in 93 young women. AB - Ninety-three cases of amenorrheic women aged 40 years or less in whom serum FSH concentrations were found to be greater than 20 units/l have been reviewed. The etiology and diagnosis of this uncommon but serious condition and the potential for spontaneous recovery of ovarian follicular activity (17.1%) are discussed. Management is reviewed in the light of ultrasonic, karyotypic and immunological findings. PMID- 2884137 TI - Estrogen receptors in breast cancer--therapeutic response to the treatment of recurrences. AB - The authors analyze estrogen receptors in 501 cases of breast cancer and the therapeutic response achieved with treatment of patients who relapsed. The method utilized to determine the presence of estrogen receptor was cytosol protein counting and Dextran coated charcoal (DCC) saturation analysis. Patients were treated with chemotherapy when the primary tumor was estrogen-receptor negative. If receptor was present, anti-estrogen drug (Tamoxifen) was added. Patients previously treated with the anti-estrogen presented a better response to anti estrogen therapy and a lower recurrence rate. Recurrences were more frequent in estrogen receptor negative cases and better responses to treatment were found in estrogen receptor positive ones. PMID- 2884138 TI - Prophylactic topical cefamandole in radical hysterectomy. AB - From July 1, 1978 to June 30, 1984, 45 radical abdominal hysterectomies were performed by the authors at Tripler Army Medical Center. Management was uniform except for the use of prophylactic antibiotics. Three patterns of practice were identified: Group I, no antibiotics were used; Group II, intravenous (i.v.) antibiotics were given in the induction room and for less than 48 h post-surgery; Group III, prophylactic i.v. antibiotics were given and the surgical site was also irrigated with a cefamandole and saline solution. The three groups were found to be similar with regard to age, parity, weight-height index, pre- and postoperative hematocrit, pre-operative white blood cell count, operative and anesthesia times, estimated blood loss, and amount of blood transfused. Groups I and II had a higher surgical site infection rate (87.5% and 63.6%, respectively) than Group III (3.8%). The mean 10-day fever index in degree hours was 109 for Group I, 71 for Group II, and 30 for Group III (P less than 0.001). Irrigation of the surgical site with a cefamandole and saline solution in addition to i.v. antibiotics decreases the infectious morbidity of radical hysterectomy. PMID- 2884139 TI - Serum ovarian steroids, prolactin and prostaglandin metabolites in women using the inert intrauterine device. AB - Serum levels of 17 beta estradiol, progesterone, prolactin and metabolites of prostaglandins E2 and F2a were investigated in 18 healthy women before and after the insertion of a Saf-T-Coil intrauterine device. The results suggest that the presence of an intrauterine device may cause hormonal changes affecting the luteal phase of the menstrual cycle. PMID- 2884140 TI - Clinical evaluation of steroid receptors in ovarian neoplasms. AB - Estrogen and progesterone receptors were estimated in a total of 25 ovarian neoplasms. None of the benign tumors showed steroid receptors. In malignant tumors serous tumors were more often receptor positive than the mucinous. Receptor levels were correlated with the staging of the disease, menstrual status and the resectability of the tumor. The response to chemotherapeutic drugs was better in patients with low estrogen and progesterone receptors as compared to those with high levels. The latter group showed a definite response to progesterone treatment in vitro. These are the group of patients who may benefit by combination of hormones and chemotherapeutic drugs. PMID- 2884141 TI - Procidentia in the newborn. AB - Complete uterine prolapse was noted shortly after birth in a female infant with a meningomyelocele at the level of the iliac crest with a palpable dimpled defect caudal to the primary lesion. The vagina and uterus were restored to their normal position with a rubber nipple placed into the vagina. The prolapse resolved on the sixth day of life after a repair of the meningomyelocele. Thus, conservative therapy with temporary support provides a satisfactory solution for newborn procidentia. PMID- 2884142 TI - Abscess formation post cesarean section due to a piece of latex glove. AB - Pelvic abscesses may develop after retention of foreign bodies. A case is presented in which during drainage of a post cesarean section pelvic abscess a small piece of a latex glove was recovered. The formation of pelvic abscesses due to foreign bodies is discussed. PMID- 2884143 TI - Maternal mortality--a twelve-year survey at the University of Ilorin Teaching Hospital (U.I.T.H.) Ilorin, Nigeria. AB - This paper concerns an analysis of maternal death at the University of Ilorin Teaching Hospital (U.I.T.H.) Ilorin over a 12-year period (1972-1983). There were 138,577 births and 624 deaths making a maternal mortality rate of 4.50 per 1000 births. Hemorrhage, ruptured uterus and obstructed labor were the major direct obstetric causes of death. The most important indirect causes were cerebrospinal meningitis, pulmonary infections and fulminating hepatitis. The main avoidable factors were ineffective and cumbersome blood transfusion services; poor management of the third stage of labor; large number of unbooked patients and poor delivery room structure encouraging sepsis. Suggestions are made for a more integrated type of maternity services in our hospital, health education programs for the public and particularly the expectant women and availability of an effective blood bank service within the maternity hospital premises for prompt treatment of patients requiring emergency blood transfusion. The analysis underlines the great problem of maternal mortality in the developing world. PMID- 2884144 TI - Viral hepatitis as a major cause of maternal mortality in Addis Ababa, Ethiopia. AB - Causes of maternal mortality were investigated in Addis Ababa, Ethiopia, from September 1981 to September 1983. Viral hepatitis ranked third among the leading causes of maternal mortality behind septic abortion and puerperal sepsis. There were 26 deaths from viral hepatitis during the 2-year study period for a hospital maternal mortality rate of 91.0 per 100,000 live births. Although 30% of women who died of all maternal causes received antenatal care in Addis Ababa, only 13% of women who died from viral hepatitis in our hospital study received antenatal care. Low socio-economic status (SES) has been shown to be associated with low antenatal care utilization and with an increased risk of protein malnutrition. Malnutrition is considered a predisposing factor for liver damage. Suggestions for reducing hepatitis transmission and maternal mortality through education, better hygiene, and improved sanitation are discussed. PMID- 2884145 TI - Recombinant DNA technology and low-density lipoprotein receptor defects. PMID- 2884146 TI - An overview of the biochemistry and pharmacology of glutamatergic and GABA-ergic neurotransmission. PMID- 2884147 TI - Interactions between neurons and glia in glutamate/glutamine compartmentation. PMID- 2884148 TI - Tracing of neurons with glutamate or gamma-aminobutyrate as putative transmitters. PMID- 2884149 TI - Localization and function of glutamine synthetase and glutaminase. PMID- 2884150 TI - Function of gamma-hydroxybutyrate: a putative neurotransmitter. PMID- 2884151 TI - Excitatory receptors and their role in excitotoxicity. PMID- 2884152 TI - Loratadine (SCH29851) 40 mg once daily versus terfenadine 60 mg twice daily in the treatment of seasonal allergic rhinitis. AB - Seventy patients received loratadine 40 mg once daily, terfenadine 60 mg twice daily, or placebo in a 14-day, double-blind, randomized study. Four nasal and four non-nasal symptoms associated with allergic rhinitis were evaluated. At the endpoint (the last evaluable visit), the mean total scores of combined nasal and non-nasal symptoms decreased (improved) from the baseline by 51.8% and 55.7% with loratadine and terfenadine, respectively, but increased (worsened) by 6.1% with placebo. There was a significant difference between both the loratadine and terfenadine treatment groups and the placebo group (P = 0.001) but not between the active medication groups (P = 0.608). Overall therapeutic response was good or excellent in 14 of the 23 patients given loratadine, in 18 of the 24 given terfenadine and in none of the 23 given placebo. The difference between each active medication group and the placebo group was significant (P less than or equal to 0.01) but there was no significant difference between the two active treatment groups (P greater than 0.35). No loratadine patient had any adverse side-effects. Sedating effects occurred in one terfenadine patient, headache in one placebo patient and two terfenadine patients (one terfenadine patient with severe headache discontinued treatment), and dyspepsia in two placebo patients. No anti-cholinergic effects occurred in this study. Loratadine 40 mg once daily was effective and safe in the relief of symptoms of allergic rhinitis. PMID- 2884153 TI - Cell lineage analysis of pancreatic islet development: glucagon and insulin cells arise from catecholaminergic precursors present in the pancreatic duct. AB - We have previously reported that cells transiently expressing tyrosine hydroxylase (TH), the first enzyme of the catecholamine biosynthetic pathway, are present in the pancreas of mouse embryos from prenatal Day 11 (E11) and that, at E12, some TH cells contain glucagon. Cells containing TH were also found in adults which, unlike the TH cells of embryos, did not contain glucagon (G. Teitelman, T. H. Joh, and D. J. Reis (1981). Proc. Natl. Acad. Sci. 78, 5225). These findings suggested to us that the TH cells of embryonic pancreas were the precursors of glucagon cells of adults. In this study we used immunocytochemical and autoradiographic techniques to determine whether cells containing TH (a) were present in pancreas throughout pre- and postnatal development, (b) were localized to a specific region of the gland, (c) contained insulin at any time, and (d) proliferated. We found that TH cells were present in pancreas throughout life. In embryos, cells containing TH localized only along the pancreatic duct, also contained either glucagon or insulin, and were able to proliferate. In contrast, after birth, the pancreatic duct contained no TH cells. Cells containing TH in postnatal and adult mice also differed from embryonic TH cells in that they were found in all islets, contained insulin but not glucagon, and did not synthesize DNA, and hence did not proliferate. These findings suggest that progenitor cells that contain catecholamines and are present in the pancreatic duct give rise to glucagon and insulin cells of adult islets. They also indicate that the TH insulin cells of postnatal and adult mice are not stem cells but are postmitotic cells that appear in the islets after birth. PMID- 2884154 TI - Comparison of the effects of elevated K+ ions and muscle-conditioned medium on the neurotransmitter phenotype of cultured sympathetic neurons. AB - Neuronal depolarization and culture media conditioned by certain nonneuronal cells (CM) are known to exert opposite effects on the expression of cholinergic and noradrenergic traits in cultured rat sympathetic neurons. We have compared their effects on the developments of choline acetyltransferase (CAT), tyrosine hydroxylase (TOH), dopa decarboxylase (AADC) and acetylcholinesterase (AcChE) in these cultures. A macromolecular factor which was partially purified from CM increased CAT development in a dose-dependent manner and depressed the development of TOH and AADC by 5- to 10-fold. In the presence of intermediate concentrations of this partially purified factor, both CAT and catecholamine synthesizing enzymes developed to high levels, whereas high concentrations caused a long-lasting, but not total, impairment of TOH development. The effects of CM on both CAT and AADC activities resulted from variations in the number of immunotitratable enzyme molecules. Conversely, K+ ions (30-40 mM) depressed the development of CAT by 90% and stimulated TOH development 2.5-fold. Cultures grown with CM in high K+ medium had similar CAT and TOH activities as compared to those cultures grown without CM in low K+ medium suggesting that CM and K+ ions had antagonistic effects on the expression of these enzymes. However, K+ ions did not affect the development of AADC in these cultures. CM suppressed in a reversible manner the development of the 16 S form of AcChE. In the presence of 40 mM K+, the rate of development of AcChE was reduced. In particular, the development of 16 S AcChE was strikingly impaired, although not totally suppressed. The effect of elevated K+ ions on the percentage of 16 S AcChE was rapidly reversible. It is concluded that CM and elevated K+ ions have antagonistic effects on CAT and TOH, but not on AADC development; AcChE, in particular its asymmetric 16 S form, is regulated independently of the cholinergic/noradrenergic status of sympathetic neurons. PMID- 2884155 TI - Oocyte-specific expression and developmental regulation of ZP3, the sperm receptor of the mouse zona pellucida. AB - The mouse zona pellucida is composed of three sulfated glycoproteins, encoded by the oocyte genome, that have important biological functions in preimplantation development. One of the zona gene products, ZP3, functions as the sperm receptor at fertilization. Our present data demonstrate that the ZP3 gene is transcribed in oocytes where its expression is developmentally regulated. Resting primordial oocytes do not express ZP3 mRNA, but these transcripts rapidly accumulate in growing oocytes so that they represent 0.1-0.2% of the total poly(A+) RNA. As oocytes complete their growth and undergo meiotic maturation, the abundance of ZP3 transcripts falls off dramatically; ovulated eggs contain less than 15% of peak levels. The oocyte-specific accumulation of ZP3 transcripts serves as an attractive system for further studies of factors that modulate developmentally regulated genes during mammalian oogenesis. PMID- 2884156 TI - Gene amplification: the Chinese hamster glutamine synthetase gene. AB - The glutamine analogue, methionine sulphoximine, has been used to develop Chinese hamster ovary cell lines which overproduce the enzyme glutamine synthetase. Southern and Northern blot hybridization studies showed that this overproduction is due to gene amplification of a region of DNA containing the glutamine synthesis gene coding sequences, with a corresponding increase in glutamine synthetase mRNA and protein. This amplification has increased the glutamine synthetase gene copy number to approximately 1000 copies per cell. Genomic DNA sequences from the amplified region have been cloned and the structure of the glutamine synthetase gene within this region is being analysed. PMID- 2884157 TI - Basal and meal-induced somatostatin-like immunoreactivity in healthy subjects and in IDDM and totally pancreatectomized patients. Effects of acute blood glucose normalization. AB - We investigated the impact of blood glucose normalization on plasma levels of somatostatin-like immunoreactivity (SLI) in subjects with C-peptide-negative insulin-dependent diabetes mellitus (IDDM) and in totally pancreatectomized patients. Patients were studied during hyperglycemia and during normoglycemia, which was attained by Biostator-directed feedback insulin infusion. The experiments were performed in the fasted state and after a standardized breakfast. In IDDM (n = 6), basal levels of SLI were significantly higher than in nondiabetic subjects (n = 18). In IDDM, normalization of hyperglycemia was followed by a 40% decline in basal SLI (P less than .05). After the meal, SLI increased to the same absolute levels with or without feedback insulin treatment; however, the incremental response was 60% higher during feedback insulin treatment (P less than .05). Treatment also suppressed fasting and postprandial levels of glucagon, whereas gastric inhibitory polypeptide (GIP) levels were unaltered. In four pancreatectomized patients, normoglycemia tended to lower plasma levels of SLI by 50% (P less than .1). After breakfast, an SLI response was noted during normoglycemia, whereas no significant effect of the meal was seen during hyperglycemia. We conclude that in IDDM and in totally pancreatectomized patients, administration of insulin with subsequent normalization of blood glucose is accompanied by a decline in plasma levels of SLI in the fasted state, whereas the apparent response to a meal is enhanced. These effects on plasma levels of SLI probably reflect to a major extent release of somatostatin from the gastrointestinal tract. PMID- 2884158 TI - Hypersecretion of gastric somatostatin in spontaneously diabetic BB rats. AB - We previously reported that the BB diabetic rat is characterized by a reduction in pancreatic immunoreactive somatostatin (SLI) content, delta-cell mass, and delta-cell secretory reserve. Despite this, portal plasma SLI levels are elevated in diabetic animals and normalized by insulin therapy. These findings comprise indirect evidence for SLI hypersecretion by the gut in untreated BB rats. This study was undertaken with isolated stomach perfusions to investigate directly the secretory status of gastric delta-cells in this diabetic model. Isolated stomachs of three groups of insulin-treated diabetic, untreated diabetic, and nondiabetic control rats were perfused in situ under basal and glucagon-stimulated (5 nM) conditions. Untreated diabetic BB rats exhibited significant enhancement of basal and glucagon-stimulated gastric SLI release. Insulin treatment reduced gastric SLI release to significantly subnormal levels. More than 95% of basal and stimulated SLI released in diabetic BB and normal control rats coeluted with synthetic somatostatin-14 on Sephadex G-50 columns. We conclude that basal and stimulated gastric SLI release is increased in untreated BB rats and is suppressed with insulin therapy, gastric delta-cell hyperfunction accounts for portal vein hypersomatostatinemia characteristic of untreated diabetic BB rats, and somatostatin-14 is the main molecular form of SLI released from normal and diabetic stomachs. PMID- 2884160 TI - [Endocrine and humoral aspects of the physiology of sports]. PMID- 2884159 TI - Importance of glucagon in the control of futile cycling as studied in alloxan diabetic dogs. AB - In order to determine the role of glucagon in futile or substrate cycling in diabetes, we measured tracer determined glucose kinetics during a combined infusion of 2-3H-glucose (total glucose production) and 6-3H-glucose (glucose production) in six alloxan-diabetic dogs. The animals received either a 420 min infusion of (1) somatostatin alone (0.3 microgram X kg-1 X min-1), (2) somatostatin with insulin replacement (100 microU X kg-1 X min-1) or (3) glucagon (6 ng X kg-1 X min-1) together with somatostatin and transient insulin replacement. When somatostatin was given alone, plasma glucagon (p less than 0.004) and insulin (p less than 0.0001) were suppressed. Glucose production and disappearance and plasma glucose concentrations fell (p less than 0.0001), but the metabolic clearance of glucose did not change significantly. In the basal state, futile cycling comprised 29 +/- 4%, 33 +/- 4% and 33 +/- 3% of total glucose production in the three groups of studies, which is high compared to normal dogs. The absolute rate of futile cycling fell slightly but significantly from 10.0 +/- 1.7 to 8.3 +/- 1.7 mumol X kg X -1 min-1 (p less than 0.0008). When insulin replacement was given during somatostatin infusion to correct for the small somatostatin-induced insulin suppression, there were similar changes in plasma glucagon, glucose concentrations and glucose kinetics as seen during the infusion of somatostatin alone. Futile cycling decreased to a slightly greater extent from 12.8 +/- 2.8 to 9.5 +/- 1.7 mumol X kg-1 X min.-1 (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884161 TI - [Tricyclic structure of drugs and hepatotoxicity]. PMID- 2884162 TI - [New salazosulfapyridine derivatives. Progress in the treatment of chronic inflammatory diseases of the intestines?]. PMID- 2884163 TI - A comparative immunocytochemical study of the gastro-entero-pancreatic (GEP) endocrine system in a stomachless and a stomach-containing teleost. AB - The gastro-entero-pancreatic (GEP) endocrine system of a stomach-containing and of a stomachless teleost, Sparus auratus and Barbus conchonius, respectively, are studied immunocytochemically using different antisera against mammalian hormones. Insulin-, glucagon-, somatostatin-, and pancreatic polypeptide (PP) immunoreactive cells are identified in the endocrine pancreas of both species. Only the distribution of PP-immunoreactive cells differed strongly; in the principal islet of both fishes, few PP-immunoreactive cells are present, whereas in the smaller ones many of them are observed in S. auratus and none in B. conchonius. In the digestive tract of S. auratus 10 endocrine cell types can be distinguished: neurotensin-, secretin-, serotonin-, somatostatin-, and two types of substance P-immunoreactive cells exclusively in the stomach, and C-t gastrin/CCK-, glucagon-, Met-enkephalin-, PP-, and only one type of substance P immunoreactive cells in the intestinal epithelium. With the exception of substance P-immunoreactive cells, the other four intestinal endocrine cells, as well as an unspecific immunoreactive cell, can also be found in B. conchonius. Coexistence of glucagon- and PP-like immunoreactivity is observed in the pancreas of S. auratus and in the gut of B. conchonius. Pancreatic and gut endocrine cells showing only PP- or glucagon-like immunoreactivity are found, too. PMID- 2884164 TI - Molecular markers for the agouti coat color locus of the mouse. AB - The agouti (a) coat color locus of the mouse acts within the microenvironment of the hair follicle to control the relative amount and distribution of yellow and black pigment in the coat hairs. Over 18 different mutations with complex dominance relationships have been described at this locus. The lethal yellow (Ay) mutation is the top dominant of this series and is uniquely associated with an endogenous provirus, Emv-15, in three highly inbred strains. However, we report here that it is unlikely that the provirus itself causes the Ay-associated alteration in coat color, since one strain of mice (YBR-Ay/a) lacks the provirus but still retains a yellow coat color. Using single-copy mouse DNA sequences from the regions flanking Emv-15 we have detected three patterns of restriction fragment length polymorphisms (RFLPs) within this region that can be used as molecular markers for different agouti locus alleles: a wild-type agouti (A) pattern, a pattern which generally cosegregates with the nonagouti (a) mutation, and a pattern which is specific to Emv-15. We have used these RFLPs and a panel of 28 recombinant inbred mouse strains to determine the genetic linkage of these sequences with the agouti locus and have found complete concordance between the two (95% confidence limit of 0.00 to 3.79 centimorgans). We have also physically mapped these sequences by in situ hybridization to band H1 of chromosome 2, thus directly confirming previous assignments of the location of the agouti locus. PMID- 2884165 TI - Neuroleptic malignant syndrome as a possible postoperative complication: a case report. AB - Neuroleptic therapy for postoperative agitation in a mentally retarded schizophrenic patient is described. Clinical features consistent with neuroleptic malignant syndrome (NMS) developed. NMS is a dangerous, drug-induced complication of neuroleptic administrations that can be a differential diagnostic problem. Already often misdiagnosed, this syndrome is especially likely to be unrecognized in nonpsychiatric settings, and may occur postoperatively. Failure to recognize NMS may lead to reexposures to the offending agent, with potentially grave consequences. PMID- 2884166 TI - Inpatient treatment of the psychiatric patient with alcoholism. AB - Patients with both alcoholism and mental illness, or the one masquerading as the other, are very common and often puzzling and discouraging to clinicians. This article reviews several aspects of these problems: epidemiologic studies show that substantial proportions of mentally ill people suffer from alcoholism, and these disorders interlock in complex ways, each exacerbating the other. Many physicians feel uncomfortable working with alcoholic people, mostly because of poor training, and this impinges on difficulties of giving excellent care to these taxing patients. Complexities and resistances to interviewing obstruct evaluation. Interviewing and history taking techniques and the reason for them are discussed. The decision whether a patient needs medical or psychiatric hospitalization, alcoholism rehabilitation, or outpatient psychiatric or alcoholism treatment is reviewed along with the management and sequencing of treatment for primary and secondary alcoholism with concomitant psychosis, mania, depression, panic disorder, and adult attention deficit disorder. Clinical intervention and referral for the patient on a medical or surgical floor who may have alcoholism is discussed. Two special clinical problems, the differential diagnosis of postdetoxification depression and the risks of using alcohol cross tolerant drugs, are also reviewed. PMID- 2884167 TI - Ipecac abuse: a serious complication in bulimia. AB - Ipecac abuse among bulimics is being increasingly reported. The case presented is a 19-year-old female with significant eating-related problems, including frequent binges and daily use of ipecac to induce vomiting. Medical evaluation revealed significant muscle weakness, cardiac impairment, and altered levels of serum enzymes. The physical debilitation caused by the ipecac use dissipated following apparent discontinuation of ipecac ingestion. The symptom presentation and management problems in this case are discussed to alert clinicians involved in consultation about ipecac abuse. PMID- 2884168 TI - Isolation and characterization of DNA probes from the short arm of the human X chromosome that detect restriction fragment length polymorphisms. AB - We have isolated 30 X chromosome specific probes from a flow-sorted library enriched for the human X chromosome. Hybridization to somatic cell hybrids containing different regions of the X chromosome localized nine of these probes to Xp. After testing 185 probe-enzyme combinations, three of the Xp probes were found to detect restriction fragment length polymorphisms. PMID- 2884169 TI - The construction of a cloning vector designed for gene replacement in Bordetella pertussis. AB - We report here the construction of a plasmid cloning vector, pRTP1, designed to facilitate exchange of cloned and chromosomal alleles of the human bacterial pathogen Bordetella pertussis. pRTP1 provides the ability to successively select two homologous recombination events within the cloned sequences. The first is by selection for maintenance of the ampicillin-resistance gene on the plasmid which is unable to replicate autonomously after transfer via conjugation. The second selection, via streptomycin (Sm) selection, is against the maintenance of vector sequences which contain a gene encoding the Sm-sensitive allele of the gene for ribosomal protein S12 thus rendering an otherwise Sm-resistant strain Sm sensitive. We demonstrate the use of this vector to introduce an unmarked mutation, constructed in vitro, into the chromosomal locus encoding pertussis toxin. PMID- 2884171 TI - Inhibition of meal stimulated gastric acid secretion by an octapeptide somatostatin analogue SMS 201-995. AB - A dose response study of the effect of an octapeptide somatostatin analogue, SMS 201-995, on meal stimulated gastric acid secretion was carried out in 12 healthy volunteers. Infusion of SMS 201-995 in a dose of 50 pmol/kg/h almost completely abolished the acid response to the meal. Pl-gastrin was significantly decreased during infusion of 10 pmol/kg/h of SMS 201-995 and insulin was significantly inhibited during infusion of 50 pmol/kg/h. SMS 201-995 in a dose of 50 pmol/kg/h inhibited basal and submaximal pentagastrin stimulated acid secretion by 77% and 84% respectively (p less than 0.01). On a molar basis SMS 201-995 is substantially more potent than natural somatostatin in inhibiting gastric acid secretion. PMID- 2884170 TI - Nucleotide sequence of the rice cytochrome f gene and the presence of sequence variation near this gene. AB - The rice (Oryza sativa L. var. Labelle) chloroplast (cp) gene encoding cytochrome f has been isolated and sequenced. The coding region of this rice gene displays 95.1%, 85.3% and 85.2% nucleotide sequence homology with that of wheat, pea and spinach, respectively. To examine the cpDNA sequence variation in rice, cpDNA from Labelle and its parents, Belle Patna and Dawn was compared. Using the cytochrome f gene as the probe for hybridization, we found several differences in the size and number of restriction fragments in the cp genome of three rice varieties. An additional restriction fragment found in the Belle Patna cp suggests that this cp genome is either heterogeneous or contains two copies of cytochrome f gene per cpDNA. PMID- 2884173 TI - Evidence of Negro origin of HbC in Sicily. PMID- 2884172 TI - [Treatment and monitoring of patients with signs of premature labor up to the 32d week of pregnancy]. PMID- 2884175 TI - [Venous diseases--an underestimated hazard]. PMID- 2884176 TI - [Possibilities and limits in the treatment of uncomplicated diarrhea]. PMID- 2884174 TI - [Pharmacological studies on Y-8894. (V) Effect on learning and memory in intact and experimentally amnesic rats]. AB - The effects of Y-8894 on learning and memory were studied using the pole climbing avoidance (PCA) response in intact and experimentally induced amnesic rats. The following results were obtained: A single administration of Y-8894 (2.5 mg/kg, i.p.) to experimentally induced amnesic rats significantly antagonized the decrease in the mean number of PCA responses induced by an electroconvulsive shock (ECS). At a higher dose (10 mg/kg, i.p.), however, this effect was reduced. Repeated administration of Y-8894 (5 mg/kg, i.p.) significantly antagonized the facilitation of the extinction of the PCA response induced by exposure to CO2. Repeated administration of Y-8894 (2.5 mg/kg, i.p.) significantly facilitated the learning of the PCA response in intact rats. At a higher dose (5 mg/kg, i.p.), however, this effect was reduced. A single administration of Y-8894 (5 mg/kg, i.p. and 25 mg/kg, p.o.) significantly delayed the extinction of the PCA response in intact rats. These results suggest that Y-8894 has an ameliorative and facilitative effect on learning and memory in experimentally induced amnesic and intact rats. PMID- 2884177 TI - [New guidelines in the treatment of chronic cardiac insufficiency]. PMID- 2884178 TI - [Nisoldipin: a vasoselective calcium antagonist]. PMID- 2884179 TI - Diabetogenic action of GH and cortisol in insulin-dependent diabetes mellitus. Aspects of the mechanisms behind the Somogyi phenomenon. AB - The effect on glucose homeostasis of a transient elevation of plasma growth hormone (GH) and cortisol was studied over 6 h in 14 male patients with insulin dependent diabetes mellitus (IDDM) by using an i.v. somatostatin (100 micrograms/h) - insulin (0.4 mU/kg/min) glucose (3 mg/kg/min) - infusion test (SIGIT). GH (20 mU/kg) was given as a 60 min i.v. infusion during the initial SIGIT period raising the plasma GH level to about 40 micrograms/l, and returning to low basal within 3 h. ACTH (0.1 mg) was given as an i.v. bolus injection at the start of the SIGIT, resulting in plasma cortisol peak values of about 900 nmol/l within 2-3 h. GH raised blood glucose after a lag of 4 h while ACTH alone had no effect. However, ACTH added to GH enhanced the diabetogenic effect of GH. It is concluded that an episodic increase in circulating GH-cortisol, resembling the responses of these hormones to an insulin-induced hypoglycemia, exerts a diabetogenic effect in IDDM-patients not deprived of insulin. While GH is essential in this respect the diabetogenic effect of cortisol is evident only in conjunction with GH. PMID- 2884180 TI - Isoprenaline-induced myocardial damage & the cardioprotective action of some beta adrenoceptor blockers in albino rats. PMID- 2884181 TI - Spoke-wheel injuries. PMID- 2884182 TI - An approach to monitoring mutation rates using restriction fragment lengths. AB - Monitoring background mutation rates in normal populations, elevated rates in exposed populations and unusual rates in test systems exposed to mutagens and carcinogens remains an unresolved problem. To date, efforts have focused on measurement of mutation rates by searching for protein sequences that appear in children but were not present in their parents. An initial study to measure mutation rates by using recombinant DNA technology was carried out in Alta, Utah, in 1984, and the results are summarized here. The purpose of this paper is to explore in greater detail the use of restriction fragment lengths for monitoring mutation rates. The report of the meeting at Alta was sceptical about the practicality of this approach. The conclusion of this paper is that it is indeed a practical approach, and details are given of a method for realizing a functional system. PMID- 2884183 TI - Screening for carcinoma-in-situ of the testis. AB - Germ cell neoplasia detected at the preinvasive stage of carcinoma-in-situ (CIS) can be cured by orchidectomy or by localized irradiation of the testis. Therefore, screening for carcinoma-in-situ of the testis has been applied to groups of individuals known to have an increased risk of testicular cancer. A high (5.5%) incidence of CIS was found in the contralateral testis of men with a unilateral cancer of the testis. An increased incidence of CIS was also found among men with a history of cryptorchidism. We recommend routine screening for CIS of the testis in both groups of men. The role of screening for CIS among subfertile men remains to be elucidated. PMID- 2884184 TI - Experience of screening for carcinoma-in-situ of the testis among young men with surgically corrected maldescended testes. AB - One hundred and twelve young men with maldescended testes which had been surgically corrected were examined for premalignant/malignant changes in the testes. Bilateral testicular biopsies were made in ninety-four patients. Three had carcinoma-in-situ of the testis in the biopsy. Invasive tumour of seminomatous type was found in two of these testes after orchidectomy had been performed. No correlation was found with testicular localization pre- or postoperatively, with testicular volume or with tumour markers. PMID- 2884185 TI - Ultrasound in detection of early neoplasia of the testis. AB - Testicular ultrasound scanning was performed in 192 men with a history of cryptorchidism. The ultrasonic tissue pattern was evaluated and each testis was accordingly given a score on a scale from 1 to 4, 1 representing the normal uniform pattern and 4 being a very irregular pattern. Testicular biopsy of the previously maldescended testicle(s) was carried out in 143 of the scanned men and from two contralateral testicles where the score 4 was given at the ultrasound examination. Two biopsies showed carcinoma-in-situ pattern. Both were found among testes with a very irregular echo pattern. This pattern was found in only 3.2% of all scanned testes. PMID- 2884186 TI - Testicular biopsy as an outpatient procedure in screening for carcinoma-in-situ: complications and the patient's acceptance. AB - Testicular biopsy has been performed as a simple outpatient procedure to facilitate screening purposes. The target population was men aged 20-30 years with previous cryptorchidism, and the aim of the study was to discover carcinoma in-situ. When results from the first 209 consecutive males were assessed, very few and minor complications were encountered. Only three patients needed hospitalization for drainage of pus from the wound. The effects of the procedure as experienced by the patients were evaluated by a questionnaire. 72% of the patients found the method acceptable. The advantages were the patients' minimal absence from their jobs, and the low consumption of resources. PMID- 2884187 TI - The clinical significance of intrinsic sympathomimetic activity. PMID- 2884188 TI - Beta-blockade in acute myocardial infarction: is Swan-Ganz catheterization required before treatment? AB - Beta-blockade is used increasingly in early acute myocardial infarction (AMI) but may cause congestive heart failure (CHF). It is not known whether Swan-Ganz catheterization is necessary before beta-blockade in AMI. We made a retrospective analysis of 213 patients who underwent Swan-Ganz catheterization within 24 hours of AMI and compared precatheter CHF signs (dyspnoea, lung crepitations and x-ray appearance) with initial pulmonary artery wedge pressure (PAWP). One hundred nine of these patients received beta-blockade after catheterization, 31 did not tolerate beta-blockade. Absence of clinical CHF signs predicted a normal PAWP (less than or equal to 18 mmHg) in 86% of patients (42 of 49) and considerable safety in giving beta-blockade. Beta-blockade had to be stopped because of PAWP increase (greater than 5 mmHg) in 25 of 74 patients with CHF signs vs. 3 of 35 patients without CHF signs (p less than 0.005), and in 9 of 15 patients with high PAWP vs. 19 of 91 patients with normal PAWP (p less than 0.01). Only 2/28 patients (7%) intolerant to beta-blockade had a high PAWP but no clinical CHF. In conclusion hemodynamic intolerance to beta-blockade could have been predicted clinically without prior Swan-Ganz catheterization in 25/28 patients. Patients with CHF signs require catheterization if beta-blockade therapy is to be considered. PMID- 2884189 TI - Nabumetone (BRL 14777) presystemic elimination and disposition in patients with liver impairments. AB - The effect of presystemic elimination of nabumetone disposition was evaluated in 6 cirrhotic patients after oral administration of a single dose of 1000 mg of the drug. The data revealed the major role of hepatic metabolism in the removal of the drug from the body. The relatively high values of hepatic plasma excretion ratio (= 0.60 +/- 0.04) and of the total intrinsic clearance (= 90.74 +/- 15.87 l/h) places nabumetone between drugs with intermediate properties; clearance being partly dependent on plasma (blood) flow rate and on the hepatic metabolism whose systemic availability was 32% of the dose. Very good coincidence was obtained when ranging patients according to morphological evaluation of liver impairments was compared to the values of nabumetone disposition parameters. There was a statistically significant positive correlation (r = 0.831, p less than 0.05) between the fraction of the dose reaching the systemic circulation, f, and the gamma-GT "normalization index" (i.e., ratio between the observed decrease of serum gamma-glutamyl transpeptidase activity and the pretreatment difference from the upper normal value). A definite interpretation of the data cannot be provided until more knowledge about the effect of 6-mO-2-naphthylacetic acid on nabumetone metabolism is available. PMID- 2884190 TI - Effect of mifentidine, a new H2-antagonist, on pentagastrin-stimulated acid secretion in healthy subjects. AB - The purpose of this study is to investigate the effects of a single oral dose of 10 mg of mifentidine, a new H2-receptor antagonist, on unstimulated and pentagastrin-stimulated gastric acid secretion in healthy subjects. The study was carried out in a double-blind randomized, placebo controlled, cross-over design. Ten subjects were given both placebo and active drug, with a wash-out period of at least 3 days. Unstimulated acid secretion was measured in the period between 1 and 1.5 h after drug administration. Immediately thereafter, 2 micrograms/kg/h of pentagastrin was infused intravenously and pentagastrin-stimulated gastric acid secretion was determined for two subsequent hours. The volume of gastric secretion was significantly less after mifentidine than after placebo during the pentagastrin-stimulated period. Acid output was inhibited during unstimulated and pentagastrin-stimulated secretion by mifentidine by 45% and 39% of the placebo values, respectively. No adverse clinical or laboratory effects were noted during the study. The results of this study indicate that mifentidine, given as a single oral dose of 10 mg, inhibits effectively unstimulated and pentagastrin-stimulated acid secretion in healthy subjects. PMID- 2884191 TI - The excretion of renal enzymes during rest and exercise: a double-blind comparison between placebo and penbutolol. AB - A double-blind cross-over study was carried out in five healthy male volunteers to investigate the renal tolerance of 40 mg penbutolol, a receptor-specific beta blocking agent, during exercise and to compare its effects with a placebo. The effects of exercise were compared with a resting state after a medication on the placebo. Urine was collected in fractions for seven hours on each trial day. The urine volume and the excretion of alanine aminopeptidase (AAP), N-acetyl-beta-D glucosaminidase (NAG) and gamma glutamyltransferase (GGT) per fraction were determined. The findings for the kidney enzymes AAP, NAG and GGT show that the renal tolerance of penbutolol was good. Physical exercise per se did not cause any increase in the excretion of the above-mentioned enzymes. Slight diurnal variation was seen in the excretion of the renal enzymes after both the placebo and penbutolol. PMID- 2884192 TI - Prevention and early diagnosis of cancer in the rectal stump of ulcerative colitis patients after colectomy and topical treatment. AB - Ulcerative colitis with malignant degeneration and dysplasia can be a precancerous lesion. Therefore, it is necessary to prevent or, at least to diagnose as early as possible any development toward neoplasia in the colon or rectum of the colitis patients. The only reliable guide for a risk of malignant tissue degeneration is dysplasia of the mucosa. A group of 31 patients was studied after total colectomy with ileorectal anastomosis and subsequent topical treatment with enemas containing sulphasalazine and corticosteroids. Two of these patients had mild rectal dysplasia before surgery, seen in a biopsy specimen obtained endoscopically. All the patients were followed for a long time after surgery, with endoscopy and microscopic and ultrastructural observation of rectal biopsy material taken from different sites in the mucosa, both from areas that looked dysplastic by endoscopy and from those that appeared normal. The two patients with presurgical dysplasia, when examined later, one 12 months and one 18 months after surgery, had no rectal dysplasia; the mucosal covering was moderately complete and the anastomosis was functioning. It is considered that to prevent development of cancer in the rectal stump, colectomy should always be followed by regular topical treatment and there should be a check-up at short intervals for early diagnosis of any premalignant areas that might develop. Regression of such lesion was observed to lesser degrees after continuous treatment with the topical medication. PMID- 2884193 TI - Changes in lymphocyte subsets after treatment with cyclophosphamide and during the development of contact sensitivity in the guinea pig. AB - Changes in lymphocyte subpopulations were investigated in guinea pig lymph nodes during the development of contact sensitivity to 2,4-dinitrofluorobenzene (DNFB) and following the injection of cyclophosphamide (CY; 300 mg/kg) using a panel of monoclonal antibodies against guinea pig lymphocyte surface markers. Application of a sensitizing dose of DNFB to the ear resulted in a significant increase in the number of cells recovered from the draining auricular and cervical lymph nodes, 4 and 6 days post sensitization. A significant increase in the number of cells in the contralateral cervical node was found at day 6 but not at day 4. At 4 days postsensitization the proportions of Ia positive lymphocytes were higher than those of immunoglobulin positive B cells in the draining auricular and cervical node and the contralateral cervical lymph nodes suggesting T-cell "activation". Four and six days after sensitization there were no significant changes in the proportions of Pan T and T suppressor/cytotoxic (Ts/c) positive lymphocytes in the draining auricular and cervical lymph nodes. Although contact sensitivity is "classically" a T-cell mediated phenomenon there was a significant increase in the proportion of B cells found in the draining auricular node 4 days after sensitization as compared to the "normal" auricular node. 1, 2, 3 and 7 days after injection of CY there was a significant depletion in the proportion of B-lymphocytes in the cervical lymph node. This effect was maximal between 2 and 3 days after CY and was paralleled by an increase in the proportion of Pan T positive cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884194 TI - Indications for treatment. PMID- 2884195 TI - Steroid potentiation of beta-adrenergic-sensitive adenylate cyclase in rabbit ciliary processes. AB - Dexamethasone (3.3 X 10(-8) M) potentiated 1-isoproterenol-stimulated adenylated cyclase activity in vitro in rabbit ciliary process epithelial membrane preparations. The ka for isoproterenol stimulation of the cyclase was 5 X 10(-7) M in control membranes, 2.5 X 10(-9) M in membranes preincubated with dexamethasone, and 6 X 10(-8) M with corticosterone. No change was observed in basal adenylate cyclase activity. Changes in enzyme activity at maximally stimulating levels of isoproterenol were not consistently different. Dose response to corticosterone in the presence of 10(-7) M 1-isoproterenol shows maximum effect at 6.6 X 10(-8) M corticosterone. PMID- 2884196 TI - Induction of ovulation. Gonadotrophin therapy. PMID- 2884197 TI - Effect of somatostatin in controlling bleeding from esophageal varices. AB - A multicenter double-blind clinical trial was undertaken to evaluate the efficacy of a short-term somatostatin treatment versus a short-term vasopressin treatment on acute hemorrhage from esophageal varices in patients with liver cirrhosis and portal hypertension. Forty-nine patients with massive hemorrhage and endoscopic diagnosis of bleeding esophageal varices completed the study. Patients were randomly assigned to somatostatin treatment (24 patients: 250 micrograms/hr i.v. for 48 hrs) or vasopressin treatment (25 patients: 0.1 U/min i.v. for 48 hrs). The Sengstaken-Blakemore tube was utilized, when needed, for a six hour period. In case of failure the patients were crossed-over to the other treatment. Patients in whom the bleeding stopped at 48 hrs, were randomly assigned to somatostatin (250 micrograms/hr i.v.) or placebo for seven days. Bleeding stopped in 68% of patients treated with somatostatin and in 28% of patients treated with vasopressin (p less than 0.0013). Mortality rate was lower, but not significantly so, in the somatostatin group compared to the vasopressin group. No differences were noted between somatostatin and placebo in preventing bleeding recurrences. These data suggest that somatostatin, when combined if necessary with a 6 hour period of balloon tamponade, is more effective than vasopressin at low doses in controlling severe hemorrhage from esophageal varices in patients with liver cirrhosis and portal hypertension. A clinical use of somatostatin seems to be indicated in these patients. PMID- 2884198 TI - Anti-carcinogenic effects of a serine protease inhibitor (FOY-305) through the suppression of neutral serine protease activity during chemical hepatocarcinogenesis in rats. PMID- 2884199 TI - Arylsulphatase activity and cerebroside sulphates in the frog oviduct during the reproductive cycle. AB - The presence of arylsulphatase A and cerebroside sulphates in different tracts of Rana esculenta oviduct during different phases of the reproductive cycle were investigated by histochemical and biochemical procedures. The results indicate that enzyme activity shows seasonal fluctuations connected with the phase of the sexual cycle. The concentrations of cerebroside sulphates (the natural substrates of arylsulphatase A) is related to the activity of this hydrolytic enzyme. The role of arylsulphatase A activity in regulating the substrate concentration, and particularly that of sulphatides, is discussed. PMID- 2884202 TI - Immune systems and neuroendocrines. PMID- 2884203 TI - External neutron beam therapy. PMID- 2884201 TI - Comparison of DR beta 1 alleles from diabetic and normal individuals. AB - Insulin-dependent diabetes (IDD) is positively associated with HLA-D proteins. A critical question is whether or not sequence differences within the HLA-D coding region are the same or different in diabetics and normal individuals of the same haplotype. We have isolated both DR beta 1 alleles from a Dw4/LD MN2 cDNA library and compared them to DR beta 1 genes isolated from normal individuals of the same Dw phenotype. We found no nucleotide differences in the coding region between the normal and diabetic alleles of DR beta 1 suggesting to us that DNA differences other than the DR beta 1 coding region may account for the observed association of HLA-D and diabetes. PMID- 2884200 TI - Catecholamine-synthesizing enzymes in the rat pituitary. An immunohistochemical study. AB - The catecholamine-containing nerve fibers of the rat pituitary were studied by immunohistochemical demonstration of the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT). Immunohistochemical demonstration of TH confirms earlier catecholamine fluorescence histochemical studies showing a fine network of varicose fibers in both the intermediate and the neural lobe, with the most dense aggregation of fibers at the border between the lobes. DBH-immunoreactive fibers were much less in number, and confined to the neural lobe, where both vascular and parenchymal fibers were seen. With the antibody to PNMT bright staining was seen in all the glandular cells of the intermediate lobe, while the neural lobe was negative. No immunoreactive structures were observed in the anterior lobe. Functionally the study confirms the presence of an extensive dopaminergic innervation of the neurointermediate lobe, giving an anatomical basis for the tonic inhibitory action of dopamine on the intermediate lobe cells and for recent observations attributing dopamine a local regulatory function also in the neural lobe. In addition to vascular noradrenaline-containing fibers as described earlier the study shows parenchymal DBH-immunoreactive fibers in the neural lobe, suggesting a local role for noradrenaline in this lobe. The nature of the cellular PNMT-immunoreactivity in the intermediate lobe remains to be established. The cellular localization of the PNMT-immunoreactivity was distinctly different than that of the alpha-MSH-immunoreactivity within the intermediate lobe cells and reserpine treatment did not affect the PNMT immunoreactivity although it induced a heterogeneous depletion of alpha-MSH and related peptides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884204 TI - Elder abuse: the physician's role in identification and prevention. PMID- 2884205 TI - Transmission of adult T-cell leukemia retrovirus (HTLV-I) from mother to child: comparison of bottle- with breast-fed babies. AB - HTLV-I is commonly believed to be transmitted from HTLV-I seropositive mothers to infants via breast milk. In 11 of 24 breast-fed infants born to HTLV-I seropositive mothers, HTLV-I antigen-positive cells were detected in peripheral blood samples obtained 12 months after birth. In sharp contrast, they were detected in only one of 11 bottle-fed infants of HTLV-I seropositive mothers. Thus bottle-feeding appears to be an effective method to avoid HTLV-I transmission from HTLV-I seropositive mothers to infants. PMID- 2884206 TI - Evaluation of the safety of blood products with respect to human immunodeficiency virus infection by using an HTLV-I-infected cell line (SKT-1B). AB - Human immunodeficiency virus (HIV), the etiologic agent of acquired immunodeficiency syndrome (AIDS), was rapidly cytopathic to SKT-1B, a cell line established from a patient with adult T cell leukemia, in vitro. This cytopathic effect was preceded by the expression of HIV antigen, defined with a monoclonal antibody (mAb) specific for the core protein (p24) of HIV. SKT-1B is highly susceptible to HIV as compared with MT-2 and H9 cells. HIV is known to be transmitted via blood products, and thus we examined whether or not currently used procedures for manufacturing blood products are safe by using SKT-1B. Lyophilized HIV was heated at 65 degrees for time periods in the range of 10 min to 48 hr, and the infectivity was examined. The results showed that heating at 65 degrees for less than 2 hr was not sufficient to inactivate HIV, but the virus heated for 48 hr had no effect on SKT-1B. In addition, HIV completely lost its infectivity on sulfonation, which is commonly used to avoid anaphylactic shock on intravenous infusion of human immunoglobulins. These findings indicate that blood products manufactured by currently used procedures are probably safe with respect to HIV infection. PMID- 2884207 TI - Growth and adipose tissue metabolism in young pigs fed cimaterol with adequate or low dietary protein. AB - The beta-adrenergic agonist, cimaterol, was fed to young growing pigs to determine whether the carcass compositional changes observed in finishing pigs fed a beta-adrenergic agonist would be manifest in young animals. Furthermore, because cimaterol increased the deposition of lean mass in finishing pigs, it could have a protein sparing effect in young pigs that are rapidly accreting muscle mass and have a high dietary protein requirement. Pigs were fed cimaterol (at 0, .25 and .50 mg X kg-1 diet) and either an adequate (18%) or restricted (14%) protein diet from about 10 to 60 kg body weight. Pigs that were fed the 14 compared with 18% protein diet grew slower and ate less but had the same gain-to feed ratio. These pigs also had shorter carcasses, less lean muscle and more fat deposition (assessed by carcass measurements and carcass chemical composition) than pigs that received adequate protein. Plasma protein and albumin concentrations were greater and plasma cholesterol, triglyceride and fatty acid concentrations were lower in pigs fed high compared with low dietary protein. Dietary cimaterol had no effect on any of the growth or carcass variables or on adipose tissue metabolism. When fed the high protein diet, cimaterol-supplemented pigs had smaller livers and stomachs. Dietary cimaterol did not have any major detectable effects on these young pigs, nor was there any evidence for a protein sparing effect. PMID- 2884209 TI - Assembly of a chemically synthesized peptide of Escherichia coli type 1 fimbriae into fimbria-like antigenic structures. AB - Escherichia coli type 1 fimbriae are composed of subunits, each of which comprises 158 amino acids. We synthesized a copy of a 13-residue peptide, located near the NH2 terminus of the fimbrial subunit, that assumed some of the properties of type 1 fimbriae. At pH 5.5 the synthetic peptide autoassembled into fibrillar structures that resembled type 1 fimbriae except that they appeared less rigid and rodlike. A quaternary structure-specific monoclonal antibody against type 1 fimbriae recognized the synthetic peptide in the assembled but not the unassembled state. Furthermore, when the synthetic peptide was injected in its fimbrial conformation into rabbits, it evoked antibodies that reacted with type 1 fimbriae isolated from E. coli. PMID- 2884208 TI - Cloning and characterization of Saccharomyces cerevisiae genes that confer L methionine sulfoximine and tabtoxin resistance. AB - Pseudomonas tabaci produces a toxin, tabtoxin, that causes wildfire disease in tobacco. The primary target of tabtoxin is presumed to be glutamine synthetase. Some effects of tabtoxin in tobacco can be mimicked by methionine sulfoximine (MSO), a compound that is known to inactivate glutamine synthetase. To understand how organisms can be made resistant to tabtoxin and MSO, we used Saccharomyces cerevisiae. We demonstrate that yeast strains carrying the glutamine synthetase gene, GLN1, on a multicopy plasmid overproduced glutamine synthetase and showed increased drug resistance. These and other data indicate that glutamine synthetase is the primary target of tabtoxin and MSO in S. cerevisiae. We also isolated three S. cerevisiae DNA inserts of 2.1, 2.3, and 2.8 kilobases that conferred tabtoxin and MSO resistance when the inserts were present on a multicopy plasmid. These plasmids conferred resistance to MSO by blocking intracellular transport of the drug. Transport appeared to occur by one or more methionine permeases. Resistance to tabtoxin could also occur by blockage of intracellular transport, but the drug was transported by some permease other than a methionine permease. These drug resistance plasmids did not block transport of citrulline, indicating that they did not affect the general amino acid permease. PMID- 2884210 TI - Regulation of expression of glutamine synthetase in a symbiotic Nostoc strain associated with Anthoceros punctatus. AB - A characteristic of N2-fixing cyanobacteria in symbiotic associations appears to be release of N2-derived NH4+. The specific activity of the primary ammonium assimilating enzyme, glutamine synthetase (GS), was found to be three- to fourfold lower in Nostoc sp. strain 7801 grown in symbiotic association with the bryophyte Anthoceros punctatus than in free-living Nostoc sp. strain 7801. Quantitative immunological assays with antisera against GS purified from Nostoc sp. strain 7801 and from Escherichia coli indicated that similar amounts of the GS protein were present in symbiotic (50 micrograms mg-1) and free-living (68 micrograms mg-1) cultures. The conclusion from these experiments is that GS is regulated by a posttranslational mechanism in Anthoceros-associated Nostoc sp. strain 7801. However, the results of comparative catalytic and immunological experiments between N2- and NH4+-grown free-living Nostoc sp. strain 7801 implied control of GS synthesis. A correlation was not observed between the level of GS expression and the extent of symbiotic heterocyst differentiation in Nostoc sp. strain 7801 associated with A. punctatus. PMID- 2884212 TI - Characterization of transfer regions within the HII incompatibility group plasmid pHH1508a. AB - A circular map of the 208-kilobase IncHII plasmid pHH1508a was constructed by using the restriction endonucleases XbaI, XhoI, and NotI. Tn5 insertion mutagenesis showed that transfer genes were distributed widely over the plasmid map. Analysis of the deletion mutant pDT1178 indicated that genes required for conjugative pilus production are located in a 96.0-kilobase region of the plasmid. PMID- 2884213 TI - Akinesia and postpsychotic depression: a difficult differential diagnosis. AB - Detailed clinical case descriptions highlight the potential symptomatic overlap between the syndromes of akinesia and postpsychotic depression in neuroleptic treated patients. The cases demonstrate that both syndromes may resemble major depression phenomenologically. However, the syndromes are not identical in medication response. Thus, differential medication response may potentially be a useful tool in teasing apart the various postpsychotic depressionlike states in the course of schizophrenia or schizoaffective disorder. PMID- 2884211 TI - DNA replication by a DNA-membrane complex extracted from Bacillus subtilis: site of initiation in vitro and initiation potential of subcomplexes. AB - A DNA-membrane complex extracted from Bacillus subtilis was studied further as a model system for initiation of bacterial DNA replication in vitro. Of three subcomplexes purified from the crude complex by a combination of CsCl and sucrose gradient centrifugation, the synthetic capability of only one was inhibited significantly by streptovaricin, a known inhibitor of RNA primer formation. A selective enrichment in the level of this subcomplex was obtained by manipulating a thymine-requiring mutant. The synthetic capabilities of an enriched and nonenriched DNA-membrane complex were compared in the presence and absence of streptovaricin. Although the rate and extent of DNA synthesis per unit of protein were approximately the same in the absence of the antibiotic, there was a much greater inhibition of synthesis shown by the enriched complex in the presence of streptovaricin. Although the amount of DNA present in the putative initiation subcomplex was less than 0.3 to 0.4% of the total DNA present in the crude complex, such DNA, except for a few quantitative differences, was still representative of genomic DNA. Newly synthesized DNA hybridized to specific origin- and non-origin-derived restriction fragments of the B. subtilis genome. However, when an elongation inhibitor (ddCTP) was added, hybridization of such DNA to almost all of the nonorigin fragments disappeared or was reduced drastically, whereas origin region hybridization patterns remained strong. The highest level of hybridization in the origin region occurred with a BamHI (B7) restriction fragment of 5.6 kilobases that has been implicated by others as one site initiation in vivo (N. Ogasawara, M. Seiki, and H. Yoshikawa, Nature (London) 281:702-704, 1979; S. J. Seror-Laurent and G. Henckes, Proc. Natl. Acad. Sci. USA 82:3586-3590, 1985). PMID- 2884214 TI - Studies on nitrate reductase of Clostridium perfringens. IV. Identification of metals, molybdenum cofactor, and iron-sulfur cluster. AB - Nitrate reductase of Clostridium perfringens was purified by an improved method using immuno-affinity chromatography. The purified preparation contained Mo, Fe, and acid-labile sulfide; the Mo content was 1 mol per mol and the Fe 3.7 mol per mol of the enzyme. The inactive enzyme obtained from cells grown in the presence of tungstate did not hold Mo but contained 1 mol of W. The content of Fe was not increased. The presence of molybdenum cofactor in the nitrate reductase was indicated by the formation of molybdopterin form A in the oxidation of the enzyme by iodine and by the complementation of NADPH-nitrate reductase with the heart treated enzyme in the extract of Neurospora crassa nit-1. The Clostridium nitrate reductase had an absorption maximum at 279 nm and shoulders at 320, 380, 430, and 520 nm. This enzyme seems to contain an iron sulfur cluster since the reduced enzyme showed decreased absorption in visible region. The CD spectrum of the enzyme has a positive peak at 425 nm and negative ones at 310, 360, and 595 nm. It was compared with the CD spectrum of ferredoxin (2Fe-2S or 4Fe-4S cluster) and the nitrate reductase of Plectonema boryanum. PMID- 2884215 TI - Molecular cloning and sequencing of cDNA encoding goat pre alpha-lactalbumin. AB - In poly(A)+RNA extracted from a lactating goat mammary gland, mRNA of about 750 nucleotides was shown to encode pre alpha-lactalbumin by using in vitro translation and immunoprecipitation. From the total poly(A)+RNA, the cDNA library was constructed using the Escherichia coli plasmid pUC18; it was screened with the oligodeoxyribonucleotide probe corresponding to the amino acid sequence of Trp60-Gln65 of goat alpha-lactalbumin. A plasmid containing almost full-length cDNA of goat pre alpha-lactalbumin, pGLA-1, was identified. The cDNA insert of pGLA-1 comprises 727 base pairs and contains the signal peptide and mature protein sequence. PMID- 2884217 TI - Substrate specificity of acetyl coenzyme A synthetase. AB - Acetyl coenzyme A synthetase (EC 6.2.1.1) has been examined for its ability to accept various carboxylic acids as substrates in place of acetic acid. The activity of the enzyme with these substrates was monitored using a coupled enzyme assay and high pressure liquid chromatography (HPLC) analysis. Short chain carboxylic acids were found to be active including: propionic, acrylic, fluoroacetic, methacrylic, 3-chloropropionic, 3-bromopropionic, and propiolic. The kinetic parameters, Km and % Vmax of the carboxylic acid substrates, are reported and show that these acids are poorer substrates than acetic acid. Several of the acyl CoAs were synthesized on a preparative scale using enzyme catalysis, purified using preparative HPLC, and characterized using proton NMR spectroscopy. In the course of the NMR identification, a complete and fully resolved spectral assignment for all the protons of coenzyme A was made and is reported. The acyl-CoA analogs should be useful as substrate analogs and as potential affinity labels for enzymes that bind acetyl-CoA. PMID- 2884216 TI - On the role of subunit III in proton translocation in cytochrome c oxidase. AB - Mammalian mitochondrial cytochrome c oxidase catalyzes the transfer of electrons from ferrocytochrome c to molecular oxygen in the respiratory chain, while conserving the energy released during its electron transfer reactions by the vectorial movement of protons across the inner membrane of the mitochondrion. The protein domain that translocates the protons across the membrane is currently unknown. Recent research efforts have investigated the role of one of the transmembrane subunits of the enzyme (III, Mr 29,884) in the vectorial proton translocation reaction. The data that favor subunit III as integral in vectorial proton translocation as well as the data that support a more peripheral role for subunit III in proton translocation are reviewed. Possible experimental approaches to clarify this issue are presented and a general model discussed. PMID- 2884218 TI - Probing the catalytic subunit of the tonoplast H+-ATPase from oat roots. Binding of 7-chloro-4-nitrobenzo-2-oxa-1,3,-diazole to the 72-kilodalton polypeptide. AB - The purified tonoplast H+-ATPase from oat roots (Avena sativa L. var. Lang) consists of at least three different polypeptides with masses 72, 60, and 16 kDa. We have used covalent modifiers (inhibitors) and polyclonal antibodies to identify the catalytic subunit of the H+-pumping ATPase. The inactivation of ATPase activity by 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (Nbd-Cl, an adenine analog) was protected by MgATP or MgADP, and showed kinetic properties consistent with active site-directed inhibition. Under similar conditions, [14C]Nbd-Cl preferentially labeled the 72-kDa polypeptide of the purified ATPase. This binding was reduced by MgATP or 2' (3')-)O-(2,4,6-trinitrophenyl) ATP. Nbd-Cl probably modified cysteinyl--SH or tyrosyl--OH groups, as dithiothreitol reversed both ATPase inactivation and [14C]Nbd-Cl binding to the 72-kDa subunit. The finding that N-ethylmaleimide inhibition of ATPase activity was protectable by nucleotides is consistent with the idea of sulfhydryl groups in the ATP-binding site. Polyclonal antibody made to the 72-kDa polypeptide specifically reacted (Western blot) with a 72-kDa polypeptide from both tonoplast-enriched membranes and the purified tonoplast ATPase, but it did not cross-react with the mitochondrial or Escherichia coli F1-ATPase. The antibody inhibited tonoplast ATPase and H+-pumping activities. We conclude from these results that the 72-kDa polypeptide of the tonoplast H+-ATPase contains an ATP- (or nucleotide-) binding site that may constitute the catalytic domain. PMID- 2884219 TI - A cystine-dependent inactivator of tyrosine aminotransferase co-purifies with gamma-cystathionase (cystine desulfurase). AB - Tyrosine aminotransferase is stable in homogenates of rat liver, but not when L cystine or L-cysteine is added, which causes the enzyme to be reversibly inactivated due to oxidation of thiol groups. By monitoring inactivation of the aminotransferase in the presence of L-cystine, a factor responsible for this loss of activity was purified from rat liver. The factor required vitamin B6 and co purified with gamma-cystathionase during numerous steps. Highly purified inactivating factor contained a protein that was identical in size and isoelectric point to cystathionase but also contained a dissimilar peptide that appeared to be unrelated to cystathionase. Cystathionase and the cystine dependent inactivator shared several catalytic activities, including the hydrolysis of cystathionine, desulfuration of cystine, and desulfhydration of cysteine. During incubation of L-cysteine with the purified factor, hydrogen sulfide was generated but no inactivation of the aminotransferase occurred, suggesting that cysteine-dependent inactivation requires additional mechanisms. An insoluble inactivator of tyrosine aminotransferase that is produced during the reaction may be elemental sulfur, since colloidal suspensions of sulfur also inhibited the enzyme. Another inhibitor fractionated with high molecular weight substances; this may be protein-bound sulfane. PMID- 2884221 TI - The use of coral as a bone graft substitute. AB - Experiments have been performed to investigate the use of coral skeletons as bone graft substitutes. Skeletal fragments of different coral genera were implanted into cortical and spongy bone defects and used to bridge transcortical resections in the femur. The implant site was monitored for up to 18 months. Radiographically, both cortical and spongy bone defects were at least partially filled by new bone after 8 weeks while the implants underwent continuous resorption. Coral resorption and replacement by new tissue was also observed in the transcortical resections. The process of resorption was attributed to the enzymatic attack, especially carboanhydrase. This was confirmed by experiments in which dogs were implanted with coral in transcortical resections and treated daily with acetazolamide, a carboanhydrase inhibitor; the absorption appeared delayed and the resections failed to heal. PMID- 2884222 TI - Experience with I-131-metaiodobenzylguanidine (MIBG): a retrospective study. AB - We report a retrospective study of two years experience with I-131 metaiodobenzylguanidine (MIBG). I-131 MIBG was prepared locally and was found to have decreased background activity as compared with other available commercial preparations from Great Britain and the United States. Fifty-nine patients were studied with a total of 65 scans. The study included 11 members of a family with multiple endocrine adenomatosis (MEA) type II syndrome. Of 16 patients found to have abnormal scans, 12 had disease confirmed surgically. These cases consisted of nine pheochromocytomas, one paraganglioma, one neurilemmoma, and one neuroblastoma. MIBG scans for pheochromocytoma detection had an accuracy of 94.5%, a sensitivity of 100%, and a specificity of 93.5% in this study of patients with a high prior probability of the disease. PMID- 2884220 TI - Loss of unisite and multisite catalyses by Escherichia coli F1 through modification with adenosine tri- or tetraphosphopyridoxal. AB - Pyridoxal phosphate (PLP) and adenosine diphospho (AP2-PL)-, triphospho (AP3-PL) , and tetraphospho (AP4-PL)-pyridoxals (Tagaya, M., and Fukui, T. (1986) Biochemistry 25, 2958-2964) were tested as potential affinity probes for F1 ATPase of Escherichia coli. Both AP3-PL and AP4-PL bound and inhibited F1 ATPase, whereas PLP and AP2-PL were weak inhibitors. The concentrations of AP3-PL and AP4 PL for half-maximal inactivations of the multisite (steady state) ATPase activity were both 18 microM. The binding of these reagents to a reactive lysyl residue(s) was confirmed from the difference absorption spectra, and the stoichiometry of binding of [3H]AP3-PL to F1 at the saturating level was about 1 mol/mol F1. The analogue bound to both the alpha subunit (about two-thirds of the radioactivity) and the beta subunit (about one-third of the radioactivity). No inactivation of multisite ATPase activity or binding of AP3-PL was observed in the presence of ATP. F1 modified with about one mol of AP3-PL had essentially no uni- and multisite hydrolysis of ATP. The rate of binding of ATP decreased to 10(-2) of that of unmodified F1, and the rate of release of ATP was about two times faster. The equilibrium F1 X ATP in equilibrium F1 X ADP X Pi was shifted toward F1 X ATP, and no promotion of ATP hydrolysis at unisite was observed with excess ATP. These results suggest that the AP3-PL or AP4-PL bound to an active site, and catalysis by the two remaining sites was completely abolished. PMID- 2884224 TI - gamma-Glutamyl transpeptidase (gamma-GT) and maintenance of thiol pools in tumor cells resistant to alkylating agents. AB - Previous studies from this laboratory have established that acquired resistance of murine L1210 leukemia cells to L-phenylalanine mustard (L-PAM) and other alkylating agents is accompanied by a two-to threefold elevation in their glutathione (GSH) concentration (Biochem. Pharm. 31:121). In an attempt to gain insight into the mechanism by which resistant tumor cells maintain their increased GSH content, we have assessed the possible role of gamma-glutamyl transpeptidase (gamma-GT), a membrane bound enzyme involved in GSH metabolism. These results indicate that the enzyme is present in both sensitive and resistant murine L1210 leukemia cells but that the cellular content of gamma-GT is elevated two-to threefold in L-PAM resistant cells as compared to their sensitive counterparts. This elevation in enzymatic activity correlates well with the increased cellular GSH content in resistant cells. The results of a detailed kinetic analysis of gamma-GT activity indicate that there is no difference, between cell types, in the apparent Km of the enzyme for the gamma-glutamyl donor (L-gamma-glutamyl-p-nitroanilide) or the acceptor (glycylglycine). However, the apparent Vmax is increased two-to threefold in L-PAM resistant tumor cells. Investigation into the role of gamma-GT in the extracellular metabolism of GSH indicates that resistant tumor cells metabolize two-fold more GSH than do sensitive cells and that such metabolism results in a similar difference in the intracellular concentration of cysteine. Results of studies with cellular lysates also indicate a role for the enzyme in the supply of cysteine to the glutathione precursor pool of the tumor cell and in the maintenance of elevated GSH concentrations in cells resistant to alkylating agents. PMID- 2884223 TI - Lysosomal enzyme precursors in coated vesicles derived from the exocytic and endocytic pathways. AB - The molecular forms of two lysosomal enzymes, cathepsin C and cathepsin D, have been examined in lysosomes and coated vesicles (CVs) of rat liver. In addition, the relative proportion of these lysosomal enzymes residing in functionally distinct CV subpopulations was quantitated. CVs contained newly synthesized precursor forms of the enzymes in contrast to lysosomes where only the mature forms were detected. Exocytic and endocytic CV subpopulations were prepared by two completely different protocols. One procedure, a density shift method, uses cholinesterase to alter the density of CVs derived from exocytic or endocytic pathways. The other relies on electrophoretic heterogeneity to accomplish the CV subfractionation. Subpopulations of CVs prepared by either procedure showed similar results, when examined for their relative proportion of cathepsin C and cathepsin D precursors. Within the starting CV preparation, exocytic CVs contained approximately 80-90% of the total steady-state levels of these enzymes while the level in the endocytic population was approximately 10-13%. The implications of these findings are discussed with regard to lysosome trafficking. PMID- 2884225 TI - The influence of beta-adrenoceptor blockade on the lipolytic response to exercise. AB - The influence of beta-adrenoceptor blockade on the free fatty acid (FFA) response during and after submaximal exercise was studied in a group of normal volunteers. The study showed that the exercise-induced rise in serum FFA concentrations seen with placebo was reduced after pretreatment with propranolol. Furthermore, the palmitic, stearic, oleic and linoleic acid responses showed progressive attenuation with increasing doses of propranolol. Different beta blockers were studied using comparable doses: metoprolol and nadolol had little effect and produced FFA profiles that were similar to placebo whereas the changes on pindolol were comparable with those on propranolol. PMID- 2884226 TI - Simultaneous liquid chromatographic determination of seventeen of the major monoamine neurotransmitters, precursors and metabolites. I. Optimization of the mobile phase using factorial designs and a computer program to predict chromatograms. AB - Utilizing reversed-phase high-performance liquid chromatography (HPLC) with electrochemical detection and optimization of the mobile phase using factorial designs and a constructed computer program to predict chromatograms, it has been possible to obtain a satisfactory resolution of seventeen of the major monoamine neurotransmitters, precursors and metabolites. A rapid (less than 25 min) isocratic system for the simultaneous determination of 3,4 dihydroxyphenylalanine, dopamine, dihydroxyphenylacetic acid, 3-methoxytyramine, homovanillic acid, norepinephrine, normetanephrine, 3,4-dihydroxyphenylethylene glycol, 3-methoxy-4-hydroxyphenylethylene glycol, epinephrine, metanephrine, vanillylmandelic acid, 5-hydroxytryptophan, serotonin, 5-hydroxytryptophol and 5 hydroxyindoleacetic acid in addition to the internal standard isoproterenol is presented. The optimization strategy included selection of variables to optimize by a reduced factorial design a detailed study of these variables by a complete factorial design, theoretical predictions of chromatograms by a constructed computer program and test on the HPLC system. This optimization strategy can easily be applied to any problem of solute separation by liquid chromatography. PMID- 2884227 TI - Simultaneous liquid chromatographic determination of seventeen of the major monoamine neurotransmitters, precursors and metabolites. II. Assessment of human brain and cerebrospinal fluid concentrations. AB - The optimized chromatographic method procedure presented in Part I was employed for the assessment of human brain and cerebrospinal fluid neurotransmitters levels. The optimized sample preparation and chromatographic conditions permitted a rapid (less than 25 min), sensitive and semi-automated high-performance liquid chromatographic analysis which measures all major monoamine neurotransmitters, precursors and metabolites in human brain and cerebrospinal fluid. The brain specimen was deproteinized with perchloric acid (containing Na2EDTA and sodium sulphite), the internal standard and heparin were added and the samples were sonicated, centrifuged, filtered and injected directly into the chromatographic system. Cerebrospinal fluid was handled in a similar manner except that sonication was excluded. The regional distribution of monoamine neurotransmitter concentrations in human brain and cerebrospinal fluid is presented. PMID- 2884228 TI - Assay for tyrosine hydroxylase by high-performance liquid chromatography with fluorescence detection. AB - A sensitive assay method for tyrosine hydroxylase in rat brain and adrenal medulla by high-performance liquid chromatography with fluorescence detection is described. L-DOPA formed enzymatically from the substrate L-tyrosine and alpha methyldopa (internal standard), after clean-up with small cartridges of an activated alumina and a cation exchanger, Toyopak IC-SP M, are converted into the corresponding fluorescent compounds by reaction with 1,2-diphenylethylenediamine. The derivatives are separated by reversed-phase chromatography on TSK gel ODS 120T. The detection limit for L-DOPA formed enzymatically is 2 pmol per assay tube. PMID- 2884229 TI - Effects of age, duration and treatment of insulin-dependent diabetes mellitus on residual beta-cell function: observations during eligibility testing for the Diabetes Control and Complications Trial (DCCT). The DCCT Research Group. AB - To examine the effects of age and duration and treatment of insulin-dependent diabetes (IDDM) on residual beta-cell function, we measured the fasting and Sustacal-stimulated serum C-peptide levels in 610 conventionally treated IDDM patients (age, 13-39 yr; duration of diabetes, 1-15 yr) during eligibility screening for the Diabetes Control and Complications Trial (DCCT). Fasting and stimulated C-peptide values were closely correlated (r = 0.83; P less than 0.001), and both declined with increasing duration of disease. However, among patients who had been diabetic for more than 5 yr, 11% (33 of 296) of adults compared with 0 of 75 adolescents (P less than 0.001) retained substantial insulin secretory capacity. Patients with stimulated C-peptide levels greater than 0.2 pmol/mL had a significantly lower mean fasting plasma glucose level [177 +/- 6 (+/- SEM) vs. 222 +/- 6 mg/dL; P less than 0.001), a smaller rise in glucose after Sustacal administration (151 +/- 5 vs. 184 +/- 3 mg/dL; P less than 0.001), and lower hemoglobin A1C (8.4 +/- 0.2% vs. 9.3 +/- 0.1%; P less than 0.001) than the patients with a stimulated C-peptide level of 0.05 pmol/mL or less, even though the C-peptide secretors were receiving less insulin (0.52 +/- 0.02 vs. 0.78 +/- 0.02 U/kg X day; P less than 0.001). To determine the effects of treatment of beta-cell function, 33 patients with stimulated C-peptide values between 0.2 and 0.5 pmol/mL at entry in the DCCT were restudied 1 yr after randomization to standard treatment (n = 15) or an experimental (n = 18) treatment designed to achieve and maintain near-normal glucose levels. Although C peptide levels declined in both groups, experimental treatment was associated with slightly less of a decline in stimulated C-peptide values compared to Standard treatment. The results of C-peptide measurements in this large and well defined population of IDDM patients demonstrate that residual beta-cell function continues for a longer period of time in adults compared to adolescents with IDDM. This endogenous insulin secretion contributes significantly to metabolic control and may be prolonged by intensive insulin treatment regimens. PMID- 2884230 TI - Effect of estrogen on the growth hormone response to the alpha-adrenergic agonist clonidine in women with menopausal flushing. AB - The serum GH response to the alpha 2-adrenergic receptor agonist clonidine (0.15 mg, iv) was measured in 8 postmenopausal women with hot flushes before and during treatment with the conjugated estrogen premarin (1.25 mg, orally daily for 4 weeks), 9 normal premenopausal women, and 12 normal men. The men had a significantly greater GH response than did the age-matched premenopausal women (P less than 0.05). The mean individual peak GH response was significantly higher in the premenopausal compared with the postmenopausal women (P less than 0.05). Premarin decreased the number of hot flushes (P less than 0.01), but had no effect on the GH response to clonidine. These results suggest that estrogens do not enhance alpha 2-adrenergic mechanisms that regulate GH secretion and that improvement in menopausal flushing after estrogen therapy is not mediated by an effect on central alpha 2-adrenergic function. PMID- 2884231 TI - Current treatments with LHRH and its analogues. Recommendations of the ESHRE workshop. Anacapri, September 20, 1986. PMID- 2884232 TI - Crohn's disease-isolated mycobacteria are identical to Mycobacterium paratuberculosis, as determined by DNA probes that distinguish between mycobacterial species. AB - DNA extracted from an unclassified Crohn's disease-isolated Mycobacterium strain was cloned. The recombinant clones were radiolabeled and hybridized to restriction digests of mycobacterial DNA transferred to nylon membranes. Restriction fragment length polymorphisms (RFLPs) were identified that distinguished between mycobacterial DNA samples. Quantitative estimates of frequencies of DNA base substitution were also obtained. No RFLPs were detected between the DNA of three unclassified Crohn's disease-isolated mycobacteria and Mycobacterium paratuberculosis, although several RFLPs were detected that distinguished between M. paratuberculosis and both M. avium complex serovars 2 and 5. The frequency of DNA base substitution between M. paratuberculosis and M. avium complex serovar 2 was measured as 0.87 (+/- 1.2)%. PMID- 2884233 TI - Circulating somatostatin. Physiological regulator of pancreatic function? AB - The present study was designed to determine whether somatostatin is released into the circulation in sufficient amounts to regulate exocrine and endocrine pancreatic function and to evaluate the possible role of somatostatin as a hormonal regulator of the pancreas. Mean plasma somatostatin levels (SLI) increased from 11 +/- 2 pmol liter-1 to peak concentrations of 18 +/- 2 in six healthy male volunteers after a steak meal (P less than 0.05). Infusion of somatostatin inhibited hormone-induced exocrine pancreatic secretion and suppressed cerulein-stimulated pancreatic polypeptide (PP) secretion, but did not significantly change arginine-stimulated insulin and glucagon release at mean plasma somatostatin concentrations within the range seen after a meal. The amount of somatostatin released after a meal thus was of sufficient magnitude to inhibit exocrine pancreatic function and PP release. On the other hand, basal and arginine-stimulated glucagon and insulin secretions were not significantly affected by these plasma concentrations of intravenous somatostatin suggesting that the exocrine pancreas might be more sensitive to somatostatin than the islet cells. We conclude that somatostatin in concentrations within the range seen after a meal is a potent inhibitor of stimulated acinar cell function in man. The findings support the hypothesis that somatostatin acts as a true hormonal regulator. PMID- 2884234 TI - Regulation of lymphokine production and human T lymphocyte activation by 1,25 dihydroxyvitamin D3. Specific inhibition at the level of messenger RNA. AB - The steroid hormone, 1 alpha,25-dihydroxyvitamin D3 (calcitriol), has been shown to inhibit T cell proliferation, primarily through inhibition of interleukin 2 (IL-2) production. In these experiments, we show that calcitriol also markedly inhibited production of the lymphokine, gamma interferon (IFN-gamma), by activated human T lymphocytes. Regulation of both IL-2 and IFN-gamma production as well as transferrin receptor (TfR) expression by calcitriol was apparent at the messenger RNA (mRNA) level as determined by Northern blotting. The decrease in IL-2 and IFN-gamma mRNA that occurred with calcitriol treatment was coordinate and not apparent up to 12 h after phytohemagglutinin stimulation, whereas decreased accumulation of TfR mRNA was not present before 24-36 h. Furthermore, the effects of calcitriol on IL-2, IFN-gamma, and TfR mRNA accumulation were specific; actin mRNA accumulation was comparable between control and treated cells. These data indicate that calcitriol regulated proteins associated with T cell activation at the transcriptional level and that these effects were mediated in a specific, coordinate fashion. PMID- 2884236 TI - The effect of buspirone on panic disorder: a case report. PMID- 2884235 TI - Histochemistry of dipeptidyl aminopeptidase (DAP) II and IV in reactive lymphoid tissues and malignant lymphoma. AB - A modified histochemical method was used to show the presence of dipeptidyl aminopeptidase (DAP) II and IV in fixed, freeze dried, cryostat sections of tonsils, lymph nodes, and skin. In 14 reactive tonsils and lymph nodes both enzyme reactions were largely confined to T dependent areas where scattered positive lymphocytes were shown in the paracortical zones, while lymphocytes of germinal centres (B dependent areas) were negative. In either site some macrophages showed strong positivity for both enzymes. In 23 lymph node and two skin biopsy specimens of non-Hodgkin's lymphoma the neoplastic lymphocytes of 12 B cell lymphomas were completely unstained, whereas in the 13 cases of T cell lymphoma the neoplastic lymphocytes showed variable reactions with positivity for DAP II in eight and for DAP IV in seven, both reactions being positive in four and negative in two. Touch imprints of a lymph node from a case of Hodgkin's disease showed that the Reed-Sternberg cells were unreactive for both enzymes. The histochemistry of DAP II and IV may supplement other histochemical and immunological markers in the cytological classification of lymphomas. PMID- 2884237 TI - Early neuroleptic response: clinical profiles and plasma catecholamine metabolites. AB - Forty-seven psychotic inpatients who required neuroleptic treatment were studied with respect to some clinical and biochemical variables associated with early neuroleptic response. Compared to poor early responders, good responders were older at onset of illness and at index admission, less likely to have had a schizoid developmental history, and more likely to be married. There was a trend for good early responders to have received a diagnosis of affective psychosis or atypical psychotic disorder rather than schizophrenia or schizophreniform disorder. However, no behavioral symptom or sign differentiated good from poor early responders with the possible exception of pretreatment psychomotor retardation, which showed some association with poor response. Fasting plasma free homovanillic acid was significantly higher in the good response group and 3 methoxy-4-hydroxyphenethylene glycol showed a similar trend. PMID- 2884238 TI - Lithium-neuroleptic neurotoxicity is dose dependent. AB - Lithium-neuroleptic combination treatment was studied retrospectively. Six of 22 manic patients who were administered the combination developed neurotoxicity. The dosage of neuroleptic administered, and not the serum lithium level or lithium dose, predicted which patients became neurotoxic. PMID- 2884239 TI - Amantadine in the treatment of neuroendocrine side effects of neuroleptics. AB - An open-label reversal drug study was undertaken on 10 neuroleptic-treated schizophrenic inpatients to assess the impact of amantadine hydrochloride on presumed prolactin-mediated neuroendocrine side effects. Measures were conducted across 7 weeks, including a 2-week neuroleptic baseline, a 3-week neuroleptic plus-amantadine phase, and a 2-week return to the baseline regimen. Significant reduction with amantadine was observed on all six indices of neuroendocrine side effects: serum prolactin levels, body weight, gynecomastia/galactorrhea, breast tenderness, decreased libido, and amenorrhea. Improvement on these parameters was noted for as many as nine or all 10 patients, while in no cases was there worsening. In terms of motor and clinical effects, significant diminution of extrapyramidal and psycho-pathological symptoms was also achieved during this phase. The results suggested that amantadine may be beneficial for the treatment of neuro-endocrine side effects of antipsychotic medication owing to its ability to reverse neuroleptic-induced hyperprolactinemia. PMID- 2884240 TI - Sources of presumptive glutamergic/aspartergic afferents to the rat ventral striatopallidal region. AB - The distribution of presumptive glutamergic and/or aspartergic neurons retrogradely labeled following injections of 3H-D-aspartate (3H-D-Asp) into the ventral striatopallidal region was compared with the distribution of neurons labeled by comparable injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). The afferents labeled by 3H-D-Asp were a subset of those labeled by WGA-HRP. The major sources of afferents to the nucleus accumbens and olfactory tubercle that could be labeled by 3H-D-Asp were in the medial frontal and insular cortices; the olfactory cortex; the lateral, basolateral, and basomedial amygdaloid nuclei; and the midline nuclear complex of the thalamus. The corresponding afferents to the ventral pallidum arose in the central, medial, and basomedial amygdaloid nuclei and the midline thalamic nuclei. In addition, the nucleus of the lateral olfactory tract was moderately or heavily labeled by 3H-D Asp injections into all three areas, and cells were labeled in the subiculum following injection in the anteromedial part of the nucleus accumbens. Conversely the ventral striatopallidal structures themselves were, at best, sparsely labeled by any of the 3H-D-Asp injections. Neurons in the substantia nigra, ventral tegmental area, dorsal raphe, and locus coeruleus were labeled by WGA-HRP but not by 3H-D-Asp, except for an occasional cell in the raphe. The results indicate that 3H-D-Asp is a specific retrograde tracer and suggest that there are widespread, presumably excitatory, glutamergic and/or aspartergic inputs to the ventral striatum and pallidum. PMID- 2884242 TI - Purification and characterization of X-prolyl-dipeptidyl-aminopeptidase from Lactobacillus lactis and from Streptococcus thermophilus. AB - X-Prolyl-dipeptidyl-aminopeptidase recently was found in several lactic acid bacteria. This article describes the purification of the enzymes from Lactobacillus lactis and Streptococcus thermophilus and compares their characteristics. Enzymes from both strains are serine-peptidases. They both have a molecular weight of about 165,000 daltons, an isoelectric point near 4.5, and are constituted of two subunits. The pH optimum of the enzyme isolated from L. lactis is 7.0, whereas the enzyme from S. thermophilus possesses a broad pH optimum between 6.5 and 8.2 with glycyl-L-prolyl-aminomethylcoumarin as substrate. Below pH 5, both enzymes are unstable; however, that from S. thermophilus is more rapidly denatured. The enzyme from S. thermophilus is more sensitive to heat than the corresponding enzyme from L. lactis. Enzymes from the both strains have different specificities towards various substrates and are differently effected by metals, chelators, and other inhibitors. The importance of this enzyme for the metabolism of lactic acid bacteria is discussed. PMID- 2884241 TI - The brainstem projection to the lateral geniculate nucleus in the cat: identification of cholinergic and monoaminergic elements. AB - The pontomesencephalic projection to the dorsal lateral geniculate nucleus (dLGN) of the cat was analyzed by combining retrograde transport of rhodamine-labeled latex spheres and immunohistochemistry. After injections of latex beads into the dLGN, sections of the brainstem were treated immunohistochemically for choline acetyltransferase (ChAT), serotonin (Ser), tyrosine hydroxylase (TH), and dopamine-beta-hydroxylase (DBH). Essentially, six regions in the brainstem contained retrogradely labeled cells: the superior colliculus, the parabigeminal nucleus, the dorsal raphe nuclei, the parabrachial area of the central tegmental field, the marginal nucleus of the brachium conjunctivum, and the nucleus coeruleus. Furthermore, isolated retrogradely labeled cells were present in the central nucleus of the raphe, in the cuneiform nucleus, and in the periaqueductal gray. Most serotoninergic double-labeled cells were found in the medial and lateral divisions of the dorsal raphe nuclei, but a few were also present in the central nucleus of the raphe. In the sections immunostained for ChAT, double labeled cells were located in the central tegmental field, in the marginal nucleus of the brachium conjunctivum, and in the nucleus coeruleus. In the sections treated for TH and DBH, double-labeled cells showed a similar distribution, and like the ChAT(+) cells, they were located mainly in the central tegmental field, in the marginal nucleus of the brachium conjunctivum, and in the nucleus coeruleus. In these regions the cholinergic and noradrenergic cells that projected to the lateral geniculate nucleus were intermingled, the former predominating rostrally and the latter caudally. The majority of retrogradely labeled cells were located in the region of the central tegmental field in the vicinity of the brachium conjunctivum, and most of these cells were also ChAT immunoreactive. We, therefore, conclude that the cholinergic projection is the most important of the central core projections ascending to the dLGN. PMID- 2884243 TI - Effects of feeding monensin to lactating goats: acetyl coenzyme A carboxylase, hormone-sensitive lipase, plasma glucose, and circulating hormones. AB - These trials explored metabolic events associated with monensin-induced changes in milk composition. In trial 1, diets containing 0 or 33 ppm monensin sodium were fed ad libitum to separate groups of 7 mature lactating goats. In trial 2, diets containing 0 or 18 ppm monensin sodium were fed ad libitum to two groups with 5 mature (greater than 2 yr) and seven young (less than 2 yr) lactating does in each group. Blood was sampled at 1200 h and at 3 min after morning milking in both trials. Diets containing 33 ppm monensin increased serum growth hormone and plasma glucagon. Monensin (33 ppm) increased growth hormone from 13 to 60 ng/ml in samples taken 3 min after milking. Monensin (33 ppm) decreased insulin in these postmilking samples from 432 to 317 pg/ml but increased midday insulin in the samples taken between milkings from 279 to 349 pg/ml. Monensin did not affect plasma glucose or serum prolactin concentrations. Monensin fed at 18 ppm did not affect growth hormone, glucagon, adipose acetyl CoA carboxylase activity, hormone sensitive lipase, or glucose concentrations. Young animals had higher growth hormone, glucose, and glucagon than mature does. The results indicate that effects of milk production intensity can be more important than monensin treatment on milk composition and circulating hormone concentrations. PMID- 2884245 TI - The prevention of infectious diseases by immunization. PMID- 2884244 TI - Technical aids for dermabrasion. AB - Since the introduction in the 1940s of an effective method for facial dermabrasion using the wire brush, there have been many ancillary procedures developed. Preoperative aids include scar elevation and punch grafting of deep scars prior to dermabrasion. Retinoic acid can prime the skin for more rapid healing. Gas sterilization of electrical equipment eliminates cross-contamination between patients. Intraoperative improvements include regional block anesthesia of the face, staged narcotic administration and newer methods of facial prechilling, and criteria for the ambient air in the operatory. Gentian Violet staining of the face and use of microfoam tape to delineate the mandibular boundary of a dermabrasion are helpful. The use of a custom handle for the spray refrigerant, the safety of Turkish towels used for retraction, and the application of a sharp Buck's curette make the procedure simpler and more effective. Postoperative aids include the use of systemic steroids and the new biological dressings which simplify the postoperative recovery period. PMID- 2884246 TI - The effect of chronic administration of hydroxyzine on hydroxyzine pharmacokinetics in dogs. AB - Subsensitivity to H1-receptor antagonists has been attributed to autoinduction of enzyme systems and increased clearance rates during chronic drug administration. We studied the changes in serum half-life values and clearance rates in dogs who were administered hydroxyzine, 0.7 mg/kg, intramuscularly, daily, for 150 days. Pharmacokinetic studies were performed on the first day of drug administration, and on days 30, 60, 90, 120, and 150. The mean serum half-life value on day 30, 60, and 120 was significantly longer (p less than 0.05) than that of 2.4 +/- 0.3 hours obtained on day 1. The mean clearance values obtained on days 30, 60, 90, 120, and 150 were significantly slower (p less than 0.05) than the value of 25.12 +/- 4.13 ml/min/kg obtained on day 1 but were not significantly different from each other. Mean serum hydroxyzine concentrations were often significantly higher on the later study days than on day 1. The mean apparent volume of distribution values obtained on days 30, 60, 90, 120, and 150 did not differ significantly from the value of 5.0 +/- 1.5 L/kg obtained on day 1. This study adds to the mounting evidence that subsensitivity to the effects of an H1-receptor antagonist is not due to autoinduction of enzyme systems, more rapid clearance of the drug, and lower concentrations of the drug in serum and tissue. PMID- 2884247 TI - Phenothiazine-induced oculogyric crisis. AB - Extrapyramidal symptoms such as torticollis, oculogyric crisis and blepharospasm are typical manifestations of phenothiazine-induced drug reactions. Widespread use of such drugs, especially in children make these symptoms relatively commonplace. A case of phenothiazine-induced oculogyric crisis is presented. Included is a discussion of phenothiazine pharmacology. PMID- 2884249 TI - Dentistry in the emergency department. AB - Dental problems are commonly seen in the emergency department. Although most emergency physicians have had little formal training in dentistry, the majority of these problems can be diagnosed and treated without the need for emergent dental consultation. The necessary procedures may require initial instruction by a cooperative consultant but are easily learned and well within the scope of practice of the emergency physician. Time invested in familiarization with the diagnosis and treatment of the more common dental problems will be rewarded with patient satisfaction. PMID- 2884248 TI - Detection of thyroid-stimulating antibodies in thyroid diseases, employing rat thyroid fragment perifusion. AB - The technique of perifusing rat thyroid fragments was used to investigate the presence of thyroid-stimulating antibodies (TSAb) in the sera of 48 patients. Response to IgG was measured by determining the mean rate of release of T4 (R) during a 30-min perifusion and the secretion peak (Imax) by means of samples taken every 5 min. Values found to be above the mean + 2 SD of the control values of R or Imax were considered to be positive. TSAb were found in all the 17 patients with untreated Graves' disease (GD) and in the 2 treated with antithyroid drugs, but not in the 3 who had undergone surgery or 131I treatment or in the 2 on corticosteroid treatment. TSAb were also found in 2 out of 3 patients with untreated nodular toxic goiter (UNTG) and in 6 out of 8 with diffuse nontoxic goiter (DNG) but at lower levels. In the untreated GD group, R and Imax correlated significantly with the corresponding IgG concentrations (from 90 to 800 micrograms/ml), suggesting TSAb activity which can be compared from one patient to another. TSAb activity did not correlate with thyroid function tests in any group. In all the groups it induced an early secretion peak followed by a decreasing response throughout the stimulation period, as was previously found with 65 mIU/ml TSH. The specificity of this technique was verified by five different control methods: the perifusion technique was checked by using KRBG buffer alone; sera were studied from a group of healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884250 TI - Gastro-oesophageal reflux and alcoholic cirrhosis. A reappraisal. AB - The oesophageal pH was recorded for 3 h after a test-meal in 27 healthy control subjects (group I), 40 patients with alcoholic cirrhosis (group II), and 22 patients with a normal liver and symptoms of gastro-oesophageal reflux (control refluxers). Gastro-oesophageal reflux was observed in 10 of the cirrhotic patients. Marked reflux episodes lasted longer in cirrhotic refluxers than in control refluxers (P less than 0.05). The frequency of ascites, bleeding from ruptured oesophageal varices, peripheral neuropathy and hepatic encephalopathy were not significantly different according to presence or absence of reflux. Plasma concentrations of gastrin, somatostatin, motilin and vasoactive intestinal peptide (VIP) were measured in groups I and II. Fasting plasma motilin levels, and the release of motilin and of VIP after the meal were higher in group II than in group I. Basal levels and post-prandial profiles of the four peptides tested did not differ between cirrhotics with or without gastro-oesophageal reflux. We conclude that in patients with alcoholic cirrhosis: gastro-oesophageal reflux is frequent (25%) and characterized by prolonged reflux episodes; reflux is not correlated with the degree of liver failure and plays no significant role in the rupture of oesophageal varices; and raised plasma motilin and VIP levels cannot account for the high incidence of reflux in cirrhotics. PMID- 2884251 TI - Purification and identification of murine epidermal dendritic cells: flow cytometry and immunogold labeling. AB - We report on application of flow cytometric and immunogold labeling techniques to purify and identify two types of murine epidermal dendritic cells: Langerhans cells (LC) and Thy-1-positive dendritic epidermal cells (Thy 1+-dEC). After density centrifugation of epidermal cell (EC) suspensions through Ficoll gradients. IA-positive LC and Thy 1+-dEC are labeled with monoclonal antibodies (fluorescein-conjugated anti-IAd for LC and anti-Thy 1.2-biotin, followed by avidin-phycoerythrin, for Thy 1+-dEC). The fluorescence-activated cell sorter (FACS) is then used to obtain 95-98% pure populations of these dendritic cells with a yield of 2-4 X 10(6) cells and a viability of 80-90%. A post-fixation, pre embedding immunogold labeling technique using 15 nm and 40 nm colloidal gold particles is employed to identify LC and Thy 1+-dEC, respectively, to confirm the purity of the sorting and to estimate the number of IA antigenic sites per LC. With transmission electron microscopy, ultrastructural morphology of sorted LC is preserved; however, Birbeck granules are markedly diminished compared to the pre sorted population of LC. In contrast, characteristic dense-core granules are readily visualized in sorted Thy 1+-dEC. Purification of epidermal dendritic cells by flow cytometry may be a useful technique to employ in functional studies of epidermal dendritic cells. PMID- 2884252 TI - Dietary sodium restriction, blood pressure and sympathetic activity in spontaneously hypertensive rats. AB - Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were started at birth on sodium diets ranging from severely deficient (9 mumol) to a regular intake (101 mumol Na+/g food). Blood pressure and sympathetic activity were assessed at 6 and 16 weeks of age. At either age, SHR on 9 mumol Na+ failed to develop hypertension. Spontaneously hypertensive rats on 17 mumol Na+ exhibited significant blunting of the hypertension; SHR on 26 mumol showed a small amelioration. At 6 weeks, basal plasma noradrenaline was similar in SHR and WKY on 9 and 101 mumol Na+, whereas plasma adrenaline was increased in SHR at the lowest sodium level. At 16 weeks, both catecholamines were significantly increased in SHR on the 9 and 17 mumol sodium diet versus SHR on the control diet. Blood pressure responsiveness to noradrenaline was significantly decreased on 9 mumol Na+, but to a similar extent in both strains. In contrast, the blood pressure lowering effect of ganglionic blockade was markedly blunted in SHR on 9 mumol Na+ and to a lesser extent on 17 mumol Na+ (both for percentage and absolute decrease) and 26 mumol Na+ (only for absolute fall); however, this did not occur in WKY over the diet-range used. We conclude that a sodium-deficient diet from birth prevents/blunts the development of hypertension in SHR, at least partly by decreasing the pressor effect of the sympathetic nervous system. PMID- 2884253 TI - Time-course of changes in cardiac hypertrophy and pressor mechanisms in two kidney, one clip hypertensive rats during treatment with minoxidil, enalapril or after uninephrectomy. AB - In rats with severe two-kidney, one clip (2-K,1C) hypertension the time-course of changes in left and right ventricular (LV and RV) weight and LV dimensions was assessed following initiation of chronic treatment with minoxidil, enalapril or removal of the clipped kidney in relation to changes in blood pressure (BP) and sympathetic activity, as well as plasma and blood volumes. Minoxidil decreased BP markedly, but tolerance to the antihypertensive effect developed after 2-3 weeks. In contrast, enalapril or uninephrectomy caused a rapid and persistent normalization of BP. Significant increases in LV and RV weight occurred after 3-5 weeks of treatment with minoxidil. Left ventricular wall thickness decreased over the initial 1-2 weeks and then returned to untreated levels. Left ventricular internal dimensions showed an increase after 1-2 weeks of minoxidil, which persisted with more prolonged treatment. With enalapril, regression to normal occurred for both LV and RV weight within 1 week of treatment. Following uninephrectomy a more gradual regression took place and normal cardiac weight was not obtained until 3 weeks. Indices of sympathetic activity (plasma catecholamines, BP response to hexamethonium or heart rate) did not differ significantly in minoxidil treatment versus untreated hypertensive rats from 2 to 35 days of treatment. A significant increase in heart rate was found after 1 day of minoxidil and a decrease after enalapril. Plasma and blood volumes were elevated in minoxidil-treated rats from 7 to 35 days, as well as initially after uninephrectomy. Therefore, in 2-K, 1C hypertensive rats long-term treatment with minoxidil induces both RV hypertrophy and LV eccentric hypertrophy. Changes in cardiac volume load may play a major role in the differing effects of different antihypertensive therapies on cardiac hypertrophy. PMID- 2884254 TI - The interaction of the xid and me genes. AB - The murine "motheaten" (me) mutation has been bred onto the NFS background and combined with the X-linked immunodeficiency (xid) mutation to investigate the effect of the xid-induced B cell maturational block on the widespread immune dysfunction, high levels of autoantibodies, and early mortality found in the motheaten mice. The xid markedly reduced spontaneous IgM secretion by spleen cells, serum IgM, anti-ssDNA antibodies, anti-bromelain-treated-erythrocyte antibodies, and T cell binding (but not thymocytotoxic) antibodies; however, neither phenotype nor mortality was affected, suggesting that other factors are responsible for early death. Marked expansion of the Ly-1+ B cell pool was prevented by xid in the motheaten mouse leaving only a very small population of sIgM-positive B cells. This failure of non-Ly-1+ B cell development in me/me X xid mice suggests that me/me leads to inhibition of non-Ly-1+ B cells and preferential expansion of Ly-1+ B cells in motheaten mice, perhaps as a result of their high levels of maturation and activation factors. PMID- 2884255 TI - Role of interleukin 2 (IL 2) and hemopoietin-1 (H-1) in the generation of mouse natural killer (NK) cells from primitive bone marrow precursors. AB - The development of natural killer (NK) cells from bone marrow (BM) precursors was studied. Recombinant interleukin 2 (IL 2) was able to induce the in vitro development of NK cells when added to cultures of mouse BM cells. Treatment of donor mice with 5-fluorouracil (150 mg/kg i.v.), which eliminates more differentiated cells but spares less differentiated cells, appears to augment NK cell development. The "NK stem cell" was found to be asialo GM1-, Thy-1+, Lyt-2-, and Lyt-1-. The cells generated in vitro had a typical phenotype of NK cells, being asialo GM1+, Lyt-5+, Thy-1+, Lyt-2-, and Lyt-1-. These effector cells also had specificity characteristics of NK cells lysing the NK-susceptible YAC-1 and K562 targets, but not the NK-resistant EL/4 or allogeneic and syngeneic blasts. Hemopoietin-1 (H-1), a factor which acts on very primitive multipotent BM cells, was able to cooperate with IL 2, increasing the development of NK cells. In contrast, other factors such as interleukin 3 or colony-stimulating factor did not cause induction of NK activity when added to cultures of BM cells, indicating that this effect, i.e., induction of NK cell development, is peculiar to IL 2. These results indicate that IL 2 can act as a differentiation as well as growth factor for NK cells, and that H-1 can promote the development of functional activity in a lymphocyte subpopulation as well as affect the differentiation of myelomonocytic and other cell lineages. This experimental system appears quite useful for characterization of BM precursors for NK cells, and should help to better understand the relationship of the NK cell lineage to the T cell or other lineages. PMID- 2884256 TI - Characterization of cytotoxic cells in mice rendered neonatally tolerant of MHC alloantigens: evidence for repertoire modification. AB - A common prediction of clonal deletion/inactivation hypotheses is that cells with high avidity for tolerogen are preferentially eliminated, with low avidity cells being most likely to escape the tolerance induction mechanism. Thus it would be expected that the tolerogen-specific cells in tolerant mice would have a different repertoire than those in normal mice. To find evidence in favor of this prediction, neonatal B10.A mice were rendered tolerant to B10 by the injection of 15 X 10(6) (B10.A X B10)F1 spleen and bone marrow cells, and tolerance was assessed by the acceptance of B10 skin grafts for greater than 50 days. Mice rendered tolerant in this manner contain severely reduced (to less than 10% of normal) but detectable numbers of tolerogen-specific cytotoxic cell precursors that can be activated in the presence, but not absence, of exogenous interleukin 2. Spleen cells from the tolerant animals were compared with those of normal B10.A mice with respect to the expression of differentiation markers on the surface of B10-specific cytotoxic cells and their precursors, and the relative strength of the anti-B10 response toward Kb and Db as a measure of the repertoire of the cytotoxic cell populations. The T cell nature of the tolerogen-specific cytotoxic cells in both normal and tolerant mice was confirmed by their susceptibility to lysis by anti-Thy-1 or Lyt-2 antibody and complement. More importantly, cold target inhibition experiments showed that cytotoxic T cells from tolerant mice were inhibited to a greater degree by B10.A(2R) (KkDb) cold targets than B10.A(5R) (KbDd), suggesting that the response was preferentially directed at the D end of H-2, in direct contrast to normal B10.A spleen cells, which show a preferential response against Kb. Measurement of the frequency of anti-Kb and anti-Db cytotoxic T cell precursors in the spleens of normal and tolerant mice confirmed the differential specificities seen in the cold target experiments. The data suggest that neonatal tolerance induction results in repertoire modification of the anti-tolerogen response rather than a uniform decrease in anti-tolerogen reactivity. Possible mechanisms to explain the alteration in the repertoire of tolerant mice are discussed. PMID- 2884258 TI - Epidermal cells in activation of suppressor lymphocytes: further characterization. AB - Intravenous administration of hapten-coupled, high-density (density greater than 1.077) epidermal cells (HD-EC) to mice results in the appearance of transferable splenic T suppressor (Ts) cells as assayed in adoptive transfer experiments. Depletion of I-A bearing cells from the HD-EC population before hapten coupling prevents these cells from inducing Ts cell formation, whereas depletion of Thy-1 bearing cells from the HD-EC cell preparation has no effect. When HD-EC are adhered to glass for 2 hr, the ability to induce Ts cell formation resides in the adherent population. Exposure of HD-EC to a dose of ultraviolet radiation (UVR) that largely abrogates the ability of hapten-coupled EC to immunize mice for a DTH response does not affect the ability of these cells to activate Ts cells. Treatment of mice with i.p. administration of 20 mg/kg of cyclophosphamide 2 days before EC harvesting abrogates the ability of HD-EC from these mice to induce Ts cell formation. HD-EC from B10.A(3R) (I-Jb) but not B10.A(5R) (I-Jk) mice induce Ts cell formation in B10.A(3R) mice, demonstrating that the ability to do so is restricted by the I-J locus. Transmission electron microscopy of adherent HD-EC populations demonstrated that two cell types were present. One type had the characteristics of keratinocytes; the other was monocyte-like and resembled Langerhans cells or indeterminate cells in many aspects. Immunoelectron microscopy revealed this second cell type to bear I-A/I-E antigen. These cells were T-200 positive and Mac-1 negative by immunoperoxidase staining. Extensive examination by light and electron microscopy failed to reveal any dermal components in the EC populations; however, a very small degree of dermal contamination cannot be excluded. Thus, EC that activate afferent-acting Ts cells are high-density, I-A+, Thy-1-, I-J restricted, glass adherent, and functionally UVR resistant and cyclophosphamide sensitive. PMID- 2884259 TI - In vivo immunosuppression by pan-T cell antibodies relates to their isotype and to their C1q uptake. AB - There is considerable interest in the use of monoclonal anti-T cell antibodies for immunosuppression during organ transplantation. However, the in vitro cytotoxic titers of these monoclonal reagents do not correlate with their immunosuppressive potency when injected in vivo. A relationship nevertheless seems to exist between immunosuppression and the isotype of anti-mouse Thy-1 antibodies, because among several anti-Thy-1 antibodies of mouse and rat origin, the only two found to cause immunosuppression in vivo belonged to the rat IgG2b and mouse IgG2a isotype. We show here that a quantitative positive correlation exists between an antibody-induced humoral effector mechanism and immunosuppression. We measured the uptake of the C1q complement subunit by polyclonal rabbit and rat anti-thymocyte globulin and also seven monoclonal anti Thy-1 antibodies in an immunohistochemical assay or a radioimmunoassay. Immunosuppression was studied in a murine graft-vs-host and skin allograft model. Our results suggest strongly that a stable association between the C1 protein and a potential binding antibody is an essential prerequisite of antibody-dependent cell inhibition in vivo that suppresses the immunoresponse against strongly incompatible transplantation antigens. PMID- 2884257 TI - Suppression of macrophage cytostatic activation by serum retinoids: a possible role for transglutaminase. AB - Mouse resident peritoneal macrophages, activated in vitro with murine recombinant interferon-gamma and lipopolysaccharide in the presence of sera from different sources, showed marked differences in their abilities to inhibit murine adenocarcinoma cell growth, and in induced activity of the enzyme, tissue transglutaminase. The extraction of lipids from the serum abolished its ability to induce tissue TGase activity and to inhibit cytostatic activity, but these capabilities were fully restored by readdition of all trans-retinol or all trans retinoic acid at physiological concentrations. Addition of dansylcadaverine, a competitive inhibitor of TGase, resulted in complete recovery of macrophages from retinoid-induced suppression of cytostatic activity. These results suggest that endogenous retinoids play an important role in the regulation of macrophage mediated cytostatic activity in a process that is independent of prostaglandin secretion but seems to involve the protein cross-linking enzyme, tissue transglutaminase. PMID- 2884261 TI - Differential expression of the human Thy-1 gene in rodent-human somatic cell hybrids [corrected]. AB - Thy-1 is a cell surface differentiation marker which shows distinct patterns of tissue-specific expression in different species. In man, the Thy-1 antigen is encoded by chromosome 11. We have examined the regulatory signals determining human Thy-1 expression through serologic analysis of rodent-human somatic cell hybrids retaining human chromosome 11 in which the fusion partners belong to distinct differentiation lineages. Cell surface expression of human Thy-1 was determined by mixed hemadsorption assays with two monoclonal antibodies (mAb), K117 and L127, shown to detect authentic human Thy-1 through analysis of COS-7 monkey kidney cells transfected with a cloned human Thy-1 gene. Three different patterns of human Thy-1 expression were observed when hybrid cells, constructed with different human and rodent cell types, were tested with mAb K117 and L127. Hybrids formed between Thy-1+ human neuroblastoma cells and Thy-1- mouse neuroblastoma cells, or hybrids between Thy-1+ human fibroblasts and the Thy-1- mouse kidney carcinoma, RAG, retain human Thy-1 expression. In contrast, hybrids formed between either Thy-1+ human neuroblastoma cells or Thy-1+ human fibroblasts and Thy-1- mouse L cells lose expression of human Thy-1 even though chromosome 11 is retained. Finally, hybrids formed between Thy-1- human peripheral lymphocytes or a Thy-1- lymphoblastoid B cell line and Thy-1- Chinese hamster fibroblasts begin to express human Thy-1. These studies suggest that both positive and negative trans-acting signals may play a role in the tissue-specific regulation of the human Thy-1 gene. PMID- 2884262 TI - Cloning and expression of murine lymphotoxin cDNA. AB - The murine lymphotoxin (LT) gene has been cloned and used to identify cDNA clones in a library prepared from activated murine T cell mRNA. A recombinant murine genomic library was screened with a human lymphotoxin cDNA probe, resulting in the isolation of the entire LT gene. The murine LT gene structure is similar to the human gene, containing three intervening sequences. An activated murine T cell cDNA library was prepared with poly(A)+ RNA isolated 7 hr after concanavalin A stimulation of an L3T4+ interleukin 2-dependent murine T cell clone. Two colonies of the cDNA library that contained inserts that hybridized with the murine LT gene probe were sequenced and were used to construct expression plasmids. The amino acid sequence deduced from the cDNA indicates that murine LT is highly homologous to human LT (74%) and is related to murine tumor necrosis factor (35% homology). The cDNA was transcribed and was translated in vitro, and was expressed in COS-1 cells. This has resulted in the production of LT biological activity. PMID- 2884260 TI - Proliferating cell nuclear antigen (PCNA)/cyclin in activated human T lymphocytes. AB - Proliferating cell nuclear antigen (PCNA), also called cyclin, is an intranuclear polypeptide whose synthesis reaches its maximum during the S-phase of the cell cycle. PCNA is expressed in several kinds of proliferating cells, one of which is the mitogen-stimulated human peripheral blood lymphocyte. PCNA expression increases from the late G1 phase through the S-phase of the cell cycle. This study is focused on the regulation of PCNA expression during the G1 phase of human T lymphocytes and on the relationship between PCNA expression and the rate of T cell proliferation. Special use is made of human autoantibodies to PCNA and the development of flow cytometry to label this intranuclear polypeptide. Unstimulated purified human peripheral blood T cells were PCNA negative. T cells treated with monoclonal antibody (64.1) to the CD3 complex expressed receptors for IL 2 but did not express PCNA until exogenous IL 2 was added to the culture. PCNA expression as well as the entry of the cells into S-phase could be inhibited by IL 2 receptor antibodies. Transferrin receptors were expressed only in T cells that were stimulated with both 64.1 and exogenous IL 2. Transferrin receptors were detectable before the cells expressed PCNA. Thus, the onset of PCNA expression is a phase in cell proliferation that follows transferrin receptor expression but preceded DNA synthesis. Drugs like dexamethasone and cyclosporin, which affect the early part of G1, inhibited PCNA expression; whereas cytarabine (ara-C) and hydroxyurea, which affect the S-phase and prevent DNA synthesis, did not block PCNA expression. There was a close correlation between the number of PCNA-positive cells and the number of S-phase cells in unperturbed T cell cultures. The highest level of PCNA expression was seen in cells that were in the first cycle after stimulation. The results show that PCNA expression is regulated by a signal after IL 2 binding and that PCNA labeling is a precise indicator for human T cells that are committed to DNA synthesis. Comparing these results with previous observations on the expression of some other activation-associated antigens, we suggest that the onset of PCNA expression represents a discrete step in T cell activation. PMID- 2884263 TI - The use of an HTLV-I-infected human T-cell line (ATH8) in an interleukin-2 bioassay. AB - Biological interleukin-2 (IL-2) assays require cells that proliferate only in the presence of IL-2. The most often used human cells for this purpose have been phytohaemagglutinin (PHA)-stimulated buffy coat lymphocytes made dependent on IL 2. The results obtained by this T-blast method have not been easily reproducible and/or comparable due to differences in individual buffy coat batches. Murine cytotoxic T-cell lines (CTLL and CTLL-2) have been widely used in human IL-2 assays, but there remains a need for a human cell line. We have developed an IL-2 bioassay, based on the use of a human HTLV-I-infected Th-cell line, ATH8. These cells express IL-2 receptor and are totally dependent on extrinsic IL-2 for proliferation. The results of the ATH8 IL-2 assay were reproducible and comparable to those obtained with successful T-blast assays. ATH8 cells do not require a prolonged culture period before they are suitable for the IL-2 assay as do T-blasts. PMID- 2884265 TI - Pharmacological management of pain and symptom control in cancer. PMID- 2884264 TI - Some characteristics of a new isolate of Helicosporidium and its effect upon mosquitoes. PMID- 2884266 TI - [Homeotic genes and the homeobox]. PMID- 2884267 TI - [Molecular biology of bacterial behavior]. PMID- 2884268 TI - Arteriovenous shunting in experimental liver cirrhosis in rats. AB - The extent of systemic arteriovenous shunting (arteriovenous anastomotic blood flow) was assessed in rats with experimental liver cirrhosis and control rats by injecting 15 micron microspheres into the left ventricle and measuring the percentage of injected spheres trapped in the pulmonary circulation. Cirrhotic rats with body temperature maintained at 38 degrees C were found to have increased trapping of microspheres in the pulmonary bed when compared with control rats studied under similar conditions (8.2% +/- 2.2% vs. 3.6% +/- 0.8%, P less than 0.05). The extent of arteriovenous shunting was also measured in control rats maintained at various body temperatures (34 degrees to 40 degrees C) with and without prior alpha-adrenergic blockade with phenoxybenzamine (0.1 mg/kg). Both body warming and alpha-adrenergic blockade independently increased the extent of arteriovenous shunting. In cirrhotic rats, body warming also increased shunting. However, in contrast to findings in control rats, alpha adrenergic blockade did not further increase shunting in cirrhotic rats warmed to 40 degrees C. Moreover, the degree of shunting after combined body warming and alpha-adrenergic blockade was similar in cirrhotic and control rats. Our results indicate that increased peripheral arteriovenous shunting occurs in this model of experimental cirrhosis, and that the increased shunting may be related to altered physiologic regulation of arteriovenous anastomotic blood flow. PMID- 2884269 TI - [Effect of somatostatin on peripheral circulation. Preliminary study]. AB - Somatostatin is a cyclic tetradecapeptide widely distributed in the human cells; it has many physiological effects. Synthetic somatostatin, actually employed in some clinical conditions, was administered intravenously to normal and arteriopathic subjects. Rheography and plethysmography of lower limbs were performed before, during and after administration. A marked improvement of blood flow and a reduction of heart rate was observed after somatostatin infusion. Some hypotheses about the mechanism of action of somatostatin are discussed, especially the action on the sympathetic nervous system or the calcium-antagonist effect on the blood vessels. PMID- 2884270 TI - Somatostatin-like immunoreactivity in duck plasma, hypothalamus and neural lobe during post-hatch growth: comparison with plasma and pituitary growth hormone concentrations. AB - Variations in the concentrations of plasma and pituitary GH were determined in ducks for 66 and 87 days after hatch, and compared with somatostatin-like immunoreactivity (SLI) in the plasma, hypothalamus and neural lobe. Plasma GH levels gradually decreased during growth, while pituitary GH content increased. The concentration of pituitary GH increased during the first 3 weeks of age and remained relatively constant thereafter. The decline in plasma GH concentration was paralleled by a similar fall in the level of plasma SLI. While the content of hypothalamic SLI increased during development, the SLI concentration was maximal at 14 days of age and lowest in adults. The content and concentration of SLI in the neural lobe, in contrast, increased progressively during development. Gel filtration of hypothalamic and neural lobe extracts demonstrated that both young and older birds had two main peaks of SLI, corresponding to somatostatin-14 and somatostatin-28, and a third, larger form. The elution pattern of plasma SLI was similar in young and older birds and was principally composed of a large molecular species ('big' somatostatin), although an additional small peak eluting between somatostatin-28 and somatostatin-14 was eluted from a large pool of plasma from 90-day-old ducks. These results suggest that increased plasma GH levels in young birds do not result from a hypothalamic somatostatin deficiency nor from variations in molecular forms of SLI, and that the age-related decline in plasma GH concentration is not due to a deficiency in pituitary GH content. The decline in the circulating GH level during growth is probably due to an increase in hypothalamic somatostatin release. PMID- 2884271 TI - Pancreatic somatostatin, glucagon and insulin during post-hatch growth in the duck (Anas platyrhynchos). AB - Pancreatic somatostatin-like immunoreactivity (SLI), immunoreactive insulin (IRI) and glucagon-like immunoreactivity (GLI) were measured during growth in ducks. The content of each hormone increased progressively but at different rates in the dorsal, ventral and splenic lobes of the pancreas. In the almost fully grown duck, the splenic lobe contained 80 and 63% of the total content of GLI and SLI respectively but low levels of IRI (23%), which were highest in the dorsal lobe (53%). In contrast to the hormonal content, only total GLI concentrations increased during development, the SLI concentrations remaining stable and IRI concentrations declining during growth. Gel filtration of pancreatic extracts indicated that most of the SLI in the pancreas of young and adult birds was somatostatin-14, although somatostatin-28 was present in the ventral lobe of young birds and larger molecular forms were present in the ventral and dorsal lobes. These changes in pancreatic hormonal content and concentration are dissimilar to age-related changes in SLI, GLI and IRI previously observed in the plasma of ducks. Plasma levels of pancreatic hormones may thus be controlled by hormonal and/or neutral factors during post-hatch growth. PMID- 2884272 TI - Early genetic events in T cell development analyzed by in situ hybridization. AB - In situ hybridization was used to investigate the expression of T cell receptor (TCR) alpha, beta, and gamma mRNAs in developing fetal and adult precursor thymocytes. gamma transcription was observed at the earliest time tested (day 12), followed by beta 12 h later, and TCR alpha on day 16. The early beta transcripts appeared to be from unrearranged or incompletely rearranged (D-J-C) beta loci. V beta region transcription was first detectable on day 14 and transcription of different V beta genes was induced at different times. These results delineate a schedule sequence of TCR gene activation, which begins within 1 d after entry of stem cells into the fetal thymus. PMID- 2884273 TI - Physician assistants: current status of the profession. AB - In the two decades since the inception of the physician assistant concept in the United States, 52 physician assistant training programs have been established. Currently, approximately 16,000 physician assistants are employed by physicians and institutions throughout the country. Established to fill a perceived gap in primary health care delivery in the 1960s, the profession continues to serve mainly in primary care settings, with 43 percent of all physician assistants in family practice clinics. There is a trend, however, for physician assistants to fill health care gaps in other settings, such as long-term care institutions and correctional facilities. The clinical effectiveness of physician assistants has been demonstrated in terms of both quality of care and patient acceptance, and they are adept at adjusting to shifts in the health care marketplace. However, the real determinant of the future of the profession will be economic advantage. Recent changes in Medicare legislation now permit reimbursement for physician assistant services in nursing homes and hospitals, and payment under Medicaid has been approved in one half of the states. Given the cost effectiveness of physician assistants, their demonstrated competence and acceptability, and their adaptability to a variety of settings, the demand for their services is likely to continue. PMID- 2884274 TI - Neuroleptic-induced panic attacks in a patient with delusional depression. AB - Panic attacks occurred for the first time in a patient suffering from delusional depression during treatment with a combination of an antidepressant and a neuroleptic. His anxiety proneness along with a dysphoric response to the neuroleptic were deemed responsible for these attacks. It is proposed that neuroleptic-induced dysphoric responses may be responsible for therapeutic failure in some cases of psychotic depression. PMID- 2884275 TI - Differential effects of nerve growth factor and ciliary neuronotrophic factor on catecholamine storage and catecholamine synthesizing enzymes of cultured rat chromaffin cells. AB - The effects of nerve growth factor (NGF) and ciliary neuronotrophic factor (CNTF) on catecholamine content and in vitro activities of tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) were studied in adrenal chromaffin cells cultured from 8-day-old rats. Both NGF and CNTF enhanced chromaffin cell survival and partially prevented losses of adrenaline during the 4-day culture period in a dose-dependent manner. CNTF was more potent, although cellular levels of adrenaline and noradrenaline were not maintained. NGF did not add to the effect of CNTF. The effect of CNTF on catecholamine storage was not accompanied by changes in the activities of TH and PNMT. In contrast, NGF induced TH but not PNMT activity. These data indicate differences between the mechanisms by which NGF and CNTF affect adrenal chromaffin cells. PMID- 2884276 TI - Pentobarbital antagonizes the A1 adenosine receptor-mediated inhibition of hippocampal neurotransmitter release. AB - Barbiturates have been shown to be competitive antagonists at A1 adenosine receptors in radioligand binding studies. The present study investigates the effects of pentobarbital on the A1 receptor-mediated inhibition of neurotransmitter release from rabbit hippocampal slices. The inhibition of the electrically evoked release of [3H]noradrenaline by the A1 receptor agonist (R) N6-phenylisopropyladenosine (R-PIA) was antagonized by pentobarbital with an apparent pA2 value of 3.5. Low concentrations of pentobarbital alone altered neither basal nor evoked release of [3H]noradrenaline, whereas 1,000 microM pentobarbital enhanced the basal and reduced the evoked release. In the presence of 8-phenyltheophylline, pentobarbital (200 microM and 1,000 microM) reduced the evoked noradrenaline release. Pentobarbital also antagonized the inhibition of [3H]acetylcholine release by R-PIA. In contrast to the noradrenaline release model, the evoked release of acetylcholine was enhanced by the presence of pentobarbital (50-500 microM), an effect that was lost in the presence of 8 phenyltheophylline. These results indicate that pentobarbital, in addition to a direct inhibitory action at higher concentrations, has a facilitatory effect on neurotransmitter release by blocking presynaptic A1 adenosine receptors. The possible relevance of these findings for the excitatory effects of barbiturates is discussed. PMID- 2884277 TI - Solubilisation of a glutamate binding protein from rat brain. AB - Rat brain synaptic plasma membranes were solubilised in either 1% Triton X-100 or potassium cholate and subjected to batch affinity adsorption on L glutamate/bovine serum albumin reticulated glass fibre. The fibre was extensively washed, and bound proteins eluted with 0.1 mM L-glutamate in 0.1% detergent, followed by repeated dialysis to remove the glutamate from the eluted proteins. Aliquots of the dialysed extracts were assayed for L-[3H]glutamate binding activity in the presence or absence of 0.1 mM unlabelled L-glutamate (to define displaceable binding). Incubations were conducted at room temperature and terminated by rapid filtration through nitrocellulose membranes. Binding to solubilised fractions could be detected only following affinity chromatography. Binding was saturable and of relatively low affinity: KD = 1.0 and 1.8 microM for Triton X-100 and cholate extracts, respectively. The density of binding sites was remarkably high: approximately 18 nmol/mg protein for Triton X-100-solubilised preparations, and usually double this when cholate was employed. Analysis of structural requirements for inhibition of binding revealed that only a very restricted number of compounds were effective, i.e., L-glutamate, L-aspartate, and sulphur-containing amino acids. Binding was not inhibited significantly by any of the selective excitatory amino acid receptor agonists--quisqualate, N methyl-D-aspartate, or kainate. The implication from this study is that the glutamate binding protein is similar if not identical to one previously isolated and probably is not related to the pharmacologically defined postsynaptic receptor subtypes, unless solubilisation of synaptic membranes resulted in major alterations to binding site characteristics. Since solubilisation with Triton X 100 is known to preserve synaptic junctional complexes, it seems likely that the origin of the glutamate binding protein may be extrajunctional, although its functional role is unknown. PMID- 2884278 TI - Acute and long-term effects of chlorpromazine on glutamine synthetase and glutaminase in rat brain. AB - The effect of administration of chlorpromazine on the activity of glutamine synthetase and glutaminase and the content of glutamate and gamma-aminobutyric acid (GABA) in different regions of rat brain was studied in an investigation of the possible role of these amino acids in the lowering of the seizure threshold following prolonged administration of chlorpromazine. Chlorpromazine was administered at a dose of 20 mg/kg of body weight s.c. For the acute study, the animals were killed 20 min after a single injection. For the long-term study, the animals were treated every day with the same dose for 21 days and were killed 20 min after the last injection. The results showed an increase in glutamate level in each brain region investigated following long-term administration, but only in the cerebral cortex after a single dose. GABA levels showed an increase in the brainstem only in acute experiments. Glutamine synthetase activity was increased in all three regions after a single dose and only in cerebral cortex after long term administration. Glutaminase activity showed a decrease in cerebral cortex only after long-term administration of the drug. These results suggest the possible occurrence of a state of increased excitability in the brain as a result of long-term administration of chlorpromazine, thus contributing to the known complication of seizures. PMID- 2884279 TI - Calcium-dependent and -independent release of glutamate from synaptosomes monitored by continuous fluorometry. AB - An enzyme-linked fluorometric assay is described for the continuous monitoring of the unidirectional efflux of glutamate from guinea-pig synaptosomes. Glutamate efflux from freshly suspended, polarized synaptosomes occurs at 0.35-0.39 nmol min-1 mg of protein-1 and is not significantly affected by external Ca2+. KCl depolarization (30 mMKCl) in the absence of Ca2+ doubles this rate, whereas in the presence of Ca2+, the initial kinetics of the assay are consistent with the release in the first 5 s of 0.6 nmol mg of protein-1. The final extent of Ca2+ dependent release amounts to 1.9 nmol mg of protein-1, or 8.5% of the total intrasynaptosomal glutamate content. Preincubation of synaptosomes at 30 degrees C for 2 h before depolarization leads to a decrease in Ca2+-independent release and an increase in Ca2+-dependent release, consistent with an intrasynaptosomal relocation of the amino acid. PMID- 2884280 TI - Characterization of the exocytotic release of glutamate from guinea-pig cerebral cortical synaptosomes. AB - A continuous enzyme-linked fluorometric assay was used for determining the characteristics for glutamate exocytosis from guinea-pig cerebrocortical synaptosomes. Ca2+-dependent release can be induced not only by K+, but also by the Na+ channel activator veratridine and the Ca2+ ionophore ionomycin. K+ induced release can be inhibited by the Ca2+ channel inhibitor verapamil. Sr2+ and Ba2+ substitute for Ca2+ in promoting K+-induced release. Agents that would be predicted to transform the transvesicular pH gradient into a membrane potential are without effect on glutamate release. However, the protonophore carbonylcyanide p-trifluoromethoxyphenylhydrazone causes a time-dependent loss of exocytosis that is oligomycin insensitive and may be due to depletion of vesicular glutamate. The Ca2+-independent release of glutamate from the cytosol on depolarization is unchanged or promoted by metabolic inhibitors that lower the ATP/ADP ratio. In contrast. Ca2+-dependent release is ATP dependent and is blocked by the combined inhibition of oxidative phosphorylation and glycolysis. PMID- 2884281 TI - The effects of prolonged superfusions with acidic amino acids and their agonists on field potentials and horizontal cell photoresponses in the turtle retina. AB - The effects of prolonged superfusions with acidic amino acids and their agonists, kainic acid (KA) and N-methyl-D-aspartate (NMDA), on horizontal cells, and extracellular field potentials were studied in the turtle everted eyecup preparation using simultaneous intracellular and extracellular recordings. In a fresh preparation initial superfusions with each of the above agents usually induced a large (up to 60 mV) transient negative extracellular field potential recorded adjacent to horizontal cells, followed by a sustained negative potential of lesser amplitude (up to 10 mV). The amplitude of the sustained potential did not vary with subsequent superfusions, whereas that of the transient phase was reduced. KA and NMDA were much more potent (at least 300 times) in evoking these field potentials than either acidic amino acid. The horizontal cell transmembrane potential was monitored as the difference between the intra- and extracellular potentials. Superfusion with KA and NMDA produced a triphasic time course of the drug effect consisting of an initial depolarization with reduced photoresponses, a rehyperpolarization of the membrane accompanied by a growth of the light responses followed by a gradual depolarization and loss of photoresponses. Superfusion with the acidic amino acids usually produced a biphasic response that resembled qualitatively the first two phases of the response to KA and NMDA. This biphasic response was occasionally followed by a gradual depolarization and loss of the light response. The kinetics of the transient component of the field potential and the rapid reduction and regrowth of the photoresponses recorded during superfusion with these agents suggests an initial action of these drugs, which is of a nonsynaptic origin and which may be an expression of a drug-induced spreading depression. The kinetics of the photoresponses recorded during superfusion with KA, L-aspartate, and L-glutamate were similar but differed from those recorded during superfusion with NMDA. The difference in the effects of NMDA and KA on photoresponse kinetics suggests that two types of acidic amino acid receptors may be present in the outer plexiform layer of the turtle retina. PMID- 2884282 TI - Missed torsion of an undescended testis detected with testicular imaging. PMID- 2884283 TI - Effect of fluid volume on ipecac-induced emesis. PMID- 2884284 TI - Effect of milk on ipecac-induced emesis. PMID- 2884285 TI - Particulate contaminants of intravenous medications and infusions. AB - Particulate contamination in small volume parenteral medications has been studied and compared with that found in a selection of large volume infusions. Particle counts in 39 commonly used small volume medications and 7 large volume infusions were performed by an automated light blockage method (HIAC) or by optical microscopy. Based on these results and a random survey of drug therapy of intensive care patients, it is concluded that the contribution of intravenous medications to the total particle load received by such patients is likely to be many times greater than from infusion fluids. Until firm evidence regarding the harmful systemic effects of drug particles is available and the manufacturing regulations adjusted appropriately, final in-line filtration of infusions immediately proximal to the intravenous cannula should be considered when drugs are being given intravenously. PMID- 2884286 TI - Solubilities and intrinsic dissolution rates of sulphamethoxazole and trimethoprim. AB - The influence of pH on the dissolution rates and solubilities of sulphamethoxazole and trimethoprim have been examined. Sulphamethoxazole was evaluated in buffers of ionic strength 0.5 mol dm-3 over the pH range 0.45-7.8 and at 25, 32 and 37 degrees C. The minimum solubility of sulphamethoxazole was 28.1 mg/100 mL at pH 3.22 and 25 degrees C. Solubilities increased significantly with both increased and decreased pH. Intrinsic dissolution rates demonstrated a linear relationship with the solubility data. Trimethoprim solubility was both buffer- and pH-dependent. In both water and hydrochloric acid solution at 32 degrees C the solubility of trimethoprim increased from 50 mg/100 mL in water at pH 8.54 to a maximum of 1550 mg/100 mL at pH 5.5. This maximum solubility was in excess of that predicted theoretically and may be due to supersaturation. Below pH 2 the solubility of protonated trimethoprim diminished from 1125 mg/100 mL with decreasing pH. This was due to the common ion effect. Intrinsic dissolution rates increased as pH was decreased with hydrochloric acid from 6.00 to 1.78, but decreased at pH 1.48 due to the common ion effect. Dissolution profiles of trimethoprim showed complex patterns dependent upon pH. The profile was zero order at pH 6.00 and became distinctly stepwise at pH 5.5, this effect becoming less pronounced at lower pH values. This was reconciled in terms of the rate of formation of trimethoprim hydrochloride on the surface of the disc and the differing dissolution rates of this species and trimethoprim. A simple relationship between solubility and dissolution rate was not observed. PMID- 2884287 TI - Correlation between n-octanol/water partition coefficient and liquid chromatographic retention for caffeine and its metabolites, and some structure pharmacokinetic considerations. AB - A method to establish the correlation between the reverse phase high performance liquid chromatographic retention of caffeine and its metabolites and their n octanol/water partition coefficients is described. The log (P) values were always below zero, ranging from -0.02 to -2.03. The capacity factor quadratically back extrapolated to 100% water eluent (k'w) was used as the index of lipophilicity. The compounds examined gave a good correlation (r greater than 0.99) with log (k'w) if considered in separate series, depending on the substituent position. For a structure-pharmacokinetic relationship study, correlations were found between the partition coefficient and some pharmacokinetic parameters, suggesting that for drugs that are widely metabolized, any predictions of their disposition from physicochemical characteristics are hazardous. PMID- 2884288 TI - A preliminary pharmacokinetic study of the antimalarial drugs, proguanil and chlorproguanil. AB - Pharmacokinetic parameters for cycloguanil and chlorcycloguanil, the active metabolites of proguanil (Paludrine] and chlorproguanil (Lapudrine) have been measured in a bioassay which assesses the in-vitro growth inhibition of a cycloguanil- and chlorcycloguanil-sensitive strain of Plasmodium falciparum produced by dilutions of plasma collected after oral administration of the pro drugs. A single compartment model is applicable for cycloguanil with mean rate constants of elimination of 0.0624 h-1 and availability of 0.2398 h-1. The elimination profile for chlorcycloguanil indicates partition of drug into more than one compartment. In 2 of 10 subjects dosed with proguanil and 1 of 11 subjects dosed with chlorproguanil, the active metabolite levels were significantly lower than the mean for the other subjects. Abnormally low cycloguanil or chlorcycloguanil plasma levels may be of importance in relation to effective prophylaxis against malaria. PMID- 2884289 TI - On the mechanism of transport of salicylate and p-hydroxybenzoic acid across human red cell membranes. AB - The pH-dependence of efflux of salicylate and p-hydroxybenzoic acid (PHB) from human red cells indicates that the un-ionized species penetrates the membrane. No effect of the anion channel blocker 4,4'-diisothiocyano-2,2'-disulphonic stilbene was observed. The temperature-dependence of efflux suggests that the energy barrier to transport of salicylate and PHB is the transfer of the acids from water into the membrane, rather than transport through the membrane interior. Intracellular binding of both acids was found to be pH-dependent. PMID- 2884290 TI - Saturable uptake of cefixime, a new oral cephalosporin without an alpha-amino group, by the rat intestine. AB - The mechanism of intestinal uptake of cefixime, a new oral cephalosporin antibiotic, has been examined using the everted jejunum of rats. The initial uptake rates were apparently pH-dependent with the maximum rate at pH 5.0 and a 3 fold reduction at pH 7.0. The uptake at pH 5.0 followed mixed-type kinetics involving saturable and non-saturable processes in a manner similar to that for several amino-beta-lactam antibiotics. Cefixime uptake was inhibited significantly by 20 mM permeants such as cyclacillin, cephradine, benzylpenicillin, propicillin, glycyl-L-proline and glycyl-glycine. Replacement of Na+ in the medium with choline produced a slight but significant inhibition of cefixime uptake. In spite of the absence of significant inhibition by the amino acids glycine and proline, the dipeptide, glycyl-L-proline in Na+-free medium showed a marked inhibitory effect. The inhibition kinetics of cefixime uptake by glycyl-L-proline and cyclacillin were consistent with competitive-type inhibition. This study provides the first evidence of saturable intestinal uptake of a cephem antibiotic without an alpha-amino group in the side chain, suggesting transport through the dipeptide carrier system(s). PMID- 2884291 TI - Influence of beta-adrenoceptor-mediated relaxation on alpha-adrenoceptor-mediated contraction of rat pulmonary artery to adrenaline or noradrenaline. AB - Concentration-response (contraction) curves to either adrenaline or noradrenaline were obtained on isolated ring preparations of pulmonary artery from rats. In preparations from young rats the curve for adrenaline was bell-shaped, unless beta-adrenoceptors were blocked with propranolol (1 X 10(-6) M). The maximum contraction to adrenaline was less in the absence than in the presence of propranolol. In preparations from aged rats the adrenaline curve was no longer bell-shaped, even in the absence of propranolol. This reflected a decrease in the beta-adrenoceptor-mediated relaxant responses of preparations from aged rats, seen as a separation between the concentration-response (relaxation) curves to adrenaline on preparations (phenoxybenzamine-treated, KCl-contracted) from young and aged rats. In preparations from young rats the noradrenaline curve was not bell-shaped, but if the preparations were from young rats treated with thyroxine (T4), then a bell-shaped curve for noradrenaline was obtained, unless beta adrenoceptors were blocked by propranolol. These data could be explained by an increase in beta-adrenoceptor-mediated relaxant responses of preparations from T4 treated rats, seen as a separation in the concentration-response (relaxation) curves to noradrenaline on preparations from control and T4-treated rats, respectively. Thus alpha-adrenoceptor-mediated contractile responses of rat pulmonary artery preparations, to adrenaline or noradrenaline, can be attenuated by activation of beta-adrenoceptors, mediating relaxation, and the extent of this attenuation changes under the influence of factors, such as ageing or T4 treatment, which modify beta-adrenoceptor-mediated relaxation in this blood vessel type. PMID- 2884292 TI - Differentiation of calcium antagonists with respect to their effects in normal and skinned taenia caeci preparations. AB - In taenia preparations, depolarized by a K+-rich medium, Ca2+ caused contraction and cinnarizine (0.4-100 microM), trifluoperazine (2-100 microM) and verapamil (0.02-10 microM) caused concentration-dependent antagonism of Ca2+, displacing the Ca2+ log concentration-effect curve to the right and depressing the maximal response. Equieffective (IC75) antispasmogenic concentrations were selected. The antispasmogenic effects of verapamil were readily offset by removing the drug from the bathing fluid but those of the other drugs were not. The calcium antagonists (antispasmogenic IC75) were then tested for spasmolytic activity in tissues generating tension in response to the EC80 of Ca2+. Verapamil was more effective in producing spasmolysis than cinnarazine or trifluoperazine. In skinned taenia preparations, verapamil (100 microM) did not inhibit Ca2+-induced contractions. High concentrations of cinnarizine (100 microM) and trifluoperazine (100 microM) inhibited Ca2+-induced activation of the contractile proteins. However, antispasmogenic IC75s from intact taenia were not able to produce this effect on skinned preparations. It is concluded that there are differences between calcium antagonists. The action of verapamil on intact taenia is mainly exerted on the plasma membrane. Cinnarizine and trifluoperazine act both on the plasma membrane and upon the intracellular contractile machinery. PMID- 2884293 TI - Albumin microspheres for intra-articular drug delivery: investigation of their retention in normal and arthritic knee joints of rabbits. AB - The retention of 131I-labelled albumin microspheres and microsphere-entrapped [131I]rose bengal was investigated in normal and experimentally arthritic knee joints of rabbits. Albumin microspheres were cleared slowly from the joint cavity and no significant difference was observed between normal and inflamed joints. Entrapment of rose bengal within albumin microspheres was found to delay the clearance of the drug from the joint when compared with a solution of rose bengal. In addition, the retention time for entrapped rose bengal was dependent on the degree of inflammation present. PMID- 2884294 TI - Anthelmintic properties of Polygonum glabrum. AB - A pure anthelmintic substance (PGA) has been isolated from the methanol-aqueous extract of the leaf of Polygonum glabrum Willd., a semi-aquatic Sudanese species of the family Polygonaceae. The antiparasitic in-vitro activity of several fractions isolated from the plant, has been examined comparatively with that of PGA. PGA also showed molluscicidal activity against Biomphalaria glabrata and Limnea truncatula Mull. Structural determination of PGA was attempted following data analysis of UV, IR, 13C NMR, 1H NMR and MS spectra and suggests that PGA is a terpenoid. PMID- 2884295 TI - Dissolution mechanism of tablets produced from coated lactose powder. AB - The use of the equation of Kitazawa et al in the analysis of the dissolution process of tablets produced from lactose powder coated with paraffin has suggested either an initial breaking of the tablets into particles that subsequently break down into smaller particles or a progressive breaking of the tablet into smaller particles. The former produces a change in rate constant from k1 to k2. PMID- 2884297 TI - Central muscarinic activation elicits compulsive drinking behaviour in the rat. AB - Injection of bethanechol into the lateral cerebral ventricle of the rat induces a marked increase in drinking, within 30 min from administration. The response is dose-related, maximal water intake (6.1 +/- 0.55 mL; mean +/- s.e.) occurring at 10 micrograms of bethanechol. Peripheral administration of the agonist (up to 3 mg kg-1 i.p.) fails to elicit drinking. Among several specific antagonists only antimuscarinic drugs produced a significant inhibition of the response, suggesting that the compulsive drinking behaviour in the rat is caused by activation of central muscarinic receptors. The drinking behaviour emerges as a reliable test to assess central muscarinic activity of both agonists and antagonists. PMID- 2884296 TI - Effects of applied load and particle size on the plastoelasticity and tablet strength of some directly compressible powders. AB - Correlations have been established between the particle size and packing fraction of microcrystalline cellulose, calcium phosphate dihydrate, corn starch and lactose, and the elastic recovery, stress relaxation, and tensile strengths of their tablets. PMID- 2884298 TI - Enhanced gastrointestinal absorption of drugs in rats pretreated with the synthetic immunomodulator, levamisole. AB - The effect of levamisole on drug absorption from the rat small intestine has been investigated by means of an in-situ recirculation technique. The absorption of salicylic acid, sulphanilamide and aminopyrine was significantly increased by the intraperitoneal administration of levamisole (2 mg) 1 day before the absorption studies, but there was no significant effect on absorption from the small intestine of indomethacin, bromthymol blue, sulphafurazole (sulfisoxazole), quinine, sulphanilic acid, phenol red (phenolsulfonphthalein), L-tryptophan and fluorescein isothiocyanate-dextrans. The effect of levamisole on the absorption from the small intestine of salicylic acid was marginally dose- and time dependent, the maximal effect being observed after pretreatment with 2 mg of levamisole 1 day before the absorption studies. Sulphanilamide, similarly, was better sorbed from the small intestine and also from the stomach in the presence of levamisole. The intraperitoneal administration of levamisole may influence the absorption of some low molecular weight drugs from the gastrointestinal tract. PMID- 2884299 TI - 1-(o-Methoxyphenyl)piperazine is a metabolite of drugs bearing a methoxyphenylpiperazine side-chain. AB - Drugs bearing an o-methoxyphenylpiperazine (oOCH3PP) moiety in the side-chain of their molecule may form oOCH3PP during biotransformation in-vivo in the rat. This has been verified by combined gas chromatography-mass spectrometry of urine from rats given orally a series of relatively new o-methoxyphenylpiperazine substituted derivatives. The metabolite is reported to be biochemically and pharmacologically active and therefore its formation may have pharmacological significance, at least for derivatives undergoing extensive cleavage of the arylpiperazine side-chain. PMID- 2884300 TI - Effect of pyridoxine on prostaglandin synthesis in rabbit kidney medulla slices. AB - Pyridoxine stimulated the generation of prostaglandin E2 in rabbit kidney medulla slices. Moreover, pyridoxine in the presence of aspirin reduced the release of linoleic acid, but enhanced the release of arachidonic acid from the medulla slices as compared with aspirin alone, indicating that the enhancement of prostaglandin E2 formation elicited by pyridoxine may be ascribed to an increased conversion of linoleic acid to arachidonic acid. These results suggest that pyridoxine can be an important modulating factor in prostaglandin synthesis by the kidney. PMID- 2884301 TI - Selectivity and specificity for alpha 1-adrenoceptor blocking activity of R(-)- and S(+)-YM-12617 orally administered to pithed, spontaneously hypertensive rats. AB - The selectivity and specificity for alpha 1-adrenoceptor blocking activity of the optical isomers of YM-12617 have been examined in pithed, spontaneously hypertensive rats. R(-)-YM-12617 and prazosin (1 mg kg-1 p.o.) produced 360- and 88-fold rightward shifts, respectively, of the dose-response curve of control to phenylephrine, whereas S(+)-YM-12617 (1 mg kg-1 p.o.) failed to cause a shift. Based on dose ratio, R(-)-YM-12617 was 320 times more potent as an alpha 1 adrenoceptor antagonist than S(+)-YM-12617. This potency ratio corresponded to that formed in an in-vitro study. Both R(-)- and S(+)-YM-12617 hardly affected the UK-14304, angiotensin II, vasopressin and isoprenaline dose-response curves. These results suggest that R(-)-YM-12617 exerted selective alpha 1-adrenoceptor blocking activity and its activity was specific for alpha 1-adrenoceptors. PMID- 2884302 TI - Binding parameters and microbiological activity of macrolides, lincosamides and streptogramins against Staphylococcus aureus. AB - Parameters of erythromycin binding to Staphylococcus aureus were measured in vitro using an equilibrium method with [3H]erythromycin. The dissociation constant of the complex, erythromycin-S. aureus sensitive strain, was KD = 0.11 microM. The maximal binding, representing the density of binding sites was 14,847 molecules/cell. No binding was detectable on the constitutive resistant strain. Macrolides, streptogramins and lincosamides displaced bound [3H]erythromycin by a competitive process indicating that these compounds share common binding sites on the bacteria, i.e. 50 S ribosomal subunits. A good correlation (r = 0.99) was demonstrated between the corresponding inhibition constants (Ki) and the minimal inhibitory concentration. It is proposed that knowledge of the binding parameters provides a good indication of bacterial susceptibility and may serve as a useful adjunct in developing new compounds. PMID- 2884303 TI - Tamoxifen inhibits 5-lipoxygenase in human polymorphonuclear leucocytes. AB - Breast cancer patient survival is increased by tamoxifen, and we therefore need to understand how this drug exerts its effect. We describe a novel action of tamoxifen, the inhibition of LTB4 and 5-HETE production from [14C]-arachidonic acid by human polymorphonuclear leucocytes. PMID- 2884304 TI - Potentiation of contractile response and increase in tissue sodium content induced by aconitine in the guinea-pig vas deferens. AB - Aconitine potentiated the contractile response of the guinea-pig vas deferens and increased the tissue Na and Ca content. These effects were abolished in the presence of tetrodotoxin. These results suggest that aconitine causes an increasing Na+ permeability of the smooth muscle membrane to increase Ca2+ availability and thus induces potentiation. PMID- 2884305 TI - Calcitonin gene-related peptide activates non-adrenergic, non-cholinergic relaxations of the rat isolated duodenum. PMID- 2884306 TI - Tensile strength analysis of midpontic soldering. AB - A total of 120 three-unit fixed partial dentures were made by using a latex mold to produce uniform wax patterns. Four groups were used to compare the tensile strength of connectors with interproximal solder, midpontic vertical solder, midpontic diagonal solder, and a control of one-piece castings. Three different metals were tested and the tensile load required to fracture the samples as well as the fracture sites were recorded. The following was found: Soldering the interproximal connector area produced the weakest solder joints, regardless of metal tested, at p less than .001. There was no significant difference in the fracture loads between midpontic vertical soldering and midpontic diagonal soldering with all three metals at p less than .01. There was no significant difference in fracture loads between midpontic soldering and unit casting with all three metals at p less than .01. The extreme variations in fracture loads when soldering nickel-chrome-beryllium confirms the technique sensitivity of presoldering this alloy. PMID- 2884307 TI - Oxidation of glucose, ribose, alanine, and glutamate by Leishmania braziliensis panamensis. AB - The metabolism of [1-14C]- and [6-14C]glucose, [1-14C]ribose, [1-14C]- and [U 14C]alanine, and [1-14C]- and [5-14C]glutamate by the promastigotes of Leishmania braziliensis panamensis was investigated in cells resuspended in Hanks' balanced salt solution supplemented with ribose, alanine, or glutamate. The ratio of 14CO2 produced from [1-14C]glucose to that from [6-14C]glucose ranged from about two to six, indicating appreciable carbon flow through the pentose phosphate pathway. A functional pentose phosphate pathway was further demonstrated by the production of 14CO2 from [1-14C]ribose although the rate of ribose oxidation was much lower than the rate of glucose oxidation. The rate of 14CO2 production from [1 14C]glucose was almost linear with time of incubation, whereas that of [6 14C]glucose accelerated, consistent with an increasing rate of flux through the Embden-Meyerhof pathway during incubation. Increasing the assay temperature from 26 degrees C to 34 degrees C had no appreciable effect on the rates or time courses of oxidation of either [1-14C]- or [6-14C]glucose or of [1-14C]ribose. Both alanine and glutamate were oxidized by L. b. panamensis, and at rates comparable to or appreciably greater than the rate of oxidation of glucose. The ratios of 14CO2 produced from [1-14C]- to [U-14C]alanine and from [1-14C]- to [5 14C]glutamate indicated that these compounds were metabolized via a functioning tricarboxylic acid cycle and that most of the label that entered the tricarboxylic acid cycle was oxidized to carbon dioxide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884308 TI - The assessment of sympathetic nervous function in human stress research. AB - The methods currently available for measuring sympathetic nervous system activity in human stress research are critically reviewed. The advantages and limitations of catecholamine measurements in plasma and urine are considered. The contribution of skeletal muscle sympathetic activity to noradrenaline concentration in venous blood represents a serious drawback of this measure, and under many circumstances, urinary assay may reflect arterial catecholamine levels more accurately. The potential benefits of assessing noradrenaline clearance are described. Other methods of assessing sympathetic activity are also reviewed, including microneurographic techniques and the use of pharmacological blockade. General recommendations are given about the methods of greatest value in human stress research. PMID- 2884309 TI - Specific binding of L-[3H]-glutamic acid to rat substantia nigra synaptic membranes. AB - The specific binding of L-[3H]-glutamic acid (GLU) was investigated in synaptic membranes from rat substantia nigra. L-[3H]-GLU binding to the membrane preparations occurred in a reversible and saturable way. The specific binding was stimulated by the presence of CaCl2 and was reduced by freezing and thawing the membranes. Scatchard analysis of the saturation isotherms yielded a non-linear plot suggesting that the binding reaction does not occur through a simple bimolecular association. Assuming non-interacting binding sites, a high (KD1, 139 nM; Bmax1, 3.5 pmoles/mg protein) and a low (KD2, 667 nM; Bmax2, 15.1 pmoles/mg protein) affinity L-[3H]-GLU binding site were obtained. The kinetics of dissociation of bound L-[3H]-GLU was biphasic; the respective dissociation rate constant (k-1) being 0.20 min-1 and 0.013 min-1. A series of amino acid receptor agonists and antagonists were tested as inhibitors of L-[3H]-GLU specific binding. Quisqualic acid, L-GLU and D-alpha-aminoadipate (D-alpha-AA) were the most potent inhibitors. DL-2-amino-4-phosphonobutyrate (APB), N-Methyl-D aspartate (NMDA) and D-GLU were moderate inhibitors, whereas diaminopimelic acid (DAPA) and glutamate diethyl ester (GDEE) exhibited the lowest relative potency. Kainic acid (KA), gamma-aminobutyric acid (GABA) and bicuculline were not able to modify at any concentration used the specific binding of L-[3H]-GLU. These data demonstrate the presence of specific GLU binding sites in synaptic structures at substantia nigra level and support the idea that excitatory amino acids may play a role in synaptic transmission in this brain region. PMID- 2884310 TI - The binding of agonists and antagonists to rat lung beta-adrenergic receptors as investigated by thermodynamics and structure-activity relationships. AB - Interaction of several agonists and antagonists with the relevant beta receptor were studied in vitro using rat lung membranes as beta-adrenergic receptor source. The influence of temperature, between 4 degrees C and 37 degrees C, on the ability of beta-adrenergic agonists and antagonists to displace (-) [125I]iodocyanopindolol from beta-adrenergic receptors was checked. Thermodynamic parameters were calculated from the Kj values thus obtained. Lipophilicity of the twenty molecules was also measured using a RP-HPLC method. The results obtained show: the density of receptors was not affected by the temperature but their affinity for the twenty agonists and antagonists increased with decreasing temperature; the binding of agonists is enthalpy driven while that of antagonists is entropy driven, with the exception of the lipophilic agonist dobutamine; a single relationship between entropy and lipophilicity exists for all twenty compounds and would suggest that molecular structure and physicochemical properties account for the thermodynamics of binding. PMID- 2884312 TI - Synthesis of a series of compounds related to betaxolol, a new beta 1 adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases. AB - A series of para-substituted phenoxypropanolamines has been synthesized and tested for beta-adrenoceptor blocking activity. Some derivatives (8, 11, 12, 20, 21) exhibited greater in vitro potency than the reference drugs metoprolol and propranolol. This series, in contrast to propranolol but similar to metoprolol, possesses cardioselectivity. The 3-[p-[(cycloalkylmethoxy)ethyl]phenoxy]-1 substituted-amino-2-prop anol derivatives 8 (cyclopropylmethoxyethyl: betaxolol) and 11 (cyclobutylmethoxyethyl) produced antihypertensive effects in spontaneously hypertensive rats. Betaxolol (Kerlon, 8) was found to exhibit an appropriate preclinical pharmacological and human pharmacokinetic profile (elevated oral bioavailability and prolonged plasma half-life) for the treatment of chronic cardiovascular diseases such as hypertension and angina. PMID- 2884311 TI - Radioautographic localization and regulation of the insulin receptors in rat testis. AB - Luteinizing hormone (LH) is involved in maintenance of the insulin receptor in rat Leydig cells. In the cryptorchid model, spontaneous LH elevation increases insulin binding in Leydig cell membrane; this result is confirmed by the number of insulin receptors determined by radioautography. Administration of testosterone or LH-RH to control or cryptorchid rats lower insulin binding in testis membranes indicating the key role of LH. Isolated Leydig cells respond in vitro to LH by increasing their insulin binding. Localization and specificity of this binding has been studied by radioautography and we have demonstrated the preferential localization of insulin receptor in Leydig cells vs tubular cells. We conclude that insulin plays a synergistic role with LH on steroidogenesis via a specific membrane receptor which number appears modulated by pituitary LH. PMID- 2884313 TI - Conformationally defined adrenergic agents. 5. Resolution, absolute configuration, and pharmacological characterization of the enantiomers of 2-(5,6 dihydroxy-1,2,3,4-tetrahydro-1-naphthyl)imidazoline: a potent agonist at alpha adrenoceptors. AB - (+/-)-2-(5,6-Dimethoxy-1,2,3,4-tetrahydro-1-naphthyl)imidazoline has been resolved into its (+) and (-) enantiomers, and the absolute configuration was established by single-crystal X-ray diffraction studies. The more active isomer has been assigned the R absolute configuration. Cleavage of the respective (+)- and (-)-dimethyl ethers with boron tribromide provided the corresponding (+)- and (-)-2-(5,6-dihydroxy-1,2,3,4-tetrahydro-1-naphthl)imidazoline hydrobromides and these were pharmacologically characterized. In various preparations, the R enantiomer has been shown to be an extremely potent alpha agonist with preferential activity at the alpha 2-adrenergic receptor. PMID- 2884314 TI - Psychotropic agents: synthesis and antipsychotic activity of substituted beta carbolines. AB - A series of novel substituted beta-carbolines was synthesized and tested for potential antipsychotic activity. Several compounds displayed moderate antipsychotic activity in vitro and in vivo as determined by relevant receptor binding assays and behavioral tests. The effect of substituents on antipsychotic activity was examined. The beta-carbolines 10 and 19 containing 2-(2 pyridinyl)ethyl and 2-(2-quinolinyl)ethyl side chains were the most potent analogues, blocking discrete trial conditioned avoidance responding in rats with AB50's of 23 and 10 mg/kg, respectively. Both showed moderate activity at the D2 receptor sites, but they lacked oral activity. In contrast, the beta-carboline 13 containing the 4-(4-pyridinyl)butyl side chain exhibited oral activity in the discrete trial conditioned avoidance screen with an AB50 of 31 mg/kg. Most compounds did not antagonize apomorphine-induced stereotyped behavior, which is indicative of low potential for extrapyramidal side effect (EPS) liability. PMID- 2884316 TI - 2,4-Diamino-6,7-dimethoxyquinazolines. 2. 2-(4-Carbamoylpiperidino) derivatives as alpha 1-adrenoceptor antagonists and antihypertensive agents. AB - A series of 4-amino-2-(4-carbamoylpiperidino)-6,7-dimethoxyquinazolines (2) were synthesized and evaluated for alpha-adrenoceptor affinity and antihypertensive activity. These compounds displayed high binding affinity (Ki, 10(-9)-10(-10) M) and selectivity for alpha 1-adrenoceptors in vitro, and 12, 14, 21-26, and 29 showed similar potency to prazosin. Compounds 26 and 28 were also shown to be competitive antagonists of the postjunctional, vasoconstrictor action of norepinephrine with no significant activity at prejunctional alpha 2-sites. The high binding affinity for series 2 is rationalized in terms of enhanced basicity of the quinazoline nucleus (pKa's: 12, 7.38; 26, 7.53; prazosin, 6.8) and hydrophobic interactions of the carbamoyl substituents. Molecular mechanics calculations and computer-assisted superimposition suggest that the quinazoline 2 substituents in prazosin and 2 occupy the alpha 1-adrenoceptor site in different manners. Antihypertensive activity was evaluated after oral administration (5 mg/kg) to spontaneously hypertensive rats, and 11, 15, 21, 22, and 26 displayed sustained prazosin-like efficacy at the 6-h time point. The high alpha 1 adrenoceptor affinity demonstrated by series 2 in vitro suggests that these marked, and prolonged, falls in blood pressure result from selective blockade of the alpha 1-mediated vasoconstrictor effects of norepinephrine. PMID- 2884317 TI - Host-feeding patterns of Argentine mosquitoes (Diptera: Culicidae) collected during and after an epizootic of western equine encephalitis. PMID- 2884315 TI - 2-Amino- and 2-guanidino-1,2,3,4-tetrahydro-1,4-epoxynaphthalenes as conformationally defined analogues of alpha-adrenergic agents. AB - The exo- and endo-2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-1,4 epoxynaphthalenes++ + (3b and 4b, respectively) were prepared and evaluated as conformationally defined analogues of the alpha 1-agonist methoxamine. Only compound 3b exhibited significant alpha 1-agonist activity in the field stimulated rat vas deferens assay. Since 3b closely approximates the antiperiplanar form of (1R,2S)-(-)-erythro-methoxamine, the results suggest that methoxamine interacts with the alpha 1-adrenoceptor in the trans extended form. The exo-guanidino derivative 5 was found to be a partial alpha 1-agonist. Among the exo- and endo-2-amino-1,2,3,4-tetrahydro-1,4-epoxynaphthalenes (3a and 4a, respectively) prepared as rigid analogues of norephedrine, compound 3a possessed agonist activity at both alpha 1- and alpha 2-adrenoceptors, whereas 4a was inactive at either receptor. PMID- 2884318 TI - Electrophoretic comparison of the malic enzyme in Japanese mosquito (Diptera: Culicidae) larvae. PMID- 2884320 TI - Attitudes towards predictive testing in Huntington's disease: a recent survey in Belgium. AB - After the publication of evidence of the existence of a DNA polymorphism closely linked to the gene for Huntington's disease, attitudes towards predictive testing for Huntington's disease were evaluated in Belgium in a group of persons who are at risk for the disease and in a smaller group of their partners. The percentage of persons at risk who planned to take the test was smaller than in many previously published studies. Our results revealed a lack of association between the intention to take the test and social or demographic variables. Specific attention was paid to the difference in intention between a person at risk and his or her partner and to the opinions about the way the decision to take the test should be made. PMID- 2884321 TI - Demonstration by immuno-electronmicroscopy of antigenic heterogeneity among P fimbriae of strains of Escherichia coli. AB - The identification of P fimbriae on urinary strains of Escherichia coli isolated from urine was made by observation of the patterns of mannose-resistant and eluting haemagglutination of erythrocytes of seven animal species (and including those of human p phenotype), and by haemagglutination-inhibition tests with hydatid-cyst fluid known to contain an analogue of P-fimbrial receptor. In tests with five different, pure P-fimbrial antisera prepared in rabbits, agglutinin titres of 37 P-fimbriate strains revealed differences in their reactivity; immuno electronmicroscopy studies with the same five antisera showed that P-fimbriate strains were markedly different in the extent to which their P fimbriae were coated with antibody. The antigenic heterogeneity observed among P fimbriae is discussed with regard to the development of P-fimbrial vaccines. PMID- 2884322 TI - Pili on Gardnerella vaginalis studied by electronmicroscopy. AB - Fourteen recently isolated strains and two laboratory strains of Gardnerella vaginalis were examined by electronmicroscopy for the presence of pili. All strains isolated recently from both men and women were heavily pilated. In contrast only a few pili were seen on organisms of the two laboratory strains, with many of the organisms having no pili. The importance of multiple subculture in this loss was supported by the observation that the degree of pilation of one freshly isolated strain decreased on repeated subculture. Other findings suggested that this was probably due to gradual loss of pili and not to selection of organisms that were non-pilate originally. PMID- 2884319 TI - Molecular genetics of human chromosome 21. AB - Chromosome 21 is the smallest autosome, comprising only about 1.9% of human DNA, but represents one of the most intensively studied regions of the genome. Much of the interest in chromosome 21 can be attributed to its association with Down's syndrome, a genetic disorder that afflicts one in every 700 to 1000 newborns. Although only 17 genes have been assigned to chromosome 21, a very large number of cloned DNA segments of unknown function have been isolated and regionally mapped. The majority of these segments detect restriction fragment length polymorphisms (RFLPs) and therefore represent useful genetic markers. Continued molecular genetic investigation of chromosome 21 will be central to elucidating molecular events leading to meiotic non-disjunction and consequent trisomy, the contribution of specific genes to the pathology of Down's syndrome, and the possible role of chromosome 21 in Alzheimer's disease and other as yet unmapped genetic defects. PMID- 2884323 TI - Evidence for the transit of aminopeptidase N through the basolateral membrane before it reaches the brush border of enterocytes. AB - In vivo pulse-chase labeling of rabbit jejunum loops was used in conjunction with subcellular fractionation and quantitative immunoprecipitation to determine whether or not the newly synthesized aminopeptidase N transits through the basolateral membrane before it reaches the apical brush border, its final localization. The kinetics of the arrival of the newly synthesized enzyme in the Golgi complex, basolateral and brush border membrane fractions strongly suggest that on leaving the Golgi aminopeptidase N is transiently integrated into the basolateral domain before reaching the brush border. PMID- 2884324 TI - Prescribing in a hospital for the mentally retarded. PMID- 2884325 TI - The rudimentary gene of Drosophila melanogaster encodes four enzymic functions. AB - We have determined the 7168 nucleotide DNA sequence corresponding to the messenger RNA of the rudimentary gene of Drosophila melanogaster. By sequence comparison with genes involved in the pyrimidine pathway of prokaryotes and lower eukaryotes, we conclude that the rudimentary gene encodes four enzymically different functions. Each function is restricted to a specific coding domain but in an order different from that previously defined by genetic data. We have found that the corresponding mammalian gene, the CAD gene, exhibits a similar functional organization, and we propose schemes for the evolution of the corresponding coding sequences. PMID- 2884326 TI - A case of MAO inhibitor/MDMA interaction: agony after ecstasy. AB - After ingesting 3,4-methylene-dioxy-methamphetamine (MDMA) and the monoamine oxidase (MAO) inhibitor phenelzine, a 50 year old male developed marked hypertension, diaphoresis, altered mental status, and hypertonicity lasting 5-6 hours. This clinical course is typical of interaction between MAO inhibitors and some sympathomimetics including amphetamines. Such interaction has not previously been described involving MDMA. Sympathomimetic-MAO inhibitor interactions can cause excessive release of endogenous bioactive amines (e.g. norepinephrine, serotonin). Hypertensive crisis, intracranial hemorrhage, hypertonicity, and severe hyperthermia have occurred due to sympathomimetic-MAO inhibitor interactions. MDMA shares structural and pharmacologic features with other agents capable of causing this interaction, and this case suggests that MDMA can cause significant toxicity in patients taking MAO inhibitors. PMID- 2884327 TI - Acute hallucinogenic reaction to carbinoxamine maleate. AB - A reaction to Rondec is reported. The patient presented with agitation and hallucinations and responded promptly to a trial of physostigmine. The clinical picture and prompt resolution of symptoms with physostigmine strongly suggest that the reaction was to the antihistamine component of the medication. PMID- 2884328 TI - Home advantage in soccer: a retrospective analysis. AB - The existence of home advantage has been established for all major professional team sports in England and North America. The advantage was found to be greatest in soccer, with the home team currently obtaining about 64% of all points gained in the English Football League. Home advantage has changed very little since the formation of the League in 1888 and there are only small variations between the four Divisions of the League. The advantage is less marked in local derbies, in the FA Cup and in nonprofessional competitions. It is greater in the European Cup and increases as the stages of the competition progress. The allocation of three points, instead of two, for a win in the Football League has not changed home advantage, but its effect has been greatly reduced in the GM Vauxhall Conference where an away win gains more points than a home win. The statistical evidence suggests that crowd support and travel fatigue contribute less to home advantage in soccer than do the less easily quantifiable benefits of familiarity with conditions when playing at home. Further possible explanations for the advantage are discussed in the light of findings in other sports. PMID- 2884329 TI - Depression of reticulo-ruminal motor functions through the stimulation of alpha 2 adrenoceptors. AB - Inhibition of the cyclical contractions of the reticulum and the rumen by detomidine (10-40 micrograms/kg, i.v.), xylazine (20-80 micrograms/kg, i.v.) and clonidine (2.5-10 micrograms/kg, i.v.) were compared in sheep and cattle housed individually in box stalls. Two alpha 2-adrenergic receptor blocking agents, tolazoline and yohimbine, were administered intravenously for prevention (0.1-0.4 mg/kg) or reversal (0.4-1.2 mg/kg) of these effects. Continuous recording of the reticuloruminal contractions and measurement of the volume of ruminal gas eliminated through the upper respiratory tract indicated that the three alpha 2 agonists inhibited the primary ruminal contractions associated with the reticular contractions. The occurrence of secondary ruminal contractions was also blocked in sheep, but only suppressed in cattle. The inhibition of reticulo-ruminal contractions was prevented or reversed competitively by the two alpha 2-blocking agents, suggesting an alpha 2-adrenoceptor mediation of the inhibition of cyclical motor activity of the reticulo-rumen. In contrast with tolazoline, yohimbine was unable to alleviate the accumulation of gas resulting from inhibition of the secondary ruminal contractions. PMID- 2884330 TI - Tissue-specific expression of human provirus ERV3 mRNA in human placenta: two of the three ERV3 mRNAs contain human cellular sequences. AB - Three polyadenylated RNAs, 9, 7.3, and 3.5 kilobases long, of a human endogenous retrovirus, ERV3, are abundant in human placental chorion, representing about 0.03 to 0.05% of the total mRNA. We characterized the structure of these mRNAs by Northern blot and S1 nuclease mapping analyses. We found that all three RNAs were spliced mRNAs that lacked 5.9 kilobases of proviral sequence, including the gag gene and most of the pol gene. In contrast to the transcription pattern usual for other retroviruses, the transcription pattern of the ERV3 provirus did not include a genome-length mRNA. All three of the ERV3 mRNAs initiated transcription at the same point in the 5' long terminal repeat (LTR) and contained identical splice junctions in the provirus. The 3.5-kilobase RNA was a typical subgenomic proviral mRNA, with its polyadenylation site in the 3' LTR. The two larger ERV3 mRNAs, however, extended through the polyadenylation site in the 3' LTR and were spliced at a second position approximately 370 nucleotides downstream from the 3' LTR. This finding suggests that when the ERV3 retrovirus integrated at this genomic locus in an ancestor of humans, it integrated within or adjacent to a cellular gene. PMID- 2884331 TI - Promoters and processing sites within the transforming region of bovine papillomavirus type 1. AB - The mRNAs present in bovine papillomavirus type 1 (BPV-1)-transformed C127 cells were studied by primer extension. The results show that two internal promoters are present in the E region of BPV-1 in addition to the previously identified promoter at coordinate 1 (H. Ahola, A. Stenlund, J. Moreno-Lopez, and U. Pettersson, Nucleic Acids Res. 11:2639-2650, 1983). One, located at coordinate 31, generated a set of mRNAs with heterogeneous 5' ends, which may encode the major transforming protein of BPV-1, the E5 protein. The second promoter, which is located at coordinate 39, generates colinear mRNAs which encode either the E4 protein or a truncated form of the E2 protein. Unlike the cottontail rabbit papillomavirus (O. Danos, E. Georges, G. Orth, and M. Yaniv, J. Virol. 53:735 741, 1985), BPV-1 appears to lack a separate promoter for expression of the E7 protein. The major splice sites in the transforming region (E region) of the BPV 1 genome were also identified by nucleotide sequence analysis. PMID- 2884333 TI - The birth of the blues: II. Blue movie. PMID- 2884332 TI - Insertion and truncation of c-myb by murine leukemia virus in a myeloid cell line derived from cultures of normal hematopoietic cells. AB - A retroviral insertion into the c-myb gene, which resulted in a 3' truncation, was found in an in vitro-derived myeloid cell line. The retroviral insertion occurred at precisely the same nucleotide at which another murine leukemia virus insertion occurred in an in vivo-induced myeloid leukemia. These findings suggest that comparable events may be required for the derivation of myeloid cell lines in vitro and for induction of myeloid leukemia in vivo. PMID- 2884334 TI - Somatostatin receptors as markers for endocrine tumors. PMID- 2884335 TI - [Influence of sevoflurane on the neuromuscular blocking effects of vecuronium and pancuronium]. PMID- 2884336 TI - [Diagnostic procedure of adult T-cell leukemia--comparison of methods to detect anti-ATLA]. PMID- 2884337 TI - [Effects of atrial natriuretic factor on cyclic GMP synthesis in rat vascular smooth muscle cells in culture]. PMID- 2884338 TI - Active transport of beta-adrenergic blocking agents in the anterior uvea of albino rabbit. AB - Transport of timolol and befunolol in the anterior uvea of the albino rabbit was studied in vitro. Also, the mode of timolol elimination from the living eye was investigated. The isolated iris-ciliary body incubated at 37 degrees C accumulated 14C-timolol and 14C-befunolol against the concentration gradient, and the tissue-to-medium ratio was 5.45 +/- 0.29 and 5.46 +/- 0.44, respectively. The accumulation of both drugs was significantly suppressed by incubation at 0 degrees C and also by pretreatment with ouabain or cyanine but not with probenecid. The relationship between the initial velocities of accumulation and medium drug concentrations conformed with saturation kinetics, indicating the presence of mediated transport of these drugs. The apparent Km was 1.08 X 10(-6) mole per liter for timolol and 8.00 X 10(-7) for befunolol, and the Vmax was 5.46 X 10(-9) mole per g per hour for timolol and 1.52 X 10(-8) for befunolol. A mixture of 14C-timolol and 3H-sucrose was injected into the center of the vitreous cavity of the living rabbit. Timolol was lost from the vitreous at a rapid rate of about 36% per hour, while sucrose was lost very slowly, at about 5% per hour. Thus it was thought that an energy-requiring carrier-mediated transport system is operative in the anterior uvea of the albino rabbit, and that this would account for the rapid removal of the beta-blockers out of the eye. PMID- 2884339 TI - Comparison of agonistic and antagonistic actions of guanabenz and guanfacin on alpha 1 and alpha 2-adrenoceptors in isolated smooth muscles. AB - The effects of guanabenz, guanfacine and clonidine on alpha-adrenoceptors were investigated in isolated rat vas deferens and rabbit aortic strip. All 3 drugs at low concentrations (10(-9)-10(-8) M) caused inhibition of twitch responses of the rat vas deferens induced by nerve stimulation. These effects were competitively antagonized by yohimbine. Guanfacine and clonidine at relatively high concentrations (10(-6)-10(-4) M) produced contractions of the rat vas deferens which were antagonized by prazosin. These contractile responses were not much affected by denervation. Prazosin-sensitive contractions by guanfacine and clonidine were also observed in the rabbit aortic strip, which were not affected by reserpine pretreatment. In both tissues, the intrinsic activity of guanfacine was almost identical to that of norepinephrine, whereas that of clonidine was less than one half. Guanabenz and clonidine showed a competitive antagonistic effect against norepinephrine and phenylephrine in both the rat vas deferens and rabbit aorta, the antagonisms being similar in potency. The results indicate that all 3 drugs are potent agonists on the presynaptic alpha 2-adrenoceptor. In contrast, on the postsynaptic alpha 1-adrenoceptor, guanfacine and guanabenz showed only agonistic and antagonistic actions, respectively, whereas clonidine exhibited partial agonistic characteristics. PMID- 2884340 TI - Antimuscarinic effects of antihistamines: quantitative evaluation by receptor binding assay. AB - Quantitative evaluation of antimuscarinic effects of antihistamines (H1- and H2 receptor antagonists) was carried out using a receptor-binding assay. The inhibition constants (Ki values) of twenty seven H1-receptor antagonists, one related antidepressant and three H2-receptor antagonists at H1-receptors and muscarinic receptors in the bovine cerebral cortex were determined. All the H2 receptor antagonists examined showed very low affinity for the muscarinic receptors. On the other hand, some H1-receptor antagonists (mequitazine, cyproheptazine, clemastine, diphenylpyraline, promethazine, homochlorcyclizine and alimemazine) had high affinity for the muscarinic receptors (Ki = 5.0-38 nM). Another group of H1-receptor antagonists (mepyramine, terfenadine, metapyrilen, azelastine, hydroxyzine and meclizine) had low affinity for the muscarinic receptors (Ki = 3,600-30,000 nM). Thus, a broad range of antimuscarinic potencies among the antihistamines was demonstrated. These results should provide helpful information with regard to the clinical and experimental use of antihistamines. PMID- 2884341 TI - Enzymatic study to characterize the slow reacting substance of anaphylaxis (SRS A) and leukotrienes. AB - Slow reacting substance of anaphylaxis (SRS-A) has been shown to be one of the major mediators in hypersensitive reactions and to be composed of leukotriene (LT) C4, LTD4 and LTE4. In the present study, we examined the properties of SRS-A released from sensitized guinea pig lungs by antigen and SRS released from rat peritoneal exudate cells and from human leucocytes by ionophore A23187 (0.5 and 0.2 microgram/ml, respectively). By the incubation with SRS-A, SRS and LTs with arylsulfatase (type V) in pH 5.7 buffered solution at 37 degrees C for 30 min, SRS-A and LTD4 were greatly inactivated and rat SRS was slightly inactivated, but human SRS and LTC4 were not inactivated at all. The same results were obtained when aminopeptidase was used in place of arylsulfatase. Moreover, when SRS-A, LTC4 and LTD4 were incubated with 0.02 mg/ml of gamma-glutamyltranspeptidase (gamma-GTP) pH 8.0 buffered solution at 37 degrees C for 30 min, the activities of SRS-A and LTD4 were slightly decreased, but those of SRS and LTC4 were obviously potentiated. On the other hand, incubation with a large amount of gamma GTP (0.2 mg/ml) a dose at which this enzyme preparation showed clear aminopeptidase activity, SRS-A, SRS, LTC4 and LTD4 were obviously inactivated. In addition, we found a peak of LTD4 in guinea pig SRS-A, that of LTC4 in human SRS, and that of LTC4 in rat SRS on high performance liquid chromatograms. From these results, we demonstrated that guinea pig lung SRS-A is mainly composed of LTD4, human leukocyte SRS is mainly LTC4, and rat peritoneal SRS is composed of both LTC4 and LTD4. The inactivation of LTD4 and SRS-A by arylsulfatase may be due to aminopeptidase contamination in the enzyme preparation. PMID- 2884342 TI - Spermatogenesis and peripheral spermatic venous plasma androgen levels in the unilateral cryptorchid dogs. PMID- 2884343 TI - Effect of 1 alpha,25-dihydroxyvitamin D3 on proliferation of activated T-cells and established human lymphotropic virus type I-positive T-cell lines. AB - The effects of 1 alpha, 25-dihydroxyvitamin D3 [1,25-(OH)2D3] on proliferation and de novo DNA synthesis were studied in the following established human leukemia cell lines: lymphoblastic T-cell lines HPB-ALL, CCRF-HSB-2, p12/lchikawa, and HPB-MLT; adult T-cell leukemia- (ATL) and human lymphotropic virus type I (HTLV-I)-infected T-cell lines HUT102, HUT-102B2, MT-1, MT-2, MJ, C2/MJ, KH-2, KH-2Lo, HPB-CTL-1, and ATN-C1; ATL-derived B-cell lines ATL-BK9 and ATL-BK10; lymphoblastic B-cell line Daudi; and myelocytic-monocytic lineage cell lines HL-60 and U937. 1,25(OH)2D3 inhibited proliferation and de novo DNA synthesis of phytohemagglutinin-P-activated T-cells and certain established HTLV I-positive T-cells. However, it did not inhibit immature lymphoblastic T- and B cells or ATL-derived B-cells. The degree of inhibition depended on the dose of 1,25(OH)2D3 and the heterogeneity of the established HTLV-I-positive T-cells. KH 2 and subclone KH-2Lo were markedly inhibited, and HPB-CTL-1 was moderately inhibited. Marked inhibition of DNA synthesis in KH-2Lo cells was observed in the proliferative phase of the cell cycle. No inhibition of KH-2Lo proliferation or expression of interleukin-2 and transferrin receptor was noted after removal of 1,25(OH)2D3 from the culture medium. 1,25(OH)2D3 inhibited 12-O tetradecanoylphorbol-13-acetate (TPA)-induced multinucleated cell formation of various HTLV-I-positive T-cell lines and TPA-induced HTLV-I p19 expression in KH 2Lo cells. PMID- 2884344 TI - [Comparative evaluation of the results of conservative and surgical treatment of unstable angina at long-term follow-up]. AB - Two hundred patients with unstable angina were examined. Of those, 100 were on medication only, while another 100 had undergone aortocoronary shunting. Five year survival rate was higher, and the quality of life was better, in the surgical patients, as compared to conservative cases. PMID- 2884345 TI - [Experience with 5 years of drug therapy of ischemic heart disease patients with stable angina and stenosing atherosclerosis of the coronary arteries]. AB - The results of 5-year pharmacologic treatment of 234 coronary patients with stable angina of varying functional classes are reported. Coronarography detected stenosis of major coronary arteries in all cases; ventriculography demonstrated no disorders of left-ventricular contractility. Clinical improvement and stabilization occurred in 75.2% of patients, deterioration, in 24.8%. Of the latter group, nonfatal myocardial infarction occurred in 13.7%, and signs of heart failure developed in 9.8%. Repeat bicycle ergometry demonstrated increased or unchanged physical stress tolerance in 67.1%. Working capacity was intact after five years in 61.1%. Therefore, long-term medication of coronary patients with stable angina and normal left-ventricular contractility has proved efficient. PMID- 2884348 TI - [Effect of cooling and freezing on the microflora of water regenerated from a condensate of atmospheric vapor]. PMID- 2884347 TI - The role of endogenous noradrenaline in the beta-blocker withdrawal phenomenon- studies with cultured heart cells. AB - An in vitro model to evaluate the role of endogenous noradrenaline in the beta blocker withdrawal phenomenon is described: Beating chicken heart muscle cells (5000 beta 1-adrenoceptors/cell) and heart nonmuscle cells (3000 beta 2 adrenoceptors/cell) were cultured in serum-free, hormone-supplemented medium. Basal state, subtype selective down-regulation of beta-adrenoceptors by endogenous noradrenaline (decrease in receptor number, beta 1 more than beta 2) was simulated by addition of noradrenaline to the culture medium; chronic beta blockade was simulated by exposure of the cells for 3 days to various beta blockers (propranolol, no ISA; timolol, slight ISA; pindolol, strong ISA). Beta blocker withdrawal phenomenon--increased response in isoproterenol-induced cAMP production and positive inotropy--is correlated with the increase in the number of beta-adrenoceptors after withdrawal of the drugs. Propranolol induces a withdrawal phenomenon at every degree of noradrenaline-induced basal state down regulation of beta-adrenoceptors; in contrast, a withdrawal phenomenon by pindolol is only seen at a higher degree of beta-adrenoceptor down-regulation. In the presence of physiological noradrenaline concentrations pindolol affects beta adrenoceptor subtypes in a qualitatively different manner: the number of beta 1 adrenoceptors is increased, the number of beta 2-adrenoceptors is decreased. This finding demonstrates that the intrinsic sympathomimetic activity of nonselective beta-blockers can manifest itself only if the receptors are not strongly down regulated. As beta 2-adrenoceptors are present in a much less down-regulated state than beta 1, ISA mainly acts on beta 2-adrenoceptor subtype, thus, presenting a beta 2-"pseudo-selectivity" of ISA. PMID- 2884346 TI - [How many beta-receptor blockers does the physician need?]. PMID- 2884349 TI - Effect of histamine and histamine receptor antagonists on rat mesenteric microcirculation. AB - Histamine release adjacent to mesenteric arterioles under conditions of ischemia causes vasodilation and increases regional blood flow. This is presumably a protective mechanism which may be blocked by the use of H1 and H2 antagonists. Mesenteric arterioles of 29 rats were observed with intravital microscopy. Diameter and erythrocyte velocity were measured and arteriolar flow was calculated. Histamine was topically applied to the vessels under view in sequentially increasing concentrations (10(-7) to 10(-4) M). Following systemic injection of an H1 or H2 receptor antagonist or ibuprofen, the application of 10( 4) M histamine was repeated. Topical histamine caused vasodilation (122% of control; P less than 0.05) at 10(-4) M with a corresponding increase in erythrocyte velocity and calculated flow (118 and 177% of control, respectively; P less than 0.05 for each). The vasodilatory effects of histamine were blocked by systemic injection of histamine receptor antagonists (H1 + H2 greater than H1 greater than H2), while ibuprofen had no significant effect. In situations in which the gut is at risk for ischemia, the use of H1 and/or H2 receptor antagonists may seriously compromise the mesenteric microcirculation. PMID- 2884350 TI - Extra-adrenal paraganglioma and pulmonary chondroma: a case report and review of the literature. AB - This report describes the findings of an extra-adrenal paraganglioma and chondroma of the lung in an elderly man. Tissue analysis of the paraganglioma showed a high level of catecholamines, as well as the presence of somatostatin and small amounts of other peptide hormones. Immunoperoxidase staining demonstrated the distribution of peptide hormones in the tumor. This case illustrates two important points. First, it confirms the ability of paraganglionic tissue to secrete peptide hormones. Secondary, it adds yet another case to the unusual group of patients described by Carney (Carney JA: Cancer 43:374-382, 1979). PMID- 2884351 TI - Selective manipulation of neurohumoral control of the cardiac pacemaker by drugs given intrapericardially. AB - A technique of intrapericardial administration of beta-adrenoceptor and muscarinic cholinergic receptor antagonist drugs has been tested in conscious rabbits. Intrapericardial propranolol or atenolol (50 micrograms/kg) had the same effect on isoprenaline heart rate dose-response curves and on the sympathetic component of the arterial baroreceptor-heart rate reflex as did conventional, 5 fold greater, intravenous doses of the drugs. The action of intrapericardial propranolol was attributable to its (-)isomer. Intrapericardial propranolol (50 micrograms/kg) had little effect on ventricular contractility. Plasma levels of propranolol and atenolol after intrapericardial administration were, respectively, 7- and 40-fold less than after the usual intravenous doses. Intrapericardial hyoscine methyl bromide (10 micrograms/kg) abolished baroreflex vagal effects on heart rate as effectively as did the conventional, 5-fold greater, intravenous dose. The duration of receptor blockade by both classes of drugs when given intrapericardially was at least 2 hr. We conclude that the rapid diffusion of beta-adrenoceptor and muscarinic cholinergic receptor blocking drugs from the pericardial sac to receptors on the sinoatrial cardiac pacemaker, and their prolonged actions, provides a useful technique for preventing the actions of the sympathetic and vagus nerves, and of circulating catecholamines, on the chronotropic functions of the heart. PMID- 2884353 TI - Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. AB - Measurement of lactate dehydrogenase (LDH) activity released to the extracellular bathing media has been found to be a simple yet quantitative method for assessing glutamate mediated central neuronal cell injury in cortical cell culture. Extracellular LDH is both chemically and biologically stable; the magnitude of LDH efflux in the cultures correlates in a linear fashion with the number of neurons damaged by glutamate exposure. PMID- 2884352 TI - Amino acid neurotransmitters in postmortem human brain analyzed by high performance liquid chromatography with electrochemical detection. AB - In the present study we have developed a method of measuring putative neurotransmitter amino acids using high performance liquid chromatography (HPLC) with electrochemical detection. The assay had a sensitivity in the low pmol range and sample turnover time was 30 min. The postmortem stability of amino acids was examined in an animal model simulating human autopsy conditions. Aspartate concentrations increased 15% between 4 and 24 h postmortem while gamma aminobutyric acid (GABA) concentrations rose 35% by 4 h but were stable thereafter. Glutamate and taurine were stable at all time points. The assay has been used to examine concentrations of neurotransmitter amino acids in 15 patients without neurological or psychiatric disease. Results agree well with previous work and knowledge of amino acid neurotransmitter pathways. The current technique provides a reliable method for the study of amino acid transmitter abnormalities in neurological illness. PMID- 2884354 TI - [The delta phalanx]. PMID- 2884355 TI - [A new surgical method for the reconstruction of flexor tendon injuries of the hand: tendon and tendon sheath reconstruction by a two-phase operation]. PMID- 2884356 TI - [Comparative study of the blood circulation in reimplanted upper arms]. PMID- 2884357 TI - [Sepsis following burns (septic wounds, generalized sepsis)]. PMID- 2884358 TI - [Spinal anesthesia in operations on the lumbosacral region of the spine]. PMID- 2884359 TI - [Effect of immobilization on the bones]. PMID- 2884360 TI - [Sources of error and complications in Ender nailing of trochanteric fractures]. PMID- 2884361 TI - [Clavicular osteomyelitis as a complication of puncture of the subclavian vein]. PMID- 2884362 TI - [The place of pelvic osteotomy in the treatment of congenital hip dislocation]. PMID- 2884363 TI - [Significance of ventral spondylodesis in the management of cervical spine injuries]. PMID- 2884364 TI - [Experience with subtrochanteric osteotomy by hyperextension-abduction in the management of bilateral congenital hip dislocation]. PMID- 2884365 TI - [Affective disorders and neurotransmitters. Therapeutic implications]. PMID- 2884366 TI - [Salazopyrine in the treatment of rheumatoid arthritis]. PMID- 2884368 TI - Clonidine treatment for short stature. AB - 34 pubertal children with constitutional growth delay (CGD) were treated with clonidine orally twice a day. In 25 of the children the height velocity rose on clonidine treatment, and in 21 of them by more than 2 cm/yr during the first 6 months of treatment (mean [SD] growth increment 4.4 [0.5] cm/yr). Of the 22 who were treated for 12 months the increment in height velocity was maintained in 13 (3.4[0.4] cm/yr). Withdrawal of clonidine for 6 months did not stop the stimulatory effect of the drug on linear growth in 6 children, but in the other 8 children height velocities fell to pretreatment levels or below. In a few children reinstitution of clonidine for 2-4 months resulted in a new increment in height velocity. A high height standard deviation score and low growth velocity before treatment were predictive of a good growth response to clonidine. Clonidine did not induce noticeable side-effects. It may be a useful form of therapy for children with CGD. PMID- 2884367 TI - Influence of blood lead on the ability and attainment of children in Edinburgh. AB - The effect of blood-lead on children's ability and attainment was investigated in a sample of 855 boys and girls aged 6-9 years from eighteen primary schools within a defined area of central Edinburgh. The geometric mean blood-lead value was 10.4 micrograms/dl. In a stratified subsample, 501 children completed individual tests of cognitive ability and educational attainment from the British Ability Scales (BAS). An extensive home interview with a parent was also done. Multiple regression analyses showed a significant negative relation between log blood-lead and BAS combined score, number skills, and word reading when thirty three possible confounding variables were taken into account. There was a dose response relation between blood-lead and test scores, with no evidence of a threshold. The size of the effect was small compared with that of other factors. Lead at low levels of exposure probably has a small harmful effect on the performance of children in ability and attainment tests. PMID- 2884370 TI - The irritable oesophagus--a frequent cause of angina-like pain. AB - 33 patients with angina-like chest pain of oesophageal origin were investigated. In 8 (24%) the pain proved to be related to oesophageal motor disorders unaccompanied by gastro-oesophageal reflux; in 12 (36%) acid reflux contributed to chest pain; but in the remaining 13 (40%) identical chest pain episodes were due to various mechanisms including reflux without motor disorders, motor disorders without reflux, motor disorders without reflux but with positive acid perfusion test, and acid reflux without motility disorders but with positive edrophonium-stimulation test. These data strongly suggest that the mechanism of pain in these patients is related to irritability of the oesophagus. PMID- 2884369 TI - Polymorphic DNA marker on X chromosome and manic depression. AB - Heredity is an important factor in vulnerability to manic depression. A genetic linkage has been demonstrated between manic depression and coagulation factor IX at Xq27 with a TaqI polymorphism at the F9 locus in DNA samples from peripheral leucocytes of manic depressive probands and relatives in 10 informative families. Statistical analysis of the pedigrees gave a maximum lod score of 3.10 at a recombination fraction of 0.11, demonstrating a linkage between a manic depressive locus and the F9 locus in the Xq27 region. PMID- 2884371 TI - Low serum iron status and akathisia. AB - 26 patients were studied to assess the association between iron deficiency and akathisia. 13 akathisic patients were matched with 13 non-akathisic controls. Serum iron and percentage saturation were significantly decreased in the akathisic group, whereas total iron-binding capacity was significantly increased. A negative correlation between serum iron and akathisia rating (rs = -0.42) was also found. PMID- 2884372 TI - Increased monozygotic twinning rate after ovulation induction. AB - Multiple births after artificial induction of ovulation (AIO) are usually considered to be due to fertilisation of multiple ova. In the East Flanders Prospective Twin Study between 1978 and 1985 the frequency of zygotic splitting after AIO (1.2%) was significantly higher than the expected frequency (0.45%) among spontaneous twins and triplets. Moreover, after AIO the frequency of zygotic division was significantly higher in triplets than in twins. AIO seems to be the first identified biological mechanism influencing the monozygotic twinning rate. PMID- 2884374 TI - Treatment of myotonia. PMID- 2884373 TI - Bacterial pharyngitis. PMID- 2884375 TI - Detection of aortic regurgitation. PMID- 2884376 TI - Predictors of successful weaning in ventilated patients. PMID- 2884377 TI - Marrow transplantation for thalassaemia. PMID- 2884378 TI - Trends in mortality from cervical cancer in the Nordic countries: association with organised screening programmes. AB - Time trends in mortality from cervical cancer in Denmark, Finland, Iceland, Norway, and Sweden since the early 1950s were investigated in relation to the extent and intensity of organised screening programmes in these countries. In all five countries the cumulative mortality rates (0-74 years) fell between 1965 and 1982. In Iceland, where the nationwide programme has the widest target age range, the fall in mortality was greatest (80%). Finland and Sweden have nationwide programmes also; the mortality fell by 50% and 34%, respectively. In Denmark, where about 40% of the population are covered by organised programmes, the overall mortality fell by 25%, but in Norway, with only 5% of the population covered by organised screening, the mortality fell by only 10%. The results support the conclusion that organised screening programmes have had a major impact on the reduction in mortality from cervical cancer in the Nordic countries. PMID- 2884379 TI - Antibody response in primary human immunodeficiency virus infection. AB - The antibody response in 20 homosexual men with symptomatic primary HIV infection was studied with ten different antibody assays (enzyme-linked immunosorbent assays, indirect immunofluorescence assays, radioimmunoprecipitation [RIPA], and western blot). HIV antibodies were detectable by all the assays within 2 months after onset of illness. RIPA and western blot were more sensitive than the other assays--all serum samples obtained at 2 weeks and after were reactive. In all cases, the first serum sample reactive by RIPA precipitated gp160 whereas, by western blot, antibodies to p24 were first recognised. This study shows the necessity of including gp160 and p24 in any assay to detect early antibody response in primary HIV infection. 5 patients were studied by virus isolation. During the 2 first weeks after onset of symptoms, HIV was demonstrated in cell free plasma in all cases and, in 4 cases, also in peripheral blood mononuclear cells. Samples obtained later contained demonstrable infectious virus in only 1 of 4 cases. Thus a phase of viraemia precedes the antibody response in symptomatic primary HIV infection. PMID- 2884380 TI - Women doctors: a quarter-century track record. AB - According to Department of Health and Social Security figures for England and Wales, the number of women in medicine has risen substantially during the past 25 years. However, there has been little improvement in their career prospects. There is an urgent need for the present training programme and career structure to be made more flexible. PMID- 2884381 TI - Manganism in a neurological ethnic complex in Northern Australia. PMID- 2884383 TI - Management of exit-site infections during continuous ambulatory peritoneal dialysis. PMID- 2884382 TI - African Burkitt's lymphoma and an Epstein-Barr virus-enhancing plant Euphorbia tirucalli. PMID- 2884384 TI - Urokinase for recurrent CAPD peritonitis. PMID- 2884385 TI - Flash stimulation evoked potentials in diagnosis of chronic glaucoma. PMID- 2884386 TI - Birth control and paroxysmal nocturnal haemoglobinuria. PMID- 2884387 TI - High incidence of neural-tube defects in South India. PMID- 2884388 TI - C-myc expression in cervical cancer. PMID- 2884389 TI - Prognostic value of CSF lactate in cerebral malaria. PMID- 2884390 TI - Treatment of nocardiosis. PMID- 2884391 TI - Prostaglandins for peptic ulcer disease. PMID- 2884392 TI - Verapamil inhibits cyclosporin metabolism. PMID- 2884393 TI - Non-invasive method for measuring cardiac output after a full meal. PMID- 2884394 TI - Guidelines for mental patients rights. PMID- 2884395 TI - Primitive reflexes in psychiatry. PMID- 2884396 TI - Detection of heroin "body-packers" at Helsinki airport. PMID- 2884397 TI - Prescribing for drug-addicts. PMID- 2884398 TI - Boycotts and medicine. PMID- 2884399 TI - Diagnostic pathways. PMID- 2884400 TI - Topical minoxidil, scalp hair, and vasodilatation. PMID- 2884401 TI - Atrial natriuretic peptide concentrations during pregnancy. PMID- 2884402 TI - Group specific component and HIV infection. PMID- 2884403 TI - First trimester prenatal exclusion of tuberous sclerosis. PMID- 2884404 TI - Computed tomography of chest in diagnosis of miliary tuberculosis. PMID- 2884405 TI - Severe asthma after naproxen. PMID- 2884406 TI - Peripheral neuropathy and hyperthermia. PMID- 2884407 TI - Unusual opioid withdrawal syndrome. PMID- 2884408 TI - Effect of isotretinoin on survival of patients with myelodysplastic syndrome. PMID- 2884409 TI - Insulin and atheroma. PMID- 2884411 TI - Exclusion testing for Huntington's disease in pregnancy with a closely linked DNA marker. AB - 55 couples where one partner was at 50% risk of Huntington's disease (HD) were investigated with a DNA probe closely linked to HD, with a view to exclusion testing in a future pregnancy. In 3 of 9 pregnancies so far, HD was excluded in the absence of recombination. In 3 the risk was raised to around 50%, and in 2 exclusion tests were uninformative. The remaining couple changed their minds about termination of the pregnancy and the test was therefore judged inappropriate. PMID- 2884410 TI - Safety and efficacy of a recombinant DNA Plasmodium falciparum sporozoite vaccine. AB - A recombinant DNA Plasmodium falciparum sporozoite vaccine produced in Escherichia coli (FSV-1) was tested in doses of 10 micrograms to 800 micrograms protein in fifteen volunteers. No serious adverse reactions occurred. Antibodies that reacted with P falciparum sporozoite antigens by enzyme-linked immunoassay developed in twelve of the volunteers. The highest antibody titres induced were similar to those resulting from lifelong natural exposure to sporozoite-infected mosquitoes. Postimmunization serum samples from a majority of volunteers mediated the circumsporozoite (CS) precipitation reaction and inhibited sporozoite invasion of hepatoma cells in vitro. Serum from the three volunteers who received 800 micrograms doses reacted with the surface of sporozoites in an immunofluorescence assay. Six immunised volunteers receiving a fourth dose of FSV 1 and two non-immunised controls were challenged by bites of mosquitoes infected from cultured P falciparum gametocytes. Parasitaemia did not develop in the volunteer with the highest titre of CS antibodies, and parasitaemia was delayed in two other immunised volunteers. This study confirms that human beings can be protected by CS protein subunit vaccines and provides a framework for the further development and testing of more immunogenic sporozoite vaccines. PMID- 2884412 TI - First-trimester prenatal diagnosis for Huntington's disease with DNA probes. AB - Polymorphic DNA probes linked to the locus for Huntington disease (HD) were used for prenatal diagnosis of a 10-week fetus at 25% risk for the disease. The fetus proved to have a 48% risk of having inherited the HD mutation which was similar to that for the at-risk parent (50%). On this basis the parents elected to terminate the pregnancy. When appropriate family members are available and DNA studies are informative, prenatal diagnosis of HD with polymorphic DNA probes can determine the at-risk status of the fetus with 96% accuracy. PMID- 2884413 TI - Clinical, immunological, and virological effects of ampligen, a mismatched double stranded RNA, in patients with AIDS or AIDS-related complex. AB - 10 patients with the acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC), or lymphadenopathy syndrome (LAS) were given 200-250 mg ampligen, a mismatched double-stranded (ds) RNA with in-vitro antiviral activity against human immunodeficiency virus (HIV), twice a week for up to 18 weeks, without side effects or toxicity. In all 9 patients who were positive for HIV RNA in peripheral blood mononuclear cells before therapy, levels became undetectable between days 10 and 40 of the start of therapy. 6 of the 7 patients with ARC or LAS also showed a progressive reduction in HIV load as measured by co-culture assays. All 10 patients had augmentation of delayed-type hypersensitivity skin reactions. Other changes noted during ampligen therapy included an increase in or maintenance of numbers of helper-inducer T lymphocytes, improvements in HIV related symptoms, rises in titre of neutralising antibodies against HIV, and restoration of proper functioning of the natural lymphocyte antiviral dsRNA dependent (2'-5'-oligoadenylate/RNA-ase L) pathway. Thus, in the short term, ampligen seems to have the dual ability to restore immunological function and to control HIV replication. PMID- 2884414 TI - Desialylated transferrin as a serological marker of chronic excessive alcohol ingestion. AB - Partly desialylated transferrin was measured in the serum of subjects with chronic alcoholism, of patients with non-alcoholic-related steatohepatitis, diabetes, and other non-alcoholic liver diseases, and of healthy controls. In non alcoholic patients and controls the maximum desialylated transferrin expressed in relation to total transferrin was 1.5%. This value was exceeded in 18 (90%) of the 20 alcoholics. By contrast, gamma-glutamyl transferase was within the reference range in 9 of the alcoholics. PMID- 2884415 TI - 1,2-Dimethyl-3-hydroxypyrid-4-one, an orally active chelator for treatment of iron overload. AB - Subcutaneous desferrioxamine, though effective in preventing or reducing iron overload in transfusion-dependent refractory anaemia, is expensive and inconvenient. One potentially cheaper and orally active alternative is 1,2 dimethyl-3-hydroxypyrid-4-one (L1). This drug has been tested in three multiply transfused patients with myelodysplasia. Gelatin capsules were taken at doses ranging from 0.5 g to 3.0 g. Urinary iron excretion increased substantially in all three patients and in the one tested was equal to that achieved with comparable doses of subcutaneous desferrioxamine. The amounts of iron excreted were related to the dose of L1 administered and the iron load of the patients. The urinary excretion of zinc, magnesium, and calcium did not increase, and the drug was well tolerated. PMID- 2884416 TI - Nutrition in sport. PMID- 2884417 TI - Sulphasalazine: drug or pro-drug? PMID- 2884419 TI - Any advance on Dukes? PMID- 2884418 TI - Continuous extradural analgesia: catch-up or top-up? PMID- 2884420 TI - Hydronephrosis, renal obstruction, and renography. PMID- 2884422 TI - Prenatal diagnosis in albinism. PMID- 2884421 TI - A new prognostic classification of rectal cancer. AB - Only 60% of patients having radical surgery for rectal cancer are cured of their disease. The ideal system of classification would identify just two categories- the cured and those who will die of their disease. Specimens from 379 patients who had undergone radical surgery for rectal cancer more than 20 years ago were re-examined in order to identify discrete pathological variables that independently influence long-term survival. The selected variables were given weighted scores and the score range was divided to provide four prognostic groups. The model was tested on a second data set comprising 331 patients and gave similar results. The new prognostic classification is simple to use and is superior to staging by the method of Dukes because it places twice as many patients into groups that provide a confident prediction of clinical outcome. PMID- 2884423 TI - Junior doctors' hours: a 60-hour week is a real possibility. PMID- 2884424 TI - Phenylalanine content and total parenteral nutrition. PMID- 2884425 TI - Sugar and health. PMID- 2884426 TI - Acute necrotic myelopathy associated with influenza vaccination. PMID- 2884427 TI - Eradication of pertussis by vaccination. PMID- 2884428 TI - Diagnosing pneumococcal pneumonia. PMID- 2884429 TI - Hypothalamic syndrome in a woman with three sewing needles in the brain. PMID- 2884430 TI - Arthritis as manifestation of Lyme disease in England. PMID- 2884431 TI - Hypothyroidism and von Willebrand's disease. PMID- 2884432 TI - Sentinel tinnitus as symptom of acephalgic subarachnoid haemorrhage. PMID- 2884433 TI - Food allergy in steroid-resistant nephrotic syndrome. PMID- 2884434 TI - Intracardiac calcium. PMID- 2884435 TI - HIV and schizophrenia. PMID- 2884436 TI - HIV antigenaemia and virus isolation from plasma during primary HIV infection. PMID- 2884437 TI - Allografts as vectors of infection. PMID- 2884438 TI - Optic nerve gliomas in children with neurofibromatosis. PMID- 2884439 TI - Carbon monoxide poisoning presenting with focal epileptiform seizures. PMID- 2884440 TI - Aztreonam for cystic fibrosis patients who are hypersensitive to other beta lactams. PMID- 2884441 TI - CAPD peritonitis. PMID- 2884442 TI - Nocturnal adrenal suppression in children inhaling beclomethasone dipropionate. PMID- 2884443 TI - When should at-risk patients with thalassaemia be boosted with hepatitis B vaccine? PMID- 2884444 TI - Management of drug addicts. PMID- 2884445 TI - Medical manpower and student numbers. PMID- 2884446 TI - Needle exchange. PMID- 2884447 TI - Advertisement scrutiny. PMID- 2884448 TI - Useless drugs are not placebos. PMID- 2884450 TI - Traditional foods and diabetes. PMID- 2884449 TI - Passive smoking in adolescents: one-year stability of exposure in the home. PMID- 2884451 TI - Increased basal metabolic rate after sustained exercise in a cold environment. PMID- 2884452 TI - Serum osmolality gap in postoperative patients in intensive care. AB - The serum osmolality gap (OG), the difference between measured and predicted serum osmolality, was determined in 161 postoperative patients. A significantly increased OG was found in patients with failure of one or more organs, but rarely seen in those without organ failure. OG in non-survivors was significantly increased and sustained at a high level. Thus, the change in OG correlated with the severity of the patients' condition and their outcome. There was also a significant correlation between OG and hepatic cell function tests (arterial ketone body ratio and hepaplastin test). Analysis of non-aminoacid OG revealed that about 75% of the increased OG could be attributed to increased aminoacid concentrations, but that the remainder should be attributed to other undetermined solutes. Serial determination of OG provides information on metabolic abnormalities and prognosis of patients with progressively developing organ failure. PMID- 2884453 TI - Indium-111-labelled granulocyte accumulation in respiratory tract of patients with bronchiectasis. AB - 18 patients with severe bronchiectasis and persistent purulent sputum production were investigated, by the use of gamma scans, between acute exacerbations of their symptoms to determine localisation and traffic of 111In-labelled granulocytes in the lungs. Labelled granulocytes appeared in the respiratory tract of 16 patients within 24 h of their injection. Uptake occurred almost exclusively in areas demonstrated by computed tomography (CT) to be bronchiectatic. However, 111In uptake was not demonstrated in 21 of the 55 segments showing bronchiectasis on CT, and these were therefore thought to be not actively inflamed. The whole-body loss of radioactivity up to 4-7 days following injection of the labelled cells ranged from 0 to 53% and correlated with 24 h purulent sputum volume (r = 0.45, p less than 0.01) and with CT extent of moderate and severe bronchiectasis (r = 0.40, p less than 0.05), but not with overall CT extent of bronchiectasis, age, forced expiratory volume in one second, or duration of purulent sputum production in years. PMID- 2884454 TI - Prevention of rejection of kidney transplants by monoclonal antibody directed against interleukin 2. AB - The effect of 33B3.1, a rat IgG2a monoclonal antibody (MAb) directed against interleukin 2 receptors on activated T lymphocytes, was studied during the first two weeks after transplantation in an attempt to prevent rejection in primary, cadaveric, kidney transplant recipients. 9 patients received 5 mg 33B3.1 daily by intravenous infusion for 14 days (group A) and 18 received 10 mg daily (group B). Both groups also received prednisone and azathioprine. In threatened rejection, rescue treatment consisted of anti-thymocyte globulin (ATG). 33B3.1 was well tolerated, with mild fever during the first 2 days being the most common side effect. 3 patients in group A had a reversible acute rejection episode before day 14, whereas only 1 patient in group B had reversible rejection. 20 of 30 historical control patients (prednisone/azathioprine) and 2 of 55 patients previously treated with ATG had a rejection episode in a similar period after transplantation. Trough levels of 33B3.1 in the blood ranged from undetectable to 1.6 micrograms/ml in group A and from 0.3 to 9 micrograms/ml in group B. Most patients had antibodies against 33B3.1 by the end of treatment. PMID- 2884455 TI - Trial of an attenuated bovine rotavirus vaccine (RIT 4237) in Gambian infants. AB - A randomised, controlled trial of bovine rotavirus vaccine was undertaken in Gambian infants. Three doses were administered, from the age of ten weeks, concurrently with oral or killed polio vaccine. Prevaccination rotavirus neutralising antibody levels were high. 84/185 infants (45%) showed an increase in neutralising antibody titre after receiving rotavirus vaccine, compared with 20/91 (22%) unvaccinated infants. Clinical rotavirus infection was detected in 24/78 (31%) children in the rotavirus/oral polio group, 34/83 (41%) children in the placebo/oral polio group, and 23/92 (25%) children in the rotavirus/killed polio group, giving an overall vaccine efficacy of 33% (95% CI 4-53%). RIT 4237 did not appear to reduce the severity of clinical infections. Most cases (92%) were caused by rotaviruses with short RNA electropherotypes. Serological responses to rotavirus vaccination appeared unaffected by the concurrent administration of oral polio vaccine. Lower types 1 and 3 polio antibody levels were found in children who received oral polio and rotavirus vaccines but the differences were not statistically significant. PMID- 2884456 TI - Sexing the human pre-embryo by DNA-DNA in-situ hybridisation. AB - Human male pre-embryos were identified by means of DNA-DNA in-situ hybridisation with a commercially available DNA probe for Y-chromosome DNA. This method could lead to prenatal diagnosis of genetic disorders based on small numbers of cells that are not necessarily in division, such as cells obtained from a pre-embryo during the course of in-vitro fertilisation therapy. PMID- 2884457 TI - Myxoedema presenting with chiasmal compression: resolution after thyroxine replacement. AB - A 60-year-old woman presented with deteriorating vision. A computed tomography (CT) scan showed pituitary enlargement with chiasmal compression. Serum prolactin levels were normal but assessment of thyroid function showed a serum thyroxine level of 25 nmol/l (normal range 76-160 nmol/l) and a thyroid-stimulating hormone (TSH) level of 60 mU/l (normal range 0.5-5.0 mU/l). After 8 weeks of thyroxine replacement therapy (0.05 mg daily increasing to 0.1 mg daily after 3 weeks) the visual defects had resolved, serum TSH had fallen to 0.7 mU/l, and the CT scan showed pronounced reduction in the size of the pituitary gland. Measurement of TSH as well as prolactin is essential in all patients with pituitary enlargement, to avoid unnecessary pituitary surgery. PMID- 2884458 TI - The future of IPPNW. PMID- 2884459 TI - Life-threatening haemoptysis. PMID- 2884461 TI - Hypoprolactinaemia. PMID- 2884460 TI - Vibration arthrography. PMID- 2884462 TI - Anaesthesia for tonsillectomy. PMID- 2884463 TI - Alcohol and politics. PMID- 2884464 TI - Insecticide use and increased mortality in rural Central Luzon, Philippines. AB - In a major rice-growing area of the Philippines, widespread adoption of insecticides by farmers on smallholdings was followed by a 27% increase in mortality from causes other than trauma among economically active men. Several factors suggest a causal link: highly toxic chemicals have been used unsafely; mortality has increased only in the age and sex class occupationally exposed; mortality has decreased among unexposed urban men; specific mortality rates have increased for those conditions likely to be confused with insecticide poisoning and have decreased for others; and, both within and between years, the pattern of mortality among men has reflected that of insecticide use. The results suggest that the currently accepted figure of 10,000 deaths annually worldwide due to accidental intoxication with insecticides is a substantial underestimate. PMID- 2884466 TI - Non-A, non-B hepatitis surrogate testing of blood donations. PMID- 2884465 TI - What does a house-surgeon on call for the wards do? AB - This survey shows that the number and type of out-of-hours calls arising from general surgical inpatients in a service of 181 beds can be satisfactorily handled by an on-call house-surgeon, covering all the firms. The house-surgeon must have readily available support from the registrar on duty for the few difficult problems, and the firms must all do service ward-rounds on Saturdays and Sundays. This method of staffing at night and at weekends is economical but the work involved in the weekend rounds should be recognised. PMID- 2884467 TI - Ciprofloxacin for cholangitis after hepatic portoenterostomy. PMID- 2884468 TI - 14C-urea breath analysis, a non-invasive test for Campylobacter pylori in the stomach. PMID- 2884469 TI - ELISA for occult faecal albumin. PMID- 2884470 TI - Early decrease in atrial natriuretic peptide in acute myocardial infarction. PMID- 2884471 TI - Multiple sclerosis and gamma interferon. PMID- 2884473 TI - Muscle contraction headache. PMID- 2884472 TI - Sodium supplements, blood pressure, and calcium channel blocking drugs. PMID- 2884474 TI - First-aid for burns. PMID- 2884475 TI - Pulse oximetry, digital clubbing, and cystic fibrosis. PMID- 2884476 TI - Quality-adjusted life-years. PMID- 2884477 TI - Licensing work on IVF and related procedures. PMID- 2884478 TI - AIDS and student electives overseas. PMID- 2884479 TI - Surrogacy. PMID- 2884480 TI - Antifungal treatment of Candida peritonitis in CAPD patients. PMID- 2884481 TI - Combination of saline instillation with artificial ventilation damages bronchial surfactant. PMID- 2884482 TI - Echocardiography and septal thickness. PMID- 2884483 TI - Apomorphine infusion for motor fluctuations in Parkinson's disease. PMID- 2884484 TI - AIDS and the Gc protein. PMID- 2884485 TI - Brain death. PMID- 2884486 TI - Hypercholesterolaemia in newborn babies. PMID- 2884487 TI - Lowering blood pressure. PMID- 2884488 TI - Mechanism of membrane damage mediated by eosinophil major basic protein. PMID- 2884489 TI - Suramin and eosinophil degranulation and vacuolation in onchocerciasis. PMID- 2884490 TI - Acute adenovirus encephalitis diagnosed by prolonged intrathecal antibody production. PMID- 2884491 TI - International Physicians for the Prevention of Nuclear War. A new manner of thinking. PMID- 2884492 TI - Children and the threat of nuclear war. PMID- 2884493 TI - Consent to abortion on behalf of a mentally handicapped adult. PMID- 2884494 TI - Prospective study of radioimmunoassay for antibodies against neutrophil cytoplasm in diagnosis of systemic vasculitis. AB - The diagnosis and management of Wegener's granulomatosis and microscopic polyarteritis are complicated by the lack of specific diagnostic tests. The diagnostic performance of a solid-phase radioimmunoassay, which detects the autoantibodies against neutrophil cytoplasm present in these disorders, was assessed in a prospective study of patients with suspected vasculitis and/or rapidly progressive nephritis. The assay had a sensitivity and specificity of 96% when carried out in combination with a specific inhibition stage and indirect immunofluorescence staining of alcohol-fixed normal neutrophils. PMID- 2884495 TI - Autoantibodies to pituitary corticotropin-producing cells: possible marker for unfavourable outcome after pituitary microsurgery for Cushing's disease. AB - Circulating autoantibodies to human fetal pituitary cells were detected in 13 out of 51 patients who underwent transsphenoidal microsurgery for Cushing's disease. The absence of Fc receptors on human fetal pituitary corticotropin-producing cells allowed the detection of antibodies to these cells. In all the 13 patients, the antibodies were present before surgery, and 10 of them showed clinical and/or biochemical signs of incomplete cure of Cushing's disease after surgery. Only 3 out of 27 patients with a favourable outcome were antibody-positive. In all the antibody-positive patients, the antibodies were directed to corticotropin producing cells and in 8 patients also to luteinising hormone or human growth hormone producing cells. A non-antigen-specific adherence of antibodies to Fc receptors on corticotropin-cells was excluded by unchanged binding after preincubation of sections with purified rabbit Fc or Fc aggregates. The presence of pituitary corticotropin-cell antibodies in patients with Cushing's disease is associated with an unsuccessful outcome after transsphenoidal selective adenectomy. PMID- 2884496 TI - Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer. AB - In 135 primary breast cancers, there was a significant inverse relation between epidermal-growth-factor receptor (EGFR) and oestrogen receptor (ER) status, and a significant association with tumour size and poor differentiation. The relapse free survival and overall survival were significantly worse for patients with EGFR+ tumours compared with EGFR- tumours. Relapse-free survival and overall survival were also worse for patients with ER- tumours compared with ER+ tumours. Of the 71 ER- patients 28 were EGFR+ and 43 were EGFR-. The relapse-free and overall survival for ER- but EGFR+ patients were significantly worse than for "double-negative" patients. Moreover, relapse-free survival and overall survival for "double-negative" patients were similar to those for ER+ patients. Thus EGFR status divides the ER- population into good and poor prognosis subgroups. The presence of EGFR was the most important variable in the primary tumours for predicting relapse-free and overall survival. Multivariate analysis showed that EGFR status was the most important variable in predicting relapse-free and overall survival in lymph-node-negative patients, and the second most important variable in lymph-node positive patients. PMID- 2884497 TI - Do oncogenes determine clinical features in chronic myeloid leukaemia? AB - Oncogene abnormalities are thought to have a central role in some human malignant disorders, particularly Burkitt leukaemia/lymphoma and chronic myeloid leukaemia (CML). However, the extent to which specific oncogene changes determine the clinical features of these disorders is unknown. This question was studied in two groups of patients with CML negative for the Philadelphia (Ph) chromosome; one group showed clinical features typical of Ph-positive CML and the other group lacked such features. Molecular findings were compared with those of Ph-positive CML. In all ten patients there was evidence for rearrangement of the bcr (breakpoint cluster region) gene. In the four cases studied the c-abl proto oncogene was translocated to chromosome 22 and in five cases there was transcription of a chimeric bcr-abl mRNA. Thus, the molecular abnormality is the same in both groups of Ph-negative CML and identical to that in Ph-positive CML. Factors other than the bcr/c-abl rearrangement must underlie the clinical heterogeneity of CML. PMID- 2884498 TI - Changes in facial appearance during cyclosporin treatment. AB - Substantial changes in facial appearance developed in a group of children treated with prednisone and cyclosporin for immunosuppression after renal transplantation. In general, the children's features became coarse. There was thickening of the nares, lips, and ears, puffiness of the cheeks, prominence of the supraorbital ridges, and mandibular prognathism. The extent of the changes varied, but all eleven children followed up for more than 6 months from transplantation showed some of the changes. Patients treated with prednisone and azathioprine did not show any changes, clearly implicating cyclosporin in their aetiology. This dysmorphic syndrome along with the well-known hirsutism induced by cyclosporin may increase the risk of non-compliance with this immunosuppressive therapy. PMID- 2884499 TI - Lymphatic filariasis--tropical medicine's origin will not go away. PMID- 2884500 TI - Short-term intensive therapy for childhood non-Hodgkin lymphoma. PMID- 2884502 TI - The epidermal barrier. PMID- 2884501 TI - Idiopathic hypercalciuria--new thoughts on the phosphate connection. PMID- 2884503 TI - Transabdominal chorion villus biopsy: 100 consecutive cases. AB - A series of 100 transabdominal chorionic villus biopsies were carried out for maternal age (34 patients), fetal sexing (15), previous aneuploidy (21), biochemical analysis (5), gene-probe analysis (17), and oligohydramnios or fetal anomaly (6). 18 patients were over 14 weeks pregnant at the time of sampling. Tissue samples were obtained from 98 patients, including one set of twins. All 99 tissue samples proved adequate for laboratory diagnosis. Chromosome mosaicism was encountered in 4 cases (among direct preparation karyotypes in 1 case, between direct and cultured cells in 2 cases, and between chorion cells [both direct and cultured] and the fetus in 1 case). No patient miscarried but 1 had a stillbirth and 1, who had undergone transcervical biopsy before referral to our hospital, started to bleed before termination of pregnancy because of a diagnosis of cystic fibrosis. These data suggest that the transabdominal method of chorion biopsy will fulfil its theoretical and early promise. PMID- 2884504 TI - Phenytoin infusion in severe pre-eclampsia. AB - Intravenous phenytoin sodium was given as a high-dose infusion (10 X 8-18 mg/kg) for anticonvulsive prophylaxis to 2 eclamptic patients and to 24 patients with moderate to severe pre-eclampsia. There were no major maternal or neonatal side effects. Plasma phenytoin levels were within the therapeutic range (7-20 mg/l) at 30 min and 6 h after the infusion in all patients, and remained at a therapeutic level in 21 patients after 12 h. After a second dose of phenytoin in 19 patients, drug levels were within the therapeutic range at 24 h. PMID- 2884505 TI - Inadequate supplies of potassium and magnesium in relief food--implications and countermeasures. AB - Analyses of relief food used in Ethiopia showed that, because of food refinement, 6 out of 10 samples of cereals contained too little potassium and magnesium to cover daily needs. Malnutrition is often associated with gastrointestinal infections, which lead to further deficiency of these electrolytes. Potassium and magnesium are required for protein synthesis, growth, and tissue repair. Since protein supplies are often marginal, relief food should contain sufficient potassium and magnesium to allow optimum utilisation of dietary nitrogen sources. This may be achieved by using coarse qualities of cereals, by supplementing cereals with legumes, and by avoiding cooking procedures that extract these salts from the cereals. PMID- 2884506 TI - Ovarian failure after high-dose melphalan in adolescents. PMID- 2884508 TI - Multiple sclerosis on islands. PMID- 2884507 TI - Alpha 1-antitrypsin-related gene (ATR) for prenatal diagnosis. PMID- 2884510 TI - Management of non-convulsive status epilepticus. PMID- 2884509 TI - Multiple sclerosis and canine distemper on Key West, Florida. PMID- 2884511 TI - Safer acellular and whole-cell pertussis vaccines. PMID- 2884512 TI - Transient impairment of renal function after generalised seizures. PMID- 2884514 TI - AIDS publicity campaigns. PMID- 2884515 TI - HIV, bleach, and needle sharing. PMID- 2884513 TI - HIV envelope-CD4 interaction not inhibited by synthetic octapeptides. PMID- 2884517 TI - Retrovirus serology and Kawasaki syndrome. PMID- 2884516 TI - Kawasaki disease associated with HIV infection. PMID- 2884518 TI - Treatment of idiopathic orthostatic hypotension with xamoterol. PMID- 2884519 TI - Generic versus branded carbamazepine. PMID- 2884520 TI - Cervical cancer screening. PMID- 2884521 TI - Relevance of HPV-16 to laser therapy for cervical lesions. PMID- 2884523 TI - DNA diagnostic laboratories. PMID- 2884522 TI - Cultural barriers and the diagnostic process. PMID- 2884524 TI - Boycotts and medicine. PMID- 2884526 TI - Dose of intravenous IgG in primary hypogammaglobulinaemia. PMID- 2884525 TI - Melanoma surveillance and earlier diagnosis. PMID- 2884527 TI - Alopecia after immunoglobulin infusion. PMID- 2884528 TI - Minoxidil for male-pattern baldness. PMID- 2884529 TI - Exposure to benzodiazepines in utero. PMID- 2884530 TI - Long-term EEG monitoring in epilepsy. PMID- 2884531 TI - Tyrosinaemia type I and hypertrophic obstructive cardiomyopathy. PMID- 2884532 TI - Serological response to hepatitis delta virus in hepatitis D. PMID- 2884533 TI - Does "central" obesity predict coronary artery disease? PMID- 2884535 TI - Predictors of successful weaning in ventilated patients. PMID- 2884534 TI - Activated macrophages and cancer. PMID- 2884536 TI - Prevalence of gonococci lacking the 2.6 megadalton cryptic plasmid. PMID- 2884537 TI - Should healthy children be vaccinated against influenza? PMID- 2884538 TI - Rubella vaccination policy: a note of caution. PMID- 2884539 TI - Penicillin overdose and deafness. PMID- 2884541 TI - Rimcazole (BW 234 U) and regional monoamine concentrations in mouse brain. AB - Rimcazole (BW 234 U), a novel agent with antipsychotic potential, was administered i.p. (50 mg/kg) to adult male ICR mice 30 minutes before brain removal. Regional HPLC analysis of central monoamine levels showed no change in the DOPAC/DA ratio for any tissue as compared with values obtained from control saline treated animals. However, the MHPG/NE ratio was increased in the septum, striatum, hypothalamus and thalamus and there was a reciprocal decrease in the 5HIAA/5HT ratio in the septum. The data are consistent with a known lack of rimcazole affinity for dopamine receptors and indicate the involvement of alternate neurotransmitter systems in the actions of this drug. PMID- 2884540 TI - Identification of dynorphin 1-8 in human placenta by mass spectrometry. AB - The human placental villus tissue contains opioid receptors and peptides. The opioid peptides extracted from the villus tissue were fractionated using reverse phase high performance liquid chromatography and a radio-receptor assay. The presence of dynorphin 1-8 was corroborated by mass spectrometric production of (M + H) ion in the fast atom bombardment mode. This octa-peptide could be the natural ligand of the kappa opioid receptors present in the human placental villus tissue. PMID- 2884542 TI - Histamine and hepatic glutathione in the mouse. AB - A number of histamine receptor agonists and antagonists were utilized to study the effects of histamine on hepatocellular reduced glutathione (GSH) concentrations and the potential role of histamine as a mediator of morphine induced hepatic GSH depression. Administration of histamine, the H1-histamine receptor agonist thiazolylethylamine, the H2-histamine receptor agonist impromidine, or the histamine-releasing substance compound 48/80 resulted in no significant change in hepatic GSH concentrations. The H1-histamine receptor antagonist chlorpheniramine and the H2-histamine receptor antagonist ranitidine were also without significant effect on hepatic GSH and did not antagonize morphine-induced GSH depression. These observations indicate that histamine release following morphine administration does not play a significant role in the subsequent depletion of hepatic GSH. PMID- 2884543 TI - Growth hormone-releasing factor releases ACTH from an AtT-20 mouse pituitary tumor cell line but not from normal pituitary cells. AB - Corticotropin-releasing factor (CRF) and both human pancreatic growth hormone releasing factor (hp-GRF) and rat hypothalamic GRF (rh-GRF) stimulated ACTH release from neoplastic AtT-20 mouse pituitary tumor cells in a dose-dependent fashion, with CRF inducing a 10-fold increase and GRF a maximal increment of approximately one-half that of CRF. Neither rh-GRF nor hp-GRF induced ACTH release in normal anterior pituitary cells. Pretreatment with either dexamethasone or somatostatin prior to the addition of rh-GRF inhibited the increase in ACTH release. Both ovine CRF and rh-GRF stimulated adenosine 3,5 monophosphate production in AtT-20 cells. The weak but clearly discernible effect of GRF on ACTH release from AtT-20 cells may be due to an abnormality in the AtT 20 cell receptor. PMID- 2884544 TI - Absence of a 23 kd protein in testes of testicular feminization rat. AB - Cryptorchid testes of testicular feminization rats are very low in zinc in spite of normal zinc status of the animals. Analysis of the cytosol of the cryptorchid testes by gel permeation chromatography showed decreased zinc binding by proteins eluted at fractions corresponding to 30,000 dalton. Further analysis by sodium dodecylsulphate polyacrylamide gel electrophoresis indicated the absence of a protein with molecular weight of 23,000. PMID- 2884545 TI - Purification of IMP dehydrogenase from rat hepatoma 3924A. AB - IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme of de novo GTP biosynthesis and a promising target for cancer chemotherapy, was purified 4860 fold to homogeneity from rat hepatoma 3924A by a method including affinity chromatography in which IMP is bound to epoxy-activated Sepharose 6B. This affinity gel provided a specific elution of the enzyme with 0.5 mM IMP. The final enzyme preparation gave a single band with a molecular weight of 60,000 +/- 1000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis. PMID- 2884546 TI - Effect of inferior olive lesion on seizure threshold in the rat. AB - Cerebellar stimulation has been associated with anticonvulsant activity in several experimental seizure models. We examined the effect of destruction of cerebellar climbing fibers, by systemic administration of 3-acetylpyridine (3AP) or electrothermic lesion of the inferior olive, on seizures produced by various chemical convulsants in rats. We found that inferior olive lesioned rats had lower threshold to seizures induced by strychnine and brucine, both glycine antagonists. The dose response curve for strychnine seizure was shifted 2.5 times to the left in 3AP lesioned rats. No difference in seizure threshold was seen when picrotoxin, bicuculline or pentylenetetrazole PTZ) were used to produce seizures. Abnormal motor behavior (AMB) including myoclonus, backward movement and hyperextension, produced by all of the convulsants tested, was significantly aggravated in 3AP pretreated rats. The inferior olive-climbing fiber projection to the cerebellum appears to modulate seizures induced by inhibition of glycinergic neurotransmission. PMID- 2884547 TI - Positron emission tomography assessment of effects of benzodiazepines on regional glucose metabolic rate in patients with anxiety disorder. AB - Patients with generalized anxiety disorder (n = 18) entered a 21-day, double blind, placebo-controlled random assignment trial of clorazepate. Positron emission tomography with 18F-deoxyglucose was carried out before and after treatment. Decreases in glucose metabolic rate in visual cortex and relative increases in the basal ganglia and thalamus were found. A correlation between regional changes in metabolic rate and regional benzodiazepine receptor binding density from other human autopsy studies was observed; brain regions highest in receptor density showed the greatest decrease in rate. PMID- 2884548 TI - Effect of catecholamine on aldosterone release in isolated rat glomerulosa cell suspensions. AB - Effect of adrenergic activity on the adrenal steroidogenesis and the modulation by catecholamines of aldosterone release were studied in isolated rat adrenal cell suspensions. Isoproterenol, norepinephrine and epinephrine, but not dopamine, caused statistically significant increase in aldosterone release. Both prazosin (alpha 1 antagonist) and yohimbine (alpha 2 antagonist) suppressed the norepinephrine-induced aldosterone release in a dose dependent manner, respectively. Both atenolol (beta 1 antagonist) and ICI 118-551 (beta 2 antagonist) also blocked (-)-isoproterenol-induced aldosterone release in a dose dependent manner, respectively. Neither (-)-isoproterenol nor (+/-) norepinephrine at concentrations of 10(-6) M potentiated aldosterone release stimulated by angiotensin II or ACTH. These results suggest that catecholamines stimulate aldosteroidogenesis, but it appears unlikely that aldosterone release induced by ACTH or angiotensin-II is modulated by adrenergic stimulation. PMID- 2884549 TI - Behavioral effects of GABA agonists in relation to anxiety and benzodiazepine action. AB - A considerable body of biochemical and neurophysiological evidence implicates GABA in anxiety and in benzodiazepine action. The present article surveys the behavioral effects of GABA agonists and their interactions with drugs acting at the benzodiazepine receptor in animal anxiety paradigms. Certain GABA agonists, notably valproate, simulate many behavioral actions of benzodiazepines. Moreover, several behavioral studies of the interaction of GABA agonists with benzodiazepines support the hypothesis of a benzodiazepine receptor complex with one or more GABA, benzodiazepine and probably other binding sites. However, there are also a number of anomalous findings of GABA agonist action alone and in combination with benzodiazepines. It is argued that these paradoxical results can better be accounted for in terms of the receptor complex and the distribution of the drugs, rather than by suggesting that the anxiolytic actions of benzodiazepines are not mediated by GABA systems. The potential clinical usefulness of GABA agonists in anxiety is commented upon. PMID- 2884551 TI - Effects of moderate alcohol consumption on platelet aggregation, fibrinolysis, and blood lipids. AB - To investigate the effect of moderate alcohol consumption on blood constituents related to cardiovascular disease, 12 male volunteers consumed (instead of their usual alcoholic drinks) four different standardized amounts of red wine in addition to their habitual diet. Each dose was given to the subjects during a period of 5 weeks in a randomized order, all subjects receiving the four doses. They consisted of 0, 2, and 4 glasses/d, providing 0, 23, and 46 g alcohol/d as well as in "binge drinking" (14 glasses in the weekend, comparable to an average of 2 glasses/d). The results showed a clear dose-related response to the drinking for several blood constituents. Most marked was a decrease in the tissue-type plasminogen activator activity and to a lesser degree an increase in plasminogen levels. Collagen-induced platelet aggregation was reduced, affecting all parameters measured. Levels of HDL3-cholesterol, gammaglutamyltransferase, and urate showed a small but significant increase. No change was noted in the levels of alkaline phosphatase, alanine-aminotransferase, aspartate-aminotransferase, bile acids, folate, fibrinogen, the ADP-induced platelet aggregation, platelet secretion, or in hematologic values. The results are only partially in accordance with the presumed protective action of moderate drinking on the cardiovascular system and show a stronger response to the consumption of alcohol in coagulation and fibrinolysis factors than in blood lipids. PMID- 2884550 TI - Effect of long-term administration of an analog of growth hormone-releasing factor on the GH response in rats. AB - The effect of the repeated or continuous administration of an analog of GH releasing factor (GH-RF), D-Tyr-1, D-Ala-2, Nle-27, GH-RF(1-29)-NH2 (DBO-29), on the subsequent response to this peptide was investigated in pentobarbital anesthetized male rats. A sc administration of this analog induced a greater and more prolonged GH release than doses 10 times larger of GH-RF(1-29). The GH increase after sc injection of 10 micrograms/kg bw of the analog was greater than that induced by iv administration of 2 micrograms/kg bw of GH-RF(1-44). Pretreatment with 10 micrograms/kg bw of the analog did not affect the pituitary response to a strong stimulus (20 micrograms/kg bw) of GH-RF(1-44), 24 h later. Pretreatment with the analog in doses of 10 micrograms/kg bw, sc twice a day, 5 days per week for 4 weeks, significantly diminished the GH release in response to a sc injection of the analog (10 micrograms/kg bw), as compared to vehicle pretreated controls (P less than 0.01). On the other hand, a continuous sc administration of 0.4 micrograms/h of the analog to intact rats for 7 days did not result in a decrease in GH response to a sc injection of the analog (10 micrograms/kg bw). Since the rats injected repeatedly with the analog for 4 weeks still showed a marked, although somewhat reduced response, analogs of this type may be useful clinically. PMID- 2884552 TI - Catabolic effects of thyroid hormone excess: the contribution of adrenergic activity to hypermetabolism and protein breakdown. AB - Although patients with thyrotoxicosis improve clinically after treatment with beta-adrenergic blocking drugs, it has never been established whether the hypermetabolism and body protein wasting caused by thyroid hormone excess are actually mediated by adrenergic mechanisms. To evaluate this issue, we measured basal energy expenditure, epinephrine-stimulated calorigenesis, and leucine kinetics (an index of body protein catabolism) in six normal volunteers before and after triiodothyronine (T3) administration (150 micrograms/d for 1 week). Serum T3 rose nearly threefold (P less than 0.001) during T3 administration, producing significant increases in basal metabolic rate (21%, P less than 0.001), nitrogen excretion (45%, P less than 0.001), and leucine flux (45%, P less than 0.01). In response to epinephrine infusion, the absolute rise in metabolic rate above basal was 57% greater in the thyrotoxic condition (P less than 0.02). Although beta-adrenergic blockade with intravenous propranolol totally abolished the calorigenic response to epinephrine, it had no detectable effect on either the accelerated basal metabolic rate or the augmented body protein catabolism caused by thyroid horomone excess. Our data suggest that in the basal, resting state, the increased metabolic rate and accelerated protein breakdown caused by thyroid hormone are not adrenergically mediated. However, under nonbasal conditions (when sympathetic activity is stimulated), enhanced responsiveness to catecholamine calorigenesis may exaggerate the hypermetabolic state and thereby contribute to weight loss and other clinical manifestations of thyrotoxicosis. This mechanism may explain the clinical efficacy of beta-adrenergic blocking agents in the treatment of thyrotoxicosis. PMID- 2884553 TI - Dissociation of secretory responses to low-calcium and beta-adrenergic stimulation in primary hyperparathyroidism. AB - We have used a parathyroid cell perifusion system to evaluate the secretory responses to low-calcium and beta-adrenergic stimuli in series of 13 adenomatous human parathyroid tissues. In cells from all chief cell adenomas PTH secretion could be influenced by changes in extracellular calcium concentrations (either an increase in response to lower calcium concentrations or a decrease following an increase in calcium levels). However, there was marked heterogeneity in the PTH secretory response to adrenergic stimulation. In most instances, adenomatous parathyroid tissue also responded quickly and vigorously to beta-adrenergic agents (mean increase in secretion 322% +/- 52 (SEM) over baseline), although five of the 13 tissues clearly showed no PTH secretory response. Furthermore, there was a dissociation between the responses to adrenergic and low-calcium stimulation in that the presence or magnitude of the response to one type of stimulus could not be used to predict the nature of the response to the other. Studies of cells from an oxyphil adenoma revealed a very vigorous response to adrenergic stimulation (1,400% over baseline), but no response to changes in extracellular calcium concentrations. These results indicate that human parathyroid tissue is capable of a marked secretory response to adrenergic stimulation. The dissociation between secretory responses to low-calcium conditions and adrenergic agents suggests that the mechanisms of secretion by low calcium and adrenergic stimuli in adenomatous human parathyroid tissue are to some degree independent. Furthermore, aberrancies in the neoplastic parathyroid process apparently may affect either of these two secretory mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884554 TI - Beta-blockers: a new therapeutic approach to Raynaud's disease. AB - Thirty-six patients with Raynaud's disease (RD) were treated with a low dosage of beta-blockers, atenolol (50 mg/day) or propranolol (20 mg/day). Previous data have suggested that the pathophysiology of RD may be mediated by presynaptic beta adrenoceptors. In this research we report that chronic beta-blocker treatment, at low dosage, can prevent the cold-induced vasospasm. The majority of patients (28) responded to atenolol, and 8 patients refractory to atenolol responded to propranolol. PMID- 2884555 TI - Buspirone in the treatment of tardive dyskinesia. AB - Buspirone is a novel anxiolytic chemically unrelated to the benzodiazepines. In clinical trials it has been shown to be as effective as diazepam, with fewer side effects. Buspirone is primarily active in dopaminergic pathways. It has the properties of both a dopamine agonist and antagonist. In this paper a model for treatment of tardive dyskinesia with buspirone is developed, based on dopamine autoreceptor blockade. A clinical trial of buspirone in the treatment of movement disorders is warranted. PMID- 2884556 TI - A hypothesis concerning Clostridium perfringens type A enterotoxin (CPE) and sudden infant death syndrome (SIDS). AB - This study identifies the presence of Clostridium perfringens type A enterotoxin (CPE) in some gastrointestinal and serum samples from babies who had died of the Sudden Infant Death Syndrome (SIDS) and other causes. On occasion antibodies to this toxin were identified in sera. CPE is parasympathomimetic in its action. In the adult food poisoning model it is produced when the organism sporulates in vivo. This leads to speculation as to whether this toxin may play an ante-mortem role in the dying process of infants, either in the agonal stages or as a causative factor in SIDS. PMID- 2884557 TI - AIDS and mosquitoes. PMID- 2884558 TI - Esmolol--a short-acting i.v. beta-blocker. PMID- 2884559 TI - [Benzodiazepine poisoning]. PMID- 2884560 TI - T-cell neoplasms and Hodgkin's disease. PMID- 2884562 TI - Malignant lymphoma. Summation. PMID- 2884561 TI - Oncogene activation in hematopoietic malignancies. PMID- 2884563 TI - Genotoxicity of amebicide and anthelmintic drugs in Escherichia coli pol A+/pol A . AB - The amebicides dehydroemetine and chloroquine diphosphate and the anthelmintic pyrvinium pamoate, previously reported to be mutagenic in Salmonella typhimurium (Cortinas de Nava et al., 1983), were clearly shown to be genotoxic in the Escherichia coli pol A+/pol A- assay. Two other antiparasitic drugs, diiodohydroxyquin and 4-hexylresorcinol, were also found to be genotoxic in E. coli, while iodochlorhydroxyquin preferentially inhibited the pol A+ strain. From the 3 alternative testing methods employed, the liquid suspension succeeded in detecting 5 antiparasitic drugs as genotoxic; the microsuspension identified 2, and the disc diffusion method only 1. However, the metabolic activation system could only be coupled successfully and in a reproducible way to the microsuspension assay. PMID- 2884564 TI - Response of thyrotropin-secreting pituitary adenomas to a long-acting somatostatin analogue. AB - Thyrotropin-secreting pituitary adenomas are aggressive, invasive tumors that respond poorly to available surgical and medical treatments. Inappropriate release of thyrotropin by these tumors can result in hyperthyroidism. We treated five patients who had thyrotropin-secreting pituitary adenomas with the long acting somatostatin analogue SMS 201-995, which was administered by subcutaneous injection in doses of 50 to 100 micrograms every 8 to 12 hours. Serum levels of thyrotropin were dramatically reduced by treatment in four of the five patients, and levels of another tumor marker, the alpha-subunit of thyrotropin, were reduced in all five. In two patients with hyperthyroidism due to production of excess thyrotropin by the tumor, treatment with the somatostatin analogue resulted in a sustained euthyroid state. One patient who was treated for more than 16 months had a persistent reduction in serum levels of thyrotropin and iodothyronines. We conclude that SMS 201-995 is an effective means of controlling hypersecretion of thyrotropin and the associated hyperthyroidism due to thyrotropin-secreting pituitary tumors. PMID- 2884565 TI - Treatment of pituitary adenomas. PMID- 2884566 TI - Visual improvement with SMS 201-995 in a patient with a thyrotropin-secreting pituitary adenoma. PMID- 2884567 TI - Phenylketonuria. Population genetics of a disease. PMID- 2884568 TI - Evidence for neuromelanin involvement in MPTP-induced neurotoxicity. AB - Exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reproduces certain clinical, pathological, and neurochemical features of Parkinson's disease. MPTP is metabolized by monoamine oxidase Type B to 1-methyl-4 phenylpyridine (MPP+), which is selectively accumulated by high-affinity uptake mechanisms into dopaminergic neurons. Lyden et al. described low-affinity binding of MPTP to synthetic and retinal melanin. We showed that MPP+ binds to neuromelanin with high affinity, suggesting that in MPTP neurotoxicity, MPP+ enters nigral neurons by the dopamine uptake system and binds to neuromelanin, which serves as a depot, continuously releasing MPP+ until it destroys the cells. This model predicts that agents which compete with MPP+ binding to neuromelanin should partially protect the dopamine neurons from MPTP-induced toxicity. The most potent identified competitor for MPP+ binding to melanin is the antimalarial drug chloroquine, which has a high affinity for melanins. In the present study, chloroquine, administered to monkeys in conventional anti-malarial doses before MPTP, protects them from MPTP-induced parkinsonian motor abnormalities, dopamine depletion in the striatum, and neuropathological changes in the substantia nigra. PMID- 2884569 TI - No evidence for preservation of somatostatin-containing neurons after intrastriatal injections of quinolinic acid. AB - Intrastriatal injections of excitotoxic amino acids and their analogues (for example kainate and ibotenate) elicit a pattern of neuronal degeneration that is similar in many respects to that observed in Huntington's disease. In this disease there is a progressive degeneration of most types of intrinsic neuron but somatostatin and neuropeptide Y levels are increased 3-5-fold. This may be attributed to the selective preservation of a sub-class of striatal aspiny neurons, in which these two peptides are co-localized together with the enzyme NADPH-diaphorase. Beal et al. reported recently that following intrastriatal injections of quinolinic acid in rats, medium-sized aspiny neurons were selectively preserved and they suggested that quinolinic acid which is found in human brain might cause the neuronal degeneration seen in Huntington's disease. We have used immunocytochemical and enzyme histochemical techniques to examine this selective toxicity but find no evidence to support this finding. We conclude that there are substantial differences between the immunocytochemical changes detected in postmortem Huntington's disease brain and those following quinolinic acid-induced degeneration. PMID- 2884571 TI - Keeping politics out of AIDS. PMID- 2884570 TI - An amino-acid substitution involved in phenylketonuria is in linkage disequilibrium with DNA haplotype 2. AB - Phenylketonuria (PKU) is an autosomal recessive human genetic disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH, phenylalanine 4 monooxygenase, EC 1.14.16.1). PKU is a common inborn error of amino-acid metabolism in caucasian populations and approximately 1 in 50 individuals are carriers of a PKU allele. To define the molecular basis of PKU, we characterized twelve restriction fragment-length polymorphism (RFLP) haplotypes of the PAH locus in the northern European population and observed that 90% of the PKU alleles in this population are confined to four common RFLP haplotypes. We have recently reported a splicing mutation in the PAH gene that is associated with RFLP haplotype 3 which is present at about 40% of mutant alleles. We now report the molecular lesion associated with the RFLP haplotype 2 mutant allele. This defect is caused by a C-to-T transition in exon 12 resulting in an amino-acid substitution (Arg to Trp) at residue 408 of PAH. Direct hybridization analysis of the point mutation using a specific oligonucleotide probe demonstrated that this mutation is also in linkage disequilibrium with RFLP haplotype 2 alleles that make up about 20% of mutant PAH genes. PMID- 2884572 TI - [3H]ketanserin labels 5-HT2 receptors and alpha 1-adrenoceptors in human and pig brain membranes. AB - The binding characteristics of [3H]ketanserin (a reported selective radioligand for serotonin 5-HT2 receptors) and [125I]BE 2254 (which labels selectively alpha 1-adrenoceptors) were characterized in brain frontal cortex membranes of pig and man. Saturation experiments indicated that both radioligands label apparently a homogeneous class of binding sites in human and pig fontal cortex membranes. Competition experiments with [125I]BE 2254 using 17 agonists and antagonists showed monophasic and steep curves in human and pig frontal cortex membranes. The pharmacological profile of these sites is typical of alpha 1-adrenoceptors. In competition experiments with [3H]ketanserin, most of the tested compounds displayed shallow or biphasic curves. In particular, alpha 1-adrenoceptor selective antagonists (prazosin, WB 4101, BE 2254...) displaced with nanomolar affinity about 15 and 40% of the specific [3H]ketanserin binding in human and pig frontal cortex membranes, respectively. The minor component of [3H]ketanserin binding correlated highly significantly with [125I]BE 2254 binding in both membrane preparations. The major component of [3H]ketanserin binding to pig and human frontal cortex membranes correlated significantly with [3H]ketanserin binding in rat brain cortex membranes (which is essentially to 5-HT2 receptors). The present data demonstrate that [3H]ketanserin in nanomolar concentrations binds significantly to alpha 1-adrenoceptors in human and pig frontal cortex membranes; this suggests a rather limited degree of selectivity of ketanserin for 5-HT2 receptors in pig and human tissues. PMID- 2884573 TI - Inhibition of tyrosine hydroxylase in rabbit mesenteric artery and vas deferens by catechol oestrogens. AB - In the present study we have investigated the effects of oestrogens, catechol oestrogens, and catecholamines on tyrosine hydroxylase (TH) activity derived from rabbit mesenteric artery and vas deferens. Both catechol oestrogens, 2 hydroxyoestradiol (2OHE2) and 2-hydroxyoesterone (2OHE1), inhibited TH activity in mesenteric artery and vas deferens in a concentration-dependent manner with potencies that were higher than those for noradrenaline but lower than that for dopamine. When added to the reaction medium along with increasing concentrations of a pterin cofactor (200 to 1,500 mumol/l DMPH4), the catechol oestrogens (200 mumol/l) increased the apparent Km for DMPH4 without altering the maximum velocity (Vmax) of the reaction. Similar results were obtained with the addition of noradrenaline (200 mumol/l) and dopamine (120 mu/mol). Apparent Ki values obtained for the catecholamines and catechol oestrogens were within the same order of magnitude and varied from 30 mumol/l for dopamine and 2OHE2 to 183 mumol/l for 2OHE1. Oestradiol (E2) and 2-methoxyoestradiol (2MeOE2), i.e., oestrogens that do not possess a catechol moiety, exhibited only weak inhibitory effects on TH activity. At the highest concentration tested (1 mmol/l), they did not reduce enzyme activity below 58% of control values. Kinetic analysis revealed that these two oestrogens did not consistently affect either the Vmax of hydroxylation or the Km for DMPH4. It is concluded that catechol oestrogens inhibit TH activity with a potency comparable to noradrenaline and dopamine. This inhibition is by competition with the pterin cofactor. Oestrogens that to not possess a catechol moiety are not effective inhibitors of TH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884574 TI - The effects of some alpha-adrenoceptor antagonists on the responses of the canine saphenous vein to B-HT 933, UK-14304 and methoxamine. AB - The benzoquinolizines Wy 25309, Wy 26703 and Wy 27127, previously reported as potent antagonists at presynaptic alpha 2-adrenoceptors were also potent antagonists of B-HT 933 in isolated saphenous veins of the dog confirming their activity at post synaptic alpha 2-adrenoceptors. Yohimbine was a more potent antagonist of B-HT 933 in isolated saphenous vein than were the Wy compounds or idazoxan contrasting with the reported potencies of these compounds at presynaptic sites in rat vas deferens and raising the possibility of differences between pre- and postsynaptic alpha 2-adrenoceptors. Contractions of the saphenous vein were observed with high concentrations of idazoxan. PMID- 2884575 TI - Studies on alpha adrenoceptors in guinea-pig peripheral lung strips. AB - Contractile responses of guinea-pig peripheral lung strips to noradrenaline were determined in the presence of propranolol (2.5 X 10(-6) mol/l). All strips (n = 44) contracted to noradrenaline and a geometric mean EC50 of 1.4 X 10(-6) mol/l (1.1 X 10(-6) mol/l, 1.8 X 10(-6) mol/l 95% confidence limits) was obtained. Contractions were antagonised by phentolamine (5 X 10(-7)-10(-5) mol/l) and by prazosin (10(-8)-10(-7) mol/l). Dose-ratios (DR) were calculated and log (DR-1) was plotted against log concentration of antagonist to yield slopes (+/- SE) of 0.84 +/- 0.14 and 0.73 +/- 0.22 respectively which were not significantly different from unity. A pA2 value (+/- SE) of 6.7 +/- 0.2 was obtained for phentolamine and 7.5 +/- 0.1 for prazosin. Yohimbine (10(-7)-10(-5) mol/l) did not significantly affect the maximal tension generated or the EC50 values for noradrenaline. These results suggest that alpha 1 adrenoceptors are mediating the contractile responses to noradrenaline. In the presence of cocaine (10(-5) mol/l, n = 18), normetanephrine (2 X 10(-5) mol/l, n = 15), hydrocortisone (2.5 X 10(-5) mol/l, n = 15) and normetanephrine (2 X 10(-5) mol/l) plus cocaine (10(-5) mol/l, n = 15) pA2 values for phentolamine of 6.9, 6.7, 6.6, and 6.3 respectively were obtained. Since these pA2 values are not significantly different from 6.7, it is unlikely that this original pA2 value, which is lower than values obtained with phentolamine at alpha-adrenoceptors in other tissues, may be explained by neuronal or extraneuronal uptake of noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884578 TI - Physician assistants in North Carolina, 1986. A report of a survey sponsored by the North Carolina Academy of Physician Assistants. PMID- 2884576 TI - Cardiovascular effects in rats of alpha 1 and alpha 2 adrenergic agents injected into the nucleus tractus solitarii. AB - The cardiovascular effects of selective alpha 1 and alpha 2 agonists and antagonists injected into the nucleus tractus solitarii (NTS) were studied in urethane-anesthetized rats. Methoxamine (0.3-3 micrograms) injected bilaterally into the NTS caused a dose-dependent increase in blood pressure and heart rate. Phenylephrine (6 micrograms) and an imidazolidine derivative St 587 (3 micrograms) similarly injected also produced an increase in blood pressure, whereas alpha-methylnoradrenaline and an azepine derivative B-HT 920 (1 and 3 micrograms) caused a decrease in blood pressure and heart rate. The pressor response to methoxamine (1 microgram) was markedly inhibited by prazosin (0.3 microgram) injected into the same sites or hexamethionum (25 mg/kg, i.v.). Prazosin (0.3 microgram) alone injected bilaterally into the NTS did not affect the blood pressure, while yohimbine (0.1 microgram) similarly injected increased the pressure. These results suggest that in the rat NTS there exist alpha 1 adrenoceptors responsible for an increase in arterial pressure. The NTS alpha 2 adrenoceptors seem to be involved in the tonic regulation of arterial pressure. PMID- 2884579 TI - [Epidemiology of AIDS and HIV infections in the Netherlands; current status and prognosis for 1987-1990]. PMID- 2884577 TI - Involvement of opioid receptors in phencyclidine-induced enhancement of brain histamine turnover in mice. AB - When the histamine (HA) turnover in the brain of mice was estimated on the basis of the pargyline-induced accumulation of tele-methylhistamine (t-MH), a predominant metabolite of brain HA, the enhancing effect of phencyclidine (PCP) on the HA turnover was antagonized by a large dose of naloxone. However, a dopamine receptor antagonist haloperidol, which is also a potent sigma receptor antagonist, did not inhibit the effect of PCP on the HA turnover. [D-Ala2,D Leu5]enkephalin, a prototypic delta opioid agonist, markedly enhanced the HA turnover. The effect of this peptide was demonstrated not only when the HA turnover was determined by the pargyline-induced t-MH accumulation but when it was estimated by the HA depletion induced by alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase. A sigma agonist, SKF-10047, and a kappa agonist, ethylketazocine, had no PCP-like enhancing effect on the HA turnover. These results suggest that PCP enhances the brain HA turnover in mice by stimulating, probably indirectly, endogenous opioid systems. PMID- 2884580 TI - [Postoperative abscesses and empyemas. Apropos of 13 cases]. AB - 13 cases of severe intracranial postoperative infections, abscesses and/or empyema, are reported. These lesions, whose clinical diagnosis is often difficult, have benefited from C.T. scan. The diffusion of the infectious process in operatory focus, the frequency of Staphylococcal origin and the importance of high doses antibiotherapy must be underlined. This one is, of course, an indispensable complement to reintervention, but it may be utilized alone with success in selected cases, or insure the definitive cure when reintervention is partial. PMID- 2884581 TI - [Amino acids in human epileptogenic foci]. AB - The functional status of GABA synapses together with tissue levels of other putative neurotransmitter amino acids was studied in epileptogenic foci (identified by stereo-EEG) removed neurosurgically from 14 epileptic patients unresponsive to anti-epileptic medication. L. glutamic acid decarboxylase was lower than normal in epileptogenic cortical tissue from 10 to 12 patients. 3H GABA-"A" receptor binding was low in all epileptogenic tissue examined. GABA levels were unchanged, whereas glutamate was increased in 7 patients. These studies confirm previous observations that there is a decreased functional activity of GABA synapses in a high proportion of epileptogenic foci. Therefore these data indicate that there is indeed an imbalance between excitatory and inhibitory neurotransmitter systems. PMID- 2884582 TI - [Physiological and physiopathological aspects of the atrial natriuretic factor]. AB - The discovery of the atrial natriuretic factor (ANF) has opened a new field in modern biology. After rapid isolation and identification of this new peptide from atrial granules, it is now evident that this new hormone has a wide variety of actions with general implication in the control of vascular tone, sodium and water balance, hormonal secretion as well as neuronal functions. The major mode of action of this hormone is transmitted via its interaction with a membrane enzyme, particulate guanylate cyclase, leading to increases of cGMP levels. This nucleotide is a faithful marker of ANF action correlating with all functions ascribed to ANF up to date. Significant increases of ANF as well as of cGMP have been discovered in heart and renal failure, secondary hypertension and other states with altered salt-water balance, impairment of heart function and particularly increase of atrial pressure. The increases of levels and relative inefficiency of increased ANF have to be carefully interpreted in face of increased levels of cGMP. It can be expected that new pharmacological developments will occur in this area issuing from both our increasing knowledge concerning the peripheral mode of action of this hormone, its physiological implications as well as its pharmacological effectiveness in diseases with altered salt-water balance, cardiac function and blood pressure disregulation. PMID- 2884583 TI - Selective alteration of mouse brain neurotransmitter release with age. AB - The release of acetylcholine (ACh), glutamate (GLU) and dopamine (DA) from various brain regions was investigated in young (3 month) and old (30 month) Balb/c mice. Aging increased the basal release of GLU (77%) and DA (29%) in striatum and GLU in hippocampus (94%); the concentrations of these neurotransmitters in the media after K+ stimulation were unaltered by aging. Although the basal release of ACh was not altered by age, K+-stimulated ACh release was reduced in striatum. The age-related increases in basal GLU and DA release may be important in the pathophysiology of cell death during aging. PMID- 2884584 TI - Detoxification enzymes following intrastriatal kainic acid. AB - A complete explanation of the neurotoxicity that follows kainic acid (KA) injection into the rat striatum is lacking. An assessment of the chronological course after intrastriatal KA injection of the activities of enzymes preferentially concentrated in glia or involved in the detoxification of oxygen metabolites is accomplished. An enhancement of the specific activities of glutathione peroxidase (GP) and catalase is found without an alteration in the specific activity of superoxide dismutase (SOD). There is no increase in the in vivo striatal levels of malondialdehyde, a putative indicator of lipid peroxidation, the expected result of cell membrane damage from oxygen metabolites. Understanding the mechanism and importance of the preferential induction of the activities of the detoxification enzymes will require further study. PMID- 2884585 TI - Beta-endorphin and dynorphin participate in the stress-induced release of prolactin in the rat. AB - In the rat, exposure to stress increases prolactin (Prl) secretion, and endogenous opioid peptides (EOP) are believed to play a role in this response. The aim of the present study was to evaluate the specific involvement of the different EOP (i.e. beta-endorphin [beta-END], dynorphin A [DYN-A], methionine enkephalin [Met-ENK], and/or opiate receptors (i.e., mu/epsilon, kappa, delta) in the stress-related increase in circulating Prl. Rats were subjected to inescapable intermittent footshock (60 Hz, 2.5 mA, 1 s duration, 2 h) 2 h after the intracerebroventricular (i.c.v.) injection of specific antisera raised against beta-END, DYN-A or Met-ENK. In addition, selective opiate antagonists (beta h-END-[6-31], a peptide beta-END antagonist [5 nmol, i.c.v.], beta funaltrexamine [beta-FNA], an mu 1 receptor antagonist [4.8 nmol, i.c.v.], Mr 1,452 MS and Mr 2,266 BS, two kappa-receptor antagonists [10 mg/kg body weight, i.p.], ICI 154, 129, a delta-receptor antagonist [100 nmol, i.c.v.]) were administered prior to footshock stress. Blood samples were collected through an indwelling jugular cannula. Exposure to footshock rapidly and significantly increased plasma Prl levels. This stress-induced release of Prl was reduced by both antisera against beta-END or DYN-A, as well as by pretreatment with beta h END-(6-31), beta-FNA and kappa-receptor antagonists. Antiserum against Met-ENK and delta-antagonist were inactive. These results suggest that the activation of the two endogenous opioid systems, beta-END and DYN-A, centrally modulate the release of Prl induced by footshock stress. PMID- 2884586 TI - Modulation of neuronal activity in the hippocampus by 5-hydroxytryptamine and 5 hydroxytryptamine1A selective drugs. AB - The interactions between 5-hydroxytryptamine (5-HT), 8-hydroxy-2-(N,N dipropylamino)-tetralin (8-OH-DPAT), buspirone, 2-(4-(4-(2-pyrimidinyl)-1 piperazinyl)butyl)-1,2-benzisothiazol-3- (2H)one-1, 1-dioxide-hydrochloride (TVX Q 7821) and ketanserin, and putative 5-HT receptors were analyzed using both radioligand techniques and an in vitro hippocampal slice preparation. The potencies of the drugs were determined at 5-HT1A binding sites labelled by [3H]8 OH-DPAT in hippocampal membranes from the rat. The binding site had similar affinity for 5-HT, 8-OH-DPAT, buspirone and TVX Q 7821, whereas ketanserin was essentially inactive. Physiological effects of these drugs were also examined using an in vitro hippocampal slice preparation. With the exception of ketanserin, application of each drug to the bath modulated the amplitude of the field potential recorded in the pyramidal layer of CA1 evoked by stimulation of Schaffer collaterals. Application of micromolar concentrations of 5-HT produced an initial increase in the population spike followed by a return to near baseline levels within 5 min. By contrast, the amplitude of the population spike was reduced in a dose-dependent manner by micromolar concentrations of 8-OH-DPAT, buspirone and TVX Q 7821, beginning 5 min after application of drug. Ketanserin did not affect the amplitude of the population spike and it did not antagonize the effects of 5-HT, buspirone or TVX Q 7821. Neither buspirone nor 8-OH-DPAT altered the initial increase in population spike induced by 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884587 TI - Inhibition by phencyclidine of excitatory amino acid-stimulated release of neurotransmitter in the nucleus accumbens. AB - The effects of phencyclidine (PCP) on the release of acetylcholine and dopamine, stimulated by excitatory amino acid agonists was examined in slices of nucleus accumbens of the rat. In slices incubated in [3H]choline or [3H]dopamine, the amount of tritium efflux produced by 1 mM N-methyl-D-aspartate (NMDA), kainic acid (KA) or quisqualic acid (QA) was compared with that produced in the presence of varying concentrations of phencyclidine. N-Methyl-D-aspartate stimulated the calcium-dependent release of both ACh and DA, which was completely inhibited by physiological concentrations of magnesium and inhibited by 2 aminophosphonovalerate (2-APV). Kainic acid- and quisqualic acid-stimulated release of ACh and DA was partially inhibited by magnesium or by 2-APV. Phencyclidine inhibited NMDA-stimulated release of ACh and DA with IC50's around 100 nM. Phencyclidine (0.1 microM) also significantly inhibited kainic acid and quisqualic acid-induced release of ACh in magnesium-free but not magnesium containing buffer, suggesting that the effect of PCP on kainic acid- and possibly quisqualic acid-stimulated release of ACh is on that part of the response which is mediated by NMDA receptors. The results suggest that the inhibition by PCP of the release of ACh and DA in the nucleus accumbens is selective for NMDA-type receptors. PMID- 2884588 TI - Comparison of the acute actions of amine-depleting drugs and dopamine receptor antagonists on dopamine function in the brain in rats. AB - The effects of the monoamine depleting drugs oxypertine, tetrabenazine and reserpine were compared with those of the dopamine receptor antagonists, chlorpromazine and trifluoperazine, on behavioural and biochemical indices of dopamine function in the brain. Oxypertine (0.625-20 mg/kg, i.p.), chlorpromazine (0.625-20 mg/kg i.p.) and trifluoperazine (0.0625-2.0 mg/kg i.p.), administered to rats 1 hr previously, inhibited stereotyped behaviour induced by both amphetamine (5.0 mg/kg i.p.) and apomorphine (1.0 mg/kg, s.c.) in a dose dependent manner. Tetrabenazine (0.625-20 mg/kg i.p., 1 hr previously) inhibited stereotypy induced by amphetamine but not that induced by apomorphine. Reserpine (0.1 10 mg/kg i.p., 6 hr previously) did not inhibit, but in larger doses, tended to enhance the stereotyped responses to both amphetamine and apomorphine. Oxypertine (10 mg/kg, i.p., 1 hr previously), tetrabenazine (5 mg/kg i.p., 1 hr previously) and reserpine (2.5 mg/kg i.p., 6 hr previously) reduced the content of dopamine in the striatum but increased the concentrations of homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC). Chlorpromazine (5 mg/kg i.p.) and trifluoperazine (0.5 mg/kg i.p.), given 1 hr previously, did not alter concentrations of dopamine in the striatum but increased those of HVA and DOPAC. Oxypertine, chlorpromazine and trifluoperazine weakly inhibited dopamine stimulated adenylate cyclase in homogenates of the striatum in the rat. Tetrabenazine and reserpine had no effect. Similarly, trifluoperazine and chlorpromazine displaced the specific binding of [3H]piflutixol to membranes from the striatum. Oxypertine also was weakly effective, but tetrabenazine and reserpine were without effect. Trifluoperazine, chlorpromazine and oxypertine displaced specific binding of [3H]spiperone and [3H]N,n-propylnorapomorphine (NPA) to preparations of the striatum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884589 TI - Characteristics of chloride-dependent incorporation of glutamate into brain membranes argue against a receptor binding site. AB - Although membrane sites from brain, labelled with [3H]glutamate (Glu) under sodium-free conditions, are thought to represent excitatory receptors, certain anomalous characteristics of the kinetics of apparent binding raised the question of whether transport might contribute to this process, prompting a closer examination of it. Hyperosmolar media and low incubation temperatures (4 degrees C) both led to decreases in the apparent specific binding of [3H]glutamate to membranes from the brain of the rat in the presence of chloride. Furthermore, only 15% of the [3H]glutamate, bound at 37 degrees C, was dissociable when the membranes were then cooled to 4 degrees C. The binding of [3H]glutamate was increased in the presence of certain dipeptides such as L-phenylalanyl-L glutamate (Phe-Glu); and the binding augmented by the presence of Phe-Glu, was also sensitive to temperature and osmolarity of the incubation buffer. Sonication of membranes in 5 mM glutamate increased the apparent binding of [3H]glutamate and abolished the stimulatory effect of Phe-Glu. These findings are consistent with the hypothesis that chloride-dependent association of [3H]glutamate with membranes from brain reflects, in part, a sequestration process, which may be driven by glutamate exchange. PMID- 2884590 TI - Behavioural and biochemical evidence for the release of noradrenaline in mouse brain by TRH and some of its biologically stable analogues. AB - Small doses of clonidine probably induce hypoactivity (a distinct form of sedation) by stimulating presynaptic alpha 2-adrenoceptors. This was attenuated by injection of 0.1-10 mg/kg of thyrotropin releasing hormone (TRH) or its biologically stable analogues, CG3509, CG3703 and RX77368, when these were given 10 min before clonidine. This effect was dose-dependent in all cases, but the analogues were more potent than TRH. The TRH metabolites, TRH acid and histidyl proline diketopiperazine (10 mg/kg) were without effect. This response was still attenuated by the analogues, but not TRH, when these were given 1 hr before clonidine. The results, therefore, suggested that it was the basic tripeptide structure which was active and TRH was less potent than its analogues because of rapid metabolism. Attenuation of hypoactivity by TRH and analogues was not due to increased dopaminergic function because apomorphine (5 mg/kg) was ineffective. Thyrotropin releasing hormone (20 mg/kg), CG3509 (10 mg/kg) and CG3703 (1 mg/kg) also induced locomotor activity and produced various other behavioural changes. This was inhibited by prazosin (3 mg/kg) and haloperidol (0.5 mg/kg) but not by yohimbine (1 mg/kg). Apomorphine (5 mg/kg)-induced activity was inhibited by haloperidol and yohimbine but not by prazosin. This indicated that the activity produced by the TRH compounds, but not apomorphine, was partly mediated by alpha 1-adrenoceptors. Both CG3509 (10(-5) and 10(-4) M) and RX77368 (10(-4) M) evoked the release of endogenous noradrenaline from slices of hypothalamus in vitro. The TRH analogues, however, had no affinity for alpha 1- or alpha 2-adrenoceptors in ligand-receptor binding experiments. Viewed overall, the data showed that TRH and its analogues induced the release of noradrenaline in the brain. In addition, a comparison of the behavioural effects of TRH compounds with dopamine and alpha 1 adrenoceptor agonists suggested that in mice these behavioural responses resulted from stimulation of both noradrenergic and dopaminergic function. PMID- 2884591 TI - Effects of bifemelane hydrochloride on cortical neuronal activity in cats. AB - The effects of bifemelane hydrochloride on neuronal activity in the visual cortex of the cat were studied by microiontophoretic application under methoxyflurane anesthesia. Of 195 neurons examined with both acetylcholine (ACh) and bifemelane, 67 cells (34%) were excited and 7 cells (4%) were inhibited by ACh. The effect of bifemelane was excitatory on 122 neurons (63%), inhibitory on 20 (10%) and unchanged on the rest. In 60 cells out of the above 122 neurons, bifemelane showed a similar discharge pattern to ACh with a slow onset and delayed termination. The bifemelane-induced excitation was, in 18 out of 22 cells, antagonized by atropine (30-40 nA). Also, a potentiation in bifemelane-induced discharges by physostigmine (30-50 nA) was observed in 14 of the 32 cells tested. The firing evoked by ACh (80-100 nA) was potentiated during of after the application of bifemelane (30-40 nA) in 9 out of 29 neurons, which were not excited by bifemelane alone. These results suggest that neuronal discharges produced by bifemelane are induced at least in part, through a muscarinic ACh receptor, although other mechanisms may possibly be involved. PMID- 2884592 TI - Hypnotics: clinical value of pharmaco-EEG methods. AB - The central effects of sedative-hypnotic drugs were defined through the use of electroencephalographic (EEG) techniques in two species (rat and cat). In immobilized rats, spectral and visual electrocorticogram analysis provides a means of studying and comparing different profiles of sedative-hypnotic drugs. As with spectral analysis, Hjorth's descriptors allow one to detect the sedative effects of drugs and to study drug interactions in acute preparations. We have evaluated the action of hypnotics on the sleep-wakefulness cycle in freely implanted rats during their maximally active period because it is easier to estimate the duration of the sedative effect. We have also examined the action of sedative-hypnotic agents in rats and cats because of the different species reactivity to drugs such as benzodiazepines. These EEG methods are of value in the development of new hypnotic agents. PMID- 2884593 TI - Piracetam interactions with neuroleptics in psychopharmacological tests. AB - Two psychopharmacological tests which usually predict neuroleptic activity were conducted after joint administration of piracetam and three neuroleptics (haloperidol, fluphenazine and sulpiride) chosen for their different chemical classes and dopaminergic affinities. In these tests, specific doses of the neuroleptics were used to determine whether piracetam induced potentiation or antagonism of their action. Overall, piracetam increased neuroleptic action regardless of the administration timetable used, but the interaction of fluphenazine differed from that of the other two substances, because piracetam did not modify its action in a specific test of the presynaptic DA-2 dopaminergic receptors. This variation for fluphenazine may be explained by the fact that its pKa value is closer to that of piracetam, thus preventing better bioavailability of the neuroleptic, or its better affinity for DA-1 dopaminergic receptors. Nevertheless, the variation may have been due to a differing affinity for dopaminergic receptors, although this hypothesis is not completely satisfactory because it does not account for differences due to the administration timetable. It is thus suggested that action occurs on nonspecific sites and has the effect of increasing overall neuroleptic bioavailability. PMID- 2884594 TI - CSF somatostatin in multiple sclerosis: reversible loss of diurnal oscillation in relapses. AB - CSF and venous blood were sampled hourly during 24 hours in 6 control subjects and in 12 patients with MS, 5 of whom were in stable phase and 7 in relapse. CSF somatostatin immunoreactivity was 166 +/- 5.3 (SFM) pg/ml in controls at noon and rose around midnight to 208 +/- 3.8 pg/ml, then decreased to basal levels at about 5 hours and exhibited another small peak 3 hours later. Almost identical patterns were found in patients with MS during stable phase. During relapse, CSF somatostatin was reduced to 99 +/- 9.2 pg/ml and showed no variation from this value. CSF albumin was similar in the three groups and exhibited no fluctuations. Diurnal patterns of serum growth hormone were similar and unrelated to the oscillations in CSF somatostatin, indicating that hypothalamic release was insignificant in the overall production and in variations. The observation that the CNS releases somatostatin at lower levels during relapse in MS and that these do not oscillate may suggest that the constant low contents represent passive spillover from somatostatin-containing neurons, while the undulating levels above them are representative of active, yet unknown neurophysiologic (eg, neurotransmitter) functions which become reversibly extinct in relapse. PMID- 2884595 TI - Treatment of lethal pertussis vaccine reaction with histamine H1 antagonists. AB - We studied mortality after pertussis immunization in the mouse. Without treatment, 73 of 92 animals (80%) died after injection of bovine serum albumin (BSA) on day +7 of pertussis immunization. After pretreatment with 3 mg of cyproheptadine, 2 mg mianserin, or 2 mg chlorpheniramine, only 5 of 105 animals (5%) died after receiving BSA on day +7 (p less than 0.001). Blockade of histamine H1 receptors may reduce mortality in pertussis immunization-induced encephalopathy in mice. PMID- 2884596 TI - [Hyperthermia and properties of isolated nerve endings in the cerebral cortex of rabbits]. PMID- 2884597 TI - The free cutaneous scapular flap in lower extremity reconstruction. PMID- 2884599 TI - [The course of gastric ulcer. Results 3 years after the diagnosis]. PMID- 2884598 TI - [Effects of terfenadine on esophageal motility in man]. PMID- 2884600 TI - [Treatment of functional disorders of the digestive system with combination therapy]. PMID- 2884601 TI - Use of laparoscopy for the localization of impalpable testes. AB - Laparoscopy is a simple, safe and sure diagnostic method in order to visualize an abdominal testis. When there is no abdominal testis at laparoscopy, the vas deferens and the testicular vessels have to be looked for very carefully. When both these structures pass through the internal inguinal ring, operation can be limited to the inguinal region. The results of laparoscopy are reported in nine patients with impalpable testis. PMID- 2884602 TI - Somatostatinergic projections from the amygdala to the bed nucleus of the stria terminalis and medial preoptic-hypothalamic region. AB - Somatostatinergic projections of the amygdala to the bed nucleus of the stria terminalis (BST) and medial preoptic-hypothalamic region were examined using a technique that combines retrograde axonal transport with peroxidase antiperoxidase immunohistochemistry. With injections of wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) into either the BST or medial preoptic-hypothalamic region numerous double-labeled cells exhibiting both retrograde labeling and somatostatin-like immunoreactivity were observed in the medial amygdaloid nucleus and intra-amygdaloid portion of the BST. Additional cells were seen in the central nucleus, basomedial nucleus and anterior amygdaloid area. Although WGA-HRP labeled neurons and somatostatin-positive cells were observed in the lateral and basolateral amygdaloid nuclei, few double labeled neurons were found. PMID- 2884603 TI - Differential effect of intraterminal sodium on spontaneous quantal release of transmitter in two neuromuscular junctions of crayfish. AB - Nerve terminals on the superficial abdominal extensor muscle and the claw opener muscle of small crayfish were loaded with sodium by bath application of 100 mumol/l veratridine in superfusates where normal Ca2+ was removed (low-Ca2+ superfusate). In both preparations this caused an increase in spontaneous quantal release of excitatory and inhibitory transmitter which was evaluated by means of the noise analysis technique. About 2.5 min after application of veratridine, when spontaneous quantal release had largely ceased, the normal Ca2+ concentration was reestablished. This increased transiently the quantal release rate a second time. However, release activated by Ca2+ application was much more vigorous at the superficial abdominal extensor muscle than at the claw opener. At the superficial abdominal extensor muscle on average about 8% of the total number of quanta could be released in low Ca2+ and 92% in normal Ca2+ superfusate, while at the claw opener 75% of the quanta were released in low Ca2+ and 25% in normal Ca2+ superfusate. The experiments suggest that intraterminal sodium has a differential effect in the terminals of the two preparations. Possibly, the intraterminal source from which Na+ may liberate Ca2+ is more restricted in the superficial abdominal extensor muscle than in the opener muscle of the claw. PMID- 2884604 TI - Purified opioid mu-receptor is of a different molecular size than delta- and kappa-receptors. AB - Opioid mu-receptors were solubilized from rat brains with 0.5% Triton X-100 in the presence of 0.32 M sucrose and then purified with 6-succinyl morphine-Affi Gel 102 column. Purified materials showed a major band with mol.wt. 58,000 Da and a minor band with mol.wt. 41,000 Da. Affinity cross linking with [3H]DAGO, a selective mu-opioid agonist, to the neural membranes and purified materials revealed that opioid mu-binding protein has a mol.wt. of 58,000 Da, a value totally different from that of delta- (mol.wt. 18,500 Da) and kappa- (mol.wt. 36,000 Da) binding protein. PMID- 2884605 TI - Opiates inhibit the discharges of fine afferent units from inflamed knee joint of the cat. AB - The spontaneous discharges in 15 out of 19 small-diameter afferent units from inflamed knee joints of anaesthetized cats were significantly inhibited by one or several opiates (morphine in the dose range 1.0-5.0 mg/kg; gly-ol 0.5-5.0 mg/kg; U50488 1.0-10.0 mg/kg; ethylketocyclazacine 0.5-4.0 mg/kg administered by close arterial injection into the joint). In the majority of cases a subsequent injection of naloxone (1 mg/kg i.a.) significantly reversed this effect. These data provide an electrophysiological demonstration that opiates may act on opiate receptors located at peripheral sites of primary afferent fibres and hence exert a peripheral 'analgesic' effect. PMID- 2884606 TI - Neurotensin-containing neurons in the canine enteric innervation. AB - The intrinsic innervation of the gastrointestinal tract has been demonstrated to contain numerous peptidergic neurons. Neurotensin, originally isolated from bovine hypothalamus, has been localized in intestinal epithelial endocrine cells but not convincingly in the enteric innervation. The present study demonstrates the presence of neurotensin-immunoreactive neurons and nerve fibers in the canine submucous and myenteric ganglia. The peptide was characterized as neurotensin 1 13 by high pressure liquid chromatography and there was a mean concentration of 18.4 +/- 3.9 pmol (+/- S.E.M., n = 3) per g wet weight of submucosal extract. These neurons were a separate population from the vasoactive intestinal peptide- and somatostatin-immunoreactive cell bodies. These results demonstrate that neurotensin is present in significant amounts in the canine submucous plexus. PMID- 2884607 TI - Distribution of phenylethanolamine-N-methyltransferase (PNMT)-immunoreactive neurons in the avian brain. AB - The distribution of neurons immunoreactive to tyrosine hydroxylase and phenylethanolamine-N-methyltransferase (PNMT) were described in adjacent sections of the avian medulla oblongata. PNMT-positive neurons were found in two bilaterally symmetrical columns in the ventrolateral and dorsomedial medulla. Within the ventrolateral column, PNMT cells were centered in and around the lateral paragigantocellular and lateral reticular nuclei. In the dorsomedial medulla, PNMT neurons were concentrated within and around the nucleus of the tractus solitarius. The distribution of PNMT-immunoreactive neurons in the avian medulla is similar to those observed in mammals, except there appears to be a greater number of PNMT-positive cells in the bird. PMID- 2884608 TI - Bursting in human epileptogenic neocortex is depressed by an N-methyl-D-aspartate antagonist. AB - Intracellular recordings were performed in human neocortical neurons in 'in vitro' slices of brain samples excised during surgical treatment of epilepsy. In 14 of 38 neurons obtained from cortex exhibiting interictal spiking, bursts of action potentials arising from a synaptic depolarizing potential could be elicited by extracellular focal stimulation of adequate strength. The N-methyl-D aspartate (NMDA) antagonist 2-amino-5-phosphonovalerate (APV) was capable of reducing and eventually blocking these bursts without affecting the repetitive firing evoked by depolarizing intracellular pulses or the membrane input resistance. These data suggest a role played by NMDA receptors in the bursting activity displayed by human neurons from spiking cortical areas and demonstrate a potential use of NMDA antagonists as antiepileptic drugs. PMID- 2884609 TI - Glial and potassium responses to an afferent volley: suppression by enkephalin in the rat spinal cord in vitro. AB - A transient rise in the extracellular potassium concentration following activation of internuncial neurons by an afferent volley was recorded intracellularly from glial cells and by K+-sensitive electrodes in the superficial dorsal horn of the rat spinal cord in vitro. Methionine (Met) enkephalin did not affect the extracellular potassium level at rest but suppressed the potassium response elicited by afferent volleys. This effect was abolished by naloxone. In the chronically deafferent spinal cord combined with the block of synaptic transmission by Mg2+, Met-enkephalin suppressed the transient rise of the extracellular potassium concentration induced by L glutamate. It is concluded that synaptic excitation of interneurons in the superficial dorsal horn is suppressed by the postsynaptic action of Met enkephalin. PMID- 2884610 TI - 2-Amino-5-phosphonovalerate attenuates the severe hypoglycemia-induced loss of perforant path-evoked field potentials in the rat hippocampus. AB - The effects of severe hypoglycemia on perforant path-evoked field potentials were examined in the rat hippocampus. Although a complete loss of this response was noted when blood glucose concentration fell below 1 mM, this occurred before cessation of electroencephalogram (EEG) activity. Both spontaneous and evoked responses recovered partially following glucose readministration. D-2-Amino-5 phosphonovalerate, an NMDA-sensitive acidic amino acid receptor antagonist, facilitated this recovery from the hypoglycemic challenge when administered via a dialysis probe. PMID- 2884611 TI - Purification of the alpha toxin of Clostridium perfringens type A by ultrafiltration and gel chromatography. AB - Clostridium perfringens type A toxin produced in Jayko & Lichstein medium was subjected to various concentration and purification procedures. The results obtained with 3 different ultrafiltration membranes followed by gel filtration showed that by using Millipore PSED OHV10 and Amicon XM-100 filter membranes in combination, a three-hundred-and-fivefold purification could be achieved as against a twelvefold increase obtained with ammonium sulphate/acetone precipitation. The lecitovitelin test was more sensitive than the haemolytic activity in determining the alpha toxin activity. The optical density, measured at 280 nm, did not reveal any alpha toxin activity in the relevant toxic fractions. PMID- 2884612 TI - Further studies of the clinical pathology of sweating sickness in cattle. AB - Experimentally-induced cases of sweating sickness in calves were used in an effort to correlate the blood chemistry with some of the known pathological changes. Results showed that the "sweating" associated with necrotic dermatitis did not alter blood electrolyte levels. Laboratory evidence of a disseminated intravascular coagulopathy was found which correlated with the microthrombi described in cases of sweating sickness. A high blood cortisol level was found in one of the animals that died from the disease and could possibly be used as a prognostic indicator in clinical cases. Recommendations are made with regard to the supportive treatment based on the clinical pathological findings. PMID- 2884613 TI - Ovine hepatogenous photosensitivity caused by the plant Nidorella foetida (Thunb.) DC. (Asteraceae). AB - Following a field outbreak of hepatogenous photosensitivity in sheep, an identical condition was reproduced experimentally by dosing 2 sheep with green, homogenized, Nidorella foetida material, collected from the camp where the outbreak occurred. This is a rare, unpalatable, aromatic shrub found in swampy places in the south-western Cape Province. The main lesion was a hepatosis, characterized by peripheral coagulative necrosis and midzonal degeneration in the 2 acute cases and mild bile duct proliferation and hepatic regeneration in the more chronic field case. Botanical, toxicological, clinical and pathological data are given. PMID- 2884614 TI - [Polyarteritis nodosa based on a case report]. PMID- 2884615 TI - Organization educates medical assistants. PMID- 2884616 TI - [Diagnostic value of 4 biological markers: lactate dehydrogenase, phosphoglucoisomerase, carcinoembryonic antigen and gammaglutamyl transpeptidase, systematically determined in patients in a hematology-oncology department]. AB - This article is concerned with a prospective study about the systematical, simultaneous and comparative assay of four biological markers (carcino-embryonic antigen, lactate dehydrogenase, gammaglutamyl transferase and phosphohexose isomerase). This study was conducted in a department of Hematology and oncology on 258 patients. The dosage of each marker separately does not appear to be of diagnostical interest because of a lack of sensibility and specificity. But when there is a positive statistical correlation between several makers, their simultaneous dosage may allow the diagnostic of cancer and sometimes the determination of its origin. PMID- 2884617 TI - [Viral etiology of T-cell leukemia and AIDS]. PMID- 2884618 TI - Cryptorchidism: a pediatrician's view. AB - Cryptorchidism is one of the most common congenital anomalies afflicting male children. This article reviews some of the existing literature regarding this condition for the purpose of presenting the pediatrician with a synopsis of possible diagnosis and treatment options. PMID- 2884619 TI - Correlation between monoamine content and other parameters of cerebrospinal fluid in aneurysmal subarachnoid haemorrhage: a case report. AB - The monoamine content and other parameters of cerebrospinal fluid (CSF) were studied in aneurysmal subarachnoid haemorrhage (ASH). The blood content of CSF was determined by the protein concentration and cell count, while the haemostatic status of the patient was characterized by the prothrombin level of blood. The serotonin content of CSF was elevated at the beginning of ASH (high protein content and fresh blood cells in CSF, and low level of prothrombin in blood). Later the level of serotonin and protein of CSF decreased, while the prothrombin level of blood increased. During rebleeding on the 20th day after admission, the CSF serotonin and protein content increased again, while the prothrombin level of blood was decreased. The dopamine and noradrenaline levels of CSF markedly decreased on the 11th day after ASH, but in the following days these parameters returned to the control level. The findings suggested that the serotonin content of CSF originated mainly from extravasated blood. The decreased level of dopamine and noradrenaline 11 days after ASH might be connected with increased blood viscosity, decreased peripheral blood pressure or other changes. PMID- 2884620 TI - [Profile of the adverse effects of neuroleptic drugs in relation to its receptor binding]. PMID- 2884621 TI - Deletion of a DNA sequence in eight of nine families with X-linked ichthyosis (steroid sulphatase deficiency). AB - Deficiency of steroid sulphatase (STS) is associated with ichthyosis, with failure of the placental production of oestriol in late pregnancy and with difficulties in childbirth. The STS gene has been localised by deletion mapping to the distal tip of the snort arm of the X chromosome, and is of interest in that it appears to escape X-inactivation. We have constructed an X-specific DNA library and screened it for single copy DNA sequences which lie at the distal end of Xp. The sequence GMGX9 was found to map in the interval Xp22.3-pter and to detect a frequent HindIII polymorphism. We have used GMGX9 in linkage studies in families with classical X-linked ichthyosis and this has not only shown tight linkage with STS deficiency but has also revealed that the sequence is deleted in affected males in eight of nine families. GMGX9 is present in all of 26 normal male individuals so far examined. Our findings suggest that a high proportion of the mutations at the STS locus leading to enzyme deficiency are deletions, presumably generated by unequal cross-over events in female meiosis or by illegitimate X-Y interchange in male meiosis. PMID- 2884622 TI - A procedure for selective full length cDNA cloning of specific RNA species. AB - A method allowing routine establishment of full length and functionally competent cDNA clones of particular mRNAs from small preparations of polyadenylated RNA is described. Pairs of synthetic primers are used for first and second strand synthesis. They include sequences complementary to the 3' terminal regions of the mRNAs and of the full length first cDNA strands, respectively and bear a few additional nucleotides at their 5' ends. After synthesis of both cDNA strands in one tube, they are precisely trimmed back with T4 DNA polymerase in presence of only two nucleoside triphosphates, to yield sticky ends fitting into a vector plasmid cleaved with two restriction endonucleases. The procedure was first applied to the simultaneous cloning of all five major measles virus (MV) mRNA species from a persistently infected cell line. Two thirds of all clones contained full length MV-specific cDNAs. Screening of less than 200 clones was sufficient to obtain several independent clones corresponding to each mRNA, except for gene F which was represented only once. PMID- 2884624 TI - Phosphorylation of a 60 kDa polypeptide from Xenopus oocytes blocks messenger RNA translation. AB - The stored mRNP particles of Xenopus oocytes contain protein kinase activity and two major phosphoproteins of 60 kDa (pp60) and 56 kDa (pp56). These proteins can be phospholabelled in the particles either in vivo or in vitro and then isolated by SDS-PAGE. On renaturing pp60 in the presence of globin mRNA, a stable RNA protein complex is formed. The complex has a uniform density in Cs salt gradients, corresponding to the binding of about 10 protein molecules to each mRNA, probably at the poly(A) sequence. Compared with uncomplexed mRNA, the RNP complex is translated poorly both in vitro and in vivo. Translation of the complex can be regained after treatment with protein phosphatase. It is shown that dephosphorylation destabilizes the binding of protein to RNA, making the mRNA accessible for translation. Studies with native mRNP particles show that their translation also can be enhanced by dephosphorylation. PMID- 2884623 TI - A novel GC-rich dispersed repeat sequence in Drosophila melanogaster. AB - A novel family of dispersed repeat sequences from Drosophila melanogaster is described. Sequence analysis of two members of this family show them to contain greater than 75% GC bases. These are comprised of multiple repeats of GGX triplets interspersed occasionally with CGPy and TTPy. Southern blotting shows that these repeats are not transposable elements. Twenty four homologous recombinants have been localised by in situ hybridization to seven sites in the Drosophila genome. Polyadenylated RNAs homologous to this repeat family are expressed in a complex pattern which is developmentally regulated. We suggest that this family encodes a set of glycine-rich domains in Drosophila proteins. PMID- 2884625 TI - Identification of 28 DNA fragments that detect RFLPs in 13 distinct physical regions of the short arm of chromosome 5. AB - A series of 175 lambda phage carrying human inserts isolated from a library that is specific for the short arm of human chromosome 5 (5p) have been regionally mapped on 5p using a deletion mapping panel of 16 human-hamster cell hybrids, each of which contains a chromosome 5 with a different deletion in the short arm. Seventy-five single copy DNA fragments were screened with 12 restriction enzymes for their ability to detect restriction fragment length polymorphisms (RFLPs). Twenty-eight of these DNA fragments, which are located in 13 distinct physical regions of 5p, were found to detect RFLPs. These DNA markers make it possible to construct a linkage map that will span the entire length of 5p and will allow the relationship between genetic and physical distance for this region of the genome to be examined at a high level of resolution. PMID- 2884626 TI - The pea mitochondrial ATPase subunit 9 gene is located upstream of the ATPase alpha-subunit gene. PMID- 2884627 TI - An anonymous single copy X-chromosome clone DXS94 from Xq11-q21 identifies a common RFLP. PMID- 2884628 TI - Single copy X-chromosome clone p8 from Xq11-Xq13 identifies further low frequency RFLP [HGM8 no. DXS1]. PMID- 2884629 TI - Three RFLPs are detected by an alpha spectrin genomic clone. PMID- 2884630 TI - Apa I polymorphism of a human immunoglobin VH3 subclass locus. PMID- 2884631 TI - Multiple RFLPs at the human cholesteryl ester transfer protein (CETP) locus. PMID- 2884632 TI - An RFLP close to the human collagen I gene COL1A1. PMID- 2884633 TI - A restriction fragment length polymorphism at the murine c-myb locus. PMID- 2884634 TI - Bgl II polymorphism for the alpha 1-antitrypsin-related gene on chromosome 14. PMID- 2884635 TI - RFLP for the human LDL receptor gene (LDLR): Bst EII. PMID- 2884636 TI - Characterization of a highly polymorphic region 5' to JH in the human immunoglobulin heavy chain. AB - A cloned DNA segment 1.25 kilobases (kb) upstream from the joining segments of the human heavy chain immunoglobulin gene revealed extensive polymorphic variation at this locus, and the polymorphic pattern was stably transmitted to the next generation. Genomic restriction analysis showed that the polymorphism was caused by insertions/deletions within an MspI/BamHI fragment. Sequencing of one allele, 848 base pairs (bp) long, revealed eleven 50-base-pair tandem repeats. A second allele, 648 bp long, was cloned from a human genomic cosmid library, sequenced, and found to contain four fewer repeats than the first allele. A survey of 186 chromosomes from unrelated individuals of primarily northern European descent revealed at least six alleles. PMID- 2884638 TI - Hypervariable lengths of human DNA associated with a human satellite III sequence found in the 3.4kb Y-specific fragment. PMID- 2884637 TI - Nearly identical members of the heterogeneous IAP gene family are expressed in thymus of different mouse strains. AB - Poly(A)RNAs prepared from the thymuses of C57BL/6J and DBA/2J mice were used to construct cDNA libraries in the bacterial expression vector lambda gt11. The libraries were scanned first for protein production with polyvalent antiserum prepared against the 73kDa gag protein of mouse intracisternal A-particles (IAP). Reactive plaques were crossed-screened by hybridization with an IAP-specific DNA probe. Two IAP-specific protein-producing plaques were obtained from the C57BL/6 library and 4 from the DBA/2 library. One C57BL/6 cDNA clone (B12) and two DBA cDNA clones (D8 and D20) were sequenced in their entirety. Clones B12 and D8 were remarkably similar, particularly when compared to the 6 other IAP elements that have been sequenced thus far. We discuss the evidence which leads us to suggest that these clones may be derived from allelic IAP elements expressed in mouse thymus. PMID- 2884639 TI - A polymorphic DNA probe located to human chromosome 4p16 (D4S62). PMID- 2884640 TI - An anonymous DNA segment (II227) maps to the long arm of human chromosome 5 and identifies a BstXI polymorphism (D5S26). PMID- 2884641 TI - A c-DNA probe for the oncogene c-MEL (pC7-1) recognises a polymorphism with NcoI. PMID- 2884642 TI - A subclone of the autosomal phosphoglycerate kinase pseudogene (HGM8 gene symbol PGK1P2), localized to 6p23-q12, detects moderately polymorphic RFLP. PMID- 2884643 TI - SacI RFLP recognized by a human immunoglobulin kappa light chain constant region probe. PMID- 2884644 TI - Somatostatin prevents the desensitizing action of growth hormone-releasing factor on growth hormone release. AB - We have investigated the effect of prior exposure to somatostatin (SRIF) alone or in combination with growth hormone-releasing factor (GRF) on the subsequent cyclic AMP and GH responses to GRF in rat anterior pituitary cells in primary culture. The maximal 4.5-fold stimulation of GH release induced by a 3-hr incubation with GRF is reduced by 60% following a prior 3-hr exposure to 30 nM GRF. A 3-hr preincubation with GRF in the presence of 30 nM SRIF doubles spontaneous GH release while the maximal amount of GH released during a subsequent 3-hr exposure to GRF is similar to that measured in cells pretreated with control medium, thus completely preventing the loss of GH responsiveness induced by prior exposure to GRF. The prevention by SRIF of the desensitizing action of GRF on GH release is not observed on the cyclic AMP response which remains almost completely inhibited in GRF-pretreated cells. Similar protective effects are obtained when SRIF is incubated with prostaglandin E2 (PGE2), thus completely preventing the desensitizing action of PGE2 on GH release. Prior treatment with pertussis toxin completely prevents the protective action of SRIF on GH responsiveness. Pretreatment with GRF + SRIF increases by 85 and 60% the maximal amount of GH release induced by cholera toxin and 8-bromoadenosine 3',5' monophosphate, respectively. The post-SRIF rebound effect on GH release occurs mainly during the first 30 min following withdrawal of the tetradecapeptide. The present data demonstrate that simultaneous preincubation with SRIF and GRF prevents the marked inhibition of GH release during subsequent exposure to GRF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884645 TI - Somatostatin 28(1-12) in a somatostatin-secreting human medullary thyroid carcinoma cell line. AB - We have identified a system, the TT human medullary thyroid carcinoma cell line, which we found to contain 31.3 +/- 27.7 ng of somatostatin 28(1-12) immunoreactivity/mg protein. Radioimmunoassay of gel filtration fractions showed that the major form of immunoreactive somatostatin 28(1-12) had a molecular weight of 1,500 daltons. During reversed-phase high pressure liquid chromatography, this 1,500-dalton species coeluted with synthetic somatostatin 28(1-12). Somatostatin 28(1-12) containing forms larger than 7,000 daltons were also observed. Further studies will be required to elucidate the route of processing of prosomatostatin. The fact that the products of prosomatostatin processing in these cells are similar to those in normal tissues indicates that the TT medullary thyroid carcinoma cell line constitutes a useful model for human somatostatin gene expression. PMID- 2884646 TI - Neuropeptide and monoamine components of the parabrachial pontine complex. AB - The present investigation examined the distributions of immunoreactive neurotensin (NT), cholecystokinin octapeptide (CCK), substance P (SP), methionine enkephalin (ENK), vasoactive intestinal polypeptide (VIP), somatostatin (SS), rat neurophysin II (RNP II), vasopressin (VP), oxytocin (OXY), tyrosine hydroxylase (TH), and serotonin in the parabrachial nuclear complex (PB) of the rat. All of these substances were localized to the PB and they appeared to be chemoarchitecturally organized within the complex. The lateral subdivision (PBL) was organized medial-lateral and ventral-dorsal. Specifically NT, CCK, and SP immunoreactive fibers were found to be the most dense in the ventral aspect of the PBL. The distribution of NT-containing fibers was similar to the pattern of CCK-containing fibers and these were localized primarily to the central zone of the PBL. Immunoreactive SP fibers and cells were found in the external and internal zones ventrally and surrounding the dorsal and dorsolateral nuclei in the PBL. Somatostatin, ENK and VIP were found to be the most dense in the dorsal PBL. Serotonin- and TH-containing cells and fibers were found in both the PBL and PBM. These results, coupled with the observations of neuronal connections of the PB and the known functions of this region, underscore the potential involvement for these neuropeptides and monoamines in limbic-brainstem mechanisms of autonomic control. PMID- 2884647 TI - Immunoreactive dynorphin-A in bovine anterior pituitary and its in vitro release. AB - The anterior lobe (AL) of the bovine pituitary contained and released, during in vitro culture, a form of immunoreactive dynorphin-A (ir-DYN-A) larger than that occurring in neural tissue. Bovine AL tissue from intact females contained less ir-DYN-A than did AL tissue from castrated males. Enzymatically dispersed AL cells contained and released ir-DYN-A in vitro. Preincubation of dispersed AL cells for 18 hr, rather than 1.5 hr, increased the content and release of ir-DYN A as well as LH. Addition of gonadotropin-releasing hormone (GnRH) to tissue slices or dispersed cells stimulated release of LH, but in contrast to published observations from rat AL, GnRH had no effect on release of ir-DYN-A. Addition of estradiol-17 beta, with or without progesterone, increased release of ir-DYN-A but not LH during 2-hr cultures. In summary, bovine AL contains and releases in vitro a large molecular weight form of ir-DYN-A. Although this ir-DYN-A was not coreleased with LH, a reproductive role was suggested by in vivo and in vitro effects of gonadal hormones on ir-DYN-A in the bovine anterior pituitary. PMID- 2884648 TI - Immunoreactive dynorphin-A in ovine anterior pituitary and effects of estradiol 17 beta administration. AB - Anterior lobe (AL) tissue of the ovine pituitary gland contained a form of immunoreactive dynorphin-A (ir-DYN-A) larger than that found in pituitary neurointermediate lobe. Administration of estradiol-17 beta or estradiol-17 beta plus progesterone to ovariectomized sheep decreased AL tissue concentrations of ir-DYN-A but did not affect any LH parameter. Enzymatically dispersed AL cells also contained ir-DYN-A, but specific release during in vitro incubation was too low to be detected even when cells were exposed to gonadotropin-releasing hormone. PMID- 2884649 TI - Immunohistochemical analysis of the effects of cysteamine on somatostatin-like immunoreactivity in the rat central nervous system. AB - The brain and spinal cord of untreated and cysteamine-treated rats were analyzed with immunohistochemistry using antisera raised against somatostatin (SOM)-28(1 14) and SOM-28(15-28). Sections incubated with increasing dilutions of antiserum were evaluated subjectively on coded slides and with computer-assisted image analysis. For control experiments, antisera raised against methionine-enkephalin, neuropeptide Y (NPY) and dynorphin (DYN)(1-13) were used. The latter antiserum does not visualize the conventional DYN systems in the brain, but reacts with an unknown epitope, which here could be shown to be present in SOM neurons. In cysteamine-treated rats a marked decrease in SOM-28(15-28)-like immunoreactivity (1.1) could be recorded subjectively at all antibody concentrations in fibers in several brain areas, including nucleus accumbens, tuberculum olfactorium and the hypothalamic ventromedial and arcuate nuclei. In these areas SOM-LI is fairly weak in untreated rats. In SOM-rich regions such as the median eminence and the dorsal horn of the spinal cord, the depleting effect of cysteamine could be recorded subjectively only when diluted antisera were used. Image analysis confirmed the subjective analysis, and, in addition, differences between controls and cysteamine-treated rats could be shown also at high antiserum concentrations. SOM-28(15-28)-immunoreactive cell bodies could be seen in the brains of either control or drug-treated rats. No effect of cysteamine could be observed when antiserum raised to SOM-28(1-14) was used. Cysteamine did not seem to affect enkephalin-LI, NPY-LI or an epitope in SOM neurons reacting with DYN(1-13) antiserum. After preabsorption of SOM-28(15-28) antiserum with SOM-28(15-28) peptide, the staining patterns described above disappeared completely. However, if the SOM-28(15-28) peptide was pretreated with a high concentration (1 M) of cysteamine before being used for absorption with SOM antiserum, no blocking effect could be observed. The present results demonstrate with immunohistochemistry that cysteamine causes depletion of SOM-28(15-28) in fibers but apparently not in cell bodies. No effects on SOM-28(1-14)-LI were observed. This supports earlier evidence that cysteamine interacts with the disulphide bond in the SOM-28(15-28) molecule. The present results also emphasize that when analyzing drug effects on peptide neurons with immunohistochemical techniques, it is important to use dilution series of antibodies and preferably to carry out the analysis with objective image analysis methods. PMID- 2884650 TI - [Effect of various beta-adrenolytic drugs on respiratory function in patients with primary arterial hypertension]. PMID- 2884651 TI - Ultrastructure and immunohistochemistry of the lateral prostate in aged rats. AB - Ultrastructural, histological, and immunohistochemical studies were performed on lateral prostates of 1) aged rats from different strains, 2) rats permitted different levels of sexual activity, and 3) castrated rats. Antibodies against the following proteins were used as immunohistochemical markers: SVS II from seminal vesicle, LP 28 from lateral prostate, acid phosphatase isoenzymes from ventral prostate, transglutaminase from coagulating gland, and a commercial monoclonal antibody against cytokeratin. SVS II is a marker of lateral prostatic secretion, while immunoreactions to LP 28 and acid phosphatase (pI 7.1) were cytoplasmic. In aged animals the amount of intracellular secretion is decreased, and focally metaplastic transformation can be visualized by using immunohistochemical markers. Epithelial ultrastructure varied considerably with experimental conditions. Intensive sexual activity resulted in increased polymorphism and increased number of secretory granules within the glandular cells, while castration was followed by a rapid loss of secretory material. Also, in rats older than 10 months, a reduction in the number of secretion granules was common. The epithelium developed a positive immunoreaction to transglutaminase antibodies that were not observed in juvenile glands. Cells, presumably macrophages, which had an intense immunoreactivity for transglutaminase, were increased in number both within and outside the prostatic acini of aged rats. The possible interaction between secretory SVS II, a substrate of transglutaminase, the release of this enzyme from macrophages or its reflux from coagulating glands, the spontaneous cellular exfoliation that is due to decreased androgen levels, and dietary noxae may be of importance in the development of lateral prostatic nonbacterial inflammation in aged rats. PMID- 2884652 TI - Alpha adrenergic regulation of celiac blood flow and plasma catecholamine response during acute heat stress in fed cockerels. AB - Hubbard cockerels with chronically implanted electromagnetic blood flow probes on the celiac artery were used to establish a relationship between changes in postprandial celiac mean blood flow (MBF) and plasma catecholamines during a acute heat exposure. Five min after the elevation of ambient temperature from 25 to 37 C, there were concomitant reductions (P less than .05) in celiac MBF, norepinephrine (NE), and heart rate (HR). After 50 min of heat stress, rectal temperature (Tr), respiratory rate (RR), plasma epinephrine (E), and celiac vascular resistance (CVR) were significantly greater (P less than .05) than preheat stress thermoneutral control values. During the thermoneutral recovery period, all parameters returned to values comparable to preheat exposure control with the exception of NE, which tended (P less than .1) to remain lower. To determine the role of the sympathetic nervous system in regulating postprandial celiac MBF during acute heat exposure, chronically instrumented cockerels were infused with phenoxybenzamine, an alpha-adrenergic receptor-blocking agent. Alpha receptor blockade attenuated both postprandial intestinal hyperemia under thermoneutral conditions as well as the heat-induced reduction of postprandial celiac MBF. The results of these studies implicate the sympathetic nervous system in the regulation of postprandial celiac MBF in heat-stressed cockerels and indicate a possible alpha-adrenergic-mediated mechanism involved in postprandial intestinal hyperemia. PMID- 2884653 TI - Interactions between morphine-like analgesics and anticonvulsant drugs. AB - The effect of pretreatment with morphine-like analgesics on the anticonvulsant effect of phenytoin and phenobarbital against electroconvulsions and of phenobarbital and ethosuximide against pentetrazole-induced convulsions was studied in mice. High doses of morphine (4 mg/kg subcutaneously), fentanyl (100 micrograms/kg subcutaneously), pethidine and pentazocine (4 and 8 mg/kg subcutaneously) increased the anti-electroshock effect of phenytoin; that of phenobarbital was likewise increased by morphine (2 and 4 mg/kg), fentanyl (25 100 micrograms/kg) and pentazocine (2-8 mg/kg), whereas pethidine had no corresponding effect. There was no consistent effect of pretreatment with the analgesics studied on the anticonvulsant effects of phenobarbital and ethosuximide in the pentetrazole seizure threshold test. PMID- 2884654 TI - Differential effects of the dopamine antagonist remoxipride on apomorphine induced behaviour in the rat. AB - The effects of the novel substituted benzamide remoxipride on apomorphine induced behaviour in rats was investigated by means of an automatic holeboard apparatus. The ability of remoxipride to antagonise locomotion and gnawing induced by a high dose of apomorphine (5 mg/kg) and inhibition of exploration induced by a low dose of apomorphine (0.05 mg/kg) was tested. It was found that remoxipride in moderate doses potentiate locomotion and inhibit gnawing induced by the high dose of apomorphine while higher doses of remoxipride inhibits both apomorphine induced gnawing and locomotion. The inhibition of exploration following the low dose of apomorphine was not antagonised by remoxipride pretreatment. The results demonstrated that remoxipride has an interesting and unique profile of dopamine antagonistic effects in rat behavioural models. PMID- 2884655 TI - Aryl sulphatase isoenzymes of chorionic villi: implications for prenatal diagnosis. AB - Prenatal diagnosis of metachromatic leucodystrophy (MLD) is based on demonstrating a deficiency of aryl sulphatase A (ASA) in the fetus. To evaluate the place of chorionic villus sampling for prenatal diagnosis of this condition, the properties of ASA were compared in chorionic villi and cultured skin fibroblasts. Considerable differences with respect to pH optimum, Km values and linearity with incubation time were found. These differences can be explained by the presence of aryl sulphatase C (ASC), a major component in chorionic villi and placenta. This isoenzyme was shown to have activity towards p-nitrocatechol sulphate (NCS) thereby interfering in the colorimetric assay most often used to detect MLD (Baum et al., 1959) PMID- 2884657 TI - [Occurrence of tardive dyskinesia during neuroleptic treatment]. AB - The incidence of tardive dyskinesia under neuroleptic treatment is diversely estimated. The effectiveness of anticholinergics in its prevention is under discussion. Among 52 patients treated with neuroleptics for more than 5 years (mean: 9 years) only 2 developed tardive dyskinesia, and the disorder was transient in each case. The low doses of neuroleptic drugs administered and their systematic association with anticholinergics seem to be partly responsible for this low incidence of tardive dyskinesia. PMID- 2884656 TI - [Can respiratory tolerance to beta-blockers be predicted?]. AB - Adverse effects on respiratory function is one of the main problems associated with the use of beta-adrenoceptor antagonists. Studies on this subject in healthy volunteers or patients with obstructive airway disease have been performed by measuring air flow at rest and after exercise, but no attention has been paid to the repercussions on pulmonary circulation. The lack of standardized protocol, the inhomogeneity of groups and the absence of long-term studies preclude objective comparisons between the different beta-adrenoceptor antagonists. On the whole, cardioselective beta-blockers are better tolerated than the others, but any classification based on the respiratory effects to cardiovascular effectiveness ratio is, for the moment, impossible to establish. PMID- 2884658 TI - [Neuropathy in patients treated with almitrine]. PMID- 2884659 TI - [Diabetes with transient hypoinsulinosecretion in periarteritis nodosa. Possible role of pancreatic vasculitis]. PMID- 2884660 TI - Transcriptional regulation of the tyrosine hydroxylase gene by glucocorticoid and cyclic AMP. AB - Glucocorticoid and cyclic AMP increase tyrosine hydroxylase (TH) activity and mRNA levels in pheochromocytoma cultures. The transcriptional activity of the TH gene, as measured by nuclear run-on assay, is also increased when cultures are treated with the synthetic glucocorticoid dexamethasone or agents that increase intracellular cyclic AMP, such as forskolin and 8-BrcAMP. Both inducers effect transcriptional changes within 10 min after treatment and are maximal after 30 min for forskolin and after 60 min for dexamethasone. The 5' flanking sequences of the TH gene were fused to the bacterial gene chloramphenicol acetyltransferase (CAT), and the hybrid gene was transfected into pheochromocytoma cultures and GH4 pituitary cells. In both cell lines, a region of the TH gene containing bases 272 to +27 conferred induction of CAT by cyclic AMP, but not by glucocorticoid. The same results were found when a region of the TH gene containing -773 to +27 was used. Thus, the sequences required for induction of TH by cyclic AMP are contained within 272 bases of 5' flanking sequence, but sequences sufficient for glucocorticoid regulation are not contained within 773 bases. PMID- 2884661 TI - Effector and suppressor circuits of the immune response are activated in vivo by different mechanisms. AB - The application of fluorescein isothiocyanate (FITC) onto the skin of mice induces a contact hypersensitivity immune response. Lymph nodes draining the skin painted with FITC contain fluorescent cells that induce contact hypersensitivity to FITC when injected into normal mice. The antigen-presenting cells responsible for activating the effector pathway of the contact hypersensitivity response express Ia histocompatibility determinants and are resistant to inactivation with gamma-radiation. Exposing the skin to low doses of UV radiation (280-320 nm) before the application of FITC suppresses the contact hypersensitivity response to FITC. Cells present in the draining lymph nodes of these mice induce suppressor T lymphocytes when injected into normal recipients. The inducer cells in the draining lymph nodes are Thy 1+, Ia- and are inactivated by gamma radiation. These studies demonstrate that different mechanisms are involved in the in vivo activation of effector and suppressor immune responses, and they suggest that the mode of initial antigen presentation determines which immunologic circuit will be activated in response to a contact-sensitizing antigen. PMID- 2884662 TI - Hematopoietic cell transplantation in murine globoid cell leukodystrophy (the twitcher mouse): effects on levels of galactosylceramidase, psychosine, and galactocerebrosides. AB - Hematopoietic cell transplantation (HCT) prolongs survival in the twitcher mouse, an authentic animal model of human globoid cell leukodystrophy (Krabbe disease; galactosylceramidase deficiency), but the effects of HCT on levels of galactosylceramidase, psychosine, and cerebrosides in the tissues of twitcher mice have not been previously studied. Galactosylceramidase was less than 8% of control activity in tissues of untreated twitcher mice but reached normal values in brain and spleen and 20-30% of control in kidney of 100-day-old twitchers that received HCT at age 10 days. Using a recently developed method for the simultaneous determination of psychosine and cerebrosides, we measured the tissue levels of these lipids in the above animals. The levels of psychosine in brain, sciatic nerve, and kidney of untreated twitcher mice were 44, 200, and 12 times control values, respectively, in 30-day-old animals and 69, 500, and 14 times control levels in 40-day-old mice. On the other hand, levels of cerebroside were approximately 35% of control values in sciatic nerve, remained about the same in the brain, and were elevated 10-fold in the kidney of twitcher mice. After HCT, psychosine levels in the brains of 30-day-old twitchers were lowered to 30-35% of values in untreated twitchers, and the levels remained in that range during the post-HCT period. Similarly, brain cerebroside levels remained low in HCT-treated twitcher mice. Although psychosine levels in sciatic nerves of HCT-treated twitcher mice increased more slowly than in the nerves of untreated twitchers, the levels in 100-day-old HCT-treated twitcher mice had reached the same high values as those seen in untreated 40-day-old twitchers. It is not known whether the extremely high levels of psychosine in sciatic nerves ultimately contribute to the death of twitcher mice after HCT. PMID- 2884664 TI - The effects of cyanide on intracellular ionic exchange in ferret and rat ventricular myocardium. AB - The effects of cyanide on Ca2+ exchange in isolated ventricular myocytes and on the intracellular concentrations of Ca2+, Na+ and H+ have been investigated to assess the contribution that mitochondria might play in cellular Ca2+ metabolism. Ionic levels were measured with ion-selective electrodes. KCN (2.5 mM) inhibited a component of Ca2+ exchange in myocytes that could be attributed to mitochondrial exchange, but was without effect on non-mitochondrial Ca2+ exchange. NaCN (2.5 mM) caused a transient reduction of [H+]i, [Na+]i and [Ca2+]i when applied to the superfusate bathing ventricular trabeculae or papillary muscles. The transient changes of [Na+]i were accentuated when the preparation was exposed to a solution which would be expected to increase the cellular calcium content. The reduction of [Na+]i which accompanies a reduction of the extracellular sodium concentration, [Na]o, was attenuated in the presence of NaCN, but the intracellular acidosis resulting from a reduction of [Na]o was unaffected by NaCN. A small, but significant, rise of [Ca2+]i accompanied a reduction of [Na]o but only when NaCN was present in the superfusate. It is concluded that cyanide ions have a reasonably specific action on cardiac cellular ionic metabolism. Its primary action is to prevent mitochondrial Ca2+ sequestration. It is postulated that a Na+/H+ exchange, possibly at the sarcolemma, could account for some of the changes to sarcoplasmic ionic levels observed. In a solution of low [Na]o, it is concluded that mitochondria could sequester at least 30% of the calcium accumulated by the cell even though the sarcoplasmic [Ca2+] does not exceed 0.3 microM. PMID- 2884663 TI - N-methyl-D-aspartate receptor antagonist desegregates eye-specific stripes. AB - The optic tecta of surgically produced three-eyed tadpoles were chronically exposed to the N-methyl-D-aspartate (NMDA) receptor antagonist aminophosphonovaleric acid (APV), or to NMDA itself, to assess the influence of NMDA receptor/channels on the eye-specific segregation of retinal ganglion cell (RGC) terminals that occurs whenever two retinas innervate one tectal lobe. Exposure of the tectum to the active isomer of APV produces desegregation of the RGC terminals without blocking electrical activity in the afferents or altering their terminal arbor morphology. Exposure to the inactive isomer of APV causes no perturbation of the normal stripe pattern. APV-induced desegregation is completely reversible within 2 weeks of removal of the APV. In addition, exposure of the optic tectum to NMDA results in stripes with sharper borders and fewer forks and fusions than untreated animals. These results suggest that the NMDA receptor/channel plays a role in eye-specific segregation in the three-eyed tadpole. PMID- 2884665 TI - Dynamic mechanism of visual accommodation in teleosts: structure of the lens muscle and its nerve control. AB - The accommodatory system was examined in two teleosts (mackerel and bass). The fine structure and innervation of the lens muscle is presented to characterize the muscle organization. The neural pathway involved in the dynamic accommodation was examined by analysing the fibre spectrum of the ciliary nerve, and the nerve that controls the lens-muscle activity was studied by means of electrical stimulation. The lens muscle is composed of smooth-muscle cells, which contain numerous mitochondria. Many synaptic endings are also found on the muscle cells; these synaptic endings contain many agranular vesicles. From the results of the fibre analysis, it was found that the nerve that controls the lens muscle contains less than 100 myelinated nerve fibres in both fish: the electrical stimulation experiments demonstrate that the muscle is controlled by oculomotor (parasympathetic) nerve fibres. Ultrastructural features of the lens muscle and its nerve control resemble those of the mammalian ciliary muscle. The teleostean lens muscle is classified as a multi-unit smooth muscle. PMID- 2884666 TI - The Leeuwenhoek lecture, 1985. A molecular biologist's view of viral hepatitis. AB - Three forms of viral hepatitis can be distinguished serologically. Hepatitis A virus is a picornavirus, which is being studied increasingly after its propagation in cell cultures. The B virus (HBV) is the prototype of a family now termed hepadna viruses and is by far the best understood. The third, by exclusion, is non-A non-B, about which little else is known. Molecular cloning methods enable copies of viral genes to be propagated and analysed quite readily and provide the means for isolation and expression of individual genes in microbial and animal cells. Determination of the nucleotide sequences of HBV DNA revealed its genetic organization and so guided studies of the mechanism of gene expression both in infected animals and cultures of transformed cells. Replication of the viral genome has also been studied in natural infections, particularly with duck HBV, but also with the human virus. Expression of HBV genes in microbial cells is valuable as a source of antigens for diagnostic reagents and vaccine preparations, but has also been of consequence for the identification of viral gene products not previously recognized and which are of considerable current interest. The methods and materials now available provide additional opportunities for inquiring into the course of viral infection, replication of the virus and, for HBV, the possible role in the development of hepatomas of integration of the viral genome into the host chromosome. PMID- 2884667 TI - The Florey lecture, 1986. Vaccine prevention of virus-induced human cancers. AB - Carcinogenic viruses have been discovered in numerous animal species over the last 80 years but their role in human cancer has only recently become an important issue. With EB virus involved with endemic Burkitt's lymphoma and undifferentiated nasopharyngeal carcinoma, hepatitis B virus with primary liver cancer, papilloma viruses with carcinoma of the cervix, and T-cell leukaemia virus with adult T leukaemia, 20-25% of all human cancer appears to have a virus component in its causation. By analogy with certain virus-induced animal cancers, vaccine prevention of infection should greatly reduce subsequent tumour development; vaccines against hepatitis B virus are already on trial for this purpose in populations at risk. Experiments are described in which an EB virus subunit vaccine consisting of the virus-determined membrane antigen glycoprotein molecule of molecular mass 340 kDa (MA gp340) has been prepared by two purification methods. Material from one of these has successfully protected cotton-top tamarins against a 100% lymphomagenic dose of challenge virus and investigations are under way to identify an immunogen, based on MA gp340, suitable for use in man. Genetically engineered bacterial, yeast, and mammalian cells expressing the gp340 gene are already available; this gene has also been inserted into vaccinia and varicella virus vectors. Powerful new adjuvants are also considered, together with future strategies for human vaccine studies. PMID- 2884668 TI - Excitation-contraction coupling and extracellular calcium transients in rabbit atrium: reconstruction of basic cellular mechanisms. AB - Interactions of electrogenic sodium-calcium exchange, calcium channel and sarcoplasmic reticulum in the mammalian heart have been explored by simulation of extracellular calcium transients measured with tetramethylmurexide in rabbit atrium. The approach has been to use the simplest possible formulations of these mechanisms, which together with a minimum number of additional mechanisms allow reconstruction of action potentials, intracellular calcium transients and extracellular calcium transients. A 3:1 sodium-calcium exchange stoichiometry is assumed. Calcium-channel inactivation is assumed to take place by a voltage dependent mechanism, which is accelerated by a rise in intracellular calcium; intracellular calcium release becomes a major physiological regulator of calcium influx via calcium channels. A calcium release mechanism is assumed, which is both calcium- and voltage-sensitive, and which undergoes prolonged inactivation. 200 microM cytosolic calcium buffer is assumed. For most simulations only instantaneous potassium conductances are simulated so as to study the other mechanisms independently of time- and calcium-dependent outward current. Thus, the model reconstructs extracellular calcium transients and typical action potential configuration changes during steady-state and non-steady-state stimulation from the mechanisms directly involved in trans-sarcolemmal calcium movements. The model predicts relatively small trans-sarcolemmal calcium movements during regular stimulation (ca. 2 mumol kg-1 fresh mass per excitation); calcium current is fully activated within 2 ms of excitation, inactivation is substantially complete within 30 ms, and sodium-calcium exchange significantly resists repolarization from approximately -30 mV. Net calcium movements many times larger are possible during non-steady-state stimulation. Long action potentials at premature excitations or after inhibition of calcium release can be supported almost exclusively by calcium current (net calcium influx 5-30 mumol kg-1 fresh mass); action potentials during potentiated post stimulatory contractions can be supported almost exclusively by sodium-calcium exchange (net calcium efflux 4-20 mumol kg-1 fresh mass). Large calcium movements between the extracellular space and the sarcoplasmic reticulum can take place through the cytosol with virtually no contractile activation. The simulations provide integrated explanations of electrical activity, contractile function and trans-sarcolemmal calcium movements, which were outside the explanatory range of previous models. PMID- 2884669 TI - Beta-adrenergic agonists and cyclic AMP decrease intracellular resting free calcium concentration in ileum smooth muscle. AB - Intracellular free-calcium levels were measured in strips of longitudinal smooth muscle from guinea-pig ileum; fura-2 was used as a calcium monitor. At rest the calcium concentration was about 180 nM, and this rose to 300-400 nM following electrical stimulation and during spontaneous calcium transients (all measurements at 23-25 degrees C). Isoprenaline suppressed the spontaneous calcium transients, and reduced the resting calcium level to about 130 nM. This fall in resting calcium concentration was seen even in muscle strips which did not have spontaneous activity. Elevation of intracellular cyclic AMP levels, produced by forskolin or dibutyryl cyclic AMP, mimicked the actions of isoprenaline. We conclude that the relaxant effects of beta-adrenergic agonists of visceral smooth muscle may be explained partly by a fall in intracellular resting free-calcium level, mediated via an increase in cyclic AMP. PMID- 2884670 TI - A mass-accumulation of vertebrates from the Lower Cretaceous of Nehden (Sauerland), West Germany. AB - A 'fauna' of vertebrates recovered from a cavern-like deposit at a quarry near the village of Nehden in Sauerland is described and reviewed in some detail. Anatomical descriptions of some skeletal elements are given, where they provide new information or supplement previous descriptions. The clays in which the fossils were buried have been dated comparatively as Aptian (late Lower Cretaceous) and approximately contemporary with the Weald Clay unit of the Wealden Formation of southeast England and the Bernissartian of southwest Belgium. Both these latter formations have yielded faunal and floral assemblages that are very similar to those found at Nehden. The vertebrates collected at Nehden include adult and numerous juvenile remains of two species of the ornithischian dinosaur Iguanodon: I. atherfieldensis and I. bernissartensis. (I. atherfieldensis is the more abundantly represented.) These can be contrasted with the mass-accumulation of Iguanodon recovered from Bernissart, where these dinosaurs are represented by predominantly adult skeletons. There is circumstantial evidence from a documented association of bones (revealed by examination of excavation plans) to support a reconstruction of a juvenile Iguanodon bernissartensis with a body length ca. 2-3 m (fully grown individuals reach a body length of ca. 11 m); this is the smallest individual of this species recovered to date. The remainder of the vertebrate assemblage consists of very fragmentary remains of crocodilians, chelonians and extremely rare fish. The presence of both a hypsilophodontid ornithischian dinosaur and a theropod saurischian dinosaur must be viewed as extremely conjectural, based as they are on two very poor specimens. Remains referred to as Vectisaurus sp. in previous accounts of this site are juvenile individuals of Iguanodon. The circumstances surrounding three mass-accumulations of fossils, Trossingen, Bernissart and Nehden, are reviewed, and evidence of mass deaths among recent vertebrates is considered. Archive records at Trossingen suggest that periodic events, such as mud-slides, may have been partly responsible for the concentration of remains. Similar events may also have been responsible for the assemblages at Bernissart and Nehden; the assemblage at Nehden may represent an accumulation caused by a flash flood or by a herd crossing a river. It is suggested that awareness of such common phenomena should be emphasized when data such as these are used in estimations of numerical abundance and diversity of species in the fossil record.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2884671 TI - Acanthonus armatus, a deep-sea teleost fish with a minute brain and large ears. AB - Acanthonus armatus, a deep-water benthopelagic fish, has, per unit body weight, the smallest brain and largest semicircular canals of any known teleost and possibly any vertebrate. Pertinent areas of the brainstem and the cerebellum are large; this observation suggests that the fish's lateral line and vestibular senses are particularly acute. The huge cranial cavity also contains heavy saccular otoliths, which may indicate that the fish is sensitive to low-frequency sound. Brain size and specialization are consistent with an apparent pattern of low energy requirement, hovering and slow movement over the deep-sea floor, and consumption of small benthic prey in a dark environment. PMID- 2884672 TI - The evolution of visual processing and the construction of seeing systems. AB - This paper is concerned with the evolution of visual mechanisms and the possibility of copying their principles at different levels of sophistication. It is an old question how the complex interaction between eye and brain evolved when each needs the other as a test-bed for successive improvements. I propose that the primitive mechanism for the separation of stationary objects relies on their relative movement against a background, normally caused by the animal's own movement. Apparently insects and many lower animals use little more than this for negotiating through a three-dimensional world, making adequate responses to individual objects which they 'see' without a cortical system or even without a large brain. In the development of higher animals such as birds or man, additional circuits store memories of the forms of objects that have been frequently inspected from all angles or handled. Simple visual systems, however, are tuned to a feature of the world by which objects separate themselves by movement relative to the eye. In making simple artificial visual systems which 'see', as distinct from merely projecting the image, it is more hopeful to copy the 'ambient' vision of lower animals than the cortical systems of birds or mammals. PMID- 2884673 TI - An account of responses of spectrally opponent neurons in macaque lateral geniculate nucleus to successive contrast. AB - Coloured surfaces in the normal environment may be brighter or dimmer than the mean adaptation level. Changes in the firing rate of cells of the parvocellular layers of macaque lateral geniculate nucleus were studied with such stimuli; chromatic mixtures briefly replaced a white adaptation field. This paradigm is therefore one of successive contrast. Families of intensity-response curves for different wavelengths were measured. When taking sections at different luminance ratios through these families of curves, strongly opponent cells displayed spectrally selective responses at low luminance ratios, while weakly opponent cells had higher chromatic thresholds and responded well to stimuli at higher luminance ratios, brighter than the adaptation field. Strength of cone opponency, defined as the weight of the inhibitory cone mechanism relative to the excitatory one, was thus related to the range of intensity in which cells appeared to operate most effectively. S-cone inputs, as tested with lights lying along tritanopic confusion lines, could either be excitatory or inhibitory. Families of curves for different wavelengths can be simulated mathematically for a given cell by a simple model by using known cone absorption spectra. Hyperbolic response functions relate cone absorption to the output signals of the three cone mechanisms, which are assumed to interact linearly. Parameters from the simulation provided estimates of strength of cone opponency and cone sensitivity which were shown to be continuously distributed. Cell activity can be related to cone excitation in a trichromatic colour space with the help of the model, to give an indication of suprathreshold coding of colour and lightness. PMID- 2884674 TI - Acetylcholine may regulate its own nicotinic receptor-channel through the C kinase system. AB - Acetylcholine (ACh)-activated channel properties were examined on an aneural culture of chick embryo myotubes by using patch-clamp techniques. Changes in conductance, open time and closed time were induced by the selective activator of the calcium- and phospholipid-dependent C-kinase (PKc), 12-O-tetradecanoylphorbol 13-acetate (TPA). The action of TPA was mimicked by exogenous phospholipase C and was blocked by the PKc inhibitor, 1-(5-isoquinolinylsulphonyl)-2-methyl piperazine. In addition to its gating action, ACh was shown to stimulate phosphoinositide turnover and to translocate PKc from the cytosol to the cell membrane. Both these ACh-induced effects were inhibited by curare and not substantially affected by atropine. Bath-applied ACh outside the patch-pipette in the cell-attached patch-clamp mode, had a strong effect on the ACh-activated channels in the patch membrane, in a way that resembled the action of TPA. These findings raise the possibility that ACh regulates its own nicotinic receptors through the C-kinase system. PMID- 2884675 TI - Adenosine antagonizes the histamine-induced stimulation of human atrial myocardium: protection by H1-receptor blockade. AB - The inotropic effect of histamine on the human myocardium consists of two opposing components: positive, H2-mediated, and negative, H1-mediated. Because adenosine is known to antagonize histamine H2-responses, we assessed whether adenosine may unmask H1-mediated histamine responses in human myocardium. We found that adenosine modulates the stimulatory effects of histamine on pectinate muscles isolated from human right atrium and converts them as a function of its concentration from positive to negative. Further, histamine potentiated the tendency of adenosine to induce cardiac arrest. The H1-blocker pyrilamine antagonized the adenosine-induced suppression of the positive inotropic and chronotropic effects of histamine. Thus, our data indicate that the negative inotropic and chronotropic effects of histamine in the presence of adenosine result in part from an antagonism of H2-mediated increases in rate and contractility, and in part from an unmasking of H1-mediated decreases in the same parameters. Adenosine and histamine may be co-released in response to hypoxia or ischemia. In spite of the protection that adenosine may afford the human myocardium against excessive histamine stimulation, adenosine may also unmask the inhibitory actions of histamine, promoting dysrhythmia, and negative inotropic and chronotropic effects. PMID- 2884676 TI - Modulation of neurotransmitter release by adenosine and ATP. PMID- 2884677 TI - Tunicate Thy-1--an invertebrate member of the Ig superfamily. PMID- 2884678 TI - Dose-dependent pharmacokinetics of a xanthine-related nootropic drug, ethimizol, in rats. AB - Pharmacokinetics of the respiratory analeptic ethimizol, 4,5-bis(methylcarbamoyl) 1-ethylimidazole, with recently recognized nootropic properties, its metabolite 4 carbamoyl-5-methylcarbamoyl-1-ethylimidazole and of two metabolites of unknown structure was studied in plasma of rats after intravenous administration of the [2-14C]-labelled compound in 5 doses: 1.1, 3.3, 10, 20, and 30 mg/kg. The apparently monoexponential time course of dose normalized ethimizol plasma concentrations were not superimposable and the derived pharmacokinetic parameters were dose-dependent. The elimination rate constant and the initial volume of distribution decreased with increasing dose. The AUC versus dose relationship displayed disproportionate increases with increasing dose. Plasma ethimizol failed to obey the Michaelis-Menten kinetics and in an attempt to rationalize the observed nonlinearity a complete competitive product inhibition was suggested. Similar to the parent drug, the three metabolites exhibited a distinctly dose dependent behavior as could be deduced from their dose-normalized concentration time curves. PMID- 2884679 TI - Pharmacokinetics and excretion of unique beta-adrenergic agonists. AB - beta-Adrenergic agonist analogs (congeners) of isoproterenol in which the N isopropyl group has been linked to a p-methyl- (119) or p-trifluoromethyl- (143) anilide moiety through a four carbon methylene spacer have been investigated with respect to their plasma pharmacokinetic profiles and biliary and urinary elimination characteristics in rats. In spite of the differences in selectivity of pharmacologic effects and durations of action between these unique beta adrenergic agonists and isoproterenol, no differences were observed in their pharmacokinetic parameters in plasma after intravenous administration. Plasma clearances were rapid (67-78 ml/min) and the compounds were widely distributed. In contrast to the known elimination characteristics of isoproterenol, biliary excretion was the major pathway for elimination of 119 and 143. Parent drug and 'one' major metabolite peak appeared in HPLC chromatograms of bile collected from rats that received 119 and 143 by intravenous administration. Preliminary evidence suggests that this metabolite peak consists of one or more glucuronide and/or sulfate conjugates. Urinary excretion appears to be of lesser quantitative importance for 119 and 143 than for isoproterenol. The protracted duration of residence of the derivatives in the heart may help to explain the unusual effects and tissue-specific pharmacological properties of these unique beta-adrenergic agonists. PMID- 2884680 TI - Effects of spasmogens on relaxant dose-response curves to full or partial agonists at beta-adrenoceptors of guinea pig isolated trachea. AB - When guinea pig isolated trachea is contracted with either carbachol or methacholine, relaxant concentration-response curves to isoprenaline, salmefamol and fenoterol were shifted to the right, compared with curves obtained with either spontaneous or histamine-induced tone. Carbachol and methacholine also reduced the maximal relaxation to fenoterol and abolished relaxations to the partial agonist pindolol. It is concluded that the processes linking receptor to contractile response in trachea are different for histamine receptors and muscarinic cholinoceptors. PMID- 2884681 TI - Treatment of akathisia with lorazepam. An open clinical trial. AB - Sixteen patients with neuroleptic-induced akathisia were treated with lorazepam. A marked improvement in symptoms was observed in 9 of the patient and moderate improvement in 5. Symptoms remained unchanged in 2 patients. The drop in the akathisia score from a pretreatment value of 1.81 to 0.5 after 7 days and to 0.32 after 14 days was statistically significant. Symptoms did not improve significantly during observation of the spontaneous course. No severe side effects were observed. The physiologic mechanisms of action of lorazepam on the akathisia syndrome are discussed. PMID- 2884682 TI - Subjective effects during administration and on discontinuation of zopiclone and temazepam in normal subjects. AB - The purpose of the study was to ascertain whether the new hypnotic, zopiclone, was likely to produce rebound problems after short-term use, in comparison with placebo and a standard hypnotic, temazepam, and whether tapering the dosage lessened any such effects. Ten normal v olunteer subjects were administered 5 treatment sequences, each lasting 4 weeks, using a balanced design, with at least 2 weeks between sequences. The treatment sequences were: (table: see text) Each drug was given at night before retiring to bed. Daily ratings comprised a Sleep Questionnaire, Mood Rating Scales, the Spielberger State Anxiety Inventory and Bodily Symptom Scales. Both drugs improved quality of sleep but their discontinuation was followed by some worsening which was postponed but not avoided by halving the dosage for a week. Speed of, and feeling on, awakening showed discontinuation effects with temazepam but not with zopiclone. Zopiclone was associated with feelings of being troubled, tense, antagonistic and bored whereas temazepam produced drowsiness, clumsiness, dreaminess and sadness. Some increase in these ratings was noted after stopping temazepam and these were less after having the dosage. Zopiclone was associated with minimal such effects. For bodily symptoms, zopiclone produced some headache, a metallic taste, and some blurring of vision; temazepam induced nausea, memory impairment and pins and needles. Withdrawal effects on bodily symptom ratings were inconsistent and not affected by tapering off the dose. In conclusion, the administration of zopiclone tends to be associated with some dysphoric effects, temazepam with sedation. Rebound effects are minimal with zopiclone and reducing the dosage gradually does not seem necessary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884683 TI - Dopaminergic antagonists potentiate the adenohypophyseal growth reaction to oestrogen: thioridazine is less effective than perphenazine. AB - The injection of oestradiol benzoate as an aqueous microcrystal suspension, in a dose of 1 mg twice a week, evokes a marked adenohypophyseal growth reaction in male rats. The reaction is potentiated by dopaminergic antagonists from the group of neuroleptics (specifically perphenazine and thioridazine). Elicitation of the same adenohypophyseal reaction required twice as much thioridazine (10 mg/rat per day) as perphenazine. Thyroxine inhibited the adenohypophyseal growth reaction to oestradiol. The serum polyphenol oxidase (ceruloplasmin) level rose after oestradiol and perphenazine and thioridazine slightly potentiated the increase. PMID- 2884684 TI - Systematic desensitization and relaxation as adjuncts in the treatment of anorexia nervosa: a preliminary study. PMID- 2884685 TI - GABA uptake is inhibited by thyroid hormones: implications for depression. AB - Studies of the effects of thyroid hormones on the uptake of neurotransmitters by homogenates of rat cerebral cortex have revealed a significant competitive inhibition of neuronal uptake of [3H]GABA by thyroid hormones (T3 greater than T4 greater than rT3). The IC50 for inhibition of GABA uptake by T3 was estimated at 4 microM and that of T4 at 11 microns. GABA uptake in homogenates of cerebral cortex from hypothyroid rats was significantly enhanced over that of controls; however, uptake in tissues from hyperthyroid rats was not significantly diminished. PMID- 2884686 TI - Elevated plasma luteinizing hormone concentrations, cryptorchidism and mania. AB - A young man with acute mania and unilateral cryptorchidism had plasma luteinizing hormone (LH) concentrations that were much higher than the maximum LH concentrations we have found in normal subjects and patients with schizophrenia. Plasma concentrations of testosterone and sex hormone binding globulin were not abnormal, showing that the elevated plasma LH concentrations were probably due to increased secretion of LH-releasing hormone (LHRH). This case supports our previous results which suggest that an abnormally high secretion of LHRH, due presumably to an abnormality in central neurotransmission, may be a feature of acute mania in young men. PMID- 2884687 TI - Provocative tests with psychostimulant drugs in schizophrenia. AB - The psychotogenic effects of psychostimulant drugs have provided a major line of evidence in support of the DA hypothesis of schizophrenia. To evaluate the effects of psychostimulant (PS) drug in schizophrenia and the clinical variables which may influence their expression, we reviewed 36 studies of PS drugs in patients with schizophrenia. Approximately 40% evidence a psychotogenic response to PS administration in doses that are subpsychotogenic in normals. Specific clinical variables appear to modify this response, including diagnosis, degree and type of psychopathology, stage of illness and pharmacologic status at the time of testing. Non-amphetamine-like PS drugs, e.g., methylphenidate, appear to have greater psychotogenic potency than amphetamine-like PS drugs. These results suggest the presence of a subgroup of schizophrenic patients who exhibit psychotic symptom activation with PS in a state dependent or independent fashion. This biologic phenomenon may be clinically exploitable and should be investigated further. PMID- 2884688 TI - Psychotropic effects of adrenergic beta-blockers on agonistic behavior between resident and intruder mice. AB - The present study was conducted to investigate the effect of adrenergic beta blockers on agonistic behavior in male mice, using quantitative ethological methods. Agonistic behavior was evoked using a resident-intruder paradigm. The following drugs were administered orally at four dose levels (vehicle, 5, 10 and 20 mg/kg) to either resident or intruder mice: dl-propranolol, practolol, d propranolol, and l-propranolol. When the resident was treated with either dl propranolol or l-propranolol, aggressive episodes (offensive sideways posture, attack bite, tail rattle) were suppressed significantly in a dose-dependent manner, whereas practolol and d-propranolol were ineffective. All treatments except the high dose of l-propranolol failed to affect the resident's solitary behavior (locomotion). When the intruder was treated with beta-blockers, agonistic behavior was not altered. Since practolol does not cross the blood brain barrier, the differential suppression of agonistic behavior is due to the central action of beta-blockers. d-Propranolol does cross the blood-brain barrier but is devoid of beta-receptor blocking property; hence l-propranolol suppression of agonistic behavior implies inactivation of brain adrenergic beta-receptors. The findings seem to indicate that beta-blockers such as dl-propranolol and l propranolol have a psychotropic action. PMID- 2884689 TI - Comparison of the effects of chlordiazepoxide and CL 218,872 on serum corticosterone concentrations in rats. AB - Fifteen minute exposure to a novel environment plus 120 dB sound stimulation produced a three-fold increase in serum corticosterone concentrations in rats. A low dose of intraperitoneally (IP) administered chlordiazepoxide (CDP) (5 mg/kg) attenuated this response, whereas a higher dose (20 mg/kg) elevated corticosterone concentrations in rats not subjected to sound stress. Parallel results were obtained after intracerebroventricular (ICV) drug administration, with a low dose of CDP (5 micrograms) reducing the sound stress response and higher doses (25 and 50 micrograms) increasing corticosterone concentrations in unstressed animals. Thus, despite the presence of benzodiazepine (BDZ) receptors at every level of the hypothalamic-pituitary-adrenocortical axis, it appears that BDZs alter the activity of this system via an interaction with BDZ receptors in brain. CL 218,872 (2.5-20 mg/kg), a novel non-BDZ anxiolytic compound, did not attenuate the corticosterone elevation produced by sound stimulation, and also failed to alter baseline corticosterone concentrations in unstressed animals. The fact that CL 218,872 is a selective agonist for brain Type I BDZ receptors suggests that BDZs are not influencing corticosterone secretion through an interaction with this BDZ receptor subtype. Furthermore, these results indicate that stress (as measured by pituitary-adrenocortical activation) can be dissociated from anxiety (as measured by conflict paradigms), thus challenging the validity of the corticosteroid stress test as a screening procedure for anxiolytic activity. PMID- 2884690 TI - Partitioning of polar fatty acids into lymph and portal vein after intestinal absorption in the rat. AB - We tested the hypothesis that fatty acids destined for the portal vein after intestinal absorption would be diverted into lymph when infused along with a saturated long-chain fatty acid. Thoracic fistula rats were infused intraduodenally with either linolenic (18:3), lauric (12:0), or decanoic (10:0) acid, or with each fatty acid in combination with 5 mM palmitic acid (16:0), in micellar solutions of taurocholate (10 mM) and 2-mono-oleoylglycerol. Lymphatic transport of linolenic acid was enhanced by co-absorption with palmitic acid: when 0.1 mM linolenic acid was infused alone, 32 +/- 8% of that absorbed and transported beyond the mesentery was carried in lymph. The addition of palmitic acid to the infusate increased the percentage transported in lymph to 56 +/- 10% (P less than 0.005). The increment was due to enhanced intracellular re esterification of linolenate into triacylglycerol. When 5 mM linolenic acid was infused, the comparable figures for lymphatic transport were 55 +/- 2% for linolenate infused alone and 66 +/- 6% for linolenate infused with palmitate (P less than 0.005). In contrast, the predominantly portal venous transport of lauric and decanoic acids was unaffected by co-absorption with palmitate. We conclude that the partitioning of long-chain fatty acids between portal blood and lymph is dependent on the luminal milieu, in addition to polarity of the fatty acid and the rate of absorption. Unsaturated long-chain fatty acids have a substantial portal transport under conditions which simulate normal food ingestion. PMID- 2884691 TI - Effect of drugs, hormones and electrical field stimulation on isolated muscle strips from human choledochoduodenal junction. AB - The behaviour of in vitro strips from the human choledochoduodenal junction would appear to be related to the anatomical location of origin of the strip. Strips from the papillary region showed low tone and obvious spontaneous rhythmic contractions (0 X 5-6/min). Strips from the region of the inferior choledochal sphincter showed, in ten out of fifteen specimens, spontaneous myogenic tone and gave a relaxation or a biphasic response (relaxation followed by contraction) to electrical field stimulation (0 X 3 ms pulses at 10 Hz for 5 s). All strips from human choledochoduodenal junction are remarkably insensitive to a variety of gastrointestinal hormones and to opioid agents. PMID- 2884692 TI - Beta-adrenoceptor blocking drugs in therapy. PMID- 2884693 TI - Undescended testis: value of MR imaging. AB - Magnetic resonance (MR) imaging was performed in 32 male patients, 20 with no abnormalities and 12 with clinically suspected undescended testes. The results were compared with ultrasonographic, computed tomographic, clinical, and surgical findings. The undescended testes were unilateral in eight patients (one had testicular duplication) and bilateral in four. Of 16 undescended testes, 15 were correctly identified on MR images. One intraabdominal testis was not seen. Testis fat contrast at 0.35 T was optimal with a short repetition time (TR) and a short echo time (TE). At 1.5 T, good contrast was achieved with short TR/TE sequences, but the contrast was even more pronounced with even longer TR/TE parameters. In seven patients with unilateral undescended testes, the undescended and contralateral testes showed symmetrical tissue signal intensity on both T1- and T2-weighted images. In three, the undescended testis was of lower signal intensity, suggesting atrophy. MR imaging promises to become an important diagnostic tool in the detection of undescended testes. PMID- 2884694 TI - Expression of peptides and transmitters in neurons and expression of filament proteins in astrocytes in fetal cerebral cortical transplants to adult spinal cord. PMID- 2884695 TI - Adrenergic receptors mediating prostaglandin production in the rabbit vas deferens. AB - Contractile and prostaglandin E (PGE)-producing effects of adrenergic agonists were compared in the rabbit isolated vas deferens to determine which adrenergic receptor(s) potentially could mediate neural responses. Additionally, interactions among receptors were elucidated by comparing responses to norepinephrine, phenylephrine and isoproterenol to those in the presence of selective adrenergic agonists or antagonists. Norepinephrine increased the force of muscle contraction and the immunoassayable PGE concentrations in a concentration-dependent manner with EC50's of 55 +/- 8 and 112 +/- 39 microM, respectively. Propranolol (10 microM) enhanced the contractile effects of norepinephrine (p less than 0.01) whereas yohimbine (100 microM) or prazosin (1 microM) reduced norepinephrine-induced contractions and PGE production (p less than 0.01). Propranolol did not alter the PGE production induced by norepinephrine. Metoprolol (100 microM) also enhanced contractile effects of norepinephrine (p less than 0.05). The beta adrenergic agonist, isoproterenol (100 nM), decreased the contractile, but not the PGE-producing, effects of phenylephrine (p less than 0.001). Isoproterenol, given alone, increased PGE concentrations and inhibited electrically-induced force generation in a concentration-dependent manner. These results are consistent with the presence of alpha receptors on the vas deferens which mediate smooth muscle contraction and PGE generation. Beta receptors which mediate relaxation and PGE production also are present. Tentative identification of the beta receptor subtype revealed the presence of a beta 1 receptor. PMID- 2884696 TI - Prostacyclin as neuromodulator in the sympathetically stimulated rabbit heart. AB - Prostaglandin E2 (PGE2) has previously been shown to inhibit sympathetic neurotransmission in different organs and species. Based on this inhibitory effect and on its reversal by cyclo-oxygenase inhibitors, PGE2 has been claimed to be a physiological modulator of in vivo release of norepinephrine (NE) from sympathetic nerves. It is now recognized that prostacyclin (PGI2) is the main cyclo-oxygenase product in the heart. We therefore addressed the question whether PGI2, within the same preparation, is formed in increased amounts during sympathetic nerve stimulation and has neuromodulatory activity. The effluent from isolated rabbit hearts subjected to sympathetic nerve stimulation or to infusion of NE or adenosine (ADO) was collected, and its content of PGE2 and 6-keto-PGF1 alpha (dehydration product of PGI2) was analyzed using gas chromatography/mass spectrometry, operated in the negative ion/chemical ionization mode. Other hearts were infused with PGI2 and nerve stimulation induced outflow of endogenous NE into the effluent was analyzed using HPLC with electrochemical detection. Nerve stimulation at 5 or 10 Hz (before but not after adrenergic receptor blockade), as well as infusion of NE (10(-6)-10(-5)M) or ADO (10(-4)M) increased the cardiac outflow of 6-keto-PGF1 alpha. Basal and nerve stimulation induced efflux of 6 keto-PGF1 alpha was approximately 5 times higher than the corresponding efflux of PGE2. PGI2 dose-dependently inhibited the outflow of NE from sympathetically stimulated hearts, the inhibition at 10(-6)M being approximately 40%. On the basis of these observations we propose that PGI2 is a more likely candidate than PGE2 as a potential modulator of neurotransmission in cardiac tissue in vivo. PMID- 2884697 TI - Beta-adrenergic stimulation of gastrin release mediated by gastrin-releasing peptide in rat antral mucosa. AB - The present studies were directed to examine the effects of beta-adrenergic and cholinergic stimulation on gastrin release and to assess the potential role of gastrin-releasing peptide in exerting these effects, utilizing incubated rat antral mucosa. Rat antral mucosa was incubated at 37 degrees C in Krebs-Henseleit bicarbonate buffer, pH 7.4, continuously gassed with 95% O2-5% CO2. After 1 h media were sampled for radioimmunoassay measurement of gastrin content. Inclusion of carbachol (2.5 X 10(-6) M) in culture medium increased medium gastrin concentration by 106 +/- 28% (P less than 0.01); addition of specific antibodies to gastrin-releasing peptide to the culture medium did not affect carbachol stimulated gastrin release. Inclusion of isoproterenol (10(-9) M) in culture medium did not affect somatostatin release into the medium, but increased medium gastrin by 234 +/- 24% (P less than 0.001). However, in contrast to carbachol, addition of antibodies to gastrin-releasing peptide to culture medium decreased isoproterenol-stimulated gastrin release by 67 +/- 9% (P less than 0.001). Results of these studies indicate that, under the conditions of these experiments, beta-adrenergic, but not muscarinic, stimulation of gastrin release may be mediated, at least in part, through gastrin-releasing peptide. PMID- 2884698 TI - Dynorphin A immunoreactivity in human cerebrospinal fluid. AB - Dynorphin A immunoreactivity in human cerebrospinal fluid has been characterized. Large quantities of the fluid were fractionated by molecular sieving on a Sephadex G-50 column and analyzed by radioimmunoassay. Active fractions were further analyzed by means of HPLC and an enzyme radioimmunoassay procedure for identification of Leu-enkephalin-Arg6 sequences. Several dynorphin A-active components of varying sizes were identified. However, most immunoreactive material derived from species of higher molecular weight (Mr 3000 and 5000) than authentic dynorphin A (Mr 2000). The Leu-enkephalin core was found to reside in both these large structures. PMID- 2884699 TI - The regulation of basal pancreatic polypeptide levels in dogs. AB - In response to various stimuli, pancreatic polypeptide (PP) release is predominantly mediated by cholinergic mechanisms, and may be modulated by sympathetic and opiate (inhibitory) effects. However, the mechanisms regulating basal PP levels remain unclear. We examined the possible role of the sympathetic nervous system and endogenous opiates in the regulation of basal levels of pancreatic polypeptide in trained conscious dogs. During prolonged (150 min) alpha- or beta-adrenergic blockade with phentolamine and propranolol, separately or in combination, there was no change in the basal PP levels of 154 +/- 20 pg/ml. Effective adrenergic modulation of pancreatic hormones was evident since alpha blockade led to a rise in insulin and glucagon, beta blockade led to a fall in insulin and glucagon, while combined alpha- and beta-adrenergic blockade did not affect insulin or glucagon. Opiate blockade with naloxone (1.25 mg followed by 1 microgram/kg/min) led to a delayed fall in PP from 153 +/- 22 to 89 +/- 15 pg/ml at 90 min (no change by 30 min), without a change of insulin or glucagon. Infusion of a potent morphine analogue D-Met2-Pro5-enkephalinamide (0.5 microgram/kg/min) led to a sustained fall in PP to 91 +/- 8 pg/ml by 30 min without a change in insulin or glucagon. Somatostatin infusion (0.2 microgram/kg/min) with insulin and glucagon replacement, led to a similar sustained fall in PP. It is concluded that in dogs: in contrast to insulin and glucagon, at basal conditions the plasma level of PP is not modulated by endogenous alpha- or beta-adrenergic influences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884701 TI - [5-aminosalicylic acid treatment of ulcerative colitis during the acute phase in patients resistant or intolerant to salazopyrine]. PMID- 2884700 TI - [Conditions of intubation with vecuronium. Priming dose technic versus single bolus dose]. PMID- 2884702 TI - [Somatostatin in the treatment of hemorrhaging esophago-gastric varices. Controlled clinical trial in comparison with ranitidine]. PMID- 2884703 TI - Effect of various barbituric acid derivatives on survival of functional hepatocytes from adult rats in primary culture. AB - Eighteen barbituric acid (BA) derivatives and three structurally related chemicals (non-BA-derivatives) were tested for their potency in supporting survival of functional hepatocytes from adult rats in primary culture. Of the 18 BA derivatives, nine drugs showed excellent maintenance effect on hepatocyte survival and function. Although four BA derivatives were also effective, their potency was relatively lower. The remaining five BA derivatives and three structurally related chemicals exhibited no maintenance effect. Thus, a correlation was found between the BA derivative structure and the potency for supporting hepatocyte survival in primary culture. The dose response curves of hepatocyte survival were generally biphasic in shape, as a function of BA derivative concentration. The optimum concentrations for observing the morphological and biochemical effects of the BA derivatives differed from each other. The maintenance of hepatocytes was attained only in the continuous presence of the BA derivatives in the medium. The nine excellent BA derivatives efficiently prevented hepatocytes from morphological degeneration which was observed in the control cultures. The surviving hepatocytes in the presence of these BA derivatives showed higher albumin secretion and retained higher basal levels of tyrosine aminotransferase (TAT) activity for at least 2 weeks in primary culture, as compared with control. Furthermore, the addition of dexamethasone (10 microM) caused a 2- to 4-fold induction of TAT activity for at least 2-weeks in primary culture. PMID- 2884704 TI - Detection of Clostridium perfringens epsilon toxin by ELISA. AB - An enzyme-linked immunosorbent assay (ELISA) has been developed as an alternative to neutralisation tests in mice to detect Clostridium perfringens type D epsilon toxin in the intestinal contents of animals which have died from suspected enterotoxaemia. The test was sensitive and quantitative and gave excellent agreement with the mouse protection test. PMID- 2884705 TI - Action of tulobuterol and fenoterol on the mucociliary clearance. AB - The influence of tulobuterol and fenoterol upon mucociliary clearance (mC) and airway obstruction was investigated in 8 patients with chronic obstructive bronchitis and two patients with chronic bronchial asthma. The lung function and mC measurements were repeated after a 1-week random oral treatment with 4 mg tulobuterol/day or 7.5 mg fenoterol/day in a double-blind cross-over design. Tulobuterol and fenoterol improved mC of the total, central and peripheral bronchial tree significantly in comparison to the pretreatment values (p less than 0.001) reaching, after beta 2-agonist therapy, values observed in normal subjects. In comparison to no treatment and pretreatment with oral fenoterol, tulobuterol protected slightly better from the inhalative provocation with 99mTc radioactive erythrocytes used to measure mC. Inhalative fenoterol was more efficient than oral fenoterol or tulobuterol to reverse the bronchospastic part of airway obstruction. No differences of mean daily peak flows, systolic and diastolic systemic blood pressure measurements and pulse rate were recorded during tulobuterol and fenoterol treatment. Both drugs were tolerated without side effects. PMID- 2884706 TI - Broxaterol (Z.1170), a new oral beta 2-agonist compared with salbutamol. AB - The bronchodilating activity and tolerability of a single 0.5-mg oral dose of broxaterol (Z.1170) were evaluated in 18 patients with reversible bronchial obstruction. Salbutamol 4.0 mg and placebo were used as controls. The study design was double-blind within patients. The forced expiratory volume in 1 s (FEV1), pulse rate, and blood pressure were measured immediately before and 0.5, 1, 2, 3, 4, 5, and 6 h after each treatment. At the same time clinical controls were made to detect the possible presence of side effects. Both broxaterol and salbutamol caused significant increases in FEV1 until the 5th hour as compared to baseline values and until the 2nd hour as compared to placebo. No significant difference was reported between the effects of broxaterol and those of salbutamol at all the times considered. The tolerability of broxaterol was good, as was that of salbutamol. The pulse rate and blood pressure did not show any significant clinical variations. The side effect reported most frequently was tremor. PMID- 2884707 TI - Causes of elevated serum gamma-glutamyl transferase in patients attending outpatient somatic clinics and district health centres. AB - In this study of 1985 patients in somatic outpatient care (medicine, surgery, orthopedics, emergency and primary health care clinics), 231, or 11.6%, were found to have an elevated serum GT value (above 0.9 mukat/l). Alcohol was the cause of this in approximately one third of the cases, while diseases and drugs were the underlying cause in the other cases. In the population, there were 208 alcohol-overconsuming patients (163 men and 45 women) and 28 patients had a serum GT elevation which led to detection of a previous unknown alcohol problem or excessive consumption. The mean and median value for serum GT for the alcohol patients was markedly higher than in the non-alcohol-overconsuming group. The sensitivity for serum GT (with a value of 0.9) as regards alcohol consumption was 40%. The GT test screened 4.2% of patients with excessive alcohol consumption of which one third were "hidden". PMID- 2884708 TI - [Reconsideration of the vascular factor in gastric and duodenal ulcer]. PMID- 2884710 TI - [Involvement of the sympatho-adrenergic system in the regulation of gastric acid secretion and ulcerogenesis. Therapeutic consequences]. PMID- 2884709 TI - [Comparative study of the efficacy of ranitidine, cimetidine (Asiloc), De-Nol and spirulina in the treatment of gastric and duodenal ulcer]. PMID- 2884711 TI - [Treatment of gastroduodenal ulcer with ulcosilvanil]. PMID- 2884712 TI - [Comparative effects of Corinfar and Isoptin on gastric secretion in patients with gastric and duodenal ulcer]. PMID- 2884714 TI - [Clinical and morpho-functional considerations on liver cirrhosis in the elderly]. PMID- 2884715 TI - [Tumor markers in hepatic cancer]. PMID- 2884713 TI - [The role of the sympathetic nervous system in the regulation of gastric function]. PMID- 2884716 TI - [The immune compartment in chronic active liver disease responsive and non responsive to corticoid therapy]. PMID- 2884717 TI - [Chemical neuroanatomy: a new understanding of the functions of the nervous system]. PMID- 2884718 TI - [Clinical examination of the foot--medicolegal implications]. PMID- 2884719 TI - [Chronic cough and gastroenterology]. PMID- 2884720 TI - [Bioclinical pneumology conference of Laennec Hospital. Case 6: April 1985. Long term hemoptysis and inflammatory syndrome in a 29-year-old woman]. PMID- 2884721 TI - [Myocardial revascularization using both internal mammary arteries. Analysis of 94 cases]. PMID- 2884722 TI - [TaqI restriction polymorphism and the HLA-B27 allele in ankylosing spondylitis]. AB - The restriction polymorphism Taq I of the 3.5 kb fragment of Class I HLA sequences is tested in patients suffering from ankylosing spondylarthritis, with or without antigen HLA B27. In a reference population, the frequency of this polymorphism is higher than that of allele B27. All B27 individuals, ill or not, present the polymorphic band, also present in some individuals B12. The distribution of this band is studied, in unrelated individuals serotyped for HLA B as well as members of families with spondylarthritis. The presence of the variable 3.5 kb band is not automatically correlated with the gene of the disease in corresponding individuals. PMID- 2884723 TI - [Treatment of ankylosing spondylitis with salazosulfapyridine. A controlled double-blind study in 60 patients]. AB - The efficacy of salazosulfapyridine (SI) has been recently reported in the course of peripheral arthritis in ankylosing spondylarthritis (SPA), but is action on the axial forms of the disease was not known. We have therefore conducted a therapeutic trial in 60 patients suffering from SPA, without peripheral involvement clinical sign evoking an enterocolopathy. This double-blind study compared the activity of SI at a dose of 2 g/day with a placebo, for 6 months. Thirteen patients had to discontinue the treatment: 6 in the placebo group (inefficacy: 3 cases, anemia: 1 case, epigastric pain: 1 case, rash: 1 case) and 7 cases in the SI group (inefficacy: 2 cases, nauseous: 3 cases, abdominal pain: 1 case, moderate elevation of transaminases: 1 case). These 13 patients were kept for the global analysis and considered as therapeutic failures. The treatment was considered effective in 15 out of 30 patients of group SI and in 30 patients on placebo (p less than 0.02). In addition, in group SI, a statistically significant decrease of the daily dose of non-steroid anti-inflammatory drugs was observed ( 6.5 +/- 7.2 versus -2.4 +/- 6.4 in the placebo group, p less than 0.05); also was observed a decrease of the functional index (-5.9 +/- 6.6 versus -1.9 +/- 5.7 in the group placebo, p less than 0.05) and of the serum level of immunoglobulin G ( 1.8 +/- 3.6 g/l versus +0.8 +/- 2.9 in the placebo group, p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884724 TI - Clinical experience of the tolerance of mesalazine and olsalazine in patients intolerant of sulphasalazine. AB - We assessed the tolerance and safety of two new preparations designed to release 5-aminosalicylic acid in the colon in patients with ulcerative colitis who were intolerant of sulphasalazine. Twenty-eight of 37 patients (76%) given mesalazine and 18 of 21 patients (86%) given olsalazine tolerated the new preparations with no adverse effects. No haematologic or biochemical abnormalities were detected. Adverse reactions to the new preparations were usually but not always similar to those they had previously encountered with sulphasalazine, but a few patients experienced rash and diarrhoea. In some patients intolerant of one of the new preparations, their tolerance of the other was assessed. Three patients intolerant of mesalazine tolerated olsalazine. Similarly, three other patients intolerant of olsalazine tolerated mesalazine. We conclude that not all adverse effects of sulphasalazine are due to the sulphapyridine part of the molecule. Some are due to the released 5-aminosalicylic acid and some to the parent compound. Both drugs are likely to prove useful in the management of patients intolerant of sulphasalazine. PMID- 2884725 TI - [Findings: small testicles]. AB - Small testicles are normal in prepubertal boys, irrespective of their height and weight. Small testicles associated with premature sexual development (pseudopuberty) usually reflect an alternate source of androgens, most frequently adrenal (e.g. in congenital adrenogenital syndrome). Small testicles as a result of testicular atrophy are either the consequence of a painful event such as mumps orchitis or trauma (such as torsion), or a side effect of extratesticular disease (such as liver cirrhoses, chronic alcoholism, haemochromatosis, Curschmann Steinert dystrophic myotonia etc.). Certain drugs (e.g. immunosuppressive and chemotherapy) and irradiation may also lead to testicular atrophy. Cryptorchidism as the expression of prenatal testicular damage may lead to an "incompetent", i.e. small, testis even if properly descended by surgery. However, a small testis after orchidopexy may also be the consequence of injury to blood vessels during surgery. The cryptorchid testis has an increased though still low incidence of malignancy, but a markedly elevated rate of sterility. Probably the most frequent cause of small testicles is Klinefelter syndrome (XXY/47), involving a wide spectrum from eunuchoid hypogonadism to a normally virilized albeit sterile male, in whom gynecomastia is not much more frequent than in the average male population but in whom the mammary cancer risk is definitely elevated almost to female rates. PMID- 2884726 TI - Homeo boxes in the study of development. AB - The body plan of Drosophila is determined to a large extent by homeotic genes, which specify the identity and spatial arrangement of the body segments. Homeotic genes share a characteristic DNA segment, the homeo box, which encodes a defined domain of the homeotic proteins. The homeo domain seems to mediate the binding to specific DNA sequences, whereby the homeotic proteins exert a gene regulatory function. By isolating the normal Antennapedia gene, fusing its protein-coding sequences to an inducible promoter, and reintroducing this fusion gene into the germline of flies, it has been possible to transform head structures into thoracic structures and to alter the body plan in a predicted way. Sequence homologies suggest that similar genetic mechanisms may control development in higher organisms. PMID- 2884727 TI - Biochemistry of information storage in the nervous system. AB - The use of molecular biological approaches has defined new mechanisms that store information in the mammalian nervous system. Environmental stimuli alter steady state levels of messenger RNA species encoding neurotransmitters, thereby altering synaptic, neuronal, and network function over time. External or internal stimuli alter impulse activity, which alters membrane depolarization and selectively changes the expression of specific transmitter genes. These processes occur in diverse peripheral and central neurons, suggesting that information storage is widespread in the neuraxis. The temporal profile of any particular molecular mnemonic process is determined by specific kinetics of turnover and by the geometry of the neuron resulting in axonal transport of molecules to different synaptic arrays at different times. Generally, transmitters, the agents of millisecond-to-millisecond communication, are subject to relatively long lasting changes in expression, ensuring that ongoing physiological function is translated into information storage. PMID- 2884728 TI - Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. AB - An efficient strategy for mapping human genes that cause recessive traits has been devised that uses mapped restriction fragment length polymorphisms (RFLPs) and the DNA of affected children from consanguineous marriages. The method involves detection of the disease locus by virtue of the fact that the adjacent region will preferentially be homozygous by descent in such inbred children. A single affected child of a first-cousin marriage is shown to contain the same total information about linkage as a nuclear family with three affected children. Calculations show that it should be practical to map a recessive disease gene by studying DNA from fewer than a dozen unrelated, affected inbred children, given a complete RFLP linkage map. The method should make it possible to map many recessive diseases for which it is impractical or impossible to collect adequate numbers of families with multiple affected offspring. PMID- 2884729 TI - Genetic abnormalities as biological tumor markers. PMID- 2884730 TI - Gastric rupture and death caused by ipecac syrup. AB - We have reported a fatal complication of a therapeutic dose of ipecac syrup administered in a hospital emergency room. This child received 15 ml of ipecac syrup shortly after ingesting one to five tablets of chlorpheniramine maleate (4 mg). A prolonged course of vomiting (more than 24 hours) eventually resulted in gastric rupture and death. While the use of ipecac is both efficacious and safe in the overwhelming majority of cases, there have been documented fatalities after appropriate doses. For this reason, ongoing education for physicians is important; education of parents is also warranted since wide-scale distribution to families is the accepted standard. Because most patients stop vomiting within two to three hours after ipecac administration, we recommend that children with persistent vomiting should be observed in a medical facility, where electrolyte levels can be measured and fluids can be replaced if necessary. PMID- 2884731 TI - [Clinical significance of the determination of the gamma glutamine transferase enzyme in the diagnosis of liver and biliary tract diseases]. PMID- 2884732 TI - Elevated glutamic acid values in a malnourished patient. A case report. AB - Routine serum and cerebrospinal (CSF) amino acid estimations were carried out on a patient with pellagra and malnutrition. Urea levels were low and serum and CSF ammonia levels elevated. A remarkable observation was that the serum glutamic acid level rose to 44.9 times normal, which is far higher than any value reported in the medical literature. At this stage no explanation for this rise is known. Similarly no explanation can be given for the posttreatment elevation of the CSF proline levels to 13.8 times above normal. PMID- 2884733 TI - [Pruritus in chronic uremic patients in periodic hemodialysis. Treatment with terfenadine (an antagonist of histamine H1 receptors)]. PMID- 2884735 TI - [New basic preparations with prolonged action in the treatment of rheumatoid arthritis]. AB - A long-term comparative study of the classic basic drug-d-Penicillamin and 2 new sulfa drugs: sulfasalazin and salazopyridazin used for the first time in rheumatology, was conducted. Both drugs were shown to produce a "basic" effect in rheumatoid arthritis and to exceed d-Penicillamin in their therapeutic action. Better results were obtained with salazopyridazin. The tolerance to the new antirheumatic sulfa drugs was quite satisfactory; no severe side-effects were noted. Both drugs extend the potentialities of antirheumatoid therapy of prolonged action and warrant further use and study. PMID- 2884734 TI - Autogenous parathyroid grafts for generalized primary parathyroid hyperplasia: contrasting outcome in sporadic hyperplasia versus multiple endocrine neoplasia type I. AB - Sixteen patients with generalized primary parathyroid hyperplasia were treated with attempted total parathyroidectomy and placement of an autogenous parathyroid graft in the forearm musculature; these patients have been followed for up to 79 months. We assessed completeness of parathyroidectomy on the basis of the background immunoreactive parathyroid hormone (iPTH) value 3 to 7 days after surgery, which predicted the chance of a graft-independent recurrence or persistence of hyperparathyroidism (0/8 if undetectable versus 4/5 if normal or high). Total parathyroidectomy was sometimes difficult to achieve because of the presence of supernumerary or ectopic parathyroid glands; to enhance the success rate of total parathyroidectomy, we suggest both the use of preoperative ultrasonography to locate intrathyroidal parathyroids and a routine search for supernumerary parathyroids that includes transcervical thymectomy. Graft function was monitored by measuring the secretory gradient for iPTH (the difference between the two antecubital fossae). Gradients on postoperative days 3 to 7 were barely detectable, but by 3 weeks, larger iPTH gradients were noted in every case. By 4 months, the graft could maintain normal serum calcium levels in all but one case. Autonomous graft function has evolved in four of six evaluable patients with type I multiple endocrine neoplasia (MEN I), but in none of the nine patients with sporadic hyperplasia (p = 0.043). A prospective study is needed to determine whether the use of a smaller number of parathyroid fragments for the autogenous graft in known MEN I patients might delay recurrence. PMID- 2884736 TI - Evaluation of the Chernoff/Kavlock test for developmental toxicity. Proceedings of the Workshop on the Chernoff/Kavlock Short Term In Vivo Developmental Toxicity Test. Cincinnati, Ohio, May 20 and 21, 1986. PMID- 2884737 TI - Short-term developmental toxicity testing: considerations in the validation process. AB - The development and validation of short-term tests that assess developmental toxicity have received increased attention due to the large number of agents that need to be tested and the desirability to reduce the overall use of animals in research and safety evaluation. The Short-Term In Vivo Reproductive Toxicity Test was developed to help meet this need and to provide a method for prioritizing agents for further testing. This report provides a brief overview of the risk assessment process and a focus on the aspects of test validation that should be considered when evaluating short-term tests. It is intended to give the reader an appreciation for many of the considerations that must go into developing and validating a short-term test, and to indicate areas within the risk assessment process where inclusion of such a test may be appropriate. PMID- 2884738 TI - Application of the preliminary developmental toxicity screen for chemical hazard identification under the Toxic Substances Control Act. AB - The Office of Toxic Substances (OTS) within the U.S. Environmental Protection Agency (EPA) is authorized to carry forth the mandates of the Toxic Substances Control Act (TSCA). Included among the provisions of TSCA are the development of requirements for testing of "new" and "existing" chemicals that may present an unreasonable risk of injury to health or the environment. There are over 63,000 "existing" chemicals on the TSCA inventory, and EPA in recent years has been receiving an average of over 1,300 submissions for "new" chemicals a year. Since it is illogical and unrealistic to expect that all of these chemicals should be subjected to detailed testing for all potential adverse health and environmental effects, OTS views screening assays as highly useful tools to assign priorities to chemicals for further testing according to standard methodologies. The Chernoff/Kavlock assay (preliminary developmental toxicity screen) was specifically developed to address the need for a developmental toxicity assay to prioritize for further testing the large number of "new" and "existing" chemicals. OTS has been involved in seeking the development of data through the preliminary developmental toxicity screen for purposes of validating the screen and to obtain critical data necessary for evaluating chemicals. OTS believes that the screen has a role in the risk assessment process and has developed a testing protocol, which is included along with other OTS test guidelines; has provided internal guidance on when the screen may be recommended; and has discussed how the data may be applied in prioritizing chemicals for further study. PMID- 2884739 TI - Workshop on the Chernoff/Kavlock preliminary developmental toxicity test. AB - The Chernoff/Kavlock assay, proposed as a preliminary screen for teratogenic potential, was the subject of a 2-day workshop sponsored by the National Institute for Occupational Safety and Health. Data from three large testing programs were presented, representing tests of 165 chemicals, of which 33 were tested at least twice. Applications of the test in industrial laboratories and product development, hazard identification, and risk assessment were discussed. Workshop participants recognized the assay as one of several valid ways to preliminarily evaluate chemicals with unknown developmental toxicity. Other preliminary tests were also discussed in terms of their relationship to this test, which was seen as having the advantage of providing information on neonatal viability. Other techniques, particularly an abbreviated conventional teratology study, were also recognized as appropriate screens. The preferred test in a particular laboratory will be dependent upon the particular skills and objectives of that laboratory. Standardized protocols were suggested, but flexibility in experimental design was considered necessary, and many variations on the basic test could be appropriate. This preliminary test has been used most often as a single-dose test in mice, but might provide more generally useful data if conducted in rats using two dose levels. Workshop participants viewed the test as highly reliable in correctly identifying developmentally toxic chemicals and suggested that a negative finding in a properly conducted Chernoff/Kavlock test could be a sufficient basis for regulatory agencies to determine that conventional teratology tests in the same species are not warranted. PMID- 2884740 TI - A summary of the results of 55 chemicals screened for developmental toxicity in mice. AB - Fifty-five chemicals, including known teratogens, known embryotoxins, equivocal teratogens, nonembryotoxins, and nonteratogens, as well as compounds of unknown teratogenic or embryotoxic potential, were evaluated in the Chernoff/Kavlock developmental toxicity screen. All chemicals were administered by gavage to pregnant ICR/SIM mice on gestation days 8 through 12. The mice were allowed to deliver, and several neonatal growth and viability parameters were measured in the offspring. Comparative statistical analysis of these parameters between treated animals and concurrent (vehicle-treated) controls provided a data base to evaluate the validity of the developmental toxicity screen as an assay to detect teratogens and embryotoxins. Of the 26 compounds reported in the literature to be teratogenic or embryotoxic in mice following oral administration, 24 were positive in the developmental toxicity screen. Of the compounds previously tested in conventional assays and found to be devoid of teratogenic or embryotoxic activity in mice, 93% were negative in the developmental toxicity screen. The importance of experimental design, dose selection, and neonatal growth and viability measurements as they relate to interpretation and evaluation of the results of the developmental toxicity assay are discussed. PMID- 2884741 TI - Evaluation of 60 chemicals in a preliminary developmental toxicity test. AB - The number of chemicals in commerce which have not been evaluated for potential developmental toxicity is large. Because of the time and expense required by conventional developmental toxicity tests, an abbreviated assay is needed that will preliminarily evaluate otherwise untested chemicals to help prioritize them for conventional testing. A proposed short-term in vivo assay has been used in a series of studies in which a total of 60 chemicals were tested. Some were independently tested two or four times each. In this preliminary test, pregnant mice were dosed during mid-pregnancy and were then allowed to deliver litters. Litter size, birth weight, and neonatal growth and survival to postnatal day 3 were recorded as indices of potential developmental toxicity. Results in this assay and conventional mouse teratology tests were generally concordant. Conventional data were available for 14 chemicals (ten teratogens, one fetotoxin, three nonteratogens), of which 11 (nine teratogens, one fetotoxin, one nonteratogen) produced evidence of developmental toxicity. This included conventional data for three chemicals (ethylene glycol, diethylene glycol dimethyl ether, and triethylene glycol dimethyl ether) that were untested before the present study. As high priority candidates for conventional testing on the basis of results here, all were subsequently studied in a standard teratology assay and were confirmed to be teratogenic in mice. Additionally, one of them (ethylene glycol) plus a fourth high priority candidate for conventional study (diethylene glycol monomethyl ether) were subsequently tested in rats and were found to be teratogenic in that species. PMID- 2884742 TI - Recommendations for the statistical analysis of Chernoff/Kavlock test data. AB - The statistical analyses of the data related to the teratogenic testing of 60 compounds utilizing the Chernoff/Kavlock test are the basis of this paper. The hypotheses chosen to be tested and the statistical tests utilized to test those hypotheses are discussed. The topics explored are the use of comparisonwise error rate versus experimentwise error rate, the use of nonparametric tests versus more "conventional" parametric tests and the use of "historical data" in assessing and interpreting group difference. PMID- 2884743 TI - A comparison of developmental toxicity evident at term to postnatal growth and survival using ethylene glycol monoethyl ether, ethylene glycol monobutyl ether and ethanol. AB - This study was designed to compare an abbreviated evaluation of uterine contents at term (teratology probe) with a modified Chernoff-Kavlock assay (postnatal study), [Chernoff N, Kavlock RJ: J Toxicol Environ Health 10:541-550, 1982]. Mice were intubated during gestation and were evaluated for signs of toxicity. In the teratology probe, uterine contents were examined at term. In the postnatal study, offspring were examined and weighed through day 22 postpartum. Ethylene glycol monoethyl ether (EGEE) produced embryo lethality and malformations, and decreased fetal weight at a dose level which was not maternally toxic in the teratology probe. In the postnatal study, EGEE decreased litter size and neonatal body weight; while litter size continued to decrease beyond the neonatal period, body weights of surviving pups were not significantly different from control. Pups exposed prenatally to EGEE developed kinked tail which was not apparent in fetuses or neonates. Maternally toxic dose levels of ethylene glycol monobutyl ether and ethanol were associated with increased embryo lethality in teratology probe studies. In postnatal studies, there were no significant effects on pup growth or survival at maternally toxic dose levels. Preliminary conclusions regarding maternal and developmental toxicity were comparable based on the teratology probe or postnatal study. Both assays measure litter size and offspring weight, but the teratology probe measures resorption incidence which may be a more sensitive index of prenatal death than number of live born. Neither fetal weight nor neonatal weight reliably predict permanent alteration of growth. A postnatal study permits detection of internal malformations or functional defects which reduce postnatal survival and gross abnormalities which appear postnatally. PMID- 2884744 TI - Currently used alternatives to the Chernoff-Kavlock short-term in vivo reproductive toxicity assay. AB - The Chernoff-Kavlock assay was initially designed to identify developmental toxins within a relatively short time frame, using a mammalian system. Although it has been used for initial prioritization of multiple agents studied concurrently or for dosage-range evaluations, it has not gained wide usage in a commercial setting. As proposed, use of the Chernoff-Kavlock assay in an industrial setting is relatively inefficient, in terms of animal usage and data produced, when compared with available alternative study designs. Only a single dosage level was studied, and the data obtained from the assay do not provide sufficient information to meet the minimum requirements of safety evaluations submitted for regulatory review. For these reasons, other methods of prioritization are generally used. Alternate methods used for initial screening and prioritization at our laboratory are: 1) the hydra developmental toxicity assay; and 2) a dosage-range study in rats. When the results of several pilot and definitive developmental toxicity assays performed in rats were compared, it appeared that the described pilot study served the dual functions of predicting and prioritizing the developmental hazard of the test agent and providing a dosage-range study that identified the appropriate dosages to be tested in the definitive study. PMID- 2884745 TI - Further evaluation of an in vivo teratology screen. AB - The in vivo teratology screening procedure described previously [Chernoff N, Kavlock RJ: J Toxical Environ Health 10:541-550, 1982] was further evaluated using a total of 46 chemicals in 50 different treatment regimens. Pregnant CD-1 mice were generally treated by oral gavage on days 8-12 of gestation at a dose level predicted from a preliminary range finding study to induce a slight degree of maternal toxicity. The effects on early postnatal growth and viability were compared to results generated from standard mouse teratology bioassays as reported in the literature (there were nine regimens for which no valid comparisons could be made). The procedure correctly categorized 25 of the 30 treatment regimens which were considered developmentally toxic in the mouse, as well as nine of 11 which were considered to be nondevelopmentally toxic in the mouse. Thus, based upon the criteria used in the present study, the assay correctly classified 83% of the chemicals tested as to their effect in a standard mouse bioassay. The five nonconcurring negative findings were likely due to a combination of pharmacokinetic differences between the studies, as well as to the cessation of dosing on day 12, while critical events of organogenesis are still occurring. The assay achieves the requirements for a teratology screening system, but improved predictability would result from the addition of a lower dose level and extension of the dosing period to include later stages of organogenesis. PMID- 2884746 TI - The Chernoff-Kavlock assay: its validation and application in rats. AB - As the rat is the preferred species for teratogenicity studies in our laboratories, the Chernoff-Kavlock assay was modified and validated for use in this species. The Alpk:AP (Wistar-derived) strain, which is also used routinely for toxicology studies, was used, under standard SPF conditions. Twenty-six chemicals have been assayed to demonstrate the utility of the system as a predictor of rat teratogens and to develop a set of rules for interpretation of the results. Routes of chemical administration were largely gavage, with some dermal, subcutaneous, inhalation, and intraperitoneal applications. The use of the assay in five modes to assist the toxicological evaluation or understanding of chemicals is displayed. These modes are 1) as a pre-screen, 2) to compare analogues/homologues, 3) to provide a rapid hazard estimate, 4) to generate a dose-response, and 5) to test a hypothesis. PMID- 2884747 TI - A recommended protocol for the Chernoff/Kavlock preliminary developmental toxicity test and a proposed method for assigning priority scores based on results of that test. AB - Recommendations are made for a standard protocol for the Chernoff/Kavlock preliminary developmental toxicity test, and a weighted scoring system is proposed to provide a numerical prioritization. Protocol recommendations include use of pregnant animals for dose-finding studies and, in the testing phase, treatment on gestation days 6-15 at an overtly maternally toxic dose. This treatment period corresponds to the usual timing of a teratology test and provides an improved data base in the event a conventional test is deemed appropriate. Five indices of potential developmental toxicity are: the proportion of pregnant survivors at term that produces a viable litter (at least one liveborn pup), average litter size and pup weight at birth, and average neonatal survival and body weight gain to 3 days of age. Neither systematic examinations of pups (living or dead) for malformations nor counts of dead pups are considered productive. In the proposed method for point scores, each of the five indices is assigned a point value that varies according to broad classes of maternal toxicity. The maximum total point value is 22. When there is no statistically significant difference between treated and control groups, the assigned value is subtracted from 22. If there is a statistically significant treatment effect, or if statistics cannot be applied, then no points are subtracted. The points remaining after all five indices are considered constitute the priority score, which may range from 0 (low) to 22 (high priority). PMID- 2884748 TI - An indirect assessment of the Chernoff/Kavlock assay. AB - The underlying principle of the Chernoff/Kavlock assay--namely that prenatal toxicity can be detected by means of simple postnatal endpoints--is strongly supported by experience gained in performing reproductive and developmental toxicity studies to international requirements. Compared with the supposedly more sophisticated procedures of regulatory tests, the simpler endpoints of the assay offer greater speed, economy, consistency and reliability. At the most, there is only a marginal loss of sensitivity in respect of detecting the lowest dosage at which effects may occur. The assay is best used as a concept rather than as a protocol with, "tailored" variations providing effective means of priority selection from a series of chemicals, especially analogue series. The underlying principle is applicable at levels through and beyond formal regulatory testing. PMID- 2884749 TI - [Neuroleptics and akathisia]. PMID- 2884750 TI - [Pharmacokinetic interaction between clomipramine and phenothiazines]. PMID- 2884751 TI - [Psychopharmaca and the elderly]. PMID- 2884752 TI - [Prenatal diagnosis of cystic fibrosis]. AB - A review is presented of prenatal diagnosis of cystic fibrosis (CF). Two approaches are presently available: DNA-probing in chorionic villi (8th-10th week of gestation) and determination of microvillar enzymes in amniotic fluid (17th or 18th week of gestation). DNA-probing makes use of linked markers (restriction fragment length polymorphisms). This means that prenatal diagnosis is only possible when DNA of an earlier affected sib is available. Moreover the parents have to be informative with respect to the DNA-markers. This is the case in the majority of families, but not in all of them. Also the possibility of recombination has to be taken into account. For that reason families should preferably be referred before pregnancy. In the majority of cases presence or absence of CF in the fetus can be determined with high probability. A hundred percent certainty however is not possible with present techniques. Determination of microvillar enzymes in amniotic fluid is based on the fact that the concentration of these enzymes in general is lower in CF fetusses than in normal ones. There are however overlapping values. So, also with this technique, a hundred percent certainty is impossible. This type of prenatal diagnosis is especially suitable in families in which DNA-probing is impossible or gives insufficient discrimination between affected and unaffected fetusses. Looking for a meconium accumulation by means of ultrasound can support diagnosis. PMID- 2884753 TI - Lack of linkage between HLA and multiple endocrine neoplasia type 2 in a French family. AB - In this study, linkage between HLA and a dominant gene determining multiple endocrine neoplasia type 2 (MEN 2) in a large pedigree was investigated. All lod scores for recombination fractions ranging from 0 to 0.45 were negative. If we pool data from our family and the families studied by Jackson et al. (1976) and Simpson & Falk (1982), a link between HLA and the locus for MEN 2 can be excluded. Linkage studies with various markers and pooled data should be pursued to permit detection of high risk individuals and to identify a genetic defect. PMID- 2884754 TI - [Clinical testing of a dry chemistry working laboratory apparatus, the "Reflotron"]. AB - The veterinary range of application of the laboratory unit "Reflotron" (Boehringer Mannheim) was tested. This laboratory unit is able to measure the parameters glucose, urea, hemoglobin, GGT, cholesterol, triglyceride and in forthcoming future uric acid, AST, ALT and creatinine out of whole blood. It is easy to operate this apparatus. The "Reflotron" gives reliable results. PMID- 2884756 TI - The inactivation of Clostridium perfringens epsilon toxin by treatment with tetranitromethane and N-acetylimidazole. AB - When one residue of tyrosine per molecule of epsilon toxin was nitrated by tetranitromethane, the modified toxin lost more than 90% of its original activity. The toxin also was inactivated by treatment with N-acetylimidazole. The lethality was restored when the inactive N-acetylimidazole-treated toxin was treated with hydroxylamine. The inactive N-acetylimidazole-treated toxin was not nitrated by tetranitromethane under conditions where one residue of Tyr per molecule of the untreated toxin is nitrated. These data suggest that only one Tyr residue in the toxin is important for the lethal activity. PMID- 2884755 TI - Embryotoxicity elicited by inhibition of gamma-glutamyltransferase by Acivicin and transferase antibodies in cultured rat embryos. AB - Acivicin (also known as AT-125) and IgG isolated from goat anti-gamma glutamyltransferase antiserum were used to inhibit the activity of gamma glutamyltransferase (GGT, EC 2.3.2.2) in rat conceptuses cultured from Days 10 to 11 of gestation. Inhibition of GGT by either Acivicin or anti-GGT IgG produced embryotoxicity and malformations, although each compound produced a unique spectrum of effects. Acivicin, at an initial concentration in the culture medium of 5 microM, produced a marked decrease in yolk sac vasculature and was associated with embryonic malformations such as neural tube necrosis, microophthalmia, and cephalic edema after 24 hr exposure. These malformations were accompanied by significant decreases in both embryonic and yolk sac protein, yolk sac GGT activity, as well as embryonic glutathione (GSH) levels. In contrast, anti-GGT IgG produced no apparent effects on yolk sac vasculature or protein after exposure of conceptuses to an initial concentration of 50 micrograms IgG/ml culture medium, even though equal inhibition of yolk sac GGT (30%) was achieved by each inhibitor. Exposure to IgG (50 micrograms/ml) for 24 hr was associated with decreased embryonic protein; decreased levels of GSH in the embryo were observed after both 3 and 24 hr. The dichotomy of effects on the yolk sac by the two compounds indicates that Acivicin produced these effects by mechanisms other than by GGT inhibition alone. These results demonstrate that inhibition of GGT in rat embryos undergoing organogenesis can elicit embryotoxic effects and produce alterations in GSH levels. The capacity of the anti-GGT antibody to inhibit the GGT activity in the yolk sac (while having no apparent effect on yolk sac morphology), and yet influence the embryo by decreasing protein and GSH levels, underscores the important role of the yolk sac during the highly sensitive stages of organogenesis. PMID- 2884757 TI - Effect of testosterone on the testicular atrophy caused by di(2 ethylhexyl)phthalate (DEHP). AB - The involvement of testosterone in di(2-ethylhexyl)phthalate (DEHP) induced testicular injury has been examined by coadministration of testosterone (1 mg/kg) along with DEHP (2000 mg/kg) daily for 15 days. The coadministration of testosterone and DEHP appears to have prevented the testicular injury as judged by the biochemical and histopathological changes. The sperm count and the activity of the testicular enzymes, gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), sorbitol dehydrogenase (SDH), beta-glucuronidase and acid phosphatase, related with the maturation of sperm, which were significantly altered by DEHP treatment were found to be within normal levels after the combination treatment of DEHP and testosterone. The histopathological studies also showed more or less normal spermatogenic events. The results of this study have suggested the involvement of testosterone in DEHP induced testicular atrophy. PMID- 2884758 TI - Renal blood flow in acute cerebral ischemia in spontaneously hypertensive rats: effects of alpha- and beta-adrenergic blockade. AB - The influences of acute cerebral ischemia on renal hemodynamics were examined in spontaneously hypertensive rats in which cerebral ischemia was induced by bilateral carotid artery occlusion. Renal and cerebral blood flow were measured with a hydrogen clearance technique. Either phenoxybenzamine (0.5 mg/kg body wt) or propranolol (2 mg/kg) was given i.v. immediately after ischemia was induced to examine the drugs' effects on cerebral and renal hemodynamics. One hour after ischemia, cerebral blood flow was markedly reduced to 5, 3, and almost 0% of the preischemic value in the untreated, phenoxybenzamine-treated, and propranolol treated rats, respectively. In contrast, renal blood flow at that time was decreased to 65, 88, and 67%, respectively. The calculated renal vascular resistance was similarly increased to 151% in the untreated and 136% in the propranolol-treated rats, but decreased to 82% in the phenoxybenzamine-treated rats. The present results indicate that in acute cerebral ischemia renal blood flow was considerably decreased with concomitant increased renal vascular resistance, and that such reduction in renal blood flow was minimized by alpha adrenergic blockade but not by beta-blockade. It is concluded that activation of the alpha-adrenergic system in acute cerebral ischemia causes renal vasoconstriction. PMID- 2884759 TI - The Italian hemodilution trial in acute stroke. Italian Acute Stroke Study Group. AB - The Italian Acute Stroke Study is a prospective, multicenter, randomized, clinical trial to evaluate hemodilution in acute stroke. Thirty-one centers will recruit 1,200 patients with a recent (less than 12 hours) hemispheric acute stroke. Randomization is performed centrally, and patients are stratified by center and severity of neurologic deficit. Hemodilution is achieved by venesection and infusion of the same amount of dextran 40. Otherwise, both treated and control groups receive the standard treatment provided by each center within agreed guidelines. At 6 months after stroke, one member of the Clinical Coordinating Center, blind as to treatment allocation, collects data on mortality and disability by telephone. We expect to terminate the randomization on December 31, 1986, and the follow-up evaluation on June 30, 1987. The aim of the study is to evaluate whether mortality and disability are significantly reduced in the group treated with hemodilution compared with the control group. PMID- 2884760 TI - Regression of carotid stenoses after corticosteroid therapy in occlusive thromboaortopathy (Takayasu's disease). AB - A 34-year-old, single Japanese woman with active Takayasu's disease presented with stenosed bilateral common carotid arteries, subtotal occlusion of the left subclavian artery, and complete occlusion of the ipsilateral proximal vertebral artery, as demonstrated by angiography. A right subclavian-left vertebral bypass using an autologous saphenous vein graft was successfully performed after 36 days of corticosteroid therapy. Subsequently, warfarin was administered in addition to prednisolone. After 32 months of treatment with a gradual reduction from 50 to 3.75 mg of prednisolone daily, angiography revealed a functioning bypass graft and regression of bilateral common carotid stenoses. PMID- 2884761 TI - The major histocompatibility complex of the rat. AB - Immunogenetic studies in the rat began with the investigation of blood group antigens (1-7) and evolved into the investigation of histocompatibility antigens and transplantation phenomena (8-17). In the course of this work, several nomenclature systems evolved that were eventually reconciled in a series of comparison studies (18-24). The biennial Workshops on Alloantigenic Systems in the Rat held under the aegis of the Transplantation Society (24) have provided the forum for the continued evolution of this field. In addition, several reviews (24-31) and books (32-35) have provided periodic summaries of different aspects of rat immunogenetics. This review will focus on the structure of the major histocompatibility complex (MHC) of the rat from the serological, biochemical, and molecular points of view. PMID- 2884762 TI - Identification of the IA hybrid molecule affecting anti-Thy-1 responsiveness. PMID- 2884763 TI - [Genetic transformation of somatic cells. XII. Mutations in human satellite DNA introduced into Chinese hamster cells]. AB - Data are presented about detailed restriction mapping, hybridization and sequence analysis of plasmid pRT301 rescued into E. coli 25-30 cell divisions after transfection of Chinese hamster cells. This plasmid contains an insert of human satellite III fragment (HS3), which was replicated many times in mammalian cells, and we found multiple point mutations in this non-selectable fragment, mainly single inserts of GC base pair. Specificity of mutagenesis of HS3 induced by transfection and replication in Chinese hamster cells differs from mutagenesis specificity found by other authors for selectable genes. PMID- 2884764 TI - The effect of cysteamine on the somatostatin content of guinea-pig islets. AB - Cysteamine is known to deplete the immunoreactive somatostatin content in different organs from rat and mouse. The aim of the present work was to test if cysteamine also affects the somatostatin content in guinea-pig islets, since guinea-pigs have a carbohydrate metabolism different from that of other laboratory animals. Cysteamine was injected to guinea-pigs and the pancreatic islets were isolated four hours later. Cysteamine was also incubated in vitro with isolated pancreatic islets from untreated guinea-pigs. Cysteamine depleted the somatostatin content in the pancreatic islets in both the in vivo and in vitro studies. PMID- 2884765 TI - Cytogenetic analysis of men with cryptorchidism and reduced fertility. AB - A cytogenetic chromosomal analysis was performed in 140 infertile men with cryptorchidism--85 with unilateral and 55 with bilateral. The most frequent anomaly was sex chromosomal aneuploidy found in 7.1% of patients. This is significantly higher compared to a group of infertile men with normal descended testes. Other chromosomal anomalies were not more frequent than in infertile men without cryptorchidism. PMID- 2884766 TI - [Regional microcirculatory disorders in peritonitis]. AB - Investigations performed under experimental and clinical conditions have shown that regional microcirculatory alterations in peritonitis consist in the arterial spasm, arteriovenous shunt of blood, hypoperfusion of the intestine, local metabolic disorders. The application of alpha-adrenoblockaders is recommended for directed action on microcirculation with an obligatory correction of deficit of the circulating blood volume. PMID- 2884767 TI - In defence of gentamicin. PMID- 2884768 TI - Polymorphism of the acetylcholine receptor in the horse. AB - A cDNA probe to the alpha subunit of the murine acetylcholine receptor was used to demonstrate restriction fragment length polymorphism in an acetylcholine receptor gene in the horse. Three different patterns of polymorphism have been observed with fragment sizes of 4.3 and 2.9 kilobases (kb) (pattern 1), 4.3 and 2.5 kb (pattern 2) and 4.3, 2.9 and 2.5 kb (pattern 1,2). Analysis of a three generation pedigree has suggested that patterns 1 and 2 represent two allelic forms of the gene encoding the alpha subunit of the acetylcholine receptor. These data provide a basis for the examination of the genetic control of neuromuscular function in the horse. PMID- 2884769 TI - The effect of the host's age on the pathology of Eimeria stiedai infection in rabbits. AB - The pathology of experimental Eimeria stiedai infection in 2- and 4-month-old rabbits raised coccidia-free was studied. Over 50 days of infection, the serum activities of aspartate (AST) and alanine (ALT) aminotransferases, alkaline phosphatase (AP) and gamma-glutamyltranspeptidase (GGTP) were analyzed as indicators of hepatic lesions and total serum globulins with respect to the immune response of the host; parasite development was followed by oocyst output; weight gain, food intake and relative liver weight were analyzed to control the performance of infected animals. The age of the host strongly affected parasite development and consequently the biochemical and zootechnical parameters differed more markedly in the younger animals; however, the enzyme ALT showed an increase independent of parasite development, and infection did not affect GGTP activity. The increase in age was responsible for resistance of rabbits to hepatic coccidiosis and older animals were less affected than young ones. PMID- 2884770 TI - Immunohistochemically demonstrated increase in glutathione S-transferase species in propylnitrosamine-induced focal proliferative and neoplastic Syrian hamster pancreatic lesions. AB - Immunohistochemical investigation of focal proliferative and neoplastic Syrian hamster pancreatic lesions induced by propylnitrosamine administration revealed a distinct pattern of expression of different molecular forms of glutathione S transferase (GST) during neoplastic development. Initial increase in levels of GST placental (P) and B forms in early ductal/ductular proliferations and atypical (dysplastic) lesions was followed by a drop in the latter during transition to carcinoma. Unequivocal acinar cells observed within so-called 'pseudoductules' did not share the altered phenotype evident in ductular elements, suggesting their non-involvement in the generation of early lesions. However, the fact that component cells were occasionally of abnormal morphology did not allow the exclusion of acinar cell participation in histogenesis. Elevation of GST-A and C forms was limited to stromal elements surrounding the epithelial lesions and since they were associated with benign, cystic as well as atypical lesions and a similar increase was observed after common duct ligation, they appeared to be non-specific. The results indicated independent control of expression of individual GST forms and suggest that biochemical similarities exist between early, putative preneoplastic lesions induced by propylnitrosamines in the hamster lung, liver (both hepatocellular and intrahepatic bile duct) and pancreas. PMID- 2884771 TI - Effects of tumor necrosis factor (TNF) on transplanted tumors induced by methylcholanthrene in mice. A histopathologic study. AB - The effects of a highly purified tumor necrosis factor (TNF) on transplanted methylcholanthrene (Meth A)-induced murine tumors were compared with those of lipopolysaccharide (LPS). TNF caused immediate subepidermal edema and hyperemia followed 2 h later by fibrin thrombi in tumor blood vessels. Finally hemorrhagic necrosis with dispersal of tumor cells occurred. LPS produced similar hemorrhagic necrotizing changes. However, the necrotic action of LPS was delayed and complete tumor regression was not achieved with LPS. These findings suggest that tumor necrosis induced by TNF is due to circulatory disturbance associated with a microvascular injury in the tumor manifested by hyperemia and multiple fibrin thrombi. PMID- 2884772 TI - Changes in the acinar distribution of some enzymes involved in carbohydrate metabolism in rat liver parenchyma after experimentally induced cholestasis. AB - Extrahepatic cholestasis induced by ligation and transsection of the common bile duct caused a change in the parenchyma/stroma relationship in rat liver. Two weeks after ligation, the periportal zones of the parenchyma were progressively invaded by expanding bile ductules with surrounding connective tissue diverging from the portal areas. Parenchymal disarray developed and small clumps of hepatocytes or isolated hepatocytes were scattered within the expanded portal areas. These cells showed normal activity of lactate, succinate and glutamate dehydrogenase and may, therefore, be considered to be functionally active. After cholestasis the remainder of the liver parenchyma showed adaptational changes with respect to glucose homeostasis, as demonstrated by histochemical means. Glycogen stores disappeared completely whereas glycogen phosphorylase activity increased about ten fold. The increased glycogen phosphorylase activity and glycogen depletion indicate a greater glycogenolytic capacity in liver parenchyma after bile duct ligation to maintain as far as possible a normal plasma glucose concentration. The parenchymal distribution pattern of glucose-6-phosphatase activity did not change significantly after bile duct ligation. The isolated hepatocytes within the expanded portal tracts showed a high activity of this enzyme whereas the pericentral parenchyma was only moderately active. The distribution patterns of glucose-6-phosphate dehydrogenase and lactate dehydrogenase activity in the liver parenchyma were also largely unchanged after bile duct ligation, but the histochemical reaction for glucose-6-phosphate dehydrogenase activity demonstrated infiltration of the remainder of the parenchyma by non-parenchymal cells, possibly Kupffer cells and leucocytes as part of an inflammatory reaction. Under normal conditions the mitochondrial enzymes succinate and glutamate dehydrogenase show an opposite heterogenous distribution pattern in liver parenchyma. Following cholestasis both enzymes became uniformly distributed. The underlying regulatory mechanism for these different changes in distribution patterns of enzyme activities is not yet understood. PMID- 2884773 TI - The nature of host tissue destruction in tumor invasion. An experimental investigation on carcinoma and sarcoma xenotransplants. AB - The nature of host tissue destruction in tumor invasion was investigated in experimentally induced carcinomas and sarcomas, xenografted into skeletal muscle. By means of light and electron microscopy it was shown that in both carcinomas and sarcomas the confrontation of host tissue with the invading tumor cells does not result in immediate destruction of host tissue but in a transitory state of coexistence which gradually proceeds to progressive host tissue atrophy. This process of progressive atrophy, which finally results in the total disappearance of the invaded host tissue, is considered to be caused mainly by the increasing pressure and competitive withdrawal of oxygen and nutrients by the invading and proliferating tumor cells. Morphological changes suggesting an active enzymatic breakdown of host tissue cells by tumor cells were not observed during any stage of tumor invasion. PMID- 2884774 TI - Ultrastructural localization of mercury in adrenals from rats exposed to methyl mercury. AB - Accumulations of mercury have been demonstrated in adrenal glands by light and electron microscopy with a highly sensitive histochemical technique. Rats were exposed to methyl mercury in drinking water (20 mg/l) for 7-180 days, or were given intraperitoneal injections of methyl mercury (daily dose 100 or 200 micrograms). The amount and location of the mercury deposits were dependent upon the exposure time, the method of administration and the amount administered. In rats exposed to methyl mercury in drinking water, accumulations were often observed in both the zona glomerulosa and reticularis. They appeared first in the zona glomerulosa of animals treated for 1 week. In the zona fasciculata, deposits were observed only in the animals treated for 50 to 180 days. In animals treated for 180 days the cytoplasm of the cells in the zona fasciculata was heavily vacuolated and distinct necrotic cells were observed in other cortical zones. In the chromaffin cells, a slight increase in the amount of deposits was observed with increasing exposure time. Both epinephrenic and norepinephrenic cells contained deposits. Only a few deposits were observed in the cortical and chromaffin cells of animals treated with intraperitoneal injections. Ultrastructural deposits were observed in the lysosomes of cortical cells and in both lysosomes and secretory granules of chromaffin cells. PMID- 2884775 TI - Dissociation of Langerhans islets in the rabbit after pancreatic duct ligation. Immunocytochemical and ultrastructural studies. AB - In the rabbit, pancreatic duct ligation leads to serious disturbances of the pancreatic endocrine parenchyma. Immunocytochemical studies conducted over a short period (between 5 and 30 days post ligation) allow observation of a progressive dissociation of the Langerhans islets which initially affects the splenic part of the pancreas, a region where numerous large islets are found. This dissociation is followed by a dispersion of small heterologous endocrine cell clusters or isolated endocrine cells in a connective tissue which replace the exocrine parenchyma. On the 30th day after ligation ultrastructural studies show marked degranulation of the B cells demonstrating the great fragility of these cells. These observations of insular dissociation, scattering of the different endocrine cells and impairment of B cells are often reported in experimental and pathological studies of the pancreas. PMID- 2884776 TI - In vitro culture studies of granulocyte/macrophage and erythroid progenitor cells in lymphoproliferative disorders. AB - Granulocyte/macrophage progenitor cells (CFU-GM) and erythroid progenitor cells (BFU-E) have been assayed in peripheral blood (PB) and/or bone marrow (BM) from 12 patients with acute lymphocytic leukemia (ALL), 16 patients with chronic lymphocytic leukemia (CLL) and 31 patients with various forms of non-Hodgkin lymphoma (NHL) without BM involvement. Progenitor cell growth in PB and BM from the NHL patients did not differ statistically from controls (p greater than 0.1). CFU-GM and BFU-E per ml PB were markedly increased in ALL and CLL patients (p less than 0.001) while CFU-GM and BFU-E per plated BM cells from these patients were severely depressed (p less than 0.001). Lymphoblasts from one ALL patient failed to inhibit CFU-GM and BFU-E-derived colony growth from control PB mononuclear cells. The high levels of circulating progenitor cells in ALL and CLL patients clearly distinguish them from other cytopenic hematological malignancies, in which decreased progenitor cell levels have been demonstrated previously (acute myeloid leukemia, hairy cell leukemia). The cause of this finding and its pathophysiological implication still remains to be established. PMID- 2884778 TI - Tumorigenic poxviruses: transcriptional mapping of the terminal inverted repeats of Shope fibroma virus. AB - A composite transcriptional map for the entire 12.4-kb terminal inverted repeat (TIR) region of the Shope fibroma virus (SFV) genome has been determined. Northern blotting and S1-nuclease mapping were used to determine the regions which are transcribed, their temporal relationships, as well as the transcriptional initiation sites. Sequences representing the entire TIR are transcribed into poly(A)+ mRNA at both early and late times in the infection. Fifteen transcriptional initiation sites were mapped, 12 within the TIRs and 3 within the unique sequences close to the junction between the right TIR and the unique internal sequences. Ten of the 12 transcriptional initiation sites within the TIR and 2 of the 3 sites outside the right TIR correspond to the 5'-ends of the major open reading frames (ORFs) T1 to T9 plus the SFV growth factor gene. The 3 other initiation sites map within ORFs but near potential start codons for shorter polypeptides. All the expressed ORFs are tandemly arranged and transcribed toward the hairpin terminus. At early times during SFV infection of cultured rabbit cells, transcription of each ORF gives rise to a transcript of distinct size, while at late times termination of transcription is imprecise and substantial read-through into downstream sequences occurs. These results are discussed in light of recent observations on the related recombinant leporipoxvirus, malignant rabbit fibroma virus, which suggest that one or more gene products from this region of the SFV genome are implicated in viral tumorigenicity. PMID- 2884777 TI - Structure and origins of the HZ2-feline sarcoma virus. AB - The HZ2-feline sarcoma virus (HZ2-FeSV) is a replication-defective acute transforming feline retrovirus with oncogene homology to Abelson murine leukemia virus (A-MuLV) (P. Besmer, W.D. Hardy,Jr., E. E. Zuckerman, P. J. Bergold, L. Lederman, and H. W. Snyder, Jr. (1983) Nature (London) 303, 825-828). In contrast to A-MuLV which was isolated from a hematopoietic tumor, the HZ2-FeSV derives from a multicentric fibrosarcoma. We have molecularly cloned the HZ2-FeSV provirus from mink HZ2-FeSV nonproducer cells. The molecularly cloned HZ2-FeSV provirus is biologically active upon transfection of NIH 3T3 indicator cells. The genetic structure of the HZ2-FeSV provirus was determined by EM heteroduplex and Southern blot analysis. The HZ2-FeSV has a 6.8 kb-viral genome with the structure: 5' delta gag-abl-delta pol-delta env 3'. The abl insert, which is 1.4 kb, is located 1.9 kb from the 5' end and 3.5 kb from the 3' end of the viral genome. The 5' 1.9 kb in the HZ2-FeSV are colinear with 5' FeLV sequences, and the 3' 3.5 kb are colinear with 3' FeLV sequences, with the exception of a 0.85 kb deletion in the env gene. HZ2-FeSV v-abl and A-MuLV v-abl share 1.2 kb of abl sequences which are known to specify the protein kinase domain of the abl gene product and are necessary for fibroblast transformation in vitro. The DNA from several tumor tissues of cat 3590 from which the HZ2-FeSV was obtained was found to contain several HZ2-FeSV-related proviruses including the HZ2-FeSV. The variant HZ2-FeSVs have indistinguishable 5' gag-abl sequences; however, they differ in 3' sequences which likely do not include any abl sequences. The DNAs from fibrosarcomas obtained by inoculation of kittens with tumor extract were found to contain variant HZ2-FeSV proviruses as well. Taken together these results indicate a role for the HZ2-FeSVs in sarcomagenesis. PMID- 2884779 TI - [Changes in neurohumoral factors of various tissues in patients with breast cancer]. AB - Such neurohumoral factors of antitumor resistance regulation as catecholamines, corticosteroids and cholinergic mechanisms were studied in tissues of breast cancer patients. Tissue adjacent to tumor revealed elevated concentrations of 11 hydroxycorticosteroids and adrenaline matched by an increased release of norepinephrine which greatly depended on weakened cholinergic influences. These disturbances were pronounced in stages I and II tumors and, particularly, in infiltrating scirrhous cancer. Disbalance in neurohumoral factor distribution between normal and altered tissues may boost tumor recurrence and metastatic spread. PMID- 2884780 TI - [Features of inter-organ glutathione metabolism in rats provided with different amounts of protein and methionine]. AB - The total glutathione content was studied in the liver, kidneys and erythrocytes of rats given semisynthetic rations containing protein with 5, 10 and 15% of calorific value, as well as protein with 18% of calorific value supplemented with 0.125-0.425% of L-methionine. The total glutathione content in the liver directly depended on the protein content in the ration, while that in the kidneys did not vary with the protein level. The glutathione concentration in erythrocytes was significantly reduced with the rise of the protein quota in the ration. The addition of L-methionine to the ration also produced a reverse effect on the glutathione content in the liver and erythrocytes. However, the growth of the glutathione concentration in the liver and its lowering in the erythrocytes were recorded only after the addition of 0.125 and 0.225% of methionine. The rise of the methionine added up to 0.325 and 0.425% produced no effect on the glutathione concentration in the liver and erythrocytes, at the same time the glutathione concentration and gamma-glutamyltranspeptidase activity in the kidneys rose. It has been concluded that the methionine level in the ration, at which the glutathione content in the liver and erythrocytes is stabilized, can serve as a criterion of an adequately balanced ration for animals (with respect to methionine) with the use of casein as a protein source. PMID- 2884782 TI - [Gamma-glutamyl transpeptidase activity in the venous blood of the extremities in patients with stroke during exercise therapy]. PMID- 2884781 TI - A practical approach to improving pain control in cancer patients. AB - Despite a wealth of recent articles, many patients with cancer pain continue to suffer needlessly. The satisfactory treatment of cancer pain requires a variety of practical management strategies. Practicing physicians need a wider understanding of both the basic principles of analgesic therapy and the pharmacologic features of analgesics. Certain analgesics are best not used in cancer care. The use of pharmacologic adjuncts may lessen overall narcotic requirements and side effects. The appropriate use of alternative therapies can dramatically improve the quality of patients' overall survival. PMID- 2884783 TI - [Neuropathologic principles of senile dementia]. AB - Several groups of senile dementias with differing causes and neurohistological substrates can be distinguished. Genetically determined Pick's disease produces severe neuronal atrophy; Alzheimer's disease is characterized by pathological neurofibrillary changes. Jakob-Creutzfeldt disease and Gerstmann-Straussler Scheinker disease are slow virus diseases induced by unconventional agents. These diseases, after an incubation time of several years, take the course of slowly progressive degenerative diseases of the central nervous system without inflammatory and specific immune reactions of the host organism. Regarding pathogenesis these diseases were interpreted as degenerative processes as long as their transmissibility was yet unknown. The fact that so-called slow virus diseases can also produce argyrophilic plaques is a further common feature of this group of diseases and human pathological aging processes. So far, however, there is no proof that Alzheimer's disease is caused by an unconventional agent. On the other hand, common features of the products of aging changes and of unconventional viral diseases are apparent. In this paper current knowledge of pathogenetic mechanisms in this rapidly developing field of research is presented. Some relevant factors of organic dementia are discussed: special characteristics of neuronal atrophy (functional role of dendrites); architectonics of cerebral atrophy (laminar versus modular atrophy); neurotransmitter changes (causes or sequels of dementia) and a possibly non specific origin of senile plaques. Finally, the clinical relevance of neurobiological research into dementias is emphasized. PMID- 2884785 TI - [Gas gangrene]. PMID- 2884784 TI - Serum gastrin, calcitonin, and prolactin as markers of multiple endocrine neoplasia syndromes in patients with primary hyperparathyroidism. PMID- 2884786 TI - E-type prostaglandin binding sites in isolated canine parietal cells: elucidation with (3H) misoprostol free acid. AB - (3H) Misoprostol free acid, a prostaglandin E1 analog, was used to identify high affinity binding sites for E-type prostaglandins in enriched canine parietal cell preparations. Saturable, reversible, and highly stereospecific binding, with an estimated number of 8000 binding sites per cell, was demonstrated. The binding sites have high affinity for misoprostol, misoprostol free acid, and other E-type prostaglandins. Prostaglandins of the I- and F-type bind weakly, and chemically unrelated compounds, such as histamine and cimetidine, do not bind. The results indicate that (3H) misoprostol free acid binds to E-type prostaglandin receptors, and that the ulcer-healing drug, misoprostol, inhibits gastric acid secretion through interaction with a specific E-type prostaglandin receptor. PMID- 2884787 TI - [Anatomical bases of the neural regulation of the gastrointestinal organs]. AB - The nervous regulation of splanchnic organs is based on a hierarchic morphological system including the central and peripheral nervous system. The efferent nerves of the viscera stem from the medullo-spinal primary centers which are superordinate to the intrinsic nerve plexus of the splanchnic organs. The medullo-spinal activity is modulated by specific and unspecific higher centers (nuclei) of the entire brainstem. The afferent nerves of the viscera reach the medullo-spinal centers via sympathetic pathways and the dorsal root ganglia as well as via the medulla oblongata via the vagus nerve and the nodose ganglion. These primary sensory neurons end at various centers of the medullo-spinal system. That is, they are connected to the primary centers. The afferent nerves guarantee direct control over the functional status of the viscera. The neurotransmitters of the entire autonomic circuits are specific to the splanchnic organs. Catecholaminergic, acetylcholinergic, and GABA-ergic neurons contain a variable pattern of co-stored neuropeptides which are responsible for the individual properties of the circuits of each visceral organ. PMID- 2884789 TI - The ependyma of sheep. III. The third cerebral ventricle. PMID- 2884788 TI - [Therapy of urticaria with H1 and H2 antihistaminics. Results of clinical and experimental studies]. AB - The antipruritic effect of modern H1- and H2-receptor blockers in chronic urticaria, that had been clinically proved, was experimentally studied by means of the histamine weal test. The H2-antihistamine preparation ranidine alone did not clearly reduce weals or erythemas induced by histamine when compared with a placebo. As expected, both parameters were markedly reduced by the H1 antihistamine preparation terfenadine. After combined administration of both drugs, the effect of the H1-blocker proved to be significantly increased. We discuss the possible mode of action and the consequences for anti-allergic therapy. PMID- 2884790 TI - Bioindication in coral reef ecosystems. AB - The concept of bioindication in the sense of the use of organisms for detecting environmental stress has been employed in coral reef conservation and management for the past several years. Important tools are coral growth rates and various community parameters, notably hard coral cover. The present need is the optimal coordination of international efforts for the earliest possible institution of an effective monitoring system. PMID- 2884791 TI - Drugs recently released in Belgium. Recombinant methionyl human growth hormone, synthetic growth hormone-releasing factor, somatostatin. PMID- 2884792 TI - Glucose, beta adrenergic effects, and pancreatic endocrine function in the isolated perfused duck pancreas. AB - Duck isolated perfused pancreas was used to assess glucose, adrenergic mediated effects and pancreatic function interrelationships. A moderate physiological 50% increase in glucose level, corresponding closely to the difference observed between 24-h-fasted and fed animals, induced a significant decrease of pancreatic glucagon not due to a rise in somatostatin secretion. The great responsiveness of the A cell was still found after glucagon stimulation by catecholamines or beta adrenergic agonism. Insulin was irresponsive to the glucose load we used, suggesting that glucose-induced glucagon suppression was also insulin independent. As far as the D cell was concerned, glucose had no effect on pancreatic somatostatin output; however, an interesting finding was that beta adrenergic agonism has a permissive effect on D cell responsiveness to the nutriment. PMID- 2884793 TI - Neuropeptide Y directly inhibits growth hormone secretion by human pituitary somatotropic tumours. AB - Neuropeptide Y (NPY) is a 36 amino acid peptide, widely distributed throughout the brain and is found in hypothalamic neurones. This latter finding suggests that NPY may possess a hypophysiotropic function. A number of studies have demonstrated effects of NPY on LH and GH secretion by rat pituitary cells. We report here the results of experiments investigating the effects of NPY on GH secretion by tumorous human somatotropic pituitary cells in culture. NPY (0.25-25 nmol/l) inhibited GH secretion by 20-53%, the maximal effect depending upon the tumour studied. The potency of NPY was less than that of somatostatin (SRIH). The stimulatory effects of growth hormone releasing factor (GHRH) and theophylline were reduced by NPY, but NPY did not modify the inhibitory effect of SRIH on GH secretion. It is concluded that NPY may be involved in the control of GH secretion, at least by tumorous human pituitary somatotropes. PMID- 2884794 TI - A sensitive and practical assay for thyroid-stimulating antibodies using FRTL-5 thyroid cells. AB - A sensitive, precise and practical assay for thyroid stimulating antibodies was developed in which poorly differentiated rat thyroid cells (FRTL-5) were exposed to crude immunoglobulin fractions precipitated from serum with 15% polyethylene glycol under hypotonic conditions. After the incubation at 37 degrees C for 2 h, cAMP released into Hank's medium without NaCl was determined by radioimmunoassay. The removal of NaCl from the isotonic Hank's medium greatly enhanced cAMP production in response to both TSH and thyroid stimulating antibodies. The assay was sensitive enough to elicit an approximately 30-fold increase in cAMP at 10 mU/l bovine TSH. Thyroid stimulating activities measured using FRTL-5 cells significantly correlated with those measured using cultured porcine (r = 0.918, N = 72) or human (r = 0.830, N = 23) thyroid cells. Thyroid stimulating activities were detected in all of the 50 patients with hyperthyroid Graves' disease, the 14 patients with recurrent hyperthyroid Graves' disease, and the 25 patients with ophthalmic Graves' disease. Thyroid stimulating activity was also detected in some patients (9/24, 37.5%) with Hashimoto's thyroiditis whose serum TSH concentrations were higher than 30 mU/l. However, it was completely abolished by pre-treatment of the sera with anti-TSH antibodies. Although thyroid stimulating activities were detected in one of the patients with simple goitre (N = 10) and in one with thyroid cancer (N = 10), none of the patients with silent thyroiditis (N = 7), adenomatous goitre (N = 11), and thyroid adenoma (N = 9) were positive for thyroid stimulating antibodies. PMID- 2884795 TI - Elevated anti-alpha-galactosyl antibody titres. A marker of progression in autoimmune thyroid disorders and in endocrine ophthalmopathy? AB - The titres of anti-alpha-galactosyl antibodies were measured by passive haemagglutination in 50 control subjects and in 128 patients presenting with various thyroid disorders. Titres of control subjects ranged from 1/10 to 1/80, regardless of age and blood group. Elevated titres (greater than 1/80) were constantly noted in 6/6 patients with progressive exophthalmos, in 5/5 patients with untreated Graves' disease, and in 11/12 patients with progressive nontoxic goitre. By contrast, the titres were within the normal range in primary myxoedema (17 patients) and in residual exophthalmos (11 patients), whereas they were only erratically increased in 1/31 patients with treated or cured Graves' disease and in 5/36 patients with nonprogressive nontoxic goitre. Finally, elevated titres were also found in 3/7 patients presenting with autoimmune thyroiditis. No correlations could be established between elevated titres and the thyrotropin binding inhibiting immunoglobulin activity, the antithyroglobulin antibody titres or the antimicrosomal antibody titres. As in the control subjects, the anti-alpha galactosyl antibodies mainly belonged to the IgG class. Affinity purified anti alpha-galactosyl antibodies were capable of binding to trypsinized human and porcine thyroid cells in culture, as shown by indirect immunofluorescence. On the other hand, they were not able to react with untreated thyroid cells. The data show that the measurement of anti-alpha-galactosyl antibody titres could represent an easy and useful tool to determine whether an autoimmune thyroid disorder is in progression. Besides, they suggest that some of the antigenic determinants implicated in the enhanced production of anti-alpha-galactosyl antibodies are present, but normally hidden, within the cell surface of thyroid cells. PMID- 2884796 TI - Comparison of atracurium, pipecuronium, and vecuronium for tracheal intubation. AB - In order to compare tracheal intubation conditions, 34 adult patients about to undergo elective surgery received at random atracurium 0.5 mg X kg-1, pipecuronium 0.1 mg X kg-1 or vecuronium 0.1 mg X kg-1, intravenously. Intubation was attempted when only the first of the train-of-four finger contractions, arising from ulnar nerve stimulation, remained. The three relaxants provided effective conditions for intubation. The time required to suppress all but the first train-of-four response was shortest in the group given atracurium (P less than 0.05). Compound muscle action potentials (emg) were continuously filmed from just before induction of anesthesia until the trachea was intubated. The degree of neuromuscular blockade was similar in the three study groups. PMID- 2884797 TI - Priming with vecuronium and atracurium--a comparison. AB - Vecuronium (V) and atracurium (A) were compared in a randomised study in premedicated patients undergoing laparoscopy for gynecological pathology. Both groups contained ten patients. Anesthesia was induced with fentanyl (0.1 mg) and thiopentone (1 mg/kg initially and subsequently 4 mg/kg). A priming dose of vecuronium (20 micrograms/kg) or atracurium (100 micrograms/kg) was given one minute before the intubating dose (60 micrograms/kg for vecuronium and 300 micrograms/kg for atracurium). Ninety seconds thereafter intubation was performed. Maintenance of anesthesia consisted of isoflurane at an inspiratory concentration of 1% in a mixture of O2/N2O (50%/50%) with small supplements of fentanyl. Neuromuscular block was monitored with the Datex Relaxograph. Results show that neither drug offers major clinical advantages over the other: there is no difference in speed of onset (V:T190sec 14.6 +/- 4.3%; A:T190sec 23.5 +/- 6.5%; Mean +/- SEM) and duration of neuromuscular block (V:T150sec 34.2 +/- 3.5 min; A:T150sec 41.3 +/- 2.8 min; Mean +/- SEM) and intubation conditions are almost identical. PMID- 2884798 TI - Serum antibodies to HTLV-I in human demyelinating disease. AB - Serum HTLV-I antibodies were measured in 17 MS patients and 2 closely matched control groups by 2 different independent assays. A highly sensitive particle agglutination test was used to detect HTLV-I core protein antigens and an immunoblot assay with E. coli-expressed P21E transmembrane protein was employed to detect antibodies to HTLV-I evelope antigens. No serologic evidence of prior HTLV-I infection in our population of multiple sclerosis (MS) or Guillain-Barre Syndrome (GBS) patients was found. PMID- 2884799 TI - Clinical experience with GRF. AB - Growth hormone releasing factor (GRF) is one of two main releasing hormones which control pituitary hGH production and release. This activity is retained even when the length of the GRF polypeptide is reduced to the 29 N-terminal residues. This 29-residue polypeptide has been chemically synthesized, and testing in healthy volunteers elicited secretion of hGH to a maximum level of about 40 ng/ml. In a trial of children with various disorders, the maximum hGH response was reached within 60 minutes; those children with hGH deficiency showed much lower responses than those with other disorders not related to hGH deficiency. The frequency of false-positive tests was low, and it is proposed that GRF testing could provide a useful additional tool in the diagnosis of hGH deficiency. PMID- 2884800 TI - [Effect of higenamine on alpha-adrenoceptors]. PMID- 2884801 TI - [Effects of 4 psychotropic drugs and 4 central neurotransmitters on lipid peroxidation in the human erythrocyte membrane]. PMID- 2884802 TI - [Alpha-adrenoceptor blocking effect of berberine in isolated rat anococcygeus muscles and rabbit aorta strips]. PMID- 2884803 TI - C-terminal fragments of oxytocin (prolyl-leucyl-glycinamide and Z-prolyl-D leucine) attenuate the development of tolerance to ethanol. AB - Earlier it was found that oxytocin (OXT) treatment inhibited the development of tolerance to ethanol. In the present study the possibility was investigated whether the effect of OXT on ethanol tolerance was related to peptide fragments derived from the C-terminal part of the molecule. The actions of different doses of the C-terminal tripeptide (prolyl-leucyl-glycinamide, PLG) and of a synthetic dipeptide derivative (Z-prolyl-D-leucine, Z-Pro-D-Leu) on the development of tolerance to the hypothermic effect of ethanol in CFLP mice were therefore investigated. Peptide treatment did not affect body temperature in ethanol-naive animals. The acute effects (hypothermia, sleeping time) of a single ethanol injection were also unaffected by these peptides. In contrast, both PLG and Z-Pro D-Leu inhibited the development of tolerance to the hypothermic effect of ethanol. Accordingly, it might be speculated that a sequence active in affecting ethanol tolerance is located in the C-terminal part of the OXT molecule. PMID- 2884804 TI - Prejunctional adrenergic receptors and sympathetic neurotransmission: studies in canine skeletal muscle vasculature in situ. AB - The effects of sympathetic nerve stimulation were studied in blood perfused canine skeletal muscle in situ. The overflow of NA and vasoconstriction, which represent pre- and postjunctional events in this vascular bed, were frequency dependent and closely related to each other. Measurements of endogenous NA overflow were compared with a conventional radio-labelling technique using 3H-NA. Nerve stimulation evoked overflow of total radioactivity was recovered almost exclusively as 3H-NA. The relative changes of the nerve stimulation evoked overflow of endogenous NA and 3H-NA were much the same. The reproducibility was better for endogenous NA measurements than for the other two indices of transmitter release. Thus, endogenous NA overflow seems to provide a better measure of NA release. There was a preferential overflow of the newly stored radio-labelled transmitter, in agreement with earlier observations in vitro, showing that there is more than one compartment for NA storage in sympathetic nerve endings. Inhibition of neuronal uptake enhanced the nerve stimulation evoked overflow of NA and prolonged the vasoconstrictor response without influencing its amplitude. This would be consistent with a reduced clearance of the released transmitter without major alterations of the NA concentrations at the neuroeffector junction. Inhibition of prostaglandin synthesis did not influence nerve stimulation evoked NA overflow, suggesting that prostaglandin formation is of little importance for the modulation of NA release in this vascular bed. Postjunctional alpha-adrenoceptors of both subtypes may well contribute to the neurogenic control of vascular tone. Circulating catecholamines seem to be more important with regard to activation of the postjunctional alpha 2 adrenoceptors. Postjunctional beta 2-adrenoceptors are to all appearances activated principally by blood borne catecholamines. There was no evidence in favour of physiologically important neurogenic control of these receptors. Nerve stimulation evoked NA overflow was enhanced by alpha-adrenoceptor antagonists and reduced by alpha-adrenoceptor agonists. The findings lend further support to the suggested physiological role of prejunctional alpha 2-adrenoceptor mediated feed back inhibition of NA release. There may also be a subset of prejunctional alpha 1-adrenoceptors involved in the modulation of sympathetic neurotransmission. The existence of a prejunctional facilitatory beta 2-adrenoceptor could be demonstrated, as stimulation of beta 2-adrenoceptors enhanced nerve stimulation evoked NA overflow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884805 TI - Prejunctional beta 2-adrenoreceptor blockade reduces nerve stimulation evoked release of endogenous noradrenaline in skeletal muscle in situ. AB - Prejunctional beta-adrenoceptor-mediated modulation of endogenous noradrenaline (NA) overflow elicited by sympathetic nerve stimulation was studied in blood perfused canine gracilis muscle in situ. An attempt was made to subclassify these beta-adrenoceptors by comparing the effects of beta 1-selective (metoprolol) and non-selective (propranolol) beta-adrenoceptor blockade. Animals were pre-treated with desipramine and phenoxybenzamine in order to counteract possible influences of neuronal uptake and stimulation-evoked changes in vascular resistance on the diffusion of NA into the blood stream. Metoprolol did not decrease stimulation evoked NA overflow, as compared with control experiments (-10 and -8%, respectively). However, propranolol reduced stimulation-evoked NA overflow by 30% in metoprolol pre-treated animals (P less than 0.05 vs. control experiments). Both antagonists elevated basal perfusion pressure, suggesting that vascular post junctional beta 1- as well as beta 2-adrenoceptors are present. Propranolol increased stimulation-evoked vasoconstriction in metoprolol pre-treated animals, indicating that neuronally released NA may activate postjunctional beta 2 adrenoceptors under these experimental conditions. In conclusion, our findings suggest that NA release can be enhanced by activation of prejunctional beta 2 adrenoceptors in vivo. PMID- 2884806 TI - Alpha2-adrenoceptor agonists inhibit the migrating myoelectric complexes of the small intestine in rats. PMID- 2884807 TI - [Evaluation of the efficacy of haloperidol decanoate]. AB - A study was performed to establish the efficacy of haloperidol decanoate used as a drug to replace other neuroleptics, previously applied orally and daily to hospitalized chronic psychotic patients, clinically stabilized. For this study, 30 patients received one injection of this preparation every 4 weeks, during 4 months. After reviewing the results, it is concluded that this drug is very useful in these patients. PMID- 2884808 TI - Skin conductance nonresponding and nonhabituation in schizophrenic patients. AB - Bilateral skin conductance (SC) and heart rate (HR) were measured for 18 RDC diagnosed schizophrenic patients during rest and during presentation of identical tones. Computed tomography scans were evaluated. All but two patients were on neuroleptic medication. Six patients were nonresponders, seven habituated to the tones and five were nonhabituators. Nonresponders had lower SC level, fewer SC spontaneous fluctuations and higher HR level than the other subgroups. On neuropsychological tests the performance of the habituator group was closest to that of healthy subjects. Nonresponders did not differ in clinical symptoms, anamnestic data or in the prevalence of psychiatric morbidity in their families. Seventeen percent of the nonresponders had poor premorbidity adjustment vs 80% of the nonhabituators. Nonhabituators had higher ranks in the following symptoms: Presence of commenting voices, and inability to feel. They also tended to have wider third ventricles than the other two subgroups. The results support earlier findings in our laboratory suggesting nonhabituators as an important subgroup among schizophrenic patients. PMID- 2884809 TI - Delusional misidentification of the Capgras and intermetamorphosis types responding to clorazepate. A case report. AB - A patient with chronic psychosis and intermittent psychotic misidentification of the Capgras and intermetamorphosis types refractory to neuroleptic treatment was given a trial of clorazepate. Complete remission of psychotic symptoms was achieved for the first time in 19 years, but these recurred when the patient discontinued her clorazepate. It is concluded that clorazepate may be a useful treatment for some cases of chronic psychosis and psychotic misidentification. A possible mechanism for this is discussed. PMID- 2884810 TI - Schneiderian first rank symptoms: reconfirmation of high specificity for schizophrenia. AB - The prevalence of Schneiderian first-rank symptoms (FRS) in 294 consecutive admissions to a research unit was evaluated with reference to their diagnostic distribution (SADS/RDC). Thirty-five of 58 patients with schizophrenia had FRS, as compared to nine of 190 patients with major depressive disorder. All patients with two or more FRS received a diagnosis of schizophrenia. In the absence of organic or toxic etiology, the specificity of FRS for schizophrenia was 95% and their predictive value was 90%. These findings indicate that FRS should be regarded as strongly suggestive of schizophrenia in the absence of an organic syndrome. PMID- 2884811 TI - Comparison of the serum levels in primary non-agitated depressed out-patients treated with imipramine in combination with placebo, diazepam or dixyrazine. AB - Sixty-three non-agitated depressed out-patients were selected according to the Feighner-Robins-Guze criteria for primary depressions for a double-blind, between patient randomized study for an 8 week duration. All the patients were treated with imipramine following a fixed dose schedule for the first 2 weeks and thereafter according to clinical response (100-200 mg/day). This treatment was combined with either placebo, diazepam (10 mg/day) or dixyrazine (50 mg/day). The serum concentration of imipramine both at 2 weeks and later was significantly higher (P less than 0.05) in the group treated with dixyrazine than in the other two groups. In the group treated with diazepam, the serum levels of imipramine and desipramine were significantly lower than in the placebo group. The serum concentrations of diazepam, desmethyldiazepam and dixyrazine were almost unchanged during the study. No significant correlation was found between the dosage and the serum concentration of imipramine or desipramine. The change in mean CPRS-score correlated neither with the imipramine nor with the desipramine serum levels, it did correlate but negatively with the degree of side effects. The degree of side effects correlated positively with the serum concentration of desipramine. PMID- 2884812 TI - Depressed melatonin secretion in patients with nightmares due to beta adrenoceptor blocking drugs. AB - Nocturnal urinary melatonin excretion was evaluated in six patients with nightmares and hallucinations during treatment with beta-adrenoceptor blocking agents, and compared to six control patients with similar diagnoses and treatment but without such symptoms from the central nervous system (CNS). Nightly melatonin excretion was lower in all cases with nightly CNS-symptoms than in the control patients. The results also suggest drug differences and dose dependency. It is concluded that in predisposed patients CNS side-effects induced by beta adrenoceptor antagonists are related to depressed nightly melatonin secretion. PMID- 2884813 TI - Hemodynamic effects of loud noise before and after central sympathetic nervous stimulation. AB - The hemodynamic effects of loud noise after central alpha 2-adrenoceptor stimulation were studied in 13 patients with mild (WHO 1) essential hypertension. The patients were randomized (double-blind) to treatment with either placebo or guanfacine 1-2 mg for four weeks and then crossed over and treated for another four weeks. All patients were exposed to a loud broad-band noise (105 dBA for 30 min) and all were studied both on placebo and guanfacine. Guanfacine significantly reduced the resting blood pressure from 141/92 to 134/88 mmHg (p less than 0.01) as well as heart rate at rest from 63 to 58 beats/min (p less than 0.05). Noise stimulation caused a significant increase in blood pressure and resistance in the placebo-treated group, while cardiac output decreased significantly. Pretreatment for one month with the central alpha 2-adrenoceptor stimulating agent guanfacine did not block the noise-induced pressor response nor the increase in peripheral resistance. A significant decrease in stroke volume was observed and cardiac output also tended to decrease in this group. It could be concluded that loud noise is a potent pressor stimulus which causes vasoconstriction and that the blood pressure response during noise could not be blocked by the centrally acting antihypertensive agent guanfacine. Since noise causes vasoconstriction it also induces an increased tone in the small arteries and, if the noise stimulus is sufficiently strong and repeated for a long time, it might cause structural changes in the resistance vessels and permanent arterial hypertension in humans. PMID- 2884814 TI - Vasculitis--clinical aspects and therapy. PMID- 2884815 TI - Hypothalamus: past, present, future. PMID- 2884816 TI - Somatostatin and GHRH: mood and behavioral regulation. PMID- 2884817 TI - Coexistence of classical transmitters and peptides with special reference to the arcuate nucleus--median eminence complex. PMID- 2884818 TI - Importance of the neuroendocrine system in aging processes. PMID- 2884819 TI - Brain diseases in the elderly: clinical aspects and management. PMID- 2884820 TI - Multiple signals in synaptic transmission: impact on the strategies for the development of a new generation of centrally active drugs. PMID- 2884821 TI - In situ hybridization histochemistry: a new tool for studying brain function. PMID- 2884822 TI - Modulatory interactions between steroid hormones, neurotransmitters and neuropeptides in hippocampus. PMID- 2884823 TI - Beta-blocking agents and plasma lipids: an update. PMID- 2884824 TI - [Acute arthroscopy in children]. AB - The diagnostic value of arthroscopy in hemarthrosis of unknown origin of the knee joint in children is analysed on the basis of reports in the literature and our own patients. Of a total of 325 acute arthroscopies, 12 were carried out in children. 14 individual findings were made: 3 ruptures (non osseous) of anterior cruciate ligament, 4 meniscal tears, 4 osteochondral lesions, 1 cartilage damage in spontaneously repositioned patellar luxation and 2 other findings. Surgical treatment was indicated in 7 out of the 12 children. Acute arthroscopy is rarely employed in children. This is because corresponding injuries are very much rarer as a whole and not because the conditions are less serious. In our opinion, acute arthroscopy is called for in a greater number of pediatric patients than previously practiced. PMID- 2884825 TI - [Acute slipped femur head epiphysis. Causes--surgical treatment--results]. AB - The juvenile slipped capital femoral epiphysis depends on a dysendocrinia during puberal acceleration. The weakening of mechanical stability of the epiphyseal cartilage leads in most of the cases to a slow, only in some cases to an acute dorsocaudal slipping of the capital femoral epiphysis. Representation of our own patients of Orthopedic University Hospital D-Homburg/Saar with altogether 27 acute slipped capital femoral epiphyses during the years 1965-1981. The early operative stabilisation seems to be most important for a good prognosis (danger of development of femoral head necrosis). The opening of the hip joint during the operation by a ventral capsulotomy facilitates the reduction and decompresses the haematoma. In consideration of the mostly slow beginning, in many cases an ideal correction could not be achieved in most of the patients. In contrast to the osteosynthesis by screws the growth in length is less influenced by using a lamellar nail or Kirschner-wires. In cases of an acute slipped capital femoral epiphysis a first conservative treatment with subsequent correction osteotomy does not seem to be justifiable, because the danger of femoral head necrosis raises drastically. In case of opportune operation and correct technique good to fair functional results can be achieved. PMID- 2884826 TI - [Fatigue fracture of the proximal tibia in childhood--diagnostic and differential diagnostic problems]. AB - Two cases of fatigue fractures of the proximal tibia of boys, 11 and 14 years old are reported. Clinical and radiological findings are discussed with special regard of the literature. Especially differential diagnostic problems, even with actual methods are discussed. An histological examination is necessary only in doubtful cases. An precise anamnesis, clinical and standard X-ray examination are very often sufficient to get an exact diagnosis. PMID- 2884827 TI - [Femoral fractures near the knee in the growth period]. AB - Fractures of the distal part of the femur in children are difficult to classify as suggested by Aitken, Harris and Salter if the epiphyseal cartilage is injured. Such injuries are rare if seen in relation to the grand total of paediatric lesions. There are late complications, however. In unilateral closure of the epiphyseal cartilage growth will be irregular and there will be differences in leg length. The sequels to knee joint distortions with ruptures of the ligaments are significant. These ruptures will also result in leg malpositioning due to epiphyseal closure. Corrective measures are often necessary to straighten out the axial deviation and to compensate the differences in leg length. The authors' own patient material comprises besides epiphyseal fractures eight such ligamentous lesions with late complications. PMID- 2884828 TI - [Significance of rotation errors in supracondylar humeral fractures in the child]. AB - To get information about the importance of malrotation for posttraumatic varus or valgus deformity a clinical, radiological and CT follow-up examination of 20 children who were treated for supracondylar fracture from 1983 to 1985 was done. Rotational-displacement was measured on computed tomographical images taken from the region where fracture had happened. On the ap follow-up X-ray from both, the fractured and the other side, and the X-ray which was made after reduction, the medial and lateral colonne were measured from a "special point" in the middle of the shaft of the humerus. The length of the colonnes and their difference were compared. 15 of the 20 patients showed internal malrotation, 1 patient external malrotation and 4 showed no rotational-displacement. In 15 of the 16 patients with malrotation, the rotational-displacement caused a change in the length of the colonnes. Just in one case malrotation caused a minimal deformity of the carrying angle without alteration of the length of the colonnes. 93% of the cases with internal malrotation showed varus deformity. In 3 cases we saw growth disturbance of the epiphyseal plate, but the induced alteration of the length of the colonnes were minimal compared with the changes caused by malrotation. PMID- 2884829 TI - [Pathological fractures in childhood and adolescence in benign and semi-malignant bone tumors and tumorous and inflammatory bone changes]. AB - The article reports on etiology, clinics and treatment of pathological fractures caused by benign, semimalign bone tumors as well as tumorlike lesions and inflammatory bone alterations in childhood. Our patients treated between the years of 1972 and 1986 were reexamined and the results reconsidered thoroughly. Of 47 children with pathological fractures 38 were treated surgically. The treatment consisted of tumor excision or milling out respectively, perforation of the excavation and its subsequent filling with autologous spongiosa combined with additional stabilization by osteosynthesis. With this surgical therapy 3 recurrent cysts were observed of which one resulted in a refracture. With the majority of the children the pathological fracture lead to the discovery of the tumor. PMID- 2884831 TI - [Dynamization of fixateur externe]. PMID- 2884830 TI - [Pediatric skull fractures]. AB - In this study we analyzed neurocranial fractures of 116 children up to the age of 12. The changes of the anatomical skull structure during the child's development, the pathogenesis, diagnosis and treatment of the different kinds of skull fractures and methods for a sufficient prophylaxis to avoid them are discussed in the following. PMID- 2884832 TI - Human marrow transplantation: an immunological perspective. PMID- 2884833 TI - Approaches to the study of vector specificity for arboviruses--model systems using cultured mosquito cells. PMID- 2884834 TI - Stage-specific homocytotropic antibody response of Mastomys natalensis to Dipetalonema viteae infection. PMID- 2884835 TI - Pathogenicity of Crithidia fasciculata in the haemocoele of Glossina. AB - The mosquito flagellate Crithidia fasciculata produces intense haemocoelic infections following intrahaemocoelic inoculation into 5 species of Glossina--G. austeni, G. fuscipes fuscipes, G. morsitans morsitans, G. palpalis gambiensis and G. tachinoides. All Glossina inoculated with C. fasciculata died between days 4 and 9. Neither Trypanosoma brucei procyclics nor Leishmania hertigi promastigotes similarly inoculated into Glossina species, at the same dose, multiplied within the haemocoele and no deaths were recorded during the first 10 days post injection. No mortalities amongst sham-injected controls occurred over the 10-day period. PMID- 2884836 TI - The effect of trypanocidal drugs on the transmission of Trypanosoma brucei brucei by Glossina morsitans centralis. AB - The effects of trypanocidal drugs on Trypanosoma b. brucei infections in Glossina m. centralis have been investigated. Pentamidine and suramin exhibited no significant effects but both berenil and samorin reduced the number of salivary gland infections in comparison with controls. Berenil at concentrations of 10, 1.0 and 0.1 microgram/ml significantly reduced the number of mature infections when fed to flies throughout the whole period of trypanosome development. A similar result was obtained with samorin at 0.1 microgram/ml. Subsequent experiments showed that administration of both drugs at an early stage was more effective in preventing the maturation of infection than a later but more prolonged administration. Reported drug levels in the blood of different experimental host animals are of the same magnitude as those used here. It is suggested that repeated feeding of T. b. brucei infected Glossina on drug-treated hosts may reduce transmission, although alternative bloodmeal sources would reduce this effect. These influences are worthy of investigation in the field. PMID- 2884837 TI - Lectin-binding characteristics of Wuchereria bancrofti microfilariae. AB - The binding of 10 different lectins to the surface of microfilariae of Wuchereria bancrofti has been investigated. Wheat germ agglutinin (WGA) and Helix pomatia lectin (HPA) bound specifically to the sheathed microfilariae indicating the presence of N-acetyl-D-glucosamine and N-acetyl-D-galactosamine respectively on the surface. Exsheathed microfilariae did not react with any of the lectins. Treatment of sheathed microfilariae with proteases resulted in increased binding of WGA and HPA. Such treated microfilariae showed a weak binding of Concanavalin A (Con A), and lectins of lentil (LCH) and of Limulus polyphemus (LPA). Sheathed microfilariae incubated with sera of people living in endemic zones of filariasis but with no apparent evidence of infection (endemic normals), or with sera of chronic elephantiasis patients, or with their respective gamma globulin fractions, bound Con A and LCH. These lectins bound weakly to exsheathed microfilariae under the same conditions. Binding was due to the mannose components of the specific immunoglobulins of the sera which coated the microfilariae. However, microfilariae when incubated with sera or their globulin fractions from non-endemic normals (NEN), or from microfilarial carriers, did not bind Con A and LCH, suggesting that specific immunoglobulins were neither present in NEN sera nor in significant amounts in sera of microfilarial carriers. PMID- 2884838 TI - Immunity to Dipetalonema viteae (Filarioidea) infections in resistant and susceptible mice. AB - The course of infection with Dipetalonema viteae in mice shows marked genetically determined strain variation. Subcutaneous implantation of 5 female D. viteae into C57BL/10 (B10) mice results in a short term, low level microfilaraemia compared with that seen in similar infections in BALB/c mice. Adult worm survival is similar, thus the different patterns of infections reflect responses directed against the microfilariae larvae (mf). A number of immunological parameters have been monitored during infection in an attempt to identify strain differences which may be correlated with levels of resistance. Blast cell activity in the spleen and lymph nodes showed little strain difference, peaking on day 10 and declining as mf disappeared from the circulation. Total serum IgG levels doubled in both strains during infection, the response being more rapid in B10 mice. Serum IgM levels increased threefold in BALB/c mice but fourteen-fold in B10. Radiosorbent assays identified comparable anti-adult antibody and anti-mf homogenate IgM antibody responses in both strains. Immunofluorescent assay showed that the appearance of IgM antibodies directed against the mf surface correlated with the clearance of mf from the blood of B10 mice, whereas similar antibodies were not detected in BALB/c mice. It is proposed that the efficient clearance of mf in B10 is mediated through an IgM-dependent mechanism and that the chronic microfilariaemia seen in BALB/c mice is facilitated by the absence of a specific IgM response to mf surface antigens. PMID- 2884840 TI - Identification and selection of cattle naturally resistant to African trypanosomiasis. AB - Cattle were exposed to natural trypanosome challenge in an area of high Glossina density (Samandeni, Burkina Faso) for various periods of time during 1982, 1983, 1984 and 1985. All of 30 Zebu proved to be sensitive to trypanosomiasis i.e. they died or were treated in extremis in 10 +/- 4 weeks. Twenty-one (31%) Baoule were as sensitive as the Zebu while 47 (69%) were resistant i.e. they survived in good condition. Twenty Ndama/Baoule crosses, indigenous to Samandeni were all resistant. Weekly blood samples were taken (2,317 in total) for the determination of parasitaemia and packed cell volume (PCV) as a measure of anaemia, the most important pathological feature of cattle trypanosomiasis. In both Zebu and sensitive Baoule 59% of the blood samples showed positive parasitaemia, of which 38% and 52% respectively were T. congolense the major cattle pathogen in the area considered. In resistant Baoule and Ndama/Baoule 11% and 10% of the samples were positive for trypanosomes of which only 4% and 2% were T. congolense respectively. PCV decreased from 35 to 20 in Zebu, 39 to 20 in sensitive Baoule and 40 to 34 in resistant Baoule, there was no change in the indigenous Ndama/Baoule. Six Ndama/Baoule indigenous to Samandeni remained resistant to trypanosomiasis when moved to another area of high Glossina challenge. Seven Ndama/Baoule calves, conceived in Samandeni but born and kept for 2 1/2 years in a Glossina-free area, also proved to be resistant to challenge. Twelve Baoule calves, born from cattle selected under natural field challenge, and which had not come in contact with trypanosomes for the first 10 months of their life, proved to be resistant when exposed in the field. These observations show that some, but not all, cattle from the Baoule breed are naturally resistant to African trypanosomiasis, that this resistance does not need repeated exposure to trypanosomes early in life but appears to be inherited and functional against many types of antigenically different trypanosomes. Thus, selective breeding of trypanoresistant animals and their successful introduction, without trypanocidal drug protection, into areas of high Glossina density appears feasible. PMID- 2884839 TI - Different patterns of disease in two inbred mouse strains infected with a clone of Leishmania mexicana amazonensis. AB - We have infected BALB/c and C57BL/6 mice with a cloned Leishmania mexicana amazonensis population, obtained from the "Maria" strain. Progression of infection and histopathological examination confirmed the extreme susceptibility of BALB/c mice and the resistant pattern of the C57 BL/6. Anti-Leishmania antibody titers were higher in BALB/c than in C57BL/6 mice through the period of infection. Tests of delayed type hypersensitivity reaction with Leishmania antigens were positive in both strains in the beginning of the infection, but were negative later on in BALB/c mice. Our results are similar to those obtained with mixed parasite populations, and rule out the possibility of selection among different parasite subpopulations as responsible for the divergent course of the disease exhibited by these two strains of mice. PMID- 2884841 TI - Epidemiology of animal trypanosomiasis on a cattle ranch in Kilifi, Kenya. AB - A study of the epidemiology of animal trypanosomiasis was carried out on a 2500 ha cattle ranch, with a history of trypanosomiasis, in the Coast Province of Kenya in 1982. The tsetse survey on the ranch revealed one breeding focus of Glossina austeni in a thicket of approximately 50 ha. Trypanosomes were detected in 20% of the 46 dissected tsetse. During the study period of 9 months, 0.8% of the 3315 samples collected from 2300 Ayrshire X Sahiwal crossbred cattle were found infected with trypanosomes; 32% of 5909 samples collected from the same cattle had a packed cell volume (PCV) of 30% or less. Animals with a PCV of 30% or less were treated with a trypanocide (Berenil, Ethidium or Novidium). Antibody to trypanosomes was detected in 22.1% of the 343 sera collected from the cattle. A sentinel herd of 20 cattle was exposed for 182 days inside the tsetse infested thicket. All animals became infected with Trypanosoma congolense, on average after 53 days; they were subsequently treated with Berenil (6 mg/kg). A second, third and fourth T. congolense infection was diagnosed in 17, 11 and 1 animals, respectively. The cattle were treated similarly with Berenil after each of these infections. T. vivax and T. brucei were not diagnosed in the sentinel cattle. The results suggest that acquired immunity to T. congolense infection did not play a significant role in the sentinel cattle. PMID- 2884842 TI - Parasitological and serological surveys for malaria among the inhabitants of an aborigine village and an adjacent Malay village. AB - Malaria surveys in an Orang Asli (aborigine) and an adjacent Malay village showed significantly higher parasite rates in the age-group 0-9 years in the former. Parasite rates declined progressively from a maximum at 0-4 years in the Orang Asli to zero at 30-39 years while in the Malays it rose progressively with age. Indirect fluorescent antibody test (IFAT) titres against schizont antigens of Plasmodium falciparum and P. cynomolgi were higher in the Orang Asli in all age groups with a statistically significant inverse relationship between IFAT titres and parasite rates. IFAT titres in the Malay population also increased with age but were very much lower. Antibody levels detected by the enzyme-linked immunosorbent assay (ELISA) using soluble schizont antigens were also much higher in the Orang Asli and values with P. cynomolgi were higher than those with P. falciparum antigens. These differences are attributed to the higher malaria transmission in the younger age-groups of the Orang Asli and presumably greater immunological experience to a wider diversity of antigens than the Malays, thus explaining the presence of "protective" antibodies in the former but not the latter group. PMID- 2884843 TI - Israeli rickettsial spotted fever in children. A review of 54 cases. AB - We observed and recorded clinical and laboratory data from 54 children with fever and a maculo-papular rash admitted to Soroka Medical Center, Beersheva, Israel suffering from serologically confirmed rickettsial spotted fever. The rash generally began on the palms and soles and extended centripetally to the torso. Other clinical findings included myalgia, headache, hepatomegaly, and splenomegaly. None had a "tache noire". A left shift in the white cells, leucopenia, thrombocytopenia, hyponatraemia and impaired liver function tests were common laboratory abnormalities. All recovered following oral doxycycline therapy. Serious sequelae such as myocarditis, encephalitis, and disseminated intravascular coagulation, as reported in Rocky Mountain spotted fever, did not occur. PMID- 2884844 TI - Failure of Trypanosoma (Nannomonas) simiae to infect camels (Camelus dromedarius). PMID- 2884845 TI - Trypanosoma (Schizotrypanum) sp. indet. from a Maltese bat. PMID- 2884846 TI - [Urological management of female spinal cord injury patients--clinical survey of 28 cases]. AB - Most of the literature about the urological management of spinal cord injury patients is on male patients, and the method of the urological treatment for male spinal cord injury patients is often not useful for female patients. A clinical survey was done on 28 female neurogenic bladder patients after spinal cord injury treated at our Hospital between January, 1980 and January, 1985. At discharge, 11 patients (39.3%) were catheter free, 3 (10.7%) were managed by clean intermittent self catheterization, 1 (3.6%) was managed by clean intermittent catheterization by a helper, and 13 (46.4%) were on indwelling catheters. One of the main reasons that prevents female spinal cord injury patients from becoming catheter free is that there are no effective external collecting devices or devices to prevent urinary incontinence for female neurogenic bladder patients. Another reason is that some female patients can not obtain a high enough ADL level for toilet activities by rehabilitation in spite of lower thoracic or lumbar lesions. PMID- 2884847 TI - [Torsion of the undescended testicle: a case report]. AB - A 15-year-old boy was consulted to our hospital with the complaint of swelling of the left inguinal region with tenderness. Under the diagnosis of torsion of the undescended testicle, left orchidopexy was done with the finding of left testicle which had 360 degree counterclockwise intravaginal rotation. This was thought to be the 54th case of the disease in Japan. We have made some discussion on incidence, complication, diagnosis and therapy. PMID- 2884848 TI - Beta blockers: an effective treatment in congenital coronary fistulas to main pulmonary trunk in adults. PMID- 2884849 TI - Mechanism of alpha blockade for blood pressure control. AB - The realization that a generalized increase in peripheral vascular resistance was the fundamental hemodynamic abnormality in essential hypertension and that the maintenance of arteriolar tone depended on the continuity of the adrenergic nervous system led to the alpha-adrenoceptor inhibitors being the first substances to receive serious consideration as antihypertensive agents. An agent that inhibited the effect of the adrenergic transmitter at the neuroeffector junction was anticipated to be ideal in inhibiting adrenergic vasoconductor tone. The clinical expectations for these compounds in the treatment of arterial hypertension, however, were not fulfilled. Although they lowered blood pressure, the effect was accompanied by unacceptable side effects such as tachycardia, and tolerance rapidly developed. The realization that transmitter norepinephrine modulates its own release through a prejunctionally located, alpha-adrenoceptor operated control mechanism explained several paradoxical phenomena and suggested exciting therapeutic possibilities. Most important, it provided a plausible if not compelling explanation for the clinical failure of the classic alpha adrenoceptor inhibitors as antihypertensive agents. Characterization of the prejunctional and postjunctional effects of alpha agonists and antagonists led to the conclusion that prejunctional and postjunctional alpha adrenoceptors differed in receptor structure and led to the identification of prazosin as the first virtually specific alpha-adrenoceptor inhibitor. This was a crucially important step in the development of specific agents to combat adrenergic predominance in essential hypertension. Antihypertensive drugs like prazosin and doxazosin preserve feedback control of transmitter norepinephrine release, and consequently cause minimal reflex activation. They represent an alternative choice for therapy in all grades of hypertension with virtually no contra indicatons to their use. PMID- 2884850 TI - Effects of doxazosin on diet-induced hypercholesterolemia in C57BR/cdJ mice. AB - Plasma cholesterol levels are markedly reduced when doxazosin, a selective alpha 1-adrenoceptor inhibitor, is administered for several days to C57BR/cdJ mice that have been fed a high cholesterol diet. This system affords a useful model for investigating the mechanism by which selective alpha 1-adrenoceptor inhibitors decrease circulating lipid levels. The results indirectly suggest that hypercholesterolemia induced by dietary cholesterol may involve activation of the sympathetic nervous system. The basis for linkage between circulating cholesterol levels and sympathetic nervous activity, while not yet understood, may involve changes in the balance among cholesterol pathways in the liver, alteration of vasomotor tone and control of the activity of vascular endothelial lipases. An additive effect is described for cholestyramine and doxazosin, in which low density lipoprotein cholesterol is decreased by 76% by a combination of maximal doses of the 2 agents. PMID- 2884851 TI - Efficacy and safety of doxazosin in hypertension therapy. AB - In double-blind, controlled, parallel, comparative trials, the blood pressure lowering effect of doxazosin was compared with that of placebo and other active agents. In 1 large, multicenter study, 903 patients were evaluated: 408 patients received doxazosin; 323, active comparative agents (nadolol, metoprolol, prazosin or hydrochlorothiazide); and 172, placebo. In another smaller study doxazosin was compared with terazosin treatment. Doxazosin administered as monotherapy lowered blood pressure significantly when compared with baseline and the placebo-treated group. Doxazosin therapy resulted in substantial reductions from baseline readings for systolic and diastolic blood pressure in both the standing and supine positions; the effect of doxazosin was similar to that of the comparative drugs; however, unlike beta blockers, no significant change in heart rate was demonstrated. The effectiveness and safety of doxazosin are practically identical in young and elderly patients, as well as in blacks and whites. Doxazosin exhibited a favorable lipid profile and the reported side effects of doxazosin were comparable to those observed with placebo and other study drugs. Another multicenter trial reported that doxazosin therapy was effective at low doses; 76% of those responders achieved controlled blood pressure at a mean dosage of 3.3 mg daily. PMID- 2884852 TI - A multicenter trial of doxazosin in West Germany. AB - The antihypertensive efficacy and safety of the new long-acting selective alpha 1 inhibitor doxazosin were assessed in patients seen in clinical practice. A total of 232 mild to moderate hypertensive patients were treated by 35 physicians. After an initial 2-week period (phase 1) during which eligibility to enter the study was determined (diastolic blood pressure [BP] of 95 to 114 mm Hg), all patients received doxazosin 1 to 8 mg once daily for 8 weeks (phase 2). Patients were then maintained for another 4 weeks on the dosage necessary to control diastolic BP to less than or equal to 90 mm Hg (phase 3). Efficacy and toleration of doxazosin therapy during the study period were good; 81% of evaluable patients (n = 180) achieved BP control with a once-daily mean dosage of 3.3 mg. At the end of phase 2 BPs were reduced by (systolic/diastolic) 23.8/17.3 (sitting) and 23.7/17.1 mm Hg (standing). Side effects were generally mild to moderate and either were tolerated or disappeared with continued therapy; 7 patients withdrew from the study because of intolerable side effects. Overall results demonstrated that doxazosin is suitable for treatment of mild to moderate hypertension and can be administered on a once-daily basis, which enhances compliance. PMID- 2884853 TI - Plasma lipid lowering effects of doxazosin, a new selective alpha1 adrenergic inhibitor for systemic hypertension. AB - Hypertension and hypercholesterolemia are 2 major risk factors for atherosclerotic coronary artery disease (CAD). Elevations of both blood pressure and serum cholesterol levels should be reduced to control CAD risk. Doxazosin is a once-daily, long-acting, selective alpha 1-adrenergic inhibitor that is effective for the treatment of essential hypertension. During controlled studies of doxazosin's antihypertensive efficacy, 3 serum lipid parameters were measured; total cholesterol, total triglyceride and high density lipoprotein (HDL) cholesterol. In 10- to 12-week placebo-controlled studies, 142 doxazosin-treated patients were compared with 155 placebo-controlled subjects. Doxazosin patients had an increase of 8.9% in the HDL/total cholesterol ratio (p less than 0.05), whereas total cholesterol, HDL cholesterol and triglyceride levels were not significantly different between the 2 study groups. During a 52-week comparison of doxazosin versus atenolol, doxazosin treatment was associated with a significant decrease in total triglyceride levels (5%; p less than 0.001) and increases in HDL cholesterol levels (3.9%; p less than 0.01) and HDL/total cholesterol ratio (5.4%; p less than 0.0001). Doxazosin is an effective antihypertensive agent that has a favorable impact on serum lipid levels, thereby promoting a beneficial effect on 2 major CAD risk factors. PMID- 2884855 TI - An open one-year comparison of doxazosin and prazosin for mild to moderate essential hypertension. AB - The long-term safety, efficacy and effect on serum lipid profile of doxazosin, a new alpha 1-adrenoceptor inhibitor administered once daily, were compared with those of prazosin, administered twice daily, in 104 patients with essential hypertension treated for 1 year. Doxazosin produced clinically significant decreases in standing and supine blood pressures over a period of 1 year. These decreases were similar to those produced after an initial period of 12 weeks of double-blind therapy. The reductions in blood pressure produced by doxazosin were greater than those produced by prazosin. Minor and clinically nonsignificant changes in heart rate were observed with both drugs. The favorable changes from baseline in plasma lipid concentrations observed after 12 weeks of double-blind therapy were maintained throughout the 1-year open study. These were average increases in the mean high density lipoprotein cholesterol concentration and the derived high density lipoprotein/total cholesterol ratio, and average decreases in total cholesterol and total triglyceride concentrations. The incidence of side effects reported was similar for doxazosin and prazosin. Most were rated as being mild or moderate in severity and were tolerated or disappeared with continued therapy. Results of laboratory tests, electrocardiograms, ophthalmoscopy and body weight measurements revealed only minor changes from baseline, and none was judged to be of clinical significance. These findings demonstrate that doxazosin is a safe and effective antihypertensive agent suitable for once-daily dosing, and has favorable effects on the serum lipid profile. PMID- 2884854 TI - Serum lipid changes in a one-year, multicenter, double-blind comparison of doxazosin and atenolol for mild to moderate essential hypertension. AB - Proatherogenic changes in serum lipid concentrations have been implicated as one of the major risk factors in the development of coronary artery disease. In a double-blind study, the new alpha 1-adrenoceptor inhibitor, doxazosin, was compared with atenolol for effects on the serum lipid profile. Ninety-six hypertensive patients were treated for up to 1 year with either doxazosin or atenolol once daily. There were statistically significant differences (p less than or equal to 0.01) between doxazosin and atenolol after 20 to 52 weeks of treatment in changes from baseline total triglyceride levels, high density lipoprotein (HDL) cholesterol levels and HDL/total cholesterol ratio. The percentage of change from baseline and the statistical significance of the difference between treatment groups were: total triglycerides, doxazosin -5.9%, atenolol +32.4% (p = 0.01); HDL cholesterol, doxazosin +7.2%, atenolol -5.6% (p = 0.007) and HDL/total cholesterol ratio: doxazosin +8.7%, atenolol -6.2% (p = 0.006). All mean changes were in favor of doxazosin therapy. In addition, doxazosin treatment beneficially decreased total serum cholesterol levels (-1.6%) compared with atenolol (+0.6%), although not to a significant degree. The differences were maintained in the cohort of 67 patients treated for a full year. The favorable change exerted by doxazosin on the lipid profile suggests that it may have a beneficial influence on the lipid risk factor. These results, together with the sustained decrease in blood pressure achieved for up to 1 year of therapy, suggest that doxazosin may reduce the risk of coronary artery disease in susceptible patients. PMID- 2884856 TI - Multicenter, double-blind comparison of doxazosin and atenolol in patients with mild to moderate hypertension. AB - In a double-blind multicenter study, the new alpha 1-adrenoceptor inhibitor doxazosin was compared with atenolol for efficacy, safety and effect on serum lipids. One hundred and twenty-six patients with mild to moderate hypertension were randomly assigned to receive either doxazosin (n = 63) or atenolol (n = 63). The mean final dosages, administered once daily, to obtain 24-hour blood pressure (BP) control were doxazosin 12 mg (range 1 to 16) and atenolol 91.8 mg (range 50 to 100). Of 12 doxazosin and 7 atenolol patient withdrawals from the study, 7 doxazosin and 4 atenolol patients withdrew for treatment-related reasons. No statistically significant differences between treatment groups were found after 20 weeks in changes from baseline in standing and sitting BPs measured 24 hours after administration. Sitting BP (systolic/diastolic) was reduced by 10.5/9.8 mm Hg after doxazosin treatment and by 10.9/10.7 mm Hg after atenolol therapy. Standing BP was reduced by 8.8/7.7 mm Hg after doxazosin administration and 9.7/9.3 mm Hg after treatment with atenolol. Supine BP was measured in a small cohort of the study population, and doxazosin had a smaller effect than atenolol. After 20 weeks of treatment, both drugs reduced heart rate with atenolol producing a statistically significantly greater decrease than doxazosin (standing, doxazosin 5 beats/min, atenolol 16.2 beats/min, p less than 0.001; sitting, doxazosin 5 beats/min, atenolol 13.1 beats/min, p less than 0.001). Side effects were reported by 37 patients receiving doxazosin therapy and 34 patients receiving atenolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884857 TI - Pharmacokinetic overview of doxazosin. AB - After both oral and intravenous administration, doxazosin is extensively metabolized, with only about 5% of the administered dose excreted unchanged in urine. For single doses, oral bioavailability has been calculated to be about 65%; terminal elimination half-life is approximately 10 to 12 hours. In later multiple-dose studies in which doxazosin concentrations were measured beyond 24 hours after administration, the terminal elimination half-life was 22 hours. Clearance of doxazosin, presumably in the liver, involves the production of mainly O-demethylated and C-hydroxylated metabolites, and is low in comparison with hepatic blood flow. Protein binding is reported to be 98.3% in humans. Relatively low clearance (1.0 to 2.0 ml/min/kg) in association with a moderate volume of distribution (1.0 to 1.9 liters/kg) is responsible for doxazosin's relatively long plasma half-life. There is no evidence to suggest that active metabolites contribute significantly to the pharmacologic activity of doxazosin; both hypotensive effect and alpha-adrenoceptor inhibitor activity have been directly related to the concentration of doxazosin in blood. During long-term treatment, no significant changes in the disposition of doxazosin have been reported; with dosages up to the maximum clinically used dosage of 16 mg daily, there is no evidence of dose-dependent pharmacokinetics. Studies in elderly patients have shown no major pharmacokinetic differences. Overall, these pharmacokinetic results suggest that doxazosin is suitable for once-daily administration in the long-term treatment of patients with essential hypertension. PMID- 2884858 TI - Effects of alpha 1 inhibition on renal blood flow and sympathetic nervous activity in systemic hypertension. AB - Doxazosin is a competitive inhibitor of norepinephrine at alpha 1 adrenoceptors on vascular smooth muscle, where it blocks vasoconstriction. Twenty-four patients with mild hypertension were treated with either doxazosin or placebo for 6 weeks. Supine and upright mean arterial pressures decreased by 9 and 12 mm Hg, respectively, in patients receiving doxazosin. This decrease was significantly more than the blood pressure change with placebo (p less than 0.05). Doxazosin therapy led to a small increase in weight (p less than 0.05). It was also associated with a statistically insignificant decrease in renal vascular resistance (568 dynes s/cm5) so that renal blood flow and creatinine clearance did not change. Doxazosin increased renin levels acutely and norepinephrine levels with 6-week treatment, but these changes were not significantly different from placebo. Norepinephrine clearance, measured after a 120-minute infusion of 3H norepinephrine, did not change. Heart rate increased acutely after doxazosin administration, but returned to baseline during 6-week therapy. Blood pressure, measured hourly for 14 hours after treatment, was consistently decreased in all patients. Doxazosin taken once daily lowers blood pressure without affecting renal blood flow or heart rate. PMID- 2884859 TI - A double-blind parallel trial to assess the efficacy of doxazosin, atenolol and placebo in patients with mild to moderate systemic hypertension. AB - The antihypertensive and lipid effects of doxazosin and atenolol were compared in a 10-week, double-blind, parallel, placebo-controlled study. The 129 adults enrolled had mild to moderate hypertension (average supine diastolic blood pressures for doxazosin, atenolol and placebo were 100.6, 101.0 and 99.7 mm Hg, respectively). Patients were randomly assigned to treatment with doxazosin, 1 to 16 mg daily, atenolol, 50 to 100 mg daily or placebo. Among 114 patients included in the efficacy analysis, standing blood pressure (systolic/diastolic) changed by -13/-11 mm Hg with doxazosin (n = 37), -12/-12 mm Hg with atenolol (n = 39) and +1/-1 mm Hg with placebo (n = 38). Mean reductions in blood pressure for doxazosin and atenolol were significantly greater than those for placebo (p less than 0.01), although no statistically significant differences between the active agents were noted. Serum lipid measurements were evaluable for 116 patients, and the 38 doxazosin-treated patients in this group experienced reductions in total cholesterol, total triglyceride and very low density lipoprotein cholesterol levels. Both doxazosin and atenolol demonstrated comparable acceptance profiles. Doxazosin is an effective hypotensive agent with beneficial effects on serum lipid levels. PMID- 2884860 TI - Antihypertensive effects of doxazosin in systemic hypertension and comparison with terazosin. AB - A multicenter, double-blind study compared the antihypertensive efficacy and safety of doxazosin and terazosin as once-daily therapy. Doxazosin, a potent antihypertensive agent, selectively inhibits alpha 1 adrenoceptors. Its pharmacokinetic profile, including gradual onset of action, long plasma elimination half-life and long duration of action, permits once-daily dosing. Terazosin, a structural analog of prazosin, also inhibits alpha 1 adrenoceptors and is recommended as once or twice-daily therapy. Nineteen (73%) of 26 patients randomly assigned to receive doxazosin were therapeutic successes; 17 (65%) achieved normalized blood pressure (defined as blood pressure less than or equal to 90 mm Hg). The mean final daily dosage in patients classified as therapeutic successes was 2.4 mg. Eighteen (64%) of 28 terazosin-treated patients were considered therapeutic successes; 16 (57%) achieved normalized blood pressure. The mean final daily dosage in patients classified as therapeutic successes was 5.6 mg. Treatment-related side effects were observed in 30% of doxazosin-treated and 39% of terazosin-treated patients. Most side effects observed in either treatment group were mild or moderate and either disappeared or were tolerated with continued therapy. Doxazosin is an effective, well-tolerated, once-daily antihypertensive agent; it is comparable with terazosin but at a lower daily dosage. PMID- 2884861 TI - Comparative effects of doxazosin and hydrochlorothiazide on serum lipids and blood pressure in essential hypertension. AB - The efficacy and safety of doxazosin (mean dosage 6.9 mg, range 1 to 16) in the treatment of essential hypertension were compared in a double-blind study with those of hydrochlorothiazide (HCTZ) (mean dosage, 84.6 mg, range 25 to 100) in 104 hypertensive patients treated once daily for 6 months. Thirty-five patients were also assessed for comparative effects of the 2 agents on serum lipid parameters. Doxazosin produced potentially favorable changes from baseline in the concentrations of serum lipid fractions (total triglycerides, total cholesterol, high density lipoprotein [HDL] cholesterol and the derived HDL/total cholesterol ratio) compared with HCTZ. The decreases in total triglyceride and total cholesterol concentrations and an increase in the HDL/total cholesterol ratio were significantly different (p less than 0.006) from the opposite changes observed with HCTZ. Clinically relevant decreases from baseline in supine and standing blood pressures at 24 hours after administration did not significantly differ between the 2 agents. The incidence and severity of side effects were similar for both drugs. Three patients receiving doxazosin and 6 receiving HCTZ were withdrawn due to drug-related clinical side effects including 2 patients receiving HCTZ who were withdrawn because of laboratory test abnormalities. Eight HCTZ- and 1 doxazosin-treated patients developed hypokalemia and 6 HCTZ-treated patients developed hyperuricemia. These findings indicate that doxazosin and HCTZ provide comparable antihypertensive efficacy after 6 months of treatment using a once-daily regimen, but doxazosin produces a beneficial effect on the serum lipid profile as well as fewer biochemical aberrations. PMID- 2884862 TI - Conversion of paroxysmal atrial fibrillation to sinus rhythm by intravenous pirmenol. AB - The acute effects of pirmenol on atrial fibrillation were investigated in 40 patients with paroxysm of atrial fibrillation. Patients were randomized to receive either pirmenol, 50 or 100 mg intravenously, or placebo. Patients with congestive heart failure or a history of sinus node disorder were excluded. Sinus rhythm was achieved in 12 of 20 patients in 2 to 16 minutes after pirmenol administration and in 3 of 20 patients in the control group within 1 hour. A nodal escape rhythm during sinus slowing was observed in 1 patient. No sinus arrest, atrioventricular conduction disturbance or hypotension appeared. Pirmenol has an antifibrillatory effect on the atria. Sinus rhythm is restored rapidly after intravenous administration. Treatment of atrial fibrillation of recent onset was well tolerated in patients accepted for the study. PMID- 2884863 TI - Does dietary linolenic acid influence blood pressure? PMID- 2884864 TI - Evaluation of new anticancer agents against human pancreatic carcinomas in nude mice. AB - Heterotransplantation of human cancers in nude mice has provided an in vivo model for studying the biologic characteristics of human tumors, particularly their response to chemotherapy. In an effort to identify cytotoxic agents effective against pancreatic carcinoma, this model was used to evaluate the efficacy of three new anticancer agents--menogarol, 4'-epirubicin, and taxol--against two human transplanted pancreatic tumors. Relative area (tumor length X width) differed significantly between menogarol-treated and control groups (p = 0.034). A marked response was also observed in the tumors to 4'-epirubicin (p = 0.01). Taxol was ineffective in controlling tumor growth; by the fourth week, the size of treated tumors was similar to that of the control group (p = 0.55). No toxicity was observed in either the menogarol- or taxol-treated animals. Animals bearing the P2 tumor, and treated with 4' epirubicin displayed severe toxicity by day 18 with death by day 21 in most animals. For the second tumor, Capan-1, relative area differed significantly between the menogarol-treated and the control group (p = 0.003). In animals given 4'-epirubicin, a smaller difference was observed when comparing the relative areas (p = 0.09). Animals treated with taxol again showed no difference in the tumors when compared with controls (p = 1.0). The use of the nude mouse system has evolved so that tumor-oriented trials are now feasible with the hope of clinical applicability. This study illustrates that at least two agents--menogarol and 4'-epirubicin--may have some antitumor activity against pancreatic carcinoma in this system. PMID- 2884865 TI - Pediatricians' immunization consent practices in Washington state. AB - A survey of Washington state pediatricians and allied health professionals showed that two thirds provide written information to parents on diphtheria-tetanus pertussis; measles-mumps-rubella; and oral polio vaccines. Twenty-two percent of pediatricians provide written information on inactivated polio vaccine. Sixty-two percent of pediatricians who give immunizations require a parent's signature as evidence of having provided information or obtained consent. PMID- 2884866 TI - Hepatic toxicity during chemotherapy for severe tuberculosis meningitis. AB - The possible development of hepatotoxic effects as a result of high dosages of isoniazid, rifampin, pyrazinamide, and ethionamide was assessed in 56 young children (median age, 22 months) treated for severe tuberculous meningitis (TBM). Only one of the 56 children became jaundiced, probably as result of hepatitis A infection. Of 33 children observed for at least eight weeks, only five (15%) had normal serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase levels throughout, but in only three patients were AST or ALT values greater than 200 U/L, and enzyme levels tended to normalize toward the end of the period. In this group of 33 children, those at stage III TBM had higher enzyme levels than did those at stage II. The remaining 23 children were observed for a mean period of only four weeks, and 18 (75%) had at least one abnormal liver function test result. PMID- 2884867 TI - Human T-cell lymphotropic virus type I infection in neonates. AB - One hundred twenty-eight serum samples, collected from infants transfused at the neonatal care unit of Kyushu University Hospital, Fukuoka, Japan, were tested for the presence of antibody to human T-cell lymphotropic virus type I (HTLV-I) by the enzyme-linked immunosorbent assay and the indirect immunofluorescence test. Three of 128 were positive for anti-HTLV-I antibody. The three seropositive patients had received 62, 82, and 1160 mL of transfused blood. These patients did not receive any transfusion thereafter. In addition, no anti-HTLV-I antibodies were detected in the sera of their mothers and siblings. These data suggested that HTLV-I infection is one of the transfusion-associated complications in neonates. PMID- 2884870 TI - Accumulation of long asbestos fibers in the peripheral upper lobe in cases of malignant mesothelioma. AB - Animal studies suggest that mesothelioma is most effectively induced by fibers longer than 8 mu. However, studies of asbestos fibers recovered from human lungs in cases of mesothelioma indicate that, at least in large-scale samples, relatively few fibers meet this size criterion, perhaps implying that the animal data do not apply to man. Since asbestos concentration in lung is known to be extremely inhomogeneous, it is also possible that long fibers may selectively accumulate in specific sites, such as under the pleura. To examine this possibility, we selected ten cases of mesothelioma that contained relatively large amounts of amosite asbestos and extracted fibers from an 0.5-cm-thick strip of subpleural tissue and an area 3-cm deep to the subpleural sample for upper and lower lobes. Amosite fibers were identified and sized by electron microscopic techniques. Fibers in the peripheral upper lobe were significantly longer, broader, and of higher aspect ratio than those in the central upper lobe. The lower lobe showed a reverse pattern, with longer fibers and broader fibers in the central sample. These data indicate that the two lobes behave differently in regard to fiber size, with selective accumulation of long fibers in the peripheral upper lobe, but not in the peripheral lower lobe. Whether these differences reflect differences in initial deposition of fibers within the lung, or, more likely, specific redistribution of fibers, is unclear, but in either case, accumulation of long fibers immediately under the upper lobe pleura may be important in the genesis of mesothelioma. PMID- 2884868 TI - The coding sequence for the 32,000-dalton pulmonary surfactant-associated protein A is located on chromosome 10 and identifies two separate restriction-fragment length polymorphisms. AB - The primary protein component of human pulmonary surfactant is a 32,000-dalton glycoprotein called surfactant-associated protein A. This protein is important for normal lung function, and its expression is developmentally regulated. Using a mapping panel of somatic-cell hybrids, we have localized the coding sequence for pulmonary surfactant-associated protein A to chromosome 10. Additionally, this sequence identifies two separate MspI restriction-fragment-length polymorphisms. Since there is a relative lack of polymorphic markers for chromosome 10, this sequence may be useful in linkage analysis. PMID- 2884869 TI - Population genetics of coagulant factor IX: frequencies of two DNA polymorphisms in five ethnic groups. AB - Two frequently used restriction-enzyme polymorphisms (RFLPs) of coagulant F.IX, TaqI and XmnI, have been examined in five ethnic groups: white Americans, black Americans, East Indians, Chinese, and Malays. There is a distinct "cline" in the frequencies of both polymorphisms, from white Americans to Malays. The rarer type 2 alleles of both polymorphisms, in which middle recognition sites are present- and which in our sample reach their highest frequencies in white Americans--are marginally higher in four groups of Europeans previously reported by others. The frequencies of the rarer alleles are significantly higher in Europeans than in black Americans and East Indians, and these alleles are essentially absent in Chinese and Malays. The frequency of heterozygosity diminishes in the same order, being zero in Malays for both polymorphisms. The polymorphisms are in strong linkage disequilibrium, and in all groups the type 1 allele for TaqI is disproportionately accompanied by the type 1 allele for XmnI. The paucity of type 2 alleles and the low rate of heterozygosity in four non-European groups suggest that the polymorphisms will be of little diagnostic value south of Gibraltar and east of Suez. This prediction is confirmed by the observed haplotype frequencies in the black American and the Oriental groups. PMID- 2884871 TI - Assessing the efficacy of antianxiety agents. AB - Proper evaluation of anxiolytic therapy, involving the possible use of rating scales as well as the physician's skill in observation and communication, is essential in identifying the most appropriate treatment for a given patient and facilitating the management of therapy. These issues are discussed herein, using the clinical trials of buspirone, a new, nonsedating antianxiety agent, as a model for the process of drug selection. PMID- 2884872 TI - Impact of anxiety therapy on patients' quality of life. AB - The treatment of anxiety is one of the leading problems in medicine today. Although traditional anxiolytic drugs have been effective in reducing the symptoms of anxiety, their efficacy has often been achieved at the expense of the patient's quality of life. The sedative side effects and impaired psychomotor functioning associated with the use of benzodiazepine anxiolytics not only impede the success of therapy, but jeopardize the patient's safety. This article addresses these salient issues and provides evidence suggesting that the antianxiety drug buspirone better achieves the goal of optimal anxiolytic therapy with minimal unwanted effects. PMID- 2884873 TI - Alcohol and drug interactions with antianxiety medications. AB - The benzodiazepine anxiolytics are effective drugs that offer significant safety advantages over the pharmacologic treatments of anxiety that preceded them. However, problems still remain with the benzodiazepines, including their potential interactions with a variety of central nervous system depressant medications. This article reviews drug-drug interactions for an effective new non benzodiazepine anxiolytic, buspirone. To date, the data indicate that this drug does not potentiate the effects of measured amounts of alcohol and is less likely than diazepam to increase the number of side effects observed with a variety of prescription and over-the-counter drugs. When administered concomitantly on a short-term basis, buspirone does not seem to either potentiate or interfere with the effects of short- or long-acting benzodiazepine hypnotics. PMID- 2884875 TI - Gastrointestinal endocrine tumors: diagnosis and management. Role of somatostatin analogue SMS 201-995. July 4-6, 1986, Vancouver, British Columbia. Proceedings. PMID- 2884874 TI - Evaluation of the safety and side effects of antianxiety agents. AB - Historically, the use of anxiolytic drugs has been associated with a relatively high incidence of side effects, particularly those related to central nervous system depression and sedation. These side effects can impair the patient's ability to function and, thus, interfere with the full achievement of therapeutic goals. In this article, the evolution of anxiolytic drug therapy from the perspective of safety and side effects is reviewed. Moreover, data concerning the safety of buspirone--a novel, non-benzodiazepine anxiolytic that has been shown to provide anxiolytic efficacy comparable to that of the benzodiazepines, but with a significantly lower potential for central nervous system depressant effects, interactions with alcohol, dependence, and abuse--are discussed. PMID- 2884876 TI - Early surgical treatment of gastrinoma. AB - Medical treatment of the Zollinger-Ellison syndrome has been generally accepted because of the proven efficacy of the histamine (H2)-receptor antagonists in achieving symptomatic relief, and because of early reports indicating that few, if any, gastrinomas were resectable for cure. Gastrin radioimmunoassay (RIA) has made earlier and more certain diagnosis possible, and therefore reevaluation of the surgical management of gastrinomas is necessary. Experience with 60 gastrinoma patients is reported. Comparison between the pregastrin RIA years (before 1970) and post-gastrin RIA years was made to determine whether there was evidence to support the continuation of medical treatment without attempts to resect the gastrinoma. Twenty-five cases were diagnosed in the pre-RIA years. Age at diagnosis ranged from 17 to 68 years (median, 45 years). All patients were operated on. Metastases were found in 56 percent. No tumor was identified in 8 percent. Tumor was resected for "cure" (normal fasting gastrin levels for two years postoperatively) in one patient. Seventeen patients have died, and tumor was the cause of death in 70 percent. The five-year survival rate was 44 percent; the 10-year survival rate was 40 percent. Thirty-five cases were diagnosed after 1970. Age at diagnosis ranged from 39 to 61 years (median, 46 years). Thirty patients were operated on. Metastases were identified in 23 percent and no tumor was found in 17 percent. Tumor was resected for "cure" in 30 percent of patients. Seven patients have died and tumor caused death in 42 percent. The five-year survival rate was 82 percent; the 10-year rate was 64 percent. Advances in diagnosis and surgical technique since 1970 have made early operative treatment applicable in patients with gastrinoma. Because death in most cases is caused by progression of the tumor, an aggressive surgical approach to resect the tumor is advised soon after the diagnosis of Zollinger-Ellison syndrome is established. PMID- 2884877 TI - Glucagonoma syndrome. AB - The glucagonoma syndrome is characterized by a necrolytic migratory erythematous rash, angular stomatitis, painful glossitis, a normochromic normocytic anemia, mild diabetes mellitus, weight loss, a tendency to thrombosis, and neuropsychiatric disturbances. The diagnosis is made by finding a high plasma glucagon concentration in the absence of any other cause, such as renal failure or severe stress. A pancreatic alpha-cell tumor can be identified and stained by immunocytochemistry with glucagon antibodies. Optimal treatment is surgical removal, but approximately 50 percent of the tumors have metastasized by the time of diagnosis. Since the tumor is slow-growing, remission can be obtained by hepatic artery embolization to shrink hepatic secondaries or by shrinkage, in about 10 percent of patients, with the combination chemotherapeutic regimen of 5 fluorouracil and streptozotocin. The rash frequently responds to administration of zinc, a high-protein diet, and control of the diabetes with insulin. Alongside the alpha cell in the islets of Langerhans is the D-cell, which produces somatostatin and may well act physiologically as a paracrine inhibitor of glucagon release. A newly developed, long-acting somatostatin analogue, SMS 201 995, which the patient can self-administer as a subcutaneous injection, has proven effective in suppressing glucagon secretion from glucagonomas and, in some cases, causing remission of clinical symptoms. PMID- 2884878 TI - Carcinoids and carcinoid syndrome. PMID- 2884880 TI - Role of peptide radioimmunoassay in understanding peptide-peptide interactions and clinical expression of gastroenteropancreatic endocrine tumors. AB - Peptide radioimmunoassay has become an important clinical and research tool in understanding the role of peptides in the pathophysiology of gut endocrine tumor syndromes. A gut peptide radioimmunoassay laboratory has been established for the diagnosis and clinical monitoring of endocrine tumors of the gastroenteropancreatic (GEP) system. Radioimmunoassay has enhanced our awareness that co-occurring peptide interactions may modify and ultimately influence the clinical expression of these tumors. Furthermore, it has helped develop a rationale for the use of prototype peptides such as somatostatin and its long acting analogue Sandostatin (SMS 201-995) in the management of GEP tumors. This group's experience, as well as the experience of other investigators, is presented, and the clinical utility of peptide radioimmunoassay in the field of gut endocrinology is demonstrated. PMID- 2884879 TI - Effect of somatostatin analogue (SMS 201-995, Sandostatin) on pancreatic secretion in humans. AB - The effect of the long-acting somatostatin analogue SMS 201-995 on exocrine pancreatic function and hormone release was investigated in a double-blind, placebo-controlled study in healthy subjects. SMS 201-995 was administered subcutaneously at a dose of 25 micrograms twice daily, and all tests were performed 30 minutes after the morning injection. Pancreatic enzyme secretion, gall bladder contraction, and cholecystokinin response after a Lundh meal were completely inhibited by SMS, while pancreatic enzyme secretion elicited by intravenous injection of secretin and pancreozymin was suppressed by 80 percent. The inhibitory effect of SMS on endogenous cholecystokinin release was fully operative on the sixth day of injection treatment, whereas the inhibitory effect on exogenous cholecystokinin injection significantly decreased after SMS administration for seven days, indicating desensitization of the end organ by somatostatin. The release of pancreatic polypeptide by a solid test meal is abolished by administration of 25 micrograms of SMS, the release of gastric inhibitory polypeptide is nearly completely suppressed, the response of insulin and C-peptide are significantly lowered, and the gastrin response is only slightly reduced. PMID- 2884881 TI - Pseudopancreatic cholera syndrome: effect of a synthetic somatostatin analogue, SMS 201-995. PMID- 2884882 TI - Acromegaly. AB - At the time that acromegaly is diagnosed, more than half the pituitary adenomas are greater than 1 cm in diameter, and approximately half will not be cured by surgery or radiotherapy. Somatostatin, the natural hypophyseoportal peptide that inhibits the release of growth hormone, also inhibits the release of growth hormone from pituitary macroadenomas. Unfortunately, its plasma half-life is only a few minutes. With the development of a long-acting somatostatin analogue, SMS 201-995, prolonged therapy is possible. Several studies have demonstrated that when patients self-administer SMS 201-995 from two to three times daily at home, long-term inhibition of growth hormone release and remission of the clinical symptoms of acromegaly occur without significant side effects. SMS 201-995 is, therefore, a useful new palliative treatment for acromegaly. PMID- 2884883 TI - Rebound hypergastrinemia after cessation of a somatostatin analogue (SMS 201-995) in malignant gastrinoma. PMID- 2884884 TI - Asthma: emerging concepts and potential therapies. AB - Asthma is a disease of the airways that results in reversible airflow obstruction. Recent investigations have suggested that airway inflammation is associated with increased airway responsiveness and worsening of asthmatic symptoms. The role that mast cell mediators might play in the production of asthma has been investigated by use of newer analytical techniques and by use of fiberoptic bronchoscopy with lavage to obtain lower respiratory tract fluid and cells. In addition, new investigational compounds that interfere with the synthesis or action of inflammatory mediators have been tested. Developing lines of investigation suggest that chronic activation of inflammatory cells may be important in the pathogenesis of asthma. PMID- 2884885 TI - Beta-adrenergic stimulation of ion transport in primary cultures of avian salt glands. AB - Adrenergic stimulation of transmural ion transport was identified and characterized in primary cultures of avian salt gland. Adrenergic activation was mediated by beta-receptors since stimulation of the short-circuit current (Isc) was blocked by propranolol but not phentolamine. The Isc's elicited by isoproterenol, epinephrine, and norepinephrine were dose dependent, with respective EC50 values of 1.5 X 10(-8) M, 5.0 X 10(-6) M, and 1.1 X 10(-5) M. The apparent Ki for propranolol inhibition after isoproterenol stimulation was 7.5 X 10(-10) M. 8-Br cyclic AMP (8-Br cAMP) and forskolin-elicited Isc's that were insensitive to propranolol, were potentiated by theophylline, and inhibited by furosemide or ouabain. Isoproterenol also induced an increase in ouabain sensitive respiration in acutely dispersed cells from salt-stressed juvenile or unstressed adult animals, but not in fully salt-stressed adults. The data indicate that, in addition to the well-established cholinergic receptors, beta adrenergic receptors can control ion transport in these glands. Furthermore, the results suggest for the first time that an intracellular effector pathway involving cAMP is present. PMID- 2884886 TI - Gut-liver interaction in glutamine homeostasis: portal ammonia role in uptake and metabolism. AB - The role of ammonia released by the gut on hepatic glutamine handling and metabolism was studied in postabsorptive anesthesized male Sprague-Dawley rats at spontaneous and elevated arterial glutamine concentrations. Glutamine handling and metabolite release across both organ beds were studied using arteriovenous concentration differences and simultaneously measured portal and hepatic venous plasma flows. At the spontaneous arterial glutamine load, fractional glutamine extraction, FE-Gln, by the gut and the liver was 24 and 10%, respectively. At the elevated glutamine load, gut glutamine uptake doubled, while FE-Gln remained at 24%; however, portal ammonia and alanine increased and decreased, respectively. In response, hepatic FE-Gln increased to 28% with a large release of glutamate and urea. The role of portal ammonia in modulating hepatic glutamine uptake was studied by infusing NH4HCO3 directly into the portal vein. Increasing the portal load promptly stimulated hepatic glutamine uptake and glutamate and urea release. Mitochondria isolated from these livers produced more glutamate from glutamine, suggesting ammonia activation of hepatic glutaminase flux; in addition, citrulline formation increased, suggesting a coupling of glutaminase flux to urea synthesis. The results are consistent with portal ammonia release acting as a key informational molecule in interorgan glutamine flow. PMID- 2884887 TI - Role of pancreatic somatostatin in determining glucagon response to arginine and morphine. AB - It has been proposed that pancreatic somatostatin (SS) tonically inhibits pancreatic glucagon secretion. In keeping with this hypothesis, we have previously shown that infusion of a nonimmunoreactive analogue of SS, [D-Ala5,D Trp8]somatostatin (SSa), which in low doses inhibits SS secretion without inhibiting glucagon or insulin secretion, is associated with a large increase in glucagon and small increase in insulin secretion. Although direct stimulation of the alpha- and beta-cells by the analogue could not be excluded, high doses of the analogue appeared to inhibit insulin and glucagon secretion. These data therefore suggested that the effect of the analogue on insulin and glucagon secretion was indirect and due to reduction of tonic inhibition on the alpha- and beta-cells by SS. If pancreatic SS is an important regulator of glucagon secretion, then alterations in pancreatic SS should influence the glucagon response to secretagogues. Therefore, in the present study, we have examined the glucagon response to two different stimuli, arginine and morphine, either before or during suppression of pancreatic SS secretion. Intravenous injection of arginine produced a rapid increase of pancreatic glucagon output from the in vivo dog pancreas. When basal pancreatic SS output was suppressed by infusion of SSa, arginine injection produced a twofold larger glucagon response. Infusion of morphine directly into the pancreatic artery of the dog decreased pancreatic SS output and increased pancreatic glucagon output. When SS was suppressed by SSa infusion, morphine did not further suppress pancreatic SS secretion and the glucagon response to morphine was abolished.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884888 TI - Psychological and interpersonal issues in space. AB - As future manned space missions become longer, and as crews become more heterogeneous, psychological and interpersonal factors will take on increasing importance in assuring mission success. On the basis of a review of more than 60 American and Soviet space simulation studies on Earth, along with reports from U.S. and Soviet space missions, the author identifies nine psychological and seven interpersonal issues, which are discussed along with pertinent research findings and examples from manned spaceflights. He concludes that more psychological and interpersonal research should be done under actual spaceflight conditions and offers suggestions. PMID- 2884889 TI - Comparison of propranolol, sotalol, and betaxolol in the treatment of neuroleptic induced akathisia. AB - In earlier open studies, beta-blockers were found to be effective in the treatment of neuroleptic-induced akathisia. In the present study, 16 patients with severe neuroleptic-induced akathisia successively received low doses of three beta-blockers--propranolol, sotalol, and betaxolol. There was rapid and complete improvement in seven of 16 patients (and partial improvement in three patients) treated with betaxolol. The efficacy of propranolol and betaxolol and failure of sotalol in treating neuroleptic-induced akathisia suggest a central mechanism of action. PMID- 2884890 TI - Clonazepam treatment of adolescents with neuroleptic-induced akathisia. PMID- 2884891 TI - Neuroleptic malignant syndrome. PMID- 2884892 TI - The changing presentation of catatonia. PMID- 2884893 TI - Rapidly progressive hearing loss as a symptom of polyarteritis nodosa. AB - The hearing loss that occurs in polyarteritis nodosa is due largely to middle ear effusion but usually appears as a mixed type. Pure perceptive hearing loss is rare; only two cases have been reported previously in which sensorineural hearing loss was the initial sign of the disease. A case of profound, rapidly deteriorating perceptive hearing loss in which the etiology was not clear is described. One year after the onset of hearing loss, other manifestations of polyarteritis nodosa led to the diagnosis. PMID- 2884894 TI - [Neuroendocrine functional regulation of the reproductive system]. PMID- 2884895 TI - The effect of sufentanil on the cardiovascular responses to tracheal intubation. AB - The effects of sufentanil 0.5 or 1 microgram/kg, given intravenously after induction of anaesthesia, on the cardiovascular responses to tracheal intubation were examined in a controlled, randomised, double-blind investigation. The control group of patients exhibited significant rises in arterial blood pressure and heart rate for 4 minutes after tracheal intubation. Heart rate exceeded 100 beats/minute and systolic pressure increased by over 20% in every patient. All patients moved or breathed within 10 minutes of the administration of suxamethonium. Sufentanil 0.5 microgram/kg prevented increases in the mean values of heart rate and arterial blood pressure, although increases were observed in five patients. Significant falls in the mean values of heart rate and arterial pressure occurred from 4 minutes after intubation until observations ended 15 minutes after induction of anaesthesia. Two patients moved or breathed during this time, although movement in response to nerve stimulation occurred in all patients 10 minutes after administration of suxamethonium. Sufentanil 1 microgram/kg was effective in suppressing a rise in heart rate or arterial pressure in every patient. Significant falls in these variables occurred from 2 minutes after tracheal intubation onwards. No patient moved or breathed for 15 minutes after induction of anaesthesia, although neuromuscular transmission was present 10 minutes after giving suxamethonium in each case. PMID- 2884896 TI - Vecuronium infusions in patients with renal failure in an ITU. AB - The use of an infusion of vecuronium is described in seven patients with renal and respiratory failure in an intensive therapy unit. Neuromuscular function was monitored throughout using the train-of-four twitch technique. A bolus dose of vecuronium (0.1 mg/kg) was given, followed immediately by a continuous infusion (0.05 mg/kg/hour). The infusion rate was adjusted until the first twitch of the train was below 20% of control and then run at a constant rate. There was a marked variation in the dose of vecuronium administered (0.01-0.065 mg/kg/hour [corrected]). Two patients, who appeared to be most sensitive to the drug, were both receiving metronidazole. Recovery of neuromuscular function was extremely prolonged and widely variable (6-37 hours) on stopping the infusion. No adverse cardiovascular effects or evidence of histamine release were seen as a result of administration of the drug. Vecuronium is probably more suitable for administration in bolus doses rather than by infusion in patients with renal and respiratory failure. PMID- 2884897 TI - Assessment of alfentanil by intravenous infusion as long-term sedation in intensive care. AB - The use of an alfentanil infusion for sedation of critically ill patients in intensive care was investigated in 16 patients who were entered consecutively into the study. The mean duration of stay was 8 days. Supplements of Diazemuls and muscle relaxants were administered if required. The success of the technique was judged by nursing and medical staff and, in particular, the wakefulness of patients was noted. No patient could recall events that occurred during their infusion. An outline protocol is described. PMID- 2884898 TI - Inhibitor-treated microbial sensor for the selective determination of glutamic acid. PMID- 2884900 TI - Comparison of caudal and ilioinguinal/iliohypogastric nerve blocks for control of post-orchiopexy pain in pediatric ambulatory surgery. PMID- 2884901 TI - Unequal effects of cardiopulmonary bypass-induced hypothermia on neuromuscular blockade from constant infusion of alcuronium, d-tubocurarine, pancuronium, and vecuronium. PMID- 2884899 TI - Halothane selectively attenuates alpha 2-adrenoceptor mediated vasoconstriction, in vivo and in vitro. AB - The mechanism by which halothane interferes with catecholamine-induced vasoconstriction was examined, utilizing specific agonists at postjunctional alpha 1- and alpha 2-adrenoceptors on vascular smooth muscle. Stimulation of either adrenoceptor subtype normally produces vasoconstriction. Two experimental models of drug-induced vasoconstriction were used: in vivo blood pressure response in pithed rats, and in vitro isometric tension development in canine saphenous vein rings. These models were then utilized to examine the anti vasoconstriction properties of halothane. In vivo, halothane (1 MAC) produced a significant depression in the vascular response to azepexole (an alpha 2 adrenoceptor agonist), but halothane did not alter vasoconstriction by phenylephrine (an alpha 1-adrenoceptor agonist). Halothane caused a 24% reduction of maximal response (P less than 0.0001) to azepexole in pithed rats, and a 3.2 fold rightward shift of the log dose-response curve (P less than 0.0001). Similarly, in vitro, halothane significantly attenuated alpha 2- but not alpha 1 adrenoceptor responsiveness. Halothane (4%) depressed maximal vein contraction to azepexole by 26% (P less than 0.0001), and shifted the log concentration-response curve 2.4-fold to the right (P less than 0.0001). The observed selective interference with alpha 2-mediated vasoconstriction by halothane is unlikely to represent drug antagonism at the receptor level. Our observations may suggest, indirectly, that halothane interferes with Ca+2 entry into vascular smooth muscle. The phenomenon of selective anti-vasoconstriction at alpha 2 adrenoceptors by halothane may explain why alpha 1-adrenergic agonists often appear to retain their vasopressor activity during halothane anesthesia. The mechanism of halothane-induced vasodilation thus includes attenuation of alpha 2- but not alpha 1-adrenergic vasoconstriction; this further demonstrates the multifactorial nature of halothane-induced vasodilation. PMID- 2884902 TI - Evaluation of intense neuromuscular blockade caused by vecuronium using posttetanic count (PTC). PMID- 2884904 TI - Subacute hemodynamic effects of nebivolol in man at rest and during exercise. AB - In a subacute experiment 7 apparently healthy volunteers received a daily oral dose of 5 mg nebivolol for seven days, followed by a seven-day washout period with placebo. From the first day during treatment with nebivolol, peak exercise heart rate and systolic blood pressure, as measured during a standardized submaximal treadmill exercise, significantly decreased by 15% and 19% respectively. A prolonged treatment for one week did not further increase the response of exercise heart rate and systolic blood pressure to nebivolol. However, the ratio of preejection period (PEPc) to left ventricular ejection time (LVETc), an indirect and valuable measure of left ventricular performance, progressively and significantly decreased during the seven-day treatment period with nebivolol from a mean value of 0.37 +/- 0.012 to 0.31 +/- 0.009. The improvement of systolic time intervals resulted from a shortening of the PEPc and a lengthening of the LVETc. At rest, heart rate did not change significantly with nebivolol, whereas both systolic and diastolic blood pressure gradually and significantly lowered. The postexercise LVETc significantly shortened during treatment with nebivolol, and this shortening was more pronounced after seven days of treatment. After discontinuation of treatment with nebivolol, all these effects persisted for more than thirty hours after the last intake and gradually returned to pretreatment values thereafter. From these data it appears that nebivolol effectively reduces blood pressure at rest and during exercise in healthy volunteers, beneficially influencing preload and afterload, as measured by systolic time intervals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2884903 TI - [A unique picture of juvenile arteriopathy: obliterative endarteriolopathy and sclero-hyalinotic periangiopathy]. PMID- 2884905 TI - [Failure of gastric lavage in severe drug poisoning. Value of esophagogastric fibroscopy]. AB - A case is reported of massive drug self-poisoning (more than 200 pills associated with slices of oranges) in which repeated gastric lavage failed to empty the stomach. An attempt to split up the amalgamated pills, adherent to the gastric mucosa, by fibre-optic gastroscopy failed and a gastrotomy was required. Endoscopy together with gastric lavage is indicated in certain situations to quickly empty the stomach and so shorten the course of the poisoning. Indications are the large number of pills swallowed, a poor result of the treatment, a worsening of the clinical condition despite treatment, and three positive gastric toxicological assays within the first 24 h. PMID- 2884906 TI - [Test dose for epidural anesthesia in patients treated with beta-blockaders]. AB - Two cases are reported, demonstrating the difficulty to verify the lack of inadvertent intravascular injection of local anaesthetic during epidural anaesthesia in patients under beta-blockers. The tachycardia usually elicited by intravascular injection of a local anaesthetic-adrenaline mixture does not occur in these patients. The alternative consists in measuring blood pressure at the second minute after a test injection. PMID- 2884907 TI - Effect of acepromazine, diazepam, fentanyl-droperidol, and oxymorphone on gastroesophageal sphincter pressure in healthy dogs. AB - Treatment of healthy dogs with 4 commonly used psychotropic or analgesic agents significantly decreased resting gastroesophageal sphincter pressure (GESP). Acepromazine decreased GESP by 35% (P = 0.02); oxymorphone decreased GESP by 38% (P less than 0.005); diazepam decreased GESP by 42% (P = 0.005); and fentanyl droperidol decreased GESP by 40% (P = 0.03). Therefore, esophageal manometric evaluation of gastroesophageal sphincter function should not be preceded by administration of these drugs. PMID- 2884908 TI - Inflammatory mediator receptors and asthma. AB - Many inflammatory mediators (histamine, prostanoids, leukotrienes, platelet activating factor, adenosine, bradykinin, and sensory neuropeptides) have been implicated in the pathogenesis of asthma and produce their effects by activating specific cell surface receptors. Activation of these receptors may result in contraction of airway smooth muscle, mucus and fluid secretion, microvascular leakiness, chemotaxis of inflammatory cells, and neuronal activation, indicating that the receptors are localized to a variety of cells. Recent studies have indicated that mediator receptor activation may lead to a response either by modulating adenylate cyclase or by stimulating breakdown of membrane phosphoinositides, which release intracellular calcium ions. The latter mechanism appears to predominate, at least in the case of airway smooth muscle receptors. Several receptors for inflammatory mediators have been characterized functionally and by direct receptor binding techniques, and receptor subtypes have been recognized. Several specific mediator receptor antagonists have been developed but are unlikely to have a major clinical effect because so many different mediators are likely to contribute to the pathology of asthma. Platelet activating factor, possibly by acting on specific platelet receptors, is able to increase nonspecific bronchial responsiveness in human subjects, so it is possible that specific receptor antagonists of this phospholipid mediator might reduce the enhanced responsiveness to other inflammatory mediators which occurs in asthma. PMID- 2884909 TI - Leakage of macromolecules from the tracheobronchial microcirculation. PMID- 2884910 TI - Spastic paraparesis and dual exposure to human T-lymphotropic virus type I and human T-lymphotropic virus type IV. PMID- 2884911 TI - Co-occurrence of the Reiter syndrome and acquired immunodeficiency. PMID- 2884912 TI - [Influence of antihypertensive treatment on the metabolism of lipoproteins]. PMID- 2884913 TI - [Selecting the optimal dose of a new antihypertensive agent. Its application to tertatolol]. PMID- 2884914 TI - [Comparative study of the effectiveness and acceptability of tertatolol 5 mg and acebutolol 400mg in the treatment of mild arterial hypertension]. PMID- 2884915 TI - [Effects of tertatolol on atherogenicity indices in normo- or dis-lipemic hypertensive patients]. PMID- 2884916 TI - [Evaluation of beta-adrenolytic activity. Structure-activity relationship]. PMID- 2884917 TI - Cellular and molecular biology of hormone- and neurotransmitter-containing secretory vesicles. PMID- 2884918 TI - Proton pumps and chemiosmotic coupling as a generalized mechanism for neurotransmitter and hormone transport. AB - Neuroendocrine secretory vesicles contain within their membranes a highly specialized H1-translocating ATPase responsible for the generation and maintenance of an electrochemical proton gradient, delta pH inside acidic, and delta psi inside positive. Coupled with a high internal buffering capacity and extremely low permeability of the membrane to protons, this proton pump can generate and maintain an intravesicular pH of 5.5, independent of the external pH, and transmembrane electrical potential of 60 mV. The chemiosmotic gradient has important implications for several functions of the secretory vesicles: (1) maintaining oxidizable substances (such as biogenic amines) in the unoxidized form; (2) stimulating (or inhibiting) peptide processing enzymes; (3) permitting precipitation of intravesicular protein complexes, thereby increasing the amount that can be stored within the vesicle; and (4) serving as the driving force for the uptake of certain hormones and neurotransmitters such as acetylcholine, biogenic amines, and ATP. By using the putative biogenic amine transporter as an example, it can be demonstrated that based purely upon the existence of a transporter in equilibrium with the electrochemical proton gradients, an amine concentration approaching 135,000 to 1 can be achieved. The bioenergetics of amine transport do not predict the molecular mechanism of amine translocation. By using kinetic analyses of amine accumulation under a variety of situations, however, initial information concerning the salient aspects of amine transport is being obtained. PMID- 2884919 TI - The H+-translocating ATPase of chromaffin granule membranes. PMID- 2884920 TI - Composition and transport function of membranes of chromaffin granules. Established facts and unresolved topics. PMID- 2884921 TI - The vacuolar ATPase is responsible for acidifying secretory organelles. PMID- 2884922 TI - The proton pump of synaptic vesicles. PMID- 2884923 TI - Disposition of drugs in the elderly. AB - Adverse drug reactions not only occur more frequently but are also of a more severe nature in the elderly. For warfarin and many of the psychoactive drugs, this is due mainly to an increased pharmacodynamic sensitivity to the actions of these drugs. For a number of other drugs, old age is associated with changes in their distribution and eventual elimination from the body. This increases the risk of a relative overdose during routine use of the drug. Such risks can be minimised by the judicious adjustment of the dosages of these drugs. PMID- 2884924 TI - [Acute pancreatitis complicating biliary distomatosis caused by Fasciola hepatica in a patient with a choledochal diverticulum]. AB - A 43 years old man presented with acute pancreatitis following 13 years of mild grade hepatic colitis and angiocholitis. The absence of visible gall stone evocated the possibility of millithiasis. The operation discovered a big and hard head of the pancreas and an hypertrophied choledocal mucous membrane and the microscopic analysis of bladder's bile, ova of Fasciola hepatica. A control opacification on the 7th day revealed an adult fluke and a small diverticulum which were not visible on the roentgenogram at the time of the operation. Seven infusions of 60 mg de dehydroemetin permitted to eliminate the fluke with only a peak of fever. The diagnostic, pathophysiologic and therapeutic implications are discussed. PMID- 2884925 TI - Somatostatin augments the spread of limbic seizures from the hippocampus. AB - The role of the neuropeptide somatostatin in limbic seizures was studied using electrical stimulation of the hippocampus in kindled rats. Cysteamine, an agent which selectively and reversibly depletes brain somatostatin stores, had a biphasic action. An early proconvulsant effect was seen within a few hours, consisting of prolonged electrographic seizures in the hippocampus and more severe behavioral convulsions. A later anticonvulsant effect, maximal at 1 to 2 days and dissipating within a week, was manifested by less intense behavioral convulsions without change in the duration of electrical seizure activity. Both effects were dose-dependent. No change in afterdischarge thresholds was detected at any time after the administration of cysteamine. Intraventricular administration of somatostatin to animals with behavioral seizures attenuated by cysteamine treatment restored the responses to precysteamine levels. We conclude that somatostatin facilitates the spread of seizures over limbic circuits from a region of focal seizure initiation. PMID- 2884926 TI - Isolation and characterization of a cDNA coding for human myeloperoxidase. AB - A cDNA encoding the carboxyl-terminal fragment of the human myeloperoxidase heavy chain was isolated and characterized. It was then used to determine the locations of the myeloperoxidase light and heavy chains in the polypeptide precursor. A cDNA library from poly(A)+ RNA from human leukemia HL-60 cells was constructed in pBR322 and screened by differential hybridization with enriched and depleted cDNA probes and then by hybridization with an oligonucleotide probe. A cDNA clone containing 1278 bp with an open reading frame of 474 bp and a 3' noncoding region of 804 bp was isolated. The amino acid sequence deduced from the nucleotide sequence consisted of 158 residues including a sequence of 14 amino acids known to be present in the heavy chain of the molecule. The cDNA also included a stop codon of TAG followed by a noncoding sequence that included a potential recognition site for polyadenylylation and a poly(A) tail. RNA transfer blot analysis with the cDNA probe indicated that myeloperoxidase mRNA was approximately 3.3 kb in length. In vitro translation of the mRNA selected by cDNA hybridization revealed preferential synthesis of a 74,000-Da polypeptide precursor that could be precipitated with anti-myeloperoxidase IgG. Antibodies specific for the heavy and light chains of myeloperoxidase were isolated from antiserum by affinity chromatography employing Sepharose columns covalently bound to the heavy or light chains. Antibodies specific for the light chain or the heavy chain readily precipitated the 74,000-Da precursor polypeptide. These results indicated that myeloperoxidase is synthesized as a single chain which undergoes processing into a light and heavy chain. Furthermore, the heavy chain of myeloperoxidase originates from the carboxyl terminus of the precursor polypeptide. PMID- 2884927 TI - Intramolecular crosslinking of gamma-glutamyl transpeptidase. AB - gamma-Glutamyl transpeptidase (rat kidney) is a heterodimeric glycoprotein (subunit molecular weights 52,000 and 25,000). In addition to its single-chain biosynthetic precursor (Mr 78,000), glycosylated high molecular weight forms (Mr 85,000-95,000) have been reported in various rat tissues as well as during in vitro translation of its mRNA. Studies reported here suggest that these might be attributed to the anomalous behavior of intramolecularly crosslinked species. Thus, chemical crosslinking of the purified enzyme (as well as enzyme on the renal brush border membranes) by bifunctional reagents such as dimethyl suberimidate and by an active site-directed reagent, diazotized p-amino hippurate, produces stable heterodimers which exhibit molecular weights identical to that of the native enzyme when subjected to gel filtration. However, when subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the crosslinked species exhibit apparent Mr values of 85,000 to 110,000, depending upon the crosslinking agent used. Protein glycosylation alone does not account for such anomalous electrophoretic behavior; the extent and the regions of the enzyme involved in formation of crosslinks appear to exert considerable constraints upon their conformation even in denaturing media. PMID- 2884928 TI - The defective proton-ATPase of uncA mutants of Escherichia coli: ATP-binding and ATP-induced conformational change in mutant alpha-subunits. AB - Mutations in the uncA gene of Escherichia coli cause loss of both oxidative phosphorylation and ATP-driven generation of the transmembrane proton gradient. The uncA gene encodes the alpha-subunit of the F1-sector of the E. coli membrane proton-ATPase. F1-alpha-subunit from normal (unc+) E. coli binds ATP tightly (KD = 0.1 microM) and undergoes a large ATP-induced conformational change, but the functional role of the ATP-binding site is currently unknown. There is disagreement in the literature as to whether the ATP-binding site is present or lacking in F1-alpha-subunit from uncA mutant strains. One obstacle in studying this question is the difficulty of purifying mutant alpha-subunits in native form. In order to circumvent this difficulty we have studied ATP binding and ATP induced conformational changes in mixtures of F1 subunits obtained by dissociating uncA mutant F1. Anti-alpha antibody was used in conjunction with immunoblotting to identify the alpha-subunits in the mixtures. Retention of native conformation by the alpha-subunits was demonstrated by the fact that the dissociated alpha-subunits were fully competent to repolymerize with other F1 subunits to yield intact F1 aggregate. The results show that, contrary to previous reports, alpha-subunits from three catalytically defective uncA mutants do indeed bind ATP and do undergo an ATP-induced conformational change. The binding affinity of alpha-subunit for ATP was lower than normal in each of the three mutants, but this is not likely to be a significant factor under physiological conditions. PMID- 2884929 TI - [Overview of ATL (adult T-cell leukemia) research]. AB - ATL is a unique T-cell malignancy first described by Takatsuki and colleagues in 1970s. We estimate that more than 300 patients a year have been detected in the endemic areas of Kyushu, Japan. The surface phenotype of ATL cells characterized by monoclonal antibodies is T3+, T4+, T8-, T11+ and Tac+. In all cases the serum is positive for anti-HTLV-I antibodies and the ATL cells contain the proviral DNA of HTLV-I. Variations in the clinical features of atypical ATL suggested a division of the spectrum of ATL into five types: acute; chronic; smoldering; crisis; and lymphoma. Typical ATL takes an acute course. The survival time is short, with 50% mortality within approximately 5 months. In general a poor prognosis is indicated by the elevation of serum lactate dehydrogenase, calcium, and bilirubin, as well as by high WBC. Smoldering ATL is characterized by the presence of a few abnormal cells (0.5%-3%) in the peripheral blood over a long period. Crisis in chronic or smoldering ATL means the progression of the disease to acute ATL. The lymphoma type of ATL is considered to be a form of T-cell-type non-Hodgkin's lymphoma in which malignant cells contain proviral DNA of HTLV-I. Screening of the sera from healthy adults for presence of the anti-HTLV-I antibodies revealed that 3.6% of healthy individuals in Kumamoto Prefecture, which is located in the middle of Kyushu, were HTLV-I carriers. Family studies showed that the routes of natural infection of HTLV-I are from mother to child and also from husband to wife. The borderline between the healthy carrier state and smoldering ATL remains unclear. Smoldering ATL is frequently diagnosed in patients with fungus infection of the skin, chronic lymphadenopathy, interstitial pneumonitis, chronic renal failure and strongyloidiasis. Five patients with ATL refractory to conventional chemotherapeutic agents were treated with 2'-deoxy coformycin (DCF), a potent inhibitor of adenosine deaminase. Two patients showed a good response, and three were resistant to DCF. In addition our experiences with a concurrence of lymphoma-type ATL in three sisters and spontaneous remissions in a patients with chronic ATL will be referred. PMID- 2884930 TI - Severe clostridium infection following perforation of the uterus in a patient with an ectopic pregnancy. AB - Twenty-eight hours after CO2 insufflation and curettage in a 26 year old, haemolysis, jaundice and anuria developed. As an ectopic pregnancy was also suspected, a diagnostic laparoscopy was done and was followed by a hysterectomy and left salpingo-oophorectomy before Clostridium perfringens was grown on culture. The survival of the patient despite clostridial infection is probably due to immediate surgical treatment and intensive post-operative care. PMID- 2884931 TI - [Fertility of patients operated on for unilateral undescended testis]. PMID- 2884932 TI - Effect of sulphasalazine on the radiological progression of rheumatoid arthritis. AB - We have investigated the influence of sulphasalazine, a second line antirheumatic drug, on the radiological progression of erosions in rheumatoid arthritis over a two year period in 41 patients. Hand radiograph scores deteriorated significantly over this period, but in a group of 31 patients in whom one year films were also available this deterioration was limited to the first year. This slowing of radiological deterioration was not related to 'normalisation' of the erythrocyte sedimentation rate (ESR). Compared with a 'control' group of 10 patients who had refused offers of second line therapy, sulphasalazine treated patients showed less deterioration over the two year period, and this difference was more marked than in previous studies of gold or penicillamine. No significant change was seen in large joint radiographs in sulphasalazine treated patients over two years, but this probably represents the poor sensitivity of the method of assessment. No significant correlation was seen between changes in inflammatory indices and slowing of radiological deterioration in erosion score. Thus sulphasalazine appears to slow the progression of radiological disease of the hands over the second year of treatment in a representative sample of patients who continue to receive treatment for two years. PMID- 2884933 TI - Raised circulating levels of the eosinophil cationic protein in ankylosing spondylitis: relation with the inflammatory activity and the influence of sulphasalazine treatment. AB - The possibility of eosinophil involvement in ankylosing spondylitis (AS) was investigated by measuring serum levels of eosinophil cationic protein (ECP), a specific granule constituent of eosinophils. In a group of 48 patients with AS we found a threefold increase of the mean serum levels of ECP compared with a reference group (p less than 0.001). The blood eosinophil counts were similar in patients and controls. A correlation was found between ECP and inflammatory activity defined by erythrocyte sedimentation rate (ESR) and serum haptoglobin. Fifteen patients were studied before and after three months' treatment with sulphasalazine (2-3 g/day). The ECP levels decreased in 13/15 and this paralleled reduction of the acute phase reaction and improvement of clinical parameters. The results point to eosinophil activation as part of the inflammatory process in AS. The signs of reduced eosinophil activation during sulphasalazine treatment suggest either a drug mediated, direct effect on eosinophils or an effect on the inflammatory mechanism stimulating eosinophils. PMID- 2884935 TI - Sulphasalazine and hepatic transaminases. PMID- 2884934 TI - Antibodies to the five histones and poly(adenosine diphosphate-ribose) in drug induced lupus: implications for pathogenesis. AB - Certain drugs are a frequent source of antinuclear antibody (ANA) induction, and ANA is invariably present in the few patients who progress to the drug induced lupus syndrome. This report concerns the fine specificity of the ANA response to hydralazine, penicillamine, and sulphasalazine therapy. Using highly purified individual histones in fluorimetric assays, antihistone antibodies are always detectable, often in large amounts, but the pattern of response to individual histones is variable and not drug specific. In addition to the response to the three histones H1, H2B, and H3 reminiscent of idiopathic systemic lupus erythematosus, antibody to histone H2A predominates in some drug induced cases. Contrary to previous thought, histones are not the sole target of the antinuclear response: we also demonstrate a significant correlation between ANA titre and antibody to poly(adenosine diphosphate-ribose). Like the histones, this is a macromolecule that can bind to deoxyribonucleic acid (DNA). It is proposed that drug induced damage to chromatin leads to ANA production, while drug induced impairment of complement activity may then enable these autoantibodies to mediate the lupus syndrome. PMID- 2884936 TI - Sulphasalazine in rheumatoid arthritis: desensitising the patient with a skin rash. PMID- 2884937 TI - Emotion control and cerebellar atrophy in senile dementia. AB - New research increasingly indicates that the cerebellum coordinates and integrates a wide range of processes not confined to the motor sphere. Since satisfying correlations between affective disturbances and signs of cerebral atrophy have not been found, the relationship of CT-indicated cerebellar atrophy to certain psychopathologic indicators, in patients suffering from senile dementia, has been studied. The patients participating in the study were 21 women and 18 men with a mean age of 69.4 years. Each patient showed a definite pathologic score in at least one cerebral CT-measurement. The Spearman rank correlations between affective incontinency, lability of affect, and cerebellar atrophy suggest substantial relationships between affective symptoms and cerebellar pathology. This seems all the more remarkable since all of the various indicators of cerebral cortical and subcortical atrophy lacked to show any strong relationship to affective symptoms at all. The implications of the findings for research and clinical purposes are discussed. PMID- 2884938 TI - Further evidence to support the alpha 2-adrenergic nature of amitraz-induced decrease in intestinal motility. AB - The effect of amitraz, a formamidine insecticide, on in vitro intestinal contractions was studied in teh transmurally-stimulated guinea-pig ileum. An electrical stimulation (with 80 V/0.5 msec/0.1 Hz shown on the dial of the stimulator) caused the ileum to contract presumably via the release of acetylcholine. Amitraz (10(-7) to 10(-6) M) produced a dose-dependent inhibition of these transmurally-stimulated contractions. This effect of amitraz was blocked and reversed by idazoxan (10(-6) M), an alpha 2-adrenoceptor antagonist, but was not prevented by prazosin (10(-6) M), an alpha 1-adrenoceptor antagonist. These results suggest that alpha 2-adrenoceptors mediate the effects of amitraz on the transmurally-stimulated guinea-pig ileum. The results also suggest that amitraz decreases intestinal contraction by activating the alpha 2-adrenoceptors in the myenteric (Auerbach's) plexus, thus inhibiting parasympathetic tone. PMID- 2884939 TI - Gastrointestinal transit following intrathecal or subcutaneous narcotic analgesics. AB - This paper reports investigations on the effects on gastrointestinal transit of subcutaneous or intrathecal administration of opiates: morphine, sufentanil and alfentanil. Subcutaneous administration of opiates produced a significant dose dependent decrease in transit of a charcoal meal test. Intrathecal administration of morphine to Wistar rats with catheter chronically implanted in the subarachnoid space did not cause a decrease in gastrointestinal transit. However, in freshly prepared rats with intrathecal catheter in the subarachnoid space, morphine significantly decreased intestinal transit of charcoal meal. In addition, sufentanil and alfentanil, on intrathecal administration in rats with chronically implanted catheters, caused a marked dose-dependent slowing of the passage of meal. Prior s.c. administration of the opiate antagonist naloxone completely blocked the depression of gastrointestinal transit caused by high doses of intrathecal sufentanil and s.c. administered morphine. PMID- 2884940 TI - Effects of two benzodiazepines and a benzodiazepine antagonist on neuromuscular blockade in the anaesthetized cat. AB - The interaction of diazepam and midazolam with non-depolarizing neuromuscular blocking drugs was studied in the sciatic nerve-tibialis anterior muscle preparation of the anaesthetized cat. Both diazepam and midazolam (0.3 mg/kg i.v.) caused a significant enhancement of a constant 50% neuromuscular block, produced by infusions of vecuronium or pancuronium. Increasing the dose of midazolam from 0.3 to 1.5 mg/kg, caused no significant further potentiation of vecuronium, but decreased the onset time of potentiation. Ro 15-1788, a selective benzodiazepine antagonist, did not antagonize the vecuronium potentiation caused by midazolam 0.3 mg/kg. However, when given before midazolam (1.5 mg/kg), Ro 15 1788 delayed the onset of potentiation. Ro 15-1788 antagonized and prevented the considerable blood pressure decrease produced by midazolam 0.3 and 1.5 mg/kg. There appears to exist a ceiling to the benzodiazepine-induced blood pressure decrease and potentiation of vecuronium in the cat. PMID- 2884941 TI - Antihypertensive, hemodynamic and autonomic profile of a new angiotensin converting enzyme inhibitor, SCH 33844 (spirapril). AB - SCH 33844 is a new, potent and long-acting inhibitor of angiotensin converting enzyme (ACE). Antihypertensive, hemodynamic and autonomic actions of SCH 33844 were examined in the present series of experiments. Oral administration of 0.3-30 mg/kg reduced blood pressure of spontaneously hypertensive rats. The magnitude of the response was significantly enhanced by pretreatment of the animals with hydrochlorothiazide. Blood pressure remained significantly depressed 24 hr following doses of 3 and 10 mg/kg. Administration of SCH 33844 (3 mg/kg) twice daily to nonpretreated rats or once daily to diuretic-pretreated animals for 5 days resulted in a progressive decrease in blood pressure. The compound did not reduce blood pressure in nephrectomized rats demonstrating the dependence of its action on renal renin. SCH 33844 (1-10 mg/kg orally) also produced dose-related decreases in pressure in diuretic-pretreated conscious normotensive dogs. However, only a small fall in pressure occurred in non-pretreated dogs. Hemodynamic actions were examined in anesthetized dogs. SCH 33844 (1 mg/kg i.v.) reduced blood pressure, increased cardiac output and caused a large fall in peripheral resistance. Autonomic actions were assessed in pithed rats. The compound (10 mg/kg orally) tended to decrease pressor responses to sympathetic activation and to i.v. norepinephrine. This profile is probably due, at least in part, to vasorelaxation following suppression of angiotensin II generation. In conclusion, SCH 33844 is a potent, long-lasting antihypertensive agent which reduces peripheral vascular resistance and possesses only slight autonomic effects. PMID- 2884942 TI - Multiple endocrine neoplasia type 2b with a good prognosis. AB - Three patients with the multiple endocrine neoplasia syndrome type 2b (MEN 2b) and a good prognosis are described. During a follow-up period of 41 to 84 months, only little progression of metastases of medullary carcinoma of the thyroid was observed. In one of the patients, liver metastases of medullary carcinoma of the thyroid were already present in biopsy specimens taken 22 years earlier. In two patients bilateral pheochromocytomas were completely removed. These observations show that, in contrast to the general view, the clinical course of MEN 2b can be as indolent as that of MEN 2a or sporadic forms of the tumors involved, despite the presence of metastases. This may indicate that factors other than the type of inheritance contribute to the outcome of the disease. PMID- 2884943 TI - Partial characterization of DNA-dependent RNA polymerases from Entamoeba histolytica. PMID- 2884945 TI - [Development of a basic material for an axenic culture medium for Entamoeba histolytica. II. Peptones]. PMID- 2884944 TI - [Analysis of the organization of the DNA of various strains and clones of Entamoeba histolytica]. PMID- 2884946 TI - Isolation and initial characterization of DNA from Entamoeba histolytica HM1:IMSS. PMID- 2884947 TI - High salt SDS-DEP isolation of RNA from Entamoeba histolytica: the recovery of intact 25S rRNA from amebae of different culture ages and the co-isolation of DNA. PMID- 2884948 TI - [Castela texana: screening for its anti-amoebic activity]. PMID- 2884949 TI - [Localization and identification of adhemiba I, a protein which participates in the adhesion of Entamoeba histolytica to human erythrocytes and epithelial cells]. PMID- 2884950 TI - Adhesion of Entamoeba histolytica trophozoites to human erythrocytes. 1. Maintenance of the integrity, viability and adhesion of trophozoites in different media. PMID- 2884951 TI - Adhesion of Entamoeba histolytica trophozoites to human erythrocytes. 3. The inhibition patterns by carbohydrates are strain-specific. PMID- 2884952 TI - [Characterization of 3 mutants of Entamoeba histolytica deficient in virulence with different phenotypes for adhesion and toxin activity]. PMID- 2884953 TI - [Mitogenic and lectin activity of mutants of Entamoeba histolytica deficient in virulence]. PMID- 2884955 TI - Cytopathogenicity of Entamoeba histolytica; a cytoplasmic heat stable factor stimulates DNA synthesis in mammalian cells. PMID- 2884954 TI - [Multifactorial mechanism for the cytolytic activity of Entamoeba histolytica]. PMID- 2884956 TI - Alteration of isoenzyme patterns of a cloned culture of non pathogenic Entamoeba histolytica upon changes in growth conditions. PMID- 2884958 TI - [Acid phosphatase activity of 2 strains of Entamoeba histolytica of different virulence]. PMID- 2884957 TI - Anti-surface antibodies to Entamoeba histolytica and their role in complement lysis. PMID- 2884959 TI - [Diapedesis in experimental amebiasis]. PMID- 2884960 TI - [Experimental amebiasis in the guinea pig: a model for resistance]. PMID- 2884961 TI - [Immunogenicity of a delipidated antigen of Entamoeba histolytica]. PMID- 2884962 TI - [Inhibition by antibodies of the adhesion of trophozoites of Entamoeba histolytica]. PMID- 2884963 TI - In vitro studies on the interaction of human monocytes and the monocyte locomotion inhibitory factor produced by E. histolytica. PMID- 2884964 TI - [Ultrastructural changes associated with the inhibition of human monocyte chemotaxis caused by products of E. histolytica cultured in axenic medium]. PMID- 2884965 TI - [Effect of supernatants obtained from lymphocytes stimulated with concanavalin A on trophozoites of Entamoeba histolytica]. PMID- 2884966 TI - [Effect of cellular immunity on the interaction between the peritoneal cell and the ameba in vitro]. PMID- 2884967 TI - [Induction of a local humoral immune response against antigens of Entamoeba histolytica]. PMID- 2884969 TI - [Interaction in vitro of trophozoites of Entamoeba histolytica with macrophages from human colostrum]. PMID- 2884968 TI - [Detection of class IgA antibodies directed against a lipopeptidophosphoglycan of E. histolytica in samples of human colostrum]. PMID- 2884970 TI - [Genetic transformation in Entamoeba histolytica]. PMID- 2884971 TI - [Evaluation of cellular immunity in patients with amebic liver abscess using the leukocyte migration inhibition test]. PMID- 2884972 TI - [Clinical correlation of the zymodeme of Entamoeba histolytica in patients in a psychiatric hospital]. PMID- 2884973 TI - Epidemiology of amebiasis in a rural community of Mexico: serologic and coproparasitoscopic survey. PMID- 2884975 TI - [Epidemiology and control of amebiasis in Mexico]. PMID- 2884974 TI - [Cell-cycle phases of Entamoeba histolytica]. PMID- 2884976 TI - Amebiasis in the world. PMID- 2884977 TI - [Comparative study of zymodemes of Entamoeba histolytica and the genus Entamoeba in polyacrylamide gels]. PMID- 2884978 TI - [Production of E. histolytica HM-1 in agitated axenic culture and by fermenter]. PMID- 2884979 TI - [Purification of the polysaccharide portion of the lipopeptidophosphoglycan extracted from trophozoites of Entamoeba histolytica]. PMID- 2884980 TI - [Characterization of the ribosomal proteins of Entamoeba histolytica]. PMID- 2884981 TI - [Motility mutants of Entamoeba histolytica resistant to cytochalasin D]. PMID- 2884982 TI - [Phases of nuclear division in Entamoeba histolytica]. PMID- 2884983 TI - Multiple mesenteric aneurysms complicating subacute bacterial endocarditis. AB - Multiple visceral aneurysms complicating periarteritis nodosa are considered characteristic, though not pathognomonic, on arteriography. This arteriographic pattern has been described with hairy-cell leukemia, collagen vascular disorders, and atrial myxoma, but, to our knowledge, has not been previously reported with subacute bacterial endocarditis. A patient with enterococcal endocarditis sustained separate intra-abdominal hemorrhages, 24 hours apart, from aneurysms of the middle colic and left colic arteries. Sterile vessel cultures with inflammatory infiltrates, decreased complement levels, positive rheumatoid factor, and arteriographic evidence of multiple visceral aneurysms suggest the vasculitis was immunologically mediated and not mycotic. Antibiotic therapy after control of hemorrhage controlled abdominal symptoms. PMID- 2884984 TI - Insulinoma and gastrinoma in Wermer's disease (MEN I). AB - The association of gastrin- and insulin-producing tumors of the pancreas is rare. In the 30 years' experience of Zollinger and others, of 40 patients with gastrinoma none had insulin-producing tumors. In contrast to patients with Zollinger-Ellison syndrome, of whom 15% to 26% are classified as having multiple endocrine neoplasias type I (MEN I), only 3% to 4% of patients with insulinomas have other endocrine neoplasms. Insulinomas in patients with MEN I are usually single tumors that usually can be cured with enucleation of the tumor. In contradistinction, gastrinomas in patients with MEN I are diffuse in nature and resection only rarely can be accomplished. Long-term management of gastric hypersecretion is best accomplished by H2-receptor antagonists. If the patient does not respond to H2-receptor antagonists or is unwilling to take the drug indefinitely, he or she will be a candidate for total gastrectomy. PMID- 2884985 TI - Genetic differentiation of Murray Valley encephalitis virus in Australia and Papua New Guinea. AB - The genetic relatedness of ten Murray Valley encephalitis virus (MVE) isolates from Australia has been examined by comparing HaeIII and TaqI restriction digest profiles of cDNA to virion RNA. The isolates were from the Murray Valley region of south-eastern Australia and from the Ord River region of Western Australia and spanned a period of 23 years (1951-1974). The isolates generated closely similar restriction digest profiles. The extent of similarity suggested that the level of nucleotide sequence divergence between any pair of Australian MVE isolates is probably around 1%. The genetic homogeneity of the MVE isolates contrasts with results obtained for Ross River virus, an alphavirus, using an identical methodological approach; we propose that this difference results from the important role of birds in the life cycle of MVE. Four MVE isolates from three fatal human cases showed small genetic differences one from the other. These isolates did not have a common restriction digest profile which distinguished them from strains obtained from other sources (e.g., from mosquitoes or a heron). The data do not support the view that clinical cases of MVE infection in humans are due to a particular strain of virus although this has not been rigorously excluded. The two available MVE isolates from Papua New Guinea (PNG) were from the Sepik and Port Moresby regions. They generated HaeIII and TaqI restriction digest profiles which were different both from each other and from those of the Australian type. Genetic divergence between the two PNG isolates was estimated to be approximately 6%; divergence between either of the PNG isolates and the Australian type was greater than 6%. Our data suggest that the evolution of MVE in Australia and PNG has proceeded independently and that circulating Australian MVE strains are not systematically re-seeded from regions of endemicity in PNG. Studies on the relatedness of MVE and two close antigenic relatives, Japanese encephalitis virus (JE) and Alfuy virus (ALF), showed that the genetic relatedness between any MVE isolate and JE or ALF is less than that between the most divergent of the MVE isolates, including those from Papua New Guinea. PMID- 2884986 TI - Is incomplete fear-reduction followed by a return of fear? PMID- 2884987 TI - Tyrosine hydroxylase-immunoreactive neurons in the hypothalamus of the crested newt. An electron microscopic study. AB - The fine structure and specialized neuronal, vascular and ventricular relations of tyrosine hydroxylase (TH)-immunopositive neurons and processes were examined in the hypothalamus of the crested newt. TH-immunoreactive neurons form a well developed system. Its possible role in the hypothalamic neuroendocrine mechanisms is discussed. PMID- 2884988 TI - The effects of negative chronotropic interventions on sinus node recovery time. AB - The effects of multiple increases in sinus cycle length on sinus node recovery time (SNRT) were examined in 5 dogs. Pacing was performed from the left atrial appendage for 30 and 60 seconds using at least 4 different pacing cycle lengths selected between 230 and 620 msec. Each dog received propranolol (1 mg/kg, IV) prior to any measurements. The effects of increases in sinus cycle length on SNRT were first assessed during 2 levels (4 and 8 Hz) of continuous vagal stimulation. From a control cycle length of 439 +/- 28 msec (mean +/- SE), the vagal stimulations lengthened the sinus cycle lengths to 604 +/- 10 msec and 758 +/- 16 msec respectively. Sinus cycle length was then prolonged by combined muscarinic and beta-receptor blockade resulting in a sinus cycle length of 549 +/- 9 msec. Autonomic blockade plus verapamil (3-10 mg IV) resulted in sinus cycle lengths of 612 +/- 14 and 721 +/- 18 msec respectively, which were not significantly different from those obtained with vagal stimulation. Data relating SNRT to the sinus cycle length, pacing cycle length, duration of pacing and the negative chronotropic interventions used to achieve the changes in the sinus cycle length were analyzed via covariance analysis. The results demonstrate that the single most important determinant of SNRT is the sinus cycle length. Furthermore, equivalent increases in sinus cycle length whether obtained by vagal stimulation, autonomic blockade or intravenous verapamil results in SNRTs that are not significantly different. Therefore, in the sinus node, changes in the rate of pacemaker activity, regardless of how they are achieved, will largely determine the changes in SNRT. PMID- 2884989 TI - Metabolic fate of glutamate carbon in rat renal tubules. Studies with 13C nuclear magnetic resonance and gas chromatography-mass spectrometry. AB - 13C-n.m.r. spectroscopy and g.c.-m.s. were used to determine the metabolic fate of glutamate carbon in rat kidney. The main purpose was to characterize the effect of chronic metabolic acidosis on the utilization of glutamate carbon. Renal tubules obtained from normal and chronically acidotic rats were incubated in Krebs buffer, pH 7.4, in the presence of 2.5 mM-[3-13C]glutamate. During the course of incubation the concentrations of total glucose and NH3 were significantly (P less than 0.05) higher in tissue from acidotic rats. The levels of some tricarboxylic-acid-cycle intermediates were higher (P less than 0.05) in control tissue. In control tissue, 13C-n.m.r. spectra demonstrated a significantly higher rate of 13C appearance of aspartate, glutamine and [2,4 13C]glutamate. However, in acidosis the resonances of [13C]glucose carbon atoms were significantly higher. In the control, approx. 15% of glutamate carbon was accounted for by [13C]glucose formation as against 30% in chronic acidosis. However, in control tissue, 44% of glutamate carbon utilization was accounted for by recycling to glutamate and formation of aspartate, glutamine and GABA. In acidosis, only 11% was so recovered. Analysis of 15NH3 formation during the course of incubation with 2.5 mM-[15N]glutamate demonstrated a positive association between the appearance of [13C]glucose and 15NH3 both in the control and in acidosis. The data suggest that the control of gluconeogenesis and ammoniagenesis in acidosis is, in part, referable to a diminution in the rate of the reductive amination of alpha-oxoglutarate, that of the transamination reaction and that of glutamine synthesis. PMID- 2884991 TI - Use of rapid gel-permeation chromatography to explore the inter-relationships between polymerization, phosphorylation and activity of acetyl-CoA carboxylase. Effects of insulin and phosphorylation by cyclic AMP-dependent protein kinase. AB - Superose 6 chromatography was used to separate rapidly the polymeric and dimeric forms of acetyl-CoA carboxylase. With preparations of acetyl-CoA carboxylase purified by Sepharose-avidin chromatography, it is shown that citrate promotes polymerization and that the extent of polymerization is diminished, but not eliminated, after phosphorylation by cyclic-AMP-dependent protein kinase. After exposure of rat epididymal adipose tissue to insulin, evidence was obtained for a marked increase in polymerization. The polymeric form, which was active in the absence of citrate, exhibited increased phosphorylation, particularly on a tryptic peptide designated the I-peptide in an earlier study [Brownsey & Denton (1982) Biochem. J. 202, 77-86]. In contrast, in tissue exposed to the beta agonist isoprenaline, most of the phosphorylated acetyl-CoA carboxylase appeared to be in the dimeric form if chromatography was carried out in the absence of citrate, whereas in the presence of citrate the degree of polymerization was diminished. PMID- 2884992 TI - Investigation of the role of Ca2+ and calmodulin in the regulation of platelet guanylate cyclase activity. AB - Both soluble and particulate forms of human platelet guanylate cyclase were found to be sensitive to sub-micromolar concentrations of free Ca2+; soluble enzyme activity increased as Ca2+ was increased from 10 nM to 1 microM; particulate enzyme activity showed a biphasic response to Ca2+, with maximal enzyme activity between 1 and 10 nM free Ca2+ and inhibition occurring at higher Ca2+ concentrations. Neither Ca2+-sensitivity appeared to be calmodulin-dependent. PMID- 2884994 TI - Association of the atrial natriuretic factor receptor with guanylate cyclase in solubilized rat glomerular membranes. AB - The elution profile of solubilized rat glomerular membranes from a gel filtration column showed two peaks of 125I-ANF (atrial natriuretic factor) binding (367 +/- 21, 156 +/- 12 KDa). Over 85% of the total binding for the extract was in the 367 KDa peak. Guanylate cyclase activity was correlated with 125I-ANF specific binding. ANF activation of guanylate cyclase was also observed. As observed previously with particulate membrane, Scatchard-analysis of ANF binding data with the solubilized extract was consistent with a two-site model. Both affinities (Kd's), 4 pM and 1 nM, are within the range of blood concentrations reported for ANF. These observations suggest that most rat glomerular ANF receptors are large molecular complexes coupled with guanylate cyclase in the 300-350 KDa size range. PMID- 2884990 TI - Protein phosphorylation in rat mammary acini and in cytosol preparations in vitro. Phosphorylation of acetyl-CoA carboxylase is unaffected by cyclic AMP. AB - Phosphorylation of soluble proteins in rat mammary acinar cells was investigated. When phosphorylation proceeded in intact cells, in the presence of [32P]Pi, the major non-casein phosphoproteins, including acetyl-CoA carboxylase, were unresponsive to incubation conditions that caused major increases in the intracellular concentration of cyclic AMP. The overall 32P specific radioactivity (c.p.m./microgram of protein) of acetyl-CoA carboxylase, assessed after affinity purification of the enzyme with avidin-Sepharose, was unchanged by incubation under such conditions. Furthermore, the distribution of 32P among tryptic phosphopeptides of the enzyme, resolved by reversed-phase h.p.l.c., was not altered by cyclic AMP-increasing treatments of the acinar cells. When cytosol fractions were incubated with [gamma-32P]ATP, some phosphoproteins responded to the addition of micromolar concentrations of dibutyryl cyclic AMP or cyclic AMP by undergoing an enhancement of phosphate incorporation. In these experiments in vitro, protein phosphatase activity did not make a major contribution to the net phosphorylation of individual phosphoproteins, and acetyl-CoA carboxylase was not prominent among the phosphoproteins identified after short (less than 1 min) incubations of cytosols with [gamma-32P]ATP. The resistance of protein phosphorylation to variations in the cyclic AMP concentration in intact mammary epithelial cells, demonstrated by this work, is one of several mechanisms that ensure the pleiotropic refractoriness of those cells to agents which normally cause a stimulation of adenylate cyclase activity in hormone-sensitive cells. PMID- 2884995 TI - Changes in the beta-subunit of mitochondrial F1 ATPase during neurogenesis. AB - A polypeptide migrating in the area of the isotubulin in 2 D-gel electrophoresis of extracts from neuronal cells was characterized as the beta-subunit of the F1 ATPase matrix component. The synthesis of this subunit is enhanced during neurogenesis and the presence of an isoform was detected in adult mouse brain. PMID- 2884993 TI - Insulin activation of lipogenesis in isolated mammary acini from lactating rats fed on a high-fat diet. Evidence that acetyl-CoA carboxylase is a site of action. AB - Feeding lactating rats on high-fat cheese crackers in addition to laboratory chow increased the dietary intake of fat from 2 to 20% of the total weight of food eaten and decreased mammary-gland lipogenesis in vivo by approx. 50%. This lipogenic inhibition was also observed in isolated mammary acini, where it was accompanied by decreased glucose uptake. These inhibitions were completely reversed by incubation with insulin. Insulin had no effect on the rate of glucose transport into acini, nor on pyruvate dehydrogenase activity as estimated by the accumulation of pyruvate and lactate, suggesting that these are not the sites of lipogenic inhibition. Insulin stimulated the incorporation of [1-14C]acetate into lipid in acini from high-fat-fed rats. In the presence of alpha cyanohydroxycinnamate, a potent inhibitor of mitochondrial pyruvate transport, and with glucose as the sole substrate, neither [1-14C]glucose incorporation into lipid nor glucose uptake were stimulated by insulin. Insulin did stimulate the incorporation of [1-14C]acetate into lipid in the presence of alpha cyanohydroxycinnamate, and this was accompanied by an increase in glucose uptake by the acini. This indicated that increased glucose uptake was secondary to the stimulation of lipogenesis by insulin, which therefore must occur via activation of a step in the pathway distal to mitochondrial pyruvate transport. Insulin stimulated acetyl-CoA carboxylase activity measured in crude extracts of acini from high-fat-fed rats, restoring it to values close to those of chow-fed controls. The effects of insulin on acetyl-CoA carboxylase activity and lipogenesis were not antagonized by adrenaline or dibutyryl cyclic AMP. PMID- 2884996 TI - Phosphorylated isomers of L-dopa stimulate MSH binding capacity and responsiveness to MSH in cultured melanoma cells. AB - L-dopa is a key metabolite in the process of melanogenesis. However, it is difficult to use in biological experiments because it is subject to auto oxidation and relatively insoluble at neutral pH. Dopa phosphates contain phosphate ester linkages at positions 3 and/or 4 of the phenylalanine ring of L dopa, rendering them highly soluble and stable to auto-oxidation when compared to L-dopa. Dopa phosphates are readily taken up by melanoma cells in culture and converted to L-dopa and inorganic phosphate by cellular phosphatases, making them useful for studying L-dopa effects in vivo. Here we investigated the effects of dopa phosphates on receptors for MSH in cultured melanoma cells. We found that dopa phosphates caused a 3-fold stimulation of MSH binding capacity by the cells which probably occurred through an increase in the number of receptors for MSH with no apparent change in affinity of the receptors. The increased binding capacity for MSH was followed by increased cellular tyrosinase activity and melanogenesis. Thus dopa phosphates and/or L-dopa can act as regulators of the MSH receptor system. The observations suggest a novel mechanism for regulation of hormonal responsiveness: hormonal signal amplification by a metabolite in the target pathway. PMID- 2884997 TI - Prostaglandin E1 binding protein on the surface of primary cultured hepatocytes. AB - Prostaglandin E1 (PGE1) was bound to primary cultured rat hepatocytes in a receptor-dependent manner in serum-free medium at 4 degrees C. When added at a concentration of 2 X 10(-9) M, maximal specific binding occurred within 60-90 min. Trypsin treatment of the cells reduced the binding capacity to about 50% of that of untreated cells. Scatchard-analysis of the binding data showed that the cells had an apparent dissociation constant of 1.2 X 10(-8) M and a binding capacity of 580 fmol (approximately 3.5 X 10(11) PGE1 receptors)/mg of protein. In experiments at 37 degrees C, maximal specific binding occurred within 5 min and was 6-7 times that at 4 degrees C, but the amount of bound PGE1 decreased rapidly after 5 min due to metabolism of PGE1 in the hepatocytes. Thin-layer chromatographic analysis showed that the material bound to the cell surface consisted of intact PGE1 and its metabolites at 37 degrees C, but PGE1 only at 4 degrees C. PMID- 2884998 TI - Antipili antibody affords protection against ascending pyelonephritis in rat: evaluated by renal brush border membrane enzymes. AB - Kinetic parameters (Km and Vmax) of renal brush border membrane (BBM) enzymes alkaline phosphatase, maltase, leucine aminopeptidase and gamma glutamyltranspeptidase were worked out in control, infected and immunized infected rats. There was no significant change in the Km of all the enzymes studied in three groups. The Vmax of all the enzymes studied decreased significantly (p less than 0.05) 3 or 4 days postinfection and onwards in the left obstructed kidney of infected and immunised-infected animals. However, in the right unobstructed kidney the Vmax of alkaline phosphatase and leucine aminopeptidase increased significantly (p less than 0.05) in the early stages and decreased (p less than 0.05) in later stages in both the experimental groups. The significant difference (p less than 0.05) in the Vmax of infected and immunized infected groups at various stages of infection revealed the partial protective role of antipili antibody against ascending pyelonephritis. PMID- 2885000 TI - Inhibition of microsomal biotransformation by a series of nitrogen and oxygen heterocyclic histamine H2-antagonists. AB - A homologous series of potent, long-lasting thiazolo-pyrimidone-pyridine histamine H2-antagonists were examined for their inhibitory effects on rat hepatic ethylmorphine N-demethylation. Inhibitory potency increased in the order: 2-pyridinyl less than 3-pyridinyl less than 4-pyridinyl histamine H2-antagonist. Substitution ortho to the pyridine nitrogen decreased inhibitory potency. Hydroxylation of the pyridine heterocycle decreased inhibitory potency, whereas substituent electronic effects did not appreciably alter the inhibitory potency of these compounds. Antagonists containing oxygen heterocycles were moderately potent inhibitors compared to those containing unsubstituted pyridine as the heterocycle. A 3-(6-methylpyridine) histamine H2-antagonist was shown to be a slightly more potent inhibitor of ethinamate metabolism than cimetidine in rats. However, unlike cimetidine, it did not inhibit the plasma half-life of antipyrine in dogs at doses that were equally efficacious in inhibiting gastric acid secretion. PMID- 2884999 TI - Partial deficiency of subunits in complex I or IV of patients with mitochondrial myopathies. AB - Subunits of Complexes I, III, IV, and V from skeletal muscle mitochondria isolated from four patients with mitochondrial myopathies were analyzed by immunoblotting. A deficiency was observed in Complex I or IV, or in both. The patterns of deficiency of subunits of each complex were similar both in patients with deficiency of a single complex and in patients with combined deficiency of the two complexes. The deficiency of any of these subunits was only partial, and no abnormalities in the electrophoretic mobilities of the subunits were observed. These results suggest that the deficiency of Complex I or IV in these patients are based on similar molecular defects which lead to decreased levels of these subunits. PMID- 2885001 TI - Lipophilic beta-adrenoceptor antagonists stimulate cholesterol biosynthesis in human skin fibroblasts. AB - The effect of a series of beta-adrenoceptor antagonists on cholesterol biosynthesis was studied in vitro in normal human skin fibroblasts. Some, but not all, of the drugs studied stimulated the incorporation of [2-14C]-acetate into cell sterols in a dose-dependent manner. This effect was unrelated to beta blocking potency, selectivity for beta 1 or beta 2 adrenoceptors and partial agonistic activity of the drugs, thus ruling out a beta-receptor mediated mechanism. A positive, statistically significant correlation was found, however, between the drug lipophilicity and the stimulation of sterol biosynthesis. Propranolol, the most effective agent in increasing [2-14C]-acetate incorporation into cellular sterols, also enhanced the conversion of 3-hydroxy-3-methylglutaryl CoA (HMGCoA) into mevalonic acid, suggesting an interference of lipophilic beta adrenoceptor antagonists with HMHCoA-reductase, the feed-back regulated rate limiting step of cholesterol biosynthesis. PMID- 2885002 TI - Effects of long-term administration of clofibric acid on stearoyl-CoA desaturase, 1-acylglycerophosphorylcholine acyltransferase and fatty acyl composition of microsomal phosphatidylcholine in rat liver. AB - Long-term effects of p-chlorophenoxyisobutyric acid (clofibric acid) on inductions of stearoyl-CoA desaturase and 1-acylglycerophosphorylcholine (1-acyl GPC) acyltransferase, and on changes in fatty acyl composition of microsomal lipid in rat liver were studied. Male rats were fed clofibric acid at a dietary concentration of 0.25% for 2 or 22 weeks. Inductions of stearoyl-CoA desaturase and 1-acyl-GPC acyltransferase lasted throughout the long-term treatment and were the same as those of either young or aged rats which were treated with clofibric acid for 2 weeks. The long-term treatment of rats with clofibric acid scarcely affected components of stearoyl-CoA desaturation system other than terminal desaturase. In accordance with the induction of stearoyl-CoA desaturase, the increase in the proportion of octadecenoic acid in hepatic lipid lasted throughout the 22-week treatment. In the case of both of the long-term treatment and the short-term treatment of rats, the increase in the proportion of octadecenoic acid in microsomal phosphatidylcholine was due to the marked increase in the proportion of octadecenoic acid in position 2, but not position 1, of phosphatidylcholine. These changes in fatty acyl composition of phosphatidylcholine were not due to the alteration of the content of phosphatidylcholine in liver. PMID- 2885003 TI - Two distinct mechanisms for regulation of gamma-glutamyl transpeptidase in cultured rat hepatocytes by glucocorticoid-like steroids. AB - Adult rat hepatocytes maintained in primary monolayer culture with defined medium were used to characterise two effects of glucocorticoid-like steroids in regulating gamma-glutamyltranspeptidase (GGT). Low concentrations of glucocorticoids alone had little effect on GGT but synergistically enhanced induction of the enzyme by liver tumor-promoting xenobiotics such as 1,1,1 trichloro-2,2-bis-(4-chlorophenyl)-ethane (DDT) and hexachlorocyclohexane. The enhancing effect appears to be mediated by the classical glucocorticoid hormone receptor since structural requirements and concentration-dependence for enhancement were similar to those for induction of tyrosine aminotransferase in parallel cultures. Higher concentrations (1-100 microM) of various glucocorticoids alone increased GGT activity. Most glucocorticoids induced GGT but their order of potency did not parallel that for induction of tyrosine aminotransferase under similar culture conditions. Among the most potent glucocorticoids, triamcinolone was a weak GGT inducer and cortivazol appeared to act as an antagonist of GGT induction by steroids. Some non-glucocorticoids including pregnenolone 16 alpha-carbonitrile, and some progestins, also induced but required addition of 30 nM dexamethasone for maximal effect. Some specific steroid structural features were identified which increased (presence of a 16 alpha methyl group) or impaired GGT-inducing activity. Although interpretation is complicated by differential metabolism of individual steroids in culture, the results suggest that GGT induction by pharmacological levels of steroids may be mediated, directly or indirectly, by one or more relatively specific receptors distinct from the classical glucocorticoid receptor. PMID- 2885004 TI - Effect of decarboxylase inhibitors on brain p-tyrosine levels. AB - A number of inhibitors of L-aromatic amino acid decarboxylase (AAD) and monoamine oxidase (MAO) were tested to determine whether they also inhibited tyrosine aminotransferase (TAT). The AAD inhibitors carbidopa, NSD-1015, NSD-1034 and Ro4 5127 inhibited liver TAT. Carbidopa inhibited brain AAD and liver TAT equally well. In contrast, other AAD inhibitors (Ro4-4602 and alpha-monofluoromethyldopa) did not inhibit TAT. Phenelzine, an MAO inhibitor, inhibited liver TAT, but other MAO inhibitors (tranylcypromine and isocarboxazid) did not. Systemic administration of those drugs that were found to be inhibitors of TAT in vitro caused significant increases in rat brain p-tyrosine levels. PMID- 2885005 TI - Adult T cell leukemia-lymphoma mimicking rheumatic disease. PMID- 2885007 TI - Circadian phase dependency of the effects of different beta-receptor blocking drugs on motor activity of rats. Importance of drug lipophilicity. AB - The effects of seven beta-receptor blocking drugs differing in lipophilicity by 3.5 orders of magnitude (propranolol, bupranolol, oxprenolol, metoprolol, sotalol, practolol, atenolol) were studied on the circadian rhythm in motor activity of light-dark-synchronized (light (L): 7-19 h, dark (D): 19-7 h) male rats. Motor activity after i.p. injection of saline or of the racemic mixtures of all drugs and the isomers of propranolol, bupranolol and practolol was measured in groups of 5 rats with a motimeter. Two doses of either drug were injected either at 7:30 a.m. in L or at 7:30 p.m. in D. In L the drugs did either not affect motor activity or even increased motility in comparison to saline. No dosage-dependency was observed in the drug effects in L. In contrast, during D a dosage-dependent decrease in motor activity was found for all compounds. ED50 values of decrease in motility during D were negatively correlated with lipophilicity (partition coefficient) of the compounds. No significant difference was found in the ED50-values of the isomers studied. The results clearly demonstrate a circadian phase dependency in the effects of beta-receptor blocking drugs on motor activity of rats. A dosage-dependent central depressant effect of the drugs could be observed only in D. It is concluded that the central depressant effects of beta-receptor blocking drugs are mainly due to the non specific, lipophilic property of the drugs and not brought about by a specific blockade of central beta-adrenoceptors. PMID- 2885006 TI - [The spasmolytic activity of propiverine and some of its structural analogs]. AB - The spasmolytic activity of propiverine and its corresponding methyl ether analogue was investigated in the isolated ileum and urinary bladder of the rat. It could be demonstrated that the antispasmodic properties of propiverine were, in contrast to its methyl ether analogue, not only based on a blockade of muscarinic receptors but were also a consequence of nonspecific papaverine-like effects. Investigations with three putative metabolites showed that the alcohol derivative O-desalkylpropiverine was about two orders of magnitude more potent than propiverine itself in blocking spasmogenic effects of the agonist arecaidine propargyl ester. In contrast no spasmolytic effect could be observed after application of the corresponding carboxylic acids (benzilic acid propyl ether; benzilic acid 2-hydroxypropyl-ether. PMID- 2885008 TI - Blood plasma peptides of rats after administration of ethanol or acetaldehyde. AB - The blood plasma peptide fractions labelled with 3H-leucine after chronic administration of ethanol or acetaldehyde in rats have been analysed. Total 3H leucine radioactivity in peptide fraction calculated per millilitre of plasma in both study groups was significantly decreased. The amount of peptide spots obtained by tlc in the ethanol-treated group or acetaldehyde-treated group was reduced in comparison with the control group. Analysis of amino acid composition of atypical spots occurring in both test groups revealed the presence of aromatic amino acids and methionine, but was associated with the absence of branched-chain amino acids, such as valine, leucine and isoleucine. These findings suggest a change in protein metabolism in hepatic dysfunction in rats receiving ethanol or acetaldehyde. PMID- 2885009 TI - Serum ferritin as a marker of alcohol consumption in working men. AB - For 576 working men the relationship between reported recent alcohol consumption, serum ferritin, mean cell volume, and gamma glutamyl transferase was studied. Serum ferritin was significantly increased in heavy drinkers, but as a screening test it failed to yield a useful advantage over a combination of mean cell volume and gamma glutamyl transferase. PMID- 2885010 TI - [Strain and stress response on VDT performance]. PMID- 2885012 TI - [Treatment of acute asthma]. PMID- 2885011 TI - Structure and assembly of coated vesicles. PMID- 2885013 TI - Purification and kinetic properties of sialidase from Clostridium perfringens. AB - Clostridium perfringens sialidase was isolated from a culture medium of bacterial cells by ammonium sulfate precipitation (42-85%), followed by purification through Sephadex G-75 gel chromatography, DEAE A-50 anion exchange chromatography, FPLC medium pressure anion exchange chromatography and finally FPLC medium pressure isochromatofocussing. From 9 l culture medium 1.17 mg sialidase was isolated with a specific activity of 295 U/mg. The enzyme appeared to be homogeneous by analytical polyacrylamide gel electrophoresis. The molecular mass was measured to be 66 kDa. Km values ranging from 0.6 to 1.6mM were determined for several oligosaccharides as substrates. The enzyme catalyzed transglycosylation reactions with methanol as a nucleophilic reagent competitive with water. In the enzymatic hydrolysis of the (3'-methoxyphenyl)glycoside of alpha-N-acetylneuraminic acid, increase of methanol concentration had no effect on the release of 3-methoxyphenol. This finding suggests that the formation of the enzyme-glycon intermediate is the rate-determining step for this substrate. PMID- 2885014 TI - The role of chromosomal translocations in B- and T-cell neoplasia. PMID- 2885015 TI - Recent advances in the molecular biology of HTLV-1: trans-activation of viral and cellular genes. PMID- 2885016 TI - Lymphocyte hormone receptors. PMID- 2885017 TI - Differential diagnosis between mesotheliomas and metastatic adenocarcinomas using monoclonal antibodies against gastrointestinal carcinoma antigen and stage specific embryonic antigen. AB - Monoclonal antibodies made against gastrointestinal carcinoma antigen (GICA) and stage specific embryonic antigen (SSEA) were evaluated for their ability to distinguish normal mesothelial cells present in pleural and peritoneal fluids from adenocarcinoma cells in tissue and cytology specimens. The presence of GICA was documented in a high percentage of adenocarcinomas from the gastrointestinal tract (75/98) and in 52% of pulmonary (15/29) and 29% of ovarian (6/21) adenocarcinomas. GICA was found infrequently in breast carcinoma (1/18) and not in mesotheliomas (0/16). A similar pattern of GICA expression was seen in malignant effusions from adenocarcinomas (18/47) and mesotheliomas (0/6). SSEA was found in a high percentage of adenocarcinomas derived from the gastrointestinal tract (47/56) and the lung (26/29). SSEA was detected in breast carcinoma (8/15) more often than GICA. SSEA was detected rarely in mesotheliomas (1/16). Reactivities for epithelial membrane antigen, keratin, carcinoembryonic antigen, GICA and SSEA in adenocarcinoma and mesotheliomas were compared. PMID- 2885018 TI - The role of phospholipase in beta-agonist-induced down regulation in guinea pig lungs. AB - It has been observed that repeated and prolonged beta-agonist treatment causes the impairment of beta-adrenergic function, so-called "desensitization" or "down regulation". To clarify the mechanism of down regulation, the following experiment was performed using guinea pig lungs. Animals were divided into four groups: In the metaproterenol groups, guinea pigs were treated with metaproterenol (10 mg/kg/day) by intraperitoneal injection once a day for 1 day or for 7 successive days In the control groups, guinea pigs were treated with saline by the same procedure as in the metaproterenol groups. In the group treated with metaproterenol for 7 days, there was a 45% reduction in the number of beta-adrenoceptors and a 62% reduction in adenylate cyclase activity, compared with those of the control group. However, there were no significant changes in the dissociation constant (Kd) of the receptors. On the other hand, no reduction in the number of beta-adrenoceptors and adenylate cyclase activity was observed in the group treated with metaproterenol once a day for 1 day, compared with those of the control group. Phospholipase (PLase) activity in the lung microsomes of guinea pigs injected with metaproterenol for 1 day and for 7 days was elevated by 14.4 and 33.1%, respectively, compared with that of the control groups. Phospholipid contents of lung membranes prepared from the animals treated with metaproterenol for 7 days were significantly decreased compared with those of the control group, though in the group treated with metaproterenol once a day for 1 day, phospholipid contents did not differ from those of the control. Lung membranes treated with PLase A2 revealed decreases both in the number of beta adrenoceptors and adenylate cyclase activity, dose dependently. These results and the fact that membrane phospholipids are involved in the beta-adrenoceptor system suggest that down regulation observed during beta-agonist administration is, at least in part, attributed to degradation of phospholipids of lung membranes by the persistent activation of PLase in the tissue. PMID- 2885019 TI - The anti-inflammatory activity of Enicostemma littorale and Mollugo cerviana. AB - The anti-inflammatory activity of E. littorale and M. cerviana was assessed by carrageenan-induced inflammation and cotton pellet granuloma method in rats. E. littorale and M. cerviana exerted 54 and 26% anti-inflammatory activity for a dose of 100 mg/100 g body wt, respectively, in carrageenan-induced acute inflammation. In chronic inflammation of cotton pellet granuloma, E. littorale and M. cerviana exerted 30 and 46% anti-inflammatory activity at the above dosage, respectively. The optimal dose for these drugs was determined in carrageenan inflammation. The effect of the alcoholic extract of these drugs on human erythrocyte membrane stabilization and inhibition of cobra venom phospholipase A2 was studied in vitro and the drugs were found to be effective. Further, these drugs were found to inhibit the levels of lipid peroxides, acid phosphatase, and gamma-glutamyl transpeptidase activity in the exudate of cotton pellet granuloma. The effects were compared with those of standard anti inflammatory drug, hydrocortisone. A possible mode of action of these drugs is suggested. PMID- 2885020 TI - The use of benzodiazepines among drug addicts. PMID- 2885021 TI - Group treatment of benzodiazepine dependence. PMID- 2885024 TI - Increased activity of serum amine oxidases in granuloma annulare, necrobiosis lipoidica and diabetes. AB - Serum monoamine oxidase, diamine oxidase and lysyl oxidase-like activity were measured in patients with granuloma annulare (GA), necrobiosis lipoidica (NL) and diabetes mellitus. In diabetes, all enzyme measurements were raised by a factor of about 2 X 2, and in NL by a factor of about 1 X 5. The rise in patients with GA was small and only significant in the case of benzylamine monoamine oxidase. "Stiff' collagen would seem to link these three disorders and the present results suggest that these amine oxidases could be useful in monitoring collagen abnormality in diabetes and diabetes-associated disorders, particularly in the absence of chronic liver disease. A negative correlation was found between enzyme activity and blood glucose levels, thus collagen changes in these conditions may occur independently of elevated blood glucose levels. Possible involvement of these enzymes in angiopathy remains to be elucidated. PMID- 2885023 TI - Effect of rifampicin on haem and bilirubin metabolism in man. AB - Haem and bilirubin metabolism was studied in seven healthy volunteers during 4 weeks treatment with rifampicin 600 mg at night. The serum unconjugated bilirubin concentration increased 2-3 fold in the first 24 h of treatment (P less than 0.01) and subsequently fell to below pretreatment values (P less than 0.05) during the third and fourth weeks of rifampicin therapy. In each subject, the activity in leucocytes of delta-aminolaevulinic acid (ALA) synthase increased and that of protoporphyrinogen (proto) oxidase decreased during the first week of therapy. The mean ALA synthase activity was most markedly increased on day 4 being seven-fold its pretreatment value (P less than 0.01), and the mean proto oxidase activity most depressed on day 2 at 50% its pretreatment value (P less than 0.02). There was increased urinary excretion of porphobilinogen (PBG) during the first week of therapy and increased excretion of porphyrins and PBG during the third week of treatment. The increase in ALA synthase activity and haem precursor excretion can be explained by the combination of increased haem demand for haemoprotein induction and partial block in haem synthesis due to reduced proto oxidase activity. PMID- 2885022 TI - Adimolol, a long acting beta-adrenoceptor blocker in man. AB - A comparative study in eight healthy normotensive males of the effects on blood pressure, heart rate and beta-adrenoceptor function following single oral doses of adimolol (600 mg), propranolol (240 mg) and placebo. Both active treatments produced small but significant reductions in blood pressure and heart rate, supine and erect. These effects persisted for up to 7 days after adimolol. The heart rate increases following both dynamic exercise and intravenous isoprenaline were attenuated by both propranolol and adimolol. With adimolol evidence of functional beta-adrenoceptor antagonism was sustained for up to 7 days. Lymphocyte beta-adrenoceptor binding studies showed that both adimolol and propranolol significantly reduced affinity for beta-adrenoceptors. In addition, adimolol significantly reduced receptor number and even by 3 days after dosing Bmax had only returned to half the control value. In a small sub-group of subjects there was no evidence to suggest that adimolol had additional alpha adrenoceptor antagonist properties. Adimolol was detected in plasma for up to 3 days after dosing. The mean terminal elimination half-life was 14 h, compared to 3 h for propranolol. This study confirms that adimolol has prolonged beta adrenoceptor antagonist activity with effects persisting for up to 7 days after a single dose. The reduction in beta-adrenoceptor number following adimolol suggests that this prolonged effect may not be solely due to competitive antagonism but may additionally depend upon non-competitive antagonism at beta adrenoceptors. PMID- 2885025 TI - Peripheral blood stem cell autografts in the treatment of lymphoid malignancies: initial experience in three patients. AB - Large numbers of circulating haemopoietic progenitor cells were collected from three patients with lymphoid neoplasms for the purpose of haemopoietic reconstitution following intensive chemotherapy or chemoradiotherapy. Each patient underwent four to six leukaphereses at a time when the circulating stem cell pool was expanded. 2-3 weeks after the end of myelosuppressive chemotherapy. The peripheral blood mononuclear cells (PBMNC) thus obtained were assayed for granulocyte-macrophage colony-forming cells (CFU-GM) and were cryopreserved in liquid nitrogen. Two patients were autografted with PBMNC containing 60 X 10(4) and 76 X 10(4) CFU-GM/kg body weight respectively. Both these patients showed prompt engraftment which is stable at +10 and +6 months. A third patient who was autografted with PBMNC containing 33 X 10(4) CFU-GM showed only temporary and incomplete engraftment. These observations confirm that the peripheral blood may be used as a source of haemopoietic stem cells for autografting, but criteria for predicting engraftment are at present uncertain. PMID- 2885026 TI - Characteristics of the formation of enzyme-bound ATP from medium inorganic phosphate by mitochondrial F1 adenosinetriphosphatase in the presence of dimethyl sulfoxide. AB - Addition of dimethyl sulfoxide promotes the formation of enzyme-bound ATP from medium Pi by mitochondrial F1 adenosinetriphosphatase that has tightly bound ADP present. Measurements are reported of medium Pi in equilibrium H18OH exchange and of the dependence of formation of enzyme-bound ATP on Pi concentration. Attainment of an apparent equilibrium between medium Pi and bound ATP requires longer than 30 min, even though the rates of Pi binding and release after apparent equilibrium is reached would suffice for a faster approach to equilibrium. Slow protein conformational changes or other unknown modulating factors may be responsible for the slow rate of bound ATP formation. After apparent equilibrium is reached, each Pi that binds to the enzyme reversibly forms ATP about 50 times before being released to the medium. The rate of interconversion of bound ATP to bound ADP and Pi is much slower than that in the absence of dimethyl sulfoxide as measured with sufficiently low ATP concentrations so that single-site catalysis is favored. Although the interconversion rate is slowed, the equilibrium constant for bound ATP formation from bound ADP and Pi is not far from unity. Dimethyl sulfoxide favors the formation of enzyme-bound ATP by promoting the competent binding of Pi to enzyme with ADP bound at a catalytic site rather than by promoting formation of bound ATP from bound ADP and Pi. PMID- 2885027 TI - Identification of methionine-110 as the residue covalently modified in the electrophilic inactivation of D-amino-acid oxidase by O-(2,4-dinitrophenyl) hydroxylamine. AB - The reaction of O-(2,4-dinitrophenyl)hydroxylamine with D-amino-acid oxidase leads to complete inactivation which can be protected against by the competitive inhibitor benzoate [D'Silva, C., Williams, C. H., Jr., & Massey, V. (1986) Biochemistry 25, 5602-5608]. The residue modified has been identified as methionine-110. Differential high-performance liquid chromatography mapping of tryptic digests of D-amino-acid oxidase modified in the absence and presence of benzoate allows the isolation of a single methionine-containing tryptic peptide corresponding to residues 100-115 and referred to as T6-T7. In unmodified enzyme, the bond involving Arg-108 is readily cleaved and T6 and T7 are isolated. Brief treatment of peptide T6-T7 with carboxypeptidase Y released residues 112-115, and the residual peptide was isolated in good yield. Further treatment of this peptide (residues 100-111) with carboxypeptidase Y released Val and an unknown amino acid that comigrated with synthetically prepared S-aminomethionine sulfonium salt. The unknown compound and S-aminomethionine break down to methionine on treatment with dithiothreitol. PMID- 2885028 TI - Inactivation of the mitochondrial ATPase inhibitor protein by chemical modification with diethylpyrocarbonate. AB - Modification of histidine residue(s) by diethylpyrocarbonate treatment of submitochondrial particles obtained by sonication results in inhibition of ATPase activity and stimulation of oligomycin-sensitive H+ conduction. The inhibition of the ATPase (EC 3.6.1.3) activity persisted in F1 isolated from diethylpyrocarbonate-treated submitochondrial particles, which exhibited the absorbance spectrum of modified histidine. Thus the inhibition of the ATPase activity results from histidine modification in F1 subunits. Removal of the natural inhibitor protein from submitochondrial particles resulted in stimulation of proton conduction. After removal of F1 inhibitor protein from the particles the stimulatory effect exerted by diethylpyrocarbonate treatment on proton conduction was lost. Reconstitution experiments showed that purified F1 inhibitor protein lost, after histidine modification, its capacity to inhibit the ATPase activity and proton conduction. These observations show that the stimulation of proton conduction by the ATPase complex effected by diethylpyrocarbonate treatment results from histidine modification in F1 inhibitor protein. PMID- 2885029 TI - Expression of the HTLV-1 genome and its association with a unique T-cell malignancy. PMID- 2885030 TI - Nature of the interactions involved in the lipid-protein complexes of the Escherichia coli N-acetylmuramoyl-L-alanine amidase. AB - Depending on its concentration, phosphatidylglycerol, one of the three main Escherichia coli phospholipid species, is able to activate or inactivate the E. coli murein amidase (N-acetylmuramoyl-L-alanine amidase, EC 3.5.1.28) (Vanderwinkel, E. and De Vlieghere, M. (1985) Biochim. Biophys. Acta 838, 54-59). The mechanisms underlying the modulation of this enzyme activity were studied by analyzing the effects of cations, polycationic molecules, various surfactants and amphiphilic water-soluble compounds. K+, Mg2+ and polyamines were all able to prevent completely the enzyme inactivation produced by millimolar order concentration of phosphatidylglycerol. The efficiencies of the ionic species tested were in the order K+ less than Mg2+ = putrescine less than spermidine less than spermine. The kinetics of the counteraction processes were all sigmoidal. By contrast, the activation of the murein amidase produced by phosphatidylglycerol in micromolar concentration appeared to be insensitive to the ionic strength of the medium. Surfactants and amphiphilic molecules differing in their polar head and hydrophobic tail were found to activate the enzyme at various degrees for concentrations below their critical micellar concentration. The non-ionic surfactants were the most potent activators and remarkably mimicked the phosphatidylglycerol activation. The enzyme activation process appeared to require only a hydrophobic solvation shell around the protein. All kinetic data supported our previous interpretation of the phosphatidylglycerol-enzyme interactions in terms of multisite non-allosteric theory. PMID- 2885031 TI - Effects of amino-acid composition of the medium and addition of fatty-acid derivatives on the induction of lipogenic enzymes in cultured hepatocytes. AB - Effects of essential and non-essential amino acids on induction of lipogenic enzymes were investigated in cultured rat hepatocytes. Glucose-6-phosphate dehydrogenase was markedly induced by the addition of essential amino acids alone to the cultured medium, but was not induced by non-essential amino acids. Fatty acid synthetase was also markedly induced by a combination of both amino-acid types (more than by either type of amino acid alone). However, acetyl-CoA carboxylase and malic enzyme were slightly induced by the addition of essential and/or non-essential amino acids. When various kinds of fatty acids were individually added to the medium, the lipid-dependent decreases in lipogenic enzyme inductions were in the following order: 18:2 greater than 20:4 greater than 18:1 greater than 16:0. When either linoleic acid, linoleoyl-CoA or trilinolein was added to the medium, linoleic acid was more effective as an inhibitor of the induction, without impairing the viability of cells. PMID- 2885032 TI - Rapid purification of dipeptidyl peptidase IV from rat liver plasma membrane. AB - Dipeptidyl peptidase IV (EC 3.4.14.5) was solubilized from rat liver plasma membranes with sulphobetaine 14 and purified by successive affinity chromatography on Con A-Sepharose, wheat germ lectin-Sepharose and arginine Sepharose columns. The specific activity of the final preparation was 49.4 mumol Gly-Pro p-nitroanilide/min per mg protein, representing a 1098-fold purification of the homogenate. SDS-polyacrylamide gel electrophoresis of the arginine Sepharose eluate showed a single protein band with a molecular weight of 105,000. The isoelectric point was determined to be 3.9 under non-denaturing conditions with sulphobetaine 14. The preparation was free of post-proline cleaving enzyme. The content of aminopeptidase M was 0.2% of the total protein. PMID- 2885033 TI - A new class of soluble basic protein precursors of the cornified envelope of mammalian epidermis. AB - The cornified envelope has been shown to be formed beneath the plasma membrane as a result of the cross-linking of soluble and membrane-associated precursor proteins by transglutaminase. We have obtained a monoclonal antibody which reacts with the periphery of cells in the upper layers of human epidermis by indirect immunofluorescence (IIF) following immunization of mice with cornified envelopes of cultured human keratinocytes. The antibody also stained the cell peripheries of bovine, rat and mouse epidermis as well as stratified epithelium. Neutral buffer extracts of human cultured keratinocytes and epidermis examined under denaturing conditions contained polypeptides of molecular weight 14,900 and 16,800 which reacted with the antibody, and an additional component of molecular weight 24,800 was found in cultured cells. The polypeptides were shown to have a pI of about 9.0. Under non-denaturing conditions the two lower-molecular-weight polypeptides had an apparent molecular weight of 30,000, while the 24,800 protein had one of 60,000. Incubation of the polypeptides under conditions that activate transglutaminase resulted in a disappearance of the polypeptides or the formation of cross-linked products. Basic polypeptides with somewhat different pI values and molecular weights were identified in neutral buffer extracts of bovine and rat epidermis. The HCE-2 antibody appears to identify a new class of basic protein precursors of mammalian cornified envelope. PMID- 2885034 TI - Structural dynamics within mixed populations of microtubules and protofilament ribbons. AB - In the presence of glycerol, microtubule proteins reassemble into both microtubules and protofilament ribbons with C- and S-shaped cross-section profiles. By means of electron micrographs of cross-sectioned assemblies, we have demonstrated that, during the steady state, the percentage of ribbons, especially of C-shaped ones, decreases in favour of the formation of microtubules. The following conversion modes are discussed: A, closure of the protofilament wall by increasing its curvature; B, lateral association of C-ribbons; C, completion of C ribbons to microtubules by lateral association of tubulin; D, disassembly of ribbons and elongation of microtubules. We conclude that ribbon disassembly proceeding in an end-wise fashion and microtubule elongation is the favoured mode of conversion. Microtubule-associated proteins were found to be required for the steady-state conversions of ribbons into microtubules. In the absence of microtubule-associated proteins, C-ribbons associate laterally, forming S ribbons. It is shown that the protofilaments of the counter-curved parts of S ribbons have the same polarity. PMID- 2885036 TI - Role of catecholamines in the control of newborn kidney adenine nucleotide content. AB - During the 1st h of extrauterine life, the adenine nucleotide content of the rat kidney is modified: the ATP level increases (+30%) while ADP and AMP are lowered (-30 and -50%, respectively). This leads to a high value of energy charge in the newborn kidney (0.89 vs. 0.80 in the fetus). It was possible to obtain in utero a similar modification of ATP, ADP, AMP concentrations by injections to the fetuses of cAMP, dibutyryl cAMP, or isoprenaline. Conversely, the postnatal changes in adenine nucleotide content could be prevented by administration to the fetus, just before birth, of beta- or beta 1-adrenoreceptor antagonists. Therefore the rise of kidney energy charge following parturition appears to be under hormonal control. Glucagon had no effect on kidney adenine nucleotide content. It is strongly suggested that the catecholamines released at the time of parturition are the triggering factor of this evolution. PMID- 2885035 TI - [Regulation by catecholamines and cAMP of enzymes of thiol and disulfide metabolism]. AB - In vivo exo- and endogenous catecholamines have no influence on the activities of thioredoxin reductase, glutathione reductase, thiol transferase and nonselenium dependent glutathione peroxidase. At the same time catecholamines activate via beta-adrenoceptors glutathione S-transferase and selenium-dependent glutathione peroxidase from many tissues and inhibit gamma-glutamyl transferase from kidney. In vitro cAMP has identical effects on the activities of the above enzymes. The possible significance of regulation of glutathione metabolism enzymes is discussed. PMID- 2885037 TI - Performance of chronic schizophrenics on matched word and design recall tasks. AB - Matched word and design recall tasks were constructed and used to assess the performance of chronic schizophrenics on neuroleptics alone and on both neuroleptic and anticholinergic drugs. The two groups of patients performed at an equally low level on both tasks, without evidence for a differential deficit. The tasks did, however, evoke a differential deficit in clustering performance for designs as opposed to words. Although clustering, which is based on recall, is not necessarily as well matched for words and designs as recall itself, this result suggests a lateralized dysfunction in brain structures related to use of mnemonic organization at retrieval. PMID- 2885038 TI - Is plasma GABA of peripheral origin? AB - Plasma levels of gamma-aminobutyric acid (GABA) appear to be altered in affective disorders and alcoholism. Plasma levels of GABA were not affected by menstrual cycle, exercise, gender, gut flora, nor by cholinergic stimulation by bethanechol. An obvious peripheral source for plasma GABA could not be demonstrated. PMID- 2885040 TI - The effect of spermatogenic disruption on the ability of testicular fluid to stimulate androgen production by normal Leydig cells. AB - Reports from this and other laboratories have concluded that unilateral disruption of spermatogenesis induces a predominantly ipsilateral increase in the responsiveness of Leydig cells to stimulation with luteinizing hormone (LH) and have suggested that if such effects were mediated by locally produced hormones then such "factors" should be detectable in testicular interstitial fluid. We sought to demonstrate such factors in testicular fluid from gonads subjected to a variety of treatments that disrupt gametogenesis. Fluid (TF) was drained from testes of adult rats that had been sham treated, irradiated, or treated with busulfan in utero, made unilaterally or bilaterally cryptorchid, or were unilaterally or bilaterally efferent-duct-ligated. Leydig cells obtained from normal rats basally produced 8 +/- 1 ng androgen/10(6) Leydig cells/2 h and, when maximally stimulated with LH, produced 66 +/- 3 ng. The addition of the various TFs to the incubations significantly increased both basal and LH-stimulated androgen production. TF from lesioned testes was more effective in increasing androgen production than TF from control rats. Unilateral lesions caused an increase in the ability of TF from the disrupted testes to increase the androgen production by normal Leydig cells, as compared to TF from contralateral testes. Thus, locally produced "factor(s)" do appear to modify Leydig cell function. Additional studies using TF from control and bilaterally cryptorchid animals suggest that the ""factor'' in TF is heat-labile; has a molecular size between bovine serum albumin and ovalbumin; exerts a portion of its action independently of cAMP formation; and does not appear to be LH, follicle-stimulating hormone, prolactin, or gonadotropin-releasing hormone. PMID- 2885039 TI - Maintenance of meiotic arrest in isolated rat oocytes by the invasive adenylate cyclase of Bordetella pertussis. AB - Rat oocytes resume meiosis spontaneously in vitro within 3 h after their isolation from the ovarian follicles. We report here that the spontaneous maturation of isolated rat oocytes is preceded by a drop in intracellular levels of cyclic adenosine 3',5'-monophosphate (cAMP). Further experiments were carried out to examine the possible correlation between the meiotic status and cAMP levels within the oocyte. To challenge rat cumulus-free oocytes to generate cAMP, bypassing their own adenylate cyclase, a preparation of an invasive adenylate cyclase from Bordetella pertussis was used. We found a dose-dependent elevation of cAMP levels within these oocytes that corresponded to inhibition of their spontaneous maturation. Persistent inhibition of meiosis was obtained with the continuous presence of the enzymatic preparation, whereas its removal resulted in a transient inhibition associated with a drop in cAMP. We suggest that the presence of elevated cAMP levels in the oocyte is directly responsible for the maintenance of meiotic arrest. PMID- 2885041 TI - Decision making in Huntington's disease and cystic fibrosis. PMID- 2885042 TI - Diagnosis of genetic disease by linkage analysis. PMID- 2885043 TI - DNA diagnosis of autosomal dominant and recessive diseases. PMID- 2885044 TI - [Ca2+ ion enhancement of the inhibitory influence of neuroleptics on the Na, K ATPase of brain synaptosomes]. AB - In the experiments on synaptosomes from the caudate nucleus of the rat brain, neuroleptic drugs (6 types) were found to inhibit the Na, K-ATPase activity considerably stronger (13-51 times, as compared to IC16 values) in the presence of Ca2+ ions (0.25 mM) than in their absence. The enhancement of the inhibitory activity was due to a decrease in the negative cooperation of neuroleptic interaction with the enzyme seen in the absence of Ca2+. PMID- 2885045 TI - [Analysis of the influence of anxiolytics on the pain reactions of rats compared to the effect of morphine]. AB - Anxiolytic agents, buspirone and diazepam, increase the paw lick latency of rats in hot plate test, the effect being dose-dependent and exceeding that of morphine. The action of buspirone was not accompanied by ataxic and sedative effects which were observed in rats on diazepam. Buspirone (up to 25 mg/kg) and diazepam (up to 5 mg/kg) neither change the tail flick latency nor potentiate the action of morphine in this test. The effect of buspirone on the paw lick reaction in rats may be related to the inhibition of emotional-motivation component of pain reaction. PMID- 2885046 TI - [The single nerve ending of the frog sartorius muscle: its ultrastructural characteristics and mediator secretion]. AB - Electron microscopy and extracellular recordings were used for the investigation of structural and functional peculiarities of single frog sartorius muscle nerve terminal. It has been found that the diameter, length of the synaptic contact and quantity of synaptic vesicles decreased from proximal to distal parts of the nerve terminal. A number of varicosities, separated from each other by schwann cells, have been revealed along the course of the nerve terminal. This indicates the existence of an interrupted synaptic contact. Both the evoked and spontaneous transmitter release decreased from the initial to the end parts of the nerve terminal. The data obtained suggest that there is a correlation between structural heterogeneity and the differences in the transmitter release. PMID- 2885047 TI - [Pharmacoethological analysis of the effects of thyroliberin and melanostatin in a model of anxious-defensive behavior in mice]. AB - Psychotropic properties of thyroliberin and melanostatin were studied on the model of timid-defensive behaviour of mice. Oligopeptides increased defensive behaviour and timidity, and decreased intraspecies sociability. GABA deficiency and dopaminergic system blockade increased timid-defensive behaviour of mice. Mobilizing activity of peptides on the agonistic behaviour (aggression and defense) may be explained by their anxiogenic properties. PMID- 2885048 TI - Identification of molecular variants of p210bcr-abl in chronic myelogenous leukemia. AB - The aberrant abl protein product of a chronic myelogenous leukemia (CML) blast crisis cell line (K562) and of five Philadelphia chromosome-positive CML patients in blast crisis were analyzed by an immune complex kinase assay using two antipeptide sera generated against the hydrophilic domain of v-abl and a region within the third exon of the breakpoint cluster region (bcr) respectively. Both the anti-abl and anti-bcr sera detected a 210 kd band in extracts derived from K562 cells and from two CML patients with myeloid blast crisis. p210 was detected by the anti-abl but not the anti-bcr sera in three CML patients with myeloid (one patient) and lymphoid (two patients) blast crisis, indicating the absence of bcr exon 3 in this protein. Southern blot analysis on DNA derived from one of the patients in the latter group was consistent with the break on chromosome 22 occurring 5' to bcr exon 3. Our observations demonstrate that the Philadelphia translocation results in the generation of a chimeric bcr-abl protein with at least two molecular variants, both of which are enzymatically active as protein kinases. PMID- 2885049 TI - Non-Hodgkin's lymphoma containing both B and T cell clones. AB - We describe a patient in whom two lymph node biopsies removed 18 months apart disclosed histologic and immunophenotypic evidence of a non-Hodgkin's lymphoma containing neoplastic lymphocytes of both B and T type. Analyses of immunoglobulin and T cell receptor genes confirmed the presence of separate B and T cell clones. In addition, immunogenotyping revealed the possibility of a second B cell clone within the patient's tumor. Development of a multiclonal lymphoma in this patient may relate to the carcinogenic effects of chemotherapy or to a predisposition for neoplastic transformation of lymphocytes due to a previously diagnosed autoimmune condition. Another possible explanation is that the lymphoma implies the existence in this patient of a transformed lymphocyte-committed stem cell that is capable of generating both B and T lineage clones. PMID- 2885051 TI - Some implications of the high intrasynaptic norepinephrine concentrations in resistance arteries. AB - Norepinephrine concentrations in excess of 10(-4) M are achieved at the post junctional membrane of the adrenergic synaptic cleft in resistance arteries at least for short periods of time. These concentrations are greater than the threshold of low affinity non-alpha-adrenoceptors-'extraceptors', that respond to norepinephrine and would be sufficient to overcome the blockade by alpha adrenoceptor antagonists. The relationship of such activity to the excitatory junction potential and the relevance of this to contraction in vivo remains a matter of conjecture. PMID- 2885050 TI - Identification of a restriction fragment length polymorphism involving the oncogene ETS-1 on chromosome 11q23. AB - Twenty four samples of DNA from 23 unrelated individuals were analyzed for the presence of a novel restriction fragment length polymorphism (RFLP) involving the proto-oncogene ETS-1 at an Xba I site. Four samples from unrelated individuals lacked an Xba I site, giving rise to a longer restriction fragment detectable by Southern analysis; two samples were from normal tissue, and two were from acute myelogenous leukemic blasts. Thus, no association could be found between the RFLP and disease among the individuals studied. Pedigree analysis of another cohort demonstrated Mendelian inheritance consistent with a somatic polymorphism. The practical applications of RFLP analysis in clinical and research settings, and the usefulness of this Xba I RFLP in the study of hematologic malignancies because of its location in 11q23, are discussed. PMID- 2885052 TI - Neurohumoral control of blood vessel tone. Springfield Blood Vessel Symposium. An international symposium held in honor of Che Su, PhD. Springfield, Ill., April 12 13, 1986. Proceedings. PMID- 2885053 TI - Nitrogen and bolus closing volumes: the effect of beta-agonist bronchodilator aerosol. AB - Studies of the effect of beta-agonist bronchodilators on closing volume in normal subjects have produced conflicting results. We studied the possibility that these differences might be due to the different methods of measuring closing volume. We measured closing volume by both the nitrogen washout and the bolus techniques in 19 healthy nonsmoking adults before and after inhalation of salbutamol aerosol. Prior to salbutamol, closing volume measured by the nitrogen method (N2 CV) was significantly smaller (p less than 0.02) than the closing volume measured by the bolus method (bolus CV). After salbutamol inhalation, N2 CV increased significantly (p less than 0.05); however, bolus CV did not change, so that following inhalation of salbutamol there was no significant difference between N2 CV and bolus CV. The increase in N2 CV after salbutamol inhalation was associated with an increase in the slope of phase IV (p less than 0.05). We suggest that beta-agonist bronchodilator aerosol has no effect on closing volume in normal individuals and the apparent increase in N2 CV after bronchodilator is probably an artefact. PMID- 2885054 TI - Analgesia in the neonate. AB - The question of whether a neonate feels pain is a topical one. An extension to this is whether the fetus feels pain. With the likely increase in development of fetal and early neonatal surgery, the indications for and use of analgesics in these patients must be addressed by those who regularly care for them. PMID- 2885055 TI - Complex effects of Gillichthys urotensin II on rat aortic strips. AB - The aim of this study was to determine whether the fish neuropeptide, Gillichthys urotensin II (GUII), possesses significant biological activity on rat aortic strips. On intact strips, pre-contracted by noradrenaline (100 nM), low concentrations (0.1-0.5 nM) of GUII produced relaxations, while higher concentrations (1-10 nM) caused further contraction. On strips rubbed to remove endothelial cells, relaxations were absent but contractile responses to higher concentrations of GUII remained. GUII (0.02-10 nM) produced dose-related contractions of quiescent, intact aortic strips. These contractions consisted of two components, tonic and phasic, and were potentiated in rubbed strips and in the presence of the antioxidant drug hydroquinone (10 microM). Mepacrine (40 microM) and p-bromophenacyl bromide (50 microM) completely abolished contractions to GUII, but indomethacin (10 microM) and nordihydro-guaiaretic acid (10 microM) were without effect. The phasic, but not the tonic, component of the contractile response was inhibited by nitrendipine (200 nM), and was absent in bathing medium from which Ca2+ had been omitted. Addition of EGTA (2 mM) to Ca2+-free bathing medium abolished the residual tonic component. GUII-induced contractions were completely abolished by the calmodulin antagonists trifluoperazine (50 microM) and W-7 (30 microM). It is concluded that GUII, previously considered devoid of significant activity on mammalian tissues, produces potent endothelium-dependent relaxations and endothelium-independent contractions of rat aorta, and possible mechanisms underlying each response are discussed. PMID- 2885056 TI - Non-cholinergic, non-adrenergic nerve-mediated relaxation of pig and human detrusor muscle in vitro. AB - Previously unrecognised, nerve-mediated relaxation in pig and human detrusor muscle is described. The relaxation was mediated via non-cholinergic, non adrenergic and non-prostaglandin transmitter or modulator systems and was present in 12 of 15 detrusor strips from six pigs and in four of 15 detrusor strips from seven patients. A contractile phase preceded relaxation in all strips; in contrast to the contractile phase, relaxation was augmented by an increase in basal tension in a complex way and possibly by the slowest stimulation frequencies. PMID- 2885057 TI - The need for autologous blood transfusion. PMID- 2885058 TI - Acute myelopathy associated with primary infection with human immunodeficiency virus. AB - A 29 year old white homosexual man presented with a two and a half week history of severe sore throat, fever, and extreme fatigue. His symptoms did not respond to antibiotics. He had mild bilateral conjunctivitis, a rash over his chest and back, and enlarged lymph nodes, but examination of the nervous system yielded normal results. He had low total white cell and platelet counts. The results of enzyme linked immunosorbent assay for human immunodeficiency virus (HIV) were equivocal when HIV IgM was detected in serum. Despite treatment with ampicillin his temperature remained high and he developed abnormal neurological signs, including a paraparesis and hyperreflexia of the arms. HIV was isolated from lymphocytes from blood and cerebrospinal fluid. Over the next six weeks the patient improved and was discharged. Two months later abnormal neurological signs persisted in his legs. Although various neurological syndromes associated with seroconversion to HIV have been described, this is probably the first report of a patient with myelopathy at the time of seroconversion. PMID- 2885059 TI - Psychotropic drugs. PMID- 2885060 TI - Who may give blood? PMID- 2885061 TI - Glucose tolerance during long term treatment with a somatostatin analogue. PMID- 2885062 TI - Management of myocardial infarction in Scotland: have clinical trials changed practice? PMID- 2885063 TI - Isolation of clostridia, salmonellae and coccidia from wild pigeons in Japan. PMID- 2885064 TI - Isoniazid-induced alteration of CSF neurotransmitter amino acids in Huntington's disease. AB - During a randomized, double-blind, crossover, placebo-controlled clinical trial of isoniazid (plus pyridoxine) in Huntington's disease (HD), amino acids and related amino compounds were measured in both cerebrospinal fluid (CSF) and plasma utilizing a newly developed high-performance liquid chromatography ion exchange/fluorometric assay method. Results showed that isoniazid (plus pyridoxine) significantly elevated the mean (+/- S.E.M.) levels of gamma aminobutyric acid, aspartate, asparagine, homocarnosine, ornithine, histidine, alpha-aminobutyric acid, isoleucine, leucine and alanine in CSF and the levels of beta-alanine in both CSF and plasma. These alterations can be traced to inhibition of decarboxylation and transamination reactions requiring the cofactor pyridoxal phosphate and may be related to the observed equivocal clinical response in the HD patients. The differential influence of isoniazid on plasma and CSF amino acid profiles suggests that alterations of CNS amino acid metabolism may be reflected in CSF, and that isoniazid-induced alterations of amino acid metabolism in the CNS differ from those in the periphery. PMID- 2885065 TI - Identification and characterisation of cell types accumulating GABA in rat retinal cultures using cell type specific monoclonal antibodies. AB - Monolayer and reaggregate cultures have been established from neonatal rat retina. After 7 days in culture, 60 nM [3H]gamma-aminobutyric acid (GABA) was used to identify cells with a high affinity uptake mechanism for GABA. Approximately 80% of the process-bearing cells were found to be labelled. These cells were identified as amacrine cells by double-labelling experiments combining [3H]GABA uptake with immunocytochemical labelling with monoclonal antibody HPC-1 which in retina is specific for amacrine cells. The ability of cultures to synthesize GABA from glutamate was investigated at various times. Little synthesis was observed during the first few days in culture. This lag was followed by an increase in the amount of synthesis until 3 weeks of culture. When clumps and reaggregate cultures of retinal cells were examined by [3H]GABA uptake, a time-dependent redistribution of labelled cells was observed. After 20 h in culture, GABA-positive cells were distributed over the whole cell mass. Over the next few days, the labelled cells became more common on the outer edge of the aggregates and less common in inner regions. By 7 days of culture, no labelled cell bodies were found on the inside of the aggregates, although such cells could be labelled by [3H]D-aspartate. The results provide positive identification of a subclass of retinal cells in culture, and show that at least one aspect of retinal histogenesis is not dependent upon extra-retinal tissues or the position imposed by the temporal order of retinal cell birth. PMID- 2885066 TI - Time-dependent neurobiological effects of colchicine administered directly into the hippocampus of rats. AB - Rats were given bilateral injections of colchicine into the dorsal and ventral hippocampus. Behavioral, neurochemical and histopathological measurements were taken, up to 12 weeks after surgery. Colchicine produced a consistent increase in spontaneous motor activity, enhanced acoustic startle reactivity, and accelerated acquisition of two-way shuttle box avoidance, but did not affect reactivity to a noxious thermal stimulus. Measurement of dynorphin in the hippocampus indicated that colchicine rapidly depleted this neuropeptide, which is thought to be contained preferentially in the mossy fibers of granule cells of the hippocampus. Colchicine also decreased Met-enkephalin in the hippocampus, but the magnitude of the change (22%) was less than that (89% depletion) observed for hippocampal dynorphin. Examination of hippocampal morphology using light microscopic techniques indicated that colchicine caused approximately 60% degeneration of granule cells in the hippocampus. Although the length of the pyramidal cells was decreased (12-16%), the width of the CA1 and CA3 region of the hippocampus was not affected. These data underscore the importance of the granule cells in the mediation of behavioral processes such as motor activity, startle reactivity and performance of shuttle box avoidance. PMID- 2885067 TI - Failure of subchronic lisuride to modify A10 dopamine autoreceptors' sensitivity. AB - The concept that prolonged treatment with dopamine (DA) mimetics results in a subsensitivity of DA autoreceptors generally is accepted. However, the present study indicates that the administration of a rather specific DA-D2 agonist, lisuride hydrogen maleate (LIS), for one week (200 micrograms/kg/daily) failed to modify the sensitivity of DA autoreceptors of A10 neurons. Indeed, by using extracellular single unit recording in chloral hydrate-anesthetized rats, we observed that neither intravenous apomorphine nor microiontophoresis of DA changed their firing rate-depressant potency when it was estimated at 1 or 3 days after the last LIS injection. A possible interpretation of the results is that the subchronic stimulation of DA-D2 receptors activates an unknown compensatory mechanism which avoids the changes in their sensitivity. Alternatively, the possibility that LIS may also possess antagonistic properties for DA receptors, which might balance the D2 receptors activation, is discussed. PMID- 2885068 TI - Reticulospinal neurones activate excitatory amino acid receptors. AB - Paired intracellular recordings were used to study the monosynaptic excitatory postsynaptic potentials (EPSP) in lamprey motoneurones evoked by stimulation of single reticulospinal Muller and Mauthner cells. The chemical component of the synaptic potentials was depressed by both application of the non-selective excitatory amino acid antagonists kynurenic acid and cis-2,3-piperidine dicarboxylate. The N-methyl-D-aspartate (NMDA) antagonists Mg2+ and 2-amino-5 phosphonovalerate caused a selective depression of a late component of the EPSP. Thus, fast-conducting reticulospinal neurones appear to release an excitatory amino acid acting at both NMDA and non-NMDA receptors. PMID- 2885069 TI - Colchicine lesions in the rat hippocampus mimic the alterations of several markers in Alzheimer's disease. AB - An infusion of colchicine into the hippocampi of rats resulted in destruction of hippocampal cells. Twelve days after infusion, preoperative trained colchicine treated rats showed a significant decrease in choice accuracy in a T-maze learning task. There was also local reduction in choline acetyltransferase (ChAT) activity and significant losses of 55-kDa protein in the soluble fraction and of 50-kDa protein in myelin and synaptosomal fractions in the hippocampi of colchicine-lesioned rats. There was a marked increase in [3H]glutamate binding in the hippocampus and cortex. In contrast, [3H]quinuclidinyl benzilate binding in the hippocampus was slightly reduced, whereas [3H]dihydroalprenolol binding was not affected by the colchicine treatment. Scatchard analysis revealed that the increase in glutamate binding is due to an increase in the number of glutamate receptors without significant change in their affinity. Some of the changes caused by hippocampal infusion of colchicine resemble those seen in Alzheimer's disease suggesting the use of such rats as one model for the disease. PMID- 2885070 TI - Immunocytochemical localization of glutamic acid decarboxylase (GAD) and glutamine synthetase (GS) in the area postrema of the cat. Light and electron microscopy. AB - The present study was designed to investigate the existence of two key enzymes involved in the metabolism of gamma-aminobutyric acid, glutamic acid decarboxylase (GAD) and glutamine synthetase (GS), in the area postrema (AP) of the cat. The results showed that punctuate structures of variable size corresponding to axon terminals, exhibited GAD-immunoreactivity and were distributed in varying densities. The greatest accumulation was present in the caudal and middle segment of the AP and particularly in the area subpostrema, where the aggregation of terminals was extremely dense. The population of the GAD labelled axon profiles gradually decreased toward the solitary complex. No neuronal bodies were labelled in our preparations. The electron microscopic studies revealed a large variety of contacts between labelled terminals and unlabelled dendrites, axons or neurons. The possibility that the GAD immunoreactive terminals might correspond to vagal afferent projections was discussed on the basis of our observations and of other studies that employed horseradish peroxidase or degeneration methods. GS-immunoreactivity was seen in ependymoglial cells of the AP, particularly toward the caudal region, and in astrocytes and their processes of the AP proper. The latter were frequently observed around capillaries. The presence of both GAD-immunoreactive profiles and GS-immunostained ependymoglial cells and astrocytes in the AP, provided further immunocytochemical evidence of the functional correlation between the two enzymes. PMID- 2885071 TI - Induction of gamma-glutamyl transpeptidase in cultured cerebral endothelial cells by a product released by astrocytes. AB - gamma-Glutamyl transpeptidase (gamma GTP) is an enzyme found in cerebral capillary endothelial cells, the presumed site of the blood-brain barrier, but not in endothelial cells lining blood vessels in other parts of the body. Using a line of mouse cerebral microvessel endothelial cells (ME-ly cells) and a sensitive colorimetric assay to measure gamma GTP levels we demonstrated that primary cultures of mouse astrocytes and a line of rat C6 glioma cells released a soluble product(s) that induced the production of gamma GTP in cultured endothelial cells by 34% and 39%, respectively, over control levels. Cerebrovascular smooth muscle cells had no significant effect on gamma GTP levels in ME-ly cells, and the astrocyte product(s) had no effect on rabbit aortic endothelial cells. The induction of gamma GTP levels in ME-ly cells was apparent after one day of exposure to the astrocyte product(s) and increased in magnitude with increasing time of exposure of the ME-ly cells to the product(s). Removal of the product(s) from the ME-ly cells resulted in a return to control levels of gamma GTP in the ME-ly cells within 2 days. The presence of a protein synthesis inhibitor during incubation with the product(s) blocked the induction of gamma GTP in ME-ly cells, and treatment of the product(s) with 200 U/ml TPCK-trypsin destroyed its inductive properties.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885072 TI - Mediation of separation distress by alpha 2-adrenergic mechanisms in a non-human primate. AB - This study provides the first behavioral evidence in support of an alpha adrenergic mechanism underlying imipramine's amelioration of separation distress. The rate of separation-induced vocalization by adult squirrel monkeys was decreased by imipramine and the alpha 2-adrenergic agonist clonidine, and increased by the alpha 2-adrenergic antagonist yohimbine. Yohimbine, but not the alpha 1-antagonist prazosin, reversed the clonidine effect suggesting that drugs acting directly on alpha 2-receptors may have a role in management of separation anxiety. PMID- 2885074 TI - Differential effect of functional olfactory deprivation on the GABAergic and catecholaminergic traits in the rat main olfactory bulb. AB - The effects of the unilateral olfactory naris closure were studied immunohistochemically in the main olfactory bulb of adult rats. In the olfactory deprived bulbs, the tyrosine hydroxylase-immunoreactive elements in the glomeruli and the juxtaglomerular region decreased drastically, whereas the glutamate decarboxylase-immunoreactive elements in these regions showed no appreciable changes, indicating the differential effects of olfactory deprivation on catecholaminergic and GABAergic traits in spite of their coexistence in some neurons in these regions. PMID- 2885073 TI - Neostriatal cholinergic neurons receive direct synaptic inputs from dopaminergic axons. AB - We used an electron microscopic 'mirror technique' to determine whether cholinergic neurons are in direct synaptic contact with dopaminergic axons in the rat neostriatum. Tyrosine hydroxylase-immunoreactive axons make synaptic contacts with the somata and proximal dendrites of large choline acetyltransferase immunoreactive striatal neurons which are thought to be interneurons. This provides morphological evidence that nigrostriatal dopaminergic neurons can influence monosynaptically the striatal cholinergic neurons. PMID- 2885075 TI - Effect of starvation on hypothalamic tyrosine hydroxylase activity in adult male rats. AB - The activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in norepinephrine synthesis, was determined in the mediobasal hypothalamus of adult male rats during acute and semistarvation. 3,4-Dihydroxyphenylalanine (DOPA) formed by TH was measured using high-performance liquid chromatography (HPLC). Acute starvation, as well as 3 weeks of semistarvation on a high-protein low carbohydrate diet (CST PR) reduced TH activity significantly. Three weeks of a low-protein high-carbohydrate diet (CST KH) did not affect TH activity. While maximal velocity (Vmax) is significantly diminished in acute starvation and in semistarvation with a high-protein low-carbohydrate diet, Kd-values for tyrosine were not changed. These results suggest that TH activity in the brain contributes to decreased norepinephrine (NE) turnover in starvation. PMID- 2885077 TI - Chick eye extract promotes expression of a cholinergic enzyme in sympathetic ganglia in culture. AB - Previous studies have demonstrated that, in rat, individual sympathetic neurons can express both adrenergic and cholinergic biosynthetic enzymes in culture. Moreover, the levels of these enzymes can be regulated by factors present in their environment. In the present study, we sought to determine whether cultures of chick sympathetic neurons express both adrenergic and cholinergic enzymes, whether both enzymes are expressed in the same neurons, and whether the levels of these enzymes can be influenced by environmental factors. In our system, we tested one such factor found in embryonic eye extract (EEE) which has been shown to specifically increase the activity of the cholinergic enzyme choline acetyltransferase (ChAT) in cultures of chick parasympathetic neurons Varon et al., Brain Res., 173 (1979) 29-45; Nishi and Berg. J. Neurosci., 1 (1981) 505 513). At various times in vitro, cultures were analyzed using biochemical, immunocytochemical and autoradiographic techniques. We found that only those cultures of sympathetic neurons supplemented with EEE developed detectable levels of ChAT enzyme activity at 2 days, which increased significantly by 14 days in vitro. Supplementation with EEE did not affect the level of tyrosine hydroxylase (TH) activity. Furthermore, irrespective of nutrient medium, all neurons in all cultures contained TH immunoreactivity and possessed a high-affinity amine uptake system as demonstrated by autoradiography. These studies suggest that neurons of chick sympathetic ganglia can be influenced by factors present in EEE to express a cholinergic enzyme and that this enzyme is coexpressed by cells also exhibiting an adrenergic phenotype. PMID- 2885076 TI - Neuron-like cells in long-term neural crest cultures are not targets of nerve growth factor. AB - It has been shown previously that a subpopulation of long-term (7-14 days) cultured neural crest cells undergoing differentiation possesses receptors for nerve growth factor (NGF). These cells are likely to be targets of NGF during the early stages of embryonic development. This study was conducted to determine whether cells exhibiting neuron-like characteristics (i.e. process formation, presence of putative neurotransmitters) in neural crest cultures have NGF receptors. This was accomplished by combining 125I-NGF radioautography and immunocytochemistry using antibodies against tyrosine hydroxylase, serotonin, and vasoactive intestinal polypeptide. Examination of light microscopic radioautographs revealed that none of the neuron-like cells with tyrosine hydroxylase-like, serotonin-like, or vasoactive intestinal polypeptide-like immunoreactivity bound 125I-NGF, and, therefore, do not possess NGF receptors. It is not known whether the lack of NGF receptors on neuron-like cells is due to the early developmental stage of these cells, or is caused by a difference in the microenvironment in vitro as compared to in vivo. The identity of the cultured neural crest cells which do possess NGF receptors remains to be determined. PMID- 2885078 TI - An unusual pheochromocytoma associated with an androgen secreting adrenocortical adenoma. Evaluation of its polypeptide hormone, catecholamine, and enzyme characteristics. AB - Our patient had a left suprarenal mass. His blood pressure was normal, but his urinary catecholamines (CA), vanillylmandelic acid (VMA), total metanephrines (TMn) and 5-hydroxyindolacetic acid (5HIAA) were elevated. In addition, he had elevated, nonsuppressible urinary 17-ketosteroids (17KS) and androsterone, but his urinary 17-hydroxycorticoids (17OHCS) and free cortisol were normal, as were his plasma cortisol and ACTH. After resection of the suprarenal mass, the patient's urinary hormone values reverted to normal. The mass contained a pheochromocytoma and an adrenocortical adenoma. The pheochromocytoma was unusual in that it contained very little norepinephrine (NE) and dopamine (DA) and an abundance of epinephrine (E) despite normal enzyme concentrations. Electron micrographs showed primarily E granules with few of the NE-type. The immunoperoxidase histochemical stains for vasoactive intestinal peptide (VIP) and serotonin (S) were strongly positive. The patient's blood pressure may have been normal because his pheochromocytoma secreted E, VIP, or S. The associated adrenocortical adenoma produced no symptoms and was probably coincidental. PMID- 2885079 TI - Somatostatinoma of Vater's papilla and of the minor papilla. AB - Two cases of somatostatinomas of the major and minor papilla are reported. The tumors were characterized by solid trabecular and tubular arrangements of tumor cells and in one case by the presence of microvilli and psammoma bodies. The tumor cells contain many amine precursor uptake and dicarboxylation (APUD) granules with a diameter of 300 to 500 nm and low electron density. Immunoperoxidase stain showed intense staining only for somatostatin and low density of neuron-specific enolase. Those tumors either resulted from pluripotent endocrine cells or from D-cells of the mucosa or glands of the papilla. PMID- 2885080 TI - Adjuvant chemotherapy for advanced head and neck squamous carcinoma. Final report of the Head and Neck Contracts Program. AB - To determine the efficacy of adjuvant chemotherapy in patients with advanced head and neck squamous carcinoma, the National Cancer Institute initiated a multi institutional, prospective randomized trial termed the Head and Neck Contracts Program. Between 1978 and 1982, 462 patients with resectable Stage III or IV cancers of the oral cavity, larynx, or hypopharynx were randomly assigned to receive one of three treatment options: induction chemotherapy consisting of a single course of cisplatin and bleomycin followed by standard therapy (surgery and postoperative radiotherapy); induction chemotherapy and standard therapy followed by maintenance chemotherapy which consisted of six cycles of monthly cisplatin; or standard therapy alone. Toxicity from the chemotherapy regimens was minimal. Induction therapy resulted in an overall complete response of 3% and a partial response in 34% of patients. With a median follow-up of 61 months, overall survival and disease-free survival were not markedly different among the three groups (P = 0.86 and P = 0.16, respectively). The incidence of distant relapse was reduced in the maintenance group compared to standard or induction groups (P = 0.025 and P = 0.021, respectively) and time to first distant relapse was prolonged (P = 0.032 and P = 0.022, respectively). The results confirm the feasibility of administering chemotherapy prior to surgery or radiation in patients with head and neck cancer but fail to demonstrate a significant impact of one cycle of induction chemotherapy on clinical outcome. The suggestion that distant relapse rates may be reduced with the addition of maintenance chemotherapy supports the need to test traditional adjuvant approaches in patients with advanced head and neck cancer. PMID- 2885081 TI - Linkage analysis of multiple endocrine neoplasia type 2A (MEN-2A) and three DNA markers on chromosome 20: evidence against synteny. AB - Members of four families in which multiple endocrine neoplasia type 2A (MEN-2A) is segregating were genotyped for three chromosome #20 DNA markers. Close linkage is excluded for the genetic locus of MEN-2A (MEN2A) with each marker locus tested. Using multipoint analysis, the MEN2A locus was excluded from a region 32.5 cM in length encompassing D20S5 and D20S6, two loci that previously had been mapped to the chromosome 20p12.2 region containing the putative deletion associated with MEN-2. In total, we excluded approximately 90.5 cM of chromosome #20 as a possible location of the MEN2A locus. The data from this study do not support increased recombination on the short arms of chromosome #20 and were insufficient to support heterogeneity of MEN-2A as possible explanations for failure to detect linkage between MEN2A and D20S5 or D20S6. PMID- 2885082 TI - Loss of heterozygosity for a chromosome 3 sequence presumably at 3p21 in small cell lung cancer. AB - A recombinant DNA fragment detecting a chromosome #3 restriction fragment length polymorphism presumably at p21 was hybridized to HindIII-digested DNA isolated from the leukocytes of 12 patients of small cell lung cancer. Four of them appeared to be heterozygous. Analysis of tumor material from these four patients revealed homozygosity for either one or the other restriction fragment in every case. Our findings suggest the presence on the short arm of chromosome #3 of a recessive mutant cancer gene contributing to the development of small cell lung cancer. PMID- 2885083 TI - A new glucocorticoid receptor detected in host rat liver but not in various hepatomas. AB - Previously a new glucocorticoid receptor (Peak C), which eluted with 0.12 to 0.14 M NaCl from DEAE-cellulose column, was identified in addition to another receptor (Peak B), a classic type of glucocorticoid receptor, which eluted with 0.05 to 0.08 M NaCl. Peak C appeared after stress or injection of a high dose (20 micrograms/100 g body weight) of dexamethasone into rats. Peak C was also detected in the liver of rats bearing various tumors, but it was not found in malignant tumors (Yoshida sarcoma and Yoshida ascites hepatoma AH 130), a less malignant Yoshida ascites hepatoma (LY-5), or in minimal deviation-type hepatomas (Morris hepatomas 7316A and 7794A). The absence of Peak C in these tumors coincided with the inability of the glucocorticoid to induce tryptophan oxygenase in these tumors and in the liver of rats during early postnatal development. Peak B was consistently observed in various hepatomas and immature rat liver with capability to induce tyrosine aminotransferase. Thus Peak C appeared to be a highly differentiated type of glucocorticoid receptor mediating specific hormone actions and to be present in mature liver cells, but not in immature liver or tumor cells, even of the minimal deviation type. PMID- 2885084 TI - Organ colonization pattern of retinoic acid-treated and -untreated mouse embryonal carcinoma F9 cells. AB - The mouse embryonal carcinoma cell line F9 differentiates into parietal endoderm cells after a 3-day exposure to retinoic acid and dibutyryl cyclic AMP. Using the experimental metastases assay, we investigated the organ colonization properties of RA-treated and -untreated populations of F9 cells. The results show that untreated F9 cells colonize the liver with a high degree of specificity while the treated populations colonize the lungs. Cells derived from a lung colony colonized only the liver unless they were treated with RA. However, removal of the inducer from culture of differentiated cells did not cause reversal of the lung colonization potential. Our observations also indicate that it is unlikely that lung colonization is due to cell aggregation or to interaction between differentiated and undifferentiated cells. Taken together, these results suggest that RA induces the observed changes of organ colonization properties of F9 cells. PMID- 2885085 TI - Multidrug resistance. AB - Multidrug resistance describes a complex phenotype whose predominant feature is resistance to a wide range of structurally unrelated cytotoxic compounds, many of which are anticancer agents. This phenotype occurs frequently in mammalian cell lines and transplantable tumours selected for resistance to a single drug. Reduced cellular accumulation of the drugs involved appears to account for the resistance. This may be a consequence of reduced drug influx, increased drug efflux, or both. A wide variety of biochemical changes have been identified in multidrug resistant cell lines, the most consistent of which is the increased expression of P-glycoprotein, a conserved, high molecular weight, plasma membrane glycoprotein. The level of P-glycoprotein expression correlates with the degree of drug resistance in a variety of different cell types. In a number of multidrug resistant cell lines, overexpression of P-glycoprotein results from gene amplification. While the function of P-glycoprotein is unknown, independent lines of evidence support the notion that P-glycoprotein is the causative molecule mediating the multidrug resistance phenotype. Significant levels of P glycoprotein expression have been detected in some biopsy specimens from patients with ovarian and sarcoma tumours. These findings suggest that multidrug resistant tumour cells can occur in human malignancies. The presence of such cells may affect the outcome of chemotherapy. PMID- 2885086 TI - Recent advances in the management of tics. PMID- 2885087 TI - Parkinson's disease and dementia. PMID- 2885088 TI - The pharmacological management of essential tremor. PMID- 2885089 TI - Tardive dyskinesia: prevention and treatment. PMID- 2885090 TI - Synthesis of p-nitrophenyl 5-acetamido-3,5-dideoxy-alpha-D-glycero-D-galacto-2 nonulopyranosid onic acid, a chromogenic substrate for sialidases. PMID- 2885091 TI - Control of immune responsiveness by regulatory T lymphocytes. PMID- 2885092 TI - Relevance of autocytotoxic and autoregulatory lymphocytes in the maintenance of self tolerance. AB - The state of self tolerance may well be an amalgam of many processes including (but not necessarily limited to) clonal deletion and specific suppressor cell networks. Cells with autoaggressive potential are clearly present in the blood of healthy individuals and have been implicated in diseases states. Given the critical importance of maintaining self tolerance, it is not at all surprising that several mechanisms appear to play a role in this process. Attempts to harness and manipulate these various mechanisms in order to prevent allograft rejection or to treat autoimmune diseases should prove to be exciting areas of investigation in the years ahead. PMID- 2885093 TI - [The effect of betalytics on blood circulation in the extremities of patients with lower extremity ischemic disease]. PMID- 2885094 TI - [Initial experience with the diagnosis of hemophilia A using molecular genetics]. PMID- 2885095 TI - A fused mitochondrial gene associated with cytoplasmic male sterility is developmentally regulated. AB - Sequencing of an open reading frame associated with cytoplasmic male sterility (CMS) in Petunia has revealed a gene fusion (the Pcf gene) containing the 5' flanking and amino-terminal transmembrane segment of the ATP synthase proteolipid gene (atp9), parts of the cytochrome oxidase subunit II (coxII) coding region, and the carboxyl terminus and 3'-flanking region of an unidentified reading frame (urfS). The coxII region has several small deletions and tandem repeats that remove all of the segments coding for the residues involved in copper binding, but may possibly maintain the cytochrome c binding site. Normal atp9 and coxII genes and their transcripts are also present in the sterile cytoplasm. S1 nuclease protection studies identify fused gene transcripts only in CMS lines, with an increase in transcript amount in anthers relative to leaves. PMID- 2885096 TI - Primary cilia cycle in PtK1 cells: effects of colcemid and taxol on cilia formation and resorption. AB - The effects of colcemid (0.16-1.0 microM) and taxol (10 microM) on the primary cilia cycle in PtK1 cells were studied by antitubulin immunofluorescence microscopy and by high-voltage electron microscopy of serial 0.25-micron sections. Although these drugs induce a fully characteristic rearrangement (taxol) or disassembly (colcemid) of cytoplasmic microtubules, neither affects the structure of primary cilia formed prior to the treatment or the resorption of primary cilia during the initial stages of mitosis. Cells arrested in mitosis by taxol or colcemid remain in mitosis for 5-7 h at 37 degrees C and then form 4N "micronucleated" restitution nuclei. Formation of primary cilia in these micronucleated cells is blocked by colcemid in a concentration-dependent fashion: normal cilia with expanded (ie, bulbed) distal ends form at the lower (0.16-0.25 microM) concentrations, while both cilia formation and centriole replication are inhibited at the higher (greater than or equal to 1.0 microM) concentrations. However, even in the presence of 1.0 microM colcemid, existing centrioles acquire the appendages characteristically associated with ciliating centrioles and attach to the dorsal cell surface. Continuous treatment with colcemid thus produces a population of cells enriched for the early stages of primary cilia formation. Micronucleated cells formed from a continuous taxol treatment contain two normal centriole pairs, and one or both parenting centrioles possess a primary cilium. Taxol, which has been reported to stabilize microtubules in vitro, does not inhibit the cell-cycle-dependent assembly and disassembly of axonemal microtubules in vivo. PMID- 2885097 TI - Marine natural products. XVII. Nephtheoxydiol, a new cytotoxic hydroperoxy germacrane sesquiterpene, and related sesquiterpenoids from an Okinawan soft coral of Nephthea sp. (Nephtheidae). PMID- 2885098 TI - Study of the interactions between sulfamethizole and alclofenac, diclofenac or tiaprofenic acid in rats. PMID- 2885100 TI - Metabolic cooperation in SK-HEP-1 human hepatoma cells following treatment with benzodiazepine tranquilizers. AB - The ability of three benzodiazepine tranquilizers, diazepam, oxazepam and chlordiazepoxide chlorhydrate to block metabolic cooperation between human hepatoma cells was analysed using autoradiographical monitoring. Independent tests were performed with compound concentrations varying from 1 to 50 micrograms/ml. The results showed that at a toxic dose of 50 micrograms/ml diazepam and oxazepam markedly inhibited metabolic cooperation and that oxazepam remained effective at a lower, non-toxic, dose (10 micrograms/ml). Chlordiazepoxide chlorhydrate was found to be less toxic than diazepam and oxazepam and did not interfere with metabolic cooperation at any concentration up to 50 micrograms/ml. PMID- 2885101 TI - Gamma-glutamyl transpeptidase activity during carcinogenesis of hamster buccal pouch epithelium. AB - Gamma-glutamyl transpeptidase (GGT) activity has been demonstrated histochemically in a number of experimentally induced neoplasms and has been suggested as a label for potential precursors for the development of squamous cell carcinomas. This study explores the kinetics of GGT-stained cell populations, their correlation with the hypothesized initiated cells and evidence of malignant transformation of epithelium in hamster buccal pouch by a 15-week regime of tri-weekly topical application of 7, 12-dimethylbenz[a]anthracene (DMBA) in mineral oil. GGT-positive foci were detected histochemically in tissue sections as early as 1 week after application of the carcinogen, when there was no morphological evidence of dysplasia. The average number of the GGT-positive foci in each experimental period was found to increase with time. Even though the majority of the foci were small, consisting of only a single cell or a small group of cells, a few larger GGT-positive lesions were noted, particularly in the later period of the experiment. A total of 66 grossly visible neoplasms were found. Thirty-seven of these were submitted for GGT staining. Thirty-two (86.5%) of these showed patchy GGT activity, primarily in the superficial epithelial cells and/or the keratin. In the non-neoplastic epithelium, the GGT staining could involve any or all layers of cells. GGT activity was not detected in untreated or mineral oil-treated mucosa. The results of this study support the hypothesis that GGT activity may label potential precursors for the development of squamous cell carcinomas. PMID- 2885103 TI - Parasympathetic effects on in vivo rat heart can be regulated through an alpha 1 adrenergic receptor. AB - A prejunctional mechanism involving an alpha 1-adrenergic receptor may exert control on the release of acetylcholine from parasympathetic nerve endings in the heart. To test this hypothesis in vivo, rats were prepared for electrical stimulation of the vagus nerves. Blood pressures and heart rates were monitored, and the animals were treated with alpha-agonists and alpha-antagonists. The alpha 1-selective agonist phenylephrine significantly attenuated vagally induced bradycardia in a dose-dependent fashion (ED50 = 19 micrograms/kg). This is consistent with the hypothesis that there is alpha-adrenergic inhibition of ACh release. In contrast, the alpha 2-selective agonist, BHT-920, caused no change in heart rate during vagal stimulation. The effects of phenylephrine to raise heart rate and blood pressure during vagal stimulation were blocked by the alpha 1 selective antagonist prazosin (ID50 approximately 1 microgram/kg) but not by the alpha 2-selective antagonists yohimbine and rauwolscine. This further supports an alpha 1 assignment to the prejunctional adrenergic receptor mechanism, which can regulate the release of acetylcholine from cardiac parasympathetic neurons. PMID- 2885102 TI - Carcinogen treatment increases glutathione hydrolysis by gamma-glutamyl transpeptidase. AB - The effect of carcinogen treatment on gamma-glutamyl transpeptidase (GGT) mediated hydrolysis of GSH to glutamate and cysteinylglycine in the blood and bile compartments was investigated in livers perfused in situ. Treatment of rats with 40 p.p.m. diethylnitrosamine (DEN) in the drinking water or 0.02% 2 acetylaminofluorene (AAF) in the diet for 50-60 days increased GGT activity in liver homogenates by 100 and 800% respectively. Bile flow and the sum of glutamate and glutathione (GSH) efflux into the bile of perfused livers was not affected by carcinogen treatment. However, the ratio of GSH to glutamate in bile was 2.1, 1.1 and 0.2 in livers from control, DEN- and AAF-treated rats respectively. Pretreatment with L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5 isoxazoleacetic acid (AT125) decreased GGT activity in liver homogenates by about 85% and elevated the ratio of GSH to glutamate in the bile to 3.2 in all groups. Thus, the hydrolysis of GSH to glutamate in the bile of perfused livers correlated with the degree of induction of GGT by DEN and AAF treatments. Exogenous GSH (10 microM) infused into the portal vein of perfused livers from control, DEN- and AAF-treated rats was recovered completely in the effluent perfusate. Pretreatment with AT125 had no effect on the recovery of exogenous GSH in the effluent perfusate. Thus, metabolism of GSH in the blood space was not detected after short-term carcinogen treatment. To increase the possible hydrolysis of GSH in the perfusate, rats were treated for 130-180 days with DEN and GSH (60 microM) was infused into the hepatic artery of livers perfused simultaneously via the hepatic artery and portal vein. Only 50% of the infused GSH was recovered in the effluent perfusate of perfused livers from DEN-treated rats. In contrast, significantly more GSH (80-90%) was recovered from livers from control rats or DEN-treated rats that had received AT125 pretreatment. In addition AT125 pretreatment increased the basal rates of GSH efflux in livers from DEN-treated rats. Thus, DEN-induced GGT metabolizes GSH entering the liver via the hepatic artery. Furthermore, GGT may act to decrease the net efflux of GSH from perfused livers by causing the intraorgan recycling of GSH and its constituent amino acids. PMID- 2885104 TI - Effects of anoxia on kinetics of [13N] glutamate and 13NH3 metabolism in rabbit myocardium. AB - Positron emission tomography is a unique noninvasive imaging technique that provides cross-sectional images of radiotracer concentrations in myocardium and permits measurement of blood flow as well as metabolism. Ammonia and glutamate have been labeled with the positron-emitter 13N (half-life 10 minutes) for use with positron emission tomography as tracers of flow and metabolism, respectively. In order to characterize the fate of these 13N-labelled compounds in myocardium, isolated rabbit interventricular septa were used to study the kinetics of [13N] glutamate ([13N]glu) and 13NH3 under aerobic and anoxic conditions. Tissue analyses 6 minutes after injection of a [13N]glu bolus into myocardium revealed that 70% of the 13N-label was present in [13N]glu 12%, 11%, and 4% in [13N]alanine ([13N]ala), [13N]aspartate ([13N]asp), and [13N]glutamine ([13N]gln), respectively. The corresponding relative specific activities were 1.0:0.4:0.5:0.01. Anoxia resulted in a significant increase in [13N]ala with a reduction in [13N]glu. This was consistent with increased pyruvate production due to increased anaerobic glycolysis and transamination of pyruvate with [13N]glu to yield [13N]ala. In support of this, addition of 2 mM pyruvate to the perfusate under control conditions produced a tissue distribution of 13N similar to that with anoxia. Six minutes after a bolus of 13NH3 during both control and anoxic conditions, 60% of the tissue 13N-label was in [13N]gln with no detectable amounts in other amino acids. The rest of the 13N-label was in 13NH3. Time activity curve analyses demonstrated that anoxia significantly reduced the tissue retention of 13N-label from 13NH3 but not from [13N]glu. Thus, 13N from 13NH3 and [13N]glu was retained in tissue by different mechanisms involving glutamate, which were affected differentially by anoxia. These results suggest that positron emission tomography imaging with 13NH3 and [13N]glu in combination may be useful in identifying ischemic myocardium. PMID- 2885099 TI - Enzymes of glutathione metabolism as biochemical markers during hepatocarcinogenesis. AB - Enzymes of glutathione metabolism, particularly gamma-glutamyltransferase (GGT) and glutathione S-transferase (GST), play a role in multistage hepatocarcinogenesis. The enhanced expression of these enzymes in preneoplastic altered hepatic foci, nodules, and hepatocellular carcinomas has been demonstrated after treatment with a variety of initiating and promoting agents. Glutathione is necessary for the detoxification of xenobiotics and carcinogens and for cell replication. Induction of GGT in altered hepatocytes may permit these cells to utilize extracellular glutathione to preserve their internal glutathione levels. GST induction allows glutathione utilization for the protection of the altered hepatocyte in an environment of exposure to xenobiotics, such as promoting agents. Thus, the combined effects of GGT and GST, in a toxic environment, may provide for the enhanced proliferation observed in preneoplastic hepatocytes. New clinical and research opportunities may involve the use of GGT and the placental isozyme of GST (PGST) as markers of preneoplasia and neoplasia in humans. Many factors, such as hormones, diet, and exposure to initiating and promoting agents, influence GGT and GST expression. The recent cloning of cDNAs to GGT and PGST offers opportunities for the study of factors involved in the genetic expression of these two enzymes. Coupled with the use of hepatocyte culture and transplantation, the factors involved at the molecular level in the creation of hepatocellular neoplasia may be discovered. PMID- 2885105 TI - Alpha 1-adrenoceptor activity regulates release of adenosine from the ischemic myocardium in dogs. AB - The goal of this study was to test the hypothesis that alpha 1-adrenoceptor activity plays a key role in the release of adenosine from the ischemic myocardium. In 51 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the carotid artery, and adenosine release into the local coronary vein was measured by the radioimmunoassay technique following the reduction of perfusion pressure for 20 minutes under alpha 1-, alpha 2-, and beta-adrenoceptor attenuations. Adenosine and lactate concentrations in the coronary arterial and venous blood sampled from the perfused area were determined, as well as fractional shortening. In the untreated condition, adenosine release was significantly (p less than 0.01) increased from 1.7 +/- 0.8 (SEM) to 8.8 +/- 1.3 nmol/100 g/min, 20 minutes after the onset of hypoperfusion (coronary blood flow: 28 +/- 2 ml/100 g/min) following the initial overshoot release. Neither beta- nor alpha 2-adrenoceptor attenuation affected the increase in adenosine release during hypoperfusion except for the slight attenuation of the overshoot release by beta-attenuation. In contrast, intracoronary infusions of prazosin and phentolamine during coronary hypoperfusion markedly attenuated (p less than 0.01) release of adenosine (1.8 +/ 0.7 nmol/100 g/min at 20 minutes). The extents of decreases in fractional shortening and lactate production were comparable between the untreated and alpha 1-adrenoceptor attenuation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885107 TI - Secondary prevention of coronary artery disease. PMID- 2885106 TI - Molecular cloning of human angiotensinogen cDNA and evidence for the presence of its mRNA in rat heart. AB - Human angiotensinogen cDNA clone was isolated from a liver cDNA library using a 32-nucleotide-long, synthetic oligonucleotide. The cDNA insert was 1,030 bp long and coded for the secretory and biologically active angiotensin II regions of the angiotensinogen molecule. The RNA from rat liver, brain, and heart was analyzed by the Northern hybridization procedure using nick translated angiotensinogen cDNA as a probe. In addition to liver, the angiotensinogen mRNA is present in the brain and the heart. The angiotensinogen mRNA in the heart is at least fourfold to fivefold more abundant as compared with the liver. We also provide evidence that angiotensinogen mRNA is present in the rat atria and right ventricle but not detectable in the left ventricle. The size of the angiotensinogen mRNA is the same from all three of the tissues, as judged by their electrophoretic mobilities. PMID- 2885109 TI - [Role of the caudate nucleus in acupuncture analgesia (minireview)]. PMID- 2885108 TI - Sudden cardiac death. Neural-chemical interactions. PMID- 2885110 TI - Reflotron assays of alanine aminotransferase and gamma-glutamyltransferase in whole-blood samples evaluated. AB - We evaluated the Reflotron (Boehringer Mannheim) system for measuring activities of alanine aminotransferase (EC 2.6.1.2) and gamma-glutamyltransferase (EC 2.3.2.2). Within- and between-day precision were comparable with conventional analytical methods. The linear range of the methods extended to more than 40-fold the upper limit of the reference range. The methods were not influenced by moderate changes in blood rheology and also tolerated some variation in sample volume applied. We consider these methods to be suitable for use in satellite or physicians' office laboratories (with appropriate training of operators), and they can produce results that agree satisfactorily with those determined in routine laboratory practice. PMID- 2885111 TI - Intra-individual variation of analytes in serum from patients with chronic liver diseases. AB - The average biological intra-individual CV in 20 patients with chronic liver diseases (CLD), estimated for 14 analytes during a stationary phase, significantly exceeded that for a normal group in the cases of Na+, K+, Cl-, total protein, albumin, cholinesterase, hemoglobin, and alpha-amylase; it did not differ significantly from the normal group for cholesterol, alkaline phosphatase, aspartate aminotransferase, and alanine aminopeptidase; and it was significantly lower than in the normal group for alanine aminotransferase and gamma glutamyltransferase. There were no significant sex-related differences in mean intra-individual variation in CLD patients. Individual values were gaussian distributed for all analytes, including enzymes. The estimated biological component of intra-individual variation and the analytical variation as determined for each laboratory can be used to derive decision-making criteria in monitoring CLD. PMID- 2885113 TI - Lithium-specific pathological electroencephalographic changes: a successful replication of earlier investigative results. AB - In three independent comparisons, patients treated with lithium carbonate (either alone or in combination with other agents) were contrasted with both medication free and other psychotropic medicated patients, in terms of the prevalence of abnormal generalized slowing and paroxysmal diffuse delta activity in the clinical EEG. In all samples, abnormal EEG changes occurred in from 30.3 to 39.4% of lithium treated patients as contrasted with from only 1.5 to 4.6% of medication free controls. In all comparisons, the prevalence of abnormal EEGs was significantly higher for lithium treated patients than for patients free of medication or those treated with other psychotropic agents. EEG changes are reversible with discontinuance of lithium, and their role in suggesting potential early neurotoxicity is discussed. PMID- 2885112 TI - A simple chromogenic assay for arylsulfatase A. AB - Arylsulfatase A hydrolyzes the artificial chromogenic substrate 4-nitrocatechol sulfate at 0 degree C at a rate of 24% of that at 37 degrees C whereas arylsulfatase B is almost inactive at 0 degree C. Based on this observation, a simple assay was developed which permits the accurate determination of low residual arylsulfatase A activities in cultured skin fibroblasts of infantile, juvenile and adult MLD patients and pseudodeficient individuals. In cultured skin fibroblasts, the following residual activities were found with this assay system: late-infantile patients, 0.0%, one juvenile patient, 1.0%, adult patients, 4.4 14% of normal average. healthy pseudodeficient probands ranged between 18% and 32%. PMID- 2885114 TI - Somatostatin and the stomach. PMID- 2885115 TI - Diagnosis of arylsulfatase A deficiency in intact cultured cells using a fluorescent derivative of cerebroside sulfate. AB - A fluorescent derivative of cerebroside sulfate (12-(1-pyrene)dodecanoyl sphingosylgalactosyl-0-3-sulfate (P12-sulfatide) has been synthesized as a potential substrate for the determination of cerebroside sulfatidase (or arylsulfatase A) activity. It was administered into cultured human skin fibroblasts and thereby utilized for the diagnosis of arylsulfatase A deficiency. Cultured skin fibroblasts from normal individuals and healthy persons suffering from a pseudoarylsulfatase A deficiency (PD) degraded the P12-sulfatide, while in cells derived from a metachromatic leukodystrophy (MLD) patient it remained essentially intact. This contrasts with in vitro determinations of enzymatic activity, where the MLD or PD-derived arylsulfatase A exhibit similar deficiency, in spite of a profoundly different clinical course. Administration of the fluorescent sulfatide into the intact cells permitted a sensitive and rapid diagnosis of MLD and its distinction from the PD-phenomenon. This might be of particular importance for cases in which a rapid diagnosis is required and for prenatal diagnosis of fetuses from families afflicted with both MLD and pseudo deficiency mutant genes. PMID- 2885116 TI - Effects of propranolol, atenolol, and chlordesmethyldiazepam on response to mental stress in patients with recent myocardial infarction. AB - Stress testing was carried out by two stressors, mental arithmetic and Sacks Levy's test in randomized sequence, in 64 male patients with a mean age of 51 +/- 7 years in NYHA Classes I or II within 3 months after acute myocardial infarction. The stress profile was obtained after drug withdrawal by continuous recording of electrocardiogram, frontal electromyogram, and peripheral skin temperature and conductance. Blood pressure was measured each minute by cuff. The patients were subdivided into 4 groups of 16 each and were studied in an identical fashion after a 48-h oral treatment with propranolol 120 mg daily, atenolol 100 mg daily, chlordesmethyldiazepam 2 mg daily, or placebo. During stress, signs of myocardial ischemia or pump failure were not observed; minor arrhythmias were recorded. Cardiovascular activation was observed with significant increments (p less than 0.001) in heart rate, systolic and diastolic blood pressures in all 4 groups for both stressors with a slightly greater effect of mental arithmetic; Sacks' test was more effective on the frontal electromyograph response. Following beta blockade the stress profile of heart rate was significantly lower and flattened. The stress profile of blood pressure was also lower, but the reduction in the increment during stress was not significant. No differences were observed in the effects of the two beta blockers; no significant changes were evident in the stress profile of the noncardiovascular psychophysiologic indexes. Stress profiles were not altered by the benzodiazepine. In conclusion beta-blocker agents seem to be more useful than anxiolytic drugs in preventing cardiovascular activation induced by mental stress in patients with recent myocardial infarction. PMID- 2885117 TI - Efficacy of nisoldipine combined with beta-adrenergic-blocking drugs in the treatment of chronic stable angina. AB - A double-blind, placebo-controlled study was performed to assess whether a new calcium antagonist, nisoldipine, in doses of either 5 mg or 10 mg daily, in combination with beta-adrenergic-blocking drugs (combination therapy) was more effective than beta-adrenergic-blocking drugs alone (single therapy) in the treatment of chronic stable angina. Treatments were assessed at two-week intervals, using exercise electrocardiography and patients' anginal diaries. A significant improvement in exercise capacity and reduction in anginal attacks occurred only during nisoldipine (10 mg daily) combination therapy compared with single therapy. Mean exercise time increased from 419 +/- 146 s (single) to 454 +/- 158 s (p less than 0.02) after combination therapy. Exercise time to onset of 1 mm ST-segment depression improved from 326 +/- 145 s (single) to 331 +/- 139 s after combination therapy, although the change was not significant. Mean number of anginal attacks decreased from 21 +/- 22 (single to 15 +/- 19 (p less than 0.01) during combination treatment, with an associated significant reduction in glyceryl trinitrate consumption. Adverse effects during combined therapy were minor and tolerable. Thus patients limited by exertional angina despite beta adrenergic-blocking drugs may obtain supplemental relief of angina and myocardial ischemia with the addition of nisoldipine in a dose of 10 mg daily. PMID- 2885118 TI - Takayasu's disease and bilateral sacroiliitis. AB - A young woman, with HLA B27 negative bilateral sacroiliitis and subsequent Takayasu's disease is described. It has been previously suggested that there is an association between Takayasu's disease and ankylosing spondylitis. We discuss and dispute this association. PMID- 2885119 TI - Hypertrophic osteoarthropathy with Takayasu's arteritis. PMID- 2885120 TI - Radionuclide demonstration of systemic arterial supply to the lung in Takayasu's arteritis. PMID- 2885121 TI - Symptomatic hypothyroxinemia with normal TSH levels in preterm infants. AB - The authors report eight preterm infants with hypothyroxinemia who developed clinical features similar to those described in congenital hypothyroidism: prolonged jaundice, hypoactivity, lethargy, constipation, edema, and hoarse cry. All had low serum thyroxine, normal thyroid stimulating hormone, and normal thyroid binding globulin levels. After exclusion of other causes for the symptoms, thyroid replacement therapy was started, resulting in rapid resolution of symptoms and return to euthyroid status. Follow-up of these infants after cessation of therapy revealed normal growth and development and normal thyroid function. The authors therefore recommend a prospective study to investigate the incidence of hypothyroxinemia, frequency of associated clinical features, and the benefits of thyroid replacement therapy based on a randomized controlled trial. PMID- 2885122 TI - The effects of four beta-adrenoceptor antagonists during modest exercise on plasma ammonia and heart rate. AB - Plasma ammonia and heart rate were measured in normal volunteers before, during and after an exercise test following administration of placebo, propranolol, pindolol, metoprolol and nadolol. Small changes in plasma ammonia occurred during exercise after placebo. However, all four beta-adrenoceptor antagonists produced considerably greater rises. This effect was most marked after propranolol with the response to pindolol, metoprolol and nadolol being similar and intermediate between placebo and propranolol. Resting heart rate was reduced by all the beta adrenoceptor antagonists except pindolol. Exercise induced changes in heart rate were significantly reduced to a similar degree by all the beta-adrenoceptor antagonists. PMID- 2885123 TI - [Comparison of the effectiveness and tolerance of a new beta-2 stimulant (broxaterol) vs. salbutamol in patients with chronic obstructive bronchopneumopathy]. PMID- 2885124 TI - Dental injuries among Norwegian soccer players. AB - The incidence and type of dental injuries among Norwegian soccer players were assessed according to the files of the Norwegian Soccer Association. In 1979-83 a total of 7319 injuries were reported. Approximately 20% (1267) were dental injuries. In every fifth case the expenses for necessary dental treatment exceeded the maximum compensation from the insurance company. The majority of the injuries occurred among male players (96.5%). Also the relative frequency of dental injuries was higher in men than in women. The prevalence of dental injuries was highest in the top division, and decreased gradually down through the divisions. Goalkeepers seemed to be more susceptible to injuries than did the other players. Uncomplicated crown fracture of maxillary front teeth was common and accounted for 45% of all dental injuries. PMID- 2885125 TI - Characterization of cholinesterase of muscularis muscle of Bufo marinus. AB - We have characterized the cholinesterase (ChE) of muscularis muscle of Bufo marinus by selectively using specific inhibitors of acetylcholinesterase and pseudocholinesterase and observing susceptibility to inhibition when substrate is present in excess. The ChE activity in this preparation due to acetylcholinesterase (AChE) and pseudocholinesterase (BuChE) was 90 and 10%, respectively. The optimum temperature and pH for the ChE were 38 degrees C and 7.4, respectively and the excess substrate inhibition was noted above a pS of 2.6. The Km for acetylthiocholine (ASCh) was 0.76 X 10(-4) M. PMID- 2885126 TI - Neuromuscular synaptic transmission in Limulus polyphemus--I. Actions of aspartate, glutamate and the natural transmitter. AB - Aspartate and glutamate were examined as excitatory transmitter candidates for the tibia flexor muscle of the chelicerate arthropod, Limulus polyphemus. Bath application of aspartate or glutamate caused dose-dependent depolarizations of Limulus muscle fibers and contractions of the whole muscle. Glutamate was about 10 times more potent than aspartate. Aspartate and glutamate depolarizations were associated with a conductance increase in muscle fibers, although aspartate depolarizations were dependent on external sodium, while glutamate depolarizations persisted in the absence of sodium. Although the Limulus excitatory postsynaptic potential (epsp) was associated with a conductance increase the ionic basis of the epsp could not be determined. If, however, the Limulus epsp, like other arthropod epsps, is sodium-dependent then the sodium dependence of the aspartate depolarization is consistent with the action of the natural excitatory transmitter. The sodium-independence of glutamate action, however, is not consistent with generally accepted models of arthropod neuromuscular transmitter action. The rank order of potency for amino acid agonists indicates that the Limulus neuromuscular junction is pharmacologically very similar to other arthropod junctions which are well-accepted to be glutamatergic. Pentobarbital reversibly attenuated the amplitudes of the epsp and aspartate and glutamate depolarizations, and it was found to be the only useful antagonist in Limulus. PMID- 2885127 TI - Neuromuscular synaptic transmission in Limulus polyphemus--II. Release of amino acid putative transmitters from the neuromuscular preparation. AB - High-performance liquid chromatography with fluorescence detection was used to assay the release of putative amino acid transmitters from the Limulus neuromuscular preparation. Motor axon stimulation increased the concentrations of aspartate, glutamate and eight other amino acids in fluid bathing the neuromuscular preparation. Pentobarbital, which attenuates the excitatory postsynaptic potential of Limulus muscle, was used to block both synaptic activation of muscle fibers and any amino acid release that may have resulted from this activation. Stimulus-induced release of glutamate and five other amino acids was blocked by pentobarbital, while release of aspartate and three other amino acids was unaffected; a result which suggests that the latter group of amino acids was released presynaptically. Aspartate is the only physiologically active compound in this group. Consideration is given both to the difficulties involved in interpreting sites of amino acid release and to the problem of using pentobarbital as a presumed postsynaptic antagonist. The evidence concerning the relative merits of either aspartate or glutamate as the natural excitatory transmitter at the Limulus neuromuscular junction is discussed. PMID- 2885128 TI - Hematology, blood chemistry and selenium values of captive pronghorn antelope, white-tailed deer and American bison. AB - Pronghorn were observed to have a significantly higher whole blood selenium concentration than either the white-tailed deer or bison. Pronghorn colloid values were significantly less than those of the bison, and approached statistical significance for the white-tailed deer. Differential white blood cell counts for the white-tailed deer were markedly different from those of the pronghorn and bison. The American bison had significantly higher cortisol values and lower T3 values than either the white-tailed deer or pronghorn. PMID- 2885129 TI - The effect of feeding endophyte infected tall fescue seed on reproductive performance in female rats. AB - Female Sprague-Dawley rats (Rattus norvegicus) were randomly assigned to diets containing mixtures of rat chow and tall fescue (Festuca arundinacea) seed with 0, 5, 10, 20 and 40% infection levels of Acremonium coenophialum to assess the effect of the diets on the reproductive potential of rats. Rats fed 40% infected seed had decreased body weight, decreased mean percent body weight of uteri, failed to maintain normal estrous cycles and were unable to become pregnant. Animals fed a diet of 20% infected fescue seed had extended estrous cycles. There were no significant differences among the 0, 5 and 10% dietary treatments. PMID- 2885130 TI - Effect of water-soluble fraction of Cook Inlet crude oil on swimming performance and plasma cortisol in juvenile coho salmon (Oncorhynchus kisutch). AB - Swimming performance of juvenile coho salmon decreased and plasma cortisol increased, following 48-hr exposure to the water-soluble fraction (WSF) of Cook Inlet crude oil at 75% of the LC50. Exposure to 25 and 50% of the LC50 did not significantly reduce swimming performance. Plasma cortisol concentrations were highest in fish exposed to both the combined stress of WSF exposure and of forced swimming in a stamina tunnel. PMID- 2885131 TI - The effects of selenium on the distribution of mercury in the organs of the black bullhead (Ictalurus melas). AB - Following i.p. mercuric chloride injections, the mercury was deposited primarily in the kidneys. Simultaneous selenium injections prevented mercury induced osmoregulatory failure even though selenium strongly promoted the movement of mercury to the kidneys and its deposition in an approximate 1:1 mercuric selenite ratio. Whole-body retention of mercury was not altered by simultaneous subcutaneous injections of sodium selenite. PMID- 2885132 TI - Circadian rhythms and contents of catechols in different brain structures, peripheral organs and plasma of the Atlantic cod, Gadus morhua. AB - Diurnal variations in the concentrations of the catechols (CA) L-DOPA (LD), dopamine (DA), noradrenaline (NA), adrenaline (A) and DOPAC were determined in different brain parts, peripheral organs and plasma of the Atlantic cod, Gadus morhua, over a 24-hr period of artificial standard laboratory conditions and natural light (dark interval: 22.11-04.14). Three to four fishes were captured at 3-hourly intervals and killed by breaking their necks. The organs were dissected out and prepared using the alumina extraction procedure and subsequently analysed in an HPLC-system with electrochemical detection. In the brain structures (telencephalon, optic lobes, medulla oblongata + pons and hypothalamus), the CA levels showed a bimodal pattern with peaks at 16.00-19.00 and 07.00. The catecholamines (CAM) DA, NA and A exhibited the same pattern in the spleen, while NA and A in the heart and NA in plasma varied in a trimodal rhythm with peaks at 19.00, 01.00-04.00 and 07.00. The distribution of CAs and ratios of CAMs in the various brain structures, peripheral organs and plasma are given. The mean concentrations were calculated from the mean of eight groups of cod, taken over a 24-hr period. The results obtained are discussed in relation to the activity pattern of the cod and the differences in CA levels and rhythms between central structures, peripheral organs and plasma of the cod are discussed in relation to other studies on CA levels and rhythmic variations of CAs in related animals. PMID- 2885133 TI - Antagonistic actions of prostaglandins E2 and F2 alpha on the isolated lungs of the frog, Rana esculenta L. AB - Isolated lungs of the frog, Rana esculenta L., when incubated in amphibian Ringer solution for 30 min, produced a prostaglandin E2-like substance (27.1 +/- 3.8 ng/g w.w.), as determined by bioassay on the isolated rat stomach strip. The release of PGE2-like substance from skin, heart and bowel is also reported. The activity of synthetic prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) on the muscular contractility of frog isolated lungs was investigated: PGE2 and PGF2 alpha relaxed and contracted respectively in a dose-dependent manner this preparation, a result similar to that obtained in mammals. PMID- 2885134 TI - Paraquat as an agent affecting antioxidant enzymes of common carp erythrocytes. AB - The effects of paraquat on the superoxide dismutase, catalase, glutathionine peroxidase activities and lipid peroxidation at different times of paraquat exposure of Cyprinus carpio morph L. erythrocytes were studied. Typical characteristics were observed in the changes of the enzyme activities of the erythrocytes after exposure to paraquat. The haemoglobin concentration of common carp haemolysates was decreased by exposure to paraquat. PMID- 2885135 TI - In vitro studies of the effects of naloxone on the root potentials in the frog spinal cord: enkephalin-like effect on the recurrent presynaptic inhibition. AB - Specific binding of [3H]naloxone was demonstrated in the frog spinal cord. In isolated and perfused frog spinal cord, naloxone increased the spontaneous discharges of the ventral root. Naloxone decreased the ventral root-dorsal root potential (VR-DRP) in a dose-dependent manner, and inhibited presynaptic inhibition of the ventral root reflex. Methionine-enkephalin also decreased the VR-DRP, and naloxone partially antagonized this effect. These results suggest the existence of enkephalinergic control of spinal motor activities and that naloxone has a partial agonistic effect in the frog spinal cord. PMID- 2885136 TI - Correlation of myosin light chain phosphorylation and gamma aminobutyric acid receptors in Ascaris suum muscle. AB - Four different muscle relaxants were compared as to their effects on tonic Ascaris suum muscle to: physiological activity, intracellular response to regulatory light chain phosphorylation, and receptor pharmacology. Perfusion of Ascaris suum muscle with each relaxant, gamma-aminobutyric acid, avermectin, piperazine and chlorpromazine resulted in a dose-dependent loss of muscle tone. Comparison of intracellular effects indicated that gamma-aminobutyric acid and avermectin perfusion initiated an increase in the levels of dephosphorylated regulatory light chain while piperazine increased first site phosphorylation and chlorpromazine increased second site phosphorylation. Receptor pharmacology studies were used to compare the actions of gamma-aminobutyric acid and piperazine. It was found that bicuculline-methiodide and picrotoxin inhibited the effects of gamma-aminobutyric acid in a dose-dependent manner, but these drugs had no effect on muscle relaxation stimulated with piperazine. PMID- 2885137 TI - Deltamethrin-induced changes in synaptosomal transport of 3H-epinephrine in the squid optic lobes. AB - In fresh synaptosomal preparation from the squid optic lobe 3H-epinephrine transport was significantly affected by deltamethrin at greater than 10(-9) M. Under the experimental conditions such an effect of deltamethrin manifested as either a reduction (at nondepolarized state) or an increase (at depolarized state) in the final level of 3H-epinephrine accumulated in the synaptosomes. Only a part of such a deltamethrin effect was due to its effect on the sodium channel. The remainder of the deltamethrin effect was strongly influenced by agents or treatments which are known to influence internal Ca2+ concentration, suggesting a possible involvement of Ca2+ regulatory mechanisms in the process of stimulation of transmitter release by deltamethrin. PMID- 2885138 TI - Uptake of gamma-aminobutyric acid by catfish brain. AB - Using homogenates of catfish whole-brain in an isotonic medium, we observed an accumulation of [3H]GABA that was temperature-sensitive and was dependent on the presence of sodium ions, the optimum concentration of which was 75 mM. A kinetic analysis showed that the [3H]GABA uptake mechanism became saturated with increasing GABA concentrations. A high-affinity system, only, was evident whose Km was calculated as 12 microM. Four structural analogues of GABA were found to be competitive inhibitors of uptake, and Ki values were determined. Nipecotic acid (Ki = 1.8 microM) and guvacine (Ki = 3.9 microM) were the most potent compounds, however 2,4-diaminobutyric acid (Ki = 8.9 microM) and beta-alanine (Ki = 55 microM) also had an effect. The characteristics of the uptake mechanism in catfish brain that we have studied are similar to those reported for uptake by mammalian brain except that in the latter, both a high- and a low-affinity transport processes are present. Our data, taken together with what is already known, strongly suggest that the biochemistry of the GABA system in lower vertebrates does not differ significantly from that in mammals. PMID- 2885139 TI - Electrocardiographic alterations induced by AGEPC in Wistar rats in relation to its hypotensive and hematologic effects. AB - AGEPC administration into Wistar rats caused no remarkable thrombocytopenia, slight decrease of the percent count of PMNs in whole blood accompanied by anequal leukocytopenia and a transient increase in hematocrit, due to fluid extraversion. Apart from the dramatic fall in blood pressure caused by AGEPC, relatively sinus bradycardia was recorded at doses over 6 micrograms/kg b.w. S-T segment elevation, mainly evident in II, III and AVF leads, was also recorded within the first minutes after AGEPC administration, at doses over 1 microgram/kg b.w. At lethal doses, various degrees of A-V block resulting in complete A-V block with idioventricular rhythm, or injury pattern resulting in ventricular fibrillation or ventricular flutter, were recorded. At sublethal doses no arrhythic manifestations were recorded, while S-T segment elevation upward inversion became gradually normal. PMID- 2885140 TI - Radioligand binding characterization of beta-adrenergic receptors in the protozoa Trypanosoma cruzi. AB - A direct radioligand binding technique utilizing the beta-adrenergic antagonist [3H]dihydroalprenolol was employed in the identification and characterization of Trypanosoma cruzi beta-adrenergic receptors. [3H]DHA binding was saturable (Bmax = 1.5 pmol/10(6) cells) with an apparent equilibrium dissociation constant (Kd) of 127 nM. Binding of [3H]DHA was displaced by propranolol in a concentration dependent manner. The relative potency order of adrenergic ligands in displacing [3H]DHA binding was: propranolol greater than or equal to alprenolol greater than epinephrine. 5-Hydroxytryptamine, phentolamine and catechol had no effect. The experimental results support the suggestion that beta-adrenergic receptors are present in the pathogenic protozoa Trypanosoma cruzi. PMID- 2885141 TI - Sequestration of environmental cadmium by metallothionein in the roach (Rutilus rutilus) and the stone loach (Noemacheilus barbatulus). AB - Two species of coarse fish that are relatively resistant to cadmium poisoning were exposed to sub-lethal concentrations of the metal in their aquarium water. Thus, roach were exposed to cadmium concentrations between 30 and 500 micrograms/l for periods of 14-70 days whereas stone loach were exposed to 1250 micrograms Cd/l for 21-77 days. Under all conditions of exposure, it was found upon analysis of the major organs of accumulation of cadmium in the two species that the toxic metal was sequestered by a single isoform of metallothionein. The amino acid compositions of roach and stone loach metallothionein were determined and found to be similar to those reported for other piscine metallothioneins. The two proteins were found to contain Cd:Zn:Cu in approximate ratios of 4:1:2 per mole of protein. The sequestration of Cd by metallothionein in the two resistant species of fish is contrasted with the situation observed previously in a cadmium sensitive species, the rainbow trout. PMID- 2885142 TI - Nyctohemeral rhythm in melatonin response to isoproterenol in vitro: comparison of rats and Syrian hamsters. AB - The in vitro response of melatonin synthesis was assessed by incubation of individual whole pineal glands for 4 hr without or with different concentrations of isoproterenol in the medium. Pineals were taken either at the end of the 14-hr light phase (day), or at 6 1/2 hr into the 10-hr dark phase (night) after a 30 min exposure of the animals to light just before sacrifice at night. The response was greater in pineals taken at night than in those taken at the end of the light phase in rats, but was absent at the end of the light phase in Syrian hamsters. Hamster pineals taken at night responded, though higher isoproterenol concentrations were required than in the rats. Unresponsiveness of hamster pineals during the day may explain previous failure of isoproterenol administration to stimulate pineal MEL content in this species. PMID- 2885143 TI - Biogenic amines and their metabolites in Trichostrongylus colubriformis, a nematode parasite of ruminants. AB - The following biogenic amines (BA) and BA metabolites were identified via HPLC in homogenates prepared from adults of Trichostrongylus colubriformis (Nematoda) recovered from the intestines of goats: N-acetyldopamine, DOPA, dopamine, epinephrine, epinine, 5-hydroxyindoleacetic acid, 4-hydroxy-3-methoxy phenylglycol, 3-(p-hydroxyphenyl) proprionic acid, metanephrine, O-methyl-DOPA, 3 methoxytyramine, norepinephrine, normetanephrine, octopamine, p-hydroxymandelic acid, serotonin, synephrine, tyramine and vanillylmandelic acid. The mean concentrations of these compounds in groups of worms collected from different goats did not differ significantly with sex, but between the groups variance was high with probable components of both host and nematode origin. PMID- 2885144 TI - Myocardial levels of calcium, glycogen and triglycerides in ethanol-fed turkey poults treated with allopurinol. AB - Effect of allopurinol treatment on myocardial levels of calcium, glycogen and triglyceride and on plasma levels of triglyceride was evaluated in turkey poults during a period of chronic ethanol consumption and following a period of ethanol abstinence. Allopurinol treatment had no significant effect on myocardial levels of calcium. Allopurinol treatment plus abstinence was slightly more effective than abstinence alone in restoring myocardial levels of glycogen and triglyceride and plasma levels of triglyceride in ethanol-fed poults to that seen in control poults. PMID- 2885146 TI - Environmental and injected cadmium are sequestered by two major isoforms of basal copper, zinc-metallothionein in gibel (Carassius auratus langsdorfi) liver. AB - Gibels were exposed to cadmium in their aquarium at a concentration of 10 micrograms Cd/l for up to 39 weeks. Distributions of cadmium, copper and zinc in the liver soluble fraction were determined along with sulfur by high performance liquid chromatography-inductively coupled argon plasma-atomic emission spectrometry. Cadmium was sequestered by the two major isoforms of gibel metallothionein as in the case of cadmium injected intraperitoneally into gibel. Several peaks with cadmium, copper, zinc and sulfur were observed other than the two major isoforms and their relative ratios were different between the control and cadmium-exposed fishes. PMID- 2885145 TI - Tissue distribution of acebutolol in mature normotensive and stroke-prone spontaneously hypertensive rats. AB - Tissue distribution of acebutolol was studied in 33-week-old normotensive (WKY) and Okamoto stroke-prone (SHR-SP) rats, 30 min after an i.v. administration, by using 14C-acebutolol. Plasma level of acebutolol was higher in WKY than in SHR SP. Aorta, kidney, liver and muscle radioactivity/plasma radioactivity ratios were higher in SHR-SP than in WKY. The brain/plasma radioactivity ratio was very low and similar in the two groups. The drug distribution was the same in the two groups except in medulla + corpus trapezoides where drug concentration was greater in SHR-SP. These results, compared with previous ones, show an age related evolution in pathological state in SHR-SP. They point out a specific concentration of the beta-blocking drug in a defined part of the brain, namely medulla + corpus trapezoides. PMID- 2885147 TI - Effects of fasting and refeeding on vasoactive intestinal peptide binding to rat blood mononuclear cells. AB - The effect of acute and chronic starvation on vasoactive intestinal peptide (VIP) binding to rat blood mononuclear cells was studied. A short-term (1 day) fasting period did not induce significant changes in VIP binding. Longer periods of fasting (3 and 5 days) elicited an increase in VIP binding. This increase was due to an increase in affinity of both the high and the low affinity binding sites rather than to changes in binding capacity. Refeeding of fasted animals resulted in a decrease in VIP binding, reaching similar values to those of the control groups. PMID- 2885149 TI - [A message from the Calvary Hospital: an impression on the 4th International Oncology Nursing Conference]. PMID- 2885148 TI - Pharmacology of putative glutamate receptors from insect skeletal muscles, insect central nervous system and rat brain. AB - Binding of [3H]glutamate to housefly brain and honeybee brain and thoracic muscle membranes as well as to the American cockroach nerve cord was measured in Na+ free Tris-citrate buffer, 2.5 mM CaCl2, pH 7.4. The dissociation constants (KDS) ranged from 0.16 to 1.36 microM, and thoracic muscles had 2-4-fold higher density of receptors than brain tissue. The potent inhibitors of housefly brain binding were in decreasing order of effectiveness: L-glutamate greater than L-aspartate = L-cysteate = ibotenate greater than quisqualate greater than L-homocysteate greater than L-APB greater than L-APV greater than NMDA greater than D-APB greater than D-glutamate, with no inhibition by 100 microM of GDEE, dihydrokainate, D-APV, D-homocysteate or D-aspartate. The drug specificity of [3H]glutamate binding sites in housefly brain was generally similar to that of binding sites in housefly muscle, except that the former had a slightly higher affinity for L-APB, L-homocysteate and NMDA. [3H]Glutamate binding to insect tissues differed in its drug sensitivity from binding to rat brain. Binding to insect membranes was much less sensitive to L-APB, D-APB, APV, homocysteate, L cysteate, quisqualate and ibotenate. However, the insect binding site was much more stereoselective for the L than D isomers of glutamate and aspartate, while the rat brain site was more stereoselective for APB. It is suggested that the observed [3H]glutamate binding to insect tissue is not to NMDA or kainate receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885150 TI - Terfenadine does not inhibit non-immunologic contact urticaria. AB - To investigate the mechanisms of non-immunologic contact urticaria (NICU), the effect of 120 mg of terfenadine (H1-antagonist) on contact reactions to methyl nicotinate, diethyl fumarate, benzoic acid, cinnamic acid, cinnamic aldehyde and dimethyl sulfoxide was studied in 20 subjects. Erythema and edema were observed visually, and the changes in the skin blood flow were monitored with laser Doppler flowmetry. Terfenadine did not have any significant inhibitory effect on erythema or edema from 6 contact urticariants tested, but it inhibited erythema and edema of prick test reactions to histamine. Non-specific histamine release from mast cells does not seem to be the mechanism of NICU from these substances. PMID- 2885151 TI - Highly polymorphic DNA sequences in the distal region of the long arm of human chromosome 18. AB - Highly polymorphic repeated DNA sequences were detected at the end of the long arm of human chromosome 18 by a recombinant DNA probe containing 56 bp of human DNA (pERT25). This was shown by hybridization of pERT25 to DNA from a panel of human X rodent somatic cell hybrids, by dot blot hybridization to flow-sorted human chromosomes, and by in situ hybridization to metaphase chromosomes. The high degree of polymorphism detected by this 18q DNA fragment makes it potentially useful for various applications, including investigations into the genetics of trisomy 18 (Edwards syndrome), linkage studies, and paternity testing. PMID- 2885152 TI - Exclusion of linkage of loci on chromosome 19 with multiple endocrine neoplasia, type 2. AB - Linkage between seven loci on chromosome 19 and multiple endocrine neoplasia type 2a (MEN2A) was examined in a single large Swedish pedigree. A total of 50 cM was excluded from the male genetic map by pairwise analysis and an estimated 63 cM by multipoint analysis. Using existing data on the likelihood of different marker marker distances and taking into account current exclusions on other chromosomes, the probability that the gene for MEN2A segregating in this pedigree could still be located on chromosome 19 is approximately 0.28%. PMID- 2885153 TI - Mapping of alpha-spectrin on distal mouse chromosome 1. AB - DNAs from different strains of inbred mice and feral Mus spretus were found to exhibit restriction fragment length polymorphisms (RFLP) when hybridized with a probe prepared from a c-DNA clone of the mouse alpha-spectrin (Spna-1) gene. Studies of five recombinant inbred strains and (C57BL/6 X M. spretus) F1 X C57BL/6 backcross mice demonstrated that these RFLPs were allelic and that Spna-1 is closely linked to Ly-9 and Ly-17 on the distal region of chromosome 1. PMID- 2885154 TI - The anonymous RFLP locus D11S16 is tightly linked to catalase on 11p. PMID- 2885155 TI - The effect of theophylline and beta 2 agonists on airway reactivity. AB - Increased airway responsiveness occurs in asthma, chronic bronchitis, cystic fibrosis, and other diseases. Theophylline and beta 2 agonists commonly are used as maintenance therapy for symptoms associated with the increased responsiveness. Both drugs can reduce airway responsiveness to a variety of provocational stimuli. With currently used dosing regimens, theophylline appears to produce relatively constant levels of effect on airway responsiveness and clinical efficacy around the clock, while inhaled beta 2 agonists appear to have insufficient effects at the end of longer dosing intervals. Improved dosing strategies for beta 2 agonists may improve the efficacy of these agents in the future. PMID- 2885156 TI - Theophylline as a bronchodilator in COPD and its combination with inhaled beta adrenergic drugs. AB - The bronchodilating action of theophylline in COPD has been examined, with emphasis on its combined use with inhaled beta 2 agonists. The suggestion is made that failure to recognize the nonlinearity of the dose-response curves for bronchodilators has resulted in underestimating their combined action. Recent studies suggest that systemic theophylline has somewhat different actions on the airways in COPD than inhaled beta agonists, and that more bronchodilation may be possible when the two are used together than large doses of either one. By analogy, with asthma the suggestion is also made that the addition of theophylline is also likely to provide a more constant bronchodilation, reducing peak-trough variations in flow. The most complete clinical comparison to date suggests that, in currently sanctioned doses, a regimen containing both theophylline and an inhaled beta 2 agonist provides significantly greater bronchodilation than either drug alone, with fewer patient withdrawals. Further carefully designed studies are needed to resolve this issue, and particularly, to identify those patients who will derive the greatest benefit from a combined regimen. PMID- 2885157 TI - Puerarin beta-adrenergic receptor blocking effect. PMID- 2885159 TI - Epidemiology of lymphatic filariasis. AB - Human lymphatic filariasis is caused mainly by Wuchereria bancrofti, Brugia malayi and Brugia timori. Of the estimated 90.2 million people infected, more than 90% have bancroftian and less than 10% brugian filariasis. The distribution and transmission of the disease are closely associated with socioeconomic and behavioural factors in endemic populations. Urban W. bancrofti infection, as seen in South-East Asia, is related to poor urban sanitation, which leads to intense breeding of Culex quiquefasciatus, the principal vector. Rural strains of W. bancrofti are transmitted primarily by Anopheles spp. and Aedes spp. mosquitoes. Brugian filariasis is mainly a rural disease transmitted by Mansonia, Anopheles and Aedes spp. mosquitoes. The periodic form of B. malayi is principally a human parasite, whereas the subperiodic form is zoonotically transmitted in some countries. The control of filariasis has relied on chemotherapy, vector control and reduction of human-vector contact. Although eradication of W. bancrofti and periodic B. malayi can be achieved, it is possible only to reduce transmission of zoonotic subperiodic B. malayi in some areas. A rational approach to control should consider ecological, socioeconomic and behavioural factors and, where feasible, integrate control programmes into the delivery system for primary health care. PMID- 2885158 TI - Characterization of the filarial genome. AB - Filarial parasites are just beginning to be studied at the genetic level. The potential of recombinant DNA technology for identifying parasite genes that are important in the pathogenesis of filarial disease or for the survival of the parasite is enormous. Work in several laboratories has already identified genes which encode ribosomal RNAs, as well as highly repeated DNA sequences that can be used as diagnostic probes. In addition, new methods to separate chromosomes will allow the physical mapping of parasite genes without the requirement for classical genetic analysis, which would be difficult in filariids. PMID- 2885160 TI - The expression of stage-specific embryonic antigen 1 in the noncancerous colorectal epithelia of familial polyposis coli. AB - The epithelial expression of carbohydrate antigen, stage-specific embryonic antigen 1 (SSEA-1) was examined immunohistochemically in noncancerous specimens from patients with familial polyposis coli, and compared with the colorectal epithelia from patients with sporadic colorectal cancer. In mucosa remote from carcinoma of sporadic cases, SSEA-1 was expressed only faintly in the lower crypts. In mucosa adjacent to carcinoma of sporadic cases, SSEA-1 was expressed not only in the lower crypts but also in the upper crypts. These results corresponded to those observed in the authors' previous study. In the flat mucosa of familial polyposis coli cases, SSEA-1 was detected not only in the lower crypts, but also in both upper crypts and the surface epithelium in contrast with the flat mucosa of sporadic cases. The staining pattern in the upper crypts of the flat mucosa of familial polyposis coli cases was very similar to that of the mucosa adjacent to carcinoma of sporadic cases, but was stronger and more diffuse in the surface epithelium. In microscopic adenomas, SSEA-1 was expressed diffusely. These results demonstrate that the flat mucosa of patients with familial polyposis coli shows preneoplastic changes similar to those in the mucosa adjacent to carcinoma of sporadic cases, and that SSEA-1 is related to adenoma formation in the early stage of carcinogenesis in the colorectum. In addition, the results suggest that immunohistochemical studies of flat mucosa may be useful for the early detection of high-risk individuals in a familial polyposis coli family. PMID- 2885161 TI - Plasma immunoreactive somatostatin response to arginine after glycemic control with continuous subcutaneous insulin infusion in type I diabetics. AB - The effects of 3 wk of near normoglycemia by continuous subcutaneous insulin infusion (CSII) on plasma immunoreactive somatostatin (IRS) responses to arginine (0.5 g X kg-1 X 30 min-1) in seven patients with insulin-dependent diabetes mellitus (IDDM) were compared with the same patients in poor glycemic control during conventional insulin therapy (CIT) and with seven normal controls. After 3 wk of CSII treatment, mean daily blood glucose and HbA1 decreased to mean (+/- SE) values of 129 +/- 6 mg/dl and 8.0 +/- 0.1%, respectively. Plasma free-insulin levels in IDDM patients 30 min before a meal during CSII were significantly higher than those during CIT or in normal controls. Fasting mean plasma IRS levels of the IDDM patients during CSII (7.3 +/- 1.4 pg/ml) were not different from those during CIT (8.4 +/- 1.3 pg/ml) and in normal controls (5.9 +/- 0.8 pg/ml). Arginine elicited a rise in plasma IRS during CIT in all seven IDDM patients during CIT and in the normal controls, with peak values of 18.2 +/- 4.1 and 12.5 +/- 1.8 pg/ml, respectively. However, no significant increase in plasma IRS was observed in all seven IDDM patients during CSII. The integrated values of plasma IRS during the arginine-infusion study of the IDDM patients treated with CIT were significantly higher than those of the normal controls. The increased integrated values of plasma immunoreactive glucagon response to arginine observed during CIT became normalized after CSII. These results suggest that glycemic control with CSII in IDDM patients suppresses the increased plasma IRS response to arginine that occurs during CIT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885162 TI - Drug-induced pulmonary disease. AB - Administration of more than 40 separate pharmacologic agents has been associated with some form of pulmonary toxicity. This problem is becoming more significant every year. Occasionally, effective modes of therapy must be withdrawn because of undesirable pulmonary side effects, putting patients at risk for potentially lethal diseases. Pulmonary parenchymal damage due to drugs is an especially troublesome problem because irreversible pulmonary disease may occur. Mechanisms of pulmonary parenchymal tissue damage by drugs are unclear. It appears that some drugs induce direct tissue injury in addition to indirect tissue damage through amplification of pulmonary inflammation; other drugs cause pulmonary alterations solely through indirect mechanisms. Common clinical syndromes associated with drug-induced pulmonary parenchymal disease include pneumonitis/fibrosis, hypersensitivity lung disease, and noncardiogenic pulmonary edema. Less common patterns of pulmonary parenchymal injury by drugs include bronchiolitis obliterans and a pulmonary renal syndrome. Risk factors for pulmonary injury due to pharmacologic agents are partially defined but not entirely understood. To date, there are no adequate tests for early detection of pulmonary damage by drugs, although research into this area is active. This review discusses mechanisms and clinical features of drug-induced pulmonary parenchymal injury to aid the clinician in recognizing and understanding these syndromes. PMID- 2885163 TI - DNA sequence and regional assignment of the human follicle-stimulating hormone beta-subunit gene to the short arm of human chromosome 11. AB - A human genomic DNA fragment in phage lambda containing FSHB, the gene for the beta-subunit of human follicle-stimulating hormone (FSH-beta), was analyzed and the nucleotide sequence of the region of the clone encoding FSH-beta was determined. A subclone of the lambda phage containing 67% of FSH-beta coding sequence was used as hybridization probe to determine the human chromosomal location of FSHB. A panel of mouse-human somatic cell hybrids containing reduced numbers of human chromosomes was screened with the FSHB probe; complete cosegregation of FSHB with human chromosome 11 was observed in all 26 cell hybrids tested. Analysis of a set of cell hybrids containing translocated derivatives of chromosome 11 further localized FSHB to the human chromosome region 11p11.2----11pter. A Hind III restriction fragment length polymorphism (RFLP) detected by another subclone of the lambda phage containing FSHB now provides a genetic marker for this region of the human genome. PMID- 2885165 TI - Two more hypnotics added to the 'White List'. PMID- 2885166 TI - [Alzheimer's disease]. PMID- 2885164 TI - Rat calmodulin cDNA. AB - We report the isolation of a clone encoding calmodulin from a rat brain cDNA library; genomic clones were also isolated and partially characterized. The derived amino acid sequence has 100% homology to the published mammalian protein sequences. In rat, we identify two major RNA species of approximately 2.2 and 0.75 kb in length by RNA blot analysis. Furthermore, the mRNA is highly enriched in brain tissue, compared to liver or kidney. A variant (GATAAA) of the putative poly(A) addition signal is observed at the 3' end of one of the mRNA species. PMID- 2885167 TI - [Beta blockers in situational anxiety states]. PMID- 2885168 TI - Esmolol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. AB - Esmolol is a relatively cardioselective beta-adrenoceptor antagonist. Since esmolol is rapidly metabolised by blood-borne esterases, it has a very short half life (about 9 mins) and a short duration of action. In this respect esmolol is unique amongst currently available beta-adrenoceptor antagonists, and it is anticipated that it will be particularly useful in critical care situations where administration by continuous intravenous infusion should permit a level of control over beta-adrenoceptor antagonism that has previously been unattainable. In perioperative settings, esmolol attenuates tachycardia induced by a variety of surgical stimuli such as endotracheal intubation, sternotomy and aortic dissection, suggesting a clinical use of the drug to prevent potentially serious complications in surgical patients with cardiovascular disease. Additionally, clinical studies have shown that titrated dosages of esmolol achieved therapeutic response rates of 66 to 79% in patients with supraventricular tachyarrhythmias, which favourably compared with response rates achieved with propranolol. In most of these patients esmolol produced a reduction in ventricular rate which was well maintained during infusion but disappeared within 30 minutes following esmolol withdrawal. Preliminary studies involving small numbers of patients have reported that esmolol exerts significant antihypertensive effects in patients with postoperative hypertension, and beneficial effects in patients with myocardial ischaemia and infarction, but support for these results is required from additional large, well-controlled studies. Esmolol has been generally well tolerated, and although hypotension has occurred in up to 44% of patients it resolved during or soon after the infusion of esmolol. Thus, esmolol is the first titratable beta-adrenoceptor antagonist able to be rapidly 'switched on' and 'off', a property that is expected to offer a major contribution to safety in critical care patients requiring beta-adrenoceptor antagonism for short durations. PMID- 2885170 TI - The role of arachidonic acid metabolites in gastrointestinal homeostasis. Biochemical, histological and clinical gastrointestinal effects. AB - Metabolites of arachidonic acid have a broad range of physiological functions in the gastrointestinal tract, and seem to be involved in certain disturbances of gastrointestinal integrity and function. Prostaglandins inhibit gastric acid secretion, apparently via an adenylate cyclase-linked receptor, and also stimulate bicarbonate and mucus production by alternative mechanisms. These are all beneficial in treating gastroduodenal ulceration. Moreover, clinical studies have revealed deficient prostaglandin synthesis in the gastric and duodenal mucosa of patients with gastrointestinal ulcers, which suggests that endogenous prostaglandins have a protective role in the gastrointestinal tract. In animal studies, prostaglandin analogues have been shown to protect the gastric mucosa from damage induced by various potent irritants, and this protection seems to involve the deeper layers of the mucosa as well as the epithelium. Indeed, misoprostol and other prostaglandin analogues have proved therapeutically effective in treating gastroduodenal ulceration. Prostaglandins also influence intestinal motility and fluid movement. Prostaglandin E derivatives generally relax circular smooth muscle, contract longitudinal smooth muscle and increase fluid secretion into the intestinal lumen. As a result of these effects, prostaglandins may cause diarrhoea. There is also evidence that prostaglandin synthesis is increased in patients with diarrhoea. Finally, it has been reported that tissue concentrations of prostaglandins are increased in patients with ulcerative colitis, but it is unclear if this is a primary cause, or secondary event. Significantly greater conversion of arachidonic acid to its metabolites was recorded in the mucosa of patients with inflammatory bowel disease compared with the mucosa of healthy subjects. This included a substantial increase in the concentration of leukotriene B4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885169 TI - Terazosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in essential hypertension. AB - Terazosin is a post-synaptic alpha 1-adrenoceptor antagonist with a similar pharmacodynamic profile to prazosin. It differs from prazosin in having a longer duration of action, with an elimination half-life some 2 to 3 times that of prazosin, allowing the convenience of once daily administration. Moreover, its absorption from the gastrointestinal tract is more complete and predictable than that of prazosin which may facilitate dose titration. Terazosin therapy results in a significant reduction in blood pressure in patients with mild to moderate essential hypertension, with little influence on heart rate. The drug is an effective antihypertensive when administered as monotherapy or in combination with a range of antihypertensive agents including beta-blockers, diuretics and combinations of the two. In the few patients with congestive heart failure studied, terazosin produced an increase in cardiac output with a reduction in ventricular filling pressure and systemic vascular resistance, but no studies have been performed to assess the therapeutic potential of terazosin in this indication. Reductions in total plasma cholesterol and low density plus very low density lipoprotein cholesterol fractions have been reported after terazosin therapy, while high density lipoprotein cholesterol concentrations have tended to increase. Should such beneficial changes be confirmed in long term clinical studies they would suggest a therapeutic advantage of terazosin over some other antihypertensive drugs, particularly diuretics, which have been reported to adversely affect the plasma lipid profile. The most common side effects associated with terazosin treatment are dizziness, headache, asthenia and nasal congestion, but these are usually mild and do not require treatment discontinuation. Terazosin is normally administered once daily, starting at a dose of 1 mg/day and gradually titrating upwards as the blood pressure stabilises at each new dose, until blood pressure is adequately controlled or to a maximum dose of 20mg daily. First-dose syncope occurs rarely after terazosin, and can largely be avoided by giving the first dose at bedtime. Thus, terazosin offers a useful alternative to the drugs currently available for the management of mild to moderate essential hypertension either as monotherapy or in combination with other antihypertensive drugs. PMID- 2885171 TI - Sequential expression of OX2 and Thy-1 glycoproteins on the neuronal surface during development. An immunohistochemical study of rat cerebellum. AB - The related neuronal surface glycoproteins, Thy-1 and OX2, are shown here to have a reciprocal pattern of expression during development in rat cerebellum. OX2 appears at axonogenesis, on neuronal cell bodies and their axons. Immunohistochemical staining for this molecule then gradually wanes, and over the same period the cells acquire their first, weak staining for Thy-1. Intense Thy-1 expression occurs during the period of dendritic growth. PMID- 2885172 TI - [Clinical pharmacokinetics of haloperidol decanoate. Comparison with other prolonged-action neuroleptics]. AB - Precise pharmacokinetic data of long-acting neuroleptics: apparent half life (T 1/2), time of peak plasma concentration (Tmax), bioavailability, has been a major contribution to determine optimal dosage of the drug. If the aim of the depot neuroleptic is to obtain a stable plasma concentration of the neuroleptic after I.M. injection of the ester form equivalent to that following oral administration, it is logical to obtain the same pharmacological effect; this is true for haloperidol decanoate. Mean value of T 1/2 of clopenthixol decanoate and haloperidol decanoate are 19 and 21 days, respectively, they thereby justify monthly administration. Flupenthixol decanoate and fluphenazine enanthate should be injected with dosing intervals of 3 and 1 weeks, respectively in respect with their half-lives: 17 and 4 days. Fluphenazine decanoate have a half-life of 14 days, however, the longer time the treatment, the longer the apparent half-life, suggesting to reduce the dose or to enlarge the dosing interval. Optimal dose has been determined from the bioavailability of the oral formulation and the interval between two injections, it averages 15, 20 times the oral daily dose for haloperidol decanoate. A lower conversion factor is frequently used (0.5 to 5 times) for other depot-neuroleptics such as pipotiazine palmitate, fluphenazine enanthate or decanoate; these low factors are not entirely explainable by the low bioavailability of the oral forms and produces more lower plasma concentration than after oral administration. PMID- 2885173 TI - [Efficacy and tolerance of alprazolam and bromazepam in flexible doses. Double blind study in 119 ambulatory anxious patients]. AB - Double-blind study comparing efficacy and safety of alprazolam and bromazepam in 119 ambulatory anxious patients receiving flexible dosage. 119 ambulatory anxious patients (global score on the Hamilton anxiety rating scale between 18 and 35) have been included in this double-blind trial (duration 4 weeks) comparing alprazolam and bromazepam given at flexible dosage. The global score on the Hamilton anxiety rating scale improved by 57.8% and 55.3% for alprazolam and bromazepam respectively. The percentage of therapeutic success according to the psychiatrist and the patient were respectively 82.7% and 79.3% for alprazolam compared to 74.1% and 71.9% for bromazepam. Fewer side-effects were recorded in the alprazolam group (97) than in the bromazepam group (120) and global safety of alprazolam seemed superior (p = 0.07). At trial-end, mean dosage reached 1.70 mg/day for alprazolam and 10.35 mg for bromazepam, but no correlation was found between anxiety intensity and optimal daily dosage used; however, a correlation has been found between the improvement of the overall Hamilton rating scale score and the dosage given (p = 0.02). The overall results suggest that the efficacy/safety ratio is better for alprazolam. PMID- 2885174 TI - Release of dynorphin-like immunoreactivity from rat adenohypophysis in vitro during inhibition of anterior pituitary hormone secretion from individual cell types. AB - LHRH has previously been found to be the only known hypothalamic releasing factor which can specifically stimulate the release of the opioid dynorphin and other proenkephalin B-derived peptides from the rat adenohypophysis in vitro. In the present study the mechanisms that regulate dynorphin release were further characterized. It was examined whether or not dynorphin release from the adenohypophysis in vitro is altered during inhibition of the secretion of various anterior pituitary hormones. Rat anterior pituitary quarters were incubated in vitro and hormone release into the incubation medium was measured by RIAs. Somatostatin, dopamine, T3, dexamethasone, and 5 alpha-dihydrotestosterone were used to inhibit the secretion of GH, PRL, TSH, ACTH/beta-endorphin, or LH/FSH, respectively. GH, PRL, or beta-endorphin release was inhibited without affecting the simultaneous release of dynorphin A-(1-13)-like immunoreactivity (Dyn A1-13 IR). Concentrations of T3, somatostatin, or dopamine which were effective in suppressing the evoked and/or basal release of TSH, GH, or PRL, respectively, produced no effect on Dyn A1-13-IR release caused by high potassium concentration (40 mM) or LHRH (500 pM). The LHRH-induced release of LH and FSH was inhibited by the glucocorticoid dexamethasone or the androgen 5 alpha-dihydrotestosterone. Under these conditions, Dyn A1-13-IR release was also reduced. However, whereas LH release was completely blocked by 5 alpha-dihydrotestosterone, FSH and Dyn A1 13-IR release was reduced only by 50%. The release of FSH and Dyn A1-13-IR in vitro from anterior pituitary glands taken from rats, castrated 3 weeks before, was enhanced to a similar extent (about 2.5-fold); the simultaneous enhancement of LH release was significantly (P less than 0.005) greater (about 5-fold). We conclude that the mechanisms which regulate the release and/or biosynthesis of dynorphin and other proenkephalin B-derived peptides of the adenohypophysis are similar to those of the gonadotropins but different from those of any other anterior pituitary hormone, and may be more closely related with FSH release than LH release. These data support the view that dynorphin of the normal rat adenohypophysis may be localized in at least a subpopulation of gonadotrophs. PMID- 2885175 TI - Sympathetic nerve stimulation versus pancreatic norepinephrine infusion in the dog: 2). Effects on basal release of somatostatin and pancreatic polypeptide. AB - We compared the effects of sympathetic nerve stimulation to that of pancreatic norepinephrine (NE) infusion on pancreatic somatostatin-like immunoreactivity (SLI) and pancreatic polypeptide (PP) secretion in the halothane-anesthetized dog. During electrical stimulation (8 Hz, 1 msc, 10 mA, n = 6) of the sympathetic nerves surrounding the pancreatic artery, the pancreatic SLI output decreased from 827 +/- 340 fmol/min to 231 +/- 47 fmol/min (delta = -596 +/- 217 fmol/min, P less than 0.05) after 5 min, and PP output decreased from 11,972 +/- 374 pg/min to 5,518 +/- 774 pg/min (delta = -6,454 +/- 1,932 pg/min, P less than 0.02) after 3 min of stimulation. Arterial SLI or PP levels did not change. Sympathetic nerve stimulation also decreased pancreatic blood flow and increased pancreatic venous NE levels. To determine whether the NE, released locally during sympathetic nerve stimulation, is responsible for this inhibition of pancreatic SLI and PP outputs, exogenous NE was infused into the pancreatic artery at three different dose levels. The low dose of 12 ng/min (n = 6) increased pancreatic venous NE levels like sympathetic nerve stimulation. The medium dose of 120 ng/min (n = 6) reproduced the nerve stimulation-induced decrease of pancreatic blood flow. The high dose of 1,200 ng/min (n = 6) markedly exceeded both. It was found that neither the low nor the medium infusion rates of NE significantly affected pancreatic SLI or PP output. In contrast, infusion of NE at the very high dose level of 1,200 ng/min decreased pancreatic SLI output from 850 +/- 165 fmol/min to 318 +/- 59 fmol/min after 5 min of infusion (delta = -532 +/- 143 fmol/min, P less than 0.01) and decreased PP secretion from 22,777 +/- 7,082 pg/min to 12,764 +/- 6,100 pg/min after 3 min of infusion (delta = -10,013 +/- 2,399 pg/min, P less than 0.01). During this high dose rate NE infusion, both the increment of pancreatic venous SPV levels of NE and the decrement of pancreatic blood flow markedly exceeded the effects produced by sympathetic nerve stimulation. We conclude from this study in dogs: that selective electrical stimulation of the sympathetic nerves entering the pancreas decreases blood flow and inhibits pancreatic SLI and PP secretion, that NE infused into the pancreatic artery at moderate rates reproduces the decrease in blood flow yet does not reproduce the inhibition of pancreatic SLI and PP secretion, and that extremely high concentrations of NE, which markedly restrict pancreatic blood flow, decrease both pancreatic SLI and PP outputs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2885176 TI - The neuropeptide-synthesizing rat 44-2C cell line: regulation of peptide synthesis, secretion, 3,'5'-cyclic adenosine monophosphate efflux, and adenylate cyclase activation. AB - We established in culture a clonal strain (44-2C) which produces calcitonin (CT), CT gene-related peptide, neurotensin (NT), and somatostatin (SS). A compendium of experimental data detailing for this strain the differential regulation of NT, CT, and SS synthesis and secretion, adenylate cyclase activation, and cAMP efflux is presented herein. The effects of hypophysiotropic peptides, brain-gut peptides, and catecholamines are described in detail. The effects of steroid hormones, and in particular, that of the synthetic glucocorticoid, dexamethasone, are presented. The effect(s) of basic bovine fibroblast growth factor are also described. In 44-2C cells basic fibroblast growth factor selectively regulates the synthesis and secretion of CT, NT, SS, and cAMP. Moreover, basic fibroblast growth factor enhances the responsiveness of 44-2C cells to neurosecretory peptides such as rat hypothalamic GRF. We conclude that the 44-2C cells are a useful in vitro tool to study the cellular mechanism(s) controlling the differential synthesis and secretion of neuropeptides. PMID- 2885177 TI - Evidence for a synergistic effect of somatostatin on vasoactive intestinal polypeptide-induced prolactin release in the rat: comparison with its effect on thyrotropin (TSH)-releasing hormone-stimulated TSH release. AB - The present experiments were carried out to clarify the role of endogenous somatostatin (SRIF) in the regulation of PRL and TSH release. The effects of electrical stimulation of the hypothalamic periventricular nucleus (PE) on vasoactive intestinal polypeptide (VIP)-induced PRL and TRH-stimulated TSH secretion were studied using pentobarbital-anesthetized male rats bearing indwelling cannulae in the right atria. The animals were implanted in the PE with bipolar concentric stimulating electrodes 1 week before the experiments began. The effects of a bolus injection or a continuous infusion of SRIF-14 (iv, 7.6 or 10 nmol/100 g BW, respectively) on the PRL or TSH release induced by VIP or TRH were also examined. Electrical stimulation of the PE significantly enhanced VIP induced PRL release 19 min after the bolus injection of VIP (from 29.3 +/- 7.2 to 59.7 +/- 14.9 ng/ml, P less than 0.05). A bolus injection of SRIF had a similar effect and increased the PRL response to VIP (from 29.3 +/- 7.2 to 114.7 +/- 22.4 ng/ml, P less than 0.01). Continuous infusion of SRIF did not decrease the stimulatory effect of VIP on PRL release; on the contrary it significantly increased the PRL response to a first VIP injection (10 min after the onset of SRIF-14 infusion) over that observed after a second administration of VIP. Neither electrical stimulation of the PE nor the bolus SRIF-14 injection modified basal PRL secretion. Electrical stimulation of the PE slightly but significantly increased the TSH response to a bolus injection of TRH, but had no effect on the basal TSH release. In contrast, both the bolus injection and the continuous infusion of SRIF-14 significantly and persistently inhibited the TRH-stimulated TSH release. These results suggest that 1) SRIF does not inhibit VIP-induced PRL secretion in vivo but rather enhances it through some unknown mechanism; 2) SRIF inhibits TRH-stimulated TSH secretion. PMID- 2885178 TI - Effects of aging on cholesterol content and cholesterol-metabolizing enzymes in the rat adrenal gland. AB - Previous studies from this laboratory have documented a progressive decline in basal and ACTH-stimulated corticosterone production in isolated adrenocortical cells as rats age. In the current study we examined the possibility that the aging process exerts this effect by interfering with the mechanism(s) by which cholesterol is processed and/or synthesized by the adrenal gland. Freshly excised adrenals from 2-, 5-, 12-, and 18-month-old rats were used for the measurement of cholesteryl ester, free cholesterol, cholesteryl esterases, and acyl co-enzyme A (CoA)-cholesterol acyltransferase activities as well as key enzymes involved in cholesterol biosynthesis. The results showed that cholesteryl ester content increased in a linear manner with advancing age, while neutral cholesteryl esterase activity decreased steadily until at 18 months of age it reached 40% that of 2-month-old control rats. In contrast, lysosomal acid cholesteryl esterase did not change with age, and acyl CoA: Cholesterol acyltransferase showed only a 33% decrease at 12 months of age. The activity of 3-hydroxy-3 methylglutaryl CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, decreased steadily with advancing age, and at 18 months of age, activity was only half of that in 2-month-old control rats. In contrast, the activities of other enzymes involved in the de novo synthesis of cholesterol, namely acetoacetyl CoA thiolase and HMG CoA synthase, were similar in 2- and 12 month-old rats, while mevalonate kinase activity was significantly lower in the 12-month-old rats. After depletion of plasma lipoprotein cholesterol by 4 aminopyrazolo-[3,4-d]pyrimidine, the intraadrenal cholesteryl ester content in young and aged animals fell significantly. Furthermore, such treatment enhanced the activities of all of the cholesterol de novo synthetic enzymes examined. In addition, HMG CoA synthase and HMG CoA reductase activities rose to much greater levels in both young and old rats compared to acetoacetyl CoA thiolase and mevalonate kinase. Finally, markedly higher activities of HMG CoA reductase were observed in 12- and 18-month-old rats after 4-aminopyrazolo-[3,4-d]pyrimidine treatment. Similar results were seen using 17 alpha-ethinyl estradiol to deplete cholesterol and adrenal sterol ester stores. The metabolism of endogenous cholesterol and exogenous hydroxysterols (which bypass the cAMP-dependent transport of endogenous cholesterol to mitochondrial side-chain cleavage enzyme complex) to corticosterone by collagenase-dispersed adrenocortical cells isolated from rats of various ages were also studied.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2885179 TI - Reduced preprosomatostatin messenger ribonucleic acid in the periventricular nucleus of hypophysectomized rats determined by quantitative in situ hybridization. AB - Physiological evidence suggests that somatostatin (SS) inhibits the release of GH and TSH from the anterior pituitary and that elements of these two systems may feed back to regulate hypothalamic SS release or synthesis. Hypophysectomy reduces hypothalamic SS content in rats, an effect that may be attributable to a change in SS synthesis, storage, or release. We tested the hypothesis that hypophysectomy would reduce hypothalamic SS synthetic capacity, as reflected by a reduction in SS mRNA levels. Using in situ hybridization and a computerized image analysis system, we measured SS mRNA signal levels over individual cells in the periventricular nucleus of hypophysectomized and intact male rats. SS mRNA signal levels were 45.1% lower in hypophysectomized rats compared to those in intact controls (P less than 0.05). These results demonstrate that SS synthetic capacity in the periventricular nucleus is influenced by the presence of the pituitary, and this system may represent one example of the regulation of central nervous system neuropeptide gene expression by a circulating pituitary hormone. PMID- 2885180 TI - Transglutaminase activity in bovine calf testicular membranes: evidence for a possible role in the interaction of follicle-stimulating hormone with its receptor. AB - Transglutaminase (TGase) activity, determined by incorporation of [1,4 14C]putrescine into casein, was demonstrated in a light membrane fraction derived from bovine calf testicular homogenates. In common with other TGases thus far identified, testicular TGase is calcium dependent. A concentration-dependent relationship was observed between decreasing TGase activity and increasing concentrations of N-ethylmaleimide and bacitracin, inhibitors of TGase, and the TGase substrate monodansylcadaverine. Although NEM at all concentrations tested had no effect on [125I]human (h) FSH-receptor binding, dissociation of [125I]hFSH from its receptor was enhanced when [125I]hFSH-receptor complexes were formed in the presence of NEM. Dissociation of [125I]hFSH from its receptor also increased in the presence of bacitracin or monodansylcadaverine. Reduced TGase activity always paralleled increases in hormone-receptor dissociation. The inverse relationship between TGase activity and [125I]hFSH-receptor dissociation observed in this study suggests that TGase activity may be involved in the interaction of FSH with its receptor and that protein cross-linking (via peptide bond formation) may be a mechanism whereby some FSH-receptor complexes are stabilized in the bovine testis. PMID- 2885181 TI - Structural characterization of the somatostatin receptor in rat anterior pituitary membranes. AB - To structurally characterize the somatostatin receptor in the anterior pituitary, the chemical cross-linking reagent N-5-azido-nitrobenzoyloxysuccinimide was used to attach covalently [125I-Tyr11]somatostatin-14 to its receptor in pituitary membranes. Rat anterior pituitary membranes were incubated with [125I Tyr11]somatostatin-14, washed, and then treated with 100 microM cross-linker, which was activated by exposure to UV light. Gel electrophoresis followed by autoradiography revealed a broad band centered at 88,000 mol wt. The appearance of this band was unaffected by dithiothreitol. Competitive inhibition of binding by unlabeled somatostatin resulted in a parallel inhibition of labeling of the 88,000 mol wt protein. The addition of guanine nucleotides in concentrations that inhibit binding similarly inhibited cross-linking. The cross-linked membranes were solubilized in Zwittergent 3-12, a nondenaturing detergent, and the glycosylation pattern of the labeled protein was investigated by incubation with various lectins coupled to agarose. The cross-linked protein was selectively adsorbed by wheat germ agglutinin, and this interaction was blocked by the addition of N,N',N"-triacetylchitotriose, indicating that the rat anterior pituitary somatostatin receptor is a glycoprotein containing polymeric beta-1-4 linked N-acetylglucosamine groups. The results of this study show that the rat anterior pituitary somatostatin receptor is a glycoprotein of 88,000 mol wt containing no disulfide-linked subunits. PMID- 2885182 TI - Characterization of somatostatin receptors which mediate inhibition of insulin secretion in RINm5F insulinoma cells. AB - Somatostatin (SRIF) is a neuropeptide which inhibits secretion from a variety of target cells including pancreatic beta-cells. In this study we have used the RINm5F rat insulinoma cell line to characterize high affinity receptors for SRIF. The binding of 0.03 nM [125I-Tyr11]SRIF to RINm5F cells reached a plateau level within 4 h at 37 C at which time 80% of the total binding could be displaced by 100 nM unlabeled SRIF. In contrast, 100 nM concentrations of eight structurally unrelated peptides did not inhibit [125I-Tyr11]SRIF binding. Scatchard analysis indicated that RINm5F cells contained a single class of noninteracting binding sites (910 +/- 190 sites per cell) with high affinity for [125I-Tyr11]SRIF [equilibrium dissociation constant (Kd) = 0.04 +/- 0.01 nM]. Competition experiments with SRIF analogs showed that the binding affinity for [I-Tyr11]SRIF (Kd = 0.03 +/- 0.02 nM) was higher than that for either SRIF (0.24 +/- 0.04 nM) or [Tyr11]SRIF (0.27 +/- 0.04 nM) and that reduced SRIF analogs bound poorly (Kd greater than 50 nM). These results demonstrate that RINm5F cells possess specific, high affinity binding sites for SRIF. Insulin release stimulated by 20 mM leucine or 15 mM glyceraldehyde was inhibited as much as 80% by maximal concentrations (100 nM) of SRIF. The IC50 for SRIF inhibition of leucine stimulated insulin secretion was 0.43 +/- 0.15 nM, in good agreement with the apparent Kd for binding. In fact, this close correlation between binding affinity and potency to inhibit insulin release was observed for six SRIF analogs, indicating that the characterized binding sites are the receptors which mediate the biological actions of SRIF in RINm5F cells. PMID- 2885183 TI - Regulation of a thyrotropin-releasing hormone-degrading enzyme in GH3 cells: induction of pyroglutamyl peptidase I by 3,5,3'-triiodothyronine. AB - The effect of exposure of GH3 cells to T3 on the TRH-degrading enzymes pyroglutamyl peptidase I (EC 3.4.19.3) and prolyl endopeptidase (EC 3.4.21.26) was studied. T3 produced a dose-dependent increase in the specific activity of pyroglutamyl peptidase I after 3 days of exposure. The EC50 for T3 was 5 X 10( 10) M. The specific activity of prolyl endopeptidase was unaffected by exposure to T3. The increase in pyroglutamyl peptidase I activity was dependent upon the time of exposure of the cells to this hormone. A maximal effect occurred at 72 h. The stimulation of pyroglutamyl peptidase I by T3 was totally blocked by cycloheximide, indicating that this enzyme is induced in GH3 cells by T3. The effect of T3 on the two TRH-degrading enzymes was also studied in the ACTH secreting cell line AtT20. T3 had no effect on these enzymes in the AtT20 cell, suggesting that the effect of T3 on pyroglutamyl peptidase I may be cell specific. These studies indicate that the induction of pyroglutamyl peptidase I by T3 may contribute to the negative feedback regulation of T3 levels. PMID- 2885184 TI - Antiserum to somatostatin-28 augments growth hormone secretion in the rat. AB - To determine directly whether somatostatin-28 (S-28) physiologically regulates GH secretion, and what its contribution is relative to somatostatin-14 (S-14), we have compared the effects of immunoneutralization with a specific S-28 antibody with those of an anti S-14/S-28 serum on GH secretory dynamics in the rat. Plasma samples were obtained every 15 min for 7 h (1000-1700 h) from conscious, chronically cannulated rats after iv administration of 1 ml of one of the following sera: 1) rabbit anti S-28 (reacts with S-28, but not with S-14; maximum binding, 297 pmol/ml), 2) nonimmune rabbit serum, 3) sheep anti-S-14/S-28 serum (maximum binding, 9.4 nmol S-14 or S-28/ml), and 4) nonimmune sheep serum. A comparison of the mean integrated plasma GH levels during peak and trough periods showed significantly higher trough GH levels in both antibody-treated groups compared to those in the corresponding controls. In the anti-S-14/S-28-treated group, the elevation of trough period GH levels (40.5 +/- 3.5 ng/ml) represented a 3.25-fold increase (P less than 0.01) compared to the control value (12.5 +/- 1.5 ng/ml). In the anti-S-28-treated group, trough period GH levels (14 +/- 1.6 ng/ml) showed a 2.3-fold increase (P less than 0.01) compared to the control value (6.1 +/- 0.9 ng/ml). Mean peak period GH levels were 1.35-fold higher (P less than 0.05) than control values in the anti-S-14/S-28-treated group; anti-S 28 serum did not change mean peak GH levels. These data provide strong evidence that circulating S-28 (like S-14) physiologically regulates trough GH secretion and that the contribution of S-28 to GH inhibition is as important as that of S 14. PMID- 2885185 TI - The effect of atracurium, vecuronium and pancuronium on heart rate and arterial pressure in normal individuals. AB - Heart rate and rhythm (from ECG) and systolic, diastolic and mean arterial pressures (using an oscillotonometer) were measured for 30 min following administration of atracurium 0.5 mg kg-1 (n = 20), vecuronium 0.1 mg kg-1 (n = 20) or pancuronium 0.1 mg kg-1 (n = 20) during steady-state anaesthesia, with nitrous oxide, oxygen and either 0.75% halothane or fentanyl 4-5 micrograms kg-1, in the absence of any surgical stimulation. Whereas atracurium and vecuronium were associated with only small and clinically unimportant changes in heart rate, pancuronium produced a marked and significant increase associated with a junctional rhythm in four patients. Atracurium produced no significant changes in arterial pressure, vecuronium produced a significant fall (20 mmHg) in diastolic pressure during halothane anaesthesia and pancuronium a significant increase in mean arterial pressure with both anaesthetic techniques. No serious bradycardias were observed with either atracurium or vecuronium. Five patients showed cutaneous signs of histamine liberation after administration of atracurium. PMID- 2885186 TI - Interactions between atracurium and vecuronium on indirectly elicited muscle twitch in vitro. AB - In vitro experiments using the indirectly stimulated rat phrenic-nerve diaphragm preparation have demonstrated simple summation of the inhibitory actions of vecuronium and atracurium. PMID- 2885188 TI - A new infusion design for atracurium and vecuronium. AB - An infusion technique, designed to reduce the duration of period of no response to nerve stimulation following atracurium (Group I) and vecuronium (Group 2), was studied in 30 patients during neurolept anaesthesia. For intubation a combination of a small bolus injection of the relaxant (ED50) and a continuous infusion were administered. The tactile response to nerve stimulation was used to quantify the degree of relaxation and to adjust the speed of infusion. On the other arm the mechanical twitch was recorded blindly for control. Good to excellent intubation conditions were obtained in 4.3 min with atracurium and in 4.0 min with vecuronium. The total dose given for intubation was 0.36 mg kg-1 atracurium (0.24 0.49 mg kg-1) and 0.064 mg kg-1 vecuronium (0.046-0.084 mg kg-1). The period of no response was zero in seven patients in Group I and in four patients in Group 2. In the remaining patients in Group I the period of no response ranged from 5.0 25.0 min, median 10.9 min, and in Group 2 from 2.5-15.6 min, median 9.5 min. At the time of extubation the train-of-four ratio was 0.71 and 0.72 in Group I and 2, respectively. It is concluded that it is possible to achieve a stable, adjustable, and easily reversible block with this technique, even during surgery of short duration. PMID- 2885187 TI - A comparison of nalbuphine with morphine for post-orchidopexy pain. AB - A double-blind investigation was conducted to compare nalbuphine with morphine for the control of pain after unilateral orchidopexy. Fifty boys under 11 years of age were allocated randomly to receive intramuscular nalbuphine 0.2 mgkg-1 or morphine 0.2 mgkg-1 immediately after induction of anaesthesia. Pain was assessed on a three-point scale, 1, 2 and 4 h after injection and on the morning following operation. Side-effects were also recorded. There were no significant differences between the two drugs in either the provision of analgesia, or the incidence of the principal side-effects of vomiting and sweating. There was a high incidence of vomiting in both groups. Nalbuphine is a satisfactory alternative to morphine for post-orchidopexy pain and may offer the advantages of greater safety and convenience. PMID- 2885189 TI - Post-operative morbidity associated with the use of atracurium and vecuronium in day-case laparoscopy. AB - Patients were randomly allocated to receive either vecuronium or atracurium as the sole muscle relaxant for day-case gynaecological laparoscopy to determine if either agent was superior with respect to post-operative morbidity during the 48 h after operation. Intubating conditions and cardiovascular stability were similar in both groups. Post-operative morbidity prior to discharge was also similar except for a significantly higher incidence of abdominal pain in the vecuronium group. There was no statistical difference in specific morbidity during the 48 h after laparoscopy, but a greater number of patients in the vecuronium group was able to resume normal activity 24 h after laparoscopy. Both agents are very suitable for day-case laparoscopies and other short surgical procedures. PMID- 2885190 TI - Alfentanil infusions: relationship between pharmacokinetics and pharmacodynamics in man. AB - Fourteen fit young patients undergoing body surface surgery received an infusion of alfentanil at either 50 or 100 micrograms kg-1 hr-1 to supplement nitrous oxide anaesthesia. The alfentanil infusion was continued for two hours post operatively at the lower rate of 20 micrograms kg-1 hr-1. Resting ventilation, carbon dioxide responsiveness and pain scores were measured post-operatively. Values for clearance and elimination half life were similar to data following single doses of alfentanil but showed considerable interindividual variation. However, there was a greater systemic clearance (P = 0.02) when determined using the post-infusion decay data compared with that calculated during anaesthesia (527 ml min-1 compared with 434 ml min-1). This is in accord with observations for other intravenous drugs. PMID- 2885191 TI - Recovery of Bordetella pertussis from four kinds of swabs. AB - Calcium alginate, dacron, rayon and cotton wool tipped swabs, in combination with charcoal horse blood transport medium with cephalexin, were compared with regard to their ability to maintain viability of Bordetella pertussis. Calcium alginate proved to be the most suitable swab material. A field trial confirmed the results of the laboratory study. PMID- 2885192 TI - Separation, amino-terminal sequence and cell-free synthesis of the smallest subunit of sweet potato cytochrome c oxidase. AB - The smallest subunit (V) of sweet potato cytochrome c oxidase was separated into three polypeptides, Va, Vb and Vc with different molecular masses (7.4 kDa, 6.8 kDa and 6.2 kDa respectively) by highly resolving sodium dodecylsulfate polyacrylamide gel electrophoresis. Antibody against subunit V reacted specifically with the polypeptide Vc. When polyadenylated mRNA from sweet potato root tissue was translated in a wheat germ cell-free system, the smallest subunit (Vc) of the polypeptides was synthesized to the same size as the mature form, which suggests that the mature subunit retains the signal for import into mitochondria. Within the N-terminal first 25 amino acids there is a stretch of 16 non-polar residues, periodically linked by basic residues, which might form an amphiphilic helix as the targeting signal. PMID- 2885193 TI - Molecular cloning and nucleotide sequence of full-length cDNA for sweet potato catalase mRNA. AB - A nearly full-length cDNA clone for catalase (pCAS01) was obtained through immunological screening of cDNA expression library constructed from size fractionated poly(A)-rich RNA of wounded sweet potato tuberous roots by Escherichia coli expression vector-primed cDNA synthesis. Two additional catalase cDNA clones (pCAS10 and pCAS13), which contained cDNA inserts slightly longer than that of pCAS01 at their 5'-termini, were identified by colony hybridization of another cDNA library. Those three catalase cDNAs contained primary structures not identical, but closely related, to one another based on their restriction enzyme and RNase cleavage mapping analyses, suggesting that microheterogeneity exists in catalase mRNAs. The cDNA insert of pCAS13 carried the entire catalase coding capacity, since the RNA transcribed in vitro from the cDNA under the SP6 phage promoter directed the synthesis of a catalase polypeptide in the wheat germ in vitro translation assay. The nucleotide sequencing of these catalase cDNAs indicated that 1900-base catalase mRNA contained a coding region of 1476 bases. The amino acid sequence of sweet potato catalase deduced from the nucleotide sequence was 35 amino acids shorter than rat liver catalase [Furuta, S., Hayashi, H., Hijikata, M., Miyazawa, S., Osumi, T. & Hashimoto, T. (1986) Proc. Natl Acad. Sci. USA 83, 313-317]. Although these two sequences showed only 38% homology, the sequences around the amino acid residues implicated in catalytic function, heme ligand or heme contact had been well conserved during evolution. PMID- 2885194 TI - Transcription activation of the tyrosine aminotransferase gene by glucocorticoids and cAMP in primary hepatocytes. AB - The expression of the tyrosine aminotransferase (TAT) gene of the rat was analyzed in primary hepatocytes. The TAT gene remains active in primary cultured cells at a level similar to that in liver cells. Expression can be induced by glucocorticoids and cAMP, glucocorticoids lead to a 8-10-fold increase in TAT mRNA level, cAMP to a 20-30-fold increase. The elevation of the TAT mRNA is preceeded by a rise in the relative rate of transcription of the gene. Surprisingly transcription of the albumin gene, which steadily declines with the age of the culture, can also strongly be stimulated by glucocorticoids in primary hepatocytes. cAMP antagonists, which act as competitive inhibitors of the cAMP dependent protein kinase, prevent induction of transcription of the tyrosine aminotransferase gene by cAMP suggesting that the effect of cAMP on expression of the tyrosine aminotransferase gene is mediated by a cAMP-dependent protein kinase. The cAMP antagonist does not interfere with induction by glucocorticoids which suggests that phosphorylation of the glucocorticoid receptor by the cAMP dependent protein kinase is not required for its function. We thus conclude that the two inducers affect transcription by independent mechanisms. PMID- 2885195 TI - Isolation and characterization of coated vesicles from filamentous fungi. AB - Coated vesicles have been shown to exist in Neurospora crassa (Ascomycetes) and Uromyces phaseoli (Basidiomycetes) growing germlings. Separation of coated vesicles in both fungi was obtained when the high-speed (100,000g) pellet was fractioned on a Sephacryl S-1000 gel filtration column, according to the procedure of Mueller and Branton. Electron micrographs of negatively stained coated vesicles from fractions of gel filtration show the same striking lattice coated vesicles similar to vertebrate coated vesicles. We observe two major size classes of coated vesicles in both fungi: the larger class (100-180 nm) is similar in size to vertebrate coated vesicles; the smaller class (50-80 nm) is mostly found in both fungi. When examined by SDS-PAGE, the Sephacryl column fractions containing the maximum concentration of electron microscopically visible coated vesicles coincide with the bands of the protein coat reported as clathrin. The protein composition on SDS-PAGE of the coated vesicles indicates a major polypeptide species of 180 kDa and minor 30 to 36 kDa species. Polypeptides of 100 kDa and 64 kDa are also found in the fractions containing coated vesicles. PMID- 2885196 TI - Modification of the ultrastructure of Entamoeba histolytica after phagocytosis of liposomes loaded with phalloidin. AB - The specific actin-interacting drug phalloidin has been introduced into the cytoplasm of a highly motile amoeba, Entamoeba histolytica, by a new technique: the phagocytosis of liposomes containing phalloidin. After ingestion of these liposomes, two important modifications of the ultrastructure of the amoeba were observed. First, large nodules of densely packed fine filaments are formed, which may be due to the polymerization of actin induced by the release of phalloidin within the cell's cytoplasm. Second, phalloidin induces the proliferation of ribosome crystals known as chromatoid bodies in encysted cells. This formation could be the direct consequence of the action of phalloidin on actin, where filaments form and ribosomes detach from the original oligo or polymers. However, it could also result from an unspecific toxic effect on the amoeba which, under physiological stress, starts to encyst and show multiplication of these chromatoid bodies upon encystment. PMID- 2885198 TI - Lipoprotein-X and diagnosis of biliary atresia. PMID- 2885199 TI - Lipoprotein X, gamma-glutamyltranspeptidase and biliary atresia. PMID- 2885197 TI - Immunomicroscopic localization of aminopeptidase N in the pig enterocyte. Implications for the route of intracellular transport. AB - The subcellular localization of aminopeptidase N (EC 3.4.11.2) in the pig enterocyte was investigated by immunofluorescence and immunoelectron microscopy (immunogold staining). By indirect immunofluorescence on either frozen or paraffin-embedded sections, a very intense staining in the microvillar membrane and a weak intracellular staining was demonstrated. No staining was detected in the basolateral membrane. Likewise, the immunogold labelling on Epon-embedded sections was concentrated in the microvillar membrane, whereas the basolateral membrane did not contain significant amounts of labelling. Labelling was demonstrated in the Golgi apparatus and in a minor fraction of the intracellular smooth vesicles positioned between the Golgi apparatus and the microvillar membrane. These observations are compatible with the view that newly synthesized aminopeptidase N is delivered directly to the microvillar membrane by smooth vesicles having a diameter about 70 to 100 nm and does not pass the basolateral membrane on its way to the brush border membrane. PMID- 2885200 TI - GGT reduction in beta carotene-inhibition of hamster buccal pouch carcinogenesis. AB - Levels of activity for gamma glutamyl transpeptidase (GGT) were studied in hamster buccal pouches developing DMBA-induced epidermoid carcinomas and in pouches in which carcinogenesis was inhibited by topical application of beta carotene. The beta carotene acted to inhibit tumor development when applied topically on days alternate to the application of 0.25% DMBA in heavy mineral oil thrice weekly for 22 weeks. Forty male young adult Syrian hamsters were divided into four equal groups. Group 1 had DMBA applied to left buccal pouches thrice weekly. Group 2 had DMBA applied as in Group 1 but also beta carotene thrice weekly on days alternate to the DMBA application. Group 3 animals were painted with only beta carotene and Group 4 animals were untreated controls. The left buccal pouches were dissected at autopsy and divided in half. One half was fixed in formalin, sectioned in paraffin and stained with hematoxylin-eosin for histologic study. The other half was prepared for the histochemical demonstration of GGT activity using epithelial whole mount preparations. GGT activity was found to be reduced in the left buccal pouches of those animals treated with both beta carotene and DMBA when compared to those animals treated with DMBA alone. PMID- 2885201 TI - Cardiovascular drugs and exercise. PMID- 2885202 TI - Haemodynamic, metabolic, and lymphocyte beta 2-adrenoceptor changes following chronic beta-adrenoceptor antagonism. AB - We have examined the effects of 7 days treatment with beta adrenoceptor antagonists in 8 healthy volunteers in a placebo controlled, crossover study. We investigated three beta-adrenoceptor antagonists (atenolol, oxprenolol, and propranolol), which have differing profiles of selectivity and partial agonist properties (intrinsic sympathomimetic activity, ISA). We studied adrenaline induced hypokalaemia, the vasodilator response to an infusion of adrenaline (0.06 micrograms X kg-1 X min-1 for 90 min), and lymphocyte beta 2-adrenoceptor number, determined by (-) [125I]-iodocyanopindolol binding, and measured these variables both before and after 7 days of treatment. The beta 2-mediated depressor response to adrenaline infusion was abolished by propranolol and oxprenolol but persisted after atenolol. In contrast, the hypokalaemia induced by adrenaline was abolished by all three beta-blockers. Lymphocyte beta 2-adrenoceptor number increased significantly following propranolol treatment, but not after oxprenolol for atenolol. We conclude that up-regulation of lymphocyte beta 2-adrenoceptors is dependent on beta 2-receptor blockade and is modified by ISA. The reversal of the hypokalaemic response by atenolol suggests that beta 1 receptors may contribute to the former effect. Alternatively, since different populations of beta 2 adrenoceptors differ in their susceptibility to antagonists there may also be differences in agonist coupling to beta 2-responses between tissues. PMID- 2885203 TI - The effects of acrivastine (BW825C), diphenhydramine and terfenadine in combination with alcohol on human CNS performance. AB - Two studies were performed to measure the effects of acrivastine (BW825C), an antihistamine, in combination with alcohol on the central nervous system. In one study acrivastine 8 mg, diphenhydramine 50 mg and alcohol 32 ml were administered alone and in combination and compared with placebo. In a second study terfenadine 60 and 120 mg and acrivastine 4 and 8 mg combined with alcohol 32 ml were compared with placebo and alcohol alone. Each study was a double-blind, randomised cross-over design using twelve healthy volunteers. Adaptive tracking, reaction time, body sway, eye movements and subjective effects were measured at intervals after treatments. Acrivastine 8 mg alone did not affect any of these measures in contrast with diphenhydramine. Acrivastine in combination with alcohol caused significantly more impairment of some of the tests than placebo or alcohol alone, but significantly less than diphenhydramine/alcohol, which also affected more tests. In the second study no significant differences were seen between the effects of alcohol alone and combinations of either terfenadine or acrivastine with alcohol. It was concluded that acrivastine 8 mg alone did not impair CNS performance in the tests used. In combination with alcohol significant impairment was seen, but this was less pronounced than after diphenhydramine/alcohol. The second study failed to demonstrate differences between drug/alcohol combinations and alcohol alone confirming that the effect of acrivastine in combination with alcohol is small. PMID- 2885205 TI - Competitive and stereoselective histamine H1 antagonistic effect of cicletanide in guinea-pig isolated ileum. AB - The histamine H1 antagonistic effects of the racemic form and the enantiomers of cicletanide, a new antihypertensive furopyridine derivative, were investigated in guinea-pig isolated ileum. Both the racemic and the (-) enantiomer behaved as competitive histamine antagonists (pA2 values of 6.8 and 7.2, respectively). The (+) enantiomer was at least 100 times less potent than the (-) enantiomer. The H1 blocking effect of cicletanide is the most potent and is the only stereoselective property so far reported for the drug. PMID- 2885204 TI - Acute administration of methylenedioxymethamphetamine: comparison with the neurochemical effects of its N-desmethyl and N-ethyl analogs. AB - The acute and long-term neurochemical effects of three methylenedioxyamphetamine analogs were examined in the serotonergic system of the rat brain. Methylenedioxymethamphetamine as well as its N-desmethyl and N-ethyl derivatives depleted cortical serotonin (5HT) concentrations to less than 30% of control 3 h after drug administration. All three compounds were also very similar in their effects on [3H]5HT release from superfused rat striatal slices. Increasing the size of the N-alkyl substituent did appear to reduce the potency of the agent for inducing [3H]dopamine release. One week following drug administration cortical 5HT concentrations had returned to control levels in animals treated with the N ethyl derivative while the other two analogs produced persistent depletions in transmitter concentrations. The effects of the latter two drugs were correlated with a significant decrease in whole brain synaptosomal [3H]5HT uptake indicating serotonergic nerve terminal damage. N-ethyl-methylenedioxyamphetamine had no effect on synaptosomal 5HT uptake at one week. The (+) stereoisomer of methylenedioxyamphetamine was slightly more potent than the (-) enantiomer at producing the long-term 5HT depletion as previously shown for its N-methyl derivative suggesting similar mechanisms may be responsible for their neurotoxic effects. PMID- 2885206 TI - The major histocompatibility complex and diabetes mellitus. AB - Recent studies have greatly increased the knowledge of the genetics of diabetes mellitus. At present several markers of the disease are under discussion. For insulin-dependent diabetes mellitus there is an association between markers of the histocompatibility complex and the incidence of the disease. The genes of the human histocompatibility complex code for at least three different classes of polymorphic proteins involved in the immune response. Two of them, the class I and the class II antigens are described in the article. The class II antigens are primarily expressed on special cells of the immune system. A typical feature of these antigens is their extensive polymorphism, which is the result of their genetic organization. The occurrence of insulin-dependent diabetes mellitus is more or less strongly associated with the class II antigen types DR3 and/or DR4. Using recombinant DNA technology it is possible to further characterize these and other class II specificities at genetic level. There are data on the occurrence of some class II antigen related DNA restriction fragments. They are much more strongly associated with the susceptibility to the disease than other markers found so far. PMID- 2885207 TI - Regulation of biosynthesis, release and degradation of insulin in cultured rat islets. AB - In order to study the long-term influence of glucose on islet cell functions, biosynthesis of (pro)insulin (3H-leucine incorporation during 3h-incubation both at 50 and 300 mg/dl of glucose), release of insulin and somatostatin and degradation of intra-insular insulin were measured in isolated rat islets, cultured for 3 days at 50, 150 and 300 mg/dl glucose. After culture at 50 mg/dl of glucose, (pro) insulin biosynthesis was very low during 3 h incubation in presence of either 50 or 300 mg/dl glucose; whereas, after culture at 300 mg/dl glucose, a sustained high rate of biosynthesis was observed. This priming-effect concerning hormone release during incubation period, in relation to the previous glucose concentration of culture medium was better proportional for D-cells than for the B-cells. During the 3 days of culture, the percentual differences in hormone release at 50, 150 and 300 mg/dl of glucose were, altogether, also higher for somatostatin than for insulin. Insulin degradation was strongly enhanced during culture at 50 mg/dl glucose (total insulin before culture: 526 +/- 57 microU/islet; after culture at 50, 150 and 300 mg/dl glucose (in islets plus media): 253 +/- 25, 975 +/- 90 and 1030 +/- 96 microU/islet, respectively). The glucose-priming of islet cells differed for the various cell functions. At low glucose concentration the pre-synthesized insulin (which was not needed then physiologically) was again degraded within the islet cells; at higher concentrations of glucose, increased stimulation of the B-cells seemed to be modified by the--paracrine--action of somatostatin. PMID- 2885208 TI - The effects of calcitonin, somatostatin and hypercalcaemia on metabolic and hormonal indicators during an oral glucose tolerance test (OGTT). AB - The authors compared the effect of synthetic salmon calcitonin and synthetic somatostatin (SRIF) and hypercalcaemia on an oral glucose tolerance test (OGTT) in healthy subjects in relation to changes of insulin (IRI), somatotrophin (HGH) and cortisol levels. Calcitonin--100 U--in an intravenous infusion in the course of OGTT markedly altered the pattern of the blood sugar curve and of IRI levels. After the initial retardation of the rise of the blood sugar and IRI levels during the 15th and 30th min, the values of both variables increased parallel during the 120th and 180th min, as compared with the control examination after saline. SRIF--500 micrograms--administered in an intravenous infusion altered the pattern of the blood sugar and IRI curves in a similar way as calcitonin, however during the 120th and 180th minute when the blood sugar levels rose significantly the IRI levels did not rise. The curve of HGH levels on infusion with calcitonin displayed a typical three-phase course, as during the control OGTT. During infusion of SRIF the HGH levels were insignificantly but constantly reduced during the first 60 mins. of the OGTT and thus the typical three-phase shape of the curve was impaired. Calcitonin significantly raised the cortisol levels throughout the OGTT, while SRIF caused their slight decline during the 120th min. Hypercalcaemia induced by infusion of 13.3 mg Ca/kg body weight did not alter significantly the blood levels of glucose, IRI and HGH, but caused a significant rise of the cortisol level throughout the OGTT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885209 TI - The effects of beta-adrenergic blockade on the hypothalamic and neurohypophysial vasopressin and oxytocin content in pinealectomized male rats. AB - Pinealectomized (PX), sham-operated and non operated control rats were injected intraperitoneally (i.p.), once daily at 8.00 over five days, with: (a) 0.9% sodium chloride, (b) propranolol hydrochloride in a dose of 10 mg/kg (= 0.1 ml solution per 100 g b.w.). Three hours following the last injection the animals were decapitated and the content of vasopressin and oxytocin was bioassayed in the hypothalamus and neurointermediate lobe. PX was followed by known decrease of both vasopressin and oxytocin in the hypothalamus and neurohypophysis. In rats not-PX propranolol did not change the vasopressin and oxytocin content in the hypothalamus and neurointermediate lobe. In PX-rats, treatment with propranolol resulted in a distinct increase of the vasopressin in the neurohypophysis. It may be therefore supposed that the beta-adrenergic transmission is in some way involved in the regulatory mechanisms of pineal-neurohypophysial functional relationship. PMID- 2885210 TI - Characterization of adenylate cyclase in human retinal pigment epithelial cells in vitro. AB - Human retinal pigment epithelial cells in culture demonstrate adenylate cyclase activity. It is membrane-bound and modulated by GTP regulatory proteins. It is effectively activated only by beta-adrenergic agonists (L-isoproterenol greater than or equal to L-epinephrine greater than L-norepinephrine) and some prostaglandins (PGE1 and PGE2, but not PGF1 alpha). The adrenergic response appears to be mediated by beta-2 receptors. No inhibitory ligands could be demonstrated. Its characteristics, which are similar to functional adenylate cyclase complexes in other mammalian cells, and its selective and sensitive agonist responsiveness, suggest a possible physiologic role in the regulation of human retinal pigment epithelial-cell function. PMID- 2885211 TI - Opioid peptides inhibit the release of noradrenaline from slices of rat medial preoptic area. AB - Previous circumstantial evidence suggested that endogenous opioid peptides inhibit an excitatory noradrenergic projection to the medial preoptic area (MPOA), and thereby suppress the activity of neurones containing luteinising hormone-releasing hormone and thus systemic concentrations of luteinising hormone (LH) itself. In this paper, we report that electrically stimulated release of 3H Noradrenaline (3H-NA) from perifused slices of rat MPOA is diminished when opioid agonists are added to the incubation medium. Thus, morphine (10 microM), beta Endorphin (1 microM) and met-Enkephalin (1 microM), but not Dynorphin A (1-8) (1 microM), caused a significant decrease in electrically stimulated 3H-NA release. The inhibition was reversed by addition of naloxone (10 microM) to the perifusion medium but 3H-NA release was unaffected by dopamine or acetylcholine (or their antagonists sulpiride and atropine, respectively), or serotonin, neurotensin, muscimol or bicuculline (the latter two being agonist and antagonist respectively for the GABA A receptor). Therefore, the experiments provide direct evidence that brain opioids modulate the noradrenergic input to MPOA neurones and support the hypothesis that this may be one mechanism for the regulation of LH secretion. PMID- 2885213 TI - Somatostatin immunoneutralization overcomes the inhibitory effects of quipazine and pargyline on growth hormone secretion in domestic fowl. AB - The inhibitory effects of pargyline and quipazine on chicken growth hormone secretion were overcome by passive immunoneutralization of endogenous somatostatin (SRIF)-14 or SRIF-28(1-14)-like immunoreactivity. Administration of the specific antisera to control birds pretreated with 0.9% NaCl elevated the basal plasma GH concentrations. These results suggest that peptides with SRIF-14 or SRIF-28(1-14)-like immunoreactivity tonically inhibit GH secretion and are at least partially responsible for the inhibitory effects of pargyline and quipazine on GH release in immature domestic fowl. PMID- 2885212 TI - Postsynaptic long-term potentiation follows coupling of dendritic glutamate application and synaptic activation. AB - Dendritic depolarization, which seems to be involved in the induction of long term potentiation (LTP), was elicited by localized glutamate application. When paired to low frequency synaptic activation in the same area, the subsequent changes had features in common with LTP, expressed as an increased probability of firing and shorter spike latency. The EPSP was not significantly increased. PMID- 2885214 TI - 2,3-Dihydrolinderazulene, a new bioactive azulene pigment from the gorgonian Acalycigorgia sp. AB - A new azulene pigment, 2,3-dihydrolinderazulene, has been isolated along with guaiazulene and linderazulene as bioactive metabolites from the gorgonian Acalycigorgia sp. PMID- 2885216 TI - The isolation of human T-cell leukemia lymphoma virus I. PMID- 2885217 TI - Ca-dependent-chloride and potassium currents in rat Leydig cells. AB - Voltage-clamped membrane currents have been investigated from whole-cell patch clamp recordings performed on single Leydig cells isolated from the adult rat testis. Two outward membrane currents were evoked by depolarizing voltage steps. A potassium current was recorded in cells dialyzed with low (10(-9)-10(-8) M) calcium media. This current was decreased by TEA (10 mM). A chloride current was recorded in cells dialyzed with high (10(-7)-10(-6) M) calcium media. This current was decreased by an external exposure to glutamate. Comparison of the currents at low and high internal calcium concentrations suggests that an increase of the intracellular calcium activates a chloride current. PMID- 2885218 TI - Effect of adrenergic agonists on phosphoinositide breakdown in rat skeletal muscle preparations. AB - Adrenergic regulation of phosphoinositide breakdown in rat skeletal muscle was investigated in 30-min incubations with 10 mM LiCl. In rat hemidiaphragms, prelabelled with D-myo-[2-3H]inositol, addition of alpha-agonists (epinephrine, norepinephrine, phenylephrine) induced a 5-8-fold increase of [3H]inositol monophosphate accumulation. This could be prevented by inclusion of alpha antagonists (phentolamine, prazosin). beta-Agonists and/or beta-antagonists had no effect. Similar experiments with isolated flexor digitorum brevis muscle fibers yielded confirmatory results. Functional integrity of beta-receptor mediated processes was suggested by the beta-agonist-induced increase of glucose 6-phosphate in hemidiaphragms and cAMP in fiber preparations. The results indicate that phosphoinositide breakdown in differentiated rat skeletal muscle is, at least in part, under alpha-adrenergic control. PMID- 2885219 TI - Heterogeneity in the structural basis of the human complement C4A null allele (C4A Q0) as revealed by HindIII restriction fragment length polymorphism analysis. AB - The highly polymorphic fourth component of human complement (C4) is usually encoded by two genes. C4A and C4B, adjacent to the 21-hydroxylase (21-OH) genes, 21-OHA and 21-OHB, and is also remarkable in the high frequency of the 'null' alleles, C4A Q0 and C4B Q0. The molecular basis for the C4A Q0 allele was studied in 26 families through restriction fragment length polymorphism (RFLP) analysis with C4 and 21-OH cDNA probes after digestion of the DNA with the endonuclease HindIII. The individuals expressing the extended haplotype HLA-A1 (of A2) Cw7 B8 C2C BfS C4AQ0B1 DR3 have a large deletion taking off the C4A and 21-OHA genes. PMID- 2885221 TI - Differential expression of an alpha-tubulin gene during the development of Physarum polycephalum. AB - The expression of an alpha-tubulin gene (altB1 (N alpha Tu) [(1987) J. Mol. Biol. 193, 427-438]) of Physarum polycephalum (strain CLdAXE) was found to be governed by a developmental switch since mRNA transcripts were detected, by S1 nuclease analysis, in the plasmodial but not the amoebal phase of the life-cycle. The conclusion that the altB1 (N alpha Tu) allele codes for a plasmodial specific alpha-tubulin isotype is supported by recent amino acid sequence data. PMID- 2885215 TI - Coexistence of peptides with classical neurotransmitters. AB - In the present article the fact is emphasized that neuropeptides often are located in the same neurons as classical transmitters such as acetylcholine, 5 hydroxy-tryptamine, catecholamines, gamma-aminobutyric acid (GABA) etc. This raises the possibility that neurons produce, store and release more than one messenger molecule. The exact functional role of such coexisting peptides is often difficult to evaluate, especially in the central nervous system. In the periphery some studies indicate apparently meaningful interactions of different types with the classical transmitter, but other types of actions including trophic effects have been observed. More recently it has been shown that some neurons contain more than one classical transmitter, e.g. 5-HT plus GABA, further underlining the view that transfer of information across synapses may be more complex than perhaps hitherto assumed. PMID- 2885220 TI - Bacterial lectins, cell-cell recognition and infectious disease. AB - Numerous bacterial strains produce surface lectins, commonly in the form of fimbriae that are filamentous assemblies of protein subunits. Among the best characterized of these are the type 1 (mannose specific) fimbrial lectins of Escherichia coli that consist almost exclusively of one class of subunit with a molecular mass of 17 kDa. They possess an extended combining site corresponding to a trisaccharide and preferentially bind carbohydrate units of oligomannose or hybrid type. Type 1 fimbriae also possess a hydrophobic region close to the carbohydrate-binding site, since aromatic alpha-mannosides inhibit strongly (up to 1000-times more than methyl alpha-mannoside) the agglutination of yeasts by the bacteria and the adherence of the latter to pig ileal epithelial cells. The combining sites of type 1 fimbriae of the salmonellae and of other enteric bacteria are different from those of E. coli in that they are smaller and do not possess a hydrophobic region. The various bacterial surface lectins appear to function primarily in the initiation of infection by mediating bacterial adherence to epithelial cells, e.g. in the urinary and gastrointestinal tracts. The mannose specific lectins also act as recognition molecules in lectinophagocytosis (i.e. phagocytosis of the bacteria in the absence of opsonins) by mouse, rat and human peritoneal macrophages, and human polymorphonuclear leukocytes. Affinity chromatography of membrane lysates from human polymorphonuclear leukocytes on immobilized type 1 fimbrial lectin, using methyl alpha-mannoside as eluent, showed that glycoproteins with apparent molecular masses of 70-80, 100 and 150 kDa act as receptors for the bacteria. Inhibition experiments with monoclonal antibodies suggest that the glycoprotein bands of 100 and 150 kDa may be identical with the alpha and beta subunits of leukocyte complement receptors and adhesion glycoproteins involved in complement mediated opsonophagocytosis. The systems described serve as a fine illustration for the biological role of lectin-carbohydrate interactions. Further studies of these systems will lead to a deeper understanding of the molecular basis of infectious diseases, and perhaps also to new approaches for their prevention. PMID- 2885222 TI - The amino acid sequence of toxin RpIII from the sea anemone, Radianthus paumotensis. AB - The amino acid sequence of the sodium channel toxin RpIII from the sea anemone Radianthus paumotensis has been determined. The protein is homologous with five analogous toxins from three anemone species, and is most similar to a less toxic protein, RpII, from the same organism. Twelve residues are conserved in all six toxins, one of which is an arginine residue thought to be essential for toxicity. The others (Cys, Gly, Pro and Trp) tend to be conserved in other sets of homologous proteins to maintain functional folds. Comparisons of the sequences suggest the existence of two separate but related classes of toxins cumon the three species of anemone. PMID- 2885223 TI - Alpha 2-adrenergic inhibition of pancreatic islet glucose utilization is mediated by an inhibitory guanine nucleotide regulatory protein. AB - The rate of glucose utilization in isolated pancreatic islets of the rat was inhibited by the alpha 2-adrenoceptor agonists clonidine and epinephrine. Yohimbine reversed the inhibition. alpha 1 or beta-adrenoceptor agonists had little or no effect on glucose utilization. Stimulation of muscarinic receptors by carbamylcholine reversed the effect of clonidine. Pertussis toxin blocked the effect of clonidine on glucose utilization, and potentiated the response to carbamylcholine. 8-Bromo-cAMP did not affect glucose utilization in the presence of clonidine. Thus, alpha 2-adrenoceptors negatively modulate glucose utilization, and the effect is mediated by an inhibitory guanine nucleotide regulatory protein, but not by cAMP. PMID- 2885224 TI - Somatostatin inhibits VIP- and isoproterenol-stimulated cyclic AMP accumulation in rat prostatic epithelial cells. AB - The dual regulation of cyclic AMP accumulation was studied in rat prostatic epithelial cells incubated with somatostatin, vasoactive intestinal peptide (VIP), and the beta-adrenergic agent isoproterenol. Somatostatin noncompetitively inhibited the stimulatory effect of VIP and isoproterenol, but it did not alter basal cyclic AMP levels. In addition to the multifactorial regulation of the cyclic AMP system in rat prostatic epithelium, these results suggest that somatostatin may play a physiological role at this level. PMID- 2885226 TI - Beta-subunit of Escherichia coli F1-ATPase. An amino acid replacement within a conserved sequence (G-X-X-X-X-G-K-T/S) of nucleotide-binding proteins. AB - A mutant strain KF87 of E. coli with a defective beta-subunit (Ala-151----Val) of F1-ATPase was isolated. The mutation is within the conserved sequence (G-X-X-X-X G-K-T/S) of nucleotide-binding proteins. The mutant F1-ATPase had a much higher rate of uni-site hydrolysis of ATP than the wild type, and about 6% of the wild type multi-site activity. The mutant enzyme showed defective transmission of conformational change(s) between the ligand- and aurovertin-binding sites. PMID- 2885225 TI - Activation of polyphosphoinositide phospholipase C by guanosine 5'-O-(3 thio)triphosphate and fluoroaluminate in membranes prepared from a human T cell leukemia line, JURKAT. AB - Polyphosphoinositide hydrolysis was studied in membranes prepared from a human T cell leukemia line, JURKAT, prelabeled with myo-[2-3H]inositol. The formation of inositol bis- and trisphosphates was stimulated in a buffer with 110 nM free Ca2+ with a nonhydrolyzable GTP analogue, GTP gamma S, and NaF plus AlCl3 in a time- and concentration-dependent manner. GTP gamma S and NaF-AlCl3 had no significant effect on the inositol monophosphate level. AlCl3 enhanced the NaF-stimulated release of inositol polyphosphates. Optimum concentrations of NaF and AlCl3 produced 1.5-fold more inositol polyphosphates than that produced by optimum concentration of GTP gamma S. OKT3 monoclonal antibody, an antibody against the T cell receptor complex, did not stimulate the inositol polyphosphate formation by JURKAT membranes even in the presence of GTP, although the antibody at the concentrations used markedly stimulated the hydrolysis of polyphosphoinositides in intact JURKAT cells. PMID- 2885228 TI - Characterization of the nucleotide tight-binding sites of the isolated mitochondrial F1-ATPase. AB - The properties of the nucleotides tightly bound with mitochondrial F1-ATPase were examined. One of three bound nucleotide molecules is localized at the site with Kd approximately 10(-7) M and released with koff approximately 0.1 s-1. The second nucleotide molecule is bound with the enzyme with Kd approximately 10(-8) M and koff for its dissociation is 3 X 10(-4) s-1. The third is never released even in the presence of 1 mM ATP or ADP. The last two nucleotides are believed to be bound at the noncatalytic sites of F1-ATPase. Pyrophosphate promotes liberation of two releasable nucleotide molecules, decreasing the affinity of the enzyme to AD(T)P. From the results obtained it follows that the only suitable criterion for localization of the nucleotide at the F1-ATPase catalytic site is the high rate (koff greater than or equal to 0.1 s-1) of its spontaneous release. PMID- 2885227 TI - Pseudo arylsulfatase A deficiency. Biosynthesis of an abnormal arylsulfatase A. AB - Pseudo arylsulfatase A deficiency, an asymptomatic condition, and metachromatic leukodystrophy, a severe neurodegenerative disease, are both associated with profound reductions of arylsulfatase A activity in man. We now report that with metabolic labelling, cultured pseudo deficient cells synthesized about 20% of the normal amount of arylsulfatase A at a reduced rate of apparent synthesis and increased rate of degradation. However, in the presence of ammonium chloride which stimulated secretion of lysosomal enzymes, these cells synthesized about 80% of the normal amount of enzyme protein. Hence, the defect in pseudo arylsulfatase A deficiency is associated with labile arylsulfatase A molecules which can be stabilized if they are diverted from intracellular storage. PMID- 2885229 TI - Brain 14-3-3 protein is an activator protein that activates tryptophan 5 monooxygenase and tyrosine 3-monooxygenase in the presence of Ca2+,calmodulin dependent protein kinase II. AB - We have found that the 14-3-3 protein, an acidic neuronal protein, is substantially identical to the 'activator' protein [(1981) J. Biol. Chem. 256, 5404-5409] that activates tryptophan 5-monooxygenase and tyrosine 3-monooxygenase in the presence of Ca2+, calmodulin dependent protein kinase II. This finding is based on the remarkable similarity of both these proteins in physicochemical, biochemical and immunochemical properties, as well as on detection for the 14-3-3 protein of an activator activity towards tryptophan 5-monooxygenase. The result suggests that the 14-3-3 protein plays a role in the regulation of serotonin and noradrenaline biosynthesis in brain. PMID- 2885230 TI - Tumours of the diffuse endocrine system. PMID- 2885232 TI - Transverse testicular ectopia: a case report. PMID- 2885233 TI - [Plasma welding. An alternative to traditional solder in the dental technical laboratory]. PMID- 2885231 TI - The effect of feeding aflatoxin-contaminated groundnut meal, with or without ammoniation, on the development of gamma-glutamyl transferase positive lesions in the livers of Fischer 344 rats. AB - The detoxification of aflatoxin-containing groundnut meal by ammoniation has been investigated using weanling male and female Fischer 344 rats. Rats were fed a pelleted diet consisting of 75% groundnut meal and 25% powdered rat diet, with vitamin supplement, for a period of 90 days. The groundnut meal was either aflatoxin-free or naturally contaminated with aflatoxins, and was used untreated or after ammoniation. Body weights and food consumptions were monitored throughout the experimental feeding period. After 90 days the animals were sacrificed and the gamma-glutamyl transferase (GGT) levels in the livers assayed fluorimetrically, and the distribution of the enzyme activity determined histochemically. The results indicated that ammoniation of the aflatoxin containing meal eliminated the development of focal GGT positive lesions in both male and female animals. However, in the female, histochemical GGT staining of hepatocytes in the periportal areas was increased by all the experimental diets compared with the unammoniated, aflatoxin-free diet. This observation was supported by the fluorimetric assays. Ammoniation of the diet led to a decreased body weight gain in all cases compared with the corresponding unammoniated diet fed groups. PMID- 2885235 TI - Bioenergetics of tumor cells: glutamine metabolism in tumor cell mitochondria. PMID- 2885234 TI - Thy-1 evolution. PMID- 2885236 TI - Glutamine synthetase gene transcription in cultured 3T3-L1 adipocytes: regulation by dexamethasone, insulin and dibutyryl cyclic AMP. AB - We have investigated the regulation of glutamine synthetase (GS) mRNA synthesis in cultured 3T3-L1 adipocytes. Specific mRNA synthesis (transcription) was analyzed by measuring elongation of transcripts in isolated nuclei. Transcription rate was assayed by hybridization of newly synthesized [32P]RNA to a GS cDNA. GS transcription rate increased more than 100-fold during adipocyte differentiation and was inhibited more than 90% by alpha-amanitin. In 3T3-L1 adipocytes dexamethasone stimulated GS gene transcription while insulin and dibutyryl cAMP decreased GS gene transcription. PMID- 2885237 TI - Sea urchin actin gene linkages determined by genetic segregation. AB - Genetic linkage between the actin genes of Strongylocentrotus purpuratus was investigated by observing the segregation of restriction fragment length polymorphisms (RFLPs). Specific RFLPs of actin gene pairs CyI/CyIIa and CyIIIa/CyIIIb always cosegregated, confirming the linkage groups CyI-CyIIa-CyIIb previously previously determined by molecular cloning. In contrast, RFLPs of actin genes CyI/CyIIa, CyIIIa/CyIIIb, and M all segregated at random with respect to one another. This demonstrates that the known actin gene clusters CyI-CyIIa CyIIb, CyIIIa-CyIIIb, and the M actin gene are not closely linked. PMID- 2885238 TI - Alpha-adrenergic blockade improves glucose-potentiated insulin secretion in non insulin-dependent diabetes mellitus. AB - The impairment of glucose-potentiated insulin secretion present in non-insulin dependent diabetes mellitus (NIDDM) can be approximated in normal subjects by an epinephrine infusion. Therefore, we sought to determine the role of the endogenous sympathetic nervous system in glucose-potentiated insulin secretion in both NIDDM (n = 6) and normal (n = 6) subjects. Glucose-potentiated insulin secretion was calculated as the slope of the curve relating increasing ambient glucose levels to the acute insulin response to an intravenous pulse of 5 g of L arginine. Glucose-potentiated insulin secretion was determined on separate days during alpha-, beta-, and combined alpha- plus beta-adrenergic blockade and compared with a saline control. In normal subjects, there was no effect of alpha , beta-, or alpha- plus beta-blockade on the slope of glucose potentiation. In NIDDM, the initially decreased slope of glucose potentiation (0.25 +/- 0.06 microU X ml-1 X mg-1 X dl, mean +/- SE; P less than .01) was not affected by beta blockade but increased during alpha-blockade (0.91 +/- 0.22 microU X ml-1 X mg-1 X dl; P less than .05). However, this improvement was abolished by combined alpha plus beta-blockade (0.32 +/- 0.07 microU X ml-1 X mg-1 X dl). Plasma norepinephrine was increased above basal levels in both normal (+260 +/- 89 pg/ml) and NIDDM (+438 +/- 162 pg/ml) subjects during alpha-blockade (P less than .05 for both). This increase in plasma norepinephrine strongly suggests that there is an increase in synaptic cleft norepinephrine concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885239 TI - Inhibition of [14C]aminopyrine uptake in rat isolated gastric mucosal cells by two classes of psychotropic agents. AB - Certain CNS-active compounds decrease gastric acid secretion in vivo. In this study a number of tricyclic antipsychotic or antidepressant compounds together with haloperidol, a nontricyclic antipsychotic agent, were shown to inhibit dibutyryl-cAMP-stimulated [14C]aminopyrine uptake, an index of acid secretory activity in a rat isolated gastric mucosal cell preparation. The observed order of potency was: thioridazine greater than chlorpromazine greater than haloperidol approximately equal to desipramine approximately equal to imipramine greater than clozapine. Comparison of these potencies with those of the known (H+ + K+)ATPase inhibitors timoprazole and omeprazole revealed that the potency of timoprazole was similar to the one of clozapine while omeprazole was intermediate between thioridazine and chlorpromazine. Pirenzepine was ineffective. PMID- 2885240 TI - Inhibitory effect of somatostatin on cholera toxin-induced diarrhea and glycoenzyme secretion in rat intestine. AB - The effects of somatostatin on cholera toxin-induced secretory diarrhea and the appearance of glycoenzymes in the intestinal lumen and intestinal lymph were investigated in rat small intestine. After exposure to cholera toxin, marked fluid accumulation in the small intestinal tract and elevation of the jejunal mucosal cyclic AMP (cAMP) concentration were observed. The activity of alkaline phosphatase, aminopeptidase and sucrase increased in the intestinal lumen after toxin exposure. In intestinal lymph, alkaline phosphatase activity was increased after cholera toxin administration, while aminopeptidase activity remained unchanged. Somatostatin suppressed cholera toxin-induced secretory diarrhea, but it did not affect the elevated mucosal cAMP concentration. This peptide also inhibited the appearance of glycoenzymes in the intestinal lumen and lymph induced by cholera toxin administration. These results suggest that somatostatin exerts its inhibitory effects on cholera toxin-induced secretory diarrhea and on the appearance of glycoenzymes in the intestinal lumen and lymph by affecting processes beyond cAMP formation. PMID- 2885241 TI - Distribution of gastrin-releasing peptide (GRP)-like immunoreactivity in the rat. AB - Rat tissues were examined for gastrin-releasing peptide (GRP)-like immunoreactivity, using carboxy-terminus-specific antibody made against GRP (19 27), which is thought to be the biologically active site and to be common among species. The distribution of GRP-like immunoreactivity in the rat was similar to that of bombesin-like immunoreactivity. Sephadex G 50 chromatography revealed two peaks of GRP-like reactivity in the rat stomach. Immunohistochemical studies using the antiserum to GRP (19-27) revealed numerous nerve fibers in the mucosa of the rat stomach. In the antral mucosa, GRP-containing nerves were present mainly around the base of the antral glands. Some GRP-containing nerves were in contact with gastrin-containing cells and somatostatin-containing cells. GRP containing nerve fibers were numerous in the middle portion of the oxyntic gland, where somatostatin-containing cells were also detected. None of the endocrine cells stained positively with anti-GRP serum. These results support the hypothesis that GRP is a neurotransmitter in the stomach and that the peptide plays a physiological role in the gastrointestinal tract. PMID- 2885242 TI - A case of salicylazosulfapyridine (Salazopyrin)-induced acute pancreatitis with positive lymphocyte stimulation test (LST). AB - A case of acute pancreatitis induced by salicylazosulfapyridine (Salazopyrin, SASP) was reported. A 33-year-old man with ulcerative colitis was given SASP. Five weeks later, P-type serum amylase was found to be elevated. The amylase/creatinine clearance ratio (ACCR) and serum lipase were also elevated. There were neither subjective symptoms nor abnormal ultrasound findings in the pancrease. Lymphocyte stimulation test (LST) to SASP was positive. Asymptomatic pancreatitis by SASP was suspected and SASP administration was halted. Afterwards the abnormal data became normal. Readministration of SASP because of relapse caused an episode of pancreatitis similar to the first occasion. LST was negative before SASP intake and became positive after intake. Desensitization to SASP was unsuccessful. LST was negative before attempting desensitization and became positive when the dosage of SASP increased to 100 mg daily. This is the second case of acute pancreatitis reported to be induced by SASP and this is the first case in which LST to SASP was described. To our knowledge, this is also the first case in which a positive LST was described in drug-induced pancreatitis. This case provides evidence for the role of delayed type hypersensitivity in the etiopathogenesis of SASP allergy and of dose-independent drug-induced pancreatitis. PMID- 2885243 TI - Water and sodium transport: effects of calcium channel blocker and calmodulin antagonists on the apical and basolateral membranes of amphibian epithelia. AB - Ca2+ channel blocker (sensit) and calmodulin antagonists (thioridazine, perphenazine, oxyprothepine) applied to the mucosal side of frog urinary bladder, weakened the response of epithelial cells to vasopressin. Thioridazine (2.7 X 10( 5) mol X l-1) and sensit (1.7 X 10(-4) mol X l-1) applied to the serosal side rapidly increased the permeability of the epithelia for sodium and potassium ions along the concentration gradient (from serosa to mucosa). The same concentrations of these blockers when applied to the mucosal side of frog urinary bladder selectively decreased vasopressin stimulated water permeability and did not influence ionic permeability. Both thioridazine and sensit decreased the short circuit current across frog skin. The results show that the Ca2+ channel blocker and the calmodulin antagonists tested influenced water and ionic transport across the epithelial cell membranes, and had different effects upon the apical and the basolateral cell membranes. PMID- 2885244 TI - The action of adrenoceptor agonists and antagonists on the guinea pig and dog trachea. AB - The action of beta- and alpha-adrenoceptor agonists (isoprenaline, orciprenaline, noradrenaline, phenylephrine and ephedrine) and antagonists (propranolol, metipranolol, exaprolol, BL 445 and phentolamine) on the resting tension and cAMP level of the guinea pig and the mechanical and electrical activities of the dog trachea were studied. By activating beta 2-adrenoceptors, isoprenaline and orciprenaline relaxed the smooth muscle, elevated the membrane potential and attenuated the excitatory effect of histamine on membrane potential and muscle tension. Noradrenaline and phenylephrine, acting on alpha 1-receptors, did not affect the membrane potential and increased the basal tension of the dog trachea only insignificantly. Ephedrine, in high concentrations, however, hyperpolarized the smooth muscle membrane and relaxed the dog trachea, while it did not alter the cAMP level in the guinea pig preparations. It is, therefore unlikely that alpha 1-adrenoceptors play a major role in the excitation of the dog trachea under resting conditions whereas the participation of alpha 2-receptors in the mechanisms of adrenergic relaxation could not be ruled out. All the beta adrenoceptor antagonists studied enhanced the action of low isoprenaline concentrations and competitively antagonized it in high concentrations. The order of their antagonistic potency in the guinea pig trachea was as follows: metipranolol greater than propranolol = exaprolol greater than or equal to BL 445. It was suggested that metipranolol and exaprolol are nonselective beta adrenoceptor antagonists, similarly as propranolol, whereas BL 445 shown some beta 1-selectivity. In contrast to their antagonistic effects on the membrane activities and muscle tension, both histamine and isoprenaline increased the level of cAMP in smooth muscle cells and, when present simultaneously, their effect was additive. The mechanism of histamine-induced cAMP level elevation and the possible involvement of different subcellular compartments in the action of isoprenaline and histamine in relation to the contraction-relaxation cycle is discussed. PMID- 2885245 TI - Molecular evolution and nucleotide sequences of the maize plastid genes for the alpha subunit of CF1 (atpA) and the proteolipid subunit of CF0 (atpH). AB - The nucleotide sequences of the maize plastid genes for the alpha subunit of CF1 (atpA) and the proteolipid subunit of CF0 (atpH) are presented. The evolution of these genes among higher plants is characterized by a transition mutation bias of about 2:1 and by rates of synonymous and nonsynonymous substitution which are much lower than similar rates for genes from other sources. This is consistent with the notion that the plastid genome is evolving conservatively in primary sequence. Yet, the mode and tempo of sequence evolution of these and other plastid-encoded coupling factor genes are not the same. In particular, higher rates of nonsynonymous substitution in atpE (the gene for the epsilon subunit of CF1) and higher rates of synonymous substitution in atpH in the dicot vs. monocot lineages of higher plants indicate that these sequences are likely subject to different evolutionary constraints in these two lineages. The 5'- and 3' transcribed flanking regions of atpA and atpH from maize, wheat and tobacco are conserved in size, but contain few putative regulatory elements which are conserved either in their spatial arrangement or sequence complexity. However, these regions likely contain variable numbers of "species-specific" regulatory elements. The present studies thus suggest that the plastid genome is not a passive participant in an evolutionary process governed by a more rapidly changing, readily adaptive, nuclear compartment, but that novel strategies for the coordinate expression of genes in the plastid genome may arise through rapid evolution of the flanking sequences of these genes. PMID- 2885246 TI - Dimorphic markers for the human apolipoprotein CII gene locus. AB - Two restriction-site polymorphisms (RSP) have been detected when using a human apolipoprotein CII (apoCII) cDNA clone as a hybridization probe. These include a BanI and a TaqI RSP. Frequencies of the more common allele have been determined in a German population of 100 individuals and are 0.66 (BanI RSP) and 0.56 (TaqI RSP). Corresponding polymorphic information content (PIC) values are 0.36 and 0.37 for individual sites, and 0.58 for the BanI-TaqI pair of sites, making this locus a very informative (PIC-rich) marker for this region of chromosome 19. Haplotype studies also indicate the presence of allelic association (linkage disequilibrium) at the human apoCII gene locus. PMID- 2885247 TI - Rapid localization and characterization of random mutations within the 2 micron circle site-specific recombinase: a general strategy for analysis of protein function. AB - A method for rapidly localizing and characterizing mutations within the 2 micron circle site-specific recombinase enzyme (FLP) is described. The strategy consists of dividing the gene coding for FLP (FLP) by artificially introduced unique restriction enzyme sites (that do not alter the amino acid sequence of the protein) into segments of 150-200 bp, mutagenizing the engineered gene and selecting mutants in vivo, localizing each mutation to one of the gene segments by an in vivo complementation assay, and characterizing the mutation by sequencing of only this DNA segment. The experimental designs embodied by this method should be of wide application in investigations of protein function in general and of DNA-protein interactions in particular. PMID- 2885248 TI - [Minidose naloxone reverses respiratory depression, but not analgesia, at the end of narcotic-supplemented anesthesia]. PMID- 2885250 TI - [Hypertension therapy today]. PMID- 2885249 TI - [Terfenadine in allergic respiratory tract diseases. General practice study on the effectiveness and tolerance in children]. PMID- 2885251 TI - Amiodarone: a common source of iodine-induced thyrotoxicosis. AB - Amiodarone, a iodine-rich drug widely used in the treatment of tachyarrhythmias, represents one of the most common sources of iodine-induced thyrotoxicosis. The data concerning 58 patients with amiodarone-iodine-induced thyrotoxicosis (AIIT) were analyzed in the present study. Prevalence of AIIT was higher in males than in females (M/F = 1.23/l). Thyrotoxicosis occurred either during treatment with or at various intervals after withdrawal of amiodarone. AIIT developed not only in patients with underlying thyroid disorders, but also in subjects with apparently normal thyroid gland. Classical symptoms of thyrotoxicosis were often lacking, the main clinical feature being a worsening of cardiac disorders. Biochemical diagnosis of AIIT was established by the finding of elevated serum total and free triiodothyronine levels, since elevated serum total and free thyroxine could be found also in euthyroid amiodarone-treated subjects. Twenty four-hour thyroid radioiodine uptake was very low or undetectable in AIIT patients with apparently normal thyroid glands, while it was inappropriately elevated in patients with underlying thyroid disorders, despite iodine contamination. The role of autoimmune phenomena in the pathogenesis of AIIT appeared to be limited, because circulating thyroid autoantibodies were undetectable in AIIT patients without underlying thyroid disorders or with nodular goiter. Conversely, humoral features of thyroid autoimmunity were mostly found in AIIT patients with diffuse goiter. Treatment of AIIT appeared to be a difficult challenge. Among the 11 patients given no treatment, thyrotoxicosis spontaneously subsided in the 5 patients with apparently normal thyroid gland, whereas the 6 patients with nodular or diffuse goiter were still hyperthyroid 6-9 months after discontinuation of the drug. The administration of high doses (40 mg/day) of methimazole alone proved to be ineffective in most (14/16) patients given this treatment. Twenty-seven patients were treated by methimazole combined with potassium perchlorate (1 g/day). With one exception, euthyroidism was restored within 15-90 days in all cases with underlying thyroid abnormalities, and within 6-55 days in subjects with apparently normal thyroid gland. Thus, the combined treatment appears to be the most effective one, but, due to the potential toxicity of potassium perchlorate, it should be reserved to patients with severe thyrotoxicosis and should be carefully monitored. PMID- 2885252 TI - Leu M-1 antigen: comparative expression in Hodgkin's disease and T cell lymphoma. AB - Expression of the granulocyte antigen Leu M-1 is characteristic of Reed-Sternberg cells and the related mononuclear cells of Hodgkin's Disease. Leu M-1 has been proposed as a specific immunological marker for Hodgkin's Disease which may be otherwise difficult to distinguish both morphologically and immunologically from non Hodgkin's lymphomas of peripheral T-cell type. In the present study the comparative expression of Leu M-1 in Hodgkin's Disease and peripheral T cell lymphoma was studied in a series of 43 cases including 25 cases of Hodgkin's Disease and 18 cases of immunologically documented peripheral T cell lymphoma. Leu M-1 staining by avidin-biotin-peroxidase complex technique in acetone fixed frozen sections was observed in 22 of 25 cases of Hodgkin's Diseases, (2 of 3 cases of lymphocyte predominant Hodgkin's Disease and 1 case of mixed cellularity were negative) and in 4 of 18 cases of peripheral T cell lymphoma. The pattern of staining in the peripheral T cell lymphomas was indistinguishable from that observed in Hodgkin's Disease in 2 of the cases. Leu M-1 staining appears to be of limited diagnostic value in the differential diagnosis of Hodgkin's Disease and T cell lymphoma. Absence of Leu M-1 staining in frozen tissue however, makes a diagnosis of Hodgkin's Disease (with the exception of the lymphocyte predominant form) unlikely. PMID- 2885253 TI - Formed visual hallucinations in an elderly patient. PMID- 2885254 TI - Linkage analysis with RFLPs in families with androgen resistance syndromes: evidence for close linkage between the androgen receptor locus and the DXS1 segment. AB - Three families with androgen resistance syndromes--two with testicular feminization and one with Reifenstein syndrome--have been studied for linkage analysis. Using three cloned DNA sequences from the centromere region and the proximal long arm of the X chromosome (p8, pDP34, and S9, which define respectively the chromosomal segments DXS1, DXYS1, and DXS17), we found no recombination between the DXS1 locus and the mutant genes in the three families. Assuming that these disorders are the result of allelic mutations at the same locus for the androgen receptor, we can conclude that there is a close linkage between DXS1 and the androgen receptor locus, with a maximum lod score zeta = 3.5 at a recombination fraction theta = 0.0 using the LIPED program (Ott 1974). PMID- 2885255 TI - RFLP analysis in families with sporadic hemophilia A. Estimate of the mutation ratio in male and female gametes. AB - To investigate the sporadic occurrence of hemophilia A and to estimate the sex ratio of mutation rates directly, 17 families with isolated cases of the disorder were studied by RFLP analysis and by clotting assays. Three RFLPs, one intragenic and two with close linkage to hemophilia A, were used. In eight families the RFLP study excluded the carrier status of the maternal grandmothers. Since hemostatic studies showed that the eight mothers of these propositi were hemophilia carriers, the origin of the newly mutated genes was inferred from the RFLP patterns: six hemophilic genes derived from the normal maternal grandfathers and two, from maternal grandmothers. The data indicate a higher mutation rate in males than in females, as previously suggested by segregation analysis and coagulation studies. However the sex ratio indicated by the RFLP analysis is lower than previously reported and could explain previous conflicting estimates. PMID- 2885256 TI - Detection of submicroscopic deletions and a DNA polymorphism at the retinoblastoma locus. AB - DNA samples from 60 unrelated patients with retinoblastoma were screened by Southern blot hybridization using two probes that are closely linked to the retinoblastoma locus within human chromosome band 13q14. Seven of 44 patients with bilateral or multifocal unilateral retinoblastoma and one patient with unifocal unilateral retinoblastoma were found to have a heterozygous deletion for the anonymous DNA sequence H3-8. Three of the eight deletions did not include the esterase D locus and were undetectable by conventional cytogenetic analysis. The findings are compatible with the deletions being the cause of retinoblastoma in these cases and provide a basis for DNA diagnosis in nearly 20% of patients with bilateral and multifocal unilateral retinoblastoma. The H3-8 probe also detects a restriction fragment length polymorphism that is a useful genetic marker in some families. PMID- 2885257 TI - Rapid RFLP screening procedure identifies new polymorphisms at albumin and alcohol dehydrogenase loci. AB - A rapid screening procedure for restriction fragment length polymorphisms (RFLPs) is reported. DNA from ten individuals is pooled and compared to DNA isolated from a cell line containing a single chromosome 4. This single chromosome-containing line is an obligate hemizygote for chromosome 4 RFLPs so that only one band corresponding to a single allele will appear on a Southern blot. In the pooled DNA sample lane bands corresponding to both alleles will be seen. The technique allows for efficient detection of RFLPs with easier use of large numbers of enzymes. It provides estimates of allele frequencies and disequilibrium. New RFLPs for albumin and alcohol dehydrogenase detected with this technique are described. PMID- 2885258 TI - Biochemical and genetic exclusion of calmodulin as the site of the basic defect in cystic fibrosis. AB - Recent physiological studies have shown a defective beta-adrenergic regulation of chloride transport and protein secretion in tissues affected by cystic fibrosis. The exact biochemical nature of this abnormality is unknown, but an intracellular second messenger may be involved. We have tested the hypothesis that calmodulin is the site of the basic defect in CF using biochemical and molecular genetic techniques. We report here that there is no gross structural abnormality in the calmodulin protein from CF submandibular glands, and that although there are at least three distinct sequences that cross-hybridise with a calmodulin cDNA probe in the human genome, none of these can be the locus of CF. A polymorphism at the locus of a calmodulin cross-hybridising sequence at human chromosome 7p2 is described. PMID- 2885259 TI - Assignment of the human gamma-glutamyl transferase gene to the long arm of chromosome 22. AB - We have determined the chromosomal location of the human gene for gamma glutamyltransferase (GGT). This study was done by in situ hybridization of human metaphase spreads with a rat cDNA probe specific for this enzyme and constructed from two clones previously characterized in our laboratory. The final construct had a 1.6-kb-long insert covering 92% of the coding sequence for GGT. The new insert was also freed of any GC tails introduced for the cDNA cloning, because we observed that these sequences were responsible for a high background. Using this probe for the analysis of 136 human metaphase spreads, we observed a strong specific signal on chromosome 22 at the interface of q111-112 and a minor peak in q131. Thus GGT might represent a new marker for the study of certain diseases which have chromosomal abnormalities at these loci. PMID- 2885260 TI - Quantifying side-effects of beta-blockers: the role of visual analogue scales. AB - Beta-blockers are often prescribed for patients who are asymptomatic and for whom the benefits of therapy are likely to be small. Side-effects are therefore of great importance. Symptoms such as muscle fatigue and peripheral coldness are commonly associated with treatment with beta-blockers but these subjective phenomena are difficult to detect and quantify so that their prevalence and severity are uncertain. Conventional symptom questionnaires may be relatively insensitive and visual analogue scales (VAS), which permit interval quantification of subjective phenomena, may have some advantages. They appear to be able to detect the presence of tiredness of the legs and peripheral coldness among hypertensive patients taking beta-blockers and are more sensitive than descriptive or 'category' questionnaires. However, some patients find VAS hard to understand and a minority of patients score erratically for all symptoms. A most detailed explanation is of paramount importance. Scores derived from VAS surveys are not normally distributed and should be examined using non-parametric statistical methods; normalising transformations do not improve the sensitivity of the method. PMID- 2885262 TI - Immobilization of microbial cells in gelatine using gamma-irradiation. PMID- 2885261 TI - Radioimmunolocation of a heterotransplanted human choriocarcinoma (BeWo) using monoclonal anti-SSEA-1: pharmacokinetics. AB - Stage-Specific Embryonic Antigen-1 (SSEA-1), originally discovered on mouse teratocarcinomas, has since been found on some human non-seminomatous germ-cell tumors and adenocarcinomas, as well as on some adult mouse and human tissues. A monoclonal antibody to this antigen (anti-SSEA-1; IgM, kappa) was used for radioimmunolocation. Nude mice bearing the human choriocarcinoma BeWo, which is SSEA-1 positive, were injected using a mixture of [131I]anti-SSEA-1 and [125I]MOPC 104E, an unselected myeloma protein of the same heavy-chain isotype. Animals were sacrificed at 24 hour intervals; the radioactive deposition due to both antibodies was determined for both tumors and normal organs. Accumulation of anti-SSEA-1 in the tumor was consistantly rapid and specific, while little accumulation of the unselected myeloma protein occurred. At five days after injection, an average of 3% of the initial dose of specific antibody was retained per gram of tumor; the tumor/blood ratio was 11, tumor/muscle was 80. Gamma camera imaging allowed ready location of the tumors. Tumors could also be imaged using F(ab')2 antibody fragments. PMID- 2885264 TI - Release of Thy-1 from human and murine T-cell lines by a specific phospholipase. AB - Proteins on the outer surface of cultured human and murine lymphoblastoid T cells were labelled with 125I. The labelled cells were incubated with the enzyme phosphatidylinositol-specific phospholipase C (PI-PLC). Proteins cleaved from the cell membrane by the enzyme were immunoprecipitated with anti-Thy-1 antibodies, separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE), and identified by autoradiography. A doublet of Thy-1 bands of approximately 16,000 daltons were detected. The result suggests that: Thy-1 is present on the human and murine T cells which we tested, and Thy-1 is attached to the cell membrane via a phosphatidylinositol domain. PMID- 2885263 TI - Assignment of the Ly-6--Ril-1--Sis--H-30--Pol-5/Xmmv-72--Ins-3--Krt-1--Int-1 - Gdc-1 region to mouse chromosome 15. AB - Previous work has demonstrated linkage between Ly-6, H-30, and a locus, Ril-1, that affects susceptibility to radiation-induced leukemia. Results or preliminary linkage analyses suggested further that the cluster might be linked to Ly-11 on the proximal portion of mouse chromosome 2. Using molecular probes to examine somatic cell lines and recombinant inbred and congenic strains of mice, we have re-evaluated these linkage relationships. A cloned genomic DNA fragment derived from a retroviral site has been used to define a novel locus, Pol-5, that is tightly linked to both H-30 and Ril-1 as shown by analysis of the B6.C-H-30c congenic mouse strain. Following the segregation of the Pol-5 mouse-specific DNA fragment in a series of somatic cell hybrids carrying various combinations of mouse chromosomes on a rat or Chinese hamster background mapped Pol-5 to mouse chromosome 15. During the course of these studies, restriction fragment length polymorphisms were defined associated with several loci, including Pol-5, Ly-6, Sis, Ins-3, Krt-1, Int-1, and Gdc-1. Three of these loci, Sis, Int-1, and Gdc-1, have been previously mapped to chromosome 15 by others using somatic cell hybrids or isoenzyme analyses. Following the inheritance of these eight loci in recombinant inbred strains of mice allowed the definition of a linkage group on the chromosome with the order Ly-6--Ril-1--Sis--H-30--Pol-5--Ins-3--Krt-1--Int-1- Gdc-1. Analyses of alleles inherited as passengers in B6.C-H-30c, C3H.B-Ly-6b, and C57BL/6By-Eh/+ congenic mouse strains and in situ hybridization experiments support the above gene order and indicate further that the cluster is located on distal chromosome 15, with Ly-6 and Sis near Eh. PMID- 2885265 TI - Evaluation of three formulations of a chitin synthesis inhibitor (fenoxycarb) against mosquito vectors. PMID- 2885266 TI - Evaluation of a synthetic pyrethroid (cyfluthrin) for insecticidal activity against different mosquito species. PMID- 2885267 TI - Changes in some intestinal enzyme activities in experimental hexachlorobenzene induced porphyria and modifying effects of diet. AB - Some diets exert a considerable influence on porphyrin metabolism and induction of microsomal liver enzymes in experimental porphyria induced by hexachlorobenzene (HCB). As HCB and its metabolites come into direct contact with intestinal mucosa, this study investigated the changes in the activities of intestinal disaccharidases and gamma-glutamyl transferase in a model of HCB induced porphyria. The effects of different diets on enzymatic activities during HCB intoxication were also studied. HCB was administered by gastric tube at 3.5 mmol/kg body weight daily for 90 and 61 days. HCB intoxication strongly diminished the activities of intestinal lactase, maltase, sucrase, cellobiase and trechalase. Carbohydrate diets (with 78 weight % glucose or starch), given simultaneously with HCB treatment, exerted a protective effect on disaccharidase activities. These regimens maintained cellobiase and trechalase within the normal levels and even increased maltase. High-fat/high-protein diets (with 30% either butter or sunflower oil and 31% casein) aggravated the decrease of all disaccharidases. In contrast with the decrease in disaccharidase activity, intestinal gamma-glutamyl transferase was increased, suggesting multiple mechanisms for the action of HCB intoxication on the intestinal enzyme system. Diet had a pronounced modifying effect. PMID- 2885268 TI - Cardiovascular and renal profile of acute peripheral dopamine1-receptor agonism with fenoldopam. AB - Whether the dopaminergic system may be involved in essential hypertension is of pathogenetic as well as therapeutic interest. Therefore, we investigated in eight hypertensive and 12 normal subjects cardiovascular, endocrine, and renal responses to fenoldopam, which has been characterized experimentally as an agonist of peripheral postsynaptic dopamine1 receptors. A single oral dose of fenoldopam, 100 mg, changed blood pressure (BP) in hypertensive subjects (from 163/103 to 147/76 mm Hg; p less than 0.01 for systolic and p less than 0.001 for diastolic BP) and normal subjects (from 121/81 to 123/65 mm Hg; p less than 0.001 for diastolic BP); percentage decreases in diastolic BP averaged -20 +/- 6 and 16 +/- 7%, respectively. Fenoldopam-induced effects on other variables were similar in the two groups. Heart rate rose (p less than 0.001) on average from 69 to 92 beats/min in hypertensive and from 64 to 84 beats/min in normal subjects. Effective renal plasma flow increased (from 552 to 765 and 634 to 937 ml/min/1.73 m2; p less than 0.01), while glomerular filtration rate tended to decrease (from 121 to 99 ml/min/1.73 m2 in the hypertensive and from 119 to 97 ml/min/1.73 m2; p less than 0.001 in the normal group). Fractional sodium clearance was elevated (from 2.8 to 5.2 and 1.7 to 3.8%; p less than 0.01), as was free water clearance (from -1.7 to 0.6 and -1.7 to 0.1 ml/min/1.73 m2; p less than 0.01). Potassium clearance was largely unchanged. Plasma renin activity increased about twofold (p less than 0.01 in normal subjects), and plasma aldosterone by 40% (NS). Plasma norepinephrine levels increased twofold to 2.5-fold (p less than 0.001), and urinary norepinephrine excretion fivefold to 10-fold (p less than 0.01). Fenoldopam-induced changes were not significantly modified by intravenous and/or oral pretreatment with the dopamine-receptor antagonist metoclopramide or the cyclooxygenase inhibitor indomethacin. These findings suggest that in humans, fenoldopam may acutely override the dopaminergic antagonism of metoclopramide given in clinical dosage and that its cardiovascular and renal effects are not prostaglandin-mediated. Although acute sympathetic stimulation may be partially antagonistic, the concomitant BP-lowering, renal vasodilating, and natriuretic actions of fenoldopam represent a desirable profile of a potential antihypertensive agent. PMID- 2885269 TI - Conversion of B1 kinin receptor-mediated vascular relaxation to contraction. AB - We have previously reported that des-Arg9-bradykinin can relax the phenylephrine precontracted rabbit mesenteric artery through B1 kinin receptor stimulation and the subsequent release of prostaglandins. In the present study, we have found that this relaxant response can be converted to a contractile response by the cyclooxygenase inhibitor indomethacin. Contraction was dose-dependent and was blocked by the B1 receptor antagonist [Leu8]des-Arg9-bradykinin, with a pA2 value obtained by Schild regression similar to that reported for relaxation in the absence of indomethacin. Des-Arg10-kallidin (ED50 = 5.0 +/- 0.9 X 10(-9) M) was 16 times more potent than des-Arg9-bradykinin (ED50 = 8.1 +/- 0.8 X 10(-8) M) in contracting the indomethacin-treated artery and was also blocked by [Leu8]des Arg9-bradykinin. In contrast, only 13 out of 24 indomethacin-treated vessels contracted in response to bradykinin, which had only one tenth and one 160th the potency (ED50 = 9.9 +/- 1.8 X 10(-7) M) of des-Arg9-bradykinin and des-Arg10 kallidin, respectively. B1 kinin receptor-mediated contraction in the presence of indomethacin was unaffected by the dual cyclooxygenase-lipoxygenase inhibitor BW 755c. These results indicate that des-Arg-kinins can stimulate both relaxation and contraction of the phenylephrine-precontracted rabbit mesenteric artery through stimulation of B1 kinin receptors. The relaxation is dependent on the release of prostaglandins, while the contraction may represent a direct effect. PMID- 2885271 TI - Prazosin-induced alterations in renal alpha-adrenergic receptor function. AB - Chronic (3-day) treatment with prazosin causes an increase in renal alpha 2 adrenergic receptor density and the relocation of renal tubular alpha 2 adrenergic receptors from extrajunctional to postjunctional sites. We investigated whether chronic prazosin treatment (2 mg/kg, i.p.) caused a functional alteration of other renal alpha 2-adrenergic receptors, using the isolated perfused rat kidney. Prazosin significantly reduced blood pressure and increased heart rate during the 3-day treatment. Renal nerve stimulation (2-8 Hz, 10 V, 1 msec) caused a frequency-dependent increase in renovascular resistance, which was potently blocked by prazosin in vitro in both control and prazosin treated rat kidneys. The vasoconstrictor response to the alpha 2-adrenergic receptor-selective agonist BHT 933 (3-300 microM) was significantly higher in kidneys from prazosin-treated rats. Yohimbine (3-300 nM) potentiated the response to renal nerve stimulation in both treatment groups. The increase in vascular resistance following renal nerve stimulation was lower in kidneys from prazosin treated rats, but the response to the alpha 1-adrenergic receptor agonist methoxamine (0.3-1 microM) was unchanged. Further studies revealed that renal nerve stimulation-evoked norepinephrine release from prazosin-treated rat kidneys was significantly lower than release from untreated controls. This response could be normalized to control levels by a combination of cocaine (10 microM) and yohimbine (100 nM). Thus, chronic prazosin treatment caused enhanced alpha 2 adrenergic receptor-mediated vasoconstriction and facilitated renal prejunctional inhibitory mechanisms. We conclude that with chronic alpha 1 adrenergic receptor blockade there is increased alpha 2-adrenergic receptor function in at least two and possibly three sites in the kidney; these include postjunctional tubular, prejunctional vascular, and possibly extra-junctional vascular sites. PMID- 2885270 TI - Synthesis and characterization of arylamine derivatives of rauwolscine as molecular probes for alpha 2-adrenergic receptors. AB - The selective alpha 2-adrenergic receptor antagonist rauwolscine was structurally modified to yield a series of arylamine carboxamide derivatives, which were investigated as potential molecular probes for the localization and structural characterization of alpha 2-adrenergic receptors. The arylamine carboxamides differ in the number of carbon atoms separating the reactive phenyl moiety from the fused ring structure of the parent compound, rauwolscine carboxylate. Competitive inhibition studies with [3H]rauwolscine in rat kidney membranes indicate that the affinity for the carboxamide derivatives is inversely related to the length of the carbon spacer arm with rauwolscine 4-aminophenyl carboxamide (zero carbon spacer arm; rau-AMPC) exhibiting the highest affinity (Kd = 2.3 +/- 0.2 nM). Radioiodination of rau-AMPC yields a ligand, 125I-rau-AMPC, which binds to rat kidney alpha 2-adrenergic receptors with high affinity, as determined by both kinetic analysis (Kd = k2/k1 = 0.016 min-1/2.1 X 10(7) M-1 min-1 = 0.76 nM) and equilibrium binding studies (Kd = 0.78 +/- 0.16 nM). 125I-rau-AMPC was quantitatively converted to the photolabile arylazide derivative 17 alpha-hydroxy 20 alpha-yohimban-16 beta-(N-4-azido-3-[125I]iodophenyl) carboxamide (125I-rau AZPC). In a partially purified receptor preparation from porcine brain, this compound photolabels a major (Mr = 62,000) peptide. The labeling of this peptide is inhibited by adrenergic agonists and antagonists with a rank order of potency consistent with an alpha 2-adrenergic receptor binding site. Both 125I-rau-AMPC and the photolabile arylazide derivative, 125I-rau-AZPC, should prove useful as molecular probes for the structural and biochemical characterization of alpha 2 adrenergic receptors. PMID- 2885272 TI - High calcium diet reduces blood pressure in Dahl salt-sensitive rats by neural mechanisms. AB - We tested the hypothesis that high dietary calcium attenuates hypertension in Dahl salt-sensitive rats by neural as opposed to vascular mechanisms. Four-week old Dahl salt-sensitive rats were fed a high salt diet (3.3% sodium) with either high (4.0%; n = 21) or normal (0.4%; n = 21) calcium content until they were 10 to 11 weeks old. Total plasma calcium concentration was increased and plasma phosphorus concentration was decreased by the high calcium diet. At 10 weeks, food intake and intestinal absorption of sodium were not altered by the high calcium diet. There were three major observations. First, mean arterial pressure was lower in awake rats fed a high versus normal calcium diet (137 +/- 7, n = 11, vs 165 +/- 6 mm Hg, n = 10, respectively; p less than 0.05). This pressure difference was dependent on intact autonomic transmission, since ganglionic blockade eliminated the significant difference between pressures in rats fed high (78 +/- 5 mm Hg) and normal (85 +/- 6 mm Hg) calcium diets. Second, high calcium intake augmented baroreceptor reflex inhibition of renal sympathetic nerve activity and heart rate during ramp increase in arterial pressure produced by infusion of phenylephrine. Reflex suppression of renal sympathetic nerve activity was twofold greater in rats fed the high (vs normal) calcium diet (-2.79 +/- 0.25 vs -1.34 +/- 0.14% delta/delta mm Hg, respectively; n = 9 rats per group; p less than 0.05). Third, high calcium intake did not attenuate vascular responsiveness, since pressor responses to norepinephrine and angiotensin II did not differ between rats fed high and normal calcium diets after ganglionic blockade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885273 TI - Neurohumoral and hemodynamic responses to dietary calcium supplementation in deoxycorticosterone-salt hypertensive dogs. AB - We determined whether dietary calcium supplementation can influence the development and maintenance of hypertension in deoxycorticosterone (DOC)-salt treated dogs. Dogs on normal dietary calcium (0.4%) had significant increases in mean arterial pressure (from 92 +/- 2 to 131 +/- 3 mm Hg, p less than 0.01); those given high dietary calcium (1.7%) had attenuated but significant increases in mean arterial pressure (from 90 +/- 2 to 107 +/- 1, p less than 0.01). The elevation of blood pressure in dogs on normal dietary calcium was primarily due to increased calculated total peripheral resistance, which was prevented by the high calcium diet. The increases in blood pressure could not be attributed to any changes in cardiac output, blood volume, or plasma norepinephrine. These results suggest that mineralocorticoid hypertension in the dog is associated with abnormalities not only in sodium, but also in calcium metabolism. Further, they suggest a direct link between sodium and calcium metabolism and may thus have implications for the pathogenesis and management of salt-dependent hypertension. PMID- 2885274 TI - The area postrema in deoxycorticosterone-salt hypertension in rats. AB - Ablation of the area postrema in rats prevents sustained hypertension during angiotensin II infusion and after unilateral renal artery constriction (two kidney, one clip hypertension). The current experiment was performed to determine whether an intact area postrema is required for hypertension development in a low renin model of experimental hypertension in rats. In 11 rats, the area postrema was destroyed using electrical current; the extent and specificity of each lesion was confirmed later by blind histological analysis. In 12 rats, sham operations were performed. All rats were uninephrectomized and drank saline. During once weekly injections of deoxycorticosterone pivalate (5 mg/wk) for 4 weeks, sham operated rats (n = 10) showed a significant increase in mean arterial pressure (Days 6-28) and saline intake (Days 12-28), but no significant increase in sodium or water retention. Deoxycorticosterone-treated rats with area postrema ablation (n = 9) exhibited no change in arterial pressure, sodium retention, or water retention, but a significant increase in saline intake (Days 17-28). Plasma renin activity was equally suppressed in both groups of rats. The depressor response to ganglion blockade with hexamethonium (20 mg/kg i.v.) was significantly increased during the 2nd, 3rd, and 4th weeks of steroid treatment in sham-operated, but not area postrema-ablated, rats. Four rats (2 sham-operated; 2 ablated) showed no change in any variable over 28 days in the absence of steroid treatment. It is concluded that the area postrema may be important in some non-angiotensin dependent forms of experimental hypertension, possibly by affecting neurogenic control mechanisms. PMID- 2885275 TI - Role of alpha 1- and alpha 2-adrenergic receptors in the human hypertensive kidney. AB - Since it is not known for certain which alpha-adrenergic receptors mediate renal vasoconstriction in human essential hypertension, we infused either doxazosin (n = 7) or yohimbine (n = 7) into the renal arteries of hypertensive subjects immediately prior to diagnostic angiography. Both agents caused an increment in renal blood flow as assessed with the xenon-washout technique. Doxazosin increased renal flow from 342 +/- 36 to 360 +/- 55 ml/min per 100 g (0.05 less than p less than 0.10). Yohimbine enhanced flow from 380 +/- 41 to 485 +/- 63 ml/min per 100 g (p less than 0.01). The effect of yohimbine was significantly greater than that of doxazosin. In a control group (n = 7) receiving only saline, no changes in renal blood flow occurred. Doxazosin enhanced renin secretion in the kidney by 10 +/- 4% over levels in controls (0.05 less than p less than 0.10), whereas yohimbine increased renin release by 80 +/- 23% (p less than 0.01). The latter increase was apparently not due to alterations in flow alone, since the arteriovenous gradient for renin also widened. We conclude that in resting conditions, neurogenic vascular tone in the kidney depends mainly upon activation of alpha 2-adrenergic receptors. Moreover, these receptors exert a tonic inhibitory influence on renin release. PMID- 2885276 TI - Antigenic analysis of Serratia marcescens fimbriae with monoclonal antibodies. AB - Monoclonal antibodies (MAbs) were raised against the purified fimbriae of Serratia marcescens US46, a strain expressing three morphologically distinct fimbriae. The widths of these fimbriae were 7, 4.5, and 3 nm, respectively. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified fimbriae showed three bands with molecular weights of 21,000, 20,000, and 19,000, respectively. This strain had mannose-resistant (MR) hemagglutinating activity and was agglutinated by yeast cells. Therefore, strain US46 appeared to have both MR and mannose-sensitive fimbriae. In the immunoblot analysis, all MAbs reacted with the 20,000-molecular-weight subunit when given a choice of three differently sized subunits. Immunoelectron microscopy showed these MAbs attached to the MR fimbriae with the largest width (7 nm). The antigenic cross-reactivity of fimbriae was examined by an MAb-mediated agglutination test. All MR strains of S. marcescens and some mannose-sensitive strains were agglutinated by the MAbs. The serological homogeneity of MR fimbriae was confirmed by a spot test, using the crude purified fimbriae from several MR strains of S. marcescens. In other gram negative rods, clinical isolates of Klebsiella spp. with hemagglutinating activity were agglutinated, but clinical isolates of Escherichia coli and Enterobacter spp. were not. PMID- 2885277 TI - Temperature-dependent transcriptional regulation of expression of fimbriae in an Escherichia coli strain isolated from a child with severe enteritis. AB - Escherichia coli 469-3 synthesizes fibrillar fimbriae at 37 degrees C, but not at 18 degrees C, which promote its adherence to human colonocytes. RNA homologous with a cloned fragment of the strain 469-3 chromosome necessary for normal expression of fimbriae was virtually undetectable in bacteria grown at 18 degrees C, indicating that environmental temperature affects expression by regulating transcription. PMID- 2885278 TI - In vitro susceptibility of different human T-cell subpopulations and resistance of large granular lymphocytes to HTLV-I infection. AB - T4 subpopulation of T lymphocytes is the preferential target of infection with human T leukemia/lymphoma virus of subgroup I (HTLV-I). In this study we attempt to determine whether different T-cell subsets exhibit differences in susceptibility to virus infection. T cells from cord or peripheral blood were separated according to cell densities and T-cell surface markers by Percoll gradient and Sepharose anti-Fab immunoadsorbent affinity column (IAC), respectively. Separated T-cell subpopulations were infected with HTLV-I, by means of co-cultivation with irradiated virus producer cell lines (MT-2, TK). Percentages of HTLV-I-infected cells were assayed by immunofluorescence assay (IFA), using highly specific mouse monoclonal antibody (MAb) directed against HTLV-I p19 core protein. The results showed that different T-cell subpopulations separated either by Percoll or by IAC were susceptible to HTLV-I infection with the exception of large granular lymphocytes (LGL), which exhibit high cell mediated natural cytotoxicity (CMNC). The susceptibility to HTLV-I infection of T cells with CMNC activity was further studied on established cell clones with LGL morphology. The results showed again that these cells were resistant to the virus infection. The present studies indicate that different T-cell subpopulations, irrespective of their size and of cell-surface markers, are susceptible to HTLV-I infection, with the exception of functionally mature LGL or of immortalized LGL clones. PMID- 2885279 TI - A rat monoclonal antibody 4D7 produced by a hybridoma established from a yolk-sac tumor-bearing rat binds selectively to the stage-specific embryonic antigen SSEA 1. AB - A monoclonal rat IgM (kappa) antibody (MAb) is produced by a hybridoma obtained by fusion of the rat myeloma Y3 Ag 1.2.3 with spleen cells from a female W/Fu rat bearing a yolk-sac carcinoma isograft. In the rat this antibody (4D7) shows strong selective binding to all tested yolk-sac carcinomas, but no binding to cultured cells of a number of other tumor types or to cells of normal tissues. Immunohistochemical analysis of the specificity of the antibody confirmed the strong binding to yolk-sac carcinomas and also revealed binding to some other rat tissues. These include one colon carcinoma, the embryonic ectoderm and the primitive visceral endoderm of 8.5-day-old embryos, the central nervous system and the oviduct epithelium and some cells in the seminal tubules, the gastrointestinal epithelium and associated mucus and also the distal tubuli and collecting ducts of the kidney. The MAb binds strongly to purified SSEA-1 but not to purified Lewis A glycolipid. It is concluded that the 4D7 MAb recognizes a determinant which is identical to or includes Gal beta 1-4(Fuc alpha 1-3) GlcNAc. The immunogenicity of the SSEA-1 determinant is further confirmed by the demonstration that antibodies binding to purified SSEA-1 but not to Lewis A appear in the sera of some of the rats developing primary yolk-sac carcinoma. PMID- 2885280 TI - Appearance of serum antibodies to rat yolk-sac carcinomas during the latent period prior to primary tumor development. AB - Rat yolk-sac tumors were induced by intraperitoneal (i.p.) displacement of the visceral yolk sac in fetectomized W/Fu rats. Serum was obtained from each female rat prior to the pregnancy preceding the tumor-inducing procedure and then once a month during the induction period. The sera were analyzed for the presence of antibodies binding to cultured cells of one of the yolk-sac tumors. Sera were also assayed for complement-dependent cytotoxic antibodies on tumor cells. In rats that developed tumors, antibodies reacting specifically with the target tumor cells could be detected in all of 10 rats. Antibodies appeared before tumor detection in all animals but one, and in 6 rats as early as 11 to 25 weeks prior to tumor detection. Nine rats developed antibodies demonstrable in the binding assay and in 6 of those the antibodies appeared 8 to 25 weeks before the tumor became palpable. Analysis of the isotypes of the Ig that bound to tumor cells showed that IgG1 and IgG2b were most frequently present. In one rat IgG2a antibodies appeared one month before tumor detection followed by IgG1 and IgG2b antibodies detectable 4 weeks later. IgG2c and IgM antibodies were not detected in any of the rats. At dilution 1/10, sera of all 10 rats showed specific cytotoxicity to the tumor cells in the presence of added rabbit complement. In 9 of these animals antibodies were demonstrated 1 to 4 months prior to tumor detection. PMID- 2885281 TI - Prolactin response to clomiphene citrate is different in hyperprolactinemic polycystic ovary syndrome and idiopathic hyperprolactinemia. PMID- 2885282 TI - Progesterone therapy to decrease first-trimester spontaneous abortions in previous aborters. AB - A study was designed to see if the use of prophylactic progesterone vaginal suppositories (PVS) reduced the risk of spontaneous abortions in women with a history of at least one spontaneous abortion. PVS was employed during the luteal phase to the end of the first trimester. The dosage was initially 50 mg/day, but was increased according to the endometrial biopsy and doubled as soon as pregnancy was established. Only 10 women (10%) aborted, and 8 of these 10 were successful in their next PVS-treated pregnancies. Overall there were 12 losses in 132 pregnancies (9%) in these PVS-treated patients. Forty-two percent of untreated controls aborted (10/24). The results suggest that PVS is effective in reducing the risk of spontaneous abortions in high-risk patients. PMID- 2885283 TI - Acyclovir treatment of twelve unexplained infertile couples. AB - Because of recently published research showing herpes antibodies in the endometria of patients who had aborted, as well as evidence of subacute inflammation of the endometria, 17 couples suffering from long-standing totally unexplained infertility (except for persistent subacute inflammation of the endometrial were given acyclovir over a period of six menstrual cycles. Five of these couples did not complete the treatment protocol. Of the 12 couples who did, 5 became pregnant, with successful pregnancies. Two of the five had posttreatment endometrial biopsies that were negative, and both became pregnant subsequently. In contrast to their past histories, there were no spontaneous abortions. PMID- 2885284 TI - Pelvic pathology affecting fertility. PMID- 2885286 TI - Lower lifetime occurrence of breast cancer and cancers of the reproductive system among former college athletes. AB - The prevalence (lifetime occurrence) rate of cancers of the reproductive system (uterus, ovary, cervix, and vagina) and breast was determined for 5,398 living college alumnae, 2,622 of whom were former college athletes and 2,776 nonathletes, from data on medical and reproductive history, athletic training, and diet. The former athletes had a significantly lower risk of cancer of the breast and reproductive system than did the nonathletes. The relative risk (RR), nonathletes/athletes, for cancers of the reproductive system was 2.53, 95% confidence limits (CL) (1.17, 5.47). The RR for breast cancer was 1.86, 95% CL (1.00, 3.47). The analysis controlled for potential confounding factors, including age, family history of cancer, age at menarche, number of pregnancies, use of oral contraceptives, use of estrogen in the menopausal period, smoking, and leanness. Of the college athletes, 82.4% had been on precollege teams compared with 24.9% of the college nonathletes. We conclude that long-term athletic training lowers the risk of breast cancer and cancers of the reproductive system. The lowered risk may be related to changes in estrogen metabolism associated with increased leanness. PMID- 2885285 TI - Sperm velocity, pre- and post-washing, as a measure of the effects of varicocelectomy and subsequent male fertility. AB - Although the beneficial effect of varicocelectomy on subsequent fertility rates in subfertile men with varicocele is well documented, the effect of the dysfunction on spermatozoal fertilizing capability in this disorder remains unclear. This prospective study was conducted to determine whether sperm velocity and other quantitative semen parameters in the fresh ejaculate and after washing correlate with subsequent fertility. The authors investigated semen characteristics in 25 men with varicoceles, before and 6 months after varicocelectomy. A significant (P less than .01) correlation was observed between postvaricocelectomy improvement in sperm velocity in the fresh ejaculate and fertility. A significantly higher correlation (P less than .001) was observed between varicocele repair and improved velocity in washed, incubated sperm. No pregnancies occurred in the wives of men whose postwash sperm velocity failed to improve following surgery. It is suggested that varicocelectomy may enhance or restore the ability of spermatozoa to undergo capacitation. One may conclude that sperm velocity correlates significantly with future fertility, and that the velocity of washed, incubated sperm is the more specifically predictive evaluative measure of fertilizing capability in males who have undergone varicocele repair. PMID- 2885287 TI - Tamoxifen in clomiphene-resistant hypothalamic anovulation. AB - Seventeen patients with clomiphene-resistant hypothalamic anovulation were given tamoxifen 10 mg per day from cycle day 5 to 9 during two consecutive menstrual cycles. Not included were patients with hyperprolactinemia and PCOD. Treatment was monitored using measurement of follicle size by ultrasound and assessment of serum estradiol. Failure to ovulate persisted in 15 patients. Of the two patients who ovulated, one received hCG on day 16, and became pregnant. We were unable to demonstrate that clomiphene-resistant patients were likely to ovulate with tamoxifen. Forty-five patients with hypothalamic anovulation not previously treated were then given tamoxifen in the same dosage. This part of the study indicated that tamoxifen was successful in inducing ovulation in 84% of the cycles. There was marked improvement in cervical mucus in tamoxifen cycles as compared with clomiphene cycles. Tamoxifen was effective, and had some advantages compared with clomiphene in patients responding to both drugs. This preliminary study suggests that tamoxifen may be a useful addition to the treatment of ovulatory failure. PMID- 2885288 TI - Acute pelvic inflammatory disease: a clinical follow-up. AB - One hundred eighty-two women were diagnosed by laparoscopy as having an initial episode of acute pelvic inflammatory disease (PID). The classification of PID was based on a modification of Westrom's criteria. Antibiotic treatment followed recommended protocols established by the Centers for Disease Control (CDC). Each year, the woman is contacted to complete a questionnaire detailing her reproductive history, presence of pelvic pain, and menstrual history, as well as other miscellaneous gynecologic history. The study covers a follow-up interval of six months to 8 years. The results are categorized according to the severity of the acute PID, as well as the time elapsed since the infection. A psychological investigation of post-PID pain was performed, and yielded accurate prediction of whether or not pain had been reported by a patient during the acute phase of the disease. Results indicate an increased incidence of involuntary sterility as the disease progresses in severity. The occurrence of ectopic pregnancy is increased for all stages of PID, but most particularly, following tubo-ovarian abscess. The long-term consequences of a single episode of acute PID are often severe. PMID- 2885289 TI - Laparoscopic oophorectomy and salpingo-oophorectomy in the treatment of benign tubo-ovarian disease. AB - Laparoscopic oophorectomy or salpingo-oophorectomy was performed in 24 women using bipolar coagulation followed by scissors division of the infundibulopelvic ligament, the utero-ovarian ligament, and the broad ligament. Indications were pelvic pain secondary to ovarian adhesions from previous hysterectomy (nine cases, four with palpable masses), pelvic pain secondary to ovarian endometrioma (six cases, three with endometrioma greater than 10 cm); postmenopausal palpable ovary (five cases); pelvic mass secondary to dermoid cyst (one case); pelvic pain and mass secondary to large hydrosalpinx and ovarian endometrioma (two cases), and bilateral ovarian ablation for autoimmune disease (one case). There were no intraoperative or late complications. Relative safety of the procedure is acknowledged, with emphasis placed on meticulous surgical technique and knowledge of retroperitoneal anatomy. PMID- 2885290 TI - The use of CO2 laser laparoscopy for treating endometriosis. AB - The utilization of CO2 laser laparoscopy has become an increasingly accepted procedure because of its ability to obviate the need for major surgery. The accuracy of the laser beam through its delivery system, in addition to minimal tissue damage without injury to adjacent structures, makes it ideal for treating minimal and moderate endometriosis. Its use in individuals with endometriosis may render unnecessary other medical treatments, since therapy can be performed at the same time that the disease is found. This therapy appears to be as successful as medical treatment, or more so, since 76% of patients with minimal disease as the only explainable fertility problem became pregnant after treatment. The advantages of this tool for treatment of endometriosis include high success rate, immediate treatment with a very small increase of operating room time, and the ability to treat certain conditions accompanying endometriosis which cannot be accomplished with medicine alone (e.g., adhesions). PMID- 2885291 TI - Alterations in blood sugar, protein, and lipid levels in Indian women by norethisterone enanthate. AB - Fasting levels of sugar, protein, and lipids, namely, cholesterol, triglyceride, and phospholipid, were determined in the blood of 150 women taking an injectable contraceptive, norethisterone enanthate, 200 mg every 60 days for 24 months. Triglyceride and cholesterol showed a statistically significant decrease from 10 and 16 months of use; however, both values returned to control level after use for 24 months. Serum phospholipids and total protein did not show significant changes, while the blood sugar level increased significantly from 12 months onwards and remained elevated (P less than .001) up to the end of the trial period. PMID- 2885292 TI - The etiology in 77 primary amenorrhea patients. AB - This study is based upon an analysis of 77 cases of primary amenorrhea. The work up included a complete endocrinological study, cytogenetics, laparoscopy, and gonadal biopsy. Of the total number of patients, 31 had a completely developed female phenotype, 22 had an insufficiently developed one, and the remaining 24 patients were characterized by infantilism. A positive sex chromatin was obtained in 59 patients, and negative in 18. Out of 77 patients, 25 had an abnormal karyotype or one corresponding to the opposite sex. In six patients, the existence of a Y chromosome in the karyotype was found in spite of the female phenotype. Five patients had the testicular feminisation syndrome. PMID- 2885293 TI - Conjugates of catecholamines. VII. Synthesis and beta-adrenergic activity of peptide catecholamine conjugates. AB - A series of novel catecholamine derivatives has been prepared in which one of the N-methyl substituents of isoproterenol has been extended by a spacer consisting of a chain of four methylenes which terminates with an amide linkage to a peptide, the point of attachment being via the aromatic amino group of p aminophenylalanine. In one of the derivatives, two catecholamines are attached to the same peptide in this manner. The peptides, which range in size from three to eight amino acid residues and contain phenylalanine, glycine, and L-alpha-amino delta-hydroxyvaleric acid, were synthesized via stepwise and fragment condensation techniques. The beta-adrenergic agonist activities of the derivatives were evaluated in vitro by measuring the intracellular accumulation of cyclic AMP in S49 mouse lymphoma cells. PMID- 2885294 TI - Neuroleptic malignant syndrome: a patient report. PMID- 2885295 TI - 125I-iodinated benzazepines bind to melanin: implications for the noninvasive localization of pigmented melanomas. AB - Both the 5-R and the 5-S enantiomers of [125I]2,3,4,5-tetrahydro-8-iodo-3-methyl 5-phenyl-1H-3-benzazepin- 7-ol bind to melanin. The interaction between the 5-R enantiomer and melanin permits visualization of melanomas in mice with a noninvasive imaging procedure. Two lines of evidence suggest that the interaction between iodinated ligands and melanin is not related to the D-1 dopamine receptor, a known target for the 5-R enantiomer: first, melanin binds both enantiomers of the 125I-iodinated benzazepine while the D-1 receptor binds only the 5-R enantiomer; second, the melanin binding site displays only a 5-fold difference in affinity towards the R- and S-enantiomers of SCH 23390 while the D 1 receptor displays a 100-fold difference in affinity towards these two molecules. Because both enantiomers of the iodinated benzazepine bind to a human pigmented melanoma, we propose that such compounds may be of use in the diagnosis of pigmented melanoma: in addition, we discuss the possible application of these molecules as a supplement to existing technology for the localization of pigmented melanomas. PMID- 2885296 TI - Immunoelectron microscopic localization of D-amino acid oxidase in rat kidney and liver. AB - The intracellular localization of D-amino acid oxidase in rat kidney and liver has been investigated using the indirect immunogold postembedding technique. Different fixation and embedding conditions for optimal preservation of antigenicity and fine structure have been tested. Immunolabelling was possible only in tissues embedded in polar resins (glycol methacrylate and Lowicryl K4M). In kidney the enzyme was demonstrable only in the peroxisomes of the proximal tubule, where it was associated with the peroxisome core. The enzyme was present in all the peroxisomes of the proximal tubule and appeared to be codistributed with catalase. Control experiments and quantitative analysis confirmed the specificity of the D-amino acid oxidase immunolocalization. All the other cells in kidney failed to demonstrate any labelling. In liver, the immunolabelling was present in the matrix of the hepatocyte peroxisomes, whereas no traces of the enzyme were found in the nucleoid. The intensity of the immunolabelling in liver peroxisomes was lower than in kidney. No specific labelling was observed in cells other than hepatocytes. PMID- 2885298 TI - Effect of beta-adrenergic blockade on thermoregulation during exercise. AB - To resolve conflicting reports concerning the effects of beta-blockade (BB) on thermoregulatory reflexes during exercise, we studied six fit men during 40 min of cycle ergometer exercise at 60% maximum O2 consumption at ambient temperatures of 22 and 32 degrees C. Two hours before exercise, each subject ingested a capsule containing either 80 mg of propranolol or placebo in single-blind fashion. Heart rate at 40 min of exercise was reduced (P less than 0.01) from 125 to 103 beats min at 22 degrees C and 137 to 104 beats min at 32 degrees C, demonstrating effective BB. After 40 min of exercise, esophageal temperature (Tes) was elevated with BB (P less than 0.05) from 37.66 +/- 0.04 to 38.14 +/- 0.03 and 38.13 +/- 0.04 to 38.41 +/- 0.04 degrees C at 22 and 32 degrees C, respectively. The elevated Tes resulted from a reduced core-to-skin heat flux at both temperatures, indicated by a reduction in the slope of the forearm blood flow (FBF)-Tes relationship, and a decrease in maximal FBF. Systolic blood pressure was decreased 20 mmHg with BB (P less than 0.01), whereas diastolic blood pressure was unchanged, reducing arterial pulse pressure (PP). Because PP was decreased and cardiac filling pressure was presumably not reduced (since cardiac stroke volume was elevated), we suggest that at least a part of the relative increase in peripheral vasomotor tone during BB was the consequence of reduced sinoaortic baroreceptor stimulation. PMID- 2885297 TI - Arylsulphatase activity in the oviduct of the frog Rana esculenta. I. Oestradiol induced changes following ovariectomy and hypophysectomy. AB - The effects of oestradiol treatment on arylsulphatase activity in the frog oviduct are reported. Oestradiol-induced changes were also investigated in ovariectomized and hypophysectomized animals. Under all the experimental conditions, hormonal treatment causes an increase in enzyme activity. This can be observed biochemically and also histochemically on frozen sections. Hypotheses are advanced to explain fluctuations in arylsulphatase activity. PMID- 2885300 TI - Control of plasma renin activity in heat-stressed baboons on varied salt intake. AB - The characteristics and control of the increase in plasma renin activity (PRA) during environmental heating (EH) were determined in 12 unanesthetized, chronically catheterized baboons. Each EH experiment consisted of a 1.5- to 4-h exposure to an ambient temperature of 39-44 degrees C until core temperature (Tc) reached 39.5-40.0 degrees C. These EH experiments were done on the baboon in an unblocked state and during beta-adrenergic receptor blockade produced by propranolol when on normal-to-high salt intake (NHSI) and on low-salt intake (LSI). PRA rose linearly with Tc during EH, but the increase in PRA was considerably larger when the baboon was on LSI. The PRA-Tc linear regression coefficients were 2.32 and 5.98 ng angiotensin I X ml-1 X h-1 X degrees C-1 in NHSI and LSI states, respectively. This rise in PRA during EH was completely eliminated during beta-blockade in both NHSI and LSI states. It is concluded that heat stress activates the sympathetic nervous system to stimulate beta-receptor mediated renin secretion by the kidney, this activation is controlled primarily by internal thermoreceptors, and variations in salt intake alters only the magnitude of the increase in PRA during heat stress, not the mechanisms that produce it. PMID- 2885299 TI - Adrenoreceptor effects on rat muscle blood flow during treadmill exercise. AB - The purpose of this study was to examine the effects of the adrenergic receptors on the distribution of blood flow within and among skeletal muscles in rats. Blood flow was measured with the radiolabeled microsphere technique before exercise and during treadmill exercise at 15 or 60 m/min. Alpha- (phentolamine) or beta- (propranolol) adrenergic blocking drugs were administered, and then blood flow was measured and results compared with those from saline-treated rats. Before exercise, alpha-blockade caused increases in total muscle blood flow and in all fast-twitch muscles, whereas muscles composed of greater than 20% slow twitch fibers showed no effect. During exercise at 15 m/min, the normal increase in total muscle blood flow was attenuated by alpha-blockade. Compared with controls, blood flow was less in the high-oxidative (fast and slow) muscle fiber areas of extensor muscles, whereas blood flow to white areas of extensor muscles was increased. beta-Blockade tended to decrease muscle blood flow before exercise and during exercise at 15 m/min with no apparent relationship between the effects of blockade on blood flow and muscle fiber type. These effects of beta-blockade were not apparent during exercise at 60 m/min. We conclude that before exercise alpha-receptor effects are limited to fast muscle, whereas beta-receptor influences are independent of fiber type, beta-receptors contribute to the initial hyperemia of exercise at 15 m/min, and beta-receptor influence is inversely related to metabolic rate. PMID- 2885301 TI - Beta-blockade reduces tidal volume during heavy exercise in trained and untrained men. AB - The effects of beta-blockade on tidal volume (VT), breath cycle timing, and respiratory drive were evaluated in 14 endurance-trained [maximum O2 uptake (VO2max) approximately 65 ml X kg-1 X min-1] and 14 untrained (VO2max approximately 50 ml X kg-1 X min-1) male subjects at 45, 60, and 75% of unblocked VO2max and at VO2max. Propranolol (PROP, 80 mg twice daily), atenolol (ATEN, 100 mg once a day) and placebo (PLAC) were administered in a randomized double-blind design. In both subject groups both drugs attenuated the increases in VT associated with increasing work rate. CO2 production (VCO2) was not changed by either drug during submaximal exercise but was reduced in both subject groups by both drugs during maximal exercise. The relationship between minute ventilation (VE) and VCO2 was unaltered by either drug in both subject groups due to increases in breathing frequency. In trained subjects VT was reduced during maximal exercise from 2.58 l/breath on PLAC to 2.21 l/breath on PROP and to 2.44 l/breath on ATEN. In untrained subjects VT at maximal exercise was reduced from 2.30 l/breath on PLAC to 1.99 on PROP and 2.12 on ATEN. These observations indicate that 1) since VE vs. VCO2 was not altered by beta-adrenergic blockade, the changes in VT and f did not result from a general blunting of the ventilatory response to exercise during beta-adrenergic blockade; and 2) blockade of beta 1- and beta 2-receptors with PROP caused larger reductions in VT compared with blockade of beta 1-receptors only (ATEN), suggesting that beta 2-mediated bronchodilation plays a role in the VT response to heavy exercise. PMID- 2885302 TI - Effects of adrenergic agonists and antagonists on muscle O2 uptake and lactate metabolism. AB - To investigate adrenergic receptor-mediated responses in dog gastrocnemius plantaris muscle, several catecholamine agonists, isoproterenol, epinephrine, norepinephrine, and phenylephrine, and two antagonists, propranolol and phenoxybenzamine, were given during repetitive, isotonic, tetanic contractions. The response variables that were measured were muscle blood flow, shortening during constant load contractions, and arterial and venous O2 and lactate concentrations. The calculated variables were O2 uptake (VO2), net lactic acid output (L), and power output. In the control experiments, the contractions increased VO2 to approximately 50 times rest by 2 min. Thereafter, shortening, work, and VO2 declined together by 17% at 30 min, indicating muscle fatigue. L increased rapidly to nearly 0.8 mumol X g-1 X min-1 by 2 min, declined to 0.3-0.4 mumol X g-1 X min-1 by 7 min, and was like rest at 15, 22.5, and 30 min. The arterial lactate concentration rose steadily from rest to 30 min of contractions. Epinephrine infusion stopped the decline of VO2 during the contractions, but this effect was not observed with the other agonists. Propranolol decreased VO2 compared with controls at 22.5 and 30 min of contractions. Phenoxybenzamine decreased VO2 compared with controls at all times during contraction, and the decline with time was present. Coinfusion of epinephrine with propranolol reduced the decline in VO2 observed with propranolol alone. Both epinephrine and isoproterenol increased L compared with controls. This epinephrine response was antagonized by propranolol but enhanced by phenoxybenzamine. Both isoproterenol and epinephrine infusions increased arterial lactate concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885304 TI - Psychopharmacology of self-injurious behavior in the mentally retarded. PMID- 2885303 TI - Pulmonary vascular injury by polycations in perfused rat lungs. AB - Polycations, such as protamine sulfate and polylysine, have been implicated in the cause of pulmonary edema, but the mechanism is unknown. We studied the vascular effect of protamine in isolated rat lungs perfused with a cell- and plasma-free solution. Protamine (50-1,000 micrograms/ml) increased lung perfusion pressure and caused edema. Blocking the pulmonary vasoconstriction with papaverine (10(-4) M) did not prevent lung edema. In addition, lungs treated with protamine and papaverine showed increased extravascular leakage of 125I-albumin, indicating increased vascular permeability. Histological examination of these lungs showed marked endothelial injury. Functional endothelial damage was further demonstrated by the impairment of the acetylcholine-induced vascular relaxation in protamine-treated vascular rings. Antihistamines and indomethacin failed to block the pulmonary vasoconstriction and increased vascular permeability caused by protamine. In addition, we found that anionic substances, heparin and albumin, blocked the lung injury induced by protamine, whereas other polycations, polylysine and hexadimethrine bromide, caused pulmonary vasoconstriction and increased vascular permeability similar to protamine. We conclude that protamine causes pulmonary endothelial injury and lung edema and suggest that the injury may be charge mediated. PMID- 2885305 TI - Altered translation of the uncC gene coding for the epsilon subunit of the F1F0 ATPase of Escherichia coli. AB - The nucleotide sequence of the previously described uncC424 allele was determined and found to be the same as that of a wild-type uncC gene. However, a G----A change occurred 7 nucleotides upstream from the translation start codon, changing the putative Shine-Dalgarno sequence from GAGG to GAAG. Four revertant strains were examined. In one revertant, which had normal growth and membrane properties, a single base deletion had occurred to re-form the Shine-Dalgarno sequence GAGG 1 nucleotide closer to the translation start codon. A second revertant had a single base deletion in the preceding uncD gene, causing an extension of the beta subunit by 6 amino acids and an increase, presumably by translational coupling, in the amount of epsilon subunit. The third and fourth revertant strains were phenotypically similar and had either C----T or G----T changes 18 or 19 nucleotides, respectively, upstream from the translation start codon. PMID- 2885306 TI - Amino acid concentrations in Rhodospirillum rubrum during expression and switch off of nitrogenase activity. AB - The amino acid concentrations in the phototrophic bacterium Rhodospirillum rubrum were measured during growth under nif-repressing and nif-derepressing conditions. The effects of ammonium, glutamine, darkness, phenazine methosulfate, and the inhibitors methionine sulfoximine and azaserine on amino acid levels of cells were tested. The changes were compared to changes in whole-cell nitrogenase activity and ADP-ribosylation of dinitrogenase reductase. Glutamate was the dominant amino acid under every growth condition. Glutamine levels were equivalent when cells were grown on high-ammonia (nif-repressing) medium or glutamate (nif-derepressing) medium. Thus, glutamine is not the solitary agent that controls nif expression. No other amino acid correlated with nif expression. Glutamine concentrations rose sharply when either glutamate-grown or N-starved cells were treated with ammonia, glutamine, or azaserine. Glutamine levels showed little change upon treatment of the cells with darkness or ammonium plus methionine sulfoximine. Treatment with phenazine methosulfate resulted in a decrease in glutamine concentration. The glutamine concentration varied independently of dinitrogenase reductase ADP-ribosylation, and it is concluded that an increase in glutamine concentration is neither necessary nor sufficient to initiate the modification of dinitrogenase reductase. No other amino acid exhibited changes in concentration that correlated consistently with modification. Glutamine synthetase activity and nitrogenase activity were not coregulated under all conditions, and thus the two regulatory cascades perceive different signal(s) under at least some conditions. PMID- 2885307 TI - Nucleotide sequence and expression of the pyrC gene of Escherichia coli K-12. AB - The pyrC gene of Escherichia coli K-12, which encodes the pyrimidine biosynthetic enzyme dihydroorotase, was cloned as part of a 1.6-kilobase-pair chromosomal fragment. The nucleotide sequence of this fragment was determined. An open reading frame encoding a 348-amino acid polypeptide (Mr = 38,827) was identified as the pyrC structural gene by comparing the amino acid composition predicted from the DNA sequence with that previously determined for the dihydroorotase subunit. The pyrC promoter was mapped by primer extension of in vivo transcripts. Transcriptional initiation was shown to occur within a region located 36 to 39 base pairs upstream of the pyrC structural gene. Pyrimidine availability appears to affect the use of the minor transcriptional initiation sites. The level of pyrC transcription and dihydroorotase synthesis was coordinately derepressed by pyrimidine limitation, indicating that regulation occurs, at least primarily, at the transcriptional level. Inspection of the pyrC nucleotide sequence indicates that gene expression is not regulated by an attenuation control mechanism similar to that described for the pyrBI operon and the pyrE gene. A possible mechanism of transcriptional control involving a common repressor protein is suggested by the identification of a highly conserved, operatorlike sequence in the promoter regions of pyrC and the other pyrimidine genes (i.e., pyrD and carAB) whose expression is negatively regulated by a cytidine nucleotide effector. PMID- 2885308 TI - A traC mutant that retains sensitivity to f1 bacteriophage but lacks F pili. AB - An F lac pro mutant which was temperature sensitive for infection by the filamentous bacteriophage f1 but resistant to the F-specific icosahedral RNA phage f2 was isolated. Cells carrying the F' mutation failed to elaborate F pili at all temperatures. Mutant cells were able to pair with recipient cells during bacterial conjugation, but transfer of conjugal DNA occurred at a greatly reduced frequency. Complementation analyses showed the F' mutation to be in the traC gene. When a plasmid carrying traC was introduced into hosts harboring the F' mutation, phage sensitivity, the ability to elaborate F pili, and conjugation efficiency were restored. The mutation was named traC1044. The F lac pro traC1044 mutant appears to be unique among traC mutants in retaining host sensitivity to the filamentous phage f1 in the absence of expression of extended F pili. Phage f1 attachment sites appeared to be present at the cell surface in traC1044 mutants. The reduced accessibility of these sites may account for the reduced efficiency of phage f1 infection of traC1044 hosts, although the possibility that a defect was present in the receptor site itself was not eliminated. Membranes of hosts carrying the F' mutation contained a full complement of mature F-pilin subunits, so the product of traC is presumably required for pilus assembly but not for pilin processing. This, together with the deficiency in conjugal DNA transfer, suggests that traC may be part of a membrane-spanning tra protein complex responsible for pilus assembly and disassembly and conjugal DNA transmission. PMID- 2885310 TI - Treatment outcome with clozapine in tardive dyskinesia, neuroleptic sensitivity, and treatment-resistant psychosis. AB - Thirty-eight chronically ill psychotic patients were treated with clozapine for indications of tardive dyskinesia, severe extrapyramidal side effects caused by other neuroleptics, or treatment-resistant psychosis. Fifty-five percent of all patients and 40% of schizophrenics improved with clozapine. Abnormal involuntary movements were suppressed during treatment and, with 1 exception, returned to baseline levels after clozapine was discontinued. Our results support the conclusion that clozapine's efficacy in refractory cases and its lack of neurological side effects make it a unique neuroleptic with advantages over conventional antipsychotic agents. The drug appears to be safe when treatment is accompanied by frequent clinical and hematologic monitoring. PMID- 2885309 TI - Mapping of export signals of Pseudomonas aeruginosa pilin with alkaline phosphatase fusions. AB - Pili of Pseudomonas aeruginosa are assembled from monomers of the structural subunit, pilin, after secretion of this protein across the bacterial membrane. These subunits are initally synthesized as precursors (prepilin) with a six-amino acid leader peptide that is cleaved off during or after membrane traversal, followed by methylation of the amino-terminal phenylalanine residue. This report demonstrates that additional sequences from the N terminus of the mature protein are necessary for membrane translocation. Gene fusions were made between amino terminal coding sequences of the cloned pilin gene (pilA) and the structural gene for Escherichia coli alkaline phosphatase (phoA) devoid of a signal sequence. Fusions between at least 45 amino acid residues of the mature pilin and alkaline phosphatase resulted in translocation of the fusion proteins across the cytoplasmic membranes of both P. aeruginosa and E. coli strains carrying recombinant plasmids, as measured by alkaline phosphatase activity and Western blotting. Fusion proteins constructed with the first 10 amino acids of prepilin (including the 6-amino-acid leader peptide) were not secreted, although they were detected in the cytoplasm. Therefore, unlike that of the majority of secreted proteins that are synthesized with transient signal sequences, the membrane traversal of pilin across the bacterial membrane requires the transient six-amino acid leader peptide as well as sequences contained in the N-terminal region of the mature pilin protein. PMID- 2885311 TI - A case of nonneuroleptic malignant syndrome. AB - Neuroleptic malignant syndrome is a diagnosis that has been reported with increasing frequency in recent years. We report the case of a patient who was not treated with a neuroleptic but in whom a syndrome identical to neuroleptic malignant syndrome developed. The case highlights the overuse of and the confusion about the diagnosis of the syndrome. PMID- 2885312 TI - A new extended globoglycolipid carrying the stage specific embryonic antigen-1 (SSEA-1) determinant in mouse kidney. AB - Two neutral glycolipids carrying the stage specific embryonic antigen-1 (SSEA-1) and SSEA-3 determinants, respectively, were purified from mouse kidney by a combination of column chromatographies and droplet counter-current chromatography. The structures of the glycolipids (GL-X and GL-Y) were determined by means of GLC, 1H-NMR spectroscopy, negative-ion fast atom bombardment mass spectrometry, a methylation study, and sequential degradation. GL-X was demonstrated to be galactosyl beta 1-3globotetraosylceramide, the structure of which had already been characterized to be that of SSEA-3 by Kannagi et al. [1983) J. Biol. Chem. 258, 8934-8942). GL-Y was a new glycolipid containing fucose, galactose, glucose, N-acetylgalactosamine, and N-acetylglucosamine in a molar ratio of 1:4:1:1:1. The methylation study results indicated that it contained 3 mol of terminal sugars composed of 2 mol of galactose and 1 mol of fucose with two branching points at N-acetylgalactosamine and N acetylglucosamine. From the data obtained by 1H-NMR spectroscopy, mass spectrometry, and a binding assay using an anti-SSEA-1 monoclonal antibody (PM81) cloned by Ball et al. [1983) J. Immunol. 130, 2937-2941), we propose the structure of GL-Y to be Gal beta 1-4GlcNAc beta 1-6GalNAc beta 1-3Gal alpha 1 4Gal beta 1-4Glc beta 1-ceramide. (sequence; see text) Fuc alpha 1 Gal beta 1 This is the first report on the isolation and characterization of a glycolipid carrying the SSEA-1 determinant on its globo-core structure. PMID- 2885313 TI - Genetic control of the expression of two extended globoglycolipids carrying either the stage specific embryonic antigen-1 or -3 determinant in mouse kidney. AB - In the preceding paper (J. Biochem. 101, 553-562 (1987], we reported the structures of two neutral glycolipids (GL-X and GL-Y) purified from mouse kidney, and demonstrated the occurrence of polymorphic variation of these two glycolipids in inbred strains of mice. GL-X was characterized as galactosyl beta 1 3globotetraosylceramide, which was reported to be stage specific embryonic antigen-3 (SSEA-3) by Kannagi et al. (J. Biol. Chem. 258, 8934-8942 (1983], and GL-Y as 3-fucolactosaminyl beta 1-6(galactosyl beta 1-3)globotetraosylceramide, which carries the SSEA-1 determinant. In order to elucidate the mode of genetic control of GL-X and GL-Y expression, two variants, i.e., BALB/c mice expressing GL-Y and DBA/2 mice lacking GL-Y but expressing GL-X as the major neutral glycolipid, were subjected to mating experiments and glycolipid analysis. F1 hybrids expressed GL-Y, therefore GL-Y expression is dominant, and DBA/2 mice were determined to be recessive homozygotes. Through analysis of backcross and F2 mice, DBA/2 mice were demonstrated to carry a single defective autosomal gene, and it is concluded that because of this DBA/2 mice cannot express GL-Y and so accumulate GL-X. An attempt to map the gene controlling GL-Y expression on mouse chromosomes using coat colors and recombinant inbred strains was not successful. PMID- 2885314 TI - 13C-NMR studies of porcine kidney D-amino acid oxidase reconstituted with 13C enriched flavin adenine dinucleotide. Effects of competitive inhibitors. AB - D-Amino acid oxidase (DAO) from porcine kidney was reconstituted with FAD's which were enriched with 13C at the 2-, 4-, 4a-, and 10a-positions of the isoalloxazine moiety, and 13C-NMR spectra of the reconstituted DAO were measured in the absence and presence of various competitive inhibitors. When compared to the corresponding chemical shifts of FMN at infinite dilution (Moonen, C.T.W. et al. (1984) Biochemistry 23, 4859-4867), the resonances of C(2), C(4), C(4a), and C(10a) of FAD bound to apoDAO were all shifted to higher field. However, when the reconstituted DAO was complexed with o-, m-, p-aminobenzoate, or benzoate, each of the four 13C-signals underwent a different change in chemical shift. In these changes we observed no characteristics which distinguish DAO-aminobenzoate complexes from DAO-benzoate complex, even though o-, m-, and p-aminobenzoates are known to form charge-transfer complexes with DAO. The signals due to 2- and 4-13C were more sensitive to the formation of the inhibitor-DAO complexes than those of the other carbon atoms. These findings suggest the modulation of the hydrogen bonds at the oxygen atoms of C(2) = O and C(4) = O with the protein moiety as the result of the inhibitor-binding. PMID- 2885315 TI - In vivo detection of regulatory factor binding sites in the 5' flanking region of maize Adh1. AB - In vivo dimethyl sulfate footprinting experiments have been used to locate the binding sites of regulatory molecules in the TATA proximal portion of the maize alcohol dehydrogenase-1 gene. In several tissues and organs, Adh1 is transcriptionally induced by anaerobic stress, and the various alleles of Adh1 can show a quantitative differential response to induction. Two regulatory molecules were found to be bound to the promoter only when the gene was induced. The binding sites for these factors mapped to regions located at -100 to -108 and -186 to -190 relative to the site of transcript initiation. Two additional regulatory molecules were bound to sites located at positions -117 to -120 and 138 to -145 regardless of the state of transcription. However, the factor bound at the -138 to -145 region was found to alter its binding characteristics when the gene was induced. PMID- 2885316 TI - Directed mutagenesis of the beta-subunit of F1-ATPase from Escherichia coli. AB - Oligonucleotide-directed mutagenesis was used to generate six mutant strains of Escherichia coli which had the following specific amino acid substitutions in the beta-subunit of F1-ATPase: (i) Lys-155----Gln; (ii) Lys-155----Glu; (iii) Gly-149 ---Ile; (iv) Gly-154----Ile; (v) Tyr-297----Phe;(vi) Tyr-354----Phe. The effects of each mutation on growth of cells on succinate plates or limiting (3 mM) glucose and on cell membrane ATPase activity and ATP-driven pH gradient formation were studied. The results showed Lys-155 to be essential for catalysis, as has been predicted previously from sequence homology and structural considerations; however, the results appear to contradict the hypothesis that Lys-155 interacts with one of the substrate phosphate groups because the Lys-155----Glu mutation was less detrimental than Lys-155----Gln. Gly-149 and Gly-154 have been predicted to be involved in essential conformational changes in F1-ATPase by virtue of their position in a putative glycine-rich flexible loop structure. The mutation of Gly-154----Ile caused strong impairment of catalysis, but the Gly-149----Ile mutation produced only moderate impairment. The two tyrosine residues chosen for mutation were residues which have previously received much attention due to their being the sites of reaction of the inactivating chemical modification reagents 4 chloro-7-nitrobenzofurazan (Tyr-297) and p-fluorosulfonylbenzoyl-5'-adenosine (Tyr-354). We found that mutation of Tyr-297----Phe caused only minor impairment of catalysis, and mutation of Tyr-354----Phe produced no impairment. Therefore, a direct role for either of these tyrosine residues in catalysis is unlikely. PMID- 2885317 TI - Alpha-proton abstraction and carbanion formation in the mechanism of action of lysyl oxidase. AB - Tetranitromethane (TNM) was employed as an electrophilic reagent to probe for the lysyl oxidase-catalyzed processing of n-butylamine to an intermediate carbanion during the oxidation of this amine to n-butyraldehyde according to a prior description of the use of TNM to trap enzyme-generated carbanion intermediates (Christen, P. and Riordan, J. F. (1968) Biochemistry 7, 1531-1538). The addition of n-butylamine to assay mixtures containing lysyl oxidase and TNM markedly increased the background rate of nitroform release. The Km for n-butylamine was essentially the same whether determined from the rate of lysyl oxidase-catalyzed nitroform release or from the rate of n-butyraldehyde production in the absence of TNM, the latter assessed by measurements of the rate of H2O2 formation. The initial rate of substrate- and enzyme-dependent nitroform production was linearly related to functional active site content. These data are consistent with the enzyme-dependent abstraction of an alpha-proton from the substrate to form an intermediate enzyme-bound carbanion. Kinetic analyses of the oxidation of n butylamine and 1,1-dideutero-n-butylamine by lysyl oxidase revealed kinetic isotope effects on Vmax and Vmax/Km parameters, consistent with a rate contributing alpha-proton abstraction step. These and other available data are incorporated into a proposal for the mechanism of action of this enzyme. PMID- 2885318 TI - Correlation between the ATP synthetic active state and the ATP hydrolytic active state in chloroplast ATP synthase-ATPase complex CF0 . CF1. AB - Illumination of chloroplast thylakoids activates ATP synthase-ATPase complex CF0 . CF1. The time course of ATP synthesis is linear if ADP and Pi are added before or simultaneously with illumination. ATP synthesis initiated by adding the substrates in the light exhibits a curvilinear time course with a low initial rate (Vi). Vi, but not the rate at a steady state, decreases with increasing preillumination time with a half-time of 2 s. Coincident with this decrease in Vi, activation of ATP hydrolysis takes place. In the postillumination dark, restoration of Vi is observed: Vi increases with increasing time intervals between the end of illumination and the addition of the substrates with simultaneous reillumination (half-time of 3 s). Coincident with this restoration of Vi, inactivation of ATP hydrolysis takes place. Such an increase in Vi in the postillumination dark is not observed in thylakoids pretreated with N ethylmaleimide. These results suggest the following: in the light, the ATP synthetically active, but ATP hydrolytically inactive state (Es) converts to the ATP hydrolytically active, but ATP synthetically inactive (or less active) state (Eh) in the absence of ADP and Pi. The N-ethylmaleimide pretreatment inhibits this process. In the postillumination dark, the reverse conversion takes place. PMID- 2885319 TI - F1F0-ATPase from Escherichia coli with mutant F0 subunits. Partial purification and immunoprecipitation of F1F0 complexes. AB - Previously identified mutations in subunits a and b of the F0 sector of the F1F0 ATPase from Escherichia coli are further characterized by isolating detergent solubilized, partially purified F1F0 complexes from cells bearing these mutations. The composition of the various F1F0 complexes was judged by quantitating the amount of each subunit present in the detergent-solubilized preparations. The composition of the F0 sectors containing altered polypeptides was determined by quantitating the F0 subunits that were immunoprecipitated by antibodies directed against the F1 portion. In this way, the relative amounts of F0 subunits (a, b, c) which survived the isolation procedure bound to F1 were determined for each mutation. This analysis indicates that both missense mutations in subunit a (aser206----leu and ahis245----tyr) resulted in the isolation of F1F0 complexes with normal subunit composition. The nonsense mutation in subunit a (atyr235----end) resulted in isolation of a complex containing the b and c subunits. The bgly131----asp mutation in the b subunit results in an F0 complex which does not assemble or survive the isolation. The isolated F1F0 complex containing the mutation bgly9----asp in the b subunit was defective in two regards: first, a reduction in F1 content relative to F0 and second, the absence of the a subunit. Immunoprecipitations of this preparation demonstrated that F1 interacts with both c and mutant b subunits. A strain carrying the mutation, bgly9----asp, and the compensating suppressor mutation apro240----leu (previously shown to be partially unc+) yielded an F1F0 ++ complex that remained partially defective in F1 binding to F0 but normal in the subunit composition of the F0 sector. The assembly, structure, and function of the F1F0 ATPase is discussed. PMID- 2885320 TI - Proliferating cell nuclear antigen/cyclin is an interleukin 2-responsive gene. AB - Previously, we have shown that a protein designated p36 is synthesized at a high rate during interleukin 2-driven proliferation of a cloned T lymphocyte, L2. Biosynthesis of p36 increases 1000-fold during the initial mid-G1 phase of the cell cycle and remains high while the cells proliferate. In this report, we show that p36 has the same migration pattern by two-dimensional gel electrophoresis as proliferating cell nuclear antigen (PCNA)/cyclin and that antiserum to PCNA/cyclin selectively immunoprecipitates p36. In addition, by indirect immunofluorescence, PCNA/cyclin accumulates in the nucleus of interleukin 2 stimulated L2 cells during proliferation and is not detectable prior to the initial S phase or after proliferation ceases. These data indicate that PCNA/cyclin expression is induced by interleukin 2 and that PCNA/cyclin accumulation is closely associated with T lymphocyte proliferation. PMID- 2885321 TI - Divergent stimulatory and inhibitory actions of carbamoylcholine on gastric D cells. AB - Carbamoylcholine (carbachol) has been shown to inhibit somatostatin release from gastric D-cells. We observed that this dose-dependent inhibitory effect was accompanied by decreases in cellular cyclic adenosine 3':5'-monophosphate (cAMP) production and increases in parameters of membrane inositol phospholipid turnover. However, after pretreatment of D-cells with pertussis toxin (200 ng/ml), carbachol paradoxically stimulated basal somatostatin release and potentiated the secretagogue action of forskolin. Pertussis toxin pretreatment blocked the ability of carbachol to decrease cAMP production but changes in inositol phospholipid turnover were unaffected. Atropine reversed all of the observed changes induced by carbachol. These data suggest that muscarinic cholinergic receptors mediate both stimulatory and inhibitory regulation of D cells. The inhibitory effect may involve pertussis toxin-sensitive inhibitory guanine nucleotide binding proteins while the stimulatory effect may result from the consequences of membrane phosphoinositide turnover. PMID- 2885322 TI - Cascade control of Escherichia coli glutamine synthetase. Purification and properties of PII protein and nucleotide sequence of its structural gene. AB - A procedure was developed to purify large quantities of PII protein from an Escherichia coli strain which contains a multicopy plasmid harboring the structural gene of PII (the glnB gene). Ultraviolet spectra of uridylylated and unuridylylated PII were obtained using the purified PII and empirical formulas to calculate the concentration of protein and the average number of uridylylated subunits per molecule were derived. A continuous fluorometric assay for the measurement of uridylylated PII (PIID) and adenylyltransferase (ATase) was also established. Rate measurements at various concentrations of PIID and at a fixed concentration of ATase showed that a tetrameric PIID molecule interacts with only one ATase molecule at a time. The complete nucleotide sequence of the glnB gene was determined and parts of the deduced amino acid sequence were confirmed by the results of amino acid sequence analysis of peptides. The PII subunit consists of 103 amino acids (Mr = 11,580). Two tyrosines reside at positions 46 and 51, where Tyr51 is the site of uridylylation. Nucleotide sequence analysis of the upstream region showed no obvious sites for the binding of RNA polymerase, indicating that the glnB gene is a part of an as yet unidentified operon. PMID- 2885323 TI - Active site of Pseudomonas aeruginosa exotoxin A. Glutamic acid 553 is photolabeled by NAD and shows functional homology with glutamic acid 148 of diphtheria toxin. AB - Photoaffinity labeling with native NAD, a method employed earlier with diphtheria toxin (DT), was used to identify an active site residue of Pseudomonas aeruginosa exotoxin A (ETA). An enzymically active fragment (Mr 27,000), derived by partial digestion of ETA with thermolysin, was irradiated with ultraviolet light (254 nm) in the presence of various radiolabeled preparations of NAD. Label from the nicotinamide moiety was efficiently transferred to the protein (maximally 0.79 mol/mol), and the label was exclusively located at position 553. This position, like that photolabeled in DT (position 148), corresponds to glutamic acid in the native protein. Chromatographically identical photo-products were generated at these positions in the two toxins. Glu-553 lies in a cleft in domain III that is believed to represent the active site of ETA, and other evidence supports the notion that Glu-553 of ETA and Glu-148 of DT are directly involved in catalysis. When Glu-553 of ETA was aligned with Glu-148 of DT, we found similarities of local primary structure not detected earlier. These results suggest that the catalytically active domains of ETA and DT may be evolutionarily related, and they provide information that should prove useful for preparing vaccines against ETA by recombinant DNA methods. PMID- 2885324 TI - A unique AT-rich hypervariable minisatellite 3' to the ApoB gene defines a high information restriction fragment length polymorphism. AB - A DNA restriction fragment length polymorphism has been found immediately 3' to the human apoB gene. Digestion of many different human DNAs at sites flanking the region and Southern blotting analysis reveal that this region can vary in length by approximately 300 base pairs with five alleles readily distinguishable. The length polymorphism is due to a unique AT-rich minisatellite that consists primarily of a 30-base pair tandem repeat with two structurally related subunit sequences, x (ATAATTAAATATTTT) and y (ATAATTAAAATATTT). In general, the sequences repeat in an x-y order. The AT-rich region also contains variant x and y sequences that result from C or G for A substitution. Sequence analysis of one large allele revealed the expected increased number of xy repeats. In addition, similar analysis of three different smaller alleles with the same apparent size on Southern blotting analysis showed that all were of slightly different size due to minor differences in the number of xy repeats. The heterogeneity of this AT rich minisatellite provides the basis for a highly informative restriction fragment length polymorphism of the apoB gene and should be very useful in association and linkage analysis studies of the contribution of this locus to atherosclerosis susceptibility. PMID- 2885325 TI - The defective proton-ATPase of uncA mutants of Escherichia coli. Identification by DNA sequencing of residues in the alpha-subunit which are essential for catalysis or normal assembly. AB - A group of mutant uncA alleles, affecting essential residues of the alpha-subunit of Escherichia coli proton-ATPase, have been identified by intragenic complementation mapping, cloning, and DNA sequencing. One of the mutations, uncA450, abolishes normal assembly of F1-ATPase. The amino acid substitution found was Glu-299----Lys, which is predicted to lie in an alpha-helix in alpha subunit. The reversal of the charge at residue 299 is a likely cause of defective assembly. The uncA462 allele causes impairment of catalysis while allowing normal assembly of membrane-bound F1-ATPase. The amino acid substitution found was Ser 347----Phe. Three mutations which impair catalysis but do not cause structural perturbation of either membrane-bound or solubilized F1ATPase were characterized as follows: uncA401, Ser-373----Phe; uncA447, Gly-351----Asp; uncA453, Ser-375--- Phe. We predict here that the nucleotide-binding domain of alpha-subunit is formed by the amino acids in the sequence from residue 160 to approximately residue 340. The mutations which cause impairment of catalysis lie in a short segment between residues 347-375 of alpha-subunit, at the C-terminal end of the predicted nucleotide-binding domain. This segment is suggested to be important for beta-alpha-beta intersubunit conformational interaction involved in positive catalytic cooperativity in F1-ATPase. PMID- 2885326 TI - Stereospecific labilization of the C-4' pro-S hydrogen of pyridoxamine 5' phosphate in aspartate aminotransferase. Activators and inhibitors. AB - Measurement of the stereospecific release of the pro-S proton from C-4' of enzyme bound pyridoxamine 5'-phosphate provides an experimental means to probe parts of the active site of aspartate aminotransferase independently of substrate turnover (Tobler, H. P., Christen, P., and Gehring, H. (1986) J. Biol. Chem. 261, 7105 7108). The release of pro-S 3H from enzyme-bound [3H]pyridoxamine 5'-phosphate is 30,000 times faster than from free coenzyme. Enzyme-bound [3H]pyridoxine 5' phosphate is not detritiated suggesting an essential role of the 4'-amino group. Formation of the unproductive complex of the [3H]pyridoxamine 5'-phosphate-enzyme with aspartate or glutamate results in a 400-fold acceleration of 3H release. In contrast, addition of borohydride or cyanoborohydride immediately stops 3H release. Experiments with a fluorescent reporter group and with differential chemical modifications indicate that the activating effect of aspartate on the release of 3H is accompanied by a shift of the so-called open/closed conformational equilibrium of the enzyme (Kirsch, J.F., Eichele, G., Ford, G. C., Vincent, M.G., Jansonius, J.N., Gehring, H., and Christen, P. (1984) J. Mol. Biol. 174, 497-525) toward the closed conformation; the inhibiting effect of borohydride and cyanoborohydride appears to be accompanied by a shift toward the open conformation. Apparently, at least part of the catalytic apparatus of aspartate aminotransferase becomes fully operative only in the closed conformation of the enzyme. PMID- 2885328 TI - Enzymes that process somatostatin precursors. A novel endoprotease that cleaves before the arginine-lysine doublet is involved in somatostatin-28 convertase activity of rat brain cortex. AB - The selective processing activity which generates both the NH2- and COOH-terminal fragments of the octacosapeptide somatostatin-28 (S-28) was investigated. Separation into two distinct proteolytic activities was achieved by ion-exchange chromatography. An endoprotease cleaving either the substrate Pro-Arg-Glu-Arg-Lys Ala-Gly-Ala-Lys-Asn-Tyr-NH2, i.e. [Ala17,Tyr20]S-28-(10-20)-NH2 (peptide I), or the octacosapeptide somatostatin-28, on the NH2 side of the Arg-Lys doublet was separated from an aminopeptidase B-like activity. Whereas the endoprotease cleaves a single peptide bond, between Glu12 and Arg13 of S-28, the aminopeptidase B-like enzyme removes both Arg13 and Lys14 stepwise from the NH2 terminus of the corresponding COOH-terminal fragment. This endoprotease activity peaks around pH 8.5, whereas the optimal aminopeptidase B-like activity is in the pH range 6.2-8.5. Combination of both enzymes resulted in the recovery of the overall S-28 convertase activity with an optimal pH at 7. In addition, this endoprotease appears to be very sensitive to divalent cations since it is strongly inhibited by chelating agents. The use of selectively modified undecapeptides derived from the reference substrate peptide I by a single modification of the amino acids Glu12, Arg13, and Lys14 at the cleavage locus showed that both basic residues are critically important, whereas Glu12 is not. It is proposed that S-28 processing involves a divalent cation-sensitive endoprotease that is sensitive to thiol reagents, which cleaves before the Arg Lys doublet, which is not trypsin-like, and whose action is coupled to an aminopeptidase B-like enzyme. PMID- 2885327 TI - The purified ATPase from chromaffin granule membranes is an anion-dependent proton pump. AB - The proton-ATPase of chromaffin granules was purified so as to maintain its proton-pumping activity when reconstituted into phospholipid vesicles. The purification procedure involved solubilization with polyoxyethylene 9 lauryl ether, hydroxylapatite column, precipitation by ammonium sulfate, and glycerol gradient centrifugation. The protease inhibitor mixture used in previous studies inhibited the proton-pumping activity of the enzyme; therefore, the protein was stabilized by pepstatin A and leupeptin. The enzyme was purified at least 50-fold with respect to both ATPase and proton-pumping activity. The ATP-dependent proton uptake activity of the reconstituted enzyme was absolutely dependent on the presence of Cl- or Br- outside the vesicles, whereas sulfate, acetate, formate, nitrate, and thiocyanate were inhibitory. Sulfate inhibition seems to be due to competition with Cl- on the anion-binding site outside the vesicles, whereas nitrate and thiocyanate inhibited only from the internal side. As with the inhibition by N-ethylmaleimide, the proton-pumping activity was much more sensitive to nitrate than the ATPase activity. About 20 mM nitrate were sufficient for 90% inhibition of the proton-pumping activity while 100 mM inhibited only 50% of the ATPase activity both in situ and in the reconstituted enzyme. The possible regulatory effect of anions on the ATP-dependent proton uptake in secretory granules is discussed. PMID- 2885329 TI - Thermolabile proton translocating ATPase and pump activities in a clathrin-coated vesicle fraction from an acidification defective Chinese hamster cell line. AB - We have recently described a mutant of Chinese hamster ovary cells, termed G.7.1, that contains a temperature-sensitive, conditionally lethal mutation resulting in defective vacuolar acidification (Marnell, M. H., Mathis, L. S., Stookey, M., Shia, S.-P., Stone, D.K., and Draper, R. K. (1984) J. Cell Biol. 99, 1907-1916). To further characterize the lesion, clathrin-coated vesicles were partially purified from wild type and G.7.1 cells, and the thermolabilities of vanadate and oligomycin-insensitive, N-ethylmaleimide-sensitive, H+-ATPase activity, 32Pi ATPase exchange activity, and proton pumping were compared. All three parameters of H+ pump activity were markedly diminished by preincubation at 44 degrees C for vesicles harvested from the G.7.1 cells, but not for those from wild type cells. Phosphatidylserine did not protect against heat inactivation in vesicle fractions prepared from G.7.1 cells. The results suggest that the mutation responsible for defective acidification in G.7.1 cells is expressed at the level of the proton pump of organelles present in our clathrin-coated vesicle-enriched preparation. PMID- 2885330 TI - The care of burns from methyl bromide (case report). PMID- 2885331 TI - Abdominal aortic occlusion following electric injury. PMID- 2885332 TI - Differential control of mRNA levels for Thy-1 antigen and laminin in rat mammary epithelial and myoepithelial-like cells. AB - Thy-1 antigen and laminin are two components often associated with the basement membrane of the rat mammary gland and are thought to be synthesized, at least in part, by the adjacent myoepithelial cells in vivo. The relative levels of Thy-1 mRNA and laminin mRNA are compared in a rat mammary cuboidal epithelial cell line and a derivative elongated myoepithelial-like cell line by hybridizing cloned cDNAs to cellular mRNA isolated from these cell types. Although the elongated myoepithelial-like cells synthesize four times as much laminin protein as the cuboidal epithelial cells, there is only a 1.7-fold increase in laminin mRNA between the two cell types. In contrast the 17-fold increase in Thy-1 antigen between the elongated cells and the cuboidal cells can be accounted for completely by a 14-18-fold increase in Thy-1 mRNA, suggesting that changes in the steady-state levels of Thy-1 mRNA in these cell lines are modulated at either a transcriptional or a post-transcriptional level. Run-off transcription by nuclei isolated from the cell lines does not distinguish between these two possibilities. The comparative results on Thy-1 antigen and laminin show that the enhanced production of two proteins often associated with the basement membrane of the rat mammary gland can be controlled at different levels in the elongated myoepithelial-like cells. PMID- 2885334 TI - Capillary gas chromatographic-mass spectrometric study of the effect of solvents on metoprolol and other aryloxypropanolamines. AB - When metoprolol in methanol was analysed by capillary gas chromatography (GC), an additional peak was observed; mass spectrometry (MS) showed this additional peak to have a molecular weight 12 dalton higher than that of the parent compound. A similar phenomenon was observed with other beta-adrenergic blocking aryloxypropanolamines in methanol or dichloromethane. Capillary GC-MS using deuterated solvents as isotopic markers showed that a methylene group from the solvents was incorporated into the parent molecule. The structure of the observed products and the mechanism of their formation are proposed. PMID- 2885333 TI - Determination of carazolol in tissues of pigs by high-performance liquid chromatography. AB - A new and sensitive method is described for the determination of the beta receptor blocker Carazolol, 4-(2-hydroxy-3-isopropylaminopropoxy)-carbazole, in different animal tissues. The procedure comprises extraction of Carazolol from tissue, clean-up by Kieselgel adsorption and high-performance liquid chromatographic separation with fluorimetric detection. The determination limit is 0.48 microgram/kg sample. The method has been verified by measuring Carazolol in liver, kidney and filet of a fattening pig treated with Carazolol before slaughtering. PMID- 2885335 TI - Determination of tulobuterol in human plasma by capillary gas chromatography. PMID- 2885336 TI - Serial changes in thyroid-stimulating antibody and thyrotropin binding inhibitor immunoglobulin at the time of postpartum occurrence of thyrotoxicosis in Graves' disease. AB - Thyroid-stimulating antibody (TSAb) and TSH binding inhibitor immunoglobulin (TBII) were measured serially in 10 patients with Graves' disease at the time of postpartum onset (n = 2) or relapse (n = 8) of Graves' thyrotoxicosis and in 5 patients with Graves' disease who were in remission and had no postpartum relapse of Graves' thyrotoxicosis. TSAb was measured by a sensitive cAMP accumulation assay using FRTL-5 cells, and TBII was determined by radioreceptor assay. In no patient with either recurrent or new onset postpartum hyperthyroidism did the serum free T3 index (FT3I) rise before the free T4 index (FT4I). Of the 10 patients who had postpartum thyrotoxicosis, concomitant increases in serum FT4I and FT3I, and TSAb and TBII were observed in only 1 patient. Increases in TSAb and TBII after those in FT4I and FT3I occurred in 6 patients. In 1 patient, an increase in TBII was associated with the occurrence of thyrotoxicosis, but TSAb increased 1 month later. In the other 2 patients, a TSAb increase was followed by the development of thyrotoxicosis, but TBII increased later. In 3 of these 10 patients, the increased serum FT4I and FT3I values decreased spontaneously, whereas the TSAb and TBII levels increased continuously. No positive test or increase in TSAb or TBII was found in the 5 patients with Graves' disease who did not have a postpartum relapse of thyrotoxicosis. These data indicate that postpartum initiation of Graves' thyrotoxicosis is not always associated with an increase in circulating anti-TSH receptor antibodies and that such parameters are poor indicators of thyroid function. Intrathyroidal humoral or cell-mediated immunological mechanisms may also be involved in mediating thyrotoxicosis in Graves' disease. PMID- 2885337 TI - Somatostatin does not alter insulin-mediated glucose disposal. AB - We examined the effect of somatostatin (SRIH) infusion on insulin-mediated glucose disposal (Rd) in normal young subjects (n = 8) to determine the influence of SRIH on insulin action. Paired 3-h euglycemic insulin clamp studies were performed in random order employing insulin alone (25 mU/m2 X min) or insulin with SRIH (250 micrograms/h) and replacement of basal glucagon (0.4 ng/kg X min). Basal plasma glucose, insulin, glucagon (IRG), and GH concentrations, hepatic glucose production, and Rd were similar on each occasion. Steady state (10-180 min) plasma insulin insulin alone, 283 +/- 10 (+/- SEM); insulin, IRG, and SRIH, 284 +/- 10 pmol/L) and glucagon levels (insulin alone, 84 +/- 7; insulin, IRG, and SRIH, 82 +/- 7 ng/L) were similar. Hepatic glucose production (insulin alone, 0.66 +/- 0.12; insulin, IRG, and SRIH, 0.78 +/- 0.48 mg/kg X min) and Rd (insulin alone, 8.16 +/- 0.62; insulin, IRG, and SRIH, 8.17 +/- 0.61 mg/kg X min) were not different at steady state. We conclude that SRIH infusion with glucagon replacement does not augment insulin-mediated glucose disposal in normal young subjects at physiological insulin levels. PMID- 2885338 TI - Multiplicity of serogroups and adhesins in enteropathogenic and enterotoxigenic Escherichia coli isolated from acute diarrhea in Senegal. AB - Escherichia coli strains were isolated from 228 children with diarrhea in Senegal from 1982 to 1984. Among these E. coli involved in cases of diarrhea, we found that 20.3% were enteropathogenic E. coli. Only 3.9% of the strains adhered to the brush borders of human intestinal enterocytes, and they belonged to different serotypes. All these adhesion-positive strains possessed genes encoding for the heat-stable enterotoxin, but their adhesive factors were different regarding serology with anti-colonization factor sera, hemagglutination patterns, electron microscopy structures, or major surface protein subunits. PMID- 2885339 TI - Comparison of throat and nasopharyngeal swab specimens for culture diagnosis of Bordetella pertussis infection. AB - During a 9-month period, we evaluated the relative sensitivity of throat and nasopharyngeal swab cultures for isolation of Bordetella pertussis. Of 38 pertussis cases, 36 (95%) had positive nasopharyngeal cultures, while only 16 of 36 (44%) had positive throat cultures. There were no cases of nasopharyngeal negative, throat-positive cultures. The sensitivity of the direct fluorescent antibody test was 70% when compared with culture. PMID- 2885340 TI - Detection of specific serum immunoglobulin M in nephropathia epidemica (Scandinavian epidemic nephropathy) by a biotin-avidin-amplified immunofluorescence method. AB - A biotin-avidin-amplified indirect immunofluorescence method was used to demonstrate specific serum immunoglobulin M (IgM) antibodies in nephropathia epidemica, the Scandinavian type of hemorrhagic fever with renal syndrome. The antigen in the test was the cross-reacting agent of Korean hemorrhagic fever, Hantaan virus. Sixty-two serum samples from 15 patients with clinically typical nephropathia epidemica were analyzed. Eleven patients had specific IgM in one or more serum samples. The IgM could be demonstrated from day 2 up to day 37, and all patients had detectable specific IgM within 15 days after the onset of disease. In 49 control serum samples, no specific IgM could be detected, indicating a high specificity for the method. The findings demonstrate that the biotin-avidin-amplified immunofluorescence IgM assay is a useful tool in the diagnosis of early nephropathia epidemica disease. PMID- 2885341 TI - Evaluation of anaerobic microdilution MIC results with the Prompt Inoculation System. AB - The Prompt Inoculation System (3M Co.) was compared with the overnight suspension inoculation procedure used with a broth microdilution anaerobic commercial system (Micro-Media Systems) for differences in MIC. MIC results from both suspension methods using six National Committee for Clinical Laboratory Standards recommended quality control organisms were identical in 18 instances (75%) and within +/- 1 log2 dilution in 96% of the comparisons. Results with 45 anaerobic clinical isolates also compared satisfactorily; 83% of the results were identical and 97% were within +/- 1 log2 dilution. In addition, the direct (Prompt) inoculated microdilution trays produced better growth and more valid MIC results; 92% of the clinical isolates produced MIC results versus 79% by the overnight suspension procedure. PMID- 2885342 TI - Economic comparison of enzyme immunoassay and virus isolation procedures for surveillance of arboviruses in mosquito populations. AB - Cost-effectiveness analysis of an enzyme immunoassay (EIA) for the surveillance of arboviruses was conducted. The EIA was compared with conventional virus isolation and serologic identification procedures (virus isolation procedures; VIP). Under most circumstances, EIA was more cost-effective than VIP. Costs for processing mosquito pools by VIP increased with the number of viruses included in the surveillance program and with the prevalence rate of each virus. In contrast to VIP, the prevalence rate did not affect costs for processing pools by EIA. In general, EIA was the most cost-effective procedure, followed by cell culture and mouse bioassays. In a 5-year cost-effectiveness analysis of a model surveillance program in which EIA and cell culture bioassays were used, the EIA again proved to be the most cost-effective assay procedure under most circumstances. PMID- 2885344 TI - A comparison of buspirone, diazepam, and placebo in patients with chronic anxiety states. AB - Buspirone is an antianxiety compound that has been extensively evaluated in clinical trials: it has proved superior to placebo and comparable to diazepam in the treatment of patients with generalized anxiety disorder. In this study, 33 outpatients with generalized anxiety disorder were entered into a crossover study of 3 weeks each of placebo, buspirone 10 to 30 mg daily, and diazepam 10 to 30 mg daily. Psychiatrist and patient ratings were made, together with psychological tests and EEG and skin conductance measures before and after each treatment. Of the nine dropouts, six were on buspirone at the time of dropout. For the remaining 24 patients, the mean daily doses attained of buspirone and diazepam were both 20 mg. On most clinical ratings diazepam was superior to buspirone and placebo, which did not differ. Diazepam produced minor psychomotor changes and the expected major effects on the EEG. Buspirone was without effect. Side effects on buspirone were mainly nausea and giddiness and on diazepam, drowsiness. The lack of efficacy of buspirone is discussed in terms of the previous benzodiazepine exposure--23/24 patients had had previous exposure and only 10 were able to tolerate a pretrial placebo washout period. The implications are considerable for the introduction of any new antianxiety agent not cross-tolerant with the benzodiazepines into a chronically anxious group of patients with previous long-term benzodiazepine therapy. PMID- 2885343 TI - Effect of chronic ethanol feeding on rat hepatocytic glutathione. Compartmentation, efflux, and response to incubation with ethanol. AB - Hepatocytes from rats that were fed ethanol chronically for 6-8 wk were found to have a modest decrease in cytosolic GSH (24%) and a marked decrease in mitochondrial GSH (65%) as compared with pair-fed controls. Incubation of hepatocytes from ethanol-fed rats for 4 h in modified Fisher's medium revealed a greater absolute and fractional GSH efflux rate than controls with maintenance of constant cellular GSH, indicating increased net GSH synthesis. Inhibition of gamma-glutamyltransferase had no effect on these results, which indicates that no degradation of GSH had occurred during these studies. Enhanced fractional efflux was also noted in the perfused livers from ethanol-fed rats. Incubation of hepatocytes in medium containing up to 50 mM ethanol had no effect on cellular GSH, accumulation of GSH in the medium, or cell viability. Thus, chronic ethanol feeding causes a modest fall in cytosolic and a marked fall in mitochondrial GSH. Fractional GSH efflux and therefore synthesis are increased under basal conditions by chronic ethanol feeding, whereas the cellular concentration of GSH drops to a lower steady state level. Incubation of hepatocytes with ethanol indicates that it has no direct, acute effect on hepatic GSH homeostasis. PMID- 2885345 TI - Early phase II clinical trial of remoxipride in treatment of schizophrenia with measurements of prolactin and neuroleptic activity. AB - Twenty hospitalized schizophrenic patients on haloperidol (doses 6 to 80 mg/day; median, 30 mg/day) underwent 4 days of placebo washout before being treated for 6 weeks with remoxipride, a new benzamide derivative with selective D2-dopamine receptor blocking properties. All patients completed the clinical trial period with week 6 doses ranging from 75 to 500 mg/day (median, 225 mg/day). Comparison of final scores with end of placebo washout showed improvement in schizophrenic symptoms in 10 patients and a reduction in the mean score for Clinical Global Impression of severity of illness (14.1%) and Brief Psychiatric Rating Scale total score (23.0%). Remoxipride caused less parkinsonism than the prior neuroleptic therapy and appeared to have little masking effect on tardive dyskinesia. Only slight evidence of serum neuroleptic activity was shown by radio receptor assay measurements using [3H]spiperone binding and calf caudates, and the drug's effect on prolactin elevation was short-lasting (less than 10 hours). The mean elimination half-life of remoxipride was 5.9 hours. These results add to the consistent impression that D2 receptor blockade predicts clinical antipsychotic effects. PMID- 2885346 TI - Nifedipine in neuroleptic-refractory schizophrenia. PMID- 2885347 TI - Pedunculopontine tegmental nucleus of the rat: cytoarchitecture, cytochemistry, and some extrapyramidal connections of the mesopontine tegmentum. AB - The pedunculopontine tegmental nucleus (PPTn) was originally defined on cytoarchitectonic grounds in humans. We have employed cytoarchitectonic, cytochemical, and connectional criteria to define a homologous cell group in the rat. A detailed cytoarchitectonic delineation of the mesopontine tegmentum, including the PPTn, was performed employing tissue stained for Nissl substance. Choline acetyltransferase (ChAT) immunostained tissue was then analyzed in order to investigate the relationship of cholinergic perikarya, dendritic arborizations, and axonal trajectories within this cytoarchitectonic scheme. To confirm some of our cytoarchitectonic delineations, the relationships between neuronal elements staining for ChAT and tyrosine hydroxylase were investigated on tissue stained immunohistochemically for the simultaneous demonstration of these two enzymes. The PPTn consists of large, multipolar neurons, all of which stain immunohistochemically for ChAT. It is present within cross-sections that also include the A-6 through A-9 catecholamine cell groups and is traversed by catecholaminergic axons within the dorsal tegmental bundle and central tegmental tract. The dendrites of PPTn neurons respect several nuclear boundaries and are oriented perpendicularly to several well-defined fiber tracts. Cholinergic axons ascend from the mesopontine tegmentum through the dorsal tegmental bundle and a more lateral dorsal ascending pathway. A portion of the latter terminates within the lateral geniculate nucleus. It has been widely believed that the PPTn is reciprocally connected with several extrapyramidal structures, including the globus pallidus and substantia nigra pars reticulata. Therefore, the relationships of pallidotegmental and nigrotegmental pathways to the PPTn were investigated employing the anterograde autoradiographic methodology. The reciprocity of tegmental connections with the substantia nigra and entopeduncular nucleus was investigated employing combined WGA-HRP injections and ChAT immunohistochemistry. The pallido- and nigrotegmental terminal fields did not coincide with the PPTn, but, rather, were located just medial and dorsomedial to it (the midbrain extrapyramidal area). The midbrain extrapyramidal area, but not the PPTn, was reciprocally connected with the substantia nigra and entopeduncular nucleus. We discuss these results in light of other cytoarchitectonic, cytochemical, connectional, and physiologic studies of the functional anatomy of the mesopontine tegmentum. PMID- 2885348 TI - Organization of central adrenergic pathways: I. Relationships of ventrolateral medullary projections to the hypothalamus and spinal cord. AB - We studied the organization of projections from the C1 adrenergic and A1 noradrenergic cell groups in the ventrolateral medulla (VLM) to the hypothalamus and the spinal cord by using a combination of retrograde transport of fluorescent tracers and immunocytochemistry. Three issues were addressed. Neurons in the VLM that stain immunohistochemically for phenylethanolamine N-methyltransferase (PNMT) have been assumed to be adrenergic. However, the presence of PNMT immunoreactive neurons in the hypothalamus that do not stain for tyrosine hydroxylase (TH) prompted us to re-evaluate the VLM by an elution-restaining immunohistochemical procedure. We confirmed that nearly all of the rostral medullary PNMT-immunoreactive neurons also stained for TH. By contrast, in the caudal medulla, very few TH-positive neurons stained for PNMT. Neurons of the C1 group in the rostral VLM project both to the thoracic spinal cord and to the hypothalamus. To determine whether individual C1 neurons send collaterals to the hypothalamus and spinal cord, we injected different-colored fluorescent dyes (diamidino yellow or fast blue) into the thoracic spinal gray matter and either the median preoptic (MnPO) or paraventricular (PVH) nuclei of the hypothalamus. Very few double-labeled neurons were found in the VLM, indicating that hypothalamic and spinal cord projections arise from almost completely independent populations of cells. Approximately half of the neurons projecting to the spinal cord from rostral VLM were not immunoreactive for TH or PNMT, indicating that a substantial part of this projection is noncatecholaminergic. The MnPO and the PVH both receive extensive catecholaminergic inputs from the VLM. We also used fluorescent retrograde tracers to determine whether individual VLM neurons send collaterals to both hypothalamic sites. Approximately 20% of neurons projecting to the MnPO in the rostral two thirds of the VLM also sent collaterials to the PVH, nearly all of these neurons being TH-positive. The collateralization of the VLM catecholaminergic projection to the hypothalamus may provide an anatomical substrate for integration of fore-brain participation in cardiovascular regulation. In contrast, the adrenergic projection from the VLM to the intermediolateral column of the spinal cord arises from a separate population of neurons. PMID- 2885349 TI - Neuropeptide Y-immunoreactive perikarya and nerve terminals in the rat medulla oblongata: relationship to cytoarchitecture and catecholaminergic cell groups. AB - The aim of this study was to examine details of the distribution of neuropeptide Y (NPY)-immunoreactive perikarya and nerve terminals in the medulla oblongata in relation to cytoarchitectonically and functionally distinct catecholaminergic regions. The immunoperoxidase method was combined with Nissl staining to determine nuclear boundaries of transmitter-identified nerve cell bodies and to examine the relationship between populations of NPY-immunoreactive neurons and catecholaminergic cell groups (A1, A2, C1, C2, and C3) in serial sections. Previous studies using immunofluorescence have described the existence of NPY catecholaminergic immunoreactive nerve cell bodies in the brainstem. No information is currently available with regard to details of the distribution of these peptidergic neurons and nerve terminals in the functional subnuclear units of the medulla oblongata. In this study we have delineated the anatomical association of NPY immunoreactivity with cardiovascular function. Neuropeptide Y immunoreactive neurons were found located in close association with noradrenergic neurons of the A1 cell group in the caudal ventrolateral medulla oblongata, where they were usually found located dorsal to the lateral reticular nucleus (LRt). A second population of NPY-immunoreactive neurons was found located medial to the A1 cell group in the ventral subdivision of the reticular nucleus of the medulla (MdV). Neuropeptide Y-immunoreactive neurons in the rostral medulla were found located in regions corresponding to the principal distribution of adrenergic neurons in the C1, C2, and C3 cell groups. In the dorsomedial medulla (A2 region) NPY-immunoreactive neurons were localized in the area postrema (ap) and in a number of subnuclei of the nucleus of the tractus solitarius (nTS), i.e., the dorsal parasolitary region (dPSR), the dorsal strip (ds), the periventricular region (PVR), and the ventral parasolitary region (vPSR). The location of NPY immunoreactive perikarya and nerve terminals in the dorsal subnuclei of the nTS, i.e., the dPSR and ds, is of particular significance, since this distribution corresponds with the location of small adrenergic neurons as well as with the site of termination of aortic and carotid sinus nerve afferent fibers. NPY immunoreactive neurons in the dorsomedial medulla are ideally situated for receiving monosynaptic input from baroreceptor afferents and could play a key role in the central integration of cardiovascular reflexes. PMID- 2885350 TI - Periarteritis in a beagle colony. AB - Primary periarteritis, an uncommon necrotizing vasculitis in the dog, was found to affect, almost exclusively, the major branches of the coronary arteries in a number of young beagle dogs. The arteritis was mainly distributed in the proximal segment of the right coronary artery. Immunocytochemical studies failed to identify immunoglobulin deposits in the lesions and the cause of the arteritis remains unknown. It is important to be aware of this spontaneous condition and its regional distribution since certain cardiovascular drugs may also produce necrotizing arteritis at similar sites. PMID- 2885351 TI - A focus on cancer: development of a course on prevention and early detection. PMID- 2885352 TI - [Pain and endogenous analgesic mechanisms in the body's adaptive activities]. PMID- 2885353 TI - [Mechanism of the formation of a receptor response]. PMID- 2885354 TI - Effect of beta-adrenergic blockade on exercise performance in patients with chronic atrial fibrillation. AB - Beta-adrenergic blocking agents are commonly used in combination with digitalis to control excessive heart rate during exercise in patients with chronic atrial fibrillation. However, little is known about the effect of beta-adrenergic blockade on exercise capacity in these patients. Accordingly, a randomized, double-blind, cross-over placebo-controlled study was performed to assess the efficacy of celiprolol, a new cardioselective beta-blocker with partial intrinsic sympathomimetic activity, on exercise performance in nine men with chronic atrial fibrillation. All but one patient was receiving maintenance digitalis during the study. Heart rate, blood pressure and gas exchange variables were measured at rest and during treadmill exercise testing while the patients were receiving maintenance celiprolol or placebo. Significant reductions in heart rate and systolic blood pressure compared with control values were observed at submaximal exercise, at the gas exchange anaerobic threshold and at maximal exertion while the patients were taking celiprolol. However, oxygen uptake at the gas exchange anaerobic threshold during celiprolol therapy was 12.3 versus 14.0 ml oxygen/kg per min during placebo administration (a 12% difference, p less than 0.01). Similarly, oxygen uptake at maximal exertion during celiprolol therapy was 17.6 versus 21.0 ml/kg per min during placebo administration (a 16% difference, p less than 0.01). Treadmill time was also reduced during the celiprolol phase compared with placebo (11.3 versus 10.3 minutes; a 19% difference, p less than 0.01). These results indicate that in patients with atrial fibrillation the major beneficial effects of beta-adrenergic blockade--reduced submaximal and maximal exercise heart rate and blood pressure--must be weighed against the decrease in exercise capacity. PMID- 2885355 TI - Effect of cetirizine, a new histamine H1 antagonist, on airway dynamics and responsiveness to inhaled histamine in mild asthma. AB - Cetirizine, a major human metabolite of hydroxyzine, preserves the histamine H1 antagonist activity of the parent compound but poorly penetrates the blood-brain barrier, thus minimizing sedative and anticholinergic effects. In 10 young (mean age 27.7 years) subjects with mild asthma (FEV1 greater than 70% predicted), we evaluated the bronchodilator and protective efficacy of 5, 10, and 20 mg of cetirizine against bronchospasm induced by histamine inhalation (0.03 to 20 mg/ml) in comparison with placebo and hydroxyzine, 25 mg, using a random, double blind crossover design. The provocative concentration of histamine causing a 20% decline in FEV1 for all 10 subjects from the postdiluent control value was more than fourfold greater after each active drug than after placebo. Cetirizine, 5 to 20 mg, provided significantly greater protection against histamine-induced bronchospasm than hydroxyzine (p less than 0.001); moreover, a dose-dependent protective effect was noted with cetirizine. Significant bronchodilation was also found: at 60 minutes, FEV1 increased significantly after all active antihistamines compared to placebo and after 20 mg of cetirizine compared to hydroxyzine (p less than 0.05). FEV1 increased significantly at 120 minutes after hydroxyzine and after cetirizine in both the 20 and 10 mg doses compared to placebo (p less than 0.05). We conclude that in subjects with mild asthma, orally administered cetirizine provides significant dose-dependent protection against histamine-induced bronchoconstriction, which in the doses studied is superior to that produced by the parent compound, hydroxyzine. In addition, cetirizine in 5 to 20 mg doses causes acute bronchodilation. These results suggest a possible role of cetirizine in asthma therapy. PMID- 2885356 TI - Sedative effects of antihistamines. AB - The central effects of a newly developed, long-acting H1 antihistamine, loratadine (10 and 40 mg), were compared with those of a standard H1 antihistamine, diphenhydramine (50 mg three times a day) with measures of performance and daytime sleepiness (multiple sleep latency test). Sixteen healthy adults (six women and 10 men), 19 to 35 years of age, received each of the drugs and placebo for 2 days, separated by 5 days at home. Each day, the drug or placebo was administered at 8 A.M. and 12 and 4 P.M. Diphenhydramine was administered in three equal doses (50 mg), and loratadine was administered in a single dose followed by two placebo doses. Mean latency to sleep on tests done at 9 and 11 A.M. and 1, 3, and 5 P.M. was reduced significantly with diphenhydramine compared to placebo, whereas neither loratadine dose reduced sleep latency. Performance measured at 9:30 P.M. and 1:30 P.M. with a battery of tests, including reaction time, vigilance, digit symbol substitution, and symbol copying tasks demonstrated a significant reduction in symbols copied and digits substituted after diphenhydramine compared to both loratadine doses. These results demonstrate that loratadine (10 and 40 mg doses) did not have clinically significant central nervous system activity, whereas diphenhydramine increases sleepiness and disrupts performance efficiency. PMID- 2885357 TI - A double-blind evaluation of skin test suppression produced by two doses of terfenadine. AB - For some patients, terfenadine, in the currently recommended dose of 60 mg twice daily (bid), may be only modestly effective in the treatment of allergic rhinitis. In a double-blind placebo-controlled crossover study of 12 patients, a larger dose (300 mg bid) was evaluated for its suppression of titrated skin tests to histamine and compound 48/80 to determine whether this regimen might result in greater suppression while it maintained the freedom from side effects of the presently recommended dose. In seven patients, skin test suppression by these two doses of terfenadine each administered for 3 days, was compared to that produced in an earlier study by 3 days of treatment with chlorpheniramine (8 mg three times a day). The 300 mg bid terfenadine regimen produced significantly greater skin test suppression (p less than 0.05) than the currently recommended 60 mg bid dose. There was no significant difference in side effects between the two doses, and neither active treatment regimen produced more side effects than placebo treatment. Both doses of terfenadine suppressed cutaneous reactivity significantly more than had chlorpheniramine. It is concluded that the presently recommended dose of terfenadine produces submaximal skin test suppression and that further studies are needed to investigate the clinical efficacy and safety of larger doses of terfenadine in the treatment of allergic rhinitis. PMID- 2885358 TI - Intrathecally administered angiotensin II increases sympathetic activity in the rat. AB - The possibility that angiotensin II (AII) functions as an excitatory transmitter on sympathetic preganglionic neurones was tested in anaesthetized rats. Drugs were administered intrathecally whilst recording blood pressure, heart rate and sympathetic activity in splanchnic or renal nerves. Intrathecal AII (20 microliters, 10(-5) M) caused a significant increase in blood pressure of 13% +/- 3 and in sympathetic activity of 15% +/- 5. Intrathecal AII (20 microliters, 10( 3) M) caused larger increases in blood pressure of 22% +/- 3 and in sympathetic activity of 25% +/- 3. The magnitude of the response was dependent on the location of the catheter tip within the subarachnoid space T9-T11 being best for the above changes. Preceding intrathecal AII with the AII antagonist Saralasin (20 microliters, 10(-3) M) also given intrathecally prevented the changes. An increase in sympathetic nerve activity brought about reflexly by a drop in blood pressure of 45-47 mm Hg was almost halved by intrathecal Saralasin. Peak plasma counts (less than 5% of total) of [3H]AII in the blood after intrathecal injection occurred 2 min after the peak changes in sympathetic activity and blood pressure. Counts of [3H]AII in the spinal cord showed that 81% of recovered label was within one segment on either side of the catheter tip. It is concluded that AII has an excitatory action on sympathetic neurones in the spinal cord. PMID- 2885359 TI - Separate areas of rat medulla oblongata with populations of serotonin- and adrenaline-containing neurons alter blood pressure after L-glutamate stimulation. AB - Separate populations of serotonin- and adrenaline-containing neurons exist in the ventrolateral medulla oblongata and project to the intermediolateral cell column of the spinal cord. The medullary serotonin nuclei appear to constitute a heterogeneous group with diverse effects on arterial pressure. Microinjections of sodium glutamate (which excites cell bodies but not axons of passage) made in the area of the ventrolateral serotonin cells evokes an increase in arterial pressure which is abolished by prior 5,7-dihydroxytryptamine (5,7-DHT) treatment. In contrast, glutamate microinjection in the area of the serotonin-containing cell bodies in the midline of the medulla evokes falls in arterial pressure and these responses are attenuated by pretreatment with 5,7-DHT. Glutamate microinjection made in the ventrolateral medulla in the area of the adrenaline-containing cells, evokes increases in arterial pressure which are not altered by 5,7-DHT pretreatment. After ablation of the area of the adrenaline-containing cells by electrolytic lesion, the pressor function of the ventrolateral serotonin containing cells is still observed. These results suggest that although the serotonin-containing neurons of the ventrolateral medulla are closely aligned with the ventrolateral adrenaline area, the serotonin cell groups and the cells of the adrenaline area exert their pressor actions independently. PMID- 2885360 TI - Excitatory innervation of the rabbit rectococcygeus muscle by enteric nerves from the terminal large intestine. AB - The rectococcygeus muscle extends from the longitudinal layer of the external muscles of the terminal colon, anchoring the large intestine to the coccygeal vertebrae. The muscle is thought to assist the colon during defaecation, drawing the large intestine partly into the pelvic cavity. In the rabbit, many fine nerves run between the wall of the colon and a ganglionated nerve plexus on the ventral face of the rectococcygeus muscle. Extracellular recordings of evoked and spontaneously occurring multiunit discharges from these nerve bundles indicated that they may take their origin from the enteric nervous system of the large intestine. Enteric nerves (as we have called them) conducted bursts of spontaneously occurring multiunit discharges, each burst associated with a twisting movement of the rectococcygeus and the colon. Electrical stimulation of enteric nerves elicited cholinergically mediated contractions of the rectococcygeus; however, nerve stimulation failed to elicit relaxation of muscle tone induced by carbachol. Therefore, enteric nerves appeared to supply the rectococcygeus with an excitatory innervation only. These excitatory nerves appeared to remain uninterrupted by a ganglion synapse as they travelled to the rectococcygeus. Stimulation of enteric nerves caused the left and right hemirectococcygeal muscle strips to twist and deform the colo-rectal region to which they were attached. From these results, it is suggested that the rectococcygeus may delay the movement of luminal contents from colon to rectum by forming a weak valve which partially occludes the colo-rectal region. The enteric nerves to the rectococcygeus may assist in the maintenance of continence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885361 TI - Meeting report: Th autonomic nervous system in health and disease. PMID- 2885362 TI - Neuroleptics and behavior: a comparative study. PMID- 2885363 TI - Postnatal change of cardiac function in lambs: effects of ganglionic block and afterload. AB - This study characterizes the maturational change of cardiac function in unanaesthetized lambs from 1 day to 6 months of age. The cardiac function curve, the relationship between left ventricular output (Qco) and left ventricular end diastolic pressure, was studied in lambs of ages 1 day, 2-3 days, 7-8 days, 1 month, 3 months and 6 months. Cardiac output was measured by thermodilution while left ventricular end diastolic pressure was either raised by infusion of 5% glucose, or lowered by haemorrhage. At elevated left ventricular end diastolic pressure, cardiac output tended to reach a plateau of approximately 300 ml/min per kg in lambs less than 1 week of age and 200 ml/min per kg in lambs older than 1 month. Cardiac function was depressed by total ganglionic block in 1-3 days-old lambs, but not in lambs older than 1 week. Heart rate decreased in response to ganglionic block in lambs up to 1 week of age, but it increased in lambs 3-6 months old. Increases in afterload with methoxamine infusion during ganglionic block further depressed cardiac function in all age groups of lambs. The stroke work curve was shifted downward by hexamethonium and returned back to control level by methoxamine. We conclude that newborn cardiac output is near maximum even at 1 month of age. Sympathetic activity and circulating catecholamines help maintain cardiac function in 1-3 days-old lambs. Cardiac function is sensitive to afterload in lambs of all ages studied. PMID- 2885364 TI - Selective loss of hormonal induction of glutamate transport in primary cultures of hepatocytes from rats treated with CCl4. AB - A protocol for the mass isolation and successful cultivation of hepatocytes from the acinar zones 1 and 2 is described. The hepatocyte suspensions isolated from rats pretreated with CCl4 contain less than one-tenth of control levels of the perivenous marker enzyme glutamine synthetase, as judged by immunocytochemistry and enzyme activity excluding contamination by hepatocytes from zone 3. In culture these hepatocytes form morphologically and functionally intact monolayers. They synthesize urea and glucose at rates above those of controls, but are unable to produce glutamine. These results demonstrate the suitability of this culture system for the investigation of hepatic functions that are characteristic of cells from the periportal and midzonal part of the acinus. An interesting feature of these cultures is the failure of dexamethasone to induce the uptake of glutamate while the hormonal induction of the amino acid transport systems A and N and of tyrosine aminotransferase is not affected. PMID- 2885365 TI - Psychomotor effects of astemizole and chlorpheniramine, alone and in combination with alcohol. AB - Road traffic accidents are a leading cause of mortality and morbidity, and their association with alcohol and drugs such as minor tranquillizers is well established (Seppala et al., 1979). There is also epidemiological evidence to associate the older, sedative antihistamines with motorcycle accidents (Skegg et al., 1979). Astemizole is a recently introduced H1-antagonist which, unlike older antihistamines, does not cause central nervous system sedation. The present study was designed to compare the effects of astemizole and chlorpheniramine, alone and in combination with alcohol, on an objective measure of psychomotor performance relating to car-driving ability. PMID- 2885366 TI - A clinical and neurophysiological evaluation of clotiazepam, a new thienodiazepine derivative. AB - The effects of 3 different dosages of clotiazepam, a new short-acting thienodiazepine derivative, were evaluated by using psychometric ratings and EEG spectrum analysis. A random double-blind study versus placebo was performed on 8 patients affected by generalized anxiety disorder (DSM III). The effects of acute administration of clotiazepam 5 mg, 10 mg, 20 mg and placebo per os were evaluated by using HRSA and a time-signed semiquantitative scale for anxiety. The results of the trial confirm the effectiveness of clotiazepam in the treatment of anxiety symptoms, mainly in the reduction of peak anxiety levels, with dose dependent characteristics. The modifications of the EEG parameters which resulted were dose-dependent and short-lasting with slight sedative findings. PMID- 2885367 TI - A controlled clinical trial of tiaspirone in schizophrenia. AB - The antipsychotic efficacy of tiaspirone, a new atypical antipsychotic agent, was compared to standard neuroleptics, in a single-blind cross-over study. Nine actively psychotic schizophrenic patients entered the study and 6 completed it. Significant overall improvement, on BPRS and CGI ratings, occurred by week 4, on both--tiaspirone and standard neuroleptics. There were no significant differences between tiaspirone and standard neuroleptics, in their antipsychotic efficacy. In keeping with the preclinical profile of tiaspirone, no extrapyramidal symptoms (EPS) were observed with tiaspirone. Two patients showed EPS on standard neuroleptics. Five of the 6 patients showed mild transient elevation of liver enzymes while on tiaspirone. Liver enzymes returned to normal within 3 weeks of discontinuation of tiaspirone. Tiaspirone appears to be a promising new antipsychotic agent that may be clinically effective without causing extrapyramidal syndromes. PMID- 2885368 TI - The evaluation of an ultrasound detector (UD) in the measurement of oro-facial dyskinesia. AB - An ultrasound detector (UD) was compared with a clinical rating (CR) scale in the assessment of oro-facial movements in 23 chronic schizophrenic patients and 23 normal subjects over a period of 4 weeks. The apparatus distinguished well between normal volunteers and dyskinetic patients. There were also highly significant correlations between UD scores and clinical ratings. The results thus confirm both the construct and concurrent validity of the technique. Nevertheless, there was significant variation in the UD scores for some patients between assessments. A technical problem was the inability of some patients to cooperate for more than 30 seconds. The scores of the normal subjects were consistent. With further development and repeated 30-second assessments the technique might be of value in the ascertainment of early dyskinesia in patients at risk and also in measuring drug effects. PMID- 2885369 TI - Immunoelectron microscopic demonstration of pancreatic polypeptide in midgut epithelium of hematophagous dipterans. AB - Midguts of mosquitoes, Aedes aegypti and Anopheles stephensi, and of the tsetse fly, Glossina morsitans morsitans, as well as guinea pig pancreas, were prepared for electron microscopy by using low-temperature embedding in Lowicryl K4M. Rabbit antiserum to bovine pancreatic polypeptide (PP) crossreacted with secretory granules of pancreatic PP-producing cells and of the clear cells in mosquito gut. Rabbit antiserum to human somatostatin crossreacted with the control tissue, guinea pig pancreas D-cells, but not with the mosquito clear cells. None of the antisera used showed a distinct reaction with the endocrine like cells of tsetse fly midgut. Positive reactions were revealed by gold as electron-dense marker. The gold particles were coated with protein A-gold or goat antibodies to rabbit immunoglobulin. PMID- 2885370 TI - Chemoarchitectonics of the brainstem in infrared sensitive and nonsensitive snakes. AB - The crotaline snake Agkistrodon possesses infrared receptors, whereas the colubrid Elaphe quadrivirgata does not. We compared the histochemical activity of succinate dehydrogenase (SDH), monoamine oxidase (MAO), and acetylcholinesterase (AChE) in the brainstem of these 2 species, by the method of Nachlas et al. (1957), Glenner et al. (1957), and Koelle and Friedenwald (1949), respectively, and made the following observations. Visual system: The tectum opticum (TO) exhibited strong or moderate AChE and SDH activity in areas receiving retinal projections, i.e. the str. zonale (sz), str. fibrosum et griseum superficiale (sfgs), and narrow areas between small tight fasciculi of the tr. opticus. The sfgs was divided into 2 sublayers, a superficial and a deep, by the intensity of AChE activity. The deep sublayer of the sfgs and sfc of Agkistrodon were stained more strongly than other layers. Numerous fibers within the TO showed MAO activity. The entire sfgs of Agkistrodon was thinner than in Elaphe. The nucl. posterodorsalis showed moderate AChE, and weak SDH and MAO activity in Agkistrodon, but lack of AChE, weak SDH, and moderate MAO activity in Elaphe. Infrared system: This system was present only in Agkistrodon. The nucl. of the lateral descending trigeminal tract (dlV) and the nucl. reticularis caloris (rc) showed to moderate SDH activity in the main neuropil and/or perikarya. These nuclei were not conspicuous in AChE preparations. The marginal neuropil of the dlV had weak SDH, and moderate AChE and MAO activity. Common sensory trigeminal system: Moderate activity of the 3 enzymes was seen in the nucl. tr. descendens n. trigemini (dl). In the dorsomedial part of the nucl. interpolaris, the round limited portion was stained strongly for SDH and AChE. Cells of the nucl. tr. mesencephalicus n. trigemini showed strong SDH and AChE activity. Other regions: In Elaphe, there was strong to moderate AChE and SDH activity in the nucl. of the fasciculus longitudinalis medialis, nucl. centralis superior, raphe nuclei, and reticular nuclei, but only weak activity in Agkistrodon. We also found the following similarities in the 2 species. Strong to moderate AChE and SDH activity was observed in the motor nuclei of the cranial nerves, pretectal nuclei excepting the nucl. posterodorsalis, nucl. opticus basalis, and nucl. posterolateralis tegmentalis. Strong to moderate activity of the 3 enzymes together was detected in the nucl. interpeduncularis as found in other animals previously studied, and in the nucl. commissurae cornae dorsalis, nucl. cochlearis angularis, and the molecular and granular layer of the cerebellum.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2885371 TI - Thy-1-negative and Ly-1-negative variants of T cells produce interleukin 2 in response to mitogens. AB - IL 2 production by T cell variants, which lack the Thy-1 or Ly-1 surface glycoproteins, was studied. Cross-linking of the Thy-1 molecule resulted in IL 2 production by the EL4 thymoma and by a T cell hybridoma, suggesting that Thy-1 may play a role in T lymphocyte triggering. To further study the functional role of this molecule, Thy-1-negative variants were selected and analyzed for IL 2 production in response to phorbol-12-myristate-13-acetate (PMA) or to Con A. It was demonstrated that in spite of their failure to express Thy-1, the Thy-1 negative clones were capable of IL 2 production. These results indicated that although Thy-1 cross-linking triggers cell activation, a signal provided by Thy-1 is not indispensable for cell activation by mitogens. The T cell tumor line LBRM331A5 responds synergistically to IL 1 and PHA by releasing IL 2. It was demonstrated that anti Ly-1 monoclonal antibodies and PHA co-stimulated LBRM331A5 cells, as did IL 1 plus PHA. Thus, anti Ly-1 antibodies mimic the effect of IL 1, suggesting a role for Ly-1 antigen in T cell activation, perhaps by serving as an IL 1 receptor or as an associated molecule. To further study the functional role of Ly-1 and its relation to IL 1 receptor, Ly-1-negative variants of the LBRM331A5 cell line were selected and analyzed for IL 2 production in response to PHA plus IL 1. It was demonstrated that the Ly-1-negative clones were capable of IL 2 production as efficiently as Ly-1-positive clones. These results indicate that the Ly-1 and IL 1 receptor are distinct molecules, which are involved in different activation pathways. PMID- 2885372 TI - Mouse lymphotoxin and tumor necrosis factor: structural analysis of the cloned genes, physical linkage, and chromosomal position. AB - Lymphotoxin (LT) and tumor necrosis factor (TNF) are cytotoxic and immunoregulatory lymphokines which have similar activities but are produced by different cell types. We have cloned the murine LT and TNF genes from a lambda:mouse DNA recombinant library, using as probes synthetic oligonucleotides defined by portions of the human LT or TNF cDNA sequences. Analysis of the genomic clones indicates that the LT and TNF genes are physically linked, i.e., approximately 1.2 kb separates the 3' end of LT from the 5' end of TNF genes. By using, first, a series of recombinant inbred lines, and second, a series of H-2 recombinant congenic strains, we determined that the LT/TNF gene cluster lies on chromosome 17, closely linked to the H-2D end of the murine H-2 complex. Comparison of the primary sequence of murine and human LT revealed that the intron-exon structure of murine LT is similar in these two species. Comparison of the predicted amino acid sequences of murine and human LT indicates that the proteins are about 72% homologous with much greater sequence conservation in regions encoding the COOH-terminal portion. Comparison of the 5' flanking sequence of LT to a number of genes that are specifically expressed in activated T cells reveals a number of conserved sequences that may play a role in control of these genes. PMID- 2885373 TI - Molecular mapping of class II polymorphisms in the human major histocompatibility complex. I. DR beta. AB - We have studied 27 cell lines homozygous by consanguinity for the major histocompatibility complex to establish the restriction fragment length polymorphism (RFLP) patterns seen with six different restriction enzymes (Bam HI, Bg1 II, Eco RI, Hinc II, Hind III, Pvu II) and DR beta chain probes. The probes used were a full-length cDNA DR beta probe and a probe specific for the 3' untranslated region. The RFLP obtained represent the first standard patterns for the individual haplotypes DR1 through 7 and DR9 as defined by genetically homozygous lines. The patterns obtained reflect the DR specificities closely, as well as the DRw52 and DRw53 specificities. These latter specificities are associated with the most prominent patterns of RFLP. Bands are present which are unique for the haplotypes DR1, DR2, DR4, DR7, DRw52, and DRw53, and could be used for typing these haplotypes in heterozygotes. Subtypes can be identified for all of the haplotypes except DR1. These subtypes indicate that there is an extensive amount of polymorphism in the DR subregion that has not been identified serologically. PMID- 2885374 TI - Molecular mapping class II polymorphisms in the human major histocompatibility complex. II. DQ beta. AB - The restriction fragment length polymorphisms have been determined for six restriction enzymes (Bam HI, Bg1 II, Eco RI, Hinc II, Hind III, and Pvu II) and a DQ beta probe on 25 cell lines that are homozygous by consanguinuity at the MHC. These patterns reflect both DR haplotypes and DQ types of the cells tested. At least one non-polymorphic band is present in all the cell lines with every restriction enzyme except Hinc II. This band most probably represents DX beta hybridization. The polymorphic bands indicate that more polymorphism exists in the DQ subregion than is predicted serologically. Each DR haplotype is associated with a unique set of restriction fragments except for DR2 and DR6. The patterns are largely consistent within each DR haplotype. In addition, some bands reflect the established DQ specificities DQw1 and DQw2. Individual bands can be identified that are unique to the haplotypes DR1, DR4, DR5, and DR6 and the DQw1- and DQw2-associated haplotypes. Subdivisions of haplotypes can be identified with this probe. In particular, MVL (DR1), Akiba (DR2), QBL (DR3), FPF (DR5), and APD (DR6) have polymorphisms that distinguish them from other members of their DR haplotype. PMID- 2885375 TI - Conserved organization of the murine immunoglobulin epsilon gene region: restriction endonuclease maps and switch-region nucleotide sequence. AB - Various inbred mouse strains showed remarkable conservation of organization in the epsilon germline region as determined by restriction mapping. Restriction fragment length polymorphisms (RFLP) were seen in the epsilon gene region for only two of eight restriction enzymes tested. Furthermore, the RFLP did not correlate with the IgE-response phenotype for the murine strains SJL, SJA, C57BL/6, BALB/c, A/ST, and A/J. The IgE class-switch region (S epsilon) DNA from an SJL genomic clone was sequenced and was compared with S epsilon sequences from BALB/c mice. These S epsilon sequences were at least 95% homologous. Most of the S epsilon sequence differences observed between the two strains were single base pair substitutions, deletions, or insertions. The largest difference between the S epsilon sequences resulted from an insertion of seven contiguous bases seen in the SJL S epsilon region. PMID- 2885376 TI - In vivo T cell depletion regulates resistance and morbidity in murine schistosomiasis. AB - These studies assessed the roles of subpopulations of T lymphocytes in inducing and modulating resistance to schistosomiasis and thereby influencing subsequent morbidity. C57BL/6 mice were depleted in vivo of Lyt-1+, Lyt-2+, and L3T4+ cells by the daily administration of monoclonal antibodies. The development of protective immunity, induced by exposure to irradiated Schistosoma mansoni cercariae as expressed in depleted animals, was compared to that demonstrated in undepleted, normal, and congenitally athymic C57BL/6 mice. The development of morbidity was determined by spleen weight, portal pressure and reticuloendothelial system activity. The results indicated that depletion of specific subpopulations of T lymphocytes minimally affected the primary development of parasites; however, depletion strongly influenced the development of resistance to the parasite and subsequent morbidity due to infection. Depletion of T lymphocytes by anti-Lyt-1+ or anti-L3T4+ antibody decreased the development of resistance, antibody and delayed-type hypersensitivity directed against schistosome antigens. Morbidity due to disease was increased. Depletion of Lyt-2+ cells produced opposite changes with augmented resistance and reduced morbidity. Congenitally athymic mice developed minimal resistance and morbidity. Moreover, resistance was inversely related to the morbidity shown by a given animal. These studies indicate that the development of protective immunity to S. mansoni cercariae is regulated by discrete subpopulations of T lymphocytes. The feasibility of decreasing morbidity by increasing specific immunologically mediated resistance is suggested. PMID- 2885378 TI - Effect of retinoic acid on cornified envelope formation: difference between spontaneous envelope formation in vivo or in vitro and expression of envelope competence. AB - A large number of cross-linked envelopes form spontaneously when cell lines derived from chemically induced mouse skin papillomas are cultured in medium containing 1.2 mM calcium. This phenomenon is associated with high activity of the cross-linking enzyme, epidermal transglutaminase (TGase). The influence of retinoic acid (RA) on envelope formation was studied in detail in a papilloma cell line, PE. Retinoic acid (3 microM) completely blocked cornified envelope (CE) production but reduced TGase activity only 50%. A rabbit antiserum was produced against sonicated CEs isolated from newborn mouse skin. On Western blots of epidermal extracts, diffuse staining was observed for particulate proteins of suprabasal, but not basal, cells and similar immunoreactive material was absent from the cytosolic fraction of both cell layers. The antibody also recognized particulate proteins from PE cells induced to differentiate by calcium, but not from cells grown in the presence of high calcium and RA. The antiserum appears to recognize partially cross-linked CE precursor proteins judging by the diffuse staining, the molecular weight range of the proteins stained, and their origin in the particulate cellular fraction. Cross-linked envelopes could be induced in RA treated PE cells by permeabilization with 0.75 M NaCl or 50 micrograms/ml A23187. However, this treatment failed to cause the appearance of proteins recognized by the antiserum. Preincubation of the antiserum with purified fragments of CEs from newborn mouse epidermis, but not with cross-linked envelopes from permeabilized, RA-treated PE cells, removed immunoreactivity. These results indicate that the cross-linked envelopes formed in RA-treated cells after permeabilization lack a set of proteins contained in CEs from stratum corneum and may even be composed of different proteins. Retinoic acid appears to prevent CE formation in part by inhibiting activation of epidermal TGase but in addition by influencing the synthesis of precursor proteins. PMID- 2885379 TI - P fimbriae and other virulence factors in Escherichia coli urosepsis: association with patients' characteristics. PMID- 2885377 TI - Development and preliminary evaluation of a slide latex agglutination assay for detection of Clostridium perfringens type A enterotoxin. AB - A slide latex agglutination (SLA) assay was developed for rapid screening for Clostridium perfringens type A enterotoxin (CPE). SLA specifically detected CPE added to buffer or normal feces (sensitivity limit of 1 microgram CPE/g feces). Using clinical fecal samples from C. perfringens food poisoning cases, a strong correlation was shown between SLA results and results from other CPE assays and between SLA results and illness status. PMID- 2885380 TI - Phagolysosome formation by polymorphonuclear neutrophilic leukocytes after ingestion of Escherichia coli that express type 1 pili. PMID- 2885381 TI - Inhibition of growth of Entamoeba histolytica by allicin, the active principle of garlic extract (Allium sativum). PMID- 2885383 TI - Effects of alpha and theta toxins from Clostridium perfringens on human polymorphonuclear leukocytes. AB - Two toxins, alpha (phospholipase C) and theta (oxygen-labile hemolysin), were purified from Clostridium perfringens type A and assayed for toxic effects on human polymorphonuclear leukocytes (PMNLs). Crude preparations containing both toxins totally inhibited chemotaxis and chemiluminescence responses of PMNLs and reduced PMNL viability. Purified alpha toxin did not alter PMNL viability, chemotactic responsiveness, or morphology but did enhance opsonized zymosan induced PMNL chemiluminescence over a wide range of toxin concentrations. theta Toxin, at 12.5 hemolytic units (HU) per 10(5) PMNLs, reduced cell viability and induced marked PMNL morphological changes. Concentrations of theta toxin between 4 and 32 HU per 10(5) PMNLs inhibited PMNL chemiluminescence in a dose-dependent manner, whereas a lower concentration enhanced the PMNL chemiluminescent response to opsonized zymosan. Effects on chemotaxis were also dose dependent. Increased PMNL random migration was observed at a concentration of theta toxin of 0.06 HU per 2.5 X 10(5) PMNLs (P less than .05), whereas concentrations of greater than 0.08 HU per 2.5 X 10(5) PMNLs reduced both directed and random migration (P less than .05). PMID- 2885382 TI - Detection of scrapie-associated fibrils (SAF) and SAF proteins from scrapie affected sheep. AB - Scrapie-associated fibrils (SAF) were detected by negative-stain electron microscopy in the brains (by two different isolation procedures) and spleens of sheep naturally and experimentally infected with scrapie. Although the numbers of SAF varied from case to case, the yield of SAF from brains of naturally affected sheep was lower than that from experimentally affected sheep. SAF-specific, protease-resistant proteins (PrPs) were detected by silver staining and western blot analysis in most samples of brain from experimentally affected sheep. PrPs, however, could be detected in only a limited number of natural cases of sheep scrapie because of the lower yields of SAF. PrPs from sheep SAF appear biochemically and antigenically similar to PrPs from other species infected with unconventional agents. This study further establishes the unique association of SAF and PrPs with natural or experimentally induced scrapie in its natural host. PMID- 2885384 TI - Use of monoclonal antibodies to identify, characterize, and purify a 96,000 dalton surface antigen of pathogenic Entamoeba histolytica. AB - We identified and partially characterized a surface antigen of Entamoeba histolytica by using seven monoclonal antibodies obtained after injecting mice with a pathogenic strain of amoeba. An intrinsically radiolabeled 96,000-dalton antigen was immunoprecipitated by five of the seven monoclonal antibodies; this antigen was present in three strains of E. histolytica. The antigen was situated on the external surface of E. histolytica, as demonstrated by agglutination and immunofluorescence staining of live amoeba and by immunoprecipitation of iodinated trophozoite antigen. All seven monoclonal antibodies were specific for E. histolytica and failed to react in an ELISA with Trichomonas vaginalis, Tritrichomonas foetus, Giardia lamblia, Acanthamoeba castellonii, and Entamoeba invadens. Two monoclonal antibodies were used to purify the antigen: the purified antigen was identical when antibody binding to live organisms or antibody reactive with nonviable organisms was used for purification. PMID- 2885385 TI - [Human placental glutathione transport mechanism]. AB - The placental transport mechanism of glutathione (GSH) was investigated using microvillous membrane vesicles prepared from human term placenta. Using (3H glycine)-labeled-GSH, it was clarified that GSH in the extravesicular compartment of placental microvillous membranes was rapidly degraded by gamma-GTP (gamma glutamyltranspeptidase) and resulting amino acid, and 3H-labeled-glycine was actively transported via a sodium cotransport system. AT-125 treated microvillous membrane vesicles almost entirely lost its gamma-GTP activity, and showed intact GSH transport. Using AT-125 treated microvillous membrane vesicles, it was revealed that GSH was transported across the microvillous membrane as an anion via a membrane potential-dependent mechanism. These results indicated that gamma GTP which existed in microvillous membrane played a role in GSH metabolism and that intracellular GSH was translocated out of the syncythiotrophoblast cell into the maternal blood space via a specific carrier in microvillous membrane because the GSH concentration was higher in intracellular than extracellular and extracellular membrane potential was positively charged. PMID- 2885386 TI - Glutamic acid in the treatment of tinnitus. PMID- 2885387 TI - Characterization of two distinct transglutaminases of murine bone marrow-derived macrophages: effects of exposure of viable cells to cigarette smoke on enzyme activity. AB - The present study examines the effects of water soluble extracts of gas-phase cigarette smoke on intracellular transglutaminase activities of intact, murine, bone marrow-derived macrophages maintained in culture. Western blotting of cell lysates utilizing noncross-reactive antisera indicate that mouse bone marrow derived macrophages contain both tissue-type transglutaminase and factor XIII associated transglutaminase. This finding is also supported by data indicating that the intracellular transglutaminase activity of these cells contains thrombin dependent and -independent components. Macrophages incubated with cigarette smoke solutions for 15 minutes at 37 degrees C display a dose-dependent decrease (maximum inhibition = 55%, p less than .001) in tissue-type (thrombin independent) transglutaminase activity, as compared to control cells incubated with phosphate-buffered saline. Factor XIII (zymogen) is not inactivated following incubation of macrophages with smoke extracts. Smoke exposure under the conditions employed has no effect on either cell viability or adherence. Incubation with 2 microM retinoic acid for 24 hours leads to a modest (2-fold) induction of tissue transglutaminase, but does not induce factor XIII; in contrast, incubation with 10% homologous serum for 24 hours results in a decrease in factor XIII, but does not affect tissue transglutaminase. These data indicate that: bone marrow-derived macrophages contain factor XIII as well as tissue-type transglutaminase; and gas-phase cigarette smoke can inactivate tissue transglutaminase within viable murine bone marrow-derived macrophages, but cannot inactivate zymogenic factor XIII. PMID- 2885388 TI - Determination of the quantity of acetyl CoA carboxylase by [14C]methyl avidin binding. AB - Conditions are described under which monomeric [14C]methyl avidin binds to SDS denatured biotin enzymes and remains bound through polyacrylamide gel electrophoresis. The location of radioactive proteins on the dried gel was determined by fluorography and their identity was established by subunit molecular weight. The relative quantity of bound radioactive avidin, stoichiometrically equivalent to the molar quantity of biotin protein, can be determined by scanning the fluorograph with a soft laser densitometer. To determine the absolute quantity of biotin protein, the radioactive areas of the dried gel were cut out, resolubilized, and assayed for radioactivity. Since the specific radioactivity of the [14C]methyl avidin was known, the quantity of avidin bound and therefore the quantity of biotin enzyme could be calculated. The method is illustrated by the analysis of purified acetyl CoA carboxylase and is applied to the analysis of biotin enzymes in isolated rat liver mitochondria. PMID- 2885389 TI - Effects of bunazosin and propranolol on ventricular arrhythmias in dogs with hypokalemia. AB - The arrhythmogenic mechanism in dogs with hypokalemia was investigated in relation to the effects of an alpha 1-blocking agent and a beta-blocking agent. Hypokalemia was induced by inserting an ion-exchange resin into the colon. In the hypokalemia group, nine out of 17 dogs with arrhythmia ratios of over 10% (that is the percentage of the number of ventricular ectopic beats divided by the total number of heart beats during 5 min, after 10 micrograms/kg of epinephrine injection) were observed. In the control group (n = 13), which maintained normal serum K+ levels, only one dog showed an arrhythmia ratio of over 10%. Dogs with lower serum K+ levels showed higher arrhythmia ratios. The Ca2+ content of heart mitochondria, considered to be a reflection of intracellular Ca2+ concentration, was 24.4 +/- 5.7 nmoles/mg protein in the control group 5 min after epinephrine injection, while that of the hypokalemia group was increased to 35.0 +/- 13.4. A good reciprocal correlation between the concentration of serum K+ just before epinephrine injection and mitochondrial Ca2+ content was observed in the hypokalemia group (r = -0.79), while in the control group, no correlation was observed. Clear correlation between mitochondrial Ca2+ content and the arrhythmia ratio was also observed in the propranolol group. Pretreatment with bunazosin, an alpha 1-"blocker," effectively prevented the increase in mitochondrial Ca2+ content, and reduced the arrhythmia ratio. On the other hand, pretreatment with propranolol, a beta-"blocker," did not affect the mitochondrial Ca2+ content and the arrhythmia ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885391 TI - Detection of a new Msp I restriction fragment length polymorphism in the apolipoprotein A-I gene. AB - We report the existence of a Msp I restriction fragment length polymorphism in the first intron of the apolipoprotein A-I gene that is different from the one described by Seilhamer et al. (DNA 3, 309 (1984)). Size comparison of the newly discovered Msp I fragment with a restriction map of the apolipoprotein A-I gene revealed that most likely the cutting site at the 5'-end of the normally seen 673 bp fragment is lost giving rise to the observed 719 bp Msp I fragment. Based on analyses of 136 DNAs of healthy and non-related caucasians the allelic frequency was determined to be 0.06. The observed Msp I genotype frequencies are in Hardy Weinberg equilibrium. PMID- 2885392 TI - Experiences in relation to drugs/driving offences. PMID- 2885393 TI - Recurrence of duodenal ulcer--an endoscopic study. PMID- 2885390 TI - Initial events in the formation of immune deposits in passive Heymann nephritis. gp330-anti-gp330 immune complexes form in epithelial coated pits and rapidly become attached to the glomerular basement membrane. AB - The nephritogenic antigen of Heymann's nephritis (HN), gp330, was previously demonstrated (4-9) to be a resident glycoprotein of coated pits in the glomerular and proximal tubule epithelium of rats, and anti-gp330 IgG given intravenously was found to form IDs in glomeruli (passive HN). The purpose of this study was to investigate the detailed events that occur in the formation of IDs in passive HN. HN was induced by the injection of either 125I-labeled or unlabeled anti-gp330 IgG. At various times after injection (15 min to 8 d) the kidneys of some of the injected rats were fixed by perfusion, and the distribution of the rabbit IgG was determined by immunofluorescence and by immunoelectron microscopy. Glomeruli were isolated from the kidneys of injected rats and used for isolation of GBM fractions or for elution of the bound IgG. At 15 min to 1 h after injection, the rabbit IgG was localized by immunocytochemistry exclusively in coated pits along the podocyte plasmalemma facing the GBM. By 1-8 d, anti-gp330 IgG was detected in larger electron-dense IDs often located under the slit diaphragms. Serial sectioning revealed that each of the IDs maintained contact with a coated pit at some level. When GBMs isolated from rats given radiolabeled anti-gp330 IgG were examined by electron microscopy, the IDs were found to remain attached to the GBMs as early as 15 min after injection and coisolated with them at all time points. By double-immunolabeling of the isolated GBMs with two sizes of gold particles, both the antigen (gp330) and the anti-gp330 IgG could be demonstrated in IDs at all time points. When the amount of radiolabeled anti-gp330 bound to GBM fractions was compared with that of isolated glomeruli, it was found that 20% of the radiolabel remained bound to the purified GBMs at 15 min after injection, and 90% at 3 d. The bound IgG was released only by treatments that disrupt antibody-antigen complexes (high and low pH), but not by the other treatments we tried (detergent, high salt, heparinase, or collagenase digestion). When the IgG bound to glomeruli was eluted with acid citrate buffer 3 d after injection, it was found to specifically immunoprecipitate only gp330 from detergent-solubilized 125I-labeled kidney microvillar vesicles. By isoelectric focusing the eluate was found to be enriched in IgGs with acidic isoelectric points.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2885394 TI - Role of T lymphocyte subsets in protection and recovery from Hantaan virus infection in mice. AB - Adult athymic nude (BALB/c background) mice or inbred BALB/c mice were inoculated intraperitoneally with Hantaan virus (HV), and attempts were made to isolate the virus from brain, lung and spleen. Virus was isolated from the organs of BALB/c mice for only a short time after infection but was isolated from various organs of nude mice consistently for at least 84 days after infection. Viral antigen was also detected in various organs of nude mice for a long time after infection. The effects of adoptive transfer of immune serum or immune T cells from BALB/c to nude mice before or after virus inoculation were examined. Before transfer, the T cell fraction was treated with complement (C') (group 1), anti-L3T4 + C' (group 2), anti-Lyt1.2 + C' (group 3) or anti-Lyt2.2 + C' (group 4). When transferred before virus inoculation to test the effects on protection against infection, immune serum and T cells of groups 1, 2 and 4 were effective. When transferred after HV inoculation to test the effects on clearance of virus, group 1 was the most effective followed by group 2. These results suggest that humoral and cellular immunity both have roles in protection against HV infection, and that T cells possessing L3T4- Lyt2+ markers on the cell-surface are especially important for elimination of infectious virus in vivo. PMID- 2885395 TI - Presynaptic modulation by octopamine at a single neuromuscular junction in the mealworm (Tenebrio molitor). AB - The effect of octopamine on the neuromuscular junction of the mealworm (Tenebrio molitor) was examined. Octopamine potentiated excitatory junctional potentials (EJPs) recorded intracellularly and extracellularly from ventral longitudinal muscle fibers. The potentiating action of octopamine was blocked in the presence of the alpha-adrenergic blocking agent, phentolamine, but not in the presence of another alpha-blocker, phenoxybenzamine, or the beta-blockers propranolol and dichloroisoproterenol. The resting membrane potential, membrane input resistance, reversal potential of EJP, glutamate potentials, and spontaneous miniature EJPs were found to be unaffected by octopamine. In contrast, quantal contents estimated by the extracellularly recorded EJP failures were greatly increased by octopamine. These results suggest that octopamine acted on the presynaptic terminals via alpha-adrenoceptor-like receptors (octopamine receptors) at the Tenebrio neuromuscular junctions to enhance the transmitter release associated with the motor nerve impulses. PMID- 2885396 TI - Ion dependence of neurotransmitter uptake: inhibitory effects of ion substitutes. AB - Several ions commonly used as substitutes for Na+ or Cl- were found to inhibit directly the high-affinity uptake of norepinephrine, dopamine, serotonin, and gamma-aminobutyric acid, but not glutamate or glutamine. When Na+ was partially replaced by any of several different cations or sucrose the uptake of all neurotransmitters studied except that of serotonin was reduced more than could be accounted for by just the inhibitory effect of the cation substitute. In contrast, when Cl- was partially replaced by any of several anions only the uptake of dopamine was reduced more than could be accounted for by the inhibitory effect of the anion substitute. These results suggest that for most neurotransmitters the electrochemical potential for Na+, but not for Cl-, contributes to the uptake driving force. When either Na+ or Cl- was totally replaced by an ion substitute or by sucrose the high-affinity uptake was virtually abolished, an exception being that glutamate uptake was not affected when isethionate was substituted for Cl-. The lack of uptake in the absence of either Na+ or Cl- may reflect a specific role for these ions in either increasing the affinity between the substrate and the carrier, or facilitating the translocation process. Alternatively, the transport carriers may undergo a nonspecific conformational change to an inactive form in the absence of Na+ or Cl . A partial substitution of Na+ with Li+ or sucrose differentially affected the kinetics of uptake in that replacement with Li+, but not sucrose, usually resulted in a marked increase in the Km values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885397 TI - Phosphorylation characteristics of brain clathrin-coated vesicle endogenous proteins. AB - Clathrin-coated vesicles purified from bovine brain express protein kinase activity on two principal endogenous vesicle-associated substrates: a 50,000-Mr polypeptide (pp50) and clathrin-associated protein2 (CAP2; the faster-migrating clathrin light chain). Various exogenous substrates, e.g., casein, phosvitin, histone II, and histone III, also are phosphorylated. The pp50 protein kinase activity of clathrin-coated vesicles is not modulated by Ca2+, calmodulin, phosphatidylserine, or cyclic AMP. On the other hand, phosphorylation of the other endogenous substrates requires certain activators, including histone, polylysine, polyarginine, or polyethylenimine. Phosphate incorporation into pp50 was sensitive to divalent cations that inhibit sulfhydryl-dependent enzymes in the following order of potency: Zn2+ greater than Hg2+ greater than Cd2+, Cu2+, and Pb2+. Phosphate incorporation into CAP2 with polylysine present was insensitive to divalent cations. The alkylating agents dithiodinitrobenzene, phenacyl bromide, and N-ethylmaleimide inhibited phosphate incorporation into pp50 up to 90% without affecting incorporation into the other substrates. Vanadium pentoxide inhibited phosphorylation of CAP2 but had a minimal effect on pp50. CAP2 kinase activity was separated from the coated vesicle membrane and from dis-assembled clathrin triskelions, coeluting with the assembly polypeptide complex on a Sepharose 4B column. It retained phosphorylation properties similar to those of intact vesicles. These data imply that clathrin-coated vesicle kinases are elements of the coat proteins and may be involved in the assembly/disassembly of clathrin triskelions or interactions of coated vesicles with other cellular components. PMID- 2885398 TI - Glutamine synthetase of the human brain: purification and characterization. AB - Glutamine synthetase (GS) isolated from human brain formed a single band on sodium dodecyl sulfate-polyacrylamide gel with a molecular weight of 44,000. The enzyme had a specific activity of 179.2 U/mg protein when assayed by measuring the rate of the formation of gamma-glutamylhydroxamate using hydroxylamine as a substrate. In the presence of manganese ions, the relative activity of human brain GS was much lower than that of the sheep brain enzyme. The suppression of activity by increasing the ADP concentration, however, was less marked in the human enzyme than that in the sheep enzyme. Antibodies were raised in rabbits against the purified enzyme. The double-immunodiffusion technique disclosed cross reactivities among GSs isolated from human, sheep, and rat brains, but the enzymes were not immunologically identical. Immunohistochemically, GS was localized in the cytoplasm of astrocytes in the human and rat brains and in pericentral hepatocytes of the liver. PMID- 2885399 TI - Control of Thy-1 glycoprotein expression in cultures of PC12 cells. AB - The effects of nerve growth factor (NGF) and cholera toxin on the expression of the Thy-1 glycoprotein were examined in cultures of naive and primed PC12 cells using an enzyme-linked immunoadsorbent assay (ELISA). With primed PC12 cells, NGF induced a rapid increase in Thy-1 expression over a time course similar to that of neurite regeneration, with half-maximal and maximal increases apparent at 0.6 and 6 ng/ml NGF. Cholera toxin and dibutyryl cyclic AMP, but not B-cholera toxin or antibodies to the toxin receptor, were found to inhibit NGF-induced increases in Thy-1. Morphological differentiation of naive PC12 cells induced by NGF, but not cholera toxin, was also associated with increased expression of Thy-1. Despite showing a synergistic effect on morphological differentiation, cholera toxin was again found to inhibit NGF-induced increases in Thy-1 expression in cultures of naive PC12 cells. These data suggest that agents that interact directly or indirectly with adenylate cyclase may regulate the responsiveness of PC12 cells to NGF, and as such modulate the expression of the Thy-1 glycoprotein. PMID- 2885400 TI - Taxol and derivatives: a biogenetic hypothesis. AB - Based on the structural differences of compounds isolated from various species of Taxus, this brief review suggests a biogenetic approach to taxol. This hypothesis could be of some help in the synthesis of this complex molecule exhibiting significant antitumor properties. PMID- 2885401 TI - Alpha-2 receptor blockade increases responsiveness of locus coeruleus neurons to excitatory stimulation. AB - This study presents evidence that alpha 2-receptors in the locus coeruleus (LC) regulate the responsiveness of LC neurons to excitatory stimuli. In the first experiment, intravenous administration of the alpha 2-adrenergic antagonist idazoxan markedly potentiated the responses of LC neurons to the excitatory stimulus of contralateral hind paw compression (PC). Increased responsiveness of LC neurons to PC was seen with doses of idazoxan far below those that altered spontaneous activity of the LC. In the second experiment, increased responsiveness of LC neurons to PC was seen when low doses of idazoxan were infused directly into the LC, thereby indicating that increased responsiveness of LC neurons resulted from blockade of alpha 2-receptors in the LC region and not from greater stimulus input to the LC resulting from blockade of alpha 2 receptors elsewhere. In the third experiment, another alpha 2-adrenergic antagonist, yohimbine, also increased the responsiveness of LC neurons to PC. Finally, the response of the LC to another excitatory stimulus, peripheral injection of nicotine, was also found to be increased by idazoxan. Results obtained prior to these studies had indicated that alpha 2-receptors in the LC regulate the period of quiescence that follows a burst of LC firing. However, more recent studies suggest that this quiescence results primarily from changes in ionic conductance of the membrane following directly from depolarization. The present findings indicate that, in addition to whatever role alpha 2-receptors play in regulating postfiring quiescence, these receptors in the LC appear to play a major role in regulating the responsiveness of LC neurons to excitational influences. PMID- 2885402 TI - Activation of immunoregulatory lymphocytes obtained from patients with malignant gliomas. AB - The responsiveness of T cells and their subsets (T-helper cells and T-suppressor cells) obtained from patients with malignant gliomas was evaluated in an effort to further define the mechanism of their impaired host immunocompetence. This study demonstrates that peripheral blood lymphocytes obtained from these patients have impaired responsiveness to a variety of mitogens including phytohemagglutinin, concanavalin A, pokeweed mitogen, and anti-T3 monoclonal antibody. The impaired lymphocyte responsiveness does not result from the inability of these cells to express receptors for a specific mitogen or antibody. The mitogenic responsiveness of purified T cells is markedly reduced when compared to values obtained from control subjects. Therefore, the decreased T cell reactivity of patients with malignant gliomas does not result simply from a diminution in the absolute number of potentially responding lymphocytes. The mitogen reactivity of the T cell subsets, CD4+ helper cells, and CD8+ cytotoxic/suppressor cells was also investigated. These results demonstrate that the responsiveness of the CD4+ T-helper cell subset obtained from these patients is consistently diminished as compared to control values. In contrast, the reactivity of the CD8+ T cell subset was not nearly as dramatically impaired. Thus, these results indicate that the proliferative defect observed in T cells obtained from patients is located predominantly in the T-helper cell subset. Functional deficiencies in this important subpopulation of T lymphocytes may explain, in part, the presence of depressed immune responsiveness in patients with malignant glial tumors. PMID- 2885403 TI - Association of an apolipoprotein CII allele with familial dementia of the Alzheimer type. AB - In order to identify the genetic locus responsible for familial dementia of the Alzheimer type (DAT), we are studying 10 families in which DAT appears to be inherited as an autosomal dominant trait. Genotypes for a TaqI restriction fragment length polymorphism (RFLP) at the apolipoprotein CII locus were determined for the following groups: affected and unaffected DAT family members, DAT subjects with no family history of the disease, and normal control subjects. The control group included 103 individuals from our study and 123 from the study of Wallis et al. (Hum. Genet., 68 (1984) 286). The frequency of the TaqI fast (F) allele in the affected familial DAT subjects (0.64 +/- 0.08) differed significantly from that for the control group (0.39 +/- 0.02) (Z = 2.87, P less than 0.005). In contrast, the F-allele frequency for the unaffected family members was 0.31 +/- 0.09, which was similar to that of the combined control group (Z = 0.78, P greater than 0.40). Subsequently, genotypes were determined for two other polymorphisms at the Apo CII locus: a BanI RFLP and a BglI RFLP. For these two polymorphisms, the allele frequencies for the familial DAT subjects differed from the unaffected control groups but the differences were smaller and not statistically significant. These data suggest a previously unrecognized association between the Apo CII TaqI F-allele and familial DAT. PMID- 2885404 TI - Infection of Aotus vociferans (karyotype V) monkeys with different strains of Plasmodium vivax. AB - Twenty splenectomized Aotus vociferans (karyotype V) monkeys were infected with strains of Plasmodium vivax from New Guinea, North Korea, Indonesia, El Salvador, and Honduras. Peak parasite densities ranged from 4,840 to 75,500 per mm3. Gametocytes infective to different species of mosquitoes were produced with all strains of P. vivax studied. Two transmissions of the Chesson strain of P. vivax were made by the intravenous inoculation of dissected sporozoites from An. dirus mosquitoes. Prepatent periods were 16 days. PMID- 2885405 TI - Actions of the alpha-1 adrenoceptor blocker bunazosin on the norepinephrine induced contraction of smooth muscles in the rabbit proximal urethra. AB - Effects of bunazosin on the norepinephrine-induced electrical and mechanical activities of smooth muscles of the rabbit proximal urethra were investigated using microelectrode and tension recording methods. Responses to norepinephrine were mediated by activation of both alpha-1 and beta adrenoceptors. In the presence of propranolol, the norepinephrine-induced contraction increased and, with yohimbine, the phasic but not tonic contraction was only inhibited slightly. Contributions of the alpha-2 adrenoceptor to the norepinephrine-induced contraction were negligible. Bunazosin inhibited in a concentration-dependent manner both the phasic and tonic responses of the norepinephrine-induced contraction, and the concentration-response relationship for norepinephrine shifted to the right. The Schild plot obtained from measurements of tonic responses in this antagonism yielded a straight line with a slope of 0.96. The pA2 value for bunazosin was 8.39 and the KB value was 4.1 nM. Prazosin had similar effects (the corresponding values being 0.96, 8.21 and 6.2 nM, respectively). The mechanical response evoked by field stimulation was composed of cholinergic, noradrenergic alpha-1 and noncholinergic-nonadrenergic contractions and of a subsequent nonadrenergic-noncholinergic relaxation. Bunazosin inhibited the twitch contraction evoked by field stimulation more than did prazosin, albeit not completely. These results indicate that although the smooth muscle tone in the urethra is regulated by multiple neural factors, the elevation of the tone is regulated predominantly by activation of the alpha-1 adrenoceptors. Bunazosin has an antagonistic action on this receptor. The actions of bunazosin are discussed in relation to the clinical application in cases of inadequate micturition. PMID- 2885406 TI - Pharmacological evidence for alpha-2 adrenoceptor heterogeneity: differential binding properties of [3H]rauwolscine and [3H]idazoxan in rat brain. AB - In the preceding paper, we have reported that the two alpha-2 adrenoceptor antagonists, [3H]rauwolscine and [3H]idazoxan, exhibit markedly different autoradiographic distributions throughout rat brain. Although [3H]idazoxan labeling appears over brain regions receiving noradrenergic innervation, [3H]rauwolscine binding sites are localized most densely in several areas corresponding to dopaminergic terminal fields. We have presently characterized the pharmacological binding properties of high affinity [3H]rauwolscine and [3H]idazoxan labeled sites, using tissue preparation and incubation protocols which are identical to those used in the previous autoradiographic study. Endogenous monoamines inhibited radioligand binding with a rank order of potency of epinephrine = norepinephrine greater than dopamine greater than serotonin. Numerous dopaminergic compounds failed to inhibit either [3H]rauwolscine or [3H]idazoxan binding with high potency, and rauwolscine was a poor inhibitor of [3H]spiroperidol binding. Several adrenergic compounds which selectively label alpha-1 or beta adrenoceptors also exhibited low potency in inhibiting either radioligand. In contrast, alpha-2 adrenoceptor agonists and antagonists possessed high affinity for both [3H]rauwolscine and [3H]idazoxan labeled sites. Their relative potencies at the two sites differed, however. Whereas idazoxan was equipotent in inhibiting either [3H]rauwolscine or [3H]idazoxan binding, rauwolscine exhibited 10-fold higher affinity for its own labeled site. These pharmacological data are consistent with anatomical data presented in the preceding paper, which support the existence of a heterogenous population of alpha-2 adrenoceptors within rat brain, labeled entirely by [3H]idazoxan and only in part by [3H]rauwolscine. PMID- 2885408 TI - Amphetamine-like effects of anorectics and related compounds in pigeons. AB - Four pigeons were trained to discriminate injections of d-amphetamine (AMPH; 2.0 mg/kg i.m.) from saline with responding maintained under a fixed-ratio 30 schedule of food delivery. When drugs used therapeutically as anorectics were tested, they consistently produced greater than 80% of AMPH-appropriate responding. The order of potency for substituting for AMPH was: mazindol greater than AMPH = phenmetrazine = phentermine greater than chlorphentermine = phendimetrazine = diethylpropion greater than clortermine = mefenorex. Other anorectics such as phenylpropanolamine (0.3-30.0 mg/kg) and fenfluramine (1.0 17.0 mg/kg) only substituted partially for AMPH whereas benzphetamine (1.0-100.0 mg/kg) resulted primarily in saline-appropriate responding. Compounds related to AMPH in biochemical mechanism of action or psychomotor stimulant activity also were tested. Methylphenidate (0.1-3.0 mg/kg), piribedil (0.3-17.0 mg/kg) and nisoxetine (0.03-1.0 mg/kg) shared discriminative stimulus properties with AMPH whereas bupropion (1.0-30.0 mg/kg) and propylhexedrine (10.0-100.0 mg/kg) substituted for AMPH in two of three pigeons tested. In contrast, caffeine and fenetylline resulted principally in saline-appropriate responding. Compounds from pharmacological classes not related to AMPH, such as morphine, diazepam and phencyclidine, failed to substitute for AMPH. In general, compounds with anorectic and/or stimulant properties shared discriminative stimulus properties with AMPH. PMID- 2885407 TI - Interaction of beta adrenergic agonists and antagonists with brain beta adrenergic receptors in vivo. AB - There is interest in knowing whether beta adrenergic antagonists or agonists, when administered systemically, can enter the brain to interact with central beta adrenergic receptors. To study this, the reduction in the radioactive content in the brain of rats after administration of (-)-[125I]iodopindolol (IPIN) by systemically administered beta agonists or antagonists was measured. Previous studies show that after the i.v. administration of IPIN the binding in vivo to various areas of the central nervous system has the characteristics expected of binding to beta adrenergic receptors. Of the antagonists tested, pindolol and butylpindolol showed potent interactions with beta receptors in both cortex and cerebellum whereas atenolol and practolol did not interact at doses up to 30 mg/kg. CGP-12177 showed moderate potency in inhibiting IPIN binding in vivo. We have shown previously that propranolol and alprenolol inhibit IPIN binding with high potency in cortex and cerebellum. At high doses, butoxamine, a beta-2 antagonist, reduced the binding of IPIN in the cerebellum but not in the cortex. Of the agonists tested, clenbuterol and prenalterol caused a significant dose dependent reduction of the binding of IPIN, with clenbuterol being more potent. Isoproterenol, salbutamol, salmefamol and dobutamine had no effect. With the exception of CGP-12177, the affinity of the drugs for central beta adrenergic receptors measured in vitro was correlated significantly with their ability to inhibit IPIN binding in vivo whereas their degree of lipophilicity was not correlated significantly with potency in vivo. The inhibition of IPIN binding in vivo from brain areas can be used to evaluate whether drugs penetrate into brain and interact with central beta adrenergic receptors. PMID- 2885409 TI - Glucagon's chronotropic action is calcium dependent. AB - Evidence is increasing that many anesthetics and cardiovascular agents alter cellular Ca kinetics and flux. In prior work we demonstrated that the tachycardic effects of glucagon were significantly blunted by Ca channel blockade, but not by beta adrenergic receptor blockade. Thus, the chronotropic effects of glucagon may be dependent upon extracellular Ca levels. Based upon these observations, we tested the hypothesis that changes in circulating ionized Ca concentrations may alter glucagon's ability to increase heart rate in rats. In conscious normocalcemic rats, glucagon's tachycardic actions were dose related with peak effects obtained at 1 to 2 min and persisting approximately 10 min after 1.0 mg/kg of glucagon. The effects of altered Ca levels on glucagon tachycardia were evaluated in three groups of rats: 1) rats rendered hypercalcemic by the infusion of Ca chloride (10, 50 or 100 mg/ml/hr); 2) rats rendered hypocalcemic by infusion of the Ca chelator EDTA (15 or 30 mg/ml/hr); and 3) normocalcemic rats infused with saline. Normocalcemic rats had a mean ionized Ca level of 4.73 mg/dl. In rats, increasing Ca chloride doses resulted in increasing mean serum ionized Ca levels (5.24, 8.35 and 15.2 mg/dl, respectively), whereas increasing doses of EDTA produced progressive decreases in mean ionized Ca (3.62 and 2.13 mg/dl, respectively). Severe hypo (2.13 mg/dl)- or hypercalcemia (15.2 mg/dl) significantly blunted glucagon's chronotropic action (51 and 44%, respectively). From these data, we conclude that glucagon has its maximal tachycardic action at physiologic Ca levels (being blunted by both hyper- and hypocalcemia), indicating that this effect of glucagon is Ca dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885410 TI - Differential effects of nifedipine, nicorandil and nitroglycerin on the pressor responses elicited by selective alpha-1 and alpha-adrenoceptor agonists in conscious dogs. AB - The influence of vasodilators with varying mechanisms of action on pressor responses mediated by alpha-1 and alpha-2 adrenoceptors was investigated in chronically instrumented, conscious dogs. After ganglionic, cholinergic and beta adrenergic blockade, equipressor doses of phenylephrine (0.6 microgram/kg i.v.), a selective alpha-1 adrenoceptor agonist, and B-HT 933 (20 micrograms/kg i.v.) a selective alpha-2 adrenoceptor agonist, were administered before and in the presence of infusions of nifedipine (0.25-2.0 micrograms/kg/min), nicorandil (4.0 32.0 micrograms/kg/min) or nitroglycerin (1.0-8.0 micrograms/kg/min). Nifedipine produced a dose-related attenuation of the increase in mean arterial pressure after bolus administration of phenylephrine (from 26 +/- 1 to 7 +/- 1 mm Hg) and B-HT 933 (from 29 +/- 2 to 5 +/- 1 mm Hg). Nicorandil did not affect phenylephrine-mediated pressor responses but significantly attenuated those to B HT 933 (28 +/- 2 to 10 +/- 1 mm Hg). In contrast, nitroglycerin had no effect on either phenylephrine or B-HT 933-mediated responses. In additional experiments after autonomic nervous system blockade, multiple doses of phenylephrine (0.6, 1.25 and 2.5 micrograms/kg i.v.) and B-HT 933 (10, 20 and 40 micrograms/kg i.v.) were administered before and after i.v. infusions of nifedipine (1.0 microgram/kg/min) or nicorandil (16.0 micrograms/kg/min). Nifedipine significantly decreased the pressor responses to all doses of phenylephrine and B HT 933. In contrast, the attenuation from control of alpha-2-mediated increases in arterial pressure by nicorandil was partially overcome at higher doses (40 micrograms/kg) of B-HT 933.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885411 TI - Role of the alpha agonist activity of dobutamine in mediating cardiac output: effects of prolonged isoproterenol infusion. AB - Hemodynamic activities of dobutamine enantiomers were studied in either control rats or those infused with isoproterenol (400 micrograms/kg/hr) for 4 days. In control animals prazosin attenuated the effects of (+/-)-dobutamine on cardiac output by approximately 50%; remaining activity was blocked by propranolol. After isoproterenol infusion (+/-)-dobutamine was less efficacious and the blocking effects of prazosin were greater than 90%. Isoproterenol infusion had no effect on (-)-dobutamine-mediated (alpha-1 adrenoceptor agonist) increases in cardiac output and these actions were blocked by prazosin. By contrast, compared to (+/-) and (-)-dobutamine, effects of (+)-dobutamine (beta adrenoceptor agonist) on cardiac output were modest, not altered by prazosin and were blocked by propranolol; (+)-dobutamine was inactive after isoproterenol infusion. (-) Dobutamine increased systemic vascular resistance in both control and isoproterenol infused rats, whereas (+)-dobutamine was inactive. (+/-)-Dobutamine increased systemic vascular resistance only in isoproterenol-infused rats. All increases in systemic vascular resistance were blocked by prazosin. Neither (+/-) nor (+)-dobutamine significantly altered stroke volume. By contrast, (-) dobutamine resulted in prazosin-sensitive increases in stroke volume in both control and isoproterenol-infused rats. In control animals, (+/-)-, (+)- and (-) dobutamine increased heart rate in a dose-dependent manner; chronotropic effects of (-)-dobutamine were less than those of either (+/-)- or (+)-dobutamine. Chronotropic effects were not demonstrable in isoproterenol-infused animals. These data support the notion that in control rats cardiac output may be increased by either alpha or beta adrenoceptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885412 TI - Alpha-1 adrenergic receptor binding in aortas from rat and dog: comparison of [3H]prazosin and beta-iodo-[125I]-4-hydroxyphenyl-ethyl-aminomethyl-tetralone. AB - We have identified and characterized pharmacologically alpha-1 adrenergic receptors in aorta from dog and rat utilizing two alpha-1 antagonists, [3H]prazosin and beta-3-iodo[125I]-4-hydroxyphenyl-ethyl-aminoethyl-tetralone [125I]HEAT, to determine receptor number and affinity. The rat and dog alpha-1 receptors were found to be very similar. In the dog, KD values were 27 and 11 pM for [3H]prazosin and [125I]HEAT, respectively, whereas maximum binding values were 89 and 65 fmol/mg of protein. KD values in rat aorta were 22 and 15 pM for [3H]prazosin and [125I]HEAT, respectively, whereas maximum binding values were 62 and 47 fmol/mg of protein. Both tissues demonstrated a rank order potency of antagonist inhibition of the two radioligands consistent with an alpha-1 adrenergic receptor with prazosin greater than phentolamine greater than yohimbine. A comparison between IC50 values for both the ligands and the tissues shows strong correlations suggesting the two radioligands are identifying a similar receptor population and that the receptor labeled by the ligands has similar pharmacologic characteristics in the two tissues. PMID- 2885413 TI - Alpha-2 receptors mediate an endogenous noradrenergic suppression of kindling development. AB - We sought to elucidate the receptor subtype through which endogenous norepinephrine suppresses epileptogenesis in the rat kindling model. To this end we examined the effects of systemically administered selective antagonists and an alpha-2 agonist on kindling development and on kindled seizures. The alpha-2 adrenergic antagonists idazoxan, yohimbine and rauwolscine (0.1-10.0 mg/kg i.p.) dose-dependently facilitated amygdala kindling development. Central administration of idazoxan (20 micrograms/40 microliter i.c.v.) produced an equivalent facilitation. The facilitation was selective for alpha-2 antagonists because neither the alpha-1 antagonist corynanthine (0.1-10.0 mg/kg i.p.), nor the beta antagonist propranolol (0.1-10.0 mg/kg i.p.), nor the selective beta-1 antagonist ICI 89,406 (10 micrograms/40 microliter i.c.v.) nor the beta-2 antagonist ICI 118,551 (0.5-5.0 mg/kg i.p.) modified kindling development. The alpha-2 agonist clonidine (0.01-0.2 mg/kg i.p.) dose-dependently suppressed kindling development. In contrast to the effects on kindling development, neither the alpha-2 antagonists nor clonidine modified seizures elicited from previously kindled animals. We interpret the data to indicate that endogenous norepinephrine suppresses kindling development by activation of postsynaptic alpha-2 receptors. The selective inhibition of kindling development, but not kindled seizures, suggests that alpha-2 agonists may be effective antiepileptogenic, but not anticonvulsant, agents. PMID- 2885414 TI - Role of endogenous histamine in postanaphylactic phase of allergic inflammation in rats. AB - Role of endogenous histamine in postanaphylactic phase of allergic inflammation was examined by using a rat model of allergic inflammation of air pouch type. Histamine in the exudate revealed a biphasic increase. The anaphylactic increase was followed by rapid decrease and then by a gradual rising in postanaphylactic phase with the maximum attained around 24 hr after the antigenic challenge. It again decreased gradually. The histamine increase in the postanaphylactic phase was accompanied by the increase of histidine decarboxylase activity in inflammatory tissues. Local administration of pyrilamine, an H1 antagonist, together with either methysergide, a serotonin antagonist, or cimetidine, an H2 antagonist, was unable to inhibit vascular permeability response in the postanaphylactic phase. When histaminase was administered locally in the postanaphylactic phase to reduce histamine in the exudate, neutrophil accumulation in the exudate was enhanced without any change in exudate accumulation. Enhancement of the neutrophil accumulation was also inducible with local administration of cimetidine but not with pyrilamine. Local administration of histamine inhibited the neutrophil accumulation dose-dependently. These results suggest that endogenous histamine released in the postanaphylactic phase contributes to downward regulation of neutrophil accumulation in the inflammatory site without affecting the vascular permeability. PMID- 2885416 TI - Zwitterionic analogues of cimetidine as H2 receptor antagonists. AB - A series of analogues of the H2 receptor histamine antagonist cimetidine have been synthesized in which the dipolar cyanoguanidine group has been replaced by a number of zwitterionic moieties. Although none of the compounds is more effective than cimetidine in blocking histamine-stimulated tachycardia on the isolated guinea pig atrium, the activities of most of the compounds possessing rigid dipoles can be accounted for on the basis of dipole orientation relative to the common side chain and by considering the active species in each case to be the zwitterion. These findings are in general agreement with those found for analogues having conjugated groups as dipoles. PMID- 2885415 TI - Effects of auranofin and other antirheumatic drugs on human myelopoiesis in vitro. AB - Leukopenia is one of the more serious side effects of auranofin (AF) therapy for rheumatoid arthritis. AF and its deacetylated form inhibited the development of macrophage and granulocytic colonies from progenitor cells in human bone marrow even at concentrations less than or equal to 10(-9)M. The disease suppressive activity of AF could result in part from the reduction of cell numbers in arthritic lesions and our findings provide a mechanism for this possibility. In contrast, other slow acting antirheumatic drugs, sulfasalazine, chloroquine and hydroxychloroquine, show partial inhibition of colony development but at concentrations of the order of 10(-5)M. PMID- 2885417 TI - Solid-phase synthesis and biological properties of psi [CH2NH] pseudopeptide analogues of a highly potent somatostatin octapeptide. AB - A series of psi [CH2NH] pseudopeptide analogues of a potent somatostatin octapeptide analogue, H-D-Phe-Cys-Try-D-Trp-Lys-Val-Cys-Thr-NH2, were synthesized by using a newly developed solid-phase method for direct introduction of the CH2NH peptide bond isostere. Analogues were obtained in normal yields via a combination of sodium cyanoborohydride mediated reductive alkylation of resin bound peptide amine with a tert-butoxycarbonyl amino acid aldehyde for introduction of a CH2NH bond and normal solid-phase peptide chemistry. A racemization test on a model pseudodipeptide indicated that no more than 6% racemization took place during the aldehyde preparation and alkylation steps. Analogues were examined for their ability to inhibit growth hormone release in vivo in sodium pentobarbital anesthetized rats and in vitro from cultured rat anterior pituitary cells. Analogues modified at the amide carbonyl of Cys2 and Lys5 showed the highest in vivo activity (20 and 8 times more potent than SRIF, respectively) and in vitro activity (0.17 and 0.67 times as active as SRIF). This compared to in vivo and in vitro potencies of 8000% and 100%, respectively, for the parent analogue. Modification of the other cyclic ring amide carbonyls of Tyr3, D-Trp4, and Val6 or the N- or C-terminal amide carbonyl of D-Phe1 or Cys7 gave analogues with considerably lower in vitro or in vivo potencies. The results appear to offer support for a proposed type II beta-turn solution conformation centered on the D-Trp-Lys portion of SRIF octapeptide analogues, resulting in possible hydrogen-bonding interactions between Tyr3 and Val6 and D-Phe1 and Thr8 residues in the parent peptide. These would then be disrupted by methylene replacement of the carbonyl groups with concomitant loss of biological activity as was observed. PMID- 2885418 TI - Structure-activity relationships among di- and tetramine disulfides related to benextramine. AB - The synthesis and irreversible alpha-blocking activity in the rat vas deferens of a series of tetra- and diamine disulfides 2-38, structural analogues of benextramine (BHC), are described. All compounds containing a central cystamine moiety displayed an irreversible alpha-adrenergic blockade at concentrations ranging from 10(-4) to 6 X 10(-6)M. Potency was increased in cystamines N,N' disubstituted with 6-aminohexyl groups, especially when the outer nitrogen atoms bear arylalkyl substituents or are enclosed in a ring. However, N,N,N',N' tetrasubstituted cystamines were poor blockers. Structural specificity in the outer portion of the tetramine disulfide is low, since many types of substituents gave rise to potent alpha-blockers. Even replacement of the outer amines with nonbasic ethers or amides was observed to maintain irreversible alpha-blockade. PMID- 2885419 TI - Design of nonpeptidal ligands for a peptide receptor: cholecystokinin antagonists. AB - A series of 3-substituted 5-phenyl-1,4-benzodiazepines, nonpeptidal antagonists of the peptide hormone cholecystokinin (CCK), have been synthesized. Designed on the basis of facts regarding CCK, its natural-product antagonist asperlicin (3), and the antianxiety agent diazepam (4), these compounds represent a significant departure from existing CCK antagonists. They also constitute perhaps the first examples of simple, nonpeptidal ligands for a peptide receptor to arise by design rather than by screening. These compounds serve to illuminate the distinction between central and peripheral CCK receptors, as well as to provide orally effective CCK antagonists of potential pharmacological or therapeutic utility. One rationale for their receptor affinity has possible applications in the design of nonpeptidal ligands for other receptors, peptidal as well as nonpeptidal. PMID- 2885420 TI - Recruitment and retention of minority students in a physician assistant program. AB - The authors report two years of experience in the recruitment and retention of minority physician assistant students and the employment patterns of graduates from one physician assistant program. Recruitment strategies increased the proportion of minority students to 54 percent in the first year of the program and to 44 percent in the second year. The number of years of postsecondary education and clinical experience acquired by the minority students before admission to the program tended to have less impact on their performance in training than did their prior completion of formal academic degree programs and prior level of clinical responsibility. Attrition was higher for the minority students than nonminority students, and the minority students took longer than nonminority students to complete the program. The rates at which the students passed the certifying examination of the National Commission on Certification of Physician's Assistants were comparable for the two groups. Minority graduates tended to practice in areas of health manpower shortage. PMID- 2885421 TI - Survey of graduates of a physician assistant internship concerning practice characteristics and adequacy of training. PMID- 2885422 TI - Successful management of the pediatric examination. PMID- 2885423 TI - Detection of thyroid-stimulating antibodies in sera of patients with Graves' disease--clinical and experimental studies. PMID- 2885425 TI - Neuropathy and orchialgia in a 40-year-old man. PMID- 2885426 TI - The pulsed dye laser for fragmenting urinary calculi. AB - The properties of a laser which effect stone fragmentation have been studied. The pulsed dye laser emitting at 504 nm. in one microsecond duration pulses appears to be the optimum out of a wide range of parameters tested. The laser is coupled to a 200 micron core fiber; this complete with its cladding has a total diameter of only 0.25 mm. Most calculi are fragmented by a series of pulses of up to 30 mJ. The system is used by firing bursts of pulses with the fiber actually in contact with the stone. The result is a very controlled fragmentation which is particularly suited to use in the confines of the ureter. This modality of treatment utilises less energy than ultrasound or electrohydraulic probes to fragment a stone and the very fine, flexible fiber represents a considerable miniaturization. PMID- 2885424 TI - Intracellular digestion of reovirus particles requires a low pH and is an essential step in the viral infectious cycle. AB - Lysosomotropic drugs such as NH4Cl have been useful for studying the role of low pH in early events in virus infection. NH4Cl blocks the production of infectious progeny virus in mammalian reovirus-infected cells. The inhibitory effect of NH4Cl is mediated by an inhibition of intracellular digestion of reovirus outer capsid proteins. In vitro digestion of viral outer capsid proteins produces infectious partially uncoated particles, called intermediate subviral particles, which are no longer inhibited by the presence of NH4Cl. These results indicate that proteolytic processing of reovirus outer capsid proteins takes place in a low pH compartment of the cell and is an essential step in the viral infectious cycle. PMID- 2885427 TI - An assessment of the pulsed dye laser for fragmenting calculi in the pig ureter. AB - The pulsed dye laser was used to fragment ureteric calculi in 10 pig ureters, compared to electrohydraulic disintegration in six pig ureters. The stones were impacted in the proximal ureter and approached by rigid ureteroscopy. Four ureters did not have stones impacted but had ureteroscopes passed. The stones were fragmented and the particles left to pass spontaneously. The degree of inflammatory reaction was graded at the site of fragmentation as well as in the middle and lower ureter. The degree of inflammation seen at the site of fragmentation was significantly less in the laser group than in the electrohydraulic group (p = 0.0027). It was noted that the degree of inflammation seen in the lower ureter was significantly greater than that seen at the site of fragmentation (p = 0.01), and that this grade of inflammation correlated well with the size of ureteroscope used (p = 0.0026). Further, the degree of dilatation of the ureter and pelvicalyceal system was significantly greater when the larger calibre ureteroscope had been used (p = 0.0056) ranging up to hydronephrosis with flattening of the papillae. If there is any parallel which can be drawn between the pig ureter and the human ureter then it suggests that ureteroscopy is more significant than the modality of fragmentation used. The contribution of the laser may therefore be more by the miniaturization of instrumentation which will be made possible than by any advantage it may have as a fragmenter. PMID- 2885428 TI - Tubule recovery after obstructive nephropathy relief: the value of enzymuria and microproteinuria. AB - The recovery of tubules after relief of obstructive nephropathy may be investigated through serial assessment of the urinary excretion of tubular enzymes alpha-glucosidase, gamma-glutamyl-transferase and N-acetyl glucosaminidase as well as of the microprotein beta-2-microglobulin. We studied 21 patients in whom obstructive nephropathy was relieved by operative or nonoperative methods. Anuria persisted from 2 to 14 days. In these patients urinary excretion of alpha-glucosidase, gamma-glutamyl-transferase, N-acetyl glucosaminidase and beta-2-microglobulin, as well as the serum creatinine were assessed weekly. Serum creatinine was the earliest index to return to normal (within 9 to 26 days). Enzymuria returned to normal within 35 to 45 days, whereas normal urinary excretion of beta-2-microglobulin occurred more than 100 days after relief of obstructive nephropathy. N-acetyl glucosaminidase and gamma glutamyl-transferase proved to be more reliable than alpha-glucosidase in detecting recovery of the luminal membrane of the proximal tubule. The return to normal of urinary beta-2-microglobulin levels has been shown to occur later, since more specific and complex intracellular functions underlie this index. The pathophysiological aspects of recovery of obstructive nephropathy may be considered similar to those observed in ischemic acute renal failure, since in both instances hemodynamic changes are involved. PMID- 2885429 TI - Laparoscopy in the management of the nonpalpable testis. AB - Laparoscopy was performed at operation in 32 patients between 7 and 63 months old (average age 31 months), who had 33 nonpalpable testes. Of the testes 7 (21.2 per cent) were in the inguinal region or just proximal to the internal ring, 5 (15.2 per cent) were in a high intra-abdominal position and 21 (63.6 per cent) were absent. In every instance of a nonpalpable gonad in which a testis was found to be absent at operation the vas and gonadal vessels were observed laparoscopically to exit the inguinal ring or to end blindly just proximal to the internal inguinal ring. A hernia or patent processus vaginalis was not observed in these 21 cases. In every case of an absent testis the contralateral testis was located normally in the scrotum. Furthermore, when a hernia was observed laparoscopically a testis was found on the ipsilateral side at the level of the internal ring or more distally. PMID- 2885430 TI - Vasoactive intestinal polypeptide in relation to penile erection in the cat evoked by pelvic and hypogastric nerve stimulation. AB - The hemodynamics of penile erection were elucidated in the anesthetized cat by studying volumetrically determined erectile responses of the penis and penile blood flow during frequency-graded bilateral stimulation of the pelvic and the hypogastric nerves, selectively or in combination. The study also provided information on possible neurotransmitter mechanisms. The results indicated that the erectile response is mediated by both the pelvic and hypogastric nerves, operating synergistically to evoke a seemingly maximum erection. Optimum erectile responses for either nerve system were obtained at 16 Hz and threshold responses at 0.5 to one Hz. In the presence of atropine, the erectile response to selective stimulation of the pelvic and the hypogastric nerves, respectively, were clearly curtailed, suggesting a cholinergic mechanism to be partly responsible for the diversion of blood from the penile "resistance vessels" to the cavernous bodies, possibly accomplished via the opening of vessels with a shunt-like function. However, the magnitude of the erectile response to combined pelvic and hypogastric nerve stimulation seemed to be surprisingly little affected by muscarinic blockade. Selective stimulations of the pelvic and the hypogastric nerves, respectively, were both found to cause about a five-fold increase in VIP output from the penis, coordinated in time with the local blood flow increase during erection. These data suggest a VIP-ergic neurotransmitter mechanism to be involved in penile erection in the cat, possibly controlling the dilation of the penile arterial "resistance vessels." PMID- 2885432 TI - Failure of buspirone to protect against lorazepam withdrawal symptoms. PMID- 2885431 TI - Interaction of urinary Tamm-Horsfall protein with transitional cells and transitional epithelium. AB - Uropathogenic E. coli that express mannose sensitive adhesins adhere to agglutinated urinary Tamm-Horsfall protein (THP) and to exfoliated transitional epithelial cells coated with THP. Whether THP interacts with the transitional epithelium in vivo and facilitates adhesin mediated attachment of E. coli is not known. Using immunohistochemical techniques we could not identify THP associated with formalin-fixed, paraffin-embedded transitional epithelium from a variety of sites within the urinary tract. However, varying levels of THP associated with the washed exfoliated transitional cells from 10 different subjects were detected by indirect radioimmunoassay methodologies. After in vitro incubation in human urine the mean interaction of THP with the exfoliated transitional cells increased significantly but closely paralleled the mean interaction of THP with exfoliated vaginal and buccal epithelial cells after identical incubation. We conclude that the interaction of THP with transitional cells in vivo is nonspecific and occurs after detachment from the mucosa. THP may act as a natural host defense against E. coli bacteriuria by inhibition of adhesion mediated bacterial adherence to the urothelium. PMID- 2885433 TI - New inotropic drugs for heart failure. PMID- 2885434 TI - [MEN-2, a dominantly inherited neoplasia]. AB - MEN-2 is a syndrome which is characterized by association of medullary thyroid carcinoma with pheochromocytoma. This syndrome is transmitted in an autosomal dominant fashion with very high penetrance. Linkage analysis of the kindreds at high risk and comparison of leukocytes- and tumor-DNAs of the patients using restriction fragment length polymorphisms (RFLPs) will be useful to find out the locus of the gene which predisposes to the syndrome. The environment factors play little role in the tumorigenesis in MEN-2. PMID- 2885435 TI - [Heredity in clinical cancer]. AB - Familial clustering of cancer causes a problem whether significant differences exist from one person to the next in cancer susceptibility. Such clustering could occur simply by the chance occurrence of common environmental exposure, but in rare families, clustering is caused by discrete genetic factors, some being recessive and some being dominant inheritance with mendelian segregation. In this review article, heritable cancers are listed and discussed. Recent laboratory developments, such as the study on chromosome fragile sites and restriction enzyme-fragment length-polymorphism, to find the predisposition for cancer was introduced. Other analysis for individual difference by the genetic epidemiology was also summarized. PMID- 2885436 TI - Regional distribution of sympathetic vasoconstrictor tone in conscious spontaneously hypertensive rats. AB - An electromagnetic flow probe was chronically implanted around the common carotid, superior mesenteric, or renal artery in spontaneously hypertensive rats (SHR). An indwelling catheter was inserted into the terminal aorta for measurement of arterial pressure. Peripheral resistance was calculated by dividing arterial pressure by flow. Decrease in peripheral resistance on ganglion blockade with hexa-methonium bromide was assumed to indicate the presence of vasoconstrictor tone to regional resistance vessels. In the conscious, resting state, peripheral resistance decreased significantly on ganglion blockade in the carotid and renal areas but not in the superior mesenteric area. The magnitudes of the decrease in peripheral resistance in the carotid and renal areas were not greater than the respective, corresponding values in normal rats. Presumably, vasoconstrictor tone in these three vascular regions, being quite different from that in the hindquarters, is not higher in SHR than in normal rats. Venomotor tone does not seem to be elevated in conscious SHR either, because the decrease in the sum of the mean peripheral flows on ganglion blockade, which was assumed to reflect the decrease in cardiac output, was not larger in SHR than in normal rats. Pentobarbital anesthesia did not abolish renal vasoconstrictor tone in SHR as it does in normal rats. PMID- 2885437 TI - Effects of bromocriptine on neuroleptic-induced amenorrhea, galactorrhea and impotence. AB - The effects of bromocriptine on neuroleptic-induced endocrinological disturbances (amenorrhea, galactorrhea and impotence) were investigated. Bromocriptine (5.0 7.5 mg/day) was administered to psychiatric patients receiving neuroleptics and developing hyperprolactinemia. The following results were obtained. Menses recurred in 7 of 10 patients with amenorrhea. A decrease in lactation appeared in 5 of 6 patients with galactorrhea. A significant increase in the serum levels of testosterone was observed after 8 weeks of the treatment in male patients. (N = 6). There was no remarkable deterioration in regard to the psychotic symptoms in schizophrenic patients. (N = 7). In non-schizophrenic patients (N = 9), a significant improvement was observed in regard to "somatic concern" (in Brief Psychiatric Rating Scale). PMID- 2885438 TI - [Moderate ganglioplegia and heparinization in the combined treatment of acute cholecystitis patients]. PMID- 2885440 TI - Cellular mechanisms of action of atrial natriuretic factor. AB - Atrial natriuretic factor (ANF) interacts with its target cells through specific receptors. This interaction induces, in most cell types, the activation of particulate guanylate cyclase and decreased Calcium mobilisation. In addition, ANF also decreases adenylate cyclase activity in some tissues. Activation of particulate guanylate cyclase, and additionally inhibition of adenylate cyclase, appear to initiate the cellular responses to circulating ANF. The activation of particulate guanylate cyclase is tissue-specific, immediate and can be demonstrated also on the solubilized enzyme. The ANF receptor appears to be tightly coupled to particulate guanylate cyclase. The increased formation of cyclic GMP induces cGMP-dependent protein phosphorylation in target cells. In addition, cyclic GMP inhibits Calcium mobilisation in several tissues. This may explain observations of inhibition of Calcium mobilisation after ANF. Cyclic GMP is not only degraded by phosphodiesterase, but is also extruded from target cells. As a consequence of cGMP extrusion, ANF increases the levels of cyclic GMP in plasma and urine in animals and man. Cyclic GMP is also increased in various disease states, in which ANF is increased. In contrast, cyclic AMP plasma levels are unaltered after ANF elevations. At present, the exact mechanisms, by which cellular functions are altered by ANF are still incompletely understood. It is anticipated, that the close correlation between the cyclic GMP system and effects of ANF in various target tissues is a key finding that will help elucidate the exact mechanisms of ANF action. PMID- 2885441 TI - [Hypothalamic hormones and their role in regulating the endocrine system]. PMID- 2885439 TI - Delaying carbohydrate absorption in noninsulin-dependent diabetes mellitus: useful therapy? AB - Epidemiological and psychological studies have revealed major difficulties in motivating diabetic patients to observe a long-term dietary regimen. Therefore, manipulation of intestinal digestion or absorption appears to be a feasible therapeutic approach in the management of diabetes. The addition of natural or chemically processed fiber has been shown to decrease both the postprandial and fasting blood glucose in type-2 diabetics by delaying carbohydrate absorption. Recently, selective enzyme inhibitors of glycoside hydrolases in the upper intestine have been found which create a moderate degree of malabsorption of carbohydrates. The postprandial blood sugar response can be reduced by 50%. However, both these forms of treatment may not be accepted by patients because of impalatability or gastrointestinal side effects. At present only short-term studies with each group of substances are available. Whether the reduction of hyperglycemia is sufficient for the prevention of complications must be clarified in long-term trials. PMID- 2885442 TI - [25th international conference of the Red Cross. A look from inside. 1]. PMID- 2885443 TI - Effects of treatment with prolactin or progesterone on the coincidence of mammary tumors and uterine adenomyosis in young SHN mice. AB - The relative incidence of mammary tumors with uterine adenomyosis was examined in SHN mice subjected to hormonal manipulation between 30 and 90 days of age. The incidence of mammary tumors paralleled that of adenomyosis in controls. A single pituitary grafted under the kidney capsule or progesterone pellet implanted at a young age increased the incidence of both mammary and uterine lesions. However, the pattern of long-term response to hormones was different between mammary gland and uterus. The results indicate the possible relevance of this animal model for study of the cause and management of multiple endocrine syndrome in women. PMID- 2885444 TI - Kinetic analysis of new formation, internalization, and turnover of bristle coated pits of the myeloid sinuses. AB - The rate of new formation of bristle coated pits (BCP) of the myeloid sinuses, their internalization, and turnover was determined by labeling of BCP with bovine albumin adsorbed to colloidal gold (Au) at low temperatures (0 degrees C to 4 degrees C), followed by endothelial activation with balanced saline at 38 degrees C to 40 degrees C for graded periods of time. New formation of BCP was practically instantaneous, occurring within 28 seconds, a time span which includes the in situ assembly of the coating protein clathrin as well as of the material effecting the binding of the ligand. Almost the entire population of BCP was turned over in 6 minutes, a time period which encompasses the initial formation of the plasmalemmal bristle coated binding site to the internalization of BCP. The number of BCP varied within a narrow range indicating a substantial degree of physiological constancy resulting from a quantitative parallelism between internalization and new formation of bristle coated binding sites. The number of BCP is markedly reduced in the prolonged (greater than 12 minutes) absence of endocytosable material. The reduction in the number of BCP is reversible. The binding to BCP at low temperatures (0 degrees C to 4 degrees C) of a series of proteinaceous substances adsorbed to Au was examined for the following Au complexes: bovine albumin/Au, rat albumin/Au, IgG/Au, orosomucoid/Au, ovalbumin/Au, fetuin/Au, transferrin/Au, insulin/Au, low density lipoprotein/Au, alpha 2 macroglobulin/Au, and Au stabilized by polyethylene glycol. All these Au complexes bound to BCP although there were differences in the degree of affinity as judged by the number of BCP labeled and by the number of Au/complex particles present in the labeled BCP. Au stabilized by polyethylene glycol did not bind to BCP. Under the condition of these experiments, bovine albumin/Au had the highest degree of affinity for BCP and was therefore selected for the kinetic studies. PMID- 2885445 TI - Ultrastructural changes associated with the inhibition of monocyte chemotaxis caused by products of axenically grown Entamoeba histolytica. AB - The supernatant fluid of axenically grown Entamoeba histolytica-HM1 significantly modifies the ultrastructural features associated with monocyte chemotaxis as assayed in Boyden chambers. This morphological evidence supports the existence of a factor, monocyte locomotion inhibitory factor (MLIF), produced by E. histolytica that inhibits the in vitro locomotion of human monocytes. None of the leucocyte-locomotion modifying drugs included in this study (i.e., cytochalasin B, colchicine, vinblastine, and hydrocortisone) caused changes totally comparable with those induced by MLIF. The most striking feature was the increase of centriole-associated microtubules induced by MLIF and by cytochalasin-B. MLIF may inhibit monocyte locomotion by directly inducing excessive microtubule assembly, although a direct, if somewhat weak effect upon microfilaments cannot be excluded. The increase in microtubules could then represent a perhaps futile attempt of the microtubule organizing center to overcome the locomotion blockade that has occurred elsewhere in the cell. If active in vivo, MLIF may contribute to the paucity of inflammation in the advanced stages of invasive amebiasis, and consequently to the lack of scar tissue formation upon recovery from such lesions, as monocytes constitute an essential link to the healing process. PMID- 2885446 TI - Inosine monophosphate dehydrogenase activity in acute leukaemia. AB - Inosine monophosphate dehydrogenase (IMPD) is an important enzyme in de-novo purine synthesis. The level of IMPD activity has been suggested to determine whether acute leukaemia cells proliferate (if the activity is high) or differentiate (if IMPD activity is low). IMPD activity measured by the conversion of inosine monophosphate to xanthine monophosphate ranged from 12.5 to 87.0 (mean 49.4) pmol/h/10(6) cells in normal bone marrow. The levels were significantly raised in AML (range 14-374, mean 184 pmol/h/10(6) cells) and ALL (range 65-228, mean 172 pmol/h/10(6) cells). Normal tonsillar (B) lymphocytes showed higher levels (range 78-159, mean 110 pmol/h/10(6) cells) than resting peripheral blood T lymphocytes (range 8.8-51.2, mean 28.1 pmol/h/10(6) cells). In CLL, the results (range 19-173, mean 64.3 pmol/h/10(6) cells) were comparable to those of normal tonsillar B lymphocytes. IMPD levels could be related to cell cycle in PHA stimulated lymphocytes, since IMPD activity increased in parallel with increase in DNA synthesis measured by labelled thymidine incorporation. On the other hand, IMPD activity did not correlate with the proportion of proliferating cells measured on a FACS sorter in either AML or ALL or in normal tonsillar B cells. We conclude that IMPD levels are higher in B than T lymphocytes and in acute leukaemia blasts compared to more differentiated mixed bone marrow cells. The results do not suggest, however, that IMPD assay will be of value in differentiation of the various subtypes of acute leukaemia or of malignant haemopoietic cells from the equivalent normal cell at the same level of differentiation. PMID- 2885447 TI - [Study on the tolerance to antihypertensive medication III. Therapeutic regimens used in the study on the tolerance to antihypertensive medication. Cooperative Group for the Study on the Tolerance to Antihypertensive Medication]. PMID- 2885449 TI - Are nootropics a separate class of drugs? A differentiation in various models. AB - Psychostimulants, analeptics, and nootropics are three classes of drugs that have been used with varying success in the treatment of impaired brain functions. They all produce an excitatory and disinhibitory effect on the CNS but can be distinguished through their characteristic properties. Psychostimulants are drugs that lead to a general, but nonphysiological activation, which is followed by a phase of inhibition. Analeptics are drugs that stimulate the CNS, in particular the respiratory and circulatory centers, and which in high doses lead to convulsions. Nootropics are drugs that (in impaired brain functions) lead to a physiological activation of adaptation. PMID- 2885448 TI - [Efficiency and safety of ipecac syrup in the treatment of acute poisoning]. PMID- 2885450 TI - Placebo-controlled, double-blind study of haemodilution in peripheral arterial disease. AB - Twenty-four men who had stable claudication with long, collateralized femoropopliteal obstructions were treated by isovolaemic haemodilution and sham dilutions in a double-blind, placebo-controlled, crossover study. 3 weeks of haemodilution lowered haematocrit and blood viscosity and increased resting blood flow and pain-free walking distance. Sham treatment produced no such favourable changes. It is concluded that haemodilution therapy can be clinically effective in patients with arterial obstructions in the legs. It seems particularly promising when the vascular obstructions are such that low average shear stresses act on the blood in multiple, long collaterals. PMID- 2885451 TI - Role of genetic variation at the fibrinogen locus in determination of plasma fibrinogen concentrations. AB - Three restriction fragment length polymorphisms (RFLPs) of the fibrinogen genes were used in 91 individuals to investigate the role of genetic variation at this locus in the determination of plasma fibrinogen. The strongest association was with a polymorphism detected with the beta-fibrinogen probe and the enzyme BclI. The probe detects two alleles, designated B1 and B2. The individuals with the genotype B1B1 had a mean fibrinogen of 2.74 g/l; those with B2B2 had a mean fibrinogen of 3.69 g/l (a level previously associated with a strongly increased risk of ischaemic heart disease); and those heterozygous for the two alleles, with the genotype B1B2, had a mean of 2.98 g/l. Genetic variation at the fibrinogen gene locus accounted for 15% of the total phenotypic variance in fibrinogen. PMID- 2885452 TI - Fibroblasts from relatives of patients with hereditary breast cancer show fetal like behaviour in vitro. AB - Fetal and normal adult skin fibroblasts show distinctive migratory behaviour when plated on three-dimensional collagen gels. Skin fibroblasts from 13 of 15 patients with hereditary breast cancer showed fetal-like behaviour compared with only 1 of 12 age-matched healthy controls (p less than 0.015; Wilcoxon signed rank matched-pairs test). In addition, 10 of 15 first-degree relatives of patients with hereditary breast cancer showed a fetal-like fibroblast phenotype, compared with none of 7 surgical controls (p less than 0.009; chi 2 test). These results suggest that abnormalities expressed by skin fibroblasts may help identify people at increased risk of breast cancer developing. PMID- 2885453 TI - Community-acquired bacteraemia in African children. AB - To examine the frequency of community acquired bacteraemia in children in Kigali, Rwanda, blood cultures were obtained from 900 consecutive febrile children (T degrees greater than or equal to 39 degrees C) seen at an outpatient clinic over the course of a year. A pathogen was isolated from 112 children (12.4%): Salmonella typhi from 47, S enteritidis from 23, S typhimurium from 13, Streptococcus pneumoniae from 14, Staphylococcus aureus from 9, and Haemophilus influenzae from 3. Salmonella species represented 74% of the isolates. The children with S typhi bacteraemia were older (mean age 75 months) than those with bacteraemia due to other organisms. Controls consisted of febrile, nonbacteraemic children without (group I) or with (group II) Plasmodium falciparum parasitaemia. Bacteraemic children were older and presented more frequently with diarrhoea, vomiting, and dehydration, but less frequently with convulsions than controls. The rate of hospital admission was higher among bacteraemic children (61%) than among group I (39%) or group II (46%) controls. The case-fatality rate was similar in the three groups (9.3% versus 2.9% and 7.3%). Community-acquired bacteraemia in Rwandese children is common and is mainly caused by Salmonella species. PMID- 2885455 TI - Generalised osteoarthritis: an evolutionary problem? AB - Polyarticular osteoarthritis (OA) has a distinctive pattern of joint involvement. Some joints, such as the first metatarsophalangeal joint, are commonly affected, whereas others, such as the shoulder, are rarely involved. This distinct pattern of involvement may represent a subset of OA--generalised OA. Analysis of the pattern of change in joint function in the recent evolutionary development of man suggests a hypothesis that explains the pattern of joint involvement in generalised OA. Joints most commonly affected have undergone recent rapid evolutionary change to a new function that has resulted in increased loading. These joints are therefore relatively underdesigned, have little functional reserve, and are likely to fail often and early. Joints that are rarely affected have changed to a function with reduced loading. They are relatively overdesigned and have a large functional reserve, so fail rarely and late. PMID- 2885454 TI - Prevention of emesis in patients receiving cytotoxic drugs by GR38032F, a selective 5-HT3 receptor antagonist. AB - 15 patients receiving cytotoxic drugs (other than cisplatin) that had previously produced nausea and vomiting refractory to first-line antiemetics were given a selective 5-HT3 receptor antagonist (GR38032F), 4 mg intravenously and 4 mg orally, immediately before chemotherapy, the oral dose being repeated 5 and 10 h later. Nausea, vomiting, and side-effects were recorded for the ensuing 24 h. The 15 patients received a total of thirty-one courses of chemotherapy. Only 1 patient vomited. The only adverse events were dryness of the mouth in 1 patient, mild sedation in 1, and diarrhoea in 1, and these were not clearly drug related. PMID- 2885456 TI - Depression, stress, and immunity. PMID- 2885457 TI - New awakening in anaesthesia--at a price. PMID- 2885459 TI - Testing taste. PMID- 2885458 TI - 5-HT3 receptor antagonists: a new class of antiemetics. PMID- 2885460 TI - Slap on the wrist for another missed diagnosis. PMID- 2885461 TI - Reduction of premature mortality by high physical activity: a 20-year follow-up of middle-aged Finnish men. AB - The association of physical activity level with the risk of death was analysed for a cohort of 636 healthy Finnish men aged 45-64 years followed up for 20 years. 39% of the cohort were classed as highly active physically at baseline in 1964. Up to 1984 there were 287 deaths, 106 of them due to coronary heart disease (CHD). During the first-two thirds of the follow-up, men with high physical activity had a lower risk of death than did men with low physical activity. During the last third, the survival curves of the men with high and low physical activity gradually converged. Of the men who died, those with high physical activity lived 2.1 years longer (p = 0.002) than those with low physical activity, after adjustment for age, smoking, blood pressure, serum cholesterol, and body mass index. This difference was due mainly to fewer CHD deaths among the highly active group. Low physical activity was clearly weaker than smoking as a predictor of risk of death. High physical activity may thus independently prevent premature death among middle-aged men, but it probably does not prolong the maximum achievable life-span. PMID- 2885462 TI - Corticosteroids as adjunctive therapy in treatment of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. AB - 10 patients with the acquired immunodeficiency syndrome whose respiratory failure due to Pneumocystis carinii pneumonia (PCP) was deteriorating rapidly had 7 days of intravenous methylprednisolone added to their antibiotic regimen. 8 similar patients were treated with antibiotic therapy alone. 9 of the 10 methylprednisolone-treated patients survived their episode of PCP, compared with 2 of the 8 conventionally treated patients. Clinical improvement was evident within 2 days of the start of steroid therapy, and in none of the 10 patients did clinical deterioration or recurrence of PCP occur on cessation of steroid therapy. In 1 steroid-treated patient disseminated herpes zoster developed 2 days after discontinuation of methylprednisolone. Methylprednisolone seems to be a useful adjunctive therapeutic agent for patients with AIDS in whom Pneumocystis carinii is the sole respiratory pathogen. PMID- 2885463 TI - Exchanging kidney transplants--is it worth it? PMID- 2885464 TI - A new kidney, a new life. PMID- 2885465 TI - Acupuncture and scepticism. PMID- 2885466 TI - Coronary heart disease mortality rates. PMID- 2885467 TI - Pursed-lip breathing reduces hyperventilation-induced bronchoconstriction. PMID- 2885468 TI - Environmental source of manganese on Groote Eylandt, northern Australia. PMID- 2885469 TI - Programming of bone marrow donor for a leukaemic sibling. PMID- 2885470 TI - Local treatment of ulcers in diabetic foot with human growth hormone. PMID- 2885471 TI - Toxicity of topical sugar. PMID- 2885472 TI - Cyclosporin in pulmonary sarcoidosis. PMID- 2885474 TI - Doxycycline prophylaxis in malaria. PMID- 2885473 TI - Free muscle flap for treatment of iatrogenic pneumocephalus. PMID- 2885475 TI - Anti-neutrophil-cytoplasm antibodies in Wegener's granulomatosis are not directed against alkaline phosphatase. PMID- 2885476 TI - Shulman syndrome, a scleroderma subtype caused by Borrelia burgdorferi? PMID- 2885478 TI - Choroid plexus cysts in the fetus. PMID- 2885477 TI - Pleural effects of tremolite in north-west Greece. PMID- 2885480 TI - Professional review in the USA. PMID- 2885479 TI - Meta-analysis. PMID- 2885482 TI - Hearing problems in elderly people. PMID- 2885481 TI - Unfavourable results and drug company trials. PMID- 2885483 TI - Trials in acute stroke. PMID- 2885484 TI - Bed-nets and protection against malaria. PMID- 2885485 TI - Adverse reaction to 5-HT3 antagonist ICS 205930. PMID- 2885486 TI - Myelotoxicity of methotrexate, mitozantrone, and mitomycin C. PMID- 2885487 TI - Lead and IQ. PMID- 2885488 TI - Haemorrhagic colitis and verotoxin-producing Escherichia coli O157 in Belgium. PMID- 2885489 TI - Malnutrition-related diabetes. PMID- 2885490 TI - Bupivacaine concentration and mode of delivery. PMID- 2885491 TI - Systemic absorption from prednisolone rectal foam in ulcerative colitis. PMID- 2885492 TI - Unilateral analgesia following injection of fentanyl into the lumbosacral plexus. PMID- 2885494 TI - HIV transmission from monkey to man. PMID- 2885493 TI - LHRH analogues and bone loss. PMID- 2885495 TI - True HIV-1 infection in a pygmy. PMID- 2885496 TI - Wernicke's encephalopathy in AIDS. PMID- 2885497 TI - Aetiology of oesophageal cancer. PMID- 2885498 TI - Postpartum collapse due to acute dilated cardiomyopathy. PMID- 2885499 TI - Echocardiographic evidence of altered cardiac diastolic function in ankylosing spondylitis. PMID- 2885500 TI - Recurrence of loin pain/haematuria syndrome after renal autotransplantation. PMID- 2885502 TI - The Na+-H+ antiport in essential hypertension. PMID- 2885501 TI - Eicosapentaenoic and dihomo-gamma-linolenic acids. PMID- 2885503 TI - Serological diagnosis of primary Sjogren's syndrome by means of human recombinant La (SS-B) as nuclear antigen. AB - Human recombinant La nucleoprotein was purified from cultures of Escherichia coli containing a vector with a 1.4 kilobase cDNA encoding La; the nucleoprotein was used to test for antinuclear antibodies (ANA) to La. Serum samples from 260 patients with autoimmune diseases associated with ANA and 100 healthy subjects were tested by an enzyme-linked immunosorbent assay (ELISA). Samples from 47 (94%) of 50 patients with primary Sjogren's syndrome and 1 (7%) of 14 patients with secondary Sjogren's syndrome reacted with the recombinant La. No reactivity was demonstrated in 196 patients with other ANA-associated autoimmune diseases or in 100 healthy subjects. The study confirms the high correlation between ANA, anti-La, and primary Sjogren's syndrome and shows how gene cloning can provide large quantities of human autoantigens for use in highly specific and sensitive diagnostic assays. PMID- 2885504 TI - Effect of cigarette smoking on the pattern of arterial blood flow: possible insight into mechanisms underlying the development of arteriosclerosis. AB - By means of non-invasive multichannel doppler ultrasound measurements, cigarette smoking in healthy subjects was shown to increase arterial wall stiffness and to alter the pattern of arterial blood flow, decreasing the pulsatility index. The pattern of blood flow seems to be a contributory factor in the development of arteriosclerosis, and these findings may provide insight into the underlying mechanisms. PMID- 2885505 TI - Safety and efficacy of high-dose sodium stibogluconate therapy of American cutaneous leishmaniasis. AB - 40 patients with American cutaneous leishmaniasis caused primarily by Leishmania braziliensis panamensis were treated with sodium stibogluconate in a double blind, randomised controlled trial. Nine weeks after starting treatment, all 19 patients treated with 20 mg Sb/kg per day for twenty days were cured but 5 of 21 patients treated with 10 mg Sb/kg per day for twenty days had persistent active disease (p less than 0.05). Both treatment regimens were well tolerated and they were associated with a similar incidence of reversible toxic effects. Existing recommendations for therapy of American cutaneous leishmaniasis with sodium stibogluconate are inadequate for some patients, and higher doses are both safe and efficacious. PMID- 2885506 TI - Cardiorespiratory arrest and autonomic neuropathy in AIDS. AB - Four of five patients with AIDS and pulmonary infection had syncopal reactions as a result of fine-needle aspiration of the lung; in one patient the reaction was fatal. Subsequently, in one of these patients and four further patients with AIDS or human immunodeficiency virus (HIV) infection, the autonomic nervous system proved to be abnormal. This preliminary evidence suggests HIV infection may be associated with an autonomic neuropathy, which may expose these patients to particular risk after invasive procedures. PMID- 2885507 TI - Provision of renal replacement therapy for diabetic patients in the UK. PMID- 2885509 TI - Amiodarone and the thyroid: the Janus response. PMID- 2885508 TI - Antibiotics for exacerbations of chronic bronchitis? PMID- 2885510 TI - Electrodiagnosis of ulnar neuropathies. PMID- 2885511 TI - EDRF reveals its identity. PMID- 2885512 TI - Meta-analysis of randomised controlled trials of nicotine chewing-gum. AB - A meta-analysis was made of fourteen randomised controlled trials that evaluated the efficacy of nicotine chewing-gum in stopping patients smoking. The combined success rates in specialised cessation clinics are significantly higher with nicotine gum (27%) than with placebo gum (18%) at 6 months (n = 734), and 23% and 13% at 12 months, respectively. In contrast, success rates in general medical practices are similar with nicotine gum (11.4%) and with placebo gum (11.7%) at 6 months (n = 1022). However, in general practices, the success rates are 17% for nicotine gum and 13% for the no gum control at 4-6 months, and 9% and 5% at 12 months, a significant difference between the treatments at each time (n = 2238). The data suggest that proper use of nicotine gum in specialised clinics will increase the rate of stopping patients smoking. The use of the gum in general medical practices is questionable. PMID- 2885515 TI - Choice and ordering of medical school applications: cause for concern. AB - The probability of admission to medical school in the UK can be predicted from the choices of schools and their order on the UCCA form, even after academic factors have been taken into account. The effect may of itself influence a candidate's chance of admission by a factor of about four times. This situation justifies the recurrent complaints of applicants about the problems of medical school choice and ordering. The disadvantage imposed on many applicants would be reduced if rank ordering of choices was replaced by alphabetical ordering. PMID- 2885513 TI - Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. AB - Measurements of haemostatic function and metabolic and angiographic indices of risk were included in a prospective cohort study of variables predictive of recurrences within 3 years in 109 unselected men with a first myocardial infarction (MI) before the age of 45. In the course of follow-up, 16 patients had at least one reinfarction (fatal recurrences in 9 and nonfatal in 7) and 1 died suddenly. High plasma concentrations of the fast-acting plasminogen activator inhibitor were independently related to reinfarction along with dyslipoproteinaemia involving VLDL and HDL, poor left ventricular performance, and multiple-vessel coronary artery disease. Besides being independently associated with reinfarction in the present population, high triglyceride levels were possibly connected with a predisposition to thrombosis through a coexisting high level of plasminogen activator inhibitor. The data indicate that reduced fibrinolytic capacity due to increased plasma levels of the plasminogen activator inhibitor predisposes to reinfarction in a complex interplay with atherogenic factors, multiple coronary lesions, and compromised left ventricular function. PMID- 2885514 TI - Evidence on inequality in health from a national survey. AB - The debate about social inequality in health in Britain has so far been based principally on mortality rates. A survey of morbidity and fitness in a large representative sample of adults living in private households in England, Wales, and Scotland reveals striking differences between social classes in self-defined health status, the reported incidence of illness, the prevalence of chronic disease, and measured physiological fitness. The disadvantage in health status does not simply relate to a minority in the poorest social circumstances but appears to be related in a very regular way to the social class structure. PMID- 2885516 TI - Persistent fatigue and depression in patient with antibody to human B lymphotropic virus. PMID- 2885517 TI - Testing blood donors for non-A, non-B hepatitis: irrational, perhaps, but inescapable. PMID- 2885518 TI - In vivo 31P NMR spectroscopy for evaluation of osteoporosis. PMID- 2885519 TI - Prognosis of meningococcal septicaemia. PMID- 2885520 TI - Telethermography in infant's emotional behavioural research. PMID- 2885521 TI - Immediate anticonvulsive drug monitoring in management of epilepsy. PMID- 2885522 TI - Group-specific component and HIV infection. PMID- 2885523 TI - Female-to-female transmission of HIV. PMID- 2885524 TI - Safety of albumin preparations manufactured from plasma not tested for HIV antibody. PMID- 2885525 TI - Histiocytosis syndromes in children. PMID- 2885526 TI - Human papillomavirus type 16 DNA in anal squamous cell carcinoma. PMID- 2885527 TI - The bran wagon. PMID- 2885528 TI - Poliovaccination in the Gambia. PMID- 2885530 TI - Risk of unexplained stillbirth at different gestational ages. PMID- 2885529 TI - Yoghurt with Bifidobacterium longum reduces erythromycin-induced gastrointestinal effects. PMID- 2885531 TI - Appearance of chloroquine-resistant falciparum malaria in Swaziland. PMID- 2885532 TI - Antibiotic policy and infective exacerbation of obstructive airways disease. PMID- 2885533 TI - Bacterial pharyngitis. PMID- 2885534 TI - Doctors, patients, and possession of illegal drugs. PMID- 2885535 TI - Prescribing for drug addicts. PMID- 2885536 TI - Quality-adjusted life-years. PMID- 2885538 TI - Organ sharing in transplantation. PMID- 2885537 TI - Golf syncope. PMID- 2885539 TI - Abortion and mental handicap. PMID- 2885541 TI - Health workers and peace. PMID- 2885540 TI - Food irradiation and bacterial toxins. PMID- 2885542 TI - Central-nervous-system lesions detected by magnetic resonance imaging in an HTLV 1 antibody positive symptomless individual. PMID- 2885543 TI - HTLV-I, brain abnormalities on magnetic resonance imaging, and relation with multiple sclerosis. PMID- 2885544 TI - Child abuse and the doctor's duty of care. PMID- 2885545 TI - The evils of delay. PMID- 2885546 TI - Persistent measles virus genome in autoimmune chronic active hepatitis. AB - A radiolabelled 50-base oligonucleotide complementary with the measles virus gene encoding the nucleocapsid was used as a probe to identify persistent measles virus genome in the lymphocytes from patients with autoimmune chronic active hepatitis (AICAH). Positive hybrids were found in 12 of 18 patients, and correlated strongly with high antibody titres to measles. Among the 45 controls, positive hybrids were found in 1 patient with measles, 1 of 3 patients with systemic lupus erythematosus, and 2 of 4 patients with cryptogenic cirrhosis. Persistence of part of the measles virus genome in AICAH may have important implications in the pathogenesis of the liver disease, and possibly in other disorders such as systemic lupus erythematosus, multiple sclerosis, and Paget's disease where an abnormal immune response to measles has been observed. PMID- 2885548 TI - Needle exchange and HIV infection. PMID- 2885549 TI - HIV and schizophrenia. PMID- 2885547 TI - HIV-related deaths in HIV antibody-positive haemophilic patients. PMID- 2885550 TI - Safety of splenoportovenography as an outpatient procedure. PMID- 2885551 TI - Usefulness of immunomodulating agents. PMID- 2885553 TI - Private homes for elderly patients. PMID- 2885552 TI - Brain death. PMID- 2885554 TI - Copycat suicide attempts. PMID- 2885555 TI - Relaxing the 10-day rule. PMID- 2885556 TI - Hepatotoxicity with actinomycin D. PMID- 2885557 TI - Transient impairment of renal function and myoglobin turnover after generalised seizures. PMID- 2885558 TI - Cytomegalovirus infection and aplastic crisis in glucose-6-phosphate dehydrogenase deficiency. PMID- 2885559 TI - Effect of aluminium on in-vitro tetrahydrobiopterin synthesis in brain preparations. PMID- 2885560 TI - Cytomegalovirus immune bone-marrow donors and interstitial pneumonitis. PMID- 2885561 TI - Decreased stability of prostacyclin after acute myocardial infarction. PMID- 2885562 TI - Flumazenil: a possible treatment for benzodiazepine withdrawal anxiety. PMID- 2885564 TI - Absence of secretory response in jejunal biopsy samples from children with cystic fibrosis. PMID- 2885563 TI - Cystic fibrosis and bacterial conversion of oleic acid to a cathartic, 10 hydroxystearic acid. PMID- 2885565 TI - Beta-blockers and lipophilicity. PMID- 2885567 TI - How many oocytes/embryos should be transferred? PMID- 2885566 TI - Atopy and childhood coeliac disease. PMID- 2885568 TI - Pivampicillin for endocarditis. PMID- 2885569 TI - Erythrocyte vacuolation in haemolytic anaemia during shigellosis. PMID- 2885570 TI - Left atrial dimension during early puerperium. PMID- 2885571 TI - Brasilian purpuric fever in central Australia. PMID- 2885572 TI - Intermediate-density lipoproteins and progression of coronary artery disease in hypercholesterolaemic men. AB - Lipoprotein mass concentrations were measured by analytical ultracentrifugation in a subset of 57 hypercholesterolaemic male participants in the National Heart, Lung, and Blood Institute Type II Coronary Intervention Study. 2-year changes in levels of intermediate-density lipoproteins (IDL) of flotation rate 12-20 were strongly predictive of progression of coronary artery disease at 5 years. Changes in serum mass concentrations of low-density lipoproteins (LDL; flotation rate 0 12), very-low-density lipoproteins (VLDL; flotation rate 20-400), high-density lipoproteins (HDL), and the HDL2 and HDL3 subfractions did not differ significantly between men with and without definite progression of coronary artery disease. The relation of IDL mass to disease progression remained significant (p less than 0.05) after adjustment for group assignment to cholestyramine treatment or placebo and was only slightly reduced (p less than or equal to 0.06) by adjustment for changes in LDL mass concentrations. Changes in IDL mass and ratios of HDL-cholesterol to total-cholesterol or LDL-cholesterol were inversely correlated and had a similar ability to predict progression. The findings are consistent with earlier evidence that IDL are directly involved in the development of coronary artery disease and suggest that ratios of HDL cholesterol to total-cholesterol or LDL-cholesterol may be indicators of coronary disease risk partly owing to relations with IDL metabolism. PMID- 2885573 TI - Loss of HBsAg with interferon therapy in chronic hepatitis B virus infection. AB - 46 male chronic hepatitis B virus (HBV) carriers with active viral replication were randomised, with stratification for histology and sexual preference, to receive six months' lymphoblastoid interferon or no therapy. After nine to eighteen months' follow-up, HBeAg was no longer detectable and anti-HBe was present in 6 of the 23 treated patients. HBsAg was not detectable in 5 of these patients and 3 had anti-HBs. All of the controls remained positive for HBeAg and HBsAg. Seroconversion from HBeAg to anti-HBe was preceded in all cases by a pronounced increase in serum aspartate aminotransferase levels of more than ten times the upper limit of normal at eight to twelve weeks; this response was exclusively associated with interferon therapy. These results suggest that loss of HBsAg and a hepatitis-like illness in the third month of therapy are direct effects of interferon treatment. PMID- 2885574 TI - Overexpression of the c-erbB-2 oncoprotein in human breast carcinomas: immunohistological assessment correlates with gene amplification. AB - Amplification of the human protooncogene c-erbB-2 was found in 12 of 36 human breast tumours and was associated with increased levels of expression of the c erbB-2 protein, measured both by immunohistological staining and by western blotting. The use of immunohistological staining to detect the level of expression of the c-erbB-2 protein in human breast adenocarcinomas may be of value in predicting tumour behaviour. PMID- 2885576 TI - Postoperative cardiac death. PMID- 2885577 TI - Immunisation policy: recipes for success. PMID- 2885575 TI - Sensitive assays for viral antibodies in saliva: an alternative to tests on serum. AB - Paired serum and saliva specimens were tested by conventional assays and by IgG capture radioimmunoassays (GACRIA) and enzyme-linked immunosorbent assays (GACELISA) for antibody to hepatitis A virus (HAV, 100 pairs), human immunodeficiency virus (HIV, 53), hepatitis B virus core (HBc, 62), and rubella virus (30). Conventional assays failed to detect viral antibodies in the saliva of 93 of 119 seropositive subjects. However, GACRIA detected the antibodies in both serum and saliva of all subjects seropositive by conventional tests, except 2 saliva specimens false-negative for anti-HBc and 1 false-negative for anti rubella-virus. For anti-HIV and anti-HBc serum and saliva GACRIA reactivities did not differ significantly, but anti-HAV and anti-rubella-virus GACRIA reactivities were stronger in serum than saliva. GACRIA and GACELISA results on saliva for the four antibodies correlated closely; for anti-HAV and anti-HIV GACELISA and GACRIA were equally accurate. For both saliva and serum, GACRIA was superior to an IgA capture assay in detecting anti-HAV and anti-HIV. PMID- 2885578 TI - Diet and peptic ulcer. PMID- 2885580 TI - Colostomy or ileostomy? PMID- 2885579 TI - Lactitol. PMID- 2885583 TI - New scourge: old challenge. PMID- 2885582 TI - Maternal rubella at St Thomas' Hospital in 1978 and 1986: support for augmenting the rubella vaccination programme. AB - The effects of the rubella epidemics in 1978 and 1986 among patients attending antenatal clinics at St Thomas' Hospital were compared. Although many pregnant women who had been exposed to rubella-like illnesses were investigated in both 1978 (269) and 1986 (160), the number of cases of maternal rubella was substantially lower in 1986 (1) than in 1978 (17). Rubella vaccination of 11-14 year-old girls was introduced in the United Kingdom in 1970, but 10% of our patients were susceptible and only 36% gave a definite history of vaccination. Despite the smaller number of maternal rubella cases, substantial resources were expended on assessing patients who had been exposed to or who presented with rubella-like illnesses. In 1978 an intensification of the selective rubella vaccination campaign was recommended, but experience in the 1986 epidemic supports the view that the programme should be augmented by vaccination of preschool children with a combined measles, mumps, and rubella vaccine, with a view to rubella eradication. PMID- 2885581 TI - Risk of therapy-related leukaemia and preleukaemia after Hodgkin's disease. Relation to age, cumulative dose of alkylating agents, and time from chemotherapy. AB - 391 patients treated intensively for Hodgkin's disease were followed for up to 15 years to evaluate the risk of therapy-related acute non-lymphocytic leukaemia (t ANLL) and preleukaemia. Only two independent factors, patient age and cumulative dose of alkylating agents, were related to the risk of t-ANLL. The hazard rate of t-ANLL was roughly proportional to the square of patient age and to the total cumulative dose of alkylating agents. In 320 patients treated with alkylating agents the cumulative risk of t-ANLL increased steadily from 1 year after the start of treatment and reached 13.0% (SE 3.0) at 10 years after which time there were no further cases. Calculated from cessation of therapy with alkylating agents, however, the cumulative risk curve increased steeply during the first 1-2 years then gradually levelled out and no new cases were observed beyond 7 years. With a 15-year follow-up the general risk of solid tumours was not increased. PMID- 2885584 TI - Rapid diagnosis of herpes simplex virus type 1 encephalitis by radioactive genome detection in cerebrospinal fluid. PMID- 2885585 TI - Strongyloides stercoralis as candidate co-factor for HTLV-I-induced leukaemogenesis. PMID- 2885586 TI - Penicillamine may detoxify copper in Wilson's disease. PMID- 2885587 TI - Spiral organisms in the gastric antrum. PMID- 2885588 TI - Bolus streptokinase after myocardial infarction. PMID- 2885589 TI - Opsonophagocytic activity of intravenous immunoglobulins. PMID- 2885590 TI - Resistant hypertension and high-pressure chronic retention. PMID- 2885591 TI - Sex ratio in outbreaks of parvovirus B19 infection. PMID- 2885592 TI - Unusual reaction to morphine. PMID- 2885593 TI - Describing the AIDS epidemic. PMID- 2885594 TI - Methods for projecting the AIDS epidemic. PMID- 2885595 TI - AIDS definition for Africa. PMID- 2885596 TI - Diagnosis of tuberculous meningitis by detection of tuberculostearic acid in cerebrospinal fluid. AB - Tuberculostearic acid, a structural component of Mycobacterium tuberculosis, was identified by gas chromatography/mass spectrometry with selected ion monitoring in cerebrospinal fluid (CSF) from 13 patients with proven and 8 out of 9 patients with suspected tuberculous meningitis; the negative result was in a patient whose symptoms and CSF abnormalities may have been due to systemic lupus erythematosus. Tuberculostearic acid was found in the CSF of only 1 patient out of 87 with non tuberculous meningitis or non-infectious disorders; the single false-positive result was probably caused by intrathecal treatment with amikacin. Other aminoglycosides and antituberculous drugs did not interfere with the assay. In serial CSF samples from patients with tuberculous meningitis tuberculostearic acid was still present after 8 months of continuous supervised chemotherapy. Detection of tuberculostearic acid in CSF is a rapid, sensitive, and specific test for tuberculous meningitis, and can be used for retrospective diagnosis in patients who have been started on therapy. PMID- 2885597 TI - Prospective study of cellular immunity to hepatitis-B-virus antigens from the early incubation phase of acute hepatitis B. AB - Cellular immunity to hepatitis-B-virus (HBV) antigens was followed prospectively in five patients who were identified in the early incubation phase of acute HBV infection, between 30 and 70 days before the onset of liver damage. Cellular immunity to pre-S antigens was the first detectable immune response, appearing 30 days before the first rise in serum aminotransferases in every case. T-cell sensitisation to HBcAg followed, with IgM anti-HBc appearing 10 days later. A cellular immune response to HBsAg was the last to appear, 10 days before the onset of liver damage. These cellular immune responses are the earliest host responses to the virus infection and could be critical in initiating and directing the processes of liver damage and viral clearance. PMID- 2885598 TI - Circulating cytotoxic protein generated after ethanol consumption: identification and mechanism of reaction with cells. AB - Serum obtained from healthy volunteers 6-7 h after consumption of 60-95 g of ethanol contained cytotoxic activity against mouse A9 cells and all of six human cell lines tested. Affinity chromatography of such sera demonstrated that at least some of the cytotoxic molecules consisted of altered albumin. Complexes formed by the reaction of 14C-acetaldehyde with 125I-labelled human serum albumin in vitro were also cytotoxic. After treatment with a reducing agent, sodium borohydride, the cytotoxicity of both post-alcohol serum and the acetaldehyde albumin complexes fell sharply, suggesting that the cytotoxic activity resided in the unstable Schiff bases formed during the first stage of reaction between the acetaldehyde and proteins. A detailed analysis of the reaction between the double labelled acetaldehyde-albumin complexes and K562 cells revealed that the cytotoxic activity resulted from the release of acetaldehyde from such complexes and the preferential binding of the free acetaldehyde to the target cells. PMID- 2885599 TI - Prednisolone does not prevent post-herpetic neuralgia. AB - In a randomised, double-blind, controlled study of the effect of prednisolone on the development of post-herpetic neuralgia 78 patients with herpes zoster whose pain and exanthema had been present for less than 96 h were given 800 mg acyclovir five times daily for 7 days and prednisolone in a total dose of 575 mg, starting with 40 mg daily in the first week and tapering off over the next 2 weeks. 18 (23%) of the patients had post-herpetic neuralgia at 6 months after the acute zoster, 9 (24.3%) having received prednisolone and 9 (22.5%) placebo. The 95% CI for the difference between the placebo and prednisolone groups in the proportion of patients having pain at 6 months was minus 17% to plus 20%. Prednisolone, however, relieved pain for the first 3 days. The 1-2 week interval between admission and reappearance of pain and development of triggered pain seems to be the time needed to establish neuralgia. Once established, the type and intensity of pain remained largely unaltered. PMID- 2885600 TI - Fetal breathing movements as predictor of favourable pregnancy outcome after oligohydramnios due to membrane rupture in second trimester. AB - In 11 pregnancies complicated by oligohydramnios due to spontaneous rupture of the membranes in the second trimester of pregnancy fetal breathing movements were assessed regularly by ultrasonographic examinations. In the 6 cases in which fetal breathing movements were detected the babies were liveborn and there was no evidence of pulmonary hypoplasia or the other non-renal features of Potter's syndrome. In the other 5 cases there were no fetal breathing movements. 1 pregnancy was terminated electively, and 1 ended in an intrauterine death; the remaining 3 infants died in the neonatal period. All 5 cases showed necropsy evidence of pulmonary hypoplasia. These findings indicate that premature and prolonged rupture of membranes in the second trimester of pregnancy does not uniformly result in a poor prognosis. They suggest that fetal breathing movements could be used as a predictor of favourable neonatal outcome. PMID- 2885601 TI - EDRF. PMID- 2885602 TI - Thrombolytic therapy for acute myocardial infarction. PMID- 2885603 TI - Home monitoring for infantile apnoea. PMID- 2885604 TI - Who consults the GP? PMID- 2885605 TI - Euthyroid hyperthyroxinaemia. PMID- 2885606 TI - Macrophages and atherogenesis. PMID- 2885608 TI - Human papillomavirus type 5 and skin cancer in renal allograft recipients. PMID- 2885607 TI - Methotrexate/nitrous-oxide toxic interaction in perioperative chemotherapy for early breast cancer. PMID- 2885609 TI - Isoniazid-induced valproic-acid toxicity, or vice versa. PMID- 2885610 TI - Desialylated transferrin as a marker of excessive alcohol intake. PMID- 2885611 TI - Lead and children's IQ. PMID- 2885612 TI - Campylobacter pylori infection in homosexuals. PMID- 2885613 TI - Shock-wave lithotripsy of gallstones with second-generation device without conventional water bath. PMID- 2885614 TI - Use of DNA markers linked to cystic fibrosis gene to resolve equivocal sweat test results. PMID- 2885615 TI - Indirect cystic fibrosis carrier detection. PMID- 2885616 TI - Autoimmunity, diabetes, and cystic fibrosis. PMID- 2885617 TI - Antigliadin and antireticulin antibodies in screening for coeliac disease. PMID- 2885618 TI - Antigliadin antibodies at onset of diabetes in children. PMID- 2885619 TI - Breaking the cycle of HTLV-I transmission via carrier mothers' milk. PMID- 2885620 TI - Risk of adult T-cell leukaemia/lymphoma in HTLV-I carriers. PMID- 2885621 TI - Boycotts and medicine. PMID- 2885622 TI - Smoke screen around oral snuff. PMID- 2885623 TI - Doses from Chernobyl radiocaesium. PMID- 2885624 TI - Quality of life. PMID- 2885625 TI - DNA diagnostic costs. PMID- 2885626 TI - Testis position and age at orchidopexy. PMID- 2885627 TI - Acetazolamide in treatment of epilepsy. PMID- 2885628 TI - Rapid correction of hypokalaemia via the oral route. PMID- 2885629 TI - Preserved hearing following excision of acoustic tumours. PMID- 2885630 TI - Positive formaldehyde-RAST after prolonged formaldehyde exposure by inhalation. PMID- 2885631 TI - Treatment of chronic Salmonella carriers with ciprofloxacin. PMID- 2885632 TI - Ultrasonography for early diagnosis of hereditary angioneurotic oedema. PMID- 2885633 TI - Double HIV-1 and HIV-2 seropositivity among blood donors. PMID- 2885634 TI - Immunology of human skin and susceptibility to HIV infection. PMID- 2885635 TI - Serological evidence for HIV infection in Cuban immigrants in 1980. PMID- 2885636 TI - AIDS and the witch doctor. PMID- 2885637 TI - Adjuvant tamoxifen in the management of operable breast cancer: the Scottish Trial. Report from the Breast Cancer Trials Committee, Scottish Cancer Trials Office (MRC), Edinburgh. AB - In a trial that began in 1978, 1312 evaluable patients under 80 years of age who either had negative axillary nodes or were postmenopausal with positive axillary nodes were randomised to receive adjuvant tamoxifen 20 mg daily for 5 years, or tamoxifen for the treatment of first relapse. Estimates of oestrogen receptor (ER) content of primary tumour specimens were made in 57%. There has been a highly significant delay in relapse in the adjuvant arm of the trial. This benefit supersedes that from tamoxifen given as treatment for recurrent disease in control-arm patients (93% received this) so that benefit from adjuvant tamoxifen was maintained in the overall survival comparisons. This improvement seems to be independent of nodal and menopausal status. It does not differ significantly with ER level, although the greatest benefit in disease-free survival is in patients with levels of 100 fmol/mg protein or more. PMID- 2885639 TI - Ultrafiltration with an isosmotic solution during long peritoneal dialysis exchanges. AB - The potential of a starch-derived glucose polymer (molecular weight 16,800) as an osmotic agent for peritoneal dialysis was evaluated. A dialysate isosmotic to uraemic serum (302 [SEM 1.3] mOsm/kg) containing 5% glucose polymer (9.4 mmol/l) was compared with hypertonic (332 [1.0] mOsm/kg) 1.36% glucose (76 mmol/l) solution for ultrafiltration, solute transport, and carbohydrate absorption over 6 h and 12 h peritoneal dialysis exchanges. Glucose polymer solution produced substantially greater net ultrafiltration than glucose, while maintaining stable dialysate osmolality throughout the exchanges. At 6 h and 12 h, 14.4% and 28.1% of glucose polymer had been absorbed, compared with 61.5% and 83.0% of glucose; thus, glucose polymer provided less than 50% of the calorie load of the glucose dialysate per unit volume of ultrafiltrate. There was a 7-9-fold increase in serum maltose with glucose polymer. This high-molecular-weight glucose polymer produced sustained ultrafiltration even when dialysate osmolality remained within the physiological range, by a mechanism resembling "colloid" osmosis. It is a safe and effective osmotic agent but its long-term effects need further study. PMID- 2885638 TI - Impact of T-cell depletion on outcome of allogeneic bone-marrow transplantation for standard-risk leukaemias. AB - 71 leukaemic patients having HLA-matched bone-marrow transplants (BMT) were randomised to receive whole marrow (group A) or marrow depleted of T cells by treatment with monoclonal antibodies (anti CD4-CD5-CD8, group B; anti CD2-CD5 CD7, group C) plus complement. All patients received cyclophosphamide and total body irradiation before transplantation and cyclosporin after BMT. Marrow treatment removed 97% of T cells (median) in group B and 99% in group C. Although both serious and mild graft-versus-host disease (GVHD) were reduced in T-cell depleted patients, graft failure and relapse were increased. Graft failure was caused by GVHD and transplant complications in the controls and by rejection and relapse in the T-cell depleted groups; relapse-free survival did not differ between the groups. Without better control of host immunity and of the residual leukaemia T-cell depletion of the marrow, BMT should not be pursued in standard risk patients. PMID- 2885640 TI - Transplantation of liver, heart, and lungs for primary biliary cirrhosis and primary pulmonary hypertension. AB - Liver, heart, and lung replacement was performed in a woman with severe pulmonary hypertension, cardiorespiratory failure, and end-stage primary biliary cirrhosis. The main surgical considerations were the staging of the various parts of the operation in relation to cardiopulmonary bypass and performing the recipient procedures as expeditiously as possible to reduce the bypass time to a minimum. The patient was able to leave hospital on the 46th postoperative day on low doses of immunosuppressive agents, with excellent liver and cardiopulmonary function. This early satisfactory outcome shows the feasibility and potential of the procedure: such combined allografting may be a suitable treatment in carefully selected cases of advanced liver and lung disease from other causes. PMID- 2885641 TI - Faecal bile acids, dysplasia, and carcinoma in ulcerative colitis. AB - A prospective study was undertaken between 1974 and 1985 of 102 patients with extensive ulcerative colitis (UC) of more than 10 years' duration. Faeces were collected for measurement of faecal bile acid concentrations (FBA), and the clinical outcome was recorded. The average faecal bile acid value among the 14 patients who showed carcinoma or definite dysplasia in the excised large bowel (9.86 [SE 0.81] mg/g FBA) was higher than in the 88 patients without dysplasia or carcinoma (7.51 [0.24] mg/g). These results lend support to the theory that bile acids are causally related to colorectal cancer. PMID- 2885643 TI - Adjuvant tamoxifen in early breast cancer. PMID- 2885642 TI - Vaccinia recombinant expressing Lassa-virus internal nucleocapsid protein protects guineapigs against Lassa fever. AB - The Lister strain of vaccinia virus was used to construct a recombinant that expressed the nucleocapsid gene of Lassa virus. Guineapigs immunised with the recombinant virus were protected against challenge with Lassa virus, whereas control animals showed the usual disease course, including pyrexia, anorexia, viraemia, and death. These data indicate not only that protective immunity to Lassa fever can be evoked by an experimental vaccine, but also that this response can be mediated by an internal protein component of the virus. PMID- 2885644 TI - AIDS in Africa. PMID- 2885645 TI - Immunopathology of schistosomiasis. PMID- 2885646 TI - The immune response in sarcoidosis. PMID- 2885647 TI - What doctors know about alcoholism. PMID- 2885648 TI - Social class differences in ischaemic heart disease in British men. AB - To examine why ischaemic heart disease (IHD) mortality rates in Britain are higher in manual than in non-manual workers 7735 middle-aged men in the British Regional Heart Study were followed up for 6 years, during which time 336 men experienced a major IHD event (fatal or non-fatal myocardial infarction or sudden cardiac death). The prevalence rates of IHD at screening, were higher in manual workers. Also, the attack rate of major IHD events during follow-up was 44% higher in manual workers. Marked differences in cigarette smoking contributed substantially to the increased risk of IHD in manual workers, who also had higher levels of blood pressure, were more obese, and took much less physical activity in leisure time. Adjustment for differences in these risk factors narrowed the gap between manual and non-manual workers in attack rates of IHD. Since the risk of IHD in Great Britain is high in all social classes, there would seem to be little justification for any overall policy for prevention of IHD to focus on social class. However, anti-smoking strategies might well take into account the social class differences described. PMID- 2885649 TI - Temporal relations between maternal rubella and congenital defects. AB - The Time relations between maternal rubella infection in pregnancy and the presence and type of defects in the children were determined from the records of 422 children with confirmed congenital rubella, registered in the National Congenital Rubella Surveillance Programme. In the 106 children born after laboratory-proven maternal infection, no defects were recorded following infection after the 17th week of pregnancy, but in the remaining 316 children defects followed infection reported to be as late as 33 weeks. The striking difference underlines the importance of serological investigation of pregnant women who present with a rash or a history of contact with rubella. With proven infection later than the 16th week the risk of fetal damage seems to be very small. Of 148 children followed up to school age, 40 (27%) attended normal schools. PMID- 2885650 TI - A controlled trial of weekly ultrasound therapy in chronic leg ulceration. AB - In a controlled trial to ascertain whether ultrasound given weekly in conjunction with a standard treatment for chronic leg ulcers improves the rate of healing 56 patients were randomised to standard treatment (paste impregnated bandage and a self-adhesive elastic bandage) and 52 to standard treatment plus pulsed ultrasound given weekly. After 12 weeks the proportion of ulcers healed was 20% greater in the ultrasound than in the control group. PMID- 2885651 TI - AIDS in Africa: misinformation and disinformation. PMID- 2885652 TI - Therapeutic risks in perspective. PMID- 2885653 TI - Rubella vaccination policy: a note of reassurance. PMID- 2885654 TI - Screening for cervical cancer. PMID- 2885655 TI - Splenectomy in Hodgkin's disease and second leukaemias. PMID- 2885656 TI - Tobacco-related deaths in China. PMID- 2885657 TI - Respiratory function and choice of antihypertensive agent. PMID- 2885658 TI - Ciprofloxacin for cholangitis. PMID- 2885659 TI - Skin colour, MPTP, and Parkinson's disease. PMID- 2885660 TI - Muscle G6PD deficiency. PMID- 2885661 TI - Physiological release of atrial natriuretic peptide in heart transplant recipient. PMID- 2885662 TI - Aztreonam in CAPD peritonitis. PMID- 2885663 TI - Benign cytomegalovirus mononucleosis in non-AIDS, HIV-infected patients. PMID- 2885664 TI - Immunosuppressants in treatment of patients with AIDS. PMID- 2885665 TI - Folate deficiency and demyelination in AIDS. PMID- 2885666 TI - Foscarnet-induced acute renal failure and effectiveness of haemodialysis. PMID- 2885667 TI - Release of histamine by H2-receptor antagonists? PMID- 2885668 TI - RU 486 administration in a child with Cushing's syndrome. PMID- 2885669 TI - Detection of sexual abuse in children. PMID- 2885670 TI - Efficacy and generic drugs. PMID- 2885671 TI - Molar units for drugs. PMID- 2885672 TI - Selenium in primary biliary cirrhosis. PMID- 2885673 TI - Diabetes in urban West Africans. PMID- 2885674 TI - Efficacy of recombinant DNA Plasmodium falciparum sporozoite vaccine? PMID- 2885676 TI - Errors in mortality statistics. PMID- 2885677 TI - Depression, stress, and immunity. PMID- 2885675 TI - Falciparum malaria probably acquired from infected skin-cut. PMID- 2885678 TI - Peptide neurotransmitters and myocardial ischaemia. PMID- 2885679 TI - An old treatment for mania. PMID- 2885680 TI - Lack of efficacy of plasma-exchange in removing antiphospholipid antibodies. PMID- 2885681 TI - Muscle contraction and tension headaches. PMID- 2885682 TI - Lowering blood pressure. PMID- 2885684 TI - Serum osmolality gap. PMID- 2885683 TI - Tetrahydrobiopterin and "non-responsive" dihydropteridine reductase deficiency. PMID- 2885685 TI - Haemodialysis-associated amyloidosis: differences in frequency between Europe and USA. PMID- 2885686 TI - Transient impairment of renal function and myoglobin turnover after generalised seizures. PMID- 2885687 TI - Dissecting cellulitis of the scalp: response to isotretinoin. PMID- 2885688 TI - Hyperbaric oxygen for carbon monoxide poisoning. PMID- 2885690 TI - Mentally incapable adults: consent to treatment. PMID- 2885689 TI - Human immunodeficiency virus and the law. PMID- 2885691 TI - Sensorineural hearing loss associated with Takayasu's disease. AB - This is a case report of sensorineural hearing loss associated with Takayasu's disease. Also known as "pulseless disease" and "aortic arch syndrome," Takayasu's disease involves narrowing of the aortic arch and its branches. Although the etiology is unknown, it is suspected to be an autoimmune disorder. In the case presented, steroid therapy resulted in an improvement of hearing. On one relapse the hearing loss worsened before the sedimentation rate increased. We speculate that the hearing loss is due to an autoimmune process or an ischemia involving the inner ear. We further speculate that hearing loss may indicate subsequent worsening of the disease. PMID- 2885692 TI - [Prognostically significant new territory in transplantation surgery]. PMID- 2885693 TI - [Myocardial infarct. Changes in diagnostic possibilities and therapeutic considerations in 25 years]. PMID- 2885694 TI - [Task and therapeutic success of after-care at a rehabilitation clinic of patients following an acute heart infarct]. PMID- 2885696 TI - [Diagnostic assessment of paroxysmal ventricular tachycardia and their clinical significance]. PMID- 2885695 TI - [Possibilities and experiences in heart surgery in patients over 70]. PMID- 2885697 TI - [Myocardial perforations in implantation of pacemaker electrodes. Where are right ventricular weak sites in the myocardium?]. PMID- 2885698 TI - [Sudden death in alcoholic cardiomyopathy]. PMID- 2885699 TI - [Comparative clinico-therapeutic study of gonadorelin and chorionic gonadotropin in boys with undescended testes]. PMID- 2885700 TI - Erythrocyte 3H-ouabain binding and digitalis treatment in ethanol addicted patients. AB - The binding of 3H-ouabain to human erythrocytes was analyzed in a population of hospitalized male ethanol addicted patients under long term digitalis treatment. In the non-alcoholic patient group the long term digitalis treatment induced an increase in Bmax and Kd values; such modification was not observed in the alcoholic patients. Chronic alcohol intake itself induced an increase in 3H ouabain kinetic parameters. These observations confirm that ouabain binding to human erythrocytes is subject to pharmacological and toxicological regulation and that adaptive changes in peripheral tissues can be useful in predicting possible parallel modifications in other less accessible tissues. PMID- 2885701 TI - Inhibition of rat prostate tumor growth by an octapeptide analog of somatostatin. AB - Analogs of a potent octapeptide analog of somatostatin (SRIF) H-(D)Phe-Cys-Tyr (D)Trp-Lys-Val-Cys-Thr(NH2) were synthesized. Aromatic substitutions for Tyr resulted in little change in inhibitory potency on growth hormone (GH) secretion in the rat. Substitutions for Val or (D)Trp resulted in analogs with diminished activity. Substitution of (D)Nal for (D)Phe increased duration of GH inhibition. Final weights of subcutaneously implanted prostate tumors (R3327) were 41% lower in rats treated with an N-terminal 4-chloro-(D)phenylalanyl analog as compared to vehicle treated controls. The analog had no effect on testicular weight or final plasma testosterone levels. SRIF analogs may represent an alternative treatment for prostate cancer that would be free of the untoward reproductive effects of other treatments (e.g. LH-RH or castration). PMID- 2885702 TI - A bromoacetylated analogue of cyanopindolol: an irreversible antagonist at rat beta-adrenoceptors. AB - A high affinity, chemically reactive cyanopindolol derivative. N8-bromoacetyl-N1 3'-(2-cyano-4-indolyloxy)-2'-hydroxypropyl-[Z]-1 ,8-diamino-p-menthane (Br-CYP) was synthesized and its interaction with beta-adrenoceptors characterized. Studies with rat heart, lung, brain, and red blood cell membranes indicated that the compound displaced 3H-dihydroalprenolol (3H-DHA) from beta-adrenoceptors with IC50 values in the nanomolar range. The concentration of functional beta adrenoceptors in membranes was markedly reduced when membranes were preincubated with Br-CYP and then extensively washed prior to assay. (+/-)Alprenolol and ( )isoproterenol, but not (+)isoproterenol, when included in the preincubation prevented this reduction in binding sites by Br-CYP. Br-CYP was active in vivo when injected intraperitoneally into rats. A dose of 10 micrograms/kg reduced the concentration of binding sites in membranes from heart by 30%, lung by 36%, and RBC by 70%, but did not affect sites on brain membranes 16 hours after injection. Higher doses blocked virtually all the 3H-DHA binding sites in the peripheral organs studied. Br-CYP reduced the concentration of beta-adrenoceptors in membranes from these same tissues (but not brain tissue) as long as two weeks after injection with recovery of binding occurring more rapidly in heart tissue than lung and red blood cells. These results suggest that Br-CYP may be a useful compound for in vivo studies of the biochemistry and pharmacology of beta adrenergic systems. PMID- 2885703 TI - New sensitive markers for the detection of experimental ascending pyelonephritis. AB - Kinetic parameters (Km and Vmax) of renal brush border membrane (BBM) enzymes alkaline phosphatase, maltase, leucine-aminopeptidase and gamma glutamyltranspeptidase were used as markers for the early detection of pyelonephritis. Km of all the enzymes studied remained unaltered. The Vmax of all the enzymes studied were found to be significantly decreased (p less than 0.05) 3 or 4 days postinfection and onwards in the left obstructed kidney. The Vmax of alkaline phosphatase and leucine-aminopeptidase was found to be significantly increased (p less than 0.05) in early stages and decreased (p less than 0.05) in later stages of infection in the right unobstructed kidney. No histopathological lesions confirming pyelonephritis could be seen 7 days postinfection in the left kidney and right kidney remained histopathologically unaltered. This demonstrated that BBM enzymes are much earlier disturbed as compared to histopathological changes. PMID- 2885704 TI - Ventromedial hypothalamic stimulation accelerates norepinephrine turnover in brown adipose tissue of rats. AB - To establish a functional link between the ventromedial hypothalamus (VMH) and brown adipose tissue (BAT), effects of electrical stimulation of the VMH and the lateral hypothalamus (LH) on norepinephrine (NE) turnover in the interscapular BAT were examined in rats. Stimulation of the VMH elicited about 3-fold increase in the rate of NE turnover in BAT, whereas stimulation of the LH had no appreciable effects. The effect of VMH stimulation was abolished after sympathetic ganglion blockade or by surgical sympathetic denervation of BAT. It was concluded that there is a sympathetic nerve-mediated connection between the VMH and BAT, and that stimulation of the VMH induces metabolic activation and heat production in BAT through an increase in sympathetic nerve activity. PMID- 2885705 TI - Noradrenergic effects on rat visual cortex: single-cell microiontophoretic studies of alpha-2 adrenergic receptors. AB - The catecholamine noradrenaline has been proposed to modulate the excitability of cortical neurons, and such a regulation may be mediated by specific adrenergic receptors. We characterized, using electrophysiological recordings, the types of responses of single cells in the rat visual cortex (areas 17 and 18) to the iontophoretic application of adrenergic agents. For the majority of spontaneous and visually-driven cells sampled, noradrenaline decreased the firing frequency, and in some cases of visually-driven cells could increase the signal/noise ratio. These effects were also documented after the application of the alpha-2 adrenergic agonists clonidine and oxymetazoline, and could be reduced or blocked by a previous ejection of the specific alpha-2 antagonist idazoxan. The present study supports a role for alpha-2 adrenoceptors in the modulation of sensory inputs to the visual cortex. PMID- 2885706 TI - Nucleus tractus solitarius: an evaluation by in vivo voltammetry. AB - Nucleus tractus solitarius (NTS) is a brainstem nucleus known to play an important role in baroreceptor mediated cardiovascular regulation. As part of our study of the role of monoamines in the function of NTS, we have characterized pharmacologically the in vivo electrochemical signal recorded from the nucleus using carbon paste electrodes and linear sweep voltammetry with semiderivative signal processing in awake, freely moving rats. Two peaks were recorded by these techniques, one at 0.14 V and a second at 0.28 V. The tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine led to a significant reduction in the peak recorded at 0.14 V whereas it had no effect on the higher potential peak at 0.28 V. The dopamine-beta-hydroxylase inhibitor fusaric acid resulted in a large reduction in the 0.14 V peak and led to a 30% increase in the 0.28 V peak height. Pargyline, a monoamine oxidase inhibitor, did not change the low potential peak but did significantly reduce the 0.28 V peak. Tissue assays provided further support for the interpretation of in vivo electrochemical recordings. Norepinephrine concentration was reduced with fusaric acid. Tissue serotonin was not affected by any of the drugs while the 5-HIAA content was increased with fusaric acid and reduced with pargyline. These experimental findings lead to the conclusion that the first peak in the voltammogram most likely represents norepinephrine with a possible contribution by dopamine but not by DOPAC. The second peak appears to be 5-HIAA. PMID- 2885707 TI - Effects of barbiturates on the inhibitory action of GABA on excitatory response of the stomach to stimulation of vagal afferent fibers in cat. AB - Effects of barbiturates on the inhibitory action of GABA to the hexamethonium resistant excitatory response of the stomach to stimulation of the vagal afferent fibers were studied in cats. Inhibition of the hexamethonium-resistant excitatory response by GABA were compared under alpha-chloralose, alpha-chloralose phenobarbital (PhB), and alpha-chloralose-pentobarbital (PB)-anesthesia in cats. The ID50 of GABA on the hexamethonium-resistant excitatory response was not significantly affected by PhB, but reduced by PB. Both picrotoxin and bicuculline antagonized the effects of GABA. The present experiments demonstrated that PB potentiated the inhibitory effect of GABA on the hexamethonium-resistant excitatory response of the stomach, and suggested that the potentiation by PB may be due to activation of GABA-receptor-ionophore complex. PMID- 2885708 TI - The in vitro release of immunoreactive dynorphin and alpha-neoendorphin from the perfused rat duodenum. AB - The release of immunoreactive (ir) dynorphin (DYN) and alpha-neoendorphin (ir ANEO) from the isolated perfused rat duodenum was demonstrated using specific radioimmunoassays (RIAs). Depolarization of the tissue by increasing the potassium (K+) concentration up to 108 mM enhanced the release of ir-DYN and ir ANEO in Ca2+-dependent manner. Administration of the serotonin-releasing agent fenfluramine (10(-6) M) and the serotonin receptor agonist m chlorophenylpiperazine (m-CPP, 10(-6) M) stimulated the release of ir-DYN and ir ANEO from the duodenum. A subsequent study revealed that serotonin (5-HT, 10(-6) 10(-4) M) induced a dose-dependent increase in the release of ir-DYN and ir-ANEO from the duodenum. The effect of 5-HT on the release of ir-DYN and ir-ANEO from the duodenum was antagonized by 5-HT antagonist cyproheptadine (10(-6) M). The presence of dynorphin and the related peptides in the gastrointestinal tract (GIT) and their release from the duodenum in vitro indicate that these peptides may act as transmitters involved in some GIT functions. Furthermore, our results suggest that at least part of 5-HT effects on the GIT may be mediated by the release of dynorphin and the related peptides. PMID- 2885709 TI - Intracellular free calcium in rat anterior pituitary cells monitored by fura-2. AB - Rat anterior pituitary cells, loaded with the calcium indicator dye fura-2 after primary culture, were challenged with prolactin and growth hormone secretagogues and inhibitory hormones. To initially validate the technique, the calcium channel activator maitotoxin effectively increased intracellular free calcium [( Ca++]i). Various concentrations of the secretagogues thyrotropin releasing hormone or angiotensin II induced peak increases in [Ca++]i within 15 sec, followed by a lower and prolonged plateau phase. The inhibitory hormones dopamine and somatostatin maximally reduced [Ca++]i by 15-20 sec, followed by a spontaneous return to baseline over 5-10 min. The receptor antagonists saralacin and spiperone blocked the angiotensin II and dopamine effects, respectively. Thus, fura-2 appears to be an adequate probe for resolving second-to-second changes in [Ca++]i induced by hormone receptor activation in anterior pituitary cells. PMID- 2885710 TI - Extrapancreatic effects of L-leucine infusion in leucine-sensitive and control subjects. AB - We studied the extrapancreatic effects of L-leucine infusion (2.5 mumol/kg/min) in six controls (three females, three males) and three members of a family with leucine-sensitive hypoglycemia (LSH). Total glucose disposal and endogenous glucose production (EGP) rates were assessed after an overnight fast (12 to 14 hour) during somatostatin (SRIF) infusion (500 micrograms/h) with insulin replacement (0.2 mU/kg/min), combined with D-(3-3H)-glucose infusion. Additional studies of forearm arterial-venous (A-V) balances of amino acids, glucose, and other substrates, combined with L-(1-14C)-leucine kinetics, were done in these two groups. L-leucine infusion resulted in a 15% decrease in whole-body total glucose utilization in controls (P less than .05) during SRIF-insulin infusion, but did not affect glucose utilization in LSH subjects. EGP was not affected by L leucine infusion in either group. Control subjects demonstrated a significant reduction in forearm glucose uptake and greater lactate release during L-leucine infusion, compared to the basal state. In contrast, subjects with LSH showed a slight increase in forearm glucose uptake and significantly less lactate release during L-leucine infusion. Subjects with LSH demonstrated significantly lower forearm leucine uptake, and lower rates of appearance and oxidation of L-(1-14C) leucine during leucine infusion, compared to controls. Our data suggest that members of this LSH kindred have a defect in intracellular leucine metabolism in skeletal muscle, resulting in a lack of leucine-induced inhibition of glucose utilization. This may contribution to the development of hypoglycemia in these subjects. PMID- 2885712 TI - Covalent attachment of oligosaccharide-asparagine derivatives: incorporation into glutamine residues with the enzyme transglutaminase. PMID- 2885713 TI - Enzymatic diagnosis of sphingolipidoses. PMID- 2885711 TI - Desensitization of the thyroid cyclic AMP response to thyroid stimulating immunoglobulin: comparison with TSH. AB - Studies were conducted to examine the characteristics of thyroid cell cAMP stimulation by thyroid stimulating immunoglobulins (TSI) and to compare the cAMP response to TSI and TSH in desensitized human thyroid cells. In terms of cAMP production, preexposure (eight hours) of the cells to TSI induced a desensitization very similar to TSH-induced desensitization: both TSH- and TSI desensitized cells showed a normal response to cholera toxin and forskolin stimulation; TSH and TSI desensitization was interchangeable in that desensitization by either stimulator affected the action of the other; the time of recovery from either TSH and TSH desensitization was identical; the cycloheximide (10(-4) mol/L) prevented both TSI- and TSH-induced desensitization; preexposure of the cells to iodine, which affects mainly the adenylate cyclase catalytic unit, or to epinephrine, which activate the inhibitory regulatory protein Ni by the alpha 2-adrenergic stimulation, induced a similar inhibition of the subsequent stimulation by both TSH or TSI. The remarkable similarities between TSH and TSI in stimulating and desensitizing thyroid cells strongly support the concept that TSI activates thyroid adenylate cyclase by interacting with the TSH receptor and not through an allosteric mechanism. PMID- 2885714 TI - Activator proteins for lysosomal glycolipid hydrolysis. PMID- 2885715 TI - Neurotransmitter-stimulated inositol phosphate accumulation in hippocampal slices. AB - The agonist-induced accumulation of [3H]IP in the presence of lithium represents a sensitive method for studying a number of receptor-mediated events in brain. In the presence of lithium, receptor-mediated [3H]IP3 formation in brain is difficult to demonstrate. It is possible that lithium itself may prevent the formation if IP3 and, thus, the presence of lithium in the incubation may account for such a discrepancy. It is likely that the effects of lithium on the PI cascade are more complex then previously envisioned. The recent identification of the inositol polyphosphates, myo-inositol 1,3,4-trisphosphate and myo-inositol 1,3,4,5-tetrakisphosphate, indicates that other inositol phosphates need to be considered in future studies of receptor-mediated PI metabolism. PMID- 2885716 TI - Cathepsin T. PMID- 2885717 TI - Phenylalanine 4-monooxygenase from Chromobacterium violaceum. PMID- 2885718 TI - Tyrosine 3-monooxygenase from bovine adrenal medulla. PMID- 2885719 TI - Tyrosine 3-monooxygenase from rat adrenals. PMID- 2885720 TI - Tyrosine 3-monooxygenase from rat pheochromocytoma. PMID- 2885721 TI - Restriction fragment length polymorphisms. PMID- 2885724 TI - Lack of correlation between fibrils, hydrophobicity and adhesion for strains of Streptococcus sanguis biotypes I and II. AB - Fifteen strains of Streptococcus sanguis biotype I and eight strains of Streptococcus sanguis biotype II with peritrichous fibrils, tufts of fibrils or a mixture of fibrils and fimbriae on the cell surface, were tested for their ability to adhere to saliva coated spheroidal hydroxyapatite (S-SHA) in a radiolabelled assay. S. sanguis I strains adhered better than S. sanguis II strains and peritrichously fibrillar strains generally adhered better than tufted strains. There was no correlation between the density of fibrillation and adhesion. The only highly adherent strain of S. sanguis II carried fimbriae in addition to fibrils. No correlation was observed between cell surface hydrophobicity as measured by phase partitioning with hexadecane and adhesion to S-SHA. PMID- 2885723 TI - Genetic and molecular mapping of the pma1 mutation conferring vanadate resistance to the plasma membrane ATPase from Saccharomyces cerevisiae. AB - In the yeast Saccharomyces cerevisiae, the pma1 mutations confers vanadate resistance to H+-ATPase activity when measured in isolated plasma membranes. In vivo, the growth of pma1 mutants is resistant to Dio-9, ethidium bromide and guanidine derivatives. This phenotype was used to map the pma1 mutation adjacent to LEU1 gene on chromosome VII. From a cosmid library of a wild-type Saccharomyces cerevisiae genome, a large 30 kb DNA fragment was isolated by complementation of a leu1-pma1 double mutant. A 5kb HindIII fragment was subcloned and it restored both Leu+ and Pma+ phenotypes after integrative transformation. The restriction map of the 5 kb HindIII fragment and Southern blot analysis reveal that the cloned fragment contains the entire structural gene for the plasma membrane ATPase and the 5' end of the adjacent LEU1 gene. The pma1 mutation conferring vanadate-resistance is thus located in the structural gene for the plasma membrane ATPase. PMID- 2885722 TI - Nuclear and mitochondrial revertants of a mitochondrial mutant with a defect in the ATP synthetase complex. AB - Yeast strain 990 carries a mutation mapping to the oli1 locus of the mitochondrial genome, the gene encoding ATPase subunit 9. DNA sequence analysis indicated a substitution of valine for alanine at residue 22 of the protein. The strain failed to grow on nonfermentable carbon sources such as glycerol at low temperature (20 degrees C). At 28 degrees C the strain grew on nonfermentable carbon sources and was resistant to the antibiotic oligomycin. ATPase activity in mitochondria isolated from 990 was reduced relative to the wild-type strain from which it was derived, but the residual activity was oligomycin resistant. Subunit 9 (the DCCD-binding proteolipid) from the mutant strain exhibited reduced mobility in SDS-polyacrylamide gels relative to the wild-type proteolipid. Ten revertant strains of 990 were analyzed. All restored the ability to grow on glycerol at 20 degrees C. Mitotic segregation data showed that eight of the ten revertants were attributable to mitochondrial genetic events and two were caused by nuclear events since they appeared to be recessive nuclear suppressors. These nuclear mutations retained partial resistance to oligomycin and did not alter the electrophoretic behavior of subunit 9 or any other ATPase subunit. When mitochondrial DNA from each of the revertant strains was hybridized with an oligonucleotide probe covering the oli1 mutation, seven of the mitochondrial revertants were found to be true revertants and one a second mutation at the site of the original 990 mutation. The oli1 gene from this strain contained a substitution of glycine for valine at residue 22. The proteolipid isolated from this strain had increased electrophoretic mobility relative to the wild-type proteolipid. PMID- 2885725 TI - Biochemical studies on acetate non-utilizing mutants of Aspergillus terreus IRRL 16043. AB - The strain Aspergillus terreus IRRL 16043 can utilize glucose as well as acetate as a sole carbon source. Thirty-nine mutants were isolated from the wild-type by treatment with a chemical mutagen, N-methyl-N'-nitro-N-nitrosoguanidine (MNTG) which could not utilize acetate as a sole carbon source, and were designated as acetate non-utilizing (acu). By complementation and biochemical analyses they were divided into three functional groups, acu A, acu B and acu C lacking isocitrate lyase, malate synthase and acetyl-CoA synthetase activity, respectively. PMID- 2885726 TI - Surface haemagglutinating activity of Pseudomonas aeruginosa. AB - Intact cells of several strains of Pseudomonas aeruginosa agglutinate papain treated human erythrocytes. The agglutinating activity appears to reside in the surface layers of the bacterium-Pseudomonas surface haemagglutinin. This activity does not correlate with the existence of the internal PA-I and PA-II lectins, the presence of fimbriae or adherence to human buccal epithelial cells. Disruption of the bacterial cells by sonication abolishes their haemagglutinating activity. The intact cells of P. aeruginosa are also able to agglutinate rabbit, chicken, dog, guinea pig and sheep erythrocytes. This activity is generally higher with papain treated erythrocytes, except those of rabbit in which lower haemagglutinating activity is observed after papain treatment. Optimal conditions for the haemagglutination are 37 degrees C and pH 6-7. Simple sugars do not inhibit, while fetuin and hydrophobic amino acids inhibit this activity. Exposure of the bacterial cells to proteolytic enzymes, EDTA or denaturating conditions abolish the haemagglutinating activity. These results indicate that the surface haemagglutinin is a protein which agglutinates red blood cells via hydrophobic interactions. PMID- 2885727 TI - Detection of cross-reactive antibody to BLV p24 in sera of human patients infected with HTLV. AB - For detection of antibody to bovine leukemia virus (BLV) major core protein of p24 and cross-reactive antibody in human patients infected with human T cell leukemia virus type I (HTLV-I), monoclonal antibody, D432 against BLV p24 was used by competitive binding enzyme-linked immunoadsorbed assay (ELISA). In sera from cattle with enzootic bovine leukosis (EBL) which were positive for BLV antibodies by immunodiffusion test, 109 out of 112 (97.3%) were positive for BLV p24 antibody by competitive binding ELISA. By using the same procedures, 21 samples from adult T cell leukemia (ATL) patients and healthy carriers with HTLV I were tested for cross-reactive antibody to BLV p24. All 21 samples were positive for HTLV-I antibodies by immunofluorescence test and/or ELISA. By competitive binding ELISA using non-treated BLV antigens, none of these 21 samples inhibited the binding of the D432. When the BLV antigen was treated by several different denaturation procedures, several HTLV-I positive samples showed the inhibition of the D432 binding and the most effective treatment was by 2 mercaptoethanol (2-ME). Sixteen out of 21 samples showed the presence of cross reactive antibody against 2-ME-treated BLV antigens. The cross-reactivity of human sample to BLV p24 antigen was further confirmed by Western blotting of the 2-ME-treated BLV antigens. None of the 28 samples from leukemia patients other than ATL which were negative for HTLV-I antibodies showed inhibition of the D432 by the competitive binding ELISA. PMID- 2885728 TI - The impact of molecular biology on the practice of medicine. Part 2. Diagnostics, therapeutics and ethics. PMID- 2885729 TI - Drugs that cause sexual dysfunction. PMID- 2885730 TI - Ipratropium. PMID- 2885731 TI - [Experience with the use of mermithids to control bloodsucking mosquitoes in Tadzhikistan]. PMID- 2885732 TI - [Clinicopathologic conference. Prolactinoma and hyperaldosteronism in a 55-year old male: variant of multiple endocrine adenomatosis (MEA) type I?]. PMID- 2885734 TI - Relationship between receptor occupancy and response at striatal dopamine autoreceptors. AB - The irreversible dopamine (DA) receptor antagonist N-ethoxy-carbonyl-2-ethoxy-1,2 dihydroquinoline (EEDQ) was used to determine the extent of receptor reserve at DA autoreceptors regulating in vivo tyrosine hydroxylase activity. Rats were treated with vehicle or EEDQ (1 X 0.5-2 X 6 mg/kg, subcutaneously) and, 24 hr later, dose response curves were generated for DA agonist reversal of gamma butyrolactone-induced striatal L-3,4-dihydroxyphenylalanine (L-DOPA) accumulation. Double reciprocal plots were obtained of equieffective doses of agonist required to elicit response at several levels of effect before and after partial irreversible receptor inactivation. A pseudo-dissociation constant (pseudo-KA, in units of dose) and the fraction of receptors remaining active (q) were determined; these values were then used to calculate the relationship between receptor occupancy and response. The ED50 (1 microgram/kg) for the full DA receptor agonist N-propylnorapomorphine (NPA) was shifted 2.8, 4.8-, and 11.3 fold to the right after partial irreversible receptor blockade which left the fraction of receptors remaining active (q) at 0.37, 0.17 and 0.058, respectively. Corresponding maximal reversal of L-DOPA accumulation was 100, 77, and 58%, indicating a nonlinear relationship between receptor occupancy and response for NPA and the presence of a large receptor reserve; maximal and half-maximal responses were calculated to require occupancy of 30 and 3.8% of the total receptor pool, respectively. Dose response curves were also obtained for the DA autoreceptor-selective agents EMD 23,448 and (+)- and (-)-3-PPP before and after EEDQ treatment. In controls, EMD 23,448 and (+)-3-PPP, like NPA, completely reversed striatal gamma-butyrolactone-induced L-DOPA accumulation, whereas the maximal effect of (-)-3-PPP was 52% reversal. After EEDQ treatment (6 mg/kg), EMD 23,448 and (+)-3-PPP showed relatively small shifts in ED50 values. Furchgott analysis demonstrated that all three atypical agents are partial agonists at the DA autoreceptor with efficacies of 0.19 (EMD 23,448), 0.12 [(+)-3-PPP], and 0.05 [(-)-3-PPP] relative to NPA. The presence of a larger receptor reserve at pre versus postsynaptic D2 DA receptors and the partial agonist character of drugs such as EMD 23,448 and the enantiomers of 3-PPP may account for their autoreceptor selectivity. PMID- 2885735 TI - Calmodulin may play a pivotal role in neurotransmitter-mediated inhibition and stimulation of rat cerebellar adenylate cyclase. AB - Adenylate cyclase activity was stimulated 2.5-fold by exogenous Ca2+/calmodulin (CaM) (1 microM) in rat cerebellar plasma membranes which had been depleted of endogenous Ca2+/CaM. In EGTA-washed membranes, phenylisopropyladenosine (an adenosine receptor agonist) was unable to inhibit adenylate cyclase activity unless exogenous Ca2+/CaM was included in the assay. Conversely, isoproterenol (a beta-adrenergic receptor agonist) was able to stimulate adenylate cyclase activity only in the absence of Ca2+/CaM. The regulation of adenylate cyclase activity by guanyl-5'-yl-imidodiphosphate [Gpp(NH)p, a nonhydrolyzable guanine nucleotide analog, used to monitor interactions between guanine nucleotide binding proteins and the catalytic unit of adenylate cyclase] was similar to that of phenylisopropyladenosine and isoproterenol; i.e., Gpp(NH)p produced inhibition exclusively in the presence of Ca2+/CaM, whereas only stimulation was observed in the absence of Ca2+/CaM. These results suggest that changes in intracellular Ca2+ concentrations may determine whether adenylate cyclase can be stimulated or inhibited by neurotransmitters. PMID- 2885733 TI - Ameba-bacterium relationship in amebiasis. PMID- 2885736 TI - Interactions between adenosine and alpha 1-adrenergic agonists in regulation of respiration in hamster brown adipocytes. AB - Respiration in brown adipocytes can be increased by beta-adrenergic receptor agonists or by alpha 1-adrenergic receptor agonists (phenylephrine and norepinephrine). Previous studies have shown that beta receptor-stimulated respiration is inhibited by adenosine and that enzymatic removal of adenosine produced by fat cells under normal incubation conditions enhances the respiratory response to beta receptor activation. The present experiments were performed to determine the effect of adenosine on the respiratory response elicited by agonists of alpha 1 receptors. The alpha-adrenergic agonists phenylephrine and norepinephrine (in the presence of the beta-adrenergic antagonist propranolol) stimulated respiration and the respiratory response to each agent was enhanced when endogenous adenosine was removed with adenosine deaminase. Addition of hydrolysis-resistant analogues of adenosine inhibited phenylephrine-stimulated respiration, and, since N6-phenylisopropyladenosine was more effective than was 5'-N-ethylcarboxamidoadenosine, we conclude that an A1 receptor is involved. In contrast, the P site agonist 2',5'-dideoxyadenosine did not inhibit phenylephrine stimulated respiration but did cause some inhibition of isoproterenol-stimulated respiration. These results suggest that adenosine, acting via A1 receptors, modulates alpha 1-adrenergic effects on thermogenesis in brown fat cells, an action that is analogous to its inhibition of beta-adrenergic receptor-stimulated thermogenesis. PMID- 2885737 TI - The relationship between alpha 1-adrenergic receptor occupancy and response in BC3H-1 muscle cells. AB - The relationship between alpha 1-adrenergic receptor occupancy by agonists or antagonists and the regulation of intracellular Ca2+ was examined. Receptor occupancy was measured using the antagonist [3H]prazosin and correlated with agonist-elicited 45Ca2+ fluxes. The agonists epinephrine (E), norepinephrine (NE), and phenylephrine (PE) coordinately activated Ca2+ efflux, reflecting a substantial mobilization of intracellular Ca2+, as well as a smaller 45Ca2+ influx. The agonist concentration dependences for influx and efflux were similar, with the order of potency expected for alpha 1 receptors (E greater than or equal to NE greater than PE). To determine the relationship between receptor occupancy and response, the slowly dissociating antagonist prazosin was used to inactivate specified fractions of the receptor population. A linear relationship was observed between the remaining activatable receptors and residual 45Ca2+ efflux elicited by E or NE, except at saturating agonist concentrations where some curvature was observed. Moreover, the concentration dependence for agonist elicited 45Ca2+ efflux was shifted toward slightly higher concentrations of E or NE following prazosin inactivation. These results suggest the presence of a modest receptor reserve which is revealed by E or NE, but not by PE. Agonist occupation was measured over the same interval as receptor activation by competition with the initial rate of [3H]prazosin association. All three agonists exhibited the major fraction of receptor occupation over the same concentration ranges required for the functional response. Exposure of receptors to specified agonist concentrations for 30 min had little effect on the number of receptors or their ligand affinities, whereas a 2.5-hr exposure to agonist decreased apparent agonist affinity as well as the number of receptors recognized by [3H]prazosin. PMID- 2885738 TI - Evidence that cGMP is the mediator of endothelium-dependent inhibition of contractile responses of rat arteries to alpha-adrenoceptor stimulation. AB - Endothelium-derived relaxing factors (EDRFs) have been previously shown to exert an inhibitory influence on the contractile effects of alpha-adrenoceptor agonists in vascular smooth muscle. alpha 2-Adrenoceptor agonists such as clonidine have been reported to be particularly susceptible to this effect, and it has been suggested that clonidine acts on alpha 2 receptors on endothelial cells to stimulate the release of EDRF. EDRF release is known to be accompanied by increased levels of cGMP in many blood vessels, and it is suggested that cGMP exerts an inhibitory influence on the smooth muscle cells, which tends to counteract the contractile effect of the clonidine. This hypothesis was tested in isolated rings of rat aorta and mesenteric artery using the cGMP lowering agent, 6-anilino-5,8-quinolinedione (LY83583). LY83583 markedly decreased resting levels of cGMP in these vascular preparations and completely prevented both the relaxation and the cGMP elevation normally caused by acetylcholine in rat aorta with intact endothelium. These effects of LY83583 are identical to those observed after mechanical disruption of the endothelium. LY83583 also enhanced the contractile responses to norepinephrine and particularly to clonidine in both aorta and mesenteric artery. The effects of LY83583 on contractile responses to both alpha-adrenoceptor agonists were reversed by low concentrations of 8-bromo cGMP. Clonidine did not increase cGMP levels in vascular preparations with intact endothelia, in the presence or absence of LY83583. Thus, enhanced release of EDRF by clonidine did not appear to be responsible for the inhibition of its contractile effects observed in the presence of intact endothelial cells. Our results suggest instead that this endothelium-dependent inhibition is due to spontaneous release of EDRF, which results in tonic elevation of cGMP in the vascular smooth muscle. This tonic elevation of cGMP exerts a more marked inhibitory effect against contractions induced by the partial agonist, clonidine, than it does against contractions induced by a full agonist, norepinephrine. PMID- 2885739 TI - Tight agonist binding may prevent the correct interpretation of agonist competition binding curves for alpha 2-adrenergic receptors. AB - alpha 2-Adrenergic receptors in calf retina membranes can be specifically labeled with the tritiated antagonist 3H-RX 781094. Saturation binding occurs to a single class of noncooperative sites. The number of sites amounts to 1070 +/- 243 and 935 +/- 178 fmol/mg of protein, and the equilibrium dissociation constants equal 1.8 +/- 0.4 and 3.8 +/- 0.3 nM at 25 degrees and 37 degrees, respectively. Binding is rapid, equilibrium being reached within 5 min, and is reversible. At both temperatures, (-)-epinephrine competition binding curves are shallow in the presence of magnesium ions. The curves, obtained for incubation periods varying between 5 and 60 min, are superimposable at 37 degrees. Computer-assisted analysis indicates that approximately 75% of the receptors (RH sites) display high agonist affinity for (-)-epinephrine as well as for the other agonists tested: (-)-norepinephrine, clonidine, and UK 14304. However, the (-)-epinephrine competition curves display a time-dependent leftward shift at 25 degrees. This can be attributed to an increase in agonist affinity for the RH sites. Addition of 0.1 mM Gpp(NH)p causes a marked steepening and rightward shift of the curves, at both 25 and 37 degrees. These curves are superimposable for all of the incubation times tested. The nonequilibrium of agonist competition binding at 25 degrees can be attributed to slow dissociation of the agonist (i.e., tight binding) when the receptor is coupled to the regulatory component Ni. This dissociation rate can be measured by preincubation of the membranes with 10 microM (-)-epinephrine, followed by extensive washing and incubation with 3H-RX 781094 for increasing lengths of time. The first order rate of agonist dissociation (i.e., receptor recovery) is appreciably faster at 37 degrees than at 25 degrees: i.e., 0.029 min-1 and 0.0044 min-1, respectively. These findings are confirmed by kinetic experiments using the radiolabeled agonist 3H-UK 14304. Slow agonist dissociating kinetics may prevent the correct evaluation of the agonist binding parameters by computerized analysis of competition binding curves when the incubation time is too short, especially at low temperature. PMID- 2885740 TI - Use of the Escherichia coli gene for asparagine synthetase as a selective marker in a shuttle vector capable of dominant transfection and amplification in animal cells. AB - A new dominant amplifiable selective system for use in bacterium-animal cell shuttle vectors was developed by the insertion of a 2-kilobase genomic fragment containing the cloned Escherichia coli gene for asparagine synthetase (AS) into the pBR322-simian virus 40 recombinant vector pSV2 so as to place the translational initiator codon for the bacterial AS about 1,000 base pairs downstream from the simian virus 40 early promoter. This new construct, pSV2-AS, retains bacterial sequences for transcriptional and translational initiation and so can express AS in bacteria. The construct can also complement AS- mutants of mammalian cells, giving AS+ transfectants capable of growth in medium lacking asparagine, with relatively high efficiency (about 300 colonies per microgram of DNA per 10(6) cells exposed). The vector can be amplified up to 100-fold in such AS+ transfectants by selection in asparagine-free medium containing increasing concentrations of the AS inhibitor beta-aspartyl hydroxamate. AS+ transfectants were found to be much more resistant to a second AS inhibitor, Albizziin, than were normal AS+ animal cell lines. This difference, which may indicate a strong resistance of the bacterial AS enzyme to Albizziin, was exploited to develop an effective selection for bacterial AS transfectants of a number of wild-type AS+ cell lines of rat, Chinese hamster, mouse, and human origin. LR-73 cells, a Chinese hamster AS+ cell line, were transfected with pSV2-AS with an efficiency of about 1,000 colonies per 0.5 microgram of DNA per 10(6) cells. The integrated construct in these cells was amplified by incubation of the transfectants in increasing concentrations of beta-aspartyl hydroxamate. Advantages and disadvantages of this new dominant, selectable, and amplifiable marker over markers commonly used in shuttle vectors are discussed. PMID- 2885741 TI - Characterization of nit-2, the major nitrogen regulatory gene of Neurospora crassa. AB - The nit-2 gene is the major nitrogen-regulatory gene of Neurospora crassa, and under conditions of nitrogen limitations, it turns on the expression of various unlinked structural genes which specify nitrogen-catabolic enzymes. The nit-2 gene was subcloned as a 6-kilobase (kb) DNA fragment from a cosmid that carried approximately a 40-kb N. crassa DNA insert. The nit-2 gene was localized in a DNA segment of approximately 3.5 kb and was shown to correspond to a unique DNA sequence located on linkage group 1. Several N. crassa nit-2 transformants were characterized and were found to possess significantly different levels of the regulated enzyme nitrate reductase. Northern blot analysis of RNA from various strains was carried out to determine whether the nit-2 gene was expressed constitutively or was itself subject to regulation. The results revealed that the nit-2 gene is transcribed to give a single large mRNA of approximately 3.5 kb. Expression of the nit-2 gene is regulated such that its transcript is present at a substantially higher level in cells which are limited for nitrogen than in cells growing under nitrogen-repressed conditions. However, the nit-2 gene is not controlled by autogenous regulation. The nit-2 gene was transcribed only at a low level in nmr-1 and in gln-1b, under both nitrogen-repressed and derepressed conditions, suggesting that these unlinked loci may exert a positive regulatory effect on nit-2. PMID- 2885742 TI - Characterization of an episome produced in hamster cells that amplify a transfected CAD gene at high frequency: functional evidence for a mammalian replication origin. AB - In a previous study (G. M. Wahl, B. Robert de Saint Vincent, and M. L. De Rose, Nature (London) 307:516-520, 1984), we used gene transfer of a CAD cosmid to demonstrate that gene position profoundly affects amplification frequency. One transformant, T5, amplified the donated CAD genes at a frequency at least 100 fold higher than did the other transformants analyzed. The CAD genes in T5 and two drug-resistant derivatives were chromosomally located. In this report, we show that a subclone of T5 gives rise to an extrachromosomal molecule (CAD episome) containing the donated CAD genes. Gel electrophoresis indicated that the CAD episome is approximately 250 to 300 kilobase pairs, and a variety of methods showed that it is a covalently closed circle. We show that the CAD episome replicates semiconservatively and approximately once per cell cycle. Since the CAD cosmid, which comprises most of the CAD episome, does not replicate autonomously when transfected into cells, our results indicate that either the process which generated the episome resulted in a cellular origin of DNA replication being linked to the CAD sequences or specific rearrangements within the episome generated a functional origin. The implications of these results for mechanisms of gene amplification and the genesis of minute chromosomes are discussed. PMID- 2885743 TI - Transcriptional regulation of the human CAD gene during myeloid differentiation. AB - CAD codes for a trifunctional protein involved in the catalysis of the first three enzymatic activities in the de novo pyrimidine biosynthetic pathway, namely, carbamoyl-phosphate synthetase II (EC 6.3.5.5), aspartate transcarbamylase (EC 2.1.3.2), and dihydroorotase (EC 3.5.2.3). CAD regulation was studied in the human promyelocyte leukemic line HL-60 as it differentiated into monocytic or granulocytic lineages after induction by 12-O tetradecanoylphorbol-13-acetate or trans-retinoic acid and dibutyryl cyclic AMP, respectively. Within 12 h of induction of HL-60 cells with either inducer, total cellular levels of CAD RNA essentially disappeared. On the other hand, no apparent decreases in beta-actin RNA levels were seen even 48 h after HL-60 cells were induced, as compared with untreated cells. With nuclear runoff assays, it was clearly shown that the inactivation of CAD gene expression during the induction of HL-60 cells with either inducer was at the transcriptional level. The nuclear runoff experiments also demonstrated that the CAD gene expression was shut down in less than 4 h after induction, well before morphological changes were observed in these cells. At the enzymatic level, the activity of aspartate transcarbamylase, one of the three enzymes encoded by the CAD gene, decreased by about half within 24 h of induction, suggesting a CAD protein half-life of 24 h in differentiating HL-60 cells. Nevertheless, this means that significant levels of aspartate transcarbamylase activity remained even after the cells have stopped proliferating. From the RNA data, it is clear that CAD gene expression is rapidly turned off as promyelocytes begin to terminally differentiate into macrophages and granulocytes. We suspect that the inactivation of the CAD gene in induced HL 60 cells is a consequence of the differentiating cells leaving the cell cycle and becoming nonproliferating. PMID- 2885745 TI - Social phobia. PMID- 2885746 TI - Panic disorders. PMID- 2885744 TI - DNA sequences homologous to the Drosophila opa repeat are present in murine mRNAs that are differentially expressed in fetuses and adult tissues. AB - A mouse embryonic cDNA containing two opa-like (CAX)n repeats was isolated on the basis of its cross-hybridization with a Drosophila K10 cDNA. Such repeated sequences were present in different murine mRNAs, some of which were specifically expressed during fetal life or in different adult tissues. This suggests that, as already described for Drosophila, opa-like sequences are parts of proteins involved in ontogenic or cell-type-specific functions in vertebrates. However, unlike Drosophila, such repeated sequences were not found within the murine homeo boxes containing genes of the Hox-1 complex. PMID- 2885747 TI - Cardiovascular effects of opioid anesthesia. PMID- 2885748 TI - Anesthetic interactions with beta-blockers and calcium channel blockers. PMID- 2885749 TI - Anesthesia for the aged: some pharmacokinetic and pharmacodynamic considerations. PMID- 2885750 TI - Nonspecific aortitis and large-vessel arteritis in a 16-year-old girl: CT and angiographic diagnosis. PMID- 2885751 TI - Methods of creative cognition in medical diagnosis. PMID- 2885752 TI - Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells. AB - Glutamate is taken up avidly by glial cells in the central nervous system. Glutamate uptake may terminate the transmitter action of glutamate released from neurons, and keep extracellular glutamate at concentrations below those which are neurotoxic. We report here that glutamate evokes a large inward current in retinal glial cells which have their membrane potential and intracellular ion concentrations controlled by the whole-cell patch-clamp technique. This current seems to be due to an electrogenic glutamate uptake carrier, which transports at least two sodium ions with every glutamate anion carried into the cell. Glutamate uptake is strongly voltage-dependent, decreasing at depolarized potentials: when fully activated, it contributes almost half of the conductance in the part of the glial cell membrane facing the retinal neurons. The spatial localization, glutamate affinity and magnitude of the uptake are appropriate for terminating the synaptic action of glutamate released from photoreceptors and bipolar cells. These data challenge present explanations of how the b-wave of the electroretinogram is generated, and suggest a mechanism for non-vesicular voltage dependent release of glutamate from neurons. PMID- 2885753 TI - Loss of alleles of loci on the short arm of chromosome 3 in renal cell carcinoma. AB - Loss of genes at specific chromosomal loci is a characteristic of retinoblastoma, Wilms' tumour, transitional cell carcinoma of the bladder, embryonal tumours and small cell carcinoma of the lung. The significance of nonrandom gene loss in these neoplasms is that gene loss on one chromosome may uncover null mutations at corresponding loci of the homologous chromosome. Loss of specific gene products from somatic cells may be critical in the origin or evolution of certain human tumours. Clues to identification of new loci of gene loss in common adult solid tumours may be found in literature that describes chromosomal abnormalities in rare heritable cancers. Karyotypes of tumours in two families with hereditary renal carcinoma showed translocations involving the short arm of chromosome 3 (refs 10 and 11). We have examined tumours from 18 patients with non-hereditary renal cell carcinomas and found loss of alleles at loci on the short arm of chromosome 3 in all eleven of the patients who could be evaluated. PMID- 2885754 TI - Long-term potentiation of synaptic transmission in the hippocampus induced by a bee venom peptide. AB - Several neurotoxins have been isolated from bee venom. One of these, the mast cell degranulating peptide (MCD), releases histamine from mast cells and on central administration produces arousal at low concentrations and convulsions at higher doses. These effects are mediated through specific high-affinity binding sites which are concentrated in cortical structures, notably the hippocampus. This structure appears to be the source of changes in the electrocorticogram that follow injections of MCD into the cerebral ventricle, and which induce a quasi permanent hippocampal theta rhythm in the motionless rat alternating with epileptiform spike waves. We report here that brief application of MCD to the CA1 region of hippocampal slices induces long-term potentiation, that is, a long lasting increase in the efficacy of synaptic transmission. This potentiation seems to be indistinguishable from the classical LTP produced by trains of high frequency electrical stimulation and considered to be related in some way to memory. Using binding to synaptosomal membranes and radioimmunoassay techniques, we have also found an endogenous peptide equivalent of MCD in brain extracts. This raises the possibility that a MCD-like peptide may be important in long-term potentiation. PMID- 2885755 TI - Localization of the receptor-binding protein adhesin at the tip of the bacterial pilus. AB - Strains of the bacterium Escherichia coli that cause infections of the human urinary tract produce so-called Pap-pili, which are hair-like appendages consisting of about 10(3) helically arranged subunits of the protein PapA. These pili mediate binding to digalactoside-containing glycolipids present on the epithelial cells which line the urinary tract. Recently, it has been suggested that three proteins, PapE, PapF and PapG, are responsible for this binding. In the absence of PapA, non-piliated bacteria are formed which nonetheless exhibit binding, showing that the bulk of the pilus is not essential for binding. Although pili can form without PapF and PapG, such pili are unable to bind to the digalactoside. The protein PapG mediates binding specificity in trans complementation experiments, so this protein is the digalactoside-specific adhesin. Using immuno-electron microscopy we have found that Pap-pili are heteropolymers composed of the major pilin, PapA, the minor pilins, PapE and PapF, and the adhesin, PapG. The last three proteins are located at the tip of the pilus. PMID- 2885756 TI - Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. AB - Many hormones act on neuroendocrine cells by activating second messenger pathways. Two of these, the phosphoinositol and cAMP-dependent pathways, cause changes in cellular activity through specific protein kinases. By phosphorylating cytoplasmic and nuclear proteins, these kinases apparently coordinate cellular processes, including the biosynthesis and release of neuropeptides. Somatostatin biosynthesis and release, for example, are both positively regulated by the second messenger cAMP in hypothalamic cells, and cAMP also induces somatostatin gene transcription 8-10-fold in transfected PC12 pheochromocytoma cells. Transcriptional induction requires a 30-nucleotide cAMP response element (CRE) which is conserved in other cAMP-responsive genes. This element also confers cAMP responsiveness when placed upstream of the heterologous simian virus 40 (SV40) promoter. The somatostatin gene does not, however, respond to cAMP in mutant PC12 cells which lack cAMP-dependent protein kinase type II activity. Activation of somatostatin gene transcription may consequently require the phosphorylation of a nuclear protein which binds to the CRE. Using a DNase I protection assay, we have characterized a nuclear protein in PC12 cells which binds selectively to the CRE in the somatostatin gene. We have purified this protein which is of relative molecular mass 43,000 (Mr 43K) by sequence-specific DNA affinity chromatography. This 43K CRE binding protein (CREB) is phosphorylated in vitro when it is incubated with the catalytic subunit of cAMP-dependent protein kinase. Stimulating PC12 cells with forskolin, an activator of adenyl cyclase, causes a 3 4-fold increase in the phosphorylation of this protein. We conclude that the cAMP dependent pathway may regulate gene transcription in response to hormonal stimulation by phosphorylating this CREB protein. PMID- 2885757 TI - Regulation of T-cell receptor gamma-chain RNA expression in murine Thy-1+ dendritic epidermal cells. AB - The epidermis of normal mice contains two distinct populations of dendritic cells derived from the bone marrow, Ia+ Langerhans cells and Ia- cells that express the Thy-1 alloantigen. The Thy-1-bearing dendritic epidermal cells (Thy-1+ dEC) have a surface phenotype similar to that of very early T-lineage cells, produce IL-2 like growth factors and exhibit cytotoxicity which is not restricted by the major histocompatibility complex (MHC). The relationship of Thy-1+ dEC to the T-cell lineage is unclear. Most T lymphocytes bear a receptor for antigen composed of an alpha chain and a beta chain associated with a nonpolymorphic complex termed CD3 (T3). A minor population carries a receptor in which CD3 is associated with a gamma/delta complex. We have analysed clones of Thy-1+ dEC for rearrangement and expression of the genes for the alpha-, beta- and gamma-chains of the T-cell receptor (TCR). They do not express alpha or beta but do carry a gamma/delta complex. Activation of the cells with Con A is associated with a rapid decrease in the steady-state level of gamma-chain RNA. Because Thy-1+ dEC resemble early stage T lymphocytes, down-regulation of TCR expression may reflect a necessary event during T cell differentiation. PMID- 2885758 TI - Mapping the limits of the human pseudoautosomal region and a candidate sequence for the male-determining gene. AB - The human Y chromosome is composed of two different parts: a pseudoautosomal region shared with the X chromosome which is responsible for sex chromosome pairing and a Y-specific part that encodes the sex determining gene. Previously we have shown that the pseudoautosomal gene MIC2 only rarely recombines between the sex chromosomes and, based on the elevated recombination rates in the pseudoautosomal region, we predicted that this gene would lie close to the Y specific region. In this report we describe a test of this prediction using long range restriction mapping techniques. We conclude that MIC2 is less than 200 kilobases (kb) away from Y-specific sequences. During these experiments we have identified an HTF island in a position consistent with the proposed location of the human sex determining gene. PMID- 2885759 TI - Alpha 2-adrenoceptor-mediated responses to so-called selective alpha 1 adrenoceptor agonists after partial blockade of alpha 1-adrenoceptors. AB - In dog saphenous vein--a tissue possessing both postsynaptic alpha 1- and alpha 2 adrenoceptors--the effects of two selective alpha 1-adrenoceptor agonists (phenylephrine and methoxamine) were compared with that of the selective alpha 2 adrenoceptor agonist, UK-14,304, before and after phenoxybenzamine. Furthermore, the influence exerted by prazosin, yohimbine and verapamil on the effects of these agonists was also studied before and after phenoxybenzamine. In the absence of phenoxybenzamine, prazosin (56 nmol/l) caused a parallel shift of the concentration-response curves of both phenylephrine and methoxamine to the right (by 0.94 and 1.1 log units, respectively) and had no effect on the concentration response curve of UK-14,304, while 20 nmol/l yohimbine caused a marked parallel shift of the concentration-response curve of UK-14,304 to the right (by 1.18 log units) and caused only minor displacements of those of phenylephrine and methoxamine (by 0.2 and 0.33 log units, respectively). After exposure of the strips to 30 nmol/l phenoxybenzamine, prazosin (56 nmol/l) caused small shifts of the concentration-response curves of both phenylephrine (by 0.36 log units) and methoxamine (by 0.31 log units) and did not change that of UK-14,304, while yohimbine (20 nmol/l) caused pronounced parallel shifts of the concentration response curves (to the right) of all the agonists: phenylephrine (by 1.0 log units), methoxamine (by 0.93 log units) and UK-14,304 (by 1.28 log units).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885760 TI - Beta 2-adrenoceptor-mediated positive inotropic effect of adrenaline in human ventricular myocardium. Quantitative discrepancies with binding and adenylate cyclase stimulation. AB - Experiments were designed to unravel the relative contribution of beta 1- and beta 2-adrenoceptors to the positive inotropic effects of adrenaline and noradrenaline in isolated tissues of left ventricular myocardium of man. We also analyzed relationships between the fractions of human left ventricular beta 1- and beta 2-adrenoceptors, estimated from binding assays, and stimulation of adenylate cyclase and contractile force by adrenaline and noradrenaline. Selective blockade of beta 2-adrenoceptors by erythro-(+/-)-(alpha-methyl-indan-4 yloxy)-3-isopropylaminobuta n-2-ol (ICI 118,551) attenuated the increase of contractile force caused by adrenaline but not by noradrenaline, suggesting some involvement of beta 2-adrenoceptors. Selective blockade of beta 2-adrenoceptors without affecting beta 1-adrenoceptors still enabled both adrenaline and noradrenaline to cause maximum possible increases of contractile force through beta 1-adrenoceptors. A direct involvement of beta 2-adrenoceptors became manifest by selectively antagonizing beta 1-adrenoceptors by 1-[2[3-carbamoyl-4 hydroxy)phenoxy)ethylamino]- 3-[4(1-methyl-4-trifluoromethyl-2 imidazolyl)phenoxy]-2-propanol (CGP 20712 A) without affecting beta 2 adrenoceptor. beta 2-adrenoceptors can mediate half of the maximum increase of contractile force elicited by low concentrations of adrenaline and also contribute to the increase of contractile force caused by high concentrations of noradrenaline. beta-adrenoceptors were labelled in membrane particles with 3H-(-) bupranolol in the absence (beta 1 & beta 2) and presence of 500 nmol/l CGP 20712 A (beta 2). 71% of the beta-adrenoceptors were beta 1 and 29% beta 2. Binding inhibition experiments with CGP 20712 A and ICI 118,551 yielded 74% beta 1 and 26% beta 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885762 TI - [Salazosulfapyridine or 5-aminosalicylic acid]. PMID- 2885763 TI - [A young woman with Crohn's disease of the esophagus]. PMID- 2885761 TI - Inhibition of presynaptic alpha-2-adrenoceptor and opioid receptor agonist responses in the rat vas deferens by chronic imipramine treatment. AB - The effects of chronic imipramine administration on agonist responses in rat isolated smooth muscle preparations were investigated. The administration of 20 mg/kg imipramine two times a day for 4 and 11 days resulted in an equivalent subsensitivity (approximately 8-fold) of clonidine-induced inhibition of electrically evoked contractions in the rat vas deferens (presynaptic alpha 2 adrenoceptor response). Imipramine (4 days) resulted in a marked inhibition of the ability of [D-Ala2, D-Leu5] enkephalin to decrease electrically evoked contractions of the vas deferens (presynaptic opioid receptor response) but did not significantly affect the carbachol-induced increase in electrically evoked contractions (muscarinic receptor response). In the absence of cocaine the contractile effects of norepinephrine and tyramine in the vas deferens were, respectively, potentiated and inhibited, following imipramine (4 days), suggesting a decrease in the activity of the neuronal uptake mechanism. When determined in the presence of cocaine, the potency of the postsynaptic effects of norepinephrine in the vas deferens (alpha 1-adrenoceptor response) was not significantly altered by imipramine (4 days). With regard to other postsynaptic receptors, imipramine (4 days) decreased slightly the potency of phenylephrine in the aorta (alpha 1-adrenoceptor response) and increased slightly the potency of carbachol in the trachea (muscarinic receptor response) and the potency of serotonin in the rat aorta (5HT2-receptor response). Thus, chronic imipramine administration decreased the potency of presynaptic alpha 2- and opioid agonist responses in the vas deferens but caused very little or no changes in the potencies of agonists at postsynaptic sites. PMID- 2885764 TI - [Is this ameba dangerous?]. PMID- 2885765 TI - The excretion of urinary enzymes, proteins and creatinine in patients receiving cisplatinum. AB - The sensitive parameters of tubular nephrotoxicity during 4-day chemotherapy with new combination schedule of cisplatinum and 5-fluorouracil were followed. The determinations of tubular enzymes beta-glucuronidase (GRS) and gamma glutamyltransferase (GMT) in 24 hours urine, the excretion of creatinine and proteinuria were assayed before therapy and during 4 consecutive days of treatment. We recorded the significant increase of protein excretion and only slight increase of GMT and GRS activities after chemotherapy. The decrease of the creatinine excretion on the 3rd day of therapy was not statistically significant. Simultaneously followed serum creatinine and urea levels proved the elevation of creatinine only in 1 patient (the 1st grade according WHO classification). Our results suggest that the performed regime of chemotherapy produces only very low nephrotoxicity comparing to the 1-day administration of cisplatinum. These conclusions are confirmed also by the former examinations of GRS activities in cisplatinum therapy. PMID- 2885766 TI - [Dysarthrias in neurologic diseases]. AB - The clinical characteristics of dysarthria in neurological disease are reviewed in relation to the site of the lesion, giving special attention to dysarthria as an early symptom and to paroxysmal dysarthria. Iatrogenic and toxic causes of speech disorder are enumerated and the principles of diagnosis and therapy summarized. PMID- 2885767 TI - Tubular nephrotoxicity after intravenous urography with ionic high-osmolal and nonionic low-osmolal contrast media in patients with chronic renal insufficiency. AB - Nephrotoxicity of intravenous contrast media is more frequent and striking in patients with risk factors, the major one being preexisting chronic renal insufficiency. New nonionic low-osmolal contrast media allegedly have less nephrotoxicity than the traditional ionic high-osmolal ones. This was tested for two contrast media in a group of 18 patients with stable chronic renal insufficiency. The urinary excretion of two brush-border enzymes (alanine aminopeptidase, AAP, and gamma-glutamyl transpeptidase, gamma-GT) and of a lysosomal enzyme (N-acetyl-beta glucosaminidase, NAG), functional markers of tubular injury, were measured before and after intravenous urography with an ionic high-osmolal radiocontrast medium, meglumine sodium diatrizoate, or with a non ionic low-osmolal one, iopamidol. Urinary NAG excretion did not change significantly after administration of either contrast media. Urinary AAP and gamma-GT excretion increased significantly (p less than 0.01) after diatrizoate. After iopamidol, only gamma-GT excretion increased significantly (p less than 0.05). Our data suggest that the nonionic low-osmolal radiocontrast medium iopamidol is less toxic to tubules than the ionic high-osmolal medium diatrizoate and that the brush-border enzymes AAP and gamma-GT are sensitive markers for this toxicity. PMID- 2885768 TI - Sodium-dependent glutamate binding in senile dementia. AB - Sodium-dependent glutamate binding was studied as a possible index of the integrity of glutamate/aspartate (Glu/Asp) nerve endings in seven cortical areas from postmortem brains of 15 persons with senile dementia of the Alzheimer type (SD), 10 controls matched for age, sex and postmortem delay (PMD), and single cases of Down's syndrome and Parkinson-dementia. Binding affinities (Kd) were quite variable from brain to brain but showed no relation to sex, age, PMD or disease. Specific binding site densities did not vary with age or sex but showed overall a significant negative correlation with PMD, a significant decrease in SD, and a significant correlation in the SD--but not the control--samples with choline acetyltransferase (ChAT) activities. The binding data on individual brain regions, however, showed no significant difference between SD cases and controls despite highly significant differences in the ChAT activities. The overall results support but do not confirm a defect in cortical Glu/Asp systems in SD. Reported and obtained data on lesioned rats are summarized to suggest that sodium dependent glutamate binding may be an ineffective index of Glu/Asp nerve endings. PMID- 2885769 TI - Ethanol challenge alters amino acid neurotransmitter release from frontal cortex of the aged rat. AB - In two groups of male rats having an average age of either 90 days or two years, guide cannulae for bilateral push-pull perfusion were implanted stereotaxically to rest upon the superficial frontal cerebral cortex. On post-operative recovery, either 1.5 or 3.0 g/kg 20% ethanol (V/V) was given by intragastric gavage to each unrestrained rat. Sequential samples of venous blood were obtained from the tail and analyzed for alcohol levels by gas chromatography. A set of push-pull perfusions of the cortical sites was carried out with an artificial CSF before gavage and at 25, 50 and 150 min after the administration of ethanol. An individual perfusion was continued for 5.0 min at a rate of 25 microliters/min. Using high performance liquid chromatography with electrochemical detection (HPLC EC) each sample of perfusate was then assayed for its content of glutamate (Glu), aspartate (Asp), glutamine (Gln), glycine (Gly), taurine (Tau) and GABA with homoserine used as the internal standard. The results showed that the 3.0 g/kg dose of ethanol resulted in a higher level of blood ethanol in the older animals, which persisted over the 150 min time interval. Further, the 1.5 g/kg dose of ethanol administered to the older rats reduced the cortical activity of Glu and Gln relative to the younger animals. In addition, the 3.0 g/kg dose augmented the cortical efflux of Tau in the aged rats. Neither dose of ethanol affected the efflux of Asp or Gly from the perfused frontal cortex of either the young or old group, nor was the release of GABA detectable under either the control condition or following treatment with ethanol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885770 TI - Changes of cerebral gamma glutamyltransferase activities after treatment with exogenous inducers. AB - The activity of gamma-glutamyltransferase localized in isolated brain synaptic membranes- and microvessels-enriched fractions was assayed after treatment of rats with either phenobarbital or ethanol. Phenobarbital increased the activity of gamma-glutamyltransferase in microvessels, without alteration of synaptic membranes activity. An increase of enzyme activity was also obtained after a chronic intoxication with ethanol. These results suggest that the isoform of gamma-glutamyltransferase localized in brain microvessels may respond to exogenous inducers. PMID- 2885771 TI - Rapid eye movement sleep in man: modulation by benzodiazepines. AB - The modulation of rapid eye movement REM sleep in man by benzodiazepines has been analysed using 366 sleep recordings with at least 3 REM periods, obtained in 25 individuals, over 9 years. Sleep-dependent and sleep-independent mechanisms are believed to control REM activity, and the effect of benzodiazepines can be explained if the sleep-dependent influence is modified. It is suggested that a negative feedback mechanism, which usually encourages the appearance of REM periods, is depressed, while a threshold and oscillator which determine the cyclical appearance of the activity, and its relation with the onset of sleep, are unaffected. PMID- 2885772 TI - Evidence for control of cardiac vagal tone by benzodiazepine receptors. AB - Previous work has suggested that vagal preganglionic neurons which project to the heart, are tonically inhibited by endogenous gamma-aminobutyric acid (GABA). This study tested the hypothesis that benzodiazepines, which are thought to act by enhancing GABAergic inhibition, would increase heart rate by suppressing cardiac vagal activity in anesthetized rats, and that pretreatment with Ro 15-1788, a specific benzodiazepine receptor antagonist, would prevent tachycardia induced by benzodiazepines. Midazolam (0.05-4 mg/kg i.v.), alprazolam (1 mg/kg i.v.) and chlordiazepoxide (10 and 20 mg/kg i.v.), all evoked significant increases in heart rate. Pretreatment with atropine methobromide (2 mg/kg i.v.) increased the basal heart rate and prevented tachycardia induced by benzodiazepines. Basal heart rate and blood pressure were unchanged after pretreatment with Ro 15-1788 (10 mg/kg), but subsequent administration of any of the benzodiazepines failed to elicit increases in heart rate in these animals. These findings suggest that benzodiazepines may be potent vagolytics and that this effect should be considered before these agents are administered to patients who have suffered a recent myocardial infarction, in whom vagal tone is thought to be protective against fatal ventricular arrhythmias. PMID- 2885773 TI - Serotonin mediates cardiovascular responses to acetylcholine, bradykinin, angiotensin II and norepinephrine in the lateral septal area of the rat brain. AB - The infusion of acetylcholine, bradykinin, angiotensin II, norepinephrine and serotonin into the lateral septal area produced a dose-dependent increase of arterial blood pressure and heart rate. A pattern of inhibition of these cardiovascular responses, produced by pretreatment of the lateral septal area with phentolamine, 6-hydroxydopamine, methysergide and 5,7-dihydroxytryptamine was disclosed. These results suggest that the effects of acetylcholine, bradykinin and partially of angiotensin II, depend on the release of norepinephrine and the actions of this neurotransmitter in turn depend on the integrity of the serotonergic system in the lateral septal area. PMID- 2885774 TI - Cholecystokinin and bombesin in vagotomized or intact lean and obese rats: effects on neurotransmitters in brain. AB - Cholecystokinin (CCK) and Bombesin (BBS) are two neuropeptides which induce changes in monoamines in the brain after peripheral administration. A vagal mediation of these effects was investigated since the satiety responses to both peptides are affected differently by vagotomy. This work was performed on genetically obese and lean Zucker rats and on "cafeteria-fed" and lean Sprague Dawley rats as the effects of the peptides are dissimilar in these different groups. Vagotomy either inhibited or potentiated the peptide-induced effects, or created new variations. With CCK, the inhibition occurred mainly in the serotonergic system and in the Zucker strain, while new effects appeared in the dopaminergic system of lean rats of both strains. With bombesin, vagotomy inhibited the effects in the dopaminergic system in all lean rats, while new effects were observed in the serotonergic system in the Zucker strain. These data enable the differentiation of the mechanisms of action of both peptides and their selective effects, according to the strain of rat and the presence or absence of obesity. PMID- 2885775 TI - Nigrostriatal dopamine neurons: modulation of impulse-induced activation of tyrosine hydroxylation by dopamine autoreceptors. AB - The role of dopamine autoreceptors on nerve terminals in controlling the activity of tyrosine hydroxylase in the striatum was examined using a model involving supramaximal electrical stimulation of the nigro-neostriatal fibers and accumulation of 3,4-dihydroxyphenylalanine (DOPA) as a measure of the activity of tyrosine hydroxylase in vivo. In this way effects of drugs on impulse flow in these neurons could be negated and the effects on dopamine autoreceptors evaluated. Electrical stimulation, haloperidol, pimozide and clozapine increased the activity of tyrosine hydroxylase in vivo while trivastal, a dopamine agonist, had no significant effect. Combination of electrical stimulation with haloperidol or pimozide produced an additive effect on the activity of tyrosine hydroxylase, consistent with blockade of autoreceptors on nerve terminals. The combination of stimulation with clozapine (a drug shown to have minimal blocking action on autoreceptors in this model) produced an effect equivalent to stimulation alone, consistent with a lack of effect on autoreceptors. Trivastal reduced the effect of electrical stimulation, indicating a stimulatory action on dopamine autoreceptors on nerve terminals. These data are consistent with the theory of regulation of the activity of tyrosine hydroxylase in dopaminergic nerve terminals of the striatum by means of dopamine autoreceptors. PMID- 2885776 TI - Somatostatin, beta-endorphin, and prolactin levels in human cerebrospinal fluid during the gamma-vinyl-GABA treatment of patients with complex partial epilepsy. AB - The anticonvulsant action of the new anticonvulsant drug gamma-vinyl-GABA (GVG) is obviously mediated by elevation of the concentration of GABA in the brain. The effect of GVG administration on other transmitter systems is not fully known in humans. We studied the possible interactions of GVG administration with peptidergic systems. Included in this study were 67 patients with complex partial epilepsy (CPS). The first CSF sample was taken before GVG administration. The second CSF sample was taken after 3 months of GVG treatment (3 g/day). Thereafter half of the responders (50% decrease in seizure frequency or clear improvement in global performance) received 3 g/day and the other half received 1.5 g/day for the next three months, after which the third CSF sample was taken. Somatostatin (SLI), beta-endorphin (beta-EP), and prolactin (PROL) levels in CSF were measured by radioimmunoassay. Total GABA (tGABA) and GVG levels in CSF were measured by high performance liquid chromatography. After 3 months of GVG treatment there was a slight increase in the beta-EP (p = 0.027, Student's paired t-test), which was not found after 6 months of GVG administration. Both SLI and PROL were stable during the study. Peptide levels were not connected to the clinical response to GVG, GVG dosage, or to tGABA levels in the CSF. In conclusion, the elevation of GABA levels in the brain during GVG treatment apparently does not induce long term interactions with the peptidergic systems studied. PMID- 2885777 TI - Activation/inactivation of rat tissue pyroglutamate aminopeptidase by disulfide bond-reducing agents. AB - The effects of dithiothreitol on pyroglutamate aminopeptidase activity in rat serum, spinal cord, brain, liver, kidney, and adrenal extracts were investigated in vitro. Addition of dithiothreitol to the reaction mixture resulted in noncompetitive inhibition of serum (Ki = 2.1 +/- 0.3 mM) and brain (Ki = 3.2 +/- 0.28 mM) enzymes and stimulation of liver, spinal cord, kidney and adrenal enzymes with an increase in Vmax but not Km. The findings of these studies suggest that the properties of Pyroglutamate aminopeptidases vary from tissue to tissue. PMID- 2885779 TI - A re-examination of the localization of immunoreactive dynorphin(1-8), [Leu]enkephalin and [Met]enkephalin in the rat neurohypophysis. AB - We addressed in this study, with immunocytochemical methods, the following questions: are immunoreactive enkephalins in the rat neurohypophysis stored in nerves distinct from neurosecretory nerves; where is [Met]enkephalin immunoreaction localized; does immunoreactive [Leu]enkephalin coexist with pro enkephalin or with pro-dynorphin fragments; and are the interpretations of localization studies influenced by the choice of pre-embedding or post-embedding immunocytochemical techniques? We compared immunoreactions due to antibodies which had been used by others in previous studies, examined both lyophilized and conventionally fixed specimens, and applied pre- and post-embedding protocols. Both pre- and post-embedding stainings confirmed co-storage of immunoreactive dynorphin(1-8)-like materials with vasopressin. Immunoreactive [Met]enkephalin like material always coexisted with oxytocin. Most of the immunoreactive [Leu]enkephalin-like material appeared to occur in oxytocin nerves; only in larger vasopressin varicosities was there some dot-like [Leu]enkephalin immunoreaction. This indicates that neural lobe [Leu]enkephalin predominantly is cleaved from a precursor which also contains [Met]enkephalin. When pre-embedding methods were modified in order to block diffusion and to enhance penetration of antibodies, enkephalin immunoreactivity was always found in typical neurosecretory varicosities with large granules. Structures previously interpreted as enkephalinergic nerve terminals contacting pituicytes most likely are neurosecretory varicosities. PMID- 2885778 TI - Immunocytochemical demonstration of the presence of catecholamine and serotonin neurons in the sheep olfactory bulb. AB - The catecholamine and serotonin innervation of the sheep olfactory bulb was studied using immunocytochemistry. Specific antisera raised against tyrosine hydroxylase, dopamine beta-hydroxylase, phenylethanolamine N-methyl transferase and serotonin were used. Tyrosine hydroxylase-positive cell bodies were present in all cell layers except in the anterior olfactory nucleus, the greatest number being found in the glomerular layer. Neither dopamine beta-hydroxylase-positive nor serotonin-positive cell bodies were observed. Dopamine beta-hydroxylase positive fibers were widely distributed in the granule cell layer but less widely in other layers. The glomerular layer contained the greatest distribution of serotonergic positive fibers, but such fibers were also visualized in other cell layers. No phenylethanolamine N-methyl transferase-positive structures were found in this investigation. PMID- 2885780 TI - Neuropeptide Y, somatostatin, and reduced nicotinamide adenine dinucleotide phosphate diaphorase in the human striatum: a combined immunocytochemical and enzyme histochemical study. AB - Neuropeptide Y and somatostatin immunoreactive neurons and processes were examined in human striatum using both immunofluorescence and avidin biotin immunoperoxidase methods. Reduced nicotinamide adenine dinucleotide phosphate diaphorase activity was histochemically determined by the reduction of nitro blue tetrazolium. Immunofluorescence using a monoclonal anti-somatostatin antibody and a polyclonal anti-neuropeptide Y antibody, followed by diaphorase histochemistry, showed that these three neurochemical markers are co-localized in a single population of medium-sized aspiny intrinsic neurons. Cells were evenly distributed in clusters throughout the striatum, but fiber density was higher in the nucleus accumbens and ventromedial regions of the caudate and putamen. Double stained reduced nicotinamide adenine dinucleotide phosphate diaphorase acetylcholinesterase sections demonstrated that these neurons are located in zones of high acetylcholinesterase activity, often at the interface of these zones with regions of low enzyme activity. These biochemically distinctive neurons are uniquely situated to modulate activity between striatal compartments. Our findings provide new information about the modular organization of the striatum and extend these observations in human brain. PMID- 2885781 TI - Lophotoxin: selective blockade of nicotinic transmission in autonomic ganglia by a coral neurotoxin. AB - Lophotoxin is a diterpene lactone isolated from gorgonian corals. The toxin has previously been shown to bind with high affinity to an acetylcholine recognition site located on skeletal muscle nicotinic receptors, producing an essentially irreversible blockade of neuromuscular transmission. Lophotoxin has also been shown to block nicotinic transmission in autonomic ganglia of the frog and in ileal strips of guinea pig and rabbit. The effects of lophotoxin have now been examined on neuronal nicotinic receptors in autonomic ganglia of the chick and rat. Low concentrations of lophotoxin (1 microM) produce a blockade of neuronal nicotinic transmission which is partially reversed by 3-5 h of washing out the toxin. The blockade produced by higher concentrations of lophotoxin (up to 32 microM) is not reversed during a similar washout period. Prior exposure to d tubocurarine, a competitive nicotinic antagonist, can partially protect ganglia against exposure to lophotoxin. In contrast the local anesthetic QX-314, a noncompetitive nicotinic antagonist, does not protect ganglia against lophotoxin exposure. Lophotoxin binds to a site in ganglia identified by [125I]kappa bungarotoxin which appears to be on the neuronal nicotinic receptor. Intracellular recordings reveal that lophotoxin has no effect on either muscarinic responses or on responses to gamma-aminobutyrate in autonomic ganglia. Passive and active membrane properties of the neurons are unaffected by lophotoxin except for the blockade of nicotinic responses. It is concluded that lophotoxin is a selective, high-affinity antagonist at the neuronal nicotinic receptor. The long-term nature of the blockade with lophotoxin suggests that the toxin will be of considerable value as a probe for characterizing the ganglionic nicotinic receptor. PMID- 2885782 TI - Division of small intensely fluorescent cells in neonatal rat superior cervical ganglion is inhibited by glucocorticoids. AB - Postnatal genesis of small, intensely fluorescent cells was studied in the rat superior cervical ganglion by combining immunocytochemistry of tyrosine hydroxylase with tritiated thymidine autoradiography. After injection of tritiated thymidine during the first postnatal week, silver grains were observed over the nuclei of many small cells with intense staining for tyrosine hydroxylase, suggesting that SIF cells are dividing postnatally. Cell counts in ganglia of rats sacrificed 2 h after tritiated thymidine showed that the rate of SIF cell proliferation was highest during the first postnatal week with approximately 20% of SIF cells dividing and that the rate declined thereafter. Counts of labeled SIF cells at 30 days in rats injected with tritiated thymidine on days 0, 2, 4, 6, 8, 10 or 14 revealed a peak of SIF cell birthdays on day 8. In these long-survival experiments, many labeled SIF cells were present in adult superior cervical ganglions. In contrast, only one labeled principal neuron was observed in a total of 450 sections. Glucocorticoid treatment of the rats during the first postnatal week paradoxically increased the number of SIF cells, but inhibited the rate of SIF cell proliferation. Dividing SIF cells immunoreactive for both tyrosine hydroxylase and phenylethanolamine N-methyltransferase were observed in glucocorticoid-treated rats. These observations suggest that many SIF cells are dividing during the first postnatal week. After cessation of division, these cells either remain SIF cells or die, but do not differentiate into principal neurons. Since glucocorticoids do not stimulate SIF cell proliferation, they must increase the number of SIF cells by biasing the differentiation of precursor cells in the superior cervical ganglion and/or enhancing SIF cell survival. PMID- 2885784 TI - Essential tremor: a review. PMID- 2885783 TI - Monozygotic female twin carriers discordant for the clinical manifestations of Duchenne muscular dystrophy. AB - We studied twin sisters, in their sixth decade, who were obligate carriers of Duchenne dystrophy. One had a slowly progressing limb-girdle myopathy since her mid-20s. The other sister showed no evidence of neuromuscular disease by history or on physical examination but had high serum CK values and degeneration and regeneration of fibers in a muscle biopsy. Otherwise, they were phenotypically identical, karyotypically normal females with cytogenetically normal X chromosomes. Based on red cell and HLA loci antigen determinations, there was a 99.2% probability that they were monozygotic. The mutant gene segregating in the family is probably linked to the Xp21 DNA marker pERT87. PMID- 2885785 TI - [Angiitis caused by hypersensitivity or microscopic polyarteritis nodosa. Recent findings. I. Nosographic aspects]. AB - Hypersensitivity angiitis or microscopic polyarteritis nodosa is one of the necrotising angiitis and was not distinguished from classic polyarteritis nodosa until the Fifties. The present study examines the nosographic aspects of necrotising angiitides with reference to the anatomohistological, aetiopathogenic and clinical criteria proposed by various Authors for their identification and with emphasis on the fact that all these factors must be borne in mind for the purpose of diagnosis. The factors that make it possible to distinguish hypersensitivity angiitis from other necrotising angiitides are, at clinical level, the presence of skin lesions, and in anatomohistological terms the involvement of the small blood vessels and leucocytoclasia. PMID- 2885786 TI - [Treatment of duodenal ulcer with rosaprostol in patients resistant to treatment with anti-H2]. AB - The results obtained with the combined treatment Rosaprostol + anti-H2 in 10 patients with duodenal ulcer previously treated with insufficient results with anti-H2 drugs are described (in comparison with other 10 patients under the same conditions treated with anti-H2 alone). The results are clearly favourable (statistical significance) for Rosaprostol. The drug was well tolerated. PMID- 2885787 TI - [Hypersensitivity angiitis or microscopic polyarteritis nodosa. Recent findings. II. Clinical aspects]. AB - Hypersensitivity angiitis is one of the commonest necrotising vasculitides. Given the ubiquitous distribution of the small blood vessels almost any part of the body may be affected. However benign forms predominantly involving the skin are the most common. Forms predominantly involving the viscera and that may prove fatal are rare. Among the polymorphous skin lesions encountered "palpable purpura" is the most common and its palpability is a vital element in differential diagnosis. Among non-cutaneous sites the kidneys are the most frequent and glomerular involvement is the commonest cause of death. Though laboratory tests provide no specific data they may indicate the severity of visceral involvement. PMID- 2885788 TI - [Possibilities and limitations of the therapy of headache]. PMID- 2885789 TI - [Chronic headache]. PMID- 2885790 TI - [Ulcerative rectocolitis and pregnancy]. PMID- 2885792 TI - Chronic morphine treatment reduces the incidence of ventricular arrhythmias in the isolated rat heart induced by dynorphin1-13 or myocardial ischemia and reperfusion. AB - We have studied the effects of a daily morphine injection for 2 weeks on induction of naloxone-reversible arrhythmias in the Langendorff isolated rat heart preparation caused by dynorphin1-13 or myocardial ischemia and reperfusion. Chronic morphine treatment significantly reduced the incidence and severity of arrhythmias and increased recovery following both administration of dynorphin and myocardial ischemia and reperfusion. The results support the notion that myocardial ischemia and reperfusion induce cardiac arrhythmias via endogenous opioid peptides. PMID- 2885791 TI - Renal micropolyarteritis: a treatable condition. AB - A 10-year retrospective study of 36 patients is presented; the patients comprised 27 with renal micropolyarteritis nodosa (microPAN) and nine with Wegener's granulomatosis. At presentation, 29 patients had significant renal impairment (creatinine greater than 150 mumol/l), with 18 requiring dialysis at some time during their illness. Eighteen patients showed rapid recovery of renal function, a further two with apparently chronic renal failure recovered renal function after 4 months dialysis and continued immunosuppression. Seven patients required chronic dialysis. No benefit was shown for any particular immunosuppressive regime, with three patients recovering renal function (two initially on dialysis) without any immunosuppression. Prognosis was better than in previous published series, especially considering the elderly population (mean 52.9 years), with an 80% 1-year and a 64% 5-year survival. PMID- 2885793 TI - Regulation of the release of neuronally localized corticosterone in rat forebrain areas by catecholamines. AB - The influence of intralimbic and intrahypothalamic application of catecholamine related compounds on the release of neuronally localized corticosterone in the central amygdala, ventral hippocampus and medial hypothalamus was investigated under in vivo and in vitro conditions. It is reported that agonists and antagonists of the alpha-adrenergic system did not affect the release of corticosterone in the brain areas studied. In contrast, the beta-adrenoreceptor agonist isoprenaline markedly enhanced the release of corticosterone. This response is prevented in the presence of the beta-adrenoreceptor antagonist propranolol. The data reveal that limbic and hypothalamic beta-adrenoreceptors play a role in the regulation of corticosterone release and suggest a functional interaction between catecholaminergic and corticosterone releasing neurons in forebrain areas. PMID- 2885794 TI - Visualization of tyrosine hydroxylase-immunoreactive neurons in the cat dorsal motor vagal cells after treatment with parachlorophenylalanine. AB - We examined tyrosine hydroxylase-immunoreactive (TH-IR) neuronal structures in the cat dorsal motor nucleus of the vagus (DMV) and its adjacent regions. We identified only a few in the caudal part of the DMV and no TH-IR cells at all in its rostral portion. However, after treatment with parachlorophenylalanine (PCPA), numerous TH-IR perikarya were visualized in the DMV. Comments are made on the central catecholamine regulation and the possible influence of serotonin afferents on this nucleus. PMID- 2885795 TI - Joro spider venom: glutamate agonist and antagonist on the rod retina of the dogfish. AB - The venom of the Joro spider, reported to block glutamate action selectively at some glutaminergic synapses, was applied focally to rod horizontal and on-bipolar cells in dark-adapted retinal slices. The venom hyperpolarized horizontal cells in the dark and blocked their responses to light. Depolarization of horizontal cells by ionophoretic pulses of L-glutamate, L-aspartate or kainate was antagonized by the toxin in a slowly reversible manner. These results are consistent with other evidence for glutamate as the rod neurotransmitter acting on a single postsynaptic receptor type on horizontal cells. In contrast, the venom, like glutamate, closed the same ion channels of on-bipolar cells as the transmitter, thereby blocking light responses of on-bipolars. Joro spider toxin distinguishes the glutamate receptor-channel complexes of rod horizontal and on bipolar cells. PMID- 2885796 TI - Acute effects of methamphetamine applied microiontophoretically to nucleus accumbens neurons in rats. AB - Microiontophoretic studies were performed to elucidate the acute effects of methamphetamine on the nucleus accumbens (Acc) neurons receiving input from the parafascicular nucleus (Pf) of the thalamus using rats anesthetized with chloral hydrate. Spike generation upon Pf stimulation was inhibited by conditioning stimuli applied to the ventral tegmental area (VTA), which is rich in dopamine containing neurons, and by iontophoretic application of methamphetamine as well as dopamine. The VTA-, methamphetamine- and dopamine-induced inhibition of the spikes elicited by Pf stimulation was antagonized during simultaneous application of haloperidol. Glutamate-induced firing was also inhibited during iontophoretic application of methamphetamine and dopamine in neurons receiving input from the Pf, and the inhibition was blocked by simultaneously applied haloperidol. In the reserpine-treated animals, however, the Pf-induced spikes were not affected by methamphetamine, but inhibited by dopamine. These results indicate that methamphetamine inhibits the Acc neurons receiving input from the Pf, probably by releasing dopamine from dopaminergic nerve terminals from the VTA. PMID- 2885797 TI - Dystrophic symptoms prevented by phenobarbital in avian muscular dystrophy. AB - New Hampshire normal (line 412) and dystrophic (line 413) chickens were treated with central stimulants and central depressants, respectively, once a day from the 2nd to the 10th day after hatching, and effects of the treatment were examined on a number of muscle fibers, areas of muscle fibers, and the coefficient of variation of a muscle on the 13th day. Central depressants, especially phenobarbital, effectively prevented development of the dystrophic symptoms, whereas central stimulants made normal chickens "dystrophic". The righting ability of the dystrophic chickens was normal after treatment with 10 mg/kg of phenobarbital during the early postnatal period from the 2nd to the 28th day after hatching. PMID- 2885798 TI - [Anesthetics--prescription abuse--results of a study]. PMID- 2885799 TI - Localization of gamma-glutamyl transpeptidase in the epithelial transitional zones. PMID- 2885800 TI - Neuropharmacology of the injured spinal cord. PMID- 2885801 TI - Small and large intestinal guanylate cyclase activity in children: effect of age and stimulation by Escherichia coli heat-stable enterotoxin. AB - Heat-stable enterotoxin (ST) producing Escherichia coli are a common cause of diarrhea in infants. ST acts through the stimulation of the guanylate cyclase cGMP system. The effect of ST on the human intestine has not been investigated nor is any information available on the activity, distribution, or development of guanylate cyclase activity in the human intestine. The purpose of this study, therefore, was to characterize, these aspects of guanylate cyclase activity and to study the effect of ST on the activity and responsiveness of guanylate cyclase in the intestine of infants and children of various ages. We measured guanylate cyclase activity in 35 intestinal specimens, obtained operatively, from children aged 1 day to 16 yr. Guanylate cyclase activity was linear with protein concentration and time. Basal activity was similar in small intestine and in colon. In the small intestine, however, basal guanylate cyclase activity varied with age. It was maximal in children 1 day of age, and although somewhat variable, decreased with age thereafter. In colon, an age-related pattern was not found. E. coli ST stimulated guanylate cyclase activity in all specimens in a dose-related manner. In the small intestine ST-stimulation of guanylate cyclase was twice that found in colon. Furthermore, age affected the response of small intestinal guanylate cyclase to ST. Maximal response to ST was observed in children 1 day of age and ST stimulation was significantly greater in children less than 1 yr of age than in older children. In the colon, the response of guanylate cyclase to ST did not change with age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885802 TI - Erythromycin in the treatment of pertussis: a study of bacteriologic and clinical effects. AB - In an open randomized study 17 patients with a positive culture for Bordetella pertussis were treated for 10 days with erythromycin (50 mg/kg/day divided in 2 doses). The bacterium could not be isolated during therapy and in only one patient was it isolated 5 days after cessation of treatment. In comparison B. pertussis was isolated 10 and 15 days after diagnosis from 10 and 4 patients, respectively, of a group of 21 untreated controls. The treated group developed significantly fewer whoops than did the control group, even though most of the individuals had reached the paroxysmal stage at diagnosis. The dose of erythromycin (ethylsuccinate and stearate preparations) gave serum concentrations about 100 times larger than the minimal inhibitory concentration of isolated bacteria and was well-tolerated. Thus adequate erythromycin treatment eliminates B. pertussis from the nasopharynx and reduces symptoms in patients having a history of pertussis of less than 14 days. Adequate dosage and length of treatment might be crucial for these results. PMID- 2885803 TI - [Treatment of bronchial asthma in children]. PMID- 2885806 TI - Polypurine/polypyrimidine sequence elements of the murine homeo box loci, Hox-1, 2 and -3. PMID- 2885804 TI - A study of the post-tetanic twitch depression at the prostatic end of the rat vas deferens. AB - The effects of different drugs on the post-tetanic twitch responses of the prostatic end of the isolation rat vas deferens were examined. Following repetitive field stimulation (4-5 Hz for 40-60 s), the post-tetanic twitches (0.2 0.5 Hz) were depressed relative to the steady-state pretetanic twitches. Maximum post-tetanic twitch depression (PTD) occurred 15-30 s after the tetanic stimulation. The PTD was not reversed but deepened and prolonged by the presynaptic alpha 2-adrenoceptor antagonists idazoxan (RX781094) or yohimbine (10(-7) M) alone or combined with the neuronal uptake blocker, desipramine (10( 6) M). The PTD was insensitive to the beta-adrenoceptor blocker, propranolol (10( 6) M), the P1-purinoceptor antagonist, 8-phenyltheophylline (10(-5) M) or the prostaglandin E synthesis inhibitor, indomethacin (10(-6) M). Pre- and post tetanic contractions to superfused noradrenaline (NA), adenosine 5'-triphosphate (ATP), or beta, gamma-methylene ATP (beta, gamma-mATP) (bolus injections into superfusate, 1-8 X 10(-5) M) were not significantly (p less than 0.01) different. The PTD was absent in high magnesium (6.2-11.2 mM) solutions. These results are consistent with the PTD having an intrinsic presynaptic origin. They are discussed in relation to stimulation-induced modulation of transmitter release. PMID- 2885807 TI - A HindIII polymorphism in the 3' end of the human alpha 1(IV) collagen gene. PMID- 2885808 TI - A polymorphic locus, D10S5, at 10q21.1. PMID- 2885805 TI - Human mRNA polyadenylate binding protein: evolutionary conservation of a nucleic acid binding motif. AB - We have isolated a full length cDNA (cDNA) coding for the human poly(A) binding protein. The cDNA derived 73 kd basic translation product has the same Mr, isoelectric point and peptidic map as the poly(A) binding protein. DNA sequence analysis reveals a 70,244 dalton protein. The N terminal part, highly homologous to the yeast poly(A) binding protein, is sufficient for poly(A) binding activity. This domain consists of a four-fold repeated unit of approximately 80 amino acids present in other nucleic acid binding proteins. In the C terminal part there is, as in the yeast protein, a sequence of approximately 150 amino acids, rich in proline, alanine and glutamine which together account for 48% of the residues. A 2,9 kb mRNA corresponding to this cDNA has been detected in several vertebrate cell types and in Drosophila melanogaster at every developmental stage including oogenesis. PMID- 2885809 TI - Anonymous DNA sequence from chromosome 21 showing a three allele insertion/deletion RFLP (HGM 9 provisional no. D21S82). PMID- 2885810 TI - PstI RFLP identified by an anonymous single copy genomic clone localized to chromosome 14 (HGM 9 provisional no. D14S14). PMID- 2885811 TI - A novel form of human polymorphism involving the hDHFR-psi 1 pseudogene identifies three RFLPs. PMID- 2885812 TI - EcoRI RFLP at the creatine kinase-brain type gene locus (CKBB, chromosome 14). PMID- 2885813 TI - A Taq I polymorphism for the human transforming growth factor alpha gene (TGFA). PMID- 2885815 TI - [Qualitative and quantitative changes in APUD cells in celiac diseases in children and adults]. PMID- 2885814 TI - [Use of hemoperfusion in the treatment of acute poisoning with the preparation Reladorm]. PMID- 2885817 TI - [Neuroendocrinologic regulation of the immune system function]. PMID- 2885816 TI - [Kidney changes in viral hepatitis in the light of enzymatic analysis of the urine]. PMID- 2885818 TI - Pain in the foot. 1. Evaluation of foot pain and identification of associated problems. PMID- 2885819 TI - Ultrasound imaging of the scrotum. A pictorial guide to its varied capabilities. PMID- 2885820 TI - Pharmacologic therapy for bronchial asthma. AB - Many drugs with which to treat reversible obstructive airway disease are available. Beta-adrenergic aerosols are the first line of defense; these are followed, when necessary, by either timed-release theophylline or oral beta adrenergics. Often, a combination of these drugs must be used to achieve effective relief of symptoms. Once-daily theophylline preparations can be extremely effective in patients who need regular medication and in whom gastrointestinal upset or compliance is a problem. In patients who have frequent setbacks, occasional courses of tapered doses of steroid are necessary. When oral steroids are necessary regularly, the physician should consider using an aerosol corticosteroid, cromolyn sodium, or both. These drugs can be used daily with relative safety. However, only a small amount (ie, no more than 12%) of an inhaled medication reaches the lungs. In selected patients, regular doses of cromolyn sodium are used for prophylaxis and may preclude the need for theophylline or oral beta-adrenergics, which can have deleterious effects in adults and children. Cromolyn sodium is most effective if used before exercise or exposure to animals. Research is continuing on more effective and longer-acting beta-adrenergic aerosols and oral preparations. PMID- 2885821 TI - [Beta-2 specificity of bronchially active sympathomimetics using capillary laser Doppler sonography exemplified by tulobuterol]. PMID- 2885822 TI - [Clostridium perfringens enterotoxemia. Fatal form in a 5-year-old child]. PMID- 2885823 TI - [Is calcium a primum movens in the pathogenesis of cerebrovascular accidents?]. AB - Concerning the physiological cascade associated with cerebral vascular accidents, numerous studies have been devoted to a search for a key element (outside the initial fall in blood perfusion) responsible for the noxious jumble that leads to tissue necrosis. As a fundamental element of cell physiology, calcium intervenes in a number of vital functions, but when present in excessive amounts it may engender disorders by accelerating reactions which it normally regulates. Thus, in cerebral tissue, and notably in acute ischaemia, calcium is held responsible for additional phenomena of coagulation, exacerbated neurotransmitter discharge or even cell poisoning by paralysis of mitochondrial respiration. Based on these data, attempts have been made to treat cerebral vascular accidents by the so called calcium antagonists. Experimentally or clinically, the results obtained, although divergent, show that acting on calcium movements contributes to total or partial correction of the complex physiopathology of cerebral ischaemia. A new generation of calcium antagonists is needed to oppose the fundamental disorders engendered, notably those of mitochondrial function. PMID- 2885824 TI - [Effects of aging and various pharmacologic agents on the brain energy metabolism in the course of post-hypoglycemic recuperation in the rat]. AB - Severe acute hypoglycaemia with isoelectric electroencephalogram induces a major deterioration of the energy state and amino acid contents of the brain. During post-hypoglycaemia recovery of adult animals, brain glucose concentrations return to normal values, whereas glycogen turnover remains low as aspartate and pyruvate concentrations increase. ATP levels rise, but the adenine-nucleotide pool remains small despite return to normal of ADP and AMP. Brain phosphocreatine levels return to normal values, with reciprocal changes in creatine content. In adult rats one also notes during recovery an increase in brain glutamine and glutamate, whereas the gamma-aminobutyrate returns to normal. Finally, ammonium and aspartate remain below, and alanine remains above normal values. Aging has no effect on cerebral metabolic disturbances induced by hypoglycaemia, but it influences the cerebral metabolic restoration processes that develop during post hypoglycaemia recovery. The restitution of cerebral metabolites is weaker in mature and senescent rats than in adult rats. In the oldest rats, in particular, the concentrations of most of the amino acids and of adenyl nucleotides remain largely abnormal. The effects of dihydroergocristine, erbunamonine, raubasine, almitrine and of the almitrine-raubasine combination on post-hypoglycaemia recovery were evaluated in adult, mature and senescent rats. During recovery these pharmacological agents exert different effects on glycolytic metabolites, amino acids and energy-rich phosphates. PMID- 2885825 TI - [Metabolic and blood circulation evaluation of acute ischemic cerebral accident in humans using positron emission tomography]. AB - Positron emission tomography and oxygen-15 were used to evaluate the effects of an almitrine-raubasine combination on cerebral blood flow and oxydation metabolism in patients with acute cerebral ischaemia. In 5 patients, aged between 58 and 74 years, with cerebral ischaemic accident in the territory of the middle cerebral artery, blood flow rate, oxygen consumption and brain oxygen extraction were measured before and after a 90-min intravenous infusion of almitrine bismesilate 15 mg and raubasine 5 mg. Only one patient presented with initial relative luxury perfusion, the intensity of which was reduced by the combined treatment. The other 4 patients had focal reduction of cerebral blood flow and oxygen consumption prior to treatment. Statistical analysis conducted on three cerebral areas (epicentre of the lesion, anterior and posterior juxtalesional areas and homologous heterolateral areas) showed a significant 3.6% increase of oxygen consumption in the epicentre, both hemispheres included, and a significant increase of cerebral blood flow in all three areas (3% on the healthy side, 13% on the diseased side). No significant change in oxygen extraction was demonstrated. The authors conclude that acute almitrine-raubasine treatment has beneficial effects on the brain immediately after a cerebral vascular accident, reflecting respect of the circulation-metabolism couple. PMID- 2885826 TI - [Quantified electroencephalogram: value in the evaluation of therapy of cerebral aging]. AB - Computerized quantification of electroencephalograms enables pharmacological compounds designed to counteract pathological cerebral aging to be evaluated. The results obtained by this method when substances which sedate or stimulate the central nervous system are used suggest the existence of a negative correlation between neuronal activity and electroencephalographic power. More precisely, the application of this method to pharmacology suggests a relation with the activity of one or several neurotransmission systems. By extension, studies of cerebral aging may benefit from this new technique of cerebral exploration because it allows the demonstration of age related changes in the EEG effect of drugs studied in physiological conditions. Thus we have demonstrated an interaction between the almitrine-raubasine combination and the noradrenergic system in rats. In clinical pharmacology, the evaluation of these two compounds is still liable to numerous experimental biases. The almitrine-raubasine combination was tested in controlled trials in elderly people complaining of intellectual deterioration; the results obtained were fairly similar to those observed in old rats, thus demonstrating an effect on the central nervous system and perhaps also an action on the noradrenergic system in human. PMID- 2885827 TI - [Psychometric evaluation of the effects of an almitrine-raubasine combination in the intellectual deterioration of aged subjects. A double-blind controlled trial versus placebo]. AB - The clinical and psychometric evaluation of a drug to be used against the intellectual deterioration associated with cerebral aging is of obvious interest when carried out on ambulatory subjects, since the symptoms likely to be reduced are found in elderly people usually living at home. Thirty-six patients (18 male, 18 female; mean age 65.5 +/- 1.7 years) were selected and allocated at random to two treatment groups. They received during 2 months 80 drops per day in two doses of either an almitrine-raubasine combination or a placebo. Patients definitely entered the trial when Hachinski's score for ischaemia was equal or inferior to 7. They were evaluated at zero, 1 and 2 months by means of 3 performance tests (Toulouse-Pieron test, Tapping test, numbers memorization test) and 2 mood tests (Hamilton's scale, Zung's questionnaire). All mean scores of recognition tests were statistically improved in the almitrine-raubasine group after 2 months of treatment. Compared with the placebo group, the improvement in the almitrine raubasine group was significant at 1 month for 3 medium scores (symbols omitted, taping, numbers in normal order) and for all scores at 2 months. The psycho behavioural symptoms evaluated by the two mood scores were significantly improved in the almitrine-raubasine group (P less than 0.001) and in comparison to the placebo group after 1 and 2 months (P less than 0.001). These results concerning intellectual performance and mood demonstrate that the almitrine-raubasine combination is useful in the treatment of intellectual deterioration in elderly people living at home. PMID- 2885828 TI - [Serum monoclonal immunoglobulins and HIV-I infection]. PMID- 2885829 TI - [The syndrome of tissue resistance to thyroid hormones]. AB - Known since 1967 and usually familial, the syndrome of tissue resistance to thyroid hormones may take one of two different forms, depending on the receptors involved. When resistance affects both peripheral and pituitary receptors, plasma thyroid hormone levels are high despite the lack of thyrotoxicosis, thyroxine and triiodothyronine are ineffective, even in high dosage, and plasma TSH increases to explode under TRH. When resistance only affects pituitary receptors, there is moderate thyrotoxicosis with paradoxical and inappropriate TSH increase. Contrary to expectations, nuclear receptors to triiodothyronine are perturbed in only a few cases. Reduction of thyrotropic hyperfunction, which is the primary purpose of treatment, can be achieved with D-forms of thyroid hormones or with somatostatin and its derivatives. PMID- 2885830 TI - [Duodenal fistula. Treatment with small doses of somatostatin]. PMID- 2885831 TI - [A new case of the Sipple syndrome]. PMID- 2885832 TI - Drug treatment of obsessive-compulsive disorder: a review of findings in the light of diagnostic and metric limitations. AB - Nearly every category of psychotropic drug has been investigated in an attempt to find a pharmacologic treatment for obsessive compulsive disorder (OCD). This study reviews published trials from the English literature in which tricyclic antidepressants, monoamine oxidase inhibitors, neuroleptics, benzodiazepines, and other agents were employed for treatment of OCD. Weaknesses in the current methodology including diagnosis, measurement of severity and criteria for improvement have contributed to invalid conclusions about drug treatment and efficacy. It appears that OCD is an etiologically heterogeneous disorder with a complex differential diagnosis. For the clinician, a major conclusion drawn from this review is that no agent emerges as a drug of choice. Although clorimipramine, the most actively investigated agent, shows some promise, it has not been conclusively demonstrated that other, more readily available heterocyclic agents are less effective. Furthermore, when other disorders co exist, such as panic disorder, alternative agents may prove as effective. PMID- 2885833 TI - Strategies of clinical research on neurobiological determinants of psychosis. AB - Despite great efforts in clinical psychiatric research in the last decades, many simple questions still remain open. Present day clinical practice still lacks theoretically founded and generally accepted therapeutic rules, especially in the individual case. Similarly, in basic research we are far from understanding the etiopathogenetics of psychiatric illness. From summarizing some aspects of previous research strategies and results in neurobiological determinants in psychosis, future research strategies are outlined, which already have proven successful and thus should be pursued more rigorously. Not least because of general limited research capacities with respect to time and costs, future research has to proceed economically, i.e. guided by clear strategies. PMID- 2885834 TI - Molecular cloning and sequence of a cDNA coding for bovine lipoprotein lipase. AB - Lipoprotein lipase (LPL; triacylglycero-protein acylhydrolase, EC 3.1.1.34) was purified from bovine milk. Synthetic oligonucleotides were prepared, based on the amino acid sequences of three peptides obtained from partial digestion of purified LPL, and were used as probes to isolate cDNA clones for LPL mRNA from a bovine mammary gland. One of the clones, pLPL-49R2, contains an insert cDNA (49R2) of about 3.2 kilobases (kb) that hybridizes to all three probes and encodes a polypeptide that includes the NH2-terminal sequence of bovine LPL reported recently [Ben-Avram, C. M., Ben-Zeev, O., Lee, T. D., Hagga, K., Shively, J. E., Goers, J., Pedersen, M. E., Reeve, J. R. & Schotz, M. C. (1986) Proc. Natl. Acad. Sci. USA 83, 4185-4189]. Complete nucleotide sequence analysis revealed that cDNA insert 49R2 contains the entire coding region for LPL as well as a 3' untranslated region of about 1.6 kb. The predicted amino acid sequence indicates that bovine LPL is a hydrophilic protein consisting of 450 amino acids (Mr 50,548) in its unglycosylated form. Blot hybridization analysis of poly(A)+ mRNA from bovine mammary gland demonstrated that there are at least three sizes of LPL mRNAs--3.2, 2.5, and 1.7 kb--with the 2.5-kb mRNA being the most abundant. Restriction endonuclease mapping of other cDNA clones suggested that the variation in mRNA size results from differential utilization of polyadenylylation signals during mRNA processing. PMID- 2885835 TI - Characterization of the promoter region of the human c-erbB-2 protooncogene. AB - Three overlapping genomic clones that contain the 5'-terminal portion of the human c-erbB-2 gene (ERBB2) were isolated. The promoter region was identified by nuclease S1 mapping with c-erbB-2 mRNA. Seven transcriptional start sites were identified. DNA sequence analysis showed that the promoter region contains a "TATA box" and a "CAAT box" about 30 and 80 base pairs (bp), respectively, upstream of the most downstream RNA initiation site. Two putative binding sites for transcription factor Sp1 were identified about 50 and 110 bp upstream of the CAAT box, and six GGA repeats were found between the CAAT box and the TATA box. This region had strong promoter activity when placed upstream of the bacterial chloramphenicol acetyltransferase gene and transfected into monkey CV-1 cells. These data indicate that the promoter of the human c-erbB-2 protooncogene is different from that of the protooncogene c-erbB-1 (epidermal growth factor receptor gene), which does not contain either a TATA box or a CAAT box. Comparison of the promoter sequences and activities of the two protooncogenes should be helpful in analysis of the regulatory mechanism of expression of their gene products, which are growth-factor receptors. PMID- 2885837 TI - Pst I restriction fragment length polymorphism of the human placental alkaline phosphatase gene in normal placentae and tumors. AB - The structure of the human placental alkaline phosphatase gene from normal term placentae was studied by restriction enzyme digestion and Southern blot analysis using a cDNA probe to the gene for the placental enzyme. The DNA digests fall into three distinct patterns based on the presence and intensity of an extra 1.1 kilobase Pst I band. The extra 1.1-kilobase band is present in 9 of 27 placenta samples, and in 1 of these samples the extra band is present at double intensity. No polymorphism was revealed by digestion with restriction enzymes EcoRI, Sma I, BamHI, or Sac I. The extra Pst I-digestion site may lie in a noncoding region of the gene because no correlation was observed between the restriction fragment length polymorphism and the common placental alkaline phosphatase alleles identified by starch gel electrophoresis. In addition, because placental alkaline phosphatase is frequently re-expressed in neoplasms, we examined tissue from ovarian, testicular, and endometrial tumors and from BeWo choriocarcinoma cells in culture. The Pst I-DNA digestion patterns from these cells and tissues were identical to those seen in the normal ovary and term placentae. The consistent reproducible digestion patterns seen in DNA from normal and tumor tissue indicate that a major gene rearrangement is not the basis for the ectopic expression of placental alkaline phosphatase in neoplasia. PMID- 2885836 TI - Identification of residues required for ligand binding to the beta-adrenergic receptor. AB - The functional significance of conserved polar amino acids within the putative transmembrane region of the beta-adrenergic receptor (beta AR) was examined by oligonucleotide-directed mutagenesis of the hamster gene encoding beta AR and expression of the mutant genes in COS-7 cells. Although a substitution of aspartate at position 113 with an asparagine residue did not affect expression or processing of the protein, the resulting mutant beta AR did not show detectable binding toward the antagonist iodocyanopindolol. Replacement of the aspartate and asparagine residues at positions 79 and 318, respectively, had no effect on the affinity of the receptor toward antagonists but reduced the affinity of the receptor toward agonists by 1 order of magnitude. Furthermore, we observed that substitution of the proline at position 323 with a serine residue resulted in improper or incomplete processing of the beta AR, presumably reflecting a role for this residue in the folding of the receptor. Together with our previous results from deletion mutagenesis studies, these observations indicate that the ligand binding site involves the transmembrane region of the beta AR. PMID- 2885838 TI - Alpha-chain locus of the T-cell antigen receptor is involved in the t(10;14) chromosome translocation of T-cell acute lymphocytic leukemia. AB - Human leukemic T cells carrying a t(10;14)(q24;q11) chromosome translocation were fused with mouse leukemic T cells, and the hybrids were examined for genetic markers of human chromosomes 10 and 14. Hybrids containing the human 10q+ chromosome had the human genes for terminal deoxynucleotidyltransferase that has been mapped at 10q23-q25 and for C alpha [the constant region of TCRA (the alpha chain locus of the T-cell antigen receptor gene)], but not for V alpha (the variable region of TCRA). Hybrids containing the human 14q- chromosome retained the V alpha genes. Thus the 14q11 breakpoint in the t(10;14) chromosome translocation directly involves TCRA, splitting the locus in a region between the V alpha and the C alpha genes. These results suggest that the translocation of the C alpha locus to a putative cellular protooncogene located proximal to the breakpoint at 10q24, for which we propose the name TCL3, results in its deregulation, leading to T-cell leukemia. Since hybrids with the 10q+ chromosome also retained the human terminal deoxynucleotidyltransferase gene, it is further concluded that the terminal deoxynucleotidyltransferase locus is proximal to the TCL3 gene, at band 10q23-q24. PMID- 2885839 TI - Thy-1+ dendritic epidermal cells express T3 antigen and the T-cell receptor gamma chain. AB - The murine epidermis is a heterogeneous epithelium composed of keratinocytes, melanocytes, Langerhans cells, and a recently described subpopulation (2-3%) of bone-marrow-derived leukocytes with a dendritic morphology and the cell surface phenotype Thy-1+, L3T4-, Lyt-2-. Previous studies have demonstrated that cell lines derived from freshly explanted Thy-1+ dendritic epidermal cells (DEC) have abundant mRNA for rearranged T-cell receptor (TCR) gamma-chain genes. Analysis of Thy-1+ DEC in situ, freshly isolated cell suspensions of Thy-1+ DEC, and long term Thy-1+ DEC lines demonstrated that 100% of the Thy-1+ DEC reacted with a monoclonal antibody to the epsilon chain of the murine T3 complex and that 40-60% of resident Thy-1+ DEC were also reactive with an antiserum to the TCR gamma chain. Two Thy-1+ DEC lines expressed a disulfide-linked 70-kDa molecule that could be precipitated with an anti-gamma-chain antiserum and could be coprecipitated with an antiserum to the T3 delta chain; the molecule appeared as a single 34-kDa band under reducing conditions. The phenotype of Thy-1+ DEC (T3+, L3T4-, Lyt-2-, TCR gamma chain+) thus resembles that of the recently described subpopulation of murine and human lymphocytes that have been identified in the thymus, peripheral blood, and fetal blood. PMID- 2885840 TI - HLA-DR2 subtypes form an additional supertypic family of DR beta alleles. AB - Homozygous lymphoblastoid cell lines representing Dw subtypes of the DR2 serotype were studied for structural polymorphism at DR beta. These subtypes included Dw2, Dw12, and non-Dw2/non-Dw12. Analysis by two-dimensional gel electrophoresis showed that two DR beta genes were expressed in each cell line studied. One of these expressed genes encoded a protein that was nonpolymorphic on two dimensional gel electrophoresis among all subtypes. The second expressed DR beta gene was polymorphic and migrated to a position on two-dimensional gels dependent on the subtype of the cell line. cDNA sequence analysis of the DR beta genes revealed a DR beta gene identical between the Dw2 and Dw12 subtypes, which correlates with the nonpolymorphic spot on two-dimensional gels. A second gene was sequenced that exhibited variability between the Dw2 and Dw12 subtypes. This variability takes the form of clustered point mutations in the first domain of the molecules. The alleles from the DR beta genes of a non-Dw2/non-Dw12 cell line, AZH, were unusual in sequence. In contrast to other DR beta alleles, the AZH genes may have been generated by a double recombinational event between two DR beta loci from a DR2 parent. The DR2 serotype may also constitute a supertypic "family," with one DR beta gene relatively nonpolymorphic, and one that varies with Dw subtype. PMID- 2885841 TI - Identification of HLA-DP polymorphism with DP alpha and DP beta probes and monoclonal antibodies: correlation with primed lymphocyte typing. AB - Thirty-four lymphoblastoid cell lines that had been previously typed for HLA-DP antigens by primed lymphocyte typing (PLT) were tested by Southern blotting and by ELISA. Using two DP beta probes and a DP alpha probe with a series of enzymes, it is possible to identify restriction fragment length polymorphism (RFLP) patterns characteristic of DPw1, -2, -3, -4, and possibly -5. ELISA typing results, based on two polymorphic DP antibodies DP11.1 and ILR1, were compared with PLT-defined and RFLP-defined types. Thus, using a range of probes and enzymes it is possible to identify DP polymorphism. The value of monoclonal antibodies for such studies is demonstrated, and the molecular data can, in some cases, pinpoint the amino acids responsible for the specificity of the monoclonal antibodies. PMID- 2885842 TI - Hepatitis B virus produced by transfected Hep G2 cells causes hepatitis in chimpanzees. AB - We have reported that clonal cells derived from Hep G2 cells transfected with a plasmid containing hepatitis B virus (HBV) DNA secrete spherical and filamentous forms of hepatitis B surface antigen (HBsAg), core particles, and virions into the culture medium. Here we describe the development of typical hepatitis in two chimpanzees following intravenous inoculation with the medium in which the transfected cells had grown. The liver biopsies from these animals showed characteristic lesions in parenchyma and portal tracts, more conspicuous at an earlier time in the chimpanzee that had received a greater number of virions. The amount of HBsAg in the serum of one infected chimpanzee increased with time after the initial inoculation and then decreased concomitantly with the appearance of antibodies against HBsAg and core antigens. HBsAg remained detectable in the other animal throughout the course of the experiment. The levels of hepatitis B "e" antigen in both animals peaked at week 5, signifying the acute phase of the infection. The activities of serum enzymes that are markers for necroinflammation also increased. The hepatitis HBsAg subtype of the virions isolated from the patient whose DNA was cloned and then used for transfection of the Hep G2 cells was the same as that found in the chimpanzees. Furthermore, the restriction enzyme analysis of the viral DNA isolated from the chimpanzees was identical to the cloned DNA. Thus, HBV DNA-transfected Hep G2 cells can support the replication of virions that, in turn, produce hepatitis in chimpanzees. PMID- 2885844 TI - Two human homeobox genes, c1 and c8: structure analysis and expression in embryonic development. AB - Two human cDNA clones (HHO.c1.95 and HHO.c8.5111) containing a homeobox region have been characterized, and the respective genomic regions have been partially analyzed. Expression of the corresponding genes, termed c1 and c8, was evaluated in different organs and body parts during human embryonic/fetal development. HHO.c1.95 apparently encodes a 217-amino acid protein containing a class I homeodomain that shares 60 out of 61 amino acid residues with the Antennapedia homeodomain of Drosophila melanogaster. HHO.c8.5111 encodes a 153-amino acid protein containing a homeodomain identical to that of the frog AC1 gene. Clones HHO.c1 and HHO.c8 detect by blot-hydridization one and two specific polyadenylylated transcripts, respectively. These are differentially expressed in spinal cord, backbone rudiments, limb buds (or limbs), heart, and skin of human embryos and early fetuses in the 5- to 9-week postfertilization period, thus suggesting that the c1 and c8 genes play a key role in a variety of developmental processes. Together, the results of the embryonic/fetal expression of c1 and c8 and those of two previously analyzed genes (c10 and c13) indicate a coherent pattern of expression of these genes in early human ontogeny. PMID- 2885843 TI - Aberrant transmembrane signal transduction in Dictyostelium cells expressing a mutated ras gene. AB - Dictyostelium discoideum cells contain a single ras gene (Dd-ras) that is highly homologous to mammalian ras genes. Cell transformation with a vector carrying a ras gene with a (glycine----threonine) missense mutation at position 12 causes an altered morphogenesis. Extracellular cAMP signals regulate morphogenesis and induce chemotaxis and the activation and subsequent desensitization of adenylate and guanylate cyclase. cAMP signal transduction was investigated in Dd-ras transformed cells. Transformants that overexpress the mutated Dd-ras-Thr12 gene show normal activation and desensitization of adenylate cyclase and normal activation of guanylate cyclase. However, cAMP induces a stronger desensitization of guanylate cyclase stimulation in the Dd-ras-Thr12 transformant than in transformants overexpressing the Dd-ras-Gly12 wild-type gene or in untransformed cells. This effect was correlated with a reduced chemotactic sensitivity of the transformant expressing the mutated Dd-ras-Thr12 gene. PMID- 2885845 TI - Parathyroid hormone-related protein purified from a human lung cancer cell line. AB - A protein with biological activities similar to parathyroid hormone (PTH) has been purified from serum-free culture medium obtained from a human lung cancer cell line (BEN). A major protein band of 18 kDa was obtained on NaDodSO4/polyacrylamide gels, with faint bands at 35 kDa and 67 kDa. Biological activity was associated only with the 18-kDa band. Amino acid sequence analysis of the material purified by HPLC revealed that 8 of the 16 residues were identical with those of human PTH. Antibody raised to a corresponding synthetic peptide recognized the PTH-related material but showed less than 1% cross reactivity with human PTH amino-terminal peptides. BEN cells contained PTH DNA, but not PTH messenger RNA, indicating involvement of another gene. The purified PTH-related protein had a specific biological activity approximately equal to 6 times greater than that of bovine PTH(1-34). The PTH-related protein may have a role in the syndrome of humoral hypercalcemia of malignancy. PMID- 2885846 TI - Interleukin 1 regulates hematopoietic activity, a role previously ascribed to hemopoietin 1. AB - A murine in vitro assay was developed to measure potentiation of a proliferative response to suboptimal concentrations of the hematopoietic regulatory molecule granulocyte/macrophage colony-stimulating factor by an immature bone marrow population. The assay, designated the 5-fluorouracil bone marrow proliferation assay, was used to characterize potentiating activity in serum-free culture supernatants of the human tumor cell line HBT 5637. Molecular and biochemical analyses indicated that the HBT 5637-derived potentiating activity could be attributed to interleukin 1 alpha. Serologic analysis using a monoclonal antibody against purified recombinant interleukin 1 alpha proved conclusively that the potentiating activity in HBT 5637 serum-free supernatants is due to interleukin 1 alpha. From these data, the activity of interleukin 1 alpha seems to be the same synergistic activity formerly ascribed to hemopoietin 1. PMID- 2885847 TI - Primary structure and nuclear localization of a murine homeodomain protein. AB - The murine homeobox Hox 1.1 (m6) is the first of a cluster of six boxes on chromosome 6. Using probes and synthetic peptides derived from the Hox 1.1 sequence, we were able to isolate cDNAs and antibodies that allowed us to characterize the product of this homeobox-containing gene. From the open reading frame on the cDNA clone B21, a protein could be predicted, made up of 229 amino acids and having a calculated molecular weight of 25,740. A unique feature of this protein is that it has 15 glutamic acid residues as its carboxyl terminus, which gives it a very hydrophilic and acidic carboxyl terminal structure, most probably folding onto an alpha-helix. A second domain of six amino acids is present on the Hox 1.1 protein, which is conserved in other homeodomain proteins. Antibodies generated against synthetic peptides from the homeobox region were used in the immunoblotting procedure and revealed a major protein band of Mr 31,000 in extracts from 3T3 cells and F9 teratocarcinoma cells induced by retinoic acid and cAMP. The nuclear location of the protein was established by immunofluorescence. The presence of this protein in F9 cell nuclei is in faithful accordance with the kinetics established for the 2.4-kilobase Hox 1.1 transcript during differentiation into parietal endoderm cells. PMID- 2885849 TI - The Wellcome Foundation lecture, 1986. The molecular control of normal and leukaemic granulocytes and macrophages. AB - The development of semisolid culture methods supporting the clonal proliferation and maturation of granulocytes and macrophages led to the discovery of a group of specific glycoproteins, the colony-stimulating factors (CSFs), whose function it is to control the proliferation and functional activity of granulocytes, macrophages and associated blood cells. The four known CSFs in the mouse and man have been purified and complementary DNAs (cDNAs) for each have been cloned. The injection of bacterially synthesized recombinant CSF into mice has demonstrated that these CSFs can function in vivo to regulate granulocyte and macrophage formation. A major physiological role played by these CSFs is to control resistance to invading microorganisms through mechanisms capable of extremely rapid activation. Because the CSFs are the only known proliferative factors for these cells, the CSFs are involved in the initiation and the emergence of myeloid leukaemia but, conversely, at least one of the CSFs, G-CSF, is able to suppress myeloid leukaemic populations because of the ability of the CSFs to initiate differentiation commitment in responding granulocytic and macrophage populations. The CSFs are promising agents for clinical use in the treatment of infections in patients with depressed granulocyte-macrophage formation and possibly in the management of some types of myeloid leukaemia. PMID- 2885848 TI - Genes encoding alpha and beta subunits of Na,K-ATPase are located on three different chromosomes in the mouse. AB - We have made use of a panel of mouse-hamster somatic cell hybrids and restriction fragment length polymorphisms between two mouse species (Mus musculus and Mus spretus) to determine the chromosomal localization of genes encoding the alpha and beta subunits of the Na,K-ATPase (Na+,K+-activated ATP phosphohydrolase, EC 3.6.1.3). DNA probes for three distinct isoforms of the Na,K-ATPase alpha subunit mapped to three different mouse chromosomes: the alpha 1 gene (Atpa-1) cosegregated with the Egf gene on chromosome 3; alpha 2 (Atpa-2) with the cytochrome P-450PB gene family/coumarin hydroxylase locus on chromosome 7; alpha 3 (Atpa-3) with the alpha-spectrin gene on chromosome 1. The Na,K-ATPase beta subunit gene (Atpb) mapped to the same region of chromosome 1, but it was not tightly linked to the Atpa-3 gene. These results indicate that three isoforms of the Na,K-ATPase alpha subunit are encoded by three distinct genes. The dispersion of Na,K-ATPase genes suggests that their expression is not likely to be controlled by a common cis-acting regulatory element. PMID- 2885850 TI - In vitro formation of neuromuscular junctions between adult Rana muscle fibres and embryonic Xenopus neurons. AB - Adult muscle fibres of the frog Rana temporaria were cultured with neurons from embryos of the frog Xenopus laevis. Electron microscopical and electro physiological examination of the cultures showed that hetero-specific (Xenopus Rana) neuromuscular junctions were formed in vitro. Nerve processes, without any Schwann cell covering, made contacts anywhere along a muscle fibre, and the junctions resembled those seen during early regeneration of neuromuscular synapses in situ. Functional contacts, as inferred by the presence of spontaneous miniature endplate potentials, or currents, were more common if the muscle fibres were denervated prior to culturing with neurons. Miniature endplate currents (m.e.p.cs) had a skewed amplitude distribution, with many small events lost in the recording noise, and their mean amplitude was much smaller than that of m.e.p.cs in the original lumbricalis muscle. The time constant of decay of m.e.p.cs in the hetero-specific junctions formed in vitro was several times longer than the decay of m.e.p.cs in the original muscle. Analysis of membrane current noise elicited by ionophoretically applied acetylcholine (ACh) suggests that the slower decay of m.e.p.cs in the junctions formed in vitro is due to a prolonged lifetime of the channels opened by ACh and to repetitive activation of ACh-receptors, which becomes possible because of a comparative lack of cholinesterase in the junctions. PMID- 2885851 TI - Periarteritis nodosa in rats treated with chronic excess sodium chloride (NaCl) after X-irradiation. AB - Five-week-old male Crj:CD (SD) rats were treated with excess sodium chloride after abdominal X-irradiation. The gastric regions of the rats were irradiated with a total dose of 20 Gy given in two equal fractions separated by 3 days. After X-irradiation, animals were fed a diet containing 10% sodium chloride. Red blood cell anemia appeared 22 weeks after the last irradiation. By gross observation, the mesenteric arteries became reddish in color, and bead- or lead pipe-like nodular thickenings were present. Microscopically, these nodularly thickened mesenteric arteries showed fibrinoid necrosis with massive inflammatory infiltration including eosinophils and neutrophils. In more advanced lesions, elastica interna and externa and medial smooth muscle cells disappeared completely and were replaced by granulation tissue. In old lesions, arterial walls were markedly thickened with fibrous or fibromuscular tissue. These findings were quite similar to those of the human periarteritis nodosa. These arterial lesions could not be found in the rats with X-irradiation only, sodium chloride only, or in nontreated animals. This study demonstrates X-ray-induced, NaCl-promoted periarteritis nodosa-like lesions in rats. PMID- 2885852 TI - Cloning of a putative chicken MHC class II alpha chain gene. PMID- 2885854 TI - Double-blind comparison of astemizole and terfenadine in the treatment of chronic urticaria. AB - Two new non-sedating antihistamines, astemizole (10 mg per day) and terfenadine (120 mg per day), were compared in a double-blind randomized study in 42 adult patients suffering from chronic urticaria. The trial lasted 4 weeks. Patients were evaluated at 2 and 4 weeks and kept a daily diary of their symptoms. There was a statistically significant decrease in pruritus, erythema and urticaria papules in both groups throughout the study. Changes in papule size, number and frequency were greater in the astemizole group though not significantly different to the terfenadine group. The effect of astemizole increased with time whereas that of terfenadine decreased after about 3 weeks of treatment. Astemizole was globally considered to be the most effective drug by both investigator and patients, with excellent/good results in 77% of the patients compared with 55% to 60% in the terfenadine group. Both drugs were reported to be more effective and faster acting than other antihistamines taken previously. Side-effects were infrequent and minor in both groups. PMID- 2885853 TI - Astemizole suspension in the maintenance treatment of paediatric hay fever: a comparison with terfenadine suspension. AB - A study was carried out in general practice during the summer months of 1985 to compare the efficacy and tolerance of astemizole suspension with terfenadine suspension in the treatment of paediatric hay fever. The 65 patients who entered the study were all aged between 6 and 12 years and had suffered from hay fever in at least one previous season. Each child was randomly allocated to receive either 5 ml astemizole suspension (1 mg/ml) once daily or 5 ml terfenadine suspension (6 mg/ml) twice daily for a period of 8 weeks on a single-blind basis. Symptom scores assessed by the patient (or parent/guardian) on two visual analogue scales for ocular and nasal symptoms showed no significant difference between the treatment groups, neither did an analysis of visual analogue scores for runny nose, blocked nose, wheeze, sneezing or eye symptoms assessed by the investigator on entry or after 4 and 8 weeks. The global assessments made by the investigator at 4 weeks and the patient at 8 weeks, however, indicated significantly better overall symptom control in the astemizole group. Both treatments were well tolerated, side-effects being few and minor. PMID- 2885855 TI - Effects of centrally administered H2 antagonists on motor activity. AB - Two structurally distinct H2 antagonists, cimetidine and BMY 25,368, were injected into the cerebral ventricles of mice. Both drugs produced reductions in locomotor activity and rotorod latencies. The effects of the H2 antagonists on locomotor activity were attenuated by the H2 agonist, impromidine, as well as by the H1 antagonist, chlorpheniramine. When given alone, chlorpheniramine had no effect on locomotor activity, while impromidine reduced locomotion. These data suggest that histaminergic receptors may mediate important actions on arousal and sedation mechanisms. PMID- 2885856 TI - Harman induces preference for ethanol in rats: is the effect specific for ethanol? AB - Increasing concentrations of either ethanol, etonitazene, clomethiazole or midazolam were offered to male Wistar rats for 21 days. Between day 8 and day 21, the animals were treated with several doses of harman, harmalan, and tetrahydronorharman (tetrahydro-beta-carboline) by means of continuous intraventricular infusion. Harman and THN induced a significant preference for ethanol in a dose-dependent manner. Harman was approximately three times more potent than THN. The amount of ethanol consumed during the second and third weeks of the experimental period correlated with the harman concentration in the brain after the cessation of the treatment (p less than 0.01). Harman infusion attenuated the clomethiazole intake, whereas that of etonitazene and midazolam was not affected as compared with CSF-treated rats. By counting licking movements, it was found that the rats drank ethanol and water at distinct time periods with the pattern dependent on the concentration of the ethanol solution offered. The intervals between the maxima were 6 to 8 hours at low ethanol concentrations. Relatively high concentrations caused a disruption of the regular rhythms in favour of shorter ones with increasing intervals between the maxima (3 hr, 4 hr, 5 hr intervals). Harman treatment (27 nmol/hr) disturbed the regular rhythms at lower ethanol concentrations but mimicked the ultradian rhythm which was observed at high ethanol concentrations in CSF-treated animals. The observed coincidence of water and ethanol intake was uncoupled if the highest ethanol concentration in both treatments was offered. Thus, treatment with harman changed the rhythm of fluid intake in a direction which was detected in CSF-treated rats only at relatively high ethanol concentrations. PMID- 2885857 TI - Effects of dapiprazole on contractile responses of guinea pig isolated ileum. AB - The effects of dapiprazole, a relatively new alpha 1-adrenolytic agent, on contractile responses and on spontaneous mechanical activity were studied in guinea pig isolated ileum. Dapiprazole (10(-10) to 10(-4) M) produced a concentration-dependent inhibition of high K+ (80 mM) -induced contractions. These inhibitory effects were observed with dapiprazole added either before or after the induced contractions. The Ca2+-induced contractions of K+-depolarized ileum were also inhibited by dapiprazole. Dapiprazole inhibited in a non competitive manner the responses of the ileum to: carbachol, histamine, 5 hydroxytryptamine, pentagastrin, angiotensin II and cholecystokinin. In order to analize whether dapiprazole exerts an intracellular effect on Ca2+-store, skinned preparations were used. The results suggest that dapiprazole might inhibit Ca2+ entry through both voltage-and receptor-operated channels of the smooth muscle membrane. PMID- 2885858 TI - Acute hepatic damage in rats impairs metharbital metabolism. AB - Metharbital metabolism was impaired in rats after acute hepatic damage induced by carbon tetrachloride. Compared to control rats, hepatic damage prolonged the metharbital sleeping time and reduced the slopes of log metharbital plasma concentration-time curves. Renal contributions to metharbital elimination from plasma were negligible since only about 6% of the metharbital administered was eliminated unchanged in urine. In rats with hepatic damage, metharbital clearance from plasma and elimination of its demethylated metabolite, barbital, in urine decreased with increasing severity of damage. These results indicate that the kinetics of both metharbital and its metabolite reflect sensitively hepatic drug metabolizing capacity. Measuring urinary elimination of barbital, following metharbital administration, may serve as a convenient laboratory test to evaluate the hepatic drug-metabolizing capacity. PMID- 2885859 TI - Differential inhibitory effects of nicorandil, a new antiangina agent, on the contractile responses to alpha-1- and alpha-2-adrenoceptor agonists in isolated rabbit renal and femoral arteries. AB - In the renal and femoral artery, nicorandil (10(-6)-10(-4) mol/l) had a much greater inhibitory effect on the responses to clonidine (CL) and BHT-920 than on the response to methoxamine (MO) but the inhibitory action of nifedipine on the responses was no different. In the presence of nifedipine, nicorandil further inhibited the responses to all agonists. In the tissue pretreated with phenoxybenzamine, nicorandil inhibited the residual maximum response to MO in the femoral artery but not in the renal artery. Nicorandil had no effect on the residual response to high concentrations of MO in the renal artery pretreated with phenoxybenzamine and nifedipine. Relationship between maximum contraction and percent-receptor occupancy was found to be nonlinear for MO but was close to linear for CL. The inhibitory effect (pA2) of prazosin on MO and CL was much greater than that of yohimbine. In both preparations, nicorandil had only a slight inhibitory effect on the responses to potassium and Ca2+. It is concluded that the responses induced by MO, CL and BHT are due to activation of alpha 1 adrenoceptors and that the differential effect of nicorandil on the responses to alpha 1- and alpha 2-agonists may be the result of differences in the amount of receptor reserves and/or efficacy of receptor-contraction coupling that exists for MO, CL and BHT. PMID- 2885860 TI - Lipophilic beta-adrenoceptor antagonists stimulate low density lipoprotein receptor activity in human skin fibroblasts. AB - The effect of beta-adrenoceptor antagonists on the receptor-mediated low density lipoprotein (LDL) binding and internalization was studied in vitro in human skin fibroblasts. The cellular uptake of 125I-labeled human LDL was dose dependently elevated by some, but not all, of the drugs used. This effect of beta adrenoceptor antagonists was positively related to their lipophilicity, and was prevented by cycloheximide and by alpha-amanitin. Scatchard analysis of the saturable LDL binding indicates an increased number of LDL binding sites. Our studies show that the stimulating effect of beta-adrenoceptor antagonists on the high affinity LDL binding and internalization in human skin fibroblasts involves DNA transcription and new protein synthesis, and identify drug lipophilicity as a major determinant of this action. This effect could be relevant in vivo in adipose tissue which accumulates lipophilic drugs and derives its cholesterol mainly from circulating LDL. PMID- 2885861 TI - Innervation of airway smooth muscle. Efferent mechanisms. AB - The classical view, with one excitatory (cholinergic) and one inhibitory (noradrenergic) component, of the innervation of airway smooth muscle is incomplete and at least two other, possibly peptidergic, types of innervation must be included when the innervation of airways is considered. A summary of these neuronal components is given in Fig. 1 and their possible origin is outlined. Besides the inhibitory noradrenergic innervation of the airways observed in some species, an inhibitory NANC (i-NANC) innervation has been demonstrated. The polypeptide, VIP, seems to be the most likely candidate for the neurotransmitter in the i-NANC innervation of the airways. The excitatory cholinergic innervation is present in the airways from the trachea down to the peripheral bronchi. In the guinea-pig bronchi an excitatory NANC (e-NANC) innervation has been demonstrated as well. The e-NANC nerves may correspond to chemosensitive primary afferent nerves with substance P or a related tachykinin as transmitter. When the innervation of airway smooth muscle of different mammalian species is compared it is evident that all nerve components except the cholinergic, show a considerable variability among species. The cholinergic innervation seems to be present in all mammalian species whereas the other components may be completely absent from some species. Distinct regional variations in the innervation of the airways may occur, which is exemplified by the distribution of the autonomic innervation in the guinea-pig tracheo-bronchial tree. Cholinergic neurotransmission in for example the guinea-pig and human airways can be modulated by NA via prejunctional inhibitory alpha 2 adrenoceptors. Furthermore, the e-NANC neurotransmission in the guinea-pig airways may be modulated by NA or by selective alpha 2-adrenoceptor agonists, acting via prejunctional inhibitory alpha 2-adrenoceptors. The clinical importance of the NANC innervation in relation to asthma is discussed. The i-NANC nerves may exert a modulating effect on bronchoconstriction, and a functional defect would presumably lead to an exaggerated response to constrictor stimuli. The e-NANC nerves in the airways may also be clinically relevant since the transmitter (tachykinins) from these nerves can produce bronchoconstriction and promote inflammation of the airway epithelium, either by direct mechanisms or indirectly by activation of mast cells, and thus contribute to the features of asthma.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2885863 TI - Plasma biogenic amine levels in agoraphobia with panic attacks. AB - Eight patients with agoraphobia and panic attacks as defined by DSMIII and 11 controls were included in this study which measured the circulating biogenic amine levels. The method of assay used a high performance liquid chromatograph with electrochemical detection. Measurement of dopamine, noradrenaline and adrenaline showed no differences between the groups. Levels of serotonin (5-HT) were significantly lower in the agoraphobic group. The authors discuss the implication of this finding. PMID- 2885862 TI - Neuropharmacology of drugs affecting food intake. AB - The importance of the central monoamines NE, DA and 5-HT in ingestive behavior has inevitably resulted in considerable effort being expended in attempting to implicate these monoamines in the mechanism of action of anorectic drugs. The statements that amphetamine-induced anorexia is unlikely to be due to central serotoninergic systems and that central noradrenergic and dopaminergic systems are not implicated in the appetite suppressant effect of fenfluramine are in all probability correct. However, to attribute the ability of drugs to decrease food intake unequivocally to a specific effect on central monoaminergic systems is almost certainly an oversimplification, due to the fact that other putative neurotransmitters, such as GABA and peptides, play a critical role in eating. This can be achieved either directly or by modulating the release of other transmitters. An added complication in attempting to correlate a specific neurochemical process to a behavioral effect, such as anorexia, is the complexity of the central actions of the drug. At best, a predominant but not an exclusive process can be identified. Perhaps the in-built constraint of attempting to correlate a specific neurochemical effect to the desired action of a drug is accountable for the absence of a second generation of centrally acting anorectic drugs. Dramatic progress has been made in elucidating the factors involved in ingestive behavior over the last 5-10 years. This information should, and must, provide the catalyst for more efficacious anorectic drugs because obesity represents one of the few major diseases for which adequate drug therapy does not exist. PMID- 2885864 TI - Autonomic nervous system differences as predictors of short-term outcome in schizophrenics. AB - Skin conductance and heart rate of 19 drug-free acute schizophrenic patients were measured before neuroleptic therapy was started. The patients were divided into two groups according to therapeutic outcome. The Discriminant Analysis revealed a difference in the ANS activity pattern between the group with low improvement and the group with a more favorable outcome. The low improvement group showed a paradoxical ANS reactivity pattern: relatively lower activity in skin conductance level under demand (attention task) and relatively higher activity, as reflected by the cardiovascular response to neutral stimuli (orienting stimuli), which suggests poor adaptation of ANS arousal to the environment in these schizophrenics. This finding agrees with those reported in other short-term outcome studies that considered differences in ANS activity in a schizophrenic population. The authors' findings indicate that these differences in the ANS response in schizophrenics should be included in future biochemical and pharmacotherapeutic investigations on schizophrenia. PMID- 2885865 TI - Rebound insomnia in neuroleptic drug withdrawal neurophysiologic characteristics. AB - Rebound insomnia is one of the medical effects of reduction in dosage or discontinuation of neuroleptic drugs. The electrophysiologic features of sleep dysfunction are reported and discussed in 3 patients manifesting withdrawal related DIMS. Electrographic anachronism and cyclic alternating pattern are signs of N-Rem sleep dysfunction. Clinical and neurophysiologic data suggest that rebound insomnia in neuroleptic withdrawal is due to an enhancement of physiologic mechanisms and rebound supersensitivity of cholinergic transmission in the ARAS. PMID- 2885866 TI - Treatment of neuroleptic malignant syndrome with dopamine hydrochloride: a case report. AB - A case of neuroleptic malignant syndrome (NMS) is discussed which occurred in a 72-year-old paranoid psychotic patient while on maintainance neuroleptic therapy with penfluridol. A prompt and sufficient improvement in NMS was observed when dopamine hydrochloride (DAHCl) was administered intravenously. It may be possible to explain the effectiveness of DAHCl on the basis of the dopaminergic hypothesis advanced to explain NMS. PMID- 2885867 TI - Neuroleptic profile of cipazoxapine (Savoxepine), a new tetracyclic dopamine antagonist: clinical validation of the hippocampus versus striatum ratio model of dopamine receptors in animals. A preliminary report. AB - Cipazoxapine is a new tetracyclic dopamine antagonist which we tested to validate an animal model for neuroleptics. This model was based on drug affinity to dopamine receptors in hippocampus versus striatum. For haloperidol the ratio was 0.67, for cipazoxapine 0.06. In this preliminary trial on eight schizophrenic patients we found that cipazoxapine in doses between 0.40 and 2 mg had an antipsychotic effect (measured by the BPRS) without extrapyramidal side-effects (measured by the Simpson-Angus-Scale). Our preliminary results thus support the animal findings. PMID- 2885868 TI - Neural control of somatotropic function. PMID- 2885870 TI - Poly-A+ mRNA and defeminization of sexual behavior and gonadotropin secretion in rats. AB - To test the hypothesis that testosterone (T) sexually differentiates gonadotropin secretion and sexual behavior by inducing synthesis of messenger RNA (mRNA), newborn female rats received intrahypothalamic infusions of saline or cordycepin, an adenosine analogue that preferentially inhibits synthesis of polyadenylated mRNA, an hour before they received T propionate (TP) systemically. As adults, controls were anovulatory and did not become sexually receptive when given estradiol benzoate (EB) and progesterone (P). Cordycepin-treated females obtained lordosis quotients (LQs) three times those of controls and most of them ovulated. Cordycepin also curtailed the defeminizing effects of some doses of moxestrol, an artificial estrogen; thus it does not simply block aromatization. Some groups were retested for lordosis using EB and methysergide to bypass P receptors. Methysergide increased LQs in one group that received moxestrol + cordycepin as neonates and that was moderately responsive to P, but it did not increase sexual receptivity among the saline-treated controls. These data suggest that defeminization of sexual behaviour involves more than defeminization of P receptor synthesis. PMID- 2885869 TI - Modulatory effects of adenosine upon the transmitter release in the hippocampal slice preparation of rats. AB - In the hippocampal slice preparation of rats, preloaded with 3H-glutamate a local perfusion technique was used in order to measure the labelled transmitter output. The electrical receptive stimulation of the Schaffer collateral-commissural projections resulted in a detectable 3H-glutamate release which was significantly increased in the presence of 4-aminopyridine (4-AP). Exogenous adenosine and its analogue L-PIA induced a slight unsignificant reduction of the release while in the presence of 4-AP the release was almost completely blocked. Adding adenosine deaminase (ADA) did not change the normal transmitter release while in the presence of 4-AP the elimination of the endogenous adenosine brought about a significantly higher 3H-glutamate output. It is concluded that the adenosine induced presynaptic inhibition of the transmitter release could be a significant mechanism under conditions in which the synaptic activity is abnormally high. This effect seems to be mediated via the A1 adenosine receptor since the D-PIA isomer application has no significant inhibitory effects. PMID- 2885872 TI - [Enthusiasm and work. From the memoirs of a woman activist. 4]. PMID- 2885871 TI - Correlation of circadian changes in tyrosine aminotransferase and tryptophan-2-3 dioxygenase in rat liver to irradiation at different times of the day. AB - Male SPF Wistar rats adapted to a 12:12 h light: dark regimen were irradiated at 3-hour intervals in the course of 24 h with a dose of 14.35 Gy X-rays; 24 h after irradiation or sham irradiation and starvation for the same length of time, and also in fed intact rats, tyrosine aminotransferase and tryptophan-2-3-dioxygenase activity in the liver and the serum corticosterone level were determined. Although lethal irradiation modified the given enzyme activities, it did not abolish their circadian rhythm, evidently in association with the low sensitivity in association with the low sensitivity of the liver to ionizing radiation. In irradiated animals (compared with sham-irradiated animals), the serum corticosterone concentration fell during the light part of the day and at the beginning of the dark part. PMID- 2885873 TI - In vitro amoebicidal testing of natural products; Part 2. Alkaloids related to emetine. PMID- 2885874 TI - Pain management. AB - Successful management of pain can be accomplished in nearly all terminally ill patients. Pain must be assessed in terms of its physical, psychological and social components. Spiritual care and control of environmental factors are just as important as drug therapies. Once the cause of the pain is identified, an individualized plan of treatment can be developed. Nondrug therapies are tried first. When drugs must be used, the pain is treated by regular dosing to prevent recurrent breakthroughs--no PRN orders are used. The pain is blocked and its memory erased so that continued, uninterrupted relief is given. Drug management should provide ease of administration to maintain patient independence, unclouded and normal affect, and minimal troublesome side effects. Anticipatory treatment of expected problems with constipation and nausea should be done. By using a reproducible pain measurement scale, titration of drugs is carried out in a stepwise fashion, increasing dosage or potency until the desired effect is achieved. With multimode therapy, no patient should have to suffer the aching/agony pain cycle of terminal illness with cancer. PMID- 2885875 TI - [Comparative evaluation of the results of insulin treatment of early schizophrenia presenting with pseudoneurotic disorders]. PMID- 2885876 TI - Blood to brain distribution of neuroleptics. AB - Knowledge of the tissue distribution of drugs is important in interpreting other more commonly measured pharmacokinetic parameters, such as levels of drug in blood. For the neuroleptics, studies of blood to brain distribution are few and, due to technical differences between studies, the results are neither consistent within drugs nor comparable between drugs. We estimated the plasma to brain distribution of several common neuroleptics in rats using a single technique, the radioreceptor assay for neuroleptics. At doses that led to plasma levels similar to those achieved in clinical use, brain to plasma ratios ranged from 34 and 22 for fluphenazine and haloperidol, respectively, to 2.2 and 0.97 for thioridazine and mesoridazine, respectively. In general, clinical milligram potency and the favorability of distribution to brain ranked in the same order. These results may explain why such low levels of the high potency neuroleptics and such high levels of the low potency neuroleptics, greater than can be explained by relative differences between the same drugs in potency in vitro, are observed in blood both by radioreceptor and chemical assay techniques. PMID- 2885877 TI - Cerebrospinal fluid amino acid concentrations in chronic schizophrenia. AB - The concentrations of the excitatory amino acid, glutamate, the inhibitory amino acids, glycine and taurine, and the inactive amino acids, glutamine and alanine, were determined in cerebrospinal fluid samples from 12 neurological control and 17 chronic schizophrenic patients. No significant differences were observed in any amino acid between the study groups. Within the schizophrenic group, no differences were observed between paranoid and undifferentiated patients. The concentrations of these amino acids in samples obtained from six schizophrenic patients during drug-free as compared to haloperidol-treatment periods also did not differ. These results do not support the glutamate hypothesis of schizophrenia. PMID- 2885878 TI - Correlates of antimanic response to carbamazepine. AB - Nineteen acutely manic patients were studied in a double-blind trial of carbamazepine in doses averaging 1240 mg/day, achieving blood levels of 10.4 +/- 2.2 micrograms/ml. Clinical improvement in mood and psychomotor components of the manic syndrome was rapid in onset, generally parallel to that observed in previous patients treated with neuroleptics, and was associated with increases in the total hours of nighttime sleep. Compared to the seven nonresponders, the 12 patients who improved were significantly more manic during the baseline placebo period, tended to be more dysphoric, and were significantly more rapid cyclers over their entire course of illness as assessed by episodes in the year before NIMH admission (7.0 +/- 5.6 vs. 2.7 +/- 2.4 in the nonresponders). While improvement was robust in responders, it was not always complete, and some of these patients remained mildly to moderately symptomatic. All seven patients with a negative family history of affective illness in first degree relatives were responders, while those with a positive family history were equally divided. These preliminary data suggest that several predictors of poor response to lithium carbonate (manic severity, anxiety and dysphoria, rapid cycling, and negative family history) may be associated with good antimanic response to carbamazepine. PMID- 2885879 TI - Comparing benzodiazepines using the staircase test in mice. AB - Eleven benzodiazepines were evaluated in the staircase test in mice. The behavioural parameters measured were the number of steps climbed and the number of rears during a 3-min test. Climbing and to a lesser extent rears were enhanced at low doses, whereas both parameters, particularly rearing, were reduced at higher doses. The differential effects of the drugs on the two parameters were used to determine indices of anxiolytic efficacy for each drug where increases in climbing were taken to indicate the onset of anxiolytic activity and decreases in rearing the onset of sedative activity. The compounds could be ranked according to these indices in a manner which appears to reflect their therapeutic profile in man. PMID- 2885880 TI - Tremorous mouth movements in rats administered chronic neuroleptics. AB - Oral movements (OMs) in rats administered chronic haloperidol (HAL) were quantified simultaneously by a human observer and via a computerized video analysis system which monitored the distance between the upper and low lips using TV images. The human observer data indicated that during HAL administration the total duration of OMs was initially decreased, gradually returned to levels slightly above controls, and then increased substantially upon drug withdrawal. The computer records confirmed these findings and further indicated that after prolonged HAL administration a syndrome developed in which large-amplitude OMs remained suppressed but OMs of the smallest detectable amplitudes increased. Upon drug withdrawal, these small OMs increased in amplitude and rhythmicity, developing into repetitive tremors. PMID- 2885881 TI - Two tests in rats for antianxiety effect of clinically anxiety attenuating antidepressants. AB - The effects of mianserin, trazodone, amoxapine, maprotiline, and doxepin were assessed in punishment and pentylenetetrazol drug discrimination paradigms. These two procedures are used to identify antianxiety activity in rats. In the punishment procedure, misanserin produced an inverse dose-related increase in punished responding. The magnitude of the increase in punished responding with mianserin was comparable to that observed with the anxiolytic, buspirone. This effect was not observed with any of the other antidepressants tested. None of the antidepressants were found to be active in antagonizing the discriminative stimulus effects of pentylenetetrazol. In fact, at high doses there was a suggestion that the antidepressants may generalize to the pentylenetetrazol discriminative stimulus. Therefore, several antidepressants with purported clinical antianxiety activity, were not active in two procedures that detect antianxiety activity in rats. PMID- 2885882 TI - Anti-apomorphine effects of phenothiazine drug metabolites. AB - The potencies in producing muscle relaxation, and in antagonizing apomorphine induced climbing and hypothermia in mice, were examined for chlorpromazine, levomepromazine and their main metabolites, and for fluphenazine and 7-hydroxy fluphenazine. 3-Hydroxy chlorpromazine was more potent than chlorpromazine in antagonizing apomorphine-induced climbing, while levomepromazine and 3-hydroxy levomepromazine were equipotent in this test. The 3-hydroxy metabolites of chlorpromazine and levomepromazine were more potent than the parent compounds in antagonizing hypothermia, and had significantly weaker muscle relaxant effects than the parent compounds. The 7-hydroxy and N-monodesmethyl metabolites were generally less potent that the parent compounds in antagonizing apomorphine induced effects. N-Monodesmethyl levomepromazine had a pronounced muscle relaxant effect, like levomepromazine itself. The sulphoxide metabolites of chlorpromazine and levomepromazine were inactive in all tests. Their potencies in these tests indicate that among the metabolites 7-hydroxy chlorpromazine, N-monodesmethyl chlorpromazine and 3-hydroxy levomepromazine, which have all been identified in plasma from patients, may contribute to the antipsychotic effects of the drugs, and furthermore that N-monodesmethyl levomepromazine may contribute to the sedative effects of levomepromazine. PMID- 2885883 TI - Biphasic effect of L-5-HTP in the Vogel conflict model. AB - The effect of L-5-HTP (25 400 mg/kg IP) following inhibition of the peripheral aromatic amino acid decarboxylase by means of benserazide (25 mg/kg IP) was investigated in a test modified from Vogel's drinking conflict model. At 50 mg/kg an anti-conflict action was detected, while higher doses (100-400 mg/kg) decreased punished responding. A lower dose (25 mg/kg) had no effect. Non specific effects--such as alterations in muscle tone, in motivation to drink or in the sensitivity to electrical shock--could not explain the anxiolytic- and anxiogenic-like actions of 50 and 100 mg/kg, respectively. The bi-phasic effect of L-5-HTP is discussed in terms of different subpopulations of central serotoninergic receptors, possibly exerting opposing influences on conflict responding. The study emphasises the importance of 5-HT mechanisms in anxiety, and the possibility of finding novel anxiolytics among drugs selectively affecting central 5-HT neurotransmission. PMID- 2885884 TI - Anxiolytic activity of a brain delivery system for GABA. AB - We evaluated the anxiolytic property of a brain-specific gamma-aminobutyric acid delivery system (GABA-CDS) in male rats by means of a drink-foot shock conflict procedure. Brain-specific delivery of the active compound was achieved by combination of GABA benzyl ester with an interconvertible dihydropyridine in equilibrium pyridinium salt carrier, which is "locked in" to the brain upon its oxidation. Pharmacokinetic studies revealed that the hydrophilic pyridinium salt form (G-Q+) of the GABA-CDS formed in situ remained in the brain for 12 h but was cleared from the blood and other peripheral tissues by 0.5-4 h. While the lipophilic form (G-DH) of the GABA-CDS caused a marked and sustained anxiolytic response when administered systemically, GABA and the charged pyridinium salt (G Q+ form) of the GABA-CDS were ineffective. G-DH was injected at either 0, 4, 10 or 25 mg/kg IV in DMSO after rats were water and food deprived. After either 0.5, 2, 4, 8 or 24 h, rats were permitted 10 s of shock-free drinking of 10% sucrose, then given a 35 mA (DC) current through the drinking tube. Drinking time was recorded for 3 min. All doses of G-DH caused a significant increase in anxiolysis over control levels through 8 h. An increase (4 to 7-fold) in anxiolytic activity was observed through the 10 mg/kg dose with the 25 mg/kg dose causing no additional increase. No sedation or analgesia was observed at 2 h with any anxiolytic-producing dose of G-DH. These results suggest that G-DH elicits anxiolysis with minimal sedation, through the local brain action the G-Q+ or subsequent to the release of GABA. PMID- 2885885 TI - Alzheimer's disease, a multisystem disorder: implications for therapy. PMID- 2885886 TI - Use of neuroleptics, antidepressants, and lithium by U.S. community populations. PMID- 2885887 TI - Noradrenergic mechanisms in akathisia: treatment with propranolol and clonidine. PMID- 2885888 TI - Self-perception of tardive dyskinesia and neuroleptic-induced parkinsonism: a study of clinical correlates. PMID- 2885889 TI - Long-term effects of L-dopa and procyclidine on neuroleptic-induced extrapyramidal and schizophrenic symptoms. PMID- 2885891 TI - Novel drug treatments for schizophrenia. PMID- 2885890 TI - Serum neuroleptic and anticholinergic activity in relationship to cognitive toxicity of antiparkinsonian agents in schizophrenic patients. PMID- 2885892 TI - Assessment and treatment of pervasive anxiety. AB - Definitions of the central symptoms of anxiety disorders are given and these are followed by the principles underlying assessment; a discussion of rating scales for the detection and measurement of morbid degrees of anxiety follows. The important points in assessment prior to therapy are outlined and emphasis is placed on the possibility of distinguishing biogenic (endogenous) anxiety states from the more usual psychogenic forms of anxiety disorder. This distinction is of major importance when devising the therapeutic plan: biogenic depressive states, of which the early stage of panic disorder is one form, are resistant to psychotherapeutic intervention but may respond to treatment with antidepressant drugs. The principles of brief psychotherapeutic intervention are outlined with emphasis on the two central themes underlying successful therapy: the development of self-control and the exposure of the patient to anxiety in the setting of the therapeutic programme. PMID- 2885894 TI - Toward an integrated approach to the treatment of schizophrenia. AB - Long-term outcome studies have shown that schizophrenia is an illness whose course is usually characterized by exacerbations and remissions. This chapter summarizes pertinent literature regarding treatment of acute episodes; early intervention to prevent the development of full relapse; and pharmacological, behavioral, and psychotherapeutic strategies designed to decrease the amount of stress and patients' vulnerability to stress and thus decrease the likelihood of relapse. An emphasis is placed on a comprehensive treatment approach involving continuity of care. PMID- 2885893 TI - Behavioural and drug treatments of phobic and obsessive-compulsive disorders. AB - The two most-used treatments for phobic and obsessive-compulsive disorders are exposure and drugs. In exposure therapy, the patient is persuaded to re-enter the phobia- or ritual-evoking situation and to stay there despite the ensuing panic until it starts to subside, which may take 1 h or more. The patient does this repeatedly and systematically, noting outcome in an exposure-homework diary which the clinician reviews. Controlled studies show that such self-exposure treatment (requiring little time from the clinician) has lasting value. Only a minority of cases need additional therapist-aided exposure. Antidepressants are useful adjuvants to exposure in dysphoric phobics and ritualisers. No antidepressant is clearly superior to any other. Relapse on stopping medication is a problem. Neither beta-blockers nor benzodiazepines are yet of proven lasting value for these syndromes. It is too easy to forget that drugs have unpleasant side-effects which are not seen with exposure therapy. PMID- 2885895 TI - A neuroendocrinological study of responders and non-responders to ceruletide treatment in chronic neuroleptic-resistant schizophrenia. AB - To define the characteristics of chronic schizophrenic patients who had responded poorly to treatment with ceruletide, several neuroendocrinological tests were carried out in 5 responders and 5 non-responders. Both thyroid-stimulating hormone and prolactin responses to thyrotropin-releasing hormone stimulation were within normal ranges in all subjects. The luteinizing hormone response to luteinizing hormone-releasing hormone, was slightly weaker in non-responders. There were no differences in the insulin tolerance test between responders and non-responders. Unusually delayed or prolonged growth hormone response to arginine infusion was observed in non-responders. These findings suggest dysfunction of the hypothalamo-pituitary system, especially of the arcuate nucleus and its functionally related areas, in non-responders. PMID- 2885896 TI - Factors associated with decreased platelet MAO activity in chronic schizophrenics. AB - Platelet MAO activity was determined in a sample of chronic schizophrenics, including drug-free and neuroleptic-treated patients, and in a normal control group. Patients with MAO values below and above the median were compared with respect to several clinical, historical, neuroradiological and neuropsychological variables. The enzyme activity was significantly decreased in the whole patient group and in the subgroup of neuroleptic-treated patients, but not in the subgroup of drug-free patients. The only significant difference between low MAO and high MAO patients concerned drug status (higher percentage of patients on neuroleptics in the former subgroup). On stepwise discriminant function analysis, drug status (on neuroleptics vs. off neuroleptics) correctly classified 63.4% of patients. PMID- 2885897 TI - Adrenocortical steroid secretion and 11-beta-steroid hydroxylase activity after pituitary-adrenocortical probes in depression. PMID- 2885899 TI - The effect of gastrin-releasing peptide on the endocrine pancreas. AB - The 27-amino acid peptide gastrin releasing peptide (GRP-(1-27] was infused at 4 dose levels (0.01, 0.1, 1.0, and 10 nM) into the arterial line of the isolated perfused porcine pancreas. Infusions were performed at 3 different perfusate glucose levels (3.5, 5.0, and 8.0 mM) and at two levels of amino acids (5 and 15 mM). GRP-(1-27) stimulated insulin and pancreatic polypeptide secretion and inhibited somatostatin secretion in a dose-dependent manner. Glucagon secretion was unaffected by infusion of GRP under all circumstances. The effect of GRP-(1 27) on insulin secretion was enhanced with increasing perfusate glucose levels, whereas the effects upon somatostatin and pancreatic polypeptide secretion were independent of perfusate glucose levels. The responses to GRP were unaffected by elevation of the concentration of amino acids in the perfusate. The effects of GRP were unaffected by atropine at 10(-6) M. The localization of GRP within the porcine pancreas, its release during electrical stimulation of the vagus nerve, and its potent effects upon pancreatic endocrine secretion make it conceivable that the peptide participates in parasympathetic regulation of pancreatic endocrine secretion. PMID- 2885898 TI - The role of computed tomography in the management of a case of seminoma in an abdominal testis. PMID- 2885900 TI - Effect of atropine and somatostatin on bombesin-stimulated plasma gastrin, cholecystokinin and pancreatic polypeptide in man. AB - Infusion of the neuropeptide bombesin stimulates the secretion of several gastrointestinal hormones by an unknown mechanism. We have investigated the effects of atropine (15 ng/kg as bolus followed by 2.5 ng/kg X 30 min) and somatostatin (125 micrograms as i.v. bolus followed by 62.5 micrograms/30 min) on the stimulation of 3 hormones (gastrin, cholecystokinin and pancreatic polypeptide) by 60 pmol/kg X 20 min bombesin in 6 healthy volunteers. Plasma samples for measurement of hormones by sensitive and specific radioimmunoassays were obtained at -5, 0, 2.5, 5, 7.5, 10, 15, 20, 25 and 30 min. Bombesin induced significant increases in plasma gastrin (12 +/- 2 to 34 +/- 3 pM; P less than 0.0005), cholecystokinin (1.2 +/- 0.2 to 8.9 +/- 0.7 pM; P less than 0.0001) and pancreatic polypeptide (22 +/- 4 to 72 +/- 19 pM; P less than 0.05). There were great differences between the effects of atropine and somatostatin on the hormonal responses to bombesin. Atropine slightly increased the response of gastrin by 19% and that of cholecystokinin by 15%, but strongly inhibited the bombesin-stimulated pancreatic polypeptide secretion by 97%. On the other hand, somatostatin inhibited the bombesin-induced secretion of gastrin by 48%, cholecystokinin by 82% and pancreatic polypeptide by 107%. These results point to considerable qualitative and quantitative differences in the stimulatory mechanisms of bombesin on the hormones studied. PMID- 2885901 TI - [Drugs and the eye. Ocular reactions to systemic therapy with beta blockers (I)]. PMID- 2885902 TI - [Response of growth hormone to GRF(1-29)NH2 in 12 cases of active acromegaly]. PMID- 2885903 TI - [Epidermal growth factor]. PMID- 2885904 TI - [Bilateral germ cell tumors of the testis]. PMID- 2885905 TI - [Public health in the academic curriculum]. PMID- 2885906 TI - Hepatic tyrosine aminotransferase inhibitor affects the bioavailability of exogenous tyrosine. AB - This study demonstrates the importance of controlling the activity of hepatic tyrosine aminotransferase when tyrosine is administered orally. The specific inhibition of this enzyme is proposed in the clinical use of tyrosine in syndromes related to deficient catecholaminergic transmission. PMID- 2885907 TI - Surfactant synthesis, secretion, and function in alveoli and small airways. Review of the physiologic basis for pharmacologic intervention. AB - Surface-active material is known to lower surface tension at the air/liquid interface and provide alveolar stability. Less well appreciated is the potential role of surface-active material in maintaining the patency of small airways and in transporting particles from the alveolar surface to the small airways. The interactions between the two dominant secretory cells in the terminal lung units, i.e., the alveolar type II cell and the Clara cell, are just starting to be discovered. The biochemical signals for secretion of surface-active material in vivo are still not known. The dominant physiologic stimulus is hyperventilation. Secretion in vitro is stimulated by activation of protein-kinase C (tetradecanoyl phorbol acetate), protein-kinase A (cyclic AMP, beta-adrenergic agonists, cholera toxin), and calcium ionophores (A23187 or ionomycin). The biochemical basis for secretion will be discussed. PMID- 2885909 TI - [Long-term drug therapy of bronchial asthma in childhood and adolescence]. PMID- 2885908 TI - Renal and hemodynamic effects of non-diuretic antihypertensive therapy. PMID- 2885910 TI - Bacterial adherence in the pathogenesis of urinary tract infection: a review. AB - Bacterial adherence to the uroepithelium is recognized as an important mechanism in the initiation and pathogenesis of urinary tract infections (UTI). The uropathogens originate predominantly in the intestinal tract and initially colonize the periurethral region and ascend into the bladder, resulting in symptomatic or asymptomatic bacteriuria. Thereafter, depending on host factors and bacterial virulence factors, the organisms may further ascend and give rise to pyelonephritis. Uropathogens are selected by the presence of virulence characteristics that enable them to resist the normally efficient host defense mechanisms. Considerable progress has been made in identifying bacterial adhesins and in demonstrating bacterial receptor sites on uroepithelial surfaces. Recent studies have identified natural anti-adherence mechanisms in humans as well as possible increased susceptibility to UTI when these mechanisms are defective and when receptor density on uroepithelial cells is altered. Knowledge of bacterial adherence mechanisms may permit alternative methods of prevention and management of urinary infection, including the use of subinhibitory concentrations of antibiotics, vaccine development, nonimmune inhibition of bacterial adhesins and receptor sites, and the use of autochthonous flora, such as lactobacilli, to exclude uropathogens from colonizing the urinary tract. PMID- 2885911 TI - [Acute interstitial nephritis]. PMID- 2885913 TI - Daily drinking and drunken driving. AB - In a study of 3,658 drunken drivers, it was found that eight percent reported daily drinking of alcohol, 82% reported no daily drinking, and 10% gave no information about drinking frequency. Measurement of gamma glutamyl-transferase (a biological marker for heavy drinking) in a selection of blood samples from drunken drivers reporting daily drinking, indicated that the majority of these drivers were heavy drinkers. The drunken drivers who reported daily drinking, had higher blood alcohol concentrations, were responsible for a larger number of previously detected drunken driving offences, and were more prone to being arrested for drunken driving during working days and during daylight hours than other drunken drivers. Among the repeating offenders, it was estimated that 13% would report daily drinking, and 74% would not. PMID- 2885912 TI - Treatment of schizophrenia. AB - Antipsychotic medication remains a mainstay of treatment in both acute and chronic schizophrenia. Emphasis in recent years has focused on maximizing benefits and minimizing risks of medication by attempting to establish minimum effective dosage requirements for all phases of treatment and to provide alternative strategies for individuals who fail to benefit from antipsychotic drug treatment. At present all approaches to the treatment-refractory patient remain experimental, and further research in this area is of critical importance. Definite advances have been made in exploring the impact of psychological and psychosocial treatments administered in conjunction with various antipsychotic drug strategies. More sophisticated and comprehensive assessment measures have been applied in long-term treatment trials, enabling us to be more specific about treatment goals and treatment evaluation. Although no major "breakthrough" has occurred in the treatment of schizophrenia, incremental advances which can reduce rates of relapse and rehospitalization, improve the quality of adaptation, and reduce the risk of significant adverse effects are of enormous importance to affected individuals, their families, and society at large. PMID- 2885914 TI - [Glutamate: a neurotransmitter in the mammalian brain]. PMID- 2885915 TI - [Cerebral osmoreceptors]. PMID- 2885916 TI - Structural evidence for the authenticity of the human retinoblastoma gene. AB - The retinoblastoma (Rb) gene is the prototype for a class of recessive human cancer genes in which loss of activity of both normal alleles is thought to be associated with tumorigenesis. Sixteen of 40 retinoblastomas examined with a complementary DNA probe shown to be the Rb gene had identifiable structural changes of the Rb gene including in some cases homozygous internal deletions with corresponding truncated transcripts. An osteosarcoma also had a homozygous internal deletion with a truncated transcript. In addition, possible hot spots for deletion were identified within the Rb genomic locus. Among those tumors with no identifiable structural changes there was either absence of an Rb transcript or abnormal expression of the Rb transcript. Comparison of the structural changes in the tumor cells and fibroblasts of certain patients provided support for Knudson's two-hit hypothesis for the development of retinoblastoma at the molecular level. The ability to detect germline structural deletions in fibroblasts from some patients with bilateral retinoblastoma also indicates that the isolated gene is useful for diagnostic purposes. PMID- 2885917 TI - erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells. AB - A wide variety of human tumors contain an amplified or overexpressed erbB-2 gene, which encodes a growth factor receptor-like protein. When erbB-2 complementary DNA was expressed in NIH/3T3 cells under the control of the SV40 promoter, the gene lacked transforming activity despite expression of detectable levels of the erbB-2 protein. A further five- to tenfold increase in its expression under influence of the long terminal repeat of Moloney murine leukemia virus was associated with activation of erbB-2 as a potent oncogene. The high levels of the erbB-2 product associated with malignant transformation of NIH/3T3 cells were observed in human mammary tumor cells that overexpressed this gene. These findings demonstrate a new mechanism for acquisition of oncogenic properties by genes encoding growth factor receptor-like proteins and provide a functional basis for the role of their overexpression in the development of human malignancies. PMID- 2885918 TI - Three recessive loci required for insulin-dependent diabetes in nonobese diabetic mice. AB - A polygenic basis for susceptibility to insulin-dependent diabetes in nonobese diabetic (NOD) mice has been established by outcross to a related inbred strain, nonobese normal (NON). Analysis of first and second backcross progeny has shown that at least three recessive genes are required for development of overt diabetes. One, Idd-1s, is tightly linked to the H-2K locus on chromosome 17; another, Idd-2s, is localized proximal to the Thy-1/Alp-1 cluster on chromosome 9. Segregation of a third, Idd-3s, could be shown in a second backcross. Neither Idd-1s nor Idd-2s could individually be identified as the locus controlling insulitis; leukocytic infiltrates in pancreas were common in most asymptomatic BC1 mice. Both F1 and BC1 mice exhibited the unusually high percentage of splenic T lymphocytes characteristic of NOD, suggesting dominant inheritance of this trait. The polygenic control of diabetogenesis in NOD mice, in which a recessive gene linked to the major histocompatibility complex is but one of several controlling loci, suggests that similar polygenic interactions underlie this type of diabetes in humans. PMID- 2885919 TI - AIDS and insects. PMID- 2885920 TI - Who owns the human genome? PMID- 2885921 TI - Full-wave rectification from a mixed electrical-chemical synapse. AB - Electrical and chemical synapses usually reinforce one another, but the pyloric late-to-lateral pyloric (PL-to-LP) neuronal connections in lobster stomatogastric ganglia create an inverted U-shaped transfer function between the two neurons: regardless of whether the PL membrane voltage swings positive or negative, the postsynaptic LP voltage will go negative. When the presynaptic cell voltage goes negative, the effect on the LP voltage is due to electrical coupling. During positive presynaptic voltages, the strong contribution of graded chemical inhibition from the PL to the LP neuron overrides the positive electrical coupling to produce net negativity. PMID- 2885922 TI - [Involvement of dynorphin in the antinociception induced by intrathecal injection of neurotensin in the rat]. PMID- 2885923 TI - [Preventive effect of somatostatin on the secretory function of islet B-cells against the damage produced by streptozotocin]. PMID- 2885924 TI - [Effectiveness of treating patients with pulmonary tuberculosis and alcoholism]. PMID- 2885926 TI - [Comparative analysis of the flexion of metal frameworks in various monolithic and soldered dental alloys]. PMID- 2885925 TI - [Minimal brain dysfunction. III. Treatment (preliminary report)]. PMID- 2885927 TI - [Comparative analysis of teeth reconstructed using 3 types of para-pulp pins with and without prosthetic superstructures]. PMID- 2885928 TI - Comparison of famotidine 40 mg with ranitidine 300 mg at night in short-term duodenal ulcer healing. A South African multicentre study. AB - One hundred and thirty-two patients with endoscopically confirmed duodenal ulcers were entered into a 4-6-week double-blind trial of famotidine (Fm) and ranitidine (Rn). Seventy patients were randomised to Fm 40 mg at night and Rn placebo and 62 to Rn 300 mg at night and Fm placebo. Gelusil tablets were allowed for ulcer pain, and diary cards were issued. Clinical evaluations were carried out on entry and at 2 and 4 weeks, and endoscopy was repeated at 4 weeks. Patients with an unhealed ulcer at 4 weeks were continued on the same treatment for another 2 weeks and further endoscopy was carried out at 6 weeks. The groups were comparable with respect to age, sex, duration of the most recent attack, initial ulcer size and smoking, but the duration of disease tended to be longer in the Rn treated group (P less than 0.05). Of the patients available for analysis, 75% of the Fm-treated and 78% of the Rn-treated patients were healed at 4 weeks and 91% of patients in both treatment groups were healed at 6 weeks. Gelusil consumption and symptomatic responses were comparable in the two groups, and no side-effects were noted apart from mild dizziness in 1 patient after a single Fm tablet. The mean initial size of ulcers healed at 4 weeks was significantly less than that of ulcers which were unhealed at 4 weeks (P less than 0.01), and the healing rate among smokers was significantly lower than that among non-smokers--48 of 72 patients (67%) and 41 of 45 (91%) respectively (P less than 0.01). The study shows that Fm 40 mg at night is as effective as Rn 300 mg in duodenal ulcer healing. PMID- 2885929 TI - Current status of beta-blockers in black hypertensive patients. PMID- 2885930 TI - Major ambulatory surgery of the pediatric patient. AB - Ambulatory surgery is an important part of the surgical care of children. Experience with 6972 pediatric surgical procedures performed in the Surgicenter is reviewed. Surgical techniques for the most common procedures--inguinal herniorrhaphy, orchiopexy, and umbilical herniorrhaphy--are described. PMID- 2885931 TI - Ophthalmic beta-blockers since timolol. AB - In the twenty years since beta-blockers were proposed for treatment of glaucoma, use of topical timolol has increased to account for 70% of all glaucoma medications used. The objective of this article is to review the "newer" beta blockers, and to address the generalization that "all ophthalmic beta-blockers are the same." The review concentrates on agents that have been studied as topical treatments for patients with elevated intraocular pressure. Sections on pharmacology and design of clinical trials are included to aid the ophthalmologist in evaluating the new drugs and published clinical reports. The major questions to consider in evaluating the therapeutic potential of a new beta blocker for the treatment of glaucoma involve efficacy and safety: Is the drug as effective as timolol? Does it have a duration of action at least as long as timolol? Does it have ocular toxicity? Is it comfortable? What are its systemic effects? PMID- 2885932 TI - [AIDS--placed in an international future perspective]. PMID- 2885933 TI - [Various problems in the diagnosis and treatment of the broncho-obstructive syndrome]. AB - Clinico-x-ray-laboratory investigation, bronchoscopy were performed, respiratory function and ECG were studied in 212 patients with different forms of chronic bronchitis. Six groups of patients were defined with relation to the presence or absence of obstruction, its nature (permanent, transient), prevalence (small, medium and large bronchi), genesis of disease (inflammatory, allergic). The characteristics of the groups and their clinico-x-ray, functional and immunological features were presented. Treatment including methods of climatotherapy, exercise therapy, pharmacological agents (antibacterial, broncholithic and antihistaminic), physiotherapy and administered with relation to the defined groups, proved to be effective. The improvement of bronchial permeability was noted in 49.5% (ranging from 40.0 to 68.7% in different groups). PMID- 2885935 TI - Memorial service for Alexander Hollaender, Washington Cathedral, December 12, 1986. PMID- 2885934 TI - [Correction of hemodynamics in patients with acute pneumonia]. AB - Patients with acute pneumonia demonstrate disturbance of myocardial contractility manifesting itself in an increase of end diastolic and systolic volumes, a decrease in the ejection fraction and circular myocardial contractility rate. In a raised level of mean arterial pressure i.v. administration of strophanthin in acute pneumonia can produce a negative effect in the form of a decrease in the stroke volume and cardiac output. Myofedrin promotes an increase in cardiac ejection and can be used for therapy of patients with acute pneumonia to correct hemodynamics. PMID- 2885936 TI - An evaluation system for ranking chemicals with teratogenic potential. AB - An evaluation system has been developed which permits comparison of the relative toxicity of chemicals based on their potential to alter embryonal and early-stage fetal development. It was considered necessary, from a regulatory standpoint, to develop a system for ranking chemicals which possess teratogenic potential. A detailed discussion of the various parameters selected and their relative importance is provided. PMID- 2885937 TI - Effect of ethylene glycol monomethyl ether on spermatogenesis, dominant lethality, and F1 abnormalities in the rat and the mouse after treatment of F0 males. AB - Adult male CD rats and CD-1 mice were given a single oral dose of ethylene glycol monomethyl ether (EGM) at 0, 500, 750, 1,000, or 1500 mg/kg. Groups of 10 were killed at weekly intervals after dosing for analysis of sperm counts and morphology or testicular histology; further groups of 10 were sequentially mated to pairs of virgin females to test for dominant lethality or gross foetal malformations in the F1 generation (F1 abnormalities). EGM was found to deplete the spermatocytes of both species severely, principally pachytene cells, but with other stages affected with increasing dose. A delay in the progression of spermatogenesis may account for a discrepancy between the apparent stage specificity of damage deduced from lowered sperm counts and that observed histologically. In the rat, morphological abnormalities were observed in sperm that had been exposed as spermatocytes; in the mouse, however, the sensitive cells were the late spermatocytes and early spermatids. In all these parameters there was an indication of a dose-response relationship in both rats and mice. In the mating studies EGM induced a dose-related decrease in fertility 5 weeks after dosing in the rat, but complete sterility in all but the lowest dose after 6 weeks. In contrast, EGM had no effect on the reproductive capacity of the mouse. There was no statistically significant evidence for the induction of dominant lethal mutations or F1 abnormalities in either species. A single oral dose of cyclophosphamide (CTX) at 100 mg/kg induced a significant increase in dominant lethality in both species. CTX reduced the number of total implants in the rat and induced a nonsignificant increase in the number of abnormal offspring sired by treated male mice. PMID- 2885938 TI - Correlations between embryotoxic and genotoxic effects of phenytoin in mice. AB - The anticonvulsant drug phenytoin (DPH) has been suspected to produce embryotoxicity through an arene oxide intermediate. This drug was also found to be a genotoxic agent. These hypotheses were tested in pregnant mice modulating the phases I and II metabolizing enzymes. DPH was studied by assessing embryotoxicity, teratogenicity, and genotoxicity, the latter by the micronucleus test on the polychromatic erythrocytes of dams and fetuses. DPH embryotoxicity was potentiated by inhibiting both cytochrome P-450 and epoxide hydrase and decreased by inducing cytochrome P-450. Equivocal results were obtained by modulating cytochrome P-448. The main DPH metabolite, p-hydroxyphenytoin (HPPH), was ineffective both per se and after cytochrome induction or epoxide hydrase inhibition. DPH did not exert genotoxicity on the maternal organism, no matter which modulating agent was used. In the fetus, however, weak genotoxic effects were observed. These effects significantly increased with inhibition of epoxide hydrase; they disappeared with induction of both cytochromes P-448 and P-450 or with inhibition of the latter. No genotoxicity was exerted by HPPH, even when the enzymatic pattern was modulated. It is concluded that the major role in DPH embryotoxicity is played by the unchanged drug, while the presence of the arene oxide is determinant for genotoxic effects. PMID- 2885939 TI - Potentiating effect of caffeine on embryotoxicity of cyclophosphamide treatment in vivo during the preimplantation period. AB - Since it is unknown if chemicals which are generally safe in pregnancy can potentiate the embryotoxicity of cytotoxic drugs before implantation, the combined effects of cyclophosphamide (CPA) and caffeine (CF) were studied in the mouse (day 2) with CPA at 20 mg/kg, which induces a 18% resorption rate, and CF at 100 mg/kg, which does not increase embryolethality. The embryotoxicity of CPA did not increase when CF was either given 6 h before or simultaneously with CPA on day 2. However, when CF was given 6 h after CPA, a potentiated increase of embryolethality was observed at term and of structural chromosomal aberrations in embryos even before implantation, while sister chromatid exchange (SCE) frequency was less increased than after single CPA treatment. The results demonstrate the importance of pharmacokinetics in pregnancy even before implantation. Furthermore, since SCE may not only indicate DNA damage but also repair, the reduced SCE rate and the increase in structural chromosome aberrations suggest that CF can inhibit the repair of CPA-induced DNA damage in preimplantation embryos. Finally, for the first time the data are providing evidence that CF at subthreshold doses can potentiate the embryotoxicity of an alkylating agent in vivo even before implantation. PMID- 2885940 TI - DNA damage in the central nervous system of rats after in vivo exposure to chemical carcinogens: correlation with the induction of brain tumors. AB - The alkaline elution technique has been used to evaluate DNA damage in brain of rats treated with a single equimolar dose of 14 carcinogens of different chemical structure. A clear-cut increase of DNA elution rate, which is considered indicative of DNA fragmentation, was produced by 10 compounds known to induce the development of tumors in the rat central nervous system: N-nitroso-N-methylurea, N-nitroso-N-ethylurea, N-nitroso-N-butylurea, N-nitroso-N-methylurethane, methyl methanesulfonate, ethyl methanesulfonate, dimethyl sulfate, diethyl sulfate, 1,3 propansultone, and procarbazine. Similar amounts of DNA fragmentation were produced by both potent and weak brain carcinogens. In contrast, any significant increase of DNA elution rate was absent in rats treated with N-methyl-N'-nitro-N nitrosoguanidine, N-nitrosodimethylamine, N-nitrosodiethylamine, and beta propiolactone, all of which are devoid of carcinogenic activity for the rat central nervous system. These results suggest that the described in vivo brain DNA damage/alkaline elution assay deserves further studies on a wide number of carcinogens and noncarcinogens aimed to establish its possible usefulness for a qualitative preliminary assessment of the ability of a compound to induce neurogenic tumors. PMID- 2885942 TI - Agent orange and risks to reproduction: the limits of epidemiology. PMID- 2885941 TI - Cyclophosphamide-induced cytogenetic effects in mouse bone marrow and spleen cells in in vivo and in vivo/in vitro assays. AB - Sister chromatid exchange (SCE) and chromosomal aberration studies have been used to monitor human populations for genotoxic exposure to chemical substances. These monitoring techniques involve collection of blood and/or bone marrow from the exposed subjects and culturing cells for one or two cell cycles with various treatments in culture. The results obtained from such in vivo/in vitro studies may lead to an over- or underestimation of the damage that could occur in vivo. In the present study, which uses a mouse model, the in vivo/in vitro cytogenetic assays (SCEs and chromosomal aberrations) have been compared with similar in vivo systems in bone marrow and spleen cells treated with various doses of cyclophosphamide (CPA). The results indicate a significant difference in CPA induced cytogenetic endpoints between in vivo and in vivo/in vitro conditions in both organs. However, linear relationships were found between CPA dose and cytogenetic end point analyzed under both conditions. Based on these results it appears that the in vivo/in vitro assay is a useful technique for indicating potential in vivo damage of chemicals. PMID- 2885943 TI - Genotype assignment of haemophilia A by use of intragenic and extragenic restriction fragment length polymorphisms. AB - We performed DNA analysis in 20 families with haemophilia A in order to evaluate its usefulness for carrier detection and prenatal diagnosis. The polymorphic BclI site within intron 18 of the factor VIII gene and the extragenic TaqI and BglII polymorphic sites which are detected by the random DNA probes designated St14 and DX13, respectively, were investigated for. Two events of recombination were found between the St14 and the haemophilia A locus in 51 informative meioses. In one of these recombinant meioses crossing over had also occurred between the DX13 and the haemophilia A locus. No further crossovers between the DX13 and the haemophilia A locus were found in 20 informative meioses. Segregation analysis of the polymorphic markers and the deleterious mutation within the families allowed a diagnosis at the gene level for 52 out of 57 potential carriers. The new method considerably decreased the uncertainty about carriership for seventeen of the nineteen women with a probability of carriership between 5% and 95% based on pedigree analysis and factor VIII assays. In seven cases chromosome and DNA analysis of a chorionic villus biopsy was carried out. Three of the fetuses were female, four were male. Three of the male fetuses had inherited the normal maternal X-chromosome and were, therefore, not affected. For another male fetus no diagnosis at the gene level was possible since the mother was homozygous for all the known restriction fragment length polymorphisms within or closely linked with the haemophilia A locus. PMID- 2885944 TI - [H2 receptor antagonist treatment and stomach cancer]. PMID- 2885945 TI - Characterization of DR blank alleles by restriction fragment length polymorphism (RFLP). AB - Using a combination of conventional DR serology and RFLP analysis of DR beta and DQ beta, we have been able to identify two different types of DR antigens which belong so far to the DR blank group. The antigen DR-LOT is found on a haplotype A29, Bw60, Cw3, DRblank, DRw52, DQw1. The DR beta-EcoRI RFLP pattern of this haplotype is different from the patterns observed for DR1, DR2, DR3, DR4, DR5, DRw6, DR7, DRw8, DRw9, DRw10, and appears to be composed of a combination of DR2 and DRw6. The DQ beta-EcoRI pattern shows that this haplotype carries the DQw1 split DQR2.6. The second DR blank antigen which we found in a total of five individuals (three unrelated persons and two parents) on B35 positive haplotypes is characterized by a DR beta-EcoRI RFLP pattern indistinguishable from DR1 and by negative reaction with anti-DR1 sera. This antigen appears to be identical to what has been described by Cambon-Thomsen et al. (1986) and Bidwell et al. (1985) as HLA-DR-BON and DR"BR" respectively. We have demonstrated that this antigen is in strong linkage disequilibrium with the DQw1 split DQR1. PMID- 2885946 TI - Multicenter trial of hemodilution in acute ischemic stroke. I. Results in the total patient population. Scandinavian Stroke Study Group. AB - Hemodilution by the combination of venesection and dextran 40 administration has previously been reported to enhance neurologic recovery in the acute phase of ischemic stroke. To study this therapeutic principle in its "natural habitat," a stratified and randomized multicenter trial involving 15 large and small hospitals was performed. Patients with acute ischemic stroke of less than 48 hours' duration and with hematocrits of 38-50% on admission were randomized to a hemodilution (183 patients, mean age 72.0 years) or a control group (190 patients, mean age 71.6 years). The two groups did not differ in sex distribution or medical history. Hematocrit, blood pressure, and neurologic score were closely similar at entry. By graded venesection (250-1000 ml) during the first 2 days and dextran 40 infusions (500 ml daily) during 5 days, the mean hematocrit was reduced from 44.2 to 37.1%. Three-month survival expressed as life table product was 0.84 in hemodilution and 0.88 in control patients. In survivors, neurologic score and activities of daily living performance during 3 months of follow-up were not improved by hemodilution. Length of stay in an acute-care hospital and the need for long-term institutional care was not reduced among patients in the hemodilution group. Major cardiovascular events occurred somewhat more often and there was an apparent increase in mortality during the first few days of hemodilution therapy. However, the differences were not significant. We conclude that the present standardized treatment with moderate hemodilution has no overall beneficial effects in general patients with acute ischemic stroke. PMID- 2885947 TI - Opioid peptide levels in gerbil brain after transient ischemia: lasting depletion of hippocampal dynorphin. AB - Peptides derived from each of the 3 endogenous opioid precursors were measured in gerbil brain regions at various times after transient bilateral carotid artery occlusion using radioimmunoassays specific for beta-endorphin-, met-enkephalin-, and dynorphin A-related peptides. Lasting changes were observed only in the hippocampus. The most striking effect was on dynorphin A immunoreactivity, which was reduced by 30-40% as early as 1 hour after recirculation and remained at 50% of the control level for at least 1 week. In some experiments dynorphin levels showed a transient recovery at 24 hours. These results demonstrate a unique sensitivity of the dynorphin-containing dentate granule cell-mossy fiber pathway to transient ischemia. Although these cells remain histologically intact, the decrease in dynorphin level precedes and continues during the delayed loss of hippocampal CA1 neurons characteristic of this model and further defines the selective vulnerability of hippocampal circuitry following ischemia. These observations clearly identify the hippocampus as a well-defined brain region in which further studies of the postischemic pathophysiology of endogenous opioid peptides may provide a rational basis for evaluating the place of opiate pharmacology in stroke treatment. PMID- 2885948 TI - Virus isolations from mosquitoes collected during the 1982 Japanese encephalitis epidemic in northern Thailand. AB - From 16 June to 15 August, 1982 CDC light traps were used to collect mosquitoes in the province of Kamphaengphet, N. Thailand. 353,042 mosquitoes comprising 59 species were collected and identified, and 345,173 were placed in pools for attempted virus isolation by inoculation of C6/36 Aedes albopictus mosquito cell cultures. Viruses were isolated from 63 mosquito pools. These comprised 56 flaviviruses, identified as 35 isolates of Japanese encephalitis (JE) virus strains, 18 strains of Tembusu (TEM) virus and three untyped flaviviruses (FLA); three alphaviruses, identified as the first isolates of Getah (GET) virus to have been made in Thailand; and four viruses which are still unidentified. Most virus isolates were from Culex tritaeniorhynchus mosquitoes collected in carbon dioxide baited light traps. JE virus was isolated only over a ten-day period and the last isolate was obtained one week before the peak of admission of human encephalitis cases at Kamphaengphet Provincial Hospital. Rapid screening of isolates grown on Ae. pseudoscutellaris (LSTM-AP-61) mosquito cells by indirect immunofluorescence using flavivirus group-specific and JE-specific monoclonal antibodies showed a high degree of correlation with plaque reduction neutralization tests. An antigen capture enzyme immunoassay (EIA) test successfully identified about 50% of the JE virus positive pools, but the method saved considerable processing time. PMID- 2885949 TI - A dot immunobinding assay (DIA) on nitrocellulose membrane for the serological detection of antibodies to Entamoeba histolytica. AB - A rapid, cheap, simple and specific serological test of adequate sensitivity for detecting IgG antibodies against Entamoeba histolytica antigen is described. Axenically cultured amoebic antigen was used to precoat the nitrocellulose membrane. The strips were incubated with test samples and later with horseradish peroxidase (HRPO) labelled protein-A conjugate. A dark blue spot was obtained by treatment with peroxidase substrate, 4-chloro-1-naphthol, in positive samples. Serum samples from 32 healthy controls, 45 patients with acute amoebic liver abscess and 10 asymptomatic E. histolytica cyst passers were tested. This test was positive in 93% of cases of amoebic liver abscess, 3% of healthy controls and none of the cyst passers; its sensitivity (97%) and specificity (93%) were as good as that of the ELISA test and, because it is simple, quick and cheap it is recommended as a serological test of choice for the diagnosis of invasive amoebiasis. PMID- 2885950 TI - Seroepidemiology of E. histolytica infection in Hyderabad. PMID- 2885951 TI - Pancreatic apudomas. PMID- 2885952 TI - [Subcellular localization of glutamine synthetase activity in carp muscle tissue and liver]. AB - Subcellular distribution of the glutaminesynthetase activity (EC 6.3.1.2) is studied in muscle tissue and liver of carp. It is established that this activity is distributed by subcellular fractions analogously to the glutamatedehydrogenase activity--enzyme-marker activity of mitochondria. An additional evidence for the association of the two given enzymes is obtained during equilibrium density gradient centrifugation of mitochondria on 30-60% gradient of sorbitol. Comparison of the obtained results with data from literature testifies to a coincidence of the subcellular localization of the processes of ammonia formation and binding into glutamine, thus confirming a view of the leading role of glutaminesynthetase in ammonia detoxication in carps. PMID- 2885953 TI - [Surgical treatment of undescended testis, orchiopexy or orchiolysis]. PMID- 2885954 TI - [Tardive dyskinesias. Epidemiology and physiopathology]. PMID- 2885955 TI - [Paradoxal neurological side-effects of neuroleptics. Classification and occurrence]. PMID- 2885956 TI - [Delayed manifestations after acute oxygen deficiency in the cerebral white matter]. PMID- 2885957 TI - [A new aerosol adrenergic bronchodilator, procaterol. Comparative study of salbutamol and procaterol]. PMID- 2885958 TI - Long-range and molecular mapping of the human major histocompatibility complex. PMID- 2885959 TI - Identification of two binding sites for atrial natriuretic factor in endothelial cells: evidence for a receptor subtype coupled to guanylate cyclase. PMID- 2885960 TI - A study of genetic linkage heterogeneity in adult polycystic kidney disease. AB - The mutation for APKD has previously been localized to chromosome 16 by the demonstration of genetic linkage with both the alpha-chain of hemoglobin and phosphoglycolate phosphatase. These studies were carried out, however, on a limited number of families, and the possibility remained that mutations at other genetic loci might produce the disease. Such genetic heterogeneity of linkage would invalidate the general use of chromosome 16 markers for the purpose of detection of the disease and complicate the characterization of the APKD mutation at the molecular level. Therefore, further families were studied to resolve this issue. A total of 27 Northern European pedigrees were analyzed, all apparently unrelated and with origins in England, Scotland, Holland, and Eastern Finland. No evidence was found to suggest heterogeneity of genetic linkage between alpha globin and the disease locus in this population. PMID- 2885961 TI - Equine testicular interstitial cell tumors. AB - Interstitial cell tumors from nine stallions were described. In all but one horse the tumors were found in undescended testes. Five animals had bilateral tumors. Two animals showed increased aggression. Tumors contained two cell types. The first type were large distinctly bordered eosinophilic cells interpreted to be hyperplastic and hypertrophic interstitial cells. They blended with pleomorphic often spindloid neoplastic cells which had fibrillar, vacuolated cytoplasm and indistinct cell borders. This latter cell population was arranged in nodules or broad sheets as endocrine-like packets or interweaving fascicles. Biologic behavior of the neoplasms could not be ascertained from histologic examination. PMID- 2885962 TI - Some bacterial diseases of spotted deer (Axis axis). PMID- 2885963 TI - Injection site reactions and antibody responses in sheep and goats after the use of multivalent clostridial vaccines. AB - Uncertainty concerning the use, efficacy and possible adverse effects of clostridial vaccination in goats prompted a study of the injection site reactions and antibody responses in 40 goats and 40 sheep. The vaccines used were Covexin 8, Heptavac and Tasvax 8. In all the animals swellings averaging 2.5 cm in diameter were present at the injection site seven days after vaccination and were still apparent 28 days after vaccination. The injection site reactions could not be attributed to faulty vaccination technique because they did not occur in a control group injected with sterile water. By 14 days the reactions were significantly larger in sheep than in goats and by 28 days the reactions to Covexin 8 were larger than those to the other vaccines in sheep and goats. Serum antibody was present in all groups before vaccination and, with the exception of the goats vaccinated with Heptavac, increased 14 days after vaccination. The increase was greater in sheep than in goats. By 28 days antibody levels had declined in all but the sheep vaccinated with Heptavac in which a further increase occurred. At that time, the antibody levels in vaccinated sheep were still higher than in the unvaccinated sheep whereas the antibody levels in vaccinated goats were no longer different from those in the control goats. These results suggest that there is a difference between the vaccines used and between the responses of the two species and support the clinical observation that the protection afforded to goats by multivalent clostridial vaccines is poorer than that afforded to sheep. PMID- 2885964 TI - Future developments in the manipulation of growth in farm animals. AB - The anabolic steroid and antimicrobial growth promoters may be regarded as the first generation of animal growth promoters or performance enhancers. There is major investment in the development of new techniques to improve the efficiency of farm animal production. These techniques are reviewed under the headings of growth hormone (somatotrophin) and related techniques, immunological techniques, the beta-adrenergic agonists and the direct genetic manipulation of farm animals. PMID- 2885965 TI - Determination of the potency of outdated ipecac using high pressure liquid chromatography and its clinical significance. PMID- 2885966 TI - The clinico-pathological expressions of Epstein-Barr virus infection in lymphoid tissues. PMID- 2885967 TI - Freeze-fracture features of epithelioid cells, multinucleated giant cells, and phagocytic macrophages. Investigations using the model of experimental autoimmune (anti-TBM) tubulo-interstitial nephritis. AB - The freeze-fracture morphology of epithelioid cells, multinucleated giant cells (Langhans' type), and phagocytic macrophages was investigated. The intensely folded and interdigitating surface membranes of epithelioid cells and multinucleated giant cells displayed no specialized areas of cell contact. The size of the intramembranous particles (IMP) and the fact that the area density of IMPs was higher in the cytoplasmic (P) faces than in the external (E) faces of the cell membranes agreed with observations in other eukaryotic cells. The area densities of the IMPs suggest lower transport rates of molecules across the cell membranes of granuloma cells than of certain epithelial cells. Small pits were detected in the surface membranes of the granuloma cells but an extrusion of granules was not observed. The cytoplasmic granules displayed very different sizes and shapes ranging from spherical to rod-shaped. The latter type of granules (probably primary lysosomes) dominated in multinucleated giant cells. The granule membranes were studded with IMPs whose area densities increased with the granule size. Multilamellar bodies with smooth (lipid) fracture faces were found only in phagocytic macrophages. The nuclear pores of the granuloma cells were distributed over the entire surfaces of the nuclei and displayed moderate clustering. The values of the area densities of the nuclear pores were in keeping with the values observed in mammalian and human epithelial or mesenchymal cells, indicating similar exchange rates of molecules between the nucleoplasm and the cytoplasm in these different cell types. In a single phagocytic macrophage the E face of the inner membrane of the nuclear envelope displayed a network of fine filaments whose nature is at present unknown. PMID- 2885968 TI - The influence of the estrous cycle on the volume density and appearance of collagen containing vacuoles in fibroblasts of the rat uterus. AB - The influence of the estrous cycle on the number of intracellular collagen containing vacuoles (CCVs) has been studied in the uterus of the virgin Wistar rat. CCVs seem to be involved in two processes. Translucent CCVs dark CCVs and dark residual bodies appear to be involved in collagen uptake and degradation, whilst the so-called filamentous bodies (FBs), which are large structures filled with amorphous filaments may be concerned with collagen synthesis. The volume density of these FBs is influenced by the estrous cycle and peak values are accompanied by the highest values of extracellular collagen. PMID- 2885969 TI - Short-term inhibition of cellular autophagy by isoproterenol in the submandibular gland. AB - The present study examines the short-term (i.e. 10 min after injection) influence of isoproterenol on cellular autophagy in the rat submandibular gland. The volume fraction of autophagic vacuoles was significantly reduced, suggesting that an anticatabolic reaction, namely inhibition of cellular autophagy, is an early and significant event in the growth of the submandibular gland which is known to occur with long-term isoproterenol treatment. PMID- 2885970 TI - Effects of colchicine on the hepatocellular transport of indocyanine green in the rat. AB - The effects of colchicine on plasma elimination and biliary excretion of indocyanine green (ICG) and sulfobromophthalein (BSP) in rats were examined. Elimination of two different doses of ICG (6 mg and 20 mg/kg body weight) from plasma was significantly delayed when rats were treated with colchicine (3 mg/kg body weight) 3 h prior to the administration of the dye. On the other hand, disappearance of BSP (100 mg/kg) from plasma was not influenced by colchicine. The fact that the difference in the ICG elimination from plasma between colchicine-treated and saline-treated rats was minimal in the early period (i.e., 2 min after administration of the dye), but evident after its half-life (i.e., 10 min, when 6 mg/kg body weight of ICG was given), suggested that colchicine mainly affected the hepatocellular transport of ICG rather than the uptake of the dye by hepatocytes. Colchicine also significantly reduced the excretion of ICG (6 mg and 20 mg/kg) into bile but did not alter that of BSP (100 mg and 200 mg/kg). On the other hand, the same amount of lumicolchicine (3 mg/kg) did not have any effect on the biliary excretion of ICG. These results suggested that ICG is transported through hepatocytes into bile with the aid of the cytoplasmic microtubular system, whereas BSP is handled by hepatocytes in a different way. PMID- 2885971 TI - Expression and regulation of glycogen phosphorylase in preneoplastic and neoplastic hepatic lesions in rats. AB - Glycogen phosphorylase (PHO) was demonstrated immunocytochemically and enzyme histochemically in cryostat sections of liver from rats treated for 7 weeks with N-nitrosomorpholine (120 mg/l and 200 mg/l drinking water) and from untreated controls. The activity and distribution of PHO protein were studied in normal liver and correlated with morphologically defined stages of hepatic tumour development. In normal liver the amount of enzyme protein, as visualized by the immunoperoxidase method using antibodies against phosphorylase, showed some heterogeneity within the liver lobule. The intralobular and intracellular distribution of PHO protein was the same as that of glycogen, namely coarse and granular in periportal hepatocytes and very fine in perivenular cells. In glycogen storage foci the amount of PHO protein was increased. In contrast, PHO activity was generally decreased. In other preneoplastic and neoplastic lesions such as mixed cell foci, neoplastic nodules and hepatocellular carcinomas, PHO protein was increased in all glycogen-loaded cells while PHO activity was reduced. In all glycogen-poor and basophilic cells, both PHO protein and PHO activity were decreased or absent. It was concluded that the decrease in PHO activity in glycogen storage foci was not the direct consequence of genetic changes leading to a loss in enzyme protein but was due to a defect in the cascade of phosphorylation processes resulting in active PHO. Alteration in gene expression leading to a loss of PHO protein was a late event in the process of hepatocarcinogenesis. PMID- 2885972 TI - Granular cell tumors: evidence for heterogeneous tumor cell differentiation. An immunocytochemical study. AB - Eighteen granular cell tumors from various sites were examined with antisera directed against protein S-100, neuron specific enolase (NSE), alpha-1 antichymotrypsin, and alpha-1-antitrypsin, glial fibrillary acidic protein (GFAP), lysozyme, factor VIII-related antigen, myoglobin and vimentin, as well as with a monoclonal antibody (lu-5) directed against a panepithelial marker. The immunocytochemical reaction pattern of the tumors was heterogeneous. The brain and pituitary tumors and one thyroid tumor reacted for alpha-1-antichymotrypsin and alpha-1-antitrypsin, but not for S-100 protein and NSE. However, tumors from other sites showed immunoreactions for S-100 protein and NSE and some also for vimentin. Reactions for alpha-1-antichymotrypsin and alpha-1-antitrypsin were not observed. All other reactions were similarly negative. We conclude that the morphologically homogeneous group of granular cell tumors is biologically heterogeneous. PMID- 2885973 TI - Biologic characterization of human bone tumors. VI. The aneurysmal bone cyst: an enzyme histochemical, electron microscopical, and immunohistological study. AB - The etiology of aneurysmal bone cyst is still unknown. Most theories of the histogenesis of this lesion assume a vascular origin and speculation has focused on the characteristic pseudoendothelial lining of the cyst walls. In the present study, this structure has been subjected to enzyme histochemical, electron microscopical, and immunohistochemical investigation. Of the enzymes tested only alkaline phosphatase was present in the cyst lining. Electron microscopy revealed fibroblast-like cells covering the walls of cystic cavities, but no genuine endothelium, basement membranes or pericytes were identified. For the immunohistochemical studies a panel of poly- and monoclonal antibodies against HLA-DR antigens, mature and immature macrophages/histiocytes, smooth muscle fibers and endothelial cells, as well as the lectin Ulex europaeus I agglutinin were used. None of these markers demonstrated the presupposed vascular characteristics in the cells constituting the pseudoendothelial lining of the cyst walls. Despite current theories to the contrary, it was concluded that aneurysmal bone cyst is unlikely to originate from the vascular system, and that a new concept of its pathogenesis must be sought. PMID- 2885974 TI - Confronting cisternae in pituitary gland thyrotrophs of congenitally hypothyroid mice. AB - Confronting cisternae were found in pituitary thyrotrophs of congenitally hypothyroid mice. These confronting cisternae rapidly reverted back to ordinary rough endoplasmic reticulum following thyroxine administration. Confronting cisternae were not observed in the thyrotrophs of euthyroid control mice. Our results strongly suggest that confronting cisternae are a peculiar form of rough endoplasmic reticulum which appears under certain conditions of enhanced cellular metabolism. PMID- 2885975 TI - [Effect of increased concentrations of oxygen and carbon dioxide in the air on the status of the cardiorespiratory system]. PMID- 2885976 TI - [Characteristics of the effect of 2-pyrrolidone acetamide (piracetam) on energy coupling in rat skeletal muscle mitochondria during cold stress]. AB - Effects of 2-pyrrolidone acetamide (piracetam) on energetic state of mitochondria were studied in skeletal muscles of intact and ovaryectomized rats under conditions of drastic cooling (4 min swimming at 10 degrees). Readministration of piracetam was shown to cause uncoupling of oxidation and phosphorylation in mitochondrial respiratory chain (a decrease in respiratory control by Chance), as well as the drug increased the rate of O2 consumption in presence of oligomycin and decreased the uncoupler stimulating action on respiration in the group of intact animals. The alterations observed were most distinct in rats with cold stress, which was followed by piracetam administration, except of the rate of respiration stimulation, distinctly increased in presence of uncoupler. Piracetam did not exhibit any noticeable effects on the patterns of respiration studied in skeletal muscles of ovaryectomized rats. Protective properties of piracetam in cooling are discussed. PMID- 2885977 TI - Transmission of human T cell lymphotropic virus type I by blood transfusion before and after mass screening of sera from seropositive donors. AB - The human T cell lymphotropic virus type I (HTLV-I) is transmitted by blood transfusions that contain cell components as one of the virus transmission modes. We carried out mass screening of sera from seropositive donors by a gelatin particle agglutination test to prevent the spread of HTLV-I by transfusion. Seroconversion rates were compared before and after screening. The results show a remarkable decrease in the rate of infection from 53.6 to 0.9%. Therefore, it is certain that screening by the agglutination method prevents the spread of HTLV-I transmission in blood transfusions. PMID- 2885978 TI - [Specific therapy of acute benzodiazepine poisoning using flumazenil (Ro 15 1788)]. AB - In 20 patients with coma (grade 4: n = 7, grade 3: n = 8, grade 2: n = 2, grade 1: n = 3) due to benzodiazepine intoxication, solely or combined with alcohol or other psychoactive drugs, the effect of a specific benzodiazepine antagonist, Flumazenil (Ro 15-1788), was evaluated. In terms of coma depth, 80% of the patients responded to application of 1.96 mg Flumazenil as a mean with immediate awakening or improvement of at least two steps in coma grading. In those 3 patients, who failed to respond to Flumazenil, the history revealed amitriptyline or barbiturates to be responsible for the comatose state. The observed side effects of Flumazenil included increase (n = 4) or decrease (n = 3) of blood pressure, increase of heart rate (n = 7), cutaneous flush (n = 1) and ventricular extrasystoles (n = 1). Agitation and generalized convulsions, each observed in 1 patient, presumably were due to an acute benzodiazepine-withdrawal rather than an intrinsic side effect of the antagonist. In conclusion, Flumazenil proved to be a potent antagonist of benzodiazepines in patients with severe coma and even may serve as a valuable diagnostic in cases of suspected benzodiazepine intoxication. PMID- 2885980 TI - Effects of antipsychotic drugs on cellular immunity in mice. PMID- 2885979 TI - Differential induction profile of drug-metabolizing enzymes after treatment with hypolipidaemic agents. AB - Various hypolipidaemic agents differentially induced microsomal drug-metabolizing enzymes. Clofibrate, clofibric acid, fenofibric acid and dulofibrate, which are mainly hypotriglyceridaemic, increased the content in cytochromes P-450 (77-185% over control), and especially cytochrome P-452-dependent lauric acid 12 hydroxylation (5.6- to 8.4-fold increase). Bilirubin glucuronidation was 2.1- to 2.8-fold stimulated; epoxide hydrolase activity (benzo(a)pyrene-oxide) was only slightly increased by the drugs. By contrast, F1379, which lowers plasma cholesterol only, did not change cytochromes P-450 content and slightly affected the 12-hydroxylation of lauric acid. It dramatically enhanced the epoxide hydrolase activity (7.6-fold), and increased (200%) the glucuronidation of planar group I substrates (4-nitrophenol, 4-methylumbelliferone, 1-naphthol). These effects were accompanied by a highly positive staining of gamma glutamyltransferase in the liver characterized by a great number of intensively coloured foci in the periportal and perilobular area of the tissue. Treatment of rats for three weeks with F1379 did not modify this typical profile in enzyme induction. Such continuous effect could reveal some biochemical changes of hepatocytes with important toxicological relevance. Compared to the parent compound, treatment of rats with two metabolites of F1379 led to a decrease in the induction potency on epoxide hydrolase and on the forms I of UDP glucuronosyltransferase; by contrast, the content in cytochromes P-450 was increased. PMID- 2885981 TI - Proposal for the mechanism of action of urocanase. Inference from the inhibition by 2-methylurocanate. AB - Incubation of urocanase with 2-methylurocanate leads, after an initial normal reaction, to a time dependent inactivation of the enzyme. It is suggested that a tautomeric form of the product, 2-methyl-imidazolone propionate, is the actual inhibitor. On the basis of these and of published experimental data a novel mechanism is proposed for the urocanase reaction. The crucial and initial step is the electrophilic addition of enzyme-bound NAD to the 2-position of the imidazole nucleus of urocanate. PMID- 2885982 TI - Involvement of cell envelope components in the pathogenesis of Vibrio cholerae: targets for cholera vaccine development. AB - Parenteral cholera vaccines have for some years been removed from the WHO recommendations. With a greater understanding of the immunology of gut infections has come the realization that oral vaccines are the most promising approach. There are several possible approaches: killed vaccines, attenuated Vibrio cholerae and true recombinants in which V. cholerae protective antigens are introduced into suitable carrier strains. This latter approach has perhaps greater potential as a carrier strain can be chosen/developed which most effectively stimulates the local immune response in the gut. This necessitates the identification of the important protective antigens. These antigens are thought to be components of the cell envelope which are involved in adhesion and colonization. PMID- 2885983 TI - [1986 SHSTF congress (Swedish Association for Health Care and Nursing Employees)]. PMID- 2885984 TI - [Effect of inflammation on blood protein binding, pharmacokinetics and pharmacodynamics of drugs]. PMID- 2885985 TI - [Clinical studies with salazopyrine--consequences and perspectives]. AB - The efficiency of sulphasalazine (SASP) as a long-acting antirheumatic drug for rheumatoid arthritis is now well established by placebo-controlled studies and comparative trials with injectable gold and D-penicillamin. Early treatment effect and better tolerance suggest the use of SASP especially for early treatment of rheumatoid arthritis. Severe and advanced disease, in which gold and/or D-penicillamin were not effective or toxic, may also be treated with SASP. Open questions are the effect on the radiological progression and the differential indication to antimalarials, oral gold and methotrexat. Positive results of two placebo-controlled studies in ankylosing spondylitis for the first time open the perspective of a long-acting antiphlogistic therapy in this disease. Further open trials observed promising treatment effects of SASP in reactive and juvenile rheumatoid arthritis. Therefore, future clinical studies have to establish indication, benefit-risk-relation and treatment modalities also in these rheumatic disorders. PMID- 2885986 TI - [Sulfasalazine (Azulfidine RA) versus aurothioglucose in therapy of chronic polyarthritis--status report of an open, comparative, multicenter long-term study]. AB - In a current German multicenter comparative study a minimum of 2 X 58 patients with active rheumatoid arthritis (RA) will be treated 36 weeks with sulfasalazine or aurothioglucose. The total time of observation will be 2 years. Up to September 1986 191 patients were recruited in the study, 81 patients divided into two treatment groups were treated for 36 weeks. A preliminary evaluation shows a significant reduction of the parameters of disease activity in both groups. In the sulfasalazine group favourable changes occur earlier than in the gold group. In comparison with gold sulfasalazine shows up to advantage concerning benefit/risk-ratio measured by the rate of side effects causing cessation of therapy and the rate of positive therapeutic response. On the basis of the preliminary data a comparison of grade and duration of ameliorations and of long term tolerance of the two treatment regimens is not possible. PMID- 2885987 TI - [Change in functional capacity and pain intensity of 81 cP patients treated with Azulfidine RA or aurothioglucose. Preliminary statistical assessment of the German multicenter study of the treatment of chronic polyarthritis with Azulfidine RA]. AB - A 36 week treatment with either salazosulfapyridine or aurothioglucose on 81 patients with definite and active rA, most of them from outpatient clinics, did not lead to significant differences in disability and pain intensity. Under both medications 40% were able to reach a statistically significant and clinically relevant improvement, while 25% remained in an unsatisfactory state. PMID- 2885988 TI - [Experiences in long-term therapy of rheumatoid arthritis with sulfasalazine tablets]. AB - To demonstrate the efficacy and compatibility of sulphasalazine as a long term treatment of rheumatoid arthritis, use of the substance (known in Britain as Salazopyrin EN and in Germany as Azulfidine RA) has been compared with that of intramuscular gold. Using very stringent and novel criteria for success--a patient must have no more than one swollen joint after a minimum of 2 years treatment, with less than 30 min of early morning stiffness and still be receiving the drug--the cumulative efficacy of each drug was very similar (32% with sulphasalazine vs 44% with gold). Toxic events leading to drug withdrawal, however, were twice as frequent with gold, and the type of toxic event encountered was considered to be potentially much more serious than those with sulphasalazine (96% of the toxic events on gold fell into the mucocutaneous, renal or haematological groups). PMID- 2885989 TI - [Therapy of seronegative oligoarthritis with salazopyrine]. AB - In an open, controlled study we treated 55 patients suffering of psoriatic arthritis (PsA), 29 patients suffering of Bechterew's disease (MB) and 16 patients with Reiter's syndrome with Salazopyrin at a daily dosage of 2000 mg. We monitored the following criteria of activity: duration of morning stiffness, joint index, global well being scored by the patient and erythrocyte sedimentation rate. All these criteria improved during the treatment; there was a profound improvement in the RS group, whereas the MB group showed only a slight improvement; the PsA group ended between this two extremes. The effect of the drug appeared between week 5 and 15 of treatment. 21% of all patients had to discontinue the treatment because of severe side effects; this figure correlates with the percentages given in the literature. Most of these side effects appeared from week 3 to week 7 of treatment; after week 15 none of the patients had to discontinue the medication of because of severe side effects. PMID- 2885990 TI - [Therapy of juvenile chronic arthritis with sulfasalazine]. AB - Sulfasalazine was used as second line agent in 15 children with different forms of rheumatoid arthritis. In 9 cases amelioration could be achieved with respect to clinical symptoms as well as laboratory parameters. Thus, sulfasalazine can be recommended as basic medication also in juvenile rheumatoid arthritis. PMID- 2885991 TI - [Changes in the blood picture in sulfasalazine therapy of rheumatoid arthritis]. AB - Out of 160 patients with confirmed resp. classical rheumatoid arthritis, according to the ARA criteria, six patients under treatment with sulfasalazine granulocytopenias, in association with thrombocytopenia in one case, and with a decrease in erythrocytes in two cases, have been observed. Remarkably, in all six cases the relatively early hemogram alterations appear as soon as the start of therapy and prompt normalization of blood counts occurs after instant termination of sulfasalazine therapy. Possible mechanisms for the occurrence of these sulfasalazine-induced hematological complications are discussed. These observations, also described by other authors, should be a cause for more frequent blood count tests during sulfasalazine therapy, at least during the first 3 months on a weekly basis. Sulfasalazine represents an asset among the rather limited number of basic therapies available for chronic rheumatoid arthritis. Despite the fact that it is comparatively well tolerated, a close follow-up of the therapy, especially during the initial phases of treatment, is of utmost importance in order to seize upon these reversible hematological disorders at an early stage and thus avoid more serious complications. PMID- 2885992 TI - [Problems of selecting the reagent concentration in the solid-phase immunoenzyme method for determining antibody concentrations]. AB - The problems of selecting the concentration of reagents with the aim of increasing the accuracy and sensitivity of reactions, as well as decreasing the consumption of reagents, are shown as exemplified by the antigen-antibody reaction of the first order. A new approach to the ELISA reaction is proposed, which makes it possible to present the totality of consecutive interactions of the reagents as block diagrams described by known mathematical expressions. The limitations of the linear dependence of the results of the reaction are shown, and the methodological recommendations for overcoming these limitations are given. PMID- 2885993 TI - [Apropos of a symposium on trends in genetics in Brazil held at the 4th meeting of Sao Paulo Geneticists (1985)]. PMID- 2885994 TI - Primary role of glucagon release in the effect of beta-endorphin on glucose homeostasis in normal man. AB - The present study aimed at evaluating the effect of human beta-endorphin on pancreatic hormone levels and on glucose metabolism in normal subjects. Infusion of 143 nmol/h beta-endorphin in 7 subjects caused a significant rise in plasma glucose concentrations (+ 1.7 +/- 0.3 mmol/l) which was preceded by a significant increase in peripheral plasma glucagon levels (+ 44 +/- 13 ng/l). No changes occurred in the plasma concentrations of insulin and catecholamines (adrenaline and noradrenaline). The influence of beta-endorphin per se on glucose homeostasis was studied in 7 other subjects using the euglycaemic clamp technique in which the endocrine pancreatic function was fixed at its basal level with somatostatin together with replacement of basal insulin and glucagon by the exogenous infusion of these hormones. In this new metabolic conditions, beta-endorphin failed to have significant influences on the various parameters of tracer-estimated glucose metabolism (production, utilization, and clearance) and on the plasma levels of the gluconeogenic precursors (glycerol and alanine). Moreover, the levels of pancreatic and counterregulatory hormones (cortisol and catecholamines) were not different between beta-endorphin and control studies. We conclude that the naturally occurring opioid peptide beta-endorphin produced an hyperglycaemic effect in man which appears to be mediated by glucagon. The opioid seems to have no direct effect on glucose metabolism. These results suggest that the metabolic effects of beta-endorphin in normal man are secondary to its impact on pancreatic hormone secretion and not a consequence of a direct modulation of glucose metabolism. PMID- 2885995 TI - The effect of the somatostatin analog SMS 201-995 on normal growth hormone secretion in the rat. A comparison with the effect of bromocriptine on normal prolactin secretion. AB - The somatostatin analog SMS 201-995 was recently shown to be effective in suppressing GH secretion and in causing tumour shrinkage in patients with GH secreting pituitary tumours. In this respect, the action of SMS 201-995 seems similar to that of the dopamine-agonist bromocriptine in patients with PRL secreting pituitary tumours. In the present study we compared the respective effects of SMS 201-995 and bromocriptine on normal rat GH and PRL release in vivo and in vitro. Both in vitro and in vivo, repeated administration of SMS for up till 6 days suppressed circulating GH concentrations, and the ability of the pituitary glands to release GH in vitro. A dose-dependent diminution occurred of the total pituitary GH content in rats treated in vivo with SMS 201-995 for 4-6 days. During short-term in vitro incubation for only 4 h, the total amount of GH measured in the medium + gland was also diminished. Chronic administration with SMS 201-995 (2 micrograms/kg twice daily for 15 days), however, resulted in a complete desensitization of its inhibitory effect on GH synthesis and release. In similar experiments it was shown that the dopamine agonist bromocriptine affects normal PRL secretion in a different manner. Both in vitro (10 nmol/l) and in vivo administration for 6 days (0.2 mg/kg twice daily) greatly inhibited circulating PRL levels and the ability of the pituitary glands to release PRL in vitro. This is, however, in all instances accompanied by an accumulation of PRL within the pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2885996 TI - Cerebrospinal fluid dynorphin1-17 and beta-endorphin in late pregnancy and six months after delivery. No influence of acupuncture treatment. AB - Cerebrospinal fluid (CSF) levels of dynorphin A and beta-endorphin were measured by radioimmunoassay in 62 primiparae in term pregnancy before onset of labour. In 50 of these women acupuncture (AP) treatment was given in an antenatal preparation procedure. In 15 of the AP-treated women, CSF samples were further obtained six months after delivery. Median values for dynorphin A were 7.5 pmol/l in AP-treated women and 6.4 pmol/l in non-treated controls. The puerperal median value for dynorphin A was 7.6 pmol/l. Median values for beta-endorphin were 7.1 pmol/l in AP-treated women and 5.7 pmol/l in non-treated controls. The median beta-endorphin value after delivery was 7.3 pmol/l. There was no significant difference in CSF dynorphin A or beta-endorphin levels between the AP-treated women and non-treated controls in late pregnancy. Consequently, the present study does not support the theory of a positive influence on either the dynorphin or the beta-endorphin system by manual AP. Within subject comparisons of dynorphin-A and beta-endorphin failed to indicate any significant trend in samples obtained in late pregnancy and 6 months after delivery, and there was no increased activity in either the dynorphin or the beta-endorphin system in late pregnancy, as reflected by CSF levels. PMID- 2885997 TI - Tardive dyskinesia with inflated neurons of the cerebellar dentate nucleus. Case reports and morphometric study. AB - Four autopsied cases of tardive dyskinesia manifesting oral hyperkinesia revealed markedly inflated neurons in the cerebellar dentate nucleus (DN), which had not been described previously. The inflation of the neurons was proved to be statistically significant (P less than 0.01) by morphometric study. The nuclei were usually situated in the central portion of the cytoplasm. This inflated change was different from both central chromatolysis and grumose degeneration of the DN, typically observed in progressive supranuclear palsy and dentatorubropallidolysian atrophy, and seemed to be easy to miss without careful observation, since neuronal loss and gliosis were very mild in the DN. Among a few autopsied cases of tardive dyskinesia reported previously, degeneration of the DN was described in only two. It is believed, however, that the inflated neurons of the DN may not be so rare and may be related to the occurrence of some involuntary hyperkinesia, especially oral hyperkinesia following some neurotoxic disorders and/or neuroleptic medications. PMID- 2885998 TI - Early loss of somatostatin neurons in dentate hilus after cerebral ischemia in the rat precedes CA-1 pyramidal cell loss. AB - Somatostatin (SS)- and cholecystokinin (CCK)-immunopositive cell somata in the rat hippocampus were quantitated at day 1, 2, 3 and 4 after cerebral ischemia. A significant (P less than 0.01) 60%-80% loss of hilar and CA-3c SS neurons took place. No CCK neurons were lost. Damage to SS neurons was significant on the second postischemic day and preceded the delayed loss of CA-1 neurons. We speculate that loss of SS neurons, which presumably innervate the inhibitory GABAergic (gamma-aminobutyric acid) interneurons, may induce hyperactivity stimulating the Ca-1 neurons to death. PMID- 2885999 TI - Epidemiological aspects of P-fimbriated Escherichia coli. IV. Extraintestinal E. coli infections before the age of one year and their relation to fecal colonization with P-fimbriated E. coli. AB - In two retrospective studies we have found outbreaks of E. coli pyelonephritis and septicemia to be due to nosocomial spread and fecal colonization with virulent E. coli strains in the neonatal ward of Danderyd Hospital. The incidence of extraintestinal E. coli infections before the age of one year was therefore prospectively studied in all children born at Danderyd Hospital during two and a half years (n = 7963). The number of infections was correlated to the previous fecal colonization with P-fimbriated E. coli. During this study we found no outbreaks of E. coli infections. The incidence of E. coli pyelonephritis before the age of one year was 0.6-0.7%, which we propose to be a baseline incidence. This corresponds well with the low incidence of fecal colonization with P fimbriated E. coli found among these children. Fecal colonization with P fimbriated E. coli during this non-epidemic period had no predictive value for the individual child for the later development of pyelonephritis. PMID- 2886000 TI - Nine months' subcutaneous therapy with synthetic growth hormone releasing factor in children with short stature. AB - The growth promoting potential of GRF(1-29)NH2 was studied in nine boys with short stature over three periods of 3 months. Their short stature was due to partial hGH deficiency/hGH neurosecretory dysfunction and was diagnosed by arginine and insulin stimulation tests and hGH nocturnal profiles. Four patients (Group I) were given GRF, 3-4 micrograms/kg s.c. b.d. during the first period of 3 months, and after an interval of 1 month, the same dose once daily during the second treatment period of 3 months. Five patients (Group II) were given GRF, 3-4 micrograms/kg s.c., once daily during the first and b.d. during the second 3 months of therapy. After a second interval of 1 month without any GRF treatment, the third 3-month period for both groups consisted of one daily injection of GRF, 8-10 micrograms/kg s.c. at 19.00 hours. Total body height and lower leg length were measured by stadiometry and knemometry, respectively. GRF intravenous bolus tests were performed in each patient following fasting, before and at the end of the first and second 3-month periods. Serum IGF-1 and urinary hydroxyproline excretion were determined monthly. Stadiometric growth rate, determined over the whole study period of 11 months including the treatment-free intervals, increased from 4.92 cm/year to 5.97 cm/year (p greater than 0.05). Mean knemometric growth rates increased from 0.28 mm/week before therapy, to 0.35 mm/week during the one injection/day period at low dose, to 0.39 mm/week (p less than 0.05) during the b.d. period, and to 0.40 mm/week during the last 3 months of high-dose GRF given once daily.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886001 TI - Comparative microcytometric analysis of European peripheral T-cell malignant lymphomas (EPTL) and adult T-cell leukemia/lymphomas (ATLL) in Japan. AB - A simultaneous microcytometric analysis of nuclear DNA content and size was performed in 8 European peripheral T cell lymphomas (EPTL) and 8 adult T-cell leukemia/lymphomas (ATLL), comparing their patterns on the nuclear density scattergram (NDS) of DNA content versus nuclear size. The intermingling lymphocytes with or without irregular-shaped nuclei in EPTL and ATLL were interpreted as stimulated reactive. Medium-sized cell-dominated T-zone lymphomas and ATLL pleomorphic medium-sized cell type showed two distribution patterns in the diploid range. The first was oblique zonal cluster (OZC) with the second high concentration in the middle part of it, suggesting mixed proliferation with stimulated reactive lymphocytes, and the second was the high concentration in the lower region of the NDS with some cells corresponding to the growth fraction. In large cell-dominated T-zone lymphomas and ATLL pleomorphic large cell type, the third decreasing pattern in the cell density from the lower part of the OZC to its upper part was found upto the hypertetraploid range. The wide distribution on DNS and giant cells with aneuploid high DNA content were found only in the pleomorphic large cell type and the pleomorphic medium-sized and large cell type of ATLL. The T-immunoblastic type of EPTL showed the third pattern and the pleomorphic large cell type of EPTL, characteristic in the clear cytoplasm, showed the second pattern. PMID- 2886002 TI - [Effects of phencyclidine on levels of dynorphin 1-17 and dynorphin 1-8 immunoreactivities in various brain regions]. PMID- 2886003 TI - [Effects of ohmefentanyl on the content of endorphin in pituitary and brain areas of rats]. PMID- 2886004 TI - [Blocking action of berberine on alpha 2 and alpha 1 adrenoceptors in the rat vas deferens and anococcygeus muscle]. PMID- 2886005 TI - [Blocking effect of puerarin on beta-adrenoceptors of isolated organs and the whole animal]. PMID- 2886006 TI - [Postsynaptic alpha 2 adrenoceptors in coronary artery and its role in sympathetic induced vasoconstriction]. PMID- 2886007 TI - [Effect of beta-adrenoceptor agonists on vascular smooth muscle contraction and transmitter release in the portal vein from spontaneously hypertensive rats]. PMID- 2886008 TI - [Effect of monoamines on ACTH secretion by dispersed perfused cells from the adenohypophysis of barcino chico duck (Anas flavirostris)]. AB - We have pursued with the characterization of ACTH secretagogues from the avian corticomelanotrophic (CM) cell, by testing the ACTH-releasing activity of various monoamines and related drugs, using an in vitro system which uses dispersed perfused duck pituitary cells. The substances used were: noradrenaline (NA), adrenaline (A), dopamine (DA), serotonin (5-HT), phenylephrine (Phe), and isoproterenol (IP). The responses obtained with the substances assayed were compared with those obtained with dilutions of duck median eminence extracts (DME). The order of "intrinsic activities" was: NA = A greater than Phe greater than IP greater than DA = 5-HT. The substances were tested within the range 10( 9)-10(-4) M. All substances tested behaved as partial agonists with respect to DME. The "intrinsic activity" (Vmax) of the most potent agonists tested, A and NA, was 0.66 of that obtained with DME. It is concluded that in the duck, the CM cells secrete ACTH in response to A and NA (and other pharmacological substances) at doses which are compatible with a physiological role of those catecholamines acting directly upon the CM cell of the avian adenohypophysis. 5-HT and DA behaved as very weak agonists in stimulating ACTH release from duck CM cells in the system employed. PMID- 2886009 TI - Effects of adrenoceptor antagonists on vagally induced gastric and duodenal HCO3- secretions in the cat. AB - Experiments were performed on chloralosed cats with ligated adrenal glands. The cervical vagi were cut and arranged for electric stimulation. The gastric lumen was continuously perfused, and the secretions of H+ and HCO3- were calculated from pH/pCO2 measurements in the perfusate. Gastric motility was recorded as changes in hydrostatic pressure within the perfusion system. Mucosal HCO3- secretion into a duodenal segment, distal to the papilla of Vater and Brunners gland area, was titrated in situ by a pH-stat equipment. Animals pretreated with various adrenoceptor blockers or splanchnicotomy were compared with control animals with intact sympatho-adrenergic system. Basal gastric motor activity, H+ and HCO3- secretions, as well as duodenal HCO3- secretion were not influenced by prazosin, propranolol or splanchnicotomy. Yohimbine increased significantly basal gastric HCO3- secretion, but did not influence basal gastric motor activity, H+ secretion or duodenal HCO3- secretion. Vagal stimulation in yohimbine-treated or splanchnicotomized animals induced significantly larger gastric contractions, HCO3- secretory and duodenal HCO3- secretory responses than in the controls, whereas these responses to vagal stimulation were small in prazosin- or propranolol-treated animals. Vagally induced gastric H+ secretory responses were significantly larger in propranolol-treated animals than in controls, whereas prazosin-treated, yohimbine-treated or splanchnicotomized animals in this regard did not differ from the controls. The results suggest the existence of a sympathetic, probably alpha-2-adrenergic, inhibition of vagally induced gastric contractions as well as of the gastric and duodenal HCO3- secretions. PMID- 2886010 TI - Antrum participates in the postprandial augmentation of the acid response to exogenous gastrin in conscious cats. AB - A humoral mechanism, potentiating the maximal acid, but not the pepsin response to exogenous gastrin in cats, is activated by protein-rich food in the stomach or duodenum, but not in the jejunum. In the present study, the effect of an oral meat meal on the maximal acid response to pentagastrin was investigated in Heidenhain pouch (HP) cats, and in antrectomized HP cats with duodenal exclusion and gastrojejunostomy Rouxen-Y. Antrectomy and duodenal exclusion abolished the postprandial HP acid response, and feeding did not potentiate the acid response to pentagastrin. The finding suggests that the gastrin-potentiating mechanism in the stomach is localized in the antrum, and it cannot be demonstrated in the jejunum. The basal plasma levels of gastrin and somatostatin did not differ in antrectomized and non-antrectomized cats. Antrectomy and duodenal exclusion abolished the postprandial gastrin and somatostatin responses. The plasma somatostatin increase during pentagastrin infusion persisted after antrectomy and duodenal exclusion. It is concluded that the antrum is not mandatory for the basal plasma levels of gastrin and somatostatin, but the postprandial gastrin response is of antral origin and may release somatostatin. Pentagastrin infusion releases extra-antral somatostatin in cats. PMID- 2886011 TI - Influence of sodium deoxycholate on morphology, net fluid transport and motility in the small intestine of the rat. AB - Intestinal fluid secretion and motility were induced by luminal perfusion of rat small intestine with sodium deoxycholate, a dihydroxy bile salt for 1-3 h. Changes in intestinal morphology were studied simultaneously with the changes in fluid transport and motility. The results suggest that the bile salt causes epithelial lesions which may lead to a reduced fluid absorption in the villi, thereby explaining part of the total change in net fluid transport caused by the bile salt. Pyrilamine and indomethacin did not influence the bile salt-induced secretion. Based on earlier studies, it is proposed that the major part of the bile salt-evoked secretion is mediated via activation of intramural nervous reflex(es), which also stimulate the intestinal smooth muscle cells. PMID- 2886012 TI - Verapamil in treatment of severe schizophrenia. PMID- 2886013 TI - Role of transglutaminase in proinsulin conversion and insulin release. PMID- 2886014 TI - Central stimulant abuse: neurochemistry and pharmacotherapy. AB - This paper reviews certain clinical and neurochemical aspects of cocaine abuse. Once entrenched patterns of addiction have developed, cocaine addicts suffer progressive financial, medical, psychiatric and psychosocial deterioration that results, to some extent, from cocaine-induced neurochemical alterations in the brain. While cocaine produces euphoria through its stimulatory effect on dopamine neurons, several lines of evidence suggest that dopamine depletion occurs after chronic cocaine abuse. The dopamine neurotransmitter system is therefore a natural starting point for understanding the biology of cocaine addiction and selecting suitable adjunctive pharmacological agents. Furthermore, the dopamine depletion hypothesis implies that cocaine is "physically" addictive and provides a biological framework for understanding this disease and refining present therapeutic approaches. PMID- 2886015 TI - Uses of gamma-glutamyltransferase in experimental toxicology. PMID- 2886016 TI - The conservative treatment of the fractures and dislocations of the extremities in children. AB - Both authors have dedicated most of their time since 1948 to the treatment of fractures in children. On the basis of their experience they are therefore submitting to the medical public those methods and results of the conservative treatment of fractures and dislocations in children which stood the test of time. The experiences of both authors as well as successful therapeutic methods of other surgeons are discussed in this book. Differences are stated between fractures in adults and in children which may be attributed to the growth factor of children's bones and their enormous biological drive. These factors will play their part in correcting certain displaced fractures by re-moulding, fractures which in an adult would have to be perfectly reduced unless a permanent deformity should ensue associated with subsequent impairment of function to the injured limb. The authors are stating which displaced angulations and side to side displacements in a fracture may be left and which must be repaired under all circumstances and why, if conservative treatment fails, surgery has to be performed. Sideways and longitudinally displaced fractures, especially metaphysial ones do not warrant a perfect reduction. Rotational displacements must be corrected every time even in very small infants e.g. in newborn babies. Age plays an important part in the healing of fractures. Moulding and union of a fracture will be most rapid in newborn babies and infants while in fractures of adolescents a similar procedure has to be adopted as in fractures of adults. Special problems of epiphysiolyses and epiphysial fractures are discussed emphasizing that conservative treatment may be unsuccessful in epiphysiolyses Salter-Harris type III and IV and surgical intervention may be indicated. Fractures of upper and lower limbs are dealt with in detail while paying special attention to obstetrical fractures. Fractures round the elbow are treated in a similar manner, they will frequently heal in angulation of the upper limb and may cause nerve injuries and ischaemic changes of the forearm. Special attention is being paid to the longitudinal overgrowth of fractures of the femoral diaphysis associated with the sequelae of the treatment of these very serious injuries to newborn babies and infants as well as to toddlers and older children. PMID- 2886018 TI - Haemagglutinating and hydrophobic properties of Corynebacterium (Eubacterium) suis. PMID- 2886017 TI - Blood vessel ontogeny in upper extremity of man as related to developing muscles. AB - Vascular bed and its relationship to differentiating muscular tissue was studied in a set of 104 upper limbs of human embryos and foetuses, gradually increasing from 10 to 120 mm C-R length. Knowledge obtained on the ontogeny of vascular bed was supplemented by findings in 75 limbs of adults treated by preparation technique. Embryonic and foetal material was treated histochemically a--to demonstrate vascular bed reaction for alkaline phosphatase (AP), ATPase, and dipeptidylpeptidase IV (DPP IV), b--to study differentiating muscular tissue for enzyme--ATPase and tetrazoliumreductase (NaDH2, c--to distinguish muscular tissue elements with toluidine blue staining for degree of maturity. Observations concerned several items, namely a--the ontogeny of main arterial trunks in the forearm and hand, b--muscle fibre type differentiation in antebrachial muscular primordia, c--formation of vascular bed as related to differentiating muscular tissue in the forearm and hand. Therefore our results are grouped as follows: ad a--Arterial trunks differentiate along with other limb structures in 12-18 mm C-R length embryos. Thus in embryos above 18 mm C-R length antebrachial and hand trunks are fully formed. Vascular trunks differentiate from deep vascular network via gradual reduction and magistralization in conformity with the general laws of haemodynamics. All arterial trunks forming in the limb during the ontogeny branch off the original axial artery in regio cubiti. In a. radialis trunk it has been ascertained that this blood vessel does not originate from a. brachialis superficialis, as generally reported, but its formation conforms to the same general principles as blood vessel trunks. So it branches off the original axial artery, as other trunks do. A. mediana formed during vascular trunks differentiation later in the ontogeny does not obliterate but changes into the constant a. comitans n. mediani. ad b--First involved in differentiation in antebrachial muscular primordia are the "fast" type fibres (according to Peter et al., 1972) (fast glycolytic-FG-type fibres followed by fast oxidative glycolytic FOG-type fibres) in 27-30 mm C-R length embryos. "Slow" type fibres (slow oxidative-SO-type fibres) may not be demonstrated histochemically in antebrachial muscles earlier than 45 mm C-R length foetuses. The maturity of muscular elements may be demonstrated by staining with toluidine blue on cytoplasm basophilia of cells. Sarcolytic myotubes in muscular primordia histochemically display typical features which distinguish them markedly from other differentiating muscle fibres.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2886019 TI - Liposome encapsulated subunit (VP1) and virion vaccines against foot-and-mouth disease. AB - Subunit vaccine prepared from VP1 protein of foot-and-mouth disease virus (FMDV) types 0 and Asia 1 protected guinea pigs against FMD and also induced high levels of antibody. Liposomes have been used as a safe and potent immunological adjuvant for FMD vaccines. Vaccines prepared from inactivated virus types 0 and Asia 1 encapsulated in liposomes protected guinea pigs against challenge with homologous virus and showed good antibody response in pigs on a small scale field trial. PMID- 2886020 TI - Hepatitis B surface antigen/IgM complexes: relation to receptors for polymerized human serum albumin, hepatitis B virus (HBV) DNA polymerase activity and HBV markers. AB - The presence and the level of hepatitis B surface antigen (HBsAg)/IgM complexes were determined in 54 chronic HBsAg carriers in relation to receptors for polymerized human serum albumin (pHSA-R) tested by specific radioimmunoassay, and to hepatitis B virus-DNA polymerase (HBV-DNAp). HBsAg/IgM complexes, correlated significantly with the HBsAg concentration but, at a similar HBsAg concentration, significant highest values of HBsAg/IgM complexes were found among HBeAg positive patients. In addition, a significant correlation was found between HBsAg/IgM complex levels, HBeAg titres and HBV-DNAp activity (r = 0.628, p less than 0.001 and r = 0.559, p less than 0.001, respectively). Moreover, a positive linear correlation was found when comparing HBsAg/IgM complexes and pHSA-R levels (r = 0.848, p less than 0.001). Patients who were positive for HBsAg/IgM complexes had a significantly higher glutamate-pyruvate transaminase (GPT) level than those who did not show any complexes. In conclusion, HBsAg/IgM complexes seemed to be indirectly related to HBV replication. PMID- 2886021 TI - Rapid method for the detection of synergism in combinations of antiviral substances. AB - The plaque inhibition method was modified in order to evaluate the effectiveness of various combinations of antiviral substances. One substance (A) diffuses from the centre of cell culture, the other (B) is incorporated into the agar overlay at subinhibitory concentration. The inhibitory effect of the combination (A + B) is demonstrated by the increase in size of the inhibitory zone in comparison with the control inhibitory zone produced by the substance A alone. The ratio of the diameter of the inhibitory zone with substance combination (A + B) to the diameter of single drug control zone (substance A) serves as index DI (degree of interaction). Quantitative evaluation of the degree of potentiation using isobolograms showed that DI greater than 1.5 indicate a synergistic effect of the respective combinations. This inexpensive method can serve for rapid selection of suitable combinations out of number of substances. Model experiments were performed with combinations of selected inhibitors of virus replication. PMID- 2886022 TI - Serological relationship among ten strains of avian infectious bronchitis virus. AB - Ten strains of avian infectious bronchitis virus (IBV) were studied serologically by cross-neutralization test using rabbit and chicken immune sera. With the chicken sera all 10 IBV strains were antigenically related. In particular, anti KH serum neutralized all heterologous strains except of the Ishida strain; Nerima strain was neutralized by all antisera except of anti-Ishida serum. Most cross reactions were less or more heterologous, thus all 10 IBV strains seemed to belong to one serological type. Using rabbit sera, all strains except of Connecticut A-5968, cross-reacted with certain other strains. Most cross reactions were partially heterologous showing one-way-relationship; heterologous relations were observed less frequently than with chicken sera. PMID- 2886023 TI - Differentiation between two African arenaviruses (Lassa and Mozambique) by plaque assay. AB - The biological characteristics of Lassa and Mozambique viruses were compared by plaque assay. Both viruses produced plaques under the same conditions, however, Lassa virus plaques measured on average 2 mm in diameter being twice as large as the Mozambique virus plaques. By plaque reduction tests, cross protection was demonstrated between both viruses showing that Lassa and Mozambique viruses are distinct but related. PMID- 2886024 TI - Antigenic variation of the viruses belonging to the tick-borne encephalitis complex as revealed by human convalescent serum and monoclonal antibodies. AB - Solid-phase enzyme-linked immunoassay (ELISA) was used for the detection of antigenic relationships and/or differences among the viruses belonging to the tick-borne encephalitis (TBE) complex. Monoclonal antibodies of IgM class with haemagglutination-inhibiting activity to the Skalica strain of TBE virus were used to compare the TBE complex viruses. Antigenic analysis of 9 viruses of the TBE complex, isolated from Eurasia and America showed close relationships among them. Nevertheless, it was possible to differentiate the Skalica strain from Langat, louping-ill and Omsk haemorrhagic fever (OHF) viruses by ELISA when monoclonal antibodies and antigens were diluted 1:10,000. Monoclonal antibodies to the Russian spring-summer encephalitis virus did not react with the Skalica strain in immunofluorescence test. By the use of convalescent serum no reaction was found with louping-ill, Russian spring-summer encephalitis, Powassan and OHF viruses in haemagglutination-inhibition (HI) test. PMID- 2886025 TI - Antigenicity of chloroform-methanol-treated Coxiella burnetii preparations. AB - Phase I Coxiella burnetii (C.b.) cells untreated (Cb I) or treated with chloroform-methanol (CM) mixture (Cb I-CM) were compared as to their capacity to induce antibodies in laboratory animals and cattle, their ability to elicit delayed type hypersensitivity (DTH) reaction in mice and rabbits and protective effect in mice. In all animal species (mice, guinea pigs, rabbits, cattle) tested, the same doses of Cb I-CM cells induced lower levels of both phase I and phase II microagglutinating (MA) antibodies than Cb I cells at different intervals post-immunization (p.i.). Though for elicitation of DTH reaction in rabbits immunized with different C.b. preparations lower doses of Cb I than of Cb I-C M cells were necessary, C.b. cells caused inflammatory reaction at lower doses also in control rabbits. In mice immunized with Cb I and Cb I-CM cells, but not with trichloracetic acid extract (TCAE) from intact Cb I cells, DTH reaction was elicited by the same doses of Cb I and Cb I-CM cells. Higher immunizing doses of Cb I-CM than of Cb I cells were required, however, to induce DTH reaction (as tested by TCAE) as well as protection to phase I virulent challenge. TCAE from intact Cb I cells was protective in mice also at lower doses than TCAE from Cb I CM cells (TCAE-CM). In humans who suffered from Q fever one year ago, higher proportion of positive skin test (ST) reactions and antibody recalls with higher mean geometric titres (MGT) of phase II MA antibodies was noticed following intradermal administration of TCAE than of TCAE-CM. When humans with no evidence of Q fever in past were vaccinated with TCAE or TCAE-CM, the former preparation not only caused higher proportion of both local and general post-vaccination reactions, but also of phase II MA antibody response and positive ST reactions as tested by TCAE 3 months post-vaccination in addition to higher proportion of phase II MA antibody recalls. PMID- 2886026 TI - Studies of the major DNA binding proteins of two bovine herpes mammillitis virus isolates. AB - Antigenic cross-reaction of the DNA-binding protein between herpes simplex virus type 2 (HSV-2) and two bovine herpes mammillitis virus (BHMV) isolates (BHM-1 and BHMV CSIRO 290) was demonstrated by indirect immunofluorescence. Southern blot analysis showed a region of homology between HSV-2 BglII O DNA (coding for the HSV-2 major DNA-binding protein) and BHMV XbaI DNA fragment N, suggesting a similar gene map unit position on both genomes. PMID- 2886027 TI - Identification of continuous green monkey spleen cell line 455. AB - Green monkey spleen continuous cell line 455 has been identified by karyologic analysis, by isoenzyme characteristics and electron microscopy. It has been shown that the line 455 consists of green monkey cells; it is not contaminated by other cells from the green monkey, or by other animal or human cells. PMID- 2886028 TI - Fusion of erythrocytes by Newcastle disease virus. AB - Newcastle disease virus-induced fusion of chick embryo (CE) and chicken erythrocytes has been studied at the ph range between 5.5 and 8.0. The highest degree of fusion of CE erythrocytes was observed at pH 5.5, whereas the chicken erythrocytes fused at pH 5.5-6.0 only. Freezing and thawing of low-haemolytic virus preparation increased its erythrocyte fusion activity. Ammonium chloride did not cause a statistically significant effect on the multiplication of virus preparations expressing different haemolysis and erythrocyte fusion activity. PMID- 2886029 TI - Partial characterization of a Hantavirus isolated from a Clethrionomys glareolus captured in Belgium. AB - A Hantavirus was isolated in Vero-E6 cells from lungs of a free living bank vole (Clethrionomys glareolus) captured in Turnhout, Province of Antwerp--Northern part of Belgium. With help of monoclonal antibodies the Belgian Hantavirus isolate could be clearly differentiated from Hantaan virus strain 76-118, Prospect Hill virus strain PH1 and SR11, a Hantavirus isolated from laboratory Wistar rat in Japan, but not from the nephropathia epidemica virus strain Hallnas. PMID- 2886030 TI - Loss of infectivity of red clover mottle virus by lysolecithin. AB - 2-0-hexadecyl-glycero-3-phosphocholine (GPC) 1 mmol/l solution reduced the infectivity of red clover mottle virus (RCMV) by over 90%. The binding of GPC molecules to RCMV particles was investigated with 1H-nmr spectroscopy, which showed a striking interaction between virus particles and GPC molecules. In 10 mmol/l GPC solution each virus particle bound about 10(3) GPC molecules. PMID- 2886031 TI - Study of avian adenovirus DNA infectivity in chick embryos. AB - Inoculation of CELO adenovirus deproteinized DNA into the allantoic cavity of 9 day-old chick embryos (CE) induced the synthesis of infectious viral particles. The produced virions appeared to be identical with CELO adenovirions in terms of morphology, electrophoretic and immunochemical properties of hexon major capsid protein and also of DNA dot-hybridization. High infectivity of CELO DNA (minimal infective dose equaled 40 ng) may be also related, at least in part, to the absence of deoxyribonuclease activity in the allantoic fluid (AF). PMID- 2886032 TI - ELISA for total IgE and IgG detection in rat serum. Changes with immunization or adjuvants. AB - Total IgE and IgG serum levels were measured in rats treated with egg albumin (EA), Bordetella pertussis (Bp) and aluminium hydroxide gel (alum), and in rats administered with Bordetella pertussis or alum alone. Two ELISA micromethods have been developed to measure IgE and IgG changes. Immunoglobulin serum levels were evaluated 14 days after immunization. The highest IgE levels were obtained after sensitization with EA suspended in alum s.c. and administered with Bp i.p. The IgE production induced by Bp alone was significantly lower than that of the former. The IgE concentrations from alum treated group were the same as those obtained in the untreated animals. IgG serum levels remained unchanged in the different immunization procedures assayed. PMID- 2886033 TI - Outpatient management of coronary artery disease. PMID- 2886034 TI - Antianginal drug therapy for silent myocardial ischemia. PMID- 2886035 TI - Observations on increased susceptibility to coronary artery vasospasm during beta blockade. PMID- 2886036 TI - The 1980s: a patient-specific therapeutic approach in hypertension. AB - The conventional "stepped-care" approach to the treatment of hypertension deserves revision. Rational therapy considers a variety of factors to obtain maximum efficacy, safety, tolerability, compliance, and neutralization of neural tone for the prevention of sudden death. The patient's age, gender, race, behavior profile, hemodynamic and neurohumoral status (plasma renin activity, norepinephrine/epinephrine ratio), and quality of life will help determine the choice of antihypertensive agent. Concomitant risk factors (smoking, obesity, diabetes, hypercholesterolemia), the presence of sequelae (left ventricular hypertrophy and/or failure, renal failure), and the existence of other disorders (mitral valve prolapse, depression, anxiety) must also be considered when initiating treatment. In addition, the cost of ancillary expenses (laboratory tests, hospitalizations, and emergency room visits) must be weighed against the potential benefits of therapy. Beta blockers are effective, well tolerated, and versatile for the treatment of concomitant cardiovascular disorders and as behavior modifiers. Calcium channel blockers and angiotensin converting enzyme inhibitors also show promise and merit consideration as therapy for specific groups of hypertensive patients. PMID- 2886037 TI - Quality of life after myocardial infarction. AB - The long-term physical and psychologic well-being of patients who have sustained a myocardial infarction is dependent on skilled care during the first hours. Although the immediate preservation of life is the first priority, the relief of symptoms and anxiety and the protection of the myocardium are of short- and long term importance not only to the quantity but also to the quality of life. Pain relief, particularly in the prehospital phase, is often inadequate. Fear, triggered by pain, may be aggravated by the environment; aggressive (and often unnecessary) measures and the inhuman use of technology may interfere with personal care. Intensive observation is essential for the control of dangerous arrhythmias; the early use of fibrinolytic agents and beta blockers limits the extent of myocardial damage and reduces mortality. The effectiveness of therapy for cardiac failure and shock is questionable. The value of invasive monitoring and of inotropic drugs is uncertain, although the relief of symptoms by diuretic agents and vasodilator drugs is not in doubt. Success in the management of myocardial infarction depends on a highly individualized approach. PMID- 2886038 TI - Use of beta blockers in postinfarct prophylaxis: aspects on quality of life. AB - The value of beta blockade after myocardial infarction is extremely well documented. Close to 50 randomized trials have been performed, involving about 40,000 patients with short- or long-term follow-up. Over 20,000 patients have been included in more than 20 placebo-controlled trials with a follow-up period of 3 months or more. In long-term follow-up studies, about 1 to 2 weeks to 1 year after myocardial infarction, mortality was reduced by 21% and reinfarction by 24% (about 20,000 patients in 24 trials). The trial medication was withdrawn in about 20% in both placebo and beta-blocker groups in the major trials. In addition to reduction of mortality and reinfarction rate, benefits have clearly been demonstrated on severity of chest pain, arrhythmias, and other thromboatherosclerotic complications, as well as on readmissions. Significantly more patients experienced congestive heart failure, hypotension, bradycardia, and cold hands with beta-blocker treatment, whereas no clear-cut difference was found for atrioventricular block, bronchial constriction, and intermittent claudication. Some studies have reported more tiredness, depression, and gastrointestinal disturbances. In the Stockholm metoprolol trial, analyses on quality of life have been performed. In this trial, 3 years of metoprolol treatment after myocardial infarction resulted in a prolongation of both survival and time spent completely asymptomatic, as well as in an optimal functional state. Furthermore, less time was spent disabled after serious atherosclerotic complications. Long-term beta blockade after myocardial infarction reduces mortality and morbidity but causes adverse reactions in some patients. With proper selection of patients and type and dosage of beta blocker, survival without atherosclerotic complications and side effects can be prolonged. PMID- 2886039 TI - Ischemic heart disease: a patient-specific therapeutic approach with emphasis on quality of life considerations. AB - Advantages and disadvantages of the various therapies for stable angina are considered with particular attention to quality of life. Advantages of coronary artery bypass surgery (CABS), apart from the question of survival, include less angina, less activity limitation, and less need for drugs than with medical treatment. However, data from the Coronary Artery Surgery Study (CASS) and others show that there is no difference between medical and surgical therapy in return to work and in need for subsequent hospitalization. In CABS patients, there is also predictable return of angina, substantial late vein graft occlusion, and possibly increased progression of native coronary artery disease in grafted vessels. Percutaneous transluminal coronary angioplasty (PTCA) has advantages similar to those of CABS, with very low initial mortality and major complication rates, minimal discomfort, very short disability period, and moderate cost. Its major disadvantages are a high short-term reocclusion rate and uncertain long term outcome. Beta blockers provide good control of angina, have additional antihypertensive and antiarrhythmic effects, and may be beneficial in preventing sudden cardiac (arrhythmic) death and limiting myocardial infarct size, should these events supervene in the patient with angina. Disadvantages of beta blockers involve the occasional major side effects, including potential exacerbation of bronchospasm, peripheral vascular disease (PVD), diabetes, congestive heart failure and bradyarrhythmia, and frequent "nuisance" side effects. Calcium blockers control both exercise and rest angina and pose no problem in patients with bronchoconstriction, PVD, or diabetes. Disadvantages include need for frequent dosage, cost, and side effects. Long-acting nitrates have few major side effects and usually transient minor side effects, with little effect on quality of life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886041 TI - Comparison of morphologic changes and luminal sizes of saphenous vein and internal mammary artery after simultaneous implantation for coronary arterial bypass grafting. PMID- 2886040 TI - Color Doppler echocardiographic assessment of the change in the mitral regurgitant volume. AB - We studied the possibility that a mitral regurgitant Doppler signal area on a two dimensional color Doppler echocardiogram can reflect changes in mitral regurgitant volume in 24 patients with several types of mitral regurgitation. In 20 patients, mitral regurgitant Doppler signal areas were clear enough to measure. Injections of phenylephrine were given to these patients during the recording of the mitral regurgitant Doppler signal area in the same views and with the same Doppler gains. The mitral regurgitant Doppler signal area, blood pressure, and heart rate were measured before and after phenylephrine provocation. In addition, inhalation of amyl nitrite was performed during the recording of the mitral regurgitant Doppler signal area in the same way. Injection of phenylephrine resulted in an increase in the mitral regurgitant Doppler signal area accompanied by an increase in blood pressure and a decrease in heart rate. On the other hand, inhalation of amyl nitrite resulted in a decrease in the mitral regurgitant Doppler signal area, a decrease in blood pressure, and an increase in heart rate. A positive correlation between the change in blood pressure and that in the mitral regurgitant Doppler signal area was observed. In conclusion, two-dimensional color Doppler echocardiography may be useful in the assessment of the acute change in regurgitant volume in the patient with mitral regurgitation. PMID- 2886042 TI - Usefulness of low-level exercise testing early after acute myocardial infarction in patients taking beta-blocking agents. AB - The value of low-level exercise testing early after acute myocardial infarction (AMI) in 207 patients taking beta-blocking drugs was evaluated in a multicenter study of prognosis after AMI. After stratifying patients according to the absence of significant rales upon admission or pulmonary congestion on the admitting chest x-ray, the results of the exercise test (ability to complete the 9-minute protocol) permitted a large cohort (108 patients, 52% of exercising patients) with no deaths from cardiac causes in the year after AMI to be identified. The results suggest that even in patients taking beta-blocking agents, low-level exercise testing together with clinical stratification has value in identifying a large group of patients with a good prognosis after AMI. PMID- 2886043 TI - The relationship of secretin and somatostatin levels in plasma to glucose administration and acid secretion during fasting. AB - The concentrations of secretin and somatostatin in plasma were measured in 10 healthy subjects during a 4-day fast. The fast induced increased concentrations of plasma secretin (from 1.2 +/- 0.5 to 9.5 +/- 2.3 pmol/l) and somatostatin (from 5.2 +/- 1.5 to 8.6 +/- 1.7 pmol/l). Gastric aspiration for 1 h suppressed the high concentrations of secretin by 46% and somatostatin by 27%. The intravenous infusion of glucose reduced the plasma secretin even further by 88%; the decrease in somatostatin was not statistically significant. The study shows that gastric aspiration and/or glucose infusion suppressed the high plasma concentration of secretin and that factors other than hyperchlorhydria must be involved in the hypersecretinemia seen during starvation. The elevated plasma somatostatin concentration seen during starvation may be a consequence of increased acid secretion. PMID- 2886044 TI - Multiple endocrine neoplasia, type 1, with pancreatic cholera. AB - A 20-yr-old black woman presented in 1969 with headache, amenorrhea, hyperprolactinemia, hypogonadotropism, hypogonadism, and hypercalcemia due to a chromophobe adenoma. She received 5000 rads to the sella. One year later she was found to have hyperparathyroidism due to parathyroid adenoma and three and a half glands were removed. Thirteen years later she presented with 3 months of profuse watery diarrhea, hypokalemia, hypercalcemia, hyperchloremic metabolic acidosis, and a normal anion gap. A vasoactive intestinal polypeptide-producing tumor of the pancreas was found and successfully removed, after which hypercalcemia resolved. This is an unusual case of the multiple endocrine neoplasia syndrome, type 1, being associated with a vasoactive intestinal polypeptide-oma and pancreatic cholera. PMID- 2886045 TI - The glomerular and tubular actions of angiotensin II. AB - Evidence has accumulated that angiotensin II (AII) exerts multiple influences upon renal function through effects on vascular, glomerular, and tubular structures. Infusion of AII alters glomerular ultrafiltration by decreasing nephron plasma flow, increasing glomerular capillary hydrostatic pressure (PG) and the hydrostatic pressure gradient (delta P) due to increases in both afferent and efferent arteriolar vascular resistance, and effecting a reduction in the glomerular ultrafiltration coefficient (LpA), the product of glomerular membrane hydraulic conductivity and effective surface area for ultrafiltration. Spontaneous increases in intrarenal AII generation, such as observed in chronic NaCl depletion, also produce reductions in nephron plasma flow, increases in delta P, and major reductions in LpA. Angiotensin-converting enzyme inhibitor and saralasin administration prevent these alterations in plasma flow, delta P, and LpA. These AII-induced alterations in LpA may be mediated by AII effects upon the glomerular mesangial cell since AII receptors are expressed and this cell contracts in vitro in the presence of AII. Multiple studies have shown a positive effect of AII (approximately 10(-11) mol/L) on proximal tubular reabsorption, an effect independent of AII effects on peritubular physical factors. These AII effects upon the proximal tubule are clearly independent of interaction with adrenergic influences. AII also influences other mesangial cell functions such as uptake of macromolecules from the circulation. AII also exerts effects by influencing the functional expression of renal adrenergic activity, as demonstrated by studies with renal nerve stimulation in the presence and absence of angiotensin-converting enzyme inhibitor and saralasin. Inhibition of AII activity also clearly suppresses tubuloglomerular activity and the PG response to alterations in distal tubular flow rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886046 TI - Special uses for captopril. AB - Plasma renin activity (PRA) is markedly increased by captopril. There is not enough separation between the changes in PRA of patients with renal artery stenosis (RAS) to separate them reliably from those with essential hypertension. A minimal response may suggest primary aldosteronism. Captopril does increase the ratio of PRA in the venous blood from a kidney with RAS to that of the contralateral kidney. Captopril, 25 to 50 mg orally, given before renal vein PRA sampling will increase the sensitivity and specificity of the test. Treatment with current antihypertensive drugs need not be discontinued. Scleroderma renal crisis (SRC) used to be uniformly lethal within a few months. Modern, aggressive antihypertensive therapy has made survival of 2 or more years common. Not all patients respond, and some progress to renal failure despite good BP control. Captopril has been used with success in some patients with idiopathic edema. In conclusion, captopril markedly enhances the accuracy of renal vein renin assay for the diagnosis of RAS and is of major value in the treatment of SRC. PMID- 2886048 TI - Linkage and genetic counselling for the fragile X using DNA probes 52A, F9, DX13, and ST14. AB - Linkage data using the markers DXS51, F9, DXS15, and DXS52 are presented from 14 pedigrees segregating with the fragile X. Cytogenetic and DNA data were combined by two- or three-point linkage analysis for estimation of lod scores and carrier probabilities in potential carriers. Recombination frequencies (theta) corresponding to maximum z scores (zeta) were obtained for DXS51 (zeta = 3.45, theta = 0.0), DXS15 (zeta = 0.40, theta = 0.06), F9 (zeta = 3.15, theta = 0.09), and DXS52 (zeta = 3.60, theta = 0.11) with the fragile X. Considerable alterations to carrier probabilities occurred in some cases, especially when flanking markers were informative. The chance of mentally impaired offspring was reduced to 1% for five of eight women with prior carrier probabilities of 32%. Three pedigrees were identified in which mutation had possibly occurred. An alternative explanation for two of these was inheritance of the fragile X from normal males and for the other inheritance from a clinically normal woman. Probabilities were computed for each of these alternatives. PMID- 2886047 TI - Human homeo box-containing genes located at chromosome regions 2q31----2q37 and 12q12----12q13. AB - Four human homeo box-containing cDNAs isolated from mRNA of an SV40-transformed human fibroblast cell line have been regionally localized on the human gene map. One cDNA clone, c10, was found to be nearly identical to the previously mapped Hox-2.1 gene at 17q21. A second cDNA clone, c1, which is 87% homologous to Hox 2.2 at the nucleotide level but is distinct from Hox-2.1 and Hox-2.2, also maps to this region of human chromosome 17 and is probably another member of the Hox-2 cluster of homeo box-containing genes. The third cDNA clone, c8, in which the homeo box is approximately 84% homologous to the mouse Hox-1.1 homeo box region on mouse chromosome 6, maps to chromosome region 12q12----12q13, a region that is involved in chromosome abnormalities in human seminomas and teratomas. The fourth cDNA clone, c13, whose homeo box is approximately 73% homologous to the Hox-2.2 homeo box sequence, is located at chromosome region 2q31----q37. The human homeo box-containing cluster of genes at chromosome region 17q21 is the human cognate of the mouse homeo box-containing gene cluster on mouse chromosome 11. Other mouse homeo box-containing genes of the Antennapedia class (class I) map to mouse chromosomes 6 (Hox-1, proximal to the IgK locus) and 15 (Hox-3). A mouse gene, En 1, with an engrailed-like homeo box (class II) and flanking region maps to mouse chromosome 1 (near the dominant hemimelia gene). Neither of the class I homeo box containing genes--c8 and c13--maps to a region of obvious homology to chromosomal positions of the presently known mouse homeo box-containing genes. PMID- 2886049 TI - Fc-receptor function of the mononuclear phagocyte system in glomerulonephritis secondary to some multisystem diseases. AB - The Fc-receptor function of the mononuclear phagocyte system was examined in 30 patients affected by multisystem diseases with glomerular involvement by measuring the immune clearance of IgG-sensitized autologous red blood cells in vivo and the immune phagocytosis of monocytes in vitro. Patients studied in the phase of clinically active renal disease showed a significantly reduced Fc receptor function by both in vivo (p less than 0.001) and in vitro (p = 0.003) assays, as compared to those studied during an inactive phase. Though the nature of the defect remains uncertain, it appears to be related to the active phase of the renal disease as also confirmed by the analysis of individual cases studied longitudinally. PMID- 2886052 TI - Spare receptors, partial agonists, and ternary complex model of drug action. AB - The occurrence of spare receptors and partial agonists for smooth muscle contractions mediated by alpha 1-adrenergic receptors can be accounted for with a ternary complex model of drug action presented here. In this model, receptor ligand complexes are assumed to be inactive until the complex binds to an activating protein. Contractile responses are assumed to be proportional to the concentration of ternary complex (receptor-ligand-activator) regardless of the ligand involved. Antagonists are unable to form the ternary complex. Spare receptors are present as the inactive receptor-ligand complex. Such a model is shown to fit already published data on membrane binding of alpha 1-adrenergic agonists as well as contractile responses to the agonist. Schild plots are expected to resemble those of a single-site model of drug action. The double reciprocal plots of receptor-inactivation studies will display only a slight curvature as may be seen in previously published articles. Partial agonists may have 50% response doses lowe or higher than full agonists. The hypothesis that ternary complexes are formed with alpha 1-receptors could be tested more critically with receptor-inactivation studies using both antagonists and agonists. Partial inactivation of receptor and activator protein should reduce the binding of antagonist without altering the concentration needed to bind to 50% of the receptors. On the other hand, the concentration of agonist required to displace 50% of a bound antagonist is expected to increase. The proposal that contractile responses are proportional to the ternary complex concentration could be tested by fitting the ternary complex model to the data from studies of contractions induced by partial agonists as well as full agonists. PMID- 2886051 TI - Prevention of alpha 2-adrenergic inhibition on ADH action by pertussis toxin in rabbit CCT. AB - The present studies were performed to investigate the mechanism whereby alpha 2 adrenergic receptor occupancy inhibits the hydrosmotic action of antidiuretic hormone (ADH) in isolated cortical collecting tubules (CCT). The ADH ribosyltransferase activity of pertussis toxin (PT) was used to promote covalent modification in CCT Ni, the inhibitory regulatory protein of adenylate cyclase, which presumably mediates the alpha 2-adrenergic inhibition of water flow. Tubules preincubated with PT were studied after the addition of ADH and then after the superimposition of clonidine. In these studies, the inhibition of Jv (water absorption, nl X mm-1 X min-1) and Pf (water permeability coefficient, cm/s), by the addition of 10(-4) M clonidine to the bath, was attenuated by PT in a concentration-dependent manner. Reversal of the inhibitory action of clonidine was accomplished with a concentration of 1.0 micrograms/ml PT. To further elucidate the molecular basis of Ni-mediated transduction of the alpha 2 adrenergic signal, ADP-ribosylation studies were undertaken in membrane preparations of dissected CCT segments. PT ADP ribosylated a 40,000 Mr peptide which was proportional to the amount of membrane protein added. Furthermore, pretreatment of CCT during dissection with 0.5 micrograms/ml PT dramatically decreased the susceptibility of the subunit of Ni (alpha i) to be subsequently ADP ribosylated by PT, when compared with CCT preparations not previously treated with PT. Cholera toxin ADP ribosylated a 42,000 Mr peptide from CCT membranes and PT pretreatment did not interfere with the reaction. We conclude that CCT segments have both the pertussis and cholera toxin substrates and the effect of clonidine to attenuate ADH action is mediated through Ni. PMID- 2886050 TI - Immunocytochemical localization of peroxisomal enzymes in human liver biopsies. AB - The immunocytochemical localization of catalase and three enzymes of the peroxisomal lipid beta-oxidation system--acyl-CoA oxidase, the bifunctional protein enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase--in human liver biopsies was investigated by means of light and electron microscopy. The antisera raised against all four enzymes from rat liver cross reacted with the corresponding proteins in homogenates of human liver as revealed by immunoblotting. For light-microscopic localization in glutaraldehyde-fixed Epon-embedded material, the removal of resin and controlled digestion with trypsin was necessary. At the ultrastructural level specific labeling for all four antigens was found by the protein A-gold technique in peroxisomes of liver parenchymal cells fixed with formaldehyde-low glutaraldehyde concentrations and embedded in Lowicryl K4M. In biopsies fixed with glutaraldehyde and embedded in Epon, treatment with metaperiodate or etching with sodium ethoxide improved the immunolabeling. After such treatment catalase showed the most intense labeling and acyl-CoA oxidase the weakest, the two other proteins exhibiting an intermediate immunoreaction. In material postfixed with osmium only catalase could be visualized in peroxisomes. The immunocytochemical investigation of peroxisomal proteins in human liver biopsies provides a simple and highly promising approach for further elucidation of the pathophysiology of peroxisomal disorders. PMID- 2886053 TI - Beta-adrenergic blockade and intravenous nutrient-induced thermogenesis in lean and obese women. AB - Continuous respiratory exchange measurements were performed in nine obese and eight lean women for 1 h before, 3 h during, and 1 h after the intravenous administration of a nutrient mixture infused at twice the postabsorptive resting energy expenditure (REE). This experiment was conducted without or with beta adrenergic blockade (iv propranolol). Propranolol administration did not change the postabsorptive REE [i.e., 1.03 +/- 0.07 before vs. 1.01 +/- 0.02 kcal/min after administration in lean women and 1.16 +/- 0.04 vs. 1.15 +/- 0.03 kcal/min (NS) in obese women]. The mean overall thermogenic response expressed as a percentage of the infused energy was similar in both groups and was not significantly blunted after propranolol infusion [6.9 +/- 0.4 vs. 5.9 +/- 0.6% in the lean women and 7.5 +/- 0.5 vs. 7.1 +/- 0.6% (NS) in the obese women]. During beta-adrenergic blockade the rate of lipid oxidation decreased in the lean group but was unchanged in the obese group and the glycemic response to nutrient administration was significantly higher in both groups than without propranolol. It is concluded that beta-adrenergic blockade has no effect on REE and on intravenous nutrient-induced thermogenesis in both lean and obese women. PMID- 2886054 TI - Corelease of PHI and VIP by vagal stimulation in the dog. AB - Electrical vagal stimulation increased immunoreactive peptide histidine isoleucine (IR-PHI) and vasoactive intestinal polypeptide (IR-VIP) levels in the portal plasma in anesthetized dogs, depending on the stimulation frequency. Atropine failed to suppress the vagal release of IR-PHI and IR-VIP, whereas hexamethonium abolished the increase of both peptide immunoreactivities. Gel filtration profiles of IR-PHI and IR-VIP in the portal plasma obtained during vagal stimulation revealed major peaks of IR-PHI and IR-VIP eluting in the same positions as synthetic PHI-27 and VIP-28, respectively. These data demonstrate that PHI and VIP are coreleased by vagal stimulation via a nicotinic ganglionic mechanism. An additional peak of larger molecular weight IR-PHI was observed in gel filtration of the portal plasma obtained under higher frequency vagal stimulation, when measured by the N-terminal-specific PHI antiserum. The presence of this larger form of IR-PHI together with a PHI-27-like component was also demonstrated in tissue extracts of the entire length of the gastrointestine, particularly in higher concentration in the stomach. The structure and the physiological significance of this larger form of IR-PHI remains to be elucidated. PMID- 2886056 TI - Pyloric contribution to antroduodenal resistance to flow in the conscious dog. AB - We have developed a pneumatic resistometer to monitor antroduodenal resistance to flow for prolonged periods of time in conscious dogs. To investigate the specific contribution of the pylorus to antroduodenal resistance we compared resistance during fasting in four control dogs and in four dogs with extramucosal pyloric myotomy (1.5 cm long). After pyloric myotomy, as in controls, resistance to flow changed cyclically, being lowest during phase I and highest during phase III of the interdigestive motor cycle. Pyloric myotomy decreased resistance during phase III. Atropine (0.1 mg X kg-1 X h-1) administered during motor quiescence (phase I) reduced resistance in the control group (P less than 0.05) but not in myotomized animals. Bethanechol (0.2 mg X kg-1 X h-1) significantly increased resistance in both groups (P less than 0.05). We conclude that antroduodenal resistance to flow is related to cyclic interdigestive motility. The pylorus is the predominant determinant of antroduodenal resistance during motor quiescence, but its contribution diminishes markedly during motor activity. PMID- 2886055 TI - Potential mediation of somatostatin secretion from canine fundic D-cells by protein kinase c. AB - We examined the possible importance of protein kinase c-dependent mechanisms in mediating the stimulatory effects of gastrin and cholecystokinin (CCK) on the release of somatostatin-like immunoreactivity (SLI) from isolated canine fundic D cells. Diacylglycerides, presumably the products of phosphoinositide breakdown that activate protein kinase c, and phospholipase C, which catalyzes the production of endogenous diacylglycerides from membrane phospholipids, both stimulated SLI secretion in a dose-dependent fashion. Both classes of agents potentiated the actions of adenosine 3',5'-cyclic monophosphate-dependent agonists but not those of gastrin and CCK. The stimulatory effects of gastrin and CCK correlated with their abilities to enhance the incorporation of 32P into membrane phosphatidyl inositol and phosphatidic acid and promote the release of [3H]inositol trisphosphate from prelabeled D-cells, two parameters of phosphoinositide turnover. These data suggest that protein kinase c may serve to transduce the signals activated by gastrin and CCK in D-cells. PMID- 2886057 TI - Age-dependent biliary excretion of glutathione-related thiols in rats: role of gamma-glutamyltransferase. AB - The role of gamma-glutamyltransferase (GGT) in the biliary excretion of glutathione (GS) was studied in rats during postnatal development. Between 2 and 10 wk of age the biliary excretion of GS-related sulfur increased ninefold. During this period, alterations were observed in both hepatic GGT and the composition of GS-related thiols and disulfides in bile. For instance, between 3 and 4 wk of age, GGT activity and the biliary excretion of GS hydrolysis products (Cys-Gly and Cys) increased markedly, and the latter became the predominant sulfhydryls in bile. However, by 10 wk of age, the excretion rate of GS increased and exceeded the rate of excretion of Cys-Gly and Cys. The parallelism between hepatic GGT activity and the biliary excretion of GS-hydrolysis products during development suggests a role for GGT in the formation of biliary Cys-Gly and Cys. Furthermore, in 4-wk-old rats, inhibition of hepatic GGT by acivicin markedly decreased the biliary excretion of Cys-Gly and Cys and increased that of GS without influencing the excretion of total GS-related sulfur in bile. The biliary excretion of GS-related thiols was less responsive to acivicin in 2- and 7- to 10 wk-old rats, suggesting that GGT plays a smaller role in influencing biliary thiol composition at those ages. In summary, GS transported into bile is hydrolyzed in an age-dependent manner, however, the GGT-initiated hydrolysis of GS does not affect the biliary excretion of total thiols in rats. PMID- 2886058 TI - Increased vascular resistance during complement-activated plasma infusion in swine. AB - To investigate the acute effects of complement activation on blood flow, we infused complement-activated plasma into the femoral artery of the isolated hindlimb of 19 anesthetized swine. Femoral artery blood flow decreased abruptly, was lowest at 1 min of the infusion, and thereafter slowly increased despite continued infusion. There was no significant change in femoral artery pressure or femoral vein pressure, confirming an acute increase in vascular resistance. Control infusion of heat-decomplemented-activated plasma caused no change in pressure or flow. Slope of the femoral artery pressure-flow relationship during maximal vasodilation with adenosine was significantly lower after infusion of complement-activated plasma, confirming a persistent increase in vascular resistance. Neither the acute nor the persistent increase in vascular resistance was prevented by alpha-adrenergic blockade with phentolamine or granulocytopenia produced by cyclophosphamide. We conclude that complement-activated plasma infusion in the femoral circulation causes an abrupt increase in vascular resistance that persists during pharmacologically maximal vasodilation, is not due to alpha-mediated vasoconstriction, and is not altered by severe granulocytopenia. PMID- 2886059 TI - Free and conjugated catecholamines in dog pulmonary artery: presence and pharmacological action. AB - Free and conjugated forms of norepinephrine (NE) and dopamine (DA) were detected in dog pulmonary artery, and small amounts were released during 2-Hz electrical stimulation. Hydrolysis of the conjugates by acid boiling and by enzymes indicated that they were primarily sulfates, but traces of glucuronide may also have been present. After isolation by column chromatography, free and conjugated amines were quantitated using liquid chromatography with electrochemical detection. Pulmonary artery tissue contained (in ng) 1,240 +/- 100 free NE, 15 +/ 5 conjugated NE, 47 +/- 6 free DA, and 2 +/- 0.3 conjugated DA/g tissue (means +/- SE). When strips of pulmonary artery were immersed in [3H]NE small amounts of [3H]NE sulfate were synthesized. The release of conjugated NE was not calcium dependent but release was attenuated somewhat by tetrodotoxin. Removal of endothelium did not change tissue content of conjugated or of free NE nor the amounts measured in superfusate. Small amounts of free DA were also detected in tissues and in superfusate during stimulation, but only when calcium was present in the superfusion fluid. Norepinephrine sulfate was not a potent agonist at either pre- or postsynaptic alpha-receptors; the agonist activity seen with high concentrations of norepinephrine sulfate seems likely to have been due at least in part to trace contamination by free NE. PMID- 2886060 TI - Inhibition of renal sympathetic nervous activity by area postrema stimulation in rabbits. AB - This study investigated the effect of chemical and electrical stimulation of the area postrema on renal sympathetic nerve activity (RSNA), arterial pressure, and heart rate in urethan-anesthetized rabbits. Electrical stimulation of the area postrema at 2, 5, 10, 20, 40, and 80 Hz using constant currents of 7.5, 15, and 30 microA (pulse duration = 0.3 ms, train duration = 5 s) produced progressive decreases in RSNA and heart rate, with no consistent change in arterial pressure. To control for electrical activation of fibers of passage in or near the area postrema, L-glutamate was injected into the area postrema using glass micropipettes. Micropressure injection of L-glutamate (10 mM) in volumes of 5-10 nl produced rapid decreases in RSNA averaging 27 +/- 5% (P less than 0.05) accompanied by a small bradycardia. The effects of electrical stimulation of the area postrema, but not the adjacent nucleus tractus solitarius, were totally eliminated by micropressure injection of kainic acid (40 ng in 40 nl) into the area postrema. During continuous electrical stimulation of the area postrema using parameters that produced small decrements in RSNA and heart rate, the slope of the line relating baroreflex inhibition of RSNA to increases in arterial pressure during graded infusions of phenylephrine was significantly enhanced ( 6.77 +/- 1.30 vs. -3.81 +/- 0.66% RSNA/mmHg). These data are consistent with the hypothesis that activation of neurons in the area postrema results in an inhibition of RSNA. Furthermore, stimulation of the area postrema augments baroreflex inhibition of RSNA during increases in arterial pressure with phenylephrine. PMID- 2886061 TI - Pancreatic vagal nerve is receptive to somatostatin in rats. AB - To investigate whether somatostatin, one of the pancreatic islet hormones, influences the afferent firing activity of the vagus innervating the pancreas and whether there is any relevant morphological basis for the electrophysiological event, cyclic somatostatin-14 was injected into the rat pancreatic artery. The somatostatin injection at a physiological (0.61 pmol) or a pharmacological (3.05 pmol) dose significantly increased the afferent firing discharge rate of the pancreatic vagus in rats anesthetized with urethan and chloralose. The present histological examination disclosed a glomuslike neurovascular body in the rat peripancreatic sinusoidal vein. The body included many small corpuscles, and the corpuscle contained a structure like the afferent nerve ending. The immunohistochemical study revealed that the structure preferentially bound exogenous somatostatin. These electrophysiological and histological findings suggest that the vagal pancreatic nerve is receptive to somatostatin and that there exists a local neural monitoring system for somatostatin secreted from the islets. PMID- 2886062 TI - Clinical forms of severe tardive dyskinesia. AB - The authors describe 19 patients with severe tardive dyskinesia, 11 of whom had a diagnosis of affective or schizoaffective disorder rather than schizophrenia. Most patients had been receiving long-term neuroleptic treatment with few interruptions and had received only one or two different neuroleptics. Frequent eye blinking was the most prevalent prodromal sign of tardive dyskinesia (in seven patients). Four subtypes of tardive dyskinesia could be distinguished: choreoathetosis, tardive dystonia, blepharospasm, and tardive akathisia. Optimal pharmacotherapy most often consisted of combinations of neuroleptics, lithium carbonate, benzodiazepines, and antiparkinsonian drugs. However, after an average of 62 months, only five patients had markedly improved. PMID- 2886063 TI - L-dopa challenge and relapse in schizophrenia. AB - Neuroleptic administration has been shown to be superior to placebo in prolonging schizophrenic remission. However, individual patients are able to maintain long periods of remission in the absence of neuroleptic treatment, while others relapse soon after neuroleptic withdrawal. This study attempted to predict time to relapse in 28 schizophrenic patients withdrawn from neuroleptics and challenged with L-dopa for 7 days, then followed until relapse. Time to relapse correlated significantly with L-dopa-induced increase in BPRS score (p = .006). Five of six patients who responded to L-dopa relapsed within 4 weeks after L-dopa administration, while only four of 22 who did not respond relapsed in a comparable period. PMID- 2886064 TI - Pisa syndrome, or pleurothotonus. PMID- 2886065 TI - Absence of acquired tolerance to neuroleptics in schizophrenic patients. AB - Development of increased tolerance to neuroleptics was investigated in 38 neuroleptic-respondent schizophrenic patients. At 5- or 8-year follow-up, clinical global assessments were related to changes in neuroleptic doses. In 93% of the patients gradually increasing tolerance could be excluded. PMID- 2886066 TI - Depot neuroleptics for acutely psychotic patients. PMID- 2886067 TI - Neuroleptic malignant syndrome: facts and controversies. PMID- 2886068 TI - Symptoms of neuroleptic malignant syndrome. PMID- 2886069 TI - Seroepidemiologic study of giardiasis patients and high-risk groups in a midwestern city in the United States. AB - Serum antibodies to Giardia lamblia were measured in giardiasis patients, in groups at high risk for intestinal parasite infection, and in controls by an indirect fluorescent antibody (IFA) technique. Symptomatic patients had the highest antibody titers, and antibodies remained present for up to 18 months in persons with chronic infection. Indochinese refugees and male homosexuals with the acquired immunodeficiency syndrome (AIDS) and pre-AIDS had higher mean antibody levels than did healthy controls, whereas sewer and highway maintenance workers had levels similar to those of controls. Serum antibodies to Entamoeba histolytica measured by an indirect hemagglutination antibody technique were detected in only a few Indochinese refugees. We conclude that serology is a promising tool in G. lamblia epidemiology and that further population studies would be of interest. PMID- 2886070 TI - A ribosomal RNA gene probe differentiates member species of the Anopheles gambiae complex. AB - A 0.59 kilobase DNA fragment cloned from an rDNA cistron of the mosquito Anopheles gambiae can be used as a probe to differentiate between A. gambiae, A. arabiensis, and A. melas, three morphologically identical sibling species in the A. gambiae complex which otherwise can be reliably distinguished only by polytene chromosome banding patterns. Although all are important (and often sympatric) African malaria vectors, their relative roles in malaria transmission have thus far been difficult to assess. The probe, an EcoRI-SalI fragment from the 3' end of the 28S beta coding region of the cistron, is present in all three species, but the species differ uniquely with respect to the location of an EcoRI site in the nontranscribed spacer (NTS) downstream of the fragment. We have routinely used the probe to identify A. gambiae complex mosquitoes to species on the basis of genomic DNA extracted from individual air dried specimens. A single mosquito abdomen provides more than sufficient DNA for the assay, and neither eggs nor a bloodmeal in the abdomen interfere with DNA yield. Moreover, the DNA extraction procedure does not degrade the bloodmeal IgG, so the residual protein pellet can be used to identify the mosquito bloodmeal source. Since the rDNA cistron organization as detected by the probe does not differ between male and female mosquitoes, the probe can be used for either sex. Preliminary experiments show that the probe is equally useful for mosquito larvae and pupae. PMID- 2886072 TI - Carcinoids associated with multiple endocrine neoplasia syndromes. AB - Carcinoids occur in association with MEN types 1 and 2. To determine the relationship between carcinoids and MEN, we reviewed nine patients with carcinoids and other endocrine tumors. Analyzing these 9 patients and 56 other patients previously described in the literature, we found several clinically important relationships. In contrast to the usual midgut and hindgut origin, most carcinoids associated with MEN (69 percent) are of foregut origin (thymus 24 percent, bronchus 27 percent, stomach 3 percent, and duodenum 14 percent). Carcinoids are more commonly associated with MEN type 1 than MEN type 2 (59 patients and 6 patients, respectively). Thymic carcinoids associated with MEN are more common in men (15 versus 2), and most (82 percent) are malignant. Bronchial carcinoids associated with MEN are more common in women (15 versus 4), and most (74 percent) are benign. There is a strong association between thymic carcinoids and parathyroid tumors and between bronchial carcinoids and pituitary tumors. Most patients with carcinoids and hyperparathyroidism (82 percent) have had parathyroid hyperplasia or multiple parathyroid adenomas. Thus, carcinoids may occur in association with both MEN type I and MEN type II. MEN should be suspected in patients with foregut carcinoids. Patients with MEN and ectopic ACTH production should be considered to have bronchial carcinoids if they are female and thymic carcinoid if they are male. The thymus should be routinely removed in patients with MEN type I because of the possible presence of an ectopic parathyroid gland in this tissue and to prevent subsequent development of a carcinoid tumor. PMID- 2886071 TI - The role of gamma interferon in the generation of human macrophages cytotoxic for Entamoeba histolytica trophozoites. AB - Upon exposure to Entamoeba histolytica antigen, lymphocytes from patients treated for amebic liver abscess produce lymphokines which activate monocyte-derived macrophages to kill E. histolytica trophozoites. We now demonstrate that gamma interferon (IFN-gamma) is produced by these stimulated lymphocytes and is sufficient but not exclusively necessary to activate monocyte-derived macrophage amebicidal activity. Supernatants from mononuclear cells of 7 patients when stimulated with amebic antigen contained more IFN-gamma than comparable supernatants derived from control cells (1,862 U/ml vs. 174 U/ml geometric means, P less than 0.01); IFN-gamma levels were similar in patient and control supernatants following concanavalin A stimulation. Macrophages activated solely by partially purified IFN-gamma or recombinant human IFN-gamma (300 U/ml) killed 47% of virulent amebae by 6 hr at 37 degrees C. Monocyte-derived macrophages stimulated with lymphokines elicited by amebic antigen or concanavalin A killed 48% and 57% of axenic E. histolytica trophozoites, respectively, over 6 hr at 37 degrees C (P less than 0.001 for each compared to control). Macrophages incubated with the identical lymphokines, but in the presence of monoclonal antibody to IFN gamma, were only able to kill 18% and 27% of amebae, respectively, at 6 hr (P less than 0.05 to control or when antibody to IFN-gamma was not present). If antibody to IFN-gamma was added to the stimulating lymphokine, more macrophages died during interaction with amebae (P less than 0.05). In summary, IFN-gamma has a major but not exclusive role in activating human monocyte-derived macrophages in vitro to kill virulent E. histolytica trophozoites. PMID- 2886073 TI - Tuberous sclerosis: aberrant metabolism of ornithine, proline and glutamate in cultured fibroblasts. AB - To investigate aberrant metabolism of proline (Pro) and its precursors in tuberous sclerosis (TS), 6, 7 and 5 strains of control, TS (normal skin) and TS (tumor) fibroblasts, respectively, were cultured in Eagle's MEM containing dialyzed fetal bovine serum with or without 0.1 mM ornithine (Orn). Ornithine aminotransferase (OAT) activity was decreased in TS, especially in TS (tumor) after mild sonication treatment. The yield of the OAT protein was inhibited in TS (tumor) when cultured without Orn. Free glutamate (Glu) in the medium was significantly increased in TS (tumor). Free proline (Pro) in cells was significantly decreased in TS (tumor) when cultured with Orn, but protein-bound Pro was not. The relative concentration of free Glu to glutamine (Gln) in the medium and that of free Glu to Pro in cells cultured with Orn were increased in TS (tumor). These results suggest that the requirement for Orn, increased turnover of Pro to Glu and increased elimination of Glu into the medium occur in TS (tumor). Aberrant regulation or turnover of Pro and Glu metabolism may occur in TS, especially in tumor cells. PMID- 2886075 TI - Morphology and endocrine production of cells in the islets of Langerhans of the Chacma baboon. AB - Biopsies of the pancreas head, tail, and uncinate regions of 6 Chacma baboons (Papio ursinus) were processed for ultrastructural and immunocytochemical (ICC) studies using avidin-biotin peroxidase label for light microscopy (LM) and immunogold for electron microscopy (EM). Survey 0.5 micron sections of Spurrs resin embedded tissue revealed areas of suitable islets. Thin 100-nm sections were then cut and stained from the osmicated blocks for ultrastructural studies. For ICC investigations, 1 micron sections were immunolabeled for LM before areas were selected for thin sectioning for ultrastructural immunolabeling. The baboon endocrine pancreas ultrastructure was found to be similar to that of other mammals with minor differences in islet and secretory granule size and shape and in electron opacity of the secretory granule cores. Insulin glucagon, somatostatin and pancreatic polypeptide (PP) producing cells were described. A small number of cells were seen to contain both glucagon and PP and some D cells were observed to contain a few granules with both the appearance and immunoreactivity of A cell secretory granules. Statistical analysis of 100 secretory granule diameters of each of the 4 cell types in 6 baboons revealed significant differences (p less than 0.001) in size between all but those of the A and D cells. The insulin precursor subunit, C-peptide, and the glucagon precursor, glicentin, were each found together with the final hormone product in their respective secretory granules. The precursors were often located toward the periphery of the secretory granule, suggesting that the conversion of precursor to active hormone may be membrane associated. A nonrandom topographical association was observed between A and D cells, suggesting a strong functional implication. PMID- 2886074 TI - Human foetal kidney explants in serum-free organ culture. AB - The purpose of the work was to develop an in vitro model for the study of human kidney development. Human metanephric explants from foetuses 10-18 weeks of gestational age were cultured in serum-free Leibovitz L-15 medium without hormones. Under the current minimal conditions for growth, the system permitted to maintain the renal tissues in culture for periods up to 9 days, although no evident sign of morphological differentiation was observed. However, during the studied period the overall architecture of the explants was preserved as well as the ultrastructural features of cytoplasmic organelles. The incorporation of 3H thymidine and 3H-leucine indicated that DNA and protein synthesis was maintained or increased. Glycoprotein synthesis evaluated by 3H-glucosamine incorporation and radioautography continued in mesangium as well as in glomerular and tubular basement membranes. Alkaline phosphatase, gamma-glutamyltranspeptidase (brush border) and catalase (peroxisomes) activities remained histochemically active. The proposed organ culture system appears as a reliable and promising model that will provide basic data on the morphology and functional characteristics of the developing kidney. Since it is achieved in a completely controlled environment, it will permit to study the role of growth factors and hormones in proliferation and differentiation of the cell populations during development of the human foetal kidney. PMID- 2886077 TI - Relationship between single twitch depression and train-of-four fade: influence of relaxant dose during onset and spontaneous offset of neuromuscular blockade. AB - The characteristics of the train-of-four (TOF) response were studied electromyographically during onset and spontaneous offset of neuromuscular blockade with bolus doses of vecuronium (ED95, and ED95 X 2). During onset of blockade there was less fade with the larger than the smaller dose of vecuronium, demonstrating a variable and dose-related relationship between the ratio of height of the initial twitch, T1, and fourth twitch, T4. With both doses TOF fade was more pronounced during recovery than during onset of block, but at the same T1 values during offset, both doses were associated with similar degrees of fade during recovery. Thus with bolus doses of vecuronium the T4 ratio during recovery bears a fixed relationship to initial T1 depression that is independent of dose. PMID- 2886076 TI - Beta-blockade reverses regional dysfunction in ischemic myocardium. AB - To determine the protective effect of oxprenolol-induced beta-blockade on the compromised myocardium (critical constriction of the left anterior descending coronary artery) against the adverse effect of high concentrations of halothane, halothane dose-response curves were obtained in six dogs in each of three phases: preconstriction (control), critical constriction, and critical constriction with the addition of 0.3 mg/kg intravenous oxprenolol. The extent of depression of ventricular function was essentially the same in the three phases. However, at high halothane concentrations (2.0% inspired), the depression of systolic shortening in the compromised segment was significantly minimized after oxprenolol so that shortening was 10.2% +/- 1.8 instead of 6.5% +/- 1.4 (P less than 0.05); moreover the large increase in postsystolic shortening observed during critical constriction was abolished after oxprenolol. This suggests a protective effect of oxprenolol on regional myocardial function in the presence of critical constriction, possibly by an effect on myocardial metabolism or endocardial blood flow. PMID- 2886079 TI - Histaminoid reaction from vecuronium priming: a case report. PMID- 2886078 TI - Comparison of hemodynamic responses to isoproterenol infusion and surgical stress in patients given cardioselective and noncardioselective beta-adrenergic antagonists. AB - Recent studies have demonstrated the presence of physiologically active beta 2 receptors in the myocardium. We hypothesized that activation of cardiac beta 2 receptors by endogenously released epinephrine and norepinephrine during surgical stress would add to the positive chronotropic response mediated by beta 1 stimulation. Twenty patients scheduled for coronary artery bypass grafting were studied. Ten patients received a beta 1-selective antagonist (atenolol, 6; metoprolol, 4) and ten patients received a nonselective beta 1 and beta 2 antagonist (propranolol) preoperatively. An isoproterenol dose-heart rate response test was performed. After stabilization, general anesthesia was induced followed by tracheal intubation and surgery. Hemodynamic data were recorded before induction, 1 min after induction, 5 min after intubation, 1 min before and after skin incision, 1 min before and after sternotomy. The ten patients on cardioselective beta-blocker drugs had significantly greater increases in heart rate during isoproterenol administration than did the non-cardioselectively blocked group of patients. Heart rate responses to tracheal intubation and surgical stress were not significantly different between the two groups at any point. We conclude that changes in heart rate during perioperative stress are primarily mediated through activation of beta 1 receptors in the myocardium and that patients on either cardioselective or noncardioselective beta-blockers have similar protection to adrenergic-mediated stressful hemodynamic events. PMID- 2886080 TI - Pancuronium and vecuronium pharmacokinetics and pharmacodynamics in younger and elderly adults. AB - To evaluate the effect of aging on the distribution, metabolism, and neuromuscular junction sensitivity to pancuronium and vecuronium, the authors determined the pharmacokinetics and pharmacodynamics of these drugs in 12 healthy elderly subjects (70-84 yr) and 12 young adults (30-57 yr) during halothane nitrous oxide anesthesia. Plasma concentrations of the muscle relaxants were determined using a selective ion-monitoring mass spectrometric technique specific for the parent compound. For vecuronium, plasma clearance (3.7 +/- 1.0 and 5.2 +/ 0.8 ml X kg-1 X min-1, respectively), and volume of distribution at steady-state (179 +/- 31 and 244 +/- 38 ml X kg-1, respectively) were lower in the elderly than in young adults; values for distribution half-lives, elimination half-life, and sensitivity of the neuromuscular junction were similar for the two groups. For pancuronium, there were no statistically significant differences between groups for these pharmacokinetic or pharmacodynamic parameters. However, there was a trend toward reduced clearance (20%) and prolonged elimination half-life (16%) in the elderly as compared to the younger patients. The authors conclude that healthy elective surgical patients between the ages of 70 and 84 yr of age do not differ markedly from younger adults in their pharmacokinetic/pharmacodynamic response to vecuronium and pancuronium. PMID- 2886081 TI - The effect of phenytoin on the magnitude and duration of neuromuscular block following atracurium or vecuronium. AB - Patients chronically receiving anticonvulsants have been reported to be resistant to the long-acting competitive neuromuscular blockers. This study examines the effects of atracurium and vecuronium on 100 neurosurgical patients; 50 receiving chronic phenytoin therapy (group I) and 50 controls (group II). During O2/N2O/halothane anesthesia, five patients in each group were given a bolus of vecuronium 0.1 mg/kg, and a different five patients in each group were given atracurium 0.5 mg/kg, to produce neuromuscular blockade in excess of 95%. The time to maximum blockade and the recovery from atracurium was unaffected by phenytoin therapy. Recovery from vecuronium was enhanced in the phenytoin group, as demonstrated by the recovery index, defined as the time required for recovery from 25-75% of the control neuromuscular response (7.9 +/- 2.2 min compared with 17.8 +/- 5.1 min in controls, P less than 0.005). Similarly, the total duration of neuromuscular blockade, defined as recovery to 90% of control response, was significantly shorter in the phenytoin group (31.9 +/- 6.0 min compared with 69.7 +/- 12.9 min in controls, P less than 0.001). The remaining 40 patients from each group were given a preselected dose of either vecuronium (0.02-0.06 mg/kg) or atracurium (0.10-0.25 mg/kg) during anesthesia with O2/N2O/fentanyl, to generate dose-response curves for the relaxants. Using analysis of covariance, the slopes and elevations for atracurium were found to be essentially identical in the two groups; as were the calculated ED50 and ED95. Patients receiving chronic phenytoin therapy were resistant to vecuronium-induced neuromuscular blockade. With vecuronium, the dose-response curves for the two groups were parallel; the curve for phenytoin patients was shifted to the right.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886082 TI - DNA fingerprints of dogs and cats. AB - Human minisatellite probes consisting of tandem repeats of the 'core' sequence, a putative recombination signal in human DNA, cross-hybridize to multiple polymorphic fragments in dog and cat DNA to produce individual-specific DNA 'fingerprints'. Pedigree analysis shows that most of the DNA fragments detected in an individual are heterozygous, and that these fragments are derived from multiple dispersed autosomal loci. DNA fingerprints of cats and dogs should prove suitable for individual identification and for establishing family relationships. They are also suitable for rapid marker generation in large pedigrees and could be applied to linkage analysis in these animals. PMID- 2886083 TI - Genetic variation of the bovine thyroglobulin gene studied at the DNA level. AB - The bovine thyroglobulin gene has been analysed for variation using restriction endonucleases. Six independent restriction fragment length polymorphisms have been identified. One of these results most probably from a 2.5-kb deletion, the others being compatible with point mutations. We determined that an individual taken at random within the Belgian White and Blue breed is, on average, heterozygous for one out of 1700 nucleotides within the thyroglobulin gene. PMID- 2886084 TI - Surgical treatment of peptic ulcer disease before and after introduction of H2 blockers. AB - This retrospective study was undertaken to determine if the advent of H2 blockers has altered the surgical treatment and outcome of patients with peptic ulcer disease (PUD). The records of patients having surgery for PUD at Butterworth Hospital, Grand Rapids, Michigan, from 1971-73 (Group 1) and 1981-83 (Group 2) were reviewed. Data recorded included patient and disease characteristics, surgical procedures, morbidity, and mortality. There was a significant difference in mean age: 54 years in Group 1 and 60 years in Group 2. Group 2 had a higher incidence of concomitant medical illnesses. Indications for operation were predominantly of an emergent nature in Group 2, with a marked decline in elective surgeries from 75 per cent to 55 per cent. There was a 15 per cent incidence of nonsurgical complications in Group 2, as opposed to 9 per cent in Group 1. This study demonstrates that the use of H2 blockers and changes in patient characteristics have altered the surgical treatment and outcome of patients with PUD. PMID- 2886085 TI - Treatment of metastatic islet cell carcinoma with a somatostatin analogue (SMS 201-995). AB - We used an octapeptide analogue of somatostatin, SMS 201-995, in dosages ranging from 150 to 450 micrograms/d administered subcutaneously in three daily doses for 1 to 16 months, to treat 22 patients with advanced malignant islet cell carcinomas. Of the 22 patients, there were 9 with gastrinomas; 3 with glucagonomas; 4 with insulinomas; 1 with ectopic production of parathyroid hormone; and 3 with mixed syndromes. The only biochemical marker in 1 patient was pancreatic polypeptide, and 1 patient had no demonstrable peptide production from the tumor. In 14 patients, dramatic decreases in the levels of circulating peptides (insulin, vasoactive intestinal polypeptide, gastrin, and glucagon) have been accompanied by major alleviations of symptoms. Steatorrhea appears to be the most significant toxicity. This analogue of somatostatin may be appropriate for use as early therapy in patients who have symptoms from syndromes related to islet cell carcinomas but in whom there is no immediate threat from tumor progression. PMID- 2886086 TI - Adverse drug reactions associated with global cognitive impairment in elderly persons. AB - Adverse drug reactions causing cognitive impairment are an important problem in the elderly. Thirty-five patients with adverse drug reaction were identified among more than 300 patients evaluated for cognitive impairment and compared with patients without adverse drug reaction. Sedative hypnotic agents, especially long acting benzodiazepines, were the commonest drugs associated with cognitive impairment in this population. The number of drugs used, use of sedative hypnotics and antihypertensives, and falling were strongly associated with adverse reactions in logistic regression analyses. The relative odds of an adverse reaction associated with cognitive impairment increased as the number of prescription drugs increased, exceeding 9.0 for patients taking four or more prescription drugs. Adverse drug reactions are an important source of excess morbidity in patients with dementia or suspected dementia. Strategies that could minimize this problem include a high index of suspicion, drug-free trials in suspected cases, and careful monitoring of drug therapy. PMID- 2886087 TI - [Value of pinpointing mood swings in expanding the indications for lithium salts in schizophrenic psychosis]. PMID- 2886088 TI - False neurotransmitters and the effects of ethanol on the brain. PMID- 2886089 TI - Stimulation of serotonergic neuronal maturation after fetal mesencephalic raphe transplantation into the 5,7-DHT-lesioned hippocampus of the adult rat. AB - Neurotoxin lesioning of 5-HT fibers selectively induced the homotypic collateral sprouting of spared 5-HT fibers in the hippocampus. We have used this model to investigate the possibility that the neurotoxin-primed hippocampus will enhance the development of transplanted fetal serotonergic neurons in the brain. The neurotoxin 5,7-DHT, when microinjected into the FF, produced a specific and partial depletion of 5-HT in the hippocampus of adult rats. The ability of the 5,7-DHT-primed hippocampus to selectively support the neurochemical maturation of fetal serotonergic cells was tested by assaying the transplanted fetal raphe or LC 1 month after neuronal transplantation. The neurochemical maturation of fetal 5-HT and NE neurons was dramatically different when they were transplanted in the 5,7-DHT-FF-lesioned hippocampus as compared to the normal hippocampus. The transplanted 5-HT neurons had 480% more SHAU of [3H]5-HT and had a 250% greater content of 5-HT in the partially denervated hippocampus than in the normal hippocampus after 1 month. Furthermore, extracts obtained from lesioned hippocampus enhanced the 5-HT content of 5-HT neurons transplanted in the normal hippocampus, to a level similar to that seen in neurons transplanted in the lesioned hippocampus. In contrast, the implanted NE neurons of fetal LC had a lower NE level in the 5-HT partially denervated hippocampus than in normal hippocampus after 1 month in the host site. The growth of the NE transplants was not facilitated by the vacant postsynaptic space produced by the 5,7-DHT lesion. These results suggest that the 5-HT denervation triggered a trophic signal selectively enhancing the development of the 5-HT neurons but not the NE neurons. Our results are consistent with previous studies showing homotypic collateral sprouting in 5,7-DHT-primed hippocampus. PMID- 2886090 TI - Morphological and immunocytochemical characteristics of PC12 cell grafts in rat brain. PMID- 2886091 TI - Ultrastructural and immunohistochemical analysis of fetal mediobasal hypothalamic tissue transplanted into the aged rat brain. AB - MBH tissue, which included the hypothalamic arcuate nucleus of fetal or neonatal rats, was transplanted into the third ventricle of aged (21-30-month-old) female rats. The brain and ovaries of each recipient were examined histologically 3 or 4 weeks after transplantation. Four grafted MBH tissues were examined ultrastructurally and immunohistochemically 4 weeks after transplantation. The appearance of the MBH grafts was similar to that of normal neural tissue. The neuropil in the grafts was fully occupied with numerous axons, dendrites, and glial processes. A number of axodendritic shaft and spine synapses were observed in the neuropil. Immunohistochemical analysis with antiserum to TH revealed stained (immunoreactive) neuronal perikarya and processes in the grafts. TH immunoreactive processes originating from the TH-positive neurons in the grafts could be seen to extend across the graft-host interface. The ovaries of six out of nine females that received MBH grafts exhibited follicles of various sizes and healthy appearing corpora lutea. On the other hand, some follicles and masses of interstitial cells were prominent in the ovaries of the intact animals or controls that had received cortical grafts. In the females that received MBH grafts, the ovarian weight was significantly greater than that in the controls. These results suggest that the neural substrates in fetal MBH tissue can survive and develop well in the aged rat brain and that MBH grafts may play some role in the recovery of declined ovarian function in aged female rats. PMID- 2886092 TI - Reversal of parkinsonism by fetal nerve cell transplants in primate brain. PMID- 2886093 TI - Lymphoid system as a regulator of morphostasis and hormonal modulation of these functions. PMID- 2886094 TI - Immunomodulatory action of somatostatin. AB - The influence of somatostatin (SST) on spontaneous proliferation and cyclic AMP level in mouse spleen lymphocytes and on inhibition of human leukocyte migration was studied. The rate of [3H]thymidine incorporation was used as an index of proliferation. It was found that lower concentrations of SST/10(-9) and 10(-8)M, inhibited the splenocyte proliferation. In contrast, a higher SST concentration, 10(-7)M, exerted a stimulatory effect. SST in concentrations from 10(-9) to 10( 6)M did not influence cyclic AMP levels in mouse splenocytes; a significant decrease of cyclic AMP was found after the exposure to superactive SST analog RC 102-2H in concentrations 10(-8) and 10(-7)M. SST, 10(-7)M, and RC-102-2H, 10( 7)M, significantly enhanced the migration inhibition of human leukocytes induced by the exposure of leukocytes to cardiac antigen or phytohemagglutinin. The data provide evidence for an immunomodulatory action of SST. PMID- 2886095 TI - Benzodiazepines and PK 11195 exert immunomodulating activities by binding on a specific receptor on macrophages. PMID- 2886096 TI - The modulation of immunologic potential of splenocytes in induction of local GVHR by somatostatin. PMID- 2886098 TI - Is dopamine related to immunologic changes in schizophrenic patients? PMID- 2886097 TI - Pharmacologic interventions to antagonize stress-induced immune consequences. PMID- 2886099 TI - Hypothalamic neurotransmitters in relation to normal and disturbed eating patterns. AB - An integrated hypothesis for explaining eating behavior must consider the organism as a whole, the multiple brain neurotransmitters and structures involved, and the diverse variables that have impact on the expression of the behavior. In this review, we will examine a variety of brain monoamines and neuropeptides, in terms of their impact on eating, and also relate these neurochemical systems to peripheral autonomic and endocrine functions. We will propose how these central and peripheral systems may interact under normal and generally stable conditions, as well as how they may help to maintain energy or nutritional homeostasis under stressful conditions, in particular, food deprivation. PMID- 2886100 TI - The place of animal models and animal experimentation in the study of food intake regulation and obesity in humans. PMID- 2886101 TI - Dietary treatments that affect brain neurotransmitters. Effects on calorie and nutrient intake. PMID- 2886103 TI - Formation of several enzymes associated with alkane utilization by yeast. PMID- 2886102 TI - Induction of obesity by psychotropic drugs. AB - Evidence from published studies and clinical experience indicates that neuroleptic drugs, tricyclic and heterocyclic antidepressants, monoamine oxidase inhibitor antidepressants, and lithium all possess varying abilities to increase appetite, stimulate carbohydrate craving, and cause weight gain over prolonged periods of administration. Sedatives and benzodiazepine-type antianxiety drugs fail to stimulate appetite or induce weight gain, and it is unlikely that the sedative or calming effects of other psychotropic drugs contribute significantly to changes in appetite or weight. Studies of the endocrine and metabolic aspects of psychotropic drugs suggest that these mechanisms do not contribute significantly to explaining the observed effects on appetite or weight. Numerous studies indicate that a wide variety of compounds, including the serotonin precursor, tryptophan, the serotonin receptor stimulant, fenfluramine, and the serotonin reuptake inhibitor, fluoxetine, are all capable of decreasing carbohydrate hunger, reducing consumption of carbohydrate-rich foods, and inhibiting weight gain in humans and animals. Widely divergent psychotropic drugs produce antagonistic effects at serotonin receptor sites, and it is likely that this action contributes to their ability to stimulate appetite, carbohydrate craving, and weight gain. Those psychotropic drugs that inhibit serotonin reuptake mechanisms, increasing serotonin activity within the central nervous system, either fail to stimulate carbohydrate hunger and weight gain or are actually capable of decreasing carbohydrate craving and facilitating weight loss. Because many antidepressants, including trazodone and amitriptyline, the neuroleptic, chlorpromazine, and the mood stabilizer, lithium, may all, under some circumstances, inhibit serotonin reuptake mechanisms and may simultaneously block serotonin receptor sites, their effects on appetite and weight gain may represent a balance between serotonergic and antiserotonin activities. Monoamine oxidase inhibitors, which slow the metabolic degradation of monoamines, including serotonin and norepinephrine, allow for increased levels of these neurotransmitters within the brain. It is conceivable that the relative noradrenergic effect related to an amphetamine-like structure of tranylcypromine may explain its lesser ability to stimulate appetite and weight gain than the appetite and weight effects observed with phenelzine. Furthermore, the production of dry mouth and thirst by psychotropic drugs appears to contribute to weight gain, secondary to consumption of high-calorie beverages.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2886105 TI - [Digital subtraction angiography]. PMID- 2886104 TI - Proteolysis in the gut of mosquito larvae results in further activation of the Bacillus sphaericus toxin. AB - Gut proteases from the larvae of the mosquito Culex pipiens convert the 43 kilodalton (kDa) toxin from Bacillus sphaericus 2362 to a 40-kDa peptide. The 50% lethal concentration of this peptide for tissue culture-grown cells of Culex quinquefasciatus was 1.0 microgram/ml (as determined by the intracellular ATP assay), 54-fold less than that of the 43-kDa peptide. Gut proteases from Anopheles gambiae and Aedes aegypti, as well as bovine pancreatic trypsin, also converted the 43-kDa protein to a 40-kDa peptide which was indistinguishable from the peptide formed by the proteases from C. pipiens with respect to its toxicity to tissue culture-grown cells of C. quinquefasciatus. Evidence for the in vivo conversion of the 43-kDa protein to the 40-kDa peptide was also obtained from experiments in which larvae of C. pipiens, Anopheles gambiae, and Aedes aegypti were fed crystals from B. sphaericus 2362. By using the exclusion of trypan blue as an indication of cell viability, it was shown that chitobiose, chitotriose, N acetylmuramic acid, and N-acetylneuraminic acid decreased the toxicity of the 40 kDa peptide (from 100 to 50% mortality at about 10 mM concentrations of these sugars). Muramic acid, N-acetylgalactosamine, and N-acetylglucosamine were less effective, while several sugars had no effect, suggesting that the 40-kDa toxin binds to specific receptors on the cell membrane. The 40-kDa protein was less toxic to tissue culture-grown cells of Anopheles gambiae and Aedes dorsalis, and the same sugars which reduced the toxicity for cells of C. quinquefasciatus were also effective in reduction of toxicity for these cell lines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886106 TI - [Enzyme alterations during chemical hepatocarcinogenesis]. AB - Biochemical phenotypes such as the forms of enzyme proteins alter during the promotion and progression stages in chemical hepatocarcinogenesis. Many enzymes or isoenzymes have been identified as markers of (pre) neoplastic hepatic tissues and used for analysis of the carcinogenic process. The levels of hepatic isoenzymes decrease and those of prototypic or fetal isozymes increase during the progression of hepatocarcinogenesis. Some drug-metabolizing enzymes are also very variable at the promotion stage in rat chemical carcinogenesis; Phase I enzymes such as cytochrome P-450 decrease and Phase II (iso)-enzymes such as UDP glucuronyl-transferase, glutathione S-transferase (GST) and gamma-glutamyl transpeptidase (gamma-GTP) increase. A new neutral GST form with pI 7.0 (GST-P) has been identified by us as one of the best markers for rat chemical hepatocarcinogenesis. GST-P is a homodimer consisting of a subunit (Mr 26,000, more accurately 23,307, and pI 6.7), the smallest among rat GST subunits, and differs immunochemically from any other GST form. It is present in very low levels in normal rat liver and is not inducible by most drugs including carcinogens without the appearance of preneoplastic hepatocyte nodules (HN) but it is increased by several ten-fold in HN-bearing liver and hepatomas induced by different carcinogens. Immunohistochemically, it is localized in HN and very early and small GST-positive foci are detectable using anti-GST-P antibody. (Pre) neoplastic hepatic lesions induced by nongenotoxic carcinogens such as hypolipidemic peroxisome-proliferating agents do not express GST-P as well as gamma-GTP. PMID- 2886108 TI - The internal mammary artery as a bypass graft? PMID- 2886109 TI - Anatomical studies to support the expanded use of the internal mammary artery graft for myocardial revascularization. AB - The internal mammary artery pedicle graft is frequently used for coronary bypass. Five internal mammary artery pedicle grafts, harvested but not utilized for coronary bypass, underwent histological examination. The histological studies demonstrated that the vasa vasorum were confined to the adventitia and did not penetrate the media of the internal mammary artery. These observations indicate that the media is nourished entirely from the lumen and suggest that harvesting the internal mammary artery as a free graft would not subject the wall of the artery to ischemic injury. Subsequent to these studies, we used the right internal mammary artery as a free graft to revascularize the distal circumflex coronary artery in 12 patients. The free graft was anastomosed to marginal branches of the circumflex and was then brought up to the left internal mammary artery pedicle graft and anastomosed end-to-side. This procedure has not resulted in excessive postoperative bleeding or sternal infections, and has relieved the anginal syndrome in all 12 patients. PMID- 2886107 TI - Molecular abnormalities of collagen in human disease. PMID- 2886110 TI - Prediction of relapse in schizophrenia. AB - Despite the proven efficacy of neuroleptic drugs in the acute and maintenance pharmacotherapy of schizophrenia, practical methods for identifying patients who require neuroleptic treatment to prevent relapse are lacking. This study evaluated the use of a methylphenidate challenge test to predict the outcome in 34 stable outpatients with schizophrenia receiving neuroleptic treatment. Patients received two infusions, one of methylphenidate and one of placebo, in randomized order one week apart while receiving neuroleptic treatment and again three weeks after drug withdrawal. Behavioral, cardiovascular, and neurologic responses were evaluated before and after infusion under double-blind conditions. Patients were then followed up without medication for 52 weeks or until symptom recurrence. The results indicate that specific measures, including behavioral response to methylphenidate, presence of tardive dyskinesia, and, under specific pharmacologic conditions, tardive dyskinesia, blink-rate, and pulse-rate responses to methylphenidate, are associated with time and propensity to relapse following neuroleptic withdrawal. These measures may be potentially useful in the identification of candidates for neuroleptic withdrawal and/or dosage-reduction treatment strategies. PMID- 2886111 TI - [Oxabenzomorphanes: synthesis, reactions and CNS action of 2,6-methanotetrahydro 3-benzoxocines]. PMID- 2886112 TI - Studies of human retroviruses in relation to adult T-cell leukaemia, acquired immune deficiency syndrome, and multiple sclerosis. AB - Studies of adult T-cell leukaemia virus/human T-cell leukaemia/lymphotropic viruses (ATLV/HTLV-I) in Japan indicate that the virus is involved only with the development of ATL. By contrast, reports from the U.S.A. about HTLV have from time to time claimed that related HTLV are concerned not only with ATL of black persons, but also with a wide range of diseases, such as mycosis fungoides/Sezary's syndrome, T-cell hairy cell leukaemia, acquired immune deficiency syndrome (AIDS) and also multiple sclerosis. Using morphological, biological, serological and molecular hybridisation studies, we were able to confirm that the viruses implicated in the development of ATL and AIDS are distinct and that ATLV/HTLV-I is involved only in ATL, and HIV/LAV/HTLV-III only in AIDS. In vitro, ATLV/HTLV-I transformed and immortalised T-cells, while HIV/LAV/HTLV-III killed our T-cells. Failure to detect any serological cross reaction indicates that all the structural proteins are different. Likewise, Southern blot studies failed to reveal any cross-hybridisation. Sixty patients with multiple sclerosis failed to reveal any association with ATLV/HTLV-I or with HIV/LAV/HTLV-III. Our conclusion is that ATLV/HTLV-I is involved only in ATL of Japanese and of some black persons of African origin, and that HIV/LAV/HTLV-III is associated only in AIDS. PMID- 2886114 TI - Attitudes and knowledge of nursing staff in relation to management of postoperative pain. AB - The effectiveness of pain control following surgery is notoriously difficult to assess, but objective assessment by nursing staff has been found to correlate reasonably well with subjective patient assessment. A study was designed to investigate the attitudes and knowledge of 86 qualified nursing staff in relation to postoperative pain management. Overall knowledge was sound to a point, but there were some obvious deficiencies in practical application; for example, 25% of staff would wait until a patient was in severe pain before using a prescribed (charted) analgesic. Additionally, almost three-quarters of staff felt that, in general, postoperative patients received adequate pain relief, while the great majority felt that prescription writing could be improved, mainly by improved legibility and clarity of actual instructions. The results suggest that the aim of postoperative pain management--that is, the provision of adequate analgesia- may need to be more strongly defined in nursing education. PMID- 2886113 TI - Detection of hantaviruses with RNA probes generated from recombinant DNA. AB - Radiolabeled RNA probes generated from cDNA clones of the M and S genome segments of Hantaan virus readily detected Hantaan virus and two isolates from Korean hemorrhagic fever patients but were less effective in detecting four other hantaviruses. PMID- 2886115 TI - Spatial learning in the rat: impairment induced by the thiol-proteinase inhibitor, leupeptin, and an analysis of [3H]glutamate receptor binding in relation to learning. AB - Rats were given continuous intraventricular infusion of saline or the thiol proteinase inhibitor leupeptin, via subcutaneously implanted osmotic minipumps, while being trained on a spatial learning water task using spaced trials. Leupeptin caused overnight forgetting during training, but performance eventually reached asymptote in both groups. A retention test conducted 48 h later to assess spatial memory revealed no significant group differences, but did cause, in saline-treated rats only, a disruption of subsequent retraining back to the correct spatial location. The groups showed no differences in Cl-dependent [3H]glutamate receptor binding to hippocampal or entorhinal cortex membranes subsequent to training. In a second experiment, normal rats trained on the same task also showed no differences in Cl-dependent [3H]glutamate binding relative to rats exposed to the water task but given random spatial position training and handled controls. The results are discussed in relation to the hypothesis of Lynch and Baudry (Science (1984) 224, 1057-1063) that a calcium-dependent thiol proteinase is involved in memory formation through its ability to modify glutamate receptor distribution and dendritic spine shape. PMID- 2886116 TI - Tissue protection by adrenergic blockade in the calcium paradox? AB - In a graded model of the calcium paradox phenomenon (minimal and total) the presence of the beta-blocker propranolol (5 X 10(-6) M) in the perfusion media (10 min prior to, during and 5 min following calcium-free perfusion) had no effect upon tissue injury. Propranolol pretreatment (three days prior to the experiments) significantly reduced the myocardial enzyme release during calcium repletion in the minimal calcium paradox. The presence of the alpha 1-blocker prazosin (1 X 10(-7) M) in the perfusion media (10 min prior to, during and 5 min following calcium-free perfusion) afforded no protective effects. It is concluded that the release of endogenous catecholamines may not be an important factor contributing to myocardial injury in the calcium paradox, and that consequently beta- or alpha 1-adrenergic blockade has little if any protective properties in this form of myocardial injury. PMID- 2886117 TI - Spontaneous oscillation of the systemic arterial pressure during cardiopulmonary bypass in man. The effects of some drugs used during the operation. AB - Despite the fact that the blood flow maintained during cardiopulmonary bypass is rather steady in the extracorporeal pump output, the arterial pressure under high dose fentanyl anaesthesia quite often shows sinusoidal oscillations. In the present study the duration of an oscillatory cycle was on average 17.6 +/- 3.6 s, its amplitude 7.3 +/- 1.6 mm Hg and mean systemic arterial pressure 75 +/- 12 mm Hg. The oscillation is affected by the drugs used under bypass conditions. In our series of clinical observations the blood pressure oscillation disappeared under the influence of chlorpromazine, phentolamine, droperidol, and enflurane, and it disappeared or at least was distinctly attenuated under fentanyl, thiopental, diazepam, sodium nitroprusside, nitroglycerin, acebutolol, and potassium chloride. Pancuronium, atropine and furosemide appeared to be practically ineffective. In spite of the fact that the drugs used affected several sites of the sympathetic efferent chain, the disappearance and attenuation of the oscillation were associated with a simultaneous decrease of blood pressure. Hence, it is suggested that the occurrence of the oscillations requires some level of peripheral vascular tone. PMID- 2886118 TI - Characteristics of beta A chromosome haplotypes in Japanese. AB - DNA polymorphism patterns linked to the beta A-globin gene were analyzed in healthy Japanese using four different restriction endonucleases. The chromosomes with the beta A-globin gene were mapped through an evaluation of the presence of seven different restriction sites (HincII 5' to epsilon; HindIII in G gamma and A gamma; HincII in, and 3' to, psi beta 1; AvaII in beta; Bam-HI 3' to beta). Among 36 chromosomes analyzed, 20 chromosomes had a haplotype of [+-----+]. Among 55 individuals examined, 7 possessed a homozygous haplotype of [+-----+]. All Japanese with the A gamma T-globin gene had a subhaplotype of [-++-+] 5' to the delta-globin gene. Their major haplotypes were [-++-+-+] and [-++-++-]. It was expected that the presence of the A gamma T-globin gene in Japanese may be deduced from subhaplotypes 5' to the delta-globin gene. PMID- 2886119 TI - The invasive adenylate cyclase of Bordetella pertussis. Properties and penetration kinetics. AB - Bordetella pertussis, the causative organism of whooping cough, produces a calmodulin-sensitive adenylate cyclase. Confer & Eaton [(1982) Science 217, 948 950] have shown that an extract from B. pertussis increases intracellular cyclic AMP levels in neutrophils and suggested that this increase is caused by the bacterial adenylate cyclase which penetrates these cells. We demonstrate in the present study that adenylate cyclase activity in lysates from lymphocytes exposed to a partially purified preparation of the bacterial enzyme has properties completely different from those of the intrinsic membrane-bound enzyme. Adenylate cyclase activity in lysates from lymphocytes exposed to the invasive enzyme is insensitive to N-ethylmaleimide, readily inactivated by acetic anhydride and relatively stable to SDS. Similar properties are exhibited by the bacterial enzyme itself. By contrast, the intrinsic membrane-bound enzyme activated by forskolin and guanosine 5'-gamma-thiotriphosphate is sensitive to N ethylmaleimide and SDS and relatively stable to acetic anhydride. This strongly supports the notion that B. pertussis adenylate cyclase penetrates cells. Using the partially purified preparation of the invasive enzyme, we have studied the kinetics of its penetration. The intracellular catalytic activity reaches a steady state within 20 min, irrespective of enzyme or cell concentration. Steady state levels are maintained for at least 2 h provided that the invasive enzyme is present in the incubation medium. Upon its removal, a rapid decrease (t1/2 approximately equal to 15 min) in the intracellular cyclase level is observed. This decrease reflects intracellular inactivation of the bacterial enzyme and is not caused by the release of the enzyme to the cell medium. PMID- 2886120 TI - The invasive adenylate cyclase of Bordetella pertussis. Intracellular localization and kinetics of penetration into various cells. AB - The penetration of Bordetella pertussis adenylate cyclase into various mammalian cells exhibits similar kinetics; the accumulation of both intracellular cyclase activity and cyclic AMP is rapid, reaching constant levels after 15-60 min of incubation. The kinetics of enzyme penetration into turkey erythrocytes is different; cyclase activity and cyclic AMP accumulate linearly and do not reach constant levels even after 6 h of incubation. In the preceding paper [Friedman, Farfel & Hanski (1987) Biochem. J. 243, 145-151] we have suggested that the constant level of intracellular cyclase activity reflects a steady state formed by continuous penetration and intracellular inactivation of the enzyme. In contrast with other mammalian cells, no inactivation of cyclase is observed in turkey erythrocytes. These results further support the notion that there is continuous penetration and deactivation of the invasive enzyme in mammalian cells. A 5-6-fold increase in specific activity of the invasive cyclase is detected in a pellet fraction of human lymphocytes in which a similar increase in specific activity of the plasma-membrane marker 5'-nucleotidase is observed. A similar increase in the invasive-cyclase specific activity is detected in a membrane fraction of human erythrocytes. Cyclase activity in a membrane-enriched fraction of human lymphocytes reached a constant level after 20 min of cell exposure to the enzyme. Similar time courses were observed for accumulation of cyclase activity and cyclic AMP in whole lymphocytes [Friedman, Farfel & Hanski (1987) Biochem, J. 243, 145-151]. We suggest therefore that cyclic AMP generation by the invasive enzyme as well as the intracellular inactivation process occur while it is associated with a membrane fraction identical, or closely associated, with the plasma membrane. PMID- 2886121 TI - Essentiality of Glu-48 of ribulose bisphosphate carboxylase/oxygenase as demonstrated by site-directed mutagenesis. AB - Previous reports provide indirect evidence for the presence of Glu-48 at the active site of ribulose bisphosphate carboxylase/oxygenase from Rhodospirillum rubrum. This possibility has been examined directly by replacement of Glu-48 with glutamine via site-directed mutagenesis. This single amino acid substitution does not prevent subunit association or ligand binding. However, the Glu-48 mutant is severely deficient in catalytic activity, exhibiting a kcat only 0.05% that of wild-type enzyme. These results demonstrate that Glu-48 is positioned at the active site and suggest that it serves a functional role. In conjunction with previous studies, the discovery of essentiality of Glu-48 argues that the active site is located at an interface between subunits. PMID- 2886122 TI - Adriamycin resistance in HL60 cells in the absence of detectable P-glycoprotein. AB - Previous studies have shown that the development of multi-drug resistance in cell lines treated with chemotherapeutic agents is closely associated with the overexpression of a 170-180 kilodalton surface membrane glycoprotein (P glycoprotein). In the present study a monoclonal antibody against the P glycoprotein was used to determine if this protein is overexpressed in multi-drug resistant HL60 cells. Using either indirect immunofluorescent staining or immunoblot analysis P-glycoprotein could not be detected in HL60 cells isolated for resistance to adriamycin. In contrast HL60 cells isolated for resistance to vincristine contain the P-glycoprotein and the amount of this material increases with increasing levels of resistance. These studies thus demonstrate adriamycin resistance in P-glycoprotein negative HL60 cells. Furthermore adriamycin and vincristine are found to have distinct effects in inducing overexpression of P glycoprotein in the HL60 cell line. This information could be useful in the development of therapeutic strategies for the treatment of certain forms of cancer. PMID- 2886123 TI - Involvement of endopeptidase 24.15 in the inactivation of bradykinin by rat brain slices. AB - The effect of peptidase inhibitors on the degradation of [3H]-bradykinin by rat hypothalamic slices was studied using HPLC to separate and identify the products. The degradation appears to be mainly mediated by an enzyme which cleaves the peptide at the Phe5-Ser6 bond and is inhibited by 1,10-phenanthroline, dynorphin(1-13) and carboxyphenylethyl-Ala-Ala-Phe-p-aminobenzoate. This suggest the involvement of a membrane bound variant of the soluble metalloendopeptidase (EC3.4.24.15) isolated from rat brain which degrades neurotensin, angiotensin and other neuropeptides as well as bradykinin. PMID- 2886124 TI - Inhibition of NADH oxidation by pyridine derivatives. AB - The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, an impurity in an illicit drug, is expressed after its oxidation to 1-methyl-4-phenylpyridinium by monoamine oxidase. The pyridinium is concentrated by carrier-mediated transport into the mitochondria where it inhibits NADH dehydrogenase and, hence, ATP synthesis. Some structurally related compounds have been tested for their effect on the oxidation of NAD+-linked substrates in intact mitochondria, and for the inhibition of the accumulation of the pyridinium into mitochondria and of NADH dehydrogenase activity in a membrane preparation. Some pyridine derivatives are more inhibitory to NADH dehydrogenase than is 1-methyl-4-phenylpyridinium but these are not concentrated into mitochondria by the uptake system. 4 Phenylpyridine, one of the most effective inhibitors, both occurs naturally and is an environmental pollutant. PMID- 2886125 TI - In vivo dopamine receptor assessment for clinical studies using positron emission tomography. PMID- 2886126 TI - Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain. AB - 3,4-Methylenedioxymethamphetamine (MDMA) is a recently popularized recreational drug, although some have advocated its psychotherapeutic potential. Since the pharmacology of MDMA is largely uncharacterized, the stereochemical profiles of MDMA and some of its homologs were derived on inhibition of synaptosomal uptake of [3H]monoamines and compared to those of amphetamine and the hallucinogenic phenylisopropylamine 2,5-dimethoxy-4-methylamphetamine (DOM). In contrast to the 5-fold stereoselectivity observed with amphetamine, only the S-(+) enantiomer of MDMA and 3,4-methylenedioxyamphetamine (MDA) inhibited [3H]dopamine uptake into striatal synaptosomes. Neither stereoisomer of the alpha-ethyl homolog of MDMA, N methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB), inhibited [3H]dopamine uptake. The two stereoisomers of amphetamine and the MDMA-related compounds were equipotent in inhibiting [3H]norepinephrine uptake into hypothalamic synaptosomes. Both stereoisomers of MDMA, MDA and MBDB were potent inhibitors of [3H]serotonin uptake into hippocampal synaptosomes, but only S-(+)-amphetamine produced an appreciable inhibition of [3H]serotonin uptake. Neither stereoisomer of DOM inhibited synaptosomal uptake of any [3H]monoamine. These results suggest that MDMA and its homologs may be more closely related to amphetamine rather than to DOM in their biochemical mode of action. The pronounced effects of the methylenedioxy-substituted compounds on [3H]serotonin and [3H]norepinephrine uptake implicate these neurotransmitters in the pharmacological effects of these drugs. PMID- 2886127 TI - Neuroleptic-like effects of the l-isomer of fenfluramine on striatal dopamine release in freely moving rats. AB - l-Fenfluramine (l-F) was studied for its ability to release dopamine (DA) and its metabolites in freely moving rats through the trans-striatal dialysis technique. l-F's effect on striatal DA release was also studied in animals made tolerant to the effect of haloperidol by chronic treatment (1 mg/kg i.p. twice daily for 11 days and 48 hr wash-out) with the neuroleptic or pretreated with 300 mg/kg i.p. gamma-butyrolactone (GBL). Five and 10 mg/kg l-F dose-dependently increased the release of DA and its metabolites with a pattern of effects similar to that observed with neuroleptic drugs. The dose of 20 mg/kg l-F had the same effect as 10 mg/kg. Repeated haloperidol treatment reduced the basal release of DA and its metabolites and a much smaller amount of DA and metabolites was released by l-F (10 mg/kg i.p.) and haloperidol (0.1 mg/kg i.p.) in animals treated with haloperidol than in controls. GBL 300 mg/kg i.p. reduced basal DA release by about 50%. When 10 mg/kg l-F, 0.1 mg/kg haloperidol and 0.25 mg/kg d-amphetamine were injected i.p. 40 min after GBL, l-F and haloperidol did not significantly raise DA release in GBL-treated rats whereas a significant effect was observed at various times after d-amphetamine. The data show that l-F resembles haloperidol in its ability to release DA and its metabolites from the corpus striatum of freely moving rats. The cross-tolerance between haloperidol and l-F for their effect on DA release suggests that a common site is involved in the mechanism of these drugs. PMID- 2886129 TI - Psychopharmacological profile of the new cognition enhancing agent exifone in the mouse. AB - Hexahydro-2,3,4,3',4',5'-benzophenone (exifone, Adlone), a novel compound proposed for treating cognitive dysfunction in geriatric patients, was tested in a battery of standard psychopharmacological tests in the mouse. The results indicated that the compound was non-toxic and induced no signs of overt stimulation or sedation after acute administration of oral doses up to 1024 mg/kg. The compound was devoid of anxiolytic, anticonvulsant or classical neuroleptic activity and did not antagonize the effects of reserpine or a high dose of apomorphine, two tests indicative of classical antidepressant activity. On the other hand, exifone clearly decreased the duration of immobility in the tail suspension test and antagonized the hypothermia induced by a low dose of apomorphine. The compound shortened the duration of barbital induced sleep without affecting the duration of sleep induced by pentobarbital. The effects observed suggest that exifone is not devoid of psychotropic activity and might possess some properties of an atypical antidepressant. PMID- 2886128 TI - Comparison of the effects of the new anxiolytic suriclone and benzodiazepines on motor function and electroencephalogram. AB - (6-(7-Chloro-1,8-naphthyridin-2-yl)-7-oxo-2,3,6,7-tetrahydro-5H- 1,4- dithiino[2,3-c]pyrrol-5-yl)-4-methyl-1-piperazinecarboxylate (suriclone, RP 31264), a new anxiolytic, produced behavioral effects similar to those of diazepam and lorazepam, had a protective effect against electroshock convulsion and potentiated the sleeping effect of hexobarbital in mice. It inhibited crossed extensor reflexes in chicks and augmented the dorsal root reflex potential, the increase of which is considered to be an index of increased GABAergic presynaptic inhibition. Suriclone produced high-amplitude slow waves in the amygdala and cerebral cortex and desynchronization of theta waves in the hippocampus in rat electroencephalogram (EEG). These observations were quantitatively confirmed by power spectrum analysis of EEG. The mechanisms of action of suriclone on the CNS are discussed in relation to those of benzodiazepines. PMID- 2886130 TI - Morphine and dynorphins in lipid mobilization in rats in vitro. AB - In vitro lipid-mobilizing activities of morphine (MO) and dynorphin-(1-10) amide (DYA) were compared using adipocytes of young adult rats (body weight 170-200 g, age 50-60 days, diameter of adipocytes 54 +/- 1.12 microns) and of 20-month-old rats (body weight 500-690 g, diameter of adipocytes 99.5 +/- 3.0 microns). The adipokinetic activities of adenosine deaminase (ADA) and dynorphin-(1-13) (DY) were also tested. In the experiments 0.16 units of ADA did not influence basal or stimulated lipolysis, whereas DY exerted a slight but statistically significant adipokinetic effect. In three experimental series the EC50 of MO ranged between 0.89 and 14.60 mumol l-1, the EC50 of DYA in young rats was estimated as 0.8 mumol l-1 and in old animals, 1.3 mumol l-1. Statistically significant differences in the lipid-mobilizing potency between DYA and MO could be observed only in one experimental series in young rats. Expressed in percent of maximum lipolysis induced by isoprenaline, the maximum lipolytic response to DYA in young animals was significantly lower (Emax 26.1 +/- 1.9) when compared to the maximum effect of MO (Emax 76.3 +/- 8.5 and 68.9 +/- 3.5, respectively). Adipocytes of old rats seemed to be more sensitive not only against MO but also against DYA. When studying lipolysis no signs of competitive dualism could be observed in the interaction between MO and DYA. The possibility of two or more independent lipid mobilizing mechanisms in the effect of the two opioids compared cannot be excluded. PMID- 2886131 TI - [Hemodynamic effects of intravenously administered celiprolol in patient with coronary heart disease and depressed left ventricular function]. AB - Hemodynamic changes after intravenous application of 10 mg celiprolol-HCl (3-[3 acetyl-4-(3-tert-butylamino-2-hydroxy-propoxy)-phenyl]-1,1-diethyl urea hydrochloride. Selectol; in the following briefly called celiprolol) were investigated over an interval of 30 min in 15 patients with angiographically determined coronary heart disease and depressed left ventricular function (ejection fraction less than 60%, left ventricular end-diastolic pressure (LVEDP) greater than 12 mmHg). One patient suffered from severe left ventricular failure with lung edema and could not be evaluated. The heart rate was not influenced, the arterial pressure was significantly reduced (p less than 0.01), similarly LVEDP (p less than 0.001), and pulmonary pressure (p less than 0.01). Cardiac output and total peripheral resistance were not changed significantly. The hemodynamic working profile of celiprolol in patients with depressed left ventricular function is that of a beta 1-receptor blocker with a strong intrinsic sympathomimetic activity (ISA = Intrinsic Sympathetic Activity) and vasodilating properties--even on preload. The intravenous application of celiprolol in patients with severely depressed left ventricular function can cause pump failure. PMID- 2886132 TI - The search for a biological basis for mental illness. PMID- 2886133 TI - High-dose clonidine motor syndrome: relationship to serotonin syndrome. AB - Reciprocal forepaw treading, hindlimb abduction, and Straub tail are some of the abnormal motor behaviors of the classical 'serotonin syndrome,' which results from activation of serotonin (5-HT) receptors. However, we also observed them in the syndrome evoked by the alpha-adrenergic agonist clonidine, at high doses (5 40 mg/kg). Other features of the clonidine syndrome (scored from videotapes) were body and head tremor, forelimb hyperextension, ataxia, vertical jumping, tactile hyperreactivity, and autonomic signs (piloerection, pupillary dilatation, salivation, proptosis). The clonidine syndrome persisted for several hours and was not lethal. Clonidine suppressed locomotor activity (photocell recording) and induced episodes of catalepsy and 5-HT-independent impairment of motor habituation. Single high doses of drugs active at several different neurotransmitter receptors significantly reduced total behavioral score through effects primarily on tremor and autonomic signs, but none prevented the clonidine syndrome. Lesions of monoaminergic neurons [intracisternal 5,7 dihydroxytryptamine (DHT) or 6-hydroxydopamine] or monoamine depletion by intraperitoneal reserpine all failed to prevent this motor syndrome. Co administration of 5-HTP and clonidine did not exacerbate the clonidine syndrome in naive rats and did not prevent the onset of the serotonergic syndrome in rats with DHT lesions. These data suggest that neither catecholamines nor 5-HT have a major role in the serotonin-like behavioral responses to high doses of clonidine. PMID- 2886134 TI - Neurotransmitters and memory: role of cholinergic, serotonergic, and noradrenergic systems. AB - In Alzheimer's disease (AD), pathological changes are found in the basal forebrain cholinergic system (BFCS), serotonergic raphe (RA), and noradrenergic locus coeruleus (LC) systems. The present study was designed to determine the extent to which selective damage in each of these systems individually could produce an impairment of memory, one of the clinical symptoms of AD. Rats were given selective lesions by injecting ibotenic acid into the nucleus basalis magnocellularis and medial septal area (i.e., BFCS); 5,7-dihydroxytryptamine into the medial and dorsal RA; and 6-hydroxydopamine (6-OHDA) into the LC or by ip injections of (2-chloroethyl)N-ethyl-2-bromobenzylamine HCl (DSP4). Levels of choline acetyltransferase (ChAT), norepinephrine, and serotonin verified lesion effectiveness and selectivity. Chronic changes in serotonergic-2 and beta adrenergic receptors were also determined. Rats were tested in a delayed spatial alternation in a T-maze. BFCS lesions impaired choice accuracy with intertrial delays of 5, 30, and 60 s. RA lesions or DSP4 injections impaired choice accuracy only when the intertrial delay was 60 s. LC lesions (by 6-OHDA) did not impair choice accuracy at any delay. The results suggest that the pathological changes in the BFCS and RA are sufficient to produce the types of memory impairments associated with dementia, but the quantitative effects of pathology in these two systems are different. PMID- 2886136 TI - Studies on the organization of the human apolipoprotein B 100 gene. AB - The organization of five exons of the 3' terminal end of the human apolipoprotein B 100 (apo B 100) gene 1906, 184, 115, 7572 and 374 bp long have been determined from two overlapping EMBL3 human genomic clones extending over 18 kb. They encode more than 70% of the apo B 100 amino-acid sequence. The introns between these five exons were sequenced revealing the common intron/exon splice junction sequences. The 7572 bp exon is the longest exon so far reported for mammalian genes with the proposed sequence coding for the LDL receptor binding site. Its possible relationship to apolipoprotein B 48 is discussed. PMID- 2886135 TI - Dose- and strain-dependent effects of dermorphin and [D-Ala2-D-Leu5]enkephalin on passive avoidance behavior in mice. AB - Dermorphin and [D-Ala2-D-Leu5]enkephalin, administered intracerebroventricularly (icv) immediately after training in a passive avoidance test, exerted dose- and strain-dependent effects in DBA/2 (DBA) and C57BL/6 (C57) mice. In fact, the peptides impaired, at a low dose (5 ng), the retention performances of both strains; a higher dose (50 ng) impaired retention in DBA but improved it in C57 mice. A dose of naloxone (0.3 microgram, icv), which was ineffective when administered alone, antagonized the effects observed. The results are discussed in terms of strain differences in central mechanisms. PMID- 2886137 TI - [Immunological aspects of using plasmapheresis, leukocytapheresis and lymphocytoplasmapheresis in treating nonspecific aortoarteritis]. AB - Nine female patients with Takayasu's disease have been studied. Some changes in humoral and cellular immunity, an increase in erythrocyte sedimentation rate and a decrease in peripheral blood flow have been found. The patients were treated by plasmapheresis, lymphocytapheresis or lymphocytoplasmapheresis, the way of treatment depending on the nature of changes revealed. The treatment resulted in normalization (in some cases only a trend towards normalization was observed) of immunological data, a decrease in erythrocyte sedimentation rate and improvement of the peripheral blood flow. All the patients responded well to the treatment. PMID- 2886138 TI - [Potential clinical use of an acid-stable proteinase inhibitor from human urine]. AB - The method for the preparation of a specific proteinase adsorbent (acid-resistant human urinary proteinase inhibitor--UPI--immobilized on sepharose) has been developed. Proteinase adsorption using this adsorbent has proved highly effective in the treatment of acute pancreatitis with plasmasorption. High adsorption capacity of UPI-sepharose from plasma samples of patients with acute nonspecific aortoarteritis has been demonstrated in vitro. Determination of UPI activity in the human urine is an informative test for early tissue damage, as compared to plasma middle molecules assay. The former test may be used as a diagnostic technique in patients with parenchymal kidney injury and increased arterial pressure. PMID- 2886139 TI - Inhibition by astemizole of activity from the isolated semicircular canal. AB - Since astemizole does not readily pass the blood-brain barrier, it was surprising that it was found useful in patients with chronic vertigo. We therefore speculated that the drug may reach the inner ear and act directly on the sensory cell-afferent nerve synapse. Mice, injected with tritiated astemizole and killed 17 hours later, showed the presence of the drug in the vestibular tissues. Nerve recordings were made from the isolated posterior semicircular canal of the frog. Both spontaneous and stimulated firing rates were obtained with artificial perilymph containing astemizole bathing the isolated canal preparation. Results showed that astemizole has a significant inhibitory effect on vestibular nerve activity at concentrations of 10(-7) mol/L and higher. The exact site of astemizole's inhibitory action is undetermined but is most likely at the hair cell-afferent nerve synapse. PMID- 2886140 TI - Cartilage fucoproteins with sites for cross-linking by transglutaminase. AB - Slices of various types of cartilage were incubated with either L-[6-3H]fucose or [1,4-3H(N)]putrescine. Homogenization of the slices and fractionation of the homogenates showed for both labels that an insoluble collagenase-resistant fraction had the highest specific activity (dpm/mg dry weight). Examination of an exhaustive proteolytic digest of this insoluble fraction by ion-exchange high performance liquid chromatography showed the presence of gamma glutamyl[3H]putrescine. Chromatography of solubilized [3H]fucoprotein fractions showed the presence of several low molecular weight peaks, as well as high molecular weight material. Incubation of [3H]fucoprotein extracts with transglutaminase increased the high molecular weight peaks and decreased the low molecular weight ones. Incubation of the cartilage slices with L-[3H]fucose plus 0.5 mM dansylcadaverine, an inhibitor of transglutaminase, caused a decrease in the insoluble and high molecular weight fraction relative to the low molecular weight peaks. It is hypothesized that this is due to inhibition of cross-link formation between fucoprotein components of the cartilage which are transglutaminase substrates. One major low molecular weight peak, which labels with both fucose and putrescine, corresponds in size with the 15,000 subunit of collagen III aminopropeptide, which is known to be a substrate for transglutaminase. PMID- 2886142 TI - Effects of fasting and oral premedication on the pH and volume of gastric aspirate in children. AB - The pH and volume of gastric aspirate were measured immediately after the induction of anaesthesia in 224 healthy children to determine the effects of decreasing the period of fasting and of giving oral premedicants before anaesthesia. Fasting for less than 4 h was found to increase the volume of gastric aspirate and the risk of developing pulmonary aspiration syndrome. Trimeprazine syrup was found to increase the pH of the gastric contents, and decrease the likelihood of the pulmonary aspiration syndrome. There was a significant increase in gastric volume in patients premedicated with temazepam elixir which did not occur in patients given temazepam capsules. These results support the custom of fasting patients for at least 4 h before anaesthesia and indicate that oral premedicants and their vehicles can have significant effects on the stomach. PMID- 2886141 TI - Lipid alterations in liver and kidney induced by normobaric hyperoxia: correlations with changes in microsomal membrane fluidity. AB - The effects of normobaric hyperoxia on both microsomal membrane fluidity and mechanism of phospholipid synthesis in rabbit liver and kidney have been studied. Hyperoxia induces in both organs an impairment of de novo synthesis of glycerolipids which could be due to an inactivation of acyltransferase activities involved in the initial formation of phosphatidic acid. The ability to replace phospholipid fatty acids by reacylation mechanism decreases slightly in the hyperoxic kidney, while it does not change in the hyperoxic liver. Concerning the effect of high arterial pO2 on microsomal membrane fluidity, the hyperoxic liver shows a more fluid environment within the membrane core of microsomes; however, no difference was shown in that of microsomal membrane core of hyperoxic kidney. An insight into the lipid composition of microsomes indicates that liver microsomal membranes have lower cholesterol content and higher unsaturation degree of phospholipid fatty acids, whereas hyperoxic kidney microsomes become more saturated and did not show any difference in their cholesterol content. In both hyperoxic liver and kidney microsomes, phospholipid content decreases in agreement with the depression of phosphatidic acid biosynthesis. These results are discussed in relation to the values of microsomal membrane microviscosity obtained. PMID- 2886143 TI - Effects of H-2 antagonists on the elimination of bupivacaine. AB - The effects of two histamine H-2 antagonists, cimetidine and ranitidine, on the elimination of bupivacaine were studied in four male volunteers. The cimetidine treated group demonstrated a statistically significant decrease in clearance of bupivacaine. These results indicate that concomitant administration of cimetidine and bupivacaine may increase the likelihood of toxicity of the latter agent. PMID- 2886144 TI - Present state of extradural and intrathecal opioid analgesia in Sweden. A nationwide follow-up survey. AB - A nationwide follow-up survey was undertaken to study the use of extradural and intrathecal opioids in the management of pain, to estimate the incidence of delayed ventilatory depression and to study post-injection surveillance routines. A questionnaire was sent to all 93 anaesthetic departments in Sweden; 96% responded. The major indication for using extradural opioids was the treatment of postoperative, traumatic and cancer pain. During 1984 over 14,000 patients received extradural, and over 1100 patients intrathecal, opioids. Morphine was the predominant opioid for extradural administration and was used in 96% of patients. Extradural opioid analgesia constitutes about 25% of all extradural blocks performed in Sweden. Pruritus and urinary retention were considered as minor problems; however, the risk was considerably higher after intrathecal morphine. The incidence of delayed ventilatory depression was about 1:1100 (0.09%) following extradural morphine and 1:275 (0.36%) following intrathecal morphine. Risk factors for delayed ventilatory depression are discussed. Administration of extradural morphine for postoperative pain relief in patients undergoing major surgery is considered a high benefit-low risk technique by most Swedish anaesthetists. The results of the present nationwide survey suggests that, following extradural morphine, surveillance of patients for more than 12 h appears unnecessary. PMID- 2886145 TI - Benzodiazepine withdrawal: outcome in 50 patients. PMID- 2886146 TI - Famotidine does not affect indocyanine green disposition and serum bile acid levels in healthy subjects. PMID- 2886147 TI - Biochemical and ultrastructural alterations accompany the anti-proliferative effect of butyrate on melanoma cells. AB - The effect of sodium butyrate on mouse and human melanoma cell lines was evaluated. Sodium butyrate (0.1-2mM) is shown to reduce the clonogenic potential of several melanoma cell lines. The antiproliferative effect of sodium butyrate is accompanied by a marked increase in the activity of the plasma-membrane bound enzyme gamma-glutamyl transpeptidase. Sodium butyrate treated cells acquire a well developed rough endoplasmic reticulum and accumulate fat droplets. The development of the endoplasmic reticulum is associated with a marked increase in the activity of the enzyme marker NADPH cytochrome c reductase. It is suggested that the phenotypic alterations induced by sodium butyrate may serve as markers for the action of this agent on melanoma cells and other tumours. PMID- 2886148 TI - Dependence of the activity of beef heart mitochondrial adenosinetriphosphatase on the properties of the catalytic metal ion. AB - Several divalent metal ions were used as kinetic probes of the beef heart mitochondrial adenosinetriphosphatase (F1) under a variety of conditions, and the relationship between the properties of the catalytic metal ion and the catalytic activity of the enzyme was examined. Vmax for ATP hydrolysis was largest when metal ions characterized by intermediate values of acidity of coordinated water molecules (pKa) and metal-nucleotide stability constants (Kstab) were present. As temperature increased, the peak of Vmax vs. pKa (or Kstab) shifted to lower initial values of pKa or Kstab. The solvent deuterium isotope effect on Vmax (DV) was normal and largest when the metal ion present during F1-catalyzed ATP hydrolysis was most acidic and the metal nucleotide stability constant was large. When an active site tyrosine on F1 was nitrated, Vmax was most affected when the metal ion present was least acidic and the metal nucleotide stability constant was small. The isotope effect on V/K (DV/K) was normal, small, and apparently independent of the metal ion present. ADP inhibition of F1-catalyzed ATP hydrolysis is competitive, and the Ki is independent of the metal ion present. The degree of Pi inhibition of F1 is dependent on the metal ion present. The inhibition by Pi is competitive at low temperature and becomes noncompetitive as temperature increases. These and previous results support a mechanism whereby a water molecule coordinated to the metal ion of an enzyme-bound gamma-monodentate metal-ATP complex is deprotonated to begin a series of events whereby a beta,gamma-bidentate metal-ATP complex is produced. Upon hydrolysis, the bond between the metal ion and the beta-phosphate of ADP in the Pi-metal-ADP complex is broken before products (ADP and metal-Pi) are released. PMID- 2886149 TI - pH-dependent bilayer destabilization by an amphipathic peptide. AB - A 30-residue amphipathic peptide was designed to interact with uncharged bilayers in a pH-dependent fashion. This was achieved by a pH-induced random coil-alpha helical transition, exposing a hydrophobic face in the peptide. The repeat unit of the peptide, glutamic acid-alanine-leucine-alanine (GALA), positioned glutamic acid residues on the same face of the helix, and at pH 7.5, charge repulsion between aligned Glu destabilized the helix. A tryptophan was included at the N terminal as a fluorescence probe. The rate and extent of peptide-induced leakage of contents from large, unilamellar vesicles composed of egg phosphatidylcholine were dependent on pH. At pH 5.0 with a lipid/peptide mole ratio of 500/1, 100% leakage of vesicle contents occurred within 1 min. However, no leakage of vesicle contents occurred at pH 7.5. Circular dichroism measurements indicated that the molar ellipticity at 222 nm changed from about -4000 deg cm2 dmol-1 at pH 7.6 to 11,500 deg cm2 dmol-1 at pH 5.1, indicating a substantial increase in helical content as the pH was reduced. Changes in molar ellipticity were most significant over the same pH range where a maximum change in the extent and rate of leakage occurred. The tryptophan fluorescence emission spectra and the circular dichroism spectra of the peptide, in the presence of lipid, suggest that GALA did not associate with the bilayer at neutral pH. A change in the circular dichroism spectrum and a blue shift of the maximum of the tryptophan fluorescence emission spectra at pH 5.0, in the presence of lipid, indicated an association of GALA with the bilayer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886150 TI - Amino acid sequence of the nucleotide binding region of chloroplast coupling factor 1. AB - The labeling of chloroplast coupling factor 1 by 3'-O-(4-benzoyl)benzoyl-ATP (BzATP) was studied. When the enzyme was incubated with approximately 10 microM BzATP and 6 mM MgCl2 at pH 7.9 for approximately 20 min and passed through two Sephadex G-50 centrifuge columns, three BzATP molecules were bound per coupling factor molecule. Photolysis of radioactive enzyme-bound BzATP followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed that the BzATP bound primarily to the beta-polypeptide. If unbound BzATP was not removed by centrifuge columns prior to photolysis, significant labeling of the alpha-polypeptide also occurred. After photolysis, the BzATP-labeled enzyme was treated with trypsin, and two radioactive peptides were isolated by high performance liquid chromatography on a C18 column. The two peptides were sequenced and found to correspond to amino acids 360-378 and 393-397 of the beta polypeptide. For the sequence 360-378, two specific amino acids were found to be radioactive (Tyr-362 and Asp-369). This region of the polypeptide is highly conserved in several different species and probably corresponds to part of the nucleotide binding region of the catalytic site. In the case of amino acids 393 397, a very low level of radioactivity was found for all amino acids. The significance of this peptide for the binding of nucleotides to coupling factor 1 could not be established. PMID- 2886151 TI - Exchange and hydrolysis of tightly bound nucleotides in normal and photolabelled bovine heart mitochondrial F1-ATPase. AB - Treatment of F1 by threefold fast-column centrifugation or by single ammonium sulphate precipitation followed by fast-column centrifugation resulted in enzyme preparations containing 2.5-2.8 mol of bound nucleotides per mol of F1. Short incubations of such F1 preparations in the presence of relatively low concentrations of [14C]ATP and 2-azido[alpha-32P]ATP (100-250 microM), followed by ammonium sulphate precipitation and fast-column centrifugation, resulted in exchange of about 1 mol of the bound nucleotide per mol of F1 not affecting the total amount of bound nucleotides. Exchange of bound nucleotides with 2-azidoATP, followed by ultraviolet irradiation, results in inhibition of the enzyme activity, full inhibition being obtained (via extrapolation) when 1 mol of 2 nitreno-adenosine 5'-tri- or diphosphate (2-N-AT(D)P) is covalently bound to the presumably catalytic site on the enzyme (Van Dongen, M.B.M., De Geus, J.P., Korver, T., Harton, A.F. and Berden, J.A. (1986) Biochim. Biophys. Acta 850, 359 368). In agreement with this, it was found that incorporated [gamma-32P]ATP was hydrolysed by more than 80%. Newly incorporated, not covalently bound radioactive nucleotides could be rapidly exchanged again by the addition of non-radioactive nucleotides, but a higher concentration of nucleotides was needed to fully exchange the incorporated nucleotide. Also, when F1 was depleted of most of its bound nucleotides by repeated ammonium sulphate precipitation, part of the residual nucleotides was still rapidly exchangeable. The ability of F1 to exchange (and hydrolyse) one of the bound nucleotides was not lost when one catalytic and one non-catalytic binding site were occupied by covalently bound 8 N-ATP. Similar results were obtained with F1 containing 2-nitrenoATP covalently bound to one of the catalytic sites. Also, after photolabelling of up to four binding sites with 8-N[( 2-3H]AT(D)P, part of the two remaining non-covalently bound nucleotides could still be rapidly exchanged. In this case the exchanged nucleotide was also hydrolysed. It is concluded that one of the two bound nucleotides became exchangeable when all four other sites (i.e., two catalytic and two non-catalytic) were occupied with covalently bound nucleotides. The site involved showed catalytic properties suggestive of localisation on a beta subunit. PMID- 2886152 TI - Targeting of anti-Thy 1.1 monoclonal antibody conjugated liposomes in Thy 1.1 mice after intravenous administration. AB - 125I-labeled liposomes, conjugated to an anti-Thy 1.1 monoclonal antibody (MRCOX7), demonstrated up to 7.4-fold greater lymph node uptake than liposomes conjugated to non-specific monoclonal antibody (R-10) after intravenous injection into Thy 1.1 (AKR-J) mice. Uptake of anti-Thy 1.1-conjugated liposomes by the lymph nodes of AKR-J mice was 3-times greater than their uptake by lymph nodes of Thy 1.2 (AKR-Cu) mice. Lymph node localization of anti-Thy 1.1-liposomes was equal to that of control monoclonal antibody-liposomes in Thy 1.2 mice. Conjugation to either monoclonal antibody substantially increased liposome clearance by the liver, while decreasing liposome uptake in a number of organs outside the reticuloendothelial system. Changes in liposome size and phospholipid composition did not significantly alter these results. Administration of a large predose of unconjugated liposomes prior to injection of MRCOX7-conjugated liposomes increased blood levels and reduced liver uptake of the monoclonal antibody-liposome conjugates, but did not further enhance lymph node uptake. This study demonstrates that targeting of liposomes by conjugation to the appropriate monoclonal antibody, can significantly increase their uptake in lymph nodes which contain high levels of cells expressing the target antigen. However, conjugation to monoclonal antibody also increases clearance of liposomes by the liver. To increase the uptake of monoclonal antibody-conjugated liposomes in target tissue, substantial reduction of their clearance by the reticuloendothelial system will be required. PMID- 2886153 TI - Free fatty acid uptake is increased in doxorubicin-resistant rat glioblastoma cells. AB - We have investigated the mechanism by which the rat glioblastoma C6 cell line resistant to doxorubicin presented an increase of free fatty acid utilization from the nutrient source as compared to the wild sensitive strain. We have shown that this was not due to an accelerated turnover of the phospholipid hydrophobic or hydrophilic moieties, but to an important increase of the uptake of the free fatty acids. This was demonstrated by studies performed with linoleic and linolenic acids during very short incubations, at low temperatures, and in the absence of albumin in the medium. This enhancement of free fatty acid uptake may explain the differences which exist in the acyl group composition of membrane lipids between doxorubicin-sensitive and -resistant C6 cells, because of the suppression of the essential fatty acid-deficient status of the cells. PMID- 2886154 TI - Effects of clofibric acid and tiadenol on cytosolic long-chain acyl-CoA hydrolase and peroxisomal beta-oxidation in liver and extrahepatic tissues of rats. AB - The effects of two peroxisome proliferators, p-chlorophenoxyisobutyric acid (clofibric acid) and 2,2'-(decamethylenedithio)diethanol (tiadenol), on cytosolic long-chain acyl-CoA hydrolase and peroxisomal beta-oxidation were studied in several organs of rat. Among organs of control rats, the brain had the highest activity of long-chain acyl-CoA hydrolase, followed by testis, and a low activity was found in other tissues. Administration of the peroxisome proliferators caused a marked increase in activity of long-chain acyl-CoA hydrolase in both liver and intestinal mucosa and a slight increase in the activity in kidney, but little affected acyl-CoA hydrolase activity in either brain, testis, heart, spleen and skeletal muscle. In accordance with the change in the activity of acyl-CoA hydrolase, the activity of peroxisomal beta-oxidation was markedly increased in liver, intestinal mucosa and kidney, and a slight increase was found in brain and testis, whereas peroxisome proliferators little affected the activity in other organs tested. Gel filtration of cytosol from intestinal mucosa showed that clofibric acid caused an appearance of a new peak in intestinal mucosa. Although cytosol of liver, intestinal mucosa, brain and testis contained two 4-nitrophenyl acetate esterases with different molecular weights (about 105,000 and about 55,000), these esterases are different from cytosolic long-chain acyl-CoA hydrolases of these four organs in respect of molecular weight. The administration of clofibric acid little affected cytosolic 4-nitrophenyl acetate esterases. Comparative studies on cytosolic long-chain acyl-CoA hydrolases from these four organs showed that liver hydrolase I (molecular weight of about 80,000) had properties similar to those of brain and testis enzymes. On the other hand, intestinal mucosa enzyme was different from either hepatic hydrolase I or II (molecular weight of about 40,000). The results from the present study suggest that inductions of peroxisomal beta-oxidation and cytosolic long-chain acyl-CoA hydrolases are essential responses of rats to peroxisome proliferators not only in liver but also in intestinal mucosa and that induced hydrolases are not attributable to non-specific esterases. PMID- 2886155 TI - Hepatic tyrosine aminotransferase from the rainbow lizard Agama agama: purification and some properties. AB - Tyrosine aminotransferase, induced by dexamethasone in the liver of the rainbow lizard, Agama agama, was extracted under optimal conditions which yield the native undegraded enzyme; purified by heat treatment at 65 degrees C, ammonium sulfate precipitation, chromatography on DEAE-Sephacel and Sephadex G-150-120 and then characterized. The enzyme was purified over 2000-fold to a specific activity of 2653 units/mg of protein. It had an optimum pH of 7.6 in potassium phosphate buffer, KmTyr: 1.0 mM; K alpha-KGm: 0.32 mM; Vmax: 1.33 nmol/min and a molecular weight of about 130,000. It was inhibited by L-glutamate (competitively, Ki, 2.5 mM), and by metal ions Ca2+, Mn2+, Zn2+, Hg2+ and Ag2+, but was unaffected by chelating agents and other divalent cations. Lizard hepatic cytosolic tyrosine aminotransferase was specific for L-tyrosine and alpha-ketoglutarate as substrates sensitive to sulfhydryl inactivation and to protection from thermal lability by alpha-ketoglutarate and pyridoxal phosphate. PMID- 2886157 TI - Neuroleptic malignant syndrome: review and analysis of 115 cases. AB - Neuroleptic malignant syndrome is a potentially fatal consequence of neuroleptic use that has recently gained wide attention. In this article the authors critically review the previous literature and analyze all case reports in the English-language literature (115 cases) for 43 variables. The results are discussed in light of prior literature, and recommendations are made for future research. PMID- 2886156 TI - Rat placentae gamma-glutamyltransferase activity changes during pregnancy. AB - gamma-Glutamyltransferase (D-gamma-glutamyl transpeptidase, EC 2.3.2.2) activity in rat placentae changes during gestation. The enzyme activity reaches a peak during the second trimester on a per gram of tissue basis and coincides with the greatest placental growth (hyperplasia) period. However, the enzyme activity on a per placenta basis shows two peak activity periods. One coincides with the peak of activity determined on a per gram basis. The second peak occurs in the third trimester and appears to coincide with the period of greatest fetal growth. The occurrence of these enzyme changes supports the concept of a developmental role for gamma-glutamyltransferase in providing amino acids from glutathione to the placenta and fetus. PMID- 2886159 TI - [Are the antipsychotic and side-effects of neuroleptics imperfectly known?]. AB - The influence of neuroleptics on central dopaminergic receptors is anatomically quite non-specific. Neuroleptics also have numerous pharmacological actions other than on dopamine. Taken together, these effects only explain some of the adverse reactions or drug interactions of neuroleptics and predict very poorly the treatment efficacy in given patients. PMID- 2886158 TI - Adduct formation between soluble fibrin monomers and elastin. AB - Monomers of fibrin generated from fibrinogen by thrombin reacted with elastin to give a new addition product or adduct. The adduct formation results from a covalent bond between both proteins, formation of which is dependent on elastin, fibrinogen and Ca2+ concentrations; but, Factor XIIIa did not intervene. Addition of fibronectin, together with fibrinogen, as cold insoluble proteins from human plasma, and of soluble collagen from rat tail tendon did not inhibit the first reaction. This enabled us to elaborate a new artificial connective matrix. PMID- 2886160 TI - Antipsychotic drugs: current use and future prospects. AB - A wide range of antipsychotic drugs is available. This paper reviews the profile of action of such drugs, the rationale for their use, and current prescribing practice. The treatment of psychotic illness in the future, with drugs, may be possible without causing unwanted movement disorder. PMID- 2886161 TI - A colony assay for in vitro transformation by human T cell leukemia viruses type I and type II. AB - We report here the development of a rapid and quantitative method for measuring in vitro T cell transformation by human T cell leukemia viruses type I (HTLV-I) and type II (HTLV-II). This method is based on our finding that cocultivation of lethally irradiated HTLV-producing cells with peripheral blood lymphocytes (PBLs) preactivated for 24 hours with phytohemagglutinin and interleukin-2 (IL-2) induces colony formation in methylcellulose-containing medium. Colonies of about 200 cells can be clearly distinguished from background aggregates within four to six days after cocultivation. These colonies gradually increase in size and reach 300 to 1,000 cells within 14 days after cocultivation. Cells of these colonies were infected, as evidenced by expression of viral p19 antigen and the presence of HTLV proviral sequences. These cells proved to be transformed in terms of IL-2 independent continuous growth in liquid medium. Colony formation was found to depend in a linear fashion upon the percentage of the infected cells present in the irradiated cell population and is sufficiently sensitive to detect as few as 1% of virus-producing cells. PMID- 2886162 TI - Detection of HIV antigen and specific antibodies to HIV core and envelope proteins in sera of patients with HIV infection. AB - The sera of well-characterized populations were examined for three markers of human immunodeficiency virus (HIV) infection; HIV antigen (HIV Ag), and antibodies to HIV envelope (gp41) and core (p24) proteins. Of 563 serum samples tested, 251 were from HIV-infected patients diagnosed as having AIDS manifested by opportunistic infections (AIDS-OI), AIDS-associated Kaposi's sarcoma (AIDS KS), or AIDS-related complex (ARC). One hundred seventy-six specimens tested were from asymptomatic high-risk individuals, and 136 were from heterosexual control subjects or patients with non-AIDS-related disease. None of the 136 control individuals tested had HIV Ag or HIV antibodies to either p24 or gp41. Of the 427 HIV-seropositive individuals, 99% to 100% were positive for gp41 antibodies to HIV. In contrast, the seroprevalence of p24 antibodies to HIV varied from 23% to 83% and appeared to be inversely associated with the severity of the patients' clinical symptoms. When specimens were analyzed for the presence of HIV Ag, in seropositive individuals the prevalence rate for this marker was lowest (1.4%) in asymptomatic individuals and highest (50%) in the AIDS-OI diagnosed group. Also, 240 cases with AIDS-KS, AIDS-OI, and ARC and the group of asymptomatic high-risk individuals were analyzed for T helper/T lymphocytes (T4) cell number and T4/T8 ratio; only one (2.0%) HIV Ag-positive case showed a T4 cell number greater than 400 and a normal T4/T8 ratio. These studies appear to demonstrate a direct correlation between the presence of HIV Ag and the severity of clinical complications of HIV infection. PMID- 2886163 TI - Use of immobilized exopeptidases and volatile buffers for analysis of peptides by fast atom bombardment mass spectrometry. AB - beta-Lipotrophin (62-77) or Ac-gastrin releasing peptide was incubated with immobilized carboxypeptidase Y or aminopeptidase M. Subsequent aliquots of each incubation mixture were analysed by fast atom bombardment mass spectrometry using a dithiothreitol/dithioerythritol liquid matrix. The use of immobilized enzymes and volatile buffers for exopeptidase digestions enabled rapid and facile separation of enzyme from digestion products. This approach to mass spectral peptide analysis reduced spectral background arising from a glycerol matrix, buffer salts, or enzyme proteins and contaminants, enabling analysis of as little as 200 picomoles of a suitable peptide. PMID- 2886164 TI - Quantitative analysis of S3341 in human plasma and urine by combined gas chromatography-negative ion chemical ionization mass spectrometry: 15 month inter day precision and accuracy validation. AB - A new quantitative assay for the determination of S3341, an alpha-2 agonist antihypertensive drug, has been developed using combined gas chromatography negative ion chemical ionization mass spectrometry. The [M]-. ions from TFA derivatives of S3341 (m/z 276) and the internal standard (2H4)S3341 (m/z 280) are monitored simultaneously by selected ion monitoring. For S3341 concentrations ranging from the limit of detection (0.2 ng ml-1 using 1 ml of plasma) to 5 ng ml 1, the average assay precision (CV) is approximately 7% while the average assay accuracy (percentage of error) is 4%. Validation of the day-to-day precision and accuracy was realized after analysing control plasma samples (n = 295) concurrently with the biological samples collected during the pharmacokinetic studies conducted over 15 months. The average day-to-day precision (CV) and accuracy (percentage of error) are 10% and 6% respectively, thus indicating that this assay procedure routinely provides reliable analytical data. PMID- 2886165 TI - Evidence for two mechanisms of human erythrocyte endocytosis by Entamoeba histolytica-like amoebae (Laredo strain). AB - A study of the ultrastructural aspects of endocytosis of human erythrocytes by Entamoeba histolytica-like amoebae (Laredo) revealed two different mechanisms of endocytosis. First, there is classical phagocytosis which consists of the formation of a phagocytotic pseudopod. This process begins with the engulfment of the red blood cell followed by its entrapment in a food vacuole of the same size as the erythrocyte. It is then digested in the food vacuole. The second means of endocytosis is achieved through a preliminary lytic attack on the red blood cell. Following attachment of the prey to the attacking cell, dendritic extensions elongate from the surface of the amoeba at the site of attachment. Intense folding and liquefaction of the red blood cell membrane is then observed. The fluid membrane is then sucked into the amoeba through a pinocytotic-like channel. The end result is the formation of small vacuoles in the amoeba's cytoplasm, filled with the digested red blood cell. PMID- 2886166 TI - Muscarinic agonists block five different potassium conductances in guinea-pig sympathetic neurones. AB - Muscarinic excitation of sympathetic ganglion cells has usually been thought to result from inhibition of an outward K+ current, the M current, although in other neurones several conductances have been shown to be blocked by muscarinic agonists. We report that, as well as resting K+ conductance, all of four different K+ conductances, two voltage-dependent (M currents and A currents) and two calcium-dependent (responsible for slow and very slow afterhyperpolarizations), present in different sub-types of guinea-pig sympathetic neurones, are inhibited by the muscarinic agonists, bethanechol and muscarine. All of these effects increase neurone excitability and can lead to repetitive discharge. PMID- 2886167 TI - D2-dopamine receptor-mediated inhibition of intracellular Ca2+ mobilization and release of acetylcholine from guinea-pig neostriatal slices. AB - The effect of dopamine receptor activation on electrically- or high K+ (30 mM) evoked neurotransmitter release and rise in intracellular Ca2+ concentration was investigated using slices of guinea-pig neostriatum. A specific D2-dopamine receptor agonist, LY-171555 (a laevorotatory enantiomer of LY-141865: N-propyl tricyclic pyrazole) at 10(-6) M inhibited electrical stimulation- and high K+ evoked release of [3H]-acetylcholine ([3H]-ACh) to 47.7 +/- 6.0% and 54.1 +/- 5.0% of control, respectively. The maximal inhibition by LY-171555 at 10(-5) M was 54.8 +/- 5.1% reduction of the control. The half-maximal effective concentration (EC50) of LY-171555 for the inhibition of [3H]-ACh release was 2.3 X 10(-7) M. A specific D2-dopamine receptor antagonist, (-)-sulpiride (10(-7) M) reversed the inhibition of [3H]-ACh release induced by LY-171555. A specific D1 dopamine receptor agonist, SK&F 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl 1H-benzazepine) (10(-5) M) had no effect on the release of [3H]-ACh. LY-171555 (10(-6) M) also inhibited the high K+-evoked endogenous glutamate release, by 47% of control. This inhibitory effect was reversed by (-)-sulpiride (10(-7) M). We used a fluorescent, highly selective Ca2+ indicator, 'quin 2' to measure intracellular free Ca2+ concentrations ([Ca2+]i). Electrical stimulation of slices preloaded with quin 2 led to an elevation of relative fluorescence intensity and this response was reduced by the removal of Ca2+ from the bathing medium. These results indicate that the enhanced elevation in fluorescence intensity in the quin 2-loaded slices reflects the increase of intracellular free Ca2+ concentration, [Ca2+]i. The mixed D1- and D2-receptor agonist, apomorphine and LY-171555 inhibited the increase of [Ca2+]i induced by electrical stimulation or high K+ medium, in a concentration-dependent manner, while SK&F 38393 did not affect the increase of [Ca2+]i. The maximal inhibitory effect of LY-171555 at 3 X 10(-5) M was 35 +/- 3% reduction in control values. The inhibitory effect of LY 171555 was antagonized by (-)-sulpiride (10(-7) M). There was a high correlation (r = 0.997, P less than 0.05) between the D 2-receptor-mediated inhibition of the stimulated rise of [Ca2+]i and [3H]-ACh release. When the slices were superfused with the Ca2+-free medium containing EGTA (10(-4) M) for 5 min, the rise in [Ca2+]i was markedly suppressed to 18.0% of control by LY-171555 (10(-6) M). These data indicate that activation of the D2-dopamine receptor suppresses the elevation of [Ca2+]i induced by depolarizing stimuli. This may be due to inhibition of mobilization of Ca2+ from the intracellullar store. We propose that the D2-receptor-mediated inhibition of transmitter release is probably due to a reduction in intracellular Ca2+ mobilization. PMID- 2886168 TI - Blockade by nifedipine of responses to intravenous bolus injection or infusion of alpha 1- and alpha 2-adrenoceptor agonists in the pithed rat. AB - Nifedipine was tested against pressor responses in the pithed rat to ten agonists with varying selectivity for alpha 1- and alpha 2-adrenoceptors, injected as a bolus or infused intravenously: i.e. amidephrine, azepexole, cirazoline, indanidine, M7, methoxamine, noradrenaline (NA), oxymetazoline, phenylephrine and xylazine. Nifedipine, administered before the agonists, inhibited responses initiated by all agonists, usually for both the bolus and infusion responses. With a bolus, blockade was significantly greater against the more prolonged, secondary components of the pressor responses. This demonstrates that calcium entry occurs during the secondary component of the alpha-adrenoceptor-mediated response and can be initiated by either alpha 1- or alpha 2-adrenoceptor subtypes. The time courses of responses to infusion varied. Selective alpha 1 adrenoceptor agonists, with the exception of indanidine, did not produce a stable pressor response during the 20 min infusion time but alpha 2-adrenoceptor agonists did. Nifedipine reduced responses to infusion with no preference for alpha 1- or alpha 2-agonists. Phenylephrine and NA produced pressor responses which reached a peak and then declined during the remainder of the infusion. The levels of NA in arterial and venous plasma were measured by h.p.l.c. during the infusion of NA. Arterial NA levels rose throughout the infusion whereas venous levels remained relatively unaffected. The absolute levels of plasma NA suggest that a large proportion of intravenously administered NA is removed in the pulmonary circulation and the remainder is removed in the systemic circulation with negligible recirculation. The consequences of these results, for assessment of the mechanisms of action of adrenoceptor agonists and calcium entry blockers, are discussed. PMID- 2886169 TI - Stimulation of alpha 1-adrenoceptors in rat kidney mediates increased inositol phospholipid hydrolysis. AB - The molecular events which follow activation of alpha 1-adrenoceptors in rat kidney were investigated by measuring inositol phospholipid hydrolysis. Slices were labelled with [3H]-inositol (0.25 microM) and the accumulation of [3H] inositol phosphates ([3H]-IP's) was measured after stimulation with alpha adrenoceptor agonists. Phospholipid labelling was both time- and Ca2+-dependent. In kidney, Ca2+ (1 mM) increased the incorporation of [3H]-inositol by 49% and in cerebral cortex reduced it by 46%. Following addition of noradrenaline (NA, 1 mM), accumulation of [3H]-IP's increased linearly for at least 60 min. In Ca2+ free buffers a 2.1 fold increase in [3H]-IP accumulation was observed and further increases in stimulated and control levels were produced in the presence of Ca2+ (2.5 mM). These responses were attenuated by the inclusion of indomethacin (10 microM) and abolished in the presence of EGTA (0.5 mM). Responses to (-)-NA were more than 4 fold higher in the renal cortex than in the medulla. Separation of the IP's which accumulate after alpha-adrenoceptor agonists showed that after 60 min stimulation the major products were glycerophosphoinositol and inositol phosphate with smaller amounts of inositol-bisphosphate and inositol trisphosphate. The most effective agonists tested for stimulation of accumulation of [3H]-IP's were (-)-NA greater than phenylephrine greater than methoxamine, (+) NA. Clonidine and (-)-isoprenaline were ineffective at concentrations up to 100 microM. The order of effectiveness of alpha-adrenoceptor antagonists was prazosin greater than BE2254 greater than phentolamine greater than idazoxan greater than rauwolscine. The results indicate that alpha 1-adrenoceptors in rat kidney are linked to phosphoinositide hydrolysis and that this response is localized mainly to the renal cortex. PMID- 2886170 TI - The novel anticonvulsant MK-801 binds to the activated state of the N-methyl-D aspartate receptor in rat brain. AB - The influence of endogenous and exogenous acidic amino acids on the binding of [3H]-MK-801, a selective, non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, has been investigated in rat cerebral cortex crude synaptic membranes (CSM). Removal of endogenous glutamate and aspartate from CSM by repeated washing reduced the affinity of [3H]-MK-801 for its binding site (with no change in the total number of binding sites) and increased NMDA-sensitive L [3H]-glutamate binding. In washed CSM, competitive NMDA antagonists of the DL alpha-amino-omega-phosphonocarboxylate series reduced [3H]-MK-801 binding and NMDA-sensitive L-[3H]-glutamate binding, the most active compounds being 2-amino 5-phosphonovalerate (AP5) and 2-amino-7-phosphono-heptanoate (AP7). Exogenous excitatory amino acid agonists enhanced the binding of [3H]-MK-801 to washed CSM by up to 700%. A selective involvement of NMDA receptors in these effects was indicated by the excellent correlation between EC50s for stimulation of [3H]-MK 801 binding and IC50s for inhibition of NMDA-sensitive L-[3H]-glutamate binding in the same membranes. The selective, competitive NMDA receptor antagonist D-AP5 blocked the L-glutamate-induced increase in [3H]-MK-801 binding in a competitive manner with a pA2 value of 6.0. These results seem to reflect a molecular interaction between two distinct components of the NMDA receptor complex: the transmitter recognition site and the site through which MK-801 exerts its antagonist effects, possibly the ion channel. PMID- 2886172 TI - Difference in the potency of alpha 2-adrenoceptor agonists and antagonists between the pithed rabbit and rat. AB - The subtypes of alpha-adrenoceptors which mediate pressor responses to sympathomimetic agonists or to nerve stimulation in pithed rabbits have been classified according to the effects of 'selective' antagonists and a comparison has been made, for the alpha 2-subtype, with corresponding responses in the rat. In the rabbit the dose-response curve for phenylephrine was shifted to the right in parallel by prazosin (1 mg kg-1) and was unaffected by rauwolscine (1 mg kg 1). The dose-response curve for noradrenaline was shifted to the right by prazosin (1 mg kg-1) and was shifted to a smaller extent by rauwolscine (1 mg kg 1) or imiloxan (10 mg kg-1). After rauwolscine, prazosin produced a rightward shift larger than when given alone. After prazosin, rauwolscine produced a rightward shift larger than when given alone. The responses to pressor nerve stimulation at low frequencies (less than 1 Hz) could be reduced by prazosin, rauwolscine or imiloxan but those at a higher frequency could be reduced only by prazosin. These results indicate that the responses to noradrenaline or to nerve stimulation are mediated by both alpha 1- and alpha 2-adrenoceptors. Low doses or frequencies have a proportionately greater component which is alpha 2. Responses to noradrenaline after prazosin (1 mg kg-1), were sufficiently sensitive to rauwolscine to be considered as predominantly alpha 2. A comparison was therefore made of such responses in the rat and rabbit. They were produced by a lower dose per unit body weight in the rat whereas this was less marked for the alpha 2 adrenoceptor agonist guanabenz. In the rabbit they were more susceptible to blockade by rauwolscine but were less sensitive to Wy 26703 than in the rat. This demonstrates that the alpha 2-adrenoceptors mediating pressor responses in vivo, like those in other tissues in vitro, are different in rat and rabbit, with regard to antagonists. PMID- 2886171 TI - Effects of nipradilol on myocardial ischaemia produced by coronary stenosis in dogs. AB - Effects of nipradilol which is a new beta-adrenoceptor blocking agent endowed with nitroglycerin-like vasodilator actions, its denitrated derivative (denitro nipradilol) and propranolol on abnormalities of regional myocardial shortening produced by partial occlusion of the left circumflex coronary artery (LCX) were studied in anaesthetized open-chest dogs. In the presence of LCX stenosis, nipradilol (0.1 mg kg-1, i.v.) produced marked decreases in heart rate and LVdP/dt without a significant increase in left ventricular end-diastolic pressure (LVEDP). It improved impaired myocardial segment shortening and restored normal cardiac lactate metabolism. Denitro nipradilol (0.2 mg kg-1 i.v.) and propranolol (0.2 mg kg-1 i.v.) both caused similar haemodynamic changes to nipradilol but also produced a significant increase in LVEDP. However, improvement by these two agents of regional dysfunction in the ischaemic myocardium was comparable to those seen with nipradilol. All three agents markedly inhibited isoprenaline induced tachycardia, but vehicle did not. Atrial pacing abolished the beneficial effect of nipradilol on myocardial shortening in the ischaemic region without affecting other haemodynamic parameters. These results indicate that nipradilol alleviates acute myocardial ischaemia produced by coronary stenosis with similar efficacy to denitro nipradilol and propranolol suggesting, that a major part of the beneficial effect of nipradilol may be attributable to its beta-adrenoceptor blocking action. PMID- 2886173 TI - Failure of enhancement by labetalol of bronchopulmonary effects of histamine in guinea-pigs: independence of alpha-adrenoceptor antagonism. AB - The effect of labetalol on histamine-induced bronchoconstriction was studied in anaesthetized guinea-pigs. Unlike propranolol (1 mg kg-1), the same dose of labetalol did not enhance histamine-induced bronchoconstriction. To determine whether the absence of enhancement of the respiratory effects of histamine by labetalol was due to its alpha 1-blocking properties or to its partial agonist activity at beta 2-adrenoceptors, the effects of propranolol plus prazosin and of propranolol plus labetalol on histamine-induced bronchoconstriction were examined. In both cases, the bronchoconstrictor effects of histamine were enhanced to the same extent as with propranolol alone. These data support the hypothesis that the non impairment of respiratory mechanics by labetalol is not due to antagonism at alpha-adrenoceptors and may be mediated by its partial agonist activity at beta 2-adrenoceptors. PMID- 2886176 TI - Combination chemotherapy in rheumatoid arthritis. PMID- 2886175 TI - A response to isoprenaline unrelated to alpha- and beta-adrenoceptor agonism. AB - The hypothesis that beta-adrenoceptor agonism might explain a reported lack of competitive antagonism between alpha 2-adrenoceptor antagonists and agonists of the phenylethylamine class was tested in the electrically field stimulated ileum of the guinea-pig. The beta-adrenoceptor agonist, isoprenaline, was used as the phenylethylamine and inhibition of 'twitch' response evoked by cholinergic stimulation was measured. In the presence of idazoxan (3 microM), to block inhibitory alpha 2-adrenoceptors, propranolol (0.1 to 5.0 microM) failed to act competitively toward isoprenaline. Isoprenaline responses totally resistant to inhibition by propranolol were obtained. As inhibitory alpha 1-adrenoceptors are absent from guinea-pig ileum, a recognition site distinct from the currently defined alpha- and beta-adrenoceptors is postulated. Agonism by phenylethylamine based agonists at this site may explain their inability to act competitively with alpha- and beta-adrenoceptor antagonists. PMID- 2886174 TI - Influence of the dopamine receptor agonists fenoldopam and quinpirole in the rat superior mesenteric vascular bed. AB - The effect of local administration of the dopamine 2 (DA2)-receptor agonist quinpirole and of the DA1-receptor agonist fenoldopam was studied in the in situ, constant flow autoperfused, superior mesenteric vascular bed of the rat. Local infusion of quinpirole (30 micrograms kg-1 min-1 for 5 min) had no effect on baseline perfusion pressure; it reduced the pressor responses to electrical stimulation (4 Hz, 1 ms, supramaximal voltage) of the periarterial sympathetic nerves to 45.6 +/- 2.1% of its original value but did not modify similar pressor responses produced by locally administered noradrenaline. The inhibitory effect of quinpirole was antagonized by the selective DA2-receptor antagonist domperidone (10 micrograms kg-1) but not by the selective DA1-receptor antagonist SCH 23390 (50 micrograms kg-1). Local infusion of fenoldopam (30 micrograms kg-1 min-1 for 5 min) reduced baseline perfusion pressure to 89.9 +/- 1.9%, increased the pressor response to electrical stimulation (4 Hz, 1 ms, supramaximal voltage) of the periarterial nerves to 134.7 +/- 14.0%, but reduced the pressor response to locally administered noradrenaline to 37.2 +/- 8.2%. Similar pressor responses induced by the selective alpha 1-adrenoceptor agonist phenylephrine were also reduced by fenoldopam (to 38.4 +/- 6.4%), but responses to locally administered angiotensin II were not modified. Pretreatment with SCH 23390 (50 micrograms kg 1) antagonized the effect of fenoldopam on baseline perfusion pressure, but had no influence on the effect of fenoldopam on responses to electrical stimulation or to noradrenaline. Pretreatment with the selective alpha 2-adrenoceptor antagonist rauwolscine (100 micrograms kg-1) had no effect on the reduction in baseline perfusion pressure induced by fenoldopam nor on its inhibitory effect on the response to noradrenaline, but it antagonized the stimulatory effect of fenoldopam on the response to electrical stimulation. 7 The results show that quinpirole inhibits neurogenic vasoconstriction in the rat superior mesenteric vascular bed through stimulation of presynaptic DA2-receptors while fenoldopam stimulates postsynaptic vasodilatory DA,-receptors. In addition, our results suggest that the inhibitory effect of fenoldopam on the vasoconstrictor response to noradrenaline may be due to an antagonistic action at postsynaptic alpha adrenoceptors, while its potentiating effect on neurogenic vasoconstriction is due to blockade of presynaptic alpha 2-adrenoceptors. PMID- 2886177 TI - Combination therapy in rheumatoid arthritis--study design. PMID- 2886178 TI - Sulphasalazine in rheumatoid arthritis: pointers to a gut-mediated immune effect. PMID- 2886180 TI - Selective loss of subpopulations of ventral mesencephalic dopaminergic neurons in the monkey following exposure to MPTP. AB - Tyrosine hydroxylase immunohistochemical examination of the mesencephalon of severely parkinsonian MPTP-treated macaque fascicularis monkeys revealed a marked loss of substantia nigra pars compacta (SNc) neurons in both medial and central portions of the nucleus with a relative sparing of neurons in the dorsal-most portions of the substantia nigra. These animals also sustained 20-65% loss of neurons in the substantia nigra pars lateralis area, ventral tegmental area (A 10), and the retrorubral area (A-8 cell group, and the parabrachialis pigmentosus region). These animals all had extreme striatal dopamine depletions. A monkey which received several small doses of MPTP and yet remained asymptomatic for a motor disorder (although it had demonstrable behavioral performance deficits) had only a loss of ventral SNc neurons, with no appreciable cell loss in associated ventral mesencephalic dopamine areas and no loss of striatal dopamine. These data suggest that the effects of MPTP are not as selective as originally thought and, more importantly, indicate that MPTP-induced parkinsonism in the primate may be more analogous to idiopathic Parkinson's disease, where cells other than SNc cells are affected. Furthermore, the present findings suggest that only certain mesencephalic dopamine neurons are susceptible to MPTP-induced damage. The unique characteristics of these neurons need to be elucidated. PMID- 2886179 TI - Single cell quantitative immunocytochemistry of cyclic GMP in the superior cervical ganglion of the rat. AB - In the superior cervical ganglion of the rat, using a newly developed antiserum against formaldehyde-fixed 3',5'-cyclic guanosine monophosphate (cGMP), cGMP immunoreactivity was observed in the large postganglionic neuronal cell bodies; no cGMP-immunofluorescence was found in nuclei or in satellite cells, glia or fibroblasts. In vitro incubation of ganglia in media with high K+ (up to 100 mM) or carbachol (10(-8)-10(-5) M) showed an increase only in cGMP-immunofluorescence in the large postganglionic cell bodies. The intensity of the immunofluorescence was taken as a measure for cGMP-immunoreactivity and was quantitated using a Leitz MPV-II system. Dose-response curves were constructed for the increase in cGMP-immunofluorescence intensity for K+ and carbachol. The carbachol stimulated cGMP-immunofluorescence intensity was antagonized competitively by atropine, whereas the high K+ stimulated cGMP-immunofluorescence intensity was not. Hexamethonium (10(-6) M) was without effect on the carbachol stimulated cGMP immunofluorescence intensity. The morphological and pharmacological data indicate that we developed a very specific procedure for quantitative immunocytochemistry of cGMP in tissue sections. This technique makes it possible to use cGMP immunofluorescence intensity as a postsynaptic parameter in individual cell bodies in heterogeneous tissue. PMID- 2886181 TI - Bilateral intranigral microinjection of morphine and opioid peptides produces antinociception in rats. AB - Bilateral intranigral microinjection of morphine produced dose-related and naloxone-reversible antinociceptive effects on the tail-flick and hot-plate tests. Intranigral injection of enkephalin had antinociceptive effects on both tests, and dynorphin had an antinociceptive effect on the hot-plate test. This is the first report of evidence that nigral opiate receptors may mediate antinociception. PMID- 2886183 TI - Evidence for a direct action of N-methylaspartate on non-neuronal cells. AB - The effects of N-methylaspartate (NMA) on extracellular amino acids and purine catabolites in the hippocampus were studied with brain dialysis in rats with unilateral hippocampal NMA lesions. In the lesioned side, an increased basal output of glutamine was observed while glutamate was significantly decreased. NMA evoked a drop in extracellular glutamine. The effect was not observed in the lesioned hippocampus. NMA markedly enhanced the release of taurine and phosphoethanolamine (PEA). This response was unchanged in NMA-lesioned hippocampus. Analysis of the tissue content of endogenous amino acids revealed decrements in glutamate and GABA whereas other amino acids were not significantly altered. The resting and NMA-stimulated efflux of inosine was higher in the intact hippocampus. However, the extracellular concentrations of the inosine break-down products hypoxanthine and xanthine were not influenced by a prior NMA lesion, neither before nor after NMA administration. The present findings indicate that NMA releases amino acids (mainly taurine and PEA) from non-neuronal cells. The depression of extracellular glutamine elicited by NMA is probably a neuronal event. A direct stimulation of the energy metabolism of non-neuronal cells by NMA appears to exist as measured by the efflux of purine catabolites. I propose that non-neuronal cells, possibly glia, possess NMA receptors which, upon stimulation, initiate biochemical changes. The physiological significance of these responses remains to be elucidated. PMID- 2886182 TI - The effect of amphetamine on the in vivo release of dopamine, somatostatin and neuropeptide Y from rat caudate nucleus. AB - Somatostatin, neuropeptide Y and dopamine release from the conscious rat caudate nucleus were investigated using the push-pull perfusion method. Significant reductions in somatostatin and neuropeptide Y release coincided with increased dopamine release, suggesting that dopamine has an inhibitory effect on the release of both peptides. Changes in the levels of both peptides were positively correlated, consistent with their co-release from neuropeptide Y- and somatostatin-containing striatal neurons. PMID- 2886184 TI - An aspect of the organization of the GABAergic system in the rat main olfactory bulb: laminar distribution of immunohistochemically defined subpopulations of GABAergic neurons. AB - The organization of the GABAergic system in the rat main olfactory bulb was investigated immunohistochemically using antisera against glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH), parvalbumin (PV) and methionin enkephalin-Arg6-Gly7-Leu8 (ENK). Some GABAergic neurons were shown to contain TH immunoreactivity in the glomerular layer, PV immunoreactivity in the external plexiform layer and ENK-like immunoreactivity in the granule cell layer, indicating the stratified organization of the GABAergic subsystems. PMID- 2886185 TI - Cardiovascular role of A1 catecholaminergic neurons in the rabbit. Effect of chronic lesions on responses to methyldopa, clonidine and 6-OHDA induced transmitter release. AB - We confirmed the findings of previous investigators that bilateral anodal lesions of the A1 region were associated with hypertension, bradycardia, pulmonary edema and a high mortality. All these sequelae (except the bradycardia) no longer occurred after cathodal lesions and these were therefore used to investigate the role of the catecholaminergic (CA) neurons of the A1 region in circulatory regulation. Conscious rabbits were studied 2-4 weeks after A1 lesions or sham operation, when resting mean arterial pressure (MAP) and heart rate (HR) were closely similar in both groups. We tested for differences in MAP and HR responses between lesioned and sham-operated groups: to intracisternal (i.c.) alpha methyldopa (MD) and to clonidine; and to the acute effects of i.c. 6 hydroxydopamine (6-OHDA) which elicits central CA release. Since these tests depend on the integrity of the central CA neurons, response differences between lesioned and sham-operated groups denote participation by the CA neurons of the A1 region in the central circulatory pathways. The bradycardia responses in the above tests were all smaller in lesioned than sham-operated rabbits, but there were no differences in MAP responses. Electrical stimulation of the region under alfathesin anaesthesia produced depressor responses at low frequencies and pressor responses at high frequencies. From the results in conscious rabbits CA neurons of the A1 region mainly influence the pathways regulating HR, rather than blood pressure. The changes in MAP during electrical stimulation are thus probably mediated through non-CA neurons. PMID- 2886187 TI - A small proportion of cholinergic neurones in the nucleus basalis magnocellularis of ferret appear to stain positively for tyrosine hydroxylase. AB - The immunofluorescence and peroxidase-antiperoxidase methods for immunohistochemistry were used to show that a small number of neurones in the nucleus basalis magnocellularis of ferret stain positively for what appears to be tyrosine hydroxylase, a marker for catecholaminergic neurones. With a double immunocytochemical staining method, it was confirmed that the tyrosine hydroxylase-like immunoreactivity is localized in neurones that also stain strongly for choline acetyltransferase. PMID- 2886186 TI - Somatostatin enhances neurite outgrowth and electrical coupling of regenerating neurons in Helisoma. AB - The present study tested the ability of 3 peptides (somatostatin, arginine vasopressin (AVP) and arginine-vasotocin (AVT)) to enhance neurite outgrowth from regenerating Helisoma neurons. The buccal ganglia from Helisoma were incubated either short-term in saline or longer-term (2-5 days) in medium and the extent of neurite outgrowth (induced by nerve crush) by a buccal neuron (neuron 5) was determined. Neurite outgrowth was consistently enhanced by both somatostatin and its extended analog somatostatin, but was unaffected by either AVT or AVP. The enhanced outgrowth due to somatostatin was associated with stronger electrical synapse formation between the two neurons 5, this being attributable to lower coupling resistance rather than a change in non-junctional resistance. Both the enhancement of neurite outgrowth and the increased efficacy of electrical coupling due to somatostatin were prevented by a somatostatin inhibitor. An immunohistochemical survey produced evidence for neurons containing a somatostatin-like peptide in both the cerebral ganglia and the enteric nervous system of Helisoma. It is concluded that somatostatin can act neurotrophically in the nervous system. PMID- 2886188 TI - Reinnervation of transplanted hypothalamic neurons by host aminergic fibers in rats. AB - Fetal mediobasal hypothalamic tissue which receives an extensive noradrenergic innervation in the adult brain, was implanted into the vicinity of the medial forebrain bundle of adult rats to determine whether host noradrenergic fibers would innervate the ectopically placed tissue in an organotypic manner. Tissue from the site of implantation was prepared for light and ultrastructural immunocytochemistry at 6, 12, or 20 weeks postsurgery. Putative host catecholamine fibers formed dense plexuses in localized portions of the grafts and made synaptic contacts with dendrites and somata of transplanted neurons. This suggests that a mature host central nervous system is capable of a region specific integration of transplanted neurons. PMID- 2886189 TI - Catecholamine and serotonin colocalization in projection neurons of the area postrema. AB - A large population of the rat area postrema (AP) neurons which project to the parabrachial area (PBA) are serotonergic. Many AP neurons contain tyrosine hydroxylase (TH) and are presumed to be noradrenergic. However, it was not previously known whether TH-containing AP neurons also have projections to the PBA. TH-containing and serotonin (5-HT)-containing neurons have wide and overlapping distributions within the AP, and it was therefore possible that TH and 5-HT may be contained within the same AP neurons. In the present study immunohistochemical and retrograde axonal transport techniques were combined to determine whether TH-containing AP neurons project to the PBA and whether TH and 5-HT coexist in AP neurons. Adult male rats were given bilateral injections of the retrograde transport tracer, True blue (TB), into the PBA. After a 4-day survival period, vibratome sections of the caudal brainstem were processed for both TH and 5-HT immunohistochemistry. Examination of the sections revealed that over 25% of the 5-HT and over 30% of the TH-containing AP neurons were retrogradely labelled with TB. More surprising were our findings that many AP neurons displayed both TH and 5-HT immunoreactivity and that almost 40% of these double-labelled cells project to the PBA. Our results indicate that serotonin and noradrenaline coexist in a substantial proportion of the neurons of a major ascending viscerosensory pathway from the AP to the PBA. PMID- 2886190 TI - The influence of chronic stress on multiple opioid peptide systems in the rat: pronounced effects upon dynorphin in spinal cord. AB - Recurrent exposure to intermittent electrical foot-shock (30 min, twice daily) for 7 days caused an increase in immunoreactive (ir) dynorphin and ir-alpha-neo endorphin in lumbar and cervical (but not thoracic) spinal cord as measured 16 h following the final session. At this time the level of ir-Met-enkephalin-Arg6 Gly7-Leu8 (MEAGL) was also increased at the lumbar level. An acute foot-shock depleted spinal cord dynorphin in chronically stressed but not in naive rats. No alterations in levels of ir-dynorphin or ir-MEAGL were seen in discrete brain tissues. In contrast to the brain, where no effects were seen, the levels of beta endorphin increased in both lobes of the pituitary. This change, however, was not accompanied by an alteration in levels of beta-endorphin in plasma. These data show that chronic foot-shock stress selectively influences particular pools of opioid peptides, predominantly those derived from proenkephalin B in the spinal cord and from proopiomelanocortin in the anterior pituitary. It is suggested that alterations observed in the spinal cord reflect enhanced activity of the proenkephalin B system in response to chronic nociceptive stimulation. PMID- 2886191 TI - Corticotropin-releasing factor as a transmitter in the human olivocerebellar pathway. AB - This study demonstrates that the neuropeptide, corticotropin-releasing factor (CRF), is present in neurons of the human inferior olivary complex (IOC). The medulla (including the inferior olive) and the anterior vermis of the cerebellum of 6 human controls obtained at autopsy were immunostained with an antibody directed against CRF. CRF receptors in cerebellum were localized with labeled CRF using in vitro receptor autoradiography. The great majority of neurons in all divisions of the IOC expressed CRF immunoreactivity, and CRF-immunoreactive fibers were demonstrated in the hilus of the olive and in the molecular layer of the cerebellum, where they closely resembled climbing fibers as visualized with other methods. CRF receptors were enriched in the cerebellum, with the highest density in inner portions of the molecular layer. These findings in human brain, consistent with studies in tissues from rat, cat, and monkey, demonstrate that CRF may be a peptidergic transmitter in the IOC climbing fiber system and that CRF receptors are expressed by cellular targets in the cerebellum. PMID- 2886192 TI - In vivo and in vitro expression of vasoactive intestinal polypeptide-like immunoreactivity by neural crest derivatives. AB - Qualitative and quantitative in vivo studies were performed on the development of the neuropeptide vasoactive intestinal polypeptide (VIP) in the peripheral nervous system of quail embryos. VIP-like immunoreactivity (VIPLI) was found by radioimmunoassay (RIA) from the sixth day of embryonic life onward in the sympathetic chain, the esophagus and duodenum, and from day 15 of incubation onward in the adrenal glands and the nodose ganglia. By using immunocytochemistry, we identified cells expressing VIPLI in sensory spinal ganglia of 13- to 15-day-old embryos. In neural crest cultures, cells expressing the VIP phenotype differentiated constantly under various culture conditions, in contrast to other phenotypes which had specific medium requirements, i.e. adrenergic cells or substance P-containing neurons. PMID- 2886194 TI - Quantification of synapse turnover in cell culture. AB - The on and off rates of synaptogenesis can be quantitated using a cell culture system in which embryonic retinal cells form functional synapses with striated muscle cells. Quantification showed that synapse formation and termination can occur simultaneously in culture. Quantification also revealed that some retina muscle synapses are transient, terminating within 8 h, while other synapses are much more stable. Relatively stable and transient synaptic pairs could be identified prospectively based on the strength of evoked transmission across the retina-muscle synapse. PMID- 2886193 TI - Rat brain microvessel extracellular matrix modulates the phenotype of cultured rat type 1 astroglia. AB - Astroglia from immature rat cerebral white matter which were plated on the insoluble extracellular matrix (ECM) secreted by rat cerebral microvessel endothelial cells (RCMEC) and maintained in a defined medium were induced to become stellate and to express glutamine synthetase. These effects were not elicited by RCMEC-conditioned medium. ECM secreted by rat pleural mesothelium elicited a lesser proportion of stellate astroglia and did not induce glutamine synthetase. PMID- 2886195 TI - Amphetamine- and stress-induced turning after nigral transplants in neonatally dopamine-depleted rats. AB - Neonatally dopamine-depleted rats fail to show the deficits seen in similarly lesioned adults, and no longer appear to require dopamine. Nevertheless, unilateral nigral transplants provided extensive reinnervation and were capable of modifying motor patterns. Both amphetamine and external stressors elicited contraversive turning. This raises the question of whether extrinsic dopamine innervation supplements or overrides alternative compensatory mechanisms in the neonate. PMID- 2886196 TI - Mealing and related hormone release suppress hypothalamic lesions of neonatal mice by L-glutamate. AB - Neonatal mice, under fasting conditions, are susceptible to the development of lesions in the arcuate nucleus (AN) of the hypothalamus, with high doses of monosodium L-glutamate (MSG). Feeding of nutrients (e.g., sugars and L-amino acids) has been shown to have a protective effect against the development of these lesions. The purpose of these studies was to elucidate the mechanism of this protective effect. Histopathologic examination of lesions of the AN demonstrated that feeding of weaning mice before subcutaneous administration of toxic doses of MSG suppressed the development of these lesions, as compared to fasted controls. Similarly, the number of necrotic cells in the AN of neonates administered toxic doses of MSG subcutaneously was reduced when D-glucose and L arginine were administered orally. Atropine obliterated the protective effect of D-glucose. Pretreatments consisting of gastric inhibitory polypeptide (GIP) + oral D-glucose had a protective effect of higher potency than GIP alone. Pretreatments with insulin, anorexigenic peptide (pyroGlu-His-Gly), cholecystokinin, glucagon, bombesin, and substance P (in decreasing order of effectiveness) demonstrated a protective effect against the AN lesion in neonates, whereas somatostatin and beta-endorphin had no effect. Results suggest that the protective effect of nutrients may in part be due to the stimulation of peptide hormone release during the postabsorptive phase. It is postulated that the effect of entero-pancreatic hormone, especially insulin, is to enhance the tolerance of AN neurons of neonatal mice to the toxic dose of L-glutamate. PMID- 2886197 TI - Light and electron microscopic study of somatostatin-like immunoreactive neurons in rat hippocampus. AB - The distribution and fine structure of somatostatin-like immunoreactive neurons in rat hippocampus and gyrus dentatus were investigated by light and electron microscopic immunocytochemistry. Somatostatin-like immunoreactive neuronal perikarya and fibers could be visualized by using modified PAP immunocytochemistry. Immunoreactive neurons were selectively localized in the stratum orience of the hippocampus and hilar region of the gyrus dentatus, however, immunoreactive neurons were also sparsely observed throughout hippocampal formation. Somatostatin-like immunoreactive varicosities were abundantly distributed in the stratum pyramidale and some of them were considered to terminate on the pyramidal cells. Somatostatin-like immunoreactive neurons in the hippocampal formation generally contained many mitochondria, well-developed rough surfaced endoplasmic reticulum (rER), polysomes and some dense granules. Immunoreactivity was observed especially in the dense granules and membrane of rER. Pre- and post-synaptic elements of somatostatin-like immunoreactive neurons were detected throughout the hippocampal formation. PMID- 2886199 TI - [Absence of linkage between Alzheimer's disease and a polymorphic probe of the long arm of chromosome 21]. AB - The hypothesis of an eventual linkage between Alzheimer's disease (AD), a presenile dementia, and the genomic probe GMG 21 S3, located on the long arm of chromosome 21, has been investigated in a large family originating from Calabria, in which AD is transmitted as an autosomal dominant mendelian trait. Analysis of the Bgl II restriction polymorphism, after molecular hybridization with the probe, of DNAs coming from 28 subjects of a pedigree, from which 10 individuals are affected, allowed to demonstrate that there wasn't any linkage between AD and the marker studied. PMID- 2886200 TI - Treatment of elevated intraocular pressure with concurrent levobunolol and pilocarpine. AB - Between July 1983 and January 1986, 54 patients with open-angle glaucoma or ocular hypertension were treated for 3 months with 2% pilocarpine hydrochloride (given four times daily) and one of two beta-adrenoceptor blocking drugs, levobunolol hydrochloride (0.5% [17 patients] or 1% [19 patients]) or 0.5% timolol maleate (18 patients), given twice daily. Before entry into the study all patients had had stable intraocular pressure (IOP) with treatment with 0.5% timolol and 2% pilocarpine. Stable IOP was successfully maintained in up to 88% of the patients in the two levobunolol-pilocarpine groups and in 83% of those in the timolol-pilocarpine group. Two patients experienced adverse reactions: one, who received timolol and pilocarpine, suffered blepharoconjunctivitis, and the other, who received 1% levobunolol and pilocarpine, experienced bradycardia. The results indicate that the levobunolol-pilocarpine regimens were as safe and effective as the timolol-pilocarpine regimen in stabilizing IOP. PMID- 2886201 TI - Diabetes alters the reactivity of myocardium to a thromboxane analogue. AB - Atrial contractile response to U-46619 was studied in auricles from normal and acutely diabetic rats. U-46619 induced an increment of dF/dt in diabetic atria, whereas nondiabetic auricles elicited a negative contractile effect. Blockers of arachidonic acid metabolism via cyclooxygenase inhibited the stimulatory action of U-46619. The stimulant action of the thromboxane A2 mimetic was attenuated when diabetic auricles were incubated with lipoxygenase(s) blocking agents. Results suggest that in diabetic atria, the abnormal inotropic effect induced by U-46619 may be associated with thromboxane formation and with lipoxygenase(s) metabolites. PMID- 2886198 TI - Respiratory and vasomotor effects of excitatory amino acid on ventral medullary surface. AB - Three glutamic acid analogues, N-methyl-D-aspartic (NMDA), quisqualic (QQ), and kainic (KAI) acids were applied topically to the ventral surface of the medulla (VMS) in paralyzed, vagotomized and carotid sinus denervated cats hyperventilated to apnea. Respiratory and vasomotor effects were assessed by changes in phrenic nerve activity and systemic arterial blood pressure. All three agents to varying degrees raised systemic blood pressure, but only NMDA consistently initiated phrenic nerve activity at pCO2 levels below that observed in control trials. KAI and QQ raised blood pressure even in those animals in which they had little effect on initiating phrenic nerve activity. Furthermore, respiratory responses were obtained from localized areas on VMS, namely the intermedio-caudal zone (I-C areas); whereas blood pressure elevations could be obtained from wider VMS areas including the rostral zone (R areas). In addition, the effects of the three amino acids on blood pressure were quantitatively different with KAI causing much greater increases in blood pressure than QQ or NMDA. The respiratory and vasomotor effects of NMDA and QQ were blocked by the use of 2-amino-5 phosphonovaleric acid and L-glutamic acid diethylester, their respective antagonists. The results suggest that neurons in the VMS which cause respiratory and vasomotor responses are not identical. Cells containing receptors stimulated by NMDA predominantly increase respiration, whereas cells containing receptors excited by KAI are more effective in eliciting vasomotor responses. PMID- 2886202 TI - Cycloheximide blocks insulin-like growth factor I but not somatostatin inhibition of growth hormone secretion. AB - Growth hormone secretion is controlled by the two hypothalamic hormones, growth hormone releasing factor (GRF) and somatostatin. In addition, the insulin-like growth factors (IGF or somatomedins) which are themselves growth hormone dependent, inhibit growth hormone release in vitro, therefore acting to close the negative feedback loop. The studies reported here examine some of the differences between inhibition of growth hormone secretion by somatostatin and IGF-I in vitro. The major finding is that cycloheximide, a protein synthesis inhibitor, blocks inhibition of GRF-stimulated growth hormone release caused by IGF-I, without changing the inhibition caused by somatostatin. The experiments were done by exposing mixed rat adenohypophysial cells to secretagogues with or without cycloheximide for 24 h in a short term culture. Somatostatin (0.6 nM) totally blocked rat GRF (1 nM) stimulated growth hormone release to values 48% of control (nonstimulated values), while IGF-I (27 nM) only reduced the GRF-stimulated growth hormone release by 27 +/- 3% (N = 5). Cycloheximide (15 micrograms/mL) totally blocked the effect of IGF-I but not somatostatin. A low concentration (0.12 nM) of somatostatin, which only partly inhibited growth hormone release, was also unaffected by cycloheximide. In purified rat somatotrophs, somatostatin (0.1 nM) inhibited GRF-stimulated cAMP levels slightly and reduced growth hormone release while IGF-I (40 nM) had no effect. We suggest that IGF-I inhibits only the secretion of newly synthesized growth hormone, while somatostatin inhibits both stored and newly synthesized growth hormone pools. PMID- 2886203 TI - Central and peripheral actions of salicylate in altering nonpyrogenic thermoregulation of rats. AB - The effects on body temperature of intracerebroventricular and intraperitoneal sodium salicylate were evaluated in anesthetized and nonanesthetized, nonrestrained rats. Also, the effects of various neurotransmitter receptor blocking drugs were evaluated on salicylate-induced hypothermia of nonanesthetized animals. Sodium salicylate, 150-350 mg/kg induced a dose-related hypothermia of unanesthetized animals. However, in anesthetized animals, marked hyperthermia was observed. In unanesthetized, unrestrained rats, intracerebroventricular administration of 1.0 mg/h salicylate caused greater hypothermia than peripheral administration of salicylate, 350 mg/kg. Salicylate hypothermia was unaffected by para-chlorophenylalanine, cyproheptadine, or naloxone, and was only partially inhibited by pimozide. These results strongly suggest a potent direct action of salicylate within the central nervous system to induce hypothermia, and suggest possible involvement of dopaminergic neurons in this process. PMID- 2886204 TI - Prevention of hypertension and maintenance of normotension in spontaneously hypertensive rats is dependent on continuous severe dietary sodium restriction. AB - Spontaneously hypertensive rats were placed on a very low (9 mumol/g) or control (101 mumol/g) sodium diet at birth or 4 weeks of age. These diets were continued to 16 weeks of age, or at 10 weeks were increased from 9 to 26 or 101 mumol/g. Sodium restriction initiated up to 4 weeks of age and continued to 16 weeks of age severely retarded growth, prevented the development of hypertension, and reduced effective sympathetic activity as assessed by the response of blood pressure to ganglionic blockade. Only a small increase in sodium intake at 10 weeks of age (to 26 mumol/g or more) resulted in a marked increase in growth rate, an elevation of blood pressure, and a return of the response to ganglionic blockade towards normal. These data indicate that very severe sodium restriction must be continuous to maintain decreased sympathetic activity and normal blood pressure in spontaneously hypertensive rats. It appears that severe dietary sodium restriction suppresses one or more of the mechanisms involved in normal growth and development of hypertension in spontaneously hypertensive rats, but these mechanisms may still proceed once the sodium intake is increased. PMID- 2886205 TI - Evaluation of feet and skeletons of limbs from pigs treated with a repartitioning agent, cimaterol. AB - Recently, beta-adrenergic agents, which repartition muscle and fat, have been used to develop more muscular carcasses in broilers, steers, lambs, and pigs. Cimaterol, one such repartitioning agent, effectively improves carcass quality in pigs. Since the mode of action of repartitioning agents is uncertain, and because they may indirectly affect skeletal development or the integrity of feet, the purpose of this study was to assess the effect of cimaterol on selected growth cartilages and feet. Pigs were randomly placed in four groups and fed a ration that included Cimaterol at 0.00, 0.25, 0.50, or 1.00 mg/kg. At 100 kg live weight, pigs were slaughtered and selected growth cartilages, bones, and feet were examined macroscopically, radiologically, and microscopically. Although the majority of pigs had lesions in feet, or had dyschondroplastic changes typical of osteochondrosis in many growth cartilages, particularly physes, there were no significant differences in frequency of pigs with lesions between groups. Cimaterol enhanced carcass quality with no detrimental effect on bones or feet. PMID- 2886206 TI - Toxigenic characteristics of Clostridium perfringens type C in enterotoxemia of domestic animals. AB - Eleven Clostridium perfringens type C strains isolated from fatal cases of hemorrhagic enterotoxemia of Canadian calves, a piglet, and a foal were studied for the production of soluble antigens. All the isolates from calves and a foal failed to produce delta toxin, but were capable of producing large amounts of lethal beta toxin. A strain isolated from a piglet produced delta, but very little beta toxin. Other differences were relatively minor. The results indicated that young domestic animals may be susceptible to all subtypes of C. perfringens type C. A simple method of using blood agar plates coated with type A antiserum for demonstration of hemolytic patterns was found advantageous in differentiation of C. perfringens strains. PMID- 2886207 TI - Antagonism of xylazine induced sedation by idazoxan in calves. AB - Idazoxan was studied at three dose rates to assess its potential as an antagonist to xylazine. Calves in the study group were initially given xylazine at a dose rate of 0.2 mg/kg intravenously followed 12 minutes later by idazoxan at a dose rate of either 0.05, 0.075 or 0.10 mg/kg intravenously. A control group received a saline injection instead of idazoxan. All three dose levels of idazoxan successfully reversed the xylazine induced central nervous depression and all animals stood within two minutes of injection. No residual signs of sedation were noticed and relapse did not occur. In addition idazoxan was successful in reversing respiratory and cardiovascular depression produced by xylazine. The results indicated that idazoxan may be used for rapid reversal of xylazine induced sedation in calves. PMID- 2886208 TI - The static biomechanical examination and its importance in occupational medicine. AB - This article presents a review of the biomechanical examination of the lower extremities. Various techniques for taking measurements are presented in an orderly fashion; a format is given to decrease the total time spent performing examinations. The author proposes that, because lower extremity injury and disease account for a significant portion of compensation cases, this examination be used as a screening device for employment. This preventive measure may decrease health care costs to employers and needless injuries to their employees. PMID- 2886209 TI - Occupational biomechanics of athletes and dancers: a comparative approach. AB - Muscle strains represent more than a third of all injuries in both dancers and athletes. Although often overlooked, anatomic variations play an important role in the etiology of these injuries, as does strength imbalance between agonists and antagonists. The incidence of spondylolysis is unusually high in ballet dancers and certain athletic groups, such as gymnasts, javelin throwers, and weight-lifters. Mechanical factors play a major role and can be exacerbated by congenital abnormalities. Various permanent adaptive musculoskeletal changes have been described both in dancers and athletes, especially those that start at a very young age. Task-related adaptive changes can also be seen in isokinetic strength measurements of various muscle groups, such as the spine muscles of Flamenco dancers. Shoes and floor surfaces can be directly responsible in part or in whole for many sports and dance injuries. "Vibration-pressure" diagrams are suggested as an objective way to document their effect on biomechanical behavior. PMID- 2886210 TI - Do Oriental psychiatric patients receive different dosages of psychotropic medication when compared with occidentals. AB - The literature suggests the possibility of different drug dosage requirements between patients of different ethnic origins. This study thereby attempted to investigate the average dosages of psychotropic medications being prescribed for Orientals versus Occidentals using a retrospective drug history review and an international opinion survey. The retrospective drug history review compared drug dosages for four commonly used psychotropic medications in well matched Oriental and Occidental populations. Data from this review showed that final/maintenance dosages of amitriptyline were significantly lower for Orientals than Occidentals. The opinion survey assessed the responses of psychiatrists in the Orient, as well as in North America, with respect to average dosages prescribed for the two populations; their beliefs in possible variability and causes underlying the variability. Data indicated that significantly lower dosages of chlorpromazine, phenelzine, diazepam, and chlordiazepoxide are being prescribed for Orientals as compared with Occidentals. Beliefs in differences were dependent upon the degree of exposure to Orientals. Suggested etiological factors underlying the variability were usually related to drug metabolism, side effects, and body weight. In both types of studies, Orientals appeared to have lower prescribed dosages than Occidentals. The lower dosages, however, appeared to be a function of the physician's experience in treating the Oriental population. PMID- 2886211 TI - Poorly controlled EPS: risk factors for NMS. PMID- 2886212 TI - Frequent alterations of specific reiterated DNA sequence abundances in human cancer. AB - An in-gel renaturation method allows the visualization, quantitation, and initial characterization of reiterated DNA restriction fragments (RRFs) without prior possession of their probes. Using this method we analyzed EcoRI restricted DNAs from ten human tumors, paired normal tissues from these patients, ten unpaired tumors, and 26 noncancer patients. Frequent qualitative and quantitative differences in the relative radioactive intensities of all or specific RRFs in the DNA from different individuals have been observed. However, we also report frequent two- to ten-fold alterations in the relative radioactive intensities of several specific RRFs in tumor-control analyses of DNA from the same individual. A 0.65-kb alphoid-like DNA RRF was decreased in six tumors and increased in none. Moreover, a new 1.55-kb RRF was observed in two colon cancer DNAs. Several new RRFs, suggestive of gene amplification, were detected in a neuroblastoma, two of which were also seen in a glioma. These data support frequent qualitative and quantitative alterations of specific reiterated DNA sequences in human cancer when compared with paired controls. This approach will allow the future characterization of specific DNA sequences whose patterns of altered reiteration suggest a role in the emergence of specific malignancies. PMID- 2886213 TI - Loss of heterozygosity at autosomal and X-linked loci during tumor progression in a patient with melanoma. AB - Restriction fragment length polymorphisms at 61 autosomal and 7 X-linked loci were screened for heterozygosity in cell lines derived from 6 independent metastases and autologous B-cells from a patient with melanoma. Segregations resulting in the loss of heterozygosity were detected in the tumor cells at 8 of 16 autosomes with at least 1 informative locus and at the 3 informative X-linked loci. With a single exception, karyotypic abnormalities were not detected in the region of loci where loss of heterozygosity had been detected. Three patterns of loss were identified: unique segregations in cells from a single metastasis; segregation of the same alleles in different subsets of metastases; and identical segregations in all 6 metastases. The monoclonal derivation of the 6 metastases is supported by the inactivation of the same X-chromosome and the presence of identical segregation at loci on chromosomes 9 and X. Analysis of the patterns of segregation in the metastatic tumor cells permitted the development of a genealogy of tumor progression in this patient and the development of a model of tumor progression which describes the accumulation of selectively neutral and advantageous segregations in metastatic tumor cells. PMID- 2886214 TI - Histamine and growth: interaction of antiestrogen binding site ligands with a novel histamine site that may be associated with calcium channels. AB - N,N-Diethyl-2-[(4-phenylmethyl)-phenoxy]ethanamine hydrochloride (DPPE) is a novel paradiphenylmethane derivative with antiproliferative and antiestrogenic properties. Like tamoxifen (TAM), DPPE binds to the microsomal antiestrogen binding site with high affinity (Kd approximately 50 nM), but, conversely, not to estrogen receptor or calmodulin. We now demonstrate that DPPE competes for [3H]histamine binding in rat cerebral cortex with an affinity (Ki = 4.5 +/- 2.6 X 10(-6) M) significantly greater than that of the H1 antagonist pyrilamine (Ki = 7.2 +/- 2.2 X 10(-5) M), despite the previous demonstration that pyrilamine is up to 1000 times more potent than DPPE in antagonizing histamine-induced contraction in canine tracheal smooth muscle. DPPE demonstrates antiproliferative activity against MCF-7 cells at concentrations between 1 X 10(-7) and 1 X 10(-5) M; the IC50 value of DPPE for growth inhibition at 7 days in this assay is 5 X 10(-6) M, a value equivalent to its Ki value for histamine binding. DPPE also competes for [3H]verapamil binding in membranes from whole rat brain with an affinity equal to that for verapamil (Kd = 4.0 +/- 1.8 X 10(-7) M); however, verapamil competes for [3H]DPPE binding in brain membranes and rat liver microsomes with an affinity markedly lower (Ki approximately 1 X 10(-4) M) than that of DPPE, suggesting allosteric interactions between the verapamil and DPPE sites. Unlike DPPE, verapamil is not antiproliferative in vitro against MCF-7 cells at concentrations up 1 X 10(-5) M, but, like DPPE, is cytotoxic at concentrations of 1 X 10(-4) M. In immature oophorectomized rats, verapamil or DPPE alone is antiuterotropic; however, verapamil shows no antagonism of exogenous estradiol on uterine growth, as opposed to DPPE which is a partial antagonist. Thus, the antiproliferative and antiestrogenic properties of DPPE either are not associated with calcium channel antagonism, or result from a qualitatively different effect on channels than verapamil. The in vitro antiproliferative effect of DPPE (7.5 X 10(-6) M) on MCF 7 cells at 72 h is significantly reversed by 10 mM L-histidine (70.2 +/- 12.6% reversal) and L-methionine (92.4 +/- 11.1% reversal), but not by L-ornithine, L arginine, L-phenylalanine, or exogenous histamine. At lower concentrations of TAM (0.75 X 10(-6) M), where growth inhibition is estrogen-reversible, L-ornithine, but not L-histidine or L-methionine, causes significant reversal of growth inhibition (66.8 +/- 13.3%; p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2886215 TI - Complete or partial homozygosity of chromosome 13 in primary retinoblastoma. AB - Sixteen retinoblastomas were examined with chromosome 13 polymorphic probes to determine the frequency of homozygosity for the chromosome in the tumors. Each of the tumors had two cytogenetically normal appearing No. 13 chromosomes. Nontumorous cells from the same patients were heterozygous for the various polymorphic chromosome 13 probes used. At least partial homozygosity for a single chromosome 13 was observed in 75% of the tumors. These studies confirm and extend previous studies which suggest that homozygosity or hemizygosity at RBI occurs in the majority of retinoblastomas. We also demonstrate in an additional tumor that rapid clonal evolution from hemizygosity to homozygosity can occur in the tumor. PMID- 2886216 TI - Amplification and enhanced expression of the c-Ki-ras2 protooncogene in human embryonal carcinomas. AB - Two cell lines of human embryonal carcinoma, Tera-1 and Tera-2, have been found to exhibit a 4- to 6-fold amplification of protooncogene c-Ki-ras2. The polyadenylic acid selected RNA also showed 8-fold or greater enhancement, showing marked elevation in the level of two major mRNAs, 5.7 and 4.0 kilobases, and two additional minor mRNAs, 2.3 and 1.2 kilobases, as compared with those of a normal human embryonic fibroblast cell line, MRC-5. More than one-half of the number of tumor samples obtained from metastatic human embryonal carcinomas also showed c Ki-ras2 gene amplification and enhanced mRNA expression. However, the c-Ki-ras2 gene amplification did not always lead to enhanced mRNA expression, and some embryonal carcinomas showed mRNA overexpression without apparent c-Ki-ras2 gene amplification. These results suggest that human embryonal carcinomas may have c Ki-ras2 amplification and/or overexpression before in vitro culture. Among various chromosomal changes observed in Tera-1 and Tera-2 cells, there were anomalies in chromosome 12 in which c-Ki-ras2 is located although these karyological changes alone could not account for the amplification observed. It is suggested that the genomic instability and active DNA replication during the early developmental period may give rise to changes involving c-Ki-ras2 which may contribute to oncogenic processes. PMID- 2886218 TI - Basis for the selective cytotoxicity of rhodamine 123. AB - Using rat liver mitochondria we determined that the primary biochemical target for inhibition of mitochondrial bioenergetic function by rhodamine 123 (Rh123) was FoF1-ATPase and that the amount of Rh123 associated with mitochondria is proportional to the mitochondrial membrane potential. Inhibition of coupled respiration by Rh123 in mitochondria isolated from CX-1, a Rh123-sensitive carcinoma cell type, and CV-1, a Rh123-insensitive normal epithelial cell type, was linearly related to the amount of Rh123 added (micrograms/mg protein) with CX 1 mitochondria exhibiting 2-fold greater inhibition compared to CV-1 mitochondria at any given amount of dye. The inhibition pattern for mitochondria isolated from MIP101, a Rh123-insensitive carcinoma cell type, was nonlinear, exhibiting greater sensitivity than CV-1 mitochondria at very low amounts of Rh123 but becoming less sensitive than either CV-1 or CX-1 at higher amounts. Rh123 inhibited FoF1-ATPase activity to a similar extent and in a concentration dependent manner in both CV-1 and CX-1 mitochondria, but a different and complex pattern of inhibition was apparent for MIP101 mitochondria. Moreover, mitochondria from the 2 carcinoma cell types, CX-1 and MIP101, had higher membrane potentials (163 +/- 7 and 158 +/- 8 mV, respectively) than did mitochondria from the normal epithelial cell type, CV-1 (104 +/- 9 mV). It was concluded that differences in both mitochondrial membrane potential and sensitivity of FoF1-ATPase contribute to the selective cytotoxicity exhibited by Rh123 for certain cell types in vitro. PMID- 2886217 TI - Mechanism of protection against aflatoxin tumorigenicity in rats fed 5-(2 pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz) and related 1,2-dithiol-3 thiones and 1,2-dithiol-3-ones. AB - 1,2-Dithiol-3-thiones, reported constituents of cruciferous vegetables, are five membered cyclic sulfur-containing compounds with antioxidant, chemotherapeutic, and chemoprotective activities. The effects of dietary administration of a substituted 1,2-dithiol-3-thione, oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiol 3-thione], a potent antischistosomal agent, on aflatoxin B1 (AFB1) metabolism, DNA adduct formation, and hepatic tumorigenesis were examined in male F344 rats. Rats were fed graded doses of oltipraz (0.01-0.1%) for 4 wk. During the second and third wk of oltipraz feeding rats were gavaged with 250 micrograms of AFB1/kg five times a wk. Rats were finally restored to control diet 1 wk after cessation of AFB1 dosing. At 4 months focal areas of hepatocellular alteration were identified and quantitated by staining sections of liver for gamma-glutamyl transpeptidase activity. Treatment with oltipraz at all doses reduced by greater than 90% the volume of liver occupied by gamma-glutamyl transpeptidase-positive foci. Levels of AFB1 bound to hepatic DNA were reduced between 40 and 80% in animals fed increasing doses of dietary oltipraz (0.01-0.1%) for 1 wk prior to a single exposure to AFB1. Feeding of the higher levels of oltipraz led to marked increases in the specific activity of glutathione S-transferases, presumably serving to facilitate the detoxication of the ultimate electrophilic form of AFB1, the 8,9-oxide. At low dietary concentrations of oltipraz (0.01%), the only inductive effects seen were on the activities of selected cytochrome P-450 monooxygenases. Therefore, the protection afforded by oltipraz may be due to both the enhancement of electrophile detoxication pathways as well as modified oxidative metabolism of AFB1. In in vitro metabolism studies with hepatic post mitochondrial supernatant, low-dose oltipraz pretreatment facilitated the oxidative production of aflatoxins P1 and Q1, but not M1, from AFB1. High-dose (0.1%) oltipraz pretreatment enhanced the primary metabolism of AFB1 to aflatoxins P1, M1, and Q1 as well as the formation of chloroform-insoluble metabolites. Feeding studies with a series of 1,2-dithiol-3-thione and 1,2 dithiol-3-one derivatives of oltipraz demonstrated that the inductive activity for cytochrome P-450-dependent monooxygenases and electrophile detoxication enzymes, such as glutathione S-transferases, could be readily separated by minor modifications of the 1,2-dithiol-3-thione structure. The unsubstituted 1,2 dithiol-3-thione nucleus strongly induced electrophile detoxication enzymes, but not the monooxygenases, and was the most effective inhibitor of the binding of AFB1 to hepatic DNA in vivo.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2886219 TI - Appearance of high affinity receptors for type beta transforming growth factor during differentiation of murine embryonal carcinoma cells. AB - Recent studies have demonstrated that type beta transforming growth factor (TGF beta) not only influences cell growth but also affects cell differentiation. In the present study, two different embryonal carcinoma (EC) cell lines and their differentiated cells were examined for the presence of TGF-beta receptors and for their responses to this factor. F9 and PC-13 EC cells bind little, if any, TGF beta and do not appear to respond to TGF-beta in monolayer or soft agar cultures. Treatment of both EC cell lines with retinoic acid leads to the appearance of irreversibly differentiated cells that begin to exhibit receptors for TGF-beta by 48 h. After an additional 3-5 days, the differentiated cells express approximately 6000 high affinity receptors for TGF-beta, with an apparent dissociation constant of 45 PM. In contrast to the results observed with the parental EC cells, TGF-beta influences the growth of the differentiated cells cultured in both serum-free and serum-containing media. However, TGF-beta, alone or in combination with other growth factors, does not induce the differentiated cells to form colonies in soft agar. The possible relationship of these results to the roles of growth factors during early mammalian development is discussed. PMID- 2886220 TI - Mechanism of vasodilation by nitrates: role of cyclic GMP. AB - Nitrovasodilators relax vascular smooth muscle by stimulating soluble guanylate cyclase (GC). The resulting rise in cGMP probably initiates Ca extrusion from the smooth muscle cell which causes relaxation. Since repeated administration of organic nitrates, particularly nitroglycerin, leads to tolerance, i.e. a decrease in the vasodilator effect, it was studied whether (a) tolerance was a peripheral phenomenon occurring in the vascular smooth muscle, and (b) was due to an impairment of GC activation. In isolated circular strips of bovine coronary arteries, 90 min pretreatment with nitroglycerin greatly lowered the relaxing as well as the cGMP increasing response to nitroglycerin, indicating tolerance induction. Tolerance, although to a lesser extent, was also obtained with other organic nitrates under similar conditions, including IS 5-MN. Little (nitroprusside Na) to negligible tolerance was obtained with sodium nitrate and SIN-1, the active metabolite of molsidomine. The latter group of drugs stimulated soluble GC in vitro in the absence of cysteine whereas organic nitrates required the presence of this thiol. Preincubation with nitroglycerin almost completely inactivated GC whereas other organic nitrates had little effect. The results indicate that tolerance is caused by an impairment of GC function in the smooth muscle cell, particularly when elicited by nitroglycerin, and that differences in the degree of tolerance development by various nitrovasodilators are possibly due to different mechanisms of activation and inactivation of GC as well as differences in cysteine requirement. PMID- 2886222 TI - Drug interaction and anesthesia. PMID- 2886221 TI - Effects of antihypertensive drugs on lipid metabolism. AB - Despite the well-established correlation between coronary heart disease (CHD) and hypertension, conventional antihypertensive therapy with diuretics and beta adrenergic blockers has failed to provide protection against CHD. A possible explanation for this failure is the unfavorable effect such drugs have on lipid metabolism. To compare the lipid profiles of commonly used antihypertensive drugs, a survey was made of selected studies from the literature. Diuretics and selective and nonselective beta-blockers were found to have adverse effects on blood lipids. Beta-blockers with intrinsic sympathomimetic activity, labetalol, methyldopa, and calcium channel blockers are lipid neutral, whereas alpha adrenergic blockers seemed to have a favorable effect on lipid metabolism. Controlled clinical trials with drugs that have no adverse effects on lipid metabolism are needed to establish the long-term clinical importance of such agents. PMID- 2886223 TI - Replacement of chronically administered anticholinergic drugs by amantadine in outpatient management of chronic schizophrenia. AB - Anticholinergic drugs have been shown to impair new memory acquisition. In a double-blind study, 22 chronically schizophrenic patients had the anticholinergic drugs that they had been taking to control the extrapyramidal side effects (EPSE) of neuroleptic drugs discontinued and were randomly assigned to treatment either with benztropine (an anticholinergic) or with amantadine (which has little or no anticholinergic effect). The EPSE of five of the ten patients assigned to amantadine could not be adequately controlled with that drug alone, and these patients were withdrawn from the study prematurely. The five patients who completed the six-week trial on amantadine showed improved performance on tests of memory acquisition in comparison with patients treated with benztropine. Global inspection of the results showed that only 36% of the patients taking benztropine showed improvement in memory acquisition at the four- and six-week assessments, whereas 80% of the amantadine users showed improvement at the four week assessment. Analysis of covariance, however, revealed that the performance of the latter group decreased almost to baseline at six weeks, as an additional two of the remaining patients developed distressing EPSE. PMID- 2886224 TI - Coated and smooth vesicles participate in acetylcholine receptor transport. AB - The removal of the acetylcholine receptors (AChRs) from the surface of muscle cells serves as an important mechanism in the regulation of the AChR turnover rate. Our previous studies have shown that cultured myotubes contain coated pits and vesicles bearing alpha-bungarotoxin (alpha BTX)-binding sites (Bursztajn 1984; Bursztajn and Fischbach 1984). In this study we have used alpha BTX conjugated to horseradish peroxidase (HRP) and quantitative electron microscopy to determine the intracellular pathway(s) of acetylcholine receptors during the internalization process. To accomplish this, cultured rat myotubes were incubated with alpha BTX-HRP at 4 degrees C after which cells were washed and incubated at 37 degrees C for 0 min to 2 h. After warming the cells, coated pits, coated vesicles and smooth membraned vesicles containing the peroxidase reaction product were present. A threefold increase in coated vesicles containing the reaction product was observed 1 min after warming the cells. The number of smooth membraned vesicles remained constant at this time point. However, 5 to 15 min after warming the cells, a fivefold increase in the number of smooth membraned vesicles was observed. After 1 h at 37 degrees C the reaction product was present in the lysosomal like bodies, but was not observed in the Golgi complex or the small coated vesicles associated with the Golgi complex. Our observations indicate that there is a size segregation between those coated vesicles containing alpha BTX-HRP reaction product and those in which reaction product is absent. Our studies also suggest that within minutes of AChR internalization coated vesicles lose their coat and become smooth-membraned vesicles. PMID- 2886225 TI - Amacrine cells with neurotensin- and somatostatin-like immunoreactivities in three species of teleosts with different color vision. AB - Neurotensin- and somatostatin-like immunoreactivities were localized by pre embedding techniques in retinal whole-mounts and radial sections of a monochromatic glass catfish (Kryptopterus bicirrhis), a dichromatic cichlid species (Aequidens pulcher), and the tetrachromatic roach (Rutilus rutilus). Both neuropeptides were observed in perikarya and processes of amacrine cells. For a precise identification of cell types, tangential and radial views were correlated with Golgi-impregnated material. The dendritic pattern defining the morphological subtype of amacrine cells was determined by the given neuropeptide or by the species-specific degrees of complexity of retinal structure and function. Neurotensin-like immunoreactivity was localized in amacrine cells of intermediate size, radial symmetry and dendrites with numerous varicosities; they were monostratified in sublayer 3 of the inner plexiform layer. This cell type was common to all three species. In the mono- and dichromatic retinas, a single type of amacrine cell with somatostatin-like immunoreactivity was found with radially oriented, varicose dendrites in sublayer 5. In the tetrachromatic roach retina, two somatostatin-positive amacrine cell types were found with very different patterns of ramification; furthermore, both of these types occurred in more than one sublayer. Possible functional implications for color vision of neuropeptide specific amacrine cells with uniform morphology in all three species and those with a more varied morphology in the tetrachromatic roach are discussed. PMID- 2886227 TI - Localization of the Huntington's disease gene to a small segment of chromosome 4 flanked by D4S10 and the telomere. AB - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder of late onset, characterized by progressive motor disturbance, psychological manifestations, and intellectual deterioration. The HD gene has been genetically mapped by linkage to the DNA marker D4S10, but the exact physical location of the HD defect has remained uncertain. To delineate critical recombination events revealing the physical position of the HD gene, we have identified restriction fragment length polymorphisms for two recently mapped chromosome 4 loci, RAF2 and D4S62, and determined the pattern of segregation of these markers in both reference and HD pedigrees. Multipoint linkage analysis of the new markers with D4S10 and HD establishes that the HD gene is located in a very small physical region at the tip of the chromosome, bordered by D4S10 and the telomere. A crossover within the D4S10 locus orients this segment on the chromosome, providing the necessary information for efficient application of directional cloning strategies for progressing toward, and eventually isolating, the HD gene. PMID- 2886226 TI - Regulation of Thy-1 gene expression in transgenic mice. AB - Genomic DNA fragments encompassing the human Thy-1 or mouse Thy-1.1 gene have been microinjected into pronuclei of mouse embryos homozygous for the Thy-1.2 allele. In the resulting transgenic mice, the human gene is expressed in a pattern characteristic of normal human tissues, and is not influenced by the pattern of endogenous mouse Thy-1 expression. The mouse Thy-1.1 gene fragment is expressed in a pattern typical of mouse Thy-1, although it is more limited in its distribution. The results indicate the presence of multiple cis-acting regulators of Thy-1 gene expression that have changed in both their character and arrangement over the course of Thy-1 gene evolution. PMID- 2886229 TI - [Immuno-histochemical study of experimental epidemic hemorrhagic fever]. PMID- 2886228 TI - Neonatal tolerance induction in the thymus to MHC-class II-associated antigens. III. Significance of hemopoietic stem cells for induction and maintenance of Mls tolerance by continuous supply of tolerance-inducing nonlymphocytes. AB - The role of hemopoietic stem cells and other cell types in the induction and maintenance of immunologic tolerance in the thymus was investigated by intravenous injection of Mls-semi-allogeneic cells into newborn mice less than 24 hr after birth. Mls-specific tolerance was induced by inoculation of peritoneal cells and thymus cells, and the tolerant state was compared with that induced by bone marrow cells which had hemopoietic stem cell activity and were able to create a stable chimera in both central and peripheral lymphoid organs. When peritoneal or thymus cells were injected, the level of tolerance attained was proportional to the number of cells injected, though peritoneal cells were 20 times as effective as thymus cells. In vivo functions of tolerance-inducing cells and their immediate precursors were radiosensitive and belonged to a Thy-1-, nylon-wool-nonadherent (probably non-B), weakly Sephadex G-10-adherent cell population. Tolerance induced by peritoneal cell injections was transient, starting to terminate within the first 2 weeks of life, while tolerance caused by bone marrow cell injections persisted through more than 6 weeks. Such transient tolerance induced by the former became long-lasting when followed by an additional injection of bone marrow cells, which did not cause thymic lymphocyte chimerism. All data indicated that bone marrow stem cells were engaged in tolerance induction and maintenance by continuously supplying tolerance-inducing nonlymphocytes. PMID- 2886230 TI - [Pharmacological study on an irreversible ligand of opioid receptors- 7 alpha-bis (beta-chloroethyl) amino-6, 14-endoetheno-tetrahydrooripavine (alpha-CAO)]. PMID- 2886231 TI - [Isolated choroidoretinal vasculitis and autoimmunity. Discussion of a case]. PMID- 2886232 TI - Altered drug metabolizing potential of acinar cell lesions induced in rat pancreas by hydroxyaminoquinoline 1-oxide. AB - Foci of atypical acinar cells observed in male rats 1 year after a single injection of hydroxyaminoquinoline 1-oxide (HAQO) were assessed immunohistochemically for altered expression of a number of enzyme forms considered to play important roles in drug metabolism. The pancreatic lesions, classified as of either basophilic or eosinophilic type on histological appearance, demonstrated distinctive patterns of altered enzyme phenotype. On the one hand, the basophilic foci composed of enlarged cells/nuclei with very prominent nucleoli were characterized by increase in GST-P, G6PD and P450 PB1 and MC2 forms. The eosinophilic type, in contrast, comprised smaller cells demonstrating elevated P450 MC1 and PB1 but not MC2, normal G6PD and strong GST-P binding limited only to a proportion of the nuclei. Both shared decreased GGT and almost total lack of GST-B positive connective tissue and ductular elements. Apparent islet cell lesions and normal islet tissue were characterized by a distinct enzyme phenotype strongly positive for all P450 species investigated. The results indicate that HAQO-induced putative preneoplastic pancreatic lesions, like equivalent carcinogen associated with focal populations in liver, kidney and ductular pancreas, demonstrate a non-random altered expression of specific drug metabolizing enzyme species. PMID- 2886234 TI - Effects of chronic progressive myocardial hypertrophy on indexes of cardiac autonomic innervation. AB - The development of cardiac hypertrophy is associated with marked changes in cardiac autonomic innervation. Significant and sustained reductions of myocardial catecholamine stores and activities of tyrosine hydroxylase and dopamine beta hydroxylase have been reported in models of acutely induced ventricular hypertrophy. Conversely, activity of choline acetyltransferase, a marker of parasympathetic nervous function, shows transient increases during the development of acute right ventricular hypertrophy. The potential physiological importance of these changes prompted us to examine a clinically more relevant model of slowly progressive ventricular hypertrophy. Application of a loose band around the pulmonary artery of weanling guinea pigs resulted in a growth-related progressive right ventricular pressure overload. Right ventricular weight-to-body weight ratio was increased significantly and progressively at 9 and 18 weeks in banded animals (0.92 +/- 0.05 and 1.31 +/- 0.11 mg/g, respectively, p less than 0.01) compared with sham-operated controls (0.55 +/- 0.02 and 0.59 +/- 0.01 mg/g, respectively) but showed no further gain at 27 weeks (1.41 +/- 0.10 mg/g). Activities of tyrosine hydroxylase and dopamine beta-hydroxylase remained unchanged in all experiment groups, while right ventricular contents of norepinephrine in banded animals at 18 and 27 weeks exhibited sustained and progressive increases (2.45 +/- 0.11 and 3.40 +/- 0.19 micrograms/right ventricle, respectively) over controls (1.80 +/- 0.13 and 2.40 +/- 0.22 micrograms/right ventricle, respectively, p less than 0.01). The activity of choline acetyltransferase was markedly elevated in banded animals at 18 weeks (32.6 +/- 2.7 nmol/hr/right ventricle) but returned to baseline by 27 weeks (22.8 +/- 1.4 nmol/hr/right ventricle).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886235 TI - Validity of 5-aminolevulinate dehydratase activity (5-ALAD) for the discrimination of alcoholics and nonalcoholics with chronic liver disease. AB - Alcohol consumption decreases erythrocyte 5-ALAD activity. Our aim was to assess the diagnostic value of 5-ALAD in discriminating alcoholics from nonalcoholics among patients with chronic liver disease and to find the combination of 5-ALAD and other clinical chemical tests that best differentiates these two groups. Measurements of erythrocyte 5-ALAD activity by fluorometry and 10 other biochemical tests were performed in 205 subjects with biopsy-verified liver damage (88 alcoholics, 117 nonalcoholics). The highest six Chi-square (chi 2) test values out of the 11 tests performed were diagnostically evaluated individually and in combinations of two to five tests, according to the number of positive findings. Our results show that 5-ALAD provides the highest efficiency as an individual test, while combinations of three tests where 5-ALAD is involved, especially the combination of 5-ALAD, gamma-glutamyltransferase and mean corpuscular volume of erythrocytes, seem to be the best test combinations for discriminating alcoholics from nonalcoholics among patients with chronic liver diseases. PMID- 2886233 TI - Differential time-course of induction of rat liver gamma-glutamyltransferase and drug-metabolizing enzymes in the endoplasmic reticulum, Golgi and plasma membranes after a single phenobarbital injection. Evaluation of protein variations by two-dimensional electrophoresis. AB - This study was conducted to follow as a function of time the activity of gamma glutamyltransferase in the various membranes of rat liver cells after a single dose of phenobarbital (PB) (75 mg kg-1 body weight). Gamma-glutamyltransferase induction was maximal 24 h after PB treatment in both the rough endoplasmic reticulum and the plasma membranes. This pattern of induction differed from that of some drug metabolizing enzymes. While total cytochrome P-450 content was enhanced mainly in endoplasmic reticulum until 48 h after PB treatment, UDP glucuronosyltransferase activity was not greatly altered by PB under the same conditions. The comparison of two-dimensional electrophoretic polypeptide profiles of each subcellular membrane isolated from control and phenobarbital treated rats revealed important variations induced by PB. In plasma membranes, the heaviest subunit (apparent Mr = 60 x 10(3)) of hepatic gamma glutamyltransferase was provisionally identified as a collection of polypeptide which differ only by their pI. The concentration of these polypeptides was smaller in the endoplasmic reticulum where they were of lower apparent molecular mass. This suggests that the gamma-glutamyltransferase precursor is already processed at the level of the endoplasmic reticulum but it is still not completely mature or glycosylated. Five days of continuous PB treatment induced by appearance of new gamma-glutamyltransferase isoforms in plasma membranes. We demonstrate that after a single injection of PB, gamma-glutamyltransferase activity increases simultaneously with some drug-metabolizing enzymes, such as total cytochrome P-450 but not with others, such as UDP-glucuronosyltransferases. PMID- 2886237 TI - Choroideremia: close linkage to DXYS1 and DXYS12 demonstrated by segregation analysis and historical-genealogical evidence. AB - Linkage studies using restriction fragment length polymorphisms were conducted in the X-linked disorder, choroideremia, designated TCD for Progressive Tapeto Choroidal Dystrophy. Previously demonstrated close linkage with locus DXYS1 was confirmed (lod 11.44 at 0 recombination distance). In addition, locus DXYS12 was found to be closely linked with TCD (lod 3.31 at 0 recombination distance). The disease mainly occurs in three large kindreds in remote Northern Finland. While formal genealogical proof is lacking, all presently living (more than 80 affected males and 120 carrier females) probably originate from a common founder couple born in 1644 and 1646, twelve generations ago. All 36 patients and 48 carriers tested from the three kindreds had the same haplotype (TCD/DXYS1, 11kb/DXYS12, 1.6kb). Given that at least 105 female meioses transmitting TCD have occurred since 1650 in these kindreds, extremely close linkage between TCD, DXYS1 and DXYS12 is suggested. The above haplotype is a very useful diagnostic tool in these TCD families. We suggest that our historical-genealogical approach to linkage analysis may be possible elsewhere in similar isolated populations. PMID- 2886236 TI - Activities of dipeptidyl peptidase II and dipeptidyl peptidase IV in mice with lupus erythematosus-like syndrome and in patients with lupus erythematosus and rheumatoid arthritis. AB - We examined the activities of peptidases in plasma and tissues of the New Zealand Black (NZB) mouse as an animal model of human systemic lupus erythematosus, and also in serum from patients with rheumatoid arthritis and systemic lupus erythematosus. Activities of dipeptidyl peptidase II (DAP II) and post-proline cleaving enzyme (PPCE) were increased, and dipeptidyl peptidase IV (DAP IV) activity was decreased in plasma and spleen of NZB mice, as compared with the control BALB/c mice. Likewise, the activity of DAP II was increased and that of DAP IV was decreased in serum of patients with rheumatoid arthritis and systemic lupus erythematosus. These results indicate the importance of hydrolytic enzymes in the pathogenesis of autoimmune diseases. PMID- 2886238 TI - The effect of beta-adrenoceptor blockers on the absorption and excretion of chlorothiazide in man. AB - The effect of beta-adrenoceptor blockers on the absorption and elimination of the diuretic chlorothiazide was studied in healthy subjects. A week of pretreatment with either pindolol (10 mg twice daily) or propranolol (80 mg twice daily) resulted in significant reduction in 36 h mean cumulative urinary recovery of chlorothiazide in two groups of six subjects compared with a control (untreated) group. A week of pretreatment with atenolol (100 mg daily) did not significantly alter 36 h cumulative urinary excretion in another group of six subjects. None of the beta-blockers significantly changed chlorothiazide half-life. It is suggested that the non-selective (as opposed to the cardioselective) beta-blockers reduce chlorothiazide absorption by the mechanism(s) discussed. PMID- 2886239 TI - Hypotensive response to atrial natriuretic factor in conscious renal hypertensive beagles. AB - The hemodynamic responses to i.v. infusion of 0.3 and 0.6 microgram/kg per min of human atrial natriuretic factor (hANF [102-126]) in intact, conscious, one kidney, perinephritic, hypertensive beagles were examined and compared with the responses in ganglionic-blocked dogs. Blood pressure and heart rate were not affected but plasma ANF-like immunoreactivity was increased by as much as 627%. After hexamethonium (20 mg/kg, i.v.) blockade, a dose-dependent hypotensive response of up to 29 mmHg with no change in heart rate was observed. It is concluded that the compensatory mechanisms of the neurally mediated baroreflex system masked the depressor actions of hANF. PMID- 2886240 TI - The effects of calcium antagonists on blood pressure and responses to alpha adrenoceptor agonists in hypertensive rabbits. AB - The effects of the calcium antagonists verapamil and nifedipine on mean arterial blood pressure, heart rate and pressor responses to a range of alpha-adrenoceptor agonists were examined in male normotensive New Zealand white rabbits and in rabbits with perinephritis hypertension. Verapamil and nifedipine caused a greater fall in mean arterial pressure in hypertensive compared to normotensive rabbits both when the fall was expressed as an absolute and as a percentage change. Effects on heart rate were similar in normotensive and hypertensive animals. Pressor responses to phenylephrine were attenuated by nifedipine and verapamil in normotensive and hypertensive rabbits. Pressor responses to alphamethyl noradrenaline were also attenuated by nifedipine, but pressor responses to BHT 920 were not significantly altered by either calcium antagonist in normotensive or hypertensive rabbits at the dose used. Thus the calcium antagonists had a greater effect on alpha 1 - than alpha 2-adrenoceptor mediated responses in both normotensive and hypertensive rabbits. Hypertensive animals showed an increased responsiveness to phenylephrine and alphamethyl noradrenaline but not BHT 920 compared to normotensives. This difference remained after treatment with both the calcium antagonists. PMID- 2886242 TI - Endocrine hypotheses for the etiology of premenstrual syndrome. PMID- 2886241 TI - Improving the response to gold or D-penicillamine by addition of sulphasalazine. A pilot study in 25 patients with rheumatoid arthritis. AB - In a 6-month open pilot study 25 patients with Rheumatoid Arthritis (RA) whose disease was refractory to Gold or D-Penicillamine (DPA) were given Sulphasalazine (SAS) in addition. Three patients withdrew because of nausea. Twenty-two patients who completed therapy showed significant improvement in clinical and laboratory measures of disease activity. PMID- 2886243 TI - Fetal adenoma of the thyroid. A common source for false-positive thallium 201/technetium-99m pertechnetate subtraction parathyroid scintigraphy. AB - The specificity of thallium/technetium imaging for the localization of parathyroid tumors has remained high. False-positive findings usually arise from an incorrectly perceived mismatch. In these case reports, false-positive findings resulted from the presence of intrathyroidal fetal adenomas. Benign thyroid adenomas appear to represent a common source of false-positive finding for parathyroid tumor in thallium/technetium imaging. PMID- 2886245 TI - The effect of various dose regimens of famotidine on basal nocturnal and meal stimulated gastric secretion. AB - The antisecretory profile of the H2-receptor antagonist famotidine was studied with various oral doses and regimens in 10 healthy volunteers with high basal acid output (greater than or equal to 5 mEq/hr). Doses included 10, 20, and 40 mg at 9 PM and 9 AM and also 40 mg at 9 PM only. In the 22 hours after the PM doses, overnight (midnight to 7 AM) basal acid secretion was evaluated. Daytime meal stimulated secretion was assessed at 7 AM, 12 noon, and 5 PM. Doses of 10, 20, and 40 mg inhibited fasting nocturnal basal secretion by 69%, 86%, and 83% to 94%, respectively (P less than 0.01). Meal-stimulated secretion at 7 AM (10 hours after administration) was inhibited by 28% and 39% (P less than 0.01) by only the 40 mg doses. The response to the 12 noon meal was inhibited by the 9 AM doses of 10, 20, and 40 mg by 45%, 75%, and 85%, respectively (P less than 0.01). The effect of a 40 mg dose given at 9 PM only had dissipated by breakfast (7 AM). The response to the 5 PM meal was suppressed by the 20 and 40 mg doses given at 9 AM by 22% and 35%, respectively (P less than 0.05). Suppression was present in only eight of the subjects after the 20 mg dose but in all 10 after the 40 mg dose. The effect on basal gastric aspirate pH values paralleled those seen on acid output. An association was found between mean plasma concentrations of famotidine and mean inhibition of meal-stimulated acid secretion. However, individual values may not be predictive. PMID- 2886246 TI - Carnitine acyltransferases and acyl-CoA hydrolases in human and rat liver. AB - The activities of carnitine acyltransferases and acyl-CoA hydrolases were determined in human and rat liver to establish the validity of extrapolating from studies on rats to human metabolism. In human liver, carnitine acetyltransferase activity was 10-14 times higher and carnitine octanoyltransferase 1.7-2.4 times higher than in rat liver, while carnitine palmitoyltransferase activity was similar in human and rat. Acetyl-CoA hydrolase and octanoyl-CoA hydrolase activities were lower in human (42-57%) than in rat liver, but palmitoyl-CoA hydrolase activity was similar in both species. The activity of citrate synthase was lower (44%) in human than in rat liver. The low citrate synthase activity and the high carnitine acetyltransferase in human liver suggest that in man acetylcarnitine might be more important as a vehicle for export of acetyl units from mitochondria than citrate. The high activity of carnitine acetyltransferase in human liver is consistent with the observation that acetylcarnitine is the predominant acylcarnitine excreted in diabetic ketosis in man. It is concluded that the rat may not be a valid model for carnitine metabolism in man, and that in human liver carnitine may have an important role in transfer of acetyl groups out of mitochondria and possibly also to extra-hepatic tissues. PMID- 2886247 TI - A critical assessment of antipsychotic drug monitoring. AB - Analytic problems associated with monitoring antipsychotic drug levels have largely been resolved. Despite the establishment of target values for some drugs, the clinical utility of such levels remains to be determined. PMID- 2886244 TI - Clinical pharmacokinetics of beta-adrenoceptor antagonists. An update. AB - The beta-adrenoceptor antagonists have been widely used clinically for over 20 years and their pharmacokinetics have been more thoroughly investigated than any other group of drugs. Their various lipid solubilities are associated with differences in absorption, distribution and excretion. All are adequately absorbed, and some like atenolol, sotalol and nadolol which are poorly lipid soluble are excreted unchanged in the urine, accumulating in renal failure but cleared normally in liver disease. The more lipid-soluble drugs are subject to variable metabolism in the liver, which may be influenced by age, phenotype, environment, disease and other drugs, leading to more variable plasma concentrations. Their clearance is reduced in liver disease but is generally unchanged in renal dysfunction. All the beta-adrenoceptor antagonists reduce cardiac output and this may reduce hepatic clearance of highly extracted drugs. In addition, the metabolised drugs compete with other drugs for enzymatic biotransformation and the potential for interaction is great, but because of the high therapeutic index of beta-adrenoceptor antagonists, any unexpected clinical effects are more likely to be due to changes in the kinetics of the other drug. Because satisfactory plasma concentration effect relationships have been difficult to establish for most clinical indications, and little dose-related toxicity is seen, plasma beta-adrenoceptor antagonist concentration measurement is usually unnecessary. The investigation of the clinical pharmacokinetics of the beta-adrenoceptor antagonists has added greatly to our theoretical and practical knowledge of pharmacokinetics and made some contribution to their better clinical use. PMID- 2886249 TI - Conference for young diabetics. PMID- 2886248 TI - Plasma immunoreactive somatostatin is elevated in diabetic ketoacidosis and correlates with plasma non-esterified fatty acid concentration. AB - In experimental diabetes and after the administration of beta-hydroxybutyrate and non-esterified fatty acids (NEFA), an increase in circulating immunoreactive somatostatin (IRS) has been described. Both ketones and NEFA are raised in diabetic ketoacidosis. Therefore, we decided to investigate 10 patients in diabetic ketoacidosis by measuring, on admission and throughout the initial 24 hours of therapy, circulating levels of IRS, beta-hydroxybutyrate, acetoacetate, triglycerides, blood glucose, pH and NEFA. Fluids and insulin were administered IV following a previously established protocol. Nine patients showed abnormally high levels of circulating IRS. When compared with a group of controlled insulin dependent diabetic patients, basal IRS was high (111 +/- 15 vs 28 +/- 3 pmol/l), and remained elevated for at least 24 h despite clear improvement of metabolic status. On admission we also found elevated levels of NEFA (1.04 +/- 0.2 mmol/l), triglycerides (4.7 +/- 1.1 mmol/l), beta-hydroxybutyrate (22.1 +/- 4mmol/l), and acetoacetate (4.8 +/- 1.1 mmol/l). A significant correlation was found initially between IRS and NEFA (p less than 0.01). We conclude that circulating IRS is high in most cases of diabetic ketoacidosis. The mechanism behind this hypersomatostatinaemia could be related to the abnormalities of lipid metabolism which occur in diabetic ketoacidosis. PMID- 2886250 TI - Therapy for chronic obstructive lung disease. AB - CAO is a chronic, degenerative disease of the lung that produces a number of serious physiologic abnormalities in respiratory function. It is progressive and, in general, responds poorly to medical therapy. Cigarette smoking is almost universally the cause of the disease, and stopping smoking clearly slows the progress of the disorder. Therapy is of marginal value at best in a substantial number of patients with this problem, and even in those who respond well, improvement in function is not great. A conservative approach to therapy is advised, but only when its value can be documented. As the illness progresses, chronic oxygen therapy in hypoxic patients may be of value in preventing or treating cor pulmonale. PMID- 2886251 TI - Antidiuretic responses to osmotic, ionic or volume stimulation of the brain in the unanesthetized toad, Bufo arenarum Hensel. AB - Single injections of 15 microliter of 1 M NaCl or 2M sucrose into the carotid system of normal unanesthetized toads induced a rapid and significant decrease of urine production. This appears to be the first report on the existence of a Verney-like phenomena in a non-mammalian vertebrate. This antidiuresis was blocked out in the hypophysectomized diencephalic lesioned animal. Concurrently, small volumes (4 microliters) of 1 M NaCl but not 2 M sucrose also induced antidiuresis when injected into the midbrain tegmentum of normal but not of hypophysectomized diencephalic lesioned toads. Larger volumes (6 microliters) of 2 M sucrose were needed to induce a similar antidiuresis in normals. Furthermore, even larger volumes (more than 8 microliters) of any of both solutions were able to induce oliguria in normal as well as in hypophysectomized toads. On the basis of these results, the following conclusion would be drawn: the brain of the toad is able to detect ionic and osmotic stimuli, these stimuli apparently affect different receptors in the brain, the antidiuresis initiated by these mechanisms is dependent on diencephalic integrity. PMID- 2886252 TI - Effects of two-thirds hepatectomy on sulfobromophthalein handling by the rat liver. AB - The modifications in the hepatic transport of sulfobromophthalein (BSP) were studied after partial hepatectomy (p.h.) in Wistar rats. The biliary excretion of BSP, injected i.v. at 150 mumol/kg, decreased in the early periods after p.h., with a disappearance of the choleretic effect induced by the dye in sham-operated animals. The impairment in the biliary BSP excretion corresponded to the conjugated fraction and was accompanied by a lowered glutathione S-transferase activity in the liver. PMID- 2886254 TI - Hyperphosphataemia and bone resorption in histamine injected laying hens. AB - The effects of histamine on bone resorption during eggshell formation, were studied. The study included the effect of histamine on the clearance of 45Ca and 32P from plasma, and on the release from the femur or uptake by the egg shell of 45Ca and 32P injected at the time of the first experiment or 10 hr prior to the experiment (experiment 2). Histamine led to a decrease in the disappearance rates of 45Ca and 32P, without any modification of the femur and egg shell levels. However, the increase in the amount of plasma 32P and the decrease in the 32P specific activity (SA) in bone, both elicited by histamine, argues in favour of the skeletal origin of hyperphosphataemia induced by histamine during egg shell formation. PMID- 2886253 TI - Metabolic effects and secretory properties of a radiation-induced transplantable rat insulinoma. AB - The metabolic effects and secretory properties of a radiation-induced transplantable insulinoma were examined in 16-17 week old NEDH rats. Subcutaneous subscapular implantation of tumour fragments resulted in hyperphagia, increased body weight gain, marked hyperinsulinaemia and severe hypoglycaemia, with the resulting death of the recipient by 27 days. Ultimate tumour size was 2.1 +/- 0.4 g (mean +/- SEM). At 3 days after transplantation, plasma glucose and insulin responses to intraperitoneal glucose, insulin, arginine and adrenaline were similar to control rats. At 20 days, plasma glucose concentrations of insulinoma bearing rats remained low throughout glucose tolerance tests, and insulin responsiveness to glucose stimulation was absent. 2-Deoxy-D-glucose produced only a small rise of glucose concentrations in tumour-bearing rats. Insulin sensitivity was not appreciably impaired at 20 days despite severe hyperinsulinaemia and hypoglycaemia. The ability of adrenaline and propranolol to suppress plasma insulin and raise plasma glucose concentrations was also retained. At 20 days, glucagon evoked a marked plasma insulin response with no change in plasma glucose concentrations. In contrast, arginine and glibenclamide failed to stimulate insulin above high basal concentrations. PMID- 2886256 TI - On the relation between basal and maximum metabolic rate in mammals. AB - Basal and maximum metabolic rates, measured by oxygen consumption, for 18 species of wild mammals have been obtained from a search of literature records. The mass exponent of the allometric regression equation for maximum metabolic rate is significantly higher than that for BMR (0.841 and 0.745, respectively; P less than 0.05) in the group of animals examined. No significant correlation between mass-independent basal and maximum metabolic rates has been found. These results do not support the 'aerobic capacity' model of the origin of endothermy. PMID- 2886255 TI - Involvement of the sympathetic nervous system in lipolytic activity in brown adipose tissue of cold acclimated rats. AB - In cold acclimated rats, in vitro, NE led to a significant increase in release of FFA and glycerol in denervated IBAT. In vivo, study of arteriovenous differences showed that the denervated BAT loses its full capacity to utilize FFA and glycerol released by NE. After denervation an increase of blood flow in Sulzer's vein was observed. This effect appeared immediately after intervention whereas the effect on fat metabolism appeared later. In cold acclimated rats, the sympathetic nervous system appears to be an important regulator of fatty acid metabolism in BAT. PMID- 2886257 TI - Effect of dietary carbohydrate source on soluble protein glucose concentration and enzyme activity (aldolase) of European eels (Anguilla anguilla L.). AB - This study was undertaken to determine the influence of dietary carbohydrate sources: wheat meal, bread meal, soluble corn starch, native potato starch and sorghum meal, on soluble protein, enzyme activity (aldolase) and glucose concentration in muscle and liver of European eels (Anguilla anguilla). There was less soluble protein in both muscle and liver of eels fed 30% wheat meal or bread meal than the other experimental groups. However, eels fed 30% bread meal or soluble corn starch had a higher glucose concentration in muscle and liver than the other experimental groups. High enzyme activity (aldolase) was found in the liver of eels fed 30% wheat meal, bread meal or soluble starch. PMID- 2886258 TI - Cold acclimation in food-restricted rats. AB - Food intake, body weight and brown adipose tissue (BAT) mass and composition of rats exposed at 6 degrees C either with food ad libitum or food-restricted were compared with those of rats in the thermoneutral zone, with food ad libitum. Cold acclimation with food ad libitum increases food intake and prevents body weight gains. IBAT (interscapular BAT) increases its mass and changes its composition after 3 weeks of cold exposure. Cold acclimation with food restriction produces a progressive decrease in body weight. IBAT mass increases after 3 weeks but changes in composition occur sooner. It is concluded that the overfeeding that accompanies cold acclimation is not necessary for non-shivering thermogenesis in BAT. PMID- 2886259 TI - Coronary ligation reduces maximum sustained swimming speed in Chinook salmon, Oncorhynchus tshawytscha. AB - The maximum aerobic swimming speed of Chinook salmon (Oncorhynchus tshawytscha) was measured before and after ligation of the coronary artery. Coronary artery ligation prevented blood flow to the compact layer of the ventricular myocardium, which represents 30% of the ventricular mass, and produced a statistically significant 35.5% reduction in maximum swimming speed. We conclude that the coronary circulation is important for maximum aerobic swimming and implicit in this conclusion is that maximum cardiac performance is probably necessary for maximum aerobic swimming performance. PMID- 2886260 TI - The effects of cold acclimation on electrocardiogram parameters in five species of turtles. AB - The effects of thermal acclimation at 25 or 5 degrees C on electrical activity in the heart were investigated in Pseudemys scripta, Terrapene carolina, Chrysemys picta marginata, Chrysemys picta dorsalis, Chelydra serpentina, and Sternotherus odoratus. The durations of the QRS complex and P-R, R-T and R-R intervals were found to increase with decreasing body temperature in all animals tested. The amplitudes of the P and T waves and QRS complex were dependent upon both acclimation temperature and test temperature. Differences between acclimation groups in the change in QRS amplitudes between 20 and 0 degrees C were statistically significant for all species. PMID- 2886261 TI - A comparison of energy substrates and reproductive patterns of two anurans. Acris crepitans and Bufo woodhousei. AB - The seasonal pattern of carcass, liver and ovary lipid and liver non-lipid mass was examined in the cricket frog, Acris crepitans, and Woodhouse's toad, Bufo woodhousei. Reproductive patterns were also studied. The over-winter reduction of body lipid and liver non-lipid material was attributed to metabolism in Acris crepitans. Male, but not female, Bufo woodhousei exhibited seasonal variation in lipid stores that was attributable to metabolism. Females, but not males, showed seasonal variation in liver non-lipid mass and quantified liver glycogen. Females of both species mobilized body lipid during the period of ovarian development; however, an inverse relationship between fatbody mass and ovary mass was evident for Acris, only. Female Acris crepitans depleted all ovarian follicles prior to brumation; however, Bufo woodhousei retained enlarged follicles throughout the year. Variation in metabolic substrate use between species was related to the differences in reproductive patterns exhibited by the two anurans. These variations in reproductive strategy represent adaptations that enhance the survivability of different species in dissimilar habitats. PMID- 2886263 TI - The status of the study of invertebrate neurons in tissue culture--phylum Arthropoda. AB - 1. Neurobiological studies employing tissue culture are discussed for all invertebrate organisms in phylum Arthropoda and above. Only arthropod species have been investigated in these studies. 2. The members of phylum Arthropoda utilized were Periplaneta, Locusta, Drosophila, and Schistocerca. 3. Some of the initial studies of nerve cells in tissue culture were performed with Periplaneta and Drosophila; these studies were primarily concerned with differentiation, growth and development. 4. Cultured neurons from cockroach and locust have been used in pharmacological investigations of neurotransmitter receptors. 5. Embryos of the grasshopper Schistocerca were cultured in series of developmental studies related to axon guidance and peripheral nerve formation. 6. Recent studies with Drosophila neurons in vitro have applied a genetic approach to the investigation of molecular properties and function of the axonal sodium channel. 7. An overall view of neuronal tissue culture of invertebrates and analysis of the various areas of research is presented. PMID- 2886262 TI - Red blood cell potassium types of angora goats (Capra hircus). AB - Two distinct K phenotypes with normal frequency distribution curves were found and identified as low (LK) and high (HK) potassium types in the red blood cells of 748 Angora goats. The division between the two types was arbitrarily assigned at 24.9 meq/l. Of the two KRBC level types; the LK type was predominating, its curve showed evidence of leptokurtosis and was negatively skewed. The HK type had a curve slightly mesokurtic and the population was normal with respect to skewness. PMID- 2886264 TI - Low-molecular-weight zinc-binding ligand: a regulatory modulator for intestinal zinc transport. AB - 1. In the last two decades, vast numbers of studies on the zinc nutriture of animals and man have been made. However, the biochemical and physiological events in controlling zinc nutrition are still poorly understood. This report concerns the progress made toward understanding the intestinal zinc absorption and secretion mechanisms. 2. Evidence is accumulating that zinc absorption is a facilitated diffusion while zinc secretion is an active transport. 3. It is known that a low molecular weight zinc-binding ligand (LMW-ZBL) is a key regulator of intestinal zinc absorption, possibly a carrier molecule across the intestinal mucosal cells. Some high molecular weight zinc-binding ligands also appear to be involved in regulating intestinal zinc transport. 4. The identity of the LMW-ZBL is a matter of controversy and its specific role in regulating intestinal zinc transport is not well defined. 5. According to the available literature, no systemic investigations have been made to elucidate the intestinal zinc transport mechanisms, and much more information is needed to fully understand them. PMID- 2886266 TI - Estimates of plasma, packed cell and total blood volume in tissues of the rainbow trout (Salmo gairdneri). AB - 1. Total blood volume and relative blood volumes in selected tissues were determined in non-anesthetized, confined rainbow trout by using 51Cr-labelled trout erythrocytes as a vascular space marker. 2. Mean total blood volume was estimated to be 4.09 +/- 0.55 ml/100 g, or about 75% of that estimated with the commonly used plasma space marker Evans blue dye. 3. Relative tissue blood volumes were greatest in highly perfused tissues such as kidney, gills, brain and liver and least in mosaic muscle. 4. Estimates of tissue vascular spaces, made using radiolabelled erythrocytes, were only 25-50% of those based on plasma space markers. 5. The consistently smaller vascular volumes obtained with labelled erythrocytes could be explained by assuming that commonly used plasma space markers diffuse from the vascular compartment. PMID- 2886265 TI - Relationships between morphological parameters in birds with different flying habits. AB - 1. Data on morphological and physiological parameters from 346 species of birds were collected from diverse sources. 2. The observed relationships among some pairs of variables showed differences between the five flight styles into which the studied birds were classified. 3. The characteristic kind of flight for each species is related to four easily obtainable non-invasive parameters: body weight (BW), wing area (WA), wing span (WS) and boyd length (BL). 4. Wing-loading index (BW2/3/WA) gives the most effective variable to describe the flying habits of any species. PMID- 2886267 TI - Thermal freedom of Graomys griseoflavus in a seasonal environment. AB - 1. Thermal freedom, defined as the physiological potential to make full spatiotemporal use of the seasonal thermal macroclimate, was assessed in Graomys griseoflavus, a cricetid rodent inhabiting the Chaco Province in Argentina. 2. The extent of the physiological thermal range (58 degrees C) was larger than the seasonal thermal range (30-50 degrees C), favoring Graomys resistance to low winter temperatures. The upper physiological thermal limit was almost coincident with the highest extreme of summer temperatures. 3. Graomys thermal freedom is facilitated by a high evaporative water loss, high metabolic capability, wide thermal neutral zone and a 4 degrees C lability of body temperature. 4. Behavioral responses (thermal avoidance) are utilized by this species, but with no apparent loss in thermal freedom. PMID- 2886268 TI - Effect of cage density and rank in peck order on brain regional monoamines in adult male Coturnix coturnix japonica. AB - 1. In adult male Coturnix coturnix japonica neither norepinephrine (NE) nor serotonin (5HT) in various brain regions were affected by caging density (174 cm2 8/cage; 348 cm2-4/cage; 696 cm2-2/cage). Dopamine (DA) in diencephalon was elevated in high density cages. 2. Peck order rank was assigned on the basis of feather distribution on head, neck and back and lesions on head and back. 3. Upper strata peck order rank was associated with significantly lower levels of brain regional NE and DA compared to lower strata peck order rank. 4. Peck order rank did not affect brain regional 5HT. 5. The results indicate significant individual behavioral-neuroendocrine interaction leading to reproductive dysfunction. PMID- 2886269 TI - Effects of pH and/or calcium-enriched freshwater on plasma levels of vitellogenin and Ca2+ and on bone calcium content during exogenous vitellogenesis in rainbow trout (Salmo gairdneri). AB - 1. Three year old rainbow trout were exposed to low pH (5.1) and/or calcium enriched (1.52 mM) freshwater for 10 weeks. 2. Plasma was collected periodically from individually-marked fish for analysis of total calcium and alkaline-labile phosphate (vitellogenin). 3. After the last sample gonadosomatic and hepatosomatic indices were measured and the caudal vertebrae centra were analysed for total calcium content. 4. Female trout exposed to calcium-enriched freshwater had increased plasma vitellogenin levels compared to females in soft water, whereas there was a tendency for low pH to decrease plasma vitellogenin in these fish. 5. The gonadosomatic and hepatosomatic indices were reduced in female trout exposed to acidified water. 6. There was no evidence of bone demineralization in trout exposed to low pH. PMID- 2886270 TI - Alcian blue-alcian yellow mapping of neurosecretory cells in the central nervous system of the salt marsh pulmonate snail Melampus bidentatus. AB - 1. The neurosecretory system of the primitive ellobiid Melampus bidentatus (Pulmonata: Basommatophora) was investigated using Alcian blue-Alcian yellow histochemistry. 2. Putative neurosecretory cells within the central ganglia were distinguished by the criteria of cell size, position, and staining reaction. 3. The cerebral ganglia, with attached lateral lobes, contained the greatest diversity of neurosecretory cell types (at least seven), including single cells and cell clusters ranging from two to 40 cells. 4. Four neurosecretory cell types were identified in the parietal and visceral ganglia, two in the pedal ganglia, and one each in the buccal and pleural ganglia. 5. Neurosecretory system homology among pulmonate gastropods is suggested by the close similarity of the Melampus AB/AY cell map to those reported in the literature for two limnic basommatophorans and for four terrestrial stylommatophorans. PMID- 2886271 TI - Calcium and magnesium dependence of spontaneous and evoked afferent neural activity in the lateral-line organ of Xenopus laevis. AB - 1. Rates of spontaneous and mechanically evoked neural impulses from the Xenopus laevis lateral line were compared in the presence of calcium and/or magnesium or in the absence of either divalent cation, bath-applied to the synaptic side of the mechanoreceptors. 2. Spontaneous activity and total activity during mechanical stimulation decreased with increasing calcium or magnesium concentration. 3. Activity during stimulation minus spontaneous activity increased with increasing calcium concentration and decreased with increasing magnesium concentration. 4. At constant divalent cation concentration, increasing calcium/magnesium increased total stimulated activity minus spontaneous activity, while spontaneous activity remained essentially constant. 5. Membrane charge screening and mass action of divalent cations at voltage-dependent cation channels are hypothesized to account for the effects observed. PMID- 2886273 TI - Somatostatin inhibition of growth hormone secretion in an adult bird: the domestic fowl. AB - 1. The intravenous (i.v.) infusion of somatostatin (SRIF, 1.0 microgram/kg per min) promptly (within 5 min) reduced the growth hormone (GH) concentration in the plasma of conscious adult chickens. 2. The GH concentration progressively declined throughout a 60-min period of SRIF infusion, but was dramatically increased above pre-infusion levels within 5 min of SRIF withdrawal and maintained at an elevated level for at least 30 min afterwards. 3. Sodium pentobarbitone-anaesthesia lowered the basal GH concentration to levels comparable with those in conscious birds infused with SRIF. When administered to anaesthetized birds, exogenous SRIF was unable to further reduce the GH concentration and unable to induce 'rebound' GH release. 4. While thyrotropin releasing hormone (TRH, 10 micrograms/kg) increased the GH concentration in both conscious and anaesthetized birds, only the GH response in the anaesthetized birds was diminished by SRIF infusion. 5. Rebound GH secretion following the termination of SRIF infusion was observed in both conscious and anaesthetized birds injected with TRH. 6. These results demonstrate that SRIF can inhibit basal and TRH-stimulated GH secretion in adult domestic fowl and indicate that anaesthesia disrupts the normal control of GH releases. PMID- 2886272 TI - Caecal size and function in the rock elephant shrew Elephantulus myurus (Insectivora, Macroscelididae) and the Namaqua rock mouse Aethomys namaquensis (Rodentia, Muridae). AB - 1. The relative size of the digestive organs and the function of the caeca of an insectivorous elephant shrew Elephantulus myurus (Macroscelididae) and of a herbivorous rodent Aethomys namaquensis (Muridae) were compared. 2. Both species had similar body mass but A. namaquensis had a significantly heavier total digestive tract, full stomach, and caecum and a longer large intestine and caecum than E. myurus. 3. Both species had similar total volatile fatty acid (VFA) concentration and VFA % composition although A. namaquensis had a significantly higher % of n-butyric acid. Both had a similar caecal NH3-N concentration. 4. The presence of a functional caecum in E. myurus supports the view that Macroscelididae have evolved from ancestral herbivores and not from insectivores. PMID- 2886274 TI - Metabolic and thermoregulatory consequences of social behaviors between Microtus townsendii. AB - 1. Townsend voles responded to each other by raising their core temperatures. 2. Increments of temperature increases that accompanied hostile reactions between voles, were proportional to the intensity of the behavioral displays. 3. Amicable behaviors (huddling) were also associated with higher body temperatures that were proportional to group size. 4. Huddling voles conserved metabolic energy expenditure by reducing their metabolic rates and thermal conductances. 5. Such conservation required 1 or more days of amicable behavior to develop, and to be reversed. 6. The degree of metabolic rate reduction that accompanied amicable huddling behavior and the associated reduction of thermal conductance was independent of group size. PMID- 2886275 TI - Development of changes in cation content of muscles from the 129 ReJ dystrophic mouse. AB - 1. Muscle cation levels have been measured in severely affected and relatively unaffected muscles of dystrophic mice (129 ReJ strain) compared to control animals at various ages. 2. Muscle calcium levels were found to be elevated in the severely affected gastrocnemius muscles only at a late stage of the disease, calcium levels in mildly affected triceps muscles were unaffected. 3. Muscle sodium levels were elevated in both triceps and gastrocnemius muscles at all ages studied. 4. Muscle magnesium and potassium contents showed similar changes, being significantly reduced in the gastrocnemius from the time of development of the first signs of weakness (i.e. 3-5 weeks of age), this decrease becoming more marked with increasing age and showing a less marked, but significant, change in the triceps muscle at a later stage of the disease. PMID- 2886277 TI - Stimulation of renal phosphate secretion in the stenohaline freshwater teleost: Carassius auratus gibelio Bloch. AB - 1. Renal excretion of phosphate in the Prussian carp was modulated by tubular reabsorption and tubular secretion. 2. Under the conditions of an i.v. phosphate load during which the plasma concentration of phosphate was doubled, 65% of the phosphate load was excreted by the kidney, mainly by tubular secretion. 3. The renal clearance of PAH markedly exceeded the clearance of polyfructosan which could be used for the measurement of the GFR. 4. A transport maximum for tubular PAH secretion was reached at plasma concentrations of about 250 mumol/l. PMID- 2886276 TI - Age dependence of somatostatin levels and somatostatin binding in the rat brain. AB - 1. Somatostatin-like immunoreactivity (SLI) and 125I-Tyrl-somatostatin binding were measured from the brains of rats aged 1, 8 and 18 months. 2. Somatostatin binding was reduced in the striatum, frontal cortex, hypothalamus and hippocampus of the 8-month-old rats compared to the 1-month-old group. 3. Somatostatin binding was reduced in the striatum, frontal cortex and hippocampus of the 18 month-old rats compared to the 1-month-old group. 4. The reduction (40%) was most striking in the frontal cortex. 5. In no area of the brain did changes in SLI differ significantly between the different age groups. PMID- 2886278 TI - Leukocyte numbers during the humoral and cell-mediated immune response of Japanese quail after microwave irradiation in ovo. AB - 1. Coturnix coturnix japonica eggs were exposed to 2.45-GHz continuous wave microwave radiation at an incident power density of 5 mW/cm2 (SAR = 4 mW/g) during the first 12 days of embryogeny. After hatching, leukocyte differential changes were measured in response to an injection with Alectoris graeca chukar red blood cells (CRBC) and in response to a phytohemagglutinin (PHA) injection in irradiated and nonirradiated (sham) quail of both sexes. 2. Microwave irradiation did not affect anti-CRBC hemagglutinin titers, PHA-evoked dermal swelling or leukocyte numbers and percentages. 3. In both the irradiated and sham irradiated males, lymphocyte percentages decreased while heterophil percentages increased after CRBC or PHA injection. 4. In ovo irradiation with microwaves did not alter the time course of either a humoral immune response or a cell-mediated immune response in Japanese quail. PMID- 2886279 TI - Basic haematological values in carnivores--II. The Felidae. AB - 1. Basic haematological values in 34 animals of eight carnivorous species are reported. 2. In four Northern lynxs (Lynx lynx lynx), two male and two female animals, the mean values are given: erythrocyte counts 8.51 X 10(12)/l, haematocrit 0.392/l, haemoglobin content 148.0 g/l and leukocyte count 7.92 X 10(9)/l. 3. In six male pumas (Puma concolor missolensis) the mean values estimated are: erythrocyte count 9.35 X 10(12)/l, haematocrit 0.43/l, haemoglobin content 163.9 g/l and leukocyte count 7.73 X 10(9)/l. Individual values in one female puma are also given. 4. In six jaguars (Panthera onca), three male and three female animals, the mean values are given: erythrocyte count 8.27 X 10(12)/l, haematocrit 0.37/l, haemoglobin content 137.1 g/l and leukocyte count 15.15 X 10(9)/l. 5. Only individual values are reported in one clouded leopard (Neofelis nebulosa), in one leopard (Panthera pardus saxicolor), in one Corbett's tiger (Panthera tigris Corbetti) and in one Altaic tiger (Panthera tigris Altaica). 6. In four lions (Panthera leo leo), two male and two female animals, the mean estimated values are: erythrocyte count 10.14 X 10(12)/l, haematocrit 0.462/l, haemoglobin content 159.0 g/l and leukocyte count 11.05 X 10(9)/l. In six female cheetahs (Acinonox jubatus jubatus) the mean values estimated are: erythrocyte count 7.86 X 10(12)/l, haematocrit 0.373/l, haemoglobin content 142.8 g/l and leukocyte count 8.65 X 10(9)/l. For three male cheetahs only individual values are reported. 8. All results achieved are compared with those abstracted from the literature and discussed. PMID- 2886280 TI - Blood volume and red cell space in tissues of the rainbow trout, Salmo gairdneri. AB - 1. Whole body blood volume and red cell space of 22 tissues were measured in unanesthetized rainbow trout at 4, 12, 30, 60, 150 and 240 min after dorsal aortic injection of 51Cr-labeled red blood cells. 2. Apparent blood volume decreased during the initial 30 min after injection and increased thereafter. At 240 min the blood volume was 33.5 +/- 3.1 ml/kg body wt. 3. Tissue red cell space varied as a function of the interval between labeled red cell injection and tissue collection. Red cell space was highest in spleen followed by heart, kidney and liver. Lowest red cell spaces were found in stomach and red and white skeletal muscle. 4. Variability in blood volume and tissue red cell space over time suggests that caution should be exercised in the design of experiments that employ indicator dilution measurements to measure vascular volumes. PMID- 2886281 TI - Cortisol-induced hematologic and immunologic changes in channel catfish (Ictalurus punctatus). AB - 1. Intravenous injections of physiologic doses of cortisol resulted in both hematologic and immunologic changes in channel catfish peripheral blood leucocytes. These changes mimicked those seen when catfish were acutely stressed by handling and transport. 2. Eighteen hours after the administration of cortisol, decreases in the number of circulating lymphocytes and concomitant increases in the number of circulating neutrophils were observed, i.e. to the same levels seen previously in stressed fish. 3. Functional analysis of peripheral blood leucocytes from cortisol-injected fish indicated that the remaining lymphocytes were no longer capable of responding to mitogenic stimuli. 4. This suppression of mitogenic stimuli was not seen when peripheral blood leucocytes were cultured in vitro with physiologic doses of cortisol. 5. This latter observation suggests that the cortisol alone was probably not directly responsible for the loss of responsiveness but possibly acted in vivo as an initiator of other events that eventually resulted in the observed immunosuppression. PMID- 2886282 TI - On calculating concentrations of "HCO3" from pH and PCO2. AB - 1. As used in the Henderson-Hasselbalch equation, [HCO3], [CO2] and pH may all be variously defined; values of pK'1 must be chosen accordingly. 2. In common usage, "HCO3" may include CO3, carbamate, various ion pairs and possibly other bound CO2, as well as free HCO3 ions. 3. pH measurements may be systematically affected by the choice of standard buffers and by proteins and blood cells, and the errors in pH may be pH-dependent. 4. According to how it is expressed, the solubility coefficient for CO2 (S) may be influenced by sample water content, proteins and lipids. However, it need not feature in the calculation. 5. pK'1 is often found to decrease with increasing pH. This may be partly due to inclusion of CO3 and carbamate, but not of H2CO3.HCO3-, in "HCO3" and partly, perhaps, to errors in pH measurement. 6. To the extent that pH measurements are reliable, concentrations or activities of true HCO3 are calculable from pH and PCO2, but, if pH measurements are likely to be systematically erroneous, it may be preferable to define "HCO3" as "total bound CO2" and to base pK'1 on gasometric or titrimetric determinations of that. PMID- 2886283 TI - Protein nutrition in the alligator. AB - 1. Fourteen different protein-containing diets were fed to small alligators. Their rates of digestion and their nutritional values were determined by following changes in free amino acids in the plasma. 2. Fish, chicken and nutria were digested rapidly and all their component essential amino acids disappeared quickly and at the same rate. When given in the dry, fat-free form the amino acids were released and assimilated about 50% faster than when fat was included. 3. None of the isolated proteins tested (casein, gelatin, edestin, gliadin, corn gluten and soy) proved nutritionally adequate and all but gelatin digested slowly and incompletely. 4. One diet compounded of salts, vitamins and mixed commercial animal products was tested. It showed promise but it was lacking in methionine and isoleucine. 5. It was concluded that dry, powdered, preparations from whole animals could prove a satisfactory, stable diet for alligator husbandry. 6. Prolonged force-feeding of an animal diet increased the percent of nitrogen excreted as NH3 over that excreted in urates. PMID- 2886284 TI - Blood changes in Bufo cognatus following acute heat stress. AB - 1. Various blood constituents were measured in an attempt to identify the effects of exposure of Great Plains toads to the critical thermal maximum (CTmax) and determine the time course of the onset of and recovery from these effects. 2. Tests for generalized tissue damage including serum glutamic-oxalacetic and glutamic-pyruvic transaminases (SGOT, SGPT), total protein and blood urea nitrogen (BUN) were unaffected by acute thermal stress. 3. Hematocrit, erythrocyte number, mean cell volume and hemoglobin concentration were also unchanged. 4. Blood glucose, lactic acid and creatine phosphokinase (CPK) levels all increased significantly. 5. Blood pH, PO2 and [HCO3-] also increased with acute heat stress while PCO2 decreased. 6. Long-term exposure to temperatures near the CTmax may cause severe tissue damage. Acute thermal stress does not appear to cause damage other than the short-term, reversible effects of strong physical exercise. PMID- 2886285 TI - Pyrogens fail to produce fever in the leopard tortoise Geochelone pardalis. AB - 1. The body temperature of seven tortoises, Geochelone pardalis, was measured in a thermal gradient chamber, by indwelling thermocouples, after injection of various pyrogens. 2. The tortoises regulated their body temperature by moving in the chamber. 3. The tortoises did not develop fever in response to any of the pyrogens we tested. 4. The results support the contention that fever in reptiles is not ubiquitous. PMID- 2886286 TI - Haematological values during normal reproduction of the maternal and the fetal rabbit. AB - 1. Haematological values of non-pregnant/non-lactating, pregnant as well as lactating rabbits and 28-day-old fetuses were measured. 2. The haemoglobin content in does decreased during the observed periods from 122 +/- 8 g/l to 100 +/- 11 g/l. In 28-day-old fetuses it was 85 +/- 0 g/l. 3. The erythrocyte count in 28-day-old fetuses was 2.4 X 10(12)/l. In the does, the erythrocyte count was 5.2 X 10(12)/l in week 4 of gestation. The erythrocyte volume in fetuses was about 45% higher than that of the doe. 4. In fetuses the leucocyte count was approximately one ninth that of the mother in week 4 of gestation (0.41 +/- 0.08 X 10(9)/l vs 3.8 +/- 0.4 X 10(9)/l). PMID- 2886287 TI - Calcium in the toad (Bufo marinus) cornea: binding by the stroma. AB - 1. The Ca concentration in the toad (Bufo marinus) cornea was 2.6 mmol/kg wet wt compared at 1.0 mmol/l in the bathing aqueous humor and 2.8 mmol/kg wet wt in the separated corneal stromal layer. Cell Ca content was calculated to be about 1.8 mmol/kg wet wt. 2. About 80% of the total Ca appears to be sequestered or bound to tissue components most of which (68% of the total) is associated with the stroma (2.2 mmol/kg wet wt stroma). 3. About 85-90% of the Ca in the stroma is readily exchangeable with external 45Ca. 4. The loss of accumulated 45Ca from the stroma was measured in vitro. This efflux of the isotope was enhanced by multivalent ions and was greatest when Ca2+ or La3+ was present in the external media. Other alkaline earth metal ions were not as effective. The relative effectiveness of this displacement of 45Ca was Ca = La greater than Sr greater than Ba greater than Mg. 5. The results suggest that the Ca2+ is bound by the amphibian stroma at sites that have a preference or specificity for this divalent ion as compared to the other alkaline earth metals. 6. The possible functional role of this bound Ca is discussed. PMID- 2886288 TI - Changes in the blood and the bone marrow picture of the Pharaoh quail (Coturnix coturnix Pharaoh) chicks as a manifestation of adaptation to postembryonal life. AB - 1. The aim was determination of the rate of adaptation of the respiratory and defence functions of the blood and bone marrow of quail chicks. 2. In the early post-hatching period, enhanced haemoglobin synthesis is the mechanism adapting the bird to the rich oxygen conditions beyond the egg. 3. In 2-week-old chicks, the increased respiratory function of the blood is associated with a parallel rise of the erythrocyte count and haemoglobin content. 4. The defence mechanisms of the chick in the first days after hatching are mainly connected with a high content of heterophilic granulocytes and in older chicks with a rising lymphocyte count. PMID- 2886289 TI - Relationship between length-tension relation and 20,000 dalton myosin light chain phosphorylation in guinea-pig taenia caeci. AB - 1. Relationship between length-tension relation and phosphorylation of 20,000 dalton myosin light chain (LC20) in guinea-pig taenia caeci was investigated. 2. At in situ length (Lb), a good linear correlation was obtained between isometric tension and LC20 phosphorylation in high-K+-stimulated muscle. 3. In 100 mM K+ stimulated muscle, the active tension decreased at muscle lengths other than Lb, but no significant decrease in degree of LC20 phosphorylation was observed. 4. These results suggest that in guinea-pig taenia caeci, the major portion of the decrease in active tension at muscle lengths other than Lb is not due to a decrease in degree of activation. PMID- 2886291 TI - The renal circulation of conscious rabbits. AB - 1. The renal circulatory instability that some believe is inherent in rabbits was studied. 2. In five, conscious rabbits, glomerular filtration rate (GFR) averaged 4.2 +/- 0.6 ml/min/kg body wt after 1 hr, but changed to an overall average of 3.5 +/- 1.5 ml/min/kg wt after 3 hr. 3. Between-measurement coefficient of variation for GFR was more than 30% for three rabbits and 10% or less for two. 4. Renal blood flow (RBF) was even more variable. 5. The renal circulatory instability may be associated with differences in sympathetic activity by mechanisms not existing in other mammals. PMID- 2886290 TI - Peptic erosion of gastric mucus in the rat. AB - 1. The effect of pepsin on the loss of mucus glycoprotein from the gastric epithelial mucus layer was studied in the rat. 2. Pepsin was instilled into the gastric lumen, and luminal contents were subsequently assayed. 3. Glycoprotein loss increased with luminal pepsin, up to a concentration of 1 mg pepsin/ml. 4. Luminal glycoprotein had a molecular size distribution intermediate between subunit, and native mucus glycoprotein of the epithelial mucus layer. 5. Incubation of gastric epithelial scrapings with pepsin demonstrated that insoluble, native mucus glycoprotein was rapidly degraded to soluble glycoprotein of similar molecular size distribution to that found in vivo in the lumen. PMID- 2886292 TI - The gamma-glutamyltranspeptidase of Trypanosoma cruzi. AB - Trypanosoma cruzi epimastigotes show gamma-glutamyltranspeptidase activity which has characteristics significantly different than the mammalian enzyme. The protozoan enzyme is localized in the cytosolic fraction, it has a Km of 1.6 mM and a Vmax of 17.4 nmol/min/mg protein with L-gamma-glutamyl-p-nitroanilide as gamma-glutamyl donor, and an optimun pH range from 7.5 to 8.0. The best amino acid acceptors were L-histidine, L-asparagine, L-aspartate, L-glutamate and L proline, but L-glutamine was a very poor acceptor. The enzyme was very sensitive to inhibition by 6-diazo-5-oxo-L-norleucine (k2 = 4.0 X 10(5)/M per min) and O diazo-acetyl-L-serine (k2 = 1.1 X 10(4)/M per min). Phenobarbital (k2 = 8.38/M per min) and L-serine borate (Ki = 34 mM) were poor inhibitors. The activity of the enzyme was not correlated with the logarithmic phase of growth of the parasites and steadily decreases with the age of the cultures. PMID- 2886294 TI - A vocabulary for medical informatics. AB - The terminology in medical informatics is evolving rapidly. The organizers of MEDINFO and SCAMC have used different sets of keywords to index their documents. Recognizing the limitations of this approach, members of those organizations joined with the National Library of Medicine in the creation of a better terminology for medical informatics. A hierarchical structure was placed on the terms to produce a thesaurus typical of the sort often used in the indexing and retrieving of documents. The building of this thesaurus began with an automatic merging of the thesaurus used by the Association of Computing Machinery and the Information Sciences component of the "Medical Subject Headings." This product was pruned by eliminating terms not related to those in the MEDINFO keyword list or not in the medical informatics literature. Further refinement of the thesaurus resulted from extensive discussions among the authors of this paper. The first major application of this terminology has been to the indexing of the articles in "MEDINFO-86 Proceedings." Major components of this medical informatics thesaurus also have been incorporated into the "Medical Subject Headings." This paper describes the process of preparing the thesaurus and presents an evaluation of its coverage of the "MEDINFO-86 Proceedings." PMID- 2886293 TI - Effect of 24-hour starvation on amino acid pool composition and enzyme activities of rat brown adipose tissue. AB - The effect of 24-hr starvation on the amino acid pool composition and its concentration ratios with respect to blood and plasma as well as the activities of alanine, aspartate and branched chain amino acid transaminases, glutamate dehydrogenase, glutamine synthetase and adenylate deaminase have been studied in rat brown adipose tissue. Starvation induced a considerable decrease of pool amino acid concentration. Alanine and taurine were the amino acids in which the decrease was more marked. Small changes were observed in the activities of the enzymes studied, with decreases only in glutamate dehydrogenase and adenylate deaminase. These changes agree with a decrease in amino acid utilization in this tissue induced by starvation. PMID- 2886295 TI - Susceptibility of Bordetella pertussis and Bordetella parapertussis to 24 antibiotics. AB - The susceptibility of Bordetella pertussis (28 strains) and Bordetella parapertussis (6 strains) to 24 antibiotics (penicillin and cephalosporin derivatives, erythromycin, josamycin, cotrimoxazole, imipenem, aztreonam and fosfomycin) was studied by means of the agar dilution method using charcoal horse blood agar. Piperacillin and mezlocillin showed the highest activity (MIC 0.0039 0.00781 micrograms/ml) against B. pertussis while B. parapertussis was most susceptible to piperacillin (0.03125-0.0625 microgram/ml), mezlocillin and latamoxef (0.125-0.25 microgram/ml). PMID- 2886296 TI - Neurobiological aspects of language in children. AB - This article discusses the relevance of the study of the neurobiology of cognitive development, both for an understanding of the neural bases of cognition and of the nature of cognition itself. A key issue is the age at which hemisphere specialization first appears and whether it changes over time. The neuropsychological literature concerning language in both normal and brain damaged children is reviewed. The usefulness of studying cognition in other clinical disorders and variation in normal cognition is indicated. The various methods used in the research are described and the methodological and interpretational difficulties arising from the diversity of groups studied and the methods used are discussed. The model is advanced that hemisphere specialization exists from birth onward and does not undergo further change in either its nature or degree. The apparent increase in the extent of hemisphere specialization during childhood is interpreted as an epiphenomenon of the increasing cognitive and behavioral repertoire of the child. Neural plasticity, assumed to underlie recovery of function, is seen as being coexistent with, but independent of, hemisphere specialization. PMID- 2886298 TI - Fetal and neonatal effects of the beta-adrenoceptor blocking agents. AB - The placental transfer of beta-adrenoceptor blocking agents has been well established in the last years. Randomized and/or controlled studies have given a less pessimistic view of the consequences of these drugs on the fetal and neonatal adaptation. In fact, the beta-blockers are able to produce hypotension, bradycardia, respiratory troubles in the newborn infant, troubles which are generally slight when the neonates are full-term. However, even if in good clinical conditions, this kind of neonate should be carefully monitored for at least the first 2 days of life. PMID- 2886297 TI - Alpha 1-adrenergic receptors in the adult, neonatal, and fetal canine heart. AB - Using the radioligand, iodo-2-[beta-(4-hydroxyphenyl)ethylaminomethyl]tetralone ([125I]-IBE 2254), alpha 1-adrenergic receptors were identified in membranes isolated from fetal, neonatal, and adult canine ventricular myocardium. Binding of the radioligand to alpha 1-adrenergic sites in adult canine heart was rapid, reversible, stereoselective and saturable. Computer analysis of binding data indicated 2 classes of receptors; one with very high affinity and limited capacity (Kd = 13 +/- 9 pM, Bmax = 25 +/- 15 fmol/mg, n = 5) and a second site with lower affinity and greater capacity (Kd = 1.20 +/- 0.43 nM, Bmax = 510 +/- 165 fmol/mg). Two sites were also identified in membranes isolated from fetal and neonatal canine ventricular myocardium. At the higher affinity site, all the age groups displayed similar capacities and affinities. At the lower affinity site, however both fetal and neonatal membranes displayed greater capacity than that of the adult. PMID- 2886299 TI - HLA and T-cell receptor genes in insulin-dependent diabetes mellitus. PMID- 2886300 TI - Hepatic UDP-glucose and UDP-glucuronic acid synthesis rates in rats during a reduced energy state. AB - Hepatic synthesis rates of UDP-glucose and UDP-glucuronic acid were determined in rats. Two high pressure liquid chromatographic methods were developed to quantitate and isolate UTP, UDP-glucose, and UDP-glucuronic acid from perchloric acid extracts of rat liver. The specific activities of UTP, UDP-glucose, and UDP glucuronic acid were determined in liver samples obtained from rats killed by cervical dislocation at various times after [6-14C]orotic acid administration. Synthesis rates were calculated from the rate of change in specific activities of the compound of interest and its immediate precursor and the concentration of the compound of interest. Synthesis rates of UDP-glucose and UDP-glucuronic acid were 102 +/- 9 and 99 +/- 1 nmol X min-1 X g of liver-1, respectively. UDP-glucuronic acid synthesis apparently accounts for most of the UDP-glucose produced during a period (8 a.m.-10 a.m.) when glycogen synthesis is low. The effect of an ethionine-induced reduction of energy state on these basal synthesis rates was examined. UDP-Glucose and UDP-glucuronic acid synthesis rates were decreased by approximately 80%. In summary, the hepatic synthesis rates of UDP-glucose and UDP glucuronic acid are approximately 100 nmol X min-1 X g of liver-1, and a reduced energy state can decrease these synthesis rates in vivo. PMID- 2886301 TI - Metabolism and distribution of 14C- and 35S-labeled carbon disulfide in immature rats of different ages. AB - The metabolism and distribution of 14C- and 35S-CS2 was examined in 1-, 5-, 10-, 20-, 30-, and 40-day-old rats. During a 3-hr period following an ip dose of 14C CS2, 58-83% of the dose was expired as CS2 and 4-9% was metabolized to expired CO2 depending on age. Thirty- and forty-day-old rats metabolized significantly more CS2 to CO2 and expired significantly less CS2 than 1- through 20-day-old rats. At the end of the measured expiration period, only biotransformation products of CS2, which were in part covalently bound, remained in tissues from rats of all ages. Tissue levels of 35S-CS2-derived radioactivity exceeded levels of 14C-CS2-derived radioactivity indicating that sulfur metabolites free from the carbon atom of CS2 were formed in rats as young as 1 day of age. The 35S-CS2 derived radioactivity per g of tissue and thus 35S covalently bound to tissue protein was significantly higher in 1- through 20-day-old rats than in 30- and 40 day-old rats. Twenty-four hr after dosing, up to 13 times more 35S-labeled metabolites were covalently bound in organs from 1-day-old rats than in similar organs from 40-day-old rats. The results showed that elimination of the biotransformation products of CS2, in particular the covalently binding sulfur metabolites, was prolonged in newborn rats in comparison to 40-day-old rats. PMID- 2886302 TI - In vivo and in vitro 1-methylxanthine metabolism in the rat. Evidence that the dehydrogenase form of xanthine oxidase predominates in intact perfused liver. AB - Concentrations of 1-, 3-, and 7-methylxanthine and their uric acid metabolites were measured in plasma and brain affusate 20 min after ip injection of the monomethylxanthines into rats. 3-Methylxanthine was not metabolized to 3 methyluric acid. Similar concentrations of 7-methylxanthine and 7-methyluric acid were detected in both plasma and brain affusate. The oxidation of 1 methylxanthine to 1-methyluric acid occurred so rapidly that the parent compound could not be detected in plasma, and only low concentrations could be detected in brain. Similar patterns in rates of metabolism (1-methyl- greater than 7-methyl- much greater than 3-methylxanthine) were observed in both intact animals and perfused rat liver. The metabolism of 1-methylxanthine to 1-methyluric acid in perfused livers could be explained on the basis of the dehydrogenase form of xanthine oxidase. This conclusion is supported by the observations that the stoichiometry between oxygen utilization and methylurate formation was not consistent with catalysis by the oxidase form of the enzyme and that NADH formed from the metabolism of ethanol strongly inhibited 1-methylxanthine oxidation. In perfused liver, anaerobic conditions decreased rates of 1-methylxanthine metabolism by only 24%. These data demonstrate the presence of oxidizing substrates other than oxygen and NAD+ which are capable of maintaining xanthine oxidase activity during hypoxia. Moreover, rates of 1-methylxanthine metabolism during anoxia could be restored to normal, aerobic values by the infusion of pyruvate, which increased hepatic levels of NAD+. These data demonstrate that changes in the hepatic oxidation-reduction state may dramatically affect rates of xanthine oxidase-dependent metabolism in intact cells. PMID- 2886303 TI - Pharmacokinetic and deuterium isotope effect studies on the metabolism of formaldehyde and formate to carbon dioxide in rats in vivo. AB - The effect of deuterium substitution on the metabolism of formaldehyde and formate to carbon dioxide in vivo was examined. Four groups of male Sprague Dawley rats were injected ip with carbon-14-labeled formaldehyde, formaldehyde d2, sodium formate, or sodium formate-d at doses of 0.67 mmol/kg. Similar rates of labeled carbon dioxide exhalation were observed for the four groups of animals, the cumulative excretion of 14CO2 in breath reaching 68-71% of the theoretical value 12 hr after injection in all cases. Plots of amount remaining to be excreted showed that the metabolism was biexponential, with half-lives of approximately 0.4 and 3 hr for the two phases for each of the four compounds. Competitive experiments in which equimolar mixtures of CH2O with CD2O or HCO2- with DCO2- were injected also failed to reveal a substantial isotope effect, although the cumulative conversion of formate to carbon dioxide was significantly higher than that of its deuterated analog at four time points in the middle of the 8-hr mixed-isotope experiment. The data indicate that deuterium substitution has little or no effect on the rates and extents of in vivo oxidation of these 1 carbon species to carbon dioxide, although a small decrease of up to 10% in reactivity under the conditions employed cannot be excluded. The results support the use of carbon dioxide exhalation data in the measurement of deuterium isotope effects on oxidative demethylation reactions such as those that occur in the activation of the carcinogen, N-nitrosodimethylamine. PMID- 2886304 TI - 3,4-Dichlorobenzyloxyacetic acid is extensively metabolized to a taurine conjugate in rats. AB - The metabolism of the antisickling agent 3,4-dichlorobenzyloxyacetic acid (3,4 DCBAA) was examined after ip administration to rats. Within 5 days after administration of radiolabeled 3,4-DCBAA, 77.4 +/- 4.6% of the dose was recovered in the urine and only 3.2 +/- 0.5% was recovered in the feces. Metabolites in the urine were isolated and characterized by HPLC, electron impact MS, and LC/MS, and their identities were confirmed by comparing their spectra with those of synthetic standards. Quantitation of these urinary metabolites revealed that the majority of the radioactive dose was excreted as a taurine conjugate (60.1 +/- 4.4%), while lesser amounts were excreted as 3,4-dichlorohippurate, unchanged 3,4 DCBAA, the glycine conjugate of 3,4-DCBAA, and a polar unknown which is believed to be glycolic acid. A pathway involving an initial O-dealkylation at the benzyl carbon of 3,4-DCBAA and proceeding through the glycine conjugation of 3,4 dichlorobenzoic acid has been proposed to explain the formation of 3,4 dichlorohippurate and the polar unknown. The extensive conjugation of 3,4-DCBAA with taurine is an unprecedented observation in rats, which usually utilize glycine for amino acid conjugation reactions. Further studies with 3,4-DCBAA may provide insight into the enzymatic mechanisms of taurine conjugation, which are not well defined at this time. PMID- 2886305 TI - Diazepam metabolism in cultured hepatocytes from rat, rabbit, dog, guinea pig, and man. AB - Diazepam metabolism has been investigated in cultured hepatocytes from rat, rabbit, dog, guinea pig, and man. The metabolite profile obtained by HPLC analysis of the culture medium indicated that substantial differences exist corresponding to known species differences in the metabolite profile of diazepam in vivo. These differences were attributed to a combination of the rate at which a metabolite was formed and the rate at which it is removed from the medium by further metabolism. The intrinsic clearance of nordiazepam in hepatocytes from each of the species exhibited the most marked species variation (rat much greater than guinea pig greater than rabbit greater than human greater than dog). Species that exhibited a high intrinsic clearance for nordiazepam were also those species that exhibited significant hydroxylation at the 4'-site of the molecule. The disappearance of diazepam was rapid in rat, dog, and guinea pig hepatocytes, but slow in human hepatocytes. Moreover, rat and human hepatocytes exhibited different saturability of diazepam clearance with respect to diazepam concentration accounting, at least in part, for the different rates of diazepam metabolism in the different species. These results support the value of hepatocytes in drug metabolism studies and especially in studies of species differences in metabolism. PMID- 2886306 TI - Disposition of 8-methoxypsoralen in the rat. Induction of metabolism in vivo and in vitro and identification of urinary metabolites by thermospray mass spectrometry. AB - The pharmacokinetics and metabolism of 8-methoxypsoralen (8-MOP) were measured in the catheterized rat after pretreatment for 3 days with phenobarbital (PB), beta naphthoflavone (BNF), 8-MOP, or vehicle. After an iv injection of 10 mg/kg of [14C]8-MOP, timed blood samples were collected and analyzed using a sensitive and specific assay for [14C]8-MOP. Total body clearance of 8-MOP increased from 0.55 +/- 0.06 liter/kg/hr in control rats to 5.6 +/- 0.4, 2.7 +/- 0.4, and 1.2 +/- 0.0 liters/kg/hr in rats pretreated with BNF, PB, and 8-MOP, respectively, indicating that all three compounds are inducers of 8-MOP metabolism. The pattern of urinary metabolites was altered by the enzyme inducers. The urinary excretion of the sulfate conjugate of 5-hydroxy-8-methoxypsoralen was increased from 10 to 40% of the dose after pretreatment with PB. This intact conjugate was identified using thermospray and fast atom bombardment mass spectrometry. Pretreatment with 8-MOP and BNF increased 2- and 3-fold, respectively, the urinary excretion of a labile sulfate conjugate of 5,8-dihydroxypsoralen. Metabolism of 8-MOP was demonstrated in the 9000 g supernatant and microsomes of rat liver and shown to be inducible by pretreatment of rats with BNF, PB, and 8-MOP. 8-MOP was metabolized in incubations with liver microsomes at rates of 0.22 +/- 0.06, 0.38 +/- 0.06, 0.78 +/- 0.07, and 0.91 +/- 0.03 nmol/min/mg of protein for vehicle, 8-MOP-, PB-, and BNF-pretreated rats, respectively. Results of our investigation indicate that the success of therapy with 8-MOP may be influenced by pharmacokinetic interactions with other drugs. PMID- 2886307 TI - Effects of cisplatin-induced nephrotoxicity on gentamicin pharmacokinetics in rats. AB - The effects of cisplatin-induced nephrotoxicity on the pharmacokinetics of a renally excreted antibiotic, gentamicin, were studied in F-344 rats. A single dose of gentamicin (30 mg/kg, iv) was given to different groups of rats alone, at the same time as, or on day 4, 7, 15, or 29 following cisplatin administration (6 mg/kg, iv). Cisplatin caused a significant decrease in gentamicin clearance and an elevation of gentamicin levels in plasma, kidneys, liver, and spleen at all the time points that were tested except concomitant administration. The maximum effect was seen when gentamicin was given on day 7 following cisplatin. The total clearance of gentamicin was reduced from 11 +/- 5 ml/(min X kg) in control rats to 2 +/- 2 ml/(min X kg) in cisplatin-treated rats. Twenty-four-hr urinary gentamicin excretion was decreased to 34 +/- 13% of the dose (control rats excreted 93 +/- 4% of dose). Rats given only gentamicin had a creatinine clearance of 5.9 +/- 0.6 ml/(min X kg), whereas those given gentamicin on day 7 following cisplatin had a creatinine clearance of 0.4 +/- 0.2 ml/(min X kg). Thus, cisplatin reduced gentamicin excretion in rats, resulting in elevated antibiotic levels in plasma and tissues for at least a month. Prior exposure to cisplatin may therefore be associated with an increased risk of toxicity from gentamicin, even when the antibiotic is administered in therapeutic doses. The effects of cisplatin on other renally excreted drugs need to be evaluated. PMID- 2886308 TI - Induction and inhibition of rat hepatic drug metabolism by N-substituted imidazole drugs. AB - Three daily administrations of N-substituted imidazole antimycotics, clotrimazole (CloTZ, 75 mg/kg/day), miconazole (MCZ, 150 mg/kg/day), or tioconazole (TCZ, 150 mg/kg/day), but not the 4,5-disubstituted imidazole cimetidine (350 mg/kg/day) or imidazole (200 mg/kg/day for 4 days), induced rat hepatic cytochrome P-450 and other drug-metabolizing enzymes. These findings paralleled in vitro observations where CloTZ, MCZ, and TCZ were several orders of magnitude more potent as inhibitors of p-nitroanisole O-demethylase activity in control male rat liver microsomes than cimetidine or imidazole. Although no marked difference in inhibitory potency was evident among the N-substituted imidazoles, there were qualitative and quantitative differences in the profiles and extents of induction of various cytochrome P-450-dependent monooxygenases and Phase II conjugation enzymes. Cytochrome P-450 was elevated dramatically by CloTZ (3-4 times the control) and to a lesser extent by MCZ and TCZ (congruent to 1.5 times the control). For all agents, there was an increase in metyrapone binding approximately equivalent to the additional (i.e. above control) cytochrome P-450. Despite the large difference in cytochrome P-450 induction by CloTZ, MCZ, and TCZ, these agents elevated p-nitroanisole demethylase and aniline hydroxylase to similar extents (3-5 X and 1-2 X control, respectively). All agents induced erythromycin and ethylmorphine demethylation in proportion to cytochrome P-450. Ethoxyresorufin O-de-ethylation was not substantially affected by any agent. Large differences in the extent and specificity of induction of microsomal glucuronide conjugations were also evident.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886309 TI - Influence of cytochrome b5 on the stoichiometry of the different oxidative reactions catalyzed by liver microsomal cytochrome P-450. AB - Stoichiometries of oxygen and NADPH consumption and product and hydrogen peroxide formation are examined for three forms of cytochrome P-450, LM2, RLM2, and RLM5, using several different substrates. As reported earlier, during the metabolism of some substrates [Gorsky, Koop, and Coon: J. Biol. Chem. 259, 6812-6817 (1984)], excess NADPH and oxygen are consumed suggesting that a 4-electron reduction of oxygen to water occurs. Similar effects are seen with testosterone as substrate for the constitutive forms of P-450, RLM2 and RLM5. However, when aminopyrine or p-nitroanisole serve as substrate, none of the forms of P-450 consumed excess NADPH or oxygen. Thus, consumption of excess NADPH and oxygen appears to be the result of the substrate used. Cytochrome b5 stimulates turnover of LM2 and RLM5 but not RLM2. With LM2, it causes a metabolic switching to occur between the monooxygenase and the NADPH-oxidase reaction. Although RLM5 is also stimulated by cytochrome b5, no metabolic switching occurs. Cytochrome b5 did not affect the proportion of excess NADPH or oxygen consumed. PMID- 2886310 TI - The formation of glutathione conjugate derived from propranolol. AB - Mixed function oxidases in liver microsomes from 3-methylcholanthrene-pretreated guinea pigs converted S-propranolol to 4-hydroxypropranolol, 5 hydroxypropranolol, and desisopropyl-propranolol. The addition of glutathione and cytosol from rat liver to the system resulted in the formation of a water-soluble metabolite. Evidence that the metabolite was a glutathione adduct was obtained by showing that treatment with gamma-glutamyltranspeptidase changed its HPLC retention time. The formation of the glutathione adduct required glutathione S transferases in cytosol and was accompanied by a decrease in the formation of 5 hydroxypropranolol, but not of 4-hydroxypropranolol or desisopropylpropranolol. The formation of the propranolol-glutathione adduct was confirmed by two independent approaches. When [14C]glutathione and [3H]S-propranolol were used, the relationship between 14C and 3H in the metabolite indicated that it contained equal amounts of glutathione and propranolol. When a pseudoracemic mixture of S propranolol and [2,4-2H2]R-propranolol was used, thermospray LC/MS analysis of the glutathione adduct revealed two peaks having different retention times. The first peak, representing a [2,4-2H2]R-propranolol-GSH adduct, gave fragment ions at m/z 294, 278, 262, while the second, which represented the S-propranolol-GSH adduct, gave fragment ions having 2 mass units less than those obtained with [2,4 2H2]R-propranolol. There was no evidence of any loss of deuterium during the formation of these fragment ions. The material in both peaks gave ions of m/z 308, 147, and 130, which is consistent with the presence of a glutathione group. PMID- 2886311 TI - The oxidation of acrolein by rat liver aldehyde dehydrogenases. Relation to allyl alcohol hepatotoxicity. AB - The oxidation of acrolein by aldehyde dehydrogenase was studied in several subcellular fractions of rat liver by measuring acrolein-dependent production of NADH from NAD+. Mitochondrial and cytosolic fractions each contained two aldehyde dehydrogenase activities with Km values for acrolein of 0.4-0.7 mM and 0.015 0.025 mM. Microsomes demonstrated only a high Km (1.5 mM) activity. The low Km activities of mitochondria and cytosol differed in their sensitivity to inhibition by chloral hydrate and in their response to 1 mM MgCl2 (activation vs. inhibition). The metabolism of acrolein by low Km aldehyde dehydrogenase activities was markedly depressed in mitochondrial or cytosolic fractions from rats pretreated with cyanamide (2 mg/kg for 1 hr) or disulfiram (100 mg/kg for 24 hr). The effect of aldehyde dehydrogenase inhibition on allyl alcohol toxicity was determined by pretreating rats with cyanamide or disulfiram prior to treatment with allyl alcohol. Hepatotoxicity was assessed on the basis of elevated serum alanine aminotransferase and sorbitol dehydrogenase activities and the loss of microsomal cytochrome P-450. Pretreatment with the aldehyde dehydrogenase inhibitors enhanced the hepatotoxicity of allyl alcohol in both male and female rats. The results suggest that acrolein metabolism by rat liver aldehyde dehydrogenase isozymes is important for the inactivation of allyl alcohol-derived acrolein. PMID- 2886312 TI - The disposition and elimination of two sequential doses of 2,4,5,2',4',5' hexachlorobiphenyl. AB - It has been suggested based on fecal elimination data that a second dose of 2,4,5,2',4',5'-hexachlorobiphenyl (6-CB) is eliminated more rapidly from male rats than a first dose of 6-CB due to a differential accumulation of the two 6-CB doses within individual adipocytes. This phenomenon was further examined and extended to assess tissue levels of the compound in male rats which received either 0.6 mg/kg unlabeled or 14C-6-CB iv (dose 1). Fourteen days later, those animals which had received unlabeled 6-CB were administered 0.6 mg/kg 14C-6-CB. One-half of those rats which had received 14C-6-CB as dose 1 were administered unlabeled 6-CB after 14 days, and the remainder did not receive a second dose. The fecal excretion of radiolabeled 6-CB from rats treated only with 14C-6-CB was 5.3% of the total dose from days 14 through 28 post-treatment. Those rats receiving 14C-6-CB followed by unlabeled 6-CB excreted 4.4% of the total radiolabeled dose. Animals treated with 14C-6-CB as the second dose excreted 9% of their total radiolabeled dose within 14 days of treatment and those receiving only 14C-6-CB excreted 11% over the same time interval. Urinary elimination of radioactivity was negligible in all treatment groups. The pattern of distribution of 14C-6-CB in tissues was similar among all treatment groups. These data suggest that a second dose of 6-CB is not distributed differently from the first in growing male rats. PMID- 2886313 TI - Absorption, distribution, metabolism, and excretion of 1,2-dihydro-2,2,4 trimethylquinoline in the male F344 rat. AB - 1,2-Dihydro-2,2,4-trimethylquinoline (TMQ), an antioxidant used in the rubber industry, was readily absorbed from the gastrointestinal tract of the male Fischer 344/N rat and rapidly distributed throughout the body tissues. Absorption, distribution, metabolism, and excretion were not significantly affected by dose in the range 11.5-1150 mumol/kg. Following iv administration, the greatest amounts of TMQ-derived radioactivity were present in the high volume tissues including muscle, adipose, skin, liver, and blood. TMQ had no particular affinity for any tissue. TMQ-derived radioactivity was excreted primarily in urine (60-70%) and feces (20-30%) within 3 days after administration. Greater than 99% of the TMQ dose excreted in urine and feces was in the form of metabolites. Urine contained two major and ten minor metabolites while feces contained two major and four minor metabolites. The two major TMQ metabolites in urine were identified by NMR and mass spectroscopy as the O-sulfate conjugate of 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline and the monosulfate conjugate of 1,2-dihydro-1,6-dihydroxy-2,2,4-trimethylquinoline. In vitro studies with liver subcellular fractions suggest that most of the metabolites present in urine, feces, and bile are the products of mixed function oxidase activity and conjugates of these metabolites. Multiple exposure of rats to high TMQ doses (1150 mumol/kg) resulted in some bioaccumulation of TMQ-derived radioactivity in all tissues examined, but these residues did not persist when dosing was discontinued. PMID- 2886314 TI - Pharmacokinetics of griseofulvin in blood and skin suction blister fluid of rats. AB - The penetration of griseofulvin to its site of action was investigated in the rat using subepidermal blisters induced by suction as a model. Griseofulvin was administered iv at a dose of 20 mg/kg after which blood, suction blister fluid (SBF), and skin tissue were sampled over a 300-min time period. The blood level/time course can be described by a two-compartment model. During the terminal phase, concentrations of drug in blood, SBF, and cutis declined in parallel, with respective half-lives of 71.0, 70.4, and 74.6 min. In SBF, maximum concentrations (2.35 +/- 0.36 micrograms/ml) were obtained 60 min postinjection, drug levels increased until the concentrations of unbound griseofulvin in SBF and plasma were identical. Time to peak concentration in cutis was shorter (20 min; 13.9 +/- 0.5 micrograms/ml). As the dermatophytes are located in the horny layer, the determination of griseofulvin in SBF seems to be a more suitable assay for determining the griseofulvin level profile at its site of action. In addition, the level of unbound, and thus active, griseofulvin in SBF was severalfold lower than the concentration of total drug in excised skin tissue. Up to now, the latter value has been considered to indicate that the concentration of griseofulvin in the skin is comparable to the in vitro sensitivity of dermatophytes. The present results show that this seems to be no longer justified. PMID- 2886315 TI - Tissue distribution, disposition, and metabolism of cyclosporine in rats. AB - Tissue distribution, disposition, and metabolism of 3H-cyclosporine were studied in rats after single and repeated oral doses of 10 and 30 mg/kg and after an iv dose of 3 mg/kg. The oral doses of 10 and 30 mg/kg were dissolved in polyethylene glycol 200/ethanol or in olive oil/Labrafil/ethanol. Absorption from both formulations was slow and incomplete, with peak 3H blood levels at 3-4 hr. Approximately 30% of the radioactive dose was absorbed, which is consistent with oral bioavailability data for cyclosporine. More than 70% of the radioactivity was excreted in feces and up to 15% in urine. Elimination via the bile accounted for 10 and 60% of the oral and iv doses, respectively. Since unchanged cyclosporine predominated in both blood and tissues at early time points, the half-lives of the distribution phases (t 1/2 alpha) of parent drug and of total radioactivity were similar. In blood, kidney, liver, and lymph nodes, t 1/2 alpha of cyclosporine ranged from 6-10 hr. Elimination of radioactivity from the systemic circulation was multiphasic, with a terminal half-life of 20-30 hr. 3H Cyclosporine was extensively distributed throughout the body, with highest concentrations in liver, kidney, endocrine glands, and adipose tissue. The concentrations of both total radioactivity and parent drug were greater in tissues than in blood, which is consistent with the high lipid solubility of cyclosporine and some of its metabolites. Skin and adipose tissue were the main storage sites for unchanged cyclosporine. Elimination half-lives were slower for most tissues than for blood and increased with multiple dosing. The amount of unchanged drug was negligible in urine and bile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886316 TI - Metabolism of cyclosporin A. I. Study in freshly isolated rabbit hepatocytes. AB - The metabolism of cyclosporin A (CsA), a widely used immunosuppressive agent, was evaluated in freshly isolated rabbit hepatocytes by HPLC which separated CsA from its major group of derivatives, e.g. "first generation" metabolites (monohydroxylated and N-demethylated) and "second generation" derivatives (dihydroxylated and dihydroxy-N-demethylated). After exposure of hepatocytes to radiolabeled CsA (0.5 mg/liter), CsA was rapidly accumulated inside the cells and metabolized. The dihydroxylated metabolites represent the major intracellular forms after 1 hr. CsA metabolites synthesized inside the cells are then rapidly detected in the extracellular compartment. Unchanged drug and the various metabolites are concentrated inside the cells with transmembrane chemical gradients ranging between 20:1 and 40:1. Transport and metabolic processes for CsA have been evaluated over the following CsA extracellular concentration range, 0.1-10 mg/liter. Metabolism appears to be the rate-limiting step. The apparent affinity constant of CsA for the enzyme system involved in its metabolism is approximately 15 microM. Besides the lipophilicity of the molecule, which is responsible for the retention of CsA and its metabolites in the intracellular compartment, the presence of a binding component(s) in the hepatocytes was also demonstrated. CsA and its metabolites seem to have similar affinities for this binding site. These studies demonstrate that CsA is rapidly transformed inside the hepatocytes to various metabolites which may play an important role in the pharmacological activity of the drug and/or in its clinical toxicity. PMID- 2886317 TI - Metabolism of cyclosporin A. II. Implication of the macrolide antibiotic inducible cytochrome P-450 3c from rabbit liver microsomes. AB - The in vitro metabolism of cyclosporin A (CsA) was investigated by rabbit liver microsomes in order to identify the form(s) of cytochrome P-450 responsible for its biotransformation. Metabolites including monohydroxy-, N-demethylated, dihydroxy- and dihydroxy-N-demethylated derivatives were detected and quantified by HPLC from incubates of liver microsomes, CsA, and NADPH. Kinetic data indicated that monohydroxy- and N-demethylated derivatives were first generated and then served as substrates for production of dihydroxylated derivatives. Liver microsomes from phenobarbital-, beta-naphthoflavone-, triacetyloleandomycin-, erythromycin-, or rifampicin-treated and untreated rabbits were investigated, but only microsomes from animals treated with macrolide antibiotics (specific inducers of form P-450 3c) exhibited a type I binding spectrum upon CsA addition (Ks = 1.5 +/- 0.5 microM) and extensively metabolized the drug to all groups of derivatives (Km = 5.0 +/- 0.5 microM, Vmax = 1.0 +/- 0.2 nmol/mg/min). A linear correlation existed between CsA oxidase activity and P-450 3c specific content. Antibodies to P-450 3c strongly inhibited CsA oxidase activity of microsomes from macrolide antibiotic-induced animals, whereas antibodies to other forms, including P-450 2, 3b, 4, and 6, did not. When highly purified forms of P-450, including P-450 2, 3b, 3c, and 4, were assayed in a reconstituted system, only P 450 3c exhibited type I binding spectrum upon CsA addition (Ks = 1.4 +/- 0.5 microM) and extensively metabolized the drug to all derivatives. We conclude that the macrolide antibiotic-inducible form P-450 3c (or P-450 3c related from(s)) is responsible for the major part of CsA metabolism by rabbit liver microsomes. PMID- 2886318 TI - Urinary metabolites of busulfan in the rat. AB - After ip administration of 15 mg/kg [1,4-14C]busulfan to rat, the urinary excretion was 70% of the total radioactivity after 72 hr. Three major metabolites were isolated and quantified by HPLC. Of the total radioactivity in the urine, unchanged busulfan was excreted as a minor amount (6%) and the following metabolites were identified as: 3-hydroxysulfolane (39%), tetrahydrothiophene 1 oxide (20%), and sulfolane (13%) using GC/MS and NMR spectroscopy. The cytotoxicity of busulfan and its major metabolites was examined using a V79 Chinese hamster cell line. PMID- 2886319 TI - Liver metabolism of budesonide in rat, mouse, and man. Comparative aspects. AB - The metabolism of budesonide, (22RS)-16 alpha, 17 alpha-butylidenedioxy-11 beta,21-dihydroxypregna-1,4-diene- 3,20-dione, was studied in the 9000g supernatant fraction of livers from rat, mouse, and man. The two budesonide C-22 epimers produced different metabolites. This was explained by substrate-selective oxidation of the nonsymmetric 16 alpha, 17 alpha-acetal substituent. Epimer 22R gave 16 alpha-hydroxyprednisolone, while epimer 22S produced a metabolite tentatively identified as 23-hydroxybudesonide. Otherwise, budesonide followed the general metabolic pathways reported for synthetic glucocorticoids. Thus, oxidative metabolism predominated, 6 beta-hydroxybudesonide and delta 6 budesonide being identified in all investigated species. Reductive metabolism, giving 4,5 beta-dihydrobudesonide and 3,4,5 beta-tetrahydrobudesonide, was most pronounced in the rat. Rates and routes of budesonide metabolism were most similar in mouse and human livers. This implies that the mouse is a more relevant species than the rat in studies of the pharmacology and toxicology of budesonide. PMID- 2886320 TI - Metabolic acetal splitting of budesonide. A novel inactivation pathway for topical glucocorticoids. AB - Topical glucocorticoids usually have a high intrinsic glucocorticoid potency and may, after systemic uptake, induce side effects. The systemic inactivation of budesonide is rapid due to extensive liver biotransformation. The major metabolic pathway, 16 alpha, 17 alpha-acetal splitting, is unique for budesonide within this group of compounds. This biotransformation is catalyzed by microsomal monooxygenases and proceeds via hydroxylation and subsequent rearrangement to an intermediary ester. The ester is cleaved by hydrolysis to 16 alpha hydroxyprednisolone and butyric acid. The hydrolysis product 16 alpha hydroxyprednisolone has strongly reduced glucocorticoid activity. PMID- 2886321 TI - Glutathione conjugation of 1,2-dibromo-1-phenylethane in rats in vivo. AB - The metabolism of 1,2-dibromo-1-phenylethane (DBPE) was studied in rats. Administration of DBPE orally, in doses of 0.25-1.25 mmol/kg (66-330 mg/kg), to male Wistar rats resulted in the excretion of a single mercapturic acid in urine. The methyl esters of three potential mercapturic acid metabolites were synthesized: N-acetyl-S-(2-oxo-2-phenylethyl)-L-cysteine methyl ester (O),N acetyl-S-(2-hydroxy-1-phenylethyl)-L-cysteine methyl ester (I), and N-acetyl-S-(2 hydroxy-2-phenylethyl)-L-cysteine methyl ester (II). GC/MS analysis showed that the methyl ester of the excreted mercapturic acid was identical with II. Quantitative measurement of II in urine by GLC showed that, after 24 hr, excretion of the mercapturic acid was almost complete and amounted to 41% of the administered dose. At doses higher than 1.00 mmol/kg, the excretion no longer increased. Inhibition of the oxidative pathways by ip injection of 1 phenylimidazole resulted in an excretion decrease of about 40%. (Pre)treatment with diethyl maleate lowered the excretion of mercapturic acid by 30-60%. Glutathione conjugates synthesized from DBPE and styrene oxide were separated by HPLC. Both compounds can produce the same two pairs of diastereomers, viz. (R)- and (S)-(2-hydroxy-1-phenyl-ethyl)glutathione ((R)-1 and (S)-1), and (R)- and (S) (2-hydroxy-2-phenylethyl)glutathione ((R)-2 and (S)-2). These could be separated in the order (R)-2, (R)-1, (S)-1, and (S)-2 within 20 min. This method was also applied to examine glutathione conjugates excreted in bile after DBPE administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886322 TI - N-hydroxymethyl metabolites of 450191-S, a 1H-1,2,4,-triazolyl benzophenone derivative, in dog plasma. AB - In a metabolic experiment of 5-[(2-aminoacetamido)methyl]-1-[4-chloro-2-(o chlorobenzoyl)phenyl ]-N, N-dimethyl-1H-1,2,4,-triazole-3-carboxamide hydrochloride dihydrate (450191-S) in dogs, two new metabolites 8-chloro-6-(o chlorophenyl)-N-hydroxymethyl-4H-1,2,4-triazolo [1,5-a] [1,4]benzodiazepine-2 carboxamide (M-A) and 8-chloro-6-(o-chlorophenyl)-N-hydroxymethyl-N-methyl-4H 1,2,4-triazolo [1,5-a] [1,4]benzodiazepine-2-carboxamide (M-D) in plasma were found in addition to 8-chloro-6-(o-chlorophenyl)-N,N-dimethyl-4H-1,2,4 triazolo[1,5-a] [1,4] benzodiazepine-2-carboxamide (M-1), 8-chloro-6-(o chlorophenyl)-N-methyl-4H-1,2,4-triazolo[1,5-a] [1,4] benzodiazepine-2 carboxamide (M-2), 8-chloro-6-(o-chlorophenyl)-4H-1,2,4-triazolo-[1,5-a] [1,4] benzodiazepine-2-carboxamide (M-3), and 8-chloro-6-(o-chlorophenyl)-4H-1,2,4 triazolo[1,5-a] [1,4] benzodiazepine-2-carboxylic acid (M-4). The structures of N hydroxymethyl metabolites were elucidated mainly by mass spectrometry. The structures were confirmed by synthesizing the authentic compounds and comparing the mass spectra. PMID- 2886323 TI - Plasma concentration profiles of human recombinant interleukin-2 (HrIL-2) in the rat following administration by various systemic routes. PMID- 2886324 TI - Dose- and time-dependent effect of levamisole on the elimination of antipyrine in the rat. PMID- 2886326 TI - Salazopyrin EN-tabs: an enteric-coated case that is hard to take. PMID- 2886325 TI - Drug-antacid interactions: assessment of clinical importance. AB - Antacids and adsorbents are commonly used preparations that are generally considered to be pharmacologically inert and free from adverse effects. They may, however, interact with a diverse range of primary drugs and the sequelae can be disadvantageous to the efficacy of the primary medication. Many such reports in the literature are based on animal experiments, or on single-dose studies in healthy subjects. Some reports are anecdotal and are unconfirmed; others are based solely on in vitro evidence. Potentially important interactions have been suggested for a relatively small group of drugs: tetracyclines, phenytoin, digoxin, chloroquine, cimetidine, quinidine, nonsteroidal antiinflammatory drugs, and beta-blocking agents. The evidence for these has been critically evaluated, as well as for antacid-anticoagulant and antacid-nitrofurantoin interactions that have been wrongly emphasized in the literature. The majority of literature reports on interactions with antacids have been overemphasized; only ferrous sulfate-, isoniazid-, and tetracycline-antacid interactions fall into a category I importance (scale I-III of descending importance). This category is for those interactions with good evidence of actual or potential importance in patients or in relevant studies on normal subjects. PMID- 2886328 TI - [Periodic hypokalemic paralysis caused by high endogenous catecholamine activity?]. PMID- 2886327 TI - [Severe periodic hypokalemic paralysis. Prevention using beta-receptor blockade]. AB - For ten years, severe physical exercise in a 24 year old male patient had been an almost constant trigger of frequent attacks of pareses which were mostly accompanied by complete tetraplegia and once by the occurrence of cardiac arrest with atrial fibrillation. During the attack, the serum potassium concentration fell to 1.2 mmol/l, whereas the intraleukocytic potassium concentration rose from 136 mmol/l to 149 mmol/l. The catecholamine excretion in the urine was raised during the first 24 hours after admission as an emergency (189 micrograms noradrenalin and 54 micrograms adrenalin). After intravenous adrenalin infusion (0.01-0.1 microgram/kg X min) during the symptom-free interval, there was a major fall of the serum potassium concentration from 3.9 mmol/l to 3.1 mmol/l. This was not accompanied by a raised insulin excretion and could be prevented by prior administration of the nonselective beta blocker propranolol. On the basis of these results, the patient was treated prophylactically with three times 40 mg/d p.o. propranolol. Pareses requiring treatment no longer occurred under this therapy. PMID- 2886329 TI - [Laser-induced shockwave lithotripsy]. PMID- 2886330 TI - [Conversion enzyme inhibitors in the antihypertensive treatment of patients with renal insufficiency]. AB - Changes in serum creatinine concentration and proteinuria over a period of 12 months were analysed retrospectively in hypertensives in renal failure, 39 treated with conversion-enzyme inhibitors and 41 treated with other antihypertensives. The occasionally recorded blood pressures were comparable in the two groups. Median serum creatinine levels in the patients treated with conversion-enzyme inhibitors rose from 2.33 mg/100 ml (range 1.5-5.5) after one month acutely by 0.4 mg/100 ml and then remained essentially constant. In nine patients the level was higher by greater than or equal to 0.5 mg/100 ml after 12 months than at the beginning of treatment. Proteinuria did not show any identifiable changes. On the other hand, in those patients treated with other antihypertensives, median serum creatinine concentration rose gradually over 12 months from 2.4 mg/100 ml (range 1.5-6.0) to 3.45 mg/100 ml (1.5-12.9). In 18 patients the serum creatinine level rose by less than or equal to 0.5 mg/100 ml. Five patients developed side effects to conversion-enzyme inhibitors, but none required discontinuation of treatment. It is concluded that the use of conversion enzyme inhibitors in patients with renal failure is effective and largely safe. It apparently causes less of a rise in serum creatinine than other antihypertensives. PMID- 2886332 TI - [Human acute lymphoblastic leukemia associated with HTLV-I virus and its infection in healthy populations from various regions of the USSR]. AB - Patients with various forms of hemoblastoses (328) and clinically healthy persons (530) were examined for antibodies to HTLV-I. The presence of antibodies was detected in 3 out of 40 patients with acute lymphoblastic leukemia and only in 1 of 70 patients with lymphosarcoma. These data indicate that sporadic cases of T cell leukemia associated with HTLV-I were detected in the USSR. Out of 530 healthy persons only 4 contained antibodies to HTLV-I antigens. PMID- 2886331 TI - [Beta-receptor blockaders in the prevention of hemorrhaging of esophageal varices?]. PMID- 2886333 TI - Molecular size distribution of immunoreactive trypsin and renal tubular dysfunction: role in trypsin plasma-urine transfer. AB - In order to investigate the role of circulating free trypsinogen and renal tubular dysfunction in affecting trypsin plasma-urine transfer, serum immunoreactive trypsin (IRT), its urinary output, IRT molecular size distribution, filtrable immunoreactive trypsin, gamma-glutamyltransferase and alpha-glucosidase outputs were studied in 6 control subjects, 9 patients with pancreatic cancer and 15 with chronic pancreatitis. The majority of immunoreactivity was always eluted at a molecular weight of about 24,000 and might therefore be considered as free trypsinogen. Variable amounts of IRT at higher molecular weights, possibly represented by trypsin-inhibitor complexes, were also detected. Increasing IRT levels were generally accounted for by free trypsinogen, regardless of the nature of the disease. Unlike serum free trypsinogen levels, renal tubular damage, evaluated by means of the excretion of two high-molecular weight urinary enzymes, seems to play a prominent role in explaining trypsin plasma-urine transfer. PMID- 2886335 TI - The role of lysine-132 and arginine-136 in the receptor-binding domain of the K99 fibrillar subunit. AB - The gene encoding the K99 fibrillar adhesin of Escherichia coli has been modified by oligonucleotide-directed, site-specific, mutagenesis. The tryptophan-67, lysine-132, lysine-133 or arginine-136 were replaced by leucine, threonine, threonine and serine, respectively. The threonine-133 mutant fibrillae were indistinguishable from wild-type fibrillae. In contrast, replacement of lysine 132 or arginine-136 by threonine or serine, respectively, resulted in mutant fibrillae which had completely lost adhesive capacity, suggesting that the positive charges of these residues are essential for the interaction with the negatively charged sialic acid residue of the receptor molecules. After the replacement of tryptophan-67 with leucine neither fibrillae nor subunits were detectable, indicating that the mutant product is unstable and that tryptophan-67 has an essential structural role in the K99 subunit. PMID- 2886334 TI - Tissue-specific N-glycosylation, site-specific oligosaccharide patterns and lentil lectin recognition of rat Thy-1. AB - To examine the extent to which protein structure and tissue-type influence glycosylation, we have determined the oligosaccharide structures at each of the three glycosylation sites (Asn-23, 74 and 98) of the cell surface glycoprotein Thy-1 isolated from rat brain and thymus. The results show that there is tissue specificity of glycosylation and that superimposed on this is a significant degree of site-specificity. On the basis of the site distribution of oligosaccharides, we find that no Thy-1 molecules are in common between the two tissues despite the amino acid sequences being identical. We suggest, therefore, that by controlling N-glycosylation a tissue creates an unique set of glycoforms (same polypeptide but with oligosaccharides that differ either in sequence or disposition). The structures at each of the three sites were also determined for the thymocyte Thy-1 that binds to lentil lectin (Thy-1 L+) and for that which does not (Thy-1 L-). Segregation of intact thymus Thy-1 into two distinct sets of glycoforms by lentil lectin was found to be due to the structures at site 74. Analysis of oligosaccharide structures at the 'passenger' sites (23 and 98) suggests that either Thy-1 L+ and Thy-1 L- molecules are made in different cell types or that the biosynthesis of oligosaccharides at one site is influenced by the glycosylation at other sites. PMID- 2886336 TI - The heme biosynthetic pathway in the regenerating rat liver. The relation between enzymes of heme synthesis and growth. AB - Enzymes of heme synthesis, porphyrins and heme content of regenerating rat livers were examined. During the first three days of regeneration the weights of livers of one-third and two-third hepatectomized rats increased 1.5-fold and 2.7-fold and the activity of porphobilinogen deaminase increased 2-fold and 4-fold and was inversely correlated with ferrochelatase activity. delta-Aminolevulinic acid synthase and delta-aminolevulinic acid dehydratase activities were reduced. Concomitantly an increase in the concentration of porphyrins and a decrease in that of heme were observed. The changes in the biosynthetic pathway of heme during rapid growth of the liver are discussed. PMID- 2886338 TI - Temelastine, a novel histamine H1-receptor antagonist, does not induce oxidative hepatic enzyme activity in man. AB - Temelastine (SK&F 93944) is a novel histamine H1-receptor antagonist with a high degree of protein binding and predominant hepatic elimination. The pharmacokinetics of antipyrine were assessed in eight male normal subjects after single oral doses of 10 mg/kg antipyrine, administered prior to chronic dosing with temelastine 100 mg twice daily for 2 weeks, and 48 hours after the last dose of temelastine. After the first dose of antipyrine the mean maximum plasma concentration (Cmax) was 78.3 mumol/l (range: 60.3 to 95.8), the mean AUC (0 infinity) was 1330 mumol.h/l (range: 1030 to 2074), the mean apparent terminal disposition rate constant K was 0.0656 h-1 (range: 0.0428 to 0.0769) and the mean residence time (MRT) was 16.7 h on average (range: 14.4 to 24.1). After the second dose the mean Cmax, AUC (0-infinity) and MRT had slightly increased by on average 11, 5 and 7% respectively whereas the mean K had decreased by 9%. None of the differences between the means of the log-transformed parameters for second first dose reached statistical significance. Temelastine therefore did not appear to induce hepatic oxidative enzyme activity in man, as judged by antipyrine as a model substance. PMID- 2886337 TI - The clinical relevance of alcohol in the Blood Pressure Clinic. AB - There is a limited number of studies conducted in hypertensive patients which support the hypothesis that high alcohol intake is an important reversible cause of raised blood pressure. The validity and effectiveness of alcohol restriction as a treatment of hypertension is difficult to study as there is no suitable placebo substance that can be employed on a clinical trial basis. However, such clinical data that there are, taken with the confirmatory epidemiological work, strongly suggest that hypertensive patients should be questioned and investigated for evidence of high alcohol intake and advised accordingly. PMID- 2886339 TI - Splenic-gonadal fusion in cryptorchidism. PMID- 2886340 TI - Magnesium depletion in patients on long-term chlorthalidone therapy for essential hypertension. AB - Sixty patients were treated for 1 year for essential uncomplicated hypertension, 30 with beta-blockers alone (BB) and 30 with BB and chlorthalidone (CTD). BB did not affect serum K+ or Mg++. In the BB-group there was a statistically significant trend towards retention of Mg++ in a loading test, but the effect was clinically marginal. BB + CTD reduced serum K+ and Mg++ and caused significant Mg++ depletion, as shown by the Mg++ loading test. All the effects were highly significant and were clinically important. The metabolic perturbations due to CTD are potentially dangerous and make this drug unattractive as 'first choice' treatment for hypertension. PMID- 2886341 TI - Airway response to salbutamol and to ipratropium bromide after non-selective and cardioselective beta-blocker. AB - Eight healthy men were randomly assigned in a latin square order to receive single doses of placebo, tertatolol 5 mg, propranolol 80 mg and atenolol 100 mg at 7-day intervals. Resting heart rate and pulmonary function were measured 10 min before and over the 240 min following dosing, and then 15 min after inhalation of salbutamol 200 micrograms and ipratropium bromide 40 micrograms. The three beta-blockers caused similar reductions in resting heart rate throughout the study, whereas placebo had no effect. The three beta-blockers, like placebo, produced no significant change in pulmonary function during the 240 min after dosing. The bronchodilator response to salbutamol after atenolol and placebo was preserved, whereas it was reduced after administration of either of the non-selective beta-blockers, tertatolol and propranolol. An unequivocal response of the airways to ipratropium bromide was observed after tertatolol and propranolol, which was much greater than after atenolol. No response was observed after placebo. Thus, despite bronchial beta 2-blockade, by non-selective beta blockers, bronchodilatation was definitely produced by ipratropium bromide, confirming the predominant role of the parasympathetic system in the autonomic innervation of normal human airways. PMID- 2886342 TI - Actual versus reported benzodiazepine usage by medical outpatients. AB - Benzodiazepines are widely prescribed, and in 1979 almost 10% of the adult population was taking them. Prior studies of outpatient usage of benzodiazepines have relied on survey or prescription data, which may be confounded by noncompliance. To determine the actual use of benzodiazepines, plasma benzodiazepine concentrations were measured in 225 consecutive outpatients from a university cardiology outpatient service. Self reports indicated that the great majority of the patients (191) were taking at least one medicine, and 70 reported being on a psychotropic drug. Seventy-seven patients reported taking benzodiazepines, the majority being on bromazepam (20), diazepam (26) or oxazepam (19). In 25 of those 77 patients, the reported drug could not be detected in plasma. Conversely, in 10 of the 225 patients, benzodiazepines which were not reported were detected (diazepam or flurazepam). Of those taking benzodiazepines, many had a low concentration, suggesting intermittent rather than regular use. Thus, many patients for whom benzodiazepines are prescribed take them irregularly, and a small group uses them without reporting their prescription. These findings have implications for the clinical presentation of illness and for the possibility of drug interactions. PMID- 2886343 TI - Studies on the central effects of the H1-antagonist, loratadine. AB - Effects of loratadine (10, 20 and 40 mg) on visuo-motor coordination, dynamic visual acuity, short-term memory, digit symbol substitution, and on subjective assessments of mood were tested before, and 0.5, 1.5, 3.5 and 5.5 h after ingestion by 6 healthy female adults. There were no effects of 10 or 20 mg loratadine. With 40 mg loratadine the number of substitutions on the digit symbol test was reduced 5.5 h after ingestion, and on dynamic visual acuity response time was increased at 3.5 h and the number of responses missed was increased at 5.5 h. Triprolidine (10 mg) which was used as active control impaired performance on all the tasks and impaired performance was observed at all times after ingestion. Loratadine is a promising antihistamine for individuals involved in skilled activity. The anticipated single daily dose of 10 mg is unlikely to impair performance. PMID- 2886344 TI - The immune response of the mouse to lymphocytic choriomeningitis virus. V. High numbers of cytolytic T lymphocytes are generated in the spleen during acute infection. AB - In the spleens of C57BL/6J (B6) and CBA/J (CBA) mice undergoing acute infection with lymphocytic choriomeningitis (LCM) virus, lymphocytes with the ability to develop in vitro into LCM virus-specific cytolytic clones were enumerated by use of the limiting dilution method. At intervals after virus inoculation, defined numbers of cells were cultivated with virus-infected syngeneic stimulator cells and T cell growth factor in multiple wells of microculture plates. After 7 days, individual cell cultures were tested for their ability to cause release of 51Cr from infected and uninfected syngeneic target cells. In cultures seeded with spleen cells from uninfected mice or from mice infected 3 days previously, no cytolytic activity was observed. On day 5, cells developing into LCM virus specific cytolytic effector cells were detected. They rose in numbers, and on days 8 to 9 after infection, values of approximately 1/10 and 1/200 in B6 and CBA mice, respectively, were calculated. A low proportion of microcultures proved cytolytic also for noninfected syngeneic target cells, but the counts thus released were consistently much lower than the counts set free from infected targets, and no regular dose-response relationships existed between seeded cells and positive cultures. Determination of cell surface antigens of responder cells by negative and positive selection procedures disclosed that they were predominantly T lymphocytes and expressed Lyt-2 but not L3T4 surface markers. Lysis by the great majority of LCM virus-specific clones was restricted by products of the major histocompatibility gene complex (MHC), but a few lysed, in addition, allogeneic infected or uninfected targets; however, a consistent pattern of alloreactivity was not observed. Furthermore, cells of a proportion of the cultures also lysed uninfected YAC cells. Probably this natural killer-like activity was acquired by T lymphocytes during prolonged cultivation. We conclude that most spleen cells that during acute infection with LCM virus attained the ability to develop in vitro into LCM virus-specific cytolytic clones were derived from MHC-restricted Lyt-2+, L3T4- antigen-specific cytolytic T lymphocytes and their activated precursors. PMID- 2886345 TI - Similarity of clozapine and SCH 23390 in reserpinized rats suggests a common mechanism of action. AB - Clozapine at doses up to 100 mg/kg p.o. did not antagonize apomorphine-induced stereotypy in vehicle pre-treated rats. However, if the animals were injected with reserpine (30 mg/kg i.p.) 24 h prior to the test, then clozapine (3-100 mg/kg p.o.) produced a dose-related blockade of apomorphine-induced stereotypy. The blockade of apomorphine-induced stereotypy in reserpinized rats by clozapine was attenuated by the D-2 selective agonist LY 171555 but not the D-1 selective agonist SKF 38393. This profile of agonist reversal of antagonist blockade of apomorphine-induced stereotypy seen with clozapine was identical to that seen with the selective D-1 antagonist SCH 23390. Presumably, the D-2 agonist was active because D-1 receptor systems were inhibited (either at the receptor or at some other post-synaptic site) by clozapine or SCH 23390; this allowed a partial restoration of apomorphine-induced stereotypy via the D-2 system. Therefore, these data indicate that clozapine and SCH 23390 share a common mechanism of action via D-1 receptor systems. PMID- 2886346 TI - Dynorphin A-(1-10) amide stimulates the release of atrial natriuretic polypeptide (ANP) from rat atrium. PMID- 2886347 TI - Increased antinociception by alpha-adrenoceptor drugs after spinal cord noradrenaline depletion. AB - Animals depleted of the bulbospinal NA fiber tracts have been reported to be supersensitive to antinociceptive effects of intrathecally administered noradrenaline (NA) in vivo. In the present investigation, the antinociceptive effects were determined after systemic or intrathecal injections of noradrenergic agents. NA and the selective alpha 2-adrenoceptor agonists guanfacine and clonidine were used. NA depletion was performed by treatment neonatally with 6 hydroxydopamine (6-OHDA), or in adult animals by intrathecal 6-OHDA administration or systemic N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4). The neurotoxins were found to cause a severe depletion of spinal NA without affecting dopamine (DA) or 5-hydroxytryptamine (5-HT) levels. The antinociceptive effects of intrathecal injection of NA, clonidine and guanfacine were more strongly enhanced in the depleted than in the control rats. It was also found that clonidine and guanfacine given systemically had a stronger effect in depleted than in control animals. In conclusion, depletion of descending NA pathways induces functional supersensitivity both to intrathecally administered NA and to the selective alpha 2-adrenoceptor agonists clonidine and guanfacine. It was also found that systemically administered clonidine and guanfacine had a stronger effect in NA-depleted than in control animals. PMID- 2886349 TI - Demonstration of the beta 2-adrenoceptor intrinsic efficacy of AY-28,925 using the PGF2 alpha-contracted guinea-pig trachea. AB - The abilities of AY-28,925, labetalol and medroxalol to relax the PGF2 alpha contracted isolated guinea-pig trachea have been investigated to compare their activities at beta 2-adrenoceptors. Maximum relaxation induced by AY-28,925 was significantly greater than that induced by either labetalol or medroxalol. This relaxation occurred in a concentration-dependent manner over a range of concentrations consistent with the previously determined affinity of AY-28,925 for beta-adrenoceptors. ICI-118,551 inhibited AY-28,925-induced relaxation in a concentration-dependent manner with a pA2 value similar to that determined for ICI-118,551 inhibition of the selective beta 2-adrenoceptor agonist salbutamol, but not the selective beta 1-adrenoceptor agonist norepinephrine. The Schild plot slope for ICI-118,551 inhibition of AY-28,925 or salbutamol did not differ significantly from unity, while that for inhibition of isoproterenol (a non selective beta-adrenoceptor agonist) did. It is concluded that AY-28,925 is a more efficacious relaxant of tracheal smooth muscle than either labetalol or medroxalol, and that this relaxant activity is the result of its greater intrinsic efficacy at the beta 2-adrenoceptor. PMID- 2886348 TI - Composite effects of actinonin when inhibiting enkephalin-degrading enzymes. AB - Actinonin which has been found to be an inhibitor of aminopeptidase M (EC 3.4.11.2) also inhibited enkephalinase A (EC 3.4.24.11) and enkephalin aminopeptidase which were partially purified from the corpus striatum membrane of guinea-pig brain. The IC50 values were 5.6 microM for enkephalinase A and 0.39 microM for enkephalin aminopeptidase. Actinonin also inhibited with an IC50 value of 1.1 microM dipeptidyl aminopeptidase tested on whole brain homogenate of rats in the presence of thiorphan and bestatin. Analgesia was assessed by measuring the tail-flick latency of mice. The analgesic effect of [Met5]enkephalin injected intracisternally (i.cist., 50 micrograms) was potentiated by an intraperitoneal (i.p., 100 and 300 mg/kg) as well as an i.cist. (25 micrograms) injection of actinonin. Actinonin was found to inhibit all three enzymes of enkephalin metabolism and, when given peripherally, to potentiate enkephalin analgesia. PMID- 2886350 TI - Spinal kappa-opioid receptor-mediated antinociception is stimulus-specific. AB - The intrathecal injection of a variety of selective kappa-opioid receptor ligands did not result in significant inhibition of thermal nociceptive tail flick responses in rats. In contrast, these compounds dose dependently inhibited pressure nociceptive responses. Cross-tolerance studies revealed that the kappa opioid receptor ligands tifluadom, U-50488H and dynorphin-(1-17) act upon a receptor distinguishable from the receptor through which morphine exerts its inhibition of mechanical nociceptive responses. The less selective kappa-opiate receptor ligands bremazocine and ethylketocyclazocine (EKC), however, blocked both tail flick and tail pressure nociceptive responses and their effect showed marked cross-tolerance to morphine in the tail flick nociceptive test, but not for the pressure nociceptive responses. We suggest that EKC and bremazocine act upon the spinal kappa-opioid receptor to block mechanical nociceptive responses but that the analgesic effect of EKC and bremazocine on thermal nociceptive responses is probably mediated via spinal micron- and/or delta-, and delta-opioid receptors, respectively. PMID- 2886351 TI - Role of a protein regulating guanine nucleotide binding in phosphoinositide breakdown and calcium mobilization by bradykinin in neuroblastoma X glioma hybrid NG108-15 cells: effects of pertussis toxin and cholera toxin on receptor-mediated signal transduction. AB - The addition of bradykinin to NG108-15 cells resulted in an increase in the intracellular Ca2+ concentration [( Ca2+]i) and the formation of inositol monophosphate, inositol bisphosphate, and inositol trisphosphate in these cells. The bradykinin-stimulated formation of inositol polyphosphates in plasma membrane preparations was dependent on the presence of GTP or guanosine-5'-O thiotriphosphate (GTP gamma S) but not of GDP. GTP gamma S, unlike GTP, increased the basal formation of inositol polyphosphate in NG108-15 membranes. Iontophoretic injection of GTP gamma S into single cells induced increases in [Ca2+]i. These effects of bradykinin and GTP gamma S on [Ca2+]i and the formation of inositol phosphates in the intact cells and membranes were not affected by treatment of the cells with pertussis toxin or cholera toxin. Data on binding of bradykinin to membrane preparations indicated the presence of two classes of binding sites with Kd values of 0.80 +/- 0.26 and 9.63 +/- 0.13 nM. Approximately 74% of the receptors were in the high affinity state. In the presence of guanyl 5'-yl-imidodiphosphate [Gpp(NH)p], the high affinity sites in the membrane preparations were converted to low affinity sites with no change in the total receptor number. These toxin treatments had no effect on binding of bradykinin to its receptors. Thus, these results indicate that a guanine nucleotide regulatory protein, which is not a substrate of pertussis toxin or cholera toxin, is involved in mediating the effects of bradykinin on membrane-bound phosphoinositide-specific phospholipase C to induce the increase of cytosolic calcium. PMID- 2886353 TI - Binding of [3H]SCH 23390 to dopamine D-1 receptors in rat retina in vitro. AB - [3H]SCH 23390 binding was examined in membranes of rat retina. The binding was saturable with a dissociation constant of 0.2 nM and the maximum number of binding sites was 236 +/- 74 fmol/mg protein. The pharmacology of [3H]SCH 23390 binding indicated that the binding was specific for a dopamine D-1 receptor because the binding was preferentially inhibited by D-1-selective agonists and antagonists but not by dopamine D-2-selective agonists and antagonists. The same membrane preparations were used to characterize the dopamine D-2 receptor binding as measured with [3H]spiperone and the amount of binding sites was found to be similar to the amount of D-1 sites. It is concluded that [3H]SCH 23390 is a useful tool to examine dopamine D-1 receptors in the retina. PMID- 2886352 TI - Cardiovascular effects of UD-CG 212 CL, a metabolite of pimobendan, in anaesthetized pigs. AB - Systemic and regional haemodynamic effects of UD-CG 212 CL (0.5-16 micrograms X kg-1 X min-1), the major metabolite of the vasodilator and cardiotonic drug pimobendan, were studied in anaesthetized pigs. The drug caused a dose-dependent decrease in left ventricular (LV) end-diastolic and arterial blood pressures while it increased systemic vascular conductance, heart rate and maxLVdP/dt. The decrease in LV end-diastolic pressure was observed at lower plasma concentrations than the increase in systemic vascular conductance. Cardiac output tended to decrease but statistical significance was achieved only with the highest concentration. These effects of UD-CG 212 CL were not altered by the blockade of beta-adrenoceptors with propranolol. The vasodilator action of UD-CG 212 CL was noticed in several organs but the effects were relatively more marked (in decreasing order of magnitude) in the adrenals, kidneys, gastrointestinal tract, brain and LV epicardium. Since both arterial pressure and cardiac output decreased, the blood flow increased significantly only in the adrenals and decreased moderately in the spleen, LV endocardium and skeletal muscles. The effects of UD-CG 212 CL on the renal and skeletal muscle haemodynamics were different from those of pimobendan, which causes vasodilatation in the skeletal muscles but not in the kidneys. The results of this study show that, like the parent compound pimobendan, UD-CG 212 CL has independent cardiotonic and vasodilator actions; the latter being more pronounced on the venous side. However, the contribution of this metabolite to the overall pharmacological activity of pimobendan appears to be limited. PMID- 2886354 TI - Effects of acute thioridazine, metoclopramide and SCH 23390 on the basal activity of A9 and A10 dopamine cells. AB - Extracellular single-unit recording techniques were employed to examine the effects of various dopamine (DA) antagonists on the basal activity of spontaneously active DA cells. Metoclopramide and thioridazine were both effective in reversing apomorphine-induced suppression of A9 and A10 DA cells. SCH 23390 produced only a partial reversal of this suppression. When the antagonists were given without any pretreatment, thioridazine preferentially increased the firing rate of A10 DA cells, and was relatively ineffective in altering A9 activity. Metoclopramide, on the other hand, increased the activity of most A9 DA cells, but was less effective in doing so with A10 cells. SCH 23390 did not significantly affect the basal activity of either cell subpopulation. These data support the hypothesis that the so-called 'atypical' antipsychotic drugs act preferentially on the A10 DA system. Taken together with previous results, they also suggest that the acute effects of DA antagonists on DA cell subpopulations coincide with their chronic effects. PMID- 2886355 TI - 3,4-Methylenedioxyethylamphetamine (MDE), a novel analogue of MDMA, produces long lasting depletion of serotonin in the rat brain. AB - The present study was carried out to asses possible toxic effects of 3,4 methylenedioxyethylamphetamine (MDE) on serotonergic, dopaminergic or noradrenergic neurons in the rat brain. It was found that MDE produced a long lasting, dose-related depletion of serotonin (5HT). However, even at high dosage, MDE did not reduce the concentration of either dopamine (DA) or norepinephrine (NE) on a long-term basis. When compared to 3,4-methylenedioxymethylamphetamine (MDMA), MDE was approximately one fourth as potent as producing a long-term depletion of 5HT. These results suggest that MDE, like MDMA, may be selectively toxic to central serotonergic neurons. PMID- 2886356 TI - BMY 7378, a buspirone analog with high affinity, selectivity and low intrinsic activity at the 5-HT1A receptor in rat and guinea pig hippocampal membranes. PMID- 2886357 TI - [Genetic monitoring of laboratory rat strains by restriction fragment length polymorphisms of mitochondrial DNA]. AB - Restriction fragment length polymorphisms of rat mitochondrial DNA (mtDNA) were examined using various kinds of laboratory rat strains in Japan. The results show that mtDNA of laboratory rats, Rattus norvegicus, are highly polymorphic; at least 7 types, Aa, Ba, Bb, Cb, Dc, Eb, and Fa, were found with the use of 6 restriction enzymes, EcoR I, Hind II, Hha I, Hpa II, Taq I, and Hinf I. Types Aa, Ba, and Eb were distributed widely in several strains, whereas types Ba, Cb, Dc and Fa were limited to some specific strains. These results indicate that restriction fragment length polymorphisms of mtDNA can be applied to genetic monitoring of laboratory rat strains. PMID- 2886358 TI - Dual effect of exogenous progesterone on the activity of tyrosine aminotransferase in the liver of female rats. AB - An as yet undescribed biphasic response of liver tyrosine aminotransferase (TAT) activity to a single administration of a microcrystallic watery suspension of 25 mg of progesterone (Agolutin Depot, SPOFA Praha) is described in adult female rats subjected to immobilization stress for 150 min. Exaggeration of the stress induced increase of TAT activity 3 and 8 h after hormone administration and its suppression 20 h after it was observed. The stress induced serum corticosterone increase is not correlated with the described changes, however, in non-stressed animals an increased TAT activity at 3 and 8 h after progesterone injection tightly follows the increased plasma corticosterone values. No statistically significant changes were found with respect to liver tryptophan pyrrolase activity. PMID- 2886359 TI - Entamoeba histolytica: chemoattractant activity for gerbil neutrophils in vivo and in vitro. AB - The kinetics of the host's cellular response in the peritoneal cavity of gerbils toward axenic pathogenic and nonpathogenic Entamoeba histolytica strains were examined. Amebae contained in diffusion chambers or free in the peritoneum elicited a neutrophilic response accompanied by decreased levels of macrophages and lymphocytes. Pathogenic amebae (IP:0682:1 strain) elicited a neutrophilic response greater than the nonpathogenic DKB and "entamoeba-like" Laredo amebae. The neutrophil eliciting factor was found in high levels in disrupted freeze thawed amebae (53% elicited neutrophils vs 8% for control), glutaraldehyde fixed amebae (45%) and amebic membranes (65%), and low levels in conditioned amebic medium (15%) and the supernatant fraction of amebae (16%). The factor was heat stable to high temperature (100 C for 30 min) and at various pH (6 to 9). The neutrophil eliciting factor in amebic membranes was lowered following pretreatment for 30 min with 1% immune and nonimmune gerbil or human sera (34-48% lowered neutrophil response vs control), acidic pH (less than 3, 69%), proteolytic digestion [trypsin (68%) and alpha-chymotrypsin (72%), 100 micrograms/ml], and 2% Triton X-100 (75%). Peritoneal neutrophils isolated following stimulation with amebic membranes or thioglycollate medium demonstrated higher chemotaxis in vitro toward live pathogenic amebae and amebic membranes (IP:0682:1 strain) compared to either the supernatant fraction or the nonpathogenic DKB or Laredo amebae. The results of this study indicate that membrane bound proteins of pathogenic amebae are chemotactic for gerbil neutrophils which may be important in the pathogenesis and pathology of amebiasis. PMID- 2886361 TI - [Effect of anaprilin on the tyrosine hydroxylase activity of the oral mucosa in dogs with experimental stomatitis]. AB - It was shown that in dogs with experimental aphthous stomatitis (ligation of the common bile duct) tyrosine hydroxylase activity and content of catecholamines (CA) in the oral mucosa were increased. Blockade of beta-adrenoreceptors caused by anaprilin (1 mg/kg) led to the further increase of tyrosine hydroxylase activity. A relative decrease of CA content was simultaneously observed. PMID- 2886362 TI - [Problems in the drug prevention of the seasickness syndrome (motion sickness)]. PMID- 2886363 TI - [Circadian changes in the pharmacokinetics and effects of fenazepam in rats]. AB - It was established that phenazepam is excreted from the rat blood several times more rapidly when administered at night. In this case the minimal pharmacological effect is observed as to various actions. During the drug administration in the morning and evening hours the greatest effect is observed that correlates well with the maximal concentrations of the drug after its administration at this time. PMID- 2886364 TI - [Synthesis of new diheterocyclic derivatives of imidazole with antiparasitic activity]. AB - A description is given of potential cyclic imidazoles such as 3,3-dichloro-2 methylenimino-acrylonitrile derived from nitro or non-nitro heterocycles, as well as the hydrazone, semicarbazone and arylpropenone derivatives of the 4-chloro-2 (5-nitro-2-thienyl) (V), 5-imidazole carboxaldehyde (IV) and the 5-bromothienyl analogue. The antiparasitic activity was tested in vitro against Trichomonas vaginalis and Entameba histolytica. Some of the nitro containing compounds showed trichomonacidal activity whereas one of the non-nitro compounds with potential imidazole structure showed clear amebacidal activity. This compound, 3,3-dichloro 2-methyleneimino acrylonitrile has anti-ameba activity comparable with that of metronidazole. PMID- 2886360 TI - Cytopathogenicity of Entamoeba histolytica: the role of amebic adherence and contact-dependent cytolysis in pathogenesis. AB - The mechanisms by which Entamoeba histolytica trophozoites adhere to and lyse target cells are reviewed from the perspective of pathogenesis. Adherence via the galactose and N-acetyl-galactosamine inhibitable amebic lectin and possible additional amebic adhesin molecules is followed by target cell death. Inhibition of the Gal/GalNAc lectin with GalNAc inhibits amebic cytolysis of target cells. Amebic activities implicated in the cytolytic event include vesicle exocytosis and maintenance of an acid pH, pore forming proteins, phospholipase A and proteases. Increased knowledge of the sequence of events leading to target cell lysis should lead to more effective treatment or prevention of infection by this enteric parasite and add to our basic understanding of eukaryotic cell-cell interactions. PMID- 2886365 TI - The stalk connecting the F1 and F0 domains of ATP synthase visualized by electron microscopy of unstained specimens. AB - E. coli F1F0 ATP synthase has been reconstituted into membranes and visualized by electron microscopy of unstained samples preserved in thin layers of amorphous ice. Unlike previous observations in negative stain, these specimens are not exposed to potentially denaturing or perturbing conditions, having been rapidly frozen from well-defined conditions in which the enzyme is fully active. The structures visualized in views normal to the lipid bilayer clearly show the presence of a narrow stalk approx. 45 A long, connecting the F1 to the membrane embedded F0. PMID- 2886366 TI - Participation of adenosine 5'-triphosphate in the activation of membrane-bound guanylate cyclase by the atrial natriuretic factor. AB - The addition of ANF to Percoll-purified liver plasma membranes produced a slight activation of guanylate cyclase; the ANF-stimulated cyclase activity was further increased upon the addition of ATP to the enzyme assay mixture. The effect of ATP to potentiate the cyclase activation was concentration-dependent, required Mg2+ as a divalent cation, and was seen with membranes from various tissues and cells. ATP increased the maximal velocity of the cyclase without a change in the affinity for GTP or ANF. Phosphorylation by ATP might not be involved since ANF stimulated guanylate cyclase was enhanced by non-phosphorylating ATP analogues as well. Thus, an allosteric ATP binding site is suggested to participate in ANF induced regulation of membrane-bound guanylate cyclase. PMID- 2886367 TI - Cyclin (PCNA, auxiliary protein of DNA polymerase delta) is a central component of the pathway(s) leading to DNA replication and cell division. AB - Cyclin, also known as PCNA or the auxiliary protein of mammalian DNA polymerase delta, is a stable cell cycle regulated (synthesized mainly in S-phase) nuclear protein of apparent Mr 36,000 whose rate of synthesis correlates directly with the proliferative state of normal cultured cells and tissues. Cyclin (PCNA) is absent or present in very low amounts in normal non-dividing cells and tissues, but it is synthesized in variable amounts by proliferating cells of both normal and transformed origin. All available information indicates that this ubiquitous and tightly regulated DNA replication protein is a central component of the pathway(s) leading to DNA replication and cell division. PMID- 2886369 TI - [Continuity in the work of women's consultation departments in central district hospitals and feldsher-midwife centers]. PMID- 2886368 TI - Clathrin beta-light chain of rat liver coated vesicles is phosphorylated in vitro and in vivo. AB - Clathrin beta-light chain of rat liver coated vesicles is phosphorylated in vitro in the presence of poly(L-lysine) by an endogenous protein kinase which appears to be similar to casein kinase II. Clathrin beta-light chain is also phosphorylated in vivo. After injection of [32P]phosphate into rats and preparation of purified coated vesicles in the presence of phosphatase inhibitors, electrophoretic analysis showed the presence of several labeled polypeptides including clathrin beta-light chain. A polypeptide of 50 kDa, which may correspond to the major polypeptide phosphorylated in vitro of coated vesicles, is also labeled in vivo. PMID- 2886370 TI - [The health corner]. PMID- 2886372 TI - [Systematic soldering of palladium-containing fired alloys]. PMID- 2886371 TI - [Organization of preventive and health and epidemic-control measures at feldsher midwife centers]. PMID- 2886373 TI - Salvaging the restoration. AB - Current concepts of salvaging large restorations and repairing crowns have been presented. Repair of restorations in the mouth is indicated in specific instances. The procedures described, when properly used, can result in a considerable savings both in time and expense to the dentist and the patient. PMID- 2886374 TI - Successful outcome of pregnancy in a subfertile patient with severe aortoarteritis (Takayasu's disease). AB - This report describes the successful outcome of pregnancy in a 27-yr-old subfertile Chinese nullipara with severe Takayasu's disease. Pregnancy was achieved following ovulation induction with clomiphene. Blood pressure was controlled with propranalol and fetal growth was monitored by serial ultrasound fetal anthropometry. Pregnancy was terminated at 38 weeks of pregnancy by elective caesarean section. A live female infant weighing 2420 g was delivered. PMID- 2886375 TI - Influence of testicular secretions on differentiation in the rat epididymis: ultrastructural studies after castration, efferent duct ligation and cryptorchidism. AB - The differentiation of the rat epididymis was studied in prepubertal castrated, ligated or cryptorchid rats, in order to assess the influences of blood-borne and luminal androgens. The principal cells showed partial differentiation: decrease in cell height, decreased numbers of cytoplasmic organelles implicated in the elaboration phenomena (Golgi apparatus, smooth endoplasmic reticulum), whereas the organelles implicated in the absorptive function remained relatively intact. The lamina densa of the basement membrane underlying the epithelium was irregular, thicker than normal and followed the irregular outline of the basal parts of the epithelial cells. These changes were evident in castrated rats, to a lesser degree in ligated and cryptorchid rats, and were more prominent in the initial part of the duct. On the other hand, the narrow cells and the clear cells followed a normal differentiation pattern in the experimental rats, suggesting that a differential androgen dependence exists among the various type of epididymal cells. PMID- 2886376 TI - gamma-Glutamyltranspeptidase in dimethylbenz[a]anthracene-induced mammary adenocarcinomas and in livers of tumor bearing rats. AB - A single dose of dimethylbenz[a]anthracene (DMBA) at 20 mg/kg resulted in 100% incidence of intraductal mammary adenocarcinomas in Wistar rats, the large tumors averaging 1.87 +/- 0.45 g. gamma-Glutamyltranspeptidase activities were elevated in DMBA-induced mammary adenocarcinomas relative to lactating mammary tissue in all fractions examined: 18.8-fold in homogenates; 22.1-fold in particulate fractions; and 5.7-fold in supernatant fractions. In DMBA-induced mammary adenocarcinomas, gamma-glutamyltranspeptidase was 95% particulate, 5% supernatant, whereas in lactating mammary tissue, gamma-glutamyltranspeptidase was equally distributed between particulate and supernatant fractions. Particulate gamma-glutamyltranspeptidase from DMBA-induced mammary adenocarcinomas as well as lactating mammary tissue displayed classical Michaelis Menten characteristics: for the adenocarcinoma enzyme Km was 2.5 nM and Vmax 200 nmol mg-1 min-1; for mammary tissue enzyme Km was 2.5 nM and Vmax 11.1 nmol X mg 1 X min-1. Both particulate enzymes were activated at 50 degrees C relative to 37 degrees C to the same extent: 1.37-fold. The activities of gamma glutamyltranspeptidase were increased 1.8-fold in the livers of rats bearing DMBA induced mammary adenocarcinomas relative to age-matched controls. Plasma levels of gamma-glutamyltranspeptidase were also increased 1.6-fold in tumor bearing rats. There was no observable sign of liver damage in tumor bearing rats; plasma glutamic pyruvic transaminase levels were normal in these animals. Blood glucose levels were elevated 17% in rats bearing DMBA-induced mammary adenocarcinomas compared to age-matched controls, although plasma insulin levels were the same in both groups: 35.4 +/- 3.5 microIU/ml for the former; 31.9 +/- 3.1 microIU/ml for the latter. PMID- 2886377 TI - International colloquy on the management of intrauterine fetal death. AB - Management of intrauterine fetal death is a common medial problem. The risks of time-related development of consumptive coagulopathy and intrauterine infection with speticemia force the clinician to terminate pregnancy as soon as possible while still taking into account the mental distress of the patients. Rapid surgical intervention (e.g. hysterotomy) is associated with a considerable risk of maternal morbidity and mortality. The following reports from international experts present a topical survey of current methods for the management of fetal demise. This background of clinical experience from different countries should serve to stimulate discussion on problems associated with intrauterine fetal death and ultimately lead to practical advice that will be of benefit to the patients. PMID- 2886378 TI - Childbirth following primary cesarean section--evaluation of a scoring system. AB - Of 1184 cases with previous cesarean section, 590 were selected for trial of vaginal delivery and 594 for repeat cesarean section. Of the former group, 76.6% had successful vaginal delivery. Incidence of uterine wound dehiscence and of perinatal mortality was highest in cases with primary classical cesarean section. Factors like indications for previous cesarean section, history of intercurrent vaginal delivery, weight of baby and period of gestation had positive correlation with delivery outcome. PMID- 2886379 TI - Factors associated with clinical reactions to rubella vaccination in women. AB - Two types of rubella vaccine were given to 272 seronegative healthy Japanese adult women. Clinical and laboratory studies on clinical reaction after vaccination were carried out on HI antibody response, HLA types, basal body temperature (BBT), menstrual cycles and serum progesterone levels of vaccinees. Clinical reactions were not associated with HLA types of vaccinees, but arthropathy occurred significantly more often in women vaccinated at the progestational stage than in women vaccinated at the estrogenic stage. PMID- 2886380 TI - The correlation of serum estrogens and androgens with bone density in the late postmenopause. AB - A pilot group of 16 women in the late postmenopause were evaluated for bone density by computerized axial tomography (CT) scanning and for hormonal milieu. A highly statistically significant positive correlation between lumbar-3 spongiosum density and both dehydroepiandrosterone-sulfate (DHEA-S), r = 0.67; P less than 0.005 and androstenedione (A), r = 0.56; P less than 0.03 was found. No such correlations were observed with estradiol (E2), estrone (E1) or an array of other hormones. The results of this preliminary report indicate a clear association of weak androgens with bone density in the late postmenopause. PMID- 2886381 TI - Colposcopic findings of gland openings in cervical carcinoma: their histological backgrounds. AB - During the past 8 years 1501 colposcopies were performed paying a special attention to cervical glands for diagnosis of cervical intraepithelial neoplasia (CIN) and carcinoma. Normal openings could exclude these diseases at the error rate of only 5.1%, while atypical openings could identify them at the high confidence rate of 96.3%. False positive evaluations were mostly attributable to a marked degree of squamous metaplasia in the glands. The absence of gland openings in the main portion of the lesions amounted to 88.6% in invasive carcinomas but to only 12.4% in CIN. Adenoma malignum was a highly characteristic exception. PMID- 2886382 TI - A lifetable analysis of sterilization failure: data from the Profamilia Clinic, Bogota, Colombia. AB - Sterilization failure rates were computed using lifetable methods for sterilizations occurring between 1973 and 1982 in the Profamilia family planning clinic in Bogota, Colombia. Out of a total of nearly 45,000 sterilizations occurring during this period 503 sterilization failures were detected. Comparing methods, laparoscopy with the silastic band method had a significantly higher rate of failure, 1.5% after 5 years compared to 0.9% for laparoscopy with cautery and 0.6% for minilaparotomy. PMID- 2886383 TI - In vitro studies on the control of human myometrial gap junctions. AB - In this study human myometrial tissues were examined for the presence of gap junctions by quantitative electron microscopy before and after incubation in tissue culture media with and without indomethacin. The area of gap junctions was very low in tissues from pregnant women at term but not labor, before incubation. After 24 and 48 h incubation without any treatment, segments of some of the same tissues developed many gap junctions and other tissues contained few junctions. Prostaglandin E (PGE), prostaglandin F (PGF) and prostaglandin F metabolite (PGF metabolite) levels in the media at various times were measured by radioimmunoassay. The prostaglandins increased progressively during the incubation period. Treatment of tissues with indomethacin decreased prostaglandin levels in the media and increased the numbers of gap junctions in those control tissues that developed few junctions over the same incubation interval. We conclude that the capacity of human myometrial tissues to develop gap junctions in vitro may depend upon a maturational stage in preparation for labor. Furthermore, our results suggest that products of the cyclo-oxygenase or lipoxygenase pathways may control the presence of gap junctions in the human myometrium and that changes in synthesis in these patterns may occur as part of the maturational process. PMID- 2886384 TI - Genital amebiasis. AB - Five cases of amebiasis of the genital tract involving the cervix, vulva and penis are described. All presented as an ulcerating mass and were clinically suspected to have a tumor. In two cases the amebiasis co-existed with a carcinoma, an association which is extremely rare. The spouse of a patient with penile amebiasis was found to have amebiasis of the cervix suggesting a sexually transmitted mode of infection. The need for histopathological confirmation of all suspected genital malignancies is emphasised due to the striking resemblance of genital amebiasis to a carcinoma. The co-existence of amebiasis with carcinoma is of interest and suggests a possible etiological relationship. PMID- 2886385 TI - Receptor-mediated adenylate cyclase-coupled mechanism for PGE2 inhibition of insulin secretion in HIT cells. AB - Prostaglandin E2 (PGE2) inhibits glucose-induced insulin secretion, and inhibitors of PGE2 synthesis augment this event. However, there has been confusion regarding prostaglandin regulation of insulin secretion, partly because no mechanism has been demonstrated for the inhibitory action of PGE2 on beta-cell function. These studies were performed with a clonal cell line of glucose responsive beta-cells (HIT cells) to determine whether PGE2 effects on insulin secretion are receptor mediated and, if so, whether the postreceptor effects are mediated by inhibitory regulatory components (Ni) of adenylate cyclase. Saturable [3H]PGE2 binding to HIT cells was demonstrated. This binding was dissociable and specific for prostaglandins of the E series. Scatchard analyses of binding data indicated a single class of sites with a Kd of approximately 1 X 10(-9) M. Guinea pig islets were also demonstrated to have a single class of binding sites with a similar Kd but only 22% as many binding sites (0.060 vs. 0.013 pmol/mg protein, HIT cells vs. guinea pig islet). HIT cells were demonstrated to synthesize PGE2, and this synthesis was inhibitable by acetylsalicylic acid. Accumulation of cAMP by HIT cells was inhibited in a concentration-dependent manner by PGE2 with an IC50 of approximately 1 X 10(-9) M. Insulin secretion by HIT cells during static incubations with 11.1 mM glucose was also inhibited by PGE2 in a concentration dependent manner with an IC50 of 1 X 10(-9) M. PGE2 was more potent than epinephrine but less potent than somatostatin in this regard. Maximum inhibition of glucose-induced insulin secretion was 26, 37, and 29% of control values for somatostatin, PGE2, and epinephrine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886386 TI - Effects of calcitonin gene-related peptide (CGRP) on islet hormone secretion in the pig. AB - Calcitonin gene-related peptide occurs in intrapancreatic nerves and endocrine cells. The peptide is therefore a candidate for being of physiological importance for pancreatic function. We examined the direct effects of calcitonin gene related peptide on islet hormone secretion in the pig by infusing the peptide into the superior pancreatic artery. We found that 15 min intrapancreatic infusion of calcitonin gene-related peptide (22 pmol/min) decreased baseline pancreatic insulin output from 48 +/- 10 microU/min to 8 +/- 7 microU/min (p less than 0.01). Moreover, calcitonin gene-related peptide inhibited glucose-induced insulin secretion by 45% compared to controls (p less than 0.01), yet left terbutaline (beta 2-adrenoceptor)-stimulated insulin secretion unaffected. Furthermore, while being without effect on baseline glucagon output, calcitonin gene-related peptide potentiated terbutaline-induced glucagon secretion more than seven-fold (p less than 0.001). In contrast, the peptide did not affect baseline or stimulated pancreatic somatostatin output. We conclude that in pigs calcitonin gene-related peptide inhibits insulin secretion and potentiates glucagon secretion by direct effects on the pancreas that are not mediated by primary alterations in pancreatic somatostatin secretion. We suggest that the neuropeptide calcitonin gene-related peptide might be of importance for the intrapancreatic regulation of insulin and glucagon secretion in pigs. PMID- 2886387 TI - [Peptic ulcer: current therapy]. PMID- 2886388 TI - Modification of hepatic proteins in rats exposed to high oxygen concentration. AB - The effect of high concentrations of oxygen on cellular proteins was examined in hepatocytes isolated from rats exposed to 100% oxygen for 0, 24, 48, or 54 h. Previous studies have demonstrated that protein oxidation mediated by mixed function oxidase systems is accompanied by the formation of protein carbonyl derivatives that can be detected by the formation of protein hydrazone derivatives on treatment with 2,4-dinitrophenylhydrazine (DNPH). In these studies the levels of DNPH-reactive proteins increased steadily during 48 h of continuous oxygen treatment and then decreased to control levels by 54 h. Although the specific activity of two hepatic enzymes, glutamine synthetase and glucose-6 phosphate dehydrogenase, decreased during oxygen treatment, antibody titration of each enzyme indicated that the levels of immunological cross-reactive protein either remained constant or increased slightly during 48 h of oxygen treatment. After 54 h of oxygen exposure the levels of immunologically cross-reactive material were significantly reduced. These results suggest that exposure of rats to high concentrations of oxygen leads to the oxidative inactivation of enzymes and the accumulation of oxidized proteins that are subsequently degraded. PMID- 2886389 TI - ATP-binding properties of P glycoprotein from multidrug-resistant KB cells. AB - The photoaffinity reagent 8-azido-alpha-[32P]ATP was used to label a protein of 170 kDa in membrane vesicle preparations from a highly multidrug-resistant cell line, KB-V1, but not from the drug-sensitive parental cell line KB-3-1. The 170 kDa labeled protein was immunoprecipitated with a monoclonal antibody (MRK-16) to P glycoprotein. Both ATP and GTP inhibited labeling by 8-azido-alpha-[32P]ATP. Labeling of P170 was not inhibited by 5 mM ADP, 5 mM ribose-5-phosphate, or 100 microM vinblastine. These data directly demonstrate that P glycoprotein has a nucleotide-binding site that could supply energy for drug transport. PMID- 2886390 TI - Calcium-dependent proteases: an enzyme system active at cellular membranes? AB - Proteases having a neutral pH optimum and an absolute requirement for calcium ion are found in virtually all mammalian cells. Association of calcium-dependent proteases and a specific inhibitor protein with biological membranes seems to be an important regulatory feature of this proteolytic system, and it is likely that membranes are preferred sites for calcium-dependent protease action. Several recent hypotheses for the physiological function of calcium-dependent proteolysis are consistent with a membrane-associated protease action. Calcium-dependent proteases may participate in cell membrane fusion: the proteolysis of membrane proteins, which is required for the efficient fusion of erythrocytes, may be catalyzed by these enzymes. There is also evidence for the involvement of calcium dependent proteolysis in postsynaptic membrane remodeling in the hippocampus after long-term potentiation. Although the relationship of the proteolysis to synaptic function is not known, it could have important physiological or pathophysiological consequences. Finally, it has recently been suggested that calcium-dependent proteolysis may be a physiologically significant mechanism for activating membrane-associated protein kinase C after exposure of some cell types to phorbol esters or other mitogens. Further pursuit of these hypotheses may reveal a novel role for intracellular calcium-regulated proteolysis in membrane associated cell functions. PMID- 2886391 TI - Molecular biology in physiology. AB - The aim of this symposium on molecular biology in physiology was to introduce molecular biology to physiologists who had relatively little exposure to the new developments in this field, so that they can become conversant on this topic and contribute to the advancement of physiology by incorporating molecular biological approaches as a part of their research arsenal. After the discussion of the basic concepts, terminology, and methodology used in molecular biology, it was shown how these basic principles have been applied to the study of the genes encoding two membrane proteins that have important transport functions (band 3 and ATPase). The second half of the symposium consisted of papers on the state-of-the art developments in the application of molecular biology to the studies of the atrial natriuretic factor and renin genes, adenylate cyclase-coupled adrenergic receptors, acetylcholine receptors and sodium channel, and long-term and short term memories. The ultimate goal is that these examples will provide an impetus for the opening of new frontiers of research in physiology by taking advantage of the tools developed from recent advances in molecular biology. PMID- 2886392 TI - [Changes in liver enzymes during treatment with diltiazem. Description of 2 cases]. AB - The authors report two cases of altered hepatic enzymes during diltiazem administration, in whom the derangement of enzymatic pattern developed some weeks after therapy was started. The withdrawal of the drug was followed by rapid normalization of enzymatic values. PMID- 2886393 TI - Localization of enkephalins and other endogenous opioids in the digestive tract. PMID- 2886394 TI - Peripheral actions of opiates in canine gastrointestinal tract: actions on nerves and muscles. PMID- 2886395 TI - [Pharmacokinetic interaction of histamine H2 receptor antagonists: mechanism and clinical implications]. PMID- 2886396 TI - Effects of TRH on hypothalamic catecholaminergic and serotoninergic neurons. AB - The in vivo and in vitro effects of TRH on tyrosine hydroxylase activity and on endogenous levels of noradrenaline as an index of noradrenergic neurons activity were studied in rat hypothalamus. The hydroxylation of tryptophan and the liberation of 5-hydroxyindole acetic acid were analyzed as an index of serotoninergic activity. TRH had no effect on tyrosine hydroxylase from hypothalamic homogenates in concentrations up to 100 ng/ml. Neither was the hydroxylation of tyrosine in intact hypothalamus. The TRH (4 micrograms/kg) decreased 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine accumulation after 10 min, and no effect on serotonin and noradrenaline concentrations was observed. TRH decreased endogenous levels of 5-hydroxyindole acetic acid by 35%. Thus, the results show that TRH or TSH might play a role in a short-loop feedback action involving catecholaminergic and serotonergic nerve terminals that regulate the liberation of TRH. PMID- 2886397 TI - Effects of somatostatin-25 and urotensin II on lipid and carbohydrate metabolism of coho salmon, Oncorhynchus kisutch. AB - Salmon (Oncorhynchus kisutch) somatostatin (sSS; 4 or 8 ng/g body wt) or synthetic Gillichthys urotensin II (UII; 2 or 4 ng/g body wt) were injected intraperitoneally into juvenile freshwater coho salmon. Both sSS and UII caused a dose-dependent increase in plasma free fatty acids (FFA) which diminished with time. sSS induced an initial (1 hr) transient hyperglycemia. By contrast, UII tended to induce hypoglycemia, this effect being significant 5 hr after injection of the higher dose. Both sSS and UII depressed plasma insulin titers 1 hr after injection. By 3 hr, the sSS-associated insulin depression was no longer observed. UII treatment induced a hyperinsulinemia which was present 3 and 5 hr after peptide administration. Although no decreases in liver total lipid concentration or in mesenteric fat total tissue mass were observed, lipolytic enzyme activity within each depot was significantly enhanced by both peptides. Neither sSS nor UII altered 3H2O incorporation into fatty acids or neutral lipids. However, enhanced lipogenesis, particularly by UII, was indicated by increased NADPH production resulting from glucose-6-phosphate dehydrogenase activity. Both sSS and UII enhanced glucose mobilization, as indicated by decreased liver glycogen content and increased liver glucose-6-phosphatase activity. UII, but not sSS, stimulated glycogen synthetase activity. These results suggest that both sSS and UII stimulate hyperlipidemia by enhancing depot lipase activity and that although both factors are potentially gluconeogenetic, sSS seems to be glycogenolytic and hyperglycemic, whereas UII may channel glucose to FFA synthesis. PMID- 2886399 TI - Benzodiazepine hypnotics--their use and abuse. PMID- 2886398 TI - Apolipoprotein genetic variation in the assessment of atherosclerosis susceptibility. AB - Apolipoproteins are the protein constituents of lipoproteins, the particles that transport cholesterol and triglycerides in the plasma. Numerous epidemiologic studies have associated variations in plasma levels of lipoproteins and apolipoproteins with the development of atherosclerosis. Furthermore, genetic variations in lipoproteins and apolipoproteins have been associated with disorders of lipid metabolism. Recent advances in biochemical and molecular genetic methods have resulted in an increased understanding of interindividual variations in lipoprotein metabolism and of their relationship to atherosclerosis and the dyslipoproteinemias. In particular, certain DNA restriction fragment length polymorphisms of the apolipoprotein genes have, in the last few years, been associated with atherosclerotic diseases and dyslipoproteinemias. We believe that genetic markers, when used in conjunction with traditional clinical and biochemical determinations, may one day be useful in predicting atherosclerosis susceptibility in the general population. PMID- 2886400 TI - Nucleotide sequence of the glutamine synthetase gene and its controlling region from the acidophilic autotroph Thiobacillus ferrooxidans. AB - A 2089-bp chromosomal DNA segment containing the Thiobacillus ferrooxidans glnA gene has been sequenced. Putative glnAp1-type promoter sequences, a consensus ntrC-gene-product-binding site and a catabolite-activating protein consensus recognition sequence were detected upstream of the structural gene. The glnA gene was followed by a sequence resembling a Rho-independent termination sequence. The complete amino acid sequence (468 residues) of the glutamine synthetase (GS) has been deduced, and comparisons are made with reported amino acid sequences of GS from other organisms. PMID- 2886401 TI - Cloning and expression of rat homeo-box-containing sequences. AB - Six rat homeo-box-containing DNA sequences have been isolated by screening a genomic library with a probe derived from an Antennapedia (Antp) cDNA clone of Drosophila melanogaster. Sequence determination of two of the clones containing the homeo-box regions reveals a 180-nucleotide(nt) domain sharing more than 80% homology at the nucleotide level and more than 90% homology at the amino acid level with the homeo-box from the Antp gene and from homeo-boxes of other metazoan species. Genomic blotting experiments suggest that the two homeo-box containing DNA regions are present in one or two copies per haploid rat genome. Northern blot analysis of RNA has shown that the rat homeo-box sequences are expressed in a tissue-specific manner; transcripts were detected in the spinal cord and kidney, but not in brain, testis, liver, and spleen. The rat nucleotide sequences lying outside the 180-nt homeo-box domain share virtually no sequence homology with the Antp flanking regions. However, one clone does show an equally high degree of amino acid homology within the homeo-box and its immediate flanking region with a putative homologous gene in mouse. The result suggests that some of the mammalian homeo-box-containing genes are conserved in evolution and may serve important cellular or developmental functions. PMID- 2886403 TI - Bibliotherapy for depressed older adults: a self-help alternative. PMID- 2886402 TI - Visible corneal nerve fibers and neuromas of the conjunctiva--a syndrome of type 3 multiple endocrine adenomatosis in two generations. AB - A case report of multiple mucosal neuroma syndrome (multiple endocrine adenomatosis type 3) is presented in a mother and her two children. In all of them the eye involvement consisted of highly visible corneal nerves, neuromas of the conjunctiva, and thickened eye lids. The mother had mucosal neuromas of the tongue, and in the 4-year-old girl these were seen to appear during the follow-up period. The mother and children had medullary carcinoma of the thyroid. Marfanoid physiognomy was also one characteristic clinical feature. PMID- 2886404 TI - Study of brain capillary neuronal regulation as a tool to investigate cerebral asymmetries. PMID- 2886405 TI - Anorexia nervosa and depression: a common biochemical pathogenesis? PMID- 2886407 TI - Pharmacological treatment of epilepsy today. AB - The pharmacological treatment of epilepsy has not gone through remarkable changes in recent years. Treatment is based on few first choice drugs, the mechanism of action of which we do not yet know exactly. These include: phenobarbital, primidone, phenytoin, carbamazepine, valproic acid, ethosuximide, clonazepam. Choice of drug is determined by the kind of seizures presented by the patient, while successful treatment is determined by the kind of epilepsy. The present trend is the use of first line drugs in monotherapy, fixing individually the dosage according to the plasma levels. The results obtained with the GABA agonists (progabide, gamma-vinyl GABA) and with some of the calcium-antagonists (flunarizine) seem promising. PMID- 2886406 TI - Excitatory amino acid signal transduction in cerebellar cell cultures. AB - In primary cultures of cerebellar granule cells excitatory amino acid recognition sites are coupled with the stimulation of inositol phospholipid (PI) hydrolysis, cGMP formation and 45Ca2+ uptake. Mg2+, 2-amino-5-phosphonovalerate (APV) and phencyclidine (PCP) potently inhibit signal transduction in response to N-methyl D-aspartate (NMDA), glutamate (GLU) and aspartate (ASP). Activation by quisqualate (QUIS) is transduced selectively into stimulation of PI hydrolysis and this response is not sensitive to inhibition by Mg2+, APV and PCP. Activation by kainate (KA) is transduced into potent stimulation of cGMP formation and 45Ca2+ uptake. Transduction of KA signal is not affected by Mg2+ and is relatively insensitive to PCP and APV. PMID- 2886409 TI - [Secondary prevention of myocardial infarction with beta-blockers: for how many?]. PMID- 2886408 TI - [Neuroendocrine control of the female menstrual cycle]. PMID- 2886410 TI - [Sipple syndrome or multiple endocrine neoplasia type IIA]. PMID- 2886411 TI - [Effects of intravenous and intracerebroventricular terazosin, prazosin and clonidine on spontaneous sympathetic outflow in rats]. AB - The hypotensive activity of terazosin has been attributed to inhibition of postsynaptic alpha-1 adrenoceptors. The present study examined the influence of terazosin on spontaneous sympathetic outflow in anesthetize and immobilized rats. The effects on blood pressure and heart rate were also evaluated. Intravenously (i.v.) injected terazosin 0.3 mg/kg and prazosin 0.1 mg/kg increased a sympathetic outflow by 15.4 and 21.6%, respectively. These drugs produced a significant and long-lasting fall in blood pressure with slight heart rate change. On the contrary, clonidine 0.1 mg/kg, i.v. significantly inhibited the sympathetic outflow by 69.2%. The intracerebroventricularly administered 10 micrograms/kg clonidine also showed the sympathoinhibitory effect. However 3 micrograms/kg, i.c.v. of terazosin and prazosin increased the sympathetic tone by 16 and 7.2%. During these periods, in both drugs slightly decreased the blood pressure. These changes in hemodynamic parameters and nerve activities were obtained at 2 approximately 3 min after the i.c.v. administration. The 10 micrograms/kg, i.c.v. of terazosin and prazosin significantly inhibited the pressor response by phenylephrine 1 micrograms/kg, i.v. These results indicate the peripheral effect of terazosin and prazosin through the penetration of the drugs from the brain. The results provide evidence that terazosin, like prazosin, dose not affect cardiovascular regulation by a central action. PMID- 2886412 TI - [Smoldering adult T-cell leukemia complicating severe respiratory failure--an autopsy case report]. AB - An autopsy case of smoldering adult T-cell leukemia (ATL) is presented. 67 year old woman was admitted to our hospital with complaints of fever, cough and increasing dyspnea on October 2, 1985. Laboratory findings revealed high LDH, azothermia and slightly leukocytosis with low percentage of flower cells. CRP was strongly positive. Gas disturbance was markedly. Anti-ATLA antibody using indirect immunofluorescence method was X40 positive. Subsets of peripheral lymphocytes showed OKT 4 dominant. (OKT 3; 67.5%, OKT4; 60.6%, OKT8; 8.8%). A chest X-ray film revealed cardiomegaly and fine granular shadows in bilateral lower pulmonary fields. Diagnosis of interstitial pneumonitis was defined in transbronchial lung biopsy (TBLB) specimen. O2 therapy, steroid therapy added antibiotics were ineffective, respiratory failure and renal failure were progressive, she died by septic shock in 39th hospital days. In autopsy, no characteristic histological changes of ATL were found in lymph node, bone marrow, spleen, liver, kidney and lung. Sepsis was the cause was of death. Finally this case diagnosed smoldering ATL and pulmonary fibrosis due to bronchial ectasia with repeated pulmonary bacterial infections. The pulmonary complications of patients with ATL were discussed. PMID- 2886413 TI - Effect of estradiol upon serum enzymes in primary biliary cirrhosis. AB - The repeated observation of a fall in serum enzymes at midmenstrual cycle in an untreated patient with primary biliary cirrhosis stimulated a study of estrogen administration in five patients with primary biliary cirrhosis. One patient was premenopausal, one patient was postmenopausal and three had had oophorectomy. After 2 weeks of ethinyl estradiol, AST was under 100 IU per dl in all and had decreased by 50% or more in 4 of 5 patients. gamma-glutamyltransferase and alkaline phosphatase fell by 50 and 30% or more, respectively, in all patients. The decreases in serum enzymes were statistically significant in all patients for gamma-glutamyltransferase, in 4 of 5 for AST and in 3 of 5 for alkaline phosphatase. One patient developed increased icterus leading to withdrawal of estradiol. Withdrawal of estradiol was followed by return toward control values over variable periods, usually 1 to 4 weeks. Repeated courses of estradiol reproduced these enzyme changes. These observations indicate that estradiol in the doses used (0.05 mg per day) reversibly lowers serum enzyme values in biliary cirrhosis. The mechanism of the effect is unexplained, but an immune system alteration may be responsible. PMID- 2886414 TI - Corticotropin-releasing factor has an anxiogenic action in the social interaction test. AB - The effects of intracerebroventricular (icv) injections of corticotropin releasing factor (CRF, 100 and 300 ng) were investigated in the social interaction test of anxiety in rats. Both doses of CRF significantly decreased active social interaction without a concomitant decrease in locomotor activity. CRF also significantly increased self-grooming, an effect that was independent of the decrease in social interaction. These results indicate an anxiogenic action for CRF. Chlordiazepoxide (CDP, 5 mg/kg ip) pretreatment reversed the anxiogenic effects of icv CRF (100 ng), but CRF did not prevent the sedative effects of CDP. There were no statistically significant changes due to CRF in locomotor activity or rears or head dipping in the holeboard test. Both doses of CRF significantly increased plasma concentrations of corticosterone. The possible mechanisms of the behavioral effects of CRF are discussed. PMID- 2886415 TI - Response of rats to the presence of stressed conspecifics as a function of time of day. AB - The physiological response of nonrestrained rats to the presence of immobilized conspecifics during the beginning of the active period and the inactive period was studied. In immobilized animals concentrations of serum corticosterone (SCS), serum glucose, and liver glycogen, and the activity of liver tyrosine aminotransferase (TAT) during both the active and the inactive periods, were consistent with earlier studies. In nonrestrained rats the presence of immobilized conspecifics induced a significant increase in SCS during the active period, whereas it had no effect during the inactive period. The level of TAT was significantly elevated in the nonrestrained rats only during the inactive period and remained unchanged during the active period. The results demonstrate a physiological influence of stressed rats on unstressed conspecifics and provide evidence for regulation of TAT activity that is dependent on the situation and the time of day. PMID- 2886416 TI - NIMH report. The gene hunt. PMID- 2886417 TI - Drug interactions. PMID- 2886418 TI - Localization of the ornithine aminotransferase gene and related sequences on two human chromosomes. AB - We have used a full length cDNA clone to determine the chromosomal location of the gene encoding human ornithine aminotransferase (OAT), a mitochondrial matrix enzyme. Southern blot analysis of Sca I-digested DNA from 34 human-mouse somatic cell hybrids revealed 11 human fragments. Three fragments mapped to chromosome 10q23-10qter, confirming the previous provisional assignment of the functional gene to this autosome by analysis of OAT expression in somatic cell hybrids (O'Donnell et al. 1985). The remaining eight fragments were assigned to the X chromosome, and regionally assigned to Xp21-Xp11 by use of an X-chromosome mapping panel. These X chromosome sequences could represent pseudogenes, or related members of a multigene family. Two of the X chromosome fragments are alternate alleles of a restriction fragment length polymorphism (RFLP) making this OAT-related locus an excellent genetic marker. The RFLP may now be used to determine any possible relationship between this locus and several X-linked eye defects. PMID- 2886419 TI - A new HindIII restriction fragment length polymorphism in the hemophilia A locus. AB - Using a fragment of the cDNA for human coagulation factor VIII as a hybridization probe, we have detected a new polymorphic HindIII site in intron 19 of the factor VIII gene. The frequency of the minor allele is 0.30. This polymorphism shows strong linkage disequilibrium with a previously described BclI polymorphism in intron 18. PMID- 2886421 TI - Linkage relationships and allelic associations of the cystic fibrosis locus and four marker loci. AB - The linkage relationships between the cystic fibrosis (CF) locus and four marker loci (MET-H, MET-D, D7S8 and D7S16), allelic associations between these loci and the extent of informativity at these marker loci were investigated in a sample of 206 families with at least one child affected by CF. The data were contributed by 11 laboratories from Europe and Israel. The maximum lod scores and recombination frequency estimates (luminal diameter) (and confidence limits of luminal diameter) were: 18.3 at luminal diameter = 0.007 (0.001-0.038) for CF vs. MET, 11.0 at luminal diameter = 0.016 (0.001-0.068) for CF vs. D7S8, and 5.7 at luminal diameter = 0.0 (0.0-0.064) for CF vs. D7S16. A gene order of CF-MET-D7S8 was best supported by the data, but its preference to the order D7S8-CF-MET is mainly based on one single family. There are significant allelic associations between CF, MET, D7S8 and D7S16; these allelic associations affect the risk of random individuals to be carriers of CF. PMID- 2886420 TI - Three cases of 45,X/46,XYnf mosaicism. Molecular analysis revealed heterogeneity of the nonfluorescent Y chromosome. AB - Three patients with 45,X/46,XYnf mosaicism were investigated by Southern hybridization using both X- and Y-specific DNA probes. Our patients seem to be hemizygous for the X chromosomal loci tested. Single-copy and low-copy repeated Y chromosomal sequences assigned to the short arm, centromere, and euchromatin of the long arm have been detected in our patients, suggesting the Y chromosomal origin of the marker chromosome both in male and female cases studied. Densitometry of autoradiographs revealed a double dose of Yp-specific fragments of the DXYS1 locus. None of the patients tested showed either the 3.4- or the 2.1 kb Hae III male-specific repeated DNA sequences. It seems likely that the Ynf is a pseudodicentric chromosome with duplication of Yp and euchromatic Yq sequences, the Yq heterochromatin being lost. Our findings indicate structural heterogeneity of the marker chromosome and in addition provide further information on the relative position of DNA sequences detected by DNA probes 50f2, M1A, and pDP105. PMID- 2886422 TI - Maternal origin of a de novo balanced t(21q21q) identified by ets-2 polymorphism. AB - Molecular investigations were done in a woman with a de novo balanced t(21q21q) discovered because of the birth of a trisomic 21 baby. Polymorphisms detected with probe ets-2 after Msp I digestion showed that both chromosomes 21 involved in the rearrangement were of maternal origin. The most likely hypothesis is that of a disomic 21 oocyte fertilized by a nullisomic 21 sperm. PMID- 2886423 TI - Action of atrial natriuretic peptide on cyclic GMP system in vascular smooth muscle. PMID- 2886424 TI - Restriction fragment length polymorphism of the human T cell receptor alpha gene. I. Two polymorphic restriction sites localized to different regions of the gene. AB - Previous studies have demonstrated restriction fragment length polymorphisms (RFLP) in the vicinity of the alpha and beta genes of the human T-cell receptor. In the course of experiments designed to discover additional polymorphic restriction sites, we found a new RFLP of the T-cell alpha gene recognized by the restriction enzyme Taq I. The site was localized to the interval between the most 3' joining (J) exon and the most 5' constant (C) region exon, about 7 kb distant from the previously described Bgl II polymorphic site which mapped to the vicinity of the 3' untranslated exon. With the use of these two polymorphic markers, four Ti-alpha alleles could be identified, allowing unambiguous assignment of all Ti-alpha genes in some families. These markers may be useful in identifying possible immune response genes or disease predisposition genes associated with the genes of the T-cell receptor for antigen. PMID- 2886425 TI - Allelic variants of Ly-5 in inbred and natural populations of mice. AB - Allelic variants of Ly-5 in inbred commensal and other natural populations of mice were analyzed by patterns of restriction fragment length polymorphisms (RFLP) and Southern hybridization using an Ly-5 cDNA probe and by cell-surface staining with a panel of antibodies directed against polymorphic and nonpolymorphic Ly-5 determinants. New Ly-5 alleles were defined by RFLPs generated by both Eco RI and Bam HI restriction enzyme digests. The Mus musculus subspecies and other species within the genus Mus showed a strong correlation between allelic variants defined by restriction enzymes and serologic specificities. The data also suggest the conservation of the Ly-5 gene throughout the genus Mus. PMID- 2886426 TI - Analysis of class II genes of the chicken MHC (B) by use of human DNA probes. AB - Class II genes of the major histocompatibility complex (MHC) in the chicken have been investigated by Southern blot analysis using human cDNA probes for DQ alpha, DQ beta, DR alpha, and DR beta. Both beta probes but not the alpha probes cross hybridized well with chicken DNA. The results indicated that the beta probes hybridized with at least two beta genes in the chicken MHC and there was no clear indication of a DQ-DR subdivision of chicken class II beta genes. The possibility of using human beta probes for MHC typing in the chicken was tested by using two homozygous individuals for each of 20 different, serologically defined, MHC (B) haplotypes originating from the domestic breeds of White Leghorn and Rhode Island Red, or from Red Jungle Fowl (the wild ancestral form). Genomic DNA samples from these individuals were digested with any one of the Eco RI and Pvu II restriction enzymes and hybridized with the DR beta probe. Restriction fragment length polymorphism (RFLP) was obtained with Pvu II only, which resolved seven different RFLP types. There was an excellent correlation between these RFLP types and the serological B typing since the RFLP type was identical within each pair of homozygotes. In addition to this broad survey of many haplotypes, a more detailed comparison was carried out on B21-like haplotypes originating from different breeds. No differences in restriction fragment patterns among these haplotypes could be resolved using any of the restriction enzymes Bg1 II, Eco RI, Hind III, Pst I, Pvu II, and Taq I. PMID- 2886427 TI - Structural and functional variability among DQ beta alleles of DR2 subtypes. AB - Homozygous lymphoblastoid cell lines representing various Dw subtypes of DR2 were examined for polymorphism at the DQ beta locus by molecular and cellular techniques. The subtypes studied included Dw2, Dw12, and a group heterogenous by cellular typing that we shall refer to as non-Dw2/non-Dw12. Restriction fragment length polymorphism analysis of cell lines representing these subtypes revealed DQ beta-specific patterns consistent with cellular typing. Two-dimensional gel electrophoresis of DQ molecules from representative cell lines revealed a structural polymorphism of DQ beta among the three subtypes. The DQ beta chain migrated to a position that was unique to each subtype and was consistent among various representative cell lines of each subtype. Nucleotide sequence analysis of cDNA clones of DQ beta from Dw2, Dw12, and non-Dw2/non-Dw12 lines confirmed that the variability resided at the genetic level. Variability was found in the form of numerous scattered nucleotide substitutions throughout the first domain of these alleles. The DQ beta gene of the non-Dw2/non-Dw12 cell line AZH was further found to be almost identical with the DQ beta gene of a DR1 line (Bell et al. 1985b), implicating a common evolutionary origin of these alleles. The only difference between these two sequences was due to an apparent gene conversion event at amino acid 57. T-cell cloning experiments resulted in the derivation of Epstein-Barr virus-specific, DQw1-restricted clones that proliferated against only those cell lines that exhibited the DQ beta gene common to AZH and the DR1 cell line. Thus, the polymorphism among DQ beta alleles within DR2 results in subtype-specific restriction. PMID- 2886428 TI - Isolation of Japanese encephalitis & West Nile viruses from mosquitoes collected in Kolar district of Karnataka state during 1977-79. PMID- 2886429 TI - A dark brown mutant of Bacillus thuringiensis H. 14 synthesising higher level of mosquito larvicidal factor. PMID- 2886430 TI - Role of pili in the adherence of Pseudomonas aeruginosa to mouse epidermal cells. AB - Pili have been demonstrated to be the adhesins of Pseudomonas aeruginosa for mouse epidermal cells. The mechanisms of adhesion of P. aeruginosa to mouse epidermal cells was studied by using four mutants derived from a single strain: flagellated and piliated (F+P+), flagellated and nonpiliated (F+P-), nonflagellated and piliated (F-P+), and nonflagellated and nonpiliated (F-P-) mutants. F+P+ and F-P+ bacteria efficiently adhered to mouse epidermal cells, while F+P- and F-P- bacteria hardly adhered to mouse epidermal cells. The number of F+P+ bacteria that adhered to mouse epidermal cells was almost the same as that of F-P+ bacteria. The number of F+P- bacteria that adhered to mouse epidermal cells was almost the same as that of F-P- bacteria. The adhesion of P+ (F+P+ and F-P+) bacteria was inhibited by antipilus serum, while that of P- (F+P- and F-P-) bacteria was not inhibited by antipilus serum. There were no significant differences between the number of bacteria adhering to mouse epidermal cells isolated from normal skin and those adhering to cells isolated from burned skin. Heating of the mouse epidermal cell suspension had no effect on the adhesion of P. aeruginosa. These results suggest that pili mediate the adhesion of P. aeruginosa to mouse epidermal cells and that P. aeruginosa adheres efficiently to mouse epidermal cells despite the loss of cell viability caused by burning. PMID- 2886431 TI - Surface properties of the Vero cytotoxin-producing Escherichia coli O157:H7. AB - Strains of Escherichia coli serotype O157:H7 are Vero cytotoxin-producing enteric pathogens which have been associated with sporadic cases and outbreaks of hemorrhagic colitis and with the hemolytic uremic syndrome in humans. In addition to toxin production, adherence of many pathogenic bacteria to intestinal mucosal surfaces is a critical primary step in the pathogenesis of diarrheal diseases. Although E. coli serotype O157:H7 organisms adhere to intestinal epithelia of orally infected animals in a pattern morphologically identical to that previously described in adherent, effacing E. coli infections, the mechanisms of bacterial adherence are not known. To determine the cell surface adhesins which mediate attachment of E. coli O157:H7 to epithelial surfaces, we evaluated the surface properties of these organisms. Five strains isolated from children with the hemolytic uremic syndrome were grown both in broth cultures and on agar media. Adherence and invasion of E. coli O157:H7 in Intestine 407 and HEp-2 epithelial cell lines was quantitated using an enteroinvasive E. coli strain (serotype O164:NM) as a control. Cell surface properties of E. coli O157:H7 were evaluated by agglutination of a series of erythrocytes, transmission electron microscopy, DEAE-ion-exchange chromatography, and hydrophobic interaction chromatography. E. coli O157:H7 strains adhered to but did not invade either Intestine 407 or HEp-2 cells. Homologous O157:H7 rabbit antiserum blocked attachment of bacteria to tissue culture cells, in contrast to heterologous antiserum and preimmune rabbit serum, which did not inhibit attachment of E. coli O157:H7. None of the five O15:H7 isolates mediated mannose-resistant hemagglutination under any of the in vitro culture conditions. One isolate mediated mannose-sensitive hemagglutination after serial passage in broth cultures. Pili and fibrillae were not visualized by electron microscopy on nonhemagglutinating organisms, but pili were demonstrated on the one isolate which mediated mannose-sensitive hemagglutination. All O157:H7 strains demonstrated high anionic surface charge (DEAE) but low surface hydrophobicity properties (hydrophobic interaction chromatography). The findings suggest that surface structures other than pili can mediate attachment of serotype O157:H7 bacteria to epithelial cells in vitro. PMID- 2886432 TI - Nonfimbrial, mannose-resistant adhesins from uropathogenic Escherichia coli O83:K1:H4 and O14:K?:H11. AB - Nonfimbrial, mannose-resistant hemagglutinins (nonfimbrial adhesions [NFA] NFA-1 and NFA-2) were extracted from two agar-grown urinary isolates of Escherichia coli strains 827 (O83:K1:H4) and 54 (O14:K?:H11). The proteins were purified to homogeneity by ammonium sulfate precipitation and column chromatography. Nonfimbrial adhesins are soluble proteins, which tend to form aggregates of molecular weight above 10(6). NFA-1 and NFA-2 consist of subunits of 21,000 and 19,000 molecular weight, respectively. Both hemagglutinins caused hemagglutination of human erythrocytes and bound to human kidney cell monolayers. The binding of bacteria and hemagglutinins was assessed by using suitable antisera as detectors in an enzyme-linked immunosorbent assay. NFA-1 and NFA-2 inhibited the adherence of their respective strains to human kidney cells in a linear dose response. NFA-2 also inhibited heterologous strain adherence, but NFA 1 did not. Hemabsorption of bacterial suspension with erythrocytes at 4 degrees C, followed by differential centrifugation, enabled us to obtain a bacterial suspension lacking nonfimbrial adhesins in the supernatant and an adhesin enriched bacterial suspension that was eluted from erythrocytes at 40 degrees C. Bacteria eluted from erythrocytes exhibited a higher adherence capacity than unfractionated cells. Bacteria of the fraction lacking adhesins did not adhere to human kidney cells. Electron microscope examinations showed the presence of an extracellular capsule-like layer in adhering E. coli 827, but not in nonadhering bacteria. E. coli 54 did not express the adhesin as a capsule. We conclude that E. coli 827 and 54 produce extracellular adhesins consisting of soluble proteins which are differently expressed and antigenically distinct. The adhesins seem to share a common receptor and mediate the adherence of two uropathogenic E. coli strains to epithelial cells. PMID- 2886433 TI - Analysis of colony-stimulating factors and macrophage progenitor cells in mice immunized against Listeria monocytogenes by adoptive transfer. AB - Experiments were performed to elucidate the role of colony-stimulating factors in host defenses to the intracellular pathogen Listeria monocytogenes. Mice were protected against Listeria sp. by adoptive transfer of immune spleen cells and were then challenged with listeriae intravenously. Control mice were injected with spleen cells from uninfected mice. Adoptively immunized (immune) mice had significantly fewer listeriae in spleens and livers 2 and 4 days after Listeria challenge than did control mice. During acute infection, colony-stimulating activity in serum was increased earlier (10 h) in immune mice than in controls. Concentrations of colony-stimulating activity were equal at 24 h. By 48 h, values were decreased in immune mice, but were elevated in control mice. Similar changes were noted when a specific colony-stimulating factor, macrophage colony stimulating factor, was measured in serum by using a radioimmunoassay. The changes in serum colony-stimulating activity in mice adoptively immunized with immune spleen cells were eliminated if spleen cells were first treated with anti Thy-1.2 monoclonal antibodies. The number of macrophage progenitor cells in bone marrow and spleen were also determined as measures of the hemopoietic potential in these organs. The number of macrophage progenitor cells in bone marrow was higher in immune animals than control animals at 1, 2, and 4 days of infection. Similarly, the number of these cells in spleens was higher during the early stages of infection in immune mice. These results indicate that both the regulation of leukocyte production and the transfer of specific cellular immunity by spleen cells are associated, and they therefore suggest that hemopoietic regulatory factors play a role in immune host defenses. PMID- 2886434 TI - Stimulation by target cell membrane lipid of actin polymerization and phagocytosis by Entamoeba histolytica. AB - The identity of molecules of mammalian target cells that stimulate contact dependent attack by Entamoeba histolytica was sought using human erythrocytes (RBC) as a model. Protein-free liposomes prepared from RBC membrane lipids stimulated the same rapid E. histolytica actin polymerization and phagocytosis as did whole target cells. Liposomes constructed from the major phospholipids of RBC stimulated these responses but only if a negatively charged phospholipid was included. The addition to these liposomes of digalactosyl diglyceride significantly enhanced their stimulatory activity. The results demonstrate that ligands that trigger attack-related responses by E. histolytica reside in the target cell membrane lipid fraction and suggest roles for both glycolipid and phospholipid components. PMID- 2886435 TI - Comparison of the genetic determinant coding for the S-fimbrial adhesin (sfa) of Escherichia coli to other chromosomally encoded fimbrial determinants. AB - DNA probes specific for different regions of the S-fimbrial adhesin (sfa) determinant were constructed and hybridized with DNA sequences coding for P (F8 and F13), mannose-sensitive hemagglutinating type 1 (F1A), and F1C fimbriae. While the sfa and F1C DNA determinants exhibited homology along their entire lengths, the P-fimbrial and type 1-fimbrial determinants exhibited homology to regions of the sfa cluster responsible for the control of transcription and, to a minor extent, to regions coding for proteins involved in biogenesis and/or adhesion of the fimbriae and for the N-terminal part of the fimbrillin subunit. PMID- 2886437 TI - Renal tolerance of cefpirome (HR 810), a new cephalosporin antibiotic. AB - An open study was carried out in ten healthy, male volunteers in order to investigate the renal tolerance of cefpirome (HR 810), a new cephalosporin antibiotic. Subjects received a single dose of 1.0 g of cefpirome and then repeated doses of 1.0 g of cefpirome twice daily for five days. Urine was collected in several fractions during the study and the urine excretion, excretions of creatinine, N-acetyl-beta-D-glucosaminidase, gamma glutamyltransferase, alanine aminopeptidase and lactate dehydrogenase were calculated in 12-hour fractions. Serum creatinine (using an enzymatic method), beta 2-microglobulin concentrations and creatinine clearance were also determined. Based on the findings of these renal enzymes, renal tolerance was good. This was also confirmed by creatinine clearance calculations and follow-up of serum beta 2-microglobulin levels. Cefpirome showed good renal tolerance without any signs of nephrotoxicity in this study with the methods used. PMID- 2886438 TI - Participation of cell-mediated immunity in allergic bronchopulmonary aspergillosis. AB - While IgE and IgG antibodies are thought to play important pathogenetic roles in allergic bronchopulmonary aspergillosis (ABA), the microscopic lung picture would implicate cell-mediated immunity. Patients with ABA do not manifest delayed skin test reaction to Aspergillus fumigatus (AF). This has been attributed to inhibition of lymphokines by histamine locally released as a result of the immediate skin test reaction. We tested 5 ABA patients for delayed hypersensitivity to AF. An attempt was made to ablate the immediate skin test reaction to determine if a delayed reaction might be unmasked. At concentrations of AF previously shown to produce marked immediate skin test reactions, the combination of cimetidine by mouth and chlorpheniramine mixed with AF in the skin test syringe completely eliminated the immediate skin test reaction in all 5 patients. In no case did a delayed reaction appear. Eight ABA patients showed in vitro lymphocyte stimulation responses to AF that were comparable to those of asthmatics and rhinitics with positive immediate skin test reactions to AF and no clinical evidence of ABA. It thus appears that 'peripheral' cell-mediated immune responses, namely delayed skin reactivity and peripheral blood lymphocyte proliferation to AF, are not present in ABA. PMID- 2886436 TI - Infectious diseases in Africa. PMID- 2886439 TI - The rat testis produces large amounts of an interleukin-1-like factor. AB - Homogenates of whole testis, isolated seminiferous tubules, testicular cytosol, conditioned media from seminiferous tubules obtained from intact or cryptorchid rats, as well as seminiferous tubules devoid of peritubular cells, showed high concentrations of interleukin-1 (IL-1). Cytosol from spleen showed low IL-1 activity, while no activity was found in cytosol from heart, kidney, prostate, ovary or liver. Interleukin-1 activity was not detected in spent medium from cultures of immature Sertoli cells (10-day-old rats) or from peritubular cells or in homogenates of interstitial cells from adult rats. Ultrogel AcA 44 gel chromatography and HPLC size exclusion chromatography exhibited a single peak of IL-1 activity corresponding to a relative molecular mass of 17,000-20,000 (Mr = 17-20 K). Similarly, chromatofocusing revealed only one peak of activity with an apparent isoelectric point of 5-6. It is concluded that the rat testis contains large amounts of an IL-1 alpha-like factor. The adult Sertoli cell or possibly germ cells are suggested as its primary source. Testicular IL-1-like activity is of particular interest in view of the intense cell proliferation during spermatogenesis, and the tendency to testicular relapse of acute lymphoblastic leukaemia. PMID- 2886440 TI - Abnormal infantile germ cells and development of carcinoma-in-situ in maldeveloped testes: a stereological and densitometric study. PMID- 2886441 TI - Monoclonal integration of HTLV-I proviral DNA in patients with strongyloidiasis. AB - The relationship between strongyloidiasis and HTLV-I was investigated in Okinawa, an area where both conditions are endemic. Thirty-six patients with strongyloidiasis were seropositive for HTLV-I and suffered from several related clinical complications. Fourteen of these patients (39%) were shown to have monoclonal integration of HTLV-I proviral DNA in their blood lymphocytes, a condition designated as "smouldering" adult T-cell leukaemia (ATL). Monoclonal integration of proviral DNA correlated with an increased CD4/CD8 ratio and the presence of abnormal lymphocytes in the peripheral blood, and with a trend for greater severity of the parasitic infection. Although the immunodeficiency caused by HTLV-I could predispose to hyperinfestation by Strongyloides, it is also possible that both the parasitic and the retroviral infestations are important co factors leading to the development of ATL. PMID- 2886442 TI - Photodermatoses in Lagos. AB - Light-sensitive dermatoses do not constitute a major problem among the black people in Nigeria. In a 10-year study, only 64 cases (about 0.4% of all dermatologic patients) had light-sensitive dermatoses. Seven of the 10 patients with endogenous photodermatoses were albinos. Two patients with polymorphic light eruption were visiting Caucasians. Only one normally pigmented black Nigerian had xeroderma pigmentosum. Fifty-four patients had photodermatoses from exogenous causes, of which hydroquinone-induced exogenous ochronosis constituted the largest group of patients. Two women had estrogen-induced porphyria cutanea tarda. PMID- 2886443 TI - Synthesis of a cyclic retro analogue of somatostatin suitable for photoaffinity labelling. AB - Cyclic somatostatin analogues containing the modified retro sequence of the amino acids Phe7 to Phe11 of the natural compound have been found to exhibit high activity for cytoprotection of rat hepatocytes against cell poisons such as phallotoxins and galactosamine. Cyclo(-Phe(p-NH(1-14C)Ac)-Thr-Lys(CO(p-N3)C6H4) Trp-Phe-D-Pro), a photoreactive and radioactive analogue of one of the most active cyclohexapeptides, was synthesized by a combination of solid phase technique and classical solution peptide synthesis. This peptide labels the same proteins in rat liver cell membrane that are modified by photolysable derivatives of bile acids, phalloidin and antamanide. PMID- 2886444 TI - Medical management of the depressed alcoholic patient. AB - Since the advent of modern psychopharmacology in the 1950s, use of medications in the treatment of many psychiatric disorders has become commonplace. Alcohol use is also widespread. As alcohol can interact with a wide variety of medications to alter drug effects, understanding the interactions between it and psychiatric medicines is important to the efficacious treatment of the depressed alcoholic with these drugs. This article briefly outlines the effects of alcohol and the mechanisms of its interactions with psychiatric medications. The most commonly used classes of psychiatric medicines, including antidepressants, CNS depressants, benzodiazepines, antipsychotics, psychostimulants, and lithium carbonate, are reviewed as to their potential interactions with alcohol. Clinical implications of these interactions are discussed. PMID- 2886445 TI - Modulation of messenger RNA metabolism in experimental methyl mercury neurotoxicity. AB - We have investigated the effects of methyl mercury of mRNA metabolism in mouse brain cells in vivo. It was demonstrated that methyl mercury substantially reduces the rate of synthesis of ATP and poly(A)-segments of mRNAs. The molecular sizes of poly(A)-segments isolated from hnRNA and polysomal mRNA of the experimental animal brain are smaller than the dimensions of the same segments from the cellular RNA of intact mice. A fall in the mRNA polyadenylation rate seen under methyl mercury directly correlates with reduced metabolic stability (t 1/2) of the respective poly(A)+mRNA. The mean time of nuclear-cytoplasmic transport of these mRNAs (t0 is substantially increased under methyl mercury. At the same time, methyl mercury has no effect on the metabolism of brain polysomal poly(A)-mRNA. Direct addition of methyl mercury to an in vitro system containing excess ATP failed to affect the activity of poly(A) polymerase isolated from the brain of intact mice. The poison-induced alterations in the poly(A)+mRNA metabolism bring about a considerable reduction of the poly(A)+-fraction's share in the total polysomal mRNA and dramatic fall in the intracellular polysomes concentration. All the alterations in the examined metabolic parameters well correlate both with a reduced ATP content in the brain tissue and decreased rate of total protein synthesis in brain cells. Proceeding from these results as well as data from the literature, we developed a hypothetical model of a general molecular mechanism whereby methyl mercury inhibits protein synthesis in the brain. PMID- 2886446 TI - Importance of endogenous substrates in synaptosomal functions. AB - Synaptosomes were found to contain endogenous substrates in sufficient amount to support physiological ion equilibrium and to maintain the resting oxygen consumption rate. Exogenous substrates were required only in functional states which brought about an increase of oxygen consumption only in the presence of a stimulating agent. Succinate increased oxygen consumption even in the resting phase but proved to be incapable of supplying energy for synaptosomal ion transport processes. PMID- 2886447 TI - [A patient with arterial hypertension and bilateral adrenal gland neoplasms]. PMID- 2886448 TI - Atriopeptin-activated guanylate cyclase in the anterior segment. Identification, localization, and effects of atriopeptins on IOP. AB - Atriopeptins are a recently-discovered group of polypeptides secreted from cardiac myocytes in response to fluid overload. The present studies demonstrate that atriopeptin receptors, coupled to the activation of guanylate cyclase, are present in rabbit ciliary process. Rat atrial natriuretic peptide 1-28 (rANP) activated ciliary process guanylate cyclase activity with a Vmax of from 24-337% and with a Ka of from 0.4-4 nM, similar to that for atriopeptin receptors present in rabbit kidney. Activation was greater for the intact peptide than for rANP fragments 1-11 or 13-28, and stimulated activity was greater in isolated ciliary processes than in ciliary muscle or iris. Intravitreal injection of the complete peptide into living rabbits caused a marked decrease in IOP in the ipsilateral eye which persisted for more than 48 hr and occurred without evidence of an inflammatory response. There was a smaller decrease in IOP in the contralateral eye. Following intravitreal injection of rANP 1-28, atriopeptin levels in aqueous humor remained elevated for at least 44 hr. Injection of the biochemically less active rANP fragments 1-11 and 13-28 caused no decrease in IOP. These physiological data, together with the biochemical identification of atriopeptin receptors and second messenger systems in the ciliary process, suggest that certain tissues of the anterior segment may be atriopeptin end-organs and that agents acting at atriopeptin receptors may be able to regulate IOP. PMID- 2886449 TI - Drug treatment for elderly patients. PMID- 2886450 TI - Buspirone: a new treatment for anxiety. PMID- 2886451 TI - Isozymes as host-donor blood cell "tracers" in bone marrow transplantation. AB - Prescreening of blood cells of prospective donors and hosts by simple electrophoresis for well-known polymorphic enzyme phenotypes offers markers to monitor the fate of bone marrow grafts in the hosts. Cellogel electrophoresis is handy for routine screening of red cell enzymes for polymorphic variants [Rattazzi et al, 1967; Meera Khan and Rattazzi, 1968; Meera Khan, 1971; Someren et al, 1974; Ebeli-Struijk et al, 1976; Meera Khan and Doppert, 1976; Meera Khan et al, 1982]. Highly sensitive methods for microelectrophoretic assays for phenotyping the individual enzyme systems, if they become available, will be of greater value than the conventional procedures. For PGM1 phenotyping, the procedure of isoelectric-focusing (IEF) [Winter et al, 1977] was found to be highly sensitive and gave the best resolution. Polymorphic variants of house keeping enzymes, by nature, can play the role of universal markers since they are expressed in individual types of the whole range of cells derived from hematopoietic and stromal cell precursors in the transplanted patients. Compared to chromosome analysis in dividing cells or screening for RFLP's detectable in unique DNA sequences, marker enzyme phenotyping by electrophoresis is methodologically simple, easy, quick, inexpensive, rapidly repeatable and equally reliable, requires only a small quantity of easily obtainable peripheral blood sample, and could monitor all lineages of blood cells including non-nucleated and nondividing cells. PMID- 2886453 TI - An immunohistochemical study of somatostatin in the ovine, porcine and rodent pineal gland. AB - Using anti-somatostatin in an immunoperoxidase technique at the light microscope level, somatostatin-like immunoreactivity was detected in ovine, porcine and rodent pineal glands. Positively stained cell bodies of various sizes and cellular processes were found throughout the glands. The chemical identity of this immunoreactive material and its physiologic significance remain to be determined. PMID- 2886452 TI - Immunohistochemical evidence of serotoninergic regulation of vasoactive intestinal polypeptide (VIP) in the rat suprachiasmatic nucleus. AB - By applying a double-immunolabeling technique to preembedded tissue preparations, we demonstrated the existence of serotoninergic innervation to neurons containing vasoactive intestinal polypeptide (VIP) in the rat suprachiasmatic nucleus (SCN). Immunoreactivity for serotonin and VIP was revealed by the presence of diaminobenzidine (DAB) reaction products and silver-intensified DAB reaction products, respectively; in a further stage, the silver grains were substituted with gold particles. DAB reaction products were precipitated on the surface of vesicular structures, while gold particles were scattered diffusely throughout the neuroplasma at various densities. Serotoninergic axons were numerous and closely packed together, occasionally forming synaptic junctions with gold labeled VIP-containing neurons. At these synaptic junctions, small vesicular structures accumulated to form a coat under the presynaptic membrane, and the postsynaptic membrane was lined with a homogeneous accumulation of fine deposits. This postsynaptic apparatus varied in appearance; some parts were flat and thin, while others were of irregular thickness. Serotoninergic fibers also formed synaptic junctions with unidentified neurons, in which postsynaptic membrane specialization was also observable. As VIP-containing neurons are known to be synapsed by somatostatin (SRIH)-containing neurons, their regulation must involve both serotonin and SRIH at least. PMID- 2886454 TI - Effect of collidine (2,4,6-trimethylpyridine) on the osmiophilia and chromaffin reaction in the synaptic vesicles of rat pineal nerves. AB - Rat pineal nerve endings contain a population of small and of large synaptic vesicles that are either electron lucent or have electron-dense cores. It has been reported that their osmiophilia is eliminated when collidine buffer is used in the fixation procedure. We investigated this effect and found that osmium tetroxide and potassium dichromate reactivity were abolished when excised pineal glands were briefly incubated with collidine buffer before glutaraldehyde cacodylate fixation. Such an effect was not observed when collidine was applied after fixation. Glands that had been fixed in glutaraldehyde or osmium tetroxide buffered with collidine exhibited a peripheral zone containing reactive synaptic vesicles and a deeper, central zone where such reactivity was absent. These results indicate that the effect of collidine is due to depletion of monoamines rather than to chemical blockage of their reactivity, and further suggest that collidine has a higher rate of penetration into tissues than the tested fixatives. PMID- 2886456 TI - Eosinophilic fasciitis. 171 cases reviewed. PMID- 2886455 TI - Immunohistochemical detection of ganglia in the rat stomach serosa, containing neurons immunoreactive for gastrin-releasing peptide and vasoactive intestinal peptide. AB - Ganglia, not previously described, were identified in the rat stomach serosa along the minor curvature. The ganglia consisted of varying number of cell bodies lying in clusters along or within nerve bundles. The ganglia were shown to contain GRP and VIP immunoreactive nerve fibers and cell bodies and also some NPY immunoreactive fibers, whereas they were devoid of somatostatin immunoreactivity. Nerve ligation experiments indicated that the ganglia are intrinsic to the stomach. PMID- 2886457 TI - Noonan's syndrome. With carcinoma of undescended testis. PMID- 2886458 TI - New law to increase organ donations. PMID- 2886459 TI - Organ transplantation. PMID- 2886460 TI - Criteria for organ donors. PMID- 2886461 TI - Dealing with AIDS. The need for physician education. PMID- 2886462 TI - ISMS actions regarding AIDS. PMID- 2886463 TI - Clinical treatment of AIDS. Waiting for the other shoe to drop. PMID- 2886464 TI - AIDS and the law. PMID- 2886465 TI - Surgeon General speaks out on AIDS. PMID- 2886466 TI - The acquired immunodeficiency syndrome. Issues for hospital and medical staffs. PMID- 2886468 TI - Public health authorities' challenge. Battling AIDS' deadly threat. PMID- 2886467 TI - AMA advocates criteria for selective HIV antibody testing. PMID- 2886469 TI - IDPH survey of Illinois adults. Awareness and attitudes about AIDS. PMID- 2886470 TI - Referral dilemmas. PMID- 2886471 TI - Infant sex sequences. PMID- 2886472 TI - The other side. PMID- 2886473 TI - Job hunting. Part Two. PMID- 2886474 TI - Oculodento-osseous syndrome in a newborn infant. PMID- 2886475 TI - Synergistic armamentarium for schizophrenia treatment. PMID- 2886476 TI - Seeking the colon polyp. PMID- 2886478 TI - Do you know them as well as they know you? PMID- 2886477 TI - Immunocompetence assessment. PMID- 2886479 TI - Acquired immunodeficiency syndrome: issues for hospitals and medical staffs. PMID- 2886480 TI - On quality of life. PMID- 2886481 TI - Cervical microflora of pelvic inflammatory disease. PMID- 2886482 TI - Localized prostatic cancer. PMID- 2886483 TI - Isolation of Clostridium perfringens from neonatal calves with ruminal and abomasal tympany, abomasitis, and abomasal ulceration. AB - Eight neonatal calves (2 to 21 days old) with suspected abomasal displacement or intestinal obstruction after acute onset of abdominal tympany, colic, depression, or death were referred to Kansas State University for clinical examination or for necropsy. Results of routine hematologic and serum chemical analyses did not reveal consistent changes. Necropsy revealed abomasal distention, with various degrees of abomasitis, hemorrhage, and ulceration, but did not reveal evidence of displaced abomasum or obstructed intestine. Specimens of ruminal contents collected via stomach tube or at necropsy and abomasal contents collected at necropsy were obtained for anaerobic bacteriologic culture. Clostridium perfringens was isolated from all specimens, and on the basis of toxin neutralization tests in mice, 7 were type A and one was type E. Copper concentrations in serum and tissues were within normal limits. It appeared that the acute abdominal syndrome in these neonatal calves was unrelated to copper deficiency, and that C perfringens, particularly type A, may have had an appreciable contributory role in its pathogenesis. PMID- 2886484 TI - Effects of experimental cryptorchidism and subsequent orchidopexy on seminiferous tubule functions in the lamb. AB - The reversibility of damage caused by cryptorchidism to the seminiferous tubules of the lamb was investigated at various ages. Lambs were made bilaterally cryptorchid either at birth or at 2 months of age. Then orchidopexy was performed at either 2 or 4 months of age. In permanently cryptorchid lambs, spermatogenesis stopped completely, and Sertoli cell function, as measured by FSH receptors, androgen receptors and ABP, was much reduced (-96%, -86% and -81%, respectively). Orchidopexy allowed the cryptorchid seminiferous epithelium to grow again, but the more differentiated the germ cells, the less they were capable of restoration. Even in 0- to 2- and 0- to 4-month-old temporarily cryptorchid lambs that had recovered normal Sertoli cell function, 16 to 49% of the tubules still were empty. It was concluded that cryptorchidism irreversibly damages the seminiferous tubules at a level other than the hormone receptors. PMID- 2886486 TI - Effects of subminimal inhibitory concentrations of antibiotics on the adherence of Pseudomonas aeruginosa to tracheobronchial mucin. AB - Bacterial adherence to mucins may be important in tracheobronchial infections in cystic fibrosis. Sublethal concentrations of antibiotics reduce bacterial adherence to epithelial cells and mucins. This reduction in adherence may be a component of antimicrobial effects in infections at anatomical sites where bactericidal concentrations of antibiotics are difficult to achieve. We therefore tested the effects of sublethal concentrations of an aminoglycoside, tobramycin, and a beta-lactam antibiotic, ceftazidime, on the adherence of Pseudomonas aeruginosa to tracheobronchial mucin, since mucus secretions are often colonized by P. aeruginosa in cystic fibrosis. Adherence of the mucoid strains tested was inhibited by ceftazidime, but not by tobramycin. This effect of ceftazidime may partially explain its efficacy in patients with cystic fibrosis despite variables achieved in sputum. PMID- 2886487 TI - Determination of reserpine and rescinnamine in Rauwolfia serpentina preparations by liquid chromatography with fluorescence detection. AB - A method is presented for the determination of reserpine and rescinnamine in Rauwolfia serpentina powder or tablets by liquid chromatography (LC) with fluorescence detection. The sample is dispersed in CH3OH, 0.5N H2SO4 is added, and the mixture is extracted with five 30 mL portions of CHCl3. The extracts are separated from interfering materials on a Celite-0.1N NaOH column, and the eluates are collected in 50 mL CH3OH. After complete removal of the CHCl3, reserpine and rescinnamine are determined by liquid chromatography on a normal phase column with CH3OH as the mobile phase. Because reserpine and rescinnamine produce a single peak, chromatograms are obtained at different wavelengths. Reserpine is determined at an excitation wavelength of 280 nm and an emission wavelength of 360 nm. Rescinnamine is determined at an excitation wavelength of 330 nm and an emission wavelength of 435 nm. Recovery studies were conducted at 2 different levels to simulate 100 and 50 mg Rauwolfia serpentina tablets. Samples of Rauwolfia serpentina powders and tablets were also examined, and the results were compared with those obtained by the current AOAC official method. The proposed method is applicable to the analysis of ground composites and individual tablets. PMID- 2886485 TI - Effects of adrenergic agonists and insulin on porcine adipose tissue lipid metabolism in vitro. AB - Because this laboratory has been able to demonstrate only a small and somewhat inconsistent stimulation of glucose metabolism by insulin in porcine adipose tissue in vitro, the tissue was preincubated with insulin to attempt to enhance the hormone effect. Preincubation with or without insulin did not increase insulin stimulation. Furthermore, insulin did not stimulate triacylglycerol biosynthesis. Adrenergic hormones stimulated lipolysis in porcine adipose tissue in vitro. Several analogs of norepinephrine incubated with porcine adipose tissue in vitro did not inhibit glucose incorporation into CO2 or total lipids, in contrast to inhibition observed in adipose tissue from other species. Isoproterenol inhibited glycerol-3-phosphate incorporation into lipids; the maximal inhibition was 50% for the initial stages of the pathway. Palmitate incorporation into lipids also was inhibited 50% by isoproterenol but this may have been an artifact. Preincubation of adipose tissue, with no exogenous hormone, might decrease the concentration of endogenous adrenergic hormones and thus make the tissue more responsive to exogenous adrenergic hormones. Preincubation of porcine adipose tissue did not consistently lower the basal lipolytic rate but enhanced the stimulated lipolytic rate; the mechanism is not known. These experiments provide no evidence that preincubation is beneficial to measurement of lipolysis or glucose metabolism in porcine adipose tissue in vitro. PMID- 2886488 TI - Proton magnetic resonance spectroscopic determination of bethanechol chloride in tablets. AB - A simple and reliable proton magnetic resonance spectroscopic method was developed for the assay of bethanechol chloride in tablets. The proposed method entails a minimum of procedural steps and reagents. The recovery of bethanechol chloride from synthetic formulations was 99.9 +/- 0.4% (n = 15), CV = 0.4%. Mean assay values for 25 and 10 mg commercial tablets were 100.5% (n = 8) and 99.7% (n = 7) of declared, respectively. A detailed interpretation of the proton magnetic resonance spectrum is also presented. PMID- 2886489 TI - Clinical and morphological severity of renal involvement in systemic necrotising vasculitides. PMID- 2886490 TI - Fimbrial phase variation in Escherichia coli: dependence on integration host factor and homologies with other site-specific recombinases. AB - Expression of fimA, the structural gene for type 1 fimbriae of Escherichia coli, is phase variable. Significant homologies were identified between the recombinases which control fimbrial phase variation, FimB and FimE, and the integrase class of site-specific recombinases. Normal expression of fimA was shown to require the integration host factor (IHF). Mutations in either the himA or the himD (hip) gene, which encode the alpha and beta subunits of IHF, respectively, prevented phase variation and locked expression of fimA in either the "on" or "off" phase. In addition, both himA and himD lesions caused a sevenfold reduction in expression of a phi(fimA-lacZ) operon fusion in strains in which fimA was locked in the on phase. Thus, IHF plays a dual role in controlling fimA expression: it is required both for inversion of the fimA control region and for efficient expression from the fimA promoter. A mechanism by which IHF may exert control over fimA expression is discussed. PMID- 2886492 TI - Idiosyncratic neuroleptic response. PMID- 2886491 TI - Neuroleptic malignant syndrome: physiological and laboratory findings in a series of nine cases. AB - A series of nine cases of neuroleptic malignant syndrome (NMS) are presented with peak measures of autonomic dysfunction and laboratory findings. Urine abnormalities, consisting of proteinuria, casts, or cells, were an associated finding in these cases. Severe hypophosphatemia was present in two patients. Relative dehydration before the onset of the syndrome in eight of the nine patients supports the suggestion that it is a risk factor for the development of NMS. The withdrawal of dopamine agonists was also seen as a trigger for NMS. Autonomic instability and muscular rigidity occurred separately in some cases. Creatine phosphokinase elevation and fever did not necessarily parallel the duration or the degree of muscular rigidity, and this finding supports the idea of a central cause for the symptoms. A systematic approach is presented for the evaluation and treatment of NMS. Observations implicate central dopaminergic mechanisms in the regulation of autonomic functioning and the maintenance of peripheral muscle membrane stability. PMID- 2886493 TI - Psychopharmacology of borderline personality disorder: a review. AB - Borderline personality disorder poses a significant treatment challenge to the clinician. The frequent presence of comorbid disorders and the occurrence of a wide array of possible target symptoms complicate clinical assessment. Limited data from controlled clinical trials suggest that neuroleptics, monoamine oxidase inhibitors, and the anticonvulsant carbamazepine produce statistically and clinically significant short-term symptom reduction and may be useful components of the treatment approach to borderline personality disorder. Further research is needed to identify subgroups of patients with borderline personality disorder who are particularly responsive to a given medication and to explore the possibility that specific symptom complexes (such as suspiciousness, anhedonia, affective lability, or behavioral dyscontrol) are preferentially responsive to specific agents. PMID- 2886494 TI - Neuroleptic treatment in the borderline patient: advantages and techniques. AB - A low-dose neuroleptic strategy is indicated in borderline personality disorder as an acute treatment for symptoms of anger, hostility and suspiciousness, referential thinking and paranoid ideation, anxiety and dissociation, depressed mood, and related behavioral dyscontrol. Medication effects are clinically significant although modest in magnitude. Recommended duration of treatment is generally brief (3-12 weeks), although continued pharmacotherapy may be warranted in selected cases. The risks of treatment include the well-recognized side effects of neuroleptics (minimized by low doses) and the possibility of abuse, overdose, or interaction with alcohol or street drugs. Pharmacotherapy is seen as an adjunct to supportive psychosocial intervention. PMID- 2886495 TI - Treatment of outpatients with borderline personality disorder. AB - Outpatient treatment of patients with borderline personality disorder is sometimes more difficult and more challenging than inpatient treatment. Because symptoms are frequently less florid and more variable in the outpatient, diagnostic evaluation must proceed at a slower pace. Diagnostic distinctions among patients with borderline personality disorder are based on whether the predominant symptoms displayed are "affective," "schizotypal," or "impulse disordered." Outpatient evaluation requires a keen sensitivity to the presenting problems and the ability to assign priorities to treatment issues. Pharmacotherapy can be of advantage in treating outpatients with borderline personality disorder, but care must be taken in selecting appropriate drugs and dosage and in communicating to the patient what can be expected during therapy. Borderline patients with impulse-control disorders, especially substance abuse, cannot be treated effectively with individual psychotherapy alone. Although many creative and articulate psychodynamic formulations of borderline personality disorder have been proposed, an initial "cognitive" approach to psychotherapy combined with pharmacotherapy can be effective in alleviating acute symptoms, and more psychodynamic approaches can be employed when the patient is better equipped to use them. PMID- 2886496 TI - Possible involvement of acetyl coenzyme A carboxylase as well as fatty acid synthetase in the temperature-controlled synthesis of fatty acids in Saccharomyces cerevisiae. AB - Fatty acid synthetase (FAS) preparations from Saccharomyces cerevisiae cells grown at either 35 or 10 degrees C produced the same products at different temperatures and showed quite similar temperature-dependencies in Arrhenius plots, with break points at 25 degrees C. This break point does not appear to reflect a phase transition of phospholipids present in the purified FAS preparations but rather is associated with protein conformational changes. S. cerevisiae cells grown at 35 degrees C and then shifted to 10 degrees C produced fatty acids with a shorter average chain length than those fatty acids synthesized at 10 degrees C by cells already adapted to 10 degrees C (hyper response). Acetyl-CoA carboxylase activity was relatively higher in the cells grown at 35 degrees C than in the cells grown at 10 degrees C; moreover, fatty acids with longer average chain lengths were synthesized in vitro at higher malonyl-CoA concentrations, which was consistent with the difference in the average chain lengths of newly synthesized fatty acids in cells grown at 35 and 10 degrees C. However, the activity levels of acetyl-CoA carboxylase and fatty acid synthetase alone did not account for the hyper response phenomena. PMID- 2886497 TI - Structure and expression of pea mitochondrial F1ATPase alpha-subunit gene and its pseudogene involved in homologous recombination. AB - We have characterized four pea mitochondrial DNA segments carrying the F1ATPase alpha-subunit coding sequences. These four types share a common 1.7-kb repeat sequence flanked by four combinations of two different left- and right-hand sequences. These results suggest that the alpha-subunit genes locate at the homologous recombination sites in the pea mitochondrial genome and that homologous recombination between two of these loci generates the other two types of structures. The uninterrupted alpha-subunit coding sequence of 1,521 bp is present in two of these loci. A rearrangement of 965 bp 3' to the ATG initiation codon generates two copies of pseudogenes where the C-terminal two-thirds of the alpha-subunit coding sequence is replaced with an unidentified coding frame. The other border of sequence divergence is located 733 bp upstream of the ATG initiation codon. Although multiple forms of alpha-subunit gene transcripts are present in mitochondria, the pseudogenes do not seem to express any alpha-subunit related polypeptide. PMID- 2886499 TI - A new endo-beta-galactosidase releasing Gal alpha 1----3Gal from carbohydrate moieties of glycoproteins and from a glycolipid. AB - Culture fluid of Clostridium perfringens contained an endoglycosidase releasing a galactosyl disaccharide from glycans derived from glycoproteins of teratocarcinoma OTT6050. The endoglycosidase was purified by ammonium sulfate precipitation, Sephadex G-200 column chromatography, and DEAE-Sephadex A-25 column chromatography. The structure of the disaccharide product was determined to be Gal alpha 1----3Gal. The enzyme also released the disaccharide from bovine thyroglobulin glycopeptide and from a pentaglycosyl ceramide (Gal alpha 1----3Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4Glc-Cer). Therefore, we concluded that the enzyme was an endo-beta-galactosidase cleaving Gal beta 1----4GlcNAc linkage. Keratan sulfate and the antigenic determinant of blood group type B were resistant to the enzyme: the specificity of the enzyme is different from other endo-beta-galactosidases so far described. The enzyme could act on intact thyroglobulin and defucosylated ovarian cyst mucin. PMID- 2886498 TI - Biochemistry and regulation of folate and methotrexate transport in Leishmania major. AB - Promastigotes of the protozoan parasite Leishmania major exhibit high affinity uptake of folate (Kt = 0.7 microM) and methotrexate (MTX) (Kt = 1.8 microM) which is saturable and sensitive to metabolic poisons. Influx of folate and MTX is competitively inhibited by 5-formyltetrahydrofolate and p-aminobenzoic acid glutamate, but not by 4-deoxy-4-amino-10-methylpteroate, biopterin, or pteroate. A single carrier is inferred for both folate and MTX transport, as the Ki of each inhibitor for both folate and MTX influx is the same, and the apparent affinities (Kt) of the substrates folate and MTX are identical to their respective Ki values for inhibition of MTX and folate uptake. Folate influx is specifically regulated according to cellular growth phase, as stationary phase cells exhibit 7% of the Vmax of log phase cells, while energy-dependent glucose uptake is only moderately reduced in stationary phase. Folate influx is also regulated by external folate levels, as cells grown in 5 microM folate exhibit 30% of the Vmax of cells grown in folate-depleted medium. Comparison of bacterial, mammalian, and Leishmania folate transport activities indicates considerable diversity in both biochemical and regulatory properties, and suggests the possibility that selective inhibition or manipulation of folate transport may be exploited in parasite chemotherapy. PMID- 2886500 TI - Dissociation of phosphate from beef heart mitochondrial F1-ATPase. Effect of adenine nucleotides. AB - The effect of exposure to adenine nucleotides on the dissociation of phosphate bound to beef heart mitochondrial F1-ATPase (F1) has been studied using a layered Sephadex centrifuge column method. The order of effectiveness of nucleotides in facilitating Pi dissociation from F1 was ATP greater than AMP-PNP much greater than ADP (where AMP-PNP indicates adenosine 5'-(beta,gamma-imido)triphosphate) when phosphate had bound to F1 as Pi from the medium. When ATP was present in amounts substoichiometric to F1, essentially all of the ATP present bound to F1, and the molar ratio of Pi released to ATP bound was near one. Under similar conditions AMP-PNP bound equally well to F1, but in order to effect similar amounts of Pi release it was necessary to use approximately 10 times as much AMP PNP as ATP. The order of effectiveness of nucleotides in facilitating dissociation of phosphate which had bound to F1 as the gamma-phosphate of ATP was ATP = AMP-PNP much greater than ADP. In this case ATP and AMP-PNP were as effective in facilitating phosphate dissociation as was ATP in the case in which phosphate had bound to F1 as Pi. It is concluded that when phosphate has bound to F1 as Pi, binding of one molecule of ATP or more than one molecule of AMP-PNP are sufficient to facilitate dissociation of phosphate. When phosphate has bound to F1 as the gamma-phosphate of ATP, binding of one molecule of either ATP or AMP PNP is sufficient to facilitate dissociation of phosphate. PMID- 2886501 TI - Amino acid and putative neurotransmitter transport in human Y79 retinoblastoma cells. Effect of insulin and insulin-like growth factor. AB - The binding of insulin and insulin-like growth factor I (IGF-I) and their effect on amino acid and neurotransmitter transport was studied in cultured human Y79 retinoblastoma cells. Y79 cells possess specific receptors for both insulin and IGF-I. Insulin binding to Y79 cells is characterized by a curvilinear Scatchard plot suggesting a two-site or two-affinity binding system. In contrast, IGF-I binding has a linear plot indicative of a one-site, one-affinity binding system. The uptake of glycine, a putative neurotransmitter in the retina occurs by a specific transport system in Y79 cells, independent of the uptake of other neutral amino acids. The uptake of glycine was increased 25-50% by either insulin or IGF-I. The response to insulin or IGF-I on glycine uptake is gradual and concentration dependent. The accumulation of other amino acids and putative retinal neurotransmitters by Y79 cells was not significantly affected by insulin of IGF-I. In addition, the activity of Na+/K+-ATPase was not influenced. The analysis of high affinity glycine uptake indicates that insulin and IGF-I are stimulating glycine transport by increasing the V'max without significantly affecting the K'm. Further analysis suggests that insulin and IGF-I are causing a recruitment of additional glycine transporters at the cell surface or activating otherwise nonfunctional transporters by an unexplained mechanism. Because of the implication that glycine responds as a neuroactive amino acid in Y79 cells these studies suggest that insulin and IGF-I may influence neuroactivity in the human retina by regulating the transport of glycine. PMID- 2886503 TI - Structural organization and DNA methylation patterning within the mouse L1 family. AB - We have studied stable differences in patterns of DNA methylation seen in the repeated sequences of mouse cells. A cloned 1330-base pair fragment of mouse repetitive DNA (pFS-13) was used as a probe in Southern blotting experiments. Mouse spleen and L1210 lymphoma DNA appeared to be normally methylated at HpaII sites probed by this sequence. Friend erythroleukemia cell, and Sp2 cell DNA both showed an abnormal banding pattern in HpaII digests. Hybridization in situ to metaphase chromosomes showed that probed sequences were broadly interspersed along the arms of each mouse chromosome. The DNA sequence of the 1330-base pair insert in the clone was determined; a copy of the R sequence of L1 was found at its 5' end. Walking experiments using M13 subclones from pFS-13 permitted the construction of a map for d(pCCGG) sites at the 3' end of the mouse L1 family. The unmethylated d(pCCGG) sites in Sp2 and Friend cells could then be assigned to polymorphic-repeated sequence groups within L1, homologous to the region spanned by BAM5 and R. Since there are several thousand copies of each of the fragments seen in autoradiographs, these sequences must possess a common methylation state at many genomic locations. Concerted (nonrandom) hypomethylation of certain subfamilies of L1 appears to be a stable characteristic of several cell lineages. These findings suggest that certain L1 families possess commonalities that permit and perhaps require differential DNA methylation in established cell lineages. PMID- 2886502 TI - Ammonia assimilation in Bacillus polymyxa. 15N NMR and enzymatic studies. AB - Pathways of ammonia assimilation into glutamic acid and alanine in Bacillus polymyxa were investigated by 15N NMR spectroscopy in combination with measurements of the specific activities of glutamate dehydrogenase, glutamine synthetase, glutamate synthetase, alanine dehydrogenase, and glutamic-alanine transaminase. Ammonia was found to be assimilated into glutamic acid predominantly by NADPH-dependent glutamate dehydrogenase with a Km of 2.9 mM for NH4+ not only in ammonia-grown cells but also in nitrate-grown and nitrogen fixing cells in which the intracellular NH4+ concentrations were 11.2, 1.04, and 1.5 mM, respectively. In ammonia-grown cells, the specific activity of alanine dehydrogenase was higher than that of glutamic-alanine transaminase, but the glutamate dehydrogenase/glutamic-alanine transaminase pathway was found to be the major pathway of 15NH4+ assimilation into [15N]alanine. The in vitro specific activities of glutamate dehydrogenase and glutamine synthetase, which represent the rates of synthesis of glutamic acid and glutamine, respectively, in the presence of enzyme-saturating concentrations of substrates and coenzymes are compared with the in vivo rates of biosynthesis of [15N]glutamic acid and [alpha,gamma-15N]glutamine observed by NMR, and implications of the results for factors limiting the rates of their biosynthesis in ammonia- and nitrate-grown cells are discussed. PMID- 2886504 TI - A comparison of the ability of various alpha-adrenoreceptor agonists to induce EGTA-resistant contractions of rat aorta. AB - Phenylephrine (PE) and Guanfacine (GU) produced maximum contractions of rat isolated aorta which were 96.8 +/- 1.3% and 96.0 +/- 2.8% respectively of the maximum responses induced by noradrenaline (NA). The responses produced by maximum concentrations of NA following 2 min incubation of the preparations with 3.0 mM EGTA were 38.1 +/- 1.2% of the maxima achieved in normal Krebs. PE produced maximum EGTA-resistant responses which were significantly less than those seen with NA; GU produced EGTA-resistant responses which were significantly less than those to PE. The concentration response curves to NA and PE were shifted to the right by incubation with EGTA. The curve for PE was shifted by a significantly greater degree than that for NA. Amidephrine, UK-14,304 and St-587 produced only nominal EGTA-resistant responses even though one of these (UK 14,304) produced contractions in normal Krebs which were almost 70% of the maximum achieved by NA. The log dose ratio for all agonists (except amidephrine) were similar following the addition of 5 nM prazosin. Amidephrine had no effect in the presence of this concentration of prazosin. It is concluded that all agonists tested were acting on alpha 1-adrenoreceptors. Prazosin (5 nM) but not corynanthine (2.5 microM) slowed the rate of rise of contraction of all agonists tested. It is proposed that the rate of rise of agonist/receptor combinations is an important determinant of alpha-adrenoreceptor agonist induced EGTA-resistant responses in rat aorta. PMID- 2886505 TI - Characterization of alpha-adrenoreceptor mediated reduction of flow in a saline perfused constant pressure model of rat perfused hindquarters. AB - An analysis of vasopressor responses elicited by alpha-adrenoreceptor agonists and KCl in a constant pressure saline perfused model of rat perfused hindquarters is presented. Using methoxamine (alpha 1), cirazoline (alpha 1), B-HT 920 (alpha 2) and St 587 (alpha 1) as alpha-adrenoreceptor agonists, and rauwolscine and prazosin as selective alpha 2- and alpha 1-adrenoreceptor antagonists, respectively, it is concluded that alpha-adrenoreceptor mediated vasoconstriction in this model is mediated by the alpha 1-subtype. Pretreatment of the animals with reserpine (i.p., at various doses and dose-regimens) or addition of angiotensin II (10(-9)-10(-6) M), PGF2 alpha(10(-8) & 5 X 10(-7) M) or KCl (2 & 4 X 10(-3) M), or changing [Mg2+] did not significantly affect the potency or intrinsic activity of the alpha-adrenoreceptor agonists studied. Experiments with the calcium entry blocking drugs gallopamil and nifedipine, or deletion of CaCl2 from the perfusion solution, did not reveal a contribution from the influx of extracellular calcium towards alpha 1-adrenoreceptor-mediated reduction of flow in RPH. KCl-induced vasoconstriction in RPH was found to be sensitive to the blockade of calcium entry by calcium entry blocking drugs, but not to alpha adrenoreceptor-blocking drugs and calmodulin antagonist. It is concluded that the model described here is of potential value in the characterization of alpha adrenoreceptor antagonists and calcium entry blocking drugs under in vitro conditions in resistance vessels of the rat. PMID- 2886506 TI - Do adrenaline-containing neurones from the rostral ventrolateral medulla excite preganglionic sympathetic cell bodies? AB - Experiments were performed to investigate whether descending vasomotor neurones from the rostral ventrolateral medulla (RVL) utilize adrenaline as a neurotransmitter. Electrical stimulation of the RVL caused marked, short lasting, reproducible increases in blood pressure and heart rate in anaesthetised atropine methylbromide-treated rats. These effects probably reflect activation of cell bodies rather than fibres of passage since injection of L-glutamate into the same area also produced tachycardia and vasopressor responses. The effects of RVL stimulation were unchanged after bilateral adrenalectomy but were markedly reduced by guanethidine (1 mg/kg, i.v.) suggesting that the tachycardia and vasopressor responses were mediated via increased sympathetic tone to the heart and vasculature. Pretreatment with the phenylethanolamine-N-methyl transferase (PNMT) inhibitor LY134046 (1 mg intracisternally, and 40 mg/kg i.p. daily for 1 day or 5 days) did not modify either the tachycardia or vasopressor response to stimulation of the RVL. Resting blood pressure and heart rate were also unchanged. Cardiac preganglionic sympathetic nerves supplying the heart arise from the C7-T2 region of the spinal cord. Phentolamine and propranolol were injected intrathecally (i.t.) in this region, in an attempt to block the spinal receptors at which any adrenaline, released locally during RVL stimulation, might be expected to act in order to elicit the characteristic tachycardia. Phentolamine (10 and 100 micrograms i.t.) and propranolol (1 microgram i.t.) did not modify the tachycardia but propranolol (10 and 100 micrograms i.t.) caused a dose-dependent reduction. These doses of propranolol (10 and 100 micrograms i.t.) also produced blockade of peripheral beta-adrenoreceptors. The failure of PNMT inhibition to modify the tachycardia or vasopressor response to RVL stimulation and the lack of effect of intrathecally injected alpha-and beta-adrenoreceptor antagonists (at doses which do not exert peripheral effects) against the RVL stimulation-induced tachycardia suggests that adrenaline does not subserve a spinal neurotransmitter role, at the C7-T2 region. PMID- 2886507 TI - Burns of the feet. AB - Although they are formally categorized by the ABA as major burns, isolated burns of the feet are often managed on an outpatient basis. This retrospective review evaluates the success of such outpatient management, including the complications encountered. The outcome of the review emphasizes that although isolated burns encompass only a small body surface area, they require careful in-hospital treatment to avoid the complications of cellulitis, subsequent prolonged hospitalization, increased need for skin grafting, and increased incidence of hypertrophic scarring. PMID- 2886508 TI - Female sterile (1) yolkless: a recessive female sterile mutation in Drosophila melanogaster with depressed numbers of coated pits and coated vesicles within the developing oocytes. AB - Ultrastructural analysis of developing oocytes produced by the recessive female sterile mutant, yolkless (yl), in Drosophila melanogaster shows that yl+ gene activity is necessary for coated pit and coated vesicle formation within these oocytes. 29 alleles of the mutation are known to exist, and they fall either within a strongly affected class or a weakly affected class. Analysis of oocytes produced by females homozygous for the strongly affected class of alleles shows a greater than 90% reduction in the numbers of coated pits and coated vesicles. These oocytes have very little proteinaceous yolk, and the females accumulate vitellogenin (the yolk protein precursor) within their hemolymph. Moreover, females homozygous or hemizygous for a given strong allele produce mature oocytes that are flaccid. Alternatively, females homozygous or hemizygous for weak alleles produce yolk-filled oocytes, but the number of coated pits and coated vesicles within these oocytes is 50% of that found in the oocytes of wild-type females. Despite the presence of yolk within these oocytes, females homozygous for weak yl- alleles remain sterile, and their mature oviposited eggs collapse with time. PMID- 2886509 TI - Postpolymerization detyrosination of alpha-tubulin: a mechanism for subcellular differentiation of microtubules. AB - Tyrosinated (Tyr) and detyrosinated (Glu) alpha-tubulin, species interconverted by posttranslational modification, are largely segregated in separate populations of microtubules in interphase cultured cells. We sought to understand how distinct Tyr and Glu microtubules are generated in vivo, by examining time dependent alterations in Tyr and Glu tubulin levels (by immunoblots probed with antibodies specific for each species) and distributions (by immunofluorescence) after microtubule regrowth and stabilization. When microtubules were allowed to regrow after complete depolymerization by microtubule antagonists, Glu microtubules reappeared with a delay of approximately 25 min after the complete array of Tyr microtubules had regrown. In these experiments, Tyr tubulin immunofluorescence first appeared as an aster of distinct microtubules, while Glu tubulin staining first appeared as a grainy pattern that was not altered by detergent extraction, suggesting that Glu microtubules were created by detyrosination of Tyr microtubules. Treatments with taxol, azide, or vinblastine, to stabilize polymeric tubulin, all resulted in time-dependent increases in polymeric Glu tubulin levels, further supporting the hypothesis of postpolymerization detyrosination. Analysis of monomer and polymer fractions during microtubule regrowth and in microtubule stabilization experiments were also consistent with postpolymerization detyrosination; in each case, Glu polymer levels increased in the absence of detectable Glu monomer. The low level of Glu monomer in untreated or nocodazole-treated cells (we estimate that Glu tubulin comprises less than 2% of the monomer pool) also suggested that Glu tubulin entering the monomer pool is efficiently retyrosinated. Taken together these results demonstrate that microtubules are polymerized from Tyr tubulin and are then rapidly converted to Glu microtubules. When Glu microtubules depolymerize, the resulting Glu monomer is retyrosinated. This cycle generates structurally, and perhaps functionally, distinct microtubules. PMID- 2886512 TI - Tolerance--a response to long-term treatment with beta 2-receptor stimulants. PMID- 2886511 TI - Proteoglycans and glycosaminoglycans induce gap junction synthesis and function in primary liver cultures. AB - Intercellular communication via gap junctions, as measured by dye and electrical coupling, disappears within 12 h in primary rat hepatocytes cultured in serum supplemented media or within 24 h in cells in a serum-free, hormonally defined medium (HDM) designed for hepatocytes. Glucagon and linoleic acid/BSA were the primary factors in the HDM responsible for the extended life span of the electrical coupling. After 24 h of culture, no hormone or growth factor tested could restore the expression of gap junctions. After 4-5 d of culture, the incidence of coupling was undetectable in a serum-supplemented medium and was only 4-5% in HDM alone. However, treatment with glycosaminoglycans or proteoglycans of 24-h cultures, having no detectable gap junction protein, resulted in synthesis of gap junction protein and of reexpression of electrical and dye coupling within 48 h. Most glycosaminoglycans were inactive (heparan sulfates, chondroitin-6 sulfates) or only weakly active (dermatan sulfates, chondroitin 4-sulfates, hyaluronates), the weakly active group increasing the incidence of coupling to 10-30% with the addition of 50-100 micrograms/ml of the factor. Treatment of the cells with 50-100 micrograms/ml of heparins derived from lung or intestine resulted in cells with intermediate levels of coupling (30 50%). By contrast, 10-20 micrograms/ml of chondroitin sulfate proteoglycan, dermatan sulfate proteoglycan, or liver-derived heparin resulted in dye coupling in 80-100% of the cells, with numerous cells showing dye spread from a single injected cell. Sulfated polysaccharides of glucose (dextran sulfates) or of galactose (carrageenans) were inactive or only weakly active except for lambda carrageenan, which induced up to 70% coupling (albeit no multiple coupling in the cultures). The abundance of mRNA (Northern blots) encoding gap junction protein and the amounts of the 27-kD gap junction polypeptide (Western blots) correlated with the degree of electrical and dye coupling indicating that the active glycosaminoglycans and proteoglycans are inducing synthesis and expression of gap junctions. Thus, proteoglycans and glycosaminoglycans, especially those found in abundance in the extracellular matrix of liver cells, are important in the regulation of expression of gap junctions and, thereby, in the regulation of intercellular communication in the liver. The relative potencies of heparins from different tissue sources at inducing gap junction expression are suggestive of functional tissue specificity for these glycosaminoglycans. PMID- 2886513 TI - Determination of a new benzamide, amisulpride, in human plasma by reversed-phase ion-pair high-performance liquid chromatography. PMID- 2886510 TI - Sequential phosphorylation of chartin microtubule-associated proteins is regulated by the presence of microtubules. AB - Chartins are a unique class of three families of microtubule-associated proteins, each consisting of several isoforms possessing varying degrees of phosphorylation. The most highly phosphorylated chartin isoforms are highly enriched in neuronal cell fractions containing microtubules and there is evidence that their phosphorylation may play a role in promoting neurite outgrowth. The present work describes the relationship between the phosphorylation state of chartins and the presence of intact microtubules in long-term cultures of NGF treated, neurite-bearing PC12 cells. Cultures were depleted of microtubules by exposure to high concentrations of depolymerizing agents for 2-24 h. Radiolabeling of cellular proteins with [32P]orthophosphate or [35S]methionine revealed that both the ongoing and steady-state phosphorylation of chartins is markedly altered under these conditions. Two-dimensional isoelectric focusing by SDS-PAGE of whole cell extracts demonstrated that the more acidic, highly phosphorylated isoforms are diminished with a concomitant increase in the more basic, less phosphorylated isoforms. These phosphorylation changes were relatively specific for the chartins and were not observed for phosphorylated MAP 1.2, phospho-beta-tubulin, or most other phosphoproteins. Thus, the phosphorylation state of chartins, but not of other phosphoproteins, is regulated by the presence of native microtubules. Despite depolymerization of microtubules, neurites remained extended for at least 24 h. Neurite elongation, however, was arrested. Microtubules, therefore, may be required for extension, but not for short-term maintenance of well-established neurites. Taxol, which promotes tubule assembly and stability, does not, conversely, drive phosphorylation of the chartins. Instead, taxol appeared to decrease the turnover of phosphate in microtubule-associated, acidic chartin isoforms. These data suggest several models as to how chartin phosphorylation is regulated in neurite-bearing cells and indicate that phosphorylation of cytoplasmic and microtubule-associated chartins occurs via different mechanisms. PMID- 2886514 TI - Plasmid analysis as a means of strain differentiation in Clostridium perfringens. AB - A total of 114 Clostridium perfringens isolates were serotyped and examined for plasmids. Fifty-two strains were from hospitalized patients with diarrhea or from hospital environments, and 62 epidemiologically unrelated isolates were obtained from food poisoning outbreaks. All strains were screened for bacteriocin production against a common indicator strain of C. perfringens. In the one significant hospital outbreak of C. perfringens diarrhea, three to five plasmid types were found in strains of the predominant serotype, but no similar correlation between serotype and plasmid type was found in random isolates from a variety of sources. All of the strains associated with the diarrhea outbreak produced bacteriocins, whereas 63% of the strains from various sources produced bacteriocins. The typing data suggest a promising differentiating capability for plasmid analysis in the epidemiological study of outbreaks of food poisoning, diarrhea, or infections caused by C. perfringens. PMID- 2886517 TI - Hepatitis in vervet monkeys caused by Fusarium moniliforme. AB - The fungus Fusarium moniliforme Sheldon is a common contaminant of maize (Zea mays L.) intended for human and animal consumption throughout the world. Culture material of F. moniliforme MRC 826, isolated from home-grown maize in an area in Transkei, southern Africa, with a high rate of human oesophageal cancer, was highly toxic to vervet monkeys (Cercopithecus pygerythrus). Ten monkeys were fed a standard primate diet which contained various amounts of culture material for 180 days. Two control monkeys received the standard diet without culture material. Pathological changes observed in liver biopsies taken by laparotomy were characterized by focal disturbance of the trabecular structure, degeneration and necrosis of hepatocytes, mononuclear infiltration, and in severe cases by cirrhosis. Biochemical changes, particularly increases in liver enzyme activities in serum, paralleled the liver damage seen by light microscopy. The acute, subacute and chronic toxic hepatitis induced in various degrees in all the monkeys fed fungal culture material showed close similarity with human viral hepatitis. The lesions also have some similarities to those induced in primates by aflatoxin, but differ in several respects. Ultrastructural nuclear and nucleolar changes caused by F. moniliforme, i.e. marginal clumping of chromatin and large nucleoli with segregation of fibrillar and granular components, suggested some similarity with the changes reported to be caused by aflatoxin and some other hepatocarcinogens. A long-term feeding experiment in vervet monkeys with F. moniliforme MRC 826 and attempts to isolate and chemically characterise the hepatotoxic metabolite(s) produced by this fungus are being continued. PMID- 2886516 TI - Somatostatin immunoreactive neurons in the human hippocampus and cortex shown by immunogold/silver intensification on vibratome sections: coexistence with neuropeptide Y neurons, and effects in Alzheimer-type dementia. AB - The distribution of somatostatinlike immunoreactivity was studied in the hippocampal formation, retrohippocampal region, and temporal cortex in the human brain. Tissues from surgical biopsy and postmortem cases were used, and the immunogold/silver method on vibratome sections was introduced for routine applications in conjunction with primary antisera that recognise somatostatin-14 or somatostatin-28. Somatostatin-28 antisera readily stained numerous neurons, dendrites, and extensive axonal networks throughout the hippocampus and neighbouring cortex. Liquid phase absorption provided controls for specificity. The most prominent accumulations of somatostatin immunoreactive neurons and axons occurred in the hilus of the area dentata, in CA1, and in the entorhinal and perirhinal cortices. Axonal plexuses occurred throughout the hippocampal subfields but were particularly dense in those regions rich in somatostatin neurons. The distribution of somatostatin immunoreactive neurons and fibers parallels the distribution of neuropeptide Y (NPY) neurons and fibers in the hippocampus and cerebral cortex to a remarkable extent. Double labelling experiments with antisera against neuropeptide Y and somatostatin indicate a considerable frequency of coexistence of the two peptides in single neurons, particularly in large multipolar cortical neurons and also in the small bipolar white matter neurons. Regional variations exist in the amounts of coexistence found in the hippocampal subfields; somatostatin-NPY coexistence is particularly high in the hilus of the area dentata, the subicular complex, and the deep layers of the entorhinal and perirhinal cortices. In the hippocampi and temporal cortices in cases of Alzheimer-type dementia compared to those of age-matched control brains, there is a significant to severe loss of somatostatin immunoreactive neurons and axons. This loss is most severe in those regions with the highest indices of neurofibrillary tangles and neuritic plaques-the hilus of the area dentata, CA1, and the entorhinal and perirhinal cortices. Surviving somatostatin neurons are distorted with short dendrites and truncated axons. Neuritic plaques identified on double label experiments with thioflavin include somatostatin axons but not neurons. PMID- 2886515 TI - Early posthypoglycemic insulin resistance in man is mainly an effect of beta adrenergic stimulation. AB - The insulin effect following hypoglycemia was studied with the euglycemic clamp technique in seven healthy subjects. Following an initial euglycemic clamp hypoglycemia was induced and after glucose recovery a second clamp was performed. Glucose production (Ra) and utilization (Rd) were studied with [3-3H]glucose. Each subject was studied four times; during infusion of placebo, propranolol, somatostatin, and a control study where hypoglycemia was prevented. Hypoglycemia induced an insulin resistance with a lower steady state glucose infusion rate following the hypoglycemia during placebo as compared to the control study (2.5 +/- 0.5 and 4.8 +/- 1.0 mg/kg min, respectively, P less than 0.05). The insulin resistance was due to an attenuated insulin effect on both inhibition of Ra (impaired by 37%) and stimulation of Rd (impaired by 61%). The insulin antagonistic effect was completely prevented by propranolol but only partly by somatostatin. Thus, early posthypoglycemic insulin resistance (2.5-3.5 h after hypoglycemia) is a sustained effect mainly due to beta-adrenergic stimulation. PMID- 2886518 TI - Serum enzyme changes in calves experimentally infected with Schistosoma bovis. AB - The activities of the enzymes SD, GD, AAT, 5'NT, GGT, LDH and CPK were determined weekly in sera of two calves each infected with 10,000 S. bovis cercariae and in two controls. In infected animals, LDH activity increased from the first week of exposure and remained high throughout the experiment (22 weeks). GGT activity increased nine weeks after exposure and remained high. CPK activity was elevated during weeks 8-15 of infection. No change was detected in the activity of the other enzymes, nor in any enzymes of the controls. PMID- 2886520 TI - Altered sympathetic-salivary gland development: delayed response to postnatal castration. AB - These studies defined the normal and hormonally altered development of activity for tyrosine hydroxylase (T-OH), the rate-limiting enzyme in catecholamine biosynthesis (Levitt et al., 1965), and choline acetyltransferase activity (CAT) in the male rat superior cervical ganglion (SCG). Additionally, salivary gland weight was monitored. Two distinct developmental plateaus for postsynaptic T-OH activity exist. The first plateau represents the prepubertal level, which is significantly lower than the second postpubertal plateau. In contrast, presynaptic CAT activity displayed only a single plateau, commencing at approximately 45 days of age. The effects of postnatal castration (at 10 or 11 days of age) on the submandibular gland and T-OH activity were delayed until after puberty. No change in T-OH activity was seen at two and four post-operative weeks between control and castrated animals; however, T-OH activity was significantly less in castrated animals at 12 and 16 post-operative weeks. Testosterone replacement reversed the effect of castration on T-OH activity. Conversely, CAT activity in the SCG was unchanged by postnatal castration for at least 16 post-operative weeks, the longest time point studied. The failure of castrated animals to display the normal developmental increase in T-OH activity following puberty was comparable with the effect of castration on the development of submandibular salivary gland weight. These results suggest that in postpubertal male rats, development of T-OH activity in the superior cervical ganglion is influenced by testosterone. The parallel effects of castration on submandibular gland weight imply that testosterone regulates T-OH activity via an indirect mechanism. In contrast to noradrenergic enzyme activity and target tissue size, the ontogeny of presynaptic CAT activity appears to be insensitive to testosterone levels. PMID- 2886519 TI - Recurrent eruptions following unusual solitary coelenterate envenomations. AB - The case history of four patients is presented. The first patient exhibited normal immunologic reactions to large artificial intradermal challenge with jellyfish venom and later, multiple small natural stings. The second patient, presumably envenomated by a jellyfish, had four recurrent cutaneous eruptions in a linear configuration at the same anatomic site. Because her primary coelenterate contact occurred at a time when she was receiving systemic corticosteroids, it is assumed that the eruption due to the initial sting was delayed. The third and fourth patients exhibited recurrent eruptions after solitary envenomations by different coelenterates. These case histories demonstrate that multiple recurrent eruptions may follow solitary envenomations by different subphyla of coelenterates, that the initial eruption induced by the sting may be delayed by the administration of high doses of systemic corticosteroids, and that an immunologic reaction in both the B and T cell systems can follow jellyfish envenomation. PMID- 2886521 TI - Studies of blood histamine levels during topical corticosteroid therapy compared with those during systemically administered corticosteroids. PMID- 2886522 TI - Dystonia: therapy with high dosage anticholinergic medication. PMID- 2886523 TI - Control of infection on the two sides of the Atlantic. PMID- 2886524 TI - Molecular methods for the investigation of bacterial cross-infection. PMID- 2886525 TI - The national prevalence survey of nosocomial infections in Belgium, 1984. AB - A national one-day prevalence survey of nosocomial infections was carried out in March 1984 in 106 Belgian acute-care hospitals involving 8723 patients of whom 6130 had undergone surgery. Three infections were studied: surgical wound infection, bacteraemia and urinary-tract infection. One or more of these three infections was recorded in 9.3% of all patients and in 11.8% of surgical patients. Prevalences increased with increasing duration of hospital stay and with higher ages, but the association of HAI with age was no longer significant after correction for duration of hospital stay. Prevalences varied considerably in different specialties. After adjustment for age and duration of stay, there was no association between perioperative antibiotic prophylaxis and the prevalence of the infections studied, but bias due to selection of higher risk patients in the antibiotic group was probable. Larger hospitals had a higher overall prevalence, but populations differed according to the size of the hospital. Bacteraemia was strongly associated with the presence of an intravenous catheter, and urinary-tract infection with a urinary catheter. PMID- 2886526 TI - The effect of introducing a policy for catheter care on the catheter infection rate in a small hospital. AB - The mean urinary infection rate of patients with indwelling urinary catheters in an 250-bed hospital was reduced using a specifically designed catheter care policy. However, the influence of several uncontrolled factors could not be assessed. PMID- 2886528 TI - Blood transfusion-associated Pseudomonas fluorescens septicaemia: is this an increasing problem? AB - Pseudomonas fluorescens transfusion-related septicaemia (TRS) is rare. We present the first description in the UK of two cases of TRS caused by this organism. PMID- 2886527 TI - A survey, in Scotland, of measures to prevent infection following orthopaedic surgery. AB - The current use of methods, in Scotland, to prevent infection following orthopaedic surgery was established by postal questionnaire. Thirty-five per cent of surgeons used antibiotic cement routinely for total hip replacement. Ultraclean air facilities were provided for only 19%. Ninety-one per cent of surgeons used prophylactic parenteral antibiotics during total hip replacement, 75% in the management of open fractures, but only 12% for metal implants. Most chose an appropriate antibiotic. Only one-third of surgeons used an antibiotic regimen of appropriate duration and timing for total hip replacement or when employing metal implants. PMID- 2886530 TI - Comparative susceptibility of hospital isolates of gram-negative bacteria to antiseptics and disinfectants. AB - The sensitivity of hospital isolates of Gram-negative bacteria to cationic antiseptics, mercuric chloride and two organomercury compounds has been measured. A comparison was made with laboratory strains of known sensitivity which acted as standards. All strains of Escherichia coli showed a uniformly high sensitivity to chlorhexidine diacetate; other organisms tended to be less sensitive to the biguanide. Quaternary ammonium compounds were less effective than chlorhexidine. Resistance to mercuric chloride was observed frequently, but there was little evidence of organomercurial resistance except in Pseudomonas aeruginosa isolates. PMID- 2886529 TI - A comparison of single-dose and multi-dose metronidazole prophylaxis for hysterectomy. AB - A multi-centre double-blind, placebo-controlled clinical trial was performed to determine the minimum number of doses of metronidazole required for effective prophylaxis of vaginal cuff abscess following hysterectomy. Four hundred and seventy-five patients received zero, one, two, three, six or twenty-one 500 mg doses of metronidazole. Data from 440 patients were analysed and showed that one dose of metronidazole markedly reduced the risk of vaginal cuff abscess in patients undergoing vaginal hysterectomy. The effect on vaginal cuff cellulitis was not evident. It is concluded that one preoperative dose of 500 mg metronidazole is an effective, convenient and cheap prophylaxis for patients undergoing vaginal hysterectomy. PMID- 2886531 TI - Carbon dioxide laser irradiation of bacterial targets in vitro. AB - Agar targets seeded with Escherichia coli and Staphylococcus aureus in roll tubes simulating the vaginal vault were irradiated with a CO2 laser at various power densities and durations. Viable bacteria were detected in the plume emissions in all instances. Staphylococcus aureus was found to be more resistant to the thermal effects of lasing than E. coli. This suggests that CO2 irradiation of cervical lesions could disseminate viable particles which may be a hazard for patients and operators. PMID- 2886532 TI - Post-transplant peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. AB - Two patients previously managed by continuous ambulatory peritoneal dialysis for end stage renal failure received cadaveric renal transplants. The peritoneal catheter was capped off and left in situ postoperatively. Both patients developed bacterial peritonitis shortly after transplantation. It was felt that the infections were associated with the presence of the indwelling peritoneal catheter as there was no clinical evidence of peritonitis at the time of transplantation. PMID- 2886533 TI - Empirical treatment of febrile, neutropenic patients with tobramycin and latamoxef. AB - One hundred and two febrile episodes in neutropenic patients were treated with intravenous tobramycin and latamoxef. After 48 h latamoxef at 6 g day-1, patients were randomized to continue this regimen or latamoxef at 3 g day-1. Infections responded to these regimens in 67% and 71% of patients, respectively. Two-thirds of the infections which failed to respond were due to coagulase-negative staphylococci in Hickman catheters, a trend which may necessitate the inclusion of additional antibiotics in future empirical regimens. Prolonged prothrombin times due to antibiotic therapy were seen in nine patients but there was only one episode of bleeding and this responded quickly to treatment with vitamin K and fresh frozen plasma. In 35 patients, coagulopathy was present before antibiotics were started, and these cases also responded to vitamin K. The study shows that the response to tobramycin and latamoxef is comparable to other broad-spectrum antibiotic regimens and that a reduction in the dose of latamoxef after 48 h treatment may safely permit cost savings. PMID- 2886534 TI - Single dose mezlocillin versus three dose cefuroxime plus metronidazole for the prophylaxis of wound infection after large bowel surgery. AB - A prospective, randomized, controlled trial was conducted in 116 consecutive patients undergoing colorectal surgery to compare single dose prophylaxis with mezlocillin to cefuroxime plus metronidazole in three doses. Patients were randomized to receive either a single dose of iv mezlocillin (5.0 g) or three doses of iv cefuroxime plus metronidazole at 8-hourly intervals. The first dose was given on the operating table. The overall wound infection rate in the mezlocillin treated patients (n = 54) was 30% and in the patients treated with cefuroxime plus metronidazole (n = 56) 25%. This difference is not statistically significant. When trivial wound infections were disregarded the wound infection rates were 11% and 16% respectively, which again was not statistically significant. PMID- 2886536 TI - Evaluation of dishwashing machines in four hospitals. AB - Fifteen dishwashing machines tested in four different hospitals failed to satisfy the minimum heat treatment requirement of 82 degrees C for 2 min for satisfactory thermal disinfection. The causes of failure included design faults in the machines with lack of time temperature controls, hard water supply, inadequately treated water, improper softening and inadequate preventative maintenance. PMID- 2886535 TI - An outbreak of Serratia marcescens infection following urodynamic studies. AB - Serratia marcescens was isolated from the urine of five patients, two of whom subsequently developed septicaemia with other Gram-negative bacilli. Four of the five patients had undergone urodynamic investigation. An inadequately sterilized re-usable rectal balloon was identified as the source of infection. PMID- 2886537 TI - The structure and functions of a district food hygiene group. PMID- 2886538 TI - Outbreaks of viral gastroenteritis caused by small round structured virus in psycho-geriatric patients. PMID- 2886539 TI - Decontamination and air-conditioning. PMID- 2886540 TI - A search for endogenous Na+,K+-ATPase inhibitor in acutely volume-expanded hog plasma led to lysophosphatidylcholine gamma-stearoyl. AB - An Na+,K+-ATPase inhibitor possessing inhibitory activity against the specific binding of ouabain to Na+,K+-ATPase has been purified from the plasma of acutely saline-infused hogs. The purification was performed by a combination of Amberlite XAD-2 adsorption chromatography and five steps of high-pressure liquid chromatography (HPLC). Fast atom bombardment mass and proton nuclear magnetic resonance (NMR) spectrometric studies identified the purified substance as lysophosphatidylcholine gamma-stearoyl (LPCS). The ouabain-displacing activity in plasma, due to this compound, increased with time during saline infusion. The maximal level reached was approximately 12 times higher than that in the pre infusion plasma sample. Lysophosphatidylcholines (LPCs) containing myristoyl, palmitoyl and oleoyl groups were also inhibitory to Na+,K+-ATPase and ouabain binding to the enzyme. These LPCs were effective at 100 mumol/l concentrations in attaining 50% inhibition of the enzyme activity and ouabain-binding activity of Na+,K+-ATPase. These results suggest that LPCs containing long chain fatty acids could play an important role as a Na+,K+-ATPase inhibitors under volume-expanded conditions. PMID- 2886541 TI - Dopamine produces forearm vasodilatation following alpha-adrenoceptor blockade by an action on vascular dopamine (DA1) receptors in man. AB - The purpose of this study was to investigate the receptor type mediating dopamine induced forearm vasodilatation following alpha-adrenoceptor blockade. Forearm blood flow (FBF) was measured using venous occlusion plethysmography in normal volunteers. Intra-arterial (i.a.) dopamine alone produced variable and small changes in FBF. However, following alpha-adrenoceptor blockade with phenoxybenzamine, dopamine infusion resulted in forearm vasodilatation in the infused arm. This effect was not antagonized by the beta-adrenoceptor antagonist propranolol, but was antagonized by the vascular dopamine receptor antagonist, sulpiride, the (d) enantiomer being more active than the (l). It is concluded that i.a. dopamine induces forearm vasodilatation following alpha-adrenoceptor blockade by an action on vascular dopamine (DA1) receptors similar to those described in the renal and mesenteric vasculature of other species. PMID- 2886543 TI - Host age as a determinant of infection rates with the mosquito pathogen Lagenidium giganteum (Oomycetes: Lagenidiales). PMID- 2886542 TI - Isotype switching in human B lymphocyte malignancies occurs by DNA deletion: evidence for nonspecific switch recombination. AB - The mechanism and specificity of isotype switching operative in human B lymphocytes was investigated by a determination of immunophenotype and immunoglobulin heavy and light chain gene status in a panel of human Ig-, IgM, IgG, and IgA B cell malignancies. Regardless of specific tumor type or switched immunophenotype, isotype switching was accompanied by the rearrangement of the expressed CH gene downstream of VDJH, with concomitant deletion of upstream CH genes in all cases. On the allelically excluded chromosome, 25% of the IgG or IgA tumors have retained C mu, and 75% have deleted C mu. The 5' recombination breakpoints for both productive and excluded alleles lie within or near S mu, 3' of the enhancer. No correlation between the extent of allelically excluded CH deletions and the isotype produced by the tumor was observed. Excluded chromosome deletion endpoints were found 5', equal to, or 3' of productive chromosome deletion endpoints. Furthermore, we have identified at least one IgM+ tumor that has undergone abortive CH gene deletions and have observed several unanticipated switch region deletions and potential translocations. The data suggest that isotype switching in human B cells occurs by a nonsubclass- and nonclass-specific switch recombinase. PMID- 2886545 TI - Geriatric aspects of psychopharmacology. Part B. PMID- 2886544 TI - [Ultracytochemical localization of adenylate cyclase and guanylate cyclase activities in human term placenta]. AB - Reports have so far accumulated suggesting that cyclic nucleotide may play an important role in the regulation of placental function, including fetal growth. However, only biochemical data are available on the localization of adenylate cyclase (AC) and guanylate cyclase (GC) and direct histochemical evidence is lacking. Therefore, to understand the cyclic nucleotide metabolism in human term placenta, ultracytochemical localization of AC and GC activity was studied. The AC activity was mainly positive on the basal plasma membrane of syncytiotrophoblast and on the pinocytotic vesicle of fetal capillary endothelial cell. GC activity was observed to be strong on the plasma membrane of microvilli of syncytiotrophoblast. All the cytochemical control studies confirmed the specificities of each enzyme activity. These observations suggest that syncytiotrophoblast may play an important role in cyclic nucleotide metabolism and that AC may receive information from fetal circulation, whereas GC may receive regulation from maternal circulation. PMID- 2886546 TI - Genetic controls over melanocyte differentiation: interaction of agouti-locus and albino-locus genetic defects. AB - Tyrosinase activities and dopachrome conversion activity were evaluated in extracts made from skins of 6-day-old mice that were mutant at the agouti and albino loci. Dopa oxidase (DO) activity of tyrosinase in fully pigmented (C/C) mice is reduced in extracts made from skins of yellow 6-day-old mice as compared to those of black mice. Dopachrome conversion (DC) activity is absent from skin extracts of normal yellow mice and is present in normal black mice. DC activity is a characteristic of a separate enzyme which has been called dopachrome conversion factor or dopachrome oxidoreductase. We measured the dopa oxidase activity and dopachrome conversion activity in skin extracts of yellow mice and black mice that were mutant at the albino (C) locus. Extracts made from extreme dilution (ce/ce) mice do not have DO activity. Those from yellow extreme-dilution mice do not have DC activity, while those from black, extreme-dilution mice do. The DO and DC activities that characterize skin extracts made from platinum (cp/cp) yellow mice are similar to those of platinum black mice. These observations suggest possible mechanisms by which the functions controlled by the agouti and albino loci interact to control melanogenesis. PMID- 2886547 TI - The physician assistant as forensic investigator. AB - Physician assistants are employed as forensic investigators at the Office of the Medical Examiner, Suffolk County, New York. We describe the educational qualifications of physician assistants and their valuable role in forensic medicine in Suffolk County. PMID- 2886548 TI - Nucleotide sequence of the genome region encoding the 26S mRNA of eastern equine encephalomyelitis virus and the deduced amino acid sequence of the viral structural proteins. AB - The 26S mRNA and most of the nsP4 encoding regions of the eastern equine encephalomyelitis (EEE) viral genome have been cloned. Excluding the poly(A) tail, the 26S mRNA region was determined to be 4139 nucleotides long and to share the same general organization as that of other alphaviruses. A highly conserved region of 19 nucleotides, the putative transcriptase recognition site for 26S mRNA synthesis, was present at the 26S/42S junction region of the 42S genomic RNA. Translation of the 26S mRNA began at the first AUG (positions 59 to 61) initiation codon and continued with an open reading frame that coded for a polyprotein of 1258 amino acids ending at a UAA ochre termination codon (positions 3776 to 3778). All four putative posttranslational cleavage sites used to generate the capsid, E3, E2, 6K and E1 proteins were conserved. Transmembrane domains present in the EEE virus structural polyprotein have been identified and their functions discussed. Pairwise comparison of the deduced amino acid sequences of the polyproteins of five alphaviruses (EEE, Venezuelan equine encephalitis, Sindbis, Semliki Forest and Ross River viruses) revealed EEE virus to be more closely related to VEE virus than to the other three viruses. PMID- 2886549 TI - Small animals are not susceptible to human immunodeficiency virus infection. AB - Several species of small animals were inoculated at birth or as adults with blood components from patients with acquired immunodeficiency syndrome (AIDS) and AIDS related disorders, or with the human immunodeficiency virus (HIV). No ill effects were noted in rats, hamsters, guinea-pigs, rabbits or musk shrews. Mice inoculated with clinical specimens had a significant incidence of mortality as compared with control groups (18.7% against 5.9%, P less than 0.025). Mice receiving HIV showed an increase in mortality, but it was not statistically significant. Infection of the animals by HIV could not be detected by virological or immunological studies. We concluded that none of these animal species provided a useful model for evaluating HIV infection. PMID- 2886550 TI - Inhibition of tyrosine hydroxylase activity by serotonin in explants of newborn rat locus ceruleus. AB - The long-term regulation of tyrosine hydroxylase (TH) by serotonin has been studied with cultures of newborn rat locus ceruleus explants. The presence of serotonin in the culture medium for a 24-h period was followed by an inhibition of TH activity in the explants. This effect lasted several days, with a maximal effect 2 days after treatment. Moreover, the decrease was reversible and dependent on the concentration of serotonin used (from 1 microM to 1 mM). The mechanisms of this regulation have been studied using drugs such as those known to act specifically on serotoninergic receptors and those known to interfere with protein synthesis. Thus, the action of serotonin (10(-5) M) on TH activity was suppressed with equimolar concentrations of serotoninergic antagonists such as metergoline or methiothepin. It was reproduced by quipazine, a drug capable of acting as a serotoninergic agonist. Inhibitors of protein synthesis acting either at the transcriptional or the translational levels can reproduce the inhibition of TH activity by serotonin alone. Furthermore, the effects of one or the other of these compounds and that of serotonin were not additive. This study confirms the hypothesis of an inhibitory control by serotonin on TH activity in the noradrenergic neurons of the locus ceruleus. Serotonin could regulate the synthesis of the enzyme through specific serotoninergic receptors. PMID- 2886551 TI - Amino acid changes in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy. AB - Brain tissue was obtained at autopsy from nine cirrhotic patients dying in hepatic coma and from an equal number of controls, free from neurological, psychiatric, or hepatic diseases, matched for age and time interval from death to freezing of dissected brain samples. Glutamine, glutamate, aspartate, and gamma aminobutyric acid (GABA) levels were measured in homogenates of cerebral cortex (prefrontal and frontal), caudate nuclei, hypothalamus, cerebellum (cortex and vermis), and medulla oblongata as their o-phthalaldehyde derivatives by HPLC using fluorescence detection. Glutamine concentrations were found to be elevated two- to fourfold in all brain structures, the largest increases being observed in prefrontal cortex and medulla oblongata. Glutamate levels were selectively decreased in prefrontal cortex (by 20%), caudate nuclei (by 27%), and cerebellar vermis (by 17%) from cirrhotic patients. On the other hand, GABA content of autopsied brain tissue from these patients was found to be within normal limits in all brain structures. It is suggested that such region-selective reductions of glutamate may reflect loss of the amino acid from the releasable (neurotransmitter) pool. These findings may be of significance in the pathogenesis of hepatic encephalopathy resulting from chronic liver disease. PMID- 2886552 TI - Occurrence and sequence complexity of polyadenylated RNA in squid axoplasm. AB - Axoplasmic RNA from the giant axon of the squid (Loligo pealii) comprises polyadenylated [poly (A)+] RNA, as judged, in part, by hybridization to [3H]polyuridine and by in situ hybridization analyses using the same probe. The polyadenylate content of axoplasm (0.24 ng/microgram of total RNA) suggests that the poly(A)+ RNA population makes up approximately 0.4% of total axoplasmic RNA. Axoplasmic poly(A)+ RNA can serve as a template for the synthesis of cDNA using a reverse transcriptase and oligo(deoxythymidine) as primer. The size of the cDNA synthesized is heterogeneous, with most fragments greater than 450 nucleotides. The hybridization of axoplasmic cDNA to its template RNA reveals two major kinetic classes: a rapidly hybridizing component (abundant sequences) and a slower-reacting component (moderately abundant and rare sequences). The latter component accounts for approximately 56% of the total cDNA mass. The rapidly and slowly hybridizing kinetic components have a sequence complexity of approximately 2.7 kilobases and 3.1 X 10(2) kilobases, respectively. The diversity of the abundant and rare RNA classes is sufficient to code for one to two and 205, respectively, different poly(A)+ RNAs averaging 1,500 nucleotides in length. Overall, the sequence complexity of axoplasmic poly(A)+ RNA represents approximately 0.4% that of poly(A)+ mRNA of the optic lobe, a complex neural tissue used as a standard. Taken together, these findings indicate that the squid giant axon contains a heterogeneous population of poly(A)+ RNAs. PMID- 2886553 TI - Significance of testosterone in regulating hypothalamic content and in vitro release of beta-endorphin and dynorphin. AB - The effects of castration and testosterone replacement on hypothalamic pools of beta-endorphin and dynorphin and on the basal and corticotropin-releasing factor (CRF)-stimulated release of these peptides from hypothalamic slices in vitro were studied. The experiments were done in adult male rats. The hypothalamic content of both peptides increased significantly within 1 week of castration, and levels remained elevated for up to 4 weeks. Testosterone treatment, begun at the time of castration, prevented these increases. In addition, testosterone replacement 6 weeks after castration reversed peptide levels to normal. Basal in vitro release rates of beta-endorphin and dynorphin were significantly lower from hypothalamic slices derived from 1-week castrated animals than from intact males, and when testosterone was administered in various doses in vivo, basal release rates in vitro increased in a dose-related manner. Hypothalami from rats that had been castrated for 4 weeks, however, showed basal release rates similar to those in tissues from intact controls, a finding indicating that castration initially alters both opioid peptide synthesis and release; later, release is normalized, whereas synthesis remains elevated. CRF was found to stimulate beta-endorphin and dynorphin release from hypothalami from intact and from 1- and 4-week-castrated rats, a result indicating that castration does not alter the response of beta endorphin and dynorphin neurons to this stimulus. PMID- 2886554 TI - Further characterization of dopamine release by permeabilized PC12 cells. AB - Rat pheochromocytoma cells (PC12) permeabilized with staphylococcal alpha-toxin release [3H]dopamine after addition of micromolar Ca2+. This does not require additional Mg2+-ATP (in contrast to bovine adrenal medullary chromaffin cells). We also observed Ca2+-dependent [3H]-dopamine release from digitonin permeabilized PC12 cells. Permeabilization with alpha-toxin or digitonin and stimulation of the cells were done consecutively to wash out endogenous Mg2+-ATP. During permeabilization, ATP was removed effectively from the cytoplasm by both agents but the cells released [3H]dopamine in response to micromolar Ca2+ alone. Replacement by chloride of glutamate, which could sustain mitochondrial ATP production in permeabilized cells, does not significantly alter catecholamine release induced by Ca2+. However, Mg2+ without ATP augments the Ca2+-induced release. The release was unaltered by thiol-, hydroxyl-, or calmodulin interfering substances. Thus Mg2+-ATP, calmodulin, or proteins containing -SH or OH groups are not necessary for exocytosis in permeabilized PC12 cells. PMID- 2886555 TI - Synergistic action of postsynaptic alpha-adrenergic receptor stimulation on vasoactive intestinal polypeptide-induced increases in pineal N-acetyltransferase activity. AB - The alpha-adrenergic agonists phenylephrine and methoxamine, at concentrations that have little effect on pineal N-acetyltransferase activity, markedly enhance stimulation of this enzyme by vasoactive intestinal polypeptide (VIP). This augmentation can be blocked by the alpha 1-adrenergic antagonists phenoxybenzamine and prazosin and, at 10 but not 1 microM, by the alpha 2 antagonist yohimbine. The time course for VIP stimulation is not altered by concomitant alpha-adrenergic stimulation. Augmented activity does not require concomitant alpha-adrenergic stimulation, but alpha-adrenergic agonists must be present for augmentation to be maintained. Phorbol 12,13-diacetate or -dibutyrate but not 4 alpha-phorbol can substitute for phenylephrine, a finding suggesting that protein kinase C is involved in the augmentation. These results are, in general, analogous to alpha-adrenergic magnification of N-acetyltransferase induction by beta-adrenergic agonists. PMID- 2886556 TI - Blood-brain barrier monoamine oxidase: enzyme characterization in cerebral microvessels and other tissues from six mammalian species, including human. AB - We studied the enzyme monoamine oxidase (MAO) in isolated cerebral microvessels, and in mitochondria-enriched brain and liver preparations from six mammalian species, including human. We also studied MAO distribution in various tissues and in discrete brain regions of the rat. MAO was assessed by measuring the specific binding of [3H]pargyline, an irreversible MAO inhibitor, and the rates of oxidation of known MAO substrates: benzylamine, tyramine, tryptamine, and 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Molecular forms of MAO were examined by using specific MAO inhibitors, and by polyacrylamide gel electrophoresis after [3H]pargyline binding. In general, the liver from all species had higher MAO levels than the brain, with minor variation among species in their brain and liver MAO content. However, there were remarkable species differences in brain microvessel MAO, with rat microvessels having one of the highest MAO activity among all tissues, whereas MAO activities in brain microvessels from humans, mice, and guinea pigs were very low. In most rat tissues, including the brain, there was a preponderance of MAO-B over MAO-A. The only exceptions were the heart and skeletal muscle. Estimates of MAO half-life in rat brain microvessels, rat brain, and rat liver indicated that microvessel MAO had a higher turnover rate. The reasons underlying the remarkable enrichment of rat cerebral microvessels with MAO-B are unknown, but it is evident that there are marked species differences in brain capillary endothelium MAO activity. The biological significance of these findings vis a vis the role of MAO as a "biochemical blood-brain barrier" that protects the brain from circulating neurotoxins and biogenic amines should be investigated. PMID- 2886557 TI - Glutamatergic denervation in Alzheimer's disease--a cautionary note. PMID- 2886558 TI - Evaluation of the endogenous glucocorticoid hypothesis of denervation atrophy. AB - We studied the effects of oral administration of RU38486, a potent and selective glucocorticoid antagonist, on muscle weight, non-collagen protein content, and selected enzyme activities (choline acetyltransferase, glucose-6-phosphate dehydrogenase, and glutamine synthetase) following denervation of rat skeletal muscle. Neither decreases in muscle weight, protein content, and choline acetyltransferase activity, nor increases in the activities of glucose-6 phosphate dehydrogenase and glutamine synthetase were affected by RU38486. These data do not support the hypothesis that denervation atrophy results from enhanced sensitivity of muscle to endogenous glucocorticoids. PMID- 2886559 TI - Somatostatin and Alzheimer's disease. PMID- 2886561 TI - Possible regression of left ventricular hypertrophy during antihypertensive treatment with diuretics and/or beta blockers. AB - The possible regression of left ventricular hypertrophy (LVH) during treatment with diuretics and/or beta blockers was assessed in 78 hypertensive patients by echocardiography. Five groups of patients were treated, respectively, with diuretics alone, chlorthalidone plus SR oxprenolol, acebutolol followed by atenolol, timolol alone, or atenolol alone. All patients, except those receiving acebutolol had a significantly reduced LV mass within 12 months. Acebutolol did not modify LV mass even after 24 months, in spite of its antihypertensive efficacy. The reduction of LV mass was due to a decrease in wall thickness after administration of beta blockers and a decrease in LV dimension after chlorthalidone. Normalization of LV mass (less than 130 g/m2) occurred only in 31% of patients. LV mass was not significantly modified in patients with normal mass in pretreatment condition. The decrease of LV mass correlated with a decrease in cardiac output but not with the reduction in blood pressure. In conclusion, LV systolic function showed a tendency toward improvement after long term antihypertensive therapy. PMID- 2886560 TI - A multicenter trial of low dose captopril administered twice daily in patients with essential hypertension unresponsive to beta blocker-diuretic treatment. AB - Two hundred and one patients with essential hypertension, whose supine diastolic blood pressure (SDBP) was greater than or equal to 95 mmHg following 2 weeks of treatment with the optimal dose of a beta blocker-diuretic combination (Phase 1), were randomly assigned to the addition of either 25 or 50 mg captopril BID for 6 weeks (Phase 2). At the end of Phase 2, the dose of captopril was doubled in the patients not normalized (SDBP greater than or equal to 95 mmHg) and maintained in the others (SDBP less than 95) for an additional 4 weeks (Phase 3). At the end of Phase 3, the beta blocker was withdrawn in the normalized (SDBP less than 95 mmHg) patients, and captopril plus diuretic was given for 4 weeks (Phase 4). The addition of captopril at either dose level led to a significant fall (p less than 0.01) in standing and supine diastolic and systolic blood pressure after the first 2 weeks of treatment. There was no significant difference in response between the two dose levels of captopril. At the end of Phase 2, 59.4% and 55.8% of patients, respectively, assigned to 25 and 50 mg captopril BID, were normalized. Doubling the dose of captopril (Phase 3) led to approximately an additional 30% of patients being normalized. At the end of Phase 4 (captopril plus diuretic) the SDBP was still less than 95 mmHg in 63% of patients, whereas it was increased in the others. Side effects were noted in 10 patients (5%). The incidence was similar in each treatment group, and a total of four patients (2%) were withdrawn due to side effects. PMID- 2886562 TI - Pattern formation in the striatum: developmental changes in the distribution of striatonigral neurons. AB - The striatum of the mammalian forebrain can be divided into 2 compartments, the patches and the matrix. We have investigated embryonic events involved in the formation of these compartments in rats. Early in development, dopamine fibers from the substantia nigra selectively innervate the patches. In the perinatal striatum, we observed a close match between the distributions of striatal cell bodies with axonal projections to the substantia nigra and patches of afferent dopamine fibers. Striatal cells projecting to the nigra are first seen in the ventrolateral striatum at embryonic day (E) 17. Striatonigral cell bodies are distributed homogeneously through the striatum from E18 to 19. At E20 and until postnatal day 4, these cell bodies are organized into discrete patches. After this time, striatonigral cell bodies assume the dense and homogeneous distribution characteristic of the adult striatum. A retrograde tracer injection in the nigra at E18 (during the early period of homogeneous striatonigral distribution) produces a patchy striatonigral distribution if the embryo is not sacrificed until E21. The number of retrogradely labeled striatonigral cell bodies in a midstriatal section, at times immediately before and after the early homogeneous to patchy changeover did not differ significantly. We suggest that the neurons of the patch compartment of the striatum are born first and project to the substantia nigra first. The patch neurons only become restricted to "patchy" areas as the later-born matrix neurons migrate out into the striatum. PMID- 2886563 TI - Development of a dopamine- and cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein (DARPP-32) in the prenatal rat central nervous system, and its relationship to the arrival of presumptive dopaminergic innervation. AB - The development of a dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein with an apparent Mr of 32,000 (DARPP-32) has been investigated in the central nervous system of the prenatal and newborn rat by immunocytochemical methods. DARPP-32 first appears in the rat brain at day 14 of gestation, in the anlage of the primary olfactory cortex and the caudate nucleus. Over the next few days, the number of immunoreactive cell bodies in these 2 areas, and in the olfactory tubercle and frontal cortex, increases rapidly. By the day of birth, most of the brain regions that will ultimately contain DARPP-32-positive somata already display a disposition toward DARPP-32-like immunoreactivity similar to that observed in the adult animal. In addition to the nuclei mentioned above, DARPP-32-containing cell bodies also appear over the intervening period in the olfactory nucleus, nucleus accumbens, central amygdaloid nucleus, lateral funiculus, and the choroid plexus and ependymal layers of the third, fourth, and lateral ventricles and the Sylvian aqueduct. Many of these immunoreactive cells disappear during subsequent postnatal maturation. DARPP-32-immunoreactive fibers were also observed in the prenatal and newborn rat CNS. As in the adult, the processes were observed in known target areas of the DARPP-32-containing neurons, namely, the globus pallidus, ventral pallidum, internal capsule, and substantia nigra. The ontogeny of tyrosine hydroxylase (TH)-like immunoreactivity was analyzed simultaneously. Of particular interest was the observation that the arrival within a given brain region of the presumed dopaminergic, TH-containing innervation, part of whose postsynaptic function is putatively mediated by DARPP 32, was preceded by at least 2 d by the appearance of the DARPP-32-containing cells. Moreover, the subsequent reorganization of the DARPP-32-positive somata within the caudate nucleus into distinct clumps also predated by 1 or 2 d the aggregation of the TH fibers into the same microzones. The development of DARPP 32-like immunoreactivity is mostly complete by the day of birth, and is consistent with its playing a role in mediating some of the postsynaptic actions of dopamine pathways. The appearance of this protein does not seem to be dependent on the presence of a dopaminergic innervation. PMID- 2886564 TI - Characterization of big dynorphins from rat brain and spinal cord. AB - To examine the processing of products of the dynorphin gene in the central nervous system, immunoreactive (ir) dynorphin (Dyn) A, Dyn B, Dyn A-(1-8), alpha- and beta-neo-endorphin (alpha- and beta-Neo) in rat brain and spinal cord were measured, using specific antisera after gel filtration and high-performance liquid chromatography (HPLC). Three peaks of Mr about 8, 4, and 2 kDa for ir-Dyn A and ir-Dyn B, and one peak of Mr less than 2 kDa for ir-Dyn A-(1-8), ir-alpha-, and ir-beta-Neo were found both in the brain and in the spinal cord. The 8 kDa peak was recognized by Dyn A and Dyn B antisera and, after hydrolysis by proline specific endopeptidase, by beta-Neo antiserum. The 8 kDa peak was recognized by a monoclonal antibody against the amino terminal sequence Tyr-Gly-Gly-Phe of all opioid peptides and by an antiserum directed toward the carboxyl terminus of Dyn B, indicating that it contains, from the amino terminal tyrosine of neo-endorphin to the carboxyl-terminal threonine of Dyn B, all 3 opioid peptide regions in the prodynorphin. By means of proline-specific endopeptidase hydrolysis, we also found a big dynorphin precursor (Mr approximately equal to 26 kDa) in both brain and spinal cord. PMID- 2886565 TI - The role of depolarization in the survival and differentiation of cerebellar granule cells in culture. AB - Cultures greatly enriched in granule cells from early postnatal cerebellum (P8) were grown in a medium containing fetal calf serum. Under the conditions used, nerve cells died, usually within a week, unless the K+ concentration in the medium was greater than or equal to 20 mM. The requirement for elevated [K+]e was manifested by about 3 d in vitro, and after this time continuous exposure to high [K+]e was essential for the survival of the granule cells. The initial morphological and biochemical maturation of the granule cells was similar in the presence and the absence of elevated [K+]e, suggesting that the dependence on depolarizing conditions develops in parallel with the expression of the differentiated characteristics of the cells. The positive effect of elevated [K+]e on granule cell survival was not influenced by preventing bioelectric activity in the cultures with TTX and xylocaine. On the other hand, depolarization-induced transmembrane Ca2+ flux was essential in securing the maintenance of the granule cells. Depolarized nerve cells were compromised when Ca2+ entry was blocked by elevated Mg2+, EGTA, or organic Ca2+ antagonists, while dihydropyridine Ca2+ agonists [BAY K 8644, (+)-(S)-202 79 1 and CGP 28392] were potent agents preventing nerve cell loss in the presence of 15 mM [K+]e, which was ineffective on its own. Calmodulin inhibitors (1 microM trifluoperazine or calmidazolium) blocked the beneficial effect of K+-induced depolarization on granule cells. The comparison of the timing of the differentiation and innervation of the postmitotic granule cells in vivo with the development of the K+ dependence in vitro would indicate that depolarization of the granule neurons in culture mimics the influence of the physiological stimulation in vivo through excitatory amino acid receptors, including N-methyl-D-aspartate receptors, involving Ca2+ entry and the activation of a Ca2+/calmodulin-dependent protein kinase. PMID- 2886566 TI - Neuroactive substances in inner ear extracts. AB - To identify the neurotransmitter released by sensory hair cells, as well as to find other substances that might influence neural function of the inner ear, we have prepared extracts from inner ears of fishes (which have large numbers of hair cells), fractionated the extracts, and studied the effects of the fractionated extracts on the discharge rate of afferent fibers innervating hair cells in the lateral line organ of the African clawed frog Xenopus laevis. The extracts contain active substances that do not bind to a cation-exchange resin at neutral pH. Gel-permeation chromatography suggests that at least 2 unidentified excitatory substances are present in the extracts: one of low molecular weight (Mr about 200) and one of high molecular weight (Mr less than or equal to 5000). Some extracts also contain a high-molecular-weight inhibitory substance (Mr greater than 5000). The low-molecular-weight active substance is detected in extracts of inner ear, but not in brain or muscle. The high-molecular-weight excitatory substance is present both in brain and in inner ear. PMID- 2886567 TI - Dietary protein level and aflatoxin B1-induced preneoplastic hepatic lesions in the rat. AB - Previous studies have shown that the development in rats of aflatoxin B1 (AFB1) induced gamma-glutamyl transpeptidase-positive (GGT+) foci, indicators of early preneoplastic liver lesions, was markedly greater when a 20% casein diet was fed than when a 5% casein diet was fed during the postinitiation period. In the present study, the dose-response relationship between dietary protein level (dose) and emergence of AFB1-induced GGT+ foci (response) in livers of rats was determined. Male Fischer-344 rats fed a 20% casein diet were orally administered AFB1 at a dose level of 250 micrograms/(kg X d) (10 doses over 12 d). One week after the last dose, the animals were divided into eight groups and fed isoenergetic diets containing either 4, 6, 8, 10, 12, 15, 20 or 30% dietary casein for the remaining 12 wk of the study. The development of GGT+ foci, as measured by number and percent of liver volume occupied, displayed a response with three discrete phases. The lowest dietary protein levels, 4, 6, 8 and 10% casein, were associated with a minimal level of GGT+ foci development. Between 10 and 12% dietary casein, the development of GGT+ foci sharply increased, up to the 15-30% dietary casein level. The sudden increase in the formation of GGT+ foci at 10-12% dietary casein was just above the level of dietary casein (6-8%) required for maximum body weight gain. These results in this animal model suggest that protein intake in excess of that required to sustain maximum growth rate may enhance AFB1-induced cancer development. PMID- 2886569 TI - Effect of indenolol treatment on beta-adrenergic receptors of polymorphonucleates in essential hypertension. AB - Indenolol is a new antihypertensive agent, whose beta 1-adrenoceptor antagonist properties combined with beta 2-adrenoceptor agonist properties have been shown by experimental studies in animals. Our previous work reported that in vivo beta adrenoceptor blocking drugs markedly increase the beta-adrenoceptor (BAR) number, without increasing BAR affinity. The aim of this study was to evaluate BAR density and affinity before and after indenolol therapy in membranes of polymorphonucleates (PMN) of patients with essential hypertension. Polymorphonuclear binding parameters were studied in 12 hypertensives (WHO stages I and II) after 14 days of placebo and after 21 days of indenolol therapy (120 mg once daily orally). Indenolol did not increase BAR number but significantly decreased (P less than 0.01) BAR affinity. On the basis of these data it is concluded that indenolol does not induce the same changes in PMN's BAR as previously observed with oxprenolol, propranolol and labetalol. This phenomenon may account for the absence of rebound effect after withdrawal of indenolol in hypertensives. PMID- 2886568 TI - Selective dopamine-1 receptor stimulation produces natriuresis by a direct tubular action. AB - Fenoldopam mesylate, a selective dopamine-1 (DA-1) receptor agonist, was infused intravenously in 10 normal male subjects in metabolic balance. The study was designed to determine the mechanism of dopamine-induced natriuresis. During fenoldopam infusion renal plasma flow (RPF) and urine flow rate manifested a biphasic response. The RPF rose from 344 +/- 39 to 481 +/- 44 ml/min (P less than 0.05), decreased to control levels, and then rose to 497 +/- 38 ml/min (P less than 0.05). Urinary sodium excretion (UNaV) and fractional excretion of sodium (FENa) demonstrated a sustained increase during DA-1 receptor activation. The FENa rose from 1.6 +/- 0.1 to 2.7 +/- 0.6% (P less than 0.05). Glomerular filtration rate (GFR), blood pressure and heart rate were unchanged. Our results, specifically the dissociation of RPF from UNaV and FENa, demonstrate in man that stimulation of renal tubular DA-1 receptors causes natriuresis. PMID- 2886570 TI - Pharmacological differentiation of pre- and post-junctional alpha 2 adrenoceptors. AB - It is now recognized that two post-junctional alpha-adrenoceptors mediate vascular constriction. The vascular alpha 2-adrenoceptors seem to be particularly sensitive to circulating catecholamine levels, in contrast to the alpha 1 adrenoceptors, which are activated primarily by neuronally released norepinephrine. Most alpha 2-adrenoceptor antagonists do not discriminate between the pre-junctional neuroinhibitory alpha 2-adrenoceptor and the post-junctional vascular alpha 2-adrenoceptor. However, we have synthesized and characterized a compound (SK&F 104078: 6-chloro-9-[(3-methyl-2-butenyl)oxy]-3-methyl-2,3,4,5 tetrahydro-1H-3- benzazepine) which is a potent antagonist at post-junctional vascular alpha 2-adrenoceptors in vitro but has no effect at pre-junctional neuroinhibitory alpha 2-adrenoceptors. The post-junctional selectivity of SK&F 104078 has been confirmed by in vivo studies determining pre- and post-junctional alpha 2-adrenoceptor antagonist activity in the pithed rat. The ability to selectively block post-junctional alpha 2-adrenoceptors offers a novel approach to antihypertensive therapy, since the vasoconstrictor effects of circulating catecholamines can be attenuated without influencing the feedback control of transmitter release operating via pre-junctional alpha 2-adrenoceptors, and excess sympathoadrenal tone can be reduced without affecting normal neurovascular transmission. PMID- 2886572 TI - Enhanced stimulus-induced neurotransmitter overflow in epinephrine-induced hypertensive rats is not mediated by prejunctional beta-adrenoceptor activation. AB - The present study examines the effect of 6-day epinephrine treatment (100 micrograms/kg per h, s.c.) on stimulus-induced (1 Hz) endogenous neurotransmitter overflow from the isolated perfused kidney of vehicle- and epinephrine-treated rats. Renal catecholamine stores and stimulus-induced overflow in the vehicle treated group consisted of norepinephrine only. However, epinephrine treatment resulted in the incorporation of epinephrine into renal catecholamine stores such that approximately 40% of the catecholamine present was epinephrine while the norepinephrine content was reduced by a similar degree. Total tissue catecholamine content of the kidney on a molar basis was unchanged. Stimulus induced fractional overflow of neurotransmitter from the epinephrine-treated kidneys was approximately twice normal and consisted of both norepinephrine and epinephrine in proportions similar to those found in the kidney. This difference in fractional overflow between groups was not affected by neuronal and extraneuronal uptake blockade. Propranolol had no effect on stimulus-induced overflow in either group. Phentolamine increased stimulus-induced overflow in both groups although the increment in overflow was greater in the epinephrine treated group. In conclusion, chronic epinephrine treatment results in enhanced fractional neurotransmitter overflow. However, neither alterations in prejunctional beta-adrenoceptor influences nor alterations in neuronal and extraneuronal uptake mechanisms appear to be responsible for this alteration. Furthermore, data obtained with phentolamine alone do not suggest alpha adrenoceptor desensitization as the cause of the enhanced neurotransmitter overflow after epinephrine treatment. PMID- 2886571 TI - Lymphocyte beta 2-adrenoceptors mirror precisely beta 2-adrenoceptor, but poorly beta 1-adrenoceptor changes in the human heart. AB - To study the relationship of changes in human lymphocyte beta-adrenoceptors to changes potentially occurring in solid tissues we studied 16 patients undergoing elective coronary artery bypass grafting and determined the density of lymphocyte beta 2-adrenoceptors [by (-)125I-iodocyanopindolol (ICYP) binding] in comparison to beta-adrenoceptor density and responsiveness (contractile responses to isoprenaline) in the corresponding right atria. Lymphocyte beta 2-adrenoceptor density (with a range of 278-2442 ICYP binding sites/cell) was significantly correlated with beta-adrenoceptor density in the corresponding atria (54.8-171.6 fmol ICYP bound/mg protein, r = 0.784, P less than 0.001). In these atria the levels of beta 1- and beta 2-adrenoceptors (assessed by non-linear regression analysis of competition curves of the selective beta 2-adrenoceptor antagonist ICI 188,551 with ICYP binding) were approximately .70 and 30%, respectively. Lymphocyte beta 2-adrenoceptor density, however, correlated significantly better with atrial beta 2-adrenoceptor (r = 0.8441; P less than 0.001) than beta 1 adrenoceptor (r = 0.6226, P less than 0.05) density. On 12 of the 16 atria (electrically driven with 1 Hz at 37 degrees C) isoprenaline (10(-9) to 3 X 10( 6) mol/l) caused positive inotropic effects. The maximum increase in contractile force evoked by saturating concentrations of isoprenaline (mean: 3.52 +/- 0.62 mN), however, correlated equally well with beta 1- and beta 2-adrenoceptor density in the corresponding atria (r = 0.6834 and 0.6567, respectively). These results indicate that changes in lymphocyte beta 2-adrenoceptors can be taken as a precise index of changes of beta 2-adrenoceptors in other (solid) tissues; beta 1-adrenoceptor alterations, however, are only poorly reflected in the lymphocytes. PMID- 2886573 TI - Differential haemodynamic effects induced by beta 1-(bisoprolol) or beta 2-(ICI 118,551) adrenoceptor blockade in man. AB - To characterize beta 1- and beta 2-adrenoceptor mediated effects in man the influence of the selective beta 1-adrenoceptor antagonist bisoprolol and the selective beta 2-adrenoceptor antagonist ICI 118,551 on changes in blood pressure, heart rate and lymphocyte beta 2-adrenoceptor density evoked by dynamic exercise or isoprenaline infusion was studied in 12 male normotensive volunteers. Bisoprolol administration (1 X 10 mg/day) did not affect lymphocyte beta 2 adrenoceptor density, while ICI 118,551 (3 X 25 mg/day) increased it by about 40%. Exercise as well as isoprenaline infusion caused 100% increases in lymphocyte beta 2-adrenoceptor density; these increases were completely abolished by ICI 118,551, but not affected by bisoprolol. ICI 118,551 markedly attenuated isoprenaline-induced decrease in diastolic blood pressure, but did not affect increase in systolic blood pressure; on the contrary, bisoprolol inhibited the isoprenaline-evoked increase in systolic blood pressure, but did not affect the decrease in diastolic blood pressure. ICI 118,551 antagonized the isoprenaline induced tachycardia much more potently than bisoprolol, while bisoprolol, but not ICI 118,551, suppressed exercise-induced tachycardia. It is concluded that exercise-induced tachycardia is mediated by cardiac beta 1-adrenoceptor stimulation, whereas isoprenaline-induced tachycardia is mediated by both beta 1- and beta 2-adrenoceptor stimulation. PMID- 2886574 TI - Normal serum gamma-glutamyl-transpeptidase activity identifies groups of infants with idiopathic cholestasis with poor prognosis. PMID- 2886575 TI - An investigation of executive processes in the problem-solving of attention deficit disorder-hyperactive children. PMID- 2886577 TI - Gastroschisis and extraabdominal ectopic testis: simultaneous repair. AB - During a 10-year span, three males with gastroschisis were seen in whom one of the testes exited through the paraumbilical opening with the exteriorized intestine. In each case, prior to correction of the abdominal wall defect, the testes (left side in 2, right side in 1) were placed into the ipsilateral scrotum and anchored. In the first child, the undescended gonad, very small at birth, continued hypoplastic at 1 year. The second patient (8 years) required a second stage orchidopexy at age 2 years. The third child, a 1.3-kg premature infant, has good testicular size and position at 6 1/2 years. Undoubtedly because of the magnitude of the main pathology, recommendations on how to handle the gonad in this association are not available. This report focuses on the simplicity of concomitant repair. A similar approach was employed in two children with omphalocele and undescended testes. PMID- 2886576 TI - Provocative testing for occult medullary carcinoma of the thyroid: findings in seven children with multiple endocrine neoplasia type IIa. AB - A rise in the serum calcitonin (CT) following provocative testing has facilitated making the diagnosis of occult medullary carcinoma of the thyroid (MCT) or C cell hyperplasia (CCH) in asymptomatic children of kindred with multiple endocrine neoplasia (MEN) type IIa. Findings were reviewed for seven children varying in age from 3 to 16 years screened at our institution between 1976 and 1986. Three had elevated basal calcitonin (S-CT). Six had significant elevation of calcitonin (delta-CT) after stimulation. Total thyroidectomy was performed in all seven. Five had MCT with bilobar involvement in three. CCH was present in all five. Two patients had no gross, microscopic, or immunohistochemical evidence of MCT or CCH. One of three had an elevated S-CT. The other had a significant delta-CT. All patients have normal postoperative S-CT and delta-CT. Our experience indicates the importance of beginning stimulation tests of affected kindred at less than 3 years of age. It appears, however, that neither elevated S-CT or positive delta CT are perfect predictors of parafollicular cell pathology. Solitary parathyroid enlargement, second thyroid malignancy, and branchial pouch anomalies may occur with MEN IIa. One patient with MCT had a focus of papillary carcinoma. One patient with primary hyperparathyroidism had a solitary enlarged parathyroid adenoma. Additional findings were the presence of nodules of ectopic thymus in close association with the thyroid gland in three patients. PMID- 2886578 TI - Inhalational medications for chronic asthma. PMID- 2886579 TI - British Pharmaceutical Conference Science Award lecture 1986. Order out of chaos. PMID- 2886580 TI - Mechanically strong films produced from cellulose acetate latexes. AB - Mechanically strong films, comparable with those obtained from organic solutions, can be produced from cellulose acetate latexes, a new type of dispersion, both by casting and spraying. The prerequisite conditions for high strength, which include choice of water-soluble plasticizers possessing some degree of volatility, are discussed. PMID- 2886581 TI - Structural and conformational analogy between cholecystokinin and ergopeptines. AB - The central nervous system (CNS) peptide cholecystokinin (CCK) and the ergopeptine alkaloids exhibit common pharmacology in the brain, particularly via catecholaminergic systems. We report here structural similarities between CCK and the ergot alkaloids, and the subsequent conformational analysis of the peptide undertaken to establish whether or not a three-dimensional relationship exists between the compounds. Two low-energy conformations of CCK that mimic the ergopeptine ergotamine are identified, one arising from an X-ray crystal structure and the other from a Dreiding model-based, computer-assisted search. The pharmacological, structural and conformational observations strongly support the hypothesis that CCK and the ergopeptines share common sites of action in the CNS. PMID- 2886582 TI - Problems of haemoglobin freeze-drying: evidence that water removal is the key to iron oxidation. AB - Formation of methaemoglobin during freeze-drying of oxyhaemoglobin raises the question of the cause and mechanism of the oxidation. Haemoglobin with or without lyoprotector (250 mM glucose or amino acid salt) has been subjected to freeze drying changes in either or both of two constraints--vacuum and rise in temperature. A rise in temperature from -40 to +10 degrees C had no substantial denaturing effect on haemoglobin whether protected or not. Maintenance of a vacuum over frozen haemoglobin for 18 h often produced subtotal desiccation. Unprotected haemoglobin was partially oxidized (39% MetHb) whereas protected haemoglobin was not (less than 4% MetHb). Haemoglobin was also dried by rapid dehydration of thin films in a stream of air at room temperature (20 degrees C). The methaemoglobin content was then 43% whereas the amino acid salt or glucose limited it at 4 and 7%, respectively. Haemoglobin is oxidized, therefore, only because of the removal of water. Protectors, not specific in structure and action, probably work by holding or reinforcing the critical number of hydration layers around haemoglobin. PMID- 2886583 TI - Effect of moderate haemodilution with Fluosol-DA or normal saline on low-dose phenytoin and (+/-)-5-(4-hydroxyphenyl)-5-phenylhydantoin kinetics. AB - Phenytoin kinetics were determined in the rat following moderate (50%) blood exchange with either Fluosol-DA or normal saline. Rats received an intravenous phenytoin dose (10 mg kg-1) 0.5, 24, 48, or 72 h after exchange and were compared with non-exchanged controls. Phenytoin t 1/2 was not altered by exchange with either fluid. Its Cl and Vd were decreased and AUC increased 24, 48, and 72 h after saline exchange and 24 h after Fluosol-DA exchange. (+/-)-5-(4 Hydroxyphenyl)-5-phenylhydantoin (HPPH), a major metabolite of phenytoin, showed a decreased t1/2 and VHPPH 24, 48, and 72 h after exchange with either fluid; t1/2 was also reduced 0.5 h after Fluosol-DA exchange. The decreased Vd and VHPPH may result from changes in cardiac output secondary to haemodilution, or may represent a redistribution in the microcirculation. Fluosol-DA appears to enhance phenytoin and HPPH metabolism 48 and 72 h after exchange. PMID- 2886584 TI - Evidence for tryptaminergic and noradrenergic involvement in the antisecretory action of morphine in the rat jejunum. AB - Experiments have been performed to determine whether the antisecretory (antidiarrhoeal) effect of morphine in the intestine is mediated by a direct action of morphine on enteric nerves. Rats were pretreated with 6-hydroxydopamine (6-OHDA) or p-chlorophenylalanine (PCPA) to deplete intestinal stores of noradrenaline and 5-hydroxytryptamine (5-HT). Intraperitoneal injection of 6-OHDA (3 doses at 50 mg kg-1) caused a selective reduction in the level of noradrenaline in the jejunum to 7.3% of control. Intraperitoneal injection of PCPA (200 mg kg-1) selectively reduced the jejunal level of 5-HT to 30.5% of control. Groups of rats that had been treated as described above were anaesthetized and then injected intravenously with saline or with blocking doses of either atropine (0.25 mg kg-1), hexamethonium (20 mg kg-1), ketanserin (30 micrograms kg-1), methysergide (30 micrograms kg-1), phentolamine (2 mg kg-1) or propranolol (1 mg kg-1). Following perfusion of the lumen of the jejunum, the rate of glucose absorption was measured to assess the integrity of the mucosa. Glucose absorption was unaltered in animals pretreated with hexamethonium and propranolol but there was a small enhancement in animals pretreated with atropine, PCPA, methysergide, 6-OHDA and phentolamine. The rate of net water absorption from the lumen of the jejunum and the rate of fluid secretion into the lumen following intra-arterial infusion of vasoactive intestinal peptide (VIP, 0.8 microgram min-1) were unaltered by any of the drug treatments. Intravenous injection of morphine (10 mg kg-1) did not alter the levels of noradrenaline or 5 HT in the whole jejunum. However, this dose of morphine did cause a 63.5% decrease in the VIP-induced change in water transport. This antisecretory effect of morphine was unaltered in animals pretreated with atropine, hexamethonium and propranolol. In contrast, methysergide, ketanserin and 6-OHDA abolished the antisecretory effect of morphine. PCPA and phentolamine produced a partial inhibition of morphine's antisecretory effect. It is concluded that morphine produces its antisecretory effect in the jejunum by activation of noradrenergic and tryptaminergic systems. PMID- 2886585 TI - The potentiation of phorbol ester-induced aggregation of human platelets by the prostaglandin endoperoxide analogue, U46619. AB - It was not possible to desensitize human blood platelets to 12-deoxyphorbol phenylacetate (DOPP) stimulation in a manner analogous with that to platelet aggregating factor (PAF), prostaglandin-endoperoxide analogue (U46619) or adenosine diphosphate (ADP). Platelets previously desensitized to U46619, when challenged with DOPP and ADP, showed an increased aggregation and release of 5 HT. Sub-threshold aggregating doses of U46619 also caused a potentiation of the platelet response and release reaction to DOPP. The concentration of U46619 used to pretreat platelets affected the extent of potentiation of platelet stimulation induced by DOPP. The degree of potentiation was also affected by the time interval between addition of U46619 and DOPP. U46619 did not potentiate the aggregating effects of PAF, or ionophore A23187. The stimulus potentiation of DOPP by U46619 was abolished by prostacyclin (PGI2) and an antibody to U46619, but was unaffected by indomethacin and CP/CPK. PMID- 2886586 TI - Comparative studies with the enantiomers of the glycol metabolite of propranolol and their effects on the cardiac beta-adrenoceptor. AB - The two enantiomers ((R)- and (S)-) of propranolol glycol, a metabolite of propranolol, have been synthesized, and their effects upon the beta-adrenoceptor studied by two methods. The ability of these compounds to antagonize the inotropic actions of isoprenaline was examined on spontaneously beating rat atrial preparations. Also, the effects of these enantiomers upon the binding of [3H]dihydroalprenolol to beta-receptors in rat cardiac ventricular membranes was studied. Experiments with the atria indicated that the (S)-glycol was a reversible competitive antagonist of isoprenaline with a potency approximately one thousand times lower than that of (+/-)-propranolol. In contrast, the (R) glycol appeared to act as an irreversible antagonist, producing complex dose response curves. The effects of these compounds to cause displacement of alprenolol binding were consistent with the organ bath data. The interaction of the (S)-glycol with the beta-receptor binding site was reversible (Ki of 27.6 +/- 4.2 microM) but less potent than that of (+/-)-propranolol (Ki of 0.99 +/- 0.07 nM). On the other hand, pretreatment of ventricular membranes with the (R) glycol, followed by extensive washing techniques, resulted in alprenolol binding which did not regain control values, providing further evidence for an irreversible effect upon the beta-receptor. The possible significance of these pharmacological actions of the two enantiomers is discussed in terms of the in vivo metabolic pathways for propranolol. PMID- 2886587 TI - A new method for measuring the free fraction of cyclosporin in plasma by equilibrium dialysis. AB - The free fraction of cyclosporin in plasma has been measured by equilibrium dialysis in steel chambers. Equilibration time was 16 h. The intra-assay coefficient of variation was 7%. The free fraction remained constant in plasma samples frozen for up to 6 months, and was independent of the total concentration within the therapeutic range. PMID- 2886588 TI - Dose-related inhibition of the drug-metabolizing enzymes of rat liver by the pyrrolizidine alkaloid, monocrotaline. AB - Adult, male Sprague-Dawley rats were given 0, 10, 20, 40 or 80 mg kg-1 of monocrotaline intraperitoneally and the following toxicity parameters determined 24 h post treatment. Compared with the control none of the doses caused significant change in either the relative liver weight or the hepatic microsomal protein concentration. Microsomal cytochrome P450 content and activities of benzphetamine N-demethylase and aniline hydroxylase did not differ from the control at 10 or 20 mg kg-1 dosage. But, there was a significant loss of cytochrome P450 at 40 and 80 mg kg-1 dosages and decrease in the activity of the two enzymes only at the highest dose. Similarly, the highest dose caused a marked elevation of serum sorbitol dehydrogenase and glutamic pyruvic transaminase activity suggestive of severe liver damage. PMID- 2886589 TI - Diazepam and desmethyldiazepam differ in their affinities and efficacies at 'central' and 'peripheral' benzodiazepine receptors. AB - The in-vitro binding characteristics of three different ligands ([ 3H]Ro 15-1788, [3H]Ro 5-4864 and [3H]flunitrazepam) and the structural requirements for binding to 'central' and 'peripheral' benzodiazepine receptors have been evaluated in rat cerebral cortex, cerebellum and adrenal glands. [3H]Ro 15-1788 binding was detectable only in the brain. Clonazepam was the most potent inhibitor followed by diazepam and desmethyldiazepam, which showed the same affinity, and by premazepam; Ro 5-4864 did not show appreciable affinity. The same pattern was seen for [3H] flunitrazepam binding in brain areas while in adrenal gland the inhibition pattern was exactly superimposable on that with [3H]Ro 5-4864 in all the areas considered (Ro 5-4864 greater than diazepam greater than desmethyldiazepam greater than clonazepam greater than premazepam). These data confirm and extend previous reports. A methyl group in position 1 enhances the affinity for peripheral benzodiazepine binding sites which are labelled in the adrenal gland by [3H]Ro 5-4864 and [3H]flunitrazepam; in brain areas, [3H]flunitrazepam, like [3H]Ro 15-1788, selectively labels central binding sites. Methylation in position 1 did not change the affinity for these sites. Desmethyldiazepam is less active than diazepam as an anticonvulsant and in other tests. In-vivo experiments were therefore carried out to assess the 'intrinsic activity' of desmethyldiazepam: it appeared that this compound acts as a partial agonist at central benzodiazepine receptors. PMID- 2886590 TI - The inhibition of monoamine oxidase by tricyclic antidepressants: the influence of the nature of the substrate and the source of the enzyme. AB - Five tricyclic antidepressants, amitriptyline, clomipramine, desipramine, imipramine and iprindole, have comparable potencies as inhibitors of monoamine oxidase in rodent brain and liver. With rodent brain, potency was always greater with phenethylamine as substrate than with benzylamine, and was generally least with 5-HT. With mouse liver, in which monoamine oxidase is mainly B type, potency with tyramine and dopamine as substrates was close to that found with phenethylamine. The kinetics of inhibition varied with both the substrate and the tissue, and were inconsistent with a simple ping-pong model for substrate oxidation. The relevance of these observations to clinical effectiveness is discussed. PMID- 2886591 TI - Pharmacokinetics and biliary excretion of rose bengal in rats with acute and chronic renal failure. AB - The effects of glycerol-induced acute renal failure (ARF) and surgically induced chronic renal failure (CRF) on the pharmacokinetics and biliary excretion of rose bengal have been examined in the rat. Both the pharmacokinetics and biliary excretion of rose bengal were unaltered in either ARF or CRF. The latter results in CRF contrast with those of Tse et al (1976, Int. J. Nucl. Med. Biol. 3: 134 137) who reported decreased removal of the dye from blood and reduced biliary excretion. In addition, rose bengal behaves differently from bromosulphophthalein and indocyanine green whose hepatic uptake and initial biliary excretion are known to be decreased in ARF. The results suggest that rose bengal may have a hepato-biliary transport route which differs from that of bromosulphophthalein and indocyanine green, and the findings also emphasize the selective nature of altered organic anion uptake by the liver in ARF. PMID- 2886592 TI - Effect of egg yolk lecithin on transdermal delivery of bunazosin hydrochloride. AB - Transdermal delivery of bunazosin HCl and the enhancing effect of egg yolk lecithin were examined using an in-vitro hairless mouse skin preparation and rabbits for in-vivo systemic absorption. The delivery of bunazosin in-vitro was small, but it was significantly enhanced when lecithin was incorporated into the same vehicle. This enhancing effect was confirmed with other drugs in-vitro. The enhancing ability was also seen in-vivo. Very little bunazosin was delivered from a propylene glycol suspension, but levels of 100-200 ng mL-1 were achieved by the incorporation of the lechithin. PMID- 2886593 TI - Relationship between progesterone suppression and pregnancy in rats. AB - Four luteolytic agents were administered to groups of pregnant rats to examine the quantitative relationship between serum progesterone levels and the maintenance of pregnancy. Each agent inhibited progesterone in a dose-dependent manner, however only three, azastene, thiosemicarbazone and dihydrotestosterone, adversely affected pregnancy. A statistical analysis of the data suggests that, regardless of the mechanism of action of a particular luteolytic agent, a treatment-induced depression of serum progesterone to concentrations less than 45% of that of the controls on day 11 of pregnancy is incompatible with pregnancy maintenance. PMID- 2886594 TI - Interactions of trimebutine with guinea-pig opioid receptors. AB - Affinities of trimebutine (TMB) and N-desmethyl trimebutine (NDTMB) for mu, delta and kappa opioid receptor subtypes have been examined using specific 3H-ligands and guinea-pig membrane. TMB and NDTMB showed a relative higher affinity for the mu receptor subtype although they were, respectively, 30- and 48-fold less active than morphine. The receptor selectivity index for mu, delta and kappa were 100:12:14.4 for TMB, 100:32:25 for NDTMB and 100:5:5 for morphine. The sodium shift ratio was 14 for TMB, 10 for NDTMB and 37 for morphine. These data show that (unlike morphine, a pure mu agonist) TMB and NDTMB can be classified as weak opioid agonists and confirm that peripheral opioid receptors mediate their gastrointestinal motility effects. PMID- 2886595 TI - Stereoselective pharmacological effects and benzodiazepine receptor affinity of the enantiomers of Go 4962. PMID- 2886596 TI - Re-evaluation of the metabolism and excretion of diethylpropion in non-sustained and sustained release formulations. AB - A direct gas chromatographic method for unstable amino ketones, using a neutral column and moderately alkaline conditions during extraction has been developed. Its application has given a new perspective to the relative importance of the metabolic routes in the complex metabolism of diethylpropion which after oral administration in man is rapid and extensive (only 3-4% of the drug remains unchanged). Mono-N-de-ethylation is the main pathway (about 35% of the dose). N De-ethylation is more important than carbonyl-reduction, occurring mainly with the unchanged drug (about 20% of the dose). Norephedrine, thought previously to be one of the main metabolites, has been shown to be present only in negligible amounts. About 30% of the dose, which cannot be accounted for as the sum of the amines recovered in urine, is probably metabolized by deamination, followed by oxidation and conjugation to give hippuric acid. PMID- 2886597 TI - A comparative study of the interaction of warfarin with human alpha 1-acid glycoprotein and human albumin. AB - The interaction of warfarin with human alpha 1-acid glycoprotein (alpha 1-AGP) and human albumin (HA) has been investigated using fluorescence and circular dichroism techniques. The fluorescence of warfarin is greatly enhanced following binding to alpha 1-AGP or HA, the binding constant for a single site being estimated by the Scatchard method. The binding constants for the two serum proteins are similar, but the thermodynamic parameters differ. The binding constants increase as the pH is raised to 9.0. Various basic drugs, such as chlorpromazine, propranolol and imipramine, markedly inhibited the binding of warfarin to alpha 1-AGP. But, some acidic drugs, including phenylbutazone, effectively displaced warfarin bound to HA. The difference in CD spectra observed for alpha 1-AGP and HA indicated that the drug-binding sites of the two proteins might have different asymmetries. It thus appears that the mode of interaction of warfarin with the two proteins differs. PMID- 2886598 TI - Effect of age on gastrointestinal and hepatic first-pass effects of levodopa in rats. AB - Presystemic elimination of levodopa (20 mg kg-1) has been studied in 5- to 104 week-old male Wistar rats. The gastrointestinal and hepatic contribution to the overall first-pass effect was estimated separately after the drug had been administered intravenously, orally and intraportally. The contribution of the gut to the overall first-pass effect of this drug was greater than that of the liver in any age-group of the rats. Both the overall and intestinal first-pass effects of levodopa were greatest in 11-week-old rats and relatively small in both young (between weeks 5 and 7) and aged (between weeks 52 and 104) rats. In contrast, the hepatic first-pass effect did not show any significant age-dependent change. Age-related change in the jejunal blood flow could not explain the unique age dependence in the intestinal first-pass metabolism of levodopa. However, the present age-dependence in the oral systemic availability of this drug between adult (11 weeks) and aged (52 to 104 weeks) rats was found to be similar to the tendency that has been reported between normal adult subjects and aged patients with Parkinson's disease. PMID- 2886599 TI - Amiodarone and desethylamiodarone tissue uptake in rats chronically treated with amiodarone is non-linear with the dose. AB - Four groups of rats were given amiodarone chronically at 25, 37.5, 50, 75 mg kg 1/12 h for 3 weeks; on day 21 the animals were killed and blood, plasma, heart, lung, liver and fat were collected and assayed for amiodarone and desethylamiodarone. Amiodarone plasma concentrations ranged from 0.74 to 4.68 micrograms mL-1 and desethylamiodarone from 0.08 to 2.05 micrograms mL-1. Plasma, blood and tissue concentrations of amiodarone and desethylamiodarone increased significantly with the dose. Blood/plasma and tissue/plasma partition ratios of amiodarone and desethylamiodarone increased significantly at the higher doses. Blood/plasma ratio was a good predictor of tissue/plasma ratios of amiodarone and its metabolite, except in fat. Total phospholipid concentrations in lung were correlated with amiodarone and desethylamiodarone concentrations in plasma, blood and lung. PMID- 2886600 TI - Ca2+ channel-blocking effect of the yohimbine derivatives, 14 beta benzoyloxyyohimbine and 14 beta-pho-nitrobenzoyloxyyohimbine. AB - Yohimbine possesses a relatively selective alpha 2-adrenoceptor antagonistic effect and a weak Ca2+ channel blocking activity, so two derivatives, 14 beta benzoyloxyyohimbine and 14 beta-rho-nitrobenzoyloxyyohimbine were compared with yohimbine using those parameters. The two derivatives blocked Ca2+-induced contraction of the rat perfused mesenteric vascular bed at 3 X 10(-6) M, and developed dose-dependent shifts of the dose-response curve to the right in concentrations from 3 X 10(-6) to 10(-5) M. Yohimbine showed a weak Ca2+ channel blocking effect only at a concentration of 10(-5) M. On the other hand, both derivatives at 3 X 10(-6) M did not affect the dose-response curve to noradrenaline-induced vasoconstriction. Furthermore, at 10(-8) M they had no effect on the dose-response curve to clonidine-induced inhibition of the twitch response of the rat isolated vas deferens evoked by electric stimulation, whereas yohimbine significantly attenuated clonidine-induced inhibition. These results indicate that introduction of bulky substituents into the 14-position of yohimbine intensely potentiated the Ca2+ channel-blocking effects and reduced alpha-adrenoceptor antagonistic effects compared with those of yohimbine, and suggest that chemical modifications of yohimbine may lead to structurally new types of Ca2+ channel-blockers. PMID- 2886602 TI - Activation of a myenteric 5-hydroxytryptamine-like receptor by metoclopramide. AB - Cholinergically mediated contractions were evoked by electrical field stimulation (EFS) of guinea-pig distal ileum longitudinal muscle-myenteric plexus strips. Metoclopramide, 0.1-100 microM, dose-dependently increased the contractions, probably by increasing acetylcholine (ACh) release; contractions evoked by exogenous ACh in the presence of tetrodotoxin were not increased by metoclopramide. 5-Hydroxytryptamine (5-HT) 0.3-30 nM similarly increased the height of the EFS-evoked contractions, although the maximum increase was less than for metoclopramide; higher concentrations of 5-HT (3 and 30 microM) had no effects or caused inhibition. The compound, ICS 205-930, 0.001-1 microM, had no effect on the EFS-evoked contractions and caused inhibition at higher concentrations. Preincubation of the tissues with 5-HT, 0.3-30 nM, did not affect the increase in EFS-evoked contractions caused by metoclopramide, 1 or 100 microM, whereas 5-HT, 3 and 30 microM, prevented the response caused by metoclopramide 1 microM, but not 100 microM. ICS 205-930, 0.1 microM, had no effect on the increase in EFS-evoked contractions caused by metoclopramide 1 or 100 microM. The drug, at least in low concentrations, may therefore increase cholinergically mediated contractions of guinea-pig ileum by stimulating 5-HT like receptors within the myenteric plexus, which differ from those antagonized by ICS 205-930. PMID- 2886601 TI - Effects of magnesium chloride on the contractile response of uterus to several agonists in Ca-free solution. AB - The effects of MgCl2 on the oestrogen-dominated rat uterus have been examined. Tissues were preincubated in a Ca2+- and Mg2+-free medium containing 3 mM EDTA. Most experiments were subsequently performed in a similar medium containing either no EDTA or EDTA (1 mM). When MgCl2 was added cumulatively (1-32 mM) no contractile responses were obtained in Ca,Mg-free medium or in Ca,Mg-free high K+ solution. When 2 mM CaCl2 was added, a sustained contraction was obtained. Subsequent addition of cumulative concentrations of MgCl2 caused concentration dependent relaxation. Oxytocin, 2 microM, produced a small and sustained contraction in a Ca,Mg-free medium. Addition of MgCl2, 2 mM, increased this contraction. In a Ca,Mg-free medium vanadate (8 X 10(-5)M) did not evoke spasm of uterine smooth muscle. After addition of MgCl2 in cumulative amounts (1-32 mM) in the presence of vanadate, a concentration-dependent contraction was obtained. The present work shows that in Ca-free solution, maintained contractions induced by oxytocin and vanadate are augmented by Mg2+. PMID- 2886603 TI - Gossypol: a potent inhibitor of PAF-acether- and leukotriene-induced contractions of guinea-pig lung parenchyma strips. AB - Gossypol, a substance extracted from cotton plants, markedly inhibited the contractile responses of guinea-pig lung parenchyma strips stimulated with leukotriene B4 (LTB4), leukotriene D4 (LTD4) and PAF-acether but not the responses to histamine (except at high concentration). It was slightly less potent than nordihydroguaiaretic acid (NDGA) and a PAF-antagonist (BN 52021). From previously reported effects of gossypol on the cyclooxygenase and lipoxygenases, and on the similarity of the inhibition produced by NDGA and gossypol on the lung parenchyma, it is suggested that the inhibition of the myotropic activity of the lung parenchyma by gossypol is due to interactions with the formation of cyclooxygenase products within the guinea-pig lung. PMID- 2886604 TI - Extracts of feverfew may inhibit platelet behaviour via neutralization of sulphydryl groups. AB - It has been suggested that extracts of feverfew may inhibit platelet behaviour via effects on platelet sulphydryl groups. In the present study we have obtained evidence for such a mode of action. Compounds that contain sulphydryl groups such as cysteine and N-(2-mercaptopropionyl)glycine prevented the inhibition of platelet behaviour by feverfew. Feverfew and parthenolide (one of the active components of feverfew) dramatically reduced the number of acid-soluble sulphydryl groups in platelets. This effect occurred at concentrations similar to those that inhibited platelet secretory activity. Feverfew itself did not induce the formation of disulphide-linked protein polymers in platelets but polymer formation occurred when aggregating agents were added to feverfew-treated platelets. Feverfew evoked changes in the metabolism of arachidonic acid that were similar to those observed in glutathione-depleted platelets. PMID- 2886605 TI - Physicochemical investigations of dipolar aprotic solvents as potential cholelitholytic agents. AB - A number of dipolar aprotic solvents have been examined as potential co-solvents for gallstone dissolution. The power of these agents to solubilize such gallstone components as cholesterol, calcium carbonate, calcium palmitate and palmitic acid was determined and compared with that of monooctanoin (Capmul), using the synthetic solubility method. The solubilities of cholesterol and palmitic acid were greater in the N-methyl, N-ethyl and N-butylpyrrolidone derivatives than in monooctanoin. In contrast, the solubilities of the calcium salts were very low (less than 0.25% w/w) in all solvents examined. The influence of N methylpyrrolidone (NMP) on both the in-vitro dissolution of cholesterol from gallstones and the decrease in stone weight with time was determined. NMP proved to be a better solvent than monooctanoin for human stones. NMP, which is miscible with water and monooctanoin, may have potential as a co-solvent in the design of solvent systems for gallstones. PMID- 2886606 TI - Studies on thyrotropin-releasing hormone-induced micturition in cats. AB - In unanaesthetized cats micturition produced by thyrotropin-releasing hormone (TRH) was investigated after its injection into the cerebral ventricles through chronically implanted cannulae. TRH in doses from 0.1 to 1.0 mg evoked dose dependent micturition. In cats treated with intracerebroventricular (i.c.v.) reserpine and 6-hydroxydopamine, but not with i.c.v. 5,6-dihydroxytryptamine and hemicholinium, the micturition caused by i.c.v. TRH was abolished. Chlorpromazine and antazoline injected into the cerebral ventricles prevented the micturition induced by i.c.v. TRH. On the other hand, mecamylamine, yohimbine, propranolol, atropine and methysergide injected i.c.v. had virtually no effect or partially antagonized the micturition evoked by TRH similarly injected. It is apparent therefore that centrally induced TRH micturition could be related to central catecholaminergic mechanisms. PMID- 2886607 TI - The differential cytotoxicity of antiseptic agents. AB - The cytotoxicity of the antiseptic agents noxythiolin and chlorhexidine has been evaluated in-vitro using a range of tissue culture cell lines of differing degrees of neoplasticity. Noxythiolin appeared more cytotoxic than did chlorhexidine when tested against established neoplastic cell lines. By contrast, noxythiolin was not cytotoxic to normal control (non-neoplastic) cells. For chlorhexidine, the cytotoxic activity against control cells was similar to that observed for neoplastic cell lines. The results confirm an earlier observation of limited antitumour activity of noxythiolin solutions and, on the basis of differential cytotoxicity, confirm that noxythiolin is free from adverse effects against normal tissues and is safe for use as an antimicrobial agent applied to peritoneal surfaces and the healing wound. PMID- 2886608 TI - The oral clearance of zinc and triclosan after delivery from a dentifrice. AB - Oral delivery and retention of zinc and triclosan were measured in man after use of an anti-plaque dentifrice containing these antibacterial agents. Triclosan (25% of the dose) and zinc (24%) were retained in the mouth immediately after toothbrushing and a single mouthrinse. Salivary concentrations fell from 7.5 micrograms g-1 (triclosan) and 7.0 micrograms g-1 (zinc) after 5 min to 0.5 micrograms g-1 (triclosan) and 1.2 micrograms g-1 (zinc), 2 h after brushing. PMID- 2886609 TI - Antiarrhythmic effect of desethylamiodarone in conscious rats. AB - The effect of desethylamiodarone, a metabolite of amiodarone, was studied in the early phase of arrhythmias induced by coronary artery ligation in conscious rats. Desethylamiodarone pretreatment improved survival without altering the occurrence of different types of arrhythmias during the first 20 min after coronary ligation. It was concluded that desethylamiodarone may contribute to the antiarrhythmic effect seen after chronic amiodarone treatment. PMID- 2886610 TI - The influence of drug sorption on pharmacokinetic studies of chlormethiazole and lignocaine. AB - The influence of drug sorption on the measurement of dose and blood concentrations during pharmacokinetic studies of chlormethiazole and lignocaine in a chronically catheterized sheep preparation has been examined. There was no sorption to soda glass tubes, borosilicate glass volumetric flasks or soda glass microlitre syringes but minor sorption to polypropylene syringes, polypropylene pipette tips and rubber bottle stoppers after 240 min contact. During infusions through administration sets including either polyvinyl chloride or polyethylene catheters, no significant loss of lignocaine occurred, but only 41.7-63.9% of the chlormethiazole dose was delivered. No significant decreases in either drug occurred from blood sampled through an intravascular catheter and stopcock system. There was negligible degradation of the samples over 4 h. Sorption of chlormethiazole or lignocaine to the laboratory equipment used was not a significant source of error but polyvinyl chloride infusion catheters could result in significant reductions in chlormethiazole dose. PMID- 2886611 TI - A gamma scintigraphic evaluation of the precorneal residence of liposomal formulations in the rabbit. AB - Multilamellar liposomes were prepared from dipalmitoyl phosphatidylcholine or egg lecithin in combination with cholesterol and either dicetyl phosphate or stearylamine. The size and charge of the colloidal preparations were characterized before labelling with [111In]8-hydroxyquinoline. Freshly labelled liposomes were instilled into the eyes of unanaesthetized NZW rabbits and their disposition and drainage followed using gamma scintigraphy. A positive surface charge was found to affect significantly liposomal drainage rate, whereas an increase in size restricted drainage from the inner canthal region. Drainage of the suspending medium was directly compared with liposomes by labelling the medium with [99mTc] sodium pertechnetate and following the simultaneous change in removal of 99mTc and 111In from the precorneal area. Slower drainage rates were obtained for the suspending medium compared with solutions of the isotopes suggesting that the liposomes restricted solution drainage. PMID- 2886612 TI - Stimulant action of pethidine on the pregnant rat uterus in-vitro. AB - Pethidine's stimulant action on the 22-day pregnant rat isolated uterus does not involve receptors sensitive to methysergide and is unlikely to involve the synthesis and release of endogenous prostaglandins. The sensitivity of pethidine induced contractions to verapamil suggests that mobilization of extracellular calcium is necessary for pethidine's action. PMID- 2886613 TI - Autoregulation of renal blood flow during the infusion of acetylcholine or carbachol in anaesthetized dogs. AB - Whether renal blood flow autoregulation is abolished by acetylcholine was re examined by kidney perfusion experiments in anaesthetized dogs. Renal blood flow was dose-dependently increased by the renal arterial infusion of acetylcholine (2 and 5 micrograms min-1) or another muscarinic agent, carbachol (2 and 5 micrograms min-1) and was maintained at an increased level during the infusion. When perfusion pressure was changed stepwise between 60 and 200 mmHg, the infusion of acetylcholine or carbachol caused no impairment of autoregulation. It is concluded that autoregulation is independent of muscarinic stimulation of vascular smooth muscle in the kidney. PMID- 2886614 TI - Evaluation of sorghum starch as a tablet disintegrant and binder. AB - The starch prepared from the seeds of Sorghum bicolor, Moench has been evaluated as a disintegrant and binder in tablets of magnesium sulphate, calcium carbonate, sulphadimidine, and chloroquine phosphate to represent soluble and insoluble inorganic and organic substances. The starch performed as well as maize starch in binding and disintegrating properties and better than acacia as binder. PMID- 2886615 TI - Punch velocities during the compaction process. AB - Velocities achieved by the upper punch of an eccentric tablet press during compaction have been compared with those predicted by equations describing the movement of the punch in an empty die. Up to the point of maximum punch penetration, actual speeds are invariably less than the predicted speed, the magnitude of the deceleration being determined by the machine speed and applied force. As the punch withdraws from the die, its speed can exceed that predicted on theoretical grounds, due to the elastic expansion of the tablet assisting punch ejection. PMID- 2886617 TI - Antinociceptive effects of (+/-)-, (+)- and (-)-nefopam in mice. AB - The antinociceptive activity of (+/-)-, (+)- and (-)-nefopam in mice has been examined using the hot-plate, formalin and tail-flick tests. Nefopam was administered by the intraperitoneal, intracerebroventricular (i.c.v.) and intrathecal (i.th.) routes. Intraperitoneal injection of (+/-)-nefopam (10-20 mg kg-1) had powerful analgesic effects in the hot-plate and formalin tests. In the tail-flick test it produced a weak, but significant elevation of the response latencies. In spinalized animals, however, the effect was abolished, indicating that nefopam prolonged the tail-flick latencies by activation of descending pain modulating pathways. (+/-)-Nefopam (5-20 micrograms) elicited analgesia in the hot-plate test after i.c.v. or i.th. injection. These findings suggest that nefopam has both a spinal and a supraspinal site of action. (+)-Nefopam was significantly more potent than (-)-nefopam after both systemic and central administration. PMID- 2886616 TI - Some aspects of the inhibitory activity of hypolaetin-8-glucoside in acute inflammation. AB - Hypolaetin-8-glucoside (H-8-G) has been examined for its mode of action in several models of acute inflammation. Its anti-inflammatory activity in carrageenan-induced inflammation of the rat hind-paw is not affected either by adrenalectomy or by phentolamine given with propranolol. H-8-G and its aglycone, hypolaetin, did not antagonize the actions of histamine, 5-hydroxytryptamine (5 HT), bradykinin or prostaglandin E2 (PGE2) on various smooth muscle preparations in-vitro, but protected erythrocytes from heat-induced lysis. The glycoside was more potent than troxerutin on capillary permeability increased by histamine and exerted inhibitory effects on protein exudation, leucocyte migration and beta glucuronidase activity in the carrageenan air pouch, thereby showing some difference from indomethacin. These results are discussed in relation to the features of non-steroidal anti-inflammatory drugs (NSAID) and flavonoid anti inflammatory actions. PMID- 2886619 TI - Comparative studies of cardiodepressant drugs on contraction dynamics and electrophysiological parameters of cardiac tissues at pH 7.4 and 9. AB - The effects of propranolol, amethocaine (tetracaine), lignocaine (lidocaine), procaine and benzocaine on force of contraction and action potential parameters of guinea-pig left atria and papillary muscles have been investigated at pH 7.4 and 9. All the drugs decreased the force of contraction of both preparations. Their biological activities correlated with their lipid/buffer partition coefficients and with their ability to change the surface potential of liposomes. The sequence of activities is as follows: propranolol greater than amethocaine greater than lignocaine greater than benzocaine greater than procaine. Uncharged benzocaine had no effect on the liposome surface charge. Biological and physicochemical effects obtained at pH 9 were higher than those observed at pH 7.4. Action potential amplitude and Vmax were decreased by all the drugs except benzocaine. At pH 9, the action potential duration was generally shortened, except by amethocaine and procaine; both caused a prolongation of the action potential at 90% repolarization. PMID- 2886618 TI - Effects of nicorandil and verapamil, antianginal agents, on plasma digoxin concentrations in rats and dogs. AB - The effects of equihypotensive doses of nicorandil and verapamil on plasma digoxin concentrations have been assessed in rats and dogs. In a single digoxin dose study, digoxin (1 mg kg-1) alone, or in combination with nicorandil (5 mg kg 1) or verapamil (25 mg kg-1) was given orally to rats. When given chronically to rats, a single dose of digoxin (1 mg kg-1) orally for 7 consecutive days was followed, on day 8, by digoxin alone, or together with nicorandil (5 mg kg-1) or verapamil (25 mg kg-1). In dogs, a loading dose of digoxin (50 micrograms kg-1) was given orally on day 1, then 25 micrograms kg-1 was administered for the following 6 days. On day 8, digoxin (50 micrograms kg-1) was given with nicorandil (5 mg kg-1) or verapamil (20 mg kg-1). In rats, the AUC0-24 and Cmax of plasma digoxin were enhanced significantly by coadministration of verapamil, but not by nicorandil. In dogs, verapamil significantly increased the Cmax of plasma digoxin, but not the AUC. Nicorandil had no effect on either parameter. PMID- 2886620 TI - Studies on the mechanisms of action of activated charcoal on theophylline pharmacokinetics. AB - Oral administration of repeated doses of activated charcoal to volunteers and dogs significantly increased the systemic clearance of intravenously administered theophylline and decreased its elimination half-life. This effect is most likely to be due to theophylline entering the gut and being adsorbed onto the charcoal. The mechanism by which intravenously administered theophylline enters the gut has been examined. Its biliary excretion after intravenous administration to patients with T-tube biliary drainage accounted for 0.28% of the dose and a similarly small biliary excretion was found in dogs. In the latter total biliary diversion had no effect on the clearance or half-life of theophylline after intravenous administration. In two dogs the theophylline content of jejunal aspirate was comparable with that of simultaneously withdrawn venous plasma samples. These results suggest that the presence of charcoal in the gut represents a sink adsorbing theophylline entering the lumen by diffusion across the intestinal wall, and by this mechanism it increases clearance of the drug even after intravenous administration. PMID- 2886621 TI - Probenecid inhibition of the renal excretion of dyphylline in chicken, rat and man. AB - The effect of probenecid on the renal excretion of dyphylline was studied in chicken, rat and man. Dyphylline was found to be actively excreted when measured by the Sperber preparation in hens, the isolated perfused kidney of the rat and clearance studies in man. In each study probenecid significantly decreased dyphylline excretion demonstrating that dyphylline occupied the renal organic anion transport system. This same drug interaction, at the level of the renal excretory system, in these three species occurred at comparable concentrations of dyphylline and probenecid. PMID- 2886622 TI - Enhanced penetration of mitomycin C through hairless mouse and rat skin by enhancers with terpene moieties. AB - The effects of four new percutaneous absorption enhancers containing an azacyclo ring and terpene chain (1-geranylazacycloheptan-2-one (GAH), 1 farnesylazacycloheptan-2-one (FAH), 1-geranylazacyclopentan-2,5-dione (GAPD), and 1-farnesylazacyclopentan-2-one (FAP] and 1-dodecylazacycloheptan-2-one (Azone) on the percutaneous penetration of mitomycin C (MMC) through hairless mouse and rat skin in-vitro has been investigated. GAH, FAH, FAP and Azone enhanced MMC penetration by 20 to 60 times that of the control (ethanol). During the early part of the experiments, when the sink condition was maintained, FAH was the most effective for hairless mouse skin, whereas Azone showed the highest effect in the rat skin. The enhancing effect of GAPD was only about half that of the other enhancers, suggesting the importance of the polar group of the ring moiety in these compounds. The penetration of MMC through rat skin was also increased by pretreatment with these compounds, suggesting that the enhancers had a direct effect on the skin. PMID- 2886623 TI - Effect of penetration enhancers on the permeation of mannitol, hydrocortisone and progesterone through human skin. AB - Mannitol, hydrocortisone and progesterone were selected as model penetrants to assess the mode of action of eight potential penetration enhancers in human skin. Their partition coefficients, octanol: water and stratum corneum: water were measured and correlated with their postulated routes of penetration through human skin. The results suggest that mannitol penetrated via a polar route, hydrocortisone by a mainly lipid route and progesterone via a lipid pathway but its penetration rate was probably affected by aqueous layers. From permeation studies through cadaver skin in which an in-vivo mimic method was used, it was concluded that the penetration enhancers fell into three main categories: solvents which enhanced permeation of polar and non-polar compounds e.g. 2 pyrrolidone, N-methylpyrrolidone, N-methylformamide and propylene glycol plus Azone; enhancers which preferentially affected the polar route e.g. propylene glycol plus decylmethylsulphoxide, and accelerants which mainly modified the non polar route e.g. propylene glycol plus oleic acid, propylene glycol alone and, to a limited extent, water. PMID- 2886624 TI - Casting solvent effects on the permeability of polymer films of differing quaternary ammonium (cation) content. AB - Films of certain acrylate-methacrylate copolymers of varying cation (quaternary ammonium) content were cast from three different solvents: acetone, chloroform, and ethanol; their permeability to urea was determined at 30 degrees C. In films containing 66 mole cation mol-1 polymer chain, and cast from acetone, chloroform or ethanol, the permeation rates were 480,900 and 2807 mg h-1, respectively. Differences in permeation rates were however less significant when polymers of cation content lower than 46 mole cation mol-1 polymer chain were used to form films. This observation may relate to differences in the degree of dissociation of the polymer in the different solvents. PMID- 2886625 TI - A high molecular weight form of pancreatic polypeptide was present in USP insulin and is absent in a more recent insulin preparation. AB - The concentrations and molecular forms of pancreatic polypeptide (PP) and glucagon were determined in USP XX and single-peak insulin preparations. In USP insulin the concentration of PP was 7 ng mg-1 insulin; on gel chromatography the PP immunoreactivity fractionated into two peaks of about equal size. One of the PP peaks was in the region of 4200 dalton PP, and the other PP peak eluted earlier in the region of a 7000-10,000 dalton peptide. The concentration of PP in single-peak insulin was 0.8 ng mg-1 insulin; the immunoreactivity eluted in a single peak in the region of [125I]PP. The concentration of glucagon in each preparation was 55 ng mg-1 insulin. On gel chromatography the immunoreactive glucagon in each insulin preparation eluted in the region of [125I]glucagon. PMID- 2886626 TI - Measurement ex-vivo of the inhibition of fatty acid biosynthesis by bezafibrate administration in different rat tissues. AB - The action of bezafibrate on fatty acid biosynthesis pathways has been examined in rat tissues. The drug abolished the induction of fatty acid synthesis that occurs on refeeding the animals with a high carbohydrate diet and by insulin administration in liver and adipose tissue. The rates of fatty acid biosynthesis in these tissues were estimated from the incorporation of 3H into lipids from 3H2O. PMID- 2886627 TI - Gastric mucosal cytoprotection in the rat by cysteine. AB - The free radical scavengers methyl-methionine sulphonium bromide and cysteine (5%) protected the rat gastric mucosa against ischaemic injury produced by reserpine (5 mg kg-1 i.p.). Pretreatment with 1 mL of 5% cysteine by gavage completely protected against injury rats with no ligation and 70% of rats with pyloric ligation after they had been given aspirin (200 mg kg-1 by gavage), a dose that produced gastric mucosal injury in 40% of rats with no ligation and 70% of rats with pyloric ligation after 4 h. Ethanol (1 mL of 40% solution by gavage) after 1 h produced gastric mucosal injury in all animals and pretreatment with 1 mL of 5% cysteine by gavage completely protected 80% of non-ligated and 70% of pyloric-ligated rats against this injury. This protection was not associated with any significant effect on H+ output. The data suggest that cysteine maintains gastric mucin by a mechanism independent of acid secretion. PMID- 2886628 TI - The sorption of nitroglycerin by infusion sets. AB - The sorption of nitroglycerin, from 5% glucose solution, by infusion sets was investigated under simulated perfusion conditions. Several burettes, sets and catheters were evaluated. The stability of the drug in the presence of glucose was also determined. High density polyethylene and glass proved satisfactory for its perfusion in solutions. A method for the evaluation of its uptake under simulated perfusion conditions is described. PMID- 2886630 TI - Mean residence time for drugs subject to reversible metabolism. AB - Conventional methods based on moment analysis lead to biased estimates of the mean residence time for drugs subject to reversible metabolism. A stochastic approach is described which enables unbiased estimation of the mean residence time. PMID- 2886629 TI - Inhibition of basal and insulin-stimulated gastric acid secretion by phenoxybenzamine or phentolamine. AB - The present study in the rat was undertaken to investigate the possible involvement of alpha- and beta-adrenoceptors in mediating gastric acid secretion in response to insulin-hypoglycaemia. Phenoxybenzamine, 15 mg kg-1, depressed the basal acid secretion to a level similar to that associated with vagotomy; phentolamine, 15 mg kg-1, had a similar effect. Insulin (1 unit kg-1) significantly stimulated gastric acid secretion. Vagotomy or phenoxybenzamine or phentolamine, 15 mg kg-1 prevented this action. The beta-adrenoceptor blocking drug, propranolol, 5-15 mg kg-1, had no significant effect on the basal acid secretion or its stimulation by insulin. The similarity in action between vagotomy and large doses of phenoxybenzamine and phentolamine suggests that, in the rat, vagal alpha-adrenoceptor stimulation is involved in the mechanisms of basal and insulin-stimulated gastric acid secretion. PMID- 2886632 TI - Fenfluramine antagonizes the stimulation of food intake induced by the putative 5 hydroxytryptamine1A agonist, isapirone, in non-fasted rats. AB - Isapirone, a 5-hydroxytryptamine1A receptor agonist, stimulated food intake in non-fasted rats in a dose-dependent manner (1, 3 and 10 mg kg-1 s.c.). Fenfluramine, an antiobesity agent and a 5-HT releaser, at 3 and 10 mg kg-1 s.c. antagonized the isapirone-induced (3 mg kg-1 s.c.) feeding. These results are consistent with the known inhibitory role of 5-HT in the control of food intake in rats. PMID- 2886631 TI - Anti-inflammatory activity of a polysaccharidic fraction of Echinacea angustifolia. AB - The anti-inflammatory activity of a polysaccharidic fraction (EPF) obtained from Echinacea angustifolia roots has been examined using the carrageenan paw oedema and the croton oil ear test. EPF (0.5 mg kg-1 i.v.) almost inhibited the carrageenan-induced oedema over 8 h and furthermore, EPF, topically applied, inhibited mouse ear oedema induced by croton oil. EPF also reduced the leukocytic infiltration of the croton oil dermatitis, evaluated both as peroxidase activity and histologically. After topical application EPF appears to be slightly inferior in potency to indomethacin. The results suggest that the anti-inflammatory activity of E. angustifolia resides in its polysaccharidic content. PMID- 2886633 TI - Auranofin inhibits the active uptake of bile acid by rat ileum. AB - Auranofin in the mucosal fluid inhibited the active Na+-dependent absorption of taurocholic acid by everted sacs of rat ileum. It did not however, affect the passive uptake of taurocholic acid by sacs of mid-intestine. The inhibition by auranofin of active bile acid absorption could result from its previously demonstrated ability to inhibit Na+, K+-ATPase activity. A reduction in the reabsorption of bile acids by the ileum may contribute to the diarrhoea experienced by some patients taking auranofin. PMID- 2886634 TI - Direct vasomotor effects of theophylline and enprofylline on human coronary artery in-vitro: comparison with feline coronary and cerebral arteries. AB - The vasomotor effects of theophylline and enprofylline were investigated on circular segments of human coronary artery taken 6 h after death. Isolated arterial segments were examined using a sensitive myograph and isometric contractions were recorded with Grass transducers. The results were compared with those obtained in feline coronary and cerebral arteries. Theophylline and enprofylline induced pronounced relaxation of all types of precontracted arteries. In feline cerebral arteries the potency for eliciting relaxation was slightly higher for theophylline compared with enprofylline, while there was no difference in potency for the methylxanthines in coronary arteries. Prostaglandin F2 alpha frequently induced rhythmic contractions in human, but not in feline coronary arteries. Theophylline increased the amplitude of the rhythmic contractions while this was not seen following administration of enprofylline. Whether this mode of activity by theophylline contributes to its arrhythmogenic properties in-situ requires clarification. PMID- 2886635 TI - Mu opioid antagonist properties of a cyclic somatostatin octapeptide in vivo: identification of mu receptor-related functions. AB - We have shown previously that D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (CTP) produces selective antagonism of mu, but not delta or kappa, opioid receptor selective ligands in the guinea pig ileum and mouse vas deferens bioassays, and in radioligand binding assays using homogenized rat brains. In the present study we characterized the agonist and opioid antagonist profile of CTP in analgesic (hot-plate test, abdominal stretch test) and in gastrointestinal assays (transit time test) in mice. CTP was a potent antagonist of the supraspinal and spinal analgesic effects of the mu selective agonist [MePhe3, D-Pro4]morphiceptin (PL017) in both assays. The gastrointestinal antitransit actions of PL017 were also antagonized by CTP at both supraspinal and spinal sites. CTP did not alter the effects of the kappa agonist trans-3,4-dichloro-N-methyl-N-(2-(1 pyrolidinyl)cyclohexyl)benz eneacetamine in any test. Surprisingly, CTP also antagonized the analgesia produced by i.c.v. and intrathecal administration of [D Pen2, D-Pen5]enkephalin (DPDPE), a highly delta selective agonist, in both analgesic tests. Differential antagonism of DPDPE, but not PL017, by the delta selective antagonist N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH in the hot-plate test indicates that PL017 and DPDPE may act at separate receptors to produce analgesia (mu and delta, respectively). In contrast, CTP did not reverse the gastrointestinal antitransit effects of intrathecal DPDPE. Schild analysis of the interactions of CTP with supraspinal mu and delta agonists in the hot-plate test indicated that although CTP antagonized PL017 in a competitive fashion (Schild slope = -1.0), the interaction of CTP with DPDPE was not competitive (Schild slope = -0.5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886636 TI - (R)-nipecotic acid ethyl ester: a direct-acting cholinergic agonist that displays greater efficacy at M2 than at M1 muscarinic receptors. AB - Previous reports have suggested that the ethyl ester of (R)-nipecotic acid ethyl ester [(R)-NAEE] displays cholinomimetic properties in vivo. The present study was undertaken to characterize more fully this action by examining the effects of (R)-NAEE in a number of pharmacological and biochemical tests of cholinergic action. (R)-NAEE was found to produce negative inotropic and chronotropic effects on the guinea pig atria (pD2 = 5.91 and 5.62, respectively), and was capable of stimulating contractions in the guinea pig ileum (pD2 = 5.95) and rat jejunum (pD2 = 5.40) at concentrations similar to bethanechol. Both the cardiac and intestinal effects of (R)-NAEE were reversed by atropine. Moreover, (R)-NAEE competed with N-[3H]methylscopolamine and [3H]pirenzepine for muscarinic binding sites in a variety of tissues. Like carbachol, (R)-NAEE inhibited GTP-stimulated adenylate cyclase in rat striatal membranes (EC50 = 52 microM), whereas, unlike carbachol, (R)-NAEE was unable to stimulate inositol phosphate accumulation in rat cerebral cortical slices, behaving as an antagonist in this latter system (pA2 = 5.0). The results indicate that (R)-NAEE interacts directly with cholinergic muscarinic receptors, being an agonist for the M2 subtype and an antagonist at M1 sites. PMID- 2886637 TI - Effect of inhibition of gamma-glutamyltranspeptidase on biliary and urinary excretion of glutathione-derived thiols and methylmercury. AB - Acivicin (AT-125; 6.25-200 mumol/kg i.v.) inhibited hepatic, biliary and renal gamma-glutamyltranspeptidase (GGT) activity up to 88, 99 and 97%, respectively, in 4-week-old rats. This inhibition of GGT by acivicin resulted in a 10- to 12 fold increase in the biliary excretion of reduced (GSH) and oxidized glutathione. Because the biliary excretion of cysteinylglycine (Cys-Gly), Cys-Gly disulfide, cysteine (Cys) and cystine concomitantly decreased (63-99%), the biliary excretion rate of total glutathione-derived thiols and disulfides did not change. In contrast, acivicin treatment dramatically elevated the urinary excretion rate of glutathione-derived thiols in a dose-dependent fashion, resulting in a 390 fold increase at the highest dosage. This mainly originated from enhancement of urinary excretion of GSH (up to 7200-fold), although the excretion of Cys and Cys Gly into urine was also increased. Acivicin treatment did not affect hepatic and renal levels of GSH but, at high dosages, reduced the concentration of Cys in these organs. GSH and oxidized glutathione concentrations in serum were increased, whereas cystine was diminished in acivicin-treated rats. Inhibition of GGT by acivicin (100 mumol/kg i.v.) failed to influence the biliary excretion of methylmercury but increased urinary excretion 34-fold. Even though the urinary thiol excretion was much higher than the biliary thiol excretion in the acivicin treated rats, methylmercury was preferentially excreted into bile rather than urine, indicating the importance of the liver as an excretory organ for methylmercury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886638 TI - D-1 receptor-linked mechanism modulates cholinergic neurotransmission in rat striatum. AB - SCH 23390, a D-1 dopaminergic antagonist, was examined for its effects on the cholinergic system in rat brain. The compound raised the content of acetylcholine selectively in striatum and not in other brain areas including the hippocampus, nucleus accumbens, hemispheric residuum and midbrain-hindbrain, mirroring the action of dopaminomimetic drugs. That the increase in acetylcholine content reflected a depression of striatal cholinergic neuronal activity was substantiated by the drug's ability to inhibit sodium-dependent high affinity choline uptake, to reduce the electrically evoked release of [3H]acetylcholine from striatal slices in vitro and to reduce acetylcholine release from striatum in freely moving rats in vivo. The increase in striatal acetylcholine was prevented by the D-1 dopaminergic agonist, SK 38393-A, but not by the D-2 agonist, LY 171555. Inhibition of dopamine synthesis by DL alpha-methyltyrosine methyl ester HCI or the selective degeneration of nigrostriatal dopaminergic terminals by the neurotoxin 6-hydroxydopamine HBr prevented the acetylcholine increasing effect of SCH 23390 completely, suggesting that presynaptic dopamine is important in the action of the dopaminergic antagonist. In agreement with these findings, SCH 23390 amplified the action of amphetamine, a dopamine releaser, on striatal cholinergic neurons. Furthermore, blockade of D-2 receptors by pimozide or sulpiride did not suppress the cholinergic effect of SCH 23390. When combined with a subthreshold dose of LY 171555, SCH 23390 did not potentiate the action of the D-2 dopaminergic agonist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886639 TI - Antidotal use of methemoglobin forming cyanide antagonists in concurrent carbon monoxide/cyanide intoxication. AB - An estimated 35% of all fire victims in the United States have toxicologically significant blood levels of CO and CN. However, the treatment of concurrent CO/CN intoxication has been paid scant attention. The suggestion has been made that these victims should be treated for CN poisoning. The current therapeutic management of CN poisoning in this country includes the utilization of two methemoglobin formers: amyl nitrite and sodium nitrite. This study was undertaken to determine if the administration of methemoglobin formers is advisable, as the victim is already suffering from O2 deprivation due to the presence of carboxyhemoglobin. Groups of 28 male ICR mice (22-24 g) were injected i.p. with 5.0 mg/kg of KCN and then were exposed immediately to 0.35% CO for 8.5 min in a dynamic inhalation chamber. Half of the animals were marked randomly for antidotal intervention, the other 14 animals acted as controls. Treatment of survivors with amyl nitrite (12 mg/l of chamber air) for 1 min increased mortality 43%, whereas treatment for 2 min resulted in a 59% increase in mortality. A 25% increase in mortality was noted among those animals treated with sodium nitrite (80 mg/kg i.p.), as compared to the nontreated control survivors. Treatment with dimethylaminophenol (49 mg/kg i.p.) did not statistically affect mortality. PMID- 2886640 TI - Effects of beta-2 agonist on metabolic regulation in the fetal lamb lung. AB - To study the effects of beta-2 agonist on metabolic regulation in fetal lamb lung, ritodrine hydrochloride, a preferential beta-2 agonist, was infused i.v. at a rate of 1.3 +/- 0.4 micrograms/kg/min (mean +/- S.D.) for 24 hr into six twin chronically catheterized fetal lambs starting between 0.86 and 0.91 gestation. Lung glycogen was depleted 56% in the ritodrine-infused twins and glycogen phosphorylase a activity was increased 1.8-fold whereas glycogen synthase activity remained unchanged. Cyclic AMP-dependent protein kinase activity increased 1.7-fold, calcium-calmodulin-dependent protein kinase (phosphorylase kinase) activity increased 1.4-fold and calcium-phospholipid-dependent protein kinase (protein kinase C) activity increased 1.6-fold. In addition, the maximal binding capacity of pulmonary beta receptors decreased 49% in the ritodrine infused twins. However, lung cyclic AMP content was unchanged after 24 hr of ritodrine infusion. We conclude that beta-2 agonist activates protein kinases, depletes glycogen and reduces the binding capacity of beta receptors in the fetal lamb lung. We speculate that these adrenergic mechanisms are involved in regulating the effects of beta-2 agonist on fetal lung liquid and surfactant production. PMID- 2886641 TI - Effects of beta-2 agonist on tracheal fluid flow, surfactant and pulmonary mechanics in the fetal lamb. AB - To study the effects of beta-2 agonist on tracheal fluid, surfactant and pulmonary mechanics in fetal lamb lung, ritodrine hydrochloride, a preferential beta-2 agonist, was infused i.v. at a rate of 1.3 +/- 0.4 micrograms/kg/min (mean +/- S.D.) for 24 hr into six twin chronically catheterized fetal lambs starting between 0.86 and 0.91 gestation. Ritodrine infusion was associated with statistically significant metabolic and pulmonary effects in comparison with twin controls. Fetal serum glucose levels were elevated 1.7-fold, arterial blood pH fell 0.04 U and arterial blood pO2 fell 5.1 torr in the ritodrine-infused twins. Tracheal fluid flow was reduced 6.9-fold and surface active material flux into the tracheal fluid was thereby virtually eliminated. But the surface active material content of tracheal fluid and lung lavage increased 3.0-fold. The surfactant phospholipid content of lung lavage also increased 3.0-fold with no change in its composition. There was a concomitant improvement in pulmonary mechanics on pressure-volume curves: the lungs of the ritodrine-infused twins filled with 1.7-fold more air on inflation to 40 cm of water pressure and also retained 1.7-fold more air on deflation to 10 cm of water pressure. We conclude that beta-2 agonist inhibits tracheal fluid flow, increases surfactant in lung lavage and improves lung stability in the fetal lamb lung. We speculate that preferential beta-2 adrenergic stimulation of the fetal lung with ritodrine could be helpful in the prevention of neonatal respiratory distress syndrome because of enhanced surfactant availability in airways and improved pulmonary mechanics. PMID- 2886642 TI - Effects of ORF 17583, other histamine H2-receptor antagonists and omeprazole on gastric acid secretory states in rats and dogs. AB - ORF 17583, a histamine H2-receptor antagonist, inhibited gastric acid secretion in pylorus-ligated rats (ED50 = 4.9 mg/kg intraduodenal; 3.4 mg/kg p.o.; and 0.21 mg/kg i.p.) and in total gastric fistula or Heidenhain pouch dogs stimulated by betazole (ED50 = 0.12 mg/kg p.o. and 0.08 mg/kg i.v.), histamine, tetragastrin, bethanechol, 2-deoxy-D-glucose or a meal (ED50 values ranged from 0.11-0.26 mg/kg p.o.). The nonspecific inhibition of gastric acid by ORF 17583 supports the existence of interdependence between histamine and the gastrin and cholinergic receptors on the parietal cell surface. Antisecretory potency of ORF 17583 after intraduodenal administration in pylorus-ligated rats was 6.4 times greater than cimetidine, 1.8 times greater than ranitidine, equal to that of omeprazole and 8 times less than that of famotidine. Oral antisecretory potency of ORF 17583 in gastric fistula dogs was 31 times greater than cimetidine, 3.7 times greater than ranitidine and equal to that of omeprazole and famotidine. Studies using equieffective antisecretory doses of ORF 17583 and ranitidine in dogs suggested that ORF 17583 has a short duration of antisecretory activity similar to that of ranitidine. PMID- 2886643 TI - Effects of cocaine on methamphetamine-induced neurochemical changes: characterization of cocaine as a monoamine uptake blocker. AB - Many of the rewarding aspects of cocaine are thought to be due to the ability of this stimulant to block reuptake of monoamines. However, because of its ability also to cause transmitter release, it is difficult to examine the properties of cocaine as an uptake blocker using in vitro techniques such as tissue slices or synaptosomes. Thus, we have evaluated cocaine as a blocker of dopamine and 5 hydroxytryptamine uptake processes by determining the in vivo effect of concurrent administrations of cocaine on the neurochemical effects of methamphetamine treatments. These findings demonstrated that cocaine like 5 hydroxytryptamine uptake blockers such as citalopram, greatly attenuated or blocked decreases in striatal and cortical tryptophan hydroxylase activities and concentrations of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid induced by multiple and single methamphetamine administrations. In contrast to other dopamine uptake blockers, such as amfonelic acid, cocaine did not attenuate the methamphetamine effects on striatal tyrosine hydroxylase activity and the concentrations of dopamine, dihydroxyphenylacetic acid and homovanillic acid. The neurochemical findings were correlated with behavioral analyses. PMID- 2886644 TI - Comparison of the effects of the novel inotropic agent, ibopamine, with epinine, dopamine and fenoldopam on renal vascular dopamine receptors in the anesthetized dog. AB - The effect of i.v. administration of the novel, p.o. active inotropic prodrug, ibopamine, on canine renal vascular dopamine DA-1 receptors was determined in the anesthetized dog. These effects were compared with those produced by the active form of ibopamine, epinine, and with the standard DA-1 receptor agonists, dopamine and fenoldopam. After pretreatment of pentobarbital-anesthetized dogs with phenoxybenzamine (10 mg/kg i.v.) and propranolol (2 mg/kg i.v.) to block alpha and beta adrenoceptor-mediated effects, respectively, the renal blood flow responses to i.v. administration of ibopamine, epinine, dopamine and fenoldopam were determined before and after selective blockade of DA-1 receptors by i.v. infusion of SK&F R-83566 (0.5 microgram/kg/min). Under control conditions, ibopamine produced a dose-dependent increase in renal blood flow as a result of renal vasodilation (i.e., decrease in renal vascular resistance), and was approximately 10-fold less potent than epinine in this respect. Epinine elicited qualitatively similar renal hemodynamic changes to ibopamine with the exception of potency. Dopamine was approximately equipotent with epinine as a renal vasodilator, and both compounds were 10-fold less potent than fenoldopam. Concurrent with the renal vasodilation produced by all four compounds, there was a reduction in mean arterial blood pressure and total peripheral vascular resistance. After the administration of SK&F R-83566, the renal vasodilator responses to fenoldopam were antagonized markedly with an approximate 30-fold rightward shift in the log dose-response curve, whereas the renal vasodilator responses to dopamine were abolished completely and converted into small vasoconstrictor responses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886645 TI - Effects of clenbuterol and prenalterol on behavior maintained under a multiple fixed-interval, fixed-ratio schedule. AB - The results of a number of studies have implicated beta adrenergic receptors in the brain in the actions of proven antidepressant drugs. This suspected involvement of central beta adrenergic receptors made it of interest to characterize the behavioral effects of centrally acting beta adrenergic agonists. Clenbuterol and prenalterol, unlike most beta adrenergic agonists, penetrate into the central nervous system after peripheral administration. In the present study, the effects of these agonists on behavior maintained under a multiple fixed interval 5-min, fixed-ratio 30-response schedule were determined. Both compounds, in a dose-dependent manner, reduced response rate under both components of the multiple schedule. Under the fixed-interval component, clenbuterol and prenalterol altered the temporal pattern of responding. At no dose tested was there evidence for any stimulant action of either of the drugs. The effects of clenbuterol and prenalterol on behavior maintained under the multiple schedule appeared to be a result of an interaction of the agonists with beta adrenergic receptors. This was evidenced by the ability of the beta adrenergic antagonist propranolol to block the effects of the agonists. The behavioral effects of clenbuterol and prenalterol appear, in general, to be similar to effects reported previously for tricyclic and monoamine oxidase inhibiting antidepressant drugs. PMID- 2886646 TI - Characterization of the H2 receptor antagonist and gastric acid antisecretory properties of Wy-45,727. AB - Wy-45,727, structurally similar to ranitidine, was characterized in various models to define its gastric acid antisecretory potency and mechanism of action. In vitro it antagonized the histamine-induced 1) positive chronotropism in isolated guinea pig right atria (pA2 = 8.23, Schild coefficient +/- S.E.M. = 1.09 +/- 0.01), and 2) [14C]aminopyrine uptake in rat isolated gastric mucosal cells. It inhibited acid secretion in dogs (p.o.) prepared with innervated gastric pouches (ED50 = 0.2 mg/kg) and in the pylorus-ligated rat (ED50 = 0.43 mg/kg). ED50 values for ranitidine were 0.9 mg/kg (dog) and 9.97 mg/kg (rat). After an 18 hr pretreatment period with doses up to 300 mg/kg p.o., inhibition of acid secretion in the rat barely exceeded 50%, indicating that the duration of action of Wy-45,727 was not excessive. Wy-45,727 appears to be a selective histamine H2 receptor antagonist. PMID- 2886647 TI - Characterization of vasopressor response to sympathetic stimulation in the pithed rat: differential regulation of neuronally stimulated and blood-borne catecholamine-stimulated pressor responses in rats harboring pheochromocytoma. AB - The vasopressor response to sympathetic stimulation in the pithed rat was characterized both by analyzing the effects of chemical sympathectomy, adrenalectomy and selective antagonists on the vasopressor response and by measurement of changes in plasma concentrations of catecholamines. Stimulation of the spinal sympathetic outflow evoked a biphasic pressor response: an initial transient component was caused mainly by postganglionic sympathetic nerve stimulation (the direct response); a slowly developing secondary component was mediated predominantly by circulating catecholamines released from the adrenal medulla (the adrenal response). Parallel analysis of plasma catecholamines showed that the rise in epinephrine appeared to be closely related to this adrenal component. The pressor response in adrenalectomized rats was selectively blocked by prazosin but not by yohimbine; however, in sympathectomized rats, the pressor response was abolished by prazosin and yohimbine together but not by either drug given alone. These results suggest that the direct, neurogenic component is mediated mainly by alpha-1 adrenoceptors whereas the secondary, adrenally mediated response occurs by activation of both alpha-1 and alpha-2 adrenoceptors. Furthermore, the in vivo regulation of each component of the pressor response was studied in rats harboring pheochromocytoma (PHEO), a tumor causing marked elevations in endogenous catecholamine concentrations. In PHEO rats, the direct pressor response was found to be relatively intact but the adrenal response was blunted. Inasmuch as there was normal rise in plasma epinephrine to electrical stimulation in PHEO rats, the results suggest a differential regulation of neuronally stimulated and blood-borne catecholamine-mediated pressor responses in PHEO rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886649 TI - Local and neurally mediated effects of sufentanil on canine skeletal muscle vascular resistance. AB - The present study examines both the local and neurally mediated effects of sufentanil, a new synthetic opioid, on the vascular resistance of the isolated, separately perfused canine gracilis muscle. Infusions (50 micrograms/min) of sufentanil into the gracilis arteries of nine denervated gracilis muscles did not produce a direct vascular effect. Because morphine has been previously shown to produce a central sympatholytic effect, the neural effect of sufentanil was examined in 12 innervated muscles under conditions of either low or high background sympathetic activity produced by either hemorrhage or transfusion of the dog. After i.v. sufentanil (20 micrograms/kg), all dogs experienced a rapid parallel fall in gracilis vascular resistance (GVR) and mean arterial pressure. The GVR decreased under conditions of high and low sympathetic activity. With low sympathetic tone, the GVR decreased from a control value of 24.1 +/- 4.4 S.E.M. to 6.6 +/- 0.8 resistance units (RU), a value below the subsequently denervated level (13.2 +/- 2.5 RU) (P less than .05). In hemorrhaged animals with elevated control sympathetic tone, resistance declined from 38.4 +/- 9.1 to 26.1 +/- 4.4 RU (P less than .05) but did not reach the denervated level (12.4 +/- 2.7 RU). Local intra-arterial pharmacologic blockade of the gracilis muscle was performed in animals with low sympathetic tone. Intra-arterial atropine did not effect the neurogenic vasodilatory response to sufentanil, whereas prazosin abolished it. Intra-arterial H1 and H2 receptor blockade prevented the decline of GVR secondary to sufentanil below the denervated level. Thus, vasodilation associated with sufentanil administration is mediated solely through neurogenic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886648 TI - Taxol is converted to 7-epitaxol, a biologically active isomer, in cell culture medium. AB - The hydrolysis products of taxol have been isolated by high-performance liquid chromatography and identified by nuclear magnetic resonance and mass spectroscopy. In contrast to taxol, the major hydrolysis product, baccatin III, has little cytotoxic activity and does not promote in vitro microtubule assembly. In cell culture medium, the concentration of taxol decreases with time and 7 epitaxol, which exhibits properties comparable to those of taxol both on cells and on in vitro microtubuli polymerization, is formed. Baccatin III is found in small quantities in the cell medium, although it is barely detectable within the cells. It is concluded that 7-epitaxol is the major derivative of taxol found in cells and that its presence does not alter, in a major way, the overall biological activity of taxol. PMID- 2886650 TI - Selective regulation of beta-2 adrenergic receptors by the chronic administration of the lipophilic beta adrenergic receptor agonist clenbuterol: an autoradiographic study. AB - Many antidepressant drugs, when administered chronically to rats, have been shown to produce decreases in the density of beta adrenergic receptors in the central nervous system. The centrally active beta adrenergic receptor agonist clenbuterol is currently being evaluated clinically as an antidepressant. The chronic administration of this drug to rats resulted in a large decrease in the density of beta adrenergic receptors in some areas of the rat brain but not in others. Thus, autoradiographic studies revealed that the total density of beta adrenergic receptors in the molecular layer of the cerebellum, but not in layers 1 to 3 or layer 4 of the cerebral cortex, was decreased. To examine whether this regional selectivity occurred because of differences in plasticity of cerebellum and cortex or because cerebellum contains mainly beta-2 adrenergic receptors and cortex contains mainly beta-1 adrenergic receptors, separate analyses of the subtypes of beta adrenergic receptors were performed in each area. These experiments indicated that the decrease in receptor density was entirely specific for beta-2 adrenergic receptors, whereas the density of beta-1 receptors was unchanged. Thus, even in layers 1 to 3 and layer 4 of the cerebral cortex, beta-2 receptor density was decreased, with no change in beta-1 receptor density. Using the autoradiographic assay for ligand binding, it was shown that clenbuterol has equal affinity for beta-1 and beta-2 adrenergic receptors, indicating that the selective effect of this drug was not due to a selective affinity for beta-2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886651 TI - Antagonism of cocaine-induced hepatotoxicity by the alpha adrenergic antagonists phentolamine and yohimbine. AB - The ability of the alpha adrenoreceptor antagonists phentolamine and yohimbine to antagonize cocaine-induced hepatotoxicity was determined in phenobarbital-induced B6C3/F1 mice. Hepatotoxicity was assessed by the histologic extent of necrosis, incidence of latent lethality and increases in serum alanine aminotransferase activity. The depression of hepatic glutathione levels also were measured. The administration of a single 5-mg/kg dose of phentolamine antagonized the decrease in glutathione levels and the elevation of aminotransferase activity caused by a 60-mg/kg dose of cocaine. Similar results were obtained in mice pretreated with the alpha-2 antagonist yohimbine. Whereas the duration of antagonism could be extended by administering a 30-mg/kg dose of yohimbine, the magnitude of the antagonism was not increased. In contrast to the experiments with the larger dose, multiple hourly doses of 2.5 mg/kg of yohimbine increased both the duration of antagonism and the magnitude of protection against the hepatotoxicity produced by cocaine. Yohimbine pretreatment reduced cocaine-induced latent lethality by 50%, but did not alter the time to lethality. The results of these experiments indicate that the alpha adrenoreceptor antagonist reduces the toxicity of cocaine rather than merely delaying its time of onset. This effect does not appear to result from an inhibition of the toxic metabolite(s) of cocaine, as a 10-fold molar excess of yohimbine failed to antagonize lipid peroxidation caused by in vitro incubation of cocaine with hepatic microsomes. Additional experiments in mice whose liver metabolism had not been induced by prior pretreatment with phenobarbital revealed that 60 mg/kg of cocaine lowered glutathione but was not hepatotoxic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886652 TI - Nephrotoxicity of S-(2-chloroethyl)glutathione in the Fischer rat: evidence for gamma-glutamyltranspeptidase-independent uptake by the kidney. AB - S-(2-chloroethyl)glutathione (CEG; 270 mumol/kg) produced renal lesions that were confined to the proximal tubules of the outer stripe of the outer medulla and were similar to those lesions produced by the cysteine analog S-(2 chloroethyl)cysteine or by the nephrotoxic glutathione (GSH) adduct of 2 bromohydroquinone. These histopathologic changes in the kidney were correlated with alterations in renal function as reflected by dose- and time-dependent elevations in blood urea nitrogen levels as well as by the increased urinary excretion of protein, glucose and lactate dehydrogenase activity. The role of renal GSH metabolism as a mediating factor in the nephrotoxicity of these GSH conjugates was investigated by administering the gamma-glutamyltranspeptidase inhibitor AT-125 [L-(alpha-S,5S)-alpha-amino-3-chloro-4,5-dihydro-5 isoxazoleacetic acid]. Treatment with AT-125 led to a dose-dependent decrease in renal gamma-glutamyltranspeptidase activity that correlated inversely with increased GSH concentrations in the urine and kidney. Pretreatment with AT-125 ameliorated 2-bromohydroguinone-induced renal toxicity but did not protect against the CEG-induced renal lesion. In fact, pretreatment with AT-125 produced a dose-dependent potentiation of CEG renal toxicity. The CEG-induced renal lesion was dependent on a probenecid-sensitive transport system that was not involved in the toxicity of 2-bromohydroguinone. These studies demonstrate that CEG need not be metabolized by gamma-glutamyltranspeptidase to the corresponding cysteine adduct [S-(2-chloroethyl)cysteine] in order to enter renal tubule cells and ultimately exert its nephrotoxic action. PMID- 2886653 TI - Involvement of N-methyl-D-aspartate receptors in epileptiform bursting in the rat hippocampal slice. AB - The effects of the N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5 phosphonovaleric acid (D-APV), and other excitatory amino acid antagonists, were studied on CA1 pyramidal neurones treated with picrotoxin or bicuculline to reduce synaptic inhibition mediated by gamma-aminobutyric acid (GABA). Under these conditions epileptiform burst firing is readily produced by orthodromic stimulation of the pyramidal cell population. D-APV reduced the plateau amplitude and duration of the depolarization underlying evoked and spontaneous bursts without affecting membrane potential, input resistance or the ability of the cell to fire a Ca2+ spike or a short train of Na+ spikes. A late component of the subthreshold excitatory post-synaptic potential (e.p.s.p.) was voltage dependent, being reduced in amplitude on membrane hyperpolarization. D-APV selectively removed this component of the e.p.s.p. in disinhibited slices. In contrast, in the absence of GABA antagonists, D-APV had no noticeable effect on the e.p.s.p. as studied with field potential recordings. The concentration-response relationship of the inhibitory effect of D-APV and L-APV on population spike bursts was studied. The action of APV was highly stereoselective; the EC50 of D APV was approximately 700 nM, whereas a similar inhibition required 540 microM-L APV. A number of other excitatory amino acid antagonists were tested at a fixed concentration (100 microM). Among them, the quisqualate antagonist gamma-D glutamylaminomethyl sulphonic acid was ineffective against epileptiform bursts. In the low nanomolar concentration range both D- and L-APV potentiated bursting. These results suggest that in the absence of GABAergic inhibition, a significant component of the slow depolarization underlying burst firing is voltage dependent, synaptic in origin and mediated by NMDA receptors. We propose that, under normal (non-epileptic) physiological conditions, the balance between synaptic inhibition mediated by GABA receptors and synaptic excitation mediated by NMDA receptors may modulate the excitability of pyramidal cell dendrites. PMID- 2886655 TI - The effect of adrenergic, cholinergic and peptidergic salivary stimulants on gastric mucosal integrity in the rat. AB - Sialoadenectomized and sham-operated rats were given salivary secretory stimulants 30 min prior to intragastric instillation of a bile salt solution (5 mM-sodium taurocholate in 100 mM-HCl). Administration of the alpha-agonist phenylephrine (0.15-15 mg/kg) resulted in a dose-dependent reduction in the loss of H+ and the intraluminal appearance of Na+ and K+ associated with bile-salt induced damage to the stomach in the sham-sialoadenectomized rat. The effect was not apparent if the salivary glands had been previously excised. Adrenaline (0.8 4.0 mg/kg) and noradrenaline (0.8-4.0 mg/kg) were less effective in reducing the degree of mucosal damage in sham-sialoadenectomized rats and were not effective in sialoadenectomized rats. Administration of secretory stimulant doses of isoprenaline (5 mg/kg), pilocarpine (2 mg/kg) and substance P (25 mg/kg) either had no significant effect or exacerbated the net transmucosal fluxes of H+, Na+ and K+ associated with bile salt damage to the gastric mucosa. The protective action of phenylephrine in sham-sialoadenectomized rats was reversed by prior treatment with the alpha-antagonist, phentolamine (2 mg/kg). The effect of phentolamine was dose dependent. Vagotomy abolished the protective influence of phenylephrine in sham-sialoadenectomized rats but did not influence the response to other salivary secretory stimulants consistently. These data suggest that stimulation of alpha-adrenergic receptors in rat salivary tissue is associated with an amelioration of the increase in gastric mucosal permeability to H+, Na+ and K+ in response to an intraluminal bile salt solution. The apparent protective influence of alpha-adrenergic receptor activation in sham-sialoadenectomized rats is mediated in part by the vagus nerve. PMID- 2886656 TI - The effects of electrical stimulation of myelinated and non-myelinated vagal fibres on heart rate in the rabbit. AB - The bradycardia evoked by electrical stimulation of the peripheral end of the rabbit vagus nerve is mediated by both myelinated and non-myelinated fibres. Stimulation of myelinated fibres at 5 Hz for 20 s resulted in a fall in heart rate from a control value of 204 +/- 1.3 to 182 +/- 1.2 beats min-1 (means + S.E. of means). On stimulation of both myelinated and non-myelinated fibres, heart rate fell to 169 +/- 2.1 beats min-1. Heart rate returned rapidly to control value following stimulation of myelinated fibres but only slowly after stimulation of both myelinated and non-myelinated fibres. Thus recruitment of non myelinated fibres increased both the magnitude and duration of the bradycardia. Atropine abolished all effects of vagal stimulation on heart rate. Hexamethonium abolished the effect of myelinated fibres on heart rate; however, recruitment of non-myelinated fibres still produced a bradycardia. It is suggested that the prolonged effect following stimulation of non-myelinated fibres may reflect the persistent action of a non-cholinergic excitatory transmitter at the ganglion. PMID- 2886654 TI - Motoneurones of the submucous plexus regulate electrical activity of the circular muscle of canine proximal colon. AB - The hypothesis that the circular muscle of the canine proximal colon receives motor input from neurones in the submucous plexus was tested. Circular muscle cells were impaled with micro-electrodes and submucous plexus neurones were stimulated by electrical field stimulation and microejection of acetylcholine (ACh). In the presence of atropine to block the direct muscarinic effects, microejection of ACh onto the submucosa where intact submucous ganglia were suspended evoked: (i) an inhibitory junction potential (i.j.p.) that reduced the amplitude, duration and rate of rise of the subsequent slow wave; (ii) a slow wave of increased duration following the initial inhibitory response. These responses were enhanced by increasing the volume of ACh administered. Responses to ACh were blocked by hexamethonium, 10(-4) M; d-tubocurarine, 10(-4) M; or tetrodotoxin (TTX), 10(-6) M, suggesting they were neural in origin. Both inhibitory and excitatory responses were the result of non-cholinergic and non adrenergic nerves. The transmitters mediating these effects are unknown. Removal of the longitudinal muscle, myenteric plexus, and the serosal portion of the circular muscle had no apparent effect on the responses to application of ACh to submucosal ganglia. In these preparations the responses to field stimulation were identical to those produced by ACh. The submucous plexus also provides cholinergic input to the circular muscle. When ACh was discretely applied to the submucosa cholinergic responses were elicited at the muscle cell which were significantly reduced by hexamethonium or TTX. These findings suggest that the cholinergic responses were the result of ACh release by neurones at the effector and not by overflow of the exogenous ACh. Cholinergic responses were also elicited in preparations in which the myenteric plexus had been removed. Slow waves in circular muscle of the proximal colon yield excitation-contraction coupling in the absence of Ca2+ action potentials. Therefore the influence of submucous neurones on electrical slow waves has direct consequences on motor activity. Reduction in the amplitude and duration of slow wave by i.j.p.s. results in reduction in the amplitude and duration of phasic contractions. Excitatory inputs enhance contractions. The data support a new concept: motoneurones emanating from submucous ganglia innervate the circular muscle and provide inhibitory and excitatory inputs to regulate slow wave activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2886657 TI - Tensile strengths and microscopic analysis of nickel-chromium base metal postceramic solder joints. PMID- 2886658 TI - Withdrawal syndromes. PMID- 2886660 TI - Complement activation and vascular injury in systemic lupus erythematosus. AB - The deposition of immune complexes within blood vessel walls results in the potential for complement activation and the release of chemotactic factors, such as fragments of C5 (C5fr). The generation of C5fr results in the intravascular aggregation of neutrophils with subsequent leukostatic occlusion of the pulmonary arterioles. The generation of C5fr may contribute to the pathogenesis of adult respiratory distress syndrome and other diseases. Studies were undertaken to determine the role of circulating complement derived peptides and intravascular neutrophil activation in systemic lupus erythematosus. PMID- 2886659 TI - Basic elements of murine systemic lupus erythematosus. AB - Knowledge about murine lupus and by analogy human lupus, has increased much in recent decades. Relatively complete descriptions of the development of this disease, particularly at the cellular, humoral, and in some cases the molecular level, are now available, but why the disease occurs is still unknown. Technologies designed to describe cellular and humoral immunologic events in progress and ways to artificially induce such abnormalities are described. However, until recently techniques capable of defining the genes determining immunologic function or revealing abnormalities of these genes which might predispose to diseases such as lupus were unknown. Since the disease itself can apparently be caused in genetically dissimilar individuals by different pathogenic mechanisms, and since most of the individual autoimmune traits appear to be multigenic, the lupus prone genetic backgrounds will be complex. The pertinent genetic elements in disease prone animals are examined and compared. PMID- 2886661 TI - PCNA/cyclin: a lupus antigen connected with DNA replication. AB - Molecular analysis of the proliferating cell nuclear antigen (PCNA) has the 2 fold goal of utilizing the unique tools provided by autoimmune sera to study the function of this important intracellular molecule and to provide insights into the etiology of autoimmune disease. PCNA is expressed in the nucleus immediately preceding S phase and, during S phase is colocalized with sites of active DNA synthesis. There is currently available not only a battery of human sera which can be rendered monospecific for PCNA, but also monoclonal antibodies and rabbit antipeptide antibodies. With these reagents, it might be possible to isolate cDNA clones from cDNA expression libraries. PMID- 2886662 TI - [Pulpy kidney in the lamb]. PMID- 2886663 TI - Synthesis, conformation, and dopaminergic activity of 5,6-ethano-bridged derivatives of selective dopaminergic 3-benzazepines. AB - To probe the suggestion that D-1 (DA1) dopamine receptors might possess an accessory pi-binding site in a location complementary to a suitably oriented aromatic ring (i.e., in an axial orientation approximately orthogonal to the catechol nucleus) in agonists such as 2,3,4,5-tetrahydro-1-phenyl-1H-3 benzazepine-7,8-diol (1) and 3',4'-dihydroxynomifensine (2) that are selective for this subtype, cis- and trans-2,3,4,8,9,9a-hexahydro-4-phenyl-1H-indeno[1,7 cd]azepine-6,7-diol were prepared. These compounds are 5,6-ethano-bridged derivatives of the D-1 selective dopamine receptor agonist 1. Introduction of the bridge reduces the conformational mobility of the parent molecule. Comprehensive conformational analyses by molecular mechanical methods indicated that both the cis and trans isomers could attain a conformation that places the phenyl substituent in an axial orientation. X-ray analysis of the trans isomer showed an axial disposition of the phenyl ring; however, NMR studies suggest that this conformation is fixed in the trans isomer, but not in the cis. The dopamine receptor binding affinity and intrinsic activity of the cis isomer were considerably greater than those of its trans counterpart; the cis isomer also demonstrated a high degree of selectivity for the D-1 subtypes. One possible explanation of these results, suggested by the molecular modeling studies, is that both the axial orientation of the phenyl postulated to be required for binding to the receptor and a putatively requisite location of the nitrogen in approximately the plane of the catechol ring can be attained only by the cis isomer in which the tetrahydroazepine ring is in a twist conformation. Conversely, these results might simply suggest a preference of the D-1 receptors for benzazepine agonists having the phenyl group in an equatorial orientation. Still another possibility is that the D-1 receptor binding site is in a sterically hindered area accessible only to compounds that are relatively planar. However, it requires an axial 1-phenylbenzazepine for strong binding. Thus, a conformationally flexible cis isomer could more readily achieve the different conformations required to both gain access to and bind with the D-1 site. PMID- 2886664 TI - Berbanes: a new class of selective alpha 2-adrenoceptor antagonists. AB - The alpha-adrenoceptor blocking properties of some berbanes have been studied and compared with those of idazoxan, yohimbine, phentolamine, and prazosin. Their effects on presynaptic alpha 2-adrenoceptors were studied on chemical neurotransmission of isolated rat vas deferens and longitudinal muscle strip of guinea pig ileum; xylazine or norepinephrine was employed as agonist. The alpha 1 adrenoceptor blocking activities of the berbanes were tested on isolated rat vas deferens and rabbit pulmonary artery by using phenylephrine or norepinephrine as agonist. The antagonistic activity of the berbanes and the reference compounds on alpha 2- and alpha 1-adrenoceptors was characterized by the apparent pA2 values. Of the compounds studied, [8aS*-(8a alpha,12a alpha,13a alpha)]-11 alpha-hydroxy 5,6,8a,9,10,11,12a,13,13,a-decahydro-8H-benzo[g]-1,3 -benzodioxolo[5,6-a]quinoli zine, 6d, proved to be the most selective antagonist at the presynaptic alpha 2 adrenoceptors (alpha 1:alpha 2 ratio = 1659). Since blockade of alpha 2 adrenoceptors located on noradrenergic axon terminals leads to an increase of norepinephrine release, this compound could have potential as an antidepressant agent. PMID- 2886665 TI - The HLA linked iron loading gene in an Afrikaner population. AB - The serum ferritin concentration was used as a screening test to identify the presence of iron overload in 599 Afrikaans subjects (300 males and 299 females) living in the South Western Cape, South Africa. Seventeen of the males with concentrations greater than 400 micrograms/l were reevaluated three and five years later. Serum ferritin concentrations were measured again and further diagnostic procedures were carried out. These included an assessment of alcohol intake and measurements of serum gamma glutamyltransferase, the percentage saturation of transferrin, and HLA-A,-B,-C, and -DR loci typing on the subjects as well as their families. Liver biopsies were performed on some affected subjects. Of the original 16 index subjects, four were diagnosed as homozygous for the HLA linked iron loading gene which is responsible for the clinical disease idiopathic haemochromatosis. Six appeared to be heterozygotes, three were heterozygotes who were also abusing alcohol, and two did not fit into any of the diagnostic groups. The calculated gene frequency was 0.082, with an expected heterozygote frequency of 0.148. The fact that no females were identified in the study suggested that the diagnostic criteria for homozygosity (serum ferritin greater than 400 micrograms/l and % saturation greater than 60%) were set too high. The data were therefore recalculated for the 300 males; when this was done the gene frequency was 0.115 and the heterozygote frequency 0.024. Two subjects were diagnosed as homozygotes in the study of family members and 37 as heterozygotes (33 definite and four probable). Both the homozygotes and nine of the heterozygotes showed mild to moderate disturbances of iron metabolism. There was considerable overlap between the phenotype expression in these nine heterozygotes and the homozygotes, probably as a result of setting the threshold for the serum ferritin concentrations at the relatively high value of 400 microgram/ml. By doing this a small subset of heterozygotes with biochemical abnormalities was identified. The results of the present pilot study suggest a high frequency of the HLA linked iron loading gene in the Afrikaner population of South Western Cape. PMID- 2886668 TI - Antigenic relationships among type-1 fimbriae of Enterobacteriaceae revealed by immuno-electronmicroscopy. AB - Antigenic relationships among type-1 fimbriae of 40 strains of Enterobacteriaceae representing 19 species and seven genera were determined by immuno electronmicroscopy. Ten distinct antigenic groups were distinguished. Intra- and inter-generic relationships were observed although some antigenic groups were species-specific only. Antigenic relationships among type-1 fimbriae are more complex than have been reported hitherto. PMID- 2886666 TI - Prenatal prediction of osteogenesis imperfecta (OI type IV): exclusion of inheritance using a collagen gene probe. AB - Autosomal dominant osteogenesis imperfecta is caused by mutations in the COL1A2 and COL1A1 genes of type I collagen. In a family with OI type IV genetically linked to the COL1A2 gene, we attempted prenatal diagnosis in a pregnancy at risk by genotyping the DNA of the fetus for a COL1A2 gene associated RFLP. Our results showed that the fetus inherited the normal COL1A2 allele from her affected parent. Linkage analysis can thus be used in the prenatal diagnosis of dominantly inherited osteogenesis imperfecta. PMID- 2886669 TI - Sulfasalazine and its metabolites attenuate respiratory burst of leukocytes--a possible mechanism of anti-inflammatory effects. AB - The effects of sulfasalazine and its metabolites, 5-amino salicylic acid and sulfapyridine on respiratory burst of polymorphonuclear leukocytes were investigated by determining not only luminol-dependent chemiluminescence for the detection of myeloperoxidase-mediated active oxidants, but also lucigenin dependent chemiluminescence for the detection of superoxide anion. The present study showed that sulfasalazine, 5-amino salicylic acid and sulfapyridine attenuated active oxygen species from polymorphonuclear leukocytes at the concentrations comparable to clinical doses. Therefore, it was concluded that anti-inflammatory effects of sulfasalazine can be explained by the ability of sulfasalazine and its degraded compounds to scavenge active oxidants from polymorphonuclear leukocytes. PMID- 2886667 TI - The fragile X syndrome in a large family. III. Investigations on linkage of flanking DNA markers with the fragile site Xq27. AB - In a large family with the fragile X syndrome, we performed linkage investigations with six probes, detecting RFLPs at both sides of the fragile site Xq27. The nearest flanking markers were cX55.7 (DXS105) on the centromeric side (theta = 0.04, lod 5.0) and St14 (DXS52) on the telomeric side (theta = 0.08, lod 4.0). Non-penetrance could be shown by the presence of the grandpaternal X chromosome in three mentally retarded fra(X) positive males. A second non penetrant male in this family had inherited an abnormal grandmaternal X chromosome. His carrier mother had two retarded fra(X) positive brothers. Intermediate between the non-penetrant and fully penetrant males was a non retarded male, who expressed the fragile site in 6% of his cells. His X chromosome showed the same polymorphisms as were found in his seven severely retarded brothers. In five fra(X) negative females the presence of an abnormal X chromosome could be demonstrated. Despite the existence of non-penetrance in this pedigree, there was no close linkage between a factor IX polymorphism and the fragile site (theta = 0.16, lod 1.9). However, in six descendants of a non penetrant male, the change to penetrance appeared to be accompanied by a low recombination frequency for flanking markers. PMID- 2886670 TI - A group of repetitive human DNA families that is characterized by extrachromosomal oligomers and restriction-fragment length polymorphism. AB - We have recently reported a novel human repetitive DNA (Sau3A family) that exists both in the chromosomes and in the extrachromosomal fraction. Several more clones that hybridized with the Sau3A family were isolated from the extrachromosomal fraction of HeLa cells. Use of these clones as probes has revealed that at least four different types of oligomeric forms of DNA are present in the extrachromosomal fraction. The oligomers consist of one, two, five or 12 subunits of basic 170 base-pair unit DNA, or superimposed forms of two of them. Nucleotide sequencing of these clones indicated that the clones have 70 to 90% sequence homology with human alphoid satellite DNA. These DNA sequences are present also in the chromosomes, as tandemly repeated DNA sequences, and exhibit a considerable degree of restriction-fragment length polymorphism. These results, taken together with the previous findings on Sau3A family DNA, suggest that there is a group of recombination-prone repetitive DNA families in human chromosomes. PMID- 2886672 TI - Multiple severe complications from recreational ingestion of MDMA ('Ecstasy') PMID- 2886671 TI - 1H nuclear magnetic resonance studies of an integral membrane protein: subunit c of the F1F0 ATP synthase. AB - The membrane-traversing subunit c parallel from the F0 part of the ATP synthase molecule has been studied in chloroform/methanol by high-resolution 1H n.m.r. Various one-dimensional and two-dimensional techniques have been used for assignment purposes, some NOE connectivities were established and some 3JHN alpha coupling constants were measured from spin--echo experiments. The effects of varying pH, solvent composition, lanthanide concentration and temperature have been investigated. Evidence is presented that the molecule has extensive alpha helical segments, and the hairpin structure suggested by other groups is supported by our n.m.r. data. Only one ionizable group, assigned to the C terminal carboxyl, is observed to titrate in the pH range 2 to 10; so the conserved residue, Asp61, which binds dicyclohexylcarbodiimide, presumably has (at least in this solvent system) an abnormally high pK value. PMID- 2886673 TI - [The effects of pancuronium and vecuronium on the norepinephrine dose-response curve in the aortic strip in the cat]. PMID- 2886674 TI - [A double-blind evaluation of famotidine for pre-anesthetic intramuscular administration--its effects on volume and pH of gastric juice]. PMID- 2886675 TI - [A case of ATL presenting a huge intrahepatic tumor, abated with etoposide (NK 171) therapy alone]. PMID- 2886676 TI - [Laser endoscopy: diagnosis and therapy. 8. Laser endoscopy lithotripsy of biliary tract calculi]. PMID- 2886677 TI - [DNA diagnosis of hemophilia B]. PMID- 2886678 TI - [DNA analysis in the diagnosis of hemorrhagic diathesis]. PMID- 2886679 TI - [Morphological studies on cells from adult T cell leukemia. I. Cell morphology and clinical subtypes]. PMID- 2886680 TI - [Morphological studies on cells from adult T cell leukemia. II. Lobulated lymphocytes and HTLV-I infection]. PMID- 2886681 TI - [Detection of anti-human retrovirus antibody]. PMID- 2886682 TI - Apolipoprotein AI-CIII gene polymorphisms in a Japanese population. PMID- 2886683 TI - Assignment of a polymorphic locus of OS-4(D18S5) DNA segment to human chromosome region 18q21.3----qter. PMID- 2886684 TI - Apolipoprotein AI-CIII gene polymorphisms in Japanese myocardial infarction survivors. PMID- 2886685 TI - RFLPs of factor IX gene in Japanese haemophilia B families and gene deletion in two high-responder-inhibitor patients. PMID- 2886686 TI - The zygosity determination of Japanese twins using a minisatellite core probe. PMID- 2886687 TI - Noradrenaline-sensitive cyclic AMP-generating system of rat cerebral cortex with iron-induced epileptiform activity. AB - Noradrenaline-elicited accumulation of cyclic AMP and effects of an alpha-, beta adrenoceptor, or adenosine receptor antagonist on the accumulation were examined in slices of different areas of rat cerebral cortex in which ferrous chloride solution was injected unilaterally into the sensorimotor cortex to induce epileptiform activity. The cyclic AMP accumulation was altered regionally in relation to both lateral dominance of electrographic isolated spike activity and variance of the epileptic process. Involvement of a beta-adrenergic, and possibly alpha-adrenergic, mechanism in the alterations in the cyclic AMP accumulation was indicated. PMID- 2886688 TI - Two kinds of modification by 5-methoxy-N,N-dimethyltryptamine of contractile responses to electrical stimulation of isolated guinea-pig vas deferens. AB - Two kinds of electrical stimulation, low frequency stimulation (5 Hz, 1 msec, 5 pulses, every 20 sec) and high frequency stimulation (30 Hz, 0.1 msec, 20 pulses, every 20 sec), produced contractions in isolated guinea-pig vas deferens. These responses were blocked by alpha, beta-methylene-ATP, but not prazosin. Phentolamine potentiated the contractions produced by low frequency stimulation, while it had little or no effect on the contractions produced by high frequency stimulation. The effect of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), a potent short acting hallucinogen, on the contractile response to two kinds of electrical stimulation was examined. On the contraction produced by low frequency stimulation, 5-MeODMT showed a biphasic action. 5-MeODMT at concentrations of 3 X 10(-8)-10(-6) M reduced the contractile response. 5-MeODMT at concentrations of 3 X 10(-6)-2 X 10(-5) M potentiated the contractile response, and this potentiation was reversed by prazosin and ketanserin. Clonidine caused an inhibition of the contractile response to low frequency stimulation. This action of clonidine was reversed by 5-MeODMT. The reverse action of 5-MeODMT was greatly inhibited in the presence of prazosin and ketanserin. The results suggest that 5-MeODMT exerts two different kinds of modification on the contractile response to low frequency stimulation of isolated guinea-pig vas deferens: in one type of modification, 5 MeODMT at concentrations higher than 3 x 10(-8) M exerts an action similar to that of 5-hydroxytryptamine on postganglionic sympathetic nerve terminals and reduces the release of transmitter presynaptically, and in the other type, 5 MeODMT at concentrations higher than 3 x 10(-6) M causes the release of noradrenaline from postganglionic sympathetic nerve terminals. PMID- 2886689 TI - Effects of DJ-7141, a new peripherally acting alpha-2 adrenoceptor agonist, on blood pressure and gastric acid output in rats: evidence for the heterogeneity of alpha-2 adrenoceptors in different organs. AB - Effects of intravenously administered clonidine and DJ-7141 on blood pressure and gastric acid output were studied in anesthetized rats. Both drugs caused a dose dependent increase in blood pressure. Clonidine-induced increases in the blood pressure were attenuated by yohimbine and prazosin. DJ-7141-induced increases in blood pressure were also attenuated by yohimbine, but were little affected even by a large dose of prazosin. Splanchnic nerve stimulation-induced increases in blood pressure were attenuated by clonidine and DJ-7141. The inhibitory effects of DJ-7141 exceeded those of clonidine. On the other hand, these agonists had no effect on exogenously applied norepinephrine-induced increases in blood pressure. Vagally stimulated gastric acid output was inhibited by small doses of clonidine and large doses of DJ-7141. Clonidine-induced inhibition of acid output was abolished by yohimbine (5 mg/kg), but not by prazosin (5 mg/kg). In contrast, the DJ-7141-induced inhibition of acid output was not affected by yohimbine (5 mg/kg), but was attenuated by a small dose of prazosin (0.1 mg/kg). These results indicate that DJ-7141 had no effect on alpha-2 adrenoceptors in gastric parasympathetic nerves. Furthermore, the alpha-2 adrenoceptors on parasympathetic nerves in the gastric wall are probably pharmacologically different from those on sympathetic nerves and blood vessels in rats. PMID- 2886691 TI - [Inhibitory effect of ticlopidine on platelet aggregation in open heart surgery]. PMID- 2886690 TI - A trial for kinetic evaluation of the antagonistic potency of several beta antagonists on presynaptic beta-adrenoceptors. AB - The antagonistic potency, pA2, of several non-selective beta-antagonists on presynaptic beta-adrenoceptors was evaluated using a parallel line assay and MacKay's equation against isoproterenol-induced increases in 3H release in isolated guinea-pig pulmonary arteries preloaded with 3H-norepinephrine. Cumulatively applied isoproterenol at 10(-9) M, 10(-8) M and 10(-7) M dose dependently increased 3H release evoked by transmural field stimulation at 1 Hz. beta-Antagonists tested dose-dependently antagonized the isoproterenol-induced increases. The order of pA2 was carteolol (11.23 +/- 0.09) greater than nadolol (9.78 +/- 0.05) greater than pindolol (9.59 +/- 0.03) greater than propranolol (9.26 +/- 0.17). Carteolol has the highest pA2 and is a useful tool for clarifying whether or not presynaptic beta-adrenoceptors tonically function. PMID- 2886693 TI - [Gamma-glutamyl transpeptidase activities in human renal tumors]. PMID- 2886692 TI - [Immunological investigation of SSEA-1 antigen and its derivatives in the serum in urological malignancies]. PMID- 2886694 TI - [Peripheral vasodilators in the treatment of chronic cardiac insufficiency]. PMID- 2886695 TI - [Effect of silver preparations on the microflora regenerated from a condensate of atmospheric water vapor in a hermetically-sealed chamber]. AB - The effect of different silver compounds (silver sulphate, silver nitrate, electrolytic ionic silver) on microorganisms in water reclaimed from the atmospheric condensate in an enclosed environment was investigated. The following microorganisms were examined: Alcaligenes faecalis, Citrobacter freundii. Aeromonas hydrophila, Staphylococcus epidermidis, etc. The ionic silver concentrations in solution varied from 0.1 to 10 mg/l. The efficiency of the silver compounds was found to depend on the microbial strain, ionic silver concentration in solution, and time of exposure. The microflora of the reclaimed water proved to be highly resistant to the preservatives which was strongly associated with the bacterial physical and chemical composition of the products preserved. PMID- 2886696 TI - A device for restraining rabbits while bloodfeeding mosquitoes. PMID- 2886697 TI - Disability resulting from underfoot first events. PMID- 2886698 TI - Evaluation of calcium entry blockers and alpha 2-adrenergic antagonists on B-HT 920-induced pressor responses in the autonomically blocked dog. AB - Several calcium entry blockers and alpha 2-adrenergic receptor antagonists were evaluated for inhibition of pressor responses induced by the selective alpha 2 agonist B-HT 920 in pentobarbital-anesthetized dogs pretreated with prazosin (0.5 mg/kg, i.v.), propranolol (0.5 mg/kg, i.v.), and hexamethonium (10 mg/kg i.v.). In this preparation, autonomic blockade (alpha 1, beta, and ganglionic block) persists for approximately 4 hr. The B-HT 920 administered intravenously causes dose-related increases in mean arterial blood pressure (ED50 = 4.90 micrograms/kg, i.v., dose causing a 50 mm Hg rise in mean arterial blood pressure). Maximum increases in mean arterial pressure approximate 80 mm Hg at 100 micrograms/kg, i.v. Repeated bolus administration of B-HT 920 over a 4-hr period shows no significant reduction in the pressor response, suggesting good stability of this experimental model and no rapidly developing tolerance. Calcium entry blockers (nifedipine, D-600, and diltiazem) and alpha 2-adrenergic receptor antagonists (yohimbine and idazoxan) inhibit the B-HT 920-induced pressor response in a dose-related manner. The ED50 values (dose of antagonist that causes a 50% inhibition of B-HT 920-induced pressor response) were calculated. Idazoxan and yohimbine have ED50 values (mg/kg, i.v.) of 0.086 and 0.063, respectively, whereas D-600, nifedipine, and diltiazem have values of 0.074, 0.111, and 0.542, respectively. The data show that calcium entry blockers and alpha 2-adrenergic blockers are potent inhibitors of B-HT 920 pressor responses in the autonomically blocked dog. This experimental model is appropriate for the evaluation of calcium entry blockers and/or alpha 2-adrenergic antagonists in vivo. PMID- 2886700 TI - Takayasu's arteritis with bilateral pulmonary artery stenosis. Successful surgical correction. AB - The case of a 60-year-old patient with severe stenosis of both proximal pulmonary arteries resulting from Takayasu's arteritis is reported. The thoracic aorta and pulmonary artery were calcified. Patch enlargement of the pulmonary arteries was successfully performed. Operative biopsies confirmed the diagnosis of nonspecific arteritis consistent with Takayasu's disease. PMID- 2886699 TI - HWGA reports on: the status of physician assistant's practice in Kentucky. PMID- 2886701 TI - Internal mammary artery grafting. PMID- 2886703 TI - A case of CD4+/CD8- adult T-cell leukemia with good response to interferon-beta terminating as a CD4+/CD8+ adult T-cell lymphoma. AB - The leukemic cells of adult T-cell leukemia (ATL) usually express the helper/inducer associated antigen reactive with anti-CD4 antibodies but not with anti-CD8. We present a 63-yr-old woman with ATL characterized by circulating leukemic cells with CD4+/CD8- phenotype, hepatosplenomegaly with no lymphadenopathy, and the presence of proviral DNA of human T-cell leukemia virus I in the leukemic cells. She was successfully treated with interferon beta and the remission lasted for 12 months. She then relapsed in the lymph nodes with minimal peripheral blood involvement. The neoplastic cells of the lymph node now co-expressed CD4 and CD8 antigens indicating that the change in clinical manifestation was accompanied by a phenotypic change of the leukemic cells. PMID- 2886702 TI - Myeloproliferative disorder due to abnormal production of hematopoietic stimulators. AB - A new kind of myeloproliferative disorder (L-8313) has been discovered. It was transplantable into syngeneic mice with spleen cells. The mice showed hepato splenomegaly with a marked leukocytosis and anemia 3 weeks after transplantation of L-8313 cells. The number of GM-CFU and CFU-S per spleen increased to more than 40 times normal. The results of chromosomal and PGK analysis demonstrated that these increased stem cells were of host origin. Both the culture medium of the spleen cells and the serum from L-8313 bearing mice showed high levels of IL-3, BPA and CSF. Consequently, hematopoietic cells of the host mice underwent remarkable proliferation in response to these stimulating factors when L-8313 cells were transplanted. We also have been successful in establishing an in-vitro cell line and have maintained it for over one year. The phenotype of L-8313 cells was Thy 1.2 positive. Some L-8313 cells showed a positive acid phosphatase reaction but the cytochemical character of myeloid lineage was not observed. Therefore, L-8313 is considered to be a T-cell derived hematopoietic regulatory cell neoplasm with the ability to produce several hematopoietic stimulating factors. PMID- 2886704 TI - Polyarteritis nodosa of the liver--a case report and review of the literature. PMID- 2886705 TI - Stimulative effect of somatostatin on cell proliferation in cultured chondrocytes. AB - We have earlier demonstrated that human growth hormone stimulates DNA synthesis and proteoglycan production in cultured chondrocytes. The present study is concerned with the effects of somatostatin and other neuropeptides on cell proliferation by cultured rat rib growth plate chondrocytes. Chondrocytes were isolated from the growth plates by collagenase digestion and cultured as monolayers in multiwell plates. The cells were allowed to attach overnight and subsequently incubated for 24 h under serum-free conditions to establish growth arrest. Somatostatin and other peptides were then added and the cultures were incubated for 18 h. Finally, the cultures were labelled for 6 h with tritiated thymidine in the presence of peptide. For screening purposes, the effect on DNA synthesis was assayed as incorporation of [3H]-thymidine into acid-insoluble material. For a more exact estimate, parallel cultures were prepared for autoradiography and the fraction of labelled nuclei was determined by counting. Among the peptides we tested (somatostatin, GRF, TRH, SP, mENK, PHI, VIP, hCT) only somatostatin had any discernible effect on DNA synthesis, with an apparently optimal effect at 10 fM. This concentration is well within the range found in various tissues in vivo and suggests a physiological role for somatostatin in chondrocyte growth regulation. Further experiments are required, however, to clarify by which mechanism somatostatin influences the cells and whether the peptide interacts with other growth factors such as the IGFs. PMID- 2886706 TI - Histaminergic mechanisms in the brain. PMID- 2886707 TI - [Detection of alcoholism in the general hospital. Psychometric and biological instruments]. PMID- 2886708 TI - [Multiple endocrine adenomatosis type II-a: presentation of a stricken family]. PMID- 2886710 TI - [Multiple endocrine neoplasms type II]. PMID- 2886711 TI - [Psychiatric manifestations of systemic lupus erythematosus and its prevalence in mental patients]. PMID- 2886713 TI - [Strategy for the control of HIV infection using epidemiological methods]. PMID- 2886712 TI - Inhibition of aconitine-induced mortality in the conscious rat: a screening test for antiarrhythmic drugs. AB - A test for inhibition of mortality induced by intravenous injection of aconitine in rats is proposed as a particularly valid method, owing to its simplicity and degree of specificity, for inclusion among the preliminary screening tests for antiarrhythmic activity. LD50 (63.5 micrograms/kg, i.v.) and LD99 (118.9 micrograms/kg, i.v.) values of aconitine were determined. The dose employed for screening was 100 micrograms/kg i.v., which in control animals produced a death rate of 97.7% (293 deaths/300 treated animals). The protection produced by various drugs belonging to different groups of antiarrhythmics was studied. ED50s, expressed in mg/kg i.p., were as follows: Class I antiarrhythmics: flecainide, 5.5; E-4017, 30.0; lorcainide, 30.9; quinidine, 41.1; diphenylhydantoin, 42.3; lidocaine, 48.5; ajmaline: 53.9; procainamide, 61.3. Class II antiarrhythmics: pindolol 22.8; propranolol, 24.9; oxprenolol, 38.0; labetalol, 60.7; atenolol, 100.0; metoprolol, approximately 160; acebutalol, greater than 160; timolol, greater than 160. Class III antiarrhythmics: amiodarone, greater than 160. Class IV antiarrhythmics: verapamil, diltiazem and nifedipine were inactive up to 40 mg/kg. The test would appear to be selective for membrane-stabilizing agents (class I) and beta-blockers (class II), but in view of the magnitudes of activity found, it should be used in combination with other antiarrhythmic tests. PMID- 2886709 TI - [Multiple endocrine neoplasms (MEN I): experience with 15 cases]. PMID- 2886714 TI - Non-cytocidal natural variants of human immunodeficiency virus isolated from AIDS patients with neurological disorders. AB - To understand the mechanism of HIV-mediated neuropathology five viral isolates were obtained from four AIDS cases with central nervous system manifestations as the primary involvement. The isolates were identified as HIVs by antigenic cross reactivity and nucleic acid hybridizations to HIV-specific antibodies and DNA probes. The replication and cytopathic properties of these isolates were studied and compared with lymphadenopathy-associated virus (HIVLAV). All isolates had replication competence equivalent to LAV, but four isolates did not kill T4 (CD 4) cells. This isolation of non-cytocidal natural variants of HIV raises the possibility that in some AIDS cases the neurological disorders might be due to HIV variants that are non-cytocidal to T4 cells. The results also indicate that virus replication and cytotoxicity are not always concordant functions in HIV. PMID- 2886715 TI - Raised cerebrospinal-fluid copper concentration in Parkinson's disease. AB - The cerebrospinal-fluid copper concentration, measured by electrothermal atomisation/atomic absorption spectrophotometry, was significantly higher in 24 patients with untreated, idiopathic Parkinson's disease than in a control population of 34 patients (p less than 0.001). The difference in the in-vitro capacity of copper to damage DNA, measured by the phenanthroline assay was even greater. The high phenanthroline-copper concentration correlated with disease severity (p = 0.02) and with the rate of progression of disease (p less than 0.05). A possible role is suggested for copper-catalysed oxidative mechanisms in the pathogenesis of Parkinson's disease. PMID- 2886717 TI - Implantation of artificial sphincter for anal incontinence. AB - The implantation of an artificial anal sphincter in a man with severe anal incontinence an myasthenia gravis is described. The prosthesis used, an "AMS 800' artificial urinary sphincter, gave the patient complete control of defecation. The technique offers the possibility of curing anal incontinence of neuromuscular origin, for which there has been no treatment until know. PMID- 2886716 TI - Effect of hydrazine sulphate on whole-body protein breakdown measured by 14C lysine metabolism in lung cancer patients. AB - In a prospective double-blind trial twelve malnourished patients with lung cancer were randomised to receive either placebo or hydrazine sulphate (60 mg three times daily) for 30 days. Fasting lysine flux was determined by a primed 4-hour continuous infusion of 14C-lysine before and after one month of hydrazine treatment. Baseline plasma lysine flux was 2580 (SD 580) mumol/h for the placebo group and 2510 (440) mumol/h for the hydrazine group. After one month the placebo group showed a slight rise to 2920 (450) mumol/h (p = 0.08) and the hydrazine group showed a significant fall to 1840 (750) mumol/h (p less than 0.05); serum albumin fell in the placebo group and was unchanged in the hydrazine group. Administration of hydrazine sulphate to reduce aminoacid flux may favourably influence the metabolic abnormalities in cancer cachexia. PMID- 2886718 TI - Protection from autoimmune disease as the third function of the major histocompatibility gene complex. AB - The collection of genes known as the major histocompatibility gene complex (MHC) appears to subserve three functions. Firstly, its class I genes, coding for antigens on all nucleated cells, assist clones of cytotoxic T cells to kill virus infected cells quickly, without being muffled by the myriad numbers of free virus particles. Secondly, the absence of autoimmunity to both class I and class II MHC antigens shows that they impose unbreakable tolerances on the immune repertoire. The class II antigens, which are confined to B lymphocytes (if their apparent occurrence on other dividing cells is a cross-reaction), may have the sole function of tolerance induction, supplementing this activity of the class I antigens. Both sets of MHC antigens serve to diversify immunity-repertoire gaps among individuals of a population, thus hampering epidemic spread of infection and providing a diversity of immunoreactivity that favours survival of at least some members of a population in the face of pestilence. Thirdly, the permanence of the MHC tolerance inductions affords a powerful, adaptable mechanism for curtailment of reproductively disadvantageous autoimmune disease liable to arise through somatic mutations in lymphocytes multiplying under drive from a microbial antigenic stimulus. PMID- 2886719 TI - How far to lower blood pressure? PMID- 2886720 TI - HBV and glomerulonephritis. PMID- 2886721 TI - Nocturnal hypoglycaemia in childhood diabetes. PMID- 2886722 TI - Acromegalic heart disease. PMID- 2886723 TI - Management of Colles fractures. PMID- 2886724 TI - Audiological services for children. PMID- 2886725 TI - Endemic goitre in central China caused by excessive iodine intake. AB - Thyroid status was examined in children from two villages in central China where the iodine concentrations in drinking water were 462.5 and 54 micrograms/l. Goitres were present in 65% (n = 120) and 15.4% (n = 51), respectively. All children in both groups were clinically euthyroid and neurologically normal. Growth measurements and intellectual performance were similar in the two groups. Children from the high-iodine village had a lower mean serum triiodothyronine and higher serum free thyroxine and serum thyroid-stimulating hormone concentrations than the children from the control village. 2 cases of overt hypothyroidism were detected in the high-iodine village. PMID- 2886728 TI - Lyme disease in Europe. PMID- 2886726 TI - Portable ultrasound scanner versus serology in screening for hydatid cysts in a nomadic population. AB - 3553 nomads in Turkana, a remote area of north-west Kenya, were screened for hydatid cysts by a portable ultrasound scanner and by serology. 198 (5.6%) proved to have liver or upper abdominal cysts. In the group screened by both techniques (2644) 174 (6.6%) cases of hydatidosis were detected by ultrasonography and 76 (2.9%) by serology. Ultrasonography gave immediate results and was less expensive and more acceptable and educationally valuable to the people. This non-invasive rapid technique also provided important clinical information about the cysts. The prevalence data thus obtained will contribute to the surveillance of a hydatid control programme. PMID- 2886729 TI - Progress in the prevention and control of iodine-deficiency disorders. PMID- 2886727 TI - Postural body sway and exposure to high-energy impulse noise. AB - Detailed neurological and audiological examinations and body-sway measurements with a stable platform were carried out on 60 subjects who had been exposed to high-energy intermittent noise from firearms and had various degrees of noise induced hearing loss. The results were compared with those for 115 healthy controls. The exposed subjects showed significantly more body sway, estimated as movement of the centre of gravity in the horizontal plane, than the controls. This swaying correlated poorly with the recalled level of noise exposure, though subjects with more severe hearing loss (by audiometric deterioration of high frequency sound, 4 kHz and 6 kHz) showed more sway than those with less severe hearing loss. Age was not significantly correlated with body sway among the controls but men seemed to sway more than women. These results suggest subclinical disturbance of the vestibular system among subjects with impulse noise-induced hearing loss. PMID- 2886730 TI - Did the North Karelia project reduce coronary mortality? PMID- 2886731 TI - Does a siesta protect from coronary heart disease? PMID- 2886733 TI - Should transplant centres exchange kidneys? PMID- 2886732 TI - Testing of blood donations for non-A, non-B hepatitis. PMID- 2886734 TI - Cryptosporidiosis: a case of airborne transmission. PMID- 2886735 TI - Cerebrospinal fluid inflammation during OKT3 therapy. PMID- 2886737 TI - IVF and associated techniques: whom can we believe? PMID- 2886736 TI - Infantile spasms on weaning from breast milk containing anticonvulsants. PMID- 2886738 TI - Neonatal screening for hypercholesterolaemia. PMID- 2886739 TI - Cod liver oil or bust. PMID- 2886740 TI - Anaesthesia for tonsillectomy. PMID- 2886741 TI - Cattle as reservoir of verotoxin-producing Escherichia coli O157:H7. PMID- 2886742 TI - Early or low-grade melanoma? PMID- 2886743 TI - Food allergy in idiopathic nephrotic syndrome. PMID- 2886744 TI - Boycotts and medicine. PMID- 2886745 TI - Surgical training and overseas doctors. PMID- 2886746 TI - An ethical dilemma. PMID- 2886748 TI - Renal replacement for diabetics. PMID- 2886747 TI - The new genetics. PMID- 2886749 TI - Tropical spastic paraparesis. PMID- 2886750 TI - Proton spectroscopy of plasma and testing for malignancy. PMID- 2886751 TI - Does chloroquine cause hypoglycaemia in the absence of clinical malaria? PMID- 2886752 TI - Interaction of cyclosporin and itraconazole. PMID- 2886753 TI - Group-specific component and HIV infection. PMID- 2886754 TI - No evidence of HIV transmission after long-term follow-up of haemophiliacs treated with heat-treated factor VIII concentrate of American origin. PMID- 2886755 TI - Safety of albumin preparations manufactured from plasma not tested for HIV antibody. PMID- 2886756 TI - AIDS publicity campaigns. PMID- 2886757 TI - Private homes for elderly patients. PMID- 2886758 TI - Management of drug abuse. PMID- 2886759 TI - One-use needle-syringe for drug abusers. PMID- 2886760 TI - Lead and children's IQ. PMID- 2886761 TI - Distribution of interphase nucleolar organiser regions and diagnosis of malignancy. PMID- 2886762 TI - Cytomegalovirus pneumonitis after allogeneic marrow transplantation. PMID- 2886763 TI - High levels of cytomegalovirus antibody in patients requiring vascular surgery for atherosclerosis. AB - 157 caucasian male patients undergoing vascular surgery for atherosclerosis and a matched control group of patients with high cholesterol levels were screened for antibodies to cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV1) and type 2 (HSV2), indicative of persistent infection. The prevalence of CMV antibodies was higher in the surgical group than in the control group (90% and 74%, respectively), and a significantly greater percentage (p less than 0.001) of surgical cases than controls had high titres of CMV antibodies (57% and 26%, respectively). Small but not significant differences in antibodies to HSV1 were observed, and there were no differences in HSV2 antibody titres. For each virus there was no correlation between antibody titre and blood levels of total cholesterol or triglycerides. It is suggested that periodically activated virus may have a role in the pathogenesis of atherosclerosis. PMID- 2886764 TI - Histopathology in the prediction of relapse of patients with stage I testicular teratoma treated by orchidectomy alone. AB - 259 patients with stage I non-seminomatous germ-cell testicular teratoma who were treated by orchidectomy alone and monitored at one often centres in the United Kingdom were followed for a median of 30 months. 62 of the 70 relapses occurred in the first 18 months after orchidectomy. The 2-year relapse-free rate was 74%, falling to 68% at 4 years. Histological sections from 233 of the orchidectomy specimens were reviewed centrally. Four features independently predicted relapses: invasion of testicular veins, invasion of testicular lymphatics, absence of yolk-sac elements, and presence of undifferentiated tumour. An index, based on the number of these features observed, identified a high-risk subgroup of 55 patients who had a 42% relapse-free rate at 2 years. PMID- 2886765 TI - Serum cholesterol and cancer in the NHANES I epidemiologic followup study. National Health and Nutrition Examination Survey. AB - The relation between total serum cholesterol and cancer incidence and mortality was studied in a cohort based on a probability sample of the United States population. 5125 men (yielding 459 incident cancers and 258 cancer deaths) and 7363 women (398 cases, 186 deaths) were initially examined in 1971-75 and followed up for a median of 10 years. Men in the lowest cholesterol quintile had nearly double the risk of those in the highest quintile for both incidence and mortality. Among women a similar relation was seen for cancer mortality, but cancer incidence in the lowest quintile was only 1.2 times that of women in the highest quintile. The inverse cholesterol-cancer relation in men was present for cholesterol determinations made 6 or more years before diagnosis of cancer. It may be premature to dismiss the inverse relation between serum cholesterol and cancer simply as a preclinical marker of disease. PMID- 2886767 TI - Possible mechanism for cerebral oedema in diabetic ketoacidosis. AB - This hypothesis, presented to explain the cerebral oedema that sometimes occurs during treatment of diabetic ketoacidosis (DKA), is based on activation of the Na+/H+ exchanger, a ubiquitous plasma-membrane transport system that functions in the regulation of cytoplasmic pH. Experimental acidification of the cytoplasm with weak organic acids activates the exchanger and, in the presence of extracellular Na+, leads to cell swelling. This swelling is osmotic, secondary to a net gain in Na+ and the anion of the weak organic acid. In DKA, cytoplasmic acidification results from high levels of circulating weak organic acids (ketoacids and free fatty acids) and activation of Na+/H+ exchange would similarly be expected. Conditions during conventional treatment of DKA should favour even greater activation of the exchanger and additional cell swelling would be predicted. The hypothesis is consistent with the clinical observation that clinically apparent cerebral oedema occurs with improvement in the patient's acid-base status rather than at the peak of the ketoacidosis. PMID- 2886766 TI - Transferable enzymatic resistance to third-generation cephalosporins during nosocomial outbreak of multiresistant Klebsiella pneumoniae. AB - Klebsiella pneumoniae strains that were resistant to third-generation cephalosporins and amikacin were recovered from 62 of 395 patients (15.7%) during 1986. 25 isolates (40%) caused urinary tract infections. The outbreak involved three intensive care units (54 isolates), and spread from one unit to another and then to four wards (8 isolates). K pneumoniae of various serotypes and strains of different Enterobacteriaceae demonstrating the same antibiotic resistance pattern were isolated, which suggests dissemination of an R-factor. The isolates had low level resistance to third-generation cephalosporins (mode minimum inhibitory concentration of cefotaxime, 2 mg/l) but remained sensitive to cephamycins. Cefotaxime was effective in cases of uncomplicated urinary tract infection, but failed in major infections at other sites. 1-5 mg/l of the beta-lactamase inhibitors clavulanic acid or sulbactam restored normal activity to cefotaxime against the multiresistant strains. Resistance to third-generation cephalosporins was mediated by a new broad-spectrum enzyme of isoelectric point 6.3. Resistance to beta-lactams and aminoglycosides was transferable to Escherichia coli. The emergence of transferable enzymatic resistance to newer beta-lactams in K pneumoniae strains indicates a major risk of spread of such resistance to otherwise sensitive strains. PMID- 2886768 TI - Catheterisation of the fallopian tubes from the vagina. PMID- 2886769 TI - Consensus on heart failure management? PMID- 2886770 TI - Antibiotics by design. PMID- 2886771 TI - Diabetic skin, joints, and eyes--how are they related? PMID- 2886772 TI - Diurnal enuresis. PMID- 2886773 TI - A far-sighted approach to myopia and cataract. PMID- 2886774 TI - Repetition strain injury. PMID- 2886776 TI - Changing relation between home and clinic blood-pressure measurements: do home measurements predict clinic hypertension? AB - Blood-pressure screening in a family health centre identified 114 patients (53 male, 61 female) with diastolic pressures of 95 mm Hg and greater after three readings in the seated position (mean 163 [SEM 2]/104 mm Hg). All were instructed in the use of the 'Copal UA 231/251' electronic sphygmomanometer and produced a series of readings taken at home over 3 days. They were recalled after 2 weeks and 4 weeks for repeat clinic measurements of blood pressure. Blood pressure fell on successive clinic visits; at the final visit only 59 patients (31 male, 28 female) had diastolic pressures of 95 mm Hg or greater. Average day-time home blood-pressure measurements (155/94 mm Hg) were significantly lower than the screening blood-pressure measurements but were not significantly different from those at the third clinic visit (154/97 mm Hg). Home blood-pressure measurements were successful in predicting outcome at the third clinic visit in 90 (79%) patients; home-monitored pressures suggested normotension when the final clinic visit diastolic blood pressure was still above 95 mm Hg in only 16 (14%) patients. Only 2 of these had a final clinic diastolic pressure above 105 mm Hg. Home monitoring represents a practicable and acceptable alternative to repeated clinic measurements in the initial assessment of hypertensive patients. PMID- 2886775 TI - Evidence for protection by breast-feeding against infant deaths from infectious diseases in Brazil. AB - In a population-based case-control study of infant mortality in two urban areas of southern Brazil, the type of milk in an infant's diet was found to be an important risk factor for deaths from diarrhoeal and respiratory infections. Compared with infants who were breast-fed with no milk supplements, and after adjusting for confounding variables, those completely weaned had 14.2 and 3.6 times the risk of death from diarrhoea and respiratory infections, respectively. Part-weaning was associated with corresponding relative risks (RR) of 4.2 and 1.6. The risk of death from infections other than diarrhoea or respiratory infection was less clearly associated with breast-feeding (completely weaned, RR = 2.5; partly weaned, RR = 0.4). Cow's and formula milk seemed to be equally hazardous. For deaths due to diarrhoea the increased risk associated with not breast-feeding was greatest in the first two months of life (RR for completely weaned vs breast-fed without supplementary milk = 23.3). PMID- 2886777 TI - Beneficial effect of captopril in cardiogenic shock. PMID- 2886778 TI - HLA class II genes in chronic progressive and in relapsing/remitting multiple sclerosis. PMID- 2886779 TI - Tannin and oesophageal cancer. PMID- 2886780 TI - Abnormal red-blood-cell morphology in myalgic encephalomyelitis. PMID- 2886781 TI - Sotos syndrome and fragile X chromosomes. PMID- 2886782 TI - Epidemic pre-eclampsia. PMID- 2886783 TI - Hypertension in the puerperium. PMID- 2886784 TI - Bupivacaine concentration and obstetric delivery. PMID- 2886785 TI - Obstetrics in Subsaharan Africa. PMID- 2886786 TI - Treatment of non-neoplastic nipple discharge with fibrin adhesive. PMID- 2886787 TI - Huge cyclosporin overdose with favourable outcome. PMID- 2886788 TI - Borrelia burgdorferi antibodies and amyotrophic lateral sclerosis. PMID- 2886789 TI - Congenital hypertrophy of retinal pigment epithelium in non-Gardner's polyposis kindreds. PMID- 2886790 TI - Fibrin degradation products are not specific markers for thrombolysis in myocardial infarction. PMID- 2886791 TI - Propofol in anaesthesia. PMID- 2886792 TI - Yersinia enterocolitica infections and pork. PMID- 2886793 TI - Laboratory diagnosis of peritonitis in CAPD. PMID- 2886794 TI - Detection of HPV-16 by DNA dot blot hybridisation. PMID- 2886795 TI - Effect of heat on gentamicin assays. PMID- 2886796 TI - Pathophysiology of akathisia. PMID- 2886797 TI - Ventricular expression of atrial natriuretic peptide. PMID- 2886798 TI - Adrenoceptors in the diagnosis of phaeochromocytoma. PMID- 2886799 TI - Clinical test for congenital dislocation of hip. PMID- 2886800 TI - Mortality and social class. PMID- 2886802 TI - Abortion in the lobby. PMID- 2886803 TI - Overseas student electives and AIDS. PMID- 2886801 TI - Ethics of malnutrition research in children. PMID- 2886805 TI - Coronary heart disease mortality rates. PMID- 2886804 TI - Cervical cancer screening. PMID- 2886806 TI - Fatal renal failure due to indomethacin. PMID- 2886807 TI - Incidence of NSAID-related, severe gastrointestinal bleeding. PMID- 2886808 TI - Severe parkinsonism in two AIDS patients taking prochlorperazine. PMID- 2886809 TI - HIV and acute onset of psychosis. PMID- 2886810 TI - Does splenectomy enhance risk of AIDS in HIV-positive patients with chronic thrombocytopenia? PMID- 2886811 TI - Earlier detection of HIV and second-generation antibody assays. PMID- 2886812 TI - Autonomic neuropathy in AIDS. PMID- 2886813 TI - Effect of clonidine in child of normal stature. PMID- 2886814 TI - Trial of an attenuated bovine rotavirus vaccine (RIT 4237) PMID- 2886815 TI - Chronic cryptosporidial diarrhoea and hyperimmune cow colostrum. PMID- 2886816 TI - Handling balanopreputial adhesions. PMID- 2886817 TI - Life-threatening haemoptysis. PMID- 2886818 TI - Linkage analysis in manic-depressive illness. PMID- 2886819 TI - Small loss of chance of full recovery. PMID- 2886820 TI - Intravenous dihydroergotamine to relieve pelvic congestion with pain in young women. AB - The selective venoconstrictor dihydroergotamine (DHE) was given intravenously to 12 women with evidence of pelvic congestion. In 6 the effect of the drug on pelvic veins was observed by pelvic venography. After DHE there was a mean reduction of 35% in the diameter of the pelvic veins measured and the contrast medium cleared rapidly, with a visible reduction in pelvic congestion. In the other 6 women DHE was given during an acute attack of pelvic pain. The effect of the drug on pain relief was assessed by a single-blind crossover trial with intravenous saline as the placebo and by a visual analogue scale to assess the intensity of pain. Pain was significantly lower post-DHE 4 and 8 h and 2 and 4 days after treatment than after placebo. The results confirm a close association between demonstrable pelvic congestion and pelvic pain. PMID- 2886821 TI - Randomised comparison of cisplatin with cyclophosphamide/cisplatin and with cyclophosphamide/doxorubicin/cisplatin in advanced ovarian cancer. Gruppo Interegionale Cooperativo Oncologico Ginecologia. AB - 565 patients with stage III-IV epithelial ovarian cancer were randomly assigned to receive cisplatin (P), cyclophosphamide and cisplatin (CP), or cyclophosphamide, doxorubicin, and cisplatin (CAP). Data on 531 patients were analysed. Treatment with CAP resulted in a significantly higher overall (complete and partial) response rate (66 vs 56 vs 49% for CAP, CP, and P, respectively), but the rate of complete surgical response for the three treatment arms was similar (26, 21, and 20%). Size of residual tumour after first surgery and Karnofsky index were the best predictors of complete remission. Survival and disease-free survival were not significantly different in the three arms, although progression-free survival was significantly longer after CAP. However, tumour size, cell type, and Karnofsky index, but not therapy, were independent predictors for survival. Haematological toxicity was highest with CAP. The addition of cyclophosphamide or doxorubicin and cyclophosphamide to cisplatin does not substantially increase the number of potentially curable, advanced ovarian cancer patients. PMID- 2886823 TI - Magnetic resonance imaging of the spine in multiple myeloma. AB - The lower thoracic and lumbar spine of patients with multiple myeloma was examined by magnetic resonance imaging (MRI), plain radiography, and bone scintigraphy. Three independent investigators evaluated the power of these diagnostic methods to detect bone lesions in 192 vertebrae from 18 patients and in 60 vertebrae from 7 controls. 41 foci with abnormal signal intensity were detected by MRI; X-ray films showed osteolytic lesions in 4 vertebral bodies; and bone scanning was positive in 2 cases. The superiority of MRI in detecting myeloma-associated focal bone lesions was statistically significant, and in one case the lesions were confirmed at necropsy. Deviations in shape and height of vertebral bodies were slightly more easily visible on radiographs. Early detection of imminent medullary compressions in 2 patients led to successful radiotherapy before symptoms appeared. PMID- 2886822 TI - Influence of sympathetic nervous system on hypoglycaemic warning symptoms. AB - The effect of mild insulin-induced hypoglycaemia on symptoms, physiological changes, and adrenaline responses was assessed in 10 normal subjects and 15 insulin-dependent diabetic patients (5 with reduced awareness of hypoglycaemic symptoms). When blood glucose was maintained at 3.2 mmol/l, reaction time was prolonged in both normal and diabetic subjects and plasma adrenaline levels increased in the normals and some diabetics; there were no other physiological responses. 2 normals and 1 diabetic were aware that their blood glucose was low. When blood glucose was maintained at 2.5 mmol/l for 30 min, 9/10 normals but only 4/15 diabetics recognised hypoglycaemia. Increases in hypoglycaemic symptom score, tremor, and sweating, and falls in diastolic blood pressure were significant only in the normal subjects and the 4 "aware" patients. Adrenaline levels increased in all cases, but were more pronounced in the normals and aware diabetics. Reaction time remained prolonged in all groups. All measurements returned to baseline when blood glucose was raised to 4.5 mmol/l. Impairments in adrenaline response may be common, even in diabetic patients without autonomic neuropathy and in those who do not complain of hypoglycaemic unawareness; consequent failure to recognise a falling blood glucose may predispose to a risk of severe hypoglycaemia. PMID- 2886824 TI - Pathogenesis of post-herpetic neuralgia. AB - A model of post-herpetic neuralgia is put forward based on the physiological effects of herpes simplex type-1 virus infection of rat dorsal root ganglion neurons in tissue culture. This virus causes these normally electrically silent neurons to produce spontaneous action potentials. Furthermore, pairs of neurons tend to have synchronised discharges. This coupling is not synaptically mediated, but due to presumed electrical junctions. It is proposed that post-herpetic neuralgia is caused by abnormal impulses arising in dorsal root ganglion neurons as a direct result of viral infection. PMID- 2886826 TI - Restrictive cardiomyopathy or constrictive pericarditis? PMID- 2886825 TI - Awareness of hypoglycaemia in diabetes. PMID- 2886827 TI - Looking inside arteries. PMID- 2886828 TI - Bone erosions in rheumatic disease. PMID- 2886829 TI - Treatment of menorrhagia. PMID- 2886830 TI - An odd way to license a drug. PMID- 2886831 TI - Disease, lifestyle, and consanguinity in 58 American Gypsies. AB - Medical data on 58 Gypsies in the area of Boston, Massachusetts, were analysed together with a pedigree linking 39 of them in a large extended kindred. Hypertension was found in 73%, diabetes in 46%, hypertriglyceridaemia in 80%, hypercholesterolaemia in 67%, occlusive vascular disease in 39%, and chronic renal insufficiency in 20%. 86% smoked cigarettes and 84% were obese. Thirteen of twenty-one marriages were consanguineous, yielding an inbreeding coefficient of 0.017. The analysis suggests that both heredity and environment influence the striking pattern of vascular disease in American Gypsies. PMID- 2886832 TI - Non-steroidal anti-inflammatory drugs and hospital admission for perforated peptic ulcer. AB - The frequency of hospital admission for perforated ulcer was not measurably affected by concurrent use of non-steroidal anti-inflammatory drugs (NSAID) during nearly 30 million person-days of NSAID use at Group Health Cooperative of Puget Sound. Whether patients had ever used cimetidine or antacids, drugs which indicate the presence of ulcer disease or symptoms, was strongly predictive of perforation in the same population (rate ratio 5.1; 95% CI 2.6-10.0). Perforation rates increased sharply with age but were similar for men and women. PMID- 2886834 TI - Debrisoquine metabolism in parkinsonian patients treated with antihistamine drugs. PMID- 2886835 TI - Effect of weather on daily pain score in rheumatoid arthritis. PMID- 2886833 TI - Hypoglycaemia unawareness in diabetics transferred from beef/porcine insulin to human insulin. AB - The case-histories of 3 patients with insulin-dependent diabetes mellitus (IDDM) suggested that, after a switch from beef/porcine to human insulin, a given level of hypoglycaemia may cause less pronounced sympathoadrenal symptoms (tremor, sweating, &c), so that there is less warning of impending unconsciousness. This possibility was investigated by questioning of 176 IDDM patients who had switched from beef/porcine to human insulin with negligible change in dosage 1-48 months earlier. 66 (36%) said that their symptoms of hypoglycaemia had changed from those of sympathoadrenal activation to those of neuroglycopenia. This disadvantage of human insulin is an argument for continued availability of beef/porcine insulin. PMID- 2886836 TI - Mupirocin-resistant Staphylococcus aureus. PMID- 2886838 TI - Albinism in South African blacks. PMID- 2886837 TI - Need for acceptable measures of disease progression in rheumatoid arthritis. PMID- 2886839 TI - Absence of secretory response in jejunal biopsy samples from children with cystic fibrosis. PMID- 2886840 TI - Isolation of human lymphotropic herpesviruses from Uganda. PMID- 2886841 TI - A novel lymphotropic herpesvirus. PMID- 2886842 TI - Hallucination during sustained-release morphine and methadone administration. PMID- 2886843 TI - Fetal cerebral vascular resistance. PMID- 2886844 TI - Frequency of epilepsy preceding stroke. PMID- 2886845 TI - Vascular malformations and hypogammaglobulinaemia. PMID- 2886847 TI - Smoking and health in China. PMID- 2886846 TI - Is Clostridium difficile endemic in chronic-care facilities? PMID- 2886848 TI - Antibiotics for exacerbations of chronic bronchitis. PMID- 2886850 TI - Short-term intensive therapy for childhood non-Hodgkin lymphoma. PMID- 2886849 TI - Prognosis of meningococcal septicaemia. PMID- 2886851 TI - Information for drug trial participants. PMID- 2886852 TI - Dual meaning of membership. PMID- 2886853 TI - Sugar. PMID- 2886855 TI - Future of IPPNW. International Physicians for the Prevention of Nuclear War. PMID- 2886854 TI - Campylobacter pylori and peptic ulcer. PMID- 2886856 TI - Ursodeoxycholic acid for primary biliary cirrhosis. PMID- 2886857 TI - Inhibition of activation of lymphokine-activated killer cells in vitro by the heparin preservative benzyl alcohol. PMID- 2886858 TI - Postnatal transmission of HIV from mother to child. PMID- 2886859 TI - Breast-feeding and HIV infection. PMID- 2886860 TI - Female-to-female transmission of HIV. PMID- 2886862 TI - HIV-2 in Brazil. PMID- 2886861 TI - Allografts as vectors of infection. PMID- 2886863 TI - Familial retinol-binding-protein deficiency. PMID- 2886864 TI - Interference by acetazolamide in theophylline assay depends on the method. PMID- 2886865 TI - Abnormal peripheral lymphocytes in tropical spastic paraparesis. PMID- 2886866 TI - Can HTLV-1 lead to immunological disease? PMID- 2886867 TI - Atrial natriuretic peptide during pregnancy. PMID- 2886868 TI - Rapid diagnosis of cytomegalovirus infection by detection of early antigen fluorescent foci. PMID- 2886869 TI - Bereavement and severe dementia. PMID- 2886870 TI - Involuntary hospital admission under Section 47 of the National Assistance Act. PMID- 2886871 TI - Effects of tumor promoters (mezerein, teleocidin and palytoxin) on growth hormone secretion from rat anterior pituitary cells cultured in monolayer. AB - The effects of compounds with tumor promoting activity (mezerein, teleocidin and palytoxin) on rat growth hormone (rGH) release was compared to that of TPA (12-O tetradecanoyl phorbol-13-acetate). Mezerein and teleocidin both of which are activators of protein kinase C (TPA type tumor promoter), elicited rGH release about 3.5 to 4 fold above control values. The ED 50 was 16 nM for mezerein, 1.1 nM for teleocidin and 1.5 nM for TPA. In contrast to mezerein or teleocidin, a non-TPA type tumor promoter (palytoxin) which does not activate protein kinase C failed to stimulate rGH release. These observations suggest that the activation of protein kinase C is essential in the release of rGH induced by the tumor promoters. PMID- 2886872 TI - Dietary sodium intake and age in spontaneously hypertensive rats: effects on blood pressure and sympathetic activity. AB - Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were placed on sodium restricted diets (9 and 17 mumol/g) or on a regular sodium diet (101 mumol/g) at 2, 4, 7, or 10 weeks of age, and continued until 16 weeks of age. Severe sodium restriction (9 mumol/g) initiated at 2 or 4 weeks of age prevented hypertension development in SHR and severely retarded growth. Hypertension development was attenuated when 9 mumol/g was initiated at 7 weeks of age, and was not affected when started at 10 weeks of age. Mean arterial pressure (MAP) in WKY receiving 9 mumol Na/g initiated at 2 and 4 weeks of age was below normal, but was not affected when this diet was given at 7 or 10 weeks of age. Less severe sodium restriction (17 mumol Na/g) resulted in a reduction in hypertension development when initiated at 2, 4, and 7 weeks of age, but not at 10 weeks of age. MAP was normal in WKY receiving 17 mumol Na/g at all ages of diet initiation. When the 9 or 17 mumol Na/g diet were initiated at 2, 4, and 7 weeks of age, the response of blood pressure to hexamethonium administration was blunted in SHR relative to both WKY receiving the same diet, and to control SHR receiving 101 mumol Na/g. We conclude that both WKY and SHR require a minimum amount of dietary sodium for normal growth and for the achievement of normal BP in WKY, and hypertension in SHR. This sodium requirement decreases with age. SHR and WKY exhibit similar sensitivities to sodium intake with respect to body weight, but the effects on BP are more pronounced in SHR. The BP lowering effects of dietary sodium restriction may be due to a blunting of the pressor effectiveness of the sympathetic nervous system. PMID- 2886874 TI - Symposium on Analysis of Neurotransmitters. April 7-10, 1987, Stockholm, Sweden. Proceedings. PMID- 2886873 TI - GABA interaction with lipids in organic medium. AB - The interaction of 3H-GABA (gamma-aminobutyric acid and 14C-glutamate with lipids in an aqueous organic partition system was studied. With this partition system 3H GABA and 14C-glutamate were able to interact with sphingomyelin, sulfatide, phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and phosphatidic acid but not with cholesterol or ceramide. In an homogeneous aqueous medium we could not demonstrate any interaction between 3H-GABA and lipids. The apparent dissociation constants (Kd) for 3H-GABA-lipids or 14C-glutamate-lipids interactions in organic medium were in the millimolar range and maximal charge (Bmax) between 3 and 7 moles of GABA or glutamate by mole of lipid. Amino acids such as glutamic acid, beta-alanine and glycine displaced 3H-GABA with the same potency as GABA itself; thus these results show that the interaction lacks pharmacological specificity. To detect this interaction lipid concentrations higher than 2 microM were required and in the partition system 3H-GABA and lipid phosphorus were both concentrated at the interface. Therefore lipids tested with a biphasic partition system do not fulfill the classical criteria for a neurotransmitter receptor at least not for GABA and glutamate. PMID- 2886875 TI - Effects of psychotropic drugs on neurotransmitters in man. AB - Primary biochemical profiles of antidepressants and neuroleptics are summarized in comparison to their actual effects on monoamine neurotransmitters in humans during the time period when clinical response emerges. Even the most biochemically specific of these drugs produces effects on at least two monoamines by three to four weeks. Interestingly, taking into account relative changes in dopamine and serotonin metabolites in cerebrospinal fluid relates better to the primary biochemical action(s) of each drug than do absolute changes. Moreover, monoamine changes after drugs are in the opposite direction to those after ECT, suggesting that balance among rather than shifts in single neurotransmitters is the relevant target of major psychotropic drugs. PMID- 2886876 TI - Analysis of amino acids: neurochemical application. AB - For high sensitivity analysis of neuroactive amino acids, liquid chromatography employing precolumn derivatisation with o-phthalaldehyde (OPA) is suitable for several reasons. The OPA reagent is non-fluorescent per se, the reaction occurs rapidly in alkaline aqueous solutions and forms highly fluorescent derivatives with primary amines. PMID- 2886877 TI - Bioanalytical aspects on method validation. AB - The validation of methods for neurotransmitter amines and metabolites depends on various sample related factors such as interferences, complexity of matrix composition, analyte stability or variations in concentration due to changing physiological responses. Also, the ultimate precision and accuracy of a method in whole would be related to the complexity of the sample work up procedure, the efficiency and reproducibility of the separation system, the use of a suitable internal standard to correct for volumetric errors and the sensitivity, linearity and selectivity of the detection system. A critical factor in the validation of those methods based in the chromatographic separation of the analyte is the confirmation of peak homogeneity through procedures such as changes on retention time, collection of analyte and reinjection into another system, correlation of recoveries in both systems, pharmacological manipulations prior to the assay or collection and derivatization followed by rechromatography. Isotope dilution GC MS is widely accepted as a definitive reference method for its accuracy and precision although, as it is not always available, crossvalidation between different non-mass spectrometric methods is often given as proof of analytical reliability. PMID- 2886878 TI - Concepts in the validation of neurochemical methods: the proper generation and use of statistics. AB - Nearly every advance made in the study of neurotransmission has resulted from the development of new analytical methods or from the application of such methods to neurochemical problems in new ways. Each investigator places extremely high dependence on the laboratory method from which the data are gathered. It is therefore vital that these methods be proven valid when first selected and when used throughout the experiments being conducted. The process of method validation has flourished and been refined in the field of laboratory medicine. Methods are primarily validated by their accuracy and reproducibility in determining the analyte of interest in the tissue(s) to be studied. It is important that standards of performance be established that will allow objective decisions to be made when methods are tested for these characteristics. Performance standards for several neurotransmitters are suggested. Studies performed to collect method performance data are presented. From these data, statistics can be generated that help to estimate analytical errors. Guidelines for the proper generation and use of these statistics are discussed. Use of these validation approaches should be expanded in the whole of neurochemistry, which should enrich the data gathered within a laboratory and improve the harmonization between laboratories. PMID- 2886879 TI - In vivo microdialysis--a new approach to the analysis of neurotransmitters in the brain. AB - Microdialysis is a new technique to monitor levels of chemical compounds in the extracellular space over time. It involves the implantation of a microdialysis probe into the brain tissue. The probe is similar to a push-pull probe but the perfusate is contained inside a semi-permeable membrane located at the tip of the probe. Substances in the extracellular fluid will diffuse into the perfusate while substances included in the perfusate will diffuse into the tissue. This principle opens up a wealth of possibilities to monitor chemical events within the brain and to study the working mechanism of various drugs. The perfusate may be analysed by a number of different techniques. In this paper we give a short summary of various HPLC techniques that have proven particularly useful. PMID- 2886880 TI - Radioenzymatic analysis of neurotransmitters. AB - Since the late 1960's, radioenzymatic assays have gradually come to replace the less sensitive and less specific spectrofluorometric and bioassay procedures previously used to determine many of the neurotransmitters. These assays provide the means to measure picogram quantities of most of these substances, and have enabled determinations to be made in very small volumes of body fluids, in brain perfusates and individual brain nuclei, and in large individual cells of some simple animals. This paper reviews briefly some of the radioenzymatic techniques presently available for assaying norepinephrine (NE), epinephrine (E), dopamine (DA), serotonin, and the trace amines octopamine (OA), phenylethanolamine (PEOHA), phenylethylamine (PEA), tyramine (TA) and tryptamine (T). PMID- 2886881 TI - The radioreceptor assay: a simple, sensitive and rapid analytical procedure. AB - Radioreceptor assays (RRAs) are analogous in concept to radioimmuno assays. Characteristic to both methods is the saturable, specific, competitive and reversible ligand/receptor interaction. The RRA is simple, sensitive and reproducible and provides a degree of precision comparable to more sophisticated analytical techniques. Since RRAs require little specialized equipment, they can be used routinely by any laboratory engaged in biochemical research or, as an inexpensive exercise to teach the fundamentals of ligand binding and analytical pharmacology. PMID- 2886882 TI - Application of combined gas chromatography/mass spectrometry to neurotransmitter research. AB - The features of flexibility, sensitivity and specificity continue to make GC/MS a valuable technique for identification and quantification of neuro-transmitters and related compounds. In this report four recent examples are presented which highlight the potentials of this technique. The traditional concept that GC/MS equipment is expensive and complex to operate warrants reconsideration in light of recent manufacturing trends in automation, computerization and the introduction of cheaper bench-top models. PMID- 2886883 TI - EC array sensor concepts and data. AB - The use of multiple parameter assays of entire metabolic pathways is potentially a powerful tool for unraveling mechanisms of disorders or drug action and classification of neurological diseases. Coulometric electrode series array sensors, coupled with liquid chromatography (n-ELC), provide a route to multiplying the resolving power of conventional LC by factors of 10 to 50. Since the original description of the n-ELC concept by Matson et al. (1), fundamental issues of optimizing sensor design and integration with computer controlled LC systems have been addressed. Femtogram level potential time (ET) separations can now be performed for multiple components in both isocratic and gradient modes. A 56-component isocratic method for the study of the kynurenine system in Huntington's Disease (HD) is presented as an indication of the analytical definitions and nomenclature used to qualify an n-ELC procedure, and an indication of the implications of multiparameter data bases on data handling and experimental design. PMID- 2886884 TI - Bio-medical applications of high performance liquid chromatography (HPLC) with amperometric detection. AB - Electrochemical detection of eluted solutes in HPLC is now well established as a selective and highly sensitive technique. Measurement of catecholamines and metabolites has been the most popular application with an exponential increase in literature. Recent improvements include the use of diphenylborate for extractions, the introduction of smaller diameter HPLC materials which improve resolution and sensitivity, and the replacement of carbon paste with glassy carbon which now gives a more stable electrode with similar sensitivity. Applications of HPLC with amperometric detection to the determination of drugs, amino acids and peptides are discussed. PMID- 2886885 TI - Analytical techniques for the determination of phenolic amine neurotransmitter conjugates. AB - This paper reviews methods developed in the author's laboratory for the measurement of the two sulfate conjugates of dopamine in biological material. The methods are sensitive enough for most applications relating to dopamine sulfate. Some are applicable to measurement of sulfate conjugates of other phenolic amines. PMID- 2886886 TI - Effects of highly potent octapeptide analogs of somatostatin on growth hormone, insulin and glucagon release. AB - Biological activities of highly potent octapeptide analogs of somatostatin (SS), D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) and D-Phe-Cys-Tyr-D-Trp-Lys-Val Cys-Thr-NH2 (RC-121), were investigated in male rats. When analog RC-160 was administered to rats in which serum growth hormone (GH) levels were elevated by pentobarbital anesthesia, a dose-related inhibition of GH was obtained at dose range of 0.1 to 2.5 micrograms/kg. The time course of GH inhibition by RC-160, RC 121 and SS-14 was studied in rats treated with phenobarbital, morphine and chlorpromazine. Analogs RC-160 and RC-121 induced a prolonged inhibition of GH levels, in contrast to SS-14, whose effect was short-lived. The analogs suppressed the GH level for more than 2 hr, the peak inhibition being seen 30 to 60 min after the injection. The effects of analogs RC-160 and RC-121 on insulin secretion were observed in rats, in which insulin levels had been elevated by intravenous administration of glucose (500 mg/rat). Administration of RC-160 suppressed insulin secretion, dose-dependently, maximum but not complete inhibition being achieved at a dose of 100 micrograms/kg. In this model, RC-160 and RC-121, in doses of 30 micrograms/kg, induced a similar inhibition of insulin release as 200 micrograms/kg of SS-14, whose action of SS-14 was transient. The effect of analog RC-160 on glucagon release was studied in rats with glucagon levels elevated by hypoglycemia. RC-160 suppressed the secretion of glucagon, the inhibition being dose-dependent in the range of 0.1 to 2 micrograms/kg. Doses of 2 and 10 micrograms/kg of this analog completely suppressed the hypoglycemia induced glucagon release. These results indicate that analogs RC-160 and RC-121 possess prolonged and enhanced biological activities, the former analog showing a high selectivity in inhibiting GH and glucagon release in vivo as compared with that of insulin secretion. PMID- 2886887 TI - The effects of somatostatin and some of its tetrapeptide fragments on ethanol induced gastric mucosal erosion in rat. AB - A study was made of the cytoprotective effects of somatostatin (SRIF) and its 3 6, 5-8, 7-10, 9-12 and 11-14 tetrapeptide fragments on absolute ethanol-induced haemorrhagic erosions in the stomach of rat. The SRIF molecule was found to prevent the gastric erosions induced by ethanol. The 7-10 and 11-14 fragments exhibited similar properties. There are two peaks in the cytoprotective dose response curves. It is concluded that various fragments of SRIF can also exert cytoprotective effects. PMID- 2886888 TI - Comparison of the butyrate effects on neurotransmitter receptors in neurohybrids NG108-15 and NCB-20 cells. AB - Our previous study demonstrated that long term treatment of NCB-20 cells with sodium butyrate resulted in a marked increase in the density of delta-opioid receptors with a much lesser effect on muscarinic cholinergic and no effect on alpha 2-adrenergic receptors. In the present study we investigated the effect of sodium butyrate on these three types of receptors in NG108-15 cells whose neuroblastoma parent is the same as that of NCB-20 cells. Long term treatment of NG108-15 cells with sodium butyrate (0.5 mM) induced a 2-fold increase in the density of the specific binding of 3H-clonidine. A comparable increase in the number of binding sites was detected when 3H-yohimbine was used as the receptor ligand. The butyrate-induced increase in the alpha 2-adrenergic receptor binding could be totally abolished by treatment with a protein synthesis inhibitor, cycloheximide, suggesting that synthesis of receptor protein is involved. The same butyrate treatment had no significant effect on opioid and muscarinic cholinergic receptor bindings. Thus, butyrate effects on the expression of these three types of receptors in NG108-15 and NCB-20 cells are dramatically different. These data suggest that induction by butyrate of neurotransmitter receptors requires concerted action of genetic factors of both parents of the neurohybrids. PMID- 2886889 TI - Combined cardiovascular effects of vecuronium and high-dose fentanyl in patients with poor left ventricular function undergoing coronary bypass grafting. PMID- 2886890 TI - [Clinical applications of the Southern blotting of DNA in hematology and oncology]. PMID- 2886891 TI - DNA polymorphisms for the nerve growth factor receptor gene exclude its role in familial dysautonomia. AB - Alleles for the single human nerve growth factor receptor gene (NGFR) on chromosome 17q can be distinguished by two polymorphic restriction sites for XmnI and one for HincII. The combined information content for haplotypes is quite high, making the NGFR locus an excellent genetic marker. Two of these polymorphisms were used to follow the inheritance of NGFR alleles in families with two or more members affected with familial dysautonomia. This rare disease is inherited in an autosomal recessive mode in the Ashkenazic Jewish population. Affected individuals show a severe depletion of NGF-dependent nerve populations from birth. Linkage analysis excluded a role for NGFR in this disease with odds of greater than 10(6):1 against the dysautonomia gene being within 1 centiMorgan of the mutation. In a previous study the gene for the beta subunit of NGF (NGFB) was also excluded in this disease. A possible role for other genes involved in NGF action or those coding for other developmentally determining neuronal factors is indicated. PMID- 2886892 TI - Fimbrial phase variation and DNA rearrangements in uropathogenic isolates of Escherichia coli. AB - Having previously shown that the oscillating on-off expression (phase variation) of type 1 fimbriae in Escherichia coli is regulated genetically by an invertible element of DNA, we wished to determine whether E. coli isolates recovered from infected humans behaved in similar fashion. We examined four different clinical isolates that expressed type 1 fimbriae, P fimbriae, or both. Using, in Southern blot analysis, a DNA probe from the type 1 fimbrial switch, that hybridized to one DNA band from phase-on bacteria and to two DNA bands from phase-off bacteria, we found that the three clinical isolates expressing type 1 fimbriae contained the same invertible switch previously seen in the K-12 isolate. Employing a similar approach to characterize the on-off expression of P fimbriae, we used a DNA probe containing the known transcriptional signals for P fimbriae. Although we detected DNA rearrangement in the two strains expressing P fimbriae, unlike the case for type 1 fimbriae, the rearrangement did not correlate with the on-off state of the P fimbriae. Rather, the DNA rearrangement correlated with the environmental conditions of growth of the bacteria from which the DNA was isolated. These results confirm the notion that P fimbriae expression and type 1 fimbriae expression are controlled differently. PMID- 2886894 TI - Board of Medicine looks at the benzodiazepine issue. PMID- 2886893 TI - An interchromosomal gene conversion of the Drosophila dunce locus identified with restriction site polymorphisms: a potential involvement of transposable elements in gene conversion. AB - Females heterozygous for the two alleles dnc2 and dncM14 of the X-linked gene dunce (dnc), and carrying a copy of dnc+ on the second chromosome, have produced a cluster of six dnc+ progeny X-chromosomes from recombination experiments. Restriction site polymorphisms have been used as genetic markers to follow the parentage of dnc locus segments in these chromosomes. All six chromosomes are identical with respect to the spectrum of restriction site markers they carry in the dnc+ chromosomal region. In the progeny chromosomes, this region is comprised of sequences like the dncM14 X-chromosome and the translocation copy of dnc+. Sequences flanking the dnc gene in the progeny chromosomes are like the dncM14 chromosome. Internal to the gene but near the 5' end, is a segment from the dnc+ translocation which has apparently originated from an interchromosomal and premeiotic gene conversion event. In addition, two transposable elements have inserted into the progeny chromosomes, one towards the 5' end of dnc and the other near the 3' end. The insertion of these elements occurred premeiotically since all six chromosomes are structurally identical. The data are interpreted with respect to a potential role of transposable element transposition in the process of gene conversion. PMID- 2886895 TI - Ketoconazole, leukotrienes, Paf-acether and nicotine as a hapten: the possible aetiology of seborrhoeic dermatitis. AB - There is evidence in some individuals that seborrhoeic dermatitis is an immuno allergic reaction induced by nicotine as hapten. Nicotine is present in passive smoking, botanic areas, some foods at very low levels, smokeless tobacco and chewing gums. The successful use of topical ketoconazole as an anti-fungal treatment has been recently explained by its anti-leukotrienes properties in vitro, in vivo and by its capacity to inhibit the leukotrienes-mediated anaphylactic bronchoconstriction in the guinea-pigs. The occurrence of hypersensitivity to nicotine in seborrhoeic dermatitis remains to be determined, but an other original view is open for a better comprehension of an old disease. PMID- 2886897 TI - Fetal and neonatal effects of drugs administered in labour. PMID- 2886896 TI - Relative effectiveness and costs of antiulcer medications as a basis for rational prescribing. AB - To be maximally effective, antiulcer medications should relieve ulcer symptoms rapidly and promote rapid healing of an ulcer crater; after the cessation of a course of treatment the ulcer should not recur. A wide variety of agents is available. These are of similar efficiency in the control of ulcer symptoms and in the acceleration of the healing of the ulcer crater. However, evidence exists of differences in the rate of the recurrence of duodenal ulcers on the cessation of these drugs. Surface-active agents (bismuth complexes, sucralfate, prostaglandins and carbenoxolone) are consistently superior to H2-histamine receptor antagonist drugs (cimetidine and ranitidine). A high relapse rate produces more patients with active disease at any one time, hence more patients will be exposed to the complications of the disease, and will require active investigation and therapy. Because of the increased rate of relapse, the use of H2-receptor antagonist drugs as first-line intermittent healing therapy can be shown to be associated with an eight-fold (800%) increase in cost of pharmaceutical agents as compared with first-line treatment with bismuth salts; a four-fold increase compared with the cost of using antacid drugs; and a two-fold increase compared with the cost of using sucralfate. When maintenance therapy with H2-receptor antagonist agents is given instead of intermittent therapy with bismuth complexes, a 14-fold increase in pharmaceutical costs is incurred, with inferior results that have already been demonstrated under the conditions of a controlled clinical trial. These considerations of efficacy and cost suggest that H2-receptor antagonist drugs ought not to be first-line therapy for duodenal ulcers; rather, surface-active agents such as colloidal bismuth or sucralfate should be prescribed initially. PMID- 2886898 TI - [Clinical pharmacology of benzodiazepines]. PMID- 2886899 TI - Anesthetic considerations in Beckwith-Wiedemann syndrome. AB - The anesthetic management of a thirty-month-old male with Beckwith-Wiedemann Syndrome is described. The presentation and features of this syndrome are described and the problems of providing anesthesia in such patients are discussed. PMID- 2886900 TI - Effect of fazadinium on respiratory functions and its correlation with neuromuscular transmission in children. AB - Effects of fazadinium in doses of 0.75, 1.0 and 1.25 mg/kg and pancuronium 0.1 mg/kg on respiratory functions (tidal volume, minute volume and inspiratory force) and correlation between respiratory functions and neuromuscular transmission were evaluated in 64 children aged 6 months to 12 years undergoing various types of elective surgery. Neuromuscular transmission was evaluated by a digitial EMG system using train-of-four stimuli calculating T1 and T4 ratios. Time to apnea, duration of apnea, time and mode of recovery of respiratory functions and neuromuscular transmission when spontaneous respiration started and recovered completely were recorded. The speed, depth and duration of effect of fazadinium on respiration were dose related, 0.75 mg/kg being inadequate to produce apnea in the majority of cases. Duration of apnea increased significantly with increasing dosage (13 +/- 2, 17 +/- 2, 23 +/- 2 minutes respectively). At the end of surgery respiratory measurements reached control values either spontaneously or after reversal. Spontaneous recovery took significantly longer times (34 +/- 3, 51 +/- 5, 95 +/- 10 minutes respectively) depending on dosage. In the remaining patients recovery was complete within five minutes after reversal. Pancuronium could be placed between 1.0 and 1.25 mg/kg fazadinium regarding aspects other than speed of onset of effect. Neuromuscular transmission was still markedly depressed when spontaneous respiration started (T4/T1 of 7 24%) and recovered (T4/T1 of 35-57%) indicating that when recovery from neuromuscular blockade is to be evaluated clinically, adequancy of ventilation by itself should not be taken as a sign of recovery from the effect of relaxant. PMID- 2886901 TI - Icotidine, an antagonist of histamine at both H1 and H2 receptors. AB - SK&F 93319 (icotidine), 2-[4-(3-methoxypyrid-2-yl)butylamino]-5-[(6-methylpyrid-3 yl )-methyl]- pyrimidin-4-one trihydrochloride, has been identified as a novel agent which combines into one molecule the ability to antagonize the actions of histamine at H1 and H2 receptors across a similar concentration or dose range. The degree of antagonism of vascular responses to histamine exceeds that possible with either an H1- or H2-receptor histamine antagonist alone. SK&F 93319 may have therapeutic utility in conditions requiring simultaneous antagonism of histamine at H1 and H2 receptors. PMID- 2886902 TI - H-1 blockers--classical antihistamines. AB - The H1-blocking antihistamines pharmacology, pharmacokinetics, uses, toxicity and special precautions are presented. Newer agents may offer advantages of longer half-life and lower levels of sedation and motor impairment. Therapeutic considerations are listed with attention to sustained therapeutic efficacy. PMID- 2886903 TI - H2-receptor antagonists: development and application. AB - The advent of H2-receptor antagonists has dramatically advanced the understanding and treatment of peptic ulcer disease. Ranitidine and cimetidine have been shown to be safe and effective in healing duodenal and gastric ulcers and in prevention of duodenal ulcer relapse. Due to differences in chemical structure, ranitidine is more potent and has a longer duration of action and fewer side effects than cimetidine. The current trend in therapy is toward less frequent dosing patterns with more attention toward controlling nocturnal acid secretion. Possibilities for other therapeutic uses of H2-receptor antagonists are suggested. PMID- 2886905 TI - Treatment of upper and lower airway disease with azelastine. AB - Azelastine is capable of interfering with a wide variety of mediators of airway hyperreactivity and provides significant protection and bronchodilation in allergic hay fever and allergic asthma, respectively. Clinical studies have shown that azelastine produces clinically significant bronchodilation of long duration in moderate to severe reversible lower airway disease. In addition, azelastine has been shown to have an effect on the upper airways by effective symptom relief in patients with seasonal allergic rhinitis; furthermore, azelastine affords protection against exercise and allergen provocation. PMID- 2886904 TI - Histamine receptors in the lung. AB - The availability of specific histamine receptor antagonists has provided evidence that human airways have both H1 and H2 receptors. H1 receptors, which mediate bronchoconstriction, predominate. H1 receptor antagonism can produce significant bronchodilatation in some asthmatics, block bronchoconstriction induced by antigen and histamine inhalation challenge, and have some protective effect against exercise and aspirin-induced bronchoconstriction. H2 receptors mediate bronchodilatation, but this effect is relatively weak in man. The role of classic antihistamines (H1 receptor antagonists) in the treatment of asthma has not been established. Since factors that precipitate asthma are quite varied, these agents may provide benefit in select patients. The availability of new, nonsedating H1 receptor antagonists show some promise in this regard. Future studies may more precisely define their use in asthma therapy. PMID- 2886906 TI - Effect of ethanol on mouse cerebral cortical beta-adrenergic receptors. AB - Low concentrations of ethanol (10-100 mM), added to assays in vitro, altered agonist (isoproterenol) binding to mouse cerebral cortical beta-adrenergic receptors in a reversible manner. Ethanol decreased the affinity of the high affinity form of the receptor for isoproterenol but had no effect on the affinity of the low affinity form of the receptor, the proportion of high and low affinity forms of the receptor, the total number of agonist-binding sites, or antagonist binding. The selective effect of ethanol on the properties of the high affinity agonist-binding site suggested that ethanol alters the characteristics of the complex of the receptor and Gs, the guanine nucleotide-binding protein. In cerebral cortical membranes of mice that had ingested ethanol chronically, isoproterenol binding data were best fit by a one-site model, even in the absence of guanine nucleotides. This change, when considered together with previously reported changes in adenylate cyclase activity, is reminiscent of heterologous desensitization of the beta-adrenergic receptor. Thus, both acute and chronic ethanol administration may produce changes in adrenergic function in brain. PMID- 2886907 TI - Isolation of human cDNAs for asparagine synthetase and expression in Jensen rat sarcoma cells. AB - Asparagine synthetase cDNAs containing the complete coding region were isolated from a human fibroblast cDNA library. DNA sequence analysis of the clones showed that the message contained one open reading frame encoding a protein of 64,400 Mr, 184 nucleotides of 5' untranslated region, and 120 nucleotides of 3' noncoding sequence. Plasmids containing the asparagine synthetase cDNAs were used in DNA-mediated transfer of genes into asparagine-requiring Jensen rat sarcoma cells. The cDNAs containing the entire protein-coding sequence expressed asparagine synthetase activity and were capable of conferring asparagine prototrophy on the Jensen rat sarcoma cells. However, cDNAs which lacked sequence for as few as 20 amino acids at the amino terminal could not rescue the cells from auxotrophy. The transferant cell lines contained multiple copies of the human asparagine synthetase cDNAs and produced human asparagine synthetase mRNA and asparagine synthetase protein. Several transferants with numerous copies of the cDNAs exhibited only basal levels of enzyme activity. Treatment of these transferant cell lines with 5-azacytidine greatly increased the expression of asparagine synthetase mRNA, protein, and activity. PMID- 2886908 TI - Molecular cloning and characterization of the cys-3 regulatory gene of Neurospora crassa. AB - The regulatory gene cys-3+ controls the synthesis of a number of enzymes involved in sulfur metabolism. cys-3 mutants show a multiple loss of enzymes in different pathways of sulfur metabolism. The cys-3+ gene was isolated by transformation of an aro-9 qa-2 cys-3 inl strain with a clone bank followed by screening with the "sib selection" method. The library used (pRAL1) contained inserts of Sau3a partial digest fragments of about 9 kilobases as well as the Neurospora qa-2+ gene. Double selection for qa-2+ and cys-3+ function was carried out. The transformants obtained with the isolated cys-3+ clone show recovery of the enzyme activities associated with the cys-3 mutation (e.g., arylsulfatase and sulfate permease). Restriction fragment length polymorphism experiments confirmed the identity of the clone, mRNA studies with Northern blots show that the expression of the cys-3+ gene is inducible. In contrast to cys-3+, the cys-3 (P22) mutant gene was not expressed at a higher level under sulfur-derepressed conditions. PMID- 2886910 TI - Mutagenic evaluation of etintidine (BL-5641), a novel histamine H2-receptor antagonist, using reverse mutation tests in bacteria and forward mutation tests in V79 Chinese hamster cells. AB - The mutagenic effects of etintidine (BL-5641), a novel histamine H2-receptor antagonist, were assessed using mutation in Salmonella typhimurium, Escherichia coli, and V79 Chinese hamster cells (V79 cells). Etintidine did not increase the revertant colonies in the presence or absence of S9 mix at concentrations from 5 to 5000 micrograms/plate in either of the bacterial tester strains. Etintidine also did not increase 6-thioguanine- and ouabain-resistant colonies in V79 cells in the presence or absence of S9 mix even at 37% cellular survival concentration. There was no evidence that etintidine had any mutagenic activity in any of the tests. PMID- 2886909 TI - Effects of intron length on differential processing of mouse mu heavy-chain mRNA. AB - Production of membrane-bound and secreted forms of mouse mu heavy-chain mRNA is controlled by differential processing in a developmental-stage-specific manner. We have analyzed the effects of various deletions and insertions in the C4-M1 intron of the mouse mu gene on the differential processing of mu mRNA. We show that there is a correlation between the length of the C4-M1 intron and the molar ratio of membrane-bound to secreted mu mRNAs, i.e., the shorter the C4-M1 intron, the higher the ratio. Since the poly(A) addition signal in the C4-M1 intron seems to be intact in the mutant mu genes, it is likely that the efficiency of splicing of the C4-M1 intron is affected by changes in the intron length. PMID- 2886911 TI - Purification, characterization, and kinetic analysis of inosine 5'-monophosphate dehydrogenase of Tritrichomonas foetus. AB - The IMP dehydrogenase of Tritrichomonas foetus, a parasitic protozoan incapable of de novo biosynthesis of purine nucleotides, has been purified about 1000-fold to apparent homogeneity. The purified enzyme demonstrated a 20-fold higher substrate turnover rate than the pure IMP dehydrogenase from sarcoma ascites tumor cells. It has a subunit molecular weight of 58,000, aggregates to a size of 380,000 at low ionic strength, and partly dissociates to a molecular weight of 270,000 in high salt concentrations. Unlike the IMP dehydrogenase of bacteria and mammals, the T. foetus enzyme does not require K+ for activity. The analysis of initial velocity and product inhibition data is consistent with a sequential, ordered bi bi kinetic mechanism for the parasite enzyme-catalyzed reaction, in which IMP binds before NAD+ and NADH is released before XMP. This is in contrast to the partially random mechanism of the bacterial enzyme which involves the formation of an enzyme-K+-(IMP) complex. Mycophenolic acid inhibits T. foetus IMP dehydrogenase uncompetitively versus both IMP and NAD+ with an apparent Ki of 9 microM. This value, which is several hundred-fold higher than that for mammalian IMP dehydrogenase, suggests significantly different binding properties of the mycophenolic acid site in T. foetus IMP dehydrogenase, which might be amenable to specific inhibitor design. PMID- 2886912 TI - DNA contents and molecular karyotypes of hybrid Trypanosoma brucei. AB - We have used restriction fragment length polymorphism markers to characterise parental and hybrid trypanosome stocks. Unexpected differences in the intensities of Southern hybridisation banding patterns led us to suspect that the hybrid organisms contained more DNA than the parental stocks. This has been confirmed using flow cytofluorimetry (FCF). Hybrids contained significantly more DNA than the parents, both as procyclic organisms (1.5 fold) and as bloodstream forms (1.5 1.6 fold). The DNA contents of both forms were stable through prolonged culture (procyclics), or serial passage (bloodstream forms), although limited data indicated that falls in DNA content could occur in bloodstream forms. FCF analysis of purified nuclei revealed that the increased DNA content of hybrids could be wholly ascribed to nuclear DNA. Our methods are able to detect hybrid organisms with elevated DNA contents in uncloned isolates following cyclical mixed transmission. We have used alternating field electrophoresis techniques to investigate whether the inheritance by the hybrids of the smaller chromosomes could account for their elevated DNA contents. Hybrids lacked the single 500 kb chromosome from one of the parents but appeared to have virtually double the amount of minichromosomes. However, this increase could only account for about 20% of the additional DNA. We are unable at present to distinguish between models for hybrid formation based on the fusion of predominantly diploid cells, and models in which the diploid chromosomes participate in conventional meiosis. PMID- 2886913 TI - Sulfasalazine and salicylate-induced exacerbation of ulcerative colitis. PMID- 2886914 TI - Host origin of marrow stromal cells following allogeneic bone marrow transplantation. AB - Although it is generally agreed that stromal cells are important in the regulation of haematopoietic cell development, the origin of these phenotypically diverse cells has been a subject for debate for more than 50 years. Data which support the concept of a separate origin for the haematopoietic stem cell and the marrow stroma are derived from cytogenetic or enzyme marker studies of explanted and expanded stromal cells grown under conditions that do not allow haematopoiesis in vitro. Recent evidence in man and in mouse suggesting that the stromal cells capable of transferring the haematopoietic microenvironment in vitro are transplantable seemingly questions this dichotomy, one interpretation being the existence of a common haematopoietic/stromal 'stem cell'. We used in situ hybridization to discriminate donor cells from host in blood and bone marrow samples obtained from patients with functioning sex-mismatched but HLA-identical allografts. Without exception, marrow-derived stromal cells that proliferate in long-term cultures were found to be of host genotype, whereas the macrophage component of the adherent layer in these cultures originated from the donor. PMID- 2886915 TI - Exchange of terminal portions of X- and Y-chromosomal short arms in human XX males. AB - In most human 'XX males', DNA sequences normally found on Yp, the short arm of the Y chromosome, are present on Xp, the short arm of the X chromosome. To establish whether this transfer involves a terminal portion of Yp, and whether a terminal portion of Xp is lost in the process, we followed the inheritance of pseudoautosomal restriction fragment length polymorphisms in two XX-male families. One XX male apparently inherited the entire pseudoautosomal region of his father's Y chromosome and no part of the pseudoautosomal region of his father's X chromosome. The second XX male also inherited the entire pseudoautosomal region of his father's Y, but in addition inherited a proximal portion of the pseudoautosomal region of his father's X. These findings argue that XX males result from the transfer of a terminal portion of Yp onto Xp in exchange for a terminal portion of Xp (ref. 7). This implies that the testis determining factor gene (TDF) maps distally in the strictly sex-linked portion of Yp, near the pseudoautosomal domain. The XX males described here appear to result from single (and, at least in the second case, unequal) crossovers proximal to the pseudoautosomal region on Yp and proximal to or within the pseudoautosomal region on Xp. PMID- 2886916 TI - Borders of parasegments in Drosophila embryos are delimited by the fushi tarazu and even-skipped genes. AB - One of the earliest molecular signs of segmentation in Drosophila embryos is the striped expression of some pair-rule genes during the blastoderm stage. Two of these genes, fushi-tarazu (ftz) and even-skipped (eve) are expressed during this stage in complementary patterns of seven stripes which develop and disappear in concert. Here, we map the cells expressing each of these two pair-rule genes with respect to the 14 stripes of cells expressing the engrailed gene. We find that both ftz and eve generate stripes which have sharp boundaries at the anterior margin, but fade away posteriorly. The anterior boundaries correspond cell by cell with the anterior boundaries of expression of the engrailed gene. We therefore suggest that a key function of early ftz and eve gene activity is the formation of a sharp stable boundary at the anterior margin of each stripe. These boundary lines, rather than the narrowing zonal stripes, would delimit the anterior boundaries of engrailed and other homoeotic genes and thereby subdivide the embryo into parasegments. PMID- 2886917 TI - A linked genetic marker for multiple endocrine neoplasia type 2A on chromosome 10. AB - Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominantly inherited cancer syndrome characterized by medullary carcinoma of the thyroid, phaeochromocytoma and hyperparathyroidism. Almost all gene carriers can be detected by screening tests before the age of 40, but the nature and location of the predisposing gene are unknown. Simpson et al. recently reported preliminary evidence for linkage between the DNA probe p9-12A on chromosome 10 and MEN2A. We now report linkage between the MEN2A locus and the interstitial retinol-binding protein gene, which is located on chromosome 10p11.2-q11.2. PMID- 2886918 TI - Assignment of multiple endocrine neoplasia type 2A to chromosome 10 by linkage. AB - Multiple endocrine neoplasis type 2A (MEN2A) is one of several kinds of cancers that appear to be inherited in an autosomally dominant fashion. We have assigned the MEN2A locus to chromosome 10 by linkage with a new DNA marker (D10S5). The linkage led us to investigate other chromosome 10 markers and demonstrate linkage between the disease locus and the interstitial retinol-binding protein (IRBP) gene. The D10S5 locus was sublocalized to 10q21.1 by hybridization in situ and the IRBP gene to p11.2----q11.2 with a secondary site at q24----q25. The linkages were established using 292 members of five families, three different restriction fragment length polymorphisms (RFLPs) at D10S5 and two RFLPs recognized by the IRBP probe. The recombination frequencies from pairwise linkage analysis between the disease and two marker loci D10S5 and IRBP were 0.19 and 0.11, with maximum lod scores of 3.6 and 8.0 respectively. Ordering of the three loci by multipoint analysis placed the IRBP gene approximately midway between the disease and D10S5 loci. PMID- 2886919 TI - Chromosome 5 allele loss in human colorectal carcinomas. AB - That the sporadic and inherited forms of a particular cancer could both result from mutations in the same gene was first proposed by Knudson. He further proposed that these mutations act recessively at the cellular level, and that both copies of the gene must be lost for the cancer to develop. In sporadic cases both events occur somatically whereas in dominant familial cases susceptibility is inherited through a germline mutation and the cancer develops after a somatic change in the homologous allele. This model has since been substantiated in the case of retinoblastoma, Wilms tumour, acoustic neuroma and several other tumours, in which loss of heterozygosity was shown in tumour material compared to normal tissue from the same patient. The dominantly inherited disorder, familial adenomatous polyposis (FAP, also called familial polyposis coli), which gives rise to multiple adenomatous polyps in the colon that have a relatively high probability of progressing to a malignant adenocarcinoma, provides a basis for studying recessive genes in the far more common colorectal carcinomas using this approach. Following a clue as to the location of the FAP gene given by a case report of an individual with an interstitial deletion of chromosome 5q, who had FAP and multiple developmental abnormalities, we have examined sporadic colorectal adenocarcinomas for loss of alleles on chromosome 5. Using a highly polymorphic 'minisatellite' probe which maps to chromosome 5q we have shown that at least 20% of this highly heterogeneous set of tumours lose one of the alleles present in matched normal tissue. This parallels the assignment of the FAP gene to chromosome 5 (see accompanying paper) and suggests that becoming recessive for this gene may be a critical step in the progression of a relatively high proportion of colorectal cancers. PMID- 2886920 TI - Major histocompatibility complex class I molecules internalized via coated pits in T lymphocytes. AB - Endocytosis of the major histocompatibility complex (MHC)-encoded class I and class II molecules has been the subject of recent investigations. Class I molecules, which are key elements in T cell-mediated cytotoxicity, are differentially endocytosed by different cell types. Fibroblasts internalize their class I molecules via uncoated cell surface vesicles and tubular invaginations when these molecules are cross-linked with multivalent ligands. T lymphocytes internalize their class I molecules spontaneously, but B lymphocytes do not internalize them at all. Here we describe a morphological investigation of the mechanism by which class I molecules are endocytosed by T lymphocytes. We show that, unlike fibroblasts, T lymphocytes spontaneously internalize 20-40% of their class I molecules in a process involving coated pits and coated vesicles. Thus, the endocytic pathway of class I molecules in T lymphocytes is similar to those of other more classical cell-surface receptors involved in receptor-mediated endocytosis. In contrast, the same class I molecules remained on the cell surface in B lymphocytes. These data show that class I molecules are differentially regulated in T and B lymphocytes and fibroblasts. PMID- 2886921 TI - Effects of acute continuous exposure of the rat to cigarette smoke on amine levels and utilization in discrete hypothalamic catecholamine nerve terminal systems and on neuroendocrine function. AB - The effects of acute continuous exposure to the smoke from 1-4 cigarettes have been studied in the male rat in terms of hypothalamic catecholamine levels and utilization as well as the secretion of anterior pituitary hormones. Catecholamine levels in discrete hypothalamic catecholamine nerve terminal systems were studied by quantitative histofluorimetry. Catecholamine utilization was studied by means of the tyrosine hydroxylase inhibition method using alpha methyl-(+/-)-p-tyrosine methyl ester. The serum hormone levels of adenohypophyseal hormones and of corticosterone were measured by the use of radioimmunoassay procedures. The results show that acute continuous exposure to unfiltered but not to filtered (Cambridge glass fibre filters) cigarette smoke leads to small but dose-dependent reductions of amine levels in most of the hypothalamic noradrenaline and dopamine nerve terminal system. These effects were associated with an enhancement of regional hypothalamic noradrenaline utilization but not of dopamine utilization in the median eminence. Furthermore, a reduction of TSH and prolactin serum levels was noted as well as increases in ACTH secretion. These results are partly different from those previously obtained with rats acutely exposed to intermittent unfiltered cigarette smoke. This difference is suggested to be due to a temporary blockade of catecholamine release following acute continuous exposure to cigarette smoke. PMID- 2886922 TI - Rapid and reversible desensitisation of vascular and platelet alpha 2 adrenoceptors. AB - The effects of intravenous infusion with the alpha2 adrenoceptor selective agonist alpha methylnoradrenaline on pressor responses to alpha adrenoceptor agonists, alpha2 adrenoceptor mediated platelet aggregation and adenylate cyclase were examined in conscious rabbits. Pressor responses to alpha methylnoradrenaline but not phenylephrine were decreased in a dose dependent manner during methylnoradrenaline infusion at all times examined. Recovery of these responses after stopping infusion was dependent on both the dose infused and the duration of the infusion. Alpha methylnoradrenaline infusion resulted in a dose and time dependent decrease in the pro-aggregatory response of platelet to adrenaline without any significant change in the response to ADP or in the number of [3H]yohimbine binding sites. The ability of PGE1 to stimulate adenylate cyclase was not influenced by alpha methylnoradrenaline infusions. However, reversal of this stimulation by adrenaline was decreased by relatively long (30 min) infusions of the highest dose of alpha methylnoradrenaline examined. It is concluded that alpha methylnoradrenaline infusions resulted in desensitisation of all the alpha2 adrenoceptor mediated responses examined. However the time course for the desensitisation apparently differed according to the response examined. PMID- 2886923 TI - The role of cyclic AMP in the positive inotropic effect mediated by beta 1- and beta 2-adrenoceptors in isolated human right atrium. AB - The time course of the effects of isoprenaline (3 X 10(-7) mol/l) on contractile force and on the cyclic AMP level was studied in the electrically driven isolated muscle strip of the human right atrium. Isoprenaline produced a rise in cyclic AMP content (maximum increase after 60 s) preceding the increase in contractile force. The effects of isoprenaline on contractile force and on the intracellular level of cyclic AMP were enhanced in the presence of the phosphodiesterase inhibitor papaverine (10(-5) mol/l). On the other hand, the beta-adrenoceptor antagonist propranolol (10(-7) mol/l) suppressed isoprenaline-induced cyclic AMP increases, but reduced the increase in force of contraction by only 35%. In addition, both the beta 1-selective antagonist bisoprolol (3 X 10(-9)-3 X 10(-8) mol/l) and the beta 2-selective antagonist ICI 118,551 (3 X 10(-9)-3 X 10(-8) mol/l) inhibited the isoprenaline-induced cyclic AMP increase concentration dependently; ICI 118,551 produced more pronounced inhibition than bisoprolol. It is concluded that cyclic AMP is involved in the positive inotropic action of isoprenaline evoked by beta 1- and beta 2-adrenoceptor stimulation in isolated human right atrium; however, an additional cyclic AMP independent mechanism cannot be ruled out. PMID- 2886924 TI - Palytoxin-induced endothelium-dependent relaxation in the isolated rat aorta. AB - The effects of a potent marine toxin, palytoxin (PTX), were investigated on the contractile responses in the isolated rat aorta with or without endothelium. PTX in the concentrations of 10(-13)-10(-11) mol/l showed little effect on the resting tension of the vessel with or without endothelium. PTX, 10(-10) mol/l, induced a small contraction in the aorta without endothelium but not in the aorta with endothelium. When added during the sustained contraction induced by 10(-7) mol/l norepinephrine, 10(-12) mol/l PTX sometimes (6 out of 43 strips) augmented the norepinephrine-induced contraction whereas 10(-11)-10(-10) mol/l PTX induced a biphasic response which was composed of a transient augmentation followed by a relaxation. These effects of PTX were not observed in the aorta without endothelium. Influences of atropine (10(-6) mol/l), indomethacin (2.5 X 10(-5) mol/l), methylene blue (5 X 10(-6) mol/l), hydroquinone (10(-4) mol/l), phenidone (5 X 10(-5) mol/l), hemoglobin (10(-6) mol/l) and p-bromophenacyl bromide (5 X 10(-5) mol/l) on the PTX (10(-10) mol/l) induced responses were examined. Methylene blue, hydroquinone, phenidone, hemoglobin and p-bromophenacyl bromide inhibited both the PTX-induced augmentation and relaxation of the norepinephrine induced contraction. The endothelium-dependent relaxation due to 3 X 10(-7) mol/l carbachol was inhibited by atropine, methylene blue, hydroquinone, phenidone, hemoglobin and p-bromophenacyl bromide. These results suggest that PTX acts on the endothelium, modifies the synthesis or release of endothelium-derived relaxing factor and thus changes the contractile response to norepinephrine in rat aorta. PMID- 2886926 TI - Buspirone. Just another antianxiety agent? PMID- 2886925 TI - Piperazine derivatives including the putative anxiolytic drugs, buspirone and ipsapirone, are agonists at 5-HT1A receptors negatively coupled with adenylate cyclase in hippocampal neurons. AB - Two putative anxiolytic drugs [ipsapirone (TVXQ 7821) and buspirone], structurally unrelated to benzodiazepines, have negligible ataxic and sedative side effects. These drugs are piperazine analogs which interact at 5-HT1 binding sites. It is demonstrated here that these drugs and two other piperazine derivatives, trifluoromethylphenylpiperazine (TFMPP) and m-chlorophenylpiperazine (mCPP), are agonists at 5-HT1A receptors, a subclass of the 5-HT1 receptor, mediating inhibition of forskolin (100 microM) stimulated adenylate cyclase in particulate fractions of guinea pig hippocampus as well as inhibition of the formation of cyclic AMP promoted by vasoactive intestinal polypeptide (0.1 microM) plus forskolin (1 microM) in mouse hippocampal neurons in primary culture. This study demonstrates that these piperazine based drugs act in both brain homogenate preparations and in intact neurons in a similar manner. The biochemical models described here may aid in the development of even more active drugs in this class. PMID- 2886927 TI - [Antiemetics]. PMID- 2886928 TI - [The use of kits in the diagnosis of infections]. PMID- 2886930 TI - [Salazosulfapyridine or 5-aminosalicylic acid]. PMID- 2886929 TI - [The maintenance dosage of neuroleptic agents]. PMID- 2886931 TI - [Analysis of the effect of glutamic acid diethyl ester on synaptic processes in the ampullae of Lorenzini of the skate]. AB - The effects of glutamic acid diethylester (GDEE) on the electrical activity of the ampullae of Lorenzini were studied in skates. GDEE (10(-6)-10(-4) M) caused a decrease in frequency of afferent discharges in all receptors under study. GDEE also reversibly blocked the effects of excitatory amino acids (L-glutamate and L aspartate). The results suggest that L-glutamate or related substance is likely to be the synaptic transmitter in the ampullae of Lorenzini. PMID- 2886932 TI - [Neuroleptic-related admissions to a university psychiatric clinic]. PMID- 2886934 TI - Neuroanatomical substrate for the inhibition of gonadotrophin secretion in goldfish: existence of a dopaminergic preoptico-hypophyseal pathway. AB - To investigate the existence of a dopaminergic preoptico-hypophyseal pathway in the goldfish, electrolytic lesions were placed in the rostral preoptic area and their effects on gonadotrophin levels and pituitary innervation examined. In a first experiment, the fish were sacrificed 2 days after surgery and the pituitary studied by electron microscopy. Numerous exocytosis profiles were observed in the gonadotrophs, confirming the large increase in serum gonadotrophin levels measured in the animals. In addition, type A and B degenerating fibers were detected in the neurohypophysis and the pars distalis, in particular at the level of the gonadotrophs. In the second experiment, the distribution of tyrosine hydroxylase-immunopositive fibers was studied in the pituitary of controls and lesioned animals. It was found that lesioning the anterior ventral preoptic region resulted in the disappearance of all positive fibers in the pars distalis, while those in the neurointermediate lobe appeared unaffected. The presence of a large group of catecholaminergic perikarya in the destroyed area was confirmed in control animals. These results and other data strongly support the existence of a dopaminergic preoptico-hypophyseal pathway, providing a morphological support for the inhibitory effect of dopamine on the release of anterior pituitary hormones in teleosts, in particular gonadotrophin. PMID- 2886933 TI - Differential binding of somatostatin agonists to somatostatin receptors in brain and adenohypophysis. AB - In order to improve our understanding of the ligand specificity of somatostatin (SRIF) receptors in pituitary and brain, and to identify analogs that bind to one type exclusively, we compared several new SRIF analogs for competitive binding to pituitary and cerebral cortex membranes. Binding of [125I-Tyr11]SRIF to hypophysis and brain was of high affinity [KD = 0.76 nM (0.2-1.3) and 0.37 nM(0.1 0.8), mean (95% confidence limits)] and was characteristic of binding to one class of sites in both tissues. Competition by several SRIF analogs for such radioligand binding demonstrated that ligand specificity of adenohypophysial receptors was distinctly different from that of cerebral cortex. Two cyclic octapeptides (sequence; see text) bound to pituitary SRIF receptors with high affinity [Ki = 0.85 nM (0.5-1.2) and 0.35 nM (-0.3-0.9)] and were potent inhibitors of GH secretion from primary cultured pituitary cells [EC50 = 0.009 nM (0-0.02) and 0.017 nM (0.01-0.02), respectively]. However, these selective peptides did not compete (Ki much greater than 1 microM) for radioligand binding to brain. Amidation of the C-terminal end appeared to strikingly alter brain SRIF receptor recognition of the substituted ligand. Indeed, such amidation of the parent peptide, (sequence; see text) resulted in a reduced ability to displace labeled ligand from brain sites [Ki = 165.3 nM (47.6-282.9) to 842.2 nM (603.9 1,081)] but did not affect competition for pituitary receptors. Our results indicate that anterior pituitary SRIF receptors (SRIFa) have ligand specificities which are clearly different from those of their brain counterparts (SRIFb).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2886937 TI - Stereotactic mesencephalic tractotomy for thalamic pain. AB - Forty years after its first reported use, stereotactic mesencephalic tractotomy remains effective in relieving thalamic pain. Twenty seven patients suffering central pain following cerebrovascular accidents were treated by this operation and twenty four were reviewed: sixteen (66.7%) reported long term relief. Fourteen underwent surgery at the original 'superior colliculus' target, nine out of twelve (75%) reporting significant relief. Thirteen had surgery at a revised 'inferior colliculus' target, seven out of twelve (58.3%) obtaining relief. Postoperative disorders of ocular movement were reduced from 83.3% to 20%, and significant problems of binocular vision from 50% to nil. The mortality rate was 7.4%. PMID- 2886935 TI - Possible role of alpha-2-noradrenergic receptors in modulation of sexual behavior in female guinea pigs. AB - These studies examine whether alpha 1-noradrenergic receptor stimulation alone is sufficient to facilitate lordosis behavior in ovariectomized, estrogen-primed female guinea pigs and to what extent alpha 2-noradrenergic receptors are involved in this steroid-dependent behavior. Neither of the alpha 1-agonists, phenylephrine or methoxamine, significantly facilitated lordosis in ovariectomized females primed with 10 micrograms of estradiol benzoate for 1 or 3 days. Animals exhibiting estrogen plus clonidine-facilitated lordosis showed a decrease in the behavior when given one of two alpha 2-antagonists (yohimbine or idazoxan). Idazoxan also attenuated lordosis in animals given estrogen plus progesterone. These findings, in combination with previous findings (that specific alpha 1-antagonists block lordosis), suggest that alpha 2-receptors, in addition to alpha 1-receptors play a role in modulation of lordosis behavior. PMID- 2886936 TI - Delta sleep inducing peptide inhibits somatostatin release via a dopaminergic mechanism. AB - Delta sleep inducing peptide (DSIP) has been localized in the rat hypothalamus. The effect of DSIP on somatostatin (SRIF) release from the median eminence of the hypothalamus was evaluated in male and female rats in an in vitro incubation system. DSIP inhibited SRIF release in a dose-dependent manner. The median eminences from females were less sensitive to the inhibitory action of DSIP than those of males; however, in both sexes the maximum effect was observed at a concentration of 10(-8) M DSIP. This effect was blocked by addition of pimozide at a concentration of 10(-6) M. Pimozide alone had no effect on SRIF release. These findings lead to the conclusion that DSIP inhibits SRIF release via a dopaminergic mechanism. PMID- 2886938 TI - Microelectrode techniques in localization of stereotactic targets. AB - Although physiological corroboration of the target is essential in functional stereotactic surgery, the collected data can also be used for the offline study of normal and abnormal brain function. Such studies have the advantage of being made in actual clinical states with the unique opportunity of communicating with the patient. Correlations were made between microelectrode recordings and microstimulation at the same thalamic site with the same microelectrode in 'normal' patients, in those with tremor and in those with central and deafferentation pain. Human somatosensory organization is similar to that of subhuman primates. Five types of tremor cells have been identified-unresponsive nonsynchronous, unresponsive synchronous, kinaesthetic, voluntary, and voluntary with receptive field. While the last two qualify in latency and connectivity as tremor pacemakers, system analysis suggests an important element of long loop feedback as well. In the pain patients, five features were identified-somatotopic reorganization, altered firing in reorganized cells, bursting cells induction of burning widespread in thalamus and reproduction of the patient's pain by microstimulation-possibly a 'central allodynia' found in deafferented somatosensory thalamus particularly in patients with allodynia or hyperpathia. All but the latter effects may be merely the consequence of deafferentation and were seen in a 'control' stroke patient with dystonia, sensory loss but no pain. PMID- 2886939 TI - Pontine stereotactic surgery and facial nociception. AB - Pontine stereotactic tractotomy was performed on 13 patients for the relief of intractable pain. The results of electrical stimulation performed to localise target sites and confirm electrode trajectory are described. Stimulation sites included the cerebellum, cerebellar peduncle, trigeminal nucleus, facial nucleus, cochlear and vestibular nuclei and the trigeminal descending quintothalamic and spinothalamic tracts. Particular attention was given to facial sensory responses. Stimulation of the trigeminal nucleus produced discrete sensations, but quintothalamic stimulation gave more general ipsilateral facial sensation. Medullary trigeminal nucleotomy is recommended for facial deafferentation pain because it interrupts intranuclear trigeminal connections in the caudal trigeminal nucleus where the point of neuronal hyperactivity and stimulus convergence lies. PMID- 2886940 TI - Stereotactic software for the GE 8800 CT scanner. AB - A computer software program (Seapit) was developed for precise determination of intracranial targets identified by stereotactic computed tomography (CT). This program was added to the software of a GE 8800 CT scanner to perform the following operations: millimetre precise calculation and display of the rectilinear coordinates of a target identified on axial CT images; preplotting of phantom target trajectories on the CT images or electronic radiographs; calculation of probe angles required to achieve various trajectories; display of a coordinate scale on each CT image to allow direct target determination without mathematical calculations; calculation of the intercommissural plane for functional neurosurgery. In a series of 100 patients undergoing stereotactic surgery, the Seapit program proved to be a superior and accurate method of target coordinate calculation. Preview display on the CT images of 'phantom' probes significantly enhanced the safety of stereotactic intervention. PMID- 2886941 TI - Application of robotics to stereotactic neurosurgery. AB - Advances in the field of stereotactic neurosurgery have depended on improvements in brain-imaging techniques, as well as development of new stereotactic frame systems. This paper describes the development of a stereotactic system based on a robotics model. The system employs the Unimation Puma Mark II Robotic System, specifically modified for use in stereotactic surgery. The robotic CT stereotactic system is mounted in a dedicated operating suite, containing a CT scanning gantry and adjacent computer room. Stereotactic coordinates are derived from CT scan data obtained intraoperatively and transferred by computer link to the robotic stereotactic system. The robotic arm is driven into place to align with predetermined coordinates. A variety of stereotactic procedures may then be carried out using the robotic 'hand' as a guide to the target. So far, the device has been used, only for lesion biopsy. However, future applications to functional neurosurgery are anticipated. PMID- 2886942 TI - Stereotactic clipping of arteriovenous malformations of the brain. AB - The authors have developed a new technique for the stereotactic clipping of the feeding vessels of deep-seated arteriovenous malformations (AVM), for use when direct attack may be very dangerous or impossible. A special clipping device and the technique for its application are described. The instrument is introduced through a burr hole using the stereotactic apparatus designed by the authors. The clipping is monitored by intraoperative angiography. The method was used in 32 patients with supratentorial AVMs. It is concluded that in selected cases the method is effective, is less traumatic and gives successful results. PMID- 2886943 TI - Noninvasive multipurpose stereoadapter. AB - A noninvasive adapter for stereotaxis guided by computed tomography and magnetic resonance imaging, which was originally developed for morphological (tumour biopsy) surgery, has also been used for functional stereotaxis (thalamotomy, cingulotomy, hypothalamotomy, dentatotomy, etc.), for stereotactic angiography and for external stereotactic irradiation of brain tumours with a conventional linear accelerator. In addition, it has been applied to the location of subcortical brain tumours for open surgery. Recently, the stereoadapter has been supplied with a phantom base, which permits percutaneous tumour biopsy and ventriculostomy without a stereotactic frame. PMID- 2886944 TI - Leksell stereotactic radiosurgery in the treatment of eye melanoma. AB - Current experiments indicate that a focussed single radiation treatment with a dose of 6000 to 9000 rads delivered to the 90% zone through a collimator of the Leksell stereotactic radiosurgical unit or 'gamma knife' to the rabbit eye melanoma model is capable of destroying the cancer totally and thus effecting a cure. The beneficial effect in these rabbit eye melanoma experiments appears to be similar to the results obtained by physicians using the Harvard and Berkeley cyclotrons in treating malignant neoplasms in the human eye. Therefore, it is proposed that a properly designed stereotactic radiosurgical unit can be used in patients with eye tumours similar to those selected for the cyclotron systems. PMID- 2886946 TI - Stereotactic radiosurgery. Present status and future trends. AB - Stereotactic radiosurgery was introduced by Lars Leksell in 1951, as a means of treating a variety of intracranial pathologies without opening the skull. Since 1968 the radiosurgical procedures have been performed in the Leksell Gamma Unit. The number of conditions amenable to this treatment modality has constantly increased and today about 1500 patients have been treated in Stockholm. The radiosurgical technique, some of the indications for radiosurgery as well as the clinical results are reviewed. PMID- 2886945 TI - Stereotactic catheter insertion: a new technique. AB - In spite of modern instrumentation that is widely available, inaccurate and even crude techniques are still occasionally used for puncturing cavities within the cranial cavity. Thus, a standardized technique for intracranial puncturing, based on stereotaxy, is suggested and illustrated by some clinical cases. PMID- 2886947 TI - Stereotactic biopsy and brachytherapy of brain tumours. AB - This paper discusses 98 patients who had their cerebral lesions stereotactically biopsied. Modified Riechert-Mundinger instrumentation was employed. Of the 98 patients, eight received only biopsy and 90 were then interstitially radiated with iridium-192 (192Ir) custom stacked in afterloading catheters. The vast majority of brachytherapeutically treated lesions were anaplastic or malignant astrocytomas. There were some metastatic lesions, and in two instances the tumour occupied the infratentorial compartment. Two-thirds of the patients had received prior teletherapy; in the remainder, stereotaxis provided the initial diagnosis and brachytherapy the principal treatment. The survival data suggest reasons for optimism. Eighty percent of patients with anaplastic astrocytoma were alive 2 yr later, compared with 55% for those harbouring malignant astrocytomas. Since this is the largest database on this topic in the U.S.A., we are in the process of a more critical review. Complication rate is low. Diagnostic tissue was obtained in all instances. Delayed radionecrosis at the site of implant may aggravate neurological deficits when lesions involve functionally sensitive cortex or their pertinent underlying structures. Such reactions may appear 4-18 mnth after brachytherapy and are more likely to occur in patients who were previously radiated. PMID- 2886948 TI - Interstitial radiobrachytherapy of malignant cerebral neoplasms: rationale, methodology, prospects. AB - The local use of radionuclides in the management of neoplastic processes was initially considered over 80 yr ago and has enjoyed increasing enthusiasm in the treatment of somatic and central nervous system tumours during the past 30 yr. The marriage of complex neuroimaging techniques and modern stereotactic devices has markedly enhanced the technical precision of interstitial radiobrachytherapy of malignant cerebral neoplasms. In applying these techniques, it is imperative to achieve an optimal placement of radionuclide sources in order to develop a geometrically homogenous, controlled distribution of radiation. Critical considerations include determination of tumour volume and contour, and development of a homogenous dose rate (dependent upon multiple sources at varying intensity) that will not only effect tumour cell kill but do this without excessive production of radionecrosis which necessitates craniotomy because of mass. Using the Brown-Roberts-Wells (BRW) stereotactic guidance system and an image-defined, volumetrically determined target, implants of multiple iridium 192(192Ir) sources were used to establish appropriate isodose envelopes. A methodology for achieving the described objectives is detailed as it applies to a variety of malignant intracerebral neoplasms (glioblastoma multiforme, malignant astrocytoma, malignant mixed glioma, primary cerebral lymphoma, metastatic carcinoma and malignant pineal region tumours). Technical realization of precision implantation relying upon imaging data may be acheived with this method with satisfactory responses that are dependent upon histological tumour type and the morphology of the tumour distribution as related to the image. Early and late complications related to the surgical technique and radionuclide applications were less than 5%. Although encouraging, these techniques require further definition and greater data accrual before uniform application outside major medical centres can be justified. It is anticipated that improvement in results with intrinsic gliomas and other invasive neoplasms will be realized with further definition of tumour boundaries by tract biopsy techniques and concurrent utilization of hyperthermia and brain protective methods. PMID- 2886949 TI - Characterization of pre- and postjunctional receptors for neurokinins and kinins in the rat vas deferens. AB - Neurokinins and kinins are potent stimulants of the rat vas deferens: they increase both the twitch response to electrical stimulation by facilitating transmitter release and the basal tone of the preparation by activating smooth muscle receptors. The two sites of action have been studied separately in the present experiments by using the prostatic for the prejunction site and the epididymal section of the vas deferens for the postjunction site. Receptors for neurokinins, characterized by the order of potency of agonists, appear to be of the NK-A type both at the pre- and postjunction level. Receptors for kinins are present also at both sites and are probably of the B2 type: they have been characterized by the use of agonists and, the B2 postjunction type has been convalidated with antagonists. These compounds could not be used for the prejunction receptor characterization, because they act as agonists. Receptor for angiotensin at the prejunction level are of the same type as in the cardiovascular and other systems. PMID- 2886950 TI - Specific inhibitors of pyroglutamyl peptidase I and prolyl endopeptidase do not change the in vitro release of TRH or its content in rodent brain. AB - Pyroglutamyl diazomethyl ketone and N-benzyloxycarbonyl prolyl prolinal, specific inhibitors of pyroglutamyl peptidase I and prolyl endopeptidase respectively, were used to study the possible role of these enzymes in the regulation of thyrotropin releasing hormone turnover. In vitro thyrotropin releasing hormone release by male rat hypothalamic slices was studied. Combined in vitro treatment with 10(-5)M of both inhibitors totally inhibited both enzymatic activities. The treatment did not affect basal or 56 mM K+ induced thyrotropin releasing hormone release or thyrotropin releasing hormone levels in slices. Repeated combined intraperitoneal injections of the two inhibitors for up to 12 hours produced a 70%-95% reduction in mouse brain pyroglutamyl peptidase I specific activity and a 65%-85% reduction in prolyl endopeptidase specific activity. Thyrotropin releasing hormone levels were unaffected by this treatment in all regions tested. The data suggest that these two enzymes are not involved in the intra- or extracellular control of thyrotropin releasing hormone levels in brain or hypophysis. PMID- 2886951 TI - Use of psychotropic drugs in general medical geriatric inpatients. Relationship with various parameters of psychological distress (evaluated 'in blind'). AB - The authors have evaluated the psychotropic drug use patterns and psychological distress (with the Symptom Distress Checklist, SCL-90) amongst 331 elderly medical inpatients. Forty-two percent of the sample took psychotropic drugs during their hospitalization period. The drugs most commonly used were anxiolytics and hypnotics of the benzodiazepine class. Subjects to whom psychotropic drugs were prescribed reported higher psychological distress compared to those not receiving them; however, a score of moderate distress in the depression and sleep disturbances subscales was reported by a relatively high percentage of subjects not receiving psychotropics. Patients taking antidepressants reported scores of psychological suffering higher than those under benzodiazepine treatment: such a difference not only related to the depression subscale, but to the majority of the symptom areas investigated by the SCL-90. PMID- 2886952 TI - Comparative study of four evaluation criteria in a clinical trial with schizophrenic patients. AB - In order to compare the level of agreement between four evaluation criteria, data from an 18-month clinical trial with 181 schizophrenic patients were reanalyzed. In that study, assessments of the subjects were carried out with two psychiatric rating scales, Brief Psychiatric Rating Scale and Nurses' Observation Scale for Inpatient Evaluation (BPRS and NOSIE), and two clinical evaluations (psychiatrist and nurse). Results show that there was total agreement on the four outcome measures for only half of the subjects. After further analyses, we observed that the best agreement was between the two clinical assessments. The NOSIE had poor agreement with the other criteria and appeared less sensitive to moderate levels of improvement in the patients' clinical status. These results are discussed with respect to reliability and validity issues. PMID- 2886953 TI - Classification of psychotropic drugs by rat EEG analysis: learning set development. AB - EEG recordings from 5 different brain areas of freely moving rats were performed under controlled vigilance stage conditions. Effects of antidepressant and neuroleptic drugs were assessed following their intraperitoneal injection. Quantification of the drug effects was achieved by analysis of variance following on-line fast-Fourier transformation of the EEG signal. This resulted in so-called drug profiles. From the individual antidepressant and neuroleptic drug profiles, an antidepressant and neuroleptic drug class profile was calculated. Using the absolute power for the calculation of the antidepressant and neuroleptic drug class profiles gave a better discrimination between the two drug class profiles than using the relative power. The antidepressant and neuroleptic drug class profiles derived from the n. amygdala and hippocampus did not show significant differences. The antidepressant and neuroleptic drug class profiles showed significant differences (p less than 0.05) in rather small frequency bands from the n. caudatus (16-14 Hz), n. accumbens septum (19-24 and 27-31 Hz) and cortex (10-20 Hz). PMID- 2886954 TI - MR brain scanning in patients with vasculitis: differentiation from multiple sclerosis. AB - We performed MR (magnetic resonance) brain imaging on 24 patients with a systemic vasculitis. MRI proved to be a sensitive method for detecting brain lesions (clinically silent or manifest) in these patients. The most frequent abnormalities were periventricular lesions seen in 12 cases. Such changes are not specific for vascular disease, and are often seen in multiple sclerosis. However, additional changes were commonly seen which suggested the correct diagnosis. PMID- 2886955 TI - Pharmacological study of the cortical-induced excitation of subthalamic nucleus neurons in the rat: evidence for amino acids as putative neurotransmitters. AB - Extracellular records were made from subthalamic nucleus neurons during microiontophoretic application of drugs and stimulation of the corticosubthalamic nucleus pathway. In 87% of the subthalamic nucleus cells, cortical stimulation induced a powerful excitation, consisting of a burst of 1-7 spikes. This projection must arise from a large area of the cortex since stimulation of nearly all the ipsilateral cortex and the rostral two-thirds of the contralateral cortex was found to influence the activity of subthalamic nucleus neurons. Experiments were undertaken in order to determine the identity of the neurotransmitter involved in the corticosubthalamic nucleus pathway. Glutamic acid diethyl ester reversibly suppressed subthalamic nucleus excitations induced by ipsi- or contralateral cortical stimulation or microiontophoretically applied glutamate. On the same cells, this compound had no effect on acetylcholine-evoked excitation and gamma-aminobutyric acid-evoked inhibition and subthalamic excitation induced by stimulation of the tegmenti pedunculopontine nucleus. Atropine at doses which antagonized the acetylcholine response, flupenthixol at dose which antagonized the dopamine response, and bicuculline at doses which antagonized the gamma aminobutyric acid response failed to block excitations evoked by cortical stimulation and by glutamate. These experiments excluded a role for acetylcholine, dopamine and gamma-aminobutyric acid in the cortically evoked excitation of subthalamic nucleus cells. Since an amino acid seemed to play a role as neurotransmitter of the corticosubthalamic nucleus pathway, further experiments were designed to confirm these data and to determine the contribution of each amino acid receptor type in the cortical-induced excitation of subthalamic cells. All the subthalamic cells recorded were also excited by microiontophoretically applied N-methyl-D-aspartic, quisqualic and kainic acids. The cortical-evoked activation of subthalamic nucleus neurons was reversibly suppressed by kynurenic acid and cis-2,3-piperidine dicarboxylic acid, two broad spectrum antagonists of excitatory amino acids, microiontophoretically applied at doses which also blocked excitations induced by N-methyl-D-aspartic, quisqualic and kainic acids. Application of 2-amino-5-phosphonovaleric acid inhibited excitation induced by N-methyl-D-aspartic acid but not those elicited by quisqualic or kainic acid, while glutamate excitation was only slightly affected. This compound had no effect on the cortically evoked excitation of subthalamic nucleus neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2886956 TI - Daily variations in monoamine turnover in the brain of the ring dove (Streptopelia risoria). AB - A method for measuring the concentration and turnover of serotonin, dopamine and noradrenaline in small amounts of brain tissue was validated for the ring dove (Streptopelia risoria). Turnover rates of the catecholamines calculated as the rate of depletion after tyrosine hydroxylase inhibition agreed well with turnover rate measured as rate of accumulation after inhibition of monoamine oxidase at 2.5 h, but not 5 h, after drug administration. Using the monoamine oxidase inhibitor, pargyline, turnover of serotonin, dopamine and noradrenaline were estimated in the same tissue. Both the concentration and turnover of the amines in hypothalamus, paleostriatum and hyperstriatum fluctuated over a 24 h period. Serotonin turnover was greatest during the middle of the dark period in all three tissues. In contrast, for both dopamine and noradrenaline the highest turnover was observed during the light period and the lowest during the dark period. PMID- 2886957 TI - [Somatostatin in the treatment of bleeding esophageal varices. Our experience]. PMID- 2886958 TI - Microscopic polyarteritis: recovery of renal function after prolonged dialysis. PMID- 2886959 TI - Identification of somatostatin-containing neurons in primary cultures of rat cerebral cortex. AB - The expression of somatostatin-like immunoreactivity was investigated in primary cultures of dissociated cerebral cortical tissue from the rat. A subpopulation of neurons in the cortical cultures exhibited intense staining for somatostatin. These somatostatin-immunoreactive neurons corresponded to 1.25% of the total neuronal population. Stained neurons were typically small with a soma size of 10 20 micron. The majority of somatostatin-containing cells had stellate and bipolar morphology, with the bipolar class predominating. PMID- 2886960 TI - Co-localization of neuropeptide tyrosine and somatostatin immunoreactivity in neurons of individual subfields of the rat hippocampal region. AB - The co-localization of neuropeptide tyrosine (NPY) and somatostatin (SOM) in rat hippocampal cells was studied in double labelling experiments using a combination of antibodies against the two peptides on the same tissue section. The individual hippocampal subfields show large variations in the relative number of NPY- and SOM-immunoreactive (-i) neurons. While the entorhinal area is far richer in SOM as compared to NPY-i cells, NPY-i cells predominate in all subfields (e.g. regio superior, regio inferior) of Ammon's horn. Co-localization of both peptides in single neurons was highest in regio inferior and in the area dentata and lowest in the retrohippocampal structures. In the dorsal hippocampus, the number of SOM i cells containing NPY-i was higher than the number of NPY-i cells containing SOM i. This pattern was reversed in the retrohippocampal region. At ventral levels the incidence of colocalization of NPY- and SOM-i in single cells increased in all hippocampal subfields. PMID- 2886962 TI - Hyperpolarizing responses to application of glutamate in hippocampal CA1 pyramidal neurons. AB - Micropressure injection of glutamate onto the apical dendrites of hippocampal CA1 pyramidal cells usually produces a fast rising, brief depolarization. However, hyperpolarizing responses with longer durations (300-500 ms) can be produced over a range of drug electrode locations. These hyperpolarizations can be reversed with intracellular injection of hyperpolarizing current. Localized application of glutamate in the stratum radiatum produces a depolarizing response in intracellularly recorded CA1 interneurons. Previous studies have shown that the dendrites of GABA-ergic basket cell interneurons extend into the stratum radiatum and are involved in mediating feedforward inhibition of pyramidal neurons. The glutamate-induced hyperpolarizations observed in pyramidal neurons are probably due to direct excitation of dendrites of interneurons, which in turn produce a synaptic inhibition in pyramidal cells. PMID- 2886961 TI - NMDA receptor antagonist D-APV depresses excitatory activity produced by normorphine in rat hippocampal slices. AB - Both pentylenetetrazole and normorphine increased CA1 pyramidal cell sensitivity to afferent stimulation and caused the appearance of synchronous afterpotentials (secondary spikes). D-2-Amino-5-phosphonovalerate (D-APV) attenuated secondary spikes induced by both drugs, but had no effect on the change in excitability of the primary population spike. These results suggest that both opiates and GABA receptor antagonists are able to unmask NMDA receptors in the in vitro rat hippocampus slice preparation. PMID- 2886963 TI - What you should know about epidural analgesia. PMID- 2886964 TI - [Effectiveness of combined therapy (systemic thrombolysis, I.V. nitroglycerin and acute beta blockade) in acute myocardial ischemia]. PMID- 2886965 TI - [Effect of Minipress and Hypothiazid therapy on plasma lipoprotein lipids]. PMID- 2886966 TI - New drugs for use in 1987--Part Two. PMID- 2886967 TI - The McGill Pain Questionnaire--German version. A study on cancer pain. AB - The McGill Pain Questionnaire, widely used in English-speaking countries, has been translated into German. The objective in translating the questionnaire was to produce a translation of the words while keeping the expression of the pain quality and intensity. The results of our present study with a German-speaking cancer pain population, concerning the choice of words and pain rating values, are comparable with those of similar English-speaking patients. The superiority of this multidimensional verbal questionnaire in analysis of pain qualities over unidimensional pain intensity scales was proved. The therapeutic effect of peridural opiate analgesia was measured in 30 patients with intractable cancer pain after they had completed the questionnaire. After 5 days of therapy, there was an average of 70% relief of the total pain experience, with best results obtained in patients with bone pain in the lumbo-sacral region. PMID- 2886968 TI - Chronic use of opioid analgesics in non-malignant pain. PMID- 2886969 TI - Incidence and characteristics of pain in a sample of medical-surgical inpatients. AB - The purposes of this study were to determine the incidence and characteristics of pain in hospitalized patients and to explore the type and perceived effectiveness of pharmacologic and nonpharmacologic therapies. Three hundred and fifty-three randomly selected patients reported experiencing pain during this hospitalization; 58% of these patients experienced excruciating pain. Fewer than half of the patients with pain had a member of the health care team ask them about their pain or note the pain in the patient record. The methods perceived as most effective in decreasing pain were analgesics, sleep, immobilization and distraction. As in earlier studies, the dose of analgesic administered over a 24 h period was less than a quarter of the amount ordered. This study concluded that (1) pain in hospitalized patients is more prevalent than has previously been reported, (2) patients with pain continue to receive inadequate dosages of analgesics, and (3) the identification and treatment of patients with pain remains a significant health care problem. PMID- 2886970 TI - Features of amino acid metabolism in Moniliformis moniliformis (Acanthocephala) in vitro. AB - Experiments to investigate the metabolism of glycine, L-glutamic acid and L aspartic acid by Moniliformis moniliformis were carried out by incubating adult worms aerobically for 3 h at 37 degrees C in Tyrode's solution containing either [U-14C]glycine, L-[U-14C]glutamic acid, L-[U-14C]aspartic acid or L-[4 14C]aspartic acid. Much of the glycine and glutamic acid was absorbed by the worms, but little of either was metabolized. Aspartic acid was readily taken up and metabolized. After incubating with L[U-14C]aspartic acid, most radioactivity was found in ethanol and a volatile compound, presumed to be carbon dioxide, with smaller amounts in lactate, alanine, acetate, malate, glucose and succinate. After incubating with L-[4-14C]aspartic acid, most radioactivity was found in lactate and the presumed CO2 with small amounts in alanine, malate and succinate. No radioactivity was found associated with ethanol or acetate. Possible metabolic pathways and suggestions for a relationship between the metabolism of aspartate with that of alanine and serine in this parasite are discussed. PMID- 2886971 TI - Cryptorchidism: isolated and associated with other genitourinary defects. AB - Cryptorchidism is the most common disorder of sexual differentiation in male children, with an incidence of 3.4 per cent in the term newborn, decreasing to 0.8 per cent at 1 year of age. The mechanisms of normal testicular descent are multifactorial and include an intact hypothalamic-pituitary-testicular axis, as well as a normal gubernaculum and epididymis. In boys with cryptorchidism, the testes demonstrate degenerative changes histologically as early as 1 to 2 years of age. Both testes may be affected, even with a unilateral undescended testis. The most important long-term complications of cryptorchidism include infertility and testicular cancer. The risk of malignancy is approximately 40 times higher in male subjects with cryptorchidism than in normal men, and is highest in male subjects who have had an intra-abdominal testis and in certain intersex conditions. Orchiopexy does not appear to lessen this risk. Hormonal therapy with HCG or LH-RH has remained unproven in clinical trials in the United States; therefore, orchiopexy remains standard treatment. HCG is recommended if the clinician suspects that a testis is retractile, however. Orchiopexy should be performed between 12 and 18 months of age to prevent the degenerative changes that are demonstrable by 2 years. PMID- 2886972 TI - Misuse of syrup of ipecac. PMID- 2886973 TI - [Congenital abnormalities of the peritoneo-vaginal process]. AB - The different clinical manifestations resulting from abnormalities of the development of the peritoneovaginal process are reviewed: inguinal hernias, abnormal testicular descent, herniated ovary, hydrocele of the tunica vaginalis, hydrocele of the spermatic cord. The pathogenesis is studied on the basis of the embryology of the vaginal processus. The surgical aspects are discussed. PMID- 2886974 TI - Reflex inhibition of efferent renal sympathetic nerve activity by 5 hydroxytryptamine and nicotine is elicited by different epicardial receptors. AB - Intrapericardial administration of 5-hydroxytryptamine (5-HT) induced reflex effects consisting in an inhibition of renal sympathetic nerve activity (RSNA), bradycardia and a fall in blood pressure. Nicotine caused the same reflex effects as 5-HT. The reflex effects of both 5-HT and nicotine were abolished by vagotomy. MDL 72222, an antagonist at 5-HT M-receptors, abolished or attenuated the decreases in RSNA, heart rate and blood pressure induced by 5-HT, leaving the reflex effects of nicotine unchanged. In the absence of MDL 72222 the reflex bradycardia partially concealed a positive chronotropic response to 5-HT. After blockade of the bradycardia response by MDL 72222, 5-HT elicited a significant tachycardia, which was not altered by propranolol and phentolamine, but was prevented by phenoxybenzamine. 5-HT probably reaches the sinoatrial node and activates 5-HT receptors that mediate directly the increase in heart rate. The nicotine receptor antagonist hexamethonium selectively abolished or attenuated the reflex effects of nicotine without interfering with those of 5-HT. We conclude that 5-HT and nicotine elicit similar reflex effects in epicardial vagal nerve endings by stimulation of M-receptors or nicotine receptors, respectively. PMID- 2886976 TI - Human histone 3 F2 detects RFLPs in inbred mice, cosegregates with H4F2 and does not map to possible syntenic groups on mouse distal chromosomes 1 and distal chromosomes 3. PMID- 2886975 TI - Identification of the promoter sequences involved in the cell specific expression of the rat somatostatin gene. AB - DNA sequences containing the 5' flanking region of the rat somatostatin gene were linked to the coding sequence of the bacterial chloramphenicol acetyl transferase gene. This recombinant plasmid is active in expressing CAT activity in the neuronally derived, somatostatin producing CA-77 cell line. Deletion analyses of the somatostatin promoter show that the sequences proximal to position -60, relative to the cap site are required for expression of this promoter. A 4 base pair deletion of residues -46 through -43 within the somatostatin promoter results in a down mutation in vivo suggesting the existence of an element critical for the expression of the promoter in CA-77 cells. In addition, the somatostatin recombinant and its 5' deletion constructs preferentially express CAT activity in CA-77 cells, whereas only basal level of expression is observed in HeLa, BSC40, and RIN-5F cell lines, pointing to the cell specific nature of this promoter. PMID- 2886977 TI - Msp-1 polymorphism detected with a cDNA probe for the P-450 I family on chromosome 15. PMID- 2886978 TI - A human anonymous low copy number clone, 4c11 (D6S4), localized to 6p12-6p21, detects 2 RFLPs, one of which is moderately polymorphic. PMID- 2886979 TI - A PstI RFLP detected by probe cpX73 (DXS159) in Xq11-q12. PMID- 2886980 TI - Sst I RFLP linked to the human ets-1 gene. PMID- 2886981 TI - Two RFLPs for the human dihydrofolate reductase gene (DHFR). PMID- 2886982 TI - RFLP detected by the anonymous DNA segment E88 (D2S17) assigned to chromosome 2. PMID- 2886983 TI - RsaI RFLP in the human von Willebrand factor gene. PMID- 2886985 TI - Analgesics and pain. Current concepts. AB - The availability of a wide spectrum of analgesics (both opioid and nonopioid) to control pain, and the science evolving around their use, increases the potential for well-controlled pain. Nurses must learn this science in order to better serve their patients. PMID- 2886984 TI - Advances in control of cancer pain. AB - The wide variety of techniques and rapidly developing complex technologies currently available for managing pain, as well as the multidimensional nature of cancer pain, require that a multidisciplinary approach to treatment be used in virtually all health care settings. Members of each health care discipline have unique and very important contributions to make to the care of patients with cancer pain. This critical fact has only recently been recognized and incorporated into the management of persons with pain in inpatient, outpatient, and home settings. The development and refinement of multidisciplinary teams, coupled with the use of the most current and effective therapeutic interventions available, should result in better care of and quality of life for patients with cancer pain. PMID- 2886986 TI - Evaluation of some commercial media for the cultivation and enumeration of Clostridium perfringens from the chick intestine. AB - Four commercial media marketed for the detection and enumeration of Clostridium perfringens were found to adequately support the growth of a pure culture (ATCC 13124) of this species but enumeration of colony-forming units was difficult on Clostrisel and lecithin-lactose-agar base (LLA) media. Colonies of C. perfringens on LLA had typical opalescent zones, a distinctive feature that can aid in presumptive identification. Colonies on sulfite-polymyxin-sulfadiazone and tryptose-sulfite-neomycin (TSN) agar media were morphologically similar but black colonies were observed on TSN incubated at 46 C. Extreme difficulty was encountered in enumerating enteric bacteria from the chick intestine on Clostrisel medium because of the pinpoint size of the colonies and on LLA because of the opacity of the medium. Morphological characteristics of bacteria picked from colonies which formed after these media had been inoculated with chick intestinal contents were in sharp contrast to those of the pure culture of C. perfringens. Numbers of colony-forming units were higher than documented levels of C. perfringens in the intestine of chicks. These observations led to the conclusion that these formulations are inadequate for the selective cultivation and enumeration of this bacterial species from the intestine of healthy chicks, unless used in combination with further tests for specific identification. PMID- 2886987 TI - Allyl alcohol liver injury: suppression by ethanol and relation to transient glutathione depletion. AB - Rats metabolized a sublethal gastric dose (0.73 mmol/kg) of allyl alcohol (AIOH) within 10-15 min. Oxidation of AIOH to acrolein was accompanied by an equally rapid, but only transient depletion of hepatic reduced glutathione (GSH). GSH was restored to levels above normal within 5 hrs. Simultaneously, AIOH provoked marked elevation of alanine aminotransferase, gamma-glutamyl transpeptidase, and glutamate dehydrogenase activities in plasma and formation of lesions mainly in the periportal regions of the liver. Inhibition of alcohol dehydrogenase by 4 methyl pyrazole completely counteracted these effects. On the other hand, attempts to potentiate the toxicity of acrolein by the aldehyde dehydrogenase inhibitor cyanamide enhanced only the release of alanine aminotransferase. Co administration of ethanol (3 g/kg) inhibited the rate of AIOH oxidation by more than 90%. Although with ethanol GSH remained depleted for several hours, the release of enzymes was markedly suppressed and the histologic changes completely prevented. These results indicate that the rapid rate of acrolein formation, rather than persistently lowered GSH content, is crucial in the hepatotoxicity of AIOH. They also suggest, that oxidation of acrolein via aldehyde dehydrogenase does not represent a major pathway for its detoxication in vivo. PMID- 2886988 TI - Effects of chronic neuroleptic treatment on agonist affinity states of the dopamine-D2 receptor in the rat brain. AB - The effects of repeated oral administration to rats of three antipsychotic compounds (haloperidol 1 mumol/kg, raclopride 5 mumol/kg and remoxipride 10 mumol/kg) on agonist affinity states of the dopamine-D2 receptor were studied using 3H-spiperone binding to rat striatal homogenates in vitro. The competition between 3H-spiperone and dopamine was analyzed using the iterative nonlinear computer program LIGAND. The treatment of rats with haloperidol, raclopride and remoxipride caused an increased number of striatal dopamine-D2 receptors. In parallel to this increase in Bmax (approximately 50%) there was an increased fraction of the number of receptors being in the D2 (high) affinity state. The affinity of dopamine for the D2 (high) state was not affected while a significant decrease in affinity of dopamine for the D2 (low) state was found. The results are discussed in view of the mechanism of action of the three compounds and of neuroleptics in general. PMID- 2886990 TI - XXXIII Nordic meeting of pharmacology. Kuopio, Finland, June, 2-5, 1987. Abstracts. PMID- 2886989 TI - Effects of the dopamine D2 selective receptor antagonist remoxipride on dopamine turnover in the rat brain after acute and repeated administration. AB - The effects of the dopamine D2 selective receptor antagonist, remoxipride, on dopamine turnover in the rat brain were studied after acute and repeated administration and compared with the effects of haloperidol. Acute administration of remoxipride produced a dose-dependent increase of the concentrations of DOPAC and HVA in both striatum and olfactory tubercle + nucleus accumbens. The maximal effect of both acute remoxipride and haloperidol on dopamine turnover was attained approximately 2 hours after a single intraperitoneal administration, whereas a biphasic response was seen after oral remoxipride. Tolerance to the effects of repeated haloperidol (20 mumol/kg orally) treatment on dopamine turnover was observed as soon as after 3 days, whereas no such tolerance could be found during the first 15 days of repeated treatment with remoxipride (20 mumol/kg orally). A dose-related tolerance to the effects of remoxipride was, however, seen at higher dosages (40, 150 and 600 mumol/kg orally) and after a longer period (6 months) of treatment. PMID- 2886991 TI - Adenine nucleotide binding sites on beef heart F1 ATPase: photoaffinity labeling of beta-subunit Tyr-368 at a noncatalytic site and beta Tyr-345 at a catalytic site. AB - 2-Azidoadenine [32P]nucleotide was bound specifically at catalytic or noncatalytic nucleotide binding sites on beef heart mitochondrial F1 ATPase. In both cases, photolysis resulted in nearly exclusive labeling of the beta subunit. The modified enzyme was digested with trypsin, and labeled peptides were purified by reversed-phase high-pressure liquid chromatography. Amino acid sequence analysis of the major 32P-labeled tryptic fragments showed beta-subunit Tyr-368 to be present at noncatalytic sites and beta Tyr-345 to be present at catalytic sites. From the relationship between the degree of inhibition and extent of modification, it is estimated that one-third of the catalytic sites or two-thirds of the noncatalytic sites must be modified to give near-complete inhibition of catalytic activity. PMID- 2886992 TI - Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. AB - Recent studies have focused on the potential role of transforming growth factor type beta (TGF-beta) as an immunoregulatory peptide. In this context, we demonstrate that TGF-beta is a potent chemoattractant for human peripheral blood monocytes. At concentrations from 0.1 to 10 pg/ml, TGF-beta induces directed monocyte migration in vitro. Consistent with this observation is the expression of high-affinity TGF-beta receptors on the monocytes with a Kd of 1-10 pM. At higher concentrations of TGF-beta (greater than or equal to 1 ng/ml), monocytes are stimulated to generate biologically active mediator(s) that enhance fibroblast growth. Gene expression for one of these growth factors, interleukin 1, is induced in monocytes within hours after exposure to TGF-beta. Thus, TGF beta may provide an important signal for monocyte recruitment and for regulation of their synthesis of mediators of fibroblast growth and activity in wound healing. PMID- 2886993 TI - The PapG protein is the alpha-D-galactopyranosyl-(1----4)-beta-D-galactopyranose binding adhesin of uropathogenic Escherichia coli. AB - Uropathogenic Escherichia coli adhere to uroepithelial cells by their digalactoside alpha-D-galactopyranosyl-(1----4)-beta-D-galactopyranose [alpha-D Galp-(1----4)-beta-D-Galp or Gal alpha (1----4)Gal]-binding pili, which are composed of repeating identical subunits. The major subunit (PapA) of these pili is not required for binding, but the papF and papG gene products are essential for adhesion. Transcomplementation analysis between the pap gene cluster and a related gene cluster encoding a different binding specificity showed that PapG and not PapF is the Gal alpha (1----4)Gal-specific adhesin. Antibodies against PapG were obtained upon immunizing with whole Pap pili, showing that the adhesin is a pilus component. Antisera specific for different Pap proteins were used to demonstrate that a pilin protein, either PapA or PapE, together with both PapG and PapF, must be exposed on the cell surface to allow E. coli to bind. The DNA sequence of the papG gene is presented, and the deduced primary structure showed similarities both to the B-chain sequence of the digalactoside-binding Shigella toxin and to established amino acid sequences of pilins. PMID- 2886994 TI - Ca2+ modulators as antidotes to imipramine and neurotransmitter toxicity. AB - Flunarizine and nimodipine, Ca2+ modulators which exert antagonist effects against catecholamines and serotonin and have specific action on the brain, were used as antidotes to imipramine toxicity in the rat. Imipramine, a tricyclic antidepressant, inhibits synaptic reuptake of catecholamines and serotonin. Flunarizine administered concurrently with imipramine increased survival time significantly (p less than 0.04). After a lethal dose of imipramine (85 mg/kg) 5 out of 5 animals treated with flunarizine (2.37 +/- 1.21 mg/kg in divided doses) and 4 out of 5 animals treated with nimodipine (0.36 +/- 0.11 mg/kg) survived. The acute toxicity of imipramine might be related, in part, to drug-induced alteration in turnover of excitatory neurotransmitters which will induce intracellular Ca2+ accumulation and damage to vital organs. These toxic effects of endogenously produced neuroamines may be antagonized by nimodipine or flunarizine. PMID- 2886995 TI - Blood acetaldehyde and ethanol levels in alcoholism. PMID- 2886996 TI - MDMA as a discriminative stimulus: isomeric comparisons. AB - Using a two-lever, food-motivated discrimination procedure, eight male rats were trained to discriminate 1.5 mg/kg of racemic 3,4-methylenedioxymethamphetamine (MDMA) from its vehicle, distilled water. Once trained, the rats demonstrated a dose-related decrease in discriminative performance after administration of lower doses of MDMA (ED50 = 0.27 mg/kg). Racemic MDMA-stimulus generalization occurred with both isomers of MDMA with the ED50 of the (+) isomer calculated as 0.50 mg/kg and for the (-) isomer being 1.07. Time-course data indicate that racemic MDMA has a peak effect from 20-60 min post-injection with a declining effect from 120-240 min. This time-course closely resembles that observed by subjective reports in human abusers and, together with previous data, would indicate that the discriminative paradigm would be useful in investigations as to the neurochemical effects of MDMA. PMID- 2886997 TI - Differential effects of a new dibenzo-epine neuroleptic compared with haloperidol. Results of an open and crossover study. AB - Fluperlapine (NB-106-689) was tested on 26 schizophrenic patients in an open and crossover study. In addition to its good antipsychotic effect, it also alleviated the apathic and depressive syndromes. Six patients who had shown only slight or no improvement after 4 weeks of haloperidol therapy responded positively to fluperlapine. The alleviation of the anergic syndrome was especially impressive. The therapeutic response of the depressive-apathic syndromes could represent an important extension of pharmacotherapy for schizophrenia. The virtual lack of extrapyramidal motor side effects with fluperlapine supports an intensification of the search for other nonclassic dibenzo-epine neuroleptics. PMID- 2886998 TI - [Drug therapy of angiolopathies]. AB - The treatment of angiolopathies is rather difficult, at this time, at least concerning functional angiopathies. It is a fact that protection against cold represents, in all angilopathies, one of the main elements of the treatment besides medications which are essentially vasoactive drugs, myorelaxants or alpha blockers, and possibly venous tonics. Fluorescein or Sodium fluoresceinate at 5%, administered in slow intra-venous injections, represents one of the best treatment of acrocyanosis, in combination with vitamins A and D, given at the beginning of fall. Other angiolopathies, especially those of organic nature, are represented by allergic vascularitis and will be treated accordingly. In infectious and toxic forms, antibiotics should be prescribed in addition to steroids, preferred in allergic forms, especially granulomatous forms. In conclusion, the treatment of angiolopathies is extremely difficult, and must be particularly adapted to the clinical forms. PMID- 2886999 TI - [Algodystrophy of the upper extremity]. AB - Algodystrophy is a pathological syndrome of the limbs caused by a disturbance of the neurovegetative system of which the main consequence is a disorder of the regulation of the regional micro-circulation: pain, functional loss of use of a limb segment and the secondary appearance of trophic disorders with joint stiffening are the main symptoms of this disease. Among the etiologies, traumatic causes are first considered without forgetting nervous, visceral and drug induced causes. The treatment is based on pain killers, vascular medications, beta blockers and Calcitonin. In addition to active physical therapy, recent experiments permit to confirm the advantages of scottish baths. PMID- 2887000 TI - [Insulin receptors of the lateral hypothalamus and the effects of bilateral vagotomy on their response to adequate stimulation]. PMID- 2887002 TI - [Negative vs. positive therapy expectations and compliance vs. noncompliance]. AB - The problem of compliance is compared against that of noncompliance, these two phenomena being fundamentally different from each other and depending also on different factors. A cross-sectional investigation of schizophrenic patients showed that compliant patients do not differ from the noncompliant ones with regard to the number of subjectively experienced negative drug effects but with regard to the number of subjectively experienced positive drug effects. These findings are interpreted in such a manner that patients are less likely to be prevented from complying with a treatment by the negative effects of that treatment and are more likely to cooperate because of positive therapy expectations. The question as to what represents positive therapy experiences, is discussed, as well as the problem of promoting an understanding between the physician and the patient in respect of this important aspect of therapy. PMID- 2887001 TI - [Dynamics of the serum pipothiazine level in patients with schizophrenia during long-term treatment with this neuroleptic agent]. PMID- 2887003 TI - Endocrine responses to tryptophan infusion in schizophrenic patients treated with neuroleptics. AB - The growth hormone (GH) and prolactin (PRL) responses to intravenous L-tryptophan (LTP) were measured in 20 schizophrenics receiving long-term treatment with neuroleptics and 20 unmedicated control subjects. In the patients, the PRL response was significantly enhanced, and it correlated with PRL baseline concentration. In contrast, the patients' GH response was markedly reduced. These opposite changes in PRL and GH responses to LTP are unlikely to be accounted for by the effect of neuroleptics on serotonin receptors, but they may have been due to the blockade of DA receptors, which is known to disinhibit PRL release and to suppress that of GH. PMID- 2887004 TI - [Gamma-glutamyltransferase and alcohol consumption in primary gout]. AB - The behaviour of gamma-GT, an enzyme whose activity is related with alcohol intake, was studied in three groups of patients with primary gout, divided on the basis of alcohol intake. Poor drinkers (A) and good drinkers (B) do not show significant differences in the serum levels of gamma-GT, uric acid and triglycerides. The above parameters are highest in the group of strong drinkers (C), in which the increase in serum gamma-GT activity is statistically significant and reaches values above the normal range. PMID- 2887005 TI - [Chromosome aberrations in hematopoietic stem cells in late periods after prolonged external irradiation]. AB - At remote times following long-term external irradiation of Wistar rats with a cumulative dose of 10 Gy a 2-4-fold increase was registered in the spontaneous yield of chromosome aberrations in a population of original haemopoietic cells precursors mainly due to symmetrical inter- and intrachromosomal exchanges. PMID- 2887006 TI - Massive acroosteolysis in adult T-cell leukemia/lymphoma. AB - Adult T-cell leukemia/lymphoma is a relatively uncommon disease, most often found in Japan, the Caribbean, the southeastern United States, and South America. To date there have been few reports of its skeletal manifestations. A case is reported in a 44-year-old man in which a short history of swelling of the hands and feet and painful motion in the fingers was followed by the rapid development of severe acroosteolysis. PMID- 2887007 TI - Neuropeptides and neurotransmitters involved in regulation of corticotropin releasing factor-containing neurons in the rat. PMID- 2887008 TI - Imaging of neuropeptide-neurotransmitter interactions. PMID- 2887009 TI - [Intracellular delivery and assembly of F1-ATPase into mitochondria]. PMID- 2887010 TI - [Genetic factors involved in carcinogenesis]. PMID- 2887011 TI - [Somatostatin: physiologic significance and therapeutic applications]. PMID- 2887012 TI - [Physiologic effects of somatostatin in various organs and tissues. Mechanisms of action]. PMID- 2887013 TI - [Reflex pressure response to the electric stimulation of different parts of the rat stomach]. AB - The role of the autonomic nervous system in the pressor response to the electrical stimulation of different gastric zones has been studied in rats. The stimulus was applied before and after the following interventions: bilateral vagotomy, ganglionic blockade, alpha-adrenergic receptor blockade and beta adrenergic receptor blockade. After the ganglionic blockade no pressor responses to the electrical stimulus were observed. After the alpha-adrenergic blockade a lower pressor response was observed. A hypertensive response can be induced by mechanical, chemical or electrical stimulation of gastric receptors. It is concluded that the pressor reflex following the application of an electrical stimulus on different zones of the digestive tract is mediated by the sympathetic nervous system and that the efferent pathways are mainly alpha-adrenergic ones. PMID- 2887014 TI - Maturation of luteinizing hormone-releasing hormone (LHRH) and somatostatin (SRIF) neuronal systems in the hypothalamus of growing ewe lambs. AB - Using the immunoperoxidase method, neurons containing luteinizing hormone releasing hormone (LHRH) and somatostatin (SRIF) were identified in the hypothalamus of growing ewe lambs between 3 days and 16 weeks of age. Both peptidergic neuronal systems were well developed in the early postnatal period. The centres producing LHRH were found to be situated in the anterior region of the hypothalamus and preoptic area. Immunoreactive (ir) LHRH perikarya in growing lambs were readily stained by the various anti-LHRH antibodies used and they were generally more numerous in young animals than in foetuses and adults. The concentration of irLHRH material stored in the median eminence (ME) increased with lamb age, reaching a maximum around 12 weeks of age. The centre producing somatostatin, situated in the anterior periventricular area of the hypothalamus, did not develop before the postpartum period. The irSRIF material in the ME was greatly depleted during the first neonatal days but regained its former level by 8 weeks of age. From 10 to 16 weeks of age, these stores in the ME were again depleted. The results show that the two neuronal systems investigated developed in a different way in the growing lamb. The secretory activity of these systems changed during subsequent periods of growth. The importance of these events in the processes of body growth and reproductive system maturation are still to be determined. PMID- 2887015 TI - Isolation and purification of a Thy-1-like glycoprotein from sheep brain and its distribution in ovine tissues. AB - Standard methods for the purification of Thy-1 were applied to sheep brain to purify a sheep brain membrane glycoprotein (SBMG). On 12 per cent sodium dodecylsulphate polyacrylamide gels this glycoprotein was shown to be a doublet with apparent molecular weights 24,000 and 25,000. By a number of physicochemical criteria SBMG was shown to have properties similar to those previously reported for Thy-1 isolated from other species. Immunological investigations, however, revealed that SBMG did not react with rabbit anti-rat Thy-1 and rabbit anti-SBMG did not recognise rat or chicken brain. By fluorescent antibody techniques the tissue distribution of SBMG appeared to be similar to that of Thy-1 in other species. A small population of peripheral blood and intestinal lymph lymphocytes were stained with anti-SBMG. These results suggest that sheep have an immunologically distinct Thy-1 homologue. PMID- 2887016 TI - Autoradiographic localisation of alpha 2 adrenoceptor binding sites in the spinal cord of the sheep. AB - Alpha 2 adrenoceptor agonists, such as xylazine and detomidine, are used as sedatives, analgesics and premedicants. In this study the localisation of binding sites for alpha 2 agonist drugs in the sheep spinal cord was examined using [3H] clonidine as a ligand and autoradiographic techniques related to our initial histological mapping of the various tracts and laminae. The results indicated a high concentration of binding sites for alpha 2 adrenoceptor agonists in the lamina II region of the dorsal horn of the spinal cord (the substantia gelatinosa) which is an area widely implicated in the transmission of painful stimuli. Possibly therefore some of the analgesic effect of this group of drugs in sheep is mediated at the spinal level. PMID- 2887017 TI - Characterisation of Escherichia coli strains associated with canine urinary tract infections. AB - Of 33 Escherichia coli strains isolated from canine urinary tract infections, 22 were haemolytic and 27 were classified into O serogroups, the most common being O4, O6, O2 and O83. P-fimbriated strains were haemolytic and belonged mainly to serogroups O4 and O6. Twenty-nine strains possessed type-1 fimbriae but only small numbers possessed S fimbriae, type-1C fimbriae, X adhesins or the aerobactin system. It is postulated that P fimbriae and haemolysin production contribute to bacterial virulence in canine pyelonephritis and cystitis. PMID- 2887018 TI - Development of an enzyme-linked immunosorbent assay for the detection of phenothiazine tranquillisers in horses. AB - An acepromazine (ACP) hapten was synthesised, coupled to bovine serum albumin and injected into a horse to produce antibodies to the drug. A competitive ELISA was developed whereby ACP attached to the solid phase via lysozyme competed with free ACP present in phosphate buffered saline, horse serum or horse urine for limiting amounts of antibody. The assay could detect the presence of ACP and, or, some of its metabolites in horse urine for at least 25 hours after intravenous injection of 0.1 mg kg-1 ACP maleate, but because of non-specific interference, horse serum could not be used. As little as 0.24 micrograms ml-1 ACP or its metabolites could be detected. The level of detection and the ease of performance of the assay make it an attractive alternative to the more complex methods currently available for the screening of horse urine samples at horse races, shows and sales. PMID- 2887019 TI - Applications of basic chromosome research in biotechnology and medicine. PMID- 2887020 TI - [Are respiratory stimulants necessary? Yes]. PMID- 2887021 TI - [Are respiratory stimulants necessary? No]. PMID- 2887022 TI - [A case of polyarteritis nodosa with diffuse pulmonary hemorrhage and acute renal failure]. PMID- 2887023 TI - Meta-analysis of clinical trials as a scientific discipline. I: Control of bias and comparison with large co-operative trials. AB - Meta-analysis is an important method of bridging the gap between undersized randomized control trials and the treatment of patients. However, as in any retrospective study, the opportunities for bias to distort the results are widespread. Attempts must be made to introduce the controls found in prospective studies by blinding the selection of papers and extraction of data and making blinded duplicate determinations. Informal and personalized methods of obtaining data are probably more liable to error and bias than employing only published data. Publication bias is a serious problem requiring further research. There also need to be more comparisons of meta-analysed small studies with large co operative trials. PMID- 2887024 TI - Pharmacologic probes to identify patients with renovascular hypertension. AB - The renin-angiotensin system has been shown to play a significant role in maintaining blood pressure and sodium balance in health and disease states. The development of various pharmacologic probes that inhibit the RAS at different and specific points in the renin-angiotensin cascade has facilitated the elucidation of the role of angiotensin II in renovascular hypertension. In a clinical regard, inhibitors of the RAS have been instrumental in screening patients for renovascular hypertension, and in predicting curability with a high degree of reliability. Moreover, use of these drugs in an out-patient setting has been determined to be safe, practical, and reliable, making the work-up for renin dependent hypertension cost effective and accurate. PMID- 2887025 TI - [Unstable angina: recent findings and therapeutic applications]. PMID- 2887026 TI - Presynaptic alpha-autoreceptors. PMID- 2887027 TI - [HTLV-I infection and blood transfusion]. PMID- 2887028 TI - Effects of H1 antihistamines on canine nasal vascular and airway resistances. AB - The effects of three commonly used H1 antihistamines on the nasal vascular and airway resistances were studied in the dog. Promethazine hydrochloride decreased nasal vascular resistance but increased nasal airway resistance in a dose dependent manner. Diphenylpyraline hydrochloride in low doses increased nasal vascular resistance without affecting much nasal airway resistance while in high doses decreased nasal vascular resistance but increased nasal airway resistance. Chlorpheniramine maleate in low doses increased nasal vascular resistance but decreased nasal airway resistance while in high doses decreased nasal vascular resistance without affecting much nasal airway resistance. It was concluded that different H1 antihistamines might exert vasoconstrictor or vasodilatatory action on both the resistance and capacitance vessels of the nasal vascular bed depending on the type and the dose of the drug used. PMID- 2887029 TI - Dietary and metabolic manipulations of the carcinogenic process: role of nucleotide pool imbalances in carcinogenesis. AB - Perturbations in DNA and/or membranes are considered to be important for the carcinogenic process. A search for nutritional and metabolic means of disturbing the homeostasis of DNA and membranes revealed that nucleotide pools offer an exciting possibility. An imbalance in nucleotide pools can exert a two-pronged attack on both DNA and membranes. When given to rats, orotic acid, a precursor of pyrimidine nucleotides, results in an imbalance in nucleotide pools (an increase in uridine nucleotides and a decrease in inosine/adenine nucleotides), alterations in both DNA and membranes, and promotion of carcinogenesis in the liver initiated by chemical carcinogens. Agents such as adenine and allopurinol, which inhibit the metabolism of orotic acid and thereby decrease the formation of uridine nucleotides, and galactosamine, which traps uridine nucleotides, inhibited the promotional effects of orotic acid in the liver. These results suggested that orotic acid needs to be metabolized to uridine nucleotides and the creation of a subsequent imbalance in nucleotide pools is important for the promotional effects of orotic acid. To determine whether the creation of a nucleotide pool imbalance is a more general mechanism of tumor promotion, two lines of approach were investigated. One was to determine the effect of orotic acid on promotion of carcinogenesis in other organs, and the second approach was to determine how to induce nucleotide pool imbalances by means other than orotic acid administration. It is interesting to note that orotic acid promotes carcinogenesis in duodenum initiated by azoxymethane. Regarding the second approach, it became apparent that several metabolic disturbances result in increased orotic acid synthesis and alterations in nucleotide pools.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887030 TI - Complementarity between two rat liver tumor promoters. AB - A delay in the exposure of initiated rats to orotic acid (OA) beyond a specific time frame results in a progressive loss of promotional effect in liver carcinogenesis. The current study was designed to ascertain whether the loss of promotional effect could be counteracted by pre-exposing the initiated animals to other rat liver promoting regimens such as a diet deficient in choline (CD). Male Fischer 344 rats (150 g) were initiated with diethylnitrosamine (200 mg/kg, ip); 1 week later they were given either a CD diet or a CD diet supplemented with choline for 5 weeks. Animals from these two groups were then fed either a 1% OA diet or the basal diet for another 20 weeks. The results indicated that the loss of OAs promotion efficacy from delaying the start of the promoting regimen can be counteracted by pre-exposing the initiated rats to a CD diet. Thus in rats exposed to OA from the first week of initiation, 7% of the liver developed as nodular areas, whereas only 0.8% of liver was nodular when OA feeding was delayed by 5 weeks. This loss was abolished when initiated rats were fed a CD diet for 5 weeks prior to feeding OA for 20 weeks. These results suggest that in a rat liver tumor promotion model, two tumor promoters, OA and CD, show some degree of complementarity when given sequentially. PMID- 2887031 TI - Developments in the treatment of peptic ulcer. AB - A review is given of developments in the treatment of peptic ulcers from the early nineteenth century to modern times. 150 years ago long-term treatment consisted of antacids and dietary advice, while bed rest and starvation were included in most regimes around 1900. At the beginning of the 20th century the "Sippy regime" was adopted world wide, entailings, physical rest and complete neutralization of acid. The urge for complete elimination of acid led to the use of the continuous gastric drip. The side effects of these therapeutic modalities were considerable, and thus they were gradually abandoned, so that around 1950 only antacids and bed rest in the initial phase were recommended. During the last 20 years there have been dramatic developments in the medical treatment of peptic ulcers. The impact of the new drugs is discussed. PMID- 2887032 TI - Role of antigen-presenting cells in the cytotoxic T-cell response to minor histocompatibility antigens (MIHA). I. In vitro function of cells pulsed with MIHA in vivo. AB - Although antigen-presenting cells (APC) appear to be able to process minor histocompatibility antigens (MIHA) expressed on allogeneic cells and present them in association with intrinsic H-2 of the APC in vivo, this does not occur in vitro. This could be due to fundamentally different mechanisms of antigen handling by APC in vitro, or it could represent compromised APC function. In order to distinguish these possibilities, we designed a system in which BALB/c spleen cells are transferred into an MIHA-disparate irradiated host and allowed to reside for 2-3 days; the spleen cells of the repopulated host are removed and used as stimulator cells for the CTL response of primed BALB/c responder cells to DBA/2 MIHA. These cells are referred to as in vivo-pulsed APC (IVP-APC). Donor BALB/c cells are able to pick up DBA/2 MIHA after a passage in DBA/2 hosts and efficiently present MIHA to primed CTL precursors to generate DBA/2-specific CTL. The donor cell type able to pick up and present MIHA is present in spleen but not thymus or bone marrow, is Thy-1.2 negative, Ia+, and nylon wool-adherent. Its stimulatory capacity is as efficient on a per cell basis as that of DBA/2 spleen cells. The generation of IVP-APC requires repopulation of the irradiated host, which must express MIHA foreign to the BALB/c donor cells. When we attempted to generate IVP-APC in H-2 incompatible hosts, we found that, although the IVP-APC could present H-2 antigens, they were unable to present MIHA in association with intrinsic APC H-2 antigens. Use of intra-H-2 recombinant strains as host mice indicated that compatibility of donor and host at the KI region of H-2 was essential for the generation of IVP-APC able to present apparently unprocessed MIHA to primed BALB/c responder cells. Thus, we were unable to reproduce the antigen-processing function of APC encountering antigen in situ using an adoptive transfer method of pulsing APC with MIHA in vivo. In addition, we suggest that our results may impose constraints on the formulation of models to account for the association of MIHA with H-2 antigens. PMID- 2887033 TI - Prospective study of course of illness in schizophrenia: Part III. Treatment and outcome. AB - In a prospective study of 86 schizophrenic patients (ICD 9), outcome data were obtained for 86 percent 1 year after clinic discharge. The Strauss-Carpenter outcome scale (frequency of social contacts, employment duration, symptomatology, and duration of rehospitalization) served as the outcome criterion. The Strauss Carpenter prognostic scale items served as the potential predictors of the course. The followup treatment, which took place during the catamnestic period, was compared with that of other psychiatric diagnostic groups with respect to its continuity and efficiency. The following findings emerged: When compared to patients with neuroses and alcohol dependency, the followup treatment of schizophrenic patients in a large city seems to be better ensured. This is attributed to a clearer concept of treatment for schizophrenic patients. The comparatively favorable outcome of this group of patients seems to be related to this. For the other groups, especially for neurotic disorders, effective treatment concepts have still to be developed and evaluated. Schizophrenic patients receiving continuous neuroleptic medication are rehospitalized significantly less often (28 percent) than those not in continuous treatment (55 percent). This treatment difference is most obvious for patients with multiple admissions. Differences dependent on treatment are not found in other outcome dimensions. However, patients with good heterosexual adjustment profit the most from continuous treatment with neuroleptics in reference to freedom from symptoms. For a more chronic subgroup with a poorer initial level of work adjustment, the functional level deteriorates over the course of illness. Relapse and inpatient readmission are related to retarded recompensation, particularly for chronic patients. This underlines the need for consistent neuroleptic treatment. PMID- 2887034 TI - Adrenal medulla grafts enhance recovery of striatal dopaminergic fibers. AB - The drug, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), depletes striatal dopamine levels in primates and certain rodents, including mice, and produces parkinsonian-like symptoms in humans and nonhuman primates. To investigate the consequences of grafting adrenal medullary tissue into the brain of a rodent model of Parkinson's disease, a piece of adult mouse adrenal medulla was grafted unilaterally into mouse striatum 1 week after MPTP treatment. This MPTP treatment resulted in the virtual disappearance of tyrosine hydroxylase-immunoreactive fibers and severely depleted striatal dopamine levels. At 2, 4, and 6 weeks after grafting, dense tyrosine hydroxylase-immunoreactive fibers were observed in the grafted striatum, while only sparse fibers were seen in the contralateral striatum. In all cases, tyrosine hydroxylase-immunoreactive fibers appeared to be from the host rather than from the grafts, which survived poorly. These observations suggest that, in mice, adrenal medullary grafts exert a neurotrophic action in the host brain to enhance recovery of dopaminergic neurons. This effect may be relevant to the symptomatic recovery in Parkinson's disease patients who have received adrenal medullary grafts. PMID- 2887035 TI - Homeo domain of the yeast repressor alpha 2 is a sequence-specific DNA-binding domain but is not sufficient for repression. AB - The alpha 2 protein, the product of the MAT alpha 2 gene, is a regulator of cell type in the yeast Saccharomyces cerevisiae. It represses transcription of a group of cell type-specific genes by binding to an operator located upstream of each target gene. Fifteen in-frame deletions within the coding region of the MAT alpha 2 gene were constructed. The deletion alleles were examined for phenotypes conferred in vivo, and the encoded mutant proteins were assayed for ability to bind specifically to the operator in vitro. This analysis has revealed that the sequence-specific DNA-binding domain of alpha 2 is located within a region of 68 amino acids. This region of alpha 2 has significant homology with the homeo domain, a conserved sequence found in the products of several Drosophila homeotic and segmentation genes. In addition, there is a class of mutant alpha 2 proteins that binds tightly and specifically to the operator in vitro, but fails to repress transcription in vivo. PMID- 2887036 TI - [Fluanxol]. PMID- 2887037 TI - [Management of phobic disorders]. PMID- 2887038 TI - Infantile polyarteritis nodosa with mucocutaneous lymph node syndrome treated with long-term corticosteroids. AB - Clinical and pathologic similarities between infantile polyarteritis nodosa (IPN) and mucocutaneous lymph node syndrome (MLNS, or Kawasaki disease) have suggested that these entities may be different manifestations of the same basic disease process. We have described a boy with IPN/MLNS treated with long-term corticosteroids for more than eight years after the appearance of multiple aneurysms at 11 months of age. Corticosteroid therapy may be appropriate in the treatment of selected patients with IPN/MLNS if based on age and the presence of aneurysms. PMID- 2887039 TI - [A. I. Voinova-Dandurova's "Notes of a Girl Student"]. PMID- 2887040 TI - Myocardial opiate receptor activity is stereospecific, independent of muscarinic receptor antagonism, and may play a role in depressing cardiac function. AB - Earlier work has shown that morphine sulfate can produce a dose-related decrease in heart rate (HR) and cardiac output (CO) in isolated working rat hearts. This response is preventable with the use of the opiate receptor antagonist, naloxone hydrochloride. In this study, the stereospecificity of the opiate response was tested with the use of levorphanol tartrate and its d-isomer, dextrorphan, in our Langendorff rat heart model. The interaction of muscarinic receptor activity with the opiate response was tested by first adding bethanechol chloride to the perfusate in the presence and absence of atropine (5 X 10(-9) mmol/L). Our earlier studies with morphine sulfate were then repeated in the presence of the same concentration of atropine. At a concentration of 5 X 10(-6) mmol/L, levorphanol tartrate produced a significant decrease in CO (p less than 0.05), while a similar concentration of dextrorphan produced little change in either HR or CO. Bethanechol chloride, in a concentration of 3 X 10(-6) mmol/L, produced a significant decrease in HR and CO (p less than 0.05), which was prevented by atropine. When morphine sulfate was added to the standard perfusate (3 X 10(-4) mmol/L), HR and CO were significantly decreased (p less than 0.05). This change was not prevented by the addition of atropine. The opiate effect on myocardial function is mediated by a stereospecific opiate receptor, which acts independently of muscarinic receptor antagonism. PMID- 2887041 TI - Treatment of acute pancreatitis with beta-adrenergic agonist drugs. AB - An increase in microvascular permeability may be important in the pathogenesis of acute pancreatitis. beta-adrenergic receptor agonist drugs are known to inhibit the increase in microvascular permeability induced by histamine and related vasoactive substances. These inflammatory mediators have been shown to be released during the course of experimental and human pancreatitis. We investigated the effect of isoproterenol and terbutaline sulfate on the development of acute edematous (AEP) and acute hemorrhagic (AHP) pancreatitis in a feline model of biliary pancreatitis. When given at the time of pancreatic insult, isoproterenol prevented the development of both AEP and AHP. Both isoproterenol and terbutaline sulfate reduced the severity of pancreatic inflammation, even when given up to 12 hours after the onset of AEP. Although neither drug was effective in treating established AHP, our findings suggest that, if given early in the course of the disease, they may be useful in preventing the progression of AEP to AHP. PMID- 2887042 TI - [Results from the Diakonhjemmet--nurses knowledge of and attitude towards HIV infection]. PMID- 2887043 TI - Adjuvant pain treatment in cancer: a case for psychopharmacology. PMID- 2887044 TI - [The test of serum GGT decrease after alcoholic withdrawal. Study in 221 patients treated with Atrium]. PMID- 2887045 TI - Determination of the HLA-DR profile of an HLA class II negative carcinoma cell line by restriction fragment length polymorphism (RFLP) analysis. AB - The human colonic adenocarcinoma cell line HT-29 does not normally express HLA class II molecules. By restriction fragment length polymorphism (RFLP) analysis of DNA with a DR beta-probe, we analysed the genomic DR beta polymorphism of this cell-line, and compared it with the RFLP patterns seen in DNA from a reference panel of different DR homozygous and heterozygous cells. The HT-29 cell-line expressed DR beta fragments similar to the sum of the fragments expressed by DR4 and DR7 homozygous cells. The DR4 and DR7 haplotypes of HT-29 was further confirmed by comparing the RFLP patterns of four DR4/7 heterozygotes with that of HT-29. Furthermore, the HT-29 cell line expressed a Hind III 9.3 kb fragment previously found to be strongly associated to DRw53. Following treatment with gamma-interferon, the HT-29 cells could be induced to express class II molecules. Serological typing revealed the presence of the DR4, DR7 and DRw53 antigenic determinants. PMID- 2887046 TI - Cytotoxicities of sodium benzoate in primary culture of hepatocytes from adult rat liver. AB - The cytotoxicities of sodium benzoate was studied using primary culture of hepatocytes established from adult rat liver by a collagenase perfusion technique and maintained as a monolayer in serum-free culture medium. The activities of ornithine transcarbamylase (as a marker of mitochondria) and tyrosine aminotransferase (as a marker of cytosol) were clearly suppressed by sodium benzoate at concentration in excess of 500 micrograms/ml. Intracellular protein synthesis and DNA synthesis were also suppressed, and the suppression of DNA synthesis was observed even with a lower concentration of benzoate (100 micrograms/ml). PMID- 2887047 TI - Separation of two myotoxins from nematocysts of the box jellyfish (Chironex fleckeri). AB - Two myotoxins, both lethal to mice by i.v. injection, were obtained by chromatography on Sephadex G-200 of material released from isolated microbasic mastigophores of C. fleckeri. Both toxins elicit contractures of skeletal (diaphragm) musculature of the rat and of smooth (ileum and vas deferens) and atrial musculature of the guinea-pig, although consistent differences in the parameters of the contractures of each muscle type elicited by the two toxins are shown. Moreover, one toxin, with a molecular weight of approximately 150,000, also elicits activity on crustacean (barnacle) musculature, whilst the other toxin, with a molecular weight of approximately 600,000, elicits no activity in barnacle musculature at the concentrations tested. The toxins are labile when released from nematocysts and they lose all myotoxic activity within 3 days at 5 degrees C. They can also be isolated chromatographically from crude extracts of the contents of mixed nematocysts of C. fleckeri. They are considered to be the principal toxins injected by C. fleckeri during nematocyst discharge and appear to be different from the C. fleckeri toxins described by other workers. PMID- 2887048 TI - [Prevention of the toxic action of carbon disulfide on the oral mucosa of experimental animals]. PMID- 2887049 TI - Enzyme linked protein-A: an ELISA for detection of amoebic antibody. AB - Enzyme linked protein-A was used to develop an enzyme linked immunosorbent assay (ELISA) system for the detection of circulating antibodies to amoebic antigen. The specificity of protein-A to bind IgG only through Fc receptors, makes the test more specific for the detection of IgG antibodies to amoebic antigen. The ELISA system was used to detect amoebic antibody in control subjects (56), patients with amoebic liver abscess (79) and Entamoeba histolytica cyst-passers (10) and the results compared with those of indirect haemagglutination assay (IHA). The ELISA was more sensitive and detected 74.7% of cases with amoebic antibody in amoebic liver abscess compared with 66.7% detected by IHA. The test was more specific, sensitive and easy to perform and is recommended as a test of choice for the serological diagnosis of amoebic liver abscess. PMID- 2887050 TI - Anthropophilic mosquitoes at Richards Bay, Natal, and arbovirus antibodies in human residents. AB - A survey at Richards Bay, the site of a new international harbour on the east coast of South Africa, revealed the presence of 11 anthropophilic mosquito species. These are discussed in relation to their known medical importance and to a complementary survey of arbovirus antibodies among residents of the area. Mansonia uniformis was by far the most abundant man-biting mosquito. Antibodies against Germiston, Banzi and Rift Valley Fever viruses were the three most commonly encountered, being detected in 29.7, 12.2 and 8.7% of residents respectively. This new knowledge updates the distribution and prevalence of arbovirus antibodies in man in northern Natal. PMID- 2887051 TI - The role of autoantibody to vascular endothelial cell antigens in atherosclerosis and vascular disease. PMID- 2887052 TI - Antibody-mediated causes of male infertility. AB - It is probable that antisperm antibodies identified directly on a man's sperm's surface correlate best with the presence of antibody-mediated infertility in males. Care must be taken in reviewing the literature regarding antisperm antibodies in men, since many studies are based on measurement of antibodies in the circulation or have utilized antigens (such as solubilized or fixed sperm) that are not on the sperm surface. The results of these assays that are not measuring antibodies against the sperm plasma membrane may not be clinically significant, since the sperm plasma membrane remains intact in sperm participating in in-vivo fertilization until after the acrosome reaction. Treatment of antibody-mediated infertility in the male is difficult at the present time, although newer techniques are promising. PMID- 2887053 TI - New therapy for impotence. AB - In the not too distant past, the physician caring for the impotent patient had few therapeutic options. With the recent advances in penile pharmacotherapy, vascular surgery, and prosthetics, several possibilities for treatment are now available. Before a decision is made, however, numerous factors must be taken into consideration: age, manual dexterity, cause of erectile dysfunction, psychological attitude, and social considerations. Clearly, the choice of therapy for impotence must now be made on an individual basis after a careful diagnostic evaluation and in-depth consultation with the patient. Only then can the treatment that offers the highest likelihood of success, both functional and emotional, be chosen. PMID- 2887054 TI - Canine pancreatic endocrine tumors: immunohistochemical analysis of hormone content and amyloid. AB - Thirty-one primary canine pancreatic endocrine tumors and their metastases were studied histologically and immunohistochemically for the presence of insulin, glucagon, somatostatin, pancreatic polypeptide (PP), gastrin, and adrenocorticotrophic hormone (ACTH). Tumors were also evaluated for the presence of amyloid. The cytoarchitectural pattern of 25 of 31 primary tumors was predominantly solid, whereas three tumors were mostly glandular, two were unclassified, and one had a gyriform pattern. Cells with insulin immunoreactivity were found in 30 of 31 tumors and were found in all cases in which there was clinical evidence of inappropriate insulin secretion. Insulin was the only hormone demonstrable in three of the 30 tumors, but cells immunoreactive for other hormones were also present in various combinations in most tumors [i.e., glucagon (13 of 30), somatostatin (17 of 30), PP (25 of 30), and gastrin (2 of 30)]. One tumor contained only cells with glucagon and PP immunoreactivity. Amyloid was found in ten of 31 primary tumors but was not detected in metastases. Cells with insulin immunoreactivity were the only cell type consistently present in tumors containing amyloid. Amyloid deposits did not immunoreact with any of the antisera. Seventeen of 31 dogs had metastasis of the pancreatic endocrine tumor to regional lymph nodes, liver, or both. All metastases available for study (15 of 17) contained cells with insulin immunoreactivity and some contained cells with PP or somatostatin immunoreactivity. No statistically significant (P greater than 0.05) differences in tendency to metastasize were found when pancreatic endocrine tumors were compared by region of origin, cytoarchitectural pattern, presence of amyloid, or by number of hormones contained within the tumor. PMID- 2887055 TI - Clostridium perfringens in pelleted feed. PMID- 2887056 TI - Kidney extract reversibly inhibits compensatory cell proliferation after unilateral nephrectomy. AB - Unilateral nephrectomy (uNX) in mice is followed by a transitory increase in cell proliferation in the remaining kidney. To examine whether this response could be related to a negative feedback control of kidney epithelial cell renewal, water extracts were made of kidney homogenate. Five mg freeze-dried extract was injected 18 h post-operatively, and the animals were sacrificed at intervals during the following 54 h. The mitotic rate and the incorporation of tritiated thymidine (3H-TdR) into DNA were measured in the remaining kidney. The results show that the kidney extract reduces both the mitotic rate and the incorporation of 3H-TdR into DNA. In the tubular epithelium in the kidney, the strongest inhibitory effect was found by injecting the extract at 18 or 39 h postoperatively. PMID- 2887057 TI - Ultrastructural aspects of streptozotocin cytotoxicity on rat pancreatic islets in vitro. Test of a protective effect of zinc. AB - Pancreatic islets, newly formed in vitro were incubated in the presence of streptozotocin (STZ; 0.4 mM) for up to 6 h. Ultrastructural changes first appeared between 2 and 4 h; heterochromatization, was followed by swelling of nuclear and reticular membranes, vesiculation of the Golgi apparatus, fragmentation of cell membranes and finally mitochondrial destruction. At the end of the experiment all the B cells were destroyed, whereas the other cell types remained intact. Exogenous ZnSO4 was added during preincubation periods to increase the intrainsular zinc content and to determine any protective effect against STZ-cytotoxicity. Since the addition of zinc had no obvious effect, it is suggested that STZ cytotoxicity on B cells cannot be attributed to competition for zinc between copper-zinc superoxide dismutase (Cu-Zn-SOD) and the crystallization of insulin. PMID- 2887058 TI - The establishment of two rat colonic carcinomas in tissue culture. A basic prerequisite for standardized experiments on the biology of colonic carcinomas in vivo. AB - Two rat colonic carcinomas (DMH-Co-1 and DMH-Co-2) derived from dimethyl hydrazine-induced metastasizing adenocarcinomas were established as permanent cell lines. By means of electron microscopy, immunofluorescence microscopy and biochemical analysis of cytoskeletal components, it has been shown that both tumor cell lines retain in vitro the phenotypic characteristics of the primary tumors. The in vitro growth properties revealed only minor differences between the two cell lines. After retransplantation in vivo, DMH-Co-2 gave rise to moderately differentiated adenocarcinomas, whereas the tumors arising from DMH-Co 1 exhibited a continuum of differentiation encompassing adenocarcinomas, undifferentiated carcinomas and squamous cell carcinomas. These permanent cell lines offer the opportunity for isolating divergent subpopulations by in vitro cloning and facilitate standardized experiments on their biological behaviour in vivo. PMID- 2887059 TI - Effect of tryptophan on isolated hepatocytes of rats. AB - The addition of tryptophan to adult rat hepatocyte cultures stimulated DNA synthesis. The increase in DNA synthesis as measured by 3H-thymidine incorporation into DNA was observed on treatment of the cultures with tryptophan for 48 h but also as short as for 6 h in comparison with control cultures. An increase was also apparent at 30 h which was maintained for up to 48 h post treatment with tryptophan. The increase in DNA synthesis by tryptophan cannot be attributed to cell injury or to increased DNA degradation. Of the degradative enzymes added after harvesting the hepatocytes, only DNase decreased incorporation of 3H-thymidine. The observed effect was specific for tryptophan since treatment with kynurenine, isoleucine, methionine or serine failed to show a significant effect. Pretreatment of cultured hepatocytes with hydroxyurea prevented the tryptophan stimulated increase in DNA synthesis suggesting that the latter was due to replicative and not to reparative DNA synthesis. Experiments performed with the addition of diethylnitrosamine also alluded to tryptophan's role in replicative DNA synthesis. The mechanism of tryptophan-induced DNA synthesis is discussed. PMID- 2887061 TI - Characterization of the proteolytic compartment in rat hepatocyte nodules. AB - Persistent liver nodules (hepatocyte nodules, neoplastic nodules) were produced in rat liver by intermittent feeding with 2-acetylaminofluorene. Dense bodies (secondary lysosomes) were purified and characterized from the nodules. The purity of the dense body fraction was 90%. The levels of various lysosomal enzyme activities were lower in these dense bodies in comparison with dense bodies from control liver. Similarly, protein degradation was 50% lower in dense bodies from liver nodules than in control liver. The number of autophagic vacuoles (AVs) in the nodular tissue increased considerably after 3 h vinblastine treatment. We have taken advantage of this expansion in an effort to isolate these organelles from liver nodules. Autophagic vacuoles have been isolated recently from liver and kidney but not from putatively premalignant liver nodules. Fraction purity of AVs from liver nodules was 95%. As with dense bodies, AVs from nodular tissue displayed lower activities of proteinases and lower rates of protein degradation when compared with their counterparts from normal liver tissue. Accordingly, the lower rate of overall protein degradation in liver nodules can be ascribed to a decrease in lysosomal activity. A diminished autophagic sequestration capacity is the most plausible explanation for the decreased rate of proteolysis in cells. This could conceivably give these nodular cells a growth advantage and assist in their selective outgrowth as well as in their transformation from neoplastic into true cancer cells. PMID- 2887060 TI - Thyroid and pituitary secretory disorders in streptozotocin-diabetic rats are associated with severe structural changes of these glands. AB - Streptozotocin diabetes in rats is associated with reduced function of the hypothalamo-pituitary-thyroid axis. The structure and hormone secretion of the thyroid and pituitary glands were studied in adult male rats 1 month after streptozotocin injection. The thyroid of diabetic rats was characterized by decreased follicle area and epithelial thickness. By electron microscopy, thyroid epithelial cells were characterized by flattened and almost empty rough endoplasmic reticulum cisternae, scanty exocytotic apical and endocytotic vesicles as well as degenerate mitochondria and rough endoplasmic reticulum. By immunohistochemistry, intracolloidal thyroglobulin and T3 as well as intraepithelial thyroglobulin were reduced. Electron microscopic and immunohistochemical analysis of pituitary glands showed that in diabetic rats thyrotrophs were mostly of type II, and the number of thyrotrophs (type I + type II) was greater than in controls. By radioimmunoassay (RIA), plasma T3, T4, and TSH levels were markedly reduced, and the TSH response to TRH was deficient in diabetic animals. The pituitary TSH concentration was increased, as expected from the morphological data. This study demonstrates severe structural changes in the thyroid and pituitary glands of diabetic rats which are accompanied by marked alterations of their secretory activity. PMID- 2887062 TI - Immunohistochemical, electron microscopic and morphometric studies of estrogen induced rat prolactinomas after bromocriptine treatment. AB - To clarify the effects of bromocriptine on prolactinoma cells in vivo, immunohistochemical, ultrastructural and morphometrical analyses were applied to estrogen-induced rat prolactinoma cells 1 h and 6 h after injection of bromocriptine (3 mg/kg of body weight). One h after treatment, serum prolactin levels decreased markedly. Electron microscopy disclosed many secretory granules, slightly distorted rough endoplasmic reticulum, and partially dilated Golgi cisternae in the prolactinoma cells. Morphometric analysis revealed that the volume density of secretory granules increased, while the volume density of cytoplasmic microtubules decreased. These findings suggest that lowered serum prolactin levels in the early phase of bromocriptine treatment may result from an impaired secretion of prolactin due to decreasing numbers of cytoplasmic microtubules. At 6 h after injection, serum prolactin levels were still considerably lower than in controls. The prolactinoma cells at this time were well granulated, with vesiculated rough endoplasmic reticulum and markedly dilated Golgi cisternae. Electron microscopical immunohistochemistry revealed positive reaction products noted on the secretory granules, Golgi cisternae, and endoplasmic reticulum of the untreated rat prolactinoma cells. However, only secretory granules showed the positive reaction products for prolactin 6 h after bromocriptine treatment of the adenoma cells. An increase in the volume density of secretory granules and a decrease in the volume densities of rough endoplasmic reticulum and microtubules was determined by morphometric analysis, suggesting that bromocriptine inhibits protein synthesis as well as bringing about a disturbance of the prolactin secretion. PMID- 2887063 TI - Compensatory cell proliferation in the kidney after unilateral nephrectomy in mice. AB - The compensatory cell proliferation in kidney cortex after unilateral nephrectomy in hair-less mice was evaluated by registration of the mitotic rate, thymidine incorporation into DNA, and labelling indices (LI) over a period of 120 h after surgery. Maximal specific activity of DNA and LI were found at 30-36 h postoperatively and preceded the maximal mitotic rate by 6-12 h. The influence of age, sex and diurnal variations was examined. PMID- 2887064 TI - Identification of the major cottontail rabbit papillomavirus late RNA cap site and mapping and quantitation of an E2 and minor E6 coding mRNA in papillomas and carcinomas. AB - The capsite of the 2.6- and 4.8-kb major late transcripts of cottontail rabbit papillomavirus (CRPV) has been mapped by primer extension. A leader exon of about 300 nucleotides common to both RNAs is located in the untranslated region of the genome upstream of the capsites for early transcripts. In contrast to the early capsites which are all preceded by TATA boxes, no such sequence is present 30 nucleotides upstream of the late capsite. These data indicate that the switch from early to late transcription involves recognition of a new promoter and suppression of transcription termination at the early polyadenylation site. We have also identified a minor exon with a coding potential for a putative E2 transactivating protein. Quantitation by S1 mapping of the E2 coding exon and a minor exon coding for a full-sized E6 protein unique in size to the highly oncogenic CRPV did not reveal differences in the level of transcription between papillomas and carcinomas. PMID- 2887065 TI - Resistance of a measles virus mutant to fusion inhibitory oligopeptides is not associated with mutations in the fusion peptide. AB - The nucleotide sequence and predicted amino acid sequence has been obtained for the fusion (F) protein gene of the R93 strain of measles virus and compared to that of the parental strain, Edmonston B. The R93 strain is a mutant measles virus which is able to grow and induce cell fusion in the presence of the fusion inhibiting oligopeptide, Z-D-Phe-L-Phe-L-(NO2)Arg (SV4814). Primer extension sequencing on isolated R93 mRNA demonstrated the presence of three nucleotide changes leading to three amino acid changes, none of which are in the hydrophobic NH2-terminal region of the F1 polypeptide. PMID- 2887066 TI - A human papilloma virus type 11 transcript encoding an E1--E4 protein. AB - The human papilloma virus (HPV) associated with a genital wart (condyloma acuminatum) was determined to be type 11. The majority of the viral DNA molecules were monomeric circles present in the cells at high copy number, as demonstrated by one- and two-dimensional agarose gell electrophoretic separation followed by Southern blot analysis. A cDNA library in phage lambda gt11 was constructed from poly(A)-selected mRNA recovered from the tissue. Recombinant clones corresponding to the most abundant 1.2-kb viral mRNA species detected by Northern blot hybridization and by electron microscopic analysis of R loops were isolated and their nucleotide sequence was determined. Comparison to the prototype HPV-11 DNA sequence revealed that this message consisted of two exons. The promotor-proximal exon spanned nucleotides 716 through 847 and the distal exon included nucleotides 3325 through 4390 or 4392. The mRNAs were alternatively polyadenylated after either of these latter two sites, in both cases following a G and preceding a U residue. Fourteen or sixteen bases upstream from the poly(A) was the hexanucleotide AGUAAA, which apparently serves as the signal for cleavage and polyadenylation of the nascent message. The splice donor and acceptor sites conformed to the usual /GU. . .AG/pattern. The exons joined open reading frame (ORF) E1, which contributed the initiation codon and four additional triplets, to ORF E4, which specified 85 amino acids to encode a protein of 10,022 Da. The cDNA also contained the ORFs E5a and E5b toward the 3' end. The complete sequence of the cDNA revealed three single-base changes from the prototype HPV-11, two resulting in altered amino acids in E4. Neither affects the coding potential of the overlapping E2 ORF. The function of the E1--E4 protein is unknown. PMID- 2887067 TI - [Electrocardiographic changes in patients with acute benzodiazepine poisoning]. PMID- 2887068 TI - [Hemorrhagic fever with the renal syndrome]. PMID- 2887069 TI - [Hereditary multiple endocrine neoplasm syndromes]. AB - Three syndromes of multiple endocrine neoplasia (MEN) have been identified to date: MEN--I, IIa and IIb. They involve various combinations of endocrine neoplasia and occur mostly in young patients. Predisposition transmission mechanism is autosomal-dominant with total penetration and variable expressiveness. Patients' families should undergo screening which involves identification of biochemical markers and cytogenetic examination. This would allow identification of subjects at high risk for cancer and improvement of early diagnosis. PMID- 2887070 TI - [Cell subpopulations of pyelonephritis patients studied using monoclonal antibodies]. AB - The paper is devoted to a very important problem of immune mechanisms participation in the origination and maintenance of the inflammatory processes in kidneys and urinary ducts. The results from the study of lymphocyte subpopulations, making use of monoclonal antibodies in patients with clinical laboratory data about chronic pyelonephritis without chronic renal insufficiency, as compared with healthy controls, are reported. Significantly reduced total T lymphocyte (OKT1+) were established as well as T-helpers lymphocytes (OKT4+) and increased number of monocytes (OKM5+). The values are presented as weighted geometrical mean. A likely interpretation of those data is rather difficult at the present stage. PMID- 2887071 TI - [Relaxation and rapid filling of the left ventricle in essential hypertension during treatment with a non-selective beta blocker]. AB - Some indices of relaxation and rapid filling were evaluated in the course of a six-month treatment with non-selective beta-blocker in 30 patients with hypertonic disease, (HD), degree II, with echocardiographically confirmed left ventricular hypertrophy and normal systolic function. The phase analysis of the early diastole, performed according to Alvarez and Goodwin, reveals a progressive shortening of the period of isovolumetric relaxation and lengthening of the period of active suction with no change in the summed up period of rapid relaxation; the period of rapid filing is lengthened on account of the active suction. The evaluated via computer analysis (echo-computer--NIEMT-MA, Sofia) parameters of rapid filling of M-type echogram of left ventricle (maximum velocity of increase of left-ventricular dimension, mean velocity of fraction of rapid filling) increase progressively. The dynamics of the indices of diastolic function described, reflect the diminution of the restriction of ventricular filling and its shifting to the early diastole. PMID- 2887072 TI - Clorazepate use may prevent alcohol withdrawal convulsions. AB - Clorazepate dipotassium was administered orally for the five-day prophylactic treatment of potential, incipient and overt withdrawal signs and symptoms in 226 patients on admission to an inpatient alcohol treatment unit. Conservative estimates based on these patients' histories and on literature reports predicted that between 7 and 40 (3% to 18%) of these persons would be expected to have a withdrawal convulsion. No patients experienced convulsions. This complete absence of seizures suggests that clorazepate is effective in counteracting convulsive and other manifestations of the alcohol withdrawal syndrome. PMID- 2887073 TI - [Treatment of coronary heart disease with the beta-1-receptor blocker celiprolol in a long-term study over a 12-month period]. AB - In the present study, the beta-receptor-blocker Celiprolol was tested for its antianginal effects during an observation period of 12 months; 29 patients, both male and female, with definite coronary heart diseases, were subjected to this study. In general Celiprolol was well accepted by the patients, the dosage being 200 mg every morning. Regarding intensity and frequency, the side effects were negligible. It was possible to lower the intensity and frequency of angina attacks considerably during the treatment with Celiprolol. Exercise examinations were carried out at prescribed intervals and showed an increase in pain free working capacity and a decrease in the hypoxic ST-depression on the ECG, also to a considerable extent. The indication for the use of Celiprolol in long-term treatment of coronary heart disease was impressingly confirmed. PMID- 2887074 TI - [ECG findings in therapy control in the use of beta receptor blockers in primary care]. PMID- 2887075 TI - [General practice-relevant diagnostic and differential diagnostic aspects of collagen diseases. Sclerodermia progressiva, dermatomyositis and periarteritis nodosa]. PMID- 2887076 TI - [Current therapy: immunopharmaceuticals]. AB - Immunopharmarca are classified as follows: thymus factors and hormones, lymphokines and cytokines, microbial products, drugs with potential effects on the immune system, and external immunomodulators. We discuss new drugs and substances such as Timunox, Tp-1 Serono, delimmun, Isoprenosine, recombinant interleukin 2, Immuneron, tumor necrosis factor, Sandimmun, and diphencyprone, as well as drugs already known like Levamisole, Bestatin, gold, sulfones, and sulfopyridines. PMID- 2887077 TI - Effects of serial passage of Autographa californica nuclear polyhedrosis virus in cell culture. AB - A study of the major genomic alterations occurring during serial passage of Autographa californica nuclear polyhedrosis virus (AcNPV) in a Trichoplusia ni cell line was conducted. Progeny viruses from 24 independent passages were randomly selected and analyzed with restriction endonucleases. Specific deletion mutations were generated repeatedly in the PstI-G (7.6 to 13.1%) and the PstI-I (14.4-17.9%) regions; these mutations became predominant in the serially passaged stocks in which they arose. The deletions in the PstI-G region and two different insertions in this region were mapped to a 1 Kb PvuII-Bg/II fragment (9.85 10.70%) reflecting a high degree of sequence specificity in the initiation or selection of genomic alterations in this region. Insertional mutations were observed frequently and repeatedly within the PstI-E/HindIII-I region (33.6 37.2%) of the AcNPV genome. Individual examples of insertional mutations were observed in several other regions of the genome. PMID- 2887078 TI - Raw beef, pork and chicken in Japan contaminated with Salmonella sp., Campylobacter sp., Yersinia enterocolitica, and Clostridium perfringens--a comparative study. AB - One hundred and twenty samples each of raw ground beef, pork and chicken from ten local grocery stores in Shimane Prefecture, Japan, were examined for the presence of Salmonella sp. (Sal), Campylobacter jejuni (Cj), Campylobacter coli (Cc), Yersinia enterocolitica (Ye), and Clostridium perfringens (Cp) from April 1984 to March 1985. A total of 205 isolates of Sal (112 strains), Cj (64 strains), Cc (one strain), Ye (7 strains) and Cp (21 strains) were recovered from 17 beef (14.2%), 31 pork (25.8%) and 94 chicken (78.3%) of 120 samples each. Sal biogroup 1 was found in 8.3% of beef, 13.3% of pork and 35.0% of chicken, Sal biogroup 2 in 0.8% of beef, 4.2% of pork and 14.2% of chicken, Cj in 1.7% of beef and pork and 50.0% of chicken, Cc in 0.8% of pork, Ye serotype 03 was found in 5.0% of pork, and Cp in 1.7% of beef and pork and 10.8% of chicken. These enteropathogens were recovered concomitantly from two pork and 31 chicken samples, especially Sal and Cj. Sal was counted at less than or equal to 10(2)/100 g of beef and pork and at less than or equal to 10(3)/100 g of chicken, Cj was counted at less than or equal to 10(1)/g of beef and pork and at less than or equal to 10(2)/g of chicken, Ye serotype 03 was counted at less than or equal to 10(3)/g of pork, Cp was counted at less than or equal to 10(2)/g of pork and at less than or equal to 10(2)g of chicken, and Cc from pork and Cp from beef were recovered by using enrichment culture. This investigation showed that a second-contamination of Sal and Cj from chicken to beef and pork frequently occurred during the warm months of the year. It was suggested that chicken may become a source of infection with plural organisms of enteric pathogens, especially Sal and Cj, at the same time all the year round, and that pork may be an important source of infection with Ye during the cold months. PMID- 2887080 TI - Pancreatic endocrine tumour producing growth hormone-releasing hormone associated with multiple endocrine neoplasia type I syndrome. AB - We report the first documentation of GHRH production by a tumour associated with proven multiple endocrine neoplasia (MEN). A 30-year-old woman had hypoglycaemia, hyperparathyroidism, and pituitary adenoma with hyperprolactinaemia. Serum growth hormone elevation was attributed to hypoglycaemia but plasma GHRH was elevated. Subtotal pancreatectomy revealed multiple endocrine tumours and nesidioblastosis. Immunohistochemistry demonstrated insulin, glucagon, and somatostatin in several tumours. GHRH was localized in the largest one and was released from that tumour in vitro. Post-operative plasma GH returned to normal. Excess secretion of humoural factors by one tumour may stimulate growth of other tumours in MEN syndromes. The prevalence of GHRH in MEN-I tumours remains to be established. PMID- 2887079 TI - Influence of experimental diabetes on brain levels of monoamine neurotransmitters and their precursor amino acids during tryptophan loading. AB - The variations in serum and brain concentrations of the large neutral amino acids and the simultaneous changes in brain levels of monoamine neurotransmitters have been studied in normal and streptozotocin-diabetic rats after tryptophan loading. An impaired acute accumulation of tryptophan and serotonin in the brain of diabetic rats was observed, concomitantly with a much faster disappearance of the administered tryptophan from the bloodstream in these animals than in controls. Following the tryptophan load, transient differences in the brain levels of catecholamine neurotransmitters became also apparent between the two groups of rats in correlation with differences in the brain uptake and levels of tyrosine. In diabetic animals, the basal brain concentrations of serotonin and dopamine were normal and those of norepinephrine were increased. Since uptake of the precursors tryptophan and tyrosine from the blood is chronically reduced, it is likely that long-term adjustments of neurotransmitter metabolism occur in the diabetic brain. PMID- 2887081 TI - Primidone and propranolol in essential tremor: a study based on quantitative tremor recording and plasma anticonvulsant levels. AB - Primidone was compared to the unselective beta adrenoceptor antagonist propranolol in the suppression of essential tremor. In a 4-week single-blind placebo-controlled study primidone was given in increasing doses from 62.5 mg X 1 up to 250 mg X 3 daily and propranolol 20 mg X 3 daily. The drugs produced a similar reduction in the degree of tremor after 2 and 1 weeks' medication respectively. This indicates that primidone can be an alternative to propranolol when beta-blockers are contraindicated. However, primidone was significantly even more effective in the beginning after only 2 doses, when at the same time 10 of 13 patients showed a maximum of acute toxic side-effects producing nausea, vomiting, giddiness and/or sedation. Correlation analysis between the individual tremor amplitude reductions and plasma primidone concentrations showed on the second day a tendency towards a greater reduction in tremor in those patients with the highest primidone plasma concentration. By the fourteenth day tremor had increased compared with the second day and correlation analysis between individual increase in tremor amplitude and plasma phenobarbital concentrations showed the highest degree of tremor increase in those patients who had the highest levels of phenobarbital. These and other data suggest that after the first doses, tremor suppression and acute toxicity is related to the initial exposure to primidone and the plasma level of the drug itself rather than its metabolites phenobarbital and phenylethylmalanomide. The individual tremor frequency spectrums did not change significantly during the placebo and propranolol periods, whereas the frequency tended to decrease during the primidone period. PMID- 2887082 TI - Paragangliomas of the craniocervical region. An immunohistochemical study on tyrosine hydroxylase. AB - An immunohistochemical study on tyrosine hydroxylase (TH), a rate-limiting enzyme in the catecholamine synthesizing pathway, was made on three craniocervical region paragangliomas, two of which showed metastases to the cervical lymph nodes. In all of the original tumors, the majority of tumor cells showed positive immunostaining for TH of variable intensity in their cytoplasm regardless of their cytological features such as cellular and nuclear pleomorphism. The finding suggests that most tumor cells are capable of production of catecholamines and are derived from chief cells in the normal paraganglia. In cervical lymph nodes, however, no positive immunostaining for TH was observed in metastatic tumor cells, in contrast with the findings in the original tumors. The absence of TH immunoreactivity in metastatic tumor cells appears to be noteworthy in considering their malignant potential. Application of the TH immunohistochemistry to further cases appears important for the better understanding of this neoplasm, a catecholamine-producing tumor. PMID- 2887083 TI - Tissue reactions to implanted orthodontic wires in rabbits. AB - Tissue response to a Fe-Cr-Ni and a Co-Cr-Ni orthodontic wire, in the as-received state and with silver soldered joints, was investigated. Specimens with polytetrafluoroethylene (PTFE) as a reference material were implanted in the subcutaneous tissue of rabbits. Six rabbits were sensitized to nickel, four animals were sham-sensitized, and two were left untreated. The results showed that the as-received wires gave no tissue response relative to the PTFE control. In soldered specimens that were moderate to extreme reactions adjacent to the soldered joint and around the wire portion as well. The soldered Co-Cr-Ni wire elicited the most severe reactions, most pronounced in the nickel-sensitized animals. The agar overlay cell culture test of some retrieved implants showed pronounced cytotoxicity of the soldered specimens. Leachable toxic components of the silver solder seemed to be of major importance in the observed cell culture and tissue response to the soldered specimens. PMID- 2887084 TI - Partial characterization of a peptidoglycan-protein complex from Fusobacterium nucleatum Fev1. AB - A protein in the cell wall of Fusobacterium nucleatum Fev1 remained associated with the peptidoglycan during extraction with various detergents and organic solvents. On digestion of this peptidoglycan-protein complex (PPC) with murein hydrolases, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed polypeptide bands with apparent molecular weights (MWs) in the range of 3000 to 40,000. After reaction with maleic anhydride the electrophoretic mobilities of these polypeptide bands increased to those of MWs 3000 to 12,000. The PPC protein showed a limited susceptibility toward trypsin, giving polypeptides that migrated in SDS-PAGE as a diffuse band with MW in the range of 3000 to 6000. The amino acid composition of all polypeptide bands eluted from SDS PAGE was very similar, whichever enzyme was used for the solubilization of the PPC, and was nearly identical to that found for the protein moiety of the PPC. On the basis of a MW of 3000 for a protein unit, about one molecule of protein was found per five peptidoglycan subunits. Lanthionine was not found associated with released polypeptide, and muramic acid and glucosamine were either absent or present in amounts less than one molecule per protein unit. The PPC was immunogenic in rabbits, and purified anti-PPC IgG reacted with murein hydrolase released protein separated on SDS-PAGE but preferentially with bands of MWs greater than 18,000. PMID- 2887085 TI - [New concepts and methods in the study of anti-myocardial ischemia drugs]. PMID- 2887086 TI - Influence of nonselective beta-adrenergic impacts on the effects of thrombocytopoietin in mice. AB - The effects of plasma thrombocytopoietin are investigated in test mice against the background of nonselective beta adrenergic impacts. The changes in the thrombocytopoiesis are accounted for by the thrombocytes count and by the percentage of 75selenomethionine incorporated in the newly-formed thrombocytes. Plasma thrombocytopoietin is found to stimulate markedly thrombocytopoiesis on the background of beta-adrenergic stimulation with isoprenaline. Pretreatment with propranolol totally prevents this stimulation. Independent treatment with propranolol as a background of thrombocytopoietin considerably inhibits thrombocytopoiesis. The effects of thrombocytopoietin are found to depend on the state of the beta-adrenoreceptors: their stimulation has a synergic effect on thrombocytopoietin, while their blocking impedes its realization. The data established are indirect proof about the existence of beta-adrenoreceptors in the megakaryocyte series and probably in its precursors as well. PMID- 2887087 TI - [Open study of clotiazepam (Clozan) in ambulatory anxious patients centered on a multifactorial evaluation using the AMDP and on a study of the rebound effect]. AB - The efficacy and tolerance of the first thienodiazepine, clotiazepam, is well established but its clinical spectrum and the possibility of a rebound effect upon its cessation needed further research. Moreover, the validity of the AMDP Anxiety scale had been tested but not yet its sensitivity to change. Clotiazepam was given in an "open" design to 42 anxious outpatients at the dosage of 3 X 5 to 3 X 10 mg daily during 1 month, followed by a 1-week "single blind" placebo period. No other psychotropic drug was needed in 74% of the cases. A battery of observer rating scales (CGI, VAS, HAMA, BPRS, AMDP-4 and -5, AMDP-AT) confirmed the anxiolytic and tensiolytic efficacy of clotiazepam as well as its excellent tolerance. The 13-factor AMDP profile proved superior to short scales in the sample description and in the illustration of the clinical spectrum of the drug. Both the HAMA and the AMDP-AT were sensitive to change but the HAMA more significantly than the AMDP-AT. PMID- 2887088 TI - Neuroleptic treatment and other factors modifying cancer risk in schizophrenic patients. AB - In a Danish cohort of schizophrenics consisting of 6,168 patients followed during 1957-1980, the incidence of certain types of cancer has been shown to be significantly decreased (5). From this cohort 30 males with lung cancer, 21 males with bladder cancer, 17 females with cancer of the uterine cervix and 40 females with breast cancer, were each matched to two "healthy" schizophrenic controls from the same cohort. A range of social, demographic and nosocomial factors were registered from the individual case files, and statistical analysis was carried out, using Cox's regression model. Neuroleptic treatment with various drugs other than reserpine reduced the risk of developing all four cancer types studied. In contrast reserpine treatment increased the risk of developing cancer of the breast and uterine cervix. Furthermore, cancer risk was found to be modified by other well-known risk factors. PMID- 2887090 TI - The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic treated patients. PMID- 2887091 TI - [Orchidopexy with the Dartos technic. Results in 187 cases]. PMID- 2887089 TI - Peripheral markers in the female "hidden alcoholic". AB - Mean corpuscular volume, thrombocyte count and levels of gamma glutamyltransferase, aspartate aminotransferase, albumin, urate, and triglycerides were analyzed in 100 previously untreated female alcoholics. If used for screening, urate and triglycerides were found to be of no value, while various combinations of the other biochemical markers identified up to 75% of the patients. PMID- 2887093 TI - Acute hantavirus nephropathy in Belgium: preliminary results of a sero epidemiological study. PMID- 2887092 TI - HPLC of neurotransmitters and their metabolites. PMID- 2887095 TI - Takayasu's arteritis of the aortic arch: endovascular treatment and correlation with positron emission tomography. AB - A case is presented in which three arterial stenoses and one arterial occlusion due to Takayasu's disease were treated by an endovascular approach. The endovascular technique is discussed, and the clinical and angiographic findings after treatment are correlated with cerebral hemodynamic and metabolic parameters as measured by positron emission tomography. PMID- 2887094 TI - [Organic male impotence]. PMID- 2887096 TI - Interventions that potentially limit myocardial infarct size: overview of clinical trials. AB - Theoretically, interventions that restore the balance between oxygen supply and demand when given during the early hours of a heart attack may reduce infarct size and prevent fatal arrhythmias and thereby prolong survival. Data on mortality from the available randomized trials of thrombolytic therapy, intravenous beta blockers, hyaluronidase, intravenous nitrates and calcium channel blockers in acute myocardial infarction, are systematically reviewed. Analyses confirm that intravenous streptokinase reduces mortality by about 25% but suggests that measures to prevent reinfarction may be required after thrombolytic therapy. beta blockers reduced mortality by approximately 15%. The pooled data from the existing trials of hyaluronidase and intravenous nitrates are consistent with a 15% to 20% decrease in mortality; ideally this should be confirmed in future large randomized trials. Currently, there is no evidence either from individual studies or the aggregate of all the trials that calcium channel blockers reduce mortality. The collective experience from the trials carried out over the last 2 decades suggests that most interventions in acute myocardial infarction have, at best, only moderate effects with a 10% to 20% reduction in mortality. Current and future trials that assess the effects of cardiovascular treatments on mortality should therefore aim to randomize 10,000 to 20,000 average risk patients or a few thousand high risk patients. PMID- 2887097 TI - Efficacy of nifedipine and metoprolol in the early treatment of unstable angina in the coronary care unit: findings from the Holland Interuniversity Nifedipine/metoprolol Trial (HINT). AB - A multicenter, double-blind, placebo-controlled, randomized trial of nifedipine, metoprolol and their combination was conducted in 338 patients with unstable angina (hospital admission diagnosis) who had not previously received treatment with a beta blocker. In addition, nifedipine was compared with placebo in 177 patients who were receiving beta blockers upon hospital admission. The main outcome event was the recurrence of ischemia or progression to myocardial infarction within 48 hours. Trial medication effects are expressed as ratios of event rates relative to placebo, e.g., for nifedipine as the event rate under nifedipine divided by that under placebo; 95% confidence intervals are also given. In patients not pretreated with a beta blocker the rate ratio for nifedipine was 1.15 (0.83, 1.64), for metoprolol 0.76 (0.49, 1.16) and for the combination 0.80 (0.53, 1.19). In patients already receiving a beta blocker, the addition of nifedipine was favorable and the rate ratio was 0.68 (0.47, 0.97). Equal numbers of patients developed myocardial infarction and reversible ischemia. Most infarctions occurred early, within 6 hours of randomization. In patients who were not already taking a beta blocker, the nifedipine rate ratio for infarction only was 1.51 (0.87, 2.74). These results suggest that, in patients not previously receiving beta blockers, metoprolol has a beneficial short-term effect on unstable angina, that a fixed combination with nifedipine provides no further gain and that nifedipine may be ineffective or counterproductive. On the other hand, the addition of nifedipine to existing beta blockade when the patient becomes unstable seems beneficial. PMID- 2887099 TI - Choice of therapy in chronic ischemic heart disease. AB - The choice of therapy in chronic ischemic heart disease depends on identifying the underlying mechanism. Ambulatory monitoring provides a means of identifying those patients in whom increased myocardial oxygen demand is the most important mechanism and who will respond to a beta blocker. In contrast, those patients with coronary spasm are best treated with a calcium antagonist. The history of angina pectoris and the time of onset may, in itself, be misleading. Detailed ambulatory monitoring studies show that nocturnal angina is frequently due to increased myocardial oxygen demand and in such circumstances should be treated by careful control of the heart rate using a beta blocker without intrinsic sympathomimetic activity. Other factors that will influence the choice of medical therapy must be considered. Smoking is particularly important because it not only acts detrimentally in terms of increased myocardial oxygen demand, but may also interfere with the metabolism of those antianginal agents that are metabolized in the liver. The importance of silent myocardial ischemia has been emphasized recently, and studies using ambulatory pulmonary artery monitoring have shown that silent ischemic episodes have the same significance in terms of hemodynamic effects as painful ischemic episodes. The therapeutic and prognostic implications of these findings need to be explored. PMID- 2887100 TI - Beta blockade early in acute myocardial infarction. AB - Intravenous beta blockers given early in acute myocardial infarction have been shown to reduce chest pain, enzyme release and incidence of arrhythmias. Data published before the first report of the ISIS-1 group (International Studies of Infarct Survival) showed a 12% decrease in the probability of death using intravenous beta blockade but with large confidence limits. This study assessed and compared the effects of early intravenous atenolol and control treatment in the first week and first year after acute myocardial infarction in 16,027 patients. The principal endpoint was vascular death; most of the 15% decrease in mortality occurred in the first 24 to 36 hours with a significant difference at 1 week (313 vs 365 deaths in the atenolol and control groups, respectively). There was no rebound effect after stopping treatment after 7 days. Mortality at 1 year also showed a significant difference in favor of the atenolol group. Subgroup analysis found no significant difference in mortality by age, sex, initial heart rate, diabetes or entry electrocardiogram but data-derived analysis revealed a highly significant decrease in mortality if treatment began within 2 hours of the onset of pain. There was a significant 1% to 2% excess in inotrope use in the atenolol group in the first 36 hours, and first-degree heart block and bundle branch block emerged as relative contraindications to this treatment. The results suggest that early intravenous beta blockade in acute myocardial infarction is safe and effective and also cost effective in comparison with postdischarge oral beta blockade therapy. PMID- 2887098 TI - Secondary prevention trials after acute myocardial infarction. AB - Of those patients who reach the hospital after an acute myocardial infarction, 18% die during their stay and 85% to 90% of the remainder will eventually die of coronary artery disease. Several secondary preventive approaches have been made to prolong life in these patients. Long-term controlled trials involving nonsurgical measures and at least 100 patients will be reviewed. Lipid-lowering regimens have shown no demonstrable effect on survival over a 4- to 6-year period but show some benefit with respect to nonfatal infarction. Survival was not improved essentially by anticoagulants, antiarrhythmic agents or calcium channel blockers, although new trials are underway that might clarify their role. Platelet-active drugs achieved little reduction in mortality but showed benefit in nonfatal infarction (30% reduction with aspirin). Pooled data on physical exercise programs demonstrated a 15% benefit on mortality but larger trials are required to confirm this. The data on beta blockers (particularly those without intrinsic sympathomimetic activity) show that these drugs improve long-term survival after myocardial infarction, reducing all-cause mortality by as much as 25% to 30%. Larger trials are necessary to detect statistically significant reductions in mortality both overall and in selected subgroups of patients. PMID- 2887101 TI - Comparison of selective (beta 1) and nonselective (beta 1 and beta 2) beta adrenergic blockade on systemic and coronary hemodynamic findings in angina pectoris. AB - To investigate the influence of selective beta 1-adrenergic blockade, in contrast to beta 1- and beta 2-adrenergic blockade, systemic and coronary hemodynamics were studied. Measurements were made at rest and during exercise in 23 patients with suspected coronary artery disease (CAD) before and after either metoprolol or propranolol, given in doses to provide comparable beta 1-receptor blockade. Quantitative coronary angiography was performed at rest. Using a randomized, double-blind protocol, either beta 1 and beta 2 blockade was produced by propranolol (0.1 mg/kg intravenously), or selective beta 1 blockade was produced by metoprolol (0.15 mg/kg intravenously). As expected, at these doses both drugs produced a comparable decrease in heart rate at rest and during exercise, averaging 9% and 14% after propranolol and 10% and 16% after metoprolol. Exercise duration to ischemia was prolonged in most patients with severe CAD after either propranolol (5 of 7) or metoprolol (6 of 10) treatment. The effects of these 2 beta-blocking drugs on systemic hemodynamic values at rest and during exercise were similar. Additionally, coronary sinus flow was usually unchanged by both drugs at rest (-5% after propranolol and -4% after metoprolol, differences not significant) and decreased a similar amount during exercise (-15% after propranolol and -9% after metoprolol, both p less than 0.05). Coronary resistance did not change significantly with either drug (0% after propranolol and 3% after metoprolol), and during exercise (11% after propranolol and 3% after metoprolol), suggesting that decreases in flow were secondary to reduced demand. Furthermore, neither drug produced detectable changes in coronary artery size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887102 TI - Chronic effects of direct vasodilation (pinacidil), alpha-adrenergic blockade (prazosin) and angiotensin-converting enzyme inhibition (captopril) in systemic hypertension. AB - Chronic responses of systemic hemodynamics and blood pressure counterregulatory ("pseudo-tolerance") mechanisms were investigated in matched groups of patients with essential hypertension after 1 month of vasodilator therapy with pinacidil (a direct arterial dilator), prazosin (an alpha 1-adrenergic blocking drug) or captopril (an angiotensin-converting enzyme inhibitor). For equivalent decreases in mean arterial pressure compared with placebo baseline (approximately 8 mm Hg supine and 12 mm Hg upright), prazosin and captopril did not increase cardiac index or heart rate. In contrast, marked decreases in systemic vascular resistance with pinacidil (approximately 25%, p less than 0.05) were accompanied by reflex increases in cardiac index (approximately 20%, p less than 0.05). Activity of the sympathetic nervous system, measured by supine and upright plasma norepinephrine (NE), increased approximately 50% with pinacidil and prazosin (p less than 0.001 each), whereas captopril decreased supine plasma NE by 12% (p less than 0.05) and did not change upright plasma NE. All 3 drugs caused an expansion of height-adjusted blood volume (approximately 14%). Pinacidil and prazosin caused reversible weight gains of 0.9 and 0.7 kg, respectively, whereas captopril reversibly decreased body weight by 0.8 kg (p less than 0.05), suggesting differential effects of the 3 drugs on interstitial fluid volume. During chronic therapy, all 3 drugs may require concomitant diuretic therapy, whereas concomitant sympatholytic therapy may be required with the potent vasodilator pinacidil. Captopril may be associated with the lowest cardiac risk because of its lack of stimulatory effects on the sympathetic nervous system and cardiac index. PMID- 2887103 TI - Enzyme histochemistry of the rat nasal mucosa embedded in cold glycol methacrylate. AB - The nasal passages are anatomically complex, and while there have been a number of descriptions of nasal structure in many species, there is very little information available on the distribution of enzymes in the nasal mucosa. In rodents, this delicate mucosa is the first site within the respiratory tract to be exposed during inhalation toxicology studies designed to assess human risks from such exposures. However, the nasal mucosa presents problems for histologic preparation because it is encased in brittle bones. Because of recent interest in the nose as a target site, and findings from biochemical studies which indicate that the nose is very active metabolically, studies were carried out to determine the value of cold glycol methacrylate (GMA) processing for localization of nasal enzymes. For these studies, liver and kidney were used as positive controls. Published histochemical procedures for acid and alkaline phosphatase, adenosine triphosphatase, glucose-6-phosphatase, gamma-glutamyl transpeptidase, and naphthyl butyrate esterase were applied, with modifications, to undecalcified nasal passages of Fisher-344 rats. Frozen sections exhibited excellent enzyme preservation but very poor morphology, while GMA gave good enzyme preservation and excellent morphology. For GMA, acetone fixation generally resulted in the best preservation of enzyme activity. It was concluded that cold GMA processing provides a useful approach to studies of nasal enzyme distribution and that this technique of value for inhalation toxicology studies. Details of enzyme distribution in the squamous, respiratory, and olfactory epithelia, associated glands, and other structures of the nose of the rat are described and discussed. PMID- 2887104 TI - Multiple islet cell tumors with predominance of glucagon-producing cells and ulcer disease. AB - Two cases of multiple islet cell tumors mostly composed of glucagon-producing cells and associated with severe ulcer disease are presented. Multiple endocrine neoplasia type I (MEN-I) was present in both patients, although symptomatically latent in case 2. Immunohistochemistry showed that glucagon (A) cells were a major cell population (i.e., accounting for at least 30% of the tumor cell population) in 24 of 43 tumors (either macroadenomas or microadenomas) studied in case 1 and in 12 of 17 tumors studied in case 2. A major pancreatic polypeptide (PP) cell population was found in 12 and 7 tumors of case 1 and 2, respectively. In contrast, insulin (B) and somatostatin (D) cells were scarce in most adenomas. Gastrin-producing cells were not identified in any tumors, despite the use of different antigastrin antisera. Extrapancreatic or residual gastrinomas were not found at postmortem examination in case 1 or on appropriate surgical inspection done 24 years after the onset of the ulcer disease in patient 2. On the basis of these and of 17 additional cases collected in the literature, it is concluded that multiple A-cell tumors of the pancreas are an expression of the MEN-I and are mostly associated with ulcer disease and/or with hypergastrinemia of frequent uncertain origin. The mechanisms regulating the nonrandom phenotypic hormonal differentiation of these genetically determined tumors remain unknown. PMID- 2887105 TI - Soft-tissue infections caused by Mycobacterium fortuitum complex following penetrating injury. AB - Soft-tissue infections caused by rapidly growing mycobacteria may follow penetrating trauma. We present four immunologically normal patients in whom soft tissue infections with Mycobacterium fortuitum developed after they stepped on nails. Their presentations were clinically indistinguishable from puncture wound infections caused by Pseudomonas aeruginosa and Staphylococcus aureus. The acid fast organisms grew on standard bacteriologic media within three to five days. Speciation and antimicrobial susceptibility testing was performed. The primary mode of therapy was surgical; adjunctive antimicrobial therapy is recommended only for extensive or chronic infections and in immunocompromised hosts. All four of our patients had good outcomes after therapy. PMID- 2887106 TI - Clinical effects of accidental levothyroxine ingestion in children. AB - Forty-one children, aged 1 to 5 years, who accidentally ingested levothyroxine sodium were studied. Symptoms possibly associated with the ingestion occurred in 11 patients (27%). These symptoms (tachycardia, hyperactive behavior, fever, vomiting, diarrhea, diaphoresis, and flushing) were categorized as minor and all resolved without treatment. Because observed effects were generally mild and often unrelated to either estimated amounts of hormone consumed or serum thyroxine levels, a conservative approach to patient treatment is recommended in cases of levothyroxine ingestion in children. PMID- 2887107 TI - Epidemiologic aspects of a St. Louis encephalitis outbreak in Mesa County, Colorado. AB - An epidemic of St. Louis encephalitis in 1985 in Mesa County, Colorado, led to 17 cases, including one fatality. Risk was associated with advanced age and residence in Grand Junction, the county's principal city. A trend was observed toward higher risk in females. However, increased risk in females was not associated with higher infection rates (increased exposure). Capture enzyme immunoassays detected specific immunoglobulin M (IgM) and immunoglobulin A after infection. A serosurvey of Grand Junction residents disclosed an infection rate of 4.0%, indicating that 1,123 epidemic St. Louis encephalitis infections may have occurred in the city. Evidence of previous St. Louis encephalitis virus infection was found in 11.2% of survey respondents who had neutralizing antibody to the virus without specific IgM. The prevalence of St. Louis encephalitis virus antibody was similar to rates observed in serosurveys undertaken 30 years earlier, indicating that the level of endemic St. Louis encephalitis transmission in the city had not changed appreciably in that interval. PMID- 2887108 TI - Application of DNA polymorphisms for prenatal diagnosis of beta thalassemia in Chinese. AB - Forty-seven Chinese suffering from beta thalassemia major and their parents were studied to establish linkage of the beta thal and beta A genes with 11 restriction site polymorphisms. There is marked linkage disequilibrium at the BamH I site 3' to the beta globin gene, such that, in 31% of pregnancies, absence of the site in the fetus can exclude beta thalassemia major. Using four restriction sites (Hinc II psi beta, Ava II beta, Hind III beta, and BamH I beta), prenatal diagnosis is feasible in all families. In 46% of all cases, a definitive diagnosis can be made, and in the remaining cases, a 50% chance of exclusion is possible. Fetal blood globin chain analysis would be required for the failures. Our experience in nine successive beta thalassemia prenatal diagnosis is also reported. PMID- 2887109 TI - Haplotypes identified by DNA restriction-fragment-length polymorphisms in the A-1 C-III A-IV gene region and hypertriglyceridemia. PMID- 2887111 TI - Formulas for mean restriction-fragment lengths and related quantities. PMID- 2887110 TI - Familial inheritance of a DXS164 deletion mutation from a heterozygous female. AB - Restriction-fragment-length-polymorphism analysis was used to examine a female who is segregating for Duchenne muscular dystrophy (DMD) and a deletion of the DXS164 region of the X chromosome. The segregating female has no prior family history of DMD, and she has two copies of the DXS164 region in her peripheral blood lymphocytes. The following two hypotheses are proposed to explain the coincidence of the DMD phenotype and deletion of the DXS164 region in her offspring: (1) she may be a gonadal mosaic for cells with two normal X chromosomes and cells with one normal X chromosome and an X chromosome with a deletion of the DXS164 region; and (2) she may carry a familial X;autosome translocation in which the DXS164 region is deleted from one X chromosome and translocated to an autosome. The segregation of DMD and the DXS164 deletion in this family illustrates the importance of extended pedigree analysis when DXS164 deletions are used to identify female carriers of the DMD gene. PMID- 2887112 TI - Misoprostol in the treatment of duodenal ulcer refractory to H2-blocker therapy. A placebo-controlled, multicenter, double-blind, randomized trial. AB - A multicenter, double-blind, randomized study compared 200 micrograms of misoprostol and placebo four times daily for four weeks in the treatment of 225 patients with duodenal ulcer (0.7 cm to 2.0 cm in size) persisting after at least four weeks of adequate, conventional therapy with cimetidine or ranitidine. Misoprostol was significantly superior to placebo in healing duodenal ulcers (achieving a healing rate of 37 percent versus 22 percent in the placebo group [p = 0.02], and in relieving ulcer pain [p = 0.01]). Healing also occurred more frequently with misoprostol than with placebo in patients with subgroups of particularly resistant ulcers. In the treatment of ulcers refractory to at least eight weeks of histamine H2-blocker therapy, misoprostol achieved a healing rate of 42 percent versus 20 percent with placebo. In the treatment of pyloric channel ulcers, 28 percent of patients in the misoprostol group showed healing as compared with 20 percent in the placebo group. Diarrhea was reported by 15.4 percent and 3.4 percent of patients receiving misoprostol and placebo, respectively, and was usually mild and transient. Misoprostol is safe and effective therapy for duodenal ulcers that have not healed during the course of H2-blocker therapy. PMID- 2887113 TI - Demonstration of specific E-type prostaglandin receptors using enriched preparations of canine parietal cells and [3H]misoprostol free acid. AB - High-affinity, E-type prostaglandin binding sites in enriched canine parietal cell preparations were identified with [3H] misoprostol free acid, a prostaglandin E1 analogue. Saturable, reversible, and highly stereospecific binding was identified, with approximately 8,000 binding sites per cell. Prostaglandin I and F bound weakly, and cimetidine and histamine did not bind. The results indicate that [3H] misoprostol free acid binds to E-type prostaglandin receptors, which suggests that the ulcer-healing inhibition of gastric acid secretion by misoprostol results from its interaction with a specific E-type prostaglandin receptor. PMID- 2887114 TI - Prevalence of major depressive disorder in patients receiving beta-blocker therapy versus other medications. AB - Depression is believed to be a common side effect in patients receiving beta blocker therapy. However, diagnoses of depression defined by current diagnostic criteria may not be more common in patients receiving beta-blockers than in patients with the same medical disorder receiving other medications. Seventy seven patients undergoing elective cardiac catheterization for evaluation of chest pain received a semi-structured diagnostic psychiatric interview. Twenty one percent of the patients receiving beta-blockers and 33 percent of the patients receiving medications other than beta-blockers met the current American Psychiatric Association criteria for major depressive disorder (DSM-III) (p = NS). The mean heart rate and state anxiety scores for patients taking beta blockers were significantly lower than those measured in patients taking medications other than beta-blockers. No other medical or demographic differences were observed between the two groups. Despite the methodologic limitations of the study, there does not appear to be a difference in the point prevalence of depression between patients receiving beta-blockers and those receiving other medications. PMID- 2887115 TI - Mitral valve prolapse with symptoms of beta-adrenergic hypersensitivity. PMID- 2887116 TI - gamma-Glutamyl transferase and mean cell volume reveal maternal alcohol abuse and fetal alcohol effects. AB - Serial measurements of gamma-glutamyl transferase and mean cell volume were done in 85 pregnant alcohol abusers (320 samples). These included 26 moderate drinkers, 30 heavy drinkers, and 29 alcoholic women. Studies of 28 pregnant women who denied the use of alcohol (138 samples) showed that pregnancy itself had no effect on gamma-glutamyl transferase and mean cell volume. However, gamma glutamyl transferase was increased in 14.9%, 31.7% and 59.1% of the samples collected from moderate drinkers, heavy drinkers, and alcoholic women, respectively, and likewise mean cell volume was elevated in 10.8%, 17.2%, and 40.2%, respectively. Either gamma-glutamyl transferase or mean cell volume was high or both were high in 27.1% of the moderate drinkers, in 38.3% of the heavy drinkers, and in 76.3% of the alcoholic women. Fetal alcohol effects developed in 42 cases. Increased gamma-glutamyl transferase predicted fetal alcohol effects in 61.5%, with a relative risk of 2.51. Elevated mean cell volume predicted fetal alcohol effects in 40.9%, with a relative risk of 2.40. These results suggest that the assay of gamma-glutamyl transferase and mean cell volume can be valuable in monitoring pregnant women with recognized or suspected alcohol abuse. PMID- 2887117 TI - Reflex decreases in intragastric pressure in response to cholecystokinin in rats. AB - The actions of intravenous sulfated cholecystokinin octapeptide (CCK-8) on intraluminal pressure in the body of the stomach were studied in urethan anesthetized rats. There was a dose-related decrease in pressure in response to CCK-8 over the range 0.3-33 pmol. Bilateral cervical vagotomy alone reduced the response to CCK-8 and together with splanchnic section abolished it. Hexamethonium also reduced the response. Vagotomy did not change the response to CCK-8 in hexamethonium-treated rats, but celiac ganglionectomy abolished it. Guanethidine and phentolamine, but not propranolol, significantly decreased the response to CCK-8; subsequent vagotomy abolished the response. Similarly, depletion of tissue catecholamines by pretreatment with 6-OH dopamine, reserpine, or celiac ganglionectomy together with vagal section abolished the effect of CCK 8. It concluded that CCK-8 decreases mean intragastric pressure in the rat by pathways involving both vagal and splanchnic nerves. The splanchnic pathway involves an alpha-adrenergic mechanism but is hexamethonium resistant. The vagal pathway is hexamethonium sensitive and nonadrenergic. Similar pathways may mediate the effect of CCK on gastric emptying. PMID- 2887118 TI - Effect of gastrin-releasing peptide analogues on gastrin and somatostatin release from isolated rat stomach. AB - A differential biological potency of bombesin (BBS), compared with its mammalian counterpart gastrin-releasing peptide (GRP), has been reported in several biological systems in rodents. In the present study we have examined the relative potency of BBS, GRP-(1-27) (GRP-L), and GRP-(14-27) (GRP-S) on the release of gastrin and somatostatin (SRIF) from the isolated perfused rat stomachs. Male rats were fasted overnight and the stomachs perfused via the celiac artery. Increasing doses of BBS, GRP-L, and GRP-S were perfused for 15 min each and the effluent collected for measurement of gastrin and SRIF. The release of gastrin and SRIF in response to the GRP analogues was biphasic, with a peak increase occurring within the first 5 min, followed by a sustained increased secretion. The release of gastrin in response to 10(-10)-10(-9) M concentrations of the peptides was strongest with GRP-S (1.5-2.0 times higher than that released by BBS and GRP-L), although at higher concentrations (10(-8) M), the response to all three analogues was similar. The release of SRIF, on the other hand, was significantly higher in the presence of BBS compared with that in response to GRP S, while GRP-L was ineffective. These studies indicate that the biological potency of BBS compared with its mammalian counterpart, GRP, is different on the two cell populations [gastrin (G) and SRIF (D)]. PMID- 2887119 TI - Role of opioid neurons in the regulation of intestinal peristalsis. AB - The participation of opioid neurons in the regulation of peristalsis was examined in a rat colonic segment that permits separate characterization of the components of the peristaltic reflex (ascending contraction and descending relaxation). Naloxone increased descending relaxation and decreased ascending contraction; opioid peptides [methionine-enkephalin (Met-Enk), dynorphin-13, and morphiceptin] had opposite effects. Naloxone increased, and Met-Enk decreased, vasoactive intestinal peptide (VIP) release during each component of the reflex. The changes in VIP release reinforced the direct effects of naloxone and opioid peptides on circular muscle tone, providing an explanation for the effects of these agents on the two components of the peristaltic reflex. Dynorphin release decreased during descending relaxation and increased during ascending contraction, reflecting corresponding changes in opioid neural activity. Based on these results a model is proposed, according to which a decrease in opioid neural activity during the initial phase (i.e., descending relaxation) results in direct and VIP-mediated decrease in circular muscle tone. Restoration of opioid neural activity during the subsequent phase (i.e., ascending contraction) increases circular muscle tone and reinforces the action of tachykinin and cholinergic motor neurons, which are the direct mediators of ascending contraction. PMID- 2887120 TI - Selective inhibition of endothelium-dependent dilation in resistance-sized vessels in vivo. AB - In vivo experiments were performed in autoperfused hindlimbs of rabbits to investigate the role of endothelium-mediated vasomotion in resistance-sized vessels. The flow responses to the vasodilators acetylcholine (ACh), ATP, and substance P (SP), all of which have been shown to act in an endothelium-dependent manner in large conduit arteries, were studied before and after exposure of the hindleg vasculature to gossypol (a potent inhibitor of endothelium-mediated vasodilation in vitro). The flow responses to adenosine (ADO), nitroglycerin (GTN), and prostaglandin E2 (PGE2), which induce relaxation by a direct effect on vascular smooth muscle, were tested in the same manner. All vasodilators induced dose-dependent increases in femoral flow up to two- to threefold when administered intra-arterially. After gossypol, the flow responses to the endothelium-dependent compounds (ACh, ATP, and SP) were severely reduced (by 88 +/- 3%, P less than 0.01) or sometimes were converted to constrictions (ATP). The flow increases induced by ADO, PGE2, and GTN remained largely unaffected. Sham treatment (gossypol solute only), exposure to indomethacin (10 microM), and ganglionic blockade had no differential effect on the flow responses. The selective action of gossypol in suppressing the flow responses to the endothelium dependent compounds ACh, ATP, and SP is consistent with a vasomotor role for endothelial cells in resistance-sized vessels in vivo. PMID- 2887122 TI - Coronary vasoconstriction mediated by alpha 1- and alpha 2-adrenoceptors in conscious dogs. AB - Coronary vasoconstriction was examined in response to the selective stimulation of alpha 1- and alpha 2-adrenoceptors in chronically instrumented conscious dogs. Norepinephrine (NE, 0.05 and 0.1 micrograms X kg-1 X min-1), a mixed alpha 1- to alpha 2-adrenoceptor agonist, phenylephrine (PE, 0.5 and 1.0 micrograms X kg-1 X min-1), a preferential alpha 1-adrenoceptor agonist, and B-HT 920 (1.0 micrograms X kg-1 X min-1), a preferential alpha 2-adrenoceptor agonist, were infused intravenously after ganglionic (hexamethonium, 30 mg/kg iv), beta-adrenoceptor (propranolol, 1.0 mg/kg iv), and muscarinic receptor (atropine methylbromide, 0.1 mg/kg iv) antagonism. Equipressor doses of the alpha-adrenoceptor agonists caused similar increases in calculated late diastolic coronary resistance (NE, 0.57 +/- 0.10 mmHg X ml-1 X min; PE, 0.61 +/- 0.13 mmHg X ml-1 X min; B-HT 920, 0.64 +/- 0.09 mmHg X ml-1 X min). Mechanically increasing aortic root pressure to levels similar to those observed in response to alpha-adrenoceptor stimulation did not increase coronary resistance. Preferential antagonism of alpha 1-adrenoceptors with prazosin (1 mg/kg iv) abolished the vasoconstrictor response to PE but had a lesser effect on the response to B-HT 920. Antagonism of alpha 2-adrenoceptors with rauwolscine (alpha-yohimbine, 0.1 mg/kg iv) abolished the vasoconstrictor response to B-HT 920 but had a lesser effect on the response to PE. The response to NE was reduced to a similar degree by either alpha 1- or alpha 2-adrenoceptor antagonism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887121 TI - Effects of alpha-adrenergic blockade on coronary autoregulation in dogs. AB - In alpha-chloralose-anesthetized, open-chest dogs, left coronary blood flow and oxygen extraction were measured at perfusion pressures from 25 to 175 mmHg. Pressure-flow relationships were obtained before and after alpha-blockade with prazosin or alpha 2-blockade with yohimbine in the presence of beta-blockade with propranolol. The efficiency of flow autoregulation with increments in pressure was calculated as the closed-loop gain and as the slope of flow to pressure. In all animals the highest gain and the lowest slope were seen when pressure increased from 75 to 125 mmHg. In the prazosin group before alpha-blockade the gain with this pressure increase was 0.76 +/- 0.05, whereas in the yohimbine group before alpha-blockade this gain was 0.75 +/- 0.03. Prazosin reduced the gain within the pressure range of 75-125 mmHg by 41%, and this reduction was statistically significant (P less than 0.05). Prazosin also significantly increased the flow to pressure slope within this range. In addition, at all pressures greater than or equal to 50 mmHg, the level of coronary flow was significantly increased by prazosin. The increase in flow and the reduction in autoregulatory efficiency with prazosin were not attributable to an increase in myocardial oxygen consumption. Yohimbine had no effects on the level of coronary flow or on the autoregulatory efficiency. These data indicate that an alpha 1 adrenoceptor mediated coronary constriction modulates coronary autoregulation. PMID- 2887123 TI - Efficacy of an H1 antagonist, astemizole, for chronic allergic rhinitis. AB - Astemizole, a new histamine H1 receptor antagonist, was tested in a double-blind cross-over comparison study with chlorpheniramine maleate, a very effective conventional H1 antagonist, in patients with chronic allergic rhinitis. Astemizole was found to be equally effective, yet there was a significant decrease in the side effects of sleepiness (P less than .01) and dry mouth (P less than .05). Astemizole has a completely different structure and binding curves from terfenadine. It is approved for clinical use in the United Kingdom, Canada, and many European countries. PMID- 2887124 TI - [Clinico-hormonal characteristics and treatment of the neuropsychological form of the premenstrual syndrome]. PMID- 2887125 TI - [Gamma-glutamyltransferase isoenzymes in healthy pregnant women]. PMID- 2887126 TI - [Treatment of eclamptic convulsions with the so-called lytic cocktail]. PMID- 2887127 TI - Somatostatin, anaesthesia, and the carcinoid syndrome. Peri-operative administration of a somatostatin analogue to suppress carcinoid tumour activity. AB - A patient with carcinoid syndrome on long-term antiserotonin therapy with parachlorophenylalanine, experienced a flushing attack with hypotension during the prophylactic administration of aprotonin prior to the induction of anaesthesia. When she was subsequently prepared with a long-acting somatostatin analogue, octreotide (Sandostatin, Sandoz SMS 201-995), plasma levels of tumour released hormones were reduced and anaesthesia for resection of hepatic metastases was uneventful. The advantages of an anaesthetic approach based on inhibition of carcinoid tumour activity, rather than antagonism of released hormones, are discussed. PMID- 2887128 TI - Beta blockade, suxamethonium and potassium. PMID- 2887129 TI - A rapid assay method for ammonia using glutamine synthetase from glutamate producing bacteria. AB - A rapid enzymatic assay method for ammonia was developed by using glutamine synthetase from glutamate-producing bacteria together with pyruvate kinase, lactate dehydrogenase, and NADH. The time required for determination of 25 nmol of ammonia was 5 min with 1 unit of glutamine synthetase, as opposed to 14-30 min with 1 unit of glutamate dehydrogenases from various sources. The present method was used to determine ammonia in serum, microbiol-culture broth, and waste water. The method can be modified for spectrophotometry in the visible region by substituting pyruvate oxidase, peroxidase, and appropriate chromogens for lactate dehydrogenase and NADH. With 4-aminoantipyrine (4AA) and phenol, and with 4AA and N-ethyl-N-2-hydroxyethyl-m-toluidine as chromogens, the sensitivity of ammonia determination was 0.65 and 1.7 times that with glutamate dehydrogenase, respectively. The present method was also applicable to the continuous detection of the activity of some ammonia-forming enzymes such as guanase, adenosine deaminase, and urease and to the determination of 0.5-30 microM ATP-ADP after some modification of the mixture. PMID- 2887130 TI - Fast atom bombardment mass spectrometry analysis of opioid peptides. AB - Positive and negative ion fast atom bombardment mass spectrometries have been used to determine the amino acid sequence-determining fragment ion information of opioid peptides containing from 5 to 10 amino acid residues. The opioids investigated include several enkephalins, dynorphin A fragments 1-7 through 1-10, and alpha- and beta-neoendorphins. Data obtained in the two ionization polarities provide complementary information and exhibit the C-terminal- and the N-terminal containing amino acid sequence-determining fragment ions that are formed by cleavage of the bond between the carbonyl group and the alpha-carbon (-CHR-CO-), the peptide amide bond (-CO-NH-), and the amino-alkyl (-NH-CHR-) bond. The C terminal sequence ions are dominant in the positive ion mode, whereas the C terminal and N-terminal ions are equally important in the negative ion mode. Detection limits for full mass scans extend down to the picomole range. The apparent role of hydrophobicity of the amino acid residues on the fragmentation characteristics of the peptide is discussed. PMID- 2887131 TI - The Kirschner wire as a readily available tunneling device for the placement of subcutaneous intraspinal narcotic delivery systems. PMID- 2887132 TI - A comparison of the PD35-sGaw and PD20-FEV1 in assessment of the effect of oral anti-allergic compounds on the immediate asthmatic response to inhaled allergen. AB - Assessment of two methods of measuring airway response to allergen challenge showed that results obtained using FEV1 correlated well with those obtained using sGaw irrespective of pre-treatment. Significantly smaller amounts of allergen were required to reduce the sGaw by 35% than to reduce the FEV1 by 20%, although both indices discriminated equally well between the effects of drugs on airway responses to challenge. PMID- 2887133 TI - [Conditions of intubation with vecuronium using a priming principle]. AB - Different protocols based on the priming principle have been proposed so as to enable rapid tracheal intubation with vecuronium. The conditions of such an intubation have been assessed in 47 ASA I or ASA II patients, with an empty stomach, using a priming dose of 0.01 mg X kg-1, followed by a second injection of 0.1 mg X kg-1 after a short interval of 4 min. An intubation score was defined using a nerve stimulator (Relaxograph Datex), by measuring the twitch in comparison with a reference value, as well as time before intubation for four groups of patients. Good intubation scores with a twitch approaching 50% was obtained in all and, in the same way, for a fifth group of patients, intubated in an arbitrary manner 60 s after the second dose of vecuronium. These results can be compared with those obtained by other authors using a different protocol. Nevertheless, this method does not match perfectly that of suxamethonium. Taking into account the side-effects and above all the inhalation risk existing after a priming dose, is it opportune to use this technique for the anaesthesia of a patient with a full stomach? PMID- 2887135 TI - Cigarette smoke makes airway and early parenchymal asbestos-induced lung disease worse in the guinea pig. AB - In order to assess the effects of cigarette smoke and asbestos exposure, we divided guinea pigs into 4 groups: smoking or nonsmoking, and asbestos-exposed or not asbestos-exposed groups. Asbestos-exposed animals were given a single intratracheal instillation of 5 mg UICC amosite, a dose and method of administration that we have previously shown produces morphologic changes in the small airways as well as minimal interstitial fibrosis. Animals were smoked 5 days per week for 6 months. By itself, smoking did not affect lung collagen content, small airways wall thickness, or the volume fraction of tissue surrounding airways, but it did cause a significant increase in alveolar mean linear intercept (Lm). Asbestos alone increased collagen content, airway wall thickness, and tissue volume fraction surrounding airways, the latter measure used to assess interstitial fibrosis. An unexpected finding was that asbestos also increased Lm. The two agents administered together caused more severe changes of all types than were produced by either agent alone, and the interaction between the 2 was generally synergistic. Smoke-exposed animals retained 3 times the asbestos fiber burden of those not smoke-exposed; the increase in retention was greater for short than for long fibers. We conclude that cigarette smoke can potentiate the fibrosis induced by asbestos, possibly because of increased fiber retention. As well, in this model, asbestos or asbestos plus cigarette smoke produces increases in alveolar size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887134 TI - Efficacy of ipecac-induced emesis, orogastric lavage, and activated charcoal for acute drug overdose. AB - The efficacy of ipecac-induced emesis, large-bore orogastric lavage, and activated charcoal as gastrointestinal decontamination procedures after acute drug overdose is unknown. Using an ampicillin overdose model, these three procedures were compared with one another and to a control ingestion in ten human volunteers. Serial serum ampicillin levels were used to compute the areas under the concentration vs time curves (AUC) for each study. The reductions of ampicillin absorption compared to control were as follows: orogastric lavage 32% (NS), ipecac-induced emesis 38% (P less than .01), and activated charcoal 57% (P less than .01). This model examines each intervention in a mutually exclusive fashion. It supports activated charcoal administration as the primary gastrointestinal decontamination procedure after acute drug overdose. PMID- 2887137 TI - [Periarteritis nodosa associated with Horton's disease. Responsibility of hepatitis B viruses]. PMID- 2887136 TI - Extracorporeal shock-wave lithotripsy of gallstones without general anesthesia: first clinical experience. PMID- 2887138 TI - [Takayasu's disease: contribution of percutaneous transluminal coronary angioplasty]. PMID- 2887139 TI - [Tardive dyskinesias of neuroleptics. Major complications of long-term neuroleptic treatment]. PMID- 2887140 TI - [Psychosis of supersensitivity or tardive psychosis of neuroleptics. A complication of long-term neuroleptic treatment?]. PMID- 2887142 TI - Complex loci of Drosophila. PMID- 2887141 TI - Adrenomedullary chromaffin cells as a model to study the neurobiology of ascorbic acid: from monooxygenation to neuromodulation. PMID- 2887143 TI - Proton pumping kinetics and origin of nitrate inhibition of tonoplast-type H+ ATPase. AB - A tonoplast-type vesicle preparation, substantially free from other subcellular membranes, was obtained from corn roots by equilibrium sucrose density gradient centrifugation. At pH 6.5 and in the presence of chloride ions, the tonoplast type ATPase activity as measured by Pi release, was inhibited by nitrate ions. The ATPase activity was insensitive to molybdate and vanadate, indicating a minimum nonspecific phosphatase and plasma membrane contamination. The vesicles exhibited an ATP hydrolysis-supported proton uptake which was measured by the absorption change of acridine orange. The ATP hydrolysis supported uptake and the subsequent perturbant-induced release of protons (decay) was described by a kinetic model which was previously developed to evaluate the coupling between proton pumping and the primary energy yielding process for other biomembranes. The proton pumping activity was more sensitive to nitrate ions then was ATP hydrolysis. The differential effect and the kinetic analysis of nitrate inhibition led us to suggest that (i) the coupling between Pi release and proton pumping was indirect in nature and (ii) the primary inhibitory effect of nitrate ion was originated from an interaction with a protogenic protein domain which is functionally linked to the ATPase in the tonoplast-type membrane. PMID- 2887144 TI - [HTLV-I-associated myelopathy]. AB - Following our proposal of a new clinical entity, HTLV-I-associated myelopathy (HAM), at least 270 cases have now been diagnosed in Japan. The geographical distribution resembles that of adult T-cell leukemia-lymphoma. Our laboratory has now identified 85 cases (27 males and 58 females aged 18-75 [mean 52] yrs. with age at onset 6-75 [mean 37] yrs.). The illness duration ranged from 4 mos. to 55 yrs. (mean 15.6 yrs.). Of the 85 cases, 81 lived in Kagoshima, where about 16% of the population have HTLV-I antibodies. Previously, we recognized a subgroup of cases who had frequent histories of blood transfusion, and from our recent data, 18 (21%) had the same history. The group with no history of transfusion was younger at onset of HAM (33 [SD 18] yrs. vs 49 [12] yrs.; p less than 0.05). From the latter, we have also recognized another subgroup consisting of 6 young cases (under 15 yrs.) whose mothers were positive for HTLV-I antibody titer. This group has been labeled mother-to-child or vertical transmission. Notably, the progression of symptoms was slower in the vertically transmitted group when compared to the group with a history of transfusion. We also reported the effectiveness of corticosteroids in 4 HAM cases and from the present data, 65 cases have been followed up for treatment response. Based on a 14-grade disability scoring, excellent response was noted in 20%, good in 37%, fair in 34% and no response in 9% of the total 65 cases. Compared with the vertically transmitted group, the group a history of blood transfusion appeared to have a better response to corticosteroids. PMID- 2887145 TI - New approaches to managing affective disorders. PMID- 2887146 TI - [Value of beta blockers in the treatment of recurrent ventricular tachycardia in cardiac insufficiency]. AB - Beta-blockers were used to treat 20 patients (mean age 55 +/- 12 years) presenting with severe ventricular arrhythmia on chronic heart failure (NYHA stages II to IV; mean ejection fraction 29.7 +/- 7.8%) due to coronary disease (18 cases) or to cardiomyopathy (2 cases). Ventricular tachycardia sustained (7.6 +/- 6.3 attacks/patient) in 19 patients, unsustained in 18, monomorphous in 8 and polymorphous in 12, had been present for 12.4 +/- 18 months. In all but one hitherto untreated patient, the condition had failed to respond to amiodarone combined with a type Ia (19 patients) and type Ic (16 patients) antiarrhythmic drug. Short-term results were: 17 successes, 2 failures and 1 death due to cardiogenic shock. Fifteen patients were followed up for 14 +/- 6.7 months. Thirteen of them benefited from smaller doses of a formerly ineffective treatment; there was one failure, and one patient in whom the attacks of tachycardia, but not the numerous and polymorphous extrasystoles, were controlled by the beta-blockers suddenly died at night. The actuarial mortality rate was 11.4% as against an expected figure of 30% in such a high risk group. Although no significant changes in ejection fraction were observed, heart failure became worse in 8 patients, but it was compensated by diuretics and/or vasodilators. The effects of beta-blockers in resistant ventricular arrhythmia on heart failure suggest that an adrenergic factor is involved in the mechanism of arrhythmia. Provided treatment is progressive and its haemodynamic consequences carefully monitored, beta-blockade is well tolerated. Its effectiveness on severe arrhythmia and on mortality rate seems to confirm that it prevents sudden death by an anti-arrhythmic mechanism. PMID- 2887147 TI - [Relation between arterial hypertension and plasma lipoproteins: the Australian experience]. AB - In clinical trials the most frequently used anti-hypertensive treatments have been found to produce unfavourable changes in plasma high-density cholesterol lipoprotein (HDL-cholesterol) levels. We have investigated whether such effects could be observed in a general population in which these drugs are often prescribed. This population was divided into three groups: subjects with normal blood pressure, subjects with unrecognized arterial hypertension and subjects receiving an anti-hypertensive treatment. Treatment with beta-blockers of obese hypertensive patients was attended by unfavourable changes identical with those observed in a general population under the most common anti-hypertensive therapy. PMID- 2887148 TI - [Interference with lipid metabolism by various antihypertensive agents: facts and hypotheses]. AB - In view of their effectiveness and safety, beta-blockers and diuretics have become first-line drugs in the treatment of arterial hypertension. Several studies performed over the last few years have elicited undesirable effects of these drugs on plasma lipids and lipoproteins. These changes probably have the same significance as regards the arterial risk as primary or secondary alterations of lipoproteins. In contrast, vasodilators acting by alpha-blockade probably have a favourable effect on lipid metabolism. It therefore seems reasonable, whenever these drugs are prescribed, to carry out regular evaluations of plasma lipids, notably in young subjects to identify those who partly lose the benefit of this treatment owing to a significant degradation of their blood lipid profile. Future epidemiological studies and therapeutic trials should show whether this attitude is right or wrong, their primary objective being to answer the question: do some anti-hypertensive drugs increase, in some subjects, the coronary risk? PMID- 2887149 TI - [Nebulizations of beta-2-adrenergic agents at home in severe asthma in children]. PMID- 2887150 TI - Dose-response of promotion by polychlorinated biphenyls and chloroform in rat liver foci bioassay. AB - Using the rat liver foci bioassay a dose-response relationship was evaluated for the promoting activity of the ubiquitous and persistent environmental pollutants polychlorinated biphenyls (PCBs) and chloroform. Initiation of liver foci was performed by oral administration of a single dose of 8 mg/kg body wt of diethylnitrosamine to weanling female Sprague-Dawley rats. For polychlorinated biphenyls (PCBs) and chloroform a dose-dependent promoting effect was found. The lowest effective dose of PCBs was 1 mg/kg body wt, given three times a week for 11 consecutive weeks. That of chloroform was 100 mg/kg body wt, administered twice a week for 11 consecutive weeks. The livers were screened for preneoplastic foci 12 weeks after starting the experiments. The amounts of PCBs as well as chloroform normally taken up by humans are greater than a factor of 1000 lower than the effective experimental doses. Thus the risk of human exposure to these chemicals is estimated to be very low. In the case of heavy pollution with PCBs, however, as happened in the yusho accident (Japan, 1968), the daily intake of PCBs was in the range of the effective doses used in the experiment. PMID- 2887151 TI - [Peptidergic innervation and the APUD system in normal conditions and in various pathological states]. AB - The use of highly sensitive and selective methods (autoradiography, light and electron microscopy, radioimmunoassay) allowed identification of peptide hormones in both the specialized endocrine cells (apudocytes) of some internal organs and various structural elements of the central and peripheral nervous system. Current knowledge permits one to suggest the existence of a peptidergic innervation as one of the parts of the nervous system and to demonstrate the direct participation of these peptides in the pathogenesis of some diseases. Biological significance of these substances in supporting homeostasis determines the urgent need for a combined investigation of the structural-functional relationship between apudocytes and peripheral nerves under normal and pathologic conditions. This will promote new opportunities in the elucidation of the mechanisms of some pathologic processes. PMID- 2887154 TI - Dental aspects of child abuse: review and case reports. PMID- 2887152 TI - Double-blind study of vigabatrin in the treatment of drug-resistant epilepsy. AB - Thirty-one patients with severe drug-resistant epilepsy entered the study. Vigabatrin (2 to 3 g/d, stratified according to weight) and placebo were administered orally, as add-on therapy in random order under double-blind conditions, each for three months using a crossover design. Thirty patients completed both periods. Of these, ten patients (33%) showed a decrease in seizure frequency of 50% or more. In the 15 patients presenting with complex partial seizures, "temporal" electroencephalographic abnormalities, and relatively low seizure frequency, there was a significant reduction in seizure frequency during vigabatrin treatment. No significant treatment effect was found for the remaining 15 patients, who presented with mixed seizure types, multifocal electroencephalographic abnormalities, and high seizure frequencies. Tolerability to vigabatrin was good; the most frequently reported unwanted effect was drowsiness. Plasma concentrations of phenytoin showed a significant reduction during the vigabatrin period. The results demonstrate the efficacy and good tolerability of vigabatrin therapy in patients with severe complex partial epilepsy. PMID- 2887155 TI - Hypnotics. PMID- 2887153 TI - Effects of ALO 2145 on intraocular pressure following argon laser trabeculoplasty. AB - A prospective, randomized, double-masked study compared topical 1% ALO 2145, an alpha 2-agonist, with placebo in therapy for immediate postoperative intraocular pressure (IOP) rise after argon laser trabeculoplasty. Seventy-three eyes (73 patients) underwent 360 degrees of treatment utilizing 80 spots of 800 to 1000 mW of power. Intraocular pressure rise was measured hourly for the first three hours after operation, at one week, and at one month. Eyes treated with ALO 2145 had both significantly lower mean IOPs and greater IOP decreases from baseline than placebo-treated eyes during the first three hours after operation. No eyes treated with ALO 2145 and six eyes (18%) treated with placebo experienced an IOP rise of 10 mm Hg or greater. Twenty eyes (59%) in the placebo group and eight eyes (21%) treated with ALO 2145 had an IOP elevation. No change was detected in the mean heart rate. ALO 2145 appears to be effective in eliminating large, acute IOP elevations after argon laser trabeculoplasty. PMID- 2887156 TI - Takayasu's disease. PMID- 2887157 TI - Aminophylline in acute asthma. AB - It is widely believed that theophylline is a valuable addition to beta-agonists in the treatment of asthma. This is true when beta-agonists are given in low doses, but available evidence suggests that theophylline adds little or nothing to the effect of maximal doses of beta-agonists. Clinical trials, albeit some with limitations, in acute asthma support the view that theophylline confers no benefit on patients treated with high-dose beta-agonists. As theophylline is a difficult drug to use safely, and its toxicity is serious, its use should be confined to unusual circumstances, and the dose should be small. PMID- 2887158 TI - The use of the right gastro-epiploic artery in coronary artery bypass grafting. AB - Thirty consecutive patients with angina pectoris undergoing coronary artery bypass grafting using the proximally attached right gastro-epiploic artery are described. Posterior coronary arteries were grafted using the right gastro epiploic artery, and grafts to the left coronary artery were done using predominantly internal mammary artery grafts. The right gastro-epiploic artery graft is mobilized along the greater curvature of the stomach, and transected distally. With cardiopulmonary bypass and blood cardioplegic arrest for myocardial preservation during cross-clamping of the aorta, the distal end of the artery is anastomosed end-to-side to the posterior descending artery or a postero lateral branch, or to both, using a sequential technique. Twenty-five of the patients complained of symptoms suggestive of angina early postoperatively but are currently symptom-free with normal exercise tolerance. Thirteen patients had postoperative exercise tests: eight were normal, two were inconclusive, and three were abnormal. Nine grafted coronary arteries were re-angiogrammed, and seven were judged to be patent. It is concluded that, as an alternative resource, the right gastro-epiploic artery can be used to bypass coronary obstructions expeditiously and with results comparable to those obtained with the saphenous vein or internal mammary artery. PMID- 2887159 TI - Pili of Bordetella avium: expression, characterization, and role in in vitro adherence. AB - Electron microscopy revealed pili on all isolates of Bordetella avium and B. avium-like bacteria examined. Trypticase soy broth (TSB) and 2% peptone agar were the best media for promoting pilus expression. Cultures grown at 37 or 42 C had similar pilus production, whereas cultures grown at 18 C produced few or no pili. Pilus expression of the Art Vax strain was best when that strain was grown in TSB, but the strain yielded fewer pili than B. avium and B. avium-like isolates grown under the same cultural conditions. B. avium pili had a diameter of 2.0 nm, ranged in length from 370 nm to 1500 nm, and had a protein subunit molecular mass of about 13,100 daltons. Purified pili from B. avium did not hemagglutinate guinea pig erythrocytes, and a 1:20 dilution of hyperimmune antisera against B. avium pili did not block the hemagglutinating activity of whole-cell preparations of B. avium. In the indirect immunofluorescence test, B. avium isolates and the Art Vax strain adhered to the tracheal explants of turkeys, but B. avium-like isolates did not. Purified pili from B. avium adhered to the surface of the mucosal lining of the tracheal explants, and hyperimmune antisera against B. avium pili blocked the in vitro adherence of whole-cell preparations of B. avium. It was concluded that pili of B. avium are involved in the in vitro attachment of that bacterium to the mucosal surface of turkey tracheal explants. PMID- 2887161 TI - The potentiating effects of phorbol ester on ACTH-, cholera toxin-, and forskolin induced cAMP production by cultured bovine adrenal cells is not mediated by the inactivation of alpha subunit of Gi protein. AB - Phorbol ester (PMA) potentiates ACTH-induced cAMP production by both fresh isolated and 7-day-old cultured adrenal cells, but the effect on cultured cells was greater than in fresh cells. In cultured cells the potentiating effects of PMA were dose-dependent and were observed at each effective dose of ACTH without modification of the ED50 for this hormone. These effects of PMA do not seem to be exerted through a modification of the alpha subunit of Gi since pretreatment of the cells with Bordetella pertussis toxin did not modify the action of PMA and since the amount of alpha i in 7-day-old cultured cells was ten times lower than in fresh cells, while the potentiating effect was lower in the latter. Moreover, since PMA still exerted its potentiating action in cells stimulated by maximal concentration of cholera toxin or forskolin either alone or in combination with ACTH, it is likely that its action is not mediated exclusively by the alpha subunit of Gs. Taken together, the present results and those of the literature suggest that this potentiating effect of phorbol ester on effector-induced cAMP production might be mediated by inhibition of the beta-subunit of G proteins. PMID- 2887160 TI - The aryl hydrocarbon hydroxylase (Ah) locus and a novel restriction-fragment length polymorphism (RFLP) are located on mouse chromosome 12. AB - The aryl hydrocarbon hydroxylase (Ah) locus that controls the induction of chemical carcinogen-metabolizing enzymes in mice has been found to be linked to a new restriction-fragment length polymorphism (RFLP). Only C57BL/6 and closely related inbred strains displayed a 7.6-kb HindIII restriction fragment, while all other inbred strains tested displayed an 11.2-kb HindIII restriction fragment when using plasmid pRC2.3 as the hybridization probe. Polymorphisms in this region can also be detected with two other restriction enzymes: SacI and EcoRV. Linkage of Ah and the restriction-fragment length polymorphism was first detected using the BXD (C57BL/6 x DBA/2) recombinant inbred strains and was confirmed by a backcross. Both the restriction-fragment length polymorphism and Ah were not linked to the standard genetic markers Hba, Hbb, b, d, C-3, and W. However, comparison of the RFLP strain distribution pattern in the BXD recombinant inbred set with the strain distribution pattern of another RFLP, known to be located on chromosome 12, shows complete concordance in 24 of 24 strains, thereby locating Ah on chromosome 12. PMID- 2887162 TI - Activation of tyrosine hydroxylase by micromolar concentrations of calcium in digitonin-permeabilized adrenal medullary cells. AB - In digitonin-permeabilized bovine adrenal medullary cells, Ca2+ (0.1-1.0 microM) caused an activation of tyrosine hydroxylase which was dependent on the presence of ATP. This Ca2+-induced activation of the enzyme was observed even in the presence of optimal concentration of either cyclic AMP or 12-O tetradecanoylphorbol-13-acetate (TPA) which by itself increased the enzyme activity. Calmodulin inhibitors, trifluoperazine (TFP) and N-(6-aminohexyl)-5 chloro-1-naphtalenesulfonamide (W-7), had little effect on the Ca2+-evoked activation of enzyme. These results suggest that micromolar concentrations of Ca2+ activate the activity of tyrosine hydroxylase probably through a Ca2+ dependent phosphorylation in digitonin-permeabilized adrenal medullary cells although the protein kinase(s) responsible for it still remains to be determined. PMID- 2887163 TI - Inhibition by some phenolic antioxidants of Ca2+ uptake and neurotransmitter release from brain synaptosomes. AB - We present observations on the action of the phenolic antioxidants 2,3-tert-butyl 4-methoxyphenol (BHT); 2,6-di-tert-butyl-4-methylphenol (BHA); n-propyl-gallate and nordihydroguaiaretic acid (NDGA) on the function of guinea pig cerebral cortex synaptosomes. While the Ca2+ uptake observed under non depolarizing conditions is not affected by these agents, the depolarization induced Ca2+ uptake is strongly inhibited. Similarly the phenolic antioxidants studied inhibit the Ca2+ plus depolarization induced exocytosis of GABA and glutamate. These results which are similar to those previously obtained in blood platelets (Alexandre, A. et. al. Biochem. Biophys. Res. Comm. 139, 509-514, 1986), may indicate that free radical intermediates are involved in stimulus-secretion coupling. PMID- 2887165 TI - In vitro mutated beta subunits from the F1-ATPase of the thermophilic bacterium, PS3, containing glutamine in place of glutamic acid in positions 190 or 201 assembles with the alpha and gamma subunits to produce inactive complexes. AB - Using site-directed mutagenesis, Glu-190 or Glu-201 of the beta subunit of the F1 ATPase from the thermophilic bacterium PS3 were replaced with glutamine. It was possible to reconstitute complexes of the mutated beta subunits with alpha and gamma subunits, but the complexes did not have ATPase activity. It is concluded that carboxylic acid side chains of Glu-190 and Glu-201 of the beta subunit are essential for catalytic activity of F1-ATPase. PMID- 2887164 TI - Beta-adrenergic agonist- and prostaglandin-mediated regulation of cAMP levels in Ewing's sarcoma cells in culture. AB - This is the first report demonstrating hormonal control of cAMP levels in Ewing's sarcoma cells. Two classes of hormones, beta-adrenergic agonists and prostaglandins stimulate cAMP production in cultured Ewing's sarcoma cells. The efficacy order for beta-adrenergic agonists is (-)-isoprenaline greater than or equal to (-)-noradrenaline greater than or equal to (-)-adrenaline much greater than (-)-phenylephrine. The stimulatory effect of (-)-noradrenaline is antagonized by beta 1-selective metoprolol and also by beta 2-selective ICI 118,551. The efficacy order for prostaglandins (PG) is PGE1 greater than PGI2 greater than PGE2 much greater than PGF2 alpha; 6-keto PGF1 alpha and PGD2 do not influence cAMP levels in Ewing's sarcoma cells. Cultures pretreated with PGE2 are less responsive to a second challenge with PGE2 but their response to (-) isoprenaline is unimpaired. Similarly, pretreatment with (-)-isoprenaline induces homologous desensitization to (-)-isoprenaline and has no effect on the PGE2 stimulated increase in cAMP. We conclude that these cells provide an ideal model for the study of the initial steps of beta-adrenergic and prostaglandin action in Ewing's sarcoma. PMID- 2887166 TI - Modulated expression of human homeobox genes in differentiating intestinal cells. AB - Homeobox genes (Hox genes) control segmentation and segment specificity in Drosophila. Hox genes have been detected in several species from insects to vertebrates. Differential and stage-related expression has been observed in human embryonic tissues as well. We have investigated whether the cell line Caco-2 and human adult intestine express Hox genes. Caco-2 is a cell line derived from a human colon carcinoma and exhibits a spontaneous enterocytic differentiation after cellular confluency in vitro. At 7, 14 and 21 days after seeding we have found that Hox-2.3 and one Hox-3 gene hybridize to poly(A)+RNA in a stage-related fashion. Moreover, the 21 days pattern of hybridization resembles that one observed in adult small intestine. The Caco-2 cell line provides a model system that allows a detailed analysis of cellular factors controlling transcription and stability of Hox gene products. PMID- 2887167 TI - Effect of lysophosphatidylcholine on K+ transport in rat heavy gastric membranes enriched with (H+-K+)-ATPase. AB - K+- and ATP-dependent H+-accumulation in rat heavy gastric membrane vesicles enriched with (H+-K+)-ATPase was markedly stimulated by amphiphiles like lysophosphatidylcholine and Zwittergent 3-14 at concentrations of 10(-5) M. Their stimulatory effect was dependent on K+-concentration in the medium and was abolished by SCH 28,080, a specific inhibitor of (H+-K+)-ATPase. Lysophosphatidylcholine at the optimal dose (3 X 10(-5) M) showed dual effects on K+-dependent membrane functions; it stimulated the rate of K+-uptake by nearly 60%, but partially inhibited SCH 28,080-sensitive and K+-dependent ATP-hydrolysis (about 20% reduction). These data indicate that H+-pumping through (H+-K+)-ATPase in the inside-out gastric membrane vesicles was facilitated by the stimulatory effect of lysophosphatidylcholine on membrane K+-transport in spite of its partial inhibition of ATP-hydrolysis. It appears that the rate limiting step for operation of the ATPase is the availability of K+ ions in the luminal side of the pump. We propose that ionic amphiphiles may modulate K+-transport in rat heavy gastric membranes through specific interactions with the putative K+-transporter. PMID- 2887168 TI - Reversible conversion of tyrosine hydroxylase to an inactive form by antipain. AB - Tyrosine hydroxylase, the rate-limiting enzyme in the biosynthesis of catecholamines, was reversibly inactivated by incubation with antipain, which is known as a microbial protease inhibitor. The inactivation was a time-dependent reaction and it was prominent when the enzyme was assayed at a neutral pH but not when assayed at an acidic pH. The inactivated enzyme was markedly activated by cyclic AMP-dependent protein kinase. Other microbial protease inhibitors such as leupeptin, chymostatin, and pepstatin did not induce such as inactivation of the enzyme. PMID- 2887169 TI - Isolation of a novel cDNA clone for human tyrosine hydroxylase: alternative RNA splicing produces four kinds of mRNA from a single gene. AB - Human tyrosine hydroxylase (TH) cDNA was isolated by molecular cloning. Lambda gt 11 cDNA library constructed from human pheochromocytoma was screened with a synthetic 23-mer oligonucleotide complementary to rat TH mRNA. We found a novel type of cDNA clone whose N-terminal sequence is similar to but clearly distinct from each of the three types (type 1, 2 and 3) of TH cDNA reported by Grima et al. [Nature (1987) 326, 707-711]. It contains both the 12-bp insert characteristic of type 2 cDNA and the 81-bp sequence of type 3. This novel cDNA clone was designated as type 4. Southern blot analysis of human genomic DNA indicated that TH is encoded by a single gene. This suggests that the four different forms of TH mRNA are produced by alternative RNA splicing from a single primary transcript. PMID- 2887170 TI - Experimental approach of treatment of cerebral ischemia by a combination of raubasine and almitrine. AB - Post-oligemic syndrome in rat results from transient reduction of cerebral blood flow obtained by bilateral carotid ligation for 60 min and mild systemic hypotension induced by s.c. injection of sodium nitroprusside. Over an acute phase of 3 days the syndrome consisted in a marked neurological deficit evidenced by a decrease in scores obtained by rats in "visual placing" test, a loss in learning ability substantiated by a decrease in the ability of rats to integrate and remember a passive avoidance reflex; biochemical disorders revealed by an increase in cerebral water, calcium and free fatty acids (FFA) contents associated with a decrease in cerebral potassium content. From 2 weeks until 4 weeks after ischemic insult a process of malacia of the cerebral tissue occurred. Treatment of rats with a combination of raubasine and almitrine (5023 SE, Duxil) by oral route (16.7 to 66.6 mg kg-1) twice daily from 1 h post-oligemia to sacrifice, in the acute phase, led to 1. an improvement of visual placing response, 2. an increase in learning ability, 3. a decrease in water and calcium cerebral contents associated with an increase in potassium cerebral contents. Enhancement of FFA contents was reduced when preventive treatment was associated with curative treatment. Incidence and extent of encephalomalacia was reduced by the drug in the chronic phase. It is concluded that in a rat model of post oligemic syndrome and under these experimental conditions 5023 SE caused, 3 days after the ischemic insult, a significant reduction of cerebral disorders that may explain the therapeutic effect of the drug evidenced 4 weeks later. PMID- 2887171 TI - Spasmolytic action of the cerebral circulation improver 6,7-dimethoxy-1- (3,4 dimethoxybenzyl)-4-[( 4-(2-methoxyphenyl)-1-piperazinyl]methyl) isoquinoline in isolated canine vessels. AB - Vasodilating action of a new calmodulin antagonist, 6,7-dimethoxy-1-(3,4 dimethoxybenzyl)-4-[( 4-(2- methoxyphenyl)-1-piperazinyl] methyl) isoquinoline (Ro 22-4849) was examined in various isolated canine vessels. Ro 22-4839 was found to dilate basilar and middle cerebral arteries and to non-selectively antagonize submaximal contraction of these arteries under the treatment of various constrictors (K+, Ca2+, PGF2 alpha (dinoprost), serotonin and incubated blood) with IC50 values ranging from 0.043 to 1.69 mumol/l. Vasospasmolytic action of the compound in these cerebral arteries was 9 and 20 times greater than those in coronary and femoral arteries, respectively. The arterial relaxation by Ro 22-4839 was hardly overcome by addition of extra calcium and Ro 22-4839 did not alter calcium channels in the guinea-pig papillary muscle, although the compound inhibited the tension development, confirming its calmodulin antagonistic properties. Ro 22-4839 inhibited norepinephrine (NE)-induced contraction of femoral arterial strips concentration-dependently, and prevented NE-induced lethal extravasation in mice with an ED50 value of 1.96 mg/kg p.o. In in vitro [3H]-dihydroergocryptine binding assay and ex vivo [3H]-WB-4101 (2 [(2',6'-dimethoxy)phenoxyethylamino] methylbenzodioxan) binding assay, the compound showed a potent inhibitory action on alpha 1-adrenoceptor. These findings indicate that Ro 22-4839 exerts the spasmolytic effects on cerebral vessels through calmodulin antagonistic properties combined with alpha 1 adrenoceptor blocking action. PMID- 2887172 TI - Octanol/buffer partition coefficients of different betablockers. AB - In own measurements octanol/buffer pH 7.4 partition coefficients of 10 different betablockers were determined and the clinical relevance of these data is discussed by using reference data. PMID- 2887173 TI - Pharmacodynamics of the new H1-antagonist 3-amino-9,13b-dihydro-1H dibenz[c,f]imidazo[1,5-a]azepine hydrochloride in volunteers. AB - The inhibitory effects of 3-amino-9,13b-dihydro-1H-dibenz[1,5-a]azepine hydrochloride (WAL 801 CL), a new H1-receptor antagonist, on histamine-induced skin wheals were studied in 9 volunteers. The study was a double-blind, randomized (Latin square) change-over, intraindividual comparison of the effects of single doses of 2,6 and 18 mg WAL 801 CL and of placebo and 2 mg ketotifen on skin wheals induced by intradermal injections of 5 micrograms hystamine 1, 2, 4, 6 and 8 h after administration of the drugs. The injection of 5 micrograms was also made prior to each drug administration. The effects on psychological performance and the subjective state were also evaluated. The following tests were employed: simple visual reaction time (RT), critical flicker fusion frequency (C3F) and von Zerssen's self-rating scale Bf-S, assessing state of mood. There was a washout period of at least 72 h between each course of treatment. A decrease in the size of the histamine wheal was observed 1 h after WAL 801 CL and was maintained for at least 8 h. The reduction in the size of the histamine wheal was between 44% (2.0 mg) and 71% (18.0 mg). After ketotifen a marked decrease in the wheal area was observed between 4 and 8 h after administration of the drug, with maximum histamine antagonism of 59% after 6 h. The inhibitory effects of 6 and 18 mg WAL 801 CL and 2 mg ketotifen were statistically significant compared with placebo. 8 of 9 subjects felt tired (subjective report) after ketotifen, corresponding changes could be detected by Zerssen's state of mood scale Bf-S, but not by other psychological performance measures (RT, C3F).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887175 TI - Alprazolam dependence in mice. AB - Mice were treated with 0.025% alprazolam incorporated into their laboratory chow for periods of one, two, and four weeks. Treated animals gained weight and appeared healthy during treatment, although an increased number of animals were lost in the treatment groups due to cannibalism. When regular food was substituted, alprazolam-treated animals experienced a withdrawal reaction qualitatively similar to that previously observed following similar lengths of treatment with 0.1% diazepam in food. The withdrawal reaction following alprazolam had a faster onset and a shorter time course, and was less intense. In a separate experiment, eight mice were treated with alprazolam for two weeks but were housed singly. This eliminated the cannibalism problem and no animals were lost during the treatment phase; the withdrawal syndrome was similar to that seen in group-housed animals. The model of benzodiazepine dependence in mice would appear to generalize to the entire class of drugs and may permit distinctions to be made between the time-course of withdrawal reactions between the various members of that class. PMID- 2887174 TI - Concentrations of carbohydrate-deficient transferrin in dialysed plasma from drunken drivers. AB - Serum carbohydrate-deficient transferrin (CDT) has previously been found to be a sensitive and specific biological marker of excessive alcohol consumption. In order to study the prevalence of excessive drinking among arrested drunken drivers, CDT was measured in plasma samples from 50 drunken drivers after dialysis against 0.9% NaCl. 60% of the drivers had elevated CDT. When data on CDT from other studies were used to interpret our CDT results, it was estimated that at least 60% of the drunken drivers were consuming at least 50 g pure alcohol per day. Drunken drivers involved in road traffic accidents tended to have higher CDT values than other drunken drivers, indicating a higher alcohol consumption, while drivers below 30 years of age had lower CDT values than older ones. PMID- 2887176 TI - Psychotherapeutic drugs. Implications in occupational health nursing. PMID- 2887177 TI - Increase in [3H]glutamate release from slices of dentate gyrus and hippocampus following classical conditioning in the rat. AB - The release of amino acids was examined in three hippocampal areas following classical conditioning. Paired or unpaired tone(CS)-shock(US) presentations were given to animals engaged in a previously acquired food-motivated lever-pressing task. Conditioned suppression of lever-pressing was the behavioural measure of conditioning. The dentate gyrus and areas CA1 and CA3 of the hippocampus were removed bilaterally from conditioned and pseudoconditioned animals, and slices cut and stored in liquid nitrogen for subsequent in vitro analysis of the release of radiolabelled glutamate and aspartate. K+-stimulated release of radiolabelled amino acids was analysed in the presence and absence of extracellular Ca2+. Potassium-stimulated, Ca2+-dependent release of [3H]glutamate was significantly greater in slices of dentate gyrus and area CA1 prepared from conditioned animals than from pseudoconditioned animals. This finding identifies a neurochemical change associated with classical conditioning which is similar to the increase in transmitter release seen in hippocampal long-term potentiation (LTP), and which is consistent with the hypothesis that an LTP-like mechanism is involved in mnemonic processes. PMID- 2887178 TI - Disturbances in histidine metabolism in children with speech abnormalities. AB - Catabolism of histidine was investigated in 24 patients with different speech and language disorders and with significantly low histidase activity in stratum corneum. No classical histidinemia was found. Biochemical investigation of these patients after loading with L-histidine led to the conclusions that low histidase activity in stratum corneum was connected with: disturbances in folic acid metabolism (2 cases); "atypical histidinemia" (1 case); heterozygotes of histidinemia (2 cases); normal liver histidine metabolism but abnormal in other tissues (18 cases); previously unknown error of histidine metabolism (1 case). PMID- 2887179 TI - Mapping the human genes. AB - The article recalls achievements in the area of human gene mapping and covers recent developments in somatic cell hybridization studies and recombinant DNA technology. PMID- 2887180 TI - N-terminal fibronectin 30-kDa fragment mediates the immobilization of soluble fibrin by factor XIIIa-coated polystyrene beads. AB - Polystyrene beads coated with thrombin-activated Factor XIII (plasma transglutaminase, plasma transamidase) retained soluble 125I-fibrin, if a 30-kDa fragment of fibronectin was present. The fragment was obtained by proteolytic cleavage of plasma fibronectin with trypsin, but was also available with plasmin or thrombin. It represented a fibrin-binding domain at the N-terminus of each of the two subunit chains and contained close to its amino end a transamidase reactive site. Fibronectin was unable to mediate the binding of 125I-fibrin to Factor XIIIa-coated beads. 125I-fibrinogen was hardly recognized by the beads even in presence of the fibronectin fragment. The relatively slow binding of 125I fibrin was inhibited by 0.15 mM putrescine or by a pretreatment of the coated beads with EDTA or N-ethylmaleinimide indicating the involvement of a transamidation in the binding reaction. Immobilization of 125I-fibrin in presence of the fibronectin fragment is assumed to require a covalent cross-linking of the two ligands at the immobilized transamidase giving rise to a product which is retained strongly. The possibility is discussed that a surface-attached transamidase might act as a fibrin receptor which requires the fibronectin fragment as a cofactor. PMID- 2887182 TI - Perinatal hypoxia and hepatic cell function in preterm and full term newborn infants. AB - Gamma-glutamyl transpeptidase activity and the serum concentration of lipoprotein x, indirect bilirubin and total bile acids were measured in 28 preterm and 24 full term newborn infants, with or without hypoxia, at the postnatal age 3-4 days. Those preterm and full term babies who suffered from hypoxia had increased mean lipoprotein-x, bilirubin, total bile acid concentration and gamma-glutamyl transpeptidase activity in comparison to that of controls, but the differences were not significant statistically. Clinical implications of the results are briefly discussed. PMID- 2887181 TI - Betaxolol eye drops as a safe medication to lower intraocular pressure. AB - Betaxolol, a cardioselective beta 1-adrenergic antagonist, was used in a clinical trial in nine patients with glaucoma and chronic obstructive airways disease to assess its patient acceptance, and its effect on intraocular pressure, respiratory function, corneal and tear function. Betaxolol was well tolerated by all patients with no adverse symptoms. It significantly lowered intraocular pressure (p = 0.03) with no significant change in respiratory function (forced expiratory volume in one second (FEV1), mean mid expiratory flow rate (MMEFR) and vital capacity). Although there was a tendency to decreased wetting with Schirmer 1, decreased break-up time and increased corneal staining with Rose Bengal, this was not statistically significant in this small series. We confirmed the previously reported efficacy and safety of betaxolol in patients with glaucoma and airways disease with satisfactory patient acceptance. PMID- 2887183 TI - HTLV-I infection of cerebrospinal fluid T cells from patients with chronic neurologic disease. AB - Antibodies reacting with HTLV-I, the etiologic agent of acute T cell leukemia/lymphoma and a transforming agent for T4-positive lymphocytes in vitro, have recently been described in sera of patients with chronic neurologic disease in the absence of lymphoproliferative disorders. The largest number of such cases was described in Japan and in the Caribbean and parts of South America. We report here two cases of patients with chronic neurologic disease whose cerebrospinal fluid (CSF)-derived T cells contain HTLV-I specific RNA sequences and antigens and are expressing retroviral particles. Only one of these patients has demonstrable antibody to HTLV-I in serum or CSF. PMID- 2887184 TI - Successful use of a right ventricular assist device. AB - Right ventricular failure caused by myocardial infarction may be refractory to treatment designed to support the systemic ventricle. A new type of right ventricular assist device driven by an impeller pump was successfully used for 79 hours after emergency revascularisation after right coronary occlusion. Despite renal failure requiring haemofiltration the patient has now fully recovered. PMID- 2887185 TI - Pharmacokinetics of isoxicam in hepatic disease. AB - 1 The pharmacokinetics of single and repeated oral doses of isoxicam, an extensively metabolized drug, were studied in patients with compensated and decompensated hepatic disease. 2 After a single oral dose, isoxicam was slowly absorbed and eliminated (half-life ranging from 10.5 to 53.9 h). Its pharmacokinetics did not differ from those observed in healthy volunteers and were not significantly influenced by the severity of hepatic disease. However, the t1/2 of isoxicam was found to be inversely (r = -0.700, P less than 0.05 n = 14) related to the log gamma-glutamyl transpeptidase plasma activity. 3 During chronic oral treatment in patients with compensated hepatic insufficiency, steady state was achieved after 7-9 days of therapy. The mean elimination half-life of isoxicam in five patients was 42.6 +/- 4.5 h, a value which was not statistically different from that obtained in the single dose study. 4 It was concluded that patients with hepatic insufficiency do not require a systematic modification of drug dosage but that long-term treatment should be employed with caution in these patients. PMID- 2887186 TI - Responses to mental stress and physical provocations before and during long term treatment of hypertensive patients with beta-adrenoceptor blockers or hydrochlorothiazide. AB - 1 Cardiovascular and sympatho-adrenal responsiveness to mental stress (CWT; a colour word test), orthostatic testing (ORT) and a cold pressor test (CPT) were examined in three groups of hypertensive patients (n = 14-16) before and after 6 months treatment with metoprolol (243 +/- 26 mg daily), propranolol (149 +/- 16 mg daily) or hydrochlorothiazide (50 +/- 8 mg daily) in an open trial design. 2 Treatment reduced outpatient blood pressures in the three groups similarly (from approximately 155/102 to 135/90 mm Hg). During treatment resting blood pressures in the laboratory were clearly reduced by beta-adrenoceptor blockade but not by thiazide treatment. Metoprolol and propranolol caused similar reductions of basal heart rates and plasma glycerol levels, whereas only propranolol reduced cyclic AMP concentrations in plasma. 3 Before treatment CWT and CPT increased systolic and diastolic blood pressures by about 30%. Heart rate increased by about 30 beats min-1 during CWT and 10-15 beats min-1 during CPT and ORT. Small venous plasma adrenaline responses were evoked by all tests, whereas noradrenaline was elevated mainly by CPT and ORT. Dopamine levels did not change. 4 Heart rate responses to all stressors were markedly and similarly reduced, whereas blood pressure responses were essentially unchanged during metoprolol or propranolol treatment. In the thiazide group circulatory responses to CWT were slightly attenuated, whereas responses to ORT and CPT were unchanged. 5 The systolic blood pressure levels were reduced throughout the test session in all three groups, although less so in the hydrochlorothiazide group. Both beta-adrenoceptor antagonists clearly reduced diastolic blood pressure and heart rate levels at rest and during stress, whereas thiazide treatment caused no significant changes in these respects. 6 The rate pressure product, which increased by 80-100% in response to CWT before treatment, was more markedly reduced by beta-adrenoceptor blockade than by thiazide treatment both at rest and during stress. 7 Self ratings (visual analogue scales) of stress and irritation were increased by CWT in a similar fashion before and during treatment in all groups. beta-adrenoceptor blockade was associated with higher subjective ratings of tiredness at rest, but not after CWT. Performance in the CWT increased slightly more in the thiazide group. The physiological responses to CWT were not correlated to the subjective responses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2887187 TI - Bronchodilator action of the anti-histaminic terfenadine. PMID- 2887188 TI - Assessment of a new hypnotic imidazo-pyridine (zolpidem) as oral premedication. AB - 1 A new imidazo-pyridine hypnotic (zolpidem 10 mg and 20 mg) was compared with placebo as premedication before general anaesthesia in female patients undergoing minor gynaecological surgery. Efficacy and tolerance before and after anaesthesia were assessed. Psychomotor testing was used to study recovery from anaesthesia. 2 Both doses of zolpidem produced good sedation pre-operatively but only the higher dose was associated with anterograde amnesia. 3 Premorbid anxiety scores were low in the group of patients studied and were unaffected by either dose of zolpidem. 4 There were no significant effects on the course of anaesthesia. However, postoperatively there was a tendency for wake-up to be delayed in those patients who received either dose of zolpidem. 5 Postoperative recovery, as indicated by tests of psychomotor performance, was noticeably delayed with a dose of 20 mg compared with placebo whilst psychomotor performance had returned towards baseline levels 3 h after wake-up in those patients who had received placebo. The zolpidem 10 mg group was intermediate. 6 Zolpidem may be a suitable premedicant when hypnosis and amnesia only are required. PMID- 2887189 TI - Post-exercise hypotension: the effects of epanolol or atenolol on some hormonal and cardiovascular variables in hypertensive men. AB - 1 Eight men with primary hypertension were treated for 3 weeks with placebo, epanolol (200 mg or 400 mg), or atenolol 100 mg in a randomised cross-over study. Each active treatment period was preceded by a 3 week placebo treatment period and both investigators and subjects were blind to the active drug sequence. 2 At the end of each period, measurements were made of resting cardiovascular (heart rate, blood pressure, forearm blood flow) and biochemical variables (plasma renin, angiotensin II, aldosterone, adrenaline, noradrenaline, vasopressin, sodium and potassium concentrations and osmolality). Responses to exercise (including gas exchange, sweat rate, and ratings of perceived exertion) and the reflex cardiovascular adjustments to distal body subatmospheric pressure were also assessed. 3 The reduction of exercise-induced tachycardia by epanolol 400 mg was comparable to that of atenolol. There was very little difference in the effects of atenolol or epanolol 400 mg on resting blood pressure, but in both cases blood pressures were usually significantly lower than with epanolol 200 mg. 4 Although each active treatment influenced the renin-angiotensin system and circulating levels of catecholamines, the exercise-induced reduction in blood pressure was unaffected. Thus, the hypotensive effects of pharmacological and non pharmacological interventions were additive. PMID- 2887191 TI - The effects of beta-adrenoceptor blockade on breathing during progressive exercise in normal man. AB - 1 We have studied the effects of single oral doses of 80 mg propranolol and 100 mg atenolol on breathing during progressive exercise in nine healthy men in a double-blind, placebo-controlled experiment. As judged by their effects on exercise heart rate significant levels of beta-adrenoceptor blockade were achieved. 2 At the two lower levels of work rate (50 watts and 100 watts) minute ventilation on atenolol was lower than on placebo while at the highest level of work (200 watts) minute ventilation was higher on atenolol than on placebo. The regression of VE atenolol on VE placebo was 1.28 which is significantly different from unity (P less than 0.001). The results with propranolol were more scattered and failed to reach the 5% level of significance. 3 Effects on the pattern of breathing are small but when minute ventilation is matched with placebo, atenolol results in larger tidal volumes and prolonged inspiratory and expiratory time. 4 These observations are discussed in relation to other work in the literature. PMID- 2887192 TI - Exercise-induced hyperkalaemia: effects of beta-adrenoceptor blocker vs diuretic. AB - Four groups of eight normotensive male volunteers performed a 60 min bicycle exercise test before and after 2 weeks of either placebo, hydrochlorothiazide (HCTZ, 25 mg day-1), pindolol (PIND, 10 mg day-1) or both drugs in combination using a double-blind, randomized design. During exercise on placebo serum potassium increased by 0.8 mmol l-1. HCTZ significantly decreased potassium levels at rest and during exercise by 0.2 mmol l-1. PIND did not affect resting potassium levels but potentiated the increase by 0.4 mmol l-1 at the end of exercise, and delayed the return to normal of serum potassium after exercise. The addition of HCTZ to PIND offset the potentiating effect of PIND on exercise induced hyperkalaemia (only after prolonged exercise) and accelerated the return to baseline after exercise. The results indicate that the hypokalaemic effect of HCTZ can oppose the hyperkalaemic effect of PIND during prolonged physical exercise and particularly during recovery. PMID- 2887190 TI - Haemodynamic effects of atenolol, labetalol, pindolol and captopril: a comparison in hypertensive patients with special reference to changes in limb blood flow, heart rate and left ventricular function. AB - 1 To compare the haemodynamic effects of secondary characteristics of beta adrenoceptor blockers with an angiotensin converting enzyme inhibitor forty patients with previously untreated mild to moderate hypertension were prescribed either atenolol 50-100 mg day-1, labetalol 200-800 mg day-1, pindolol 10-30 mg day-1 or captopril 25-100 mg day-1 and observed for 6 months. 2 Over this period: (a) All four drugs produced similar reductions in blood pressure at rest (P less than or equal to 0.01) and after exercise (P less than or equal to 0.01). (b) All four drugs significantly decreased resting forearm (P less than or equal to 0.01) and calf blood flow (P less than or equal to 0.01). They all also caused a significant reduction in the increased calf blood flow following exercise (P less than or equal to 0.01). (c) No drug produced a change in resting forearm vascular resistance, while resting calf vascular resistance was decreased by captopril and pindolol, unaltered by labetalol and increased by atenolol. Post-exercise calf vascular resistance was increased by atenolol, labetalol and pindolol but unaltered by captopril. (d) Although all four drugs produced a fall in resting heart rate this was significantly greater for atenolol and labetalol (P less than or equal to 0.01). All four treatments however significantly reduced the increase in heart rate following exercise (P less than or equal to 0.01). (e) No drug produced any significant change in resting and post-exercise stroke volume/ejection fraction. 3 It is concluded that despite differing modes of action all four drugs reduce limb blood flow. This primarily appears to be a consequence of reduced perfusion pressure associated with limited autoregulation of skeletal muscle circulation. The reduction in arterial vascular resistance produced by captopril and pindolol is inconsistent and does not appear of major benefit in preserving limb blood flow. The reduction in perfusion with the agents studied may in part be related to a fall in cardiac output associated with decreased heart rate. This suggests that captopril may exert antisympathetic activity when used as an antihypertensive agent. PMID- 2887193 TI - A system for transformation of rat liver cells in vitro by acute treatment with aflatoxin. AB - Aflatoxin B1 (AFB1) induced rat liver cancer is a well studied system of hepatocarcinogenesis. AFB1 has also been used to transform cultured rat liver derived cells in vitro. Cells in culture often have a reduced capacity to metabolise the AFB1 to its active metabolite, and often prolonged periods of exposure to the toxin have to be employed, with a long latency in the appearance of transformed cells in culture. We report here the transformation of a rat liver derived cell line by acute treatment with AFB1. An extrinsic metabolising system of quail microsomes, which convert AFB1 to its epoxide form with high efficiency, was used to activate the AFB1. A dose dependent cytotoxicity was obtained and neoplastic transformation was seen in the higher doses used. The enzyme GGT which has strong association with liver cell transformation both in vivo and in vitro was also elevated in the treated cells. PMID- 2887195 TI - Effect of an oral H1-receptor antagonist, terfenadine, on antigen-induced asthma. AB - We have investigated the effect of a specific H1-receptor antagonist, terfenadine, on antigen-induced asthma. In a double-blind, randomized fashion, nine stable asthmatics were given placebo, or terfenadine 60, 120 or 180 mg orally, 12 and 4 hours before challenge. Cumulative bronchial challenge with specific antigen aerosols were delivered from a nebulizer attached to a breath actuated dosimeter. Response was monitored by specific airway conductance and measurements from partial expiratory flow-volume curves, performed in a body plethysmograph, on line to a computer. Initially the histamine dose-response curves of four subjects were found to be shifted 10-fold to the right by terfenadine 60 mg, given orally. Compared with placebo, terfenadine 60 mg, given orally. Compared with placebo, terfenadine significantly shifted the mean antigen dose-response curves of all measurements to the right. However, this shift was small and not correlated to the dose of terfenadine. There was marked intersubject variation in the effect. Terfenadine produced no side effects. The immediate bronchial response to antigen can be attenuated by an oral H1-receptor antagonist, but the effect is small and, in general, unlikely to be clinically useful. PMID- 2887196 TI - Peripheral blood stem cell autografting: a new therapeutic option for AML? PMID- 2887194 TI - Ha-ras-1 restriction fragment length polymorphism and susceptibility to colon adenocarcinoma. AB - It is not yet clear whether some polymorphic variants of the Ha-ras-1 gene confer genetic predisposition to cancer. However, recent data on myelodysplasia and lung cancer are controversial. To clarify this point, 62 colorectal adenocarcinoma patients were examined for the Ha-ras-1 gene restriction fragment length polymorphism and results were compared with those of 108 healthy blood donors. No Ha-ras-1 polymorphic variants specifically associated with the cancer patients were detected. However, a specific genotype was significantly more frequent in the healthy donors than in the cancer patients (16% versus 5%), suggesting an interaction between the two alleles of the gene. PMID- 2887197 TI - A follow-up study of patients treated for benzodiazepine dependence. AB - By interviewing and administering questionnaires to 63 patients one to five years after treatment for benzodiazepine dependence the long-term success rate was examined together with factors associated with outcome. Fifty-four per cent of patients had permanently withdrawn from medication at follow-up. Most of those who were successful continued to experience psychiatric symptoms after discharge. Significantly more women than men managed to withdraw from medication. Outcome was not related to previous benzodiazepine regimen, psychiatric history or experiences of withdrawal. It is argued that psychological adjuncts should be included in the treatment of benzodiazepine dependence in order to prevent relapse. PMID- 2887198 TI - Replacement of potassium chloride by potassium glutamate dramatically enhances protein-DNA interactions in vitro. AB - Although protein-nucleic acid interactions exhibit dramatic dependences on both ion concentration and type in vitro, large variations in intracellular ion concentrations can occur in Escherichia coli and other organisms without apparent effects on gene expression in vivo. E. coli accumulates K+ and glutamate as cytoplasmic osmolytes. The cytoplasmic K+ concentration in E. coli varies from less than 0.2 to greater than 0.9 m as a function of external osmolarity; corresponding cytoplasmic glutamate concentrations range from less than 0.03 to greater than 0.25 m. Only low levels of chloride occur in the cytoplasm of E. coli at all osmotic conditions. Since most in vitro studies have been performed in chloride salts, whereas glutamate is the more relevant physiological anion, we have measured the effects of the substitution of potassium glutamate (KGlu) for KCl on the kinetics and equilibria of a variety of site-specific protein-DNA interactions in vitro. Both the interaction of E. coli RNA polymerase with two phage lambda promoters and the interactions of various restriction enzymes with their DNA cleavage sites are enhanced by this substitution. Using the abortive initiation assay, we find a greater than 30-fold increase in the second-order rate constant for open complex formation at the lambda PR promoter and a 10-fold increase at the lambda PR' promoter, when KGlu is substituted for KCl. Replacement of KCl by KGlu does not affect the strong salt dependences of these interactions; increasing either KCl or KGlu concentrations decreases both reaction rates and extents. Substitution of glutamate for chloride does, however, shift the range of salt concentrations over which these interactions are observable to higher K+ concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887200 TI - Interactions between nucleotide binding sites on chloroplast coupling factor during ATP hydrolysis. AB - The initial hydrolysis of CaATP by chloroplast coupling factor 1 was studied with the quenched-flow method. The time course of hydrolysis can be described as a first-order conversion of the enzyme to an active form followed by steady-state formation of product. The rat constant for the first-order process is independent of substrate concentration but increases hyperbolically to a limiting value of 0.43 s-1 with increasing concentrations of free Ca2+. A mechanism involving a Ca2+-triggered conversion to an active form of the enzyme is consistent with the data. The steady-state rate varied sigmoidally with the CaATP concentration. Initial exchange of tightly bound ADP is complex: approximately 50% of the bound nucleotide is lost within 30 s, with complete exchange requiring several minutes. The first-order rate constant characterizing the rapid phase of the reaction increases hyperbolically to a limiting value of 0.26 s-1 as the concentration of CaATP is increased, indicating that the binding of CaATP to the enzyme promotes the exchange process. Modification of the quenched-flow apparatus permitted measurement of the rate of nucleotide exchange during steady-state catalysis. The value of the first-order rate constant characterizing this process is similar to the catalytic rate constant determined under identical conditions. When MgATP is tightly bound to the enzyme, none of the kinetic properties of the enzyme described above were significantly changed. The results obtained suggest a mechanism in which two sites on the enzyme participate in catalysis. Several possible mechanisms consistent with the data are discussed. PMID- 2887199 TI - Hydrodynamic properties of the chromaffin granule hydrogen ion pumping adenosinetriphosphatase. AB - We have determined the hydrodynamic properties of detergent-solubilized ATPase, which is coupled to H+ pumping in bovine adrenal chromaffin granules, by sedimentation equilibrium centrifugation and gel permeation chromatography. The protein solubilized with detergent containing phosphatidylserine sediments as a particle of 264,000 daltons and partial specific volume 0.829 cm3/g. Assuming a protein v of 0.73 and using the v measured for detergent and lipid mixed micelles of 0.93 cm3/g, we calculated that the protein component has a mass of 134,000 daltons and that the equivalent of approximately 1.5 micelles of detergent are bound per particle. The particle exhibits a Stokes radius of 43 A, which, together with the calculated particle volume, indicates an axial ratio close to 1. We conclude that the ATPase is an intrinsic membrane protein with a structure very different from that of mitochondrial F1F0 ATPase. PMID- 2887201 TI - Tumor-promoting phorbol ester amplifies the inductions of tyrosine aminotransferase and ornithine decarboxylase by glucocorticoid. AB - In adrenalectomized rats, the tumor-promoting phorbol ester 12-O tetradecanoylphorbol 13-acetate (TPA) markedly enhanced the inductions of tyrosine aminotransferase (TAT) and ornithine decarboxylase by glucocorticoids, even with sufficient concentration of glucocorticoids to have a maximal effect, whereas it had no effect on TAT activity and increased ornithine decarboxylase activity only slightly in the absence of glucocorticoids. Phorbol derivatives and components of TPA such as 4 beta-phorbol, phorbol 12-tetradecanoate, phorbol 13 acetate, and 4-O-methylphorbol 12-tetradecanoate 13-acetate, which have no tumor promoting activity or ability to activate protein kinase C, did not have any effect on TAT induction by glucocorticoid. TPA enhanced the induction of TAT by various glucocorticoids but had no effect on induction of TAT by glucagon or insulin and did not enhance the induction of glucose-6-phosphate dehydrogenase by 17 beta-estradiol. These results suggest that TPA specifically enhances the induction of TAT and ornithine decarboxylase by glucocorticoids. Similar effects of TPA on TAT induction by glucocorticoid were observed in primary cultures of adult rat hepatocytes. Another activator of protein kinase C, rac-1,2 dioctanoylglycerol, was also found to have similar effects on the cells. PMID- 2887202 TI - Bioenergetics of secretory vesicles. PMID- 2887203 TI - Saturation-transfer studies of ATP-Pi exchange in isolated perfused rat liver. AB - The rate of exchange between inorganic phosphate and ATP was measured in isolated perfused rat livers in the direction of ATP synthesis using 31P NMR spectroscopy and the saturation-transfer technique. Measurement of ATP hydrolysis was not observable, even after treatment of rats with 100 micrograms T3/day per 100 g body wt. When the perfused livers were treated with iodoacetate in order to inhibit glycolysis, NMR measurable exchange between ATP and Pi was eliminated. It is concluded that the inorganic phosphate----ATP conversion detected by saturation transfer is catalyzed by enzymes of the glycolytic pathway and that the mitochondrial ATPase rate is too slow to contribute to the observed effect. PMID- 2887205 TI - The donor specificity and kinetics of the hydrolysis reaction of gamma glutamyltransferase. AB - The donor specificity of the hydrolytic reaction of gamma-glutamyltransferase [5 glutamyl)-peptide:amino-acid 5-glutamyltransferase, EC 2.3.2.2) has been studied by the use of specifically synthesised gamma-glutamyl substrates. It was found that a wide variety of gamma-glutamylated adducts were hydrolysed by the enzyme. The structure of the adduct was relatively unimportant for donor specificity and the enzyme appears to 'recognise' the gamma-glutamyl portion of the donor molecule. In particular the alpha-amino group and the free proton of the gamma peptide bond appear to be essential for donor activity. The Vmax of hydrolysis increased proportionally to the electron-withdrawing capacity of the adduct moiety. The rate of formation of gamma-glutamyl-enzyme intermediate was therefore dependent upon the structure of the adduct of the gamma-glutamyl donor. The results suggest that the enzyme shows little specificity beyond that for gamma glutamyl amides and there is therefore no reason to postulate the presence of a specific glutathione-binding site. PMID- 2887204 TI - Renal brush border glutamine transport: comparison between in situ and isolate membrane vesicle uptake. AB - Glutamine uptake by renal cortical brush-border vesicles was compared to transport expressed by the functioning isolated kidney. Comparisons were made with regard to sodium dependency and the adaptive increase induced by chronic metabolic acidosis in the rat. The results show an absolute dependency upon a sodium gradient; sodium-independent glutamine uptake has no counterpart in situ. In addition, acidosis-induced adaptive increase in vesicle glutamine uptake has no counterpart in situ. Rather, the apparent adaptation reflects extravesicular gamma-glutamyltransferase-mediated conversion to glutamate and subsequent accumulation; acidosis-induced adaptation of this enzyme largely explains the apparent adaptation in glutamine uptake. Consequently the role of membrane transport in glutamine flux regulation can be assessed providing metabolic conversion is controlled. PMID- 2887206 TI - Significance of catalase in peroxisomal fatty acyl-CoA beta-oxidation. AB - Catalase activity was inhibited by aminotriazole administration to rats in order to evaluate the influence of catalase on the peroxisomal fatty acyl-CoA beta oxidation system. 2 h after the administration of aminotriazole, peroxisomes were prepared from rat liver, and the activities of catalase, the beta-oxidation system and individual enzymes of beta-oxidation (fatty acyl-CoA oxidase, crotonase, beta-hydroxybutyryl-CoA dehydrogenase and thiolase) were determined. Catalase activity was decreased to about 2% of the control. Among the individual enzymes of the beta-oxidation system, thiolase activity was decreased to 67%, but the activities of fatty acyl-CoA oxidase, crotonase and beta-hydroxybutyryl-CoA dehydrogenase were almost unchanged. The activity of the peroxisomal beta oxidation system was assayed by measuring palmitoyl-CoA-dependent NADH formation, and the activity of the purified peroxisome preparation was found to be almost unaffected by the administration of aminotriazole. The activity of the system in the aminotriazole-treated preparation was, however, significantly decreased to 55% by addition of 0.1 mM H2O2 to the incubation mixture. Hydrogen peroxide (0.1 mM) reduced the thiolase activity of the aminotriazole-treated peroxisomes to approx. 40%, but did not affect the other activities of the system. Thiolase activity of the control preparation was decreased to 70% by addition of hydrogen peroxide (0.1 mM). The half-life of 0.1 mM H2O2 added to the thiolase assay mixture was 2.8 min in the case of aminotriazole-treated peroxisomes, and 4 s in control peroxisomes. The ultraviolet spectrum of acetoacetyl-CoA (substrate of thiolase) was clearly changed by addition of 0.1 mM H2O2 to the thiolase assay mixture without the enzyme preparation; the absorption bands at around 233 nm (possibly due to the thioester bond of acetoacetyl-CoA) and at around 303 nm (due to formation of the enolate ion) were both significantly decreased. These results suggest that H2O2 accumulated in peroxisomes after aminotriazole treatment may modify both thiolase and its substrate, and consequently suppress the fatty acyl CoA beta-oxidation. Therefore, catalase may protect thiolase and its substrate, 3 ketoacyl-CoA, by removing H2O2, which is abundantly produced during peroxisomal enzyme reactions. PMID- 2887207 TI - Effects of aging on contributions of dietary fat and triiodothyronine treatment to lipogenic enzyme induction. AB - Although lipogenic enzyme inductions are reduced by fat feeding, this reduction decreases with aging and is particularly detectable in the case of acetyl-CoA carboxylase and fatty acid synthetase activities. On the other hand, the fat dependent reductions of malic enzyme and acetyl-CoA carboxylase were consistently relieved by triiodothyronine (T3) treatment. The effects of T3 treatment on these enzyme inductions were greater in 10-month-old rats than in 1-month-old rats, while the carbohydrate-dependent induction and the fat-dependent reduction of the enzymes decreased with aging. In these animals, alterations in malic enzyme mRNA translational activities were roughly in parallel to the enzyme activities. Therefore, the age-dependent alterations in effects of T3 treatment and fat on malic enzyme induction do not appear to occur in post-translation. PMID- 2887208 TI - The effect of analogues of chymostatin on lysosomal and non-lysosomal components of protein degradation in isolated hepatocytes. AB - Of the proteinase inhibitors derived from Streptomyces spp., chymostatin is the most effective inhibitor of non-lysosomal proteolysis. As part of a systematic study of the structural features of the chymostatin molecule that are responsible for this inhibitory activity, a series of fifteen di- and tripeptide analogues of chymostatin were tested for their ability to suppress protein degradation in isolated primary hepatocytes. Protein degradation was assessed in two ways: by the release of radiolabel from proteins prelabelled in vivo (to which both lysosomal and non-lysosomal processes contribute) and by the rate of inactivation of tyrosine aminotransferase, a process that is exclusively non-lysosomal. All inhibitors were relatively non-toxic and did not affect the intracellular ATP levels, although some suppression of gluconeogenesis was observed in the presence of leupeptin, chymostatin or the analogues. Tripeptide phenylalanine aldehydes or semicarbazones were at least as effective as chymostatin in reducing protein degradation, whereas peptide alcohols were relatively ineffective. Replacement of the basic capreomycidine moiety in chymostatin with an arginine residue improved the inhibitory activity but equally, substitution of the arginine residue with an uncharged norleucine residue was without significant effect. The structural features that are optimal for inhibition of chymotrypsin or other serine proteinases (previously defined) are not as critical for inhibition of protein degradation in vivo. PMID- 2887209 TI - Effect of cold-temperature exposure and acclimation on amino acid pool changes and enzyme activities of rat brown adipose tissue. AB - The amino acid pool composition and its concentration ratios with respect to blood and plasma, as well as the activities of alanine, aspartate and branched chain amino acid transaminases, glutamine synthetase, adenylate deaminase and glutamate dehydrogenase have been studied in the interscapular brown adipose tissue of control, 12-h cold-exposed and 15-day cold-acclimated rats. Cold temperature affected the amino acid metabolism and pool composition more intensely after 15 days than after 12-h cold-exposure, even though the patterns of change were very similar in both groups. Cold temperatures induced a decrease in glutamine and an increase in glutamate concentration in the tissue. This probably increased the metabolism of branched chain amino acids and caused a decrease in adenylate deaminase activity. It also seemed to increase alanine utilization. We concluded that amino acid metabolism in brown adipose tissue is enhanced by cold temperature acclimation. PMID- 2887210 TI - Differential effects of stimulus termination on excitation and desensitization of folic acid receptors and guanylate cyclase in Dictyostelium discoideum. AB - The response of guanylate cyclase to addition of extracellular stimuli is well documented. Here we report for the first time the response of guanylate cyclase to removal of stimuli. Three methods were employed to terminate rapidly a stimulus of folic acid. (1) Addition of a highly active folate deaminase preparation, or (2) 12-fold dilution of the stimulated cell suspension, or (3) addition of an excess concentration of a non-agonistic derivative of folic acid, i.e., 2-deaminofolic acid, which chases the folate agonist from its cell-surface receptors. Accumulation of cGMP terminated instantaneously upon addition of deaminase, but degradation of the synthesized cGMP was not observed until 10-12 s after stimulation. Also in a cGMP phosphodiesterase-lacking 'streamer' mutant an instantaneous termination of further cGMP accumulation was observed upon stimulus removal. This suggests that the termination of cGMP accumulation is due to inactivation of guanylate cyclase instead of a steady state of cGMP synthesis and degradation. Further accumulation of cGMP was approx. 75% reduced upon dilution of a cell suspension after stimulation with both agonists. Stimulation by 300 nM folic acid or by 30 nM N10-methylfolic acid (a more potent agonist) yielded identical results. However, upon addition of deaminofolic acid the accumulation of cGMP continued normally if the cells had been stimulated with N10-methylfolic acid, but only slightly in the case of a folic acid stimulus. The effect of stimulus duration on desensitization was monitored; it was observed that 50% desensitization was induced by stimulation for 1 s, while 4 s was sufficient for maximal desensitization. Short stimuli were observed to elicit high levels of desensitization without much excitation of guanylate cyclase. A desensitization like process was observed at the level of the folate-binding chemotactic receptors as well. Relationships between the cGMP response data and folic acid receptor kinetics are discussed. PMID- 2887211 TI - Effects of preformed proline and proline amino acid precursors (including glutamine) on collagen synthesis in human fibroblast cultures. AB - A technique of derivatizing proline and 4-hydroxyproline with 7-chloro-4 nitrobenzo-2-oxa-1,3-diazole was used to measure the radioactivities, concentrations and specific activities of proline and hydroxyproline. The technique was used to study the conditions of procollagen synthesis in cultured human foreskin fibroblasts. Procollagen synthesis appeared to be independent of the proline concentration in the medium, in the presence of glutamine, when monitored by the assay of non-dialyzable hydroxyproline, but not when monitored by [14C]proline incorporation. In the absence of unlabelled proline added to labelled proline in the medium, the specific activity of the secreted procollagen did not reach a plateau over a 24-h period. When the medium was supplemented with glutamine, glutamic acid, or aspartic acid, both the radioactivity and concentration of intracellular free proline decreased. Pyrrolidone-2-carboxylic acid and ornithine both induced a slight increase in concentration of the intracellular free proline. Glutamine competed with [14C]proline for incorporation into prolyl-tRNA and procollagen, independently of free intracellular proline, and it stimulated the biosynthesis of procollagen (expressed as non-dialyzable hydroxyproline) by a factor of 2.3. PMID- 2887212 TI - In vivo and in vitro adenosine stimulation of ethanol oxidation by hepatocytes, and the role of the malate-aspartate shuttle. AB - In this study, a pronounced increase of ethanol oxidation was found in hepatocytes obtained from adenosine-treated rats, or after in vitro additional of the nucleoside; this finding was accompanied by a maintenance of the normal cytoplasmic redox state. These results suggest a higher availability of cytoplasmic NAD in these cells. Therefore, the metabolic pathways which carry out the reoxidation of cytosolic reducing equivalents, namely, malate-aspartate and alpha-glycerophosphate shuttles, were examined. Isolated mitochondria from adenosine-treated rats had an increased NADH oxidation by the malate-aspartate shuttle; furthermore, in vivo and in vitro addition of adenosine to the hepatocytes induced changes in the equilibrium of the malate-aspartate shuttle, as evidenced by the subcellular distribution of the intermediates of this pathway. Acetaldehyde removal was also increased by adenosine and this fact was related to an elevated NAD/NADH ratio in the mitochondria. Thus, under these conditions, an increased ethanol uptake was accompanied by enhanced acetaldehyde removal in the animal. In conclusion, adenosine administration stimulates the transport of cytoplasmic reducing equivalents to the mitochondria, mainly through the malate-aspartate shuttle. This action, which may be located at the level of the mitochondrial membrane, is reflected by an enhancement of ethanol and acetaldehyde oxidations. PMID- 2887214 TI - Endogenous agonists may change the concentration-response curves of exogenous agonists: source of quantitative information about the endogenous tone. AB - The "pharmacological dogma" that competitive antagonists cause parallel shifts to the right with sustained maximum effect of semi-logarithmic concentration response curves of exogenous agonists may not be true if an endogenous agonist is present in the preparation. In this case, the antagonist and the exogenous agonist interfere in a complex way with an existing circuit of regulation between the response and the endogenous agonist. In consequence, it is difficult to determine the true shift in the concentration-response curves as induced by the antagonist, since a deviation of the curves in a non-parallel manner can be observed. The extent of this deviation may be used to learn more about the variables involved. The present paper discusses this phenomenon: The regulatory circuit of the (auto)receptor modulated release of neutrotransmitters is used as an example. Paired samples of data are analysed in this example. Since the extent of the non-parallel deviation also depends on the manner in which the paired samples are mathematically linked, two different ways of data evaluation have been used. A theoretical model of the relation between receptor activation and response is proposed which allows to evaluate experimental concentration-response curves by means of non-linear regression analysis. This evaluation yields quantitative information on the parameters of the regulatory circuit: the concentration of the endogenous agonist, its KD value and the true shift of the concentration-response curve caused by the applied antagonist. PMID- 2887213 TI - [Energizing of F1-ATPase after irradiation with visible light]. AB - It was shown that ATP synthesis by F1-ATPase sensitized by visible light was combined with oxidation of SH groups and decrease of initial flavin fluorescence in the F1-ATPase preparation. It was suggested that it was an endogenous flavin group that regulated redox transitions between SH-S-S groups which was essential for the catalysis in vivo. PMID- 2887216 TI - Benzodiazepines. PMID- 2887215 TI - [Role and place of cyclic nucleotides in the neuroendocrine regulation of cells and tissues]. AB - Cyclic adenosine monophosphate and cyclic guanosine monophosphate occupy one of the central places in the neuro-endocrine regulation in the highest organisms. These nucleotides mediate the effect of most hormones and neurotransmitters: peptide, polypeptide and proteinaceous, catecholamine, histamine, many prostaglandins, acetylcholine (in the case of muscarinic cholinergic receptor activation), endorphins and enkephalins. They regulate also synthesis and secretion of many hormones and neurotransmitters. Cyclic nucleotides play a key role in the functioning of organs of sense (vision, smelling and taste). Under the control of cyclic nucleotides there are main metabolic processes: glycogenolysis and lipolysis. These nucleotides have been shown to participate in the genome expression, in growth, differentiation and proliferation of cells. Accelerating or decelerating the ionic transport across the biological membranes cyclic nucleotides influence the cell bioelectric activity as well its contractility. They may also change the properties of contractile and cytoskeleton proteins, thus interfering in the processes of mobility and shape formation of cells. PMID- 2887217 TI - Pyroglutamyl N-termini of thermal polyamino acids. AB - It has been established indirectly that the N-termini of the thermal polyamino acids are pyroglutamic acid. This was determined by trifluoroacetic acid hydrolysis of the lactam ring followed by Dansyl labelling. The polyamino acids contained Ala, Gly, Glu, Leu, Phe, and Pro. In the experiments described here, the presence of pyroglutamic acid at the N-terminus of a polyamino acid was determined directly by the use of pyrrolidone carboxylyl peptidase. The enzyme catalyzes the removal of pyroglutamyl residues at the N-terminus of polypeptide chains. The polyamino acids used in these studies contained glutamic acid, aspartic acid, alanine, glycine, isoleucine, proline and valine. Alkaline hydrolysis was also used to determine indirectly that the N-termini of these polyamino acids are pyroglutamic acid. Another interesting finding was that many of the amino acids in the polymerization mixture were found to occur penultimate to the N-terminal amino acid. This is interpreted to mean that the diffusible fraction contains many polyamino acids. PMID- 2887218 TI - [Effect of cholinergic stimulation on spontaneous lymphocyte adhesion in vitro]. AB - With the help of spontaneous lymphocyte adhesion test it was demonstrated that acetylcholine and carbacholine enhanced the adhesion of lymphocytes. The enhancement revealed was completely abolished by a specific M-cholinergic blocker -atropine, but not N-cholinergic blocker--hexonium. Thus, the enhancement of spontaneous human lymphocyte adhesion by cholinergic stimulation is mediated by M cholinoreceptors. It is suggested that the phenomenon revealed is mediated by the enhancement of cGMP intracellular levels after cholinergic stimulation. PMID- 2887219 TI - [Protective potential of hematopoietic cells of the embryonic liver during long term culture]. AB - The influence of the duration of the organ cultivation on the protective potential of mouse fetal liver hemopoietic cells was investigated. The protective potential was evaluated according to a 3-week viability of the lethally irradiated (mean LD88/21) mice following syngeneic transplantation. During 20 days of cultivation the protective potential (calculated per number of injected cells) remained at the initial level. With more prolonged cultivation (24-62 days) the protective potential was retained only in part of cultures and the mean effect was reduced. No parallelism has been revealed between the totipotent hemopoietic precursors capable of replacing the hemopoietic cells of an irradiated recipient and the CFUs in long-cultivated fetal liver cultures. PMID- 2887220 TI - [Tyrosine hydroxylase of the blood leukocytes]. AB - Tyrosine hydroxylase activity has been established in blood plasma leucocytes of rat, cat and man. Tyrosine precursors and some nuclear erythroid cells. GFU-GM did hydroxylase activity in leucocytes shows the Km for tyrosine inhibited by high concentrations of L6 tyrosine (substrate inhibition), alpha-methyl-para tyrosine dopamine. The kinetic properties of leucocyte tyrosine hydroxylase are qualitatively similar to the properties of brain tyrosine hydroxylase. PMID- 2887221 TI - [Temperature sensitivity of afferent receptors in the isolated rabbit heart]. AB - Changes in the positive chronotropic effects induced by epicardial irrigation with heated Krebs-Henseleit solution were studied in the isolated rabbit heart before and after intracoronary infusion of a ganglionic blocking agent, Arfonad (10 mg/ml). 2-3 minutes after Arfonad infusion the positive chronotropic effects decreased to 37.9% and 5-10 minutes later they returned to control levels. It is concluded that epicardial surface warming causes an increase in afferent receptor activity. It is suggested that neurogenic component of the positive chronotropic effect may be produced through the activation of intracardiac reflectory pathways. PMID- 2887222 TI - [Neuroimmunoregulatory properties of short protein fragments in rats exposed to immobilization stress]. AB - The influence of short protein fragments on immobilization stress-induced alterations in neuroendocrine and immune systems (catecholamine content in the striatum, hypothalamus and adrenals, serum corticosterone concentration, specific antibody producing activity) was investigated. Immunoglobulin G fragments- tuftsin, rigin, polar amino acid set--polarin and thymus hormone fragment- thymopoetin, as well as substance P (as reference drug) were administered intraperitoneally at doses of 100 and 500 micrograms/kg 30 min before exposure to stress. Rigin and thymopentin showed high stress-protective activity. It is suggested that similar protein fragments, being endogenously formed, may play a regulating role in neuroimmunological homeostasis during exposure to stress. PMID- 2887223 TI - The transglutaminase in vascular cells and tissues could provide an alternate pathway for fibrin stabilization. AB - A thrombin-independent transglutaminase (TG) has been identified in vascular cells and tissues from human, rabbit, rat, porcine, and bovine sources. The vascular TG had several properties that were similar but not identical to guinea pig liver TG. Both enzymes had similar chromatographic and electrophoretic properties, preferentially cross-linked the alpha-chains of fibrinogen, and reacted with polyclonal and monoclonal anti-guinea-pig liver TG antibodies. However, the TG from adult bovine aortic endothelial (ABAE) cells exhibited a novel Ca2+/Mg2+ dependence for enzymatic activity that was distinct from that of purified guinea pig liver TG. The mol wt of the vascular TG (79 +/- 3 kd) determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) was slightly lower than the purified guinea pig liver TG (85 +/- 9 kd). The TG antigen was detected by immunohistochemical techniques in association with the endothelial and smooth muscle cells of arteries, veins, venules, and capillaries. The TG antigen also codistributed with the fibronectin antigen along the hepatic sinusoids. The ABAE cell TG cross-linked alpha 2-plasmin inhibitor to fibrinogen and caused the modified fibrinogen to be 40-fold more resistant to plasminolysis. A thrombin-independent TG in vascular cells of blood vessels could provide an alternate pathway to inhibit fibrinolysis and promote fibrin stabilization. PMID- 2887224 TI - 1986 update of HIV seroprevalence, seroconversion, AIDS incidence, and immunologic correlates of HIV infection in patients with hemophilia A and B. AB - A cohort of 181 patients with hemophilia A (149) and hemophilia B (32) cared for at the Hemophilia Center of Western Pennsylvania was followed to determine human immunodeficiency virus (HIV) seroprevalence, seroconversion rate, and clinical and immunologic correlates of HIV infection. By December 1986, 82 (45%) were HIV seropositive, and of these, ten (12%) had developed AIDS, 28 (34%) had symptomatic HIV infection (CDC class III, IV), of whom 14 (17%) had AIDS-related complex (ARC), and 44 (54%) had asymptomatic HIV infection (CDC class II). The HIV seropositive group included 82% of those treated with factor VIII concentrate (97% severe, 5% moderate), 48% of those treated with factor IX concentrate (92% severe, 8% moderate), 10% of those treated with cryoprecipitate (67% severe, 33% moderate), and none of those treated with fresh frozen plasma. Based on 77 serially sampled HIV seropositive hemophiliacs (1977 to 1986), peak seroconversion occurred in 1982, with 14% (11 of 77) occurring since 1984. With increasing time from seroconversion, both T4 lymphocyte number and function (the latter measured by growth in soft agar [T colony assay]) progressively declined; T4 number declined to 135 +/- 26/mm3 (SEM), and colony count declined 1193 +/- 537 (control 3851 +/- 387) by 5 years after seroconversion. In those developing AIDS, total T4 fell below 100/mm3 (33 +/- 8/mm3) at diagnosis. In this cohort, the overall AIDS incidence is 5.5% (12% among the HIV seropositive) and in those seropositive 5 or more years, the AIDS incidence approaches 32%. PMID- 2887225 TI - Immunoregulatory T-cell defects in B-cell chronic lymphocytic leukemia: cause or consequence of the disease? The contributory role of decreased availability of interleukin 2 (IL-2). AB - Several phenotypic and functional defects have been described within the residual T-lymphocyte population of patients with B-cell chronic lymphocytic leukemia (B CLL), particularly in those in the more advanced stages of the disease. In this study, we review these abnormalities and discuss their possible effects on the course of the illness. Particular emphasis is devoted to the role of interleukin 2 (IL-2) in B-CLL. Evidence is provided that the IL-2 released by B-CLL T lymphocytes may be utilized by the neoplastic B-cell clone that expresses the IL 2 receptor and that decreased availability of IL-2 may play a contributory role in some of the T-cell defects encountered in B-CLL. PMID- 2887226 TI - Recent advances in sympathetic neurotransmission. Proceedings of the 6th meeting on adrenergic mechanisms held in honour of Professor J. Garrett. Porto, Portugal, September 27-30, 1986. PMID- 2887227 TI - Characteristic features of transmitter release from sympathetic nerve terminals. AB - Recently, using intracellular recording techniques, it has been shown that transmitter release from individual varicosities in sympathetic nerves occurs intermittently, and that only a single quantum of transmitter is secreted when the release process of a varicosity is activated by the nerve action potential. Here we discuss results obtained using a novel method of extracellular recording which allows simultaneous measurement of both the nerve action potential and transmitter release from postganglionic sympathetic nerve terminals. We have confirmed that release is intermittent, but the importance of this new approach is that the relationship between the nerve terminal action potential and transmitter release can be studied unambiguously for the first time. Thus, we are able to show unequivocally that: (1) intermittence is caused by a low probability of transmitter release in the invaded varicosity; (2) frequency-dependent facilitation of release is determined by the rate of arrival of the action potential and not by detectable changes in its configuration; (3) the current underlying the exciitatory junction potential (EJP) is brief compared to the total duration of the EJP, and (4) clonidine may inhibit transmitter release by modifying the nerve terminal action potential. These results provide important new insights into the fundamental mechanisms involved in the physiological and pharmacological control of transmitter release from sympathetic nerves. PMID- 2887228 TI - The role of an intergovernmental regional organization in combating drug trafficking: a perspective of the Colombo Plan Bureau. AB - The Colombo Plan was established in 1950 as a regional intergovernmental organization for co-operative economic and social development in Asia and the Pacific comprising 26 member States. The permanent secretariat is the Colombo Plan Bureau to which is attached the Drug Advisory Programme (DAP) headed by a drug adviser, who consults with Governments and helps develop co-operative programmes for drug abuse prevention and control. DAP functions in close liaison and co-operation with organizations of the United Nations system and other regional and international organizations in pursuing activities in line with the international strategy and policies for drug control of the United Nations. DAP assists member States in creating public awareness of the dangers of drug abuse and drug trafficking through the use of mass media, seminars, workshops and conferences and study exchange programmes. It assists Governments in updating their drug laws and in establishing special drug units and national co-ordinating bodies on drug abuse control. DAP encourages and supports the utilization of community resources and the activities of non-governmental organizations and voluntary bodies for the prevention and reduction of drug abuse, as well as the use of mass media for more co-ordinated efforts in this area. It assists member States in developing human resources and technical expertise of personnel in the various disciplines of law enforcement, prevention, treatment and rehabilitation, through training, seminars, study exchange fellowship programmes and research. DAP also assists in promoting co-operation at the regional and interregional levels, and is involved in developing and strengthening co-operation between agencies of member States that deal with drug problems. PMID- 2887229 TI - Orchidopexy: the effect of changing patterns of referral and treatment on outcome. AB - One-hundred and twenty-eight orchidopexies performed between 1979 and 1981 were reviewed in 1985, and the results compared with the results of operations performed in 1972. The age of referral has been determined for 1972, 1979-1981 and 1985. The number of unsatisfactory results has decreased from 35 per cent in 1972 to 9.4 per cent between 1979 and 1981. Five cases of the 'ascending testicle' were discovered, confirming the importance of this phenomenon. We suggest that the optimum age for orchidopexy is during the second year of life; however, during 1985, only 20 per cent of boys referred for orchidopexy were under 3 years of age. Doctors performing neonatal examinations should consider the possibility of cryptorchidism and ensure that affected neonates are reviewed at 1 year. The potential theoretical advantages of orchidopexy at an early age will only be converted into clinical benefit if the operation is performed by an experienced surgeon who has developed an expertise in this area of surgery. PMID- 2887230 TI - Treatment of sensorineural deafness associated with ulcerative colitis. PMID- 2887231 TI - Extrapyramidal disturbances caused by inappropriate prescribing. PMID- 2887232 TI - Renal micropolyarteritis. PMID- 2887233 TI - Influence of progesterone coils (PRID) on some plasma constituents in buffaloes. PMID- 2887234 TI - Sensory and nonsensory ciliated cells in the ear of the sea lamprey, Petromyzon marinus. AB - The inner ear of the sea lamprey, Petromyzon marinus, was examined using scanning and transmission electron microscopy. Many of the nonsensory surfaces of the ear chamber are lined by numerous, noninnervated, multiciliated epithelial cells. Each multiciliated epithelial cell has 43-66 true cilia projecting from its apical surface into the lumen of the ear. Although the cilia leave the cell individually, all of the cilia from a single cell come together just above the apical cell surface and are held together by a cross-network of fibrillar material. The cell bodies of the multiciliated cells sit upon a basal lamina which overlies a collagen-filled matrix. Petromyzon has typical vertebrate sensory hair cells on the cristae of the two semicircular canals as well as on the main sensory epithelium, the macula communis. Cell bodies of the sensory hair cells are similar to hair cells of other vertebrates. However, unlike other fishes, the sensory hair cells in Petromyzon have striated organelles between the nucleus and the apical cell membrane. The hair cells are innervated by afferent and efferent nerve fibers. PMID- 2887235 TI - Inositol phosphate formation and chloride current responses induced by acetylcholine and serotonin through GTP-binding proteins in Xenopus oocyte after injection of rat brain messenger RNA. AB - The molecular mechanism underlying the signal transduction from muscarinic and serotonergic receptors to Cl- channels were investigated in Xenopus oocyte microinjected with rat brain poly(A)+ mRNA. Transient Cl- current responses of the mRNA-injected oocytes to acetylcholine (ACh) and serotonin (5-HT) were similar in amplitude and onset. Although pharmacological characterization indicated that distinct M1-like and S1-like receptors of rat brain are involved in the ACh and 5-HT responses, respectively, these responses cross-desensitized each other completely. A common involvement of the GTP-binding proteins coupled to phosphoinositide breakdown was suggested by the findings that intracellular application of guanosine 5'-O-(2-thio)bisphosphate (GDP beta S) or neomycin greatly suppressed both ACh and 5-HT responses. These responses were not affected by exposure of the mRNA-injected cells to cholera toxin, but they were inhibited by pertussis toxin. The increase in inositol trisphosphate (IP3) responsive both to ACh and 5-HT coincided with the expression of Cl- current responses. However, only 5-HT but not ACh slightly increased the cyclic AMP (cAMP) content of the mRNA-injected cells. Intracellular injection of either IP3 or Ca2+ produced a transient Cl- current in the mRNA-injected cells as well as in non-injected cells, while 1-oleoyl-2-acetylglycerol (OAG), cAMP or cyclic GMP (cGMP) never elicited chloride current responses. It was proposed that muscarinic and serotonergic receptors are commonly linked to phosphoinositide breakdown through the mediation of GTP-binding proteins Ni and/or No in mRNA-injected oocytes. PMID- 2887236 TI - Regulation of tyrosine hydroxylase gene expression during differentiation of neuroblastoma cells. AB - Differentiation of N1E-115 neuroblastoma cells into neuron-like cells, with extension of neurites and acquisition of excitable membranes, can be induced by dimethyl sulfoxide (DMSO). We have found this differentiation to be accompanied by an increase in tyrosine hydroxylase (TH) mRNA, an increase disproportionate to changes in mRNAs for other measured, non-neuron-specific genes. The mRNA increases slowly over several days and falls gradually after removal of DMSO. Nuclear run-on studies suggest that a change in the rate of transcription cannot explain the increase in steady-state mRNA levels. TH mRNA half-life does, however, increase. This suggests that regulation is exerted in this case not at the level of transcription but rather at that of mRNA stability. PMID- 2887238 TI - Slow EPSP and the depolarizing action of noradrenaline on sympathetic preganglionic neurons. AB - Intracellular recordings were made from sympathetic preganglionic neurons of the lateral horn in slices of cat thoracic cord maintained in vitro. Focal electrical stimulation of the slice evoked, in addition to the already described fast EPSPs, EPSPs of several seconds duration. The slow EPSPs, like the fast EPSPs, were graded with stimulus intensity and were abolished by TTX or low Ca and high Mg superfusion. The slow EPSP decreased in amplitude with membrane hyperpolarization and was nullified at -90 mV but did not reverse with further hyperpolarization. The slow EPSP was abolished by phentolamine or prazosin but not by yohimbine. Noradrenaline NA, 10-50 microM) caused in 30% of neurons a TTX-resistant depolarization. The NA-evoked depolarization had the same characteristics as the slow EPSP with respect to sensitivity to membrane potential and to adrenergic blockers. These results suggest that NA, acting on an alpha 1-receptor, may be the mediator of the slow EPSP evoked in this neuron by focal stimulation. PMID- 2887237 TI - Stimulation of the locus coeruleus decreases arterial pressure. AB - Unilateral microinjection of L-glutamate (L-Glu, 0.5-5 nmol) into the locus coeruleus (LC) of rats anesthetized with chloralose elicited decreases in blood pressure and heart rate. The maximal depressor response elicited by injection of L-Glu into the LC was approximately 30 mmHg, and the maximal bradycardic response was approximately 35 bpm. Microinjections into the LC of DL-homocysteic acid (1 nmol) and carbachol (1 nmol), agents which (like L-Glu) stimulate neurons within the LC, also produced depressor and bradycardic responses. Vagal blockade with methyl atropine eliminated the bradycardic response, but had no effect on the decrease in arterial pressure elicited by stimulation of neurons within the LC. Destruction of the noradrenergic neurons of the LC by local administration of 6 hydroxydopamine eliminated the cardiovascular responses elicited by injection of L-Glu or carbachol into the LC. These results are in direct contrast to the pressor response elicited by electrical stimulation of the region containing the LC. Destruction of the LC with 6-hydroxydopamine, which totally eliminated the depressor response to L-Glu, slightly potentiated the pressor response elicited by electrical stimulation of this region. Electrical stimulation of the region containing the LC has also been reported to increase plasma vasopressin levels; this response could not be reproduced by by stimulation of the LC by microinjection of L-Glu. These results indicate that stimulation of the noradrenergic neurons of the rat LC decreases arterial pressure and heart rate. Furthermore, these results suggest that the pressor response elicited by electrical stimulation of this region is not due to stimulation of neurons of the LC. PMID- 2887239 TI - A vasoactive intestinal polypeptide system in retinal cell cultures: immunocytochemistry and physiology. AB - The purpose of this study was to search for vasoactive intestinal polypeptide (VIP)-like immunoreactivity and VIP-mediated effects in cultures containing cells from the mammalian retina. VIP-like immunoreactivity was detected by indirect immunocytochemistry within 6 days after plating dissociated retinal cells from embryonic day-19 rats. In electrophysiological experiments, VIP was found to facilitate evoked transmission at cholinergic synapses formed by retinal neurons in culture. PMID- 2887240 TI - Characterization of quisqualate-type L-glutamate receptors in the retina. AB - In the vertebrate retina excitatory transmission seems to be mediated mainly by excitatory amino acids; glutamate and/or aspartate are the most viable candidates to subserve this function. Postsynaptic receptors for N-methyl-D-aspartate (NMDA), kainate (KA), quisqualate (QA) and 2-amino-4-phosphonobutyric acid have been electrophysiologically identified. In this work we have tried to identify and characterize QA receptors through the binding of the most specific analogue available for this receptor: [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4 propionic acid ([3H]AMPA). AMPA binding to retinal membranes was sodium- and temperature-independent, with optimum pH at 6-7. Ligand-receptor interaction was reversible and saturable. Pharmacologically, glutamate analogues were more active displacers than NMDA analogues: AMPA greater than (RS)-3-hydroxy-4,5,6,7 tetrahydro-isoxazolo-(5,4-C)-pyridine-7-car boxylic acid = L-Glu = QA; with IC50 in the low microM range. Glutamic acid diethylester was uneffective while KA and cis-2,3-piperidine dicarboxylate were potent inhibitors of binding. Binding was stereospecific, L-isomers being more effective displacers than D-forms. Subcellular distribution showed binding concentrated in the inner plexiform layer (IPL), but also present in the outer plexiform layer (OPL). Kinetics of [3H]AMPA binding showed a high affinity kB = 1-2 microM in membranes from complete retina, IPL and OPL, with binding sites concentrated in P2 (Bmax = 16.2 pmol/mg protein). Our results provide biochemical evidence for the presence and distribution of physiologically relevant QA receptors in the chick retina which is in agreement with previous physiological findings. PMID- 2887242 TI - A L-[3H]glutamate binding site on glia: an autoradiographic study on implanted astrocytes. AB - In the present study cultured astrocytes were implanted into the inferior colliculus of rats to create an astrocyte-enriched field that could be examined autoradiographically. The presence of the astrocytes was confirmed with anti glial fibrillary acidic protein (GFA) immunocytochemistry. We report the presence of a chloride-dependent glutamate binding site on the implanted astrocytes. In the presence of chloride, the specific glutamate binding detected in the implant area was 5-fold greater than that found in a corresponding contralateral region. When the chloride was replaced with acetate, glutamate binding to the astrocytes decreased by more than 80%. The chloride-dependent binding to the astrocytes was insensitive to inhibition by kainic acid (KA) and N-methyl-D-aspartate (NMDA) and sensitive to quisqualate, L-aspartate, L-2-amino-4-phosphonobutyrate, and L-alpha aminoadipate. The pharmacology of the binding was very similar to that of the in vitro glutamate binding to membranes from cultured astrocytes and to that of a chloride-dependent transport system identified in a glioma cell line. We conclude that the interaction of glutamate with astrocytes is an important component of the total glutamate binding observed in brain slices. PMID- 2887241 TI - Synergistic action of thyroid hormone, insulin and hydrocortisone on astrocyte differentiation. AB - We report here on the synergistic regulation of astrocyte development by 3 hormones: thyroid hormone (TH), insulin, and hydrocortisone (HC). Their effect, in a defined serum-free media, on astrocyte morphology, on glia fibrillary acidic protein (GFAP) immunostaining pattern, and on glutamine synthetase (GS) was investigated. TH transformed the flat, polygonal astrocytes into process-bearing cells. This effect was accentuated by insulin, which by itself had no effect on astrocyte morphology. The morphological transformations were accompanied by changes in the pattern of GFAP immunostaining which indicated a more organized and directed cytoskeleton arrangement in the TH-insulin treated cultures. Over 95% of the cells in the culture expressed GFAP. All 3 hormones regulated GS levels. TH increased GS levels by 50% and insulin raised its levels by 3-fold. While having no effect on astrocyte morphology, HC increased GS levels by 3.7 fold in both the hormone-free and insulin-supplemented medium. HC acted synergistically with insulin in its action on GS bringing about a 12-fold increase in the enzyme activity. In contrast, TH did not interact with insulin and was additive with HC in its action on GS. The continuous presence of insulin and TH was required to maintain their morphological and GS effect, suggesting that these hormones might not only be important for astrocyte differentiation, but later on for astrocyte function as well. Since astrocytes interact with and affect neurons and oligodendrocytes, the findings reported here might have bearing on the development and function of these other brain cells as well. PMID- 2887243 TI - Effects of selective and non-selective kappa-opioid receptor agonists on cutaneous C-fibre-evoked responses of rat dorsal horn neurones. AB - We have studied the effects of 3 putative kappa-opioid receptor agonists, U50488H, ethylketocyclazocine (EKC) and dynorphin A1-13 (DYN) on the processing of nociceptive information in the dorsal horn of the rat under halothane anaesthesia. Extracellular single unit recordings were made from convergent or multireceptive lumbar dorsal horn neurones, which could be excited by impulses in A beta and C fibre afferents following transcutaneous electrical stimulation of their ipsilateral hind paw receptive fields and also by noxious and innocuous natural stimuli. Agonists were applied directly onto the surface of the spinal cord. DYN and U50488H consistently produced both a facilitation and inhibition of the C-fibre evoked nociceptive responses of individual cells, these dual effects being relatively insensitive to naloxone antagonism and cancelled each other for the whole population of cells. A beta fibre-evoked responses were little altered. In contrast, EKC consistently depressed C-fibre transmission in a dose-dependent, naloxone reversible manner, analogous to, but considerably less potent than intrathecal morphine under identical experimental conditions. Agonist-induced effects on neuronal responses to natural stimulation (noxious pinch and innocuous prod) were consistent with the changes observed with the electrically evoked responses. The present results therefore indicate that EKC probably exerts its spinal antinociceptive activity in the rat spinal cord in a manner akin to mu receptor activation. Results with U50488H and DYN indicate that -opioids can excite and inhibit individual neurones but produce no overall change on the whole population, so differing from effects mediated by the other opiate receptors. PMID- 2887244 TI - Tyrosine hydroxylase-like immunoreactivity is distributed in the matrix compartment of normal human and Huntington's disease striatum. AB - Tyrosine hydroxylase-like immunoreactivity (TH-lir) was examined in the adult human neostriatum and found to be heterogeneously distributed. Comparison of TH lir with adjacent sections stained for acetylcholinesterase (AChE) activity showed that TH-lir is confined to the AChE-rich matrix compartment. TH-lir persists within the matrix zone, which is reduced in Huntington's disease (HD), suggesting that the nigrostriatal AChE projection may contribute to the persistent AChE patch-matrix pattern in HD. Despite marked striatal atrophy, the density of TH-immunoreactive fibers and terminals remained unchanged. This represents a loss of TH-positive extrinsic afferents in HD proportionate to striatal atrophy. PMID- 2887245 TI - Pertussis toxin blocks presynaptic glutamate receptors--a novel 'glutamateB' receptor in the lobster neuromuscular synapse. AB - Topical application of L-glutamate to the neuromuscular synapse of the lobster walking leg induced K+-dependent hyperpolarization in the presynaptic membrane. This presynaptic glutamate potential (PGP) was insensitive to Joro spider toxin (JSTX), a spider toxin which specifically blocks the postsynaptic glutamate receptor, but was blocked by pertussis toxin island activating protein (IAP) in a dose-dependent manner. IAP had little effect on the resting conductance channels in pre- and postsynaptic membranes. GTP gamma S, a hydrolysis-resistant analogue of GTP, reduced the PGP supporting the involvement of G-protein in generation of K+ activation. The results suggest that a new type of glutamate receptor exists in the presynaptic membrane in the crustacean neuromuscular synapse. PMID- 2887246 TI - Somatostatin-like immunoreactivity (SLI) in cisternal cerebrospinal fluid of rats kindled by pentylenetetrazol. AB - Somatostatin-like immunoreactivity (SLI) was measured in cerebrospinal fluid (CSF) of rats kindled by pentylenetetrazol (PTZ) (35 mg/kg, i.p., daily) and saline-injected controls. Interictally the levels of SLI did not differ between the groups. Five minutes after the PTZ-induced generalized convulsion the amount of SLI released into CSF was higher (173%, P = 0.006) in kindled rats than in controls, which agrees with previous findings about elevated brain levels of SLI in kindling. PMID- 2887247 TI - Tyrosine hydroxylase-like immunoreactivity and catecholamine fluorescence in ciliary ganglion neurons. AB - In the ciliary ganglia of monkeys, dogs, cats and rats, some neuronal perikarya exhibited tyrosine hydroxylase-like immunoreactivity; neither dopamine-beta hydroxylase-like immunoreactivity nor phenylethanolamine-N-methyltransferase-like immunoreactivity was found in perikarya. Some perikarya of ciliary ganglion neurons displayed catecholamine fluorescence; the fluorescent perikarya were significantly increased in number in dogs injected with nialamide. Thus the existence of dopamine-containing ciliary ganglion neurons was suggested. PMID- 2887248 TI - Leukotrienes C4 and D4 stimulate the release of luteinizing hormone-releasing hormone from rat median eminence in vitro. AB - The release of luteinizing hormone-releasing hormone (LH-RH), somatostatin (SRIF) and growth releasing factor (GRF) by male rat median eminences (MEs) incubated in vitro for 30 min, in the presence of leukotrienes (LT) C4, D4, E4 and B4 was estimated by radioimmunoassay (RIA). Leukotrienes, with the exception of LTE4 stimulated the release of LH-RH. The dose-response curve was bimodal for LTC4 with two maxima at 10(-8) and 10(-16) M (X2.2 and 1.9, respectively), biphasic for LTD4 with a maximum (X2) at 10(-8) M; LTB4 was active only at 10(-6) M (X1.9). These different curves suggest a specific effect on the release of LH-RH. Moreover, these effects were selective since no alteration of SRIF and GRF secretions was observed. No additive effect on LH-RH release was observed when LTC4 and LTD4 were added simultaneously at 10(-8) M. FPL-55712, a drug supposed to be an antagonist of LTC4, showed an unexpected stimulatory effect (X4.2 and 1.7-fold) on LH-RH release at 3.10(-5) and 10(-6) M, respectively. However, FPL 55712 did not alter the release of LH-RH induced with 10(-8) or 10(-16) M LTC4. These results extend our previous observations on the stimulatory action of LTC4 and are the first evidence of the stimulatory effect of LTD4 and LTB4 on the LH RH release. PMID- 2887249 TI - Development of gamma-aminobutyric acid (GABA)ergic neurons in cerebral cortical neurons in primary culture. AB - The developmental patterns of gamma-aminobutyric acid (GABA)ergic neurons in primary culture obtained from the neopallium of 15-day-old fetus of mouse were investigated in terms of morphological features, GABA metabolism and GABA receptor binding. Morphological investigations revealed that these cells possessed typical features of neurons and the formation of synapses was detected at 10 days after the inoculation. During neuronal growth on polylysine surfaces, GABA contents and activity of GABA transaminase (GABA-T) showed a progressive increase in the time of culture. Similarly, L-glutamic acid decarboxylase (GAD) showed a progressive elevation during neuronal development in vitro, which corresponded well with the change in immunoreactivity to anti-GAD examined immunohistochemically. In addition, the high K+-evoked release of [3H]GABA also showed an enhancement during the growth in vitro. The numbers of binding sites (Bmax) for [3H]muscimol and [3H]flunitrazepam (FLN) also showed increases with the time of incubation, although affinity (Kd) to the labeled ligands did not show any noticeable changes. Moreover, it was observed that [3H]FLN binding was enhanced by GABA even in neurons cultured for 7 days. These results indicate that cerebral cortical neurons in primary culture possess GABA biosynthesizing and degrading systems including a high-affinity uptake mechanism for GABA. The present results also indicate that these cells possess synaptic contacts as well as GABAA receptors coupled with benzodiazepine receptor from a relatively early stage of cellular development. PMID- 2887250 TI - An endogenous ligand of the brain sigma/PCP receptor antagonizes NMDA-induced neurotransmitter release. AB - The present study provides evidence for the presence of an endogenous ligand for the phencyclidine (PCP) receptor of mammalian brain. Partially purified bovine hippocampal extracts potently and dose dependently inhibit binding to PCP receptors of [3H]N-(1-[2-thienyl]-cyclohexyl)piperidine (TCP), a highly potent and specific ligand of PCP receptors. In addition to demonstrating PCP-like binding properties, the partially purified extract mimics biological actions of PCP upon neurotransmitter release. HPLC fractions active in the [3]TCP binding assay, by contrast to fractions inactive in the binding assay, potently elicited stimulation of spontaneous acetylcholine and dopamine efflux and inhibited NMDA stimulated release of acetylcholine and dopamine. The transmitter release assay provides validation of a PCP-like physiological activity exerted by bovine hippocampal extracts partially purified by HPLC. PMID- 2887251 TI - Acute ethanol alters the firing pattern and glutamate response of cerebellar Purkinje neurons in culture. AB - Modified explant cultures derived from the cortical region of fetal rat cerebellum, and extracellular recording techniques were used to examine the sensitivity and response of cerebellar neurons, isolated from extracerebellar afferent input, to acute ethanol (EtOH) exposure. Recordings were made from Purkinje neurons (PNs) and granule cells maintained in culture for several weeks, with the emphasis on the PN. Both the PNs and granule cells exhibited spontaneous activity in culture, but, unlike the PNs, not all of the granule cells were spontaneously active. The majority of PNs studied exhibited a high frequency, regular simple spike firing pattern, previously shown to be endogenously generated by voltage-sensitive mechanisms intrinsic to the PN. The granule cells exhibited slow, irregular patterns of activity. EtOH at doses as low as 22 mM (100 mg%), a concentration that reflects blood levels during EtOH intoxication, altered the spontaneous activity of both neuronal types, demonstrating that EtOH has direct actions on cerebellar neurons. In the PNs, acute EtOH (20-80 mM) produced an increase in the regularity of the spontaneous activity and either a transient increase or no change in firing rate. Acute EtOH also significantly altered the response of PNs to the excitatory transmitter glutamate. In the granule cells, acute EtOH altered firing pattern with small and variable effects on firing rate. These data demonstrate that there are multiple sites of EtOH action in the cerebellum and that changes in PN activity with acute EtOH exposure may occur via direct actions on the PN and indirect actions via synaptically connected cerebellar neurons. The demonstration of EtOH-sensitive sites intrinsic to the cerebellum suggests that EtOH actions at these sites contribute to alterations in PN activity that occur in vivo after acute EtOH exposure. PMID- 2887252 TI - Differential mechanisms involved in the anticonflict action of benzodiazepines injected into the central amygdala and mammillary body. AB - The present study was designed to clarify the mechanism of action of benzodiazepines (BDZ) injected into the central amygdala (ACE) and mammillary body (MB). When gamma-aminobutyric acid (GABA) at doses of 30 and 70 micrograms, muscimol (0.01 and 0.03 microgram), valproate (200 micrograms), atropine (20 micrograms) and cyproheptadine (3 micrograms) were bilaterally injected into ACE, a significant and marked increase in the punished responses of conflict schedule was observed. These drugs injected into MB failed to increase the punished responses. In MB, only noradrenaline (NA, 20 micrograms) showed the anticonflict action. NA 20 micrograms also produced the anticonflict action in ACE. These results suggest that the mechanism of anticonflict action of BDZ is different in brain areas. The GABA-ergic, cholinergic, serotonergic and NA-ergic systems seem to be involved in the mechanism of anticonflict action of BDZ in ACE. While the NA-ergic system appears to be operative in MB. PMID- 2887254 TI - Isolated deficiency of tyrosine hydroxylase immunoreactivity in tuberoinfundibular neurons in pituitary prolactin-deficient Snell dwarf mice. AB - Light microscopic morphology and relative numbers of tyrosine hydroxylase (TH) immunoreactive neurons were assessed in hypothalamus of hypopituitary Snell dwarf mice, compared with normal mice of the same strain. Qualitatively, a specific deficit in staining of tuberoinfundibular neurons was noted in dwarf hypothalamus; TH-positive terminals were absent in dwarf median eminence, and morphology of axons in this region was aberrant. Qualitative observations were supported by quantitative assessment of hypothalamic dopaminergic neuron groups. Dorsal and intermediate TH-positive cells numbered 80% of those normal mouse brain; tuberoinfundibular (A12) TH-positive neurons in dwarf hypothalamus were 2% of those in normal mouse brain. The results imply that absence of pituitary hormone feedback impedes both structural and biochemical development of hypophysiotropic hypothalamic neurons. PMID- 2887253 TI - Septo-hippocampal neurons: altered properties in the aged rat. AB - The septo-hippocampal pathway is one of the best characterized cholinergic pathways of the mammalian central nervous system. It is very likely that this pathway is involved in the pathophysiology of dementia of the Alzheimer's type and perhaps of normal aging also. The properties of the septo-hippocampal neurons identified by their antidromic response to the electrical stimulation of the fimbria-fornix were altered in aged (27 months) rats as compared to young (2-3 months) controls: their pattern of spontaneous activity (including the frequency of occurrence of a rhythmically bursting activity) and their axonal conduction velocity were altered. The intensity of these changes was dependent on the presence of pituitary tumor which developed spontaneously in about 1/3 of the animals. These results provide direct evidence of the involvement of septo hippocampal neurons in the aging process. PMID- 2887255 TI - Alpha-melanocyte stimulating hormone discloses a stimulatory effect of beta endorphin on somatostatin release. AB - The influence of alpha-melanocyte stimulating hormone (alpha-MSH) and beta endorphin (beta-END) on the secretion of somatostatin (SRIF) from the median eminence (ME) was studied using an in vitro incubation system. The MEs from adult male rats were first preincubated at 37 degrees C for 30 min with constant shaking in 0.4 ml of Krebs-Ringer bicarbonate-glucose buffer (pH 7.4) containing bacitracin in an atmosphere of 95% O2/5% CO2. Medium was discarded and replaced by medium containing different doses of alpha-MSH, beta-END, or a fixed dose of alpha-MSH (10(-7) M or 10(-9) M) plus beta-END at various concentrations. By themselves alpha-MSH and beta-END did not alter basal SRIF release, but in the presence of alpha-MSH (10(-7) M) beta-END stimulated somatostatin release. This effect was significant at concentrations of beta-END of 10(-8) M and higher. The permissive effect of alpha-MSH was observed at a concentration as low as 10(-9) M, but in this case the stimulatory effect of beta-END became evident only at higher doses tested (10(-7) M). It is suggested that alpha-MSH and beta-END participate in the modulation of SRIF release. By themselves beta-END and alpha MSH did not affect basal release of SRIF but in the presence of alpha-MSH, beta END had a stimulatory effect on SRIF release. The mechanism for this interaction is unknown. The results are consistent with the possibility that beta-END neurons have stimulatory and inhibitory effects on SRIF release and that alpha-MSH, by blocking the inhibitory components, discloses the stimulatory effect of beta-END on SRIF release. PMID- 2887256 TI - Reduction of common carotid resistance upon stimulation of an area dorsal to the facial nucleus of cats. AB - In chloralose-urethane-anesthetized cats, electrical stimulation and glutamate injection on a small reticular area just dorsal to the facial nucleus (DFA) elicited an ipsilateral reduction in the common carotid resistance (CCR reduction) with no or minimal change in other cardiovascular parameters. CCR reduction was mediated via facial and glossopharyngeal nerves, involving partially muscarinic and partially non-muscarinic mechanisms. PMID- 2887258 TI - Hypoxia-ischemia produces focal disruption of glutamate receptors in developing brain. AB - We examined the impact of a perinatal hypoxic-ischemic insult on the distribution of glutamate receptors in developing brain. We used a well characterized rodent model for perinatal hypoxic-ischemic encephalopathy, unilateral carotid artery occlusion followed by exposure to 8% oxygen for 2.5 h in 7-day-old rat pups. This preparation results in focal neuronal damage in striatum, hippocampus, and cortex ipsilateral to ligation. Alterations in the regional distribution of glutamate binding in the first 24 h after the insult were assessed with quantitative in vitro [3H]glutamate autoradiography. In lesioned animals, we found progressive selective reductions in [3H]glutamate binding in forebrain ipsilateral to ligation in regions destined for neuronal damage. The earliest and most prominent unilateral reductions in binding were noted in the dentate gyrus of hippocampus ( 45 +/- 9%, compared with contralateral hemisphere at 24 h). Acute reductions in specific glutamate binding appear to be a sensitive marker for hypoxic-ischemic neuronal damage in the immature brain. These observations suggest that neurons bearing glutamate receptors may be particularly susceptible to hypoxic-ischemic injury. PMID- 2887257 TI - Potassium-evoked release of endogenous primary amine-containing compounds from the trout saccular macula and saccular nerve in vitro. AB - An in vitro preparation of the trout saccular macula, containing a large number of hair cells, served as a potential source of neurotransmitter(s) released at the acousticolateralis hair cell-afferent nerve synapse. An in vitro preparation of the saccular nerve, maintained in parallel, served to indicate the potential neural contribution to overall release from the macula. Efflux of 27 primary amine-containing compounds from the macula and nerve fractions was monitored by cation-exchange HPLC with fluorescence detection, and release by 53.5 mM potassium was determined at 1.45 mM calcium, 0.35 mM magnesium or 0 mM calcium, 10.1 mM magnesium. Taurine was released from the saccular macula in the greatest amount, accounting for 72% of the total evoked release of primary amine containing compounds. Its release was calcium dependent and its time course prolonged. The contribution by myelinated nerve and associated Schwann cells within the macula to overall release of taurine from the macula in the presence of calcium, as determined from the saccular nerve preparation, was only 2%. Other components specifically released from the macula included ethanolamine, phosphoserine, beta-alanine, and glycine. Glutamate and aspartate were released from both the macula and saccular nerve fractions by potassium in the presence of calcium and in a ratio of 6:1 (glutamate:aspartate) for the macula and 7.5:1 for the nerve. The release of aspartate, but not that of glutamate, was lowered in saline containing 0 mM calcium, 10.1 mM magnesium. The calculated contribution from neural elements to overall release from the macula was 10% for aspartate and 18% for glutamate. These studies demonstrate that both the macula and saccular nerve fractions release the 'excitatory neurotransmitter' candidates aspartate and glutamate. Calcium-dependent, potassium-evoked release of taurine appears to be specific to the hair cell-supporting cell population of the saccular macula, and taurine may, therefore, be involved directly or indirectly in hair cell neurotransmission in labyrinthine organs. This study represents the first detailed biochemical characterization of efflux and release for an in vitro hair cell system of relatively high purity with respect to hair cells. PMID- 2887259 TI - Postnatal development of the chemosensitivity of rat cerebellar Purkinje cells to excitatory amino acids. An in vitro study. AB - In vitro sagittal slices of immature rat cerebellum were used to study the development of the sensitivity of Purkinje cells (PCs) to L-aspartate (L-Asp), L glutamate (L-Glu) and related derivatives. As early as postnatal day 0 all PCs already displayed clear excitatory responses to short iontophoretic applications of L-Asp, L-Glu and quisqualate while in the same conditions no effect of N methyl-D,L-aspartate (NMDLA) was detected. By postnatal day 5, i.e. after the onset of the synaptogenesis, the sensitivity of PCs to L-Asp, L-Glu and quisqualate significantly increased up to values similar to those recorded in adult rat cerebellum and surprisingly nearly all (87%) the recorded cells now also displayed excitatory responses to NMDLA. Although this sensitivity of PCs to NMDLA was significantly lower than that observed with the other drugs, it persisted until the end of the first postnatal month when the adult type of connectivity is already well established but at this stage only 30 per cent of the tested cells were still sensitive to the agonist. During this period, excitatory responses elicited by NMDLA were selectively antagonized by 2-amino-5 phosphonovalerate (2-APV), suggesting that during postnatal development, NMDA receptor types are transiently expressed on PCs membranes since in the adult, NMDLA no longer had an excitatory effect. Instead, this drug now exerted a preferential antagonistic action on the excitatory response elicited by L-Asp. Also in the adult, no major changes occurred in the sensitivity of PCs to L-Asp, L-Glu and quisqualate when these drugs were ejected at a dendritic site whereas, when ejected at the somatic level, the sensitivity of the cell appeared 2-3 times lower. PMID- 2887261 TI - cGmp synthesis in cultured cerebellar neurons is stimulated by glutamate via a Ca2+-mediated, differentiation-dependent mechanism. AB - Sensitivity of cyclic GMP synthesis to stimulation by excitatory amino acids, depolarizing agents, and divalent cation ionophores develops during the differentiation of cerebellar neurons in culture; in each case calcium influx appears responsible for activating guanylate cyclase. The developmental event being followed is not the appearance of either the soluble or the particulate form of the enzyme since both are present throughout. The possible role of a differentiation-dependent calcium-modulating protein is discussed. PMID- 2887260 TI - Development of somatostatin immunoreactive neurons in rat retina. AB - Levels of somatostatin-like immunoreactivity (SLI) were measured in the rat retina by radioimmunoassay during prenatal and postnatal development. SLI containing cells were visualized by immunocytochemistry throughout this time period. SLI is present as early as embryonic day 15 (E15) and by E16 at concentrations 10-fold (4.4 +/- 1.4 pg/micrograms protein) higher than the adult retina, and the SLI is confined to cells in the inner neuroblastic layer. As the inner plexiform layer (IPL) develops (E17-18), the level of SLI falls (2.0 pg/micrograms protein) and distinct SLI neurites are seen throughout the inner neuroblastic layer. At birth (P0), the SLI level continues to decline at a time when cells are migrating. Few immunoreactive cells are seen in the developing ganglion cell layer (GCL), presumably as a result of this migration. At postnatal day 4 (P4), the amount of SLI continues to decline, and very few immunoreactive cells are noted. At P8, distinct cells contain SLI both in the GCL and inner nuclear layer (INL). SLI then increases as the retina matures postnatally. After eye opening, the amount of SLI approaches adult levels and the immunocytochemical pattern is similar to that reported for the adult rat retina; i.e. SLI is confined to two subpopulations of cells, one in the INL and one in the GCL. The early prenatal appearance of SLI suggests that it may play a role in retinal development. PMID- 2887262 TI - A cardioinhibitory area in the midbrain central tegmental field of cats. AB - A cardioinhibitory area in the central tegmental field of the midbrain (CIM) was studied in cats under chloralose-urethane anesthesia. Electrical and chemical (glutamate and DL-homocysteic acid) stimulations in this area produced marked bradycardia accompanied by mostly hypotension or minimal change in arterial pressure and by occasional hypertension particularly in the dorsal portion. CIM excitation potentiated the reflex bradycardia induced by IV phenylephrine, while bilateral electrolytic lesion of CIM neither changed the resting cardiovascular parameters nor the reflex bradycardia. The CIM bradycardia was not affected by supracollicular decerebration, but substantially reduced by unilateral vagotomy and completely eliminated by bilateral vagotomy. Destruction of the ambiguus nucleus (NA) and solitary and dorsal motor nuclei (NTS/DMV) abolished the bradycardia. Midline bisection at the midbrain-pontine level only slightly reduced the bradycardia while at the medullary level it was moderately attenuated. Electrolytic lesion of the cardioinhibitory area in gigantocellular reticular nucleus (GRN) abolished the bradycardia. These findings suggest that CIM is an independent mechanism which may send axons to GRN from which the axons may in turn synapse with the NTS/DMV complex and NA. Its final output may utilize both vagus nerves to modulate baroreceptor reflex in promoting bradycardia. PMID- 2887263 TI - Locally applied progesterone metabolites alter neuronal responsiveness in the cerebellum. AB - Ongoing studies in this laboratory have demonstrated that both systemically and locally administered sex steroids 17 beta estradiol (E2) and progesterone (P) alter cerebellar Purkinje cell responses to microiontophoretically applied amino acid neurotransmitters GABA and glutamate (GLUT) in the urethane-anesthetized, ovariectomized adult rat. In the present study, we have examined the effects of several locally pressure ejected P metabolites on Purkinje cell responsiveness to GABA and GLUT: 5 alpha-pregnane-20-one (5 alpha DHP), 5 alpha-pregnane-3 alpha-ol 20-one (3 alpha OH-DHP) and 5 alpha-pregnane-3 beta-ol-20-one (3 beta OH-DHP). GABA-induced inhibition was markedly enhanced immediately after onset of local application of 3 alpha OH-DHP or 5 alpha DHP, unaccompanied by alterations in background discharge. Both metabolites also attenuated excitatory responses to GLUT by 0-3 min after initiation of steroid application. In both cases, recovery to control levels of response was observed 6-9 min after termination of pressure application. These results are similar to those seen after local or systemic injection of P. In contrast, 3 beta OH-DHP did not produce any alteration in Purkinje cell responses to either amino acid. As 5 alpha DHP and 3 alpha OH-DHP can be localized in cerebellar tissue after P administration, the results presented here suggest that the neuronal effects of systemic P may be mediated by local membrane actions of P or its metabolites. PMID- 2887264 TI - [Existence of immunoreactivity to GABA in dopaminergic amacrine cells of the rat retina]. AB - Two different immunohistochemical double labelling techniques have allowed the demonstration of a GABA-immunoreactivity in the dopamine amacrine cells of the rat retina. The functional implications of such a colocalization are of importance because antagonist effects of these two neurotransmitters on retinal horizontal cells have been demonstrated. PMID- 2887265 TI - [Proposal of a new analgesia test based on the observation of nociceptive behavior induced by electric stimulation of dental pulp in the rat]. AB - Dental pulp was electrically stimulated in the awake rat. When the stimulus intensity was progressively increased the following four nociceptive reactions successively appeared: jaw opening reflex, scratching, head rotation, vocalization. The threshold of these four reactions was observed before and after administration of three antalgic drugs. No action of the three drugs was observed for the jaw opening reflex. However each drug showed different actions on the other three reactions. PMID- 2887267 TI - Differences in presynaptic action of 4-aminopyridine and tetraethylammonium at frog neuromuscular junction. AB - 4-Aminopyridine markedly potentiates transmitter release at the frog pectoris neuromuscular junction by increasing the quantal content even when applied at low concentrations (5-20 microM). This enhancement of transmitter release is associated with greater minimum synaptic latency, but the dispersion of the synaptic latencies does not appear much affected. This is in contrast with the action of tetraethylammonium (0.2-0.5 mM) in which case similar enhancement of transmitter release results not only in larger minimum synaptic latency but also in greater dispersion of the synaptic latencies. The time course of transmitter release associated with enhanced transmitter output is hence much more prolonged in the presence of tetraethylammonium than 4-aminopyridine, at least for low concentrations of 4-aminopyridine (5-20 microM). This indicates that their presynaptic actions differ significantly. This conclusion is further strengthened by the finding that unlike tetraethylammonium, 4-aminopyridine induces bursts of release, presumably by producing multiple action potentials in the nerve terminal. Tetraethylammonium probably acts by blocking the delayed potassium conductance, but the blockade of Ca2+-activated K+ conductance cannot be excluded. 4-Aminopyridine, however, probably blocks the fast inactivating (IA) K+ current, but it also may be acting directly on the voltage-dependent Ca2+ conductance or on the intracellular Ca2+ buffering. PMID- 2887266 TI - [Benign adrenal pheochromocytoma in adults]. PMID- 2887268 TI - Pretreatment of human platelet membranes with trypsin abolishes GTP but not Na+ effects on alpha 2-adrenoreceptor-agonist interactions. AB - The affinity of many types of membrane-bound receptors coupled negatively to adenylate cyclase is regulated by divalent and monovalent cations and by guanine nucleotides (GTP). We used alpha 2-adrenoreceptors of human platelets as a model system to find out the effect of limited proteolysis with trypsin on the regulation of the alpha 2-adrenoreceptor-agonist interactions by GTP and Na+. We found that partial proteolysis of the membranes with trypsin for 3 min at 35 degrees C reduced specific [3H]yohimbine binding to platelet membranes to 40-50% of control. The following characteristics of the receptors remaining after proteolysis were similar to those of untreated membranes: affinity for the agonist and antagonists, stereospecificity, and kinetic properties. Trypsin also did not modify the ability of the receptor's change from a high to low affinity state in the presence of Na+. These findings suggested that the capability of the receptors to recognize the ligand and their ability to undergo a conformational change in the presence of the agonist were retained despite a reduction in the total number of receptors by trypsin. However, the modulation of the receptor- agonist interactions by GTP or Mg2+ was lost in the trypsin-pretreated membranes, while the modulation by Na+ remained intact. It is suggested that the loss of GTP or Mg2+ effects on receptor--ligand interactions produced by trypsin may be due to trypsin-induced disruption of subunits (alpha i, beta gamma) interactions of Gi protein. PMID- 2887269 TI - Nonadrenergic modulation by clonidine of the cosecretion of catecholamines and enkephalins in adrenal chromaffin cells. AB - Cultured bovine chromaffin cells cosecrete catecholamines and enkephalins following cholinergic nicotinic stimulation. Initial reports on the inhibitory effect of clonidine on catecholamine secretion raised the possibility of a modulation of chromaffin cell function through a presynaptic adrenergic mechanism. The purpose of this work was to investigate the pharmacological characteristics of this inhibitory effect of clonidine on the cosecretion of catecholamines and enkephalins in 4-day-old cultured chromaffin cells. We observed that clonidine completely inhibits nicotine-stimulated secretion of both leucine-enkephalin and catecholamines with an IC50 of 34 microM. Treatment of chromaffin cells for 3 days with 100 nM reserpine leads to a 67% increase in nicotine-stimulated secretion of leucine-enkephalin without any effect on the IC50 of clonidine. In reserpine-treated chromaffin cells, norepinephrine (100 microM) inhibits only by 27% nicotine-stimulated secretion of leucine-enkephalin with an IC50 of 50 microM. Neither the alpha 2-adrenergic antagonist yohimbine nor the alpha 1-adrenergic antagonist prazosin could fully reverse the inhibitory effect of clonidine on leucine-enkephalin secretion at 10 nM. These results tend to rule out the role of alpha-adrenergic receptors in the mediation of clonidine inhibition of cosecretion in chromaffin cells. PMID- 2887270 TI - Acute effects of ethanol on baroreceptor reflex control of heart rate and on pressor and depressor responsiveness in rats. AB - In rats anesthetized with alpha-chloralose, doses of 0.1, 0.5, and 1 g/kg of ethanol produced an upward shift of baroreflex curves constructed by plotting the heart rate response against mean arterial pressure following evoked rises in mean arterial pressures by phenylephrine or angiotensin II. Whereas the upward shift of baroreceptor curves may be related, at least in part, to a higher base-line heart rate after ethanol, the data showed that the 1 g/kg dose of ethanol significantly depressed baroreflex sensitivity, suggesting that higher doses of ethanol impair baroreflex-mediated bradycardia. The phenylephrine, but not the angiotensin II or the nitroprusside, dose-response curves were shifted to the right after ethanol, indicating a decreased pressor responsiveness and suggesting that ethanol may have alpha-adrenergic blocking activity. This effect was also obtained in conscious rats. That this effect was not influenced by changes in baroreflex sensitivity was supported by the finding that a similar shift of the phenylephrine pressor-response curve was obtained in bilaterally vagotomized and hexamethonium-treated rats. Whether this effect of ethanol on baroreflex control of heart rate was influenced by anesthesia was investigated in conscious rats; the 1 g/kg dose of ethanol that produced the most significant decrease in baroreflex sensitivity was used in these experiments. Ethanol was still able to significantly inhibit baroreflex sensitivity in conscious rats, but the upward shift of the baroreflex curve and the elevated base-line heart rate no longer occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887271 TI - The roles of monoaminergic neurotransmitters in thermoregulation. AB - Recent studies of the organization of the thermoregulatory system and evaluation of experimental evidence from electrophysiological, neuropharmacological, and neuroanatomical studies suggest that the monoamines noradrenaline and 5 hydroxytryptamine are involved in modulations of thermoregulation rather than in thermoregulation per se: they do not seem to transfer specific thermal information but rather modulate the signals passing from thermosensors to thermoregulatory effectors. Theoretically, the central monoamines could be modulating the input from thermosensors, or the central integration of thermal signals, or the outflow of signals to thermoregulatory effectors. The modulatory action of the monoamines on thermosensitive and thermointegrative hypothalamic neurons is best documented. There, the monoamines 5-hydroxytryptamine and noradrenaline seem to act as antagonists, which enhance or diminish the effects of thermal afferents mediated by other transmitters. Moreover, the antagonistic monoaminergic systems are apparently interconnected and can influence each other at a lower brain stem level. The activity in central monoaminergic systems can also be modified by neurohumoral feedback mechanisms from the periphery. By means of these interrelations the vegetative responses of the organism can be corrected and optimized. PMID- 2887272 TI - Bacillus subtilis Lyt+ and Lyt- strains secrete peptidoglycan hydrolases. AB - The phenotypes characteristic of the pleiotropic lytic-deficient Bacillus subtilis mutants have been attributed to reductions in N-acetyl-muramoyl-L alanine amidase (EC 3.5.1.28) and endo-beta-N-acetyl-glucosaminidase (EC 3.2.1.30). It is reported here that these peptidoglycan hydrolases are secreted. The FJ3 (lyt-1), FJ6 (lyt-2), and Ni15 (lyt-15) mutants secreted the enzymes in amounts comparable to a Lyt+ strain. Thus, the Lyt- mutants appear not be as deficient in the enzymes' synthesis as their cell-bound activities indicated. Based on the levels of cell-bound and extracellular activities measured during growth, it is suggested that the Lyt- phenotype may be due to a deficiency of the enzymes' acceptor(s) in cell walls. PMID- 2887274 TI - Beta-blocker therapy and the risk of anaphylaxis. PMID- 2887273 TI - Wall turnover deficiency of Bacillus subtilis Ni15 is due to a decrease in teichoic acid. AB - Bacillus subtilis Ni15 is deficient in cell wall turnover. The deficiency is removed if the medium contains 0.2 M NaCl, which does not affect growth. The levels of amidase and glucosaminidase, the most likely enzymes involved in turnover, were, in stationary phase Ni15 cells, similar to those in late exponential phase cells of a standard strain. The Ni15 enzymes were not salt sensitive. However, the Ni15 walls contained 4.7-fold less phosphorus than the walls of the standard strain. Since the phosphorus content of B. subtilis walls reflects the level of teichoic acid, it is proposed that the turnover deficiency of this strain is due to a decrease in wall teichoic acid. PMID- 2887275 TI - Human T-cell leukemia virus type I infection in hemodialysis patients. AB - Human T-cell leukemia virus Type I (HTLV-I) has been detected in a high proportion of individuals in Kumamoto prefecture (Kyushu) and Okinawa, where adult T-cell leukemia (ATL) is more likely to occur. The seroprevalence of antibody to HTLV-I was evaluated in hemodialysis patients and healthy individuals in the ATL endemic area. The prevalence of antibody to HTLV-I in 13,329 healthy controls was 3.6%, compared with 19.7% in 949 chronic hemodialysis patients. The prevalence of hemodialysis patients was significantly higher (P less than 0.01) than that in healthy individuals. Of 681 blood transfused patients who had undergone hemodialysis, 153 (22.5%) were seropositive, compared with 34 (12.7%) of the 268 who had not received the blood transfusion. The incidence was higher in dialysis patients who had been transfused than in those who had never received blood transfusions. Immune defects associated with uremia may have predisposed the patients to HTLV-I infection. Repeated antigenic stimulation from multiple infectious agents may have also played a role. The findings suggest an association between maintenance hemodialysis and HTLV-I infection, which can not be explained solely by blood or blood products. PMID- 2887276 TI - The occurrence of catecholamine neurons in a parietal lobe ganglioglioma. AB - A parietal lobe ganglioglioma in a 2-year-old girl was investigated ultrastructurally and immunohistochemically, using antiserum against tyrosine hydroxylase (TH), a rate-limiting enzyme of the catecholamine (CA)-synthesizing pathway. The tumor was composed essentially of neuronal and astrocytic cells. Ultrastructurally, numerous dense core vesicles measuring between 56 nm and 136 nm (mean, 90 nm) in diameter were observed in the neuronal cytoplasm and processes. The fact that the TH immunohistochemistry revealed many positive neuronal cells in the tumor tissue was of considerable interest. The implications and possible significance of the presence of CA neurons in this ganglioglioma are discussed. PMID- 2887278 TI - Loss of one chromosome #13 during development of a polyposis tumor. AB - A cell panel from six different familial cancers, where both normal and tumor tissues were available, was examined for genotypic changes with polymorphic DNA probes. Seventeen probes were tested, representing chromosomes #1, #2, #5, #6, #13, #14, #17, and #19. One probe, p7F12 (D13S1, at 13q12-q14) revealed loss of heterozygosity in two tumors: an osteosarcoma from a patient with retinoblastoma that had been included as a control, and one polyposis tumor that had been established in nude mice from a duodenal carcinoma biopsy. Loss of heterozygosity was observed in the first passage of the mouse tumor. Chromosome analysis in later passages revealed loss of one whole chromosome #13 as the single consistent karyotypic change. PMID- 2887279 TI - Demonstration of in vivo formation of the nitrosamine N-nitroso-N-methylaniline from amyl nitrite. AB - Kaposi's sarcoma is associated with Acquired Immune Deficiency Syndrome (AIDS) in U.S. homosexuals. A possible explanation is that butyl nitrite, inhaled as a drug of abuse, initiates the tumor via the in vivo formation of N-nitroso compounds. To demonstrate that such a process can occur, we injected mice i.p. with the amine N-methylaniline (250 mg/kg), gavaged them 30 min later with amyl nitrite (AmNO2, 40 mg/kg), killed the mice after another 30 or 60 min, and analyzed the carcasses for N-nitroso-N-methylaniline (NMA). We obtained 480 +/- 130 (mean +/- S.E. for 6 mice killed after 30 min) and 380 +/- 40 (for 6 mice killed after 60 min) nmol NMA/mouse. Much lower yields were obtained when AmNO2 was injected i.p. and methylaniline was gavaged. Hence, relatively large amounts of at least one nitrosamine can be produced in vivo from simple nitrite esters. PMID- 2887277 TI - Cytogenetic studies of individuals from four kindreds with multiple endocrine neoplasia type II syndrome. AB - Multiple endocrine neoplasia type II (MEN-II) syndrome is an autosomal dominant condition characterized by medullary carcinoma of the thyroid, pheochromocytoma, and parathyroid adenoma. A cytogenetic investigation was conducted on 13 MEN-II syndrome patients from four unrelated kindreds and 13 age-matched control subjects for chromosome instability and the chromosome 20 deletion reported in MEN-II syndrome. A significant increase (p less than 0.05) was found in the total number of chromatid and chromosome aberrations in MEN-II cells (12.3%) compared with control cells (6.9%) grown at 96 hours in mitomycin C (20 ng/ml, final concentration). The major difference between the two groups was in chromatid, and not chromosome, aberrations. There was no difference between MEN-II and control individuals in fragile site expression, the number of sister chromatid exchanges or cell kinetics. A blind analysis of high-resolution G-banded chromosomes was performed on blood specimens from 13 MEN-II and seven control individuals. Twelve of 13 MEN-II patients and one of seven control subjects were scored as having a 20p12.2 deletion (chi 2 = 12.6; p less than 0.001). Additional research is needed to determine if this cytogenetic finding is due to a chromosome deletion, inversion, or polymorphism. PMID- 2887281 TI - Transforming growth factor alpha and beta expression in human colon cancer lines: implications for an autocrine model. AB - Three human colon cancer lines (SW480, SW620, WIDR) secrete different levels of transforming growth factor beta (TGF beta)-like and transforming growth factor alpha (TGF alpha)/epidermal growth factor (EGF)-like molecules into serum-free conditioned media as measured by competing activity in TGF beta and EGF radioreceptor assays. SW480 cells, the highest producers of TGF beta-like activity, lack detectable TGF beta receptors while SW620 cells, the highest producers of TGF alpha/EGF-like activity, lack EGF receptors. This study investigated the production of these growth factors at the mRNA level and examined the mechanism of loss of detectable receptors. Using complementary DNA probes for TGF beta and TGF alpha, it was demonstrated that mRNA levels correlated with the amounts of TGF beta and TGF alpha produced; TGF beta gene expression was highest in SW480 cells and TGF alpha gene expression was highest in SW620 cells. Acid washing of the SW480 cells prior to performing the TGF beta binding assay resulted in the unmasking of substantial levels of TGF beta receptors. Neither acid washing nor preincubation with suramin uncovered EGF receptors in SW620 cells. Also, and in contrast to the other two lines, EGF receptor expression could not be detected in SW620 cells by Northern gel analysis of receptor messenger RNA or by immunological analysis of receptor protein. Thus two distinct mechanisms (occupation of TGF beta receptor in SW480 cells, or absence of EGF receptor in SW620 cells) explain the lack of detectable TGF beta and EGF receptors in the binding assays. The autocrine hypothesis remains viable for TGF beta in SW480 cells but not for TGF alpha in SW620 cells; this would not discount a paracrine role in this latter case. PMID- 2887280 TI - Purification and characterization of a novel transforming growth factor. AB - Previous studies have indicated that an autostimulatory transforming growth factor was required for the optimal growth of SW-13 adrenal carcinoma cells in soft agar. The production of SW-13 colony-stimulating activity by other human malignant cell lines of both epithelial and mesenchymal origin has been demonstrated. Evidence was presented indicating that the stimulating activity detected in crude acid-ethanol extracts was an acid- and heat-stable polypeptide requiring disulfide bonds for full activity. This activity was detected more frequently in tumors and human cancer cells in culture of epithelial origin than of mesenchymal origin and in a variety of nonneoplastic tissues. In the present study, this activity, termed epithelial transforming growth factor (TGFe) because of its ability to stimulate soft agar growth of certain epithelial cells, was partially purified from bovine kidney. Fourfold purification of the kidney acid ethanol extract with 50% maximal growth-stimulatory activity of 10 micrograms was achieved using molecular sieve chromatography where TGFe eluted with an apparent molecular weight of 20,000-25,000. The next purification step, molecular sieve high performance liquid chromatography, yielded a 50% maximal growth-stimulatory activity of 50 ng and an 800-fold purification from the initial acid-ethanol extract. TGFe eluted in the Mr 11,000 range. Reversed phase high performance liquid chromatography with a C18 column was then used, yielding a single or double peak of SW-13 colony-stimulating activity at 30-35% acetonitrile. The degree of purification was 11,000-fold with a 50% maximal growth-stimulatory activity of 3.5 ng. Analysis of the peak on 12.5% sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed a major and sometimes single band with a molecular weight of 23,000-25,000. Extraction of protein from the polyacrylamide gel demonstrated that only the Mr 23,000-25,000 band stimulated soft agar growth of SW-13 cells. The biological activity of the partially purified TGFe was found to differ from other known growth factors with regard to its ability to stimulate soft agar growth of SW-13 cells with the exception of basic fibroblast growth factor (FGF). The acid lability of FGF, the different molecular weights of these two growth factors, the lack of stimulation of soft agar growth of A431 cells, and the lack of binding of TGFe to FGF receptors indicated that TGFe was not related to basic FGF. Partially purified TGFe was also found to stimulate soft agar growth of two squamous cell carcinoma lines, A431 and D562, and the mouse embryo-derived AKR-2B cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2887282 TI - Heterologous regulation of the epidermal growth factor receptor by palytoxin, a non-12-O-tetradecanoylphorbol-13-acetate-type tumor promoter. AB - Previous results have established that 12-O-tetradecanoylphorbol-13-acetate (TPA) type tumor promoters can alter the properties of the epidermal growth factor (EGF) receptor through activation of protein kinase C. In order to determine whether other, non-TPA-type tumor promoters might similarly influence growth mediating receptors, we investigated the effect of palytoxin on EGF binding in Swiss 3T3 fibroblasts and human epidermal carcinoma (A431) cells. In both cell types, pretreatment with a low dose of palytoxin (1-11 pM) at 37 degrees C causes a decrease in EGF binding. In Swiss 3T3 cells the inhibitory effect is temperature dependent and does not occur at 4 degrees C, indicating that palytoxin is not directly competing with EGF for binding. As assessed by effects on DNA synthesis, palytoxin is not toxic at these concentrations and does not appear to be mitogenic for these cells. Although palytoxin, like phorbol esters, alters EGF binding, its action in Swiss 3T3 cells differs from that of TPA-type tumor promoters in at least 4 respects: (a) the kinetics and dose dependence differ significantly from that of phorbol dibutyrate; (b) the effect is not readily reversible; (c) there is loss of low-affinity as well as high-affinity binding sites; (d) the effect is independent of cellular protein kinase C levels. These results indicate that palytoxin is capable of heterologous regulation of the EGF receptor through a novel mechanism and suggest that certain non-TPA-type tumor promoters as well as TPA-type tumor promoters may act in part through modulation of growth regulatory pathways. PMID- 2887283 TI - Clonal analysis using recombinant DNA probes from the X-chromosome. AB - It has been demonstrated that restriction fragment length polymorphisms of X chromosome genes can be used in conjunction with methylation patterns to determine the clonal composition of human tumors. In this report, we show that several X-chromosome probes can be used for such analyses. In particular, probes derived from the hypoxanthine phosphoribosyltransferase gene and the phosphoglycerate kinase gene could be used for clonal analysis in over 50% of American females. The X-inactivation patterns observed with these probes were found to accurately reflect clonality in more than 95% of 92 tumors tested. PMID- 2887284 TI - Metabolic basis for the protective effect of the antioxidant ethoxyquin on aflatoxin B1 hepatocarcinogenesis in the rat. AB - The effect of dietary administration of 0.5% ethoxyquin (EQ) on the in vivo induction of enzymes and effect on aflatoxin B1 (AFB1)-DNA binding in liver and the consequent in vitro metabolism of AFB1 by male Fischer F344 rat liver-derived fractions have been examined. EQ increased microsomal cytochrome P-450s, in particular those isozymes classed as phenobarbital inducible, and the in vitro rate of metabolism of AFB1. The formation of the presumed detoxified metabolites, aflatoxins M1 and Q1, was enhanced to a greater extent than was the formation of the active metabolite, aflatoxin B1-8,9 epoxide (assessed by the level of aflatoxin B1-8,9-dihydrodiol). Prolonged feeding with EQ was accompanied eventually by a reduction in the initially elevated cytochrome P-450 content, but this was not reflected in any significant decrease in the rate of AFB1 metabolism in vitro. EQ increased the glutathione S-transferase activity of the liver cytosol fractions as assessed with the model substrate 1-chloro-2,4 dinitrobenzene. The capacity of these fractions specifically to catalyze the conjugation of AFB1 with glutathione was induced to a far greater extent than was the conjugation of 1-chloro-2,4-dinitrobenzene. gamma-Glutamyl transpeptidase was induced in the periportal areas of the liver lobule. Reduced in vivo binding of [3H]AFB1 to DNA of liver and kidney was found to result from EQ treatment. It is concluded that the reduced hepatocarcinogenesis which results from feeding EQ simultaneously with AFB1 is due to the reduction in DNA-adduct formation which in turn is due at least in part to increased detoxifying metabolism in the microsomal, cytosolic, and plasma membrane compartments of the liver cells. PMID- 2887286 TI - Revascularization of the ischemic myocardium: current results and expectations for the future. PMID- 2887285 TI - [Effect of the stimulation and inhibition of beta adrenergic receptors on the contractile function and regional myocardial perfusion]. PMID- 2887287 TI - Overview of completed sudden death trials: European experience. AB - Progress in understanding the epidemiology and mechanism of sudden cardiac death (SCD) has been rapid over the past two decades. This, together with the availability of drugs with actions that potentially may counter the pathophysiology of sudden death, has led to myriad trials aimed at prolonging life for high-risk individuals. European countries have contributed a major share both to the development of these drugs and to subsequent tests of their efficacy. Ventricular fibrillation (VF), either unheralded or secondary to fresh myocardial ischemia, is by far the most common cause of SCD. The classes of drugs with profiles that might be expected to influence the occurrence of VF directly are antiarrhythmics, calcium channel blockers, platelet-active agents, and beta adrenoceptor antagonists. Twenty-four of the European trials that employed agents from these groups have special significance because of their design and size. Studies of two of the calcium channel blockers have not demonstrated any life saving potential to date. One platelet-active agent - aspirin - has shown favorable trends. Results with the use of antiarrhythmic agents have been disappointing, probably because their adverse effects, including arrhythmogenesis in some patients, have countered the antiarrhythmic effects that other patients have achieved. Nevertheless, evidence suggests that lidocaine can reduce the incidence of VF; this can reasonably be equated with life-saving potential whenever defibrillation is not available. Trials with beta-blocking drugs have been the most encouraging; seven of the 11 trials that have been considered demonstrated a significant reduction in sudden death, which was variously defined, and a strong trend toward reduction was observed with another. None of the trials showed an unfavorable trend. The results of completed trials now offer practical guidance to physicians with responsibility for the care of patients with ischemic heart disease, especially those who have features that indicate high risk. PMID- 2887289 TI - Somatostatin-like immunoreactivity in human sympathetic ganglia. AB - The localization of somatostatin-like immunoreactivity (SOM-LI) was examined in human lumbar sympathetic ganglia using the peroxidase-antiperoxidase method. Few of the principal neurons showed immunolabelling for somatostatin and sparse networks of nerve terminals were unevenly associated with ganglion cells. Using light microscopy, the most intense SOM-LI was seen in the perinuclear zone of the neurons. Electron-microscopically, the staining was localized on the membranes of the Golgi apparatuses. In the nerve terminals, SOM-LI was seen inside the small vesicles (40-60 nm diameter). All neurons with SOM-LI were also found to be tyrosine-hydroxylase immunoreactive when examined with a double-staining technique. These results provide evidence that somatostatin and noradrenaline co exist in human sympathetic neurons. PMID- 2887288 TI - Overview of completed sudden death trials: US experience. AB - Ventricular arrhythmias are the major cause of death in patients with coronary heart disease. By suppressing the arrhythmias, antiarrhythmic agents have the theoretical potential of preventing sudden arrhythmic deaths. A large number of randomized, controlled clinical trials of these agents have been conducted during the early hospital phase after an acute myocardial infarction as well as after discharge. Included in this review are approximately 20 mortality trials of antiarrhythmic drugs, including beta blockers, which have been conducted in the United States and Australia. Results of the trials of antiarrhythmics reported to date have not demonstrated an effect on patient survival or risk of sudden death. Three possible explanations exist. First, these agents do not improve prognosis, which is contrary to massive evidence from animal, clinical, and epidemiologic studies. Second, drug treatment prolongs life, but benefit has not been observed in the trials. This explanation is plausible, since the completed trials have methodologic limitations. Third, control of ventricular arrhythmias helps some patients but harms others. Larger, properly designed trials are needed to resolve the uncertainty about the value of antiarrhythmics in the prevention of sudden death. The short- and long-term trials of beta blockers have documented an effect on survival. The benefit seems to be explained primarily through a reduction in sudden or instantaneous death. Whether this effect is mediated through a reduction in ventricular ectopies or an elevation of the fibrillation threshold is debated, as is the effect, if any, of beta-2 blockade on the incidence of ventricular fibrillation. PMID- 2887290 TI - Immunoreactivity for calcitonin gene-related peptide in neuroepithelial bodies of the newborn cat. AB - Immunoreactivity for calcitonin gene-related peptide is demonstrated for the first time in neuroepithelial bodies in the lung of newborn cats after Bouin fixation and embedding in paraffin. The intense staining clearly identifies these bodies at the level of bronchioli and alveoli. Occasionally, single neuroepithelial endocrine cells, displaying immunoreactivity for calcitonin gene related peptide are observed. In the kitten lung, identification and localization of neuroepithelial bodies after immunocytochemical staining for calcitonin gene related peptide are superior to the analysis based on other techniques, i.e., the argyrophilic reaction, periodic acid Schiff-lead hematoxylin method, and immunocytochemical staining for serotonin. The serial-section technique revealed that in neuroepithelial bodies of the newborn kitten lung, immunoreactivity for calcitonin gene-related peptide coexists with immunoreactivity for serotonin in individual cells. The functional significance of the calcitonin gene-related peptide in neuroepithelial bodies remains to be elucidated. PMID- 2887291 TI - [Study on the spread of hemorrhagic fever with renal syndrome among animal hosts]. PMID- 2887292 TI - [Interference of suspension in water on the effect of biological insecticides on mosquito larvae]. PMID- 2887293 TI - Regulation and function of the Drosophila segmentation gene fushi tarazu. AB - The Drosophila segmentation gene fushi tarazu (ftz) is expressed in a pattern of seven stripes at the blastoderm stage. Two cis-acting control elements are required for this expression: the zebra element, which confers the striped pattern by mediating the effects of a subset of segmentation genes; and the upstream element, an enhancer element requiring ftz+ activity for its action. Fusion of the upstream element to a basal promoter results in activation of the heterologous promoter in a ftz-dependent striped pattern, supporting the idea that ftz regulates itself by acting through its enhancer. The upstream element can also confer expression patterns similar to that of the homeotic gene Antennapedia, suggesting that a similar element may play a role in the activation of Antennapedia. PMID- 2887294 TI - Camptothecin-induced in vivo topoisomerase I cleavages in the transcriptionally active tyrosine aminotransferase gene. AB - The topoisomerase I inhibitor camptothecin induces the formation of covalent topoisomerase I-DNA intermediates in vitro. In vivo these intermediates are produced upon administration of camptothecin to FTO-2B cells, as demonstrated by the occurrence of single-stranded DNA breakages that have protein covalently associated with the free 3' end and by the covalent association of approximately 50% of nuclear topoisomerase I with DNA. We have analyzed the frequency and distribution of camptothecin-induced topoisomerase I strand cleavages in the transcriptionally active rat tyrosine aminotransferase gene. Cleavages are largely confined to the transcribed region and occur predominantly on the lower strand. Increasing the transcriptional activity of the gene with either glucocorticoids or cAMP increases the intensity but does not change the position of camptothecin-induced cleavages. Camptothecin treatment decreases tyrosine aminotransferase mRNA levels and inhibits transcription. These observations suggest that topoisomerase I participates in transcriptional elongation. PMID- 2887295 TI - Human muscle neural cell adhesion molecule (N-CAM): identification of a muscle specific sequence in the extracellular domain. AB - cDNA clones encoding neural cell adhesion molecule (N-CAM) mRNAs of 6.7, 5.2, and 4.3 kb from human skeletal muscle cells were isolated. A 6.7 kb mRNA encodes a transmembrane N-CAM isoform, present predominantly in mononucleate myoblasts, that shows sequence homology with chick brain N-CAM-140 and is down-regulated during myotube formation. In contrast, the 5.2 and 4.3 kb mRNAs encode nontransmembrane N-CAM isoforms that greatly increase during myoblast fusion. Furthermore, a discrete muscle-specific sequence domain (MSD1) was detected in the extracellular coding regions of the 5.2 and 4.3 kb mRNAs. This encodes a unique run of 37 amino acids and is not expressed in 7.2 and 6.7 kb mRNAs from human or chick brain or in the corresponding 6.7 kb muscle transcript. The MSD1 is also absent from chick and mouse brain mRNAs of 4.0 and 2.9 kb. These results show that diversity in N-CAM primary structure can be found in the extracellular domain in a tissue-specific manner. PMID- 2887296 TI - Deterioration of cellular immunity during aging. The relationship between age dependent impairment of delayed-type hypersensitivity reactivity, interleukin-2 production capacity, and frequency of Thy-1+,Lyt-2- cells in C57BL/Ka and CBA/Rij mice. AB - The effect of aging on the delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) in vivo and the interleukin-2 (IL-2) production capacity in vitro by spleen cells from young (17 weeks) and old (125 weeks) CBA/Rij and C57BL/Ka mice were investigated. For both CBA/Rij and C57BL/Ka mice an age-related decline in the DTH response to SRBC and the IL-2 production capacity was observed. Both parameters are mediated by Thy-1+,Lyt-2- spleen cells. For both mouse strains the proportion of Thy-1+,Lyt-2- spleen cells declined less strongly with aging than the DTH reactivity and the IL-2 production capacity. From this it was concluded that not only a quantitative but also a qualitative decrease of T-cell function occurs during senescence. It was also investigated whether the proportion of Thy 1+,Lyt-2- peripheral blood lymphocytes can be used as a predictive value with regard to the decline of DTH with aging of the corresponding mouse. This was indeed found to be the case in CBA/Rij mice, but not in C57BL mice. PMID- 2887297 TI - Functional and biochemical characterization of B-cell differentiation factor (BCDF) produced by an HTLV-I-transformed human T-cell clone and demonstration of specific binding of the factor to a BCDF responsive cell line. AB - We have previously described YA2, a human T-cell clone that secretes B-cell differentiation factor (BCDF) but not B-cell growth factor (BCGF). The BCDFs secreted by YA2 and HTLV-I-transformed YA2 (TYA2) were functionally similar in their ability to stimulate Ig secretion by Staphylococcus aureus Cowan strain I activated B cells and IgM secretion by SKW6.4 cells. In addition, they were biochemically similar with a MW of 30 kDa by high-performance liquid chromatography (HPLC) sieving, and a pI of 6.0-6.8 by isoelectric focusing. The BCDF activity was not blocked by antibodies to interleukin 2 and BCGF. BCDF was purified from TYA2 supernatant by sequential media protein immunoadsorption, flat bed isoelectric focusing, HPLC TSK 2000 sieving, and repeated immunoadsorption and was then iodinated. The iodinated material had functional BCDF activity and migrated to a single band at MW 30 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and at pI of 6.8 by polyacrylamide gel isoelectric focusing. 125I-BCDF purified in this manner bound specifically to a BCDF-responsive cell line and not to phytohemagglutinin-activated T cells. 125I binding to the BCDF responsive cell line was competitively inhibitable by the addition of cold BCDF. Thus we have purified and characterized a factor with BCDF activity and demonstrated that this factor binds specifically to a BCDF-responsive cell line. PMID- 2887299 TI - Organizational fate of vimentin during redistribution of surface immunoglobulin in mouse splenic lymphocytes. AB - We have used immunofluorescence to examine the organizational fate of vimentin and its spatial relationship to the microtubule system during antibody-induced redistribution of surface immunoglobulin (sIg) in control and drug-treated mouse splenic lymphocytes. In control cells, vimentin is relocalized as a diffuse accumulation underneath the site of the cap during sIg redistribution. Observations on cells that were treated with colcemid or taxol prior to induction of sIg redistribution have further shown that vimentin accumulation corresponds to a dynamic rearrangement of this filamentous system which is related to, but is not required for, the energy-dependent translocation of sIg. PMID- 2887298 TI - An active T-cell-independent mechanism enhances MHC class I transcription and expression on a mouse T-cell lymphoma in vivo. AB - The present study focuses on the mechanism underlying changes in H-2 cell surface antigen expression after passage of the in vitro grown YAC-1 lymphoma as an ascites tumor. The increase in cell-surface expression correlated with elevated levels of class I transcripts as revealed by Northern blots. The enhanced H-2 expression was also seen with a cloned YAC-1 line, and not until 2 weeks after in vitro explantation had levels of H-2 decreased to those on the in vitro established YAC-1. Arguing for the necessity of a mature functioning immune system, suckling mice were unable to increase H-2 expression on inoculated lymphoma cells. Also pretreatment with cyclophosphamide or irradiation abolished the capacity of adult mice to increase cell surface H-2 on YAC-1 cells. A functioning T-cell system was not required for H-2 enhancement to occur since athymic nude mice were fully competent. The possible significance of an active T cell-independent host mechanism which enhances tumor H-2 expression at the transcriptional level is discussed. PMID- 2887300 TI - Effects of cytoskeletal inhibitors on water proton relaxation time changes in unfertilized and fertilized sea urchin eggs. AB - Unfertilized and fertilized sea urchin eggs were used for pulsed proton NMR spin lattice relaxation time (T1) measurements of cellular water. An 81% increase in T1 time at fertilization was largely explained by the accumulation of extracellular water in the perivitelline space. To assess the role of microtubule and actin filament assembly and disassembly, eggs were treated with drugs that are known to change these cytoskeletal elements (i.e., colchicine, taxol and cytochalasin B). Egg volume was also monitored in all studies to rule out the influence of water content changes on the observed T1 relaxation time changes. Neither assembly nor disassembly of microtubules changed the T1 relaxation time. The role of actin polymerization and depolymerization is discussed as a possible explanation for the observed cell cycle dependent water proton T1 relaxation time changes. PMID- 2887301 TI - Quantitative stereological evaluation of four histochemical markers of altered foci in multistage hepatocarcinogenesis in the rat. AB - Female F344/N rats dosed with diethylnitrosamine (DEN) 24 h after partial hepatectomy were treated with the promoting agents, phenobarbital (PB) or 3,4,7,8 tetrachlorodibenzo-p-dioxin (TCDD), or the peroxisome proliferating agent, WY 14,643, for 6 months. Another group was subjected to the Solt-Farber protocol. Altered hepatic foci (AHF) were analyzed by quantitative stereology from frozen serial sections stained for gamma-glutamyl transferase (GGT), canalicular adenosine triphosphatase (ATPase), glucose-6-phosphatase (G6Pase) and the placental isozyme of glutathione S-transferase (PGST). PGST scored more foci in all groups than GGT and ATPase. PGST marked greater focal volume than GGT or ATPase, and PGST marked focal volume equal to or greater than G6Pase in rats treated with PB, TCDD or the Solt-Farber protocol. However, after treatment with WY 14,643, GGT and PGST marked much less focal volume than ATPase or G6Pase, and PGST scored fewer foci than G6Pase. Numerical estimations of foci scored by those markers on the basis of area of the entire tissue section (per cm2) were relatively different from those values determined by quantitative stereology. While these results confirm earlier studies, they demonstrate the importance of quantitative stereologic analysis of AHF during multistage hepatocarcinogenesis. PMID- 2887303 TI - [Inhibition of tegumental gamma-glutamyltranspeptidase of Schistosoma japonicum by praziquantel]. PMID- 2887302 TI - Absence of gamma-glutamyl transpeptidase activity in neoplastic lesions induced in the liver of male F-344 rats by di-(2-ethylhexyl)phthalate, a peroxisome proliferator. AB - Male F-344 rats were fed a diet containing 2% di-(2-ethylhexyl)phthalate (DEHP) for 95 weeks. Liver nodules and/or hepatocellular carcinomas (HCC) developed in 6/10 rats fed DEHP and none were found in controls (P less than 0.005 by chi 2 test). All the nodules and HCC were negative for gamma-glutamyl transpeptidase. In the non-tumorous portions of liver, the hepatocytes contained an increased number of peroxisomes and extensive accumulation of lipofuscin. By immunocytochemical analysis, the liver peroxisomes in rats treated chronically with DEHP had visually detectable decrease in the H2O2-degrading catalase and increase in H2O2-producing fatty acyl-CoA oxidase. These results show that higher dietary level of DEHP, which causes substantially greater degree of peroxisome proliferation than the 1.2% dietary level used in the National Toxicology Program bioassay (1982, Publication no. NTP-80-37, Tech. Report Series No. 217), can induce liver tumors in male rats. PMID- 2887304 TI - Inhibitory effect of cetirizine 2HCl on eosinophil migration in vivo. AB - The effect of a potent antihistamine, cetirizine, was studied on allergic patients and normal subjects by means of an in-vivo 'skin window' technique. All subjects showed significant inhibition of skin-test responses to grass pollen, compound 48/80, histamine and methacholine, after administration of a single dose (10 mg) of cetirizine. Compared to placebo, cetirizine significantly decreased the eosinophils attraction at skin sites challenged with grass pollen and compound 48/80. In allergic patients no change in eosinophil migration pattern was noted with histamine and methacholine skin-tested sites. In normal subjects, compound 48/80 and histamine did not induce eosinophil accumulation and cetirizine did not modify cellular patterns as compared to placebo. These results suggest that cetirizine acts on eosinophil migration by inhibiting the release of mast cell mediators or inhibiting the eosinophilotactic mediators themselves. PMID- 2887305 TI - Glycylproline dipeptidyl aminopeptidase and gamma-glutamyl transpeptidase in human hepatic cancer and embryonal tissues. AB - Changes of glycylproline dipeptidyl aminopeptidase (GPDA) and gamma-glutamyl transpeptidase (gamma-GTP) activities and their subcellular distributions were compared in human hepatic cancer and embryonal tissues. The activity of GPDA in cancer tissues was significantly higher than that found in healthy liver, though there were no significant differences between fetal and adult livers. The placenta, however, had the highest GPDA activity. The activity of gamma-GTP, on the other hand, was increased significantly not only in cancer tissues but also in live tissues adjacent to the tumor, and it was higher in the fetal liver but much lower in the placenta. Subcellular distribution of GPDA was also different from that of gamma-GTP in cancer tissues, especially after postmortem changes. These results suggest the possibility that GPDA has carcinoembryonic characters similar to gamma-GTP, but the mechanisms, whereby serum activities of these two enzymes were increased in hepatocellular carcinoma patients, are different from each other. PMID- 2887306 TI - Protein-A purified human immunoglobulins: a comparison of thyroid stimulating and thyrotrophin receptor binding activities in thyrotoxicosis. AB - Protein-A purified human thyroid stimulating immunoglobulins (TSIg) and thyrotrophin binding inhibiting immunoglobulins (TBIIg) were measured in euthyroid subjects and thyrotoxic patients by bioassay and TSH radioligand receptor assay respectively. Unextracted sera from euthyroid and thyrotoxic subjects inhibited both basal and TSH stimulated iodide uptake in the bioassay, which was based on iodide uptake in porcine thyrocytes. Similar effects were seen with Ig and TSIg extracted from sera using either polyethylene glycol or ammonium sulphate. However IgG and TSIg prepared using Protein-A Sepharose CL-4B from sera of euthyroid subjects had little effect in this system. The majority of Protein-A purified TSIg preparations from sera of thyrotoxic patients stimulated iodide uptake in procine thyrocytes in a dose-dependent manner and most (85%) diluted parallel to both bovine and human TSH. TSIg and TBIIg from 73 patients with thyrotoxicosis were assessed using the bioassay and receptor assay and compared to a control group of 35 euthyroid subjects. The median (and range) values for TSIg and TBIIg in the euthyroid group were 4.35 (0.8 to 7.5, % stimulation over control) and 2.7 (-9.3 to 8.6, TBII index) for the bioassay and radioreceptor assay respectively. A value of greater than 10.0 in both assays was taken as a positive result. Of the thyrotoxic patients 61 out of 73 were positive in the bioassay (83.6%) compared to 60 in the radioreceptor assay (82.2%). There was a positive correlation between the two assays (r = 0.821, P less than 0.001). Of the 73 thyrotoxic patients 40 were untreated, 18 had received carbimazole and 15 had been previously treated with iodine-131. TSIg levels in the untreated thyrotoxics were similar to those in either group of treated patients. However they were higher (P less than 0.05) in the iodine-131 group than in the patients treated with carbimazole. Similar results were obtained for TBIIg. The coupling of a specific extraction method for human serum IgG with a bioassay for TSIg has demonstrated a high prevalence of these immunoglobulins in patients with thyrotoxicosis. The agreement between this assay and a radioreceptor assay was good, indicating that TSH displacing and thyroid stimulating activities of these immunoglobulins are closely related. PMID- 2887307 TI - Progress with the genetics of insulin-dependent diabetes mellitus. PMID- 2887308 TI - Changes in thyroid-stimulating and TSH-binding inhibitory activities in a patient who developed hyperthyroidism due to Graves' disease following primary hypothyroidism. AB - A 23-year-old female who developed thyrotoxic Graves' disease following primary hypothyroidism was reported. She presented with symptoms of hypothyroidism and slight exophthalmos. After primary hypothyroidism was confirmed, she was treated with T4 in a dose of 50 micrograms/d. Two months after delivery, 1 year after the initial diagnosis of hypothyroidism, hyperthyroidism developed while she was taking T4. Graves' disease was confirmed by persistent thyrotoxicosis, high 99mTc thyroidal uptake, negative T3 suppressibility and detection of TSH-receptor antibodies. During the hypothyroid phase, TSH-binding inhibitory immunoglobulins (TBII) could not be detected, while thyroid stimulating antibodies (TSAb) were positive showing between 5.8 and 9.0 fold increases in the amount of cAMP produced in cultured porcine thyroid cells. Her IgG did not inhibit TSH-induced cAMP increase in vitro. When she developed hyperthyroidism, TSAb activity became more potent (31.7 fold increase in cAMP) and TBII became positive (+61.3%). PMID- 2887309 TI - On the use of a new somatostatin analogue in the treatment of hypoglycaemia in patients with insulinoma. AB - A novel potent analogue of somatostatin, the octapepide SMS 201-995 was tested as a therapeutic manoeuvre to prevent hypoglycaemia in patients with insulinoma. We investigated the acute effects of a single 50 micrograms dose of the analogue administered s.c. in three patients, comparing the results in two of them with those obtained after administration of saline (control) and native somatostatin. In addition two patients were treated for up to 5 d with two or three daily s.c. injections (daily dose of analogue ranging from 100 to 300 micrograms). In two of the three patients SMS 201-995 suppressed circulating insulin levels by more than 50% and increased plasma glucose to hyperglycaemic levels for 6-8 h after a single injection. No undesirable effects of the administration of the analogue were observed. As opposed to insulin suppression obtained with native somatostatin, no rebound increase in insulin levels was observed after administration of the analogue. We conclude that SMS 201-995 prevented hypoglycaemia in two out of three patients with insulinoma. The advantage of s.c. administration, the long duration of action and the absence of a rebound phenomenon give this analogue a place in the pre-operative management of patients with insulinoma. PMID- 2887310 TI - Characteristics of patients with normal T3 and T4 and a low TSH response to TRH. AB - The nature of the thyroid disorder presented by patients with normal T4 and T3 but blunted TSH response to TRH has not been clarified. In this study, we compared thyroid function tests in 16 such patients with those of 14 controls and 10 hyperthyroid patients. Basal total T4, free T4, total T3, iodine uptake and cholesterol of the study group were similar to controls but significantly (P less than 0.001) lower than in hyperthyroid patients, except for cholesterol which was higher. In contrast, the basal TSH, increase in TSH after TRH stimulation, and decrease of T4 during T3 suppression tests were similar to data obtained in hyperthyroid patients but significantly (P less than 0.001) lower than in controls. Pulse rate was mid-way between the control and the hyperthyroid group. Thyroid stimulating antibody (TSAb) was measured with human thyroid cells in culture; the assay was positive in four subjects in the 16-patient group and in all hyperthyroid patients tested. TSH stimulation test showed a hyporesponse in iodine uptake in the four patients with positive TSAb (26 +/- 29%), as well as in hyperthyroid patients (6 + 5%). However, there was a hyper-response to TSH (213 +/- 52%) in the remaining 12 patients in the group, none of whom had TSAb. Thus TSAb is not seen as responsible for the thyroid disorder in the majority of patients with normal T3 and T4 and absent or blunted TSH response to TRH; surprisingly, most of these patients have thyroid hypersensitivity to TSH. These two characteristics, absence of TSAb and hypersensitivity to TSH, delineate a thyroid disorder clearly different from Graves' disease. PMID- 2887311 TI - Selective renal dopamine-1 receptor stimulation in man. AB - The selective dopamine-1 (DA-1) receptor agonist, fenoldopam, was studied during intravenous administration to ten normal male subjects on a diet of 150 mEq sodium and 60 mEq potassium per day to determine the mechanism of dopamine induced natriuresis. During DA-1 receptor stimulation, urine flow rate and renal plasma flow manifested a biphasic increase. Urine flow rate increased from a control of 13 +/- 1 to 17 +/- 1.2 ml/min and again to a peak of 16 +/- 1. Renal plasma flow increased from 344 +/- 39 to 481 +/- 44 ml/min and then to 497 +/- 38. Sodium excretion (UNaV) and fractional sodium excretion (FENa) demonstrated a sustained increase. UNaV rose from a control of 0.21 +/- 0.03 to 0.32 +/- 0.05 mEq/min. FENa rose from a control of 1.6 +/- 0.1 to 2.7 +/- 0.6%. Fenoldopam did not alter glomerular filtration rate. The association of changes in renal plasma flow and in UNaV and FENa demonstrate in man that DA-1 receptor stimulation causes natriuresis by direct renal tubular action. The renal tubular effect appears to be a major determinant of the degree of natriuresis. PMID- 2887312 TI - Biochemical and pharmacological characterization of ganglionic dopamine receptors. AB - The presence and the subtype of dopamine receptors in sympathetic ganglia were investigated. Using dopamine as well as preferential agonists and antagonists for the DA-1 and DA-2 receptor subtypes, we have studied dopamine receptors in both dog and rat sympathetic ganglia. Dopamine, fenoldopam, a DA-1 receptor agonist, and quinpirole, a DA-2 receptor agonist, caused significant inhibition of ganglionic transmission. The inhibitory action of quinpirole was selectively antagonized by the DA-2 receptor antagonist S-sulpiride but not by the DA-1 receptor antagonist R-sulpiride. In contrast, the inhibition of ganglionic transmission produced by fenoldopam was antagonized by R-sulpiride but not S sulpiride. The selective DA-1 receptor antagonist, SCH 23390 did not alter the inhibitory effect of fenoldopam at the ganglia. Dopamine and fenoldopam increased vascular but not ganglionic cyclic AMP. The increase in vascular cyclic AMP was antagonized by the DA-1 receptor antagonists SCH 23390 and R-sulpiride. Quinpirole caused a modest but significant decrease in ganglionic cyclic AMP, sensitive to blockade by S-sulpiride. These results show that dopamine and selective DA-1 and DA-2 receptor agonists inhibit ganglionic transmission by activating two distinct subtypes of dopamine receptors located on sympathetic ganglia. PMID- 2887313 TI - Hemodynamic effects of selective dopamine receptor agonists in the rat and dog. AB - The availability of highly selective dopamine receptor agonists has allowed the characterization of the role of DA1 and DA2 receptors in the cardiovascular system. Fenoldopam (SK&F 82526) is a potent agonist at DA1 receptors, with much less agonist activity at the DA2 subtype or at alpha and beta adrenoceptors. In contrast, SK&F 89124 activates only the DA2 subtype. SK&F 85174, the N-allyl derivative of fenoldopam, retains potent DA1 agonist activity but also has moderately potent agonist activity at the DA2 receptor. All three compounds will reduce blood pressure in hypertensive rats. In the anesthetized dog, each agonist will reduce blood pressure and total peripheral resistance. The overall hemodynamic profile is remarkably similar, despite the marked difference in dopamine receptor subtype selectivity. The principal pharmacologic difference is enhanced bradycardia with the compounds having DA2 agonist activity, resulting from activation of neuroinhibitory DA2 receptors on cardiac sympathetic nerve terminals. In the dog, each compound will increase renal blood flow. Studies in the anesthetized rat with fenoldopam and SK&F 89124, using radiolabelled microspheres to measure blood flow to various vascular beds, also show a significant increase in renal flow, with a tendency toward increased blood flow in the splenic and intestinal beds. Hence, dopamine receptor agonists offer a useful approach to cardiovascular therapy via DA1 mediated vascular dilation, DA2 mediated modulation of sympathetic tone or a combination of both activities. PMID- 2887314 TI - Identification and characterization of peripheral neuronal dopamine receptors in the rat. AB - The effects of local administration of the dopamine receptor agonists apomorphine and pergolide were investigated in the isolated autoperfused hindquarters, renal and superior mesenteric vascular beds of the rat, in order to assess whether presynaptic dopamine receptors in these vascular regions could play a role in the hypotensive effect of these agents. In the three vascular beds, local infusion of apomorphine and pergolide did not influence perfusion pressure per se, but clearly reduced the pressure response to electrical stimulation of the sympathetic innervation. Increases in perfusion pressure induced by local administration of noradrenaline were not influenced by apomorphine and pergolide. The inhibitory effect of apomorphine and pergolide on stimulation-evoked pressure responses was completely antagonized by the dopamine receptor antagonist haloperidol. The alpha 2-adrenoceptor antagonist rauwolscine, which completely blocked the inhibitory effect of the alpha 2-adrenoceptor agonist UK-14,304-18 on neurogenic vasoconstriction, had no influence on the inhibitory effect of apomorphine and pergolide. Like haloperidol, the DA2-receptor antagonist domperidone antagonized the inhibition of neurogenic vasoconstriction by apomorphine in the three vascular beds; the DA1-receptor antagonist SCH 23390 had no influence. These results indicate that inhibitory DA2-receptors are present on the sympathetic innervation to the hindquarters, renal and superior mesenteric vascular beds of the rat. PMID- 2887315 TI - Cardiovascular characterization of DA-1 and DA-2 dopamine receptor agonists in anesthetized rats. AB - This report summarizes studies aimed to characterize pharmacologically, hemodynamically and biochemically DA-1 (fenoldopam) and DA-2 (quinpirole) dopamine receptor agonists in anesthetized rats. Fenoldopam (20 micrograms/kg/min i.v. over 15 min) and quinpirole (10 micrograms/kg/min i.v. over 15 min) share the common property of decreasing mean carotid artery blood pressure by lowering peripheral vascular resistance. Fenoldopam increased mesenteric and renal blood flows whereas quinpirole decreased the former blood flow, but enhanced the latter. These effects of quinpirole were antagonized selectively by S-sulpiride, but not SCH 23390; however, with fenoldopam the reverse was found. In chlorisondamine-pretreated rats with blood pressure supported by vasopressin, fenoldopam, but not quinpirole, caused hypotension. In nephrectomized rats, the blood pressure effects of fenoldopam (assessed as area under the infusion time response curve) were more pronounced than in sham-operated controls. The hypotensive effects due to an i.v. bolus injection of fenoldopam, but not to acetylcholine, histamine, salbutamol or quinpirole, were significantly inhibited in rats pretreated with an infusion of fenoldopam. In pithed rats, quinpirole reduced the pressor responses to electrical stimulation of the spinal cord without affecting those to exogenous norepinephrine, angiotensin II or 5 hydroxytryptamine which, on the contrary, were inhibited by fenoldopam. The plasma renin activity (in intact rats) was reduced by quinpirole, but elevated by fenoldopam. The latter effect also occurred in pithed rats and was blocked by SCH 23390. Quinpirole lowered heart rate, whilst fenoldopam produced tachycardia. These effects of quinpirole and fenoldopam were significantly inhibited by S sulpiride and SCH 23390, respectively. In chlorisondamine-pretreated rats quinpirole failed to change heart rate whereas fenoldopam still increased it. In conclusion, these results indicate that DA-1 and DA-2 dopamine receptor agonists can be easily discriminated on the basis of their cardiovascular profiles. PMID- 2887316 TI - Pallister-Killian syndrome: cytogenetic and molecular studies. AB - Pallister-Killian syndrome is a dysmorphic syndrome characterized by a tissue limited mosaicism: a majority of fibroblasts have 47 chromosomes with an extra small metacentric chromosome, whereas the karyotype of lymphocytes is normal. In this study, the interpretation of the extra chromosome as composed of two short arms of chromosome 12 is confirmed, using molecular methods. Furthermore, restriction fragment length polymorphisms indicate that the two arms are identical, which is compatible with the hypothesis of an isochromosome 12p. A new feature which may be important in understanding the mechanism of origin of the abnormality is described: the proportion of abnormal mitoses falls dramatically during long-term culture of fibroblasts. PMID- 2887318 TI - Familial transmission of a ring chromosome 21. AB - A ring chromosome 21 was found in a phenotypically normal mother and her son. The clinical findings in the son were bilateral retention of the testes and a slightly delayed puberty onset. Consequences of a ring formation of a chromosome 21 in phenotypically normal patients are presented and discussed, and the previously reported cases of familially transmitted G-group ring chromosomes are reviewed. PMID- 2887317 TI - Carrier detection of haemophilia A using DNA markers in families with an isolated affected male. AB - The carrier status of women in five families with an isolated haemophilia male was assessed by pedigree analysis, coagulation factor assays and DNA markers. In three families, ten women could be given very low risks of being carriers based on DNA analysis. In two of the families the DNA markers identified the mutation as originating in either the maternal or maternal grandfather's germ cell. Combined DNA and coagulation data suggested that the affected male in a third family was a de novo mutation. DNA analysis of the affected male in another family identified a large deletion of the F8 gene which was present in his mother and three sisters, suggesting that the grandmother was a carrier. A combination of coagulation factor data and DNA marker assessment can determine the carrier status of the majority of females in families with isolated affected haemophilia A males. PMID- 2887319 TI - Evidence for a sperm mutation resulting in Duchenne muscular dystrophy. AB - DNA analysis of Xp21 markers in a family with two brothers affected with Duchenne muscular dystrophy (DMD) revealed that the mutation most likely had occurred in a grandpaternal sperm. There is therefore a low risk that the maternal aunts and their daughters are carriers of the DMD gene. PMID- 2887320 TI - X-linked retinoschisis is closely linked to DXS41 and DXS16 but not DXS85. AB - A linkage study was carried out in nine families with 24 males affected by X linked recessive retinoschisis (RS), using three polymorphic DNA probes from the distal segment of Xp. Close linkage of the disease locus with markers DXS41 (probe p99-6) and DXS16 (pXUT23) was found, confirming the location of the RS gene on the distal short arm of the X chromosome. Lod scores for linkage with DXS85 (probe 782) were negative. PMID- 2887321 TI - Pharmacological management of patients with peptic ulcer disease: prospects for the late 1980's. AB - Over the past ten years there have been major advances in the physician's ability to treat patients with peptic ulcer disease. Cimetidine continues to be the standard against which newer therapies are generally compared, although ranitidine is equally effective for short-term therapy, more effective for maintenance therapy, and has a superior safety profile. Famotidine is an even more potent H2 receptor antagonist, and initial clinical studies are promising. The initial concern for the development of gastric carcinoid lesions in rodents, maintained for long periods on high doses of omeprazole, defused the initial enthusiasm for this hydrogen-potassium ATPase "proton pump" inhibitor, but recent studies continue to show a marked efficacy of this agent for the short-term care of patients with gastric or duodenal ulcers and for the management of patients with the Zollinger-Ellison syndrome. Sulcrate continues to enjoy wide popularity for acute and chronic care of acid peptic disorders because of its local action and minimal adverse effects. Pirenzepine is effective in achieving and maintaining healing, but prevalence of anticholinergic side-effects has hampered enthusiasm for its widespread use. The 2 forerunners in the prostaglandin analogues arena, misoprostol and enprostil, are antisecretory agents when given in sufficiently high doses. These orally administered prostaglandins have a favourable safety profile, and their only adverse effect is that of the development of transient mild diarrhea. Finally, while antacids continue to be used in large amounts because of their over-the-counter availability, their clinical usefulness is limited by their unpalatable taste and the relatively large amounts usually required to achieve ulcer healing. PMID- 2887322 TI - Regulation of gastric acid secretion at the cellular level. AB - Gastric acid secretion is controlled by neurocrine, endocrine, and paracrine pathways. At the organ level, the neurocrine and endocrine systems provide long range regulation; and near the target cell the paracrine system appears to predominate. The integration of the regulatory commands from these various pathways is complex and, as a result, some pathways have not yet been clearly defined. Present evidence suggests that acetylcholine from mucosal nerve endings acts by 2 possible pathways. It interacts with muscarinic receptors on the oxyntic cell stimulating acid production. It is also capable of releasing histamine from the paracrine cell in the gastric glands, and histamine then acts on the oxyntic cells. The endocrine effect on acid secretion mediated by gastrin is less clear. Gastrin binds to oxyntic cell plasma membranes but has little or no direct stimulatory effect on the acid-secreting cell. It is assumed that its stimulatory action on acid secretion in vivo is mediated primarily by increasing histamine levels near the oxyntic cells. Histamine, released from paracrine cells near the oxyntic cells, is probably controlled by acetylcholine and gastrin, but other mechanisms are being explored. Histamine binds to the H2-receptors on the oxyntic cell plasma membrane, activating adenylate cyclase, which catalyzes the production of the intracellular messenger cyclic AMP. Cyclic AMP in turn activates a specific protein kinase, which phosphorylates a yet unknown substrate for the propagation of the stimulatory signal. The action of acetylcholine on the oxyntic cell receptors does not stimulate the production of cyclic AMP; instead, it acts on Ca++ channels, increasing the Ca++ entrance into the cell, which initiates the intracellular events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887324 TI - The clinical problem of stress ulcers. AB - True stress ulcers are primarily superficial gastric fundic lesions that occur in the clinical setting of severe shock, trauma, burns, and sepsis, especially peritonitis. They are to be clearly differentiated from Cushing's ulcers, exacerbation of pre-existent chronic ulcers, and drug-induced gastritis, all of which have completely different pathogenetic mechanisms. The etiology of true stress ulcers is most importantly related to ischemia and tissue acidosis, although luminal acid and pepsin are requisite for ulceration to occur. The sole clinical manifestation of stress ulcers is hemorrhage. Prophylaxis with antacids alone, or with a combination of antacids and H2 receptor antagonists is highly efficacious if luminal pH is carefully monitored. The treatment of exsanguinating hemorrhage, once established, carries with it an extremely high morbidity and mortality. PMID- 2887323 TI - Prostaglandins for duodenal ulcer. AB - Studies to date indicate that certain synthetic prostaglandin E derivatives, notably misoprostol and enprostil, possess duodenal ulcer healing efficacy that is equivalent to that of the existing H2-receptor antagonists. Whether healing is achieved by virtue of their antisecretory action alone or in combination with their cytoprotective properties cannot be ascertained. Earlier reports that non antisecretory prostaglandin E2 was effective for duodenal-ulcer healing suggested that cytoprotective mechanisms may contribute to ulcer healing, but this needs be confirmed. Chronic cigarette smoking adversely affects duodenal ulcer healing despite treatment with potent acid-reducing regimens. Evidence is available that cigarette smoking reduces luminal prostaglandins in the stomach, and that misoprostol, a prostaglandin E1 is able to overcome the adverse effect of smoking on duodenal ulcer healing, further suggesting that cytoprotective mechanisms may contribute to ulcer healing. Furthermore, misoprostol has been shown to be the first therapeutic agent capable of improving active chronic antral gastritis, which has recently been found to be almost invariably associated with active duodenal ulcer. PMID- 2887325 TI - Pharmacokinetics of bisoprolol during repeated oral administration to healthy volunteers and patients with kidney or liver disease. AB - The pharmacokinetics of bisoprolol were investigated following oral administration of 10mg once daily for 7 days in 8 healthy subjects, in 14 patients with different degrees of renal impairment and in 18 patients with liver disease. In healthy subjects peak and trough steady-state concentrations of 52 micrograms/L and 11 micrograms/L, respectively, an elimination half-life of 10.0 hours and total body clearance of 14.2 L/h were observed. 5.21 mg/24 hours of unchanged bisoprolol were recovered following urinary excretion during the dosage interval. In 11 patients with renal impairment (mean CLCR = 28 +/- 5 ml/min/1.72m2) half-life was prolonged to 18.5 hours, and peak and trough concentrations were 74 and 32 micrograms/L, respectively. Correspondingly, urinary excretion decreased to 3.35 mg/24 hours and total body clearance to 7.8 L/h. In uraemic patients (CLCR less than 5 ml/min/1.73m2) the total clearance of bisoprolol was 5.0 L/h and the elimination half-life was 24.2 hours. In patients with liver cirrhosis half-life increased to 13.5 hours, steady-state peak and trough concentrations increased to 62 and 22 micrograms/L, respectively, and total body clearance decreased to 10.8 L/h. The present study indicates that in patients with impairment of kidney or liver function accumulation of bisoprolol above a factor of 2 did not occur. However, in the terminal stages of insufficiency of kidney or liver function bisoprolol dosage should not exceed 10mg. PMID- 2887327 TI - Flumazenil in the management of acute drug overdosage with benzodiazepines and other agents. AB - A double-blind, randomized, placebo-controlled trial was employed to evaluate the place of flumazenil, a benzodiazepine antagonist, in the early management of 60 patients who went to an accident and emergency center with overdosage of sedatives. The level of consciousness was monitored by a modified Glasgow Coma Scale, and the response to the intravenous administration of up to 1 mg flumazenil or placebo was followed for periods between 1 and 24 hours. The increases in the glasgow coma scale at 5 minutes in the flumazenil-treated group were significant in the group as a whole (+4.9; P less than 0.005), in those who had taken benzodiazepines only (+5.3; P = 0.005), and in those with mixed overdosages (+5.6; P less than 0.005). There were no significant changes in the placebo-treated group. Some patients with overdosage with ethanol also responded to flumazenil, but there was no effect in patients with overdosage of barbiturates alone or tricyclic antidepressants. Flumazenil was well tolerated although three patients had mild withdrawal reactions. The need for intensive physiologic support was avoided in several cases, and the differential diagnosis of the unconscious patient was facilitated. PMID- 2887328 TI - The relative antihistaminic and psychomotor effects of hydroxyzine and cetirizine. AB - Twelve healthy subjects with atopy received single doses of hydroxyzine, 25 mg, its metabolite cetirizine, 10 and 20 mg, and placebo in a four-way crossover study randomized by Latin square design. Skin wheal response to histamine, psychomotor effects, and serum concentrations of each drug were measured for 36 hours after each dose. Central nervous system (CNS) effects were measured with critical flicker frequency, Stroop word testing, and visual analog scales. All three active treatments (cetirizine, 10 mg, cetirizine, 20 mg, and hydroxyzine) produced an equivalent suppression of skin wheal response to histamine that was significantly greater than placebo (P less than 0.01). Hydroxyzine produced a significant change compared with placebo in all three CNS parameters. Neither cetirizine, 10 mg, nor cetirizine, 20 mg, produced any significant change in CNS parameters. Both the intensity and time course of CNS effects were related significantly (P less than 0.05) to hydroxyzine concentrations. The CNS changes measured after oral hydroxyzine are the result of the parent drug, whereas its metabolite cetirizine when administered alone produced significant antihistaminic effects without CNS changes. PMID- 2887326 TI - Antipsychotic drugs. Clinical pharmacokinetics of potential candidates for plasma concentration monitoring. AB - Antipsychotic drugs (neuroleptics) are candidates for plasma concentration monitoring, but not all agents have the same potential in this respect. The present review analyses the available data on the kinetics and metabolism of fluphenazine, perphenazine, thiothixene, flupenthixol, clopenthixol, haloperidol, pimozide, penfluridol, sulpiride and clozapine. Although some of the drugs described in this review have been in use for many years, knowledge of their pharmacokinetics is still only approximate. This is primarily because determination in biological fluids is not always feasible. Accordingly, analytical methods useful for pharmacokinetic studies or plasma concentration monitoring of these antipsychotic drugs are discussed. With the exception of sulpiride, all the neuroleptics reviewed share some basic pharmacokinetic properties: good gastrointestinal absorption but reduced systemic availability because of hepatic first-pass metabolism, high hepatic clearance and a large apparent volume of distribution leading to an apparent elimination half-life of about 24 hours for most of these compounds. The renal elimination is negligible and it seems that these drugs do not possess active metabolites. The pharmacokinetic properties of antipsychotic drugs are important for the inclusion of a set of drugs in a psychiatric institution where there is a possibility of drug concentration monitoring. In addition, the availability of a depot preparation is of importance. These factors are discussed in view of the experience made during the last years in the University Psychiatric Institutions of Geneva. PMID- 2887330 TI - Lymphocyte transglutaminase function may be impaired in type 2 diabetes mellitus. AB - A method for capping of beta 2-microglobulin involving the transglutaminase inhibitor monodansylthiacadaverine was applied to lymphocytes from 17 patients with Type 2 diabetes mellitus and from a matched control group of 16 normoglycaemic healthy subjects. Monodansylthiacadaverine strongly inhibited the capping, which points to the involvement of transglutaminase in the redistribution of beta 2-microglobulin on the cell surface. The inhibition was more pronounced in lymphocytes from diabetic patients, indicating impaired transglutaminase function in Type 2 diabetes mellitus. PMID- 2887329 TI - Molecular mechanism of multidrug resistance in tumor cells. AB - The ability of tumor cells to develop simultaneous resistance to multiple lipophilic cytotoxic compounds represents a major problem in cancer chemotherapy. This review describes recent molecular biological studies which resulted in the identification and cloning of the gene responsible for multidrug resistance in human tumor cells. This gene, designated mdr1, is overexpressed in all and amplified in many of the multidrug-resistant cell lines analyzed. Gene transfer and expression assays have indicated that the mdr1 gene is both necessary and sufficient for multidrug resistance. The product of the mdr1 gene is P glycoprotein, a transmembrane protein which shares homology with several bacterial proteins involved in active membrane transport. P-glycoprotein appears to function as an energy-dependent efflux pump responsible for the removal of drugs from multidrug-resistant cells. The functions of the mdr system in normal cells and its potential clinical implications are discussed. PMID- 2887331 TI - Leucopenia in adult Still's disease during treatment with azathioprine and sulphasalazine. AB - The experience is reported concerning treatment of adult Still's disease with a combination of azathioprine and sulphasalazine. In three patients a favourable effect on the symptoms was noted. In one of these patients a year-long prednisone treatment was withdrawn and replaced by sulphasalazine. In all these cases, however, a decrease was seen in leucocyte counts to subnormal levels after the addition of sulphasalazine to a basis therapy with azathioprine 150-200 mg/d (2.1 3.3 mg/kg). The effect was only transitory in two patients, while it lasted several months in the third. In a fourth patient agranulocytosis developed after four days following the combined treatment with azathioprine 150 mg/d (2.3 mg/kg) and 250-1000 mg/d (4-15 mg/kg) of sulphasalazine, lasting four days before recovery. A later resumption of the combination therapy with these same drugs, but in a lower dosage, did not induce any acute changes in leucocyte counts. The skin rash provoked by sulphasalazine in two of the patients did not recur after desensitization. It is concluded, that this combination therapy is valuable in adult Still's disease, but that caution should be exerted during the initiation of sulphasalazine therapy. This should be monitored by daily measurements of leucocyte counts in the first weeks and preferably started by the use of a desensitising kit. PMID- 2887332 TI - Effect of beta 1-adrenoceptor blockade on plasma levels of atrial natriuretic peptide during exercise in normal man. AB - Increased plasma levels of atrial natriuretic peptide (ANP) during exercise have been reported. To investigate the role of tachycardia as a stimulus for release of ANP during exercise the following study was undertaken. Graded exercise was performed in six healthy volunteers before and after beta 1-adrenoceptor blockade. Plasma levels of ANP were determined at different workloads in both cases. At rest and at all workloads during exercise plasma levels of ANP were higher after beta 1-adrenoceptor blockade than without. Therefore, it is unlikely that tachycardia is a major stimulus for secretion of ANP during exercise. It is suggested that increased right atrial pressure and/or pulmonary arterial blood pressure and increased plasma levels of catecholamines are important secretory stimuli for ANP during exercise. PMID- 2887333 TI - Advances in the treatment of peptic ulcer disease. PMID- 2887334 TI - Therapy for asthma and allergic rhinitis. PMID- 2887335 TI - Occurrence of mannose resistant hemagglutinins in Escherichia coli strains isolated from porcine colibacillosis. AB - Three-hundred and fifty-eight E. coli strains isolated from piglets were tested for the presence of hemagglutinins by the use of the active hemagglutination test with or without mannose. Additionally 86 strains from the mentioned number of strains were investigated for the presence of common fimbriae using the same method but growing the strains in media especially suited for the development of this kind of fimbriae. These 358 strains and additionally 202 E. coli strains were tested using antisera for 987P and K88 antigens. It was found, using the active hemagglutination test, that 51.4% of the strains were hemagglutinating. The hemagglutinating strains carried the K88 antigen. All these strains were isolated from new-born and weaned piglets with enterotoxic form of colibacillosis, called also E. coli diarrhea. From cases of this form of colibacillosis originated also 26.7% of the strains in which common fimbriae (type 1) were detected. This result was obtained when the BHI medium was used for cultivation. In case of TSA medium only 2.3% of strains were positive. No specific or common fimbriae were found in strains recovered from septic form of colibacillosis and oedema disease (called also enterotoxaemic form of colibacillosis). No strain of 560 examined showed the presence of fimbrial 987P antigen. PMID- 2887336 TI - Freshwater or marine origin of the vertebrates? AB - 1. Paleontological data indicate that the earliest recognizable vertebrate remains, bone fragments of Upper Cambrian and Lower Ordovician heterostracan fishes, were deposited in a marine situation. 2. Since these earliest fossils are sporadic in occurrence, from atypical marine deposits and since they only represent the full grown adult stage, the possibility of a freshwater developmental stage or estuarine habitat cannot be excluded. 3. The hagfishes, supposedly the most primitive of living vertebrates, are exclusively marine and possess an osmoregulatory strategy (monovalent ion levels nearly identical with sea-water with little capability of regulation) that is consonant with a strictly marine evolutionary history. Possibly, but less parsimoniously, this strategy and habitat could be secondarily derived. 4. The hagfish has a glomerular kidney, renal sodium reabsorption and branchial pumps for the uptake of sodium and chloride which are indicative, but not unequivocally diagnostic, of a freshwater ancestry. 5. A scenario in which the earliest vertebrate was anadromous, breeding in fresh water and migrating to the sea, is consistent with the paleontological data and with the physiology and life history of living 'primitive' fishes. It also leads to more coherent explanations for the origin of bone and for the evolution of vertebrate special senses than do alternative marine scenarios. PMID- 2887337 TI - Comparison of recovery from hemorrhage in birds and mammals. PMID- 2887339 TI - The efficiency of growth during body weight recovery in young adult female rats. AB - 1. Six young adult female rats were subjected to 40% body weight loss in 84 days by food restriction followed by recovery of body weight in 36.2 +/- 4.28 days by ad libitum food intake. The regimen was then repeated, with 40% body weight loss in 105 days followed by recovery of body weight in 22.8 +/- 2.00 days. 2. Food intakes were measured continuously. 3. These rats used digestible energy more efficiently during the second recovery (49.1 +/- 3.11 v. 77.3 +/- 7.91 kJ digestible energy intake per g body wt gain). 4. Seven rats were subjected to one body weight loss and recovery. Five of them had an efficiency of 44.1 +/- 3.34 kJ/g live wt gain which was not significantly different from that of the first group during their second recovery; they may not have been capable of improvement after a second deprivation. 5. It is concluded that some rats can adapt after a period of severe body weight loss and recovery to utilize food more efficiently during body weight recovery after a second episode. PMID- 2887338 TI - Electrical and mechanical activity in heart tissue of flounder and rainbow trout during acidosis. AB - 1. Twitch force and voltage across the sarcolemma were measured in heart tissue of flounder and rainbow trout. 2. For the trout heart, hypercapnia was followed by a loss of force and an action potential prolongation. 3. This was also observed for the flounder heart, but only initially. 4. About 5 min after the onset of hypercapnia, an increase in force and a shortening of the action potential occurred in the flounder heart. 5. After about 30 min of hypercapnia a decrease in force and a prolongation of the action potential slowly appeared. 6. These results can be interpreted in terms of a species-dependent effect of acidosis on the cellular Ca2+ handling and the influence of intracellular Ca2+ on the action potential. PMID- 2887341 TI - The postnatal development of serum zinc, copper and ceruloplasmin in the horse. AB - 1. Serum samples were collected from ten foals at predetermined times during the first 12 months following birth and zinc and copper concentrations and ceruloplasmin activity were evaluated. 2. Serum zinc concentrations were found to be quite variable with respect to age (range = 67-95 micrograms/dl). 3. Serum copper concentrations increased in a linear fashion from day 0 to day 28 before levelling off at 190-247 micrograms/dl. 4. Ceruloplasmin activity was found to correlate with the concentration of serum copper (r = 0.92) and reached a plateau at an activity of 30-38 IU by day 28. PMID- 2887340 TI - The effect of artificial photoperiodicity and antiandrogen treatment on the antler growth and plasma levels of LH, FSH, testosterone, prolactin and alkaline phosphatase in the male white-tailed deer. AB - 1. Artificial extension of day-length in adult male white-tailed deer during the autumn induced: (a) premature casting of antlers, early onset of the new antler growth and out of season mineralization, (b) early elevation of plasma levels of prolactin, LH, FSH, testosterone and alkaline phosphatase and (c) out of season hair molt. 2. Intramuscular administration of the antiandrogen cyproterone acetate immediately after velvet shedding induced: (a) dramatic reduction of testosterone levels in plasma, (b) premature casting in bucks with fully mineralized antlers and (c) renewal of bone rebuilding activity in incompletely mineralized antlers which resulted in blockage of casting. PMID- 2887342 TI - Measurement of 14CO2 evolution during tissue oxidation in vitro; an alternative to the Kontes well. AB - 1. An alternative method to the use of the disposable Kontes well for trapping 14CO2 produced in the course of biological oxidations is described. 2. A polyethylene miniature scintillation vial was used to contain the hyamine hydroxide-impregnated filter paper wick. 3. The two methods are compared in their abilities to trap 14CO2 produced directly by acidification of sodium [14C]bicarbonate and during beta-oxidation of 1[14C] palmitic acid. 4. The miniature vial and Kontes well methods showed similar efficiencies in the trapping of 14CO2 (97% and 95%, respectively, on average) the radioactivity of which was determined in the miniature vial using 5 ml only of scintillation fluid compared with a minimum of 10 ml required by the standard scintillation vial used to accommodate the Kontes well. 5. The technical advantages of the suggested miniature vial system, during both incubation and counting stages, are discussed. PMID- 2887343 TI - Carrier-mediated transport of urate by chicken (Gallus domesticus) renal brush border membrane vesicles. AB - 1. Urate is transported by an anion exchange system in chicken renal brush-border membrane vesicles. An outward chloride gradient stimulates an overshoot in urate uptake. 2. The anion exchanger is similar to those described for the kidneys of rats and dogs except that the chicken exchanger has a higher specificity for urate. 3. p-Aminohippurate has only a weak affinity, if any, for the urate exchanger. 4. There were no apparent qualitative differences in urate transport between brush-border membrane vesicles from genetically normouricemic and hyperuricemic chickens. PMID- 2887344 TI - Fluid compartmentation in skeletal muscle and carcass of Mus musculus acclimated to water scarcity. AB - 1. Total water (TW), and extracellular water (ECW) (as sodium and chloride space) were determined in skeletal muscle and carcass of Mus musculus acclimated to long term water shortage. 2. The presence of fat in control mice and those in early stages of acclimation resulted in an apparent increase in TW and ECW as acclimation proceeded. 3. In contrast, fluid volumes per fat-free weight were either unchanged from controls or reduced. 4. Sodium space exceeded chloride space. 5. Muscle and carcass had essentially the same pattern of fluid shifts. 6. We conclude that ECW maintenance is a preeminent component of the acclimation process in this species. PMID- 2887345 TI - The effects of starvation and refeeding on egg laying and the synthetic activity of the albumen gland in Bulinus truncatus, a snail vector of urinary schistosomiasis. AB - 1. The effects of starvation (for 1, 2, 3, 6, 9 and 12 days, respectively) and refeeding (12 days starvation and 1, 2 and 3 days refeeding, respectively) on egg laying and albumen gland activity in the freshwater snail, Bulinus truncatus were studied. 2. The egg laying of starving snails rapidly decreased and ceased by day 6 of starvation. Egg laying was restored 24 hr after refeeding. The recorded decrease in albumen gland wet weight was proportional to the starvation periods. The DNA contents of the glands of the different experimental groups was not statistically different from the controls. 3. Albumen gland synthetic activity expressed as 14C-glucose incorporation into galactogen/microgram DNA and 3H-amino acids into total protein was determined. The glands showed an abrupt decrease in synthetic activity after 1 day of starvation and gradually decreased further until days 9-12. The decrease in activity of the glands was more rapid than that of egg laying. Upon refeeding, the activity of the glands recovered rapidly, simultaneous with the increase in wet weight and egg laying. 4. In conclusion, there is a correlation between egg laying and the in vitro activity of albumen glands. The results show a short-term effect of starvation on the fecundity of the snails. Such studies could be useful in field studies as well as snail control by applying molluscicides under optimal conditions. PMID- 2887346 TI - The effects of starvation and sexual maturation on Na+ transbranchial fluxes following direct transfer from fresh water to sea-water in rainbow trout (Salmo gairdneri). AB - 1. The perfused isolated head technique has been used to measure sodium arterial fluxes following direct transfer from fresh water to sea-water. 2. A starvation related decrease in net sodium flux is reported. 3. Sexual maturation slackens the decrement of this net flux. 4. In starved fish, the cytological modifications of chloride cells following such a transfer are delayed. 5. This effect of starvation is discussed in terms of lamella sodium imperviousness. PMID- 2887347 TI - Unilateral orchidectomy of ram lambs: acute, chronic and hCG-stimulated androgen levels. AB - 1. The objectives of this study were to determine whether compensation of androgen secretion occurred acutely, chronically or after hCG-stimulation in unilaterally orchidectomized (ULO) rams. 2. Testosterone (T) concentrations were not significantly different (P greater than 0.10) between ULO and sham-operated ram lambs during the period immediately following ULO. 3. Chronically, testosterone concentrations were not significantly different (P greater than 0.10) between ULO and sham-operated ram lambs. 4. After hCG injection, the testosterone response of chronic ULO ram lambs was approx. half the response of the sham-operated ram lambs. 5. These data indicate that a rapid and sustained compensatory response of basal secretion of testosterone but not hCG-inducible testosterone secretion occurred in the ULO'd ram lambs. PMID- 2887348 TI - Significance of sleeping plate as a thermal protection for farmed raccoon dogs (Nyctereutes procyonoides). AB - 1. Both living and model animals were used to evaluate the significance of a sleeping plate as a thermal protection for the farmed raccoon dog (Nyctereutes procyonoides, Gray, 1834), its use by the animals and its cleanliness while used. 2. A dry sleeping plate effectively prevented heat loss from the model animal while a wet plate was less effective. The degree of heat transfer was highest when the plate was ice-covered. Heat loss in windy conditions was significantly higher than in calm conditions. 3. The use of a sleeping plate did not depend on ambient air temperature; in spite of the cold weather (about -25 degrees C) only one in four animals preferred to lie on plate. Animals which did not prefer to use sleeping plates most eagerly messed them up. PMID- 2887349 TI - Effect of indomethacin on plasma levels of vitamin D metabolites, oestradiol and progesterone in rabbits during early pregnancy. AB - 1. Inhibition of prostaglandin (PG) synthesis by indomethacin (Id) during early pregnancy in rabbits apparently disrupts the process of sex steroid production by the ovaries. 2. The role of PGs as mediators in steroidogenesis was tested by investigating the effect of Id alone or in combination with progesterone, with oestradiol and progesterone, or with a mixture of PGs, on plasma levels of 25 hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) in rabbits at an early stage of pregnancy. 3. Id alone significantly reduced plasma levels of both 25(OH) D and 1,25(OH)2D. Treatment with Id in combination with either oestradiol and progesterone, or with a mixture of PGs, resulted in the restoration of plasma levels of both vitamin D metabolites as well as the restoration of plasma levels of progesterone, to their control values. PMID- 2887350 TI - Characterization of angiotensin I-converting enzyme activity in the freshwater turtle, Amyda japonica. AB - 1. Angiotensin I-Converting Enzyme (ACE) activity has been characterized in the freshwater turtle, Amyda japonica. 2. Peak activity of ACE in plasma from the freshwater turtle was shown at pH 9.0, which was more alkaline compared to that of mammals. 3. Chloride requirements for the optimal ACE activity were different from species. 4. ACE inhibitors, EDTA, teprotide (SQ 20,881), Captopril (SQ 14,225) showed dose-dependent inhibitions of ACE activity in plasma from the freshwater turtle as well as mammals. 5. ACE activity was found in several different tissues with a different activity showing the highest activity in kidney homogenate from the freshwater turtle, Amyda japonica. PMID- 2887351 TI - Electrophysiological characteristics of cardiac pacemaker cells of the frog Caudiverbera caudiverbera. AB - 1. The cardiac pacemaker cells of the frog Caudiverbera caudiverbera are centrally located in the sinus venosus. These cells are rounded, smaller than contractile fibres and have large nuclei. 2. Intracellular recording confirmed the existence of primary and transitional pacemaker cells. 3. Action potentials from primary cells were resistant to blockade by tetrodotoxin (TTX), but were abolished by verapamil suggesting that their bioelectric activity is dependent on a slow inward current. 4. Transitional cells appeared to have two different inward currents contributing to the upstroke: a fast TTX-sensitive and a slow verapamil-sensitive current. PMID- 2887352 TI - Intestinal release of mucin in response to HCl and taurocholate: effect of indomethacin. AB - 1. Alkaline secretion and mucin output were analyzed along the gastrointestinal tract of a dog in response to luminal application of HCl and taurocholate with and without pretreatment with indomethacin. 2. Mucins derived from the different areas displayed similar contents of protein and carbohydrate but differed with respect to associated and covalently bound lipids. 3. Application of HCl or taurocholate in all the regions caused an increase in the output of mucins and HCO3-. However, mucins elaborated in response to HCl exhibited higher total lipid content and were richer in phospholipids. 4. Pretreatment with indomethacin prior to HCl application led to a reduction in HCO3- and caused a decrease in mucin phospholipid content, but had no effect on HCO3- secretion and the lipid content of mucins elaborated in response to taurocholate. 5. The results indicate that mucins elaborated along the gastrointestinal tract differ with respect to lipids, and that their output in response to HCl is mediated by prostaglandins. PMID- 2887353 TI - Effect of thyroidal state on the gastrointestinal transit and emptying of young broilers. AB - 1. In newly hatched broilers, propylthiouracil and thyroid powder added to the diet produced hypothyroidism and hyperthyroidism, respectively. After 4-5 days of treatment body and thyroid weight changed, but no differences in body temperature were found. 2. The hyperthyroidal animals had high mortality rate and the hypothyroidal ones showed significantly lower glycemia values. 3. The gastrointestinal transit and emptying of 8 and 15 days old hypo-, hyper- and euthyroidal broiler chicks were measured using 14C-PEG-4000 as a marker. 4. Hypothyroidism prolonged GI transit and emptying, whereas hyperthyroidism modified these parameters in a way dependent of the elapsed time after the test meal: at 0.5 and 1 hr transit and emptying were quick, but at 2 and 4 hr the transit was slow. 5. Hyperthyroidism also delayed the transit of large bowel intraluminal contents in 15-day-old chickens. 6. These results are very similar to those of starvation, suggesting an important interaction between diencephalon, thyroid gland and GI motility in young chickens. PMID- 2887355 TI - Fluid volumes in rainbow trout, Salmo gairdneri: application of compartmental analysis. AB - 1. The measurement of fluid volumes by the indicator dilution technique and compartmental analysis was re-evaluated in free-swimming, undisturbed rainbow trout. 2. Plasma (33.5 ml/kg body wt) and blood (41.3 ml/kg body wt) volumes estimated by compartmental analysis from blood samples taken early (less than 5 min) after dye injection were 40% lower than volumes calculated by sampling late (greater than or equal to 80 min). 3. The rate of exchange of dye between plasma and interstitial fluid was high (48%/hr) compared to mammals (5%/hr) which supports the hypothesis that teleost capillaries have high protein permeability. 4. Total extracellular volume estimated using a single pool model (210.5 ml/kg body wt) of inulin kinetics was 20% higher than that calculated by a three pool model (172.8 ml/kg body wt). PMID- 2887354 TI - Influence of dietary fat on some metabolic responses of cattle to hyperthermia induced by heat exposure. AB - 1. Two breeds of cattle which differ in their plasma concentrations of lipid components (PCLC) and ability to tolerate heat were used to study metabolic responses to hyperthermia. Two maintenance diets, LF (2.5% Fat) and HF (9.2% Fat), which were isonitrogenous and isocaloric were used. 2. The PCLC, the net esterification of cholesterol by the lecithin: cholesterol acyl transferase system and faecal fat excretion were increased by the HF diet which reduced urinary N loss. 3. Hyperthermia disturbed lipid metabolism in all animals and reductions in the concentrations of plasma cholesterol and phospholipid paralleled the increases in the quantities of fat excreted in the faeces. 4. Within breeds the animals on the HF diet maintained a higher PCLC, lower body temperature and conserved more body nitrogen during hyperthermia than animals on the LF diet. 5. The results point to a role for dietary lipid in ameliorating the metabolic disturbances in animals during chronic hyperthermia. PMID- 2887356 TI - L-antigen and active potassium transport in HK and LK red cells of Barbary sheep (Ammotragus lervia). AB - 1. The potassium concentration in red cells of 21 Barbary sheep showed a bimodal distribution, with five animals of LK type (K+ conc. 30-45 mM) and 16 of HK type (K+ conc. 80-95 mM). 2. Evidence is presented that both Lp and Ll antigens are present on LK Barbary sheep red cells. 3. Active K+ transport in LK Barbary sheep red cells was stimulated 3-5 fold by sheep and goat anti-L. 4. Active K+ transport in HK Barbary sheep red cells was higher than in LK red cells. Five out of six HK animals tested showed no stimulation of active K+ transport with anti L. One HK animal (2BA2) showed some stimulation of active K+ transport, and also absorbed some anti-L from antisera, suggesting that Lp antigen is present on these red cells. 5. Ouabain-sensitive ATPase in membranes from HK and LK Barbary sheep red cells showed kinetics characteristic of HK and LK membranes of domestic goats and sheep; the ATPase of LK Barbary sheep membranes sensitized with anti-L was stimulated 2-fold due to an alteration in the internal sodium and potassium affinities in favour of sodium. PMID- 2887357 TI - Absorption and fate of labelled canthaxanthin 15, 15'-3H2 in rainbow trout (Salmo gairdneri Rich.). AB - 1. Using one force fed meal, absorption of labelled canthaxanthin 15,15'-3H2 was studied by collecting blood via caudal punction at regular intervals and measuring radioactivity in various tissues and organs of rainbow trout. 2. Canthaxanthin absorption showed a large variability between individuals irrespective of their sex. A rapid increase in the radioactivity linked to canthaxanthin 15,15'-3H2 is observed in the blood followed by a slow decrease. 3. Twenty-four and 72 hours after ingestion of labelled canthaxanthin by rainbow trout, the radioactivity was widely distributed. From the total radioactivity given, most was found 24 hours after the meal in the pyloric caeca, ovary and skin. Seventy-two hours after diet, the radioactivity increased in the muscle, liver and kidney. On the other hand, the percentage of radioactivity of intestine and caeca declined. 4. Data from absorption curve indicates that 0.86% of radioactivity ingested is present in the blood, suggesting that canthaxanthin is not readily transferred from the digestive tract. 5. The metabolic clearance of canthaxanthin (lambda = 0.0246/hr +/- 0.005) which would correspond to a half life of 28 hours gives a preliminary idea of the digestive and metabolic utilization of canthaxanthin by the rainbow trout. PMID- 2887358 TI - Post-tetanic potentiation of miniature end-plate potential frequency at neuromuscular junction of the rat soleus muscle. AB - 1. Changes in miniature end-plate potential (m.e.p.p.) frequency by repetitive nerve stimulation were examined in the rat soleus muscle. 2. The increase of m.e.p.p. frequency was induced by repetitive stimulation and persisted for several minutes after the tetanus. That is, post-tetanic potentiation (PTP) of neuromuscular transmission was first demonstrated here in the rat soleus muscle. 3. The time course of the decay of m.e.p.p. frequency after the tetanus showed a double exponential curve which consisted of a fast decaying component (augmentation) and a slow decaying component (potentiation). 4. The magnitude of PTP depended on the stimulation frequency and its duration. It increased with the increase of duration and was at its maximum at a frequency of 100 Hz. 5. No PTP was elicited by repetitive stimulation under conditions in which end-plate potential (e.p.p.) was completely suppressed, and, moreover, m.e.p.p. frequency tended to decrease after the tetanus. PMID- 2887359 TI - Transient sensitivity reduction and biphasic photoresponses observed when frog retinal rods are oxidized. AB - 1. Rod photoresponses and the effects of oxidation have been studied by recording either the transretinal voltage in aspartate-treated retinas or the outer segment current of single rods. 2. Oxidizing conditions transiently decreased, reducing conditions increased sensitivity. 3. Biphasic photoresponses were seen when the level of oxidation was rising and also in some other sensitivity-depressing conditions. 4. A model is proposed which explains the biphasic responses in terms of sensitivity differences between the tip and the base of the rod outer segment. PMID- 2887360 TI - Serum levels of bilirubin and biliverdin in the sea lamprey, Petromyzon marinus L., before and after their biliary atresia. AB - 1. The sera of ammocoetes, juvenile adults, and upstream migrants of the sea lamprey, Petromyzon marinus L., were analyzed for the presence of the bile pigments, biliverdin and bilirubin. 2. Bile pigment was not detected in the sera of ammocoetes. 3. After biliary atresia (degeneration of bile ducts at metamorphosis), bilirubin and biliverdin were detected in the sera of both juvenile adults and upstream migrants. 4. These data suggest that lampreys have some bile stasis following biliary atresia, but also that they likely have alternate pathway(s) for bile pigment elimination. PMID- 2887361 TI - Effect of photoperiod on the diurnal rhythm of plasma testosterone, dihydrotestosterone and androstenedione in mature male chickens. AB - 1. The effects of different photoperiods on the concentrations of plasma androgens, testes weight and on the diurnal rhythm of plasma testosterone (T), dihydrotestosterone (DHT) and androstenedione (A) in mature, single comb White Leghorn male chickens were studied. 2. Birds were exposed to either 14 hr of light (lights on at 0600-2000 hr) or to 24 hr of light per day. 3. Blood samples were collected from birds in both groups at 3-hr intervals and plasma levels of T, DHT and A were measured using radioimmunoassays. Following blood collection, birds were weighed, killed and testis weights were recorded. 4. Under 14 hr of light, there was a diurnal rhythm of T and DHT with hormone concentrations peaking at the end of the dark period. There was no obvious rhythm for A. Exposure to 24 hr of light abolished the diurnal rhythm found under 14 hr of light. 5. There was an increase not only in testis weights but also in body weight and hormone concentrations under 24 hr of light. 6. It was concluded that photoperiod plays an important role in controlling the concentration and rhythm of androgens in mature male chickens. PMID- 2887363 TI - Changes in post-tetanic potentiation of neuromuscular transmission in chronically stretched muscle. AB - 1. Changes in the parameters of the magnitude of PTP of m.e.p.p. frequency were examined in rat soleus muscles chronically stretched for a variety of durations (4-28 days) by leg-lengthening operations. 2. On day 4 after the operation, the magnitude of PTP in the stretched muscles obviously increased compared to the control muscles. This indicates that Ca2+-conductance in the nerve terminals increases in the stretched muscles at day 4. 3. On day 7 after the operation, there was no significant difference between the magnitudes of PTP in the control and stretched muscles. 4. After day 14 following the operation, the magnitude of PTP in the stretched muscles was smaller than that in the control muscles. This indicates that Ca2+-conductance in the nerve terminals decreases in the stretched muscles after day 14. PMID- 2887362 TI - Biomphalaria glabrata: respiration, calcium and end products of carbohydrate metabolism. AB - 1. Lactic acid and succinic acid (end products of anaerobiosis) also occur under aerobic conditions in the haemolymph and excretion products of Biomphalaria glabrata. This phenomenon has been investigated in more detail. 2. Experiments on oxygen uptake, and analyses of organic acid, amino acid and calcium were carried out under various aerating conditions, various temperatures and in various water qualities. 3. No differences were found in the concentrations of the organic acids and calcium in the haemolymph under different aerating conditions. 4. Neither snail-conditioned water, nor artificial crowding effects played a role in the initiation of anaerobic respiration. 5. A low exposure temperature (4 degrees C) initiated anaerobic respiration in spite of the aeration. PMID- 2887365 TI - Muscle capillarity in chicks following hypoxia. AB - 1. Muscle capillarity was examined in chicks exposed to normobaric hypoxia with and without increased workload. 2. Capillarity was higher in the lateral head of the gastrocnemius, but not in the other muscles examined. Increased workload did not contribute to the effects of hypoxia. 3. Thus, hypoxia served as a stimulus for the development of new capillaries in muscle containing twitch fibers, but not in muscle containing tonic fibers. PMID- 2887364 TI - Ecdysteroids during embryonation of eggs of Ascaris suum. AB - 1. The optimal temperature for in vitro development of fertilized eggs of Ascaris suum was 24 degrees C. 2. Samples (2 X 10(7) eggs) were obtained from in vitro embryonating cultures every 3 days for 4 weeks; lipids were extracted, partially purified, fractionated with HPLC and analyzed for ecdysteroids by radioimmunoassay. 3. Free ecdysone and 20-hydroxyecdysone (20-HE) were at low levels (less than 20 pg) in freshly excised eggs and rose to maximal values on day 6 of embryonation. 4. Conjugated ecdysone and conjugated 20-HE rose to maximal values on day 9. 5. Both free and conjugated ecdysteroids were undetectable from days 15 to 27 of cultivation. 6. These profiles indicate that ecdysteroids might have a selective role in nematode embryonation and/or tanning of the egg shell. PMID- 2887366 TI - Possible mechanism of unconjugated bilirubin toxicity on renal tissue. AB - 1. The effects of unconjugated bilirubin on rat renal tissue metabolism and organic anion transport were investigated using cortical slices. 2. Unconjugated bilirubin in the medium decreased slice-to-medium ratio of p-aminohippurate, altered intracellular Na+ and K+, and decreased ATP content without modifications of (Na+-K+) ATPase. 3. The effects were similar to those of ethacrynic acid and cyanide but less marked. 4. The presence of probenecid blocked the effect of pigment on intracellular electrolytes. 5. The results suggest that pigment is taken up by renal tissue using the organic anion transport system, and within the cell inhibits ATP production. PMID- 2887367 TI - Environmental effect on plasma thyroxine (T4), 3,5,3'-triido-L-thyronine (T3), prolactin and cyclic adenosine 3',5'-monophosphate (cAMP) content in the mudskippers Periophthalmus chrysospilos and Boleophthalmus boddaerti. AB - 1. In both Periophthalmus chrysospilos and Boleophthalmus boddaerti, T4 was involved in enabling the fish to cope with terrestrial stress and not in osmoregulation in waters of different salinities. In B. boddaerti, however, 3,5,3'-triiodo-L-thyronine (T3) played a more significant role in osmoregulation under the various aquatic conditions. 2. The control of osmoregulation mechanisms in P. chrysospilos kept in waters of different salinities was taken over by prolactin instead, whereas prolactin was only involved in osmoregulation in B. boddaerti under extreme osmotic stress (100% SW). Prolactin is also involved in the terrestrial adaptations of P. chrysospilos. 3. Plasma cAMP levels in P. chrysospilos increased with increasing salinity of the external environment (Tables 4 and 5) implicating its role in the stimulation of chloride secretion and in intracellular isosmotic regulation. 4. Significant increase in the plasma cAMP level of B. boddaerti submerged in 100% SW was also observed. However, the plasma cAMP levels of B. boddaerti fully submerged in 30% and 50% SW were not significantly different from the control as these conditions simulated those of their natural habitats. PMID- 2887368 TI - Fever in snails, reflection on a negative result. AB - 1. Groups of aquatic snails (Limnaea auricularia) were placed in a temperature gradient and their thermopreferendum measured. 2. Injected with various amounts of killed Escherichia coli, bacterial endotoxin, human interleukin, and prostaglandin E1, E2 and F2 alpha, they did not develop a fever. 3. High doses of prostaglandins were toxic. 4. These results suggest that fever appeared in the course of evolution after the emergence of molluscs and before that of arthropods. PMID- 2887369 TI - Effect of feeding pattern on the sensitivity of hepatic carnitine palmitoyl transferase to inhibition by malonyl-CoA in the rat. AB - 1. The feeding pattern influences the inhibitory effects of malonyl-CoA on carnitine palmitoyltransferase-I. 2. The sensitivity of liver carnitine palmitoyltransferase-I to malonyl-CoA is increased in rats meal-fed when compared to rats fed ad libitum. 3. Moreover, liver carnitine palmitoyltransferase-I of meal-fed rats remains more sensitive to inhibition by malonyl-CoA during a 24 hour fast than liver carnitine palmitoyltransferase-I of rats previously fed ad libitum. PMID- 2887370 TI - Calcitonin induces hypercalcemia in grey mullet and immature freshwater and sea water adapted rainbow trout. AB - 1. Changes in plasma calcium levels, in response to salmon calcitonin injections, were studied in freshwater and sea-water adapted trout (Salmo gairdnerii) and in grey mullet (Chelon labrosus). 2. Low doses (0.1 ng sCT/100 g body weight) elicited hypercalcemia in the two species studied. 3. High doses (0.5 microgram) provoked hypocalcemia only in freshwater and sea-water adapted trout. 4. An hypercalcemic response appears as the primordial effects of CT injections, higher doses of CT leading to hypocalcemic effects. PMID- 2887372 TI - Reduced synthetic activity as a contributing factor to weight-loss in the circannual cycle of Richardson's ground squirrels. AB - 1. Glycogen concentrations in Richardson's ground squirrels of the weight-loss phase were 1/4-1/2 those in animals of the weight-gain phase. White adipose lipid content was similar in animals in the two phases when total body weight was similar. 2. Specific activity of 14C in muscle glycogen of fed, starved and refed ground squirrels in the weight-loss phase was similar to that in starved weight gain phase animals. Activity in adipose lipids of fed, starved, and refed ground squirrels in the weight-gain phase was 5-8 times greater than that in the same nutritional states in weight-loss phase animals. 3. In addition to a voluntary reduction in food intake, a depressed synthetic activity in lipids and glycogen may account in part for the rapid decrease in body weight during the weight-loss phase of the circannual cycle. PMID- 2887371 TI - Effect of diabetes on natriuresis in the presence of ouabain and ethacrynic acid in perfused rat kidney. AB - 1. The effect of diabetes on renal sodium retention was investigated. 2. The technique involved retrograde perfusion from the renal veins via the kidneys, and then through the renal arteries and dorsal aorta. 3. Sodium retention by diabetic rat kidney was 58% lower than that in the normal rats. 4. Ouabain (15 mM) in perfusate increased sodium retention by 30% in normal rat kidney as compared to a 54% increase in diabetic rat kidney. 5. Ethacrynic acid (1 mM) in perfusate resulted in a 42% reduction in sodium retention in the normal rat kidney as compared to a 43% decrease in the diabetic rat kidney. 6. Control of hyperglycemia in diabetic rats with insulin therapy resulted in sodium retention that is not significantly different from that of normal rats. 7. The results suggest that diabetes has no effect on the peritubular ouabain-sensitive Na--K ATPase pump, or the luminal ethacrynic acid-sensitive Na-K counter transport pump. Furthermore, the data suggest a reversible effect of diabetes on sodium retention during insulin therapy. PMID- 2887373 TI - Some regulatory aspects of thermogenesis in cold-exposed piglets. AB - 1. Thermoregulatory mechanisms were studied in weaned piglets fed ad libitum for 3 weeks at 12 or 23 degrees C. 2. Cold-adapted pigs maintained a growth rate and a carcass composition similar to the control ones, while increasing food intake by 20% (P less than 0.05). 3. Lipoprotein lipase activity was increased (P less than 0.05) by cold exposure in white adipose tissue (WAT) and heart. A large enhancement of lipogenesis was observed in WAT and to a lesser extent in the liver while WAT composition did not change significantly in the cold. 4. Cytochrome oxydase activity was increased in liver (30%), perirenal fat (40%) and interscapular muscle (75%) of cold-exposed pigs. 5. Plasma levels of thyroid hormones (TSH, T3, T4) were increased in the cold. 6. Mechanisms and locations of heat production are discussed. PMID- 2887374 TI - Contraction of spleen in exercised cyprinid. AB - The spleens of five cyprinid fish contracted fully within 3-30 min from start of severe exercise, and then decreased 63-85% in weight and 72-93% in hemoglobin content. PMID- 2887375 TI - Anaerobic metabolism and activity of European lacertid lizards. AB - 1. Lactate production and physical performance during intense activity were measured in Lacerta vivipara, Podarcis muralis and Podarcis hispanica, temperate lizards from progressively lower latitudes. 2. Rates of lactate production during the initial 30 sec of bursts of activity (means = 1.75 mg g-1) and their Q10S (means = 1.36) are similar to previously obtained values for lizards. 3. Maximal anaerobic scope at activity body temperatures is lowest in Lacerta vivipara, which correlates with a tendency to less strenuous behaviour than that of the Podarcis species and may reflect the need for energy economy. 4. Q10S of maximal performance are lower in Lacerta vivipara and Podarcis muralis than Podarcis hispanica, a difference having no demonstrated metabolic basis but which is thermally adaptive for these cooler climate species. PMID- 2887376 TI - Hibernation in garter snakes (Thamnophis sirtalis parietalis): seasonal cycles of cold tolerance. AB - 1. The red-sided garter snake hibernates for about six months each year in Manitoba, Canada, where winter temperatures are often as low as -40 degrees C. Mammalian hibernators typically undergo profound changes in preparation for hibernation, but little is known about corresponding changes in reptiles. 2. We tested the importance of seasonal changes in the ability of red-sided garter snakes to hibernate successfully by exposing them to winter conditions at different times of year. 3. Animals that began hibernation in the fall were more likely to survive hibernation than animals that began hibernation in either early or late summer, despite the fact that the animals were kept on seasonally constant conditions prior to hibernation. 4. We suggest that these changes are derived from endogenous components of the yearly hibernation cycle of red-sided garter snakes but that only part of the cycle proceeds endogenously, i.e. it is not a completely endogenous circannual cycle. PMID- 2887377 TI - Supplementation of Ham's F10 culture medium with three different sera in the culturing of baboon oocytes. AB - 1. Ten female baboons (Papio ursinus) were stimulated for a total of 20 cycles with 3 ovulation induction agents. 2. Oocytes obtained were randomly allocated to Ham's F10 culture medium supplemented with human fetal cord serum, primate serum or commercial fetal bovine serum respectively. 3. Fertilization occurred (38.1 45.5%) in all 3 supplements, but cleavage and embryo development was more successful in culture medium supplemented with fetal bovine serum. 4. Eight embryos were cultured and 6 (75%) of these were cultured in fetal bovine serum supplemented medium. PMID- 2887378 TI - Pituitary-induced lactation in mammary gland explants from the pregnant tammar (Macropus eugenii): a negative role for cyclic AMP. AB - 1. alpha-Lactalbumin and casein have been isolated from tammar milk. 2. alpha Lactalbumin was induced in mammary explants by culture with anterior pituitary. 3. Casein was induced maximally in the presence of a physiological concentration of prolactin alone. 4. Progesterone did not inhibit the prolactin-induced synthesis of casein, alpha-lactalbumin, galactosyltransferase or fatty acids. 5. Both dibutyryl cAMP and a combination of cholera toxin and IBMX did significantly inhibit the induction of casein and alpha-lactalbumin. 6. Progesterone withdrawal is not a component of the lactogenic trigger in this marsupial but cAMP may be a common intracellular signal for negative control of lactogenesis in both marsupials and eutherians. PMID- 2887379 TI - Na+ + K+-ATPase activity and transport processes in toad corneal epithelium. AB - 1. Ascorbic acid, diamide and N-ethylmaleimide inhibit Na+ + K+-ATPase activity in toad corneal epithelium. 2. Ascorbic acid, diamide and N-ethylmaleimide increase alpha-aminoisobutyric acid accumulation in this tissue. 3. The effects of these compounds on corneal amino acid and ion transport are not mediated through alterations in Na+ + K+-ATPase activity. PMID- 2887380 TI - Hematocrit and blood chemistry values in captive raptors (Gyps fulvus, Buteo buteo, Milvus migrans, Aquila heliaca). AB - 1. Eight hematological values were determined in blood samples from 88 raptors representing 10 species. 2. Means, standard errors, ranges and coefficients of variations were obtained for each parameter and species investigated. 3. The griffon vulture (Gyps fulvus) showed mean concentrations of glucose lower than those of most of the other species. 4. Concentrations of urea in the buzzard (Buteo buteo) were higher than those of the other raptors studied, and the black kite (Milvus migrans) had cholesterol values greater than the other species. 5. Blood values of individual birds of prey in good and bad states of nutrition were compared, showing significant changes in cholesterol, hematocrit, urea and total protein values. PMID- 2887381 TI - Perfluorocarbons as oxygen-transport fluids. AB - 1. An overview of the proposed biological applications of perfluorocarbons and their emulsions as oxygen-transport fluids is presented. 2. Aspects of the properties, preparation, composition and physiological assessment of perfluorocarbon emulsions are discussed. 3. The experimental basis for some of the potential therapeutic uses of PFCs in liquid ventilation, treatment of decompression sickness, organ perfusion, oxygenation of ischaemic and malignant tissues, and as contrast media for NMR imaging is described. 4. The extent to which emulsified perfluorocarbons may have value as substitutes for red blood cells is discussed in detail. Data from both animal and human studies with such emulsions is reviewed. Brief consideration is also given to the possible use of native and modified haemoglobin in blood replacement together with recent work on the preparation of so-called "synthetic red cells". PMID- 2887383 TI - Capillary growth and diffusion distances in muscle. AB - 1. Tissue capillarity in muscle was modelled as square-ordered arrays with capillary-to-fiber ratios (C/F) from 0.5 to 'infinity'. 2. C/F up to two had marked effects on diffusion distances, but C/F above had only slight effects on average distances and almost no effect on maximal distances. 3. Capillary growth during normal maturation results in C/F around two. Thus, capillary growth in adult muscle may not be an adaptive mechanism for reducing diffusion distances. PMID- 2887382 TI - Acid phosphatase activity in pre- and post-spawning hake (Merluccius hubbsi). AB - 1. The specific activity of muscle acid phosphatase (E.C. 3.1.3.1.) in pre- and post-spawning hake was investigated. 2. Specific activity values, 0.54 in pre spawning hakes and 1.64 in post-spawning fish, have been obtained. 3. Using a histochemical test, acid phosphatase has been localized mainly in the connective tissue. The strongest reaction has been observed in post-spawning hake. 4. The increase of the lysosomal activity in the connective tissue may be related to the changes found in the muscle texture associated with spawning. PMID- 2887384 TI - Redifferentiation and subsequent dedifferentiation of the livers of roosters resulting from acute estrogen challenges. AB - 1. Histologic and metabolic changes take place in livers of rooster receiving challenges consisting of acute doses of estrone. 2. During initial Growth and Redifferentiation livers rapidly increase in size by division of hepatocytes within most lobules, changing from cordlike to acinar configurations. 3. No new lobules appear and degeneration of some cells within lobules takes place even as cell divisions predominate. 4. Cells within lobules assume secretory features. 5. Vitellogenins, very low density lipoproteins, calcium and alkaline phosphatase increase greatly in plasma. 6. Within 35-40 days of cessation of estrogen, livers have returned to near normal sizes and plasmas exhibit normal parameters. PMID- 2887385 TI - Changes in cell membrane fluidity affect the sodium transport across frog skin and its sensitivity to amiloride. AB - 1. 1-5 mM n-hexanol added to the outer (mucosal) medium of isolated skin of the frog Rana temporaria increases the short circuit current (Isc) across it. 2. This effect shows a saturable dependency on the outer sodium concentration, also when NaCl is replaced by Na2SO4. 3. n-Hexanol at a concentration of 1 mM, and cold acclimation of the frogs, which increases the fluidity of epidermal cell membranes, do not affect the sensitivity of Isc to the inhibiting effect of amiloride. 4. n-Hexanol at a concentration (5 mM) which causes a fluidization of cell membrane preparations from isolated frog epidermis also increases the sensitivity of Isc to amiloride. 5. The effects of low concentrations of n hexanol and of cold acclimation probably depend on an increase of the permeability of apical membranes of epidermal cells to sodium caused by membrane fluidization. At higher concentrations of n-hexanol, a further disordering of the membrane structure occurs with a better access of amiloride to its action sites. PMID- 2887386 TI - Mechanisms of transport of Na+ and Cl- in the lizard colon. AB - 1. Ionic fluxes of sodium and chloride across lizard colon mucosa were measured and compared with the electrical characteristics of the tissue under voltage clamped conditions. 2. In a Ringer-bicarbonate solution there was both a net sodium flux (JNanet) and a net chloride flux (JClnet) from mucosa to serosa. The net flux residual (JR) was near zero, indicating that net sodium and chloride transport is the result of an electrically neutral transport mechanism. 3. In the presence of sodium, the net chloride flux was abolished and the short-circuit current (Isc) and the electrical potential difference (PD) were unchanged. In the absence of chloride the net sodium flux was abolished and the short-circuit current and electrical potential difference were not modified. 4. From an analysis of the effects of the inhibitors, furosemide, amiloride and disulfonic stilbene (DIDS), a plausible model was developed to explain the characteristics of sodium and chloride absorption. PMID- 2887387 TI - Primate in vitro fertilization research: preliminary results on the folliculogenic effects of three different ovulatory induction agents on the chacma baboon, Papio ursinus. AB - 1. A study was conducted on the chacma baboon, Papio ursinus with three ovulation induction agents in an effort to define a preferential stimulatory protocol with regards to the number and quality of oocytes obtained. 2. Three folliculogenic agents applied in four stimulatory protocol regimens comprised clomiphene citrate in a high (100 mg/day) and low (50 mg/day) dosage, a combination of clomiphene citrate and pregnant mare serum, and human menopausal gonadotropin. 3. A total of 159 oocytes were aspirated by laparotomy from 10 baboon females in 20 induced cycles with an average of 8.0 +/- 5.4 oocytes per aspiration. 4. The highest mean number of oocytes (11.3 +/- 6.7) were obtained with the clomiphene/pregnant mare serum gonadotropin combination. 5. The best fertilization rate was obtained with clomiphene 50 mg. 6. The highest incidence of oocytic cleavage and embryo transfer were achieved with human menopausal gonadotropin (14.8%). PMID- 2887388 TI - Time courses of thermal acclimation for critical thermal minima in the salamanders Desmognathus quadramaculatus, Desmognathus monticola, Desmognathus ochrophaeus, and Plethodon jordani. AB - 1. We examined the time courses of thermal acclimation for critical thermal minima (CTMin) in the salamanders Desmognathus quadramaculatus, D. monticola, D. ochrophaeus, and Plethodon jordani. 2. D. quadramaculatus showed no annual differences in their time courses, but we noted seasonal differences in the CTMin with these salamanders having lower CTMin in the spring. 3. Gain in CTMin (25 degrees C to 5 degrees C transfer) was faster than its corresponding loss (5 degrees C to 25 degrees C transfer) in D. quadramaculatus. 4. Comparison of all three Desmognathus species revealed no differences in the CTMin for the 5 degrees C to 25 degrees C time courses, but P. jordani had lower CTMin than corresponding D. quadramaculatus. 5. Our results indicate that the pattern of CTMin acclimation correlates with the constraints acting on salamanders in their natural environment. PMID- 2887389 TI - Pyrogens fail to produce fever in the snakes Psammophis phillipsii and Lamprophis fuliginosus. AB - 1. Preferred body temperature of five diurnal, Psammophis philipsii and three nocturnal, Lamprophis fuliginosus, snakes was measured in a thermal gradient chamber by indwelling colonic thermocouples, before and after injection of a variety of pyrogens. 2. The snakes achieved their preferred body temperature by moving up and down in the gradient chamber; it was about 33 degrees C for P. phillipsii and 25 degrees C for L. fuliginosus. 3. The snakes did not develop fever in response to any of the pyrogens, whether gram-negative or gram-positive in origin, either on the day of injection or on the subsequent day. 4. We believe that fever is rare amongst reptiles. PMID- 2887390 TI - Work performance, thermoregulation and muscle metabolism in thyroidectomized goats (Capra hircus). AB - 1. Thyroid hormone deficiency resulted in a markedly diminished work efficiency of goats exercising on a treadmill at an ambient temperature of 30 degrees C. 2. The close relationship between the exercise-induced increase in core temperature and the magnitude of evaporative heat loss, characteristic for intact animals, was nearly completely abolished after thyroidectomy. 3. Muscle glycogen utilization and lactic acid accumulation during exercise were enhanced in thyroidectomized animals in spite of the lower work rate and shorter duration of exercise in comparison with euthyroid goats. PMID- 2887391 TI - Leukocyte numbers in hemorrhaged Japanese quail after microwave irradiation in ovo. AB - 1. Coturnix coturnix japonica eggs were exposed to 2.45-GHz continuous wave microwave radiation at an incident power density of 5 mW/cm2 (and a specific rate of 4 mW/g) during the first 12 days of embryogeny. After hatching, hematological changes in response to an acute hemorrhage were measured in exposed and nonexposed (control) juveniles of both sexes. 2. Exposure did not affect erythroid cell numbers either before or after hemorrhage. 3. Exposure affected the recovery of lymphocyte and heterophil numbers after hemorrhage, but the effect was sex-limited. 4. These data indicate that microwave irradiation during embryogeny in ovo affects the ability of Japanese quail to recover from an acute and voluminous hemorrhage and that these radiation effects are sex-limited and consistent with a previous report. PMID- 2887392 TI - Hematological response of hemorrhaged Japanese quail after blood volume replacement with saline. AB - 1. Hematological responses to hemorrhage by phlebotomy with and without replacement of blood volume with saline were measured in juvenile and adult male Coturnix coturnix japonica. 2. Recovery of total peripheral erythrocyte numbers and total peripheral leukocyte numbers occurred within 72 hr postphlebotomy in both treatment groups. 3. Saline replacement of blood volume following hemorrhage increased the total numbers and differential percentages of circulating reticulocytes at 72 hr postphlebotomy above the reticulocyte values of phlebotomized quail receiving no saline in both adult and juvenile Japanese quail. PMID- 2887393 TI - Iron metabolism in iron-deficient male quail. AB - 1. Male quails submitted 20 and 120 days to a low iron diet (7 ppm) were compared to female laying quails, exposed for 30 days to the same low iron regime, in order to compare the response of the iron metabolic control under a single (erythropoiesis) or a doubled (erythropoiesis and egg formation) iron demand. 2. Iron deposit in storage organs, the classical hematology and the intestinal iron absorption were analyzed in these animals. 3. In males, after 120 days, the iron deposits were reduced 50 and 75%, but hematological values (hematocrit and hemoglobin concentration) were normal, although in laying quails, after 30 days, an anemic condition was evident in both blood parameters and iron deposits, provoking an iron deficient erythropoiesis. 4. The enhancement of the intestinal iron uptake, confirms the anemic character of these birds. PMID- 2887394 TI - Role of exchange transport in the absorption of L-tryptophan in the small intestine of chicks. AB - 1. In in vitro experiments with accumulating mucosal preparations (AMP) and everted intestinal sacs, as well as in in vivo experiments with isolated loops of the small intestine the stimulating effect of a number of amino acids on L tryptophan uptake was investigated. 2. Under "switched off" active transport (anoxia, 2,4-DNF treatment, sodium ion replacement by lithium ions in the mucosal solution) an expressed stimulation of L-tryptophan transport was observed within the mucosa and across the wall of the small intestine in the presence of L proline, glycine, L-alpha-alanine, L-histidine and L-lysine. 3. Preincubation of AMP in the solutions of glycine, L-alpha-alanine and L-lysine was characterized by a stimulation of L-tryptophan transport, and the increase of its concentration in tissue was accompanied by the exit of an equivalent amount of glycine from it. 4. These observations show the participation of exchange transport in the uptake of L-tryptophan in the small intestine of chicks. 5. The mechanism of exchange transport in chicks starts to function on the 25th day after hatching and its intensity depends on the character of amino acid-modifier participating in the process. 6. Maximum activity of the exchange transport of L-tryptophan is demonstrated in the middle ileum. 7. L-alpha-Alanine stimulates the absorption of L-tryptophan from the isolated intestinal loop proving the existence of an exchange transport mechanism in a living organism. 8. An increased intensity of exchange transport is observed when feeding chicks with diets deficient and enriched in tryptophan. PMID- 2887395 TI - The effects of ligation of the oesophagus on body and brain temperature in pigeons. AB - 1. We measured brain and colonic temperatures in adult pigeons (Columba livia) with or without oesophageal ligation, and with or without simultaneous eye covering at ambient temperatures between 24 degrees C and 45 degrees C. 2. Colonic and brain temperatures rose at the higher ambient temperatures; the temperature elevations were no different in pigeons with oesophageal ligation, compared to sham-operated controls. The presence of simultaneous eye covering also had no effect on colonic or brain temperatures. 3. Oesophageal inflation decreased from a rate of 2.8 +/- 1.4 per minute (mean +/- SEM) to zero, in anaesthetized pigeons when warmed from a colonic temperature of 40.5 degrees C to 43.8 degrees C. 4. In pigeons oesophageal inflation plays no significant part in body temperature regulation or in the maintenance of a lower brain than body temperature even in hot ambient conditions. PMID- 2887396 TI - The significance of differences between means. A simulation study. AB - 1. Three tests of statistical significance: the confidence interval (C), Student's t, and Satterthwaite's corrected t were compared using a computer generated sampling experiment. 2. The C-test was shown to be extremely inefficient at detecting differences between pairs of means. The t-test performed as expected and Satterthwaite's correct t was slightly conservative. 3. When the population variances are different Satterthwaite's corrected t performed extremely well, the t-test was slightly liberal, while the C-test remained extremely insensitive. 4. It is concluded that the C-test should not be used (i.e. against Scheer, 1986, Comp. Biochem. Physiol. 83A, 405-408). 5. It is noted that when many t-tests are performed on one data set, alternative methods are appropriate. PMID- 2887397 TI - Relationship between seasonal energy economy and thyroid activity in farm-raised raccoon dogs. AB - 1. The levels of thyroid hormones (T3, T4), total lipids and urea in blood serum of adult farmed raccoon dogs (Nyctereutes procyonoides Gray 1834) were monitored year-round, and compared with seasonal changes in body weight and feed consumption during intense, maintenance and restricted fasting feeding. 2. Thyroid hormone levels tended to be low during winter whereas during the rest of the year no marked seasonal differences were observed. That thyroid hormone levels were influenced by altering feed intake suggests the hypothesis that the winter hypothyroidism observed was a result of a decreased level of voluntary feed intake. 3. The colder the temperature was during winter, the less the animals consumed the feed supplied. 4. Neither season nor feed intake level affected serum levels of total lipids or urea. 5. Marked seasonal changes in body weight of the animals were found. From maximum values occurring in early winter their body weight generally dropped about 30% reaching the minimum values in mid summer. This marked seasonal change was mainly the result of changes in subcutaneous fat reserves. PMID- 2887398 TI - The primary-secondary rumen contraction and gas expulsion in sheep (Ovis aries). AB - 1. Sheep rumens were insufflated with nitrogen to 5, 10, 15 and 20 cm HOH pressure and sustained at each pressure for 5 min. 2. Measurements included rumen motility, reticulorumen myoelectrical activity, eructation frequency and volume, and changes in tracheal pressure. 3. Associated with elevated intrarumen pressure was a previously unreported type of rumen contraction on which gas expulsion occurred, the primary-secondary contraction. 4. Gas expulsion volume was similar on primary-secondary and secondary contractions. 5. The maximum rumen contraction rate per min was 4-5 for secondaries and 1-2 for primary-secondaries. 6. Irrespective of the sustained initial pressure, resting intrarumen pressure was reached within 5 min. PMID- 2887399 TI - Effects of lysine and glutamic acid or [corrected] Mg++ on the conformations of C3 and B, and the activation of the alternative complement pathway. AB - The conversion of C3 and B in the mixture of C3, B, D and Mg++ ions was inhibited in the presence of arginine and lysine, but not in the presence of glutamic acid and aspartic acid among other amino acids. Application of dialyzed plasma to a lysine-Sepharose column resulted in elution of B and a part of D in pass-through fractions, and C3 and the other part of D were retained in the column, subsequently eluted by increase in salt concentrations. C3, B and a part of D were eluted in pass-through fractions, and C3 and the other part of D were retained in the column, subsequently eluted by increase in salt concentrations. C3, B and a part of D were eluted in pass-through fractions when applied to glutamic acid-Sepharose. A highly purified D preparation appeared in the pass through fraction of the lysine-Sepharose column, suggesting that D may form a complex in plasma. The intensity of intrinsic fluorescence of C3 decreased in the presence of arginine to the largest extent. Lysine affected the intensity less than arginine. Kd was calculated to be 0.42 mM for arginine and 0.55 mM for lysine in the interaction with C3. The intensity of intrinsic fluorescence of B decreased in the presence of aspartic acid and glutamic acid (Kd = 0.48 mM for aspartic acid and 0.24 mM for glutamic acid). Arginine or lysine affected the intensity of B less than those anionic amino acids. The presence of Mg++ ions resulted in a decrease in the fluorescence intensity of C3 and B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887400 TI - Metabolic investigations with Femodene--an oral contraceptive containing gestodene and ethinyloestradiol. AB - The metabolic effects of a new oral contraceptive Femodene (SHD 356C) containing 75 micrograms gestodene (delta-15-levonorgestrel) and 30 micrograms ethinyloestradiol were studied in two groups of women. Group 1 consisted of women not currently using oral contraceptives; Group 2 consisted of women switching to Femodene from their current oral contraceptive. Changes in lipid metabolism were assessed by measuring serum levels of cholesterol, triglycerides, LDL-C, VLDL-C, HDL-C, HDL2-C and HDL3-C. Minimal changes occurred in lipid metabolism apart from increases in triglyceride concentrations. Women in Group 1 showed a 105% increase in SHBG levels and a 51% increase in caeruloplasmin levels compared to increases of 33% and 2% in women in Group 2. A comparison of the two groups of women suggested that the gestagen in Femodene exerted a less anti-oestrogenic effect than most of the gestagens currently used in oral contraceptives. No significant changes occurred in liver function (assessed by estimation of gamma-glutamyl transferase) or in the coagulation factors, Factor X and antithrombin III. Minor effects on glucose tolerance as assessed by blood glucose and plasma insulin levels were noted. These minimal effects on metabolism, combined with its high efficacy and acceptability shown in clinical trials, makes Femodene an ideal alternative to currently used oral contraceptives. PMID- 2887401 TI - Microdose intrauterine levonorgestrel for contraception. World Health Organization Special Programme of Research, Development and Research Training in Human Reproduction: Task Force on Intrauterine Devices for Fertility Regulation. AB - An intrauterine device (IUD) releasing 2 micrograms of levonorgestrel per 24 hours was compared in a randomized multicentre clinical trial with two copper IUDs-the TCu 220C and the Nova T. The 2 micrograms levonorgestrel device had statistically significantly higher pregnancy rates (from 390 days of use) and higher expulsion rates (up to 570 days). In addition, the total medical removals and removals for bleeding were significantly higher at all intervals where the data were analysed. Most disturbing was a 6.7 increased relative risk of ectopic pregnancy with the steroid-releasing IUD compared to the combined copper IUD data. It is concluded that the goal of microdose administration of 2 micrograms levonorgestrel to the uterine cavity does not achieve the objectives of a new and improved IUD device which is safe and effective. PMID- 2887402 TI - Localization of the multidrug resistance-associated 170 kDa P-glycoprotein gene to mouse chromosome 5 and to homogeneously staining regions in multidrug resistant mouse cells by in situ hybridization. AB - This report describes the localization of the 170 kDa P-glycoprotein gene(s) to mouse chromosome 5, subbands A2 or A3. Overproduction of P-glycoprotein is associated with multidrug resistance (MDR). MDR cell lines derived from the SEWA mouse tumor carry multiple copies of the P-glycoprotein gene. These were found to reside in homogeneously staining regions, situated in different locations in different sublines. PMID- 2887403 TI - Beta blockers and the sensitivity of the thallium treadmill test. AB - The effect beta blockers (BB) may have on the sensitivity of the thallium treadmill test (Th-TMT) is controversial. The purpose of this study was to test the hypothesis that BB decrease the sensitivity of the Th-TMT. Two hundred three patients over a two-year period were identified who satisfied the following criteria. All had symptom-limited upright treadmill exercise tests with stress and redistribution thallium imaging, as well as coronary angiography within two months of the Th-TMT. Of 58 patients with CAD not on BB, 52 had an abnormal Th TMT scan (sensitivity 90 percent). In comparison, the sensitivity of the Th-TMT scan in the 88 patients with CAD receiving BB was 76 percent (p less than 0.05). We conclude that BB may significantly decrease the sensitivity of the Th-TMT. Physicians should fully appreciate the higher false negative rate (24 vs 10 percent) for patients on BB and consider cautious withdrawal prior to diagnostic studies. PMID- 2887404 TI - Control of postoperative pain. Nonnarcotic and narcotic alternatives and their effect on pulmonary function. PMID- 2887405 TI - Bronchoalveolar lavage in acute hypersensitivity pneumonitis caused by sulfasalazine. AB - Sulfasalazine has been reported to induce pulmonary eosinophilia and hypersensitivity with symptoms of dyspnea and fever. We present the results of bronchoalveolar lavage in a patient with acute sulfasalazine-induced hypersensitivity pneumonitis. The lavage specimen showed a significant influx of eosinophils. PMID- 2887406 TI - [Changes in plasma concentrations of gastrointestinal hormones in patients with liver cirrhosis]. PMID- 2887407 TI - SMS 201-995 improves glucose tolerance in insulin-treated type II diabetic patients. PMID- 2887410 TI - [Genome "dactyloscopy". Characteristics of the human cloned sequence JIN 600 in vector M13 with properties of highly polymorphic DNA marker]. PMID- 2887409 TI - Inhibition of 2-deoxy-glucose-induced glucagon secretion by muscarinic and alpha adrenoceptor blockade in the mouse. AB - Neuroglycopenia induced by 2-deoxy-glucose is known to activate the autonomic nervous system and to stimulate glucagon secretion. In this study, the relative contribution of the various branches of the autonomic nervous system on the 2 deoxy-glucose-induced glucagon secretion was investigated in the mouse. An intravenous injection of 2-deoxy-glucose (500 mg/kg) was followed by a 5-fold increase in plasma levels of glucagon (P less than 0.001). This 2-deoxy-glucose induced glucagon secretion was impaired by pre-treatment with either the muscarinic antagonist methylatropine (by 83%; P less than 0.001) or the nicotinic antagonist hexamethonium (by 90%; P less than 0.001). Further, also the alpha adrenoceptor antagonist phentolamine inhibited the glucagon response to 2-deoxy glucose (by 35%; P less than 0.01). In contrast, the beta-adrenoceptor antagonist L-propranolol did not affect the glucagon response to 2-deoxy-glucose. It is concluded that the main mechanism behind the increased plasma levels of glucagon following administration of 2-deoxy-glucose is cholinergic activation. However, intact alpha-adrenoceptors are a pre-requisite for the full effect of 2-deoxy glucose. In contrast, beta-adrenoceptors seem to be of no importance and there seems to be no room for neuropeptides as mediators of the neuroglycopenia-induced glucagon secretion in the mouse. PMID- 2887408 TI - Mitochondrial changes and associated alterations induced in mice by streptozotocin administered in vivo and in vitro. AB - Isolated mouse liver mitochondria incubated with streptozotocin showed decreased rate and extent of Ca2+ uptake, and, dependent on the concentration of streptozotocin and the addition of alpha-ketoglutarate, glutamate, fluorocitrate or guanosine 5'-triphosphate, the retention of Ca2+ was either increased or decreased. Similar observations were made in liver mitochondria incubated with succinyl-CoA. In mitochondria isolated from the kidneys and islets of mice injected with streptozotocin, with and without additional injections of glucose and/or glucagon, the rate and extent of Ca2+ uptake were reduced and the release of accumulated Ca2+ was stimulated. Electron microscopy and X-ray microanalysis showed dislocation of Ca2+-containing precipitates from the mitochondria to the cytosol, and stereology disclosed increased mitochondrial volume in the B cells of streptozotocin-treated mice. State 3 and state 4 respiration with NAD-linked substrates was inhibited, but succinate oxidation was unaffected, in mitochondria isolated from the kidneys of mice treated with streptozotocin. In the kidneys of streptozotocin-injected mice, the concentration of succinyl-CoA was increased, that of citrate and guanosine 5'-triphosphate was decreased, that of glucose 6 phosphate, fructose 6-phosphate and fructose 1,6-diphosphate was unaffected, and the metabolite concentration ratios suggested increased mitochondrial [NAD+]/[NADH] ratio and decreased cytoplasmic [NAD+]/[NADH] ratio. It is suggested as a new hypothesis that the cytotoxicity and the diabetogenicity of streptozotocin are dependent on inhibited citric acid cycle enzyme activity (primarily that of succinyl-CoA synthetase and citrate synthetase) with altered metabolite concentrations, leading to impairment of the mitochondrial uptake of Ca2+ and the activation of the pyruvate, isocitrate and alpha-ketoglutarate dehydrogenases. PMID- 2887411 TI - [Molecular cloning of genes coding for tumor necrosis factors: tandem localization of alpha and beta genes on the mouse chromosome 17]. PMID- 2887412 TI - Lessening the use of benzodiazepines. PMID- 2887413 TI - Treating infantile asthma in general practice. PMID- 2887414 TI - New topical beta-blockers for glaucoma. PMID- 2887415 TI - [Risk of contrast medium reactions in cardiac diagnosis. Pretreatment with glucocorticoids and antihistaminics in known cases of intolerance to contrast media]. AB - Among 4178 patients who between 1980 and 1986 had undergone left-heart catheterization with left-heart injections and coronary angiography there were 76 (1.8%) with previous reactions to contrast media. These latter patients were given, three days before the planned investigation, 6 alpha-methylprednisolone, 24 mg daily by mouth, and phenhydramine hydrogenmaleinate, 150 mg daily, and two hours before the investigation 80 mg 6 alpha-methylprednisolone hemisuccinate intravenously. The effect of this prophylactic regimen was tested prospectively. Diatrizoate 76% was the contrast medium used. Of 4102 patients without known contrast-medium intolerance 137 (3.34%) had a reaction, 27 of them (0.66%) severe enough to require treatment. Among the 76 patients with known previous reactions, nine (11.8%) had reactions, one very severe requiring treatment, the others mild. The described pre-injection regimen thus allows indicated left-heart contrast medium injection to be undertaken at a justifiable risk. PMID- 2887416 TI - [Unusual side effects of an antidepressive-tranquilizer combination]. PMID- 2887417 TI - Microcirculation and neurotransmitter metabolism in the pathophysiology of brain ischaemia. A role for calcium. AB - Calcium is an essential component in a multitude of cellular processes, ranging from muscle contraction to cell division, and hormone and neurotransmitter release. Disruption of calcium homeostasis at the neuronal level, which occurs in pathological events such as ischaemia, causes a series of biological reactions that ultimately lead to cell death. Furthermore, calcium-triggered events may influence vascular activity, causing spasm at the level of the major vessels and inducing changes in the permeability of the blood-brain barrier. Thus, knowledge of the biochemical events involved in the initiation and progression of cell injury occurring in acute cerebrovascular events may have important implications for possible strategies of pharmacological intervention such as calcium entry blockade. PMID- 2887418 TI - Long term efficacy of a controlled-release formulation of isosorbide 5 mononitrate (Imdur) in angina patients receiving beta-blockers. AB - In a multicentre double-blind crossover study the clinical efficacy and tolerability of a controlled-release formulation, Durules, of isosorbide 5 mononitrate (Imdur) 60mg once daily was compared with placebo over 2 weeks in 70 patients with stable exercise-induced angina pectoris who were receiving concomitant long term beta-blockade. Isosorbide 5-mononitrate significantly improved exercise capacity and signs of myocardial ischaemia, while reducing the number of anginal attacks and consumption of short-acting glyceryl trinitrate tablets compared with beta-blocker therapy alone. During an open follow-up period of 1 year, there was no attenuation of the antianginal efficacy of isosorbide 5 mononitrate. The drug was well tolerated during both phases of the study, and the only significant adverse effect was headache, which rapidly disappeared during continued treatment. PMID- 2887420 TI - Mononitrates in combination with beta-blocker therapy in the treatment of severe angina pectoris. PMID- 2887419 TI - Abrupt withdrawal of isosorbide 5-mononitrate (Imdur) after long term treatment in stable angina pectoris. A preliminary report. AB - 32 patients with stable angina pectoris who had been receiving a controlled release formulation Durules of isosorbide 5-mononitrate (Imdur) 60 to 120 mg daily with concomitant beta-blocker therapy for at least 1 year were entered into a study to evaluate possible rebound phenomena from the abrupt withdrawal of isosorbide 5-mononitrate and to determine whether nitrate tolerance had developed. Isosorbide 5-mononitrate was abruptly withdrawn and substituted with placebo for 2 weeks, after which the active drug was reintroduced. No deterioration of exercise performance could be detected during withdrawal of therapy, but an increase was seen after reinstitution. No tolerance was found for systolic blood pressure and ST segment changes or for the number of anginal attacks and short-acting glyceryl trinitrate tablets consumed. Three patients had to be hospitalised because of a sudden deterioration of symptoms on withdrawal of isosorbide 5-mononitrate. It was concluded that isosorbide 5-mononitrate in Durules has a beneficial effect and that tolerance does not appear to be clinically relevant. PMID- 2887421 TI - gamma-Glutamyltransferase in the newborn. AB - gamma-Glutamyltransferase activity was measured serially in newborn infants. Median activity was 94 units/l, with the 95th centile at 243 units/l. It was unrelated to gestation. Significant increases occurred after treatment with phenobarbitone and with the introduction of oral feeding after parenteral nutrition. It was a poor indicator of total parenteral nutrition (TPN) liver damage. PMID- 2887422 TI - Disappearance of blocking type thyrotropin binding inhibitor immunoglobulin (TBII) during thyroid and steroid medication in a patient with autoimmune thyroiditis. AB - A 55 year-old female had suffered from 3 consecutive diseases for a year. The diseases were ulcerative colitis, primary hypothyroidism and idiopathic thrombocytopenic purpura, and had been treated with L-thyroxine (50 micrograms daily) and betamethasone (0.5 to 1.5 mg daily). On examination, the thyroid gland was not palpable at all, thyroid 99 mTc pertechnetate uptake was 0%, and an echogram revealed the existence of an atrophic gland. Thyrotropin binding inhibitor immunoglobulin (TBII) in the serum was elevated to 58.0% and her IgG almost completely inhibited the in vitro cAMP increase due to bTSH. After 5 months TBII turned out to be negative and the inhibitory IgG activity was reduced significantly. The thyroid gland also became visible scintigraphically. Thyroid medication was then stopped. Four months after the cessation of thyroxine, she felt quite well and her thyroid functions remained within the normal ranges. Antibody to Yersinia enterocolitica was positive at a low titer (X20) in the early stages, but elevated reciprocally with the fall in TBII and finally reached X320. In conclusion, evidence of the disappearance of blocking type TBII from the serum was demonstrated for the first time. Steroid might have caused some favorable effects, and this clinical report indicates the possibility that remission of hypothyroidism due to blocking type TBII can be expected. PMID- 2887423 TI - Effect of thyroid hormone on peroxisomal flavin enzymes in rat liver and kidney. AB - The effect of thyroid hormone on peroxisomal enzyme activity was studied in thyroidectomized- and T4-administered-thyroidectomized rats. In liver, the activities of isozyme A of L-alpha-hydroxyacid oxidase, D-amino acid oxidase, urate oxidase and catalase were decreased by thyroidectomy, and the diminished enzyme activities were restored by T4 administration to rats. These modifications induced by thyroidectomy or by T4 administration, however, were prominent only in immature animals (20-day-old rats). Although the changes in-alpha-hydroxyacid oxidase and D-amino acid oxidase activities, induced by thyroidectomy or by T4 administration, were also observed in 40-day-old rats, those in urate oxidase and catalase activities were not significant in 40-day-old rats. Acyl CoA oxidase activity was not affected by thyroidectomy or by T4 administration in either 20- or 40-day-old rats. In the kidney, isozyme B of L-alpha-hydroxyacid oxidase activity was reduced by thyroidectomy and the diminished enzyme activity was restored by T4 administration in both 20- and 40-day-old rats. D-Amino acid oxidase and catalase activities in kidney, however, were not significantly modified by thyroidectomy or by T4 administration in either 20- or 40-day-old rats. The results suggest that thyroid hormone can modify the peroxisomal enzyme activity, which is prominent in immature animals. PMID- 2887424 TI - Hypersomatostatinemia in chronic renal failure. AB - Plasma concentrations of somatostatin-like immunoreactivity (SLI) were determined in uremic patients on maintenance hemodialysis. Plasma SLI levels were significantly (p less than 0.001) elevated in 26 diabetic uremic patients (67.1 +/- 6.8 pg/ml, mean +/- SE) and in 24 non-diabetic uremic patients (43.5 +/- 7.2 pg/ml), when compared with 60 healthy subjects (5.0 +/- 0.7 pg/ml). Paired pooled plasma from uremic patients before and after hemodialysis was subjected to a reverse-phase octadecasilyl-silica (C-18) cartridge and then the extract was gel filtered on a Sephadex G-25 column (1.6 X 90 cm). Both elution profiles showed two peaks of SLI which coeluted with synthetic somatostatin (SS)-28 and SS-14 markers, respectively. The SS-28-like immunoreactivity (LI) peak, which was estimated by using SS-14 as a reference standard, was 3-fold larger than that for SS-14 LI. On the basis of immunoequivalency of the two components in the present assay, SS-28 LI constitutes approximately 75% of circulating somatostatin. In conclusion, plasma SLI is substantially high in uremic patients of both diabetic and non-diabetic etiology and the SS-28 is a predominant form of circulating SLI in these patients, probably, in part, for a lower clearance of this molecule. PMID- 2887425 TI - Somatostatin suppresses plasma aldosterone concentration in a case of Bartter's syndrome. AB - The study was conducted to examine the effect of somatostatin on activated renin angiotensin-aldosterone system in a case of Bartter's syndrome. After 60 minutes of 500 micrograms of somatostatin infusion, the plasma aldosterone concentration was reduced from the basal level of 250 pg/ml to 140 pg/ml, whereas plasma renin activity remained at the basal level. This result suggests that somatostatin may specifically inhibit aldosterone secretion in Bartter's syndrome and the agent can be applied to a treatment of this syndrome. PMID- 2887426 TI - Neurotransmitter regulation of thyroid activity. PMID- 2887427 TI - The plasma membrane ATPase of the thermoacidophilic archaebacterium Sulfolobus acidocaldarius. Purification and immunological relationships to F1-ATPases. AB - The plasma-membrane-associated ATPase of the thermoacidophilic archaebacterium Sulfolobus acidocaldarius characterized in a previous work [M. Lubben & G. Schafer (1987) Eur. J. Biochem. 164, 533-540] has been solubilized. It can be easily removed from the membrane by mild treatment with zwitterionic detergents, therefore it appears to be a peripheral membrane protein analogous to the soluble F1-ATPase of eubacteria and eukaryotes. Further purification has been achieved by subsequent gel permeation and ion-exchange chromatography. The final purity is greater than 70% as judged by staining intensities after SDS/polyacrylamide gel electrophoresis. The ATPase consists of two major polypeptides of 65 kDa (alpha) and 51 kDa (beta) in comparable quantities; a minor band (20 kDa) is assumed to be a contaminant or a constitutive part of the enzyme, possibly copurified in substoichiometric amount. The native molecular mass of the solubilized ATPase determined by gel permeation is 430 kDa. Considering the precision of these methods, it remains open whether a 3:3 stoichiometry reflects the contribution of alpha and beta subunits to the quaternary structure, in analogy to known F1 ATPases. The catalytic properties resemble those of the membrane-bound state. There are two pH optima at 5.3 and 8.0 in the absence and only one optimum at 6.5 in the presence of the activating anion sulfite. Activity is strictly dependent on the divalent cations Mg2+ or Mn2+. ATP and dATP are hydrolyzed with highest rates; also other purine and pyrimidine nucleotides are cleaved significantly, but not ADP, pyrophosphate and p-nitrophenyl phosphate. The ATPase is insensitive to azide or vanadate but is inhibited by relatively low concentrations of nitrate. Polyclonal antisera have been raised against the beta subunit of the Sulfolobus ATPase. Cross-reactivities with cellular or membrane extracts of a number of archaebacteria, eubacteria and chloroplasts have been analyzed by means of Western blotting and immunodecoration. A strong cross-reactivity with other genera of the Sulfolobales is observed, also with Methanobacterium, Methanosarcina, Methanolobus and Halobacterium. Even membranes of the eubacterium Escherichia coli and of eukaryotic chloroplast react with the antibodies. With one exception, in all cases the molecular mass of the cross-reacting polypeptide falls in the range of 51-56 kDa. Only in Halobacterium halobium, bands at 66 and 68 kDa have been detected. In order to identify the cross-reacting polypeptides, the purified F1-ATPases of E. coli, chloroplasts and beef heart mitochondria have been tested.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2887428 TI - Phenylglyoxal modification of arginines in mammalian D-amino-acid oxidase. AB - The presence of arginine in the active center of D-amino-acid oxidase is well documented although its role has been differently interpreted as being part of the substrate-binding site or the positively charged residue near the N1-C2 = O locus of the flavin coenzyme. To have a better insight into the role of the guanidinium group in D-amino-acid oxidase we have carried out inactivation studies using phenylglyoxal as an arginine-directed reagent. Loss of catalytic activity followed pseudo-first-order kinetics for the apoprotein whereas the holoenzyme showed a biphasic inactivation pattern. Benzoate had no effect on holoenzyme inactivation by phenylglyoxal and the coenzyme analog 8-mercapto-FAD did not provide any additional protection in comparison to the native coenzyme. Spectroscopic experiments indicated that the modified protein is unable to undergo catalysis owing to the loss of coenzyme-binding ability. Analyses of time dependent activity loss versus arginine modification or [14C]phenylglyoxal incorporation showed the presence of one arginine essential for catalysis. The protection exerted by the coenzyme is consistent with the involvement of an active-site arginine in the correct binding of FAD to the protein moiety. Comparative analyses of CNBr fragments obtained from apoenzyme, holoenzyme and the 8-mercapto derivative of D-amino-acid oxidase after reaction with phenylglyoxal did not provide unequivocal identification of the essential arginine residue within the primary structure of the enzyme. However, they suggest that it might be localized in the N-terminal portion of the polypeptide chain and point to a role of phenylglyoxal-modifiable arginine in binding to the adenylate/pyrophosphate moiety of the flavin coenzyme. PMID- 2887430 TI - Randomized factorial trial of high-dose intravenous streptokinase, of oral aspirin and of intravenous heparin in acute myocardial infarction. ISIS (International Studies of Infarct Survival) pilot study. AB - 619 patients with suspected acute myocardial infarction (MI) were randomized to receive either a high-dose short-term intravenous infusion of streptokinase (1.5 MU over one hour) or placebo. Using a '2 X 2 X 2 factorial' design, patients were also randomized to receive either oral aspirin (325 mg on alternate days for 28 days) or placebo, and separately randomized to receive either intravenous heparin (1000 IU h-1 for 48 hours) or no heparin. Streptokinase (SK) was associated with a nonsignificant (NS) increase in non-fatal reinfarction (3.9% SK vs 2.9% placebo) and decrease in mortality (7.5% vs 9.7% in hospital plus 6.1% vs 8.7% after discharge). After SK, there were significantly fewer strokes (0.5% vs 2.4%; 2P less than 0.05), but significantly more minor adverse events (e.g. hypotension and bradycardia, allergies, bruises or minor bleeds, nausea). Aspirin was associated with fewer non-fatal reinfarctions (3.2% aspirin vs 3.9% placebo; NS), deaths (in hospital: 6.1% vs 10.5%; 2P less than 0.05, and after discharge: 7.0% vs 6.9%; NS), and strokes (0.3% vs 2.0%; NS). Heparin was associated with a decrease in reinfarction (2.2% heparin vs 4.9% no heparin; NS), though not in mortality (in hospital: 8.0% vs 8.5%; NS, and after discharge: 7.0% vs 6.9%; NS), and with a trend towards more strokes (1.6% vs 0.7%; NS) and more bruising and bleeding (14% vs 12%; NS). To assess more reliably the effects of aspirin and of this SK regimen on mortality, about 400 hospitals worldwide are now collaborating in a large (about 20,000 patients planned) randomized trial (ISIS-2), for which the present study was a pilot. PMID- 2887429 TI - Some peculiarities of functioning of H+-ATPase from the membranes of the anaerobic bacterium Lactobacillus casei. AB - Radiation inactivation analysis gave the target sizes of 176 +/- 5 kDa and 275 +/ 33 kDa for ATPase from anaerobic Lactobacillus casei and aerobic Micrococcus luteus bacteria respectively. The values are close to the known molecular masses of the enzymes. Thus, to function the L. casei ATPase, like the F1-ATPases, requires a complete structure composed of all the enzyme subunits. L. casei ATPase is inhibited by 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole owing to modification of an amino acid residue(s) with pK greater than 8.5. L. casei ATPase consists of six identical subunits and differs from alpha 3 beta 3 gamma delta epsilon-type F1-ATPases in a number of catalytic properties. Namely, ATP hydrolysis under the 'unisite' conditions proceeds at a relatively high rate suggesting the absence of cooperative interactions between the catalytic sites. Contrary to mitochondrial F1-ATPase. L. casei ATPase does not form an inactive complex with ADP. These findings imply essential differences in the operating mechanism for L. casei ATPase and F1 ATPase. PMID- 2887431 TI - Effects of single oral doses of clobazam, diazepam and lorazepam on performance tasks and memory. AB - The effects on memory and psychomotor performance and the subjective effects of three anxiolytic benzodiazepines (lorazepam 2 mg, diazepam 10 mg and clobazam 20 mg p.o.) have been evaluated in a double-blind, placebo-controlled, cross-over study in 10 healthy volunteers. At each session, measurements were made prior to and +3.5 h after drug administration, except in the case of REY's test, which was presented at H + 1 h (learning) and was evaluated at H + 8 h and at H + 24 h (delayed recall). Single clinical doses of diazepam and lorazepam caused anterograde amnesia by disturbing acquisition, consolidation and retrieval. Clobazam did not impair memory. Lorazepam impaired performances in all the tests used to evaluate perception, immediate memory, reaction time, psychomotor skill and intellectual capacity. Diazepam caused a decrease in cortical arousal and the speed of perception of visual stimuli, whereas clobazam increased reaction time and reduced cortical arousal. Lorazepam caused a significant degradation of performance relative to the other two treatments. PMID- 2887434 TI - Effects of amphetamine analogs on neurotensin concentrations in rat brain. AB - The present study investigates the effects of amphetamine-like analogs on neurotensin systems and compares the same to those of methamphetamine. Like methamphetamine, multiple high doses of each of the analogs examined significantly increased the concentrations of neurotensin-like immunoreactivity in the striatum, substantia nigra and nucleus accumbens; these effects were reversible and specific. The changes in the neurotensin systems developed rapidly and were evident within 6 h following a single administration of two of the analogs studied. PMID- 2887432 TI - Properties of human hepatic UDP-glucuronosyltransferases. Relationship to other inducible enzymes in patients with cholestasis. AB - Glucuronidation of 4-nitrophenol, nopol (a monoterpenoid alcohol) and bilirubin, which in the rat, are catalyzed by three different enzymes, has been examined in liver biopsies from patients with various liver diseases, in particular cholestasis. These different activities were not correlated, which strongly suggests that at least three independently regulated forms of UDP glucuronosyltransferases were present in the microsomes. Non ionic detergents (Triton X100, Emulgen 911) and deoxycholate produced similar activation (more than 2-fold) of the glucuronidation of 4-nitrophenol. Amphipathic substances, such as CHAPS (3-[3-cholamidopropyl-dimethylammonio]-1-propane sulfonate), and lysophosphatidylcholines maximally increased this UDP-glucuronosyltransferase activity, the most potent being oleoyl lysophosphatidylcholine (4-fold increase). Discriminant analysis of the data revealed no correlation between the three different UDP-glucuronosyltransferase activities and the age or sex of the patients. A good correlation was found on multidimensional analysis between form 1 of the enzyme (4-nitrophenol glucuronidation) and, in decreasing order of magnitude, epoxide hydrolase (measured with benzo(a)pyrene-4,5-oxide as substrate), cytochrome P-450, 7-ethoxycoumarin deethylase, aspartate aminotransferase and gamma-glutamyltransferase (r = 0.89); and between Form 3 of the enzyme (bilirubin glucuronidation) and NADPH cytochrome c reductase, alkaline phosphatase, (r = 0.81). These relationships may reflect the differential variation in enzymatic activities in various hepato-biliary diseases. PMID- 2887433 TI - Effects of age on behavioral responses to dopamine agonists in the rat. AB - This study served to examine the differential effects of age (rats aged 2 or 12 months) on behavioral responses induced by bromocriptine and apomorphine. Intraperitoneal (i.p.) injection of bromocriptine or apomorphine produced a lower frequency of yawning responses, in 12-month-old rats than in 2-month-old rats. Apomorphine produced a more pronounced stereotyped behavior in 12-month-old rats than in 2-month-old rats. Apomorphine, at 0.1 mg/kg administered after bromocriptine (1.0-20 mg/kg) potentiated yawning behavior. The frequency of yawning in 2-month-old rats was pronounced at 2.5 mg/kg of bromocriptine but only at 5 mg/kg 12-month-old rats. Apomorphine (0.1 mg/kg) did not produce perioral behavior in 2-month-old rats but did in 12-month-old rats. The apomorphine (1.0 mg/kg)-induced stereotypy was stimulated dose dependently by bromocriptine in 2 month-old-rats but not in 12-month-old rats. Bromocriptine did not produce this behavior when administered alone. Pretreatment of 2-month-old rats with reserpine, a catecholamine depletor, plus alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, inhibited the yawning induced by bromocriptine but potentiated that induced by apomorphine. Such treatment did not significantly alter either bromocriptine or apomorphine-induced yawning responses in 12-month old rats. The apomorphine-induced stereotypy in 2-month-old rats was markedly potentiated by catecholamine depletion but was not affected in 12-month-old rats. These results suggest that the increasing effect on stereotypy and decreasing effects on yawning in the 12-month-old rats seem to result in an alteration of potency and of the ratio of D-2 versus D-1 receptor activity. PMID- 2887435 TI - Discriminative stimulus properties of 8-hydroxy-2-(di-n-propylamino)tetralin (8 OHDPAT): implications for understanding the actions of novel anxiolytics. AB - 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) has effects both characteristic of a serotonin (5-hydroxytryptamine; 5-HT) agonist and antagonist. To investigate the mechanism(s) of action of 8-OHDPAT in vivo, rats were trained to discriminate 8-OHDPAT (0.4 mg/kg) from saline and given various neuroactive compounds during substitution test sessions. Of the 5-HT agonists tested, d-lysergic acid diethylamide, 5-methoxy-n,n-dimethyltryptamine, quipazine, Ru 24969 and 1-(m trifluoromethylphenyl) piperazine did not mimic the training drug; the dopamine agonists apomorphine and SKF 38393 as well as the alpha 2-adrenoceptor agonist clonidine engendered predominantly saline-lever responding. However, the novel anxiolytics buspirone and ipsapirone as well as the ergot derivative lisuride substituted completely for 8-OHDPAT. In combination tests, 5-HT (ketanserin, metergoline, methysergide, pirenperone), dopamine (haloperidol) and norepinephrine antagonists (prazosin, propranolol) failed to attenuate the 8 OHDPAT cue. The similar stimulus properties of 8-OHDPAT and the novel anxiolytics (buspirone, ipsapirone) are mirrored by the common abilities of these agents to selectively inhibit 5-HT1A binding and release punished responding. Thus, the subpopulation of 5-HT1A receptors may mediate the behavioral effects of these compounds in animals and, in turn, the anxiolytic effects of buspirone and ipsapirone in humans. Although not primarily selective for 5-HT, lisuride may also mimic 8-OHDPAT by direct or indirect stimulation of 5-HT1A receptors. PMID- 2887436 TI - Repeated administration of (-)sulpiride and SCH 23390 differentially up-regulate D-1 and D-2 dopamine receptor function in rat mesostriatal areas but not in cortical-limbic brain regions. AB - We studied the possible functional modifications of both D-1 and D-2 dopamine (DA) receptor subtypes following repeated administration of DA antagonists that act selectively on a single class of DA receptors. The functional state of D-1 and D-2 DA receptors in particular was evaluated by measuring SKF 82526 stimulated and bromocriptine-inhibited adenylate cyclase activity in different brain regions of rats treated with saline, SCH 23390, or (-)sulpiride for 21 days. The results indicate that chronic blockade of D-1 DA receptors in striatum, nucleus accumbens, and substantia nigra by SCH 23390 induced up-regulation of the D-1 receptors without changing the functional activity of D-2 receptors. Likewise, chronic blockade of D-2 DA receptors by (-)sulpiride caused up regulation of D-2 but not D-1 DA receptors in striatum, nucleus accumbens, substantia nigra and pituitary. SCH 23390 or (-)sulpiride did not modify the functional activity of either D-1 or D-2 DA receptors located in frontal cortex and hippocampus. In conclusion, these results indicate that chronic treatment with selective D-1 or D-2 DA receptor blockers induces a receptor-specific up regulation which involves the DA receptors located in the nigrostriatal system and pituitary but not those in the limbic-cortical areas. PMID- 2887437 TI - HA autoreceptor assay with superfused slices of rat brain cortex and electrical stimulation. AB - Slices of rat brain cortex previously loaded with [3H]histamine ([3H]HA) via de novo synthesis from [3H]histidine released tritiated histamine ([3H]HA) Ca2+ dependently in a superfused system. Both electrical field stimulation and high levels of K+ ions elicited this release. The extent of release depended on stimulation intensity. Rather strong stimuli, either by high frequency or longer stimulation, were required to elicit sufficient HA release for proper assessment of the concentration-dependence of release inhibition by drugs. The system showed marked depletion (less response per pulse) upon long-continued or successive stimulations. HA added to the superfusion medium inhibited the release evoked by stimulation at frequencies up to 10 Hz or with 30 mM K+ but not the release at higher frequencies or with 45 mM K+. The inhibition was mediated by H3 receptors, was concentration-dependent (pD2 = 7.4) and was complete at 10(-6) M. The H2 agonist impromidine antagonized the inhibition competitively (pA2 = 7.1). It is concluded that this assay in a superfusion system with electrical stimulation is suitable for the assessment of H3 receptor activity of drugs. PMID- 2887438 TI - Somatostatin receptors on cortical neurones and adenohypophysis: comparison between specific binding and adenylate cyclase inhibition. AB - Primary cultures of mouse embryonic neurones from the cerebral cortex and rat pituitary membranes were used to identify and characterize further the somatostatin receptors coupled to an adenylate cyclase and to compare these receptors with specific binding sites for a non-reducible somatostatin analog. 125I-CGP 23996 on both tissues. 125I-CGP 23996 bound specifically to a single population of sites on cortical neurones and pituitary membranes, with a high affinity (Kd = 2.76 and 1.95 nM respectively). The rank order of potency of somatostatin-(1-14) and some analogs (somatostatin-28, [D-Trp8,D Cys14]somatostatin-(1-14), native CGP) to displace 125I-CGP 23996 from its binding sites was similar on both tissues. Furthermore this rank order was also found identical for the inhibition of adenylate cyclase activity on cortical neuronal and pituitary membranes. Finally a good correlation was found between the order of potencies of somatostatin analogs evaluated from binding experiments and adenylate cyclase assays, suggesting the presence of the same receptor observed under two different affinity states. According to the classification of somatostatin receptors by Tran and his colleagues (1985) these results support the hypothesis that SSA is the somatostatin receptor coupled with an adenylate cyclase. PMID- 2887439 TI - Effects of emetine and dehydroemetine at the frog neuromuscular junction. AB - Emetine and dehydroemetine caused concentration-dependent reduction of the quantal content of the endplate potential (EPP) at the frog neuromuscular junction. At lower concentrations, the drugs had presynaptic action only, as they decreased the amplitude of the EPP without significantly affecting that of the spontaneous miniature EPP (MEPP). At higher concentrations, the drugs had postsynaptic effects as well. Studies of low frequency facilitation indicated that although at low concentrations the effect of emetine on quantal content was independent of frequency of stimulation, at higher concentrations the effect became markedly frequency-dependent and many of the stimuli (at 4 and 8 Hz) failed to evoke EPPs. In the voltage-clamped transected cutaneous pectoris muscle emetine (10(-4) M) depressed the peak amplitude of the endplate current (EPC). Emetine markedly shortened the time constant of decay of the EPC (tau) at more negative holding potentials but did not change the single exponential character of the decay. The results indicate that the acute effects of emetine involve blocking neuromuscular transmission by acting prejunctionally at low concentrations and pre- as well as postjunctionally at higher concentrations. The prejunctional effect is due to interference with evoked release and probably, mobilization of acetylcholine. The postjunctional effect is due to blockade of the acetylcholine-activated ionic channel. PMID- 2887440 TI - (+/-)3,4-Methylenedioxymethamphetamine (MDMA) produces long-term reductions in brain 5-hydroxytryptamine in rats. AB - (+/-)3,4-Methylenedioxymethamphetamine (MDMA) was administered to rats as a single 40 mg/kg injection s.c. or 40 mg/kg s.c. every second day for 4 injections. Sixteen days following the last injection rats were killed. MDMA produced significant depletions of 5-HT and its metabolite 5-HIAA in the hippocampus and the frontal cortex. 5-HT was depleted to 30% of control value in the hippocampus following a single dose. 5-HT levels were not affected in the hypothalamus, suggesting differential effects on brain 5-HT systems. DA levels in the hypothalamus were significantly increased while NE levels in the frontal cortex were decreased to 73% of control following 4 doses of MDMA. MDMA, therefore, produces long-term depletions in 5-HT which suggests that it may act as a neurotoxin at 5-HT neurons in the brain of rats. PMID- 2887442 TI - Autoradiographic visualization of binding sites for [3H]somatostatin in the rat brain. AB - [4-3H][Phe6]somatostatin-14 was used to localize somatostatin binding sites in the rat brain by tritium-film autoradiography. The distribution of binding sites using 0.7 nM [3H]somatostatin confirmed that previously described for iodinated tyrosyl analogues of somatostatin, with highest densities of sites in the cerebral cortex (particularly in laminae III-V), amygdala, lateral septal nucleus, hippocampus and claustrum. Investigation of the pharmacological specificity of the binding sites showed that somatostatin-28, but not its N terminal dodecapeptide, somatostatin-28 (1-12) or des Ala1[Gly2,Lys4,Asn5,Thr12,Ser13]somatostatin displaced [3H]somatostatin. Further examination of the binding inhibition characteristics, using a homogenate assay, suggested the presence of two classes of binding sites in the cerebral cortex, hippocampus, midbrain and striatum. The existence of sub-populations of somatostatin binding sites in the rat brain has implications for future studies on the physiological and pharmacological significance of somatostatin receptors in the central nervous system. PMID- 2887441 TI - Intrathecal dynorphins suppress hindlimb electromyographic activity in rats. AB - Intrathecal administration of dynorphin A-(1-17) produced suppression of hindlimb electromyographic activity in rats. This effect was seen also with the [D Ala2]dynorphin (A-(1-17) analog. Intrathecal saline or the prototypical kappa opiate agonist, U50488, did not produce any change in electromyographic activity. These results, along with others, suggest that dynorphin or degradation fragment(s) of dynorphin, induces inhibition of ventral horn output and may possibly have toxic effects on ventral horn cells of the spinal cord. PMID- 2887443 TI - [3H]3,4-methylenedioxymethamphetamine (MDMA) interactions with brain membranes and glass fiber filter paper. AB - The binding of [3H]3,4-methylenedioxymethamphetamine [( 3H]MDMA) to both rat brain membrane preparations and glass fiber filter papers was analyzed in the present study. Saturation studies indicate that [3H]MDMA binding is saturable and monophasic in both the presence and absence of rat brain membranes. This apparent 'specific' binding of [3H]MDMA in both the presence and absence of brain homogenates was totally eliminated by pretreating glass fiber filter papers with polyethylenimine. Drug competition studies demonstrated that [3H]MDMA binding displays a distinct 'pharmacological' profile in the absence of brain tissue. These data indicate that apparent [3H]MDMA binding to rat brain homogenates results from artifactual of [3H]MDMA to glass fiber filter paper. In addition, uptake of [3H]MDMA into rat brain synaptosomes could not be detected. We conclude the [3H]MDMA has limited usefulness in radioligand binding studies. PMID- 2887444 TI - The distribution of beta-adrenoceptors in dog kidney: an autoradiographic analysis. AB - The distribution of beta-adrenoceptors in slide-mounted dog kidney sections was determined using the radioligand (-)-[125I]cyanopindolol ((-)-[125I]CYP) and autoradiography. Using conditions designed to prevent (-)-[125I]CYP binding to non-beta-adrenoceptor sites, biochemical studies revealed that (-)-[125I]CYP binding equilibrated within 150 min (K1 = 3.2 X 10(8) M-1 min-1), was saturable (KD = 30.72 +/- 2.96 pM; Bmax = 0.57 +/- 0.03 fmol/section, n = 4) and stereoselective with respect to the stereoisomers of propranolol and pindolol. Delineation of beta-adrenoceptor subtypes with the selective beta 1-adrenoceptor antagonist betaxolol and beta 2-adrenoceptor antagonist ICI 118,551 demonstrated that the proportions of beta 1-: beta 2-adrenoceptors was between 1:6 and 1:11. Autoradiographic studies showed that beta 1-adrenoceptors were localized on the juxtaglomerular apparatus and glomeruli, while beta 2-adrenoceptors were localized on medullary rays. The distribution of beta-adrenoceptors with respect to renal function in the dog kidney is discussed. PMID- 2887445 TI - Inhibition of renin release by alpha-adrenoceptor stimulation in the isolated perfused rat kidney. AB - The effect of the specific alpha 2-adrenoceptor agonist BHT 933 on stimulated renin release was investigated in the isolated perfused rat kidney preparation. Renin release was stimulated with N-ethylcarboxamide adenosine (NECA) (3 microM) a specific A2-adenosine receptor agonist. alpha 2-Adrenoceptor stimulation with BHT 933 (1 microM) attenuated the stimulation of renin release by NECA. Yohimbine (300 nM) or prazosin (28 nM) at alpha 2- and alpha 1-adrenoceptor specific concentrations respectively, blocked this inhibition of renin release by BHT 933. In all groups studied there was no significant effect of these experimental treatments on renal hemodynamics or electrolyte excretion. The ability of yohimbine or prazosin, at alpha 2- and alpha 1-adrenoceptor specific concentrations respectively, to antagonize the effects of BHT 933 suggests a lack of agonist specificity for these receptor effect as previously suggested for the mesenteric artery. PMID- 2887447 TI - Beta B1 crystallin is an amine-donor substrate for tissue transglutaminase. AB - The effects of tissue transglutaminase on the water-soluble proteins in bovine lens homogenates are described. Addition of liver transglutaminase and Ca2+ to calf lens homogenates resulted not only in the appearance of 50- and 57-kDa dimers, but also in a decrease in the amount of beta B1 crystallin and the almost complete disappearance of beta B3 and beta A3. This is not the result of Ca2+ induced proteolysis, since histamine completely inhibits this phenomenon. It may be concluded that these polypeptides are involved in beta-crystallin crosslinking by transglutaminase. This notion was confirmed by using beta B1- and beta Bp specific antisera. Both sera reacted with the 57-kDa dimer; the beta Bp-specific antiserum also reacted with the 50-kDa dimer. No reaction in the region 50-57 kDa was detectable when EDTA was used instead of Ca2+. Using reconstituted mixtures of beta B1- and beta Bp-crystallin chains, and N-terminally truncated derivatives thereof, it was shown that in the beta B1/beta Bp dimer, glutamine residue -9 of beta Bp crosslinks to one of the lysine residues in the N-terminal extension of beta B1. PMID- 2887446 TI - Effects of potassium and norepinephrine on calcium influx in guinea-pig vas deferens. AB - The effects of potassium (K+) and adrenoceptor agonists on 45Ca influx and contraction of isolated vas deferens from reserpine-treated guinea-pigs has been investigated. K+ (18-84 mM) increased 45Ca influx with the maximum influx occurring at 50 mM K+. The rate of influx upon exposure to K+ was highest in the first 2 min and decreased thereafter. In contrast to K+, norepinephrine, methoxamine and xylazine did not increase the rate of 45Ca influx. Norepinephrine and methoxamine, but not xylazine, inhibited 45Ca influx induced by high K+. The inhibitory effect of norepinephrine was also present in denervated tissues. Prazosin, but not yohimbine or propranolol, blocked the inhibitory effect of norepinephrine. Potassium-induced contractions were significantly potentiated in the presence of norepinephrine, especially at low calcium concentrations. We conclude that K+ contracts the guinea-pig vas deferens by increasing the influx of calcium whereas stimulation of alpha 1-adrenoceptors prevents 45Ca influx elicited by high potassium. PMID- 2887448 TI - Regulation of growth inhibitory activity in transformed mouse embryo fibroblasts. AB - Treatment of the transformed mouse embryo fibroblast cell line AKR-MCA with 1% N,N-dimethylformamide (DMF) resulted in the restoration of a nontransformed phenotype in these cells. In order to determine if an increase in growth inhibitory peptides might be responsible for these changes in growth properties of the DMF-treated AKR-MCA cells we examined the serum-free conditioned medium for its ability to inhibit the anchorage-independent growth of a human colon carcinoma cell line. The extracellular levels of inhibitory activity were two fold higher in conditioned medium derived from AKR-MCA cells than in AKR-MCA cells grown in 1% DMF (AKR-MCA/DMF). Fractionation of the crude conditioned medium indicated the presence of an Mr 20,000 inhibitory fraction in AKR-MCA/DMF conditioned medium which was reduced in AKR-MCA cells. This Mr 20,000 inhibitory activity was acid and heat stable and sensitive to dithiothreitol and trypsin. In addition to inhibiting the growth of a human colon carcinoma cell line this protein induced colony formation in AKR-2B cells and competed for binding to the transforming growth factor beta (TGF-beta) receptor. Therefore, this Mr 20,000 inhibitory polypeptide induced by DMF is probably TGF-beta. TGF-beta was also shown to inhibit the growth of AKR-MCA cells in monolayer culture. PMID- 2887449 TI - Lengths of immunolabeled ciliary microtubules in frog photoreceptor outer segments. AB - Monoclonal anti-tubulin antibodies were used to label microtubules in the connecting cilia and outer segments of retinal photoreceptors isolated from Rana pipiens. In paraformaldehyde-fixed rods from frogs maintained on diurnal light cycles, the anti-tubulin labeling of ciliary microtubules (mean length = 27 micron) typically extends to slightly over half the length of the outer segments (mean length = 46 micron). Rod outer segments from frogs kept in constant darkness for 3-4 weeks are longer (mean length = 53 micron) than rod outer segments from frogs maintained in cyclic lighting. However, the distribution of fractional lengths of anti-tubulin labeling of ciliary microtubules is the same for both lighting regimens. Incubating retinas in 1.0 mM colchicine prior to outer-segment fixation has no effect on the length of immunolabeling of ciliary microtubules, suggesting that post-mortem elongation artifacts are not significant. Incubating retinas in 10 microM taxol prior to fixation significantly increases the length of stained ciliary microtubules, suggesting that taxol either promotes post-mortem assembly of microtubules, or that taxol reduces post-mortem disassembly. The mean position of the end of anti-tubulin labeled ciliary microtubules does not correspond to the position of disk shedding for any of the experimental conditions employed. PMID- 2887450 TI - Neuropeptides TRH and cyclo(His-Pro) share neuromodulatory, but not stimulatory, action on hypothalamic neurons in vitro: implication for the regulation of feeding. AB - Electrical activity of neurons in rat hypothalamic ventromedial nucleus was recorded in tissue slices, to investigate central neural mechanisms underlying reduction of food intake caused by TRH and its metabolite, cyclo(His-Pro) [cHP]. Application of TRH had two actions: stimulation of neuronal activity, which was desensitized on closely repeated applications; and modulation of neuronal responses to neurotransmitters, even in the absence of the stimulatory action. The neuromodulatory but not the direct stimulatory action could also be achieved by cHP. The neuromodulatory action is more likely to be a neural mechanism underlying the inhibition of feeding, while other biological functions, unique to TRH, may depend on direct stimulation. In this way, TRH could achieve different biological results through different modes of action on hypothalamic neurons. PMID- 2887453 TI - Interactions of aminophylline and three benzodiazepine compounds with amygdala kindled seizures in rats. AB - Fully amygdala-kindled rats were used to study the effect of diazepam, RO 15 1788, and CGS-8216 on aminophylline-induced prolongation of elicited kindled afterdischarges. Similar proportional reductions in seizure afterdischarge durations were seen with diazepam and with RO 15-1788 after aminophylline although the absolute length of the afterdischarge durations were increased significantly with both drugs after aminophylline. The partial agonist effect of the benzodiazepine antagonist RO 15-1788 was demonstrated before and after aminophylline pretreatment. However, no specific interaction (pro- or anticonvulsant) was demonstrated with the benzodiazepine antagonist CGS-8216 before or after aminophylline pretreatment. Together these data do not support the theory that the prolongation of elicited kindled seizures by the methylxanthine, aminophylline, is through a specific benzodiazepine receptor mechanism. PMID- 2887452 TI - Dopaminergic cells in the caudal A13 cell group express somatostatin-like immunoreactivity. AB - The caudal extension of the hypothalamic A13 dopamine cell group (A13c) was studied in the rat brain with immunohistochemical techniques using antibodies raised against the dopamine synthesizing enzymes tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC). Adjacent sections revealed that the TH- and AADC-staining patterns exhibited a clear overlap with that for somatostatin (SOM). Employing a double-labelling method with SOM- and AADC antisera and subsequent elution and restaining of the same section with TH antiserum, it was found that all immunoreactivities occurred in the same cell bodies. This study gives the first evidence for the presence of SOM immunoreactivity in dopamine neurons. PMID- 2887451 TI - Somatostatin- and enkephalin-like immunoreactivities are frequently colocalized in neurons in the caudal brain stem of rat. AB - The medulla oblongata and pons of colchicine treated rats were analyzed with a double-staining technique using mouse monoclonal antibodies to somatostatin and rabbit polyclonal antibodies raised against methionine-enkephalin. Numerous cells reacted with both antisera but cells reacting with only one antiserum were also observed. Double-stained cells were most frequently encountered at all levels of the nucleus tractus solitarii, in a well defined group in the caudal medullary reticular formation, along the lateral ventral surface of the medulla oblongata, dorsolateral to the inferior olive and in the nucleus raphe magnus. These findings provide further examples of coexistence of two peptides and indicate the possibility that somatostatin- and enkephalin-like peptides are co-released. PMID- 2887454 TI - Histochemical evidence for the presence of dipeptidylpeptidase IV in the Schwann cells of skin unmyelinated axons. AB - DPP IV activity was localized in the nerve fascicles of cat glabrous skin at light and electron microscope levels. The observation that the DPP IV end product was restricted to the axon-Schwann cell interface suggests that this enzyme may be involved in the interactions between unmyelinated axons and their Schwann cells. PMID- 2887455 TI - Family of Na+,K+-ATPase genes. Intra-individual tissue-specific restriction fragment length polymorphism. AB - Intra-individual tissue-specific restriction fragment length polymorphism (RFLP) has been demonstrated in DNA isolated from different mammalian tissues using cDNAs of alpha- and beta-subunits of Na+,K+-ATPase as hybridization probes. We propose that the RFLPs could result from gene rearrangements in the gene loci for the alpha- and beta-subunits of Na+,K+-ATPase. The changes in restriction patterns have been shown to occur during embryonic development and tumor formation. In addition, the tissue specificity of the expression of different genes of the family of Na+,K+-ATPase genes and their low expression in tumor cells have been demonstrated. PMID- 2887456 TI - Perivenous localisation of Na-dependent glutamate transport in perfused rat liver. AB - Periportal and perivenous hepatocytes differ in their metabolism of blood glutamate (Glu). Uncertainty about the mechanisms of Glu blood-liver exchange led us to characterise, by paired-tracer dilution, a sodium-dependent dicarboxylate transporter (resembling system X-ag) in sinusoidal membranes of perfused rat liver (Vmax = 0.18 mumol Glu/g per min, Km = 0.29 mM Glu). Tracer Glu transport was depressed 65% after necrosis of perivenous hepatocytes by acute CCl4 treatment, indicating that X-ag transporter activity is located mainly in these cells, the sites of glutamine (Gln) synthesis from glutamate and ammonia. Modulation of Glu transport may influence the extent of hepatic Gln release. PMID- 2887457 TI - A prospective study of current diagnostic procedures for assessment of hepatic metastases in colorectal cancers. AB - In a prospective study of 305 patients with colorectal cancers, we assessed the diagnostic value of ultrasonography and laboratory tests. In each case laparotomy was carried out and the presence of liver metastases was established in 47 patients. The results show that the laboratory tests alone are not sufficiently accurate to detect liver metastases. Additional accuracy can be obtained by the combined use of a single liver imaging test (echography) and selected laboratory tests (C.E.A., gamma GT, Alkaline Phosphatase). PMID- 2887458 TI - [Role of calmodulin-dependent reactions in regulating myocardial contractile function]. PMID- 2887459 TI - [Role of endogenous neurohumoral factors in mechanisms of the pathogenesis and compensation of unilateral movement disorders after serial removal of the motor neocortex]. AB - The role of neurohumoral factors in the mechanisms of restoring the lost motor functions after two successive unilateral removals of the neocortex motor region, was studied. The dynamics of the restoring correlated with the posture asymmetry factor (PAF) activity in the CSF. PAF activity was reduced during the restoring by an inactivation factor (FI). Periods of restoration after the 2nd extirpation and inactivation of PAF were shorter than after the 1st one. The existence of the FI before the 2nd extirpation may account for this phenomenon. PMID- 2887460 TI - Activity of some hydrolases in mice with transplantable lymphatic leukemia P 388. AB - Mice--BDF, hybrides, males aged 3 months were injected intraperitoneally with 10(4) lymphatic leukemia cells P 388. The mice were killed by bleeding after 2.5 and 10 days after the injection. Gamma-glutamyltransferase (GGT), leucylaminopeptidase (LAP) and cobalt activated acylase activity were determined in the serum of the mice. The inner organs of the animals were verified histopathologically. A statistically significant increase in the activity of the examined enzymes was observed together with the development of transplantable leukemia. These enzymes can be helpful in early monitoring of lymphatic leukemia P 388 in mice--as markers of cancer growth. PMID- 2887461 TI - Fetal heart rate changes following external cephalic version under tocolysis near term. AB - Fifty eight gravidas near-term underwent external cephalic version using tocolytic treatment and continuous fetal monitoring by cardiotocograph and real time ultrasound. No unfavorable maternal or fetal effects were recorded. Fetal heart rates showed a significant decline at 10 and 30 min after the procedure with complete recovery at 1 h after external version, but no pathologic tracing was recorded. No uniform heart rate patterns due to external cephalic version could be found. PMID- 2887462 TI - Maternal mortality in the Maltese Islands. AB - Maternal mortality statistics from the Maltese Islands since 1935 are reviewed to show that there has been a marked decrease in maternal mortality rates. This decrease is probably related to reductions in family size and improvements in the perinatal care of mothers. Hypertensive disease is now the most important cause of maternal mortality. PMID- 2887463 TI - Serum ferritin levels and their significance in normal full-term pregnant women. AB - Serum ferritin levels were determined by radioimmunoassay (RIA) method and then analysed in 240 normal full-term pregnant women. Their hemoglobin concentrations were found to be normal in the first trimester. None of them had received any hematonic during their whole pregnancy period. Their mean age was 27.7 years and the mean pregnancy duration was 39.5 weeks. Mean hemoglobin concentration in these normal pregnant women was 12.6 g%. Mean serum ferritin was 23.1 ng/ml. It was significantly lower than the mean value of the normal non-pregnant women of the same age. In this study, we found that even normal pregnant women, 15.42% (37 out of the 240) had subclinical iron deficiency and 12.92% (31 out of the 240) of the previously normal pregnant women had clinical anemia during their term of pregnancy. Multiparity was found to be a factor in the prevalence of iron deficiency but age and gravida number played no role in the occurrence of iron deficiency anemia. PMID- 2887464 TI - Hepatitis B vaccine in pregnancy: immunogenicity, safety and transfer of antibodies to infants. AB - To determine the safety and immunogenicity of hepatitis B vaccine in pregnancy, 72 pregnant Nigerians who were negative for markers of hepatitis B virus (HBV) were given two intramuscular doses of vaccine (Heptavax, Merck) in the third trimester. One month after the second dose (at T2), 84% were anti HBs positive. No significant effect was observed in the mothers or their newborns. Passive transfer of anti HBs occurred in 59% of the newborns. The antibodies disappeared rapidly in these infants and by 3 months only 23% had detectable antibodies. No HBsAg carrier status developed in this group. In contrast, the infants born to HbsAg positive mothers had a cummulative rate of HBV events of 20%. It is concluded that HBV vaccine is safe and immunogenic in pregnant females. The passive immunity conferred on the infants is of short duration. Therefore, infants in endemic areas should be vaccinated early, preferably within 3 months of birth. Vaccination of pregnant mothers may provide adequate protection before the child is vaccinated. PMID- 2887465 TI - Sequential radiation changes in cytology of vaginal smears in carcinoma of cervix uteri during radiotherapy. AB - The study deals with acute/immediate radiation changes in 2020 sequential vaginal smears in 101 patients of carcinoma of the cervix uteri, 97 were of squamous cell carcinoma and 4 of adenocarcinoma. The smears were collected after 12-14 days, 15 24 days and 25 days to 6 weeks following radiotherapy. The pretreatment vaginal smears were collected and examined for percentage of cancer cells. Subsequent smears were studied for radiation changes in benign and malignant cells, such as cell size, vacuolation of cytoplasm, multinucleation and nuclear changes, etc. A gradual and linear decline in cancer cells was observed until the end of therapy; 41.6% of patients had less than 10% cancer cells within 12-14 days of therapy, 63.4% of patients between 15 and 24 days and 74.6% after 25 days to 6 weeks following radiation. Eighty three percent of the patients attained zero level at the end of therapy. PMID- 2887466 TI - Ultrasonically guided follicle aspiration for oocyte retrieval in an in vitro fertilization program: further simplification. AB - Transabdominal, transvesical aspiration of oocytes was performed in 58 infertility patients under ultrasound guidance. In contrast to other groups, no particular guiding instruments were used. Wider bore needles and general anesthesia improved the oocyte recovery rate from 44% to 80%, thus approaching the one achieved by laparoscopy. PMID- 2887467 TI - The use effectiveness of the Copper T-200 in Matlab, Bangladesh. AB - Using a unique record keeping system, the use effectiveness of the Copper T-200 is examined in rural Bangladesh. In Matlab the Copper T-200 is a highly effective contraceptive modality. The adopters are typically low to medium parity women under 30 years of age. The most important cause of termination among women in the study was voluntary removal of the device. The complaint most often reported was bleeding followed by pain and weakness. The Matlab experience suggests that sustained motivation and regular resupply are the two key components of this highly successful family planning program. PMID- 2887468 TI - Advanced and unsuspected secondary abdominal pregnancy misdiagnosed before laparotomy. AB - A case of advanced secondary abdominal pregnancy is presented. It happened in a multiparous patient, a heroin addict and with a previous secondary amenorrhea. In spite of having been controlled through the whole pregnancy, the ectopic pregnancy was not diagnosed until a laparotomy was performed, several days after fetal death. After full extraction of the fetus and placenta, followed by left adnexectomy, the postoperatory evolution was normal. Hormonal and echographic studies and fetal monitorings are provided, and the diagnosis and treatment are discussed. PMID- 2887470 TI - Advanced papillary adenocarcinoma of unknown origin as tumor previa during late pregnancy. AB - A 41-year-old woman with advanced abdominal adenocarcinoma presented at term pregnancy. The tumor was presented as previa and obstructed the delivery. A cesarean section was performed and a healthy child was born. At surgery diffuse metastatic disease was detected throughout the pelvis and abdomen and was partially resected. Combined chemotherapy consisting of cis-platinum, adriamycin and cytoxan was administered for 5 months. At second-look laparotomy no residual disease was found. We present an unusual presentation of metastatic abdominal undifferentiated carcinoma treated as ovarian cancer. PMID- 2887469 TI - Antepartal fetal death of one twin. AB - Twenty-four cases with antepartal fetal death of one twin are reported. Of the stillborn fetuses 5 were delivered as a fetus papyraceus, 13 had severe and 6 no maceration. The cesarean section rate was 25%. The placenta was monochorionic in 12 cases. Structural defects were found in one monochorionic co-twin of a fetus papyraceus. Otherwise the neonatal morbidity of the liveborn co-twins was not increased if the low gestational age averaging 34 weeks, was taken into account. No manifestations of defective hemostasis were observed in the mothers. PMID- 2887471 TI - Highly variable minisatellites and DNA fingerprints. PMID- 2887472 TI - Structural-functional organization of hepatic glutamine and ammonium metabolism. PMID- 2887473 TI - Azodisalicylate (azodisal sodium) causes intestinal secretion. Comparative study of the effect of azodisalicylate, sulfasalazine, 5-aminosalicylic acid and sulfapyridine on the water and electrolyte transfer and the morphology of the rat ileum and colon in vivo. AB - Azodisalicylate (ADS) is one of the possible successors of sulfasalazine in the treatment of ulcerative colitis. The following results were obtained when comparing the influence of ADS on net water and electrolyte transfer in tied-off loops of the rat ileum and colon in vivo with sulfsalazine, 5-aminosalicylic acid, and sulfapyridine. (1) Sulfasalazine, 5-aminosalicylic acid and sulfapyridine had no effect on water and electrolyte transfer of the healthy intestinal mucosa in concentrations up to 400 mg%. (2) ADS showed a concentration dependent inhibition effect on net water, sodium and chloride absorption and stimulated secretion at concentrations higher than 100 mg%. (3) No morphological alterations of the mucosa could be observed by light and transmission electron microscopy. The observed effect of ADS might have some clinical significance in patients with a decreased absorptive capacity of the colon in ulcerative colitis, in contrast to healthy volunteers, where the high absorptive capacity of the colon might compensate the decreased absorption or stimulated secretion in the small intestine. PMID- 2887474 TI - Nutritional management of cystic fibrosis. AB - Cystic fibrosis patients have an increased requirement for calories and probably for all the major nutrients. The newer, enteric-coated granular preparations of pancreatic enzyme are more effective than preceding preparations and should permit a normal fat intake. Recent work has emphasized the interdependence of respiratory disease and nutrition. PMID- 2887475 TI - Combination treatment: colloidal bismuth subcitrate with H2-antagonists. AB - A formal single-blind multicentre study has been set up to investigate the probable benefit of combined therapy of the cytoprotective agent De-Nol (colloidal bismuth subcitrate, CBS) and an acid-suppressing drug (cimetidine) in the treatment of duodenal ulcer. The protocol compares the therapeutic benefit of CBS alone and cimetidine alone with CBS + cimetidine, the treatment period being 28 or 56 days. Patients whose ulcers heal within the therapeutic phase will be followed up until relapse or 12 months, whichever is the longer. The paper presented reports interim results from this trial. Comments and clinical observations on the probable value of this combined treatment and the selection of patients suitable for such treatment are discussed. PMID- 2887476 TI - Toxicity of methylenedioxymethamphetamine (MDMA) in the dog and the rat. AB - Methylenedioxymethamphetamine (MDMA) was administered to dogs and rats orally once a day for a 28-day period to evaluate the morphological and neuropathological effects. Major clinical signs associated with the administration of MDMA in the dog included circling, depression, dilated pupils, hyperactivity, rapid breathing, and salivation. Major clinical signs in the rat included hyperactivity, excitability, piloerection, exophthalmos, and salivation. Gross observations at necropsy in the dog possibly related to administration of the test article included reduced testicular size (one high and one medium dose) and prostatic enlargement in two high-dose animals. No gross lesions were seen in the rats at necropsy. The medium- and the high-dose groups in both sexes in both the rats and the dogs gained significantly less weight than the control and low dose groups. Food consumption decreased the first week for the high- and medium dose groups, but a significant reversal toward more normal consumption was noted in the following weeks in both the rats and the dogs. Hematologic, clinical chemistry, and urinalysis values did not appear to be affected by the administration of the test article in the dog. In the rat clinical pathology variables showing a trend to decrease with dose included urinary pH, blood urea nitrogen, glucose, creatinine (females), lactate dehydrogenase (LDH) (females), and chloride. Clinical pathology variables showing a trend to increase with dose included total white blood cell count and phosphorus. Microscopically, testicular atrophy was present in one medium-dose and two high-dose male dogs. Prostatic hyperplasia was present in two high-dose male dogs. No test article-related lesions were seen in the brains of either species. PMID- 2887477 TI - Sympathetic control of cerebral arteries: specialization in receptor type, reserve, affinity, and distribution. AB - The sympathetic neuroeffector system in the mammalian cerebral circulation has a number of distinctive features that reflect its specialized role in this vascular bed: 1) there is limited alpha-adrenoceptor-mediated contraction in large vessels that becomes progressively less important with branching; 2) contraction is limited by receptor number; small branches often seem to have no functional alpha adrenoceptors; 3) adrenoceptor affinity for norepinephrine is low and so is sensitivity; and 4) the dominant alpha-adrenoceptor subtype differs in different species and may have unique characteristics in some. There is a mechanism of non alpha-adrenoceptor-mediated contraction involving low-affinity receptor sites- extraceptors--activated by sympathetic nerves. The pig has a seemingly atypical sympathetic mechanism. On the basis of current information the sympathetic neuroeffector mechanisms of the rabbit seem most clearly related to the human. The size, pattern, and distribution of sympathetic control suggest that the role of the sympathetic nerves is to protect the smaller pial arteries against the consequences of sudden increases in sympathetic adrenal discharge. It is not an important mechanism of controlling cerebral blood flow. PMID- 2887479 TI - Computed tomography as the method of choice in the diagnosis of emphysematous cholecystitis. AB - Computed tomographic (CT) findings in 4 cases of acute emphysematous cholecystitis are described. The use of CT in the diagnosis of this condition is discussed in relation to the use of sonography and plain radiography. PMID- 2887478 TI - Glutathione, a first line of defense against cadmium toxicity. AB - Experimental modulation of cellular glutathione levels has been used to explore the role of glutathione in cadmium toxicity. Mice treated with buthionine sulfoximine [an effective irreversible inhibitor of gamma-glutamylcysteine synthetase (EC 6.3.2.2) that decreases cellular levels of glutathione markedly] were sensitized to the toxic effects of CdCl2. Mice pretreated with a sublethal dose of Cd2+ to induce metallothionein synthesis were not sensitized to Cd2+ by buthionine sulfoximine. Mice sensitized to Cd2+ by buthionine sulfoximine were protected against a lethal dose of Cd2+ by glutathione mono isopropyl ester (L gamma-glutamyl-L-cysteinylglycylisopropyl ester), but not by glutathione. These results are in accord with studies that showed that glutathione mono esters (in contrast to glutathione) are efficiently transported into cells and converted intracellularly to glutathione. The findings indicate that intracellular glutathione functions in protection against Cd2+ toxicity, and that this tripeptide provides a first line of defense against Cd2+ before induction of metallothionein synthesis occurs. The experimental approach used here in which cellular levels of glutathione are decreased or increased seems applicable to investigation of other types of metal toxicity and of other glutathione-dependent biological phenomena. PMID- 2887480 TI - Morphologic and physiologic studies of canine ileal enteroglucagon-containing cells in short-term culture. AB - Enteroglucagon-containing cells have been maintained in short-term culture, and the morphologic characteristics of these cells and their response to selected agents have been determined. After 48 h in culture the ultrastructural appearance of the enteroglucagon-immunoreactive cells showed evidence of polarization with re-formation of apical microvilli and the secretory granules concentrated at the opposite pole of the cell. The size of the intracellular secretory granules was 370 +/- 15 nm. The release of enteroglucagonlike immunoreactivity was stimulated in a dose-dependent manner by the adrenergic agonists epinephrine and isoproterenol. The response to epinephrine was competitively inhibited by propranolol, producing a rightward shift of the dose-responsive curve. The alpha adrenergic agonists methoxamine and clonidine did not stimulate enteroglucagon release above basal. The adenyl cyclase activator forskolin also stimulated release of the peptide in a dose-dependent manner. Carbachol and somatostatin produced a dose-dependent inhibition of epinephrine-stimulated release, indicating direct inhibitory modulation of enteroglucagonlike immunoreactive cells. Somatostatin also inhibited forskolin-stimulated release. These data indicate that canine ileal enteroglucagon cells in short-term culture respond to a number of specific stimuli. PMID- 2887482 TI - Cyclosporine treatment of autoimmune chronic active hepatitis. AB - A 14-yr-old boy with a 5-yr history of autoimmune chronic active hepatitis refractory to corticosteroid therapy was given cyclosporin A (5 mg/kg X day). Before cyclosporine therapy, serum aminotransferase levels were 20 times normal and immunoglobulin G was 4 g/dl. Within 2 wk of starting cyclosporine therapy, aminotransferase levels decreased; by 2 mo they were almost normal, and at 1 yr into therapy they were normal. A decrease in cyclosporine dosage was associated with an increase in aminotransferase levels, which then again decreased as the dose was increased. Severe growth failure observed during previous corticosteroid therapy reversed during cyclosporine treatment and the patient displayed "catch up" growth. No significant side effects were noted after 1 yr of cyclosporine therapy. Further evaluation of cyclosporine in the treatment of corticosteroid unresponsive autoimmune chronic active hepatitis appears warranted. PMID- 2887481 TI - Calcium dependence of neurotensin stimulation of circular colonic muscle of the rabbit. AB - The effect of neurotensin on smooth muscle contraction was compared in strips from rabbit proximal and distal circular colonic muscle. The effective dose for neurotensin stimulation that caused a 50% response in both tissues was similar (1.3 X 10(-10) M). The maximal isometric stress, however, was greater in the distal colon than in the proximal colon (p less than 0.01). Neurotensin stimulation of both proximal and distal colon was unaffected by tetrodotoxin, phentolamine, propranolol, naloxone, or atropine. Neurotensin-stimulated contraction was inhibited by "Ca2+-free" (pCa = 5.1) or La3+ buffer. Verapamil (10(-6) M) or nitroprusside (10(-4) M) decreased neurotensin stimulation of proximal and distal colon by approximately 40% (p less than 0.05). Removal of Ca2+ from the buffer inhibited stimulation of muscle contraction by high extracellular potassium [( K+]o) more than bethanechol stimulation (p less than 0.01). La3+ (1 mM) inhibited the contraction stimulated by bethanechol or increased [K+]o. Although verapamil inhibited contraction by bethanechol and increased [K+]o by approximately 50%, nitroprusside had no effect on the contraction mediated by these stimulants. 8-Bromo-guanosine 3',5'-cyclic monophosphate (cGMP) inhibited neurotensin, but not [K+]o or bethanechol stimulated contraction. These data suggest (a) neurotensin stimulated colonic contractions at a concentration that is potentially physiologic, (b) neurotensin stimulated colonic smooth muscle directly without neural mediation, (c) neurotensin stimulation of colonic muscle is controlled by [Ca2+]o and [cGMP]i. PMID- 2887483 TI - Use of oral antihistamines in dentistry. PMID- 2887484 TI - Production and characterization of antibodies to neuroparsins A and B isolated from the corpora cardiaca of the locust. AB - Antisera were raised in rabbits against neuroparsins A and B which were purified to near homogeneity using electroelution from 7.5% polyacrylamide electrophoresis gels. They were characterized using immunohistochemical, enzyme-linked immunosorbent assay (ELISA), and protein-blotting methods. The antineuroparsin A and the antineuroparsin B sera have different titers and sensitivities (higher titer for antineuroparsin A, higher sensitivity for antineuroparsin B). They exhibit very good specificity. The immunohistochemical study of the entire central nervous system using either antineuroparsin A or antineuroparsin B sera shows that only the A1 type of the protocerebral median neurosecretory cells are immunostained. Moreover, among the numerous proteins of the median region of the brain and of the corpora cardiaca, each immune serum recognized only neuroparsin A or neuroparsin B. Displacement curves obtained for each immune serum by competition between either neuroparsin A or neuroparsin B demonstrate that the neuroparsin A is recognized as well as neuroparsin B, with both antisera supporting the concept that these two proteins are chemically related. The nonspecific binding of neuroparsins to an antisomatostatin immune serum used at 1/100 dilution indicates that any cross-reactivities of invertebrate molecules obtained with very low dilutions of antisera to vertebrate molecules must be considered carefully before concluding any immunological relation between invertebrate and vertebrate products. PMID- 2887487 TI - [Hygienic evaluation of the changes in work capacity of young chess players during training]. PMID- 2887485 TI - A mouse homeo box gene, Hox-1.5, and the morphological locus, Hd, map to within 1 cM on chromosome 6. AB - Mo-10, a homeo box-containing sequence in the Hox-1 complex of genes referred to as Hox-1.5, was found to be polymorphic in inbred and wild mice, and a strain distribution of three allelic forms of Hox-1.5 are reported. The position of Hox 1.5 was mapped in backcross experiments to within 1 cM of the hypodactyly locus on chromosome 6. This identifies the Hd mutation as a useful model for the examination of homeo box expression during mammalian development. PMID- 2887486 TI - [Neuroendocrine and neurochemical mechanisms of the domestication of animals]. AB - A review of experimental data documenting that domestication of animals is associated with hereditary reorganization of neuro-endocrine mechanisms, responsible for basic processes of ontogeny, is presented. The data demonstrated changes in gonadal and pituitary-adrenal systems in domesticated animals. Analysis of evidence that selection for low aggressiveness towards man is, in fact, the selection for definite activity of brain neurotransmitters regulating aggressive behaviour and emotional stress response has been carried out. Supposed role of modifications in the mechanisms of domestication is discussed. PMID- 2887488 TI - [Dynamics of mental work capacity in schoolchildren during the learning process]. PMID- 2887489 TI - Changes in blood flow, portal pressure and shunting during the development of cirrhosis in response to beta-blockade. AB - An experimental model of cirrhosis was developed in the rat to assess the effect of disease and pharmacological manipulation on blood flow, shunting and portal pressure. With progression in the severity of histological cirrhosis there was a steady fall in effective liver blood flow as measured with radioisotope labelled colloid. This corresponded to a rise in portal pressure and shunting with a close correlation between the two (r = 0.7, p less than 0.01). In control animals and when portal hypertension was caused by extrahepatic obstruction, beta-blockade with propranolol, but not selective beta 2 blockade, significantly decreased liver blood flow. With cirrhosis there was a variable response to propranolol depending on the histological severity of disease, the height of portal pressure and degree of shunting. There is a possibility therefore that a potential may exist for lowering portal pressure by manipulating intrahepatic shunting. PMID- 2887490 TI - Immunoglobulin and T cell receptor gene rearrangements in acute leukemias. PMID- 2887491 TI - [Which drugs are allowed, which should one avoid, which are contraindicated?]. PMID- 2887492 TI - [H2 blocker-resistant peptic ulcers. Selection of surgical patients, changes in indications]. PMID- 2887493 TI - [Pain treatment with opiates--a renaissance?]. PMID- 2887494 TI - [Revision of the therapy regimen. Captopril also improves arrhythmia and electrolyte disorders]. PMID- 2887495 TI - [A median attainable therapeutic goal. Living longer and better with disease]. PMID- 2887496 TI - [Therapeutic recommendation in cardiac insufficiency. Initial treatment--after infarct--in kidney disease]. PMID- 2887497 TI - [Advancements in antihypertensive therapy. Single-agent treatment with captopril- diabetic hypertension]. PMID- 2887498 TI - [The manner of rupture in heart insufficiency. ACE-inhibition more as vasodilation--indications]. PMID- 2887499 TI - The costs of AIDS: a review of the estimates. PMID- 2887501 TI - The pancreatic glucagon and C-peptide secretion during hyperinsulinemia in euglycemic glucose clamp with or without somatostatin infusion in normal man. AB - 6 normal subjects received two times of 2 hr euglycemic glucose clamp studies (insulin infusion rate 40 mU/M2/min) one with and the other without somatostatin (SRIF) infusion (500 microgram/hr). Serum C-peptide and glucagon levels were measured during clamp to study the sensitivity of pancreatic alpha and beta cells to the suppressive effects of exogenous hyperinsulinemia during normoglycemia in normal subjects and to find whether SRIF had any modulative effects on endocrine pancreas secretion at the status of hyperinsulinemia. The results showed that in normal man the degree of suppression of pancreatic glucagon secretion by hyperinsulinemia (approximately 100 uU/ml) during euglycemic glucose clamp without SRIF infusion was less than that of C-peptide with mean value of 62 +/- 4% of basal glucagon remained at the end of clamp study; while only about 30 +/- 2% of basal C-peptide concentrations remained. But during SRIF infused glucose clamp studies (SRIF was infused from 60 to 120 min), 32 +/- 2% of mean basal C peptide concentrations and 38 +/- 6% of mean basal glucagon concentrations left at the end of 2 hr clamp studies when serum insulin level was about 100 uU/ml. For the glucose infusion rate (M value), it was significantly greater in our normal subjects in response to insulin + SRIF as compared to insulin alone (12.0 + 0.9 vs 8.8 +/- 1.4; P less than 0.01). We concluded: during hyperinsulinemia (100 uU/ml), the sensitivity of pancreatic alpha cells to insulin seems less than that of beta cells in normal man at normoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887500 TI - The effect of artificial sweetener on insulin secretion. 1. The effect of acesulfame K on insulin secretion in the rat (studies in vivo). AB - Acesulfame K is an artificial sweetener which has been used in the food industry for some years. As yet no metabolic effects have been reported. It was reported that the sweetener can induce a cephalic phase of insulin secretion. To analyse the mechanism of this phenomenon, we studied the effect of Acesulfame K on insulin secretion in vivo. Male Wistar rats, weighing 250-300 g were fasted overnight and anaesthetized with phenobarbital. A silicon catheter was inserted into the right cervical vein for injection of test substances and for obtaining blood samples. In some experiments, another catheter was inserted into the left cervical vein for continuous infusion. Blood samples were drawn at 0, 5, 10, 15, 30 and 60 min after injection, and at -10, 0, 10, 20, 30, 40, 60, 80, 100 and 120 min after the infusion started. Injection of Acesulfame K (150 mg/kg body weight) increased the plasma insulin concentration at 5 min from 27.3 +/- 3.0 microU/ml to 58.6 +/- 4.2 microU/ml without any significant change in the blood glucose. Infusion of Acesulfame K (20 mg/kg body weight/min) for one hour maintained the insulin concentration at a high level (about 85-100 microU/ml) during this period, and at the same time blood glucose was gradually reduced from 103.0 +/- 7.3 to 72.0 +/- 7.2 mg/dl. When using different amounts of Acesulfame K, the insulin secretion was stimulated in a dose-dependent fashion. The effect of Acesulfame K on insulin secretion was similar to that observed by injecting or infusing the same doses of glucose (150 mg/kg) body weight for injection and 20 mg/kg body weight/min for infusion), except that no hyperglycemia was observed with Acesulfame K.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887502 TI - Absence of suppressive effect of somatostatin on prolactin levels in patients with hyperprolactinemia. AB - The effect of somatostatin (SRIF: 10 micrograms/min during 120 min) on serum prolactin (PRL) levels was studied in eleven patients with hyperprolactinemia of varying causes: 2 patients with acromegaly; 2 with primary hypothyroidism; 4 with prolactinoma and 3 with drug (sulpiride) induced hyperprolactinemia. During SRIF infusion, no significant change in PRL levels was observed in any of the 4 groups studied except in one female patient with a prolactinoma. The biological activity of SRIF was demonstrated by the significant inhibition (P less than 0.05) of insulin levels seen in all 11 patients (52% fall in relation to basal) without simultaneous modification of glycemia. These data suggest that SRIF does not decrease PRL secretion in most patients with hyperprolactinemia. PMID- 2887503 TI - The effect of artificial sweetener on insulin secretion. II. Stimulation of insulin release from isolated rat islets by Acesulfame K (in vitro experiments). AB - The effect of the artificial sweetener Acesulfame K on insulin release in vitro was investigated. Pancreatic islets were obtained from Male Wistar rats. Acesulfame K produced a significant increase in insulin release from incubated islets. This effect was dose- and glucose-dependent. When islets were incubated with different amounts of Acesulfame K (2.5, 7.5 and 15 mM) and 15 mM glucose in the media for one hour, insulin concentrations were 140.2 +/- 21.1, 246.7 +/- 32.4 and 313.9 +/- 37.7 microU/ml, respectively. When 15 mM Acesulfame K was added to a media containing 0, 2.5, 5, 10 and 15 mM glucose, insulin release from incubated islets after 60 min were 25.6 +/- 6.4, 65.4 +/- 12.1, 109.0 +/- 10.0, 229.6 +/- 28.0 and 313.9 +/- 37.7 microU/ml. Incubating islets in the media containing arginine or acetylcholine increased insulin release significantly. However, when Acesulfame K was added to the media containing either arginine or acetylcholine, no further potentiating effect could be detected. The effect of Acesulfame K on insulin secretion was decreased by noradrenaline. However, the addition of naloxone, atropine and propranolol had no significant effect. Somatostatin inhibited insulin release from isolated pancreatic islets, but did not antagonize the action of Acesulfame K. When 2.5 mM Acesulfame K was added to a medium containing somatostatin, the inhibitory effect of somatostatin was totally neutralized. In a perifusion system, Acesulfame K stimulated both phases of insulin secretion. In conclusion, Acesulfame K acts directly on the pancreatic islets and potentiates glucose-induced insulin release. PMID- 2887504 TI - Suppression of growth hormone and somatomedin C by long-acting somatostatin analog SMS 201-995 in type I diabetes mellitus. AB - The effect of a new long-acting somatostatin analog SMS 201-995 (SMS) on hormonal mechanisms controlling the glucose metabolism was tested in 8 type I diabetics over a 3-day period. In addition to dietary measures and conventional insulin therapy, the patients received a subcutaneous dose of 50 micrograms SMS three times daily for 3 days. Serum growth hormone (GH) was measured at various intervals throughout the investigational period. Glucagon, somatomedin C (SM-C), triiodothyronine, thyroxine, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) were also determined before and at the end of the therapy with SMS. Basal GH and plasma SM-C had decreased significantly (p less than 0.05 and p less than 0.01, respectively) by the 3rd day. In all cases the insulin requirements could be reduced (mean 28%) without deterioration of the metabolic control. Moreover, blood glucose profiles showed a tendency to lower postprandial peaks after SMS treatment. Glucagon, triiodothyronine, thyroxine, LH, FSH and PRL showed no significant changes. No side effects or alterations in laboratory chemistries were recorded. Dampening of glucose oscillations and counterregulatory mechanisms, and reduction of insulin dosage by SMS may enable a better control of unstable diabetes. Its slow plasma clearance and long action compared to the native peptide will warrant the use of this analog as a additive to standard diabetes therapy in more prolonged trials. PMID- 2887505 TI - Benign oncocytic endocrine tumor of the pancreas in a patient with polyarteritis nodosa. AB - An 8-cm mass in the tail of the pancreas was resected from a 40-year-old man with polyarteritis nodosa. The tumor cells contained abundant, finely granular, eosinophilic cytoplasm arranged in a gyriform pattern that suggested the tumor was an oncocytoma of the endocrine pancreas. Electron microscopy confirmed that the tumor was an oncocytoma by demonstrating tumor cell cytoplasm packed with mitochondria. Ultrastructural and immunocytochemical studies confirmed the neuroendocrine nature of the tumor by demonstrating dense-core, membrane-bound structures consistent with neurosecretory granules and neuron-specific enolase immunoreactivity. No immunoreactivity for insulin, glucagon, gastrin, somatostatin, or pancreatic polypeptide was found. No human chorionic gonadotropin alpha-chain immunoreactivity was detected. The patient is well without evidence of tumor five years after operation. The apparently benign behavior of the pancreatic endocrine oncocytoma reported here is in contrast to the malignant nature of another case reported recently. PMID- 2887507 TI - A model-based self-adjusting two-phase controller for vecuronium-induced muscle relaxation during anesthesia. PMID- 2887508 TI - Physiochemical alteration of surface membrane of axenic Entamoeba histolytica during repeated cholesterol passage. PMID- 2887506 TI - Familial hypercholesterolemia in South African Afrikaners. PvuII and StuI DNA polymorphisms in the LDL-receptor gene consistent with a predominating founder gene effect. AB - Familial hypercholesterolemia (FH), at a prevalence of more than 1 in 100, is at least five times more common in one South African population group than in populations in North America and Europe. Fourteen homozygotic familial hypercholesterolemic subjects from this South African group were genotyped for two intragenic DNA restriction fragment length polymorphisms (RFLPs) in the LDL receptor gene. A StuI polymorphism is located in exon 8, and a PvuII polymorphism, in intron 15. Of ten unrelated FH homozygotes genotyped for both RFLPs, nine were homozygous for an S + P- haplotype, and one was heterozygous for an S + P-/S-P + haplotype. The remaining four were genotyped for PvuII only and were homozygous for P-. Compared with a previously determined population frequency for the latter, this represents an association (P less than 0.05) between the frequency for the P- allele and FH in this population, and this finding is consistent with the "founder gene effect" previously postulated to be present on genealogical and biochemical evidence. PMID- 2887509 TI - Elicitation of protective immunity to Entamoeba histolytica--an experimental study. AB - Immunization of hamsters with plasma membrane (PM) antigens of virulent subline of axenic Entamoeba histolytica (NIH: 200 V) entrapped in multilamellar phosphatidyl choline liposomes conferred 100% protection to a subsequent intrahepatic amoebic challenge. In contrast, vaccination of hamsters with live amoebic trophozoites injected intradermally failed to protect any of the animals. The protected animals had significantly high levels of anti-PM anti-amoebic antibodies, cellular sensitization and macrophage-mediated antibody-dependent cytotoxicity against amoebic trophozoites. However, none of the intradermally immunized animals had anti-PM anti-amoebic antibodies at the time of challenge. Such animals also had significantly low macrophage-mediated antibody-dependent cellular cytotoxicity. The data indicate the potential prophylactic use of PM antigens against hepatic amoebic infection. PMID- 2887510 TI - [Oxatomide in the treatment of chronic urticaria: evaluation of its effectiveness and tolerance]. PMID- 2887511 TI - Differences in Ly 2- L3T4- thymocytes from foetal and adult murine thymus. AB - The thymus is the major site of mammalian T cell production. The exact steps which occur in the thymus and give rise to mature T cells have not been defined, but there is general agreement that the earliest T cells are included in the group of thymic lymphoid cells lacking Ly 2 (CD8) and L3T4 (CD4). This population represents 2-6% of adult thymocytes and the vast majority of thymocytes in the mouse embryo until about day 16 of gestation. It has often been assumed that the foetal and adult CD4- CD8- thymocytes are equivalent. This paper shows that there are significant differences between the CD4- CD8- cells from these sources, in that the adult includes at least two subsets which are undetectable in the embryo. These two subsets of CD4- CD8- cells are both Ly 1high, B2A2- and M1/69-; one is Thy 1+ and one is Thy 1-. Each represents 20-25% of adult CBA double negative thymocytes. Both these populations are excluded from analyses of CD4- CD8- thymocytes which have been further selected as Ly 1low, a procedure adopted in several studies of early thymocytes. Even those subpopulations of CD4- CD8- cells which appear to express similar markers in adult and embryo thymus are quite different when analysed for cell size (forward light scatter), with the embryonic forms being much larger. PMID- 2887512 TI - Evidence for a new murine immunoglobulin heavy chain variable region gene family. AB - In the course of a previous study addressing autoantibody generation in murine models for generalized autoimmune disorders, we observed a nonfunctional immunoglobulin heavy chain transcript in a B cell hybridoma from lupus-prone MRL Mp-lpr/lpr mice. This transcript, the cDNA sequence of which is presented here, is of general interest for murine immunoglobulin genetics as it cannot be ascribed to any known heavy chain variable region gene (Vh) family by nucleic acid sequence homology criteria and, hence, may represent a new Vh gene family. The sequence showed about equal nucleotide similarity (70-73%) to 3 other Vh gene families (S107, J606, 7183) and less than 65% similarity to members of the remaining 6 Vh gene families. Nucleic acid sequence comparisons with unpublished immunoglobulin sequences uncovered a highly homologous (greater than 95%) functional Vh transcript indicating that the suggested Vh gene family also encodes expressed antibody molecules. PMID- 2887513 TI - Major fragment of soluble peptidoglycan released from growing Bordetella pertussis is tracheal cytotoxin. AB - Bordetella pertussis is known to release a factor which promotes the loss of ciliated respiratory epithelium and copurifies with a soluble peptidoglycan (PG) fragment termed tracheal cytotoxin (TCT). The objective of this study was to determine whether pertussis organisms turn over and release PG derivatives in addition to TCT. B. pertussis Tohama (phase III) was grown in liquid Stainer Scholte medium containing [3H]diaminopimelic acid (DAP) to label PG specifically, washed to remove free label, and suspended in fresh medium without [3H]DAP. Molecular sieve chromatography of supernatants obtained from such cultures revealed a single included peak of 3H, the elution volume of which corresponded roughly to a disaccharide peptide monomer standard (ca. 10(3) daltons). This material (i) contained [3H]DAP in acid-hydrolyzable linkage, (ii) comigrated with 1,6-anhydro-N-acetylmuramic acid-containing disaccharide peptides on paper chromatography, (iii) was resistant to degradation by mild alkali, and (iv) was indistinguishable from authentic TCT by high-voltage paper electrophoresis and two reversed-phase high-performance liquid chromatography systems. Together, the data suggest that B. pertussis releases a markedly homogeneous set of PG fragments, consisting principally of TCT, and that TCT is possibly a nonreducing, anhydromuramic acid-containing fragment or a cyclic PG derivative. PMID- 2887514 TI - Use of bronchoalveolar lavage to compare local pulmonary immunity with the systemic immune response of Toxocara canis-infected mice. AB - Following infection of mice with larvae of the canine roundworm Toxocara canis, there is a persistent pneumonitis. Heretofore, nothing was known about the immunologic potential of the cells that constitute this inflammatory exudate. By performing bronchoalveolar lavage (BAL), enough inflammatory cells were obtained to compare the local pulmonary immune response to T. canis infection with the systemic immune response as reflected in the peripheral blood and spleen cells of the same mice. Groups of C57BL/6J female mice were given 100 infective ova and BAL, peripheral blood, and spleen cells collected on days 8, 11, 14, and 17 postinfection. The percentage of eosinophils in the BAL averaged about 80% and was four to five times as great as that in the peripheral blood at all times assayed. Use of concanavalin A (ConA)-elicited lymphocyte blastogenesis to evaluate T-lymphocyte activity revealed that BAL T-cell activity was low on day 8 and peaked on day 11. When the B-cell mitogen lipopolysaccharide was used in the assay, there appeared to be far less BAL cell reactivity compared with BAL T-cell activity. Both B- and T-cell responses of the BAL cells were only a fraction of the responses seen concurrently in spleen cells. Use of Toxocara exoantigens in the blastogenesis assay revealed that Toxocara exoantigens could elicit between 20 and 95% of the ConA response in BAL cells, while in spleen cells Toxocara exoantigens could only elicit 1 to 5% of the ConA response. These results suggest that BAL is a useful method for recovering local inflammatory cells that possess detectable immunologic activity. In the case of pulmonary toxocariasis, eosinophils account for the majority of the cells that are present, with most of the remaining cells being T. canis antigen-specific T lymphocytes. PMID- 2887515 TI - Serological response to the P fimbriae of uropathogenic Escherichia coli in pyelonephritis. AB - Uropathogenic Escherichia coli strains isolated from four patients with pyelonephritis were characterized by their O:K serotype, hemolysin production, mannose-resistant hemagglutination, and the serotype of the P fimbriae. These P fimbriae were serotyped with specific monoclonal antibodies. Serum samples from the patients were analyzed for the presence of specific antibodies to the P fimbriae. In all cases antifimbrial antibodies were found, strongly suggesting that these P fimbriae are expressed in vivo. However, the antibodies in the patient sera were not able to inhibit the mannose-resistant hemagglutination. This finding suggests that these antibodies react with the fimbrial components and not with the minor components which are responsible for adhesion. PMID- 2887517 TI - Reduction of fear and anxiety in adult fearful patients. AB - Dental fear is most often of multifactorial origin and is most successfully treated by behavioural therapies. The need for specialized treatments is related to the severity of the fear reaction and its consequences. For the majority of anxious patients simple treatment techniques readily available and applicable in general practice should be used. These procedures aim to restructure the patient's anticipation and evaluation of the dental situation. However, the establishment of specialized research and treatment centres has resulted in improved understanding and knowledge of the severely phobic patients with long standing avoidance symptoms. These individuals suffer from more disseminated effects of dental fear and benefit most from broadly based therapies that use both cognitive-behavioural and psychophysiological components. There may also be indications for the use of pharmacological therapies. The immediate posttherapy successful outcome rates are at levels of 70 to 80 per cent for broadly based therapies or combinations of treatment modalities. In spite of an obvious shortage of follow-up investigations, Swedish studies on severely phobic and avoiding groups have revealed that similar outcome figures may be valid over longer periods of time. The Swedish studies also indicate beneficial side-effects on the patients' general well-being and psychosocial situation. PMID- 2887516 TI - Plasmid-mediated surface fibrillae of Yersinia pseudotuberculosis and Yersinia enterocolitica: relationship to the outer membrane protein YOP1 and possible importance for pathogenesis. AB - The cell surface properties of Yersinia pseudotuberculosis and Yersinia enterocolitica mutants, constructed by insertional inactivation of genes located on the 40- to 50-megadalton virulence plasmid, were examined. Electron microscopy revealed an absolute correlation between expression of four plasmid-dependent, temperature-inducible properties related to the bacterial surface: (i) a fibrillar matrix covering the outer membrane, (ii) outer membrane protein YOP1, (iii) spontaneous autoagglutination, and (iv) mannose-resistant hemagglutination of guinea pig erythrocytes. Immunoelectron microscopy indicated that YOP1 is a structural component of the fibrillae. Experiments demonstrating inhibition of hemagglutination by anti-YOP1 monoclonal antibody suggested a potential role for YOP1 in adhesion. Insertional inactivation of the gene coding for YOP1, with resultant loss of the ability to express fibrillae, led to a significant reduction in the capacity of Y. enterocolitica, but not Y. pseudotuberculosis, to colonize the ileum of orogastrically infected mice. In both Y. enterocolitica and Y. pseudotuberculosis, inactivation of the genes coding for Ca2+ dependency reduced the ability to maintain intestinal colonization, regardless of the ability to express fibrillae. Both surface fibrillae and Ca2+ dependency seem to reflect pathogenic determinants which are required for the establishment of Y. enterocolitica infection. In Y. pseudotuberculosis, however, no clinical significance of the fibrillae has so far been defined. PMID- 2887518 TI - Protection of cynomolgus monkeys against infection by human T-cell leukemia virus type-I by immunization with viral env gene products produced in Escherichia coli. AB - Protection against human T-cell leukemia virus type-I (HTLV-I) infection in cynomolgus monkeys, achieved by immunizing the animals with env gene products of HTLV-I produced in Escherichia coli, was evaluated. Four monkeys that had been immunized with the env product produced antibody against HTLV-I gp68 and gp46, and their sera were found to cause strong inhibition of syncytium formation of a cat fibroblast cell line induced by HTLV-I. Immunized and non-immunized monkeys were challenged with live MT-2 cells, a high HTLV-I-producer cell line. After challenge, all the control non-immunized monkeys were infected with HTLV-I, as judged by the frequent detection of HTLV-I-antigens in cultures of their peripheral blood mononuclear cells (PBMC), whereas no antigens were recovered from PBMC of immunized monkeys. These results indicate that humoral immunity against HTLV-I-envelope protein elicited by immunization with the polypeptides synthesized in bacteria protected the monkeys against primary infection with HTLV I. PMID- 2887519 TI - Comparative effects of beta-, alpha- and combined beta- plus alpha-adrenoceptor blocking agents in stress-induced increase in arterial blood pressure. AB - Comparative efficacy of cardioselective beta-adrenoceptor blocker (atenolol), non cardioselective beta-adrenoceptor blocker (propranolol), alpha-adrenoceptor blocker (prazosin) and combined alpha plus beta-adrenoceptor blocking agent (labetalol) on cold stress and hand grip exercise-induced increase in arterial blood pressure and heart rate was studied in 7 healthy volunteers. The design of the trial was controlled, randomized, double blind and crossover. All the 4 drugs produced a fall in both supine and sitting systolic as well as diastolic blood pressure. Basal heart rate was reduced by propranolol and atenolol whereas prazosin and labetalol did not produce any change. The increase in both systolic and diastolic blood pressure induced by cold stress was significantly (p less than 0.01) reduced by labetalol, prazosin and atenolol in the decreasing order of efficacy. The increase in systolic blood pressure due to hand grip exercise was reduced significantly (p less than 0.05) by all the 4 drugs and the most effective drug was labetalol. However, the increase in diastolic blood pressure due to hand grip exercise was not reduced significantly by any of the drugs. Therefore, combined alpha and beta-receptor antagonist is more effective in reducing the spikes of blood pressure rise due to these stressful conditions as compared to pure alpha or beta-adrenoceptor antagonists. PMID- 2887520 TI - Double-blind comparison of once-daily bopindolol and atenolol for mild-to moderate hypertension. AB - In order to compare the medium term antihypertensive effectiveness and tolerability of atenolol with those of bopindolol (LT 31-200), a new non selective beta-blocker with slight PAA (partial agonist activity), a randomized double-blind study was performed. Thirty-one outpatients with mild-to-moderate essential hypertension (WHO stage I-II) were enrolled and after a placebo run-in randomly allocated to bopindolol (1 to 4 mg/day) or atenolol (50 to 200 mg/day). The dose was titrated according to the individual pressor responses, and thereafter it was kept constant until the end of the treatment (12 weeks). Both drugs induced statistically significant decreases in SBP, DBP and HR, both in resting conditions and during an ergometric test. Accordingly, most patients achieved the main goal of the therapy, i.e., supDBP less than or equal to 90 mmHg, 11/15 (74%) with bopindolol versus 8/13 (62%) with atenolol. There were no significant differences between the effects of the two compounds. Resting airway resistance (expressed as Peak Expiratory Flow) was not influenced by the treatments. The antihypertensive efficacy was still evident after 12 months in 8 patients who were evaluated for non-comparative long-term effectiveness of bopindolol monotherapy, and improvements in plasma lipid profiles were also observed. Side effects were relatively mild and transient, with two patients in the atenolol group discontinuing therapy (one for inefficacy and one because of undesirable reactions) and one dropped out in the bopindolol group (late evidence of not fulfilling inclusion criteria).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887522 TI - Ureaplasma urealyticum in semen for artificial insemination. PMID- 2887521 TI - An HPLC assay for sulphapyridine in plasma and its use to assess small bowel transit time after the administration of sulphasalazine. AB - An HPLC assay for sulphapyridine is described. The use of the assay to measure sulphapyridine produced by the action of large bowel flora on 2 g of orally administered sulphasalazine as a means of assessing oro-colonic transit time is discussed. The assay is applied to show the action on oro-colonic transit time of a novel gastrokinetic agent BRL 24924 which brought about a 62.8% median reduction in transit time at a dose of 5 mg. PMID- 2887523 TI - Generic drugs in reproductive medicine: is the value anticipated the value obtained? PMID- 2887525 TI - Mast cells and idiopathic male infertility. AB - Eighty-three testicular biopsies, done for evaluation of oligozoospermia and azoospermia, were reviewed. Biopsies from eight healthy fertile males served as control. Johnsen's scoring was used for the staging of spermatogenesis. The number of mast cells was counted in a 1-mm2 area to study the relationship of spermatogenesis and mast cell proliferation. An impairment of spermatogenesis was noticed as the mast cell density increased. When the Johnsen score ranged between 1 and 4, mast cells were 24 to 112, with a mean of 57.7 cells/mm2. This value was highly significant when compared with control cases (P less than .001). PMID- 2887524 TI - Removal of completely perforating IUDs by explorative laparotomy. AB - Nine patients with completely perforating intrauterine contraceptive devices are presented. In all cases, the device was removed by explorative laparotomy. In eight out of the nine women, the device was found to be embedded in the omentum or vesical peritoneal plica. The advantages of explorative laparotomy over laparoscopy or colpotomy are emphasized. PMID- 2887526 TI - Long-acting agonists of LH-RH in the treatment of large ovarian endometriomas. AB - Reversible temporary medical oophorectomy using long-acting agonist analogs of LH RH was tried in three infertile patients suffering from large endometriomas of the ovary. These patients had stage IV disease according to the revised 1985 classification of the American Fertility Society. D-Ala6-des-Gly10-LH-RH propylamide (D-Ala6-LH-RH PA), in a dose of 125 micrograms, was administered intramuscularly every 48 hours to one patient, and daily to the other two patients, for 22, 17, and 14 weeks, respectively. Two patients subsequently received 100 micrograms of D-Trp6-LH-RH for 4 weeks in order to compare its efficacy with D-Ala6-LH-RH PA. Clinical controls, pelvic ultrasonography, and routine laboratory tests and hormone assays were done periodically. Ultrasonography images showed a reduction in the size of endometriomas after the second or third week of treatment. This reduction was maintained throughout and continued after the period of treatment. Suppression of the pituitary and estrogen responses was obtained rapidly, but some transient increments were occasionally found. Progesterone levels always decreased and remained in the range of the early follicular phase. Most intervals of uterine bleeding were prolonged. An evident improvement of abdominal pain, dysmenorrhea, and dyspareunia was found. Administration of D-Trp6-LH-RH was more effective than D Ala6-LH-RH PA in most of the parameters tested. After discontinuation of treatment, all three patients had a prolonged follicular phase with a normal luteal phase during the first cycle. One woman became pregnant in the fourth cycle after discontinuation of D-Ala6-LH-RH PA and delivered a normal baby.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887527 TI - Bacterial infection of human oocytes during in vitro fertilization. PMID- 2887528 TI - Testing the fertilizing ability of motile spermatozoa separated by Percoll in patients with abnormal sperm analysis or sperm penetration. AB - The Percoll density-gradient technique was used to select motile sperm from men who exhibited abnormal semen analysis or unexplained infertility. The fertilizing ability of the spermatozoa was evaluated by the hamster ova sperm penetration assay (SPA). The current work is a novel approach in the usage of Percoll in an attempt to improve the quality of the sperm of nonfertile patients and to examine its results by SPA. The method succeeded in improving the penetration score of the fertile controls by 15% to 30%. However, no improvement of the low penetration score of the nonfertile patients was demonstrable. The difficulties inherent in using the Percoll density gradient technique are discussed. PMID- 2887529 TI - The effects of mesterolone on sperm count in idiopathic oligospermia. AB - Forty subfertile men with idiopathic oligospermia were randomly treated with mesterolone or with placebo for more than 4 months. Seminal analysis was performed thrice before treatment, and twice after 16 weeks of treatment. There was a significant increase of semen volume (P less than .05), mean sperm concentration (P less than .01), and mean total sperm count per ejaculate (P less than .01) with mesterolone therapy. Sperm motility and morphological characteristics were not modified by mesterolone therapy. Mesterolone was found to be effective in improving the sperm concentration in mild and moderate rather than in severe idiopathic oligospermia. PMID- 2887530 TI - Local autoimmunity in mild endometriosis. AB - Forty-four patients with and without mild endometriosis were tested for the presence in peritoneal fluid of autoantibodies against endometrial and ovarian antigens. Five patients with endometriosis and one patient in the control group had significantly elevated titers, and the mean of titers was similar in each group. These results suggest that local autoimmunity is not a likely phenomenon in patients with mild endometriosis. PMID- 2887532 TI - Bilateral functioning uterine anlagen with the Rokitansky-Mayer-Kuster-Hauser syndrome. AB - This report describes an adolescent female with a shallow vaginal pouch and bilateral functioning uterine anlagen, who presented with cyclic pelvic pain and a pelvic mass. Removal of both functioning uterine anlagen afforded complete relief of symptoms. PMID- 2887531 TI - Ovulation induction by human menopausal gonadotropin with ultrasonic monitoring of the ovarian follicles. AB - One hundred sixteen cycles of human menopausal gonadotropin (hMG) treatment for ovulation induction were studied. The ovarian response to hMG treatment was monitored by the daily determination of serum estradiol (E2) or by daily serum E2 and repeated ultrasonic examination of the ovaries. There were more follicles 18 mm in diameter or larger at the time of human chorionic gonadotropin (hCG) administration in the pregnancy than in the non-pregnancy cycles, and in the hyperstimulated than in the nonhyperstimulated cycles. The ovulatory rate and the pregnancy rate per cycle did not improve with the use of ultrasound. The number of treatment cycles required to achieve pregnancy was less in patients who had ultrasonic examination of the ovarian follicles. These results suggest that ultrasonic examination of the ovarian follicle helps to reduce the number of hMG cycles required to achieve pregnancy. The development of multiple follicles results in more pregnancies. However, the use of ultrasound does not improve the pregnancy rate. PMID- 2887533 TI - Effect of 22,25-diazacholesterol dihydrochloride on the spermatogenesis of a wild rat, Bandicota bengalensis. AB - The effects of 22,25-diazacholesterol dihydrochloride (SC-12937) on the spermatogenesis of the bandicoot rat (Bandicota bengalenesis), heretofore unreported on any mammalian species, were studied. Rats were given a single subcutaneous injection of SC-12937 at a dosage of 100 or 200 mg/kg body weight and were killed on days 2 or 10 post-injection. Quantitative analysis of the germinal epithelium was performed on testicular sections (5 micron) stained with periodic acid-Schiff-hematoxylin to assess spermatogenesis. Treatment with SC 12937 at both dosages was found to interfere with the spermatogenic process of this pest rat. In addition to its antispermatogenic action, at higher dosage (200 mg/kg), this compound produced a marked suppression in accessory organ function. The results indicate that a single administration of SC-12937 in low dosage can cause spermatogenic inhibition without affecting accessory organ function in the bandicoot rat. PMID- 2887534 TI - Epididymal ligaments: anatomy and function. AB - Three ligaments are described in relation to the epididymis: superior and inferior epididymal, and vasal ligaments. The study was conducted on 38 cadavers and included direct dissection and histologic examination. The superior and inferior epididymal ligaments are triangular folds of the visceral tunica vaginalis, and extend from epididymis to testicle. The superior ligament binds the epididymal head to the testicle, protecting the fine efferent ductules from damage. The inferior ligament fixes body and tail and mesoepididymis; further, it prevents epididymal convolutions from unraveling. The vasal ligament is a fibrous band, which binds the proximal end of the vas to the epididymal tail. It maintains an acute epididymovasal angle. In two cadavers, the inferior epididymal and vasal ligaments were absent. Convolutions of the lower body and tail of the epididymis were unraveled. The mesoepididymis was broad, and the epididymis was freely mobile from side to side; the epididymo-vasal angle was opened. The role of the epididymal and vasal ligaments in fixation of the epididymis, preservation of blood supply to both testicle and epididymis, and preventing unraveling of epididymal convolutions is stressed. Absent epididymal ligaments lead to "mobile epididymis," which may cause infertility. PMID- 2887535 TI - Value of a single intraperitoneal dose of heparin in prevention of adhesion formation: an experimental evaluation in rats. AB - The effect of a single dose of intraperitoneal heparin on postoperative adhesion formation was examined in the rat. Seventy-two rats were divided into two groups. Trauma was produced with a brush in one group, and by transection of one uterine horn followed by microsurgical reanastomosis in the second group. Single doses of intraperitoneal and subcutaneous heparin were compared, with respect to adhesion formation, with a similarly administered dose of normal saline. A beneficial effect in reducing adhesion formation was demonstrated with intraperitoneal heparin. The effect was more pronounced after microsurgical anastomosis. No harmful effect on haemostasis or wound healing was observed. In view of the adverse effect of postoperative adhesions on the result of infertility surgery, we suggest that the use of intraperitoneal heparin in the human should receive serious consideration. PMID- 2887536 TI - Hybridization and partial cDNA sequence analyses of bovine lung angiotensin I converting enzyme. AB - The mRNA encoding angiotensin I-converting enzyme, a zinc-metallo dipeptidyl carboxyhydrolase, has been identified in extracts prepared from bovine lung tissue. Bovine lung poly(A) + mRNAs were subjected to electrophoresis and northern blot hybridization analysis using a radiolabeled synthetic 24 deoxyoligonucleotide probe complementary to eight codons for amino acids at the active-site of the enzyme (Harris, R.B. & Wilson, I.B., J. Biol. Chem. 260, 2208 2211, 1985). This amino acid sequence contains the catalytic glutamic acid residue. A single RNA species (approximately equal to 4 kb) was detected which is 1 kb larger than predicted from the molecular weight of the enzyme. The excess nucleic acid composition may be due to leader and/or trailer sequences or the RNA may encode a high molecular weight precursor form of the enzyme. We have cloned an EcoR1-HindIII digest fragment (1400 bp) of the duplex cDNA derived from the bovine lung converting enzyme poly(A) + mRNA and also Bal31 deletion fragments generated from the 1400 bp clone. Several of the Bal31 clones contain the active site sequence codons of the enzyme and the complete cDNA sequence of one of these (72 bp) has been determined. We found the amino acid sequence at the active site to be -Phe-Thr-Glu-Leu-Ala-Asn-Ser-, containing the catalytic Glu residue. This sequence is identical with the sequence that we previously determined by manual Edman degradation analysis of the appropriate active-site peptide except that we now find Asn instead of Asp. We have sequenced 670 bp of the 1400 bp clone but have not yet overlapped the active-site sequence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887538 TI - Hb D Los Angeles [beta 121 Glu----Gln] in Japan. PMID- 2887539 TI - Milk-borne transmission of HTLV-I from carrier mothers to their children. AB - In order to clarify the natural transmission route of human T-cell leukemia virus type I (HTLV-I) from mother to child, we have followed two groups of children with ages of 1 to 3 years who were nourished either with HTLV-I-infected breast milk, or with non-infected milk from sero-positive, HTLV-I carrier mothers. Tests for the presence of antibody against HTLV-I revealed that 4 of 6 children in the former group developed HTLV-I infection, while only 1 of 14 children in the latter group became infected. The difference in HTLV-I infection rate for the children in the two groups was statistically significant (P less than 0.01 by chi square). Furthermore, 2 of 4 elder siblings in the former group developed HTLV-I infection, whereas only one of 8 elder siblings in the latter group became infected. The overall rate of HTLV-I infection of breast-fed children born to HTLV-I-carrier mothers was 25% (8/32) by 3 years of age. Five of 6 mothers with HTLV-I-infected cells in the milk also possessed infected cells in their peripheral blood. Conversely 5 of 6 mothers without infected cells in the peripheral blood possessed no infected cells in their breast milk, suggesting that HTLV-I-infected cells in the peripheral blood can enter the breast milk. None of the 8 breast-fed children born to carrier mothers whose peripheral blood and breast milk-borne cells were negative, developed HTLV-I infection, suggesting that HTLV-I transmission from mother to child is dependent upon the number of HTLV-I-infected cells in carrier mothers. PMID- 2887537 TI - The hypothalamus in Parkinson disease. AB - It is currently believed that Parkinson disease (PD) is due to a degenerative process that independently damages multiple areas of the central and peripheral nervous system. Loss of nigrostriatal dopamine is now widely recognized as being directly related to the motor symptoms in Parkinson's disease. Parkinsonian patients also exhibit symptoms and signs suggestive of hypothalamic dysfunction (e.g. dysautonomia, impaired heat tolerance). The latter clinical features are supported by pathological, biochemical and endocrinological findings. Lewy body formation has been demonstrated in every nucleus of the hypothalamus, specifically the tuberomamillary and posterior hypothalamic. Preferential involvement of the hypothalamus was also noted in patients after post encephalitic parkinsonism. Loss of dopamine (30-40%) in the hypothalamus of affected patients has been shown in recent studies, and is compatible with the reported abnormalities of growth hormone release in response to L-dopa administration, elevated plasma levels of MSH, and reduced CSF levels of somatostatin and beta-endorphins in these patients. Deranged immunological mechanisms have been found in PD patients including the presence of autoantibodies against sympathetic ganglia neurons, adrenal medulla and caudate nucleus. On the evidence of on pathological studies demonstrating the early vulnerability of the hypothalamus in aging and PD, and the known role of the hypothalamus in immune modulation, we expect that it will be shown that primary damage of the hypothalamus leads to subsequent secondary degeneration of structures receiving direct projections from the hypothalamus. Within this framework, the dopaminergic systems may be damaged, since striatal dopamine synthesis and receptor sensitivity have been shown to be regulated by ACTH and alpha-MSH through direct arcuate nucleus-striatal projections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887540 TI - Proficiency testing of water microbiology laboratories in The Netherlands. AB - In a 3-year period, four series of simulated water samples containing selected test strains were distributed to more than 50 laboratories in The Netherlands for bacteriological testing. Participating laboratories examined the samples by enrichment or membrane filtration methods, or both, for total coliform organisms, thermotolerant coliform organisms, faecal streptococci and standard plate counts (37 degrees and 22 degrees C) according to Dutch standard methods. The results were quantitatively satisfactory: the distribution of positive and negative results with subsamples conformed to stochastic variation; the standard deviation of membrane or plate counts was usually in the range which may be expected from a Poisson distribution, and there was good correspondence between average counts in participating laboratories and those expected from controls in the organizing laboratory. Problems of a qualitative nature were frequently encountered, however. Among them were a false positive response with a strain of Enterobacter cloacae in the thermotolerant coliform test; a false positive result with Clostridium perfringens in enrichment tests for total or thermotolerant coliform organisms and false positive results with Micrococcus varians in the faecal streptococcus test by membrane filtration. It is concluded that quality assessment should be a consistent activity in water microbiology laboratories. For this purpose, stable and well characterized reference materials are needed. PMID- 2887541 TI - Almitrine bismesylate and the central and peripheral ventilatory response to CO2. AB - Effects of almitrine bismesylate on the peripheral and central chemoreflex to a CO2 challenge during normoxia were studied in nine alpha-chloralose-urethan anesthetized cats. With the dynamic end-tidal CO2 forcing technique the ventilatory response after a square-wave change in end-tidal PCO2 (PETCO2) was partitioned into a central and a peripheral part using a two-compartment model. With almitrine administered intravenously (0.6 mg/kg followed by a maintenance dose of 0.4 mg.kg-1 X h-1) the CO2 sensitivity of the peripheral chemoreflex increased on the average from 0.315 to 0.564 l.min-1 X kPa-1 (P less than 0.001, 6 cats, 73 runs), whereas the CO2 sensitivity of the central chemoreflex remained the same (P = 0.87). The extrapolated PETCO2 at zero ventilation (apneic threshold) of the (total) steady-state response curve decreased on the average from 3.50 to 2.36 kPa (P less than 0.001). With the artificial brain stem perfusion technique it was confirmed that almitrine did not affect ventilation by administering it to the blood perfusing the brain stem. We conclude that almitrine bismesylate during normoxia enhances the CO2 sensitivity of the peripheral chemoreflex loop and decreases the apneic threshold due to an action located outside the brain stem. PMID- 2887542 TI - Perceived exertion and gas exchange after calcium and beta-blockade in atrial fibrillation. AB - Nine male patients (mean age 65 yr) with chronic atrial fibrillation underwent maximal exercise testing during placebo, beta-adrenergic (celiprolol, 600 mg), or calcium (diltiazem, 30 or 60 mg four times daily) channel blockade. The results were analyzed to determine which factors most closely related to ratings of perceived exertion (RPE) during exercise. Heart rate (HR), blood pressure (BP), oxygen uptake (VO2), minute ventilation (VE), and carbon dioxide production (VCO2) were evaluated at rest, 3.0 mph/0% grade, the gas exchange anaerobic threshold (ATge), 80% of placebo maximal O2 uptake, and maximal exercise. Both beta-adrenergic and calcium channel blockade significantly reduced heart rate and systolic blood pressure relative to placebo; these effects were more profound during beta-adrenergic blockade and as exercise progressed. Correlation coefficients and estimates of slope were derived for changes in RPE during exercise vs. changes in HR, VO2, VE, and VCO2 during the three treatments (r = 0.76 to 0.92, P less than 0.001). Although RPE was significantly correlated with HR during placebo and diltiazem therapy (r = 0.45, P less than 0.01), this was not the case during beta-adrenergic blockade (r = 0.31, NS). Slope of the regression lines between RPE and VO2, VE, and VCO2 did not differ between the three treatments. Slope of the regression lines between RPE and HR differed only during calcium channel blockade. Because the presence of atrial fibrillation and beta-adrenergic blockade altered the associations between RPE, VO2, and HR, these results suggest that VE is more closely related to RPE than the other parameters. PMID- 2887543 TI - Isolation, genetic mapping, and characterization of Escherichia coli K-12 mutants lacking gamma-glutamyltranspeptidase. AB - Escherichia coli K-12 mutants lacking gamma-glutamyltranspeptidase (EC 2.3.2.2) were isolated after mutagenesis of cells with ethyl methanesulfonate. They lost the enzyme activity to different extents. The mutations of two mutants that had lost the enzyme activity completely were mapped at 76 min of the E. coli K-12 linkage map. These mutations made the cells neither nutrient requiring nor cold sensitive. The mutants leaked much more glutathione into the medium than the wild type. We propose the symbol ggt for these mutations. PMID- 2887544 TI - Western blot (immunoblot) analysis of the fimbrial antigens of Bacteroides nodosus. AB - The roles of the fimbrial subunit and the putative basal protein antigens in the serological classification of Bacteroides nodosus have been examined by Western blot (immunoblot)-antibody binding studies of fimbriae isolated from a wide range of strains representative of different serogroups and serotypes. Fimbrial subunits were recognized by antiserum against the homologous serogroup but not generally by heterologous antisera, whereas recognition of the basal antigen was independent of serological classification. Secondary cross-reaction patterns among fimbrial subunits indicated that some serogroups may be more closely related than others. Examples include serogroups C and G and serogroups D and H. Similar analyses of isolates classified within serotypes A1 and A2, with serotype specific antisera, showed that this subdivision is also determined by the fimbrial subunit and that significant variation does occur even at this level. These studies suggest that the various serogroups and serotypes of B. nodosus comprise a series of overlapping sets of antigenically related strains. PMID- 2887545 TI - Assimilation of 13NH4+ by Azospirillum brasilense grown under nitrogen limitation and excess. AB - The specific activities of glutamine synthetase (GS) and glutamate synthase (GOGAT) were 4.2- and 2.2-fold higher, respectively, in cells of Azospirillum brasilense grown with N2 than with 43 mM NH4+ as the source of nitrogen. Conversely, the specific activity of glutamate dehydrogenase (GDH) was 2.7-fold higher in 43 mM NH4+-grown cells than in N2-grown cells. These results indicate that NH4+ could be assimilated and that glutamate could be formed by either the GS-GOGAT or GDH pathway or both, depending on the cellular concentration of NH4+. The routes of in vivo synthesis of glutamate were identified by using 13N as a metabolic tracer. The products of assimilation of 13NH4+ were, in order of decreasing radioactivity, glutamine, glutamate, and alanine. The formation of [13N]glutamine and [13N]glutamate by NH4+-grown cells was inhibited in the additional presence of methionine sulfoximine (an inhibitor of GS) and diazooxonorleucine (an inhibitor of GOGAT). Incorporation of 13N into glutamine, glutamate, and alanine decreased in parallel in the presence of carrier NH4+. These results imply that the GS-GOGAT pathway is the primary route of NH4+ assimilation by A. brasilense grown with excess or limiting nitrogen and that GDH has, at best, a minor role in the synthesis of glutamate. PMID- 2887546 TI - Fimbria-associated proteins of Bacteroides loescheii PK1295 mediate intergeneric coaggregations. AB - Bacteroides loescheii PK1295 serves as a coaggregation bridge between Streptococcus sanguis 34 and Actinomyces israelii PK14, two gram-positive oral bacteria that are otherwise unable to coaggregate. Whereas coaggregation with S. sanguis 34 is inhibited by lactose, no simple sugar was found that inhibited coaggregation with A. israelii PK14. Coaggregation-defective (Cog-) mutants of B. loescheii PK1295 were isolated for the purpose of identifying the surface components responsible for the interaction with each coaggregation partner. Selection for spontaneously occurring Cog- mutants gave rise to two phenotypic classes of mutants. Type I lost the ability to coaggregate with S. sanguis 34, whereas type II failed to coaggregate with either S. sanguis 34 or A. israelii PK14. Purified fimbriae from the parent agglutinated cells of both partners, and agglutination with S. sanguis 34 was inhibited by lactose. Denaturing polyacrylamide gel electrophoresis and immunoblot analysis demonstrated the presence of both a 75- and a 43-kilodalton (kDa) protein associated with parental fimbriae, but only a 43-kDa protein was seen with fimbriae prepared from the type I mutant. Neither polypeptide was found in similar preparations from the type II mutants. Our data suggest that coaggregation of B. loescheii PK1295 with both gram-positive partners is mediated by fimbria-associated proteins present on the surface of the gram-negative organism and that the 75- and 43-kDa polypeptides are responsible for the recognition of S. sanguis 34 and A. israelii PK14 cells, respectively. PMID- 2887547 TI - Structure of Bordetella pertussis peptidoglycan. AB - Bordetella pertussis Tohama phases I and III were grown to the late-exponential phase in liquid medium containing [3H]diaminopimelic acid and treated by a hot (96 degrees C) sodium dodecyl sulfate extraction procedure. Washed sodium dodecyl sulfate-insoluble residue from phases I and III consisted of complexes containing protein (ca. 40%) and peptidoglycan (60%). Subsequent treatment with proteinase K yielded purified peptidoglycan which contained N-acetylglucosamine, N acetylmuramic acid, alanine, glutamic acid, and diaminopimelic acid in molar ratios of 1:1:2:1:1 and less than 2% protein. Radiochemical analyses indicated that 3H added in diaminopimelic acid was present in peptidoglycan-protein complexes and purified peptidoglycan as diaminopimelic acid exclusively and that pertussis peptidoglycan was not O acetylated, consistent with it being degraded completely by hen egg white lysozyme. Muramidase-derived disaccharide peptide monomers and peptide-cross-linked dimers and higher oligomers were isolated by molecular-sieve chromatography; from the distribution of these peptidoglycan fragments, the extent of peptide cross-linking of both phase I and III peptidoglycan was calculated to be ca. 48%. Unambiguous determination of the structure of muramidase-derived peptidoglycan fragments by fast atom bombardment mass spectrometry and tandem mass spectrometry indicated that the pertussis peptidoglycan monomer fraction was surprisingly homogeneous, consisting of greater than 95% N-acetylglucosaminyl-N-acetylmuramyl-alanyl-glutamyl diaminopimelyl++ +-alanine. PMID- 2887549 TI - P.R.N. medications in child state hospital inpatients. AB - The authors reviewed the administration of p.r.n. medications over 12 months in 49 child psychiatry inpatients. There were 1263 p.r.n. administrations (mean +/- SD = 25.6 +/- 36.7 administrations/patient). Only 7 (14%) of the 49 patients had none; 9 (18%) had more than 50. The number of p.r.n. administrations correlated with the dose of regular neuroleptics and with the time spent in seclusion. Age, race, sex, diagnosis, neurological disorders, IQ, and self-injurious behavior were poor predictors of the number of p.r.n. administrations. Antihistaminics accounted for 54% (683) of the p.r.n. administrations, neuroleptics for 24% (303), and chloral hydrate for 17% (214). Seventy percent (891) of the p.r.n. drugs were given for disruptive behavior. Only 32% (403) of the 1263 administrations were clearly effective, 14% (170) were ineffective, and 54% (690) were dubious. A controlled trial is needed to assess the efficacy of this ubiquitous psychiatric practice. PMID- 2887548 TI - Mutations that create new promoters suppress the sigma 54 dependence of glnA transcription in Escherichia coli. AB - Escherichia coli rpoN mutants lack sigma 54 and are therefore unable to initiate the transcription of glnA at glnAp2, which is required for the production of a high intracellular concentration of glutamine synthetase. We have found that the dependence on sigma 54 can be overcome by mutations that have apparently created a new sigma 70-dependent promoter. The position -35 RNA polymerase contact site of this new promoter overlaps glnAp2. The initiation of transcription at the new promoter is inhibited by sigma 54-RNA polymerase even in the absence of nitrogen regulator I-phosphate, the activator required for the initiation of transcription at glnAp2. The results suggest that in cells growing with an excess of nitrogen and therefore lacking nitrogen regulator I-phosphate, sigma 54-RNA polymerase is bound at glnAp2. PMID- 2887550 TI - Comparison of severe and mild tardive dyskinesia: implications for etiology. AB - Nineteen patients with severe tardive dyskinesia were compared with 45 patients with mild tardive dyskinesia on demographic and treatment variables. Age, sex, duration and number of psychiatric hospitalizations, and amount and duration of neuroleptic treatment did not discriminate between mild and severe tardive dyskinesia. Severe tardive dyskinesia patients were treated with significantly (p less than .01) fewer neuroleptics and had significantly (p less than .05) shorter neuroleptic-free periods. Onset was more rapid in severe tardive dyskinesia patients than in mild tardive dyskinesia patients. Severe tardive dyskinesia is more likely t result from greater patient vulnerability than from heavier neuroleptic exposure. Unipolar depressed patients who are older and on higher neuroleptic dosages may be more susceptible to severe tardive dyskinesia. PMID- 2887551 TI - Metoprolol in the treatment of neuroleptic-induced tremor: case report. AB - A case report is presented documenting definite beneficial effect of metoprolol, a beta-selective adrenoceptor antagonist, in alleviating neuroleptic-induced coarse tremors. The tremors could not be controlled with antiparkinsonian agents. Metoprolol may prove to be an effective alternative in managing such side effects as tremors. The possible mechanisms of action are discussed. PMID- 2887552 TI - Behavioral toxicity of antipsychotic drugs. AB - Extrapyramidal symptoms cause much misery, often go undiagnosed, and can interfere with treatment and rehabilitation. Akinesia is a behavioral state of diminished motoric and psychic spontaneity that is difficult to distinguish from the negative symptoms of schizophrenia. The most useful clinical correlates of akinesia are a subjective sense of sedation and excessive sleeping. Akinesia interferes with social adjustment and may manifest as "postpsychotic depression." The subjective restlessness of akathisia is usually accompanied by telltale foot movements: rocking from foot to foot while standing or walking on the spot. Akathisia is strongly associated with depression and dysphoric responses to neuroleptics and has even been linked to suicidal and homicidal behavior in extreme cases. PMID- 2887553 TI - A double-blind crossover comparison of antiparkinson drug therapy: amantadine versus anticholinergics in 90 normal volunteers, with an emphasis on differential effects on memory function. AB - Anticholinergic antiparkinson drugs administered orally at standard clinically prescribed doses impaired new memory acquisition and mood in normal volunteer subjects, based on tests of free recall, recognition memory, and time production, self-rating of memory function, and an evaluation of mood states. Elderly subjects were more severely impaired than were young adults. Amantadine did not impair new memory acquisition, and on self-report measures, it was significantly better tolerated than were anticholinergics. Among patients being treated for psychotic illness, there are two groups in which an effort to avoid anticholinergic therapy is especially worthwhile because of the severe consequences of memory dysfunction. These individuals are young neuroleptic responsive patients who are in an early stage of their disease and elderly patients. For these two groups, amantadine should be considered as the initial mode of treatment, with low-dose anticholinergics being used for those patients who do not achieve adequate relief from extrapyramidal side effects with amantadine. PMID- 2887554 TI - Treating extrapyramidal reactions: some current issues. AB - "Extrapyramidal" reactions to antipsychotic drugs include acute dystonias, akathisia, Parkinson's syndrome, and tardive dyskinesia. Recent research suggests efficacy of prophylactic antiparkinson drugs in diminishing the incidence of acute dystonia in high-risk patients, although the use of lower neuroleptic doses also might lower the risk and cause fewer unwanted effects. New in the treatment of akathisia is the use of beta-blockers, specifically propranolol (Inderal and others). Many patients require maintenance antiparkinson drug therapy during prolonged antipsychotic drug treatment. There is no effective treatment for tardive dyskinesia, the prevalence of which may be growing, with an estimated annual incidence of new cases of 3%-4%; the elderly and patients with affective illness may be at greatest risk. Clinicians are also attending to the related syndrome of tardive dystonia. PMID- 2887555 TI - Extrapyramidal side effects: a historical perspective. AB - A historical review of the adverse reactions to neuroleptic agents- extrapyramidal side effects--is presented. Soon after its introduction in 1952, chlorpromazine was noted to induce symptoms resembling Parkinson's disease. At first, these symptoms were thought to be related to the drug's antipsychotic effect. Later, more careful research showed that they are not directly associated with the antipsychotic activity of neuroleptic agents. More recently, extrapyramidal side effects have gained importance because they are significant factors in both the patient's acceptance of the particular drug and his or her social adjustment. PMID- 2887556 TI - On the mechanism of the reconstitution of F1-depleted ATPase complex with purified F1: possible conformational effects. AB - The membrane sector (F0) of H+-ATPase was prepared by trypsin and urea treatment of F1-F0 and reconstituted with purified F1. The oligomycin sensitivity of the reconstituted F1-F0 complex obtained by treating F1 or F0 with Mg2+ before binding is much higher than that obtained without Mg2+ treatment. The greater change in the intrinsic fluorescence of the reconstituted F1-F0 complex obtained by Mg2+ treatment suggests that conformational changes may occur during the reconstitution. We deduce that Mg2+ binds to membrane lipids, thus decreasing membrane fluidity and changing the physical state of the lipids to provide a suitable microenvironment for conformational changes in F0. The data also suggest that the conformational change in the F0 portion of the F1-F0 complex can be transmitted to the F1 portion, the conformation of which is in turn altered, resulting in the formation of an F1-F0 complex with high oligomycin sensitivity. On the other hand, Mg2+ may act on F1 directly to induce a suitable conformational change which is then transmitted to F0, resulting in the formation of an H+-ATPase with greater sensitivity to oligomycin. PMID- 2887557 TI - The mechanism of lead-induced mitochondrial Ca2+ efflux. AB - Addition of Pb2+ to rat kidney mitochondria is followed by induction of several reactions: inhibition of Ca2+ uptake, collapse of the transmembrane potential, oxidation of pyridine nucleotides, and a fast release of accumulated Ca2+. When the incubation media are supplemented with ruthenium red, the effect of Pb2+ on NAD(P)H oxidation, membrane delta psi, and Ca2+ release are not prevented if malate-glutamate are the oxidizing substrates; however, the latter two lead induced reactions are prevented by ruthenium red if succinate is the electron donor. It is proposed that in mitochondria oxidizing NAD-dependent substrates, Pb2+ induces Ca2+ release by promoting NAD(P)H oxidation and a parallel drop in delta psi due to its binding to thiol groups, located in the cytosol side of the inner membrane. In addition, it is proposed that with succinate as substrate, the Ca2+ -releasing effect of lead is due to the collapse of the transmembrane potential as a consequence of the uptake of Pb2+ through the calcium uniporter, since such effect is ruthenium red sensitive. PMID- 2887558 TI - A human hepatoma cell line expresses a single-chain form of gamma-glutamyl transpeptidase. AB - Mammalian gamma-glutamyl transpeptidases characterized thus far have been shown to be heterodimeric glycoproteins. The two subunits are derived from a single chain propeptide which, in the rat kidney, exhibits low transpeptidase activity (less than 2% of the dimeric enzyme). A human hepatoma-derived cell line, Hep G2, expresses relatively high transpeptidase activity. The enzyme is primarily localized on the cell surface and exhibits catalytic properties similar to the dimeric human kidney and lymphoid cell transpeptidase. Significantly, the Hep G2 enzyme, unlike the enzyme from other human tissues, is a single-chain species, Mr = 120,000. PMID- 2887559 TI - Topographical separation of the catalytic sites of asparagine synthetase explored with monoclonal antibodies. AB - Monoclonal antibodies which inhibited the enzymatic activity of bovine pancreatic asparagine synthetase were mapped to two topographically separate regions of the enzyme surface using competitive binding assays. Three antibodies which all inhibited glutamine- and NH3-dependent synthesis of asparagine bound to a common antigenic region. A fourth monoclonal antibody which interfered with glutamine binding or cleavage but not with NH3-dependent synthesis of asparagine was mapped to a separate region of the enzyme surface. These findings suggest a topographical separation between the aspartyl-AMP and glutamine-binding sites of bovine pancreatic asparagine synthetase. Three noninhibitory antibodies exhibited conformation-dependent binding and were mapped to a third region of the enzyme. Binding assays were used to demonstrate extensive cross-reaction of these antibodies with asparagine synthetases isolated from bovine liver and sheep pancreas. Substantial cross-reactions were also seen with the enzyme isolated from rat liver or pancreas, a human tumor cell line, and a mouse tumor cell line. Of the four antibodies that inhibited glutamine- and NH3-dependent synthesis of asparagine from ruminant species, only one bound to and inhibited the enzyme from rat liver or mouse cells, which suggests significant structural differences between the ruminant and rodent enzymes. PMID- 2887561 TI - Two types of transglutaminase in the PC12 pheochromocytoma cell line. Stimulation by sodium butyrate. AB - Transglutaminases are a class of enzymes capable of covalently cross-linking both intracellular and extracellular proteins. The activity of tissue transglutaminase is known to decrease precipitously following neoplastic transformation, and it has been hypothesized that transglutaminase may be involved in growth regulation. We have found that the differentiation promoter sodium butyrate is able to cause a marked increase in transglutaminase activity in PC12 pheochromocytoma cells in a time- and dose-dependent manner. This increased transglutaminase activity is associated with growth arrest, as well as with striking morphological changes including increased cell adhesion. The transglutaminase induced by sodium butyrate appears to be tissue transglutaminase, based on its cytosolic localization, thermal lability at basic pH, and elution profile on anion-exchange chromatography. Untreated PC12 cells contain only small amounts of transglutaminase which resembles epidermal transglutaminase, an enzyme previously described only in skin. In contrast to sodium butyrate, nerve growth factor did not stimulate tissue transglutaminase in PC12 cells, although it, too, caused growth arrest. It is hypothesized that transglutaminase may be involved in certain morphological changes accompanying cellular differentiation and neoplastic transformation, rather than in growth regulation per se. PMID- 2887560 TI - Evidence for functional heterogeneity among the catalytic sites of the bovine heart mitochondrial F1-ATPase. AB - The characteristics of ATP hydrolysis at a single catalytic site of the bovine heart F1-ATPase (MF1) as originally described by Grubmeyer et al. (Grubmeyer, C., Cross, R.L., and Penefsky, H.S. (1982) J. Biol. Chem. 257, 12092-12100) were compared with those of various chemically modified preparations of MF1 in which the steady state activity was severely attenuated. Although it was not necessary to age our preparations of native MF1 in the presence of 2 mM Pi to observe the same characteristics of single site catalysis, such aging did shift the equilibrium of bound substrate and bound products at the single catalytic site in favor of ATP. After loading a single catalytic site on the enzyme with substoichiometric [alpha,gamma-32P]ATP, the addition of 5-20 microM ATP or ADP was effective in promoting both the hydrolysis of bound [alpha,gamma-32P]ATP and release of radioactive products. Under these conditions, the 5-20 microM ATP added as promoter was hydrolyzed at a rate commensurate with the turnover rate of the enzyme, whereas the promoted hydrolysis of the [alpha,gamma-32P]ATP, preloaded at a single catalytic site, was considerably slower. Therefore, the high affinity, single catalytic site loaded first does not directly contribute to steady state ATP hydrolysis. That the single, high affinity catalytic site is not a "normal" catalytic site is supported by the properties of enzyme modified by 5' p-fluorosulfonylbenzoyladenosine which exhibits only slightly altered characteristics of single site catalysis and promoted single site catalysis, despite exhibiting severely attenuated steady state turnover. Other modified forms of the enzyme in which the steady state activity was severely attenuated by derivatization with 5'-p-fluorosulfonylbenzoylinosine, 7-chloro-4 nitrobenzofurazan, or 1,5-difluoro-2,4-dinitrobenzene also bound substoichiometric ATP at a single catalytic site. However, the characteristics of single site hydrolysis by these modified forms of the enzyme differed considerably from those of native MF1. PMID- 2887562 TI - Generation of nitro radical anions of some 5-nitrofurans, 2- and 5 nitroimidazoles by norepinephrine, dopamine, and serotonin. A possible mechanism for neurotoxicity caused by nitroheterocyclic drugs. AB - Catecholamine neurotransmitters such as norepinephrine, dopamine, and related catecholamine derivatives reduce nitroheterocyclic drugs such as nitrofurantoin, nifurtimox, nifuroxime, nitrofurazone, misonidazole, and metronidazole in slightly alkaline solutions. Drugs which contain 5-nitrofurans are reduced at lower pH than drugs which contain 2- and 5-nitroimidazoles. 5-Nitroimidazole derivatives such as metronidazole and ronidazole are known to be more difficult to reduce than 2-nitroimidazole derivatives, due to their lower redox potential. Catecholamines, when reducing nitro drugs, undergo concomitant oxidation to form semiquinone radicals. Both semiquinone radicals and nitro anion radicals formed in a reaction of nitro drug and catecholamine derivative were detected by electron spin resonance spectroscopy. Oxygen consumption studies in solutions containing nitro drug and catecholamine derivative showed that nitro anion radicals formed under aerobic conditions reduce oxygen to form the superoxide radical and hydrogen peroxide. Quinones formed in the reaction of catecholamine and nitro drug were detected by optical spectroscopy. Biosynthetic precursors and some metabolic products of catecholamines were also used in these studies, and they all exhibited reactions similar to catecholamines. Bovine chromaffin granules which synthesize and store catecholamines produced the nitrofurantoin anion radical when intact granules were treated with nitrofurantoin. These radicals formed inside the granules were observed by ESR spectroscopy. The formation of nitrofurantoin radical, semiquinone radicals of catecholamines, and oxygen-derived radicals by chromaffin granules is proposed to cause damage to adrenal medulla, and this process may lead to neurotoxicity. PMID- 2887563 TI - Activation of alpha 1-adrenoceptors, protein kinase C, or treatment with intracellular free Ca2+ elevating agents increases pineal phospholipase A2 activity. Evidence that protein kinase C may participate in Ca2+-dependent alpha 1-adrenergic stimulation of pineal phospholipase A2 activity. AB - The regulation of pineal phospholipase A2 activity was studied indirectly by measuring the release of [3H]arachidonic acid from [3H]arachidonic acid-labeled tissue in organ culture and the formation of radiolabeled lysophosphatidylcholine by glands labeled with 32Pi or [14C]choline. Glands were transferred sequentially through a series of 10-min incubations in label-free medium. Norepinephrine (10( 5) M) stimulated [3H]arachidonic acid release by 2-fold; release peaked during the first 10 min and returned to basal levels during the third incubation period. Studies with selective alpha 1-, alpha 2-, and beta-adrenergic agents indicated that norepinephrine was acting through alpha 1-adrenergic receptors. Ca2+ appears to play a critical role because the effects of norepinephrine were mimicked by treatment with the Ca2+ ionophore A23187 and inhibited by inorganic Ca2+ channel blockers or EGTA; other [Ca2+]i elevating treatments also stimulated [3H]arachidonic acid release. The possibility that protein kinase C may be involved was studied because it is activated by the alpha 1-adrenergic agonist phenylephrine in the pineal gland (Sugden, D., Vanecek, J., Klein, D. C., Thomas, T. P., and Anderson, W. B. (1985) Nature 314, 359-361). Three protein kinase C activators stimulated [3H]arachidonic acid release with the same relative potency as that established for activation of protein kinase C (4 beta-phorbol 12 myristate 13-acetate greater than 4 beta-phorbol 12,13-dibutyrate greater than 1 oleoyl 2-acetylglycerol). The effects of norepinephrine, A23187, and protein kinase C activators appear to be mediated by phospholipase A2 because the effects of these compounds on [3H]arachidonic acid release are blocked by an established inhibitor of this enzyme, mepacrine, and because these compounds stimulate the formation of 32P- and 14C-labeled lysophosphatidylcholine by glands incubated with 32Pi or [14C]choline. In addition, an inhibitor of diacylglycerol lipase, another enzyme which generates arachidonic acid, did not inhibit the stimulation of [3H]arachidonic acid release by norepinephrine, A23187, or a phorbol ester. Cyclic nucleotides do not appear to play an important role in the regulation of phospholipase A2 activity because dibutyryl cyclic AMP does not alter [3H]arachidonic acid release and also because the amounts of cAMP and cGMP in the culture medium are not consistently associated with [3H]arachidonic acid release. These findings suggest that pineal phospholipase A2 activity is controlled by norepinephrine acting via an alpha 1-adrenergic mechanism which might involve Ca2+ and protein kinase C. PMID- 2887564 TI - Covalent cross-linking of prostaglandin E receptor from bovine adrenal medulla with a pertussis toxin-insensitive guanine nucleotide-binding protein. AB - Prostaglandin E2 (PGE2) specifically bound to 100,000 X g pellet prepared from bovine adrenal medulla, and [3H]PGE2-bound proteins were solubilized with 3-[(3 cholamidopropyl)dimethylammonio]-1-propanesulfonic acid. The dissociation of bound [3H]PGE2 from the proteins was enhanced by GTP. [3H]PGE2-specifically bound proteins were adsorbed onto a wheat germ agglutinin column and GTP treatment decreased the amount of [3H]PGE2 retained on the column. When [3H]PGE2-bound proteins were cross-linked in the membrane by dithiobis(succinimidyl propionate) and solubilized, bound [3H]PGE2 was no longer dissociated by GTP treatment, suggesting that cross-linking produced a stable and high-affinity complex of PGE receptor with a GTP-binding protein. Covalent cross-linking of the complex was attested by adsorption of dithiobis(succinimidyl propionate)-treated [3H]PGE2 bound proteins to GTP-Sepharose, and co-elution of [35S]guanosine 5'-O-(3 thiotriphosphate) binding activity and immunoreactivities of alpha o and beta subunits of a GTP-binding protein. The cross-linked [3H]PGE2-bound complex was eluted as an apparently single radioactive peak at the position of Mr = 200,000 by gel filtration. These results have demonstrated that PGE receptor is a glycoprotein with an approximate Mr of 110,000, assuming that the Mr of the GTP binding protein is 90,000. PGE2 neither activated nor inhibited adenylate cyclase activity, and pertussis toxin (islet-activating protein) did not affect PGE2 binding and its GTP sensitivity. These results suggest that the PGE receptor may be functionally associated with a pertussis toxin-insensitive GTP-binding protein and is not coupled to the adenylate cyclase system in bovine adrenal medulla. PMID- 2887565 TI - Two distinct forms of receptors for atrial natriuretic factor in bovine adrenocortical cells. Purification, ligand binding, and peptide mapping. AB - The atrial natriuretic factor (ANF) receptor of bovine adrenal cortex was solubilized with Triton X-100 and purified by sequential chromatography on ANF (99-126)-agarose, GTP-agarose, and wheat germ agglutinin-Sepharose. Two subtypes of ANF receptors were isolated, both of which showed specific ANF binding, whereas one of the ANF receptor subtypes also possessed significant cyclase activity. Both of the receptors showed high capacities (Bmax = 5.7-6.8 nmol/mg of protein) and high affinities (Kd = 54-68 pM) for ANF-(99-126). The cyclase-free receptor had high affinity (Ki = 150-220 pM) to C-terminal truncated ANF analogs, whereas the cyclase-containing receptor had a much weaker affinity (Ki = 10(6) 10(7) pM). When treated with dithiothreitol, the purified cyclase-containing and cyclase-free ANF receptors migrated as a single band at Mr 135,000 and 62,000, respectively, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified cyclase-free receptor is not a product derived from the cyclase containing receptor because (i) two proteins with Mr of 135,000 and 62,000 were specifically labeled with 4-azidobenzoyl 125I-ANF-(102-126) in nonsolubilized intact membranes; (ii) the truncated ANF analogs (10(4) pM) prevented the photolabeling of the 62,000-dalton protein but not that of the 135,000-dalton protein; and (iii) two-dimensional peptide mapping showed more than 90% difference between the profiles of the two purified ANF receptor subtypes. This study provides first direct evidence for the existence of two distinct ANF receptors which are different not only in their pharmacological properties but also in their primary structure. PMID- 2887566 TI - Purification and characterization of two distinct complexes of assembly polypeptides from calf brain coated vesicles that differ in their polypeptide composition and kinase activities. AB - The binding and assembly of clathrin triskelions on vesicle membranes seem to be mediated by certain assembly polypeptides (Keen, J.H., Willingham, M.C., and Pastau, I.H. (1979) Cell 16, 303-312). These assembly polypeptides were further purified into two distinct complexes using hydroxylapatite chromatography. Peak 1 consists of two major bands of 98 and 112 kDa, two minor bands of 103 and 118 kDa, and a polypeptide of 46 kDa. Peak 2 consists of one major band of 100 kDa, two minor bands of 103 and 115 kDa, and a polypeptide of 50 kDa. Both complexes have a native molecular mass of 290 kDa as determined by gel filtration. Each 290 kDa complex contains two polypeptides of 98-118/100-115 kDa and two polypeptides of 46/50 kDa. The 46-kDa polypeptide is not phosphorylated, whereas the 50-kDa polypeptide is. Both peaks contain 50-kDa kinase-like activity. Time courses of the 50-kDa phosphorylation show that the activity in peak 1 saturates much faster than the activity in peak 2; there may be two 50-kDa kinase activities in coated vesicles. A kinase that phosphorylates the polypeptides in 98-118-kDa group is present in peak 1 but not in peak 2. Both peaks assemble clathrin triskelions into cages under conditions in which the clathrin alone would not assemble. Both rotary shadowed and negatively stained preparations of these reassembled cages as well as the purified complexes were examined by electron microscopy. Thus, two complexes have been identified that differ in their polypeptide composition and kinase activities, but are similar in their ability to assemble clathrin triskelions into cages. PMID- 2887567 TI - Highly frequent single amino acid substitution in mammalian elongation factor 2 (EF-2) results in expression of resistance to EF-2-ADP-ribosylating toxins. AB - Toxin-resistant polypeptide chain elongation factor 2 cDNA has been cloned from a mutant hamster cell line with only non-ADP-ribosylatable elongation factor 2. The mutation conferring resistance to diphtheria toxin and Pseudomonas aeruginosa exotoxin A is a G-to-A transition in the first nucleotide of codon 717. Codon 715 encodes a histidine residue that is modified post-translationally to diphthamide, which is the target amino acid for ADP-ribosylation by both toxins. Transfection of mouse L cells with a recombinant elongation factor 2 cDNA differing from the wild-type only by this G-to-A transition confers resistance to P. aeruginosa exotoxin A. The degrees of toxin-resistant protein synthesis of stable transfectants are dependent on the ratio of non-ADP-ribosylated elongation factor 2 to wild-type elongation factor 2, not the amount of non-ADP-ribosylated elongation factor 2. The mutation creates a new Mbo II restriction site in the elongation factor 2 gene. Several independently isolated diphtheria toxin resistant Chinese hamster ovary cell lines show the same alteration in the Mbo II restriction pattern. PMID- 2887568 TI - Identification of the primary translation product of atrial natriuretic peptide receptor mRNA in a cell-free system using anti-receptor antiserum. AB - The primary translation product of mRNA encoding atrial natriuretic peptide (ANP) receptor has been shown to have an Mr of 58,000. Poly(A)+ RNA was isolated from the bovine kidney and lung and translated in a rabbit reticulocyte lysate system containing [35S]methionine. Immunoprecipitation of the labeled translation products, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography, identified a 58-kDa protein as the primary translation product which is the unglycosylated precursor to be processed to the glycosylated mature 70-kDa form found in the plasma membranes. The result lends strong support to our previous proposal that mature ANP receptor is composed of two disulfide-linked 70 kDa subunits, eliminating the possibility that the two 70-kDa subunits arise from a larger 140-kDa precursor by proteolytic cleavage. PMID- 2887569 TI - Product inhibition of carboxypeptidase H. AB - Carboxypeptidase H is one of several enzymes required for the processing of peptide hormone precursors. In this study, inhibition of carboxypeptidase H by its peptide products was investigated. Carboxypeptidase H activity in bovine adrenal medulla chromaffin granules and rat adrenal medulla homogenate was inhibited by the peptides Met- and Leu-enkephalin, vasopressin, oxytocin, luteinizing hormone-releasing hormone, substance P, and thyrotropin-releasing hormone, with oxytocin and ACTH 1-14 having the least effect, at concentrations of 2-20 mM. Inhibition by amidated peptide products (vasopressin, oxytocin, luteinizing hormone-releasing hormone, substance P, and thyrotropin-releasing hormone) show that the final products of the precursor processing pathway can regulate carboxypeptidase H. These levels of peptides are similar to known intragranular peptide concentrations indicating that product and feedback inhibition of carboxypeptidase H may play a role in the control of neuropeptide synthesis. The proenkephalin-derived peptides Met-enkephalin, Leu-enkephalin, Met enkephalin-Arg6-Gly7-Leu8, and Met-enkephalin-Arg6-Phe7 competitively inhibited bovine and rat carboxypeptidase H with Ki values of 12.0, 6.5, 7.0, and 5.5 mM, respectively. The significantly greater Ki for Met-enkephalin may reflect the effects of higher intragranular concentration of Met-enkephalin, since one proenkephalin molecule contains four copies of Met-enkephalin and only one copy of each of the other enkephalin peptides. Thus, the products from one multivalent precursor molecule may equivalently inhibit carboxypeptidase H activity. Product inhibition of carboxypeptidase H and perhaps other processing enzymes may serve to limit the maximum peptide concentration within the secretory vesicle. PMID- 2887570 TI - Isolation of the glutamyl peptide labeled by the nucleotide analogue 2-(4-bromo 2,3-dioxobutylthio)-1,N(6)-ethenoadenosine 2',5'-biphosphate in the active site of NADP+-specific isocitrate dehydrogenase. AB - 2-(4-Bromo-2,3-dioxobutylthio)-1,N(6)-ethenoadenosine 2',5'-bisphosphate (2-BDB-T epsilon A-2',5'-DP) is an affinity label for the coenzyme-binding site of pig heart NADP+-dependent isocitrate dehydrogenase. Specific reaction occurs at the coenzyme site with an incorporation of 0.5 mol of reagent/mol of enzyme subunit (i.e. modification of only one subunit of the dimeric enzyme) (Bailey, J.M., and Colman, R.F. (1985) Biochemistry 24, 5367-5377). Modified enzyme, prepared by incubating 1 mg/ml isocitrate dehydrogenase with 75 microM 2-BDB-T epsilon A 2',5'-DP in the absence and presence of substrate or coenzyme, was reduced with NaBH4, carboxymethylated, and digested with trypsin. Nucleotidyl peptides were isolated by chromatography on DEAE-cellulose, followed by treatment with acid phosphatase (to decrease the negative charge by removing the phosphate groups from covalently bound reagent) and rechromatography on the same DEAE-cellulose column. The isolated peptides were characterized by amino acid analysis, dansylation, and gas-phase sequencing. A single triskaidekapeptide corresponding to modification of the coenzyme site by 2-BDB-T epsilon A-2',5'-DP was identified as: Asp-Leu-Ala-Gly-X-Ile-His-Gly-Leu-Ser-Asn-Val-Lys. Additional evidence indicated that X is a glutamate residue derivatized by 2-BDB-T epsilon A-2',5' DP. PMID- 2887572 TI - Post-translational processing of preprosomatostatin-II examined using fast atom bombardment mass spectrometry. AB - The products and an intermediate of preprosomatostatin-II processing in the anglerfish islet were purified and subjected to structural analysis. The peptides isolated identify the site of signal cleavage (between Ser-24 and Gln-25). The prohormone is further processed at Arg-97 and, to a lesser extent, at the two adjacent basic amino acid residues Lys-61 and Arg-62. A 28-residue somatostatin is also generated which can be hydroxylated at Lys-23. A proteolytic processing site which would form the 14-residue somatostatin does not appear to be used to a significant degree. Fast atom bombardment mass spectrometry (FABMS) was used to demonstrate that the amino-terminal residues of peptides 25-60, and 25-90 are pyroglutamic acid, a modification which precludes Edman degradation of these peptides. Analysis of the peptides and tryptic peptide maps by FABMS allowed confirmation of the sites of prohormone conversion and indicated that terminal basic residues were removed during processing. Three amino acid residues were also found to differ from the amino acid sequence deduced from the cDNA and were localized to specific regions by FABMS analysis. Residues found to differ from the cDNA (cDNA in parentheses) were: Asp-77 (Thr), Val-78 (Phe), and Gly-90 (Glu). Mass assignments were confirmed by running a single cycle of Edman degradation prior to FABMS. The peptides noted above were also examined by Edman sequence analysis. The sequence of a cDNA clone to preprosomatostatin-II was re examined in light of the observed differences at the protein level. This study emphasizes the utility of FABMS in prohormone processing studies and in identification of post-translational processing events. PMID- 2887571 TI - Purification and properties of prostaglandin E1/prostacyclin receptor of human blood platelets. AB - Activation of platelet adenylate cyclase by prostaglandin E1 or prostacyclin is initiated through the interaction of the agonists with the same receptors on membrane. Prostaglandin E1/prostacyclin receptors of human platelets were solubilized in buffer, containing 0.05% Triton X-100 and protease inhibitors. The soluble membrane protein was chromatographed on a DEAE-cellulose column and assayed by a microfiber filter by equilibrium binding technique. The active fractions eluted at 0.7 M KCl were pooled, and the receptors were purified to homogeneity by Sephadex G-200 gel filtration with an overall recovery of 30%. The isolated receptor was 2,200-fold purified over the starting platelets. As evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the receptor showed a molecular mass of 190,000 daltons and is composed of two nonidentical subunits with molecular masses of 85,000 and 95,000 daltons. The interaction of prostaglandin E1 with the purified receptor was rapid, saturable, reversible, and highly specific. Among all prostaglandins tested, only prostacyclin was capable of displacing [3H]prostaglandin E1 bound to the receptor. Scatchard analysis of [3H]prostaglandin E1 binding to the purified receptor suggested the presence of a single class of high affinity binding sites (Kd = 9.8 nM) and a second population of low affinity binding sites (Kd = 0.7 microM) in the same protein molecule. Incubation of the purified receptor with platelets stripped of the receptor by washing with low concentrations of Triton X 100 efficiently restored the ability of prostaglandin E1 and prostacyclin to activate adenylate cyclase in these cells. PMID- 2887573 TI - Modified nuclear processing of alpha 1-acid glycoprotein RNA during inflammation. AB - Rat alpha 1-acid glycoprotein is an acute phase reactant which shows a marked elevation in mRNA level following inflammatory induction. It has been proposed that both transcriptional and post-transcriptional mechanisms regulate the induction of the gene. We have studied the processing of the primary transcript of alpha 1-acid glycoprotein. The preferred pathway of intron removal was determined by Northern blot analysis and was found to be unaltered after inflammatory stimulation. The final nuclear precursor did exhibit size alterations, manifest as a quantitative shift from the final precursor at 6 h to a second progressively shorter form at 18 and 24 h. Deadenylation of nuclear RNA showed that the difference in size of the precursor is due to a change in poly(A) tail length, which occurs after the splicing out of the last intron. Nuclear run on transcription assays measured a 2.5-fold increase in transcriptional activity, with a peak at 12 h. The highest level of cytoplasmic RNA with a long poly(A) tail, however, occurs before 12 h. Our data suggest that the reduction in poly(A) tail size is due to a rapid trimming of the tail in the nucleus and that this process is modified upon inflammatory induction. PMID- 2887574 TI - The gene for ornithine decarboxylase is co-amplified in hydroxyurea-resistant hamster cells. AB - We have constructed a cDNA library from the highly hydroxyurea-resistant hamster cell line 600H in which the activity of ribonucleotide reductase is elevated more than 80-fold. Using the technique of differential hybridization, we have isolated a number of cDNA clones from this library which are homologous to genomic DNA sequences amplified in the 600H cell line compared to the V79 parental line. One of these cDNA clones by sequence analysis was found to code for ornithine decarboxylase. This was confirmed by in vitro translation of poly(A+) RNA isolated by hybridization-selection followed by immunoprecipitation with antiserum specific for mouse ornithine decarboxylase. Genomic sequences homologous to the cDNA clone were shown to be sequentially amplified 6-20-fold in hamster cell lines selected stepwise for resistance to increasing concentrations of hydroxyurea. Genomic sequences homologous to a cDNA for the M2 subunit of ribonucleotide reductase were also amplified in these cell lines, and the degree of M2 sequence amplification corresponded to the degree of amplification of ornithine decarboxylase sequences, suggesting that the two genes had been co amplified during the selection of the hydroxyurea-resistant phenotype. PMID- 2887577 TI - Distribution and modulation of the cellular receptor for transforming growth factor-beta. AB - Scatchard analyses of the binding of transforming growth factor-beta (TGF-beta) to a wide variety of different cell types in culture revealed the universal presence of high affinity (Kd = 1-60 pM) receptors for TGF-beta on every cell type assayed, indicating a wide potential target range for TGF-beta action. There was a strong (r = +0.85) inverse relationship between the receptor affinity and the number of receptors expressed per cell, such that at low TGF-beta concentrations, essentially all cells bound a similar number of TGF-beta molecules per cell. The binding of TGF-beta to various cell types was not altered by many agents that affect the cellular response to TGF-beta, suggesting that modulation of TGF-beta binding to its receptor may not be a primary control mechanism in TGF-beta action. Similarly, in vitro transformation resulted in only relatively small changes in the cellular binding of TGF-beta, and for those cell types that exhibited ligand-induced down-regulation of the receptor, down regulation was not extensive. Thus the strong conservation of binding observed between cell types is also seen within a given cell type under a variety of conditions, and receptor expression appears to be essentially constitutive. Finally, the biologically inactive form of TGF-beta, which constitutes greater than 98% of autocrine TGF-beta secreted by all of the twelve different cell types assayed, was shown to be unable to bind to the receptor without prior activation in vitro. It is proposed that this may prevent premature interaction of autocrine ligand and receptor in the Golgi apparatus. PMID- 2887579 TI - Application of column switching in high-performance liquid chromatographic analysis of medroxalol in plasma. AB - An automated high-performance liquid chromatographic (HPLC) column-switching system is described for the analysis of medroxalol, a potential antihypertensive agent, in plasma. The HPLC system uses two six-port switching valves with a Corasil C18 short pre-column for an on-line sample clean-up and an SGE ODS analytical column for separation. Plasma samples were diluted with a phosphate buffer (pH 7.2) containing an internal standard and aliquots were injected directly on the HPLC system. The column-switching system was applicable to continuous analysis of hundreds of plasma samples since this technique provided very efficient on-line sample clean-up and regenerated the pre-column effectively. Results were in good agreement and the total analysis time was one third that of an alternative method. PMID- 2887578 TI - Continuity of care in asthma management. PMID- 2887576 TI - Three-dimensional reconstruction of a peroxisomal reticulum in regenerating rat liver: evidence of interconnections between heterogeneous segments. AB - The three-dimensional (3-D) form and the interrelationship of peroxisomes (Po) in the model of regenerating rat liver after partial hepatectomy were studied by computer-assisted 3-D reconstruction of serial ultrathin sections. Po were labeled cytochemically for either catalase, which stains them all uniformly, or for D-amino acid oxidase (DAA-OX), which gives a heterogeneous reaction with lightly and darkly stained PO. In regenerating rat liver, Po exhibit marked pleomorphism with some budding forms and dumbbell-shaped ones. The 3-D reconstruction revealed many single spherical Po measuring 0.15-0.8 micron in diameter. In addition, two to five Po were found interconnected with each other via narrow 30-50-nm hourglass-shaped bridges forming a reticulum. Such aggregates of Po measured 1.5-2.5 microns across. Whereas all segments of this reticulum stained homogeneously for catalase, they exhibited a marked difference in the intensity of the DAA-OX reaction. These observations are consistent with the view of peroxisomal proliferation by budding or fragmentation from preexisting ones. Under such conditions of rapid growth as in regenerating liver, Po may be interconnected forming a reticulum. The interconnections between Po with differing DAA-OX activities suggest that they originate from the same parent organelle. PMID- 2887575 TI - Acidification of the cytosol inhibits endocytosis from coated pits. AB - Acidification of the cytosol of a number of different cell lines strongly reduced the endocytic uptake of transferrin and epidermal growth factor. The number of transferrin binding sites at the cell surface was increased in acidified cells. Electron microscopic studies showed that the number of coated pits at the cell surface was not reduced in cells with acidified cytosol. Experiments with transferrin-horseradish peroxidase conjugates and a monoclonal anti-transferrin receptor antibody demonstrated that transferrin receptors were present in approximately 75% of the coated pits both in control cells and in cells with acidified cytosol. The data therefore indicate that the reason for the reduced endocytic uptake of transferrin at internal pH less than 6.5 is an inhibition of the pinching off of coated vesicles. In contrast, acidification of the cytosol had only little effect on the uptake of ricin and the fluid phase marker lucifer yellow. Ricin endocytosed by cells with acidified cytosol exhibited full toxic effect on the cells. Although the pathway of this uptake in acidified cells remains uncertain, some coated pits may still be involved. However, the data are also consistent with the possibility that an alternative endocytic pathway involving smooth (uncoated) pits exists. PMID- 2887580 TI - Sensitive high-performance liquid chromatographic method for procaterol in human urine. PMID- 2887581 TI - Column liquid chromatographic measurement of betaxolol in plasma or serum. PMID- 2887582 TI - Determination of xamoterol in human plasma by high-performance liquid chromatography with electrochemical detection. PMID- 2887583 TI - 25-Hydroxyvitamin D3 metabolism by human T-lymphotropic virus-transformed lymphocytes. AB - Production of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] by human T-lymphotropic virus-I (HTLV-I)-infected lymphocytes may be the cause of the hypercalcemia frequently found in HTLV-I-associated adult T-cell lymphoma/leukemia. We examined three HTLV-I-transformed lymphocyte cell lines, two HTLV-II-transformed lymphocyte cell lines, and six HTLV-negative B and T-lymphocyte leukemia cell lines for metabolism of 25-hydroxyvitamin D3 (25OHD3). One HTLV-I-positive cell line, designated S-LB1, converted the substrate 25OH-[3H]D3 to several more polar metabolites, which were identified by high performance liquid chromatographic analysis as putative 1,25-(OH)2D3, 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3], and 1,24,25-trihydroxyvitamin D3 [1,24,25-(OH)3D3]. The other cell lines gave no evidence of 25OH-[3H]D3 metabolism. Likewise, phytohemagglutinin-stimulated normal human lymphocytes did not metabolize 25OH-[3H]D3. The characteristics of 25OHD3 metabolism by S-LB1 cells were investigated in more detail. Kinetic studies revealed average Km values of 92 and 383 nM for 25OHD3 1-hydroxylase and 24-hydroxylase, respectively. Time-course studies showed that both 1,25-(OH)2 [3H]D3 and 24,25-(OH)2-[3H]D3 were further metabolized by S-LB1 cells to more polar compounds [primarily 1,24,25-(OH)3D3] and to compounds from which part of the side-chain had been cleaved. Exogenous 1,25-(OH)2D3 (1) inhibited endogenous 1,25-(OH)2D3 production, (2) stimulated 24,25-(OH)2D3 production, and (3) stimulated production of compounds more polar than 1,25-(OH)2D3. Bovine PTH-(1 34) had no effect on 25OH-[3H]D3 metabolism by S-LB1 cells. Our results indicate that the 25OH-[3H]D3-metabolizing system of cultured HTLV-I-transformed S-LB1 lymphocytes is similar but not identical to that of kidney cell culture systems. It appears, however, that infection of lymphocytes with HTLV does not uniformly result in acquisition of the competence to metabolize 25OHD3. PMID- 2887584 TI - Bilateral abscessed orchiepididymitis associated with sepsis caused by Veillonella parvula and Clostridium perfringens: case report and review of the literature. AB - Veillonella species is a gram-negative coccus which is part of the anaerobic normal flora in the oral cavity, small intestine, upper respiratory tract, vagina, and urinary tract. The role that this organism plays in infection is not well known, and it is generally associated with other bacteria. We present a case of bilateral abscessed orchiepididymitis associated with septicemia due to Veillonella parvula and, later, to Clostridium perfringens, with the development of severe renal insufficiency and septic shock, which resolved favorably with antibiotic therapy, treatment of shock, and hyperbaric oxygen therapy. In reviewing the literature, we have not found any other case of sepsis due to Veillonella sp. associated with urological disorders. PMID- 2887585 TI - Blastocystis hominis and human disease. PMID- 2887586 TI - Differential protooncogene expression characterizes histopathologically indistinguishable tumors of the peripheral nervous system. AB - We have found highly predictable patterns of protooncogene expression in cell lines and tumor tissue of neuroblastoma (NB), a tumor of the peripheral nervous system (PNS). These patterns make it possible to recognize two different genetically definable subgroups among histopathologically indistinguishable tumors. Additionally, we have identified a difference in neurotransmitter biosynthetic enzyme activity in these two subgroups of NB. The patterns of protooncogene expression and neurotransmitter biosynthetic enzymes suggests that these tumors arise in different cells of the PNS. PMID- 2887588 TI - The value of self-report assessment in studies of anxiety disorders. AB - This review compares the sensitivities of a physician-rated scale, the Hamilton Anxiety Scale (HAS), and a patient-rated scale, the Hopkins Symptom Checklist (HSCL), in detecting the anti-anxiety effects of benzodiazepines in a large sample of placebo-controlled trials. Scales and subscales were compared within the same study, a methodologic feature unique to this review. The total score, psychic factor, and somatic factor of the HAS were equally sensitive to the effects of benzodiazepines. The total score, anxiety factor, and somatization factor of the HSCL also were equally sensitive. The HAS total score, however, was consistently more sensitive than any of the HSCL scores. There was no evidence that physicians used side effects to make their ratings more sensitive. Sedative side effects, however, adversely affected the sensitivity of patient ratings. The data suggest that patient ratings reflect a cost-benefit computation taking account of both antianxiety and sedative effects. PMID- 2887589 TI - Pharmacological management of manic psychosis in an unlocked setting. AB - There has been a resurgence in the past few years of exploring alternative pharmacological agents in the management of manic psychosis. An open clinical trial was conducted on an unlocked ward investigating the use of benzodiazepines as adjunctive therapy with lithium or carbamazepine, with some of the patients also receiving neuroleptics. Twelve patients meeting DSM-III criteria for bipolar affective disorder, manic type, were treated. Patient response was monitored with use of the Brief Psychiatric Rating Scale and the Biegel Mania Rating Scale. The patients all had moderately severe illness upon initiation of the trial. Results indicate that those patients who received benzodiazepines alone were among the better responders, and that when used in combination with neuroleptics, the dose of each drug was quite small. Minimal side effects were noted with this regimen. Our preliminary results suggest that benzodiazepines may be useful as adjunctive treatment in the management of patients with bipolar affective disorder, manic type. PMID- 2887587 TI - Interleukin 1 gene expression in adult T cell leukemia. AB - The adult T cell leukemia (ATL) is a T cell neoplasm etiologically associated with human T lymphotropic virus type I (HTLV-I) infection. ATL cells often abnormally express interleukin 2 (IL-2) receptors, and ATL patients may show clinical evidence of hypercalcemia, osteolytic bone lesions, or increased bone turnover. Whereas interleukin 1 (IL-1) is not generally recognized as a product of T cells, this cytokine is capable of both altering IL-2 receptor expression and activating osteoclasts. Thus, we investigated the possibility that primary ATL leukemic T cells and HTLV-I-infected long-term ATL cell lines produce IL-1. S1 nuclease protection assays demonstrated that primary leukemic ATL cells from five out of six patients, as well as one patient with T4+ chronic lymphocytic leukemia, contained considerable quantities of IL-1 beta messenger RNA (mRNA) and small amounts of IL-1 alpha mRNA. These primary leukemic T cells also released biologically active IL-1 protein as evaluated in the murine thymocyte comitogenesis bioassay. In contrast to primary tumor cells, four out of six long term ATL cell lines produced variable amounts of IL-1 alpha mRNA in the absence of detectable IL-1 beta mRNA as measured by S1 nuclease protection. These data demonstrate that IL-1 gene (especially IL-1 beta) expression occurs in many primary HTLV-I-infected leukemic T cells raising the possibility that this mediator may play a role in the pathological changes associated with this leukemia. Also, these studies show that the pattern of IL-1 alpha and IL-1 beta gene expression differs between primary ATL tumor cells and long-term cultured ATL cell lines, indicating an interesting biological difference in these two HTLV I-infected cell populations. PMID- 2887591 TI - Delirium following benzodiazepine withdrawal. PMID- 2887590 TI - Atenolol and propranolol in neuroleptic-induced akathisia. PMID- 2887592 TI - Localization of immunoreactive tyrosine hydroxylase in the goldfish brain. AB - This report describes the distribution of tyrosine hydroxylase immunoreactive (TH ir) structures in the brain of the goldfish (Carassius auratus). The localization of TH-ir cell groups revealed by immunocytochemical techniques is largely in accordance with catecholamine distribution previously reported in teleosts by using monoamine fluorescence; however, in the telencephalon and diencephalon, several new cell groups are elucidated. In the telencephalon, TH-ir cell bodies are observed in the olfactory bulb, area ventralis telencephali, and the central zone of the area dorsalis telencephali. TH-ir fibers and terminals are moderately dense throughout the telencephalon except for a sparse innervation of the area dorsalis, pars medialis. Immunostained cells are present in the suprachiasmatic nucleus and magnocellular and parvicellular components of the preoptic nucleus. Immunoreactive fibers from preoptic cells can be traced caudally in two main tracts to the infundibulum. Dense immunoreactivity around cells in the pituitary provides anatomical support for catecholamine involvement in the neuroendocrine axis probably via preopticohypophysial connections. At middiencephalic levels, immunoreactive cells are present in the ventral thalamus, nucleus pretectalis periventricularis, pars ventralis, and paraventricular organ pars anterioris. In the caudal diencephalon, TH-ir cells are seen within the posterior tuberal nuclei and dorsal to posterior recess. No immunostained cells are observed in the midbrain. In the hindbrain, tyrosine hydroxylase containing cells comprise three groups similar to that described using Falck-Hillarp histofluorescence (Parent et al., '78), i.e., isthmal, central medullary, and medullospinal groups. Tyrosine hydroxylase immunoreactivity is interpreted as evidence for the presence of catecholamines and not only provides an anatomical basis for the functional significance of catecholamines in teleosts, but may be useful in elucidating homologous structures in tetrapod vertebrates, although certain sites of immunoreactivity may prove to be unique to teleosts. PMID- 2887593 TI - Distribution of acetylcholine and catecholamine neurons in the cat brainstem: a choline acetyltransferase and tyrosine hydroxylase immunohistochemical study. AB - The distribution of acetylcholine neurons in the brainstem of the cat was studied by choline acetyltransferase (ChAT) immunohistochemistry and compared to that of catecholamine neurons examined in the same or adjacent sections by tyrosine hydroxylase (TH) immunohistochemistry. The largest group of ChAT-positive (+) neurons was located in the lateral pontomesencephalic tegmentum within the pedunculopontine tegmental nucleus and the laterodorsal tegmental nucleus rostrally and within the parabrachial nuclei and locus coeruleus nucleus more caudally. TH+ neurons were found to be coextensive and intermingled with ChAT+ neurons in the dorsolateral pontomesencephalic tegmentum, where the number of ChAT+ cells (approximately 18,500) exceeded that of the TH+ cells (approximately 12,000). In the caudal pons, scattered ChAT+ neurons were situated in the ventrolateral tegmentum together with TH+ neurons. In the medulla, numerous ChAT+ cells were located in the lateral tegmental field, where they extended in a radial column from the dorsal motor nucleus of the vagus to the ventrolateral tegmentum around the facial and ambiguus nuclei, occupying the position of preganglionic parasympathetic neurons of the 7th, 9th, and 10th cranial nerves. TH+ cells were also present in this field. Neurons within the general visceral, special visceral, and somatic motor cranial nerve nuclei were all immunoreactive to ChAT. Scattered ChAT+ neurons were also present within the medullary gigantocellular and magnocellular tegmental fields together with a small number of TH+ neurons. Other groups of ChAT+ cells were identified within the periolivary nuclei, parabigeminal nucleus, prepositus hypoglossi nucleus, and the medial and inferior vestibular nuclei. Acetylcholine neurons thus constitute a heterogeneous population of cells in the brainstem, which in addition to including the somatic and visceral efferent systems, comprises many other discrete systems and represents an important component of the brainstem reticular formation. The proximity to and interdigitation with catecholamine neurons within these systems may be of important functional significance. PMID- 2887594 TI - Cholinergic innervation of hippocampal GAD- and somatostatin-immunoreactive commissural neurons. AB - This study describes the cholinergic innervation of chemically defined nonpyramidal neurons in the hilar region of the rat hippocampus. Cholinergic terminals were identified by immunocytochemistry employing a monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine-synthesizing enzyme, and the avidin-biotin-peroxidase (ABC) technique. Nonpyramidal neurons in the hilar region were characterized by immunostaining with antibodies against glutamate decarboxylase (GAD), the gamma aminobutyric acid (GABA)-synthesizing enzyme, and somatostatin (SS). The immunoreactivity to these antibodies was detected by using biotinylated secondary antibodies and avidinated ferritin as an electron-dense marker. This electron microscopic double immunostaining procedure enabled us to demonstrate that immunoperoxidase-labeled ChAT-immunoreactive terminals established symmetric synaptic contacts on the ferritin-labeled GAD- and SS-immunoreactive hilar cells. In additional experiments at least some of the GAD- and SS-immunoreactive hilar neurons were further characterized as commissural neurons by retrograde filling with horseradish peroxidase (HRP) following an injection of the tracer into the contralateral hilus. From these triple labeling experiments, we concluded that at least some GABAergic and somatostatin-containing neurons in the hilar region, which are postsynaptic to cholinergic terminals, project to the contralateral hippocampus. Together with previous studies on the cholinergic innervation of the hippocampus and fascia dentata, our present results thus demonstrate that different types of hippocampal cells, including GABAergic and peptidergic commissural neurons in the hilar region, receive a cholinergic input. PMID- 2887595 TI - Distribution of choline acetyltransferase-, serotonin-, dopamine-beta-hydroxylase , tyrosine hydroxylase-immunoreactive fibers in monkey primary auditory cortex. AB - Immunohistochemical methods were used to visualize choline acetyltransferase (ChAT)-, serotonin-, dopamine-beta-hydroxylase (DBH)-, and tyrosine hydroxylase (TH)-containing fibers in the primary auditory cortex of the cynomolgus monkey (Macaca fascicularis). Each antiserum revealed a subpopulation of axons with a distinct density and laminar distribution. ChAT-immunoreactive fibers were very dense in superficial layers, particularly in layers I, deep III, and IV, and very sparse in layers V and VI. No immunoreactive cell bodies were evident. Serotonin immunoreactive fibers were very dense in all cortical layers but exhibited some subtle laminar differences in fiber size and orientation. The densities of DBH- and TH-immunoreactive fibers were substantially lower than the densities of both ChAT- and serotonin-immunoreactive fibers, particularly in layer IV. However, there were substantial differences between the distribution of TH-immunoreactive fibers and that of DBH-immunoreactive fibers. For example, the density of TH immunoreactive fibers was substantially greater than that of DBH-immunoreactive fibers in layer I. In addition, TH-immunoreactive fibers differed from the other three systems in that TH-immunoreactive fibers exhibited a rostral to caudal gradient of decreasing density. This is the first characterization of the innervation of a specific cortical region by all four of these systems and the first detailed description of the cholinergic innervation of a primate neocortical region utilizing a specific anti-ChAT antiserum. These striking differences in density and laminar distribution suggest that the subcortical extrathalamic systems furnishing these axons differ significantly in their modulation of cortical auditory processing. These data extend observations of previous studies which revealed that the expansion and specialization of the primate neocortex is accompanied by a pronounced regional and laminar differentiation in the intracortical distribution of these highly divergent, extrathalamic afferents. PMID- 2887597 TI - Synaptic structure of the monoamine and peptide nerve terminals in the intermediolateral nucleus of the guinea pig thoracic spinal cord. AB - Synaptic organization of the intermediolateral nucleus of the guinea pig thoracic spinal cord was examined with particular focus on monoamine- and peptide containing nerve terminals. Axon varicosities having flat synaptic vesicles constituted 17% of all axons in the nucleus and formed exclusively symmetric synapses. Enkephalin-, substance P-, somatostatin-, 5-hydroxytryptamine-, and catecholamine-immunoreactive nerve terminals were densely distributed, while neurotensin, vasoactive intestinal polypeptide-, oxytocin-, and cholecystokinin-8 immunoreactive nerves were sparse in the nucleus. Coexistence of 5 hydroxytryptamine and enkephalin was demonstrated, and coexistence of somatostatin and enkephalin as well as somatostatin and 5-hydroxytryptamine in the same axons was also shown by serial semithin sections. Catecholamine axons labelled by 5-hydroxydopamine formed axodendritic and axosomatic synapses and made direct synaptic contacts on the preganglionic sympathetic neurons identified by retrograde transport of horseradish peroxidase. Direct synaptic contacts from enkephalin- and substance P-immunoreactive axons to preganglionic sympathetic neurons were also revealed. Enkephalin-, substance P-, and 5-hydroxytryptamine immunoreactive axons formed axodendritic and axosomatic synapses. Catecholamine axon varicosities constituted 19% of all axon varicosities in the nucleus and 30% of them showed synaptic specializations in a sectional plane. Axon varicosities immunoreactive to enkephalin, 5-hydroxytryptamine, and substance P constituted approximately 35, 19, and 13% of all axon varicosities, respectively, while those with synaptic contacts made up 27, 30, and 26%, respectively, in a sectional plane. Enkephalin-, 5-hydroxytryptamine-, and noradrenaline-immunoreactive axons showed mainly symmetric synaptic contacts. PMID- 2887596 TI - Comparative distribution of mRNAs for glutamic acid decarboxylase, tyrosine hydroxylase, and tachykinins in the basal ganglia: an in situ hybridization study in the rodent brain. AB - Neurotransmitter-related messenger RNAs were detected by in situ hybridization in sections of rat and mouse brains by using 35S-radiolabelled RNA probes transcribed from cDNAs cloned in SP6 promoter-containing vectors. The distribution of messenger RNAs for glutamic acid decarboxylase, tachykinins (substance P and K), and tyrosine hydroxylase was examined in the striatum, pallidum, and substantia nigra. Dense clusters of silver grains were observed with the RNA probe complementary of the cellular messenger RNA for glutamic acid decarboxylase (antisense RNA) over most large neurons in the substantia nigra pars reticulata and medium-sized to large neurons in all pallidal subdivisions. A few very densely and numerous lightly labelled medium-sized neurons were present in the striatum. Among the areas examined, only the striatum contained neurons labelled with the antisense tachykinin RNA. Most of these neurons were of medium size, and a few were large. With the antisense tyrosine hydroxylase RNA, silver grains were found over neurons of the substantia nigra pars compacta and adjacent A10 and A8 dopaminergic cell groups. No signal was observed with RNAs identical to the cellular messenger RNA for glutamic acid decarboxylase or tachykinin (sense RNA). These results show a good correlation with immunohistochemical studies, suggesting that documented differences in the distribution and the level of glutamic acid decarboxylase, tyrosine hydroxylase, and substance P immunoreactivities in neurons of the basal ganglia are related to differences in the level of expression of the corresponding genes rather than to translation accessibility, stability, or transport of the gene products. PMID- 2887598 TI - Self-inflicted tongue ulcer: an unusual form of factitious disorder. AB - Factitious disorders in the buccal cavity are infrequent. A 9-year-old boy with a 5-year history of an artefact ulcer of the tongue is described. Psychiatric evaluation revealed an altered personality structure with a background of psychotic traits. Complete remission was observed with psychiatric management. PMID- 2887599 TI - Is cyclic AMP dependent protein kinase responsible for the in vivo phosphorylation of tyrosine aminotransferase? AB - Undegraded tyrosine aminotransferase was purified to near homogeneity from rat liver and was confirmed to be a substrate for the beef heart cyclic AMP dependent protein kinase catalytic subunit. Specific antibody was used to quantitate the amount of phosphate incorporated into the enzyme. Phosphate incorporation was maximal at a catalytic subunit to tyrosine aminotransferase molar ratio of 7:1 using 200 microM ATP for 30 to 60 min at 30 degrees C. Phospho-peptide maps of tyrosine aminotransferase phosphorylated in vitro by the catalytic subunit were compared with those of amino-transferase immunoprecipitated from 32P labeled cells treated with and without 8-Br cAMP. Whereas the phospho-peptide maps of tyrosine aminotransferase isolated from cells treated with and without 8-Br cAMP were identical, differences were observed in the peptide map of tyrosine aminotransferase phosphorylated in vitro and in vivo. These results were taken to indicate that the catalytic subunit is not responsible for tyrosine aminotransferase phosphorylation in vivo. PMID- 2887600 TI - Autonomic effects on rat submandibular salivary glands. PMID- 2887602 TI - Effect of beta 2-adrenoceptor agonists on saliva proteins and dental caries in asthmatic children. AB - Twenty-four children, from 10 to 20 years old, with asthma treated with beta 2 adrenoceptor agonists were matched with healthy controls of the same age, sex, and social background. Stimulated whole and parotid saliva was collected, and decayed and filled tooth surfaces as well as oral hygiene habits were recorded. The dietary and sugar intake was carefully checked by a four-day dietary record. The asthmatic children had a 26% lower (p less than 0.05) value for secretion rate of whole saliva. Seventy percent of the children with Streptococcus mutans counts greater than 2 X 10(5) colony-forming units/mL of whole saliva belonged to the asthmatic group (p less than 0.05). The concentrations of total protein and amylase in parotid saliva were significantly lower for the asthmatic children. The concentrations of potassium, salivary peroxidase, bacteria-aggregating glycoproteins, and secretory IgA were not affected, but the secretion rate of parotid saliva was 36% lower in the asthma group (p less than 0.05). Oral hygiene and dietary habits did not differ between the groups. The asthmatic children had higher DFS scores, but these were not significantly different from those of the healthy controls (p = 0.07). We suggest that subjects with asthma treated with beta 2-receptor agonists should receive special prophylactic attention. PMID- 2887601 TI - Membrane-associated and solubilized ATPases of Streptococcus mutans and Streptococcus sanguis. AB - The proton-translocating, membrane ATPases of oral streptococci have been implicated in cytoplasmic pH regulation, acidurance, and cariogenicity. Membranes were isolated from Streptococcus mutans GS-5 and Streptococcus sanguis NCTC 10904 following salt-induced lysis of cells treated with lysozyme and mutanolysin. The ATPase activities of these membranes were 1.8 and 1.1 units per mg membrane protein, respectively. F1 ATPases were washed free from the membranes and purified by fast protein liquid chromatography (FPLC). Hydrolytic activities of the F1 ATPases were maximal at pH values between 6.0 and 6.6, whereas the membrane-bound enzymes had pH maxima of 7.5 (S. sanguis) and 6.0 (S. mutans). The F1 ATPases of the streptococci were similar to the well-characterized enzyme of Escherichia coli; they consisted of five different polypeptides and had apparent, aggregate molecular weights of from 335 to 350 Kd. The membrane-bound ATPases were characterized biochemically and found to be similar to those of proton translocating ATPases of E. coli and Streptococcus faecalis. Km values for the membranes with respect to ATP were found to be 0.9 and 1.0 mmol/L for S. mutans and S. sanguis, respectively. Both enzymes had specificities for purine triphosphates and were active with a variety of divalent cations, although optimal activity occurred with ATP and Mg. The membrane-associated enzymes were sensitive to the inhibitors dicyclohexylcarbodiimide (DCCD) and azide, but insensitive to ouabain and vanadate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887604 TI - Management of nausea and vomiting: physiological, pharmacological, and therapeutic considerations. AB - Most incidences of nausea and vomiting can be avoided by careful movement of the patient from a supine position to walking, sound hemostatic principles, and prudent postoperative medication prescribing habits. However, when therapeutic intervention becomes necessary, the clinician should ascertain the probable source of vomiting center activation before selecting a particular pharmacological agent. Although many agents are available, there is little evidence of superior efficacy for agents other than those listed in Table 3. PMID- 2887603 TI - Neurotransmitter control of secretion. AB - It is very well established that the principal control of salivary secretion is derived from autonomic innervation. Transmission of a neural signal to a salivary gland acinar cell occurs chemically via neurotransmitters, the first messengers of a secretory response. Neurotransmitters bind to specific cell surface receptor proteins, an event which activates precise transduction mechanisms which then transfer the neural signal to the inside of the cell. There are two major transduction mechanisms operative in salivary gland acinar cells. One involves the generation of cAMP, the other involves the breakdown of plasma membrane polyphosphoinositides. For both mechanisms, the appropriate stimulated receptor activates a second plasma membrane protein, termed an N (or G) protein. The N protein requires GTP to activate an enzyme (adenylate cyclase or phospholipase C), which then catalyzes the formation of a second messenger (cAMP and inositol trisphosphate/diacylglycerol, respectively). This action provides the intracellular signal for secretory events (protein, fluid, electrolyte secretion) to begin. PMID- 2887605 TI - A report from the Workshop on Pharmacology, Asthma Mortality Task Force. PMID- 2887606 TI - Nutrition education research: reaching toward the leading edge. AB - The work of the past ten years in the field of nutrition education research is reviewed and analyzed. First, definitions of key concepts are provided. Second, the author reviews and assesses the influences from the five nutrition education research conferences held in the past. Presented are results from a survey conducted that asked nutrition educators about the usefulness of the five conferences. Third, results are presented from a review of research articles published since 1980 in JADA, JNE, and HERJ. Implications for designing nutrition education research studies are discussed. Fourth, direction is provided for the future of nutrition education research, with special attention given to the necessary link between researchers and practitioners, so that "right" questions get asked and "correct" answers get used. PMID- 2887607 TI - Studies of the in vitro effect of methylmercury chloride on rat brain neurotransmitter enzymes. AB - The in vitro effect of methylmercury (MM) on the enzymatic activities of brain cell specific marker enzymes, choline acetyltransferase (CAT), glutamic acid decarboxylase (GAD), 2',3'-cyclic nucleotide phosphohydrolase (CNP), glutamine synthetase (GS) and enolase was examined. The results demonstrate that at 100 microM MM, GS activity was not affected whereas a small decrease in the activity of both GAD (20%) and enolase (10%) was observed. CNP and CAT activity appeared to be more sensitive toward MM with 100 microM MM producing inhibition of 50% and 30%, respectively. The addition of sulfhydryl protecting reagents such as DTT or sodium thioglycolate can restore the enzyme activities to normal control levels despite prior exposure of the enzymes to MM. PMID- 2887608 TI - Studies on gamma-glutamyl transpeptidase (GGT) after di(2-ethylhexyl) phthalate (DEHP) exposure. AB - Administration of Di(2-ethylhexyl)phthalate (DEHP) at doses of 250, 500, 1000 and 2000 mg/kg to adult rats was found to significantly increase the activity of gamma-glutamyl transpeptidase (GGT) in liver and serum in a dose-dependent manner. The data indicate that DEHP can be hepatotoxic since an increase in serum GGT levels are indicative of hepatobiliary dysfunction and liver malignancy. An assay of GGT in serum of the individuals exposed to DEHP could be helpful in early detection of liver disorders due to this widely used plasticizer. PMID- 2887610 TI - Decrease in blood pressure by stimulation of the rat hypothalamic paraventricular nucleus with L-glutamate or weak current. AB - Effects of electrical and chemical stimulation of the paraventricular nucleus (PVN) of the hypothalamus on blood pressure were examined in rats anesthetized with urethane-chloralose. Focal electrical stimulation (10-25 microA, 50 Hz, 0.5 ms) of sites within the PVN consistently decreased blood pressure, while the stimulation of regions adjacent to the PVN produced no change or weak depressor response. Microinjection of L-glutamate (0.5 M, 80 nl) to the PVN consistently led to decreased blood pressure, while the same amount of saline injection had no effect. The depressor response was not affected by cervical vagotomy but was markedly reduced after intravenous administration of hexamethonium. The results suggest that activation of PVN neurons in rats leads to a decrease in blood pressure. PMID- 2887609 TI - Study of possible transmitters in the solitary tract nucleus of the cat involved in the carotid sinus baro- and chemoreceptor reflex. AB - By using a multibarrelled microelectrode, the possibility that putative transmitters may influence on the field potential evoked in the solitary tract nucleus by electrical stimulation of the carotid sinus nerve (the NTS response) was examined electrophysiologically in the cat. After iontophoretic application of a selective antagonist to the putative transmitter, it was determined whether or not the NTS response was influenced. Both substance P antagonist and naloxone altered the NTS response recorded in the depressor and apneic (or hypopneic) response zone as well as in the pressor and apneustic (or inspiratory) response zone throughout the rostral, intermediate and commissure regions, suggesting that substance P and opioid peptide may play the role of excitatory transmitters. Under the polarizing cathodal current which may activate inhibitory inputs to the site of the NTS response, bicuculline and prazosin strongly enhanced the NTS response recorded in the pressor and apneustic zone, while naloxone weakly enhanced the NTS response recorded in the depressor and apneic zone. These results suggest that gamma-aminobutyric acid, alpha-adrenergic agonist and opioid peptide may have an inhibitory influence on the NTS response. PMID- 2887611 TI - Risks of neuroleptic drugs in children. AB - We surveyed members of the Child Neurology Society to examine their attitudes about use of neuroleptic drugs in children and their experiences with neuroleptic induced movement disorders. Sixty percent of the membership responded to our questionnaire. Of these responders, over 99% agreed that there were clinical indications for neuroleptics in children, but their criteria varied. Only a minority of the responders routinely incorporated drug holidays in the therapeutic plans of children treated with neuroleptics. The majority had not had clinical experience with patients who developed chronic movement disorders associated with neuroleptic treatment, but 35% (140/410) had encountered patients whose symptoms they considered typical of tardive dyskinesia. However, some of these patients did not meet strict criteria for diagnosis of this movement disorder. The results suggest that neuroleptic-induced movement disorders occur with significant frequency in children and that more detailed prospective studies of the risks and benefits of these drugs in children are warranted. PMID- 2887612 TI - Famotidine: an evolution in H2 antagonist therapy. Proceedings of a symposium. Sao Paulo, Brazil, September 7-12, 1986. PMID- 2887613 TI - Review of an extensive worldwide study of a new H2-receptor antagonist, famotidine, as compared to ranitidine in the treatment of acute duodenal ulcer. AB - The efficacy and safety of famotidine, a new potent H2-receptor antagonist, has been studied in 1,031 patients by 68 investigators in 19 countries in a worldwide dose-ranging multicenter comparative study. Three doses of famotidine (40 mg h.s., 20 mg b.i.d., 40 mg b.i.d.) were compared to ranitidine 150 mg b.i.d. There were no significant differences between the groups in baseline characteristics, including duodenal ulcer size. Efficacy parameters included daytime and nocturnal symptom relief and duodenal ulcer healing, documented by endoscopy, and defined as complete re-epithelialization of the ulcer crater. Significant reductions from baseline for day and night pain, beginning during the first 24 h period, were found in all four treatment groups (p less than 0.01). There was little difference among the four treatment groups with respect to the percentage of patients healed after 4 and 8 weeks of treatment. Healing rates for the three famotidine groups (40 mg h.s., 20 mg b.i.d., 40 mg b.i.d.) were 88, 92 and 92%, respectively, after 8 weeks of treatment as compared to 91% for the ranitidine group. The occurrence and type of adverse clinical experiences reported was similar for each of the four treatment groups. The most common adverse experiences were headache and diarrhea. The results of this study demonstrate that an h.s. dose of famotidine is equivalent to both b.i.d. famotidine and b.i.d. ranitidine in duodenal ulcer healing and pain relief. In view of possible increased patient compliance with a simplified dosage regimen, famotidine 40 mg h.s. is recommended in the acute treatment of duodenal ulcer. PMID- 2887614 TI - Famotidine once-a-day in the therapy of acute, benign gastric ulcer: a worldwide experience. AB - Three hundred thirty-six patients with endoscopically diagnosed benign gastric ulcers, randomly allocated to treatment with 40 mg famotidine at night or placebo, were evaluated in a double-blind multicenter trial conducted in 14 countries worldwide. After 4 weeks, 294 patients qualified for a "per protocol" analysis. Complete ulcer healing was observed in 70 of 149 patients (47%) treated with famotidine 40 mg at night and in 45 of 145 patients (31%) receiving placebo. Cumulative healing rates at 6 weeks were 65 and 46%, and at 8 weeks 80 and 54%, respectively. There were statistically significant differences between the healing rates at each time point (p less than 0.01). The famotidine treatment was significantly more effective at rapidly reducing the incidence of ulcer-related symptoms. Adverse side effects reported were minor and equally distributed between the two groups. The results of this trial show that 40 mg famotidine administered at night is significantly superior to placebo in both accelerating the healing of benign gastric ulcers and in relieving ulcer symptoms. Since 40 mg famotidine administered at night suppresses exclusively nocturnal acid secretion, these findings support the hypothesis that this factor is also of particular importance in the pathogenesis of gastric ulcers. PMID- 2887615 TI - Famotidine: effective treatment of Zollinger-Ellison syndrome. AB - The ability of famotidine to control gastric acid hypersecretion in 32 patients with Zollinger-Ellison syndrome was compared to that of cimetidine or ranitidine. Equipotent doses of each drug were determined in nine patients and famotidine was nine times more potent than ranitidine and 32 times as potent as cimetidine. Famotidine had a 30% longer duration of action than either ranitidine or cimetidine. The 32 patients were treated with famotidine for a mean follow-up of 10.5 months. No hematologic, biochemical, or clinical toxicity occurred. Famotidine appears to be the histamine H2-receptor antagonist of choice in the treatment of Zollinger-Ellison syndrome. PMID- 2887616 TI - Clinical pharmacology of famotidine: a summary. AB - Famotidine is a competitive histamine H2-receptor antagonist. Its main pharmacodynamic effect in humans is inhibition of gastric acid secretion. Dose related suppression of basal and stimulated (meal, pentagastrin) gastric acid output has been shown with oral doses of 5-40 mg. The 40 mg dose is associated with the highest inhibitory effect, the longest duration of action, and the greatest response uniformity. After oral administration, antisecretory activity begins within 1 h, reaches a maximum in 1-3 h, and lasts 10-12 h. In addition to the earlier onset of effect, intravenous famotidine is about twice as potent as oral, a result consistent with a systemic bioavailability of oral famotidine of about 43%. Studies in patients and in healthy volunteers have shown that famotidine does not affect cardiovascular, renal, endocrine, pancreatic exocrine, or gastrointestinal motility functions. Oral famotidine is incompletely absorbed, reaching peak plasma concentrations in 1-3 h. It is eliminated primarily through the kidneys (about 70%), mostly as the parent compound. Its average elimination half-life in healthy subjects is 2.8 h. Half-life is prolonged nonlinearly in patients with decreased renal function. To date, clinically important interactions with other drugs have not been described for famotidine. PMID- 2887617 TI - Selective elimination of non-lpr lymphoid cells in mice undergoing lpr-mediated graft-vs-host disease. AB - The transfer of lpr BM stem cells into lethally irradiated non-lpr recipients (including the congenic MRL/+ differing only at the lpr locus) causes GVHD characterized by a wasting syndrome. In this study we investigated the interaction between the autoimmune (lpr) and normal (A-Thy) B, T, and RBC cell lineages in two types of radiation chimeras: MRL/lpr plus A-Thy----(MRL/lpr X A Thy)F1 and MRL/+ plus A-Thy----(MRL/lpr X A-Thy)F1. Analysis of B cell repopulation by competitive RIA of serum Igh-1 allotype showed that both the MRL and the A-Thy donor cells initially engrafted. However, by 2 to 4 mo post transplantation the normal A-Thy allotype was barely detectable (reduced greater than 2 orders of magnitude), whereas the autoimmune MRL/lpr allotype persisted at normal levels. Similarly, investigation of the donor origin of peripheral blood T cells by two-color flow cytometry showed that by 8 mo post-transplantation normal A-Thy T cells had been eliminated and only MRL/lpr T cells were present in the circulation. In contrast, erythrocytes from both the MRL/lpr and A-Thy donor strains successfully engrafted the F1 recipients and persisted until the termination of the study. Control chimeras transplanted with a mixture of MRL/+ plus A-Thy BM were stably engrafted with both donor strains in both the erythroid and lymphoid populations. Additional experiments in which either B6/lpr or MRL/lpr (and B6/+ or MRL/+ control) BM cells were transferred into (MRL/lpr X B6/+)F1 and (MRL/lpr X B6/lpr)F1 recipients demonstrated that the development of GVHD was not simply due to increased alloreactivity by the lpr donor cells. In these chimeras only the recipients heterozygous (but not homozygous) for the lpr gene developed lpr-GVHD, although both types of recipients had identical genotypes except at the lpr locus. PMID- 2887618 TI - Immunoregulatory T lymphocytes in man. Soluble antigen-specific suppressor inducer T lymphocytes are derived from the CD4+CD45R-p80+ subpopulation. AB - Regulation of the immune response in man is largely dependent on interactions between cells of the cluster designation 4+ (CD4+) helper/inducer sublineage and the CD8+ suppressor/cytotoxic sublineage. When cultured with autologous antigen primed CD4+ lymphocytes, CD8+ cells differentiate into suppressor T cells (Ts) that specifically inhibit the response of fresh autologous CD4+ cells to the priming antigen only. The current study was undertaken to analyze the roles in this suppressor circuit of subpopulations of the CD4+ sublineage distinguished from one another on the basis of their binding (or lack of binding) to monoclonal antibodies against molecules p80 (Leu8) and CD45R (p220/Leu18/2H4). When examined for the proliferative responses to alloantigenic stimuli, each of the four: CD4+p80+, CD4+p80-, CD4+CD45R+, and CD4+CD45R- populations proliferated vigorously, synthesized interleukin 2 (IL-2) and interferon and released soluble IL-2 receptors. However, the responses to soluble antigens such as Candida and diphtheria toxoid were exhibited by CD4+CD45R-, CD4+p80+, and CD4+p80- cells, but not by CD4+CD45R+ cells. When examined for their ability to induced CD8+ Ts in the Candida-driven suppressor-induction culture system, only CD4+p80+ and CD4+CD45R- cells induced strong suppression. Further, when CD4+CD45R- cells were separated into CD4+CD45R-p80+ and CD4+CD45R-p80- subpopulations, despite the ability of both subpopulations to respond to Candida, only CD4+CD45R-p80+ cells induced autologous CD8+ Ts. Activated CD8+ Ts suppressed not only proliferation but also the release of soluble IL-2 receptors by autologous antigen-activated CD4+ cells. Thus, the antigen-specific suppressor-inducer T cells appear to be derived from the CD4+CD45R-p80+ (Leu3+, Leu8+, 2H4-) subpopulation of the CD4+ sublineage. PMID- 2887619 TI - Stimulation of T lymphocyte proliferation by monoclonal antibodies against GD3 ganglioside. AB - Cell-surface gangliosides are presumed to play a role in cell growth and differentiation. With the use of monoclonal antibodies directed against GD3, a disialoganglioside expressed predominantly by cells of neuroectodermal origin, we have found that GD3 is expressed by a subpopulation of cells of the immune system including: 1) fetal thymocytes in subcortical regions and near vessels, 2) lymph node lymphocytes in interfollicular areas and near vessels, and 3) a small subset of T cells in the peripheral blood. Mouse monoclonal antibodies (two IgGs, one IgM, and F(ab')2 fragments) reacting with GD3 were found to stimulate proliferation of T cells derived from peripheral blood. Proliferation of T cells was observed even in cultures depleted of macrophages, suggesting that activation by anti-GD3 was not dependent on the presence of accessory cells. T cell proliferation was maximum between days 5 and 7 of stimulation and was preceded by expression of interleukin 2 receptors. No stimulation was observed with control antibodies of the identical isotype or with monoclonal antibodies recognizing the gangliosides GD2 or GM2. During stimulation by anti-GD3 monoclonal antibodies, there was an expansion of the GD3+ pool of T cells, but depletion of GD3+ T cells prior to stimulation abrogated the response. Proliferation induced by binding to GD3 could be augmented by exogenous interleukin 2 and phytohemagglutinin. Anti CD3 (T3) monoclonal antibodies had little or no effect. These results demonstrate that binding to GD3 on the surface of T cells can elicit signals for T cell proliferation. PMID- 2887620 TI - Relationship between DQ alpha and DQ beta RFLP and cell surface polymorphisms of class II HLA antigens. AB - DQ alpha and beta DNA probes of the human major histocompatibility complex (MHC) were hybridized to restriction enzyme-digested genomic DNA with the aim of establishing a correspondence between the polymorphisms recognized by classical serology and DNA restriction fragment length polymorphisms (RFLP). In DR homozygous human cell lines, three distinct PstI fragments were recognized by the DQ alpha probe and four PstI fragments were recognized by the DQ beta probe. Each fragment was associated with a different group of DR antigens. Three allelic forms of either DX alpha or beta genes were identified, but none showed any strong association with DR or DQ. Family segregation analysis at the DNA level further confirmed the DR linkage of the DQ alleles in estimations of gene frequencies of different alleles of DQ alpha, DQ beta, DX alpha and DX beta. Evidence was presented that the DQ alpha and DQ beta allelic forms described at the DNA level correspond to polymorphic determinants at the cell surface which can be defined serologically or in cellular assays. Our data suggest that the HLA DQ subregion-encoded alloantigens should be defined at the individual alpha and beta chain levels. PMID- 2887621 TI - Expression of P, type-1, and type-1C fimbriae of Escherichia coli in the urine of patients with acute urinary tract infection. AB - In vivo expression, in human urine, of P, type-1, and type-1C fimbriae by Escherichia coli was analyzed by indirect immunofluorescence. Urine samples from 20 patients with acute urinary tract infection, as well as cultures of the corresponding E. coli isolates, were immunostained with three polyclonal antisera to P fimbriae, antiserum to type-1 fimbriae, monoclonal antibody specific for type-1C fimbriae, and fluorochrome-conjugated second antibodies. P fimbriae were found in 17 urine samples and in 18 of the isolated strains. Type-1-fimbriate bacteria were detected in only nine urine samples, although 18 of the isolated strains expressed type-1 fimbriae after growth in vitro. Four strains possessed type-1C fimbriae; only two expressed type-1C fimbriae in urine. The bacterial populations in urine were heterogeneous, and in each positive staining, only a fraction of the bacterial cells were reactive. The results show that E. coli P fimbriae are expressed and are subject to phase variation in vivo during acute urinary tract infection. PMID- 2887622 TI - Endocrine cells in the human colorectal mucosa: immunocytochemical observations on patients with prolapse or internal procidentia of the rectum. AB - We have examined the occurrence and distribution of endocrine cells storing serotonin and the regulatory peptides somatostatin, glicentin, peptide YY in rectal mucosa on 16 patients with prolapse or intussusception of the rectum. There were no significant differences compared with normal rectal mucosa. Our results do not support the assumption that these endocrine cells of the rectum are involved in the pathophysiology of rectal prolapse. PMID- 2887623 TI - Treatment of perennial allergic rhinitis by sodium cromoglycate plus 0.025 per cent xylometazoline (a double-blind study). AB - The object of this double-blind study was to assess the therapeutic effects of a combination of two per cent sodium cromoglycate and 0.025 per cent xylometazoline compared with a matched placebo. Forty patients were included in the two-week study. The treatment was found to be rapidly effective taking only a day to control symptoms in almost 80 per cent of the patients in the group receiving active treatment. No evidence of rebound effects due to the decongestant was observed during the study. PMID- 2887624 TI - 7-Methyl bile acids: 7 beta-methyl-cholic acid inhibits bacterial 7 dehydroxylation of cholic acid and chenodeoxycholic acid in the hamster. AB - The effect of dietary 7 beta-methyl-cholic acid [0.075% in rodent chow (6.4 mg/animal per day)] on cholesterol and bile acid metabolism was studied and compared with that of cholic acid in the hamster. Following oral administration of 7 beta-methyl-cholic acid for 3 weeks, the glycine-conjugated bile acid analog became a major constituent of gallbladder bile. Biliary cholic acid concentration decreased significantly, while that of chenodeoxycholic acid remained unchanged. Serum and liver cholesterol levels were increased by dietary 7 beta-methyl-cholic acid and by cholic acid. Hepatic microsomal HMG-CoA reductase activity was inhibited (30% of the control value) by both bile acids; cholesterol 7 alpha hydroxylase activity was not affected. In chow controls and cholic acid-fed animals, bacterial 7-dehydroxylation of [14C]chenodeoxycholic acid and [14C]cholic acid was nearly complete. In contrast, dietary 7 beta-methyl-cholic acid effectively prevented the 7-dehydroxylation of the two primary bile acids. These results show that dietary 7 beta-methyl-cholic acid is preserved in the enterohepatic circulation and has an effect on serum and liver cholesterol concentrations similar to those produced by the naturally occurring cholic acid. 7 beta-Methyl-cholic acid is an efficient inhibitor of the bacterial 7 dehydroxylation of the primary bile acids in the hamster. PMID- 2887626 TI - Expression and purification of glutamine synthetase cloned from Bacteroides fragilis. AB - A glutamine synthetase (GS) gene, glnA, from Bacteroides fragilis was cloned on a recombinant plasmid pJS139 which enabled Escherichia coli glnA deletion mutants to utilize (NH4)2SO4 as a sole source of nitrogen. DNA homology was not detected between the B. fragilis glnA gene and the E. coli glnA gene. The cloned B fragilis glnA gene was expressed from its own promoter and was subject to nitrogen repression in E. coli, but it was not able to activate histidase activity in an E. coli glnA ntrB ntrC deletion mutant containing the Klebsiella aerogenes hut operon. The GS produced by pJS139 in E. coli was purified; it had an apparent subunit Mr of approximately 75,000, which is larger than that of any other known bacterial GS. There was very slight antigenic cross-reactivity between antibodies to the purified cloned B. fragilis GS and the GS subunit of wild-type E. coli. PMID- 2887625 TI - R-plasmid-mediated chromosome mobilization in Bordetella pertussis. AB - Antibiotic-resistant and auxotrophic mutants of Bordetella pertussis were isolated. These were used as recipients for the uptake from Escherichia coli of broad-host-range R plasmids R68.45, RP1, and RP1 and RP4 carrying transposons Tn501 and Tn7 respectively. B. pertussis transconjugants from these crosses were used as donors to mobilize StrR, NalR, thr+ and gly+ chromosomal markers to B. pertussis or to B. parapertussis recipient strains. The frequency of plasmid transfer varied and depended on the donor and recipient strains used. Differences in chromosome mobilization frequencies of individual markers were observed and appeared to depend on the presence or absence of transposons Tn501 and Tn7 on the plasmid. Linkage was detected between the gly+ and NalR markers. PMID- 2887627 TI - A scanning electron microscope study of the effect of an enterotoxin from Clostridium perfringens 8-6 on mice of different ages. AB - Intestinal damage to mice caused by an enterotoxin from a coatless spore mutant of Clostridium perfringens type A (8-6) was examined by scanning electron microscopy. Two distinct types of damage were observed, both of which could be correlated with animal age. Damage appeared to occur in a specific sequence similar to that found in previous studies in rabbits. We conclude that the type of ileal tissue damage reflects the mode of toxin incorporation from the gut, which is a function of animal age. PMID- 2887628 TI - Bacteriophages F0lac h, SR, SF: phages which adsorb to pili encoded by plasmids of the S-complex. AB - Phage F0lac is an RNA-containing phage which plates only on strains carrying the plasmid EDP208, a pilus derepressed derivative of the unique incompatibility plasmid F0lac. A host range mutant, phage F0lac h, was selected which plated on strains carrying the ungrouped plasmid pPLS::Tn5 and lysed strains carrying another ungrouped plasmid TP224::Tn10 or the Com9 plasmid R71. An RNA-containing phage, SR, was isolated from sewage on bacteria harbouring plasmid pPLS::Tn5. It was antigenically distinct from the above two phages but had the same host range as phage F0lac h. Phages F0lac h and SR adsorbed unevenly to the shafts of the conjugative pili. Another phage, SF, was filamentous and plated or propagated on strains carrying any of the above plasmids as well as on strains harbouring IncD or F-complex plasmids. Plasmids TP224::Tn10 and pPLS::Tn5 were compatible with representative plasmids of all Inc groups also encoding thick flexible pili. The four plasmids EDP208, R71, TP224::Tn10 and pPLS::Tn5 were compatible with one another except for the reaction of TP224::Tn10 in the presence of pPLS::Tn5 which was slightly ambiguous. The host ranges of the bacteriophages, together with the serological relatedness of the thick flexible pili determined by these four compatible plasmids, suggested that they constitute a new complex, here designated S. PMID- 2887629 TI - Complementation of mutations in Escherichia coli and Bordetella pertussis by B. pertussis DNA cloned in a broad-host-range cosmid vector. AB - A gene library of Bordetella pertussis DNA was constructed in Escherichia coli using the broad-host-range cosmid vector pLAFR1. The average insert size was 24.9 kb. From 500 members of the gene library, clones were identified which complemented trpE, glnA and Thr- mutations in E. coli but none which complemented trpD, trpC, trpB, trpA, proA or Leu- mutations. Four clones were identified which complemented trpE in E. coli. Anthranilate synthase activity was detected in a trpE strain only when it harboured a plasmid from one of these clones; activity was repressed when tryptophan was included in the growth medium. Two clones were identified which complemented glnA of E. coli. A recombinant plasmid from one of these clones also restored some of the nitrogen acquisition functions of glnG and glnL in E. coli. Expression of several B. pertussis virulence-associated products (haemolysin, heat-labile toxin, adenylate cyclase, filamentous haemagglutinin, and the cell-envelope polypeptide of Mr 30,000) was not detected in 500 independent clones. However, by transferring the recombinant plasmids to a mutant of B. pertussis deficient in haemolysin and adenylate cyclase, a plasmid was identified which restored both these activities. PMID- 2887630 TI - Biochemical, behavioural, and endocrine effects of CK 204-933, a novel 8 beta ergolene. AB - CK 204-933 displaces [3H]dopamine and [3H]spiperone with high affinity from D-1 and D-2 recognition sites in membranes of calf caudate. Results from functional in vitro tests suggest that it is a partial agonist at D-1 receptors and an antagonist at D-2 receptors. These opposite effects at dopamine receptor subtypes are also expressed in vivo. For instance, in 6-hydroxydopamine lesioned rats, CK 204-933 induces contralateral rotations which are antagonised by SCH 23390 but not by sulpiride. On the other hand, CK 204-933 induces a long lasting increase of dopamine turnover in rat striatum and antagonises apomorphine-induced gnawing behaviour in rats. CK 204-933 increases prolactin serum levels in rats after subcutaneous administration, whereas after oral administration a moderate decrease of prolactin serum levels was seen. The latter effect is probably due to the formation of active metabolites. CK 204-933 exhibits also a high affinity to [3H]prazosin binding sites and antagonises serotonin-mediated stimulation of adenylate cyclase in rat hippocampus. On the other hand, CK 204-933 has no effect of only very weak effects on noradrenaline and serotonin release from rat cerebral cortex slices, which is consistent with its weak effects on noradrenaline- and serotonin-turnover in rat brain. Based on these properties it is suggested that CK 204-933 could be of therapeutic value in brain diseases associated with disturbances of monoaminergic neurotransmission. PMID- 2887631 TI - Lipid requirement for mu opioid receptor binding. AB - We have previously shown that a partially purified mu opioid receptor from bovine brain requires lipids to exhibit full binding activity. In the present report, we have determined the specificity of this lipid requirement. Lipids active in this regard were found always to contain an acidic head group and a fatty acid with two or more double bonds. Free, polyunsaturated fatty acids were also able to confer high binding activity on the partially purified opioid receptor. The possible roles lipids play in opioid binding are discussed in light of these data. PMID- 2887633 TI - Sodium-dependent proline uptake in the rat hippocampal formation: association with ipsilateral-commissural projections of CA3 pyramidal cells. AB - Na+-dependent uptake of L-[3H]proline was measured in a crude synaptosomal preparation from the entire rat hippocampal formation or from isolated hippocampal regions. Among hippocampal regions, Na+-dependent proline uptake was significantly greater in areas CA1 and CA2-CA3-CA4 than in the fascia dentata, whereas there was no marked regional difference in the distribution of Na+ dependent gamma-[14C]aminobutyric acid ([14C]GABA) uptake. A bilateral kainic acid lesion, which destroyed most of the CA3 hippocampal pyramidal cells, reduced Na+-dependent proline uptake by an average of 41% in area CA1 and 52% in area CA2 CA3-CA4, without affecting the Na+-dependent uptake of GABA. In the fascia dentata, neither proline nor GABA uptake was significantly altered. Kinetic studies suggested that hippocampal synaptosomes take up proline by both a high affinity (KT = 6.7 microM) and a low-affinity (KT = 290 microM) Na+-dependent process, whereas L-[14C]glutamate is taken up predominantly by a high-affinity (KT = 6.1 microM) process. A bilateral kainic acid lesion reduced the Vmax of high-affinity proline uptake by an average of 72%, the Vmax of low-affinity proline uptake by 44%, and the Vmax of high affinity glutamate uptake by 43%, without significantly changing the affinity of the transport carriers for substrate. Ipsilateral-commissural projections of CA3 hippocampal pyramidal cells appear to possess nearly as great a capacity for taking up proline as for taking up glutamate, a probable transmitter of these pathways. Therefore proline may play an important role in transmission at synapses made by the CA3-derived Schaffer collateral, commissural, and ipsilateral associational fibers. PMID- 2887632 TI - Dopamine D-1 receptor and cyclic AMP-dependent phosphorylation in Parkinson's disease. AB - D-1 and D-2 receptor densities, evaluated respectively by [3H]SCH 23390 and [3H]spiperone binding, and DARPP-32 (dopamine and adenosine 3':5'-monophosphate regulated phosphoprotein-32K) concentrations, were studied in the brains of control and parkinsonian subjects postmortem. D-2 receptor density was unchanged in the putamen of parkinsonian patients. D-1 receptor density was unchanged in the putamen and substantia nigra pars reticulata (SNR) of parkinsonian patients, but decreased by 28% in the substantia nigra pars compacta (SNC). DARPP-32, which is localized in the same structures as D-1 receptors of which it is thought to represent the intracellular messenger, decreased by 45% in the putamen, 66% in the SNR, and 79% in the SNC. The decrease in D-1 receptors in the SNC may be due to degeneration of pallidonigral GABAergic neurons, but some of the D-1 receptors may be on the nigrostriatal dopaminergic neurons themselves. The dissociation between the alteration of D-1 receptor densities and DARPP-32 concentrations in both the striatum and substantia nigra, which are of the same order in the two structures, may be an index of functional hypoactivity of D-1 neurotransmission. PMID- 2887634 TI - A comparative study and partial characterization of multi-uptake systems for gamma-aminobutyric acid. AB - Previous work by the authors had indicated that synaptosome-enriched preparations from the cerebral cortex of the rat contained a high-, a medium-, and a low affinity uptake system for gamma-aminobutyric acid (GABA). The present study demonstrated that this phenomenon also prevailed in synaptosomes from rat diencephalon, mesencephalon, and cerebellum, although the Vmax values for the high- and medium-affinity systems in the cerebellum were very low relative to those of the other regions. When a different type of preparation containing nerve endings (glomeruli) was obtained from the cerebellum, it possessed a Vmax value for the high-affinity system that was more similar to that for the corresponding system in synaptosomes from the other brain regions. In contrast to the above situation, synaptosomes from rat olfactory bulb lacked the low-affinity uptake system, as did synaptosomes from dog olfactory bulb. The aspartate/glutamate uptake systems, as measured with D-aspartate, provided a regional pattern quite different from those of GABA uptake. Only two uptake systems, a high- and low affinity system, were observed in all regions tested. All three GABA uptake systems were present in cortical synaptosomes from the mouse, hamster, and guinea pig, and all three systems were sodium dependent, energy dependent, temperature sensitive, and totally inhibited by nipecotic acid. PMID- 2887635 TI - Phosphorylation of purified rat striatal tyrosine hydroxylase by Ca2+/calmodulin dependent protein kinase II: effect of an activator protein. AB - The phosphorylation of tyrosine hydroxylase, purified from rat striatum, was investigated using purified Ca2+/calmodulin (CaM)-dependent protein kinase II. This kinase catalyzed the Ca2+-dependent incorporation of up to 0.8 mol 32PO4/mol tyrosine hydroxylase subunit (62 kilodaltons). Reverse-phase high-performance liquid chromatography mapping of tryptic 32P-peptides established that the Ca2+/CaM-dependent protein kinase II phosphorylated a different serine residue than was phosphorylated by the cyclic AMP-dependent protein kinase. Limited proteolysis sequentially reduced the subunit Mr from 62 to 59 kilodaltons and finally to 57 kilodaltons, resulting in loss of the site phosphorylated by the Ca2+/CaM-dependent protein kinase II, but not the site phosphorylated by the cyclic AMP-dependent protein kinase. Phosphorylation by the Ca2+/CaM-dependent protein kinase II had little direct effect on the kinetic properties of tyrosine hydroxylase, but did convert it to a form that could be activated twofold by addition of an activator protein. This heat-labile activator protein increased the Vmax without affecting the Km for the pterin cofactor. This effect was specific in that the activator protein was without effect on nonphosphorylated tyrosine hydroxylase or on tyrosine hydroxylase phosphorylated by the cyclic AMP dependent protein kinase. These results are consistent with the hypothesis that the "Vmax-type" activation of tyrosine hydroxylase observed upon depolarization of neural and adrenal tissues may be mediated by the Ca2+/CaM-dependent protein kinase II. PMID- 2887637 TI - Excitatory amino acid receptor potency and subclass specificity of sulfur containing amino acids. AB - The sulfur-containing amino acids, L- and D-cysteate, L-cysteine, L- and D cysteine sulfinate, L- and D-cysteine-S-sulfate, L-cystine, L- and D homocysteate, L- and D-homocysteine sulfinate, L-homocysteine, L-serine-O sulfate, and taurine were tested in two excitatory amino acid receptor functional assays and in receptor binding assays designed to label specifically the AA1/N methyl-D-aspartate (NMDA), AA2/quisqualate, and AA3/kainate receptor recognition sites, as well as a CaCl2-dependent L-2-amino-4-phosphonobutanoate site, and a putative glutamate uptake site. Agonist efficacies were determined by chick retinal excitotoxicity and stimulated sodium efflux from rat brain slices. D Homocysteine sulfinate, L-homocysteate, and L-serine-O-sulfate had affinities most selective for the NMDA binding site, whereas the binding affinities of D cysteate, D-cysteine sulfinate, D-homocysteate, and L-homocysteine sulfinate were less selective. However, the correlation of agonist activity sensitive to blockade by D-2-amino-7-phosphonoheptanoate or D-2-amino-5-phosphonopentanoate in the functional assays with affinity in the NMDA binding assay (r = 0.87, p less than 0.005 and r = 0.98, p less than 0.005 for excitotoxicity and sodium efflux, respectively) allows characterization of these sulfur-containing amino acids as acting at NMDA subclass receptors. L-Homocysteate, which has been found in the brain, and L-serine-O-sulfate are selective agonists and could serve as endogenous neurotransmitters at the NMDA receptor. PMID- 2887636 TI - Ammonia-induced release of neurotransmitters from rat brain synaptosomes: differences between the effects on amines and amino acids. AB - The effect of NH4Cl on release of amine and amino acid transmitters from rat brain synaptosomes was investigated. Ammonia (0.1-10 mM) stimulated the secretion of dopamine and 5-hydroxytryptamine in a dose-dependent manner, in a process which was additive with the effect of 40 mM K+, almost unaffected by withdrawal of Ca2+, and markedly decreased by increasing [H+] in the medium. The NH4Cl induced dopamine efflux, in contrast to that caused by high [K+]e, was inhibited by benztropine. The release of gamma-aminobutyric acid, aspartate, and glutamate was unaltered by [NH4Cl] less than 5 mM, but somewhat stimulated at higher levels. Transmembrane pH gradient, acid inside, was dissipated by NH4Cl in a concentration-dependent manner and the internal alkalinization correlated with the stimulation of the rate of dopamine efflux. Transmembrane electrical potential was unaffected by [ammonia] less than 5 mM, but a small depolarization was observed at higher levels. It is postulated that ammonia-induced alkalinization of the intrasynaptic storage granules causes extrusion of amines into the cytoplasm and their subsequent leakage into the medium through a reversal of the plasma membrane transporters. A lack of correlation between the release of amino acid neurotransmitters and the dissipation of the delta pH suggests that in rat brain intrasynaptic vesicles, acidic inside, are unlikely to store substantial amounts of gamma-aminobutyric acid, aspartate, or glutamate. PMID- 2887638 TI - Heat stress and neuroleptic drugs. PMID- 2887639 TI - Coated vesicles and pits during enhanced quantal release of acetylcholine at the neuromuscular junction. AB - Frog neuromuscular junctions were stimulated by different methods to secrete quanta of ACh, and the attendant changes in the ultrastructure of the nerve terminal were assessed by morphometric analysis of electron micrographs. Secretion was stimulated by electrical stimulation at 2 Hz or by application of the secretagogues, lanthanum, ouabain or black widow spider venom, either in the presence or in the absence of extracellular Ca2+. The numbers of synaptic vesicles, coated vesicles and coated pits, and the length of axolemma and area of axoplasm were measured on the micrographs. There was a significant increase (about threefold) in the total number of coated structures (vesicles plus pits) per micron2 of axoplasm, but the fractional increase in the number of coated pits exceeded the fractional increase in the number of coated vesicles. These increases were positively correlated with the increase in the length of axolemma per unit area and negatively correlated with the changes in concentration of synaptic vesicles, suggesting that they were due to the increases in the surface area of the terminal that accompany a loss of vesicles. However, the increase in the concentration of coated structures was not related to the number of quanta secreted or to the estimated number of vesicles recycled. The lack of correspondence between the fractional increases in the coated pits and coated vesicles and the poor correlation between the numbers of these structures and the overall parameters of the secretory process suggest that, in contrast to the situation in other secretory systems, coated pits and coated vesicles may not play a crucial role in maintaining the functional population of synaptic vesicles at rapidly secreting neuromuscular junctions. PMID- 2887640 TI - Changes in the dimensions of release sites along terminal branches at amphibian neuromuscular synapses. AB - The probability of transmitter secretion from release sites declines along the length of most long terminal branches (greater than 78 micron) at toad (Bufo marinus) neuromuscular junctions; in contrast, few short terminal branches (less than 78 micron) show such a decline. The present study was carried out to see if any of the dimensions of release sites change along the length of terminal branches in a way that can be correlated with the decrease in secretion probability. The size of presynaptic release site structures was determined by examining serial transverse sections through entire terminal branches with the transmission electron microscope; the size of postsynaptic release site structures was determined by examining terminal gutters with the scanning electron microscope after the removal of terminal branches. Long terminal branches showed a significant decrease in the length of their synaptic contact and cross-sectional area (terminal size) with distance from the origin of the branch. In contrast, there was no significant difference in the length of close apposition (less than 0.2 micron) between the nerve terminal and postsynaptic muscle membrane; furthermore, neither the length of postsynaptic folds nor the frequency of the folds along the length of the terminal gutter changed. Short terminal branches showed no significant differences in the dimensions of either presynaptic or postsynaptic release site structures. The decline in the length of synaptic contacts whilst the length of close apposition remains relatively constant is due to the progressive encroachment of Schwann cell processes between presynaptic and postsynaptic membranes along the length of long terminal branches. PMID- 2887642 TI - P-glycoprotein in human sarcoma: evidence for multidrug resistance. AB - Overexpression of an immunologically conserved, cell-surface glycoprotein (P glycoprotein) is consistently associated with multidrug resistance in cell lines in vitro. A preliminary survey of specimens from 12 solid tumor types in our laboratories indicates significant overexpression of P-glycoprotein in some sarcomas. When tested by immunoblotting with monoclonal antibodies directed against P-glycoprotein; tumors from six of 25 sarcoma patients displayed elevated levels of P-glycoprotein. Three of the sarcoma patients exhibiting P-glycoprotein had not previously been exposed to chemotherapy, implying that overexpression of this marker and possible concomitant multidrug resistance may not depend only on selection during prior drug treatments. The P-glycoprotein overexpression in the sarcoma specimens is evidence for the presence of multidrug resistant cells in these tumors; thus, our data suggest that this mode of resistance may have clinical significance in sarcoma patients. PMID- 2887643 TI - Tyrosine hydroxylase immunoreactivity in the rhesus monkey retina reveals synapses from bipolar cells to dopaminergic amacrine cells. AB - The synaptic organization of dopamine-containing amacrine cells in the rhesus monkey retina was studied using immunohistochemistry of tyrosine hydroxylase (TH), the rate-limiting enzyme in the catecholamine synthetic pathway. Cell bodies of the TH-containing neurons were primarily in the innermost tier of the inner nuclear layer. Their synaptic processes, confined to the outermost stratum of the inner plexiform layer, contained mostly small, clear vesicles and were presynaptic to unlabeled amacrine cell processes and cell bodies at junctions that were symmetrical. Synapses onto the TH-immunoreactive neurons were from bipolar cell axon terminals, nonimmunoreactive amacrine cell processes, and other TH-containing amacrine cells in a decreasing order of predominance. The bipolar cells were presynaptic to the TH-containing neuronal processes at ribbon synapses. The size, structure, and position of the bipolar cell axon terminals, which, like the TH-reactive processes, were narrowly confined to the outermost stratum of the inner plexiform layer, indicate that they are recently described giant bistratified bipolar cells. The identification of this bipolar cell input now provides evidence for a pathway from the outer plexiform layer to dopaminergic amacrine cells in the inner plexiform layer via a type of cone bipolar cell. PMID- 2887641 TI - Phase I trial of taxol given as a 24-hour infusion every 21 days: responses observed in metastatic melanoma. AB - Taxol, a plant product, has significant activity against certain rodent and human xenograft tumors. It promotes microtubule assembly in vitro, in contrast to vinca alkaloids, which inhibit assembly. In this phase I study, taxol was administered as a 24-hour continuous intravenous (IV) infusion in 65 courses to 26 patients. A premedication regimen of dexamethasone, cimetidine, and diphenhydramine was used to prevent the acute hypersensitivity reactions observed in previous studies of taxol. Only one episode of mild stridor occurred in this study. Peripheral neuropathy was the dose-limiting toxicity and was observed in 40% of patients treated at a dose of 250 mg/m2. Significant neutropenia of brief duration was also common. Pharmacokinetic studies by a high-performance liquid chromatography (HPLC) method demonstrated that drug plasma concentrations increased during the 24-hour infusion and then declined rapidly. Peak plasma concentrations correlated with dose, and less than 5% of taxol was excreted in the urine. Most of the drug was bound to serum components. Partial responses of more than 3 months' duration were observed in four of 12 melanoma patients treated. The recommended phase II dose of taxol on this schedule is 250 mg/m2. Priority should be given to the study of taxol in melanoma. PMID- 2887646 TI - Analgesia and anesthesia in neonates. PMID- 2887644 TI - Spinal monoaminergic receptors mediate the antinociception produced by glutamate in the medullary lateral reticular nucleus. AB - Focal electrical stimulation and microinjection of the excitatory amino acid glutamate in the lateral reticular nucleus (LRN) both inhibit the heat-evoked tail flick (TF) reflex in rats. The stimulation-produced inhibition from the LRN has previously been demonstrated to be mediated by spinal monoaminergic receptors. In the present study, inhibition of responses to noxious thermal stimuli by glutamate microinjected into the LRN was examined and characterized; this study is the first to examine the spinal receptors mediating inhibition produced by selective activation of cell bodies in the LRN. Microinjection of glutamate (100 mM) into the LRN in rats lightly anesthetized with pentobarbital produced a transient (less than 5 min) inhibition of the heat-evoked TF reflex, the magnitude of which increased with the volume of glutamate injected (100, 200, or 400 nl). This glutamate-produced inhibition of the TF reflex was antagonized by the intrathecal administration of phentolamine (30 micrograms), yohimbine (15 and 30 micrograms), or methysergide (15 and 30 micrograms) to the level of the lumbar spinal cord, but was not antagonized by prazosin (30 micrograms) or naloxone (20 micrograms). Yohimbine (15 and 30 micrograms) administered to the level of the cervical spinal enlargement did not significantly alter inhibition of the TF reflex produced by glutamate microinjected into the LRN. Microinjection of glutamate (100 mM, 400 nl) into the LRN elevated TF latencies and hindpaw lick latencies in the hot plate test performed on conscious rats. This inhibition of responses to noxious thermal stimuli in conscious rats was short-lasting (less than 5 min), and was also attenuated by intrathecal administration of yohimbine (30 micrograms) or methysergide (30 micrograms), but not by prazosin (30 micrograms) or naloxone (20 micrograms). While it has previously been established that cell bodies in the LRN mediate descending inhibition of spinal nociceptive reflexes, the present results establish that spinal alpha 2-adrenoceptors and serotonin receptors mediate LRN-produced antinociception and extend our understanding of LRN-mediated modulation of nociceptive responses integrated spinally and supraspinally. PMID- 2887647 TI - Vaccination against experimental hepatic amoebic infection--an evaluation of phosphatidylcholine liposomes as immunopotentiator. PMID- 2887645 TI - Excitatory amino acid-induced release of 3H-GABA from cultured mouse cerebral cortex interneurons. AB - A newly developed continuous superfusion model was used for studies of 3H-GABA release from cultured mouse cerebral cortex neurons. It was found that a series of excitatory amino acids (EAAs) representing all receptor subtypes evoked Ca2+- dependent release of 3H-GABA from the neurons. Quisqualate was the most potent agonist tested, with an EC50 value of 75 nM. L-Glutamate, N-methyl-D-aspartate (NMDA), and kainate showed EC50 values of 12, 16 and 29 microM, respectively. The EAA-evoked 3H-GABA release could be blocked by a series of EAA antagonists. The highly selective NMDA antagonist D-2-amino-5-phosphonovaleric acid (D-APV) was found to block NMDA responses, whereas the nonselective antagonists cis-2,3 piperidine dicarboxylic acid (PDA) and gamma-D-glutamyl-aminomethyl sulphonic acid (GAMS) blocked responses to all agonists. NMDA responses were found to be sensitive to Mg+ blockade. EAA- as well as potassium-induced 3H-GABA release from the neurons could be detected as early as day 5 in culture. However, during the culture period up to 12 d, the responses to K+, quisqualate, and NMDA were increased. The ontogenetic development of binding sites for quisqualate, kainate, and NMDA in mouse cortex was studied using the radioligands 3H-alpha-amino-3 hydroxy-5-methyl-4-isoxasole propionate (3H-AMPA), 3H-kainate, and 3H-L glutamate, respectively. The development of binding sites for the different EAA receptor subtypes showed a good correlation with the development of neuronal 3H GABA release evoked by the excitatory amino acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887648 TI - Effects of the alpha 2-adrenergic agonist clonidine and its antagonist idazoxan on the fetal lamb. AB - 1. The alpha 2-adrenergic agonist clonidine was given by aortic injection to three groups of unanaesthetized fetal lambs in utero near term. One group was intact, the second had the brain stem transected just above the pons, and the third had bilateral section of the carotid sinus nerves and cervical vagi. 2. Clonidine had similar effects in all three groups. Electrocortical activity entered a high-voltage, low-frequency episode: breathing, neck and limb movements ceased; arterial pressure remained unchanged or increased; heart rate fell or remained unchanged, and the variation in both heart rate and blood pressure was much reduced. This state lasted 10-20 min, and was followed by a period of up to 4 h during which the cycling of electrocortical activity was rapid and irregular. 3. The alpha 2-adrenergic antagonist idazoxan (0.5-2.0 mg I.A.) blocked all the actions of clonidine. When given alone it usually induced a short period of low voltage electrocortical activity and stimulated breathing movements. These effects were present in both the intact and brain-stem-transected groups, though the stimulation of breathing was significantly reduced by brain-stem transection. There were no consistent effects on heart rate or blood pressure. 4. The effects of clonidine on fetal heart rate and electrocortical activity were similar to those described in adults, but it also had inhibitory effects, not present in adults, on fetal breathing and somatic movements. PMID- 2887649 TI - A permissive role for the vagus nerves in the genesis of antro-antral reflexes in the anaesthetized ferret. AB - 1. The role of the vagus nerves in the genesis of antro-antral reflexes was investigated in the urethane-anaesthetized, splanchnectomized ferret. 2. Antral distension stimulated antral contractions with a threshold volume of 3.5 +/- 0.9 ml (corresponding to an intra-antral pressure of 0.27 +/- 0.11 kPa) by a vagal dependent mechanism as indicated by the attenuated response seen during vagal blockade by cooling. Atropine (1 mg/kg) abolished the antral response to distension. 3. In vagotomized animals, close arterial infusions of acetylcholine at a dose sufficient to return antral motility to basal levels led to the reappearance of the reflex. Low-frequency electrical stimulation of the preganglionic vagal neurones had a similar effect. These effects were also abolished by atropine (1 mg/kg). 4. Hexamethonium (10-25 mg/kg) suppressed the potentiating effect of acetylcholine, indicating a ganglionic site of action. The attenuated response to antral distension seen in vagotomized animals in the absence of exogenous acetylcholine or electrical vagal stimulation was not sensitive to hexamethonium but abolished by atropine (1 mg/kg). 5. The results are consistent with the vagus performing a permissive role in the genesis of antro-antral reflexes mediated through local enteric pathways. PMID- 2887650 TI - [Carpipramine and opipramol poisoning with ventricular tachycardia]. PMID- 2887652 TI - Beta receptor sensitivity testing in humans. PMID- 2887653 TI - Pitfalls in membrane binding sites studies in post-mortem human brain. AB - A number of neurotransmitter receptor sites have been characterized biochemically in post-mortem human brain from normal subjects and in several neurological and psychiatric diseases. Such studies are valid, however, only when appropriate pre mortem and post-mortem conditions are controlled. The effects of age, pre-mortem agonic conditions, drug therapy and post-mortem delay on the characteristics of five binding sites (alpha-1, alpha-2 and beta adrenergic receptors, 5HT-2 serotoninergic receptors, imipramine binding sites) were studied. Age related changes in receptor number were found. Pre-mortem anoxia and hypovolemia had no influence on receptor characteristics. The drugs administered before death, in particular neuroleptics, were found to affect binding to some receptors in post mortem tissue. A post-mortem delay up to 24 hours after death had no effect on binding sites. Experimental strategies (single point values or saturation curves) were also compared. PMID- 2887651 TI - The mammalian beta-adrenergic receptor: structural and functional characterization of the carbohydrate moiety. AB - Mammalian beta-adrenergic receptors are glycoproteins consisting of a single polypeptide chain of Mr approximately 64,000. Treatment of purified [125I] labeled hamster lung beta-adrenergic receptor with alpha-mannosidase reveals two discrete populations of receptor consistent with previous studies using membrane bound photoaffinity-labeled receptor. Treatment of the [125I]-labeled receptor with endoglycosidase F results initially in the formation of a Mr approximately 57,000 peptide which is further converted to Mr approximately 49,000 suggesting that there are two N-linked carbohydrate chains per receptor polypeptide. Exoglycosidase treatments and lectin chromatography of the [125I]-labeled receptor reveals the presence of two complex type carbohydrate chains (approximately 10% of which are fucosylated) on approximately 45% of the receptors. The remaining approximately 55% of the receptors appear to contain a mixture of carbohydrate chains (possibly high mannose, hybrid and complex type chains). Deglycosylation of the receptor by endoglycosidase F does not appear to alter the binding affinity of the receptor for a variety of beta-adrenergic agonists and antagonists. Moreover, the ability of control, alpha-mannosidase sensitive or insensitive (fractionated on immobilized wheat germ agglutinin) and neuraminidase, alpha-mannosidase or endoglycosidase F treated receptors to interact with the stimulatory guanine nucleotide regulatory protein in a reconstituted system were virtually identical. The deglycosylated receptor was also unaltered in its heat lability as well as its susceptibility to a variety of proteases. These findings demonstrate that the carbohydrate portion of the beta receptor does not contribute to determining either its specificity of ligand binding or coupling to the adenylate cyclase system. PMID- 2887654 TI - Repeat ileocolonoscopy in reactive arthritis. AB - Ileocolonoscopy on patients with HLA-B27 related disease, reactive arthritis and ankylosing spondylitis (AS) with peripheral arthritis, revealed the presence of inflammatory lesions in biopsy specimens from the ileum in 71 and 60% of the cases, respectively. A 2nd ileocolonoscopy was performed on 14 patients, 4 to 22 months after the first. In 6 of the 7 patients in articular clinical remission, the inflammatory gut lesions had disappeared. The gut biopsies of the 7 patients with active joint disease continued to show inflammatory lesions. One of these patients underwent a 3rd ileocolonoscopy after having gone into clinical remission, possibly secondary to treatment with sulfasalazine; the histology was completely normal. The strong relationship between clinical articular inflammation and gut inflammation seems to support the hypothesis that in B27 related diseases, repetitive exogenous triggering causing transgression of oral tolerance by increased gut permeability, provokes and maintains the joint inflammation. PMID- 2887655 TI - Sulfasalazine in "intractable" rheumatoid arthritis. PMID- 2887656 TI - Synthesis and activity profiles of new dermorphin-(1-4) peptide analogues. AB - A new series of 12 dermorphin tetrapeptides, W-Tyr-D-MetO-Phe-Xaa-Y (W = H, H2NC = (NH); Xaa = Gly, Sar, D-Ala; Y = OH, OCH3, NH2) were prepared by traditional methods in solution and tested for opioid activity. In binding studies based on displacement of mu, delta, and kappa opioid receptor selective radiolabels from guinea pig brain membranes, the new analogues showed a negligible affinity for the kappa binding site and a preference for mu- over delta-receptors with an evident dependence on N- and/or C-terminal modifications; H-Tyr-D-MetO-Phe-Gly OCH3 was shown to be one of the most selective mu-receptor ligands reported to date. All these tetrapeptides display dose-related naloxone-reversible antinociceptive effects following intracerebroventricular (icv) or subcutaneous (sc) administrations in mice. In comparison to morphine, H-Tyr-D-MetO-Phe-Sar-NH2 and the guanidino derivative H2NC = (NH)-Tyr-D-MetO-Phe-Gly-NH2 showed lower affinity for mu, delta, and kappa sites but exceptionally stronger analgesia: respectively they are 560 and 1550 times as potent an analgesic as morphine. Among analogues tested after sc administration, H-Tyr-D-MetO-Phe-Sar-NH2 and H Tyr-D-MetO-Phe-D-Ala-OH displayed the highest activities; they were respectively 22 and 30 times more potent than morphine on a molar basis. These results indicate that N- or C-terminal modifications and substitution at position 2 or 4 of dermorphin-(1-4) peptide do not only influence the affinity of the resulting analogues to opioid receptors but also may favorably alter their pharmacokinetic properties. PMID- 2887657 TI - Alpha 2-adrenergic agonists/antagonists: the synthesis and structure-activity relationships of a series of indolin-2-yl and tetrahydroquinolin-2-yl imidazolines. AB - The synthesis and alpha 2-adrenergic activity of a series of indolin-2-yl and tetrahydroquinolin-2-yl imidazolines are described. The indolin-2-yl imidazoline 4b was found to possess potent alpha 2-adrenergic agonist and antagonist activity. The modification of the substituents on the indoline ring of 4b has led to the separation of these activities. Substitution on the aromatic ring of 4b with halogen or increasing the size of the N-alkyl substituent of 4b gave alpha 2 adrenergic antagonists without agonist activity. The N-allylindoline 4d is more potent than idazoxan in vitro and is equipotent in vivo, but is less receptor selective (alpha 2 vs. alpha 1) than idazoxan. The cis-1,3-dimethylindolin-2-yl imidazoline 6a is an alpha 2-adrenergic agonist equal in potency to clonidine in vitro, while the trans-1,3-dimethylindolin-2-yl imidazoline 6b is a moderately potent alpha 2-adrenergic antagonist. PMID- 2887658 TI - Carbostyril derivatives having potent beta-adrenergic agonist properties. AB - Derivatives carrying a substituent in the para position of the phenyl group of 8 hydroxy-5-[2-[(1-phenyl-2-methylprop-2-yl)amino]-1-hydroxyethyl] carbostyril (10) were prepared and their effects on beta-adrenoceptors evaluated in vitro. Unsubstituted compound 10, iodo 11, amino 12, and bromoacetamido 13 derivatives (all racemic) bound to the receptor with 15-100-fold lower dissociation constants than that of (-)-isoproterenol. All the above compounds stimulated adenylate cyclase more potently than (-)-isoproterenol. The intrinsic activities of compounds 10 and 12 were equal to that of (-)-isoproterenol. The intrinsic activities of compounds 11 and 13 were 1.3 and 1.2 times that of (-) isoproterenol, respectively. Treatment of membrane preparations with bromoacetamido derivative 13 resulted in an irreversible loss of binding sites, and thus, 13 seems to be an alkylating affinity label for beta-adrenoceptors. PMID- 2887660 TI - Overview of pharmacotherapy: current status and future directions. PMID- 2887659 TI - Charged analogues of chlorpromazine as dopamine antagonists. AB - Chlorpromazine (1, CPZ) is a potent dopamine antagonist that has been used widely as an antipsychotic agent. Since dopaminergic antagonists, like dopaminergic agonists, exist in solution as the charged and uncharged molecular species, it is not clear which form of the amine is most important for interaction with the dopamine receptor. Previous work from our laboratory has indicated that a variety of permanently charged species could replace the amine/ammonium moiety of dopamine and retain dopamine agonist activity. This paper describes the synthesis and dopamine antagonist activity of both the trimethylammonium iodide and the dimethylsulfonium iodide analogues of chlorpromazine. The permanently uncharged methyl sulfide analogue was also synthesized; however, due to its lack of aqueous solubility, its pharmacological activity could not be evaluated. Binding of both the dimethylsulfonium iodide and the trimethylammonium iodide analogues to D-2 dopamine receptors of rat striatal tissue was observed. The observed relative order of binding was CPZ greater than CPZ sulfonium analogue greater than CPZ ammonium analogue. These compounds had a similar order of activity in antagonizing the apomorphine-induced inhibition of potassium-induced release of [3H]acetylcholine from mouse striatal slices. PMID- 2887661 TI - The effect of neuroleptics on cognition and diagnosis, and their influence on stereotypies. PMID- 2887663 TI - Regulation of sterol synthesis and of 3-hydroxy-3-methylglutaryl coenzyme A reductase by lipoproteins in glial cells in primary culture. AB - Although plasma lipoproteins have been demonstrated to have a major role in regulating cholesterol biosynthesis in extraneural cells, no data concerning such regulation are available for developing brain, when cholesterol synthesis is especially active. Glial primary cultures derived from neonatal rat brain and by morphological and biochemical criteria essentially exclusively composed of astrocytes were utilized to examine such regulation. When the primary cultures, which had been maintained in 10% fetal calf serum, were placed in 10% lipoprotein poor serum on day 7 of culture, an induction of sterol synthesis (1.6-2.2-fold) and of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase-specific activity (1.5-2-fold) resulted after 24 hr. Addition of low-density lipoprotein (LDL) to the 10% lipoprotein-poor serum prevented the induction of both sterol synthesis and HMG-CoA reductase. However, addition of high-density lipoprotein (HDL) to the 10% lipoprotein-poor serum caused a 1.5-2-fold further induction of sterol synthesis relative to that in cultures containing 10% lipoprotein-poor serum alone. In contrast to the glial primary cultures, cultures of C-6 glioma cells responded to replacement of 10% fetal calf serum with 10% lipoprotein-poor serum with much more marked increases of sterol synthesis and HMG-CoA reductase. Although, as with the primary cultures, addition of LDL to the C-6 glioma cell cultures prevented the increases in sterol synthesis and reductase activity, addition of HDL had no effect. Thus, these results indicate that in developing glial cells in primary culture, cholesterol synthesis and HMG-CoA reductase are capable of responsiveness to both LDL and HDL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887662 TI - Effects of coculture on the morphology of identified raphe and substantia nigra neurons from the embryonic rat brain. AB - The substantia nigra (SN) is one of the earliest targets of the 5-HT neurons of the raphe nuclei (RN). To test the hypothesis that embryonic 5-HT and catecholamine neurons may influence the differentiation of their target cells or source neurons, we have produced dissociated cell cultures from embryonic day 14 (E14) rat rhombencephalon (containing the serotonergic RN) and mesencephalon (containing the dopaminergic substantia nigra, SN). These cells were grown for 6 days in vitro, either as single cultures (RN or SN) or cocultures (RN + SN). Effects of coculture on the morphological development of neurons immunoreactive (IR) for 5-HT or tyrosine hydroxylase (TH) were studied by measuring a series of morphological parameters related to size of the cell body and dendritic field, as well as to the complexity of neurites within this field, using computer-assisted morphometry. Increases in a number of these parameters were found in cocultures compared to single cultures for both types of monoamine neurons, but a greater number of parameters were increased for TH-IR cells, including size of the cell body. Although this might suggest that there was a greater effect of coculture on the TH-IR (dopaminergic) cells of the SN than on the 5-HT-IR cells of the RN, we must consider the fact that a significant population of TH-IR cells were present in single RN cultures, which contributed to the total population of TH-IR cells in cocultures. Indeed, when morphometric parameters for TH-IR cells in RN and SN single cultures were compared, it was found that TH-IR cells from the RN were generally larger and more complex than those from the SN. Therefore, an analysis was made of which parameters were significantly increased for TH-IR cells in cocultures compared to single cultures from both SN and RN. This was the case for two parameters: cell body size and absolute field area, indicating that these increases were probably due to the effects of coculture itself rather than to contamination by the larger and more complex TH-IR cells from the RN. It is impossible to ascertain, however, whether this effect was on cells from the RN, SN, or both. Coculture effects on 5-HT-IR cells were easier to analyze, since no such cells were found in single cultures of SN.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2887664 TI - Arachidonic acid inhibits uptake of glutamate and glutamine but not of GABA in cultured cerebellar granule cells. AB - The effects of arachidonic acid (20:4) on the uptake of glutamate were studied in primary cultures of cerebellar granule cells and were compared to cortical neurons and astrocytes. At a dose of 0.005 mM, the glutamate uptake was significantly inhibited in cerebellar granule cells. This inhibition was dose and time dependent. The uptake of glutamate was equally sensitive to 20:4 in primary cell cultures of cortical neurons, whereas the uptake in astrocytes was much less sensitive to 20:4. Glutamine uptake was inhibited by 20:4 in cultured cerebellar granule cells and cerebral cortical astrocytes but was not affected in cerebral cortical neurons. Furthermore, the uptake of gamma-aminobutyric acid was not affected by 20:4 in cerebellar granule cells. PMID- 2887665 TI - Differential effect of mu, delta, and kappa opioid agonists on adenylate cyclase activity. AB - D-Ala2, D-Leu5-enkephalin (DADLE) and dynorphin1-13 (Dyn1-13) inhibited striatal adenylate cyclase activity, both basal and dopamine-stimulated (DA), in rats and guinea pigs. The kappa-agonists bremazocine (BRZ), U-50,488 (trans-3,4-dicloro-N methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide), and U-69,593 (5 alpha, 7 alpha 8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl-1-oxaspiro (4.5)dec-8yl) benzeneacetamide inhibited only the basal adenylate cyclase activity, and such an effect was restricted to guinea pig striatum, an area known to contain a high density of kappa-binding sites. Moreover, BRZ was found to antagonize the inhibitory effect of both DADLE and Dyn1-13 in rat striatum. PMID- 2887667 TI - Bladder vasodilatation and release of vasoactive intestinal polypeptide from the urinary bladder of the cat in response to pelvic nerve stimulation. AB - In the feline urinary bladder blood flow was determined by means of a direct blood flow measurement technique before and during pelvic nerve stimulation. Simultaneous sampling of venous blood from the bladder was performed, and the output of vasoactive intestinal polypeptide (VIP) was determined by means of radioimmunoassay. Maximal stimulation of the pelvic nerves led to a clearcut increase in intravesical pressure and a small but sustained increase of blood flow in the bladder wall. These changes were associated with a drastic increase in VIP output from the bladder, increasing from a control level of 0.2 fmol./min. to 15 fmol./min. during stimulation. The results suggest that VIP might be the neurotransmitter responsible for the vasodilatation in the feline urinary bladder in response to pelvic nerve stimulation. The discrepancy between the moderate blood flow increase and the pronounced increase in VIP-release might, however, indicate that VIP exerts its main effects elsewhere in the bladder than in the vascular bed, for instance the detrusor smooth muscle. PMID- 2887668 TI - Clostridium perfringens as the cause of death of a captive Atlantic bottlenosed dolphin (Tursiops truncatus). AB - A previously healthy captive female bottlenosed dolphin (Tursiops truncatus) died suddenly. At necropsy, Clostridium perfringens was isolated from dorsal muscle, blood, left heart ventricle, thoracic fluid, and abdominal fluid. An identical strain was recovered from pool water. A male dolphin in the same pool had inflicted several "rake" marks on the dorsal surface of the female. Water-borne bacteria probably entered these lesions which served as the focus for anaerobe penetration and spread. PMID- 2887666 TI - Adenovirus proteins associated with mRNA and hnRNA in infected HeLa cells. AB - The proteins that interact with cytoplasmic and nuclear polyadenylated RNA in adenovirus type 5 (Ad5) infection of HeLa cells were examined by UV-induced RNA protein cross-linking in intact cells. The Ad5 100-kilodalton late nonvirion protein (100K protein) was cross-linked to both host and viral polyadenylated cytoplasmic RNA (mRNA). The cross-linking of the 100K protein to mRNA appears to correlate with productive infection, because the protein is not cross-linked to mRNA in abortive infection of wild-type Ad5 in monkey cells (CV-1) even though normal amounts of it are produced. However, when CV-1 cells are infected with Ad5 hr404, and Ad5 mutant which overcomes the host restriction to wild-type Ad5 infection in these cells, the 100K protein is cross-linked to mRNA. To identify and obtain antibodies to RNA-contacting proteins, a mouse was immunized with oligo(dT)-selected cross-linked RNA-protein complexes from Ad5-infected cells and the serum was used for immunoblotting experiments. It was found that in addition to the 100K protein, the Ad5 72K DNA-binding protein is also associated with RNA in the infected cells. The 72K DNA-binding protein is cross-linked to polyadenylated nuclear RNA sequences. These findings indicate that adenovirus proteins interact with RNAs in the infected cell and suggest possible mechanisms for the effects of the virus on mRNA metabolism. PMID- 2887669 TI - Research on humans published in JAMA. PMID- 2887670 TI - Mapping the human genome raises question: which road to take? PMID- 2887671 TI - With current gene markers, presymptomatic diagnosis of heritable disease is still a family affair. PMID- 2887672 TI - Hemodynamic effect of bunitrolol on patients with ischemic heart disease. Comparison with propranolol. AB - Acute hemodynamic changes induced by two beta-blocking agents, bunitrolol and propranolol, in patients with ischemic heart disease were studied. Besides possessing negative chronotropic and inotropic effects which were demonstrated by decreased heart rate (HR), cardiac index (CI) and double product (DP) of the heart, propranolol significantly increased systemic vascular resistance (SVR, 12%, p less than 0.05) and the time constant of left ventricular (LV) isovolumic pressure fall (T, 10%, p less than 0.01). With bunitrolol, no significant changes were observed in indexes reflecting chronotropic and inotropic states of the heart, and CI and DP were essentially unchanged. Only LV systolic pressure (-5%, p less than 0.01), LV end-diastolic pressure (EDP, -17%, p less than 0.01) and T (-10%, p less than 0.05) decreased significantly. Systemic vascular resistance (SVR) decreased, though insignificantly. Myocardial oxygen supply-demand balance in the resting state was not improved by propranolol as evidenced by the fact that CI decreased in proportion to the decline in DP. In contrast, ischemia at rest was apparently improved by bunitrolol because LV wall stress decreased due to the reduction in LV volume which was suggested by the decline in LV systolic pressure and LVEDP while CI remained constant. Improvement of the time constant T might be strong evidence of relief from ischemia. Bunitrolol might be effective even in patients with overt heart failure, especially that due to ischemic heart disease because of its lack of negative inotropic action and its ameliorating effect on ischemia at rest. PMID- 2887675 TI - [Hemorrhagic fever with renal syndrome (Korean hemorrhagic fever)]. PMID- 2887674 TI - [A case report of multiple endocrine neoplasia type 2b]. AB - A 10-year-old girl was admitted displaying a medullary thyroid carcinoma, accompanying neurinomas of the tongue, marfanoid habitus, megacolon, and scoliosis. Although her adrenal glands were found to be unremarkable on both CT and ultrasonogram examination an MIBG scintiscan showed a 131-1 uptake, suggesting the presence of medullary hyperplasia. Remarkable nodal involvement with invasive features witnessed in the upper mediastinum during tertiary surgery four years later, following a total thyroidectomy. The TCT and CEA profiling was not sufficient enough to predict a recurrence. At the present state there is difficulty in providing an early diagnosis; through node dissection, however, is considered to be necessary at time of primary thyroid operation in cases with MEN type 2b. PMID- 2887676 TI - [Surface marker changes in the course of adult T cell leukemia. A case report]. PMID- 2887677 TI - [Chronic adult T-cell leukemia with T4 and T8 positive leukemic cells associated with central diabetes insipidus]. PMID- 2887673 TI - Characterization of neurohormonal changes following the production of the benign and malignant phases of two-kidney, two-clip Goldblatt hypertension. AB - The neurohormonal contribution to high blood pressure was investigated in 9 conscious two-kidney, two-clip Goldblatt (2K2C) hypertensive dogs during evolution of the benign and malignant phases after application of bilateral renal clips (BRC). Serial measurements were taken of the plasma renin activity (PRA), plasma angiotensin I-immunoreactivity (Ang I-ir), plasma angiotensin II-ir (Ang II-ir), renin substrate (RS) catecholamines [epinephrine (Epi) and norepinephrine (NE)] and vasopressin (AVP). Immediately after BRC, the elevation of the blood pressure (86 +/- 3 to 110 +/- 3 mmHg, p less than 0.01) was associated with an increase in heart rate (93 +/- 3 to 114 +/- 9 beats/min, p less than 0.01). These hemodynamic changes were accompanied by increases in PRA, Ang I-ir, Ang II-ir, Epi, NE and AVP. The renin angiotensin system was activated throughout the 3 week period following BRC, as indicated by increases in PRA, Ang I-ir and Ang II-ir. Catecholamines were elevated immediately after BRC, followed by a return toward the control values. AVP underwent a slight but not significant elevation after BRC, which was sustained during the 3 weeks. Production of malignant hypertension was affected by occlusion of one of the adjustable renal clips 3 weeks after BRC. A marked elevation of the blood pressure was associated with significant increases in PRA, Ang I-ir, Ang II-ir, Epi, NE and AVP, compared with the pre occlusion values. In addition, pharmacologic experiments were performed in 6 of 9 dogs. Administration of angiotensin I converting enzyme inhibitor (SQ 14225) reduced the blood pressure both in the benign and malignant phases of 2K2C renovascular hypertension, and a ganglionic blocking agent (hexamethonium) also decreased the blood pressure. However, a specific, vascular acting AVP antagonist failed to reduce the blood pressure significantly. From this study, it seems likely that severe renal ischemia caused by renal clipping caused the activation of the renin-angiotensin and the sympathetic nervous system and elevation of serum vasopressin. However, there are no apparent differences between the benign and malignant phases of renovascular hypertension, except for the marked elevation of neurohormone levels in malignant hypertension. PMID- 2887678 TI - [Adult T-cell leukemia presenting with pancytopenia followed by diabetes insipidus]. PMID- 2887679 TI - Effect of neuropeptides on macrophage mediated cytotoxicity in normal donors and cancer patients. AB - The role of enkephalins, endorphins and other neuropeptides produced by the nervous system in the alteration of immune responsiveness is generally unknown. The present studies were undertaken to investigate the role of these neuropeptides in the modulation of cytotoxicity induced by LPS activated macrophages obtained from normal donors as well as breast cancer and Hodgkins disease patients. When the macrophages from normal donors were pretreated with these neuropeptides for 1 hr prior to co-culturing with target cells, macrophage mediated cytotoxicity was enhanced with 10(-6) M and 10(-8) M of [met] enkephalin, 10(-6) M of [leu]-enkephalin and 10(-6) M and 10(-12) M of alpha endorphin. However, when the macrophages were co-cultured with target cells in the presence of the neuropeptides, it was observed that 10(-6) M and 10(-12) M of alpha-endorphin enhanced cytotoxicity whereas no enhancement in cytotoxicity was observed when [met]-enkephalin or [leu]-enkephalin were added to the cultures. In fact, it appears that 10(-10) M of [met]-enkephalin and 10(-12) M of [leu] enkephalin actually suppressed macrophage mediated cytotoxicity. When the opioid antagonist Naloxone was incubated with the neuropeptides in the presence of the macrophages the enhancement of macrophage killing produced by [met]-enkephalin, [leu]-enkephalin or alpha-endorphin was suppressed. When the breast cancer patients' macrophages were pretreated with these neuropeptides, enhancement in cytotoxicity was observed at 10(-10) M of [met]-enkephalin, and [leu]-enkephalin and at 10(-8) M and 10(-12) M of alpha-endorphin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2887680 TI - [Effects of concomitant drugs on the blood concentration of a histamine H2 antagonist (the 3rd report)--concomitant or time lag oral administration of cimetidine and sucralfate]. PMID- 2887681 TI - [Impressions on the 12th meeting of the Japanese Society of Nursing Research- nursing research and conceptual framework]. PMID- 2887682 TI - Gastric acid, serum gastrin and pepsinogen I and II responses to modified sham feeding in tractable and intractable duodenal ulcers. AB - We defined duodenal ulcers (DUs) not healed within 3 months with H2-antagonists as "intractable", because the recurrence rate of these DUs is higher than that of DUs healed within the same periods, and etiological differences are suggested to exist among these two groups. To verify the pathophysiological differences, gastric analysis including modified sham-feeding (MSF) were performed in 12 intractable, 10 tractable DUs and 5 healthy controls. By MSF stimulation, acid output increased in all subjects and the mean acid output of MSF amounted to about 60% of the tetragastrin maximum. Mean acid output of intractable DU cases was significantly higher than the controls in any stimulatory state and was different only in MSF with tractable DU. No significant changes of serum gastrin were recognized during MSF and both serum pepsinogen I and II are higher in DU cases than the control in basal state, but the two DU groups show no significant difference or increase by MSF or gastrin stimulation. These data suggest that vagal activity of intractable DUs is higher than not only healthy subjects, but tractable DUs and participation of gastrin in the increase of acid output by MSF might be denied. PMID- 2887683 TI - Comparison of cardiovascular effects of SGB-1534 and prazosin, selective alpha 1 adrenoceptor antagonists, in anesthetized dogs. AB - The cardiovascular effects of a novel antihypertensive agent, SGB-1534, and its alpha 1-adrenoceptor antagonism in the renal vasculature were investigated in anesthetized dogs and compared with those of prazosin. The doses of SGB-1534 (1 100 micrograms/kg) and prazosin (3-300 micrograms/kg) were increased by a factor of about 3 and given i.v. in a cumulative way. SGB-1534 produced dose-dependent decreases in systemic (systolic, mean and diastolic) blood pressure (SBP), left ventricular (LV) systolic and end-diastolic pressure, and femoral vascular resistance, accompanied by no changes in heart rate (HR), LVdP/dt max and pressure-rate product. Femoral blood flow tended to increase, but the change was not significant. Renal blood flow and the vascular resistance remained virtually unchanged. Similar results were obtained with prazosin for the cardiovascular parameters tested except diastolic SBP and femoral vascular resistance, in which no significant changes occurred. SGB-1534 and prazosin dose-dependently attenuated renal vasoconstrictor responses to a relatively selective alpha 1 adrenoceptor agonist, phenylephrine (3 or 10 micrograms) given into the renal artery. When the doses that attenuated the vasoconstrictor response to phenylephrine by 50% were compared on a weight basis, alpha 1-adrenoceptor antagonistic activity of SGB-1534 was approximately 25 times more potent than that of prazosin in the renal vasculature of dogs. Both alpha 1-adrenoceptor antagonists showed a significant positive correlation between the systemic hypotensive effects and the alpha 1-adrenoceptor antagonism in the renal vasculature. Thus, it seems that SGB-1534, like prazosin, has a balanced effect decreasing afterload as well as preload and that the hypotension is mainly due to the alpha 1-adrenoceptor antagonism in the peripheral vasculatures. PMID- 2887686 TI - Comparison of susceptibility to phagocytosis by mouse peritoneal macrophages between Corynebacterium renale piliated and non-piliated clones. PMID- 2887684 TI - Stimulatory effect of pentobarbital and some anesthetics on gastric secretion in the continuously perfused stomach in rats under urethane anesthesia. AB - Effects of some anesthetics (pentobarbital, thiopental, alpha-chloralose and urethane) on gastric acid secretion were studied in the continuously perfused stomach in rats. Under urethane anesthesia, pentobarbital, thiopental and alpha chloralose showed a definite stimulation on gastric acid secretion. Pretreatment with atropine or hexamethonium abolished the pentobarbital-induced acid secretion. Pentobarbital and thiopental did not elicit acid secretion in bilateral truncal vagotomized rats. In spinal rats, pentobarbital also stimulated acid secretion, but urethane, which was subcutaneously administered, reduced spontaneous acid output. The present results indicated that some anesthetics could stimulate gastric secretion in the anesthetized rat in contrast to the previously described inhibitory effect in the Shay rat. PMID- 2887685 TI - Comparison of experimental infection in mice of Corynebacterium renale piliated and non-piliated clones. PMID- 2887688 TI - [Academic assemblies for nursing profession. International nursing conference--on cancer care etc]. PMID- 2887687 TI - Mechanism of decline of natural killer cell activity in Corynebacterium parvum treated mice: inhibition by erythroblasts and Thy 1.2+ lymphocytes. AB - Injection of (C57BL/6 X DBA/2)F1 mice with Corynebacterium parvum (CP), iv, resulted in a depression of splenic natural killer (NK) cell activity 7-17 days after treatment. This decline in reactivity was accompanied by an increase in splenic tumor-binding cells and a decrease in cytotoxic tumor-binding cells as evaluated in a single-cell assay. Morphologic analysis indicated that the increased tumor-binding cells following CP injection were due to erythroblasts binding to YAC-1 tumor cells. With the use of a double-fluorescent binding technique, nonlytic tumor-binding cells of CP-treated mice inhibited NK cytotoxicity of normal syngeneic mice by competing with effectors for binding to tumor cells. Removal of erythroblasts by hypotonic shock treatment eliminated this competition and significantly improved the lytic capacity of CP-treated mice, thus indicating that erythroblasts contributed to the suppression of NK activity in these mice. The presence of a second inhibitory mechanism in CP treated mice was found following asialo GM1 treatment or Percoll density gradient separation of erythroblast-depleted CP splenocytes; this inhibitory population was identified as Thy 1.2+ lymphocytes. Further analysis of the mechanism of suppression indicated that it was mediated by a soluble factor. In addition to the presence of suppressor cells, CP-treated mice displayed a decrease in splenic large granular lymphocyte content, which may also contribute to their NK deficiency. PMID- 2887689 TI - [Academic assemblies for nursing profession. A stepboard for better nursing care]. PMID- 2887690 TI - [Academic assemblies for nursing profession. My first presentation at JNA Academic Assembly on Pediatric Nursing]. PMID- 2887691 TI - [Use of beta-adrenoblockers after an operation in the development of functional pulmonary artery stenosis]. PMID- 2887692 TI - [Ambulatory examination of children after operations for cryptorchism]. PMID- 2887694 TI - [A patient with Takayasu arteritis and protein C and AT III deficiency]. AB - A 24-year-old patient was admitted to our hospital because of vertigo, coldness and exercise-dependent pain in the left arm. She reported to have suffered from tuberculosis of the lung and a non-A-non-B hepatitis five years ago. Angiography of the aorta thoracica revealed a complete obstruction of the left arteria (a.) subclavia, stenosis of the a. carotis communis on both sides, of the a. carotis interna and the a. vertebralis on the left side as well as a non-detectable perfusion of the upper and medium segment of the left lung. ESR was elevated with 89/128 mm n.W., a hypochromic anaemia, thrombocytosis, hypalbuminaemia, elevation of alpha 2 and gammaglobulins in serum as well as a reduced quick value were found. AT III and protein C concentrations in plasma were also decreased, whereby protein C activity was reduced additionally. HLA-B-51 was positive. Takayasu's arteriitis was diagnosed by us. High-dose treatment with corticosteroids led to a considerable improvement of the clinical status and laboratory parameters of the patient. As this therapy was not associated with a normalization of protein C and AT III concentrations in plasma, protein C and AT III deficiency could be of significance in the development of Takayasu's arteriitis. Until now protein C and AT III deficiency were not described in patients with Takayasu's arteriitis. PMID- 2887693 TI - Alpha 1-antitrypsin gene polymorphism related to respiratory system disease. AB - Restriction fragment length polymorphism (RFLP) in the alpha 1-antitrypsin gene region was studied in relation to chronic obstructive airway disease (COAD) and pneumoconiosis. Genomic DNA of 122 studied subjects was digested with Hind III restriction endonuclease and hybridized with the alpha 1-antitrypsin gene probe. In eight patients with COAD an unusual 10-kb restriction fragment was found hybridizing with the probe. Three of 70 patients were homozygotes for this variant allele and 5 were heterozygotes, showing the presence of two fragments, 2.7 kb and 10 kb. The presence of 10-kb restriction fragment seems to be related to the early development of COAD in studied subjects and therefore might be used as a genetic marker of the disease. PMID- 2887695 TI - [Endocrine cells of the gastrointestinal tract]. PMID- 2887696 TI - [25th international Red Cross congress. A look from the inside]. PMID- 2887697 TI - [Clinical aspects and therapy of drug hypersensitivity]. PMID- 2887698 TI - Vagal release of serotonin into gut lumen and portal circulation via separate control mechanisms. AB - The mechanisms controlling vagally induced serotonin-like immunoreactivity (5 HTLI) release into portal circulation and jejunal lumen were studied in individual cats. In control animals, electrical vagal nerve stimulation significantly enhanced both the endoluminal secretion rate of 5-HTLI and the release of 5-HTLI to the portal vein. The vagally induced release of 5-HTLI to the portal circulation was blocked by pretreatment with propranolol or phenoxybenzamine, or by prior removal of the superior cervical ganglia, but was not blocked by atropine or hexamethonium. On the contrary, the luminal secretion of 5-HTLI after vagal stimulation was not blocked by adrenoceptor blocking agents or ganglionectomy, but instead was inhibited by cholinoceptor antagonists. Thus, in the same experimental animal it was shown that vagally induced release of 5 HTLI to the portal circulation was mediated by adrenoceptor mechanisms, while the luminal release of 5-HTLI was regulated via cholinoceptors. Based on indirect estimations, the apical release of 5-HT seems to be qualitatively small in comparison with the release into the portal circulation. PMID- 2887699 TI - Activity of some benzodiazepine receptor ligands with reduced sedative and muscle relaxant properties on stress-induced electrocorticogram arousal in sleeping rats. AB - Arousal of the electrocorticogram induced by intermittent footshocks in sleeping rats was originally developed to detect hypnotic compounds. A modified shortened protocol is described in which a 2.5-hr nonstressed control period is followed by drug or vehicle administration and a further 5.5-hr recording of the electrocorticogram in the presence of intermittent footshock. The arousal induced by the footshock is reversed by the benzodiazepine chlordiazepoxide and by agents that displace brain benzodiazepine binding but that do not possess the muscle relaxant and sedative properties of benzodiazepines (CL218872, premazepam, ZK91296, RU 43028, and CGS9896). Nonstressed arousal during normal waking was reduced to only a small extent by chlordiazepoxide or any of the other agents tested, suggesting that the footshock-induced arousal is sensitive to the anxiolytic properties of such agents. PMID- 2887700 TI - Histamine H1-receptor antagonist activity assessed in conscious dogs. AB - A simple, minimally invasive technique is described which allows assessment of histamine H1-receptor antagonist activity in conscious dogs. The technique is based on the inhibition of the tachycardia caused by intravenous administration of the H1-receptor agonist, 2-pyridylethylamine. The response to 2 pyridylethylamine is dose dependent and is inhibited, in a dose-dependent manner by H1-receptor antagonists, such as temelastine, terfenadine, and chlorpheniramine. In contrast, cimetidine does not inhibit this response. This technique allows comparison of antagonist activity after either oral or intravenous administration of antagonists and also permits an assessment of the time course of antagonism. PMID- 2887701 TI - Quantitative assessment of central beta 1- and beta 2-adrenoceptor regulation using CGP 20712 A. AB - The use of 100 nM CGP 20712 A (1-[2-((3-carbamoyl-4-hydroxy)phenoxy)ethylamino]-3 [4-(1-methyl-4- trifluoromethyl-2-imidazolyl)phenoxy]-2-propanol methanesulfonate), a specific beta 1-adrenoceptor antagonist, in an in vitro [3H]dihydroalprenolol binding assay simplified the detection of drug-induced alterations in central beta 1- and beta 2-adrenoceptor density. Injection of rats with DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride), a selective noradrenergic neurotoxin, caused an increase in neocortical and hippocampal beta 1-adrenoceptor density. Subchronic infusion of desipramine, a noradrenaline uptake inhibitor, effected a decrease in neocortical and hippocampal beta 1-adrenoceptor density. Subchronic infusion of clenbuterol, a centrally acting beta-adrenoceptor agonist, appeared to decrease striatal beta 2 adrenoceptor density. The results are discussed in terms of the quantitation and regulation of central beta-adrenoceptors. PMID- 2887702 TI - Computerized evaluation of Valsalva's Maneuver before and during alpha adrenoceptor blockade with alfuzosin. AB - Methodological differences exist in the evaluation of Valsalva's Maneuver. Linear and nonlinear mathematical models were described for beat-to-beat changes in blood pressure and R-R intervals occurring during the strain and release phases of Valsalva's Maneuver. This study indicated that the strain phase is linear, whereas the release phase is nonlinear; the release phase consists of a "lag phase," a "breakpoint," and an "overshoot phase." The alpha-adrenoceptor antagonist, alfuzosin, reduced baroreflex-mediated tachycardia during the strain phase and prolonged the "time lag" and "pressure lag" during the release phase; the latter change was due entirely to the reduced systolic pressure that occurred with alfuzosin at the end of the strain phase. PMID- 2887704 TI - Internal mammary artery graft. PMID- 2887705 TI - [Perthes disease and the development of the acetabulum]. PMID- 2887706 TI - [Results of Ender nailing in pertrochanteric fractures (analysis of 1462 cases)]. PMID- 2887703 TI - The use of ex vivo platelet aggregation to confirm the in vivo alpha 2 adrenoreceptor antagonist effect of idazoxan in man. AB - The aggregation of human platelets induced by adrenaline has been used as a test system to investigate the in vivo effect of the alpha 2-adrenoreceptor antagonist idazoxan during initial intravenous studies with increasing doses. The inhibitory effect of idazoxan in vitro was confirmed; addition of idazoxan to platelet suspensions prior to adrenaline caused a competitive inhibition of the aggregatory response by specific antagonism of the platelet alpha 2 adrenoreceptor. Following intravenous infusions of increasing doses of idazoxan to volunteers, a dose-dependent inhibition of the ex vivo aggregatory response to adrenaline was observed in isolated platelet suspensions compared to predose values. The inhibitory effects of idazoxan in vivo declined in a biphasic manner with a more rapid fall over the first hour. This reflects the kinetics of the drug in plasma and the semilogarithmic nature of the concentration-response line observed in vitro. Intravenous doses of 100 and 300 micrograms/kg were demonstrated to be effective antagonist doses of the platelet alpha 2 adrenoreceptor in healthy volunteers. PMID- 2887707 TI - [Meniscus reinsertion in the surgical correction of fresh knee-joint instability]. PMID- 2887708 TI - [Aseptic necrosis of the metatarsal head and results of surgical treatment]. PMID- 2887710 TI - [Analysis of blood circulation in reimplanted fingers using a gamma camera]. PMID- 2887709 TI - [Changing views on the surgical treatment of injuries of the cervical vertebrae]. PMID- 2887711 TI - [The effect of induced synovitis on the blood circulation in the femur head]. PMID- 2887712 TI - [Reconstruction of gliding surfaces of the hand]. PMID- 2887713 TI - [Isolated transient paralysis of the musculus flexor pollicis longus following plate osteosynthesis of the radius]. PMID- 2887714 TI - [The pathological plica mediopatellaris]. PMID- 2887715 TI - [Closure of a complex facial defect using an osteomusculocutaneous flap from the latissimus dorsi]. PMID- 2887716 TI - Effects of H1 blocking agents on age-related osteopenia in the mouse. AB - Old female B6AF1 mice were given acidified tap water, distilled water, one of five H1 blockers or chlorpheniramine (an H1 blocker) and trifluoperazine (a phenothiazine with no H1 blocking activity) in their drinking water for 5 months, and the effects of these agents on bone mineral metabolism were assessed by determining ash weights of femur, ilium and sacrum at the end of the study. In one experiment 24 h whole-body retention (WBR) of Tc 99m methylene diphosphonate (Tc 99m MDP, an indicator of bone metabolism) was measured at the beginning of the study and 40 days later. It was found that: promethazine and dimenhydrinate were the most effective of the H1 blockers in preventing age-related loss of bone mass; distilled water, chlorpheniramine, and chlorpheniramine plus trifluoperazine had no effect on the loss of bone mass; mean bone mass in the groups given meclizine and pyrilamine were greater than but not significantly different from that in the control group given acidified tap water; and only promethazine induced a significant reduction in the WBR of Tc 99m (the other H1 blockers induced small but not significant reductions). PMID- 2887718 TI - [Usefulness of the somatostatin analog SMS 201-995 in the treatment of gastrinoma]. PMID- 2887719 TI - [Do we consume a lot of benzodiazepines?]. PMID- 2887717 TI - Age-related changes of the function of T cell subsets: predominant defect of the proliferative response in CD8 positive T cell subset in aged persons. AB - The proportion of CD8 positive cells in the peripheral blood AET-rosette forming T cells from aged persons was significantly reduced than that from young persons. The difference in the proportion between aged and young groups became more significant after proliferative response to a mitogen phytohemagglutinin (PHA) or a specific antigen tuberculin active peptide (TAP). The purified macrophage deprived T cells (Twp), CD4 (T4) positive cells or CD8 positive cells were prepared from aged or young persons. These cell preparations lost proliferative response to PHA or TAP but showed marked proliferative response to the combined stimulation to 1 microM of ionomycin and 1 nM of phorbol-12-myristate-13-acetate (PMA) at usual culture cell density (2.5 X 10(5)/ml). Proliferative responses of these cell preparations to the combined stimulation were significantly reduced in the aged than those in the young and the magnitude of the difference in the proliferative responses between aged and young groups was more pronounced in CD8 positive cell population than in CD4 positive cell population. Although the cell preparations were relatively independent of exogenous IL-2 for the proliferative response to the combined stimulation of ionomycin and PMA at usual culture cell density, they needed exogenous IL-2 for sustained proliferation at lower culture cell density (5 X 10(3)/ml). These IL-2-dependent proliferative responses to the combined stimulation in the aged were significantly lower than those in the young and again the difference in the proliferative magnitude between aged and young groups was greater in CD8 positive population. The mechanism(s) of age-related change of the proportion and proliferative ability of T subsets were discussed. PMID- 2887720 TI - Treatment of essential hypertension today. The role of beta blockers, calcium antagonists, and ACE inhibitors. AB - The greater sensitivity of echocardiography than electrocardiography has revealed left ventricular hypertrophy (LVH) to occur in a significant minority of patients with systemic hypertension, with the exact prevalence dependent both on how a population is selected and on the sex. race, and possibly age composition of its members. LVH is more closely related to blood pressure recorded in the patient's natural setting during normal activity or exercise--whether measured by portable recorder or home manometer--than to blood pressure measured by the physician. A subgroup of patients with mild essential hypertension exhibit high cardiac output and evidence of supernormal myocardial contractility in the absence of LVH; whereas amongst patients with more sustained hypertension, LVH may be either concentric (associated with high ejection fractions) or eccentric (associated with abnormal responses to exercise). Recent data indicate that echocardiographic detection of LVH identifies mildly hypertensive patients at significant risk, a finding that may aid identification of patients for drug treatment. PMID- 2887721 TI - The adrenergic inhibitors. AB - Although most of the centrally and peripherally-acting adrenergic inhibitors have been available for several years, they continue to contribute importantly to antihypertensive therapy. There are remarkably few contraindications to their use. They are useful in hypertension of all grades of severity, and are also valuable in complicated forms of hypertension, such as those associated with renal insufficiency, diabetes mellitus, and chronic obstructive lung disease. They can produce some fairly predictable side effects in patients, but generally do not cause significant metabolic changes. These drugs also seem to be tolerated well by physically active patients. They appear to have desirable effects on cardiac structure. In general, the adrenergic inhibitors cause regression of a left ventricular hypertrophy, which may well be a valuable property, especially in older hypertensive patients. PMID- 2887722 TI - [Postoperative respiratory failure after parenteral administration of analgesics]. PMID- 2887723 TI - Controlled trial of social work in childhood chronic illness. AB - Children with chronic illnesses have a doubled risk of becoming psychosocially maladjusted, and social-work support and counselling are commonly used to reduce this secondary morbidity. A randomised controlled trial of this type of intervention was conducted in 345 children with chronic physical disorders cared for in eleven specialty clinics at a children's hospital. Four months after a six month period of social-work services, no significant difference was found between social-work and control groups in overall prevalence of maladjustment. There was no evidence to support a preventive or therapeutic effect of social work on child behaviour disorder or social dysfunction on the principal outcome measure, the Child Behaviour Checklist. Nor was there any detectable effect on child self esteem, on maternal psychological function, or on the impact of the child's illness on the family. Furthermore, no patient subgroup could be shown to benefit from the intervention, and restriction of the analysis to individuals who received the intervention did not alter the results. PMID- 2887724 TI - Intrauterine growth retardation: prediction of perinatal distress by Doppler ultrasound. AB - To investigate the ability of umbilical artery Doppler findings to identify true cases at risk of fetal distress among 51 pregnancies clinically judged to be compromised by intrauterine growth retardation (IUGR) Doppler data were related to pregnancy outcome, which was classified into three groups-group 1, healthy babies with normal placental function (16 fetuses), group 2, fetuses with definite signs of placental failure (30), and group 3, non-classifiable pregnancies (5). Group 2 was subdivided into 2A, placental failure with manifest perinatal distress (19), and 2B, placental failure without perinatal distress (11). All 19 compromised and distressed fetuses (group 2A) had extremely pathological Doppler findings, even several weeks before fetal distress became apparent by cardiotocography. The Doppler findings in the 11 small-for-dates fetuses without perinatal distress (group 2B) were inconsistently normal or slightly pathological. All 16 normal infants (group 1) had normal antenatal Doppler data. The Doppler technique thus allows accurate and early recognition of those fetuses who will become distressed perinatally. It also helps to identify which fetuses clinically suspected of IUGR have an adequate placental circulation. PMID- 2887725 TI - Plasmid-mediated resistance to nalidixic acid in Shigella dysenteriae type 1. AB - In an epidemic of shigellosis in southern Bangladesh the causal organism, Shigella dysenteriae type 1, was resistant to nalidixic acid as well as to co trimoxazole (trimethoprimsulphamethoxazole) and ampicillin. The genes coding for resistance to nalidixic acid, but not those coding for resistance to co trimoxazole or ampicillin, are located on a conjugative 20 megadalton plasmid. This epidemic is of particular importance because of the resistance to nalidixic acid, an antibiotic to which shigellae are seldom resistant, and because plasmids were previously thought not to mediate resistance to nalidixic acid. PMID- 2887726 TI - Double-blind trial of yohimbine in treatment of psychogenic impotence. AB - 48 subjects meeting strict diagnostic criteria for psychogenic impotence took part in a 10 week placebo-controlled, double-blind, partial crossover trial of yohimbine (18 mg a day) for restoring erectile function. At the end of the first arm of the trial 62% of the yohimbine group and 16% of the placebo group reported some improvement in sexual function (chi 2 = 10.41, df = 2, p less than 0.05). 21% of the originally placebo-treated group noticed some improvement over pre treatment levels when they were put on yohimbine in the second arm of the trial. Overall 46% of those who received yohimbine reported a positive response to the drug, a response rate very similar to that observed in a previous study of patients with organic impotence. Response to yohimbine thus seems to be unrelated to current groupings of the cause of impotence. Yohimbine is a safe treatment for psychogenic impotence that seems to be as effective as sex and marital therapy for restoring satisfactory sexual functioning. PMID- 2887727 TI - Preimplantation diagnosis of deficiency of hypoxanthine phosphoribosyl transferase in a mouse model for Lesch-Nyhan syndrome. AB - Male mice embryos deficient in hypoxanthine phosphoribosyl transferase (HPRT), derived from heterozygous (carrier) females and normal males, were diagnosed by biochemical microassay of HPRT activity in a single cell isolated from the eight cell preimplantation embryo. The sampled embryos were transferred to recipient mothers and examined on the 14th day of gestation to confirm the accuracy of the preimplantation diagnosis. The diagnosis was sufficiently rapid that freezing of the embryos before transfer was not necessary. Of the embryos diagnosed as HPRT negative all 4 that grew into fetuses were correctly identified as HPRT-deficient males. PMID- 2887728 TI - Pre-eclampsia and trisomy 13: a possible association. AB - Pregnancies of fourteen women who gave birth to babies with trisomy 13 were studied retrospectively for evidence of pre-eclampsia, with twenty-eight controls matched for age and parity. Of the five nulliparous women who subsequently gave birth to a baby with trisomy 13 all had had severe pre-eclampsia, compared with none of the control group. The records of eleven women whose first babies had had trisomy 18 (four) or trisomy 21 (seven) were also studied with appropriate controls and none of these pregnancies had been complicated by pre-eclampsia. Development of pre-eclampsia may be influenced by a gene or genes on fetal chromosome 13. PMID- 2887729 TI - Reye's syndrome and aspirin: epidemiological associations and inborn errors of metabolism. PMID- 2887731 TI - Speech with a cuffed tracheostomy tube. PMID- 2887730 TI - Endoscopic ultrasound--a marriage of inconvenience? PMID- 2887732 TI - What happens to the left ventricle during PTCA? PMID- 2887734 TI - Renal transplantation in children. PMID- 2887733 TI - Prediction of cardiac risk in non-cardiac surgical patients. PMID- 2887735 TI - A role for insulin in the aetiology and course of hypertension? AB - It is proposed that abnormalities of glucose and insulin metabolism have a role in both the aetiology and the clinical course of hypertension. There is resistance to insulin-stimulated glucose uptake in patients with hypertension, which is associated with glucose intolerance and hyperinsulinaemia. Hyperinsulinaemia could contribute to hypertension by stimulating the activity of the sympathetic nervous system and kidney sodium and volume reabsorption. Glucose intolerance and hyperinsulinaemia have been identified as risk factors for coronary artery disease, and their presence may help explain why the frequency of this disease has not been reduced by treatment of hypertension. The fact that several antihypertensive drugs deleteriously affect glucose, insulin, and lipid metabolism makes it even more important to consider these factors in the treatment of high blood pressure. PMID- 2887736 TI - Failure of percutaneous liver biopsy: anatomical variation. AB - Anatomical variation may result in failure to obtain hepatic tissue at liver biopsy. A patient is reported in whom routine liver biopsy was unsuccessful. Subsequent computed tomography (CT) showed that the right lobe of the liver was partially deficient anteriorly and that the biopsy had caused an intraabdominal haematoma. A technically successful biopsy was subsequently carried out under radiological (CT) guidance. Variations in hepatic anatomy are considered and some conclusions are offered which may both improve the success rate and further reduce the morbidity of routine percutaneous needle biopsy of the liver. PMID- 2887737 TI - How psychiatric disorders are missed during medical consultations. AB - There is a strong correlation between patients' scores on a psychiatric screening questionnaire and the number of cues indicative of psychological disturbance that patients give during the medical interview. Verbal cues have the strongest correlation with psychological distress as measured by the questionnaire, but movement cues and postural cues are also important. The reason why some doctors are better able than others to detect psychiatric illness is that they are more likely to allow patients to express verbal and vocal cues. PMID- 2887738 TI - Cost-benefit analysis of hepatitis-B vaccination. AB - Since 1983 the Belgian insurance Fund for Occupational Disease (FOD) has refunded the cost of hepatitis-B (HB) vaccination. Vaccination has been carried out by occupational physicians selectively on staff in hospitals and medical-care institutions. At the end of 1986, 40,000 people at high risk of HBV infection had been vaccinated. The vaccination costs are largely offset by the benefits resulting from the striking fall in the number of HB cases. The financial investment has proved economically beneficial for the insurance fund. PMID- 2887739 TI - Ozone depletion and cancer risk. PMID- 2887740 TI - Sleep apnoea patients have more automobile accidents. PMID- 2887741 TI - Do we need new growth charts? PMID- 2887742 TI - Extracorporeal lithotripsy of gallstones. PMID- 2887745 TI - Worldwide variation in use of chloramphenicol. PMID- 2887744 TI - Enzyme-based chloramphenicol estimation. PMID- 2887743 TI - Prognostic relevance of tumour-cell growth fraction in malignant non-Hodgkin's lymphomas. PMID- 2887746 TI - AIDS and drugs: balancing risk and benefits. PMID- 2887747 TI - Monitoring cocaine epidemics in Barcelona. PMID- 2887748 TI - Psychosis and violence in cocaine smokers. PMID- 2887749 TI - Prescribing for drug addicts. PMID- 2887750 TI - Serotypes of Chlamydia trachomatis in The Gambia. PMID- 2887751 TI - Regional findings in Metsovo lung. PMID- 2887752 TI - Licensed fish-oil concentrate versus cod-liver oil. PMID- 2887753 TI - DNA typing of genital warts and diagnosis of sexual abuse of children. PMID- 2887754 TI - Combination of human fibroblast and immune interferon in chronic active hepatitis B. PMID- 2887755 TI - Effect of activated charcoal on hypercholesterolaemia. PMID- 2887756 TI - HBV/HDV coinfection. PMID- 2887757 TI - Postoperative cardiac death. PMID- 2887758 TI - Aluminium-related bone disease and haemodialysis. PMID- 2887759 TI - Second malignancies and Hodgkin's disease. PMID- 2887760 TI - Immunisation strategy. PMID- 2887761 TI - Skull radiographs after head injury. PMID- 2887762 TI - Cigarette tar reduction. PMID- 2887763 TI - Nicotine chewing-gum. PMID- 2887764 TI - Smoking at work. PMID- 2887765 TI - AIDS, epidemiology, and Africa. PMID- 2887766 TI - AIDS and the African traditional healer. PMID- 2887767 TI - Human immunodeficiency virus isolated from amniotic fluid. PMID- 2887768 TI - Serum thymidine kinase in AIDS patients treated with zidovudine. PMID- 2887769 TI - Coagulation factors and the progress of coronary heart disease. PMID- 2887770 TI - Fibrinolysis and recurrence of myocardial infarction. PMID- 2887771 TI - Relief food and vitamin C deficiency. PMID- 2887773 TI - Improving postgraduate and continuing education. PMID- 2887772 TI - Flumazenil and benzodiazepine withdrawal. PMID- 2887774 TI - Liver transplantation in hepatitis delta virus disease. AB - Seven patients with hepatitis delta virus (HDV) cirrhosis underwent liver transplantation. In every case the HDV infection was florid but accompanied by an inactive hepatitis B virus (HBV) infection. The patients were given anti-HB surface antigen (HBsAg) serum globulins and HBV vaccine. Two patients cleared the HBsAg and the HDV, and are alive and well 14 and 15 months, respectively, after transplantation. HDV infection recurred in the other five patients: hepatitis developed in three, another died, and the fifth was re-transplanted for causes unrelated to viral hepatitis (reinfection was shown by the presence of HD antigen in the graft). Liver transplantation is feasible in patients with HDV disease but involves a high risk of HDV reinfection that cannot be predicted by the virological pattern of the native HBV infection or prevented by conventional HBV prophylaxis. PMID- 2887775 TI - Misuse of intravenous verapamil in patients with ventricular tachycardia. AB - Intravenous verapamil is effective in the acute termination of supraventricular tachycardia but is also used for broad-complex tachycardia when the diagnosis is uncertain. This study analysed the responses to verapamil in 57 episodes of ventricular tachycardia, incorrectly diagnosed as supraventricular tachycardia, in 32 patients. Diagnostic electrocardiographic features of ventricular tachycardia were present in 81% of episodes. Intravenous verapamil (mean dose 9.8 mg) failed to terminate the tachycardia in 45 episodes (79%). 2 patients sustained cardiac arrest after verapamil (1 ventricular fibrillation, 1 asystole), and in 22 episodes severe hypotension occurred. At least one serious adverse effect occurred in 19 patients (59%). Sinus rhythm was restored after verapamil on 10 occasions in 6 patients. Verapamil is ineffective and potentially hazardous in most patients with ventricular tachycardia. It should not be used to treat broad-complex tachycardia unless a supraventricular origin has been established. PMID- 2887776 TI - Successful treatment of primary hyperoxaluria type I by combined hepatic and renal transplantation. AB - A patient with primary hyperoxaluria type 1 (hepatic peroxisomal alanine:glyoxylate aminotransferase [EC 2.6.1.44] deficiency) was successfully treated by combined hepatic and renal transplantation. The metabolic lesion was corrected by replacement of the deficient hepatic enzyme activity. PMID- 2887777 TI - Abnormal vagal function in irritable bowel syndrome. AB - Alimentary and cardiac autonomic nervous function was assessed in 25 patients with the irritable bowel syndrome. The vagally mediated increase in lower oesophageal sphincter pressure induced by abdominal compression was below that of 25 controls in 13 patients. Efferent vagal function, assessed by the ratio of peak acid output after insulin-induced hypoglycaemia to maximal acid output after pentagastrin, was subnormal in 7 of 23 patients. Pulse rate variability with deep respiration was subnormal in 6 of 23 patients. Abnormality in these tests did not correlate closely with the presence of oesophagitis at endoscopy or with that of gastro-oesophageal reflux on pH monitoring. Thus abnormalities in autonomic nervous reflexes might account for the frequent occurrence of gastro-oesophageal reflux and may be involved in the production of disordered gastrointestinal motility in irritable bowel syndrome. PMID- 2887778 TI - A case of disputed maternity. AB - It has been alleged that two Gujarati Muslim boys are not the sons of the woman who brought them to the United Kingdom, claiming them to be her sons. The father has recently died, but blood samples from the mother and her four daughters (whose parentage is not in doubt) allowed the paternal genotype to be deduced. Samples were tested for 9 blood-group systems (12 gene loci), 9 red-cell-enzyme systems, 6 serum protein types, 2 HLA loci, and 5 X-chromosome probes. There was no evidence of non-maternity of the two boys in any of these systems. The odds that the woman who claims to be the boys' mother, rather than any random Gujarati Muslim woman, is indeed the mother of the older boy are fourteen million to one, and that she is the mother of the younger boy five million to one. PMID- 2887779 TI - Aerosolised pentamidine as sole therapy for Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. AB - 15 patients with first episodes of Pneumocystis carinii pneumonia and the acquired immunodeficiency syndrome were treated with only aerosolised pentamidine, which they inhaled for 20 minutes every day for 21 days. 13 of the 15 responded to therapy. Mean PaO2 (mm Hg) and vital capacity (% predicted) were 67.9 and 50.8 before therapy and 80.1 and 67.9 after therapy in patients successfully treated. No systemic side-effects occurred and serum pentamidine concentrations were low in all patients. The only local adverse reaction was cough in 12 patients. Aerosolised pentamidine may be an effective non-toxic treatment for P carinii pneumonia. PMID- 2887781 TI - Poverty, malnutrition, and world food supplies. PMID- 2887780 TI - Microscopic split-skin grafts: a new technique for 30-fold expansion. AB - Split skin was diced into 200 microns squares for use as a graft for large granulating wounds in pigs. "Diced" skin expanded 26-fold to give healing rates virtually identical with those obtainable with meshed split skin, despite a ten fold difference in the area of donor skin used. The technique has been successfully applied in five patients with venous ulcers and seems to be a simple alternative to tissue culture for grafting extensive wounds. PMID- 2887782 TI - Oral anticoagulant control. PMID- 2887783 TI - Neonatal lupus syndrome. PMID- 2887784 TI - Platelet transfusion therapy. PMID- 2887785 TI - In praise of embonpoint. PMID- 2887786 TI - The syndrome of disappearing intrahepatic bile ducts. AB - Diseases with disappearing intrahepatic bile ducts may be developmental, immunological, infective, vascular, or chemical in origin. The immunological group includes primary biliary cirrhosis, graft-versus-host disease, and sarcoidosis. HLA class 2 antigens are displayed on the bileducts and recognition of biliary antigens by cytotoxic T-cells leads to destruction of interlobular ducts. Primary sclerosing cholangitis is associated with immunological features, but the hepatic histology is not that of immunological duct disease. The association with immunodeficiency syndromes, and the finding that secondary sclerosing cholangitis may occur in patients with the acquired immunodeficiency syndrome who are infected with cytomegalovirus, suggest that primary sclerosing cholangitis might be infective in origin. In bacterial cholangitis there is contiguity between the biliary system and the intestinal tract and usually, but not necessarily, partial biliary obstruction. Interference with the hepatic arterial supply to the bileducts leads to vascular cholangitis. Chemical cholangitis follows injection of scolicidal agents into the biliary tree. Diseases with disappearing bileducts have a long natural history and hepatocellular failure occurs late. In the late stages hepatic transplantation gives good results. PMID- 2887787 TI - Enteritis necroticans among Khmer children at an evacuation site in Thailand. AB - A severe illness characterised by bloody diarrhoea and intestinal dysfunction was recognised at an evacuation site on the Thai-Kampuchean border. From June, 1985, to July, 1986, the illness occurred in 62 Khmer children aged 10 months to 10 years (mean 4 years); it was characterised by bloody diarrhoea (94%), fever (90%), and abdominal pain (78%). The overall mortality rate was 58%. Among 16 children who died and underwent necropsy, small-intestinal necrosis of varying severity was found; in 5 of these children small-intestinal lesions with areas of full-thickness necrosis were seen that histologically resembled those in cases of enteritis necroticans (pigbel) in Papua New Guinea. Beta-toxin-producing Clostridium perfringens type C was isolated from 2 of 23 children from whom specimens for anaerobic cultures were collected, and antibodies to beta toxin were detected in 5 of 9 survivors but not in 10 healthy, age-matched control children. These cases show that enteritis necroticans can cause substantial morbidity and mortality outside Papua New Guinea. PMID- 2887788 TI - Mothers and babies in prison. PMID- 2887789 TI - Prognostic significance of atypical epithelial hyperplasia in nipple aspirates of breast fluid. PMID- 2887790 TI - Pharmacokinetic case for giving 6-mercaptopurine maintenance doses at night. PMID- 2887791 TI - Cyclosporin in cadaveric renal transplantation: 5-year follow-up of a multicentre trial. PMID- 2887792 TI - Exchanging kidney transplants. PMID- 2887793 TI - Tetracycline prophylaxis for malaria. PMID- 2887794 TI - Treatment of primary biliary cirrhosis and cholestatic disorders with ursodeoxycholic acid. PMID- 2887795 TI - Opioid-related deaths in Barcelona 1981-86. PMID- 2887796 TI - Folate deficiency and demyelination in AIDS. PMID- 2887797 TI - Home monitoring for infantile apnoea. PMID- 2887798 TI - Serum osmolality in critically ill patients. PMID- 2887799 TI - Cervical cancer screening. PMID- 2887800 TI - Efficient use of cervical screening. PMID- 2887801 TI - Conversion from Bordetella parapertussis to B pertussis. PMID- 2887802 TI - Vaccinating against Japanese encephalitis. PMID- 2887803 TI - Poliovaccination in the Gambia. PMID- 2887804 TI - Methotrexate and retinoids in combination for psoriasis. PMID- 2887805 TI - Comparison of podophyllotoxin and podophyllin in treatment of genital warts. PMID- 2887806 TI - Human papillomavirus frequency in normal cervical tissue. PMID- 2887807 TI - Penicillamine in Indian childhood cirrhosis. PMID- 2887808 TI - Diagnosis of cystic fibrosis. PMID- 2887809 TI - Magnetic resonance imaging in HTLV-1 antibody positive patients. PMID- 2887810 TI - Warning on serum testosterone measurement. PMID- 2887811 TI - Selective binding of bone matrix sialoprotein to Staphylococcus aureus in osteomyelitis. PMID- 2887812 TI - Testing taste. PMID- 2887813 TI - Data sheet warnings about drug safety in pregnancy. PMID- 2887815 TI - British Nutrition Foundation. PMID- 2887814 TI - Product licence for Pregnative Forte F. PMID- 2887817 TI - Generic bioinequivalence. PMID- 2887816 TI - Dietary potassium. PMID- 2887818 TI - Month of birth and rheumatoid arthritis. PMID- 2887819 TI - North Karelia project. PMID- 2887820 TI - Echocardiography and septal thickness. PMID- 2887821 TI - Lowering blood pressure. PMID- 2887822 TI - Treatment for Pneumocystis carinii infection in leukaemia. PMID- 2887823 TI - HIV and health care staff. PMID- 2887824 TI - Role for steroids in treatment of Pneumocystis carinii pneumonia in AIDS. PMID- 2887825 TI - Langerhans cell as primary target and vehicle for transmission of HIV. PMID- 2887826 TI - alpha-Interferon in anti-HIV positive patients. PMID- 2887828 TI - Revised definition of aids. PMID- 2887827 TI - Interference of rheumatoid factor in competitive HIV assay. PMID- 2887829 TI - Transmission of HIV by human bite. PMID- 2887830 TI - Head-down tilt as a physiological diuretic in normal controls and in patients with fluid-retaining states. AB - The effect of the sitting, supine, supine with legs elevated 10 degrees, and 10 degrees head-down tilt postures on renal fluid and electrolyte handling was investigated in 14 patients with hypoalbuminaemic fluid-retaining states and in 14 normal individuals. Basal (sitting) urine volume, creatinine clearance, and urinary electrolyte levels were significantly lower in patients than in controls. In patients the values of these variables increased progressively from the sitting to the supine to the legs elevated to the head-down postures. The percentage rise was higher in patients than in controls, to the extent that, in the head-low position, only creatinine clearance values remained lower in patients than in controls. The head-down posture acts as a physiological diuretic, enhancing diuresis by improving renal function in normal individuals and in patients with ascites and oedema due to hypoalbuminaemia; it also corrects the abnormal fluid and sodium retention in these patients. PMID- 2887831 TI - Carcinoma-in-situ testis in patients with assumed extragonadal germ-cell tumours. AB - Testicular biopsies were done in 15 consecutive patients who were believed to have extragonadal germ-cell tumours. 8 patients (53%) had carcinoma-in-situ (CIS) in the gonads, although none had clinical signs of tumour. In addition, 3 of these patients had small areas of invasive tumour growth. Germ-cell tumours can only be diagnosed as being extragonadal in origin if testicular biopsy appearances are normal. PMID- 2887832 TI - Ploidy as a prognostic determinant in surgically treated lung cancer. AB - The usefulness of tumour ploidy as a prognostic determinant in lung cancer was evaluated in a group of 100 surgically treated patients. Archival paraffin sections of the tumours were analysed by flow cytometry. 45% of tumours were aneuploid and 55% were diploid. Overall, patients with aneuploid tumours had significantly shorter survival (p less than 0.0005) than those with diploid tumours. The subset of patients without nodal involvement at operation and with diploid tumours had a particularly long survival rate. Of these 45 patients 41 (91%) were alive at 2 years compared with only 16 (55%) of the 29 with aneuploid tumours (p less than 0.05). A group with such a favourable prognosis has not previously been recognised except when staging is based on total mediastinal nodal clearance. Ploidy was found to be independent of age, sex, type of operation, site of primary tumour, histology, or TNM category. On Cox multivariate analysis ploidy was the most important and independent prognostic determinant. Therefore, in patients with operable lung cancer, ploidy should be taken into account in planning of management, in estimation of prognosis, and in stratification for treatment trials. PMID- 2887833 TI - Absence of cell surface LFA-1 as a mechanism of escape from immunosurveillance. AB - During studies of T-cell recognition of autologous tumour cells, a number of tumour cell lines derived from patients with lymphoma proved to be poor stimulators of both autologous and allogeneic T-cell responses. Analysis of the tumour cell surface molecules indicated that expression of the lymphocyte function-associated antigen, LFA-1, was lacking, whereas normal leucocytes from these patients expressed normal levels of LFA-1. Examination of other lymphoid tumours revealed that most high grade lymphomas, but not most low or intermediate grade lymphomas, do not express the LFA-1 molecule. Furthermore, in an initial survey, the tumours from 5 of 7 patients with non-relapsing large cell lymphomas expressed LFA-1 whereas only 3 of 18 patients with relapsing lymphomas had tumours that did so. These findings suggest that tumour cells lacking surface LFA 1 cannot initiate an effective immune response in vivo. This lack of immunogenicity might contribute to escape from immunosurveillance. PMID- 2887834 TI - Detection of activated lymphocytes in endocrine pancreas of BB/W rats by injection of 123I-interleukin-2: an early sign of type 1 diabetes. AB - Recombinant interleukin-2 (IL2) was labelled with iodine-123 by a modified chloramine T method. The labelled IL2, which had a high specific activity (100 150 microCi/microgram) and retained its capacity for binding to the IL2 receptor on activated lymphocytes in vitro, was injected intravenously into BB/W diabetes prone and normal rats. Combined immunoperoxidase staining and autoradiography of organ sections revealed that labelled IL2 bound specifically in vivo to IL2 receptor-positive cells in the spleen of both normal and BB/W rats and to activated lymphocytes infiltrating the pancreas of BB/W rats. The severity of lymphocytic infiltration correlated with the degree of radioactivity in the pancreas of BB/W rats. Time-activity curves, generated over organs of injected rats after gamma camera imaging, confirmed that radioactivity was greater in the pancreas of diabetes-prone than in normal rats. 123I is a suitable isotope for gamma camera imaging, so the intravenous injection of IL2 labelled with iodine 123 may be valuable for the in-vivo visualisation of activated lymphocytes in tissues infiltrated by lymphocytes. PMID- 2887835 TI - Pain, anaesthesia, and babies. PMID- 2887836 TI - Carcinoma-in-situ of the testis. PMID- 2887837 TI - The need for asylum for the mentally ill. PMID- 2887838 TI - Steroids in haemorrhagic stroke. PMID- 2887839 TI - Colonoscopy or barium enema as initial investigation of colonic disease. AB - To determine whether double-contrast barium enema (DCBE) or fibreoptic examination should be the first-line investigation for colonic disease 76 consecutive patients presenting for the first time to the outpatient clinic with symptoms of colonic disease deemed to need a DCBE after negative rigid sigmoidoscopy were entered into a trial. All underwent flexible sigmoidoscopy, then DCBE, and finally colonoscopy. 66 patients completed the study. DCBE alone gave the final diagnosis in 42 (67%) and colonoscopy alone in 60 (91%) (p = 0.0004). A combination of flexible sigmoidoscopy and DCBE led to the diagnosis in 50 patients (76%). With DCBE alone 73% of polyps and 64% of patients with inflammatory bowel disease were missed. No complications arose from the investigations. 32 (48%) patients found DCBE distressing and 15 (23%) found colonoscopy uncomfortable (p = 0.004). Its high diagnostic accuracy and relative lack of discomfort for patients make colonoscopy the primary procedure for investigating patients with large bowel symptoms referred to the general surgeon. PMID- 2887840 TI - Induction of puberty by pulsatile gonadotropin releasing hormone. AB - 15 girls and 17 boys with delayed or arrested puberty were treated with gonadotropin releasing hormone (GnRH) for a mean of 1.04 years. GnRH was administered subcutaneously in a pulsatile fashion at 90 min intervals, and the dose was increased as required to maintain progression of puberty, initially only at night and subsequently over 24 h. Initial GnRH dose was 1-2 micrograms per pulse in the girls and 2-4 micrograms per pulse in the boys. The effect of treatment was monitored by serial overnight gonadotropin profiles in all patients and with pelvic ultrasound in the girls. The clinical features, growth acceleration, endocrinology, and ovarian ultrasound morphology of puberty were those seen in normal children. Measurement of spontaneous gonadotropin pulsatility after treatment had been discontinued allowed the distinction between 20 patients with hypogonadotropic hypogonadism and 12 who had constitutional delay of growth and puberty. 2 girls and 6 boys did not respond to the treatment regimen. These findings indicate that normal puberty is GnRH dependent. PMID- 2887841 TI - Two outbreaks of foodborne gastroenteritis caused by a small round structured virus: evidence of prolonged infectivity in a food handler. AB - In two outbreaks of diarrhoea and vomiting that were caused by a small round structured virus (SRSV) that affected over 275 people, epidemiological and laboratory evidence showed that certain foods were the vehicles of infection and suggest that one of the chefs who prepared them may have been excreting this virus for a long time. PMID- 2887842 TI - Hepatitis B vaccine: responder status and timing of additional booster doses. PMID- 2887843 TI - Intradermal hepatitis B vaccine. PMID- 2887844 TI - Maternal rubella: one problem in diagnosis and another in prevention. PMID- 2887845 TI - Epidermal-growth-factor receptors and breast cancer. PMID- 2887846 TI - Rubella vaccination policy. PMID- 2887847 TI - Epidemic rise of coronary heart disease. PMID- 2887848 TI - Minoxidil for male-pattern baldness. PMID- 2887849 TI - Lymphoma in patients taking etretinate. PMID- 2887850 TI - Erythromycin-induced gastrointestinal effects. PMID- 2887851 TI - Prevention of experimental carotid artery thrombosis by magnetic vectoring of aspirin. PMID- 2887852 TI - "Incidental" neuroblastoma. PMID- 2887854 TI - Failure to identify heterozygotes for galactosaemia in women with premature ovarian failure. PMID- 2887853 TI - Screening for neuroblastoma. PMID- 2887855 TI - Cerebral infarction associated with Mycoplasma pneumoniae infection. PMID- 2887856 TI - Tuberculin and 'multitest' skin-tests in drug abusers. PMID- 2887857 TI - Death associated with hyperventilation. PMID- 2887858 TI - Direct catheter fulguration of atrial flutter. PMID- 2887859 TI - Usefulness of a clinical case-definition of AIDS in East Africa. PMID- 2887860 TI - Imaging cerebral damage in HIV infection. PMID- 2887861 TI - Pancreatic lesions in AIDS. PMID- 2887862 TI - Possible involvement of HIV in neuropsychiatric episode in patient seronegative for two (or more) years. PMID- 2887863 TI - Circulating cytotoxic protein generated after ethanol consumption. PMID- 2887864 TI - Pulsed ultrasound therapy and skin blood-flow. PMID- 2887865 TI - Myocardial ischaemia triggers formation of thromboxane. PMID- 2887866 TI - Peripheral versus central intravenous lines in emergency cardiac care. PMID- 2887867 TI - Compulsory admission under National Assistance Act. PMID- 2887869 TI - AIDS, Africa, and academics. PMID- 2887868 TI - Human immunodeficiency virus and the law. PMID- 2887870 TI - Guilt after abortion. PMID- 2887872 TI - Selective reduction in assisted pregnancies. PMID- 2887871 TI - Pesticides and health. PMID- 2887873 TI - Peripartum cardiomyopathy. PMID- 2887874 TI - Diabetic microangiopathy and joint disorders. PMID- 2887875 TI - Prednisolone does not prevent post-herpetic neuralgia. PMID- 2887876 TI - Social-class gradients, specific cause mortality, and accuracy of diagnosis of cause of death. PMID- 2887877 TI - Lack of c-myc gene amplification in genital tumours with different HPV status. PMID- 2887878 TI - Toxic shock syndrome and staphylococcal pneumonia. PMID- 2887879 TI - Low phosphate levels in ventilated patients. PMID- 2887881 TI - Blood viscosity and lowering blood pressure. PMID- 2887880 TI - "Central obesity" and coronary heart disease. PMID- 2887883 TI - Dietary fibre. PMID- 2887882 TI - Measuring alcohol in vapours above the eye. PMID- 2887884 TI - Sign of the Cheshire cat. PMID- 2887885 TI - Reduction of stress/catecholamine-induced cardiac necrosis by beta 1-selective blockade. AB - 114 haemodynamically stable patients with acute head injury were randomised, double-blind, to either placebo or atenolol given intravenously (10 mg every 6 h) for 3 days then orally (100 mg daily) for a further 4 days. Both groups were equally stressed as shown by raised arterial noradrenaline levels. In patients receiving placebo, but not in those receiving atenolol, there was a significant (p less than 0.01) positive correlation between arterial noradrenaline and levels of the myocardial isoenzyme of creatine kinase (CKMB). 30% of the placebo group compared with 7.4% of the atenolol group (p less than 0.05) showed CKMB levels greater than 3% of total creatine kinase (compatible with myocardial damage). CKMB levels greater than 6% of total creatine kinase (compatible with acute myocardial infarction) were present in 16.7% of patients receiving placebo but in no patients receiving atenolol (p = 0.053). Atenolol appeared to reduce significantly the likelihood of supraventricular tachycardia and ST-segment and T wave changes and prevented cardiac necrosis seen at necropsy. PMID- 2887886 TI - Long latency precedes overt seroconversion in sexually transmitted human immunodeficiency-virus infection. AB - Signs of latent HIV infection were sought in stored serum samples collected before overt seroconversion, confirmed by enzyme-linked immunosorbent assay (ELISA), from 9 subjects with human-immunodeficiency-virus (HIV) infection, in serum from 25 seronegative sexual partners of HIV-seropositive men and from 23 other seronegative, homosexually active men. Free HIV antigen and/or low-titre antibodies to recombinant structural (core, env) or non-structural (3' orf, sor, tat) proteins were seen 6-14 months before seroconversion in all 9 subjects who seroconverted. Antibodies against core proteins detected by western blot were usually the first sign of latent HIV infection. 5 of the 25 ELISA-negative exposed partners have shown HIV antigenaemia and antibodies against core proteins for 16-34 months. By in-situ hybridisation, HIV-specific RNA was detected in peripheral-blood non-lymphoid mononuclear cells in some of the latently infected partners. All subjects with latent HIV infection had normal numbers of T4 lymphocytes but half of them lost their in-vitro proliferative T-cell response to a recall antigen (purified protein derivative of tuberculin). Early HIV infection, characterised by a low-level and restricted antibody response towards HIV core and regulatory proteins, seems mainly to affect antigen-presenting cells. PMID- 2887887 TI - Prediction of cerebral palsy in very low birthweight infants: prospective ultrasound study. AB - The value of regular cerebral ultrasound scanning in predicting cerebral palsy (CP) was assessed in very low birthweight infants. The infants were scanned before discharge, and their vision and hearing were assessed at age 9 months and neurodevelopment was assessed at 18 months. Ultrasound abnormalities, defined before the study, were periventricular haemorrhage (PVH), "prolonged flare" (echodensity persisting in the periventricular white-matter for more than 2 weeks without cavitating), and cystic periventricular leukomalacia (PVL). The incidence of these three conditions in surviving infants was 49%, 15%, and 8%, respectively. 158 infants survived to be discharged from hospital and 156 had neurodevelopmental assessment at 18 months of corrected age. All infants with PVH alone and confined to the lateral ventricles were normal at follow-up. The presence of cysts accurately predicted abnormal outcome (94%) and was highly specific (96%). Prolonged flare predicted adverse outcome but the accuracy (79%) was less good than for cystic PVL. 12 infants had CP, and 10 of these had ultrasound evidence of PVL. 8 of the 13 infants with cysts had spastic CP. 4 of these were walking independently and had mild CP. No infant with ultrasound evidence of a single cyst or with cysts confined to the frontal region or centrum semiovale had severe CP. Cysts involving the periventricular white-matter in the occipital region were associated with a poor prognosis. Echolucent cystic lesions detected by ultrasound in the neonatal period accurately predict adverse outcome, and if multiple and present in the occipital region, confer a very high risk of severe CP. PMID- 2887890 TI - Pseudopolycythaemia. PMID- 2887888 TI - Evidence of enhanced lipid peroxidation in the cerebrospinal fluid of patients taking phenothiazines. AB - Products of lipid peroxidation in the cerebrospinal fluid are found in higher concentrations in patients receiving phenothiazines than in control subjects matched for age and sex. Especially high concentrations are found in patients experiencing ill-effects from phenothiazine therapy. Raised concentrations of cerebrospinal fluid "phenanthroline copper" in these patients suggest that metal catalysed mechanisms may promote the lipid peroxidation. It is suggested that lipid-soluble antioxidants, such as vitamin E, may be useful for the prevention and treatment of phenothiazine side-effects. PMID- 2887891 TI - Memory testing: no thermometers available. PMID- 2887889 TI - Antifertility actions of the progesterone antagonist RU 486 include direct inhibition of placental hormone secretion. AB - the antifertility effects of the potent antiprogestin RU 486 (mifepristone) during early pregnancy have been attributed to its blockade of progesterone receptors in the endometrium. Studies in cultured syncytiotrophoblasts have revealed an additional action of RU 486 at the placental level, where it impairs the production of human chorionic gonadotropin (hCG), human placental lactogen (hPL), and progesterone. RU 486 (10 nmol-10 mumol/l) attenuated the production of all three placental hormones, in a dose-related manner, and its effects on hCG and hPL were reversed by addition of exogenous progesterone. The specific inhibitory effects of RU 486 on placental hormone secretion indicate that its antifertility actions are attributable to competitive inhibition of progesterone action in the trophoblast as well as in the endometrium. PMID- 2887892 TI - Food handlers and salmonella food poisoning. PMID- 2887893 TI - Predictive value of exercise electrocardiogram in symptomless subjects. PMID- 2887894 TI - Clostridium septicum and neutropenic enterocolitis. PMID- 2887895 TI - Has the management of asthma improved? AB - Asthma morbidity and mortality are reported to be rising in the UK, despite increased sales of anti-asthmatic drugs. To determine whether recent advances in therapy have been beneficial the results of the 1970-71 and 1981-82 national morbidity surveys in general practice and the Department of Health and Social Security surveys of prescribing for 1968 to 1985 have been examined. Between 1970 71 and 1981-82 the number of asthmatics diagnosed rose by 75%, but, for the average asthmatic, consultation, home visit, and outpatients referral rates fell significantly by 19%, 44%, and 32%, respectively. Over the same period total prescribing for airflow obstruction rose by 76%. The proportion of treatment aimed at attack prevention increased from 10.6% to 19.4%. Thus for the average asthmatic management has improved because fewer consultations are required. Increased use of inhaled topical steroids and sodium cromoglycate is probably responsible for this improvement. Nevertheless preventive treatment remains under prescribed and asthma is still underdiagnosed. PMID- 2887896 TI - Emergency obstetric surgery performed by nurses in Zaire. AB - In rural northwestern Zaire nurses at Karawa and Wasolo hospitals were trained to do caesarean sections, laparotomies, and supracervical hysterectomies. In Karawa 278 of 321 caesarean sections were done by nurse-surgeons in 18 months, with two deaths. In Wasolo all 32 caesarean sections in 13 months were done by the nurse surgeons, with 1 death. Of the 37 laparotomies done in both centres, 16 were by nurse-surgeons, and there were two deaths. Four of the five deaths were attributable to protracted labour with septicaemia (1), postoperative infection (2), and protracted labour with no blood pressure on admission (1). Obstetric operations could safely be performed by specially trained nurses in rural areas of developing countries and the high maternal mortality rate in such areas could thus be reduced. PMID- 2887897 TI - Fate of the vascular patient after below-knee amputation. AB - 50 below-knee amputations were carried out in 45 patients (25 men and 20 women), mean (SD) age 73 (10.5) years. The mean survival time was 22(16) months after the operation. In each patient the healing potential of a below-knee amputation was determined preoperatively by segmental pressure studies and thermographic delineation of skin perfusion. 33 of the stumps healed by first intention, in 14 healing was delayed but occurred without the need for further surgery, and 3 stumps healed after local wedge excision. The initial mobilisation rate was 90%. Thus, there are no grounds for carrying out an initial above-knee amputation to save the patient a further operation. PMID- 2887898 TI - Aspects of violence. PMID- 2887899 TI - Alternative mechanism of action of "anti-oestrogens" in breast cancer. PMID- 2887900 TI - Omeprazole versus ranitidine in erosive oesophagitis. PMID- 2887901 TI - Preservation of kidney function by use of converting-enzyme inhibitors for control of hypertension. PMID- 2887902 TI - Treatment of mild to moderate hypertension with dietary fibre. PMID- 2887904 TI - Granulomatous hepatitis associated with Lyme disease. PMID- 2887903 TI - Islet amyloid polypeptide. PMID- 2887905 TI - Borrelia burgdorferi and Shulman syndrome. PMID- 2887906 TI - Reduction in toxicity of doxorubicin by liposomal entrapment. PMID- 2887907 TI - Decreasing risk of leukaemia during prolonged follow-up after mitobronitol therapy for polycythaemia vera. PMID- 2887908 TI - Reversible cerebellar diaschisis in focal epilepsy. PMID- 2887909 TI - AIDS and drug addicts in Europe. PMID- 2887910 TI - Remission of AIDS-associated psoriasis with zidovudine. PMID- 2887911 TI - Atopic eczema in HIV-seropositive haemophiliacs. PMID- 2887912 TI - HIV transmission from male after only two sexual contacts. PMID- 2887914 TI - Autoimmunity to cardiolipin in infectious mononucleosis. PMID- 2887913 TI - Allopurinol/N-acetylcysteine for carbon monoxide poisoning. PMID- 2887915 TI - Previously undescribed cause of sciatica. PMID- 2887916 TI - Health of gypsies/travellers. PMID- 2887917 TI - Long-term care and the private sector. PMID- 2887919 TI - Ethics of research in childhood malnutrition. PMID- 2887918 TI - Surgical training and overseas doctors. PMID- 2887920 TI - Iatrogenic subglottic stenosis leading to tracheostomy in childhood. PMID- 2887921 TI - Munchausen by proxy or Meadow's syndrome? PMID- 2887922 TI - Uveitis after hepatitis B vaccination. PMID- 2887923 TI - Detoxification of pertussis vaccines. PMID- 2887924 TI - Cryptosporidium and drinking water. PMID- 2887925 TI - Diabetes mellitus and low environmental magnesium levels. PMID- 2887926 TI - Campylobacter pylori and peptic ulcer disease. PMID- 2887927 TI - Spiral organisms in the baboon stomach. PMID- 2887928 TI - Sulphasalazine and oxidant scavenging in ulcerative colitis. PMID- 2887929 TI - Clinical significance of anti-IFN-alpha antibody titres during interferon therapy. PMID- 2887930 TI - Menstrual changes in a patient treated with etretinate. PMID- 2887931 TI - Fish oils as medicines. PMID- 2887932 TI - Interaction of cyclosporin and itraconazole. PMID- 2887933 TI - Transient taste-loss during treatment with etidronate. PMID- 2887934 TI - Hypertension during high-dose ketoconazole treatment: a probable mineralocorticosteroid effect. PMID- 2887935 TI - Mydriatic response to topical naloxone in anorexia nervosa. PMID- 2887936 TI - Diabetes in rural West Africa. PMID- 2887937 TI - Avoidable drug interaction, not meningitis. PMID- 2887938 TI - 1,25-Dihydroxyvitamin D3, the c-myc oncogene, and cell regulation. PMID- 2887939 TI - Prognostic assessment of female fecundity. AB - A clomiphene citrate (CC) challenge test was used to prospectively assess future fertility potential in 51 women aged 35 or more with unexplained infertility. Baseline (day 2-3 of the menstrual cycle) and response levels (day 9-11) of follicle stimulating hormone (FSH), luteinising hormone (LH), and 17-beta oestradiol were measured before and after administration of 100 mg clomiphene on days 5-9 of the menstrual cycle. Although all the women had a normal baseline FSH, 18 had an exaggerated FSH response of 26 mIU/ml or more (over 2 standard deviations above control values); this was regarded as a diminished ovarian reserve (DOR). In the DOR group mean response FSH was 38.9 mIU/ml (SD 13.8) and in 33 women with adequate ovarian reserve (AOR) it was 11.5 (4.9) mIU/ml (p less than 0.0001). In the DOR group 1 of 18 patients and in the AOR group 14 of 33 (42%) conceived (p less than 0.05). It is suggested that despite apparently normal ovulatory cycles, the DOR group has a compromised follicular apparatus. Disparity between normal oestradiol secretory capacity of the granulosa and diminished capacity to secrete inhibin could explain the inappropriately high FSH levels in response to the CC challenge. PMID- 2887940 TI - Haemophilus influenzae type b strains of outer membrane subtypes 1 and 1c cause different types of invasive disease. AB - Of 275 consecutive Haemophilus influenzae type b (Hib) strains isolated from children with invasive disease in Finland in 1985-86, 74% were of the common European outer membrane protein (OMP) subtype 1 and 22% were of OMP subtype 1c, which is usually rare. Strains of subtype 1c caused proportionately more meningitis and less epiglottis than did strains of subtype 1c. Furthermore, children with disease due to strains of subtype 1c were younger than those with disease due to strains of subtype 1. The significant difference in association between subtype and the diagnosis of epiglottitis or meningitis remained even when the strong influence of age was accounted for. This finding may suggest a true difference in the virulence between these subtypes not previously demonstrated for Haemophilus influenzae type b. PMID- 2887941 TI - Placebo-controlled comparison of captopril, atenolol, labetalol, and pindolol in hypertension complicated by intermittent claudication. AB - In a six month placebo-controlled cross-over trial twenty patients with hypertension and peripheral arterial disease were randomised to captopril 25 mg twice daily, atenolol 100 mg once daily, labetalol 200 mg twice daily, or pindolol 10 mg twice daily for one month. Although all treatments were equally effective at lowering blood pressure, pain-free and maximum walking distances on a treadmill were decreased by atenolol, labetalol, and pindolol, but not by captopril. Post-exercise calf blood flow availability was impaired by atenolol, labetalol, and pindolol, but not by captopril. Despite ancillary characteristics of cardioselectivity, intrinsic sympathomimetic activity, or combination with alpha-blockade, beta-blockers seem to impair the lower limb circulation in such patients, whereas captopril seems to preserve it, possibly by maintaining the collateral blood supply. PMID- 2887942 TI - Epithelioid angiomatosis: a distinct vascular disorder in patients with the acquired immunodeficiency syndrome or AIDS-related complex. AB - Unusual cutaneous vascular neoplasms distinct from Kaposi's sarcoma were observed in five patients with the acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 infection. The cutaneous lesions were solitary or multiple papules and nodules. In some patients the lesions also affected internal organs. Histologically the neoplasms were composed of proliferating blood vessels and cells with epithelioid features. Immunoperoxidase studies of one lesion showed that the cells expressed both factor VIII antigen, a maker for endothelial cells, and alpha 1-anti-chymotrypsin, a marker for histiocytes. In some patients the lesions gradually disappeared but in two they were the cause of death, in one case from disseminated intravascular coagulation and in the other from laryngeal obstruction by the tumour. PMID- 2887943 TI - Cholesterol oxides in Indian ghee: possible cause of unexplained high risk of atherosclerosis in Indian immigrant populations. AB - Two populations of immigrants to London and to the West Indies from the Indian subcontinent have higher than expected morbidity and mortality from atherosclerosis but do not show the commonly accepted major risk factors. This study investigated the hypothesis that ghee, a clarified butter product prized in Indian cooking, contains cholesterol oxides and could therefore be an important source of dietary exposure to cholesterol oxides and an explanation for the high atherosclerosis risk. Substantial amounts of cholesterol oxides were found in ghee (12.3% of sterols), but not in fresh butter, by thin-layer and high performance-liquid chromatography. Dietary exposure to cholesterol oxides from ghee may offer a logical explanation for the high frequency of atherosclerotic complications in these Indian populations. PMID- 2887944 TI - Why does antihypertensive treatment prevent stroke but not myocardial infarction? AB - It is proposed that differences in autoregulatory reserve and blood oxygen extraction potential between the coronary and cerebral circulations explain why antihypertensive treatment effectively protects patients against stroke but has failed to reduce the increased incidence of myocardial infarction associated with hypertension. In the brain, oxygen extraction from the blood can be increased if blood pressure falls below the lower limit of autoregulation. In the coronary circulation, however, oxygen extraction is nearly maximum at rest, and lowering of blood pressure by antihypertensive therapy can lead to myocardial ischaemia. PMID- 2887945 TI - Congenital adrenal hyperplasia. PMID- 2887947 TI - Cells, vaccines, and world health. PMID- 2887946 TI - Phytic acid: new doors open for a chelator. PMID- 2887948 TI - Sexing of female athletes. PMID- 2887949 TI - Colchicine myoneuropathy. PMID- 2887950 TI - Human immunodeficiency virus infection and routine childhood immunisation. AB - Current experience with the safety and efficacy of vaccines in infected children and adults is reviewed to examine the basis for decisions about routine immunisations of children infected with the human immunodeficiency virus (HIV). No adverse reactions to inactivated vaccines have been noted, but complications with live vaccines have been recorded with both BCG and smallpox. Limited experience with live poliomyelitis and measles vaccines in HIV-infected children has not yet shown any severe complications from these vaccines. Theoretical concerns that immunisation might accelerate the course of HIV infection are not supported by available data. Serological response to most inactivated and live vaccines is reduced in HIV-infected persons, and is related to the degree of immunosuppression present. Preliminary evidence suggests that the severity of some vaccine-preventable diseases is increased in HIV-infected children. This review finds general support for recommendations on immunisation of HIV-infected children that have been developed by the World Health Organisation. PMID- 2887952 TI - Hepatic transplantation in Europe. First Report of the European Liver Transplant Registry. AB - At the 32 European centres where livers are transplanted the actuarial survival rate for 1218 patients was 44% at 1 year and 41% at 2 years. Perioperative mortality (30 days) was 30%. Recipients aged under 15 years had a higher survival rate than those aged over 15; the differences were 22% at 1 year and 32% at 2 years. For the 97 patients who received two or more liver grafts, actuarial survival was 27.7% at 1 and 2 years. Two-thirds of the transplantations were done since 1984. Since then the best results have been obtained for biliary atresia (88 cases; survival rates at 30 days, 1 year, and 2 years were 87%, 74%, and 68%). Primary biliary cirrhosis was the commonest benign indication for transplantation, with survival of 64% at 1 and 2 years. The proportion of transplantations that were done for patients with hepatocellular carcinoma was smaller after than before 1984; among transplantations done in adults after 1984, those done because of hepatocellular carcinoma gave the best perioperative survival rate (76%) but the worst 2 year survival (30.8%). PMID- 2887953 TI - Some observations on dowsing and the human magnetic sense. PMID- 2887951 TI - Blind evaluation of the effect of octreotide (SMS 201-995), a somatostatin analogue, on small-bowel fistula output. AB - In a blind crossover trial for 4 days, after at least 7 days on conventional treatment, 14 patients with postoperative small-bowel fistula were randomised to 2 days on a somatostatin analogue, octreotide (SMS 201-995), followed by 2 days on placebo (group 1) or vice versa (group 2), after which all patients were treated with octreotide until the fistula closed or reoperation was deemed necessary. In group 2 mean fistula output was reduced from 698 ml per 24 h pretreatment to 246 mg per 24 h after 2 days on octreotide; output increased from 228 ml per 24 h to 497 ml per 24 h when treatment with octreotide was interrupted by placebo. In 11 patients fistulae closed spontaneously in an average of 4.5 days after continous treatment with octreotide. PMID- 2887954 TI - Immunisation with paternal lymphocytes in women with recurrent miscarriage. PMID- 2887955 TI - Person-to-person transmission of Campylobacter pylori. PMID- 2887956 TI - Antibody to Campylobacter pylori in families of index children with gastrointestinal illness due to C pylori. PMID- 2887957 TI - Long-term treatment with azathioprine abolishes thymic lymphoid follicular hyperplasia in myasthenia gravis. PMID- 2887958 TI - Typhoid vaccines. PMID- 2887959 TI - Laser coronary angioplasty under direct vision. PMID- 2887960 TI - Trends in cholecystectomy rates in the United States. PMID- 2887961 TI - Amodiaquine-resistant malaria in Brazil. PMID- 2887962 TI - Echotomographic evidence for a highly endemic focus of hydatidosis in central Tunisia. PMID- 2887963 TI - Negative inotropic effects of famotidine. PMID- 2887964 TI - Motoneurone disease as manifestation of pesticide toxicity. PMID- 2887965 TI - Pulmonary infiltrations induced by tolfenamic acid. PMID- 2887966 TI - Pityriasis versicolor and sunscreens containing coconut oil. PMID- 2887967 TI - HIV infection in polytransfused thalassaemic patients. PMID- 2887968 TI - Relation between elderly and AIDS patients with drug-induced Parkinson's disease. PMID- 2887969 TI - Dihydroneopterin and CNS infections. PMID- 2887970 TI - Pathogenesis of haemolytic uraemic syndrome. PMID- 2887971 TI - Wind of change in the airway. PMID- 2887972 TI - Lactitol, lactulose, and blood ammonia. PMID- 2887973 TI - Cerebral oedema in diabetic ketoacidosis. PMID- 2887974 TI - Chemotherapy for advanced ovarian cancer. PMID- 2887975 TI - Endoscopic versus percutaneous stents for malignant jaundice. PMID- 2887976 TI - Maternal rubella after 18 weeks. PMID- 2887977 TI - Brainstem herpes virus encephalitis. PMID- 2887978 TI - Hepatitis B virus and glomerulonephritis. PMID- 2887979 TI - Innervation of zygapophyseal joint synovial folds in low-back pain. PMID- 2887980 TI - Multiple pregnancy and assisted reproduction. PMID- 2887981 TI - Choroid plexus cysts and trisomy 18. PMID- 2887982 TI - Hypertension in the puerperium. PMID- 2887983 TI - Epidemic pre-eclampsia? PMID- 2887984 TI - Human B-lymphotropic virus in Germany. PMID- 2887985 TI - Loss of life from heart attacks at different ages. PMID- 2887986 TI - How far to lower blood pressure? PMID- 2887987 TI - Private treatment for drug dependence: GMC ban upheld by Privy Council. PMID- 2887988 TI - [Immunologic tumor markers]. PMID- 2887989 TI - [Life-prolonging effect of surgical therapy of gastrointestinal neoplasms]. PMID- 2887990 TI - [Development of the life-diminishing effect of bronchial, breast and stomach cancer 1967 to 1982 in Saarland]. PMID- 2887991 TI - [Diagnosis of pheochromocytoma]. PMID- 2887992 TI - [Long-term prognosis of Crohn disease]. PMID- 2887994 TI - [Internal medicine oncology and life insurance medicine]. PMID- 2887993 TI - [Special preventive health measures at the work site]. PMID- 2887995 TI - Behavioral suppression following 3,4-methylenenedioxymethamphetamine. AB - Rotation in rats was employed as an assay of the central dopaminergic activity of 3,4-methylenedioxymethamphetamine (MDMA). This agent was observed to possess predominantly amphetamine-like actions at low doses. However, at higher doses it also appears to stimulate the dopamine receptor directly. Following a third dose of MDMA, a significant decrease in rotation was evident to this drug and to amphetamine, suggesting a neurotoxic or long-term suppressive action of MDMA. PMID- 2887996 TI - The effects of general anaesthetics on GABAergic synaptic transmission. PMID- 2887997 TI - Neuroleptic-induced oral movements in rats: methodological issues. AB - In three separate experiments groups of rats were chronically administered neuroleptics in a variety of ways (chronic injections, subcutaneous implants, and decanoate injections) and examined for oral movements (OMs) in two different tests: in an open cage using a human observer, or in a plexiglas tube enclosure, where OMs were monitored both by a human observer and computerized video analysis system. These two testing methods showed different effects of neuroleptic administration. In the open cage, OMs tended to be enhanced during chronic neuroleptic exposure and to rapidly subside upon drug withdrawal. The enhanced OMs were especially present just after drug injections, when activity levels were low. In the observation tube environment, however, OMs tended to be low soon after drug treatments, and elevated upon withdrawal. Thus, the type of behavioral test used determines how neuroleptic-induced increases in oral activity should be interpreted. PMID- 2887998 TI - Gamma-hydroxybutyrate, a possible neurotransmitter. PMID- 2888000 TI - Contributions to medicine from bioavailability studies. PMID- 2887999 TI - Modification of certain pharmacological effects of ethanol by lipophilic alpha-1 adrenergic agonists. AB - The influence of four centrally-acting alpha-1 adrenoceptor agonists, namely, 2(2 chloro-5-trifluoromethylphenylimino) imidazolidine (St 587), cirazoline, (-) 1,2,3,4-tetrahydro-8-methoxy-5-methylthio-2-naphthalenamine ((-)SKF 89748A) and 2 (2-methylindazol-4-imino)imidazolidine (Sgd 101/75) on the pharmacological effects of ethanol was investigated. All four drugs reduced the duration of ethanol-induced hypnosis in C57B1/6 mice, this effect being proportional to their relative potencies to exert central alpha-1 agonism. In prazosin-pretreated mice, St 587 failed to reduce the hypnotic effect of ethanol, which provided strong evidence for the role of alpha-1 agonism for the hypnosis reducing effect of St 587. Hyperactivity induced in C57B1/6 mice by a subhypnotic dose of ethanol and St 587 was reported earlier. In the present study, St 587, cirazoline and (-)SKF 89748A produced similar response, but no correlation between this effect and ethanol hypnosis blockade could be established. Interestingly, this hyperactivity response was not exhibited by Swiss-Webster, BALB/c or DBA-2 mice--strains in which St 587 exerted little or no antagonism to ethanol-induced hypnosis. Of the alpha-1 agonists, only St 587 reduced the ethanol-induced hypothermia in C57B1/6 mice. St 587 also blocked this effect of ethanol in BALB/c mice in which this drug failed to reduce the ethanol-induced hypnosis. It was concluded that ethanol induced hypothermia and hypnosis are not interrelated. None of the alpha-1 agonists modified the pentobarbitone-induced hypnosis or the rate of elimination of ethanol in C57B1/6 mice. In this strain, the reduction of the duration of ethanol-induced hypnosis by the alpha-1 agonists is a selective and centrally mediated response. PMID- 2888001 TI - Adult T-cell lymphoma: case report. PMID- 2888002 TI - Gamma-glutamyl transferase: applications in forensic pathology: I: Study of blood serum recovered from human bodies. PMID- 2888003 TI - [Serum prolactin levels in chronic schizophrenics]. PMID- 2888004 TI - [Multi-indicators in the biochemical and clinical evaluation of exposure of workers in the petrochemical industry. I. Preliminary epidemiologic screening studies]. AB - Eleven non-routine biochemical and clinical indicators (selected of 26 preliminarily estimated) in Petrochemical Plant workers and in controls, localized in an increasing distance from the Plant (3-18-40 km), have been measured. Even in the 3 km distance, no effects of the Petrochemical Plant have been found. All the exposed groups exhibited changes in enzymes GGT and TA. We estimate these indicators as universal. The concentration of haptoglobin (Hp) changed in 3 groups, whereas sialic acid and arginase--in 2 exposed groups. PMID- 2888005 TI - Molecular genetics of hemophilia A in man (factor VIII deficiency). PMID- 2888007 TI - Health law and ethics. PMID- 2888006 TI - Patterns of haemagglutinating activity of Escherichia coli. AB - MR and MS adhesins on 169 strains of Escherichia coli subjected to different cultural conditions were detected. Haemagglutination Test (static settling test in plastic microtiter trays) was used and several species of red blood cells were employed. The results confirm that different media can influence the expression of the adhesins and that using as many species of red blood cells as possible one can detect different adhesins. PMID- 2888008 TI - Successful peripheral blood stem-cell autograft with a near-critical dose of myeloid progenitor cells in acute non-lymphoblastic leukaemia in relapse. AB - Rapid, complete and sustained haemopoietic reconstitution was achieved in a 69 year-old man with acute non-lymphoblastic leukaemia in relapse who received an autograft of peripheral blood cells that were collected during very early remission. The patient received 1.7 X 10(8) nucleated cells/kg bodyweight containing 63 X 10(4) myeloid progenitor cells (CFU-GM)/kg bodyweight. Trilineage engraftment was evident in the bone marrow seven days after the graft. Normal neutrophil and platelet counts were attained by day 17, on which day the patient was discharged from hospital. He remained in complete remission three months after the graft with normal blood counts and bone-marrow cellularity. The rapid and sustained haemopoietic activity in this patient, in conjunction with our previous experience of four other patients who received autografts with peripheral blood stem cells, supports the concept we have proposed that a minimum CFU-GM dose of 50 X 10(4)/kg bodyweight produces complete and sustained engraftment. The rapid recovery minimizes aplasia-related risks and suggests that such autografting can be carried out safely in first remission even in older patients. This technique should be considered as a new therapeutic option for patients with acute non-lymphoblastic leukaemia. PMID- 2888009 TI - Treatment of acute drug abuse reactions. PMID- 2888010 TI - The development of a new antihistamine: astemizole. AB - As compared with reference antihistamines, the action of astemizole is characterized by several unusual properties: highly pronounced and very specific histamine H1 antagonism, long duration of action and absence of central and sedative effects. PMID- 2888011 TI - Bronchodilator therapy in obstructive lung disease. AB - In recent years the management of patients with obstructive lung disease has been greatly simplified by the introduction of highly selective long-acting beta adrenergic agonists, slow release theophylline preparations and locally active anticholinergic agents. The beta adrenergic compounds are the most potent and many feel that they should be the first line therapy for acute episodes of airway obstruction. Methylxanthines continue to be used effectively in chronic disease and the improved bloodlevel time profiles of theophylline that are now available from sustained-release formulations provide better control of symptoms with fewer side effects than was previously possible. The new anticholinergic compounds currently undergoing testing show great promise in selected clinical situations. PMID- 2888012 TI - Pharmacotherapy of nasal disease. AB - Rhinitis may be classified as infectious (purulent), seasonal allergic, perennial allergic, perennial nonallergic (vasomotor) and nasal polyps. Pharmacotherapy can be local or systemic. A variety of compounds are available, including alpha adrenergic agonists, mast cell stabilizing agents, Beta-2 agonists, antihistamines, cholinergic antagonists and corticosteroids. In terms of histamine receptors, H1 receptors predominate in the epithelium and glands but both H1 and H2 receptors are present in nasal blood vessels. Trigeminus-reflex mediated nasal secretions, can be treated by parasympatholytic drugs. PMID- 2888013 TI - Cell fractionation, detergent sensitivity and solubilization of Dictyostelium adenylate cyclase and guanylate cyclase. AB - Cell fractionation studies have been performed, in order to obtain insight into the subcellular distribution of Dictyostelium adenylate cyclase and guanylate cyclase and also to provide a starting point for further study and isolation of these enzymes and their regulatory components. Adenylate cyclase and cAMP receptors were found in the same membrane fractions, but were distributed different from the plasma membrane marker alkaline phosphatase. Guanylate cyclase was partially soluble, partially particulate. In isopycnic gradients, particulate guanylate cyclase was present in other fractions than cAMP receptors and adenylate cyclase, but in similar ones to alkaline phosphatase. These observations are consistent with the hypothesis that cell-surface cAMP receptors and adenylate cyclase interact via a membrane-bound G-protein, whereas the receptors activate guanylate cyclase via a cytosolic factor. The adenylate cyclase activity in membranes obtained by sucrose gradient centrifugation was retained in the presence of various detergents, while with the same detergents the activity of particulate guanylate cyclase was lost. This adenylate cyclase was solubilized as assessed by gel filtration and centrifugation experiments, and it behaved heterogeneous in fractionation studies. In gel filtration, the major component eluted at a position corresponding to a Stokes radius of 4-7 nm. A purification of about 70-fold as compared to the cell homogenate was obtained by affinity chromatography of adenylate cyclase on ATP-Sepharose. We conclude that cell fractionation provides useful starting material for isolation and further study of Dictyostelium adenylate cyclase. PMID- 2888015 TI - Identification and molecular weight of SP1 synthesized from mRNA of human placenta in a wheat germ cell-free system. AB - Poly (A+)-mRNA obtained from human term placenta using guanidine HCl and oligo (dT) cellulose chromatography was translated in a wheat germ cell-free system. SDS-polyacrylamide gel electrophoresis analysis of the translation products revealed the presence of several polypeptides with molecular weights ranging from 10 KD to 70 KD. A single protein band representing around 1% of the total radioactive proteins synthesized in the presence of 2.5 micrograms of mRNA was isolated by immunoprecipitation, using specific antiserum against either the native 'Pregnancy-specific beta 1-glycoprotein' or a reduced and carboxymethylated derivative. The molecular weight of 31-2 KD of this translation product corresponding to the nonprocessed precursor could account for the 43 KD value assigned to the protein purified form human pregnant serum. PMID- 2888014 TI - Microdissection and microcloning of the long arm of human chromosome 7. AB - DNA-fragments from the region of the long arm of human chromosome 7 to which the CF-locus has been mapped recently were isolated by microdissection and microcloning. We developed a new fixation procedure resulting in inserts of 1.0 7.0 kb in length with a mean value of 2.9 kb. Regional mapping of three clones on 7q was carried out by the use of different hybrid cell lines containing fragments of human chromosome 7. PMID- 2888016 TI - Entamoeba histolytica: cloning and characterization of actin cDNA. AB - In order to study gene expression in the human parasite Entamoeba histolytica, a cDNA library of E. histolytica strain 200:NIH was constructed using the phage vector lambda gt10. Three cDNA clones (A, B and C) were selected for further analysis. Each of the three clones hybridized to a distinct mRNA. Two of these mRNAs were translated in vitro after hybrid selection, and yielded distinct translation products. One of these mRNAs, selected by hybridization to clone A, encodes the most abundantly expressed protein in E. histolytica. DNA sequence analysis of this cDNA clone identified the DNA as that encoding actin. The deduced amino acid sequence of E. histolytica actin resembles both cytoplasmic and muscle actins and has an unusual N-terminal glycine residue. We have shown that a family of actin genes is present in E. histolytica. Six different E. histolytica actin clones were obtained from a lambda gt10 genomic library using subcloned cDNA probes. Southern analysis of three different E. histolytica strains (200:NIH, Rhaman, and HM-1:IMSS) revealed at least four different actin genes. Strain HM-1:IMSS, however, differs by the presence of an additional actin gene. PMID- 2888017 TI - Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. AB - We conducted a multicenter randomized, double-blind, placebo-controlled trial of early short-term, high-dose methylprednisolone sodium succinate in 223 patients with clinical signs of systemic sepsis and a normal sensorium (112 received glucocorticoid and 111 placebo). Patients also received antibiotics and intravenous fluids. Glucocorticoid or placebo was administered intravenously by a bolus (30 mg per kilogram of body weight over 15 minutes) followed by infusion of 5 mg per kilogram per hour for nine hours. The average time between the diagnosis of sepsis and infusion was 2.8 hours. The principal end point was 14-day mortality, which was similar in the placebo (22 percent) and glucocorticoid (21 percent) groups (P = 0.97). Mortality was also not significantly different between those receiving placebo and those receiving glucocorticoid in subgroups with evidence of sepsis (21 vs. 19 percent), gram-negative bacteremia (27 vs. 7 percent), gram-positive bacteremia (18 vs. 26 percent), or all gram-negative infections (25 vs. 17 percent). Resolution of secondary infection within 14 days was significantly higher in patients receiving placebo (12 of 23) than in those receiving glucocorticoid (3 of 16) (P = 0.03), but mortality rates were similar in both treatment groups for those with unresolved infection (36 vs. 31 percent). We conclude that early high-dose glucocorticoid therapy does not reduce mortality significantly in patients with systemic sepsis who have a normal sensorium, and therefore should not be used as adjunctive therapy. PMID- 2888018 TI - Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction. AB - In a double-blind trial of streptokinase for acute myocardial infarction, 219 consecutive patients presenting with infarction within four hours (mean, 3.0 +/- 0.8) of the onset of chest pain were randomly assigned to treatment with streptokinase (1.5 million units) or placebo, given intravenously over 30 minutes. The primary end point of the study was left ventricular function in patients with first infarctions. Patients who could undergo beta-blockade also received intravenous propranolol. Heparin (for 48 hours) and a combination of low dose aspirin and dipyridamole were administered to both groups until cineangiography was performed at three weeks. In the patients with first infarctions treated with streptokinase, the left ventricular ejection fraction was 6 percentage points higher (streptokinase vs. placebo, 59 +/- 10.5 vs. 53 +/- 13.5 percent; P less than 0.005), with benefit to patients with either anterior infarction (57 +/- 11.9 vs. 49 +/- 15.9 percent; P less than 0.05) or inferior infarction (60 +/- 9.1 vs. 55 +/- 11.3 percent; P less than 0.05). Left ventricular function was improved regardless of whether concomitant propranolol was given. Survival (at 30 days) was improved with streptokinase: 2 deaths occurred among 79 patients who received this drug, as compared with 12 deaths among 93 patients who received placebo (2.5 vs. 12.9 percent, P = 0.012). Rates of reinfarction (streptokinase vs. placebo, 3 vs. 1 percent) and requirements for surgery or angioplasty (7 vs. 5 percent) were similar in the two groups. We conclude that administration of intravenous streptokinase (1.5 million units) to patients with a first myocardial infarction results in improved left ventricular function and short-term survival. PMID- 2888019 TI - Preventing hemorrhage from esophageal varices. PMID- 2888020 TI - The genetic defect in familial Alzheimer's disease is not tightly linked to the amyloid beta-protein gene. AB - Amyloid beta-protein (AP) is a peptide of relative molecular mass (Mr) 42,000 found in the senile plaques, cerebrovascular amyloid deposits, and neurofibrillary tangles of patients with Alzheimer's disease and Down's syndrome (trisomy 21). Recent molecular genetic evidence has indicated that AP is encoded as part of a larger protein by a gene on chromosome 21 (refs 5-7). The defect in the inherited autosomal dominant form of Alzheimer's disease, familial Alzheimer's disease (FAD), has been mapped to the same approximate region of chromosome 21 by genetic linkage to anonymous DNA markers, raising the possibility that this gene product, which could be important in the pathogenesis of Alzheimer's disease, is also the site of the inherited defect in FAD (ref. 5). We have determined the pattern of segregation of the AP gene in FAD pedigrees using restriction fragment length polymorphisms. The detection of several recombination events with FAD suggests that the AP gene is not the site of the inherited defect underlying this disorder. PMID- 2888021 TI - Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22. AB - Bilateral acoustic neurofibromatosis (BANF) is a severe autosomal dominant disorder involving development of multiple tumours of the nervous system including meningiomas, gliomas, neurofibromas and particularly bilateral acoustic neuromas. We have used genetic linkage analysis with DNA markers to establish that the defective gene causing BANF is on chromosome 22, and is therefore distinct from the gene for the von Recklinghausen form of neurofibromatosis, which maps to chromosome 17. Linked DNA markers will be particularly valuable in BANF, facilitating early detection of tumours and thereby permitting more effective surgical intervention. In view of the reported loss of genes on chromosome 22 in meningiomas and acoustic neuromas, the genetic localization of the primary BANF defect strongly supports the concept that the disease locus encodes a 'tumour suppressor' gene. Isolation of this gene should provide insights into the pathogenesis of acoustic neuromas and other nervous system tumours, as well as into the control of proliferation and differentiation of neural crest cells. PMID- 2888022 TI - Conformational mutations in human mitochondrial DNA. AB - Variation in the human mitochondrial DNA (mtDNA) sequence has been extensively analysed using restriction fragment length polymorphisms (RFLPs). MtDNA RFLPs have previously been attributed to nucleotide changes within restriction endonuclease recognition sites or to small insertion-deletion mutations. We now report that RFLPs detected by polyacrylamide gel electrophoresis can also result from single nucleotide substitutions which alter the mobility of small- to medium sized restriction fragments that incorporate the sequence. We have defined the mutation responsible at two loci and have identified several possible additional loci. When screening human mtDNAs with multiple restriction endonucleases, such mutations can be misidentified as insertion-deletion mutations or counted as multiple polymorphic restriction sites. This can lead to errors in constructing restriction maps and estimating sequence diversity. PMID- 2888023 TI - B-HT 920, B-HT 933, and B-HT 958: presynaptic effects on electrically evoked 3H noradrenaline release from slices of rat brain cortex and hypothalamus. AB - The effects of the three azepine compounds, B-HT 920 (6-allyl-2-amino-5,6,7,8 tetrahydro-4H-thiazolo-[4,5-d]azepine), B-HT 933 [2-amino-6-ethyl-5,6,7,8 tetrahydro-4H-oxazolo[4,5-d]azepine; azepexole] and B-HT 958 (2-amino-6-(p-chloro benzyl)-4H-5,6,7,8-tetrahydrothiazolo[5,4-d]a zepine) on electrically evoked overflow of 3H-noradrenaline were studied. Slices from parietal cortex (Cx) or nucleus anterior hypothalami (nah) were incubated with 3H-noradrenaline, superfused at 23 degrees C or 37 degrees C in the presence of the noradrenaline uptake inhibitor desipramine (3 mumol/l) and field stimulated at frequencies of 0.3 or 3 Hz. At 37 degrees C/0.3 Hz, B-HT 920 and B-HT 933 concentration dependently decreased the evoked overflow of tritium in both regions studied, whereas B-HT 958 had no effect. In a second set of experiments each drug was tested under three additional experimental conditions, i.e. 37 degrees C/3 Hz, 23 degrees C/0.3 Hz and 23 degrees C/3 Hz. Increasing the stimulation frequency to 3 Hz or lowering the superfusion temperature to 23 degrees C reduced the effects of B-HT 920 (1 mumol/l) and B-HT 933 (10 mumol/l) as compared to the effects at 37 degrees C/0.3 Hz. When tested at 23 degrees C/3 Hz, both drugs did not significantly affect the evoked overflow of tritium in the Cx or the nah. In contrast, B-HT 958 (10 mumol/l), caused a facilitation of evoked overflow in both regions when the higher stimulation frequency or the lower superfusion temperature was used. Its release-enhancing action was most pronounced at 23 degrees C/3 Hz.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888024 TI - Effects of dopamine receptor antagonists on gastrin and vomiting responses to apomorphine. AB - Apomorphine (0.05 mg/kg intravenously) was given to conscious dogs, and gastrin levels were measured in peripheral venous blood with a radioimmunoassay. Apomorphine induced an increase of gastrin levels which peaked at 5 min. The peripheral dopamine D-2/DA2 receptor antagonist domperidone (0.2 mg/kg), but not halopemide (0.1-1 mg/kg) nor the D-1/DA1 receptor antagonist SCH 23,390 (0.1 mg/kg), blocked the gastrin response to apomorphine. Both domperidone and halopemide, but not SCH 23,390, blocked the apomorphine-induced vomiting. These results suggest that apomorphine increases gastrin levels by an action at D-2/DA2 receptors, which are situated outside the blood brain barrier and differ from the receptor inducing the vomiting. PMID- 2888025 TI - The membrane potential of vascular smooth muscle appears to modulate uptake2 of 3H-isoprenaline. AB - Segments of the rabbit main pulmonary artery and of its two branches were exposed for 10 min to 50 nmol/l 3H-(+/-)-isoprenaline, and the accumulation of tritium in the tissue was determined; COMT was inhibited in all experiments. 1. The accumulation of the tritium label was sensitive to 3-O-methyl-isoprenaline (OMI), showing that this vascular smooth muscle possesses uptake2. 2. In the presence of 0.01 to 1 mumol/l (-)-noradrenaline, the accumulation of tritium was depressed (in a concentration-dependent manner). This decline involved the OMI-sensitive accumulation of 3H-isoprenaline. 3. The presence of any one of three selective alpha 1-adrenoceptor antagonists (1 mumol/l prazosin, 1 mumol/l WB4101, 10 mumol/l corynanthine) prevented the effect of 1 mumol/l (-)-noradrenaline on the accumulation of tritium. However, in the absence of (-)-noradrenaline, the three antagonists failed to affect the accumulation of tritium. 4. 10 mumol/l nicorandil caused the accumulation of tritium to increase. 5. As stimulation of alpha 1-adrenoceptors is known to result in depolarization, and as nicorandil is known to hyperpolarize this smooth muscle, it is concluded that the resting membrane potential modulates uptake2. PMID- 2888026 TI - Agonist binding at alpha 2-adrenoceptors of human platelets using 3H-UK-14,304: regulation by Gpp(NH)p and cations. AB - The agonist/alpha 2-adrenoceptor interactions at human platelet membranes have been examined in radioligand binding studies with the full agonist ligand 3H-UK 14,304 [5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline] and the antagonist ligand 3H-yohimbine. From association kinetics of different concentrations of 3H-UK 14,304 (0.75-8.1 nmol/l) a KD-value of 2.37 nmol/l in agreement with the high affinity KD-value (KDH = 1.60 +/- 0.15 nmol/l) obtained from equilibrium binding studies was derived. In the presence of Gpp(NH)p about 6% of specific radioligand binding was observed in the association reaction. Addition of Gpp(NH)p at equilibrium resulted in a rapid loss (t 1/2 less than 1 min) of approximately 80% of bound radioligand. Dissociation after addition of an excess of phentolamine (10 mumol/l) showed a biphasic time course independent of the radioligand concentration with the proportions of 1/5 of rapidly (t 1/2 less than 2 min) and 4/5 of slowly dissociating ligand (k-1 = 0.033 +/- 0.004 min-1). Application of a sequential binding model resulted in KD-values from this approach also in agreement with KDH from equilibrium binding studies. The rank order of potency for different agonists and antagonists to compete for binding with 3H-UK-14,304 indicated an alpha 2-adrenoceptor interaction: (-)adrenaline greater than or equal to clonidine greater than (-)noradrenaline greater than (-)isoprenaline and yohimbine = rauwolscine greater than phentolamine greater than prazosin greater than or equal to corynanthine greater than timolol respectively. The analysis of competition isotherms of UK-14,304 versus 3H-yohimbine (Hill-coefficient = 0.59 +/- 0.03) showed that the agonist binds to two affinity states of the alpha 2 adrenoceptor, with high (KDH = 1.77 +/- 0.50 nmol/l) and low affinity (KDL = 71.2 +/- 11.6 nmol/l) respectively. From these experiments a fraction of 56.9% +/- 2.1% of the total number of alpha 2-adrenoceptors (Bmax = 198.4 +/- 8.0 fmol/mg of protein) in the high-affinity state was calculated. Similar results were obtained from 3H-UK-14,304 saturation isotherms according to a two-state binding model (KDH = 1.60 +/- 0.15 nmol/l; KDL = 66.2 +/- 10.7 nmol/l; BmaxH = 57.6% +/- 2.3%). Adrenoceptor agonists competed for specific binding of 3H-UK-14,304 and 3H yohimbine in a manner that suggests that the 3H-UK-14,304 (approximately 3.5 nmol/l) labeled sites represent predominantly the agonist induced or stabilized high-affinity state of the alpha 2-adrenoceptor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2888028 TI - Reduction with age in the relaxation to beta-adrenoceptor agonists and other vasodilators in rat aorta. AB - We have examined the relaxation produced by the beta-adrenoceptor agonists isoprenaline and procaterol, and by sodium nitroprusside, forskolin and isobutylmethylxanthine in KCl (40 mmol/l)-contracted aortae from 6 week, 3 month and 6 month old Sprague-Dawley rats. The maximum relaxation to all agents was greatest in aortae from 6 week old animals. The relaxation to the beta adrenoceptor agonists was virtually abolished, and the relaxation to the other agents significantly reduced, in aortae from 3 and 6 month old animals. There were no significant differences in the response to any agent between aortae from 3 and 6 month old animals, so that the changes seen occurred in maturation from 6 week to 3 month. The reduced vasodilator response does not occur at the level of the beta-adrenoceptor or adenylate cyclase, since the response to sodium nitroprusside was also affected, but is a general reduction in the ability of the aorta to relax. PMID- 2888027 TI - Novel anxiolytics discriminate between postsynaptic serotonin receptors mediating different physiological responses on single neurons of the rat hippocampus. AB - The effects of buspirone on hippocampal pyramidal cells of the CA1 region were examined by means of intracellular recordings in in vitro hippocampal brain slices. Bath administration of buspirone elicited a long lasting hyperpolarization which was mediated by an increase in potassium conductance and resembled the hyperpolarizing component of the response to 5-HT (5 hydroxytryptamine). Buspirone, however, failed to mimic the depolarizing action of 5-HT or to reduce the calcium-activated after hyperpolarization. Quantitative comparisons of the hyperpolarizing responses of 5-HT and buspirone revealed that the maximal hyperpolarization induced by buspirone was significantly smaller than that induced by 5-HT. Since the buspirone induced hyperpolarization was also accompanied by a surmountable antagonism of 5-HT responses, these results indicate that buspirone behaves as a partial agonist at a subpopulation of 5-HT receptors in the CA1 region of the hippocampus. Administration of the buspirone congeners gepirone and isapirone also elicited a hyperpolarization and reduced 5 HT responses, although they lack antidopaminergic activity, indicating that the effects observed with buspirone are unlikely to be mediated through dopamine receptors. These results indicated that novel anxiolytics can discriminate between functional 5-HT receptors. In conjunction with previous biochemical and electrophysiological studies, the present results suggest that their administration might alter the balance of serotonergic actions on postsynaptic neurons. PMID- 2888029 TI - Presence of opioid receptors in mesencephalic nucleus dorsalis raphe concerned in cardiovascular regulation in cats. AB - The effects of microinjection of opioid receptor agonist and antagonist into mesencephalic nucleus dorsalis raphe, were studied on mean arterial pressure and heart rate to elucidate the nature and role of these opioid receptors in cardiovascular regulation. Microinjection of morphine (5 micrograms and 10 micrograms) into nucleus dorsalis raphe elicited both inhibitory and excitatory cardiovascular responses respectively, while microinjection of opioid receptor antagonist, naloxone (10 micrograms) failed to produce any significant cardiovascular responses. However, local pretreatment with naloxone blocked both inhibitory and excitatory responses of graded doses of morphine. These opioid receptors seem to be localised in the neurons of the nucleus since microinjection of morphine into neural structures adjoining nucleus dorsalis raphe failed to induce any cardiovascular responses. Furthermore, the dose or morphine (2 micrograms) which was ineffective when microinjected into nucleus dorsalis raphe, produced inhibitory cardiovascular responses after pretreatment with LM5008, a 5 HT uptake blocker. Similarly, the excitatory cardiovascular responses of morphine microinjection were blocked by spinal cord transection (C1) and p-CPA, guanethidine and piperoxan pretreatments, while bilateral cervical vagotomy failed to do so. Thus, it is likely that the inhibitory cardiovascular responses of morphine are mediated directly through stimulation of opioid receptors present in the neurons of nucleus dorsalis raphe while the excitatory responses to higher dose of morphine, appear to be due to a release of noradrenaline which in turn modulates the activity of neurons by acting on alpha adrenoceptors. PMID- 2888030 TI - Receptors mediating the increase in vascular permeability to kinins: comparative studies in rat, guinea-pig and rabbit. AB - The effect of bradykinin (BK) and a variety of kinin analogues and modified kinin fragments were assessed in several models representing the vascular permeability aspect of the inflammatory response. The rank order of potency of various kinin analogues to increase paw volume and skin vascular permeability in rats was sigma cyclo-(Lys1-Gly6)-BK = sigma-cyclo-kallidin much greater than BK greater than kallidin = methionyl-lysyl-BK much greater than des-Arg9-BK. The same order was seen for skin responses in day 21, rheumatoid-arthritic rats. Mepyramine, 10 mg X kg-1 almost completely inhibited rat skin vascular responses to histamine, had no effect on BK and produced a small but significant inhibition of the responses to both cyclic-kinins. A different rank order of potency for the kinins was produced in both the guinea-pig and rabbit skin; this being kallidin greater than methionyl-lysyl-BK greater than BK much much greater than sigma-cyclo-(Lys1-Gly6) BK = sigma-cyclo-kallidin greater than des-Arg9-BK. Neither of the cyclic kinins antagonised BK-induced increases in skin vascular permeability in guinea-pig or rabbit. Two modified kinin fragments, D-Pro-Phe-Arg-paranitroaniline and D-Pro Phe-Arg-heptylamide, which have previously been demonstrated to be putative B2 receptor antagonists on in vitro tissues, enhanced the effect of BK in rat skin and when injected alone produced dose-related increases in skin vascular permeability in normal and rheumatoid-arthritic rats both having approximately half the potency of BK.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888031 TI - General and strain-specific age changes at mouse limb neuromuscular junctions. AB - Age changes at limb neuromuscular junctions (NMJs) of CB57 and BALB/C mice were investigated and compared with previous results in a hybrid strain, in order to identify common characteristics of neuromuscular transmission and to assess the prevalence of signs of denervation and disuse. Resting membrane potential decreased with age in soleus muscles with no change in passive membrane properties. Miniature end-plate potential, amplitude and quantal content were greatly increased, with no change in muscle fiber diameter or nerve terminal morphometry. The various observed patterns of age changes were not those of disuse or denervation. Although there were diverse age changes in spontaneous transmitter release in different mouse strains, increased transmitter release per unit length of nerve terminal in limb muscle was a notably consistent finding across strains. It is apparently less subject to epigenetic variation during aging than most other reported neuromuscular physiological parameters. PMID- 2888033 TI - Non-uniform changes in nerve-terminal calcium homeostasis during aging. AB - Currently unpublished studies indicate reduced rates of calcium clearance from the transmitter release sites in presynaptic terminals of some, but not all, motor nerves in aged rats. Further evidence indicates that deficits in calcium regulation may not necessarily underlie observed age-related changes in evoked transmitter release. PMID- 2888032 TI - Calcium dependent aspects of synaptic plasticity, excitatory amino acid neurotransmission, brain aging and schizophrenia: a unifying hypothesis. AB - (1) The functional and structural reorganization of dendritic spines by calcium activated proteases is postulated to play a causal role in the production of the phenomenology of brain aging and in particular in the development of pathology and degeneration. Excitatory neurotransmission appears to be essential for the development of irreversible synaptic changes. (2) One of the genes modified in schizophrenia is postulated to be directly or indirectly linked to the control of excitatory neurotransmission; possibly the normal switching on of the expression of the adult form of the NMDA receptor is altered, resulting in an inappropriate functioning of this receptor. This genetic characteristic might explain the apparent resistance of schizophrenic brains to aging. PMID- 2888034 TI - Aging: effect on ex-vivo benzodiazepine binding after a diazepam injection. AB - Ex vivo [3H]flunitrazepam receptor occupation was determined in the brain of young, mature and old male Fischer 344 rats after a single intravenous injection of a low dose of diazepam. The two benzodiazepine receptor subtypes or conformations (BZ1 and BZ2) were differentiated by the displacement of [3H]flunitrazepam specific binding with the triazolopyridazine, CL 218,872. The acute diazepam injection decreased ex vivo [3H]flunitrazepam binding in only the senescent rats. The [3H]flunitrazepam binding at both the BZ1 and BZ2 receptor or receptor conformation was significantly reduced in the old rats. PMID- 2888035 TI - Growth hormone secretion after hypothalamic periventricular lesions in the rat. AB - The present study was undertaken to determine the role of the hypothalamic periventricular (PV) region in the regulation of the secretory pattern of growth hormone (GH) in adult male rats. The PV regions were destroyed stereotaxically by means of a modified Halasz's knife which was lowered through the midline and rotated several times at the level of the region. In sham-operated controls, the knife was lowered to the same region but no rotation was performed. Serial blood samplings were performed at 10-min intervals for 10 h (10.00-20.00 h), via an intracardiac cannula, at 2, 4 and 6 weeks postoperatively. In 7 sham-operated controls, GH was secreted with a surge period of about 3.5 h, with peak levels of 120-170 ng/ml whole blood and basal levels of about 10 ng/ml whole blood. In 11 PV-lesioned animals, the basal levels of GH were unaltered but the surge period decreased to about 3.0 h and peak levels increased to about twice as high as in sham-operated controls. Somatostatin concentrations in the median eminence of PV lesioned rats were significantly decreased to about 32% of that of sham-operated rats. The results suggest that, via somatostatin neurons, the PV region plays an inhibitory role in the regulation of periodicity and peak levels of GH secretory bursts. PMID- 2888036 TI - Assessment of corticotropin-releasing factor, vasopressin and somatostatin secretion by fetal hypothalamic neurons in culture. AB - The concomitant release of corticotropin-releasing factor (CRF), vasopressin (AVP) and somatostatin (SRIF) has been followed from primary cultures of rat hypothalamic neurons. 18-day-old fetal rat hypothalami were dissociated enzymatically and mechanically, then plated and maintained in a serum-containing medium at a density of 2.5 x 10(6) cells per dish (equivalent to 3 hypothalami). Cultured neurons remained viable for up to 6 weeks, and peptide release was followed by immuno-assay between days 14 and 39 in culture. The incubation media were concentrated on C4 and C8 silica columns to facilitate detection of CRF and AVP. Peptide release was measured at various times up to 4 h, at which point it was still increasing. To optimise measurements, taking into account peptide degradation, a 1-hour incubation period was chosen for further studies. Release of CRF, AVP and SRIF by 56 mM K+ or 10 microM veratridine was statistically significantly greater than basal (p less than 0.01) and was Ca2-dependent. For CRF and AVP, stimulated release increased considerably with the age of culture, whereas SRIF release was steadier. Basal release for all 3 peptides did not fluctuate greatly over this period. Basal and stimulated release of the peptides continued over at least 5 successive 1-hour periods. At day 35 of culture, the peptide content was still increasing in a pattern which paralleled the increasing content in hypothalami freshly removed from age-matched rats. In conclusion, we have demonstrated a development of CRF, AVP and SRIF production by neurons over extended periods in culture as assessed by their peptide content and increasing responses to depolarizing stimuli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888037 TI - Growth hormone responsiveness in vivo and in vitro to growth hormone releasing factor in the spontaneously diabetic BB Wistar rat. AB - In order to determine whether there is an abnormality in the pituitary responsiveness to GRF in the diabetic rat, we examined the in vivo and in vitro effects of hGRF-44 NH2 (hGRF) on growth hormone (GH) release in the spontaneously diabetic BB Wistar rat. Under pentobarbital anesthesia, hGRF was injected intravenously at a dose of 500 ng/kg in male diabetic BB Wistar rats (n = 11) and in male control Wistar rats matched for weight (n = 11). Basal serum GH concentrations were significantly lower in the diabetic group, (123 +/- 5 ng/ml, mean +/- SEM) than in the control group (362 +/- 15 ng/ml). However, the GH response to hGRF was significantly greater in the diabetic group (GH increment 873 +/- 153 ng/ml) than in the control group (268 +/- 91 ng/ml). The effect of hGRF was further tested in a perifusion system of freshly dispersed anterior pituitary cells of diabetic BB Wistar rats and control Wistar rats. Basal secretion rate of GH from cells of diabetic rats (0.85 +/- 0.06 microgram/2 pituitaries X 2 min) was lower than that from cells of control rats (1.60 +/- 0.18 micrograms/2 pituitaries X 2 min). The GH response to 2-min pulses of hGRF at concentrations of 1.56, 6.25, and 25 pM with and without somatostatin 10(-9) M was significantly greater in the diabetic group than in the control group. In conclusion, there is in the spontaneously diabetic rat an increased in vivo and in vitro GH responsiveness to exogenous hGRF suggesting an abnormality of GH regulation at the pituitary level. PMID- 2888038 TI - Effects of apomorphine and (+/-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine, injected into the striatum, on the caudate spindle in the rat. AB - The caudate spindle in rats was observed following bilateral application of apomorphine (1.5-50 micrograms) and (+/-)-3-(3-hydroxyphenyl)-N-n propylpiperidine (3-PPP, 0.3-3 micrograms) into the striatum. The smallest dose (1.5 micrograms) of apomorphine enhanced the spindle whereas with a larger dose (50 micrograms), suppression occurred. The preferential dopamine (DA) autoreceptor (inhibitory-receptor) agonist, (+/-)-3-PPP, enhanced the spindle, in a dose-dependent manner. The enhancing effect of apomorphine (1.5 micrograms) and (+/-)-3-PPP (3 micrograms) was prevented by neuroleptics, such as haloperidol (20 micrograms/kg, i.v.) and sulpiride (2 mg/kg, i.v.) at doses which, per se, did not affect the spindle. Small doses of neuroleptics are thought to block DA autoreceptors, suggesting that the enhancing effects of the DA agonists are mediated by autoreceptors. These results lend further support to the assumption that the development of the caudate spindle involves activation or DA receptors. Enhancement of the spindle, induced by injections of apomorphine into the striatum (small dose) and (+/-)-3-PPP, may be mediated by DA autoreceptors (inhibitory-receptors) located at presynaptic elements of the nigro-striatal DA system, while suppression may be due to stimulation of the postsynaptic DA receptors. PMID- 2888039 TI - Presynaptic and postsynaptic effects of histamine and histamine agonists in the superior cervical ganglion of the rat. AB - Extracellular and intracellular recording techniques were used to study the effects of histamine and the histamine agonists [impromidine (IMP) and 2 thiazolylethylamine (2-TH)] on synaptic transmission in the superior cervical ganglion of the rat in vitro. At the concentrations employed (up to 10(-5) M) these compounds did not produce detectable effects on the electrical properties of the postsynaptic neurons. Histamine produced a dose-dependent reduction in the amplitude of the extracellularly-recorded presynaptic and postsynaptic compound action potential. The H2 receptor agonist impromidine reduced only the postganglionic compound action potential. Cimetidine, a specific H2 receptor antagonist, produced parallel shifts in the log dose-response curves for impromidine. Impromidine also reduced the average size of the evoked excitatory postsynaptic potential. The reduction of the mean amplitude of the excitatory postsynaptic potential was due to a decrease in the amount of acetylcholine (ACh) liberated by each preganglionic volley (mean quantal content, m) and a diminution in quantal size. The H1 receptor agonist, 2-TH produced a dose-dependent increase in the presynaptic and postsynaptic compound action potential and in m. The increase in m was not associated with changes in quantal size. The H1 antagonists, pyrilamine and promethazine, did not prevent facilitation of ganglionic transmission induced by 2-TH. It is concluded that histamine H1 and H2 receptors exist on preganglionic axons, or terminals in sympathetic ganglia of the rat. Activation of H1 receptors facilitates release of ACh whereas H2 receptor activation results in depressed release. PMID- 2888040 TI - Blockade of excitatory amino acid receptors protects anoxic hippocampal slices. AB - Experiments in a variety of preparations have indicated that excessive activation of receptors for the excitatory amino acids glutamate and aspartate may mediate irreversible anoxic neuronal injury. We investigated this hypothesis in the in vitro hippocampal slice. Rat hippocampal slices perfused for 40 min with buffer equilibrated with 95% nitrogen/5% carbon dioxide lost their extracellular CA1 population spikes and failed to recover after prolonged reoxygeneration. It was impossible to locate cells with normal physiological properties in these anoxic slices with standard intracellular recording techniques. However, when excitatory transmission was blocked during anoxia with either high concentrations of magnesium or antagonists of excitatory amino acids (kynurenate or aminophosphonovalerate), the population spike returned to preanoxia levels. Intracellular recording showed that neurons in these protected slices had normal resting potentials, action potentials, and input resistances. These experiments provide additional support for the involvement of excitatory amino acids and their receptors in anoxic neuronal injury. PMID- 2888041 TI - The cytoskeletons of isolated, neuronal growth cones. AB - We have examined by electron microscopy the cytoskeletons of growth cones isolated from neonatal rat forebrain by the method of Gordon-Weeks and Lockerbie [Gordon-Weeks and Lockerbie (1984) Neuroscience 13, 119-136]. When fixed in suspension with conventional fixatives, isolated growth cones contain a central region filled with a branching system of smooth endoplasmic reticulum and a cortical region immediately beneath the plasma membrane that is relatively free of organelles and is composed of an amorphous granular cytoplasm. The filopodia of isolated growth cones are also devoid of organelles and contain a cytoplasm that is similar in appearance to that in the cortical region. No microtubules or neurofilaments have been found in these growth cones. When isolated growth cones were prepared for electron microscopy by a method which preserves actin filaments [Boyles, Anderson and Hutcherson (1985) J. Histochem. Cytochem. 33, 1116-1128], microfilaments were found throughout the cortical cytoplasm. In the filopodia, the microfilaments were bundled together and oriented longitudinally. Filopodial microfilament bundles often extended into the body of the growth cone and could traverse it completely. Inclusion of Triton X-100 (1% v/v) in the fixative solubilized the membranes and soluble cytoplasmic proteins of growth cones, allowing an unobscured view of the microfilament cytoskeleton including the core bundle of microfilaments in filopodia. Suspended within the cytoskeleton were the coats of coated vesicles. These were particularly numerous at the broad bases of filopodia. Microfilaments bound heavy meromyosin and were cytochalasin B (2.0 X 10(-7) M) sensitive. Individual microfilaments branched and within filopodia they were extensively cross-linked by thin (7 nm) filaments. Microtubules and neurofilaments were not seen in these cytoskeletons despite the fact that the fixative contained a Ca2+ chelator. When growth cones were preincubated in taxol (14 microM) their cytoskeletons were found to contain microtubules. These were located mainly in the centre of the growth cone, were absent from the filopodia and were contiguous with microfilaments. We conclude that the cytoskeletons of isolated neuronal growth cones from neurones of the central nervous system are mainly composed of actin microfilaments. Although microtubules are not normally present, there is a pool of soluble tubulin which will form microtubules in the presence of taxol. This may imply that those microtubule-associated proteins that promote tubulin polymerization are absent in the growth cone or are below the concentration threshold for polymerization. PMID- 2888042 TI - Characterization of an N-methyl-D-aspartate receptor component of synaptic transmission in rat hippocampal slices. AB - The involvement of N-methyl-D-aspartate receptors in synaptic transmission from Schaffer collateral-commissural fibres to CA1 neurons has been investigated in rat hippocampal slices. When the perfusion medium was changed from one containing 1 mM Mg2+ to one with no added Mg2+ there was a pronounced increase in the amplitude of the population spike, the appearance of secondary population spikes and in some slices spontaneous epileptiform discharges developed. The secondary and spontaneous population spikes were abolished by the selective N-methyl-D aspartate antagonist, D-2-amino-5-phosphonovalerate. The effects on the primary population spike depended on the strength of synaptic activation. At low intensities, the N-methyl-D-aspartate antagonist reduced or abolished this response whereas at high intensities the primary population spike was slightly increased in amplitude by this compound. Mg2+ had dose-dependent (20-500 microM) effects on synaptic responses which were identical to those of D-2-amino-5 phosphonovalerate. Increasing the Ca2+ concentration over a range of 1-3 mM also reduced or abolished secondary population spikes and, at low stimulus intensities, the primary population spike. At higher stimulus intensities, however, the primary population spike was insensitive to the Ca2+ concentration over this range. These results demonstrate the major extent to which N-methyl-D aspartate receptors can contribute to synaptic transmission and epileptiform activity in the CA1 region of the hippocampus. They also show that an important role of Mg2+ in this region is to prevent significant activation of this receptor system during low-frequency synaptic transmission. PMID- 2888044 TI - Major localization of aminopeptidase M in rat brain microvessels. AB - The localization of two enkephalin-hydrolysing aminopeptidases i.e. aminopeptidase M (aminopeptidase N, EC 3.4.11.2) relatively insensitive to puromycin (Ki = 78 microM), and a puromycin-sensitive aminopeptidase (Ki = 1 microM) was studied in rat brain. The two aminopeptidases were differentially identified and/or localized using polyclonal anti-aminopeptidase M antibodies displaying anticatalytic activity and the inhibitors puromycin, bestatin and amastatin. Microvessels represent a major localization of cerebral aminopeptidase M as shown by the intense immunostaining of their walls in sections from various regions as well as in a fraction isolated from cerebral cortex homogenates by a sieving procedure. As compared to the starting homogenate, aminopeptidase M activity was enriched about twenty fold in this microvascular fraction. Aminopeptidase M was identified in this fraction by comparing the inhibitory potencies of antibodies and peptidase inhibitors towards the hydrolysis of [tyrosyl-3,5-3H, Met5]enkephalin to those found for the purified enzyme. A rather high aminopeptidase M activity was also localized in choroid plexuses. Following differential and gradient centrifugation analysis of cerebral cortex homogenates, aminopeptidase M activity was also enriched (by five to six fold) in fractions containing synaptic membranes. No significant soluble aminopeptidase M activity could be detected. These data suggest a dual localization of cerebral aminopeptidase M in microvessels and synaptic membranes consistent with its roles in preventing the access of circulating peptides to brain as well as in inactivating neuropeptides released from cerebral neurones. In comparison, puromycin-sensitive aminopeptidase activity, which is about 100 fold higher than aminopeptidase M activity in brain, was relatively low in microvessels and non detectable in fractions enriched in synaptic membranes, being almost entirely restricted to soluble fractions. PMID- 2888043 TI - Redistribution of transmitter amino acids in rat hippocampus and cerebellum during seizures induced by L-allylglycine and bicuculline: an immunocytochemical study with antisera against conjugated GABA, glutamate and aspartate. AB - The effects of the convulsants L-allylglycine and bicuculline on the distribution of gamma-amino-butyric acid (GABA), glutamate and aspartate in rat brains were assessed immunocytochemically, using antisera raised against glutaraldehyde protein conjugates of the respective amino acids. In accord with previous biochemical studies of GABA content, L-allylglycine treatment was followed by a decreased immunoreactivity for GABA in the hippocampus and cerebellum, whereas treatment with bicuculline led to an increased immunoreactivity in the hippocampus, but not in the cerebellum. Different cells and zones were affected differentially. With both convulsants the hippocampus showed the most pronounced changes in the neuropil of the pyramidal and granular cell layers. L-Allylglycine treatment led to a substantial decrease in the concentration of detectable GABA immunoreactive bouton-like dots in the stratum oriens, radiatum and lacunosum moleculare and in the deep hilar region, but did not produce statistically significant changes in this parameter in the outer and intermediate zones of the dentate molecular layer. In the cerebellum, the decrease in GABA immunoreactivity after L-allylglycine treatment was less in the basket cell terminals than in other GABA-containing elements. Neither convulsant altered the average staining intensity for aspartate or glutamate in the two regions studied, but L allylglycine reduced the level of aspartate-like immunoreactivity in hippocampal hilar cells. All the changes described were evident after 20 min of seizure activity and were qualitatively similar after 60 min of seizure (animals paralysed and ventilated). Our results indicate that L-allylglycine or bicuculline given intravenously exerts specific effects on cerebral amino acid metabolism. The nature and magnitude of these effects show inter-regional variations and also differ among cellular compartments within each region. Amino acid immunocytochemistry may prove to be a valuable tool for the investigation of metabolic changes associated with epileptic seizures and should be particularly useful in regions showing heterogeneous changes that would tend to cancel each other in biochemical analyses. PMID- 2888045 TI - Phelorphan, an inhibitor of enzymes involved in the biodegradation of enkephalins, affected the withdrawal symptoms in chronic morphine-dependent rats. AB - Intracerebroventricular administration of phelorphan (158 nmol/2 microliters), a blocker of dipeptidylaminopeptidase (enkephalinase B) and other enzymes involved in the enkephalin biodegradation, inhibited in chronic morphine-dependent rats, the occurrence of some of the naloxone-precipitated withdrawal symptoms. This effect of phelorphan was compared with an equimolar dose of the dipeptidyl carboxypeptidase inhibitor (enkephalinase A), thiorphan. The results indicate that both drugs decrease some of the naloxone-precipitated withdrawal symptoms (writhing, digging, head hiding, chewing, diarrhoea and Straub tail), while others were potentiated (penile licking) or unaltered (wet dog shakes, grooming and rearing). In addition, phelorphan compared with the controls or thiorphan, pretreated animals, increased the frequency of paw tremor, head shakes, scratching, erection and ejaculation, but other symptoms were decreased (stretching) or unaltered (teeth chattering). The results are discussed in light of the differences in permeability and specificity of the two enkephalinase inhibitors. Furthermore, these data support the hypothesis that the use of enkephalinase inhibitors might be a promising way for the attenuation of the severity of the withdrawal syndrome. PMID- 2888046 TI - Protective effect of antihistamines on cerebral oedema induced by experimental pneumothorax in newborn piglets. AB - As a consequence of general hypoxaemia evoked experimentally by bilateral pneumothorax, brain oedema of vasogenic type developed in newborn piglets after 4 h survival. Histamine receptor antagonists, mepyramine (H1-receptor blocker), metiamide, cimetidine and ranitidine (H2-receptor antagonists) were administered either intraperitoneally or intrathecally to check to what extent the formation of brain oedema could be reduced. Mepyramine and ranitidine decreased the accumulation of water, sodium and albumin in the parietal cortex. By measuring the concentration of histamine, the presence of a histamine pool was demonstrated in the cerebral microvessels. The results suggest that histamine, if released upon hypoxic injury from the microvascular store, can take an important part in the development of vasogenic brain oedema. PMID- 2888047 TI - Dendritic morphology of indoleamine cells revealed by intracellular injection of lucifer yellow in fixed carp retina. AB - The dendritic morphology of indoleamine amacrine cells in carp retina was investigated by identifying their fluorescent cell bodies by preloading with noradrenaline followed by iontophoretic injection of Lucifer Yellow in isolated and aldehyde-fixed preparations under microscopic control. Although two subpopulations of serotonin-like immunoreactive amacrine cells (small and large in soma size) were found, small cells were not seen in aldehyde-fixed preparations. Cells preloaded with noradrenaline corresponded to large immunoreactive cells and were labeled with Lucifer Yellow. The cell bodies labeled were located at the innermost level of the inner nuclear layer, and gave rise to three to five primary dendrites which branched frequently and were found mainly in sublamina a of the inner plexiform layer. These cells examined in an intermediate region between the optic disc and the retinal periphery were pyriform in soma shape while dendritic fields were found or oval covering an area of 0.18 +/- 0.05 mm2 (510 +/- 80 microns in diameter). Cell density in this region was about 32 cells/mm2 and, therefore, their dendritic field coverage was approximately 6.0. PMID- 2888049 TI - Acetylcholine permits long-term enhancement of neuronal responsiveness in cat primary somatosensory cortex. AB - Acetylcholine (ACh) was administered iontophoretically to single neurons in cat somatosensory cortex. Using extracellular recording techniques, neuronal responsiveness was determined at regular intervals from the number of action potentials produced either by iontophoretically applied glutamate or by tactile stimulation of the cutaneous receptive field. The responses were altered in only 21% (13/61) of the neurons following the application of ACh alone. In contrast, 75% (66/88) of the neurons displayed altered responses during administration of ACh simultaneously with either iontophoretically administered glutamate or with tactile stimulation of the receptive field. Forty-seven percent (29/62) of the responses potentiated in the presence of ACh remained enhanced for periods lasting from 8 min to over 1 h. The responsiveness of cortical neurons to afferent inputs changes during the reorganization of somatotopic maps that occurs after deafferentation, and perhaps during some forms of learning. As ACh has been implicated in some of these processes, it may be that the changes in responsiveness observed here following iontophoretically applied ACh are similar to those which facilitate the acquisition of neuronal responses to altered or novel afferent inputs. PMID- 2888048 TI - Somatostatin 28 and neuropeptide Y innervation in the septal area and related cortical and subcortical structures of the human brain. Distribution, relationships and evidence for differential coexistence. AB - Somatostatin 28- and neuropeptide Y-containing innervations were mapped in the human medial forebrain (eight control brains) with immunohistochemistry, using the sensitive avidin-biotin-peroxidase method. Peptidergic perikarya and fibers had an extensive distribution: they were densest in the ventral striatum (nucleus accumbens, olfactory tubercle and bed nucleus of the stria terminalis) and infralimbic cortex, of intermediate density in the medial septal area and of lowest density in the dorsal and caudal lateral septal nucleus. Somatostatin-like immunoreactive perikarya and fibers were generally more numerous than the neuropeptide Y-like immunoreactive ones, but more faintly labeled. Their pattern of distribution was strikingly similar in some of the limbic structures studied but clearly distinct in others. Excellent overlap of neuropeptide Y and somatostatin-like immunoreactivity was detected in: (1) the medial septal area, where innervation occasionally formed perivascular clusters; (2) the nucleus accumbens and olfactory tubercle, characterized by dense patchy innervation; and (3) the laterodorsal septal nucleus, scarcely innervated. In the latter structures, most peptidergic neurons were double-labeled. On the other hand, both peptidergic innervations clearly differed in the lateroventral septal nucleus and the bed nucleus of the stria terminalis which contained distinct clusters of somatostatin-like immunoreactive neurons devoid of neuropeptide Y-like immunoreactivity. Also, the perineuronal and peridendritic axonal plexuses ('woolly fibers') present in these structures were only labeled with somatostatin. In the infralimbic cortex, the relation between the peptides varied according to the cortical laminae. Coexistence of somatostatin and neuropeptide Y frequently occurred in layer VI and in the subcortical white matter, whereas layer V and particularly layers II and III contained a contingent of neurons labeled only with somatostatin. Dense horizontal terminal networks in layers I and VI however were similar for both peptides. These findings support the existence of two different types of somatostatin-like immunoreactive perikarya as regards colocalization with neuropeptide Y. Their particular topographical segregation within the cortical and subcortical structures analysed suggest that they could have different connections and functional properties.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2888050 TI - Facilitated induction of hippocampal long-term potentiation in slices perfused with low concentrations of magnesium. AB - The generation of long-term potentiation of synaptic transmission in area CA1 of hippocampal slices of the guinea-pig has been examined in solutions containing low concentrations of magnesium ions. It was found that the induction of long term potentiation is greatly facilitated in slices perfused with 0.1 mM magnesium but much less so with 0.5 mM magnesium solution. The long-term potentiation evoked by brief tetanization in 0.1 mM magnesium was prevented following application of the N-methyl-D-aspartate receptor antagonist 2-amino-5 phosphonovalerate. Moreover, the response to tetanization, recorded in the dendritic layer, contained a much greater than normal component blocked by 2 amino-5-phosphonovalerate. The latter represents current through postsynaptic N methyl-D-aspartate receptor channels, suggesting that the facilitation of long term potentiation is related to a facilitated opening of these channels. The results support the notion that the generation of long-term potentiation is related to current through N-methyl-D-aspartate receptor channels which is under the control of extracellular magnesium ions. PMID- 2888051 TI - Reduced somatostatin-like immunoreactivity in cerebral cortex in nonfamilial dysphasic dementia. AB - A nonfamilial syndrome is described in two middle-aged men who presented with progressive aphasia without incipient signs of cognitive impairment. In each case, 2 years elapsed before progressive functional decline or behavioral disabilities supervened. Radiologic studies documented asymmetric left cerebral atrophy that was progressive. The structure of the language disintegration was distinctive and not like that in Alzheimer's disease. Pathologic studies performed at postmortem examination of one patient documented asymmetric cerebral atrophy with nonspecific histopathologic changes. Biochemical studies revealed normal tissue levels of choline acetyltransferase activity, but reduced somatostatin-like immunoreactivity. Since cerebral somatostatin is largely present in intrinsic cortical neurons, while cholinergic innervation is largely derived from the basal forebrain, these findings suggest that nonfamilial dysphasic dementia may be an example of a distinct class of dementia due to intrinsic cortical degeneration, with sparing of the basal forebrain. PMID- 2888052 TI - Carrier assessment for mothers and sisters of isolated Duchenne dystrophy cases: the importance of serum enzyme determinations. AB - DNA studies (restriction fragment length polymorphism linkage analysis and deletion analysis with pERT87) and serum creatine kinase/pyruvate kinase (CK/PK) measurements were done to determine the carrier status of 59 mothers and sisters of isolated Duchenne dystrophy (DD) cases. The results of DNA studies modified the carrier risks for 34 of the 59 (58%), but the derived risks often did not differ importantly from risks calculated by conventional methods. Elevated CK/PK provided strong evidence of the carrier state for 24 of the 59 (41%), and CK/PK frequently provided data unavailable through DNA studies. Serum enzyme determinations remain an important means of evaluating DD carrier suspects and are especially valuable in isolated-case families. Enzyme testing should be combined with DNA studies to achieve the best estimate of carrier risk. PMID- 2888053 TI - [Ibopamine, adrenolytic drugs and renal function]. PMID- 2888054 TI - [Our experience in the treatment of gastric hemorrhage]. PMID- 2888055 TI - [Premedication for endoscopic examinations with intravenous administration of chlordesmethyldiazepam. A controlled double-blind study with diazepam and placebo]. PMID- 2888057 TI - Diagnosis of renal proximal tubular injury by urinary immunoassay for a proximal tubular antigen, the adenosine deaminase binding protein. AB - A sandwich ELISA assay has been formatted from two commercially available murine monoclonal antibodies, URO-4 and URO-4a, directed against a 120,000 dalton glycoprotein, the adenosine deaminase binding protein (ABP), found on the brush border of the renal proximal tubular epithelial cell. Untimed urine samples from 37 normal individuals and urinary ABP less than 0.1 AU; 37 patients with pure glomerular disease had ABP less than 0.4 AU (with 29, or 76% less than 0.2 AU); 10 patients with pre-renal azotaemia had ABP less than 0.6 (with 8, or 80% less than 0.3 AU). In contrast, 79 patients with post-ischaemic acute tubular necrosis had ABP greater than 0.6 AU. Acute renal failure due to myoglobinuria, contrast dye, and aminoglycoside toxicity were all associated with urinary ABP greater than 1.0 AU. In addition, all six patients with acute bacteraemic pyelonephritis had ABP greater than 0.7 AU, as opposed to ABP less than 0.2 AU in the urines of 12 women with acute cystitis. We conclude that this monoclonal antibody based urinary assay is a sensitive measure of renal proximal tubular injury, reliably distinguishes acute tubular from glomerular disease, and may be helpful in differentiating forms of urinary tract infection. PMID- 2888056 TI - [Multicenter study on the effectiveness and tolerance of a bromazepam + propantheline combination in patients with irritable bowel syndrome]. PMID- 2888058 TI - Effects of ketamine on the in vivo toxicity of quinolinate and N-methyl-D aspartate in the rat hippocampus. AB - Systemic injections of ketamine (30 mg/kg, i.p.) decreased the neurotoxicity of the NMDA agonists NMDA (N-methyl-D-aspartic acid) and quinolinic acid injected into the hippocampus of the rat, although such protection was incomplete. Simultaneous injections of ketamine into the hippocampus decreased rather than increased these protective effects. In contrast, almost complete protection was provided by intra-hippocampal injections of DL-2-amino-5-phosphonovaleric acid (DL-APV). The duration of anaesthesia was not responsible for the protective effects of systemic ketamine, as the intracerebral injections of the NMDA agonists produced similar neuronal lesions under both halothane or nembutal anaesthesia. PMID- 2888059 TI - Non-competitive regulation of phencyclidine/sigma-receptors by the N-methyl-D aspartate receptor antagonist D-(-)-2-amino-5-phosphonovaleric acid. AB - D-(-)-2-Amino-5-phosphonovaleric acid (D(-)AP5), a selective, potent competitive antagonist of N-methyl-D-aspartate (NMDA)-type excitatory amino acid receptors was used to investigate the relationship between NMDA receptors and phencyclidine (PCP) binding. Incubation of rat brain membranes with D(-)AP5 decreased the apparent number of PCP/sigma-receptors in dose-dependent fashion without affecting their affinity for [2-thienyl-3H]cyclohexylpiperidine (TCP). These data, taken together with electrophysiological evidence that PCP non competitively antagonizes NMDA receptor-mediated transmission, are consistent with the hypothesis that the PCP/sigma-receptor may be situated in or near a channel regulated by an NMDA receptor complex. PMID- 2888060 TI - Chronic treatment with classical and atypical antipsychotic drugs differentially decreases dopamine release in striatum and nucleus accumbens in vivo. AB - In vivo electrochemical techniques were employed to demonstrate that repeated treatment with classical antipsychotic drugs reduced basal dopamine (DA) release in the striatum and nucleus accumbens, whereas repeated treatment with atypical antipsychotics decreased DA release only in accumbens. Administration of apomorphine temporarily reversed these decreases to values comparable to those measured in vehicle-treated controls. These results suggest that the delayed onset of antipsychotic efficacy and extrapyramidal side effects involve a decrease in DA release in mesolimbic and nigrostriatal DA terminal fields, respectively. The results further suggest that induction of depolarization block in DA neurons may be the mechanism underlying these effects. PMID- 2888061 TI - Innervation of facial skin but not masticatory muscles or the tongue by trigeminal primary afferents containing somatostatin in the rat. AB - Using retrograde transport of a fluorescent dye, True blue, the peripheral tissues innervated by trigeminal ganglion neurones containing somatostatin have been investigated. Of ganglion neurones retrogradely labelled from injections of dye into the facial skin, 3.45% were found to be immunoreactive for somatostatin. In contrast, none of the neurones labelled from injections of dye into the tongue or masseter muscle were found to contain this peptide. This demonstration of a restricted distribution of somatostatin-containing primary afferents raises the possibility that somatostatin may be involved in functions which are specific to skin and not to the other tissues examined. PMID- 2888062 TI - Extracellular overflow of glutamate, aspartate, GABA and taurine in the cortex and basal ganglia of fetal lambs during hypoxia-ischemia. AB - Extracellular levels of excitatory and inhibitory amino acids were measured in the cortex and striatum of asphyxiated fetal lambs. The fetus was exteriorized from the anesthetized ewe and dialysis probes were placed in the parietal cortex and caudate nucleus. Cerebral blood flow was measured with Xe-clearance. Cortical somatosensory-evoked potentials and electroencephalogram (EEG) were continuously recorded. Asphyxia was induced by clamping the umbilical cord or by graded compression of the maternal aorta. Asphyxia accompanied by elevated cerebral blood flow resulted in a moderate rise in extracellular amino acid levels. During extreme asphyxia, i.e. abolished evoked potentials and reduced cerebral blood flow, marked extracellular elevations of glutamate (3- to 11-fold), aspartate (3- to 7-fold), gamma-aminobutyric acid (GABA) (3- to 5-fold) and taurine (3- to 18 fold) occurred, the higher values representing striatum. Excessive levels of excitatory amino acids may exert injurious effects on immature neurons during such hypoxic-ischemic states. PMID- 2888063 TI - Involvement of N-methyl-D-aspartate receptors in the augmenting response in rat neocortex. AB - The augmenting response was elicited in the neocortex of anaesthetized rats by 10 Hz stimulation of thalamic nuclei. The N-methyl-aspartate (NMA) antagonists 2 amino-5-phosphonopentanoate or 2-amino-7-phosphonoheptanoate were applied topically to the exposed cortex by replacement of fluid in a small plastic cylinder lying on the pial surface. The antagonists delayed the development of augmentation and hastened its decline. It is suggested that this may indicate the involvement of NMA receptors in the augmenting phenomenon in cortex. PMID- 2888064 TI - Inhibition of N-methyl-D-aspartate-induced hippocampal [3H]norepinephrine release by phencyclidine is dependent on potassium concentration. AB - This study examined the ability of phencyclidine (PCP) to inhibit the responses to N-methyl-D-aspartate (NMDA) in depolarizing concentrations of K+. The effects of PCP and Mg2+ on NMDA-induced norepinephrine release from hippocampal slices were measured during superfusion with various extracellular concentrations of K+. The IC50 values for Mg2+ and PCP were significantly higher in K+ concentrations above 6 mM. These data are supportive of the hypothesis that PCP produces a voltage-dependent blockade of NMDA-activated ion channels. PMID- 2888065 TI - Cerebral GABA-ergic and glutamatergic function in hepatic encephalopathy. AB - Measurement of amino acids in brain tissue obtained at autopsy from cirrhotic patients dying in hepatic coma revealed a threefold increase in glutamine and a concomitant decrease in brain glutamate. The GABA levels were found to be unaltered. Studies using an animal model of portal-systemic encephalopathy gave similar results. Glutamic acid decarboxylase (GAD) activities were within normal limits, both in the brains of cirrhotic patients and portocaval-shunted rats. A previous study reported normal [3H]GABA binding to synaptic membrane preparations from cerebral cortex in these animals. Taken together, these findings suggest that cerebral GABA function is not impaired in hepatic encephalopathy associated with chronic liver disease and portal-systemic shunting. On the other hand, there is evidence to suggest that the releasable pool of glutamate may be depleted in brain in hepatic encephalopathy. Data consistent with this hypothesis include: Reduction in the evoked release of endogenous glutamate by superfusion of hippocampal slices with pathophysiological levels of ammonia; ammonia-induced reduction of glutamatergic neurotransmission; and an increase in the number of [3H]glutamate binding sites in synaptic membrane preparations from hyperammonemia rats and from rats with portocaval shunts. Such neurochemical changes may be of pathophysiological significance in hepatic encephalopathy. PMID- 2888066 TI - Cerebral ammonia metabolism in normal and hyperammonemic rats. AB - Brain ammonia is generated from many enzymatic reactions, including glutaminase, glutamate dehydrogenase, and the purine nucleotide cycle. In contrast, the brain possesses only one major enzyme for the removal of exogenous ammonia, i.e., glutamine synthetase. Thus, following administration of [13N]ammonia to rats [via either the carotid artery or cerebrospinal fluid (csf)], most metabolized label was in glutamine (amide) and little was in glutamate (plus aspartate). Since blood-and csf-borne ammonia are converted to glutamine largely, if not entirely, in the astrocytes, it is not possible from these types of experiments to predict with certainty the metabolic fate of the bulk of endogenously produced ammonia. By comparing the specific activity of L-[13N]glutamate to that of L-[amine 13N]glutamine following intracarotid [13N]ammonia administration it was concluded that metabolic compartmentation is no longer intact in the brains of rats treated with the glutamine synthetase inhibitor L-methionine-SR-sulfoximine (MSO) and that blood and brain ammonia pools mix in such animals. In MSO-treated animals, recovery of label in brain was low (approximately 20% of controls), and of the label remaining, a prominent portion was in glutamine (amide) (despite an 87% decrease in brain glutamine synthetase activity). These data are consistent with the hypothesis that glutamine synthetase is the major enzyme for metabolism of endogenously--as well as exogenously--produced ammonia. The rate of turnover of blood-derived ammonia to glutamine in normal rat brain is extremely rapid (t1/2 less than or equal to 3 s), but is slowed in the brains of chronically (12-14-wk portacaval-shunted) or acutely (urease-treated) hyperammonemic rats (t1/2 less than or equal to 10 s). The slowed turnover rate may be caused by an increased astrocytic ammonia, decreased glutamine synthetase activity, or both. In the hyperammonemic rat brain, glutamine synthetase is still the only important enzyme for the removal of blood-borne ammonia. Hyperammonemia causes an increase in brain lactate/pyruvate ratios and decreases in brain glutamate and brainstem ATP, consistent with an interference with the malate-aspartate shuttle. In vitro, pathological levels of ammonia also inhibit brain alpha-ketoglutarate dehydrogenase complex and, less strongly, pyruvate dehydrogenase complex. The rat brain does not adapt to prolonged hyperammonemia by increasing its glutamine synthetase activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2888067 TI - Somatostatin and neuropeptide Y are unaltered in the amygdala in schizophrenia. AB - Although a biochemical abnormality has been postulated in the etiology of schizophrenia, evidence supporting this hypothesis has been conflicting. Because of the presence of somatostatin-like immunoreactivity (SLI) in limbic system nuclei of the brain, we examined postmortem concentrations of SLI in patients dying with schizophrenia and in normal controls. Concentrations of SLI in Brodmann cortical area 38, hippocampus, caudate, putamen, nucleus accumbens, and both segments of the globus pallidus were not significantly different from controls. In addition, we examined both SLI and neuropeptide-Y-like immunoreactivity (NPYLI) in subnuclei of the amygdala and the substantia innominata. There were no significant alterations in either neuropeptide as compared with controls. PMID- 2888068 TI - Aluminum-induced decreases in choline acetyltransferase, tyrosine hydroxylase, and glutamate decarboxylase in selected regions of rabbit brain. AB - The neuropathological and neurochemical effects of intracisternally administered aluminum-powder suspensions were studied in adult rabbits. The right half of each brain was fixed for neuropathological examination, and neurotransmitter synthesizing enzyme activities were measured in homogenates of structures dissected from the left half of each brain. The neuropathological changes associated with aluminum-induced encephalomyelopathy, including neurofibrillary degeneration, were observed in several regions of the central nervous system of the aluminum-treated rabbits. The striatum was consistently free of changes. Decreases in choline acetyltransferase and tyrosine hydroxylase activities of more than 30% were observed in the striatum of animals within 14-21 d and at longer times after aluminum injection. The decrease in striatal choline acetyltransferase activity appears to be unrelated to pathological changes in the striatal cholinergic neurons. The decrease in tyrosine hydroxylase activity in the striatum may be unrelated to neuropathological changes in dopaminergic cell bodies in the midbrain. Significant decreases in glutamate decarboxylase activity in the cerebellum may be related to cell losses in this region, whereas choline acetyltransferase activity deficits in the whole hippocampus remain unexplained. PMID- 2888069 TI - Genetic differences in mitochondrial ATPase. PMID- 2888070 TI - Cutaneous polyarteritis nodosa. PMID- 2888071 TI - Polyarteritis nodosa presenting with migratory soft tissue swelling. PMID- 2888072 TI - Prevention of childhood poisoning: efficacy of an educational program carried out in an emergency clinic. AB - For many inner-city families, the emergency clinic is the most frequent and sometimes the only point of contact with medical services. We hypothesized that this setting could serve as an opportunity to direct a health promotion at a population that might not receive such a message elsewhere. The objectives of the program were (1) to remind parents of the telephone number of the Massachusetts Poison Center, (2) to ensure that parents have ipecac for use in an emergency, and (3) to counsel parents on how to use ipecac. Of 403 families recruited from the emergency clinic and divided randomly into intervention and nonintervention groups, 262 families completed the follow-up interview 6 months later (65%). Results showed that 68% of intervention families compared with 42% of control families reported ipecac storage at follow-up (chi 2 = 7.65, P = .005) and that 40% of intervention families v 25% of control families reported familiarity with the use of ipecac (chi 2 = 4.04, P = .04). Accessibility to the poison center's telephone number was reported by 62% of intervention families and by 49% of control families (chi 2 = 4.60, P = .13). Finally, 42% of intervention families v 25% of control families reported that they had a sticker on their phone with the number of the poison center on it (chi 2 = 4.60, P = .03). Our results suggest that a brief intervention, even in an emergency clinic, can introduce the topic of poisoning prevention to families and can encourage the storage of syrup of ipecac in the home. PMID- 2888073 TI - Ipecac-induced emesis and reduction of plasma concentrations of drugs following accidental overdose in children. AB - Syrup of ipecac is widely used following accidental drug overdosage in children. Proof of its efficacy, however, in reducing the risk of poisoning is limited. We prospectively studied the effect of early v late induction of emesis by ipecac in 50 children younger than 5 years of age with accidental acetaminophen poisoning. The mean estimated ingested dose was 165 mg/kg, and all patients vomited within 15 to 255 (mean 78) minutes postingestion. Although the predicted four-hour plasma acetaminophen concentration was 97 +/- 4 micrograms/mL (mean +/- SEM, calculated on the basis of the estimated ingested dose), the measured four-hour plasma acetaminophen concentration was 34 +/- 5 micrograms/mL (P less than .01). To assess the efficacy of early v late ipecac-induced emesis, we used the ratio of measured to predicted four-hour acetaminophen plasma concentration. The ratio of the measured to predicted four-hour level increased as the delay in time to vomiting increased (r = .60, P less than .001). Ipecac syrup was administered more promptly when available in the home than when obtained from a pharmacy or a medical facility (26 +/- 8 v 83 +/- 13 minutes postingestion, respectively; P less than .001) and vomiting occurred earlier (49 +/- 9 v 103 +/- 12 minutes postingestion; P less than .01). Although the mean estimated doses ingested were greater in patients who received ipecac syrup at home, their four-hour plasma acetaminophen concentrations were lower. These data suggest that prompt administration of ipecac syrup results in a greater reduction in plasma acetaminophen concentrations in potentially toxic overdosages in children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888076 TI - Sequence of a human glutamine synthetase cDNA. PMID- 2888075 TI - Two novel genes, fanA and fanB, involved in the biogenesis of K99 fimbriae. AB - The nucleotide sequence of the region located transcriptionally upstream of the K99 fimbrial subunit gene (fanC) was determined. Several putative transcription signals and two open reading frames, designated fanA and fanB, became apparent. Frameshift mutations in fanA and fanB reduced K99 fimbriae expression 8-fold and 16-fold, respectively. Complementation of the mutants in trans restored the K99 expression to about 75% of the wild type level, indicating that fanA and fanB code for transacting polypeptides involved in the biogenesis of K99 fimbriae. The fanA and fanB gene products FanA and FanB were not detectable in minicell preparations, indicating that both polypeptides are synthesized in very small amounts. However, in an in vitro DNA directed translation system FanA and FanB could be identified. The deduced amino acid sequences of FanA and FanB showed that both polypeptides contain no signal peptides, indicating a cytoplasmic location. Furthermore, the polypeptides are very hydrophilic, mainly basic, and exhibit remarkable homology to each other and to a regulatory protein (papB) encoded by the pap-operon (1). Some of these features are characteristics of nucleic acid binding proteins, which suggests that FanA and FanB have a regulatory function in the synthesis of FanC and the auxiliary polypeptides FanD H. PMID- 2888074 TI - Distinct sites of action of clostridial neurotoxins revealed by double-poisoning of mouse motor nerve terminals. AB - (1) We investigated the effects of single- and double-poisoning with tetanus toxin (TeTx), botulinum neurotoxin type A (BoTx A) and botulinum neurotoxin type B (BoTx B) on spontaneous and nerve-evoked quantal transmitter release at motor endplates of the triangularis sterni preparation of the mouse. (2) Inhibitory effects of TeTx and BoTx B on spontaneous and nerve-evoked transmitter release were very similar, except that the action of BoTx B required 500-fold lower concentrations and was less dependent on temperature. BoTx A caused stronger inhibition of quantal release than TeTx or BoTx B, but was comparatively much easier counteracted by 4-aminopyridine (4-AP). (3) In contrast to BoTx A, with TeTx or BoTx B the increase of transmitter release following onset of 50 Hz nerve stimulation was delayed for a few seconds and synaptic latencies of quanta showed large variations. This release pattern was also evident in all double-poisoning experiments, regardless of intoxication sequence. (4) Inhibition of evoked release was found to be slightly stronger with TeTx than with BoTx B, so the amount of nerve-evoked quanta released after double-poisoning with any sequence of these toxins always approached that of TeTx. In no case supra-additive actions were observed. (5) A strong reduction of evoked quanta was observed when BoTx A was applied in addition to either of the two other toxins. With reversed poisoning sequences (BoTx A - TeTx or BoTx A - BoTx B) the resulting values remained at the extremely low level of BoTx A. (6) In the presence of 4-AP double poisoning with any combination between BoTx A and TeTx or BoTx B (regardless of intoxication sequence) revealed supra-additive effects, since the number of quanta released was considerably lower than that obtained with any of the toxins alone (in the presence of 4-AP). (7) Our results indicate that tetanus toxin and botulinum toxin type B have a common site of action which is different and independent from that of botulinum toxin type A. PMID- 2888077 TI - RFLPs associated with MDR2, a member of the human multidrug resistance gene family mapped to chromosome 7. PMID- 2888078 TI - Hgi AI restriction fragment length polymorphism at the human glutathione S transferase 2 locus. PMID- 2888079 TI - A PstI polymorphism for the human porphobilinogen deaminase gene (PBG). PMID- 2888080 TI - Presence of a TaqI polymorphism in the human glutamate dehydrogenase (GLUD) gene on chromosome 10. PMID- 2888081 TI - A HindIII polymorphism detected by the cDNA encoding amyloid beta protein of Alzheimer's disease. PMID- 2888082 TI - A human single-copy DNA probe (DR 47) detects a Taq I RFLP on chromosome 9 (D9S5). PMID- 2888084 TI - MspI polymorphism in the 3' flanking region of the human factor VIII gene. PMID- 2888083 TI - A moderately frequent RFLP identified by both SacI and BanII with a probe from the HOX2 locus in man (17q11-17q22). PMID- 2888085 TI - Isolation of a full-length cDNA clone encoding human tyrosine hydroxylase type 3. PMID- 2888087 TI - A frequent HaeIII RFLP of the human fibronectin gene. PMID- 2888086 TI - An RFLP associated with the human T-cell antigen receptor alpha chain locus. PMID- 2888088 TI - A new RFLP for L1.4 (D5S4) an anonymous genomic clone localised to chromosome 5. PMID- 2888089 TI - RFLP for the human lipoprotein lipase (LPL) gene: HindIII. PMID- 2888090 TI - Multiple RFLPs demonstrated for epidermal growth factor receptor (EGFR) on chromosome 7. PMID- 2888091 TI - RFLP for the glucocorticoid receptor (GRL) located at 5q11-5q13. PMID- 2888092 TI - SacI RFLP in the human von Willebrand factor gene. PMID- 2888093 TI - A new RFLP detected with the anonymous single copy genomic clone L1.7 (D5S1). PMID- 2888094 TI - An Xba I polymorphism 3' to the human erythropoietin (EPO) gene. PMID- 2888095 TI - AvaII RFLP at the human apolipoprotein CII (APO CII) gene locus. PMID- 2888096 TI - Lack of interaction between cimetidine and buspirone. AB - Simultaneous administration of cimetidine and many benzodiazepine anxiolytics has resulted in decreased body clearance and marked prolongation of the half-life of these agents. The pharmacokinetic interaction of buspirone, a new nonbenzodiazepine anxiolytic, and cimetidine was studied in 10 healthy male volunteers. Each received, in order, buspirone 45 mg/day (days 1-7), no drug (days 8-14), cimetidine 1 g/day (days 15-21), buspirone 45 mg/day plus cimetidine 1 g/day (days 22-28), and cimetidine 1 g/day (days 29-31). Buspirone and 1 pyrimidinyl piperazine (1-PP), an active metabolite, pharmacokinetics, urinary excretion of cimetidine, a manual dexterity test, the Stroop color-word interference test, and a visual analog mood scale were evaluated on each treatment. There were no significant (p greater than 0.05) differences among treatments for any measurement except for a slight (31%) but significant (p less than 0.05) increase in the 1-PP Cmax value. These results suggest that within the normal therapeutic dosage ranges for both drugs, it is unlikely that a clinically significant interaction between them will occur. PMID- 2888098 TI - Influence of centrally administered somatostatin and two related peptides on intestinal absorption of water and electrolytes in conscious dogs. AB - The effects of intracerebroventricular (ICV) administration of somatostatin (SRIF) and two related peptides, anti SRIF and SMS 201-995, on jejunal fluxes of water, Na+ and K+ were investigated in dogs prepared with a Thiry-Vella (TV) loop. Intestinal transport in the TV loop and concomitant transit time were also measured during infusion (2 mg/min) of an isotonic electrolyte solution and phenol-red bolus injections. Basal net water absorption was reduced significantly (p less than 0.01) over periods of 2 to 5 hr and in a dose-related manner, with ICV administrations of SRIF (5 to 100 ng/kg); doses of SRIF, 5 to 25 times higher but administered IV, were inactive. Similar reductions in the net fluxes of water, Na+ and K+ were observed over 2 to 5 hr following ICV administration of a putative somatostatin antagonist and SMS 201-995 at doses of 100 ng/kg. Neither metoclopramide (1 mg/kg), phentolamine (0.1 mg/kg) nor methysergide (0.2 mg/kg) given IV were able to antagonize the effects of centrally administered SRIF (100 ng/kg) on intestinal fluxes. In contrast, the effects of SRIF were abolished completely by naloxone (0.2 mg/kg) but not methyl-naloxone (0.3 mg/kg) given systemically. It is concluded that somatostatin and the two related peptides act centrally to reduce jejunal absorption of water and electrolytes. The effects of SRIF appear to be related to opiate receptors, possible involving central nerve pathways which utilize opiate-like transmitters. PMID- 2888097 TI - The effects of adrenergic, opioid and pancreatic polypeptidergic compounds on feeding and other behaviors in neonatal leghorn chicks. AB - The present study examined the effects of intracerebral (IC) administration of pancreatic polypeptide (PP), neuropeptide Y (NPY), norepinephrine (NE), dynorphin and naloxone on food intake in 2-day-old Leghorn chicks. Of the compounds studied, only PP (20 micrograms) and naloxone (10 and 20 micrograms) elevated food intake significantly as compared to saline injections. NPY, a potent orexigenic agent in mammals, did not elevate consumption significantly in a dose related fashion. This latter finding was attributed to the occurrence of tonic clonic convulsions following NPY administration. However, for those chicks which did not exhibit behavioral convulsions, food intake appeared to be elevated by 1, 5 and 10 micrograms of NPY. Similarly, NE did not elevate food intake but instead induced sedation and narcolepsy, a behavioral response which could be distinguished from the convulsions observed after NPY. In a separate group of chicks, the effect of NPY on cortical activity was examined. Bipolar electrodes were used to record EEG activity before and after IC injections of saline, NPY or NE. The behavioral convulsions induced by NPY corresponded with an increase in high amplitude sharp-wave activity, which persisted for up to 30 min post injection. Collectively, these results suggest that the neurochemical substrates for feeding in 2-day-old Leghorn chicks are distinct from those underlying food intake in adult mammals. PMID- 2888100 TI - Unexpectedly high levels of opioid peptides in rat brain membranes. AB - Several considerations led us to directly measure, using radioimmunoassay, the levels of dynorphin-A(1-8), cholecystokinin-8, and Met5-enkephalin-Arg6-Gly7-Leu8 (MERGL) in lysed-P2 membranes, membranes incubated 60 min at 25 degrees C in 50 mM TRIS-HCl at pH 7.4, and membranes preincubated 60 min at 25 degrees C in TRIS buffer containing 0.4 M NaCl. Lysed-P2 membranes contained neuropeptides at levels between 0.253 and 1.727 pmol/mg protein. Incubating membranes in buffer alone decreased membrane peptide levels by 40 to 60%. Preincubations in the presence of 0.4 M NaCl resulted in even greater reductions in the peptide content of membranes (between 58 and 90%), without changing [3H]etorphine binding. Detailed comparisons of the two binding sites labeled by [3H]naloxone revealed changes in binding parameters induced by preincubation with NaCl. Taken collectively, these studies demonstrate that lysed-P2 membranes contain sequestered peptides that are not bound to opiate receptors. PMID- 2888099 TI - Effects of a novel opioid peptide antagonist on rat bladder motility in vivo. AB - The agonist, and opioid antagonist, effects of intracerebroventricularly (ICV) given D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (CTP), a cyclic analogue of somatostatin octapeptide, were evaluated using the micturition reflex of the anesthetized rat as the endpoint. Antagonist effects were evaluated against equieffective doses of selective mu [D-Ala2,NMPhe4,Gly-ol]enkephalin (DAGO) and delta [D-Pen2,D-Pen5] enkephalin (DPDPE) opioid agonists. At low ICV doses, CTP preferentially antagonized DPDPE rather than DAGO; increasing the dose of CTP further effectively antagonized both mu and delta agonists, while even higher doses showed an agonist effect alone which was not blocked by adrenergic, cholinergic or opioid antagonists. Selective opioid antagonist doses of CTP failed to block the inhibition of the micturition reflex produced by pentobarbital. Possible residual somatostatin like properties of CTP were tested by using somatostatin as a possible antagonist of equieffective doses of DPDPE and DAGO; somatostatin did not antagonize these agonists. Repeated exposure to CTP resulted in the development of acute tolerance to the agonist effect, and also prevented the inhibition of the reflex by high doses of somatostatin, with the converse experiment showing a similar pattern; thus, repeated somatostatin resulted in tolerance and subsequent cross-tolerance to the agonist effects of CTP. In animals tolerant to somatostatin, CTP nevertheless behaved as an opioid antagonist. The present results indicate that CTP possesses opioid antagonist properties in vivo which are pharmacological in nature but nevertheless retains residual somatostatin-like activity at higher doses. PMID- 2888101 TI - The degradation of dynorphin A in brain tissue in vivo and in vitro. AB - The demonstration of analgesia following in vivo administration of dynorphin A (Dyn A) has been difficult. In contrast, a number of electrophysiological and behavioral effects reported with in vivo injection of Dyn A can be produced by des-tyrosine dynorphin A (Dyn A 2-17). This suggested the extremely rapid amino terminal degradation of dynorphin A. To test this hypothesis, we examined the degradation of dynorphin A following in vivo injection into the periaqueductal gray (PAG) as well as in vitro using rat brain membranes under receptor binding conditions. In vivo, we observed the rapid amino terminal cleavage of tyrosine to yield the relatively more stable destyrosine dynorphin A. This same cleavage after tyrosine was observed in vitro. Inhibition of this aminopeptidase activity in vitro was observed by the addition of dynorphin A 2-17 or dynorphin A 7-17 but not after the addition of dynorphin A 1-13, dynorphin A 1-8, dynorphin B or alpha neo-endorphin suggesting a specific enzyme may be responsible. The detection of the behaviorally active des-tyrosine dynorphin A following in vivo injection of dynorphin A suggests that this peptide may play an important physiological role. PMID- 2888102 TI - [Renal changes in viral hepatitis evaluated on the bases of gamma glutamyltransferase and alanyl aminopeptidase activities in the urine of patients]. PMID- 2888103 TI - Effect of infection with Eimeria tenella upon the cecal bacterial population in monoflora chickens. AB - Monoflora chickens were established at 2 days of age by an oral inoculation with one of six species of bacteria (Lactobacillus acidophilus, Bifidobacterium thermophilum, Bacteroides vulgatus, Clostridium perfringens, Escherichia coli, or Streptococcus faecalis) and were infected with Eimeria tenella (5 X 10(4) oocysts per bird) 2 days later. There were two experimental groups for each bacterium: birds infected with bacteria alone and birds infected with a combination of bacteria and E. tenella. Seven days after E. tenella infection, counts of B. thermophilum in the cecal contents were significantly lower for E. tenella infected birds than for those infected by B. thermophilum alone, whereas 10 days after E. tenella infection, counts were higher for E. tennella-infected birds. The population of L. acidophilus in the cecal contents of the E. tenella-infected chickens 10 days after inoculation was significantly greater than that in uninfected chickens. No significant differences were observed between the numbers of B. vulgatus, C. perfringens, and S. faecalis in cecal contents of groups with and without E. tenella infections. PMID- 2888104 TI - [Spontaneous bilateral perirenal hematoma as a complication of Wegener's granulomatosis]. PMID- 2888105 TI - [Treatment of external pancreatic fistula by depot somatostatin]. PMID- 2888106 TI - [Beta-blockaders in first-intention treatment of exercise angina pectoris]. AB - Effort angina may be treated with nitrates, beta-blockers or calcium antagonists which are equally effective. The choice of the appropriate treatment sometimes depends on clinical data, on the contraindications indications specific to each therapeutic class or on side-effects. In most cases, beta-blockers should be preferred since their side-effects are rare provided their contra-indications are respected, they are easy to administer and above all, they exert a protective effect on the heart demonstrated after myocardial infection and highly probable in angina. The possible occurrence, during prolonged treatment, of unstable angina or myocardial infarction--both conditions in which beta-blockers alone or combined with other drugs have been shown to be effective--is in favour of this treatment. However, the frequent presence of a vasomotor factor in the different clinical forms of coronary disease justifies the use of vasodilators concurrently with beta-blockers, notably in patients with severe angina. PMID- 2888107 TI - The relationship of borderline personality disorder to the affective disorders. AB - The proposition that Borderline Personality Disorders (BPDs) are atypical forms of affective disorder is reviewed in the light of pharmacological, outcome and clinical studies. The case can be summarized briefly as follows: that the basic underlying cause of borderline symptomatology is an effective disorder; that mood disturbance, which is viewed as primarily biological, is more important than developmental experience and life events in maintaining borderline personality features; that therapies aimed at treating the mood disorder should therefore be expected to relieve the personality disorder. However, the pharmacological studies suggest that antidepressant medications have been largely ineffective in treating well defined BPD, except in the presence of coexisting depressive disorder. Indeed low dose antipsychotics have a demonstrated efficacy in the treatment of BPD, which does not strengthen the case for an affective etiology. Follow-up studies of BPDs suggest that dramatic characterological features seen at the time of index hospitalization tend to recede by the time patients are in their 30s, that major affective disorders fail to emerge over time, and that long term marginal functioning derives from long-term maladaptive patterns across a variety of areas. Clinical studies suggest that 20-60 per cent of patients with BPD have a concomitant depressive disorder. Conversely the prevalence of personality disorders in depressions varies with depressive category, with considerably higher incidence of personality disturbance found in non-endogenous depression. The high rate of coexistence of these two disorders does not imply causality or primacy, in the sense that it is the affective disorder which brings out and causes the personality disorder. The review concludes that the assertion that BPD represents atypical affective disorder begs the possibility that it is precisely in having borderline features that they are atypical, and hence distinct. PMID- 2888108 TI - The positive-negative dimension in schizophrenia: its validity and significance. AB - It has been recently proposed that positive (productive) and negative (deficit) symptoms in schizophrenia constitute distinct syndromes that carry different etiological, prognostic, and treatment implications. Inconclusive results to date may be attributable to methodological weaknesses, including problems of measurement and lack of longitudinal, dynamic, and multiphasic investigation. We describe a series of multidimensional studies on the validity and significance of this distinction, deriving from a new rating instrument and separate typological, dimensional, longitudinal, phasic, and psychopharmacological research perspectives. The data suggest that positive and negative features represent opposing polarities of psychopathology which can be reliably assessed. Various sources of syndromal validation were demonstrated, including construct and criterion-related validity and differential response to psychotropic medication. Positive and negative syndromes were equally prevalent in the acute and chronic phases of schizophrenia but stable only in the latter. The meaning of the syndromes also varied according to chronicity. In the chronic stage, a negative profile was uniquely associated with ominous genealogical, premorbid, and phenomenological signs, whereas in acute schizophrenia it carried favorable import and predicted successful outcome. The results contest a monolithic concept of the positive-negative distinction and fail to support the prevalent hypothesis of structural organic impairment underlying the negative syndrome. We instead postulate a dual-process model that distinguishes between neuroleptic responsive arousal-related (positive) and neuroleptic resistant development (negative) components in chronic schizophrenia. PMID- 2888109 TI - Expression and secretion of type beta transforming growth factor by activated human macrophages. AB - Alveolar macrophages activated with concanavalin A and peripheral blood monocytes activated with lipopolysaccharide secrete type beta transforming growth factor (TGF-beta). There is minimal TGF-beta secretion in unactivated monocytes, even though TGF-beta mRNA is expressed in these cells at a level similar to that in activated, lipopolysaccharide-treated cultures. U937 lymphoma cells, which have monocytic characteristics, also express mRNA for TGF-beta. Freshly isolated monocytes, both control and lipopolysaccharide-treated, secrete an acid-labile binding protein that inhibits TGF-beta action. We conclude the following: (i) that expression of TGF-beta mRNA is unrelated to monocyte activation, (ii) that secretion of TGF-beta is induced by monocyte activation, and (iii) that cosecretion of TGF-beta and its monocyte/macrophage-derived binding protein may modulate growth factor action. In contrast, monocytic expression of other growth factor genes, such as the B chain of platelet-derived growth factor, is not constitutive and requires activation. PMID- 2888110 TI - Cloning of partial cDNA encoding differentiation and tumor-associated mucin glycoproteins expressed by human mammary epithelium. AB - Human mammary epithelial cells secrete and express on their cell surfaces complex mucin glycoproteins (Mr greater than 250,000) that are developmentally regulated, tumor-associated, and highly immunogenic. Studies using monoclonal antibodies directed to these glycoproteins suggest that their molecular structures can vary with differentiation stages in the normal gland and in malignancy. To analyze the molecular nature of these glycoproteins, milk mucin was affinity-purified and deglycosylated with hydrogen fluoride, yielding bands at 68 and 72 kDa on silver stained gels. Polyclonal and monoclonal antibodies to the stripped core protein were developed and used to screen a lambda gt11 expression library of cDNA made from mRNA of the mammary tumor cell line MCF-7. Seven cross-reacting clones were isolated, with inserts 0.1-1.8 kilobases long. RNA blot analysis, using as a probe the 1.8-kilobase insert subcloned in plasmid pUC8 (pMUC10), revealed transcripts of 4.7 and 6.4 kilobases in MCF-7 and T47D mammary tumor cells, whereas normal mammary epithelial cells from pooled milks have additional transcripts. The expression of mRNA correlates with antigen expression as determined by binding of two previously characterized anti-mucin monoclonal antibodies (HMFG-1 and HMFG-2) to seven cell lines. Restriction enzyme analysis detected a restriction fragment length polymorphism when human genomic DNA was digested with EcoRI or HinfI. PMID- 2888111 TI - Role of glutamic acid-181 in DNA-sequence recognition by the catabolite gene activator protein (CAP) of Escherichia coli: altered DNA-sequence-recognition properties of [Val181]CAP and [Leu181]CAP. AB - It has been proposed that Glu-181 of the catabolite gene activator protein (CAP) makes direct contact with certain base pairs of the specific DNA site. We have purified wild-type CAP and two substituted CAP variants, [Val181]CAP and [Leu181]CAP, and have assessed the DNA-sequence-recognition properties in vitro with respect to positions 5, 6, 7, 8, and 16 of the DNA site. The data indicate that [Val181]CAP and [Leu181]CAP fail to discriminate between the consensus DNA base pair and the three non-consensus-DNA base pairs at 2-fold-related positions 7 and 16 of the DNA site. In contrast, [Val181]CAP and [Leu181]CAP retain the ability to discriminate between different base pairs at positions 5 and 8 of the DNA site. We conclude that Glu-181 of CAP makes a direct contact with 2-fold related positions 7 and 16 of the DNA site, as proposed previously based on in vivo results. We propose that upon replacement of Glu-181 by valine or leucine, this contact is eliminated and is replaced by no other functional contact. We estimate that the contact by Glu-181 with each position contributes -0.7 kcal/mol to the total CAP-DNA binding free energy. PMID- 2888112 TI - Coupling of replication type histone mRNA levels to DNA synthesis requires the stem-loop sequence at the 3' end of the mRNA. AB - The role of the 3' end of mRNA in coupling between the level of histone mRNAs and DNA synthesis was examined. We introduced modified mouse histone H3 genes into mouse fibroblasts and studied the regulation of several different H3 mRNAs that are not terminated with a normal histone 3' end. In two cases, the stem-loop sequences were deleted from the mRNAs and replaced either by 3' sequences flanking the H3 gene or by globin 3' untranslated region sequences including the polyadenylylation signal. In the former case, approximately equal to 50% of the modified mRNA was polyadenylylated, whereas in the latter case all of the mRNA had a polyadenylylated terminus. In contrast to the normal histone mRNAs, these mRNAs, including the nonadenylylated form, were stable when DNA synthesis was inhibited with several drugs. The levels of two other histone mRNAs, each containing the stem-loop sequences as an internal part of the mRNA, also were stable when DNA synthesis was inhibited. These results indicate that the posttranscriptional coupling of histone mRNA levels to DNA synthesis requires the presence of the stem-loop sequences at the 3' end of the mRNA. PMID- 2888114 TI - Integration host factor is required for the DNA inversion that controls phase variation in Escherichia coli. AB - The on-and-off expression (phase variation) of type 1 fimbriae, encoded by fimA, in Escherichia coli is controlled by the inversion of a promoter-containing 314 base-pair DNA element. This element is flanked on each side by a 9-base-pair inverted, repeat sequence and requires closely linked genes for inversion. Homology analysis of the products of these genes, fimB and fimE, reveals a strong similarity with the proposed DNA binding domain of lambda integrase, which mediates site-specific recombination in the presence of integration host factor. Integration host factor, encoded by himA and hip/himD, binds to the sequence 5' TNYAANNNRTTGAT 3', where Y = pyrimidine and R = purine, in mediating integration excision. In analyzing the DNA flanking the fim 314-base-pair inversion sequence, we found the adjacent sequence 5' TTTAACTTATTGAT 3', which corresponds perfectly with the consensus integration host factor binding site. To characterize the role of himA in phase variation, we transduced either a deletion of himA or an insertionally inactivated hip/himD gene into an E. coli strain with a fimA-lacZ operon fusion. We found the rate of phase variation decreases sharply from 10(-3) to less than 10(-5) per cell per generation. Southern hybridization analysis demonstrates that the himA mutation results in a failure of the switch-generated genetic rearrangement. When the transductant was transformed with a himA+ plasmid, normal switching returned. Thus integration host factor is required for normal type 1 fimbriae phase variation in E. coli. PMID- 2888113 TI - Dissociation of bradykinin-induced prostaglandin formation from phosphatidylinositol turnover in Swiss 3T3 fibroblasts: evidence for G protein regulation of phospholipase A2. AB - In Swiss 3T3 fibroblasts bradykinin stimulated inositol phosphate (InsP) formation and prostaglandin E2 (PGE2) synthesis. The EC50 values for stimulation of PGE2 synthesis and InsP formation by bradykinin were similar, 200 pM and 275 pM, respectively. Guanosine-5'-[gamma-thio]triphosphate stimulated PGE2 synthesis and InsP formation, and guanosine-5'-[beta-thio]diphosphate inhibited both PGE2 synthesis and InsP formation stimulated by bradykinin. Neither bradykinin stimulated PGE2 synthesis nor InsP formation was sensitive to pertussis toxin. Phorbol ester, dexamethasone, and cycloheximide distinguished between bradykinin stimulated PGE2 synthesis and InsP formation. Phorbol 12-myristate 13-acetate enhanced bradykinin-stimulated PGE2 synthesis but inhibited bradykinin-stimulated InsP formation. Pretreatment of cells with dexamethasone for 24 hr inhibited bradykinin-stimulated PGE2 synthesis but was without effect on bradykinin stimulated InsP formation. Cycloheximide inhibited bradykinin-stimulated PGE2 synthesis but was without effect on bradykinin-stimulated InsP formation. When bradykinin was added to cells prelabeled with [3H]choline, the phospholipase A2 products lysophosphatidylcholine and glycerophosphocholine were generated. In cells pretreated with dexamethasone, lysophosphatidylcholine and glycerophosphocholine formation induced by bradykinin were inhibited. Treatment of cells with phorbol ester enhanced bradykinin-induced formation of these metabolites. The data suggest that bradykinin receptors are coupled by GTP binding proteins to both phospholipase C and phospholipase A2 and that phospholipase A2 is the enzyme that catalyzes release of arachidonate for prostaglandin synthesis. PMID- 2888116 TI - The Leeuwenhoek lecture, 1986. Environmental carcinogens and papillomaviruses in the pathogenesis of cancer. AB - In many areas of the world there is a geographically localized high incidence of alimentary and bladder cancer in cattle. Studies in western Scotland have demonstrated that this phenomenon is associated with ingestion of bracken fern. However, the affected animals and herds were shown also to have an unusually high infection rate of alimentary papillomas caused by a previously unrecognised bovine papillomavirus (BPV) and that these tumors could undergo malignant transformation. Long-term field and experimental studies were started and indicate that the pathogenesis of the tumours and their relationship to virus infection and food-derived mutagens is complex. Results from these studies, and from cellular and molecular biology experiments, are presented and discussed in the context of recent papillomavirus findings in the human subject. PMID- 2888115 TI - Detection of disease-specific restriction fragment length polymorphisms in pemphigus vulgaris linked to the DQw1 and DQw3 alleles of the HLA-D region. AB - Pemphigus vulgaris in Israeli Ashkenazi and non-Ashkenazi Jews and in Austrian non-Jewish patients is strongly associated with the DR4 and DRw6 alleles of the HLA-D region class II genes. Restriction fragment length polymorphism analysis was undertaken with DQ beta, DQ alpha, and DR beta cDNA probes. Hybridization with the DQ beta probe identifies Pvu II, BamHI, and EcoRV fragments that absolutely discriminate pemphigus vulgaris patients from healthy DR-, DQ-, and ethnic-matched controls. In contrast the DQ alpha and DR beta probes failed to identify disease-specific restriction fragment length polymorphism fragments. These studies indicate that DQw1 and DQw3 polymorphisms carried by pemphigus vulgaris patients may be directly involved in predisposition to the disease or may be tightly linked to the susceptibility gene itself. To our knowledge, this is the first example of an HLA restriction fragment length polymorphism that is highly associated with susceptibility to autoimmune disease. PMID- 2888117 TI - Activation of a common effector system by different brain neurotransmitter receptors in Xenopus oocytes. AB - Xenopus oocytes possess 'native' muscarinic receptors, which give rise to oscillatory chloride currents; similar responses are elicited by activation of foreign receptors to serotonin, glutamate and noradrenaline, expressed in oocytes after injection of messenger RNA from rat brain. When low concentrations of two agonists are applied together, the combined response is greater than would be expected from the sum of the responses to each agonist applied alone. Potentiation of acetylcholine by serotonin is blocked by the serotonin antagonist methysergide; conversely, the potentiation of serotonin by acetylcholine is blocked by the muscarinic antagonist atropine. This indicates that each agonist acts on a distinct receptor. The interactions between serotonin, acetylcholine and other agonists provide further evidence that the different receptors may all 'link in' to a common receptor-channel coupling system, in which phosphoinositide metabolism and calcium liberation lead to the opening of chloride channels in the oocyte membrane. PMID- 2888118 TI - Metabolism of glucose into glutamate via the hexose monophosphate shunt and its inhibition by 6-aminonicotinamide in rat brain in vivo. AB - The treatment of rats for 4 h with 6-aminonicotinamide (60 mg kg-1) resulted in an 180-fold increase in the concentration of 6-phosphogluconate in their brains; glucose increased 2.6-fold and glucose 6-phosphate, 1.7-fold. Moreover, lactate decreased by 20%, glutamate by 8% and gamma-aminobutyrate by 12%, and aspartate increased by 10%. No significant changes were found in glutamine and citrate. In blood, 6-phosphogluconate increased 5-fold; glucose, 1.4-fold and glucose 6 phosphate, 1.8-fold. The metabolism of glucose in the rat brain, via both the Embden-Meyerhof pathway and the hexose monophosphate shunt, was investigated by injecting [U-14C]glucose or [2-14C]glucose, and that via the hexose monophosphate shunt alone by injecting [3,4-14C]glucose. The total radioactive yield of amino acids in the rat brain was 5.63 mumol at 20 min after injection of [U 14C]glucose, or 5.82 mumol after injection of [2-14C]glucose; by contrast, it was 0.62 mumol after injection of [3,4-14C]glucose. The treatment of rats with 6 aminonicotinamide showed significant decreases in these values, owing to decreases in the radioactive yields of glutamate, glutamine, aspartate, gamma aminobutyrate, and alanine+glycine+serine. Glutamate isolated from the brain contained approximately 43% of its radioactivity in carbon 1 after injection of [3,4-14C]glucose, in contrast to 13% and 18% after injection of [U-14C]glucose and [2-14C]glucose, respectively, in both the control and treated rats. The calculations based on these findings showed that approximately 69% of the 14C labelled glutamate was formed from [14C]acetyl coenzyme A (acetyl CoA) and the residual 31% by 14CO2 fixation of pyruvate after injection of [3,4-14C]glucose in both control and treated rats. The results gave direct evidence that glutamate and gamma-aminobutyrate in the brain were formed by metabolism of glucose via the hexose monophosphate shunt as well as via the Embden-Meyerhof pathway. From the radioactive yields of glutamate formed via [14C]acetyl CoA it was estimated that approximately 7.8% of the total glucose utilized was channelled via the hexose monophosphate shunt. Assuming that [14C]glutamate formed by carbon-dioxide fixation of pyruvate was also dependent on the metabolism of glucose through the hexose monophosphate shunt, the estimated value was approximately 9.5% of the total glucose converted into glutamate. The results of the present investigation, taken in conjunction with other findings, suggest that the utilization of glucose via the hexose monophosphate shunt is functionally important in the rat brain. PMID- 2888120 TI - The Wellcome Foundation lecture, 1986. The molecular regulators of normal and leukaemic blood cells. AB - The development of a cell-culture system for the cloning and clonal differentiation of different types of blood cell has made it possible to identify: (i), the proteins that regulate growth and differentiation of different cell lineages in normal and leukaemic blood cells; (ii), the molecular basis of normal and abnormal control of cell development in blood-forming tissue; and (iii), how to suppress malignancy in leukaemic cells. By using myeloid blood cells as a model system, it has been shown that normal blood cells require different proteins to induce cell viability and multiplication (growth-inducers) and differentiation (differentiation-inducers), that there is a hierarchy of growth-inducers which act at various stages of cell development, and that a growth-inducer can switch on production of a differentiation-inducer. Gene cloning has established a multigene family for these proteins. Identification of these proteins and their interaction has shown how growth and differentiation are regulated in normal development and demonstrated the mechanisms that uncouple growth and differentiation so as to produce malignant cells. Normal cells require an external source of growth-inducing protein for cell viability and multiplication. Cells can become leukaemic by genetically changing this normal requirement for growth without blocking response to normal differentiation inducers. The mature cells induced by adding these normal protein-inducers are then no longer malignant. Other genetic changes which inhibit differentiation by the normal blood-cell regulatory proteins can occur in the evolution of leukaemia. But even these leukaemic cells may still be induced to differentiate by other compounds that can induce differentiation by alternative pathways. The differentiation of leukaemic to mature cells, which stops the cells from multiplying, results in the suppression of malignancy by bypassing genetic changes that produce the malignant phenotype. The activity of blood-cell growth- and differentiation-inducing proteins has been shown in culture and in the body. They can, therefore, be clinically useful to correct defects in the development of normal and leukaemic blood cells. PMID- 2888121 TI - Growth of Paracoccus denitrificans on [2,3-13C]succinate and [1,4-13C]succinate. I. The flux of carbon in energy metabolism and the operation of the TCA cycle. AB - The metabolism of Paracoccus denitrificans, grown on either [2,3-13C]succinate or [1,4-13C]succinate, was investigated by using gas chromatography-mass spectrometry. The distribution of label in a group of metabolites closely related to the TCA-cycle intermediates showed that the flux of carbon from succinate in energy metabolism in vivo was via pyruvate (malic enzyme) and acetyl CoA. The labelling pattern of the carboxyl groups showed that one fifth of the succinate pool was formed by the regeneration of succinate via the TCA cycle, and four fifths was supplied externally as substrate from the medium. PMID- 2888122 TI - Growth of Paracoccus denitrificans on [2,3-13C]succinate and [1,4-13C]succinate. II. Isoleucine biosynthesis. AB - Paracoccus denitrificans was grown on either [2,3-13C]succinate or [1,4 13C]succinate, and extracts were analysed by using gas chromatography-mass spectrometry. The distribution of label in isoleucine indicated that the 2 ketobutyrate required for isoleucine biosynthesis was mainly produced from pyruvate by 2-keto-acid chain elongation (i.e. the 'pyruvate elongation pathway'). Approximately 10% of isoleucine was produced by a second pathway involving propionyl CoA. Threonine and glutamate were not utilized by P. denitrificans as a source of 2-ketobutyrate production for isoleucine biosynthesis under the growth conditions used. PMID- 2888119 TI - The interplexiform-horizontal cell system of the fish retina: effects of dopamine, light stimulation and time in the dark. AB - Interplexiform cells contact cone horizontal cells in the fish retina and probably release dopamine at synaptic sites. The effects of dopamine, certain related compounds, and light and dark regimes were tested on the intracellularly recorded activity of horizontal cells in the superfused carp retina to elucidate the functional role of the interplexiform cell. Dopamine application onto retinae kept in the dark for 30-40 min increased the size of the responses of cone horizontal cells to small-spot stimuli but decreased response size to large- and full-field stimuli. Dopamine also altered the response waveform of these cells; the transient at response onset increased in size and the depolarizing afterpotential decreased in size. Haloperidol, a dopamine antagonist, blocked these effects of dopamine application. Forskolin, an adenylate cyclase activator, increased the size of the responses of the cells to small-spot stimuli. Superfusion of vasoactive intestinal peptide did not produce any effects on horizontal cells. The results indicate that dopamine produces multiple physiological effects on cone horizontal cells by activation of an intracellular enzyme system. We propose that some of these effects are probably related to an uncoupling of the gap junctions between horizontal cells, but that other effects are most likely not explained on this basis and reflect additional changes induced in the cells by dopamine. After prolonged periods of darkness (100-110 min), compared with short periods (30-40 min), L-type cone horizontal cells exhibited responses similar to those obtained during dopamine application. Dim flickering or continuous light backgrounds did not mimic the effects of dopamine. Although dopamine application onto retinae after short-term darkness produced dramatic effects on L-type cone horizontal cells, little or no effect was observed when dopamine was applied while the effects of a previous dopamine application were still present or after prolonged darkness. These results suggest that interplexiform cells may release dopamine after prolonged darkness and that interplexiform cells may regulate lateral inhibitory effects mediated by L-type cone horizontal cells as a function of time in the dark. PMID- 2888123 TI - Modulation of the GABAA receptor by progesterone metabolites. AB - The naturally occurring progesterone metabolites 5 beta-pregnan-3 alpha-ol-20-one and 5 beta-pregnane-3,20-dione reversibly enhance membrane currents elicited by locally applied GABA in bovine adrenomedullary chromaffin cells. Such potentiation was not influenced by the benzodiazepine antagonist Ro 15-1788. At concentrations in excess of those necessary to evoke potentiation of GABA currents, 5 beta-pregnan-3 alpha-ol-20-one and 5 beta-pregane-3,20-dione directly activated a membrane conductance. The resulting currents were potentiated by phenobarbitone and diazepam, and abolished by the GABAA-receptor antagonist, bicuculline. On outside-out membrane patches, 5 beta-pregnan-3 alpha-ol-20-one and 5 beta-pregnane-3,20-dione activated single channel currents of similar amplitude to those evoked by GABA. The results suggest that certain naturally occurring steroids potentiate the actions of GABA and, additionally, directly activate the GABAA receptor. PMID- 2888124 TI - Models of the Na-K pump in cardiac muscle predict the wrong intracellular Na+ activity. AB - The Na-K pump in cardiac Purkinje strands has been carefully studied with voltage clamp and Na+-selective microelectrodes. In three of these studies both the rate of change of intracellular Na+ activity, a(Nai), after pump blockade, and the time constant of reduction of a(Nai) after an Na+ load were measured. These two parameters can be employed with a formalism relating pump activity to a(Nai) in order to predict the a(Nai) in the steady state. Several formalisms were tested: (a) a first-order dependence on a(Nai); (b) a model based on the assumption of a single, saturable, Na+-binding site that must be occupied for transport to occur; (c) a model based on n equivalent, saturable, Na+ binding sites per pump molecule all of which must be occupied for transport to occur. The first two models predicted an a(Nai) that is far below the value of about 6 mM that is experimentally obtained. The third model would work for n greater than or equal to 4. These results suggest that either the cardiac Na-K pump is not well described by available Na-K pump models for n less than 4 or that the measured Na+ influx rate, extrusion rate or a(Nai) are in error. PMID- 2888126 TI - Absence of age-related changes in the binding of the beta adrenergic antagonist 125I-iodohydroxybenzylpindolol in rat heart. AB - The effect of age on the density and the affinity of beta adrenergic receptors was determined in the hearts of Fischer 344 rats at three ages, 6, 12, and 24 months old. The binding of the beta adrenergic antagonist 125I iodohydroxybenzylpindolol (IHYP), was used to quantitate and characterize cardiac beta adrenergic receptors. The maximal number of binding sites (Bmax = F moles/mg of protein) were 26.3 +/- 2.5, 25.4 +/- 0.99, and 24.5 +/- 2.4 and the dissociation constants (Kd = nM) were 0.166 +/- 0.014, 0.126 +/- 0.006, and 0.135 +/- 0.015 for 6, 12, and 24 months old animals, respectively. There were no significant differences among the three ages. These results support the contention that neither beta adrenergic receptor density or affinity changes with age in the ventricles of the rat heart. PMID- 2888125 TI - Polymorphism of photopigments in the squirrel monkey: a sixth phenotype. AB - We describe here a trichromatic type of squirrel monkey that resembles Old World monkeys in having two well-separated photopigments in the red-green part of the spectrum; the cones of this phenotype have peak sensitivities close to 430, 536 and 564 nm. The existence of such animals is predicted by a genetic model that postulates three alleles for a single locus on the X-chromosome of the squirrel monkey. The three alleles correspond to three different photopigments in the red green spectral range. A male monkey, or a homozygous female, will be dichromatic, combining short-wave cones with just one of the cone types in the red-green range. But a female monkey, if heterozygous at the locus, draws any two of the three alleles from the set. X-chromosome inactivation ensures that the two alleles are expressed in different subpopulations of retinal cone, giving the monkey the basis for trichromatic colour vision. This model requires three trichromatic types of female squirrel monkey. The photopigment complements of two types have previously been reported and microspectrophotometric data are now given for the third type. Behaviourally, this third type of trichromat gives precise Rayleigh matches that are intermediate between those of the other two types of trichromat. The polymorphism of photopigments in the squirrel monkey may be maintained by the heterozygous advantage enjoyed by the trichromatic females. This would be an instructive instance of heterozygous advantage because it is a case where X-chromosome inactivation plays a crucial role in segregating the two different gene-products into different cells. PMID- 2888127 TI - Influence of neural blockages and proglumide on rat pancreatic enzyme secretion in response to intraluminal fatty acid. AB - Effects of neural blockages on pancreatic enzyme secretion in response to infusing fatty acid into the lumen were investigated using anesthetized rats, equipped with bile-pancreatic and duodenal cannulae, to evaluate the relative contribution of the neural and the hormonal mediations in the pancreatic response. Oleate (0.2 ml) was injected as a bolus into the rat duodenum, and the trypsin output in bile-pancreatic juice was monitored to determine the pancreatic enzyme secretion response with continuous return of bile-pancreatic juice to the intestine. When anticholinergic agents such as atropine sulfate and scopolamine were administrated, although basal level in pancreatic enzyme secretion fell, the increase of pancreatic enzyme secretion from basal level after stimulation by oleate was not significantly different from that of the control (no blockage). However, the ganglion blocker, hexamethonium, inhibited the pancreatic enzyme secretion in response to oleate by 94%. An adrenergic blocker, guanethidine, also led to as much of a decrease as the ganglion blocker-induced decrease. Adrenergic alpha- and beta-blockers partially, but not completely, inhibited the enzyme secretion. Adrenergic blockage also suppressed the basal level in pancreatic enzyme secretion. On the other hand, a specific CCK antagonist, proglumide, significantly inhibited pancreatic enzyme secretion induced by oleate in the presence of scopolamine. These observations suggest that pancreatic enzyme secretion in response to oleate is primarily mediated by CCK and that adrenergic modulation may play an important role in the CCK-mediated pancreatic enzyme secretion in response to oleate, although interpretation of these results may have some restriction related to anesthesia. PMID- 2888129 TI - Selective antagonism of renal hemodynamic changes induced by dopamine, DPDA, fenoldopam and quinpirole in the rat. PMID- 2888128 TI - Structure-activity analysis of five constrained somatostatin like peptides with opioid antagonist properties. PMID- 2888130 TI - Changes in rat adrenal tyrosine hydroxylase mRNA levels following chronic amphetamine administration. PMID- 2888131 TI - Mechanism of action of somatostatin in the hippocampal slice. PMID- 2888132 TI - Immunocytochemical localization of tyrosine hydroxylase in the growth cones of PC12 cells. PMID- 2888134 TI - Withdrawal syndrome following subchronic treatment with anxiolytic agents. AB - The acute administration of diazepam (0.1-2.5 mg/kg IP), sulpiride (0.5-20 mg/kg IP) and tiapride (0.5-40 mg/kg IP) to the mouse enhanced exploratory activity (rearings/line crossings) in the brightly illuminated white area of a two compartment white/black anxiety test box, with a corresponding decrease in the black, indicating an anxiolytic action. This profile of change was maintained during a twice daily administration for 7 days with diazepam (2.5 and 10 mg/kg), sulpiride (5 and 20 mg/kg) and tiapride (10 and 40 mg/kg). However, 8 and 48 hr following withdrawal of diazepam, the profile of exploratory behaviour was reversed to a preference for the black area: by 96 hr values for behaviour had returned to control levels. In contrast, an anxiolytic profile of action was maintained 8 and 48 hr following the withdrawal of sulpiride and tiapride, the values returning to control levels after 96 hr. It is concluded that a sub chronic treatment with diazepam, sulpiride and tiapride induces an anxiolytic profile of action in the mouse model, that an anxiogenic profile follows the abrupt withdrawal of diazepam but that this is not recorded following the abrupt withdrawal of sulpiride and tiapride. PMID- 2888133 TI - Changes of N-6 and N-3 fatty acids in liver from spontaneously hypertensive (SHR) and normotensive rats after diets supplemented with alpha-linolenic or eicosapentaenoic acids. AB - In spontaneously hypertensive (SHR) and normotensive rats (WKY), diets supplemented with n-3 fatty acids of different chain length (alpha-linolenic acid, LNA-C 18:3, n-3 with linseed oil and eicosapentaenoic acid, EPA-C 20:5, n-3 with cod liver oil) were fed over a period of 22 weeks. A diet with commercially available pellets served as control. After the LNA-rich diet the augmentation of LNA was most pronounced in liver triglycerides (TG) and free fatty acids (FFA), whereas the increase of EPA was most marked in phosphatidylethanolamine (PE) and phosphatidylcholine (PC) when compared with the controls. Docosahexaenoic acid (DHA) was decreased mainly in neutral lipids. Of the n-6 fatty acids linoleic acid (LA) appeared significantly depressed in TG and FFA, but increased in phospholipids. Arachidonic acid (AA), however, was lower in all lipids. In SHR and WKY fed the EPA-rich diet EPA and DHA were significantly higher as compared to the controls on a pellet diet. On the contrary, LNA was not detectable in all lipid classes. LA and AA were markedly depressed. Docosenoic acids were significantly increased. The p/s-ratio did not reflect the changes in the 20:5/20:4- and n-3/n-6-ratios. The data indicate a differential effect of dietary n-3 fatty acids of different chain length on the supply of other n-3 fatty acids. Moreover, after an LNA-rich diet divergent alterations of LA in neutral lipids and phospholipids occurred. The results are dissimilar to those obtained in adipose tissue. Blood pressure was not influenced by the diets in either SHR or WKY. PMID- 2888135 TI - Blockade by neuroleptics of water intake and operant responding for water in the rat: anhedonia, motor deficit, or both? AB - Four different neuroleptic drugs, haloperidol, metoclopramide, sulpiride and cis flupenthixol, were tested for their ability to attenuate an operant lever pressing response with water as reward and the corresponding consummatory act, i.e., the non-conditioned water intake. All four neuroleptic drugs tested more potently attenuated the operant lever-pressing response than the consummatory water intake, just as the conditioned avoidance response previously has been found to be more potently attenuated than the non-conditioned escape reaction. The results suggest that a certain class of learned behaviors, labelled operant or instrumental behaviors, are more susceptible to the attenuating effects of neuroleptic drugs than the class of behaviors labelled non-conditioned consummatory acts. It was further concluded that the attenuation of the lever pressing response could be explained by a decreased ability of the animals to initiate or perform the required operant response (i.e., a motor deficit) while the attenuated water intake caused by higher doses of the neuroleptics could be interpreted as a motivational effect (e.g., "anhedonia"). When studying the effects of the neuroleptic drugs it is therefore of great importance to know whether the behavior measured in the particular experimental design used is operant or consummatory. The implications of the findings are discussed. PMID- 2888136 TI - Self-administration of barbiturates and benzodiazepines: a review. AB - Studies of barbiturate and benzodiazepine self-administration are categorized by species and route of administration. Reinforcement, defined as self administration of drug greater than of a non-drug control, has been demonstrated most often in studies employing the IV route, and there has been greater reliability in this result for a given drug among barbiturates rather than among benzodiazepines. Most studies of PO self-administration in rodents have not demonstrated reinforcement, despite a number of behavioral manipulations to induce drug intake. Studies of PO barbiturate self-administration in monkeys have demonstrated reinforcement but recent studies of PO benzodiazepine self administration in baboons have not, although physical dependence was demonstrated. Reinforcement via the IG route has not been reliably demonstrated. Behavioral variables, including interreinforcement interval and drug self administration history, appear to be important determinants of whether or not reinforcement will be demonstrated, particularly among the benzodiazepines; but the range of conditions under which behavioral and pharmacological variables interact to promote or lessen the likelihood of self-administration of these drugs remains to be determined experimentally. PMID- 2888137 TI - Protection of CGS 10078B against ouabain-induced arrhythmia in the cat. AB - CGS 10078B (CGS; 1-[2,3-dihydro-1,4-(2S)-benzodioxin-2-yl]-5-[2,3-dihydro-1,4 (2R)- benzodioxin-2-yl]-3-(1R,5S)-aza-1,5-pentanediol methane sulfonate) is an agent with alpha- and beta-receptor and calcium channel blocking actions. To study its antiarrhythmic activity, cats were anesthetized with alpha-chloralose, ventilated, and given atropine and gallamine. CGS (10 or 20 mg/kg, i.v.) was infused 15 min prior to ouabain. Bolus injections of ouabain (25 micrograms/kg, i.v.) were given every 15 min until death (D). Some cats were pretreated with reserpine (R; 5 mg/kg, i.p.) 24 h prior to the experiment. In other cats 6 hydroxydopamine (6-OHDA; 20 mg/kg, i.v.) was administered 3 days prior to CGS 20 mg/kg and ouabain. Data were compared with those of Lathers [Eur. J. Pharmacol. 64: 95, 1980], i.e., with 12 cats who received only ouabain and with 11 pretreated with timolol (T; 5 mg/kg, i.v.) prior to ouabain. After CGS (10 or 20 mg/kg, i.v.), but just prior to the first dose of ouabain, the blood pressure (BP) was decreased (p less than 0.05) from control (165 +/- 6 vs. 96 +/- 7, and 136 +/- 5 vs. 90 +/- 10 mm Hg, respectively). Comparable heart rate (HR) values were also decreased (p less than 0.05) from 225 +/- 17 to 166 +/- 14 and from 193 +/- 8 to 152 +/- 6 beats/min. 11 min after T, BP and HR had decreased (p less than 0.05) from 133 +/- 6 to 103 +/- 7 mm Hg and from 134 +/- 4 to 104 +/- 6 beats/min, respectively. Ouabain did not influence these decreases in BP and HR. CGS (10 or 20 mg/kg, i.v.) increased (p less than 0.05) the time to ouabain induced arrhythmia (AR) and D. The magnitude of the protection appeared to be similar to that afforded by T. R given prior to CGS (20 mg/kg, i.v.) also increased the time to ouabain-induced AR and D while 6-OHDA increased the time to AR. The CGS protection against ouabain-induced AR was still present in animals pretreated with R or 6-OHDA. This indicates that the antiarrhythmic affect is not dependent upon adrenergic neuronal blockade. PMID- 2888138 TI - Blocking effects of nipradilol on vasoconstrictor responses to periarterial nerve stimulation and alpha-adrenoceptor agonists in isolated and perfused canine mesenteric arteries. AB - The stainless steel cannula inserting method was used to observe effects of nipradilol and prazosin on responses to periarterial electrical nerve stimulation and intraluminal administration of noradrenaline or phenylephrine in isolated and perfused canine mesenteric arteries. With small doses, nipradilol slightly potentiated vasoconstrictor responses to noradrenaline, but not periarterial stimulation. With a relatively large dose, nipradilol almost uniformly suppressed both periarterial stimulation-induced and noradrenaline- or phenylephrine-induced vasoconstriction. On the other hand, prazosin inhibited noradrenaline-induced vasoconstriction at small doses but not periarterial nerve stimulation-induced vasoconstrictions. At any doses, prazosin strongly inhibited noradrenaline induced constrictions more markedly than periarterial stimulation-induced constrictions. It is concluded that nipradilol has a dominant inhibitory property on periarterial nerve stimulation-induced constriction in isolated canine mesenteric arteries. PMID- 2888139 TI - H2-receptor antagonists as inhibitors of oxidative drug metabolism in vivo. PMID- 2888140 TI - Drugs other than H2-receptor antagonists as clinically important inhibitors of drug metabolism in vivo. PMID- 2888141 TI - Comparative effects of H2-receptor antagonists on drug metabolism in vitro and in vivo. PMID- 2888142 TI - Metabolic characterization of human liver microsomal cytochromes P-450 involved in the oxidation of debrisoquine, bufuralol and the carcinogen 2 acetylaminofluorene. PMID- 2888143 TI - Effect of temperature on sulfite-mediated dark reversion of urocanase in Pseudomonas putida. PMID- 2888144 TI - [Neuroleptic modification of basic schizophrenic disorders]. AB - After a short review of the German literature dealing with basal schizophrenic disturbances, the authors present the results of their own studies involving 135 schizophrenics. A large inventory of statistical methods is used to present the findings gained during differential neuroleptic therapy by means of the Frankfurt complaints questionnaire and the structured psychopathic assessment system (SPES A). The studies indicate that basal schizophrenic disturbances are accessible to (differential) neuroleptic influence. PMID- 2888145 TI - The biological basis of benzodiazepine dependence. PMID- 2888146 TI - A review of the biochemical and neuropharmacological actions of lithium. AB - The pharmacological actions central to the therapeutic effects of lithium have not yet been established, despite almost 40 years of clinical use and scientific investigation. We review the biochemical and neuropharmacological data relating to this problem and attempt to identify profitable areas for further research. PMID- 2888147 TI - Computerized axial tomographic studies following long-term use of benzodiazepines. AB - Computerized axial tomography was used to compare sex and age-matched groups of controls and long-term benzodiazepine users for evidence of cerebral atrophy. No statistically significant differences were found. PMID- 2888148 TI - The nucleus accumbens and antidepressants: modulation of ergometrine-induced hyperactivity by typical and atypical antidepressants and neuroleptics in rats. AB - This study assesses the behavioural significance of the (-)sulpiride binding sites in the rat nucleus accumbens that bind antidepressants with high affinity and neuroleptics with low affinity. The effects were measured by intra-accumbens injections of typical and atypical antidepressants or neuroleptics, either given alone or in combination with ergometrine (1 microgram/0.5 microliter per side) on rat locomotor activity in a familiar environment. In addition, the after-effects of the combined ergometrine-drug treatment upon locomotor activity were analyzed. The antidepressants shared a common profile of effects. Thus, none of the antidepressants significantly altered locomotor activity in naive rats. Moreover, each antidepressant produced after-effects which were similar to those elicited in the acute ergometrine experiments. However, some antidepressants (amitriptyline and zimelidine) potentiated the ergometrine response, while other antidepressants (desipramine, mianserin and clorgyline) attenuated this response. (-)Sulpiride (0.5 microgram) decreased the ergometrine response when given together with ergometrine or 48 h earlier. Haloperidol had to be given in a dose that was 20 times higher than that of (-)sulpiride in order to be effective. Clozapine (1-10 micrograms) failed to alter the ergometrine response when given together with ergometrine. Only (-)sulpiride produced a dose-dependent attenuation of locomotor activity in naive rats. The present data are discussed in terms of the hypothesis that drugs with antidepressive effects mediate their behavioural effects via mesolimbic (-)sulpiride binding sites. PMID- 2888149 TI - Effects of neuroleptic drugs, clonidine and lithium on the expression of conditioned behavioral excitation in rats. AB - Rats with a history of daily (21 days) amphetamine (2.5 mg/kg) treatment showed enhanced activity when under placebo in their amphetamine-associated environment. We found that this conditioned effect was reduced by haloperidol (0.06; 0.125; 0.25 mg/kg), pimozide (0.25; 0.5 mg/kg) and sulpiride (8; 16; 32 mg/kg) but only at doses similar to or, in the case of pimozide, higher than those required to antagonize the unconditioned stimulant effects of amphetamine (2.5 mg/kg). Conversely, we observed that clonidine (7; 15; 30; 60 micrograms/kg) or lithium regimen (between days 15 and 21) leading to lithium plasma levels of 1.3 +/- 0.1 mEq/l, abolished amphetamine-conditioned hyperactivity but did not affect the unconditioned stimulation of amphetamine or locomotor activity in control rats. Moreover, we found that hyperactivity induced by the daily anticipation of food delivery shared identical pharmacological sensitivity with the behavioural excitation produced by a conditioning history with amphetamine. In light of the antimanic properties of lithium and clonidine and the ability of this latter drug to reduce noradrenergic transmission, our findings raise the possibility that incentive activity may model noradrenergic-dependent aspects of mania. PMID- 2888151 TI - Impairment of decision making in rats by diazepam: implications for the "anticonflict" effects of benzodiazepines. AB - Benzodiazepines, used in the clinic as anxiolytics, have in animal models been found specifically to attenuate behavioural suppression caused by response contigent aversive stimuli, non-reward or novelty. The effects have been interpreted in more general terms as "behavioural disinhibition" or "response perseveration" or in more specific terms as reduced "reward delay" or as an attenuation of a "behavioural inhibition system". In a recent publication we have described an experimental test in which decision making in the rat can be studied. The model is derived from ethology, in particular from optimal foraging theory. In order to solve the task, the animal must choose correctly between two options. For each option the probability of its resulting in a reward (water) has to be estimated on the basis of available information and to be related to the cost of performing it. We found that diazepam, in a dose that did not significantly affect the ability to perform the options per se, caused a strong impairment when these options, on the basis of available information, had to be combined into functional sequences in a decision making procedure. The results obtained cannot be explained on the basis of disinhibition or response perseveration. The hypothesis is advanced that benzodiazepines alter decision making in a more nonspecific may, by, for example, affecting the evaluation of the learned significance of stimuli in the environment. PMID- 2888150 TI - The time course of neuroleptic therapy for psychosis: role of learning processes and implications for concepts of psychotic illness. AB - In neuroleptic therapy for psychotic illness, clinical improvement is produced more slowly than is central dopamine blockade, and its time course is highly variable between patients. A theory of neuroleptic-responsive psychotic illness thus requires more than dopamine blockade, though that appears to be the first step in the therapeutic process. Some previous explanations given for the protracted time course of neuroleptic therapy are discussed, with emphasis on the hypothesis of delayed inactivation of midbrain dopamine neurones. For various reasons all explanations are unsatisfactory. An alternative hypothesis is proposed in which neuroleptic-responsive psychoses are seen as arising from a hyperactivity of the associations of thought. Such psychoses thus involve a disorder of a high-level learning process, namely the elaboration of memories of thoughts and beliefs. Neuroleptic drugs are envisaged to remedy this process, but not to eradicate the abnormal memories already formed. Psychotic symptoms may thus outlast the start of neuroleptic therapy by many weeks. It is suggested that the pharmacological characteristics of the hypothetical learning process involved in generating psychotic symptoms are analogous to those of a simpler learning process, defineable in animal experiments - namely, the reward component in instrumental conditioning. A preliminary case is made that the relative potency of different neuroleptic drugs in antipsychotic therapy can better be predicted by their relative potency in retarding such a variety of learning, than by other behavioural tests of these drugs. PMID- 2888152 TI - Comparison of the effects of quazepam and triazolam on cognitive-neuromotor performance. AB - The pharmacological activity of quazepam, a BZ1 specific benzodiazepine, was compared to the effects of triazolam, a BZ1, BZ2 nonspecific benzodiazepine. Using a double-blind procedure, single oral doses of quazepam (15 or 30 mg), triazolam (0.5 or 1.0 mg) and placebo were administered to 21 healthy young men according to a random Latin square design balanced for order of drug administration. The drug effects on the performance of motor coordination and cognitive tasks were monitored for 7 h following drug ingestion. The results did not indicate any differential effects on cognitive-neuromotor performance for the BZ1 specific quazepam and 2-oxoquazepam compared with the BZ1, BZ2 nonspecific N desalkylflurazepam metabolite. The impairment magnitude for 30 mg quazepam was closer to that of 0.5 mg triazolam. The onset of the initial drug effect was considerably slower for quazepam than for triazolam. The time course of the impairment profiles for the tasks was compared to pharmacokinetic data from previous studies and suggested that published pharmacokinetic rate constants explain only a limited portion of the impairment time course. In particular, the performance scores were already showing recovery from peak impairment 2 h post drug ingestion, although quazepam's potent N-desalkylflurazepam metabolite has been found to maintain a maximum plateau level from 2 to 24 h. PMID- 2888153 TI - Evidence that the amygdala is involved in benzodiazepine and serotonergic effects on punished responding but not on discrimination. AB - Interactions between the benzodiazepines (BZs) chlordiazepoxide (CDP) and midazolam (MDZ), the BZ antagonist R0 15-1788, the inverse BZ receptor agonists CGS 8216 and FG 7142, gamma-aminobutyrate (GABA), serotonin (5-HT), the 5-HT2 antagonist methysergide and the putative 5-HT agonist 8-hydroxy-2-(di-n propylamino) tetralin (8-OH-DPAT) were investigated using peripheral and intra amygdaloid treatments. A multiple schedule consisting of rewarded, nonrewarded (Time out: TO) and conflict periods was used to compare in parallel effects on successive discrimination between rewarded and nonrewarded periods and punished responding. The three components were presented in both a fixed order (Experiment 1) and a random order (Experiments 2 and 3). Intra-amygdaloid treatments with GABA and the BZs selectively increased rates of punished responding. CDP given systemically, on the other hand, increased both TO and conflict rates, suggesting an additional impairment of discrimination, which was more marked in the random than the fixed order condition. R0 15-1788, CGS 8216 and FG 7142 given by both routes counteracted the anti-conflict effects of CDP given centrally or systemically. However increases in TO rates induced by IP CDP were antagonized only by IP treatments with these compounds. The two inverse agonists, but not R0 15-1788, also counteracted increases in punished responding which were found after intra-amygdaloid GABA infusions. In Experiments 2 and 3 where baseline rates of pressing in Conflict periods were sufficiently high to detect decreases, CGS 8216 and FG 7142 reduced responding below control level, suggesting a specific anxiogenic activity. Evidence for effects of R0 15-1788 by itself was inconclusive. 5-HT injected into the amygdala also reduced punished responding below control level, whereas methysergide increased it with both central and peripheral treatment. Effects of 8-OH-DPAT varied according to route of administration. With IP treatment Conflict rates were increased, but after amygdaloid infusion both TO and Conflict rates were marginally reduced below control level, with a more consistent depression of punished responding. These results provide evidence that effects of BZs on punished responding are mediated by a GABAergic system which includes the lateral/basolateral amygdala, but which does not participate in BZ-induced disruption of discrimination. They also indicate that the antagonistic effects of CGS 8216 and FG 7142 involve a decrease in GABA transmission, and that these compounds may also be anxiogenic.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2888154 TI - Effects of ethylketazocine and morphine alone and in combination with naloxone on schedule-controlled behavior in pigeons. AB - The behavioral effects of morphine and ethylketazocine were compared in pigeons responding under multiple fixed-interval, fixed-ratio schedules of food presentation. Both morphine and ethylketazocine produced dose-related decreases in rates of responding maintained under either schedule. Maximal effects of morphine were observed about 15-45 min after injection and typically lasted the entire session (about 60 min). Effects of ethylketazocine had a faster onset (maximal effects were observed within 15 min after injection), and shorter duration (effects diminished within the session). Ethylketazocine and morphine had similar potencies. Dose-effect curves for both drugs were shifted to a similar degree by naloxone. PMID- 2888155 TI - Determinants of benzodiazepine brain uptake: lipophilicity versus binding affinity. AB - Factors influencing brain uptake of benzodiazepine derivatives were evaluated in adult Sprague Dawley rats (n = 8-10 per drug). Animals received single intraperitoneal doses of alprazolam, triazolam, lorazepam, flunitrazepam, diazepam, midazolam, desmethyldiazepam, or clobazam. Concentrations of each drug (and metabolites) in whole brain and serum 1 h after dosage were determined by gas chromatography. Serum free fraction was measured by equilibrium dialysis. In vitro binding affinity (apparent Ki) of each compound was estimated based on displacement of tritiated flunitrazepam in washed membrane preparations from rat cerebral cortex. Lipid solubility of each benzodiazepine was estimated using the reverse-phase liquid chromatographic (HPLC) retention index at physiologic pH. There was no significant relation between brain:total serum concentration ratio and either HPLC retention (r = 0.18) or binding Ki (r = -0.34). Correction of uptake ratios for free as opposed to total serum concentration yielded a highly significant correlation with HPLC retention (r = 0.78, P less than 0.005). However, even the corrected ratio was not correlated with binding Ki (r = -0.22). Thus a benzodiazepine's capacity to diffuse from systemic blood into brain tissue is much more closely associated with the physicochemical property of lipid solubility than with specific affinity. Unbound rather than total serum or plasma concentration most accurately reflects the quantity of drug available for diffusion. PMID- 2888157 TI - Postinfarction angina. AB - In conclusion, the PIA patient is at high risk, with higher early as well as late mortality. The pathophysiology of PIA is complex and may vary from patient to patient. The concepts of ischemia at a distance and ischemia in the infarct zone have led to a better understanding of early PIA. Coronary spasm may play an important role in most PIA patients as in the general population of patients with angina pectoris. Medical therapy is efficacious in many, although it may on rare occasion aggravate myocardial ischemia. Urgent coronary arteriography is generally safe and should be performed as soon as possible for medically refractory PIA. CABG appears to be safe in experienced hands, but its timing must be individualized. The IABP should be reserved for more unstable patients for fear of vascular complications. Randomized controlled trials such as the BARI Trial will further compare PTCA with CABG. PMID- 2888156 TI - Neuroleptic-induced oral dyskinesias: effects of progabide and lack of correlation with regional changes in glutamic acid decarboxylase and choline acetyltransferase activities. AB - The development of vacuous chewing movements (VCMs), and changes in glutamic acid decarboxylase (GAD) and choline acetyltransferase (ChAT) activities in extrapyramidal nuclei were examined in rats treated chronically with neuroleptics. Animals were injected with flupenthixol (FLU) or haloperidol (HAL) decanoate for 16, 40 or 48 weeks and were then sacrificed. Another group of rats was treated with FLU or HAL for 48 weeks, and then withdrawn from the neuroleptics for 16 weeks before sacrifice. VCMs were assessed weekly, and the effects of the GABA agonist progabide on VCMs and locomotor activity were examined. GAD and ChAT activities were determined at death. The concentrations of Calbindin D28K (CaBP) and parvalbumin (PV) were determined in rats receiving 48 weeks of neuroleptic treatment. VCMs first appeared after 8-10 weeks of neuroleptic administration, reached asymptotic rates after 18-20 weeks, and then remained stable for the remainder of the chronic drug administration period. During withdrawal, there was a steady decline in the VCM rate. The GABA receptor agonist progabide reduced VCMs and locomotor activity. Significant decreases in nigral GAD activity were observed after 40, but not after either 16 or 48 weeks of neuroleptic administration. CaBP and PV were unchanged after 48 weeks of neuroleptic treatment. In addition, ChAT activities in 16, 40 or 48 week treated animals did not show consistent changes after either neuroleptic. Chronic neuroleptic administration followed by 16 weeks of withdrawal also did not have any significant effects on GAD or ChAT activity in any of the brain areas examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888158 TI - Myocardial infarct expansion, infarct extension, and reinfarction: pathophysiologic concepts. AB - Infarct expansion and infarct extension are events early in the course of myocardial infarction with serious short- and long-term consequences. Infarct expansion, disproportionate thinning, and dilatation of the infarct segment probably begin within hours of acute infarction and usually reach peak extent within seven to 14 days. Clinical data suggest that infarct expansion occurs in approximately 35% to 45% of anterior transmural myocardial infarctions and to a lesser extent in infarctions at other sites. Although expansion usually develops in large infarcts, the extent of transmural necrosis rather than absolute infarct size predicts its occurrence. Expansion has an adverse effect on infarct structure and function for several reasons. Functional infarct size is increased because of infarct segment lengthening, and expansion results in over-all ventricular dilatation. Thus, patients with expansion of an infarct have poorer exercise tolerance, more congestive heart failure symptoms, and greater early and late mortality than those without expansion. Infarct rupture and late aneurysm formation are two additional structural consequences of infarct expansion. Experimental and clinical data suggest that the incidence and severity of expansion can be modified by interventions. Increased ventricular loading conditions and steroidal and nonsteroidal antiinflammatory agents make expansion more severe. Reperfusion of the infarct segment and pharmacologic interventions that decrease ventricular afterload lessen the severity of expansion. Previous myocardial infarction and preexisting ventricular hypertrophy may also limit the development of infarct expansion. Infarct extension is defined clinically as early in-hospital reinfarction after a myocardial infarction. The pathologic finding of infarct extension is necrotic and healing myocardium of several different recent ages within the same vascular territory. Although this pathologic criterion usually cannot be verified, studies employing invasive and noninvasive assessment of patients with early reinfarction provide evidence that the new myocardial injury is usually in the same vascular risk region as the original infarction. A variety of different criteria have been applied in the clinical diagnosis of infarct extension, and this has resulted in a large range of estimated frequencies from under 10% to as high as 86%. High estimates are found in studies using one or two nonspecific criteria such as ST segment shift or reelevation of total CK. The lowest rates have been found when combinations of criteria are used.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2888160 TI - RBC-choline: a biological marker of the outcome of lithium prophylaxis? AB - We explored whether the elevation of RBC-choline and choline ratio (RBC choline/plasma-choline) by lithium is a specific effect of lithium, whether these choline parameters are characteristics of the individual patient, and whether they are related to prophylactic lithium response. In lithium-treated patients RBC-choline and choline ratio were highly elevated compared with untreated controls. In contrast, both values were slightly decreased in patients on antidepressants, and essentially unchanged in patients on neuroleptics. Repeated measurements showed that choline parameters were fairly stable in the individual patient. The interindividual variance was significantly greater than the intraindividual variance. In 58 affective disorder patients with established lithium response, high choline ratios were found to be associated with a poor outcome of stabilizing therapy with lithium. This finding was replicated in a new sample of 15 bipolar patients. If confirmed, it could be an important clue as to the mode of action of lithium. PMID- 2888159 TI - Comparison of withdrawal of buspirone and diazepam: a placebo controlled study. AB - In a 8-week double-blind placebo controlled study, 48 outpatients with generalized anxiety disorder were randomized to diazepam, buspirone, a non benzodiazepine anxiolytic, or placebo. During the treatment phase of 4 weeks duration diazepam was found to be significantly better than placebo and buspirone. Following abrupt withdrawal by placebo substitution the diazepam group showed a gradual relapse maximal after two weeks while the buspirone and the placebo groups did not differ. There were more cases of rebound anxiety with diazepam as compared to buspirone or placebo. In addition, there were three early terminations related to rebound anxiety in the diazepam group while there were none in the placebo and buspirone groups. There were significantly more new symptoms in the diazepam group than in the placebo or buspirone group. PMID- 2888161 TI - Dysregulation of neuroendocrine crossroads: depression, circadian rhythms and the retina--a hypothesis. AB - The pathophysiology of depression and the mechanism of action of lithium and other antidepressant drugs involve alterations in circadian rhythms. These include changes in both the intrinsic rhythm of circadian oscillators and in the sensitivity of the retina to LIGHT. The retina in humans is the only photoreceptor for circadian entrainment. The retinal-hypothalamic-pineal axis is the essential pathway for neuronal entrainment of rhythms which use light as a phase cue. A common substance throughout this axis in many species is MELATONIN. Retinal melatonin has been implicated in regulation of the sensitivity of the retina to light. The hypothalamus, at THE NEUROENDOCRINE CROSSROADS, has a central role in the integration of neurotransmitters and hormones in circadian rhythms. DYSREGULATION of the hypothalamic-pituitary-adrenal, as well as gonadal, axes has been documented in depressed patients. Abnormalities in circulating melatonin have also been found in patients with affective disorders. It is speculated that the availability of melatonin along the retinal hypothalamic-pineal axis may have important implications in the genesis of affective disorders. More specifically--is there a latent biochemical defect which causes a phase shift and change in circadian rhythms of melatonin and/or other neurotransmitters in the retina which then alters the sensitivity of the retina to light (for the visible spectrum) which in turn desynchronizes all other biological rhythms thus disrupting mental well-being? We suggest that variations of retinal photosensitivity in humans can be measured by using a visual testing system, and that depressed patients might show changes in photosensitivity which could be corrected when treated with lithium and/or antidepressants. It is our working hypothesis that the primary defect in depression may be a change in retinal function, and that behavioural and neuroendocrine concomitants of this disorder are secondary events. PMID- 2888162 TI - Behavioural and combined therapy in panic states. AB - This review will focus only on those paradigms for treatment of panic states with agoraphobia. Until recently the behaviour therapy literature has completely ignored panic disorder and has focused exclusively on the agoraphobic aspect of this syndrome. To summarize the behavioural therapy of panic disorder and agoraphobia, it appears that exposure is in the short run the most effective behavioural paradigm in agoraphobia. However, when contrasted with cognitive approaches it does not appear to be as effective in the treatment of panic disorder. In conclusion, it is unclear whether we can speak of antiphobic medications. Certainly studies of imipramine, chlomipramine, monoamine oxidase inhibitors, and alprazolam have demonstrated an anti-panic affect of medications and a subsequent improvement in phobic avoidance. However, when exposure is not made a part of the treatment, there is a much poorer resolution and a tendancy for the patient to relapse. PMID- 2888163 TI - Exercise-induced hyperphagia in the hamster is associated with elevated plasma somatostatin-like immunoreactivity. AB - Syrian golden hamsters when allowed free access to food and an exercise wheel will run long distances and develop hyperphagia and accelerated linear body growth with high circulating levels of growth hormone and insulin. Somatostatin, a widely distributed brain-gut neurohormonal peptide, modulates nutrient absorption and may regulate food intake. To examine the role of circulating plasma somatostatin-like immunoreactivity (SRIF-LI; pg/ml) in exercise induced hyperphagia 4 groups of animals were studied; an unrestricted exercise group (279.0 +/- 107.7, n = 10); a sedentary group (121.1 +/- 40.8, n = 8); a restricted exercise group (107.7 +/- 12.4, n = 6); and a restricted no exercise group (115.5 +/- 45.9, n = 9). Thus, the unrestricted exercise group has a significantly elevated SRIF-LI concentration (P less than 0.01) while there was no difference between the other 3 groups. The elevation of plasma SRIF-LI in the unrestricted exercise group may represent a response to modulate increased nutrient entry in this group or may represent an incompletely effective satiety signal. PMID- 2888164 TI - Kawasaki syndrome: a 1986 perspective. AB - The history of Kawasaki Syndrome is reviewed from its first description as a rare but benign disease in Japan to its current recognition as a multisystem vasculitis with predilection for arthritis and coronary disease occurring with increasing frequency in diverse areas of the world. Recent studies on efficacy of intravenous gamma globulin therapy are described. PMID- 2888165 TI - [Superiority of gammaglutamyl transferase in comparison with alkaline phosphatase in the enzymatic study of granulomatous hepatitis]. PMID- 2888167 TI - Regulation of growth hormone secretion from human fetal pituitaries: interactions between growth hormone releasing factor and somatostatin. AB - Using an explant culture system, we have demonstrated that human somatotropes respond to growth hormone releasing factor (GRF) and somatostatin (SRIF) from as early as 9.5 weeks of fetal age. Responsiveness to GRF increases significantly as a function of age up to midgestation while SRIF inhibition of basal growth hormone (GH) release does not change. SRIF has little effect on GRF-stimulated GH secretion from early gestation pituitaries, but its ability to block GRF stimulation gradually increases with fetal age from 9.5 to 16 weeks. The response to GRF remains predominant throughout this developmental period: 100 times more SRIF than GRF must be added to the cultures in order to block the GRF stimulatory effect and maintain GH secretion at basal (control) levels. Finally, adding SRIF 30 min prior to the GRF does not increase the inhibitory activity of SRIF. Our data suggest that the mechanisms that permit an interaction between GRF and SRIF are developing, but slowly, in the early to midgestation human fetal somatotrope and that GRF stimulatory pathways predominate. This may help to explain the very high levels of GH in fetal serum during the first half of gestation. PMID- 2888166 TI - [The ontogeny of hormones of the somatotrophic axis]. AB - The ontogenesis of the somatotropic function involving its regulatory hormones is considered from an anatomical and functional point of view. Embryogenesis of the hypothalamo-pituitary unit involving development of the hypothalamo-hypophyseal portal system is complete during early fetal life as shown in a certain number of mammalian species. The maturation of the neuroendocrine mechanisms controlling the secretion of fetal pituitary growth hormone is analyzed in the present paper. Corticosteroids may act directly on the differentiation of the somatotropic cells. During fetal life, the plasma level of GH is always higher than after birth. Despite large gaps in our knowledge, SRIF may play a prominent part in the regulation of the somatotropic function, sometimes mediating the effect of other factors, and GRF may also be active during late gestation. However, maturation is not complete until after birth especially that of somatomedins as well as the pulsatile release of GH. PMID- 2888168 TI - Effects of hypothalamic hormones (GRF, TRH, somatostatin) and insulin-like growth factor I on growth hormone secretion from prepubertal male lamb pituitary cultures. AB - We have examined the regulation of GH secretion from monolayer cultures of prepubertal male lamb anterior pituitary cells. Growth hormone-releasing factor (GRF 1-44) stimulated GH release in a dose-related manner: the maximal effective dose was 10(-10) M, which caused a 500% increase in basal GH secretion, while the half-maximal effect was reached with a dose of 2.5 x 10(-11) M (ED50). Thyrotropin-releasing hormone (TRH) also elicited a dose-dependent stimulation of GH secretion, although it was approximately 1000 times less potent than GRF. GRF and TRH did not have additive or synergistic effects on GH secretion. Somatostatin (SRIF) at a concentration of 10(-7) M maximally inhibited basal GH release to 40% of that of the control; the ED50 was 2.0 x 10(-9) M. Moreover, 10( 7) M SRIF blocked the stimulation of GH secretion induced by 10(-8) M GRF. However, when the cells were incubated with these two peptides at an identical concentration (10(-8) M), GH secretion was stimulated significantly above control values. When added at the same concentration (10(-7) M, TRH ans SRIF nullified their respective effects. A dose of 100 ng/ml of synthetic IGF-I was without effect on basal GH release, but significantly decreased 10(-9) M GRF-induced stimulation of GH secretion. these data indicate that in prepubertal male lambs: the stimulatory effect of GRF is predominant over the inhibitory effect of SRIF, somatostatin inhibits TRH stimulation of GH secretion in vitro, and IGF-I may control GH secretion by modulating GRF effects at the pituitary level. PMID- 2888169 TI - Biotechnology in the potential practical application of somatotrophic hormones for improving animal performance. AB - The use of biotechnology now allows adequate supplies of previously scarce substances. This has enabled evaluation of some of these substances as enhancers of animal performance. Growth hormone (GH) shows promise as a stimulator of lactation in a number of species, but its effects on the stimulation of growth are somewhat equivocal. Somatocrinin, by virtue of its GH- releasing activity, may also be potentially useful, though to date the effects of somatocrinin administration have been less promising than those for GH directly. Somatomedin (IGF-1), as the active mediator of GH, might be expected to be useful in growth promotion but, as yet, it has not been convincingly demonstrated to stimulate growth in normal animals. All these hormones have the major drawback that, until a suitable slow-release/delivery mechanism is available, they need to be administered very frequently. An alternative approach, immuno-neutralization of the growth inhibiting effects of somatostatin, has been demonstrated to enhance growth; although at present still requiring multiple treatments such a technique potentially has many advantages. PMID- 2888170 TI - Effect of growth hormone-releasing factor (1-29)NH2 and thyrotropin-releasing factor on growth hormone release in lactating sows. PMID- 2888171 TI - [Diet in chronic renal insufficiency--current status]. PMID- 2888172 TI - [Physiopathologic correlations regarding changes in the lipid spectrum and hemostasis in patients with essential arterial hypertension]. PMID- 2888173 TI - [Pharmacokinetic evaluation of the pharmacodynamic effect of digoxin, following the administration of a single intravenous dose to healthy volunteers]. PMID- 2888174 TI - [Clinical study on the efficacy of drug therapy in sick sinus node syndrome]. PMID- 2888175 TI - [Study on the incidence and anatomo-clinical forms of digestive alcoholic pathology in hospitalized patients]. PMID- 2888176 TI - [Problems of positive and differential diagnosis of gastric cancer in the stage of gastric mucosal manifestations]. PMID- 2888177 TI - [Acute renal insufficiency in pregnancy and the postpartum period]. PMID- 2888178 TI - [Seroimmunologic and bacteriologic methodology for evaluating the diagnosis of polyarthropathies in major collagenoses]. PMID- 2888179 TI - [Activity of T, NK and K lymphocytes in two immunodeficiency syndromes]. PMID- 2888180 TI - [Treatment of the hypertensive crisis]. PMID- 2888181 TI - [Amebiasis: recent progress]. PMID- 2888182 TI - A pharmacological approach to the analgesizing mechanism of somatostatin in cluster headache. AB - Vasodilation, conjunctival and nasal edema as well as miosis are symptoms associated with cluster headache (CH) attacks. Similar symptomatology is caused by substance P (SP) release from peripheral trigeminal nerve endings. The symptomatic effect of somatostatin (SRIF) during CH attacks was attributed to the inhibition of SP release from trigeminal neurons. This study was designed to evaluate both the vascular effect of SRIF on the dorsal hand vein and SRIF plasma levels prior to and after subcutaneous and intranasal administration in CH patients. A powerful venoconstriction and tachyphylaxis were demonstrated when SRIF was administered both as bolus and infusion. Plasma levels of SRIF in CH sufferers were lower than in control subjects. Subcutaneous and intranasal SRIF administrations induced maximal plasma levels after 5 and 10 min, respectively. These data suggest that SRIF plays an important role during CH attacks; however, its exact mechanism of action is still to be defined. PMID- 2888184 TI - Gastric neuroendocrine cell hyperplasia after treatment with the long-acting, potent H2-receptor antagonist SK&F 93479. AB - The time course and dose response of the neuroendocrine cell hyperplasia in the oxyntic mucosa of the rat was examined after treatment with the potent, long acting H2-receptor antagonist SK&F 93479 at doses of 0 and 1000 mg/kg orally for 1, 3, 7, and 14 days and at doses of 0, 40, 200, and 1000 mg/kg orally for 1 and 6 months. The number of oxyntic neuroendocrine cells (chromogranin-positive) increased after 7 days of treatment. In the 1- and 6-month studies with doses of 1000 mg/kg, the grading for the number of oxyntic chromogranin-positive cells was 2.5 to 3 times the control levels, and they were distributed mostly throughout the mucosa, whereas at lower doses, which did not produce carcinoid tumours at 2 years, the neuroendocrine cells were distributed in the lower half of the mucosa with 1.5- to 2-fold increases in grades for cell numbers. Increases in cell numbers and cell distribution may be useful factors in the evaluation of the neuroendocrine cell hyperplasia found in, for example, the Zollinger-Ellison syndrome and chronic atrophic gastritis, in which hypergastrinaemia and fundic neuroendocrine cell hyperplasia are present. PMID- 2888183 TI - A double-antibody sandwich ELISA for the detection of Entamoeba histolytica antigen in stool samples of humans. AB - A double-antibody sandwich ELISA was developed to detect detergent-solubilized antigens of Entamoeba histolytica in stool samples of humans. The test system was evaluated for its methodical and diagnostic sensitivity and specificity. In recovery experiments the lower limit of detection was 400 ng E. histolytica (HK9) protein/ml stool, corresponding to approximately 2000 amoebic trophozoites/ml stool. Samples of 97 patients with suspected intestinal amoebiasis were examined. Specific antigens were detected by ELISA (= positive reaction) in 14 (93%) out of 15 stool samples containing trophozoites of E. histolytica. In contrast, 68 (93%) of 73 samples with other protozoa, including Entamoeba coli, E. hartmanni, Endolimax nana, Iodamoeba buetschlii and Giardia lamblia, did not react in the test system (= negative reaction). The test was shown to detect only trophozoites of E. histolytica and not the cyst stage. This fact could facilitate the differentiation between cyst carriers and persons excreting trophozoites. The results of this preliminary study justify a further large scale evaluation of the test system. PMID- 2888185 TI - The effects of 75 mg HOE 760, a novel H2-receptor antagonist, on daytime peptone stimulated and nocturnal gastric acid output in healthy volunteers. AB - The effects of HOE 760, a highly specific H2-receptor antagonist, on daytime peptone-stimulated and nocturnal gastric acid output were studied (randomized, double-blind crossover) in 10 healthy men. Acid output was monitored at lunch (1200 h to 1400 h) and dinnertime (1800 h to 2000 h) by continuous automatic intragastric titration; from midnight to 0600 h, output was measured by titration of manually aspirated gastric contents. After a 75-mg oral dose (capsule containing HOE 760 granules) at 0800 h peptone-stimulated acid output decreased for at least 12 h. Compared with placebo, significant reductions (p less than 0.05) of 86% and 32% were observed 4-6 h and 10-12 h after drug administration. After another dose of 75 mg at 2100 h nocturnal acid output was significantly reduced (p less than 0.05) by 88%; gastric pH was increased by about 2 units throughout the night. HOE 760 was well tolerated. No adverse reactions occurred; no clinically relevant changes were noted in haematologic, biochemical, urinary, or electrocardiographic variables. PMID- 2888186 TI - Basal upper gastrointestinal motility in healthy people. PMID- 2888187 TI - Opioids and opioid receptors in peripheral tissues. AB - Opioid peptides belonging to the enkephalin, beta-endorphin or dynorphin family, acting on specific opiate receptors may be found in peripheral tissues. Enkephalins have a widespread peripheral distribution, while beta-endorphin and dynorphin may be found locally in the enteric nervous system. The peptides of the various families are formed from specific precursor molecules. Apart from the enteric nervous system, opioids are also found in the adrenal medulla as well as in several autonomic ganglia. There is some evidence of three different classes of opioid receptors in peripheral tissues, i.e. mu-, delta- and kappa-receptors. These receptors are not only found on enteric nervous and mucosa cells but also on various cells in the immune system where opioid peptides seem to have important actions and appear to link the neuroendocrine and immune systems to control immunological functions. The physiological as well as the pathophysiological role of opioid peptides in the periphery is gradually being elucidated and, based on such knowledge, new therapeutic implications in gastrointestinal or immune diseases may be developed. PMID- 2888188 TI - Matching of host genotype and serotypes of Coxsackie B virus in the development of juvenile diabetes. AB - Thirty-six consecutive paediatric patients (0-16 years old) with recently contracted juvenile diabetes (IDDM) during 1982-84 were included in the study. Sera were assayed for recent or current Coxsackie B virus (CBV) infection using a specific and sensitive IgM RIA. Eighteen patients (50%) had IgM against CBV 1-5. The patients were also assayed for restriction fragment length polymorphism (RFLP) patterns with DNA probes coding for HLA-DR and DQ beta chains. The CBV positive patients (n = 18) had either RFLP patterns associated with HLA-DR 3 or 4 or HLA-DQ patterns III or IV beta. Two of the CBV negative patients had neither HLA-DR 3 nor DR 4 and four of them had neither DQ patterns III nor IV. Eleven out of 18 CBV-positive patients had HLA-DQ III and DR 3 (61%) versus 5 out of 18 (28%) of the CBV-negative patients. All 11 patients with serology positive for CBV 2, 3, and 5 had HLA-DR 4 and DQ IV patterns. This was significantly (P less than 0.01) different from all five CBV 4-positive patients, who in contrast all had HLA-DR 3 or HLA-DQ III patterns. CBV 1-positive patients (n = 2) all had HLA DR 3, 4, and HLA-DQ III, IV patterns. Thus CBV 4 seems to be significantly associated with a different host genetic constitution from at any rate CBV 2, 3, and 5, and possibly CBV 1. PMID- 2888189 TI - [Remarks on W. Koch's short communication "Incidence of narcosis in piglets"]. PMID- 2888190 TI - The tat gene of human T-lymphotropic virus type 1 induces mesenchymal tumors in transgenic mice. AB - Human T-lymphotropic virus type 1 (HTLV-1) is a suspected causative agent of adult T-cell leukemia. One of the viral genes encodes a protein (tat) that not only results in transactivation of viral gene expression but may also regulate the expression of certain cellular genes that are important for cell growth. Transgenic mice that expressed the authentic tat protein under the control of the HTLV-1 long terminal repeat were generated, and cell types that are permissive for the viral promoter and the effects of the tat gene on these cells were studied. Three of eight founder mice with high levels of expression of the transgene in muscle were bred and then analyzed. All developed soft tissue tumors at multiple sites between 13 to 17 weeks of age. This phenotype was transmitted to nine of nine offspring that inherited the tat gene and were available for analysis. The remaining five founders expressed the transgene in the thymus, as well as in muscle. This second group of mice all exhibited extensive thymic depletion and growth retardation; in all of these mice, death occurred between 3 to 6 weeks of age before tumors became macroscopically visible. The tat gene under the control of the HTLV-1 regulatory region showed tissue-specific expression and the tat protein efficiently induced mesenchymal tumors. The data establish tat as an oncogenic protein and HTLV-1 as a transforming virus. PMID- 2888191 TI - A transgenic mouse model for human neurofibromatosis. AB - Human T-lymphotropic virus type 1 (HTLV-1) has been associated with the neurologic disorder tropical spastic paraparesis and possibly with multiple sclerosis. The tat gene of HTLV-1 under control of its own long terminal repeat is capable of inducing tumors in transgenic mice. The morphologic and biologic properties of these tumors indicate their close resemblance to human neurofibromatosis (von Recklinghausen's disease), the most common single gene disorder to affect the nervous system. The high spontaneous incidence of this disease, together with the diverse clinical and pathologic features associated with it, suggests that environmental factors may account for some of the observed cases. Multiple tumors developed simultaneously in the transgenic tat mice at approximately 3 months of age, and the phenotype was successfully passed through three generations. The tumors arise from the nerve sheaths of peripheral nerves and are composed of perineural cells and fibroblasts. Tumor cells from these mice adapt easily to propagation in culture and continue to express the tat protein in significant amounts. When transplanted into nude mice, these cultured cells efficiently induce tumors. Evidence of HTLV-1 infection in patients with neural and other soft tissue tumors is needed in order to establish a link between infection by this human retrovirus and von Recklinghausen's disease and other nonlymphoid tumors. PMID- 2888192 TI - Synthetic peptide immunoassay distinguishes HIV type 1 and HIV type 2 infections. AB - Efforts to solve the epidemiologic puzzle of AIDS in Africa are complicated by the presence of multiple human retroviruses. Simple serologic tests that unambiguously distinguish among infections by these retroviruses are essential. To that end, a partially conserved immunoreactive epitope was identified in the transmembrane glycoproteins of human immunodeficiency viruses (HIV) types 1 and 2. Synthetic peptides derived from these conserved domains were used in sensitive and specific immunoassays that detect antibodies in sera from patients infected with HIV-1 or HIV-2. By making single amino acid substitutions in the HIV-1 peptide, it was possible to demonstrate HIV-1 strain-specific antibody responses to this epitope. Such custom-designed peptides synthesized from this domain are likely to detect newly discovered HIV types, define infection with specific HIV strains, and allow detection of group-common antibodies. PMID- 2888193 TI - Gastrinoma: the Zollinger-Ellison syndrome. PMID- 2888194 TI - Insulinoma and glucagonoma. PMID- 2888195 TI - Medullary carcinoma of the thyroid gland. PMID- 2888196 TI - Case report 429: Adult T-cell leukemia (ATL). PMID- 2888198 TI - Pancreatic pseudocysts. PMID- 2888197 TI - Prescription drug abuse and dependence in clinical practice. PMID- 2888199 TI - [Treatment of hemorrhagic fever with a renal syndrome]. PMID- 2888200 TI - Evaluation of maternal and developmental toxicity. Proceedings of the consensus workshop. Rockville, Maryland, May 12-14, 1986. PMID- 2888201 TI - Problems facing the decision-maker in the risk assessment process. AB - This paper presents an overview of the U.S. Environmental Protection Agency's risk assessment process, describes problems that the Agency faces in conducting risk assessment, in general, and identifies some specific problems that the Agency confronts when conducting risk assessments on suspected developmental toxicants. As noted by the NAS (National Research Council: "Risk Assessment in the Federal Government: Managing the Process." Washington, DC: National Academy Press, 1983, pp 17-83), improving the quality and comprehensiveness of knowledge is the most effective way to improve risk assessment, but some limitations are inherent and may remain unresolvable. Therefore, inferences will always be required. The Agency's challenge is to ensure that these inferences are as soundly based as possible. PMID- 2888203 TI - Maternal factors in developmental toxicity. AB - The maternal organism provides the developing embryo with its physical environment, nutrients, and a mechanism for eliminating metabolic wastes. Since the physiological state of the pregnant female affects her ability to provide those requirements for the developing embryo, it is not surprising that there are maternal factors that can affect the wellbeing of the embryo. Extremes of maternal age in both humans and animals have been implicated in growth retardation, as well as autosomal trisomies. The influence of maternal size on fetal size is more pronounced among larger species with longer gestation periods such as humans and domestic animals. A clear relationship between the parity of the mother and potential developmental toxicity in humans has not been established due to the confounding influences of maternal age. Among laboratory rodents, however, it appears that offspring of multiparous animals are at increased risk of developmental toxicity. A variety of infectious agents, particularly viruses, have either been demonstrated or implicated as causes of developmental toxicity. In addition, hyperthermia is a possible confounding factor inherent with maternal infection. Although under experimental conditions hyperthermia is teratogenic in laboratory animals, a causative role for transient hyperthermia, which occurs during febrile states concomitant with infections, cannot be clearly established. Chronic maternal vascular disease states including essential hypertension, heart disease, or diabetes mellitus are likely to contribute to uteroplacental insufficiency and developmental toxicity. Poor maternal nutrition among humans contributes to growth retardation, but not to malformations. The production of "abnormal" maternal antibodies, such as are present in Rh incompatibility, can cause fetal wastage. An important maternal factor in humans is uteroplacental insufficiency, which can occur in normal states like twinning, as well as in abnormal conditions including reduced placental size, chronic maternal hypoxia, or uterine ischemia. Although all these maternal factors can contribute to developmental toxicity, they do not necessarily occur as isolated events. Some developmental toxicants exert deleterious effects within both the embryo and the maternal system. PMID- 2888202 TI - Assessment of adult toxicity in developmental versus prechronic toxicology studies. AB - There is no general agreement at the present time regarding the role of maternal toxicity in the manifestation of teratogenic effects or developmental toxicity animal studies designed to identify the teratogenic potential of chemicals. A survey of 90 teratology studies published in the recent literature revealed wide differences in the amount and nature of maternal toxicity data collected in teratology studies. In addition, the use of the maternal toxicity data in the process of interpreting developmental toxicity varied widely between authors. In comparison with teratology studies, there is more uniformity in the collection of toxicity data in prechronic toxicity studies. The guidance provided by various government agencies on the parameters to be observed in prechronic toxicity studies is much more explicit than that provided regarding the collection of maternal toxicity data in teratology studies. Because of the likely importance of maternal toxicity in the conduct and interpretation of teratology studies, it is recommended that more maternal toxicity data be collected in teratology studies and the parameters be standardized between laboratories so that data are comparable. Guidelines should be established for the use of maternal toxicity data in the interpretation of the results of teratology studies. PMID- 2888204 TI - The potential relationship of maternal toxicity, general stress, and fetal outcome. AB - Standard teratology bioassays generally call for a top dose level which is sufficient to induce some form of overt maternal toxicity such as death or weight loss. The presence of such maternal toxicity is often a confound in the interpretation of experimental results, especially at those dose levels producing the toxicity. While the physiological bases for the toxicity vary widely in a compound-related fashion, one underlying factor that remains constant for most induced toxicity is the presence of generalized stress in the affected animals. Previous studies have indicated that pregnant animals treated acutely with toxic levels of a variety of pharmacologically unrelated chemicals produced litters without a recognizable syndrome of defects, except for an increased incidence of supernumerary ribs (SNR). The present study reports on the effects of immobilization stress on the production of SNR in the Sprague-Dawley rat and the CD-1 mouse. Pregnant animals were immobilized in the supine position for 12-hour periods during the day of greatest sensitivity to SNR production (days 9 and 10 in the mouse and rat, respectively). Animals were killed immediately before term and the fetuses were examined. An increase in SNR was noted in immobilized mice but not rats. These results suggest that such fetal effects may be the result of general agent-induced maternal stress. PMID- 2888205 TI - Approaches to defining the relationship of maternal and developmental toxicity. AB - Maternal and developmental toxicities reported in the literature were examined in an attempt to define more clearly their relationship. Relationships were difficult to ascertain because maternal toxicity end points are not clearly defined, or even assessed, in every study. However, maternal toxicity accompanied by developmental toxicity is the most common outcome of in vivo testing. Approaches to define these associations have included assessment of acute maternal toxicity and teratogenicity; evaluation of maternal toxicity and its association to developmental toxicity in general, and to malformations, specifically; and examination of developmental variations, embryolethality, and altered growth. None has demonstrated an unequivocal relationship between specific maternal and developmental toxicities: Developmental disruption appears not to result unconditionally from maternal toxicity. Maternal "stress" appears to have some impact on development but resists further definition at this time. Variations in association may be due to the extent to which maternal homeostasis has been compromised. Several quantitative approaches to relating maternal toxicity and developmental toxicity in animal systems (ie, relative teratogenic index, adult/developmental toxicity ratio) may provide the most satisfactory means of evaluating developmental toxicity testing for assessment of hazard. PMID- 2888206 TI - Use of the adult developmental relationship in prescreening for developmental hazards. AB - The overwhelming majority of chemicals already in commerce or brought into use each year have not been evaluated for their potential to adversely affect in utero development. Data from those that have been evaluated thus far in pregnant laboratory animals establish that most, but not all, were no more hazardous to the conceptus than they were to adult homeostasis. Most did not need standard developmental toxicity testing because avoidance of adult toxic exposure levels would have precluded abnormal in utero development. The six general principles of teratology when modified, expanded, and placed into this type of context of contemporary developmental toxicology allow an updating of the present testing sequence which was devised prior to 1966. The developmental hazard index (A/D ratio) calculated from the adult and developmental NOELs of standard Segment II evaluations is predicted by in vitro means. This determination, when coupled with adequate considerations of exposure can be used to prioritize chemicals for more elaborate developmental toxicity tests. Those chemicals with large ratios, i.e., disruptive of embryogenesis at treatment levels too low to produce overt effects in the mother and/or with significant concern regarding exposure, can be identified and tested in pregnant laboratory animals as high priority items. Those with low ratios and those for which there is a low level of concern regarding exposure potential also can be identified and are not high priority items for testing in pregnant animals. The proposed tier system establishes priorities of testing based on exposure and the concept of target organ toxicity applied to the embryo. It provides intensive in vivo evaluations of those chemicals for which developmental effects testing is most needed and avoids use of resources and animals for unnecessary testing of agents that do not pose threats to the conceptus. PMID- 2888207 TI - Maternal toxicity in humans and animals: effects on fetal development and criteria for detection. AB - Evaluation of published human and animal teratology data revealed associations between maternal toxicity and congenital malformations and embryofetal death. This has been reported elsewhere in detail and is herein summarized. Regarding human data, intrauterine deaths were observed to occur in association with 1) maternal homeostatic changes due to phenylketonuria and diabetes and 2) maternal toxicity resulting from alcohol abuse, use of aminopterin, and, possibly, trimethadione. A pattern of malformations that was similar and thus suggestive of a common cause was noticed among malformations attributed to phenylketonuria, diabetes mellitus, aminopterin, alcohol, warfarin, phenytoin, phenobarbital, trimethadione, and valproic acid. On reviewing 234 studies of agents tested in hamsters, mice, rats and rabbits, a fairly strong association between maternal toxicity and embryo-fetal mortality was observed. Further, a consistent pattern of fetal malformations associated with maternotoxic effects was discovered in a survey of 476 studies of agents tested in these four species. In these reviews, it was postulated that maternal toxicity per se could possibly cause such fetal effects. For evaluating maternotoxic effects in experimental studies, the minimum maternal data required would be frequent measurements of maternal body weight and food consumption, signs of altered behavior, death, and gross lesions at necropsy. PMID- 2888208 TI - Comparison of maternal and fetal toxic dose responses in mammals. AB - The role of maternal toxicity in adverse developmental outcome and the importance of maternal toxicity as a factor in developmental risk assessment have received increasing attention in the recent literature. This paper reviews these concepts and some of the experimental approaches that have been used to assess their importance. The often non-parallel nature of maternal and fetal toxic dose response curves makes specific comparisons of maternal and fetal toxic doses quite difficult. The use of specific ratios of maternal to fetal toxic doses, such as the A/D ratio and the Relative Teratogenic Index is discussed, including some of the difficulties encountered in assigning such ratios, and a compilation of A/D ratios for compounds for which this ratio could be estimated in more than one mammalian species is included. Results of our studies on the fungicide, dinocap, for which the A/D ratio does not seem to be consistent across species, are briefly reviewed. Maternal toxicity is usually evaluated only on the basis of significant mortality, dose-related weight loss, or obvious external observations. Some examples of other more specific indications of maternal toxicity that may be involved in teratogenesis are presented. PMID- 2888209 TI - Consensus workshop on the evaluation of maternal and developmental toxicity work group I report: end points of maternal and developmental toxicity. AB - It was concluded that this conference, sponsored by the EPA, has provided an opportunity to state current ideas regarding the utility of data from studies in developmental toxicology and that the deliberations have highlighted the need to consider fundamental relationships between maternal and developmental effects in a more comprehensive manner in the future. PMID- 2888210 TI - Consensus workshop on the evaluation of maternal and developmental toxicity work group II report: study design considerations. PMID- 2888211 TI - Consensus workshop on the evaluation of maternal and developmental toxicity work group III report: low dose extrapolation and other considerations for risk assessment--models and applications. PMID- 2888212 TI - Implications of the consensus workshop on the evaluation of maternal and developmental toxicity. PMID- 2888213 TI - Developmental toxicity of dinocap in the mouse is not due to two isomers of the major active ingredients. AB - Technical-grade dinocap, a complex-mixture fungicide, is teratogenic in the CD-1 mouse, causing cleft palate and otolith defects. In this study we compared the developmental toxicities of 2,4-dinitro-6-(1-methylheptyl)phenyl crotonate and 2,6-dinitro-4-(1-methylheptyl)phenyl crotonate, model isomers of the major active ingredients of technical dinocap, to the known teratogenicity of the technical compound. Individual isomers, both isomers combined, or technical dinocap were administered to pregnant mice on days 7-16 of gestation. Some dams were killed at term and litters were removed, dead fetuses and resorptions were counted, and live fetuses were weighed and preserved in Bodian's fixative for examination for cleft palate. Other treated dams were allowed to give birth: postnatal viability and growth, development of swimming behavior, and otolith formation were evaluated. As in previous studies, technical-grade dinocap caused cleft palate and weight deficits in fetuses at term and increased neonatal mortality and abnormal swimming behavior, torticollis, and deficient otolith formation in surviving pups. Neither of the purified isomers exhibited any developmental toxicity when administered under identical conditions. Thus, it is concluded that these isomers are not the active teratogenic component(s) in technical-grade dinocap. PMID- 2888214 TI - Effect of prenatal reserpine exposure on development of the postnatal rat heart. AB - Previous studies have suggested that reserpine treatment may result in altered heart development. In order to more fully investigate this possibility, reserpine was administered s.c. at 0, 0.375, or 0.75 mg/kg/day to pregnant rats on gestation days 12-15. Maternal weight gain, as well as pup weight on postnatal day (PND) 1, was significantly reduced in a dose-dependent manner. Litter size was unaffected, but reserpine-treated dams had more dead pups than did control dams. On PND 1, litters were randomly standardized at ten pups each for analysis on PNDs 5, 8, 15, and 22. Pup body weight and heart weight were reduced in a dose related manner at all ages measured. The decreased heart weights were probably due to decreases in cell number. Beta-adrenergic receptor concentration was significantly reduced only on PND 5, at the low reserpine dose, and was not considered to be a treatment effect. Prenatal reserpine exposure had no effect on levels of basal cardiac ornithine decarboxylase (ODC), an enzyme associated with growth and development. Cardiac ODC stimulation by insulin and isoproterenol also showed no effects of maternal reserpine treatment. The results suggest that maternal reserpine treatment may lead to adverse effects in the developing offspring. PMID- 2888215 TI - Benomyl-induced craniocerebral anomalies in fetuses of adequately nourished and protein-deprived rats. AB - Benomyl, a benzimidazole fungicide, produced craniocerebral and systemic malformations in fetal rats when administered by gavage in doses of 31.2, 62.5, and 125 mg/kg of maternal body weight on days 7-21 of gestation. Malformations increased in incidence and severity with increasing benomyl dosage and nearly doubled when coupled with a protein-deficient diet. Protein deficiency alone produced only decreased fetal weight. High benomyl doses produced higher percentages of fetal resorptions and late fetal deaths, and these percentages also increased with protein deficiency. A benomyl dose of 62.5 mg/kg in protein deficiency dams, the optimal combination for a high incidence of anomalies and low fetal wastage, produced hydrocephalus in 69.4% of fetuses, meningocele in 8.2%, encephalocele in 14.3%, exencephaly in 44.9%, anencephaly in 14.3%, corpus callosum agenesis in 26.5%, periventricular necrosis in 26.5%, and periventricular cellular "overgrowth" in 55.1%. The most common combination of anomalies was hydrocephalus, exencephaly, and periventricular "overgrowth." Common systemic malformations included cleft palate, micromelia, hydroureter, and misshapen tails. No fetus was entirely normal at the highest benomyl dose. Benomyl has been shown by others to bind tubulin and inhibit the formation of microtubules that are important in neurulation, mitosis, and cell migration during early brain development. Thus, it is suggested that benomyl, coupled with a protein-deficient diet, offers a teratogenic model with a spectrum of abnormalities similar to hypervitaminosis A but with a higher yield of specific craniocerebral anomalies. PMID- 2888216 TI - Mullerian remnants of male mice exposed prenatally to diethylstilbestrol. AB - Prenatal exposure of males to diethylstilbestrol (DES) results in reproductive tract teratogenesis, ie, retention of Mullerian duct remnants. The potential of these remnants to develop pathological changes has not been studied. Therefore, pregnant outbred CD-1 mice were subcutaneously injected with daily doses of DES (100 micrograms/kg) on days 9 through 16 of gestation. DES-exposed male offspring and age-matched control male mice were sacrificed at 10 to 18 mo of age and examined for reproductive tract abnormalities. Prominent Mullerian remnants were observed in 268 out of 277 (97%) of the DES-exposed male mice. These remnants differentiated into "femalelike structures" homologous to oviduct and uterus. The Mullerian remnants were often enlarged and cystic and shared supporting connective tissue with adjacent male structures. Previously reported lesions, termed "epididymal cysts," were determined histologically to be cystic "oviductlike" structures and were, therefore, considered a Mullerian duct abnormality. Pathological changes in these male oviductal and uterine homologs included benign and malignant lesions. In addition, epididymal structures were altered. Inflammation and sperm granulomas were prevalent in DES-treated mice as young as 10 mo old but were only observed in control mice at 18 mos. Cysts of epididymal duct origin, hyperplasia, and adenoma of the epididymal duct were also observed. No comparable abnormalities were noted in 122 control males of corresponding ages. The data presented in this report demonstrated that transplacental exposure to DES affected the differentiation and normal development of the male genital tract involving both the Mullerian (paramesonephric) and Wolffian (mesonephric) ducts. The long-term changes in these tissues include lesions, some of which resembled neoplasia although the natural history of the lesions is not known. Moreover, some previously described abnormalities referred to as "epididymal cysts" were associated with tissues derived from embryonic female origin. PMID- 2888217 TI - Investigation of the teratogenic effects of exercise on pregnancy outcome in mice. AB - Swiss Webster female mice were arbitrarily assigned to a heavily exercised group (HE), a moderately exercised group (ME), or a sedentary group (S). Exercised groups were subjected to a progressive treadmill training routine, 6 days a week (60 min per day) for a total of 9 wk. Following mating after 6 wk of training, treatment groups continued to exercise at preconceptual intensities. Pregnant mice were sacrificed on the 19th day of pregnancy, and the fetuses were recovered. A positive training effect was demonstrated by a significant increase in succinate dehydrogenase activity in the gastrocnemius muscles of exercising dams. The numbers of implants, resorptions, live fetuses, mean fetal weight, and developmental stage were unaffected by the exercise treatment. A detailed fetal examination revealed no significant skeletal or gross tissue abnormalities in any of the experimental groups. PMID- 2888219 TI - Agent Orange and risks to reproduction: the limits of epidemiology. PMID- 2888218 TI - Cyclophosphamide: interstrain differences in the production of mutagenic metabolites by S9-fractions from liver and kidney in different mutagenicity test systems in vitro and in the teratogenic response in vivo between CBA and C 57 BL mice. AB - The formation of mutagenic compounds from cyclophosphamide (CPA) by S9-fractions from liver (S9L) or kidney (S9K) of pregnant CBA and C 57 BL mice was investigated, using point mutations in Salmonella typhimurium (TA 1535) and the induction of sister chromatid exchanges (SCE) in human peripheral lymphocytes (HPL) or Chinese hamster ovary (CHO) cells as end points. In addition, the teratological response of CBA and C 57 BL mice to CPA on day 11 of pregnancy was analysed in vivo. The results are as follows: (1) S9L from CBA mice was more effective than S9L from C 57 BL mice in metabolizing CPA to products inducing mutations in Salmonella and SCEs in HPL and CHO cells. (2) S9L was more effective than S9K from both strains of mice. (3) In vivo pretreatment of mice with a single dose of CPA (20 mg/kg) reduced the in vitro metabolizing capacity of S9L and S9K significantly and led to the disappearance of the interstrain difference. (4) The embryolethal and teratogenic effects of CPA were stronger in C 57 BL than in CBA mice; the types of teratological effects were partially different in the two strains. PMID- 2888220 TI - Venomous pelagic coelenterates: chemistry, toxicology, immunology and treatment of their stings. AB - Ten years have elapsed since our last review article on the toxicology of venomous pelagic coelenterates was published (Burnett and Calton, 1977). Investigation on important medusae and the chemistry of their nematocyst venoms have been expanding. The venomous jellyfish discussed here include the Portuguese man-o'war, (Physalia physalis), the sea nettle (Chrysaora quinquecirrha), the box jellyfish (Chironex fleckeri and/or Chiropsalmus quadrigatus), the cabbage head jellyfish (Stomolophus meleagris), the lion's mane jellyfish (Cyanea capillata), the Irukandji jellyfish (Carukia barnesi), the Moreton Bay Carybdeid medusa (Morbakka), and the mauve blubber (Pelagia noctiluca). PMID- 2888221 TI - Effects of equinatoxin on the guinea-pig atrium. AB - Equinatoxin is a lethal protein isolated from a sea anemone, Actinia equina. The toxin (0.1-3 micrograms/ml) caused an initial inhibition followed by an augmentation of contractions and beating rates in the isolated guinea-pig atrium. The inhibitory phase was transient (30-60 sec), while the stimulant phase lasted for about 30 min. The treated atrium showed tachyphylaxis to the toxin. The inhibitory effect of the toxin was diminished by tetrodotoxin and atropine and abolished by 8-phenyltheophylline or mepacrine. Dipyridamole, which blocks the uptake of adenosine in the heart, enhanced the inhibitory effect. The stimulant effect of the toxin was inhibited by indomethacin or mepacrine and abolished by a combination of both, but was not inhibited by propranolol. Bioluminescent assay performed during the inhibitory phase showed an increased release of ATP and radioimmunoassay during the stimulant phase revealed an increased release of prostaglandin E2 from the treated atrium. These results suggest that the cardiac inhibitory effect of equinatoxin is mainly due to release of adenyl compounds, while the cardiac stimulant effect of the toxin may result from the liberation of arachidonic acid and subsequent formation of prostaglandins in the guinea-pig atrium. PMID- 2888223 TI - Inhibition of hybrid resistance by 5-fluorouracil. Destruction of a Thy-1+ Lyt 1+2- spleen cell implicated in the expression of hybrid resistance. AB - Hybrid resistance designates the poor proliferation of parent-strain bone marrow cells injected into lethally irradiated hybrids. While testing a variety of oncostatic drugs for their capacity to inhibit hybrid resistance, we found that 5 fluorouracil (5-FU) injected into B6D2F1 hybrids three days before grafting enhances the growth of parent-strain B6 bone marrow cells. Hybrid resistance can be restored in these 5-FU-treated B6D2F1 recipients by the injection of spleen cells from untreated (normal) B6D2F1 mice. Treatment of these normal B6D2F1 spleen cells with anti-Thy-1 or anti-Lyt-1 antibodies plus complement abolishes their capacity to restore resistance, whereas treatment with anti Lyt-2 antibody plus complement has no effect. It is known that the rejection of parent-strain bone marrow cells by the F1 hybrid is a multistep process in which more than one cell type is involved, and that the final effector cell is asialo-GMI+, cyclophosphamide-sensitive, and responsive to IFN (possibly the natural killer cell). The Thy-1+Lyt-1+2- spleen cell we describe here, which is eliminated by the 5-FU, doesn't seem to be the final effector cell for hybrid resistance since transfer of spleen cells from cyclophosphamide-treated (final-effector-cell depleted) B6D2F1 hybrids into 5-FU treated B6D2F1 mice restores hybrid resistance just as well as do normal B6D2F1 spleen cells; and, when injected into 5-FU treated B6D2F1 hybrids, the IFN inducer pI:pC also restores resistance. The cell we now describe would be a third cell type, probably responsible for the initial recognition of grafted parent-strain bone marrow cells, which triggers the mechanism of hybrid resistance. This hypothesis could explain the observed specificity of parent-strain bone marrow graft rejection by F1 hybrids. PMID- 2888222 TI - Estimating the risks of transfusion-associated acquired immune deficiency syndrome and human immunodeficiency virus infection. AB - The risk of transfusion-associated acquired immunodeficiency syndrome (AIDS) has been difficult to estimate because of the long and variable incubation period. Mathematical modeling suggests there may eventually be 2100 cases among persons aged 13 to 65 who received transfusions between 1978 and 1984. An estimated 12,000 living transfusion recipients of all ages from these years are infected with the human immunodeficiency virus, the virus that causes AIDS. Secondary transmission might be prevented by testing and counseling recipients, but the likelihood of infection in any single recipient is small. PMID- 2888224 TI - Specific and nonspecific resistance to local graft-versus-host reaction in F1 hybrids pretreated intravenously with parent-strain spleen cells. I. Two distinct mechanisms. AB - B6D2F1 hybrid mice pretreated i.v. with 5 X 10(7) spleen cells from B6 donors seven days earlier (B6-pretreated B6D2F1 hybrids) develop resistance to local GVHR induced by the subcutaneous injection of spleen cells of either B6 (GVHR-B6) or D2 (GVHR-D2) origin. This resistance has specific and a nonspecific components that concern the GVHR-B6 and the GVHR-D2, respectively. The two types of resistance to GVHR are neither induced under the same conditions nor mediated by the same mechanism. Specific resistance to GVHR is observed in B6D2F1 hybrids pretreated with unseparated, anti-Lyt-1.2+C' treated or 1000 rads-irradiated B6 cells, but not in B6D2F1 hybrids pretreated with anti-Thy-1.2+C' or anti Lyt 2.2+C'-treated B6 cells. In contrast, nonspecific resistance to GVHR is induced only by pretreatment with unseparated B6 cells. Treatment of B6 cells with anti Thy-1.2, anti-Lyt-1.2, or anti-Lyt-2.2 moAb plus C', or their irradiation at 1000 rads completely abolishes their capacity to induce the nonspecific resistance to GVHR. Moreover, specific resistance to GVHR can be transferred to normal B6D2F1 mice by injection of nylon-adherent, anti-Thy-1.2+C'-treated or 2000-rads irradiated, but not unseparated or nylon-nonadherent, B6-pretreated B6D2F1 spleen cells. Treatment of nylon-adherent B6-pretreated B6D2F1 cells with anti H-2d antiserum plus C' does not affect their capacity to transfer specific resistance to GVHR. Nonspecific resistance to GVHR can be transferred by unseparated, anti Lyt-1.1+C' or anti Lyt-2.1+C'-treated, but not by anti-Thy-1.2+C' anti-Lyt 1.2+C', anti-Lyt-2.2+C'-treated or 2000-rads-irradiated B6-pretreated B6D2F1 spleen cells. Both types of resistance are observed in B6D2F1 hybrids pretreated with more than 2.5 X 10(7) B6 spleen cells. PMID- 2888225 TI - [Species and organ differences in the activity and regulation of adenylate and guanylate cyclases]. AB - The activity of adenylate and guanylate cyclases was determined in adrenal, heart, liver and fat tissues of guinea pigs, mice, rabbits and monkeys. The enzymes activities varied markedly depending both on the species and organs. The highest basal activities of adenylate cyclase was observed in all organs of guinea pigs. It was found that organs with low basal level of adenylate cyclase possess high guanylate cyclase. Species variations of the basal and stimulated adenylate cyclase activity may determine the functional activity of an organ: the higher the adenylate cyclase activity, the more intensive steroidogenesis in adrenals, lipolysis in the fat tissue, muscle contraction and nerve impulse conduction in heart. PMID- 2888226 TI - Survey: localization and operation for nonpalpable testes. PMID- 2888227 TI - Bovine monoclonal antibodies to the F5 (K99) pilus antigen of E. coli, produced by murine/bovine hybridomas. AB - Lymph node cells from calves immunized with purified pilus antigen of K99+ enterotoxigenic E. coli (ETEC) were fused with mouse myeloma (NSO) cells, and with non-Ig producing mouse/calf hybridomas or with a bovine Ig-producing mouse/calf/calf secondary hybridoma. Lines secreting bovine monoclonal IgG1 specific for K99 pilus antigen in an ELISA were obtained in each case. The two lines derived from xenohybridoma fusion partners have been secreting anti-K99 bovine monoclonal antibody for over one year in continual passage. None of the antibodies cross-reacted with other pilus types including K88, CFAI, CFAII, 987P or CP; they all inhibited agglutination of horse RBC (which have a K99 receptor) in the presence of K99 antigen; they showed positive fluorescence in an indirect binding assay on K99+ ETEC and inhibited K99+ ETEC adhesion to piglet enterocytes. These antibodies have potential prophylactic and therapeutic use in control and treatment of diarrhoea. PMID- 2888229 TI - Hexamethonium: a probe to assess autonomic nervous system involvement in upper gastrointestinal functions in conscious sheep. AB - Hexamethonium, which inhibits cholinergic transmission by preventing acetylcholine release, has been considered an ideal reference drug for the blockade of autonomic ganglia, Auerbach plexus and reflex gastrointestinal secretions. The degree of inhibition of ruminant gastrointestinal functions with this reference drug were as follows: cyclical contractions of the reticulo-rumen and abomasal motility greater than gastric acid secretion and duodenal migrating myoelectrical complexes. Although reduced at high dosages, the initiation of migrating myoelectric complexes was enhanced at clinically used dosages. The duration of the inhibition of reticular contractions was dose-related varying from 0.5 to 5 h for 1.25 to 20 mg/kg subcutaneously. Abomasal motility and acid secretion were similarly reduced but exhibited strong and long-lasting rebound effects. Inhibition of the reticulum by the blockade of muscarinic receptors by atropine was also dose-related lasting from 0.5 to 3 h for 0.5 to 2 mg/kg, whereas inhibition of the abomasal motor and secretory functions lasted from 1 to 6 h. These results suggest a higher degree of impingement of the parasympathetic pathways on abomasal acid secretion and motility than on the cyclical activity of the reticulum and only a modulatory role of the extrinsic neural activity on the cyclical motor events of the duodenum. PMID- 2888228 TI - Normal serum activities of some diagnostic enzymes in dromedary camel in Sudan. AB - 76 adult camel (30 males and 46 females) sera were surveyed for the normal activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine phospho-kinase (CPK), gamma-glutamyl transpeptidase (GGT) and lactate dehydrogenase (LDH). The values recorded for the above enzymes were compared to other data in the literature. PMID- 2888230 TI - Comparison of CEA distribution in lesions and tumors of salivary glands as determined with monoclonal and polyclonal antibodies. AB - Immunohistochemical localization of carcinoembryonic antigen (CEA) with conventional antibody to CEA (anti-CEA), nonspecific crossreacting antigen (NCA) absorbed polyclonal antibody to CEA (NCAa-CEA), and monoclonal antibody to CEA (Mono-CEA) have been compared in obstructive lesions and salivary gland tumors. Normal salivary glands gave strong staining of the luminal borders of acinar cells with anti-CEA, whereas no staining occurred with Mono-CEA. Obstructive lesions showed occasionally marked staining with anti-CEA in some acinar cells, but there was no reaction with Mono-CEA. Of 69 pleomorphic adenomas examined, 34 were positively stained with anti-CEA, 18 with NCAa-CEA and 8 with Mono-CEA along the luminal borders of the tumor cells. The frequency of positive staining of material within tubular lumina was similar with all three immunoreagents. Neoplastic cells were positive with Mono-CEA in only three cases, while eight cases were positive with NCAa-CEA and 11 cases with anti-CEA. In salivary gland tumors true CEA is be found mainly at the border of tumor cells, but the frequency of positive reactions is low. PMID- 2888231 TI - An improved DAPI-DNA cytofluorometry by hypotonic cytolysis. Its application to tumor cell heterogeneity. AB - The effect of cell cytolysis on DAPI-DNA cytofluorometry was studied in order to eliminate nonspecific cytoplasmic hindrances in DAPI staining. A great improvement in the reproducibility of DNA determination was attained when cells were treated with hypotonic KCl (0.075 M) solution. The DNA content per cell of the mgC5 clonal line (normal diploid cell containing 2C DNA units) after hypotonic treatment was 3.07 +/- 0.06, while that of mgC5 cells without hypotonic treatment was 3.50 +/- 0.26, indicating a remarkable decrease from 7.4% to 2.0% in the coefficient of variation. In detecting tumor cell heterogeneity, our cytolytic method was superior to the method of counting the mode of chromosome number. The modal chromosome numbers of nontumorigenic m and its derivatives, mgC4 and mgC5, were 69, 68 and 67 respectively, while those of their tumorigenic counterparts, magc, mgC4V1 and mgC5V1 were 68, 66 and 67. The DNA contents of nontumorigenic m, mgC4 and mgC5 were 3.00 +/- 0.10 (mean +/- SD), 3.07 +/- 0.06 and 3.07 +/- 0.12, while those of their tumorigenic counterparts, magc, mgC4V1 and mgC5V1 were 3.67 +/- 0.15, 3.23 +/- 0.06, 3.27 +/- 0.06 respectively. A statistically significant difference in DNA content between the tumorigenic and nontumorigenic cells was observed at least at the p less than 0.05 level (t-test) when DNA content was employed for comparison, but not when the modal chromosome number was employed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888232 TI - Immunohistochemical evaluation of ras oncogene expression in pulmonary and pleural neoplasms. AB - We undertook an immunohistochemical analysis of human bronchopulmonary epithelial neoplasms and pleural mesotheliomas using a monoclonal antibody which recognizes ras oncogene products (p21ras). The monoclonal antibody, RAP-5, recognizes both unaltered and certain mutated p21ras. Formalin fixed and paraffin embedded tissue samples of 187 lung epithelial tumors and 27 pleural mesotheliomas were investigated; normal and bronchiectatic lungs were similarly studied. Normal lung and pleural tissue did not immunostain except for occasional type II pneumocytes. Reactive type II pneumocytes adjacent to carcinomas and bronchiectasis immunostained consistently. Twenty four/34 (71%) squamous carcinomas immunostained. Only 8/50 (16%) adenocarcinomas immunostained focally and weakly whereas 19/24 (79%) bronchioloalveolar carcinomas immunostained. Eleven/18 (61%) large cell carcinomas immunostained with variable intensity. Eleven/13 (85%) carcinoids, 6/7 (85%) well differentiated neuroendocrine carcinomas, and 18/21 (86%) intermediate cell neuroendocrine carcinomas immunostained while none of 20 small cell neuroendocrine carcinomas immunostained. Only a few mesotheliomas were immunostained focally. Two/14 (14%) epithelial type and 1/9 (11%) biphasic type mesotheliomas immunostained weakly; none of 4 spindle cell mesotheliomas immunostained. We conclude that while at least occasional cases of most types of pulmonary epithelial neoplasms express p21ras, the frequency and intensity of the expression are distinctly greater in certain tumor types such as squamous, bronchioloalveolar, and neuroendocrine neoplasm except for the small cell type. Contrary to these lung epithelial neoplasms, most mesotheliomas did not immunostain for p21ras. Whether the enhanced p21ras expression may point to a different mechanism of transformation or may merely reflect differentiation features remains undetermined. PMID- 2888233 TI - Induction of granulopoiesis of mastocytoma cells: ultrastructural and cytochemical studies on production of serotonin in a cultured mouse mastocytoma cell line. AB - Electron microscopic observations of an originally established mouse mastocytoma cell line (BSP-MST-2) revealed that the cytoplasm of many of the MST-2 cells contained small and low osmiophilic granules and a few mature electron-dense granules. Fluorescent- and immuno-histochemical examinations also suggested the immaturity of granules as the cytoplasmic reaction for serotonin (5-HT) was weak. Induction of further maturation of granules was investigated by administration of various chemical agents. Among the chemicals examined, sodium butyrate and hydrocortisone were effective. In the presence of 1 mM sodium butyrate for 24 h, the cytoplasmic granules contained an abundant dense matrix. MST-2 cells incubated with hydrocortisone at 5 micrograms/ml for 24 h showed a somewhat different granulopoietic pattern from those incubated with sodium butyrate, including numerous electron-dense progranules. Fluorescent- and immuno histochemical studies showed increased reactions of cytoplasmic 5-HT of both butyrate- and hydrocortisone-treated MST-2 cells. The specificity of these morphological and cytochemical changes was confirmed by treatment with reserpine, a drug which depletes cellular 5-HT; electron-dense materials were virtually diminished and cytochemical reactions were significantly decreased. The mode of induced production of 5-HT in mastocytoma granules is discussed, in relation to mastocyte differentiation. PMID- 2888234 TI - Amine dependence of proliferative activity in two transplantable lines of mouse colonic carcinoma. AB - Serotonin, histamine and their antagonists have previously been shown to influence both the cell proliferation rate and the volumetric growth rate of colonic tumours. Of these earlier studies, those on cell proliferation could not distinguish between direct effects on tumour cells and indirect effects on the host, whereas those on the volumetric growth rate of tumours, whilst suggesting an outcome related to the individual properties of the tumour rather than the host, could not distinguish between influences on cell gain, cell loss or stromal changes. In an attempt to distinguish between these possibilities the current experiments on the mitotic rate in two lines of transplantable mouse colonic carcinoma were undertaken. One line of tumour proved to be sensitive to inhibition by a histamine H2 receptor antagonist and a dopamine D2 antagonist but resistant to serotonin antagonists; the inhibition by histamine antagonists was surmountable by co-administration of histamine. The other line proved to be highly sensitive to the inhibitory effects of serotonin antagonist and less so to antagonists of the other two amines and in this case the effect of serotonin antagonists was surmountable by serotonin. These results suggest that the variations between different colonic tumours in the response to amine antagonists is due to differences in the extent of inhibition of cell proliferation rather than differences in cell loss or stromal effects. Thus it appears likely that amine antagonists are able to directly interfere with the proliferation of some colonic tumour cells. PMID- 2888235 TI - Involution of hyperplastic goitre in the adult male rat. Tissue compartment process with early iodide effect: a stereological and biochemical study. AB - The morphological and functional changes during involution of hyperplastic goitre have been investigated in the adult male rat. Male wistar rats received an iodine deficient diet for 6 months and during the last 2 months received propylthiouracil (PTU, 0.15%). By the end of this treatment (day 0), a hyperplastic goitre was obtained. A normal iodine supply was then given and PTU withdrawn. During the first 8 days of iodine refeeding, the plasma thyrotropin (TSH) remained at a high level (ten times the control value), whereas the thyroid iodide content was low on day 0, markedly increased on day 1 and decreased on day 4. Plasma T3 and T4 levels remained unchanged for 4 days and only increased on day 8. The total thyroid protein concentration was low on day 0 and then increased rapidly on day 8 (by 34%). The volume density of colloid remained low and unchanged until day 8, when it started to increase. However, the thyroid epithelial cell volume and the volume density of capillaries were raised on day 0, decreased rapidly in the next 8 days and more slowly later on. The total number of thyroid epithelial cells was considerably raised in the hyperplastic gland. It did not vary until day 16, when it decreased slowly, reaching a plateau on day 45 above the control value. The present data show that involution of hyperplastic goitre in the rat is due essentially to a decrease in thyroid epithelial cell volume and to a reduction of the increased number of capillary blood vessels present. The decrease in the number of epithelial cells is only 16.5%, suggesting that the death of thyroid epithelial cells contributes little. Half the process of involution, which occurs from days 0 to 8, is controlled by the thyroid iodide concentration rather than TSH, indicating the involvement of a thyroid autoregulatory mechanism. It must be emphasized, however, that the discontinuous pattern of epithelial cell number during involution may indicate that some cells with larger nuclei and more rapid turnover disappear more quickly after iodine refeeding. PMID- 2888236 TI - Ultrastructural changes in the rat liver during Euro-Collins storage, compared with hypothermic in vitro ischemia. AB - The ultrastructural alterations in liver tissue induced by in vitro ischemia at 4 degrees C under conditions commonly used for transplantation (Euro-Collins perfused and stored liver tissue) have been compared with changes due to hypothermic in vitro ischemia in non-perfused liver. It was found that the process of cell deterioration in non-perfused liver occurred very slowly; signs of irreversible damage appeared in sinusoidal lining cells before hepatocytes (after 24 and 96 h, respectively). Liver perfused with, and stored in Euro Collins solution showed acceleration of the ischemical damage in both types of cell (irreversible damage to sinusoidal lining cells after 12 h and to hepatocytes after 52 h), compared with non-perfused liver. These findings indicate that the safe period for storage of rat liver in Euro-Collins before damage to the microcirculatory system is less than 12 h. It might also be questioned whether Euro-Collins treatment is the optimal procedure for tissue preservation before liver transplantation. PMID- 2888237 TI - Morphometric evaluation of the turnover of autophagic vacuoles after treatment with Triton X-100 and vinblastine in murine pancreatic acinar and seminal vesicle epithelial cells. AB - Large numbers of autophagic vacuoles were found in murine pancreatic acinar and seminal vesicle epithelial cells following the administration of Triton X-100 or vinblastine for 4 h. The autophagic vacuoles disappeared rapidly from the cells after the administration of cycloheximide to animals pretreated with Triton X 100. The decay in seminal vesicle cells appeared to follow first-order kinetics with an estimated t1/2 of 8.7 min. The regression in pancreatic cells was equally rapid and less than half the initial volume of autophagic vacuoles was found at the 12th min after cycloheximide injection. This time, the decay curve appeared to be linear rather than exponential. Our data, together with the work of others, support the view that the average half-life of autophagic vacuoles is a fairly constant parameter kept within the range of 6-9 min in various types of mouse and rat cell when the late steps of autophagocytosis (i.e. the fusion of autophagosomes and lysosomes and the degradation within lysosomes) are not affected. The regression of autophagic vacuoles was slow in mice pretreated with vinblastine (t1/2 of about 27-30 min) suggesting that this drug slows down the turnover of autophagic vacuoles. Morphometric evaluation of the regression of the autophagic vacuole compartment after cycloheximide treatment can be used as a tool to distinguish between treatments which elevate the amount of autophagic vacuoles within the cells by increasing the rate of sequestration from those which expand the autophagic vacuole compartment by causing accumulation of autophagic vacuoles as a result of blockade of the late steps of the autophagic process. PMID- 2888238 TI - [Justification for the differential use of amplitude-modulated pulse therapy in different clinical variants of lumbar osteochondrosis]. PMID- 2888239 TI - [Cholesterol esterase activity in the rat aorta and liver after stimulation and blockade of beta-adrenergic receptors]. AB - Activities of lysosomal and cytoplasmic cholesterol esterases and cholesterol content in rat blood serum, liver tissue and aorta were studied after administration of ephedrine and propranolol. The ephedrine-induced lipolytic effect was fully inhibited by propranolol. The correlation between stimulation of beta-adrenergic receptors and activation of lipolytic enzymes was found. PMID- 2888240 TI - [Effect of the biotope and the intensity of invasion on the activity of various oxidation-reduction enzymes in Entamoeba histolytica]. PMID- 2888241 TI - [Lipoprotein metabolism and beta receptor blockers]. AB - Including own results a survey is given of the side effects of beta-receptor blockers on the plasma lipoprotein metabolism. The formation of a from the coronary-preventive point of view unfavourable lipoprotein risk profile under influence of individual beta-receptor blockers, among others propranolol, seems to be connected with an inhibition of a key enzyme in the lipoprotein metabolism, the lecithin-cholesterol-acyl transferase. Talinolol does not show these side effects. It is recommended to control the triglyceride level and the HDL cholesterol before the induction and after the beginning of a therapy with beta receptor blockers and to use talinolol instead of propranolol in pre-existing dyslipoproteinaemia or in unfavourable changes during the treatment. PMID- 2888243 TI - [Mediator mechanisms of the stimulatory effect of the vagus nerves on the heart]. PMID- 2888242 TI - [Variations in sleep onset in monotone stimulation: a review of the literature on short day-time nap studies]. PMID- 2888244 TI - [The humoral link in the mechanism of formation of conditioned food refusal in the edible snail]. AB - Effect was studied of hemolymph of snails-donors with conditioned food refusal, on learning the same habit by snails-recipients. Facilitation was observed of the recipients' learning depending on the quantity of injected hemolymph and the type of conditioned stimulus. The hemolymph of pseudo-conditioned donors inhibited the learning of intact snails-recipients. The possibility is suggested of appearance in the hemolymph of conditioned snails of one or several chemical factors, capable to facilitate elaboration of the same conditioned reflex. PMID- 2888245 TI - [Current knowledge about the rehabilitation of chronic psychiatric patients]. AB - Our considerations are based upon a new concept of schizophrenia and upon our clinical experience which has been controlled in two catamnestic studies. The new concept contains the notion of vulnerability, saying that there is no specific process underlying mental illness but there is a variety of interacting organic and psychosocial factors causing a special vulnerability leading towards psychotic break down in situations of stress. An optimal treatment should therefore consist of preventing relapse and at the same time of a soft promoting of social learning; thus an optimal treatment is a rehabilitation. Clinical experience and catamnestic studies show that mentally ill patients can be reintegrated into occupation and independent living even after a long history of illness and hospitalization. But we also find a severe ongoing handicap concerning social relations and quality of life, a strong indicator for the fact that rehabilitation has to continue even after a successful reintegration. PMID- 2888246 TI - [Oxidative and respiratory properties of isolated human kidney mitochondria]. AB - The oxidative and respiratory properties of isolated human renal mitochondria are characterized on the basis of the respiratory rates under defined conditions (active and decoupled respiration as well as respiration in rest) with the help of the respiratory control index and the ADP/O quotient. In comparison to the renal mitochondria of the rats the balances for the substrates succinate and glutamate/malate are three- to fourfold smaller. PMID- 2888247 TI - [Characteristics of the biological properties of a cell-free pertussis preparation]. AB - The biological properties of Bordetella pertussis antigenic complex, obtained by a technologically simple method from the medium used for the cultivation of B. pertussis, were studied. The preparation was characterized by pronounced hemagglutinating activity, toxicity, histamine-sensitizing and leukocytosis stimulating activity and produced a cytopathogenic effect on the culture of Chinese hamster ovary cells. The detoxified preparations showed pronounced protective activity in experiments on the active and passive protection of mice. The ED50 of the preparation was 0.146 microgram of protein. In the proposed human immunization dose containing 10 micrograms of protein the detoxified preparation showed no hemagglutinating, leukocytosis-stimulating or histamine-sensitizing activity and proved to be nontoxic in the weight loss test on mice. PMID- 2888248 TI - [Psychotropic drug therapy using maintenance dosage pumps]. AB - The article deals with questions related to the use of paracorporal automatic drug-administering devices designed for the prolonged administration of psychotropic drugs. This is the first ever experience with the use of artificial systems for drug administration in psychiatry. The authors have developed a scheme of drug administration and determined the optimal rate of injection and daily doses. Possible complications and side effects associated with this method of treatment, as well as the methods for their prevention and control are described in detail. According to preliminary data the administration of psychotropic drugs with the help of automatic devices may contribute significantly to the improvement of social adaptation of patients with minor mental disturbances and make easier the provision of psychotherapy, in particular it may considerably simplify functional training of patients with phobic abnormalities. The method appears to be especially promising with regard to maintenance therapy. PMID- 2888249 TI - [Effect of neuroleptic therapy on the structure of an episode in acute alcoholic psychoses]. AB - Clinical examination of 106 patients with acute alcoholic psychoses has shown a definite effect of neuroleptic therapy with phenothiazine drugs on the pathomorphosis of psychotic attacks. It has been found that the main direction of the therapeutic pathomorphosis in the studied group is the appearance in the structure of attacks of the alternately changing main forms of alcoholic psychoses-delirium, verbal hallucinosis, and paranoid, as well as an increase in the number of patients with consciousness disturbances of delirious or delirious oneiric type by the end of the attack. Positive results of the use of eglonyl in the treatment of acute alcoholic hallucinosis are presented. PMID- 2888250 TI - Effects of H2-receptor antagonists on prolactin secretion: specificity and mediation of the response. AB - The effects on prolactin secretion of histamine H2-receptor antagonists infused intracerebroventricularly were studied in urethane anaesthetized male rats. A dose of 1.6 mumol cimetidine stimulated basal prolactin secretion and did not affect the histamine-induced release, whereas 0.4 mumol cimetidine inhibited basal and histamine-stimulated prolactin secretion. 0.1 mumol cimetidine had no effect. The more potent H2-receptor antagonist ranitidine at doses of 0.1, 0.4, 1.6 mumol had no effect on basal prolactin secretion, whereas 0.4 and 1.6 mumol inhibited the histamine-stimulated secretion completely. SKF-92408, a compound resembling cimetidine in chemical structure but devoid of H2-receptor antagonist activity, stimulated basal prolactin secretion at a dose of 1.6 mumol, but had no effect on the histamine-induced release or at a dose of 0.4 mumol. The H2 receptor antagonists metiamide and oxmetidine (1.6 mumol) stimulated basal prolactin secretion and did not prevent the response to histamine. A dose of 0.4 or 1.6 mumol imidazole (the ring structure contained in cimetidine, SKF-92408, metiamide, and oxmetidine) had no effect on basal or histamine-stimulated prolactin secretion. The findings indicate that cimetidine stimulates prolactin secretion by a non-specific action when infused centrally at high doses. In contrast, when infused at lower doses cimetidine inhibits the basal and histamine stimulated secretion by blockade of H2-receptors. The prolactin-stimulatory action of cimetidine was not due to an H2-agonist effect, since ranitidine did not prevent the response. Cimetidine did not stimulate prolactin secretion via an effect on the dopaminergic system, since the drug had no effect on the dopamine concentration in hypophysial portal blood or in hypothalamic tissue and since inhibition of the dopamine synthesis by alpha-methyl-p-tyrosine did not prevent the cimetidine-induced prolactin release. PMID- 2888252 TI - Comparison of atracurium and vecuronium in anaesthesia for renal transplantation. AB - In a controlled study, equipotent doses of atracurium (20 patients) or vecuronium (22 patients) were given randomly to patients with chronic renal failure anaesthetized for renal transplantation. There were no statistically significant differences in the degree of muscle relaxation (electromyographic twitch response) and circulatory parameters. Plasma histamine concentration increased in three patients after the first dose of atracurium, but in none of the patients could any signs of allergic reactions be observed. Tracheal intubation was difficult in six patients of the atracurium group, all of whom had diabetes mellitus and varying degrees of neck stiffness. The neuromuscular block response in diabetic uraemic patients was similar to that in other uraemic patients. PMID- 2888251 TI - TSH binding proteins in rat and human serum. AB - When serum of hypothyroid rats was fractionated on a Sephadex G-100 column, most of the immunoreactive TSH was found as a front running peak, together with the high molecular weight serum proteins. Similarly, a rTSH preparation (10 mU), chromatographed in the presence of 1 ml of normal rat serum also migrated at the front, however, when a high load of TSH (4.4 U) was added to 1 ml of serum, two immunoreactive peaks were found, suggesting the saturation of the front running fraction. Immunoelectrophoresis and autoradiography of rat or human sera containing the respective 125I-labelled TSHs showed binding of the labelled TSH to IgG, alpha-2-macroglobulin, and to a third unidentified protein, migrating near the albumin line. In order to determine if the bound TSH is biologically active, the high molecular weight protein fraction was separated from hypothyroid rat serum by 45% ammonium sulphate precipitation. Immunoreactivity was determined by RIA and the biological activity was determined, in vitro, by the stimulation of 99Tc uptake by FRTL-5 cells. The 45% ammonium sulphate precipitate contained almost all of the immunoreactivity and the bioactivity of the TSH of whole serum. These results indicate that: a) The endogenous circulating TSH in the hypothyroid rat exists mainly in a protein-bound form and this protein-bound TSH contains most of the hormonal bioactivity of the serum. b) Exogenous TSH binds to serum proteins in euthyroid and hypothyroid rats and in humans. There are three protein fractions in these sera that bind TSH, one of which is an immunoglobulin. The occurrence of TSH binding immunoglobulins may involve autoimmune mechanisms. PMID- 2888253 TI - Premedication with midazolam in out-patient general anaesthesia. A comparison with morphine-scopolamine and placebo. AB - Strong premedication may prolong recovery and cause side-effects after short surgical procedures in general anaesthesia. To be operated without premedication may be unpleasant for the patient. Midazolam is a water-soluble benzodiazepine with rapid onset and short half-life. In a randomized study with 193 female patients, we compared the effects and side-effects of three different premedicants i.m.: midazolam, morphine-scopolamine (Mo-Scop) and placebo. Midazolam and Mo-Scop had an equal and significantly better effect than placebo on preoperative anxiety and alertness. Side-effects like nausea, dry mouth and prolonged recovery occurred significantly more often in the Mo-Scop than the midazolam or placebo groups. The midazolam-premedicated patients had significantly more amnesia compared with the other two groups. Only 3% of the patients would prefer no medication before anaesthesia, whereas 80% would prefer a combination of an anxiolytic and hypnotic premedication. Sixty-three percent of the patients would prefer a premedicant administered by injection. The results indicate that midazolam i.m. is an effective premedicant, with few side-effects, for short procedures in general anaesthesia. PMID- 2888254 TI - Histology of the normal and retained equine testis. AB - Abdominal, inguinal and scrotal testes of horses were examined grossly and by light microscopy. An average of 1.5, 2.3 and 4.6 layers of spermatogenic cells, and mean seminiferous tubule diameters of approximately 66.2, 83.6 and 146.6 micron in the abdominal, inguinal and scrotal testes, respectively, were recorded. The interstitial spaces and the number of interstitial cells (of Leydig) seemed to be increased while spermatogenesis appeared to be arrested in the retained testes. Early spermatocytes were the most mature stages of the spermatogenic cells in the retained testes. An extensive vacuolation of spermatogenic cells was evident in these testes. The changes may result due to a high temperature of the abdominal environment in concert with the altered production of androgens. PMID- 2888255 TI - Somatostatin-containing and other endocrine cells in the pancreas of the spectacled caiman. AB - Light-microscopic immunocytochemistry was used to localize 4 major pancreatic hormones in the pancreas of the spectacled caiman, Caiman fuscus. Somatostatin, insulin, glucagon and pancreatic polypeptide were localized by the peroxidase antiperoxidase complex technique. A relatively large population of somatostatin containing D cells was present. The D cells were nearly as numerous as the insulin-containing B cells and glucagon-containing A cells which were the most common cell types. All three cell types were commonly intermingled with one another in endocrine cell areas. Pancreatic polypeptide-reactive F cells were absent from some regions of the pancreas, but where present were related to other endocrine cell types. Functional properties of the pancreatic endocrine cells in this anatomical variant remain to be determined. PMID- 2888256 TI - Age of the cell culture: a factor influencing hormonal imprinting of Tetrahymena. AB - Insulin imprinting of Tetrahymena pyriformis in different growth phases had been investigated. Cells formed in the early logarithmic phase (18-hour culture) showed enhanced hormone binding at the second encounter with the hormone proving that imprinting had developed. This phenomenon was not observed in cells formed in the late logarithmic phase (42-hour culture) or in the stationary phase (66 hour culture). Lipid transformation processes, alteration of the guanyl cyclase activity and enhanced cell division may be responsible for this effect. Cell growth phase G1 was especially favourable for development of imprinting. PMID- 2888257 TI - Somatostatin suppression of meningioma cell proliferation in vitro. AB - Considering the presence of a stereospecific receptor for somatostatin (SST) in human meningioma cells and the possible involvement of this neuropeptide in the growth control of certain meningioma cell lines, the effects of SST on the proliferation of human meningioma cells in vitro was investigated. Tumour tissues for primary cell cultures were obtained surgically from 2 women with histopathological diagnosis of meningothelial meningioma. The incorporation of [3H]-thymidine into meningioma cells DNA was measured as an index of the cells proliferation. It was shown that SST (10(-7)-10(-5) M) significantly inhibited the [3H]-thymidine incorporation. The results have indicated that SST may have an antiproliferative effects on the meningioma tumour cells in vitro. PMID- 2888258 TI - The effect of non-nutritive sucking on plasma insulin, gastrin, and somatostatin levels in infants. AB - The aim of the present investigation was to study the effect of non-nutritive sucking on plasma levels of insulin, gastrin, and somatostatin in infants. These hormones were measured with radioimmunoassay in plasma collected from fullterm and preterm infants sucking a pacifier. In fullterm infants, sucking caused a significant increase of insulin levels from 13 +/- 10 microU/ml to 40 +/- 36 microU/ml and 21 +/- 17 microU/ml after 45 sec and 5 min respectively, from when the infants started sucking. A similar pattern was seen in preterm infants. In contrast, gastrin and somatostatin levels were not significantly affected. We suggest that sucking causes an activation of the vagal nerve, which results in the release of insulin. We also suggest that in infants, oral feeding is superior to bolus feeding, since in the latter case no vagal activation and consequently no release of hormones with anabolic properties occurs. PMID- 2888259 TI - Gastroesophageal reflux and asthma medication. PMID- 2888260 TI - Immunohistochemical demonstration of peptide YY in gastrointestinal endocrine tumors. AB - Fourteen cases of gastrointestinal endocrine tumors were examined immunohistochemically for peptide YY, pancreatic polypeptide, glucagon, and somatostatin. Peptide YY cells were present in seven tumors, pancreatic polypeptide cells in eight tumors, glucagon cells in six tumors, and somatostatin cells in nine tumors. All 7 rectal endocrine tumors examined were found to contain peptide YY, while in the tumors of the other sites peptide YY cells were not detected. Peptide YY cell population in the rectal tumors was small to moderate in comparison with pancreatic polypeptide and glucagon cell population. This study suggests that peptide YY cells may be a common constituent of rectal endocrine tumors together with pancreatic polypeptide and glucagon cells, and that the peptide YY spectrum of gastrointestinal endocrine tumors may be closely related to the location of the tumors. Moreover, it can also be said that peptide YY may be used as one of the markers of rectal endocrine tumors. PMID- 2888261 TI - Mechanisms underlying the small intestinal fluid secretion caused by arachidonic acid, prostaglandin E1 and prostaglandin E2 in the rat in vivo. AB - Prostanoids were given intraluminally (PGE2) or infused close intra-arterially (PGE1 and PGE2) or arachidonic acid was administered intraluminally to denervated jejunal segments of the rat in vivo. These experimental manoeuvres caused a net fluid secretion, although a 1,000-fold higher concentration of the prostanoids was needed from the luminal than from the vascular side. I.v. hexamethonium or serosally applied lidocaine diminished the induced fluid secretion suggesting that the prostanoids act mainly by eliciting local secretory reflexes in the enteric nervous system. This nerve-mediated secretion is not accompanied by any increase in tissue cAMP. However, at higher i.a. concentrations of PGE2 there seems to be a non-neurogenic effect on the enterocytes associated with an increase in tissue cAMP. PMID- 2888262 TI - Long-term use of benzodiazepines in psychiatric inpatients. AB - During the past few years the problem of over-prescribing benzodiazepines has been increasingly discussed. However, up to now exact data on the extent of an abuse of these substances are relatively scarce and controversial. An analysis done at the Psychiatric State Hospital Weinsburg from 1974 to 1983 regarding the frequency of the diagnosis "Benzodiazepine-dependence" showed that in only 150 cases (0.5%) out of almost 33,000 admitted patients was the diagnosis benzodiazepine-abuse justified, with an increase since the year 1980. During a prospective study of the quarterly incidence in 1984, 18.5% of the patients admitted met the criterion of long-term use of benzodiazepines (continuous use for more than 3 months). Sociodemographic and clinical data are presented and an index of abuse/dependence is proposed. PMID- 2888263 TI - [Acute renal insufficiency caused by glaphenine. Presentation of a case and review of the literature]. PMID- 2888264 TI - European courses of neurosurgery and other training and postgraduate education activities of the European Association of Neurosurgical Societies. PMID- 2888265 TI - Drug abuse: control through national and international regulatory practice. PMID- 2888266 TI - Cytochemical studies of the neural circuitry underlying pain and pain control. PMID- 2888267 TI - Spinal infusion of opiates and somatostatin. PMID- 2888268 TI - Biochemistry of the nervous system. PMID- 2888269 TI - The interleukin-2 receptor on normal and malignant lymphocytes. AB - Interleukin-2 (IL-2) is a lymphokine synthesized by T cells following activation. Resting T cells do not express IL-2 receptors, but receptors are rapidly expressed on T cells following interaction of the antigen-specific T-cell receptor complex with appropriately processed and presented antigens. Anti-Tac, a monoclonal antibody that recognized the IL-2 receptor, has been used to purify the receptor. The recognized the IL-2 receptor, has been used to purify the receptor. The receptor is a 55-Kd glycoprotein comprised of 272 amino acids including a single 19-amino transmembrane domain and a short intracytoplasmic domain composed of 13 amino acids at the carboxy terminus. Normal resting T cells and most leukemic T-cell populations examined did not express IL-2 receptors; however, the leukemic cells of all patients with human T-cell lymphotrophic virus (HTLV-I)-associated adult T-cell leukemia (ATL) expressed the Tac antigen. In HTLV-I-infected cells, the 42-Kd long open reading frame (tat) protein encoded in part by the tat region of HTLV-I may act as a transacting activator that induces transcription of the IL-2 receptor gene, thus providing an explanation for the constant association of HTLV-I infection of lymphoid cells and IL-2 receptor expression. The constant display of large numbers of IL-2 receptors which may be aberrant in the ATL cells may play a role in the uncontrolled growth of these leukemic T cells. Patients with the Tac-positive ATL are being treated with both unmodified and toxin-conjugated forms of anti-Tac monoclonal antibody directed toward this growth factor receptor. PMID- 2888270 TI - IL-2 receptor gene activation by ATL-derived factor (ADF). PMID- 2888272 TI - [Bore wire osteosynthesis in distal radius fracture]. AB - Treatment results and complications of 404 percutaneous drill wire fixations in patients with dislocated radial fracture of typical situation will be reported. The most frequent complications were secondary impression of fracture, transient paraesthesia as well as perforation through the skin by drill wire. There was no case of osteitis or pseudo-arthrosis. Treatment results were judged excellent or good in 84% of cases, satisfactory in 11% and poor in 5%. For dislocated wrist fractures and for elderly patients osteosynthesis with percutaneous drill wire according to Willenegger is superior to non-operative procedures. PMID- 2888271 TI - [Total or subtotal amputation of a long finger with destruction of the metacarpophalangeal joint--regaining function by replantation?]. AB - Destruction of the metacarpophalangeal joint represents one of the most unfavourable situations making it extremely difficult to attain useful finger function after replantation. Single fingers damaged in this way may therefore not be replanted. If several long fingers are affected, a slight residual mobility in the metacarpophalangeal joint can be attained by joint reconstruction or prosthesis implantation. If the thumb is destroyed at the same time or is not supplied along with the severed hand, heterotopic replantation of a long finger of which the metacarpophalangeal joint has been destroyed is a way of attaining an adequate thumb length. PMID- 2888273 TI - [Bore wire osteosynthesis in distal radius fractures]. AB - In the presence of an area of extensive dorsal comminution percutaneous pinning is indicated in a typical distal radius fracture (Colles). It enlarges the stability and thus helps avoiding a secondary dislocation of the fracture. Indication and technique of this procedure are discussed following a series of 66 patients. Typical mistakes are as follows: insufficient reduction, poor diverging of the K-wires and improper anchoring in the opposite cortex. Avoiding of these possible faults leads to good final results. Flexion fractures and extensive shattering of the bone are contraindications for percutaneous pinning of these fractures. PMID- 2888274 TI - [Choice of surgical procedure of the distal radius. Bore wire versus plate]. AB - At the distal radius surgical treatment is indicated in fractures with defect, compression zone or re-dislocation, fractures with joint depression, open fractures and fractures with neurological and circulatory impairment. K-wire transfixation is mainly indicated in unstable fractures of elderly patients, in juvenile fractures with involvement of the epiphyseal line, and in simple intraarticular fractures, if the articular surface can be restored easily. T plate osteosynthesis is the method of choice in fractures with volar displacement (Smith-Goyrand), in dislocated unstable intraarticular fractures with at least two main fragments to support screws securely, in unstable extraarticular fractures, especially with large zones of compression or defects, in combined fractures of the scaphoid and the styloid processus of the radius, and in corrective osteotomies after posttraumatic misalignment. Basing on an evaluation of our own experience with 226 K-wire transfixations and 159 T-plate osteosyntheses, indication, surgical technique, postoperative treatment and results of the two methods are compared. PMID- 2888275 TI - [Tension band osteosynthesis--a method fraught with complications in surgical fracture treatment?]. AB - Tension-band osteosynthesis is a simple and well-known procedure in the surgical treatment of fractures. An analysis of 180 patients, operated on in our hospital or admitted for corrective osteosynthesis, showed 23 mistakes of a minor degree and 20 major mistakes. Malpositioning of K-wires or cerclages caused the minor mistakes. Loosening of metal, failure of osteosynthesis or poor adaptation of fragments were responsible for the major mistakes. Tension-band osteosynthesis can only be successful if the principles of biomechanics are realised, if tension forces are transmitted by the implant, if bony buttressing is achieved by the fragments, and if torsion forces are converted into compressive forces (Pauwels). PMID- 2888276 TI - [Temporary bore wire osteosynthesis in fractures of the head of the humerus]. AB - In a series of 27 patients it is shown that percutaneous K-wiring in fractures of the head of the humerus can be regarded complementary to the conservative treatment. It can as well compete with open reduction and internal fixation by means of plate-or screw-osteosynthesis. The advantages of this method are as follows: simple procedure, quick operation, sufficient stability and easy removal of the implants particularly in elderly patients. PMID- 2888277 TI - [Bore wire osteosynthesis in injuries of the foot]. AB - Severe foot lesions with fractures and/or dislocations require the best reconstruction of form and function. The essential prerequisite for an undisturbed healing consists of an exact reduction with reconstruction of skeletal foot structure by osteosynthesis according to the lesions of the soft tissue. In case of extended lesions of the soft tissue, the closed reduction with reconstruction of the vault of the foot and the retention with Kirschner-wires, if necessary combined with a fixateur externe, has proven to be successful for stabilization. PMID- 2888278 TI - [Subtalar arthrodesis with tension screws from the plantar side]. PMID- 2888279 TI - [Bore wire osteosynthesis]. AB - Osteosynthesis by Kirschner-wires still maintains its importance in the treatment of certain fractures. This kind of stabilization is either used temporarily within the scope of an internal fixation as well as in adaptation osteosynthesis or in applying a tension band wiring. Especially in fractures of the growing skeleton and in fractures of elderly patients K-wire fixation often represents the method of choice. The various indications for stabilization by means of Kirschner-wires is demonstrated in some typical fracture localizations. PMID- 2888280 TI - The antiinflammatory moiety of sulfasalazine, 5-aminosalicylic acid, is a radical scavenger. AB - Using a novel spectrophotometric assay to detect free radical scavengers, the effects of sulfasalazine, a compound frequently administered in the treatment of chronic inflammatory bowel disease, and its main metabolites, 5-aminosalicylic acid (5-ASA), sulfapyridine, and N-acetyl-5-ASA, were compared with biological antioxidants (nordihydroguaiaretic acid (NDGA), alpha-tocopherol, and ascorbic acid) and antiinflammatory salicylates (acetylsalicylic acid and sodium salicylate). The results show that 5-ASA, but neither sulfasalazine and its other metabolites, nor the salicylates, shares with the biological antioxidants the property of being a potent scavenger of free radicals. Since 5-ASA is formed in millimolar concentrations in the colon of sulfasalazine-treated patients this mode of action may explain the beneficial effect of sulfasalazine in inflammatory bowel disease. Locally formed 5-ASA may break the free radical chain reaction initiated and maintained by activated phagocytes, thus arresting the perpetuating tissue destruction. This mechanism may indicate a general potential for radical scavengers in chronic inflammation. PMID- 2888281 TI - Relation between pharmacological response and receptor binding with histamine blocking drugs. Irreversible antagonism of three analogues of mifentidine on right atrium and cerebral cortex of the guinea-pig. AB - The effects of the H2-receptor antagonists cimetidine, ranitidine, mifentidine and three analogues of mifentidine, were studied on the spontaneously beating right atrium (H2-antagonism) and membranes of the cerebral cortex (displacement of 3H-tiotidine), both obtained from the male guinea-pig. The choice of these compounds was based on preliminary experiments in which some mifentidine analogues were shown to displace tiotidine from the H2-receptor in a deviant manner. In the present study we investigated the relation between pharmacological response and receptor binding, also testing the degree of irreversible antagonism of these compounds in the atrium (functional) and cerebral cortex (binding) model. Our data indicate that a relation between the two different approaches for measuring the effect on the H2-receptor can be found, although some differences emerged as well. PMID- 2888282 TI - Pulmonary aerosol actions of LY188695 (KB2413), a new potent H1-receptor antagonist. AB - The new potent H1 receptor antagonist, LY188695 (KB2413), was delivered to guinea pigs as a pulmonary aerosol and its ability to inhibit histamine-induced airway obstruction examined. Aerosol LY188695 was more effective than inhaled chlorpheniramine or clemastine in reducing the pulmonary gas trapping produced by histamine challenge. Lung antihistamine effects occurred within minutes of a brief, low concentration aerosol exposure and persisted for at least 1 hour. LY188695 aerosol treatment did not produce significant inhibition of methacholine induced gas trapping. Although systemic antihistamine effects occurred 50 minutes after LY188695 inhalation, aerosol administration produced an enhanced local (i.e., lung) action compared to intravenous delivery. PMID- 2888283 TI - Biologic properties and genome structure of the recombinants between ectromelia and rabbitpox viruses. AB - Administration of rabbitpox virus (RPV) DNA, cleaved into 2 fragments by SmaI restrictase, into ectromelia virus (EMV)-infected chick fibroblast cells yielded recombinants whose properties were characteristic of both parents. Some recombinants capable of producing RPV-type lesions upon intracutaneous (i.c.) infection of rabbits could also produce EMV-specific lesions upon footpad inoculation of mice. The analysis of some recombinants as well as vaccinia virus strains has shown that the ability of the virus to reproduce when injected into the mouse footpad is a necessary, but not a sufficient condition for production of EMV-type lesions. According to restrictase analysis of recombinant DNA, the genome of recombinants mainly consists of RPV DNA sequences with insertions of small EMV DNA fragments. PMID- 2888285 TI - Preparation and evaluation of anti-species and antiviral peroxidase conjugates. AB - Several antispecies peroxidase conjugates from human and rabbit immunoglobulins G (IgG) and a conjugate from IgG fraction of hyperimmune rabbit serum against the membranes of herpes simplex virus type 1 (HSV-1) infected cells have been prepared and characterized. The conjugates when tested in enzyme immunoassay for detection of antiherpetic antibodies in human and hyperimmune rabbit sera, as well as for detection of HSV-1 antigen in infected Vero cells appeared active and highly specific. Comparison with the peroxidase conjugates from antiherpetic IgGs prepared by means of ion- exchange and affinity chromatography has shown similar activities. PMID- 2888284 TI - Influenza virus depresses the PFC response of mice by affecting T-cell function. AB - Five influenza virus strains of type A and one strain of type B were used to elicit suppressive effect on the formation of antibody producing cells in response to sheep red blood cells (SRBC) both in vivo and in vitro. Not only live virus but also the formalin inactivated one exerted immunosuppression (IS). Although intranasal infection only could cause disease in mice, it exerted no IS which, in contrast, occurred after intraperitoneal or intravenous injection of the virus. In nude mice these effects were not seen, but they could be elicited when transferred with normal T cells. The antibody response to T cell independent antigen such as DNP was normal. Thus, it was proved that influenza virus induced T cell dependent immunodeficiency. However, T cell enriched population from infected mice when cultured with normal spleen cells could not suppress their PFC response in vitro. This suggested that suppressor T cells were not required for the immunodeficiency caused by influenza virus. PMID- 2888286 TI - Enzyme immunoassay for detection of antibodies against herpes simplex virus with the use of different viral antigens. AB - Enzyme-linked immunosorbent assays (ELISA) for detection of antibodies to herpes simplex virus type 1 (HSV-1) have been performed by using different immunosorbents prepared by passive adsorption of four HSV-1 antigen preparations to the wells of polystyrene microtitre plates in order to compare the the sensitivity, specificity and reproducibility of the tests. The following antigen preparations have been used: virus-infected native Vero cells and their lysates, membrane glycoproteins and virus nucleocapsid proteins. The optimal conditions have been established for each assay system: the concentrations of adsorbed antigen and the "threshold" values of the optical density. For each antigen tested except of the nucleocapsid (NC) proteins, comparable antibody titres were found in the sera of 6 patients with different forms of herpes infections and in 86 healthy subjects. In the sera of 6 herpetic patients the antibody titres were higher against NC antigen than against other antigen preparations. PMID- 2888287 TI - Dynamics of serum markers in the different course of hepatitis B virus (HBV) infection. AB - The presence of serum markers of hepatitis B virus (HBV) infection in different stage of illness has a specific pathogenic and diagnostic significance. Based on the frequency of the appearance of HBV markers in patients' sera at different stages of the illness, we attempted a grouping possibly helpful for differentiation, epidemiologic and prognostic evaluation of hepatitis. The significance for chronic disease development of the dynamics of HBV marker levels in the serum is discussed. PMID- 2888288 TI - Biological properties of Estero Real virus. AB - The pathogenicity for animals, multiplication characteristics in animals, chick embryos and cells, and antibody formation to the Estero Real (ER) virus are reported. PMID- 2888290 TI - Coxiella burnetii antigens for detection of Q fever antibodies by ELISA in human sera. AB - Different concentrations of chemically-treated (by potassium periodate oxidation or mild acid hydrolysis) purified phase I Coxiella burnetii (C.b.) corpuscles and natural (untreated) purified phase I and phase II C.b. corpuscles were compared by ELISA for detection of both phase I (directed to antigen 1) and phase II (directed to antigen 2) antibodies in human Q fever convalescent sera. As to the absorbance values the most sensitive was the antigen obtained by mild acid hydrolysis (0.1 mol/l HCl of phase I corpuscles for 30 min at 100 degrees C) followed by phase I corpuscular antigen (treated with 0.01 mol/l potassium periodate for 4 hr at 45 degrees C). The natural phase I (the 3rd egg passage) and phase II (the 162th egg passage) C.b. corpuscles gave lower absorbance with some sera not even distinguishing the 6th egg passage (EP6 or EP3 in phase I) from EP 162 or from negative controls. PMID- 2888289 TI - Peroxidase labelled mumps virus antigens and their application in IgM capture immunoassay: first experience. AB - Three types of mumps virus antigen have been prepared: virion antigen (MV); soluble nucleoprotein (NP) antigen; envelope glycoprotein (eGp) antigen. These antigens were coupled directly with horse-raddish peroxidase and tested by IgM capture technique against selected human sera. The advantage of the suggested design, in addition to general superiority of the IgM-capture systems, lies in its selectivity achieved by introducing a monoclonal antibody for IgM binding and in time saving due to the use of labelled antigen without the loss of sensitivity and specificity. The assay fulfils the criteria for quick viral diagnostic. Our first experience on application of the labelled antigens in enzyme immunoassay (EIA) is described. PMID- 2888291 TI - Abrogation of Junin virus encephalitis by critical cyclophosphamide timing and dosage. AB - Junin virus-induced encephalitis in suckling mouse is a delayed-type hypersensitivity reaction, whose immunopathologic nature has been proven by suppressing the thymus-dependent response. Cyclophosphamide (CY) given at day +6 post-infection (p.i.) has been shown to modulate infection, presumably by TDTH lymphocyte inactivation. To determine critical timing and i.p. drug dose, brain histology and survival were studied in 3-day-old Balb/c mice, inoculated i.c. with Junin virus. Optimal protection was achieved with a non-toxic, 50 mg/kg CY dose at day 6 p.i. (+6): no brain tissue damage was detected in animals killed at day +12, when the necropsied controls exhibited widespread lesions. Other timings (day +3, +4, +5) proved less effective. As regards alternative dosage at day +6, 30 mg was useless, and severe leptomeningitis was evident, whereas 40 mg significantly lowered mortality, and lesions were much milder and less constant. It seems that the 50 mg/kg CY dose must be administered at a critical time p.i. to inactivate sensitized TDTH lymphocytes and to reduce mortality and CNS pathology significantly. PMID- 2888292 TI - Physico-chemical properties of Estero Real virus. AB - Estero Real (ER) virus can pass through the Millipore membrane filter of 0.22 micron pore size; it is sensitive to heating, sodium deoxycholate (SDC) and ether treatments. It replicates to the highest titres in a slightly alkaline medium. Actinomycin D (Act. D) does not prevent its multiplication in cell culture. The presence of heamagglutinin was ascertained. PMID- 2888293 TI - In vivo opsonization of Japanese encephalitis virus by peritoneal macrophages in infant mice. AB - Anti-JE antibody in nonneutralizable concentration and Concanavalin A are synergistic in protecting 10-day-old mice from lethal JE virus challenge by i.p. route. PMID- 2888294 TI - Biochemistry of rickettsiae: recent advances. AB - The application of new biotechnology to the study of the biochemistry of rickettsiae was a prominent feature of the presentations at the 3rd International Symposium on Rickettsiae and Rickettsial Diseases, held in Smolenice near Bratislava in September 1984. This review is an attempt to summarize recent advances leading up to these presentations as well as the studies that have been reported in the two years since the meeting. Since rickettsiae are intracellular parasites, most reviews deal with the interaction of rickettsiae with host cells. It is useful, however, to focus also--as we have done--on the properties of rickettsiae that can be demonstrated in the absence of their hosts, although, undoubtedly, many of these properties reflect adaptation to an intracellular microenvironment. PMID- 2888295 TI - Coxsackievirus group B type 4 induced myocardial infarctions? PMID- 2888296 TI - A symposium: Use of beta blockers as antiarrhythmic agents. December 12-12, 1986, San Juan, Puerto Rico. Proceedings. PMID- 2888297 TI - Antiarrhythmic effects of beta-adrenergic blocking agents in benign or potentially lethal ventricular arrhythmias. AB - Classification of ventricular arrhythmias into those that are benign, potentially lethal and lethal is based on their associated risk for producing sudden cardiac death. This classification system is useful in defining indications for the treatment of ventricular arrhythmias and predicting differential rates of antiarrhythmic drug efficacy and toxicity. Whether the reduction of potentially lethal ventricular arrhythmias will prevent sudden cardiac death remains to be determined. The class II antiarrhythmic agents--the beta-adrenergic blocking drugs--have been shown to reduce sudden cardiac death in postmyocardial infarction patients, but the precise mechanism of their effect has not been defined. beta blockers are efficacious in approximately 50% of patients with benign or potentially lethal ventricular arrhythmias. This response is comparable to that seen with the class IA agent disopyramide or the class IB agents tocainide and mexiletine. beta blockers have favorable side-effect profiles including a low incidence of proarrhythmia and a lack of organ toxicity such as hepatitis, pulmonary fibrosis or agranulocytosis, which are concerns with class I and class III antiarrhythmic drugs. The proper dosage of the beta blocker is critical in limiting adverse effects. In a study of 23 patients with benign or potentially lethal ventricular arrhythmias, 11 (48%) of the patients responded to nadolol with a reduction of greater than 75% in arrhythmia frequency, and several patients responded at nadolol dosages as low as 10 mg daily. Thus, it is plausible to consider beta blockers as first-choice antiarrhythmic therapy, even in patients with left ventricular dysfunction when sympathetic tone is not required to maintain cardiac compensation. PMID- 2888298 TI - Electrophysiologic effects of beta blockers in ventricular arrhythmias. AB - Beta-adrenergic receptor blocking agents are effective antiarrhythmic drugs in patients with ventricular arrhythmias. However, these agents exert little or no measurable electrophysiologic effect on normal Purkinje and ventricular muscle fibers when administered acutely. They prevent catecholamine-induced increases in Purkinje fiber automaticity and may interfere with catecholamine-dependent slow responses. beta-adrenergic blocking drugs also prevent the decrease in ventricular fibrillation threshold induced by catecholamines. In the acutely ischemic ventricle, some beta blockers selectively depress conduction within the ischemic zone. The long-term administration of some beta blockers has, in contrast to their short-term effects, been shown to prolong action potential duration and effective refractory period in the ventricle. Which of these observed electrophysiologic effects, either alone or in combination, contributes to the ventricular antiarrhythmic effects of beta-blocking drugs in man is at present unknown. PMID- 2888299 TI - Electrophysiology of beta blockers in supraventricular arrhythmias. AB - beta-adrenergic blocking agents are efficacious in the treatment of patients with a variety of supraventricular tachycardias, based directly on their capacity to counter the effects of beta-adrenergic stimulation on sinus and atrioventricular nodal tissue. Specifically, beta blockers depress sinus node automaticity and inhibit atrioventricular nodal function by prolonging refractoriness and slowing conduction. Supraventricular arrhythmias that depend on these structures either for perpetuation or for conduction to the ventricles are predictably sensitive to beta blockade. These arrhythmias include sinus tachycardia, sinoatrial reentrant, atrioventricular nodal reentrant (dual pathway) and atrioventricular reciprocating (concealed bypass tract) tachycardias, as well as atrial flutter and fibrillation. beta blockers may also be used, in selected patients, to inhibit catecholamine-facilitated accessory pathway function by prolonging refractoriness. beta blockers offer particular clinical advantages, including an acceptable side-effect profile, titratable effect, varied pharmacology and reasonable concordance between efficacy of parenteral and oral dosage forms. The key element in the most effective use of these drugs appears to be an accurate arrhythmia diagnosis that allows for the most appropriate application of a reliable treatment form. PMID- 2888300 TI - Beta-blocker therapy for the Wolff-Parkinson-White syndrome. AB - Two types of arrhythmias are associated with the Wolff-Parkinson-White syndrome: those in which the accessory pathway is a required part of the reentrant circuit, e.g., orthodromic atrioventricular reciprocating tachycardia, and those that conduct over the accessory pathway but do not require its activation for maintenance of tachycardia, e.g., atrial flutter/fibrillation. Increased sympathetic tone shortens the refractoriness of atrial and ventricular tissue; however, conduction in the atrium and ventricle is not considered the limiting factor for maintenance of atrioventricular reciprocating tachycardia or conduction over the accessory pathway in atrial arrhythmias. Intravenous beta adrenergic blockers given to patients in the resting state have a minimal to moderate effect in depressing atrioventricular nodal conduction, but have little or no effect on accessory pathway refractoriness or conduction in most patients. In patients presenting with atrioventricular reentry, intravenous administration of beta-adrenergic blocking drugs often is not effective to terminate tachycardia. However, long-term oral therapy with these agents may be beneficial, especially in patients in whom enhanced sympathetic tone is responsible for the initiation or maintenance of tachycardia. PMID- 2888301 TI - Long-term efficacy and safety of beta-adrenergic receptor antagonists for supraventricular tachycardia. AB - The efficacy and safety of nadolol and atenolol, 2 new long-acting beta adrenergic receptor antagonists, were evaluated in patients with recurrent supraventricular tachycardia (SVT). Intravenous and oral drug therapy was administered to patients with atrioventricular reentrant tachycardia and atrioventricular nodal reentrant tachycardia. Efficacy was judged on a short-term basis by programmed electrical stimulation and on a long-term basis by clinical parameters and serial ambulatory electrocardiographic recordings during long-term follow-up. In addition, the usefulness of programmed electrical stimulation to predict long-term efficacy was evaluated. Intravenous nadolol prevented induction of SVT in 6 of 8 (75%) patients with atrioventricular nodal reentrant tachycardia, and oral nadolol prevented induction of SVT in 5 of 6 (83%) responders to intravenous nadolol. No episodes of sustained SVT recurred in these 5 patients during follow-up. Intravenous nadolol also prevented induction of SVT in 2 of 17 (11%) patients with atrioventricular reentrant tachycardia. Both patients remained non-inducible during treatment with oral nadolol, and neither experienced recurrence of SVT during follow-up. Intravenous atenolol prevented induction of SVT in 5 of 6 (83%) patients with atrioventricular nodal reentrant tachycardia. Oral atenolol prevented induction of atrioventricular nodal reentrant tachycardia in 4 of 5 (80%) patients responding to intravenous atenolol, and none of these 4 patients experienced a clinical recurrence. Intravenous atenolol prevented induction of SVT in 1 of 4 (25%) patients with atrioventricular reentrant tachycardia. Oral atenolol prevented induction of SVT in this patient and the arrhythmia has not recurred during follow-up. During follow-up (1 to 37 months), drug tolerance and compliance have been excellent with a low incidence of adverse reactions (11%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888302 TI - Comparison of carvedilol and atenolol for angina pectoris. AB - The antianginal efficacy of carvedilol, a novel beta-blocking agent with vasodilating action, and atenolol were compared in 12 patients with stable effort angina and a positive stress test response. All patients received single doses of placebo, carvedilol, 25 and 50 mg, and atenolol, 50 mg. Heart rate at rest was reduced by 11 and 12 beats/min with both drugs, but only carvedilol, 50 mg, reduced blood pressure at rest. Both carvedilol, 50 mg, and atenolol, 50 mg, increased mean exercise time (24% and 34%, respectively, compared with placebo), time to angina (35% and 51%, respectively), and time to 1 mm of ST-segment depression (54% and 102%, respectively, p less than 0.05 carvedilol vs atenolol). Carvedilol, 25 mg, produced smaller, directionally similar changes in exercise performance, which did not reach statistical significance except for time to 1 mm of ST depression. Both drugs in the 50-mg dose reduced ST-segment depression similarly at maximal and submaximal work levels and lowered heart rate and rate pressure product at maximal and submaximal work. Carvedilol, 50 mg alone, significantly lowered maximal systolic pressure and rate-pressure product at 1 mm of ST-segment depression. Despite some evidence of vasodilator activity for carvedilol, there was no significant difference in antianginal efficacy with a conventional beta-blocking drug. PMID- 2888303 TI - Paracervical ganglia of the female rat: histochemistry and immunohistochemistry of neurons, SIF cells, and nerve terminals. AB - The paracervical ganglia of the female rat were studied to elucidate the variety of neural elements in the ganglia. Light and electron microscopy, histochemistry, and immunohistochemistry were employed to reveal subtypes of neurons; small, intensely fluorescent (SIF) cells; and nerve terminals and to examine the relationships between these elements. On the basis of their histochemical markers, four subtypes of principal neurons were identified: acetylcholinesterase (ACHE)-positive, noradrenergic, neuropeptide tyrosine-immunoreactive (NPY-I), and vasoactive intestinal polypeptide-immunoreactive (VIP-I). The NPY-I neurons appeared to be the most numerous and the noradrenergic the least common type of neuron. Four subtypes of chemically coded SIF cells were revealed: catecholamine containing, NPY-I, and those immunoreactive for calcitonin-gene-related peptide (CGRP-I) and cholecystokinin-octapeptide (CCK-8-I). The SIF cells were present as single cells among and adjacent to principal neurons and as large clusters near the edges of the ganglia or in nearby nerve trunks. Synaptic contacts on SIF cells, or between SIF-cell processes and neurons, were not observed. Seven subtypes of nerve terminals were stained: ACHE-positive, CGRP-I, CCK-8-I, VIP-I, substance P-I, enkephalin-I, and atrial natriuretic factor-I. Nerve terminals enwrapped the neurons as perineuronal plexuses in synaptic-like relationships. These results demonstrate that the paracervical ganglia of the female rat are a complex system of neural elements. For example, several classes of chemically coded neurons, SIF cells, and terminals exist in the ganglia. Each of these components contains a number of substances, some of which are putative neurotransmitters, which could influence activity in the ganglia or in the effector organs innervated by the ganglia. PMID- 2888304 TI - Optimal welding of beta titanium orthodontic wires. AB - Today the orthodontist is confronted by an array of new orthodontic wire materials that, when applied to appliance design, can vastly increase the flexibility and versatility of therapy. Welded joints, especially for the newer titanium alloy wires, provide a means to extend the useful applications of these materials. The purpose of this study was to determine the optimum settings for electrical resistance welding of various configurations of titanium-molybdenum (TMA) wires. Specimens were of a t-joint configuration and were mechanically tested in torsion to simulate the failure mode most often observed in clinical practice. Variables included wire size, wire orientation, and welding voltage. Results indicated that excellent welds can be obtained with very little loss of strength and ductility in the area of the weld joint. Torsional loads at failure were at least 90% of the unwelded base material. Although a wide range of voltage settings resulted in high-strength welds, typically a narrow range of voltages yielded optimal ductility. PMID- 2888305 TI - Favorable effects of sulfasalazine on small bowel Crohn's disease: a long-term study. AB - Due to conflicting reports in the literature regarding the efficacy of sulfasalazine for Crohn's disease (CD) involving small bowel alone, we reviewed the treatment results of our systematic sulfasalazine treatment in CD over a 23 yr period. We identified 28 patients with CD of small bowel alone treated between 1 and 23 yr by means of sulfasalazine alone and who went into complete clinical remission. Of these, 12 also showed total regression of radiographic abnormalities, 12 showed partial regression, while four patients still await radiographic reexamination. While our data do not permit a precise estimate, it seems that about 25% of patients with small bowel CD respond to sulfasalazine alone. Reasons are discussed why our data are at variance with some and in accord with other reports. While our study of necessity could not be carried out in double-blind fashion, patients served as their own controls, having previously failed to respond to other treatment modalities or no treatment. We conclude that sulfasalazine should be tried in the treatment of CD of small bowel because of its relatively low toxicity and reasonably high efficacy. PMID- 2888306 TI - Erythrocyte-oxidized glutathione transport in pyrimidine 5'-nucleotidase deficiency. AB - The oxidized form of glutathione transport was studied in human erythrocytes in pyrimidine 5'-nucleotidase (P5N) deficiency, a disorder in which the amounts of CTP and UTP in the erythrocytes are elevated. The inhibition of ATP-requiring oxidized glutathione (GSSG) transport by CTP and UTP is believed to play a role in elevating the levels of the reduced form of glutathione (GSH) in the erythrocytes of patients with P5N deficiency. The current investigation was undertaken to determine if GSSG transport actually decreases in the erythrocytes of such patients. Erythrocytes from a 17-year-old patient and a 13-year-old patient with P5N deficiency hemolytic anemia and from ten normal subjects were used as materials for the experiment. Erythrocytes, which had been previously incubated with [3H]glycine, were incubated at 37 degrees C, and the rate of [3H]GSSG transported by the cells was estimated. The velocity of GSSG transport out of the erythrocytes was quite low in the patients, 3.17-3.65 nmol GSSG/ml erythrocytes/hr at 37 degrees C in one case, and 3.30 nmol GSSG/ml erythrocytes/hr in the other case, vs that in the normal controls (6.00 +/- 0.80 nmol GSSG/ml erythrocytes/hr; mean +/- SD). The activity of gamma glutamylcysteine synthetase and glutathione synthetase did not decrease in the patients. Decreased transport activity of GSSG in addition to a normal synthesis rate for GSH may explain the increased concentration of erythrocyte GSH in P5N deficiency. PMID- 2888307 TI - Diminished lymphocyte and granulocyte gamma-glutamyltranspeptidase activity in acute lymphocytic leukemia and response to chemotherapy. AB - gamma-Glutamyltranspeptidase (GGT) activity (per mg protein) in blood lymphoid cells of 27 children with acute lymphoblastic leukemia (ALL) (1.05 +/- 0.15) was significantly below that of controls (2.25 +/- 0.30), became normalized during chemotherapy-induced remission (2.47 +/- 0.26), and was low again (1.59 +/- 0.62) in relapsed subjects. Individual variations in the GGT activity of the blood lymphoid cell fraction (per mg protein) bore a significant inverse correlation to the number of white blood cells (WBC) as well as of blasts per ml blood. Blasts had minimal GGT activity; however, partial GGT deficiency was also exhibited by the microscopically normal circulatory lymphocytes of several patients prior to treatment and in relapsed subjects whose blood was still devoid of blasts. Significantly diminished GGT activity (per mg protein) was found in the blood granulocytes of ALL subjects. This deficit, restored during remission and present again at relapse, varied in magnitude but showed no statistically significant correlation to the different patients' degree of neutropenia. In about one-third of the newly diagnosed or relapsed pre-B ALL children, the circulatory granulocytes' GGT activity was only 10-20% of normal. The results suggest that 1) the presence or absence of this sign of functional maldifferentiation in granulocytes is a factor in the heterogeneity of disease manifestation among subjects with apparently the same type of ALL and that 2) measurement of GGT in the circulatory granulocytes, as well lymphocytes, may be useful for monitoring the efficacy of chemotherapy. PMID- 2888309 TI - Update on secondary forms of hyperparathyroidism. AB - Recent information has shed a new light on the control of parathyroid hormone (PTH) secretion by calcium and 1,25-(OH)2D. These new data have permitted a better understanding of the pathogenesis and management of secondary hyperparathyroidism in end-stage renal disease. Emerging evidence has suggested a role for secondary hyperparathyroidism in the development of certain forms of hypertension and osteoporosis. Recent insights have been obtained regarding the occurrence of secondary hyperparathyroidism in obese and black subjects, in patients with multiple endocrine neoplasia type I, and in manic-depressive patients receiving lithium therapy. This review examines some of these recent gains in knowledge concerning secondary hyperparathyroidism, as well as their clinical implications. PMID- 2888308 TI - Molecular analysis of a polymorphic domain of alpha satellite from the human X chromosome. AB - Alpha satellite DNA, a diverse family of tandemly repeated DNA sequences located at the centromeric region of each human chromosome, is organized in a highly chromosome-specific manner and is characterized by a high frequency of restriction-fragment-length polymorphism. To examine events underlying the formation and spread of these polymorphisms within a tandem array, we have cloned and sequenced a representative copy of a polymorphic array from the X chromosome and compared this polymorphic copy with the predominant higher-order repeat form of X-linked alpha satellite. Sequence data indicate that the polymorphism arose by a single base mutation that created a new restriction site (for HindIII) in the sequence of the predominant repeat unit. This variant repeat unit, marked by the new HindIII site, was subsequently amplified in copy number to create a polymorphic domain consisting of approximately 500 copies of the variant repeat unit within the X-linked array of alpha satellite. We propose that a series of intrachromosomal recombination events between misaligned tandem arrays, involving multiple rounds of either unequal crossing-over or sequence conversion, facilitated the spread and fixation of this variant HindIII repeat unit. PMID- 2888310 TI - A new DNA probe proximal to and closely linked to fragile X. PMID- 2888311 TI - Chromosome 20 deletion in multiple endocrine neoplasia type 2: expanded double blind studies. AB - Multiple endocrine neoplasia (MEN) type 2A and 2B are autosomal dominant syndromes in which medullary thyroid cancers are associated with adrenal pheochromocytomas. We have expanded our double-blind studies of high-resolution G banded chromosomes from lymphocytes to a total of 12 MEN-2A families, 7 MEN-2B (mucosal neuroma phenotype) families and 23 non-MEN control subjects. Eighteen of 23 different control subjects were scored as having normal chromosomes 20, and 15 of 21 MEN-2A and 4 of 8 MEN-2B patients were scored as having an interstitial deletion: del(20) (p12.2p12.2). These findings suggest that the dominant mutation in many MEN-2A and MEN-2B families is a visible deletion within band 20p12.2. Combining the results of these double-blind studies with those of the only other comparable reported double-blind series provides a statistical probability of less than 1/1000 that the association between MEN-2A and the deletion was observed by chance alone. However, the occasional discrepancies in classification using presently available techniques preclude the use of high resolution chromosome studies for the diagnosis of MEN-2. PMID- 2888313 TI - Dependence on multivalent cations of quantal release of transmitter induced by black widow spider venom. AB - Application of alpha-latrotoxin (alpha-LT), the active component of black widow spider venom (BWSV), to a vertebrate neuromuscular junction, in the presence of millimolar bath concentrations of Ca2+ or Mg2+, greatly increases the frequency of miniature end-plate potentials (Fmepp). We have further characterized the cation dependence of alpha-LT action at the frog cutaneous pectoris neuromuscular junction. The divalent cations, Ca, Sr, Ba at less than or equal to 50 microM, Zn, Mn, Cd at greater than or equal to 50-100 microM, and Mg at greater than or equal to 1.0 mM, as well as the trivalent cation La at greater than or equal to 15 microM, all increase Fmepp exponentially to greater than or equal to 100-200 s 1 over several minutes time. The exponential rate of rise is graded with extracellular cation concentration and can be reduced by increasing [K+] of the bath from 2 to 25-40 mM. Long-term exposure to alpha-LT in the presence of Sr2+ or Mn2+ results in the exhaustion of the releasable quantal store of transmitter, which in the case of Mn2+ correlates well with depletion of synaptic vesicles. These data support the hypothesis that BWSV promotes an increase in Fmepp by increasing nerve terminal permeability to multivalent cations that enter the nerve terminal down their electrochemical gradients and then may bind to quantal release activating sites or displace Ca2+ from intracellular stores. PMID- 2888314 TI - Inhibitory action of peptide YY on gastric acid secretion. AB - The purpose of this study is to investigate the effect of peptide YY (PYY) on pentagastrin-, histamine-, and bethanechol-stimulated gastric acid secretion and the possible mechanisms by which PYY inhibits gastric acid secretion. Six mongrel dogs with chronic gastric and duodenal fistulas were given an intravenous infusion of pentagastrin (0.5 microgram . kg-1 . h-1), histamine (18 micrograms . kg-1 . h-1), or bethanechol (80 micrograms . kg-1 . h-1) either alone or simultaneously with intravenous PYY (100, 200, 400, pmol . kg-1 . h-1). PYY (100, 200, 400 pmol . kg-1 . h-1) inhibited pentagastrin-stimulated gastric acid secretion in a dose-dependent manner. PYY (400 pmol . kg-1 . h-1) did not depress bethanechol-stimulated gastric acid secretion. PYY (400 pmol . kg-1 . h-1) also failed to inhibit histamine-stimulated gastric acid secretion. Furthermore, PYY inhibit pentagastrin-stimulated gastric acid secretion in the face of atropine, vagotomy, or indomethacin treatment. These findings indicate that the inhibitory action of PYY on gastric acid secretion is in part independent of long and short cholinergic pathways. These findings also indicate that the inhibitory mechanism of PYY is independent of prostaglandin synthesis. Our findings are discussed in relation to previous reports regarding the effects of PYY on gastric acid secretion. PMID- 2888312 TI - Differentiation of human neuroblastoma recapitulates neural crest development. Study of morphology, neurotransmitter enzymes, and extracellular matrix proteins. AB - Differentiation of human neuroblastoma (NB) was studied in vitro with five NB cell lines treated with dibutyryl cyclic adenosinemonophosphate and retinoic acid. Although the above agents induced different responses in the various cell lines, three overall morphologic phenotypes emerged: a neuronal, characterized by cell processes and neurosecretory granules, a flat cell without pigment, which displayed basal lamina pertinent to Schwann cells, and a flat pigmented cell which exhibited melanosomes, similarly to melanocytes. The activity of the Schwann cell enzyme cyclic nucleotidyl phosphohydrolase increased considerably in one condition, after induction of a predominantly flat cell phenotype. All studied NB cell lines were capable of synthesizing and expressing the extracellular matrix proteins laminin (LM), fibronectin (FN), and Type IV collagen; but a specific pattern of expression emerged after differentiation, which was proportional to normal tissue equivalents: neuronal--none; melanocytic- FN only; and Schwann cell--large amounts of FN, LM, and Type IV collagen. PMID- 2888315 TI - Coupling of guanine nucleotide inhibitory protein to somatostatin receptors on pancreatic acinar membranes. AB - Guanine nucleotides and pertussis toxin were used to investigate whether somatostatin receptors interact with the guanine nucleotide inhibitory protein (Ni) on pancreatic acinar membranes in the rat. Guanine nucleotides reduced 125I [Tyr1]somatostatin binding to acinar membranes up to 80%, with rank order of potency being 5'-guanylyl imidodiphosphate [Gpp(NH)p] greater than GTP greater than GDP greater than GMP. Scatchard analysis revealed that the decrease in somatostatin binding caused by Gpp(NH)p was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. The inhibitory effect of Gpp(NH)p was partially abolished in the absence of Mg2+. When pancreatic acini were treated with 1 microgram/ml pertussis toxin for 4 h, subsequent 125I-[Tyr1]somatostatin binding to acinar membranes was reduced. Gpp(NH)p further decreased somatostatin binding to islet-activating protein (IAP) treated acinar membranes. Pertussis toxin treatment also abolished the inhibitory effect of somatostatin on vasoactive intestinal peptide-stimulated increase in cellular content of adenosine 3',5'-cyclic monophosphate (cAMP) in the acini. Furthermore, exposure of acini to IAP caused ADP ribosylation of a membrane protein with Mr = 41,000 in parallel to the inhibition of cAMP accumulation in acini. The present results suggest, therefore, that 1) somatostatin probably functions in the pancreas to regulate adenylate cyclase enzyme system via Ni, 2) the extent of modification of Ni is correlated with the ability of somatostatin to inhibit cAMP accumulation in acini, and 3) guanine nucleotides also inhibit somatostatin binding to its receptor. PMID- 2888316 TI - Alterations of enzymatic activities along rat collecting tubule in potassium depletion. AB - This study was designed to correlate morphological alterations induced in rat collecting tubule by potassium depletion with changes in the activity of enzymatic markers of the cell basolateral membrane. Results show the following responses. 1) Potassium depletion induced a huge and progressive hypertrophy of the outer medullary collecting tubule (MCT). Hypertrophy was paralleled by enhancements of vasopressin- and forskolin-dependent adenylate cyclase (AC) activities. Glucagon-sensitive AC was also increased, but with a different kinetics, whereas isoproterenol-dependent AC was only modestly stimulated. 2) In cortical (CCT) and papillary collecting tubules, AC response to hormones did not change. The concentrating defect of K-deprived rats, therefore, does not appear to result from an intrinsically defective adenylate cyclase system in any portion of the collecting tubule. Decreased AC response of the medullary thick ascending limb to vasopressin and glucagon, observed after 3-5 wk of K depletion, might account, at least in part, for reduced hypertonicity of medullary tissue. 3) Na+ K+-ATPase activity fell in CCT, probably in relation to decreased K secretion. Conversely, in MCT, Na+-K+-ATPase rose much more than tubular volume. The physiological significance of this latter observation remains to be established. PMID- 2888317 TI - AVP-induced pulmonary vasodilation during specific V1 receptor block in conscious dogs. AB - Our objectives were 1) to determine whether exogenously administered arginine vasopressin (AVP) can exert a vasoactive influence on the pulmonary circulation of conscious dogs during specific vasopressinergic-1 (V1) receptor block, and 2) to assess the extent to which the pulmonary vascular response to AVP during V1 receptor block is mediated by either sympathetic beta-adrenergic or cholinergic receptor activation or by cyclooxygenase pathway activation. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by stepwise constriction of the thoracic inferior vena cava to reduce Q. In dogs pretreated with a specific V1 receptor antagonist [d(CH2)5 AVP, 10 micrograms/kg iv], AVP infusion (7.6 ng.kg-1 X min-1 iv) increased (P less than 0.01) Q from 139 +/- 6 to 175 +/- 8 ml.min-1 X kg-1, and decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure pulmonary capillary wedge pressure: PAP-PCWP) over the entire range of Q studied (140 to 80 ml.min-1 X kg-1). This pulmonary vasodilator response to AVP during V1 block was also observed following sympathetic beta-adrenergic block alone, following combined sympathetic beta-adrenergic and cholinergic block, and following cyclooxygenase pathway inhibition. Thus exogenous administration of AVP during specific V1 receptor block results in active, nonflow-dependent pulmonary vasodilation. This pulmonary vasodilator response is not mediated by reflex activation of sympathetic beta-adrenergic or cholinergic receptors or by metabolites of the cyclooxygenase pathway over a broad range of Q. PMID- 2888318 TI - Central opioid mechanisms and cardiovascular control in hemorrhagic hypotension. AB - Bleeding volume during standardized hemorrhagic hypotension was studied in anesthetized, artificially ventilated rats after specific stimulation or blockade of opiate receptor systems. Hypotension was produced by stepwise bleeding to 80, 60, and 40 mmHg systemic arterial pressure. Subcutaneous administration of morphine 15 min before the bleeding resulted in a decrease, whereas subcutaneous administration of naloxone resulted in a significant increase in the required bleeding volume. Intracerebroventricularly administered met-enkephalin, dynorphin, or specific antisera against these peptides caused no characteristic alterations of the bleeding volume although met-enkephalin and dynorphin caused a significant decrease at the 40 mmHg level. Bleeding volume, however, was markedly reduced when beta-endorphin was intracerebroventricularly administered and significantly elevated by intracerebroventricular administration of a diluted beta-endorphin antiserum. These data suggest that 1) opioid mechanisms are participating in the control of blood pressure and of bleeding volume during blood loss, 2) these control mechanisms might be activated centrally, and 3) beta endorphin or a closely related peptide plays a major role in these control mechanisms. PMID- 2888319 TI - Functional significance of alpha-adrenergic receptors in mature coronary collateral circulation of dogs. AB - There is little information on the functional significance of alpha-adrenergic receptors in the dog's coronary collateral circulation. Accordingly, we investigated the effects of infusion of either norepinephrine (NE) or B-HT 920 (BHT), an alpha 2-adrenergic agonist, on vascular resistance of coronary collaterals in chloralose-anesthetized dogs 2-3 mo after placement of an Ameroid constrictor around the left circumflex coronary (LCX) artery. To accomplish this, the vagotomized left ventricle was autoperfused through the left main coronary ostium using a servo-controlled constant-pressure pump. Pressures of the left anterior descending (LAD) and peripheral LCX arteries were measured, and regional blood flow in LAD and LCX regions were determined with radioactive microspheres before and during NE infusion in the unblocked condition, following beta adrenergic and beta + alpha 1-adrenergic blockade with the use of propranolol and prazosin, respectively. The same parameters were also measured before and during BHT infusion following beta-adrenergic and beta + alpha 2-adrenergic blockade with the use of propranolol and idazoxan, respectively. In the unblocked condition, NE reduced LAD, LCX, and collateral resistance by 43, 50, and 31%, respectively. After beta-adrenergic blockade, NE increased LAD resistance (29%) but did not alter LCX or collateral resistance. The increase in LAD resistance was abolished following alpha 1-adrenergic blockade. BHT increased vascular resistance in LAD, LCX, and collateral circulations by 35, 29, and 45%, respectively. Selective alpha 2-adrenergic blockade significantly attenuated the vasoconstrictor response to BHT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888321 TI - Clinical nonrecognition of neuroleptic-induced movement disorders: a cautionary study. AB - Extrapyramidal side effects are a major limitation in the use of neuroleptics, and tardive dyskinesia is a special public health problem. Accurate clinical diagnosis of extrapyramidal syndromes is necessary for effective management. The authors compared clinicians' recognition of the major extrapyramidal syndromes in 48 psychotic inpatients with independent blind diagnoses by clinical researchers using standardized ratings. The major finding was a high rate of clinical underrecognition of all major extrapyramidal syndromes, especially tardive dyskinesia. The authors discuss the clinical predictors of nonrecognition of extrapyramidal side effects and recommend improved training in their detection. PMID- 2888322 TI - Behavioral aspects of panic disorder. AB - The behavioral approach to panic disorder distinguishes between agoraphobia and nonsituational panic and emphasizes the handicap to the patient caused by avoidance of agoraphobic situations. Agoraphobia is a more viable label than panic disorder. Behavioral treatment consists of delineating the patient's agoraphobic avoidance and panic profile and developing a self-exposure program to produce habituation. Systematic exposure to agoraphobic situations is usually of durable efficacy, and the treatment requires little time from clinicians. Antidepressant drugs, which do not interfere with exposure, are a useful addition when dysphoria is present, but they can have troublesome side effects. PMID- 2888320 TI - A role for the ventral surface of the medulla in regulation of nasal resistance. AB - Nasal resistance is known to be affected by changes in nasal blood volume and hence to depend on sympathetic discharge to nasal blood vessels. Structures located superficially near the ventrolateral surface of the medulla significantly affect respiratory and sympathetic activity and the tone of the trachea. To assess the importance of these structures on nasal patency, we measured transnasal pressure at a constant flow and examined the change in pressure produced by topically applied N-methyl-D-aspartic acid (NMDA). Experiments were performed in chloralose-anesthetized, paralyzed, and artificially ventilated cats. NMDA administered on the intermediate area of the ventral surface of the medulla decreased transnasal pressure and increased phrenic nerve activity. The response to NMDA could be diminished or abolished by application to the ventral medullary surface of the NMDA antagonist 2-amino-5-phosphonovalerate (2-APV) or the local anesthetic lidocaine. Carotid sinus denervation and posthypothalamic decerebration did not alter the nasal and phrenic nerve responses to NMDA; however, cervical sympathetic denervation decreased these responses, both in intact and in bilaterally adrenalectomized animals. Therefore, activation of NMDA receptors on structures near the ventral surface of the medulla increases tone in the nasal vasculature and leads to a response pattern that includes changes in not only phrenic nerve activity and blood pressure but also nasal patency. PMID- 2888323 TI - Pindolol and propranolol in neuroleptic-induced akathisia. PMID- 2888324 TI - Informed consent for neuroleptics and other psychotropic agents. PMID- 2888325 TI - Misuse and abuse of benzodiazepines. PMID- 2888326 TI - [Bone cement. Materials, clinical experiences, further developments]. PMID- 2888327 TI - [Stability of cement coatings]. PMID- 2888328 TI - [Adhesion of methylmethacrylate to bones]. PMID- 2888329 TI - [Stress-induced structural changes in bone cement--studies of reoperated preparations]. PMID- 2888331 TI - [Adhesive strength of metal/bone cement compounds and bone cement/spongioid bones]. PMID- 2888330 TI - [Goals, results and consequences of long-term studies of the biochemical composite system Prosthesis, Cement. Bones of the hip]. PMID- 2888333 TI - [Standardization of bone cements]. PMID- 2888332 TI - [Penetration behavior of bone cement into the spongiosa of the marrow cavity in implantation of a prosthesis shaft in the tibia]. PMID- 2888334 TI - [Processing technics and their effects--manual processing of bone cements: mixing technics, error-free use, dangers of erroneous handling]. PMID- 2888336 TI - The effect of mixing technique and surgical technique on the properties of bone cement. PMID- 2888335 TI - [Injectable use of PMMA bone cements]. PMID- 2888337 TI - [Use of polymethylmethacrylate in medicine--a historical review]. PMID- 2888338 TI - [Effect of lamination and blood inclusions on the hardness of testing bodies of various cements]. PMID- 2888339 TI - [Electronic time control of cement processing]. PMID- 2888340 TI - [Tissue reaction to bone cement]. PMID- 2888341 TI - [Bone and border zone changes in the use of bone cements--long-term studies of human biopsy, surgical and autopsy material]. PMID- 2888342 TI - [Synthesis and composition of common bone cements]. PMID- 2888343 TI - [Tissue damage caused by PMMA bone cement]. PMID- 2888344 TI - [Interactions between roentgen contrast media of bone cements and endogenous tissues and body fluids]. PMID- 2888345 TI - [Effect of roentgen contrast media in bone cements on connective tissue and bone structures]. PMID- 2888346 TI - [Disorders of the blood supply in the femur following the cementing of endoprostheses--a study in dogs]. PMID- 2888347 TI - [Animal experiments in the assessment of tolerance to bone cements]. PMID- 2888348 TI - [Experimental testing possibilities of the morphology and mechanics of the bone cement boundary zone]. PMID- 2888349 TI - [Different changes in the calcar femoris in cemented and cement-free hip endoprostheses]. PMID- 2888350 TI - [Embolisms from the bone marrow canal following implantation of intramedullary femur head endoprostheses with polymethylmethacrylate]. PMID- 2888351 TI - [MMA toxicity versus implantation embolisms: clinical studies]. PMID- 2888352 TI - [Testing requirements of bone cements]. PMID- 2888353 TI - [Pathogen spectrum in infections following total endoprostheses]. PMID- 2888354 TI - [Comparative evaluation of the effectiveness of various antibiotics in infected total endoprostheses]. PMID- 2888355 TI - [Kinetics of the liberation of antibiotics from bone cements--results of comparative studies in vitro and in vivo]. PMID- 2888356 TI - [Antibiotics and bone cements--local therapeutic significance]. PMID- 2888357 TI - [Clinical aspects of antibiotic administration in bone cements]. PMID- 2888359 TI - [Properties of bone cements in the plastic phase: viscosity, wetting property, flow behavior, penetration]. PMID- 2888360 TI - [Clinical experiences with long-term implantation of bone cement beads containing antibiotics in bone infections]. PMID- 2888358 TI - [Long-term clinical study of antibiotic administration in bone cements (follow-up of Balgrist cases)]. PMID- 2888361 TI - [Use and experiences with gentamycin-PMMA chains in 500 cases of osteitis over a 7-year period]. PMID- 2888362 TI - [Critical remarks on local and preventive use of antibiotics]. PMID- 2888364 TI - [Can use of gentamycin-Palacos lead to the occurrence of a toxic serum gentamycin level? Drug monitoring with enzyme immunoassay]. PMID- 2888363 TI - [Side effects of gentamycin following implantation of PMMA containing gentamycin in the form of bead chains]. PMID- 2888365 TI - [Failures in the use of Nebacetin-Sulfix 6]. PMID- 2888366 TI - [Experiences with bone cement containing Nebacetin]. PMID- 2888367 TI - [Effects of Nebacetin on the implant site]. PMID- 2888369 TI - [Are long-term results of cemented hip joint endoprostheses really so bad?]. PMID- 2888368 TI - [Results of 1979-1982 follow-up of Nebacetin-Sulfix 6 implanted hip and knee prostheses]. PMID- 2888370 TI - [Long-term behavior of bone cements in vivo]. PMID- 2888371 TI - [Bone cements in surface replacement of the hip joint]. PMID- 2888373 TI - [Use of bone cements for dorsal stabilization of the cervical spine]. PMID- 2888372 TI - [Use of bone cements in spinal surgery--indications, technic and personal experiences]. PMID- 2888374 TI - [PMMA in the area of the skull and spine--experiences with cements containing antibiotics and antibiotic-free cements]. PMID- 2888375 TI - [Mechanical properties of unmodified bone cements based on PMMA]. PMID- 2888376 TI - [Experimental studies on the modification of malignant bone tumor tissue by artificial cements]. PMID- 2888377 TI - [Palacos compound osteosynthesis using the autocompression plate in resection treatment of bone metastases]. PMID- 2888378 TI - [Destruction of cement casings]. PMID- 2888379 TI - [Factors in prosthesis loosening of cement-free total hip endoprostheses]. PMID- 2888380 TI - [Loosening process of the total hip endoprosthesis with special reference to the cement]. PMID- 2888381 TI - [Technic of cement removal in exchange operations with joint endoprostheses]. PMID- 2888382 TI - [Possibilities and limits of ultrasound manipulation-removal of bone cements]. PMID- 2888383 TI - [Possibilities for improving bone cements]. PMID- 2888384 TI - [New development of a bone cement which swells]. PMID- 2888385 TI - [Development of a carbon fiber-reinforced bone cement with optimized mechanical properties]. PMID- 2888386 TI - [Gentamycin liberation from the low viscosity PMMA bone cement Refobacin E flow following TEP implantation]. PMID- 2888387 TI - [Biocements as fixation and bridging materials in bones]. PMID- 2888388 TI - Hard and soft animal tissue responses to unloaded solid and porous PMMA implants and their possible clinical applications. PMID- 2888389 TI - [Mechanical properties of a metal fiber-reinforced bone cement]. PMID- 2888390 TI - [Changes in continuous vibration resistance of PMMA cement by addition of carbon fibers, apatite powder and granules and bone particles]. PMID- 2888391 TI - [Experimental studies of continuous vibration behavior of bone cements]. PMID- 2888393 TI - [Modification of the polymerization time and temperature of PMMA cement by adding carbon fibers and apatite particles]. PMID- 2888392 TI - [Theoretical experimental studies of temperature distribution at the bone-cement boundary zone in polyethylene acetabular implants, with reference to intraoperatively recorded temperature courses]. PMID- 2888394 TI - [Animal experiment histologic and biomechanical studies of tissue tolerance and adhesiveness of bone cement containing carbon fibers and apatite]. PMID- 2888395 TI - [Osseous reaction following filling of the femoral marrow cavity with carbon fiber-reinforced Sulfix 6 bone cement in the rabbit with reference to the organization of the reinforcing fibers in a polymethylmethacrylate matrix]. PMID- 2888396 TI - [Chemical and physical properties of Implast, a new bone cement]. PMID- 2888397 TI - [First clinical study with Implast bone cement]. PMID- 2888398 TI - [Clinical evaluation and initial results of a newly developed bone cement, Implast]. PMID- 2888400 TI - [Bioactive bone cement with added glass ceramic and glass fiber reinforcement- physical properties, histomorphologic findings and results of animal experiments]. PMID- 2888399 TI - [1-year clinical results with Implast bone cement--randomized comparative study with a proven bone cement]. PMID- 2888401 TI - [Stryker "Mix Evac" bone cement mixer]. PMID- 2888402 TI - [Modification of the mechanical properties of bone cements by additives and cement aging in vitro]. PMID- 2888403 TI - [Low-viscosity bone cements especially designed for injection administration in orthopedics and its evaluation in vitro]. PMID- 2888404 TI - Influence of chemical factors on maximum temperature and residual monomer in cold curing acrylic resin. PMID- 2888405 TI - [Aging behavior of bone cements--a long-term study]. PMID- 2888406 TI - [Preclinical studies of tolerance to bone cements]. PMID- 2888407 TI - [Content and chemical residues in hardened bone cements and their effect on fibroblast cultures]. PMID- 2888408 TI - [Release of methylmethacrylate from bone cement during polymerization in bone marrow]. PMID- 2888409 TI - [Release of rest monomers and N,N-dimethyl-p-toluidine from bone cements during aging and long-term placement--an in vitro study]. PMID- 2888411 TI - [Toxicity of bone cement components]. PMID- 2888410 TI - [Pharmacologic effects and kinetics of methylmethacrylate monomers]. PMID- 2888412 TI - [Carcinogenicity and toxicology of components of methylmethacrylate bone cements]. PMID- 2888413 TI - [Quincke edema following use of bone cement in a dialysis patient: a sequela of ethylene oxide allergy?]. PMID- 2888414 TI - [Mechanical properties in micro areas of the implant site of hip joint endoprostheses]. PMID- 2888415 TI - Structure and function of mitochondria: their organization and disorders. AB - In this lecture, recent advances in studies on the structure and function of mitochondria were reviewed. In particular, in order to understand the etiology of mitochondrial myopathies, the mechanism of the biogenesis of the mitochondrial structure with proteins synthesized in mitochondria and in the cytoplasm was discussed; namely, how proteins encoded by mitochondrial DNA are biosynthesized, and how nuclealy encoded proteins are targeted into the appropriate compartments inside the mitochondria. Recent advances in mitochondriology have made it possible to isolate and purify the enzyme complexes and their subunits, which are involved in mitochondrial oxidative phosphorylation. Immunochemical analyses using a specific antibody against each complex or subunit enabled us to detect defects in individual subunits in mitochondria isolated from a small amount of biopsied material. Several examples of molecular defects revealed by these methods in patients with mitochondrial myopathies were presented, and the principles of their therapy are discussed on the basis of the pattern of the defect. Specific antibodies are also a powerful tool for the cloning of the human cDNAs for the subunits in the mitochondrial energy-transducing machinery. This approach will hopefully facilitate elucidation of the genetic defects underlying these disorders. PMID- 2888416 TI - Gene rearrangements in lymphoma. Applications to dermatopathology. AB - Clonality is regarded as an important diagnostic feature of B-cell lymphomas, but until recently the clonality of T-cell proliferations could not be directly determined. Elucidation of the genetic events in lymphocytic differentiation has led to the development of an assay for clonality in both B- and T-cell infiltrates. Clonal rearrangement of the immunoglobulin or T-cell receptor genes can be detected by the Southern blot technique. Such rearrangements provide evidence of clonal proliferation, which, in the proper context, can be regarded as a sign of malignancy. The presence of gene rearrangements in poorly differentiated neoplasms may serve as evidence of hematopoietic differentiation, and the pattern of such rearrangements may point to either T- or B-cell lineage. Specific applications to dermatopathology include the evaluation of skin biopsy specimens for cutaneous lymphoma, evaluation of peripheral blood specimens for detection of Sezary's syndrome, and evaluation of lymph nodes and blood for the staging of mycosis fungoides. PMID- 2888417 TI - [Effect and side effects of oral morphine, lormetazepam and placebos as premedication]. AB - In 60 patients undergoing a curettage in thiopentone induced inhalation anaesthesia with enflurane and N2O/O2 = 2:1, the effects of oral premedication (2 h before anaesthesia) with 30 mg morphine (MST 30) (n = 21), 1 mg lormetazepam (Noctamid) (n = 19) and placebo (n = 21) on psychological (anxiety, depression and asthenia), physiological (blood pressure, heart and respiratory rate) and pain parameters (visual analogue scale, analgesic consumption) were investigated. The study design was single blind, randomized. Before premedication the three groups did not differ in one parameter and so were comparable. MST 30 had a significantly better anxiolytic, Lormetazepam a significantly better antidepressive effect than the compared substance. There were no differences in blood pressure and heart rate. In contrast to lormetazepam and placebo after MST 30 there was no increase in the respiratory rate which can be explained by the anxiolytic stress reducing effect. There was no difference in peri- and intraoperative pain parameters, probably due to the type of surgery. Nausea and vomiting occurred more frequently after MST 30, but there was no significance. A higher rate was probably prevented by the application of transdermal scopolamine the day before surgery. The indication of analgesics (opiates) for premedication is discussed taking the controversy into account. The results of this study show that oral morphine (MST 30) has an anxiolytic effect, one of the most important effects a premedication should have. Further studies should investigate in which types of surgery the analgesic effect of MST 30 is peri- and intraoperatively relevant, so that advantages compared to e.g. Flunitrazepam, Midazolam or Lormetazepam in a higher dosage could be expected. PMID- 2888418 TI - [Comparative study of the effect of muscle relaxants on the intraocular pressure]. AB - Control of intraocular pressure is a major concern in ophthalmic anesthesia, especially in the presence of glaucoma or penetrating eye injury. The use of succinylcholine under these conditions is controversial. This study was undertaken to assess the effects of the neuromuscular blocking agents succinylcholine, pancuronium, metocurine, vecuronium, and atracurium on the intraocular pressure of dogs. The study was performed on five "conditioned" mature male foxhounds. The dogs were intubated immediately after induction with thiopental 10 mg/kg and ventilated with an O2/N2O mixture (FIO2 = 0.33). The ventilation was controlled to maintain an endtidal CO2 concentration of 5 vol.%. and anesthesia maintained with a fentanyl infusion of 10 micrograms/kg per hour. Direct and continuous measurements were taken of blood pressure (MAP), central venous pressure (CVP), and intra-ocular pressure (IOP), the latter via a 22-gauge needle inserted into the anterior chamber of the eye. A force-displacement transducer was attached to the hindpaw to monitor muscle twitch following supramaximal stimulation of the anterior tibial nerve. These four measurements were displayed on a multi-channel polygraph (Figs. 1 and 2). Control values were obtained and then succinylcholine 1 mg/kg, pancuronium 0.1 mg/kg, metocurine 0.3 mg/kg, vecuronium 0.1 mg/kg, or atracurium 0.4 mg/kg were given in a randomized fashion and on different days. Measurements of heart rate (HR), MAP, CVP, and IOP were noted at 2, 5, 10, 20, and 30 min after giving the neuromuscular blocking agent. The results, as displayed on the polygraphy, indicate that the least effect on IOP and cardiovascular state followed neuromuscular blockade with vecuronium and atracurium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888419 TI - Immunocytochemical demonstration of gastric endocrine cells in the stomach gland patch of the koala, Phascolarctos cinerus. AB - The relative frequency and topographical distribution of endocrine cells containing gut hormones were studied by immunocytochemistry in the stomach gland patch of the koala. Numerous somatostatin- and a moderate number of bovine pancreatic polypeptide-immunoreactive cells were found primarily in the lower two thirds of the oxyntic glands. 5-hydroxytryptamine-immunoreactive cells were few in number and scattered throughout these glands. Glucagon-immunoreactive cells were observed only rarely and then were confined to the basal region of the oxyntic glands. PMID- 2888420 TI - [Male infertility in Tunisia: apropos of 373 cases]. AB - The results of a study of 373 cases of male sterility in Tunisia are presented. Factors with negative effects on fertility are listed according to their incidence: hypogonadism, gonococci infection, following varicocele and excessive smoking. Important is; early diagnosis of venereal disease and its effective treatment; examination and treatment of men with cryptorchism (systematic examination of genital organs in childhood); availability of necessary technical means for the detection of varicoceles; finally the diagnosis and treatment of immunologic sterility factors. PMID- 2888421 TI - Analgesic and cardiorespiratory effects of epidural sufentanil and morphine in humans. AB - Thirty patients undergoing abdominal surgery were randomly assigned postoperatively into two groups for a double-blind evaluation of the analgesic potency and cardiorespiratory effects of either 50 micrograms sufentanil or 5 mg morphine injected epidurally. After sufentanil injection, good postoperative analgesia was obtained, with a linear analog score (LAS) of less than 5 starting 5 min after injection and lasting for more than 6 hr. Linear analog scores obtained during coughing (LASC) and during movement (LASM) were less than 5 after 10 min and lasted for more than 4 hr. Respiratory rate decreased significantly for 2 hr after sufentanil injection. After morphine, pain relief started after 20 min and lasted for more than 12 hr. Respiratory rate decreased after 30 min. Sedation was greater after sufentanil than after morphine. PaCO2, which increased significantly 1 hr after sufentanil, did not change after morphine. Peak expiratory flow significantly improved for 2 hr after both sufentanil and morphine, whereas forced vital capacity improved for 4 hr after sufentanil and 8 hr after morphine administration. Forced expiratory volume did not change with either drug. It is concluded that 5 mg morphine injected epidurally provides longer lasting analgesia than does 50 micrograms sufentanil, but that in the first hours analgesia is better after sufentanil. Injection of either drug was accompanied by remarkable cardiovascular stability. PMID- 2888422 TI - Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. V. Role of pharmacokinetics and the autonomic nervous system in the interactions between verapamil and inhalational anesthetics. AB - To assess the role of both pharmacokinetics and the autonomic nervous system in the interaction between inhalational anesthetics and verapamil, dogs were chronically instrumented to measure heart rate, PR interval, dP/dt, cardiac output, and aortic blood pressure. In a first group of seven dogs, studied awake and during halothane (1.2%), enflurane (2.5%), and isoflurane anesthesia (1.6%), verapamil was infused for 30 min in doses calculated to obtain similar plasma concentrations (83 +/- 10, 82 +/- 6, 81 +/- 10, and 77 +/- 9 ng.ml-1, respectively). For the latter purpose, the infusion dose was 3 and 2 micrograms.kg-1.min-1 awake and during anesthesia, respectively, preceded by a loading dose of 200, 150, and 100 micrograms.kg-1, awake, during isoflurane, and halothane and enflurane, respectively. In awake dogs, verapamil induced an increase in heart rate (24 +/- 5 bpm) and PR interval (35 +/- 9 msec) and a decrease in mean arterial pressure (-5 +/- 2 mmHg) and dP/dt (-494 +/- 116 mmHg/s). Although plasma concentrations were similar in awake and in anesthetized dogs, the only statistically significant changes induced by verapamil were an increase in heart rate and a decrease in dP/dt during halothane and enflurane, while left atrial pressure increased only with enflurane. In a second group of six dogs, verapamil pharmacokinetics were determined in the presence and absence of a ganglionic blocking drug (chlorisondamine, 2 mg.kg-1 iv). Blockade of ganglionic transmission resulted in a decrease in both initial volume of distribution and total clearance of verapamil--changes similar to those previously reported with inhalational anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888423 TI - Prolongation of QT interval in association with the administration of large doses of opiates. PMID- 2888424 TI - Comparative study of the peripheral and central effects of terfenadine and cetirizine 2 HCl. AB - The histamine cutaneous reactivity of healthy volunteers was measured after a single oral intake of placebo, terfenadine 60 mg and 180 mg, and cetirizine 2 HCl 10 mg. Central side effects were evaluated by Visual Analog Scales for drowsiness and movement coordination. The anti-H1 cutaneous effect of cetirizine 2 HCl proved to be significantly more rapid, more pronounced, and longer lasting than that of terfenadine 60 mg. Cetirizine and terfenadine 180 mg were equipotent. The Visual Analog Scales for central nervous system effects did not show any difference between cetirizine, terfenadine, and placebo. PMID- 2888426 TI - Bluetongue and epizootic hemorrhagic disease in white-tailed deer from Oklahoma: serologic evaluation and virus isolation. AB - Blood samples were collected from 194 white-tailed deer from 27 locations in Oklahoma from 1977 through 1984. Sixty-eight (35%) of the deer had antibody against bluetongue virus (BTV) and 78 (40%) had antibody against epizootic hemorrhagic disease virus. Seropositive deer were detected in each of the 4 geographic quadrants of the state. Virus isolation was attempted in 40 deer from the northeast quadrant of Oklahoma (1983 through 1984); BTV was isolated from 11 deer, but epizootic hemorrhagic disease virus was not isolated. The isolation of BTV serotype 11 from these deer from 1983 through 1984 coincided with reported isolations of this serotype in other ruminants in Oklahoma during this time. PMID- 2888425 TI - Jellyfish envenomation syndromes updated. AB - Jellyfish venoms are mixtures of toxic and/or antigenic polypeptides and enzymes pathogenic to human beings. As newer therapeutic agents become available to treat the various reactions to stings caused by these animals, an accurate diagnosis of the type of reaction the patient experiences and of the offending species will be necessary. Fatal reactions may be caused either by anaphylaxis or by the action of toxins in the venom on the heart, respiratory center, or kidneys. Cutaneous eruptions after envenomation may be local, generalized, exaggerated, recurrent, delayed, persistent, or occur at sites distant from the primary sting. Fat atrophy, pigmentary changes, vasospasm, and contractures with gangrene can occur after jellyfish stings. Identification of the envenoming animal can be made by actual visualization, examination for nematocysts on skin scraping, or serologically. It may also be predicted based on knowledge of location, time, and environmental circumstances of the encounter. First-aid measures designed to prevent additional nematocyst rupture are species-specific. Anaphylaxis should be prevented by the appropriate lifesaving measures. Other syndromes, caused by the toxins of the venom or mediated by humoral or cellular immune mechanisms, should be treated specifically. PMID- 2888427 TI - Life-threatening water intoxication during somatostatin therapy. PMID- 2888428 TI - Frequency modulation dynamics in neural networks. AB - The VCON model described here shares certain qualitative features of stimulus response characteristics with the data in FIGURE 1 and TABLE 1. At the same time, it provides an uncomplicated methodology for modelling neural networks that emphasizes their frequency aspects. In particular, models based on VCONs are amenable to the rotation vector method, which can be used to uncover stable synchronization of firing within a network. This is described in the appendix, where it is shown that the stable firing patterns within the network correspond to minima of an associated (local) energy function. We have seen here how a model of a simple CPG for breathing can be constructed and analyzed. Similar models for rhythm splitting of small mammal activity cycles, sound location networks, and motility in the gastrointestinal tract have been constructed, and large networks of VCONs have been shown to have stable spatial patterns of synchronization. PMID- 2888429 TI - Increased reactivity to HTLV-I in inflammatory nervous system diseases. AB - The presence of IgG antibodies reacting with purified and disrupted human T lymphotropic virus type I (HTLV-I) was examined by an indirect enzyme-linked immunosorbent assay (ELISA) in sera from 49 patients with multiple sclerosis (MS), 21 patients with aseptic meningoencephalitis (AM), 12 patients with Guillain-Barre syndrome (GB), and 30 patients with tension headache (TH). This was also assessed in the concentrated cerebrospinal fluid (CSF) of most of these patients, as well as in sera of 60 blood donors (BD). Standardized amounts of serum IgG and CSF IgG were used in ELISA. For sera, higher reactivity with HTLV-I was found in all four patient groups compared with the BD group, but no significant differences were observed among the four groups. There was higher reactivity with HTLV-I in the CSF of patients with MS, AM, and GB compared to findings in patients with TH. Ten serum (2 MS, 3 GB, 3 TH, 2 BD) and 3 CSF (1 MS, 1 GB, 1 TH) specimens considered positive by ELISA for HTLV-I were found negative on confirmatory Western blot analysis. We extended this study to analyze the in vitro production of anti-HTLV-I-IgG antibodies by the 24-hour cultivation of unstimulated lymphocytes from peripheral blood and CSF of 6 additional patients with MS directly in HTLV-I antigen-coated wells of microtiter plates. This was followed by determination of specific antibodies by ELISA in the same wells. No antibody production was measurable. Our data do not favor the hypothesis of an HTLV-I-related human retrovirus in the etiology of MS. PMID- 2888430 TI - [Cytopathogenic action of intact and antibiotic-altered populations of Bordetella pertussis on a human amnion cell culture]. AB - Cytopathogenic and adhesive action of intact B. pertussis population and population changed under the effect of antibiotics was studied comparatively. It was shown that the level and character of the changes in the cell culture of line FL human amnion depended on the antibiotic used in the experiments. Populations of B. pertussis changed under the effect of tetracycline had the highest cytopathogenic and adhesive activity, while the activity of the population changed under the effect of erythromycin was the least. The decrease in the cytopathogenic and adhesive activity of B. pertussis changed under the effect of erythromycin correlated with lowering of the toxicity and the loss of the main agglutinogenic factors of the surface of the bacteria cell wall. The increase in the toxicity of the population changed under the effect of tetracycline was accompanied by changes in the cytopathogenic and adhesive properties of the culture. PMID- 2888431 TI - On the origin of the limited control of mitochondrial respiration by the adenine nucleotide translocator. AB - A thermodynamic control theory previously developed has been applied to mitochondrial oxidative phosphorylation with emphasis on the role of delta microH and coupling and within the paradigm of delocalized chemiosmotic coupling. The basis for the observed distribution of flux control over the participating enzymes is shown to lie in the relative magnitudes of so-called delta microH elasticity coefficients, i.e., the delta microH dependencies of the different mitochondrial processes. In particular the relatively strong delta microH dependence of mitochondrial respiration is responsible for the significant role of the adenine nucleotide translocator in the control of oxidative phosphorylation. Uncoupling decreases the control exerted by this translocator on respiration but increases that exerted on phosphorylation. PMID- 2888433 TI - Preparation of functional acetyl-CoA carboxylase mRNA from rat mammary gland. AB - Poly(A)+ RNA from lactating rat mammary glands was fractionated according to size by isokinetic sucrose gradient centrifugation to obtain a fraction enriched for acetyl-CoA carboxylase. In vitro translation of this RNA preparation yielded apparent full-length acetyl-CoA carboxylase with a molecular weight of 260,000. The synthesized protein was identified as acetyl-CoA carboxylase by specific immunoprecipitation. Tests with antiserum to fatty acid synthetase, revealed that the fractions containing acetyl-CoA carboxylase mRNA also contained mRNA for fatty acid synthetase; both of these mRNAs were approximately 10 kb. Fatty acid synthetase with a molecular weight of 250,000 was synthesized. Using an in vitro rabbit reticulocyte lysate translation system, we have shown that the amount of translatable acetyl-CoA carboxylase mRNA increases during lactation. On the fifth day postpartum the level of translatable acetyl-CoA carboxylase mRNA increased to a peak level seven times that on the day of parturition. PMID- 2888432 TI - Solubilization and properties of the liver plasma membrane transglutaminase. AB - We recently reported that rat liver contains a transglutaminase activity which is specifically associated with the lateral plasma membrane domain [D. J. Tyrrell, W. S. Sale, and C. W. Slife (1986) J. Biol. Chem. 261, 14833-14836]. In this manuscript, conditions for maintaining the activity of this plasma membrane associated enzyme are described and an unusual method for solubilizing the enzyme is detailed. When rat liver plasma membranes were stored at 4 degrees C, the transglutaminase activity was rapidly lost unless dithiothreitol was present. If calcium or EDTA were included with the reducing agent, a time-dependent enhancement of enzyme activity occurred. These reagents probably prevented and perhaps reversed the oxidation of critical thiol residues in the transglutaminase. When the membranes were incubated at 37 degrees C, increased enzyme activity was found only if 50% glycerol was added to the dithiothreitol and calcium-containing buffer. Under these latter conditions, a selective release of the enzyme from the membrane also occurred, with the enzyme remaining soluble after the glycerol was removed. These data, and our inability to solubilize the enzyme with detergents, indicate that the plasma membrane transglutaminase is a peripheral membrane protein which associates only with a specific plasma membrane domain. PMID- 2888434 TI - [A molecular basis for multidrug-resistance and reversal of resistance with human malignant cells]. AB - Development of cellular resistance to multiple types of anticancer agents has been recognized as one of the major obstacles for the effective cancer chemotherapy. Increased expression of mdr 1 mRNA seems to be a common mechanism for multidrug resistance (MDR) in human malignant cells. The product of the mdr 1 gene is P-glycoprotein. The predicted membrane orientation of the protein and homology with bacterial active transport proteins, and capability of the protein to bind hydrophobic anticancer agents are consistent with the function of P glycoprotein as an energy-dependent efflux pump responsible for MDR phenotype. Most of the hydrophobic agents which overcome MDR are cationic and amphipathic. These agents interact with certain polar lipids and inhibit also the binding of hydrophobic anticancer agents with P-glycoprotein. They might directly bind to the binding site of anticancer agents on P-glycoprotein and competitively inhibit the binding of anticancer agents. Alternatively, they might bind to polar lipids of membrane vesicles and indirectly inhibit the binding ability of the protein to anticancer agents by perturbing the membrane function. PMID- 2888435 TI - [A case of adult T-cell leukemia achieving complete remission with epirubicin, vincristine and prednisolone chemotherapy]. AB - A 68-year-old man was referred to our hospital because of generalized lymphadenopathy. His abnormal findings were hepatomegaly, leukocytosis and elevated serum LDH. Anti-ATLA antibody was positive. As about half of the peripheral lymphocytes reacted to the monoclonal antibody CD25, these cells were considered to be compatible with ATL cells having an interleukin-2 receptor. Initially, recombinant beta-interferon was administered, but it was not effective. A combination of vincristine (VCR) and prednisolone (PDN) was partially effective against the lymphadenopathy, but the hepatomegaly and leukocytosis did not improve. 4'-epi-Adriamycin (Epirubicin), at a doses of 20 mg/body, weekly, was subsequently added to VCR + PDN therapy. The patient achieved complete regression 2 months later, and has been in continuous complete remission for more than 3 months. PMID- 2888436 TI - T activation haemolysis and death after blood transfusion. AB - A 30 week gestation infant developed necrotising enterocolitis associated with Clostridium perfringens septicaemia at 3 weeks of age. He responded to treatment with intravenous fluids, antibiotics, and blood, but his blood haemolysed. Because of anaemia further blood was given, but, within minutes he died. Examination of his red cells showed an increase in T activation. PMID- 2888438 TI - Chloroquine-induced pruritus in Nigerian medical and nursing students. AB - Two hundred and fifty-one Nigerian medical and nursing students from the University of Maiduguri Teaching Hospital completed a questionnaire on chloroquine-induced pruritus. One hundred and thirty (51.8) students experienced itching, and in 71 the symptoms were so distressing that chloroquine was no longer used for treating febrile malarial episodes. Antihistamines taken before chloroquine or a change in the route of administration were helpful in preventing or a ameliorating symptoms in some of the students. Significantly more students with chloroquine-induced pruritus had parents or siblings similarly affected compared with students who did not get pruritus, and this supports the concept of a pharmacogenetic basis to the disorder. PMID- 2888437 TI - Histamine H1 receptors on adherent rheumatoid synovial cells in culture: demonstration by radioligand binding and inhibition of histamine-stimulated prostaglandin E production by histamine H1 antagonists. AB - Histamine H1 receptors have been demonstrated on adherent rheumatoid synovial cells using biochemical and radioligand binding assays in vitro. The addition of histamine (17.8 mumol/l) to nine primary cultures of adherent rheumatoid synovial cells resulted in a two- to 21-fold increase in the production of prostaglandin E (PGE). This increase was inhibited by three H1 receptor antagonists (mepyramine, tripelennamine, and chlorpheniramine) in a dose related manner at concentrations below 10(-6) mol/l. Competitive binding assays with [3H]mepyramine gave ED50 values of approximately 10(-5) mol/l for the three H1 antagonists. H2 receptor antagonists (cimetidine and ranitidine) did not inhibit the histamine induced increase in PGE and did not compete effectively with the binding of H1 antagonists. PMID- 2888439 TI - Plasmodium berghei-infected mice: lack of effect of meclizine and cimetidine on the development of pulmonary oedema. AB - The involvement of histaminergic mechanisms in the pathogenesis of pulmonary oedema observed in Plasmodium berghei-infected mice was investigated. Histamine concentrations in plasma and whole blood of infected and normal mice were determined by radioenzymatic assay during the seven days of the infection. Elevated plasma and whole blood histamine levels were found at the last stages of infection (sixth day and seventh day after ip injection of parasitized erythrocytes), showing a close temporal correlation between the development of oedema and the elevation of the circulating histamine concentrations. However, the treatment of infected mice with the H1- or H2-receptor antagonists, meclizine or cimetidine, did not change the development of pulmonary oedema. The absence of effects of H1- and H2-receptor blockers on this model is a suggestive evidence that histamine does not contribute to P. berghei-induced pulmonary oedema in mice. PMID- 2888440 TI - Responsiveness of skeletal muscle branches of the dog femoral artery to alpha adrenoceptor agonists before and after cold storage. AB - Using the cannula inserting method, we investigated the responsiveness of isolated skeletal muscle branches of the dog femoral artery to alpha-adrenoceptor agonists and potassium chloride, and the influence of cold storage (3 days and 5 7 days, at 4 degrees C). Epinephrine (EPI) and norepinephrine (NE) induced a marked vasoconstriction in a dose-related manner. A large dose of EPI and NE usually induced an increase in perfusion pressure of more than 100-200 mm Hg. Phenylephrine (PE) and methoxamine (MT) also induced a marked constriction, but clonidine (CLO) and xylazine (XYL) produced only a slight vasoconstriction, even in large doses. Tyramine (TYR) also induced a small vasoconstrictor response. A large dose of KCl induced a marked vasoconstriction. The order of potency of constriction was EPI greater than or equal to NE greater than PE = MT much greater than KCl greater than CLO greater than or equal to TYR greater than or equal to XYL. The vasoconstrictor responses to EPI and NE were significantly suppressed by 3-7 days of cold storage. Vasoconstrictor responses to MT were slightly suppressed by cold storage. However, XYL-, CLO- and TYR-induced vasoconstrictions were not significantly influenced by cold storage. KCl-induced constriction was clearly suppressed by cold storage. These observations suggest that the postjunctional alpha-adrenoceptor in skeletal muscle branches of the femoral artery is of the alpha 1-type. Moreover, it was shown that prolonged cold storage (3-7 days, at 4 degrees C) resulted in a decrease in sensitivity of these vessels to alpha-adrenoceptor agonists and in a marked decrease in sensitivity to KCl, suggesting a depression of the calcium channel by cold storage. PMID- 2888441 TI - The action of dopamine upon glycerol and fatty acid release by rat brown adipose tissue. AB - Dopamine was shown to be effective in releasing glycerol and nonesterified fatty acid from brown fat adipocytes. The response was inhibited by dopamine antagonists, and by a beta-blocker. This is further evidence that dopamine may be important in the release of energy from brown fat in newborn and cold-adapted animals. PMID- 2888442 TI - Pharmacological and electrophysiological analysis of the effects of nicotine on cat blood pressure. AB - Nicotine (20-60 micrograms/kg) produced an initial vasodepressor response followed by a vasopressor response in anaesthetized cats, the mechanism of which was investigated. The vasodepressor response was antagonized by atropine or by vagotomy and was potentiated by physostigmine or neostigmine. Nicotine increased the single unit activity of different peripheral sympathetic nerves and evoked contraction of nictitating membrane and spleen along with vasopressor response. The vasopressor response was antagonized by phentolamine, prazosin, guanethidine, bretylium, 6-OHDA, hemicholinium-3 or hexamethonium. Propranolol or atenolol pretreatment potentiated the vasodepressor response and was antagonized by atropine. Desensitization by salbutamol did not modify the response to nicotine. The biphasic response to nicotine remained unaltered in yohimbine pretreated, in adrenalectomized, and in acute spinal as well as in decapitated animals; intracarotid or intracerebroventricular administration of nicotine did not produce any response. The biphasic response to nicotine does not involve the stimulation of the central vasomotor centre. In conclusion, these results suggest that the vasodepressor response is due to the vagal cholinergic mechanism. The vasopressor response is a consequence of activation of different peripheral adrenergic nerves causing increased release of the adrenergic transmitter at the neuroeffector region and the alpha 1-adrenoceptor mediate vasoconstriction in the systemic vascular bed. PMID- 2888443 TI - Effects of alpha-adrenoceptor antagonists on the mydriatic and bradycardic effects of detomidine. AB - Pupillary and cardiac responses to i.v. injection of detomidine (1-30 micrograms/kg), a novel veterinary sedative analgesic, were observed in rats anesthetized with pentobarbital. Detomidine caused a dose-dependent mydriasis and bradycardia. The alpha 2-adrenoceptor antagonist, yohimbine (0.1-1.0 mg/kg, i.v.), prevented the detomidine-induced mydriasis in a dose-dependent manner. The nonselective alpha-adrenoceptor antagonist, tolazoline at 6 mg/kg, i.v., also prevented the detomidine-induced mydriasis. However, tolazoline at 3 mg/kg, i.v., was not effective in preventing this effect of detomidine. The alpha 1 adrenoceptor antagonist, prazosin at 1.5 mg/kg, i.v., did not reduce the detomidine-induced mydriasis. In contrast to what was found with mydriasis, none of the antagonists at the doses studied prevented detomidine-induced bradycardia. When yohimbine was given i.v., 5 min after the last dose of detomidine (30 micrograms/kg), it promptly and completely reversed mydriasis in all groups. However, yohimbine reversed detomidine-induced bradycardia only in the control group and in the animals pretreated with 1.5 mg prazosin/kg or 3 mg tolazoline/kg. The results suggested that the mydriatic effect of detomidine was mediated by the alpha 2-adrenoceptors, and that mydriasis was a good model for studying alpha 2-adrenoceptor agonists and antagonists. Although the results suggested that the bradycardia effect of detomidine was partially mediated by alpha 2-adrenoceptors, other unknown mechanisms might also be involved. PMID- 2888445 TI - Neuroleptic malignant syndrome. PMID- 2888444 TI - Comparative renal effects of calcium channel blockers in conscious spontaneously hypertensive rats. AB - Five calcium channel blockers with diverse chemical structures were studied for potential renal selectivity after oral administration of a single dose to conscious spontaneously hypertensive rats. Nitrendipine (3 and 10 mg/kg) and diltiazem (30 and 100 mg/kg) caused significant increases in sodium and water excretion. In comparison, prenylamine (100 and 300 mg/kg) and flunarizine (100 and 300 mg/kg) failed to augment sodium and water excretion. Verapamil caused significant natriuresis only at 30 mg/kg. These data suggest that the diuretic and natriuretic action is not a common property of all calcium channel blockers. Pretreatment with SCH 23390 (20 mg/kg), a dopamine DA1 antagonist, selectively attenuated the diuresis and natriuresis induced by high doses of diltiazem (100 mg/kg) and nitrendipine (10 mg/kg) without blocking the renal responses to hydrochlorothiazide (1 mg/kg). Similarly, reserpinization abolished the renal but not the hypotensive action of diltiazem. Pretreatment with indomethacin (10 mg/kg), a cyclooxygenase inhibitor also significantly attenuated the diuresis and natriuresis elicited by diltiazem (100 mg/kg). These data suggest that intact dopamine and prostaglandin systems in the kidney are required for optimal expression of the renal effects of diltiazem and nitrendipine. PMID- 2888446 TI - Technique of preparation of hemopoietic cells of human fetal liver for transplantation. AB - The preparation of single cell suspension from human fetal liver is described. The technique is based on pressing the liver through wire mesh followed by repeated aspiration into a syringe through needles of decreasing internal diameter. Subsequently, the cell suspension is depleted of cell debris by a "triple medium sedimentation procedure" without net loss of hemopoietic cells. Following centrifugation and resuspension the preparation is ready for either transplantation or storage. About 2 and 11 X 10(9) cells were obtained per liver depending on the age of fetus in the range of 16 and 24 weeks of gestation in three representative preparations. The cell suspension contained comparable numbers of hemopoietic progenitors to the adult bone marrow suspension as assayed using plasma clot diffusion chamber technique. PMID- 2888447 TI - Unusual arteritis causing myocardial infarction in a child. AB - A 5-year-old girl presented with a diffuse inflammatory disease that consisted of fever, lymphadenopathy, splenomegaly, and anterior uveitis. A chest x-ray film indicated an apparently nodular infiltrate. Her condition deteriorated abruptly, and she died of acute myocardial infarction. Autopsy revealed an extensive vasculitis that involved the aorta, pulmonary arteries, and coronary vessels. An aneurysm of the left coronary artery was noted. We present and discuss this case as an unusual arteritis in childhood, closely resembling Takayasu's disease. The presence of extensive erythrophagocytosis in sinus histiocytes hinted at a viral or immunologic origin for this child's disease. PMID- 2888448 TI - Immunohistochemical detection of proliferating cell nuclear antigen in solid human malignancies. AB - Proliferating cell nuclear antigen (PCNA), also known as cyclin, is a cell cycle related nuclear protein that is maximally elevated in late G1 and S phases of proliferating cells. In this study, PCNA was identified by paraffin-section immunohistochemistry in 42 of 64 solid human malignancies, and in several benign tissues known to contain proliferating cells. The PCNA-positive nuclei were randomly distributed and ranged from less than 1% (in most cases) to more than 20% of the neoplastic cells. In general, PCNA positivity correlated with mitotic activity and tumor grade. Further study is necessary to evaluate PCNA as a marker of cellular proliferation and a potential prognostic marker in human malignancy. PMID- 2888449 TI - Eosinophilic granular cells in a cryptorchid testis. AB - Intratubular cells with numerous refractile eosinophilic cytoplasmic granules were identified in a cryptorchid testis from a 17-year-old boy. The staining properties of the granules and the ultrastructural features were studied. The accumulation of lipid or lysosomal inclusions accounted for the observed cytoplasmic granules. These granular cells were probably altered Sertoli's cells, the exact nature and significance of which need further study. PMID- 2888450 TI - Thyroid toxicity and iodothyronine deiodination. PMID- 2888451 TI - Increased thyroxine clearance in rats treated with high doses of a histamine H2 antagonist, SKF 93479. PMID- 2888452 TI - [Endocrine cells of the APUD system in human respiratory organs]. PMID- 2888453 TI - Mapping X-linked ophthalmic diseases. III. Provisional assignment of the locus for blue cone monochromacy to Xq28. AB - Blue cone monochromacy (BCM) is an infrequent X-linked retinal disorder typified by poor central visual acuity and color discrimination, early onset of nystagmus, variable degrees of myopia and astigmatism, and a nearly normal retinal appearance. The physiologic functions of rods and blue cones are preserved. The regional location of the genetic mutation causing BCM has been unknown. We have applied the modern molecular techniques of analysis of restriction fragment length polymorphisms to three multigenerational kindreds in which BCM is segregating. Significant linkage is established to two DNA markers, DXS15 and DXS52, each of which maps to the vicinity of Xq28. Regional localization of the locus for BCM has the potential to improve carrier detection and to provide antenatal diagnosis in families at risk for the disease. PMID- 2888455 TI - The "erythrocyte receptor" of T-lymphocytes and T11 target structure (T11TS): complementary cell interaction molecules involved in T-cell activation. AB - The CD2 or T11 glycoprotein on T-lymphocytes is the receptor for both sheep and human erythrocytes in the formation of spontaneous ("E"-)rosettes. Recent evidence employing monoclonal anti-T11 antibodies suggested that T11 is also a signal transducing molecule with a function in T-cell activation. The present report summarizes the identification of T11 target structure (T11TS), a natural ligand of T11, and its biochemical and functional characterization. T11TS is defined by a mAb to sheep erythrocytes that completely blocks their binding to CD2. It is a glycoprotein of 42 kDa MW expressed on all types of blood cells and some other tissues. While the anti-T11TS mAb used is specific for sheep cells, an antiserum raised to purified T11TS also blocks human autologous E-rosetting. Evidence is presented that the human lymphocyte function associated antigen (LFA) 3, which had recently been shown to be the likely human ligand of CD2, is the structural and functional human homologue of T11TS. Functional studies on T-cell activation employing sheep erythrocytes as one ligand of CD2 indicate that binding of T11TS to the E-receptor provides one of the signals required for T cell activation through the CD2 molecule. PMID- 2888456 TI - Structure and function of the human interleukin 2 receptor gene. AB - The gene encoding the human Interleukin 2 (IL-2) receptor consists of 8 exons spanning more than 25 kilobases on chromosome 10. Exons 2 and 4 were derived from a gene duplication event and unexpectedly also are homologous to the recognition domain of human complement factor B. Receptor gene transcription is initiated at two principal sites in normal activated T cells. Adult T cell leukemia cells infected with HTLV-I show activity at both of these sites, but also at a third transcription initiation site. Resting T cells do not contain detectable IL-2 receptor mRNA. Within 1 hour after stimulation with phytohemagglutinin (PHA), a large, presumably nuclear precursor RNA species is seen, which then gradually disappears. Mature IL-2 receptor mRNA forms appear within 8 hours after stimulation, reach peak levels between 8 and 24 hours, and then decline. Thus in PHA-activated lymphocytes the rise and fall in IL-2 receptor mRNA levels precede by more than 24 hours the peak and decline of IL-2 receptor protein expression occurring at the cell surface. Nuclease S1-protection assays indicate that IL-2 receptor mRNAs may differ in length due to the use of three different polyadenylylation signals. Further, these assays demonstrate the presence of transcripts that lack a 216-base segment within the protein-coding region and thus do not encode a functional IL-2 receptor. Nuclear transcription assays indicate that the increase in IL-2 receptor mRNA is reflected at the level of transcription. Thus, IL-2 receptor gene regulation controls IL-2 receptor expression at the cell surface and is intimately linked to the control of T-cell proliferation. PMID- 2888454 TI - Increased plasma free cortisol in ocular hypertension and open angle glaucoma. AB - Values of plasma free cortisol (not bound to plasma proteins), total plasma cortisol, and percent free cortisol were determined in normal, ocular hypertensive, and open angle glaucomatous subjects. Median total plasma, plasma free, and percent free cortisol levels were higher in ocular hypertensive and glaucomatous individuals. The most significant differences occurred with percent free cortisol values between normal and glaucomatous subjects. There was a significant positive correlation between percent free cortisol and total cortisol levels in normal subjects only. For subjects with glaucoma and hypertension, the percent free cortisol values were independent of the total cortisol values. Multilinear regression analysis also indicated that besides diagnosis and level of total plasma cortisol, male sex, blood sampling late in the day, and increased diastolic blood pressure were the only variables significantly related to increased values of plasma free cortisol and percent free cortisol. Ocular medication for glaucoma and use of beta-blockers were not found to be significant independent variables in the regression models for either plasma free cortisol or percent free cortisol. These observations further suggest that a disorder of the pituitary adrenal axis and/or a binding of plasma cortisol is associated with ocular hypertension and open angle glaucoma. PMID- 2888458 TI - The control of transcription in Saccharomyces cerevisiae. PMID- 2888459 TI - Mechanisms for the stimulatory and inhibitory effects of carbamoylcholine on canine gastric D-cells. AB - We have previously reported that carbamoylcholine (carbachol), a recognized inhibitor of somatostatin release from D-cells, can act as stimulant following pretreatment of cells with pertussis toxin. In the present studies we have observed that pertussis toxin reverses the inhibitory effects of carbachol on D cell stimulated with either cAMP or 12-O-tetradecanoyl-phorbol 13-acetate. Furthermore, the stimulatory effects of carbachol on D-cells pretreated with pertussis toxin potentiated the actions of pentagastrin without further enhancing the release of 3H-inositol triphosphate from prelabeled cells. These studies suggest that carbachol exerts its inhibitory effects on D-cells via pertussis toxin sensitive guanine nucleotide binding proteins at a point distal to the activation of different signal transduction mechanisms and that the stimulatory effects of carbachol are mediated by mechanisms that are independent of membrane phosphoinositide turnover. PMID- 2888457 TI - Regulation of fatty acid synthesis and malonyl-CoA content in mouse brown adipose tissue in response to cold-exposure, starvation or re-feeding. AB - 1. The effect of nutritional status on fatty acid synthesis in brown adipose tissue was compared with the effect of cold-exposure. Fatty acid synthesis was measured in vivo by 3H2O incorporation into tissue lipids. The activities of acetyl-CoA carboxylase and fatty acid synthetase and the tissue concentrations of malonyl-CoA and citrate were assayed. 2. In brown adipose tissue of control mice, the tissue content of malonyl-CoA was 13 nmol/g wet wt., higher than values reported in other tissues. From the total tissue water content, the minimum possible concentration was estimated to be 30 microM 3. There were parallel changes in fatty acid synthesis, malonyl-CoA content and acetyl-CoA carboxylase activity in response to starvation and re-feeding. 4. There was no correlation between measured rates of fatty acid synthesis and malonyl-CoA content and acetyl CoA carboxylase activity in acute cold-exposure. The results suggest there is simultaneous fatty acid synthesis and oxidation in brown adipose tissue of cold exposed mice. This is probably effected not by decreases in the malonyl-CoA content, but by increases in the concentration of free long-chain fatty acyl-CoA or enhanced peroxisomal oxidation, allowing shorter-chain fatty acids to enter the mitochondria independent of carnitine acyltransferase (overt form) activity. PMID- 2888461 TI - The purification and subunit structure of a membrane-bound ATPase from the Archaebacterium Halobacterium saccharovorum. AB - A membrane-bound ATPase from Halobacterium saccharovorum was solubilized using sodium deoxycholate and Zwittergent 3-10 and purified by hydrophobic and ammonium sulfate-mediated chromatography. The enzyme, which had a molecular mass of 350 kDa, was composed of two major (87 and 60 kDa) and two minor (29 kDa and 20 kDa) subunits. The halobacterial ATPases appear to be unlike any other ATPase described to date. PMID- 2888460 TI - A malonyl-CoA-binding protein from liver. AB - A soluble protein that binds malonyl-CoA without requiring cofactors has been purified from rat liver. Until saturated, it competes with fatty acid synthetase for free malonyl-CoA, temporarily reducing the rate of fatty acid synthesis at low levels of malonyl-CoA, as in fatty acid synthetase--coupled assays for acetyl CoA carboxylase. These assays yield low estimates for carboxylase activity with crude and partially purified homogenates containing the malonyl-CoA-binding protein. The protein does not inhibit assays for carboxylase activity that measure nonvolatile radioactivity incorporated from bicarbonate or NADH oxidation coupled to ADP formation. It has an Mr of 180,000 and a subunit of 90,000. It has a lower affinity for ATP, ADP, and acetyl-CoA and none for CO2 or fatty acid synthetase. No enzymatic function has been identified. The protein may regulate malonyl-CoA-binding enzymes. PMID- 2888462 TI - Increased messenger RNA concentration for carbamoyl-phosphate synthase II in hepatoma 3924A. AB - Previous investigations demonstrated that carbamoyl-phosphate synthase II (synthase II) (EC 6.3.5.5) activity, amount, and in vivo synthetic rate increased approximately 9-fold in the rapidly proliferating rat hepatoma 3924A compared to normal liver. This study provides evidence by Northern and RNA dot blot hybridizations of a 13-fold increase in the amount of hepatoma 3924A synthase II mRNA compared to levels in normal liver. Southern and DNA dot blots indicated amplification of CAD hepatoma 3924A synthase II gene product. PMID- 2888463 TI - Inhibition of neutrophil degranulation and superoxide production by sulfasalazine. Comparison with 5-aminosalicylic acid, sulfapyridine and olsalazine. AB - Sulfasalazine is a potent inhibitor of superoxide production and granule enzyme release by stimulated neutrophils, and modulation of these responses may contribute to its anti-inflammatory properties. It is a composite drug consisting of 5-aminosalicylic acid and sulfapyridine joined through an azo linkage. To investigate which functional groups on the molecule are active against neutrophil responses, 5-aminosalicylic acid, sulfapyridine and olsalazine were added to cells stimulated with fMet-Leu-Phe or immune complexes. The inhibitory effects of sulfasalazine on superoxide production, degranulation and neutrophil-mediated collagen degradation were closely mimicked by olsalazine, with the other two compounds having little effect on either function. Thus the azo link appears to be the important structural feature of sulfasalazine that affects neutrophil responses. This suggests that sulfasalazine could be anti-inflammatory in its own right rather than just acting as a source of 5-aminosalicylic acid. Our findings are also a favourable indication for olsalazine (Dipentum), which is currently under trial as an anti-inflammatory agent. PMID- 2888464 TI - The cell biology of multiple drug resistance. PMID- 2888465 TI - Effects of opioid compounds on desensitization of the nicotinic response of isolated bovine adrenal chromaffin cells. AB - Opioid compounds have been assessed for their ability to modify desensitization of nicotine-induced catecholamine secretion from cultured, bovine, adrenal chromaffin cells. Dynorphin-1-13 and metorphamide produced protection against desensitization of the nicotinic response at concentrations between 1 and 20 microM while etorphine and morphine only produced this effect at 100 microM. The opioid antagonists, naloxone and diprenorphine, at 100 microM mimicked the weak ability of the opioid agonists to protect against nicotinic desensitization. All opioid compounds tested were considerably more potent at inhibiting nicotine induced catecholamine secretion from the cells than at protecting against desensitization of this response. It is concluded that adrenal opioid peptides probably do not act on adrenal opioid binding sites characterised from ligand binding studies to prevent the nicotinic response from desensitizing. They are unlikely, therefore, to be involved in such a mechanism to maintain catecholamine secretion during stress. PMID- 2888466 TI - Inhibitory effects of niacin and its analogues on induction of ornithine decarboxylase activity by diethylnitrosamine in rat liver. AB - Pharmacological doses of niacin and its analogues were given intraperitoneally to rats with and without coadministration of a hepatocarcinogenic dose of diethylnitrosamine (DEN), and their effects on the induction of ornithine decarboxylase (ODC, EC 4.1.1.17) activity in the rat liver were studied. The induction of ODC activity by DEN was inhibited by 74.3, 85.5, 94.6, 97.6, 72.6 and 55.2% by nicotinamide, nicotinic acid, 3-hydroxymethylpyridine, beta picoline, pyridine-3-aldehyde and ethylnicotinate respectively. When given alone, these analogues did not induce ODC activity. All these compounds are known to have a niacin effect. DEN-induced ODC activity was also inhibited by 84.0, 93.3, 52.8 and 75.9% by 6-aminonicotinamide, picolinic acid, pyridine-3-sulfonic acid and thionicotinamide, respectively, but, peculiarly, they induced ODC activity by their administration alone. These niacin analogues are known to have anti-niacin effects. Tryptophan, N'-methylnicotinamide and isonicotinic acid hydrazide did not affect the DEN-induced ODC activity but could induce ODC by themselves. Tryptophan belongs to the former group and isonicotinic acid hydrazide to the latter group. The reason for these discrepancies is discussed. PMID- 2888468 TI - Drinkwatchers--description of subjects and evaluation of laboratory markers of heavy drinking. AB - Clinical examination and measurement of MCV and GGT were carried out on 124 self referred 'healthy' Drinkwatchers, all of whom had consumed at least 80 g alcohol/day for more than 2 years. The majority (66.1%) were in social classes II and III. Sixty-three subjects (54.1%) had a raised MCV, GGT or hepatomegaly. A raised MCV was significantly more likely to occur in men. Forty-five subjects (36.3%) had an enlarged liver of whom 17 had a normal MCV and GGT. This study shows that MCV and GGT are poor screening tests for excessive alcohol consumption in 'healthy' subjects but, if used at all, MCV appears to be more sensitive in women and GGT in men. Neither test is an adequate substitute for a careful history and full clinical examination. PMID- 2888467 TI - Association of a 9.2-kilobase Pvu II class I major histocompatibility complex restriction fragment length polymorphism with ankylosing spondylitis. AB - We analyzed DNA restriction fragment length polymorphism (RFLP) in 53 white ankylosing spondylitis (AS) patients and 92 healthy controls, utilizing a full length HLA-B7 complementary DNA probe. A 9.2-kilobase (kb) Pvu II fragment was found to be significantly increased in frequency in B27 positive AS patients compared with the B27 positive control group (P = 0.00085, relative risk = 7.2). The presence of both B27 and the 9.2-kb RFLP in an individual conferred a relative risk for AS of 297, compared with a relative risk of 119 in those who had B27 alone. The 9.2-kb RFLP appears to be a marker for AS which, with HLA-B27, contributes further to susceptibility to the disease. Our findings indicate that this fragment and HLA-B27 segregate independently in familial studies of AS. PMID- 2888469 TI - Platelet affinity for serotonin is increased in alcoholics and former alcoholics: a biological marker for dependence? AB - The kinetics of 3H serotonin platelet uptake were studied in alcoholics and former alcoholics to see whether differences found between alcohol-preferring and non-preferring rats could be reproduced in man. Three groups of patients were studied: 10 dependent alcoholics on admission for treatment; 10 dependent alcoholics after 20 days of treatment; 8 former dependent alcoholics, abstinent for 1-11 years. Controls were non-alcoholics, matched for age and sex. The Km for 3H serotonin uptake in platelets was lower in patients from all three groups compared to 15 controls. This phenomenon could be congenital or induced by the previous excessive intake of alcohol. We believe that this increased platelet affinity for serotonin, in the absence of cirrhosis of the liver and/or depression could be a marker for alcohol dependence, enabling the therapeutic effort to be focussed on these patients. PMID- 2888471 TI - Problems encountered with a drug-addicted patient. PMID- 2888470 TI - [Effect of the administration of triiodothyronine on the metabolism of Sertoli cells in rats]. PMID- 2888472 TI - Advice for anaesthetists? PMID- 2888473 TI - Digital subtraction angiography in Takayasu arteritis. AB - The usefulness and limitation of digital subtraction angiography (DSA) in Takayasu arteritis were investigated in 32 patients. Intravenous DSA was particularly useful in the follow-up of patients with an established diagnosis of Takayasu arteritis. Pulmonary arterial involvement could also be demonstrated with intravenous DSA as obstructive arterial changes and lack of accumulation of contrast medium in the pulmonary parenchyma. Detailed information concerning the site and extent of vascular involvement and development of collateral vessels were obtained with intraarterial DSA. Thickening of the thoracic aortic wall, however, could not be recognized with either intravenous or intraarterial DSA. Conventional angiography of the descending thoracic aortal is still required as an initial examination, particularly when there is no aortic arch involvement. However, there is no doubt that DSA has the potential to become the diagnostic procedure of choice in Takayasu arteritis. PMID- 2888474 TI - Vecuronium and atracurium in patients with end-stage renal failure. A comparative study. AB - Twenty patients with end-stage renal failure, undergoing kidney transplantation, were assigned randomly to receive either vecuronium or atracurium under evoked twitch tension control. The cumulative-dose technique was used to obtain 95% twitch depression (vecuronium: initial bolus 15 micrograms kg-1, increments 6 micrograms kg-1; atracurium: initial bolus 100 micrograms kg-1, increments 40 micrograms kg-1). Using ED95 values derived from the log-probit dose-response curves, vecuronium was 4.6 times more potent than atracurium. The durations of action of the initial cumulative-doses (from end of injection of the last increment to 25% recovery) were 11.1 +/- 3.3 min for vecuronium and 16.2 +/- 3.9 min for atracurium (P less than 0.05). In terms of duration of action of the maintenance doses (vecuronium one-quarter of the total incremental dose; atracurium one-third) some cumulation was observed with vecuronium (interaction time X treatment; cumulation ratio 1.46 +/- 0.31 v. 0.98 +/- 0.10 for atracurium, P less than 0.001). After 2 h of surgery, the mean recovery times (25% to 75% twitch height) did not differ (18.5 +/- 2.8 min and 16.7 +/- 4.4 min). It is concluded that vecuronium might be less safe than atracurium in patients with end stage renal failure undergoing prolonged operations. PMID- 2888475 TI - Distribution and kinetics of 14C-vecuronium in rats and mice. AB - The distribution and kinetics of 14C-vecuronium were studied in rats and mice. 14C-Vecuronium accumulated rapidly in the liver. Both unchanged and metabolized vecuronium were excreted with the bile into the intestines and stomach. Reabsorption in the gut was probably responsible for an enterohepatic increase in radioactivity in the liver after one hour. Excretion through the kidneys increased continuously from low values after the initial peak. Binding in compartments with acid mucopolysaccharides such as cartilage, connective tissue etc., was less important. Blood-brain barrier and placenta were permeable only to a small degree. PMID- 2888476 TI - Electrical and mechanical responses after neuromuscular blockade with vecuronium, and subsequent antagonism with neostigmine or edrophonium. AB - Six unpremedicated patients who had given their informed consent were given vecuronium 0.08 mg kg-1 before elective surgery. Recovery from neuromuscular blockade was measured electrically and mechanically. Neuromuscular blockade was antagonized 1 h after the administration of vecuronium with two doses of neostigmine 2.5 mg (three patients) or edrophonium 0.5 mg kg-1 (three patients). Although the onset of initial recovery was similar, subsequent recovery was faster when measured electrically (EMG) than when measured mechanically. Recovery appeared to be faster in younger patients. Reintroduction of neuromuscular blockade occurred after the second dose of neostigmine 2.5 mg, given to antagonize the block. This did not occur after either dose of edrophonium 0.5 mg kg-1. PMID- 2888477 TI - Atracurium, vecuronium and pancuronium in end-stage renal failure. Dose-response properties and interactions with azathioprine. AB - Dose-response relations for atracurium, vecuronium and pancuronium were determined in patients in end-stage renal failure for the initial neuromuscular blockade (using three cumulative doses) and for the maintenance of stable 90% response (during continuous infusion). All measurements were during renal transplant surgery, and the interaction of azathioprine on neuromuscular blockade was estimated. Mean ED95 doses were (microgram kg-1): atracurium 375.6, vecuronium 67.2, pancuronium 86.6; the initial blockade required significantly larger doses than in normal patients (37%, 20% and 45%, respectively, using ED50 values). Mean infusion rates for 90% sustained blockade in renal failure were (microgram kg-1 h-1): atracurium 409.4, vecuronium 78.3, pancuronium 14.2. The atracurium dose was not influenced by renal function, whereas vecuronium and pancuronium requirements were significantly reduced by 23.2% and 61.5%, respectively, compared with normal patients (previous study). Azathioprine was injected at the rate of 1 mg kg-1 min-1 for 3 min at stable 90% neuromuscular blockade with constant-rate infusion of the neuromuscular blocking drug. This produced a relatively small and transient antagonism of blockade--probably of negligible clinical significance. PMID- 2888478 TI - Mechanism of oxygen activation by tyrosine hydroxylase. AB - The mechanism by which the tetrahydropterin-requiring enzyme tyrosine hydroxylase (TH) activates dioxygen for substrate hydroxylation was explored. TH contains one ferrous iron per subunit and catalyzes the conversion of its tetrahydropterin cofactor to a 4a-carbinolamine concomitant with substrate hydroxylation. These results are in accord with shared mechanisms of oxygen activation by TH and the more commonly studied tetrahydropterin-dependent enzyme phenylalanine hydroxylase (PAH) and strongly suggest that a peroxytetrahydropterin is the hydroxylating species generated during TH turnover. In addition, TH can also utilize H2O2 as a cofactor for substrate hydroxylation, a result not previously established for PAH. A detailed mechanism for the reaction is proposed. While the overall pattern of tetrahydropterin-dependent oxygen activation by TH and PAH is similar, the H2O2-dependent hydroxylation performed by TH provides an indication that subtle differences in the Fe ligand field exist between the two enzymes. The mechanistic ramifications of these results are briefly discussed. PMID- 2888479 TI - Molecular cloning and sequence analysis of cDNAs encoding porcine kidney D-amino acid oxidase. AB - Complementary DNAs encoding D-amino acid oxidase (EC 1.4.3.3, DAO), one of the principal and characteristic enzymes of the peroxisomes of porcine kidney, have been isolated from the porcine kidney cDNA library by hybridization with synthetic oligonucleotide probes corresponding to the partial amino acid sequences. Analysis of the nucleotide sequences of two clones revealed a complete 3211-nucleotide sequence with a 5'-terminal untranslated region of 198 nucleotides, 1041 nucleotides of an open reading frame that encoded 347 amino acids, and a 3'-terminal untranslated region of 1972 nucleotides. The deduced amino acid sequence was completely identical with the reported sequence of the mature enzyme [Ronchi, S., Minchiotti, L., Galliano, M., Curti, B., Swenson, R. P., Williams, C. H. J., & Massey, V. (1982) J. Biol. Chem. 257, 8824-8834]. These results indicate that the primary translation product does not contain a signal peptide at its amino-terminal region for its translocation into peroxisomes. RNA blot hybridization analysis suggests that porcine kidney D-amino acid oxidase is encoded by three mRNAs that differ in size: 3.3, 2.7, and 1.5 kilobases. Comparison of the sequences of the two cDNA clones revealed that multiple polyadenylation signal sequences (ATTAAA and AACAAA) are present in the 3' untranslated region, making the different mRNA species. The efficiency of 3' processing of the RNA was quite different between the two signal sequences ATTAAA and AACAAA. Southern blot analysis showed the presence of a unique gene for D amino acid oxidase in the porcine genome. PMID- 2888480 TI - Membrane reconstitution of high-affinity alpha 2 adrenergic agonist binding with guanine nucleotide regulatory proteins. AB - Regulation of adenylate cyclase by alpha 2 adrenergic receptors requires the inhibitory guanine nucleotide binding protein Ni. A role for this protein has also been suggested in the high-affinity binding of agonists to the alpha 2 receptor. We recently reported that alkaline treatment can selectively inactivate alpha 2 agonist binding and Ni in human platelet plasma membranes [Kim, M.H. & Neubig, R.R. (1985) FEBS Lett. 192, 321-325]. Binding of the full alpha 2 agonists epinephrine and 5-bromo-6-[N-(4,5-dihydroimidazol-2-yl)amino]quinoxaline (UK 14,304) to these membranes was determined by competition and direct radioligand binding, respectively. The high-affinity GTP-sensitive binding of the agonists is lost after alkaline treatment. Binding of [3H]UK 14,304 was reconstituted by poly(ethylene glycol)-induced fusion of alkaline-treated platelet membranes with cell membranes containing Ni but no alpha 2 receptor or with lipid vesicles containing purified guanine nucleotide binding proteins (N proteins) from bovine brain. The reconstituted binding was of high affinity (Kd = 0.4 +/- 0.1 nM), accounted for a substantial fraction of the total alpha 2 receptors (Bmax for [3H]UK 14,304 was 78 +/- 23% of the Bmax for [3H]yohimbine), and was abolished in the presence of guanosine 5'-(beta, gamma-imidotriphosphate) (GppNHp). The brain-specific protein No (predominant guanine nucleotide regulatory protein from bovine brain) was also effective in reconstituting high affinity alpha 2 agonist binding. The results presented here show that a guanine nucleotide regulatory protein of the No or Ni type is necessary for high-affinity alpha 2 agonist binding. These methods should also prove useful for future studies of receptor N-protein interactions. PMID- 2888482 TI - Positioning of a spin-labeled substrate analogue into the structure of delta 5-3 ketosteroid isomerase by combined kinetic, magnetic resonance, and X-ray diffraction methods. AB - We have shown by kinetic and magnetic resonance measurements that a spin-labeled substrate analogue, spiro[doxyl-2,3'-5' alpha-androstan]-17'beta-ol, binds at the substrate site of crystalline delta 5-3-ketosteroid isomerase (steroid delta isomerase; EC 5.3.3.1) of Pseudomonas testosteroni. The spin-labeled steroid is a linear competitive inhibitor with a Ki value (25 +/- 5 microM) that is consistent with dissociation constants obtained by direct binding measurements based on changes in the electron paramagnetic resonance spectrum of the nitroxide, longitudinal relaxation rates of water protons, and longitudinal and transverse relaxation rates of carbon-bound protons of the isomerase. These binding studies yield a stoichiometry for the nitroxide of 1 per subunit of the enzyme. Measurements of the longitudinal relaxation rates of water protons indicate that the 3-doxyl portion of the spin-label is highly immobilized yet is exposed to solvent. Paramagnetic effects of the nitroxide on T1 defined distances to several previously assigned [Benisek, W. F., & Ogez, J. R. (1982) Biochemistry 21, 5816 5825] and newly assigned protons of the enzyme. These distances were then used to locate (with an accuracy of +/- 2 A) the nitroxide moiety at a unique position in a partially refined 2.5-A resolution X-ray structure of native isomerase. Three of five additional proton resonance peaks, attributed to ring-shielded methyl groups, could be assigned to specific residues on the basis of distances from the spin-label in the X-ray structure. The remaining portion of the spin-labeled steroid was then docked into the X-ray structure in a hydrophobic cavity of the enzyme. This position of the steroid is consistent with the steroid binding site previously proposed [Westbrook, E. M., Piro, O. E., & Sigler, P. B. (1984) J. Biol. Chem. 259, 9096-9103]. However, the rotational orientation of this steroid about its long axis could not be unambiguously established. If we assume that steroid substrates and the spin-labeled inhibitor bind to the same site, but with reversal of the 3- and 17-positions, then the phenolic hydroxyl of Tyr-55 is optimally positioned to function as the general acid that protonates the 3-keto group of the substrate, facilitated by the negative end of the dipole of a 10 residue alpha-helix, the only helix in the molecule.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2888481 TI - Chloroplast F1 ATPase has more than three nucleotide binding sites, and 2-azido ADP or 2-azido-ATP at both catalytic and noncatalytic sites labels the beta subunit. AB - The photolabeling of chloroplast F1 ATPase, following exposure to Mg2+ and 2 azido-ATP and separation from medium nucleotides, results in derivatization of two separate peptide regions of the beta subunit. Up to 3 mol of the analogue can be incorporated per mole of CF1, with covalent binding of one moiety or two moieties per beta subunit that can be either AMP, ADP, or ATP derivatives. These results, the demonstration of noncovalent tight binding of at least four [3H]adenine nucleotides to the enzyme and the presence of three beta subunits per enzyme, point to six potential adenine nucleotide binding sites per molecule. The tightly bound 2-azido nucleotides on CF1, found after exposure of the heat activated and EDTA-treated enzyme to Mg2+ and 2-azido-ATP, differ in their ease of replacement during subsequent hydrolysis of ATP. Some of the bound nucleotides are not readily replaced during catalytic turnover and covalently label one peptide region of the beta subunit. They are on noncatalytic sites. Other tightly bound nucleotides are readily replaced during catalytic turnover and label another peptide region of the beta subunit. They are at catalytic sites. No alpha subunit labeling is detected upon photolysis of the bound 2-azido nucleotides. However, one or both of the sites could be at an alpha-beta-subunit interface with the 2-azido region close to the beta subunit, or both binding sites may be largely or entirely on the beta subunit. PMID- 2888483 TI - Mitochondrial ATP synthase complex: interaction of its F1 adenosinetriphosphatase moiety with the heavy atom iodine. AB - Studies were carried out to determine whether a simple electron-dense "heavy atom" like iodine could be introduced selectively into one or more of the subunits of the mitochondrial ATP synthase complex of rat liver. Surprisingly, very low amounts of iodine are incorporated into the isolated F1 moiety of this complex under conditions which result in a marked loss of catalytic activity. ATPase activity is inactivated in a concentration-dependent manner at pH 7.5 with half-maximal inactivation occurring at about 40 microM iodine. A maximum of only 10 atoms of iodine are incorporated per F1 molecule under conditions where inhibition of ATPase activity is linearly related to iodine incorporation. The molecular size of F1 after iodination is unchanged, indicating that inactivation is due to modification of essential amino acid residues rather than subunit dissociation. Treatment of F1, with 20-50 microM [125I]iodine followed sequentially by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography showed that the beta subunit is preferentially labeled. Significantly, about two atoms of iodine per beta subunit are incorporated. Some iodine amounting to less than 23% of the total radioactivity placed on the gels is recovered in the alpha and gamma subunits whereas no radioactivity is detected in the delta and epsilon subunits. Iodination of F1 appears to modify essential residues other than those involved in substrate or product binding per se. Thus, nucleotide binding to F1 is unaltered by iodine, and neither phosphate, MgADP, nor MgATP protects F1 against inhibition by this agent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888484 TI - Changes in pyridine nucleotide levels alter oxygen consumption and extra mitochondrial phosphates in isolated mitochondria: a 31P-NMR and NAD(P)H fluorescence study. AB - Isolated rat-liver mitochondria were used to study the relation between mitochondrial NADH levels, oxygen consumption (QO2), and extra-mitochondrial phosphates. Alterations in NADH and QO2 were accomplished by incubating mitochondria with different substrates or varying amounts of exogenous ATPase while monitoring QO2 and NAD(P)H fluorescence. Two sets of conditions were studied: (1) in the presence of excess ADP and inorganic phosphate, an increase in NAD(P)H fluorescence was associated with a linear increase in QO2; (2) when QO2 was driven by the steady-state hydrolysis of ATP by exogenous ATPase, increases in QO2 were associated with proportional decreases in NAD(P)H fluorescence. For all substrates tested this relation was linear; however, the slope was substrate dependent. Different substrates were able to maintain different NAD(P)H levels at the same QO2. To investigate this further, effects of changing substrates at constant QO2 on NAD(P)H and extra-mitochondrial phosphates were determined. Addition of glutamate + malate to mitochondria respiring on citrate caused a 50% increase in NAD(P)H fluorescence, a 41% decrease in ADP, and a 30% decrease in inorganic phosphate. Similar changes for the substrate jump, pyruvate + malate to glutamate + malate were found. Finally, it was determined that a linear relation holds between increases in NAD(P)H fluorescence and increases in QO2 when substrates were varied at constant, physiologic levels of extra-mitochondrial ADP. These results indicate that QO2 depends on NAD(P)H levels as well as on extra-mitochondrial phosphates over a wide range of respiratory rates. PMID- 2888485 TI - Correlation of the turnover number of the ATP synthase in liposomes with the proton flux and the proton potential across the membrane. AB - The fluorescent indicator pyranine was used for recording the internal pH of liposomes. The proton permeability was deduced from the velocity of the internal pH increase which was caused by shifting the external pH from 7 to 9. From valinomycin titration of the proton permeability in the presence of internal and external KCl (0.1 M), the permeability coefficient of H+ (PH) was obtained as 10( 4) cm/s at 22 degrees C. The coefficient was twice this value with the ATP synthase isolated from Wolinella succinogenes present in the liposomal membrane (10 mg protein/g phospholipid). ADP and phosphate had no effect on the latter PH. The protonophore TTFB (5 mumol/g phospholipid) increased the PH by 3 orders of magnitude. The permeability coefficients of H+ and K+ were used for calculating the delta uH and the proton flux associated with the phosphorylation which was driven by gradients of H+ and K+. For the conditions of limiting permeability of K+, the following conclusions were drawn. (1) In the steady state of rapid ion flux, the electrical potential across the liposomal membrane as calculated according to the Goldman equation, is directed opposite to the corresponding Nernst potential which is calculated from the K+ gradient. (2) The maximum turnover numbers of phosphorylation require a delta uH of 200-220 mV across the liposomal membrane. These values of delta uH and the corresponding turnover numbers are close to those brought about by the bacterial electron transport and the coupled phosphorylation. (3) The velocity of phosphorylation is linearly related to the proton flux. The slope of the line can be explained on the basis of an H+/ATP ratio of approx. 3. PMID- 2888487 TI - Transport characteristics of L-glutamate in human jejunal brush-border membrane vesicles. AB - Previous work using human jejunal brush-border membrane vesicles has demonstrated the existence of a distinct transport system in man for acidic amino acids. This system is energized by an inwardly directed Na+ gradient and an outwardly directed K+ gradient. These studies further characterize the transport of L glutamate in the human jejunal brush-border membrane vesicles. Efflux studies were performed by loading the brush-border membrane vesicles with radiolabeled L glutamate and sodium chloride. Extravesicular K+ accelerated the efflux of L glutamate when compared to extravesicular Na+ or choline, indicating that potassium serves to recycle the carrier. Unlabeled extravesicular L-glutamate (but not D-glutamate) also enhanced the efflux of radiolabeled L-glutamate demonstrating that there is a bidirectional similarity to the transport system. The effect of pH on the transport system was also investigated by varying the intravesicular and extravesicular pH from 5.5 to 9. A pH environment of 6.5 produced the highest initial uptake rates as well as the greatest overshoots for transport of L-glutamate into brush-border membrane vesicles. The imposition of an inwardly directed pH gradient (5.5 outside, 7.5 inside) accelerated both the influx and efflux of L-glutamate. These results demonstrate that the L-glutamate carrier system in human jejunum appears to have similar energizing characteristics in either direction across the brush-border membrane. In addition, the system operates at an optimal pH of 6.5 and protonation of the system may enhance its mobility. PMID- 2888486 TI - Fusion of negatively charged liposomes with clathrin-uncoated vesicles. AB - The interaction of lipid vesicles with uncoated vesicles from bovine brain has been studied by fluorescence energy transfer between fluorescent lipid analogs (NBD-PE, Rh-DOPE), by loss of fluorescence self-quenching (NBD-PE, carboxyfluorescein) and by freeze-fracture electron microscopy. The fluorescence techniques monitor the mixing of membranous lipids and the induced release of encapsulated material. The results demonstrate a mixing of the negatively charged lipid (PA, PS) vesicles with the uncoated vesicles. In parallel with the lipid mixing a release of intravesicularly encapsulated material takes place. Lipid vesicles composed of zwitterionic lipids (PC, DOPC, PC:PE) do not specifically interact with uncoated vesicles. The electron micrographs reveal single fusion events. Studies on the kinetics are consistent with a fusional mechanism of the negatively charged lipid vesicles with uncoated vesicles. PMID- 2888488 TI - Regulation of PAF-acether (platelet-activating factor) biosynthesis in cultured human vascular endothelial cells stimulated with thrombin. AB - The regulating mechanisms of PAF-acether (platelet-activating factor) biosynthesis in cultured human vascular endothelial cells stimulated with thrombin were investigated. The formation of PAF-acether was maximal at 5 min after stimulation and gradually decreased for up to 30 min. Thrombin induced a rapid 3-4-fold increase in the activity which was maximal by 1 min after stimulation and returned progressively to basal level within 10 min. The thrombin induced enhancement in acetyltransferase activity was due to an increase of the Vmax of the acetylation reaction without a significant effect on the apparent Km of the enzyme for acetyl-CoA. Human endothelial cells also exhibited a basal PAF acether acetylhydrolase activity which was not altered upon thrombin stimulation. The pretreatment with 2 mM phenylmethylsulfonyl fluoride (PMSF), a serine proteinase inhibitor reported to block the acetylhydrolase, induced about 2-times more PAF-acether production in response to 2.5 U/ml thrombin stimulation. However, this enhancement of PAF-acether formation seems to be not only due to the inhibition of the acetylhydrolase, but also to the influences on the activities of the acetyltransferase and other enzymes such as phospholipase A2. These results suggest a key role for acetyltransferase and acetylhydrolase in the regulation of PAF-acether formation and catabolism in thrombin-stimulated human endothelial cells. PMID- 2888489 TI - Correlation of changes in transglutaminase activity and polyamine content of neoplastic tissue during the metastatic process. AB - Transglutaminase activity and the levels of the polyamines putrescine, spermidine and spermine were measured in two transplantable rat sarcomata: P8 which metastasises consistently to the lung, and P7 which metastasises infrequently. With the P7 sarcoma no metastases were detected following implantation; similarly, no significant changes occurred in the levels of transglutaminase activity, putrescine, spermidine or spermine during tumour growth. However, with the P8 sarcoma at approx. 30 days after implantation there was a marked decrease in transglutaminase activity, mirrored exactly by a 20-fold increase in the levels of acid-soluble putrescine. Measurement of covalently-bound polyamines in the P8 sarcoma indicated a significant and corresponding decrease in the levels of bound putrescine. The timing of these changes coincided with the time at which the P8 sarcoma was shown to have metastasised, and suggests that the changes observed may be related to this phenomenon. PMID- 2888490 TI - Preganglionic stimulation increases the phosphorylation of tyrosine hydroxylase in the superior cervical ganglion by both cAMP-dependent and Ca2+-dependent protein kinases. AB - Electrical stimulation of the preganglionic cervical sympathetic trunk increases the phosphorylation of tyrosine hydroxylase in the superior cervical ganglion of the rat by a nicotinic mechanism and by a noncholinergic mechanism. We have measured the incorporation of [32P]Pi into specific tryptic phosphopeptides in tyrosine hydroxylase in order to identify the protein kinases that phosphorylate this enzyme in electrically stimulated ganglia. 32P-labeled tyrosine hydroxylase was isolated from the ganglion by immunoprecipitation and polyacrylamide gel electrophoresis and was subjected to tryptic hydrolysis. Seven tryptic peptides were resolved from these hydrolysates by two-dimensional thin-layer electrophoresis and chromatography. Preganglionic stimulation (20 Hz, 5 min) increased the incorporation of 32P into four of these peptides. In the presence of cholinergic antagonists, however, electrical stimulation increased the labeling of only one phosphopeptide. From a comparison of the effects of preganglionic stimulation with the effects of agonists that activate specific protein kinases, we conclude that electrical stimulation increases the phosphorylation of tyrosine hydroxylase by both a cAMP-dependent protein kinase and a Ca2+/calmodulin-dependent protein kinase. The nicotinic component of preganglionic stimulation appears to be mediated by a Ca2+/calmodulin-dependent protein kinase, while the noncholinergic component appears to be mediated by cAMP dependent protein kinase. Although protein kinase C can phosphorylate tyrosine hydroxylase, this kinase does not appear to participate in the stimulation induced phosphorylation of tyrosine hydroxylase in the superior cervical ganglion. PMID- 2888491 TI - The effect of dexamethasone, insulin and triiodothyronine on microsomal NADPH cytochrome-c (P-450) reductase in primary cultures of isolated hepatocytes. AB - NADPH-cytochrome-c (P-450) reductase, a flavoprotein, is a constituent of the hepatic microsomal polysubstrate monooxygenase and catalyzes the transfer of electrons from NADPH to cytochrome P-450. The hormonal regulation of NADPH cytochrome-c reductase activity and protein has been examined in insolated hepatocytes cultured as monolayers for 48 h in Waymouth's MB752/1 medium fortified with insulin, dexamethasone and triiodothyronine. No similarity between the response of NADPH-cytochrome-c reductase and of tyrosine aminotransferase and malate dehydrogenase activity to dexamethasone and triiodothyronine treatment could be detected. In the absence of hormones about 65% of the original NADPH cytochrome-c reductase activity and protein estimated by the immunochemical staining technique was retained. Culture of hepatocytes in insulin (10.0 mU/ml) or dexamethasone (100 nM) alone but not triiodothyronine improved the retention of reductase activity and protein. Only when hepatocytes were cultured in insulin, triiodothyronine and dexamethasone could NADPH-cytochrome-c reductase activity and protein be maintained at the original level. Dexamethasone alone was found to enhance consistently retention of reductase protein, but not reductase activity, to approximately the same level as in freshly isolated hepatocytes. The results suggest that microsomal NADPH-cytochrome-c reductase activity and protein can be maintained in isolated hepatocytes at the original level by culturing the cells in dexamethasone, insulin and triiodothyronine. PMID- 2888492 TI - Phospholipidic second messengers and calcium. AB - A number of signal molecules bind to surface receptors of target cells and generate intracellular messengers from inositol-containing phospholipids. The phosphatidyl inositol (4, 5) bisphosphate is hydrolyzed into inositol (1, 4, 5) trisphosphate and diacylglycerol. These messengers, via changes in the concentrations of cytosolic Ca2+ and H+ and/or protein phosphorylations, couple the signal to a variety of responses including activation of metabolism, secretion, aggregation, phototransduction, cell proliferation and possibly contraction. PMID- 2888493 TI - Thy-1: a lymphoid cell subset marker capable of delivering an activation signal to mouse T lymphocytes. AB - Monoclonal anti-Thy-1 antibodies are capable of activating mouse T cells in the absence of an antigen-specific signal. Therefore, Thy-1 appears to be connected to an alternative signal transduction pathway, operative in thymocytes as well as in neuronal cells, since this molecule is also present on brain. Biochemical data have shown that this molecule is differentially glycosylated with respect to its cellular distribution. Structure and sequence comparisons revealed a strong homology with the immunoglobulin primordial domain. In addition, the Thy-1 glycoprotein has the particularity of being anchored to the membrane via a glycophospholipid tail. Gene transfer experiments in different cell types have been performed to analyze the mechanism of the Thy-1 pathway of activation. PMID- 2888494 TI - Reproductive tract lesions in male mice treated neonatally with tamoxifen. AB - Male mice of the NMRI/Tg strain were treated with tamoxifen for the first 3 days after birth. The affected mice were sterile, with multiple reproductive tract lesions. These lesions included testicular hypoplasia, intraabdominal testes, epididymal cysts, and squamous metaplasia of accessory glands. PMID- 2888495 TI - In vivo pharmacological characterization of alpha adrenergic receptors in sheep myometrium and their physiological meaning. AB - Utero-cervical responsiveness to alpha-adrenergic receptor stimulation was electromyographically evaluated in vivo in adult ovariectomized ewes. Spontaneous motility and drug-induced changes were quantified with a microcomputer. Our results suggested that the two activity patterns previously described on the ovine genital tract could be respectively controlled by alpha-2 and alpha-1 adrenergic mechanisms. Alpha-2 receptors could be assigned to a chronotropic function by activating a hypothetical zone triggering the outbreak of discrete episodes of motility (regular activity); this function is apparent at the cervix even in the absence of estrogen priming. On the other hand, alpha-1 receptors could be assigned to an inotropic function, regulating mainly the magnitude of estrogen-dependent utero-cervical motility (irregular activity). PMID- 2888496 TI - Localization of gamma-butyrobetaine hydroxylase in the rat testis. AB - The activity of gamma-butyrobetaine hydroxylase in testes is comparable on a protein basis to the amount of activity found in liver and accounts for a significant amount of the total activity found in the rat. The enzyme is localized to the seminiferous tubules of the testes. In attempting to further localize this enzyme, activity remained the same when reported on a protein basis in cryptorchid testes as compared to controls, and activity was found in bovine sperm cells obtained from the caput epididymis. These results are consistent with the localization of this enzyme in both the Sertoli cells and the germ cells. PMID- 2888497 TI - Up- and down-regulation of membrane receptors as possible mechanisms related to the antiulcer actions of milk in rat gastric mucosa. AB - The effects of a cow's milk diet on receptor activity and histamine metabolism in gastric glands and mucosa isolated from adult rats were examined. The milk diet was associated with (1) a decreased mobilization of H2 receptors by histamine and (2) an increased mobilization of PGE2 (prostaglandin E2) receptors in mucous cells (cytoprotective effect) and parietal cells (antiacid effect). These changes are not observed for the receptors reducing pentagastrin- and histamine-induced gastric acid secretion (pancreatic/enteroglucagons, somatostatin) and stimulating mucus, bicarbonate and pepsin secretions in the rat (secretin). Cimetidine produced a parallel displacement of the histamine dose-response curve, suggesting competitive inhibition between this classical H2 receptor antagonist and histamine in the two experimental groups. Prostaglandins and other components in milk such as EGF (epidermal growth factor) and somatostatin might therefore protect gastric mucosa by a differential control of PGE2 and histamine H2 receptor activity either directly (PGE2 in milk) or indirectly (inhibition of endogenous histamine synthesis/release and stimulation of PGE-I synthesis/release). PMID- 2888498 TI - Gene diagnosis: detection of genetic disorders by DNA analysis. PMID- 2888499 TI - Opioid agonist/antagonists in general anaesthesia. AB - Pain is a symptom that is universally recognized yet poorly treated. Almost every patient undergoing surgery will experience pain postoperatively. There is increased interest in the control of this pain and many new analgesics have been introduced. One such group of analgesics, the agonist/antagonist opioids, has evoked much interest among anaesthetists. PMID- 2888500 TI - Neuroleptic malignant syndrome superimposed on tardive dyskinesia. AB - A 30-year-old man with a 3-year history of tardive dyskinesia developed a neuroleptic malignant syndrome while having reserpine and lithium; his symptoms worsened following three doses of neuroleptic medication and improved with bromocriptine. The pre-existing dyskinesia made the presentation confused, and delayed proper diagnosis. PMID- 2888501 TI - Changes in auditory P3 event-related potential in schizophrenia and depression. AB - Event-related potentials during a two-tone discrimination task were recorded in 24 schizophrenic patients, 16 depressed patients and 59 control subjects. Recordings were made when patients were medication-free. Fourteen schizophrenic and 13 depressed patients were retested at 1 and 4 weeks after the start of treatment, and 13 schizophrenic patients were also tested between 6 and 24 months after the initial recordings. In the schizophrenic group, the P3 latency was significantly prolonged compared with that in the control and the depressed groups, and remained unchanged both after 4 weeks treatment with therapeutic doses of neuroleptic drugs and at long-term follow-up. In the depressed group, the P3 latency did not differ from that of controls. P3 amplitude by contrast was reduced in both the acutely depressed and schizophrenic groups and following treatment became normal in the depressed group but remained reduced in the schizophrenic group. It is suggested that a prolonged P3 latency and reduced P3 amplitude indicate an impairment of auditory information processing in some patients with schizophrenia which is independent of the presence of acute psychotic symptoms and is not influenced by neuroleptic medication. PMID- 2888502 TI - Depression in the elderly living in the community. Its presentation and features. AB - A prevalence of depression of 13% was found among 139 coloured persons aged 65 years and over, living in the community in Cape Town, which accords with figures elsewhere. A high rate of hypochondriasis was found, but there was a low rate of suicidal intent, which could be explained by good social support. Observed depression and a depressed mood occurred in almost all depressed patients; as defined in the Present State Examination, these items appear to be an excellent screen for depression. PMID- 2888503 TI - CSF neuropeptides in euthymic bipolar patients and controls. AB - Levels of vasopressin, somatostatin, neurotensin, vasoactive intestinal peptide, corticotrophin-releasing factor and adrenocorticotrophin in CSF were determined in lithium-treated and unmedicated euthymic bipolar patients and controls, in a search for a trait marker in affective disorder. No group differences in levels of these peptides were found. Highly significant positive correlations were found among these peptides (with the exception of neurotensin), suggesting that their presence in CSF is functionally significant, as opposed to the result of random diffusion from the interstitial space of the brain. PMID- 2888504 TI - The relative stability of positive and negative features in chronic schizophrenia. AB - The mental states of 92 inpatients with chronic schizophrenia were assessed on two occasions 4 years apart. The relationship between the two ratings was examined in the 84 patients who were either consistently on or consistently off neuroleptics. Negative features were more stable than positive, but were not irreversible. Every feature examined was shown to resolve in some cases. PMID- 2888505 TI - Khat psychosis. PMID- 2888506 TI - A patient with resistant schizophrenia. PMID- 2888508 TI - Peripheral gangrene associated with beta-blockade. PMID- 2888507 TI - Ethanol retards desensitisation of simple phobias in non-alcoholics. AB - Twenty non-alcoholic patients with DSM-III defined simple phobias for small animals received behavioural approach tests and exposure therapy while under the influence of a moderately intoxicating dose of ethanol or after placebo administration. Ethanol did not demonstrate any acute anti-anxiety effect, but retarded the rate of behavioural in vivo desensitisation, without changing the final treatment outcome. State-dependent effects of ethanol on anxiety were not demonstrated. This study supports prior research indicating no anti-anxiety or 'tension-reducing' effects of ethanol for simple phobias. PMID- 2888509 TI - Prospective trial of operative versus non-operative treatment of severe vesicoureteric reflux in children: five years' observation. Birmingham Reflux Study Group. AB - Children with severe vesicoureteric reflux were allocated randomly to either operative or non-operative treatment and followed up. Altogether 161 children were observed for two years, of whom 104 were followed up for five years. Reflux was abolished in 98% of ureters reimplanted, but more than half of the patients treated non-operatively continued to show severe reflux at five years. Two patients progressed to end stage renal failure, and a further four with extensive bilateral renal scarring became hypertensive. There were no significant differences between treatment groups in the incidence of breakthrough urinary infection, renal excretory function and concentrating ability, renal growth, progression of existing renal scars, or new scar formation. Progressive scarring occurred at all ages but was significantly more common during the first two years' observation. Furthermore, new scars developed exclusively during the first two years' observation, affecting 10 children aged 2-7 at allocation. Neither treatment can claim superiority or fully protect the kidneys from further damage, and efforts must continue to be directed towards identifying those at risk before scarring develops. PMID- 2888510 TI - Analgesic effect of somatostatin analogue (octreotide) in headache associated with pituitary tumours. PMID- 2888512 TI - Acute stress erosions: can they be prevented? PMID- 2888513 TI - Adult onset Hallervorden-Spatz disease with neurofibrillary pathology. A discrete clinicopathological entity. AB - Three adults with progressive cognitive decline and extrapyramidal dysfunction were studied. They were all mentally retarded women without known chromosomal abnormalities, ranging in age at the time of onset from 31 to 42 yrs with an average duration of illness of 6 yrs. Neurological signs were stereotyped and consisted of a unilateral equinovarus foot posture followed by progressive dementia, rigidity and quadriparesis. Identical pathological findings were noted in all cases. There was marked deposition of iron-containing pigments in the globus pallidus and reticulate zone of the substantia nigra. Numerous axonal spheroids were noted in these areas and in the gracile and cuneate nuclei. In addition to these typical changes of Hallervorden-Spatz disease (HSD), abundant neurofibrillary tangles (NFTs) were found within the hippocampus, neocortex, nuclei of basal forebrain, subthalamic nucleus and brainstem reticular formation. Rare Hirano bodies and granulovacuolar degeneration were noted within the hippocampus; neuritic plaques and amyloid deposits were absent. Ultrastructurally the NFTs were mostly paired helical filaments (PHFs) with a diameter of 20 to 25 nm and a half-periodicity of 80 nm. Straight filaments and incompletely twisted forms were also seen. Immunocytochemistry with polyclonal antibodies to PHFs was positive in a distribution identical to that of Bodian-positive NFTs. Biochemical analysis of frozen frontal cortex from 1 case revealed a 94% depletion of the cholinergic marker enzyme choline acetyltransferase. Somatostatin-like immunoreactivity was within normal range. Study of 1 case with laser microprobe mass analysis revealed evidence of aluminium accumulation in tangle-bearing hippocampal neurons. Adjacent tangle-free neurons failed to show comparable accumulations. These findings indicate that adult onset HSD occurring in mentally retarded individuals may represent a distinct clinicopathological entity associated with neurofibrillary pathology without amyloid deposition. PMID- 2888511 TI - Somatostatin. PMID- 2888514 TI - Stress-induced alterations in neurotensin, somatostatin and corticotropin releasing factor in mesotelencephalic dopamine system regions. AB - The effects of exposure to acute mild footshock stress on concentrations of neurotensin-, somatostatin-, and corticotropin-releasing factor-like immunoreactivity (li) in mesotelencephalic dopamine system regions of the rat were examined. Mild stress exposure resulted in a selective and regionally specific increase in neurotensin-li concentrations in the ventral tegmental area (VTA), source of the dopaminergic innervation of the mesocortical and mesolimbic dopaminergic terminal fields. Concentrations of somatostatin- or corticotropin releasing factor-li were not changed in any area examined. Levels of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid, were increased only in the VTA and medial prefrontal cortex. These data suggest that neurotensin in the VTA may be involved in environmentally elicited activation of certain mesotelencephalic dopamine neurons. PMID- 2888515 TI - Cortical effects of neurotoxic damage to the nucleus basalis in rats: persistent loss of extrinsic cholinergic input and lack of transsynaptic effect upon the number of somatostatin-containing, cholinesterase-positive, and cholinergic cortical neurons. AB - Ibotenic acid injections into the nucleus basalis (Ch4) resulted in a near-total loss of cortical cholinesterase fibers. This loss of cholinergic input is irreversible for at least 6 months. The degeneration of cholinergic input has no transsynaptic effect upon the number of cortical somatostatinergic, cholinergic and cholinesterase-positive (cholinoceptive) neurons. PMID- 2888516 TI - The developmental appearance of Thy-1 antigen in the avian nervous system. AB - A monoclonal antibody against chicken Thy-1 glycoprotein was utilised in an indirect binding assay and an immunohistochemical technique to investigate the developmental appearance of Thy-1 in the chicken nervous system. The largest increase of Thy-1 levels in chicken forebrain during embryonic development coincided with the major period of neuronal development and synapse formation but preceded the major period of myelination. Immunohistochemical localisation studies on sections of chicken cerebellum, retina and spinal cord during this period showed that Thy-1 first appeared in regions of tissue which contained differentiated synapses of axons; however, not all such areas were Thy-1 positive. Areas of tissue rich in actively dividing neuroblasts or postmitotic undifferentiated neurons, such as the external granular layer of the cerebellum, showed very little staining. The disappearance of Thy-1-specific staining with age observed in the white matter of sections of cerebellum and spinal cord was due to the masking effect of myelination and not to a loss of Thy-1 from neuronal membranes. PMID- 2888517 TI - Chronic cocaine administration depletes tyrosine hydroxylase immunoreactivity in the meso-limbic dopamine system in rat brain: quantitative light microscopic studies. AB - Chronic administration of cocaine (10 mg/kg, IP, every 12 hours for 10 consecutive days) produced a large decrease in tyrosine hydroxylase staining axons and terminal boutons in the frontal cortex and nucleus accumbens in rats. This treatment also produced a depletion of tyrosine hydroxylase immunoreactivity in the ventral tegmental area of the midbrain when examined 60 days following the final cocaine injection. These effects were quantitated using a Leitz Data Acquisition and Display System. This analysis revealed a 59% and 65% decrease in tyrosine hydroxylase positive staining terminal processes in the frontal cortex and nucleus accumbens, respectively. Furthermore, quantitative light microscopic analysis showed a 52% decrease in tyrosine hydroxylase positive material in the ventral tegmental area. These data demonstrate that chronic administration of cocaine produces a long-term, if not permanent, loss of tyrosine hydroxylase enzyme in both the cell bodies of the midbrain ventral tegmental area as well as in the nerve terminals in post-synaptic target regions of the forebrain. PMID- 2888518 TI - [Adrenaline activates oxidative phosphorylation of rat liver mitochondria through alpha 1-receptors]. AB - We studied the effects and mode of action of epinephrine on the oxidative phosphorylation of rat liver mitochondria. With either succinate or beta hydroxybutyrate as substrate, i.v. injection of 1.5 microgram/100 g epinephrine increased the respiratory rates by 30-40% in state 3 (with ADP), and by 20-30% in state 4 (after ADP phosphorylation), so that the respiratory control ratio (state 3/state 4) changed little. The respiratory stimulation by epinephrine was maximal 20 minutes after its injection. The action of epinephrine on mitochondria was blocked by pretreatment of the animals with the alpha 1-antagonist prazosin but not by treatment with the beta-antagonist propranolol. I. v. injection of 10 micrograms/100 g phenylephrine evoked the same mitochondrial response as epinephrine. I. v. administration of 50 micrograms/100 g dibutyryl cyclic AMP enhanced glycaemia but did not affect mitochondrial respiration. Epinephrine therefore has an alpha 1-type of action on mitochondrial oxidative phosphorylation. PMID- 2888519 TI - [Importance of urinary enzymes as a marker of post-ischemic proximal tubular involvement in rat]. AB - We have studied in rats the influence of renal ischemia on urinary excretion of three brush border membrane enzymes (gamma glutamyl transferase, alkaline phosphatase and leucine aminopeptidase) and of a lysosomal one (N-acetyl-B-D glucosaminidase). Urines were collected over 24 hours periods during three days before and after a 45 minutes renal artery clamping. Urinary GGT, PAL and LAP excretion were significantly increased on the first day after renal ischemia, but returns to normal values on the second day. Urinary NAG activity increases on the first day, but contrary to the latter enzymes, reached to normal values only on the third day. Enzymuria seems to be a useful marker of tubular injury occurring after a temporary renal ischemia in the rat. PMID- 2888520 TI - [Neurogenic syndrome of inappropriate secretion of antidiuretic hormone]. PMID- 2888521 TI - [Establishment of an animal model for the study of epidemic hemorrhagic fever]. PMID- 2888522 TI - [Complement-mediated solubilization of the immune complex in patients with epidemic hemorrhagic fever]. PMID- 2888523 TI - [Effect of type I allergy on the pathogenesis of epidemic hemorrhagic fever]. PMID- 2888524 TI - [Determination of plasma kallikrein and prekallikrein in patients with epidemic hemorrhagic fever and its clinical significance]. PMID- 2888525 TI - Beta-blocker therapy and the risk of anaphylaxis. PMID- 2888526 TI - Extraadrenal paragangliomas. An immunocytochemical and ultrastructural report. AB - Although the majority of extraadrenal paragangliomas are nonfunctional, some of these tumors are associated with hormone production and clinical symptoms, notably hypertension. The authors have investigated 22 paragangliomas, five of which were diagnosed as clinically functional in a light microscopic immunocytochemical and electron microscopic study (nine cases). Histologically, all the paragangliomas exhibited similar features, with a "Zellballen" pattern of polygonal cells. All 22 cases were strongly immunoreactive to protein gene product 9.5 (PGP 9.5) antisera and moderately reactive to antineuron-specific enolase (NSE) sera. Ten cases (five functional) were focally immunoreactive to antichromogranin sera. Seven cases (four functional) were immunoreactive to neuropeptide Y and enkephalin antisera, and six (five functional) to tyrosine hydroxylase antisera. The clinically functional tumors expressed at least two of the antigens, enkephalin, neuropeptide Y, or tyrosine hydroxylase, whereas none of the 17 nonfunctional possessed more than one of these. Electron microscopic study revealed cells from all the nine cases studied to contain secretory granules. Granule sizes ranged from 100 to 280 nm and the morphologic examination of the secretory granules generally showed a dense core with a membrane-bound halo of variable size. Secretory granules were observed in the five functional cases and these were larger (220-280 nm) than those seen in the nonfunctional tumor cells (100-180 nm). Also, tumor cells from the functional cases contained numerous dilated mitochondrial profiles. PMID- 2888527 TI - Multiple malignant rectal carcinoid tumors with immunocytochemical demonstration of multiple hormonal substances. AB - This case report deals with a patient who presented with 17 small carcinoid tumors of the rectum, the largest measuring less than 1 cm in diameter. After a review of the literature on this subject, this case is believed to be highly unusual in several respects: (1) despite their small size, these tumors resulted in multiple metastases to the regional lymph nodes; (2) both primary tumors and metastases were extensively and strongly argentaffin; and (3) most tumors and metastases contained, when investigated by immunocytochemistry, several biologically active substances such as serotonin, somatostatin, and glucagon-like immunoreactivity. PMID- 2888529 TI - Initiation of carcinogenesis by a dietary deficiency of choline in the absence of added carcinogens. AB - The feeding for 10 or 11 weeks of young male Fischer-344 rats, a diet devoid of choline and low in methionine, leads to the appearance of gamma glutamyltransferase-positive foci of altered hepatocytes in the liver and to the induction of initiated resistant hepatocytes. The latter are known to contain the primary precursor cells for the ultimate development of hepatocellular carcinoma. This initiation of carcinogenesis with the choline-devoid diet is prevented by added choline. These observations indicate that a dietary deficiency may, by itself, without known contaminating or added carcinogens, initiate the carcinogenic process. PMID- 2888528 TI - Liver cell proliferation induced by the mitogen ethylene dibromide, unlike compensatory cell proliferation, does not achieve initiation of rat liver carcinogenesis by diethylnitrosamine. AB - The purpose of this investigation was to determine whether mitogen-induced cell proliferation is as effective as compensatory cell proliferation in achieving initiation of carcinogenesis in rat liver. Male Wistar rats were injected with a single non-necrogenic dose of the hepatocarcinogen diethylnitrosamine (DENA) during the peak of DNA synthesis following the administration of the hepatic mitogen ethylene dibromide (EDB) or a necrogenic dose of CCl4. After subjecting the animals to a promoting procedure, the rats were sacrificed and the initiated hepatocytes were monitored as gamma-glutamyltranspeptidase (gamma-GT) positive foci. The results indicate that while DENA administration during compensatory cell proliferation results in the formation of GT positive foci, no enzyme altered foci were produced when the carcinogen was given during liver hyperplasia induced by EDB, despite the fact that at the time of carcinogen administration, the extent of cell proliferation, as monitored by thymidine incorporation into DNA, was the same in both the groups. PMID- 2888530 TI - Tyrosine aminotransferase gene expression in a temperature-sensitive adult rat liver cell line. AB - Regulation of tyrosine aminotransferase gene expression was studied in an adult rat hepatocyte line (RALA255-10G) which is temperature sensitive for the maintenance of the differentiated liver phenotype. Glucocorticoid hormones such as cortisol were necessary for expression of the aminotransferase gene. In the absence of these steroids, enzyme synthesis, activity, and mRNA accumulation were virtually abolished. In the presence of cortisol at 33 degrees C, RALA255-10G cells showed characteristics of malignant transformation and contained little tyrosine aminotransferase activity, synthesized low levels of this enzyme, and produced low levels of enzyme mRNA. At 40 degrees C, cells maintained in the presence of cortisol regained the normal, differentiated phenotype, and tyrosine aminotransferase synthesis and mRNA accumulation were greatly increased. This increase in aminotransferase synthesis paralleled the increase in the enzyme mRNA. However, after a temperature shift-up, tyrosine aminotransferase activity was increased only for the first 2 days, probably due to thermal inactivation of this enzyme at 40 degrees C. Dibutyryl cAMP alone was not sufficient to induce expression of the tyrosine aminotransferase gene, but it enhanced the induction caused by cortisol. Immunocytochemical studies revealed that the enhanced expression of the tyrosine aminotransferase gene at 40 degrees C and in the presence of cortisol or cortisol plus dibutyryl cAMP resulted from an increase in both the number of cells producing this enzyme and the quantity of tyrosine aminotransferase synthesized per cell. PMID- 2888531 TI - Partial parallelism and partial blockade by bryostatin 1 of effects of phorbol ester tumor promoters on primary mouse epidermal cells. AB - Bryostatin 1, a macrocyclic lactone, functions like the phorbol esters biochemically in binding to and activating protein kinase C. Biologically, however, although it induces some phorbol ester responses such as mitogenesis in Swiss 3T3 cells, it paradoxically blocks the effects of the phorbol esters on differentiation in HL-60 promyelocytic leukemia cells and Friend erythroleukemia cells. Since the phorbol esters induce proliferation and terminal differentiation in distinct subpopulations of epidermal basal cells, we have now examined the action of bryostatin 1 in that system. Bryostatin 1 decreased epidermal growth factor binding and induced ornithine decarboxylase activity, the latter a marker of proliferation. The magnitude of the maximal induction of ornithine decarboxylase was less than for phorbol 12,13-dibutyrate. Bryostatin 1 only transiently caused the morphological change typical of phorbol ester treatment and did not induce transglutaminase or cornified envelope production, markers of the differentiative pathway. Combined treatment with bryostatin 1 and phorbol 12,13-dibutyrate gave similar results to treatment with bryostatin 1 alone, i.e., slight reduction to complete inhibition of phorbol ester action, depending on the response. The mechanism may reflect time dependent block of the protein kinase C pathway by bryostatin 1 in this system; although bryostatin 1 inhibited epidermal growth factor binding at short incubation times (1-2 h), by 4 h of incubation its inhibition was markedly reduced and it correspondingly blocked inhibition of epidermal growth factor binding by phorbol 12,13-dibutyrate. Since induction of terminal differentiation is proposed to be an essential component of phorbol ester mediated tumor promotion in skin, our findings suggest that bryostatin 1 may function as an inhibitor of phorbol ester promotion. PMID- 2888533 TI - Coronary artery to bronchial artery anastomosis in Takayasu's arteritis. AB - A 27-year-old woman presented with ischemia of the left arm and dizziness together with acute lateral wall myocardial ischemia. Physical examination showed narrowing of the arteries to the head and neck and upper limbs suggesting Takayasu's arteritis. Angiography demonstrated pulmonary and systemic involvement. There was complete occlusion of the right upper lobe pulmonary artery and a large collateral artery from the circumflex coronary artery which anastomosed with the right bronchial artery. This anastomotic channel has not to our knowledge been described Takayasu's arteritis. PMID- 2888534 TI - Comparison of the effect of beta adrenergic antagonists with different ancillary properties on isolated canine and human coronary arteries. AB - Experiments were performed on canine and human isolated coronary arteries to characterise human coronary beta adrenoceptors and to determine whether or not beta blocking agents with different ancillary properties unmask the alpha adrenergic effect of noradrenaline in a similar way. The inhibitory effects of atenolol (a beta1 selective antagonist), epanolol (a beta1 selective antagonist with modest intrinsic sympathetic activity), and propranolol (a non-selective antagonist) were assessed on isoproterenol concentration-response curves. Regression analysis provided slopes not significantly different from unity and similar pA2 values for each agent in both preparations. In a second group of experiments, the effects of noradrenaline (10 mumol.litre-1) were assessed in the absence and presence of beta blockade. At equipotent doses (1 log or 2 log units from the pA2 values) each beta blocking agent unmasked the alpha effect of noradrenaline in the same way. This alpha effect of noradrenaline (10 mumol.litre 1) was completely abolished by prazosin 1 mumol.litre-1 in canine coronary arteries but only partially antagonised in human coronary arteries. Thus the property of a beta blocking agent to unmask the alpha adrenergic effect of adrenaline is mainly related to its affinity for the coronary smooth muscle beta adrenoceptors. These beta adrenoceptors were very similar in both preparations and appear to be mainly beta1. The alpha adrenoceptors seem, nevertheless, to be different and resistant to prazosin in human preparations. PMID- 2888532 TI - Pharmacological, molecular, and cytogenetic analysis of "atypical" multidrug resistant human leukemic cells. AB - We previously described the cross-resistance patterns and cellular pharmacology of a human leukemic cell line, CEM/VM-1, selected for resistance to the epipodophyllotoxin teniposide (M. K. Danks et al., Cancer Res., 47: 1297-1301, 1987). Compared to CEM/VLB100, which is a well characterized "classic" multidrug resistant (MDR) cell line, the CEM/VM-1 cells display "atypical" multidrug resistance (at-MDR) in that they are cross-resistant to a wide variety of natural product antitumor drugs, except the Vinca alkaloids, and they are not impaired in their ability to accumulate radiolabeled epipodophyllotoxin. We have extended our characterization of this at-MDR cell line in the present study. In comparison to CEM/VLB100 cells, we found that CEM/VM-1 cells are not cross-resistant to either actinomycin D or colchicine. Verapamil and chloroquine, which enhance the cytotoxicity of vinblastine in CEM/VLB100 cells, had little or no ability to do so in the CEM/VM-1 cells. Membrane vesicles of the two resistant sublines were examined for overexpression of the MDR-associated plasma membrane protein (P glycoprotein, Mr 170,000 protein, or 180,000 glycoprotein) by photoaffinity labeling with the vinblastine analogue N-(p-azido[3-125I]salicyl)-N'-beta aminoethylvindesine. We were unable to visualize the MDR-associated protein in the CEM/VM-1 membranes with this photoaffinity probe under conditions in which the P-glycoprotein was readily seen in the membranes of CEM/VLB100 cells. Furthermore, no hybridization of the pMDR1 complementary DNA was seen in slot blot analyses of the RNA from at-MDR cells, indicating that the mdr gene coding for P-glycoprotein is not overexpressed as is the case in the classic MDR cells. However, cytogenetic analysis indicated that the CEM/VM-1 cells contained an abnormally banded region on chromosome 13q, suggesting that a gene other than mdr may be amplified in these cells. Thus, despite the two cell lines having approximately equal degrees of resistance to epipodophyllotoxins, our data indicate that the mechanism(s) responsible for at-MDR is different from that for classic, P-glycoprotein-associated MDR. PMID- 2888535 TI - [Observation of the serological effect and immune resistance of 2-dose immunization with adsorbed DTP]. PMID- 2888536 TI - [The first isolation of the HFRS virus from the lung of Rattus norvegicus and the blood of patients in JinZhou Prefecture]. PMID- 2888537 TI - Ectopic expression of Thy-1 in the kidneys of transgenic mice induces functional and proliferative abnormalities. AB - Hybrid human--mouse Thy-1.1 genes were injected into pronuclei of Thy-1.2 mice to produce transgenic animals. A hybrid gene composed of the 5' part of the mouse Thy-1.1 gene combined with the 3' human untranslated regions was expressed abnormally in the kidney podocytes, which resulted in severe protein-uria and subsequent death in several founder mice. A hybrid Thy-1 gene composed of the human coding region with the 5' and 3' flanking regions of the mouse gene was expressed abnormally in a different part of the kidney (the tubular epithelia), which resulted in a proliferative kidney disorder. In addition, a neoplasm was found in the brain of one of these mice. These results show that the Thy-1 protein can play an important role in the activation, proliferation, and differentiation of many different cell types. PMID- 2888538 TI - A lymphoproliferative abnormality associated with inappropriate expression of the Thy-1 antigen in transgenic mice. AB - The Thy-1 antigen is a cell-surface glycoprotein of unknown function expressed on mouse T lymphocytes, neurons, and hematopoietic stem cells. To alter the normal pattern of Thy-1 expression during hematopoietic differentiation, we created transgenic mice using a hybrid Thy-1 gene containing a transcriptional enhancer of the mouse immunoglobulin heavy chain gene (E mu). Strains of mice bearing the Thy-1.2/E mu gene express the Thy-1.2 antigen on mature B lymphocytes and their progenitors, and develop a heritable lymphoid hyperplasia characterized by massive expression of the Thy-1.2 antigen in the bone marrow and lymph nodes. The phenotype associated with inappropriate developmental regulation of the Thy-1 gene suggests that the Thy-1 antigen may play a role in inducing activation or differentiation events on early lymphocyte progenitor cells. PMID- 2888539 TI - [Worldwide distribution of mosquitoes in the subfamily Anophelinae and its relation to the transmission of malaria]. PMID- 2888540 TI - [Methods of determining beta blockers in biological material]. PMID- 2888541 TI - Adsorption of catecholamines on a gold electrode surface studied by specular reflection measurement. PMID- 2888542 TI - Adrenergic and serotonergic receptor-blocking potencies of terazosin, a new antihypertensive agent, as assessed by radioligand binding assay. PMID- 2888543 TI - [Calmodulin content in the rabbit reticulocyte and influence of opioid peptides on calmodulin activity in its membrane]. PMID- 2888544 TI - Enhancement of low-dose N-2-fluorenylacetamide-induced hyperplastic liver nodules by pre-existing cirrhosis. AB - The potentiating effect of pre-existing cirrhosis on the formation of hyperplastic liver nodules and/or foci was investigated by feeding a low dose (0.008%) of 2-N-fluorenylacetamide (FAA) in a choline-deficient (CD) diet for 32 weeks to cirrhotic and non-cirrhotic rats. Liver cirrhosis was induced by feeding the rats a CD diet for the preceding 36 weeks. The number and area of gamma glutamyltranspeptidase-positive hyperplastic liver nodules and/or foci were significantly larger in cirrhotic rats exposed to low-dose FAA than in non cirrhotic rats similarly treated. Hyperplastic liver nodules and/or foci were not observed in rats continuously fed a CD diet alone for 68 weeks (control cirrhotic rats). The results suggest that cirrhotic liver might alter the metabolic response to FAA, even at low doses, and lead to enhanced induction of hyperplastic liver nodules and/or foci. PMID- 2888546 TI - Differential diagnosis of genetic disease by DNA restriction fragment length polymorphisms. AB - DNA restriction fragment length polymorphisms (RFLPs) are used for diagnosis of genetic disease in families known to be affected by specific disorders, but RFLPs can be also useful for the differential diagnosis of hereditary disease. An RFLP pattern represents the inheritance of chromosomal markers in a family, and such a pattern may be compatible with the inheritance of a certain disorder in that family. Probabilities to find such a pattern if the disorder were present and if it were absent can be combined with the prior probabilities of disease considered in the differential diagnosis on the basis of previous clinical and laboratory data. Bayes' theorem is used to calculate the posterior probabilities of the diseases in question. This approach is illustrated in a family suffering from either spinal muscular atrophy (an autosomal recessive disease) or Becker muscular dystrophy (an X-chromosomal disorder). Probabilities to exclude a certain disorder can be calculated in advance, as some RFLP patterns are not compatible with the presence of that disorder. PMID- 2888545 TI - A method to quantitate the relative initiating and promoting potencies of hepatocarcinogenic agents in their dose-response relationships to altered hepatic foci. AB - The relative response to various initiating doses of diethylnitrosamine (DEN) and dimethylbenz[a]anthracene of the induction of numbers and size (vol. % of liver) of altered hepatic foci (AHF) in livers of adult female rats of the Sprague Dawley and Fischer 344 (F-344) strains was studied by methods of quantitative stereology in the presence and absence of the promoting agent, phenobarbital (PB, 0.05% in the diet). In all cases, a relatively linear response with dose, even at the lowest doses employed, was obtained except for the numbers of AHF at the highest dose of DEN (30 mg/kg), which was not significantly different from that at a dose of 10 mg/kg in F-344 female rats. Similar dose-response data were obtained at various doses of two promoting agents effective in hepatocarcinogenesis, PB and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in livers of F-344 female rats following initiation with DEN (10 mg/kg) 24 h post 70% hepatectomy. The response to these agents exhibited threshold levels below which no increase in number or vol. % of liver of AHF was noted in comparison with that in livers of animals not treated with the promoting agents. At several subthreshold doses of both PB and TCDD an inhibition of AHF formation and growth (measured as vol. % of liver) was observed. Based on quantitative stereologic calculations, parameters for the estimation for the relative potency of chemicals as initiating or promoting agents have been established. These are defined as: initiation index = no. of foci induced X liver-1 X [mmol/kg body wt]-1 and promotion index = Vf/Vc X mmol-1 X weeks-1, where Vf is the total volume fraction (%) occupied by AHF in the livers of rats treated with the test agent and Vc is the total volume of AHF in control animals which have only been initiated. These parameters were calculated for a number of agents based on data published in the literature and from those reported herein. Neither parameter varied significantly with the dose of the initiating agent based on the data in this paper. The range of promotion indices extended over more than eight orders of magnitude, whereas that of initiation indices was much less variable. Such parameters may be useful as quantitative estimates of the potency of hepatocarcinogenic agents, such values having potential application to risk estimations. PMID- 2888547 TI - Effects of somatostatin analogue SMS 201-995 in non-insulin-dependent diabetes. AB - The 24-h hormonal and metabolic profiles obtained in five non-insulin-dependent diabetics receiving twice daily s.c. injections of the long-acting somatostatin analogue SMS 201-995 (50 micrograms) have been compared with those obtained following placebo injection. Injections were given 30 min before breakfast and the evening meal. GH secretion was not suppressed by the analogue administered in this manner. Despite suppression of serum insulin levels following breakfast and the evening meal, blood glucose levels were similar during the two study periods with no evidence of worsening in diabetic control. Prolonged suppression of plasma glucagon levels was observed and the nocturnal elevation in serum TSH levels was abolished. Free T4 levels fell significantly following the analogue but total T3 levels were unaffected. Blood alanine levels were elevated throughout the study period following SMS 201-995 but changes in lactate, pyruvate, glycerol and 3-hydroxybutyrate were minor. All five subjects suffered gastrointestinal side-effects. SMS 201-995 (50 micrograms) given twice daily before meals does not cause a deterioration in metabolic control, does not suppress 24-h GH secretion and causes significant side-effects in patients with non-insulin-dependent diabetes mellitus. PMID- 2888548 TI - Cellular and humoral immunity in patients with hyperthyroid Graves' disease before, during and after antithyroid drug treatment. AB - Many reports of thyroid stimulating immunoglobulins (TSI) in relation to treatment of Graves' disease have been published and with variable results concerning prediction of permanent remission or relapse after therapy. A range of methods has been used and little has been published measuring TSI by using their ability to stimulate cyclic AMP production in human thyroid cells in monolayer culture. We therefore conducted a prospective study of the predictive value of such an assay in patients with hyperthyroid Graves' disease before, during and after treatment of one year with methimazole and thyroid hormone substitution. Furthermore, the possible relationship between activated suppressor T lymphocytes and TSI in patients followed before, during and after medical therapy has been studied. Patients were divided into two groups; group I, 15 patients, who stayed in remission and group II, 14, who relapsed during the first year after discontinuation of therapy. Mean TSI activity did not differ between the two groups before and during the first half year of medication. In the second half year of treatment, however, mean TSI activity was significantly lower in group I. TSI activity at the end of treatment appeared to have no value in predicting final outcome. Increased TSI activity in group II during treatment was reflected in an increased pertechnetate thyroidal uptake as compared to that in group I. There was no relationship between changes in TSI activity and T cell subsets (Leu 1, 2a, 3a). We found no difference in T lymphocytes between the two groups at any time during observation. Subsets of T lymphocytes in both patient groups did not differ from normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888549 TI - Effect of SMS 201-995, a long-acting somatostatin analogue, on the secretion and morphology of a pituitary growth hormone cell adenoma. AB - The present study reports the effects of SMS 201-995, a long-acting somatostatin analogue, on blood GH levels, glucose tolerance and tumour morphology in a 36 year-old, previously untreated acromegalic woman. Treatment (50 micrograms s.c., 8-hourly) resulted in marked suppression of GH concentration and an improvement in glucose tolerance. After 10 d of treatment, the tumour was removed by transsphenoidal surgery and studied by histology, immunohistochemistry, transmission electron microscopy and morphometry. Histologically, the tumour was an acidophilic adenoma which contained immunoreactive GH in many adenoma cells. By electron microscopy, the tumour was composed of densely granulated somatotrophs containing numerous large secretory granules and many lysosomes showing crinophagy. No cell necrosis or vascular impairment were evident. Using morphometry, the tumour was compared with 10 densely granulated somatotroph adenomas, removed from acromegalic patients not treated with somatostatin. The nuclear and cytoplasmic areas of the adenoma subjected to SMS 201-995 treatment were smaller, and the lysosomes occupied more of the cytoplasmic volume than those of controls. The nuclear/cytoplasmic ratio, cytoplasmic volume densities of endoplasmic reticulum, Golgi apparatus, mitochondria, secretory granules and secretory granule diameters were within the range of control adenomas. In vitro, treated adenoma cells secreted GH and retained responsiveness to both GRH stimulation and somatostatin suppression. The morphologic findings after SMS 201 995 treatment, are consistent with suppression of GH release. There is no evidence that somatostatin has any direct cytotoxic or vasotoxic effects. It appears that SMS 201-995 represents a potent and promising drug in the medical treatment of acromegaly, however, more work is needed to elucidate the mechanism of somatostatin suppression and to provide evidence for adenoma shrinkage. PMID- 2888550 TI - A comparison between the effects of SMS 201-995, bromocriptine and a combination of both drugs on hormone release by the cultured pituitary tumour cells of acromegalic patients. AB - The in-vivo reaction of the plasma GH concentration to the administration of the somatostatin analogue SMS 201-995, bromocriptine and their combination were compared with the in-vitro effects of both compounds and their combination on GH release and the GH tumour cell content of 9 acromegalic patients. Exposure of cultured GH-secreting pituitary tumour cells for 4-96 h to SMS 201-995 showed a variable, but in all instances during longer incubations statistically significant inhibition of GH release, which paralleled the sensitivity of GH secretion to the drug in vivo. This inhibitory effect on GH release was in two of the eight tumours accompanied by a decrease in the GH tumour cell content after 24-72 h of culture. These changes either reflect an inhibition of GH synthesis and/or an increase in intracellular breakdown (crinophagy) of GH and might be the basis for the tumour shrinkage which has been observed in about half of the acromegalic patients during long-term SMS 201-995 therapy. The inhibitory effects of bromocriptine on GH secretion were antagonized by haloperidol, while the inhibitory effect of SMS 201-995 was not affected by the dopamine receptor antagonist. This suggests that the effects of SMS 201-995 and bromocriptine are mediated via separate mechanisms involving different receptors. Additive but no potentiating inhibitory effects of both drugs on GH release were observed in a group of six patients in vivo and in three of six tumours in vitro. PMID- 2888551 TI - The relationships between serum T3 index, thyroid volume, and thyroid stimulating, TSH receptor binding and thyroid growth stimulating antibodies in untreated Graves' disease. AB - This study represents an international double-blind collaborative study of abnormal immunoglobulin activity in untreated Graves' disease. Laboratories in two countries participated in a comparison of thyrotrophin binding inhibiting (TBII), thyroid stimulating (TSAb), and growth stimulating (TGI) immunoglobulins with clinical data, including ultrasonically measured thyroid size. The correlation between TGI and thyroid volume (n = 25, Rs = 0.54, P less than 0.05) and the fact that 9 of 10 patients with high range TGI values had large goitres establish the relationship between TGI and goitre, confirming that the in-vitro activity of these antibodies is related to an in-vivo action. In addition, both TBII and TSAb correlated with serum free T3 indices (TBII: n = 60, Rs = 0.46, P less than 0.001, and TSAb: n = 60, Rs = 0.64, P less than 0.001). Moreover, both TBII and TSAb correlated with thyroid volume (TBII: n = 60, Rs = 0.37, P less than 0.01, and TSAb: n = 60, Rs = 0.41, P less than 0.01) suggesting that these antibodies are also important in development of goitre in Graves' disease. Finally, some correlation between the antibodies was observed. TBII correlated with TSAb (n = 60, Rs = 0.47, P less than 0.001), and in the 16 patients with positive TGI results, this activity correlated with TBII (Rs = 0.54, P less than 0.05), but not with TSAb. Also some cases were found with corresponding high range TBII and TGI, while negative for TSAb, suggesting a close relationship between the in-vitro measurement of TSH binding and TGI. PMID- 2888552 TI - Inverted tandem duplication generates a duplication deficiency of chromosome 8p. AB - An adult female with sever mental retardation and dysmorphic features is described. A de novo chromosomal aberration involving 8p was found. The karyotype was 46, XX, inv dup (8) (p12----p23.1). Dosage studies with the DNA probe D8S7, which is located at 8p23----8pter, showed that the patient was monosomic for this marker. Thus the de novo rearrangement generated a duplication-deficiency chromosome. The possible mechanisms of formation of this abnormal chromosome are discussed. PMID- 2888553 TI - Suggestion of linkage of a major locus for nonsyndromic orofacial cleft with F13A and tentative assignment to chromosome 6. AB - A Danish material of 58 pedigrees with nonsyndromic orofacial cleft, selected out of a comprehensive Danish material for suggestiveness of autosomal dominant inheritance, was studied for linkage with 42 non-DNA polymorphic marker systems. Both cleft lip with or without cleft palate (CL(P)) and cleft lip alone (CP) were, for the purpose of linkage analysis, scored as if they were due to an autosomal dominant gene with complete penetrance. The highest lod score was with the blood clotting factor XIIIA (F13A): for males alone z = 3.40 at theta = 0.00, for females alone z = 0.30 at theta = 0.21, and for these together z = 3.66 at at theta = 0.00 for males and 0.26 for females. Since F13A is known to be located distally on chromosome 6, we tentatively assign a major locus for orofacial cleft to this region. Since both CL(P) and CP pedigrees contribute to the positive score, the question arises whether this locus carries two cleft alleles. PMID- 2888554 TI - The somatostatin analogue SMS 201-995 in acromegaly: prolonged, preferential suppression of growth hormone but not pancreatic hormones. AB - The treatment of acromegaly is not optimal at present, since many patients have continued growth hormone hypersecretion. We report the acute effects of a cyclic octapeptide analogue of somatostatin, SMS 201-995 (Sandoz) in 9 nondiabetic, acromegalic patients between the ages of 30 and 74. We report potent and prolonged dose-dependent effects to suppress growth hormone secretion. A single 50 micrograms dose of SMS 201-995 inhibited growth hormone concentration rapidly within 15 minutes, with maximal effect in 75 minutes. Maximal inhibition was of the order of 80%, with absolute concentrations under 2 micrograms/L for about 6 hours in 5 of 7 patients. Growth hormone concentrations remained significantly suppressed below placebo control for up to 24 hours after a single dose of SMS 201-995, but the inhibitory effects on insulin and C-peptide concentrations were limited to 2 hours. The effects on glucagon secretion were minimal, and also evident for only 2 hours. Mild transient postprandial elevations of plasma glucose and FFA were documented. No adverse effects were noted; routine hematology, biochemistry, and vital signs were not altered. Thus SMS 201-995, with preferential effects at the pituitary somatotroph, holds considerable promise as an attractive and viable alternative for treatment of acromegaly. PMID- 2888555 TI - The decrease in non-specific suppressor T lymphocytes in female hyperthyroid Graves' disease is secondary to the hyperthyroidism. AB - There has recently been considerable interest generated in the significance of changes in the peripheral blood T lymphocyte subsets in patients with autoimmune thyroid disease. Previously, monoclonal antibodies that recognized T cells (Leu 1+ cells), T helper/inducer cells (Leu 3a+ cells), and T suppressor/cytotoxic cells (Leu 2a+ cells), have been used to enumerate these subsets. Using 2 new monoclonal antibodies (anti-Leu-8 and anti-Leu-15), in addition to the above 3 antibodies, and 2-colour flow cytometry, we have enumerated the total T, T helper/inducer, T suppressor/cytotoxic, T helper (Leu 3a+8-), T inducer (Leu 3a+8+), T suppressor (Leu 2a+15+), and T cytotoxic (Leu 2a+15-) cells in 22 patients with hyperthyroid Graves' disease, 38 patients with 131I-treated Graves' disease and 10 patients with Hashimoto's thyroiditis. All patients and controls were female. We found that hyperthyroid patients with Graves' disease had significantly lower T suppressor/cytotoxic cells (p less than 0.05) than did controls, and that this was mainly due to a decrease in T suppressor cells (p less than 0.01). Furthermore, patients with severe hyperthyroidism had a more significant decrease in T suppressor/cytotoxic (p less than 0.001) and T suppressor (p less than 0.001) cells, and an increase in the T helper/inducer:T suppressor/cytotoxic (p less than 0.01) and T helper:T suppressor (p less than 0.01) cell ratios. Patients who were euthyroid more than 1 year after 131I therapy for Graves' disease had normal T cell subsets and ratios, whether or not TSH receptor antibody or other thyroid auto-antibody titres were elevated. Ten females with Hashimoto's thyroiditis also had normal T cell subsets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888556 TI - Systemic analgesics during labor. PMID- 2888557 TI - Epidural and spinal narcotic analgesia. PMID- 2888558 TI - Anesthesia for preterm delivery, breech presentation, and multiple gestation. PMID- 2888559 TI - HCG stimulation in children with cryptorchidism. AB - Fifty-eight children with cryptorchidism have been given hCG stimulation testing, 31 with bilateral cryptorchidism, 22 with unilateral, and 5 with prior unsuccessful orchiopexy. Hormonal studies were carried out prior to and following stimulation. In bilateral cryptorchidism, bilateral descent was observed in 32 percent of cases and in unilateral, the success rate was 55 percent. From their data, the authors concluded that hCG is not indicated if patients present elevated LH and FSH levels or if the basal T levels are in the pubertal range. In the other subjects, the hCG test will permit the determination of the presence or absence of testosterone production and in some cases it results in testicular descent. Finally, in cases of failure that require surgery, the hCG will stimulate tissue growth enhancing the success of orchiopexy. PMID- 2888560 TI - Commentary on HCG stimulation in children with cryptorchidism. PMID- 2888561 TI - Effect of indomethacin on bombesin-like immunoreactivity, somatostatin and gastrin secretion from rat stomach. AB - In the present study the effect of indomethacin-induced prostaglandin deficiency was examined on the release of bombesin-like immunoreactivity (BLI), a putative peptidergic neurotransmitter, from the isolated perfused rat stomach. In addition, gastrin and somatostatin (SLI) secretion was determined. Pretreatment of rats with indomethacin (2 mg/kg X h) resulted in a 3-fold increase of basal BLI secretion. In response to acetylcholine (2 X 10(-6) M) BLI rose from 2,000 to 4,000 pg/min, whereas in controls BLI increased from 400 to 1,400 pg/min. While absolute values for BLI secretion were higher in indomethacin-treated stomachs the relative increase above baseline was lower (100 vs. 250%). In control rats the increase in BLI secretion in response to acetylcholine was abolished when the acidity in the gastric lumen was increased from pH 7 to pH 2. After indomethacin, however, the stimulatory effect of acetylcholine during luminal pH 7 and pH 2 was identical. The decrease of SLI by acetylcholine at luminal pH 7 was abolished in indomethacin-treated stomachs in response to 10(-6) M acetylcholine, and 2 X 10( 6) M had even a stimulatory effect on SLI secretion. Indomethacin pretreatment reduced gastrin secretion at luminal pH 7. These data demonstrate that endogenous prostaglandins exert an inhibitory tone on basal and stimulated BLI and stimulated SLI secretion in the rat stomach. It is suggested that endogenous prostaglandins also inhibit the release of a peptidergic neurotransmitter, similar to their effect on the classical neurotransmitters acetylcholine and norepinephrine. PMID- 2888563 TI - Oxygen consumption and luminescence of Maurolicus photophores stimulated by adrenalin. AB - 1. Abdominal photophores isolated from Maurolicus muelleri freshly collected in the Strait of Messina show a stable oxygen consumption rate of 149.8 +/- 10.1 nmoles g-1 min-1 (N = 31). 2. In the presence of adrenalin (5 X 10(-4) mol/l), the photophores that did not luminesce showed a 78% decrease of the resting oxygen uptake. When the photophores did luminesce, the oxygen consumption never increased above the resting level, instead, it decreased at a different rate according to the amount of light emitted. 3. Photophores pretreated with MnCl2 (40 mM) and stimulated with adrenalin (5 X 10(-4) mol/l), showed a rapid and large emission of light associated with a significant increase of the oxygen consumption above the resting level. 4. The results are discussed with reference to the control mechanism of luminescence in mesopelagic and epipelagic fish. PMID- 2888562 TI - The antihypertensive agents: clinical pharmacology and therapeutic monitoring. AB - There are currently six major classes of antihypertensive drugs. This article focuses on those agents developed and marketed since 1980, paying particular attention to the pharmacokinetics and pharmacodynamics of the various compounds. PMID- 2888564 TI - Pharmacokinetics of kanamycin in the bullfrog, Rana catesbeiana. AB - 1. Kanamycin disposition was studied in bullfrogs (Rana catesbeiana) following single doses IP. Both plasma t1/2 and Vd of the drug increased with increasing time after drug indicating redistribution and tight binding of kanamycin to deep tissue compartments. 2. Kanamycin was eliminated unchanged with a t1/2 plasma = 27 hr; perilymph = 89 hr; endolymph = 183 hr; aqueous humor = 54 hr; and CSF = 58 hr. 3. Kanamycin was absorbed by frogs from environmental water. 4. Environmental conditions must be carefully specified and monitored, as well as the physiological state of the animals when studying the effects of drugs on Amphibia. PMID- 2888565 TI - Effects of biogenic amines and related agonists and antagonists on the isolated heart of the common cuttlefish Sepia officinalis L. AB - 1. Effects of noradrenaline and the related compounds adrenaline, dopamine, octopamine, tyramine, clonidine and isoprenaline were studied in isolated heart preparations from the cuttlefish Sepia officinalis L. 2. All analogues produced a positive inotropic affect, with noradrenaline being the most potent substance. The chronotropic effects of the tested compounds differed widely. 3. The action of substances of the phenylethanolamine group were not antagonized by propranolol but were partly antagonized by phentolamine. 4. Serotonin and its analogues also produced cardio-excitation. These effects were blocked by cyproheptadine but not by methysergide. 5. These results indicate the presence of two different receptors in the Sepia myocardium: one type reacting with noradrenaline most effectively and a second type being stimulated by serotonin. PMID- 2888566 TI - The effects of low pH on egg and alevin survival of kokanee and sockeye salmon, Oncorhynchus nerka. AB - 1. The effects of low pH water on embryogenesis and vitellogenesis in kokanee and sockeye salmon (Oncorhynchus nerka) were investigated. Eggs were exposed to low pH from fertilization to 45 days post-median hatch or to an episodic exposure at pH 4.0. Adult kokanee were also exposed to low pH just prior to ovulation and spawning. 2. The most sensitive stages of development during chronic or episodic exposure to low pH were early embryonic development and newly-hatched alevins. 3. Incubation of eggs at low pH caused a lower median survival, delayed hatching, higher alevin mortality and reduced the efficiency of yolk conversion to tissue of yolk-sac alevins. Those effects were more pronounced when the eggs were fertilized at low pH. 4. Exposure of sexually mature kokanee salmon to acidified water reduced egg and alevin survival, delayed embryo hatching and decreased the percent hatch. Those effects were more pronounced when their eggs were incubated at low pH. PMID- 2888567 TI - Cardiotoxic effects of catecholamines in guinea-pig (Cavia porcellus) and in albino rat (Rattus norvegicus). A comparative study. AB - 1. Cardiotoxic effects of catecholamines in guinea-pigs and rats were compared. Substantially lesser cardiotoxic effects of isoprenaline (2 X 40 mg/kg b.w.) were found in guinea-pigs, as judged by morphologic examination. 2. When isolated hearts were perfused in vitro, noradrenaline (5 X 10(-6) M) induced less damage, judged by enzyme leakage (ASAT) and electron microscopy analysis. 3. Myocardial ATP and creatine phosphate are normally higher in guinea-pigs than in rats, and no difference was found between the two species when subjected to noradrenaline. 4. Glycogen was higher in guinea-pig myocardium, and glycogenolysis during noradrenaline perfusion was substantially greater in guinea-pig hearts than in rat hearts. 5. Obtained data are interpreted with respect to the recent findings that, not only natural history, but also some physiological traits [blood gas transporting system (Kreuzer and Turek, 1981, Medizinische Aspekte der Hohe, pp. 15-23)] make guinea-pigs similar to high altitude mammals, and to earlier findings that high altitude hypoxia adapted rats display lesser vulnerability of cardiac muscle by anoxia and by catecholamines. PMID- 2888568 TI - Metabolism and DNA-binding in vivo of aflatoxin B1 in medaka (Oryzias latipes). AB - 1. The medaka (Oryzias latipes), a small aquarium fish, was shown to possess the capacity to rapidly activate AFB1 in vivo at 25 degrees C to intermediates that bind to DNA. 2. The dose-response for in vivo AFB1-DNA binding was linear over the range 70-550 micrograms AFB1/kg body weight. 3. Maximum binding occurred within the first 24 hr after i.p. injection of [3H]AFB1, followed by a rapid loss of adducts. 4. Aflatoxicol (AFL) and unreacted AFB1 were found by HPLC analysis to be the major products excreted into water after AFB1 exposure, with excretion of AFL as early as 2 min after AFB1 injection. 5. These studies show that medaka possess enzymatic systems similar to rainbow trout (Salmo gairdneri) for biotransformation of AFB1 to the epoxide and to other phase I and phase II metabolites. PMID- 2888569 TI - The venom of the wasp Campsomeris sexmaculata (F.) blocks synaptic transmission in insect CNS. AB - 1. The action of the venom of the wasp Campsomeris sexmaculata on the insect CNS has been studied using the cercal nerve-giant interneuron preparation of the sixth abdominal ganglion of the cockroach. 2. The venom blocks synaptic transmission either transiently (at low concentration) or for a long time (at higher concentration), and causes a permanent depolarization of the neuron with a delay. 3. The venom does not affect directly the axonal excitability. PMID- 2888570 TI - Block of synaptic transmission in insect CNS by toxins from the venom of the wasp Megascolia flavifrons (Fab.). AB - 1. The effects of the venom and its fractions of Megascolia flavifrons have been studied on synaptic transmission and axonal excitability of the giant interneuron of the cockroach. 2. The venom does not affect axonal excitability, but blocks synaptic transmission, and induces postsynaptic depolarization with a delay. 3. Five different active fractions have been recognized. 4. Three fractions of them contain substances already identified as histamine, Thr6 bradykinin and Thr6 bradykinin-Lys-Ala (megascoliakinin). 5. Three fractions contain activities, which have not yet been chemically identified. 6. All of them, and also bradykinin block synaptic transmission; histamine was not active. PMID- 2888571 TI - Some physiological and biochemical indices of zinc toxicity in two freshwater fishes, Clarias lazera and Tilapia zilli. AB - 1. The effects of lethal zinc concentrations on some physiological and biochemical parameters in Clarias lazera and Tilapia zilli were investigated. 2. The analyses of lactate, pyruvate and glycogen in both liver and muscle tissues and the relation among them have been studied in detail. 3. Significant increases were observed in liver and serum proteins, serum alkaline phosphatase (ALP), erythrocyte count (RBCs), haematocrit or packed cell volume (PCV) and haemoglobin (HB) concentrations. 4. Zinc exposure reduced liver and serum acid phosphatase (ACP) as well as liver alkaline phosphatase (ALP). PMID- 2888572 TI - Short-term effects of mercury on survival, behaviour, bioaccumulation and ionic pattern in the catfish (Clarias lazera). AB - 1. The fresh-water fish, Clarias lazera, was exposed to 13 lethal and sublethal concentrations of mercury. 2. The median tolerance limit (TLm) at different exposure periods, 24, 48, 72 and 96 hr, appears to be as follows: 0.96, 0.88, 0.81 and 0.72 ppm Hg2+/l, respectively. 3. From the subacute tests, the maximum acceptable toxicant concentration (MATC) for this fish was between 0.10 and 0.22 ppm Hg2+/l. 4. Behavioural changes, tissue Hg2+ distribution and serum ionic patterns were recorded during both the acute and subacute exposure periods. PMID- 2888573 TI - The toxicity to Clarias lazera of copper and zinc applied jointly. AB - 1. The acute toxicity to juvenile Clarias lazera of a mixture of copper and zinc over a 96 hr exposure period was determined. Fish were exposed to the summation of half the 96 hr TLm value of each toxicant. 2. Percentage survival was much reduced indicating that the metals potentiate each others lethal action. 3. Comparison between metal residues in fish exposed to copper and zinc or to their mixture showed that the uptake of one metal was decreased by the presence of the other. 4. Toxic effects of the mixture on the physiological parameters studied were mainly attributable to copper, indicating that the presence of zinc did not influence the mode of action of copper. PMID- 2888574 TI - Some aspects on L-dopa decarboxylase and p-tyrosine decarboxylase in the central nervous and peripheral tissues of the American cockroach Periplaneta americana. AB - 1. Aromatic amino acid decarboxylase activities toward L-DOPA (L-3,4 dihydroxyphenylalanine), 5-HTP (5-hydroxytryptophan) and p-tyrosine in different tissues of the sclerotized and newly ecdysed cockroach were analyzed. 2. The ratios of enzyme activity with regard to L-DOPA and p-tyrosine varied considerably in the tissues and between the two different growth stages. 3. A DOPA decarboxylase and a p-tyrosine decarboxylase were separated by gel filtration and ion exchange chromatography. 4. The optimal pH requirement for both enzymes was 7.5 with the exception of the one decarboxylating 5-HTP. 5. The molecular weights of the cockroach brain DOPA decarboxylase and tyrosine decarboxylase were estimated to be 120,000 and 100,000, respectively. 6. Unlike the mammalian aromatic amino acid decarboxylase, the cockroach DOPA decarboxylase cannot be activated by a small amount of benzene. 7. An increase of over 50-fold of DOPA decarboxylase activity and a 50% reduction of tyrosine decarboxylase activity in the epidermal tissue of the newly ecdysed animals was observed. 8. In the fully sclerotized cockroach, a reversible endogenous inhibitor(s) of DOPA decarboxylase in the integument was observed, suggesting that the DOPA decarboxylase is suppressed in the epidermal tissues when ecdysis does not occur. PMID- 2888575 TI - The hydra GSH receptor. Pharmacological and radioligand binding studies. AB - 1. The GSH-induced feeding response of hydra has been studied using pharmacological and biochemical methods. 2. Dopaminergic agonists inhibit the response, whereas dopaminergic blocking agents increase it. Phosphodiesterase inhibitors completely inhibit the feeding response. 3. The specific binding of the competitive inhibitor of feeding response, [3H]glutamate, to hydra cellular fractions has been evaluated, and a strong GSH-sensitive binding has been observed in a nematocyst-rich fraction. 4. After pharmacological reduction of the nematocyst number, both feeding response and glutamate binding are severely reduced. 5. Ca2+ ions must be present for the feeding response to occur, whereas glutamate binding occurs both without Ca2+ and in the presence of EDTA. PMID- 2888576 TI - Effect of neurotensin on the smooth muscle of the chicken crop. AB - 1. The effect of neurotensin was studied in the isolated smooth muscle of the chicken crop. 2. This peptide induced concentration-dependent (10(-10)-10(-8) mol/l) contractions of muscle strips. 3. The response to neurotensin was not modified after incubation of the preparation with atropine, indomethacin, naloxone and tetrodotoxin. The neurotensin-exerted contractions are therefore probably myogenic. 4. These properties of neurotensin indicate a possible role for this peptide in the control of crop motility. PMID- 2888578 TI - The identification of arsenobetaine as the sole water-soluble arsenic constituent of the tail muscle of the western king prawn Penaeus latisulcatus. AB - 1. Samples of tail muscle of the western king prawn, Penaeus latisulcatus collected from two locations were examined separately for the presence of arsenobetaine and other arsenic compounds. 2. For both samples the aqueous extract accounted for greater than 97% of the total arsenic. 3. The water-soluble arsenic was present as one compound only which was isolated and identified as arsenobetaine. PMID- 2888577 TI - Melanin storing cells in anuran gut. AB - 1. The location, distribution and morphological characteristics of the pigment cells found in the frog gut are described. 2. The pigment cells show long and large protoplasmic projections. At the ultrastructural level, the nucleus is elongated with prominent nucleolus and dense marginal chromatin. The cytoplasm is full with pigment granules (2500-7500 A) and typical premelanosome structures have been observed. 3. The pigment cells number is higher in the esophagus and large intestine than in the stomach or small intestine and the pigment cells are always located in close contact with blood vessels and nervous structures (ganglia and fibres). 4. We have observed that the pigment content depends upon seasonal variations, increasing during the cold months. 5. We have demonstrated by histological methods that the cells pigment content is melanin. 6. According to their morphological and tinctorial characteristics the anuran gut melanin storing cells are similar to the skin epidermal melanocytes. PMID- 2888579 TI - Effects on dogfish haematology and liver composition after acute copper exposure. AB - 1. Dogfish Scyliorhinus canicula was subjected to experimental acute copper pollution. At the lowest concentration no changes were recorded on haemoglobin levels whilst decreases of the erythrocyte number and haematocrit was found. 2. At higher concentrations near to the lethal doses, a general reduction of all blood parameters was observed. 3. Liver composition (protein, glycogen and lipid levels) was not affected by any copper concentration, over the duration of the experiments. 4. Results are discussed in relation to physiological responses of fish, acute concentration and metal action. PMID- 2888580 TI - Uptake, distribution, and elimination of dietary quinoline by rainbow trout (Salmo gairdneri). AB - 1. Rainbow trout (Salmo gairdneri) readily absorbed 14C-quinoline from pelleted food and whole-body concentrations reached apparent equilibrium after 10 days feeding. Maximum whole body concentrations of 14C-quinoline were only 30 eta g/g of quinoline plus metabolites after 7 days depuration. 2. Initial rates of uptake and elimination varied widely among tissues. The uptake rate constants ranged from 0.0006/day for muscle to 0.1455/day for gallbladder plus bile. Mean elimination half-life for quinoline and its metabolites ranged from 0.4 days in gills to 8.7 days for muscle. 3. Depending on tissue, 58-83% of the stored radioactivity was present as metabolites. About 14% of the radioactivity in the bile was present as glucuronide conjugates. 4. Rainbow trout eliminated 66% of the ingested dose 24 hr after feeding. Biliary and fecal excretion were minor routes of elimination. PMID- 2888581 TI - Activity of the insect growth regulator fenoxycarb (RO-13-5223) on Triatoma infestans (Hemiptera). AB - 1. Fenoxycarb (RO-13-5223) exhibits a strong juvenile hormone type of activity against Triatoma infestans. 2. Topical treatment of last-stadium nymph with the juvenoid caused the formation of superlarvae, adult-larvae intermediates and adultoids. The ED50 was 0.02 microgram/insect. 3. Taking into account abnormalities in oceli, head, thorax, legs, wings, abdomen, conexivo and external genitalia, a scoring system to evaluate the retention of juvenile characters after moulting was developed. 4. Intermediate dose of the juvenoid produced the prolongation of the last instar nymph. 5. Abnormal individuals formed composite cuticles possessing both nymph and adult morphological features. PMID- 2888582 TI - Hepatic metabolism of cyclodiene insecticides by constitutive forms of cytochrome P-450 from lower vertebrates. AB - 1. Multiple forms of cytochrome P-450 were separated from the hepatic microsomes of untreated male rats, pigeons (Columbia livia), razorbills (Alca torda), puffins (Fratercula arctica), and rainbow trout (Salmo gairdnerii), using anion exchange chromatography and DEAE-cellulose. 2. In some cases cytochrome P-450 forms were further purified on hydroxylapatite and carboxymethyl-sephadex columns. 3. Considerable differences in the distribution of forms between these five species were evident from elution profiles on DEAE cellulose, and on analysis of the cytochrome P-450 containing pools by SDS-PAGE. 4. The metabolism of two organochlorine compounds, aldrin and the dieldrin analogue HCE, were studied in (a) intact microsomes and (b) reconstituted systems containing cytochrome P-450, from each of the five species. 5. In spite of their close structural similarity, significant differences were found between the two substrates in the distribution of catalytic activity between the cytochrome P-450 isozymes of each species. PMID- 2888583 TI - Intracellular injection of dopamine enhances acetylcholine responses of neuron R2 in the Aplysia abdominal ganglion. AB - 1. At different levels of the holding potential on neuron R2 membrane in the Aplysia depilans abdominal ganglion, dopamine injected intracellularly increases the amplitude of both inward and outward currents recorded in response to the application of acetylcholine (ACh) to the ganglion surface. 2. The addition of dopamine to the external perfused solution produces generation of inward currents and a decrease in the cell response to the ACh. 3. The enhancing effect of injected dopamine on ACh responses is retained after inhibition of acetylcholinesterase (AChE) by a specific organophosphorous inhibitor, compound Gd-42. 4. The modulating effect of injected dopamine on ACh responses is discussed in terms of the existence of intracellular receptors of neurotransmitters in the differentiated cells. PMID- 2888584 TI - The action of parotoid venom on the heart of the toad (Bufo ictericus ictericus Spix 1824) and its effects on the inhibition caused by vagal stimulation. AB - 1. The administration of crude venom of the parotoid glands of the toad Bufo ictericus ictericus to the in situ (via abdominal vein) or isolated heart of this anuran causes both chronotropic and inotropic effects. 2. While under action of parotoid venom, the heart of the animal is insensitive to vagus nerve stimulation. 3. This blocking of vagal action is dose dependent and it is suggested that it results from a functional antagonism between the venom constituents and the acetylcholine liberated by the nerve endings on stimulation. 4. The venom constituents probably involved in this antagonism are catecholamines (adrenaline and noradrenaline), tryptamine derivatives (serotonin and bufotenidin) and genins (bufagin and bufotoxin), possibly also ATP. 5. Adrenaline, noradrenaline and serotonin, or a mixture of the three, mimic, at least partially, the blocking of vagal action caused by crude venom. 6. The blocking action of crude venom can be prevented by previously or simultaneously adding acetylcholine to the infused crude venom. This prevention is dose dependent. 7. The blocking action persists in the boiled venom and in the material dialysed from crude venom. PMID- 2888585 TI - L-glutamate and potassium-induced contractures in denervated cockroach muscles. AB - 1. The effects of denervation on the mechanical responses to various concentrations of L-glutamate in retractor unguis muscle of cockroach (Perilpaneta americana) was examined, comparing them with contractures induced by high potassium saline. 2. The dose-response curve was shifted to the lower concentrations of L-glutamate after 9 days of denervation. 3. Following a transient increase in the maximum contracture tension, it decreased with days after denervation and reached a constant level by several days. However, from 16 to 20 days after denervation, the tension ratios of the maximum glutamate to potassium contractures were significantly higher than that of the innervated muscles. 4. A sustained contracture was observed on and after treatment of L glutamate in the denervated muscle. Pretreatment of the muscle by concanavalin A facilitated to induce L-glutamate contracture. 5. It was suggested that the sensitivity of the muscle membrane to L-glutamate was increased in the denervated muscle. PMID- 2888586 TI - Changes in the blood of Wistar rats in acute poisoning with ethanol and acetaldehyde. AB - 1. The purpose of the study was to investigate the effect of ethanol and acetaldehyde on the erythrocyte and leucocyte system of Wistar rats. 2. Administration of the ethanol or acetaldehyde caused a considerable drop in the number of erythrocytes, haemoglobin level and haematocrit value in rats. 3. The mean erythrocyte volume was smaller after only 0.5 hr of exposure to ethyl alcohol. 4. The solutions used caused changes in the leucocyte system expressed in distinct neutrophilic leucocytosis. 5. Changes in the leucogram were reflected in the increase in the leucocyte index. 6. The degree of intensity of changes in both the erythrocyte and leucocyte system point to the greater toxicity of ethyl alcohol intoxication than is the case of acetaldehyde in a toxically corresponding dose (i.e. 0.5 and 5 g/kg body wt respectively). PMID- 2888587 TI - Relationships between tissue contaminant concentrations in a small sample of seabirds. AB - 1. The metal and organochlorine contaminant concentrations were measured in a small sample of three seabird species collected from St Kilda, Scotland, UK, and the relationship between concentrations of different contaminants within and between tissues was compared. 2. There was little evidence that the concentration of a contaminant in one tissue was indicative of the concentration in any other tissue. 3. Generally, different contaminants had not co-accumulated in tissues; this was so even for the lipophilic compounds (DDE and PCBs), with the exception of puffin fat. 4. There was a tendency for the species containing the most fat to contain the highest concentrations of lipophilic contaminants and there was some suggestion that the fat in muscle could play a role in determining PCB concentrations. PMID- 2888589 TI - Effects of morphine on adrenaline responses of uteri from progesterone or estradiol treated mice. AB - 1. The effect of a chronic morphine treatment on the in vitro contractile responses of the mouse uterus to adrenaline was studied. 2. Chronic morphine treatment induced a supersensitivity state in the uteri from both progesterone and estradiol treated mice. 3. The acute administration of morphine to the uteri from morphine tolerant-dependent and progesterone treated mice induced a further increase of the contractile effect of adrenaline. 4. Reserpine administration did not further increase the supersensitivity of the mouse uterus to adrenaline induced by a chronic morphine treatment. 5. Reserpine suppressed the acute effects of morphine in the uteri from tolerant-dependent mice. PMID- 2888588 TI - Studies on comparative drug metabolism by hepatic cytochrome P-450-containing microsomal enzymes in quail, ducks, geese, chickens, turkeys and rats. AB - 1. These studies were carried out to compare certain hepatic microsomal drug metabolizing enzymes of quail, ducks, geese, chickens, turkeys and rats. 2. Comparison of relative liver weights of the species indicated that the rats had the largest weight followed by turkeys, ducks, geese, chickens and quail. 3. Rats ranked highest in hepatic cytochrome P-450 content followed in decreasing order by turkeys, geese, chickens, ducks and quail. 4. Microsomal benzphetamine N demethylase activity was significantly higher in geese and turkeys than that for the rest of the species. 5. Geese, chickens and turkeys showed similar aniline hydroxylase activity, while it was markedly lower in quail and ducks with rats being intermediate. PMID- 2888590 TI - Effects of adrenaline on the isolated heart of the trout (Salmo gairdneri R.) before and after transfer from fresh water to sea water. AB - 1. Adrenaline induces positive inotropic and chronotropic effects on the isolated heart of the trout (Salmo gairdnerii) via the stimulation of beta adrenoreceptors. 2. The effects are relatively more marked in winter than in spring. But there is no seasonal variation as in the cel. The intrinsic reactivity of the heart is not basically modified after a transfer from fresh water to sea water. 3. However, after such a transfer, adrenaline induces an increase of the membrane resting potential which suggests that adrenaline can enhance the activity of the Na/K pump and/or modify the Ca/K balance and could improve the cardiac performances during the "crisis period" following the transfer. PMID- 2888592 TI - Comparative acute toxicity of DDT metabolites among American and European species of planarians. AB - 1. DDT metabolism in a North American species of planarian leads to the formation of metabolites more toxic than the parent compound. 2. The increased toxicity of DDT metabolites is similar to acute toxicity data reported previously in a European species. 3. It is suggested that planarians lack a direct mechanism for DDT detoxification, since two North American and one European species are known to metabolize DDT initially to DDE and DDD. PMID- 2888591 TI - Glutathione content and GSH S-transferase activity in midgut gland of Procambarus clarkii. Sex differences, the effect of fasting, and their implications in cadmium toxicity. AB - 1. Glutathione content and GSH S-transferase activity in the midgut gland of Procambarus clarkii (P. c.) of different sex and body weight are presented. 2. Procambarus clarkii females' GSH concentration in the midgut gland decreases to a higher extent upon fasting, compared with males. 3. Procambarus clarkii females, both in control and fasting conditions, have a slightly higher GSH S-transferase activity than males. 4. Cadmium present in water only affects GSH content and GSH S-transferase activity (after 96 hr) in midgut gland, with cadmium chloride concentrations higher than 100 micrograms/l. PMID- 2888593 TI - The distribution of zinc and copper in plasma, erythrocytes and erythrocyte membranes of rainbow trout (Salmo gairdneri). AB - 1. The zinc and copper concentration of plasma was determined in rainbow trout, lake trout, walleye and whitefish. 2. These fish had mean plasma zinc concentrations ranging from 9.3 to 15.1 ppm and copper concentrations from 0.6 to 1.3 ppm. 3. In rainbow trout, the concentration of zinc and copper is greater in the erythrocyte membrane than in the total erythrocyte. 4. Ultrafilterable plasma zinc and copper concentration in rainbow trout was determined to be 0.03 and 0.019 ppm, respectively. 5. Dialysis of rainbow trout plasma against 20 mM EDTA results in removal of 99% of the zinc and 88% of the copper from plasma proteins. PMID- 2888594 TI - Corticotropin-like material in pigeon brains. AB - 1. Pigeon brain acetone powder was extracted with a mixture of acetone, water and hydrochloric acid (40:21:1 v/v/v). The extract was added to a large volume of chilled acetone. 2. The resultant precipitate was washed with cold acetone and then chromatographed on Sephadex G-25. The void volume peak constituted fraction A. The trailing peak immediately following fraction A was divided into two fractions designated B and C. 3. Fraction B (mol. wt less than 5,000) stimulated corticosterone production in isolated rat adrenal cells while the other fractions were devoid of similar ACTH-like bioactivity. 4. None of the fractions showed activity in the opiate radioreceptor assay or hot plate test, implying the absence or presence of only trace amounts of opiate-like materials. Other possibilities that cannot be ruled out include the presence of molecules with substitutions in the sequence by amino acids that result in little or no activity. PMID- 2888596 TI - [Effect of various preventive procedures on the microflora in pathological gingival pockets]. PMID- 2888595 TI - Mechanism of transport and storage of neurotransmitters. AB - This review will focus on the bioenergetics, mechanism, and molecular basis of neurotransmitter transport. As indicated in the next section, these processes play an important role in the overall process of synaptic transmission. During the last few years, direct evidence has been obtained that these processes are coupled chemiosmotically, i.e., the accumulation of neurotransmitters is driven by ion gradients. Two types of neurotransmitter transport systems have been identified: sodium-coupled systems located in the synaptic plasma membrane of nerves (and sometimes in the plasma membrane of glial cells) and proton-coupled systems which are part of the membrane of intracellular storage organelles. From a bioenergetic point of view, the sodium-coupled systems are especially interesting, since it has recently been discovered that many systems require other ions in addition to sodium. It has now been demonstrated in several cases that, besides sodium ions, these additional ions, such as chloride and potassium, serve as additional coupling ions. These systems will be reviewed here in considerable detail with emphasis on the role of the additional ions. In the second part of the review we shall focus on neurotransmitter transport into storage organelles. Although both sodium and proton coupled systems have been reviewed in the past, there has been a shift from a kinetic and thermodynamic to a biochemical approach. In fact, a few transporters have been identified and functionally reconstituted. These developments have of course been incorporated in this review. PMID- 2888598 TI - [Traumatic tooth injuries in children. Examination of patients]. PMID- 2888597 TI - [Traumatic injury to the teeth of children. Classification, etiology and epidemiology]. PMID- 2888600 TI - Lower leg lateral skin flap. Report of 7 cases. PMID- 2888599 TI - Drug-induced left ventricular failure in patients with pulmonary disease. Endomyocardial biopsy demonstration of catecholamine myocarditis. AB - Three patients with severe chronic lung disease had left ventricular failure develop with marked impairment of cardiac function. Ejection fractions by radioactive blood pool ventriculography were 0.17, 0.24, and 0.20. Right ventricular endomyocardial biopsy specimens showed interstitial hemorrhage and foci of interstitial polymorphonuclear leukocytes, strongly suggestive of catecholamine myocarditis. These patients had used beta-adrenergic agonist inhalants and methylxanthines. One of them clearly abused the inhalant and had elevated levels of urinary catecholamines. Progressive deterioration of pulmonary and cardiac function occurred in two patients, with death within three months of the initial myocardial biopsy. Concomitant use of beta-adrenergic agonists and methylxanthines may cause myocarditis with left ventricular failure in susceptible patients. PMID- 2888601 TI - Early diagnosis of hemorrhagic fever with renal syndrome by IgM ELISA technique. PMID- 2888602 TI - [Primary hyperparathyroidism--experiences with concomitant diseases, symptoms, preoperative diagnosis and surgical procedure over a period of 14 years]. AB - In a 14-years period (1970-1984) eight-three patients were operated on for primary hyperparathyroidism (pHPT) at the University Hospital of Erlangen. Special attention was paid to associated diseases, symptoms, preoperative diagnostic parameters were serum calcium, parathyroid hormone in venous blood, cyclic AMP in 24 h-urine. In 15.7% only borderline increased serum calcium values were measured. Ulcer incidence in pHPT was 19% as compared with approx. 7% in the general population. There was no increased incidence of pancreatitis in pHPT. The possibility of an association of pHPT with the Multiple Endocrine Neoplasia (MEN) syndrome was emphasized and measures of early diagnosis proposed. PMID- 2888603 TI - [Effects of electroacupuncture of the hand on the release of transmitters of monoamines in the tissues at different areas of brain in rats]. PMID- 2888604 TI - [Estimating the MAC (maximal allowable concentration) of harmful gases in the submarine chamber]. PMID- 2888605 TI - Regulation of the immune response by ergot alkaloids. AB - We tested the effect of 33 ergot alkaloids (natural and semisynthetic) on the induction of antibody formation in isolated spleen cells by antigen in tissue cultures. The results are quantitatively expressed as the number of antibody forming cells. The group of natural ergot alkaloids (ergopeptines) exerted an effective inhibitory action on the antibody response. Compounds derived from lysergic acid are completely inactive in this respect. A new, very active semisynthetic drug (Table 1, compounds 2) derived from inactive lysergol was described. The compounds interacting with alpha-adrenergic-receptors on lymphocytes (methoxamine, phentolamine, prazosin act synergistically with the inhibitory effect of ergopeptine alkaloids. PMID- 2888606 TI - Systemic Timentin is superior to oral tinidazole for antibiotic prophylaxis in elective colorectal surgery. University of Melbourne Colorectal Group. AB - A prospective, randomized, single-blind, controlled clinical trial was undertaken to compare two different prophylactic antibiotic regimens in patients undergoing elective colorectal surgery. Systemic Timentin, a combination of ticarcillin and the beta-lactamase inhibitor clavulanic acid, was assigned to 101 patients. Oral tinidazole, an agent active only against anaerobic bacteria, was assigned to 102 patients. The wound infection rate was 2.4 percent in the patients receiving Timentin and 14 percent in those receiving tinidazole (P = 0.01). Multivariate analysis of factors affecting the wound infection rate showed that the only factor that independently reached statistical significance was the prophylactic antibiotic used. The mortality of patients receiving Timentin prophylaxis was 3.4 percent compared with 8.9 percent of those receiving tinidazole (P = 0.15). The clinical anastomotic leakage rate was 1.3 percent in patients receiving Timentin and 13 percent in those receiving tinidazole (P = 0.01). These results, together with those of two previously published clinical trials by this group, indicate that antibiotic prophylaxis in elective colorectal surgery should consist of a short course of an agent effective against both aerobic and anaerobic bowel flora. PMID- 2888607 TI - Effect of somatostatin 14 on pure human pancreatic secretion. AB - While it is well known that large doses of somatostatin inhibit human pancreatic enzyme secretion, it is still unknown whether low doses are also effective and whether the peptide is able to inhibit bicarbonate production. Eight subjects with external transduodenal drainage of the main pancreatic duct performed after biliary tract surgery were studied. Somatostatin was infused at progressively increasing rates of 0.05, 0.15, 0.45, and 1.35 micrograms/kg/hr, for 30 min/dose, during pancreatic stimulation with secretin, 25 ng/kg/hr, and cerulein, 10 ng/kg/hr. Somatostatin, at the dose of 0.05 microgram/kg/hr (shown to produce blood levels similar to those measured after a meal) did not affect pancreatic secretion in any of the subjects. The successive three higher doses caused a significant and dose-dependent inhibition of protein concentration and output and of bicarbonate output. Bicarbonate concentration was slightly but significantly reduced only by the two highest doses of somatostatin. At each dose level, the inhibition of protein output was much more marked than the inhibition of bicarbonate output. The maximal inhibition of protein output (at 1.35 micrograms/kg/hr somatostatin) was 73.9 +/- 5.4%, and that of bicarbonate output was 55.9 +/- 6.4%. The results demonstrate that: (1) the administration of somatostatin at a low dose level does not affect human exocrine pancreatic secretion, at least under the experimental conditions of this study; and (2) the administration of larger doses of somatostatin inhibits pancreatic secretion of both protein and bicarbonate dose-dependently. The inhibitory effect on protein output is significantly greater than that on water and bicarbonate production. PMID- 2888608 TI - Effect of somatostatin analog on water and electrolyte transport and transit time in human small bowel. AB - The present study was undertaken to investigate how a somatostatin analog (201 995 Sandoz), which is now commonly used for treatment of patients with gut hormone-producing tumors, affects water and ion absorption and transit time in the normal jejunum. Six healthy volunteers were given somatostatin analog intravenously at a dose of 1 microgram/kg/hr. At the same time, jejunal water and ion movement and transit time were measured using the triple-lumen tube technique [perfusion of a plasma-like electrolyte solution with PEG as a nonabsorbable marker at a rate of 15 ml/min; dye dilution curves ([3H]mannitol, [14C]PEG, BSP) for determination of jejunal transit time]. During somatostatin analog administration, transit time through a 30-cm segment of perfused jejunum increased from 4.0 min to 17.0 min. While the somatostatin analog increased jejunal transit time, it had no effect on net water and electrolyte absorption under steady-state conditions. The effect of somatostatin analog on the proximal small bowel is similar to the action of an eight-times higher dose of intravenous native somatostatin previously studied. The effect of the analog on transit time suggests a potentially beneficial effect in patients with large-volume diarrhea in which no tumor or circulating secretagogue can be identified, such as in pseudopancreatic cholera syndrome. PMID- 2888610 TI - Subtypes of muscarinic receptors in vagal inhibitory pathway to the lower esophageal sphincter of the opossum. AB - We assessed the characteristics of muscarinic neural transmission in the vagal inhibitory pathway to the lower esophageal sphincter (LES) of anesthetized opossums. LES relaxation was induced by electrical stimulation of the cervical vagus. Measurements were made of LES relaxation before and after intravenous administration of nicotinic (hexamethonium), serotonergic (5-Meo-DMT), nonselective muscarinic (atropine), and selective muscarinic (pirenzepine-M1 and 4-DAMP-M2) antagonists. The latency of LES relaxation was increased substantially by pirenzepine and atropine, increased slightly by hexamethonium, but was not affected by 4-DAMP or 5-Meo-DMT. Given as concurrent intravenous infusions, hexamethonium, 5-Meo-DMT and 4-DAMP added to pirenzepine or atropine did not significantly increase LES relaxation latency above that caused by pirenzepine or atropine alone. None of the antagonists alone had a significant effect on percent LES relaxation. The combination of pirenzepine or 4-DAMP with hexamethonium and 5 Meo-DMT did not affect percent LES relaxation. The combination of atropine with hexamethonium and 5-Meo-DMT reduced LES relaxation to 18%. The combination of pirenzepine and 4-DAMP with hexamethonium and 5-Meo-DMT, however, had no effect on percent LES relaxation. We conclude that muscarinic participation in vagally induced LES relaxation exhibits two functional receptor subtypes: (1) M1 receptors that determine LES relaxation latency and are antagonized by pirenzepine or atropine, and (2) non-M1, non-M2 receptors (Mx receptors) that contribute to the magnitude of LES relaxation and are antagonized by atropine, but not by pirenzepine or 4-DAMP. PMID- 2888609 TI - Effect of vasoactive intestinal peptide, somatostatin, neurotensin, cholecystokinin octapeptide, and secretin on intestinal absorption of amino acid in rat. AB - The effects of vasoactive intestinal peptide (VIP), somatostatin (SRIF), neurotensin (NT), cholecystokinin octapeptide (CCK-8), and secretin (SEC) on the intestinal absorption of amino acid were investigated. Six groups of Wistar rats were studied: (1) controls; (2) VIP treated; (3) SRIF treated; (4) NT treated; (5) CCK-8 treated; (6) SEC treated. [3H]Leucine was given intraluminally through a cannula at the ligament of Treitz, a number of blood samples were obtained through a superior mesenteric vein catheter 1-60 min after administration of [3H]leucine, and the radioactivity of plasma was measured to evaluate the absorption of [3H]leucine. It was shown that VIP and SRIF significantly inhibited the absorption of [3H]leucine (by 59.1% and 38.7%, respectively), whereas NT, CCK 8, and SEC significantly enhanced absorption (by 44.2%, 49.6%, and 39.1%, respectively). Radioimmunoassays of VIP, SRIF, and NT showed that at least some of the hormones or peptides exerted their effects on absorption of leucine at or near their physiological concentrations. PMID- 2888612 TI - Influence of drugs on brain neurotransmitters and behavioral states during development. AB - Neurotransmitters are present at very early stages of brain development. They may have trophic effects on maturation of target neurons and mediate the behavioral repertoire of the immature brain. Many centrally acting drugs which are used during pregnancy and early childhood for the treatment of e.g. hypertension, depression, epilepsy, sleep disorders, or hyperkinetism influence brain neurotransmitters and behavioral states. Disturbances observed later in life in animal and man, due to perinatal interference of such drugs with brain neurotransmitters and behavioral states, are not gross physical malformations but rather subtle behavioral and neurological symptoms such as hyperactivity, emotional lability, perceptual motor disturbances, attentional distractibility and sleep disturbances. PMID- 2888611 TI - Study of the pharmacokinetics and pharmacodynamic activity of almitrine bismesylate in infants during the recovery phase following bronchopulmonary dysplasia. AB - The efficacy and pharmacokinetics of almitrine bismesylate were studied in 6 infants (age 2.5-9.5/months) during the recovery phase following bronchopulmonary dysplasia. The infants did not require assisted ventilation, but needed oxygen therapy with an FiO2 of 25-30% in stable condition. One to three hours after a single oral dose of almitrine (1.5 mg/kg), there was a marked increase in transcutaneous PO2 (TcPO2) (mean 2kPa) followed by a regular decrease to the baseline level. Nine to fourteen days after repeated administration of almitrine (1.5 mg/kg/12 h) in 4 children, the mean gain in TcPO2 was only 0.85 kPa. There was a very early flagging in efficacy of almitrine, since none of the children could be weaned from oxygen therapy. The absorption peak occurred 1-3 h after the administration of the compound. The maximum almitrine concentration was 173 +/- 44 ng/ml; plasma clearance was 21.9 +/- 6.6 ml/min and the volume of distribution was 18.7 +/- 2.1 liters/kg. The drug was eliminated biphasically. In the 4 studies with repeated drug administration, the pharmacokinetic results suggested that a steady state was still not achieved after 9-14 days of treatment. These results and the absence of any sustained effect of repeated doses of the drug raise the problem of a particular type of almitrine metabolization in the infant. PMID- 2888613 TI - Renal transport processes and glutathione conjugate-mediated nephrotoxicity. PMID- 2888614 TI - Species differences in disposition of benzo[a]pyrene. AB - Comparison of disposition of benzo[a]pyrene (B[a]P) among Sprague-Dawley rats, Gunn rats, hamsters, and guinea pigs was performed. [3H]B[a]P was administered intratracheally to animals, and the rate of excretion of radioactivity into bile, types of metabolites of B[a]P in bile, and distribution of radioactivity among tissues were determined. In Sprague-Dawley rats, Gunn rats, and guinea pigs, the rate of excretion of radioactivity was dependent upon the administered dose. Excretion and tissue distribution of radioactivity were qualitatively similar among these species although quantitative differences were observed. In hamsters, the rate of excretion was essentially independent of dose at the concentrations examined (0.16 and 350 micrograms). The major difference between hamsters and the other species was that increased amounts of radioactivity were retained in lungs of hamsters at the lower dose with a proportional decrease in the amount of radioactivity excreted into bile. The types and relative amounts of conjugated and nonconjugated metabolites of B[a]P were similar in bile of Sprague-Dawley rats and hamsters. Smaller amounts of glucuronides and larger amounts of sulfate conjugates were detected in bile of Gunn rats than in bile of Sprague-Dawley rats or hamsters. Metabolites in bile of guinea pigs were markedly different from those in the other species in that approximately 90% of the metabolites were thioether conjugates. Buthionine sulfoxime was used to reduce tissue levels of glutathione in Sprague-Dawley rats. When liver and lung glutathione levels were reduced to 30% and 82% of control levels, respectively, the amount of radioactivity excreted into bile was not significantly different from controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888615 TI - Uptake, toxicity, and distribution of benzo[a]pyrene and monooxygenase induction in the topminnows Poeciliopsis monacha and Poeciliopsis lucida. AB - Poeciliopsis lucida and Poeciliopsis monacha are freshwater viviparous fishes susceptible to tumorigenesis by brief exposure to waterborne procarcinogens. The hepatic monooxygenase system and the uptake, toxicity, and distribution of benzo[a]pyrene (BP) were characterized as a first step in exploring relationships between xenobiotic metabolism and cancer in these fishes. Waterborne BP was lethal at a dose of 3.75 mg/liter with a 24-hr exposure. During a 24-hr exposure to 1.0 mg/liter (3.97 mumol/liter) [3H]BP, an average of 8.27 nmol of BP was taken up per fish. Of this total, 64-70% was in the gallbladder or gut, indicating rapid metabolism and excretion. Basal levels of aryl hydrocarbon hydroxylase (AHH) activity were fairly high, about 0.6 nmol/min/mg. Maximal induction by BP occurred at a dose of 1.0 mg/liter, but with AHH activities only about twice the levels in untreated fish. Sensitivity to inhibition by alpha naphthoflavone (ANF) increased slightly in treated fish. Induced AHH and also 7 ethoxyresorufin O-deethylase (EROD) activities declined slowly after a single treatment, approaching pre-exposure levels after 7 days. Monoclonal and polyclonal antibodies to cytochrome P-450E, the AHH and EROD catalyst in the marine fish scup (Stenotomus chrysops), inhibited AHH and EROD activities in untreated Poeciliopsis, indicating structural similarity between the catalysts in these fish species. Untreated Poeciliopsis evidently contain a counterpart to scup cytochrome P-450E, the major polycyclic aromatic hydrocarbon-inducible from in scup. High levels of basal activity and the pattern of monooxygenase induction could be involved in the sensitivity of these fishes to polycyclic aromatic hydrocarbon and other procarcinogens. PMID- 2888617 TI - The metabolism and elimination of pyrilamine maleate in the rat. AB - The metabolism and elimination of pyrilamine (2-[(2-dimethylamino-ethyl)(p methoxybenzyl)amino]pyridine) were characterized after the iv administration of 7.0 mg/kg or 0.7 mg/kg pyrilamine maleate plus [14C]pyrilamine maleate to adult male Fischer-344 rats. Approximately 29% and 38% of the administered dose was excreted in the urine in the first 24 hr in the high and low dose groups, respectively, as determined by liquid scintillation spectrometry. Fecal excretion accounted for 27% and 30% of the administered dose in the first 24 hr in the high and low dose groups, respectively, as confirmed via combustion analysis. The 24 hr urinary metabolic products consisted of one major and four minor radiolabeled compounds. The major metabolite was isolated by reversed-phase high performance liquid chromatography and identified as the O-glucuronic acid conjugate of O demethyl pyrilamine. This was accomplished by comparison of the chromatographic characteristics of this metabolite's aglycon with that of an authentic standard of O-demethyl pyrilamine and fast atom bombardment mass spectrometry of the unhydrolyzed conjugate. Pyrilamine and its N-oxide and O-demethyl derivatives were also identified after isolation by reversed-phase high performance liquid chromatography and comparison of their mass spectral and/or chromatographic properties with those of authentic compounds. The plasma metabolic profile was essentially the same as the urinary profile except for the absence of O-demethyl pyrilamine. The plasma elimination of pyrilamine fit a one-compartment open model and was first order. The terminal plasma elimination half-life of pyrilamine did not increase with increasing doses (2.3 hr, 0.7 mg/kg; 1.5 hr, 7.0 mg/kg) and thus pyrilamine does not exhibit dose-dependent elimination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888616 TI - Determination of metabolite pharmacokinetics for orally administered prodrugs. AB - The theoretical evaluation of a pharmacokinetic precursor/metabolite model was accomplished utilizing an integral approach based on clearance. Particular attention was paid to prodrugs where a single active intermediate results directly from the parent drug. This model, however, can be utilized for any drug in which a single first-pass metabolic adduct results. Complete elucidation of the first-pass and metabolic systemic pharmacokinetics is possible when plasma and urine concentration data are available after only oral drug administration. The generality of the model does not require prior knowledge of whether the metabolite was formed systemically or presystemically, and only limited metabolic pathway profiling. The model was applied to the evaluation of the angiotensin converting enzyme inhibitor prodrug pentopril. PMID- 2888618 TI - N-debenzylation of pyrilamine and tripelennamine in the rat. A new metabolic pathway. AB - Male Sprague-Dawley rats received 20 mg/kg of pyrilamine or tripelennamine intraperitoneally. The extract obtained from an enzymatically hydrolyzed urine was derivatized with or without Tri-Sil Z and analyzed by GC/MS. 2-(2 Dimethylaminoethyl)aminopyridine, 2-(4-hydroxybenzyl)aminopyridine, 2-[4 hydroxybenzyl-(2-dimethylaminoethyl)amino]pyridine, 2-[4-hydroxybenzyl-(2 methylaminoethyl)amino]pyridine, 2-[4-hydroxy-3-methoxybenzyl-(2 dimethylaminoethyl)amino]pyridine, and 2-[3-hydroxy-4-methoxybenzyl-(2 dimethylaminoethyl)amino]pyridine were detected as metabolites of pyrilamine. 2 (2-Dimethylaminoethyl)aminopyridine, 2-(alpha-hydroxybenzyl)aminopyridine, 2 [alpha-hydroxybenzyl-(2-dimethylaminoethyl)amino]pyridine, 2-[4-hydroxybenzyl-(2 dimethylaminoethyl)amino]pyridine, 2-[4-hydroxy-3-methoxybenzyl-(2 dimethylaminoethyl)amino]pyridine, and 2-[3-hydroxy-4-methoxybenzyl-(2 dimethylaminoethyl)amino]pyridine were detected as metabolites of tripelennamine. Thus, N-debenzylation of tripelennamine and N-demethoxybenzylation of pyrilamine occurs in vivo, through an intermediate of alpha-carbon oxidation and represents a new metabolic pathway for these compounds. The identity of the metabolite was confirmed by comparison with an authentic sample of 2-(2 dimethylaminoethyl)aminopyridine. The pharmacological implication of 2-(2 dimethylaminoethyl)aminopyridine, one of the metabolites of pyrilamine and tripelennamine, is discussed. PMID- 2888619 TI - Species-dependent glucuronidation of drugs by immobilized rabbit, rhesus monkey, and human UDP-glucuronyltransferases. AB - The utility of immobilized microsomal enzymes from rabbit liver for the synthesis of a variety of conjugated drug metabolites has been demonstrated in our laboratory. Here, this capability is extended to microsomal preparations from monkey and human liver. A comparative study of glucuronidation of various substrates was carried out using immobilized uridine-5' diphosphoglucuronyltransferase from rabbit, rhesus monkey, and human liver. The three drugs used for the study (sulfadimethoxine, oxazepam, and cyproheptadine) were chosen on the basis of their previously reported in vivo species differences in glucuronidation. Aglycons were incubated with UDP-glucuronic acid in the presence of immobilized UDP-glucuronyl-transferase at pH 7.4 for 16 hr at 37 degrees C. Glucuronide products were purified by high performance liquid chromatography and further characterized by thin layer chromatography and mass spectometry. Species-dependent glucuronidation was observed in all three cases. Differences in the in vitro product formation paralleled in vivo species differences for the three drugs studied. The same glucuronides were produced by immobilized human liver microsomes as have been found to be formed in vivo from the three drugs studied. PMID- 2888620 TI - Metabolism and disposition of ethylene glycol monobutyl ether (2-butoxyethanol) in rats. AB - Ethylene glycol monobutyl ether (2-butoxyethanol, BE) is a major industrial chemical with multiple and diverse uses that may result in significant risk of human exposure and environmental contamination. The current studies were undertaken to investigate the metabolism and disposition of this chemical in male F344 rats. Data presented in this report showed that BE is rapidly absorbed after gavage administration, metabolized, and eliminated. Tissue distribution of BE revealed that BE is distributed to all tissues with the highest levels (determined 48 hr after dosing) detected in the forestomach followed by the liver, kidney, spleen, and the glandular stomach. However, the increase in the tissue concentration in rats treated with 500 mg/kg (as compared to that in rats treated with 125 mg/kg BE) was not proportional to the increase in BE dose. The major route of BE elimination was in the urine, followed by 14CO2 exhalation. The portion of the BE dose eliminated in urine or as 14CO2 was significantly higher in rats treated with 125 mg/kg than in the rats treated with 500 mg/kg. This may indicate that saturation of BE-metabolizing enzymes occurs at the high dose. A small portion (8%) of the administered dose (500 mg/kg) was excreted in the bile in 8 hr after dosing. Qualitative and quantitative HPLC analysis of the urinary and biliary metabolites of BE revealed that the major urinary metabolite, butoxyacetic acid (BAA), accounted for more than 75% of the radioactivity excreted in the urine. The second major metabolite in urine was the glucuronide conjugate of BE (BEG).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888621 TI - Phencyclidine iminium ion. NADPH-dependent metabolism, covalent binding to macromolecules, and inactivation of cytochrome(s) P-450. AB - The phencyclidine iminium ion (PCP-Im+), a potentially reactive 2,3,4,5 tetrahydropyridinium species, is formed by the cytochrome(s) P-450-catalyzed alpha-carbon oxidation of phencyclidine (PCP), a commonly abused psychotomimetic agent. Incubation of PCP-Im+ with liver microsomes obtained from phenobarbital induced rabbits resulted in over 50% loss of microsomal N-demethylase activity and 30% reduction in cytochrome(s) P-450 content. These effects were concentration-dependent, irreversible, and exhibited pseudo-first order kinetics, characteristics of a mechanism-based enzyme inactivation process. Incubation of 3H-PCP-Im+ with liver microsomes resulted in covalent binding of radioactive material to macromolecules by a process that also was NADPH-dependent. PCP-Im+ was metabolized by liver microsomes in the presence of NADPH and this metabolism was inhibited by SKF 525A and carbon monoxide. HPLC analysis has led to the preliminary characterization of an oxidized metabolite of PCP-Im+ which also is formed from PCP. These results support the proposal that this tetrahydropyridinium metabolite of PCP is biotransformed in a cytochrome(s) P-450 catalyzed reaction to form reactive species capable of covalent interactions with biomacromolecules. PMID- 2888622 TI - Stereoselectivity of naphthalene epoxidation by mouse, rat, and hamster pulmonary, hepatic, and renal microsomal enzymes. AB - Previous studies have demonstrated the formation of three glutathione conjugates during the hepatic and pulmonary microsomal metabolism of naphthalene in the presence of reduced glutathione and cytosolic enzymes containing the glutathione transferases. These glutathione conjugates now have been identified by negative ion fast atom bombardment mass spectrometry, by proton NMR spectroscopy, and by chemical synthesis from the (1S,2R)- and (1R, 2S)-naphthalene 1,2-oxide enantiomers as isomeric hydroxyglutathionyldihydronaphthalene derivatives. All three glutathione adducts yielded prominent mass spectral ions at m/z 450 (M-H)-, 432 (dehydration product), and 306 (glutathionyl moiety) which were consistent with the monoglutathionyl derivatives of hydroxydihydronaphthalene. Signals in the proton NMR spectra at 3.60 and 4.95 ppm (adduct 1) and 3.60 and 4.95 ppm (adduct 2) indicated that these conjugates were diastereomers of 1-hydroxy-2 glutathionyl-1,2-dihydronaphthalene. Corresponding signals for H1 and H2 at 4.22 and 4.45 ppm for adduct 3 showed that this isomer was generated from attack of glutathione at the 1 position of the naphthalene 1,2-oxide. Incubation of synthetic (1S, 2R)-naphthalene 1,2-oxide with glutathione in the presence of glutathione transferases resulted in the formation of adducts 1 and 3 in approximately equal proportions; under identical conditions, glutathione conjugate 2 was formed from (1R, 2S)-naphthalene 1,2-oxide. Incubation of naphthalene, glutathione, and glutathione transferases with pulmonary, hepatic, or renal microsomal preparations from mouse, rat, and hamster resulted in the formation of all three glutathione conjugates. Substantial differences in the rates of formation of the individual conjugates were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888623 TI - Comparative defluorination and cytochrome P-450 loss by the microsomal metabolism of fluoro- and fluorochloroethenes. AB - Halogenated ethenes are oxidatively metabolized by cytochrome P-450 to intermediates which inactivate cytochrome P-450 by destroying heme and to epoxides which may react with cellular macromolecules or decompose to other products. To determine the relative capabilities of fluoroethenes to inactivate cytochrome P-450 and undergo metabolism, fluoride release, cytochrome P-450 loss, and heme loss due to the metabolism of trifluorochloroethene (TFCE), chlorodifluoroethene (CDE), difluoroethene (DFE), and trifluoroethene (TFE) were compared in rat hepatic microsomes. Fluoride release, in order of decreasing amounts of fluoride released, followed the order: CDE greater than TFCE much greater than TFE greater than DFE. In contrast, in order of each compound's decreasing effectiveness to destroy both cytochrome P-450 and heme, the following sequence was obtained: TFE greater than CDE greater than TFCE greater than DFE. In phenobarbital-induced hepatic microsomes, TFE inactivated up to 67% of the cytochrome P-450, whereas DFE inactivated only up to 17%. The results of this study indicate that chloro substituents enhance defluorination of the ethenes, and that cytochrome P-450 inactivation by the fluoroethenes is highly dependent on the degree and nature of the halogen substituents. PMID- 2888624 TI - Noncovalent binding of 3'-methyl-N,N-dimethyl-4-aminoazobenzene and its metabolites to liver cytosolic proteins and its role in their nuclear translocation. AB - When liver cytosol prepared from rats administered [14C]3'-methyl-N,N-dimethyl-4 aminoazobenzene was subjected to Sephadex gel chromatography, four peaks (I-IV) of radioactivity containing proteins and one peak (V) of radioactivity devoid of protein were obtained. Forty to fifty-five per cent of the radioactivity in the protein peaks was butanol-extractable. When the protein peaks were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, over 90% of the radioactivity was separated from the proteins, indicating lack of covalent binding. Several differences in the metabolite patterns were seen when the butanol-extractable metabolites from the five chromatographic peaks were analyzed by TLC. When pooled fractions of the peaks were incubated with isolated rat liver nuclei, only radioactivity associated with peak II was translocated into the nucleus. Translocation was time- and temperature-dependent and was maximal at 40 min at 37 degrees C. Only 10 to 12% of the radioactivity associated with peak II could be translocated even in the presence of an excess of nuclei, indicating that specific protein metabolite adduct(s) present in this fraction is/are translocated. Five per cent of translocated radioactivity was irreversibly bound to DNA, 3% to RNA, 67% to non-histone proteins, and 7.5% to histones; the remaining was not associated with any of these macromolecules. PMID- 2888625 TI - Effect of cytochrome P-450 and flavin-containing monooxygenase modifying factors on the in vitro metabolism of amiodarone by rat and rabbit. AB - Experiments were conducted to affirm hepatic cytochrome P-450 involvement in the biotransformation of the class III antiarrhythmic agent, amiodarone (Am; Cordarone X) to its major metabolite, desethylamiodarone (DEA). Male Sprague Dawley rats and male New Zealand white rabbits were treated with phenobarbital (PB) or 3-methylcholanthrene (3-MC) (to induce cytochrome P-450 (PB-inducible cytochrome(s) P-450) or P-448 (MC-inducible cytochrome P-450). In vivo decreases in rat hepatic microsomal cytochrome P-450 were achieved either by a single ip dose of CCl4 or by a 2-day treatment with CoCl2. In vitro biotransformation of Am by hepatic microsomes from PB-induced and 3-MC-induced rats and PB-induced rabbits was significantly greater than that from noninduced animals. Conversely, in vitro DEA production was significantly decreased with hepatic microsomes from CCl4- and CoCl2-pretreated rats. The classic P-450 inhibitors, piperonyl butoxide, SKF 525A, n-octylamine, and CO provided a significant reduction in the in vitro formation of DEA by microsomes from induced animals. In vitro DEA formation by hepatic microsomes from PB- and 3-MC-induced rats was significantly decreased by 0.5 mM chloroquine (specific inhibitors of PB-inducible cytochrome(s) P-450) and 0.3 mM quinacrine (specific inhibitor of MC-inducible cytochrome(s) P-450), respectively. Further evidence for involvement of gut microsomal flavin-containing monooxygenase was provided by the inhibition of gut microsomal-mediated in vitro DEA formation in the presence of methimazole. Methimazole had no effect on hepatic microsomal DEA production in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888626 TI - Effects of genetic or chemically induced diabetes on imipramine metabolism. Respective involvement of flavin monooxygenase and cytochrome P-450-dependent monooxygenases. AB - Imipramine metabolism has been studied in both type I (streptozotocin-induced insulin-deficient) and type II (genetically insulin-resistant) diabetes in mice. In both types of diabetes, the formation of imipramine N-oxide is increased. In type I diabetes, desmethyl- and 2-hydroxyimipramine are additionally increased. The inhibition of imipramine metabolism by anti-cytochrome P-450 reductase antibodies led to the conclusion that cytochrome P-450-dependent monooxygenases are not involved in the N-oxidation of imipramine. This metabolic route is only supported by the flavin monooxygenase, whose activity is increased by diabetes. The pharmacological implications of altered imipramine metabolism in diabetic states are discussed in relation to the drug metabolism in human diabetes. PMID- 2888627 TI - Stereoselective metabolism of 2-phenylpropionic acid in rat. I. In vitro studies on the stereoselective isomerization and glucuronidation of 2-phenylpropionic acid. AB - Optical isomerization of 2-phenylpropionic acid (hydratropic acid, HTA) was studied in the organs of male rat in vitro. (R)-(-)-HTA was not isomerized by rat liver homogenate even after the addition of CoA, ATP, and Mg2+ to the incubation mixture; however, it was isomerized slowly but significantly in liver slices. This suggests that some additional factor(s) are required for the optical isomerization of HTA in rat liver homogenate. Kidney slices showed about 3-fold higher isomerizing activity of (R)-(-)-HTA than liver slices. (S)-(+)-HTA was also slightly isomerized to (R)-(-)-HTA in kidney slices suggesting that the isomerization of HTA is stereoselective but not stereospecific. The liver and the kidney were considered to be the major organs for isomerization of HTA, since the isomerizing activity of the small intestine was low and other tissues examined were inactive. Change of the incubation medium of liver slices from Krebs-Ringer bicarbonate buffer to Krebs-Ringer buffer without bicarbonate, 0.25 M sucrose solution with 0.05 M Tris-HCl buffer (pH 7.4) or 0.9% NaCl solution with 0.05 M Tris-HCl buffer (pH 7.4) increased the isomerization rate of (R)-(-)-HTA to (S) (+)-HTA, but decreased the glucuronide formation. During incubation of racemic HTA with liver slices, (S)-(+)-enantiomer percentage in HTA acyl glucuronide (HTA G) increased with time, whereas that of the free HTA remained nearly constant. These results suggested the stereoselective hydrolysis of (R)-(-)-HTA-G in liver slices, which was confirmed by the results from incubation of HTA-G with rat liver preparations. Kidney homogenate also preferentially hydrolyzed (R)-(-)-HTA G. PMID- 2888628 TI - Stereoselective metabolism of 2-phenylpropionic acid in rat. II. Studies on the organs responsible for the optical isomerization of 2-phenylpropionic acid in rat in vivo. AB - The contribution of the liver and kidney to the optical isomerization of (R)-(-) 2-phenylpropionic acid (hydratropic acid (HTA] was examined by iv injection of racemic HTA (20 mg/kg) to nephrectomized and bile duct-ligated rats (NEBL-rats), eviscerated rats with nonfunctioning livers (EVIS-rats), rats with ligated bilateral ureters and bile ducts (BUBL-rats), and sham-operated rats. The decrease of (R)-(-)-enantiomer percentage of HTA in plasma of EVIS-rats from 53% (5 min) to 45% (60 min) clearly proved the contribution of the kidney on the optical isomerization of (R)-(-)-HTA in vivo. In NEBL-rats, the decrease of (R)-( )-enantiomer percentage of HTA in plasma was only 2% in 55 min, but the (R)-(-) enantiomer percentages of HTA acyl glucuronide (HTA-G) in plasma and liver at 1 hr after dosing were 40% and 30%, respectively. Therefore, the contribution of the liver on the isomerization was also suggested. Only a trace amount of HTA-G was detected in the EVIS-rats plasma and kidney, confirming the low glucuronic acid-conjugating activity of HTA in rat kidney. But, in the BUBL-rats, stereoselective hydrolysis of (R)-(-)-HTA-G in the kidney was suggested. Both the stereoselective glucuronidation of (S)-(+)-HTA and the stereoselective hydrolysis of (R)-(-)-HTA-G in rat liver might be responsible for the enrichment of (S)-(+) HTA-G in the liver. PMID- 2888629 TI - Physiologically based pharmacokinetics of radioiodinated human beta-endorphin in rats. An application of the capillary membrane-limited model. AB - In order to simulate the distribution and elimination of radioiodinated human beta-endorphin (125I-beta-EP) after iv bolus injection in rats, we proposed a physiologically based pharmacokinetic model incorporating diffusional transport of 125I-beta-EP across the capillary membrane. This model assumes that the distribution of 125I-beta-EP is restricted only within the blood and the tissue interstitial fluid, and that a diffusional barrier across the capillary membrane exists in each tissue except the liver. The tissue-to-blood partition coefficients were estimated from the ratios of the concentration in tissues to that in arterial plasma at the terminal (pseudoequilibrium) phase. The total body plasma clearance (9.0 ml/min/kg) was appropriately assigned to the liver and kidney. The transcapillary diffusion clearances of 125I-beta-EP were also estimated and shown to correlate linearly with that of inulin in several tissues. Numerically solving the mass-balance differential equations as to plasma and each tissue simultaneously, simulated concentration curves of 125I-beta-EP corresponded well with the observed data. It was suggested by the simulation that the initial rapid disappearance of 125I-beta-EP from plasma after iv injection could be attributed in part to the transcapillary diffusion of the peptide. PMID- 2888630 TI - The metabolism of roxatidine acetate hydrochloride. Liberation of deuterium from the piperidine ring during hydroxylation. AB - The metabolism of roxatidine acetate hydrochloride (RA), a new histamine-2 receptor antagonist, was studied by GC/MS in rats and dogs in vivo. The co administration of 14C-RA and RA-d10 labeled with deuterium in the piperidine ring expedited the isolation and identification of 15 urinary metabolites. The major metabolites in both animals were M-1, M-8, M-10, and M-11; M-4 could be found only in the rat. The aromatic and piperidine ring-hydroxylated metabolites were found in small amounts in both species. Following the administration of RA-d10 to rats and dogs, oxygenated metabolites on the piperidine ring, such as M-3 and M 4, were isolated and their analysis indicated the unexpected loss of three or four deuterium atoms from the ring. Also, first and second isotope effects were observed on the conversion rate in vivo and retention time in HPLC, respectively. PMID- 2888631 TI - 6-Fluoro-2-methylspiro(chroman-4,4'-imidazolidine)-2',5'-dione and related compounds as inducers of monooxygenase in rat liver microsomes. AB - The relationship between the structure of spirohydantoin derivatives and their inducing effects on hepatic monooxygenase system was studied. At the dose of 1 mumol/kg (0.3 mg/kg), 6-fluoro-2-methylspiro(chroman-4,4'-imidazolidine)-2',5' dione (M79175) was found to exhibit an inducing effect on benzphetamine N demethylase. On the contrary, the inducing effect of Sorbinil, in which the 2 methyl group on the chroman ring of M79175 was replaced by hydrogen atom, on benzphetamine N-demethylase was 100 times less than that of M79175. The substitution of the methyl group of M79175 with the dimethyl group did not affect the inducing effect, whereas the substitution with the hexyl group resulted in the loss of the inducing effect on drug oxidation activities tested at a dose of 10 mg/kg. Furthermore, cyclohexane spiro-2,6-chloro-1'-(3 dimethylaminopropyl)spiro(chroman-4,4'-imidazolid ine)-2' , 5'-dione (M79193) had an inducing effect on total cytochrome P-450 content, but had no inducing effect on benzphetamine N-demethylase. In addition, M79175 was found to induce cytochrome P-450 which is immunochemically related to one of the major forms of phenobarbital-inducible cytochrome P-450 (P-450(PB-1], but not cytochrome P-450 which is immunochemically related to the major form of 3-methylcholanthrene inducible cytochrome P-450 (P-450(MC-1]. On the other hand, M79193 was found to induce neither P-450(PB-1) nor P-450(MC-1). PMID- 2888633 TI - Inhibition and induction of hepatic drug metabolism in rats and mice by nafimidone and its major metabolite nafimidone alcohol. AB - Nafimidone, a candidate anticonvulsant agent, and its metabolite (nafimidone alcohol) demonstrated potent inhibition of hepatic drug metabolism in male rats. Inhibition occurred both in vivo following acute administration as a prolongation of hexobarbital sleeping time and as an elevation of plasma hexobarbital levels, and in vitro following addition to hepatic microsomes as a disruption of ethyl morphine N-demethylation and aniline p-hydroxylation. Inhibition of ethylmorphine N-demethylation was of a mixed type, whereas aniline p-hydroxylation was inhibited in a noncompetitive manner; the micromolar Ki values obtained for both enzymes were severalfold lower than those obtained for imidazole. Nafimidone alcohol produced a type II difference spectrum when added to rat hepatic microsomes. The Ks value was 2.1 microM. Chronic administration of nafimidone alcohol caused induction of hepatic drug metabolism typified by shortening of pentobarbital sleeping time in vivo in male mice and a doubling of hepatic microsomal cytochrome P-450 content in male rats. In rats, these changes were associated with a 30-fold elevation in the Vmax for microsomal ethoxyresorufin O deethylase and a moderate increase in the Vmax for microsomal ethylmorphine N demethylase, but no change in either the rate of aniline p-hydroxylation, 4 hydroxybiphenyl- or 4-methylumbelliferone UDP-glucuronosyltransferase, or the activity of the flavoprotein reductase component. These data suggest induction of a predominating cytochrome P-448-type of Phase I drug-metabolizing activity by nafimidone alcohol. PMID- 2888632 TI - Disposition of nafimidone in rats. AB - The absorption, distribution, excretion, and metabolism of 14C-nafimidone, a novel anticonvulsant, have been studied in rats. Nafimidone was completely absorbed following single oral doses of 10 and 100 mg/kg. After both iv and oral administration, nafimidone was rapidly eliminated from plasma (t 1/2 about 5 min), with concomitant formation of a pharmacologically active, nonconjugated metabolite, nafimidone alcohol. Systemic clearance of nafimidone from plasma after iv administration was approximately 2 times higher than hepatic blood flow in rats, and the oral bioavailability was 15%. However, the AUC of nafimidone alcohol was 30% higher after oral administration of nafimidone than that after iv administration of nafimidone. It is likely that, given its pharmacological activity, nafimidone alcohol is the more important species pharmacologically. Distribution of nafimidone-related radioactivity was widespread with highest concentrations associated with liver, kidney, adrenals, and the gastrointestinal tract. Elimination of radioactivity from tissues was rapid and complete, except that retention was noted in arterial vessels and in the ocular melanin of pigmented rats. Determination of hepatic and brain levels of nafimidone and nafimidone alcohol showed no detectable levels of nafimidone in either tissue. However, levels of nafimidone alcohol in liver and brain were as much as 13-fold and 2-fold, respectively, higher than levels in plasma. After either iv or oral administration of 14C-nafimidone, approximately two-thirds of the radioactivity was recovered in urine. The major urinary metabolites of nafimidone after a 100 mg/kg dose were characterized and shown to be dihydroxydihydronaphthalene, substituted nafimidone alcohol, and the 1-beta-glucuronide of nafimidone alcohol. PMID- 2888634 TI - The metabolic fate of oxazepam in mice. PMID- 2888635 TI - Formation of the taurine conjugate of benzoic acid in rainbow trout, Salmo gairdneri. PMID- 2888636 TI - A phenolic metabolite of phencyclidine: the formation of a pharmacologically active metabolite by rat liver microsomes. PMID- 2888637 TI - Evaluation of temazepam and diphenhydramine as hypnotics in a nursing-home population. AB - Seventeen nursing home residents with sleeping problems were enrolled in a randomized, double-blind, crossover trial of temazepam 15 mg, diphenhydramine (DPH) 50 mg, and placebo. Each drug was given for five consecutive nights with a 72-hour washout period between drugs. Subjects were assessed three times weekly with tests of psychomotor and cognitive function and four times weekly with observer sleep diaries and morning sleep questionnaires. Three subjects failed to complete the study. By report of the subjects, DPH resulted in shorter sleep latency than did placebo (t = 2.77, p less than 0.05). On the fifth night, use of DPH was associated with longer duration of sleep than temazepam (t = 2.88, p less than 0.05). No significant difference in tests of neurologic function was noted although, compared with placebo, subjects performed more poorly on seven of eight tests while taking temazepam and five of eight tests while taking DPH. Several instances of daytime hypersomnolence were noted in subjects taking temazepam and DPH, but none in subjects given placebo. PMID- 2888638 TI - Effect of ranitidine on chloroquine disposition. AB - Ten healthy, male volunteers (aged 19-27 yr; weight 62-67 kg) were randomly distributed into control and test groups of five subjects each in a controlled study on the effect of ranitidine on chloroquine disposition. The control group subjects received two tablets of chloroquine sulfate (300-mg base) only. The test group subjects received ranitidine 250 mg hs for four days prior to the administration of chloroquine sulfate and throughout the sample collection period. Blood samples (5 ml) were collected from the time of the chloroquine administration to the seventh day after drug administration. The samples were analyzed for chloroquine content by a combination of thin-layer chromatography and ultraviolet spectrophotometry. The Wilcoxon test at 0.05 significance level was used to compare the disposition parameters between control and test groups. Ranitidine therapy was associated with no significant alterations in chloroquine oral clearance rate, elimination rate constant, and apparent volume of distribution. Unlike cimetidine, ranitidine does not interact pharmacokinetically with chloroquine. Ranitidine, therefore, may be the H2-receptor antagonist of choice for ulcer patients receiving chloroquine. PMID- 2888639 TI - Fate map of the eye-antennal imaginal disc of the tumorous-head mutant of Drosophila melanogaster. AB - In specific genetic backgrounds, a mutation in the tuh-3 gene results in the homeotic transformation of head structures to either leg disc derivatives or structures normally found in the extreme posterior end of wild-type animals. The origins of the homeotic structures were mapped to defined positions in the eye antennal imaginal disc by transplanting abnormal regions of discs isolated from tuh-3 mutants into host mwh;e4 larvae. These metamorphosed implants were removed and differentiated structures were identified. Of 211 successfully recovered implants, 157 gave rise to homeotic tissue: abdominal tergite, male or female external genitalia and/or leg tissue. Transformations to abdominal tergite occurred primarily in cells taken from the eye region of the compound disc. Male and female genitalia arose most often in implants taken from the antennal portion of the disc, although some tissue taken from the lateral region of the eye disc also gave rise to external genitalia. Leg structures came exclusively from implants from the antennal region of the imaginal disc. These results suggest that cells from within specific regions of the eye-antennal compound disc are constrained in their developmental potential. An obvious constraint observed with this mutation is a dorsal/ventral one: Cells from the eye disc, a dorsal structure, primarily gave rise to other dorsal structures, abdominal tergite tissue. Cells from the antennal disc, a ventrally derived structure, primarily gave rise to other ventral structures including genital tissue and distal leg. PMID- 2888640 TI - Differentiation and grafting of haemopoietic stem cells from early postimplantation mouse embryos. AB - Haemopoietic stem cells evidently arise in early post-implantation mouse embryos at day 6 of gestation, a day earlier than previously thought (Moore & Metcalf, 1970). Disaggregated embryonic cells were injected into mice given a lethal dose of X-irradiation. The presence of donor haemoglobin (Whitney, 1978) and donor lymphocytic glucose phosphate isomerase (GPI) (Siciliano & Shaw, 1976) to detect donor erythrocytes and lymphocytes, respectively, were monitored by starch gel electrophoresis. The presence of donor cells was also assessed by using donor embryos carrying the T6 marker chromosomes. Decidual cells dissected free of embryos did not colonize any recipients. Disaggregated cells from early mouse embryos first colonized the liver and then repopulated the haemopoietic systems of recipients, producing adult donor haemoglobin within 2-3 days and donor GPI within 3-5 days. 80% of grafted X-irradiated recipients survived and donor markers were found in each of them. All nongrafted controls died within 14 days of X-irradiation and none of them showed donor markers. Disaggregated embryonic cells could be grafted across major histocompatibility barriers unlike adult bone marrow. Haemopoietic stem cells could not be identified in disaggregated cells from embryos aged less than 6 days gestation. PMID- 2888641 TI - The mitochondrial myopathies. Defects of the mitochondrial respiratory chain and oxidative phosphorylation system. PMID- 2888642 TI - Neurotransmitter amino acids in epilepsy. PMID- 2888643 TI - Mechanisms of anticonvulsant drug action. AB - The actions of clinically used anticonvulsant drugs on sustained high frequency repetitive firing of action potentials and on responses to gamma aminobutyric acid (GABA) have been determined using mouse neurons in cell culture, and a classification of anticonvulsant drug actions has been developed based on these cellular actions. Actions of the anticonvulsant drugs were accepted as clinically relevant only if they occurred at concentrations achieved in cerebrospinal fluid or in plasma unbound to plasma proteins. Based on their cellular mechanisms of actions, drugs have been divided into 3 categories: (1) Phenytoin, carbamazepine and valproic acid limited sustained high frequency repetitive firing but did not alter GABA responses. (2) Phenobarbital and the benzodiazepines, clonazepam, diazepam and nitrazepam, augmented postsynaptic GABA responses. These drugs limited sustained high frequency repetitive firing only at concentrations above the therapeutic range in ambulatory patients, but equal to concentrations achieved in the acute treatment of status epilepticus. (3) Ethosuximide failed to reduce sustained high frequency repetitive firing or enhance GABA responses even at supertherapeutic concentrations. Limitation of sustained high frequency repetitive firing by anticonvulsant drugs correlated well with efficacy against generalized tonic-clonic seizures in man and against maximal electroshock seizures in experimental animals. Enhancement of postsynaptic GABA responses correlated with efficacy against generalized absence seizures in man and against pentylenetetrazol seizures in animals. Ethosuximide, however, did not alter GABA responses or sustained high frequency repetitive firing suggesting that its action against generalized absence seizures in man and pentylenetetrazol seizures in experimental animals occurs by an additional, as yet unknown, mechanism. PMID- 2888644 TI - Biochemical and morphological changes in the aging brain. PMID- 2888645 TI - Cysteamine-induced decrease of somatostatin in rat brain synaptosomes in vitro. AB - The mechanism of somatostatin depletion induced by cysteamine [2 mercaptoethylamine (CySH)] was studied in isolated nerve endings (synaptosomes) from rat brain in vitro. A dose-dependent reduction of somatostatin-like immunoreactivity (SLI) was observed which reached its maximal extent (41%) at a concentration of 300 microM CySH after 1-5 min. There was no release of somatostatin into the incubation medium. CySH at concentrations of up to 10 mM did not interfere in the RIA. Among a variety of compounds, structurally related to CySH 4-aminothiophenol, 2-aminothiophenol and N,N-dimethylaminothiol exhibited the highest efficacy in decreasing somatostatin (60%, 50%, 30%, respectively, at 10 mM and 10 min). The disulfide form of CySH cystamine and dimercaprol resulted in about 15% reduction after 10-min incubation, whereas taurine, alanine, cysteine, and mercaptoethanol were inactive. A saturable, sodium-dependent uptake process was found for the disulfide form of [35S]CySH cystamine [Michaelis-Menten constant (Km) = 18.6 microM, maximum velocity (Vmax) = 2.3 nmol/mg protein X 3 min) which was inhibited by cysteine (87% at 1 mM). [35S]CySH, at concentrations of 20 microM or less, was not stable in buffer solution. It underwent considerable nonenzymatic conversion into its dimeric form (60% at 37 C and 3 min), however it exhibited the same kinetic data for its uptake. Size exclusion HPLC of purified hypothalamic synaptosomes revealed a major SLI peak coeluting with synthetic somatostatin-14 and two minor peaks representing somatostatin-28 and a 13,000 mol wt protein. The three molecular forms of somatostatin were reduced to varied extent by CySH (somatostatin-14 by about 70%, somatostatin-28 by 15%, and the high mol wt form by 30%). Our experiments suggest that high affinity uptake of CySH may precede its action in decreasing somatostatin levels. Increased release or inhibition of synthesis of somatostatin have been excluded as possible mechanisms. It is suggested that SLI is equally affected in nerve endings and in perikarya. PMID- 2888646 TI - Plasma growth hormone (GH) response to intravenous GH-releasing factor (GRF) in adult rats: evidence for transient pituitary desensitization after GRF stimulation. AB - The ability of human (h)GRF-(1-29)NH2 to stimulate GH secretion was studied in cannulated adult rats. In order to suppress endogenous GRF secretion and the inhibitory action of hypothalamic somatostatin (SRIF), rats were anesthetized with sodium pentobarbital. Intravenous administration of hGRF-(1-29)NH2 elicited a dose-dependent response of plasma GH, with 250 ng/kg being the smallest effective dose in male rats. In female rats, for each dose tested (250 to 70,000 ng/kg), the GH response represented only about 60% that of male rats. Repeated iv stimulations with hGRF-(1-29)NH2 at short time intervals (45 min) produced transient desensitization of pituitary responsiveness to GRF: a blunted GH response to the second and third stimulations was observed both in male and in female rats and for each dose tested. Similar blunted responses were also obtained with repeated injections of native hGRF-(1-44)NH2. The possibility that these blunted responses could be due to incomplete suppression of hypothalamic SRIF secretion by sodium pentobarbital was excluded by the use of rats that were passively immunized against SRIF; in these rats, it was shown that at least 65% of the inhibition of the GH response after the second GRF stimulation was unrelated to SRIF action. Similar transient desensitization to repeated hGRF-(1 29)NH2 stimulations was also observed in conscious rats that were passively immunized against SRIF. This occurrence of blunted responses was shown to be related to the length of the time interval between GRF stimulations, with longer intervals resulting in less or no desensitization. It appears thus that modulation of pituitary responsiveness to the action of GRF is mediated by at least two independent mechanisms in the rat: in addition to the inhibitory action imposed by hypothalamic SRIF, which induces periods of refractoriness to the action of GRF, it was shown in this study that in the pituitary level each GRF stimulation also induces a transient desensitization of somatotrophs for about 1 h. This period of refractoriness might not be due to excessive stimulation with GRF, since it was also observed with the lowest dose of hGRF-(1-29)NH2 that gave a significant release of GH. Finally, a sex difference was confirmed for the response of anesthetized adult rats to stimulation with hGRF-(1-29)NH2, reflecting a sex steroid-induced modification of pituitary responsiveness to GRF stimulation. PMID- 2888648 TI - Pre-operative medication reviewed: oral temazepam compared with papaveretum and hyoscine. AB - Oral temazepam was compared with papaveretum and hyoscine for pre-operative medication. The oral premedication was associated with less subjective unpleasant side-effects and greater anxiolytic properties. It was adjudged to be superior by the anaesthetic and nursing staff as well as by the patients themselves. Oral premedication was also less time-consuming to administer, and there was a small saving in the cost of drugs and equipment. PMID- 2888647 TI - The rat posterior pituitary contains a potent prolactin-releasing factor: studies with perifused anterior pituitary cells. AB - We previously reported that removal of the posterior pituitary abolished the suckling-induced rise in plasma PRL. This suggested that the posterior pituitary contains a PRL-releasing factor (PRF). Using perifused anterior pituitary cells, the objectives of this study were 1) to examine whether the posterior pituitary contains PRF activity as compared to the medial basal hypothalamus (MBH), and 2) to determine to what extent substances known to be present in the posterior pituitary and/or MBH contribute to this activity. Anterior pituitary cells, attached to Cytodex beads, were perifused with medium 199. Tissues were extracted with acid, lyophilized, and reconstituted in medium 199. Tissue extracts and synthetic compounds were introduced to the cells in short pulses. Fractions were collected and analyzed for PRL, LH, and GH by RIA. Posterior pituitary extracts contained a potent substance(s) which stimulated PRL release in a concentration dependent manner, but did not alter LH secretion. As little as 1% of the extract increased PRL release. In contrast, the MBH extract contained significantly less PRF activity but was capable of stimulating and inhibiting LH and GH release, respectively. Cerebellar extracts did not alter PRL secretion. Of more than 25 neuroactive substances tested in the perifusion system, oxytocin, TRH, and angiotensin II (A II) appeared as likely candidates for PRF. Therefore, the specific receptor antagonists d(CH2)5Tyr(Me) ornithine vasotocin (for oxytocin), chlordiazepoxide (for TRH), or saralasin (for A II) were infused together with the posterior pituitary extract. These antagonists completely abolished the PRL releasing activities of their respective peptides but failed to reduce the PRF activity of the posterior pituitary. In contrast, PRF activity in the MBH was nearly eliminated by the TRH antagonist. CONCLUSIONS: 1) The rat posterior pituitary contains a potent PRF capable of inducing a rapid, hormone-specific, concentration-dependent stimulation of PRL release from perifused anterior pituitary cells. 2) The MBH contains significantly less PRF activity, which is largely attributable to TRH. 3) Although the chemical identity of PRF is yet unknown, the PRF activity in the posterior pituitary is not accounted for by oxytocin, TRH, or A II. PMID- 2888649 TI - Isoproterenol sensitivity in heat tolerant and relatively heat intolerant men. AB - Recent research has demonstrated that pharmacologic blockade of beta adrenoceptors predisposes to hyperthermia during prolonged exercise. To investigate the hypothesis that beta-adrenoceptor sensitivity to catecholamines may be an important determinant of exertional heat tolerance, we performed a cross-sectional study comparing the heart rate responses to graded doses of isoproterenol in 6 heat tolerant and 6 relatively heat intolerant men. We observed no significant difference (p greater than 0.1) between the heat tolerant (0.9 +/- 0.68 microgram) and heat intolerant (1.19 +/- 0.61 microgram) subjects in the dose of isoproterenol that produced a 25 beat.min-1 increment in heart rate. Although the possibility of a relationship between beta-adrenoceptor sensitivity and the ability to tolerate exercise in heat cannot be entirely excluded on the basis of these data, our study clearly demonstrates the lack of a correlation between cardiac pacemaker sensitivity to isoproterenol and exertional heat tolerance. PMID- 2888650 TI - Role of the essential thiol group in the thiol-activated cytolysin from Clostridium perfringens. AB - A hemolysin, 0-toxin, produced by Clostridium perfringens has one cysteinyl residue in the free thiol form which is essential for its hemolytic activity. The cysteinyl residue was shown to be located at a position about 5 kDa from the C terminus of the molecule by the method of cysteine-specific chemical cleavage. Modification of the residue with a thiol-blocking agent, 5,5'-dithiobis(2 nitrobenzoic acid), reduced the binding affinity of the toxin to sheep erythrocytes to 1/100 that of intact toxin, resulting in a failure of binding at low cell concentrations (0.5%). Thus the failure of hemolysis at low cell concentrations is primarily ascribed to a decreased affinity of the toxin for erythrocytes. Effects of the modification on the lytic processes were examined using high cell concentrations where considerable amounts of modified toxin bound to the cells. The modified toxin hemolyzes erythrocytes once it binds to them; however, the efficiency of hemolysis is reduced by the modification. These, and additional results indicating that modification alters the sensitivity of toxin molecules to protease digestion, show that thiol-modification inactivates the toxin by affecting both binding and the subsequent lytic processes, probably through a conformational change introduced in the toxin molecules. PMID- 2888651 TI - Adenosine-provoked angina pectoris-like pain--time characteristics, influence of autonomic blockade and naloxone. AB - In a study to characterize the time characteristics and the influence of blockade of beta, cholinergic and opioid receptors on the chest pain induced by adenosine, this agent was given as a bolus into a peripheral vein of six healthy volunteers (4 men) 24-45 years of age. On the first day the maximum tolerable dose was determined in each case. On the second day three doses of adenosine (1/3, 2/3, and a full maximum tolerable dose) and three doses of placebo were given as single blind doses in randomized order. Thereafter metoprolol (10 mg to males, 8 mg to females), followed by 1 mg atropine and then 0.4 mg naloxone were given intravenously. After each agent the test procedure was repeated. Heart rate and atrio-ventricular blocks were recorded by electrocardiography and respiration by dynamic spirometry. One minute after each dose of adenosine, the chest pain was scored. The maximum tolerable dose of adenosine was 8.0-15.9 mg. All subjects experienced angina pectoris-like pain. Following injection, onset of respiratory stimulation, AV-block and chest pain occurred after 14 +/- 4.0, 19 +/- 5.4 and 21 +/- 6.4 s, the differences being highly significant. Maximal respiratory stimulation occurred after 18 +/- 4.6, not statistically different from the onset of AV-block which in its turn occurred earlier (P less than 0.005) than the time for maximal central chest pain, 29 +/- 7.8 seconds. Metoprolol induced a 20% slowing of heart rate. After atropine there was a 30% faster heart rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888652 TI - Carotid and coronary artery involvement in infantile periarteritis nodosa possibly induced by Coxsackie B4 infection. Favourable course under corticosteroid treatment. PMID- 2888653 TI - Changes in serum prolactin after electroconvulsive and epileptic seizures. AB - Serial serum prolactin (PRL) concentrations were measured after epileptic seizures and seizures following electroconvulsive therapy (ECT). There was a large and rapid rise in PRL after ECT seizures but a much more variable PRL response after spontaneous seizures. Only epileptic seizures of longer duration and of grand mal character resulted in a more substantial rise in PRL. In ECT seizures there was a significant positive correlation between the duration of seizures and the rise in postictal PRL. The postictal PRL curves over 24 h were similar in both spontaneous seizures and ECT seizures. Interictally there were no difference in PRL levels between epileptic patients compared to patients with other neurological diseases or healthy volunteers. Chronic treatment with drugs affecting dopamine transmission had a profound effect on PRL secretion, and a dose-dependent significant increase in PRL with neuroleptics was observed. PMID- 2888654 TI - Ischemic heart arrest: nitrogenous metabolism in energy-depleted human myocardium. AB - Seventeen patients undergoing radical correction of Fallot's tetrad or defects of interventricular septum were investigated. Needle biopsies from the left ventricular apex region were obtained at the 1st min after cross-clamping of the aorta and at the end of cardiac arrest to determine adenosine triphosphate (ATP), glutamate, aspartate, alanine and ammonia. The losses of ATP during clamping period were related to decrease in glutamate. The fall in ATP by more than 20% of the initial level was accompanied by a significant decrease in aspartate, an accumulation of alanine and ammonia in cardiac tissue but did not affect glutamine content. The data obtained prove the participation of specific nitrogenous compounds of human heart, and especially glutamate, in response to energy depletion during ischemia. PMID- 2888655 TI - Testicular autotransplantation for intraperitoneal cryptorchidism in childhood. A case against neglecting the venous anastomosis. AB - A case of autotransplantation of an intra-abdominal testis into the scrotum in a 9-year-old boy using a microsurgical technique without venous anastomosis is described in detail. The operation failed subsequently due to venous outflow obstruction and the testis underwent atrophy 6 months postoperatively. It was suggested that both the arterial and venous anastomoses may be necessary for the management of this difficult surgical problem. PMID- 2888656 TI - Oncogene amplifications, rearrangements, and restriction fragment length polymorphisms in human leukaemia. AB - We have determined the prevalence of amplification and rearrangements for c-myc, c-myb, c-mos, bcr, c-abl, c-Ha-ras-1, c-N-ras, and c-K-ras-2 in a total of 51 cases of human leukaemia (19 patients with AML, 13 cases with CML, 14 cases with ALL, and 5 cases with CLL). Amplifications at a level of more than 2 two copies per haploid genome are apparently very rare and were found only once for c-myb in a c-ALL patient. Oncogene rearrangements were not found except for bcr, which was rearranged in all cases of CML, and 5 cases of ALL studied. Restriction fragment lengths polymorphisms (RFLPs) were also analysed. A previously described rare 5 kb EcoRI allele at the c-mos locus was absent in our patients. Rare alleles at the c-Ha-ras-1 locus were found to be significantly more prevalent in our patients than in a control group. Transfection experiments revealed no dominant transforming oncogenes in the tumour DNA of 3 patients carrying such rare alleles. PMID- 2888657 TI - Characterization of gamma-glutamyltransferase from neoplastic and non-neoplastic liver tissues in man and during rat liver hepatocarcinogenesis. AB - The activity and the affinity for concanavalin A-Sepharose (Con A) of liver gamma glutamyltransferase (gamma GT) were investigated in man, under various clinical conditions and in rats during experimental hepatocarcinogenesis. In man, gamma GT activity was higher than normal in hepatomas and (except for 1 case of hemochromatosis) also higher in the surrounding cirrhotic liver. The proportion of gamma GT which did not bind to Con A (Con A- form) was also increased in the tumors and in the surrounding liver, yet (with the same exception as above) to a greater extent in the hepatomas. In rat, gamma GT activity was higher in fetal liver (15-fold) and in hepatocarcinomas (10-fold) than in normal adult liver; total liver gamma GT activity gradually increased during progression from foci of altered cells to neoplastic nodules and tumors. The proportion of the Con A- form of gamma GT in the early or late stage of the carcinogenic process did not significantly differ from that in normal adult or regenerating rat liver, i.e. about 20% of the total activity. By contrast, nearly all the gamma GT from fetal rat liver bound to Con A. This suggests that gamma GT expression in rat liver carcinoma does not correspond to so-called retrodifferentiation process. PMID- 2888658 TI - Action of mifentidine on the secretory response to sham feeding and pentagastrin and on serum gastrin in duodenal ulcer patients. AB - A study has been done in 10 duodenal ulcer patients of the effect of a single oral dose of 10 mg mifentidine on the acid and pepsin responses to sham feeding after 1 h 30 min and to pentagastrin after 4 h 15 min. The study followed a double-blind, randomized, placebo-controlled, cross-over design. Gastric juice was collected for 5 h 15 min after treatment. Blood was sampled for up to 3 h 30 min to determine the effects of mifentidine on serum gastrin. Mifentidine suppressed basal acid output by 77% and sham feeding-stimulated acid output by 71% vs the placebo values. Pentagastrin-stimulated acid output was inhibited by 30% throughout the pentagastrin infusion. The suppressant effect of the drug on pepsin output was not as marked as on acid secretion. Mifentidine did not affect the serum gastrin level during the basal and sham feeding phases. No untoward effects were reported by the patients. The results show that 10 mg mifentidine p.o. produced a large reduction in the acid output in response to sham feeding and pentagastrin without affecting the serum gastrin responses. PMID- 2888659 TI - Histamine-producing cell-stimulating activity. A biological activity shared by interleukin 3 and granulocyte-macrophage colony-stimulating factor. AB - The histamine-producing cell-stimulating factor (HCSF) was first described as a lymphokine which is produced during secondary mixed leukocyte culture and which induces increased histamine synthesis by murine hematopoietic cells. It has been shown that it is different from interleukin 3 (IL 3), despite the fact that pure IL 3 expresses HCSF activity. Our results provide evidence that this factor (constitutively produced by the P388 D1 cell line) is identical with granulocyte macrophage colony-stimulating factor (GM-CSF) i.e.: (a) physiochemical properties of HCSF and GM-CSF, such as molecular weight, isoelectric charge, hydrophobicity and behavior during affinity chromatography, are indistinguishable and both activities coelute during all biochemical purification procedures; (b) increased bone marrow cell histamine synthesis induced by P388 D1-derived HCSF is inhibited by anti-GM-CSF antiserum; (c) the GM-CSF cDNA probe hybridizes with a poly(A)+RNA from P388 D1 cells while no hybridizing signal was obtained with poly(A)+RNA from WEHI-3 and from P815 cells. On the other hand, the IL 3 cDNA probe hybridizes with a 1.0-kb poly(A)+RNA from WEHI-3 but not with those from P388 D1 and P815. Moreover, well known sources of GM-CSF, such as lung conditioned medium and semi purified GM-CSF from phytohemagglutinin-induced supernatant of the murine T lymphoma LBRM-33-5 A4 (preparation devoid of IL 3), as well as recombinant murine GM-CSF, induce increased histamine synthesis by hematopoietic cells. All these results demonstrate that, in our culture conditions, the P388 D1 cell line spontaneously produces GM-CSF which is responsible for the P388 D1-induced HCS activity. Consequently, the latter is a property shared by the two distinct hematopoietic growth factors acting on the less committed cells, i.e. IL 3 and GM CSF, whereas M-CSF or G-CSF are unable to induce histamine production. Interestingly, IL-4 which is known to support established mast cell line proliferation cannot induce HCS activity. In addition, none of the other cytokines tested, such as IL 1, IL 2, interferons or tumor necrosis factor can express HCS activity. This expression seems to be a specific property of IL 3 and GM-CSF. PMID- 2888660 TI - Immunoglobulin VH region genes of the mouse are organized in overlapping clusters. AB - Restriction fragment length polymorphism has been compared between the Igh loci of C57BL/6 and MOLF/EI (Mus musculus molossinus) mice utilizing probes which detect the C gamma 2b gene and genes from nine VH-gene families. Distinct restriction site patterns were found for the CH genes and for VH families PC7183, Q52 and X24. VH families V31 and J558 showed identical patterns. Mixed patterns of identical and distinct bands were detected in VH families S107, J606, V3660 and VGAM3.8. This indicates that a recombination took place involving the Igh loci of a M. m. molossinus and a progenitor of the C57BL/6 strain. The breakpoint of recombination maps to the chromosomal region carrying VH families S107, J606, VGAM3.8 and V3660. VH families PC7183, Q52 and X24 map 3' to the recombination breakpoint and proximal to the DH-JH-CH region, whereas VH families V31 and J558 accordingly map 5' to the recombination breakpoint and distal to DH-JH-CH. This order of VH families was confirmed by deletion mapping utilizing hybridomas which are haploid either for the Ighb or for the Igha locus. The mapping data indicate that the VH families of the mouse are organized in overlapping clusters. This notion is confirmed by demonstration of the physical linkage of VH genes from families V31 and J558 in the Igha locus. PMID- 2888661 TI - Differential effects of heroin on opioid levels in the rat brain. AB - Dependence on the potent narcotic agent heroin in rats was produced by the implication of double-coated pellets. Chronic administration of this drug induced significant alterations in dynorphin B and [Met5]enkephalin-Arg6-Gly7-Leu8 (ME RGL) levels in discrete areas of the rat brain. The level of the latter increased by 53.6% in the substantia nigra while the levels of dynorphin B increased in the globus pallidus and ventral tegmental area (188.0 and 41.8%, respectively). PMID- 2888662 TI - Guinea-pig vas deferens preparation may contain both receptors and phencyclidine receptors. AB - Electrically induced contractions of guinea-pig vas deferens were potentiated by sigma drugs such as d-pentazocine and d-SKF-10047 and also by phencyclidine-like drugs. Non-sigma drugs like morphine, buprenorphine, DADLE, U-50488 and l ketocyclazocine did not potentiate contractions. The potentiations were antagonized by haloperidol and BW234U. Although the potentiation may not be definitively mediated by sigma receptors or phencyclidine receptors alone, the preparation may provide an interesting tool for studying endogenous ligands which might act like sigma or phencyclidine drugs. PMID- 2888663 TI - Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase. AB - Organic nitrates develop their vasodilating potency by stimulating the enzyme guanylate cyclase. There are still several theories concerning the molecular mechanism of enzyme activation, the most likely of which sees nitric oxide (NO.) as the true modulator of the soluble guanylate cyclase. We therefore examined the release of nitric oxide from organic nitrates by means of a difference spectrophotometric method and found that our results correlated well with the extent of enzyme activation. The more NO. was liberated from the compounds in question, the higher was the enzyme activation observed. When the examined nitrates were used in a concentration which caused a half-maximal enzyme stimulation, the result was a NO. liberation of striking uniformity. This correlation also applied to SIN-1 for which it has been assumed up to now that the intact molecule itself is able to stimulate the enzyme and not the nitric oxide released from it. We found the reaction between organic nitrates and cysteine to be highly dependent on temperature, while the extent of the observed enhancement increased with the number of nitrate groups per molecule. We also studied the potential effects of certain compounds on non-enzymatic NO. release and found that, in addition to methylene blue, thionine and brilliantcresyl blue, but not ferricyanide, were also effective inhibitors. So it seems likely that both an enzymatic and a non-enzymatic mode of inhibition of enzyme activity does exist. Since oxyhemoglobin is an effective scavenger of nitric oxide, its addition can inhibit enzyme activation by nitrovasodilators. Our results stress the important role of the non-enzymatic liberation of NO. from organic nitrates and related compounds as possible, perhaps even as the principal mode of activation of soluble guanylate cyclase by nitrovasodilators. PMID- 2888664 TI - Ketanserin: systemic and regional hemodynamics in spontaneously hypertensive rats. Role of alpha 1-adrenoceptor blockade. AB - The systemic and regional hemodynamic effects of ketanserin were investigated in spontaneously hypertensive rats (SHRs) using either the pulsed Doppler or the microsphere technique. In addition, the contribution of ketanserin alpha 1 adrenoceptor blocking properties to these hemodynamic effects was assessed. Ketanserin, directly after infusion or secondarily after bolus injection, induced dose-dependent decreases in blood pressure and regional vascular resistances. Peripheral vasodilatation was not homogeneous, affecting in a decreasing rank order: muscle = spleen greater than brain = kidney = total peripheral resistance = liver greater than mesentery = skin. Cardiac output and hindlimb blood flow increased, renal blood flow was maintained whereas mesenteric blood flow was decreased. Prazosin pretreatment, followed by PGF 2 alpha infusion in order to restore initial vascular tone, reduced the ketanserin-induced decrease in blood pressure (by about 70%) and abolished the drug-induced reductions in regional vascular resistances, indicating that these effects in SHRs were mostly due to the alpha 1-adrenoceptor blocking properties of the drug. PMID- 2888665 TI - Relative potencies of neurokinins in guinea pig trachea and human bronchus. AB - The three endogenous neurokinins, substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), as well as NKA-(4-10), carbachol, acetylcholine and histamine, were tested in guinea pig tracheae and human bronchi in order to compare the activities of peptides and non-peptide agents and to characterize the neurokinin receptors by means of agonists. Neurokinin A and NKA-(4-10) were potent stimulants of the two preparations: pD2 values for NKA-(4-10) averaged 8.62 in the guinea pig trachea and 7.50 in the human bronchus. The rank order of potency of neurokinins was NKA-(4-10) greater than NKA greater than SP greater than NKB in the human bronchus and NKA-(4-10) greater than NKA greater than NKB greater than SP in the guinea pig trachea. SP was 2-3 orders of magnitude less active than NKA and appears to be a partial agonist. NKB is inactive on the human bronchus. Compared to non-peptide agents, NKA had an affinity 2-3 orders of magnitude greater than acetylcholine and histamine but produced only 75-80% of the maximal effect of acetylcholine. The present results indicate that neurokinins contract the human bronchus by activating a NK-A receptor type which is more sensitive to NKA than to SP and is insensitive to NKB. The guinea pig trachea appears to be a complex preparation containing not only NK-A but also other neurokinin receptors. PMID- 2888666 TI - Further pharmacological characterization of a D-2-like dopamine receptor on growth hormone producing cells in Lymnaea stagnalis. AB - A preliminary study has revealed that a mammalian D-2-like dopamine (DA) receptor mediates hyperpolarization of the neuroendocrine growth hormone-producing cells (GHCs) in the snail Lymnaea stagnalis. An extensive pharmacological characterization of this receptor was performed in the present study. Several mammalian D-2 receptor agonists (e.g. aminotetralins) and antagonists (e.g.(-) sulpiride) showed agonistic and antagonistic effects, respectively. However, some selective D-2 receptor agonists (e.g. N 0437) and antagonists (e.g. domperidone) failed to show agonistic or antagonistic effects, respectively. It is concluded that the dopamine receptor mediating hyperpolarization of the GHCs displays, besides some similarities, several differences from the mammalian D-2 receptor. PMID- 2888667 TI - Phencyclidine-induced head-weaving observed in mice after ritanserin treatment. AB - Ritanserin (0.125, 0.25, 0.5, 1.0 and 2.0 mg/kg s.c.), a selective serotonin (5 HT2) receptor antagonist, produced a dose-dependent inhibition of the head-twitch response induced in mice by phencyclidine (PCP) and 5-methoxy-N,N dimethyltryptamine (5-MeODMT). In contrast, ritanserin, dose dependently increased PCP- and 5-MeODMT-induced head-weaving. There was a significant inverse relationship between head-twitch and head-weaving responses. Pretreatment with p chlorophenylalanine (PCPA, 300 mg/kg i.p.), a serotonin synthesis inhibitor, attenuated the head-weaving induced by the combination of PCP (12.5 mg/kg i.p.) and ritanserin but PCPA did not alter the 5-MeODMT-induced head-weaving. These results indicate that PCP induces head-weaving by interacting with a 5-HT receptor (possibly of the 5-HT1 subtype) indirectly after 5-HT release and induces head-twitch by interacting with 5-HT2 receptors directly. PMID- 2888668 TI - Opposing central autonomic actions of alpha 1- and alpha 2-adrenoceptor antagonists on oculomotor tone. AB - Electrical stimulation of the afferent sciatic nerve produces reflex mydriasis in anesthetized rats. The alpha 2-antagonist idazoxan (10-100 micrograms/kg i.v.) inhibited this reflex in a dose-dependent fashion. In contrast, the alpha 1 antagonist prazosin (30-300 micrograms/kg i.v.), produced a dose-related enhancement of the reflex. Single dose administration of the alpha 2-antagonists yohimbine (3.0 mg/kg i.v.), rauwolscine (3.0 mg/kg i.v.) and idazoxan (1.0 mg/kg) also blocked the reflex, whereas the alpha 1-antagonists phenoxybenzamine (3.0 mg/kg i.v.), corynanthine (1.0 mg/kg i.v.) and prazosin (1.0 mg/kg i.v.) potentiated this response. These studies demonstrate that alpha 2-antagonists block and alpha 1-adrenoceptor antagonists potentiate alpha 2-adrenoceptor mediated inhibition of oculomotor tone. PMID- 2888669 TI - Effect of calcium agonists and antagonists on cerebellar granule cells. AB - In cerebellar cultures, comprising predominantly granule neurones, dihydropyridine (DHP) Ca2+ agonists were potent stimulators of voltage-sensitive 45Ca2+ uptake. Their effect was maximal in partially depolarized cells; at 15 mM K+e half maximal stimulation occurred at about 5 X 10(-8) M BAY K 8644 and 10(-7) M (+)-(S)-202791. Organic Ca2+ antagonists were effective inhibitors of voltage sensitive calcium entry into granule cells: the order of potency in blocking uptake induced by sub-maximal concentration of K+ and BAY K 8644 was nifedipine greater than (-)-202791 greater than D600. BAY K 8644 also stimulated the release of glutamate, the transmitter of the granule cells, from depolarized cells. Granule cells are therefore a class of neurones whose responsiveness to organic Ca2+ effectors is similar to that of cardiac and smooth muscle. The discrepant findings on the effect of calcium effectors in various preparations of nervous tissues may thus reflect a differential distribution of voltage-sensitive Ca2+ channels in different neuronal cell types. PMID- 2888670 TI - Two populations of neurotensin binding sites in murine brain: discrimination by the antihistamine levocabastine reveals markedly different radioautographic distribution. AB - Monoiodo-[125I-Tyr3]neurotensin (NT) bound to a high affinity, low capacity binding component and a lower affinity, high capacity component in rat brain synaptic membranes. The antihistamine H1 agent levocabastine, which bears no structural relationship to NT, selectively and totally inhibited NT binding to its low affinity binding sites. The IC50 for levocabastine was 7 nM. Lowering the temperature of the binding assay from 25 to 4 degrees C markedly reduced the affinity of the high affinity NT binding site but did not affect the ability of levocabastine to discriminate between high and low affinity NT binding sites in rat brain membranes and tissue sections. Radioautographic studies of [125I Tyr3]NT binding to rat brain tissue sections in the absence and presence of levocabastine revealed markedly different regional distributions of the two NT binding components. The levocabastine-sensitive NT binding site was present in membranes from rat and mouse brain but absent from rabbit brain membranes and from human brain tissue sections. It was also absent from mouse neuroblastoma N1E115 and human colonic adenocarcinoma HT29 cell membranes, two cell lines which have previously been shown to possess NT receptors functionally coupled to intracellular second messenger-generating systems. These findings are discussed in the light of the known properties of the high and low affinity NT binding sites in rat brain. PMID- 2888671 TI - Supersensitivity of d-amphetamine-induced hyperthermia in rats following continuous treatment with neuroleptics. AB - Following short term treatments with the neuroleptic drugs haloperidol, chlorpromazine and oxypertine, there was an increase in the sensitivity of rats to the hyperthermic effects of d-amphetamine. There was no significant difference in the body temperature of control and neuroleptic-treated rats prior to challenge with d-amphetamine. No change in the maximal hyperthermic response was observed. It is possible that these responses may be related to the neuroleptic malignant syndrome occasionally observed in human patients following short term neuroleptic treatments. PMID- 2888672 TI - Fibroblasts modulate expression of Thy-1 on the surface of skeletal myoblasts. AB - Thy-1 antigen is a well-characterized cell-surface glycoprotein known to be variably expressed in many different tissues, including lymphocytes, brain, and muscle. Its function remains unknown. In skeletal muscle, both in vivo and in vitro, the antigen has been reported on immature but not on adult tissue, and its disappearance corresponds roughly to the time of myoblast fusion. Using monoclonal H36 antibody to identify myoblasts unambiguously, we demonstrate here that Thy-1 is expressed only on a small (less than 1%) fraction of rat skeletal muscle myoblasts in heterogeneous primary cultures, but the number of myoblasts that express Thy-1 rises to a steady level of about 70% when fibroblasts are removed from secondary cultures. Restitution of fibroblasts or growth of purified myoblasts in medium conditioned by fibroblasts greatly suppresses this increase in myoblast Thy-1 expression. Thus an interaction between fibroblasts and myoblasts, mediated by a soluble nondialyzable molecule, modulates expression of Thy-1 on the myoblast outer membrane. PMID- 2888673 TI - Glutathione metabolism in normal and cystinotic fibroblasts. AB - Intracellular concentrations of glutathione and activities of the enzymes gamma glutamylcysteine synthetase, glutathione synthetase, and gamma-glutamyl transpeptidase were measured in confluent cultured human fibroblasts cell lines from 14 normal cell lines and four cystinotic cell lines. gamma-Glutamyl transpeptidase had a wide range of variability while the glutathione synthetic enzymes, gamma-glutamylcysteine synthetase and glutathione synthetase, had narrower variations and also exhibited no apparent relationship to glutathione content. No differences in the activities of these enzymes were found between normal and cystinotic cells in confluent cell cultures. The activities of the above enzymes and the cell number and content of glutathione, cystine, DNA, and total protein in two normal and two cystinotic fibroblast cell lines were measured during growth. The following growth-dependency patterns were observed: (1) gamma-glutamylcysteine synthetase activity increased markedly in lag and early log phases in both normal and cystinotic cells and decreased rapidly to low confluent levels thereafter. (2) gamma-Glutamyl transpeptidase showed the same wide range of activity noted at confluency but activities decreased in the log phase of growth, a pattern also seen in cystinotic cells. (3) Glutathione synthetase activity remained relatively constant during growth of normal cells but exhibited a peak of activity during lag and early growth of cystinotic cells. (4) Comparative glutathione levels of normal and cystinotic cells were not significantly different and exhibited similar fluctuations with time. (5) The cystine content of normal and cystinotic cells unexpectedly rose to high levels in the lag phase, then decreased to 0.1 nmol 1/2 cystine/mg protein in normal cells and to 0.3 to 1.2 nmol 1/2 cystine/mg protein in cystinotic cells during the log phase. As confluency was approached, normal cell cystine remained at low levels while cystinotic cell cystine rose to characteristically high levels of 50 to 100-fold greater than normal cells at late confluency. These studies extend our understanding of the regulation of glutathione and cystine content in cultured fibroblasts and suggest that glutathione content is closely controlled throughout the cell cycle in the face of varying activities of its anabolic and catabolic enzymes. PMID- 2888674 TI - Differential expression and modulation of Thy-1 on myoblast clones. AB - In the preceding paper [J. S. Schweitzer, M. A. Dichter, and S. J. Kaufman, 1987, Exp. Cell Res. 172, 1] we demonstrated that expression of Thy-1 antigen by rat skeletal muscle myoblasts in culture is modulated by fibroblasts. Growth of myoblasts with myofibroblasts, or in medium in which fibroblasts have been grown, causes a sharp reduction in the percentage of myoblasts that express Thy-1 antigen on their membrane. In this paper we demonstrate that there are two populations of myoblasts that can be distinguished by their capacity to respond to the Thy-1-modulating factor (TMF). The majority of Thy-1-positive or -negative myoblasts grown at clonal densities are responsive to TMF. A second myoblast clonal type is Thy-1 positive and fuses to form contractile myotubes, but is insensitive to TMF and has a more fibroblast-like morphology. These clonal phenotypes are stable upon passage in vitro and may represent distinct subsets of the myogenic lineage. PMID- 2888675 TI - Transforming growth factor type beta can act as a potent competence factor for AKR-2B cells. AB - Transforming growth factor type beta (TGF beta) is a pleiotropic regulator of cell growth with specific high-affinity cell-surface receptors on a large number of cells; its mechanism of action, however, is poorly defined. In this report, we utilized the mouse fibroblast line AKR-2B to explore the question of the temporal requirements during the cell cycle in regard to both the growth inhibitory and the growth stimulatory action of TGF beta. The results indicate that AKR-2B cells are most sensitive to the inhibitory action of TGF beta during early to mid-G1. In addition, TGF beta need be present only briefly (as little as 1 min) in order to exert its inhibitory effect on EGF-induced DNA synthesis. Likewise, the stimulatory effect of TGF beta in the absence of EGF requires only an equally brief exposure to TGF beta. Use of homogeneous 125I-labeled TGF beta in a cell binding assay demonstrates that TGF beta bound to cell-surface receptors can readily exchange into the culture medium T1/2 = 120 min), helping to rule out the possibility that persistent receptor-bound TGF beta is the source of a continuous stimulus. The data indicate that TGF beta exposure induces a stable state in the cell (T1/2 = 20 h) similar to but distinct from the state of "competence" induced by platelet-derived growth factor (PDGF). PMID- 2888676 TI - Metabolism of glutamine and glutamate in monkey lens. AB - In rat and bovine lenses, the primary source of intracellular glutamate has been shown to be glutamine transported from the surrounding fluids, whereas extracellular glutamate is less readily utilized. For comparison, glutamine and glutamate metabolism were studied in a primate. Fresh, intact lenses from Rhesus monkeys (Macaca mulatta) were incubated in balanced salt medium containing [15N]glutamate (Group A) or amino-labeled [15N]glutamine (Group B). In contrast to other species, the monkey lenses metabolized the glutamate more rapidly than the glutamine, although glutamine entered the lenses more rapidly than glutamate. Formation of labeled aspartate, alanine, proline, and serine was more rapid in Group A than in Group B, but labeling of the lenticular glutamate + glutamine pool was more rapid in Group B. This indicated that, in monkey lenses, deamidation of glutamine is sufficiently slow to limit the entry of glutamine into pathways requiring or preferring glutamate. The difference in rates of deamidation of glutamine in intact monkey lenses and rat lenses was confirmed by measuring the rate of ammonia release by lenses incubated with glutamine. PMID- 2888677 TI - Correlation between histopathological, clinical and biochemical parameters in S antigen-induced experimental autoimmune uveitis in guinea-pigs. AB - Footpad immunization with purified bovine retinal S-antigen in complete Freund's adjuvant was used to induce experimental allergic uveitis in 32 guinea-pigs. Thirteen animals immunized only with complete Freund's adjuvant were used as controls. Ninety-three point seven per cent of the animals immunized with S antigen developed clinical experimental allergic uveitis while none of the controls had any clinical manifestation of uveitis. Histopathological analysis in the experimental group revealed mono- and polymorphonuclear cell infiltration in the choroid, ciliary body and iris. Simultaneous disruption of the outer segment of photoreceptor cell layer was also noticed. For the anterior segment of the eye there was a strong correlation between the histopathological grading and the clinical grading. For the posterior segment this correlation was, however, poor. Histopathological changes in the eye were correlated with the clinical grading and biochemical parameters (phospholipase A2, prostaglandin E2, leukotriene C4, proteins and myeloperoxidase) measured from aqueous humour, serum samples and ciliary body-iris homogenate. Protein and phospholipase A2 levels in the aqueous humour correlated well with the histological grading of the anterior segment of the eye. The myeloperoxidase activity, measured from ciliary body-iris homogenate, also correlated with the inflammatory cell infiltration in the anterior segment. Leukotriene C4 and prostaglandin E2 levels in aqueous humour did not correlate with the histopathological, or with the clinical grading, although elevated mean values were recorded in eyes having uveitis. Gamma glutamyl transpeptidase, measured in the serum, had a poor correlation with the histological grading for the anterior segment. All other parameters, measured in serum, did not correlate with the histopathological or the clinical grading. Histopathological changes in the anterior uvea are thus reflected by elevated protein and phospholipase A2 levels in aqueous humour as well as by myeloperoxidase activity in ciliary body-iris homogenate. PMID- 2888678 TI - Interplexiform cells in macaque monkey retina. AB - The presence of interplexiform cells in primate retina has been disputed, with the dopaminergic interplexiform cell in the New World monkey being the most fully understood. We have examined interplexiform cells in the Old World monkey using immunocytochemistry with the peroxidase-antiperoxidase method of visualization. In several species of macaque retina, two types of interplexiform cells are found. One stains with antisera to tyrosine hydroxylase, a biosynthetic enzyme for dopamine, and the other stains with antisera to gamma aminobutyric acid (GABA). The cell bodies of these two populations of interplexiform cells are located among the amacrine cells in the inner nuclear layer, and they send processes into both the inner and outer plexiform layers. GABA-positive interplexiform processes to the outer plexiform layer arise from the cell body while tyrosine hydroxylase-positive interplexiform processes most often originate from the heavily tyrosine hydroxylase-stained sublamina one of the inner plexiform layer. Cell-body diameter measurements and morphology suggest that these are different neuronal populations. PMID- 2888679 TI - Pharmacological analysis of vasoconstriction of isolated canine ophthalmic and ciliary arteries to alpha-adrenoceptor agonists. AB - Effects of five alpha-adrenoceptor agonists were investigated on the canine internal, external ophthalmic and ciliary arteries by the use of several kinds of antagonists. These arteries were isolated with the optic nerve and perfused with Tyrode solution under a constant flow rate at 37 degrees C. Control perfusion pressure was within 40-80 mmHg. Each drug solution except sodium nitroprusside (SNP) was administered by a microinjector into the endothelial side of the artery through a cannulated tubing, and SNP was administered by being dissolved into the perfusion solution. The response was obtained as changes in perfusion pressure. Results were as follows: (1) epinephrine (EPI), norepinephrine (NE), phenylephrine (PHE), and KCl induced a marked vasoconstriction in these arteries, although xylazine (XYL) and clonidine (CLO) did not produce any significant change; (2) bunazosin, a potent alpha-1 adrenoceptor blocker, antagonized the effects of NE and PHE in a dose-related manner, and did not affect the responses to KCl; (3) diltiazem reduced the KCl-induced vasoconstriction in a dose-related manner, and it did not significantly influence the vascular responses to NE; (4) SNP reduced the NE-induced vasoconstriction but the KCl-induced vasoconstriction was only suppressed by a large dose of SNP. From these results, it is suggested that; (1) these arteries contain alpha-1 but not alpha-2 adrenoceptors; (2) NE induced vasoconstriction is independent of the Ca2+ inward current but probably involves intracellular Ca2+ ion movement; (3) SNP may influence intracellular Ca2+ movement in these arteries. PMID- 2888680 TI - In vitro maintenance of hemopoietic stem cells with lymphoid and myeloid repopulating ability by a cloned murine adherent bone marrow cell line. AB - Colonies containing blast cells (greater than 95%) have been characterized in 14 day cultures of normal murine bone marrow or spleen cells, stimulated by an adherent bone marrow cell line, B.Ad. These blast cell colonies occurred at a frequency of 1-2 per 2.5 X 10(4) bone marrow or 2.5 X 10(5) spleen cells and contained from 0.7 to 14.7 X 10(4) cells. Assay of individual blast cell colonies showed that they contained day 8 and day 13 colony-forming units-spleen (CFU-S) and from 11 to 10,434 in vitro CFC. Chromosomally marked blast colony cells were transplanted into lethally irradiated recipients and shown to produce both myeloid and lymphoid progeny in the recipients' bone marrow, spleen, mesenteric lymph node, and thymus. PMID- 2888681 TI - Localization of glutamate, glutaminase, aspartate and aspartate aminotransferase in the rat midbrain periaqueductal gray. AB - Glutamate and aspartate are putative excitatory neurotransmitters in the central nervous system. The present study utilized novel monoclonal antibodies against fixative-modified glutamate and aspartate and polyclonal antisera against the amino acid synthesizing enzymes, glutaminase and aspartate aminotransferase, to analyze the distribution of these amino acids in the rodent midbrain periaqueductal gray. Glutamate-, aspartate-, glutaminase- and aspartate aminotransferase-like immunoreactive neurons, fibers and processes are present throughout the rostrocaudal length of the periaqueductal gray. Glutamate- and glutaminase-like immunoreactive neurons displayed a similar homogeneous pattern of distribution, being localized predominantly to the lateral and dorsal subdivisions of the periaqueductal gray. Co-localization experiments suggest that glutamate and glutaminase are in fact co-contained within the same PAG neurons. Aspartate aminotransferase-like immunoreactive neurons were distributed in a pattern similar to glutamate and glutaminase with the exception that fewer cells were stained in the dorsocaudal and the rostral third of the PAG. Aspartate-like immunoreactive neurons were less numerous than glutamate-like immunoreactive cells and were located in the lateral aspect of the PAG. These results demonstrate a specific and distinct distribution of glutamate and aspartate immunoreactive neurons and support recent data suggesting that glutamate and aspartate serve as excitatory neurotransmitters in the PAG. PMID- 2888682 TI - Early visual deafferentation of the cortex results in an asymmetry of somatostatin labelled cells. AB - Biologically active peptides are distributed widely throughout the nervous system. The distribution of each is not random, but follows a relatively specific pattern. Although the time course of development of a number of peptides has been traced, the factors which determine their distribution and function remain unknown. In this study we report changes which occur preferentially in the distribution of one peptide, somatostatin, in the visual cortex of the rat, as a consequence of early unilateral eye removal. Because the uncrossed retinal projection is so small in the rodent, this manipulation substantially reduces the visual innervation of the cortex ipsilateral to the remaining eye, and is correlated here with an asymmetry in the number of somatostatin positive cells. PMID- 2888683 TI - Trichinella spiralis: genetic evidence for synanthropic subspecies in sylvatic hosts. AB - Isolates of the nematode genus Trichinella from sylvatic hosts differ in their potential to reproduce in domestic swine. The structure of the genomic DNA from 13 sylvatic isolates from North America and 5 pig isolates, 4 from North America and 1 from Asia, was examined and correlated with the infectivity of the isolate for domestic pigs. DNA restriction fragment length differences, identified by ethidium bromide staining and by hybridization with 32P-labeled ribosomal RNA, served as molecular markers to classify each isolate. All 5 pig isolates and 8 of 13 sylvatic isolates had a high infectivity and reproductive capacity in pigs. All isolates that were highly infectious for pigs regardless of host origin had similar DNA characteristics and were classified operationally as T. spiralis spiralis (pig) and those of the second group as T. spiralis ssp. A DNA clone of repetitive DNA from T. s. spiralis, pBP2, was selected from a library of genomic DNA in plasmid pUC8. When used as a probe, pBP2 hybridized only to the DNA of T. s. spiralis isolates, thus making it a useful diagnostic reagent to predict whether new isolates are highly infectious for pigs (i.e., T. s. spiralis). These results show that T. s. spiralis occurs in wild mammals and this should be considered a serious obstacle to efforts to eradicate trichinellosis from domestic swine. PMID- 2888685 TI - The quantitative significance of asbestos fibres in the ambient air. PMID- 2888684 TI - Neural control of the circulatory system of Aplysia. PMID- 2888686 TI - Influence of level of dietary protein on tryptophan-induced promotional activity in induction of gamma-glutamyl transpeptidase-positive foci of rat liver. AB - The influence of varying the dietary protein content on the emergence of gamma glutamyl transpeptidase (GGT)-positive foci in the livers of male rats fed elevated (2%) L-tryptophan (TRP) after being exposed to a hepatocarcinogen was investigated. Subtotal hepatectomies were performed, and 18 hr later the rats were treated with diethylnitrosamine (30 mg/kg). Ten days later four dietary groups were followed for 10 weeks: (1) control diet containing 21% protein (C); (2) control diet containing 5.3% protein (C-LP); (3) C + TRP; and (4) C-LP + TRP. Rats fed the C-LP diet developed heavier livers but fewer and smaller GGT + foci than did rats fed the C diet. Rats fed elevated TRP diets (C + TRP and C-LP + TRP) developed more and larger GGT + foci than did rats fed the regular control diets (C and C-LP), indicating that the promotional effect of elevated dietary TRP was similar at the two levels of dietary protein. PMID- 2888687 TI - Adherence of bacteria to cardiac valve prostheses. AB - The adherence of bacterial cells to valvular prostheses has been studied. Bacteria were selected on the basis of their surface features (fimbriae, hydrophobicity and specific receptors). It was found that only strains having fimbriae and high cell surface hydrophobicity adhered to bioprostheses, while they did not adhere to metallic prostheses to any significant extent. Adherence to bioprostheses depended on the exposure time and it was affected by the saline concentration of the suspension medium. Furthermore, different bacterial binding capacity was observed for bioprostheses from different companies. PMID- 2888688 TI - Clinical and epidemiological aspects of hemorrhagic fever with renal syndrome (HFRS) in Greece. AB - Twenty-three cases of hemorrhagic fever with renal syndrome were serologically diagnosed in rural populations of Greece between 1982 and 1985. The clinical picture of the disease was severe, (3 deaths recorded among 23 cases) and more closely resembled Korean hemorrhagic fever than nephropathia epidemica. Examination of patients' sera by indirect immunofluorescence (IFA) assays and plaque reduction neutralization (PRNT) tests using Hantaan 76-118, Puumala, and Seoul (Urban rat-associated Hantaan-like) viruses, suggested that the virus existing in Greece is either prototype Hantaan virus or a distinct virus which is closely related to Hantaan. Small mammal survey results suggest that Apodemus flavicollis may be the host of this virus. Serosurvey results of 2,653 blood samples taken from apparently healthy residents (farmers, shepherds, and woodcutters) from 22 of 54 counties in Greece, showed the percentage of seropositives to be 4%, with a range from 0 to 14%. Fifteen of 22 counties were characterized as endemic areas of the virus due to the presence of seropositive individuals. In 6 of the 15 endemic areas, overt human disease was serologically diagnosed. PMID- 2888689 TI - [Synthesis and antiparasitic activity of new nitro-5-imidazole derivatives]. AB - Syntheses are given for derivatives of the type: 2-amino-1-[(1-methyl-5-nitro-2 imidazolyl) methyleneimino] imidazole, of new hydrazones of 1-methyl-5 nitroimidazole-2-carboxaldehyde and also for semicarbazones and a hydrazone of 1 methyl-5-nitro-2-(4-formyl-styryl)imidazole. PMID- 2888690 TI - On the rate of F1-ATPase turnover during ATP hydrolysis by the single catalytic site. Evidence that hydrolysis with a slow rate of product release does not occur at the alternating active site. AB - Under conditions of molar excess of enzyme, isolated F1-ATPase from beef heart mitochondria catalyses ATP hydrolysis biphasically. The rate constants for product release are approximately 10(-1) and 10(-4)-10(-3) s-1, respectively. The slow phase of ATP hydrolysis is insensitive to EDTA. [gamma-32P]ATP splitting in the slow phase cannot be chased from the enzyme during several catalytic turnovers. It follows from these results that the slow single-site hydrolysis of ATP (kcat approximately 10(-4) s-1), initially observed by Grubmeyer et al. [(1982) J. Biol. Chem. 257, 12092-12100], is not carried out by the normal catalytic site. In contrast, the phase of rapid ATP hydrolysis (kcat approximately 10(-1) s-1) is completely prevented by EDTA and is believed to be the normal function of the normal catalytic site of F1-ATPase. PMID- 2888691 TI - Subjective assessment of the effect of cataract surgery and a review of long term aims. Oxford Cataract Treatment and Evaluation Team (O.C.T.E.T.). AB - A questionnaire designed to test subjective assessment of functional improvement was given to 327 patients in a randomised controlled trial one year after operation for cataract. Approximately one-third of the patients had a contact lens fitted after intracapsular extraction (I/C) and two-thirds had intraocular implants after both I/C and extracapsular extraction. The great majority of patients admitted to functional improvement irrespective of treatment mode. A review of objective data from the study suggests that the beneficial effects of surgery are likely to be long lasting. PMID- 2888692 TI - Multi-centre double-blind comparison of terfenadine once daily versus twice daily in patients with hay fever. AB - This double-blind, randomized multi-centre study was designed to compare efficacy and tolerability of 120 mg terfenadine taken once daily (in the morning) with the established regimen of 60 mg terfenadine taken twice daily in the treatment of seasonal rhinitis. Two comparable groups, a total of 191 hay fever patients, were treated for 1 week. Symptom severity was assessed by the investigators before and at the end of the treatment (visual analogue scale), and daily by the patient (four-point rating scale). All symptoms improved to a similar degree in both groups. Differences between the two groups were not statistically significant, except for nasal symptoms in three cases as assessed by the visual analogue scale in one centre (better relief in the group given 120 mg terfenadine once daily). Tolerability was good and similar in both groups. The data presented show that in the treatment of hay fever 120 mg terfenadine given once daily is an effective, convenient and well tolerated alternative to the regimen of 60 mg terfenadine given twice daily. PMID- 2888693 TI - Effect of H2-receptor blockade on gastric mucus composition. A comparative study with ranitidine and famotidine. AB - The effects on gastric mucus by two different H2-receptor antagonists, famotidine and ranitidine, have been investigated in 20 patients with duodenal ulcer. Before and after 4 weeks' treatment with either drug the quality of mucus secretion was assessed by means of a 'mucoprotective index'. A significant (P less than 0.01) decrease in the values of this index was observed in famotidine-treated subjects, whereas no changes were detected in those given ranitidine. The findings of this study with famotidine are in keeping with the results previously reported with cimetidine using the same method. It is suggested that blockade of gastric H2 receptors alters the composition of gastric mucus in man. This effect is not shared by ranitidine. PMID- 2888694 TI - A comparison of the effects of bromocriptine and somatostatin on growth hormone gene expression in the rat anterior pituitary gland in vitro. AB - The effects of the dopamine agonist bromocriptine (BCR) have been compared with those of somatostatin (SS) on growth hormone (GH) synthesis and secretion by rat anterior pituitary cells in vitro. Both BCR and SS produced a dose-related reduction in GH release. Cytoplasmic GH mRNA levels were unchanged by BCR treatment and this finding was associated with an increase in total intracellular GH content. The reduction in GH release seen following SS treatment was accompanied by a fall in cytoplasmic GH mRNA levels and no significant change in intracellular GH content. These results suggest that the effects of BCR are predominantly on GH release mechanisms, whereas SS appears not only to regulate hormone release but also to regulate GH gene expression at a pre-translational level. PMID- 2888695 TI - Loss of early phase of insulin release in humans impairs glucose tolerance and blunts thermic effect of glucose. AB - Loss of the early phase of insulin release has been documented in both type I (insulin-dependent) and type II (non-insulin-dependent) diabetes; however, the physiological importance of this loss is unsettled. We created a model of loss of the early phase of insulin release in normal volunteers. Somatostatin (SRIF) was briefly infused (from -5 to 15 min) during intravenous (IVGTT) and oral (OGTT) glucose tolerance tests. The thermic response to oral glucose was determined under these conditions by indirect calorimetry. Early insulin release was totally blocked during IVGTT and OGTT by SRIF infusion. During the IVGTT, glucose tolerance was deteriorated in association with loss of the early phase of insulin release as indicated by a decrease in the K value (control 1.9 +/- 0.36 vs. SRIF 1.1 +/- 0.27, P less than .001). Higher plasma glucose concentrations were observed during SRIF tests in the OGTT at 60, 90, 120, 150, and 180 min; total glycemic excursion was larger during the SRIF test (9473 +/- 3089 mg X dl-1 X 5 h 1) when compared with the control condition (6583 +/- 2329 mg X dl-1 X 5 h-1). During the OGTT the total amount of glucose oxidized (control 56 +/- 4.2 vs. SRIF 55 +/- 3.4 g/5 h) was similar in both conditions, suggesting that nonoxidative pathways of glucose disposal were responsible for the deterioration in glucose tolerance. Surprisingly, we found that glucose-induced thermogenesis was reduced in association with loss of the early phase of insulin release (control 102 +/- 21.3 vs. SRIF 72 +/- 27.8 J/5 h, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888696 TI - Calculated pattern of intraportal insulin appearance without independent assessment of C-peptide kinetics. AB - Prehepatic beta-cell insulin release can be calculated with C-peptide measurements, but this requires independent determination of kinetics of C peptide disappearance from plasma. We introduce an approach by which a prehepatic insulin release pattern is calculated from plasma insulin and C-peptide, without separate C-peptide kinetic analysis. Human insulin and C-peptide were infused intraportally into conscious dogs (n = 11) at equimolar rates; endogenous insulin and C-peptide release were suppressed with somatostatin (0.8 micrograms . kg-1 . min-1). Insulin and C-peptide were infused at basal and equimolar rates (range 19 72 pmol/min in dogs), and the infusions were slowly increased, in stepwise fashion, to a maximum at 60 min (range 152-613 pmol/min) and subsequently renormalized at either 85 (n = 6) or 195 (n = 5) min. Plasma insulin and C peptide measurements were described simultaneously by a composite model of insulin and C-peptide plasma kinetics, with the molar intraportal appearance rate due to the infusion R(t) as an unknown input for both insulin and C-peptide catabolism. The model assumes one-compartment disappearance kinetics for both peptides. Fitting the model to the measured insulin and C-peptide data, we were able to compute the insulin-appearance pattern accurately for every experiment; calculated and actual secretion rates were highly correlated (r = .93-.97) and had very similar temporal patterns. Also calculated were the fractional disappearance rates for human insulin (t1/2 = 6.9 min) and C-peptide (t1/2 = 14 min) in the dog, as well as the C-peptide distribution volume (12.3 +/- 0.5% body wt).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888697 TI - Effect of atropine and somatostatin on bombesin-stimulated plasma immunoreactive trypsin release in man. AB - This study was undertaken to determine the effect of atropine and somatostatin, two inhibitors of intraduodenal pancreatic enzyme secretion, on bombesin stimulated release of plasma immunoreactive trypsin in 6 healthy volunteers. Infusion of 5 ng/kg.min bombesin during 30 min induced significant increases in plasma trypsin from 206 +/- 20 to 334 +/- 44 ng/ml (p less than 0.01). Atropine (15 ng/kg as i.v. bolus followed by 5 ng/kg.h) had no influence on the bombesin stimulated increase in plasma immunoreactive trypsin (207 +/- 20 to 326 +/- 54 ng/ml). Somatostatin (125 micrograms as i.v. bolus followed by 125 micrograms/h) also failed to inhibit the plasma trypsin response to bombesin (207 +/- 18 to 663 +/- 166 ng/ml). These results point to major differences in the regulation of plasma and intraduodenal trypsin secretion. PMID- 2888698 TI - Linkage analysis of the human insulin receptor gene and maturity onset diabetes of the young. AB - The cloning of the insulin receptor cDNA has permitted the definition of restriction fragment length polymorphisms at that locus. These polymorphisms were used to study the role of the insulin receptor in four pedigrees with maturity onset diabetes of the young through linkage analyses. When each pedigree was individually analysed, no linkage was demonstrated in the two larger pedigrees, implying that an insulin receptor defect was not responsible for the predisposition to diabetes in these pedigrees. One of these pedigrees was known to be hypoinsulinaemic, while insulin levels were unavailable in the second pedigree. In the two smaller pedigrees, however, a single haplotype cosegregated with diabetes. One of these pedigrees is known to be hyperinsulinaemic. The small size of the pedigrees which demonstrated cosegregation precluded statistical proof of linkage. Nonetheless, the presence of an uncommon insertional polymorphism which cosegregated with diabetes in both pedigrees was improbable and suggested that this insertion could be responsible for diabetes in these families. This study thus may be additional evidence for heterogeneity in maturity onset diabetes of the young. For the two larger pedigrees, the insulin gene and HLA region have already been eliminated as genetic markers. This study provides data which eliminate a third candidate gene in these two pedigrees. PMID- 2888699 TI - A species comparison of the toxicity of nabilone, a new synthetic cannabinoid. AB - Acute, subchronic, and chronic studies were conducted in various species to evaluate and compare the toxicity of nabilone, a new synthetic 9-ketocannabinoid that is orally effective for the treatment of nausea and vomiting induced by cancer chemotherapy agents. The oral LD50 in mice and rats for nabilone formulated as a polyvinylpyrrolidone (PVP) codispersion was in excess of 1000 mg/kg. Among nonrodents, rhesus monkeys had a higher tolerance to the CNS depression induced by single oral doses of nabilone-PVP than did dogs. Rats fed dietary mixtures of nabilone-PVP which provided approximate daily nabilone doses of 1 to 93 mg/kg tolerated treatment for 3 months with no deaths. Treatment related changes (at doses greater than or equal to 5 mg/kg) were limited to reduced body temperature, slight-to-moderate decreases in weight gain, and behavioral changes (e.g., hyperactivity, hyperirritability to touch, and hypoactivity). All dogs treated for 3 months with daily oral doses of up to 1.0 mg/kg survived; treatment-related effects were limited to transient episodes of ataxia and anorexia. Nabilone treatment of rats and dogs for 3 months produced no evidence of systemic toxicity in the clinical chemistry, hematology, or pathology parameters examined. Chronic treatment of dogs with daily oral doses of nabilone PVP equal to 0.5, 1.0, or 2.0 mg of nabilone/kg produced cumulative toxicity; by the end of 7 months, 2, 6, and 7 dogs in the respective dose groups had died. In a number of instances, death was preceded by one or more convulsive episodes. In contrast to the dog, the toxic potential of nabilone was minimal in rhesus monkeys treated with nabilone-PVP for 1 year at daily oral nabilone doses of up to 2.0 mg/kg. The enzymatic reduction of the 9-keto group of nabilone to form carbinol metabolites was a major metabolic pathway for nabilone in dogs but not in rhesus monkeys. The carbinols were long-lived metabolites in the plasma of dogs and accumulated in the plasma compartment with time. Furthermore, the carbinol metabolites were found to concentrate in the brain tissues of treated dogs. Although the precise mechanism for this marked species difference in chronic toxicity is not known, the metabolic differences responsible for the presence of the carbinol metabolites at high concentrations in the plasma and brain over time may play a role in the toxicity observed in the dog. PMID- 2888700 TI - [Hypercalcemia and neoplasms]. PMID- 2888701 TI - Comparison of the biochemical changes in the jejunal mucosa of dogs with aerobic and anaerobic bacterial overgrowth. AB - Subcellular biochemical changes in the jejunal mucosa have been compared in dogs with either aerobic or anaerobic bacterial overgrowth to explore relationships between composition of the flora and mucosal damage. Affected animals comprised 17 German shepherd dogs with chronic diarrhea or weight loss, or both. Analysis of duodenal juice demonstrated aerobic overgrowth in 10 cases, most frequently comprising enterococci and Escherichia coli, and obligate anaerobic overgrowth in 7 cases, most frequently including Clostridia spp. Histologic changes were minimal; however, examination of peroral jejunal biopsy specimens by sucrose density gradient centrifugation revealed specific biochemical abnormalities. In the dogs with aerobic overgrowth, there was a selective loss of brush border alkaline phosphatase activity, and gamma-glutamyl transferase activity was increased, whereas activities of disaccharidases and aminopeptidase N were unaltered. In contrast, anaerobic overgrowth was associated with a reduction in brush border density, indicative of a considerable fall in the glycoprotein-to lipid ratio of the brush border membrane, whereas brush border enzyme activities were unaltered. There was a loss of peroxisomal catalase activity in dogs with aerobic overgrowth, and an indication of mitochondrial disruption in dogs with anaerobic overgrowth, but little evidence for damage to other subcellular organelles. These findings demonstrate that aerobic and anaerobic overgrowth may be associated with distinct but different mucosal abnormalities particularly affecting the brush border membrane. PMID- 2888702 TI - Influence of vagal integrity on gastrin and somatostatin release in dogs. AB - Plasma gastrin and somatostatin responses to ingestion of a solid meal, to insulin hypoglycemia, and to intravenous infusion of gastrin-releasing peptide were measured in 4 conscious dogs with and without bilateral cryogenic blockade of the cervical vagus nerves. Vagal cooling to -2 degrees C abolished meal stimulated rises in plasma gastrin and somatostatin. Atropine did not modify the gastrin response to cooling but bethanechol reduced the magnitude of inhibition to 37% +/- 9% without influencing plasma somatostatin. Gastrin-releasing peptide elevated postprandial plasma gastrin during vagal blockade to levels comparable to those with the vagus intact but did not alter the nadir plasma somatostatin response. The plasma gastrin and somatostatin rises associated with insulin hypoglycemia were similarly inhibited by cooling to -2 degrees C. Cooling to 12 degrees C, which selectively blocks vagal inhibitory pathways, had no effect on meal-stimulated gastrin release and partially decreased the plasma gastrin response to insulin hypoglycemia. Thus, gastrin release by food and by insulin hypoglycemia is mediated by a vagal nonmuscarinic excitatory pathway that is independent of changes in circulating plasma somatostatin but may include participation by the candidate neurotransmitter gastrin-releasing peptide. PMID- 2888703 TI - Subsensitivity to beta-adrenoceptor agonists in right atria isolated from footshock-stressed rats. AB - 1. The effects of three daily sessions of inescapable footshock on the sensitivity of rat isolated right atria to the chronotropic effect of norepinephrine, tyramine and soterenol were studied. 2. Inescapable footshock induces subsensitivity to norepinephrine and tyramine. The maximum response to the partial agonist soterenol was reduced. 3. In vitro denervation and addition of cocaine prevented the demonstration of inescapable footshock-induced subsensitivity to norepinephrine. 4. It is concluded that repeated inescapable footshock stress reduces the number of atrial beta 1-adrenoceptors and increases the efficiency of the neuronal reuptake process. PMID- 2888704 TI - Nifedipine vasodilates human forearm arteries and dorsal hand veins constricted by specific alpha-adrenoceptor stimulation. AB - 1. The local dilative effect of the calcium entry blocker nifedipine on forearm arteries and dorsal hand veins has been studied in 27 healthy male volunteers. 2. Nifedipine induced an increase of blood flow by 1190% (P less than 0.001) in the forearm. 3. The construction of the hand veins induced by stimulation of either postsynaptic alpha 1- or alpha 2-adrenoceptors was reduced (P less than 0.001) by nifedipine. 4. The calcium entry blocker nifedipine is a potent dilator of human forearm arteries as well as of dorsal hand veins. PMID- 2888705 TI - Effects of alpha-adrenoceptor stimulation on electrophysiological properties and mechanics in rat papillary muscle. AB - 1. Electrophysiological and inotropic responses to stimulation of alpha adrenoceptors were examined in isolated rat papillary muscles. 2. Stimulation of alpha-adrenoceptors caused two major electrophysiological changes, i.e. prolongation of action potential duration (APD) and hyperpolarization of resting membrane potential. 3. The time course of the inotropic responses to alpha adrenoceptor stimulation was composed of an initial, short-lasting and small positive phase followed by a negative phase and then a second increasing phase. 4. Nifedipine abolished the alpha-adrenoceptor-mediated positive inotropic effect whereas unaffecting the negative inotropic effect, the APD prolongation and the hyperpolarization. 5. In quiescent muscles alpha-adrenoceptor stimulation also produced hyperpolarization, which was blocked by Ba2+. PMID- 2888706 TI - Tissue and plasma distribution of exogenous growth hormone-releasing factor analogue (GRF1-29NH2) after intravenous, subcutaneous and intraperitoneal injection in the rat. AB - 1. The administration of 125I-labelled growth hormone-releasing factor (GRF) analogue 1-29NH2 by intravenous, subcutaneous or intraperitoneal injection to rats leads to rapid (i.v.) or slow (s.c. and i.p.) increases in plasma radioactivity followed by extensive breakdown of the peptide. 2. Tissues possessing GRF-like immunoreactivity such as gastric antrum (but not fundus), duodenum and ileum showed in vitro specific uptake of 125I-GRF probably mediated by vasoactive intestinal peptide (VIP) receptors. 3. Pituitary (the primary target organ for GRF) but neither thyroid nor parathyroid exhibited specific uptake of 125I-GRF. PMID- 2888707 TI - [Cloning of the ADE2 gene of Saccharomyces cerevisiae and localization of the ARS sequence]. AB - Mutational changes in ADE2 result in the accumulation of red pigment in cells, which serves as an indicator for the selection of mutants. This easily detectable phenotype of red-coloured colonies can account for the wide use of ade2 mutants in yeast genetics. ADE2 gene was cloned in a shuttle vector by complementing the ade2 mutation in the yeast. It was shown that the 2.2 kbp HindIII fragment of yeast DNA contains structural sequences of the ADE2 gene as well as the ARS sequence. Deletion analysis of the 5' end of the ADE2 gene showed the ARS sequence to be situated at the distal end of the 1 kbp HindIII fragment. Removal of the ARS sequence does not influence ADE2 gene complementation ability. Transformants containing the ADE2 gene comprised in their plasmids form white colonies. Loss of the plasmids results in colour change of colonies. PMID- 2888708 TI - Y-chromosomal DNA polymorphism in mouse inbred strains. PMID- 2888709 TI - Brain neurotransmitters in aging and dementia: similar changes across diagnostic dementia groups. AB - Reductions of the levels of transmitter substances and of the activities of enzymes involved in their synthesis have been demonstrated in the aging brain. The sensitivity to the aging process varies for different transmitters and brain regions. Dopamine neurons are more age-sensitive than most other neurons investigated. The metabolism of monoaminergic neurotransmitters is enhanced in the aging brain, as evidenced by increased metabolite/neurotransmitter ratios, perhaps to compensate for the loss of transmitter. In various types of dementia, including Alzheimer's disease (AD) and senile dementia of Alzheimer type (SDAT), several neurotransmitter indices are reduced, as compared to age-matched controls. Moreover, a decrease in neurotransmitter metabolites suggests that compensatory mechanisms are insufficient. No correlation could be found between the neurotransmitter changes and the histological changes characteristic of AD (senile plaques and neurofibrillary tangles). Neither could any relationship between multiple infarctions and neurotransmitter indices be detected. Recently observed changes in the lipid composition of the white matter, indicating demyelinization, in the brains of patients with AD/SDAT, emphasize the multifactorial aspects of dementia. Taken together, the data underline the difficulties in drawing clear demarcation lines between normal and pathological aging and between different subgroups of dementia. Despite the obvious difficulties, future therapeutic efforts should aim at substitution for the neurotransmitter deficiencies. Preventive measures have to await the clarification of the mechanisms underlying neural degeneration. Studies of the toxicity of oxygen and of autoxidation products are among the areas of research that may help to shed light on this problem. PMID- 2888710 TI - [Effect of 17 beta-estradiol on dihydro-orotase activity of the liver, kidney and uterus of rats]. PMID- 2888711 TI - Effect of sulphasalazine and its metabolites on the generation of reactive oxygen species. PMID- 2888712 TI - Risk factors for tardive dyskinesia according to primary psychiatric diagnosis. AB - The role of different variables in the development of tardive dyskinesia was examined among patients in two different diagnostic categories. Age and length of hospitalization were associated with development of tardive dyskinesia in the schizophrenic subjects while parkinsonism and alcoholism were related to tardive dyskinesia in the affective disorder patients. Schizophrenic subjects constituted the largest absolute number of tardive dyskinesia patients, but in relative terms they represented the patient population least likely to develop tardive dyskinesia in comparison to affective disorder and organic mental disorder subjects. The clinical implications of these findings are discussed. PMID- 2888713 TI - Establishment and characterization of a diethylnitrosamine-initiated woodchuck hepatocyte cell line. AB - Woodchucks free from woodchuck hepatitis virus were treated with diethylnitrosamine in vivo for 2 months, and then hepatocytes obtained by enzymatic perfusion were cultured with the hepatopromoter phenobarbital. This in vivo-in vitro procedure gave rise to proliferating epithelial cell foci, from one of which the presently described hepatocyte cell line (WLC-3) was established and characterized. WLC-3 cells possess morphological and biochemical features of differentiated hepatocytes, including glucose-6-phosphatase activity and albumin production. Histopathological analysis of the tumor which developed transitorily in nude mouse subcutis after inoculation of the cell line revealed glandular structures comprising cells of hepatocellular-like morphology. This is the first established woodchuck hepatocyte cell line free from woodchuck hepatitis virus and is therefore expected to be useful for studying the mode of gene expression and viral proliferation of woodchuck hepatitis virus and the mechanisms underlying woodchuck hepatitis virus-related hepatocarcinogenesis. PMID- 2888714 TI - Chromosomal abnormalities in non-Hodgkin lymphoma with peripheral T-cell type: effect of HTLV-I infection. AB - Cytogenetic studies were done in lymph node and peripheral leukemic cells from sixteen patients with non-Hodgkin lymphoma with peripheral T-cell type. Ten patients were positive for human T-cell leukemia virus I (HTLV-I) proviral DNA in tumour cells and six were negative. The former group had a higher tendency for leukemic conversion and poorer prognosis than the latter. However, no definite difference on the numerical and structural chromosomal abnormalities between these two groups was found. The most frequent chromosome abnormalities: 14p+, 14q+ and No. 6 abnormalities were detected in both groups. These results may indicate that HTLV-I does not play a specific role in chromosome abnormalities of non-Hodgkin lymphoma with peripheral T-cell type. PMID- 2888715 TI - Peripheral T-cell lymphoma: a clinicopathologic study of 42 cases. AB - We analysed the clinical and pathologic features of 42 patients with immunologically confirmed peripheral T-cell lymphoma. The median age was 60 years and the male to female ratio was 1:1. A prior lymphoproliferative or autoimmune disorder was present in 14 per cent of the patients. Signs of advanced disease were usually present from the onset, such as B symptoms (55 per cent), generalized lymphadenopathy (57 per cent), stage III/IV disease (62 per cent), and elevated levels of serum lactate dehydrogenase (68 per cent). Primary extranodal disease (14 per cent), hepatomegaly (12 per cent), splenomegaly (12 per cent), lung/pleural involvement (12 per cent), skin involvement (21 per cent), and bone marrow involvement (28 per cent) were uncommon. Lymphocytopenia was present in 64 per cent of the patients, and none of nine patients tested were serologically positive for human T-cell leukemia/lymphoma virus (HTLV-I) infection. Among 38 patients receiving combination chemotherapy, 20 (53 per cent) achieved a complete remission. The actuarial median survival of all patients was 17 months. Age greater than 60 years and stage III/IV disease predicted a poor clinical outcome, whereas the large cell histological subtype predicted a favourable outcome. Prospective clinical studies using uniform treatments and a uniform histologic classification scheme are needed to confirm these findings. PMID- 2888716 TI - Renal-limited polyarteritis nodosa. AB - A case of classic (large vessel) polyarteritis nodosa in which the disease was apparently confined in the kidneys is described. The findings in this case support the concept of renal-limited polyarteritis nodosa. PMID- 2888717 TI - Mapping of a restriction fragment length polymorphism within the human aldolase B gene. AB - Peripheral blood DNA was hybridized to the full-length cDNA and the cloned structural gene of human aldolase B. With PvuII endonuclease a restriction fragment length polymorphism was detected that was present in the heterozygous state in about 21% of the individuals tested. A map of the human aldolase gene was constructed for the two groups of individuals found to produce different fragments after PvuII digestion. This allowed the localization of the polymorphic site within the gene, which was found to be due to the loss of a PvuII site in the last intron upstream from the 3' end. This polymorphism may be used as a genetic marker to study individuals affected by hereditary fructose intolerance. PMID- 2888718 TI - Isolation of a polymorphic genomic clone from chromosome 7. Physical and genetic linkage studies to markers around the cystic fibrosis locus. AB - A peptide prepared from purified factor 13B (F13B) was sequenced, and a single, long oligonucleotide corresponding to its cognate DNA sequence was constructed and used to screen a chromosome 7 specific genomic library. The positive clone isolated, designated pKV13, was only related to F13B at the oligonucleotide region, but has proved to be a valuable chromosome 7 marker. pKV13 maps to 7pter q22 in hybrid cell lines, and is present in a chromosome-mediated gene transfer (CMGT) cell line that also contains met and other 7q probes. pKV13 defines a common MspI restriction fragment length polymorphism (RFLP), and is genetically linked to two markers on the long arm of chromosome 7, B79a and COLIA2, both themselves linked to the cystic fibrosis locus. Multipoint linkage analysis demonstrates that KV13 maps centromeric to both B79a and COLIA2. pKV13 has been used to demonstrate the existence of rearrangements within CMGT hybrids, and will also prove valuable in multipoint linkage studies of other 7q markers. Finally, pKV13 provides a new polymorphic locus for the characterisation of 7q deletions in myeloid disorders such as myelodysplastic syndrome. PMID- 2888719 TI - Detection of novel centromeric polymorphisms associated with alpha satellite DNA from human chromosome 11. AB - The pericentromeric region of human chromosomes is composed of diverse classes of repetitive DNAs, which provide a rich source of genetic variability. Here, we describe two novel centromeric polymorphisms associated with a subset of alpha satellite repetitive DNA, D11Z1, which is specific for human chromosome 11. Segregation and inheritance of the polymorphisms are demonstrated and their relative frequencies are determined. These polymorphisms may be useful genetic tools for distinguishing between individual chromosome 11 centromeres. In addition, these polymorphisms may be applied to the development of a centromere based genetic linkage map of chromosome 11. Molecular models for the generation of these polymorphisms are discussed. PMID- 2888720 TI - Close linkage of random DNA fragments from Xq 21.3-22 to X-linked agammaglobulinaemia (XLA). AB - Linkage analysis of 15 families affected by X-linked agammaglobulinaemia (XLA) showed close linkage with three probes located towards the centre of the long arm of the X chromosome. No cross-overs were found using pXG12 (DXS94) lod 6.6 or S21 (DXS17) lod 4.4. One cross-over was found with 19.2 (DXS3). This confirms and extends a previous linkage study (Kwan et al. 1986) which demonstrated linkage with S21 and 19.2. Of the families 14 were informative for either pXG12 or S21 and these probes should thus be of great diagnostic value. No evidence of heterogeneity was found in the XLA families but several cross-overs within this region were detected in a family with the X-linked hyper-IgM syndrome confirming this disease as a separate clinical entity. PMID- 2888721 TI - A hypervariable repeated sequence on human chromosome 1p36. AB - When used to probe Southern blots of TaqI-digested DNAs from unrelated individuals, p1-79, a 900 bp subclone of a random human cosmid, revealed at least 50 fragments, many of which were polymorphic. Each of 27 unrelated individuals tested with p1-79 displayed a distinct band pattern. Similar variation was seen with several other enzymes, including HaeIII, MspI, PstI and PvuII, whereas other enzymes yielded primarily large fragments of greater than 40 kb. In situ hybridization of p1-79 showed that the loci of hybridization are clustered on human chromosome band 1p36; localization of all TaqI fragments to chromosome 1 was confirmed with a human-rodent somatic cell hybrid panel. DNA sequencing of p1 79 revealed several copies of a 39 bp repeat whose variation in copy number might be the basis of the observed length polymorphisms. Studies of 3-generation Utah families suggest that the numerous restriction fragments homologous to p1-79 are inherited as haplotypes, implying that recombination within this cluster of loci is rare and allowing the cluster to serve as a useful marker for human gene mapping. PMID- 2888722 TI - Crossovers in two German cystic fibrosis families determine probe order for MET, 7C22 and XV-2c/CS.7. AB - We have followed the segregation of the probes pJ3.11, 7C22, pB79a, and MET through cystic fibrosis families in the German Democratic Republic with two affected sibs. Two families with a crossover between MET and the CF phenotype were detected. In one of these families recombination was also observed between the DNA probe 7C22 and CF, and between the markers XV-2c and CF, which suggests that XV-2c, MET and 7C22 are all on the same side of CF. The other MET recombinant family is informative with XV-2c and does not recombine, which excludes the genetic order XV-2c--MET--CF if multiple recombinant events are disregarded. These two families together demonstrate that recombinations may occur in a very small genetic interval, which has important implications for prenatal diagnosis based on data from linked markers. PMID- 2888723 TI - Construction of a chromosome 16-enriched phage library and characterization of several DNA segments from 16p. AB - A flow sorted chromosome 16-enriched recombinant library was produced to isolate DNA probes useful for constructing a linkage map of 16p, primarily for the study of adult polycystic kidney disease (APKD). The APKD locus has been mapped to chromosome 16 by linkage with the probe 3'HVR, which is located in the region 16p12----pter. Of the 48 single-copy fragments isolated from this new phage library, 39 (81%) were found to be chromosome 16 specific. Probes mapping to chromosome 16 were regionally localized by hybridizing to flow-sorted spot blots of translocation products from lymphoblastoid cell lines containing the rearrangements t(1;16) or t(11;16). Translocation breakpoints at 16p13.11 and 16p11.1 were utilized to subdivide chromosome 16 into three regions: Twenty-six probes were mapped to 16p11.1----16qter, two to 16p11.1----16p13.11, and eleven to 16p13.11----16pter. Probes from 16p were examined for their recognition of restriction fragment length polymorphisms (RFLPs). Seven polymorphic probes were found which recognized eleven RFLPs. Six of the seven probes have RFLPs which are reasonably informative (polymorphism information contents (PIC) of over 0.25). Two of these identify polymorphisms with three different alleles, one of which has a PIC value of over 0.4. These probes may aid in the diagnosis of APKD and contribute towards a linkage map of chromosome 16. PMID- 2888724 TI - Indirect haemagglutination test using gonococcal pilus antigen: how useful to diagnose gonorrhoea? AB - In 1979 an indirect haemagglutination test (gonococcal antibody test) using gonococcal pilus antigen replaced the gonococcal complement fixation test as our routine procedure to show gonococcal antibodies. In the diagnosis of current gonorrhoea the sensitivity of the gonococcal antibody test was far superior to that of the gonococcal complement fixation test (about 55% versus 9% for first episode gonorrhoea). To evaluate the usefulness of the test result the following population groups were studied: 1376 patients undergoing medical examination for gonorrhoea (386 had gonorrhoea), 1384 healthy people aged 15-65, 54 patients with meningococcal disease, 30 children with respiratory tract infection, and 254 patients with evidence of various diseases other than neisserial infections that might be associated with symptoms of arthritis. These investigations showed that (1) non-specific positive gonococcal antibody test results occur rarely, (2) at least half the people who have had gonorrhoea remain seropositive (with titres of 1/40 to 1/160), and (3) a positive test result is more significant the younger the patient and the higher the titre. For younger people a positive test result should always be followed up by bacteriological examination; in all age groups titres of 1/320 or more should indicate medical examination for current gonorrhoea. PMID- 2888725 TI - Action of anticytoskeletal compounds on in vitro cytopathic effect, phagocytosis, and adhesiveness of Trichomonas vaginalis. AB - The cytopathic effects of Trichomonas vaginalis treated with inhibitory concentrations of anticytoskeletal compounds (mebendazole, griseofulvin, colchicine, taxol, and cytochalasin B) were studied in mouse CLID fibroblast cultures. The evaluation, at different times, of cell numbers and morphological alterations showed that cytopathic effect was considerably reduced when protozoa were pretreated with mebendazole and griseofulvin, whereas colchicine, taxol, and cytochalasin B had less effect. Furthermore, treatment with mebendazole, griseofulvin, and colchicine decreased adhesiveness of the protozoan, whereas treatment with cytochalasin B and colchicine completely inhibited its phagocytic activity. From these results it may be concluded that alterations induced in the trichomonal cytoskeleton may affect its adhesiveness and its in vitro cytopathic effect, but there is no direct correlation between protozoan phagocytosis and its in vitro pathogenic effect. PMID- 2888726 TI - DNA polymorphism of human HLA-linked complement C4 allotypes, including C4 null alleles, in the Finnish population. AB - Human HLA-linked complement C4 gene products, C4A and C4B, show extensive genetic polymorphism. In both loci, an allele without a gene product, C4 null, is also observed. We have performed a restriction enzyme analysis of genomic DNA samples from individuals having all common (frequency over 1%) C4 protein allotypes observed in the Finnish population. Only one allotype-specific RFLP marker was observed. With some enzymes a DNA polymorphism was observed, which was not detectable by C4 protein typing. Analysis of 10 different C4B null haplotypes and 4 C4A null haplotypes suggested that only one haplotype, HLA-B8 C4A0 B1, carried a C4A gene deletion. This was observed in all 4 unrelated individuals homozygous for this haplotype. PMID- 2888727 TI - Allelic forms of the alpha- and beta-chain genes encoding DQw1-positive heterodimers. AB - On chromosome 6, in the HLA region, the DQ subregion is located immediately centromeric to the DR subregion. Even though only three serological specificities to date have been officially recognized (DQw1, DQw2, and DQw3), it seems likely that the phenotypical polymorphism expressed by DQ molecules is much more complex. There are reasons to believe that fixed alpha-beta combinations exist, each of them associated with a different DR allele. DQw1 is a determinant present on DQ molecules that are found associated with DR1-, DR2-, and DRw6-positive haplotypes. By restriction fragment length polymorphism analysis, we recognized three allelic DQ-alpha and three allelic DQ-beta patterns associated with DQw1. In addition, one of these alpha/beta pairs associated with DR1, two with DR2, and a fourth with DRw6. We have obtained evidence using nucleotide sequencing that there are as many allelic forms of DQ-alpha and DQ-beta genes as there are different molecular DQ-alpha and DQ-beta patterns. The DQ-alpha and DQ-beta chains of DQw1-positive molecules each are encoded by at least three distinctly different allelic genes, and particular alpha/beta gene combinations are associated with the same DR alleles as their corresponding molecular alpha/beta pairs. PMID- 2888728 TI - HLA-DQw3.2 allele of the DR4 haplotype is associated with insulin-dependent diabetes; correlation between DQ beta restriction fragments and DQ beta chain variation. PMID- 2888729 TI - H-T5 and H-T16, recognized by T-cell clones, are encoded by a gene(s) linked to Thy-1.2. PMID- 2888730 TI - Recognition of the galactose- or N-acetylgalactosamine-binding lectin of Entamoeba histolytica by human immune sera. AB - Cure of amebic liver abscess is associated with resistance to recurrent invasive amebiasis and the development of a humoral and cell-mediated immune response. We determined whether human immune sera contain blocking antibody for the 170 kilodalton (kDa) galactose or N-acetylgalactosamine (Gal/GalNAc)-binding lectin of Entamoeba histolytica. By Western blot (immunoblot) of whole amebae subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, all eight immune sera studied here prominently recognized a 170-kDa amebic protein. Western blot of the purified Gal/GalNAc lectin with pooled human immune sera (PHIS) confirmed that the 170-kDa band was the adherence lectin. Immunoprecipitation of [35S]methionine-metabolically-labeled amebae with the antilectin monoclonal antibody H8-5 and with PHIS demonstrated that the 170-kDa lectin was the major antigen recognized by PHIS. The in vitro adherence of E. histolytica trophozoites to CHO cells at 4 degrees C was inhibited by prior exposure of amebae to greater than or equal to 1.0% PHIS. The humoral response to the Gal/GalNAc-binding lectin of the parasite may contribute to the development of protective immunity against invasive amebiasis. PMID- 2888731 TI - The erythrocyte and epithelial cell receptors for Haemophilus influenzae are expressed independently. AB - The Anton blood group antigen has been shown to be the erythrocyte receptor for Haemophilus influenzae. Cord erythrocytes, which lack the Anton antigen, were not agglutinated by H. influenzae (L. van Alphen, J. Poole, and M. Overbecke, FEMS Microbiol. Lett. 37:69-71, 1986). Twenty-eight erythrocyte suspensions from newborns less than 4 days old were also not agglutinated, but 23 of 56 erythrocyte suspensions from 4- to 50-day-old newborns and 23 of 35 erythrocyte suspensions from older infants were agglutinated. Positive hemagglutination correlated with the presence of the Anton antigen on the erythrocytes for 163 of 173 (P less than 0.0001). Adherence of H. influenzae to buccal epithelial cells obtained from six newborns within 3 days after birth was as strong as that found with adult epithelial cells, whereas the erythrocytes from five of six of these newborns were not agglutinated by the bacteria. Adherence of H. influenzae to epithelial cells of 15 donors was not inhibited by anti-Anton serum. Moreover, H. influenzae carrying fimbriae adhered to epithelial cells of an Anton-negative donor. From these results we conclude that the age at which the erythrocyte receptor for H. influenzae is expressed is the same as for the Anton antigen, but that the receptor on the epithelial cells is already expressed at birth and is not identical to the Anton antigen. PMID- 2888732 TI - Characterization of plasmids encoding the adherence factor of enteropathogenic Escherichia coli. AB - Volunteer studies have shown that a 60-megadalton plasmid is required for full virulence of the human enteropathogenic Escherichia coli (EPEC) strain E2348/69 (O127:H6). The plasmid, designated pMAR2, encodes localized adherence to HEp-2 cells in tissue culture via the adhesin known as the EPEC adherence factor (EAF). Using a DNA probe for the EAF, we have previously shown that these genes are specific for EPEC and are usually encoded on plasmids ranging from 55 to 65 megadaltons. In this study, Southern blot analysis and S1 nuclease homology determination reveal a high degree of sequence conservation among these plasmids, despite some variation in restriction maps. Phenotypic characterization of the prototype EAF plasmid pMAR2 reveals that the plasmid belongs to the group IncFII and is negative for alpha-hemolysin, colicin, and aerobactin synthesis, as well as biochemical markers and antibiotic resistance. Regions encoding adherence to HEp-2 cells were localized by Tn801 insertion mutagenesis. Adherence genes were then cloned as two distinct plasmid regions which confer the adherence phenotype only when complementing each other in trans. PMID- 2888733 TI - Construction and characterization of Bordetella pertussis toxin mutants. AB - Pertussis toxin is one of the major virulence determinants produced by Bordetella pertussis. The DNA encoding the structural genes for pertussis toxin was cloned in Escherichia coli, and pertussis toxin subunit S4 was expressed under the control of the tac promoter. Mutations were introduced into the cloned toxin genes, and a conjugative shuttle vector system was devised for delivering the mutations from E. coli back into B. pertussis. The mutations were introduced by allelic exchange into the chromosome of B. pertussis resulting in a series of B. pertussis strains which were isogenic except at the loci encoding the structural genes for pertussis toxin. These B. pertussis strains were utilized to study the biogenesis of pertussis toxin. Polar mutations in the S1 gene led to a lack of detectable S2 or S4 subunits in whole-cell lysates, suggesting a polycistronic arrangement for these genes. Mutations in the S5 subunit gene resulted in a truncated S1 subunit, while mutations in the S4 gene resulted in a lack of detectable S2 subunit, suggesting that physical relationships among the toxin subunits are directly reflected in the stable biogenesis of the subunits. PMID- 2888734 TI - Influences of conjugal genetic transfer functions of colicin V plasmids on adhesion of Escherichia coli to murine intestinal tissue. AB - Cells of strains of Escherichia coli K-12 291 bearing one of three colicin V plasmids, pF54, pH247, or pF70, were tested in comparison with cells of strain 291 for their ability to adhere to murine intestinal tissue in vitro. The plasmids were either repressed or derepressed in conjugal genetic transfer functions. The strains bearing pF54 and pH247 repressed in transfer functions (pColVF54 luminal diameter r and pColVH247 luminal diameter r) adhered in higher numbers to the murine tissue than did the host strain lacking the plasmid or the strains containing the plasmids with active transfer functions (pColVF54drd and pColVH247drd). The number of cells (CFU) of strain 291(pColVF54 luminal diameter r) adherent to the tissue was related directly to the time of incubation (up to 30 min) and to the number of cells (CFU) to which the tissues were exposed. As indicated by tests for sensitivity to F factor (F)-pilus-specific bacteriophages, the cells of strains bearing the plasmids derepressed for conjugal functions had F pili on their surfaces, while such structures were missing from cells of the parental strain (291) and the strains containing the plasmids in repressed form. This finding was supported by transmission electron microscopy of cells of strain 291, 291(pColVF54 luminal diameter r), and 291(pColVF54drd). F pili could be seen on cells of the latter strain but not on those of the parental strain or the strain bearing pColVF54 luminal diameter r. Pili other than F pili were not seen on cells of the strains bearing pF54 in either form. Strains 291(pColVF70drd) and 291(pColVF70 luminal diameter r) adhered to the tissues in numbers comparable to those of strain 291. Nevertheless, these findings are further evidence that for certain colicin V plasmids (A. M. Nilius and D. C. Savage, Infect. Immun. 43:947 953, 1984), conjugal genetic transfer functions influence properties that may be important in the pathogenesis of invasive E. coli strains. PMID- 2888735 TI - Hyperthermia and human spermatogenesis: enhancement of the inhibitory effect obtained by 'artificial cryptorchidism'. AB - Decreased sperm count and motility were observed in men after induction of local testicular hyperthermia by raising the testicles into the inguinal canal during the day in adult volunteers. A similar technique in which the testicles were better maintained in the inguinal canal resulted in more marked suppression of spermatogenesis. As assessed by the total motile sperm count, the mean inhibitory effect of hyperthermia was at least 97% after 2 months using this technique. This effect of 'artificial cryptorchidism' may be of practical interest in the manipulation of male fertility. PMID- 2888736 TI - Pharmaco-EEG and psychometric studies with a novel selective benzodiazepine agonist/antagonist Ro 23-0364. AB - In a double-blind, placebo-controlled study, the encephalotropic and psychotropic properties of Ro 23-0364, a novel imidazobenzodiazepine with mixed benzodiazepine agonist/antagonist properties, were investigated as compared with the pure agonist diazepam utilizing quantitative EEG and psychometric analyses as well as clinical observations. Ten normal volunteers received randomized (latin square) and at weekly intervals single oral doses of placebo, 0.25 mg, 0.5 mg and 1.0 mg Ro 23-0364 and 10 mg diazepam as reference drug. EEG-recordings and evaluation of pulse, blood pressure and side effects were carried out at the hours 0, 1, 2, 4, 6, and 8; psychometric tests at the same times except the first hour. Computer assisted spectral analyses of the EEG demonstrated after 10 mg diazepam a typical "anxiolytic" pharmaco-EEG profile characterized by an increase of beta-activity, decrease of alpha-activity and absolute and relative power of the dominant frequency, furthered by an acceleration of the centroid of the total activity and a slowing of the centroid of the combined delta/theta-activity. In addition, there was an increase of delta-activity specifically in the resting recording condition suggesting also sedative properties of the reference compound. Ro 23 0364 induced in the vigilance-controlled recordings a similar profile as diazepam although less pronounced-thereby exhibiting tranquilizing qualities. However, in the resting condition the most consistent change was an augmentation of delta/theta-activity along with an attenuation of alpha-activity, which was evident already in the lower dosage range and is reminiscent also of changes seen after sedative neuroleptic drugs (although the centroid slowing was missing). These data indicate a selective sedation of the mixed agonist/antagonist in the resting state. Dose-efficacy calculations based on EEG-changes demonstrated the reference compound, 1.0 and 0.5 mg Ro 23-0364 different from placebo. 10 mg diazepam was by far the most CNS-active compound inducing significantly more changes than the three doses of the mixed agonist/antagonist. Within the latter the two higher doses were superior to 0.25 mg but could not be differentiated from each other. Time-efficacy calculations showed the maximal encephalotropic effect of diazepam within the first two hours while the peak effect of 1.0 mg and 0.5 mg Ro 23-0364 fell into the 6th and 4th hour, respectively. There were no differences between the time periods after 0.25 mg although there was a trend towards high activity in the first two hours followed by a trough in the 4th and 6th hour and thereafter again an increase.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2888737 TI - Effect of bucindolol on plasma HDL cholesterol subfractions and other plasma lipids in essential hypertensive patients. AB - The effect on plasma lipids of a new beta-blocker bucindolol, which possesses weak alpha-adrenergic blocking property and intrinsic sympathomimetic activity, given orally over a 3-month period as a monotherapy or with a thiazide diuretic to 44 patients with essential hypertension was studied. The mean level of plasma HDL cholesterol concentration increased significantly during 3 months monotherapy with bucindolol or with bucindolol and diuretic. This increase was due to the increase of HDL3 subfraction. There were no significant changes in the concentrations of plasma triglycerides or total cholesterol during treatment. The ratio of HDL cholesterol to total cholesterol increased significantly. The concentration of apoprotein A-I decreased significantly in both treatment groups, but the level of apoprotein B remained constant among treatment groups. The results support the earlier observations that beta-adrenergic blocking agents with different pharmacologic properties differ as regard to their effects on plasma lipids and lipoproteins. PMID- 2888738 TI - Pharmacokinetics of famotidine in man. AB - Famotidine (F) is an effective new H2-receptor antagonist. Knowledge of its pharmacokinetic properties and metabolism is scanty. Therefore, we investigated the disposition of F in 6 healthy male volunteers following a single oral (40 mg) and intravenous (20 mg) dose. F and a metabolite were monitored in plasma or urine by a HPLC method. After intravenous administration plasma levels declined biexponentially with an initial half-life (t1/2) of 0.5 h and a terminal t1/2 of 4.0 h. F was slightly bound to plasma proteins (less than 1 to 15%) and its distribution volume averaged 1.13 l/kg. About 72% of the dose could be recovered as unchanged F in urine. Thus, hepatic clearance contributes to the total plasma Cl of 309 ml/min only 88 ml/min. Consequently, a high hepatic first-pass effect can be excluded. Following oral administration maximum plasma concentrations of 104 +/- 39 ng/ml (mean +/- SD) were observed after 2.3 +/- 1 h. F was eliminated with a t1/2 of 3.6 +/- 1.1 h and its absolute bioavailability ranged from 20 to 66%. In urine an oxidized metabolite could be identified which accounts to about 2% of the given dose. In conclusion, F is rapidly eliminated mainly by the renal route and its t1/2 is slightly longer than those of other available H2-receptor antagonists. PMID- 2888739 TI - Opiates in the restless legs syndrome. PMID- 2888740 TI - The antianxiety agents. PMID- 2888741 TI - [Adult T-cell leukemia--from retrovirus-induced T-cell leukemia in dermatologic patients. Clinical histologic and epidemiologic studies]. AB - In 1976, adult T-cell leukemia (ATL) was reported as a special form of T-cell leukemia. In such cases the following criteria are prominent: strong inclination to leukemic change, incidence of abnormal cells in the peripheral blood, and the existence of an endemic area at the time of the outbreak of the disease. The abnormal tissue infiltrating ATL cells originate from peripheral blood T lymphocytes, and in these lymphocytes the causal retrovirus HTLV-I could be proven. Since pathognomonic cutaneous manifestations can be observed among almost 50% of the patients, knowledge of this disease is of great importance to dermatologists. Two cases are reported focussing on the clinical and histopathologic findings concerning the cutaneous manifestations. Epidemiologically, up to 1984, we collected and analyzed 153 Japanese cases. There is a minor difference in sex distribution, but the incidence of ATL is highest among people in their fifties. The region of Kyushu, especially the southwestern part, and of Okinawa proved to be the endemic centers of ATL. PMID- 2888742 TI - Peptidergic innervation of the rat Harderian gland. AB - The immunohistochemical localization of vasoactive intestinal polypeptide (VIP), Neurotensin (NT), cholecystokinin (CCK), Neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) in rat Harderian glands was examined. Numerous VIP- and CCK-like immunoreactive nerves were found in close apposition to the acini. Sparse numbers of NT-, NPY-, and CGRP-like immunoreactive nerves were observed in close proximity to the acini and blood vessels. Some VIP-like immunoreactive nerves were shown to be co-localized with acetylcholinesterase-positive cholinergic nerves. PMID- 2888743 TI - Sexual difference in the histochemical characteristics of "altered cell foci" in the liver of aged Fischer 344 rats. AB - The distributions of gamma-glutamyltransferase (GGT) and the placental form of glutathione S-transferase (GSTP) were examined in the livers of 18-month-old and 23-month-old SPF F344/DuCrj rats of both sexes. The number of the enzyme-altered foci in males was greater than in females, and it increased with age in animals of both sexes. Histologically, most of the foci in males consisted of eosinophilic or clear hepatocytes, while those in females were predominantly basophilic. More than 75% of the foci in males stained positively for GGT and GSTP. In contrast, more than 80% of the foci in females were GGT- and GSTP negative. Thus, though both enzymes have been widely used for analysis of carcinogen-induced hepatocarcinogenesis, it appears that GGT and GSTP are inappropriate as markers of preneoplastic lesions in natural hepatocarcinogenesis in female rats. PMID- 2888744 TI - A note on adhesion of bacteria to chicken muscle connective tissue. AB - Laboratory cultures of bacteria were tested for the ability to attach to collagen fibres of intact chicken muscle connective tissue. All salmonellas, fimbriate strains of Escherichia coli and a strain of Campylobacter coli were able to attach to tissue only when suspended in distilled water. Prior immersion of tissue in sterile water for 20 min or extended immersion in these bacterial suspensions was a prerequisite for adhesion. Attachment could be prevented by the addition of physiological levels of sodium chloride to the attachment medium. Furthermore, attached bacteria could be removed by rinsing tissues in saline media. PMID- 2888745 TI - Role of the parasympathetic nervous system in airway hyperresponsiveness after ozone inhalation. AB - Airway hyperresponsiveness develops in dogs after ozone inhalation. This study examined the role of the parasympathetic nervous system in ozone-induced airway hyperresponsiveness in dogs. Dose-response curves to acetylcholine (n = 8) and histamine (n = 4) were measured before and after exposure to ozone (3 ppm for 30 min). The provocative concentration of each agonist was measured on two randomly assigned days separated by at least 1 wk. On one day a control experiment was performed, and on the other day the dogs were pretreated with the ganglionic blocker hexamethonium bromide in doses that block ganglionic transmission. The acetylcholine provocative concentration decreased on the control day from 5.5 mg/ml (%SE 1.8) before ozone to 0.5 mg/ml (%SE 2.0) after ozone (P less than 0.0001). After pretreatment with hexamethonium the acetylcholine provocative concentration decreased from 9.0 mg/ml (%SE 1.8) before ozone to 1.0 mg/ml (%SE 2.0) after ozone (P = 0.002). The results were similar when histamine was used as the agonist. Therefore, ganglionic blockade does not prevent airway hyperresponsiveness after ozone inhalation, and a parasympathetic reflex mechanism is not responsible for airway hyperresponsiveness after ozone inhalation in dogs. PMID- 2888746 TI - Possible sensory receptor of nonadrenergic inhibitory nervous system. AB - To determine the sensory receptor of the nonadrenergic inhibitory nervous system (NAIS), 22 cats were anesthetized and serotonin was continuously administered (50 250 micrograms.kg-1.min-1 iv) to increase pulmonary resistance (RL) to 377 +/- 57% (SE) of the control value. We then 1) mechanically irritated the trachea, 2) intravenously administered capsaicin (5 micrograms/kg), or 3) induced hypoxia (arterial PO2 30-40 Torr) to stimulate irritant and bronchial C-fiber receptors, pulmonary C-fiber receptors, or the carotid body (chemoreceptors), respectively. After treatment with atropine (3 mg/kg iv) and propranolol (2 mg/kg iv), the serotonin-induced change in RL was reduced by 58.6 +/- 14.3% by mechanical irritation and 63.3 +/- 12.1% by intravenous capsaicin. However, hypoxia produced no dilatation of the airways. In further experiments, we employed capsaicin inhalation to stimulate bronchial C-fiber receptors. Inhaled capsaicin (0.1%, for 5 breaths) also reduced RL by 79.2 +/- 9.2% of the elevated value, after atropine and propranolol. Treatment with a ganglionic blocking agent, hexamethonium (2 mg/kg iv), abolished bronchodilator responses, implying that a reflex pathway through vagal nerves is involved in this phenomenon. These results suggest that pulmonary and bronchial C-fiber receptors may be involved as sensory receptors in NAIS reflex bronchodilatation. PMID- 2888747 TI - Hematologic consequences of viral infections. AB - This article summarizes the current medical literature regarding the effects of viral infections upon the hematopoietic system. The article discusses the effect of viral infections upon peripheral blood counts, cellular immune system, and the bone marrow. In addition, a few selected syndromes, including human parvovirus, EBV, and HTLV infections, are discussed. PMID- 2888748 TI - Activation of tyrosinase in mouse melanoma cell cultures. AB - Tyrosinase activity increased in Cloudman S-91 mouse melanoma cell homogenates incubated at 37 degrees C for a minimum of 8 h. Enzyme activity continued to increase for 48 h at which time the maximal level of activation was observed. Activation did not occur at 4 degrees C and did not occur in the cytosol fraction of the cell, suggesting that the response was localized to melanosomes. The activated enzyme was resistant to solubilization with the nonionic detergent, Triton X-100, and preparation of homogenates in this detergent did not inhibit the temperature-dependent activation of the melanosomal fraction of the cell. The activation process increased the Vmax of tyrosinase 10-fold and lowered the Km by a factor of 2 as determined by the tyrosine hydroxylase assay. The increase in tyrosinase activity was detectable by three assay methods: tyrosine hydroxylation, melanin synthesis, and by tyrosine decarboxylation. The formation of melanin, however, was found to be 1/20 that of either tyrosine hydroxylation or decarboxylation, a finding which suggests that the melanin pathway may be blocked at 5,6-dihydroxyindole. The "self-activation" response could not be mimicked by incubating cell homogenates with cyclic AMP-dependent protein kinase. Activated tyrosinase could be inhibited by the addition of fresh cell extracts, a finding which suggests that tyrosinase inhibitors may be present in these cells. PMID- 2888749 TI - Multiple endocrinal neoplasia. PMID- 2888750 TI - Role of glutamate dehydrogenase in ammonia assimilation in nitrogen-fixing Bacillus macerans. AB - Pathways of ammonia assimilation into glutamic acid in Bacillus macerans were investigated by measurements of the specific activities of glutamate dehydrogenase (GDH), glutamine synthetase, and glutamate synthase. In ammonia rich medium, GDH was the predominant pathway of ammonia assimilation. In nitrogen fixing cells in which the intracellular NH4+ concentration was 1.4 +/- 0.5 mM, the activity of GDH with a Km of 2.2 mM for NH4+ was found to be severalfold higher than that of glutamate synthase. The result suggests that GDH plays a significant role in the assimilation of NH4+ in N2-fixing B. macerans. PMID- 2888751 TI - Purification and characterization of the F1 ATPase from Bacillus subtilis and its uncoupler-resistant mutant derivatives. AB - The F1 ATPase of Bacillus subtilis BD99 was extracted from everted membrane vesicles by low-ionic-strength treatment and purified by DEAE-cellulose chromatography, hydrophobic interaction chromatography, and anion-exchange high performance liquid chromatography. The subunit structure of the enzyme was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the absence and presence of urea. In the absence of urea, the alpha and beta subunits comigrated and the ATPase was resolved into four bands. The mobility of the beta subunit, identified by immunoblotting with anti-beta from Escherichia coli F1, was altered dramatically by the presence of urea, causing it to migrate more slowly than the alpha subunit. The catalytic activity of the ATPase was strongly metal dependent; in the absence of effectors, the Ca2+-ATPase activity was 15- to 20-fold higher than the Mg2+ -ATPase activity. On the other hand, sulfite anion, methanol, and optimally, octylglucoside stimulated the Mg2+ -ATPase activity up to twice the level of Ca2+ -ATPase activity (specific activity, about 80 mumol of Pi per min per mg of protein). The F1 ATPase was also isolated from mutants of B. subtilis that had been isolated and characterized in this laboratory by their ability to grow in the presence of protonophores. The specific activities of the ATPase preparations from the mutant and the wild type were very similar for both Mg2+- and Ca2+ -dependent activities. Kinetic parameters (Vmax and Km for Mg-ATP) for octylglucoside-stimulated Mg2+ -ATPase activity were similar in both preparations. Structural analysis by polyacrylamide gel electrophoresis and isoelectric focusing indicated that the five F1 subunits from ATPase preparations from the mutant and wild-type strains had identical apparent molecular weights and that no charge differences were detectable in the alpha and beta subunits in the two preparations. Thus, the increased ATPase activity that had been observed in the uncoupler-resistant mutants is probably not due to a mutation in the F1 moiety of the ATPase complex. PMID- 2888752 TI - Genetic instability and DNA amplification in Streptomyces lividans 66. AB - Streptomyces lividans 66 exhibits genetic instability, involving sequential loss of resistance to chloramphenicol (Cams) and subsequent mutation of argG. Associated with this instability is the amplification of a 5.7-kilobase (kb) amplified DNA sequence (ADS). We have characterized a second, independent pathway of genetic instability, involving sequential loss of resistance to tetracycline (Tets) followed by mutation in nitrogen assimilation (Ntr). We detected DNA amplification in many of these mutant strains, as well as other reiterations coresident with the 5.7-kb ADS in Cams Arg mutants. However, in contrast to the 5.7-kb ADS, none of the novel elements were observed to amplify at high frequency. The mutation of argG is due to a deletion, one endpoint of which is defined by the 5.7-kb ADS. This amplification derives from a structure, the tandemly duplicated amplifiable unit of DNA (AUD), present in the wild-type genome. We found that progenitor strains containing just a single-copy AUD failed to reproducibly generate amplification of this element in Cams argG mutants, and DNA deletion endpoints proximal to the element were found to be unspecific. These results suggest that a duplicated AUD structure is required for high-frequency amplification and that this reiteration can subsequently buffer the extent of deletion formation in the relevant chromosomal region. PMID- 2888753 TI - A Lewis X hapten is the major glycolipid of Japanese quail intestine. AB - A fucolipid isolated from Japanese quail intestine was identified as beta galactosyl-1,4-(alpha-fucosyl-1,3-) beta-N-acetylglucosaminyl-1,3-beta-galactosyl 1,4-beta-glucosyl-1,1-cera mide, a glycolipid which exhibits X-hapten activity. Analysis of the tissue at various embryonic stages showed that the fucolipid is characteristically present at later stages of organogenesis. PMID- 2888754 TI - Effect of amino acid at the beta 6 position on surface hydrophobicity, stability, solubility, and the kinetics of polymerization of hemoglobin. Comparisons among Hb A (Glu beta 6), Hb C (Lys beta 6), Hb Machida (Gln beta 6), and Hb S (Val beta 6). AB - Surface hydrophobicity, stability, solubility, and kinetics of polymerization were studied using hemoglobins with four different amino acids at the beta 6 position: Hb A (Glu beta 6), Hb C (Lys beta 6), Hb Machida (Gln beta 6), and Hb S (Val beta 6). The surface hydrophobicity increased in the order of Hb C, Hb A, Hb Machida, and Hb S, coinciding with the hydrophobicity of the amino acid at the beta 6 position. Solubility of the oxy-form of these hemoglobins decreased in relation to increases in their surface hydrophobicity, suggesting that the solubility is controlled by the strength of hydrophobicity of the amino acid at the beta 6 position. The solubility of the oxy-form of these hemoglobins is always higher than that of the deoxy-form. There is a similar linear relationship between the solubility and surface hydrophobicity among deoxyhemoglobins A, C, and Machida. However, the solubility of deoxy-Hb S deviated significantly from the expected value, indicating that the extremely low solubility of deoxy-Hb S is not directly related to the hydrophobicity of the beta 6 valine. Kinetic studies on the polymerization of deoxy-Hb Machida revealed a distinct delay time prior to polymerization. This confirms our previous hypothesis that beta 6 valine is not responsible for the delay time prior to gelation. The kinetics of the polymerization of 1:1 mixtures of sickle and non-sickle hemoglobins were similar to those of pure Hb S, suggesting that only one of the two beta 6 valines is involved in an intermolecular contact. In mixtures of equal amounts of Hb S and Hb A, Hb C, or Hb Machida, half of the asymmetrical AS, SC, and S-Machida hybrid hemoglobins behaved like Hb S during nucleation, while the other half behaved like the non-sickle hemoglobin. PMID- 2888755 TI - Influence of cell-cell contact on levels of tyrosine hydroxylase in cultured bovine adrenal chromaffin cells. AB - We have studied the regulation of tyrosine hydroxylase by cell-cell contact in primary cultures of bovine adrenal chromaffin cells. Preparation of dissociated chromaffin cells from bovine adrenal medullae or the harvesting of cultured cells resulted in a rapid decrease of the specific mRNA(TH) (defined as the amount of mRNA(TH) (where TH represents tyrosine hydroxylase) per microgram of total RNA). The decrease in mRNA(TH) levels appears to be stimulated by the loss of cell contact, as it occurs much more rapidly than would be expected from the turnover rate of mRNA(TH) in cultured cells. Similarly an enhanced rate of tyrosine hydroxylase enzyme degradation was observed in chromaffin cells when brought into low contact cultures. In contrast to the decrease in mRNA(TH) levels, however, the decrease in tyrosine hydroxylase enzyme levels was not so rapid and could be prevented in high contact cultures. The mRNA(TH) increased 4-fold in high contact cultures relative to dissociated cells within 1 day after plating. Similarly the rate of synthesis of tyrosine hydroxylase enzyme molecules was maximal after 1 day, although the increase in the absolute amount of tyrosine hydroxylase occurred only slowly. The increase in specific mRNA(TH) by cell contact was inhibited by alpha-amanitin, indicating that cell contact evokes an increase in tyrosine hydroxylase levels by increasing the transcription of mRNA(TH), in addition to inhibiting the degradation of tyrosine hydroxylase molecules. PMID- 2888756 TI - Subunit interaction elicited by partial inactivation with L-methionine sulfoximine and ATP differently affects the biosynthetic and gamma glutamyltransferase reactions catalyzed by yeast glutamine synthetase. AB - Yeast glutamine synthetase can be irreversibly inactivated in the presence of L methionine sulfoximine, ATP, and a divalent cation Mn2+ or Mg2+. Kinetic studies with partially inactivated enzymes show that inactivation of a given subunit in the octameric glutamine synthetase affects the activities of its neighboring subunit such that the rate of the inactivation as well as the gamma glutamyltransferase activity of the noninactivated subunits decreases while their biosynthetic activity is enhanced. This outcome of subunit interaction is the same irrespective of whether Mn2+ or Mg2+ is used to fulfill the divalent cation requirement of glutamine synthetase for the inactivation reaction and the gamma glutamyltransferase reaction. Although only Vmax is affected in the gamma glutamyltransferase assay, both Km (glutamate) and Vmax are changed in the biosynthetic assay. PMID- 2888757 TI - Ethanol-elicited alterations in the oligomycin sensitivity and structural stability of the mitochondrial F0 . F1 ATPase. AB - Liver mitochondria from rats fed ethanol chronically demonstrated a 35% decrease in mitochondrial ATPase activity. Moreover, the ATPase activity was inhibited only 61% by addition of oligomycin. Treatment of mitochondria from ethanol-fed rats with the detergent, Lubrol-WX, caused the release of 36% of the F1 from the resulting inner membrane particles. In comparison, only 5% of the F1 was dissociated when control mitochondria were subjected to the Lubrol treatment. However, when the units of ATPase activity from the supernatant and particles obtained after Lubrol treatment were added together, their sums were equivalent in preparations from control and ethanol-fed animals. Moreover, polyacrylamide gel electrophoresis analyses indicated equal amounts of the alpha + beta subunits of F1 in mitochondria from control and ethanol-fed rats. Reconstitution experiments with urea particles and F1 prepared from both control and ethanol mitochondria revealed a decrease in oligomycin sensitivity which could be attributed to an alteration in the functioning of either the oligomycin sensitivity conferring protein or a membrane sector subunit that interacts with oligomycin. Analysis by reconstitution also demonstrated that there were no ethanol-elicited alterations in the properties of the F1 portion of the ATP synthase complex. These observations indicate that the activity of the ATP synthase complex is altered significantly by ethanol-elicited changes in the functioning of those polypeptides involved in modulating both oligomycin sensitivity and the association of F1 with membrane sector subunits. PMID- 2888758 TI - Hormonal regulation of myosin heavy chain and alpha-actin gene expression in cultured fetal rat heart myocytes. AB - Thyroid hormone regulates the expression of ventricular myosin isoenzymes by causing an accumulation of alpha-myosin heavy chain (MHC) mRNA and inhibiting expression of beta-MHC mRNA. However, the mechanism of thyroid hormone action has been difficult to examine in vivo because of its diverse actions. Accordingly, hormonal control of expression of six MHC isoform mRNAs and cardiac and skeletal alpha-actin mRNAs was studied in primary cultures of fetal rat heart myocytes grown in defined medium. The results indicate that in the absence of thyroid hormone, cultured heart cells express predominantly beta-MHC and cardiac alpha actin mRNAs. Addition of 3,5,3'-triiodo-L-thyronine (T3) caused a rapid induction of alpha-MHC mRNA and decreased beta-MHC mRNA levels without affecting the skeletal muscle MHC mRNAs. There was an almost parallel change in the myosin isoenzymes. Cardiac alpha-actin mRNA levels were transiently increased by T3 treatment, but skeletal alpha-actin was unaffected. Elimination of insulin and epithelial growth factor from the medium did not alter the effects of T3 on cardiac MHC mRNA expression. Addition of various adrenergic agents to the medium had no appreciable effect on cardiac MHC mRNA expression despite the presence of functionally coupled alpha- and beta-adrenergic receptors. Addition of steroid hormones, muscarinic agents, and glucagon to the medium also had no effect. Thus, under defined conditions, T3 is able to regulate MHC gene expression at a pretranslational level without the need for other exogenous factors. PMID- 2888759 TI - Tryptophan synthase alpha subunit glutamic acid 49 is essential for activity. Studies with 19 mutants at position 49. AB - We have obtained a complete set of 20 variants of the alpha subunit of tryptophan synthase of Escherichia coli at position 49 in order to extend our previous studies on the effects of single amino acid replacements at position 49 on structure and function. Thirteen mutant alpha subunits have been newly constructed by site-directed mutagenesis using oligonucleotides. Six mutants were available from previous studies. We find that the wild type and all of the mutant alpha subunits form alpha 2 beta 2 complexes with the beta 2 subunit of tryptophan synthase with similar association constants and similarly stimulate the activity of the beta 2 subunit in the synthesis of L-tryptophan from L-serine and indole. Thus none of the changes at position 49 produces a change in the conformation of the alpha subunit which significantly interferes with normal subunit interaction. However, the 19 mutant alpha 2 beta 2 complexes are completely devoid of activity in reactions normally catalyzed by the active site of the alpha subunit. This is the first time that these several activities have been measured with a series of highly purified alpha subunits altered by mutation at a single site. Our finding that the mutant in which glutamic acid 49 is substituted by aspartic acid is totally devoid of alpha activity is especially significant and is strong evidence that glutamic acid 49 is an essential catalytic base in the reaction catalyzed by the alpha subunit. This result is consistent with the results of previous genetic studies, with evolutionary comparisons using sequence analysis, and with recent results from x-ray crystallography of the alpha 2 beta 2 complex of tryptophan synthase from Salmonella typhimurium. PMID- 2888760 TI - The effects of chloroplast coupling factor reduction on the energetics of activation and on the energetics and efficiency of ATP formation. AB - There are two separate aspects to the energetic control over the initiation of ATP formation by chloroplast thylakoid membranes: (i) the free energy requirement for the phosphorylation of ADP and (ii) the energy-dependent transformation of the coupling factor into a catalytically active state. Using flash excitation, we have been able to distinguish between limitations imposed on ATP formation by the energetics of coupling factor activation from limitations imposed by the thermodynamics of ADP phosphorylation. We have placed particular emphasis on the effects of coupling factor reduction. ATP hydrolysis, ATP synthesis, and the release of tightly bound [14C]ADP were initiated by fewer flashes in thylakoid membranes in which the coupling factors were prereduced than in membrane samples in which the coupling factor remained oxidized. Only under conditions in which ATP synthesis occurred against a large chemical potential (i.e. delta GATP) did the onset of net ATP synthesis require a larger electrochemical potential than did the activation of the coupling factor. Thus, only at delta GATP values greater than about 51 kJ.mol-1 for thylakoid membranes with oxidized coupling factors and about 45 kJ.mol-1 when the coupling factors are reduced was the onset of ATP synthesis dictated by the thermodynamic equilibrium between ATP and ADP. At lower delta GATP values, the electrochemical potential became energetically adequate to phosphorylate ADP prior to becoming adequate to activate the coupling factor. These data indicate that reduction of the coupling factor lowers the delta pH necessary for activation from approximately 2.9 to approximately 2.6 units. Accompanying the lower energetic requirement for the activation of the reduced coupling factor was an increase in the efficiency of ATP synthesis under conditions of limiting energization. PMID- 2888761 TI - Is pyrophosphate an analog of adenosine diphosphate for beef heart mitochondrial F1-ATPase. AB - Beef heart mitochondrial F1 possesses three pyrophosphate-binding sites, which comprises one high affinity binding site (Kd approximately equal to 1 microM) and two lower affinity sites (Kd approximately equal to 20 microM). High affinity pyrophosphate binding required the presence of Mg2+ in the incubation medium. Pyrophosphate competed with ADP, but not with Pi for binding to mitochondrial F1. Upon binding of 3 mol of pyrophosphate/mol of F1, one of the three tightly bound nucleotides present in native F1 was released. Like ADP and in contrast to Pi, pyrophosphate enhanced the fluorescence intensity of F1-bound aurovertin, and it prevented the photolabeling of F1 by 2-azido-ADP. As aurovertin and 2-azido-ADP are ligands of the beta subunit of F1, it is likely that pyrophosphate binds preferentially to the beta subunit. Whereas the binding affinity of F1 for Pi was increased by concentrations of pyrophosphate lower than 100 microM, it was decreased by a higher concentration of pyrophosphate. This biphasic effect of pyrophosphate on Pi binding was not observed with ADP, which, at all concentrations tested, inhibited Pi binding. Except for the effect of pyrophosphate on Pi binding to F1, for all the other effects, pyrophosphate mimicked ADP. It is suggested that pyrophosphate and ADP share the same binding site on F1 and that pyrophosphate interacts with the same amino acid residues as those interacting with the alpha and beta phosphate groups of ADP. PMID- 2888762 TI - Characterization of the human blood coagulation factor XII gene. Intron/exon gene organization and analysis of the 5'-flanking region. AB - A human genomic phage library was screened using a human factor XII cDNA as a hybridization probe. Two overlapping phage clones were isolated which contain the entire human factor XII gene. DNA sequence and restriction enzyme analysis of the clones indicate that the gene is approximately 12 kilobase pairs in size and is comprised of 13 introns and 14 exons. Exons 3-14 are contained in a genomic region of only 4.2 kilobase pairs with introns ranging in size from 80 to 554 base pairs. The coding sequence of factor XII consists of multiple putative domains that are homologous to putative domains found in fibronectin and tissue type plasminogen activator. These regions were found as separate exons in the gene. The intron/exon gene organization is similar to the serine protease gene family of plasminogen activators and not to the clotting factor family. Analysis of the 5' end of the gene shows that it does not contain the typical TATA and CAAT sequences found in other genes. This is consistent with the finding that transcription of the gene is initiated at multiple sites. PMID- 2888763 TI - Biosynthesis of heterogeneous forms of multidrug resistance-associated glycoproteins. AB - Multidrug-resistant J774.2 mouse macrophage-like cells, selected for resistance to colchicine, vinblastine, or taxol, overexpress antigenically related glycoproteins with distinct electrophoretic mobilities. These plasma membrane glycoproteins are likely to play a pivotal role in the expression of the multidrug resistance phenotype. To determine how these multidrug resistance associated glycoproteins differ, the biosynthesis and N-linked carbohydrate composition of these proteins were examined and compared. Vinblastineor colchicine-selected cells made a 125-kDa precursor that was rapidly processed (t1/2 approximately equal to 20 min) to mature forms of 135 and 140 kDa, respectively. Heterogeneity between the 135- and 140-kDa forms of the molecule can be attributed to N-linked carbohydrate. In contrast, taxol-selected cells made two precursors, 125 and 120 kDa, which appeared within 5 and 15 min after the onset of pulse labeling, respectively. They were processed to mature forms of 140 and 130 kDa. Since a single deglycosylated precursor or mature form was not observed after enzymatic removal of N-linked oligosaccharides, other differences, besides N-linked glycosylation, which occur in early processing compartments, are likely to account for the two multidrug resistance-associated glycoproteins in taxol-selected cells. These results demonstrate that a family of multidrug resistance-associated glycoproteins can be differentially expressed. PMID- 2888764 TI - Evidence for catalytic cooperativity during ATP hydrolysis by beef heart F1 ATPase. Kinetics and binding studies with the photoaffinity label BzATP. AB - The photoaffinity analog of ATP, 3'-O-(4-benzoyl) benzoyl ATP (BzATP), was used to covalently modify the catalytic sites on the beef heart mitochondrial F1 ATPase. In the absence of actinic illumination, BzATP was a slow substrate for the enzyme (Vmax = 0.19 mumol min-1 mg-1; kcat/Km = 2.2 X 10(6) M-1s-1) and behaved as a classical competitive inhibitor versus ATP (Ki = 0.85 microM). Under photolytic conditions, BzATP inactivated F1 with pseudo first-order kinetics, and the photoinactivation reaction showed rate saturation suggesting specific, reversible binding of BzATP to F1 prior to covalent bond formation. ATP protected against F1 photoinactivation (Kprotect = 0.3 microM) and partially covalently modified F1 yielded the same Km for ATP as unmodified enzyme. These results strongly suggested that BzATP was bound to catalytic sites on the enzyme. In the absence of photolysis, BzATP saturated two binding sites on the F1 (KD = 1.6 microM), and under photolytic conditions, 1 mol of BzATP was shown to be covalently liganded to the beta subunit of the enzyme coincident with 100% loss in ATPase activity. Previous studies with the mitochondrial F1-ATPase have suggested a mechanism involving catalytic cooperativity during ATP hydrolysis. Our demonstration of a molar stoichiometry of 1 for photoinactivation is in accord with this mechanism. It is suggested that either F1 is unable to hydrolyze covalently bound BzATP, or that subsequent to hydrolysis, the BzADP product can not be released from the catalytic site. It is therefore inferred that F1 hydrolytic activity requires cooperativity between multiple, viable catalytic sites and that covalent modification of a single catalytic site is sufficient for complete enzyme inactivation. PMID- 2888765 TI - Mechanisms for direct inhibition of canine gastric parietal cells by somatostatin. AB - To examine the potential mechanisms by which somatostatin inhibits gastric acid secretion we studied its effects on isolated canine gastric parietal cells. Using 125I-[Leu8-D-Trp22-Tyr25]somatostatin-28 as ligand, we identified somatostatin binding sites in parietal cell-enriched fractions of fundic mucosa. Two binding sites with respective dissociation constants of 3.2 X 10(-9) and 2.1 X 10(-7) M were identified. Somatostatin-14 and -28 were equally potent both in displacing bound ligand and in inhibiting parietal cell activity as measured by [14C]aminopyrine uptake. Pertussis toxin reversed the ability of somatostatin to inhibit the uptake of [14C]aminopyrine and production of cAMP by parietal cells stimulated with histamine and forskolin but not with dibutyryl cAMP or pentagastrin. Furthermore, somatostatin had no effect on parietal cell membrane inositol phospholipid turnover or changes in protein kinase C (Ca2+/phospholipid dependent enzyme) activity induced by carbachol or pentagastrin. These data indicate that somatostatin directly inhibits parietal cell activity via mechanisms both dependent on and independent of the pertussis toxin-sensitive inhibitory guanine nucleotide-binding protein. PMID- 2888766 TI - The sequence and expression of the divergent beta-tubulin in chicken erythrocytes. AB - We report here the complete sequence of a highly divergent chicken erythrocyte beta-tubulin, c beta 6, which appears to represent a major exception to the observation that the primary sequences and sites of expression of beta-tubulin isotypes are conserved within vertebrates. The amino acid sequence was deduced from overlapping cloned cDNAs identified in a chicken erythroblast cDNA library contained in the expression vector, lambda gt11. Compared with other chicken beta tubulins, among which the maximum sequence divergence is only 8%, c beta 6 tubulin is more hydrophobic, contains seven fewer net negative charges, and exhibits a surprising 17% overall divergence in its amino acid sequence. DNA and RNA blot analyses show that c beta 6-tubulin is present as a single gene copy in the chicken genome and is specifically expressed in the bone marrow. Comparisons of RNA blots and immunoblots of various cells and tissues confirm that this beta tubulin isotype is contained specifically in erythrocytes and thrombocytes and accounts for 75% of the beta-tubulin mRNA species contained in developing erythroblasts. Interestingly, c beta 6-tubulin exhibits 18% amino acid sequence divergence relative to MB1, the analogous hematopoietic beta-tubulin contained in mouse. PMID- 2888767 TI - Identification of dopamine receptor subtypes in the hypotensive action of SK&F 85174 in anesthetized rats. AB - 1 We have performed experiments to determine the effect of SK&F 85174 on blood pressure in anaesthetized rats and identify dopamine receptor subtype(s) involved in its action. 2 SK&F 85174 decreased blood pressure in a dose-related manner. There were no significant changes in heart rate. The hypotensive action was short lasting and was significantly antagonized by the selective DA1-receptor antagonist. SCH 23390 (100 micrograms/kg). This dose of SCH 23390 did not alter the hypotension produced by the DA2-receptor agonist, quinpirole. 3 The DA2 receptor antagonist, domperidone (25 micrograms/kg), did not significantly alter the hypotension produced by lower doses of SK&F 85174, but antagonized the hypotensive action of the highest dose of SK&F 85174 by about 35%. This dose of domperidone antagonized the hypotension produced by quinpirole by 85% without affecting the hypotensive action of the DA1-receptor agonist, fenoldopam. 4 These results show that at lower doses of SK&F 85174, the hypotension is due primarily to DA1-receptor activation, whereas DA2-receptor activation may also contribute to the blood pressure decrease produced by higher doses of SK&F 85174. PMID- 2888768 TI - The lack of the effect of DA-1 and DA-2 dopamine agonists on the isolated guinea pig atria. AB - 1 The effects of dopamine and both DA-1 and DA-2 dopamine receptor agonists have been studied on the contractile force of electrically driven guinea-pig left atria and frequency of spontaneously beating right atria. 2 Pretreatment of animals with reserpine caused a parallel rightward shift of the concentration response curve to dopamine of either preparation. 3 Propranolol, but not domperidone, shifted to the right the dose-response curve for the positive inotropic and chronotropic effects of dopamine. 4 Neither apomorphine, fenoldopam, bromocriptine nor piribedil had effects on the frequency and contractile force of the isolated guinea-pig atria. 5 These results suggest that DA-1 and DA-2 dopamine receptors are neither directly nor indirectly (prejunctional effect) involved in the inotropic and chronotropic effects of dopamine in isolated guinea-pig atria. PMID- 2888769 TI - Magnetic resonance imaging in pediatric vascular disease. AB - Magnetic resonance imaging (MRI) was used to study eight children with known vascular disease proved by angiography. Congenital and acquired large vessel disease was equally well demonstrated noninvasively by both MRI and angiography, and in one patient MRI provided superior information about pulmonary artery patency. PMID- 2888770 TI - Acquisition of antigens characteristic of adult pericentral hepatocytes by differentiating fetal hepatoblasts in vitro. AB - Antigens specific to pericentral hepatocytes have been studied in adult mouse liver, during fetal development, and in cultured fetal hepatoblasts. Antibody reactive with glutamine synthetase stained all fetal liver cells but almost all cells lost this antigen after birth; only a single layer of pericentral cells retained it in adulthood. In contrast, monoclonal antibodies to major urinary protein (MUP) did not detect the antigen until approximately 3 wk after birth, after which time the cells within 6-10 cell diameters of the central veins were positive. Cultured fetal liver cells from embryos at 13 +/- 1 d of gestation were capable of differentiating in vitro to mimic events that would occur had the cells remained in the animal. About 10-20% of the explanted cells grew into clusters of hepatocyte-like cells, all of which stained with albumin antibodies. MUP monoclonals were reactive with one-half of the differentiated fetal hepatocytes. Glutamine synthetase was present in all hepatocytes after several days in culture and gradually decreased and remained in only occasional cells, all of which also contained the MUP antigen. These findings suggest that a sequence of gene controls characterizes expression of specific genes in developing liver, and that differentiating fetal hepatoblasts are capable of undergoing similar patterns of gene activity in culture. PMID- 2888771 TI - Control of microtubule nucleation and stability in Madin-Darby canine kidney cells: the occurrence of noncentrosomal, stable detyrosinated microtubules. AB - The microtubule-nucleating activity of centrosomes was analyzed in fibroblastic (Vero) and in epithelial cells (PtK2, Madin-Darby canine kidney [MDCK]) by double immunofluorescence labeling with anti-centrosome and antitubulin antibodies. Most of the microtubules emanated from the centrosomes in Vero cells, whereas the microtubule network of MDCK cells appeared to be noncentrosome nucleated and randomly organized. The pattern of microtubule organization in PtK2 cells was intermediate to the patterns observed in the typical fibroblastic and epithelial cells. The two centriole cylinders were tightly associated and located close to the nucleus in Vero and PtK2 cells. In MDCK cells, however, they were clearly separated and electron microscopy revealed that they nucleated only a few microtubules. The stability of centrosomal and noncentrosomal microtubules was examined by treatment of these different cell lines with various concentrations of nocodazole. 1.6 microM nocodazole induced an almost complete depolymerization of microtubules in Vero cells; some centrosome nucleated microtubules remained in PtK2 cells, while many noncentrosomal microtubules resisted that treatment in MDCK cells. Centrosomal and noncentrosomal microtubules regrew in MDCK cells with similar kinetics after release from complete disassembly by high concentrations of nocodazole (33 microM). During regrowth, centrosomal microtubules became resistant to 1.6 microM nocodazole before the noncentrosomal ones, although the latter eventually predominate. We suggest that in MDCK cells, microtubules grow and shrink as proposed by the dynamic instability model but the presence of factors prevents them from complete depolymerization. This creates seeds for reelongation that compete with nucleation off the centrosome. By using specific antibodies, we have shown that the abundant subset of nocodazole-resistant microtubules in MDCK cells contained detyrosinated alpha-tubulin (glu tubulin). On the other hand, the first microtubules to regrow after nocodazole removal contained only tyrosinated tubulin. Glu-tubulin became detectable only after 30 min of microtubule regrowth. This strongly supports the hypothesis that alpha tubulin detyrosination occurs primarily on "long lived" microtubules and is not the cause of the stabilization process. This is also supported by the increased amount of glu-tubulin that we found in taxol-treated cells. PMID- 2888772 TI - Lysyl oxidase activity and elastin/glycosaminoglycan interactions in growing chick and rat aortas. AB - Hydrophobic tropoelastin molecules aggregate in vitro in physiological conditions and form fibers very similar to natural ones (Bressan, G. M., I. Pasquali Ronchetti, C. Fornieri, F. Mattioli, I. Castellani, and D. Volpin, 1986, J. Ultrastruct. Molec. Struct. Res., 94:209-216). Similar hydrophobic interactions might be operative in in vivo fibrogenesis. Data are presented suggesting that matrix glycosaminoglycans (GAGs) prevent spontaneous tropoelastin aggregation in vivo, at least up to the deamination of lysine residues on tropoelastin by matrix lysyl oxidase. Lysyl oxidase inhibitors beta-aminopropionitrile, aminoacetonitrile, semicarbazide, and isonicotinic acid hydrazide were given to newborn chicks, to chick embryos, and to newborn rats, and the ultrastructural alterations of the aortic elastic fibers were analyzed and compared with the extent of the enzyme inhibition. When inhibition was greater than 65% all chemicals induced alterations of elastic fibers in the form of lateral aggregates of elastin, which were always permeated by cytochemically and immunologically recognizable GAGs. The number and size of the abnormal elastin/GAGs aggregates were proportional to the extent of lysyl oxidase inhibition. The phenomenon was independent of the animal species. All data suggest that, upon inhibition of lysyl oxidase, matrix GAGs remain among elastin molecules during fibrogenesis by binding to positively charged amino groups on elastin. Newly synthesized and secreted tropoelastin has the highest number of free epsilon amino groups, and, therefore, the highest capability of binding to GAGs. These polyanions, by virtue of their great hydration and dispersing power, could prevent random spontaneous aggregation of hydrophobic tropoelastin in the extracellular space. PMID- 2888773 TI - Pathways of glutamine and glutamate metabolism in resting and proliferating rat thymocytes: comparison between free and peptide-bound glutamine. AB - Pathways of glutamine metabolism in resting and proliferating rat thymocytes were evaluated by in vitro incubations of freshly prepared or 60-h cultured cells for 1-2 h with [U14C]glutamine. Complete recovery of glutamine carbons utilized in products allowed quantification of the pathways of glutamine metabolism under the experimental conditions. Partial oxidation of glutamine via 2-oxoglutarate in a truncated citric acid cycle to CO2 and oxaloacetate, which then was converted to aspartate, accounted for 76 and 69%, respectively, of the glutamine metabolized beyond the stage of glutamate by resting and proliferating thymocytes. Complete oxidation to CO2 in the citric acid cycle via 2-oxoglutarate dehydrogenase and isocitrate dehydrogenase accounted for 25 and 7%, respectively. In proliferating cells a substantial amount of glutamine carbons was also recovered in pyruvate, alanine, and especially lactate. The main route of glutamine and glutamate entrance into the citric acid cycle via 2-oxoglutarate in both cells is transamination by aspartate aminotransferase rather than oxidative deamination by glutamate dehydrogenase. In the presence of glucose as second substrate, glutamine utilization and aspartate formation markedly decreased, but complete oxidation of glutamine carbons to CO2 increased to 37 and 23%, respectively, in resting and proliferating cells. The dipeptide, glycyl-L-glutamine, which is more stable than free glutamine, can substitute for glutamine in thymocyte cultures at higher concentrations. PMID- 2888774 TI - Coated vesicles and protein sorting. PMID- 2888775 TI - Isolation of an endocytic compartment from A431 cells using a density modification procedure employing a receptor-specific monoclonal antibody complexed with colloidal gold. AB - Our objective was to isolate a prelysosomal compartment involved in receptor mediated endocytosis in human epidermoid carcinoma (A431) cells. The isolation protocol involves density modification of endosome elements in A431 cells, caused by the receptor-dependent binding and internalization at 20 degrees C of colloidal gold-transferrin receptor antibody (B3/25) particles. The use of 125I labelled gold-B3/25 provides a radioactive marker for the endosome compartment, the major peak being recovered at the bottom of a continuous sucrose gradient at a density of 1.23g ml-1. Enzyme markers characteristic of other cytoplasmic compartments are present only in negligible amounts in this fraction and L [35S]methionine-labelling of the cells indicates approximately a 200-fold enrichment of 125I-labelled gold-B3/25 versus protein. Electron microscopy of the endosome-rich fraction reveals that we have isolated a highly purified population of small gold-containing vesicles and tubules from which the transferrin receptor can be immunoprecipitated using the B3/25 antibody. Gel electrophoresis and fluorography of L-[35S]-methionine-labelled cells suggests that these elements contain a characteristic profile of approximately 10 major proteins of which three appear to be specifically enriched. In cells incubated with [125I]transferrin, 12% of the ligand sediments with the gold-labelled elements. We conclude, therefore, that the components we have isolated play a role in the intracellular processing of the transferrin-transferrin receptor complexes. PMID- 2888776 TI - Enhancement of pheomelanogenesis by L-dopa in the mouse melanocyte cell line, TM10, in vitro. AB - Cells of TM10, an established cell line, are melanocytes that contain equal amounts of eumelanin (black pigment) and pheomelanin (yellow pigment). The content of pheomelanin drastically increased when the cells were cultured in growth medium containing 0.2mM-L-dopa (L-dihydroxyphenylalanine), which is the common precursor for both eumelanogenesis and pheomelanogenesis. After this treatment, the amount of pheomelanin was 3.7-fold greater than that of control in TM10, whereas the amount of eumelanin changed very little. In contrast, 5-S cysteinyl-dopa, which is the specific precursor for pheomelanogenesis downstream of L-dopa, did not cause preferential increase in pheomelanogenesis. Ultrastructural observations also confirmed these results; in 0.2mM-L-dopa, an increase in the number of pheomelanosomes was observed in the cytoplasm of TM10 cells. Our results also suggest that the L-dopa treatment results in a decrease in tyrosinase activity per melanosome. PMID- 2888777 TI - Vasomotor effects of neurotransmitters and modulators on isolated human pial veins. AB - Vasomotor reactivity of human pial veins, obtained in conjunction with neurosurgical operations, was studied in vitro. The effect of transmitters in nerves previously recognized in these vessels, as well as that of neuromodulators, was characterized. A comparison of these effects with their effects in the nearby pial arteries of the same patients was made. It was found that the veins were equipped with more sensitive alpha-adrenergic receptors (lower EC50 values) than the arteries. The reverse was found for 5 hydroxytryptamine. Acetylcholine, which causes an endothelium-dependent dilation of pial arteries, contracted the veins despite an apparently intact endothelium. Considering the lower maximum values in veins, responses to histamine, the neuropeptides calcitonin gene-related peptide, bradykinin, and neuropeptide Y; and prostaglandins (PGE1 and PGF2 alpha) were principally the same in the arteries and veins. The dilatory responses to vasoactive intestinal polypeptide and substance P were less pronounced in veins than in arteries. The veins only transiently contracted to a depolarizing potassium solution; calcium influx promotors and inhibitors, as well as calcium-free solution, did not affect the contractile ability of the vein, contrasting to the reactivity of the artery. This clearly indicates that the veins are not substantially dependent upon calcium influx for their acute contractile ability. PMID- 2888778 TI - Pharmacological treatment of cancer pain. PMID- 2888779 TI - Determination of isofloxythepin in biological fluids by gas chromatography-mass spectrometry. AB - A method for the determination of isofloxythepin in biological fluids by gas chromatography-mass spectrometry is described. Isofloxythepin was readily converted into the trimethylsilyl ether by treatment with N,O bis(trimethylsilyl)trifluoroacetamide. This derivative was separated on a 5% OV 101 column and determined, employing newly prepared isofloxythepin-d7 as an internal standard. Clean-up of isofloxythepin in blood and urine was efficiently achieved by back-extraction with hexane or hexane-toluene (9:1) under acidic and basic conditions, while isofloxythepin glucuronide in biological fluids was isolated by ion-exchange chromatography on Dowex 50W-X4 resin. The detection limit of isofloxythepin by this method was 50 pg. The blood and urine levels of isofloxythepin after oral administration of the drug to dogs were monitored by the proposed method. PMID- 2888780 TI - Determination of the agonist-antagonist anxiolytic agent 6-(2-chlorophenyl)-4 hydroxy-4H-imidazo[1,5-a]-[1,4]benzodiazepine- 3-carboxamide and its benzophenone carboxylic acid metabolite in plasma by high-performance liquid chromatography. AB - A rapid, sensitive and selective high-performance liquid chromatographic (HPLC) assay was developed for the determination of 6-(2-chlorophenyl)-4-hydroxy-4H imidazo[1,5-a]-[1,4]benzodiazepine- 3-carboxamide (I) and its benzophenone carboxylic acid metabolite, 1-[2-(2-chlorobenzoyl)phenyl]-4-(aminocarbonyl)-1H imidazole-5-car boxylic acid (II) in plasma. The assay involves the extraction of both compounds into benzene from buffered plasma (pH 5.4) and subsequent analysis by reversed-phase HPLC. The overall recovery of I and II is 98.3 +/- 9.4 and 59.7 +/- 15.7% for dog plasma, 86.0 +/- 14.7 and 52.8 +/- 15.1% for rat plasma and 98.1 +/- 9.3 and 66.9 +/- 18.0% for human plasma, respectively. The sensitivity limit of the assay for I and II is 20.0 and 40.0 ng/ml of plasma using ultraviolet detection at 254 nm. The assay was used in studies in dog and rat. PMID- 2888781 TI - Automated pre-column derivatization with o-phthalaldehyde for the determination of neurotransmitter amino acids using reversed-phase liquid chromatography. PMID- 2888782 TI - Free fatty acids block growth hormone (GH) releasing hormone-stimulated GH secretion in man directly at the pituitary. AB - Increases in plasma FFA levels inhibit GH responses to a variety of pharmacological and physiological stimuli. To gain further insight into the mechanism by which FFA exert their effect, we studied the plasma GH responses to GHRH-(1-44) (1 microgram/kg, iv) in normal subjects in whom plasma FFA levels were raised by a lipid-heparin infusion (250 mL 10% Intralipid plus 2500 U heparin). Paired tests were performed in 10 normal subjects, with and without lipid-heparin pretreatment. Lipid-heparin infusion from -30 to 120 min increased mean FFA levels from 0.41 +/- 0.03 (+/- SEM) to 3.12 +/- 0.40 mmol/L at 120 min. The mean plasma GH levels after GHRH administration were lower at all times; however, the values were significantly different (P less than 0.05) only at the later times (45, 60, and 90 min). When considered individually, an all or none pattern was observed; 5 subjects had no plasma GH response to GHRH, and 5 had no reduction. To investigate the time relationships between the FFA peak and subsequent GH blockade, a different protocol of paired tests was performed with GHRH with or without a different lipid-heparin infusion protocol. Lipid-heparin was infused from -90 to 0 min, with an additional heparin pulse at -15 min, to obtain a higher and earlier (0 min) FFA increase. FFA increased from 1.06 +/- 0.19 to 11.61 +/- 0.83 mmol/L at zero time. The GHRH-induced GH secretory peak (15.8 +/- 3.5 ng/ml) at 15 min was completely blocked (0.9 +/- 0.2 ng/ml), and the mean plasma GH levels were also lower at 30, 45, and 60 min. To determine whether the FFA-induced blockade of GH secretion was exerted in the pituitary, a series of in vitro studies was conducted using monolayer cultures of rat anterior pituitary glands, with GHRH concentrations of both 10(-10) and 10(-8) M and 10( 5) M forskolin to stimulate GH release. Both caprylic and oleic acid inhibited basal GH release and GHRH- or forskolin-induced GH release. PRL release was not altered, nor were toxic actions noted on the cells. In conclusion, FFA are able to block GH secretion directly at the pituitary level. PMID- 2888783 TI - Polymorphism of the T cell receptor beta-chain in Graves' disease. AB - We investigated the T cell antigen receptor constant (TCR beta) beta-chain genes of patients with Graves' disease using restriction fragment length polymorphism analysis. Genomic DNA from patients and normal subjects was digested with the restriction endonuclease Bg1 II, transferred to nylon membranes using the Southern blot technique, and hybridized with a TCR beta probe. A significant increase in the frequency of the 10.0; 9.2-kilobase heterozygous phenotype was found in GD (68.6%) vs. 42.1% in normal subjects (P = 0.003). Using the complex phenotype TCR homozygote (hetero) DR3 as a reference (odds ratio = 1.00), we found that the risk for Graves' disease was restricted to TCR beta heterozygote/DR3+ individuals (odds ratio = 8.31; chi 2 = 11.82; P = 0.0009); in the absence of TCR beta heterozygosity, DR3 was not significantly associated with the disease. These results suggest that TCR beta chain genes also are associated with susceptibility to GD and that the association is most pronounced in (or restricted to) those individuals who are HLA DR3 positive. PMID- 2888784 TI - Toxic multinodular goiter: a variant of autoimmune hyperthyroidism. AB - The aim of this study was to examine whether at least a subgroup of patients with toxic multinodular goiter may have autoimmune thyroid disease. Thyroid stimulating immunoglobulin (TSI) activity, measured by a sensitive bioassay employing cultured human thyroid cells, was determined in patients with toxic multinodular goiter and other thyroid disorders. All patients with active Graves' disease (n = 47) had detectable serum TSI activity, whereas TSI was undetectable in patients with thyroid disease not believed to be of autoimmune origin: toxic adenoma (n = 13), cold nodule (n = 5), and nontoxic goiter (n = 19), with a single exception in the latter group. Toxic multinodular goiter (n = 26) was diagnosed based on clinical and laboratory evidence of hyperthyroidism associated with a multinodular goiter on palpation and scintiscan. The toxic multinodular goiter group was then subclassified according to scintiscan pattern (type A, diffuse but uneven distribution of technetium uptake; type B, multiple discrete nodules of varying size and function). All but 1 of the 11 TSI-positive toxic multinodular goiter patients had a type A scintiscan pattern. The patients with the type A scintiscan pattern were younger and more often had elevated antithyroid antibody titers, ophthalmopathy, and concurrent development of goiter and hyperthyroidism (rather than long-standing goiter preceding hyperthyroidism) compared to the type B patients. Thus, a subgroup of patients with clinically defined toxic multinodular goiter (type A) probably have autoimmune hyperthyroidism (a variant of Graves' disease), while in another subgroup (type B) hyperthyroidism is not related to an autoimmune etiology (a variant of toxic adenoma). PMID- 2888785 TI - SMS 201-995 induces a continuous decline in circulating growth hormone and somatomedin-C levels during therapy of acromegalic patients for over two years. AB - Ten acromegalic patients, four previously untreated, were studied before and at regular intervals during treatment with the long-acting somatostatin analog SMS 201-995 (200-300 micrograms daily for 2 or 3 sc injections for 16-108 weeks). All patients had rapid clinical improvement, with disappearance of excessive perspiration, paresthesias, and headache within the first 6 weeks of therapy. The mean 24-h serum GH concentrations fell from 44.0 +/- 7.8 (+/-SE) micrograms/L before to 5.9 +/- 1.0 microgram/L at the end of therapy. The GH levels from 2-6 h after the acute administration of 50 micrograms SMS 201-995 before the start of therapy correlated significantly with the mean 24-h GH concentrations after 16 108 weeks of treatment (P less than 0.05). The initially increased serum somatomedin-C (Sm-C) levels normalized in 5 of these 10 patients; the mean values were 7.3 +/- 0.9 U/mL before and 2.9 +/- 0.7 U/mL at the end of therapy. The Sm-C and mean GH levels continuously decreased during long term therapy; the concentrations after 1.5-2 yr of therapy were significantly lower than those after 6-12 months of therapy (P less than 0.01 and P less than 0.01, respectively). A slight decrease in the size of the pituitary tumor was noted by computed tomography in three of six patients. Transient clinically detectable steatorrhea occurred in two patients. Postprandial hyperglycemia occurred during therapy in eight patients, while in two patients with type 2 diabetes mellitus carbohydrate tolerance improved in one and deteriorated in the other. SMS 201-995 is a highly effective medical treatment for acromegaly. Clinically improvement occurs rapidly, and the inhibition of serum GH and Sm-C levels persisted even after more than 1 yr of therapy. No important subjective side-effects were noted. SMS 201-995 is an excellent drug in patients in whom acromegaly persists after surgery and for interim treatment to shorten the period of clinical activity after irradiation. PMID- 2888786 TI - Human homoeobox-containing genes in development. AB - The homoeobox is a 183-bp DNA sequence conserved in several Drosophila genes controlling segmentation and segment identity. Homoeobox sequences have been detected in the genome of species ranging from insects and annelids to vertebrates, and homoeobox-containing genes have been cloned from sea urchin, Xenopus, mouse and man. We have recently isolated human homoeobox-containing complementary DNA clones which represent transcripts from four different human genes. We have studied the expression of these genes in tissues of human embryos and fetuses at 5-10 weeks post-conception. Most of them appear to be expressed in a stage- and tissue-specific pattern. We report here on the genomic organization of a number of human homoeoboxes and their transcriptional organization in human placenta. PMID- 2888787 TI - Apical Na+/H+ antiporter and glycolysis-dependent H+-ATPase regulate intracellular pH in the rabbit S3 proximal tubule. AB - The apical transport processes responsible for proton secretion were studied in the isolated perfused rabbit S3 proximal tubule. Intracellular pH (pHi) was measured with the pH dye, 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein. Steady state pHi in S3 tubules in nominally HCO3(-)-free solutions was 7.08 +/- 0.03. Removal of Na+ (lumen) caused a decrease in pHi of 0.34 +/- 0.06 pH/min. The decrease in pHi was inhibited 62% by 1 mM amiloride (lumen) and was unaffected by 50 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (lumen) and Cl- removal (lumen, bath). After a brief exposure to 20 mM NH4Cl, pHi fell by approximately 0.7 and recovered at a rate of 0.89 +/- 0.15 pH/min in the nominal absence of Na+, HCO3-, organic anions, and SO4(2-) (lumen, bath). 1 mM N,N' dicyclohexylcarbodiimide (lumen), 1 mM N-ethylmaleimide (lumen), 0.5 mM colchicine (bath), and 0.5 mM iodoacetic acid (lumen, bath) inhibited the Na+ independent pHi recovery rate by 73%, 55%, 77%, and 86%, respectively, whereas 1 mM KCN (lumen, bath) did not inhibit pHi recovery. Reduction of intracellular, but not extracellular chloride, also decreased the Na+-independent pHi recovery rate. In conclusion, the S3 proximal tubule has an apical Na+/H+ antiporter with a Michaelis constant for Na+ of 29 mM and a maximum velocity of 0.47 pH/min. S3 tubules also possess a plasma membrane H+-ATPase that can regulate pHi, has a requirement for intracellular chloride, and utilizes ATP derived primarily from glycolysis. PMID- 2888788 TI - Role of the Na+/H+ antiporter in rat proximal tubule bicarbonate absorption. AB - Amiloride and the more potent amiloride analog, 5-(N-t-butyl) amiloride (t butylamiloride), were used to examine the role of the Na+/H+ antiporter in bicarbonate absorption in the in vivo microperfused rat proximal convoluted tubule. Bicarbonate absorption was inhibited 29, 46, and 47% by 0.9 mM or 4.3 mM amiloride, or 1 mM t-butylamiloride, respectively. Sensitivity of the Na+/H+ antiporter to these compounds in vivo was examined using fluorescent measurements of intracellular pH with (2', 7')-bis(carboxyethyl)-(5,6)-carboxyfluorescein (BCECF). Amiloride and t-butylamiloride were shown to be as potent against the antiporter in vivo as in brush border membrane vesicles. A model of proximal tubule bicarbonate absorption was used to correct for changes in the luminal profiles for pH and inhibitor concentration, and for changes in luminal flow rate in the various series. We conclude that the majority of apical membrane proton secretion involved in transepithelial bicarbonate absorption is mediated by the Na+-dependent, amiloride-sensitive Na+H+ antiporter. However, a second mechanism of proton secretion contributes significantly to bicarbonate absorption. This mechanism is Na+-independent and amiloride-insensitive. PMID- 2888789 TI - Bevantolol: a beta-1 adrenoceptor antagonist with unique additional actions. AB - Bevantolol is a beta-1 adrenoceptor antagonist that has been shown to be as effective as other beta blockers for the treatment of angina pectoris and hypertension. Some interesting additional properties, such as the absence of the side effect of cold extremities, required investigation, and a great deal of new evidence has been accumulated during the last three years. This new data is consistent with the proposal put forward a couple of years ago that bevantolol interacts with alpha-adrenoceptors. All the available evidence, published and unpublished, has been reviewed and fits into a coherent pattern, here arranged into five sections. Chemistry: affinity for alpha-adrenoceptors. Animal experiments confirm both agonist and antagonist effects on alpha-receptors, in addition to antagonist activity at beta-1 receptors. In addition, bevantolol has electrophysiologic effects, including bradycardia by a direct action on the sinus node and a class 1 antiarrhythmic action. Investigations in humans have shown that although bevantolol has a short half-life, good control of hypertension can be achieved on once-a-day dosing. SAFETY: bevantolol has remarkably few side effects, does not cause cold extremities, and does not significantly affect glomerular filtration rate in patients with renal impairment. Evidence has been obtained in man for interaction with alpha-adrenoceptors in the brain; and in the peripheral circulation bevantolol does not, as do other beta blockers, increase peripheral vascular resistance, but reduces it. It is suggested that all the additional actions of bevantolol can be attributed to a partial agonist action on alpha-adrenoceptors. PMID- 2888790 TI - Short-term effects of beta blockers atenolol, nadolol, pindolol, and propranolol on lipoprotein metabolism in normolipemic subjects. AB - The short-term effect of the blockade of the beta-adrenergic receptors on serum lipoproteins and the plasma activities of the enzymes involved in the metabolism of the serum lipoproteins: lipoprotein lipase (LPL), hepatic lipase (HL) and lecithin: cholesterol acyltransferase (LCAT) was evaluated in ten healthy normolipemic and normotensive subjects. In the first part of the study, the first three-day period of placebo was followed by another three-day period during which propranolol (120 mg/d) was given. In the second, third, and fourth part of the study, the same schedule was used but pindolol (15 mg/d), nadolol (160 mg/d), atenolol (100 mg/d) were given respectively instead of propranolol. The four drugs induced a significant blockade of the beta-adrenergic receptors as evaluated by the measurement of the double two-step test of Master (-45%). Despite similar blockade, the effect on serum lipid concentrations depended on the type of drug: propranolol induced an increase in triglycerides and apoprotein B-concentrations and a decrease in serum high density lipoprotein cholesterol (HDL-C) and apoprotein AI-concentrations. Pindolol provoked only a slight decrease of serum HDL-C concentration. Nadolol and atenolol elicited a lowering of the same magnitude in HDL-C. Except for a possible slight increase in plasma LCAT activity on propranolol, there was no significant change in the plasma activities of LPL, HL, and LCAT during the blockade of the beta-adrenergic receptors with the drugs used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888791 TI - The effects of a beta-2 selective adrenergic agonist and a beta-nonselective antagonist on theophylline clearance. AB - Beta-adrenergic agonists and antagonists have been shown to alter theophylline pharmacokinetics. It was the purpose of this study to characterize further the effects that terbutaline and propranolol have on theophylline disposition. In nine healthy male volunteers, mean parameters for theophylline disposition did not change after four days of terbutaline (5 mg q8h). Theophylline clearance, however, did change within the subjects. Clearance increased in five subjects, decreased in three, and remained unchanged in one volunteer. Pretreatment with four days of terbutaline (5 mg q8h) and propranolol (60 mg q8h) significantly decreased mean theophylline clearance (60.1 +/- 12.9 vs 40.6 +/- 9.9 mL/min/1.73m2; P less than .01) increased half-life (8.37 +/- 1.77 vs 12.32 +/- 2.70 hours; P less than .05), and increased postinfusion theophylline concentration (13.5 +/- 2.7 vs 18.95 +/- 2.5 micrograms/mL; P less than .001). In five subjects theophylline clearance increased after terbutaline pretreatment (64.6 +/- 13.0 vs 75.0 +/- 13.9 mL/min/1.73m2). The percentage increase ranged from 3.9 to 28.5%. These subjects were restudied after receiving propranolol alone (60 mg q8h). Comparison between the propranolol and terbutaline study and the propranolol alone study indicated no mean change in clearance in these five subjects (41.8 +/- 12.7 vs 36.1 +/- 5.1 mL/min/1.73m2). Thus it appears that the changes observed in these five subjects after terbutaline pretreatment may have been random in occurrence as has been shown to occur with theophylline disposition and are not related to terbutaline pretreatment. It is concluded that beta-2 adrenergic stimulation does not alter theophylline pharmacokinetics, whereas nonselective beta-adrenergic antagonism profoundly affected theophylline disposition. This is an additional reason not to use propranolol in patients who receive theophylline. PMID- 2888792 TI - Esmolol-digoxin drug interaction. AB - An open-label baseline-controlled study was conducted in 11 healthy male subjects to study the possible interaction between the cardioselective, short-acting beta blocker esmolol and digoxin when administered concurrently under steady-state conditions. Steady-state concentration, elimination half-life, and the total body clearance of esmolol were not changed significantly (P greater than .05) by digoxin. Digoxin peak concentration and the time to reach the peak concentration were not affected by esmolol. However, the digoxin AUC during the six-hour esmolol infusion increased from 2.60 +/- 0.59 to 2.88 +/- 0.75 ng.hr/mL (P less than .05). There were no clinically significant changes in the heart rate and blood pressure during this drug interaction study. The PR intervals were similar between digoxin monotherapy and esmolol plus digoxin combined treatment. Although digoxin did not influence the kinetics of esmolol, the small increase seen in digoxin serum concentration during the combination therapy warrants that caution be exercised during concurrent administration of esmolol and digoxin to patients. PMID- 2888793 TI - Hemodynamic effects of esmolol, an ultrashort-acting beta blocker. AB - The hemodynamic effects of esmolol were evaluated in 12 male patients at rest (mean age, 51 +/- 10 years) undergoing routine cardiac catheterization. Hemodynamic measurements were obtained during baseline (prior to esmolol), at steady state (during an intravenous infusion of esmolol 300 micrograms/kg/min), and at 30 minutes after stopping esmolol (postinfusion). Esmolol produced hemodynamic effects similar to the effects of other beta blockers. Significant reductions in rate-pressure product (mean decrease, 15%), cardiac index (mean decrease, 17%), stroke volume index (mean decrease, 13%), left ventricular stroke work index (mean decrease, 20%), and left ventricular ejection fraction (mean decrease, 18%) were observed. In contrast to other beta blockers, all hemodynamic effects of esmolol had returned to baseline values within 30 minutes after the infusion stopped. One patient exhibited hypotension during the esmolol infusion; this episode resolved without sequelae after discontinuation of esmolol. In summary, the effects of esmolol at rest on hemodynamic parameters and left ventricular function are similar to other beta-adrenergic blocking agents. Due to its ultrashort half-life, esmolol can be administered safely in critically ill patients whose disease status makes treatment with currently available beta blockers risky. PMID- 2888794 TI - The effect of beta blockers on cardiac neural discharge associated with coronary occlusion in the cat. AB - The effect of timolol on postganglionic cardiac sympathetic neural discharge, blood pressure, heart rate, and rhythm changes associated with acute coronary occlusion of the left anterior descending artery was examined and compared with the effects of the beta blockers practolol and metoprolol. Timolol (5 mg/kg, IV) was infused 15 minutes prior to coronary occlusion in cats anesthetized with alpha-chloralose. Control heart rate fell from 129 +/- 10 to 106 +/- 2 one minute prior to coronary occlusion and remained at 106 +/- 2 beats/minute in the minute prior to arrhythmia. Control blood pressure fell from 126 +/- 20 to 91 +/- 19 and stabilized at 99 +/- 19 mm Hg one minute prior to coronary occlusion. Mean time to arrhythmia and death was 4.7 +/- 2.3 and 68.0 +/- 51.0 minutes (P greater than .05 vs no drug), respectively. Three cats died and two were sacrificed six hours after coronary occlusion. Blood pressure fell to 86 +/- 20 mm Hg two minutes after coronary occlusion, rose to 95 +/- 23 mm Hg at ten minutes, and remained there for ten minutes. Timolol did not alter postganglionic cardiac sympathetic neural discharge prior to coronary occlusion. Two minutes after coronary occlusion, mean postganglionic cardiac sympathetic neural discharge was 128 +/- 27 and increased to 139 +/- 36 impulses/second (% control) 4 minutes after coronary occlusion. A similar trend was found for the data recorded in 15 nerves (eight cats) in which coronary occlusion was initiated without timolol. The data suggest that a difference exists among beta blockers because prior to coronary occlusion, the cardioselective drugs metoprolol (1, 5, and 10 mg/kg, IV) and practolol (8 mg/kg, IV) depressed postganglionic cardiac sympathetic neural discharge whereas noncardioselective timolol did not. Because all three beta blockers increased the times to arrhythmia and death (although the increase was significant only after metoprolol and practolol), the acute protective mechanism does not appear to be due primarily to a depression of spontaneous sympathetic neural discharge. PMID- 2888795 TI - Effects of celiprolol on systemic and forearm circulation in hypertensive patients: a double-blind cross-over study versus metoprolol. AB - The antihypertensive efficacy of a new beta-receptor blocking agent, celiprolol, was compared with that of a well-established antihypertensive drug, metoprolol. Their systemic and forearm hemodynamic effects were investigated using echocardiography and two-dimensional pulsed Doppler flowmetry, respectively. Twenty hypertensive patients completed a double-blind, cross-over, randomized study using celiprolol and metoprolol. Two six-week courses with celiprolol or metoprolol were preceded and followed by a two-week placebo period; the total duration of the study was 18 weeks. In spite of a comparable efficacy in reducing systolic and diastolic blood pressure (about 10% of the basal value), the two drugs showed quite different systemic and regional hemodynamic effects. Celiprolol induced a significant decrease in forearm vascular resistance (from 157 +/- 17 to 113 +/- 13 mm Hg/mL/s, P less than .01) and total peripheral resistance (from 1596 +/- 90 to 1398 +/- 91 dyne.s.cm-5, P less than .05) whereas cardiac output remained unchanged and forearm blood flow increased. Metoprolol reduced cardiac output (from 6.5 +/- 3 to 5.7 +/- 3 L/min, P less than .05), through a reduction in heart rate, since stroke volume was unchanged. Both drugs did not significantly modify cardiac performance, as evaluated by left ventricle fractional shortening and ejection fraction. Thus, the two drugs seem to reduce blood pressure through different hemodynamic mechanisms. PMID- 2888796 TI - Nizatidine, and H2-receptor antagonist: disposition and safety in the elderly. AB - Nizatidine is an orally active H2-receptor blocker. Its disposition and safety in eight young and 12 elderly volunteers were investigated. Single oral doses of nizatidine were administered: from 100 mg to 300 mg in the elderly, and from 100 mg to 350 mg in the young. The nizatidine AUC was directly proportional to dose for both groups. Calculated pharmacokinetic variables in the elderly vs. the young were t1/2 = 1.9 vs. 1.6 hr; CLp/f = 32 vs. 40 L/hr, and Vd beta/f = 1.2 vs. 1.3 L/kg. The impaired renal function of some elderly volunteers prolonged nizatidine elimination and lowered its clearance. Renal impairment rather than advanced age per se was the predominant factor in decreasing the nizatidine elimination rate. Because Clcr correlated directly with nizatidine renal clearance, Clcr values may be used to estimate nizatidine dosage reductions in renal insufficiency. During the trial, no serious adverse effects occurred. PMID- 2888797 TI - MR imaging of the adrenal gland in Sipple disease. AB - We assessed imaging techniques [nuclear, CT, and magnetic resonance (MR)] in the diagnosis of pheochromocytomas in 10 patients with Sipple disease. Nine patients underwent surgery. Magnetic resonance detected all adrenal and ectopic lesions. Metaiodobenzylguanidine scans had two false-negative results. Computed tomography missed an ectopic lesion that was associated with bilateral medullar hypertrophy and had a false-positive result (a cortical nonhyperfunctioning adenoma). In our opinion MR may replace both CT and nuclear scans in the work up of Sipple disease. PMID- 2888798 TI - Development of memory-enhancing agents in the treatment of Alzheimer's disease. PMID- 2888799 TI - The effect of fatty acid infusion on growth hormone secretion in the ovine fetus: evidence for immaturity of pituitary responsiveness in utero. AB - The fetal growth hormone response to a 2-h intravenous infusion of a free fatty acid emulsion, Intralipid, was studied in the late gestation ovine fetus. Fetuses received low, medium or high dose Intralipid infusions for 2 h. Low dose infusions (0.5-0.7 ml/kg, n = 3) produced no significant changes in growth hormone concentrations. Both medium (2.0-4.0 ml/kg, n = 6) and high (4.1-6.0 ml/kg, n = 4) dose infusions elicited a significant decrease (P less than 0.01) in fetal growth hormone concentrations. At the high dose, growth hormone concentrations comparable to those seen in newborn lambs (28.5 +/- 10.6 ng/ml), were observed. Such an inhibition of growth hormone has not previously been seen in fetuses. To determine the possible mechanism of this effect, studies of the fetal growth hormone response to growth hormone releasing factor and somatostatin in the presence of Intralipid were undertaken. During control studies with growth hormone releasing factor alone, there was a significant (P less than 0.05) increase in fetal growth hormone levels within 20 min of administering the growth hormone releasing factor bolus (0.1 microgram/kg, n = 5). Intralipid infusion (2.0-4.0 ml/kg, n = 4), inhibited the response to growth hormone releasing factor. In control studies with somatostatin infusion (50 micrograms/kg bolus followed by 50 micrograms/kg infusion for 2 h, n = 3), there was a significant (P less than 0.005) but partial decrease in growth hormone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888800 TI - Medical treatment of patients with Barrett's esophagus. PMID- 2888801 TI - A comparative study of metronidazole and sulfasalazine in active, not severe, ulcerative colitis. An Israeli multicenter trial. AB - Since metronidazole (M) was found to be effective in Crohn's disease, we evaluated its efficacy in the treatment of active ulcerative colitis (UC). Forty six outpatients with acute, nonsevere UC were studied. Forty-two concluded the trial. Twenty-three received M 1.35 g/day and 19 received sulfasalazine (S) 4.5 g/day for 28 days in a randomized double-blind study. Six of 23 receiving M improved (26%) as against 13 of 19 patients receiving S (68%) (p less than 0.01). No significant side effects were noted. We conclude that M is ineffective in the therapy of an acute attack of UC. PMID- 2888802 TI - Collagenous colitis and rheumatoid arthritis with response to sulfasalazine. A case report and review of the literature. AB - Collagenous colitis has been associated with rheumatoid arthritis in only a few cases. We describe a 76-year-old man with chronic rheumatoid arthritis whose diarrhea and abdominal pain came from collagenous colitis. He had a good clinical response to sulfasalazine. We review the clinical and histopathological features of collagenous colitis, together with the different therapeutic approaches. PMID- 2888803 TI - Sulfasalazine lung. Desensitization to sulfasalazine and treatment with acrylic coated 5-ASA and azodisalicylate. AB - A patient with ulcerative colitus developed fever, dyspnea, eosinophilia, and pulmonary infiltrates while taking sulfasalazine. The abnormalities resolved when the sulfasalazine was stopped but the colitus recurred. Desensitization to sulfasalazine was unsuccessful, but treatment with azodisalicylate (olsazine) controlled the colitus and did not cause pulmonary problems. PMID- 2888804 TI - Complement activation in patients with amebic liver abscess. AB - Serum or plasma concentrations of components of the classical (C1q, C4) and alternative (C3, factor B) pathways, regulatory protein factor H, and one of the C3 products of degradation, C3d, were determined in 19 patients with amebic liver abscess (ALA). Patients were divided into two groups. Thirteen patients that recovered under medical treatment who had a significantly shorter clinical course on admission (P less than 0.05) (group 1) exhibited either normal (C1q; C4; factor B; C3d) or increased levels of these components (C3, P less than 0.001; factor B, P less than 0.01). On the other hand, 16 patients that recovered after medical treatment and abscess drainage (group 2) exhibited significantly diminished serum levels of C1q (P less than 0.05), C3 (P less than 0.001), factor B (P less than 0.01) and factor H (P less than 0.05), and normal levels of C4, and C3d as compared to the control group. The relationships among the complement components studied were suggestive of activation of the complement system through the classical pathway in patients within group 1 and through both pathways in group 2. Sera of 3 out of the 5 patients who initially exhibited low plasma levels of C3d showed an increase during convalescence. Plasma levels of C3d were demonstrated to show a direct correlation with serum albumin and SGOT in this group of patients. Possible implications of the complement system in the immunopathogenesis of ALA are discussed. PMID- 2888805 TI - Vancomycin-resistant leuconostocs, lactobacilli and now pediococci. PMID- 2888806 TI - A hospital outbreak caused by a chlorhexidine and antibiotic-resistant Proteus mirabilis. AB - An outbreak of urinary-tract infection involving a strain of Proteus mirabilis resistant to gentamicin and several other antibiotics affected 90 patients in Southampton between July 1980 and May 1985. The outbreak strain was also resistant to chlorhexidine and this, in combination with the antibiogram and Dienes' test, permitted differentiation from other P. mirabilis strains. The outbreak had features in common with other Enterobacteriaceae outbreaks, although certain aspects of the population involved have made it particularly difficult to control. The outbreak commenced shortly after the introduction of a catheter care policy which involved the use of chlorhexidine, and although the majority of the cases were colonized before this policy was enforced, chlorhexidine had been used extensively for other procedures within the district. Preliminary evidence suggests that there is no genetic linkage between the chlorhexidine and multiple antibiotic resistance. PMID- 2888807 TI - Serotypes and biochemical profiles of British hospital strains of Enterobacter cloacae in relation to site of infection and antibiotic susceptibility. AB - Comparisons were made between the O-serotype, API 20E profile, site of isolation and antimicrobial resistance of clinical isolates of Enterobacter cloacae. Correlations were found between autoagglutinable strains and urinary-tract infection, and API 20E profile 3305573 and strains isolated from blood. The proportion of strains sensitive to amikacin, gentamicin, cefotaxime, cefuroxime and trimethoprim were 100%, 93%, 91%, 83% and 89%, respectively. No individual resistances or patterns of resistance were associated with O-serotype or biochemical profile. Strains isolated from urinary-tract infections were the most resistant, 40% being resistant to five or more antimicrobials compared to 18%, 12% and 4% for strains from blood, wounds and sputum, respectively. There were no readily identifiable phenotypes within E. cloacae that possessed unique characteristics that could contribute to infections in hospitals. PMID- 2888808 TI - The resistance of urinary tract pathogens to chlorhexidine bladder washouts. AB - Isolates of Providencia stuartii, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae and Streptococcus faecalis from urinary-tract infections in spinally-injured patients together with Escherichia coli 10418 were challenged with chlorhexidine (200 mg l-1) in a model of a catheterized bladder under conditions which simulate the bladder washout technique. All species survived the antiseptic. Organisms growing on the wall of the bladder model appeared to be particularly resistant and electron microscopy showed that these cells were embedded in a protective glycocalyx. The effect of chlorhexidine bladder washouts on the bacterial flora in the urine of patients was also observed and shown to be minimal and temporary. Examination of urinary sediments from patients revealed the presence of micro-colonies of bacteria embedded in a polysaccharide matrix. We conclude that bladder washouts with chlorhexidine are not likely to eliminate established infections with organisms that occur in patients with indwelling bladder catheters. PMID- 2888809 TI - Heat shocking as a useful adjunct to routine phage typing of Staphylococcus aureus. AB - The heat shock technique (heating a culture at 55 degrees C for 3 min immediately before phage typing) has been used in our laboratory as an adjunct to routine phage typing for 2 years. This has enabled phage typing patterns to be determined on isolates otherwise recorded as untypable. The method is easily performed and standardized. Phage patterns were found to be reproducible and adequate discrimination was achieved. We found the technique provided significant information which was not available by conventional typing. PMID- 2888810 TI - The effectiveness of ethanol gauze for hand disinfection in surgical wards. AB - The effectiveness of ethanol gauze in removing transient bacteria on the hands was investigated in a surgical ward during clinical nursing rounds. Two nurses with similar duties were selected as subjects for each round; one disinfected her hands with ethanol gauze when moving between patients while the other immersed her hands in 0.05% aqueous chlorhexidine gluconate when aware of contaminating her hands. Hand samples were taken after preliminary disinfection before the round, and again after the round on 37 occasions. Pseudomonas aeruginosa and Staphylococcus aureus were not detected in nurses using ethanol gauze, except in one nurse where S. aureus was isolated from both the pre- and postround hand culture. Both organisms were detected on four occasions from the postround hand cultures in the chlorhexidine group. Acinetobacter anitratus was not removed by pre-round disinfection, and was found on five and 11 occasions from the postround hand cultures in the ethanol gauze and chlorhexidine groups, respectively. PMID- 2888811 TI - Nosocomial legionellosis associated with use of oxygen bubble humidifiers and underwater chest drains. AB - In 1 year 12 of 48 patients who developed fatal pneumonia following admission with non-respiratory disorders to the Hospital Molinette, Torino, yielded Legionella pneumophila serogroup 1 from lung at autopsy. Patients were hospitalized on seven different wards for different conditions; only two of the wards had air conditioning but legionellas were not isolated from these. All patients were in poor health or immunocompromised. Some patients had inhaled humidified oxygen from piped supplies and three had undergone surgery. Legionella pneumophila serogroup 1 was detected in the water of oxygen bubble humidifiers and an underwater chest drain. The contaminated devices had been filled with tap or distilled water and the hospital water supply was found to be contaminated with L. pneumophila serogroup 1. Our findings suggest that filling bubble humidifiers or underwater chest drains with tap water is a potential hazard and should be avoided. PMID- 2888812 TI - The effects of cefotetan disodium on haemostasis. AB - A 7-day course of intravenous cefotetan disodium was given to nine patients. No significant changes were observed in haematological or biochemical parameters and serum vitamin K1 levels, prothrombin times, factor VII levels, thrombin times and activated partial thromboplastin times remained within the normal ranges throughout the treatment period in all patients. There was no evidence of clinical bleeding in any patient although in two the bleeding time was prolonged up to 13.0 min after 7 days' therapy. Notably, adenosine-5-diphosphate (ADP) induced platelet aggregation responses were significantly increased (P less than 0.05) at the end of the treatment period. These data indicate that cefotetan disodium at a dose of up to 4 g daily can be used without risk of a bleeding diathesis. In situations associated with vitamin K1 deficiency, potential prolongation of the prothrombin time should be avoided by prophylactic vitamin K1 administration. PMID- 2888814 TI - Salmonella screening of pregnant women. AB - Over a 9-year period all maternity patients were screened by rectal swab for salmonella excretion at the time of delivery. 30,471 mothers were screened and 60 (0.2%) yielded salmonellas, 43 (72%) of whom were symptomless excretors. Seven of the 60 babies (12%) excreted salmonellas, all of which were the same organism as in the mothers. Five had uncomplicated gastroenteritis in the neonatal period, but no mother or child suffered invasive disease and no incidents of hospital cross-infection occurred. These results show that screening is unjustified unless there are problems of cross-infection. PMID- 2888813 TI - The effect of antibiotic prophylaxis and topical antiseptics on the bacterial flora of the skin after cardiac surgery. AB - A controlled trial of antibiotic prophylaxis in cardiac surgery compared a two dose regimen of teicoplanin with a longer conventional course of flucloxacillin and tobramycin. In 12 patients the susceptibility of the bacterial skin flora of four different sites to each of the three antibiotics was determined and the results are reported here. Less than 1% of the Gram-positive colonies showed reduced sensitivity to teicoplanin (MIC greater than or equal to 4 mg l-1). Before operation, 99% inhibition of Gram-positive growth was achieved at 26 (54%) of 48 sites by 1 mg l-1 of flucloxacillin and 13 (27%) sites by 2 mg l-1 tobramycin. By the 7th day after operation there was a significant reduction in the number of sites showing similar sensitivity to flucloxacillin [16 (33%) sites, P less than 0.05]. The use of teicoplanin was not associated with the emergence of Gram-negative skin flora but tobramycin promoted acquisition of aminoglycoside-resistant strains. PMID- 2888815 TI - Outbreak of Shigella sonnei dysentery on a long stay psychogeriatric ward. AB - A ward outbreak of diarrhoea associated with Shigella sonnei on a long stay psychogeriatric ward is described. Nine patients and three staff had positive stool cultures for S. sonnei. The source of infection of the index case was not discovered. Environmental factors at ward level which predispose long stay hospitals to such outbreaks are discussed. PMID- 2888816 TI - Use of teicoplanin for Hickman catheter associated staphylococcal infection in immunosuppressed patients. AB - Antibiotic-resistant coagulase-negative staphylococci are a frequent cause of infection in indwelling central venous (Hickman) catheters. Teicoplanin has been evaluated in the treatment of 19 immunosuppressed patients with staphylococcal Hickman catheter infections, nine of whom were septicaemic. All infections were eradicated, with minimal side effects. In 16 cases, the catheter was retained until no longer required. Two recurrent infections were eradicated by a second course of teicoplanin. We conclude that teicoplanin is an effective and well tolerated antibiotic in the treatment of Hickman catheter infections in immunosuppressed patients. PMID- 2888817 TI - Chlorhexidine resistance among bacteria isolated from urine of catheterized patients. AB - Seventy-four of 155 catheter specimens of urine yielded organisms resistant to chlorhexidine. The inhibitory effect of urine against chlorhexidine is reported. PMID- 2888818 TI - Antibiotic dependence in a strain of Neisseria pharyngis. AB - A strain of Neisseria pharyngis was isolated in pure culture from a specimen of sputum. Growth was markedly enhanced by sub-lethal concentrations of rifampicin, spectinomycin, erythromycin and clindamycin. The effect was temporary with tetracycline. The possible mechanisms of this phenomenon are discussed. PMID- 2888819 TI - Silicone oil as a reservoir for nosocomial infection. AB - Two episodes of infection with epidemic methicillin-resistant Staphylococcus aureus (EMRSA) associated with silicone oil baths are described. In vitro studies indicated that certain organisms, including EMRSA, can survive in silicone oil for several days. We conclude that the oil acted as a reservoir for continuing infection in our patients. We suggest routine care of silicone oil baths in order to prevent cross infection. PMID- 2888820 TI - Sterility of incontinence pads and sheets. PMID- 2888821 TI - Relative stability of sodium hypochlorite liquids and sodium dichloroisocyanurate effervescent disinfectant tablets. PMID- 2888822 TI - The phenotype of thymocytes derived from a single clonogenic precursor. AB - Clonogenic repopulation of the thymus of thymus-homing bone marrow cells leads to intrathymic populations representing all four major Lyt-2- and L3T4-defined phenotypes. Although all four phenotypes may be represented in a single clone, quite often a striking bias in the proportion of L3T4 single positive to Lyt-2 single positive cells may exist within a clone, but not in the host thymocytes in general. Because at any one time these clones may be located in specific subregions of the thymus (specifically cortex only, medulla only, or cortex and medulla), we propose the hypothesis that different microenvironments in the thymus might, in fact, be responsible for the predominant maturation of different single positive mature thymic subsets. PMID- 2888823 TI - Inhibition of monocyte oxidative responses by Bordetella pertussis adenylate cyclase toxin. AB - Bordetella pertussis and the other Bordetella species produce a novel adenylate cyclase toxin which enters target cells to catalyze the production of supraphysiologic levels of intracellular cyclic adenosine monophosphate (cAMP). In these studies, dialyzed extracts from B. pertussis containing the adenylate cyclase toxin, a partially purified preparation of adenylate cyclase toxin, and extracts from transposon Tn5 mutants of B. pertussis lacking the adenylate cyclase toxin, were used to assess the effects of adenylate cyclase toxin on human peripheral blood monocyte activities. Luminol-enhanced chemiluminescence of monocytes stimulated with opsonized zymosan was inhibited greater than 96% by exposure to adenylate cyclase toxin-containing extract, but not by extracts from adenylate cyclase toxin-deficient mutants. The chemiluminescence responses to particulate (opsonized zymosan, Leishmania donovani, and Staphylococcus aureus) and soluble (phorbol myristate acetate) stimuli were inhibited equivalently. The superoxide anion generation elicited by opsonized zymosan was inhibited 92% whereas that produced by phorbol myristate acetate was inhibited only 32% by B. pertussis extract. Inhibition of oxidative activity was associated with a greater than 500-fold increase in monocyte cAMP levels, but treated monocytes remained viable as assessed by their ability to exclude trypan blue and continued to ingest particulate stimuli. The major role of the adenylate cyclase toxin in the inhibition of monocyte oxidative responses was demonstrated by: 1) little or no inhibition by extracts from B. pertussis mutants lacking adenylate cyclase toxin; 2) high level inhibition with extract from B. parapertussis, a related species lacking pertussis toxin; and 3) a reciprocal relationship between monocyte cAMP levels and inhibition of opsonized zymosan-induced chemiluminescence using both crude extract and partially purified adenylate cyclase toxin. Pertussis toxin, which has been shown to inhibit phagocyte responses to some stimuli by a cAMP independent mechanism, had only a small (less than 20%) inhibitory effect when added at concentrations up to 100-fold in excess of those present in B. pertussis extract. These data provide strong support for the hypothesis that B. pertussis adenylate cyclase toxin can increase cAMP levels in monocytes without compromising target cell viability or impairing ingestion of particles and that the resultant accumulated cAMP is responsible for the inhibition of oxidative responses to a variety of stimuli. PMID- 2888824 TI - The immune response to Schistosoma mansoni infections in inbred rats. VI. Regulation by T cell subpopulations. AB - These studies assess the roles of subpopulations of T lymphocytes in inducing and modulating resistance to Schistosoma mansoni. CDF rats were depleted of RT 7.1+ (anti-Pan-T), W3/25+ (anti-T helper/inducer), or OX8+ (anti-T suppressor) cells by the in vivo administration of monoclonal antibodies (mAb). The development of parasites and immunity to challenge by S. mansoni were compared with results in undepleted normal and congenitally athymic rats. Discrete subpopulations of T lymphocytes were adoptively transferred to ascertain effects upon parasite development and the protective immune response. In vitro studies, involving utilizing cocultivation of cell subpopulations +/- cyclosporin A, were utilized to dissect mechanisms. Depletion of T lymphocytes by anti-RT7.1 mAb and anti W3/25 mAb resulted in augmented initial worm development, suboptimal resistance, and decreased antibody and delayed-type hypersensitive reactivity directed against schistosome antigens. Depletion with OX8 mAb produced opposite effects. The adoptive transfer of T cell subpopulations produced concordant results with T cell regulation expressed B cell-dependent effector mechanisms. The coadoptive transfer of cells resulted in the suppression of resistance afforded by the W3/25+ cells by OX8+ cells, which could be augmented in vitro by cyclosporin A. Thus, protective immunity to S. mansoni in rats is regulated by discrete subpopulations of T lymphocytes. The findings suggest the possibility of selective immune regulation of resistance based on the manipulation of specific T cell subpopulation. PMID- 2888825 TI - Isolation of a 220-kilodalton protein with lectin properties from a virulent strain of Entamoeba histolytica. AB - A 220-kilodalton (kDa) protein with lectin properties was isolated from Entamoeba histolytica strain HM1:IMSS and was purified by Sepharose 4B chromatography and electroelution from 5% SDS-polyacrylamide gels. The protein contains 9% carbohydrate by weight; is rich in hydrophobic residues; and is very immunogenic in mice, hamsters, and rabbits. The protein binds to fixed monolayers of MDCK cells and inhibits trophozoite attachment to the cultured cells. The 220-kDa protein agglutinates human erythrocytes, and agglutination is inhibited by micromolar concentrations of hyaluronic acid, chitin, chitin-derived products (chitotriose), and antibodies to the purified protein. The 220-kDa protein is recognized by an antibody to the membrane but not by antibodies to other subcellular fractions. We therefore suggest that this 220-kDa protein with lectin properties is a component of the plasma membrane and could be one of the putative "receptor" molecules involved in cell and/or matrix attachment. PMID- 2888826 TI - Use of antibodies to characterize a 220-kilodalton surface protein from Entamoeba histolytica. AB - Antibodies were prepared against a 220-kilodalton (kDa) protein partially purified by Sepharose 4B chromatography of Entamoeba histolytica strain HM38:IMSS homogenates, and the protein was found to have lectin properties. The antibodies specifically recognized this protein in trophozoite homogenates. Immunologically related molecules with the same molecular weight were identified by polyclonal antibodies in strains HM1:IMSS, Entamoeba invadens, and Entamoeba histolytica Laredo. Six monoclonal antibodies recognized only the 220-kDa protein present in strains HM38 and HM1, a result indicating the presence of similar epitopes in the proteins from virulent strains isolated from humans. All the antibodies against the 220-kDa protein have the following properties: (1) they bind to the plasma membrane of live or fixed trophozoites, (2) they partially inhibit the adhesion of trophozoites to erythrocytes and cultured cells, and (3) they inhibit erythrophagocytosis. PMID- 2888827 TI - Colonization factor antigens and a new fimbrial type, CFA/V, on O115:H40 and H- strains of enterotoxigenic Escherichia coli in central Australia. PMID- 2888828 TI - [A case of Takayasu's arteritis associated with nephrotic syndrome, aortic regurgitation and amyloidosis]. PMID- 2888829 TI - Plasma growth hormone, somatostatin, insulin and glucagon inter-relationships during infusion of human pancreatic growth hormone-releasing factor in young and adult ducks (Anas platyrhynchos). AB - Human pancreatic GH-releasing factor (hpGRF) increased the concentrations of plasma GH when infused i.v. into immature ducks. A dose-dependent increase in plasma GH was observed within 10 min of the start of infusion and was maintained during the 30-min infusion period. Simultaneous infusion of somatostatin S-14 prevented the increase in plasma GH induced by hpGRF, but when the infusion had finished there was a rebound increase in plasma GH. Infusion of the highest dose of hpGRF (800 ng/kg per min) in adult ducks had no significant effect on plasma GH. Plasma somatostatin concentrations were reduced during the infusion of hpGRF in young but not in adult ducks. This observation suggests that the stimulatory effect of hpGRF on GH secretion may be partly due to its inhibitory effect on somatostatin secretion. Infusion of hpGRF in ducklings also increased the concentrations of glucagon and decreased levels of insulin in the plasma. Peripheral plasma glucagon and insulin levels in adult ducks were unaffected by hpGRF infusion. These results indicate that in ducklings, hpGRF increases plasma GH and glucagon concentrations and lowers plasma somatostatin and insulin levels. In the adult, these hormonal responses to hpGRF are not maintained. The highly stimulatory effect of hpGRF on GH secretion in ducklings may explain why plasma GH concentrations are high in these birds. PMID- 2888830 TI - The role of the hypothalamic beta-adrenergic system in controlling the LH rise in short-term castrated rats. AB - Intraventricular infusions of adrenaline and various pharmacological agents acting on beta-adrenergic receptor subtypes were carried out in rats orchidectomized 16 h previously. Infusions (10 microliter) of solutions containing the drugs were administered under anaesthesia induced with alphaxalone and alphadolone. Levels of LH were measured in plasma collected immediately before and at predetermined intervals after the infusion. The acute rise in LH levels after castration was increased still further by isoprenaline (a mixed beta 1- and beta 2-agonist), fenoterol (a beta 2-agonist) and atenolol (a beta 1 antagonist). In contrast, prenalterol (a beta 1-agonist) and (2RS,3RS)-3 isopropylamino-1-(7-methylindan-4-yloxy)++ +butan-2-ol (ICI 118,551) (a selective beta 2-antagonist) were inhibitory to LH release. Adrenaline itself, salbutamol (another selective beta 2-agonist), propranolol (a mixed beta-antagonist) and metoprolol (a beta 1-antagonist) did not significantly alter plasma LH concentrations at the doses administered. The stimulatory effect of isoprenaline on LH release was partially reduced when given together with ICI 118,551, but was not affected when administered simultaneously with atenolol. The inhibitory effect of ICI 118,551 was, however, prevented by concomitant administration with fenoterol, as was that of prenalterol when infused with atenolol. The results suggest that the hypothalamic mediation of the short-term changes in LH release in response to castration is exerted, at least in part, through the activation of a beta 2-stimulatory component and the suppression of a beta 1-inhibitory component. PMID- 2888831 TI - Undescended testis and hormone levels in early pregnancy. AB - A case-control study was carried out on mothers of boys with undescended testis to investigate the hypotheses that raised maternal levels of oestrogen or reduced levels of human chorionic gonadotrophin in early pregnancy might be factors in the environment of the fetus associated with this condition. No significant difference in the levels of either of these hormones was found, though, if anything, levels of oestrogen may have been lower in cases than in controls, and not higher as previously postulated. PMID- 2888833 TI - A determinant of resistance of Neisseria gonorrhoeae to killing by human phagocytes: an outer membrane lipoprotein of about 20 kDa with a high content of glutamic acid. AB - A protein of about 20 kDa was extracted by sodium cholate (1%, w/v) from outer membranes of a strain of Neisseria gonorrhoeae, BS4 (agar), which is resistant to killing by human phagocytes. When the protein was purified by repeated fractionation on Sephadex G75, contamination with other outer-membrane proteins and lipopolysaccharide was negligible. The protein contained a full complement of amino acids, with high levels of glutamic acid. Carbohydrate, detected by the anthrone method and by sugar and hexosamine analysis, was present, but at very low levels. There was a significant content of fatty acids (about 5.7% of the protein), indicating a lipoprotein. The 20 kDa lipoprotein: (1) neutralized the ability of antiserum against whole organisms of BS4 (agar) to reduce the resistance of this strain to phagocyte killing; (2) evoked in mice an antiserum which reduced this resistance and immunoblotted only with 20 kDa lipoprotein in the cholate extract of outer membranes; and (3) promoted resistance to intracellular killing of an otherwise phagocyte susceptible gonococcal strain (BSSH). This is strong evidence that it is a determinant of gonococcal resistance to phagocyte killing. PMID- 2888832 TI - Pathogenesis of arteritis of SL/Ni mice. Possible lytic effect of anti-gp70 antibodies on vascular smooth muscle cells. AB - The SL/Ni strain of mice spontaneously develops a necrotizing polyarteritis (NPA) that is histologically quite similar to human polyarteritis nodosa. This NPA most frequently affected parametrial tissues and/or ovaries of females and small arterioles of the major salivary glands. Electron microscopic studies of early arterial lesions revealed massive budding of C-type particles from arterial smooth muscle cells just before or at the onset of arteritis. In addition, binding of mouse IgG and C3 to the plasma membrane of virus-producing smooth muscle cells was shown by immunoelectron microscopy. Antibody-bound muscle cells showed disintegration of their plasma membrane, but degeneration and necrosis of muscle cells were not associated with dense infiltration of neutrophils. SL/Ni mice had natural antibodies that bound specifically to a fibroblast cell line infected with an endogenous ecotropic murine leukemia virus (MuLV) recovered from a SL/Ni mouse. Most of the natural antibodies were cytotoxic in the presence of murine complement. Western blot immunoassays revealed that among 14 SL/Ni female mice tested, all of the 9 mice that were affected by arteritis had anti-gp70 antibodies, while the 3 anti-gp70- mice were not affected. The presence of anti p30 or anti-p15 (anti-p12) antibodies, which were also detected in some SL/Ni mice, did not correlate with the development of arteritis. These results strongly support the hypothesis that NPA in SL/Ni mice is mediated by the lysis of arterial smooth muscle cells due to the deposition of cytotoxic natural antibodies directed to cell membrane-bound gp70 molecules of an endogenous ecotropic MuLV. PMID- 2888834 TI - Isolation of a repeated DNA sequence from Bordetella pertussis. AB - A repeated DNA sequence in the genome of Bordetella pertussis has been demonstrated. At least 20 copies of this sequence could be observed in either BamHI or EcoRI restriction enzyme digests of chromosomal DNA; fragments carrying the repeated DNA sequence ranged in size from about 1.5 to 20 kbp. The repeated DNA sequence was cloned from two separate regions of the B. pertussis genome, as shown by restriction enzyme site maps of the two clones and by hybridization studies. A small number of differences in the pattern of hybridization of the repeated DNA sequence to chromosomal DNA from several strains of B. pertussis was observed. No repeated DNA sequences were observed in one strain each of B. parapertussis and B. bronchiseptica, and there was no hybridization of B. pertussis DNA to Escherichia coli chromosomal DNA. The repeated DNA sequence was subcloned on a 2.54 kbp BamHI fragment from one of the two original clones. Restriction enzyme digests and hybridization studies showed that the repeated DNA sequence was about 1 kbp in size and had a single, internal ClaI site. PMID- 2888835 TI - Genetic analysis of variant pilin genes from Neisseria gonorrhoeae P9 cloned in Escherichia coli: physical and immunological properties of encoded pilins. AB - A series of genomic DNA fragments that encode gonococcal pilins from four well characterized pilus variants of Neisseria gonorrhoeae strain P9 have been cloned in Escherichia coli K12. At least nine classes of cloned P9 pilin genes have been identified on the basis of restriction mapping of cloned pilin-encoding DNA and physical and immunological analysis of expressed pilin proteins. Each antigenic variant of strain P9 possesses many genomic segments of pilin gene information, although our results suggest that strain P9 contains only a single pilin expressing (pilE) locus. PMID- 2888836 TI - Interaction of lactoferrin and transferrins with the outer membrane of Bordetella pertussis. AB - Bordetella pertussis was able to grow in vitro under conditions where the only iron present was bound to the iron-binding proteins ovotransferrin, transferrin or lactoferrin. Under these conditions the bacteria produced neither hydroxamate nor phenolate-catecholate siderophores to assist in the procurement of iron. Examination of B. pertussis outer-membrane preparations by SDS-PAGE and immunoblotting showed that the iron-binding protein ovotransferrin was bound directly to the bacterial surface. Assays of the binding of radiolabelled transferrin by the bacteria showed that the association was a specific process and that there was turnover of the bound proteins. Competitive binding assays indicated that lactoferrin could be bound in the same way. It is suggested that B. pertussis obtains iron directly from host iron-binding proteins during infection. PMID- 2888837 TI - Phage tf-1: a filamentous bacteriophage specific for bacteria harbouring the IncT plasmid pIN25. AB - Phage tf-1 is a filamentous phage which is about 800 nm in length, 10 nm in width and has slightly tapered ends. The phage was isolated from sewage and formed plaques or propagated only on Escherichia coli, Salmonella typhimurium and Klebsiella oxytoca strains harbouring the IncT plasmid pIN25 at 30 degrees C. It adsorbed in large numbers to pIN25-encoded long thick flexible conjugative pili formed at 30 degrees C and also to the short form of these pili synthesized at 37 degrees C. The reason for the failure to form plaques at 37 degrees C is not known. The adsorption site is a short length of the pilus shaft extending 100-200 nm back from the distal tip. Efficient phage tf-1 adsorption to the same site was found for pili determined by other IncT plasmids in spite of the fact that phage tf-1 did not plate or propagate on strains harbouring them. However, areas of specific partial clearing on lawns of these plasmid-containing bacteria were produced by phage in high concentrations. Lack of plaque-formation could be due to inefficient intracellular assembly coupled to avid adsorption of any liberated phage to pili. The phage differs from all but one other filamentous phage by being sensitive to diethyl ether. PMID- 2888838 TI - The involvement of glutamine synthetase/glutamate synthase in ammonia assimilation by Aspergillus nidulans. AB - Wild-type Aspergillus nidulans grew equally well on NH4Cl, KNO3 or glutamine as the only nitrogen source. NADP+-dependent glutamate dehydrogenase (EC 1.4.1.4) and glutamine synthetase (GS; EC 6.3.1.2) activities varied with the type and concentration of nitrogen source supplied. Glutamate synthase (GOGAT) activity (EC 1.4.7.1) was detected but it was almost unaffected by the type and concentration of nitrogen source supplied. Ion exchange chromatography showed that the GOGAT activity was due to a distinct enzyme. Azaserine, an inhibitor of the GOGAT reaction, reduced the glutamate pool by 60%, indicating that GOGAT is involved in ammonia assimilation by metabolizing the glutamine formed by GS. PMID- 2888839 TI - Impaired platelet aggregation and thromboxane generation in essential fatty acid deficient rats. AB - ADP-induced platelet aggregation and thrombin-induced thromboxane B2 generation in diluted whole blood from rats fed a fat-free diet supplemented with 10% (by weight) hydrogenated coconut oil [essential fatty acid (EFA) deficient] were significantly lower than that in animals fed 10% safflower oil [(SFO) rich in linoleic acid] or 10% marine oil (rich in eicosapentaenoic acid and docosahexaenoic acid). Plasma fibrinogen levels were significantly lower and liver function was impaired in the EFA-deficient group compared with the other two groups. Platelet responsiveness to ADP was restored when plasma from the EFA deficient rats was replaced by plasma obtained from rats fed a nonpurified diet. ADP responsiveness and thrombin-stimulated thromboxane B2 production in diluted whole blood were also restored after 2 wk of injections of 100 mg ethyl linoleate every 48 h, and partially restored by injections of 100 mg ethyl alpha linolenate. When ADP-induced platelet aggregation was examined in washed platelets, the impaired ADP aggregation (found when platelets of the EFA deficient rats were suspended in their own plasma) was not observed at either high (9.5 microM) or low (1.0 microM) ADP concentrations. Although thrombin stimulated thromboxane B2 production in washed platelets in the EFA-deficient rats was lower than that in the SFO-fed rats, the magnitude of aggregation was not different. In addition, inhibition of thrombin-induced platelet aggregation by apyrase (0.06 U/mL) was identical in the two groups. These results suggest that impaired platelet aggregation in EFA deficiency is related more to plasma factors than to inherent platelet properties and that restoration of normal liver function is associated with normal platelet function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888840 TI - Effect of locally generated angiotensin II on noradrenergic neuroeffector function in the rat isolated caudal artery. AB - The effects of angiotensin II and its precursors angiotensin I and tetradecapeptide renin substrate were investigated in isolated segments of the rat caudal artery. Each peptide constricted the rat caudal artery and also enhanced vasoconstrictor responses to sympathetic nerve stimulation (0.5 Hz, 10 s). The threshold concentrations for each peptide in enhancing sympathetic vasoconstrictor responses were lower than those required to produce vasoconstriction. Tetradecapeptide renin substrate was the least potent of the three peptides and had the slowest onset of action. Angiotensin II and angiotensin I each enhanced noradrenergic transmission to the same degree, whether perfused through the lumen or added to the adventitial surface of the artery. In contrast, tetradecapeptide renin substrate was more potent when applied to the adventitial surface. The effects of angiotensin I were blocked by the converting enzyme inhibitor enalaprilat, whereas the effects of tetradecapeptide renin substrate were unaltered by enalaprilat, or by the renin inhibitors pepstatin or a decapeptide renin inhibitor. These findings suggest that tetradecapeptide renin substrate and angiotensin I may be converted to angiotensin II within the rat caudal artery, with subsequent enhancement of noradrenergic neuroeffector function. However, the enzyme responsible for the conversion of tetradecapeptide renin substrate cannot be determined from the present findings. PMID- 2888841 TI - Three additional DNA polymorphisms in the met gene and D7S8 locus: use in prenatal diagnosis of cystic fibrosis. AB - We have used cloned DNA sequences from the 5' end of the met locus and the D7S8 locus to locate new restriction fragment length polymorphisms. TaqI and MspI polymorphisms with frequencies of 0.34/0.66 and 0.10/0.90, respectively, for met and a PvuII polymorphism (0.15/0.85) at D7S8 are described. We used these new markers to analyze our reference panel of cystic fibrosis pedigrees and found that they provided additional information in several families. No evidence for recombination was observed between the 5' end of met and previously described met markers. We present examples of the use of the met markers in the clinical diagnosis of cystic fibrosis and summarize our analysis of 29 clinical cases including eight prenatal diagnoses. We conclude that DNA-based prediction of cystic fibrosis is an effective clinical diagnostic procedure. PMID- 2888842 TI - Long-term treatment of refractory neonatal hypoglycemia with long-acting somatostatin analog. PMID- 2888843 TI - Prenatal diagnosis of cystic fibrosis. PMID- 2888844 TI - Gastrointestinal manifestations of Sipple syndrome in children. AB - The diagnosis and management of patients with multiple endocrine neoplasia (MEN) type IIA and type IIB are of special challenge to pediatric surgeons. Patients characteristically present early in life with significant intestinal symptoms at a time when the characteristic phenotypic features of MEN IIB are frequently absent. We are reporting 12 patients with MEN type II (9 with type IIA and 3 type IIB or Sipple's syndrome), all of whom presented with gastrointestinal manifestations. All 12 patients had signs and symptoms of bowel obstruction during the neonatal period. An unusual association of Hirschsprung's disease and MEN IIA was noted in our nine patients found among a kindred of 92 individuals. All three patients with Sipple's syndrome (MEN IIB) had severe gastrointestinal symptoms since birth, including recurrent pseudoobstruction. The possibility of MEN type II should be considered in all cases of bowel obstruction in the newborn period. Screening for medullary carcinoma of the thyroid must be carried out from infancy. A detailed family history is very important to avoid unnecessary surgery for bowel obstruction in Sipple's syndrome. PMID- 2888845 TI - A comparative investigation of glycinebetaine and dimethylsulphoxide as liposome cryoprotectants. AB - The release of streptomycin from lecithin liposomes following a freeze-thaw cycle was used to measure the cryoprotective activities of glycinebetaine and dimethylsulphoxide (DMSO). At concentrations between 4 and 8% w/v in the external solution, glycinebetaine was superior to DMSO at freezing rates faster than 50 degrees C min-1. At lower rates their activities were similar, and drug loss ranged between 10 and 20% depending upon freezing rate and cryoprotectant concentration. The pattern of streptomycin loss when the concentrations of cryoprotectants inside and outside the liposome were varied indicated that glycinebetaine, in contrast to DMSO, does not diffuse across the liposome membrane. The activity of glycinebetaine was not impaired by the presence in the membrane of cholesterol or charged lipids. PMID- 2888846 TI - The influence of viscosity on the migration of chloramphenicol and 4 hydroxybenzoic acid through glycerogelatin gels. AB - Migration of chloramphenicol and 4-hydroxybenzoic acid from solutions in 1 octanol into Glycerol Suppository Base, BP and soft gelatin capsule shells is reported. Rates of migration through the gels, quantified in terms of diffusion coefficients, are given. An electron spin resonance probing technique was used to determine the microscopic viscosity. The latter, rather than the bulk viscosity, was shown to be the major rheological influence on the rate of diffusion. PMID- 2888847 TI - Common ion effect on solubility and dissolution rate of the sodium salt of an organic acid. AB - The solubility and the dissolution rate of the sodium salt of an acidic drug (REV 3164; 7-chloro-5-propyl-1H,4H-[1,2,4]triazolo[4,3-alpha]quinoxaline-1,4-dione) decreased by the effect of common ion present in aqueous media. The solubility of the sodium salt of REV 3164 in a buffered medium was much lower than that in an unbuffered medium. Also, the presence of NaCl decreased its solubility in water. The apparent solubility product (K'sp) of the salt, however, did not remain constant when the concentration of NaCl was changed. A decrease in K'sp value with the increase in NaCl concentration was observed; for example, the K'sp values at 0 and 1 M NaCl were 7.84 X 10(-4) and 3.94 X 10(-4) M2, respectively. Even when corrected for the effect of ionic strength, the solubility product decreased. This decrease in the solubility product in the presence of NaCl indicated a decrease in the degree of self-association (increase in activity coefficient) of the drug in aqueous media. PMID- 2888848 TI - Effect of moderate haemodilution with Fluosol-DA or normal saline on indocyanine green and (+)-propranolol kinetics. AB - Indocyanine green (ICG) and (+)-propranolol kinetics were determined in the rat following moderate (50%) blood exchange with either Fluosol-DA or 0.9% NaCl (saline). Rats received an intravenous ICG dose (5 mg kg-1) before an intravenous dose of (+)-propranolol (2.5 mg kg-1) 0.5, 24, 48 or 72 h after haemodilution and were compared with non-exchanged controls. Haemodilution with Fluosol-DA reduced the ICG elimination rate constant during the first 24 h while a significant reduction was seen 48 h after normal saline exchange. ICG clearances tended to be less than the control value, and were significantly reduced only at 24 h after Fluosol-DA exchange due to a reduced Varea. (+)-Propranolol half-life was significantly increased 48 and 72 h after saline exchange; (+)-propranolol clearance was also significantly reduced 72 h after Fluosol-DA exchange. ICG clearance may be reflecting a hypovolaemic change which occurs after haemodilution, which would reduce the hepatic blood flow. However, (+) propranolol clearance was not altered, suggesting that the hepatic blood flow is not changed. It is possible that ICG clearance is changed due to alterations in its extraction ratio instead of hepatic blood flow changes. PMID- 2888849 TI - Cyclosporin: measurement of fraction unbound in plasma. AB - A reproducible ultracentrifugation method has been developed for the measurement of the fraction of cyclosporin (CyA) unbound in plasma. The sample is centrifuged to remove any particulate matter, ultracentrifuged in polyallomer tubes and then frozen in liquid nitrogen. Appropriate sections are then cut from the tube for determination of the concentration of radioactivity and calculation of fraction drug unbound. Using this method, the fraction unbound has been measured in plasma from renal transplant patients receiving CyA and found to range between 0.04 to 0.122. The binding is temperature-dependent and principally hydrophobic. PMID- 2888850 TI - Effect of nadolol, a beta-adrenoceptor blocking agent, on myocardial metabolism in the dog ischaemic heart. AB - The effect of nadolol at a dose of 1 mg kg-1, i.v. on the ischaemic myocardial metabolism has been examined in the dog. Ischaemia was induced by ligating the left anterior descending coronary artery for 3 min, and nadolol was injected 5 min before ligation. Ischaemia caused myocardial metabolic changes; it decreased energy charge potential and inhibited glycolytic flux through phosphofructokinase reaction. Pretreatment with nadolol lessened the decrease in energy charge potential and the inhibition of glycolytic flux being caused by ischaemia. Nadolol may have a beneficial effect on the ischaemic myocardium. PMID- 2888851 TI - Influence of pinacolyl dimethylphosphinate on soman storage in rats. AB - Atropinized rats pretreated with pinacolyl dimethylphosphinate (PDP) or saline were intoxicated with 6 X LD50 soman and, after 30 and 60 min, the absolute amounts of soman in diaphragms and lungs were measured gas chromatographically. The absolute amounts of free soman in both types of tissues were similar and were decreased after 60 min intoxication compared with the 30 min intoxication period. Pretreatment of rats with PDP reduced the amount of soman in the tissues by 63 78%. Incubation of isolated diaphragms and lungs with sodium fluoride (2.5 mM) increased the amount of free soman in these tissues by 2.6 X 10(3) and 16 X 10(3)%, respectively. An assay to study the binding of tritiated PDP was developed. Although this assay was suitable to study the binding of tritiated quinuclidinyl benzilate to rat brain, no binding between tritiated PDP and diaphragm or brain tissue could be detected. It was concluded that PDP may counteract soman storage by another mechanism than occupation of binding sites. PMID- 2888852 TI - Alcuronium pharmacodynamics in dogs: effect-concentration relationships in the diaphragmatic and limb muscles. AB - Previous studies suggest that the muscles of the diaphragm are less sensitive to neuromuscular blocking agents than the limb muscles. However, this difference has not been characterized directly in terms of relaxant drug plasma concentrations. The pharmacodynamics of the non-depolarizing muscle relaxant alcuronium were therefore investigated in nine dogs using a constant-rate infusion regimen with simultaneous measurement of muscle paralysis in the limb and diaphragm. Maximum paralysis between 95 and 100% was achieved in both muscle groups, within approximately the same time interval. However, during onset of and offset of effect, the pharmacodynamic parameters ECp50 and ECp95 for the limb muscle were lower than in the diaphragm. From a pharmacodynamic effect model it was also predicted that Css(50) and Css(95) for the limb muscles are half those values for the diaphragm. Thus, the diaphragm is less sensitive to the action of alcuronium than are limb muscles. The half-time for equilibration of alcuronium between plasma and the effect site was two-fold lower for the diaphragm, and the rate of recovery from paralysis in diaphragmatic muscles was twice that observed in limb muscles. Collectively, these data suggest that there is a greater margin of safety in the diaphragmatic muscles and that the response of the peripheral limb muscles to nerve stimulation provides only a conservative index of recovery from competitive neuromuscular block in the diaphragmatic muscles. PMID- 2888853 TI - Effects of diclofenac sodium and disodium ethylenediaminetetraacetate on electrical parameters of the mucosal membrane and their relation to the permeability enhancing effects in the rat jejunum. AB - The effects of diclofenac sodium and disodium ethylenediaminetetraacetate (EDTA) on electrical parameters of rat jejunal membrane were investigated, together with measurement of the mucosal-to-serosal flux of sulphanilic acid or L phenylalanine. Both adjuvants increased the flux rate of sulphanilic acid to a similar extent when added to the mucosal solution at 10 mM, but there were apparent differences in their effects on the electrical parameters. The addition of EDTA induced the gradual reduction in the membrane resistance (Rm) by 6-8 ohm cm-2, while the effect of diclofenac on Rm was complicated and concentration dependent. The short circuit current (Isc) was reduced rapidly to the level of 30 40 microA cm-2 by the addition of diclofenac, but was less affected by EDTA. The flux rate of L-phenylalanine was decreased extensively by diclofenac or the 10 mM concentration of EDTA, suggesting an inhibition of carrier-mediated transport systems in the membrane. Together with our preceding communication (Yamashita et al 1985, J. Pharm. Pharmacol. 37: 512-513), it became obvious that the sites of action of diclofenac and EDTA were different, the former directly interacting with the epithelial cell to alter the permeability and functions of the cell membrane, while the primary effect of EDTA could be at the intercellular junctions. PMID- 2888854 TI - L-dopa esters as potential prodrugs: behavioural activity in experimental models of Parkinson's disease. AB - Intraperitoneal administration of the 2-tetrahydropyranylmethyl, phenoxyethyl, ethyl, 2-hydroxypropyl and methyl ester prodrugs of L-dopa produced locomotor activity in reserpine-pretreated mice with equal intensity and duration to that observed following administration of L-dopa itself. Administration of the 2-(1 methoxy)propyl ester produced a more prolonged effect while the p methoxyphenylethyl, n-propyl, phenylethyl, m-trifluoromethylbenzyl, cyclohexyl, p chlorophenylethyl and benzyl ester prodrugs were less active than L-dopa itself. On oral administration, the ethyl and methyl ester prodrugs were more effective than L-dopa in reversing reserpine-induced akinesia in mice. The 2 tetrahydropyranylmethyl, 2-(1-methoxy)propyl, 2-hydroxypropyl, n-propyl, benzyl and phenoxyethyl ester prodrugs produced effects comparable with those of L-dopa. In contrast, the cyclohexyl, m-trifluoromethylbenzyl, phenylethyl, p chlorophenylethyl and p-methoxyphenylethyl ester prodrugs were less effective than L-dopa on oral administration. Intraperitoneal administration of L-dopa and the ester prodrugs of L-dopa to rats with a prior 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle (MFB) produced contraversive circling responses. Rotation observed following administration of the n-propyl, 2 tetrahydropyranylmethyl, methyl and ethyl ester prodrugs was more intense than that observed following administration of L-dopa itself. Rotation produced by the administration of L-dopa and the cyclohexyl, 2-(1-methoxy)propyl, phenylethyl, p chlorophenylethyl, p-methoxyphenylethyl, benzyl, 2-hydroxypropyl, phenoxyethyl and m-trifluoromethylbenzyl ester prodrugs was identical. Ester prodrugs of L dopa may be as effective as L-dopa itself in producing motor activity but overall none of the compounds tested was markedly more potent or of longer duration than L-dopa itself. PMID- 2888855 TI - The cardiovascular actions of dopexamine hydrochloride, an agonist at dopamine receptors and beta 2-adrenoceptors in the dog. AB - The receptor pharmacology of the cardiovascular effects of dopexamine hydrochloride in the anaesthetized dog (given by i.v. infusion of 3 X 10(-9)-10( 7) mol kg-1 min-1) has been analysed by the use of selective receptor antagonists and of ganglionic blockade. The increases in cardiac output, contractility, and rate were antagonized by the beta 2-adrenoceptor antagonist, ICI 118551. Renal blood flow rose secondary to reduction in renal vascular resistance and this was antagonized by SCH 23390, a highly selective DA1-receptor antagonist. Peripheral vasodilation and reduction of blood pressure were mediated by a combination of DA1- and DA2-receptor and beta 2-adrenoceptor stimulation. In a separate group of dogs, the cardiac stimulant effects of dopexamine HCl were partially reflex and were reduced by ganglion block, revealing responses due to stimulation of cardiac beta 2-adrenoceptors. Thus the beta 2-adrenoceptor agonist action of dopexamine HCl is not only partly responsible for afterload reduction but also leads to direct cardiac stimulation. From its cardiovascular profile, dopexamine HCl is likely to be of use in acute treatment of heart failure. PMID- 2888856 TI - Water distribution in creams prepared using cetostearyl alcohol and cetrimide. AB - The water distribution in an antiseptic cream formulation prepared using cetostearyl alcohol and cetrimide has been studied using thermogravimetric analysis, differential scanning calorimetry, ultracentrifugation and scanning electron microscopy. In addition to a free water phase two types of interlamellarly fixed water were found, one associated with the liquid crystalline network around the oil droplets and one associated with the liquid crystalline network of the bulk. The latter was in equilibrium with the free water and can be classed as freely drainable. PMID- 2888857 TI - Fundamental properties of metronidazole formulations in relation to tableting. AB - A study has been made of the effects of polyvinylpyrrolidone, gelatin and methylcellulose binding agents on the fundamental and tableting properties of a metronidazole-lactose-starch formulation. A material constant, alpha, was derived from the measured values of tensile strength of the materials. The values of alpha for the formulations are lower than that for metronidazole and depend on the nature and concentration of binder present. In terms of tableting properties, alpha supplements the information obtained from the ratios of elastic recovery to plastic compression (ER/PC) and from the brittle fracture index values (BFI) of the materials, although its influence appears to be limited at low values of ER/PC. PMID- 2888858 TI - Determination of the apparent failure viscosity of tablets. AB - Quantitative differences in the plasticity of several direct compression excipients were found to be distinguishable using normalized work of failure determinations. New parameters were developed to characterize the importance of changes in strain rate application during a diametral crushing test. Failure viscosity was found to have a similar sensitivity to normalized work of failure measurements and was also able to distinguish small changes in plastic behaviour. In cases where it is not possible to measure tablet deformation during tablet crushing, failure viscosity determinations could provide an alternative method for characterizing differences in deformation behaviour. PMID- 2888859 TI - Unloaded polyisobutylcyanoacrylate nanoparticles: efficiency against bloodstream trypanosomes. AB - The potential use of polyisobutylcyanoacrylate nanoparticles in antiparasitic chemotherapy is described. The nanoparticles on their own proved to have trypanocidal activity against Trypanosoma brucei brucei in-vitro but not against Trichomonas vaginalis or Entamoeba histolytica. The trypanocidal activity was partly confirmed in-vivo with T. brucei-infected mice. PMID- 2888860 TI - The biliary excretion of acenocoumarol in the rat: stereochemical aspects. AB - Within 24 h, 50% of a single dose of the acenocoumarol enantiomers was recovered in bile and 20% in urine of Wistar rats. The elimination products were mainly (greater than 90%) the 6- and 7-hydroxyacenocoumarol as conjugates in the bile but free in the urine. Only R-acenocoumarol, free and conjugated, was excreted in bile. There were no gross differences between the enantiomers in metabolic pattern or in the amount of metabolites formed. A significant difference was observed for the biliary excretion of the 7-hydroxy metabolite; the ratio of free and conjugated 7-hydroxyacenocoumarol was three times higher for the S- than for the R-isomer. An unknown third metabolite was recovered in bile in higher amounts with the S- than with the R-acenocoumarol. Only traces of this metabolite were recovered from urine. The data show an extensive biliary excretion of acenocoumarol and demonstrate stereoselective mechanisms in the excretion processes. PMID- 2888861 TI - Non-specific prolongation of the effects of general depressants by pyrazole and 4 methylpyrazole. AB - The liver alcohol dehydrogenase inhibitors, pyrazole and 4-methylpyrazole, have been tested for their ability to prolong drug-induced sleep times in mice. Both drugs (at 1 mmol kg-1 i.p.) prolonged the duration of loss of righting reflex following chloral hydrate, pentobarbitone, barbitone, temazepam and halothane, but not diethyl ether. This suggests that the effects of these pyrazoles are not specific to the inhibition of liver alcohol dehydrogenase. PMID- 2888862 TI - Inhibitory role of D-1 dopamine receptors for the jerks induced by B-HT 920 in rats. AB - Jerks of the head and upper trunk produced by the dopamine agonist B-HT 920 in reserpine-treated rats were abolished by the D-1 dopamine receptor agonist SKF 38393. The combined treatment with SKF 38393 and B-HT 920 instead resulted in stereotypies and locomotion. B-HT 920 also caused jerks when given after the D-1 receptor antagonist SCH 23390 to rats not pretreated with reserpine. The results indicate that B-HT 920 induces jerks by stimulation of postsynaptic D-2-like dopamine receptors provided that the D-1 receptors are not activated. PMID- 2888863 TI - The effects of acute reserpine administration on the sensitivity of the isolated pacemaker from rat heart to isoprenaline and noradrenaline. AB - The effects of reserpine on the sensitivity of the isolated pacemaker from rat heart to the chronotropic effect of isoprenaline and noradrenaline were studied. A single large dose of reserpine (2.5 mg kg-1) administered to rats 24 h before killing induces supersensitivity of the isolated pacemaker to isoprenaline, leaving unaltered the responsiveness of the pacemaker to noradrenaline. Reserpine at the dose of 1.0 mg kg-1 did not alter the sensitivity of the pacemaker to the catecholamines. Only the larger dose of reserpine raised the corticosterone plasma level. It is possible that a corticosterone-mediated inhibition of the extraneuronal uptake process is responsible for the supersensitivity to isoprenaline. Large doses of reserpine should not be used in experiments aimed to study cardiac sensitivity to isoprenaline or extraneuronal uptake and metabolism of the catecholamine. PMID- 2888864 TI - Stereoselective blockade of central [3H]5-hydroxytryptamine binding to multiple sites (5-HT1A, 5-HT1B and 5-HT1C) by mianserin and propranolol. AB - The interaction of the enantiomers of mianserin and propranolol with the binding of [3H]5-hydroxytryptamine ([3H]5-HT) to the 5-HT1A, 5-HT1B and 5-HT1C sites, and with the binding of [3H]ketanserin to the 5-HT2 site, has been evaluated in rat brain membranes. A stereoselective interaction at the 5-HT1A, 5-HT1B and 5-HT1C sites was demonstrated for both compounds, with (+)-mianserin being a more potent displacer than (-)-mianserin and (-)-propranolol being more potent than (+) propranolol. Only mianserin interacted in a stereoselective manner with the 5-HT2 site, (+)-mianserin being the more potent isomer. The stereoselective association of mianserin and propranolol with the 5-HT1A, 5-HT1B and 5-HT1C sites may prove useful in the characterization of these sites. PMID- 2888865 TI - Persistent depletion of striatal dopamine and its metabolites in mice by TMMP, an analogue of MPTP. AB - TMMP (1-methyl-4-[methylpyrrol-2-yl]-1,2,3,6-tetrahydropyridine) mimicked MPTP (1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in causing persistent depletion of striatal dopamine and its metabolites one week after the last of four daily subcutaneous injections in mice. MMPP (1-methyl-4-[1-methylpyrrol-2-yl]-4 piperidinol) produced no depletion of dopamine or its metabolites under these conditions. None of the three compounds affected dopamine or its metabolites when administered orally. TMMP was even more rapidly oxidized by type B monoamine oxidase in-vitro than was MPTP, but MMPP was a very poor substrate for the enzyme. The lack of neurotoxicity of MMPP toward nigrostriatal dopamine neurons when it was given orally or subcutaneously to mice contrasts with previously reported results in monkeys, in which case MMPP was reported to be neurotoxic. PMID- 2888866 TI - Gastric ulcerogenicity of non-steroidal anti-inflammatory drugs in mice with mucosa sensitized by cholinomimetic treatment. AB - A novel technique is described for the assay of acute gastric irritancy of non steroidal anti-inflammatory drugs (NSAIDs) in mice in which (a) the gastric mucosa is sensitized to the irritant actions of the drugs by co-administration of bethanechol chloride to increase acid and pepsin production, and (b) the area and number of haemorrhagic lesions in the glandular mucosa is measured quantitatively by visual image analysis. The technique has been used to assess the acute gastric irritancy of 20 NSAIDs in mice. In relation to published values for their acute and chronic anti-inflammatory activities, drugs with low relative gastric irritancy (e.g. carprofen, chloroquine, diclofenac, fenbufen, tenoxicam, tilomisole) were differentiated from the drugs of higher relative irritancy. PMID- 2888867 TI - Photolytic degradation of benorylate: effects of the photoproducts on cultured hepatocytes. AB - The photodegradation of benorylate [4'-(acetamido)phenyl-2-acetoxybenzoate], a drug frequently used in rheumatoid arthritis therapy, has been examined under different sets of experimental conditions. Several photoproducts have been isolated and identified on the basis of their IR, NMR, and MS spectra. The most significant photochemical process is the photo-Fries rearrangement of benorylate, leading to 5-acetamido-2'-acetoxy-2-hydroxybenzophenone (1). This compound undergoes a rapid transacylation to the isomeric 5'-acetamido-2'-acetoxy-2 hydroxybenzophenone (2). A primary culture of rat hepatocytes has been used to evaluate the possible toxicity of these two benzophenones, keeping in mind the following criteria: leakage of cytosolic enzymes, attachment index to culture plates, gluconeogenesis from lactate and fructose, glycogen balance, and albumin synthesis. At the concentrations assayed, neither of the two major photoproducts of benorylate (benzophenones 1 and 2) had significant toxic effects on liver cells in culture. PMID- 2888868 TI - Selective ganglionic blockade of vagal inputs to sinoatrial and/or atrioventricular regions. AB - Vagal postganglionic neurons to sinoatrial (SAN) and atrioventricular (AVN) nodal regions of the canine heart have been localized surgically around the right pulmonary vein-atrial fat pad and in the fat pad overlying the epicardium at the inferior vena cava-inferior left atrial junction, respectively. Local ganglionic blocking doses (total of 5 mg per injection) of hexamethonium were injected into the pulmonary vein-atrial fat pad to block selectively right and left vagal inputs to the SAN region without interrupting vagal inputs to AVN. Conversely, hexamethonium injected into the inferior vena cava-inferior left atrial pad selectively blocked vagal control of arteriovenous conduction without interfering seriously with vagal control of SAN function. Vagal ganglia situated in pulmonary vein-atrial fat pad also exercise moderate but incomplete control of right atrial contractile force. Lesser vagal control of atrial inotropism is localized in the inferior vena cava-inferior left atrial fat pad. Ganglia situated in a large fat pad on the dorsal epicardial surface of the left atrium (left atrial fat pad) appear to play little or no role in SAN or AVN regulation, although some left preganglionic axons may pass through it en route to the AVN region. Vagal stimulation is associated with prompt and profoundly negative chronotropic and dromotropic responses, but in response to the same stimulation, a negative change in atrial contractile force is much slower in development and is much longer lasting. Such precise anatomical localization and differentiation of the intrinsic vagal regulation of SAN, AVN and contractile force opens new avenues of research on the neural regulation of cardiac performance. PMID- 2888869 TI - Comparative analysis of beta-1 adrenoceptor agonist and antagonist potency and selectivity of cicloprolol, xamoterol and pindolol. AB - The partial beta adrenoceptor agonist properties of cicloprolol, xamoterol and pindolol have been compared in vivo (anesthetized catecholamine-depleted or pithed rats) and in vitro (guinea pig or rat right atria and guinea pig tracheal muscle preparations) conditions. All three compounds increased heart rate in the former preparations, and their intrinsic activities relative to isoproterenol were 0.7, 0.65 and 0.45, respectively. The positive chronotropic effects of cicloprolol or xamoterol were competitively antagonized by betaxolol or propranolol; however, part of those induced by pindolol were resistant to these beta adrenoceptor antagonists. None of these compounds increased the spontaneous beating rate of isolated guinea pig atria; however, xamoterol only increased heart rate in isolated rat atria, and its intrinsic activity with respect to isoproterenol was 0.4. Pindolol, xamoterol and cicloprolol behaved as competitive beta-1 adrenoceptor antagonists against isoproterenol-induced tachycardia in a pithed rat model. In order to mimic the intrinsic effects of the partial agonist drugs, control dose-response curves for isoproterenol were determined in pithed rats in which the base-line heart rate was elevated by thoracic spinal cord stimulation. In this in vivo preparation, xamoterol and pindolol were more potent beta-1 adrenoceptor antagonists than cicloprolol; however, cicloprolol and xamoterol, in contrast to pindolol, were selective for beta-1 adrenoceptors. In isolated spontaneously beating guinea pig right atria, cicloprolol and xamoterol were equipotent beta-1 adrenoceptor antagonists but were about 50 times less potent than pindolol. In isolated rat atria, the beta-1 adrenoceptor antagonist potency of xamoterol was greater (pA2 = 8.7) than in guinea pig atria (pA2 = 7.8). The potencies of cicloprolol and pindolol did not vary between these species. In catecholamine-depleted rats, high i.v. doses of cicloprolol had vasodilator activity that was partly mediated by beta-2 adrenoceptors. In carbachol-contracted guinea pig trachea, cicloprolol and xamoterol, in contrast to pindolol, were relatively inactive against isoproterenol-induced relaxation. In conclusion, cicloprolol and xamoterol, similarly to pindolol, behave as agonists and antagonists of beta-1 adrenoceptors. However, only cicloprolol and xamoterol show an elevated degree of selectivity toward the beta-1 adrenoceptor subtype. PMID- 2888870 TI - Pharmacological analysis of the cardiac actions of xamoterol, a beta adrenoceptor antagonist with partial agonistic activity, in guinea pig heart: evidence for involvement of adenylate cyclase system in its cardiac stimulant actions. AB - The pharmacological effects of xamoterol, a beta adrenoceptor antagonist with partial agonistic activity, were examined in guinea pig cardiac preparations and compared with those of isoproterenol to assess possible mechanisms of its cardiac stimulant actions. Xamoterol produced a positive inotropic effect in the papillary muscles and a positive chronotropic effect in the spontaneously beating right atria in a concentration-dependent manner. The maximum inotropic and chronotropic effects of xamoterol were about 33 and 35% of those of isoproterenol, respectively. Although xamoterol failed to produce a consistent increase in contractile force in the left atria, the positive inotropic effect of the agent was observed clearly in preparations obtained from reserpine-pretreated animals. The positive inotropic and chronotropic effects of xamoterol were antagonized by atenolol, but not by ICI 118,551. On the other hand, xamoterol antagonized competitively the positive inotropic and chronotropic responses to isoproterenol. In papillary muscles the increases in contractile force induced by xamoterol and isoproterenol were depressed markedly in the presence of carbachol or adenosine. In all of left atria, right atria and papillary muscles obtained from reserpine-pretreated animals, xamoterol caused a significant elevation in cyclic AMP levels, while inhibiting the isoproterenol-induced increase in cyclic AMP levels. Computer-assisted analysis of concentration-response curves for the inhibition by xamoterol of the binding of [125I]iodocyanopindolol in the membranes from guinea pig ventricles showed the existence of the 5' guanylylimidodiphosphate sensitive, highly affinity site of beta adrenoceptors for xamoterol, suggesting that xamoterol may induce the formation of a ternary complex with the beta adrenoceptor and a stimulatory guanine nucleotide regulatory protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888871 TI - Palytoxin-induced contraction and release of prostaglandins and norepinephrine in the aorta. AB - Mechanism of action of a potent marine toxin, palytoxin (PTX), in blood vessels was examined using rat and rabbit aortas. PTX in the concentrations of 10(-10) to 10(-8) M induced contraction in rat aortas. The rate of rise of contraction and the maximum contractile tension due to 10(-10) M PTX became greater when endothelium was removed from aortic strip. Methylene blue, 5 X 10(-6) M, also increased both the rate of rise and maximum tension. These results suggest that PTX may release a relaxing substance from endothelium which may inhibit the contraction induced by PTX itself. In contrast to this, the 10(-8) M PTX-induced contraction became smaller when endothelium was removed from the aorta. This contraction was partially inhibited by 10(-5) M indomethacin. Verapamil (10(-6) M) also inhibited a portion of this contraction and these inhibitors showed an additive inhibitory effect. Prazosin (10(-7) M) did not affect this contraction. Similar results were obtained in aortas without endothelium. Using thin-layer chromatography, it was found that PTX (10(-8) M) increased the release of prostaglandin E2, F2 alpha and 6-keto-prostaglandin F1 alpha from rat aortas with endothelium. In rabbit aortas, 10(-8) M PTX induced a contraction which was partially inhibited by 10(-6) M verapamil, 10(-5) M indomethacin or 10(-7) prazosin. The same concentration of PTX increased [3H]norepinephrine release from rabbit aortic adventitia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888872 TI - Analysis of putative alpha-1s adrenoceptor agonism by Sgd 101/75 in the rat anococcygeus muscle. AB - Sgd 101/75 [2-(2-methylindazol-4-imino)-imidazolidine hydrochloride] is an alpha 1 adrenoceptor agonist that shows a greater sensitivity to receptor alkylation with phenoxybenzamine (POB) than norepinephrine (NE) (present study). J. Coates, D.G. Weetman and their co-workers have concluded that Sgd 101/75 is selective for a subtype of alpha-1 receptors, i.e., alpha-1s. The present studies have shown that Sgd 101/75 was a full agonist in the rat anococcygeus muscle and acts at alpha-1 adrenoceptors, as determined by Schild analysis of prazosin antagonism (pKB = 9.24 +/- 0.21, slope = 0.87 +/- 0.13). Alkylation experiments showed that the contractile effects of Sgd 101/75 were more sensitive to POB than the effects of NE. These experiments also allowed the determination of KA values for these agonists (Sgd 101/75 KA = 1.5 +/- 0.6 X 10(-5) M, NE KA = 2.6 +/- 1.0 X 10(-6) M). At 3 X 10(-8) M POB (10 min), the contractile effect of Sgd 101/75 was eliminated, whereas the concentration-effect curve for NE was shifted approximately one log unit to the right with a 20% decrease in maximal response. After similar POB treatment, incubation with Sgd 101/75 (60 min, 3 X 10(-6) to 3 X 10(-4) M) shifted the NE curve to the right in a concentration-dependent manner. Schild regression of these data yielded a pKB = 5.22 +/- 0.09 and slope = 0.87 +/- 0.08. This pKB (-log KB) showed that Sgd 101/75 was competing for the same receptor after POB treatment and before POB treatment (mean of -log KA = 4.92 +/- 0.12).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888873 TI - ICI 147,798: a novel diuretic agent with beta adrenoceptor blocking activity. AB - ICI 147,798 is a novel compound which has both diuretic and beta adrenoceptor blocking properties in a single molecule. The natriuretic activity at 30 mg/kg p.o. was about 65% of the hydrochlorothiazide value at 10 mg/kg p.o. in saline loaded rats; the corresponding kaliuretic activity was 42%. The natriuretic and the kaliuretic activity of ICI 147,798 in dogs were similar to that of hydrochlorothiazide over the doses 1 to 20 mg/kg p.o., although significantly less kaliuresis was obtained with ICI 147,798 at 1 mg/kg p.o. In the toad bladder preparation (analogous to the distal mammalian nephron), ICI 147,798 inhibited Na+ transport with mucosal and serosal IC50 values of 56 and 120 microM, respectively. ICI 147,798 inhibited isoproterenol-induced tachycardia in rats, cats, guinea pigs and dogs; these effects were associated with antagonism of isoproterenol vasodepressor responses. The pKB values of ICI 147,798 were 9.1 and 8.8 in isolated right atria and trachea of guinea pigs, respectively. ICI 147,798 did not exhibit local anesthetic activity in rabbit cornea and intrinsic sympathomimetic activity in catecholamine-depleted dogs and rats. Duration of beta blockade after a p.o. dose of 1 mg/kg in dogs followed the sequence: nadolol greater than ICI 147,798 greater than atenolol greater than timolol greater than propranolol. It is concluded that ICI 147,798 is a novel diuretic agent with nonselective beta blockade, and it appears to have the potential of a direct tubular action. PMID- 2888874 TI - Characteristics of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine induced neurotoxicity in the mouse. AB - 1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP) was shown previously to be a more potent neurotoxicant than 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) in mice. The present investigation was conducted to determine possible reasons for the greater potency of 2'CH3-MPTP and to determine if its neurotoxic action might be similar to that of MPTP. 2'CH3-MPTP was a much better substrate for monoamine oxidase than was MPTP (Km values of 66 and 114 microM and Vmax values of 3433 and 1389 nmol/g of tissue per hr for 2'CH3-MPTP and MPTP, respectively) and it is likely that this is an important feature which contributes to its greater potency. In addition, its pyridinium metabolite, 1 methyl-4-(2'-methylphenyl)pyridinium was found to be an excellent substrate for the dopamine carrier with Km and Vmax values (513 nM and 4.1 nmol/g of tissue per min, respectively) similar to those of 1-methyl-4-phenylpyridinium (872 nM and 5.2 nmol/g of tissue per min, respectively). In vivo, 2'CH3-MPTP-induced neurotoxicity, like MPTP-induced neurotoxicity, was attenuated by the pretreatment of mice with a dopamine uptake inhibitor (mazindol or GBR 13069). However, selective doses of the monoamine oxidase (MAO)-B inhibitors, deprenyl or MDL 72145, failed to prevent in vivo neurotoxicity induced by 2'CH3-MPTP although these doses effectively blocked MPTP-induced neurotoxicity. Protection against 2'CH3-MPTP-induced neurotoxicity was observed only at a nonselective dose of MDL 72145 which blocked both MAO-B and MAO-A activities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2888875 TI - In rat hippocampus, somatostatin 14 and muscarinic receptor ligands modulate an adenylate cyclase belonging to a common domain of the receptor. AB - In hippocampal slices, somatostatin 14 and its stable analog L363 [cyclo(Phe-Pro Phe-D-Trp-Lys-Thr)] fail to modify muscarinic signal transduction mediated by stimulation of phosphoinositide breakdown, whereas somatostatin 14 mimics oxotremorine in inhibiting adenylate cyclase activity of hippocampal membranes. The simultaneous addition of somatostatin 14 and oxotremorine elicits a nonadditive convergent inhibition of adenylate cyclase activity. Both L363 and oxotremorine nonadditively stimulate a high-affinity guanosine 5'-triphosphatase activity of hippocampal membranes. This stimulation could be operative in mediating the convergent inhibition of adenylate cyclase activity elicited by the binding of specific ligands to somatostatin and muscarinic recognition sites present in hippocampal membranes. Because L363 competitively displaces muscarinic agonists fand antagonists from their specific recognition sites, one might infer that the two recognition sites interact functionally; that is, somatostatin reduces the efficacy of oxotremorine and/or vice versa. PMID- 2888876 TI - Mechanisms mediating the positive inotropic and chronotropic changes induced by dopexamine in the anesthetized dog. AB - Mechanisms contributing to the increments in heart rate (HR) and cardiac contractile force (CCF) produced by dopexamine (DPX) were studied in anesthetized dogs. Intravenous infusions of DPX (4.0 micrograms/kg/min) produced increments in HR, CCF and renal blood flow and decrements in mean arterial pressure (MAP). The sequential administration of atenolol (0.5 mg/kg i.v.) administered at a dose selective for beta-1 adrenoceptors, propranolol (2.5 mg/kg i.v.) and the DA1 dopamine receptor antagonist, SCH 23390 (10 micrograms/kg i.v.) blocked the DPX induced changes in HR, CCF, MAP and renal blood flow, respectively. After ganglionic blockade, the increments in HR and CCF produced by DPX (4.0 and 16.0 micrograms/kg i.v.) were reduced 90 and 76%, respectively, with little or no change in its hypotensive effect. In separate dogs, administration of the beta-2 adrenoceptor agonist salbutamol (0.55 microgram/kg i.v.) produced a comparable decrement in MAP but smaller increments in HR and CCF than produced by DPX (16.0 micrograms/kg i.v.). DPX (64 micrograms/kg i.v.) also produced greater increments in HR during cardioaccelerator nerve stimulation (1 Hz, 0.5 msec, supramaximal voltage) than before nerve stimulation. Therefore, we tested the effect of DPX (1.0, 4.0 and 8.0 micrograms/kg/min i.v.) on the increments in HR, CCF and MAP produced by norepinephrine (0.25 microgram/kg i.v.) and the indirect acting sympathomimetic amine, tyramine (60 micrograms/kg i.v.). DPX potentiated the increments in HR, CCF and MAP produced by norepinephrine and suppressed those produced by tyramine. Thus, the positive inotropic and chronotropic effects of DPX in the intact dog are due primarily to baroreceptor-mediated stimulation and inhibition of neuronal uptake of norepinephrine. PMID- 2888877 TI - Alpha-adrenergic inhibition of rat cerebellar Purkinje cells in vitro: a voltage clamp study. AB - 1. The effects of the alpha 2-adrenergic agonist clonidine on the membrane properties of Purkinje cells were analysed in sagittal slices of adult rat cerebellum by the use of intracellular recordings performed at a somatic level in the single-electrode voltage-clamp mode. 2. In preliminary current-clamp experiments, clonidine elicited in all cells a hyperpolarization 3-8 mV in amplitude, accompanied by a 15-35% increase of the input resistance when it was added to the bath at a concentration of 2-5 microM. 3. In voltage-clamped cells at a potential of -65 mV. the same concentration of clonidine always induced an outward shift of the holding current (0.2-0.5 nA in amplitude), thus corresponding to the hyperpolarization seen in current-clamp experiments, and this effect was accompanied by a clear increase of membrane resistance. Furthermore, clonidine markedly depressed the inward relaxations induced by hyperpolarizing commands of amplitude less than 10-20 mV whereas those induced by larger steps were much less affected. All these effects of clonidine were reversible when the drug was washed out. 4. When the slices were bathed in a medium containing 10 mM-Cs and 5 X 10(-6) M-tetrodotoxin, the inward relaxations induced by hyperpolarizing steps were abolished. However, a small inward current was still present when the membrane potential was stepped back to -65 mV, which was in turn blocked by the Ca-channel blocker Cd. This inward Ca current was also blocked by 2-5 microM-clonidine in the bath. 5. All these effects of clonidine were abolished by the alpha 1-adrenergic antagonists prazosin and phentolamine at concentrations of 0.5 and 40 microM respectively in the bath. In contrast, they were only weakly antagonized or unaffected by 2 microM of the alpha 2-adrenergic antagonist yohimbine. 6. On the basis of these results and of a previous work on the ionic basis of the inward rectification of Purkinje cells (Crepel & Penit Soria, 1986), it appears that these neurones exhibit a well developed alpha (possibly alpha 1)-adrenergic inhibition of a low-threshold Ca conductance and a Ca-dependent K conductance operating near resting potential. PMID- 2888878 TI - Quantal currents evoked by graded intracellular depolarization of crayfish motor axon terminals. AB - 1. Quantal transmitter release was examined at nerve terminals of the excitatory motor axon of the crayfish opener muscle. The magnitude of synaptic currents, recorded with macro-patch electrodes at a nerve terminal, served as a measure of quantal size. Transmitter release was initiated by pulses of depolarizing current applied intracellularly to the axonal terminals after application of tetrodotoxin. Quantal release was altered by a variety of methods and the resulting quantal output and quantal size were measured. 2. Amplitude distributions of quantal events were obtained during experimental manipulations which altered the rate of quantal release by up to 25-fold. These manipulations consisted of: varying pulse amplitude or pulse duration; facilitating the release by prolonged depolarization; and application of a potassium channel blocker, 4 aminopyridine. 3. The amplitude of quantal events is impervious to marked changes in presynaptic depolarization and is not affected by experimental procedures which promote accumulation of calcium ions in the terminals. The vesicular mechanism of release, in which transmitter substance is prepackaged in vesicles which individually undergo exocytosis at a release zone, could account for the observed results. PMID- 2888879 TI - Importance of vagal input in maintaining gastric tone in the dog. AB - 1. Using a gastric barostat to quantify variations in gastric tone, we had previously demonstrated that food ingestion or intestinal nutrient perfusion induces gastric relaxation. These data suggested a basal tonic contraction of the stomach during fasting. 2. To determine the role of vagal input in maintaining fasting gastric tone, we prepared two chronic canine models, either isolating both cervical vagal trunks in a cutaneous tunnel or including the supradiaphragmatic vagi within an implanted cooling jacket. In the fasted conscious dogs, we then studied the effect, on gastric tone, of acute and reversible vagal blockade by cooling. 3. Cervical vagal cooling produced a reversible gastric relaxation and increased the heart rate. Supradiaphragmatic vagal cooling produced a similar gastric relaxation without the cardiac effect. 4. Adrenergic blockade did not change either the base-line gastric tone or the cooling-induced relaxation. Adrenaline decreased gastric tone, but vagal cooling still produced a significant relaxation. 5. Atropine alone or combined with adrenergic antagonists produced a gastric relaxation that was not further increased by vagal cooling. Bethanechol increased gastric tone, an effect unchanged by vagal cooling. 6. We conclude that gastric tone during fasting is maintained by a cholinergic input, which is vagally mediated at both the cervical and the supradiaphragmatic levels. PMID- 2888881 TI - Parasympathetic nervous control of tracheal vascular resistance in the dog. AB - 1. The dog trachea has a copious subepithelial vasculature supplied at the cranial end by arteries from the superior thyroid artery. The parasympathetic innervation is partly in the superior laryngeal nerves, stimulation of which causes vasodilatation on both sides. 2. Section of these nerves causes a small dilatation, suggesting that there is no significant resting parasympathetic dilator tone. 3. The dilator response to nerve stimulation is about halved when atropine is given, indicating a cholinergic mechanism. 4. The residual vasodilatation on nerve stimulation in the presence of atropine is reduced but not abolished by hexamethonium, suggesting that an antidromic vasodilator pathway can be activated. 5. Stimulation of the nerves increased tracheal mucosal thickness at the same time as vascular resistance decreased. Thus vasodilator mechanisms of parasympathetic origin may contribute to tracheal mucosal swelling and hyperaemia. 6. There is considerable vascular anastomosis between the two sides of the trachea, and possibly also a crossing-over of the parasympathetic innervation. PMID- 2888880 TI - On the excitatory post-synaptic potential evoked by stimulation of the optic tract in the rat lateral geniculate nucleus. AB - 1. The electrophysiological and pharmacological properties of the excitatory post synaptic potentials (e.p.s.p.) evoked by electrical stimulation of the optic tract were studied in projection neurones of the ventral and dorsal lateral geniculate nucleus (l.g.n.) of the rat in vitro. 2. No difference was found in the rise time of e.p.s.p.s. recorded in the dorsal and ventral l.g.n. and in their threshold for action potentials. At membrane potentials more negative than 60 mV, e.p.s.p.s. in the dorsal l.g.n. were always followed by a Ca2+-dependent potential. Its amplitude could easily reach threshold for generating an action potential and thus evoke firing from an e.p.s.p. that was subthreshold at resting potential. No Ca2+ potential was observed to follow e.p.s.p.s. recorded in the ventral l.g.n. 3. At resting potential the excitability of dorsal and ventral cells was unaffected following an initial shock to the optic tract. However, in dorsal neurones, at potentials more negative than -60 mV, the presence of Ca2+ potentials evoked by the e.p.s.p.s. resulted in a period of decreased excitability. 4. Using intrasomatic injection of Cs+ the reversal potential (E) of the e.p.s.p. and of the depolarization produced by glutamate could be measured in the same l.g.n. neurone. They were: Eepsp, -0.9 mV; and Eglut, -3.9 mV. 5. gamma-D-glutamylglycine (DGG), an excitatory amino acid antagonist, reversibly inhibited the e.p.s.p. and depolarization produced by quisqualate and glutamate by a competitive action. The concentration of DGG that produced 50% inhibition (IC50) was 2.7 mM. 6. D-2-amino-5-phosphonovalerate (APV), the potent and selective N-methyl-D-aspartate (NMDA) antagonist, had no effect on the e.p.s.p. both in the presence and absence of Mg2+. The isomers of 2-amino-4 phosphonobutyrate (APB) were inactive or had a non-specific action on the e.p.s.p. 7. No difference could be detected in either the reversal potential or the action of the antagonists between neurones of the dorsal and the ventral l.g.n. 8. These results suggest that Ca2+-dependent potentials play an important role in modulating synaptic efficacy in principal neurones of the dorsal l.g.n. The quisqualate/kainate nature of the optic nerve receptors and the similarity of Eepsp and Eglut constitute strong support in favour of a glutamate-like substance as the transmitter of the optic nerve. PMID- 2888882 TI - Statistics of neuromuscular transmitter release in young and old mouse muscle. AB - 1. It was reported previously that in limb muscles of old (27-30 months) CBF-1 mice, quantal content (m) of evoked transmitter release was increased compared to that in young (9-12 months) mice. In diaphragm muscles there was no change with age. The object of the present study was to determine whether the age-related increase in transmitter release was due to increase in the binomial parameter n or the parameter p. The analysis also involved consideration of goodness-of-fit between observed and expected binomial distribution of the data. 2. Spontaneous miniature end-plate potentials (m.e.p.p.s) and evoked end-plate potentials (e.p.p.s) were recorded with intracellular techniques from soleus and diaphragm muscles bathed in low-Ca high-Mg medium. The goodness-of-fit between the observed e.p.p amplitude distribution and that expected from a binomial distribution was evaluated by chi 2 test. 3. In different muscles and at different ages, the percentage of fibres with binomial e.p.p. distributions varied from 17 to 44%, even though in all fibres there was a similar proportionality between direct quantal content and the reciprocal of the square of the coefficient of variation of e.p.p. amplitudes. In addition, apparent graphical agreement between observed and theoretical binomial e.p.p. distributions was often not substantiated by the chi 2 criterion. 4. In soleus muscles from young mice, lowering the stimulus frequency from 10 to 0.5 Hz and shortening the train length from 250 to 100 pulses increased the prevalence of binomial e.p.p. distributions, but the same result was not obtained in diaphragm or soleus muscles from old mice. If the mean amplitude of groups of 10 e.p.p.s in any train showed any drift (greater than 10%) then that train was excluded from the results. Thus, in order to make valid age comparisons, only fibres with binomial e.p.p. distributions were analysed further. 5. There was no change with age in m, n or p in diaphragm muscles, but in soleus muscles from old animals a nearly 2-fold increase in n entirely accounted for the increase in m. 6. If, as proposed by others, n represents the number of release sites, then the ageing soleus neuromuscular junction may have increased numbers or length of active zones or associated membrane components. PMID- 2888883 TI - Contributions of inhibitory mechanisms to the shift responses of X and Y cells in the cat lateral geniculate nucleus. AB - 1. Adult cats were anaesthetized with a mixture of halothane, nitrous oxide and oxygen to record from single neurones of the dorsal lateral geniculate nucleus (d.l.g.n.) with five-barrel glass micro-electrodes. Periphery effects (shift effects) were elicited by large-field phase-reversing gratings presented in the visual field outside the conventional receptive field area. 2. A range of transient excitatory responses was found in X and Y cells. Y cells had phasic shift effects with significantly higher amplitudes and shorter durations (mean 52 impulses/s, 135 ms) than those observed in the tonic shift effects of X cells (mean 24 impulses/s, 169 ms). All Y cells and most X cells responded to stimulation of remote retinal regions. About 7% of the X cells displayed no shift effect. 3. Micro-ionophoresis of the gamma-aminobutyric acid (GABA) antagonist bicuculline, acetylcholine (ACh) and L-glutamate specifically influenced the shift effects of X and Y cells. 4. During continuous application of the GABA antagonist bicuculline the differences in maximal response rates and amplitudes of X and Y cells were eliminated. The maintained activity raised predominantly in X cells and the early peak rates increased more in X- than in Y-cell shift effects, leading to equal average peak rates of 100 and response amplitudes of about 85 impulses/s in both cell classes. The characteristic time courses of X- and Y-cell responses were not affected. 5. Micro-ionophoretic application of ACh caused a combination of excitatory and disinhibitory effects. Maintained activity as well as early parts of stimulus-evoked responses were similarly raised in X and Y cells. In addition, the Y-cell shift effects became less phasic by elevation of the late response part. Sodium pentobarbitone, used to block ACh excitation, suppressed the ACh-induced effects in the early phase of the X- and Y cell shift effects and the increase of maintained activity in Y-cells, while the effect on the late part of Y-cell responses persisted. Elevation of background activity partially remained in X cells, and the X-cell responses became tonically prolonged at the same time. 6. L-Glutamate increased the activity of X and Y cells without changing the characteristic shift-effect properties of both cell classes. 7. It is concluded that different short- and long-lasting inhibitory mechanisms shape the responses of d.l.g.n. neurones to stimulation outside the conventional receptive field.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2888884 TI - Influence of depolarizing pulse duration on the time course of transmitter release in lobster. AB - 1. Experiments have been made at lobster neuromuscular synapses to study synaptic delays and in particular the phenomenon known as 'latency shift'. Earlier work had suggested that synaptic delay becomes prolonged when pulses of long duration are applied to presynaptic terminals. 2. By observing single quanta, prolonged depolarizing pulses at low and moderate amplitudes have been shown to shift the peak of the synaptic delay histogram. There is however no increase in the minimal delay. 3. The apparent differences between these and earlier results have been shown to depend on differences in experimental procedures. In particular, in the present study equal numbers of pulses are applied at the various pulse durations and the number of quanta that had been released is presented. PMID- 2888885 TI - The secretory actions of histamine in rat small intestine. AB - 1. Histamine caused a dose-dependent rise in the transintestinal potential difference in vivo that was competitively blocked by H1, but not by H2 antagonists. This effect of histamine was also reduced by the cyclo-oxygenase inhibitor indomethacin. 2. Histamine induced a net secretion of fluid by the small intestine and this effect was reduced by indomethacin. 3. In intestinal sheets histamine increased the potential difference, short-circuit current and tissue resistance. This response was decreased in the absence of Cl- and in the presence of furosemide, suggesting that Cl- secretion was responsible for the observed electrical changes. This was confirmed by direct measurement of ion fluxes which showed an increase in net Cl- secretion together with an inhibition of net Na+ absorption. 4. The response to histamine was Ca2+-dependent since it was inhibited by removal of serosal Ca2+ and by verapamil. 5. Indomethacin caused a dose-dependent reduction in the response of intestinal sheets to histamine, without affecting the rise in short-circuit current induced by mucosal glucose or serosal prostaglandin E2. Mepacrine also inhibited the response to histamine, but not that to prostaglandin E2. 6. It is concluded that histamine induces intestinal secretion by stimulating the production of prostaglandins which then activate the secretory process. PMID- 2888886 TI - A fast electrophoretic isoenzyme technique for the identification of invasive and non-invasive Entamoeba histolytica and "E. histolytica-like" organisms. AB - Cellulose acetate electrophoresis (CAE) was used to separate glucosephosphate isomerase, hexokinase, malic enzyme, and phosphoglucomutase extracted from invasive and non-invasive Entamoeba histolytica and "E. histolytica-like" organisms. Each of these morphologically similar organisms possessed a unique CAE isoenzyme profile that can be used as an aid in their identification. The CAE technique used to obtain these isoenzyme profiles is rapid, simple, and economical, and it requires neither specialized training nor elaborate equipment. PMID- 2888887 TI - Application of free tissue transfers to the foot. AB - During the past five years we have used three sources of free tissue transfers in 26 patients to reconstruct defects of the ankle and dorsum, hind, mid- and forefoot, defects poorly or unamenable to traditional reconstructive methods. These included free muscle transfers covered with a skin graft, temporoparietal fascia also covered with a graft, and radial forearm skin or fascia. In addition, six complex defects were reconstructed with composite tissue free transfers, usually tendinocutaneous flaps. There was one partial flap loss. All were successful in both healing the defect and in providing functional restoration, except in the forefoot. From an analysis of these cases, we have developed indications for various transfers based on the functional needs of the area involved and donor site requirements. PMID- 2888888 TI - Psychological treatment for benzodiazepine dependence. PMID- 2888889 TI - Identification and characterization of specific binding sites for somatostatin in cytosol of bovine cystic duct mucosa. AB - Specific binding sites for somatostatin have been detected in cytosolic fraction of bovine cystic duct mucosa. At 37 degrees C, the interaction of 125I-Tyr11 somatostatin with cytosolic fraction was rapid, reversible, specific and saturable. At equilibrium, the binding of tracer was competitively inhibited by native peptide in the 1 nM to 2 microM range of concentrations. Scatchard analysis of binding data suggested the presence of two distinct classes of somatostatin binding sites: a class with a high affinity (Kd = 7.8 +/- 0.3 nM) and a low capacity (1.3 +/- 0.3 pmol somatostatin/mg protein) and a class with a low affinity (Kd = 129.1 +/- 2.0 nM) and a high capacity (43.5 +/- 6.7 pmol somatostatin/mg protein). The binding sites were shown to be highly specific for somatostatin since neuropeptides present in cystic duct such as Leu-enkephalin, neurotensin, substance P and vasoactive intestinal peptide did practically not show competition. These findings suggest that somatostatin could contribute to the regulation of the functions of the cystic duct mucosa in physiological and pathological conditions. PMID- 2888890 TI - Similarity of central and peripheral alpha-1 adrenoceptors in rat and rabbit. AB - In order to examine species and tissue differences in alpha 1 adrenoceptors, binding experiments were performed using 3H-prazosin and membrane homogenates of central nervous and peripheral tissues of rabbit (cortex and spleen), and rat (cortex, spleen, and liver). Saturation studies indicated one binding site for 3H prazosin, with apparent log molar dissociation constants (pKD) ranging from 9.43 to 10.20. The rank orders of affinities of three competing antagonists (prazosin much greater than idazoxan greater than rauwolscine) and five agonists (cirazoline greater than clonidine approximately equal to (-)-norepinephrine greater than (-)-phenylephrine greater than (+)-norepinephrine) were typical of alpha 1 receptors in all tissues. There were small but significant differences in the mean affinities of rauwolscine, idazoxan and cirazoline among the five tissues. No significant differences in pseudo-Hill coefficients were observed among tissues, although agonist binding curves were shallow (.7 to .85) and prazosin competition curves were significantly steeper (greater than .85). Guanine nucleotide did not affect the position or slope of the (-)-norepinephrine competition profile in rat cortex. These results demonstrate a qualitative similarity among central and peripheral alpha 1 receptors of the rat and rabbit, with small differences observed between central and peripheral sites in both species. PMID- 2888891 TI - Routine use of beta-blockers following myocardial infarction: a note of dissent. PMID- 2888892 TI - Small bowel ischemia due to necrotizing vasculitis following serous otitis media. PMID- 2888893 TI - Principles of DNA-based prenatal diagnosis of cystic fibrosis: an introduction for the clinician. PMID- 2888894 TI - N6-(2,2-diphenylethyl)adenosine, a novel adenosine receptor agonist with antipsychotic-like activity. PMID- 2888895 TI - Studies on histamine H2 receptor antagonists. 2. Synthesis and pharmacological activities of N-sulfamoyl and N-sulfonyl amidine derivatives. AB - A series of N-sulfamoyl and N-sulfonyl amidines have been prepared and tested in vitro for H2 antihistamine activity on guinea pig atrium. In addition, several selected compounds were assessed as inhibitors of gastric acid secretion induced by histamine in anesthetized dogs. Structure-activity relationship studies showed that those compounds containing 2-[(diaminomethylene)amino]thiazole exhibited potent H2-receptor antagonist activity. Introduction of alkyl or aralkyl groups to the terminal nitrogen of the sulfamoyl moiety reduced biological activities. Sulfamoyl amidines were more potent in both tests than sulfonyl amidines. Of these compounds, 3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]- N2 sulfamoylpropionamidine (2e, famotidine) showed extremely high potency in both assays and was selected for clinical trials as an antiulcer agent. Acid-catalyzed hydrolysis of famotidine gave the sulfamoyl amide 6 at room temperature and the carboxylic acid 7 at elevated temperatures. 15N NMR spectrum showed that famotidine in solution existed in only one of several possible tautomers derived from the amidine and the guanidine moieties. Nitrosation of famotidine was performed under mild condition and proved to occur on the 5-position of the thiazole ring. PMID- 2888896 TI - 2,4-Diamino-6,7-dimethoxyquinazolines. 3. 2-(4-Heterocyclylpiperazin-1-yl) derivatives as alpha 1-adrenoceptor antagonists and antihypertensive agents. AB - A series of 4-amino-6,7-dimethoxy-2(4-heterocyclylpiperazin-1-yl)quinazolines (3) was prepared and screened for alpha-adrenoceptor affinity and antihypertensive activity. These quinazoline derivatives showed high binding affinity (ca. 10(-10) M) and selectivity (greater than 10,000) for alpha 1-adrenoceptors in vitro, with no relevant activity at alpha 2 sites. Several compounds displayed similar activity to prazosin (Ki = 1.9 X 10(-10) M) while the dimethoxytriazine derivative 30 (Ki = 8 X 10(-11) M) was more potent. Like prazosin (pA2 = 8.37 +/- 0.24), 30 proved to be a potent (pA2 = 8.63 +/- 0.15), competitive antagonist of the alpha 1-mediated vasoconstrictor action of norepinephrine. The high binding affinity of series 3 is most likely due to formation, at physiological pH, of the protonated, alpha 1-adrenoceptor pharmacophore 33, coupled with efficient hydrophobic interactions of the quinazoline 2-substituents. Computer-assisted super-imposition of prazosin and 30 showed little structural correspondence between the furoyl and dimethoxytriazine moieties, and specific interactions of these molecular fragments with the receptor protein appear unlikely. Series 3 was evaluated for antihypertensive activity after oral administration (5 mg/kg) to spontaneously hypertensive rats, and blood pressure was recorded after 1 and 6 h. In vivo performance was markedly dependent on the nature of the distal heterocyclic system and various derivatives demonstrated superior or equivalent profiles to prazosin, with respect to both antihypertensive efficacy and duration of action. PMID- 2888898 TI - Antipsychotic activity of substituted gamma-carbolines. AB - Several novel substituted gamma-carbolines were synthesized and examined in a series of in vitro and in vivo pharmacological tests to determine potential antipsychotic activity. Most compounds were orally active in blocking the conditioned avoidance response (CAR) in rats but did not antagonize apomorphine induced stereotyped behavior. Compound 17 (Wy-47,384), a gamma-carboline with a 3 (3-pyridinyl)propyl side chain, was selected for development as an atypical antipsychotic agent because of its potent and selective profile in preclinical psychopharmacological tests. It blocked CAR in rats with an AB50 of 14 mg/kg po, showed weak affinity for the D2 receptor site (Ki = 104 nM), and showed differential potency in antagonizing apomorphine-induced stereotyped behavior (ED50 = 11 mg/kg ip) and climbing behavior (ED50 = 4 mg/kg ip). Such activities are suggestive of antipsychotic efficacy combined with a low potential for extrapyramidal side effect (EPS) liability. PMID- 2888897 TI - 1,3-Dialkyl-4-(iminoarylmethyl)-1H-pyrazol-5-ols. A series of novel potential antipsychotic agents. AB - 2-(Diethylamino)-N-[4-(2-fluorobenzoyl)-1,3-dimethyl-1H-pyrazol-5-yl] acetamide (1) was recently found to have an antipsychotic-like profile in behavioral animal tests but, unlike clinically available antipsychotic agents, did not interact with dopamine receptors. Compound 1 was apparently metabolized to (5-amino-1,3 dimethyl-1H-pyrazol-4-yl)(2-fluorophenyl)methanone (2), which was both active in the behavioral animal tests and toxic. The synthesis and pharmacological evaluation of a series of 1,3-dialkyl-4-(iminoarylmethyl)-1H-pyrazol-5-ols are described in which the hydroxy and imine functionalities were selected as possible isosteric replacements for the amino and ketone groups of the earlier series. The initial target, 1,3-dimethyl-4-(iminophenylmethyl)-1H-pyrazol-5-ol (28), like known antipsychotics, reduced spontaneous locomotion in mice at doses that did not cause ataxia, and unlike known agents, it did not bind to D2 dopamine receptors in vitro. An examination of the SAR of related compounds indicated that maximal activity was obtained with analogues containing methyl groups at the 1- and 3-positions on the pyrazole ring and with a 3-chloro substituent on the phenyl ring. Replacement of the hydrogen atom of the imine moiety with various substituents led to loss of activity. Attempts to synthesize the 2-fluorophenyl compound analogous to 2 resulted in ring-closure to 1,3 dimethyl[1]benzopyrano[2,3-c]pyrazol-4-(1H)-one (65). 4-[(3 Chlorophenyl)iminomethyl]-1,3-dimethyl-1H-pyrazol-5-ol (41) was evaluated in additional tests. It inhibited conditioned avoidance responding in both rats and monkeys but, unlike available antipsychotic drugs, did not elicit dystonic movements in a primate model of antipsychotic-induced extrapyramidal side effects. PMID- 2888899 TI - Combined analgesic/neuroleptic activity in N-butyrophenone prodine-like compounds. AB - Some 4-phenyl-4-piperidinols, corresponding esters, and related compounds with a p-fluorobutyrophenone chain on nitrogen were synthesized and evaluated in in vitro and in vivo tests in order to examine their ability to interact contemporaneously with opioid and dopamine receptors. The propionyloxy derivatives showed a good combination of analgesic and neuroleptic activity. With a 3-methyl substituent on the piperidine ring, the beta-configuration was the more active form not only for analgesic activity, as expected from previous results on prodines, but also for neuroleptic activity. Haloperidol and its propionate were also tested as reference compounds. PMID- 2888900 TI - A computerized information management system for educational programs in the health sciences. AB - The Physician Assistant Program at the University of Florida has developed and implemented a computerized information management system that eliminates time consuming duplication of effort in record-keeping and covers all functional components of the educational program. Data-base files for admissions, curriculum and/or evaluation design, student records, graduate follow-up, and research activities and a master file for administrative activities permit rapid accessing and transfer of information across files, continual updating of information, and efficient generating of records and reports pertaining to all program functions. Research about the program is enhanced through the correlation of data available in the five data-base files. This comprehensive system facilitates the audit of the program's educational process and the evaluation of its accomplishment of its stated objectives. The system can be easily adapted for use by other educational programs in medicine and the allied health sciences. PMID- 2888901 TI - The recent evolutionary origin of the phenylalanine-sensitive isozyme of 3-deoxy D-arabino-heptulosonate 7-phosphate synthase in the enteric lineage of bacteria. AB - Evolutionary events that generated the three regulatory isozymes of 3-deoxy-D arabino-heptulosonate 7-phosphate (DAHP) synthase present in contemporary strains of Escherichia coli have been proposed recently [Ahmad et al. (1986) J Bacteriol 165:146-154]. The phylogenetic subdivision of gram-negative prokaryotes studied (Superfamily B) includes enteric bacteria, an Oceanospirillum cluster, pseudomonad Group I (e.g., Pseudomonas aeruginosa), pseudomonad Group V (e.g., Xanthomonas), and the Acinetobacter grouping. DAHP synthase-phe, a regulatory isozyme subject to allosteric control by L-phenylalanine, was the last member of the isozyme family to evolve. Thus, DAHP synthase-phe is absent throughout Superfamily B except within the enteric lineage. Bacteria that make up the enteric lineage (Escherichia, Klebsiella, Erwinia, Serratia, Proteus, Aeromonas, and Alteromonas) were examined in detail; DAHP synthase-phe was present in each of these organisms. Therefore, the isozyme originated between the separation of the enteric and Oceanospirillum lineages, prior to the divergence of Alteromonas putrefaciens (44% homology with E. coli by DNA:rRNA hybridization) from the rest of the enteric lineage. DAHP synthase-tyr and DAHP synthase-trp were uniformly present within the enteric lineage, although it was often necessary to derepress DAHP synthase-trp by physiological manipulation in order to demonstrate its presence. PMID- 2888902 TI - Antinociceptive actions of intravenous alpha 2-adrenoceptor agonists in sheep. AB - The antinociceptive activity of the intravenously administered alpha 2 adrenoceptor agonists, clonidine and xylazine, was measured in sheep using thermal and mechanical pressure threshold detection systems. Both drugs demonstrated clear antinociceptive activity for both forms of threshold stimuli and clonidine at 6 micrograms/kg i.v. was more potent and longer lasting than xylazine at 50 micrograms/kg i.v. The antinociceptive effects were reversed by idazoxan (0.1 mg/kg i.v.), but were not affected by naloxone at 0.2 mg/kg i.v. indicating that these effects were mediated by alpha 2-adrenoceptors. PMID- 2888903 TI - The role of vasoactive intestinal polypeptide as a neurotransmitter in canine penile erection: a combined in vivo and immunohistochemical study. AB - Vasoactive intestinal polypeptide (VIP), a 28-amino-acid polypeptide found in the human gut and genitourinary tract, primarily affects vasodilation and smooth muscle relaxation. These effects have led to speculation that this neuropeptide may be a neurotransmitter in certain bodily functions, such as penile erection. We therefore designed an in vivo animal model to elucidate the influence of VIP and VIP antibody on the different stages of penile erection. We also performed immunohistochemical studies of the penile tissue to obtain further information about the distribution of VIP in the corpora cavernosa. Intracavernous injection of VIP induced penile erection. Its effect on arterial inflow was minor, but it caused active venous outflow restriction and was important in maintaining erection. VIP antibody blocked venous outflow restriction during neurostimulation induced erection. VIP was found in the cavernous tissue (in the area between the smooth-muscle cells and the sinusoidal spaces) in close proximity to the arteries. We conclude that VIP is a neurotransmitter in the erectile tissue of the penis, and that its effects are similar to those from electrostimulation of the cavernous nerve. VIP increases arterial flow, decreases venous flow, and induces sinusoidal relaxation. PMID- 2888904 TI - Magnetic resonance imaging in genital anomalies. AB - Magnetic resonance imaging, a new radiographic modality that is not dependent on ionizing radiation or intravenous contrast agents, was used to identify undescended testes in 11 patients. Of 14 undescended testes 13 were identified and the only testis that was not seen was in a patient with surgically proved unilateral anorchism. We also used magnetic resonance imaging in 9 patients with various types of intersex. The anatomy of the corpora cavernosa, vagina, uterus and gonads was well seen in each instance. PMID- 2888905 TI - Long-term effect of luteinizing hormone-releasing hormone analogue (buserelin) on cryptorchid testes. AB - We studied 48 prepubertal boys with cryptorchidism between 1 year 3 months and 11 years old who were treated with buserelin every other day for 6 months. Urinary luteinizing and follicle-stimulating hormones, and testosterone remained unchanged during the entire treatment period. In boys older than 7 years a slight but significant increase in testosterone was noted in the first morning voided urine at the end of treatment. Testicular biopsies were obtained at orchiopexy in all patients in whom testicular descent was not complete (83 per cent). A significant increase in the number of germ cells was observed in patients with unilateral and those with bilateral cryptorchidism, indicating that 6 months of buserelin therapy improved the fertility status even when testes were in an undescended position during treatment. PMID- 2888906 TI - Fertility in cryptorchidism: improved timing of fixation and treatment in an experimental model. AB - Modifications were made in an experimental model in the rat to make it more analogous to human cryptorchidism and more useful in evaluating treatment. The age of experimental bilateral cryptorchidism was changed from 3 days to 11 days. Neither group was able to father offspring. The age at orchiopexy also was modified from the range of 21 to 28 days to exactly 21 days. The ability to father offspring improved significantly (72 versus 30 per cent) and it was not significantly different from previously reported sham operated rats (84 per cent). The current experimental model demonstrates that early surgical treatment can restore fertility to mechanically cryptorchid animals. The model can be used to evaluate the effects of varying types and timing of treatment. PMID- 2888907 TI - Neuroscience, AIDS head agenda at AMA-NY Hospital-Cornell conference. PMID- 2888908 TI - Treatment of external gastrointestinal fistulas by a combination of total parenteral nutrition and somatostatin. AB - Thirty-seven patients with external gastrointestinal fistulas were treated with a combination of total parenteral nutrition (TPN) and somatostatin (ST). There was a significant fall in fistula output within the first day of treatment (p less than 0.001). On the first day of combined therapy, the reduction of fistula output was 70%, and in 68% of the cases, the fistula output fell to less than 50% of the initial level. Spontaneous closure was observed in 82% of the cases, and the time taken to close the fistula ranged between 1 and 14 days of starting therapy [5.4 +/- 0.7 days (mean +/- SEM)]. The response to TPN-ST treatment occurred, irrespective of age and sex of patients, duration and daily output of the fistulas before ST use, and their location in the gastrointestinal tract. Infection of fistula output was a factor of adverse prognosis. In all cases, and in the absence of mechanical obstacles, treatment that combines TPN and ST could be tried and continued up to 14 days in cases in which the fistula output falls more than 50% on the first day of treatment. PMID- 2888909 TI - [Comparative studies on hemodynamic effects of intravenous cimetidine, ranitidine and famotidine in intensive care unit patients]. PMID- 2888910 TI - [Immunology in obstetrics. 5. Immunity in perinatal infections (3): Current topics on viral infections--AIDS and ATL (adult T-cell leukemia)]. PMID- 2888911 TI - [Impression on the 22nd Congress of the Japanese Medical Society: with special reference to the Nursing Symposium]. PMID- 2888912 TI - [The 22nd Congress of the Japanese Medical Society: a nursing student's view]. PMID- 2888913 TI - [Reflection on the annual general meeting of the Japanese Association of Nursing: a thought as a member of a giant professional organization: hope for democratic organization and management]. PMID- 2888914 TI - [Impression on the general meeting of the Japanese Association of Nursing: discussion of the keypoints of the 1987 meeting of the association]. PMID- 2888915 TI - Characterization of the activity of a platelet activating factor antagonist, CV 3988. AB - CV-3988 inhibited the vascular permeability increase induced by C16-PAF and C18 PAF in rat skin in a dose-dependent manner. The inhibition was shown to be specific and competitive with PAF on its receptor by the following observations: parallel shift of the dose-response curve; crossing of double reciprocal plots on the intersection of the ordinate; and no inhibition on other autacoids such as bradykinin, histamine, 5-hydroxytryptamine and LTC4. PAF-induced blood pressure fall in rats was also suppressed by pretreatment with CV-3988 selectively. PMID- 2888916 TI - Effects of nipradilol, a new beta-adrenoceptor blocking agent with vasodilating properties, on transmural energy metabolism in the underperfused canine heart. AB - Effects of nipradilol on hemodynamics and transmural energy metabolism of underperfused (ischemic) canine hearts were investigated. The ischemic heart was prepared by constricting a tube connecting the circumflex coronary artery with the carotid artery for 10 min so that the perfusion pressure (CPP) was reduced to 30 mmHg. The reduction in CPP resulted in decreases in coronary blood flow (CBF) by 70%, regional myocardial contractile force (MCF) by 30%, myocardial ATP contents by 32% (inner layer)-22% (outer) and creatine phosphate by 75% (inner) 60% (outer). Increases in the left ventricular end diastolic pressure (LVEDP) by 4.8 mmHg, myocardial inorganic phosphate contents by 1.9 times (inner)-1.3 (outer) and lactate by 4.3 times (inner)-2.4 (outer) were also observed. In dogs with normal hearts, an infusion of nipradilol (10 micrograms/kg/min, i.v., for 15 min) decreased CPP by 25%, CBF by 40%, cardiac effort index by 45% and MCF by 30 to 40%, and it slightly increased LVEDP without affecting myocardial high-energy phosphate and lactate levels. In ischemic hearts, nipradilol infusion starting 5 min before ischemia attenuated the ischemia-induced elevation of LVEDP to 1.8 mmHg, and the ischemia-induced changes in high-energy phosphate contents to 1/2 (inner)-1/3 (outer) and changes in lactate to 1/6 (inner)-1/10 (outer). These results indicate that nipradilol improves the ischemic derangement of both transmural energy metabolism and hemodynamics. PMID- 2888917 TI - In vitro characterization of alpha-adrenergic receptor in rabbit detrusor muscle. AB - In the isolated detrusor smooth muscle of the rabbit urinary bladder, acetylcholine, prostaglandin (PG) F2 alpha, histamine and methoxamine produced dose-dependent contractions. The order of efficacy was acetylcholine greater than PGF2 alpha greater than histamine greater than methoxamine. Acetylcholine and oxotremorine increased tension remarkably in the rabbit detrusor muscle; and McN A-343 also developed tension, but with weaker sensitivity and efficacy. The contractile response to acetylcholine was competitively antagonized by atropine (pA2 9.24) and pirenzepine (pA2 6.96), respectively. Histamine and 2 pyridylethylamine caused dose-dependent contractions. On the other hand, dimaprit caused no response in this tissue. Mepyramine (pA2 8.80) competitively antagonized the contraction induced by histamine, whereas cimetidine failed to antagonize the contraction even at a high concentration of 10(-5) M. Norepinephrine, phenylephrine and methoxamine have greater efficacies in the ability to contract than clonidine. R(-)- and S(+)-YM-12617 and YM-12617 (pA2 10.4, 8.31 and 9.75, respectively) and prazosin (pA2 8.13), phentolamine (pA2 7.55) and yohimbine (pA2 6.44) competitively antagonized the contraction elicited by methoxamine. These results suggest that the contraction of rabbit detrusor muscle can be mediated by alpha 1-adrenergic receptors as well as M2-muscarinic and H1-histaminergic receptors and suggest that the contractile force mediated by alpha 1-adrenergic receptor agonist is smaller than those stimulated by the other receptor agonists. PMID- 2888918 TI - Potentiating effect of tyramine on acetaldehyde-induced vasoconstriction in isolated dog mesenteric arteries. AB - The stainless steel cannula inserting method was used to investigate the effects of acetaldehyde on isolated and perfused dog mesenteric arteries. Acetaldehyde when intraluminally administered induced a marked vasoconstriction, but repetitive injections of acetaldehyde caused tachyphylaxis. Acetaldehyde-induced vasoconstrictions were blocked by bunazosin, an alpha-1 adrenoceptor antagonist. After tyramine treatment, the acetaldehyde-induced constriction was consistently restored temporarily. It is suggested that tyramine may induce a release of norepinephrine mostly from the vesicle to the neuronal cytosol, and acetaldehyde may cause a release of norepinephrine from the cytosol to the extracellular space in the isolated canine mesenteric artery. PMID- 2888919 TI - [Appearance of ATL cell and ATLA-related reactions in diffuse panbronchiolitis]. PMID- 2888920 TI - [Appearance of ATLA-related reactions and ATL-like cells in idiopathic interstitial pneumonia]. PMID- 2888921 TI - [Preventive measures against intractable asthma--from a behavioral point of view]. PMID- 2888922 TI - [Biofeedback therapy of bronchial asthma]. PMID- 2888923 TI - [Aorto-arteritis (Takayasu disease) in clinical picture]. PMID- 2888924 TI - Prostaglandin-E2 receptors in the rat kidney: biochemical characterization and localization. AB - A radiohistochemical technique yielding data on the distribution and characteristics of PGE2-receptor binding in tissue sections is described. The binding of tritiated PGE2 (3H-PGE2) to slide-mounted tissue sections had all the characteristics associated with ligand-receptor interactions: it was saturable, of high affinity and displayed high specificity for PGE2 binding. From the binding curves a Hill coefficient of 1.1 was calculated which suggests the presence of a homogeneous receptor population. Pretreatment with indomethacin for four days resulted in a 66% increase in maximal binding capacity (Bmax) without any change in affinity. The distribution of receptor was mapped in rats with and without indomethacin pretreatment and compared to the distribution of Tamm Horsfall glycoprotein, a specific marker for the thick ascending limb of Henle. In both groups the PGE2 receptor showed striking regional variation. In the untreated group the distribution of PGE2 receptors was similar to that of the thick ascending limb of Henle, with maximal density in the outer medullary zone. After indomethacin pretreatment, however, a striking increase in inner medullary binding was observed together with increased binding in the cortex. Thus, in accordance with the main action of PGE2 being regulation of renal water and sodium excretion, we found the highest receptor density in areas of the kidney dominated by the thick ascending limb of Henle and collecting tubules, and much less binding to glomeruli and cortical vessels. In order to investigate characteristics and distribution of PGE2 receptor binding, however, it was mandatory that endogenous prostanoid synthesis is blocked. PMID- 2888925 TI - [Physiologic and immunologic aspects of the adaptation of man to increased heat exposure in an enclosed environment]. AB - Physiological and immunological investigations have shown that on day 2 of adaptation to the warming enclosed environment the test subjects may develop pustular skin disease. A certain role in the disease is played by the autoinfection process aggravated by sensitization of the organism to autoantigens. PMID- 2888926 TI - Probability of quantal transmitter release from nerve terminals: theoretical considerations in the determination of spatial variation. AB - The release of transmitter occurs in discrete quantal units, such that the number released (m) is equal to the number available (n) times the average probability of release (p). Although a common method of estimating these parameters is to use simple binomial statistics, results may be biased if there is spatial or temporal variation in n and p (vars p, vart n, vart p). The problem arises in the simultaneous analysis of five variables, which is impractical due to the complexity and margin of error involved. The proposed solution is to eliminate two variables (vart n, vart p) by assuming stationarity and to obtain the required information from the first three moments of m. The resulting quadratic equation gives two solutions, p1 and p2. Computer simulation of quantal output as a function of vars p indicates that p1 is the better estimator of p when vars p is small, but that p2 is better when vars p is large. This changeover or "inflection" occurs at points which correspond to the maximum vars p obtainable by unimodal distributions of p (larger vars p being obtained by bimodal distributions). Comparison of the simulated histogram of m with those predicted by p1 and p2 shows that p1 provides the better fit, whether vars p is large or small. This discrepancy indicates that histogram analysis is unable to distinguish the appropriate estimate. The major limitations in the procedure can be met by assuming (1) stationarity (which can be attained and tested experimentally), and (2) normal distribution of p (since vars p is then less than "inflection" point, p1 will always be the correct estimate). The overall findings demonstrate that vars p and unbiased estimates of n and p may be calculated, provided reasonable assumptions are made. This in turn should allow the continued use of quantal parameters for describing transmitter release. PMID- 2888927 TI - Mechanisms of alcohol withdrawal syndrome. AB - The basic mechanism or mechanisms of the alcohol withdrawal syndrome (AWS) are still unknown despite extensive research on alcoholism. There are, however, two major hypotheses or groups of hypotheses. Increasing experimental evidence supports adaptive changes in membrane lipids and/or proteins in response to prolonged high alcohol concentrations which might cause abnormal function after withdrawal of alcohol in general or more specifically in certain receptor sites. Changes in the formation or concentration of some receptor ligands as a consequence of alcohol metabolism are, however, also possible. Both can cause changes in neurotransmission, and these have been found in several systems. Although all studies do not agree, there seems to be some reduction in gabaergic, enkephalinergic, and possibly in dopaminergic function and increase in glutaminergic, adrenergic, cholinergic and possibly in serotoninergic and tryptaminergic activity at least in some neurons during AWS. These may be involved in producing some symptoms, but the variable whole AWS, particularly its two phases, remains to be explained. PMID- 2888928 TI - Cerebral monoamine neurotransmitters in opioid withdrawal and dependence. AB - The functioning of cerebral monoaminergic neurons is altered during withdrawal from morphine. Our results suggest that the functioning of cerebral dopaminergic and possibly 5HTergic neurons might be regulated by opioid mechanisms and these neurons may be important in the reinforcing and rewarding effects of morphine. The limbic dopaminergic neurons seem to be more vulnerable to chronic opioid administration than the striatal ones. The cerebral noradrenergic neurons seem to be linked with physical signs and symptoms of opioid withdrawal. PMID- 2888929 TI - Aminergic regulation of neuroendocrinological functions: theoretical background and some clinical examples. AB - Remarkable progress has been made during recent years in the central regulation of the hypothalamic releasing and inhibiting factors and the respective anterior pituitary hormones. There are two nearly universal inhibitory organizations: short tuberoinfundibular dopamine (TIDA) neurons and somatostatinergic system originating from the periventricular hypothalamus and terminating to the median eminence. It is now known that e.g. dopamine, noradrenaline and acetylcholine enhance while 5-hydroxytryptamine and GABA inhibit somatostatin secretion. These transmitters are also involved in the regulation of all releasing factors and pituitary hormones. Clinical applications have been developed based on the regulation of prolactin and growth hormone. Inhibitory TIDA neurons are undoubtedly the major determinants of prolactin secretion. Hyperprolactinaemia is one of the most common endocrinological side-effects of the drugs antagonizing dopaminergic transmission. Expectedly, dopaminergic drugs (bromocryptine, lergotrile, piribedil, dopamine and levodopa) are quite effective in reducing high prolactin levels regardless of the reason. The secretion of growth hormone is predominantly under dual dopaminergic control: hypothalamic stimulation and pituitary inhibition. The former masters the function of the normal gland, while the peripheral inhibitory component takes over in acromegalic gland. Hence dopaminergic drugs are able to reduce elevated growth hormone levels in 30-50% of the acromegalic patients. In normal man, dopamine agonists increase growth hormone levels. An analogous situation can be seen in Cushing's disease regarding ACTH secretion. PMID- 2888930 TI - Neurochemical aspects of amino acid transmitters and modulators. AB - The presynaptic and postsynaptic actions of amino acid transmitters gamma aminobutyrate, glutamate, aspartate and glycine in the central nervous system are reviewed. PMID- 2888931 TI - Protection against hypoxic/ischaemic brain damage with excitatory amino acid antagonists. AB - Selective neuronal loss in the hippocampus following transient forebrain ischaemia appears to be excitotoxic in origin. The early cytological changes in the rat hippocampus (1-2 hours after 10 or 30 minutes of ischaemia) have the ultrastructural appearances of an excitotoxic lesion. Focal injection of an excitatory amino acid antagonist acting competitively on the N-methyl-D-aspartate (NMDA) receptor, 2-amino-7-phosphonoheptanoic acid (2-APH) in one hippocampus protects against the early cytopathology, and, when repeated 4 and 10 hours after the ischaemia, partially protects against selective nerve cell loss. Systemic administration of 2-APH or of a non-competitive antagonist at the NMDA receptor, ketamine, also protects against neuronal loss. Blockade of excitatory transmission at the NMDA receptor may provide a therapeutic approach to the acute treatment of cerebral ischaemia. PMID- 2888932 TI - GABA-benzodiazepine receptor complex and drug actions. AB - This short review describes the benzodiazepine receptors, their interplay with GABAergic transmission and chloride ionophore, the search for endogenous ligands, and the drug responses that can be evoked through these receptors. Benzodiazepine receptors offer a unique pathway through which opposite drug actions e.g., anxiogenic and anxiolytic effects can be exerted, and these actions can be inhibited with competitive receptor antagonists. The most plausible endogenous ligand for benzodiazepine receptors discovered so far, a polypeptide DBI, exerts actions opposite to those of the benzodiazepines used in clinical therapy. This has been the stimulus for a new look at the physiological role for these receptors. PMID- 2888933 TI - Chemical neurotransmission in the central nervous system as a target for drug treatment. Proceedings of a symposium. Helsinki, January 5-6, 1987. PMID- 2888934 TI - Monoaminergic mechanisms in affective disorders. AB - The monoamine hypothesis of depression originally proposed that depression is caused by a central deficiency of biogenic amines, and antidepressants were considered to work by correcting this deficiency. In the course of time, many studies have analysed monoamine metabolites in the urine, plasma and cerebrospinal fluid of patients and healthy controls under different conditions to test the hypothesis. These studies have failed to identify a robust metabolic disorder in depressive patients as a group. Certain subgroups of depressed patients have shown deviations in biogenic amine metabolism, the most consistent being reduced levels of the major serotonin and dopamine metabolites in the cerebrospinal fluid. Noradrenaline metabolism is influenced by the activity of the sympathetic nervous system, and thus increases in anxious patients regardless of their clinical diagnosis. On the other hand, development of new antidepressants and advances in receptor techniques, together with modern electrophysiologic and behavioural studies have given increasing support to a receptor supersensitivity hypothesis of depression, based on the evidence that antidepressants lead to subsensitivity or down regulation of beta-adrenoceptors, and adaptive changes may occur also in other receptor systems after two three weeks of antidepressant treatment. There is also growing evidence on the manifold interplay of noradrenergic and serotonergic systems in the mechanism of actions of effective antidepressant treatments, including the new and more selective therapeutic compounds. The rapidly increasing knowledge of the neurotransmitter receptors as well as of the relations between the different regulatory systems may lead to more specific intervention strategies in efforts to correct the biological malfunction in the heterogeneous collection of diseases classified as affective disorders. PMID- 2888935 TI - Effect of alpha-adrenoceptor stimulation of isolated canine, ferret and guinea pig airways. AB - Functional responses and subtypes of alpha-adrenoceptors in canine trachealis smooth muscle were investigated using the agonists; epinephrine, norepinephrine, SK&F 89748 (alpha 1-selective) and BHT-933 (alpha 2-selective) in the presence of a beta-adrenoceptor antagonist. Tissue contractility to these agonists was in the range of 16 to 46% of the maximum response to serotonin. SK&F 89748 was most effective in canine airways; however, the contractions could be abolished by methysergide. Neither precontraction of the airways by KCl nor degree of beta adrenoceptor blockade increased the reactivity of SK&F 89748 in this tissue. Reactivity of ferret and guinea pig airways to norepinephrine in the presence of beta-adrenoceptor blockade was insignificant. Responses of guinea pig airways to tyramine was about 1,000-fold less than those observed for vascular smooth muscle. Taken together these data suggest that alpha-adrenoceptors do not have any significance in the pathogenesis of airway hyperreactivity in dog, ferret and guinea pig airways. Moreover, adrenoceptors in guinea pig airways appear to be hormonal beta-adrenoceptors. PMID- 2888936 TI - Ritanserin assessments in plasma and CSF by means of HPLC technique with fluorescence detection. AB - A specific HPLC-technique based on fluorescence detection was developed for assay of ritanserin, a serotonin receptor-blocking agent, in plasma and CSF. In 5 ml sample volumes, the limit of detection was 0.5 ng/ml, the recovery of ritanserin was 83 +/- 5%, and the inter-assay variability, expressed as the coefficient of variation, was 9.5% in the 2-788 ng/ml concentration range. When the values determined by this technique were compared with the results obtained by means of an independent HPLC-method with UV-detection, the coefficient of correlation was 0.995 (p less than 0.001). However, our technique proved to be more specific and less complicated. PMID- 2888938 TI - [HTLV infections in women--a review]. PMID- 2888937 TI - Topographic brain mapping of EEG in neuropsychopharmacology--Part II. Clinical applications (pharmaco EEG imaging). AB - Multi-lead analysis of drug-induced changes in human brain function as monitored by the scalp-recorded electroencephalogram (EEG) and subsequent imaging of topographic pharmaco-EEG maps has become possible and practical with the advent of modern mini- and micro-computers. The present paper gives a survey about topographic analyses of pharmaco-EEG data obtained in systematic double-blind, placebo-controlled studies in normal healthy volunteers involving representative drugs of 5 different psychopharmacological classes, such as neuroleptics (chlorprothixene), antidepressants (imipramine), tranquilizers (diazepam), psychostimulants (caffeine), and antihypoxidotics/nootropics (pyritinol). The determination of cerebral bioavailability utilizing time- and dose-efficacy relations, as well as the evaluation of bioequipotency of different formulations of compounds is shown. Topographic pharmaco-EEG seems not only to confirm our previous knowledge that quantitative analysis of the human EEG in combination with certain statistical procedures ("quantitative pharmaco-EEG") is a valuable method to determine if, how, when and at which dosage a drug will be centrally effective, but also to have the potential to show effects of psychotropic drugs on the target organ--the human brain--which could not be previously picked up by single lead recordings. Topographic pharmaco-EEG imaging can be viewed as an enlargement of our armamentarium to better understand the mode of action of psychotropic drugs in human neuropsychopharmacology, as well as to monitor and (eventually) predict therapeutic efficacy in patients. PMID- 2888939 TI - Prediction of endocrine response in breast cancer by immunocytochemical detection of oestrogen receptor in fine-needle aspirates. AB - An immunocytochemical technique has been developed to detect the oestrogen receptor (ER) in samples obtained by fine-needle aspiration of primary or secondary breast carcinoma tissue. 45 (75%) of 60 samples contained sufficient cells for analysis. 19 (90%) of 21 patients who responded to endocrine therapy had samples with ER-positive cells compared with only 7 (39%) of 18 of those who did not respond (p less than 0.001). This test, which causes little pain to the patient and does not need a surgical biopsy, is as accurate as any other method of predicting the response to endocrine treatment in breast cancer. PMID- 2888940 TI - Human papillomavirus infections in women with and without abnormal cervical cytology. AB - 9295 smears, obtained from women attending three gynaecological hospitals for routine screening, were examined for human papillomavirus (HPV) types 6 and 11 and HPV 16 and 18 infections by filter in-situ hybridisation. The data were compared with cytological findings. In women with normal cytological smears HPV infection was identified in about 10% of women aged between 15 and 50 years and in less than 5% of those aged over 50. In women with abnormal smears (cervical intraepithelial neoplasia [CIN] I, II, and III and invasive cancer) HPV infection was detected in 35-40%; this rate seemed to be age-independent. the Peak incidence of CIN appeared several years after that of HPV infection. In women aged greater than 30 years it also declined earlier than did HPV positivity. The age-group distribution of women with CIN I, II, and III differed significantly from that of patients with invasive cancer. Only about a third of HPV-positive patients remained virus-positive, probably because of fluctuations in virus production and the insensitivity of the test system used. It is possible that filter in-situ hybridisation underestimates the total rate of HPV infections by a factor of 2 to 3. PMID- 2888941 TI - DNA polymorphism of human porphobilinogen deaminase gene in acute intermittent porphyria. AB - A common two-allele MspI restriction fragment length polymorphism of the human erythroid porphobilinogen (PBG)-deaminase gene was investigated in 33 unrelated patients with acute intermittent porphyria (AIP) and 20 controls. The polymorphism was tightly linked (lod score 3.14; no recombinants) to the locus for AIP as identified by measurement of erythrocyte PBG-deaminase activity. The frequency of the polymorphism in the AIP patients did not differ significantly from that in the controls. No common polymorphisms for eight other restriction endonucleases were found in either group. In 30 of the AIP patients no crossreacting immunological material (CRIM) was produced by the mutant PBG deaminase allele. The MspI polymorphism enabled each PBG-deaminase allele to be distinguished in subjects heterozygous for the polymorphism; thus a major gene deletion was excluded as the cause of the CRIM-negative mutation in all of the 18 families that contained an affected CRIM-negative individual heterozygous for the polymorphism. In suitable families, the MspI polymorphism provides a more certain way of identifying carriers of the AIP gene than current enzymatic methods and major gene deletions are unlikely to be present in more than a small proportion of the commonest type of AIP, the CRIM-negative form. PMID- 2888942 TI - Double-blind comparison of captopril alone against frusemide plus amiloride in mild heart failure. AB - Captopril alone as therapy for mild heart failure was compared with a combination of frusemide and amiloride in a double-blind randomised crossover trial in 14 patients who had previously been treated with diuretics. Although 10 patients remained stable on captopril alone, 4 patients deteriorated, with the development of pulmonary oedema of breathlessness. All 4 patients had had pulmonary oedema previously, unlike the patients who remained stable. Angiotensin converting enzyme inhibition alone is not sufficient treatment for patients with mild heart failure and a history of overt pulmonary oedema. PMID- 2888944 TI - Treatment for myelodysplastic syndromes. PMID- 2888943 TI - Blood and protein loss via small-intestinal inflammation induced by non-steroidal anti-inflammatory drugs. AB - Nearly three-quarters of patients on long-term treatment with non-steroidal anti inflammatory drugs (NSAIDs) have small-intestinal inflammation, the consequences of which are largely unknown. Two potentially important complications, blood and protein loss from the small intestine, have been studied. 49 patients on NSAIDs underwent study with an indium-111 labelled leucocyte technique which localises and measures intestinal inflammation. 32 patients underwent simultaneous study with technetium-99m labelled red blood cells (RBC), which showed identical sites of localisation to 111In-leucocytes in 19. Intestinal blood loss was measured in 8 patients by use of chromium-51 labelled RBC, and a significant correlation between blood loss and intestinal inflammation was found. Intestinal protein loss was assessed in 9 patients with 51Cr-labelled proteins; patients with NSAID induced small-intestinal inflammation were found to have a protein-losing enteropathy. These studies show that small intestinal inflammation caused by NSAIDs is associated with blood and protein loss, both of which may contribute to the general ill-health of rheumatic patients. PMID- 2888945 TI - Monitoring during general anaesthesia. PMID- 2888946 TI - Fish oils in rheumatoid arthritis. PMID- 2888947 TI - ICRF-187 and razoxane in cancer treatment. PMID- 2888948 TI - Myelopathy hand. PMID- 2888949 TI - Like PTH. PMID- 2888950 TI - Explanation for potency of repeated oral doses of morphine? AB - Morphine given by injection is the standard by which all other strong analgesics are measured, but when given orally in single doses it is a poor analgesic. With repeated oral administration it becomes very effective and it may be that on repeated dosage active metabolites, particularly morphine-6-glucuronide, account for much of the analgesic activity. Enterohepatic circulation may also contribute to the maintenance of blood and tissue levels of morphine and its metabolites in chronic use. PMID- 2888951 TI - Arm circumference and other factors in children at high risk of death in rural Bangladesh. AB - Mid upper arm circumference (MUAC) was measured monthly for 6 months in about 500 children aged 6-36 months from rural Bangladesh. Children who would die within 1 month of screening could be identified with 94% specificity and 56% sensitivity- almost twice the sensitivity achieved by other anthropometric screening schemes for this level of specificity. Specificity was slightly improved when the absence of breast-feeding, concurrent diarrhoea, oedema, and acute respiratory infection were taken into account. Children at high risk of death can be detected by monthly measurement of MUAC, which may be used in poor communities where interventions have to be selective. PMID- 2888952 TI - Experience with hepatitis B vaccination in nurses in a hospital for the mentally handicapped. AB - The extent of HBV infection in the staff of a large hospital for the mentally handicapped was investigated. Nurses with direct patient contact were identified as a particular risk group and hepatitis B vaccination was offered to them. Of the 500 who received a full course of vaccination 96% had detectable antibodies 9 months after starting vaccination. High titres (over 1000 IU/l) were found in 59.4%. Females responded better than males and the response was age-dependent. In only 2 of 20 non-responders did lasting immunity develop with a fourth dose of vaccine. Antibody titre decreased rapidly in all vaccinees followed up. In vaccinees with an initial titre above 100 IU/l the decrease in titre could be reversed by a booster dose. Those with a titre below 100 IU/l had a variable response to the booster dose and lasting immunity developed in only a few. A recall system was started that predicts when a booster dose will be required to maintain a protective level of antibody. Servicing such a vaccination programme is not easy. PMID- 2888953 TI - Are some hypertensive patients overtreated? A prospective study of ambulatory blood pressure recording. AB - Ambulatory blood pressure (BP) was recorded in hypertensive patients whose physicians had been asked to reduce diastolic pressure measured in the office to 90 mm Hg or less. 34 hypertensive patients with a diastolic pressure measured by their physician of 95 mm Hg or more despite antihypertensive therapy had their treatment changed with the aim of achieving this pre-set goal within 3 months. At the beginning and the end of the study, ambulatory BP was monitored during the daytime with a portable non-invasive recorder. The results of the ambulatory recordings were not made available to the physicians until completion of the study. In half the patients the ambulatory diastolic pressure was already 90 mm Hg or less at the start. In these patients, treatment adjustment did not further decrease ambulatory BP. In contrast, patients who initially had an ambulatory diastolic pressure above 90 mm Hg had a significantly decreased ambulatory BP at the end of the study. Intensifying the therapy of hypertensive patients who have a normal ambulatory BP may result in overtreatment without any real gain in BP control. PMID- 2888954 TI - Population screening for aortic aneurysms. PMID- 2888955 TI - Screening for abdominal aortic aneurysms. PMID- 2888956 TI - Cognitive function, undernutrition, and missed breakfast. PMID- 2888957 TI - Repetition strain injury. PMID- 2888958 TI - Cyclosporin, nifedipine, and gingival hyperplasia. PMID- 2888959 TI - Non-invasive diagnosis of cardiac sarcoidosis. PMID- 2888960 TI - Neonatal long lines for intravenous antibiotic therapy in cystic fibrosis. PMID- 2888961 TI - Propofol infusion and green urine. PMID- 2888962 TI - Neonatal afibrinogenaemia due to sodium valproate. PMID- 2888963 TI - Immunity in sarcoidosis. PMID- 2888964 TI - Intravenous immunoglobulin and blood group antibodies. PMID- 2888965 TI - Outbreak of psittacosis associated with a cockatiel. PMID- 2888966 TI - Diverse tropism of HBLV (human herpesvirus 6) PMID- 2888967 TI - Marin County agent, an astrovirus. PMID- 2888968 TI - Immune basis for pre-eclampsia evidence from oocyte recipients. PMID- 2888969 TI - Leucoerythroblastosis in breast carcinoma. PMID- 2888970 TI - Clinical relevance of a serological cross-reaction between Escherichia coli O157 and Brucella abortus. PMID- 2888971 TI - Academic medical staff changes in England and Wales 1984-87. PMID- 2888972 TI - Mortality and social class. PMID- 2888973 TI - Self experimentation. PMID- 2888974 TI - Adjuvant tamoxifen in breast cancer. PMID- 2888975 TI - Father Damien, leper priest. PMID- 2888976 TI - Tobacco-sponsored sport on television. PMID- 2888977 TI - Awareness of hypoglycaemia in diabetes. PMID- 2888978 TI - Insulin and hypertension. PMID- 2888979 TI - Tannin and oesophageal cancer. PMID- 2888980 TI - Treatment of menorrhagia. PMID- 2888981 TI - Serum creatine kinase (brain specific) as predictor for impaired psychomotor development of very preterm infants. PMID- 2888982 TI - Should AIDS be notifiable? PMID- 2888983 TI - Aggressive psychosis in AIDS patient on high-dose steroids. PMID- 2888984 TI - Peptide T[4-8] is core HIV envelope sequence required for CD4 receptor attachment. PMID- 2888985 TI - Brazilian purpuric fever: epidemic purpura fulminans associated with antecedent purulent conjunctivitis. Brazilian Purpuric Fever Study Group. AB - In late 1984, 10 children in a small, rural town in Brazil had high fever associated with vomiting and abdominal pain. Within 12-48 h of the onset of fever, purpura developed associated with vascular collapse and peripheral necrosis. All 10 children died. Cerebrospinal fluid examinations did not suggest meningitis and, when done, tests were negative for Neisseria meningitidis. Other culture, serological, and necropsy examinations did not reveal a cause. Case finding uncovered another cluster of similar illness in children in a second town and sporadic cases in five other cities. Two case-control studies demonstrated that children who became ill were significantly more likely than control children to have had conjunctivitis during the month before illness. This conjunctivitis was purulent, preceded the onset of more severe disease by 3-15 days, and had resolved before fever began. Although no conjunctival cultures were obtained from case-children, Haemophilus aegyptius was the most common pathogen isolated from other conjunctival cultures during the epidemic. This organism was also isolated from a non-aseptic skin scraping from 1 case child. A 25-megadalton plasmid distinguished the H aegyptius isolates epidemiologically associated with illness from other Brazilian conjunctival isolates. Brazilian purpuric fever is a newly recognized syndrome of epidemic purpura fulminans associated with antecedent purulent conjunctivitis, possibly caused by H aegyptius. PMID- 2888986 TI - Haemophilus aegyptius bacteraemia in Brazilian purpuric fever. Brazilian Purpuric Fever Study Group. AB - Brazilian purpuric fever (BPF) is a fulminant, often fatal childhood illness that was first recognised in 1984. An outbreak in Serrana, Sao Paulo State in March to May, 1986, resulted in 11 cases. Haemophilus aegyptius was isolated from normally sterile body fluids in 10 children (9 from blood and 1 from cerebrospinal fluid contaminated with blood), consistent with a direct role for H aegyptius in the pathogenesis of BPF. The ability to define cases by positive blood cultures permitted an evaluation of the spectrum of illness of this disease. 5 culture positive cases were clinically similar to those previously described; the other 5 had milder illness without petechial or purpuric skin manifestations at the time the bacterium was isolated. Blood cultures were a sensitive means of diagnosing BPF; cultures were positive in 5 of 6 patients that met the full clinical case definition. Treatment of conjunctivitis did not appear to prevent BPF. However, children treated with intravenous antimicrobials early in the systemic illness had a trend toward better survival, suggesting that early therapy may prevent progression of the illness. PMID- 2888987 TI - Acute and chronic pituitary failure resembling Sheehan's syndrome following bites by Russell's viper in Burma. AB - Pituitary function was investigated in 9 patients in shock after Russell's viper bites and in 24 individuals who had been severely envenomed 2 weeks to 24 years previously. 3 out of 9 patients had hypoglycaemia and inappropriately low serum cortisol, plasma growth hormone, and plasma prolactin concentrations. 4 who died had pituitary haemorrhage and 1 had adrenal haemorrhage as well. Of the 24 who had apparently recovered from bites, 7 had clinical features of hypopituitarism and no response in plasma growth hormone or prolactin concentrations to symptom producing insulin-induced hypoglycaemia. 4 of these 7 had a sluggish serum cortisol response to 'Synacthen Depot' and 5 had an abnormal cortisol response to hypoglycaemia. 4 men with symptoms who were tested had low serum testosterone concentrations; serum thyroxine was also low in these men but not in 2 women with menstrual disturbances and impaired insulin responses. Of the 17 individuals without clinical evidence of endocrine disease, 4 had pituitary hormonal abnormalities. Russell's viper envenoming may thus produce a disorder resembling Sheehan's syndrome. PMID- 2888988 TI - Cell-mediated cytotoxic response to respiratory syncytial virus in infants with bronchiolitis. AB - A cell-mediated cytotoxic response to respiratory syncytial (RSV) was demonstrated in the peripheral blood of 4 of 22 infants with acute bronchiolitis. These 4 infants were aged 3 weeks to 3 months. No such response was found in infants older than 4 months. All 4 infants with a positive response had mild infections. PMID- 2888989 TI - Autonomic function in mitral valve prolapse. PMID- 2888990 TI - Obstructive sleep apnoea and lower airways obstruction. PMID- 2888991 TI - Schizophrenia and organic disease. PMID- 2888992 TI - Conservative management of the ruptured spleen. PMID- 2888993 TI - Difficult intubation. PMID- 2888994 TI - Dyspepsia: a dilemma for doctors? PMID- 2888995 TI - Clinic experience of prenatal diagnosis of cystic fibrosis by use of linked DNA probes. AB - 96 families at risk of having a child with cystic fibrosis have been counselled about prenatal diagnosis by the use of linked DNA probes. Of the first 30 pregnancies 9 children have been born and confirmed to be free from CF, as predicted; 8 pregnancies were terminated (1 of these was found to be miscarrying at time of termination); 12 pregnancies, in which the fetuses are predicted to be unaffected, are in progress; and 1 has miscarried. No couple with a prenatal prediction of CF decided to continue with the pregnancy. 1 pregnancy was terminated because of a 50:50 chance of an affected fetus. In 1 twin pregnancy the affected fetus was selectively aborted, and the other baby was confirmed after birth to be unaffected, as predicted. In the other twin pregnancy the two chorionic plates could not be samples separately; the pregnancy was continued on the basis of normal findings for the lower plate, and both twins have turned out to be normal. Many couples at risk see early prenatal diagnosis as a way to help them have an unaffected child. PMID- 2888997 TI - Decisions to limit treatment. PMID- 2888996 TI - Are children with lymphoblastic leukaemia given enough 6-mercaptopurine? PMID- 2888998 TI - The Pasteur Institute. PMID- 2888999 TI - Treatment of myotonia. PMID- 2889000 TI - Double-contrast barium enema. PMID- 2889001 TI - Breath alcohol analysis. PMID- 2889002 TI - Endoscopic ultrasound: radiologist or endoscopist, not both. PMID- 2889003 TI - Pre-eclampsia and trisomy 13. PMID- 2889004 TI - N-myc oncogene amplification and catecholamine metabolism in patients with neuroblastoma. PMID- 2889005 TI - Repeated low doses of anti-rhesus gammaglobulin in aplastic anaemia. PMID- 2889006 TI - Topical podophyllin for genital warts. PMID- 2889007 TI - Immunosuppressant therapy in AIDS. PMID- 2889008 TI - Zidovudine for lymphocytic interstitial pneumonia associated with AIDS. PMID- 2889009 TI - Particle agglutination assay for anti-HIV. PMID- 2889010 TI - Borrelia infection as a cause of presenile dementia. PMID- 2889011 TI - Non-parenterally transmitted non-A, non-B hepatitis in children in the UK. PMID- 2889012 TI - Survival and calcaemic status of geriatric inpatients. PMID- 2889013 TI - Calcium carbonate as phosphate binder in dialysis. PMID- 2889014 TI - Neuroendocrine differentiation in atrial myxomas. PMID- 2889015 TI - Post-herpetic neuralgia. PMID- 2889016 TI - Hallucinations during morphine administration. PMID- 2889018 TI - Psychopathology of violence. PMID- 2889017 TI - Retinoids and malignancy. PMID- 2889019 TI - Unilateral Raynaud's symptoms evoked during dream report. PMID- 2889020 TI - Temazepam abuse. PMID- 2889021 TI - Adolescent colorectal cancer and dioxin exposure. PMID- 2889022 TI - Early diagnosis of malignant melanoma by surface microscopy. PMID- 2889023 TI - Lysosomal alpha-N-acetylgalactosaminidase deficiency: a new inherited metabolic disease. PMID- 2889024 TI - Linkage of tuberous sclerosis to ABO blood group. PMID- 2889025 TI - Susceptibility to coeliac disease involves genes in HLA-DP region. PMID- 2889026 TI - Low prevalence of Huntington's disease in Finland. PMID- 2889027 TI - Genetic typing and confirmation of parenthood. PMID- 2889028 TI - Anomalous protein complement of sperm nuclei in some infertile men. PMID- 2889029 TI - Difficulties for the European Regional Committee. PMID- 2889030 TI - Cancer in offspring of long-term survivors of childhood and adolescent cancer. AB - A multicentre retrospective cohort study of long-term survivors of childhood and adolescent cancer identified 7 cases of cancer among 2308 offspring (0.30%) of 2283 case-survivors and 11 cases among 4719 offspring (0.23%) of 3604 controls. Overall, the observed numbers of cases were not significantly different from those expected in the general population. Among offspring of case-survivors observed for the first 5 years of life, the group with the most person-years of follow-up, 5 cancers were reported (3 confirmed), compared with 1.7 expected, a significant excess due mostly to boys whose mothers survived cancer. Some offspring with cancer had known single-gene traits; others resembled previously recognised patterns of family cancer. The remainder may represent chance occurrences or new cancer family syndromes, such as an association with malignant melanoma. The study had an overall 79% power to detect a 3-fold excess of cancer among offspring of case-survivors, but no excess was observed. The number person years of follow-up in the second decade of life, when most cases of cancer developed, was small. PMID- 2889031 TI - Erythrocyte crenation induced by free fatty acids in patients undergoing extracorporeal circulation. AB - Normal erythrocyte morphology is necessary for proper distribution of blood-flow in the microcirculation. Erythrocyte shape was studied in 20 patients undergoing extracorporeal circulation (EC) during coronary bypass surgery. Crenated erythrocytes comprised a mean 64% of all erythrocytes during and 29% after EC. Free fatty acid (FFA) content of the erythrocyte membranes was significantly increased at both times, and FFA content correlated with the proportion of crenated erythrocytes. Washing crenated cells with defatted albumin solution transformed them back to discocytes, simultaneously removing more FFA than that removed from pre-EC discocytes. The plasma FFA to albumin ratio became disproportionately increased during EC; the increased level correlated with severity of erythrocyte crenation. Maintaining a higher level of albumin during EC by adding 50 g human albumin to the extracorporeal system prevented erythrocyte crenation. Entry of plasma FFA not bound to albumin into erythrocyte membranes during EC causes massive erythrocyte crenation. PMID- 2889032 TI - Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age. AB - The sodium retention associated with liquorice ingestion has been thought to be due to a direct mineralocorticoid effect, despite the fact that it does not seem to occur in patients or animals with severe adrenal insufficiency. This study in seven normal subjects given liquorice showed that sodium retention is associated with a significant change in cortisol metabolism indicating inhibition of 11-beta hydroxysteroid dehydrogenase (11 beta-OHSD). Congenital deficiency of this enzyme produces a syndrome of apparent mineralocorticoid excess. It is suggested that in both conditions there is a defect in the renal conversion of cortisol to cortisone by 11 beta-OHSD which results in high intrarenal cortisol levels, acting on type 1 mineralocorticoid receptors to cause sodium retention. PMID- 2889033 TI - Influence of major histocompatibility complex region genes on human longevity among Okinawan-Japanese centenarians and nonagenarians. AB - The frequencies of 80 HLA antigen phenotypes in 82 centenarians and 20 nonagenarians in Okinawa, Japan, were compared with those in other healthy adults in various age-brackets. Subjects aged over 90 had an extremely low frequency of HLA-DRw9 and an increased frequency of DR1. In this age-group the relative risk of corrected (for number of antigens) p value for HLA-DRw9 were 5.2 and 0.0001, respectively; those for HLA-DR1 were 13.3 and 0.0367, respectively. Since a high frequency of DRw9 and a low frequency of DR1 are associated with autoimmune or immune deficiency diseases, the genetic protection against these disorders may contribute to longevity. PMID- 2889034 TI - Sexual abuse of children. PMID- 2889035 TI - Proteases, antiproteases, and emphysema. PMID- 2889036 TI - Osteoporosis. PMID- 2889037 TI - Tropical ulcers. PMID- 2889038 TI - Made to last. PMID- 2889039 TI - Facial cooling and perception of dyspnoea. PMID- 2889040 TI - Child sexual abuse--an increasing rate of diagnosis. AB - In 2 years in Leeds, two paediatricians diagnosed sexual abuse in 94 boys and 243 girls. 38% were under 5 at diagnosis and the mean age was 8.0 years. 39% presented following disclosure by the child. 83% of boys and 25% of girls had anal signs and 58% of girls had genital signs. 60% of abusers were related to the child and half of these were natural fathers. 25% of all abusers were teenagers and 5% were women. The abuser was convicted in 25% of cases and protective legal orders were sought in 36%. Sexual abuse is emerging as a major child and mental health problem that requires new resources in training and personnel. PMID- 2889041 TI - Investigation of the sexually abused child. PMID- 2889042 TI - New dosimetry of atomic bomb radiations. AB - The reassessment of the radiation dosimetry from the Hiroshima and Nagasaki atomic bombs is almost complete. Since atomic bomb survivors provide a major source of data for estimates of risk of cancer induction by radiation the impact of the new dosimetry on risk estimates and radiation protection standards is important. The changes include an increase of about 20% in the estimated yield of the Hiroshima bomb and a reduction in the estimated doses from neutrons in both cities. The estimated neutron dose for Hiroshima is about 10% of the previous estimate. The neutron doses are now so small that direct estimates of neutron relative biological effectiveness may be precluded or be much more difficult. There is little change in most of the gamma ray organ doses because various changes in the new estimates tend to cancel each other out. The new estimate of the attenuation of the free-in-air kerma by the walls of the homes is about twice that used in the previous dosimetry. But the transmission of gamma radiation to the deep organs such as bone marrow is significantly greater than earlier estimates. Probably future risk estimates for radiogenic cancer will be somewhat higher because of both the new dosimetry and the new cancer mortality data. New risk estimates should be available in 1988. PMID- 2889043 TI - Antibodies to neutrophil cytoplasmic antigen in systemic vasculitis. PMID- 2889044 TI - New treatment for infertility due to congenital absence of vas deferens. PMID- 2889045 TI - Barrett's oesophagus. PMID- 2889046 TI - Nebulised budesonide in severe infantile asthma. PMID- 2889047 TI - Low frequency of slow debrisoquine hydroxylation in a native Chinese population. PMID- 2889048 TI - Chemotherapy free survival. PMID- 2889049 TI - Myelosuppression after methotrexate, mitozantrone, and mitomycin C combination chemotherapy. PMID- 2889050 TI - Hypertrophic cardiomyopathy associated with hereditary spherocytosis in three generations of one family. PMID- 2889051 TI - Bone erosions in rheumatic diseases. PMID- 2889052 TI - Plasmid-mediated resistance to nalidixic acid and new 4-quinolones? PMID- 2889053 TI - Chlamydia trachomatis in antenatal clinics. PMID- 2889054 TI - Transabdominal placental biopsy. PMID- 2889055 TI - Oestradiol implants: what dose, how often? PMID- 2889056 TI - Changing pattern of duodenal ulcer? PMID- 2889057 TI - Dihydroergotamine and the pelvic pain syndrome. PMID- 2889058 TI - Modified trimethoprim-sulphamethoxazole doses in Pneumocystis carinii pneumonia. PMID- 2889059 TI - Delayed appearance of HIV infection in children. PMID- 2889060 TI - Modification of HIV competitive assay to reduce frequency of false negative results. PMID- 2889061 TI - Life-threatening hyperkalaemia after bladder decompression for high pressure chronic retention. PMID- 2889062 TI - Exchanging kidney transplants. PMID- 2889063 TI - Rank injustice and academic promotion. PMID- 2889064 TI - Cervical cancer screening. PMID- 2889065 TI - AIDS advice to haemophiliacs. PMID- 2889066 TI - Prognosis of meningococcal septicaemia. PMID- 2889067 TI - Epidemic group A meningococcal disease in Haj pilgrims. PMID- 2889068 TI - Cardiac arrhythmias caused by nebulised beta-agonist therapy. PMID- 2889069 TI - DNA typing of genital warts and diagnosis of sexual abuse in children. PMID- 2889070 TI - Microhaematuria in children: starting point for adult hypertension? PMID- 2889071 TI - Reye's syndrome and aspirin. PMID- 2889072 TI - Small round structured viruses and persistence of infectivity in food handlers. PMID- 2889073 TI - Viral gastroenteritis and food handlers--melon off the menu. PMID- 2889074 TI - Amiodarone and thyroid. PMID- 2889075 TI - Anatomical variation and percutaneous liver biopsy failure. PMID- 2889076 TI - Loss of life from heart attacks at different ages. PMID- 2889077 TI - Metallothionein and copper in liver disease. PMID- 2889078 TI - Advising pregnant women in Ireland to go abroad for abortion is unlawful. PMID- 2889079 TI - Long-term effects of intravenous thrombolysis in acute myocardial infarction: final report of the GISSI study. Gruppo Italiano per lo Studio della Streptochi nasi nell'Infarto Miocardico (GISSI). AB - Long-term follow-up of 98.3% of the 11,712 patients recruited in the GISSI trial of intravenous streptokinase (SK) in acute myocardial infarction has shown persistence of the beneficial effect observed during the hospital phase. At 12 months a significant difference in mortality was seen in the whole population (17.2% in SK group versus 19.0% in controls, p = 0.008, relative risk 0.90), and in the 0-3 and 3-6 h groups (relative risks 0.89 and 0.87, respectively). For most of the other strata according to which the trial population has been analysed, the magnitude and the direction of the effects were also substantially the same as those recorded in the hospital phase. SK thrombolysis should be considered among the recommended treatments of the acute phase, at least up to 6 h from onset of myocardial infarction. PMID- 2889080 TI - Aortic and mitral valve calcification in patients with end-stage renal disease. AB - The frequency and aetiology of aortic valve and mitral annular calcification was studied by echocardiography in 87 patients aged 35-70 on maintenance haemodialysis for a mean of 7.5 years (range 0.5-19). Aortic valve calcification (AVC) was found in 24 patients (28%) and mitral annular calcification (MAC) was found in 31 (36%). AVC was severe and produced aortic stenosis in 5 patients with a tricuspid aortic valve (mean age 51.6 years), which confirms that calcific aortic stenosis is a complication of chronic uraemia. MAC was associated with functional mitral stenosis in 1 patient. Premature AVC and MAC were associated with an increased calcium X phosphate product and long-term haemodialysis. There were no significant differences between those patients with aortic stenosis and those with AVC but no stenosis. Patients with AVC had an increased incidence of MAC and vascular calcification. Premature AVC and MAC is frequent in dialysis patients and appears to be related to abnormal calcium and phosphate metabolism and to increased mechanical stress on the valve cusps. In a small but important group of patients on long-term dialysis, premature valve calcification is severe and produces aortic stenosis, or less frequently, mitral stenosis. PMID- 2889081 TI - Placebo-controlled trial of recombinant alpha 2-interferon in Chinese HBsAg carrier children. AB - 24 Chinese children aged 1.5-5 years and positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B virus DNA polymerase (HBV DNAp), and HBV DNA on at least three occasions in the 6 months before the trial were randomised to receive either vitamin B complex or intramuscular recombinant alpha 2-interferon (r-IFN) ('Roferon') 10 X 10(6) IU/m2 thrice weekly for 12 weeks. In all 12 subjects receiving r-IFN, HBV DNAp and HBV DNA levels fell during the course of r-IFN injections. Within 4 weeks of cessation of r-IFN injection, the HBV DNAp and HBV DNA returned to pre-trial levels except in 2 subjects, in whom loss of HBV DNAp and HBV DNA was sustained for up to 18 months from onset of the trial. 1 child lost HBeAg at 18 months. 2 of the 12 children in the placebo group also had a sustained loss of HBV DNAp and HBV DNA during the 18 months, with 1 child losing HBeAg at 18 months. All 24 subjects remained positive for HBsAg. r-IFN produced very slight side-effects except for pyrexia and the "flu" syndrome, both of which showed rapid tachyphylaxis. In the dose given r-IFN was safe but had no long-term beneficial effects on HBsAg carriage in Chinese children. PMID- 2889082 TI - Selective immunodeficiency affecting staphylococcal response. AB - Eight patients with recurrent staphylococcal infections, necessitating up to 213 hospital admissions in one patient, gave normal results with the usual immunological investigations, including measurement of serum IgG and IgG2. In the staphylococcal inhibition test all showed persistently subnormal results, corrected by the addition of compatible normal plasma or normal IgG therapy for 6 months to 21 years, and one died from staphylococcal septicaemia 6 months after withdrawal of treatment. The impairment in anti-staphylococcal response, with failure to produce adequate antibodies, was probably acquired in utero in four patients and inherited in two. In these six patients symptoms started soon after 4 months. In the remaining two the syndrome was acquired later in life. PMID- 2889083 TI - Atrial natriuretic peptide and blood pressure in a geographically defined population. AB - Plasma atrial natriuretic peptide (ANP) was measured in 717 subjects in a cross sectional study of patients with hypertension (treated and untreated) and normotensive controls, representatives of a geographically defined population. ANP concentrations did not differ between the groups and there was no correlation with blood pressure. These results do not support the view that hypertensive and normotensive subjects have different ANP concentrations; they also call into question the role of ANP in the development of high blood pressure. PMID- 2889085 TI - A continuum of psychosis? PMID- 2889084 TI - The carotid siphon: a natural arterial filter? PMID- 2889086 TI - The International Water Decade. PMID- 2889087 TI - Duodenal ulcers in childhood. PMID- 2889088 TI - Drop-outs from clinical trials. PMID- 2889089 TI - What eye test tests eyes best? PMID- 2889090 TI - Paediatric intensive care units. PMID- 2889091 TI - Energy requirements of pregnancy. An integrated study in five countries: background and methods. PMID- 2889092 TI - Energy requirements of pregnancy in Scotland. AB - Measurements of energy intake, basal metabolic rate, body weight and composition, and physical activity were made on 88 women throughout pregnancy. Mean weight gain (from 10 wk to 40 wk gestation) was 11.7 kg, birthweight 3370 g, and placental weight 641 g. Maternal fat gain (from 10 wk) calculated by three methods was 2.1 kg. The total rise in basal metabolism for the whole of pregnancy was calculated to be 126 MJ (1 MJ = 239 kcal). The total increase in energy intake was estimated as 88 MJ. There was little evidence of any changes in either the energy cost of physical activity or the time spent in these activities. The total energy cost of laying down fetal and maternal tissues and the increased metabolism was 281 MJ, which was offset by a possible increase in energy intake of only 88 MJ. The most likely explanation for the deficit of 193 MJ is that many small reductions in energy expenditure occurred which were not detectable by the methods used. PMID- 2889093 TI - Salmonella ealing infections associated with consumption of infant dried milk. AB - In an outbreak of Salmonella ealing infections in November and December, 1985, the proportion of infants infected was in excess of the normal distribution pattern and the cases were geographically widespread. All the infected infants had been fed with a dried-milk product from one manufacturer. Despite intensive efforts to isolate S ealing from packets of the product, it was found only in low numbers in 4 of 267 sealed packets. The source of infection was traced to the factory spray-drier, which had a hole in its inner lining, allowing escape of powder and its return from contaminated insulation material. The plant was closed and the equipment scrapped and later replaced. It is recommended that raw milk and whey, which frequently contain salmonellae, should not be allowed onto the site of milk-drying plants. PMID- 2889094 TI - Quinolone/ureidopenicillin cross-resistance. PMID- 2889095 TI - Treatment of loin pain/haematuria syndrome by renal autotransplantation. PMID- 2889096 TI - Guidelines on halothane hepatitis. PMID- 2889098 TI - Missed psychiatric cues. PMID- 2889097 TI - Apnoeic oxygenation of a brain-dead patient. PMID- 2889099 TI - Familial retinol-binding-protein deficiency? PMID- 2889100 TI - Increasing incidence of cancer of the tongue in the United States among young adults. PMID- 2889101 TI - Fate of conceptuses after IVF. PMID- 2889102 TI - Rising mortality from cancer of the tongue in young Scottish males. PMID- 2889103 TI - Vacuolated erythrocytes. PMID- 2889104 TI - Hepatitis B vaccine and health workers' compensation claims. PMID- 2889105 TI - Nicaragua: war and mental health. PMID- 2889106 TI - Chile's academics under threat. PMID- 2889107 TI - Autonomic neuropathy and HIV infection. PMID- 2889108 TI - Conditions in Brixton Prison hospital block. PMID- 2889109 TI - Tobacco-sponsored sport on television. PMID- 2889110 TI - Isolation of HIV-1 from monocytes but not T lymphocytes. PMID- 2889111 TI - Routine tests for HIV antigen. PMID- 2889112 TI - Value of screening for sexually transmitted diseases in patients requesting HIV testing. PMID- 2889113 TI - Campylobacter pylori and gastric manipulation for morbid obesity. PMID- 2889114 TI - Renal hypophosphataemia has several mendelian forms. PMID- 2889115 TI - Pathophysiology of myalgic encephalitis. PMID- 2889116 TI - "Peroxidation" in the central nervous system. PMID- 2889117 TI - Awareness of hypoglycaemia in diabetes. PMID- 2889118 TI - Vitamin B12 deficiency, demyelination, and multiple sclerosis. PMID- 2889119 TI - Itraconazole and cyclosporin nephrotoxicity. PMID- 2889120 TI - Serum levels of interleukin-6 and acute phase responses. PMID- 2889121 TI - Scope and limitations of in vivo brain dialysis: a comparison of its application to various neurotransmitter systems. AB - Brain dialysis is rapidly becoming a routine research method with a wide range of applications. Since 1982 this sampling technique is frequently used as a method to study the in vivo release of endogenous neurotransmitters such as dopamine, noradrenaline, serotonin, acetylcholine and certain amino acids. In this review most of the studies that have appeared in this field, are evaluated. Special attention was given to the question whether the neurotransmitter content in the dialysate is related to neurotransmission. Criteria such as the presence of a high tissue/dialysate concentration ratio, the sensitivity of the transmitters to membrane active compounds and the occurrence of receptor-mediated effects, are discussed. It is concluded that dopamine, noradrenaline and acetylcholine found in the dialysate are directly derived from neurotransmission, whereas the overflow of excitatory amino acid neurotransmitters is related to neurogenic as well as to metabolic events. PMID- 2889122 TI - Effects of naloxone on basal and vagus nerve-induced secretions of GRP, gastrin, and somatostatin from the isolated perfused rat stomach. AB - The effects of naloxone, an opiate antagonist, on basal and vagus nerve-induced secretions of GRP, gastrin, and somatostatin were examined using the isolated perfused rat stomach prepared with vagal innervation. Naloxone (10(-6) M) significantly inhibited basal somatostatin secretion in the presence and absence of atropine and of hexamethonium, whereas basal GRP and gastrin secretion was not affected by naloxone. Electrical stimulation (10 Hz, lms duration, 10V) of the distal end of the subdiaphragmatic vagal trunks elicited a significant increase in both GRP and gastrin but a decrease in somatostatin. Naloxone (10(-6) M) failed to affect these responses in the presence or absence of atropine. On the other hand, when hexamethonium was infused, naloxone significantly inhibited both the GRP and gastrin responses to electrical vagal stimulation. Somatostatin secretion was unchanged by vagal stimulation during the infusion of hexamethonium with or without naloxone. These findings suggest that basal somatostatin secretion is under the control of an opiate neuron and that opioid peptides might be involved in vagal regulation of GRP and gastrin secretion. PMID- 2889123 TI - Influence of experimental acute renal failure on somatostatin levels and binding in rabbit fundic and duodenal mucosa. AB - Rabbits with bilateral ureteral ligation of four-days duration showed a significant decrease of somatostatin content in gastric fundic mucosa (but not in proximal duodenal mucosa) as well as in the binding capacity of both high- and low-affinity binding sites without changes in the affinity values in cytosol of fundic and proximal duodenal mucosa, whereas the fasting plasma somatostatin levels increased as compared to control conditions. The number of somatostatin binding sites was inversely related to plasma levels of the peptide and support the hypothesis of somatostatin regulating its own binding sites. The current finding provides evidence that diminished somatostatin binding may be a contributory factor in the somatostatin gastroduodenal resistance of uremia. PMID- 2889124 TI - Antagonism of AP-5- and amphetamine-induced behaviour by timelotem as compared with clozapine and haloperidol. AB - Bilateral intrastriatal injection of DL-2-amino-5-phosphonovaleric acid (AP-5), that blocks glutamatergic transmission at the N-methyl-d-aspartate preferring receptor, induces sniffing and body turns and reduces grooming in rats. Timelotem, a representative of the newly developed chemical class of anellated benzodiazepines antagonized specifically AP-5-induced sniffing and body turns. Classical (haloperidol) as well as atypical (clozapine) neuroleptics had recently been shown to antagonize AP-5-induced sniffing; clozapine, like timelotem, but not haloperidol, additionally antagonized AP-5-induced body turns. Further, timelotem antagonized amphetamine-induced stereotyped behaviour in rats, but was found less active than haloperidol in this test. Comparing the activity of drugs in both paradigms revealed that haloperidol inhibited AP-5-induced sniffing and amphetamine-induced stereotypies within the same dose range, but timelotem and clozapine were found more potent in the AP-5 test than in the amphetamine test. Thus, detailed drug profiles discriminate timelotem and clozapine from haloperidol, linking timelotem again to atypical antipsychotic compounds. PMID- 2889125 TI - Prednisone decreases CSF somatostatin in healthy humans: implications for neuropsychiatric illness. AB - Several neuropsychiatric illnesses, including depression and Alzheimer's disease, are reported to be characterized by hypercortisolemia and by reduced levels of cerebrospinal fluid somatostatin-like immunoreactivity (CSF-SLI). To investigate a possible causal linkage between these abnormalities we administered prednisone, 80 mg orally per day for 5 days, to 9 healthy volunteers. We observed significant prednisone-induced reductions in CSF-SLI. Moreover, the magnitude of these reductions was inversely related to the magnitude of prednisone-induced reductions in plasma ACTH levels, suggesting a functional interaction between circulating corticosteroids, central somatostatin and pituitary ACTH release. PMID- 2889126 TI - [Radiation pathomorphology of the APUD system]. AB - Complex histological, histochemical, immunological and electron-microscopic studies made it possible to receive new data on functional morphology of the endocrine cells of the APUD system in norm, radiation exposure and tumor growth. The data obtained are being discussed and analysed and optimal methods of optimization of radiation and chemotherapy of malignant tumors are being developed. PMID- 2889127 TI - [Treatment of arterial hypertension]. PMID- 2889128 TI - [50th anniversary of the death of the distinguished statesman G. K. Ordzhonikidze (1886-1937)]. PMID- 2889129 TI - Identification of regulatory elements of cloned genes with functional assays. PMID- 2889130 TI - Incidence and some characteristics of fimbriae FY and 31A of Escherichia coli isolates from calves with diarrhea in Japan. AB - Escherichia coli isolates from calves with diarrhea (1 day to 8 weeks old, 140 individuals) were surveyed for the three immunologically distinct fimbrial adhesins FY, 31A, and K99. Of a total of 1,370 strains isolated, 96 (7.0%), 34 (2.5%), 75 (5.5%), and 13 (0.9%) were identified as FY+, 31A+, FY+.31A+, and K99+, respectively. The K99+ strains also manifested heat-stable enterotoxin production (ST+), while FY+, 31A+, and FY+.31A+ strains were ST-. Expression of FY and 31A was repressed at lower temperatures or poor aeration. The FY+ and 31A+ E. coli showed mannose-resistant hemagglutinating activity with bovine erythrocytes. Electron microscopy revealed that FY is a gently curled fimbria with a mean diameter of 4.2 nm, and 31A is a fimbria with a mean diameter of 5.1 nm. The molecular mass of protein subunits was found to be approximately 20 kilodaltons (Kd) and 19 Kd for FY and 31A, respectively. Lethal diarrhea of neonatal calves was induced by challenge with the combination of a K99+.ST+ E. coli strain and either a 31A+ E. coli strain or a 31A+ E. coli strain plus an FY+ E. coli strain under the experimental conditions in which lethal diarrhea was not induced by challenge with a K99+.ST+ E. coli strain alone. PMID- 2889131 TI - The role of melatonin and serotonin in aging. AB - The hypothesis presented in this paper defines aging as a pathological process originating in the pineal gland. This results in a diminished output of melatonin, along with a diminished melatonin to serotonin ratio, leading to a decline in adaptive processes and a predictable syndrome manifested by the "diseases of the aged" (DOA) and subsequent death of the organism. That is, aging is a syndrome of relative melatonin deficiency resulting from the gradual failure of the pineal gland. PMID- 2889132 TI - Lipids covalently bonded to pteridines and to nucleotides may bind neurotransmitters, and may be cleaved into second messengers for opiates. AB - By hypothesis: 1.) lipid-pteridines and lipid-nucleotides, while fixed in the external side of membranes at the ends of nerve cells, bind neurotransmitters and perhaps opiates; 2.) during their normal metabolism in animals they are cleaved by phospholipases into pteridines and nucleotides which act as 2nd messengers for opiates. These 2nd messengers, some with tri-iodo-thyronine, act by sandwiching about circulating neurotransmitters; 3.) dinucleotides containing neopterin are specific 2nd messengers for steroids; and 4.) lipid-RNAs are the molecular locations in the brain which contain memories. PMID- 2889133 TI - Unnecessary investigations for impalpable testes. PMID- 2889134 TI - The treatment of psychiatric disorders in patients with chronic airways obstruction. AB - Patients with chronic airways obstruction have been reported as presenting with psychiatric illnesses commonly. The anxiety and depressive disorders, which are the most common psychiatric illnesses, are known significantly to affect patients' level of occupational and social function. Four cases are presented to illustrate the differing presentations of psychiatric illness in patients with chronic airways obstruction. Conventional psychiatric treatment modalities can be used successfully, in spite of severe airways obstruction, and may lead to a markedly improved quality of life for these patients. PMID- 2889135 TI - [Clinical observations in acute benzodiazepine poisoning]. PMID- 2889136 TI - [Urinary secretion of alpha-glucosidase, N-acetyl-glucosaminidase and alanine aminopeptidase in the healthy newborn infant at term]. PMID- 2889137 TI - Allogenotypes defined by short DQ alpha and DQ beta cDNA probes correlate with and define splits of HLA-DQ serological specificities. AB - HLA-DR and -DQ serotyped cell lines and peripheral blood leucocytes were analysed by Southern blot allogenotyping. Using a short DQ beta cDNA probe, a DQ beta allelic series was defined by restriction fragment length polymorphism (RFLP) with the restriction endonuclease TaqI. This DQ beta allelic series correlates with, and defines splits of, the HLA-DQ serological specificities DQw1 (DQ beta 1a and DQ beta 1b RFLPs), DQw2 (DQ beta 2a and DQ beta 2b RFLPs) and DQw3 (DQ beta 3a and DQ beta 3b RFLPs). By sequential use of a short DQ alpha cDNA probe a second, DQ alpha allelic series is defined by RFLP. This series correlates to a lesser extent than DQ beta RFLPs with the HLA-DQ serological specificities. Thus, two DQ alpha RFLPs correlate with a single DQ serotype (DQ alpha 1a and DQ alpha 1c with DQw1), but three DQ alpha RFLPs correlate with more than one DQ serotype (DQ alpha 1b with DQw1 and DQw3; DQ alpha 2 with DQw2 and DQw3; DQ alpha 3 with DQw2 and DQw3). Individual DQ beta and DQ alpha RFLP subtypes appear to correlate with single, or associated HLA-DR specificities. Specific combinations of DQ beta with DQ alpha RFLPs also correlate with HLA-Dw splits of DR2 and DRw6. A system for HLA-DNA typing is described, which uses RFLP patterns generated by sequential hybridization of TaqI-digested DNAs with short DR beta, DQ beta and DQ alpha cDNA probes. The DQ beta and DQ alpha probes not only identify the DQ allele, but because of linkage disequilibrium with DR, help to assign the DR allele, which may not always be identified with a DR beta probe alone. PMID- 2889138 TI - Identification and characterization of Thy-1 homologues from bovine thymocytes. AB - Two forms of Thy-1 homologues of apparent mol. wt of 25,000 (designated BTp25) and 45,000 (designated BTp45) were isolated from bovine thymocyte membrane by solubilization, affinity chromatography with Con A, and preparative SDS-PAGE. Both forms reacted with a rabbit antiserum to murine Thy-1 in an enzyme-linked immunosorbent assay (ELISA). BTp45 is most likely a dimer of BTp25, since the two are indistinguishable in their amino acid compositions. Comparison of amino acid compositions of BTp25 and BTp45 to that of rodent and human Thy-1 by the S delta Q index revealed significant relatedness among these molecules. BTp25 and BTp45 demonstrate more structural homology to rodent Thy-1 than to human Thy-1. Detailed chemical analyses indicate that bovine Thy-1 homologues contain neutral sugars and fatty acids covalently bound to the polypeptide chain; therefore, they are lipoglycoproteins. PMID- 2889139 TI - Complementary DNA for a human subgroup IV immunoglobulin lambda-chain. AB - We have cloned a cDNA (p3C4 lambda 5) encoding a human immunoglobulin lambda chain of human-mouse heterohybridoma, H6-3C4, which produces a human monoclonal antibody against human sperm surface antigen. Amino acid sequence deduced from the nucleotide sequence of V lambda (V lambda 3C4) of cloned cDNA was closely related to that of SHV lambda protein, a member of subgroup IV. Southern blot analysis of human genomic DNAs by using V lambda 3C4 as a probe detected at least 8 cross-hybridizing members of subgroup V lambda IV. Restriction enzyme fragment polymorphism (RFLP) appeared to be present in normal individuals with V lambda 3C4 gene. PMID- 2889140 TI - Mutagenic evaluation of etintidine (BL-5641), a novel histamine H2-receptor antagonist, using the chromosome aberration test in CHL cells and the micronucleus test in mice. AB - The mutagenic effects of etintidine (BL-5641), a novel histamine H2-receptor antagonist, was assessed using the chromosome aberration test in CHL cells and the micronucleus test in mice. (1) Etintidine did not show any chromosome aberrations in the presence or absence of S9 mix at any concentration tested. (2) Etintidine did not increase the frequency of micronuclei in polychromatic erythrocytes even at the dose of 50% of the LD50 at single (24 h) and chronological preparation after drug administration. PMID- 2889141 TI - Medical and surgical treatment for unstable angina. PMID- 2889142 TI - The adherence of Escherichia coli to the intestinal epithelium of piglets. AB - The ability of some pathogenic strains of E. coli to adhere to the intestinal epithelium significantly enhances their effectivity. This adhesion of particular pigs' strains is mediated by specific pili possessing the K 88 antigen found on the outer membrane of the bacterial cell. In in vitro experiments with isolated piglets' enterocytes, a considerable adherence of the E. coli K 88+ strain was found when compared with the same bacterial strain but lacking this plasmid directed antigen. Comparable results were obtained in in vivo experiments with ligated intestinal loops as well as with monoassociated piglets. Furthermore, the adherence ability is most pronounced at the early postnatal period and is negligible in adult pigs. PMID- 2889143 TI - Two forms of transforming growth factor-beta distinguished by multipotential haematopoietic progenitor cells. AB - Type-beta transforming growth factors (TGF-beta s) are polypeptides that act hormonally to control proliferation and differentiation of many cell types. Two distinct homodimeric TGF-beta polypeptides, TGF-beta 1 and TGF-beta 2 have been identified which show approximately 70% amino-acid sequence similarity. Despite their structural differences, TGF-beta 1 and TGF-beta 2 are equally potent at inhibiting epithelial cell proliferation and adipogenic differentiation. The recent immunohistochemical localization of high levels of TGF-beta in the bone marrow and haematopoietic progenitors of the fetal liver has raised the possibility that TGF-beta s might be involved in the regulation of haematopoiesis. Here we show that TGF-beta 1, but not TGF-beta 2, is a potent inhibitor of haematopoietic progenitor cell proliferation. TGF-beta 1 inhibited colony formation by murine factor-dependent haematopoietic progenitor cells in response to interleukin-3 (IL-3) or granulocyte-macrophage colony stimulating factor (GM-CSF), as well as colony formation by marrow progenitor cells responding to CSF-1 (M-CSF). The progenitor cell lines examined were approximately 100-fold more sensitive to TGF-beta 1 than TGF-beta 2, and displayed type-I TGF-beta receptors with affinity approximately 20-fold higher for TGF-beta 1 than TGF-beta 2. These results identify TGF-beta 1 as a novel regulator of haematopoiesis that acts through type-I TGF-beta receptors to modulate proliferation of progenitor cells in response to haematopoietic growth factors. PMID- 2889144 TI - Germline mosaicism and Duchenne muscular dystrophy mutations. AB - Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disease with an incidence of approximately 1 in 3,500 newborn boys. The DMD locus has a high mutation frequency: one third of the cases is thought to result from a new mutation. Linkage studies using probes to detect restriction fragment length polymorphisms and DNA deletion studies have greatly improved DMD carrier detection and prenatal diagnosis. Here we report on two families in which a pERT87 (DXS164) deletion was transmitted to more than one offspring by women who showed no evidence for the mutation in their own somatic (white blood) cells. We also show that the deletion in both siblings in one of the families is identical, indicating that the deletion must have occurred during mitosis in early germline proliferation, leading to a germline mosaicism. This phenomenon may turn out to be a major factor contributing to the induction of DMD mutations, and has important implications for the counselling of DMD families. PMID- 2889145 TI - A partial deletion of the muscular dystrophy gene transmitted twice by an unaffected male. AB - A gene of unknown function located in band Xp21 on the short arm of the human X chromosome gives rise to X-linked recessive muscular dystrophy, of either Duchenne or Becker type, when mutated. The gene encodes a large muscle-specific transcript of about 14 kilobases (kb) and its genomic size extends over more than 1,800 kb. The high mutation rate (about 10(-4) per generation) is likely to result from the large target size. Submicroscopic deletions, detectable with one or more of the dozen cloned DNA probes available for regions within the gene, constitute a significant proportion of the mutations. Because no such deletions have been found in normal individuals, it is assumed that intragenic deletions are the molecular basis of the mutations. The origin of deletions can be traced in families. With sufficient data collected, it will soon be possible to answer questions about the relative frequencies of mutations in male and female gametogenesis and about the timing of mutational events in mitotic or meiotic stages of germ cell development. We have studied a four generation family containing males who have Duchenne muscular dystrophy due to deletion of the sequence recognized by intragenic probe J-Bir. The deletion was present in two of five daughters of a woman who herself did not have the deletion. Haplotype analysis on 15 members of this family using nine informative restriction fragment length polymorphism (RFLP) markers indicated that the J-Bir deletion chromosome was transmitted from the unaffected father. PMID- 2889146 TI - Critics denounce first genome map as premature. PMID- 2889147 TI - Indian health planners shun insecticides in disease control. PMID- 2889148 TI - Direct detection of more than 50% of the Duchenne muscular dystrophy mutations by field inversion gels. AB - Duchenne muscular dystrophy (DMD) is an X-linked disorder affecting about 1 in 3,500 males. It is allelic with the milder Becker muscular dystrophy. The biochemical basis for both diseases is unknown and no effective treatment is available. Long-range physical mapping has shown that the DMD gene, localized in Xp21, is extremely large, exceeding 2 million base pairs. Until now, carrier detection and prenatal diagnosis has involved the use of linked restriction fragment length polymorphism markers which detect muscular dystrophy-associated deletions in about 10% of the cases. Field inversion gel electrophoresis (FIGE) allows the detection of structural rearrangements in 21 out of 39 of the DMD patients studied (54%), of which 14 (65%) were not detected by conventional methods. Large deletions seem to make up a much higher fraction of the DMD mutations than so far indicated by other methods. A region prone to deletion was located in the distal half of the gene. FIGE analysis could provide a valuable extension of information for carrier detection and prenatal diagnosis. The technique should be generally applicable to the study of diseases involving structural chromosomal rearrangements. PMID- 2889149 TI - [Takayasu's disease as the cause of myocardial infarct in an infant]. PMID- 2889150 TI - [Epidemiology of AIDS and HIV infections in the Netherlands; current status and prognosis for 1987-1990]. PMID- 2889151 TI - [Salazosulfapyridine or 5-aminosalicylic acid]. PMID- 2889152 TI - [Acute abdomen caused by torsion of an undescended testis]. PMID- 2889153 TI - Ultrastructural evidence for gamma aminobutyric acid-immunoreactive synapses on somatostatin-immunoreactive perikarya in the periventricular anterior hypothalamus. AB - Somatostatin-immunoreactive perikarya in the periventricular anterior hypothalamus were demonstrated to be surrounded by gamma aminobutyric acid GABA immunoreactive nerve terminals, by combining pre-embedding immunocytochemistry for somatostatin and gold labelling post-embedding immunocytochemistry for GABA. Ultrastructural studies revealed that in each 100-nm section, cells immunoreactive for somatostatin (n = 62) were contacted by a mean of 7.6 +/- 0.4 terminal profiles of which 3.0 +/- 0.3 (40%) were GABA-immunoreactive. Most GABA immunoreactive terminals contained clear rounded vesicles and, where synaptic specializations were well demonstrated, appeared to be symmetric. The finding provides evidence that there is a significant GABA input to somatostatin neurons, an observation strengthening the hypothesis that GABA may inhibit somatostatin neurons, thereby causing increased secretion of growth hormone. PMID- 2889154 TI - Frontiers in neuropharmacology. Introduction to the session on modulators. PMID- 2889155 TI - Is dopamine a transmitter in the periphery? AB - There is now substantial experimental evidence supporting the hypothesis that a dopaminergic neuronal system is present in peripheral tissues. This evidence includes identified and characterized dopaminergic receptors, the presence of relatively large concentrations of dopamine and DOPAC in some neurons and organ systems, and the differential loss of norepinephrine or dopamine following treatment with catecholaminergic neurotoxins. There are still many studies that remain to be completed, however, existing evidence is consistent with a peripheral dopaminergic neuronal system. PMID- 2889156 TI - Evolving concepts on the interactions between antidepressant treatments and monoamine neurotransmitters. AB - Most research on the mechanism of action of antidepressant drugs and repeated electroconvulsive shock (ECS) has focussed on changes in monoamine chemistry and function. Most antidepressant treatments, on repeated administration, decrease the number of beta-adrenoceptors in the cortex, a change which does not occur if 5-HT pathways to the cortex are lesioned, suggesting that 5-HT neurones play a permissive role in the change and high-lighting the complex neurotransmitter interactions that are present. Several drugs and electroconvulsive shock also attenuate the function of alpha 2-adrenoceptors (shown both by the sedation response and change in MOPEG-SO4 that occurs after injection of clonodine). Repeated treatment with the majority of antidepressant drugs decreases the number of 5-HT2 receptor and function. However, repeated electroconvulsive shock increases both these parameters. In contrast the hypothermic response which follows injection of the 5HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin-(8-OHDPAT) is attenuated not only after a range of diverse antidepressant drugs but also electroconvulsive shock. This suggests that the 5HT1A receptor is subsensitive after both antidepressant drugs and electroconvulsive shock. Recently, it has been demonstrated that a wide range of antidepressant drugs and electroconvulsive shock lead, on repeated administration, to an increase in the number of GABAB receptors and the enhancement of the degree of inhibition of release of 5-HT in cortical slices by the GABAB agonist baclofen suggests that a functional correlate of this change can be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889157 TI - Adrenaline in the CNS: in vivo evidence for a functional pathway innervating the hypothalamus. AB - This article reviews the evidence, obtained from studies employing the technique of intracerebral dialysis, to monitor changes in extracellular adrenaline in the hypothalamus, that adrenaline is released from nerve endings in the hypothalamus and has a functional role. Studies using [3H] adrenaline to determine the specificity of uptake mechanisms for adrenaline indicate that labelled adrenaline is also taken up by noradrenergic nerve endings. This supports the need to develop techniques to monitor changes in endogenous release of adrenaline. In this study, it has been shown that inhibition of phenylethanolamine-N methyltransferase selectively decreases tissue levels in the hypothalamus and in vivo release of adrenaline, while monoamine oxidase inhibition and antagonism of alpha 2-adrenoceptors increases the release of both adrenaline and noradrenaline. The "selective" noradrenergic neurotoxin DSP4 caused an initial increase in the release of both catecholamines, followed by a marked decrease in their release. Stimulation of the adrenaline-containing neurones in the rostral ventrolateral medulla (C1 region) increased the release of adrenaline in the posterior hypothalamus, but not that of noradrenaline, while also increasing mean arterial blood pressure. Pharmacological evidence indicates that B2-adrenoceptors in the hypothalamus and the spinal cord are involved in the rise in mean arterial pressure, as the response is reduced by a selective B2-antagonist (ICI 118551). The rise in mean arterial blood pressure during C1 stimulation is enhanced by the alpha 2-antagonist idazoxan, supporting observations that alpha 2-adrenoceptors are involved in the pre-synaptic regulation of release of adrenaline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889158 TI - Behavioral pharmacology of central nervous system stimulants. AB - Central nervous system stimulants can be distinguished on the basis of their differential effects in various behavioral tests. There are sufficient differences between these drugs to suggest that one could develop CNS stimulants with more selective behavioral actions. PMID- 2889159 TI - Chronic pharmacological manipulation of dopamine receptors in brain. AB - Dopamine receptors in the brain play an important role in the treatment of schizophrenia and in the development of tardive dyskinesia. In Parkinson's disease the loss of dopamine innervation and the use of chronic administration of L-DOPA or therapy with dopamine agonists also affects the function of dopamine receptors in brain. Subacute administration of neuroleptic drugs to rodents for a few weeks followed by the withdrawal of the drug induces supersensitivity of dopamine receptors in the striatum. However, the long-term administration of neuroleptic drugs to rodents shows that typical neuroleptic drugs can induce functional supersensitivity of dopamine receptors despite continued administration of drug. In contrast, atypical neuroleptics such as sulpiride, do not appear to induce the same changes in the activity of dopamine receptors. The functional supersensitivity of dopamine receptors produced by repeated administration of neuroleptic is reflected in changes in cholinergic, gamma aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT) and peptide neuronal systems. Chronic treatment of parkinsonian patients with drugs may obscure the changes in the function of dopamine receptors caused by the disease process. However, chronic administration of L-DOPA to normal rats and to rats with a unilateral lesions of the nigrostriatal pathway induced with 6-hydroxydopamine does not produce a down-regulation of the number of dopamine receptors. Rather, these experiments indicate the development of a functional supersensitivity of dopamine receptors in the absence of any obvious change in the nature of dopamine receptor populations in brain. In conclusion, while pharmacological manipulation, using neuroleptic drugs, produces the expected development of receptor supersensitivity, studies involving chronic treatment with agonists suggests that dopamine receptors do not always respond as would be predicted. It appears that there are aspects of the regulation of dopamine receptors in brain following pharmacological manipulation which remain to be resolved. PMID- 2889160 TI - Behavioural and ECoG spectrum power effects after intraventricular injection of drugs altering dopaminergic transmission in rats. AB - In rats with cannulae permanently implanted into the third cerebral ventricle, the effects of different pharmacological manipulations affecting dopaminergic mechanisms, were studied on behaviour and electrocorticographic (ECoG) activity, continuously quantified in its spectrum power. The intraventricular injection (0.1-1 nmol) of (-)3PPP[3-(3-hydroxyphenyl) N-n-propylpiperidine], a specific agonist at dopamine (DA) autoreceptors, produced dose-dependent behavioural sedation or sleep and an increase in ECoG spectrum power, with a predominant increase in the lower frequency bands. Short episodes of stereotyped movements, wet-dog syndrome, penile grooming and erection were also observed. Similar behavioural and ECoG effects were elicited by the intraventricular injection of R (+)-8-chloro-2,3,4,5-tetrohydro-3-methyl-5-phenyl-1H-3-benzazepi ne-7-ol (SCH 23390), a selective antagonist at D1 postsynaptic receptors, although these were preceded by a short period of behavioural and sexual stimulation. In addition, the intraventricular administration of some neuroleptics, chloropromazine and haloperidol, produced behavioural and ECoG slow wave sleep. No significant changes were observed with a neuroleptic drug, 1-sulpiride, which is reputed to act selectively as an antagonist at dopamine D2 receptors. In conclusion, the present experiments add new evidence in favour of the idea that dopaminergic mechanisms are involved in mammalian species in the control of arousal and that both post-synaptic D1 and D2 receptors may take part in such a control. PMID- 2889161 TI - Effects of continuous administration for 12 months of amine-depleting drugs and chlorpromazine on striatal dopamine function in the rat. AB - Rats received either chlorpromazine (33-36 mg/kg/day), oxypertine (6.3-7.3 mg/kg/day), tetrabenazine (6.0-6.7 mg/kg/day) or reserpine (0.28-0.30 mg/kg/day) continuously for up to 12 months. Chlorpromazine and tetrabenazine reduced spontaneous locomotor activity of animals after 1 month of treatment. Thereafter, locomotor activity in animals treated with chlorpromazine returned to control levels, whereas treatment with tetrabenazine increased locomotion. Oxypertine enhanced spontaneous locomotor activity after 9 months of administration only, whereas treatment with reserpine did not alter this activity at any time during the study compared to age-matched controls. Treatment with tetrabenazine enhanced stereotyped behaviour induced by apomorphine (0.063-1.0 mg/kg s.c.) throughout the study. In contrast, stereotypy in animals administered chlorpromazine, oxypertine or reserpine was the same as in control animals throughout the 12 months of treatment. Levels of dopamine in the striatum were reduced after the first month of administration of chlorpromazine, but thereafter returned to control values. Treatment with oxypertine for up to 12 months did not alter concentrations of dopamine in the striatum, whereas administration of tetrabenazine and reserpine caused a decrease. All treatments with drugs consistently reduced the content of homovanillic acid in the striatum during the study. The Bmax for specific binding of [3H]spiperone in the striatum was increased by continuous treatment of animals with chlorpromazine, oxypertine or tetrabenazine, although the effects of oxypertine and tetrabenazine were only transient. Administration of reserpine did not alter the Bmax for specific binding of [3H]spiperone. The Bmax for specific binding of [3H]piflutixol in the striatum was unchanged by any treatment for up to 12 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889162 TI - The effects of cortical ablation on multiple unit activity in the striatum following dexamphetamine. AB - Bilateral removal of the fronto-parietal cortex of the rat resulted in decreased spontaneous multiple-unit activity recorded in the striatum of freely-moving rats. Cortical ablations changed the neuronal response in the striatum to systemic administration of dexamphetamine (2.5 mg/kg i.p.) from excitation in control animals (88%) to inhibition in ablated animals (61%). Furthermore, catalepsy, induced by haloperidol, but not by morphine, was markedly attenuated after cortical ablation. These changes were accompanied by a 23% decrease in the specific binding of [3H]spiperone in the striatum. The binding of [3H]met enkephalin was unaffected by the cortical lesions. Levels of glutamate in the striatum decreased from 8.88 +/- 0.5 mumols/g in control animals to 6.93 +/- 0.37 mumols/g after bilateral cortical ablation. On the other hand, cortical ablations did not alter the content of either the gamma-aminobutyric acid or glutamine of the striatum. It is concluded that the excitatory response, observed in striatal neurons in freely-moving animals, is dependent upon an intact cerebral cortex and requires intact cortico-striatal afferents. The results further suggest that neurons in the striatum are under the tonic influence of glutamate, released from cortico-striatal afferents. Lastly, some dopamine D2 binding sites in the striatum are located on cortico-striatal afferent terminals and blockade of these striatal D2 sites may be involved in the induction of catalepsy by neuroleptic drugs. PMID- 2889163 TI - Inhibition of [3H][3-MeHis2]thyrotropin releasing hormone recognition sites in the rat brain by tifluadom, a kappa opiate receptor agonist. AB - The effect of tifluadom (TIF), a postulated kappa-opiate agonist with a benzodiazepine (Bz) structure, on the binding of [3H][3-MeHis2]thyrotropin releasing hormone [( 3H]MeTRH) to receptors for thyrotropin releasing hormone (TRH) in membranes from rat brain was determined. Tifluadom inhibited the binding of [3H]MeTRH with an IC50 value of 1.88 microM. When the binding was carried out in the presence of an IC20 concentration of tifluadom, the Bmax value of [3H]MeTRH was decreased by 20% but no change in the Kd value was noted, indicating that the inhibition was apparently noncompetitive. Ro 15-1788 a benzodiazepine antagonist, as well as bicuculline, a gamma-aminobutyric acid (GABA) antagonist did not antagonize the effect of tifluadom on the binding of [3H]MeTRH suggesting that the benzodiazepine receptors are not involved in the action of tifluadom. Since tifluadom is suggested to be a kappa-opioid agonist, the effect of other kappa-opiate ligands were also tested for their ability to affect TRH receptors. The drugs used were ethylketocyclazocine, dynorphin(1-13) and 5-bromo-6-(2-imidazoline-2-ylamino)quinoxaline (U-50,488H). The order of potency of these compounds to inhibit the binding of [3H]MeTRH to membrane from the rat brain was in the following order: tifluadom greater than U-50,488H greater than dynorphin-(1-13) greater than ethylketocyclazocine. It is concluded that tifluadom inhibits the binding of [3H]MeTRH to receptors in brain in a noncompetitive manner. The effect does not appear to be mediated through benzodiazepine receptors but possibly through kappa-opiate receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889164 TI - Involvement of catecholaminergic neurones and alpha-adrenoceptors in the wet-dog shake and forepaw licking behaviour produced by the intrathecal injection of an analogue of thyrotrophin-releasing hormone (CG 3509). AB - Intrathecal injection of the analogue of TRH, CG 3509, into conscious rats produced dose-related wet-dog shakes and forepaw licking, which showed a bell shaped relationship of intensity to dose. Pretreatment with alpha-MPT intraperitoneally, markedly reduced levels of noradrenaline and dopamine in the spinal cord and brainstem and attenuated both CG 3509-induced responses, while intrathecal treatment with DSP4 selectively reduced noradrenaline in the spinal cord without affecting either behaviour. Since denervation supersensitivity may develop following treatment with DSP4, these results are not inconsistent with a proposal that bulbospinal noradrenergic neurones modulate the behaviour induced by CG 3509. Wet-dog shakes and forepaw licking induced by CG 3509 were reduced by pretreatment with phenoxybenzamine or prazosin, suggesting that a tonic noradrenergic pathway may facilitate both behavioural responses through alpha 1 adrenoceptors. Methoxamine, combined with CG 3509 partially attenuated the wet dog shake behaviour, but methoxamine produced marked hindlimb jerking which might physiologically antagonise wet-dog shakes. Concomitant administration of clonidine and CG 3509 potently reduced wet-dog shakes in a dose-related manner but did not significantly affect forepaw licking, while idazoxan did not significantly affect either response. The latter findings imply that alpha 2 adrenoceptors play different roles in modulating the two behavioural responses and the possible synaptic location of the receptors is discussed. Taken together these results suggest that CG 3509 may release noradrenaline from bulbospinal neurones regulating motor function. PMID- 2889165 TI - Noradrenaline-induced emesis. Alpha-2 adrenoceptor mediation in the area postrema. AB - The emetic action of noradrenaline was investigated in unanesthetized cats, after it was injected into the cerebral ventricles through chronically implanted cannulae. Intracerebroventricular injection of noradrenaline produced dose dependent and shortlasting emesis, which was abolished after ablation of the area postrema. However, copper sulphate, given orally, evoked emesis in cats with an ablated area postrema. The selective alpha-2 adrenoceptor antagonist, yohimbine, as well as the mixed alpha-1 and alpha-2 adrenoceptor blocking drugs, phentolamine, tolazoline, phenoxybenzamine and dihydroergotamine, but not the selective alpha-1 adrenoceptor antagonist, prazosin, all injected into the cerebral ventricles, attenuated or blocked the emesis evoked by intracerebroventricular injection of noradrenaline. Of the alpha-adrenoceptor antagonist, only yohimbine produced dose-dependent inhibition of the emesis induced by noradrenaline. On the contrary, selected beta-adrenoceptor blocking agents, an antimuscarinic drug, a ganglionic blocking agent, an antihistamine, dopamine antagonists and a 5-hydroxytryptamine antagonist, all injected into the cerebral ventricles, had no significant effect on the emesis induced by noradrenaline, similarly injected. The emetic response to intracerebroventricular injection of noradrenaline, as well as to intragastric administration of copper sulphate was not altered in cats pretreated with intracerebroventricular injections of alpha-methyl-p-tyrosine and bretylium. On the other hand, the emetic response to intracerebroventricular injection of noradrenaline and to intragastric administration of copper sulphate was attentuated or blocked in cats pretreated with reserpine intracerebroventricularly. Moreover, in cats pretreated with intracerebroventricular injection of 6-hydroxydopamine and hemicholinium, the emesis induced by intracerebroventricular administration of noradrenaline but not that produced by intragastric injection of copper sulphate, was depressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889166 TI - Effects of ketamine and (+)cyclazocine on 4-aminopyridine and "magnesium free" epileptogenic activity in hippocampal slices of rats. AB - The effects of ketamine and (+)cyclazocine on three in vitro models of epilepsy: the "Mg2+ free", the 4-aminopyridine (4-AP) and, for comparison, the penicillin model were studied. These data indicate that the two compounds had an inhibitory effect in hippocampal slices of rats, bathed in "Mg2+ free" solution at a concentration that did not influence the basal field potential. They also had an inhibitory effect on the penicillin model, but at concentrations ten times greater than those effective against "Mg2+ free" model. On the other hand, (+)cyclazocine was equally active against epileptogenic activity produced by 4-AP and "Mg2+ free" solution, while ketamine failed to produce an effect on epileptiform activity induced by 4-AP. PMID- 2889167 TI - (1S,2R)-5-methoxy-1-methyl-2-(n-propylamino)tetralin ([+]-AJ-76) elevates transmitter synthesis in dopaminergic neurons surviving a partial nigrostriatal lesion. AB - (+)-AJ-76 is a novel compound with a spectrum of actions suggesting that it is a selective antagonist of dopamine (DA) autoreceptors. In animals with partial lesions of the dopaminergic nigrostriatal system, in which DA synthesis of surviving neurons was elevated, (+)-AJ-76 further increased DA synthesis above levels produced by the lesion alone. This finding suggests that (+)-AJ-76 might be of value in the treatment of Parkinson's disease. PMID- 2889168 TI - An overview of medically related problems in the cold environment. PMID- 2889169 TI - [Controlled clinical evaluation of 2 hypnotic triazole benzodiazepines, estazolam and triazolam, used the night before surgical interventions]. AB - In order to study the efficacy of estazolam versus triazolam in preoperative patients, two groups of 49 patients each were treated with 2 mg estazolam and 0.5 mg triazolam in a single dose, the night before surgery. This controlled study was designed to evaluate sleep patterns, emotional status on awakening and side effects, by the administration of a questionnaire either in the morning of the day before (baseline) or on the morning of surgery. The results show better sleep patterns after estazolam excepting the duration of sleep that was the same for the two drugs. The better emotional status upon awakening in the morning before surgery and the lower incidence of side effects in the patients treated with estazolam, lead to the conclusion that estazolam is clearly better than triazolam in the treatment of preoperative patients. PMID- 2889170 TI - In vitro evaluation of the activity of Entamoeba histolytica studies on motility. AB - The tube migration test for leukocyte function studies has been modified to test the motility of Entamoeba histolytica. The test was more sensitive to the effect of antiamebic drugs than was a test for phagocytic activity. A 50% reduction in amebic motility was seen instantly after exposure to metronidazole (40 mg/l). A similar reduction of phagocytosis at the same concentration of the drug was seen only after two hours' preexposure. The extent of amebic migration in the test tube is dependent on factors such as concentration of parasites, temperature and incubation time. The tube migration test is cheap and simple and could be a valuable supplement to existing screening methods for potential antiamebic drugs. PMID- 2889171 TI - AMPA is a powerful neurotoxin in the chicken retina. AB - Intravitreal (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazoleacetic acid (AMPA) is a powerful excitotoxin on the chicken retina. Doses of 10 nmol/eye produce half maximum destruction of cholinergic amacrine cells, making AMPA equipotent with kainic acid. The effects of AMPA can be distinguished from those of kainic acid morphologically, and from those of N-methyl-D-aspartic acid by the failure of 2 amino-5-phosphonopentanoic acid (2-AP5) to block those of AMPA. Both morphologically, and in response to 2-AP5, the effects of AMPA and quisqualic acid are indistinguishable, but AMPA is much more potent than quisqualic acid, presumably due to the uptake and inactivation of quisqualic acid. PMID- 2889172 TI - L-glutamate and N-methyl-D-asparatate actions on membrane potential and conductance of cat abducens motoneurones. AB - The actions of L-glutamate and N-methyl-D-aspartate (NMDA) were studied with intracellular recordings from cat abducens motoneurones. Amino acids were electrophoresed extracellularly from the same 7-barreled electrode types as those used in the spinal cord. Depolarization development, conductance changes and firing pattern induced by amino acids were very similar to those described for spinal motoneurones. The shape of NMDA depolarization suggests a uniform distribution of the involved receptors on the membrane of the motoneurone. PMID- 2889173 TI - Regional distribution of the membrane-bound pyroglutamate amino peptidase degrading thyrotropin-releasing hormone in rat brain. AB - The brain regional distribution of membrane-bound pyroglutamate aminopeptidase degrading thyrotropin-releasing hormone (TRH) in rat was studied using a specific radiometric assay. The distribution was not homogeneous: a 10-fold difference was observed between regions. The highest activity was detected in olfactory bulb while the lowest was in the cervical part of spinal cord. There was no correlation with the regional distribution of enzyme activity vs TRH levels, previously reported TRH receptors or in vitro TRH release. The differential distribution of this enzyme is consistent with the hypothesis that it is responsible for extracellular degradation of neuroactive peptides. PMID- 2889174 TI - Spider toxin blocks excitatory amino acid responses in isolated hippocampal pyramidal neurons. AB - Using the 'concentration-clamp' technique we have investigated the action of Joro spider toxin (JSTX), as a specific blocker of glutamate receptor, on freshly isolated rat hippocampal pyramidal neurons. The neurons showed prominent responses to L-glutamate (L-Glu), quisqualate (QA) and kainate (KA) and JSTX blocked completely the both responses. The blocking action of toxin was dose dependent at the concentrations of toxin between 4.8 X 10(-12) and 4.8 X 10(-8) M, and was remarkably similar in cell to cell trials. The kinetics of blockade was revealed by applying the toxin to the non-desensitizing KA response. We suggest that the JSTX spider toxin may be a valuable tool in ligand binding studies of QA/KA receptors in the central nervous system. PMID- 2889175 TI - Is neurotransmitter histamine predominantly inactivated in astrocytes? AB - Rat synaptosomes and astroglia cell-enriched fraction were tested for the uptake of histamine (HA) and its precursor histidine, and the activities of the HA synthesizing enzyme, histidine decarboxylase (HD) and HA-metabolizing enzyme, histamine methyltransferase (HMT). While histidine uptake was more active into synaptosomes than into astrocytes, only astrocytes were capable of a significant HA uptake. Kinetic analysis of the astrocytic HA uptake revealed a high affinity low capacity system (Km = 5 X 10(-7) M, Vmax = 1.6 X 10(-12) mol.min-1 X mg-1) similar to the astroglial transport systems for other neurotransmitters. HMT was 70% more active in astrocytes than in synaptosomes, whereas HD activity was not different in these two preparations. The results indicate that astrocytes could be the major site of neurotransmitter HA inactivation. PMID- 2889176 TI - [The homeo box: facts and hypotheses]. AB - A review of the published data pertaining to studies of homeo box, a homologous DNA sequence found in genomes of various organisms. The following aspects of this important phenomenon are considered: expression of homeo box-containing genes, pattern of their organization, localization of corresponding proteins, possible function of proteins, evolution of homeo box. PMID- 2889177 TI - Knowledge of diabetic retinopathy before and 18 years after the Airlie House Symposium on Treatment of Diabetic Retinopathy. AB - In 1968, The Airlie House Symposium evaluated the current knowledge of the natural history of diabetic retinopathy. The effects of tight metabolic control, pituitary ablation, and photocoagulation were discussed at length. Xenon arc photocoagulation was the mainstay of therapy and was usually applied focally to individual patches of new vessels. Photocoagulation of background retinopathy was rarely done. Panretinal photocoagulation was in its infancy, the ruby laser was newly introduced, there were no data on the use of the argon laser, and automated vitrectomy had not been introduced. Participants in the symposium set the stage for the acquisition of valid clinical data from which important therapeutic conclusions have subsequently been drawn by (1) summarizing the areas of consensus and disagreement, (2) devising a standard classification of diabetic retinopathy, and (3) proposing controlled clinical trials for unanswered questions. PMID- 2889178 TI - [Somatostatin therapy in acute pancreatitis]. PMID- 2889179 TI - [Demonstration of seasonal changes of circadian rhythms of amikacin chrononephrotoxicity in rats]. AB - The present study investigates the chronobiological approach of the amikacin induced nephrotoxicity in rats treated with a single sublethal dose administered at different times of day. The nephrotoxicity is appreciated by gamma-glutamyl transferase and N-acetyl-beta-D-glucosaminidase urinary excretion, respectively a brush border and a lysosomal enzyme. These excretions peak out at 14:00 and reach a through at 20:00. In contrast, in a precedent experimentation, in october/november, we evidence gamma-glutamyl-transferase excretion increased at 20:00. So, we evidenced with amikacin not only a circadian but also a seasonal susceptibility in rats. PMID- 2889180 TI - [Chrononephrotoxicity of amikacin after 7-day chronic poisoning in rats]. AB - We have studied the chrononephrotoxicity of amikacin during and after a prolonged treatment in rats. Animals received by intramuscular route a daily dose of 400 mg/kg during 7 days at four different times (08:00, 14:00, 20:00 or 02:00). Large time-dependent variations in renal injury had been evidenced by several parameters and particularly by enzymuria. This injury is maximal when administration is made at 14:00. These data confirmed results obtained in previous investigations. The knowledge of chrononephrotoxicity could permit an optimization of drugs in clinics. PMID- 2889181 TI - Testicular undescent and torsion. AB - The higher the testis resides above the scrotum, the more dysgenetic the morphology is likely to be. High testes are rarely responsive to HCG and should be treated by orchiopexy by the age of 2 to 3 years. The undescended testis does not mature normally after the age of 2 years and may produce adverse effects on the contralateral descended testis, possibly by an autoimmune mechanism. A course of HCG for boys with low-lying undescended testes, both unilateral and bilateral, may produce descent in as many as 15 per cent of patients and may make the technical aspects of orchiopexy easier in those who do not respond. Unilateral cryptorchid testes that are dysplastic or located high should generally be removed before adolescence. PMID- 2889182 TI - Hyposecretion of beta-adrenergically induced sweating in cystic fibrosis heterozygotes. AB - In order to determine if expression of the cystic fibrosis gene can be detected in heterozygotes, we determined sweat responses induced by local stimulation with cholinergic and beta-adrenergic agents for 20 heterozygotes, 19 age- and sex matched controls, and five subjects with cystic fibrosis. Active sweat glands were counted and sweat droplets were collected in constant bore capillaries and measured optically. Each subject was tested two to six times. The central finding was that the sweat response of carriers was significantly lower than controls to beta-adrenergic stimulation (p = 0.0013, two-tailed t test; p less than 0.02, Mann-Whitney U), while cystic fibrosis homozygotes did not sweat at all. In contrast, the cholinergic sweat responses did not differ between carriers and controls. For both groups the correlation between cholinergic and beta-adrenergic sweating was positive, but a linear regression of beta-adrenergic sweat responses as a function of cholinergic sweat responses yielded slopes that were significantly different for the two groups. The ratio of beta-adrenergic to cholinergic sweating was plotted for each subject; the mean ratio of the carriers was approximately half of the mean for the controls (p = 0.0002 using t test or p less than 0.002 using the Mann-Whitney U). Our results confirm previous studies and provide new evidence that carriers have, on average, a beta-adrenergically stimulated secretory response that is significantly reduced relative to the control response. PMID- 2889184 TI - CF1ATPase beta- and epsilon-subunit genes are separated in the sweet potato chloroplast genome. PMID- 2889183 TI - A mouse homeobox containing gene on chromosome 11: sequence and tissue-specific expression. AB - We have molecularly cloned a mouse homeobox containing gene by isolating cDNA and genomic clones. The gene is located in a previously described cluster on chromosome 11 (Hart et al. (1985) Cell 43, 9-18) and was identified as the Hox2.3 gene. We present the complete mRNA sequence of this gene and describe similarities to other homeobox containing genes, among which its human homologue, the cl gene. High expression of the Hox2.3 gene was found in kidney, testis, and spinal cord of adult mice, in the spinal cord of 12.5-17.5 day embryos and in differentiating EC cells depending on their treatment. Three different treatments of the pluripotent EC cell line P19, each leading to the induction of a specific differentiation pathway, resulted in all cases in induction of Hox2.3; however, major quantitative differences in this response were observed. PMID- 2889185 TI - Nucleotide sequence of the pilin gene from Bacteroides nodosus strain 238 (serogroup G). PMID- 2889186 TI - A second useful polymorphism for the cytosolic thymidine kinase gene (TK1) with the enzyme BstEII which will allow haplotying at this locus on chromosome 17 (q21 q22). PMID- 2889187 TI - A BamHI RFLP recognised by an anonymous chromosome 20 probe, p4.8 (D20S14). PMID- 2889188 TI - Sequence analyses of extrachromosomal Sau3A and related family DNA: analysis of recombination in the excision event. AB - Previously, we reported a recombination-prone human alphoid-like repetitive DNA (Sau3A family) which is characterized by abundance in the extrachromosomal fraction and restriction fragment length polymorphism. We suggested a specific homologous recombination to be responsible for the DNA excision from the chromosomes and also the sequence rearrangement in the chromosomes. In order to investigate the nature of the recombination further, 8 different clones were obtained which hybridized with Sau3A probe among over 1,500 extrachromosomal DNA clones. Restriction mapping and nucleotide sequence analyses showed two to be Sau3A monomers and dimers, four Sau3A recombinants, as observed previously, one a recombinant of the Sau3A-related sequence on chromosome 17, and one a new Sau3A related sequence. Sequence analyses of the recombination junctions in the recombinant clones indicated a specific homologous recombination also to be responsible for all but one clone. The molecular mechanism and biological significance associated with the recombination are discussed. PMID- 2889189 TI - A PPY cDNA clone identifies a frequent RFLP. PMID- 2889190 TI - An EcoRI polymorphism associated with a human genomic clone from band 11p13. PMID- 2889191 TI - Human gastrin (GAS) RFLP recognised by digestion with BamHI or EcoRI. PMID- 2889192 TI - A TaqI RFLP detecting single copy fragment (G80) from chromosome 7 p13-p15 (D7S373). PMID- 2889193 TI - Multiple Taq I RFLPs at the human manganese superoxide dismutase (S0D2) locus on chromosome 6. PMID- 2889194 TI - BamHI RFLP at the insulin-like growth factor II (IGF2) locus on chromosome 11. PMID- 2889195 TI - Human natriuretic peptides (ANP) gene locus: BsmI RFLP. PMID- 2889196 TI - Two polymorphisms in the human lipoprotein lipase (LPL) gene. PMID- 2889197 TI - Human cDNA probe (OL167,D21S109) detects RFLP on chromosome 21. PMID- 2889198 TI - TaqI polymorphism in the human LDL receptor gene. PMID- 2889199 TI - Effect of porcine gastrin releasing peptide on gastric secretion and motility and the release of hormonal peptides in conscious cats. AB - The effect of porcine gastrin releasing peptide (GRP) was compared to those of bombesin (BBS) and pentagastrin (PG) in conscious cats. GRP and BBS augmented acid and pepsin secretions, as well as antral motility with an early effect comparable to that produced by pentagastrin with an elevation of low amplitude contractions and a diminution of high amplitude contractions. BBS and GRP increased plasma gastrin and pancreatic polypeptide (PP) levels and decreased motilin levels measured by a C terminus-directed antiserum. In all cases, BBS and GRP displayed parallel dose-response curves. PG showed slight differences in the slopes of the dose-response curves slopes of the dose-response curves except for acid secretion stimulation where no difference was noted (PG was the most effective) and for pepsin stimulation where the difference was large (PG was much less effective). According to the different targets studied, BBS was 4 to 9 times more potent than GRP, 6 to 200 times more than PG. Gastrin release, elicited by the lowest ED50 of both BBS and GRP, should be considered as their primary effect in the cat. PMID- 2889200 TI - Met-enkephalin concentrations in striatum respond reciprocally to alterations in dopamine neurotransmission. AB - The striatum is richly innervated by both enkephalinergic and dopaminergic neurons, providing an anatomic framework from which intimate functional interrelationships between these neuronal systems may be postulated. Accordingly, many functional processes within dopamine neurons have been shown to be modulated by opioid peptides. In the present study we confirm predictable reciprocal effects in enkephalin neurons, brought about by modification of dopamine neurotransmission. Dopamine receptor blockade reliably increased striatal Met enkephalin concentrations by about 50%, whereas chronic treatment with a potent long-acting dopamine receptor agonist was necessary to demonstrate a small 10-20% decrease in Met-enkephalin concentrations. Depletion of presynaptic dopamine also resulted in a marked 50-60% augmentation of Met-enkephalin levels, that could be prevented by concomitant treatment with a dopamine analogue. Increasing dopamine turnover and release by a mu-opioid agonist decreased Met-enkephalin concentrations, as might have been predicted. Thus we have shown a marked dopaminergic influence that maintains striatal Met-enkephalin concentrations by near maximal tonic inhibitory effects. PMID- 2889201 TI - Immunohistochemical localization of aminopeptidase M in rat brain and periphery: relationship of enzyme localization and enkephalin metabolism. AB - An antiserum specific for rat aminopeptidase M has been used for the immunohistochemical localization of the enzyme in rat brain and peripheral tissues. The enzyme in brain is localized exclusively on blood vessels. Within the pituitary the enzyme was associated with the vasculature in the posterior lobe, on the surface of the intermediate lobe and on the surface of some cells in the anterior lobe. In the liver, fine cell staining was observed between parenchymal cells, in the ileum the entire lumenal surface was stained, while in the kidney both proximal tubular and a central tubular staining was detected. In each tissue aminopeptidase M is localized such that it can limit diffusion across specific barriers. Aminopeptidase M activity in brain has been proposed to function in the degradation of synaptically released enkephalins. Its localization on blood vessels requires that enkephalins diffuse prior to degradation, a concept not in concert with current hypotheses. Based on these studies it is proposed that diffusion away from enkephalinergic synapses plays a key role in terminating enkephalin action. PMID- 2889202 TI - Opiate peptide receptor types on cultured mouse spinal neurons. AB - mu, delta and kappa opioid receptor agonists, morphiceptin, Leu-enkephalin and dynorphin reduced monosynaptic EPSPs evoked in spinal cord neurons by stimulation of spinal cord neurons in a mouse cell culture system. The incidence of the cell pairs which responded to morphiceptin, Leu-enkephalin and dynorphin was 3%, 63% and 37% respectively. Statistical analysis showed the effect of Leu-enkephalin was presynaptic. When tested with Leu-enkephalin and dynorphin, 6 cell pairs responded to both Leu-enkephalin and dynorphin, 5 cell pairs only responded to Leu-enkephalin, none of the cell pairs responded only to dynorphin (n = 18). It is suggested that some cells have only delta receptors, but kappa receptors coexist with delta receptors. Opiate receptors of the mu type are rare on SC neurons. PMID- 2889203 TI - Morphological studies on the effect of taxol on cultured human prostatic cancer cells. AB - The effect of taxol, an experimental antitumor drug, was studied in vitro on human prostatic cancer cells. Different concentrations of taxol, varying from 5 microM to 0.01 nM, were used. The effect of taxol was examined by light and electron microscopy. Taxol had a marked cytotoxic effect on prostatic cancer cells down to a 10 nM concentration of taxol when observed by light microscopy. However, by electron microscopy, the specific effect of taxol was seen even with a 1 nM concentration of taxol. Taxol induced the appearance of numerous round cells after a few days and, subsequently, progressive death of the tumor cells. Among the surviving tumor cells, large tumor cells were noted as well as many multinucleated tumor cells. By electron microscopy, the round tumor cells showed mitotic figures with a high amount of cytoplasmic microtubules. Nonmitotic cells were often multinucleated and contained a high number of cytoplasmic microtubules and microtubule-related structures. The results show that taxol, even at very low concentrations, has a highly cytotoxic effect on prostatic cancer cells; and when a very low concentration of taxol is used with no obvious cytotoxic effect at the light microscopic level, specific taxol-induced ultrastructural alterations can be observed. PMID- 2889204 TI - [Factors in sudden and non-sudden death after myocardial infarction]. AB - Attempts at preventing total and sudden cardiac death after myocardial infarction can only succeed if its mechanisms and its contributing of determinant factors are known. It is now well established that sudden deaths account for one-half of mortality cases and that in the vast majority of cases these deaths are due to malignant ventricular arrhythmia. Several sudden death risk factors have been identified, including ventricular dysrhythmias, left ventricular dysfunction and myocardial ischaemia. A number of therapeutic trials on the prevention of post infarction death have been conducted, but so far only beta-blockers have proved effective in reducing the incidence of total and sudden cardiac death. It is permissible to think, however, that other, discerningly selected treatments might also be effective. PMID- 2889205 TI - [Microbial inhibitors of phospholipase C]. AB - Inhibitors of the Clostridium perfringens phospholipase C were prepared from the filtrates of the culture liquids of Streptomyces saracetidus and Streptomyces species using soluble and cross-linked polyelectrolytes. The technological scheme of isolation involves ultrafiltration. The inhibitors produced by the two strains had different chemical nature. The preparation obtained from Str. saraceticus was proved to be a complex of inhibitors that were separated by gel-chromatography into a major polypeptide with a molecular weight of 5500-6500 and a low-molecular weight glycopeptide. The inhibitor obtained from Str. species was found to be a high-molecular weight protein. PMID- 2889206 TI - [Hypogonadotropic hypogonadism combined with anosmia (Kallmann's syndrome)]. AB - Diagnosis in Kallmann's syndrome is often erroneous and results in the administration of inadequate therapy. The aim of the study was to define characteristic features of a course of disease and to administer adequate therapy. It has been established that cases of Kallmann's syndrome are rather frequent. Patients with hypogonadism should be examined with respect to anosmia because such a combination suggests the diagnosis of Kallmann's syndrome. The selection of a therapeutic method should be strictly individual bearing in mind a degree of hypoplasia and the presence of cryptorchism. In the combination of Kallmann's syndrome with cryptorchism CG therapy results in the elimination of cryptorchism without surgery in most patients. Chorionic gonadotropin should be administered in combination with androgens in marked testicular hypoplasia in any period at the reproductive age; later on it can be only chorionic gonadotropin. Correct diagnosis and adequate therapy lead to sex and social rehabilitation of patients with Kallmann's syndrome decreasing the number of sterile men. PMID- 2889207 TI - [Functional interrelations of monoamines, thyrotropic hormone and thyroid hormones in hyperprolactinemia]. AB - Functional interrelationships of serotonin, dopamine, prolactin, TRH and thyroid hormones in patients with hyperprolactinemia were studied. Altogether 26 patients with amenorrhea in hyperprolactinemia without clinical signs of disorder of thyroid function were examined. The levels of serotonin and dopamine were determined by spectrofluorimetry, the level of hormones was determined by a radioimmunoassay. An increase in the level of serotonin and a decrease in the level of dopamine in all the patients, a decrease in TRH and T4, and an increase in T3 were noted. The levels of monoamines, TRH and thyroid hormones showed correlation. It has been concluded that disorder of the monoaminergic mechanisms of regulation creates conditions for the rearrangement of hormonal interrelationships in the neuroendocrine functional system and determines the involvement of the hypophyseothyroid system in the pathological process. Therefore patients with hyperprolactinemia are at risk of developing thyroid functional disorders. PMID- 2889208 TI - Region-specific expression of mouse homeobox genes in the embryonic mesoderm and central nervous system. AB - The homeobox is a 180-base-pair sequence characteristically found in homeotic and segmentation genes in Drosophila. Several copies of homeoboxes are also found in the mammalian genome, but it is not known whether these are components of morphogenetic loci in mammals as well. As a step toward understanding the function of mammalian homeoboxes, we have used in situ hybridization to define the spatial pattern of expression of two mouse homeobox genes in the midgestational mouse embryo. The two mouse homeoboxes studied here, Hox 1.2 and Hox 1.4, are located 20 kilobases apart on mouse chromosome 6. Our results demonstrate the following: (i) Hox 1.2 transcripts are localized mainly in the posterior myelencephalon, in the cervical central nervous system (CNS), and in several thoracic prevertebrae; (ii) Hox 1.4 transcripts are localized mainly in the posterior myelencephalon and in the cervical CNS; (iii) within the CNS region expressing Hox 1.4, the level of Hox 1.4 transcripts is higher in the mantle layer than in the ependymal layer and higher in the dorsal than in the ventral area. The specific localization of Hox 1.2 and Hox 1.4 transcripts in the embryonic CNS and the restricted pattern of expression along the rostrocaudal axis are strikingly reminiscent of the expression pattern of Drosophila homeoboxes in the fly embryo and larvae. Despite the different developmental strategies adopted by Drosophila and mammals, functional similarities may exist between Drosophila and mammalian homeobox genes. PMID- 2889209 TI - The Florey lecture, 1987. Corticomotoneuronal projections: synaptic events related to skilled movement. AB - During infancy, children develop an expanding repertoire of movement skills in parallel with the maturation in their brains of direct nerve-fibre connections between the cerebral cortex and motoneurons in the spinal cord. These corticomotoneuronal connections are characteristic of primates and can be studied in monkeys; in these animals, refinement in the control of movements of the hand is also associated with increasing development of corticomotoneuronal connections. In monkeys, motoneurons innervating distally acting muscles are preferentially excited by convergent activities in corticomotoneuronal fibres. This excitation has been demonstrated to be effective in natural functional states when a conscious monkey is performing learned movement tasks. Extensive intraspinal arborizations of individual corticomotoneuronal fibres could permit the engagement of large numbers of local motoneurons and related interneurons by each of these fibres. Abolition of corticomotoneuronal influences, after section of the pyramidal tracts, causes a permanent deficit in fractionation of use of muscles of the forelimb and an inability to carry out independent movements of the fingers. PMID- 2889210 TI - Alpha ganglion cells in mammalian retinae. AB - Retinae from species of six orders of mammals (table 1) were processed by an on the-slide neurofibrillar staining method to establish whether alpha-type ganglion cells are generally present in placental mammals. Alpha cells of the domestic cat, where they were first defined as a type, are used as a standard of reference. Alpha cells were found in all the twenty species examined; characteristically they have the largest somata and large dendritic fields with a typical branching pattern. In keeping with the common morphology there are inner and outer stratifying subpopulations and therefore a presumptive 'on-centre' and 'off-centre' responsiveness to light. Depending on the species, alpha cells form between 1 and 4% of the ganglion-cell population and their dendritic fields cover the retina three to four times. The morphology of alpha ganglion cells, and many of their quantitative features, are conserved in mammals coming from different habitats and having a wide variety of behaviours. Because it is known different habitats and having a wide variety of behaviours. Because it is known from the cat that alpha ganglion cells have brisk-transient or Y receptive fields it is possible that all placental mammals possess this physiological system. PMID- 2889211 TI - Direct and relayed projection of periodontal receptor afferents to the cerebellum in the ferret. AB - Field potentials in the cerebellar cortex of the ferret have been studied in response to stimulation of alveolar, muscular and cutaneous branches of the trigeminal nerve. Responses from the alveolar nerves are unusual in their very short latency. Evidence based on latency analysis, frequency following and comparison with other well-known inputs supports the view that the earliest field potentials are due to direct, unrelayed afferents, which terminate as mossy fibres. There is, in addition, a monosynaptically relayed afferent path via mossy fibres. The alveolar nerve afferents concerned with the direct projection are shown to come from periodontal mechanoreceptors and not from cutaneous receptors. No such connections are found from jaw-muscle spindle afferents. The direct and relayed periodontal pathways are both ipsilateral and crossed. They terminate in the cerebellar cortex in the parvermal region of lobules IV, V and VI. The functional significance of the direct periodontal afferent projection is considered particularly in the light of parallels with the vestibular system, which also has direct and relayed cerebellar projections. PMID- 2889212 TI - Focal synaptic potentials due to discrete mossy-fibre arrival volleys in the cerebellar cortex. AB - The previously described direct and relayed projections of periodontal afferents to the cerebellar cortex have been examined in detail by extracellular field potential analysis. Advantage is taken of the very small temporal dispersion of the afferent volleys to permit identification of the presynaptic spike potential of mossy fibres, the subsequent synaptic potential and the firing of granule cells. Changes in form of the presynaptic potential with depth are compared with published descriptions of presynaptic potentials elsewhere. The negative synaptic potential in the granular layer is shown to have a positive aspect in the molecular layer. Granule-cell firing can, under some conditions, yield a population spike interrupting the synaptic potential wave. Records are presented showing all-or-none complex waves, which appear to be single glomerular potentials, not previously described in the mammalian cerebellum. Their distinction from cellular spike potentials is emphasized. PMID- 2889213 TI - The effects of catecholamines on tension reactivation in cardiac muscle. AB - The effects of adrenaline and the beta-agonist isoprenaline on the time course of tension reactivation were studied in several cardiac tissues. The aim of the study was to assess whether experimental evidence can be found for a role of the sarcoplasmic reticulum in the reactivation of tension. It was assumed that calcium recycles between different parts of the reticulum, and that this recycling may affect tension repriming. Isoprenaline was assumed to enhance such recycling by increasing the uptake of calcium, following its release during a preceding contraction. Isoprenaline (in the range of 40 nM to 4 microM) was found to enhance tension repriming in adult guinea pig atria. However, in adult rat atria, isoprenaline often gave a complex effect, with a smaller degree of repriming at short intervals, and enhanced repriming at longer intervals. This was thought to reflect the balance between the enhancing effect of the drug on calcium recycling and an augmented release from the sarcoplasmic reticulum (SR). In striking contrast, there was no effect of isoprenaline on tension repriming in neonatal guinea pig atria and a retardation in neonatal rat atria. This was interpreted as reflecting the lack of a sarcoplasmic network in the neonatal tissue. The effects of isoprenaline on tension repriming in the frog atrium (which also has a sparse sarcoplasmic reticulum network) were also found to be complex; low concentrations (40 nM) enhanced the process, and high concentrations (0.4 microM) retarded it. Intermediate levels often produced a 'crossover' effect: more reactivation at short intervals, and less at long intervals. The interpretation of these results was that there are two processes which interact to determine the amount of tension produced at short intervals after each contraction: the basal reactivation process and some augmenting mechanism superimposed on it. This mechanism is probably related to other behavioural features of cardiac muscle, such as rate-dependent increases in membrane calcium currents. It is relevant mainly in those cases where tension repriming depends on membrane calcium currents. Further experiments (in the frog atrium) with elevated calcium and with the alpha-adrenergic agonist phenylephrine (both of which slowed down the reactivation process) also support this idea. These agents elevate internal calcium levels, and presumably saturate the augmenting mechanism (by producing maximal tension responses).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2889214 TI - Spatial properties of neurons in the monkey striate cortex. AB - Contrast sensitivity as a function of spatial frequency was determined for 138 neurons in the foveal region of primate striate cortex. The accuracy of three models in describing these functions was assessed by the method of least squares. Models based on difference-of-Gaussians (DOG) functions where shown to be superior to those based on the Gabor function or the second differential of a Gaussian. In the most general case of the DOG models, each subregion of a simple cell's receptive field was constructed from a single DOG function. All the models are compatible with the classical observation that the receptive fields of simple cells are made up of spatially discrete 'on' and 'off' regions. Although the DOG based models have more free parameters, they can account better for the variety of shapes of spatial contrast sensitivity functions observed in cortical cells and, unlike other models, they provide a detailed description of the organization of subregions of the receptive field that is consistent with the physiological constraints imposed by earlier stages in the visual pathway. Despite the fact that the DOG-based models have spatially discrete components, the resulting amplitude spectra in the frequency domain describe complex cells just as well as simple cells. The superiority of the DOG-based models as a primary spatial filter is discussed in relation to popular models of visual processing that use the Gabor function or the second differential of a Gaussian. PMID- 2889215 TI - Current concept for improving treatment of prostate cancer based on combination of LH-RH agonists with other agents. PMID- 2889216 TI - A.P.U.D. type endocrine tumour of the prostate. Incidence and prognosis in association with adenocarcinoma. PMID- 2889217 TI - Antihistaminic treatment of allergic rhinitis: a double-blind study with terfenadine versus dexchlorpheniramine. AB - A double-blind study was carried out in 65 patients with seasonal rhinitis to compare the effectiveness and tolerance of terfenadine and dexchlorpheniramine. Patients were allocated at random to receive treatment for 1 week with either 60 mg terfenadine twice daily or 2 mg dexchlorpheniramine maleate 3-times daily. Before and after treatment, patients underwent RAST and skin prick tests for reactivity to pollen and those who were positive also had rhinomanometric measurements made of nasal resistance. Diary cards were used by patients to record the severity of nasal obstruction, rhinorrhoea, sneezing, watery, irritated and red eyes, itching of the nose, throat and eyes, and cough. Details were also kept of the frequency and severity of any side-effects. Pollen counts were taken daily during the treatment period. The results showed that both terfenadine and dexchlorpheniramine produced good or excellent relief of the main symptoms in 78% and 73% of the patients, respectively. There was no significant correlation between the pollen count and reduced symptom severity. Both drugs produced a reduction in total nasal resistance but this was not significantly different from initial values, neither was there a significant difference between treatment. Terfenadine was well tolerated and side-effects incidence was significantly lower (p less than 0.01) than in patients treated with dexchlorpheniramine, particularly so with reference to drowsiness. PMID- 2889218 TI - Long term administration of some antipsychotic drugs increases body weight and feeding in rats. Are D2 dopamine receptors involved? AB - Long term administration of the antipsychotic drugs thioridazine, trifluoperazine, haloperidol, and sulpiride increased body weight in rats. This effect was found to be sex dependent, that is, while female rats were prone to gain weight, male rats did not. Chlorpromazine and fluphenazine decreased body weight in male rats but did not affect females. The mechanism of body weight gain was investigated with sulpiride. A linear relationship between dose of sulpiride and body weight gain was found. Also, sulpiride increased caloric intake, and both actions were counteracted by bromocriptine, a specific D2 receptor agonist. These results confirm that antipsychotic drugs affect feeding and body weight and suggest that hyperphagia and body weight gain might be mediated by blockade of dopamine receptors of the D2 type. PMID- 2889219 TI - Novel benzodiazepine receptor ligands stimulate intake of hypertonic NaCl solution in rehydrating rats. AB - Experiments were conducted to determine the degree of generality of previous findings that anxiolytics increased the ingestion of hypertonic saline in rehydrating rats. Further, potential differential effects amongst recently described benzodiazepine receptor partial agonists were explored. Finally, the hypothesis that benzodiazepine receptor partial inverse agonists would decrease the ingestion of hypertonic NaCl solution was tested. Results indicated that full agonists (midazolam, ZK 93423, zopiclone) produced substantial dose-related increases in hypertonic saline consumption. The putative 5-HT1A agonist, buspirone, produced only a dose-dependent decrease in saline intake. Partial agonists fell into two distinct categories: ZK 91296, CL 218,872 and two novel benzodiazepines, Ro16-6028 and Ro17-1812, also increased saline ingestion. In contrast, two pyrazoloquinolines, CGS 9896 and CGS 9895, had no significant effect on intake. Two compounds, CGS 8216 and FG 7142, described as benzodiazepine partial inverse agonists, did not significantly affect consumption of the hypertonic saline. PMID- 2889220 TI - Effect of clonidine on consummatory negative contrast and on novelty-induced stress. AB - In Experiments 1 and 1a rats were shifted from 32% to 4% sucrose solutions. The resultant negative contrast effect in consummatory behavior was not alleviated by clonidine (3.12, 6.25, 12.5, 25.0 and 50.0 micrograms/kg). The lower dose of the drug had no effect on behavior, the higher doses reduced consumption in shifted and unshifted rats in a dose dependent fashion. In Experiment 2 clonidine (6.25, 12.5 micrograms/kg) raised plasma glucose levels in a dose dependent fashion when the animals were exposed to a novel environment. These results are at variance with those obtained with chlordiazepoxide (and other anxiolytics in the case of contrast effects) and suggest limits on the degree to which clonidine can be considered to function as an anxiolytic. PMID- 2889221 TI - The effect of MDA and MDMA ("Ecstasy") isomers in combination with pirenpirone on operant responding in mice. AB - The behaviorally disruptive effects of the optical isomers of 1-(3,4 methylenedioxyphenyl-2-aminopropane) (MDA) and its N-methyl derivative (MDMA) were evaluated in 27 mice trained to bar-press for a liquid food reinforcement. In addition, a second study was conducted in which mice were pretreated with either saline or the 5-HT-2 antagonist, pirenpirone, prior to the administration of either MDMA or MDA using the same behavioral procedure. The results indicated that the behaviorally disruptive effects produced only by R(-)-MDA, but not those of S(+)-MDA, R(-)-MDA, nor of S(+)-MDMA, were significantly attenuated by pirenpirone. These findings support previous research findings which indicate that this isomer may be producing its behaviorally disruptive effects via an action on 5-HT-2 receptors. PMID- 2889222 TI - Adenosine modulates the dopaminergic function in the nigro-striatal system by interacting with striatal dopamine dependent adenylate cyclase. AB - Behavioral and pharmacological evidences suggest that dopaminergic mechanisms in striatum might be counteracted by adenosine or potentiated by its pharmacological antagonists methylxanthines. To test whether adenosine modulation of the dopaminergic function could be, at least in part, due to an interaction at the level of the adenylate cyclase complex, we studied the effects of the adenosine analog R-Phenyl-isopropil-adenosine (R-PIA) on basal and dopamine-sensitive adenylate cyclase in rat striatum. R-PIA, which interacts with both adenosine A1 inhibitory and A2-stimulatory receptors, dose-dependently inhibited the stimulation induced by dopamine, and seemed to utilize the same pool of enzyme linked to dopaminergic D1 receptors. Two experimental approaches leading to supersensitivity of striatal dopaminergic receptors, (i.e., 6-hydroxy-dopamine injection in substantia nigra and reserpine administration) also induced upregulation of adenosine-dependent adenylate cyclase in striatum, and altered R PIA modulation of dopamine-sensitive adenylate cyclase. Conversely, after subchronic treatment with neuroleptics such as haloperidol or sulpiride, upregulation of 3H-Spiroperidol binding in striatum was not associated with changes of R-PIA dependent adenylate cyclase in this area. It is concluded that adenosine might modulate post-synaptic responses to dopamine via adenosine receptors which functionally interact with dopaminergic D1 receptors in striatum. PMID- 2889223 TI - Postsynaptic effects of alpha agonists on adrenoceptors of the reserpinized rat vas deferens. AB - The activities of the alpha-1 antagonist prazosin and alpha-2 antagonist yohimbine were evaluated against noradrenaline (NA), methoxamine (Me) and clonidine (Clo) on the reserpinized rat vas deferens. Prazosin antagonized competitively Me but not NA and Clo. On the other hand yohimbine showed a low and not competitive antagonism towards all the three agonists. Similar results were obtained when the antagonistic activities were tested in the presence of the alternative antagonist, in the attempt to isolate a single receptor population. We can conclude that the smooth musculature of the rat vas deferens contains prevalently alpha-1 adrenoceptors and a small population of NA activated receptors resistant to alpha-2 antagonists. PMID- 2889224 TI - Biosensors. A discussion. 28 and 29 May 1986. PMID- 2889225 TI - Amperometric enzyme electrodes. AB - Three different types of amperometric enzyme electrode are described. The first type uses a conducting organic-salt electrode to oxidize NADH. Results for sensors for ethanol and for bile acids are presented. In the second type of sensor, flavoenzymes are directly oxidized on the surface of the conducting organic-salt electrode. Results for five different enzymes are described. The mechanism of the enzyme oxidation is discussed and the reaction is shown to take place by heterogeneous redox catalysis and not by homogeneous mediation. The enzymes are strongly adsorbed on the electrode; microelectrodes for in vivo studies can be constructed without a membrane. Results for in vivo studies of changing glucose levels in the brain of a freely moving rat are presented. The third type of sensor is designed to measure low levels of toxic gases such as H2S and HCN. This is done by monitoring the inhibition by the toxic gas of the activity of the respiratory enzyme cytochrome oxidase. PMID- 2889226 TI - Immunosensors. AB - The current trends and future aspects of the research and development of immunosensors are overviewed. A non-labelled immunosensor, whose selectivity depends on immunochemical affinity of an antigen for its corresponding antibody, has been developed as the basis for the potentiometric determination of an antigen, with an antibody-bound membrane or electrode. Non-labelled immunosensors for syphilis antibody, blood typing, human chorionic gonadotropin (HCG), and human serum albumin have been investigated. In contrast with non-labelled immunosensors, labelled immunosensors may be characterized by marked enhancement of sensitivity. Of these labelled immunosensors, enzyme immunosensors that use the chemical amplification of a labelling enzyme for sensitivity are promising. Enzyme immunosensors with an oxygen electrode have been developed to determine AFP, HCG, IgG and toxin. Bioaffinity sensors with a preformed metastable ligand receptor complex, which are similar to the enzyme immunosensor have been found effective for the determination of thyroxine (T4), biotin, and insulin. PMID- 2889227 TI - Electrochemical immunoassays. AB - Immunoassays are routinely used to detect, specifically, low levels of many antigens. The trend away from the use of radioisotopic labels has resulted in a proliferation of alternative labels, many of which have electrochemical activity. The more successful of these assays have used enzyme labels, coupled with amperometric or potentiometric methods of detection of the products. A number of assays have also been designed which are specifically electrochemical in origin, not simply adaptations of currently used spectrophotometric methods. Much effort has been expended in developing a potentiometric immunoassay that measures the change in potential that should occur when an antibody binds to its antigen. The use of electroactive labels has resulted in a number of assays for drugs. The advantages of an enzyme-linked mediated assay for lidocaine, an antiarrhythmic drug, are discussed. PMID- 2889228 TI - Optical biosensors for immunoassays: the fluorescence capillary-fill device. AB - This paper reports, for the first time, details of a novel type of optical biosensor for immunoassays, the fluorescence capillary-fill device (FCFD). This is based on a straightforward adaptation of the technology used to mass manufacture liquid-crystal display (LCD) cells to give cheap disposable immunosensors. These merely require contact by the sample to give a result in about a minute, and use certain principles of optical fibres and waveguides to avoid the need for operator attention, for physical separation methods or for washing steps. After a very brief introductory review and classification of optical biosensors, the main features of the FCFD and its associated instrumentation are described. The optical characteristics of the FCFD are then described, followed by accounts of the immunoassay method, the measurement system used in the experiments, the fabrication of FCFD sensors and a detailed description of the design of a competitive immunoassay for human immunoglobulin G (hIgG). The experimental details and the results of a first attempt at such an assay are then presented and discussed. It is concluded that the demonstration of this assay is a significant achievement, because the format of the FCFD, its manufacturing process and its instrumentation are completely novel. Certain problem areas have been identified and quantified; intended further work on these is outlined. PMID- 2889229 TI - Microelectrodes in medicine. AB - The chief applications of microelectrodes in medicine are in experimental studies of tissue and cell behaviour and of metabolism. Microprobes have been developed for a wide range of specific substrates and for the detection of bioelectric potentials. They have provided information that now forms the basis of much of our understanding of biological phenomena. Their inherent characteristics, such as fragility and 'drift', render them unsuitable for general clinical application except at the surface of organs. The heterogeneity of tissues makes it necessary to specify the exact anatomical location of microelectrode measurements and the probes themselves must be of a form that neither distorts, damages, nor stimulates reactions from, the cells or blood vessels with which they are in contact. PMID- 2889230 TI - Biosensors in process control. AB - Improvement in bioprocess control will require development of monitors for a wide range of cell-growth and downstream-process parameters. These requirements are examined in terms of the development and application of biosensor devices and physical measurement techniques. Acoustic, dielectric and laser light scattering techniques are discussed primarily as monitors and analysers for biomass parameters. Developments with biosensor devices are discussed in terms of their application in membrane sampling-flow analysis probes and the potential of more direct biosensing principles. PMID- 2889231 TI - Introduction to the principles and applications of biosensors. AB - A biosensor is an analytical device that responds to an analyte in an appropriate sample and interprets its concentration as an electrical signal via a suitable combination of a biological recognition system and an electrochemical transducer. As a result of recent scientific and technological progress, such devices are likely to play an increasingly important role in generating analytical information in all sectors of human endeavour, from medicine to the military. In particular, biosensors will form the basis of cheap, simple devices for acquiring chemical information, bringing sophisticated analytical capabilities to the non specialist and general public alike. The market opportunities for the rapid exploitation of novel developments in this sector are substantial. Biosensor research is also likely to have a significant impact on the development of modern electronics. PMID- 2889232 TI - Structure and electrochemistry of oxidoreductases. AB - The principles on which Nature has developed multifunctional redox centres, covering a large range of potentials, protected from water and oxygen and surrounded by highly specific proteins, are demonstrated. Structures and accessibilities of the active sites of iron-sulphur proteins, sulphur proteins, flavoproteins, cytochromes and copper proteins are correlated with their possibilities and modes of electron exchange with natural partners, artificial mediators and (modified) electrodes. The participation of charge-transfer and tunnelling processes in electron transport is demonstrated, and a suitable relative orientation of the partners is recognized as one of the most important requirements for electrochemical communication between large molecules and electrodes. The use of specifically modified electrode surfaces, for example those based on electroconductive polymers, is proposed as one of the aspects of future developments for direct electron transfer to proteins. PMID- 2889233 TI - Enzyme electrodes and their application. AB - Starting from the state of the art, principles for improving the analytical characteristics of enzyme electrodes are discussed. Coupling of appropriate amperometric electrode processes with enzyme systems, e.g. urease or aminopeptidases, results in a simplification of operation. Optimal sample frequencies are realized on the basis of enzyme membranes, with both a small characteristic diffusion time and a high enzyme activity, applied in a well designed sample-processing system. Coupled enzyme reactions of the sequence or competition type are successfully used for extension to new analytes, e.g. inhibitors, cofactors or alternative substrates. Cyclization of the analyte enhances the sensitivity of enzyme electrodes to the nanomolar concentration range. Enzymic anti-interference layers are a tool for improving the sensor specificity. The operational characteristics of enzyme electrodes are thus adaptable to any given analytical problem. PMID- 2889234 TI - Electron-transfer biosensors. AB - The electrochemistry of redox proteins is now well established. Conditions exist which allow electron-transfer reactions of all simple proteins to proceed rapidly and reversibly at electrodes. Coupling of the electrode reaction to enzymes, for which the redox proteins act as cofactors, allows exploitation of this good electrochemistry. This is well illustrated by the enzyme-catalysed electrochemical oxidation of p-cresol to p-hydroxybenzaldehyde, which has been shown to proceed along with coupling to the electrode via the copper protein, azurin, or the organometallic compound ferroceneboronic acid. Ferrocene derivatives, in general, show a degree of versatility, coupling the electron transfer reactions of many enzymes. Thus derivatives of the ferricinium ion act as excellent electron-transfer reagents from the enzyme glucose oxidase. The system is capable of detecting glucose in blood. Similar procedures, in conjunction with the appropriate enzyme, have yielded assays for, among others, H2O2 and cholesterol. PMID- 2889235 TI - Alcohol, acetaldehyde and salsolinol-induced alterations in functions of cerebral GABA/benzodiazepine receptor complex. AB - Effects of alcohol (ethanol) and acetaldehyde on the metabolism and function of primary cultured GABAergic neurons and that of salsolinol, a condensation product of acetaldehyde with dopamine, on cerebral GABA/benzodiazepine (BZP) receptor complex were investigated. In vitro addition of acetaldehyde induced a significant reduction not only on the content of GABA but also on the basal and GABA-activated [3H]flunitrazepam ([3H]FLN) bindings in primary cultured neurons. In contrast, alcohol exhibited only suppressive effects on [3H]FLN binding as well as on the enhancement of [3H]FLN binding by GABA. On the other hand, salsolinol showed a significant stimulatory effect on [3H]FLN binding to cerebral particulate fractions obtained from alcohol-untreated mice in the presence of NaCl. Although a similar activation of cerebral [3H]FLN binding by salsolinol was found in alcohol-treated mice, this activation was significantly weaker in alcohol-withdrawn mice than those found in alcohol-untreated as well as alcohol inhaled mice. These results strongly suggest that acetaldehyde may have more important pathophysiological roles than those of alcohol in the exhibition of neurotoxicity during alcohol intake. The present results also suggest that salsolinol may have a modulatory role on cerebral benzodiazepine receptor and the decreased capacity of such a modulating mechanism may be involved in the exhibition of alcohol withdrawal syndrome, possibly by decreasing the function of endogenous ligands for benzodiazepine receptor in the brain. PMID- 2889236 TI - Serum dopamine beta hydroxylase activity and tardive dyskinesia. AB - A case-control study was done to test the effect of serum dopamine-beta hydroxylase (DBH) activity on tardive dyskinesia (TD) among 85 schizophrenic outpatients treated with neuroleptics. In contrast to the results of several previous studies, we found no significant association between serum DBH activity and the occurrence or severity of TD, controlling for other TD predictors. PMID- 2889237 TI - [Developments in the specialty of medical psychology--observed at the 4th Psychology in Medicine Congress of the Society for Medical Psychology, 15-17 May 1986, Berlin]. PMID- 2889238 TI - Polyarteritis and the kidney. AB - We report data on 43 patients with polyarteritis affecting the kidneys. The majority (41 patients) had renal histological evidence of microscopic polyarteritis. Although most patients (30 of 43) had significant renal impairment at the time of diagnosis (serum creatinine greater than 250 mumol/l) only five had a symptom, macroscopic haematuria, that directed attention to the kidneys. In the majority of patients in whom data was available there was rapid deterioration in renal function between presentation and diagnosis. Renal function at diagnosis was worse in patients aged over 50 of whom 20 out of 29 had a serum creatinine greater than 500 mumol/l compared with only four of 14 patients aged less than 50. The prognosis was worse in patients over 50 (41 per cent died), in patients with a serum creatinine higher than 500 mumol/l (54 per cent died) and in patients treated with intravenous methylprednisolone, (four also had intravenous cyclophosphamide) (38 per cent died). The major cause of death was sepsis and the actuarial one-year survival was 62 per cent. These results suggest that our approach to treatment should be modified towards lessening immunosuppression in older patients and in patients with renal failure at diagnosis. PMID- 2889239 TI - The molecular pathology of haemophilia. AB - The great success of recombinant DNA technology in unravelling the pathology of the thalassaemias at a molecular level has encouraged the application of these methods to other single gene disorders of man in the hope of gaining a deeper insight into the biochemical defects underlying them. An example of this approach is provided by the sex-linked recessive disorders of blood clotting: haemophilia and Christmas disease. These clinically indistinguishable, life-long disorders result from the deficiency or abnormality of the clotting proteins factor VIII and factor IX, respectively, which both participate in the activation of factor X in the intrinsic pathway of blood coagulation. This paper looks at the information concerning the molecular biology and pathology of the haemophilias which has recently been forthcoming. The genes for factor VIII and factor IX have both been successfully cloned within the past five years, with that of factor VIII, achieved in 1984, being a particular tour de force. It encompasses 0.1 per cent of the human X chromosome and is the largest gene yet characterised. Gene cloning is the starting point from which gene probes can be designed to elucidate the molecular pathology of the haemophilias. The implications of these discoveries for the practice of clinical medicine are reviewed, with special emphasis on prenatal diagnosis and carrier detection by means of restriction fragment length polymorphisms, and replacement therapy with recombinant factor VIII. PMID- 2889241 TI - Pharmacology and structure-activity relationships of alpha 2-adrenoceptor antagonists. PMID- 2889240 TI - Stem and stromal cell reconstitution of lethally irradiated mice following transplantation of hematopoietic tissue from donors of various ages. AB - If the limited life span of hematopoietic tissues in vitro is due to a finite proliferative capacity of individual stem cells, one might expect tissues of young donors to possess a greater proliferative capacity and to contain a larger population of primitive stem cells than those of older donors. To test this hypothesis, we used 12- and 8-day spleen colony formation (CFU-s) to assay more and less primitive stem cell subpopulations of three murine hematopoietic tissues: fetal liver (FL) and weanling (WBM) and adult (ABM) bone marrow. Subsequently, the same assays and a stromal cell assay were performed on the bone marrow from groups of lethally irradiated mice reconstituted with these tissues. Comparison of the CFU-s content of the donor tissues revealed that FL contained a significantly greater proportion of primitive stem cells as evidenced by a (Day 12):(Day 8) CFU-s ratio of 3.0 +/- 1.0 as compared to 0.9 +/- 0.1 for WBM and ABM. In addition, at 21 weeks post-transplantation the CFU-s/femur values of the FL reconstituted group were significantly greater than those of the ABM and WBM reconstituted groups. These results suggest that fetal hematopoietic tissue contains a greater proportion of primitive stem cells and has a greater proliferative potential than hematopoietic tissue from older donors. No differences were seen in stromal cell reconstitution of the three experimental groups. In all cases, assayable fibroblast colony forming cells (CFU-f) remained at 20-40% of control values, even at 21 weeks postreconstitution. PMID- 2889242 TI - Common structural features of drugs, transmitters and peptides in the central nervous system. PMID- 2889243 TI - Evidence of pili k88 and k99 as protecting antigens: immunization against enteric swine colibacillosis by sow vaccination. PMID- 2889244 TI - [Electromyographic study of the effects of vecuronium bromide compared with those of pancuronium, tubocurarine, fazadinium and suxamethonium]. PMID- 2889245 TI - [Urinary gamma-glutamyl transpeptidase as an index of renal tubular lesions during controlled hypotension produced by sodium nitroprusside]. PMID- 2889246 TI - [Acute pancreatitis]. PMID- 2889247 TI - [In vitro activity of mezlocillin on bacterial adhesion, phagocytosis and haemoagglutination of several anaerobic germs]. PMID- 2889248 TI - [Research on the formulation and quality evaluation of salazopyrine tablets]. PMID- 2889249 TI - Tardive dyskinesia syndrome in neuroleptic therapy. General considerations and clinical observations on forty cases investigated. PMID- 2889250 TI - Physiology of the upper urinary tract. PMID- 2889251 TI - [Pharmacodynamic effects of the beta-blocker mepindolol administered transdermally to healthy volunteers]. PMID- 2889252 TI - Mapping genes in juvenile myoclonic epilepsy. AB - The genetics of the various forms of epilepsy can be best understood by knowing where the affected gene is located. Genetic methodologies used to explore the genetics of epilepsy now include segregation analysis, linkage analysis and recombinant DNA technology. Juvenile myoclonic epilepsy (JME), a form of idiopathic epilepsy with a strong genetic component, provides informative pedigrees for linkage studies. Preliminary results demonstrate the heterogenous nature of the JME syndrome. PMID- 2889253 TI - [Neuropathies and almitrine. 14 cases]. AB - Previously reported cases of peripheral neuropathies occurring during almitrine therapy had only a few weeks follow-up after having stopped the drug. We have studied clinical and electrophysiological data 6 to 12 months after almitrine had been given up in 9 patients from a group of 14 whose epidemiologic, clinical, electrophysiological and pathological data had been registered. In 7 of them, without any chronic respiratory deficiency, almitrine was administered as almitrine bismesilate and raubasine, and in 7 others (6 with chronic respiratory deficiency) as almitrine bismesilate alone. In patients who had another possible cause of neuropathy, clinical disorders appeared after a lesser total quantity of almitrine (p less than 0.05). Clinical data were suggestive of sensory peripheral neuropathies of feet and lower third of legs. Electrophysiological data suggested distal axonopathy in spite of the absence of denervation: amplitudes of sensory potentials were reduced and nerve conduction velocities were moderately decreased. Biopsies revealed mild neurogenic atrophy of muscles and distal axonopathy. Clinical improvement was very slow and 6 to 12 months later, most of the patients still presented decreased vibration sense and ankle reflexes loss, but all of them were still improving. Amplitudes of sensory potentials and sensory nerve conduction velocities were significantly improved (p less than 0.05) but motor nerve conduction velocities were not (p greater than 0.05). Our study shows: 1) clinical, electrophysiological and pathological data similar to those previously reported; 2) subclinical disturbances of motor functions in lower limbs and sensory functions in upper limbs; 3) some patients presented with unusual signs: posture tremor (3 cases), painful legs and moving toes (1 case); 4) peripheral neuropathies may occur during almitrine therapy even in patients without any chronic respiratory insufficiency; 5) peripheral neuropathies occurred with lower doses in patients with other factors predisposing to neuropathies; 6) patients' improvement was very slow; 7) in 9 cases the imputability of these peripheral neuropathies to almitrine is plausible. We suggest not to prescribe almitrine without caution, especially in patients with other factors of neuropathy. Treatment should be regularly interrupted. PMID- 2889254 TI - Proceedings of a satellite symposium on famotidine: further developments in H2 receptor antagonist therapy. World Congresses of Gastroenterology meeting. Sao Paulo, Brazil, 12 September 1986. PMID- 2889255 TI - Comparison of once-daily bedtime administration of famotidine and ranitidine in the short-term treatment of duodenal ulcer. A multicenter, double-blind, controlled study. AB - A multicenter, double-blind, randomized, controlled study was conducted in 234 duodenal ulcer patients to compare the efficacy and safety of the H2-receptor antagonists famotidine and ranitidine in the treatment of duodenal ulcer. Patients received 40 mg famotidine (119 patients) or 300 mg ranitidine (115 patients) once daily at bedtime for 4 weeks. If ulcer lesions persisted, treatment was extended to 6 weeks. Efficacy was assessed by relief of symptoms and endoscopic findings of ulcer healing. Safety was determined on the basis of reports of side effects, results of laboratory tests, and, in selected patients, changes in plasma levels of hormones. The 4- and 6-week healing rates achieved with famotidine were 76% and 91%, respectively, and with ranitidine they were 76% and 87%, respectively; the differences in healing rates for the two drugs were not statistically significant. Similarly, both drugs provided satisfactory relief of pain and dyspeptic symptoms. However, famotidine produced significantly (P less than 0.05) greater relief of postprandial fullness and heartburn. The incidence of untoward effects was low in both treatment groups, and abnormal results in laboratory tests were observed in only one patient, a chronic alcoholic receiving famotidine, who withdrew from the study because of a slight elevation in serum transaminase levels. One patient in the ranitidine treatment group dropped out of the study because of a generalized urticarial rash; however, a causal relationship between drug and effect could not be established. The authors conclude that famotidine may be regarded as the best alternative to ranitidine in the treatment of duodenal ulcer. PMID- 2889256 TI - Famotidine: postmarketing clinical experience. AB - A postmarketing survey of famotidine usage (phase IV survey) tracked 6346 patients at 602 locations from August 1985 to April 1986. Through the survey, the efficacy and the safety of famotidine were studied. The patients included 4618 cases of peptic ulcer, 106 cases of reflux esophagitis, 1006 cases of upper gastrointestinal tract bleeding, 343 cases of bleeding and ulcer prophylaxis, and 273 cases of gastritis and other diseases, totalling 6346 patients. Efficacy was analyzed by type of disease in terms of overall improvement; results of intermittent hemostatic efficacy were obtained for upper gastrointestinal tract bleeding; and safety was assessed. Overall, the results were good; the 8-week healing rate was 92.4%, and 72.3% of patients had their bleeding controlled within 7 days of beginning famotidine therapy. Side effects occurred in only 0.43% of patients, and abnormalities in laboratory test results were observed in less than 1% of patients. Gastrointestinal side effects, especially constipation, occurred most frequently. Most side effects were mild. The results of this postmarketing survey indicate that famotidine is a safe and effective H2-receptor antagonist. PMID- 2889257 TI - Clinical benefits of intravenously administered famotidine in the treatment of upper gastrointestinal hemorrhage caused by peptic ulcer and stress ulcer disease. AB - Bleeding may stop spontaneously in mild or moderate cases of GI bleeding. Therefore, to prove that H2-receptor antagonists effectively stop GI bleeding, evaluation of the results of treatment in patients who are classified as severe cases by the Nagao taxonomy is needed. Data from the literature show that mortality is higher in patients with specific endoscopic findings, such as active bleeding, visible vessels, clot, or stain, than it is in patients without these findings. The criteria for establishing whether H2-receptor antagonists effectively control GI bleeding in severe cases include a reduction in mortality, in the rate of recurrent bleeding, or in the rate of emergency surgery. Data gathered from a current multicenter trial assessing the efficacy of 20 mg famotidine administered intravenously twice daily show that the rate of emergency surgery in patients with bleeding ulcer is 8.6%, which is substantially less than the 54.2% rate found in a retrospective review of patients treated before the introduction of H2-receptor antagonists. In addition, there were no deaths among famotidine-treated patients. Similarly, among patients with bleeding caused by stress ulcer, the percentage who were treated with famotidine and required emergency surgery was much less than that in the historical control group (15.8% versus 40.0%). Famotidine was effective in greater than or equal to 88% of patients with peptic ulcers and in 78.9% of patients with stress ulcers. Recurrent bleeding occurred more often in patients with exposed blood vessels. Intravenously administered famotidine is, therefore, effective for the control of GI bleeding caused by severe peptic ulcer and stress ulcer disease. PMID- 2889258 TI - Famotidine in the treatment of gastritis. AB - H2-receptor antagonists are widely used in the treatment of diseases such as gastric and duodenal ulcers, hemorrhage of the upper digestive tract, and the Zollinger-Ellison syndrome. However, the usefulness of H2-receptor antagonists in treating erosions and/or mucosal hemorrhages has not been established. A multicenter, double-blind, comparative trial was conducted to determine the effects of famotidine, a new H2-receptor antagonist, for such lesions. Patients received one of three oral doses (5, 10, or 20 mg) of famotidine twice daily for 2 weeks. The comparative efficacy and safety of the three dosages of famotidine in the treatment of lesions were evaluated, using an assessment of subjective symptoms, endoscopic findings, and adverse reactions. Symptoms, including epigastric pain, heartburn, and discomfort, were relieved in a substantial number of patients as early as 3 days after beginning treatment with famotidine. Moreover, less than 30% of patients complained of these symptoms after 2 weeks of famotidine therapy. There were no significant differences among the three dosages in relief of symptoms. Endoscopic assessment for the presence of erosion and hemorrhage after 1 and 2 weeks of famotidine treatment showed that the 10- and 20 mg doses were more effective in healing erosions and hemorrhages than was the 5 mg dose. After 2 weeks of treatment, 88.5% and 91.7% of the patients in the 10- and 20-mg dosage groups, respectively, did not have evidence of erosions or hemorrhages, compared with 73% of patients in the 5-mg group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889259 TI - Once-daily administration of famotidine for reflux esophagitis. AB - An open-labeled study of once-daily administration of 40 mg famotidine was conducted in 24 patients with endoscopically confirmed reflux esophagitis. The mean age of the patients was 62.8 years. Most had stage I or stage II esophagitis of 1 years' duration or less. After 4, 8, 12, and 16 weeks of treatment, endoscopically documented healing was reported in 50%, 75%, 82%, and 83% of patients, respectively. Among specific endoscopic findings documented at the start of the study there was clearing of white exudate in 83% of patients, and redness cleared in 50% of patients after 16 weeks of treatment. Symptomatic improvement was observed in 73% of patients after 2 weeks, and this increased to 81% and 85% after 4 and 8 weeks of treatment, respectively. Painful symptoms cleared within 2 weeks in 68% of patients, and this increased to 77% after 8 weeks of once-daily therapy. Famotidine was well tolerated. Historically, reflux esophagitis has not responded satisfactorily to drug treatment. The reported symptomatic response and the response documented by endoscopy after therapy with 40 mg famotidine once daily at bedtime are encouraging. Further studies should be conducted to define the role of famotidine in the treatment of reflux esophagitis. PMID- 2889260 TI - Famotidine: a notable lack of drug interactions. AB - Cimetidine, an H2-receptor antagonist, has been shown to inhibit the oxidative metabolism of several drugs by interacting with the hepatic cytochrome P450 system, which is involved in phase-I oxidative drug metabolism. Ranitidine, another H2-receptor antagonist, has been shown to have an extremely low level of interaction with the cytochrome P450 system. The potential of famotidine, a new H2-receptor antagonist with a guanylthiazole ring structure, to interact with the cytochrome P450 system has been extensively evaluated. Many of the studies used cimetidine and/or ranitidine as active controls. In vitro studies investigated the potential effects of famotidine coadministration on aminopyrine and diazepam demethylase activity, disturbances of P450 spectra, and effects on the metabolism of specific substrates such as deethylation of 7-ethoxycoumarin and demethylation of benzphetamine. Famotidine and ranitidine showed negligible interaction with the cytochrome P450 reactions studied, in contrast to the rather marked interaction demonstrated with cimetidine. Several in vivo animal studies investigated the effect of famotidine on hexobarbital sleeping time; plasma concentrations of diazepam, warfarin, and propranolol; antipyrine elimination kinetics; and warfarin prothrombin complex activity. Famotidine and ranitidine demonstrated either no evidence or minimal evidence of interaction with cytochrome P450 functions, in direct contrast to marked interactions produced by cimetidine. Human studies investigated the potential of an interaction with the coadministration of famotidine and aminopyrine, antipyrine, diazepam, theophylline, phenytoin, and warfarin. Coadministration of famotidine had no effect on the pharmacokinetic variables of theophylline, diazepam, desmethyldiazepam, and phenytoin and no effect on the half-life of antipyrine and aminopyrine or on the prothrombin time ratios associated with warfarin therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889261 TI - The morphological changes in the vestibular sensory epithelia following electrical stimulation. AB - The morphological changes of the vestibular sensory epithelia of the guinea pig following electrical stimulation were investigated using scanning electron microscope. Positive and negative square wave pulse stimulation was given through a silver ball electrode placed on the round window membrane for one hour. The current intensities used were 100, 200 and 300 microA. While the direct current stimulation at intensities of 100 or 200 microA did not cause any significant changes, severe damage of the utricular macula and the ampullar crista of the lateral semicircular canal was observed at 300 microA. The degenerative changes such as fusion of sensory hairs, protrusion of the cuticular plate and loss of sensory cells were found on both the utricle and the semicircular canal. In the most severely damaged area, the sensory epithelial surface was badly torn apart. In the clinical application of direct current to the inner ear for relieving tinnitus, special attention should be paid to the vestibular organ. PMID- 2889262 TI - Morphological changes in the vestibular epithelia and ganglion induced by ototoxic drug. AB - The morphological changes of the vestibular sensory epithelia and the vestibular ganglions induced by Gentamicin(GM) were investigated using scanning electron microscope, transmission electron microscope and light microscope. The guinea pigs were injected with a single application of 4 mg (0.1ml) of GM into the middle ear through the tympanic membrane. The vestibular organs and the ganglions were observed up to 6 months after the treatment. Four days after the injection, fused, ballooned and missing cilia were observed in the vestibular sensory epithelia. These changes progressed and extended toward the periphery of the crista and the macula. The changes of the vestibular ganglions were first observed one month after the treatment. The degenerative process started from destruction of the mitochondrial cristae and vacuolization of the cytoplasm in the Schwann cell. The next step of the change was dissociation of the myelin sheath around the ganglion cell. The cytoplasmic organelles in the ganglion cell gradually deteriorated. At the later stage, the myelin sheath around the ganglion cell disappeared and the number of the cell reduced. Furthermore, the myelin sheath of the nerve fiber was dissociated. In this study the signs of the vestibular ganglion damage were later than that of the vestibular organ. However, we thought the changes in the ganglion are probably due to direct influence of GM, since the degeneration was found to develop in a relatively short period. PMID- 2889263 TI - ["Chewing accidents", pre-existing conditions, late sequelae/recurrence, the Accident Insurance Law and private insurance]. PMID- 2889264 TI - [Regulation of immune responses by the autonomic nervous system and the endocrines]. PMID- 2889265 TI - [Is Dale's principle still valid?]. PMID- 2889266 TI - AIDS transmission and insects. PMID- 2889267 TI - Clonal analysis of human colorectal tumors. AB - The clonal composition of human colorectal tumors was studied by means of restriction fragment length polymorphisms (RFLPs). First, X-linked RFLPs were used to examine the pattern of X chromosome inactivation in colorectal tumors of females. All 50 tumors examined showed monoclonal patterns of X chromosome inactivation; these tumors included 20 carcinomas as well as 30 adenomas of either familial or spontaneous type. Second, RFLPs of autosomes were used as clonal markers to detect the somatic loss or gain of specific chromosomal sequences in colorectal tumors. Among other changes, it was found that somatic loss of chromosome 17p sequences occurred in over 75 percent of the carcinomas examined, but such loss was rare in adenomas. These data support a monoclonal origin for colorectal neoplasms, and suggest that a gene on the short arm of chromosome 17 may be associated with progression from the benign to the malignant state. PMID- 2889268 TI - [Changes of transplantation pecurialities of fetal liver hemopoietic stem cells after short-term culture in diffusion chamber in vivo]. PMID- 2889269 TI - Subdural empyema and epidural abscess: recent experience in a community hospital. AB - We treated 31 cases of localized central nervous system infection over a seven year period in our community hospital. The causes included brain abscess in 18 cases (58%); cranial subdural empyema (CSE) in six cases (20%); spinal epidural abscess (SEA) in four cases (13%); cranial epidural abscess (CEA) in two cases (6%); and spinal subdural empyema (SSE) in one case (3%). Both CSE and CEA were often caused by sinusitis and manifested by fever, headache, altered sensorium, and focal neurologic signs. Treatment consisted of drainage by burr holes or craniotomy followed by long-term administration of parenteral antibiotics. Though all patients with CSE and CEA survived, half had severe residual neurologic deficits. Both SEA and SSE were manifested by fever, spinal pain, and loss of motor function, and both were treated by laminectomy drainage and antibiotic administration. One patient died and three of the other four had residual neurologic deficits or back pain. Diagnosis of CSE and CEA was facilitated by CT scanning, while clinical examination, CT scanning, and myelography were useful in diagnosing SEA; SSE was not suspected preoperatively. PMID- 2889270 TI - Potential vectors of non-periodic form of Brugia malayi in East Kalimantan, Indonesia. PMID- 2889271 TI - The prevalence of Dirofilaria immitis in stray dog and its potential vector in Amphur Muang Chiang Mai, Northern Thailand. PMID- 2889272 TI - Physical and genetic localization of quinonoid dihydropteridine reductase gene (QDPR) on short arm of chromosome 4. AB - A portion of a cDNA clone corresponding to the 3' end of the human quinonoid dihydropteridine reductase (QDPR) mRNA was used as a probe to physically map the QDPR gene by analysis of somatic cell hybrid lines. The provisional assignment of QDPR to chromosome 4, based on expression of the human enzyme in hybrids, was confirmed. The gene was further regionally localized on the short arm to 4p16.1-- -4p15.1. This physical localization places QDPR in the same area of the genome that contains the defect causing Huntington's disease (HD). The QDPR probe revealed a restriction fragment length polymorphism with the enzyme BanII, permitting determination of its genetic proximity to D4S10, an anonymous DNA marker tightly linked to HD. QDPR is only loosely linked to D4S10, excluding any primary role for the gene in HD. PMID- 2889273 TI - Assignment of human tryptophan hydroxylase locus to chromosome 11: gene duplication and translocation in evolution of aromatic amino acid hydroxylases. AB - A cDNA clone for rabbit tryptophan hydroxylase was used as a probe to identify human tryptophan hydroxylase gene fragments in a panel of hamster-human somatic cell hybrids and determine its chromosomal location in man. A single locus was identified for tryptophan hydroxylase on chromosome 11. Tryptophan hydroxylase is a member of the superfamily of pterin-dependent aromatic amino acid hydroxylases which includes tyrosine hydroxylase, located at 11p15.5-p15, and phenylalanine hydroxylase, located at 12q22-q24.1 in human. The locations of these genes and the evolutionary distance between their sequences suggest that at least three distinct genetic events have occurred during the evolution of the aromatic amino acid hydroxylase superfamily: two sequential gene duplications giving rise to the three distinct hydroxylase loci, and a translocation which separated the tryptophan and tyrosine hydroxylase loci on chromosome 11 from the phenylalanine hydroxylase locus on chromosome 12. PMID- 2889274 TI - [Is the use of the mammary artery for the reconstruction of coronary arteries associated with a higher incidence of complications?]. PMID- 2889275 TI - [Sulfasalazine therapy in patients with rheumatoid arthritis]. PMID- 2889276 TI - Management of Henoch-Schonlein purpura and polyarteritis nodosa. PMID- 2889277 TI - Immunochemical characterization of the transglutaminase-catalyzed polymer of activated platelets. AB - Platelet proteins which contribute to transglutaminase-catalyzed polymer formation in activated platelets were identified by an immunochemical approach using the Western blot technique. The cross-linked polymer was purified from thrombin- or Ca2+-ionophore A23187-activated platelets by a sucrose density gradient procedure in reducing conditions and in the presence of a non-ionic detergent. Following transblotting of non-crosslinked platelet proteins from a Laemmli-type gel onto nitrocellulose, the platelet protein "lanes" were incubated with unabsorbed antibodies, or antibodies absorbed with purified polymer. Antibodies to native whole platelets as well as specific antibodies were used. The results show that myosin, actin, glycoproteins IIb, IIIa, and tubulin are present in the polymer. PMID- 2889278 TI - [Beta blockaders and anxiety--an alternative to benzodiazepines?]. PMID- 2889279 TI - [Acupuncture effective not only in China]. AB - The use of acupuncture in veterinary science is reviewed. The significance of this method under field conditions is discussed. Investigations on the mechanism of action and the effects of acupuncture are also discussed. Statistical studies showed that acupuncture may induce physiological and analgetic effects. PMID- 2889280 TI - Effects of thyrotropin releasing hormone (TRH) on glutamate-induced seizures in rats. AB - We investigated effects of TRH on glutamate-induced seizures in rats. Rats were injected intraperitoneally with sodium glutamate in a dose (22.3 mmole/kg) equivalent to ED95 for generalized convulsions. Twenty five min later TRH in a dose of maximum effect (40 micrograms in the tartrate form) was injected intracerebroventricularly in order that the time of peak effect was simultaneous with the onset of seizure which was anticipated from the preliminary study. TRH delayed the onset of initial seizures significantly, though neither occurrence nor incidence of various seizure activities was affected. A trend of delay in the mean time of death was also observed. These results suggest that TRH has an inhibitory action against glutamate-induced seizures in rats, albeit mild. PMID- 2889281 TI - A controlled trial of six-month and nine-month regimens of chemotherapy in patients undergoing radical surgery for tuberculosis of the spine in Hong Kong. Tenth report of the Medical Research Council Working Party on Tuberculosis of the Spine. AB - Sixty patients in Hong Kong with a diagnosis of tuberculosis of the thoracic, thoraco-lumbar or lumbar spine were allocated at random to either a 6-month (6M) or a 9-month (9M) regimen of daily isoniazid plus rifampicin, supplemented in all patients by streptomycin twice a week for the first 6 months. All patients had the modified 'Hong Kong' operation of radical resection of the lesion and insertion of autologous bone grafts. After exclusions, the main analyses of this report concern observations for 3 years on 51 patients (25 6M, 26 9M). The clinical and radiographic condition of the two series on admission was broadly similar. At 18 months, 19 of the 25 6M and 22 of the 26 9M patients had a favourable status, achieved on the allocated regimen that is, they had no clinical evidence of active disease, in particular no sinus or clinically evident abscess and no central nervous system lesions; they were capable of full physical activity and radiographically the lesion was quiescent. At 3 years, 24 patients in each series had a favourable status. Of the remaining three patients, one (9M) was clinically favourable but his spinal lesion was reported not yet quiescent at radiographic assessment. The other two patients (one in each series) had a favourable status in every respect except that they had required modifications of the allocated regimen; both had had a sinus at the site of the operation scar requiring surgical excision, with additional chemotherapy in one (9M). These modifications apart, all 25 6M and 25 of the 26 9M patients had a favourable status at three years. A sinus or clinically evident abscess was present on admission in seven patients (5 6M, 2 9M) and had resolved by 3 months in all seven, although one patient (6M) developed a sinus at the operation site subsequently. A further four patients (1 6M, 3 9M) developed an abscess or sinus for the first time after the start of treatment, but all resolved within 6 months. Two patients (one 6M, one 9M) had a mild paraparesis and one (9M) a cauda equina lesion on admission; all had resolved by 9 months. Radiographic evidence of bony fusion of the affected vertebral bodies had occurred in 36% of 25 6M and 42% of 26 9M patients at 6 months, in 44% and 77% respectively at 9 months (P = 0.03), 68% and 88% respectively at 18 months and 100% in both series at 36 months.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2889283 TI - Elastic fibers in tunica propria of undescended and contralateral scrotal testes from cryptorchid patients. AB - Elastic fibers in the tunica propria of the testes from cryptorchid patients and normal fertile adults were examined by light (Weigert resorcin-fuchsin stain) and electron microscopic techniques. In the testes from normal fertile adults, elastic fibers were proved to exist in the tunica propria by light and electron microscopy, and were located in the fibrous and cellular layers of the tunica propria. In the undescended testes from the cryptorchid patients, during prepubertal and pubertal periods, elastic fibers could not be visualized in the tunica propria, but were found after puberty. The positive Weigert reaction of the tunica propria in the undescended testes from postpubertal cryptorchid patients, however, was markedly weaker than that in normal control patients, suggesting diminution of elastic fibers. This diminution of elastic fibers in the undescended testes from postpubertal cryptorchid patients was also substantiated by electron microscopy. However, in the contralateral scrotal testes, elastic fibers appeared during puberty and were observed after puberty in the same manner as in normal testes. Thus, the present study suggested retarded appearance of elastic fibers in puberty and impaired development of those fibers after puberty, in the undescended testes of cryptorchid patients. PMID- 2889282 TI - Optimal discrimination of mild hyperparathyroidism with total serum calcium, ionized calcium and parathyroid hormone measurements. AB - The serum concentrations of calcium, albumin and parathyroid hormone (PTH) and the plasma levels of ionized calcium were determined in 124 healthy subjects, 89 patients with primary hyperparathyroidism (HPT), 23 of whom had the syndrome of multiple endocrine neoplasia type 1 (MEN-1) and 43 patients who had hypercalcaemia of other causes than HPT (non-HPT), in most cases due to widespread malignancies. The total serum calcium was corrected for the serum albumin concentration (CaM). Healthy females over the age of 50 had higher CaM, than younger females and the women of all ages also had, higher serum PTH levels than males. For all study groups both the intra- and inter-diurnal variations were small for all the studied variables. Discriminant function and optimal discriminatory limits were calculated with the help of computer programs. A consideration of all the individuals in the discriminant analysis, revealed that measurements of CaM alone separated most HPT patients both from the healthy subjects and from the non-HPT patients. However, when only those who had borderline values (defined as CaM between 2.45 and 2.75 mmol/l) were included it turned out that measurements of ionized calcium markedly improved the delineation of mild HPT from the healthy subjects and that, in addition, PTH measurements helped to exclude those with non-HPT hypercalcaemia. The optimal discriminatory levels of serum calcium were calculated as the levels which caused the minimum loss in terms of misclassification when attention was paid to the relative importance of false positive to false negative classifications and to the prevalence of HPT. The optimal discriminatory level for serum calcium for a weighting ratio between false positive to false negative of 1:1, and a prevalence of HPT of 1%, was calculated to be 2.68 mmol/l and for a prevalence of 50% 2.56 mmol/l. In the latter situation a weighting ratio of 10:1 for false positive to false negative gave a level of 2.63 mmol/l while a weighting ratio of 1:10 corresponded to an optimal discriminatory level of 2.47 mmol/l. PMID- 2889284 TI - Influence of idazoxan on the respiratory blood gas changes induced by alpha 2 adrenoceptor agonist drugs in conscious sheep. AB - Administration of either xylazine (50 micrograms/kg) or detomidine (10 micrograms/kg) caused a significant degree of arterial hypoxaemia in six conscious sheep. This effect was independent of any changes produced by changes in posture as all the sheep remained standing. Administration of the specific alpha 2-antagonist drug idazoxan (0.1 mg/kg bodyweight) five minutes before injection of either of the drugs completely abolished the hypoxaemia. These results lend support to the view that the respiratory effect of these drugs is mediated via alpha 2-adrenoceptor activity. PMID- 2889285 TI - Epizootic of Rift Valley fever in Zambia, 1985. PMID- 2889286 TI - Occurrence and properties of FY(Att25)+ Escherichia coli associated with diarrhoea in calves. AB - Escherichia coli producing the adhesive antigen FY(Att25) were isolated from 46 of 1341 (3.4 per cent) E coli isolated from calves on 20 of 164 (12.1 per cent) farms in Scotland and England. Twenty of the 46 calves had diarrhoea and in nine of these animals there were mixed infections with rotavirus, coronavirus, cryptosporidium and Salmonella typhimurium. The F41 fimbrial adhesin was found on one of the FY(Att25)+ E coli. This strain also produced heat stable enterotoxin. The remaining FY(Att25)+ isolates did not produce other adhesins, enterotoxins or verotoxins. The FY(Att25) antigen was not detected on 109 pathogenic E coli isolated from calves, chickens, lambs, pigs or man. PMID- 2889287 TI - British congress for IVSA. PMID- 2889288 TI - Comparison of surface hydrophobicity of piliated and non-piliated clones of Corynebacterium renale and Corynebacterium pilosum. AB - Piliated (P+) and non-piliated (P-) clones of Corynebacterium renale and C. pilosum were similar in hydrophobicity as measured by hydrophobic interaction chromatography, bacterial adherence to hydrocarbons and the salt aggregation test. Therefore, the previously reported adherence of P+ clone to various cells, which is more effective than that of P- clone, may be uncorrelated with the degree of hydrophobicity of both clones of these bacteria. Hydrophobicity of P+ and P- clones was found to be high when measured by hydrophobic interaction chromatography and bacterial adherence to hydrocarbons, but low when measured by the salt aggregation test. PMID- 2889289 TI - Hepatotoxicity of immunotoxins made with saporin, a ribosome-inactivating protein from Saponaria officinalis. AB - Immunotoxins were prepared by conjugating saporin, a ribosome-inactivating protein from Saponaria officinalis, to a monoclonal antibody against the Thy1.1 antigen, or to its F(ab')2 fragment. The immunotoxins were eight- to 16-fold more toxic to mice than free saporin. Injection of the immunotoxins induced necrosis of the liver and spleen, whereas free saporin caused necrosis of the epithelium of the kidney tubules. The cytoplasm of the hepatic parenchymal cells was affected by the immunotoxins, lesions being apparent in the rough endoplasmic reticulum and, later, in the mitochondria. These changes were associated with a reduced capacity to synthesise proteins both in the intact liver and by isolated liver microsomes. Studies of the in vivo distribution showed that 90% of the free saporin was removed from the bloodstream, mainly by the kidneys, within 10 min of injection. By contrast, the immunotoxins persisted in the blood for several hours and the only organ in which they consistently accumulated was the liver. The hepatotoxic effect of the immunotoxins was not due to their binding to liver cells via the antigen-binding sites or the Fc-piece of the antibody moiety, nor was it due to hepatic recognition of carbohydrate in the immunotoxin. It is concluded that free saporin, although capable of entering liver cells, is filtered so rapidly by the kidney that liver damage does not occur to a significant extent. Filtered saporin, however, is reabsorbed by renal tubules, whose epithelial cells are damaged. The antibody-saporin conjugate is too large to filter at the glomerulus and so has greater opportunity to penetrate into and to damage the hepatic parenchymal cell. PMID- 2889290 TI - Altered enzyme expression in propylnitrosamine-induced Syrian hamster lung lesions. AB - Focal proliferative and neoplastic lung lesions induced in Syrian hamsters by dihydroxy-di-n-propylnitrosamine (DHPN) were investigated using a combined histochemical, autoradiographic and electron microscopic approach. Expression of elevated glucose-6-phosphate dehydrogenase (G6PD) and gammaglutamyl transpeptidase (GGT) activities and levels of immunohistochemically demonstrable glutathione S-transferase placental form (GST-P) were evident in epithelial cells of focal proliferative populations and bronchioloalveolar neoplasms. Binding for the GST-C form, normally only weak, became very pronounced in the stromal elements of DHPN-induced lesions. Increased labelling with tritiated thymidine was associated with increase in morphological atypia within the tumours. Although the enzyme phenotype findings were equivocal the presence of lamellar bodies in some cells of focal proliferative and neoplastic lesions suggested an origin from alveolar type II cells. The present results regarding changed enzyme phenotype in lung lesions suggest important similarities at the biochemical level for the process of neoplasia in the different target organs of DHPN in the hamster and indicate that GST-P may be a useful 'marker' for lung neoplasia. PMID- 2889291 TI - Epidermal cell proliferation. I. Changes with time in the proportion of isolated, paired and clustered labelled cells in sheets of murine epidermis. AB - A new technical approach to analysing labelled cells in sheets of epidermis is presented. The changes in the proportion of isolated single labelled cells, paired or clusters of 3, 4, or more than 4, labelled cells in sheets of epidermis from the back of the mouse have been analysed at various times up to 500 h after 3HTdR administration at either 03.00 h or 15.00 h. The technique is not dependent on the relative number of labelled cells (i.e. the labelling index) but on the spatial distribution of labelled cells. The data cannot be adequately explained on the basis of a simple homogeneous stem cell population in the basal layer but can be better understood on the basis of an hierarchical stem cell-dividing transit proliferative model. The data are consistent with an average cell cycle time of about 100 h but there are suggestions of considerable cell kinetic heterogeneity. The data also suggest that the amount of lateral cell movement within the basal layer is small. The results may suggest that some stem cells either loose label in a manner similar to that suggested by Cairns (1975) i.e. through a process of selective segregation of their DNA strands, or that they have an extremely short S phase duration as postulated earlier (Potten et al. 1982). The present data have been extensively mathematically modelled in an accompanying paper. The model which best fits all the data is an hierarchical scheme with three cell divisions in the transit population but some branches of the lineage may be prematurely terminated by the early production of post-mitotic cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889292 TI - Epidermal cell proliferation. II. A comprehensive mathematical model of cell proliferation and migration in the basal layer predicts some unusual properties of epidermal stem cells. AB - The clustering of 3HTdR labelled cells in the epidermal basal layer and their changes with time have been modelled mathematically and cannot be adequately fitted by an earlier model of the cell kinetic organisation of the skin. A more refined model analysis was performed based on Monte Carlo computer simulations of cell layers which take cell division, cell aging and lateral as well as vertical cell migration into account. A large variety of hypothetical scenarios was tested to see if each could provide a fit to the clustering data. The analysis provides further support for the concept of a cell kinetic heterogeneity with a stem transit-postmitotic differentiation scheme. In the best overall model scheme three transit divisions are predicted but unlike in the earlier model it is now postulated that postmitotic cells can be produced at all stages in the lineage rather than only at the end of the amplification scheme. Most important, the model predicts that stem cells and most of the transit cells differ in the way they process 3HTdR label. Grain dilution is an important mechanism to explain the fate of some labelled cells in the tissue, but on its own it can only consistently explain the data if the stem cells have a very low labelling index (LI less than or equal to 1%) which implies a very short biologically unreasonable S-phase. If a higher LI (longer S-phase) is assumed for the stem cells other mechanisms must be predicted to explain the lack of large clusters and the increase in time of the singles. The selective segregation of chromosomes at mitosis is one such mechanism. However, on its own a large number of cells would have to behave in this way (i.e. both stem and T1 cells). If combined with other assumptions such as some grain dilution this selective segregation may be restricted only to stem cells. In addition the model allows cell production and migration rates to be estimated and the analysis can be related to the EPU concept. Indeed the model itself would tend to automatically generate an EPU like structure. The model quantitatively reproduces LI, PLM, CL and clustering data. PMID- 2889294 TI - Distribution of growth hormone and prolactin in secretory granules of the normal and neoplastic human adenohypophysis. AB - Growth hormone [GH] and prolactin [PRL] can be demonstrated simultaneously in electron micrographs by means of the double immunocytochemical labeling technique using colloidal gold particles of two different sizes. This method was used to study biopsy specimens obtained from 15 patients suffering from acromegaly, 11 patients suffering from prolactinomas, and eight biopsy specimens obtained during adenomectomy from the normal, paraadenomatous pituitary tissue. Four granule populations with different immunoreactions were found: (1) granules containing GH only, (2) granules containing PRL only, (3) mixed granules containing GH and PRL, and (4) granules displaying no immunoreactivity. The existence of mixed granules indicated that the two hormones are synthesized by the same cell and in communicating compartments of the cells; i.e., the rough-surfaced endoplasmic reticulum. The number of GH-containing granules (pure GH granules and mixed GH PRL granules) was greater than that of PRL-containing granules (pure PRL granules and mixed PRL-GH granules) in adenomas causing acromegaly and in the normal pituitary tissue, whereas the opposite was true for prolactinomas. The number of PRL-containing granules was larger in biopsy specimens from patients who had acromegaly and hyperprolactinemia than in patients with acromegaly and normal serum PRL levels. PMID- 2889293 TI - S-100-positive T cells are largely restricted to a CD8-positive, 9.3-negative subset. AB - The present report concerns the demonstration of the exclusive detection among peripheral blood T-lymphocytes of the S-100 protein within the CD8-positive subpopulation which lacks the antigen recognized by the 9.3 monoclonal antibody. Highly purified human peripheral blood T-cell subsets, obtained by means of panning techniques, were first stained, by an immunofluorescence method, with purified anti-S-100 protein antibodies. The vast majority of S-100 protein- (and, specifically, its beta subunit) positive cells were detected in the CD8-positive, 9.3-negative subset. This subset had previously been shown to comprise all the alloantigen-specific and histamine-inducible suppressor T-cells. Other T-subsets, even those showing either CD8-positivity (but 9.3-positivity) or 9.3-negativity (but CD8-negativity), were, as a rule, S-100 negative. Immunoelectronmicroscopy confirmed that the S-100-positive cells, showing peroxidase activity within the cytoplasm, were found exclusively within the CD8-positive, 9.3-negative subset. This finding of S-100 protein in cells of a specific T8 suppressor subset extends the range of the known distribution of this protein and may have important implications concerning its role in the modulation of immune responses. PMID- 2889295 TI - Quantitative histology of muramyl dipeptide-potentiated induction of tumor necrosis by endotoxins. AB - Combinations of muramyl dipeptide (MDP) and toxic or detoxified endotoxin induced necrosis and subsequent disappearance of solid Meth A tumors in syngeneic mice. Toxic endotoxin alone was far less effective. MDP and detoxified endotoxin had negligible antitumor effects of their own. These observations were confirmed by histological examination. Neither MDP nor detoxified endotoxin induced significant changes in and around the tumor by 4, 24, and 48 h after intravenous administration when compared with saline treatment. MDP amplified various effects of toxic endotoxin such as the induction of hyperemia, mitotic arrest, mast cell depletion, non-hemorrhagic necrosis and reduction in lymphocyte infiltrates, but did not affect hemorrhagic necrosis or the influx of polymorphonuclear leukocytes. The combination of MDP and detoxified endotoxin lacked the latter two effects, but the other effects were similar to, although slightly less marked than those induced by the toxic combination. Because the degree of hyperemia was proportional to the degree of subsequent non-hemorrhagic necrosis, MDP seems to potentiate necrosis by enhancing mechanisms leading to hyperemia and mast cell mediators might be involved in the latter effect. Lymphocyte influx and the therapeutic outcome are likely to be related, since exclusively therapeutic treatments reduced the influx of these cells. PMID- 2889296 TI - [A simple and sensitive modification of the fluorimetric method for determining tyrosine hydroxylase activity in brain tissue]. AB - A simple and sensitive modification of fluorimetric method for determination of tyrosine hydroxylase activity in the small samples of brain tissue is described. PMID- 2889297 TI - Arthropod-borne viruses isolated in Czechoslovakia. PMID- 2889298 TI - [H2 receptor antagonists in the therapy of peptic ulcer disease]. AB - Today histamine-H2-receptor antagonists are the most intensively investigated drugs in the therapy of acid related diseases. They are characterized by a clear mechanism of action, a convenient application form, a high tolerability, a low incidence of side effects, and a large therapeutic window. The single nocturnal dosage regimen of H2-blockers follows the concept to reduce substantially night time acidity only, which is believed to play a decisive pathogenetic role in peptic ulcer disease, while during day time physiological acid secretion remains unaffected. The clinical efficacy of this application form has been well documented in the healing and symptomatic relief of acute peptic ulcers. However, about 30% of patients still suffer from ulcer pain after a 2 weeks treatment period. A more flexible dosage regimen, which is more adapted to the ulcer symptoms of the patient will probably lead to even better clinical results. PMID- 2889299 TI - [Omeprazole in the therapy of acid-induced diseases]. AB - Omeprazole is a substituted benzimidazole which inhibits profoundly and long lasting human acid secretion. The maximum inhibition effect of omeprazole begins after 3-5 days treatment. Even after 28 days application no significant rebound effects were seen after withdrawal from the medication. Omeprazole was clinically tested on several thousand patients. The daily doses of 20 mg to 60 mg in cases of duodenal ulcer led to healing rates of 60-100% after 14 days. In direct comparative studies omeprazole was superior in cases of duodenal ulcers to cimetidine and ranitidine. With regard to gastric ulcers identical successful results were seen with 20 mg omeprazole daily as with 2 X 150 mg ranitidine daily. Omeprazole was also superior to H2-blockers in the treatment of erosive reflux-oesophagitis. Results from long-term therapy with the exception of Zollinger-Ellison syndrome are not yet available. In the clinical studies, omeprazole proved to be well tolerated. Its definite place in the management of peptic ulcer disease, however, remains to clearly established. PMID- 2889300 TI - [Somatostatin and opioids, secretin and VIP--protectors of the mucosa?]. AB - Somatostatin is located predominantly in D-cells of the antral and fundic area of the stomach and in the duodenal bulb. Furthermore, somatostatin is contained in neurons of the extrinsic and intrinsic nervous system. Somatostatin inhibits gastric acid, pepsin and gastrin secretion, and it stimulates gastric mucous secretion. All in all, somatostatin could exert protection of the gastric mucosa by reduction of aggressive and augmentation of protective mechanisms. There is, however, no evidence for a role of somatostatin in the pathogenesis of peptic ulcer. Endogenous opioids which have to be considered as potential peptidergic neurotransmitters increase vagal and postprandial gastric acid secretion and accordingly cannot be considered as a protective factor. Vasoactive intestinal peptide (VIP), also a peptidergic neurotransmitter, reduces acid and stimulates mucous and bicarbonate secretion. If this is of physiological relevance remains to be established. Secretin might be a protective factor for the gastric mucosa by stimulating mucous and bicarbonate secretion. On the other hand, it augments pepsin secretion which might attenuate any potential protective effects of secretin. PMID- 2889301 TI - [Screening of benzo- and thienodiazepines in urine with Emit ST and thin-layer chromatography within the scope of substance abuse]. AB - All 24 Benzo- and Thienodiazepines which are used in drugs in the FRG were added to drug free urine in different concentrations and examined by Emit ST as well as by TLC. In addition the acid hydrolysis products of diazepines were analysed by TLC. A modification of the extraction procedure is described, which shortens analysis time considerably. The detection limits were determined and it will be discussed how both methods, Emit and TLC, are suited for a wide-ranging drug screening program. PMID- 2889302 TI - States causing infertility in adulthood in children with undescended testis. AB - A total of 1386 operations for undescended testis was made in 1250 boys. In 774 of them an apparently intact testis and epididymis were found. In 612, such epididymal developmental abnormalities were detected which exclude or do not make possible the passage of sperms from these organs to the deferent duct. It is believed to be plausible that the large number of cases with infertility is due, also in individuals with a unilateral cryptorchidism, to the abnormal fusion of the epididymis in both testes. PMID- 2889304 TI - Perforation and necrosis of the colon complicating polyarteritis nodosa. Case report. AB - Polyarteritis nodosa in a 23-year-old man gave rise to caecal perforation, colonic infarction and, later, severe gastrointestinal bleeding with fatal outcome. The necessity of early surgical intervention to improve prognosis in cases with severe gastrointestinal improvement is emphasized. PMID- 2889303 TI - Effects of betaxolol on heart rate in patients with a recent transmural myocardial infarction. AB - A randomized double-blind trial was performed with betaxolol, a beta 1-selective and long-acting beta-blocker, in patients with a recent first uncomplicated acute myocardial infarction (AMI). Patients were treated between the 3rd and 14th day after the onset of AMI with either a single oral dosage of 20 mg betaxolol or placebo. The effects on heart rate, ventricular and supraventricular arrhythmias were studied by continuous 24 hours ECG recordings on the 7th and between the 9th to 12th after the onset of AMI and by a submaximal exercise test on the 12th day. Hourly mean, peak and minimal heart rate were during the whole day significantly lower in the active treatment group. In betaxolol treated patients diurnal variations in heart rate were definitely changed. No differences in the occurrence of ventricular arrhythmias were found between both groups; auricular fibrillation was more common in placebo treated patients. Heart rate and pressure rate product were significantly higher during exercise in the placebo group. During exercise ventricular arrhythmias were infrequent in both groups. The clinical tolerance of betaxolol was excellent. PMID- 2889305 TI - [Digital necrosis: a paraneoplastic syndrome]. PMID- 2889306 TI - The effect of subcutaneous infusion versus subcutaneous injections of a somatostatin analogue (SMS 201-995) on the diurnal GH profile in acromegaly. AB - Multiple sc injections of a long-acting somatostatin analogue (SMS 201-995) are currently used in the treatment of acromegaly. However, plasma GH concentration often reaches a pathological level (less than 5 micrograms/l) between two injections. In seven patients with active acromegaly we compared, in a short-term trial, the effect of SMS 201-995 administered by continuous sc infusion (50 micrograms and 100 micrograms a day) and by three sc injections (100 micrograms each). In six patients, plasma GH levels were significantly reduced regardless of the mode and dose of treatment (P less than 0.05). However, comparing diurnal profiles, 100 micrograms continuous sc infusion was more effective than discontinuous administration in reducing the number of GH levels above 5 micrograms/l (P less than 0.01). In two patients, continuous infusion was the only way to decrease all plasma GH values below 5 micrograms/l during the diurnal profile determination. Moreover, even when, in a long-term study, the dose of multiple injections was progressively increased to 500 micrograms three times a day, GH levels remained consistently elevated in one of these patients. Thus, in some acromegalic patients continuous sc injection seems currently the most efficient way of treatment with SMS 201-995. PMID- 2889307 TI - Plasma growth hormone in acromegalic patients. Demonstration of highly reproducible diurnal profiles in individual patients. AB - The effects of the selective alpha 2-adrenoreceptor antagonist idazoxan on diurnal variations in plasma growth hormone levels were studied in acromegalic patients. Seven patients entered the study; six patients had been unsuccessfully treated with either pituitary adenotomy, bromocriptine or other drug therapy or a combination of the two procedures. Plasma growth hormone levels were measured at hourly intervals over a period of 24 h under control conditions and following 4 days treatment with either placebo or idazoxan (20 mg po, three times a day); the comparison of idazoxan with placebo was a double blind cross-over study. Except in one patient, the diurnal growth hormone plasma profiles were virtually superimposable under control conditions and following either placebo or idazoxan; each patient had a characteristic profile. Four patients had impressive nocturnal elevations ranging from about 40 to 200 per cent above average daytime levels. Only one had definite paradoxical early postprandial peaks. These observations are contrary to accepted views on growth hormone levels in acromegalic patients. The majority of our patients thus had profiles reminiscent of the normal diurnal plasma growth hormone pattern albeit at a higher level indicating some preserved central drive. The rather high prevalence in the present study of patients having relapses after adenomectomy may indicate that a selection had been made of cases with hypothalamic aetiology. Administration of the selective alpha 2 adrenoreceptor antagonist idazoxan did not modify plasma growth hormone profiles in these patients. PMID- 2889308 TI - Growth hormone responses to the releasing hormones GHRH and GnRH and the inhibitors somatostatin and bromocriptine in TRH-responsive and non-responsive acromegalics. AB - In acromegalics, the percent peak GH responses to TRH (pTRH) and bromocriptine (pBr) are inversely related with those to GHRH, favouring the hypothesis that in the adenomas of some patients there is a preponderance of GH-producing cells with lactotrope-like characteristics, whereas in others pure somatotropes predominate. The aim of the present study was to investigate whether patients responsive to TRH with allegedly lactotrope-like tumours differ from those patients not responding to TRH with more somatotrope-like adenomas in their answer to the GH inhibitors Br and SRIH and the releasing hormones GHRH and GnRH. The present study demonstrates that the observed reciprocal relations between the GH responses to GHRH, TRH and Br are only present in acromegalics paradoxically responding to TRH (pGHRH vs pTRH -0.73, pGHRH vs pBr -0.60, pTRH vs pBr +0.54, P less than 0.0002-P less than 0.02, N = 20), not in TRH-non-responders (N = 10). In contrast, in these latter patients, not in the former, close relations were found between the percent peak GH responses to GnRH (pGnRH) and pGHRH (r = +0.81, P less than 0.005) and between pGnRH and the percent maximum GH decrements in response to SRIH (pSRIH) (r = +0.64, P less than 0.05). Expectedly, the GH response to Br in the TRH-responders was significantly higher than in the non responders (75 +/- 4% vs 54 +/- 3%, P less than 0.02), although it was also substantial in the latter. The GH response to SRIH was remarkedly similar in both groups (64 +/- 5 vs 57 +/- 9%, P greater than 0.10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889309 TI - Thyroid stimulating antibody: an index of thyroid stimulation in Graves' disease? AB - Early (20 min) thyroid radio-iodine uptake (ERU) and thyroid-stimulating antibodies (TSab) were determined in 27 untreated unselected patients with Graves' disease at the time of diagnosis. In 21 subjects the same tests were further performed in parallel during combined carbimazole-L-T3 therapy (mean duration of follow-up: 10.8 +/- 5.8 months; mean +/- SD). TSab was determined by a cAMP-human thyrocyte culture stimulation assay and expressed in microliter equivalent of a TSab standard/ml (microliter-eq/ml). Before treatment, ERU, ranging from 15 to 54% of the injected dose (normal less than or equal to 8% dose) correlated with serum T3 (r: 0.54; P less than 0.01); TSab, ranging from 6 to 85 microliter-eq/ml was detected in 21/27 patients. There was a significant correlation between ERU and TSab (Spearman rank test: r: 0.57; P less than 0.01). During the first months of treatment, 5 of the 21 patients sequentially studied had undetectable TSab levels throughout the study and in these patients ERU decreased by 57% of its initial value; the remaining 16 subjects were divided into two groups according to ERU changes: in group A (9 patients), initial ERU decreased by 50% or more or the absolute value became less than 20% of the dose and TSab decreased from 10.9 +/- 4.8 microliter-eq/ml to 5.3 +/- 1.6 microliter eq/ml (P less than 0.01); in group B (7 patients), the fall of ERU was less than 50% or the absolute value remained greater than 20% of the dose and TSab values remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889310 TI - The role of opiate, dopaminergic, and adrenergic systems in the hypothalamo pituitary dysfunction in obesity. AB - In order to evaluate the role of opiate, dopaminergic and adrenergic systems in the mechanism of hypothalamo-pituitary disturbances in obesity, 9 obese women and 14 healthy women were investigated. Serum GH, LH, beta-endorphin and cortisol concentrations were measured after administration of clonidine, an alpha 2 adrenergic receptor agonist, and naloxone, an opiate antagonist. Additionally, PRL levels were measured after administration of the dopamine receptor blocker metoclopramide. An impaired GH response to clonidine and naloxone was found in obese women. However, a marked increase in beta-endorphin was observed in obese patients after clonidine administration. Naloxone did not cause any significant change in beta-endorphin release. Neither clonidine nor naloxone induced any change in LH release. Serum PRL concentrations in response to metoclopramide were significantly higher in obese patients than in healthy women. IN CONCLUSION: Disturbed activity in opiate, adrenergic, and dopaminergic systems may be of pathogenetic importance in a hypothalamo-pituitary dysfunction in obesity. The occurrence of hypothalamic amenorrhoea as well as the presence of abnormalities of the central nervous system regulation of GH, PRL, ACTH, cortisol, insulin and vasopressin output might point to a generalized hypothalamo-pituitary dysfunction in obesity. PMID- 2889311 TI - Clinical outcome of HIV infection. PMID- 2889312 TI - Pain therapy: from theoretical research to clinical application. AB - After a brief review of the supraspinal and spinal effects of morphine, the reference substance for studies on analgesia, the authors expose a synthesis of the recent literature regarding neurotransmitter involvement in pain perception and transmission. From these data, some future prospects for pain treatment research are identified. PMID- 2889313 TI - Cryoanalgesia for post-thoracotomy pain relief. AB - A randomized study comparing the postoperative requirements of narcotics of three groups of patients (Group I: no analgesia; Group II: internal intercostal nerve block; Group III: cryoanalgesia) was conducted. This study was performed in order to assess the efficiency of cryoanalgesia versus internal intercostal nerve block to obtain pain relief after thoracotomy. Regarding post-operative narcotic requirements (Piritramide-Dipidolor), there was no significant difference between Group I and Group II patients, but patients from Group III required a significantly lower amount of narcotics during the first 36 postoperative hours (p less than 0.01). We conclude that, although cryoanalgesia does not provide complete post-thoracotomy pain relief, it is however an easy and safe method and is more efficient than internal intercostal nerve block for pain relief after thoracotomy. PMID- 2889315 TI - Recent advances in the inherited methylmalonic acidemias. AB - Methylmalonic acidemia results from decreased activity of methylalonyl-CoA mutase, an enzyme required for the catabolism of four amino acids. A cobalamin (vitamin B12) compound is required as coenzyme. Several inherited mutations of the mutase apoenzyme or of cobalamin coenzyme synthesis have been identified. Clinical disease is most commonly recognized as a severe protein intolerance state although a wide range of symptoms has been appreciated. Current therapy emphasizes strict dietary management and use of vitamin B12 in cobalamin responsive patients. PMID- 2889314 TI - The effect of labetalol on contractility of human myometrial preparations. AB - Because of results in animal experiments which demonstrated a partial beta 2 adrenoceptor activity of labetalol on rat uterine smooth muscle the present study was conducted in human preparations. The following results were obtained: 1. Rhythmic uterine contractions with a defined steady-state amplitude and frequency were elicited spontaneously and after methylergometrine. 2. Labetalol reduced amplitude of contractions dose-dependently after 3 h of incubation. Frequency was unaffected. 3. The tocolytic effect of labetalol is apparent only at high concentrations, above those used in the treatment of hypertension. 4. Neither beta 2-specific adrenoceptor blockade with ICI 118,551 nor alpha-blockade with phentolamine changed amplitude of contraction, either alone or in combination with labetalol. 5. Labetalol has little tocolytic effect on human myometrium in vitro. This effect is unrelated to alpha- or beta-antagonism, but seems to depend on a direct smooth muscle depressant effect. In conclusion, from the present in vitro experiments using human myometrial preparations, it seems unlikely that labetalol would interfere with the normal process of labor when used for the treatment of pregnancy hypertension. PMID- 2889317 TI - Fecal colonization with P-fimbriated Escherichia coli in newborn children and relation to development of extraintestinal E. coli infections. AB - The incidence of E. coli pyelonephritis before the age of one year among the children born at Danderyd Hospital during a ten year period was studied. During the study period, 4 or 5 outbreaks of E. coli pyelonephritis occurred among the children who had previously been staying in the hospital's neonatal ward. These outbreaks seemed to have been caused by nosocomial spread of and fecal colonization with certain virulent E. coli strains among the children staying in the ward during certain periods of time. The strains that were spread in the ward seemed to belong to certain pyelonephritogenic E. coli clones of the serotypes O6:K5, O4:K3 and possibly O6:K2. Although the children became fecally colonized with the strains in the neonatal ward, most fell ill some time after they had left the ward. The mean age at the development of their first pyelonephritis was 3.4 months for the boys and 6.2 months for the girls, who had been cared for in this ward. A correlation between the number of infections and the bed occupancy of the ward could be found (p less than 0.01). The risk for a child staying in the ward during an outbreak to develop pyelonephritis was about 5-10%. There was a baseline incidence rate of 0.6-0.7% during non-epidemic periods. During one of the outbreaks there was also an increased incidence rate of E. coli septicemia among the children staying in the neonatal ward. The predictive value of fecal colonization with P-fimbriated E. coli for the later development of extraintestinal E. coli infections was studied in a 2.5 year prospective study. During this study period there was a baseline incidence rate of 10-20% fecal colonization with P-fimbriated E. coli among the children staying in both the neonatal and maternity wards, interrupted only by minor peaks of colonization with such strains. Length of stay in the neonatal ward and a high bed occupancy of the neonatal ward were statistically correlated to fecal colonization with P fimbriated E. coli strains (p less than 0.01). During the prospective study there was no difference in the incidence rates of pyelonephritis before the age of one year between the neonatal and maternity ward children. These incidence rates were 0.59% and 0.66%, respectively. Only one of the 113 children from the neonatal ward who were fecally colonized with P-fimbriated E. coli strains later developed pyelonephritis. Thus, there was no predictive value of fecal colonization with P fimbriated strains for the later development of pyelonephritis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2889316 TI - P-fimbriated Escherichia coli in children with acute cystitis. AB - P-fimbriation of Escherichia coli is an important factor in the pathogenesis of childhood pyelonephritis. The present study investigates children with single episodes of symptomatic non-febrile urinary tract infection, i.e. cystitis, with respect to clinical appearance and bacteriology, especially the frequency of P fimbriated E. coli. The study included 75 children, 57 of whom had their first attack of urinary tract infection. E. coli was the causative agent in 88% (66/75) of the infections, and 48% (32/66) of E. coli strains were P-fimbriated. No association was found between identification of P-fimbriated E. coli at index infection and proneness to reinfection during the following six-month period. It is suggested that P-fimbriated E. coli is a virulence factor even in lower urinary tract infections, when occurring in single, symptomatic episodes. PMID- 2889318 TI - [Effects of exciting the habenula by L-glutamic acid on the pain threshold and acupuncture analgesia]. PMID- 2889319 TI - Effects of ginsenosides on sympathetic neurotransmitter release in pithed rats. PMID- 2889320 TI - [Erythema multiforme, ulcerative colitis and salazopyrine]. PMID- 2889322 TI - [Controlled arched osteotomy for the correction of malposition in healed fractures]. AB - The guided arched osteotomy and the oscillating saws specially developed for this operation have proven to be a competent technique to correct malposition following fractures. Its essential advantage is that the equipment offers the possibility to perform an exact and protective cylindrical cut, which assures exact parallel, relatively large contact areas and hence a favourable postulate for the healing action. Moreover, the saddle-shaped contact area offers protection against unwanted rotation. Furthermore, the shortening of the bone is limited to the width of the very thin saw cut performed. An additional advantage is offered in the possibility to carry out further correction without the necessity of a repeated osteotomy, should the x-ray control show that the primary correction has not turned out satisfactorily. PMID- 2889323 TI - [Early functional treatment of humerus shaft fractures by the Sarmiento method]. AB - The functional treatment of humerus shaft fractures with a brace according to Sarmiento is described. Reported are the results of the functional treatment of 47 humerus shaft fractures. Every humerus shaft fracture normally treated conservatively, including the humerus shaft fractures in polytraumatised patients and those patients with a primary radial nerve injury, can be treated in this way. The functional treatment of humerus shaft fractures results in a quick and uneventful healing of the fracture with a good function and cosmetic aspect. PMID- 2889321 TI - Fibre and the diabetic diet. An evaluation of the metabolic response to standardized meals. AB - Dietary fibre has a beneficial influence on glucose homeostasis, varying for different fibre sources. Fruit, wheat, rye and beet fibre were studied in isoenergetic meals for NIDD patients and healthy volunteers. The effects of extrusion cooking and flaking were also evaluated. The metabolic response was followed by continuous glucose monitoring and by analyses of pancreatic and gastrointestinal hormones as well as plasma lipid concentrations, For NIDD patients the effects, reflected in the area and the shape of the glucose curve, were greater for the more soluble fibre types, but the insulin and C-peptide responses were largely unaffected by dietary fibre. Beet fibre gave increased somatostatin concentrations also in age-matched healthy controls. They showed, however, unchanged plasma glucose responses and markedly decreased insulin and C peptide levels. These changes were associated with less pronounced postprandial glycerol reduction, but otherwise none of the fibre preparations affected the postprandial lipemia. Extruded bread, based on wholegrain wheat flour, with high availability of in vitro starch, elicited a greater glucose response than wholegrain wheat bread, associated with a modest increase of GIP and insulin and with a stimulated early glucagon secretion. Flaked rye seemed to contain both faster and slower carbohydrates than the corresponding rye bread of similar fibre content. Analyses of the glucose curves suggested that the effect of fibre might be mediated by an effect on glucose absorption and parallel experiments in rat indicated that a delayed rate of gastric emptying might contribute. Further, the liver glycogen content was higher in rats given a slowly absorbed gastric load. A realistic increase in fibre content, given in long-term treatment, improved the metabolic control in NIDD patients, by decreasing the fasting blood glucose and LDL-cholesterol levels, as well as the LDL/HDL ratio. Hypothetically, slower absorption achieved with dietary fibre increases the proportion of glycogen in the liver. This postprandial improvement may cause the long-term trend to normalization of the fasting blood glucose level. PMID- 2889324 TI - [Rupture of the tibiofibular syndesmosis without osseous fibular injury]. AB - Within 3 years 12 injuries of the anterior fibulo-tibial ligament without fracture of the fibula were recorded prospectively. In relation to the total number of the ankle joint fractures during the same period the incidence is 3.3%. The rupture of the ligament arose in all cases from a forced eversion combined with supination or pronation of the foot. Clinical characteristics are the circumscribed painful palpation of the area of the ligament together with eversion pain of the foot. Arthrography is the most sensitive diagnostic procedure, which, however, may be avoided if the clinical situation is absolutely clear. Differential diagnosis consists mainly in the rupture of the fibulo-talar ligament including a tear of the anterior capsule of the ankle joint. Treatment should always be surgical - suture of the ligament, reinforcement of the syndesmosis by means of a positioning screw. Aftercare is functional without external fixation. PMID- 2889325 TI - [Surgical management of fresh injuries of the outer ligament of the upper ankle joint in local anesthesia]. AB - Fresh, isolated external ligament ruptures in adults have been surgically treated almost without exception under local anaesthesia for more than a year now at the Department of Surgery of the Rhenish-Westphalian Technical University (RWTH) at Aachen. No complications due to anaesthesia developed in these 119 patients; all of them expressed great satisfaction at this mode of surgical approach. What is more: this method is less costly and requires less personnel than surgery under peridural anaesthesia or intratracheal (intubation) anaesthesia. Hence, in the authors' opinion, isolated fresh ruptures of the outer ligaments of the ankle joint should be operated on more often under local anaesthesia than is actually being done at present. PMID- 2889327 TI - [Implant changes in sliding endoprostheses]. AB - Analysis of 6 failures of resurfacing gliding prostheses of the knee with necessary exchange operations. By this procedure of exchange of the loosened parts of the alloplasty, a good functional result could be achieved with the exception of one case. Importance of careful preoperative indication of gliding prostheses of the knee, where axis deviations of the leg as well as instability of the collateral ligaments should be particularly observed. PMID- 2889326 TI - [Dislocation of the patella--causality in legal accident insurance]. AB - Fifty-two expertises on connections between cause and effect of patellar dislocations were examined with a view to improving the standards of medical expertizing. On principle, the mechanism of injury is the decisive criterion in determining whether the injury can be considered capable of causing the dislocation. It was found that in about one-half of the cases the dislocation was wrongly attributed to the event and that a reasonable connection existed in only one-quarter of the cases. The typical causes of error in reasoning - first dislocation, impressive pattern of injury, no degenerative changes - are listed and discussed. The importance of the pattern of damage for the first occurrence of a dislocation is demonstrated. The suitability of different courses of events for contributing essentially to the dislocation is discussed. PMID- 2889328 TI - [Cement-free implanted total hip endoprosthesis of the Mittelmeier model. Clinical experiences and results following 6 years of use mainly in accident induced hip changes]. AB - We give a review of the results of 165 implantations in 143 patients. Uncemented endoprostheses (type Mittelmeier) for replacement of hip joints were implanted from September 1979 to December 1985 at the Berufsgenossenschaftliche Unfallklinik Frankfurt/Main. When we started to implant uncemented prostheses the complication rate was higher than in conventional implantations. Most of the complications could be gradually avoided. The current complication rate is equal in both procedures. Long-term results will be known in a few years' time. We will they also know whether the method is advantageous for younger patients. PMID- 2889329 TI - [Surgical treatment of tumor-induced destruction of the spine]. AB - Surgery for treatment of destructions of the spine varies depending on localization and tumour status. If the body of the vertebra is affected, the ventral approach allows radical tumour resection as far as possible. The following stabilization is effected by filling the defect and carrying out osteosynthetical fusion. Of 38 patients, three had benign tumours, whereas ten patients had primary malignant and 25 had metastatic tumours. The results show that surgical treatment is justified also in palliative indications; although survival time is not prolonged, the quality of life can be improved. PMID- 2889330 TI - [Rupture of the distal tibiofibular syndesmosis without ankle fracture]. AB - Rupture of the distal tibiofibular syndesmosis without fracture of the fibula may be a rare event, but in the presence of certain clinical signs, it should be investigated (pain and haematoma above the syndesmosis, pain at eversion and dorsal flexion, history of dislocation of the joint). The diagnostic procedure of choice is the arthrography of the ankle-joint. A so-called isolated posterior tibial fragment may lead to the diagnosis of a complex ligamentous injury. PMID- 2889331 TI - Antiallergic action of TMK-777, a leukotriene biosynthesis inhibitor. PMID- 2889332 TI - Effect of somatostatin on prostaglandin E2 gastric intraluminal release in humans. PMID- 2889333 TI - Leukotrienes in Crohn's disease: effect of sulfasalazine and 5-aminosalicylic acid. PMID- 2889334 TI - Cholinergic influence on prostaglandin E2 stimulated duodenal bicarbonate in the conscious rat. PMID- 2889335 TI - Activity changes of vasoactive autacoids during passage through the human fetoplacental vasculature. PMID- 2889336 TI - In vitro effect of octadecatrienoic acid on human platelet function. PMID- 2889337 TI - Plasticity of prostaglandin E2 receptor in human macrophages and the ternary complex of adenylate cyclase. PMID- 2889338 TI - New evidence with selective agonists and antagonists for the subclassification of PGE2-sensitive (EP) receptors. PMID- 2889339 TI - Solubilization, separation, and reconstitution of brain prostaglandin E2 receptor and GTP-regulatory component. PMID- 2889340 TI - [Neurotransmitters and the lower urinary tract]. PMID- 2889341 TI - Esmolol: a titratable short-acting intravenous beta blocker for acute critical care settings. AB - Esmolol (Brevibloc) is an intravenous, short-acting, titratable, cardioselective beta blocker with a very rapid onset and offset of action (t1/2 = 9.2 minutes). Esmolol-induced beta blockade can be maintained as long as infusion is continued. It exhibits neither intrinsic sympathomimetic activity nor significant membrane stabilizing activity. It is rapidly metabolized by an esterase in the erythrocyte cytosol to an inactive acid metabolite. Its hemodynamic and electrophysiologic effects are similar to those of other beta blockers. Unlike the effects of other beta blockers, however, the effects of esmolol dissipate rapidly to baseline within 30 minutes after its discontinuation. Evidence obtained from clinical studies indicates that esmolol is effective and safe in reducing the ventricular rate in patients with supraventricular tachyarrhythmias, and in reducing the heart rate in patients with acute myocardial infarction and/or unstable angina. Esmolol has also been shown to be effective and safe in attenuating the tachycardia and hypertension seen during the intraoperative period. Data from postoperative patients indicate that esmolol is ideal as sole-agent therapy for the treatment of moderate postoperative hypertension associated with a hyperdynamic state. The short duration of action and titratability of esmolol make it an ideal drug for use in patients in whom the clinical need for beta blockade is limited in duration, and it offers additional safety in patients in whom beta blockade is beneficial; however, it might be precluded because of coexisting contraindications. To date, experience with esmolol in over 1200 patients has been gathered, and the adverse effect profile is basically similar to that reported here. PMID- 2889342 TI - Choice of antihypertensive drug therapy. PMID- 2889343 TI - Arrhythmias as predictors of sudden death. AB - Two methods are available for exploring arrhythmias in cardiac patients who are at risk of sudden death: Holter monitoring and invasive electrophysiology. Despite numerous studies, the predictive value of these techniques, in terms of prognosis, remains poor for many reasons. Neither technique considered individually can give reliable prognostic indications simply because each technique addresses different issues which are only partially involved in the mechanism of sudden death. Invasive electrophysiology, by artificially provoking an arrhythmia, detects the potential substrate which may ultimately lead to lethal arrhythmias. Although this is an important technique it is insufficient because merely identifying the substrate for an arrhythmia does not necessarily mean that arrhythmia will occur. On the other hand, ambulatory ECG allows monitoring of spontaneous arrhythmias which may be considered as potential initiating factors in arrhythmias. However, even if initiating factors and potential substrates are present, they are not sufficient conditions to cause lethal arrhythmias to occur. When there is an opportunity to scrutinize the mechanism of arrhythmias which are indeed lethal, as in sudden death, it appears that the lethal event results from the intervention of a new factor which was either absent or not considered during preceding investigations. In coronary patients, curiously, ischemia more often provokes cardiac arrest or an electromechanical dissociation rather than a ventricular tachycardia or fibrillation. Sudden death is not infrequently of iatrogenic origin, because of the arrhythmogenic effect of powerful antiarrhythmic drugs. More important, ventricular fibrillation often occurs in the setting of a progressively increased sympathetic tone, which explains either the particular seriousness of a previously known arrhythmia or the occurrence of an arrhythmia which was never before observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889344 TI - The role of drugs in countering adverse pathophysiological profiles: influence on hemodynamics. PMID- 2889345 TI - Beta blockers and left ventricular hypertrophy in hypertension. AB - It is now generally accepted that hypertension-induced left ventricular hypertrophy (LVH) represents a phenomenon of multifactorial origin. Antihypertensive therapy with beta-blocking drugs influences most of the factors involved in the control of left ventricular mass. Therefore, although initial animal experiments yielded conflicting results, it is not surprising that a great deal of evidence has been accumulated in clinical studies showing that successful long-term antihypertensive treatment with beta blockers induces regression of LVH in hypertensive subjects. Differences in molecular structure among various beta blocking agents do not seem to influence this property. On the contrary, the question of whether reversal of LVH represents a beneficial or harmful byproduct of antihypertensive treatment with beta blockers is still unanswered. Animal and clinical studies suggest that left ventricular systolic function is unchanged or even improved after regression of LVH, whereas the ability of the heart to withstand recurrence of hypertension is slightly reduced. Furthermore, development of LVH in hypertensive subjects is associated with abnormalities in diastolic function which are not reduced by reversal of LVH induced by antihypertensive treatment with beta blockers. PMID- 2889346 TI - The influence of non-beta-blocking drugs on the lipid profile: are diuretics outclassed as initial therapy for hypertension? AB - Diuretic drugs, when used in the treatment of hypertension, raise the blood concentrations of total cholesterol and low-density or very low-density lipoprotein cholesterol. Triglycerides often increase as well. Thiazide, phthalimidine, loop, potassium-sparing, and methylindoline drugs produce a similar effect. Only indapamide, a methylindoline agent with vasodilator activity, has been free of adverse lipid effects. It remains unclear whether it is the low dose of indapamide or some other quality that frees it of this effect. In long-term diuretic therapy, total cholesterol returns to, or below, baseline values, suggesting that the lipid elevations are transitory. However, in studies with adequate control groups, total cholesterol declines below baseline valves in control subjects such that an adverse differential in lipid values persists in long-term treatment. Selective alpha-1-adrenoceptor-blocking drugs cause no change or favorable alterations in lipid concentrations in short-term and long term (1 year) treatment. Among all antihypertensive drugs, this class of agents, and especially prazosin, has produced the most consistently salutary lipid and metabolic effects. Although less well examined, guanabenz, clonidine, guanfacine, and diltiazem have been associated with favorable lipid changes. Captopril and nifedipine have caused no change in lipid-lipoprotein values in limited investigations. These agents are preferable to diuretics and certain beta blockers with respect to short-term effects on lipids and lipoproteins. Their ultimate superiority as monotherapy depends on whether they lower blood pressure equally well. Lowering of the probability of coronary heart disease in hypertensive patients depends as much on blood pressure control as on lipid effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889347 TI - Coronary arteriography performed by a physician assistant. AB - Funding constraints and an oversupply of cardiologists mitigate against continued training of increasing numbers of cardiology fellows. In some institutions, the workload of the catheterization laboratory is an overriding factor. The ability of a physician assistant to perform some of this work was tested to determine if the number of fellows and the content of the fellowship training program could be uncoupled from the catheterization laboratory workload. Among the first 150 patients in whom coronary arteriography was performed by a physician assistant, no patient died or had a myocardial infarction or stroke. Two patients (1.3%) had minor complications: a retinal embolus and an infected puncture site. The complication rate in 150 consecutive cases performed by fellows was also 1.3%, a small myocardial infarction and a transient ischemic attack. Procedure times for the physician assistant and for the fellows were 41 +/- 13 and 44 +/- 18 minutes for preoperative patients and 62 +/- 24 and 70 +/- 20 minutes for postoperative patients. Corresponding fluoroscopy times were 11 +/- 5 and 12 +/- 7 minutes for the preoperative and 22 +/- 12 and 20 +/- 6 for postoperative patients. Only preoperative fluoroscopy times were statistically different (p = 0.02). Thus, substituting a physician assistant for a fellow to perform coronary arteriography is an option in institutions at which the number of studies exceeds the training needs of fellows. PMID- 2889348 TI - The specialized physician assistant: an alternative to the clinical cardiology trainee. PMID- 2889349 TI - Pharmacokinetic and pharmacodynamic properties of beta-blocking drugs influencing choice in treatment of systemic hypertension. AB - Diuretics and beta blockers are the mainstay in treating mild and moderate systemic hypertension, but there is controversy as to which should be used first. Recent evidence of an increase in sudden death and a greater number of intolerable side effects in the diuretic-treated groups in the Multiple Risk Factor Intervention Trial in the U.S. and the Medical Research Council Trial in Great Britain has prompted some to suggest beta blockers as first-line therapy. However, beta blockers also have side effects, such as decreased ventricular function in patients with mild heart failure, increased airways resistance in those with chronic obstructive lung disease, increased plasma lipids, in particular low density lipoprotein cholesterol, and increased problems in patients with peripheral vascular disease and those with diabetes requiring insulin treatment. Many new beta-blocking drugs with different pharmacokinetic and pharmacodynamic properties allow the physician to choose the best one for each patient. beta-blocking drugs with long durations of action, high levels of bioavailability, beta 1 selectivity and intrinsic sympathomimetic activity appear most suitable for therapy. Cardioselectivity is suggested for patients with obstructive lung disease and peripheral vascular disease, and diabetic patients who take insulin. Long durations of action permit infrequent administration and recently agents with intrinsic sympathomimetic activity have been shown to have less effects on plasma lipid levels. Acebutolol also reduces ventricular arrhythmias, and may therefore be used to reduce sudden death in patients with coronary artery disease. The pharmacokinetic and pharmacodynamic properties of beta-blocking drugs can indicate the most appropriate choice for hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889350 TI - Effects of adrenoceptor-blocking drugs on plasma lipoprotein concentrations. AB - Evidence from numerous clinical trials has indicated that beta-adrenoceptor blocking agents without intrinsic sympathomimetic activity increase plasma triglycerides and decrease high density lipoprotein cholesterol in patients with hypertension or coronary artery disease. There appears to be little or no difference between the nonselective and cardioselective drugs in this regard. In contrast, beta blockers with intrinsic sympathomimetic activity and alpha 1 blockers appear not to have these effects. The changes induced by adrenoceptor blocking agents in lipid and lipoprotein metabolism and their possible significance in relation to the pathogenesis of coronary artery disease are discussed. PMID- 2889351 TI - Antihypertensive therapy and the concept of total cardiovascular protection. AB - Drug-induced reduction of elevated blood pressure decreases cardiovascular mortality and morbidity in patients with moderate and severe hypertension. Furthermore, antihypertensive drug studies in mild hypertensive subjects (diastolic blood pressure 90 to 104 mm Hg) have shown protection against stroke, left ventricular hypertrophy, congestive heart failure and progression of renal damage, as well as improved patient longevity. The Hypertension Detection and Follow-up Program trial, recently carried out in the U.S., documented reduced coronary artery disease events (fatal and nonfatal) in special drug-treated patients with mild hypertension. From the standpoint of practical management and considering the ubiquity of essential hypertension, a modified stepped-care regimen advocating initial drug therapy with a beta blocker and addition of low dose thiazide diuretic when necessary constitutes a judicious approach for widespread application. Although there are 8 orally active beta blockers currently approved in the U.S. for clinical use in systemic hypertension, only acebutolol possesses all of the salutary pharmacologic properties of cardioselectivity, intrinsic sympathomimetic activity and hydrophilicity, thereby making this compound an effective and safe beta-blocking agent for first-order management of a broad segment of the hypertensive population. PMID- 2889352 TI - Treatment of systemic hypertension. AB - Most patients with high blood pressure (BP) can be managed by using one of 4 classes of compounds: a diuretic, beta blocker, converting enzyme inhibitor or calcium antagonist. It is becoming clear, however, that different patients respond to different drugs and that side effects also vary from 1 patient to another. In many patients in whom 1 drug is not sufficient to lower BP, the combination of a low dose of 2 drugs, particularly a diuretic combined with a beta blocker or a converting enzyme inhibitor, is an effective way of decreasing BP further. An understanding of the mechanisms whereby drugs lower BP and why they are additive with some drugs and not with others is clearly important in the more rational use of drugs. The finding that much lower doses of drugs can be used is also important; the combination of a low dose of 2 drugs may not only be more effective in lowering BP but also have less side effects than a higher dose of a single drug. In patients with more resistant hypertension that is not controlled by 1 or 2 drugs combined, the next logical step is to add a third drug. Before doing this, however, it is important to check that the patient is complying with treatment and to consider secondary causes. Ideally, such patients should be referred to someone with a special interest in high BP as they are more likely to have an underlying cause for their hypertension. PMID- 2889353 TI - Short-term preoperative radiotherapy for adenocarcinoma of the rectum. An interim analysis of a randomized multicenter trial. Stockholm Rectal Cancer Study Group. AB - Between 1980 and 1985, 694 patients with clinically resectable rectal adenocarcinoma entered a controlled clinical trial of radiotherapy (25 Gy over 5 7 days) prior to surgery, as compared with surgery alone. At a median follow-up time of 34 months, the incidence of pelvic recurrence among 545 patients operated on "for cure" was significantly reduced in the radiotherapy group (p less than 0.01). The relative reduction rate was similar among patients with Dukes' A, B, and C tumors. No significant differences between the treatment groups were observed with regard to frequency of distant metastasis or survival. The postoperative mortality--defined as death within 30 days of surgery--was 7% in the radiotherapy group as compared to 2% in the group randomized to surgery only (p less than 0.01). This mortality mainly occurred among patients aged above 75 years, and the difference between the groups may have been due to the fact that the irradiated volume was fairly large. In younger patients, there was no significantly increased mortality with radiotherapy. PMID- 2889354 TI - Hepatic effects of drugs used in the treatment of peptic ulcer disease. AB - Although one member of the H2 blocker family (oxmetidine) proved to be intrinsically hepatotoxic, overt hepatic injury attributable to cimetidine and ranitidine is decidedly rare, given the tens of millions of patients who have received these medications. Even considering the fact that serious adverse reactions may be underreported by as much as a factor of 100, the number of reports submitted to the FDA-DDE of possible hepatic toxicity associated with these agents supports this low incidence. Whether or not a similarly low incidence will be seen with famotidine and the newer H2 receptor antagonists still under investigation must await additional clinical experience. The major effect of cimetidine on the liver is inhibition of the mixed function oxidase system responsible for the metabolism of many drugs and other compounds. Ranitidine and famotidine at usual doses do not appear to share the same drug interaction potential. Although cimetidine may potentiate the action of several medications with a narrow therapeutic range, possibly leading to clinical toxicity, its inhibitory effect on oxidative metabolism also appears to be the basis for its unique, potentially hepatoprotective role against injury due to acetaminophen and certain other hepatotoxins. Whether or not cimetidine will become clinically useful in the setting of acute acetaminophen overdose remains speculative at this time. The investigational drug, omeprazole, a substituted benzimidazole, is also capable of inhibiting the cytochrome P-450 system. Antacids, sucralfate, and other coating agents are devoid of any hepatotoxic potential, as they are essentially nonsystemic compounds. E-type prostaglandins currently under investigation for treatment of peptic ulcer disease do not appear to be intrinsically hepatotoxic, and, in fact, may have important hepatoregulatory and hepatoprotective properties. PMID- 2889355 TI - Cats--source of protection or infection? A case-control study of hemorrhagic fever with renal syndrome. AB - In the first case-control study analyzing risk factors in sporadic hemorrhagic fever with renal syndrome, 111 cases occurring in Shanghai in 1983 and 1984 and 136 matched controls were studied. Three factors were associated with risk of disease: travel in the month before onset of illness, intense exposure to rodents in the home, and cat ownership. Risk associated with cat ownership was not confounded by exposure to rodents in the home. Neither cat ownership nor risk associated with rodent exposure was confounded by history of travel. The role of cats as reservoir hosts of Hantaan virus is undefined, but this epidemiologic study indicates that infected cats may pose an important risk in the spread of this virus to humans. A survey of peridomestic animals in suburban Shanghai disclosed Hantaan virus infections in two rodent species and in an insectivore, Suncus murinus. PMID- 2889356 TI - An XXX male resulting from paternal X-Y interchange and maternal X-X nondisjunction. AB - A 2-year-old boy was found to have a 47,XXX karyotype. Restriction-fragment length-polymorphism analysis showed that, of his three X chromosomes, one is of paternal and two are of maternal origin. The results of Y-DNA hybridization were reminiscent of those in XX males in two respects. First, hybridization to Southern transfers revealed the presence in this XXX male of sequences derived from the Y-chromosomal short arm. Second, in situ hybridization showed that this Y DNA was located on the tip of the X-chromosomal short arm. We conclude that this XXX male resulted from the coincidence of X-X nondisjunction during maternal meiosis and aberrant X-Y interchange either during or prior to paternal meiosis. PMID- 2889358 TI - Treatment of diabetic diarrhea and orthostatic hypotension with somatostatin analogue SMS 201-995. AB - A diabetic patient was treated with a somatostatin analogue, SMS 201-995, to control chronic diarrhea and orthostatic hypotension. The patient was injected with 50 micrograms, 100 micrograms, and 150 micrograms of SMS 201-995 subcutaneously twice daily for three days at each dose. Stool weight decreased from a basal mean value of 906 g per 24 hours to 628 g, 445 g, and 408 g per 24 hours, respectively. Diarrhea remained suppressed for 18 months when the patient was last seen. When SMS 201-995 was then given at 5 micrograms to 10 micrograms per hour by continuous subcutaneous infusion, stool weight decreased to a mean of 321 g per 24 hours. Basal blood pressure, which averaged 99/71 mm Hg, rose to 133/91 mm Hg five minutes after 75 micrograms of SMS 201-995 was injected subcutaneously; it remained elevated for six hours after injection. Serum motilin levels decreased significantly from 126 pg/ml before injection of SMS 201-995 to 52 pg/ml after injection. Serum norepinephrine levels rose from 50 pg/ml supine (normal range, 150 to 550 pg/ml) and 52 pg/ml erect before injection of SMS 201 995 to 72 pg/ml supine and 110 pg/ml erect after injection. SMS 201-995 may raise blood pressure, in part by increasing the release of circulating norepinephrine. PMID- 2889357 TI - Distribution of beta-thalassemia mutations in south China and their association with haplotypes. AB - DNA from 93 Chinese beta-thalassemia chromosomes were hybridized to eight different mutant oligomers to determine their specific mutation. Four mutations accounted for 87% of the chromosomes; in descending frequencies, these mutations were codon 41/42, IVS-2 nt654, codon 17, and -28. Since codon 41/42 mutation can be associated with multiple beta-thalassemia haplotypes, codon 41/42 is probably a hot spot for the 4-bp deletion. The distributions of these mutations were mapped to various regions in south China. These data are useful for the planning of prenatal diagnosis programs in other Chinese communities worldwide. PMID- 2889359 TI - Regulation of guanylate cyclase by atrial natriuretic factor and the role of cyclic GMP in vasodilation. PMID- 2889360 TI - Renal hemodynamics and natriuresis induced by the dopamine-1 agonist, SKF 82526. AB - The intrarenal infusion of dopamine (DA) during alpha- and beta-adrenergic blockade has been reported to increase renal blood flow (RBF) and sodium excretion by occupation of DA-1 receptors. In addition, DA may potentially influence renal function by occupation of DA-2 receptor subtypes. This study was designed to examine the hemodynamic and/or tubular mechanisms of the natriuretic effect of DA-1 in dogs anesthetized with pentobarbital. The intrarenal infusion of the DA-1 agonist, SKF 82526 (10(-9), 10(-8), 10(-7) M), resulted in dose related increases in RBF and absolute and fractional sodium excretion. These changes were not associated with alterations in urinary prostaglandin E2, F2 alpha, or kallikrein excretion. To determine the role of RBF in the natriuresis due to SKF 82526 infusion (10(-7) M), the renal artery was constricted to return RBF to control levels during continued SKF 82526 infusion. Although absolute and fractional sodium excretion decreased during this maneuver, they remained higher than control. These studies support both a hemodynamic and a tubular mechanism for the natriuretic effect of the DA-1 agonist, SKF 82526. These effects do not appear to be mediated by the renal prostaglandin or kallikrein systems. PMID- 2889361 TI - Neuroanatomic localization of the inhibitory effect of TRH on growth hormone secretion. AB - The inhibitory effect of centrally administered thyrotropin-releasing hormone (TRH) on the plasma growth hormone (GH) response to GH-releasing hormone (GHRH) in the rat was studied in relation to the anatomic loci involved. Experiments were performed in animals with bilateral electrolytic lesions in the medial preoptic (MPO) area or with anterolateral hypothalamic deafferentation and in sham-operated controls. Blood samples were obtained every 10 to 20 min from and drugs were injected into freely moving animals with indwelling cannulas in the right atrium and lateral cerebral ventricle. In control animals, the plasma GH response to GHRH, 1 microgram iv, was almost completely inhibited by TRH, 1 microgram icv, injected 5 min previously. In animals with either MPO lesions or anterolateral hypothalamic deafferentation in which median eminence somatostatin immunochemical staining was almost completely eliminated, the GH response to GHRH was enhanced and TRH did not exhibit any inhibitory effect. These results, together with the previous observation that the inhibitory effect of TRH is blocked by prior treatment with anti-somatostatin serum, suggest that the effect of TRH is mediated by stimulation of somatostatin-containing neurons in the periventricular nucleus of the MPO area. PMID- 2889362 TI - Myometrial desensitization after ritodrine infusion. AB - We have developed a model in pregnant sheep to investigate pharmacological agents used for suppression of preterm labor. This model allows repetitive determinations of uterine contractility and simultaneous measurements of myometrial receptor and postreceptor events. We used the model to study the beta adrenergic agent ritodrine. We infused 11 pregnant sheep with ritodrine and 3 with physiological saline for 24 h. Oxytocin boluses were given before and at 5 and 22 h after onset of the infusion. Myometrial biopsies were obtained before and immediately after the infusion. After 22 h of ritodrine infusion, uterine contractility in response to the same oxytocin bolus was 50% greater than at 5 h (P less than 0.02). Myometrial membrane beta-adrenergic receptor density decreased 49% (P less than 0.005), and catecholamine-stimulated adenylate cyclase activity was reduced 70% (P less than 0.005). The model thus demonstrates that use of the beta-adrenergic agonist ritodrine in a clinically relevant manner results in tachyphylaxis of its effects on both physiological parameters and the receptor cascade system. PMID- 2889363 TI - Effect of somatostatin on glucose homeostasis in conscious long-fasted dogs. AB - The effects of somatostatin plus intraportal insulin and glucagon replacement (pancreatic clamp) on carbohydrate metabolism were studied in conscious dogs fasted for 7 days so that gluconeogenesis was a major contributor to total glucose production. By use of [3-3H]glucose, glucose production (Ra) and utilization (Rd) and glucose clearance were assessed before and after implementation of the pancreatic clamp. After an initial control period, somatostatin (0.8 microgram . kg-1 . min-1) was infused with intraportal replacement amounts of glucagon (0.42 ng . kg-1 . min-1) and insulin. The insulin infusion rate was varied to maintain euglycemia and then kept constant (68 +/- 16 microU . kg-1 . min-1) for 250 min. Plasma glucagon was similar (84 +/- 14 and 89 +/- 19 pg/ml) before and during somatostatin infusion, while plasma insulin was lower (9.3 +/- 0.9 and 6.6 +/- 0.5 microU/ml, P less than 0.05). Plasma glucose levels remained similar (89 +/- 2 and 96 +/- 9 mg/dl), while Ra and Rd and the ratio of glucose clearance to plasma insulin were significantly (P less than 0.05) increased (from 2.18 +/- 0.12 to 3.21 +/- 0.35 and 2.30 +/- 0.09 to 3.26 +/ 0.38 mg . kg-1 . min-1, and 0.30 +/- 0.03 to 0.59 +/- 0.11, respectively). Net hepatic lactate uptake and [14C]alanine plus [14C]lactate conversion to [14C]glucose increased (P greater than 0.05) (from 9.32 +/- 0.47 to 16.54 +/- 2.97 mumol . kg-1 . min-1 and 100 to 263 +/- 37%, respectively). In conclusion, somatostatin alters glucose clearance in 7-day fasted dogs, resulting in changes in several indices of carbohydrate metabolism. PMID- 2889364 TI - Effect of somatostatin on nonesterified fatty acid levels modifies glucose homeostasis during fasting. AB - In the 7-day fasted conscious dog, unlike the postabsorptive conscious dog, somatostatin infusion results in decreased levels of nonesterified fatty acids (NEFA) and increased glucose utilization (Rd) even when insulin and glucagon levels are held constant. The aim of this study was to determine whether NEFA replacement in such animals would prevent the increase in Rd. In each of three protocols there was an 80-min tracer equilibration period, a 40-min basal period, and a 3-h test period. During the test period in the first protocol saline was infused, in the second protocol somatostatin was infused along with intraportal replacement amounts of insulin and glucagon ("hormone replacement"), while in the third protocol somatostatin plus the pancreatic hormones were infused with concurrent heparin plus Intralipid infusion ("hormone replacement + NEFA"). Glucose turnover was assessed using [3-3H]glucose. The peripheral levels of insulin, glucagon, and glucose were similar and constant in all three protocols; however, during somatostatin infusion, exogenous glucose infusion was necessary to maintain euglycemia. The NEFA level was constant during saline infusion and decreased in the hormone replacement protocol. In the hormone replacement plus NEFA protocol, the NEFA level did not change during the first 90-min period and then increased during the second 90-min period. Rd was constant during saline infusion, increased in the hormone replacement protocol, but was constant in the hormone replacement plus NEFA protocol. After a prolonged fast in the dog, 1) somatostatin directly or indirectly inhibits adipose tissue NEFA release and causes a decrease in the plasma NEFA level, and 2) this decrease in the NEFA level causes an increase in Rd. PMID- 2889365 TI - Role of somatostatin neurons in intestinal peristalsis: facilitatory interneurons in descending pathways. AB - The role of somatostatin neurons in the regulation of peristalsis was examined in segments of rat colon that permit separate characterization of the ascending contraction and descending relaxation components of the peristaltic reflex. Release of somatostatin and vasoactive intestinal peptide (VIP) increased significantly only during descending relaxation. Preincubation of the segment with somatostatin antiserum (final concentration 1:40) decreased VIP release and descending relaxation. Addition of somatostatin (1 nM to 1 microM) augmented VIP release and descending relaxation in a concentration-dependent manner. Together the results implied that the increase in somatostatin release was coupled to, and responsible for, the increase in VIP release, which in turn was responsible for descending relaxation. The results are consistent with the topography of myenteric VIP neurons (which project into circular muscle) and somatostatin neurons (which project caudad within the plexus) and the pharmacological properties of the two peptides. Somatostatin antiserum had no effect on basal VIP release or ascending contraction, indicating that somatostatin neurons were not involved in the regulation of ascending contraction. The study suggests that somatostatin neurons of the myenteric plexus act as facilitatory interneurons in descending pathways. PMID- 2889366 TI - Glycine-extended progastrin processing intermediates: accumulation and cosecretion with gastrin. AB - Glycine-extended intermediates of peptide processing serve as substrates for carboxyl-terminal amidation, hence activation, of many brain-gut peptides. To explore the dynamics of accumulation and secretion of these important intermediates we utilized primary cultures of canine antral mucosal G-cells as a model system. Glycine-extended progastrin processing intermediates (G-Gly) accumulated rapidly in G-cells cultured in ascorbate-deficient media, exhibiting a fourfold increase over a 51-h culture period, while gastrin content fell to less than half of the initial level. In contrast, G-cells cultured in ascorbate supplemented media accumulated G-Gly at a relatively low rate, while gastrin was preserved at a higher level. Under either condition, G-Gly and gastrin were progressively released into the culture media. The release of both immunoreactivities could be stimulated by bombesin and inhibited by somatostatin in similar fashion. By electron microscopy, the cultured G-cells exhibited no ultrastructural alterations. These data suggest that 1) the cellular homeostasis of G-Gly is regulated by the activity of an ascorbate-dependent amidation enzyme similar to one previously described in pituitary tissues, 2) carboxyl-terminal amidation is not an obligatory step for secretion of gastrin, and 3) the proportions of gastrin and G-Gly cosecreted from G-cells reflect their proportional accumulation within G-cell secretory granules. The physiological relevance of the released G-Gly has yet to be determined. PMID- 2889367 TI - Inhibitory control of proximal colonic motility by the sympathetic nervous system. AB - The purpose of this study is to determine whether or not the sympathetic nervous system provides a tonic inhibitory input to the colon in chloralose-anesthetized cats. Proximal and midcolonic motility were monitored using extraluminal force transducers. An intravenous bolus injection of 5 mg of phentolamine in 14 animals elicited a pronounced increase in proximal colon contractility. The minute motility index changed from 0 +/- 0 to 26 +/- 4 after phentolamine administration. Midcolonic motility also increased in response to phentolamine. Specific blockade of alpha 2-receptors, but not alpha 1-receptors, caused the same response seen with phentolamine. alpha-Adrenergic blockade increased colon contractility after spinal cord transection but not after ganglionic blockade. Blockade of alpha-adrenergic receptors was also performed before vagal and pelvic nerve stimulation and in both cases increased colonic motility. Vagal stimulation alone had no effect on colonic contractility, while pelvic nerve stimulation increased motility at the midcolon. alpha-Receptor blockade did not alter the ineffectiveness of vagal stimulation but did unmask excitatory effects of pelvic nerve stimulation on the proximal colon. All excitatory colonic responses were prevented by blocking muscarinic cholinergic receptors. These data indicate that tonic sympathetic nervous system activity exerts an inhibitory effect on colonic motility. The inhibitory effect is mediated through alpha 2-adrenergic receptors. Based on these findings, we suggest that alterations in sympathetic nervous system activity may be extremely important for the regulation of circular muscle contractions in the colon. PMID- 2889368 TI - Facilitatory role of efferent renal nerve activity on renal sensory receptors. AB - The effects of decreasing and increasing efferent renal nerve activity (ERNA) on the renorenal reflex responses to stimulation of renal mechanoreceptors (MR) (increased ureteral pressure) or renal chemoreceptors (CR) (retrograde ureteropelvic perfusion with 0.9 M NaCl) were examined in anesthetized rats. During prevailing ERNA, renal MR stimulation increased ipsilateral afferent renal nerve activity (ARNA) from 6 to 41 counts/s (spike counter) (n = 37) and from 2 to 6 resets/min, (voltage integrator) (n = 23), contralateral urine flow rate from 5.3 to 7.4 microliters . min-1 . g-1 (n = 38) and urinary sodium excretion from 0.7 to 1.1 mumol . min-1 . g-1 (n = 38) (all P less than 0.01), without affecting mean arterial pressure or contralateral glomerular filtration rate. Similar results were obtained with renal CR stimulation. Decreasing ERNA 74 +/- 4% by hexamethonium, 10% body weight isotonic saline volume expansion, or inflation of a balloon at the junction of right atria and superior vena cava abolished the increase in ipsilateral ARNA and the contralateral diuresis and natriuresis produced by stimulation of renal MR or CR. Increasing ERNA 254 +/- 120% (peak response, n = 15, P less than 0.01) by placing the rat's tail in 53 degrees C water increased basal ARNA 249 +/- 80% (n = 6, P less than 0.05) and enhanced the ipsilateral ARNA response 202 +/- 78% (n = 9, P less than 0.01) to renal MR stimulation. These results indicate that ERNA exerts a facilitatory effect on renal MR and CR and their afferent renal nerve fibers in the renorenal reflexes. PMID- 2889369 TI - Baroreflex mechanisms buffering alpha-adrenergic agonists in conscious dogs. AB - To determine the relative importance of the mechanisms utilized by the arterial baroreflex in buffering the pressor and vasoconstrictor responses to alpha adrenergic receptor agonists, we studied responses to norepinephrine and phenylephrine in conscious dogs. The dogs were studied 2-8 wk after instrumentation with aortic catheters and aortic electromagnetic flow probes to measure arterial pressure and cardiac output. Total peripheral resistance was calculated on-line by a digital computer. The dogs were studied after beta adrenergic receptor blockade (propranolol 1.0 mg/kg) to eliminate the complicating inotropic effects of the agonists studied. Norepinephrine (0.2 microgram/kg bolus) increased mean arterial pressure by 30 +/- 3 mmHg, total peripheral resistance by 51 +/- 4 mmHg . l-1 . min-1, and decreased heart rate by 26 +/- 3 beats/min. After arterial baroreceptor denervation, norepinephrine increased mean arterial pressure by 69 +/- 8 mmHg, total peripheral resistance by 48 +/- 6 mmHg . l-1 . min-1, and heart rate did not change. After ganglionic blockade (hexamethonium 40 mg/kg), norepinephrine increased mean arterial pressure by 76 +/- 3 mmHg, total peripheral resistance by 47 +/- 4 mmHg X l-1 X min-1, and heart rate did not change. Only after elimination of the buffering by heart rate by use of cholinergic receptor blockade (atropine 0.1 mg/kg) or ventricular pacing could buffering of the vasoconstrictor responses to alpha adrenergic receptor agonists be demonstrated. Thus in conscious dogs the primary mechanism for buffering increases in arterial pressure induced by alpha adrenergic receptor agonists is compensatory changes in heart rate and cardiac output with little buffering of total peripheral resistance. PMID- 2889370 TI - Vasoconstrictor role for vasopressin in conscious, sodium-depleted rats. AB - To define the role of vasopressin as a vasoconstrictor hormone in sodium depletion, systemic hemodynamics and regional blood flow distribution were examined in conscious Sprague-Dawley rats after 6 days of a low-sodium diet. Studies were performed after selective or combined blockade with the vasopressin antagonist [d(CH2)5Tyr(Me)]AVP (AVPA), enalaprilat (CEI), and phentolamine (PHENTOL). Plasma levels of vasopressin were increased significantly after CEI and increased further after PHENTOL and CEI plus PHENTOL. AVPA had no effect on blood pressure, whether given alone or in the presence of PHENTOL, CEI, or CEI plus PHENTOL. Significant falls in peripheral vascular resistance associated with reflex increases in cardiac output were observed when AVPA was given to animals pretreated with either CEI or PHENTOL but not both. AVPA alone produced no significant changes in regional blood flow distribution, but a vasoconstrictor action of vasopressin in the renal vascular bed was revealed after prior treatment with CEI or PHENTOL. Muscle blood flow was also increased in the PHENTOL plus AVPA group compared with the PHENTOL group. No significant additional effects of AVPA were revealed by pretreatment with CEI, PHENTOL, or CEI plus PHENTOL for mesenteric, hepatic, splenic, or cerebral vascular beds. It is suggested that vasopressin acts as a vasoconstrictor hormone in conscious sodium-depleted rats when either the renin-angiotensin system or alpha-adrenergic system is inhibited but not when both systems are blocked. The renal vascular bed is an important site for vasopressin-induced vasoconstriction under these circumstances. PMID- 2889371 TI - Attenuation of baroreceptive mechanisms by cardiovascular sympathetic afferent fibers. AB - By sectioning spinal dorsal roots from C8 to T6, we analyzed the contribution of sympathetic cardiovascular afferent fibers to the reflex bradycardia induced by arterial pressure rises in 24 anesthetized and in 21 decerebrate cats. In anesthetized cats, the reflex bradycardia was obtained in 16 animals with occlusions of the thoracic aorta and in 8 animals with phenylephrine injections (25-75 micrograms/kg). In both experimental conditions, the dorsal root section enhanced the bradycardia response, which thus increased from 15 +/- 3 to 20 +/- 3% during aortic constrictions and from 11 +/- 3 to 19 +/- 6% during phenylephrine injections (P less than 0.05). The enhancement, after rhizotomy of the reflex bradycardia during aortic occlusion, was more pronounced in eleven decerebrate cats as it increased from 21 +/- 4 to 34 +/- 4%, P less than 0.05. In five vagotomized and decerebrate cats, the reflex bradycardia was also increased after rhizotomy despite the overall reduction of the reflex response. In five decerebrate cats with beta-adrenergic receptor blockade (propranolol 0.2-0.4 mg/kg iv), aortic occlusion resulted in a small reduction in heart rate which was not significantly affected by dorsal root section. Our data indicate that excitatory reflexes mediated by dorsal roots are likely to modulate the inhibitory supraspinal reflexes that determine the heart rate reduction during acute rises in arterial blood pressure. PMID- 2889372 TI - Myocardial potassium uptake during alpha- and beta-adrenoceptor stimulation. AB - The changes in myocardial K+ balance during alpha- and beta-adrenoceptor stimulation were compared in 10 anesthetized open-chest pigs by intracoronary isoproterenol and phenylephrine infusions. K+ concentration was continuously recorded by polyvinyl chloride catheter-valinomycin minielectrodes in arterial and coronary sinus blood. The arterial-coronary sinus difference and accumulated myocardial K+ uptake were calculated after computerized data sampling. Isoproterenol (2.5 nmol/min ic) reduced coronary sinus K+ transiently to a nadir of 0.37 (0.23-0.53) mM (median and 95% confidence interval) below control. The accumulated K+ uptake amounted to 139 (63-215) mumol/100 g. After beta-blockade by propranolol, phenylephrine (100 nmol/min ic) induced a transient coronary sinus K+ lowering of 0.16 (0.13-0.21) mM and an accumulated K+ uptake of 30 (20 41) mumol/100 g, both values less than those of isoproterenol (P less than 0.001). Myocardial contractility increased only during isoproterenol infusion, arterial blood pressure rose slightly by phenylephrine, but changes in myocardial O2 extraction and lactate uptake did not indicate cardiac ischemia. We conclude that both alpha- and beta-adrenoceptor stimulation induce a myocardial K+ uptake presumably due to increased Na-K pump activity, the latter more efficiently. PMID- 2889373 TI - Altered intracellular adrenoceptor distribution in myocardium of spontaneously hypertensive rats. AB - The number of membrane-bound beta-adrenoceptors is reduced in the myocardium of spontaneously hypertensive rats, and this decline may account for the decreased inotropic responsiveness to beta-agonists. It is not known, however, whether the total complement of cellular beta-receptors is lower in hypertensive animals. This issue was examined using two different approaches: acid elution of cell surface-bound beta-receptor ligands and comparison of the number of receptors in the plasma membrane and a postcytosolic vesicular fraction. Approximately 30% of the total beta-receptors were located intracellularly in Wistar-Kyoto rats compared with 42% for spontaneously hypertensive rats. Similarly, a decline in membrane-bound beta-receptors in hypertensive rats was balanced by a rise in receptors associated with the vesicular fraction. In contrast, alpha 1 adrenoceptors were higher in the membrane and lower in the vesicular fraction of hypertensive rats without a significant difference in total alpha-receptors compared with normotensive animals. Differences in adrenergic responsiveness in this, and perhaps other, models of cardiac hypertrophy reflect altered intracellular distribution of adrenoceptors, which may be under the control of the sympathetic nervous system. PMID- 2889374 TI - Persistent fetal pulmonary hypoperfusion after acute hypoxia. AB - To determine the effects of duration of hypoxia on fetal pulmonary blood flow and vasoreactivity, we studied the response of the fetal pulmonary vascular bed before, during, and after prolonged (2-h) and more brief (30-min) exposures to acute hypoxia in 19 chronically instrumented unanesthetized fetal lambs. Left pulmonary arterial blood flow was measured by an electromagnetic flow transducer. Fetal PO2 was lowered by delivering 10-12% O2 to the ewe. During 2-h periods of hypoxia left pulmonary arterial blood flow decreased, and main pulmonary arterial and pulmonary vascular resistance increased. The increase in pulmonary vascular resistance was sustained throughout the 2-h period of hypoxia. After the return of the ewe to room air breathing, pulmonary vascular resistance remained elevated for at least 1 h despite the rapid correction of hypoxemia and in the absence of acidemia. In contrast, after 30 min of hypoxia, left pulmonary arterial blood flow, pulmonary arterial pressure, and pulmonary vascular resistance returned to base-line values rapidly with the termination of hypoxia. The persistent pulmonary hypoperfusion after 2 h of hypoxia was attenuated by alpha-adrenergic blockade and was characterized by a blunted vasodilatory response to increases in fetal PO2. When fetal PO2 was elevated during the posthypoxia period in the presence of alpha-blockade, pulmonary blood flow still remained unresponsive to increases in fetal PO2. We conclude that 2-h periods of acute hypoxia can decrease fetal pulmonary vasoreactivity, and we speculate that related mechanisms may contribute to the failure of the normal adaptation of the pulmonary circulation at birth. PMID- 2889375 TI - Cortical control of thermogenesis induced by lateral hypothalamic lesion and overeating. AB - Increased O2 consumption was found in rats after bilateral lesions of the lateral hypothalamus (LH) or during voluntary overeating. This phenomenon appears to be mediated by the sympathetic nervous system (SNS) in both conditions, since it is blocked by the beta-blocker propranolol administration. In the first experiment we showed that the brain cortex is involved in the thermogenesis induced by LH lesion and this effect is mediated by SNS, since bilateral functional decortication induced by cortical-spreading depression (CSD) impaired the increase of O2 consumption to the same extent as administration of propranolol. In the second experiment the role played by the cerebral cortex on thermogenesis in rats during voluntary overeating of "cafeteria" diet and in control rats was investigated. Cafeteria rats showed a significantly higher colonic temperature, brown adipose tissue temperature (Tbat), and rate of O2 consumption than control animals. CSD led to a significant decrease of Tbat and O2 consumption in cafeteria rats but not in controls. On the basis of the results obtained in the two experiments, the possibility that the cerebral cortex could be involved in the metabolic responses for reduction of body weight to the "set-point" is hypothesized. PMID- 2889376 TI - Sustained remission in drug-free schizophrenic patients. AB - The inability to determine which schizophrenic patients do not require maintenance medication is a significant gap in current knowledge. This report describes 23 largely chronic DSM-III schizophrenic patients who, after a period of inpatient treatment, sustained good outcome without maintenance antipsychotic medication over an average of 15 years. Retrospective study of these patients revealed that their distinguishing characteristics at admission included better premorbid social and occupational adjustment, higher levels of accrued psychosocial competence and acquired skills, fewer hebephrenic traits, and the preservation of affect (depressed mood). Hence, even within a largely chronic patient sample, classic predictors of good outcome may also be useful in predicting sustained remission without medication. PMID- 2889377 TI - CSF somatostatin in patients with Alzheimer's disease, older depressed patients, and age-matched control subjects. AB - Somatostatin-like immunoreactivity was measured in the CSF of 12 patients with Alzheimer's disease, 15 age-matched control subjects, and 20 older depressed subjects. Patients with dementia or depression were found to have lower CSF somatostatin concentrations than control subjects despite markedly different clinical presentations. Severity of depression was clearly different in all three groups but showed no significant correlation with CSF concentration of somatostatin. There was a significant positive correlation between CSF somatostatin-like immunoreactivity and cognitive functioning in all 47 subjects, but this association was not statistically significant within individual diagnostic groups. These data raise interesting questions about possible biological links between Alzheimer's disease and depression in older patients. PMID- 2889378 TI - Frequency and presentation of neuroleptic malignant syndrome: a prospective study. AB - In an 18-month prospective assessment of 679 hospitalized, neuroleptic-treated patients, the authors, using previously defined operational criteria, diagnosed neuroleptic malignant syndrome in six cases (0.9%). This supports their earlier finding that the syndrome appeared in about 1% of neuroleptic-treated patients. PMID- 2889379 TI - Neuroleptic malignant syndrome and lethal catatonia. PMID- 2889380 TI - Diagnosing and defining neuroleptic malignant syndrome. PMID- 2889381 TI - Prevalence of neuroleptic malignant syndrome. PMID- 2889382 TI - Reducing antipsychotic drug prescribing for nursing home patients: a controlled trial of the effect of an educational visit. AB - We conducted a statewide, controlled trial of the efficacy of an educational visit in reducing antipsychotic drug prescribing for nursing home patients. Frequent antipsychotic drug prescribers were visited by a trained physician counselor who stressed known drug risks for elderly patients and suggested techniques for reducing antipsychotic drug use. Although well-received, the visit did not reduce antipsychotic drug prescribing. This negative finding suggests that future interventions address factors within the nursing home which encourage antipsychotic drug use. PMID- 2889383 TI - Growth hormone-releasing hormone (GHRH)-secreting pancreatic tumor in a patient with multiple endocrine neoplasia type I. AB - A growth hormone-releasing hormone (GHRH)-secreting pancreatic tumor in a 36-year old man, who had typical, familial, multiple endocrine neoplasia (MEN) type I with hyperparathyroidism and acromegaly, is described. The resected tumor, weighing 30 g, showed unusual histological features characterized by a meningioma like arrangement of crescent-shaped cells and contained many cells that reacted with C-terminal specific antibody to GHRH-44 and a few somatostatin immunoreactive (IR) and calcitonin-IR cells, but no GH-IR cells. A high concentration of IR-GHRH (9.8-13.2 micrograms/g wet weight tissue) with the full molecular size of GHRH-44 was detected in a tumor extract. Electron immunocytochemical study by the protein A-gold method revealed GHRH-IR granules with a mean diameter of 147 nm. After removal of the tumor, the plasma IR-GHRH level became normal (decreasing from 299 to 16.1 pg/ml) and the plasma IR-GH level also decreased, but still remained slightly high (decreasing from 42.4 to 9.6 ng/ml), suggesting the presence of an adenomatous lesion in the hypophysis. PMID- 2889384 TI - Immunological studies in amebiasis: isotypic characterization of specific antibodies by enzyme-linked immunofiltration assay. AB - Fifty sera from 17 cases of invasive amebiasis (15 hepatic localizations, 1 ameboma, 1 diffused colic localization) were studied by enzyme-linked immunofiltration assay (ELIFA). IgM and IgE anti-Entamoeba histolytica were detected in 10 and 15, respectively, of the 17 patients studied. IgM and IgE antibodies were found simultaneously in 10 cases; these 2 isotypes were only recognized twice in the same serum by the same antigenic components. During post therapy monitoring, in less than 90 days IgE or IgM-Ab regressed completely in half the cases. If they appeared or reappeared after the third month, prognosis was bad. In addition to its value for diagnosis and prognosis, the ELIFA allowed us to detect the functional antigenic components revealed more particularly by some IgG, IgM, IgE, or IgA antibodies. PMID- 2889385 TI - The electrophoretic isoenzyme patterns of strains of Entamoeba histolytica isolated in two major cities in Canada. AB - The isoenzyme patterns of 92 isolates of Entamoeba histolytica from British Columbia and 28 from Ontario were determined. Seropositivity for E. histolytica was assessed by indirect hemagglutination and enzyme-linked immunosorbent assay in the one center and by ELISA and amebic gel diffusion in the other. In both British Columbia and Ontario nonpathogenic zymodemes I and III were most common. A newly described isoenzyme pattern was identified in Ontario. Only 9 of 120 zymodeme patterns identified were found to be pathogenic strains of E. histolytica. Pathogenic isolates were strongly correlated with clinical symptoms and seropositivity. PMID- 2889386 TI - Further biochemical characterization of chronic Trypanosoma brucei gambiense Microtus montanus infection. AB - Tyrosine aminotransferase (TAT), glutamic-pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and alkaline phosphatase (ALP) were measured in the serum and livers of Microtus montanus infected with Trypanosoma brucei gambiense. Only liver TAT and serum ALP showed significant changes. In addition, blood glucose, pyruvate and lactate, and liver glycogen levels were assayed. All four compounds showed significant changes, strongly suggesting increased glycogen mobilization and increased catabolic activity. Interestingly, the serum ketone levels were very low and no significant changes were observed. These chronically infected animals had an organic aciduria in which pyruvate, lactate, beta hydroxybutyrate, alpha-ketoglutarate, phenylpyruvate, and p-hydroxyphenylpyruvate were significantly increased. The possible significance of these observations is discussed. PMID- 2889387 TI - Clorazepate therapy for intractable epilepsy. AB - Thirty-one epileptic patients with seizures refractory to conventional anticonvulsants were treated by adding clorazepate dipotassium to their regimen. Twelve cases showed improvement in seizure frequency, three of whom attained a seizure free state. Response to clorazepate was not related to the type of epilepsy, but patients with secondary generalized epilepsy tended to be less responsive than those with partial epilepsy. Among the various seizure types, generalized tonic-clonic seizures and simple partial seizures showed, although not significant, a tendency to be more responsive to clorazepate therapy than other seizure types, including complex partial seizures, atypical absence, atonic seizures, and tonic seizures. Drowsiness was the main adverse effect, of which 14 patients complained. Six patients were withdrawn from clorazepate because of drowsiness, but in the remaining 8 patients, this side effect disappeared within a week. The appearance of adverse effect was not related to the dose of clorazepate given. Clorazepate may be an effective secondary anticonvulsant in the treatment of intractable epilepsy. PMID- 2889388 TI - Effects of benzodiazepines on laryngeal reflexes. Comparison of lormetazepam and Diazemuls. AB - Of 20 volunteers, five were given intravenous Diazemuls 15 mg over 15 seconds, and three groups of five were given lormetazepam 2 mg intravenously over 10, 20 and 60 seconds, respectively. Laryngeal reactivity and psychomotor function were tested at intervals from prior to injection until 4 hours after injection. For equivalent degrees of depression of psychomotor function, lormetazepam depressed the laryngeal reflex less than Diazemuls (p = 0.004). Lormetazepam give over 60 seconds depressed the laryngeal reflex more than when given over 10 seconds (p = 0.008) or over 20 seconds (p = 0.048), although a significant difference was not demonstrated between the 10-second and 20-second groups. These results concur with experimental evidence that benzodiazepine receptor multiplicity exists, which allows various members of the benzodiazepine group of drugs to exhibit differing therapeutic ratios for their various effects. PMID- 2889389 TI - Comparison of two regional techniques for postoperative analgesia in children following herniotomy and orchidopexy. AB - This study compares the quality and duration of analgesia in two groups of patients aged between 1 and 13 years who received either caudal anaesthesia with plain bupivacaine 0.25% or an iliohypogastric and inguinal nerve block combined with skin infiltration using bupivacaine 0.25% with adrenaline 1:200,000. The results indicate no significant difference in the duration or quality of the analgesia provided by the two techniques. There was no difference in the incidence of vomiting or the time of first micturition between the two groups. PMID- 2889390 TI - Prolongation of neuromuscular blocking effect of vecuronium by antibiotics. AB - A case is described of prolonged neuromuscular block in a patient who was given the muscle relaxant vecuronium followed by bolus injections of the antibiotics gentamycin and clindamycin. PMID- 2889391 TI - Intranasal nitroglycerine attenuates pressor response to tracheal intubation in beta-blocker treated hypertensive patients. AB - The effect of intranasal nitroglycerine on the pressor response to laryngoscopy and tracheal intubation was studied in 40 adult hypertensive patients treated with beta-blocking drugs. Nitroglycerine 0.75 mg, administered intranasally 30 seconds before induction of anaesthesia, was compared with a placebo solution of saline. Haemodynamic variables were measured for 10 minutes after laryngoscopy and tracheal intubation. Heart rate did not change significantly in either group. Systolic as well as mean arterial blood pressure increased significantly for the first 5 minutes in the control group, whereas patients in the nitroglycerine group showed a decrease in systolic as well as in mean arterial pressure. No patient in the nitroglycerine group showed a decrease in systolic arterial pressure greater than 20 mmHg. In conclusion, intranasal nitroglycerine ameliorates the pressor response to laryngoscopy and tracheal intubation in beta blocked patients. PMID- 2889392 TI - [Antagonism of an intubation dose of vecuronium]. AB - To study the problem of rapid antagonization of an intubation dose of vecuronium (0.08 mg/kg), 36 surgical patients undergoing barbiturate/halothane anesthesia were given edrophonium 0.5, 0.75, and 1.0 mg/kg or neostigmine 0.04, 0.06, and 0.08 mg/kg precisely 5 min following injection of the muscle relaxant. T1 twitch (T1/Tc) and train-of-four (TOF) ratios (T4/T1) of the hypothenar muscle were monitored every 20 s with the aid of a commercially available EMG monitor (Datex Relaxograph). As documented by T1 and T4/T1 follow-up curves (Figs. 1 and 2) and derived parameters of relaxation as well (Dur25, Dur50, Dur75, recovery index, and reversal time; Table 4), both edrophonium and neostigmine resulted in a significantly shorter duration of vecuronium blockade (P less than 0.001). The mean time for recovery of TOF ratio to above 0.7 was between 10.8 +/- 6.0 (neostigmine 0.08 mg/kg) and 21.2 +/- 7.8 (neostigmine 0.06 mg/kg) min (mean +/- SD) following injection of the antagonist as compared to 58 +/- 18.4 min in the control group (P less than 0.001). Recurarization did not occur. Differences between drugs and dose-dependent effects were minimal; edrophonium did not prove superior to neostigmine with the exception of less pronounced muscarinic side effects, hence less bradycardia and a minimum heart rate of 57 +/- 8.2 bpm 20 min after the injection of neostigmine as opposed to 72 +/- 8.2 bpm following edrophonium (P less than 0.05; Fig. 4). As to the restitution of a ventilatory force sufficient to allow spontaneous breathing, no definite conclusions can be made.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889393 TI - [Intravenous anesthetics and human neutrophil granulocyte motility in vitro]. AB - Polymorphonuclear leukocytes (PMN) form a major part of the body's nonspecific first line of defense. An early event, prerequisite for the effective restriction of microbial invasions, is the chemotactic movement of activated neutrophils towards the invading organisms. To date, only limited and contradictory data exist regarding the effects of various intravenous anesthetic agents on neutrophil migration. In this study, the influence of ketamine, etomidate, midazolam, diazepam, and six commonly used i.v. barbiturates (hexo-, pheno-, pentobarbital, methohexital, thiopental, thiobutobarbital) on the in vitro motility of isolated human PMN was tested. Purified PMN (greater than 95%) were obtained from venous blood samples of healthy adults by dextran sedimentation, subsequent ammonium chloride treatment for red blood cell lysis, and Ficoll Hypaque gradient centrifugation. Random and chemotactic migration were assessed under 1% agarose in the presence of 10(-3)-10(-7) M logarithmic dilutions of the agents in antibiotic free migration medium (MEM). N-fMet-Leu-Phe (FMLP) served as the standardized chemical attractant (10(-7) M). PMN motility was unaffected by ketamine and etomidate, but a significant (P less than 0.001), dose - related depression could be observed with both benzodiazepines at concentrations exceeding 10(-5) M (Fig. 1). Except at 10(-3) M concentration, this migratory inhibition proved to be easily reversible (Fig. 3). At the highest concentration tested (10(-3) M), all the barbiturates caused a significant (P less than 0.001) but completely reversible depression of random as well as chemotactic PMN migration (Table 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889394 TI - [Status of postoperative pain therapy in West Germany. Results of a representative survey]. AB - To determine how pain is assessed and managed in the early postoperative period, what the prescribing habits and general opinions on postoperative pain are, and what suggestions for future improvement could be made, questionnaires were sent to 430 anesthesia departments in the FRG. Of these, 188 were returned (38% response). Systemic treatment (opiates, major and minor tranquilizers, peripherally acting analgesics and spasmolytics) was preferred in most cases, although regional anesthesia/analgesia seems to be rather popular. Data are given not only for analgesic techniques, but also for the most frequently used drugs. The study highlighted deficiencies in communication between the anesthetic staff and the patients that resulted in poor assessment of acute pain problems. The findings indicate a need to document pain and pain relief more often and more precisely in order to improve postoperative pain control. PMID- 2889395 TI - Tooth injury associated with anaesthesia. PMID- 2889396 TI - Dental damage during anaesthesia and surgery. AB - A review of the Accident Compensation Corporation (ACC) files on dental damage following anaesthesia or surgery was undertaken along with a survey of New Zealand anaesthetists asking about their practice with respect to protection of teeth during anaesthesia. These results confirm that damage is relatively common and that the majority of damaged teeth (62%) were known to have been previously restored, or weakened through periodontal disease prior to the damage occurring. The anaesthetists surveyed thought that dental damage was even more common than shown from the ACC records, and yet the vast majority of them did not routinely use specific protective guards and 45% of them did not ever use protective guards of any type. PMID- 2889398 TI - Glutamine and glutamate: automated quantification and isotopic enrichments by gas chromatography/mass spectrometry. AB - A method is described for simultaneous quantification of glutamine and glutamate plasma levels and isotopic enrichments in these compounds. Glutamine and glutamate are analyzed intact as their tertiary-butyldimethylsilyl derivatives. Deuterated glutamine and glutamate are used as internal standards for quantification by reverse isotope dilution. Preparation of plasma samples is accomplished by adding ammonium formate as an ion-pairing agent followed by extraction of the amino acids into 4.3:1 methanol:water. Negligible amounts of glutamine to glutamate conversion are observed during the sample preparation and GC/MS analysis. Since glutamine is analyzed intact, both single and double [15N]glutamine labels can be quantified. [15N]Glutamine at 0.2 to 11 mol% excess was measured in plasma with an average relative standard error of 3.8%, and [15N]glutamate over a range of 0.4 to 9 mol% excess was measured with a mean relative standard error of 12%. At glutamate levels above 1 mol% excess 15N, the mean relative standard error was 6%. Finally, automated sample injection into the GC/MS and automated data reduction are used for the analysis of samples by GC/MS. PMID- 2889397 TI - A clinical comparison of atracurium and vecuronium in women undergoing laparoscopy. AB - In a double-blind, prospective, randomised trial in 30 women undergoing laparoscopy, atracurium and vecuronium were compared in equipotent (2 X ED95) doses. In the atracurium group, first twitch depression was significantly greater at one minute, and degree of fade significantly greater at one and two minutes, but thereafter neuromuscular monitoring showed no significant difference between the groups. Clinically there was no significant difference between the drugs. Mild intraoperative hypotension was equally common in both groups as was sinus bradycardia. Reversal and recovery were comparable in the two groups. Neostigmine was required in all patients and in three (one atracurium, two vecuronium) a second dose was required in all patients and in three (one atracurium, two vecuronium) a second dose was administered on clinical grounds. Antagonism of the neuromuscular block is required with surgery of this duration despite the intermediate duration of action of the relaxant drugs. PMID- 2889399 TI - Determination of camazepam and bromazepam in human serum by adsorptive stripping voltammetry. PMID- 2889400 TI - Comparative development of gastrin and somatostatin cell populations in the pancreas, stomach, and duodenum of the rat during the perinatal period. AB - The comparative growth patterns of endocrine gastrin and somatostatin cell populations were examined in the rat, during the perinatal period, to investigate possible relationships between their development and that of gastric acid secretion, gastrin and somatostatin hormones being implicated in the regulation of acid secretion. Total cell populations were estimated daily in the pancreas, stomach, and duodenum, by using a quantitative morphological method, from 19 days postcoitum to 8 days postpartum. In the pancreas, both cell types were present at 19 days postcoitum. After increasing, gastrin cells abruptly dropped from 4 days postpartum, while somatostatin cells continued to increase. In the stomach, gastrin cells seemed to appear at 19 days postcoitum, increasing with age. Somatostatin cells appeared only after birth and could be precisely quantified from 4 days postpartum. In the duodenum, the two cell types were present in similar numbers at 19 days postcoitum and increased similarly with age. Comparison of gastrin and somatostatin cell developmental behavior with previous data on the ontogeny of acid secretion shows a parallelism between the appearance of basal H+ fluxes at 20-21 days postcoitum and the high daily multiplication of the gastrin cell number in the three organs. Additionally, the marked decrease of pancreatic gastrin cell population at 4 days postpartum and the simultaneous development of the gastric somatostatin cell population might explain, among other mechanisms, the diminution of gastric acid secretion noted after birth. PMID- 2889401 TI - Stimulatory effects of halothane and isoflurane on fluoride release and cytochrome P-450 loss caused by metabolism of 2-chloro-1,1-difluoroethene, a halothane metabolite. AB - The structural similarity of the halothane metabolite, 2-chloro-1,1 difluoroethene (CDE), to haloethenes that are metabolized by and inactivate cytochrome P-450, suggests that CDE may undergo secondary metabolism and degrade these isozymes. This possibility was examined in hepatic microsomes by determining fluoride release and cytochrome P-450 loss due to CDE metabolism in the presence of several anesthetics. CDE alone decreased cytochrome P-450 from phenobarbital-treated rats by as much as 37%, but the addition of isoflurane or halothane to incubations containing CDE increased the loss of cytochrome P-450 nearly twofold. Fluoride release was enhanced approximately 2.5 to 3 times by halothane or isoflurane; however, fluroxene inhibited fluoride release and did not enhance the loss of cytochrome P-450. Extrapolation of these results to the clinical situation suggests that the metabolism of CDE produced during halothane anesthesia and the accompanying cytochrome P-450 loss may contribute to the inhibition of drug metabolism produced by halothane. PMID- 2889402 TI - The effects of succinylcholine on mouth opening. AB - Mouth opening and the resistance to opening developed by the muscles of mastication were measured in 63 children anesthetized with halothane and relaxed with succinylcholine, pancuronium, or vecuronium. Measurement of mouth opening, induced by a constant test force, was made when each patient was deeply anesthetized, as judged by clinical parameters. Succinylcholine, vecuronium, or pancuronium was then administered. The mouth opening measurement was repeated immediately after the loss of limb muscle twitch response and 45 s following the loss of twitch response. For the 24 patients receiving succinylcholine, there was a significant reduction in mean mouth opening (P less than 0.0001) and a significant increase in jaw stiffness (P less than 0.0001) immediately after limb relaxation. Forty-five seconds after full limb relaxation was attained, the mean mouth opening was still reduced (P less than 0.0001) and the mean jaw stiffness was still increased (P less than 0.0003) in the succinylcholine group. Patients receiving either vecuronium or pancuronium did not show a significant change of mouth opening or jaw stiffness following limb relaxation. Three patients, who received succinylcholine, required several attempts at tracheal intubation due to increased resistance to mouth opening. Anesthesia and surgery proceeded in all patients. None of the patients developed malignant hyperthermia. In view of the fact that a reduction in mouth opening was a constant finding when succinylcholine was administered during halothane anesthesia, the assumption that isolated "masseter spasm" or jaw stiffness heralds malignant hyperthermia should be reconsidered. PMID- 2889403 TI - Continuous infusion of vecuronium: the effect of anesthetic agents. AB - The authors studied the effects of enflurane, isoflurane, and fentanyl, each in combination with 60% nitrous oxide, on the vecuronium infusion rate necessary to maintain constant 90% depression of control muscle twitch tension. Thirty healthy surgical patients were given an initial 0.1 mg/kg bolus of vecuronium, followed by an infusion of vecuronium at an initial rate of 1.0 microgram . kg-1 . min-1. After 1 h of steady-state 90% twitch depression, plasma vecuronium concentrations (Css90) were measured by capillary column gas chromatography. Total plasma clearance of vecuronium was estimated using Css90 values. Vecuronium infusion rates (mean +/- SD) were similar for patients given enflurane (0.28 +/- 0.13 microgram . kg-1 . min-1) and isoflurane (0.30 +/- 0.13 microgram . kg-1 . min 1), but significantly higher in patients given fentanyl (0.92 +/- 0.37 microgram . kg-1 . min-1). Values for Css90 in the patients receiving enflurane and isoflurane were similar (71 +/- 34 and 72 +/- 44 ng/ml, respectively), but significantly higher in those receiving fentanyl (165 +/- 48 ng/ml). Total plasma clearance was similar during enflurane, isoflurane, and fentanyl anesthesia (4.4 +/- 2.6, 4.6 +/- 1.2, and 5.6 +/- 1.9 ml X kg-1 min-1, respectively). The authors conclude that patients receiving isoflurane and enflurane require markedly lower vecuronium infusion rates to achieve 90% neuromuscular blockade than those receiving fentanyl. The enhancement of neuromuscular blockade by isoflurane and enflurane represents a change in the pharmacodynamics of vecuronium-induced neuromuscular blockade, rather than a change in pharmacokinetics. PMID- 2889404 TI - High-dose almitrine bismesylate inhibits hypoxic pulmonary vasoconstriction in closed-chest dogs. AB - The effect of almitrine bismesylate on the hypoxic pulmonary vasoconstrictor (HPV) response was studied in seven closed-chest dogs anesthetized with pentobarbital and paralyzed with pancuronium. The right lung was ventilated continuously with 100% O2, while the left lung was ventilated with either 100% O2 ("hyperoxia") or with an hypoxic gas mixture ("hypoxia": end-tidal PO2 = 50.1 +/- 0.1 mmHg). Cardiac output (CO) was altered from a "normal" value of 3.10 +/- 0.18 l . min-1 to a "high" value of 3.92 +/- 0.16 l . min-1 by opening arteriovenous fistulae which allowed measurements of two points along a pressure-flow line. These four phases of left lung hypoxia or hyperoxia with normal and high cardiac output were repeated in the presence and absence of almitrine. Almitrine bismesylate was administered as a constant infusion of 14.3 micrograms . kg-1 . min-1 for a mean plasma concentration of 219.5 +/- 26.4 ng . ml-1. Relative blood flow to each lung was measured with a differential CO2 excretion (VCO2) method corrected for the Haldane effect. With both lungs hyperoxic, the percent left lung blood flow (%QL-VCO2) was 44 +/- 1%. When the left lung was exposed to hypoxia, the %QL-VCO2 decreased significantly to 22 +/- 1%. However, with the administration of almitrine, the %QL-VCO2 during left lung hypoxia increased significantly to 36 +/- 2%. The arterial oxygen tension decreased significantly between hyperoxia (PaO2 = 633 +/- 6 mmHg) and hypoxia (271 +/- 31 mmHg). With the addition of almitrine, there was no change during hyperoxia; however, during hypoxia, the PaO2 decreased significantly to 124 +/- 15 mmHg. Cardiac output did not influence these findings. The pulmonary vascular conductance (G) is the slope of the pressure-flow line.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889405 TI - Heart rate and rhythm following an edrophonium/atropine mixture for antagonism of neuromuscular blockade during fentanyl/N2O/O2 or isoflurane/N2O/O2 anesthesia. PMID- 2889406 TI - Vecuronium: effect on intracranial pressure and hemodynamics in neurosurgical patients. PMID- 2889407 TI - The inhibition of stress-induced beta-endorphin secretion by histamine receptor antagonists. PMID- 2889408 TI - Evaluation of enzymes in serum and cerebrospinal fluid in cases of cerebrovascular accidents. AB - Gamma glutamyl transpeptidase (GGTP), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) were measured serially in the serum and cerebrospinal fluid (CSF) of 22 patients with fresh stroke and an equal number of age- and sex-matched healthy control subjects. It was observed that levels of these enzymes in the CSF of control subjects were very low but were significantly elevated (p less than 0.001) in both serum and CSF in patients with stroke. The elevation was greater in the CSF than in the serum and was maximum during the first four days of stroke. Thereafter, the enzymatic activity declined. Of all these enzymes, GGTP in CSF correlated best with the clinical picture. It was possible to differentiate between the ischemic and hemorrhagic type of stroke on the basis of CSF levels of GGTP (greater than 60.0 units in hemorrhagic stroke). There was no correlation between GGTP levels in CSF and serum or among GOT, GPT, and GGTP in CSF. It can be concluded, therefore, that estimation of GGTP in CSF is helpful not only in predicting the degree of cerebral damage and functional outcome of the patient following stroke but also in differentiating the type of stroke. PMID- 2889409 TI - Restriction fragment length polymorphisms in dairy and beef cattle at the growth hormone and prolactin loci. AB - Two bovine populations, a Holstein-Friesian dairy stock and a synthetic (Baladi X Hereford X Simmental X Charolais) beef stock, were screened for restriction fragment length polymorphisms (RFLPs) at the growth hormone and prolactin genes. Most RFLPs at the growth hormone gene are apparently the consequence of an insertion/deletion event which was localized to a region downstream of the structural gene. The restriction map for the genomic region including the growth hormone gene was extended. Two HindIII RFLPs at the growth hormone locus, as well as several RFLPs at the prolactin gene, seemed to be the consequence of a series of point mutations. The results are discussed in terms of the possibility that minor genomic variability underlies quantitative genetic variation. PMID- 2889410 TI - A partial cDNA clone for porcine glucosephosphate isomerase: isolation, characterization and use in detection of restriction fragment length polymorphisms. AB - A cDNA library for porcine skeletal muscle was established in the vector pBR322. The library was screened with an oligonucleotide probe coding for a hexapeptide from glucosephosphate isomerase (Gpi). A positive clone with an insert of about 450 bp and restriction sites for PstI, BamHI and PvuII was isolated. A 362-bp PstI fragment was sequenced and shown to contain the codons for the hexapeptide as well as the remaining 29 amino acids of this Gpi peptide. The PstI fragment was used to probe pig genomic DNA. The restriction enzymes PvuII and SacI detected a set of polymorphisms with five bands, behaving as a set of insertion/deletion polymorphisms. PMID- 2889412 TI - Alterations in selected serum biochemical constituents in equids after induced hepatic disease. AB - Effects of induced cholestasis and hepatocellular necrosis and of fasting on serum biochemical constituents including bile acids, IgA, bilirubin, alkaline phosphatase, gamma-glutamyltransferase (GGT), arginase, and the clearance of sodium sulfobromophthalein were studied in 4 groups of equids. The reference value for serum bile acids, as determined by an enzymatic colorimetric procedure for horses and ponies was 5.94 +/- 2.72 mumol/L, there being no statistical difference for horses and ponies. Sample collection at time of feeding had no effect on serum bile acid concentration. Seemingly, serum bile acids, arginase, and GGT were the most sensitive indicators of cholestasis and/or hepatocellular necrosis and would form an essential minimum effective battery of tests to diagnose and prognose hepatic disease in equids. These tests provided a measure of hepatobiliary transport function (bile acids), cell necrosis (arginase), and cholestasis (GGT and bile acids). PMID- 2889411 TI - [Macroenzymes in human plasma. 2. Macrogamma-glutamyltransferase, macroalanine aminopeptidase, macroalkaline phosphatase, macroaminotransferases and other macroenzymes]. AB - The authors propose here the second part of the review concerning the plasma macroenzymes. Informations are given about the high-molecular mass forms of gamma glutamyltransferase (GGT), alanine aminopeptidase (AAP), alkaline phosphatase (ALP), aminotransferase, acid phosphatase and glucose-6-phosphatase dehydrogenase. For almost all these enzymes, the presence of enzyme immunoglobulins complexes may be observed in some plasma, but a specific immune character of these complexes has not always been proved. The membrane origin of GGT, AAP and ALP is responsible for the existence of special circulating macroforms: enzyme-lipoproteins associations due to the amphiphilic nature of some forms of these enzymes, and complexes between enzymes and membrane components. Although the knowledge about the structure of all these macroenzymes is increasing, the clinical interest to consider their existence because of the diagnostic uncertainties they may induce. PMID- 2889414 TI - Effect of beta-agonists and anticholinergic drugs on bronchial reactivity. PMID- 2889413 TI - Changes in autacoid and neuropeptide contents of lung cells in asbestos-induced pulmonary fibrosis. AB - The purpose of this study was to determine if asbestos-induced pulmonary fibrosis in the rat can affect the levels of autacoids and peptides in freshly isolated lung cells. Lung fibrosis was experimentally induced in rats by a single intratracheal instillation of 5 mg UICC Canadian chrysotile B fibers. Isolated lung cells were prepared from normal and from asbestos-exposed rats. These cells were also fractionated on bovine serum albumin (BSA) gradients. The contents of serotonin (5-HT), histamine (HIST), vasoactive intestinal peptide (VIP), and bombesin (BN) were measured in isolated total cell preparations as well as in density-fractionated cell populations from normal and from asbestos-exposed rats. Analysis of total lung cell preparation showed the presence of heterogeneous populations in normal rat lung. After asbestos exposure, there were significant changes in these cell populations as evidenced by significant increases in lymphocyte and mast cell numbers. In addition, increased levels of 5-HT, HIST, and VIP were observed in isolated lung cells obtained from rats exposed to asbestos 1, 3, and 6 months after instillation. BN content was unchanged 3 months after treatment, but was significantly increased at the 6 month-interval, suggesting a different pattern of response for this neuropeptide. Density fractionation of various cell populations further showed selective changes in specific cell fractions of lung after asbestos exposure. At 6 months, increased levels of 5-HT, HIST, and VIP were associated with cell fraction 7, whereas changes in BN content were found in cell fractions 2 and 3. Similarly, there was a significant increase of mast cells in fraction 7 at the 6-month interval.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889415 TI - Airway responsiveness in infancy. PMID- 2889416 TI - Ibuprofen interferes with the efficacy of antihypertensive drugs. A randomized, double-blind, placebo-controlled trial of ibuprofen compared with acetaminophen. AB - STUDY OBJECTIVE: To assess the effects of ibuprofen on blood pressure control in patients being treated with antihypertensive drugs. DESIGN: Randomized, blinded, placebo-controlled, parallel trial of ibuprofen compared with acetaminophen and with placebo in 3-week treatment periods. SETTING: A general internal medicine clinic at a university hospital. PATIENTS: Forty-five patients with essential hypertension controlled by treatment with at least two antihypertensive drugs were enrolled. Of these, 41 completed the study; treatment was discontinued in 3 of the 15 patients in the ibuprofen group due to breakage of the drug capsules, and after randomization in 1 of the 14 patients in the placebo group due to unstable angina. All 15 patients in the acetaminophen group completed the study. INTERVENTIONS: All previous antihypertensive regimens were continued. During the 3-week treatment, ibuprofen, 400 mg, was administered orally every 8 hours; acetaminophen, 1 g, orally every 8 hours; or placebo, 2 capsules, orally every 8 hours. MEASUREMENTS AND MAIN RESULTS: In the ibuprofen group, the mean increase from baseline after 3 weeks of treatment was significant in the average supine diastolic blood pressure (6.4 mm Hg; 95% confidence interval [CI], 1.05 to 11.75; p = 0.0239); supine mean arterial pressure (6.6 mm Hg; 95% CI, 1.25 to 11.95; p = 0.0205); and sitting mean arterial pressure (5.8 mm Hg; 95% CI, 1.57 to 10.04; p = 0.0123). The mean increase in blood pressure variables in the ibuprofen group was significantly different compared with the mean increase in the variables in the placebo group after 3 weeks of treatment: supine systolic blood pressure (7.1 mm Hg compared with -4.5 mm Hg; 95% CI for the difference in means, 2.5 to 20.6; p = 0.0133); supine diastolic pressure (6.4 mm Hg compared with 0.0; 95% CI for difference in means, 0.87 to 12.4; p = 0.0250); supine mean arterial pressure (6.6 mm Hg compared with -1.5; 95% CI for difference in means, 2.0 to 14.2; p = 0.0110); sitting systolic pressure (6.8 mm Hg compared with -3.7; 95% CI for difference in means, 2.0 to 19.0; p = 0.0169); sitting diastolic pressure (5.3 mm Hg compared with -1.1; 95% CI for difference in means, 0.76 to 12.1; p = 0.0273); and sitting mean arterial pressure (5.8 mm Hg compared with -2.0; 95% CI for difference in means, 1.5 to 14.1; p = 0.0169).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2889417 TI - Factors that affect the induction of gamma glutamyltransferase in epileptic patients receiving anti-convulsant drugs. AB - Serum samples from 335 epileptic patients receiving one or more anticonvulsant drugs, phenobarbitone, primidone and phenytoin, have been analysed for biochemical liver profile (BLP) and serum drug concentration. The results show that the induction of serum gamma glutamyltransferase (GGT) is affected by the sex and age of the patient, type of anti-convulsant drug prescribed and duration of treatment. It is less affected by serum drug concentration. It is suggested that these factors must be considered when interpreting results involving serum GGT activity as the index of microsomal enzyme induction. PMID- 2889418 TI - Stress, coronary disease, and coronary death. AB - Evidence of a positive association between cardiovascular illness and psychological stress presented in the literature is generally not totally convincing, which in part is due to methodological problems in defining and measuring psychophysiological and psychosocial variables. However, both reports in the literature and the clinical experience of most physicians present numerous examples of sudden, unexpected cardiac death, in which the event in all probability has been either induced or hastened by stressful life experiences. This applies to fatal and non fatal cardiac attacks, since both are often preceded by emotional stress. There is pathoanatomical evidence of specific myocardial damage induced by catecholamine release during stressful emotions. Histochemical studies have revealed copious amounts of noradrenaline stored in myocardium especially in patients with ischaemic heart disease. Epidemiological surveys on the relationships between life-stress and coronary mortality and morbidity have demonstrated certain positive associations in many cross-sectional studies as well as in certain prospective studies. Most positive evidence has been accumulated from studies on the influence of loneliness on cardiovascular morbidity and mortality. Animal experiments have demonstrated repeatedly that psychological stress evoked by aversive sensoric stimuli or unsuccessful social striving induce cardiovascular pathology including myocardial damage, hypertension, vascular changes and increased risk of sudden cardiac death. PMID- 2889419 TI - DNA polymorphisms in human population studies: a review. AB - The use of restriction endonucleases and DNA probes to expand the range of informative polymorphisms should be of immense value in the study of human populations. To date, this approach has been only minimally used, but results are available for markers in the major histocompatibility complex and the globin gene clusters. In addition, isolated studies using other probes have been published. The ease of the techniques involved, the rate at which new DNA polymorphisms are being found and the range of information provided should ensure that use of this approach expands rapidly. PMID- 2889421 TI - Relationship of simian T-lymphotropic virus type III to human retroviruses in Africa. PMID- 2889420 TI - Expression of cyclin (PCNA) and the phosphoprotein dividin are late obligatory events in the mitogenic response. AB - Analysis of the overall patterns of gene expression at the polypeptide synthesis level has revealed two S-phase specific, proliferation sensitive nuclear proteins [cyclin (PCNA) and dividin (phosphoprotein)] whose rate of synthesis increases at the G1/S transition border of the cell cycle. All available evidence suggests that expression of these proteins are late obligatory events in the mitogenic response. PMID- 2889422 TI - Muscles and their neural control. AB - The session on 'The Muscles and Their Neural Control' comprised papers that covered an extremely broad field, ranging from single membrane channels to integration at the motor unit level. To start with the molecular mechanisms, slow noninactivating sodium channels were postulated to be the common denominator in a number of myopathies, their activation causing depolarization and thus muscle weakness. New ideas were presented regarding muscle insulin receptors as the main target for neurotrophic influences, as well as transmitter release at nonmammalian motor nerve terminals. Changes in muscle compliance seem to be involved in adaptation of spindle sensitivity and reflex activity. Also, data were presented in favor of a neurotoxic component in myotrophic lateral sclerosis. Analysis of stationary motor unit discharges can differentiate parkinsonian patients without tremor from normal controls. Long-term use dependent factors that change muscle properties have considerable effects on the way in which contractile force is graded. PMID- 2889423 TI - Motor functions of the basal ganglia. AB - This session dealt with the structure and function of the basal ganglia and their role in motor control. The key issues discussed in the first four presentations concerned the pathophysiology of movement performance in parkinsonian patients and in animal models of this disease. Three papers were presented on neurochemically specified subsystems of the basal ganglia. Therapeutic aspects (stereoencephalotomy and chronic electrical stimulation of neural tissue) were discussed in the last two papers. A brief account is given on the highlights of each of these reports. PMID- 2889424 TI - Activation of Mg-ATP hydrolysis in isolated Rhodospirillum rubrum H+-ATPase. AB - The effects of lauryl dimethylamine oxide on the Rhodospirillum rubrum H+-ATPase have been studied. This detergent activates Mg2+-dependent ATP hydrolysis in the isolated R. rubrum F0-F1 34-fold, whereas the Ca2+-ATPase activity is only slightly modified. ATPase activation by lauryl dimethylamine oxide enhances the effect on ATP hydrolysis exerted by free Mg2+ ions. Concentrations of free Mg2+ in the range of 0.025 mM favor activation while higher concentrations inhibit ATPase activity by approximately 70%. Steady-state kinetic analysis shows that lauryl dimethylamine oxide induces a complex kinetic behavior for Mg-ATP in the chromatophores, similar to the untreated F0-F1 complex. The initial rate value for Mg-ATP unisite catalysis was found to be 6.3 times higher (3.5 X 10(-3) mol Pi per mol R. rubrum F0-F1 per second) in the presence than in the absence of detergent, where the initial rate was 5.5 X 10(-4) mol Pi per mol R. rubrum F0-F1 per second. These experiments show that lauryl dimethylamine oxide shifts the cation requirement for ATP-hydrolysis of the isolated R. rubrum H+-ATPase from Ca2+ to Mg2+ and that it activates both multisite and unisite catalysis. Results are discussed in relation to the possibility of a regulatory role by Mg2+ ions on ATP hydrolysis expressed through subunit interactions. PMID- 2889425 TI - Purification and characterization of tyrosine aminotransferase activities from Anchusa officinalis cell cultures. AB - Three activities of tyrosine aminotransferase (TAT; EC 2.6.1.5), the enzyme which catalyzes the first step of the tyrosine pathway leading to the formation of rosmarinic acid (alpha-O-caffeoyl-3,4-dihydroxyphenyllactic acid), have been extensively purified from cell suspension cultures of Anchusa officinalis L. and subsequently characterized. TAT-1, TAT-2, and TAT-3 differ slightly in native molecular weights (180,000-220,000) and are composed of subunits (4 X 43,000 for TAT-1 and 4 X 56,000 for TAT-2). All three enzymes show a pronounced preference for L-tyrosine over other aromatic amino acids, but TAT-2 and TAT-3 can also effectively utilize L-aspartate or L-glutamate as a substrate. For amino acceptor cosubstrates, either oxaloacetate or alpha-ketoglutarate can be utilized equally well by TAT-1, while the former is the most effective alpha-keto acid for TAT-2 and the latter is the best for TAT-3. All the TAT activities display high pH optima (8.8-9.6), and are inhibited by the tyrosine metabolite 3,4 dihydroxyphenyllactate. TAT-2 and TAT-3 are also inhibited by rosmarinic acid. PMID- 2889426 TI - Sezary-like syndrome in a 10-year-old girl with serologic evidence of human T cell lymphotropic virus type I infection. AB - A 10-year-old girl with a Sezary-like syndrome is described. At age 6 months, her skin involvement began as psoriatic plaques. Generalized erythema, lymphadenopathy, and pruritus developed into erythroderma. Her general condition has been good in spite of severe pruritus and erythroderma. Atypical cells were found in the peripheral blood in numbers of 2500/mm3 and were present in the dermis of a skin biopsy specimen. When examined by electron microscopy, these cells showed lobulated or indented nuclei and were similar to Sezary cells. The patient showed a high titer (1:1280) of antihuman T-cell lymphotropic virus type I antibody. Her mother was also positive with a titer of 1:40 and seems to be a healthy carrier. PMID- 2889427 TI - Immunoglobulin lambda light chain genes in rheumatoid arthritis. AB - Restriction fragment length polymorphisms (RFLPs) obtained by hybridisation of an immunoglobulin lambda constant region probe to Eco RI digests of genomic deoxyribonucleic acid (DNA) obtained from rheumatoid arthritis (RA) and control subjects have been compared. Polymorphic bands of 8, 13, 18, and 23 kb (kilobases) were shown. The 8/8 genotype and 8 kb allele were increased and the 8/18 genotype and 18 kb allele decreased in the RA group. This effect was independent of HLA and Gm. These findings suggest that genes linked to the loci for the immunoglobulin lambda constant region may influence susceptibility to RA. PMID- 2889429 TI - Cholesterol induced changes in glucose-6-phosphate generating enzymes, concanavalin A agglutinability and haemolytic activity of axenic Entamoeba histolytica. AB - Repeated passage of the 200-NIH strain of Entamoeba histolytica through cholesterol-enriched axenic growth medium induced marked increases in cholesterol, phosphoglucomutase and hexokinase levels and a less prominent rise in the protein content of amoebic cells. There was also pronounced enhancement of haemolytic activity and Concanavalin A (Con A) agglutinability of the culture, but no significant change was observed in glucose phosphate isomerase. These cholesterol-induced effects persisted to a large extent when amoebae were subsequently repassaged through normal axenic medium lacking exogenous cholesterol, but changes in cellular cholesterol and protein levels did not persist. Qualitatively similar results were obtained whether the sterol was layered as a film on the glass walls of the culture tubes or supplied as sonicated micells, but the latter was in general more effective. PMID- 2889428 TI - Management of NSAID induced gastrointestinal disturbance. PMID- 2889430 TI - Use of the automated tail suspension test for the primary screening of psychotropic agents. AB - Mice, when suspended by the tail, will alternate between active attempts to escape and immobility. A specially developed computerized device (ITEMATIC-TST) automatically measures the duration of immobility of 6 mice at one time and at the same time provides a measure of the energy expended by each animal, the power of the movements. Use of these 2 parameters enables activity profiles to be generated which can distinguish different classes of psychotropic activity. Immobility is decreased by antidepressants and psychostimulants, but increased by neuroleptics and minor tranquillizers. Minor tranquillizers can be distinguished from neuroleptics in that they decrease the power of the movements, whereas neuroleptics are without effect on this parameter. The present experiments were undertaken to see whether the activity profiles generated in this procedure could indeed be useful for primary psychotropic screening. Eighteen compounds, including antidepressants, neuroleptics, minor tranquillizers, sedative/hypnotics, dopaminergic stimulants and 3 dummy compounds were first submitted to a shortened primary observation procedure for dose finding and were then investigated at 2 doses in the automated tail suspension test. All experiments were conducted blind. The results obtained largely confirm the activity profiles already reported in this test and show that the combined use of primary observation and the automated tail suspension test permit the unambiguous identification of the pharmacological activity of 15 of the compounds tested with tentative identification of the 3 remaining compounds. PMID- 2889431 TI - Secretomotor and mucolytic effects of mabuterol, a novel bronchodilator. AB - Action of mabuterol, a novel bronchodilator, on the respiratory secretion system was investigated, and the following effects were confirmed: 1) increase of output volume, amounts of protein and pulmonary surfactant in respiratory fluid; 2) decrease of sputum viscosity; 3) fragmentation of the sputum structure and 4) promotion of the mucociliary transport of particles. The results in the present study may, at least partly, substantiate clinical efficacy such as improvement of pulmonary function, favourable effects on expectoration and amelioration of symptoms observed in patients with chronic obstructive pulmonary disease. PMID- 2889432 TI - A simplified in vitro assay correlating amebicidal activity with chelation by 8 hydroxyquinoline and related compounds. PMID- 2889433 TI - Interaction of pathogenic and nonpathogenic Entamoeba histolytica with human complement. PMID- 2889434 TI - Isoenzyme patterns of strains of Entamoeba histolytica isolated in British Columbia. PMID- 2889435 TI - The reliability of Entamoeba histolytica zymodemes in clinical laboratory diagnosis. PMID- 2889436 TI - [Neurobiological approach to anxiety]. PMID- 2889437 TI - [Pharmacology of anxiolytic agents in the cardio-vascular domain]. PMID- 2889438 TI - Cognitive dysfunction, negative symptoms, and tardive dyskinesia in schizophrenia. Their association in relation to topography of involuntary movements and criterion of their abnormality. AB - Little is known of factors that, on an individual basis, confer vulnerability to the emergence of involuntary movements (tardive dyskinesia) during long-term neuroleptic treatment. In this study of 88 chronic schizophrenic inpatients, 22 variables (four demographic, 14 medication history, and four features of illness) were compared for any association(s) with the presence, by differing topographies and criteria of abnormality, and severity of involuntary movements. Irrespective of the criterion used, the presence of marked cognitive dysfunction-muteness bore a consistent and highly significant primary association with both the presence and the overall severity of orofacial dyskinesia; no such association was found in relation to the presence of limb-truncal dyskinesia. Flattening of affect was the only other variable consistently associated with the presence of orofacial movements. The reliability and prominence of the association between the presence of orofacial, but not of limb-truncal, movements and cognitive dysfunction negative symptoms suggest that these varying topographies may not constitute a unitary syndrome. This strong association, not with indexes of neuroleptic exposure but rather with features of the illness for which that treatment was prescribed, suggests some neurologic process, more subtle than may previously have been appreciated, as a vulnerability factor of some importance. In schizophrenia it appears to be intimately related to the disease process. PMID- 2889439 TI - Tardive dyskinesia and steady-state serum levels of thiothixene. AB - The purpose of this investigation was to determine the relationship between serum levels of the neuroleptic agent thiothixene and tardive dyskinesia in schizophrenics of a wide age range. Forty-one male schizophrenic subjects, 21 with tardive dyskinesia and 20 without, were given a fixed dosage of thiothixene hydrochloride (10 mg orally four times daily) after a drug-free period of one week. Higher steady-state serum levels of thiothixene (obtained after five days of a fixed-dosage schedule) were associated with greater degrees of tardive dyskinesia. This relationship was independent of the relationship between tardive dyskinesia and age. PMID- 2889440 TI - Response of the mouse epididymal duct to the disappearance and reappearance of spermatozoa induced by temporal cryptorchidism. AB - Cryptorchid surgery to move the testis and epididymis to the abdomen was performed in mice of 60 days of age; one week later the mice were subjected to further surgery to reposition the organs in the scrotum. The mice were sacrificed at 1 week intervals until 11 weeks after the initial operation. After the first operation, spermatozoa in the epididymal duct rapidly disappeared and were almost absent until the 4th week. Then spermatozoa appeared again, increased, and reached normal numbers by 10 weeks. With the disappearance of the spermatozoa, a PAS-positive material, which is believed to be secreted in the middle part of the head of the epididymal duct (ABE et al., 1982), was accumulated in the epididymal duct in the body and tail of the epididymis, and PAS-positive inclusions appeared in the principal cells of the duct in the body 2 weeks after the first operation. The inclusions developed in size and number during the aspermia period, then decreased in number with the reappearance of spermatozoa from the 5th week to ultimately disappear by 10 weeks after the first operation. We have previously demonstrated that such inclusions appear also after efferent duct ligation, which interrupts the flow of spermatozoa and testicular fluid into the epididymal duct (ABE et al., 1982). Both present and previous findings indicate that the appearance of PAS-positive inclusions depends on the absence of spermatozoa in the epididymal duct irrespective of the presence of the testicular fluid in the duct. It is suggested that the PAS-positive material is utilized by spermatozoa and, in the absence of spermatozoa, is accumulated in the lumen and ingested by the principal cells of the epididymal duct in the body of the epididymis. PMID- 2889441 TI - Human T-cell lymphotropic virus type I-associated adult T-cell leukemia/lymphoma in an atypical host. AB - Human T-cell lymphotropic virus type I (HTLV-I) is a unique retrovirus associated with specific malignancies of T cells in humans. The virus is endemic to Japan, the Caribbean, Africa, and the southeastern United States. We report here the first case of HTLV-I-associated lymphoma in an atypical host. The incidence of antibodies in this individual with a T-cell malignancy strongly suggests HTLV-I virus as the causative agent. Direct identification of viral DNA using an HTLV-I specific probe provides definitive evidence of infection. PMID- 2889442 TI - [H2-antihistaminics. 35. Synthesis and H2-antagonistic action of imidazolylmethylthioalkyl-substituted 1,2,4-triazoles]. PMID- 2889443 TI - Maturation process of Japanese encephalitis virus in cultured mosquito cells in vitro and mouse brain cells in vivo. AB - The maturation process of Japanese encephalitis (JE) virus in C6/36 cells in vitro and in mouse brain cells in vivo was studied by electron microscopy. In the C6/36 cell infection, 500 to 2250 virions per cell were released into the medium during the period of study; yet, no virus budding process was observed at the host cell membranes. JE virions at various maturation stages appeared within the cisternae of rough endoplasmic reticulum (RER) of infected cells at 24 hours p.i.; and, although C6/36 cells did not show a well-developed Golgi apparatus, the virions appeared to be carried to the cell surface within host-cell secretory vesicles for extracellular release as early as 24 hours p.i. The occurrence of a secretory-type intracellular transport of maturing JE virus particles was well recognizable in brain cells of infected mice, in which JE virus particles were found almost exclusively in the cisternae of RER, in the Golgi apparatus, and in various vesicles, including coated vesicles, in the vicinity of the Golgi apparatus. Our previous study of dengue-2 virus morphogenesis and our present study of JE virus morphogenesis differed substantially at various stages of maturation. Possible mechanisms which explain these differences were discussed. PMID- 2889445 TI - [Immunoregulation by suppressor T cells: discovery of a new immunoregulatory system through internal imaging]. PMID- 2889444 TI - Restriction enzyme maps of the macropodid herpesvirus 2 genome. AB - The DNA of macropodid herpesvirus 2 (dorcopsis wallaby herpesvirus) was analysed using restriction enzymes and molecular cloning techniques. Sets of EcoRI and SalI clones were prepared which represented approximately 85 per cent of the genome, and these clones were used to map the DNA by double-digestion and hybridization experiments. Data on uncloned regions were obtained by analysing fragments excised from agarose gels, and terminal fragments were identified by exonuclease III digestion. The genome was shown to be approximately 135 kilobases (kb) long. It has a long unique sequence (95 kb) bounded by repeat sequences (5.5 kb) and joined at one end to a short unique sequence (15 kb) also bounded by repeat sequences (7.0 kb) in a manner similar to that of herpes simplex viruses 1 and 2. PMID- 2889446 TI - [APUD and mast cells of the gastrointestinal system: immunohistochemical and ultrastructural identification]. AB - A rationale for sequential immunohistochemical studies of the endocrine function of APUD cells is described, as exemplified by a study of serotonin-containing cells in rat small intestine, involving preparation of paraffin and semithin sections of epoxide resin-embedded tissue, followed by electron-microscopic examination of cells detected by the immunoperoxidase technique. With the approach described, it has been shown that a positive immunohistochemical reaction to antiserotonin antiserum is given, along with EC cells, by those mast cells disposed in groups near the EC cells as well as among connective-tissue cells of villi under the basement membrane. It is suggested that by collecting and accumulating the serotonin synthesized by specialized EC cells, mast cells transport it to sites of utilization as required by the specific arrangement. PMID- 2889447 TI - [RFLP: initial experiences in forensic molecular genetics]. PMID- 2889448 TI - [Forensic application of DNA fingerprints]. PMID- 2889449 TI - Atrial natriuretic factor and sodium nitroprusside increase cyclic GMP in cultured rat lung fibroblasts by activating different forms of guanylate cyclase. AB - We used cultured rat lung fibroblasts to evaluate the role of particulate and soluble guanylate cyclase in the atrial natriuretic factor (ANF)-induced stimulation of cyclic GMP. ANF receptors were identified by binding of 125I-ANF to confluent cells at 37 degrees C. Specific ANF binding was rapid and saturable with increasing concentrations of ANF. The equilibrium dissociation constant (KD) was 0.66 +/- 0.077 nM and the Bmax. was 216 +/- 33 fmol bound/10(6) cells, which corresponds to 130,000 +/- 20,000 sites/cell. The molecular characteristics of ANF binding sites were examined by affinity cross-linking of 125I-ANF to intact cells with disuccinimidyl suberate. ANF specifically labelled two sites with molecular sizes of 66 and 130 kDa, which we have identified in other cultured cells. ANF and sodium nitroprusside produced a time- and concentration-dependent increase in intracellular cyclic GMP. An increase in cyclic GMP by ANF was detected at 1 nM, and at 100 nM an approx. 100-fold increase in cyclic GMP was observed. Nitroprusside stimulated cyclic GMP at 10 nM and at 1 mM a 500-600-fold increase in cyclic GMP occurred. The simultaneous addition of 100 nM-ANF and 10 microM-nitroprusside to cells resulted in cyclic GMP levels that were additive. ANF increased the activity of particulate guanylate cyclase by about 10-fold, but had no effect on soluble guanylate cyclase. In contrast, nitroprusside did not alter the activity of particulate guanylate cyclase, but increased the activity of soluble guanylate cyclase by 17-fold. These results demonstrate that rat lung fibroblasts contain ANF receptors and suggest that the ANF-induced stimulation of cyclic GMP is mediated entirely by particulate guanylate cyclase. PMID- 2889450 TI - Stimulation of lysyl oxidase (EC 1.4.3.13) activity by testosterone and characterization of androgen receptors in cultured calf aorta smooth-muscle cells. AB - Previous studies have indicated a greater incidence of atherosclerotic cardiovascular disease in men than in women of child-bearing age, suggesting that vascular interactions with sex steroids may effect pathogenesis in these cases. In the present study, it was found that the presence of 10-100 nM-testosterone in the growth medium of calf aortic smooth-muscle cells in culture stimulates lysyl oxidase activity approx. 2.5-fold in the medium and 5.5-fold in the fraction bound to the cell layer. Androgen receptors were identified in these cultured smooth-muscle cells, and their properties were very similar to those in the cytosolic fraction of whole bovine aortic tissue. These receptors appeared to be specific for androgen, of high affinity (Kd = 0.4 nM) and of low capacity (9000 sites/cell). The present results indicate that the aortic smooth-muscle cell is a cellular target for androgens, and thus raise the possibility that the development of fibrotic arterial lesions involving the deposition of excess collagen may in part be regulated by androgen-mediated stimulation of collagen cross-linkage formation as catalysed by lysyl oxidase. PMID- 2889451 TI - Proctolin degradation by membrane peptidases from nervous tissues of the desert locust (Schistocerca gregaria). AB - The hydrolysis of the insect neuropeptide proctolin (Arg-Tyr-Leu-Pro-Thr) by enzyme preparations from the nervous tissue of the desert locust (Schistocerca gregaria) was investigated. Neural homogenate degraded proctolin (100 microM) at neutral pH by cleavage of the Arg-Tyr and Tyr-Leu bonds to yield Tyr-Leu-Pro-Thr, Arg-Tyr and free tyrosine. Arg-Tyr was detected as a major metabolite when the aminopeptidase inhibitors amastatin and bestatin were present to prevent Arg-Tyr breakdown. Around 50% of the proctolin-degrading activity was isolated in a 30,000 g membrane fraction and was shown to be almost entirely due to aminopeptidase activity. The aminopeptidase had an apparent Km of 23 microM, a pH optimum of 7.0 and was inhibited by 1 mM-EDTA and amastatin [IC50 = 0.3 microM], but was relatively insensitive to bestatin, actinonin and puromycin. Phenylmethanesulphonyl fluoride (1 mM) and p-chloromercuriphenylsulphonic acid (1 mM) had no effect on this enzyme activity. Although the bulk of the Tyr-Leu hydrolytic activity was located in the 30,000 g supernatant, some weak activity was detected in a washed membrane preparation. This peptidase displayed a high affinity for proctolin (Km = 0.35 microM) and optimal activity at around pH 7.0. Synaptosome- and mitochondria-rich fractions were prepared from crude neural membranes. The aminopeptidase activity was concentrated in the synaptic-membrane preparation, whereas activity giving rise to Arg-Tyr was predominantly localized in the mitochondrial fraction. The subcellular localization of the membrane aminopeptidase is consistent with a possible physiological role for this enzyme in the inactivation of synaptically released proctolin. PMID- 2889453 TI - Regulation of nerve growth factor synthesis/secretion by catecholamine in cultured mouse astroglial cells. AB - The nerve growth factor (NGF) synthesis/secretion by cultured mouse astroglial cells was modulated by catecholamine. In quiescent cells, epinephrine (EN) and dopamine (DA) markedly increased the NGF content in the conditioned medium (CM). Conversely, EN, DA, and norepinephrine (NE) decreased the NGF content in growing cells. Cholinergic agonists, metacholine and carbamylcholine, slightly increased the NGF content in quiescent cells, but showed no effects on growing cells. Other neurotransmitters tested had no effects on either growing or quiescent cells. These results suggest that catecholamine is one of the molecules responsible for regulation of NGF synthesis/secretion in the mouse brain. PMID- 2889452 TI - Influence of beta adrenergic blockers and their combinations with anticholinergic drugs on epileptiform activity in rabbit hippocampus. AB - The influence of alpha- and beta-receptor antagonists combined with drugs which act as antagonists at muscarinic and nicotinic receptor sites on epileptic focus produced by topic penicillin application was investigated. The beta-receptor blocking agent caused a faster and more intense activity of epileptogenic focus in comparison with activity in control animals, but the number of seizures decreased relatively for 25%. N-receptor antagonists diminished the facilitating effect of the beta-receptor antagonist on focal activity. Combination of m- and beta-receptor antagonists did not influence the spike activity of the focus. Treatment with alpha-receptor antagonists enhanced spikes and number of seizures only insignificantly. The combination of alpha- and n-receptor blocking substances does not influence the development of the epileptic process. The alpha receptor antagonist together with the m-receptor blocking drug induces a facilitation of spike activity. PMID- 2889454 TI - Evidence for imidazoline binding sites in basolateral membranes from rabbit kidney. AB - [3H]-RX 781094 and [3H]-rauwolscine, two potent alpha 2-adrenergic antagonists, were used to characterize alpha 2 receptor in basolateral membranes from rabbit kidney. However, the following findings suggest that the imidazoline [3H]-RX 781094 binds to an heterogeneous population of binding sites: 1) dissociation plot was biphasic with a fast and slow component, 2) in saturation experiments, [3H]-RX 781094 labels 3.5 more binding sites than [3H]-rauwolscine (p less than 0.02), 3) competition studies showed that molecules with imidazoline structure completely inhibited the [3H] RX 781094 binding; in contrast, only 25% of binding was affected by non-imidazoline alpha 2 adrenergic compounds. These results suggest that in basolateral membranes from rabbit kidney, [3H] RX781094 labels alpha 2 adrenergic and non-adrenergic receptors which might be imidazoline preferring binding sites. PMID- 2889455 TI - Activation of the Ha-ras gene in C3H 10T1/2 cells transformed by exposure to N methyl-N'-nitro-N-nitrosoguanidine. AB - A transfectable, presumably mutationally activated, c-Ha-ras gene was identified in a clonal population of 10T1/2 cells established from a Type II focus induced by exposure of a parental, wild-type population to N-methyl-N'-nitro-N nitrosoguanidine (MNNG). PMID- 2889456 TI - Dexamethasone effects on somatostatin receptors in pancreatic acinar AR4-2J cells. AB - The effects of glucocorticoids on somatostatin binding and cAMP response in the rat pancreatic acinar carcinoma AR4-2J cell line were examined. Dexamethasone treatment reduced the number of somatostatin receptors 2.5 fold without any change in receptor affinity. In addition, dexamethasone increased the sensitivity of the cells to somatostatin-inhibited cAMP formation and restored the biphasic pattern of cAMP response to somatostatin previously observed in normal pancreatic acinar cells. Such effect may be associated with the glucocorticoid-promoted cellular pancreatic differentiation of AR4-2J cells. PMID- 2889458 TI - Analgesic and respiratory effects of extradural sufentanil in volunteers and the influence of adrenaline as an adjuvant. AB - The effects of extradural sufentanil 50 micrograms were investigated in 10 normal volunteers. Eight of these were studied at a second session when adrenaline 1:200,000 was added to the sufentanil. Well-defined segmental analgesia developed rapidly after plain sufentanil and lasted approximately 3 h. Respiration was depressed for about the same period and was greatest in the first 2 h, as shown by a 15% increase in PECO2, while the slope and VE50 of the carbon dioxide response curve were depressed by 45% and 55%, respectively. Moderate drowsiness occurred in most subjects, while other side effects of itching, nausea and urinary retention occurred less frequently and were not severe. Addition of adrenaline 1:200,000 intensified segmental analgesia and prolonged duration to 5 h, while side effects were lessened. It is concluded that extradural sufentanil shows considerable promise for clinical use, and that the risk: benefit ratio is improved by adding adrenaline 1:200,000. PMID- 2889457 TI - [The anxiolytic action of phenoxypropanolamine derivatives in comparison with propranolol, diazepam and placebo]. AB - The hypothesis that the phenoxypropanolamine derivative CGP 361 A possesses anxiolytic activity was examined in 80 female healthy volunteers. Each volunteer received the treatment under double-blind conditions as part of a 1-way analysis of variance design. The medication factor had 4 levels (CGP 361 A, propranolol, diazepam and placebo). Stress was induced by asking subjects to deliver a free speech in front of a video camera. The anxiety was measured using adjectives list, state-trait-anxiety inventory and visual analogue scales. The physiological equivalents observed were pulse rate and skin resistance. The results support the hypothesis that a single dose of 10 mg CGP 361 A has a higher anxiolytic effect than 10 mg propranolol, 5 mg diazepam and placebo, with the peripheral beta blocking effects (established by pulse rate) being no stronger than with propranolol. No subjective or objective sedation has been determined under the different drug conditions. PMID- 2889459 TI - Peripheral vascular effects of beta-adrenoceptor blockade: comparison of two agents. AB - 1. The effects of atenolol (100 mg), a beta 1-adrenoceptor blocker, and bevantolol (200 mg) were compared on heart rate, blood pressure, lung function and on the peripheral circulation in normal volunteers before and after isoprenaline infusion. Recordings were obtained 2 and 24 h following a single dose and 24 h after continuous dosage for 7 days. 2. The effect of atenolol on the blockade of beta-adrenergic stimuli, as measured by the ability to reduce isoprenaline-induced tachycardia, was greater than that of bevantolol. Though both drugs achieved a similar reduction in systolic pressure there was a significantly greater reduction in diastolic pressure with bevantolol. The lung function tests gave similar results to those with other beta-adrenoceptor blockers. 3. Atenolol produced a fall in peripheral blood flow consistent with unopposed peripheral alpha-adrenoceptor stimulation. The effect of bevantolol differs from that of atenolol, an initial fall in peripheral blood flow being followed by a rapid recovery to baseline or greater. This effect may be due to partial alpha-adrenoceptor agonist activity. PMID- 2889460 TI - The effects and dose-response relationship of xamoterol in patients with ischaemic heart disease. AB - 1. In a double-blind placebo controlled four-way crossover study the effects and dose response relationships of xamoterol were studied in nine patients with angina and dyspnoea secondary to chronic left ventricular dysfunction. The duration of exercise on a treadmill and heart rate were measured at the end of each phase of the study at 2 h and 24 h after dosing. 2. Xamoterol at 200 mg and 400 mg orally once daily had no effect on the mean resting heart rate but there was a small (5.7 beats min-1) but significant reduction in resting heart rate on 600 mg at 2-2.5 h after dosing. All three doses of xamoterol significantly reduced the maximum exercise heart rate at 2-2.5 h after dosing. 3. Xamoterol at all three doses significantly increased exercise duration at 2-2.5 h after dosing but not at 24 h. 4. Mean plasma xamoterol concentration at both 2-2.5 h and 24 h after dosing were dose related. The EC50 for xamoterol is 33.5 ng ml-1, where EC50 is the effective plasma concentration required to produce 50% of the maximum effect on exercise heart rate. PMID- 2889461 TI - The effect of famotidine on renal function in patients with renal insufficiency. AB - The effect of famotidine, a new histamine H2-receptor antagonist, on renal tubular creatinine secretion was evaluated in twelve patients with reduced renal function (creatinine clearance 10-60 ml min-1). Creatinine and inulin clearances were determined at baseline and for 4 h after a 10 mg intravenous dose of famotidine. Famotidine renal clearance exceeded inulin clearance by an average of 152%, indicating that renal tubular secretion of famotidine occurred. No significant changes in the clearances of creatinine or inulin, or the fractional clearance of creatinine were observed after famotidine administration. These data suggest that famotidine, unlike cimetidine, does not inhibit renal tubular secretion of creatinine. Thus, famotidine does not affect creatinine-dependent measurements of renal function and is unlikely to alter the renal elimination of basic drugs. PMID- 2889462 TI - Doppler ultrasound features of stenosis of the aorta in a pregnancy complicated by Takayasu's arteritis. Case report. PMID- 2889463 TI - Maxillofacial and dental soccer injuries in Finland. AB - Between 1979 and 1982 there were 8640 accidents to registered soccer players in Finland. Of these, 552 (6.4%) affected the maxillofacial and dental regions. Medical records were located relating to 537 of these cases (97%). There were a total of 843 injuries, of which 681 (80.8%) affected the teeth or alveolar processes, and 95 (11.2%) were fractures of the lower or middle third of the facial skeleton. The most common cause of the accidents (in 86.4% of cases) was contact with another player. The mean cost of maxillofacial and dental injuries was over twice as high as the mean cost relating to all soccer injuries. The need for the use of mouthguards by soccer players to protect against such injuries is discussed. PMID- 2889464 TI - Epsilon subunit of Escherichia coli F1-ATPase: effects on affinity for aurovertin and inhibition of product release in unisite ATP hydrolysis. AB - The epsilon subunit of Escherichia coli F1-ATPase is a tightly bound but dissociable partial inhibitor of ATPase activity. The effects of epsilon on the enzyme were investigated by comparing the ATPase activity and aurovertin binding properties of the epsilon-depleted F1-ATPase and the epsilon-replete complex. Kinetic data of multisite ATP hydrolysis were analyzed to give the best fit for one, two, or three kinetic components. Each form of F1-ATPase contained a high affinity component, with a Km near 20 microM and a velocity of approximately 1 unit/mg. Each also exhibited a component with a Km in the range of 0.2 mM. The velocity of this component was 25 units/mg for epsilon-depleted ATPase but only 4 units/mg for epsilon-replete enzyme. The epsilon-depleted enzyme also contained a very low affinity component not present in the epsilon-replete enzyme. In unisite hydrolysis studies, epsilon had no effect on the equilibrium between substrate ATP and product ADP.P1 at the active site but reduced the rate of product release 15-fold. These results suggest that epsilon subunit slows a conformational change that is required to reduce the affinity at the active site, allowing dissociation of product. It is suggested that inhibition of multisite hydrolysis by epsilon is also due to a reduced rate of product release. epsilon-depleted F1-ATPase showed little of no modulation of aurovertin fluorescence by added ADP and ATP. Aurovertin fluorescence titrations in buffer containing ethylenediaminetetraacetic acid (EDTA) revealed that epsilon-depleted enzyme had high affinity for aurovertin (Kd less than 0.1 microM) regardless of the presence of nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889465 TI - Acceptor-donor relationships in the transglutaminase-mediated cross-linking of lens beta-crystallin subunits. AB - Following the isolation of the N epsilon-(gamma-glutamyl)lysine-containing polymers from human cataracts, our efforts were directed to induce such cross links experimentally in rabbit lens, and evidence was obtained for the selective reactivities of certain beta-crystallin subunits in this transglutaminase catalyzed event. In the present work, we examined the enzymatic cross-linking of purified crystallins individually (alpha, beta H, beta L, and gamma) and in combinations, with particular emphasis on forming the approximately 55K dimer. This species was the primary product in the cross-linking of beta H-crystallins; beta L also reacted with transglutaminase. Neither alpha- nor gamma-crystallins formed appreciable amounts of cross-linked structures with transglutaminase. Dansylcadaverine, known to compete against the reactive lysines of proteins in forming N epsilon-(gamma-glutamyl)lysine cross-bridges, was shown to inhibit the generation of dimeric and higher ordered oligomers from beta H and beta L. The fluorescent amine specifically labeled only two subunits in beta H (approximately 29-30K and approximately 26K) and one in beta L (approximately 26K), identifying these substrates as possessing transglutaminase-reactive endo-gamma-glutaminyl residues. An antiserum to bovine beta Bp recognized the approximately 23K subunit of rabbit beta-crystallins and also the approximately 55K dimer, suggesting that the approximately 23K protein participates as a lysine donor in generating the cross-linked dimer with transglutaminase. Inasmuch as the same antiserum reacts with an approximately 50K material reported to appear in increasing amounts with age in human lens, the results lend added support to the physiological significance of transglutaminase in the aging of lens. PMID- 2889466 TI - Isolation of products and intermediates of pancreatic prosomatostatin processing: use of fast atom bombardment mass spectrometry as an aid in analysis of prohormone processing. AB - Major products and an intermediate in the proteolytic processing pathway of preprosomatostatin I from anglerfish (Lophius americanus) were purified and characterized. Proteolytic mapping by fast atom bombardment mass spectrometry was used to rapidly locate regions of the peptides whose masses deviated from those deduced from the cDNA sequence. Amino acid analysis and partial Edman sequencing were also used to confirm the structures. The protein structural data indicate a Glu for Gly substitution at position 83 of preprosomatostatin I (aPPSS-I, numbering from the initiator Met) relative to the cDNA sequence. Two of the peptides isolated, aPPSS-I (26-52) (7.5 nmol X g-1) and aPPSS-I (26-92) (49.5 nmol X g-1), define signal cleavage as occurring between Cys-25 and Ser-26. A partial sequence was obtained from fragment ions in the mass spectrum of a peptide corresponding to aPPSS-I (94-105) (58 nmol X g-1). The 14-residue somatostatin [SS-14 corresponding to aPPSS-I (108-121)] has previously been isolated [Noe, B. D., Spiess, J., Rivier, J. E., & Vale, W. (1979) Endocrinology (Baltimore) 105, 1410-1415]. Taken together, these peptides suggest a pathway for prosomatostatin I processing in which the residues corresponding to SS-14 and the immediately preceding 14 residues are cleaved from the prohormone via endoproteolysis (order of cleavage not determined). The fragment aPPSS-I (94-105) was isolated in lower yield than SS-14 and may represent a secondary site of cleavage. Subsequent cleavage at arginine-53 results in the minor peptide aPPSS-I (26-52).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889467 TI - ADP, chloride ion, and metal ion binding to bovine brain glutamine synthetase. AB - The binding of divalent cations and nucleotide to bovine brain glutamine synthetase and their effects on the activity of the enzyme were investigated. In ADP-supported gamma-glutamyl transfer at pH 7.2, kinetic analyses of saturation functions gave [S]0.5 values of approximately 1 microM for Mn2+, approximately 2 mM for Mg2+, 19 nM for ADP.Mn, and 7.2 microM for ADP.Mg. The method of continuous variation applied to the Mn2+-supported reaction indicated that all subunits of the purified enzyme express activity when 1.0 equiv of ADP is bound per subunit. Measurements of equilibrium binding of Mn2+ to the enzyme in the absence and presence of ADP were consistent with each subunit binding free Mn2+ (KA approximately equal to 1.5 X 10(5) M-1) before binding the Mn.ADP complex (KA' approximately equal to 1.1 X 10(6) M-1). The binding of the first Mn2+ or Mg2+ to each subunit produces structural perturbations in the octameric enzyme, as evidenced by UV spectral and tryptophanyl residue fluorescence changes. The enzyme, therefore, has one structural site per subunit for Mn2+ or Mg2+ and a second site per subunit for the metal ion-nucleotide complex, both of which must be filled for activity expression. Chloride binding (KA' approximately equal to 10(4) M-1) to the enzyme was found to have a specific effect on the protein conformation, producing a substantial (30%) quench of tryptophanyl fluorescence and increasing the affinity of the enzyme 2-4-fold for Mg2+ or Mn2+. Arsenate, which activates the gamma-glutamyl transfer activity by binding to an allosteric site, and L-glutamate also cause conformational changes similar to those produced by Cl- binding. Anion binding to allosteric sites and divalent metal ion binding at active sites both produce tryptophanyl residue exposure and tyrosyl residue burial without changing the quaternary enzyme structure. PMID- 2889468 TI - Organization and evolution of the rat tyrosine hydroxylase gene. AB - This report describes the organization of the rat tyrosine hydroxylase (TH) gene and compares its structure with the human phenylalanine hydroxylase gene. Both genes are single copy and contain 13 exons separated by 12 introns. Remarkably, the positions of 10 out of 12 intron/exon boundaries are identical for the two genes. These results support the idea that these hydroxylase genes are members of a gene family which has a common evolutionary origin. We predict that this ancestral gene would have encoded exons similar to those of TH prior to evolutionary drift to other members of this gene family. PMID- 2889469 TI - Effects of some alcohols on the conformation of mitochondrial H+-ATPase complex and F1-ATPase from pig heart. AB - The conformations of the H+-ATPase complex and F1-ATPase in low concentrations of methanol, ethanol, n-propanol, iso-propanol and t-butanol were studied by circular dichroism. For F1-ATPase, all but methanol first increased and then decreased the circular dichroism magnitude of helical bands as the alcohol concentration was increased. With ethanol, n-propanol, iso-propanol and t butanol, the alpha-helix content reached a maximum at about 5% alcohol and began to decrease at 10%. The content of beta-sheet showed the opposite effect, reaching a minimum at 5% and increasing slightly at higher concentrations. None of the alcohols studied had a significant effect on the conformation of the H+ ATPase complex. This difference implies that the alcohols had a greater effect on free F1-ATPase than on the membrane-bound F1-ATPase. The hydrophobic protein F0 and the membrane lipids in the H+-ATPase complex may stabilize and protect F1 from the effects of the alcohols. PMID- 2889470 TI - Thermal inactivation of electron-transport functions and F0F1-ATPase activities. AB - Bovine heart submitochondrial particles in suspension were heated at a designated temperature for 3 min, then cooled for biochemical assays at 30 degrees C. By enzyme activity measurements and polarographic assay of oxygen consumption, it is shown that the thermal denaturation of the respiratory chain takes place in at least four stages and each stage is irreversible. The first stage occurs at 51.0 +/- 1.0 degrees C, with the inactivation of NADH-linked respiration, ATP-driven reverse electron transport, F0F1 catalyzed ATP/Pi exchange, NADH and succinate driven ATP synthesis. The second stage occurs at 56.0 +/- 1.0 degrees C, with the inactivation of succinate-linked proton pumping and respiration. The third stage occurs at 59.0 +/- 1.0 degrees C, with the inactivation of electron transfer from cytochrome c to cytochrome oxidase and ATP-dependent proton pumping. The ATP hydrolysis activity of F0F1 persists to 61.0 +/- 1.0 degrees C. An additional transition, detectable by differential scanning calorimetry, occurring around 70.0 +/- 2.0 degrees C, is probably associated with thermal denaturation of cytochrome c and other stable membrane proteins. In the presence of either mitochondrial matrix fluid or 2 mM mercaptoethanol, all five stages give rise to endothermic effects, with the absorption of approx. 25 J/g protein. Under aerobic conditions, however, the first four transitions become strongly exothermic, and release a total of approx. 105 J/g protein. Solubilized and reconstituted F0F1 vesicles also exhibit different inactivation temperatures for the ATP/Pi exchange, proton pumping and ATP hydrolysis activities. The first two activities are abolished at 49.0 +/- 1.0 degrees C, but the latter at 58.0 +/- 2.0 degrees C. Differential scanning calorimetry also detects biphasic transitions of F0F1, with similar temperatures of denaturation (49.0 and 54.0 degrees C). From these and other results presented in this communication, the following is concluded. (1) A selective inactivation, by the temperature treatment, of various functions of the electron-transport chain and of the F0F1 complex can be done. (2) The ATP synthesis activity of the F0F1 complex involves either a catalytic or a regulation subunit(s) which is not essential for ATP hydrolysis and the proton translocation. This subunit is 10 degrees C less stable than the hydrolytic site. Micromolar ADP stabilizes it from thermal denaturation by 4-5 degrees C, although ADP up to millimolar concentration does not protect the hydrolytic site and the proton-translocation site.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2889471 TI - Circadian rhythms in Neurospora crassa: a clock mutant, prd-1, is altered in membrane fatty acid composition. AB - The fatty acid compositions of the phospholipids of Neurospora crassa mutants with altered periods were determined to test the possibility that some of these mutants might have altered membrane composition. In liquid shaker culture in constant light the bd (band) strain, which has a normal period (21.6 h), exhibited a growth-dependent increase in linoleic acid content and a decrease in linolenic acid content during early log phase growth. By late log phase, fatty acid composition was essentially constant. The phospholipid fatty acid compositions of bd strains containing mutations at the frq (frequency) and chr (chrono) loci were indistinguishable from that of the bd strain under the conditions used. However, a bd strain containing a mutation at the prd-1 (period) locus, as well as prd-1 segregants from a cross of this strain to a bd strain, had altered patterns of growth-dependent fatty acid composition; linoleic and linolenic acid contents changed more slow than in the bd strain and continued to change throughout growth. In addition, the fatty acid composition of a bd prd-1 strain on solid medium differed from that of the bd strain. It is proposed that the prd-1 mutation leads to altered membrane homeostasis, which in turn affects circadian rhythmicity because some or all components of the rhythm-generating system are membrane-localized. PMID- 2889472 TI - Inhibition of erythrocyte transglutaminase by GTP. AB - The guanine nucleotides GTP, GDP and GMP inhibit the activity of erythrocyte transglutaminase (protein-glutamine:amine gamma-glutamyltransferase, EC 2.3.2.13) in a decreasing order of effectiveness. The inhibition is more apparent at low than at saturating levels of calcium ions and is not due to the chelation of Ca2+, but to an interference with the process of activation by the cation. This inhibition is likely to contribute to the latency of erythrocyte transglutaminase in physiological conditions. PMID- 2889473 TI - A simple method for the rapid determination of the stereospecificity of NAD dependent dehydrogenases applied to mammalian IMP dehydrogenase and bacterial NADH peroxidase. AB - The stereospecificity of IMP dehydrogenase (IMP:NAD+ oxidoreductase, EC 1.1.1.205) from two different sources was determined. The enzyme preparations were obtained from murine lymphoblasts and from Escherichia coli. Both enzymes transferred the 2-3H of IMP to the pro-S position of carbon atom C-4 of the nicotinamide ring in NAD. Thus, B-sided stereospecificity is common to the enzyme from two very different species. In addition, the studies described here demonstrate that alcohol dehydrogenase and NADH peroxidase, used as auxiliary enzymes, in combination with a microdistillation procedure, should permit rapid determination of the stereospecificity of any NAD-dependent dehydrogenase for which the appropriate tritiated substrate is available. PMID- 2889474 TI - Inhibition of inosine monophosphate dehydrogenase by sesquiterpene lactones. AB - Inosine monophosphate (IMP) dehydrogenase had previously been determined to be a likely target enzyme for the sesquiterpene lactones, a class of potential anti neoplastic drugs. IMP dehydrogenase was purified approx. 770-fold from the P-388 lymphocytic leukemia tumor cell line. The Km values for the substrates, IMP and NAD, were determined to be 12 microM and 25 microM, respectively. Xanthine monophosphate (XMP) was shown to be a competitive inhibitor with a Ki of 67 microM. Mycophenolic acid gave mixed-type inhibition with a Ki of 8 nM for the noncompetitive component and a Ki of 2 nM for the competitive component. Dissociation constants (Kd) and rate constants for inhibition of IMP dehydrogenase by nine different sesquiterpene lactones were determined. The highest Kd was seen with 2,3-dihydrohelenalin while the lowest Kd was observed with bis-helenalinyl malonate. Binding of the drugs by IMP dehydrogenase increased as the size of the drug increased. Also, changes in structure at position 6 had a relatively large effect on the Kd. There was no correlation with hydrophobicity, as determined by octanol/water partition. The first-order rate constants for the reaction of the sesquiterpene lactones with IMP dehydrogenase (k1) and the second-order rate constants for the reaction of the sesquiterpene lactones with glutathione (k2) were also determined. The rate constants for most of the sesquiterpene lactones with the alpha-methylene-gamma-lactone moiety were similar and were approximately twice as great as the rate constants for those sesquiterpene lactones with only the alpha, beta-unsaturated cyclopentenone ring. Microlenin had approximately 5-times the reactivity of the other sesquiterpene lactones towards IMP dehydrogenase, but had approximately the same reactivity towards glutathione, suggesting that it was bound to the enzyme in a way which facilitated its reaction with one or more essential sulfhydryls. The same procedure was used for a series of N-substituted maleimide compounds with the N substituent ranging in size from a methyl group to a benzyl group. The binding of the maleimide compounds was generally tighter than for the sesquiterpene lactones and there was an increase in binding with size. PMID- 2889475 TI - [The nature of H+-K+-exchange in anaerobically and aerobically grown S. typhimurium]. AB - H+-K+-exchange via the Trk-like system of K+ accumulation takes place in anaerobically grown S. typhimurium LT-2 with stable ratio of DCC-sensitive ionic fluxes, equal to 2H+ of a cell for one K+ of the medium. This exchange is now observed in the mutant S. typhimurium TH-31 with unfunctional H+-ATPase. H+-K+ exchange in aerobically grown S. typhimurium LT-2 has unstable ratio of ionic fluxes. The rate of K+ uptake in anaerobically grown bacteria is higher than that in the aerobically grown ones. Q10 is about 1.8 both for H+ transfer and K+ uptake in anaerobically grown bacteria, but it is 1.7 and 0.9 respectively in the aerobically grown ones. Delta psi is not changed by different temperatures both in anaerobically and aerobically grown bacteria. The distribution of K+ in anaerobically grown bacteria is higher than 10(3) and the potassium equilibrium potential is much higher than the measured delta psi. In aerobically grown bacteria the distribution of K+ is in good conformity with the measured delta psi. H+ and K+ transport in anaerobically grown cells is likely to proceed by the same mechanism, which includes H+-ATPase and the Trk-like system. In aerobically grown bacteria these transport systems work separately, and the Trk-like system as K+-ionophore serving for K+ uptake across the electrical field on the membrane. PMID- 2889476 TI - [Activity of glutathione-dependent enzymes, catalase and superoxide dismutase in the liver and myocardium of rats with vitamin A deficiency]. AB - The alimentary deficiency of vitamin A causes marked shifts in the metabolism of GSH: the levels of GSH, GSSG and cysteine in the liver increase, while the activities of glutathione-S-transferase (using glycerol as substrate) and gamma glutamyltransferase in the liver show a rise. At the same time, vitamin A deficiency causes a decrease of the glutathione peroxidase and catalase activity in the liver. The data obtained are discussed in terms of the role of GSH and enzymes of GSH metabolism in the protection of cells against the damaging influence of lipid peroxidation. PMID- 2889477 TI - [Guanylate cyclase from human blood platelets]. AB - Human blood platelets were disrupted by ultrasonication, and the guanylate cyclase activity was determined in the 105,000 g supernatant. The guanylate cyclase preparation obtained in the absence of dithiothreitol (DTT) was characterized by a nonlinear dynamics of cGMP synthesis during incubation at 37 degrees C. The use of 0.2 mM DTT during platelet ultrasonication stabilized the guanylate cyclase reaction and did not influence the enzyme activity. With a rise in DTT concentration up to 2 mM the guanylate cyclase activity diminished. Sodium nitroprusside stimulated the enzyme; this effect was enhanced in the presence of DTT. The maximum guanylate cyclase activity was revealed at 4 mM Mn2+ or Mg2+ and with 1 mM GTP. In the presence of Mn2+ the enzyme activity was higher than with Mg2+. The apparent Km values for GTP in the presence of 4 mM Mn2+ and Mg2+ was 30 and 200 microM, respectively. At GTP/cation ratio of 1:4 the Km values for Mn2+ and Mg2+ were nearly the same (249 and 208 microM, respectively). It was assumed that besides being involved in the formation of the GTP-substrate complex, Mn2+ exerts a strong influence on guanylate cyclase by oxidizing the SH-groups of the enzyme. PMID- 2889478 TI - Visuomotor performance of schizophrenic patients and normal controls in a picture viewing task. AB - The eye movements of 20 partially remitted schizophrenic outpatients (ICD-9) under neuroleptic maintenance medication and those of 20 normal controls were recorded using corneal reflection pupil-center measurement. The visuomotor performance during a 1-min picture viewing task was studied on the basis of several eye movement parameters. Clinical evaluation comprised self-ratings (Frankfort Complaint Questionnaire) and observer ratings (BPRS, CGI, GAS), as well as recording of current daily neuroleptic dosage (mg CPZ). The main results are that schizophrenics differ from normals in their correlational pattern of fixation- and movement-related parameters, reflecting two opposite viewing styles in schizophrenics: staring and extensive scanning. Both styles are differently related to clinical symptomatology. There was no strongly marked relationship with neuroleptic dosage. PMID- 2889479 TI - Smoking and tardive dyskinesia. PMID- 2889480 TI - Sequence analysis of a cDNA clone encoding the C-terminal end of human complement factor H. AB - Peptide sequencing of the complement system regulatory protein, factor H, permitted the synthesis of a mixed sequence oligonucleotide probe. Human liver cDNA libraries were screened and factor H-specific clones selected. No full length clone was obtained, but the largest available clone, R2a, was found to encode the C-terminal 657 amino acids of factor H. The derived amino acid sequence consists of 10 contiguous internally homologous segments, each about 60 amino acids long. Sequences homologous to these are found in several other complement and non-complement proteins. Such sequences are likely to represent a particular type of tertiary structure subunit. PMID- 2889482 TI - [Role of the locus coeruleus in the mechanism of different types of analgesia]. AB - The activity of antinociceptive mechanisms during exposure to cold swim stress (CSS), inescapable foot shock (FS) and morphine administration (10 mg/kg) was studied in rats subjected to bilateral lesions of locus coeruleus (LC). It has been shown that under all types of stimulation the latent periods (LP) of nociceptive reactions of paw licking and tail flick were significantly increased, as compared to baseline level, thus suggesting suppression of the pain sensitivity. In rats subjected to CSS and morphine administration significantly shorter LP were revealed in the experimental group, compared to the control, which suggested partial inhibition of antinociceptive mechanisms activity after LC lesion. FS did not cause any differences in the experimental and control groups. It is concluded that LC lesions cannot completely inhibit the antinociceptive mechanisms activated by CSS and morphine injection. In FS monoamine mechanisms of LC do not seem to play an important role in the functioning of antinociceptive mechanisms. PMID- 2889481 TI - [A new principle in the analysis of the analgesic action of morphine]. AB - Possible application of sensory decision theory of pain for the experimental assessment of neuropsychophysiological mechanisms of opiate analgesia has been demonstrated. The analgetic effect of morphine was found to be mediated through the influence on the measurement and estimation of pain stimulus. PMID- 2889483 TI - Molecular characterization of chromosome 7 long arm deletions in myeloid disorders. AB - Partial deletion of the long arm of chromosome 7 is a common abnormality in the bone marrow cells of patients with myelodysplastic syndrome (MDS) or acute nonlymphocytic leukemia (ANLL). This study was undertaken to characterize the chromosome breakpoints in molecular terms and to determine if hemizygosity or submicroscopic deletions occur in patients without any cytogenetically detectable abnormality of chromosome 7. We studied restriction fragment length polymorphisms with 10 chromosome 7-specific DNA probes in separated WBC fractions. No molecular abnormalities occurred in lymphocyte-derived DNA. Several probes located in band 7q22 or distally thereof detected deletion of one allele in granulocyte-derived DNA from all four patients with chromosome 7 long arm deletion. In the granulocytes of one patient heterozygosity for the T cell receptor beta chain gene (in band 7q35) indicated that the deletion was interstitial. NJ-3, a proalpha2(I)collagen gene probe (in band 7q21-22) detected heterozygosity in the granulocytes of one patient. No hemizygosity or deletions were found in four patients with two normal chromosomes 7. These results confirm that mature granulocytes but not lymphocytes are derived from the abnormal clone. Interstitial deletions exist, and the extent of deleted genomic material varies among patients. PMID- 2889484 TI - Evidence for the interleukin-2 dependent expansion of leukemic cells in adult T cell leukemia. AB - Interleukin 2 (IL-2) receptor/Tac antigen is abnormally expressed on cells of patients with adult T cell leukemia (ATL) caused by infection with human T lymphotropic virus type I (HTLV-I). Twenty-five patients with ATL were examined to determine whether their leukemic cells continued to show IL-2-dependent proliferation. In 21 patients, the in vitro proliferation of HTLV-I-infected nonleukemic T cell clones was found to be dependent on IL-2. However, clonality analysis based on T cell receptor gene rearrangement profiles and the site of HTLV-I provirus integration revealed IL-2-dependent growth in leukemic cells in four patients with ATL. These results provide evidence for the IL-2-dependent proliferation of leukemic cells in some ATL patients. PMID- 2889485 TI - Correlation of chromosome abnormalities with histologic and immunologic characteristics in non-Hodgkin's lymphoma and adult T cell leukemia-lymphoma. Fifth International Workshop on Chromosomes in Leukemia-Lymphoma. AB - To correlate cytogenetic findings with histology and immunophenotype, 260 newly diagnosed patients with non-Hodgkin's lymphoma (NHL) and 31 with adult T cell leukemia/lymphoma (ATL) were studied at the Fifth International Workshop on Chromosomes in Leukemia-Lymphoma. Clonal chromosome abnormalities were found in 85% of cases of NHL and in all cases of ATL. The most significant associations of histology with cytogenetics involved the 8q24 and 14;18 translocations. Of 23 NHL patients with an 8q24 translocation, 20 (87%) had small noncleaved cell (SNC) lymphoma. Of 57 NHL patients with a t(14;18)(q32;q21), 37 (65%) had a follicular lymphoma, and at least 13 others (23%) had a diffuse lymphoma of follicular center cell origin. Five others including two who also had an 8q24 translocation had SNC lymphoma; tumors in these patients lacked the monomorphic features seen in those with only an 8q24 translocation. The most striking associations of immunology with cytogenetics involved rearrangements of 14q11-13, abnormalities of 1p, trisomy 3, and trisomy 12. Abnormalities of 14q11-13 were correlated with T cell disease. Among 138 NHL and 24 ATL cases that lacked involvement of 8q24, t(14;18), or rearrangements of 14q11-13, abnormalities of 1p and trisomy 3 were significantly associated with the T cell phenotype (P less than .01) and trisomy 12 with the B cell phenotype (P less than .01). No karyotype difference was found between Japanese ATL and non-Japanese T cell lymphomas except that +3 occurred more often in the former (P = .06). Although the 8q24 translocations in 23 patients were distributed relatively equally among geographic regions (United States, ten; Europe, ten; Japan, three), the t(14;18) in 57 patients was much less frequently seen in Japan than in the other parts of the world (United States, 31; Europe, 21; Australia, four; Japan, one). Thirty-nine chromosome bands had breaks in five or more cases; a number of protooncogenes and genes related to lymphocyte function located in these bands are likely to be involved in the development of lymphoma. Thus, besides confirming the close association of particular chromosome abnormalities with histology, we have identified a number of new associations that merit molecular analysis. PMID- 2889486 TI - Localization of a collagen-interactive domain of human von Willebrand factor between amino acid residues Gly 911 and Glu 1,365. AB - A collagen-binding domain of von Willebrand factor (vWF) has been identified in the central part of the molecule by comparing the binding properties of vWF and Staphylococcus aureus V-8 protease-generated vWF fragments with collagen. The binding of purified human vWF to human type III collagen was found to be specific. At saturation, 38 to 50.2 micrograms of vWF bound per milligram of collagen. Scatchard plots derived from binding isotherms demonstrated the presence of at least two classes of binding sites. Purified vWF was digested with S aureus V-8 protease into two complementary fragments (SpIII and SpII). SpII, the C-terminal end of vWF (amino acid residues 1,366 to 2,050), was totally devoid of affinity for collagen. Contrarily, purified SpIII, the N-terminal part of vWF (residues 1 to 1,365), totally displaced vWF binding and specifically bound to collagen. At saturation, 25 to 45 micrograms of SpIII bound per milligram of collagen. Scatchard plots demonstrated the presence of a single class of binding sites. SpIII was further digested with the same enzyme to generate SpI, a 52-kilodalton fragment from the C-terminal part of SpIII (residues 911 to 1,365). Spl induced a dose-dependent inhibition of both vWF and SpIII binding to collagen. A series of six monoclonal antibodies against SpIII that completely abolished vWF and SpIII interaction with collagen also bound to SpI. In conclusion, SpI extending between amino acid residues 911 and 1,365 of vWF contains a specific site that interacts with human type III collagen. PMID- 2889487 TI - A model for experimental asthma: provocation in guinea-pigs immunized with Bordetella pertussis. AB - Guinea-pigs were sensitized with killed Bordetella pertussis (3.85 X 10(11) cells . kg-1). The presence of the immediate type of immune response was verified by passive cutaneous anaphylaxis (PCA). In anaesthetized spontaneously-breathing guinea-pigs respiration rate, tidal volume, minute ventilation, dynamic lung resistance and dynamic lung elastance were estimated on the basis of airflow velocity and pressure in the oesophagus. After provocation by a single intravenous injection of the killed cells, respiratory frequency, elastance and resistance increased but tidal volume decreased. The preventive effects of aminophylline and clemastine (50 microns . kg-1, i.v.) were observed. B. pertussis not only alters adrenergic function but provocation in B. pertussis sensitized guinea-pigs seems to be a good model for bronchial asthma. PMID- 2889488 TI - The beta-adrenoceptors of lymphocytes in asthmatic patients treated with beta agonists. AB - Numbers of beta-adrenoceptors in intact human lymphocytes of asthmatics treated continuously with the usual doses of beta-agonists have been estimated. Lymphocytes were isolated by density gradient centrifugation as described by BOYUM [4]. The binding experiment was performed with (-)3H-dihydroalprenolol which is a high affinity beta-adrenoceptor antagonist. There was no difference between the mean values of the binding sites of asthmatic patients and those of the normal volunteers. In asthmatic patients, a significant correlation was found between the density of receptors and the percentage increase of FEV1 after salbutamol inhalation. Symptoms of drug tolerance were not observed in patients treated with therapeutic doses of beta-agonists. PMID- 2889489 TI - Mechanical and electrical responses to alpha-adrenoceptor activation in the circular muscle of guinea-pig stomach. AB - 1 In the circular muscle of the corpus region of the guinea-pig stomach, the effects of catecholamines on mechanical activity were studied with simultaneous recording of membrane potential by use of intracellular microelectrodes. In order to investigate responses mediated through alpha-adrenoceptors, the beta adrenoceptors were blocked by propranolol (10(-6) M) in most experiments. 2 Adrenaline (less than 10(-6) M) produced a monophasic contraction with little change in membrane potential. At higher concentrations (greater than 10(-5) M), adrenaline usually produced an early transient contraction followed by a slow tonic contraction. During the early phase, the membrane was hyperpolarized and slow waves were reduced in amplitude. 3 The phasic contractions superimposed on the late slow phase of the contractile response were higher in frequency and larger in amplitude than in controls before adrenaline application. These changes were associated with an increase in the amplitude and frequency of slow waves, and with a spike-like component appearing on the top of each slow wave. 4 Adrenaline-induced changes in mechanical and electrical activity were inhibited by prazosin, but largely unaffected by yohimbine. In some preparations, there was a transient weak inhibition of phasic contraction before muscle tone was increased by adrenaline, and this became more pronounced in the presence of yohimbine. 5 Phenylephrine, selective for alpha 1-receptors, produced responses very similar to those of adrenaline, whereas agonists selective for alpha 2 receptors, clonidine and B-HT 920, produced only a small slow contraction without any clear change in membrane potential. 6 It is concluded that in the circular muscle of guinea-pig stomach, the contractile response and changes in the electrical slow wave activity produced by adrenaline are both mediated mainly through the activation of alpha-receptors. PMID- 2889490 TI - The expression of N-methyl-D-aspartate-receptor-mediated component during epileptiform synaptic activity in hippocampus. AB - 1 The possible involvement of N-methyl-D-aspartate (NMDA)-receptors in epileptiform synaptic activity in the kainic acid (KA) lesioned hippocampus was investigated. In this chronic model of epilepsy there is a loss of both the early and the late components of synaptic inhibition as well as changes in the membrane properties of the surviving CA1 pyramidal cells. 2 The action of the specific NMDA-receptor antagonist D-2-amino-5-phosphonovalerate (D-APV) was tested on evoked bursts of action potentials recorded intracellularly from cells of lesioned hippocampi. The effects of D-APV on control synaptic responses from the contralateral, unlesioned hippocampi were also recorded. 3 In the presence of Mg2+ (1 mM), D-APV (20 microM) had a profound effect on the evoked epileptiform activity. Both the number of action potentials in the burst, as well as the area under the excitatory postsynaptic potential (e.p.s.p.) was considerably reduced. Furthermore this D-APV-sensitive component of the epileptiform burst had a very early onset, coincident with the first action potential in the burst. 4 D-APV (20 microM) was ineffective in blocking the e.p.s.p. evoked by Schaffer collateral afferents onto CA1 cells in slices of hippocampus contralateral to the KA lesion. 5 D-APV had no effect on the passive membrane properties of either population of cells. Hyperpolarizing potentials such as the inhibitory postsynaptic potentials (i.p.s.ps) or the afterhyperpolarization following a current-induced burst of action potentials were also unaffected. 6 It appears that an NMDA-receptor component is expressed during synaptically evoked epileptiform activity in this chronic model of epilepsy. PMID- 2889491 TI - Postjunctional alpha 2-adrenoceptors mediate venoconstriction in the hindquarters circulation of anaesthetized cats. AB - 1 A study was made of the subtypes of postjunctional alpha-adrenoceptors which mediate arterial and venous constriction in the hindquarters circulation of anaesthetized cats, as measured by changes in perfusion pressure and vena cava blood flow, respectively. 2 It was found that, while noradrenaline caused constriction in both the arterial and venous compartments, methoxamine caused only arterial constriction. Clonidine and B-HT 920 also caused arterial and venous constriction although autodesensitization to both drugs occurred. 3 The ability of either prazosin or yohimbine to antagonize the constrictor effects of noradrenaline was also examined. It was found that the combination of both antagonist drugs abolished both the arterial and venous constrictor effects of noradrenaline. However, there was a greater prazosin-resistant response to noradrenaline in the venous compartment as compared with the arterial effects of noradrenaline. Yohimbine caused approximately equal reductions in the effect of noradrenaline in both arteries and veins, which was greater than that observed with prazosin. 4 These results suggest that, in the cat hindquarters, both alpha 1- and alpha 2-adrenoceptors are present in the arterial circulation, whereas there are mainly alpha 2-adrenoceptors in the venous circulation. PMID- 2889493 TI - Alpha 2-adrenoceptor blockade prevents cardiac glycoside-evoked neurotransmitter release from sympathetic nerves in dog saphenous vein. AB - 1 The effect of alpha-adrenoceptor antagonists upon neurotransmitter release evoked by cardiac glycosides from sympathetic nerve terminals has been investigated in dog saphenous vein. 2 In rings of saphenous vein preloaded with [3H]-noradrenaline, acetylstrophanthidin (ACS) caused a concentration-dependent efflux of 3H (EC50 ca. 4.4 microM) that was attenuated by phentolamine and yohimbine but not by prazosin. 3 In helical strips of saphenous vein superfused with ACS at EC50 the efflux of 3H-compounds in general, and of [3H]-noradrenaline in particular, occurred after a short delay and increased with time to a maximum reached at 75 min. Phentolamine and phenoxybenzamine, but not prazosin reduced the efflux of [3H]-noradrenaline and of total 3H-compounds throughout the time course of the ACS-evoked effect. 4 In helical strips of saphenous vein the glycoside ouabain also caused an increase in [3H]-noradrenaline and in total 3H efflux that was attenuated by phentolamine. 5 By contrast with the above, in bovine adrenal medullary chromaffin cells, which appear to have no functional alpha-adrenoceptors, ACS caused a small, but significant increase in 3H-efflux which was not prevented by phentolamine. 6 Phentolamine, at concentrations that attenuate markedly the ouabain- or ACS-evoked increase in 3H-efflux from dog saphenous vein, did not cause significant inhibition of cocaine-sensitive [3H] noradrenaline uptake nor did it reduce the extent of the 3H-efflux evoked either by tyramine or by reduced extracellular Na+. These findings imply that phentolamine does not affect ACS-evoked neurotransmitter release by an action on the catecholamine uptake mechanism. 7. It is concluded that the cardiac glycoside evoked increase in neurotransmitter release from noradrenergic nerve terminals ofdog saphenous vein is modulated by a mechanism that involves an alpha2- adrenoceptor. PMID- 2889492 TI - Antisecretory and antiulcer effect of the H2-receptor antagonist famotidine in the rat: comparison with ranitidine. AB - 1 The effects of the new H2-receptor antagonist famotidine, administered orally, on gastric secretion and emptying as well as on experimentally-induced gastric and duodenal ulcers were studied in the rat. Ranitidine was used as a reference compound. 2 Both compounds inhibited acid secretion in a dose-dependent manner. Calculated ED50 values were 0.80 and 6.84 mg kg-1 for famotidine and ranitidine, respectively. However, the duration of the antisecretory action was the same for both drugs. 3 The effect of the two drugs, administered at equiactive antisecretory doses, on gastric emptying was different. Ranitidine significantly accelerated the emptying rate whereas famotidine had no effect. 4 Famotidine reduced, in a dose-dependent manner, ulcer incidence in stomachs of dimaprit treated rats and in duodena of cysteamine-treated animals with a potency respectively 2 and 7 times higher than that of ranitidine. 5 Famotidine is therefore an effective antisecretory and untiulcer compound. Its potency, but not its efficacy, is higher than that of ranitidine. Moreover, the duration of the antisecretory action is virtually the same for both drugs. PMID- 2889495 TI - The Scottish First Episode Schizophrenia Study. II. Treatment: pimozide versus flupenthixol. The Scottish Schizophrenia Research Group. AB - In a randomised double-blind study, 46 first episode schizophrenics were given pimozide or flupenthixol for up to 5 weeks; the mean daily dose at the end was 18.8 mg pimozide and 20 mg flupenthixol. There were no significant between-drug differences in the effect on mental state or behaviour; positive schizophrenic symptoms responded to treatment, negative symptoms did not. Most patients required anti-Parkinsonian medication. Poor response was associated with 'organicity'. A switch to maintenance therapy after 5 weeks, the outcome of successful treatment and patient cooperation, was achieved in only 54%. There was no relationship between plasma prolactin levels and severity of schizophrenic symptoms in unmedicated patients. Pimozide produced greater elevation of plasma prolactin. Plasma neuroleptic levels showed drug compliance was satisfactory throughout in only 54%. PMID- 2889496 TI - A case of resistant schizophrenia. PMID- 2889494 TI - The protective effects of sulphasalazine against ethanol-induced gastric damage in rats. AB - 1 The inhibitory action of sulphasalazine on ethanol-induced gastric damage was studied in rats. 2 Sulphasalazine (62.5 or 125 mg kg-1, s.c.) did not affect basal gastric acid secretion but increased pepsin output. 3 Ethanol (40% v/v, 10 ml kg-1, p.o.) produced severe gastric glandular mucosal damage and lessened the stomach emptying rate of resin pellets, but it increased the levels of prostaglandin E2 (PGE2)-like activity in the glandular mucosa. 4 Sulphasalazine markedly prevented ethanol-induced damage and significantly elevated gastric wall mucus levels both in basal conditions and in the presence of ethanol. 5 Sulphasalazine caused a small insignificant increase in mucosal PGE2 levels in both control and ethanol-treated rats. The drug significantly increased mucosal PGE2 levels in indomethacin-treated animals, but did not prevent indomethacin induced mucosal damage. 6 Sulphapyridine but not 5-aminosalicylic acid, constituents of sulphasalazine, showed a similar antilesion action to the parent drug, and prevented gastric wall mucus depletion in ethanol-treated animals. 7 This study elucidates the protective effects of sulphasalazine against ethanol induced gastric lesions. The antagonistic action appears to be mediated, at least partly, through the preservation of gastric wall mucus by sulphapyridine. PMID- 2889497 TI - A case of resistant schizophrenia. PMID- 2889498 TI - Gamma glutamyl transpeptidase and mean cell volume in alcoholics. PMID- 2889499 TI - HLA-B27 related arthritis, sulphasalazine and rheumatoid arthritis. PMID- 2889500 TI - Comparison of faecal florae in patients with rheumatoid arthritis and controls. AB - The faecal flora of 25 out-patients with active rheumatoid arthritis (RA) was compared with that of 25 age- and sex-matched controls. A comprehensive survey revealed a significantly higher carriage rate of Clostridium perfringens in the RA population (88%) than controls (48%) (p less than 0.01). Coliform counts also tended to be higher, but there were no other significant differences between patients and controls. When the study was enlarged to include a further 113 RA patients with variable disease activity and a further 38 controls, clostridia were again more frequently carried by those with RA (70%) than controls (45%) (p less than 0.01) and clostridial counts were significantly higher in the patient group (p = 0.006). Moreover, counts in patients with active or moderately active disease were significantly higher than in those with inactive disease (p less than 0.001). These data are consistent with the hypothesis that Cl. perfringens plays a role in triggering or is otherwise associated with disease activity in RA. The findings may be alternatively an effect of the disease or its treatment with, for example, anti-inflammatory drugs. PMID- 2889501 TI - Effects of sulphasalazine on faecal flora in patients with rheumatoid arthritis: a comparison with penicillamine. AB - Twenty-six out-patients with active rheumatoid arthritis (RA) were randomly allocated to treatment with sulphasalazine (SASP) or D-penicillamine (DPA). Faecal samples were collected from all patients at 4-weekly intervals and examined for changes in faecal flora during treatment. Both treatment groups showed substantial clinical improvement. In the SASP-treated group this was accompanied by significant falls in counts of Cl. perfringens and E. coli. No such changes were seen in the DPA-treated group. These results suggest that SASP's efficacy in RA may be related to its antibacterial properties. PMID- 2889502 TI - The ascending testis--anatomical obstruction to descent at orchiopexy. PMID- 2889503 TI - Effect of the pre-operative response to H2 receptor antagonists on the outcome of highly selective vagotomy for duodenal ulcer. AB - From 1979 to 1984, 141 consecutive patients (110 men, 31 women) underwent highly selective vagotomy (HSV) for duodenal ulcer (DU). All patients had received pre operative treatment with full dose H2 receptor antagonists (H2RA). Indications for surgery were: persistent relapse on withdrawal of H2RA, 107 (75.9 per cent); no response to H2RA, 30 (21.3 per cent); intolerance of H2RA, 1 (0.7 per cent); acute DU bleed, 2 (1.4 per cent); duodenal stenosis, 1 (0.7 per cent). Follow-up with a median of 47 months (24-85 months) revealed six patients (4.4 per cent) with endoscopically proven recurrence, three of whom were on non-steroidal anti inflammatory drugs (NSAIDs). Only one patient with recurrent DU was a non responder to H2RA pre-operatively. Twenty-five patients remained symptomatic after HSV without ulcer recurrence, of which a highly significant proportion (41 per cent) were non-responders (P less than 0.001). The pre-operative response to H2RA does not indicate the likelihood of ulcer recurrence after HSV. However, non responders are more likely to continue with dyspeptic symptoms despite the successful healing of their ulcers. The DU recurrence rate in patients taking long-term NSAIDs is disappointingly high (33 per cent), putting the use of HSV in these patients into question. PMID- 2889504 TI - Psoriasis as a side effect of beta blockers. PMID- 2889505 TI - Regular review: somatostatin. PMID- 2889506 TI - Acute stress erosions: can they be prevented? PMID- 2889507 TI - Impact of molecular biology on clinical genetics. PMID- 2889508 TI - Cardiovascular responses elicited by stimulation of neurons in the central amygdaloid nucleus in awake but not anesthetized rats resemble conditioned emotional responses. AB - Cardiovascular responses elicited by electrical stimulation of the central amygdaloid nucleus were examined in awake and anesthetized rats. Stimulation through chronically implanted electrodes evoked increases in arterial pressure and heart rate in awake, freely behaving rats. The responses, which were dependent upon the frequency and the intensity of the stimulus, were not consistently related to the presence of evoked amygdaloid afterdischarges or to evoked behavioral reactions. Following induction of anesthesia, stimuli delivered to the same rats through the same fixed electrodes produced decreases in blood pressure and heart rate. Microinjection of L-glutamate into the amygdala of freely behaving rats also elicited increases in arterial pressure and heart rate, indicating that the cardiovascular changes evoked by electrical stimuli are due to excitation of local neurons rather than fibers of passage. The timing and pattern of the response elicited by electrical stimulation of the amygdala in the awake but not the anesthetized rat closely corresponds with that evoked by an acoustic conditioned emotional stimulus. PMID- 2889509 TI - Molecular action mechanism of spider toxin on glutamate receptor: role of 2,4 dihydroxyphenylacetic acid in toxin molecule. AB - Joro spider toxin (JSTX) isolated from Nephila clavata was shown to inhibit L glutamate binding to rat brain synaptic membranes in a dose-dependent manner. 2,4 Dihydroxyphenylacetic acid (2,4-DHPA), a common moiety of spider toxins, also inhibited specifically L-glutamate binding at a concentration similar to that of the toxin. The binding activity inhibited by 2,4-DHPA or JSTX was recoverable on addition of ferric compound. These results suggest that 2,4-DHPA is a functional moiety in the toxin molecule and the biological action of spider toxin is explained by direct interaction with an Fe-S center which is known to play an important role for the glutamate binding. PMID- 2889510 TI - Modulation of the excitability of septohippocampal terminals in the rat: relation to neuronal discharge rate. AB - The excitability of the axonal terminals of medial septal neurons projecting to the dentate gyrus has been studied in the anesthetized rat under various experimental conditions: spontaneous or drug-induced variations in neuronal soma discharge rate, conditioning stimulation of afferent pathways (perforant path, commissural pathway, fimbria-fornix). It has been observed that terminals excitability is inversely correlated to the level of neuronal ongoing activity. These effects were observed on virtually all septal neurons projecting to the dentate gyrus. Since about one half of the septohippocampal neurons are likely to be cholinergic, it follows that such a phenomenon is not transmitter specific. PMID- 2889511 TI - Histamine sensitive sites in hippocampus: their probable role on prolactin release in male rats. AB - The effect of histamine (HA), 3-methyl-histamine (3MHA), HA antagonists or drugs interfering with HA synthesis, microinjected into the hippocampus (HPC), on prolactin (PRL) secretion were studied in rats. Three experiments were performed. In Experiment 1, increasing doses of HA or 3-MHA (9-90 nmol) were microinjected stereotaxically into the ventral HPC of adult male rats. In Experiment 2, 135 nmol of pyrilamine (PYR, an H1-HA-antagonist) or ranitidine (RAN, an H2-HA antagonist) were administered locally into the ventral HPC. Fifteen min later, the rats were microinjected again with 45 nmol of HA. In Experiment 3, rats were microinjected with different doses of HA-antagonists or with 20 nmol of alpha fluormethyl-histidine (FMH, an inhibitor of the enzyme of HA synthesis) and later subjected to an immobilization stress of 15 min duration. In all cases, the PRL plasma concentrations were measured in blood samples taken at different time intervals (0-120 min) after the last brain injection. Results showed that HA applied locally in ventral HPC induced an increase in PRL levels which was statistically significant from saline-injected rats between 5-30 min after the HPC stimulation. On the contrary, local applications of 3-MHA did not change significantly the PRL blood levels (Experiment 1). Only PYR did block partially the PRL response due to HA in basal conditions. RAN in these later conditions had no effect (Experiment 2). When animals were subjected to stress neither PYR nor RAN, alone or in combination, locally applied were able to block the PRL increase due to stress. Only FMH blunted significantly the hormone response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889512 TI - Rostral hypothalamus: a new neuroanatomical site of neurochemically-induced emesis in the cat. AB - The localized effect of noradrenergic agonists administered directly in the anterior hypothalamic preoptic area (AH/POA) in inducing emesis in the cat was investigated. Of the noradrenergic agonists tested, which included norepinephrine, clonidine, phenylephrine and methoxamine, only clonidine in doses of 5.0-50.0 micrograms was found to evoke emesis consistently when micro-injected in a volume of 1.0 microliter into AH/POA of the unrestrained cat. The emetic response to clonidine was short-lasting, generally dose-dependent in terms of latency and frequency, and occurred in bouts of one to three episodes. The sequence of the vomiting response, beginning with licking and retching, functionally resembled a normal pattern of an emetic response. The clonidine induced emesis was not antagonized by the following antagonists micro-injected in AH/POA just prior to clonidine: alpha-adrenergic blocking agents, yohimbine, RX 781094 and phentolamine; the antimuscarinic drug, atropine; the serotonin antagonist, methysergide; the opioid antagonist, naloxone; and the dopamine antagonist, chlorpromazine. Therefore, it would appear that clonidine-induced emesis is not mediated by alpha noradrenergic, serotonergic, dopaminergic, muscarinic and opiate receptor systems within the AH/POA of the cat. Finally, the obtained results show that apart from the area postrema and a circumscribed zone of the brain-stem reticular formation, the hypothalamus is now implicated as a neuroanatomical site in the central nervous system mechanism underlying neurochemically-induced emesis. PMID- 2889513 TI - [Results of virology research in organic and functional psychoses]. PMID- 2889514 TI - 'The fire coral' (Millepora dichotoma) as a cause of burns: a case report. AB - A case of a full skin thickness burn after contact with a Hydrozoa, Millepora dichotoma, is described. The poison secreted by specialized cells on the spines of this marine animal is a strong local irritant. Deep burns due to this agent do not appear to have been described before. PMID- 2889515 TI - An overview of the human interleukin-2 receptor: molecular, biochemical, and functional properties. PMID- 2889516 TI - Comparative effects of rauwolscine, prazosin, and phentolamine on blood pressure and cardiac output in anesthetized rats. AB - The endogenous role of the alpha-adrenergic system in the maintenance of mean arterial pressure (MAP), total peripheral resistance (TPR), cardiac output (CO) and its distribution, and plasma norepinephrine and epinephrine release was investigated by the administration of selective alpha-adrenoceptor antagonists to halothane-anesthetized rats. The blockade of alpha 1-, alpha 2-, and both alpha 1 and alpha 2-receptors was accomplished by i.v. infusions of prazosin, rauwolscine, and phentolamine, respectively. The microsphere technique was used for the determination of CO and its distribution. Since the infusions of the three antagonists caused similar decreases of MAP and heart rate, the results suggest that postjunctional alpha 1- and alpha 2-receptors are both important in the control of MAP. During the infusion of prazosin, TPR was decreased but CO was not changed. In contrast, CO was decreased but TPR was not changed during the infusions of rauwolscine and phentolamine. Thus, CO was reduced after the blockade of alpha 2- but not alpha 1-receptors. All three antagonists caused an increase in percent distribution of CO to the lungs and muscle, suggesting that the sympathetic nervous system plays the greatest vasoconstrictor influence in the lungs and muscle via stimulations of both subtypes of alpha-adrenoceptors. The administration of either prazosin or rauwolscine caused little change in plasma catecholamine levels. In contrast, phentolamine caused large increases in both epinephrine and norepinephrine levels. Therefore catecholamine release was only increased after concurrent blockade of both alpha 1- and alpha 2 adrenoceptors. PMID- 2889518 TI - A randomized controlled trial of amantadine in fatigue associated with multiple sclerosis. The Canadian MS Research Group. AB - One hundred and fifteen patients with definite multiple sclerosis (M.S.) and chronic persistent fatigue were studied. This ten-week cross-over study consisted of a 2-week baseline period and two 3-week treatment periods separated by a 2 week washout. Patients received either amantadine 100 mg bid or matching placebo capsules. Fatigue, the effect of fatigue on an individually pre-selected activity and its effect on activities of daily living, were evaluated. Amantadine produced a small but statistically significant decrease in fatigue. An important placebo effect was noted. Mean fatigue during the washout period was lower than during the placebo run-in period, independently of which treatment had been given first. Side effects were numerous both on amantadine and on placebo. Only insomnia was significantly more common with amantadine. PMID- 2889517 TI - Stereospecific binding of a new benzazepine, [3H]SCH23390, in cortex and neostriatum. AB - The binding of the D1 antagonist SCH23390 to membrane preparations from rat cerebral cortex was examined using enantiomers of dopamine agonists and antagonists to compete with the bound [3H]SCH23390 at its Kd value. The competition curves were compared with those obtained with preparations from the neostriatum. The results demonstrate that specific [3H]SCH23390 binding in the cerebral cortex has the same pharmacological profile as in the neostriatum, so that this radioligand can be used to label dopamine D1 receptors in brain regions with a sparse dopaminergic innervation. PMID- 2889519 TI - "Seabather's eruption". PMID- 2889520 TI - Local and systemic reactions from jellyfish stings. PMID- 2889521 TI - Coelenterate (cnidarian) stings and wounds. PMID- 2889522 TI - Immunotherapy using the streptococcal preparation OK-432 for the treatment of uterine cervical cancer. Cervical Cancer Immunotherapy Study Group. AB - The effectiveness of immunotherapy using a streptococcal preparation, OK-432, was evaluated for cervical cancer. The 382 eligible patients were stratified by presence/absence of surgical operation and clinical stage, and then, in each stratum, were randomly divided into two groups: an OK-432 treatment group and a control treatment group. The 3-year recurrence-free rates of 221 patients in the OK-432 group and 161 patients in the control group were 71.9% and 58.6%, respectively. The intergroup difference was statistically significant (P less than 0.05). Delayed skin reactions to phytohemagglutinin (PHA) and Su polysaccharide extracted from Streptococcus pyogenes Su-strain (Su-PS) and peripheral lymphocyte counts were reduced within two months after the initiation of therapy in both groups. The observed immunological changes were apparently reversed by 3 months after the start of the therapy in the OK-432 group, but this took at least one year in the control group, with significant intergroup differences at 6 and 12 months of the therapy (P less than 0.01). These results indicate that OK-432 can be considered as one of the most effective and useful immunotherapeutic agents for cervical cancer. PMID- 2889523 TI - Analysis of 13q RFLP in multiple endocrine neoplasia type II kindreds. PMID- 2889524 TI - Genetics of cancer predisposition. PMID- 2889525 TI - Inability of mitogen-induced liver hyperplasia to support the induction of enzyme altered islands induced by liver carcinogens. AB - Experiments were designed to determine whether liver cell proliferation induced by direct mitogens is as effective as compensatory cell proliferation consequent to previous cell loss, in supporting the growth of enzyme-altered islands in the liver induced by chemical carcinogens. Male Wistar rats were given injections of a single nonnecrogenic dose of N-methyl-N-nitrosourea or benzo(a)pyrene during the S phase following the administration of four different liver mitogens, namely, lead nitrate, ethylene dibromide, nafenopin, and cyproterone acetate, or during compensatory cell proliferation following partial hepatectomy or a necrogenic dose of CCl4. The carcinogen-altered hepatocytes were monitored as gamma-glutamyltransferase- or placental glutathione S-transferase-positive foci using a 2-wk promoting regimen consisting of 0.03% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results indicate that, unlike compensatory cell proliferation induced by partial hepatectomy or CCl4, the mitogen-induced cell proliferation did not result in a significant number of enzyme-altered islands, despite the fact that the extent of cell proliferation at the time of carcinogen administration, as monitored by the examination of labeled cells, is similar with both types of proliferative stimuli. PMID- 2889526 TI - Pleiotropic drug resistance in hepatocytes induced by carcinogens administered to rats. AB - The effect of hepatocarcinogen administration in vivo on the induction of pleiotropic drug resistance was studied in primary monolayer cultures of adult rat hepatocytes using a cytotoxicity assay in vitro. Dietary 2 acetylaminofluorene, 3'-methyl-4-dimethylaminoazobenzene, aflatoxin B1, ethionine, and diethylnitrosamine rapidly induced resistance to doses of Adriamycin, methotrexate, cycloheximide, and aflatoxin B1 which were cytocidal to normal hepatocytes from untreated rats. Up to 95% of some hepatocyte preparations became drug resistant before any new hepatocyte phenotypes could proliferate. Drug resistance was measured at 24 h after initiation of 2-acetylaminofluorene feeding and remained stable throughout the 16 wk of carcinogen exposure. When limited carcinogen exposure was followed by a return to a basal non-carcinogen containing diet for many months, the hepatocytes in the resultant hepatocellular carcinomas also displayed pleiotropic drug resistance, and the cells of the peritumorous liver did so to a lesser extent. Drug resistance was not induced by chronic administration of the tumor promoters phenobarbital, choline-deficient diet, phorbol, nor with 2,3,7,8-tetrachlorodibenzo-p-dioxin, but was induced to a variable extent by three hepatotoxins (ethanol, methotrexate, carbon tetrachloride). Whereas the early appearing drug resistance appears to be an adaptation of the liver to the presence of a toxic carcinogen, the late resistance which does not disappear after withdrawal of the inducing carcinogen may be a constitutive characteristic of chemically induced hepatocellular carcinomas. PMID- 2889527 TI - Distribution and biochemical characterization of somatostatin receptors in tumors of the human central nervous system. AB - Fifty-two brain tumors, consisting of 17 astrocytomas, 4 oligodendrogliomas, 20 glioblastomas, 3 neurinomas, 2 ependymomas, 1 neurofibroma, 1 ganglioneuroblastoma, 1 medulloblastoma, 1 plexus papilloma, 1 teratoma, and 1 germinoma, were tested for their content of specific somatostatin receptors using autoradiographic techniques or in vitro binding assays with membrane homogenates. Somatostatin receptors were found in most of the differentiated glia-derived tumors such as astrocytomas and oligodendrogliomas whereas the poorly differentiated glioblastomas were usually free of receptors. Tumors originating from neuroblasts, i.e., ganglioneuroblastoma and medulloblastoma, contained a high density of somatostatin receptors, whereas neurinomas and neurofibromas as well as the ependymomas, one teratoma, and one plexus papilloma were lacking such receptors. In one germinoma, low amounts of somatostatin receptors were observed over the lymphocytic elements. Receptor-positive tumors had saturable and high affinity receptors with pharmacological specificity for somatostatin and somatostatin analogues resembling that of normal human central nervous system tissue. In most instances, they could be labeled with two different iodinated radioligands, a somatostatin octapeptide derivative (204-090) or a somatostatin 28 analogue. This is the first time that somatostatin receptors have been shown to exist not only on neuronal structures of the central nervous system but also on glial elements. The precise function of such somatostatin receptors on glial cells, which may be different from neurotransmission, remains to be determined. PMID- 2889528 TI - Effect of a histamine H2-receptor antagonist, famotidine, on gastric secretion in healthy subjects. AB - The effects of 20 mg of famotidine or placebo on secretion of gastric juice and gastric acid were studied in ten healthy subjects in a randomized, crossover study. Gastric juice was aspirated and collected at hourly intervals for 24 hours after oral administration, and acid output was calculated based on gastric juice output and acid concentration. Secretion of gastric juice and acid output were lower after famotidine was administered than after placebo; over the 12-hour post administration period, the hourly acid concentrations were significantly lower after famotidine than after placebo. During the 12 hours after famotidine or placebo, gastric juice output was 180.7 +/- 32.1 ml (mean +/- SE) in the placebo group and 64.7 +/- 9.1 ml in the famotidine group (P less than 0.01); acid concentrations were 49.3 +/- 3.8 mmol/L in the placebo group and 9.6 +/- 3.1 mmol/L in the famotidine group (P less than 0.01); acid output was 8.89 +/- 1.59 mmol in the placebo group and 0.55 +/- 0.17 mmol in the famotidine group (P less than 0.01). These results support the effectiveness of a 12 hour or possibly a 24 hour dosing interval for famotidine. PMID- 2889529 TI - Effect of a new H2-blocker, famotidine, in reflux esophagitis among severely handicapped children. AB - Vomiting, hematemesis, and esophagitis resulting from gastroesophageal reflux or hiatal hernia are frequently observed in severely handicapped children. This study was conducted to determine whether the use of a new H2-antagonist, famotidine, could prevent recurrence of reflux esophagitis among such children. Seventeen severely handicapped, bedridden children admitted to a children's medical center between April 1985 and September 1986 were studied. All had vomiting or hematemesis as a main symptom, and the cause of esophagitis was suggested to be gastroesophageal reflux in 13 cases and hiatal hernia in four. Six had been previously treated with cimetidine or other drugs or a combination thereof without relief. Famotidine was administered at about 1 to 2 mg/kg/day, two times daily to patients weighing more than 10 kg and three times daily to those weighing less than 10 kg. In 13 cases, famotidine was administered intravenously for between seven and ten days and then given orally, while the rest were given the drug orally from the outset. The following results were obtained: (1) improvement was seen within seven days after start of famotidine treatment, and reduction of vomiting or hematemesis or both was reached within two weeks in 70% of cases and within three weeks in 94%; (2) famotidine was markedly effective in 29% and moderately effective in 41%; in no case was the drug ineffective; (3) no side effects were observed; five patients had transient, mild elevation of SGOT . SGPT, but this was not attributable to the drug. PMID- 2889530 TI - [Gamma-glutamyltransferase activity of amniotic fluid in the 2d trimester of pregnancy]. PMID- 2889531 TI - Genomic footprinting reveals cell type-specific DNA binding of ubiquitous factors. AB - Using in vivo dimethylsulfate footprinting, we have analyzed protein-DNA interactions within two regions upstream of the tyrosine aminotransferase (TAT) gene that are characterized by an altered chromatin structure in TAT-expressing as compared to nonexpressing cells. All the identified protein contacts to DNA are found exclusively in the TAT-expressing hepatoma cells. In vitro analyses of specific DNA-binding factors in crude nuclear extracts yield DNAase I footprints that correlate well with the binding sites in vivo. Surprisingly, all DNA-binding activities are present in nuclei of TAT-expressing and nonexpressing cells, indicating that the mere presence of factors is not sufficient for their interaction with a binding site in vivo. Genomic sequencing reveals methylation of CpG dinucleotides in the regions analyzed in nonexpressing cells, whereas no methylation is found in TAT-expressing cells. In vitro methylation at a cytosine residue within a footprint region prevents the interaction of a factor with its binding site. PMID- 2889533 TI - [Testicular dystopia in school-age children]. PMID- 2889532 TI - [Comparison of tofizopam with oxazepam in the treatment of anxiety neuroses]. PMID- 2889534 TI - 1,5-Benzoxathiepin derivatives. I. Synthesis and reaction of 1,5-benzoxathiepin derivatives. PMID- 2889535 TI - 1,5-Benzoxathiepin derivatives. II. Synthesis and serotonin S2-receptor-blocking activity of aminoalkyl-substituted 3,4-dihydro-2H-1,5-benzoxathiepin-3-ols and related compounds. PMID- 2889536 TI - The effects of fatigue on physician performance--an underestimated cause of physician impairment and increased patient risk. AB - Evidence is reviewed demonstrating the high level of drug and alcohol abuse and marital disharmony among physicians and the particularly high rate among anaesthetists. The relationship between these factors and the effects of fatigue is explored. The current evidence for reduction in physician performance and vigilance resulting from fatigue and sleep loss is reviewed. Supplementary indirect evidence is surveyed which suggests that increased experience may not compensate adequately for this reduced performance. Since hours of work can be controlled, it is essential that anaesthetists, their professional organizations and regulatory agencies ensure that pressure for efficiency does not result in fatigue and the consequent compromise of both patient and physician health and safety. PMID- 2889537 TI - Effect of vitamin E on the induction and evolution of enzyme-altered foci in the liver of rats treated with diethylnitrosamine. AB - The effects of dietary vitamin E (VE) on the steps of hepatocarcinogenesis, the induction and growth of gamma-glutamyltranspeptidase (GGT)-positive foci and their evolution into persistent nodules, were analyzed in the liver of rats treated with diethylnitrosamine (DEN). The induction of GGT-positive foci was inhibited by a diet containing 0.36-1.5% VE given after initiation with 200 mg/kg body weight (b.w.) DEN for 6 weeks with partial hepatectomy (PH) on week 3. The numbers and areas of GGT-positive foci were enhanced by diets containing 0.36 and 0.72% VE, given for 1 week after initiation with 10 mg/kg b.w. DEN and PH, followed by selection by 0.02% 2-acetylaminofluorene (AAF) and carbon tetrachloride (CCl4), but these were not enhanced by a diet containing 1.5% VE. Remodeling of hyperplastic nodules was not affected by the diet containing 0.72% VE given after initiation with DEN and selection for 12 weeks. The staining characteristics of GGT were different between remodeling and persistent nodules, except for those of the glutathione-S-transferase placental form (GST-P). The results obtained suggest that VE could prevent the very early events during hepatocarcinogenesis, the induction of phenotypically altered foci, but could no longer affect the later stages, the evolution of foci into persistent nodules. PMID- 2889538 TI - Effect of a rhodium complex on alterations of hepatic function in thioacetamide induced hyperplastic noduligenesis in rats. AB - An in vivo model of liver hyperplastic noduligenesis was induced in rats by long term administration of thioacetamide (TAM) (50 mg/kg/day i.p.). Three doses of 50 mg/kg of an antitumoral Rh(III) complex were administered at 14, 9 and 5 days before the end of TAM treatment. Plasma and urine were obtained from either TAM or Rh(III) complex or TAM plus Rh(III) complex treated rats to determine the interactions of both substances with the biochemical parameters related to liver function. The rise in alkaline phosphatase (ALP), leucine aminopeptidase (LAP), gamma-glutamyl transferase (GGT) and the unchanged activities in the aspartate and alanine aminotransferases (AST, ALT) in plasma of TAM-treated rats indicated that the disease induced by this substance can be considered as a chronic obstructive biliary disease with indices of cell proliferation and tumors. The increased concentration of bilirubin both in the plasma and urine of TAM-treated rats suggested liver cholestasis and hepatobiliary obstruction. The very low values of creatinine clearance indicated that there was some degree of kidney failure due to the effect of TAM. The increased concentration of ammonia both in plasma and urine were probably a consequence of the decreased flux in the urea cycle in the liver. The Rh(III) complex alone did not produce significant changes in the plasma enzyme activities. The only significant changes were found in the concentrations of uric acid and ammonia in the urine. When the Rh(III) complex was administered to TAM-treated rats, significant restoration of the following parameters were observed: plasma enzymatic activities, blood bilirubin and ammonia, uric acid and creatinine in the urine and the creatinine clearance. These results suggest that the altered liver function induced by TAM can be restored by Rh(III) complex. The mechanisms by which this complex acts to counteract the TAM-induced changes are not yet established. PMID- 2889540 TI - Beta-blockade--rational or irrational therapy for congestive heart failure? PMID- 2889539 TI - Immunologic identification of lymphocyte subsets in experimental murine myocarditis with encephalomyocarditis virus. Different kinetics of lymphocyte subsets between the heart and the peripheral blood, and significance of Thy 1.2+ (pan T) and Lyt 1+, 23+ (immature T) subsets in the development of myocarditis. AB - To clarify the immune mechanism in myocarditis, immunofluorescence techniques with laser flow cytometry were used to examine serial changes in lymphocyte subsets in the heart, spleen, and peripheral blood of DBA/2 and BALB/c mice inoculated with encephalomyocarditis virus (Experiment I). B cells were identified by staining with fluorescein isothiocyanate-labelled rabbit anti-mouse immunoglobulin. T-cell subsets were identified with rat anti-Thy 1.2, and nonpolymorphic Lyt 1 and Lyt 2 monoclonal antibodies plus fluorescein isothiocyanate-labelled anti-mouse immunoglobulin. On days 7 and 14 postinfection, the percentage of Thy 1.2+ (pan T) cells in both strains had decreased in the peripheral blood; B cells showed no significant changes throughout the entire period. On the other hand, Thy 1.2+ (pan T) and Lyt 1+, 23+ (precursor and immature) T cells appeared to occupy the major portion of the myocardium on days 7 and 14 when congestive heart failure developed. To confirm this, serial immunohistologic studies (immunoperoxidase staining) of the hearts of DBA/2 and BALB/c mice with encephalomyocarditis virus-induced myocarditis were performed (Experiment II). In Experiment II, most of the stained cells in the hearts of both strains were Thy 1.2 positive and Lyt 1 and Lyt 2 positive on days 7 and 14. Thus, Experiments I and II demonstrated that lymphocytes at the site of inflammation in acute viral myocarditis carried antigenic markers that differed from those of peripheral lymphocytes and suggested that Thy 1.2+ (pan T) cells, especially the Lyt 1+, 23+ subset (immature T cells and T-cell subset precursors) were involved in the development of myocarditis in these animals. PMID- 2889542 TI - Use of restriction fragment length polymorphism analysis for detecting carriers of "fragile X" syndrome. AB - Recombinant DNA technology promises to play an increasingly important role in the future of medicine. Application of this technology to the study of human disease will help us to define and clarify the molecular pathology of many clinical disorders, provide new diagnostic tools and approaches, and, finally, will provide new therapeutic agents including gene-replacement therapy. We have begun to exploit these powerful new techniques to aid in the laboratory diagnosis of several genetic disorders for which reliable assays are currently not available, such as "Fragile X" syndrome. PMID- 2889541 TI - The effect of amino acid L-glutamate on the extended preservation ex vivo of the heart for transplantation. AB - The present study was undertaken to assess the effect of L-glutamate on the extended preservation of the heart ex vivo added to a hypothermic preservative solution. Ten sheep hearts were removed after application of cold crystalloid potassium cardioplegia. The hearts were immersed in iced normal saline and right ventricular and left ventricular intraventricular balloons were connected to transducers to measure compliance. Thermistor probes were placed in the interventricular septum. The heart was mounted on a retrograde perfusion apparatus via the cannula in the brachiocephalic trunk and placed in an isolated glass cylinder. The perfusion apparatus consisted of a roller pump, a heat exchanger, and a pediatric membrane oxygenator. Control determinations and those after 8 hr of preservation were made while the hearts were perfused with enriched autologous blood. Right and left ventricular compliance, left ventricular systolic and diastolic pressures, right ventricular systolic and diastolic pressures, left ventricular dP/dt, coronary arteriovenous oxygen consumption, lactate production, and heart weight were measured. Results showed significantly improved left and right ventricular systolic function with L-glutamate preservation. Whole heart oxygen consumption in the L-glutamate group showed a 4% increase, while the placebo group showed a significant decrease in oxygen consumption after 8 hr of preservation. The glutamate-preserved hearts also showed no change in lactate production after 8 hr of preservation as compared with a 81% increase in the placebo group. After 8 hr of perfusion there was 67% increase in the heart weight of the control and a 42% increase in the L-glutamate group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889543 TI - Determination of delta-aminobutyric acid and other amino acids in cerebrospinal fluid of pediatric patients by reversed-phase liquid chromatography. AB - The reversed-phase liquid-chromatographic system described here is capable of resolving the neurotransmitter amino acids aspartic acid, glutamic acid, and gamma-aminobutyric acid (GABA) plus 21 other amino acids in cerebrospinal fluid (CSF) in a single analysis. The amino acids, derivatized with o-phthalaldehyde, are separated in 65 min. Concentrations of glutamine less than or equal to 600 mumol/L can be measured at the same time as GABA greater than or equal to 10 nmol/L. Using this method, we have determined reference intervals for amino acids, including GABA, in CSF in a group of pediatric patients who underwent lumbar puncture before myelography, and who were subsequently shown to have normal myelograms. These intervals are generally lower than those previously reported for childhood, but we believe this results from a more rigid selection of the control group. In addition, artifactual increases in concentrations of free neurotransmitters, caused by breakdown of amino acid conjugates, are minimized by (a) immediate freezing of the CSF samples to prevent enzyme-mediated changes, (b) omission of a deproteinization step, and (c) precolumn derivatization to reduce on-column breakdown of amide and peptide forms. PMID- 2889544 TI - Measurement of six enzymes with the Kodak DTSC Module, a physician's office analyzer. AB - We evaluated the performance of the Kodak DTSC Module for determination of alanine aminotransferase (ALT; EC 2.6.1.2), aspartate aminotransferase (2.5.1.2), alkaline phosphatase (3.1.3.1), creatine kinase (2.7.3.2), gamma glutamyltransferase (2.3.2.2), and lactate dehydrogenase (1.1.1.27). The DTSC is a "special chemistry" accessory for the DT60 analyzer; the same multilayer film technology as that of the Ektachem 700 is used. The overall precision, assessed over a three-month period with two serum-based quality control materials, ranged from 2.2 to 8.0%. DTSC results for patients' specimens correlated well with those by the Technicon RA-1000 analyzer. The performance of the analyzer in linearity and interference studies was satisfactory for clinical use. The DTSC is simple to operate and has no technique-dependent step; it should be useful for the physician's office laboratory. PMID- 2889545 TI - The crypt-villus distribution of the 10,000 Mr intestinal calcium binding protein in human jejunum. AB - The amount of small intestinal calcium-binding protein was studied in biopsies of human jejunum sectioned perpendicular to the long axis of the villi. Brush-border aminopeptidase N activity was measured to distinguish undifferentiated crypt cells from mature villus cells. The amount of calcium-binding protein as measured by enzyme-linked immunoadsorbent assay was highest at the villus tip and gradually decreased to near zero values in the crypt. The distribution of calcium binding protein observed is parallel to that found in vitamin D repleted rats. The present study indicates that the mature enterocyte in man is fully committed to express calcium-binding protein in accordance with the view that these cells are considered the most active in the calcium absorptive mechanism. PMID- 2889546 TI - Assay for cerebroside sulfate (sulfatide) sulfatase in cultured skin fibroblasts with the natural activator protein. AB - A simple procedure was developed to assay the ability of arylsulfatase A in extracts of cultured skin fibroblasts to degrade the natural substrate, sulfatide, in the presence of the physiological activator protein but without detergents. Inhibitory substances were removed by dialysis and by batch-wise ion exchange chromatography. The enzyme recoveries during purification were monitored with a newly developed method that employs the chromogenic substrate 4 nitrocatecholsulfate at an incubation temperature of 4 degrees C. The residual sulfatidase activities determined with this procedure in fibroblasts from patients with various forms of MLD correlated well with the severity of the disease. PMID- 2889547 TI - Clinical electroencephalographic variables suggesting extrapyramidal side effect risk. AB - Previous work has suggested that paroxysmal EEG dysrhythmias in psychiatric patients may be associated with an increased incidence of such diverse side effects as dyskinetic movements, extrapyramidal symptoms, iatrogenic seizures, and somatic/affective effects of oral contraceptives. The new analyses presented here extend these observations by using a large sample of 375 neuroleptically treated psychiatric patients with independently secured awake and asleep admission EEG studies. Those patients with minor paroxysmal EEG dysrhythmias are much more likely than normal EEG patients to receive anti-EPS medication during their treatment program. Furthermore, using data obtained from direct examination for EPS signs, neuroleptically treated patients with paroxysmal dysrhythmias as contrasted with those with normal EEGs, display statistically significant increases in EPS symptoms regardless of whether or not they are receiving concurrent anti-EPS medication at the time of examination. Prediction of side effect risk for the individual patient is not permitted by the strengths of associations reported for grouped data. However, it is suggested that future studies concerned with pharmacological side effect development in humans might benefit from stratification of samples by presence or absence of major and/or minor paroxysmal EEG patterns. PMID- 2889548 TI - Resolution of hypergastrinaemia after parathyroidectomy in multiple endocrine neoplasia syndrome type I (MEN type I). AB - The treatment of choice for gastric acid hypersecretion in MEN type I has now changed from total gastrectomy to the long-term administration of H2 receptor blockers or similar agents. However, the importance of parathyroidectomy for the concomitant hypercalcaemia is not fully realized. A case is reported of a subject with MEN type I, who was initially treated with parathyroidectomy and H2 receptor blockade. Following parathyroidectomy, there was a rapid fall of the markedly elevated gastrin levels to the upper limit of the normal range. During follow-up of 2.5 years, there has been no increase in serum gastrin, and the subject's gastric symptoms have resolved, despite the cessation of H2 blockade. Infusion of calcium to pre-operative levels and superimposed secretin stimulation after this period of time closely reproduced the pre-operative hypergastrinaemia. On screening, the subject's only child was found to have hypercalcaemia but normal serum gastrin levels and pituitary function; parathyroidectomy has been carried out. No abnormality of gastrin secretion has been found during follow-up. This case highlights the importance of early parathyroidectomy in this syndrome. PMID- 2889549 TI - Effects of SMS 201-995 in non-insulin-dependent diabetes. PMID- 2889550 TI - The effect of a new non-sedative H1-receptor antagonist (LN2974) on the itching and scratching of patients with atopic eczema. PMID- 2889551 TI - Interaction of vasopressin, angiotensin and alpha-adrenergic system in sodium depletion in the rat. AB - 1. The role of vasopressin in cardiovascular adaptation to sodium depletion was examined in rats after 6 days on a low sodium diet. Studies were performed after selective or combined blockade with d(CH2)5 Tyr(Me)AVP (AVPA), enalaprilat (CEI) and phentolamine (PHENTOL). AVPA alone had no effect on systemic haemodynamics or regional blood flow distribution. After CEI or PHENTOL pretreatment, AVPA led to significant falls in peripheral resistance and increases in cardiac output and renal blood flow. In sodium depletion, endogenous vasopressin acts as a vasoconstrictor hormone, particularly in the kidney, when either the renin angiotensin or alpha-adrenergic system is inhibited. PMID- 2889552 TI - The effects of beta-adrenergic blocking agents on blood lipid levels. AB - This review examines the effects of beta-adrenergic blocking agents on blood lipids. These agents have been effective in the treatment of angina and hypertension and in the reduction of recurrence of ischemic cardiac disease, such as myocardial infarction. Many beta blockers, however, have an adverse effect on blood lipids, especially by reducing high-density lipoprotein (HDL) cholesterol and increasing triglycerides. One result is an unfavorable influence on the cholesterol ratio (expressed either as low-density lipoprotein [LDL]/HDL or total cholesterol/HDL). These cholesterol parameters have been shown to have a strong influence on coronary heart disease (CHD) risk. Studies have shown that antihypertensive therapy has reduced the incidence of cerebrovascular disease but, in many instances, has not reduced the incidence of CHD. A hypothesis for this lesser effect on coronary disease is that antihypertensive agents may be adversely affecting blood lipids. Thus, while one major risk factor for CHD is reduced, another may be somewhat enhanced. Pharmacologic properties of some beta blockers such as peripheral alpha blockade (e.g., with labetalol) or intrinsic sympathomimetic activity (ISA) (e.g., with pindolol) may counteract some of these negative lipid effects. An investigational beta blocker, bevantolol, which will be marketed shortly in the United States, has been effective in antihypertensive therapy. Bevantolol has been shown to lower LDL cholesterol and not adversely affect HDL cholesterol; in this way, bevantolol favorably influences the serum lipoprotein profile. Whether this effect will have clinical significance remains to be seen. PMID- 2889553 TI - Neuromodulators and respiratory control in the infant. AB - In this review some of the neuromodulators involved in respiration control are discussed with special regard to the newborn. The term neuromodulator is defined relatively widely herein. Various types of neuromodulators have been found to affect respiratory control. These effect are more pronounced in the fetus and the neonate than in the adult. A disturbed balance between excitatory and inhibitory neuromodulators is postulated as causing the instability of respiratory control often seen in infants. PMID- 2889554 TI - The clinical pharmacology of bopindolol, a new long-acting beta-adrenoceptor antagonist, in hypertension. AB - Bopindolol is a new long-acting, nonselective beta-adrenoceptor antagonist with partial agonist activity. Its acute (24 hours, 2 mg, administered orally) and long-term (3 weeks, 2 to 4 mg) hemodynamic and hormonal effects were studied in a single-blind placebo-controlled trial in 10 hypertensive subjects. The initial response (mean +/- SE) to bopindolol was a fall in cardiac output (-12% +/- 2%) and heart rate (-11% +/- 2%). Mean arterial pressure began to fall 3 to 4 hours after administration in parallel with a decrease in systemic vascular resistance, which had increased initially. Twenty-four hours after administration, mean arterial pressure and systemic vascular resistance were reduced by 12% +/- 2% and 12% +/- 5%, respectively. By that time heart rate and cardiac output did not differ from baseline values despite beta-blockade. After 3 weeks of treatment mean arterial pressure had fallen by 9% +/- 2% and renal blood flow and glomerular filtration rate were not changed. One week after withdrawal from treatment mean arterial pressure and heart rate were no longer reduced, but beta blockade could still be demonstrated, establishing the long duration of action of the drug. PMID- 2889555 TI - Pharmacokinetics and pharmacodynamics of vecuronium administered by bolus and infusion during halothane or balanced anesthesia. AB - Vecuronium was administered to two patient groups as a single intravenous dose, 60 micrograms/kg, combined with an infusion, 1 microgram/min/kg. Anesthesia was maintained for the first group with a halothane-nitrous oxide technique; the second group received fentanyl-barbiturate-tranquilizer-nitrous oxide. As the infusion ended, plasma vecuronium concentrations were 0.34 (+/- 0.10) microgram/ml for the halothane group and 0.32 (+/- 0.07) microgram/ml for the fentanyl group, associated with 93% (+/- 8) and 88% (+/- 10) twitch depression, respectively. Vecuronium plasma concentration-time data were combined with the simultaneous intensities of neuromuscular blockade to model the kinetic-dynamic values for each patient. For the halothane group the steady-state volume was 0.21 (+/- 0.04) L/kg, the clearance was 2.9 (+/- 0.1) ml/min/kg, and the elimination half-life was 100 (+/- 36) minutes; for the fentanyl group these were 0.20 (+/- 0.08) L/kg, 3.2 (+/- 0.1) ml/min/kg, and 84 (+/- 43) minutes, respectively. Plasma concentrations associated with 50% blockade averaged 0.2 microgram/ml for both groups. Neither the pharmacokinetics nor the pharmacodynamics of vecuronium in humans differed between these two patient groups. PMID- 2889556 TI - Tissue cultivation as a method for preservation of human foetal islet parenchyma- a correlated biochemical, immunohistochemical and morphometric investigation. AB - Tissue culture of human foetal pancreas slices, obtained at a gestational age between 10 and 19 weeks, as a method of preservation and to pool the material before transplantation was investigated. Before and after 2 weeks of culture the pancreatic insulin content, the insulin secretion in response to glucose and isobutylmethylxanthin (IBMX) as well as the protein biosynthesis were measured. In addition, the distribution of the insulin immunoreactive cells was examined, as well as their relative volume density. After 2 weeks' culture an increase of the basal insulin secretion was observed; this was probably due to the glucose content (10 mmol/l) in the culture medium. Neither the stimulated insulin secretion, nor the protein biosynthesis, the insulin content, and the B-cell volume were altered by the used culture conditions. It was concluded that tissue culture is a suitable method to preserve human foetal pancreas slices before transplantation. PMID- 2889557 TI - The human interleukin-2 receptor: a molecular and biochemical analysis of structure and function. PMID- 2889558 TI - Current concepts in clinical therapeutics: anxiety disorders, Part 2. PMID- 2889559 TI - Alfentanil hydrochloride: a new short-acting narcotic analgesic for surgical procedures. AB - The chemistry, pharmacology, pharmacokinetics, clinical use, adverse effects, dosage, and administration of the short-acting synthetic narcotic analgesic alfentanil hydrochloride are reviewed. Alfentanil is a tertiary amine with an ionization constant of 6.5, resulting in approximately 10% ionization at physiologic pH. When compared with fentanyl, alfentanil has a faster onset and one third the duration of action, one fourth to one tenth the potency, less lipid solubility, greater protein binding, and a much greater unionized fraction at physiologic pH. Alfentanil is approximately 20-40 times less potent than sufentanil on a weight basis, but it has a faster onset and shorter duration of action. After i.v. injection, alfentanil is distributed in the body according to a two- or three-compartment model. When given to young and middle-aged patients for various surgical procedures, alfentanil has an elimination half-life of 70-99 minutes independent of the dose or route of administration. Clinical studies comparing alfentanil with fentanyl in short surgical procedures are reported; alfentanil produces earlier peak analgesic effect, faster recovery of consciousness, and a more pronounced narcotic effect without increased adverse effects. When alfentanil was given in high doses for anesthesia induction, chest wall rigidity occurred frequently. Like fentanyl, alfentanil was found to produce a high incidence of nausea and vomiting. It was more effective when administered by infusion than by bolus. Alfentanil is useful for supplementation of analgesia for outpatient surgical procedures, as an infusion for maintenance of anesthesia during surgery, and perhaps as an induction agent. PMID- 2889560 TI - Akathisia: a distressing complication of neuroleptic treatment. PMID- 2889561 TI - How closely do circulating blood glucose levels reflect feeding state in fowls? AB - 1. Amounts of food eaten in 30 min, by fasted-refed immature hens, were not correlated with plasma glucose levels before feeding, or with increases in glucose after feeding. 2. When previously fasted birds were given 0, 5, 10, 15 or 20 g food to eat, their plasma glucose increased by similar amounts with 10, 15 and 20 g, by slightly less with 5 g, and hardly at all with 0 g. 3. When food was removed from free-feeding birds, their plasma glucose levels declined slightly in 2 hr and then remained steady. They declined markedly further overnight, but recovered to a level higher than before deprivation when 10 g food was provided. 4. Four hours darkness during normal daytime had no effect on plasma glucose in fasted-refed birds, but sight of food and presentation of an empty food pan caused slight increases in glucose in 24-hr fasted birds. 5. It is concluded that blood glucose in fowls fluctuates around several "typical" levels, but that there is also much variation between and within birds. Direct (absorbed) and indirect (thermogenic) consequences of feeding probably both contribute to fluctuations in glucose, and these seem more likely to influence regulation of food intake in the longer-term rather than the short-term. PMID- 2889562 TI - Comparative thermoregulatory response to passive heat loading by exposure to radiofrequency radiation. AB - 1. Colonic and tail skin temperature of the unrestrained Fischer rat were measured immediately after a 90 min exposure to 600 MHz radiofrequency radiation in a waveguide-type system. Ambient temperature (Ta) was maintained at either 20, 28 or 35 degrees C. The specific absorption rate (SAR) in dimensions of W/kg was controlled at a constant level through a feedback control circuit. 2. The SAR needed to elevate colonic and tail skin temperature decreased with increasing Ta. For example, a 0.5 degrees C elevation in colonic temperature occurred at SARs of 4.3, 0.9 and 0.5 W/kg when Ta was maintained at 20, 28 and 35 degrees C, respectively. 3. Data from the present study were combined with data from earlier studies to assess the impact of varying Ta on the thermogenic effect of RF radiation in different species. In species ranging in mass from 0.02 to 3.2 kg, a double logarithmic plot of body mass versus SAR needed to elevate colonic temperature by 0.5 degrees C was linear and inverse with a high goodness of fit (r2 = -0.94). 4. The highly correlated allometric relationship shows that, as body mass decreases, the relative impact of Ta on the thermogenic effect of RF radiation increases. PMID- 2889563 TI - Interrelationship between metabolism of tritiated water, 22sodium and dry matter intake by beef cattle consuming wheat straw and poultry litter in free choice. AB - 1. Metabolism of tritiated water and 22sodium was studied in six beef cows under Mediterranean summer conditions in order to find whether the turnover of these tracers can be used to evaluate pasture intake. 2. The diet of the cows included ad libitum access to two components which were given separately in different troughs: one was poultry litter and the other was wheat straw, to simulate the dry pasture. 3. Voluntary daily dry matter intake (111 g/kg0.75) was unexpectedly high considering the low digestibility of the feed. 4. The assumptions of constant ratios of water intake to water turnover and of dry matter intake to water intake were confirmed. Consequently, dry matter intake was determined accurately from water turnover measurements. 5. Sodium intake was practically equal to sodium turnover and most of the sodium secreted in feces was of endogenous origin. 6. Pasture intake can be predicted from sodium turnover once the concentration in feed and water consumed is known. PMID- 2889564 TI - Influence of nitrate and nitrite on electrolyte transport by the rat small and large intestine. AB - 1. The influence of nitrate and nitrite on net absorption of electrolytes (Na+, K+, Cl-) and water from ligated loops was studied at various intestinal sites in rats. 2. Nitrate strikingly reduced Cl- absorption in rat proximal and distal colon, whereas Na+ absorption was reduced only moderately. Nitrite also reduced Cl- absorption in the colon. 3. Nitrate showed no significant effect on electrolyte absorption in the small intestine. 4. The results suggest that Cl /HCO3- on exchange is the major route of Cl- absorption in the colon, whereas this mechanism seems not to be of importance for Cl- absorption by the small intestine. PMID- 2889565 TI - Polyhormonal regulation of avian and mammalian corticosteroidogenesis in vitro. AB - 1. The combined actions of ACTH, corticosterone and prolactin (PRL) in the acute regulation of corticosteroidogenesis were investigated using isolated adrenocortical cells from intact and hypophysectomized (hypox) rats (Rattus norvegicus) and from intact male domestic fowl (Gallus gallus domesticus). 2. Exogenous corticosterone suppressed to about 50% ACTH-induced corticosterone production of cells from either species. This suppression, in part, was due to corticosterone degradation. 3. oPRL, in the presence or absence of ACTH, raised corticosterone production of hypox rat cells, but not intact rat and domestic fowl cells. 4. In addition, oPRL counteracted the corticosterone-induced suppression of net ACTH-stimulated corticosterone production of hypox rat and intact domestic fowl cells, but not intact rat cells. 5. The potency of oPRL with domestic fowl cells was 4 times that with hypox rat cells. 6. Furthermore, in domestic fowl cells, the effect of oPRL was Ca2+-dependent. PMID- 2889566 TI - Growth hormone and seawater adaptation in coho salmon, Oncorhynchus kisutch. AB - 1. Effects of growth hormone (GH) were examined on short-term aspects of seawater adaptation in coho salmon smolts. 2. Injection of somatostatin (SRIF) immediately prior to seawater entry suppressed plasma GH levels, but did not have any significant effects at 6 or 12 hr on hematocrits, plasma glucose or plasma Na+ levels. 3. Plasma GH levels increased 250% within 36 hr after seawater exposure. 4. Plasma glucose levels, in contrast, were significantly lower in the seawater fish after 36 hr post-exposure. 5. Plasma Na+ levels increased to 190 mEq/1 by 24 hr but subsequently returned to freshwater levels while hematocrits showed no significant changes over the 72 hr of exposure. 6. The significance of these results is discussed in terms of successful seawater adaptation in coho salmon. PMID- 2889567 TI - alpha-MSH (melanocyte stimulating hormone) and MCH (melanin concentrating hormone) actions in Bufo ictericus ictericus melanophores. AB - 1. The darkening actions of MCH (melanin concentrating hormone), alpha-MSH and the synthetic analog [Nle4, D-Phe7]-alpha-MSH on the toad, Bufo ictericus ictericus, melanophores were studied regarding the role of calcium in the hormone receptor coupling, signal transduction and intracellular pigment translocation. 2. In the absence of external calcium, MCH and both melanotropins still elicit maximal skin darkening. 3. Verapamil, a calcium-channel blocker, completely abolishes the alpha-MSH-induced response and partially inhibits MCH-induced darkening, although the calcium carrier, ionophore A23187, was unable to promote any pigment translocation. 4. Since darkening responses promoted by cyclic nucleotides proceeded normally in the presence of verapamil and extracellular calcium was not necessary for melanotropin dispersing action, it is suggested that the blocking activity obtained with verapamil is probably due to an impairment of the Ca2+-dependent adenylate cyclase activity. 5. Reversal of melanotropin-induced darkening could be obtained with melatonin, in both normal and Ca2+-free Ringer, whereas MCH darkening is reversed by melatonin only in the absence of calcium. 6. The results seem to indicate that calcium is not required for hormone receptor binding and pigment migration, whereas it is specifically needed for signal transduction. PMID- 2889568 TI - The influence of dehydroepiandrosterone on basal and gonadotrophin-stimulated testosterone secretion by Mongolian gerbil interstitial cells incubated or superfused in vitro. AB - 1. Testosterone secretion by Mongolian gerbil interstitial cells incubated in the absence of HCG linearly increased with cell concentration (1 x 10(5) cells: 0.6 ng/4 hr, 10 x 10(5) cells: 8.0 ng/4 hr). Addition of 100 mIU HCG resulted in a drastic increase of testosterone secretion which was linear between concentrations of 1 x 10(5) and 4 x 10(5) cells. 2. Compared to HCG-stimulated testosterone release, secretion was significantly higher by cells incubated with 60-100 ng DHEA. 3. During the 4-hr incubation period, 53-69% of added progesterone and 72-88% of added dehydroepiandrosterone (DHEA) were converted to testosterone by cells freshly prepared or stored for 1-3 days at 4 degrees C. On the other hand, prolonged storage at 4 degrees C resulted in a marked decrease of HCG-stimulated testosterone secretion. 4. Testosterone secretion by interstitial cells superfused in vitro increased with the length of HCG (100 mIU/ml) application from 0.08 to 0.22 ng/10(6) cells/min (10 and 60 min, respectively). A much faster and pronounced elevation was found when cells were stimulated with DHEA (200 ng/ml: 0.06-0.80 ng/10(6) cells/min, 0 and 20 min, respectively). 5. After interstitial cells have been stimulated with a DHEA (200 ng/ml) pulse for 30 min and then superfused with medium only for an additional 30 min, testosterone secretion remained significantly elevated and could not be further stimulated by superfusing medium which contained as much as 100 mIU/ml HCG. PMID- 2889569 TI - Isolation and characterization of single myocardial cells from the quail, Coturnix coturnix japonica. AB - 1. The enzymatic cell isolation technique was applied to the bird heart resulting in myocytes of which 10-50% maintained their spindle-shaped morphology, excluded the vital dye, Evans blue and tolerated physiological concentration of Ca2+ ions. 2. The length of spindle-shaped myocytes was on average 289 +/- 7 microns, and the maximum width was 10.2 +/- 0.3 microns. The mean length of the sarcomeres was 2.18 +/- 0.03 microns. 3. In electron micrographs the fine structure of the spindle-shaped myocytes looked normal--regular sarcomeric organization with clear A and I bands, mitochondria with tightly located cristae and well-developed sarcoplasmic reticulum (SR). 4. Most (80%) of the spindle-shaped myocytes were quiescent in physiological calcium concentration and practically all of them could be induced to twitch by electric field stimulation. Some beat spontaneously showing mostly slowly-propagating (135 +/- 6 microns/sec at 20 degrees C) contraction waves, so-called phasic contractions. Sometimes spontaneous twitch type contractions could also be seen. PMID- 2889570 TI - Physiological and behavioural responses in the hen (Gallus domesticus) to nociceptive stimulation. AB - 1. Physiological and behavioural parameters were examined in the hen in response to a noxious and non-noxious stimulus. 2. Two distinct patterns emerged depending on the type of stimulus (noxious----crouching, non-noxious----wingflapping). 3. The responses seen in the hen to the two different types of stimuli appear to be similar to those occurring in mammals. PMID- 2889571 TI - Glucose oxidation by adipose tissue of the edible dormouse (Glis glis) during hibernation and arousal: effect of insulin. AB - 1. The effect of insulin on U-14C-glucose oxidation by adipose tissue isolated from hibernating or arousing edible dormouse has been studied. 2. CO2 production derived from radioglucose was analysed point by point during in vitro rewarming (from 6 to 37 degrees C). 3. The rate of temperature increase was 2 degrees/5 min in order to mimic the rate of rewarming during the spontaneous arousal of the dormouse. 4. Insulin did not increase the glucose oxidation by the adipose tissue from hibernating dormouse whereas adipocytes from active animal present high insulin sensitivity. 5. These results suggest that insulin resistance occurs during hibernation. PMID- 2889572 TI - Sound reception in two anabantid fishes. AB - 1. Pure tone displacement sensitivity and bandwidth were measured from the saccule of the ear in two anabantid species (Trichogaster trichopterus and Helostoma temincki) using microphonic potentials with a 1 microV RMS threshold for the second harmonic of the stimulus frequency. 2. Saccular microphonics were recorded in both species from 80 to 1600 Hz, with lowest thresholds between 100 and 200 Hz. The overall microphonic response curves (sensitivity and bandwidth) of the two species were statistically similar to one another with an analysis of variance, although there were statistically different thresholds at 100 and 800 Hz. 3. The hair cell orientation patterns of the saccular epithelia differ in the two species. Consequently, the comparative sizes of the saccular sensory epithelium and numbers of sensory hair cells were examined. The saccular sensory epithelium of Helostoma is about 40% larger and contains nearly 50% more hair cells than the saccular epithelium of a comparably sized Trichogaster. 4. An extracranial air bubble, located in the suprabranchial chamber, is found in both species. The bubble has direct access to the saccular chamber in Trichogaster through a foramen which is absent in Helostoma. Despite the difference in morphology and the larger numbers of sensory hair cells in Helostoma, hearing sensitivity and bandwidth is similar in the two species. Although the structural differences in the auditory periphery do not affect pure tone sensitivity and bandwidth, other aspects of fish hearing such as frequency discrimination, discrimination of signals in the presence of noise, and/or sound localization ability may be affected by these structural differences. PMID- 2889573 TI - Metabolic utilization of diets by polyploid rainbow trout (Salmo gairdneri). AB - 1. Nitrogen (NH4) excretion and oxygen consumption were measured in four groups of juvenile rainbow trout (36-40 g): triploids obtained by a heat shock treatment (3n); triploids obtained by mating diploid females with tetraploid males (3n/4n); tetraploids (4n) and a diploid control (2n). 2. No differences in daily N excretion patterns and in N excretion rate measured as a percentage of N intake were detected between groups. 3. Oxygen consumption of the 2n group was significantly inferior to that of the 3n and 4n groups but not to the 3n/4n group. 4. SDA, specific dynamic action (measured as a percentage of the energy intake), ranged from 5.6 to 8.6% and was not different between groups. 5. Protein energy catabolism measured as per cent of total energy expenditure was significantly higher in the 2n group than in polyploid groups. PMID- 2889575 TI - Role of the pineal gland in the activity of nervous structures involved in sexual processes of the male rat. AB - 1. The role of the pineal gland and melatonin in the regulation of the sexual processes of the male rat has been studied by means of the O2-uptake of brain areas that are involved in these processes, i.e. the hypothalamus, amygdala, septal area and posterior cortex. 2. Inhibition of the O2-uptake of the above mentioned nervous structures was observed in the blinded and/or melatonin-treated rats or castrated + blinded rats. 3. The testes also showed a decreased O2-uptake when the rats were blinded and/or melatonin-treated. PMID- 2889574 TI - Gonadotropin stimulated androgen secretion of rainbow trout (Salmo gairdneri Richardson) testis in vitro. AB - 1. The secretion of five androgens was quantified from trout testes under GTH stimulation in vitro before and after the onset of milt production, and a general increase of basal and GTH stimulated androgen secretion was recorded during this period. 2. 11-Ketotestosterone, testosterone, and in spermiating males, 11 beta hydroxytestosterone as well showed GTH dependent concentration increases, while androstenetrione and 11 beta-hydroxyandrostendione were found in highly variable amounts. 3. 17 beta-Hydroxyandrogen glucuronides in the medium (with the exception of testosterone) and tissue androgens were by far exceeded by the free androgens in the medium. PMID- 2889576 TI - Effects of kainic acid on synaptic transmission in electroreceptors (the ampullae of Lorenzini) of skates. AB - 1. Effects of kainic acid (KA) on resting and evoked activities of the ampullary electroreceptor were studied in marine skates (Raja clavata). 2. Perfusion of the basal membrane with 10(-6)-10(-9) M KA produced significant and reversible changes in impulse activity depending on initial firing rate. 3. When synaptic transmission was blocked by perfusion with elevated Mg2+, the resting and evoked activities were restored if KA was added. 4. The results are consistent with the view that KA is a potent excitant of the ampullae receptors and its effects appear to be presynaptic. PMID- 2889577 TI - Temperature-mediated processes in teleost immunity: the effects of temperature on membrane immunoglobulin capping on channel catfish B lymphocytes. AB - 1. In order to better understand ligand-induced redistribution of membrane receptors and lymphocyte activation in ectothermic vertebrates, flow cytometry was used to monitor the effects of both in vivo acclimation temperature and in vitro assay temperatures on the kinetics of monoclonal antibody-induced membrane immunoglobulin (mIg) capping on channel catfish lymphocytes. 2. It was observed that the kinetics of mIg capping were dependent on in vitro assay temperatures, in vivo acclimation temperatures, and the length of time of in vivo acclimation. In the latter situation in vivo acclimation of fish to 27, 22 and 17 degrees C was considered complete after 3 weeks, while acclimation to 12 degrees C required a minimum of 5 weeks. 3. The energies of activation required for mIg capping ranged from 33 to 24 kcal/mol; lower energies of activation were observed with lower temperature acclimation. 4. It was also noted that the lower energies of activation were associated with concomitant decreases in cellular phospholipid saturated/unsaturated fatty acid ratios. 5. It appears that channel catfish B cell mIg capping, presumably a requisite for immune function, can be significantly affected by environmental temperatures; most likely such effects are attributable to changes in plasma membrane viscosities. PMID- 2889578 TI - Seasonal changes in circulating levels of thyroid hormones are not dependent on the age in Djungarian hamsters Phodopus sungorus. AB - 1. Plasma levels of total and free thyroxine (T4; FT4) and triiodothyronine (T3; FT3) were measured by radioimmunoassay in adult and senescent Djungarian hamsters at different times of the year. 2. Seasonal changes of both hormones were found in adult and senescent hamsters. 3. However, except for total thyroxine, the patterns were different in both groups of hamsters. 4. These results suggest, that in Djungarian hamsters age-related changes of thyroid function do not affect the secretory activity of the thyroid gland rather than the phase of the seasonal cycle. PMID- 2889579 TI - Determination of cardiac output and other reference physiology parameters in lightly anesthetized dogs. AB - 1. Cardiac output; arterial, pulmonary artery, central venous and pulmonary wedge pressures; heart rate, hematocrit, and plasma sodium and potassium; arterial and mixed venous blood gases; and respiratory rates were measured in 45 mixed sex, non-pregnant, clinically normal mongrel dogs of 8-30 kilograms body weight following light anesthesia with halothane/50% N20-02. 2. Arithmetic means and standard deviations were calculated to develop tables of reference values. 3. Mean measured cardiac outputs were found to be 31-59% higher in these dogs than the values indicated by published standards; cardiac indices were 30-44% higher; heart rates were 16-30% lower; calculated stroke volumes were 60-112% greater; and total peripheral resistances were 35-57% less than the standard published values. 4. All other measured or calculated parameters fell within previously published canine or human reference limits. PMID- 2889580 TI - Blood volume recovery in hemorrhaged Japanese quail. AB - 1. Blood volume and plasma biochemical changes and feed and water consumption in response to a hemorrhage by phlebotomy of 30% of the calculated total blood volume with and without replacement of blood volume with physiological saline were determined in juvenile male Coturnix coturnix japonica. 2. Plasma protein and osmolality decreased rapidly posthemorrhage and did not recover by 72 hr posthemorrhage. 3. Plasma glucose, Na+ and K+ increased within 1 hr postphlebotomy. Plasma Na+ returned to nonphlebotomized levels within 6 hr postphlebotomy. 4. Saline replacement of blood volume resulted in hypervolemia within 3-5 min postphlebotomy. 5. Phlebotomized quail receiving no saline recovered blood volume to 0 hr (nonphlebotomized) levels within 1 hr postphlebotomy. PMID- 2889581 TI - Hepatic lipogenesis in genetically lean and fat chickens. In vitro studies. AB - 1. Acetyl-coenzyme A carboxylase, malic enzyme, glucose 6-phosphate dehydrogenase and delta 9-desaturase activity was measured in liver extracts from 5- to 11-week old genetically lean or fat chickens. 2. A significant difference between the two lines of chickens was shown as concerns desaturating activity only, which was 45% higher in the fat animals than in the lean ones. 3. This result is consistent with the hypothesis of a higher rate of lipoprotein processing and secretion in the liver of the fat line chickens. PMID- 2889582 TI - Plasmid-mediated surface fibrillae of Yersinia pseudotuberculosis and Yersinia enterocolitica. Correlation with outer membrane protein YOP1, autoagglutination, and hemagglutination. PMID- 2889583 TI - Nonangiographic imaging of the pulmonary arteries: CT and MR. AB - Computed tomography (CT) has provided a imaging modality by which the central pulmonary arteries can be studied noninvasively. CT provides cross-sectional images which accurately depict the pulmonary arteries and adjacent structures. Magnetic resonance (MR) imaging with its ability to image vessels without contrast media provides a potential truly noninvasive means of examining the pulmonary arteries. These modalities are well suited to evaluate pathology involving the central pulmonary arteries. Normal CT and MR anatomy is illustrated and discussed. The clinical presentation and appearance of pathological processes involving the pulmonary arteries are described. PMID- 2889584 TI - [Prostaglandin E2 receptor and uterine bleeding caused by intrauterine devices]. PMID- 2889585 TI - An experimental contribution to the treatment of acute myocardial infarction. AB - 1. Benzodiazepines and strong analgesics raise considerably the ventricular fibrillation threshold and thus electrically stabilize the heart in the early stage of myocardial ischaemia. 2. Benzodiazepines markedly potentiate the electrostabilizing effect of the beta-blocker metipranolol. 3. Trimecaine per se does not electrically stabilize the heart in the first hour of ischaemia. When combined with a benzodiazepine, trimecaine stabilizes the heart also in this early stage of myocardial ischaemia. 4. Infusion of a benzodiazepine (midazolam) combined with fractionated administration of a potent analgesic (fentanyl) does not produce pronounced changes in the haemodynamics and ventilation of healthy subjects. 5. Benzodiazepines and strong analgesics exert a favourable effect on the neurovegetative stress response in the early stage of acute myocardial ischaemia. They can be therefore recommended as a component in the treatment of patients with acute myocardial infarction. PMID- 2889586 TI - Hepatic bile formation in the rat. Addition of vasoactive intestinal peptide to the equation. AB - While changes in gastric, pancreatic, and intestinal secretion in response to more recently identified gastrointestinal peptides have been characterized, there has been less investigation into effects of these hormones on hepatic bile production. The isolated perfused rat liver model has been used to examine effects of vasoactive intestinal peptide (VIP), somatostatin, bombesin, and thyrotropin-releasing hormone (TRH) on bile flow and bile acid transport. No changes were seen following bolus administration of bombesin (3 X 10(-8)-1.5 X 10(-6) M) or TRH (3 X 10(-7)-3 X 10(-6) M), while somatostatin (6 X 10(-6) M) produced a small decrease in bile flow without any change in bile acid output. VIP (3 X 10(-7) M) caused a highly significant increase in both volume of bile flow (0.85 +/- 0.8 to 1.11 +/- 0.09 microliter/min/g liver, P less than 0.001) and bile acid output (31.6 +/- 1.5 to 43.2 +/- 1.7 nmol/min/g liver, P less than 0.001). Elimination of Ca2+ from liver perfusate did not prevent VIP-induced increases in bile flow and bile acid output, and no synergistic effect of concomitant theophylline administration was observed. While effects of VIP on bile flow appear to be due to alterations in hepatic transport of bile acids, the exact mechanism(s) producing these changes remains to be elucidated. PMID- 2889588 TI - GGT test. PMID- 2889587 TI - Malignant insulinoma with metastasis to gallbladder and bone, accompanied by past history of peptic ulcer and hyperthyroidism. AB - A case of a malignant insulinoma in a 53-year-old female is presented. In 1973, the patient underwent caudal pancreatectomy for a malignant insulinoma. Ten years later, it was discovered that the insulinoma had spread to the bones. On admission for cholecystectomy because of a gallbladder polyp and gallstones, she often experienced hypoglycemic attacks, and both calcium and glucagon provocation tests elicited marked release of insulin. Selective angiography of the common hepatic artery showed a tumor blush near the hilum of the liver. Immunohistochemical staining of the gallbladder polyp and the bone tumors proved positive for insulin. Plasma levels of insulin and prolactin were abnormally high. The patient had also been treated for a perforated duodenal ulcer and hyperthyroidism. It is concluded that this may have been a case of a multiple endocrine neoplasia. PMID- 2889589 TI - [Legal problems of the use of opioids in the rescue service]. PMID- 2889590 TI - The effect of the nucleocytoplasmic ratio on protein synthesis and expression of a stage-specific antigen in early cleaving mouse embryos. AB - The nucleocytoplasmic ratio of fertilized mouse eggs was manipulated by removing or injecting cytoplasm by micropipette, and bisection of denuded eggs to obtain both pronuclei in one half of the eggs cytoplasm. The experimental eggs were capable of cleavage to the morula stage and, in some instances, developed to the blastocyst stage similar to unmanipulated eggs. The removal of large quantities of cytoplasm by micropipette and injecting them into a recipient egg did not provide sufficient numbers of viable eggs, whereas transfer of smaller quantities (about a quarter of the cytoplasm) was less deleterious, at least for recipient eggs. However, the alteration of the nucleocytoplasmic ratio by this method was not of the correct magnitude for the purpose of this experiment. Therefore, bisection was the preferred method whereby the nucleocytoplasmic ratio was doubled. This resulted in both pronuclei residing in one half of the egg's cytoplasm. Half eggs with one pronucleus (haploid) but retaining a nucleocytoplasmic ratio similar to unmanipulated control eggs served as additional controls for the bisection experiments. Protein synthesis was analysed by two-dimensional gel electrophoresis, showing that the 2-cell- and 4-cell-stage bisected embryos with double and normal nucleocytoplasmic ratio expressed equivalent protein synthesis patterns as control embryos of the same stage. Likewise, the stage-specific surface antigen SSEA-1 did not appear before the 6- to 8-cell stage. Also in cytoplasm transfer experiments, there was no indication that altering the nucleocytoplasmic ratio in either direction changed the timing of stage-specific gene expression. These results support the idea that stage specific gene activity during early mouse cleavage might proceed in parallel to DNA replication cycles and is independent of the nucleocytoplasmic ratio. PMID- 2889591 TI - Developmental and spatial patterns of expression of the mouse homeobox gene, Hox 2.1. AB - The Hox 2.1 gene forms part of a cluster of homeobox-containing genes on mouse chromosome 11. Analysis of Hox 2.1 cDNAs isolated from an 8 1/2-day p.c. mouse embryo library predicts that the gene encodes a 269 amino acid protein (Mr, 29,432). This deduced protein contains a homeobox 15 amino acids from the carboxy terminus and is very rich in serine and proline. A second partially conserved region present in several other genes containing homeoboxes, the hexapeptide Ile Phe-Pro-Trp-Met-Arg, is located 12 amino acids upstream of the homeodomain and is encoded by a separate exon. Analysis of Hox 2.1 gene expression reveals a complex and tissue-specific series of RNA transcripts in a broad range of fetal tissues (lung, spinal cord, kidney, gut, spleen, liver and visceral yolk sac). Comparison of the temporal patterns of gene expression during development and in the adult suggests that Hox 2.1 is regulated independently in different tissues. Evidence is also presented that transcripts from other loci have extensive homology to the Hox 2.1 gene in sequences outside of the homeobox. In situ hybridization shows that Hox 2.1 transcripts are regionally localized in the spinal cord in an apparent anterior-posterior gradient extending from the hind brain. The distribution of RNA also displays a cell-type specificity in the lung, where mesodermal cells surrounding the branching epithelial cell layer accumulate high levels of Hox 2.1 transcripts. PMID- 2889592 TI - [Physical exhaustion and fatal heat stroke]. PMID- 2889593 TI - [Takayasu's arteritis in a young girl with hypertension]. PMID- 2889594 TI - Isolation and characterization of tetrahydropterin oxidation products generated in the tyrosine 3-monooxygenase (tyrosine hydroxylase) reaction. AB - The catalytic mechanism of tyrosine 3-monooxygenase (tyrosine hydroxylase, EC 1.14.16.2), isolated from the cytosolic fraction of bovine adrenal medulla, was studied by new techniques of product isolation and characterization. Using either (6R)-tetrahydrobiopterin, (6RS)-tetrahydroneopterin, or 6-methyl tetrahydropterin, as the cofactors, three enzymatic oxidation products could be isolated and identified from the reaction mixture by high-performance liquid chromatography and rapid-scanning spectroscopy: (a) the 4a-hydroxy derivatives, (b) the quinonoid dihydropterins, and (c) the stable 7,8-dihydropterins. Stopped flow spectroscopy revealed that the formation of the 4a-hydroxy-tetrahydropterins preceded the formation of the quinonoid forms with both L-tyrosine and L phenylalanine as the substrate. The formations of 4a-hydroxy-tetrahydropterins and hydroxylated amino acids were tightly coupled as recently shown in the phenylalanine 4-monooxygenase reaction [Haavik, J., Doskeland, A. P. & Flatmark, T. (1986) Eur. J. Biochem. 160, 1-8]. No detectable carbinolamine dehydratase activity was present in the enzyme preparation. PMID- 2889595 TI - Association of the precursor of cathepsin D with coated membranes. Kinetics and carbohydrate processing. AB - Specific anti-chlathrin antibodies were used to isolate clathrin-coated membranes from homogenates of metabolically labelled fibroblasts. The isolated membranes were extracted with detergents and cathepsin D was isolated from the extracts. The 53-kDa precursor of cathepsin D was transiently associated with the coated membranes with a maximum approximately 60 min after synthesis. At maximum about 4.0% of the precursor was recovered with the coated membranes and the associated precursor contained complex oligosaccharides. The proportion of complex oligosaccharides in the coated membrane-associated precursor did not differ from that in the total precursor. These data support the view that coated membranes are involved in the transport of cathepsin D between trans Golgi and a prelysosomal organelle. PMID- 2889596 TI - Characterization of the Na+-stimulated ATPase of Propionigenium modestum as an enzyme of the F1F0 type. AB - The ATP-hydrolyzing activity of Propionigenium modestum was extracted from the membranes with Triton X-100 or by incubation with EDTA at low ionic strength. The ATPase in the Triton extract was highly sensitive to dicyclohexylcarbodiimide but not to vanadate. These properties are characteristic for enzymes of the F1 F0 type. The ATPase was specifically activated by Na+ ions yielding a 15-fold increase in catalytic activity at 5 mM Na+ concentration. The additional presence of 1% Triton X-100 caused a further 1.5-fold activation. In the absence of Na+ Triton stimulated the ATPase about 13-fold. The Triton-stimulated ATPase was further activated about 1.5-2-fold by Na+ addition. The ATPase extracted by the low-ionic-strength treatment was purified to homogeneity by fractionation with poly(ethylene glycol) and gel chromatography. The enzyme had the characteristic F1-ATPase subunit structure with Mr values of 58,000 (alpha), 56,000 (beta), 37,600 (gamma), 22,700 (delta), and 14,000 (epsilon). The F1-ATPase was not stimulated by Na+ ions. The membrane-bound ATPase was reconstituted from the purified F1 part and F1-depleted membranes, thus further indicating an F1 F0 structure for the ATPase of P. modestum. Upon reconstitution the ATPase recovered its stimulation by Na+ ions, suggesting that the binding site for Na+ is localized on the membrane-bound F0 part of the enzyme complex. PMID- 2889597 TI - Structural characterization of peptides derived from prosomatostatins I and II isolated from the pancreatic islets of two species of teleostean fish: the daddy sculpin and the flounder. AB - The primary structures of three peptides from extracts from the pancreatic islets of the daddy sculpin (Cottus scorpius) and three analogous peptides from the islets of the flounder (Platichthys flesus), two species of teleostean fish, have been determined by automated Edman degradation. The structures of the flounder peptides were confirmed by fast-atom bombardment mass spectrometry. The peptides show strong homology to residues (49-60), (63-96) and (98-125) of the predicted sequence of preprosomatostatin II from the anglerfish (Lophius americanus). The amino acid sequences of the peptides suggest that, in the sculpin, prosomatostatin II is cleaved at a dibasic amino acid residue processing site (corresponding to Lys61-Arg62 in anglerfish preprosomatostatin II). The resulting fragments are further cleaved at monobasic residue processing sites (corresponding to Arg48 and Arg97 in anglerfish preprosomatostatin II). In the flounder the same dibasic residue processing site is utilised but cleavage at different monobasic sites takes place (corresponding to Arg50 and Arg97 in anglerfish preprosomatostatin II). A peptide identical to mammalian somatostatin 14 was also isolated from the islets of both species and is presumed to represent a cleavage product of prosomatostatin I. PMID- 2889598 TI - Quantitative measurement of the error in the cryptic stereospecificity of methylmalonyl-CoA mutase. AB - 1. Samples of methylmalonyl-CoA and (2H3)methylmalonyl-CoA were prepared by a combination of chemical and enzymic methods. After ion-exchange chromatography the unlabelled methylmalonyl-CoA was pure, the deuterated substance contained 11 12% dephospho-CoA derivative. 2. The sample of unlabelled methylmalonyl-CoA was incubated in deuterated buffer with catalytic amounts of methylmalonyl-CoA mutase, epimerase, and coenzyme B12. The progress of the reaction was monitored directly by 1H-NMR spectroscopy at 500 MHz. After equilibrium was established, a slow mutase-catalysed deuterium incorporation into migratable positions of succinyl-CoA was observed. 3. The sample of (2H3)methylmalonyl-CoA was incubated in unlabelled buffer with a mixture of methylmalonyl-CoA mutase, epimerase and coenzyme B12. In withdrawn aliquots, the reaction was interrupted by acidification and the lyophilised samples were examined by 1H-NMR spectroscopy in deuterium oxide. Both rearrangement and protium incorporation into migratable positions of succinyl-CoA were monitored. 4. At comparable methylmalonyl-CoA to succinyl-CoA conversion rates, deuterium loss from migratable positions was 4-6 times faster than the corresponding protium loss. It is confirmed that the stereochemical error of the mutase is amplified by isotope discrimination when deuterium is in migratable positions, whereas it is diminished when protium is in migratable positions. PMID- 2889599 TI - The effects of beta-adrenergic blocking agents on atherosclerosis and its complications. AB - Epidemiologic and experimental data are reviewed to determine whether treatment with beta-adrenergic blocking agents ('beta blockers') is likely to be antiatherogenic. Both indirect and direct evidence are considered. Indirect evidence is derived from studies of the effects of beta blockers on the risk factors for atherosclerosis, or on the disease sequelae of atherosclerosis. Direct evidence refers to studies in which atherosclerosis is an endpoint. Regarding indirect evidence, the data generally are consistent with a retarding or neutral effect of beta blockers on atherosclerosis. For example stroke incidence is reduced when hypertension is treated with beta blockers. About half of these same studies also show a reduction in the incidence of myocardial infarction, a complication that may be more closely related to atherosclerosis extent and severity than is stroke, which can have a nonatherosclerosis origin. The most important potential negative effect of beta blockers occurs with respect to serum lipid concentrations. However, there is no evidence that atherosclerosis is worsened as a result of pharmacologically induced alterations of serum lipids. The direct evidence more clearly indicates a retarding effect of beta blockers on atherosclerosis, with 11 of 13 studies having outcomes in this direction. However, interpretation of these studies is complicated by the fact that all of the data are derived from animal models, some of which are not similar to human beings in the development of atherosclerosis. Also, the studies are diverse, not only in the research designs and species utilized, but also in the type of beta blocker employed, the degree of beta blockade achieved, and the anatomic location of lesions. In summary, the data suggest that treatment with beta blockers may retard atherosclerosis. A more definitive answer requires efforts in two directions: (a) studies on atherosclerosis in selected populations of human beings, using cineangiography or autopsy material; and (b) additional, well controlled studies in appropriate animal models. PMID- 2889600 TI - By what means might beta blockers prolong life after acute myocardial infarction? PMID- 2889601 TI - Potential role of somatostatin analogues in the treatment of cancer. PMID- 2889602 TI - Enhanced biliary gamma-glutamyltransferase excretion following prolonged alcohol consumption in rats. AB - In order to study the question of whether chronic ethanol consumption may alter the biliary excretion of gamma-glutamyltransferase (gamma-GT), female rats were pair-fed nutritionally adequate liquid diets containing either ethanol (36% of total calories) or isocaloric carbohydrates for 24 days. Compared to pair-fed controls, the administration of the alcohol-containing diet resulted in an increased biliary excretion of gamma-GT (5.84 +/- 0.73 mU 6 h-1 100 g-1 b.w. vs. 8.82 +/- 0.79, P less than 0.001). This was associated with a corresponding enhanced biliary output of total bile acids. An apparent linear relation between the biliary output rates of gamma-GT and those of total bile acids was observed both in alcohol-fed animals (r = 0.83) and in their pair-fed controls (r = 0.95). In addition, there was a significant increase of gamma-glutamyltransferase activities in the liver homogenate and in liver plasma membranes, both in fractions rich in bile canalicular and basolateral membranes and in those rich in blood sinusoidal site. Serum gamma-glutamyltransferase activities as well as serum bile acid concentrations were also enhanced by 96.8% (P less than 0.001) and 233% (P less than 0.001), respectively. These data show that chronic alcohol consumption enhances hepatic gamma-GT activities, leading to an increased efflux of gamma-GT into the bile and possibly into the blood out of the liver cell. Furthermore, these data suggest the involvement of bile acids with their solubilizing properties for the biliary excretion of gamma-GT. PMID- 2889603 TI - Relationship between growth hormone and somatomedin-C levels in untreated acromegaly, after surgery and radiotherapy and during medical therapy with sandostatin (SMS 201-995). AB - Several conflicting reports have been published with regard to the relationships between circulating growth hormone (GH), Somatomedin-C (SM-C) levels and clinical activity during different stages of therapy of acromegaly. We did not find a significant correlation between (fasting, post-prandial and mean 24-h) plasma GH and SM-C concentrations in twenty-two untreated acromegalic patients. There was a statistical significant correlation, however, if only the GH levels below 100 micrograms 1(-1) were considered (n = 18 patients, P less than 0.01). The distribution of molecular forms of GH ('little', 'big' and 'big-big') did not differ between the four patients with GH levels above 100 micrograms 1(-1) and in four patients with levels between 40 micrograms 1(-1) and 80 micrograms 1(-1). Therefore, it is suggested that GH levels of 80-100 micrograms 1(-1) maximally activate Somatomedin-C production in man and that further increases in GH in general will not result in a further increase in SM-C generation. There was a significant correlation between GH and SM-C levels in forty-nine acromegalic patients after surgery and/or radiotherapy (P less than 0.001). In twenty-three of thirty-one patients with elevated SM-C levels the disease was subjectively still active, while this was the case in none of the patients with normal SM-C levels. In eight patients the disease was considered not to be clinically active any more, despite slightly increased SM-C levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889604 TI - Equal potency of nifedipine to inhibit alpha 1-(dobutamine and BDF 6143) and alpha 2-adrenoceptor (B-HT 920) induced pressor responses in pithed rats; lack of effect of phenoxybenzamine. AB - Intravenous (i.v.) dobutamine and BDF 6143 were partial agonists in increasing diastolic pressure in beta-adrenoceptor-blocked pithed rats. The log dose-pressor effect curves were not influenced by yohimbine (1 mg/kg i.v., -15 min) but were markedly shifted to the right by prazosin (0.1 mg/kg i.v., -15 min) indicating the exclusive involvement of alpha 1-adrenoceptors. Nifedipine (0.1-1 mg/kg i.a., -15 min) non-competitively inhibited the pressor effects of dobutamine and BDF 6143 as well as of the alpha 2-adrenoceptor agent B-HT 920 with equal potency. The -log ED50 values calculated for nifedipine amounted to 6.25 +/- 0.12, 6.16 +/ 0.14 and 6.20 +/- 0.10, respectively. Phenoxybenzamine (3 or 10 micrograms/kg i.v., -60 min) did not affect the effectiveness of nifedipine (0.1 mg/kg) to inhibit the pressor effects of dobutamine and BDF 6143. Following treatment with Bay k 8644 (1 mg/kg i.a., -15 min), the log dose-pressor effect curves for dobutamine and BDF 6143 were shifted to the left and the maximum responses were elevated. Our findings suggest that the alpha 1-adrenoceptor-induced pressor effects of dobutamine and BDF 6143 rely heavily on the influx of Ca2+, and are indistinguishable in this respect from the effects initiated by alpha 2 adrenoceptor stimulation. The data further support the view that the sensitivity of alpha-adrenoceptor-mediated pressor effects to inhibition by Ca2+ entry blockers depends on the extent to which Ca2+ influx contributes to the overall response and is not determined by the intrinsic activity or by the receptor reserve of the alpha-adrenoceptor agonist. PMID- 2889605 TI - Desipramine given repeatedly enhances behavioural effects of dopamine and d amphetamine injected into the nucleus accumbens. AB - The effect of desipramine (DMI) was studied after its repeated administration (10 mg/kg p.o., twice daily, 14 days) to rats, on the action of dopamine and d amphetamine injected bilaterally into the nucleus accumbens. DMI, applied repeatedly but not acutely, prevented the sedative effect of dopamine and enhanced its stimulating action, as assessed by the open-field test. Repeated administration of DMI also enhanced d-amphetamine-induced locomotor hyperactivity. The number of [3H]SCH 23390 binding sites (D-1) in the limbic system decreased while the number of [3H] spiperone ones (D-2) remained unchanged. The results indicate that, like other antidepressant drugs studied earlier, DMI enhances neurotransmission in the dopamine mesolimbic system (nucleus accumbens) of the rat. PMID- 2889606 TI - Hypothermia and poikilothermia induced by a kappa-agonist opioid and a neuroleptic. AB - When an opioid acting selectively at the kappa opioid receptor is administered subcutaneously to rats along with a neuroleptic at an ambient temperature of 20 degrees C a marked hypothermia ensues. The combination of U-50,488H (a kappa agonist) and chlorpromazine (a neuroleptic) caused a drop in body temperature amounting to as much as 11 degrees C, with all animals recovering after 24-48 h. Naloxone partially reversed the hypothermia. Similar, but less dramatic, decreases in body temperature occurred with other neuroleptics and weaker kappa agonists. The induction of poikilothermia was indicated when the body temperature approached the environment temperature and lethality resulted in 100% of the animals at ambient temperatures of 5 degrees C or 35 degrees C. The potential utility of this or similar combinations of drugs lies in such diverse applications as cardiac surgery, treatment of the near-drowning syndrome and space travel. PMID- 2889607 TI - Synergistic activity of sodium cromoglycate and beta 2-stimulants in rat lung anaphylaxis. AB - Using a model of passive anaphylactic bronchoconstriction in the rat, the combined inhibitory effects of sodium cromoglycate and the beta 2-adrenoceptor agonists fenoterol and salbutamol were shown to be synergistic. Synergism was most evident in animals strongly sensitised with relatively high levels of IgE antibodies, in which the individual drugs showed reduced potency. PMID- 2889609 TI - Weakening of naloxone antagonism in vitro and in vivo with octreotide (SMS 201 995). AB - Octreotide, a potent long-acting somatostatin analogue, has been shown to have a wide range of physiological actions. We have demonstrated a somatostatin-like inhibition of the electrically evoked contractions of the mouse vas deferens and an opioid antagonistic property in the same tissue. In addition, pretreatment with octreotide reduced the potency of naloxone antagonism in vitro in the mouse vas deferens and in vivo in the mouse charcoal meal test. The latter effect suggests that the agonist receptor interactions are taking place on sites allosteric to the agonist site and that the conventionally accepted concept of opioid antagonism may have to be modified. PMID- 2889608 TI - Changes in the biological activity of autacoids during passage through the human perfused fetoplacental lobule. AB - Changes in the biological activities of a number of autacoids after a single passage through the human perfused fetoplacental lobule have been assessed by bioassay, whilst recording fetal vascular resistance. Bradykinin did not affect vascular resistance, but its biological activity on the superfused bioassay tissues fell by approximately 98%, whereas des-Asp1-angiotensin I activity increased at least 80-fold and the vascular resistance rose. All these effects were inhibited by captopril. Angiotensin II increased vascular resistance but its activity on the bioassay tissues was not changed. 5-Hydroxytryptamine activity was reduced by 67-90% and resistance to flow was not affected. The activities of prostaglandins D2, E2, and F2 alpha were slightly reduced. Prostaglandins D2 and F2 alpha caused vasoconstriction, their maximum effects being greater than those of either of the angiotensins. The TxA2-mimetic U46619 was approximately 90 times more potent than PGF2 alpha, as a vasoconstrictor, but the maximal effects were comparable. Thus, autacoid activity can be reduced, augmented or not affected during passage through the human perfused fetal placental vasculature. PMID- 2889610 TI - Primary afferent terminal excitability in the normal and spastic mutant mouse spinal cord. AB - A microcomputer-based system has been used to apply the technique of excitability testing to the study of the actions of a range of pharmacological agents on the excitability of single primary afferent terminals in the mouse spinal cord in vitro. GABAA analogues all evoked increases in excitability that were bicuculline sensitive. GABA itself also evoked biphasic changes in excitability, or occasionally only suppressed terminal excitability. This latter effect was often enhanced in the presence of bicuculline, and resembled the action of the GABAB agonist, baclofen. The GABAA action could be enhanced by concurrent application of either benzodiazepine, midazolam or flurazepam. Bicuculline alone frequently decreased excitability. This action could be abolished by blocking synaptic activity with a low Ca2+ high Mg2+ superfusate, and was therefore considered to be due to reduction of the tonic action of GABA released at synaptic connections. Comparison of the action of these agents on terminals in the spastic mutant mouse showed an increased sensitivity of the GABA response to the benzodiazepines in mutant animals. PMID- 2889611 TI - Isapirone is a partial agonist at 5-hydroxytryptamine 1A (5-HT1A) receptors in the rat hippocampus: electrophysiological evidence. AB - Using iontophoretic techniques we observed that in vivo isapirone (TVX Q 7821), a selective ligand for the 5-HT1A binding site, at low ejection currents (5-30 nA) antagonised 5-HT and 8-hydroxy-2-(di-n-propylamino) tetralin (DPAT)-induced suppression of hippocampal unit activity, with little effect on baseline firing rate itself. At higher ejection currents (20-100 nA) or following prolonged application, isapirone inhibited unit firing. Responses to GABA were unaffected by isapirone. These data demonstrate that isapirone is a 5-HT1A receptor antagonist with partial agonist properties on 5-HT sensitive neurones in the rat hippocampus. PMID- 2889612 TI - Histochemical studies on gamma-glutamyltranspeptidase activity of pancreatic acinar cell lesions induced by 4-hydroxyaminoquinoline 1-oxide and/or azaserine in rats. AB - The utility of gamma-glutamyltranspeptidase (gamma-GTP) as an enzyme marker during pancreatic acinar cell carcinogenesis in rats was assessed by measuring its enzyme-histochemical performance in pancreatic acinar cell lesions induced by 4-hydroxyaminoquinoline 1-oxide (4-HAQO) and/or azaserine in partially pancreatectomized Fischer 344 and Wistar rats. Rats were given a single intravenous injection of 4-HAQO (10 or 7 mg/kg body weight) 3 days after partial pancreatectomy followed by intraperitoneal injections of azaserine (30 mg/kg) once a week for 10 weeks, or the same treatment without azaserine. The animals were sacrificed at 3, 6, 10, 12 and 18 months. 4-HAQO predominantly induced basophilic foci in Fischer rats, while in Wistar rats acidophilic foci and acidophilic hyperplastic nodules were predominant. A preferential enhancement of the induction of acidophilic foci and hyperplastic nodules was exhibited in Fischer rats following co-administration with azaserine. Normal acinar cells were positive for gamma-GTP. 90 to 100% of basophilic foci were either negative or slightly positive for gamma-GTP, whilst 68 to 98% of acidophilic foci were positive. The gamma-GTP activities of acidophilic hyperplastic nodules were more variable between nodules than within nodules, and either co-administration of azaserine or extension of experimental duration time appeared to increase the gamma-GTP positive nodules. Between the gamma-GTP positive and decreased nodules, no histological but some morphometrical differences were observed. As far as the nodules induced by 4-HAQO in Fischer rats were concerned, all of the gamma-GTP decreased nodules had thin fibrous capsules and exhibited ultrastructurally more atypia than the positive ones. Present study thus revealed that gamma-GTP is neither a useful nor invariable enzyme marker during pancreatic acinar cell carcinogenesis in rats. PMID- 2889613 TI - Sympatho-inhibitory mechanisms acting at sympathetic ganglia to attenuate hypothalamic-induced pressor effect in the cat. AB - Pressor and tachycardic effects induced in the cat by stimulation of a lateral hypothalamic (LH) site, are shown to be mediated by sympathetic ganglia nicotinic receptor, and potentiated under atropine methyl nitrate sympathetic ganglia blockage. It is postulated that a sympatho-inhibitory pathway muscarinic ganglionic mechanism, co-activated by the LH stimulation, attenuates the pressor and tachycardic effects, the potentiation presumably being a manifestation of blockage of that mechanism. PMID- 2889614 TI - Characterization of metal binding peptides from cadmium resistant plant cells. AB - The majority of the cellular cadmium (less than 80%) in cadmium resistant Datura innoxia cells is bound to a small, metal induced peptide which is not metallothionein. This peptide consists of glutamate, cysteine and glycine in a ratio between 2:2:1 and 3:3:1 and has an apparent molecular weight of 776, under denaturing conditions. It is heat stable and complexes with cadmium to produce multimeric forms which are separable by gel filtration. Chemical analyses suggest that some amino acids are not joined by classical peptide linkages. This indicates that the synthesis of the peptide may not be directed by mRNA and that induction of its synthesis may not involve increased transcription from a putative gene corresponding directly to this peptide. A smaller proportion (greater than 15%) of the cellular cadmium is bound to a larger compound which is also heat stable and binds copper more readily than cadmium in vivo. This larger compound has an amino acid composition similar, in some respects, to metallothioneins. PMID- 2889615 TI - Identical twin marrow transplantation for 5 patients with chronic myeloid leukaemia: role of DNA finger-printing to confirm monozygosity in 3 cases. AB - 5 patients with chronic myeloid leukaemia (CML) have been treated by BMT from identical twin donors. Syngeneity of the twins was established by conventional methods in the first 2 patients. These included the similarity of phenotype, dermatoglyphics and analysis of red cell isoenzymes and blood groups. 2 of the other patients had received multiple blood transfusions prior to referral for BMT thereby invalidating red cell analysis. However genetic identity was confirmed in these patients by the method of DNA 'finger-printing' which demonstrated identical restriction-fragment length polymorphisms. Conclusive proof of syngeneity in twins prior to BMT is important since it obviates the need for T cell depletion and/or post-graft immunosuppression to prevent graft-versus-host disease (GVHD). All 5 patients were conditioned with high-dose chemoradiotherapy prior to BMT and all patients are alive and disease-free at a median follow-up of 12 months. In conclusion, we report a new, reliable method for determining syngeneity of twins which has bearing on the technical approach to BMT. PMID- 2889616 TI - Different molecular defects of G gamma (A gamma delta beta)o-thalassaemia in Thailand. AB - DNA from members of 2 Thai families with conditions considered to be delta beta thalassaemia were studied by using restriction endonuclease DNA mapping. The propositus in family A is a double heterozygote for beta-thalassaemia and delta beta-thalassaemia. DNA analysis reveals a deletion of the beta-globin gene cluster starting at the area between the Sac I and Eco RI sites near the 3' end of the G gamma-gene and extending through the A gamma-, delta- and beta-genes to an unknown extent downstream. In family B, the propositus is delta beta thalassaemia/Hb E. Deletion of the beta-globin gene cluster begins in the large intervening sequence of the A gamma-gene and removes both delta- and beta-genes downstream. PMID- 2889617 TI - [Pharmacokinetics of Cordanum]. PMID- 2889618 TI - Glutamate acting on NMDA receptors stimulates neurite outgrowth from cerebellar granule cells. AB - The effect of endogenous glutamate on neurite outgrowth from cerebellar granule cells in culture was examined. Neurite outgrowth was inhibited by enzymatic removal of endogenous glutamate from the culture medium. The broad-spectrum glutamate receptor antagonist kynurenate also inhibited neurite outgrowth from granule cells in serum-containing and serum-free cultures; the inhibition by kynurenate was reversed by exogenous glutamate. Neurite outgrowth was inhibited to the same extent by the NMDA receptor antagonist APV. These results indicate that endogenous glutamate, possibly released by granule cells themselves, stimulated neurite outgrowth through activation of the NMDA class of glutamate receptors. Activation of NMDA receptors on developing neurons may be an important mechanism for the regulation of neuronal growth and differentiation. PMID- 2889619 TI - A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. AB - A highly purified rat liver protein kinase phosphorylates and inactivates acetyl CoA carboxylase, and causes rapid inactivation of microsomal HMG-CoA reductase in the presence of MgATP. Both effects are stimulated in an identical manner by AMP, and are greatly reduced by prior treatment of the kinase with purified protein phosphatase. The dephosphorylated kinase can be reactivated in the presence of MgATP, apparently due to a distinct kinase kinase, and this reactivation is stimulated by nanomolar concentrations of palmitoyl-CoA. These results show that a common, bicyclic protein kinase cascade can potently inactivate the regulatory enzymes of both fatty acid and cholesterol biosynthesis. PMID- 2889620 TI - Epidermal growth factor as a new regulator of induction of tyrosine aminotransferase and tryptophan oxygenase by glucocorticoids. AB - Epidermal growth factor (EGF) dose-dependently enhanced the induction of tyrosine aminotransferase and tryptophan oxygenase by glucocorticoids in primary cultures of adult rat hepatocytes without itself having any effect on these enzymes in the absence of glucocorticoids. The amplifications were observed even with dexamethasone at high concentrations (10(-6) M-10(-5) M) that had a maximal effect. EGF had no effect on induction of tyrosine aminotransferase by glucagon or Bt2cAMP. The effect of EGF was also observed in adrenal-ectomized and submaxillary gland-ectomized rats. These results suggest that EGF is an endogenous amplifier of the action of glucocorticoids. PMID- 2889621 TI - Cross-reconstitution of isolated F1-ATPase from potato tuber mitochondria with F1 depleted beef heart and yeast submitochondrial particles. AB - Cross-reconstitution of isolated potato mitochondrial F1-ATPase with F1-depleted beef heart and yeast submitochondrial particles is reported. Potato F1 binds to the heterologous membrane and confers oligomycin sensitivity on the ATPase activity of the reconstituted system. Binding of F1 is promoted by the presence of Mg2+ with the maximal stimulatory effect at 20 mM. Mg2+ increase the sensitivity to oligomycin of the reconstituted system consisting of potato F1 and yeast membranes, however, they do not influence oligomycin sensitivity of potato F1 and beef heart membranes. PMID- 2889622 TI - Catalytic and noncatalytic nucleotide binding sites of chloroplast F1 ATPase. Photoaffinity labeling and peptide sequencing. AB - Exposure of chloroplast F1 ATPase to 2-azido-ATP results in the noncovalent tight binding of 2-azido-ATP or 2-azido-ADP to noncatalytic or to catalytic sites. Subsequent photolysis results in covalent labeling of adjacent tryptic peptides of the beta-subunit. Binding at noncatalytic sites results in labeling of tyrosine 385 by an ATP or an ADP moiety. Binding at catalytic sites results in labeling of tyrosine 362 by only an ADP moiety. Similar labeling patterns are observed for the heat-activated or the membrane-bound enzymes. PMID- 2889623 TI - Catalytic and noncatalytic nucleotide binding sites of the Escherichia coli F1 ATPase. Amino acid sequences of beta-subunit tryptic peptides labeled with 2 azido-ATP. AB - Under appropriate conditions tight, noncovalent binding of 2-azido-adenine nucleotides to either catalytic or noncatalytic binding sites on the E. coli F1 ATPase occurs. After removal of unbound ligands, UV-irradiation results primarily in the covalent incorporation of nucleotide moieties into the beta-subunit in both catalytic and noncatalytic site labeling experiments. Minor labeling of the alpha-subunit was also observed. After trypsin digestion and purification of the labeled peptides, microsequencing studies identified two adjacent beta-subunit tryptic peptides labeled by 2-azido-ADP or -ATP. These beta-subunit peptides were labeled on tyrosine-331 (catalytic sites) and tyrosine-354 (noncatalytic sites) in homology with the labeling patterns of the mitochondrial and chloroplast enzymes. PMID- 2889624 TI - [Experience with prophylactic work of feldsher and midwife centers]. PMID- 2889625 TI - [Deontology in the work of epidemiological health station specialists]. PMID- 2889626 TI - [Structure of the pressor reaction to angiotensin]. AB - In anesthetized rats, 1938 blood pressure (BP) responses to i.v. injections of angiotensin II were studied. 6 types and 21 subtypes of responses were distinguished: vasopressor response followed by BP normalizing (type 1; 42%) or by a transitory BP drop (type 2; 7%); BP elevation without its subsequent decrease (type 3; 3%) preliminary sharp increase of BP followed by a "classic" angiotensin pressor effect (type 4; 3%); biphasic response--a depressor response followed by a pressor one (type 5; 27%); depressor response alone (type 6; 18%). Depressor phases were increased by phentolamine and indomethacin, and were inhibited by atropine and spasmolytin. The responses to angiotensin II seem to have a vector character, cholinergic system attenuating this response. PMID- 2889627 TI - Workshop on 'optimization of influence of ovarian steroid consumption on cancer risk'. European Organization for Co-operation in Cancer Prevention Studies. PMID- 2889628 TI - Vaginal intraepithelial neoplasia. Report of 14 cases. AB - From 1978 to 1985 we have found 14 cases of vaginal intraepithelial neoplasia (VAIN) in patients previously hysterectomized. VAIN was detected by an abnormal cytology; diagnostic process included a second cytology, colposcopy, Schiller test, and directed biopsies. VAIN was classified as grade I in 5 patients (35.7%); grade II in 5 patients (35.7%); and grade III in 4 patients (28.6%). Pathogenic classification of VAIN was: VAIN de novo 9 cases (64.3%); VAIN after vaginal irradiation, 3 cases (21.4%); VAIN following incomplete removal of a cervical intraepithelial neoplasia, one case (7.1%); and VAIN as manifestation of a multicentric neoplasia of the lower genital tract, one case (7.1%). The mean time between hysterectomy and VAIN diagnosis was 6.9 years; this time was larger for those women hysterectomized by benign uterine diseases (9.0 years vs. 2.4 years). Our conclusion is that patients who have lost their uterus by malignant or benign diseases should be followed-up with periodic vaginal cytology in order to detect vaginal neoplasia in its pre-invasive stages. PMID- 2889629 TI - Uterine artery ligation to control postpartum hemorrhage. AB - Bilateral uterine artery ligation was performed for 32 patients in order to control intractable postpartum hemorrhage in 25 of them (currative ligation) and as prophylaxis against postpartum hemorrhage in seven (elective ligation). Mass ligation was used for 29 patients and isolation ligation for three. Among the 25 patients for whom curative ligation was performed, successful hemostasis was achieved in 20 patients (80%) and the technique failed in five (20%). This failure was due to a clotting defect in three and placenta previa accreta in two patients. Twenty-four patients (96%) survived and one died as a result of a clotting defect. Among five patients followed up, normal menstruation occurred with pregnancy in three of them. PMID- 2889630 TI - Outpatient diagnostic endometrial aspiration curettage with a new aspiration curette. AB - During a period of 2 years (1981-1982), 226 outpatient endometrial aspiration curettages (EACs) were performed with a new aspiration curette that had been developed by the authors. All patients had risk for general anesthesia. From 17 of them, endometrial polyps were removed by the EAC. Endometrial carcinoma was diagnosed in eight others, adenomatous hyperplasia in four, and cystic hyperplasia in two women. The main advantage of the new curette is the ability to aspirate endometrial polyps through its modified opening. PMID- 2889631 TI - Traditional obstetrics; a Nigerian experience of a traditional birth attendant training program. AB - A survey was conducted of 150 Traditional Birth Attendants (TBA) living in the peri-urban slum area of Ibadan, Oyo State, Nigeria. The purpose was to determine demographic characteristics as well as knowledge about midwifery practices prior to introducing a training program. The participants in the survey had volunteered for a free, 3-week training program in modern obstetrics. Information was collected by questionnaire which was read to the participants. The findings show that: (1) useful service is being rendered by the TBAs; (2) there are areas where the introduction of simple methods of aseptic technique, changes in some nutritional practices and increased knowledge on the benefits of immunization may improve the outcome for mothers and infants living in traditional societies in Nigeria. The findings serve as a guide for the development of content of TBA training programs. PMID- 2889632 TI - Fetal liver measurements by ultrasonography. AB - A total of 378 measurements of fetal liver size were made from 18 weeks gestation through term. Statistical analysis of the results showed a highly significant correlation between fetal liver measurements and gestational age, biparietal diameter, and fetal femur length (R = 0.93, R = 0.89, R = 0.89, respectively). Ultrasonic measurement of the fetal liver is a reliable indicator of fetal growth in the third trimester, as growth rates of the biparietal diameter and head circumference are blunt. Furthermore, consecutive measurements of fetal liver size enhance the detection of symmetrical, fetal growth, by acquisition of various ultrasonic parameters such as biparietal diameter, fetal femur length, fetal abdominal circumference and so forth. PMID- 2889633 TI - Cesarean section; changing patterns in Saudi Arabia. AB - Analysis of 8000 cesarean births in the Maternity and Children's Hospital, Riyadh, Saudi Arabia documents an increase in the cesarean section (CS) rate from 3.9% in 1979 to 9.9% in 1984. This increase is mainly attributed to indications such as repeat section (37.2%) and fetal distress (28.5%). Increase in the diagnosis of fetal distress was related to the introduction of electronic fetal monitoring and this diagnosis was not substantiated by Apgar score of the neonate. Because of the social preference for large families in Saudi Arabia, over-use of cesarean section should be avoided. For this reason, critical analysis of fetal distress and adequate trial of labor for patients with previous cesarean section is mandatory. PMID- 2889634 TI - Predisposing factors in the formation of true knots of the umbilical cord- analysis of morphometric and perinatal data. AB - Fifty-four umbilical cords with a true knot were analysed and compared to 108 normal cords. True knots were found in 1.22% of births. They occurred at a significantly higher rate in longer cords (P less than 0.00001), in male fetuses (P less than 0.05) and in multiparous women (P less than 0.003). Signs of fetal distress were observed more frequently in female fetuses, especially in those with longer cords. A true knot seems to disrupt the significant correlation (P less than 0.007) between cord length and birth weight that we observed in controls. The present study reviews the literature on the subject and suggests a possible mechanism for true knot formation. PMID- 2889635 TI - Growth retardation, size at birth and perinatal mortality in twin pregnancy. AB - The records of 194 consecutive pairs of twins were reviewed. Univariate and multivariate analyses of relative risks (RR) of perinatal death were performed. Perinatal mortality rate was higher in small-for-gestational-age twins and in fetuses with discordancy in size at birth more than 20% and 25%. The RR of perinatal death for small-for-gestational-age twins was 4.8 (2.74-8.42 95% CI). For intertwin birth-weight percent differences of 20% and 25%, the RR was 5.48 (3.2-9.38 95% CI) and 7.2 (3.87-13.42 95% CI). Population mortality attributable risk in the two populations (10.36% and 14.5%, respectively) demonstrates the importance of the prenatal assessment of the respective size of twins in preventing perinatal death. PMID- 2889637 TI - Uterine fibromyomata: presentation and management in northern Nigeria. AB - A study of uterine fibromyomata at the Ahmadu Bello University Teaching Hospital, Zaria indicates that the condition occurs in 7.8% of new gynecology cases. Infertility 87.2%, menstrual disturbance 70.4%, in association with chronic pelvic inflammatory disease 43.4%, anemia 25.0% and hypertension 25.5% were the commonest presentations. Total abdominal hysterectomy was commonly performed due to the high rate of chronic pelvic inflammatory disease. Post-operative morbidity was due to pyrexia in 28.6%, hemorrhage in 7.1% and wound infection in 6.6% of the series. PMID- 2889636 TI - Trial of labor following cesarean section--a study of 212 patients. AB - Data on the trial of labor of patients with a prior cesarean section are largely confined to studies in the First World. These results and methods may not apply to patients in developing countries. This trial studied the management of rural patients with a prior cesarean section, and tested exclusion criteria in use at the base hospital. Of those allowed a trial labor, 52% delivered vaginally. No maternal or fetal mortality occurred, and the outcome suggested a place for the controlled trial labor in selected patients. PMID- 2889638 TI - Placenta percreta with bladder involvement: case report and review of literature. AB - The authors present a very infrequent case of invasive placenta in a 33-year-old caucasian primigravida, admitted in our Department because of labor. In the course of a cesarean section performed for failure of progress, the presence of a highly adherent placenta located in the anterior part of the lower uterine segment which affected the posterior vesical wall was discovered. Recommendations for management are discussed. PMID- 2889639 TI - Formation of rat copulatory plug: purified seminal vesicle secretory proteins serve as transglutaminase substrates. AB - An in vitro system has been used to study the role of purified rat seminal vesicle proteins in the formation of the copulatory vaginal plug. Proteins II, IV (or S) and V (or F) were each separately coagulated using the transglutaminase in coagulating gland extracts. In each case the coagulum required Ca2+ ions for its formation and was insoluble in denaturing solvents. In experiments with [3H]lysine, proteins II and S incorporated [3H]lysine into glu-lys dipeptide with similar kinetics. Both the N-terminal and C-terminal glutamine residues of protein S participated in the reaction. PMID- 2889640 TI - Accumulation of free amino acids in growing Xenopus laevis oocytes. AB - The sizes of amino acid pools in growing Xenopus laevis oocytes have been measured. The total free amino acid content per oocyte increases nearly 25-fold during oocyte growth. Together, glutamic acid and aspartic acid account for approximately 59-75% of the total amino acid pool in Xenopus oocytes. On the other hand, methionine and cysteine are the least abundant of the amino acids detected, each accounting for less than 0.7% of the total pool in developing oocytes. It is argued that the acid-extractable amino acid pool represents the precursor pool used in protein synthesis. PMID- 2889642 TI - [Lipid metabolic dynamics and hormonal background during adaptation to prolonged psychoemotional and physical loads]. PMID- 2889641 TI - In vivo regulation of non-insulin-mediated and insulin-mediated glucose uptake by cortisol. AB - In vivo glucose uptake (Rd) occurs via two mechanisms: insulin-mediated glucose uptake (IMGU), which occurs in insulin-sensitive tissues, and non-insulin mediated glucose uptake (NIMGU), which occurs in both insulin-sensitive and non insulin-sensitive tissues. To determine whether these two pathways for in vivo glucose disposal are regulated independently, we studied the effect of stress levels of cortisol on IMGU and NIMGU in seven normal subjects after an overnight fast. To study NIMGU, somatostatin (SRIF, 600 micrograms/h) was infused to suppress endogenous insulin secretion and create severe insulinopenia, and glucose turnover was measured isotopically while serum glucose was clamped at approximately 200 mg/dl for 240 min. Separate studies were performed during the overnight infusion of saline or hydrocortisone (HCT; 2.0 micrograms.kg-1.min-1). The final 120 min of each study were used for data analysis. Under these conditions, insulin action is absent, and Rd = NIMGU. NIMGU was 204 +/- 11 mg/min and 208 +/- 8 mg/dl during saline and HCT, respectively (P NS). Therefore, HCT did not modulate NIMGU. To measure the effect of cortisol on Rd, hyperglycemic (200 mg/dl)-hyperinsulinemic clamp studies (30 mU.m-2. min-1) were performed during the infusion of saline or HCT. The results demonstrate that during saline infusion, steady-state rates of Rd (10.4 +/- 0.8 mg.kg-1.min-1) were achieved by 160 min; in contrast, during HCT infusion, Rd never reached steady state but increased from 4.5 +/- 0.2 in the 2nd h to 7.6 +/- 0.4 mg.kg-1.min-1 in the 4th h, P less than .01.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889643 TI - Human bile duct carcinoma cell line producing abundant mucin in vitro. AB - A human bile duct carcinoma cell line, designated OZ, was established from ascitic effusion of a patient who suffered from obstructive jaundice due to the clogging of the common bile duct with mucinous substances secreted by the cancer cells. OZ was found to be capable of producing mucin in vitro and pools of mucin were macroscopically identified on the monolayer of the cells. On the electron micrographs, cell coat type mucin and abundant intracytoplasmic desmosomes were observed. The OZ cells secreted carcinoembryonic antigen in culture and had high enzymatic activity of gamma-glutamyl transpeptidase. The tumor heterotransplanted into nude mice also showed mucin production. PMID- 2889644 TI - A restriction fragment length polymorphism in the 5' non-transcribed spacer of the rDNA of Tetrahymena thermophila inbred strains B and C3. AB - The ribosomal DNA of Tetrahymena thermophila is a 21-kb palindromic molecule which replicates autonomously in the macronuclei of this species. In addition to the rRNA coding regions, there are 5' and 3' flanking sequences which are not transcribed (non-transcribed spacer; NTS). The 5' NTS contains a bidirectional origin of DNA replication and promoter elements which direct transcription. We have identified a restriction fragment length polymorphism in the rDNA 5' NTS by comparing the B and C3 inbred strains of T. thermophila. There is a 42-bp region present in the C3 but not in the B strain rDNA; we present evidence that this difference most likely represents a deletion in the B strain rather than an insertion in the C3 strain. We also include a revised version of the nucleotide sequence of the 5' NTS DNA of inbred strain B. PMID- 2889645 TI - [Hygienic evaluation of the methods for utilizing wastes created in producing printed-circuit boards]. PMID- 2889646 TI - [Expert method of constructing a complex index of work capacity by K. K. Platonov's test]. PMID- 2889647 TI - [The use of a suprofen-benzodiazepine combination in dental sedation]. PMID- 2889649 TI - Involvement of alpha-1 and alpha-2 adrenoceptors in the postlaparotomy intestinal motor disturbances in the rat. AB - The effects of phentolamine, yohimbine and prazosin on laparotomy induced intestinal motor disturbances were studied in anaesthetised fasted rats previously equipped with electrodes, chronically implanted on the duodenum and jejunum. During continuous recording of interdigestive myoelectric activity, laparotomy under thiopental anaesthesia (Nesdonal 40 mg/kg ip) induced a primary phase of total inhibition of spiking activity lasting 26.1 +/- 1.3 min (mean +/- SE) followed by a period of disorganised activity, the first propagated migrating myoelectric complex (MMC) occurring 71.4 +/- 7.9 min after laparotomy. Phentolamine (3 mg/kg), or yohimbine (1 mg/kg) given im before laparotomy decreased by 48 and 49%, respectively, the duration of postsurgical inhibition, with a normal MMC pattern occurring immediately after. In contrast, there was only a shortening of the postlaparotomy initial inhibition of spiking activity after im prazosin (100 micrograms/kg), with a late (50-60 min) recovery of the MMC pattern. These results suggest that the initial inhibition of intestinal motility induced by laparotomy may involve alpha-1 and alpha-2 adrenoceptors, while the disruption of the MMC pattern is mainly caused by the activation of alpha-2 receptors. PMID- 2889648 TI - Sulphasalazine induced seminal abnormalities in ulcerative colitis: results of mesalazine substitution. AB - Seminal abnormalities are commonly found during sulphasalazine treatment. Although these changes appear reversible after drug withdrawal this may result in colitis relapse. Animal studies suggest that 5-aminosalicylic acid, the active component of sulphasalazine, does not impair fertility. Sixteen patients with quiescent ulcerative colitis were studied. Each patient produced three samples of semen at weekly intervals. Of the 48 samples analysed 39.6% showed oligospermia, 41.7% showed an increased number of abnormal forms and 91.7% showed impaired motility. Nine patients substituted enteric coated mesalazine (5-aminosalicylic acid) for sulphasalazine for a minimum period of three months. During this time one patient developed a salmonella associated colitis relapse; the others remained well. Improvement in sperm count (p less than 0.02), motility (p less than 0.001) and morphology (p less than 0.02) occurred in all cases. To date, four successful pregnancies have resulted, three in couples complaining of long term infertility. Treatment with enteric-coated mesalazine allows the recovery of seminal abnormalities induced by sulphasalazine in patients with colitis. PMID- 2889651 TI - Role of the BSG in the development of international gastroenterology. British Society of Gastroenterology. PMID- 2889650 TI - Increased activity of digestive enzymes in ileal enterocytes adapting to proximal small bowel resection. AB - The ability of adapting ileal enterocytes to express different digestive enzymes in their brush border membranes was tested in young female Wistar rats (n = 72) receiving 60% proximal small bowel resection. In control rats with intestinal transection both neutral aminopeptidase and alpha-glucosidase activities were shown, by quantitative cytochemistry, to increase during enterocyte migration over the lower part of the villus; thereafter enzyme activities declined or remained approximately constant. Proximal enterectomy increased the amount of alpha-glucosidase but not neutral aminopeptidase activity appearing during early enterocyte development. Thymidine labelled autoradiography showed that the rate of enterocyte migration along the ileal villus nearly doubled after jejunal resection (19.3 v 11.1 microns/h). Nevertheless, the time taken for both peptidase and saccharidase activities to appear at maximal rates in the brush border membrane was diminished by about five hours. Thus ileal enterocytes adapt to proximal small bowel resection by selective increments in enzyme expression, findings that contradict the previous hypothesis of simple metabolic immaturity. PMID- 2889652 TI - [Reconstruction in Achilles tendon rupture and simultaneous covering of a skin and soft tissue defect using the myocutaneous gastrocnemius sliding flap]. AB - A functioning Achilles tendon with soft tissue reconstruction in one stage is presented. The medial and lateral gastrocnemius musculocutaneous unit can be raised as a neurovascular sliding flap with split-thickness skin graft closure of the defect in the popliteal fossa. PMID- 2889653 TI - [RFLP in the diagnosis of disease]. PMID- 2889654 TI - [Locally applied cardioselective beta blocker and histamine provocation in patients with obstructive airway disease]. PMID- 2889655 TI - [With josamycin endogenous infection resistance is maintained. Scientific workshop on josamycin at the 15th International Congress of Chemotherapy. 23 July 1987, Istanbul]. PMID- 2889656 TI - The use of analgesics in terminal care. PMID- 2889657 TI - Pre-exposure to glucagon impairs glucose recovery after insulin-induced hypoglycemia in man. AB - The effect of a two hour period of hypo- and hyperglucagonemia on a subsequent insulin-induced hypoglycemia was studied in nine healthy volunteers. Hypoglucagonemia was provoked by somatostatin (50 micrograms/h) and hyperglucagonemia by glucagon infusion (3.25 ng/kg/min) together with somatostatin, while saline alone was given as control. Hypoglycemia was induced by insulin infusion (2.4 U/h) for two hours. The hyperglycemic effect of glucagon was transient and similar nadir glucose levels were obtained in the three experiments. Preinfusion with glucagon impaired glucose recovery in spite of preserved secretion of epinephrine during restitution of blood glucose in this experiment. It is concluded, that a period of elevated glucagon levels deteriorates the restitution of blood glucose following hypoglycemia. Hyperglucagonemia, commonly apparent in poorly controlled diabetics, may therefore be of importance in explaining the impaired recovery of blood glucose seen in such patients after hypoglycemia. PMID- 2889658 TI - Antipsychotic agents of the future. PMID- 2889659 TI - Correlation of neuroleptic dose and neurotoxicity in patients given lithium and a neuroleptic. PMID- 2889660 TI - A somatic cell hybrid panel for localizing DNA segments near the Huntington's disease gene. AB - Thirty-four random DNA probes from the terminal half of the human chromosome 4 short arm were further localized within 4pter----p15.1. A panel of somatic cell hybrid lines defining six chromosomal regions within 4pter----p15.1 was constructed using human cell lines containing translocation or deletion chromosomes. The vast majority of the DNA sequences, 32 of 34 or 94%, mapped to the three most proximal regions comprising 4p16.1----4p15.1. Only two probes were localized distal to 4p16.1: one in the region 4p16.3----4p16.1 and one in 4p16.3. D4S10, a polymorphic DNA marker linked to the Huntington's disease defect, has previously been mapped to the terminal region of 4p with conflicting assignments to 4p16.1 and 4p16.3. Analysis of restriction fragment length polymorphisms demonstrated hemizygosity for D4S10 in a patient with Wolf-Hirschhorn syndrome resulting from an unbalanced translocation t(4;8)(p16.3;p23.1), supporting the 4p16.3 localization. Our panel of somatic cell hybrids provides a rapid method for mapping new probes to the same vicinity as that of D4S10. However, the relative paucity of such DNA segments identified here suggests that a more directed approach may be required to generate additional markers near the HD gene. PMID- 2889661 TI - Chromosome-specific alpha satellite DNA from human chromosome 1: hierarchical structure and genomic organization of a polymorphic domain spanning several hundred kilobase pairs of centromeric DNA. AB - The human alpha satellite repetitive DNA family is organized as distinct chromosome-specific subsets localized to the centromeric region of each chromosome. Here, we report he isolation and characterization of cloned repeat units which define a hierarchical subset of alpha satellite on human chromosome 1. This subset is characterized by a 1.9-kb higher-order repeat unit which consists of 11 tandem approximately 171-bp alpha satellite monomer repeat units. The higher-order repeat unit is itself tandemly repeated, present in at least 100 copies at the centromeric region of chromosome 1. Using pulsed-field gel electrophoresis we estimate the total array length of these tandem sequences at the centromere of chromosome 1 to be several hundred kilobase pairs. Under conditions of high stringency, the higher-order repeat probe hybridizes specifically to chromosome 1 and can be used to detect several associated restriction fragment length DNA polymorphisms. As such, this probe may be useful for molecular and genetic analyses of the centromeric region of human chromosome 1. PMID- 2889662 TI - Genetic mapping of nine DNA markers in the q11----q22 region of the human X chromosome. AB - We have ordered nine polymorphic DNA markers within detailed map of the proximal part of the human X chromosome long arm, extending from band q11 to q22, by use of both physical mapping with a panel of rodent-human somatic hybrids and multipoint linkage analysis. Analysis of 44 families (including 17 families from the Centre d'Etude du Polymorphisme Humain) provided highly significant linkage data for both order and estimation of map distances between loci. We have obtained the following order: DXS1-DXS159-DXYS1-DXYS12-DXS3-(DXS94 , DXS178) DXYS17. The most probable location of DXYS2 is between DXS159 and DXS3, close to DXYS1 and DXYS12. The high density of markers (nine loci within 30 recombination units) and the improvement in the estimation of recombination frequencies should be very useful for multipoint mapping of disease loci in this region and for diagnostic applications. PMID- 2889663 TI - Prenatal diagnosis of X-linked chronic granulomatous disease using restriction fragment length polymorphism analysis. AB - Prenatal diagnosis of X-linked chronic granulomatous disease (CGD) was performed with restriction fragment length polymorphism (RFLP) analysis using probes flanking the gene. The male fetus and an affected male displayed the same haplotype for RFLPs belonging to six linked loci extending from DXS164 to DXS7, which encompass the CGD locus, and for which the mother was heterozygous. Diagnosis of an affected fetus was confirmed after termination of the pregnancy by the study of fetal granulocytes using the nitroblue tetrazolium reduction test. In informative families prenatal diagnosis of CGD can be made earlier by RFLP analysis than by fetal blood sampling. PMID- 2889664 TI - State of the science: methods of pain control: review of research and literature. PMID- 2889665 TI - Modulation of granulocyte functions by bacterial exotoxin and endotoxins. AB - The modulation of granulocyte functions by bacterial exotoxins (Streptolysin O, alveolysin, theta toxin) and endotoxins from salmonella and lipid A is described here. Incubation of polymorphonuclear granulocytes with thiol-activated toxins resulted in an increased leukotriene generation. Toxin-pretreated PMNs revealed an increased omega oxidation of LTB4, which may explain why toxin-stimulated cells release more LTC4 than LTB4. Furthermore, toxin-pretreated PMNs showed a decreased leukotriene generation on subsequent stimulation with the Ca-ionophore A 23187 or opsonized zymosan. PMID- 2889666 TI - Transcription of IL-2 receptor gene is stimulated by ATL-derived factor produced by HTLV-I(+) T cell lines. AB - In HTLV-I transformed T-cell lines established from the patients with adult T cell leukemia (ATL), there is a constitutive activation of the normal IL-2 receptor (IL-2-R) gene. These cell lines continuously produce an ATL-derived factor (ADF), an IL-2-R inducing factor without IL-2 activity. ADF enhances the expression of the IL-2-R through the augmentation of the IL-2-R mRNA in the HTLV I(+) T-cell line (ED) as well as the NK cell line cells (YT). In YT cells, the transcriptional initiation of the promoter of the IL-2-R gene was enhanced by ADF but not by IL-2. Production of ADF by HTLV-I(+) T-cell lines may be involved in the abnormal expression of IL-2-Rs on these cells. PMID- 2889667 TI - Enhancement of the interleukin 2 receptor expression on T cells by multiple B lymphotropic lymphokines. AB - Three new human lymphokines, interleukin-5, BSF-2 and BSF-MP6, were shown to be active in the enhancement of the IL-2 receptor expression on T cells, although they do not stimulate growth of the T cells. PMID- 2889668 TI - Interleukin-1 alpha and beta genes: linkage on chromosome 2 in the mouse. AB - Two interleukin-1 polypeptides, alpha and beta, are known, and cDNAs corresponding to each have been described. Genomic cloning and Southern blotting experiments suggest that in the mouse each is encoded by a gene present in one copy per haploid genome. Analysis of a panel of somatic cell hybrids carrying various mouse chromosomes on a constant Chinese hamster background indicates that both genes map to mouse chromosome 2. Further, analysis of the inheritance of DNA restriction fragment length polymorphisms associated with each gene in recombinant inbred strains of mice shows the two loci to be tightly linked to one another, and to lie approximately 4.7 centimorgans distal to B2m (beta-2 microglobulin). We have named the locus encoding IL-1 alpha Il-1 alpha and the locus encoding IL-1 beta Il-1b. PMID- 2889669 TI - Molecular analysis distinguishes two HLA-DR3-bearing major histocompatibility complex extended haplotypes. AB - We detected restriction fragment length polymorphisms that distinguish the extended haplotype HLA-B8,DR3,SCO1 from HLA-B18,DR3,F1C3O at the DR beta and DQ beta loci with five of seven restriction endonucleases used. One set of restriction fragments was always found on HLA-B8,DR3,SCO1 and associated with DRw52a, while the other was present on HLA-B18, DR3,F1C3O and correlated with DRw52b (the gene encoding the subtype of DRw52 associated with the BO1 or LB-Q1 antigen). Furthermore, using a full-length DQ beta gene probe, we found division in the DQw2 haplotype, in which DQw2a always associated with HLA-B8, DR3,SCO1, while DQw2b always occurred with HLA-B18,DR3,F1C3O. Our evidence thus indicates that serologically defined HLA-DR3, HLA-DRw52, and HLA-DQw2 are each produced by two structurally very different sets of genes, one set occurring in HLA-B8, DR3,SCO1, and the other in HLA-B18,DR3,F1C3O. PMID- 2889670 TI - Restriction fragment length polymorphism of DP genes defines three new DP alleles. PMID- 2889671 TI - Inhibition of in vitro generation of cytotoxicity against tumor cells by monoclonal antibody to Thy-1. AB - The Thy-1 molecule on murine T lymphocytes has been suggested to play a role in cellular activation events leading to a variety of immunologic functions. We present evidence that this molecule may be involved in signals leading to the in vitro generation of cytotoxic T cells against several tumor cell lines used as stimulators in mixed tumor-lymphocyte culture. The presence of monoclonal antibody against a polymorphic determinant on the Thy-1 molecule markedly reduced the generation of cytotoxicity after three days of culture of murine splenocytes with stimulator tumor cells bearing low levels of Ia antigen. In contrast, no effect was seen when the stimulators were either allogeneic splenocytes, or a tumor cell line expressing large amounts of Ia. These results suggest that the Thy-1 molecule is critically involved in events leading to the generation of cytotoxic effectors under some, but not all conditions. PMID- 2889672 TI - Phenothiazine poisoning. PMID- 2889673 TI - Cyproheptadine poisoning. PMID- 2889674 TI - Fluoride inhibition of proton-translocating ATPases of oral bacteria. AB - The ATPases of isolated membranes of lactic acid bacteria were found to be inhibited by fluoride in a complex manner. Among the enzymes tested, that of Streptococcus mutans GS-5 was the most sensitive to fluoride, and the initial rate of hydrolysis of ATP was reduced 50% by approximately 3 mM fluoride. The enzyme of Lactobacillus casei ATCC 4646 was the most resistant, and about 25 mM fluoride was required for 50% inhibition. The response to fluoride appeared to involve reversible, noncompetitive inhibition during short exposure to low levels of fluoride and nonreversible inhibition at higher fluoride levels. In addition, kinetic studies of the effects of fluoride on the enzymes of membranes of S. mutans and L. casei indicated that reversible inhibition was at least partly overcome at high levels of either ATP or Mg. The effects of pH on fluoride inhibition of ATPases were markedly different from the effects of pH on inhibition of acid/base regulation of intact cells by fluoride. It appeared that formation of HF was not required for inhibition of the ATPases. F1 ATPases isolated from the membranes by washing with buffers of low ionic strength proved to be less sensitive to fluoride than the membrane-associated F1F0 holoenzymes, and it was concluded that the F0 or membrane sector of the holoenzyme is involved in fluoride inhibition. PMID- 2889675 TI - Hyperprolactinemia as a marker of neurotransmitter imbalance in uremic population. AB - Serum prolactin (PRL) levels are elevated in patients with chronic renal failure (CRF) but the mechanisms responsible for these abnormalities are not fully understood. PRL secretion is undoubtedly influenced by many substances, which can be variously altered in uremia: monoamines, endogenous opiates and PTH. Our data suggest that in early renal failure PRL levels are already significantly high and the 24-h pattern of PRL secretion is significantly different from that in controls. PRL derangements could be due in mild renal failure, to unknown factors (GABA?); in severe CRF, to a major change in dopaminergic activity; in hemodialysis (HD), to a low turnover of monoamines, and in peritoneal dialysis (PD) to increased activity of serotoninergic and dopaminergic systems. PMID- 2889676 TI - Specific abnormalities of chromosome 14 in patients with acute type of adult T cell leukemia/lymphoma. AB - Chromosome analysis was performed on 1 patient with diffuse lymphoma of mixed type by histologic diagnosis and on 7 patients with the acute type of adult T cell leukemia (ATL). Specific abnormalities in chromosome 14 at break band q11 with the assigned locus of the alpha-chain gene of the T-cell antigen receptor were identified in 6 of 8 patients. Inv(14) (q11q32) was found in 2 patients and translocation of chromosome 14 at break band q11 was observed in 4. Donor chromosomes involved in translocation of the 14q11 varied, i.e., chromosomes 3, 7 or X, with the exception of one patient whose donor chromosome origin could not be determined. The breakpoint in chromosome 3 was in band p25, a region reported to include the locus of the c-raf-I oncogene. In chromosome 7, it was in band p11, a region reported to include the locus of the c-erb-B oncogene, and in the sex chromosome X, it was in band q11. One patient also had a chromosome 14 aberration at break band q32. Of the 2 remaining patients, one had lost chromosome 14 and the other had an isochromosome 14q. Our observation and other reported findings suggest that the rearrangement of chromosome 14 at break band q11 is specific for lymphoma-type or acute-type ATL patients, and aberrations of proto-oncogene expression or the coding sequence by recombination involving a T cell antigen receptor gene due to chromosome inversion or chromosome translocation may play an important role in T-cell neoplasia including ATL. PMID- 2889677 TI - Lack of correlation between rare Ha-ras alleles and urothelial cancer in Japan. AB - Restriction fragment length polymorphism (RFLP) of Ha-ras gene was surveyed by Southern blot analysis in leukocyte DNA from 55 normal individuals and 58 urothelial cancer patients in Japan. Three common alleles and 4 rare alleles were classified. The frequency of common alleles in normal Japanese individuals differed from that in Caucasians previously reported; a 7.2-7.5-kb BamHI fragment of common allele was not observed in Japanese individuals. No significant increase in frequency of the rare Ha-ras allele was observed in the group of cancer patients. Moreover, no significant difference in frequency was observed for the 3 common alleles. Tumor DNA was compared with leukocyte DNA in 30 urothelial cancer patients: in 3 of 8 cases with heterozygous Ha-ras locus, decreased intensity of one band, indicating partial loss of one allele in tumor DNA, was observed. In 3 tumors with either deletion of one Ha-ras allele or a rare Ha-ras allele, expression of Ha-ras gene was examined by Northern blot analysis. Such genetic alterations did not always result in a marked increase in Ha-ras expression. These data suggest that these genetic alterations are not directly related to Ha-ras expression, and that RFLP of Ha-ras gene is not a useful genetic marker for urothelial cancer. On the other hand, deletion of one Ha-ras allele was observed in 1 of 5 cases of bladder cancer and in 2 of 3 cases of renal pelvic cancer, suggesting that that deletion may be important in the development of urothelial cancer. PMID- 2889678 TI - Procaterol metered aerosol in patients with chronic obstructive pulmonary disease. AB - The activity and tolerability of procaterol, a recently introduced beta 2 adrenergic drug, were evaluated in comparison with fenoterol and a placebo in a single blind, cross-over study, using a metered aerosol formulation. Twelve patients suffering from chronic obstructive pulmonary disease with reversible bronchial obstruction were enrolled. Before and 30, 120, 240, 360, 480 min after drug administration, forced vital capacity (FVC), forced expiratory volume at the first second, forced expiratory flow at 25-75% and 75-85% respectively of the FVC, thoracic gas volume and the specific airways conductance were calculated. Procaterol 20 mcg showed a significant bronchodilating activity as well as fenoterol 400 mcg. This activity was already significant within 30 min, achieved its maximum after two hours and lasted more than eight hours. Side-effects were complained of by 41% of patients treated with procaterol and by 50% treated with fenoterol; procaterol showed less cardiovascular effects than fenoterol. PMID- 2889679 TI - Short-term sleep laboratory studies with cinolazepam in situational insomnia induced by traffic noise. AB - In a double-blind, placebo-controlled sleep-laboratory study the short-term effects of cinolazepam--a recently introduced 1,4 benzodiazepine with a half-life of 9 h--on the all-night sleep, morning awakening and early morning behaviour were investigated in 20 young normal subjects, whose sleep was experimentally disturbed by nocturnal traffic noise. The latter was prerecorded on tape and reproduced by loud speakers throughout the night with a sound pressure level of 68-90 dB(A) (energy equivalent mean noise level LAeq: 79dB(A)). According to the parallel group design subjects received either a placebo or 40 mg cinolazepam. Specifically, they spent nine nights in the sleep laboratory: two adaptation nights, one baseline night on placebo, three drug or placebo nights, and three post-drug/placebo nights under traffic noise. Somnopolygraphic investigations were carried out between 22h30 and 06h00. The drug was given orally half an hour before bedtime. Each 30 sec epoch was scored according to the criteria of Rechtschaffen and Kales. In the morning the subjects were awakened by 1000 Hz tones which were increased in loudness in 10 dB steps in two minute intervals. A sleep self-rating scale for sleep and awakening quality was completed half an hour after the morning toilet. Thereafter noopsychic and thymopsychic variables were evaluated utilizing a psychometric test battery. Statistical analyses of objective sleep variables demonstrated a significant improvement of sleep maintenance after 40 mg cinolazepam as reflected by an increase of sleep efficiency, decrease of wake time (during total sleep period) and number of awakenings as compared with the placebo. Sleep architecture was only affected slightly: sleep stage S1 decreased, S2 increased, while S3, S4 and SREM (S rapid eye movement) remained unchanged. Subjective sleep quality improved significantly as well. In the mornings there were no hangover signs, neither in subjective nor in objective psychometric and psychophysiological variables. Finally, the study suggests that man can adapt subjectively to nocturnal traffic noise over one week, although the improvement of objective sleep variables over time did not reach the level of statistical significance. PMID- 2889680 TI - Diagnosis and management of hirsute women. PMID- 2889681 TI - Superovulation of habitual aborters with subtle luteal phase deficiency. AB - Five habitual aborters without a known organic cause of their pregnancy losses were studied in detail by serial blood sampling for immunoreactive estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and the ratio of the two. All patients had premenstrual spotting regularly. Luteal phase progesterone levels on the 6th postovulatory day were significantly lower (11.8 +/- 1.2 ng/mL, mean +/- SEM) than in control patients (20.8 +/- 3.5 ng/mL, mean +/- SEM). Results of immunoreactive estrogen, FSH, and LH assays and the FSH/LH ratio did not reveal a discernible pattern of deviation from normal. Indirect immunofluorescence of blood samples from all habitual aborters showed evidence of autoimmunity in three of five patients without clinical symptoms of autoimmune disease. Treatment by superovulation produced at least one living child in each couple. The balance of pregnancy outcome changed from 100% abortion (N = 31) before treatment to 31% (N = 13) after treatment. These results suggest that treatment with superovulation may be the treatment of choice for habitual aborters with a subtle luteal phase deficiency. PMID- 2889682 TI - Spontaneous abortion rate in patients with endometriosis treated with progesterone. AB - Several reports suggest that women with endometriosis have a higher risk of spontaneous abortions when left untreated; however, these studies did not control for the presence of possible luteal phase defects. This study was designed to document the frequency of spontaneous abortions in women with endometriosis and ovulation defects treated prophylactically with progesterone, compared with similar patients without endometriosis. All the women had late luteal phase endometrial biopsies dating perfectly normal. Our findings show an increase in the rate of spontaneous abortions (25.7%) in women with endometriosis as compared with the entire group (3.8%). However, when the result for the group with endometriosis is compared with the subgroup of patients at diagnostic laparoscopy not showing endometriosis, the results are similar (30%). We conclude that when properly matched groups are compared, there is no increased risk of spontaneous abortions in women with endometriosis. Since we perform laparoscopies only in women failing to conceive after a reasonable number of seemingly normal cycles, the apparently high incidence of abortions in this group may be secondary to other factors that not only may lengthen the time needed for conception but also increase the abortion risk after conception. PMID- 2889683 TI - Tissue specificity and species cross-reactivity of porcine zona antigens isolated by gel filtration. AB - Antisera raised against two different doses of a major component of porcine zona pellucida isolated by gel filtration formed two precipitin lines with the components in agar double-diffusion gel. The antisera produced a positive immunofluorescence on the zona pellucida in sections of ovaries of pig, human, baboon, cow, sheep, rabbit, rat, mouse, hamster, and guinea pig. The antisera did not react with 58 different porcine tissues or five body fluids by immunofluorescence or immunodiffusion. No changes were observed in the fluorescence on the zona or in the precipitin lines when the antisera were previously absorbed with liver, erythrocytes, or plasma; however, after absorption with the porcine zona component both fluorescence and precipitin lines were completely abolished. Furthermore, control antisera against porcine erythrocyte ghosts and follicular fluid did not develop any immunofluorescence on the porcine zona. Both antisera to PZ-alpha and PZ-beta obtained by use of preparative SDS-PAGE developed the same immunofluorescence on the porcine zona shown by the antiserum to the zona component. These findings indicate that the major component of the porcine zona contains at least two zona-specific antigens, which have cross-reactivity with zona antigens of several other mammals, including humans. PMID- 2889684 TI - Thymosin alpha 1 levels in human seminal plasma and follicular fluid: implication in germ cell function. AB - High levels of thymosin alpha 1 (T alpha 1) were detected in human seminal plasma and follicular fluid. In the seminal plasma of 19 males studies, T alpha 1 levels varied from 614 to 2,604 pg/mL (mean +/- SD, 1,682.4 +/- 453.9 pg/mL). There was a correlation between the T alpha 1 levels and the total number of sperm in the ejaculate (r = .18) and seminal volume (r = .26). The infertile males, who had low levels of T alpha 1 also demonstrated fewer sperm, reduced motility, and lower semen volume. In follicular fluid collected from 24 follicles of 10 infertile females, T alpha 1 levels varied from 1,019 to 6,384 pg/mL (mean +/- SD, 3,572.8 +/- 1,599.7 pg/mL), which were higher when compared with the corresponding serum levels (mean +/- SD, 1,666.9 +/- 1,378.9 pg/mL). T alpha 1 levels present in follicular fluids which had "immature" oocytes were lower when compared with follicular fluids which had "intermediate" or "mature" oocytes. The immunoreactive T alpha 1 present in seminal plasma of males and in the follicular fluids of females may be involved in some aspect of germ cell maturation and function. The measurement of T alpha 1 levels may be useful in the diagnosis and treatment of male and female infertility, and also as a novel marker for the assessment of maturity of oocytes required for in vitro fertilization-embryo transfer. PMID- 2889685 TI - Testicular enzymes as a marker of development in human fetus. AB - The activities of different testicular enzymes, as a marker of development, have been determined at various gestational ages. The enzyme sorbitol dehydrogenase shows peak activity between 25 and 28 weeks of gestation, whereas the peak of hyaluronidase was observed between 14 and 16 weeks of gestation. The activities of pentose phosphate enzymes, such as glucose-6-phosphate dehydrogenase and transketolase in developing human fetus reach the highest level between 25 and 28 weeks and 21 and 24 weeks of gestation, respectively, indicating the most actively synthesizing period of the fetus for providing NADPH and ribose-5 phosphate for steroidogenesis and nucleotide and nucleic acid synthesis. PMID- 2889686 TI - Effect of luteinizing hormone-releasing hormone on ovulation, mating and conception in androgen-sterilized rats. AB - Attempts were made to induce pregnancy in androgen-sterilized rats. Because it is known that the preovulatory LH surge is absent in androgen-sterilized rats, a classical approach was taken to circumvent the probable deficit in cyclic release of LH by giving a subcutaneous injection of LH-RH (400 ng) every four days. Cyclic injection of LH-RH induced a regular estrus cycle in the greater part of treated females, whereas a saline-treated control group showed a persistent estrous smear. The number of eggs recovered and the mating rate increased with subsequent treatment with LH-RH, indicating a priming effect by the initial injection. However, when mated animals were autopsied on day 10 (sperm = day 1), no pregnancies had occurred. When a pituitary gland was transplanted from a normal rat into the kidney capsule of an androgen-sterilized rat in order to maintain functional corpora lutea, implantation occurred in 38% of the group of females treated with five separate LH-RH injections. Endometrial trauma in androgen-sterilized rats elicited a better response in the group which received multiple LH-RH injections than the group which received a single injection. These results indicate that the cyclic LH surge may be a necessary factor for induction of pregnancy in androgen-sterilized rats. PMID- 2889687 TI - Neurogenic involvement in follicular development and ovulation--a probability. AB - A combination of histofluorescence and histochemical and ultrastructural methods revealed the architecture of adrenergic and acetylcholinesterase (AChE) containing structures in pregnant and non-pregnant rat ovary. Besides vascular innervation, cholinergic and adrenergic nerves ran in paths contiguous to developing follicles and innervated the interstitial glands. The granulosa cells showed nonspecific AChE activity; however, there was a significant zone of specific AChE activity present in the thecal region. It is concluded that cyclic fluctuations of hormones influence variations in number, intensity, and staining density of neuronal elements. The specificity of catecholamine fluorescence was confirmed by lack of fluorescence on reserpinization. PMID- 2889688 TI - Serum levels of gonadotropins, prolactin, and progesterone in infertile female Africans. AB - To determine the prevalence of hormonal abnormalities in infertile African women, serum levels of luteinizing hormone, follicle stimulating hormone, prolactin, and progesterone were estimated using radioimmunoassay techniques during the midluteal phase in 2,047 female partners of infertile relationships. Of the patients investigated, 1,085 (53%) had abnormal serum levels of one or more of the hormones studied. Hyperprolactinemia, found in 537 (26.2%) of the patients, was the commonest hormonal abnormality. Serum progesterone level of 3 ng/mL or below which is indicative of anovulation was found in 235 (11.5%) patients, while the value of 5 ng/mL or below, suggestive of inadequate luteal functions, was found in another 121 (5.9%) patients. Since hyperprolactinemia, anovulation, and defective luteal function are treatable endocrine disorders, routine endocrine evaluation of infertile females in African societies is suggested. PMID- 2889689 TI - Characterization of histamine receptors mediating contraction and relaxation of the ovarian follicle wall. AB - Histamine is known to be present in ovarian tissue and may play a role in the ovulation process. The effect of histamine on the follicular smooth musculature was investigated using strips from the protruding part of mature bovine follicles, mounted in vitro for registration of isometric motor activity. Histamine contracted the preparation in a concentration-dependent manner. The response was inhibited competitively by the specific H1 receptor antagonist pyrilamine while the adrenergic alpha-receptor antagonist phentolamine had no clear-cut effect. A Schild plot revealed a pA2 value of 8.81, corresponding to a mean KB value (dissociation constant for receptor-antagonist complex) of (7.5 +/- 3.2) X 10(-9) M. After potassium depolarization and blockade of the contractile H1-receptors with pyrilamine, histamine induced a concentration-dependent relaxation of the follicle wall preparation. This response could be inhibited by the H2-receptor antagonist cimetidine (which also potentiated the contractile effect in the absence of pyrilamine). The pA2 value for the cimetidine-induced inhibition was 6.25, and KB was found to be (6.5 +/- 3.0) X 10(-7) M. The beta receptor antagonist propranolol was effective only in very high concentrations. It is suggested that a possible role for histamine during follicle rupture is mediated via specific receptors in the follicular smooth musculature. PMID- 2889690 TI - The effect of jejunoileal bypass (JIB) in the obese Zucker rat on a sub-group of enteroendocrine cells. AB - The effect of jejunoileal bypass in lean and obese Zucker rats on a number of enteroendocrine cell types was investigated 5 weeks following surgery to remove 80 percent of the small bowel from continuity. The endocrine cells containing somatostatin, cholecystokinin, gastric inhibitory polypeptide, enteroglucagon and neurotensin were investigated. In control rats enteroglucagon cell number was decreased in obese compared to lean animals (5 +/- 1 vs 11 +/- 1 cells/mm). Following jejunoileal bypass the enteroglucagon cell population increased two fold in both the functional and bypassed bowel in obese rats but was not elevated in lean animals. A significant increase in the number of cholecystokinin cells in the bypassed loop of the jejunum in both lean and obese bypassed rats was observed. The cholecystokinin cell population was also markedly elevated in the functional jejunum of obese but not lean bypassed rats. Only small changes were noted in cell numbers of gastric inhibitory polypeptide, somatostatin and neurotensin containing cells, suggesting that individual cell types have specific stimuli for proliferation. Epithelial height, a measure of intestinal adaptation, was similar in lean and obese rats in both the control and bypassed states, but weight loss in obese bypassed animals was significantly greater than that of lean bypassed rats. The hyperinsulinemia of obese rats was only partially normalized by jejunoileal bypass. These data indicate that jejunoileal bypass has effects on specific enteroendocrine cells which differ between lean and obese Zucker rats, and between individual cell types.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889691 TI - Immunological, histological and biochemical assessment of brown adipose tissue activity in neonatal, control and beta-stimulant-treated adult dogs. AB - Significant levels of mitochondrial uncoupling protein were demonstrated on neonatal dog mitochondria prepared from perirenal, bladder and subcutaneous adipose tissue sites. The protein was not detected in homogenates of adipose tissue samples from the same sites in adult, control dogs. However, chronic treatment of adult dogs with a beta-stimulant (LY 79730) led to the appearance of detectable amounts of uncoupling protein in perirenal and bladder but not subcutaneous adipose tissue depots. Decreases in mean cell diameter, increases in the frequency of multilocular cells and of cytochrome oxidase and creatine kinase were also associated with the effects of treatment on dog adipose tissue. The results demonstrate the age-related decline in dog brown adipose tissue and its reversal by chronic treatment with beta-stimulant. PMID- 2889692 TI - Testicular-epididymal fusion abnormality in undescended testis. AB - In the course of 1195 operations, performed in children with cryptorchidism, the testes were studied for size, turgor and fusion with the epididymis. Inquiries were made into the reasons of fusion disorders which were conspicuously numerous. Attention is called to this not too familiar condition which seems to play an important role in the emergence of fertility disorders in men with congenital cryptorchidism. PMID- 2889693 TI - The incidence of carcinoma in situ in postpubertal undescended testis. AB - In a retrospective study of 32 adult males undergoing "preventive" orchiectomy for unilateral undescended testis the average age of the patients at the time of orchiectomy was 28.3 years (range 16-63). Macroscopically, all the testes were atrophic and there was no evidence of tumour. In all surgically removed testes histological examination showed atrophied germinative epithelium and absence of spermatogenesis. In one patient, aged 16, an obvious carcinoma in situ was identified. In another 3 patients, aged 18, 19 and 29, atypical germ cells were found. Unilateral undescended testis in postpubertal patients should be treated by orchiectomy instead of orchiopexy. PMID- 2889694 TI - Pseudomonas osteomyelitis of the foot following puncture wounds. PMID- 2889695 TI - Immunochemical evidence for an active (F1-F0)-ATPase in mycoplasmas. AB - In all Acholeplasma, Mycoplasma and Spiroplasma species tested, a protein capable of reacting with antibodies prepared against the beta subunit of the proton ATPase complex from yeast, chloroplasts and Escherichia coli was detected. The reactive protein of M. gallisepticum was found to be catalytically active, suggesting that mycoplasmas, as other bacteria, possess a proton-translocating ATPase. Characterization of the ATPase activity of M. gallisepticum indicates that this organism also possesses a Na+-stimulated ATPase activity that differs from the proton-ATPase in its pH profile and its resistance to dicyclohexylcarbodiimide (DCCD). PMID- 2889696 TI - Identification of the proton ATPase operon in Mycoplasma strain PG50 by heterologous hybridization. AB - We have identified genes for the membrane-bound [H+]ATP synthetase in Mycoplasma strain PG50. Using the Escherichia coli ATP synthetase genes as a probe in heterologous hybridization under low stringency conditions, homologous sequences were detected in restriction enzyme-cleaved DNA from Mycoplasma strain PG50. From a genomic library. An EcoRI fragment harboring most of the homologous sequences was isolated. A 669-bp region of the fragment has been sequenced. The deduced amino acid sequence of the only large open reading frame shows an overall homology of 53% to a region in the C-terminal part of the alpha subunit of the E. coli ATP synthase. The hybridization data indicates that the entire atp operon is conserved in Mycoplasma strain PG50. A similar search for the Mycoplasma strain PG50 gene corresponding to dnaA gave no result. PMID- 2889697 TI - Heterogeneity of Mycoplasma hominis as detected by a probe for atp genes. AB - Use of a plasmid containing part of the atp operon of Mycoplasma PG50 as a probe in Southern blots show that this region can be used to detect the presence of Mycoplasma species in general. DNA from 14 different strains of M. hominis was analyzed for restriction fragment length polymorphism (RFLP) by the use of the same PG50 probe. The M. hominis strains exhibit considerable polymorphism, although some groupings can be observed. These groupings are compared to those obtained for the same strains by other means. The groups are not conserved, thus further demonstrating the heterogeneity of M. hominis. PMID- 2889698 TI - Mosquito spiroplasmas from France and their ecology. AB - Spiroplasmas have been isolated previously from a number of blood-sucking arthropods, including ticks, horseflies, and deerflies. More recently, spiroplasmas were isolated from mosquitoes from the USA, France, and Taiwan. Spiroplasmas isolated from mosquitoes from France belong to at least three serogroups and are serologically different from one of the Taiwan isolates, Sp2. Our Ar 1343 strain is the prototype of a new serogroup (XIII). During 3 consecutive years (1983-85), the ecology of these spiroplasmas was studied in different biotopes near, and in, the Isere River Valley in Savoia, France. A total of 23 strains was isolated from four species or groups of mosquitoes (Aedes sticticus/vexans, Ae. cantans/annulipes, Ae. cinereus/geminus and Coquillettidia richiardii). Spiroplasmas were isolated only from female mosquitoes and only during June and July. An as yet unidentified virus was also isolated from three mosquito pools, one of which yielded spiroplasmas. Spiroplasma viruses were not detected. Antibody to our Ar 1357 isolate was found in 4 of 20 sera from cows living in the areas studied, but not in sera from wild rodents or in sera from rabbit or pigeon sentinels. Finally, preliminary results are presented on the effects of experimental infection of Ae. aegypti with the Ar 1357 isolated (serogroup XXII). PMID- 2889699 TI - New spiroplasmas from insects and flowers: isolation, ecology, and host association. AB - Eight spiroplasma strains from insects and one from spring flowers failed to react with antisera specific for any of the 11 described spiroplasma groups, with sera directed against spiroplasma Group I subgroups, or with sera directed against two unnumbered groups previously reported to occur in tabanid flies. Strains, all from Maryland, were isolated from the hemolymph of the spotted cucumber beetle Diabrotica undecimpunctata and the lampyrid beetle Ellychnia corrusca, and the guts of the cantharid beetles Cantharis bilineatus and C. carolinus. Other strains were obtained from a tabanid fly, Tabanus gladiator and from the firefly Photuris pennsylvanica in Maryland and from the mosquito Culex tritaeniorhynchus in Taiwan. An isolate from pooled Cicadulina bipunctella leafhoppers in Syria apparently represented a unique group. A single isolate from spring flowers in Oklahoma also appeared to be unrelated to existing groups or subgroups. One-way deformation tests using sera prepared against known beetle and tabanid spiroplasmas showed each of the above strains to be unique. Although these results strongly indicate that the nine strains studied are representatives of unique new spiroplasma groups, the formal designation of new groups awaits fulfillment of recently proposed criteria. PMID- 2889700 TI - Synthetic oligonucleotide probes complementary to rRNA for group- and species specific detection of mycoplasmas. AB - A variety of genetic probes has been used for the detection of pathogenic bacteria. Here we present a straightforward approach for the development of group and species-specific oligonucleotide probes complementary to mycoplasmal rRNA. These probes are useful not only for the identification of mycoplasmas in clinical specimens, but also for the detection of Mollicutes in contaminated cell cultures. Radiolabeled rDNA probes detected less than 1 x 10(3) organisms in an RNA-DNA hybridization procedure. PMID- 2889701 TI - Immunocytochemical colocalization of histamine, histidine decarboxylase, 5 hydroxytryptamine and tyrosine hydroxylase in the superior cervical ganglion of the rat. AB - The coexistence of histamine, histidine decarboxylase (the enzyme synthesizing histamine), 5-hydroxytryptamine and tyrosine hydroxylase (the rate-limiting enzyme in catecholamine synthesis), was studied in the rat superior cervical ganglion with the indirect immunofluorescence method. Possible colocalization was examined by staining consecutive sections with two different antibodies, or alternatively in the same section by eluting the first antibody with a mild solution containing potassium permanganate and sulphuric acid, and by staining the same section with another antibody. It was shown that tyrosine hydroxylase immunoreactivity was found both in large principal nerve cells and in small cells, which on the basis of their size and high nucleus-cytoplasm ratio corresponded to small intensely fluorescent (SIF) cells. Histamine, histidine decarboxylase and 5-hydroxytryptamine immunoreactivities were observed only in SIF cells. Those SIF cells which were immunoreactive for histamine, histidine decarboxylase or 5-hydroxytryptamine also contained tyrosine hydroxylase immunoreactivity. On the other hand, all tyrosine hydroxylase-immunoreactive SIF cells were also immunoreactive for histidine decarboxylase or 5 hydroxytryptamine. Some of the SIF cells, which were non-reactive for histamine, were immunoreactive for tyrosine hydroxylase. PMID- 2889703 TI - Migraine headache: a call for humane treatment. PMID- 2889702 TI - Cytochemistry of gamma-glutamyltransferase in haemic cells and malignancies. AB - An improved cytochemical method for the demonstration of gamma glutamyltransferase is described. The enzyme was demonstrated in almost all normal leucocytes and in platelets. There was markedly reduced activity in most lymphoproliferative disorders. In a single case of Hodgkin's disease, T lymphocytes showed slight to moderate activity contrasting with the marked activity displayed by Reed-Sternberg cells. The plasma cells of multiple myeloma and plasma cell leukaemia showed activity equal to or stronger than that of their normal counterparts. In acute myeloid leukaemia the positivity varied widely in blast cells, but was consistently increased in monoblasts of acute monoblastic leukaemia. gamma-Glutamyltransferase may serve as a differentiation marker in the study of granulocytic and lymphocytic cell lineages. PMID- 2889704 TI - Viewbox. Duplicated collecting system with atrophic lower pole moiety. PMID- 2889705 TI - Carcinoma arising in an ileostomy. PMID- 2889707 TI - A firm grasp of the big picture. PMID- 2889706 TI - How much do you know about the new Illinois Medical Practice Act? PMID- 2889708 TI - An accomplishment that remains incomplete. PMID- 2889709 TI - The Illinois Medical Licensing Board. PMID- 2889711 TI - The Physician Disciplinary Data Bank. PMID- 2889710 TI - A fresh approach to discipline. PMID- 2889712 TI - Urinary bladder rupture in a two-year-old horse: sequel to a surgically repaired neonatal injury. AB - After routine cryptorchid castration, a 2-year-old Thoroughbred colt was admitted 72 hours later because of depression, abdominal distention, and pollakiuria, with production of small quantities of urine. A diagnosis of a ruptured bladder was made on the basis of a large volume of abdominal fluid and a disparity between the urea nitrogen and creatinine concentrations in the serum (70 mg/dl and 8.4 mg/dl, respectively) and in the abdominal fluid (154 mg/dl and 43 mg/dl, respectively). The colt had undergone surgical correction of a ruptured urinary bladder at 4 days of age, and a 5-cm tear through one of the previous scars was identified and repaired during exploratory celiotomy. The previous injury to the bladder was extensive and may have left an inherent weakness in the bladder wall. Evidence of adhesion formation or urethral obstruction was not found. The combination of a full bladder and the trauma associated with induction of anesthesia may have contributed to the recurrence of bladder rupture. PMID- 2889713 TI - Transformation of human leukocytes by co-cultivation with HTLV-1-associated myelopathy patients' leukocytes. AB - Sera and cerebrospinal fluid (CSF) from patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM) were analyzed by Western blotting, and normal human leukocytes were transformed by co-cultivation with HAM patients' leukocytes. The sera and CSF from all HAM patients formed specific bands with HTLV-1 viral proteins, including p19, p24, p28, p32, p40 and p53. After 2-3 weeks of co-cultivation, scattered foci of cell aggregates were noted on macrophage sheets. Surface markers of the transformed cells were OKT3(+), OKT4(+), OKT8(-), IL-2 receptor(+) and EBNA(-). Chromosome analysis showed a normal karyotype. HTLV 1 viral genome was integrated into DNA isolated from transformed cell lines. Electron microscopy revealed type C virus particles in transformed T-cell lines. These results indicate that peripheral leukocytes from HAM patients can transform HTLV-1-negative leukocytes and HAM patients have the potential to acquire adult T cell leukemia in the future. PMID- 2889714 TI - High levels of soluble interleukin 2 receptors released from human retrovirus infected cells. AB - Soluble interleukin 2 receptors (IL 2R) from human retrovirus-infected cells were analyzed. All the T cell lines integrated with human T cell lymphotropic virus (HTLV)-I and -II, or transfected with HTLV-I gag-pX gene, were found to release high levels of IL 2R constitutively. In contrast, this was not found in T cell lines in which HTLV-I was integrated but not expressed, human immunodeficiency virus (HIV)-infected T cell lines, or T cell, B cell, granulocyte and macrophage cell lines which were HTLV-I negative. These results raise the possibility that the pX-gene product might stimulate the generation of soluble IL 2R. In the sera from patients with adult T cell leukemia, large amounts of IL 2R were released, in contrast to sera from healthy carriers of HTLV-I. The molecular weight of IL 2R was determined to be about 50 KD by size-exclusion HPLC. PMID- 2889715 TI - Loss of genes on chromosome 22 in medullary thyroid carcinoma and pheochromocytoma. AB - Using polymorphic DNA markers, we compared the constitutional and tumor genotypes of patients with multiple endocrine neoplasia type 2A (MEN2 A). We found loss of constitutional heterozygosity at the D22S9 locus in one out of 9 medullary thyroid carcinomas (MTCs). No loss of heterozygosity was detected at 12 other loci in any of the MTCs tested. Loss of heterozygosity at D22S9 and/or D22S1 was also demonstrated in 2 out of 5 pheochromocytomas tested. These results suggest that loss or mutation of a gene on chromosome 22 may play an important role in tumorigenesis in MEN2A. PMID- 2889716 TI - Dose response of two synthetic human growth hormone-releasing factors on growth hormone release in heifers and pigs. AB - This study was undertaken to evaluate the biological potency of two synthetic human growth hormone-releasing factors, hGRF (1-44)NH2 and hGRF (1-29)NH2, on growth hormone (GH) release in young dairy heifers (n = 10) and pigs (n = 10). In each species, the GH response to an iv injection (0, .067, .2, .6 and 1.8 nmol.kg 1 body weight) of each peptide was evaluated in a double 5 X 5 Latin square design. In each square, there were five animals injected with either hGRF (1 44)NH2 or hGRF (1-29)NH2. Main effects were doses (n = 5) of hGRF and days (n = 5) of injection. In both species, data indicated that hGRF (1-44)NH2 and hGRF (1 29)NH2 equally stimulate GH secretion at all doses. In dairy heifers, average peak concentrations (81.7, 94.7, 84.5 and 93.7 ng.ml-1 vs 91.5, 81.0, 94.3 and 91.6 ng.ml-1) and area under the GH response curve (3,661, 4,541, 7,196 and 6,788 ng.ml-1.min vs 3,000, 3,982, 5,639 and 6,724 ng.ml-1.min) were not different (P greater than .05) between hGRF(1-44)NH2 and hGRF(1-29)NH2 at .067, .2, .6 and 1.8 nmol.kg-1, respectively. Similarly, in pigs, average peak concentrations (35.6, 38.6, 76.5 and 73.8 ng.ml-1 vs 28.7, 30.0, 41.3 and 80.8 ng.ml-1) and area under the GH curve (1,576, 1,567, 3,299 and 3,622 ng.ml-1.min vs 1,115, 1,658, 1,482 and 2,528 ng.ml-1.min) were not different (P greater than .05) between both peptides. A biphasic release of GH after hGRF (1-44)NH2 and hGRH (1-29)NH2 injection was observed at the highest dose in heifers. The GH response to hGRF injection was much more variable in pigs as compared with dairy heifers. In conclusion, hGRF (1-44)NH2 and its (1-29)NH2 fragment are equipotent in stimulating GH release in dairy heifers and pigs. PMID- 2889717 TI - Neurobiology of attention deficit disorder with hyperactivity: where have we come in 50 years? PMID- 2889718 TI - Exotoxin A of Pseudomonas aeruginosa: substitution of glutamic acid 553 with aspartic acid drastically reduces toxicity and enzymatic activity. AB - Glutamic acid 553 of Pseudomonas aeruginosa exotoxin A (ETA) has been identified by photoaffinity labeling as a residue within the NAD binding site (S.F. Carroll and R.J. Collier, J. Biol. Chem. 262:8707-8711, 1987). To explore the function of Glu-553 we used oligonucleotide-directed mutagenesis to replace this residue with Asp in cloned ETA and expressed the mutant gene in Escherichia coli K-12. ADP ribosylation activity of Asp-553 ETA in cell extracts was about 1,800-fold lower and toxicity for mouse L-M929 fibroblasts was at least 10,000-fold lower than that of the wild-type toxin. Extracts containing Asp-553 ETA inhibited the cytotoxicity of authentic ETA on L-M929 fibroblasts, suggesting that the mutant toxin competes for ETA receptors. The results indicate that Glu-553 is crucial for ADP-ribosylation activity and, consequently, cytotoxicity of ETA. Substitution or deletion of this residue may be a route to new ETA vaccines. PMID- 2889719 TI - Proton leakiness caused by cloned genes for the F0 sector of the proton translocating ATPase of Escherichia coli: requirement for F1 genes. AB - To study expression of uncG, the gene coding for the gamma subunit of the Escherichia coli proton-translocating ATPase, deletions were made in the intergenic region between uncA, the gene coding for the alpha subunit, and uncG. Two deletions which fused uncA and uncG coded for alpha-gamma fusion polypeptides which were synthesized well both in vitro and in vivo, demonstrating that uncG expression is normally controlled by nucleotides in the intergenic region. Multicopy plasmids carrying these fusion genes and the genes for the other subunits of the ATPase had a harmful effect on the growth of E. coli. The effect was overcome by N,N'-dicyclohexylcarbodiimide, indicating that the cells probably leaked protons. The deleterious effect was eliminated by making a nonpolar deletion in the upstream F0 gene uncB, or by cloning each of the uncA-uncG fusion genes onto a separate plasmid, removed from the F0 genes, thus demonstrating that the fusion genes were not primarily responsible for the proton permeability. A plasmid which carried F0 genes and the gene for the delta subunit caused deleterious proton leakiness in unc+ cells but not in cells from which the unc operon was deleted. The proton leakiness caused by these different plasmids was therefore due to the production of a leaky F0 proton channel and required the presence of F1 genes. The results support a model for ATPase assembly in which F1 genes or polypeptides are involved in the formation or opening of the F0 proton channel. PMID- 2889721 TI - Seizures following triazolam withdrawal despite benzodiazepine treatment. AB - The authors report a case of a 55-year-old man undergoing a triazolam withdrawal syndrome that was recognized and treated with high doses of benzodiazepines, but the patient nevertheless developed seizures. Reasons for the occurrence of these seizures despite treatment are discussed within the context of the differential potency that exists among benzodiazepines in binding to central and peripheral benzodiazepine receptors. PMID- 2889720 TI - Location of F plasmid transfer operon genes traC and traW and identification of the traW product. AB - As part of an analysis of the conjugative transfer genes associated with the expression of F pili by plasmid F, we have investigated the physical location of the traC and traW genes. We found that plasmid clones carrying a 2.95-kilobase EcoRI-EcoRV F transfer operon fragment were able to complement transfer of F lac traC mutants and expressed an approximately 92,000-dalton product that comigrates with TraC. We also found that traW-complementing activity was expressed from plasmids carrying a 900-base-pair SmaI-HincII fragment. The traW product was identified as an approximately 23,000-dalton protein. The two different F DNA fragments that expressed traC and traW activities do not overlap. Our data indicate that the traC gene is located in a more-tra operon promoter-proximal position than suggested on earlier maps and that traW is distal to traC. These results resolve a long-standing question concerning the relationship of traW to traC. The clones we have constructed are expected to be useful in elucidating the role of proteins TraC and TraW in F-pilus assembly. PMID- 2889722 TI - Rebound anxiety in panic disorder patients treated with shorter-acting benzodiazepines. AB - Rebound--the relative worsening of symptoms on discontinuation of treatment as compared to baseline symptoms--is distinguished from withdrawal. Case reports and a clinical study are presented to illustrate the management of patients with panic disorder who are taking short- and intermediate-acting benzodiazepines and are experiencing rebound anxiety. The authors present the results of switching over to clonazepam 48 patients with panic disorder who were experiencing rebound effects with alprazolam. Eighty-two percent (39) of the patients rated clonazepam as being "better" than alprazolam due to decreased dosing frequency and lack of interdose anxiety. The authors conclude that clonazepam can be a useful alternative to alprazolam and other short-acting benzodiazepines in the treatment of anxiety disorders. Clonazepam offers the advantage of antipanic efficacy without the relative side effect problems seen with tricyclic antidepressants and monoamine oxidase inhibitors. PMID- 2889723 TI - Withdrawal and detoxification from benzodiazepine dependence: a potential role for clonazepam. AB - Alprazolam and triazolam dependence and withdrawal may be uniquely problematic. This paper describes current clinical approaches to benzodiazepine withdrawal, with a focus on recent experience with alprazolam. The withdrawal characteristics of the triazolobenzodiazepines are discussed, and the epidemiology of benzodiazepine dependence is reviewed. Estimates of the incidence of alprazolam abuse are provided from Drug Abuse Warning Network data. The only two case reports in the literature of failure of cross tolerance between alprazolam and other benzodiazepines are noted to be open to alternative interpretations. A case is reported in which a patient was successfully detoxified with clonazepam from a very high dose of alprazolam. The author concludes that clonazepam may have a role in withdrawal from high-dose alprazolam dependence. PMID- 2889724 TI - Clonazepam: new uses and potential problems. AB - Clonazepam is a high-potency benzodiazepine labeled for use as an anticonvulsant. Increasingly, clonazepam has been used in the treatment of a variety of psychiatric disorders. The authors discuss its potential clinical applications, including (1) use as an adjunct to neuroleptics for treating psychosis, (2) management of specific psychotropic side effects, (3) alternative treatment for certain pain syndromes, and (4) a primary treatment for severe agitation, atypical psychosis, and anxiety disorders. Apparent treatment-emergent side effects including depression, disinhibition, and sexual dysfunction are also discussed. PMID- 2889725 TI - High-performance liquid chromatographic assay of transglutaminase and its application to the purification of human erythrocyte transglutaminase and platelet factor XIII. AB - A high-performance liquid chromatographic method was developed for the assay of transglutaminase [EC 2.3.2.13] activity. Casein and dansylcadaverine were used as substrates and the reaction was stopped by adding an excess amount of EGTA. Casein-bound dansylcadaverine was separated from free dansylcadaverine by high performance liquid chromatography on a TSK SW gel column on the basis of the differences in the molecular weight and hydrophobicity. The sensitivity was approximately 0.04 nmol of casein-bound dansylcadaverine in the assay mixture. With this assay method, human erythrocyte transglutaminase and platelet factor XIII were purified by successive chromatographies on DEAE-cellulose and Sephacryl S-300, which were common for both enzymes, followed by Blue Sepharose CL-6B and DEAE Bio-Gel A for erythrocyte transglutaminase or Phenyl-Sepharose CL-4B for platelet factor XIII. The purification factors and activity yields were 15,300 fold and 22% for erythrocyte transglutaminase and 43.8-fold and 33% for platelet factor XIII. PMID- 2889726 TI - Single site catalysis of the F1-ATPase from Saccharomyces cerevisiae and the effect of inorganic phosphate on it. AB - The kinetical characteristics of ATP hydrolysis by mitochondrial F1-ATPase from Saccharomyces cerevisiae (yeast) have been studied under conditions where only a single catalytic site per enzyme molecule bound ATP. Four major features were observed, that is, fast ATP binding to the enzyme, slow product release from the enzyme, an equilibrium close to unity between ATP and products on the enzyme, and promotion of ATP hydrolysis on the second addition of a large excess of ATP (cold chase). These are essentially the same as the kinetical characteristics observed for beef heart mitochondrial F1-ATPase, which were called as unisite catalysis by Grubmeyer et al. (Grubmeyer, C. et al. (1982) J. Biol. Chem. 257, 12092-12100), although the release of a hydrolysis product, Pi, from the yeast enzyme appeared to occur significantly faster than that from the beef enzyme, which resulted in a decreased extent of cold chase promotion of ATP hydrolysis of the yeast enzyme. The yeast F1-ATPase showed unisite catalysis even in the absence of Pi in the reaction mixtures, while it was reported for the beef F1-ATPase that the presence of Pi in the reaction mixture was essential for unisite catalysis (Penefsky, H.S. & Grubmeyer, C. (1984) in H+-ATPase (ATP Synthase) (Papa, S. et al., eds.) pp. 195-204, The ICSU Press). Another difference in the Pi effect on the kinetics was that ATP hydrolysis was initiated without a lag time in the absence of Pi in the case of the yeast enzyme when a 1,000-fold molar excess of ATP per enzyme molecular was mixed with the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889727 TI - Kinetic and equilibrium studies on the interaction of reduced flavoprotein D amino acid oxidase with pyridine carboxylates. AB - The equilibrium constants and the rate constants (binding and dissociation constants) between reduced D-amino acid oxidase and pyridine carboxylates were obtained at various pH values (from pH 6.0 to 8.3). The pH dependence of the constants is consistent with the previous conclusion from a resonance Raman study that pyridine carboxylates in the form of a cation protonated at the N atom can bind to the reduced enzyme, but those in the neutral form cannot bind, showing that the positive charge of cationic pyridine carboxylates interacts with the negative charge of the anionic reduced flavin in the reduced enzyme. The binding rate constants of picolinate and nicotinate in the cationic form for the reduced enzyme were quite similar to each other, but the dissociation rate constant of picolinate is several times smaller than that of nicotinate. Thus, it is concluded that the difference in affinity of picolinate and nicotinate for the reduced enzyme is derived from the difference of the dissociation rate constants. PMID- 2889728 TI - Electronegativity of aromatic amines as a basis for the development of ground state inhibitors of lysyl oxidase. AB - Benzylamine derivatives containing para substituents of differing electronegativity as well as isomers of aminomethylpyridine have been assessed for their substrate and inhibitor potentials toward lysyl oxidase. Substituted benzylamines with increasingly electronegative para substituents had the lowest KI values and thus were the most effective inhibitors of the oxidation of elastin by lysyl oxidase. The kcat values for these compounds as substrates of lysyl oxidase were also reduced with increasingly electronegative para substituents. Both the Dkcat and D(kcat/Km) kinetic isotope effects decreased with increasingly electronegative p-substituents in [alpha, alpha'-2H]benzylamines. In contrast, there was no Dkcat solvent isotope effect with [2H] H2O while the D(kcat/Km) solvent isotope effect tended to increase with increasingly electronegative p substituents. These results are consistent with the stabilization of an enzyme generated substrate carbanion and thus the retardation of substrate oxidation by electronegative substituents. Such ground state stabilization thus can result in compounds with increased potential for the inhibition of the oxidation of protein substrates of lysyl oxidase. PMID- 2889729 TI - Membrane binding characteristics of two forms of transforming growth factor-beta. AB - Cartilage-inducing factors A and B (CIF-A and CIF-B) from bovine bone have recently been identified as transforming growth factor-beta (TGF-beta) (Seyedin, S.M., Thompson, A. Y., Bentz, H., Rosen, D. M., McPherson, J. M., Conti, A., Siegel, N. R., Galluppi, G. R., and Piez, K. A. (1986) J. Biol. Chem., 261, 5693 5695) and a unique protein homologous to TGF-beta (Seyedin S. M., Segarini, P. R., Rosen, D. M., Thompson, A. Y., Bentz, H., and Graycar, J. (1987) J. Biol. Chem., 262, 1946-1949), respectively. Although the biological activities of TGF beta and CIF-B are similar, the divergence of CIF-B from the highly conserved amino acid sequence of TGF-beta prompted an investigation of its receptor binding properties. Three classes of cell surface binding components were identified. Class A has exclusive affinity for TGF-beta; class B has greater affinity for CIF B; and class C has equal affinity for both proteins. A high molecular weight component, the predominant binding species, was further characterized and shown to consist of two components that are either class B or class C. The differential binding properties of TGF-beta and CIF-B to cell surface components suggest that there are biological activities unique to each of the proteins. PMID- 2889730 TI - Nucleotide binding sites and chemical modification of the chromaffin granule proton ATPase. AB - The purified proton ATPase of chromaffin granules contains five different polypeptides denoted as subunits I to V in the order of decreasing molecular weights of 115,000, 72,000, 57,000, 39,000, and 17,000, respectively. The purified enzyme was reconstituted as a highly active proton pump, and the binding of N-ethylmaleimide and nucleotides to individual subunits was studied. N Ethylmaleimide binds to subunits I, II, and IV, but inhibition of both ATPase and proton pumping activity correlated with binding to subunit II. In the presence of ADP, the saturation curve of ATP changed from hyperbolic to a sigmoid shape, suggesting that the proton ATPase is an allosteric enzyme. Upon illumination of the purified enzyme in the presence of micromolar concentrations of 8-azido-ATP, alpha-[35S]ATP, or alpha-[32P]ATP subunits I, II, and IV were labeled. However, at concentrations of alpha-[32P]ATP below 0.1 microM, subunit II was exclusively labeled in both the purified and reconstituted enzyme. This labeling was absolutely dependent on the presence of divalent cations, like Mg2+ and Mn2+, while Ca2+, Co2+, and Zn2+ had little or no effect. About 0.2 mM Mg2+ was required to saturate the reaction even in the presence of 50 nM alpha-[32P]ATP, suggesting a specific and separate Mg2+ binding site on the enzyme. Nitrate, sulfate, and thiocyanate at 100 mM or N-ethylmaleimide and 7-chloro-4-nitrobenzo 2-oxa-1,3-diazole at 100 microM prevented the binding of the nucleotide to subunit II. The labeling of this subunit was effectively prevented by micromolar concentrations of three phosphonucleotides including those that cannot serve as substrate for the enzyme. It is concluded that a tightly bound ADP on subunit II is necessary for the activity of the enzyme. PMID- 2889731 TI - Nodulin-100 of soybean is the subunit of sucrose synthase regulated by the availability of free heme in nodules. AB - A cDNA sequence encoding a nodule-specific protein, nodulin-100, was identified among the abundant transcripts of poly(A)+ RNA from soybean nodules. Purification of nodulin-100 from the soluble fraction of nodule extract yielded an abundant protein with a subunit of approximately 90 kDa having properties of sucrose synthase (UDP-glucose:D-fructose 2-alpha-D-glucosyltransferase, EC 2.4.1.13). Nodule sucrose synthase of soybean is a tetrameric enzyme. Antibodies raised against this protein cross-reacted with the hybrid-released translation product of nodulin-100 cDNA, suggesting that nodulin-100 is the subunit of this enzyme. This was confirmed by partial DNA sequence analysis which showed 73% sequence homology at the amino acid level with maize sucrose synthase. Nodule sucrose synthase was found to dissociate rapidly into monomers in the presence of heme, suggesting that the availability of free heme may regulate the activity of this enzyme. Sucrose synthase activity increases rapidly during nodule development and declines during senescence. A model is presented which suggests that this enzyme plays a key role in maintaining the carbon economy of the nodules and the free heme may be involved in the flow of carbon to the bacteroids. As the degradation of leghemoglobin occurs during senescence, a concomitant decrease in sucrose synthase activity is observed. PMID- 2889732 TI - Purification of the N,N'-dicyclohexylcarbodiimide-binding proteolipid of a higher plant tonoplast H+-ATPase. AB - The H+-ATPase of Beta vacuolar membrane (tonoplast) comprises at least three functionally distinct subunits of Mr = 67,000, 57,000, and 16,000, respectively (Manolson, M. F., Rea, P. A., and Poole, R. J. (1985) J. Biol. Chem. 260, 12273 12279). The hydrophobic carboxyl reagent N,N'-dicyclohexylcarbodiimide (DCCD) inactivates the enzyme with pseudo-first order kinetics, and the concentration dependence of the reaction indicates that DCCD interacts with a single site on the enzyme to exert its inhibitory effect. The apparent pseudo-first order rate constant (k0) is reciprocally dependent on membrane protein concentration, which is expected if a large fraction of the DCCD partitions into the lipid phase. k0 has a nominal value of 1000 M-1 min-1 at a protein concentration of 250 micrograms/ml, although when phase partitioning is taken into account, the true, protein concentration-independent value of k0 is calculated to be about an order of magnitude lower. [14C]DCCD primarily labels the Mr = 16,000 polypeptide of native tonoplast vesicles. Binding is venturicidin-insensitive and occurs at a rate similar to the rate of enzyme inactivation, implying that inhibition is a direct result of covalent modification of the Mr = 16,000 polypeptide. Labeling of the containing Mr = 8,000 subunit of mitochondrial F0F1-ATPase is, on the other hand, faster by a factor of 5 and totally abolished by venturicidin. These results confirm that the Mr = 16,000 polypeptide which copurifies with tonoplast H+-ATPase activity is a subunit of the enzyme. Most of the DCCD-reactive Mr = 16,000 subunit is extracted from acetone:ethanol-washed tonoplast vesicles by chloroform:methanol. [14C]DCCD bound to the Mr = 16,000 polypeptide is enriched in the chloroform:methanol extract by 5-fold compared with native tonoplast and the specific activity (nmol of [14C]DCCD/mg of protein) can be increased a further 37-fold by chromatography on DEAE-Sephadex. It is concluded that the Mr = 16,000 subunit of the tonoplast H+-ATPase is a proteolipid. PMID- 2889733 TI - Isolation and reconstitution of the dicyclohexylcarbodiimide-sensitive proton pore of the clathrin-coated vesicle proton translocating complex. AB - The clathrin-coated vesicle proton translocating complex is composed of a maximum of eight polypeptides. The function of the components of this system have not been defined. Proton pumping catalyzed by the reconstituted, 200-fold purified proton translocating complex of clathrin-coated vesicles is inhibited 50% at a dicyclohexylcarbodiimide (DCCD)/protein ratio of 0.66 mumol of DCCD/mg of protein. At an identical DCCD/protein ratio, the 17-kDa component of the proton pump is labeled by [14C]DCCD. Through toluene extraction, the 17-kDa subunit has been isolated from the holoenzyme. The 17-kDa polypeptide diminished proteoliposome acidification when coreconstituted with either bacteriorhodopsin or the intact clathrin-coated vesicle proton translocating ATPase. In both instances, treatment of the 17-kDa polypeptide with DCCD restored proteoliposome acidification. Moreover, the proton-conducting activity of the 17-kDa polypeptide is abolished by trypsin digestion. These results demonstrate that the 17-kDa polypeptide present in the isolated proton ATPase of clathrin-coated vesicles is a subunit which functions as a transmembranous proton pore. PMID- 2889734 TI - Escherichia coli H+-ATPase. Glutamic acid 185 in beta subunit is essential for its structure and assembly. AB - The uncD gene for the beta subunit of Escherichia coli H+-ATPase was cloned downstream of the lac promoter and mutagenized (Glu-185----Gln or Lys) by an oligonucleotide-directed procedure. The recombinant plasmid was introduced into a strain in which the unc operon for subunits of H+-ATPase was deleted. The wild type or mutant beta subunit synthesized amounted to about 10% total cell protein and was mainly found in the cytoplasmic fraction. These subunits could be purified to almost homogeneity by conventional procedures. The wild-type and two mutant beta subunits had essentially the same Kd values for 8-anilinonaphthalene 1-sulfonate, aurovertin, and ATP, although the fluorescence intensities of 8 anilinonaphthalene-1-sulfonate and aurovertin were significantly less when bound to the two mutant beta subunits than when bound to the wild-type subunit. The three beta subunits showed essentially the same circular dichroism spectra, indicating alpha-helical contents of about 16-18%. Thus, the mutations did not cause marked change of the secondary structure of the subunit. However, measurements of theta 208 during linear increase in temperature suggested that replacement of Glu-185 by Gln or Lys slightly changed the stability of the secondary structure. Only trace amounts of alpha beta gamma complexes could be reconstituted using the two mutant beta subunits. These results suggest that Glu 185 or the region in its vicinity may be essential for subunit assembly. The methods developed in this study should be useful for further studies on the beta subunit. PMID- 2889735 TI - Mapping of nucleotide-depleted mitochondrial F1-ATPase with 2-azido-[alpha 32P]adenosine diphosphate. Evidence for two nucleotide binding sites in the beta subunit. AB - Photolabeling of nucleotide binding sites in nucleotide-depleted mitochondrial F1 has been explored with 2-azido [alpha-32P]adenosine diphosphate (2-N3[alpha-32P] ADP). Control experiments carried out in the absence of photoirradiation in a Mg2+-supplemented medium indicated the presence of one high affinity binding site and five lower affinity binding sites per F1. Similar titration curves were obtained with [3H]ADP and the photoprobe 3'-arylazido-[3H]butyryl ADP [( 3H]NAP4 ADP). Photolabeling of nucleotide-depleted F1 with 2-N3[alpha-32P]ADP resulted in ATPase inactivation, half inactivation corresponding to 0.6-0.7 mol of photoprobe covalently bound per mol F1. Only the beta subunit was photolabeled, even under conditions of high loading with 2-N3[alpha-32P]ADP. The identification of the sequences labeled with the photoprobe was achieved by chemical cleavage with cyanogen bromide and enzymatic cleavage by trypsin. Under conditions of low loading with 2-N3[alpha-32P]ADP, resulting in photolabeling of only one vacant site in F1, covalently bound radioactivity was located in a peptide fragment of the beta subunit spanning Pro-320-Met-358 identical to the fragment photolabeled in native F1 (Garin, J., Boulay, F., Issartel, J.-P., Lunardi, J., and Vignais, P. V. (1986) Biochemistry 25, 4431-4437). With a heavier load of photoprobe, leading to nearly 4 mol of photoprobe covalently bound per mol F1, an additional region of the beta subunit was specifically labeled, corresponding to a sequence extending from Gly-72 to Arg-83. The isolated beta subunit also displayed two binding sites for 2-N3-[alpha-32P]ADP. When F1 was first photolabeled with a low concentration of NAP4-ADP, leading to the covalent binding of 1.5 mol of NAP4 ADP/mol F1, with the bound NAP4-ADP distributed equally between the alpha and beta subunits, a subsequent photoirradiation in the presence of 2-N3[alpha 32P]ADP resulted in covalent binding of the 2-N3[alpha-32P]ADP to both alpha and beta subunits. It is concluded that each beta subunit in mitochondrial F1 contains two nucleotide binding regions, one of which belongs to the beta subunit per se, and the other to a subsite shared with a subsite located on a juxtaposed alpha subunit. Depending on the experimental conditions, the subsite located on the alpha subunit is either accessible or masked. Unmasking of the subsite in the three alpha subunits of mitochondrial F1 appears to proceed by a concerted mechanism. PMID- 2889736 TI - Tetradecanoyl phorbol acetate suppresses follicle-stimulating hormone-induced synthesis of the cholesterol side-chain cleavage enzyme complex in rat ovarian granulosa cells. AB - The effect of tetradecanoylphorbol acetate (TPA) on follicle-stimulating hormone (FSH)-induced synthesis of the cholesterol side-chain cleavage (SCC) enzyme complex was studied in rat ovarian granulosa cells cultured for 48 h in serum free medium. Cell proteins were radiolabeled with [35S]methionine, followed by immunoprecipitation of cholesterol side-chain cleavage cytochrome P-450 (P 450SCC) as well as the iron-sulfur protein adrenodoxin. Polyacrylamide gel electrophoresis and fluorography of the immunoprecipitates showed that TPA, when added in combination with FSH (50 ng/ml) or dibutyryl cAMP (Bt2cAMP; 1 mM), suppressed the stimulatory effects of these compounds on the synthesis of the SCC components in a concentration-dependent fashion. The effect of TPA was accompanied by decreased progesterone formation and decreased cAMP accumulation. The structural analog of TPA, phorbol-4 alpha-didecanoate, which does not activate protein kinase C (Ca2+/phospholipid-dependent enzyme), had no effect on the FSH- or Bt2cAMP-stimulated synthesis of SCC and progesterone or on cAMP formation. In addition to inhibiting the synthesis of these proteins, TPA greatly reduced the FSH- and Bt2cAMP-induced increase in levels of mRNA encoding the precursor form of P-450SCC. It is concluded that the effect of the phorbol ester TPA to inhibit FSH-stimulated progesterone formation in cultured ovarian granulosa cells of the rat involves decreased synthesis of the components of the SCC enzyme complex due to reduced levels of mRNA encoding the precursor forms of these proteins. The results are indicative that TPA not only inhibits FSH mediated stimulation of cAMP formation but also may block cAMP-mediated induction of SCC synthesis. It is postulated that the effects of TPA may reflect the physiological role of protein kinase C in the regulation of ovarian steroidogenesis. PMID- 2889737 TI - The radial forearm flap in burn reconstruction. PMID- 2889738 TI - Cold injury: a collective review. AB - Cold injury remains a crippling problem. Although research is opening new avenues of accurate diagnosis and expeditious treatment, the gold standard against which these methods must be measured continues to be conservative treatment. PMID- 2889739 TI - Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites. AB - Pulse-chase experiments have revealed that cyclin, the auxiliary protein of DNA polymerase-delta, is stable during the transition from growth to quiescence in 3T3 cells. Immunoblotting together with immunofluorescence analysis has shown that the amount of cyclin after 24 h of quiescence is 30-40% of that of growing cells and that it presents a nucleoplasmic staining. Immunofluorescence studies show the existence of two populations of cyclin during the S phase, one that is nucleoplasmic as in quiescent cells and is easily extracted by detergent, and another that is associated to specific nuclear structures. By using antibromodeoxyuridine immunofluorescence to detect the sites of DNA synthesis, it was shown that the staining patterns of the replicon clusters and their order of appearance throughout the S phase are identical to those observed for cyclin. Two dimensional gel analysis of Triton-extracted cells show that 20-30% of cyclin remains associated with the replicon clusters. This population of cyclin could not be released from the nucleus using high-salt extractions. This demonstrates that cyclin is tightly associated to the sites of DNA replication and that it must have a fundamental role in DNA synthesis in eukaryotic cells. PMID- 2889741 TI - High lateral mobility of endogenous and transfected alkaline phosphatase: a phosphatidylinositol-anchored membrane protein. AB - The lateral mobility of alkaline phosphatase (AP) in the plasma membrane of osteoblastic and nonosteoblastic cells was estimated by fluorescence redistribution after photobleaching in embryonic and in tumor cells, in cells that express AP naturally, and in cells transfected with an expression vector containing AP cDNA. The diffusion coefficient (D) and the mobile fraction, estimated from the percent recovery (%R), were found to be cell-type dependent ranging from (0.58 +/- 0.16) X 10(-9) cm2s-1 and 73.3 +/- 10.5 in rat osteosarcoma cells ROS 17/2.8 to (1.77 +/- 0.51) X 10(-9) cm2s-1 and 82.8 +/- 2.5 in rat osteosarcoma cells UMR106. Similar values of D greater than or equal to 10(-9) cm2s-1 with approximately 80% recovery were also found in fetal rat calvaria cells, transfected skin fibroblasts, and transfected AP-negative osteosarcoma cells ROS 25/1. These values of D are many times greater than "typical" values for membrane proteins, coming close to those of membrane lipid in fetal rat calvaria and ROS 17/2.8 cells (D = [4(-5)] X 10(-9) cm2s-1 with 75 80% recovery), estimated with the hexadecanoyl aminofluorescein probe. In all cell types, phosphatidylinositol (PI)-specific phospholipase C released 60-90% of native and transfection-expressed AP, demonstrating that, as in other tissue types, AP in these cells is anchored in the membrane via a linkage to PI. These results indicate that the transfected cells used in this study possess the machinery for AP insertion into the membrane and its binding to PI. The fast AP mobility appears to be an intrinsic property of the way the protein is anchored in the membrane, a conclusion with general implications for the understanding of the slow diffusion of other membrane proteins. PMID- 2889740 TI - Structure of the novel membrane-coating material in proton-secreting epithelial cells and identification as an H+ATPase. AB - Specialized proton-secreting cells known collectively as mitochondria-rich cells are found in a variety of transporting epithelia, including the kidney collecting duct (intercalated cells) and toad and turtle urinary bladders. These cells contain a population of characteristic tubulovesicles that are believed to be involved in the shuttling of proton pumps (H+ATPase) to and from the plasma membrane. These transporting vesicles have a dense, studlike material coating the cytoplasmic face of their limiting membranes and similar studs are also found beneath parts of the plasma membrane. We have recently shown that this membrane coat does not contain clathrin. The present study was performed to determine the structure of this coat in rapidly frozen and freeze-dried tissue, and to determine whether the coat contains a major membrane protein transported by these vesicles, a proton pumping H+ATPase. The structure of the coat was examined in proton-secreting, mitochondria-rich cells from toad urinary bladder epithelium by rapidly freezing portions of apical membrane and associated cytoplasm that were sheared away from the remainder of the cell using polylysine-coated coverslips. Regions of the underside of these apical membranes as large as 0.2 micron2 were decorated by studlike projections that were arranged into regular hexagonal arrays. Individual studs had a diameter of 9.5 nm and appeared to be composed of multiple subunits arranged around a central depression, possibly representing a channel. The studs had a density of approximately 16,800 per micron2 of membrane. Similar arrays of studs were also found on vesicles trapped in the residual band of cytoplasm that remained attached to the underside of the plasma membrane, but none were seen in adjacent granular cells. To determine whether these arrays of studs contained H+ATPase molecules, we examined a preparation of affinity purified bovine medullary H+ATPase, using the same technique, after incorporation of the protein eluted from a monoclonal antibody affinity column into phospholipid liposomes. The affinity-purified protein was shown to be capable of ATP-dependent acidification. In such preparations, large paracrystalline arrays of studs identical in appearance to those seen in situ were found. The dimensions of the studs as well as the number per square micrometer of membrane were identical to those of toad bladder mitochondria-rich cells: 9.5 nm in diameter, 16,770 per micron2 of membrane.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2889743 TI - Assay for tyrosine hydroxylase in hypothalamic homogenates using high-performance liquid chromatography with electrochemical detection. AB - A highly sensitive and reliable assay for tyrosine hydroxylase (TH) activity in hypothalamic homogenates of male rats using high-performance liquid chromatography with electrochemical detection is described. Modification of sample preparation and chromatographic conditions led to a complete separation of L-3,4-dihydroxyphenylalanine (L-DOPA) and alpha-methyldopa from all interfering catecholamines and their metabolites. This assay is highly sensitive; 2 pmol of L DOPA formed enzymatically could be measured. We were able to determine TH activity in tissue pieces weighing less than 1 mg. TH activity was not changed after storage for three months at -80 degrees C. In hypothalamic homogenates the Michaelis constant (KM) for L-tyrosine was 80.5 +/- 6.5 mumol/l and the maximal velocity (Vmax) was 132.5 +/- 10.5 pmol/mg of protein per min for L-DOPA formed enzymatically. PMID- 2889742 TI - Localizing the subunit pool for the temporally regulated polar pili of Caulobacter crescentus. AB - The pili of the stalked bacterium Caulobacter crescentus are assembled at a specific time in the life cycle at one pole of the cell and are composed of the monomer protein, pilin. A previous study demonstrated that the onset of pilin synthesis occurs well before pili appear on the surface, suggesting that pilin accumulates within the cell. In the present study, an electron microscope immunocytochemistry assay was used to determine the subcellular location of this unassembled pilin and its fate during pilus assembly and cell division. Populations of synchronously growing cells were embedded in epoxy resin at selected times during the cell cycle. Ultrathin sections were treated with pilin specific antibody, followed by protein A coupled to colloidal gold. It was determined that the cellular location for unassembled pilin was the cell cytoplasm. All cell membranes and regions of nuclear material were poorly labeled. Quantitation demonstrated that label density increased during the period of pilin synthesis and declined during the period of pilus assembly and maintenance. The pilin pool was not unequally segregated at division; e.g., to the daughter cell that is elaborating pili. Mutants which have simultaneously lost the ability to produce flagella, pili, and other polar organelles, possibly due to alterations in the specialized region of polar organelle assembly, were also examined by the immunocytochemistry technique. There was no significant difference in the pilin pool size relative to the wild type, indicating that pilin synthesis continues in the absence of a functioning assembly site. This pattern of synthesis and assembly for the pilus is significantly different from that of the polar flagellum which is produced at the same time and location on the cell surface. These findings are discussed in relation to the hypothesized organization center at the cell pole which may have a major role in directing the assembly of all the polar structures. PMID- 2889744 TI - Determination of timelotem dihydrogenmaleate and its main metabolite N desmethyltimelotem in plasma by capillary gas chromatography. PMID- 2889745 TI - Determination of duoperone in plasma by high-performance liquid chromatography. PMID- 2889746 TI - Determination of fentanyl and alfentanil in plasma by high-performance liquid chromatography with ultraviolet detection. PMID- 2889747 TI - Determination of azelastine and desmethylazelastine in human plasma by high performance liquid chromatography. AB - A manual-injection liquid chromatographic method using fluorescence detection permitted determination of a new antiasthmatic drug, azelastine, and its desmethyl metabolite extracted from human plasma. Reliable quantitation was achieved to at least 0.3 ng/ml for each analyte. No interference was seen in co chromatography of sixteen other substances, which were potential co-medications (or their metabolites) as used in standard asthma or allergy treatment. PMID- 2889748 TI - Shrinking of a growth hormone-producing pituitary tumor by continuous subcutaneous infusion of the somatostatin analog SMS 201-995. AB - SMS 201-995, a long-acting somatostatin analog, was given as the initial treatment to an acromegalic patient. SMS 201-995 (200 micrograms, sc, three times daily) reduced, but did not normalize, serum GH levels. Complete and prolonged control of GH secretion was obtained with a 600-micrograms daily continuous sc infusion (CSI), and the patient was treated in this way for 6 months. Rapid improvement of clinical signs and symptoms of acromegaly occurred, as did major tumor shrinkage. The other pituitary functions did not change. After 6 months, the daily SMS 201-995 dose was progressively reduced; GH secretion remained suppressed. After 12 months of treatment, GH secretion was controlled with a CSI of 100 micrograms SMS 201-995 daily, but not with two daily sc 100-micrograms injections. Further significant reduction in tumor size occurred. We conclude that CSI of SMS 201-995 resulted in constant GH normalization and marked clinical and morphological improvement. This form of treatment should be considered as an alternative to ablative treatment of acromegaly. PMID- 2889749 TI - Effects of alpha 1-adrenergic blockade on pulsatile luteinizing hormone, follicle stimulating hormone, and prolactin secretion in polycystic ovary syndrome. AB - Central noradrenergic mechanisms may participate in the regulation of pulsatile gonadotropin secretion in women with the polycystic ovary syndrome (PCO). To examine this possibility we measured serum LH, FSH, and PRL concentrations at 10 min intervals and total testosterone and 17 beta-estradiol at 60-min intervals for 8 h basally and during the infusion of the alpha 1-adrenoceptor antagonist thymoxamine (10 micrograms/kg X min) in 10 young women with PCO. Mean and integrated serum LH concentrations as well as LH pulse frequency were not significantly altered (P = NS) during the thymoxamine infusion. However, we found an increase in LH pulse amplitude as both net (P less than 0.002) and percent (P less than 0.002) increment, as well as mean LH peak values (P less than 0.05) during alpha 1-adrenergic blockade. There were no significant changes in pulsatile FSH and PRL secretion or gonadal sex steroids during these experimental conditions. These data suggest that in PCO patients, 1) brain noradrenergic mechanisms do not play a stimulatory role in regulating the frequency of pulsatile LH secretion, 2) central noradrenergic activity inhibits LH pulse amplitude, and 3) PRL and FSH pulsatility are not altered by central noradrenergic blockade. PMID- 2889750 TI - Differential alterations of the circulating prosomatostatin-derived peptides during insulin-induced hypoglycemia in man. AB - Insulin-induced hypoglycemia stimulates a rise of somatostatin-like immunoreactivity (SLI) in the venous circulation of man. Plasma SLI is comprised of a heterogenous group of peptides including somatostatin-28 (SS-28) somatostatin-28-(15-28), somatostatin-28-(16-28), and prosomatostatin (Pro-SS). To determine which of these Pro-SS related peptides is released after hypoglycemia, we developed an immunoadsorption method that rapidly and accurately separates SS-28 from the other somatostatins. This method involves the selective retention of SS-28 on a conjugate of agarose with immunoglobulins that recognize an epitope in the NH2-terminal region of SS-28. Pro-SS, SS-28-(15-28), SS-28-(16 28), henceforth referred to collectively as SS-28-(15-28), and SS-28, once separated, were then analyzed by RIA with a COOH-terminal antibody. Ten normal men were studied after an overnight fast. Pork insulin (0.05 U/kg) was injected iv, and blood was collected before and after the onset of hypoglycemia. The mean basal SS-28-(15-28) level was 13 +/- 1 (+/- SEM) pg/mL, and the mean basal SS-28 levels were 19 +/- 3 (+/- SEM) pg/mL. Plasma SS-28-(15-28) did not increase after insulin administration, but the mean SS-28 level increased by 76% (P less than 0.01). We propose that the release of SS-28, presumably from the gastrointestinal tract, during hypoglycemia occurs as a result of activation of the autonomic nervous system and speculate that SS-28, because of its ability to inhibit insulin secretion, may be important in counterregulation during glucopenia. PMID- 2889751 TI - Puncture wound osteochondritis of the foot caused by CDC group Vd. AB - A case of puncture wound osteochondritis of the foot caused by CDC group Vd is presented because of the unusual nature of the infecting organism. This organism may be confused with Pseudomonas aeruginosa, the usual pathogen responsible for this type of infection, but does not have a similar antimicrobial susceptibility profile. For this reason, it is important to obtain appropriate culture specimens and to identify and test the susceptibility of bacterial isolates from cases of puncture wound-associated osteochondritis so that optimal therapeutic regimens can be determined. PMID- 2889752 TI - Retroviruses and human disease. AB - Over the past 25 years animal retroviruses have been favoured subjects of research by virologists, oncologists, and molecular biologists. Retroviruses have given us reverse transcriptase, oncogenes, and cloning vectors that may one day be exploited for human gene therapy. They have also given us leukaemia and the acquired immune deficiency syndrome (AIDS). Kawasaki disease and tropical spastic paraparesis are thought to be associated with retrovirus infection, and other diseases such as de Quervain's thyroiditis, multiple sclerosis, acquired hypogammaglobulinaemia, and certain forms of non-A, non-B hepatitis have come under passing suspicion of a retroviral aetiology. With AIDS threatening to become pandemic, and a second AIDS virus appearing in West Africa, human retroviruses are under intensive study for new antiviral drugs targeted to their unique mode of replication, and for the development of vaccines. PMID- 2889754 TI - Glycine: an alternative transmitter candidate of the pallidosubthalamic projection neurons in the rat. AB - Autoradiographic retrograde tracing techniques with radioactive transmitters were used to analyse the identity of a putative transmitter in the rat pallidosubthalamic (GP-STN) pathway. One to 2 hours after the stereotaxic injection of 3H-glycine restricted to the STN, a large number of neuronal somata were radiolabeled in the GP. No comparable labeling was observed following the injection of 3H-gamma-aminobutyric acid (3H-GABA) into the same nucleus even with survival times as long as 6 hours. Specifically, no significant somatic labeling was detected either in the GP or in the caudoputamen (CPU). Only when 3H-GABA was injected into the substantia nigra did CPU and GP neurons become labeled. On the contrary, STN neuronal somata were invariably labeled 6 hours after the intrapallidal injection of 3H-GABA, whereas no perikaryal labeling was observed in the STN after 3H-glycine injection into the GP. The perikaryal labeling was prevented in all cases by intraventricular administration of colchicine 1 day before the isotope injections. The observations suggest that 3H-glycine was preferentially transported retrogradely through the GP-STN pathway, and 3H-GABA through the STN-GP projection. In view of the recent controversy on the role of GABA as a putative transmitter of the GP-STN projection, we now propose glycine as an alternative transmitter candidate of these critically situated neurons in the basal ganglia. PMID- 2889753 TI - Haemophilia A: carrier detection and prenatal diagnosis by linkage analysis using DNA polymorphism. AB - Restriction fragment length polymorphisms (RFLPs) within or close to the factor VIII locus are very useful for genetic linkage analysis. Such RFLPs allow a mutant allele to be tracked in a family, segregating haemophilia A even when, as is usually the case, the precise mutation causing failure to synthesise factor VIII is unknown. To date two markers tightly linked to the factor VIII locus have been described, one of which is highly polymorphic and therefore informative in most kindreds. A significant crossover rate, however, does not make diagnosis absolute. Three intragenic RFLPs have been defined, which, taken together, are informative in about 70% of women, providing virtually deterministic genetic diagnosis. PMID- 2889755 TI - Localization of tyrosine hydroxylase-immunoreactive neurons in the cat hypothalamus, with special reference to fluorescence histochemistry. AB - The present study examines the distribution and morphological characteristics of neurons containing immunoreactivity of tyrosine hydroxylase in the cat hypothalamus. We used the indirect immunoperoxidase technique on vibratome sections. Tyrosine hydroxylase-immunoreactive cell bodies were widely distributed in discrete regions of the cat hypothalamus. Several principal cell groups were identified. They were seen in the posterior and dorsal hypothalamic areas, zona incerta, dorsomedial and lateral hypothalamic areas, arcuate nucleus, periventricular nucleus, paraventricular nucleus, and an area of the tuber cinereum and preoptic area. These cells presented two different morphological characteristics; small with two to three short processes and medium to large, multipolar with three to five long dendritic trees. The atlas is presented in twelve cross-sectional drawings of the cat hypothalamus from the level A8.5 to A15 of the Horsley-Clarke stereotaxic planes. We also examined the distribution of hypothalamic catecholamine fluorescent neurons by using the aqueous aldehyde method in combination with glyoxylic acid applied to vibratome sectioned tissues, which improves sensitivity. Comments are made on the relative localizations of the tyrosine hydroxylase-immunoreactive and aldehyde-induced histofluorescent cells, as well as on species differences between the cat, rat, and mouse. PMID- 2889756 TI - Lymphomatoid papulosis. A follow-up study of 30 patients. AB - Thirty patients, 13 female and 17 male, have been followed from 3 months to 22 years (mean, 81 months; median, 63 months) and special studies have been performed on a proportion of these in order to try to predict malignant evolution. Age at onset was from 20 to 70 years (mean, 43 years; median, 42 years). Duration of disease was from 1 to 30 years (mean, 119 months; median 161 months). Seven patients also had parapsoriasis en plaque or plaque-stage mycosis fungoides at the time of diagnosis and one patient had erythroderma. None of the 22 uncomplicated lymphomatoid papulosis patients developed malignant cutaneous lymphoma during the period of observation, while the remaining 8 patients who had concurrent parapsoriasis en plaque, mycosis fungoides, or erythroderma did not deteriorate further. Single-cell deoxyribonucleic acid (DNA) measurements on the dermal infiltrate were done in 13 patients and were abnormal in 7 patients. Two of these had greatly abnormal DNA histograms and at the same time an abnormal clinical presentation with multiple nodules and tumors. The remaining five patients had DNA histograms that indicated a potential for malignancy. Monoclonal antibody studies were performed on skin biopsy specimens of 10 patients. The dermal infiltrate was dominated by T-helper lymphocytes and some Hodgkin and Reed Sternberg cells could be detected by the antibodies Ki-1, Ki-24, and Ki-27. Human T-lymphotropic virus type I (HTLV-I) antibodies were found in 3 of 18 patients examined. Treatment with psoralens plus ultraviolet A (PUVA) was effective (partial or complete remission) in six patients but they relapsed at cessation of therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889757 TI - [Comparison of the efficacy of analgesics in pain after oral surgery]. PMID- 2889758 TI - The Thrombolysis in Myocardial Infarction (TIMI) phase II pilot study: tissue plasminogen activator followed by percutaneous transluminal coronary angioplasty. AB - The Thrombolysis in Myocardial Infarction (TIMI) Study Group is investigating whether percutaneous transluminal coronary angioplasty or intravenous beta receptor blockers, or both, are useful adjuncts to recombinant tissue-type plasminogen activator (rt-PA) in the treatment of patients with acute myocardial infarction (TIMI II study). A total of 317 patients with acute myocardial infarction were treated an average of 2.7 hours after the onset of chest pain during the course of a nonrandomized pilot investigation with 150 mg of rt-PA given over 6 hours. This dose of rt-PA resulted in a high rate of infarct-related coronary artery patency (82 and 87% of patients catheterized an average of either 1 or 32 hours after entry, respectively) and a low 21 day mortality rate of 4.4%. Coronary angioplasty was performed successfully in greater than 90% of patients with appropriate anatomy and in greater than 50% of those treated with rt-PA. In 75 patients treated within 2 hours of the onset of chest pain only 2 (2.7%) were dead by 6 weeks. However, five cases of intracranial hemorrhage were noted, and the rt-PA dose was subsequently reduced to 100 mg given over 6 hours. The TIMI II design and the results of the TIMI II pilot study are discussed. PMID- 2889759 TI - Antidepressant withdrawal syndromes: phenomenology and pathophysiology. PMID- 2889760 TI - Anticholinergic equivalents and parkinsonism: a model for predicting side-effects of antipsychotic drugs. AB - The tendency of antipsychotics to produce extrapyramidal side-effects varies inversely with their antimuscarinic activity. This paper reviews the antipsychotic and antimuscarinic potency of these drugs and compares the total antimuscarinic activity in standard daily doses of antipsychotics, antiparkinson agents and antidepressants. The authors examine factors associated with tolerance of benztropine withdrawal in 39 inpatients. Patients with serious EPS relapse after benztropine withdrawal had an excess of antipsychotic over antimuscarinic activity in their remaining medications. The results suggest an optimal ratio between total antipsychotic and anticholinergic doses, and a simple model for predicting antiparkinson drug requirements. PMID- 2889761 TI - An open clinical trial of fenfluramine in chronic schizophrenia: a pilot study. AB - The reports of hyperserotonaemia in chronic schizophrenics and the indications that fenfluramine, a serotonin-releasing drug, may be of therapeutic value in hyperserotonaemic autistic children, were the rationale for this clinical trial. Fenfluramine was administered to 4 treatment-resistant chronic schizophrenic in patients. They were studied for 14 weeks: 2 baseline weeks, 8 on fenfluramine (maximal dose 120 mg/day for 4 weeks) and 4 post-fenfluramine. Plasma levels of fenfluramine and nor-fenfluramine indicated good compliance. Platelet serotonin concentration decreased in all 4 subjects, weight loss was noted in 2. Clinical changes (assessed by rating psychiatric symptoms and ward behaviour) were observed in 3: moderate sustained improvement in 1, a short-lived activation followed by a slight improvement in another, and a brief amelioration with subsequent worsening in the third. The time and pattern of these changes suggest that they were due to fenfluramine. PMID- 2889762 TI - Epidemiology of nosocomial infections due to Acinetobacter calcoaceticus. PMID- 2889763 TI - Surveillance of colonization and late-onset septicaemia in neonates. AB - Twenty-seven newborns had an episode of late-onset sepsis (septicaemia or bacterial meningitis after 48 h of age) over an 18 month period. Preceding or simultaneous surface cultures were available from 26 babies. Colonization with the organism causing sepsis could only be documented in 10 cases. Colonization with aminoglycoside-resistant Gram negative organisms was common but there were only two cases of systemic sepsis with a resistant organism. Pseudomonas aeruginosa frequently colonized babies over the first 8 months of the survey, but subsequently virtually ceased to colonize babies, although it continued to be a common cause of late-onset sepsis. These findings do not support the utility of routine surveillance of organisms colonizing neonates in predicting bacteria causing late-onset sepsis. They also cast doubt on the value of eliminating colonizing organisms by expensive infection control measures. PMID- 2889764 TI - An outbreak of infection with a methicillin-resistant Staphylococcus aureus in a special care baby unit: value of topical mupirocin and of traditional methods of infection control. AB - This report deals with the problems associated with a high incidence rate of methicillin-resistant Staphylococcus aureus in low birth weight infants in a regional special care baby unit. Strict isolation facilities were not used and the outbreak was promptly brought under control by the use of intensive traditional methods of infection control and the use of topical mupirocin in a paraffin base. PMID- 2889765 TI - Control of a Serratia marcescens outbreak in a maternity hospital. AB - During the period between October 1984 and January 1985, an outbreak of Serratia marcescens took place in the Serlin Maternity Hospital in Tel-Aviv. Four major and six minor infections were noted in newborn and preterm infants. An additional group of 24 neonates were asymptomatic carriers of S. marcescens. Extensive control measures were undertaken, including closing the SCBU to further admissions and the opening of a new SCBU. Other measures included maintaining babies in cohort groups, strict handwashing, and use of gloves and gowns. There was also intensified encouragement of breast feeding and thorough cleansing and disinfection of the SCBU and nurseries. After 3 months, the outbreak was controlled. No identified source for the outbreak was detected. We feel that the extensive measures employed were responsible for controlling the outbreak within a relatively short time. PMID- 2889766 TI - Estimating the infection rate in mothers following caesarean section. AB - Some hospitals send comparatively few swabs to their laboratories for examination, consequently any measure of infection that depends on routinely analysed swabs is likely to underestimate the actual level of infection. In a survey of routine wound swabs from mothers following caesarean section, it was found that the average infection rate in 31 hospitals was 6%, with considerable variation between the hospitals. Further consideration of the data as described in this paper shows that the actual infection rate was about 14%, with much less variation between hospitals. PMID- 2889767 TI - Biotyping of Acinetobacter calcoaceticus using the API 2ONE system. AB - The API 2ONE system for the identification of non-fermentative Gram-negative bacilli enables the discrimination of a possible 209 different biotypes of Acinetobacter spp. and consequently has potential for use as an Acinetobacter spp. typing system. A total of 122 separate strains of Acinetobacter spp. isolated in Nottingham hospitals over a 4 year period from a wide variety of clinical specimens, divided into 31 different biotypes which were stable over a 1 year storage period. Two biotypes predominated, one of which was a multiply resistant strain of A. calcoaceticus variant anitratus. The API 2ONE system was found to be a rapid method for biotyping strains of Acinetobacter spp. and was helpful in monitoring cross-infection and spread of particular strains of Acinetobacter spp. in the hospital environment. PMID- 2889768 TI - Seasonal prevalence of nosocomial Aeromonas hydrophila infection related to aeromonas in hospital water. AB - A seasonal variation in nosocomial Aeromonas hydrophila infection was correlated with the number of aeromonas in the hospital water supply. The high summer prevalence of A. hydrophila infection coincided with periods when water counts from storage tanks were highest. The waterborne origin of these infections highlights the importance of maintaining clean water supplies, especially where storage tanks are used. Monitoring A. hydrophila in hospital water, particularly during the summer months, may prove helpful. PMID- 2889769 TI - Acquisition of endemic Pseudomonas aeruginosa on an intensive therapy unit. AB - During a 9-month period, patients, staff and environment were monitored in order to trace the source of endemic Pseudomonas aeruginosa on our intensive therapy unit (ITU). Of 81 patients studied, 14 (17%) acquired 15 different pyocin types while on the ITU. The most frequent site of colonization was the rectum (11 patients). Rectal strains subsequently appeared in urine (two patients), wound (one) and sputum (four) of six patients. Three episodes of cross-infection (wound (two), urine (one] occurred without development of rectal colonization. Strains isolated from the environment and staff were not implicated. While gastrointestinal carriage of P. aeruginosa may not be detected on admission to the ITU, excessive use of antibiotics may be responsible for apparent acquisition of the organism followed by endogenous transfer of the rectal strains to other sites of the body. PMID- 2889770 TI - A placebo-controlled trial of the effect of two preoperative baths or showers with chlorhexidine detergent on postoperative wound infection rates. AB - The effect of preoperative whole-body washing with chlorhexidine detergent on the incidence of postoperative wound infection was assessed in a placebo-controlled trial of 1989 patients. Patients bathed or showered with chlorhexidine, placebo, or conventional bar soap, on two occasions in the 24 h before operation. The overall infection rate for patients treated with chlorhexidine was 9%, against 12.8% in the bar soap and 11.7% in the placebo groups; in the 'clean' surgery group infections were 7.2% against 10.2% and 10%, respectively. The Staphylococcus aureus infection rate in the 'clean' group was 3% for chlorhexidine against 6% for bar soap. PMID- 2889771 TI - Contamination of the environment of spinal cord injured patients by organisms causing urinary-tract infection. AB - Various environmental sites closely associated with spinally-injured patients were examined for contamination by organisms concurrently causing urinary infection. Of 30 episodes studied, the same organism was recovered from bedding on 20 occasions, from nine of 20 bath towels and less frequently from face cloths, clothing, wheelchairs and bedside units. The results indicate that contact with the immediate environment of spinal patients with urinary infection may lead to contamination of hands, and confirm and expand the need for handwashing by patients and staff. PMID- 2889772 TI - Pseudomonas peritonitis in continuous ambulatory peritoneal dialysis: laboratory predictors of treatment failure. AB - Five episodes of pseudomonas peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD) which were not cured by intraperitoneal antibiotics were studied to assess causes for treatment failure. The activity of gentamicin and ceftazidime against these strains was decreased in the presence of sterile used dialysate compared with nutrient broth. Likewise, kinetic studies showed that in dialysate therapeutically used concentrations of antibiotics failed to kill the isolates over 24 h. All five pseudomonas strains were adherent to silicone rubber Tenckoff catheter segments. An in vitro model of CAPD peritonitis demonstrated that persistence of viable adherent bacteria, after exposure to therapeutic concentrations of gentamicin and ceftazidime, contributes to the failure of antibiotics to cure pseudomonas CAPD peritonitis. PMID- 2889773 TI - 'Methicillin-resistant' Staphylococcus aureus in a regional neonatology unit. AB - In December 1985 a neonate was transferred to a Yorkshire Regional Neonatology Unit (RNU) from a neighbouring hospital and was subsequently found to be colonized with a 'methicillin-resistant' strain of Staphylococcus aureus (MRSA). Spread of the MRSA was controlled by routine cross-infection methods. The RNU was not closed to new admissions, the economic cost of control measures was small and no neonatal death was attributable to MRSA infection. Eradication of the MRSA from the RNU was associated with a decline in frequency of coagulase-negative staphylococci (CNS) from blood cultures, but the overall frequency of positive blood cultures did not decline and there was a rise in frequency of isolation of Gram-negative bacterial species. The decline in frequency of CNS isolates from blood cultures may have resulted from a reduction in the level of cross colonization of neonates with antibiotic-resistant CNS strains and also increased usage of erythromycin and vancomycin. PMID- 2889774 TI - Colonization of patients with spinal cord injury with Pseudomonas aeruginosa and Klebsiella pneumoniae at different institutions. AB - Colonization of patients with Pseudomonas aeruginosa and Klebsiella pneumoniae was studied in patients with spinal cord injury at two institutions in Los Angeles County. The method of care of patients was similar at both institutions. A high prevalence of perineal colonization with P. aeruginosa and K. pneumoniae and similar serotypes of Pseudomonas were seen at both institutions. This colonization probably reflects the type of bladder management in patients with spinal cord injury. It would be of interest to examine other facilities to determine if colonization is influenced by techniques or local factors. PMID- 2889775 TI - Contamination of small-volume medication nebulizers and its association with oropharyngeal colonization. AB - The effect of the use of small-volume medication nebulizers on oropharyngeal colonization with potentially pathogenic Gram-negative bacilli was investigated in 95 patients with respiratory disease, of whom 54 used nebulizers and 41 were controls. Inhalation therapy had a significant effect on colonization, with a relative risk of more than four. Age over 60 years also showed a significant association with colonization. One-third of the nebulizers sampled were contaminated, 71% with Gram-negative bacilli. A direct route of contamination could be demonstrated in 28% of the patients. Medication nebulizers should be thoroughly cleaned after use and stored dry between patients. PMID- 2889776 TI - What makes human immunodeficiency virus (HIV) resistant to dry heat inactivation? PMID- 2889777 TI - Hospital outbreak of multi-resistant Acinetobacter anitratus: an airborne mode of spread? PMID- 2889778 TI - Multi-resistant Staphylococcus aureus. PMID- 2889779 TI - Effect of alpha 1-adrenoceptor blockade on blood pressure and iliac vascular resistance in normotensive and Goldblatt hypertensive dogs; influence of dietary salt and DOCA-salt. AB - Instrumented normotensive and two-kidney, one clip Goldblatt hypertensive dogs were placed on normal salt, high salt and DOCA-salt regimens and the effect on mean arterial blood pressure (MAP) and iliac vascular resistance (IVR) determined. High salt and DOCA-salt did not alter these variables in the Goldblatt hypertensive group. DOCA-salt increased MAP in the normotensives by 12 mmHg; however, IVR was not significantly increased by this treatment. In order to determine the degree of sympathetic tone in the iliac vascular bed, the change in IVR evoked by the alpha 1-adrenoceptor antagonists, urapidil and prazosin, was assessed. There were similar reductions in MAP and IVR after alpha 1-blockade in both groups of dogs, regardless of the salt regimen. However, urapidil caused a greater decrease in MAP in the normotensives than in the hypertensives. Captopril administration after alpha 1-blockade caused further reductions in MAP and IVR in the hypertensives, and in the MAP of the normotensive dogs on normal or high salt, indicating that the renin-angiotensin system maintained blood pressure in these groups. These results suggest that sympathetic tone is not increased by high salt- or DOCA-salt in normotensive or Goldblatt hypertensive dogs for the 8 11 day duration of these treatments. PMID- 2889780 TI - Immunosuppression by succinylacetone. II. Prevention of graft-vs-host disease. AB - Succinylacetone is a seven-carbon organic ketoacid that we have previously shown to inhibit tumor allograft rejection as well as the primary antibody response to sheep erythrocytes in rats. Because it appeared to be such a potent immunosuppressive agent in our initial studies, we evaluated succinylacetone for its ability to block graft-vs-host disease (GVHD) in adult F1 rats injected with parental strain spleen cells. Untreated ACE X Lewis F1 rats given Lewis strain spleen cells died of GVHD, with a mean survival of 24 days. By contrast, 62% of F1 rats in the group treated with succinylacetone survived, and the deaths that occurred in this group occurred significantly later. To confirm this observation and determine whether succinylacetone would interfere with bone marrow engraftment, lethally irradiated adult Wistar-Furth rats were reconstituted with syngeneic or totally allogeneic Fisher 344 lymphohemopoietic cells consisting of equal numbers of bone marrow and spleen cells. All animals given allogeneic cells without additional immunosuppressive treatment developed severe GVHD and died by day 42. By contrast 92% of the allogeneic cell recipients that had been treated with succinylacetone were long term survivors. Cytotoxicity typing of peripheral lymphocytes demonstrated greater than 90% donor-type lymphocytes persisting in the succinylacetone-treated recipients as long as 255 days post-transplantation. No chronic or late developing acute GVHD was observed even though the animals received succinylacetone as the sole immunosuppressant for only 28 days after transplantation. Furthermore, hemopoietic reconstitution in recipients of syngeneic cells was essentially identical between the control group and the group treated with succinylacetone. In addition, no gross or histologic evidence for renal, hepatic, cardiovascular, endocrine, or neurologic toxicity was observed in the long term transplant survivors treated with succinylacetone. These data indicate that succinylacetone treatment is effective in preventing lethal GVHD in this allogeneic bone marrow transplantation system while permitting normal hemopoietic reconstitution in the absence of significant chronic toxicity to other major organ systems. PMID- 2889781 TI - Improved procedure for the isolation of functionally active lymphoid cells from the murine intestine. AB - An isolation procedure for functionally active lamina propria lymphoid cells (LPL) from the murine intestine is described. The procedure involved EDTA dithiothreitol incubation of intestinal tissue to remove epithelial and intraepithelial cells, followed by collagenase digestion of the basement membrane to liberate part of the LPL. The LPL were suspended by squeezing the remaining tissue strips through a nylon gauze filter. Functional activity was tested by enumeration of the immunoglobulin-secreting cells in the cell suspensions obtained by an isotype-specific protein A plaque-forming cell assay. On average 1 2 X 10(8) LPL were isolated from the intestine of C3H/He mice. 11% of these cells actively secreted Ig. From these Ig-secreting cells 99% produced IgA. The isolation procedure described in this paper permitted a higher recovery of viable cells than has previously been obtained with other methods. PMID- 2889783 TI - Ratio of Langerhans cells to Thy-1+ dendritic epidermal cells in murine epidermis influences the intensity of contact hypersensitivity. AB - We have initiated a series of studies in vivo to investigate the physiologic role of Langerhans cells and Thy-1+ dendritic epidermal cells in the development and regulation of contact hypersensitivity. The density of I-A+ Langerhans cells and Thy-1+ dendritic epidermal cells in ammonium thiocyanate-separated epidermal sheets was determined in ten strains of inbred mice using immunofluorescence microscopy with monoclonal anti-I-A and anti-Thy-1 antibodies. Mice of different inbred strains were sensitized by painting the left ear with varying doses of either oxazolone or trinitrochlorobenzene. From five to 20 days after sensitization, groups of mice were challenged with the relevant antigen and the intensity of contact hypersensitivity, as measured by ear swelling, was determined. We then determined whether the intensity and/or duration of contact hypersensitivity in different strains of mice was influenced by the density of Thy-1+ dendritic epidermal cells or the ratio of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells. We found that there was marked variability in the density of Thy-1+ dendritic epidermal cells and I-A+ Langerhans cells in the ten strains of mice studied. The ratio of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells ranged from 0.5 in C57BL/10J mice to greater than 22 in A/J and BALB/cByJ mice. When small amounts of contact sensitizers were used to induce contact hypersensitivity (e.g., 20 micrograms of oxazolone or trinitrochlorobenzene), there was consistent strain variability in the intensity of ear swelling. There was a significant correlation between the ratio of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells and the intensity of contact hypersensitivity (Pearson's correlation coefficient 0.85, p = 0.002). Strains with the highest ratios of I-A+ Langerhans cells to Thy-1+ dendritic epidermal cells had the most ear swelling. There were no consistent differences in the duration of contact hypersensitivity observed among the ten different strains. Our results indicate that Thy-1+ dendritic epidermal cells may play a physiologic role in down-regulating contact hypersensitivity in vivo. PMID- 2889784 TI - Nurses' knowledge of pain issues: a survey. PMID- 2889782 TI - Rapid induction of Thy-1 antigenic markers on keratinocytes and epidermal immune cells in the skin of mice following topical treatment with common preservatives used in topical medications and in foods. AB - Earlier experiments from our laboratory revealed that the medication most commonly used for depigmenting patients with vitiligo, monobenzyl ether of hydroquinone (MBEH), when applied to the skin of DBA/2 mice caused an increase in the population density (cells/mm2) of identifiable Ia+ and ATPase+ Langerhans cells. Further, this increase in Langerhans cell density could be correlated with an increase of contact hypersensitivity (CHS) reactivity to dinitrofluorobenzene (DNFB). The current experiments demonstrated that other compounds chemically similar to MBEH, such as butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA), which are used as preservatives/antioxidants in many topical medications, cosmetics, food, and rubber products, can in five days significantly increase the population density of Thy-1+ dendritic epidermal cells. These compounds had no effects on Ia+ cells. This observation suggests that the Thy-1+ DEC cells may be more mobile and/or their surface markers may be readily expressed and are not a slowly mobile (trafficking) population of cells as suggested by the results of previous work. In addition, these parasubstituted phenolic compounds behaved like pertussis toxin and induced Thy-1 and Ia expression on keratinocytes. These changes in Thy-1 immune markers were not accompanied by functional alterations in the immune response to contact allergens as measured by the ear swelling technique. PMID- 2889785 TI - [A case of smoldering adult T-cell leukemia with generalized cryptococcosis]. PMID- 2889786 TI - Synthesis of a thiophosphate analog of dioctanoylphosphatidylcholine: a phospholipase C substrate. AB - Dioctanoylthiophosphatidylcholine, a racemic thiophosphate analog of L-alpha dioctanoylphosphatidylcholine, has been synthesized and isolated by flash chromatography. In contrast with the didecanoylthiophosphatidylcholine synthesized previously, the analog is easily dispersed on sonication in aqueous media and is rapidly hydrolyzed to produce a free thiol group in the presence of the extracellular phospholipase C from either Bacillus cereus or Clostridium perfringens. When 5,5'-dithiobis (2-nitro-benzoic acid) was included as a thiol reactive chromogenic agent, the resultant measurement of product release, as an increase in absorbance at 412 nm, showed a linear relationship with added enzyme. PMID- 2889787 TI - Influence of streptozotocin-induced diabetes on the concentration of immunoreactive somatostatin in the retina and peripheral blood of the rat: effect of insulin treatment. AB - Changes in somatostatin-like immunoreactivity (SLI) were examined in the retina and peripheral blood of diabetic rats treated with streptozotocin (STZ) and insulin. There was no change in retinal SLI content at 4 and 11 days after administration of STZ but, thereafter, SLI increased progressively in the diabetic animals by 220% at 18 days and 300% at 27 days. Plasma SLI levels increased by 500% at 11 days and maintained similar levels thereafter. Diabetic animals treated with insulin (3-5 i.u. daily) for 27 days showed a significant (P less than 0.01) decrease of retinal and plasma SLI levels compared with untreated diabetic animals. It is concluded that there is a significant increase of retinal and plasma SLI levels in diabetic rats which tends to normalize after several days of insulin treatment. PMID- 2889788 TI - In-vivo evaluation of dopamine receptor-mediated inhibition of gonadotrophin secretion from the pituitary gland of the goldfish, Carassius auratus. AB - Dopamine acts directly on the pituitary to modulate gonadotrophin (GtH) secretion in goldfish (Carassius auratus). In the light of this important role for dopamine in the regulation of goldfish reproduction, this investigation was designed to evaluate the receptor specificity of this dopamine inhibition and to describe the use of domperidone, a specific dopamine D2-receptor antagonist, in the manipulation of pituitary function in goldfish. To investigate the specificity of dopamine inhibition of GtH secretion, selected dopamine receptor antagonists were injected i.p. to block dopamine receptors thereby increasing GtH secretion as reflected by increased serum concentrations of GtH. Serum GtH levels were significantly increased by the active stereoisomer (-)-sulpiride in a dose related fashion; (+)-sulpiride had no effect. Comparison of dopamine antagonists at low doses indicated that only domperidone and pimozide caused significant increases in serum concentrations of GtH. Dopamine antagonists potentiated the action of a gonadotrophin-releasing hormone analogue (GnRH-A) with an order of potency of domperidone = pimozide greater than metoclopramide = fluphenazine. [3H]Domperidone, injected i.p. with unlabelled domperidone, entered the blood and achieved maximum concentrations 12 h after injection, but did not accumulate in the brain in appreciable amounts. Gonadal 3H radioactivity was usually equal to or in excess of blood radioactivity, while [3H]domperidone was highly concentrated in the pituitary in a time-dependent fashion, with maximal accumulation occurring 24 h after injection. The time-course of pituitary accumulation of [3H]domperidone correlated well with the temporal increase in serum GtH levels in response to i.p. injected domperidone or domperidone plus an analogue of LHRH. Domperidone increased serum concentrations of GtH in a dose related fashion; an analogue of salmon GnRH (sGnRH-A) increased the sensitivity and magnitude of the serum GtH response to domperidone. Serum concentrations of GtH were increased by sGnRH-A in a dose-related fashion; a low dose of domperidone substantially increased the sensitivity of the serum GtH response to sGnRH-A. These results indicate that dopamine inhibits GtH secretion from the goldfish pituitary by acting through a specific mechanism mediated by a dopamine D2 receptor. Domperidone increased serum concentrations of GtH, potentiated the action of gonadotrophin-releasing hormones and did not pass into the brain after i.p. injection into goldfish. The data also suggest that dopamine and GnRH, although acting through different receptors, influence the effect of each other on GtH release. PMID- 2889789 TI - Endocrine control of plasma concentrations of calcium-binding protein in the pig. AB - The aetiology of the rise in plasma calbindin-D9K (vitamin D-induced calcium binding protein; CaBP), following insulin-induced hypoglycaemia, was studied in the pig. ACTH led to a rise in plasma concentrations of both CaBP and cortisol. Metyrapone, which blocks cortisol synthesis, abolished the increases in plasma concentrations of CaBP and cortisol normally observed in response to insulin induced hypoglycaemia. However, there was no significant rise in plasma concentrations of CaBP in response to pharmacological or physiological doses of cortisol. Injection of clonidine, an alpha 2-adrenergic agonist, led to a rise in plasma concentrations of CaBP, whereas phenylephrine, an alpha 1-adrenergic agonist, tended to exert an inhibitory effect. Also, administration of phentolamine (an alpha-adrenergic blocker) before injection of insulin abolished the usual increase in plasma concentrations of CaBP, whereas propranolol (a beta adrenergic blocker) enhanced the normal increase in plasma concentrations of CaBP in response to insulin-induced hypoglycaemia. Isoproterenol, a beta-adrenergic agonist, was without effect on plasma CaBP. Neither GH nor glucagon appear to be involved in the rise in plasma CaBP following insulin-induced hypoglycaemia. Although atropine abolished the effect of acute hypoglycaemia on plasma CaBP, carbamylcholine was without effect on plasma CaBP concentration. It is concluded that the increases in plasma CaBP induced by either ACTH or alpha 2-adrenergic stimulation may be interrelated since the administration of ACTH can lead to raised plasma concentrations of catecholamines. PMID- 2889790 TI - Studies of the parathyroid hormone gene in normal subjects, and in subjects with primary hyperparathyroidism and familial benign hypercalcaemia. AB - Familial benign hypercalcaemia (FBH) closely resembles primary hyperparathyroidism (PHPT) both clinically and biochemically. Using a cDNA probe for the parathyroid hormone (PTH) gene we have studied restriction fragment length polymorphisms in normal British subjects and have shown them to be similar to those found in previous studies in a German population. The pattern of inheritance of these restriction fragment length polymorphisms in a family with FBH shows that the PTH gene is not involved in the pathogenesis of the condition. Limited studies in PHPT indicate that it is unlikely that a major structural defect or rearrangement is responsible for the sporadic form of the disease. PMID- 2889791 TI - Inter-strain homology of pilin gene sequences in Neisseria meningitidis isolates that express markedly different antigenic pilus types. AB - Neisseria meningitidis isolates examined in this study elaborated one of two pilus types that were antigenically markedly different. Each pilus type reacted either with SM1, a monoclonal antibody that recognizes an epitope common to all gonococcal pili, or with a polyclonal antiserum raised against meningococcal pili that did not react with SM1, but not both. Total genomic DNA from all N. meningitidis isolates analysed, irrespective of pilus type, contained at least one region with extensive homology to a gonococcal pilE probe. Different N. meningitidis strains possessed one of several configurations of genomic pilE homologous segments. Chromosomal rearrangement of pilE-homologous sequences was associated with P+ to P- pilus phase transition in the strains examined. The arrangement of pilE-homologous segments in total genomic DNA from N. meningitidis isolated from the blood and cerebro-spinal fluid of the same patient was apparently identical. PMID- 2889792 TI - Chromosomal DNA probes for the identification of Bacteroides species. AB - We compared 22 Bacteroides species by DNA-DNA homology studies using the S1 endonuclease method. None of the currently defined species shared more than 30% DNA homology with any other species examined with the exception of B. buccae and B. capillus (which along with B. pentosaceus are now considered a single species), which shared 86% of their DNA sequences. Two clusters showed weak genetic relationships, with DNA homology greater than 10%. The first cluster included B. coporis, B. disiens, B. bivius, B. intermedius and B. melaninogenicus. The second cluster included B. fragilis, B. eggerthii, B. ovatus, B. thetaiotaomicron and B. uniformis. Five of the oral species, B. asaccharolyticus, B. gingivalis, B. loescheii, B. intermedius and B. melanogenicus, were chosen for study as whole chromosomal probes in dot blot assays. These were tested against 243 clinical strains biochemically identified as Bacteroides species. The DNA probes correctly identified 94% of the clinical strains. DNA probe and biochemical identification was 100% for two of the five species. In contrast, only 86% of the strains biochemically identified as B. intermedius were identified by the DNA probe. The DNA probes gave a species identification to seven strains which could not be biochemically identified. PMID- 2889793 TI - glnA mutations conferring resistance to methylammonium in Escherichia coli K12. AB - Cells of Escherichia coli K12 were sensitive to 100 mM-methylammonium when cultured under nitrogen limitation, and resistant when grown with an excess of either NH4Cl or glutamine. Glutamine synthetase activity was required for expression of the methylammonium-sensitive phenotype. Mutants were isolated which were resistant to 100 mM-methylammonium, even when grown under nitrogen limitation. P1 bacteriophage transduction and F' complementation analysis revealed that the resistance-conferring mutations mapped either inside the glnA structural gene and/or elsewhere in the E. coli chromosome. Glutamine synthetase was purified from the wild-type and from some of the mutant strains. Strains carrying glnA-linked mutations that were solely responsible for the methylammonium-resistant phenotype yielded an altered enzyme, which was less active biosynthetically with either ammonium or methylammonium as substrate. Sensitivity to methylammonium appeared to be due to synthesis of gamma glutamylmethylamide by glutamine synthetase, which was synthesized poorly, if at all, by mutants carrying an altered glutamine synthetase enzyme. PMID- 2889794 TI - Linkage of the scrapie-associated fibril protein (PrP) gene and Sinc using congenic mice and restriction fragment length polymorphism analysis. AB - Sinc, with two alleles p7 and s7, is the major gene determining the incubation period of all strains of scrapie in mice. The major protein (PrP) of scrapie associated fibrils is encoded by a cellular gene and we have used a cDNA copy of the hamster PrP mRNA to carry out restriction fragment length polymorphism (RFLP) analysis of different inbred mouse strains including VM(Sincp7) and VM(Sincs7) congenic mice. In VM(Sincp7) mice, a 5.5 kb XbaI fragment hybridized to the PrP cDNA sequence whereas VM(Sincs7) congenic mice had a 3.8 kb XbaI fragment. The VM X VM(Sincs7) congenic F1 mice had both the 5.5 kb and the 3.8 kb fragments. The Sincs7 donor mouse strain, C57BL, had the 3.8 kb fragment suggesting that the Sinc gene and the gene coding for PrP are linked, and could even be the same gene. Other Sincp7 inbred mice (IM and MB) had the 5.5 kb fragment but so too did some Sincs7 strains (RIII and VL), implying that the XbaI site polymorphism is not functionally involved in the difference between the two Sinc alleles. We have mapped the polymorphic XbaI site to the 3' flanking region of the PrP gene. TaqI and HhaI were also found to show polymorphisms in the inbred mouse strains studied. The apparent RFLP with HhaI may be a result of differences in methylation rather than in sequence. PMID- 2889795 TI - Central action of ipsapirone, a new anxiolytic drug, on serotoninergic, noradrenergic and dopaminergic functions. AB - Ipsapirone (TVX Q 7821, 2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-1,2 benzisothiazol-3- (2H)one-1, 1-dioxidehydrochloride), a new anxiolytic drug in respect of the evaluation of its effect on central 5-hydroxytryptamine (5-HT), noradrenaline and dopamine functions was studied. It was found that ipsapirone inhibits induced by 8-OH-DPAT and 5-methoxydimethyltryptamine (agonists of 5-HT1A receptors) behavioural effects (flat body posture and forepaw treading) in normal and reserpinized rats. Ipsapirone partly inhibited in rats but not in mice the 8 OH-DPAT-induced hypothermia. Ipsapirone, administered at high doses, decreased the body temperature in rats and mice, inhibited the 5-hydroxytryptophan-induced head twitches in mice and the tryptamine-induced convulsions and tremor in rats. In the hind limb flexor reflex preparation of the spinal rat only high doses of the drug inhibited stimulation induced by quipazine, m-chlorphenylpiperazine, 8 OH-DPAT and St 587 (an agonist of alpha 1-adrenoceptors). Ipsapirone did not block the fenfluramine- and m-chlorphenylpiperazine-induced hyperthermia in rats at an ambient temperature of 28 degrees C. The drug did not affect clonidine induced sedation and inconsiderably attenuated clonidine-induced hypothermia in mice. It attenuated the d-amphetamine-induced locomotor hyperactivity in mice and rats but, given alone, decreased the locomotor activity. The obtained results indicate that ipsapirone exhibits 5-HT1A antagonistic effect, and only at high doses it can also produce an inhibitory effect on 5-HT2 and the alpha 1 adrenergic function. PMID- 2889796 TI - In vivo microdialysis studies on the effects of decortication and excitotoxic lesions on kainic acid-induced calcium fluxes, and endogenous amino acid release, in the rat striatum. AB - The in vivo effects of kainate (1 mM) on fluxes of 45Ca2+, and endogenous amino acids, were examined in the rat striatum using the brain microdialysis technique. Kainate evoked a rapid decrease in dialysate 45Ca2+, and an increase in the concentration of amino acids in dialysates in Ca2+-free dialysates. Taurine was elevated six- to 10-fold, glutamate two- to threefold, and aspartate 1.5- to twofold. There was also a delayed increase in phosphoethanolamine, whereas nonneuroactive amino acids were increased only slightly. The kainic acid-evoked reduction in dialysate 45Ca2+ activity was attenuated in striata lesioned previously with kainate, suggesting the involvement of intrinsic striatal neurons in this response. The increase in taurine concentration induced by kainate was slightly smaller under these conditions. Decortication did not affect the kainate evoked alterations in either dialysate 45Ca2+ or amino acids. These data suggest that kainate does not release acidic amino acids from their transmitter pools located in corticostriatal terminals. PMID- 2889797 TI - Alpha 2-adrenergic regulation of arylalkylamine N-acetyltransferase in organ cultured chick pineal gland: characterization with agonists and modulation of experimentally stimulated enzyme activity. AB - In the chicken pineal gland, norepinephrine, released at sympathetic nerve endings, plays a role in synchronizing the circadian rhythm of melatonin synthesis. This effect appears to be exerted via an adrenergic inhibition of arylalkylamine N-acetyltransferase, the melatonin rhythm-generating enzyme. The present study indicates that the nighttime peak of N-acetyltransferase activity developed by organ-cultured chick pineal glands is inhibited by adrenergic agonists with a potency order characterizing alpha 2-adrenergic receptors: UK 14,304 greater than clonidine greater than alpha-methylnorepinephrine = epinephrine greater than cirazoline greater than phenylephrine greater than isoproterenol. The mechanism of this alpha 2-adrenergic response was further analyzed in organ cultures, by studying the ability of clonidine to block the cyclic AMP-dependent and the depolarization-dependent stimulations of N acetyltransferase activity. Clonidine prevented the rise in N-acetyltransferase activity evoked by the adenylate cyclase activators forskolin and cholera toxin or by the phosphodiesterase inhibitor Ro 20,1724. The stimulatory effect of dibutyryl cyclic AMP was also blocked by clonidine. Activation of pineal alpha 2 adrenergic receptors effectively prevented the stimulation of N-acetyltransferase by depolarizing concentrations of KCl. The possibility that the alpha 2 adrenergic effect might be exerted at a step distal to cyclic AMP production is discussed. PMID- 2889798 TI - [3H]norepinephrine release from hippocampal slices is an in vitro biochemical tool for investigating the pharmacological properties of excitatory amino acid receptors. AB - [3H]Norepinephrine ([3H]NE) efflux from preloaded rat hippocampal slices was increased in a dose-dependent manner by excitatory amino acids, with the following order of potencies: N-methyl-D-aspartate (NMDA) greater than kainic acid (KA) greater than L-glutamate greater than or equal to D,L-homocysteate greater than L-aspartate greater than quinolinic acid greater than quisqualic acid. The effect of the excitatory amino acids was blocked by physiological concentrations of Mg2+, with the exception of KA. D,L-2-Amino-7 phosphonoheptanoic acid dose-dependently inhibited the NMDA effect (ID50 = 69 microM), whereas at 1 mM it was ineffective versus KA. The release of [3H]-NE induced by quinolinic acid was blocked by 0.1 mM D,L-2-amino-7 phosphonohepatanoic acid. gamma-D-Glutamylglycine dose-dependently inhibited the KA effect with an ID50 of 1.15 mM. Tetrodotoxin (2 microM) reduced by 40 and 20% the NMDA and KA effects, respectively. The data indicate that [3H]NE release from hippocampal slices can be used as a biochemical marker for pharmacological investigations of excitatory amino acid receptors and their putative agonists and antagonists. PMID- 2889799 TI - Formation and utilization of the active sulfate donor [35S]3'-phosphoadenosine 5' phosphosulfate in brain slices: effects of depolarizing agents. AB - The accumulation and utilization of [35S]3'-phosphoadenosine 5'-phosphosulfate (PAPS) were studied in slices from rat cerebral cortex incubated in the presence of inorganic [35S]sulfate. [35S]PAPS levels were directly evaluated after either isolation by ion-exchange chromatography or quantitative enzymatic transfer of its active [35S]sulfate group to an acceptor phenol under the action of added phenolsulfotransferase activity. [35S]PAPS formation was also indirectly followed by incubating slices in the presence of beta-naphthol and measuring the levels of [35S]beta-naphthyl sulfate ([35S]beta-NS). Whereas [35S]PAPS levels rapidly reached a plateau, [35S]beta-NS formation proceeded linearly with time for at least 1 h, an observation indicating that the nucleotide was continuously synthesized and utilized for endogenous sulfation reactions. [35S]PAPS formation in slices was completely and rather potently blocked by 2,6-dichloro-4 nitrophenol (IC50 = 10 microM), an inhibitor of the PAPS-synthesizing enzyme system in a cytosolic preparation. [35S]PAPS accumulation and [35S]beta-NS formation were strongly reduced by depolarizing agents such as potassium or veratridine. At millimolar concentrations, various excitatory amino acids (glutamate, aspartate, cysteate, quisqualate, and homocysteate) also elicited similar effects, whereas kainate and N-methyl-D-aspartate were inactive. This suggests that PAPS synthesis is turned off when cerebral cells are strongly depolarized. PMID- 2889800 TI - Stimulation of [3H]dopamine release by nicotine in rat nucleus accumbens. AB - The mesolimbic system of the brain has been shown to be involved in the reward properties of a number of agents. It is possible that release of monoamines by nicotine in this brain area could be related to the pleasurable aspects related to cigarette smoking. In this investigation, the effect of nicotine on the release of [3H]dopamine in the nucleus accumbens of the rat was studied. It was shown that nicotine produced a concentration-dependent increase in [3H]dopamine release at concentrations of 0.1 microM and above. The increase in release was found to be almost completely calcium dependent. The nicotine-induced release was only partially blocked by the nicotinic antagonists hexamethonium and d tubocurarine. A number of cholinergic agonists, as well as other compounds, were tested for their capacity to mimic the effect of nicotine. At equimolar concentrations there was, at most, only 50% of the activity of nicotine. The results of this study demonstrate that nicotine stimulates the release of dopamine in the nucleus accumbens at concentrations similar to those in the blood of cigarette smokers. This suggests that the release of monoamines in specific nuclei of the mesolimbic system may be an important determinant of the desire to smoke cigarettes. PMID- 2889801 TI - Utilization of plasma fatty acid in rat brain: distribution of [14C]palmitate between oxidative and synthetic pathways. AB - Radioactivity within individual brain compartments was determined from 5 min to 44 h after intravenous injection of [14C]palmitate into awake Fischer-344 rats, aged 21 days or 3 months. Total radioactivity peaked broadly between 15 min and 1 h after injection, declined rapidly between 1 and 2 h, and then more slowly. In 3 month-old rats, the lipid and protein brain fractions were maximally labeled within 15 min after [14C]palmitate injection, then retained approximately constant label for up to 2 days. Radioactivity in the aqueous brain fraction comprised mainly radioactive glutamate and glutamine, and peaked at 45 min, when it comprised 48% of total brain radioactivity, then decreased to 27% of the total at 4 h, 15% at 20 h, and 10% at 44 h. Percent distribution of radioactivity within the different brain compartments, 4 h after intravenous injection of [14C]palmitate, was similar in 21-day-old and 3-month-old rats, despite higher net brain uptake in the younger animals. The results indicate that about 50% of plasma [14C]palmitate that enters the brain of adult rats is incorporated rapidly into stable protein and lipid compartments. The remaining [14C]palmitate enters the aqueous fraction after beta-oxidation, and is slowly lost. At 4 h after injection, 73% of brain radioactivity is within the stable brain compartments; this fraction increases to 86% by 20 h. PMID- 2889802 TI - Immunohistochemistry and biosynthesis of N-acetylaspartylglutamate in spinal sensory ganglia. AB - N-Acetylaspartylglutamate (NAAG) is a nervous system-specific dipeptide which has been implicated in chemical neurotransmission. Antisera were prepared against NAAG in order to study its cellular distribution. When these antisera were applied to tissue sections of rat spinal sensory ganglia, NAAG-like immunoreactivity was detected within a subpopulation of relatively large neuronal cell bodies in cervical, lumbar, and thoracic ganglia. In order to confirm the presence of NAAG within these neurons, the dipeptide was extracted and purified from spinal ganglia using high-performance liquid chromatography and its composition confirmed by amino acid analysis. Further, the biosynthesis of NAAG was studied in vitro by following the incorporation of either [3H]glutamine or [3H]glutamate into the glutamate residue of the purified dipeptide. [3H]Aspartate was not incorporated efficiently into NAAG under these conditions, suggesting a precursor role for the large N-acetylaspartate pool. The incorporation of radiolabeled amino acids into newly synthesized NAAG by spinal sensory ganglia was not inhibited by incubation of the cells with anisomycin or cycloheximide at concentrations which significantly inhibited protein synthesis. These data suggest that NAAG is present in a subpopulation of primary afferent spinal neurons and that its biosynthesis is mediated by a dipeptide synthetase. PMID- 2889803 TI - Benzodiazepine receptor binding of triazolobenzodiazepines in vivo: increased receptor number with low-dose alprazolam. AB - Triazolobenzodiazepines are in clinical use as hypnotics and anxiolytics. We analyzed in vivo receptor binding and brain concentrations of alprazolam, triazolam, and estazolam. Drug concentrations measured in the cerebral cortex 1 h after administration were directly proportional to dose for all three compounds. In vivo receptor binding, as defined by the specific uptake of [3H]Ro15-1788, decreased with increasing doses of estazolam and triazolam, a finding indicating dose-related increases in receptor occupancy due to these compounds. Triazolam was substantially more potent, with an IC50 value of 16 ng/g, compared with 117 ng/g for estazolam. At higher doses of alprazolam (greater than 0.2 mg/kg), receptor binding by [3H]Ro15-1788, likewise decreased with increasing dose of the former drug. However, at lower doses of alprazolam (0.02-0.05 mg/kg), which resulted in cortex concentrations of 2-7 ng/g, receptor binding was increased above control values in cortex, hypothalamus, and hippocampus but not in several other brain regions. Binding returned to control values at doses of greater than or equal to 0.01 mg/kg. Similar results were obtained in time course studies. At 8 and 10 h after a dose of 1 mg/kg i.p., corresponding to cortex concentrations of 2.7-7 ng/g, receptor binding was increased compared with controls. Similarly, at 1, 2, and 3 h after a single dose of 0.05 mg/kg, corresponding to cortex concentrations of 3.7-5.8 ng/g, receptor binding was also increased. The apparent affinity of benzodiazepine receptors for clonazepam in mice receiving alprazolam (0.05 mg/kg) was unchanged from that in untreated control mice, an observation suggesting that low doses of alprazolam increased receptor number.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889804 TI - Neonatal and adult 6-hydroxydopamine-induced lesions differentially alter tachykinin and enkephalin gene expression. AB - The present investigation examined the effects of neonatal and adult 6 hydroxydopamine (6-OHDA)-induced lesions of dopaminergic neurons on opioid and tachykinin peptides and their gene expression in the rat basal ganglia. This work was undertaken to determine if changes in these neuropeptide systems were contributing to the differing behavioral responses observed between neonatally and adult-lesioned rats after dopamine agonist administration. [Met5]Enkephalin (ME) content was increased in striatal tissue from both 6-OHDA-lesioned groups when compared with unlesioned controls. Dynorphin-A (1-8) content was not altered by the 6-OHDA lesions. The tachykinin peptides substance P and neurokinin A were significantly decreased in level in the striatum and substantia nigra of neonatally lesioned rats, but not in the adult-lesioned rats, when compared with unlesioned controls. Proenkephalin mRNA abundance (quantified by an RNA-cDNA hybridization technique) and precursor level (as reflected by cryptic ME content) were increased in the striatum of both neonatally and adult-lesioned rats. The abundance of preprotachykinin mRNA coding for the tachykinin peptides was markedly decreased in the neonatally lesioned rats, whereas only a small reduction was observed in the adult-lesioned rats. These results suggest that destruction of dopamine-containing terminals with 6-OHDA elevates the level of ME by accelerating transcriptional and/or translational processes; conversely, the reduced content of tachykinins in neonatally lesioned rats may be due to a reduction in such processes. Thus, preproenkephalin-A and preprotachykinin gene expression are differentially regulated after lesioning of catecholamine containing neurons, an observation suggesting a close functional relationship among these neurotransmitter systems. Furthermore, of the peptides studied, only levels of the tachykinin peptides were differentially altered in the striatum and substantia nigra of the neonatally lesioned rats compared with adult-lesioned rats; therefore, these peptides may be associated with the distinctive behavioral differences between neonatally and adult 6-OHDA-lesioned rats given dopamine agonists. PMID- 2889805 TI - Factors affecting the outcome in subdural empyema. AB - The case reports of 102 patients with subdural empyema, diagnosed in the years 1935-83, were reviewed to determine the factors affecting the outcome. Statistical analysis (likelihood ratio tests with chi square approximation and logistic regression) showed that year of diagnosis (p less than 0.01) and level of consciousness at the moment of diagnosis (p less than 0.01) had a significant bearing on the chance to survive and that these same two factors (each factor p less than 0.01) and extent of subdural pus accumulation at the moment of diagnosis (p less than 0.05) had a significant bearing on the chance of survival without severe disability. Among others the duration of the disease up to the moment of diagnosis and the mode of the first surgical procedure had no significant bearing on the outcome. These results together with those in the literature are discussed and it is concluded that diagnosis and treatment before the patient lapses into stupor or coma, increases the chance of survival and that with adequate management a mortality rate of 10% or lower is to be expected. PMID- 2889806 TI - Fixed-dose combination medications for the treatment of hypertension: a critical review. AB - Aside from the retrospective analysis of Clark and Troop (1), no large-scale controlled study has been designed specifically to assess the advantages and disadvantages of fixed-dose antihypertensive combinations. The use of fixed-dose antihypertensive combinations is no longer the anathema of the academician. The principal advantages of fixed-ratio combinations are simplicity of use, potentiation of blood-pressure-lowering efficacy, and potential counterbalancing of certain side effects. An additional advantage might be improvement in broad based cost effectiveness, that is, a potential reduction in the need for frequent laboratory surveillance and in the frequency of office visits. The principal disadvantage is the relative inflexibility of dosage adjustment. Antihypertensive therapy should be initiated with a single drug preparation, with subsequent substitution of a combination product when appropriate. Tables 4 and 5 summarize, respectively, some of the important factors to consider and the theoretical requirements when contemplating the use of fixed-dose antihypertensive combinations. Diuretic/beta-blocker combinations are particularly attractive because of the enormous long-term experience with each component, their proven efficacy and additional salutary effects, their generally acceptable and sometimes offsetting side effects, and their potential for once-a-day dosing. It seems likely that CEI/diuretic and perhaps calcium-channel blocker/diuretic combinations also have great merit. PMID- 2889807 TI - Relations between vascular structure and blood pressure. PMID- 2889808 TI - Structural and functional modifications of peripheral large arteries in hypertensive patients. PMID- 2889809 TI - Fetal frontal cortex transplanted to injured motor/sensory cortex of adult rats. II. VIP-, somatostatin-, and NPY-immunoreactive neurons. AB - Fetal frontal cortex transplants that survived 2-9 months in cavities in adult rat motor/sensory cortex were processed for vasoactive intestinal polypeptide (VIP), somatostatin 14 (SS), and neuropeptide Y (NPY) immunocytochemistry, and NADPH-diaphorase (NADPH-d) histochemistry. All transplants had surviving VIP, SS, NPY, and NADPH-d neuronal perikarya and fibers with normal adult morphology. The number of peptidergic neurons within transplants, however, often appeared to be less than that in equivalent areas of host cortex. Most transplanted SS and VIP neuronal perikarya did not migrate to form the laminae characteristic of normal cortex. A few transplants had SS and VIP cells arranged in laminae in which the VIP processes were parallel to one another and perpendicular to one transplant surface, approximating normal host neocortex. VIP, NPY, and SS fibers crossed between host brains and transplants, suggesting that peptide host-transplant interactions are possible. All adult host cortical and most transplanted NPY neurons colocalized with NADPH-d. The failure of some transplanted NPY neurons to express NADPH-d suggests these transplanted cells may be functionally impaired, but that they can survive without the NADPH-d enzyme. PMID- 2889810 TI - Calcium antagonists: a review of the recent comparative trials. AB - A review of published studies was undertaken to assess the efficacy and patient tolerability of calcium antagonists compared with established antihypertensive therapy, i.e. beta-blockers and diuretics. Randomized controlled trials undertaken in Caucasian patients with mild to moderate hypertension were evaluated. Only 12 trials fulfilled the criteria for inclusion in the review and they differed considerably with regard to design, method of analysis, and drug and dose regimen used; a formal pooled analysis of the data was not feasible. Few trials demonstrated significant differences in blood pressure control between treatments. Side effects were rarely seen, or were not assessed, and the number of patients studied was relatively small. Two large unpublished trials have recently evaluated the slow-release twice-daily formulation of 20 mg nifedipine, 50 mg atenolol and the fixed combination of 50 mg atenolol + 20 mg nifedipine, using a randomized double-blind crossover design. Mean blood pressure with atenolol was consistently lower than with nifedipine although this achieved statistical significance in only one study (P less than 0.01). Fixed combination therapy gave a greater antihypertensive effect than either atenolol or nifedipine administered alone (P less than 0.05 to P less than 0.001). Side effects were most common with nifedipine treatment, less common with combination therapy and occurred least commonly with atenolol alone (P less than 0.001). In one study involving 44 patients (aged 20-70 years), side effects attributable to peripheral vasodilation secondary to nifedipine therapy, e.g. flushing and sweats, were significantly greater (P less than 0.05) with nifedipine (n = 11) than with atenolol (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2889811 TI - Angiotensin converting enzyme inhibitors in the clinic: quality of life. AB - In mild to moderate hypertension the benefit:risk ratio of treatment cannot be predicted for an individual patient. Antihypertensive drug therapy can therefore only be justified if the patient's quality of life remains unimpaired. Angiotensin converting enzyme (ACE) inhibitors are considered to improve the 'quality of life'. However, only two trials have assessed the influence of antihypertensive drugs on 'quality of life', and it is interesting that both used captopril as a comparative drug. Although both studies differed in their 'quality of-life' definitions and in their assessment methods, in the overall analysis of change, both favoured captopril. There are no published trials comparing the effects of enalapril with other antihypertensive agents on major aspects of quality of life. Our own results show that enalapril and atenolol are equivalent, both in terms of antihypertensive efficacy and incidence of side effects. PMID- 2889812 TI - Hypertension in pregnancy. AB - Hypertensive diseases of pregnancy are clinically important because they can adversely influence the health and life of both mother and baby. Hypertensive disease is the commonest cause of maternal mortality in England and Wales, accounting for 20.4% of maternal deaths. It is depressing to note that most, if not all, of these deaths are preventable. Three broadly different kinds of hypertension can be identified as potential complications of pregnancy: chronic hypertension, pregnancy-induced hypertension (PIH) and pre-eclampsia. Where chronic hypertension is treated with methyldopa and PIH is treated with atenolol, there is evidence that therapy is beneficial in terms of immediate pregnancy outcome and is not harmful to the child. Atenolol is currently being evaluated in combination with nifedipine to treat cases of early onset of severe pre eclampsia, and preliminary results are encouraging. Prevention rather than cure should be the aim in managing hypertensive diseases during pregnancy. Early intervention can prevent serious problems later on. PMID- 2889813 TI - Beta-blockers in hypertension. AB - Following the early and important observations more than two decades ago, by Prichard and Gillam that beta-blockers had a useful antihypertensive effect, this class of compounds has become widely accepted in the treatment of elevated arterial pressure. Today there are numerous different compounds available within the beta-blocker class, with marked differences in their ancillary properties. Undoubtedly, the blockade of beta 1-adrenoceptors is the effect needed to achieve the reduction in blood pressure, and this selectivity also offers some advantages from a safety point of view. However, in some circumstances, ancillary properties such as beta 2-blockade may offer advantages, as can intrinsic sympathomimetic activity. The fact that beta-blockers have become first-line treatment for hypertension in many countries and that memoranda produced by the World Health Organization and the International Society of Hypertension jointly advocate beta blockers as one alternative for basic therapy reflects the positive balance between efficacy and side effects seen with these agents. It is also an indication that positive long-term clinical experience has been accumulated with beta-blockers. Finally, secondary prevention against coronary heart disease is well documented for beta-blockers. For this reason there have been great hopes for many years that beta-blockers would also have a primary preventive effect against coronary heart disease when used in the treatment of hypertension. Indications are now accumulating that, at least in some subgroups of patients, beta-blockers may have such an effect. Thus, although newer classes of compounds appear to be extremely competitive, beta-blockers are likely to play an important role in the treatment of hypertension for many years to come. PMID- 2889814 TI - Will the results of the recent trials influence current antihypertensive therapy? A round-table discussion. PMID- 2889815 TI - [A strongly suspected case of adult T-cell leukemia/lymphoma manifested as salivary gland tumor]. PMID- 2889816 TI - Genetic determination of mesencephalic tyrosine hydroxylase activity in the mouse. AB - The hereditary factors that affect mesencephalic tyrosine hydroxylase (TH) activity were investigated in highly inbred mouse strains (CXBI/ByJ, C57BL/6ByJ, and BALB/cJ). The progenitor strains and their F1 hybrids, were compared for mesencephalic TH activity with each other and with replicated F2 generations. Quantitative and non-parametric genetic analysis of the data raise the possibility that there is a major gene with robust additive effect that is primarily responsible for the difference between the progenitor strains with intermediate and high mesencephalic TH activity. Strain differences in mesencephalic TH activity have been linked to differences in number of dopamine (DA) neurons in that area. If genetic variation of mesencephalic TH activity is entirely attributable to variation in number of mesencephalic dopamine (DA) neurons, identification of the genetic sources of variation of mesencephalic TH activity may take us a step closer to animal models and preparations that are needed in the study of the physiological and constitutional mechanisms of human disorders in which DA neurotransmission is involved. PMID- 2889817 TI - Murine tyrosine hydroxylase maps to the distal end of chromosome 7 within a region conserved in mouse and man. AB - The locus of the structural gene encoding tyrosine hydroxylase, Th, the rate limiting enzyme for catecholamine biosynthesis, was mapped to the distal end of mouse Chromosome (Chr) 7. A DNA probe of genomic origin of rat tyrosine hydroxylase was used to detect restriction fragment length variants among 8 inbred mouse strains. The strain distribution pattern of Th allelic variants in 3 sets of recombinant inbred mouse strains was determined. Comparison of the strain distribution patterns of Th alleles with those of previously typed loci suggested Th was located on Chr 7. The Chr 7 assignment for Th was confirmed by analyzing 108 mice produced from an (NZB X SM)F1 X NZB backcross. Moreover, the Th locus was positioned distally on Chr 7. Mouse Chr 7 and human Chr 11p (the location of the human tyrosine hydroxylase gene) are known to share several homologous loci. With the addition of Th, the homology between the distal 2/3 of mouse Chr 7 and human Chr 11p appears extensive. PMID- 2889818 TI - Isolated gonadotropin deficiency in boys: clinical characteristics and growth. AB - Analysis of the clinical findings and growth in 20 boys with isolated gonadotropin deficiency revealed a heterogeneous group of physical abnormalities. Ten of these patients were hyposmic or anosmic (Kallmann syndrome). Abnormalities found in our patients included undescended testes, gynecomastia, and ocular or skeletal anomalies. Regardless of the presence of hyposmia, patients without testicular enlargement (less than 2 cm3), had serum luteinizing hormone (LH) responses to luteinizing hormone-releasing factor (LRF) that were the same as in prepubertal boys. By contrast, five boys with testicular enlargement (greater than 2 cm3), some of whom had hyposmia, had a greater serum LH response to LRF than did prepubertal boys. Adrenarche was moderately delayed; although all boys initially had normal serum levels of dehydroepiandrosterone-sulfate, four boys eventually developed elevated serum levels. Bone ages were delayed compared with chronologic age in boys who had the condition after 15 years of age. The rate of linear growth was normal, and final adult heights were normal with testosterone therapy, although linear growth continued longer in these boys than in boys with normal pubertal progression. Although none of the patients was obese at the time of diagnosis, three patients developed obesity after initiation of testosterone therapy. PMID- 2889819 TI - Treatment of acromegaly with a somatostatin analog in a patient with McCune Albright syndrome. PMID- 2889820 TI - Torsion of an undescended intraabdominal benign testicular teratoma. AB - A 4-year-old well boy was seen because of an asymptomatic left testicle undescended since birth; the testis was not palpable and the right side was normal. After an episode of left lower quadrant and left hip area pain, with some bladder symptoms and left leg limping, a work-up including a CAT scan showed a calcified retroperitoneal pelvic tumor on the left side. At laparotomy, an infarcted mass was found in the pelvis just above the internal ring. It was a torsion of an undescended intraabdominal testis with a benign testicular teratoma. The tumor was removed and his recovery was uneventful. PMID- 2889821 TI - Pediatric implications of multiple endocrine neoplasia. AB - The association of endocrine tumors from several sites has been known for over 50 years but the familial aspects of these relationships have only been appreciated since 1954. The original term multiple familial endocrine adenomatosis (MEA) was changed to multiple endocrine neoplasia (MEN). This report describes two children aged 8 and 11 years, who are cousins with MEN IIa. A strong family history prompted investigation of these children. Pentagastrin stimulation resulted in elevated serum calcitonin levels and subsequent surgery. Unsuspected medullary thyroid carcinoma was found in each child. Proper screening of high-risk individuals should prevent this potentially lethal condition from becoming a major problem. PMID- 2889822 TI - Omphalocele, cryptorchidism, and brain malformations. AB - Nineteen male infants died with a large omphalocele and 52% had associated cryptorchidism. However, two different groups with both omphalocele and cryptorchidism were recognized: (1) Eleven patients with omphalocele without brain malformation and an incidence of undescended testes not significantly different from the normal population; (2) Eight patients with omphalocele and brain malformation all having cryptorchidism. A comparison of the groups indicated that intact intraabdominal pressure during intrauterine life is not a main driving force of testicular descent, whereas normal testicular descent may occur only when the brain is normally developed. Whenever a child with omphalocele and cryptorchidism is examined, careful evaluation of the central nervous system is indicated. This triad of malformations may have prognostic and therapeutic implications. PMID- 2889823 TI - The metabolism of roxatidine acetate hydrochloride in rat and dog liver homogenates. AB - The metabolites were identified by gas chromatography-mass spectrometry (GC-MS). When an equimolar mixture of roxatidine acetate hydrochloride and its deuterated compound, labeled with ten deuterium atoms in the piperidine ring, was incubated with the 9000 X g supernatant (S-9) fraction of either rat or dog liver homogenate, the oxygenated metabolites of the piperidine ring such as the 3 hydroxypiperidine derivative (M1) and the 2-oxopiperidine derivative (M2) were isolated from rats but M2 was not isolated from dogs. These results suggested that the species differences in the metabolism of the piperidine ring in vitro are similar to that in vivo. The deuterium isotope effect (H/D) was 1.34 for M1 and 1.47 for M2 in rats, while the value for M1 in dogs was 1.69. On the other hand, the formation of these oxidative metabolites was inhibited by carbon monoxide in incubations using hepatic microsomes, suggesting that the reaction was catalyzed by cytochromes P-450. PMID- 2889824 TI - Analysis of structural requirements for the absorption of drugs and macromolecules from the nasal cavity. AB - An octapeptide and a protein, of molecular weights 800 and 34,000, respectively, were found to have nasal bioavailabilities of 73 and 0.6%, respectively, in the rat. This data, combined with reported values for 23 other compounds, indicated good availability without adjuvants for all molecules up to 1000 molecular weight (mean 70%, SD between compounds 26%, n = 15) with a decline in availability above this value. The relationship between absorption and molecular weight was modeled assuming competition between constant clearance from the nasal cavity and molecular weight-dependent transport through the mucosa. Deviations of absorption from values predicted by this model did not correlate with factors such as charge, hydrophobicity, or susceptibility to aminopeptidases, but the relative absorption of cyclic and cross-linked peptides and proteins was significantly greater than that of linear peptides. It is argued that the most likely route for transport is through junctions between cells and that surface-active adjuvants (MW 6000) which markedly enhance insulin uptake may act by rendering hydrophobic areas of contact of the junctional proteins temporarily hydrophilic. The nasal route is suitable for efficient, rapid delivery of many molecules of molecular weight less than 1000. With the use of adjuvants, this limit can be extended to at least 6000 and possibly much higher. PMID- 2889825 TI - The heavyweight runner. PMID- 2889826 TI - gamma-Aminobutyric acid-induced modulation of acetylcholine release from the guinea pig lung. AB - gamma-Aminobutyric acid (GABA) content was measured biochemically and the effect of GABA on the release of [3H]acetylcholine (ACh) was studied in strips of the guinea pig lung preloaded with [3H]choline. GABA contents were highest in the middle sections of the lung, as compared with proximal and distal areas. GABA evoked the release of [3H]ACh from the strips of the lung. The effect of GABA was mimicked by muscimol and antagonized by bicuculline and furosemide. Perfusion with Ca++-free medium and tetrodotoxin, but not nipecotic acid, inhibited the GABA- and muscimol-evoked release of [3H]ACh, thereby indicating that the released ACh was of neuronal origin. Diazepam and pentobarbital potentiated the muscimol-evoked [3H]ACh release. On the other hand, GABA reduced the KCl (40 mM) evoked release of [3H]ACh in the presence of tetrodotoxin and bicuculline and baclofen mimicked the inhibitory effect of GABA. The effects of GABA and baclofen were not altered by alpha and beta adrenergic antagonists. These findings provide evidence for two types of GABA receptors in the lung of the guinea pig, and these receptors are involved in regulating the release of ACh. PMID- 2889827 TI - Differential serotonin2 receptor recovery in mature and senescent rat brain after irreversible receptor modification: effect of chronic reserpine treatment. AB - We report here the differential time course of recovery of [3H]ketanserin-labeled serotonin2 (5-HT2) receptors in frontal cortex of mature (4 months old) and senescent (28 months old) male Fischer 344 rats. We provide evidence that the irreversible modification of 5-HT2 serotonin receptors by N-ethoxycarbonyl-2 ethoxy-1,2-dihydroquinoline occurs at the ligand binding site and that this treatment does not appear to affect the interaction of these receptors with their guanine nucleotide regulatory protein. Senescent rats exhibited significantly reduced (-20%) maximum receptor density levels of 5-HT2 receptors compared with their mature counterparts. The time course of recovery of [3H] ketanserin binding to 5-HT2 receptors after irreversible receptor modification by a single peripheral injection of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline was significantly slower in senescent rats. The slower recovery was a function of decreases in both the receptor production rate and the degradation rate constant in senescent rats compared with mature rats. Interestingly, chronic reserpine treatment resulted in a significant decrease in control maximum receptor density values in both mature (-17%) and senescent (-18%) rats. Although the receptor production rate and receptor degradation rate constants in both mature and senescent reserpinized rats were slightly decreased, there was no significant change in the overall rates of receptor recovery when compared with their respective age-matched nonreserpinized counterparts. These data indicate that both the steady state levels and "turnover" of 5-HT2 receptors are decreased in senescence and that these receptors can be down-regulated by chronic reserpine treatment. PMID- 2889828 TI - Veterans Administration Cooperative Dental Implant Study--comparisons between fixed partial dentures supported by blade-vent implants and removable partial dentures. Part I: Methodology and comparisons between treatment groups at baseline. AB - This study was conducted to determine whether fixed partial dentures supported by dental implants provide an acceptable alternative to conventional removable partial dentures in patients with Kennedy class I or class II edentulous conditions. The acceptability of the new treatment will be based on success rates, impact on the health of the remaining dentition, masticatory performance, patient satisfaction, and maintenance care and cost. The study was planned also to provide comparisons between two designs commonly used by dentists for fabricating removable partial dentures. The designs differed only in terms of the type of the retainer (clasp type) and tooth support (rest location). A total of 272 patients with Kennedy class I and class II edentulous conditions were assigned on a random basis to one of the treatment groups, 134 to receive a removable partial denture and 138 a fixed partial denture supported by a blade vent implant. All of the patients were medically screened and met prespecified criteria for oral hygiene, bone support for abutment teeth, and size of the residual ridge. Thirty-four patients were eliminated from the study before completion of their treatment. An additional six patients with early implant failures were reentered in the study and followed up as a separate group. The remaining 232 patients received comprehensive dental care, including removable partial dentures for 118 and fixed partial dentures for 114 patients. A series of examinations, radiographs, masticatory performance tests, patient satisfaction, food selection questionnaires, and dietary history were completed before initiation of the treatment, 16 weeks after the insertion of an RPD or an implant, and thereafter at 6-, 18-, 36-, and 60-month intervals. In addition, patients were seen at 6-month intervals for a recall dental examination, oral prophylaxis, plaque instructions, radiographic survey of the implant, and any needed dental treatment. The randomization stratification approach produced two treatment groups with comparable age, number of remaining maxillary and mandibular teeth, type of opposing dentition, and percent of patients with Kennedy class I and class II edentulous conditions. The mean scores of bone support, tooth mobility, and sulcular depths of abutment teeth were also similar. Significant but comparable improvements in oral hygiene and sulcular depth occurred in the two groups after treatment. The periodontal health scores at the 16-week interval serve as the baseline to measure subsequent changes in periodontal health.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2889829 TI - Design and synthesis of phosphonate inhibitors of glutamine synthetase. AB - Inhibitors 1-4 have been shown previously to undergo enzymatic phosphorylation by glutamine synthetase (GS). Phosphonates 6-9 were designed as chemically stable analogues of these phosphorylated inhibitors, incorporating either a tetrahedral sulfur group (6-8) (-S-, -SO-, -SO2-) or phosphinate (9) adjacent to methylphosphonic acid. Phosphonates 6-8 resemble the transiently stable phosphorylated methionine sulfone (2), whereas 9 resembles phosphorylated 2-amino 4-phosphonobutyric acid (4). When tested as inhibitors of glutamine synthetase from bacteria, mammals, and plants, analogue 9 proved to be the most potent, with a Ki value of 7.5 X 10(-5) M vs. the Escherichia coli enzyme. Analysis of the inhibition data for 6-9 suggests that a replacement of the oxygen bridging the tetrahedral sulfur (6-8) or phosphinate (9) and the terminal phosphate with a hydrophobic methylene drastically reduces the enzyme's affinity for inhibitors. Enhanced affinity of GS for phosphonate 9 may result from interaction of the negative charge on the phosphinate with Mn2+ at the active site. PMID- 2889830 TI - 2-Phenylpyrroles as conformationally restricted benzamide analogues. A new class of potential antipsychotics. 1. AB - 2-Phenylpyrroles were synthesized as conformationally restricted analogues of the substituted benzamide sultopride and the butyrophenones haloperidol and fluanisone. Dopamine antagonistic activity is maintained if the 2-phenylpyrrole side chain is linked to the pharmacophoric N-ethylpyrrolidine moiety of sultopride or to the 4-substituted piperazine moiety of fluanisone but is lost if the 2-phenylpyrrole is combined with the 4-substituted piperidine moiety of haloperidol. The 2-phenylpyrrole analogue 1 of sultopride is in vitro 0.25 and in vivo 3 times as potent as the parent compound. Its binding to the dopamine D-2 receptors is, in analogy to the substituted benzamides, strongly sodium dependent. The 2-(4-fluorophenyl)pyrrole analogue 5 of fluanisone is superior in vitro as well as in vivo to the corresponding benzamide 7 and the butyrophenone fluanisone. The increase in activity is not only due to a higher affinity for the D-2 receptors but also to an enhanced oral absorption (ratio po/ip = 4.5 vs 40 for the benzamide and 60 for fluanisone). Compound 5 is further characterized by a high selectivity for the D-2 receptors, in contrast to the benzamide and butyrophenone analogues (ratio D-2/alpha 1 = 60, 2.0, and 0.3, respectively). The binding to the D-2 receptors has little dependence on sodium. The 2-phenylpyrrole 5 shares with the benzamide 7 a low potential to induce catalepsy, which is in contrast to haloperidol. So, 5-(4-fluorophenyl)-2-[[4-(2-methoxyphenyl)-1 piperazinyl]methyl]pyrrole (5) is the prototype of a new class of sodium independent dopamine D-2 antagonists, which may be particularly useful as potential antipsychotics with a low propensity to induce acute extrapyramidal side effects. PMID- 2889831 TI - A genomic search for linkage of neurofibromatosis to RFLPs. AB - Our initial attempt to map NF was directed towards chromosomes 4 and 19, both of which had provided positive evidence for linkage in previous reports. This analysis showed no evidence in support of either hypothesis. Our second attempt at mapping NF was a general search of the genome, analysing a set of markers selected according to their degree of polymorphism, chromosomal location, ease of use, and availability. Data for linkage analysis were obtained from 17 multiplex families which are segregating a gene for NF. Linkage analyses were performed using PAP. Of note is the lod score of +1.17 at a recombination fraction of 0.1 between NF and the centromere of chromosome 17. PMID- 2889832 TI - Linkage of the tuberous sclerosis locus to a DNA polymorphism detected by v-abl. AB - Linkage analysis was undertaken in six families with tuberous sclerosis (TS) using a restriction fragment length polymorphism detected by v-abl. No recombinants were observed in 13 informative meioses (four phase known) giving a maximum lod score of 3.18 at zero recombination (confidence limits 0 to 0.15). This provides further evidence for the assignment of TS to 9q34 and should facilitate cloning of the structural gene, genetic counselling, and first trimester prenatal diagnosis. PMID- 2889833 TI - Testicular cancer risk in boys with maldescended testis: a cohort study. AB - Testicular maldescent is considered as a predisposing condition for development of testicular malignancy. Male subjects with a history of cryptorchidism have been suggested by some authors to have a 40 to 50 times increased risk of testis cancer. However, the magnitude of this risk is a point of considerable disagreement. Therefore, we studied the records of 506 consecutive patients hospitalized for maldescended testis from January 1949 to December 1960. Testis cancer developed in 6 patients, which when compared to the 1.3 expectant Danish incidence rate, yielded a statistically significant relative risk of 4.7 (95 per cent confidence interval 1.7 to 10.2). Thus, our study confirmed that male subjects with a history of testicular maldescent have an increased risk for testis cancer, although the magnitude of this risk was lower than suggested previously. PMID- 2889834 TI - Rhinitis and asthma. PMID- 2889835 TI - Immunologic aspects of cardiovascular disease. AB - The current classification scheme of the diverse inflammatory cardiovascular diseases permits a clinical staging and facilitates prognostic assessment and therapeutic decision making. Ultimately, improvement in the classification of and definitive therapy for these conditions awaits better definition of the interaction among specific etiologic agents, host factors, and the immune system responsible for these diseases. PMID- 2889836 TI - [Effects of gall powder on the spore-forming and enterotoxin-producing abilities of Clostridium perfringens]. PMID- 2889837 TI - [A study of the incidence of ATL (adult T-cell leukemia) and anti-ATLA (antibody to the ATL-associated antigen) in an ATL-non-endemic area]. PMID- 2889838 TI - [New therapeutic methods--technics, application, efficiency and problems- endoscopic lithotripsy. b) Laser lithotripsy]. PMID- 2889839 TI - [Diagnostic methods in adult T-cell leukemia]. PMID- 2889840 TI - [Recent development of virology: human oncogenic retrovirus]. PMID- 2889841 TI - [Early responses in urinary N-acetyl-beta-D-glucosaminidase and gamma glutamyltransferase under acute exposure to simulated 6,000 m altitude]. PMID- 2889842 TI - [A case report; ATL with acquired ichthyosis and diffuse infiltration to the myocardium]. PMID- 2889843 TI - Zoonotic implications of Hantaan-like viruses: an introduction. PMID- 2889844 TI - Epidemiology of Hantaan and related viruses. AB - Hantaan and related viruses, the causative agents of hemorrhagic fever with renal syndrome (HFRS), are significant human pathogens. Current epidemiologic evidence indicates that these pathogens are disturbed more widely than once believed, and they are likely to cause disease when man comes into close contact with infected rodents. This report summarizes the characteristics of the Hantaanp-related viruses of the genus Hantavirus including epidemiology, ecological characteristics, routes of transmission, and mechanisms of virus maintenance. PMID- 2889845 TI - Hemorrhagic fever with renal syndrome: clinical aspects. AB - Hemorrhagic fever with renal syndrome (HFRS) is an acute viral fever which typically progresses through five stages: an acute grippe, followed by hemorrhage and shock, acute renal insufficiency from tubulo-interstitial nephritis, and recovery. Death from circulatory or renal failure occurs in 5%-15% of cases. In mild or abortive forms of the disease, associated with viral strains enzootic in Scandinavia the illness is milder. Hemorrhage and shock occur with lower frequency and the fatality rate is less than 1%. Pathologic examination of HFRS cases from Asia discloses generalized congestion, hyperemia, and hemorrhage, with scattered foci of necrosis in numerous organs. Congestion and hemorrhage are most evident in the kidney medulla. Widespread microscopic evidence of capillary and vascular dysfunction is found, with endothelial cell swelling, perivascular edema, diapadesis of erythrocytes and mononuclear cell infiltration. Hemorrhage and inflammation in the renal interstitium and tubular epithelial degeneration characterize the kidney pathology. Limited data indicate pathogenic roles for cell destruction from viral infection as well as immune mediated mechanisms. No specific therapy is available. PMID- 2889846 TI - Hemorrhagic fever with renal syndrome: mode of transmission to humans. AB - Hemorrhagic fever with renal syndrome (HFRS) is a viral disease spread to humans from persistently infected rodents and other small mammals. The consensus of opinion regarding the mechanism of transmission to man indicates a principal role for respiratory infection from aerosols of infectious virus from rodent urine, feces and saliva. Interhuman, secondary spread of infection does not occur. The role of ectoparasites in virus transmission is undefined. However, epidemiologic considerations and virologic studies indicate possible roles for chiggers and gamasoid mites. PMID- 2889847 TI - Control of laboratory acquired hemorrhagic fever with renal syndrome (HFRS) in Japan. AB - By the end of 1985, 126 human cases of laboratory acquired hemorrhagic fever with renal syndrome (HFRS) were recorded in Japan. Seroepidemiological studies revealed that laboratory rats exhibited high IFA titers against Hantaan or related viruses at locations where HFRS patients occurred. Laboratory researchers contracted HFRS more frequently than laboratory animal technicians or caretakers, although a laboratory animal caretaker died of the disease. Inhalation of HFRS virus contaminated air in an animal facility is the likely cause of infection with this virus. Wound infection during animal experiments may be another important route of infection. Infection of laboratory rats can occur by transferring animals from contaminated to other animal facilities. Tissue fragments or cells of transplantable animal tumors are a potential source of spreading the HFRS virus. Eradication of HFRS virus from a contaminated animal facility can be achieved best by elimination of all animals in the room, especially when human HFRS is associated with an infected colony. In some cases, when IFA titers of the sera of the rats tested were low, infection apparently disappeared without instituting any particular control measures other than ordinary procedures for care and management of laboratory animals. HFRS viruses have not yet been eradicated from all animal facilities in Japan. Therefore, serological monitoring of laboratory rats continues. PMID- 2889848 TI - Cloning of rat "prion-related protein" cDNA. AB - Rat prion-related protein (PrP) cDNA has been cloned and sequenced. Comparison of this cDNA with those from human, hamster, and mouse indicates extremely high conservation (about 95%). The deduced partial rat PrP possesses: (a) a highly conserved region composed of repetitive sequences in what is presumably an extracellular domain, (b) a hydrophobic transmembrane domain, (c) a highly charged region which should stop membrane transfer, (d) a substantial cytoplasmic domain (which contains all of the nonconservative substitutions and a high proportion of conservative substitutions), and (e) a hydrophobic C-terminus. Dot and Northern blot analyses suggest a limited expression of PrP in rat tissues and indicate that PrP expression is decreased in the brain during the acute phase response systemically. Our results lend support to the notion that PrP is a highly conserved, normal cellular membrane protein of essential (although unknown) biologic function, which may be deposited in fibrillar amyloid form as a result of abnormal processing. PMID- 2889849 TI - A permissive role for extracellular Ca2+ in regulation of prolactin production by 1,25-dihydroxyvitamin D3 in GH3 pituitary cells. AB - A clonal strain of rat pituitary tumor cells (GH3) that spontaneously synthesizes and secretes prolactin (PRL) and growth hormone (GH) was used as model system to study the mechanism of action of 1,25-(OH)2D3. We have previously demonstrated that these cells possess specific cytosol binding proteins for 1,25-(OH)2D3 (Haug and Gautvik, 1985). When the GH3 cells were incubated in a serum-free, chemically defined medium of low extracellular Ca2+ concentration, 1,25-(OH)2D3 stimulated PRL production in a dose-dependent manner. The stimulation was detectable at 10( 11) M, and the maximum effect (2-fold increase) was observed at 10(-9) M (ED50 = 2 x 10(-11) M). The dose-response curve was bell-shaped, and at 10(-6) M 1,25 (OH)2D3 even suppressed PRL production to about 75% of controls. The stimulatory effect was first seen after 2 days and was maximal after 4 days. On a molar basis 25-OHD3 and 1-OHD3 were at least 100 times less potent than 1,25-(OH)2D3, while 24,25-(OH)2D3 had no effect on PRL production. At an extracellular concentration of Ca2+ as low as 4 x 10(-5) M the stimulatory effect of 1,25-(OH)2D3 was small (1.3-fold). Increasing extracellular Ca2+ to 1.5 x 10(-4) M increased the 1,25 (OH)2D3-induced PRL response to 2.1-fold. In contrast to the biphasic effect of 1,25-(OH)2D3 on PRL production, GH production was decreased to about 60% of controls at 10(-8) M and above. These findings indicate that in serum-free medium the stimulatory effect of 1,25-(OH)2D3 on PRL production is critically dependent on the concentration of extracellular Ca2+. PMID- 2889850 TI - Skeletal muscle relaxant action of an aqueous extract of Portulaca oleracea in the rat. AB - The aqueous extract of Portulaca oleracea produced skeletal muscle relaxation in rats following i.p. or oral administration, as assessed by the prolongation of pull-up time. The i.p. route of administration was more effective. When compared with chlordiazepoxide (20 mg/kg, i.p.), diazepam (40 mg/kg, i.p.) and dantrolene sodium (30 mg/kg, oral), the extract (200-1000 mg/kg, i.p.) proved a more effective skeletal muscle relaxant. With 1000 mg/kg i.p., 80% lethality was seen. The LD50 in an acute toxicity test in mice was 1040 mg/kg i.p. PMID- 2889851 TI - Hormonal activity of the transplanted pancreas in dogs. PMID- 2889852 TI - Allelic variation of the c-raf-1 oncogene in non-Hodgkin's lymphoma. AB - Polymorphic variation of the c-raf-1 proto-oncogene is reported here for the first time. In a study of 21 individuals, including 17 with non-Hodgkin's lymphoma and three healthy controls, we have identified three c-raf-1 alleles. One variant allele was observed in both a mother and her son, both of whom had lymphoma, but in no other case. The other variant allele was observed in two patients with lymphoma and in a healthy control. PMID- 2889853 TI - Southern blot analysis of BII cell line--a putative variant of HL-60. AB - Southern blot analysis of various genes was used to compare the human promyelocytic leukemia cell line HL-60 and the BII cell line, which reportedly arose as a spontaneous differentiation inducer-resistant variant from an HL-60 culture. Granulocyte-macrophage colony stimulating factor gene restriction fragment polymorphism, due to a partial deletion of one of the alleles of this gene in HL-60, was not observed in the BII cells. Furthermore, the p53 oncogene, most of which is deleted in the HL-60 cell line, was found to be intact in the BII cell line. Human leukocyte antigen typing revealed that the two cell lines shared the A locus but differed at the B locus. Several unique restriction fragments hybridizing to human leukocyte antigen class I and DR beta gene probes were observed in the DNA digests of each cell line. Altogether these data provide definitive evidence that BII represents a human cell line of different origin than HL-60. Further lineage determination of this cell line could add a useful member to the group of leukemic cell lines. PMID- 2889854 TI - Refinement and precision in the classification of murine lymphomas by genotyping with immunoglobulin and T cell receptor probes. AB - Of 114 murine leukemia virus induced lymphomas and 12 lymphoid hyperplasias, T cell receptor beta-chain gene and immunoglobulin gene constellation (immunogenotype) was compared with histology and surface marker expression (immunomorphology). In 53 out of 114 lymphomas (45%), definite conclusions concerning cell lineage were possible only after genotyping. Fifteen follicular center cell lymphomas with a clear phenotype (13 tumors with B and 2 tumors with T cell markers) were genotypically classified in agreement with their phenotype. Of another 21 follicular center cell tumors (12 null cell tumors lacking T or B cell-specific antigens and 9 tumors phenotypically composed of mixtures of T and B cells), B cell lineage was determined upon genotyping in 17 cases. All 41 lymphoblastic tumors with a T cell phenotype and 6 out of 7 lymphoblastic tumors with a T cell phenotype and 6 out of 7 lymphoblastic tumors with a B cell phenotype, upon DNA analysis were indeed classified as T and B cell tumors, respectively. Of another 10 lymphoblastic tumors (phenotypically 4 null cell lymphomas, 6 mixtures of T and B cells) genotyping established lineage in 9 cases. Fifteen lymphoblastic neoplasms showing lineage infidelity because of simultaneous expression of a T (Thy-1) and a B cell (B220) marker were clearly of T cell genotype. Only 4 out of 114 lymphomas tested retained both Ig and T cell receptor genes in germline configuration, although 6 lymphomas in these series had both Ig and T cell receptor genes rearranged. Four of twelve lesions histologically classified as hyperplasias nevertheless contained a monoclonal B cell population at the DNA level. Immunogenotypic evaluation of lymphomas allows precise lymphoma lineage determination even in cases where marker analysis falls short, and is clearly superior in detecting mono- or oligoclonality in lymphomas versus polyclonality in benign lesions. PMID- 2889855 TI - PCNA (cyclin) autoantibodies and monoclonal antibodies reveal similar patterns of cyclin (PCNA) antigen staining in human cultured cells. AB - Double immunofluorescence and [3H]thymidine autoradiographic analysis of the same field of transformed human amnion cells (AMA) reacted with proliferating cell nuclear antigen (PCNA) autoantibodies and a monoclonal antibody (mAb 19F4) specific for cyclin (PCNA) revealed similar patterns and sequence of cyclin (PCNA) antigen staining during S-phase. These results suggest that immunofluorescence patterns obtained with PCNA autoantibodies reflect in fact patterns of cyclin (PCNA) antigen staining. PMID- 2889856 TI - Determination of clonality in acute nonlymphocytic leukemia by restriction fragment length polymorphism and methylation analysis. AB - Determination of cellular clonality in hematological malignancies provides fundamental information that is important in understanding the pathogenesis of these disorders. We present here an extension of one approach to accomplish this that is based on the interpretation of different methylation patterns on active and inactive X chromosomes within the region of the hypoxanthine-guanine phosphoribosyltransferase gene spanned by a restriction fragment length polymorphism. The successful application of the method to determine clonality is described for three female patients with acute nonlymphocytic leukemia. PMID- 2889857 TI - The third international workshop and conference on human leukocyte differentiation antigens with an up-to-date overview of the CD nomenclature. PMID- 2889858 TI - Mid to late S-phase replication of the nucleolus in lymphoid human Molt-4 cells. AB - Indirect immunofluorescence staining of synchronized lymphoid human Molt-4 cells with proliferating cell nuclear antigen autoantibodies specific for cyclin revealed nucleolar staining only in cells in mid to late S-phase. These results together with similar earlier observations in epithelial and fibroblasts cells indicate that this organelle replicates in mid to late S-phase in cultured somatic cells. PMID- 2889859 TI - [Life environment, healing and treatment with neuroleptics in schizophrenia]. PMID- 2889860 TI - Timing of strict diet in relation to fetal damage in maternal phenylketonuria. An international collaborative study by the MRC/DHSS Phenylketonuria Register. AB - 64 infants born to women with phenylketonuria (PKU) were grouped according to the mother's dietary treatment in pregnancy. 17 infants, whose mothers were receiving a strict low phenylalanine diet and had blood phenylalanine concentrations below 600 mumol/l at the time of conception, had normal birthweights and head circumferences and no malformations. In the 29 infants whose mothers were receiving either a relaxed diet or a normal diet at conception but who started a strict diet at some time during pregnancy, birthweights and head circumferences were below those in healthy infants and there was an excess of malformations; the findings closely resembled those for the 18 infants whose mothers received no treatment during pregnancy. The birthweights and head circumferences of the 64 infants were inversely related to the maternal phenylalanine concentrations around the time of conception. Only a strict diet started before conception is likely to prevent fetal damage. PMID- 2889861 TI - Study of hereditary fructose intolerance by use of 31P magnetic resonance spectroscopy. AB - The effect of fructose on liver metabolism in patients with hereditary fructose intolerance (HFI) and in heterozygotes for HFI was studied by 31P magnetic resonance spectroscopy (31P-MRS). In patients with HFI (n = 5) ingestion of small amounts of fructose was followed by an increase in sugar phosphates and decrease in inorganic phosphate (Pi) in the liver that could be detected by 31P-MRS. 31P MRS could be used to diagnose fructose intolerance and to monitor the patients' compliance with a fructose-restricted diet. In heterozygotes (n = 8) 50 g fructose given orally led to accumulation of sugar phosphates and depletion of Pi in the liver. Fructose also induced a larger increase in plasma urate in heterozygotes than in control subjects. The effect of fructose on liver Pi and plasma urate was most pronounced in heterozygotes with gout (n = 3). Heterozygosity for HFI may predispose to hyperuricaemia. PMID- 2889862 TI - Chloramphenicol use and childhood leukaemia in Shanghai. AB - A population-based case-control interview study of 309 childhood leukaemia cases and 618 age and sex matched controls showed a significant dose-response relation between chloramphenicol and risk of both acute lymphocytic leukaemia (ALL) and acute non-lymphocytic leukaemia (ANLL), treatment for more than 10 days being associated with risks of 11.0 and 12.0, respectively. A significant risk of ANLL was also observed with the use of syntomycin, a drug pharmacologically related to chloramphenicol. The risks remained high when analyses were limited to either first or latest use of these antibiotics more than 2 years before diagnosis. Although the association may have non-causal explanations, the results warrant cautious prescribing patterns and further investigations into the leukaemogenic potential of chloramphenicol. PMID- 2889863 TI - Correlation of type A behaviour with adrenergic receptor density: implications for coronary artery disease pathogenesis. AB - In 17 healthy young men who had a parent with documented early coronary disease, ratings of type A behaviour correlated with upregulated lymphocyte beta 2 receptor density and inversely with the ratio of platelet alpha 2 to lymphocyte beta 2 receptor density ratio. This indicates a correlation of type A behaviour with receptor-based determinations of increased peripheral alpha-adrenergic balance, consistent with increased coronary arterial vasoconstriction, perhaps leading to coronary artery disease. PMID- 2889864 TI - Clinical status of IVF, GIFT, and related techniques. PMID- 2889865 TI - A poison tree. PMID- 2889866 TI - What can be done for night waking in children? PMID- 2889867 TI - Flow cytometry and gestational trophoblastic disease. PMID- 2889868 TI - A non-nuclear war; is there no alternative? PMID- 2889869 TI - Energy requirements of pregnancy in The Netherlands. AB - 57 healthy Dutch women were studied longitudinally from early pregnancy until 2 months post partum. Regular measurements were made of energy intake in food, basal metabolic rate, body weight and body fat mass, and levels of physical activity. Some data were obtained before conception in 23 women. The energy cost of pregnancy calculated as the energy deposited as new tissues plus the associated increase in basal metabolism amounted to 286 MJ (1020 kJ/day), which is only 11% lower than the theoretical estimate of requirements of 323 MJ (1 MJ = 239 kcal). Energy intake throughout the first 10 wk of pregnancy was identical to that before pregnancy. Energy intake was only 200 kJ/day higher in late than in early pregnancy (not significant), and the cumulative increase in energy intake over pregnancy was estimated as 22 MJ (about 80 kJ/day). There is, therefore, an energy gap in pregnancy of about 940 kJ/day. It is proposed that the main mechanisms by which the pregnant body is able to save energy and to bridge the energy gap are by adjustments to physical activity and an increase in work efficiency and an adaptation of the metabolic response to food. Savings on physical activity by behavioural adaptations will not exceed 355 kJ/day. PMID- 2889870 TI - Criteria for severe aplastic anaemia. AB - To study the validity of currently accepted international criteria for severe aplastic anaemia, 213 consecutive cases of bone marrow aplasia from a single institution were analysed. The distribution percentiles of peripheral blood values and multivariate analysis showed that the current reticulocyte count limit of 1% (corrected for haematocrit) is inadequate an an indicator of severe disease and should be substantially lowered. Since the choice of treatment in aplastic anaemia may depend on the prognosis current criteria for severe aplastic anaemia should be modified. PMID- 2889871 TI - What should be done about smallpox virus? PMID- 2889872 TI - Triple and quadruple immunosuppressive therapy in organ transplantation. PMID- 2889873 TI - Fibronectin as possible adjunct in treatment of severe malnutrition. PMID- 2889874 TI - Therapeutic range of cyclosporin in renal transplant patients by specific monoclonal radioimmunoassay. PMID- 2889875 TI - Cyclosporin-induced dysmorphic changes in the BB/W rat. PMID- 2889876 TI - Myopia and cataract. PMID- 2889877 TI - Real-time NMR imaging of coronary vessels. PMID- 2889878 TI - "Sciatica" and lumbosacral disc prolapse. PMID- 2889879 TI - Diabetes-associated peptide. PMID- 2889880 TI - Hypoglycaemia unawareness. PMID- 2889881 TI - "Main-street" diabetes in West Africa. PMID- 2889882 TI - Correction of hypokalaemia via oral route. PMID- 2889883 TI - Non-steroidal anti-inflammatory drugs and perforated peptic ulcer. PMID- 2889884 TI - Angioscopy and intra-operative coronary laser angioplasty. PMID- 2889885 TI - Exercise-induced hypotension. PMID- 2889886 TI - How far to lower blood pressure? PMID- 2889887 TI - Cholesterol, ghee, and atherosclerosis. PMID- 2889888 TI - Doxycycline prophylaxis for malaria. PMID- 2889889 TI - Steroids and Pneumocystis carinii pneumonia. PMID- 2889890 TI - Steroids for pneumonitis after bone-marrow transplantation. PMID- 2889891 TI - Aerosolised pentamidine. PMID- 2889892 TI - Clinical case definition of AIDS in African adults. PMID- 2889893 TI - Increasing HIV-2-associated AIDS in Senegal. PMID- 2889894 TI - Speed and central venous lines. PMID- 2889895 TI - Faecal bile acids, dysplasia, and carcinoma in ulcerative colitis. PMID- 2889896 TI - Contemporary growth charts. PMID- 2889897 TI - Intrauterine growth retardation: prediction of perinatal distress by Doppler ultrasound. PMID- 2889898 TI - Aspirated stool samples from infants with gastroenteritis. PMID- 2889899 TI - Venous occlusion and estimation of serum constituents. PMID- 2889900 TI - Timentin resistance. PMID- 2889901 TI - Bladder instability or urethral causes? PMID- 2889902 TI - Epidermal cells in culture. PMID- 2889903 TI - Baking soda and pruritus. PMID- 2889904 TI - Carcinoma-in-situ of the testis. PMID- 2889905 TI - Protective effect of oestrogen in pancreatic cancer. PMID- 2889906 TI - Anticardiolipin antibodies and occlusion of coronary artery bypass grafts. PMID- 2889907 TI - An epidemic of abortion bills. PMID- 2889908 TI - What makes some children short-sighted? PMID- 2889910 TI - The University of Chile in crisis. PMID- 2889909 TI - Hyperprolactinaemia; when is a prolactinoma not a prolactinoma? PMID- 2889911 TI - Gynecological ultrasound. PMID- 2889912 TI - Of cabbages and queens. PMID- 2889913 TI - Intervention for fetal obstructive uropathy: has it been effective? AB - The best management of fetal hydronephrosis is controversial. Despite the lack of experimental evidence that prenatal drainage of the obstructed urinary tract substantially improves ultimate renal function, various forms of percutaneous intervention on the fetal bladder and kidney have been used. To evaluate the efficacy of intervention for suspected fetal obstructive uropathy, all published reports of drainage of the fetal urinary tract up to December, 1985, were reviewed. In the 57 reported cases, the most common type of intervention was placement of a vesicoamniotic shunt (37%). Complications occurred in 25 cases (44%), including inadequate shunt drainage or migration (19%), onset of premature labour within 48 h (12%), urinary ascites (7%), and chorioamnionitis (5%). Of 28 fetuses with associated oligohydramnios, only 6 (21%) survived. 2 of these survivors had vesicoamniotic shunts, 2 single or multiple bladder aspirations, 1 an external renal drainage catheter, and 1 in-utero vesicostomy. Because of the high complication rate and lack of evidence of improved survival from in-utero drainage procedures, a prospective, randomised trial is needed to compare survival with and without vesicoamniotic shunt placement. PMID- 2889914 TI - Energy requirements of pregnancy in rural Thailand. AB - The energy cost of pregnancy was measured in rural Thai women between 10 wk gestation and term. The energy cost of pregnancy, which includes the increase in basal metabolic rate (BMR), the energy equivalent of maternal fat laid down, and the assumed energy equivalent of fetal fat and fetal and maternal protein, was 202 MJ (1 MJ = 239 kcal). BMR increased by 100 MJ overall and maternal fat gain averaged about 1.3 kg, equivalent to 60 MJ. The energy cost was more than covered by an overall increase in food intake of 238 MJ with little evidence of any complementary reduction in total energy expenditure by reduced physical activity. PMID- 2889915 TI - Decreased mortality among male prisoners. AB - The mortality among a population of male prisoners between 1977 and 1983 was compared with that among the general French population. The overall mortality rate (for all deaths except external causes) was lower among prisoners (SMR = 84; p less than 0.05). Moreover, the risk of dying from all causes, as well as from malignant neoplasms, diseases of the circulatory system, and suicides fell significantly with increasing duration of imprisonment. These findings suggest that the lifestyle specific to imprisonment might overcome the prejudicial effect of risk factors such as alcohol, tobacco, or drug abuse that tend to be common among prisoners. PMID- 2889916 TI - Institutional ethics. PMID- 2889917 TI - Child sexual abuse. PMID- 2889918 TI - Warts and diagnosis of sexual abuse. PMID- 2889919 TI - Myocardial magnesium content, histology, and antiarrhythmic response to magnesium infusion. PMID- 2889920 TI - Focal glomerulosclerosis in neonatal kidney grafts. PMID- 2889921 TI - Azathioprine and myasthenia gravis. PMID- 2889922 TI - Epidemic regional jejunitis: a new clinical entity? PMID- 2889923 TI - Vascular assessment before amputation. PMID- 2889924 TI - Lack of serum immune response to Blastocystis hominis. PMID- 2889925 TI - Evidence for catch-up growth in adolescence. PMID- 2889926 TI - Repetition strain injury. PMID- 2889927 TI - Adverse reactions to duplex scanning. PMID- 2889928 TI - Successful removal of anti-phospholipid antibody during pregnancy using plasma exchange and low-dose prednisolone. PMID- 2889929 TI - Heart transplantation for peripartum cardiomyopathy. PMID- 2889930 TI - Declines in proportion of Kaposi's sarcoma among cases of AIDS in multiple risk groups in New York City. PMID- 2889931 TI - Latency preceding seroconversion in sexually transmitted HIV infection. PMID- 2889932 TI - Castanospermine and other plant alkaloid inhibitors of glucosidase activity block the growth of HIV. PMID- 2889933 TI - Characteristic rash associated with staphylococcal pneumonia. PMID- 2889934 TI - Hyperphenylalaninaemia in parenterally fed newborn infants. PMID- 2889935 TI - Smoking and polycythaemia. PMID- 2889936 TI - Alcohol and medical education. PMID- 2889937 TI - Medical Research Council Questionnaire on Respiratory Symptoms (1986) PMID- 2889938 TI - Faith healers in the mental health team. PMID- 2889939 TI - Magnetic resonance imaging as a clinical service. PMID- 2889940 TI - Coronary heart disease mortality rates. PMID- 2889941 TI - Brain copper in Wilson's disease. PMID- 2889942 TI - Hepatotoxicity due to bindazac. PMID- 2889943 TI - Ploidy as prognostic determinant in pancreatic cancer. PMID- 2889944 TI - Plasma viscosity changes after sham plasmapheresis. PMID- 2889945 TI - Laser photovaporisation and menorrhagia. PMID- 2889946 TI - Pre-eclampsia and trisomy 13. PMID- 2889947 TI - Hyperventilation and anaesthetic requirement in babies. PMID- 2889948 TI - Pain and awareness during general anaesthesia. PMID- 2889949 TI - Monitoring for anaesthesia. PMID- 2889950 TI - Difficult intubation. PMID- 2889951 TI - Antigliadin and antireticulin antibodies in coeliac disease and at onset of diabetes in children. PMID- 2889952 TI - Cytopathic effect of verotoxin on endothelial cells. PMID- 2889953 TI - Lactate dehydrogenase isoenzyme 1 in testis cancer. PMID- 2889954 TI - Erythromycin and gastrointestinal motility. PMID- 2889955 TI - Management of dyspepsia. PMID- 2889956 TI - Informed consent: a Canadian case in a British perspective. PMID- 2889957 TI - Reduced morbidity from skeletal metastases in breast cancer patients during long term bisphosphonate (APD) treatment. AB - 131 patients with osteolytic metastases from breast cancer were randomised to receive long-term oral treatment with aminohydroxy-propylidene-bisphosphonate (APD), 300 mg daily (n = 70), or to act as controls (n = 61) in a multicentre trial. Specific antitumour therapy was at the discretion of the clinician and variable. An interim analysis was made after a median follow-up of 13 months in the APD group and 14 months in the controls. There was a significant reduction in pathological fractures and severe bone pain in the APD group, and hypercalcaemia was prevented. Consequently the necessity for radiotherapy for skeletal complications was more than halved; the number of systemic therapy changes was also reduced. Gastrointestinal side-effects of APD led to a drop-out of 8% of patients. Oral supportive APD therapy is simple and convenient, and significantly reduced skeletal morbidity in advanced breast cancer. PMID- 2889958 TI - Effects of changes in smoking and other characteristics on clotting factors and the risk of ischaemic heart disease. AB - The Northwick Park Heart Study (NPHS) has demonstrated associations of high levels of factor VII coagulant activity (VIIc) and of plasma fibrinogen concentration with the risk of subsequent ischaemic heart disease (IHD). In cross sectional data from the 2023 white men in NPHS, lifetime duration of smoking was a determinant of initial plasma fibrinogen levels. Fibrinogen levels had apparently begun to fall soon after smoking was discontinued but it was over 5 years before they had returned to levels found in life-long non-smokers. In prospective data, smoking cessation and the adoption or resumption of smoking were associated with a decrease or an increase, respectively, of about 0.15 g/l in plasma fibrinogen. These changes would lower or raise the risk of IHD by about 20%. A switch from cigarettes to cigars was associated with a large increase in fibrinogen. A substantial part of the relation between smoking and IHD appears to be mediated through the fibrinogen concentration. Following changes in body mass, VIIc rose in those who had given up smoking and fell in those who resumed. PMID- 2889959 TI - Genetic and cultural inheritance of plasma fibrinogen concentration. AB - Genetic and cultural heritability of plasma fibrinogen concentration was estimated by path analysis with environmental indices in 85 families identified by means of probands with early myocardial infarction and in 85 families randomly selected from the general population. A substantial proportion of the variance of the plasma fibrinogen level, 51%, was accounted for by genetic heritability, whereas the cultural heritability was negligible. No intergenerational differences were indicated in genetic or cultural heritability. The combined effect of obesity and smoking was found to explain 3% of the variance of the plasma fibrinogen level. The demonstration of such substantial genetic control further supports the view that plasma fibrinogen is a primary risk factor for CHD rather than a reflection of the severity of manifest disease. PMID- 2889960 TI - Effect of symptomless bacteriuria in childhood on subsequent pregnancy. AB - The outcome of 52 pregnancies in 34 women who had had bacteriuria in childhood was compared with that of normal control pregnancies. The prevalence of bacteriuria at the first antenatal visit was significantly higher (p less than 0.001) in previously bacteriuric women (35%) than in controls (5%), and acute pyelonephritis developed in 10% compared with 4% of controls. Pre-eclampsia (arterial pressure above 140/90 mm Hg with proteinuria above ++) developed in 4 of 12 previously bacteriuric women known to have renal scarring (5 of 16 pregnancies), in only 1 of 22 previously bacteriuric women without scars (1 of 36 pregnancies), and in 1 of 52 controls (p less than 0.001). Women with renal scars were also more likely to undergo induction of labour (44% of pregnancies) and operative delivery (57% of pregnancies) than previously bacteriuric mothers without scars (17%, 22%) or control mothers (16%, 20%). The infants of previously bacteriuric mothers were not significantly smaller than those of healthy control mothers, but Apgar scores were lower among offspring of previously bacteriuric mothers with scarred or normal kidneys (p less than 0.001). Fetal outcome was, however, satisfactory in all cases. PMID- 2889961 TI - Increased permeability of hamster microcirculation to glycosylated albumin. AB - The permeability of the microcirculation to native and glycosylated albumin was tested in 25 non-diabetic Syrian hamsters. The microvasculature of the cheek pouch was studied by a fluorescent video-microscopy technique after the animals had been injected with fluorescent native or glycosylated albumin or with both. Native albumin remained in the cheek pouch microvasculature, whereas glycosylated albumin leaked out of the microvascular bed along the postcapillary and collecting venules. The extravascular leakage of glycosylated albumin, probably due to its electrical or conformational change, may represent the initial event in the development of diabetic microangiopathy. PMID- 2889962 TI - Is cytomegalovirus interstitial pneumonitis in transplant recipients an immunopathological condition? AB - The conventional explanation for the high fatality rate due to cytomegalovirus (CMV) pneumonitis among allogeneic transplant recipients is that immunosuppression renders the host unable to control replication of this opportunistic agent. However, evidence from studies in man and the murine model of CMV show that virus replication in the lung is unrelated to the development of pathological effects, and that a host immune response is required for the induction of pneumonitis. Thus the hypothesis is that limited CMV replication in the lungs leads to display of a virus-coded protein, which is recognised by host T-cells, and that the pneumonitis is due to an uncontrolled accumulation and recruitment of such cells in the lungs. The reason why CMV is found in the lungs of patients with the acquired immunodeficiency syndrome (AIDS) without producing pneumonitis is probably because these patients cannot mount the pathogenic T-cell response. According to the hypothesis stated here, if the immune capabilities of AIDS patients can be restored, life-threatening CMV pneumonitis may develop. PMID- 2889963 TI - Neutrophils from subjects with chronic obstructive lung disease show enhanced chemotaxis and extracellular proteolysis. AB - Peripheral polymorphonuclear leucocytes (PMN) from subjects with emphysema or bronchiectasis digested significantly more iodine-125-labelled fibronectin (on average, 250% and 280%, respectively) than did those from control subjects. PMN from patients with bronchiectasis contained significantly more of the serine proteinase elastase than did the control cells, which may have contributed to their greater extracellular proteolysis. PMN from patients with emphysema, but not those with bronchiectasis, showed enhanced chemotaxis (on average 260%) in response to a chemotactic peptide compared with control cells. Thus, PMN from subjects with chronic obstructive lung diseases can digest more extracellular connective tissue protein than PMN from healthy subjects. This behaviour suggests a mechanism for the pathological tissue damage associated with these disorders. Furthermore, the sensitivity to chemotactic factors of PMN from emphysematous patients would contribute to the larger numbers of these cells in their lung tissues, thus increasing further the proteolytic burden in the lungs. PMID- 2889964 TI - Oesophageal varices associated with busulphan-thioguanine combination therapy for chronic myeloid leukaemia. AB - 5 patients receiving continuous busulphan and 6-thioguanine for chronic myeloid leukaemia (CML) were found to have oesophageal varices associated with abnormal liver function tests. 3 of these cases presented with gastrointestinal haemorrhage and 1 patient died. The 2 other cases had varices discovered at endoscopy. Nodular regenerative hyperplasia (NRH) of the liver was identified as the cause of portal hypertension in the 4 patients on whom liver biopsies were done. The administration of busulphan and thioguanine in combination is likely to be associated with the development of NRH, with portal hypertension and oesophageal varices occurring in a substantial proportion of cases. PMID- 2889965 TI - High rate of Plasmodium vivax relapse following treatment of falciparum malaria in Thailand. AB - Within two months of treatment for falciparum malaria, Plasmodium vivax infections developed in 58 (33%) of 174 patients who had received a quinine or quinidine regimen and in 46 (32%) of 145 patients who had received mefloquine with inpatient follow-up of more than six weeks. The time to vivax relapse was significantly longer after mefloquine treatment (median 47 days, range 30-65) than after quinine or quinidine treatment (21 days, 15-36; p less than 0.0001). All patients remained outside areas of malaria transmission. These findings suggest a very high rate of double infection in Thailand with acute suppression of vivax by falciparum malaria, and warrant evaluation of radical therapy with primaquine in certain patients with acute falciparum malaria. PMID- 2889966 TI - Procollagen type I production by hepatocytes: a marker of progressive liver disease? AB - The presence of collagen-producing cells and its relation to disease activity were determined in cryostat liver tissue sections from subjects with active cirrhosis (n = 15), inactive cirrhosis (n = 5), chronic persistent hepatitis (n = 8), or normal histology (n = 3) by means of an immunofluorescence technique using a monoclonal antibody to the carboxy-terminal domain of procollagen type I (anti Pc). In all patients with active cirrhosis hepatocytes showed a strong intracellular staining with anti-Pc; in 4 of them bileducts also showed a membrane-like reaction. By contrast, tissue sections from chronic inactive liver disease and normal liver were essentially negative. These findings suggest that in chronic liver disease hepatocytes and sometimes biliary epithelium produce collagen and that production is related to disease activity. The detection of active production of procollagen type I by hepatocytes could become a useful marker of progressive liver disease. PMID- 2889967 TI - Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. AB - The adhesion of human platelets to monolayers of bovine endothelial cells in culture was studied to determine the role of endothelium-derived nitric oxide in the regulation of platelet adhesion. The adhesion of unstimulated and thrombin stimulated platelets, washed and labelled with indium-111, was lower in the presence than in the absence of bradykinin or exogenous nitric oxide. The inhibitory action of both bradykinin and nitric oxide was abolished by haemoglobin, but not by aspirin, and was potentiated by superoxide dismutase to a similar degree. It is suggested that the effect of bradykinin is mediated by the release of nitric oxide from the endothelial cells, and that nitric oxide release contributes to the non-adhesive properties of vascular endothelium. PMID- 2889968 TI - Crack. PMID- 2889969 TI - Airs, waters, places. PMID- 2889970 TI - Scrotal ultrasonography. PMID- 2889971 TI - Telling patients about their medicines. PMID- 2889972 TI - Commissioning international health. PMID- 2889973 TI - Calcium and chronic liver disease. PMID- 2889974 TI - Pain relief in polycystic kidney disease. PMID- 2889975 TI - Changing association between community occupational structure and ischaemic heart disease mortality in the United States. AB - The changing association between community occupational structure and ischaemic heart disease mortality in white men and women of the United States from 1968 to 1982 has been investigated. Occupational structure was represented by the proportion of workers in white-collar jobs. A negative association, with lower mortality in communities with higher levels of white-collar employment, emerged over the period in both men and women. The results for men may be interpreted as suggesting a recapitulation in the US of the changing association between social class and heart disease observed in Britain. Occupational structure, however, reflects resources and opportunities in a community derived from its contribution to the national and international economy. Thus the growing inequalities in heart disease mortality presented in this ecological study relate more appropriately to communities than to individual workers. PMID- 2889976 TI - Tamoxifen and benign breast problems. AB - The agent tamoxifen plays an important part in the treatment of breast cancer. Although it acts as an antioestrogen by binding to oestrogen receptors, it also has oestrogen agonistic effects on the liver. Recent toxicity studies in rats have revealed that after high dosages both cataracts and hepatocellular carcinomas develop. For these reasons it has been suggested that use of tamoxifen be discontinued for the treatment of benign conditions such as severe cyclical mastalgia and also for trials on the prevention of breast cancer. It is argued that the development of hepatocellular carcinomas in rats is the result of the known oestrogen agonist activity of tamoxifen, with similar results being found in a few women receiving oral contraceptives, the use of which still continues. Studies of the use of the agent for benign conditions should evolve in the context of controlled clinical trials in order that important new indications for tamoxifen are not overlooked. PMID- 2889977 TI - Energy requirements of pregnancy in The Gambia. AB - At most times of the year adjustments in maternal energy expenditure and energy balance in rural Gambian women can provide sufficient energy to sustain reasonable rates of fetal growth without an increase in food intake, although this study suggests that the overall level of energy intake has been substantially underestimated in the past. At certain times of year, however, pre harvest food shortages and the energy demands of subsistence farming did substantially reduce maternal fat stores and fetal growth. Dietary supplementation, already known to increase birthweight, also had measurable effects on the mothers' physiology, resulting in increased energy expenditure on basal metabolism and improving maternal fat deposition. These findings suggest that the precise energy cost of pregnancy varies as a function of the additional energy intake consumed at this crucial period. PMID- 2889978 TI - Independent International Commission on Health Research for Development. PMID- 2889979 TI - Information for patients about medicines. PMID- 2889980 TI - Are benzodiazepines useful in anxiety? PMID- 2889981 TI - Violent crime and occupational exposure to organic solvents. PMID- 2889982 TI - ACE inhibitors, atheroma, and renal function. PMID- 2889983 TI - Flavone-8-acetic acid inhibits ristocetin-induced platelet agglutination and prolongs bleeding time. PMID- 2889984 TI - Screening for neuroblastoma. PMID- 2889985 TI - Zinc, glutamate receptors, and motoneurone disease. PMID- 2889986 TI - Recombinant erythropoietin and blood pressure. PMID- 2889987 TI - Barrett's oesophagus and colon cancer. PMID- 2889988 TI - Razoxane and acute promyelocytic leukaemia. PMID- 2889989 TI - Preprandial intranasal insulin as adjuvant therapy in type II diabetics. PMID- 2889990 TI - Combination of recombinant interferons alpha and gamma in treatment of chronic hepatitis B. PMID- 2889991 TI - Liver transplantation for primary hepatic cancer in childhood. PMID- 2889992 TI - "Guiding" echotomography before percutaneous liver biopsy. PMID- 2889993 TI - Plugging liver biopsy sites with coagulation factors. PMID- 2889994 TI - Naltrexone and bulimic symptoms. PMID- 2889995 TI - Yohimbine and psychogenic impotence. PMID- 2889996 TI - Linked DNA markers in clinical diagnosis of juvenile Huntington's disease. PMID- 2889997 TI - Bartholin's abscess associated with Eikenella corrodens. PMID- 2889998 TI - Eikenella corrodens and intrauterine contraceptive device. PMID- 2889999 TI - Hypertension in the puerperium. PMID- 2890000 TI - Multiple pregnancy and assisted reproduction. PMID- 2890001 TI - Gaza's health services. PMID- 2890002 TI - Pathophysiology of akathisia. PMID- 2890003 TI - Live attenuated oral rotavirus vaccine. PMID- 2890004 TI - Aerosolised pentamidine treatment at home. PMID- 2890005 TI - Interferon-alpha in sera of HIV-infected patients. PMID- 2890006 TI - Immunoblot test with recombinant HIV antigens. PMID- 2890007 TI - Langerhans cells as primary target cells for HIV infection. PMID- 2890008 TI - Myelofibrosis with myeloid metaplasia and history of malaria. PMID- 2890009 TI - Pica, paper, and pseudoporphyria. PMID- 2890010 TI - Treatment for myelodysplastic syndromes. PMID- 2890011 TI - Lipid delivery and catheter obstruction during cyclic total parenteral nutrition. PMID- 2890012 TI - Serum cholesterol and cancer in the NHANES I epidemiological follow-up study. PMID- 2890013 TI - Tuberous sclerosis and ABO. PMID- 2890014 TI - No association between griseofulvin and conjoined twinning. PMID- 2890015 TI - Warning on plasma oestradiol measurement. PMID- 2890016 TI - Free fatty acids during extracorporeal circulation: the role of heparin. PMID- 2890017 TI - Child sexual abuse: disclosure of medical records and consent to examination for purposes of police investigation. PMID- 2890018 TI - Outcome in patients on continuous ambulatory peritoneal dialysis and haemodialysis: 4-year analysis of a prospective multicentre study. AB - In a study in seven large renal units in England, the morbidity and mortality of all patients starting continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis during 1983-85 were monitored prospectively over a 4-year period and related to reasons for choice of therapy and potential risk factors. 610 new patients (median age 52 years, range 3-80 years) started CAPD; 16% had diabetes mellitus and 21% cerebrovascular or cardiovascular disease. 329 patients (median age 48 years, range 5-77 years) started haemodialysis; 7% had diabetes mellitus and 17% cerebrovascular or cardiovascular disease. The Kaplan-Meier patient survival estimates at 4 years were 74% for haemodialysis and 62% for CAPD; technique survival figures for the same period were 91% for haemodialysis and 61% for CAPD. Cox's proportional hazards regression analysis showed that cerebrovascular/cardiovascular disease, age over 60 years, and diabetes mellitus were important predictors for survival in CAPD patients; there were no risk factors associated with permanent change to haemodialysis. In the haemodialysis group early change to CAPD was associated with presence of cerebrovascular or cardiovascular disease. The major cause of drop-out in both groups was transplantation. The mean length of hospital admission was 14.8 days per patient year for CAPD and 12.4 days per patient-year for haemodialysis. PMID- 2890019 TI - Campylobacter pylori and recurrence of duodenal ulcers--a 12-month follow-up study. AB - In 39 patients with endoscopically healed duodenal ulcers repeat endoscopy and two antral biopsies after 1 year showed a relapse rate of 59%. Only post treatment Campylobacter pylori status was a significant predictor of endoscopic relapse. 79% of patients who remained culture positive had a relapse, compared with 27% of culture-negative patients. Relapse was more likely (66%) in patients with a recurrence of C pylori after apparent eradication of the organism than in those who remained negative for C pylori (10%). No patient who remained negative for C pylori had histological gastritis, whereas all with recurrence of C pylori showed histological gastritis. These findings suggest an important role for C pylori in duodenal ulcer relapse in the year after treatment. PMID- 2890020 TI - Hypersensitivity to G2 chromatid radiation damage in familial dysplastic naevus syndrome. AB - Skin fibroblasts from 25 members of nine kindreds with familial dysplastic naevus syndrome (DNS), 12 apparently normal spouses, and 11 additional unrelated normal individuals were tested for G2 cell-cycle phase sensitivity to ionising radiation. The cells from individuals with DNS or hereditary cutaneous malignant melanoma with DNS (HCMM/DNS) had significantly more chromatid breaks and gaps when entering metaphase 0.5-1.5 h after G2 phase X-irradiation (1 Gy) than those from unaffected controls. In two cases, the test results positively identified individuals before the clinical diagnosis of DNS. A clinically normal obligate carrier of the HCMM/DNS gene showed the enhanced G2 radiosensitivity. Moreover, in a test on 1 proband, the sensitivity was apparent in peripheral blood lymphoblasts. Enhanced G2 chromatid radiosensitivity may be a marker of genetic susceptibility to HCMM/DNS. PMID- 2890021 TI - Angiotensin-converting enzyme and the cough reflex. AB - The effect of inhibition of angiotensin-converting enzyme (ACE) on standard cough challenge was investigated in a double-blind, randomised study in sixteen normal volunteers. Captopril (25 mg) or matched placebo was given by mouth 2 h before inhalation of nebulised distilled water, citric acid, and incremental doses of capsaicin (0.5-20 mumol/l). Distilled water and citric acid challenge were not significantly changed by captopril pretreatment. However, captopril significantly shifted the dose-response curve to capsaicin inhalation. The geometric mean dose of capsaicin causing 20 coughs/min was 1.3 mumol/l for captopril and 2.8 mumol/l for placebo pretreatment (p = 0.04). Cough is a recognised side-effect of ACE inhibitors; the observation that cough challenge is changed by these drugs in normal subjects implies a role for ACE in the cough reflex, possibly by metabolism of substrates other than angiotensin I. PMID- 2890022 TI - HLA-DQ beta-chain polymorphism in HLA-DR4 haplotypes associated with rheumatoid arthritis. AB - With a cDNA probe for the DQ beta gene, two variants of the DR4-linked DQw3 (3.1 and 3.2) allele were analysed in patients with rheumatoid arthritis (RA), healthy individuals, and homozygous cell lines. The DQw3.1 allele, identified by 3.4 kb (HindIII), 2.3 kb (SstI), and 3.7 kb and 6.9 kb (BamHI) restriction fragment lengths, was expressed in 100% (of 18) DR4-positive patients, compared with only 19% (of 16) of DR4-positive controls including one of five homozygous cell lines. This DQ beta variant showed a highly significant association (relative risk = 78; p less than 10(-6) with RA and may therefore play an important part in susceptibility to RA. PMID- 2890023 TI - Aching muscles after exercise. PMID- 2890024 TI - Treating Reiter's syndrome. PMID- 2890025 TI - Endoscopic laser resection in inoperable tracheobronchial and oesophageal tumors. PMID- 2890026 TI - CAPD--the white knight? PMID- 2890027 TI - Research in conflict with teaching. PMID- 2890028 TI - Energy requirements of pregnancy in the Philippines. AB - 40 rural Philippine women were studied longitudinally from 11-16 wk pregnancy until 3 months post partum. Energy intake, body weight, fat mass, basal metabolic rate (BMR), and physical activity patterns were recorded every 6 wk. The cumulative energy cost of pregnancy over the second and third trimesters of pregnancy was 189 MJ (1130 kJ/day). There was no increase in energy intake, rather a very small reduction over the final two trimesters. Changes in physical activity provided part of the estimated energy needs (375-415 kJ/day throughout the second and third trimesters of pregnancy). These measurements leave an unexplained deficit of at least 700 kJ/day. Nevertheless, there was an adequate mean birthweight (2885 g) and a 10% incidence of low birthweight. The findings seem to suggest that pregnancy outcome can be successful despite marginal energy intake. PMID- 2890029 TI - Energy requirements of pregnancy: an integration of the longitudinal data from the five-country study. PMID- 2890030 TI - Nurses in the Transfusion Service. PMID- 2890031 TI - The so-called 10-day rule. AB - The 10-day option aimed at restricting all radiography of potentially fertile women to the first third of the menstrual cycle was introduced in 1959 without any valid supporting evidence. No earlier or later experimental evidence has indicated that diagnostic radiography involving the early embryo might carry a measurable risk to the individual developing in utero. PMID- 2890033 TI - Radiation, cancer risk, and the new dosimetry. PMID- 2890032 TI - Bile acids in health and disease. PMID- 2890034 TI - Atenolol in irritable bowel syndrome. PMID- 2890035 TI - Somatostatin and symptomatic relief of irritable bowel syndrome. PMID- 2890036 TI - Ghee, cholesterol, and heart disease. PMID- 2890037 TI - Overwhelming myocarditis due to Cryptococcus neoformans in an AIDS patient. PMID- 2890038 TI - Aerosolised pentamidine. PMID- 2890039 TI - Surgery and risk of AIDS in HIV-positive patients. PMID- 2890040 TI - Transabdominal placental biopsy. PMID- 2890041 TI - Phenytoin infusion in severe pre-eclampsia. PMID- 2890042 TI - Colposcopy of women with cervical HPV type 16 infection but normal cytology. PMID- 2890043 TI - Colonoscopy or barium enema as initial investigation of colonic disease. PMID- 2890044 TI - Loss of bileducts after liver transplantation. PMID- 2890045 TI - Piezoelectric lithotripsy of gallstones. PMID- 2890046 TI - Cocaine and acute porphyria. PMID- 2890047 TI - Dark urine after extracorporeal shock-wave lithotripsy. PMID- 2890048 TI - Doctors and the death penalty. PMID- 2890049 TI - Drop-outs from clinical trials. PMID- 2890050 TI - Exchanging kidney transplants. PMID- 2890051 TI - Dyspepsia: the dilemma. PMID- 2890052 TI - Tropical ulcers. PMID- 2890053 TI - Stroke due to intravascular coagulation in Mycoplasma pneumoniae infection. PMID- 2890054 TI - Testicular cancer in leather tanners exposed to dimethylformamide. PMID- 2890055 TI - Isotretinoin dose and teratogenicity. PMID- 2890056 TI - Inherited deletion at Duchenne dystrophy locus in normal male. PMID- 2890057 TI - In-situ hybridisation of the beta-amyloid protein probe to chromosome 9 in patients with familial Alzheimer's disease. PMID- 2890058 TI - Diagnosis of cystic fibrosis. PMID- 2890059 TI - Longitudinal serological study of rubella immunity in South Yorkshire. PMID- 2890060 TI - Brazilian purpuric fever, Haemophilus aegyptius, and endotoxin. PMID- 2890062 TI - Fish oils in rheumatoid arthritis. PMID- 2890061 TI - CAWD or COLD? PMID- 2890063 TI - Cystic fibrosis and ileal carcinoma. PMID- 2890064 TI - Stable isotope dilution method for diagnosis of medium chain acyl-CoA dehydrogenase deficiency. PMID- 2890065 TI - Interpretation of "serious professional misconduct": changing the rules. PMID- 2890066 TI - [Results of follow-up of operations in pediatric patients with indirect inguinal hernia]. AB - This paper present the results of follow-up examinations of 2801 operated inguinal hernias. In comparison with the high excision of the hernial sac plus "crude suture", the standard Bassini technique produces poorer results as regards recurrence, testicular atrophy and secondary maldescent. The mortality of elective herniotomy was 0.016% in this series. PMID- 2890067 TI - [Health risks of estrogen medication?]. PMID- 2890068 TI - [Prognosis and assessment of the degree of disability in hip joint endoprostheses]. PMID- 2890069 TI - [Cerebrospinal fluid diagnosis in intervertebral disk damage and other diseases of the central nervous system]. PMID- 2890070 TI - [Increased life expectancy of patients with transverse spinal paralysis caused by modern special treatment]. PMID- 2890071 TI - [Life expectancy and prognosis for employment after contracting tuberculosis]. PMID- 2890072 TI - [Mild hypertension. What have the extensive intervention studies accomplished?]. PMID- 2890073 TI - Disturbances of sleep and wakefulness associated with the use of antihypertensive agents. AB - Sleep disturbances are frequently associated with the use of antihypertensive drugs. They are observed mainly during the administration of drugs that affect central adrenergic mechanisms. Beta-adrenoceptor antagonists which readily penetrate into the brain (propranolol, pindolol) increase wakefulness and/or decrease REM sleep. Alpha 2-adrenoceptor agonists (clonidine, guanfacine) markedly reduce the duration of REM sleep. The catecholamine depleting agent reserpine increases REM sleep during single or repeated-dose administration, while the MAOI phenelzine shows opposite effects. The 5-HT2 antagonist ritanserin, which is chemically related to the antihypertensive agent ketanserin, increases slow wave sleep while REM sleep is decreased. Sleep disturbances have not been reported during the administration of calcium entry antagonists. However, they seem to modify the effects of hypnotics and CNS stimulants. There are no formal studies on the effects of angiotensin converting enzyme inhibitors and vasodilators on sleep in man. PMID- 2890074 TI - An investigation of tolerance to the actions of leptogenic and anorexigenic drugs in mice. AB - This study compared the effects of chronic administration of anorexigenic drugs on weight loss in mice. Tolerance to the effects of peripheral anorexigenic peptides, viz. cholecystokinin-octapeptide and bombesin, developed rapidly. Morphine, cocaine and dehydroepiandrosterone-sulfate caused weight loss and appeared similar to d-amphetamine in mechanisms of action. A high dose of fluoxetine (25 mg/kg) proved to be a potent leptogenic agent but was also associated with death in some animals. A lower dose of fluoxetine (5 mg/kg) was associated with the development of tolerance. Calcitonin, a potent anorexigenic agent, did not produce weight loss and tolerance to its anorectic effect had developed by 10 days. Animals varied widely in their individual responsiveness to a given drug. Peripheral administration of peptide YY caused weight loss. We conclude that acute or chronic effects of agents on food intake do not necessarily predict effects on body weight. However, neurotransmitters that enhance feeding centrally appear to cause weight loss when administered peripherally. PMID- 2890075 TI - Central effects of adenosine analogs on stress-induced gastric ulcer formation. AB - Rats subjected to restraint stress developed gastric lesions that could be reduced by R-phenylisopropyladenosine (R-PIA) administered intracerebroventricularly. This protective effect was reversed by 8 sulfophenyltheophylline given centrally, and by peripherally administered 8 phenyltheophylline. These results suggest that central adenosine receptors mediate the effect. In subsequent studies it was found that if the absolute level of ulcer formation in control rats was low, R-PIA had no ulcer protective effect. Thus, although it appears that adenosine receptors are important in attenuating pathological gastric responses to stress, this attenuation seems to be dependent on the level of ulcer formation in control animals. PMID- 2890076 TI - [Multi-indicator biochemical and clinical evaluation of occupational exposure of workers in the petrochemical industry. II. Results of the search for early clinico-biochemical signs of exposure to toxic substances present in the petrochemical industry. Analysis of the results of 5-year epidemiological studies]. AB - The activities of GGT (EC 2.3.2.1.) and glycine transaminidase (EC 2.6.2.1.) increased in all studied groups after at minimum four years of exposure to: acetobenzene, furfurol, ethylene--derivatives, polypropylene and butadiene. Besides these universal indicators the specific ones were found for a particular group of exposure: for acetobenzene--sialic acid, haptoglobine and IgA, for furfurol--sialic acid and haptoglobine, for ethylene--derivatives--haptoglobine, ceruloplasmine and the activity of arginase of the red blood cells, for polypropylene--IgA, for butadiene--proteolytic activity. These changes are treated as a manifestation of adaptive processes--the answer of the body to the environmental stimuli but not as the signs of early damage. The need of verification of the results by prospective studies is stressed. PMID- 2890077 TI - Molecular basis of phenylketonuria and its clinical applications. PMID- 2890078 TI - Hepatic response to insulin in control of glucose kinetics in the neonatal lamb. AB - Imprecise control of neonatal glucose homeostasis may be partially due to decreased hepatic response to insulin. In prior kinetic studies the effect of that response could not be determined because the hormonal effects of insulin could not be separated from those of glucagon. Somatostatin (SRIF) suppresses secretion of both and has been used to differentiate the hormonal effects. Eighteen term lambs (age 4.2 +/- 0.3 days and birth weight 4.0 +/- 0.2 kg (M +/- SEM] were infused with 0.9% NaCl at 0.06 mL.kg-1 min-1 plus 100 microCi/kg D[6 3H] glucose by prime plus constant infusion. Ra (production) and Rd (utilization) were measured during infusion of SRIF or SRIF plus replacement insulin (0.2 mU.kg 1 min-1). There was a rise in pl. glucose (98 +/- 10 to 119 +/- 10 mg/dL (P less than .0001)); a fall (46.2%) in pl insulin [13 +/- 2 to 7 +/- 1 microU/mL (P less than .0004); a rise in Ra (7.8 +/- 1.5 to 13.2 +/- 4.1 mg.kg-1 min-1 P less than .047); and a rise in Rd (7.7 +/- 1.4 to 11.3 +/- 3.0 mg.kg-1 min-1 (P less than .047)) in SRIF treated animals compared to nontreated controls. There was no change in plasma glucagon (454 +/- 182 to 255 +/- 141 pg/mL) in SRIF treated animals compared to nontreated controls. All perturbations were eliminated when SRIF plus replacement insulin produced control insulin levels. Insulin suppression in the neonatal period resulted in glucagon being unopposed which produced an elevated rate of glucose production and elevated plasma glucose concentration. PMID- 2890079 TI - Hypophysectomy does not alter the effects of somatostatin or growth hormone on canine splanchnic biogenic amine release. AB - We have demonstrated previously that growth hormone (GH) and somatostatin (somatotropin release inhibitory factor, SRIF) exert comparable effects on the release of splanchnic biogenic amines. The purpose of the present investigation was to study further the response of the two hormones and see whether the similarity persists in dogs completely deprived of endogenous GH. Experiments were conducted in seven hypophysectomized dogs fitted with an indwelling portal catheter. Two to 4 weeks after surgery the responsiveness of their catecholaminergic neurons was tested by an injection of human beta-endorphin (20 micrograms/kg); it caused a rise in portal catecholamine levels equivalent to that seen in intact dogs. Then the effect of a spike concentration of SRIF or GH on hepatic portal and peripheral levels of free serotonin and catecholamines was studied, all by radioenzymatic methods. The intravenous injection of ovine GH (100 micrograms/kg) or equimolar amounts of SRIF (7.5 micrograms/kg) produced in the hepatic portal circulation a transient but statistically significant rise of serotonin and a concomitant reduction in the concentration of dopamine, norepinephrine, and epinephrine. No changes were found in the peripheral circulation. The response patterns to SRIF or GH were virtually identical, which is in keeping with our other data, suggesting that the effect of GH on splanchnic biogenic amine secretion is SRIF-dependent and mediated by SRIF-containing neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890080 TI - Cloning and expression of 130-kd mosquito-larvicidal delta-endotoxin gene of Bacillus thuringiensis var. Israelensis in Escherichia coli. AB - Five recombinant E. coli clones exhibiting toxicity to Aedes aegypti larvae were obtained from a library of 800 clones containing XbaI DNA fragments of 110 kb plasmid from B. thuringiensis var. israelensis. All the five clones (pMU 14/258/303/388/679) had the same 3.8-kb insert and encoded a major protein of 130 kDa which was highly toxic to A. aegypti larvae. Three clones (pMU 258/303/388) transcribed the 130 kD a gene in the same direction as that of lac Z promoter of pUC12 vector whereas the transcription of the other two (pMU 14/679) was in the opposite direction. A 1.9-kb fragment of the 3.8 kb insert coded for a protein of 65 kDa. Partial DNA sequence of the 3.8 kb insert, corresponding to the 5' terminal of the 130 kDa gene, revealed a continuous reading frame, a Shine Dalgarno sequence and a tentative 5'-regulatory region. These results demonstrated that the 3.8 kb insert is a minimal DNA fragment containing a regulatory region plus the coding sequence of the 130 kDa protein that is highly toxic to mosquito larvae. PMID- 2890081 TI - Three fim genes required for the regulation of length and mediation of adhesion of Escherichia coli type 1 fimbriae. AB - Three novel fim genes of Escherichia coli, fimF, fimG and fimH, were characterized. These genes were not necessary for the production of fimbriae but were shown to be involved in the adhesive property and longitudinal regulation of these structures. Complementation experiments indicated that both the major fimbrial subunit gene, fimA, and the fimH gene in combination with either the fimF or the fimG gene were required for mannose-specific adhesion. The fimF, fimG and fimH gene products were likewise shown to play a major role in the fimbrial morphology as longitudinal modulators. The amount of FimF, FimG and FimH proteins appeared to control the length and number of the fimbriae. The DNA sequence of a 2050 bp region containing the three genes was determined. The corresponding protein sequences all exhibited homology with the fimbrial subunit protein, FimA. PMID- 2890082 TI - Expression of the larvicidal gene of Bacillus sphaericus 1593M in the cyanobacterium Anacystis nidulans R2. AB - A 3.6 kb HindIII DNA fragment from Bacillus sphaericus 1593M was cloned and expressed in Escherichia coli and B. subtilis using pHV33 as shuttle vector and in the cyanobacterium Anacystis nidulans R2 with pUC303 as shuttle vector. The level of toxin activity of the respective recombinant plasmids pGsp04 and pGsp12 against Culex mosquito larvae was found to be the same in Escherichia coli and in the cyanobacterium. PMID- 2890083 TI - Purification and characteristics of glucocorticoid antagonizing factor in endotoxemia. AB - The present study involved the purification of GAF (glucocorticoid antagonizing factor) released in blood of endotoxemic mice, using the inhibition rate of tryptophan oxygenase (TO) activity in the mice liver as a parameter, to determine if this plays a role in metabolic disorders. GAF-rich serum in zymosan-primed and endotoxin-injected mice was subjected to chromatography on DEAE-Sepharose CL-6B, Blue Sepharose CL-6B and Sephadex G-200 superfine columns. Finally, GAF fractions were purified by chromatography on a DEAE-Sepharose CL-6B column. The purified GAF showed a single band in electrophoresis in sodium dodecyl sulfate (SDS) polyacrylamide gel. The molecular weight of GAF was estimated to be 90,000. The purified GAF was regarded as glycoprotein. No factor (100 micrograms) exhibited lethal action on mice. The activity of TO in cortisone treated mice after injection of purified GAF was markedly lower than that in cortisone alone treated mice. On the other hand, there were no differences in tyrosine aminotransferase activities between the GAF plus cortisone injected group and cortisone only treated group. The glucose level after injection of GAF in cortisone treated mice initially showed hyperglycemia, but declined toward hypoglycemia 2 hr after injection, and thereafter returned nearly to the normal range by 4 hr. The liver glycogen level in GAF plus cortisone-treated mice was markedly lower than that in cortisone-alone treated mice. PMID- 2890084 TI - Increase in intradermal vascular permeability caused by pertussis toxin from Bordetella pertussis. AB - Rabbits that were injected intradermally with pertussis toxin (PT), produced from Bordetella pertussis, showed slight edema and erythema at the injection sites, but not hemorrhage nor necrosis. The edema lesions were stained blue by the intravenous injection of Pontamine Sky Blue 6B dye, suggesting that PT caused increased vascular permeability, similarly to the permeability factor (PF) of cholera toxin. The reaction of the PF of PT could be determined by measuring the diameter of the blue area. The diameter of the blue area bore a good linear relationship to the logarithm of the dose of PT. The activity of the PF was neutralized by anti-PT rabbit serum. Detoxification of PT with formalin did not increase the vascular permeability, but reverted pertussis toxoid showed a PF reaction in proportion to the reverted leukocytosis-promoting and histamine sensitizing activities of PT. The supernate of a Bordetella pertussis culture also induced a PF reaction and the reaction could be made clear by heating the supernate at 56 C for 30 min, but the supernate of Bordetella bronchiseptica did not induce the reaction at all. PMID- 2890085 TI - Maintenance therapies in schizophrenia. PMID- 2890086 TI - Haemorrhagic fever with renal syndrome involving the liver. AB - A case of haemorrhagic fever with renal syndrome that originated in Malaysia is reported. The patient presented with clinical symptoms which were not typical of the disease as seen in endemic regions. Renal involvement, which is characteristic of haemorrhagic fever with renal syndrome, was mild, and the predominant symptom was a persistently marked elevation of serum transaminase levels that was suggestive of hepatitis. Liver involvement has not been described in the Asian form of haemorrhagic fever with renal syndrome. The patient developed a petechial skin rash and had severe thrombocytopenia. Serological confirmation of the diagnosis of haemorrhagic fever with renal syndrome was obtained by the demonstration of significant antibody rises to hantaviruses in the patient's acute- and convalescent-phase sera. PMID- 2890087 TI - Experiments with the nematocysts of Carybdea rastoni ("Jimble") PMID- 2890088 TI - Choice of antihistamines for allergic rhinitis. PMID- 2890089 TI - [The clinical picture of benzodiazepine and alcohol poisoning]. PMID- 2890090 TI - [Immuno-histochemical study of medullary thyroid carcinoma]. AB - Five peptide hormones including calcitonin (CT) and gastrin-releasing peptide (GRP), serotonin (5HT), CEA, nervous tissue specific proteins and monoclonal antibody Leu-7 were immuno-histochemically studied on 60 cases of medullary thyroid carcinoma (MTC). In addition, localization of varied products in the tumor cells and its relations with the clinical features in some cases were evaluated. MTC contains a variety of products in many cases, and CT and CEA were positive in all cases. In 50 of the 57 cases (87.7%), GRP was positive, which suggested that GRP could be a novel tumor marker for this tumor. Furthermore, in tumor cells and C-cell hyperplastic foci, identical cells were sometimes revealed to possess both CT and GRP. Existence of somatostatin (SS), substance-P (SP), beta-MSH, 5 HT, Leu-7 and NSE in the tumor cells were confirmed. NSE was positive in 32 of the 47 cases (61.8%) which could confirm that MTC possesses neuroendocrine nature. In two cases of autopsy in which the tumors were highly malignant in clinical course and undifferentiated in histology, most tumor cells showed poor stainability for peptide hormones, suggesting that specific qualities as neuroendocrine tumor had been lost. In familial cases, the tumor tended to contain multiple substances. PMID- 2890091 TI - Cholinergic function and alpha-bungarotoxin binding in PC12 cells. AB - The cell line PC12, derived from an adrenal chromaffin cell tumor, expresses both ganglionic (C6) acetylcholine receptors (nAChR) and an alpha-bungarotoxin (BGT) binding protein of unknown function. We measured nicotinic Na+ fluxes of 180-260 nmol/mg protein X min and 0.35-0.8 pmol [125I]BGT binding sites/mg protein; 45 65% of the [125I]BGT binding was to intracellular sites. We blocked ganglionic Na+ fluxes with reversible and irreversible inhibitors and tested whether a residual BGT-sensitive flux could be identified. No such flux was detected. These experiments place an upper limit on the amount of an undetected Na+ flux such that we question whether the BGT binding protein could act as a functional nAChR X Na+ flux and [125I]BGT binding were irreversibly inactivated by the affinity directed antagonist 4-(N-maleimido)benzyltrimethylammonium bromide (MBTA), and the appearance of new nAChRs and BGT binding proteins was monitored. New ganglionic nAChRs appeared at a rate of 0.029 hr-1, corresponding to a steady state turnover t1/2 of 24 hr. BGT binding protein was synthesized more rapidly (K = 0.11 hr-1, t1/2 = 6.5 hr). When protein synthesis was simultaneously blocked with cycloheximide, insertion of BGT binding protein into the plasma membrane decreased to 11% of control values. Cycloheximide also induced a biphasic decline in intracellular BGT binding sites. Incubation of PC12 cells in 5 mM carbamylcholine for varying intervals resulted in a rapid 30% loss of Na+ flux activity. In contrast, the concentration of BGT binding protein did not change. PMID- 2890092 TI - Dual action of excitatory amino acids on the metabolism of inositol phosphates in striatal neurons. AB - Glutamate is able to stimulate inositol phosphate (IP) formation in striatal neurons in primary culture, mainly via an excitatory amino acid receptor of the quisqualate subtype. In the present study we show that carbachol (Carb)-(a cholinergic agonist), but not neurotensin or norepinephrine-induced IP production could be reduced by 40% when measured in the presence of Glu. The inhibition of the Carb response by Glu was dose dependent and reproduced by N-methyl-D aspartate (NMDA). Quisqualate elicited an additive response with Carb. 2-Amino-5 phosphonovalerate (APV) completely reversed the NMDA-induced inhibition. APV had no significant effect on Glu- or kainate-induced inhibition. Therefore, striatal neurons contain at least three different excitatory amino acid receptors: a quisqualate receptor triggering the stimulation of IP metabolism, and an NMDA and a kainate receptor, both able to decrease the Carb-induced IP formation. PMID- 2890093 TI - Inhibition of platelet aggregation by carbon monoxide is mediated by activation of guanylate cyclase. AB - Carbon monoxide (CO) inhibits human platelet aggregation triggered with threshold levels of agonists like arachidonate, ADP, collagen, thrombin, or the prostaglandin endoperoxide analogue U46619. This inhibition is counteracted by illumination with light above 400 nm indicating the involvement of a ferrous hemoprotein. An earlier suggestion that the mechanism of CO inhibition involves the cytochrome P450 protein thromboxane A2 synthase was ruled out as well as the involvement of the iron containing enzymes like cyclooxygenase or 12 lipoxygenase. In the presence of CO, no arachidonate was released from phospholipids, no increase of intracellular calcium levels was observed, and phospholipase C was not activated suggesting that the transducing mechanisms from the receptors to phospholipase C was effected in the presence of CO. cAMP levels were also unchanged but cGMP levels showed an increase of about 30%. By comparison with the guanylate cyclase stimulator nitroprusside, it was shown that such levels could block aggregation. In a 10,000 X g supernatant, CO enhanced guanylate cyclase activity 4-fold, supporting the view that CO acts by increasing platelet cGMP levels. With respect to the mechanism of guanylate cyclase action, the binding of CO to the regulatory subunit of guanylate cyclase must be responsible for the observed activation. It is concluded that cGMP is an important feedback regulator of the Pl response and that already a 25% increase in its steady state levels can cause inhibition of platelet aggregation. PMID- 2890094 TI - Heterogeneity of alpha 1-adrenergic receptors revealed by chlorethylclonidine. AB - Chlorethylclonidine (CEC) has previously been shown to inactivate only a subpopulation of the alpha 1-adrenergic receptor binding sites in rat brain. We compared alpha 1-adrenergic receptors in different tissues to determine whether such selective inactivation might reveal the presence of distinct receptor subtypes. Pretreatment of broken cell preparations with 10 microM CEC for 10 min caused a 70-80% decrease in the density of specific 125IBE 2254 binding sites in rat liver and spleen, a 25% decrease in neocortex, but no significant loss in kidney, hippocampus, heart, vas deferens, or caudal artery. The effect of CEC in liver was not reversed by extensive washing, suggesting irreversible inactivation. The selectivity between different tissues was due to differences in the efficacy of CEC inactivating the binding sites and not due to differences in binding affinity. To determine whether the effects on 125IBE 2254 binding reflected selective inactivation of functional receptors, contractile responses of rat spleen and vas deferens were examined. Pretreatment of intact tissues with 100 microM CEC for 30 min caused a large decrease in the potency and maximal contraction to norepinephrine in spleen but had no effect in vas deferens. Inhibition of specific 125IBE 2254 binding by various agonists and antagonists was determined in CEC-sensitive (liver, spleen) and insensitive (hippocampus, vas deferens) tissues. Although many drugs had similar affinities in all tissues, others were substantially less potent in the CEC-sensitive tissues. These experiments suggest that there are at least two subtypes of alpha 1-adrenergic receptors with different pharmacological properties in mammalian tissues, only one of which is inactivated by CEC. PMID- 2890095 TI - Antiproliferative and cytotoxic effects of newly discovered halogenated coral prostanoids from the Japanese stolonifer Clavularia viridis on human myeloid leukemia cells in culture. AB - The antiproliferative and cytotoxic activities of newly discovered halogenated coral prostanoids (chlorovulone, bromovulone, and iodovulone) from the Japanese stolonifer Clavularia viridis and their related compounds were determined in HL 60 cells in culture. The order of antiproliferative and cytotoxic activities of naturally occurring marine prostanoids against HL-60 cells was chlorovulone I greater than bromovulone I = iodovulone I greater than clavulone I or II greater than prostaglandin A2. The IC50 (concentrations required to inhibit cell growth by 50%) value (0.03 microM (0.01 microgram/ml)) and cytotoxic effects (greater than 0.3 microM (0.1 microgram/ml)) of chlorovulone I were about 200 and 100 times stronger than those of prostaglandin A2, respectively, on the molar basis. From our data on the structure-activity relationship of the halogenated coral prostanoids and the related compounds, we elucidated that 1) the alkylidencyclopentenone structure in these prostanoids was essential for the antiproliferative and cytotoxic activities against HL-60 cells and the introduction of halogen function at C-10 position in the structure enhanced the activities (C1 = F greater than Br = I greater than H); 2) the stereospecificity of the 12-hydroxyl group in the chlorovulone molecule was not required for the activities; 3) the presence of dienone (C5-6 and C7-8) in the structure potentiated the activities. Bivariate DNA/bromodeoxyuridine analysis with a flow cytometer showed that chlorovulone I transiently arrested the cell cycle progression from G1 to S after 24-hr exposure to the nontoxic concentrations (0.03 and 0.09 microM) and caused the lasting blockade of leukemia cells in G1 at the cytotoxic concentration. These results suggest that these coral prostanoids and related compounds may be a promising antileukemic agent. PMID- 2890096 TI - Regulation of troponin C synthesis in primary culture of chicken cardiac muscle cells. AB - Cardiac myocyte cell culture from fourteen day old embryonic chicken heart was prepared. This cultured cell system was used to examine the regulation of troponin C (TnC) synthesis in cardiac muscle. To examine the regulation of TnC polypeptide synthesis, cardiac myocyte cells were pulse labelled with 35S methionine at different days after plating. The synthesis of TnC was measured by determining the amount of radioactivity incorporated into the TnC polypeptide following separation by two dimensional gel electrophoresis. These measurements showed that TnC synthesis was maximum in 36 to 48 h old cultures and reached its lowest level in 4 day old cultures. This was in contrast to the synthesis of actin and tropomyosin. Synthesis of these polypeptides were lowest in 36 to 48 h old cultures and was maximum in 7 day old cultures. To examine whether the synthesis of TnC polypeptide paralleled the levels of TnC mRNA the sequences homologous to quail slow TnC cDNA clone were measured by hybridisation. The results showed that the decrease in the synthesis of troponin C polypeptide cannot be fully explained by the decrease in the steady state level of troponin C mRNA. The possibility of a role of translational control of troponin C mRNA in this process is discussed. PMID- 2890097 TI - Isolation of telomere DNA from Neurospora crassa. AB - The most distal known gene on Neurospora crassa linkage group VR, his-6, was cloned. A genomic walk resulted in isolation of the telomere at VR. It was obtained from a library in which the endmost nucleotides of the chromosome had not been removed by nuclease treatment before being cloned, and mapping indicates that the entire chromosome end has probably been cloned. Sequences homologous to the terminal 2.5 kilobases of DNA from VR from these Oak Ridge N. crassa strains are found at other sites in the genome. To characterize these sites, I crossed an Oak Ridge-derived his-6 strain with a wild-type strain of different genetic background (Mauriceville) and characterized the hybridization patterns seen in the progeny. It appears that the sequences homologous to the VR terminus are found at genetically different sites in the two parental strains, and no hybridization to the VR telomere from Mauriceville was detected. The other genomic copies identified in the Oak Ridge parent were not telomeres. I suggest that any repeating sequence blocks found immediately adjacent to the VR terminus in Oak Ridge strains must be small and that the repeating element identified in that background may be an N. crassa transposable element integrated near the the chromosome end at VR. PMID- 2890098 TI - Amplification of the IMP dehydrogenase gene in Chinese hamster cells resistant to mycophenolic acid. AB - The regulation of IMP dehydrogenase (IMPDH) was analyzed in Chinese hamster V79 cell variants that exhibit different degrees of resistance to the cytotoxic effect of mycophenolic acid, a specific inhibitor of IMPDH. Western blot (immunoblot) analysis with an IMPDH antiserum revealed a 14- to 27-fold increase in the amount of enzyme in the mycophenolic acid-resistant cells. The antiserum was also used to screen for a phage containing the IMPDH cDNA sequence from a lambda gt11 expression library. Northern blot (RNA blot) analyses of total cellular and poly(A)+ RNA showed that an IMPDH cDNA probe hybridized to a 2.2 kilobase transcript, the amount of which was associated with increased resistance. Southern blotting with the probe indicated an amplification of the IMPDH gene in the mycophenolic acid-resistant cells. Our findings suggest that the acquired mycophenolic acid resistance of the V79 cell variants is associated with increases in the amount and activity of IMPDH and the number of IMPDH gene copies. PMID- 2890100 TI - The effects of benzodiazepines upon the fidelity of mitotic cell division in cultured Chinese hamster cells. AB - 4 benzodiazepine sedatives, namely diazepam, medazepam, midazolam and bromazepam were investigated for their effects upon the fidelity of cell division in both low passage number and immortalised Chinese hamster cell lines. The study revealed substantial differences in the effect of these structurally related drugs upon mitosis, which may reflect different mechanisms of action of the drugs in cultured cells. Diazepam and medazepam exposure of immortal and low passage number cells resulted in the formation of monopolar mitotic spindles and subsequent metaphase arrest. The production of these spindles may be explained by the inhibition or centriole separation . In contrast, midazolam and bromazepam failed to produce observable changes in spindle structure. All 4 benzodiazepines produced significant toxicity in low passage number cells whereas, immortalised cells were more resistant to their toxic effects. They all induced metaphase chromosome dislocations in immortalised cells, whereas only diazepam and medazepam produced such effects in the low passage number cell line. In general, immortal cells appeared to be less sensitive to the toxic effects of benzodiazepines than the low passage number cells. PMID- 2890099 TI - Regulated expression of the tyrosine hydroxylase gene by epidermal growth factor. AB - The addition of epidermal growth factor (EGF) to cultures of the rat PCG2 pheochromocytoma cell line increased the level of RNA coding for tyrosine hydroxylase (TH). A region of DNA containing 5'-flanking sequences of the TH gene was fused to a heterologous gene and transfected into a rat anterior pituitary cell line, GH4. The TH gene sequences from +27 to -272 contained information sufficient for the induction of TH by EGF. Two regions within this TH DNA were extensively homologous to the EGF regulatory element of the rat prolactin gene. PMID- 2890101 TI - Purification and characterization of a tyrosine aminotransferase from Crithidia fasciculata. AB - Tyrosine aminotransferase (TAT, EC 2.6.1.5) from the kinetoplastid, Crithidia fasciculata, was purified over 2000 fold to electrophoretic homogeneity. The native form of the enzyme had a molecular weight of approximately 100,000, whereas under denaturing conditions it produced two polypeptides of approximately 50,000 and 48,000, respectively. Absence of a reaction with the periodic acid Schiff stain suggested that the crithidial enzyme was not a glycoprotein. It was relatively stable and remained active over a wide range of pH and temperature. It exhibited a broad substrate specificity and was able to utilize L-tyrosine, L tryptophan, and L-phenylalanine as amino donors. Antiserum produced against partially purified crithidial tyrosine aminotransferase failed to inhibit the enzymatic activity. The same antiserum cross-reacted with a soluble extract from Trypanosoma brucei gambiense, but not with that from normal mouse liver, confirming evolutionary conservatism between the two protozoa. PMID- 2890102 TI - Synthesis of a somatostatin-like peptide by Plasmodium falciparum. AB - The intracellular parasite, Plasmodium falciparum, was found to synthesize a peptide similar to mammalian somatostatin. High performance liquid chromatography of acetic acid extracts of Plasmodium-infected erythrocytes revealed a metabolically labeled peptide that co-eluted with rat somatostatin and that was reactive with antibody against rat somatostatin. Bioassay of partially purified Plasmodium peptide demonstrated somatostatin activity. Acetic acid extracts from non-synchronized infected cultures were shown by radioimmunoassay to contain the equivalent of 150 molecules of somatostatin per parasite. Somatostatin was not detectable in erythrocytes of non-infected cultures. PMID- 2890103 TI - Specificity of a cysteine proteinase of Entamoeba histolytica towards the alpha 1 CB2 peptide of bovine collagen type I. AB - The cysteine proteinase of Entamoeba histolytica was shown to hydrolyze the cyanogen bromide peptide alpha 1-CB2 of calf skin collagen type I yielding two split products. Amino acid analyses of the formed peptides and estimation of the amino-terminal residues revealed that the alpha 1-CB2 peptide was exclusively cleaved between Gly10 and Leu11 within the sequence -Arg9-Gly10-Leu11-yielding two peptides with 7 and 29 amino acids, respectively. Under identical conditions the ratio of hydrolysis of the Gly10-Leu11 bond in the alpha 1-CB2 peptide to the Gly23-Phe24 bond within the internal sequence -Arg22-Gly23-Phe24- of bovine insulin B-chain was 100:65. The enzyme was found to split both benzyloxycarbonyl Arg-Arg-methoxy-2-naphthylamide and benzyloxycarbonyl-Arg-Gly-2-naphthylamide. The ratio of hydrolysis of these substances was 100:11.6. Benzyloxycarbonyl-Gly Arg-2-naphthylamide was a very poor substrate for the enzyme. PMID- 2890104 TI - Isolation and partial characterization of the hexokinase isoenzymes from pathogenic and non-pathogenic strains of Entamoeba histolytica. AB - Isoenzyme electrophoretic patterns (zymodemes) are increasingly used to distinguish between pathogenic and non-pathogenic strains of Entamoeba histolytica. Isolates of E. histolytica from asymptomatic and symptomatic cases have been shown to differ in the electrophoretic mobility of their hexokinase and phosphoglucomutase isoenzymes. The hexokinase isoenzymes from a non-pathogenic strain and from a pathogenic strain of E. histolytica were purified by fast protein liquid chromatography in several steps, which included a separation by size, chromatofocusing, and anion exchange chromatography. The isoenzymes differed in their isoelectric points, which ranged from pH 4.8-5.4, but had very similar kinetic properties and almost identical apparent molecular weights (48,000) in sodium dodecyl sulfate polyacrylamide gels, as well as on gel filtration columns. Comparison of tryptic peptide analysis of each of the isoenzymes indicated considerable homology between the non-pathogenic and pathogenic forms. Antibodies produced against each of the two pathogenic hexokinase isoenzymes inhibited their enzymatic activity. The antibodies also inhibited the activity of the isoenzymes of the non-pathogenic strain. Our findings suggest that the isoenzymes have structural similarities, and that the pathogenic ones differ from the non-pathogenic ones in their electromobility due to post-translational modifications. PMID- 2890105 TI - Co-release of glutamate and aspartate from cholinergic and GABAergic synaptosomes. AB - Glutamate and aspartate are known to be released in a calcium-dependent fashion by depolarizing stimulation of mammalian brain synaptosomes (isolated nerve endings), an observation which strengthens their claims to be neurotransmitter candidates. The source of these compounds has been interpreted as the exclusively glutamatergic or aspartatergic synaptosome sub-populations assumed to be present in the standard heterogeneous preparations from mammalian brain. Several neurotransmitter-specific synaptosomal surface markers have recently been identified by immunolysis studies and these have allowed separation of subpopulations of synaptosomes by an affinity purification method. These markers appear to be closely related to the biosynthetic enzyme for the principal neurotransmitter released by each sub-category of synaptosome. We have isolated highly purified, metabolically active, GABAergic and cholinergic synaptosomes from cerebral cortex using antisera recognizing either glutamate decarboxylase (GAD) or choline acetyltransferase (ChAT), in conjunction with magnetic microspheres covalently coupled to Protein A (ref. 8), and now report that these synaptosomes release both glutamate and aspartate, in addition to their principal neurotransmitter, when treated with chemical depolarizing agents. PMID- 2890106 TI - Centrifugal fibres synapse on dopaminergic interplexiform cells in the teleost retina. AB - In teleost fish, centrifugal fibres originating in the olfactory bulb and containing FMRFamide-like and luteinizing hormone releasing hormone (LHRH)-like peptides project to the retina and terminate along the border of the inner nuclear and inner plexiform layers. Using a novel simultaneous two-colour immunolabelling technique, we have found that these centrifugal fibres are often closely apposed to the dopaminergic interplexiform cells. Contacts between centrifugal fibres and dopaminergic interplexiform cells were observed by electron microscopy to be conventional type synaptic junctions. Since the dopaminergic interplexiform cells make synapses on horizontal and bipolar cells, providing an intraretinal centrifugal pathway for information flow from the inner to the outer plexiform layers, we conclude that every neuron in the teleost retina is potentially susceptible to central influences via these centrifugal fibres and dopaminergic interplexiform cells. PMID- 2890107 TI - [Agoraphobia and (or) depression?]. PMID- 2890108 TI - [The effect of antihypertensive agents on serum lipids]. PMID- 2890109 TI - [Study by Amsterdam pharmacists concerning amounts of tranquilizers and sedatives delivered to 'normal' patients and drug users]. PMID- 2890110 TI - [Current viewpoints in the pathogenesis and therapy of peptic ulcer]. PMID- 2890111 TI - [Consensus on management of the undescended testis]. PMID- 2890112 TI - Characterization of quisqualate recognition sites in rat brain tissue using DL [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and a filtration assay. AB - The binding of [3H]AMPA (DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid), a ligand for the putative quisqualate excitatory amino acid receptor subtype, was evaluated using centrifugation and filtration receptor binding techniques in rat brain crude synaptosomal membrane preparations. Maximal specific binding of [3H]AMPA occurred in Triton X-100 treated membranes in the presence of the chaotropic agent potassium thiocyanate (KSCN). The effects of KSCN on binding were reversible and optimal at 100 mM. Supernatant obtained from detergent-treated membranes inhibited specific [3H]AMPA and [3H]kainic acid binding, suggesting the presence of an inhibitory agent which was tentatively identified as glutamate. Using centrifugation, saturation analysis revealed two distinct binding sites in both the absence and presence of KSCN. The chaotrope was most effective in increasing binding at the low affinity binding site, enhancing the affinity (Kd) without a concommitant change in the total number of binding sites. Using filtration, a single binding site was detected in Triton treated membranes. Like the data obtained by centrifugation, KSCN enhanced the affinity of the receptor (Kd value = 10 nM) without altering the number of binding sites (Bmax = 1.2 pmol/mg protein). The rank order of potency of various glutamate analogs in the [3H]AMPA binding assay was quisqualate greater than AMPA greater than L-glutamate greater than kainate greater than D-glutamate, consistent with the labeling of a quisqualate-type excitatory amino acid receptor subtype. L-glutamic acid diethylester, and 2-amino-7-phosphonoheptanoic acid (AP7) were inactive. The present technique provides a rapid, reliable assay for the evaluation of quisqualate-type excitatory amino acid agonists and/or antagonists that may be used to discover more potent and selective agents. PMID- 2890113 TI - Alpha-adrenergic receptor regulation of Ca2+/Mg2+-ATPase in brain synaptic membranes. AB - The effects of alpha 1 and alpha 2-adrenergic receptor ligands on Ca2+/Mg2+ ATPase have been studied using synaptosomal plasma membranes isolated from rat brain cortex. Both phenylephrine and clonidine inhibited Ca2+/Mg2+-ATPase, in a concentration-dependent fashion. IC50 values for half-maximal inhibition for phenylephrine and clonidine were 29 microM and 18 microM, respectively. The inhibitory effect of phenylephrine was reversed by the alpha antagonist prazosin while yohimbine and rauwolscine reversed the inhibition of enzyme activity by clonidine. The two antagonist subtypes were effective only against the respective agonist subtypes, demonstrating distinct subtype preferences. Analysis of the kinetics of enzyme inhibition indicate both agonists to be noncompetitive. Some evidence suggests that yohimbine may exhibit mixed agonist/antagonist properties which depend on [Ca2+]. The present study provides biochemical evidence to support auto receptor alpha-adrenergic receptor regulation of neurotransmitter release. PMID- 2890114 TI - Altered expression of a heat shock protein in the mammalian nervous system in the presence of agents which affect microtubule stability. AB - In vitro incubation of the isolated rabbit retina at elevated temperature results in the synthesis of a heat shock protein of M.W. 74,000 (hsp74). Recently we have demonstrated that this protein is associated with preparations of purified retinal microtubules and intermediate filaments. In order to examine the possibility that hsp74 synthesis is related to cytoskeletal stability, the effects of agents known to specifically affect microtubules were examined using an in vitro retinal system. Taxol, an antimitotic agent which stabilizes microtubules, was found to reduce the level of hsp74 synthesized in response to elevated temperature. Colchicine, a potent microtubule de-stabilizing agent, did not induce hsp74 synthesis in the absence of elevated temperature, however, under heat shock conditions, hsp74 synthesis was elevated in the presence of colchicine. Kinetics of microtubule assembly were similar in preparations isolated from cerebral hemispheres of control and hyperthermic animals however, microtubules from the latter were altered in appearance and exhibited a higher degree of crosslinking. PMID- 2890115 TI - Cholinergic stimulation of inositol phosphate production in cultured anterior pituitary cells. AB - The effects of acetylcholine and of the muscarinic receptor agonist carbachol on inositol phosphate production were studied in cultured rat anterior pituitary cells. In the presence of the cholinesterase inhibitor physostigmine, acetylcholine significantly (p less than 0.05-p less than 0.01) stimulated inositol phosphate formation in a concentration-related fashion: carbachol, but not oxotremorine, produced similar effects. The increase in the amount of inositol phosphates (primarily inositol trisphosphate and inositol bisphosphate) was very rapid, an effect potently antagonized by the muscarinic receptor antagonist atropine. This agent significantly attenuated the stimulatory effect of carbachol on growth hormone (GH) release. These results indicate that the effects exerted by acetylcholine on anterior pituitary function (i.e. GH release) may be mediated, at least in part, by receptor-activated polyphosphoinositide hydrolysis. In addition, acetylcholine and carbachol's relation with other intracellular pathways and with hormone release is discussed. PMID- 2890117 TI - Emesis induced by cisplatin in the ferret as a model for the detection of anti emetic drugs. AB - The intravenous injection of cisplatin in the ferret caused a consistent emetic (vomiting/retching) response. Emesis induced by cisplatin was abolished by the 5 hydroxytryptamine (5-HT) M-receptor antagonists ICS205-930, zacopride, dazopride and metoclopramide. The neuroleptic agents haloperidol, fluphenazine, domperidone, sulpiride and tiapride also antagonized emesis induced by cisplatin but only a proportion of the animals were completely protected and diazepam and prednisolone only reduced the intensity of the response. It is concluded that compounds used in the clinic to antagonise emesis induced by chemotherapy are effective in the ferret model. Antagonism of emesis induced by cisplatin in the ferret was most potently achieved by the use of the 5-HT M-receptor antagonists ICS205-930 and zacopride. However, an antagonism of dopamine receptors would appear relevant to the anti-emetic effects of the neuroleptic agents and may contribute to the anti-emetic effects of metoclopramide. Diazepam and prednisolone exert their modest antagonism by unknown mechanisms. The use of the 5-HT M-receptor antagonists is revealed as a novel approach to the treatment of emesis induced by cisplatin. PMID- 2890118 TI - Behavioural consequences of the infusion of dopamine into the nucleus accumbens of the common marmoset (Callithrix jacchus). AB - Marmosets, shown to have comparable levels of spontaneous locomotor activity, assessed in cages equipped with infra-red photocell units, could be separated into "high", "moderate" and "low activity" responders on the basis of their locomotor hyperactivity response to peripherally administered (-)N-n propylnorapomorphine [(-)NPA]. Animals selected as "low" and "high activity" responders to (-)NPA were subjected to chronic infusion of dopamine, or its solvent, bilaterally into the nucleus accumbens for 13 days through Alzet osmotic minipumps. Both "low" and "high activity" responders exhibited an increased locomotor activity which peaked on days 6-7 of the infusion. This hyperactivity, caused by infusion of dopamine was antagonised by small doses of sulpiride and fluphenazine. After the infusion, the level of spontaneous locomotor activity of the marmosets was unchanged from pre-infusion values. However, 2-3 weeks after discontinuing the infusion, the animals initially classified as "low activity" responders showed markedly enhanced activity when challenged with (-)NPA, and conversely, animals initially classified as "high activity" responders showed a reduced responsiveness to (-)NPA. It is concluded that the consequences of a persistent increase in the activity of dopamine in the nucleus accumbens of the brain of the marmoset are to (a) enhance locomotor activity during infusion and (b) after discontinuing infusion, to modify the locomotor responsiveness to challenge with a dopamine agonist, with the direction of the change dependent on the initial basal locomotor responsiveness to (-)NPA. PMID- 2890116 TI - Modulation by enkephalin analogues and neuroleptics of apomorphine-induced stereotypy and turning behaviour in rats. AB - The aim of the present investigation was to examine which areas of the brain might mediate the anti-apomorphine action of some opioids, which were found previously to be active upon subcutaneous application. As the first step, the substances were injected intracerebroventricularly or into the nucleus accumbens, a mesolimbic region which is rich in dopamine, and the inhibition of stereotypy induced by apomorphine was quantified. In a separate group of animals (rats with unilateral lesion of the nigra) the antagonism of turning behaviour elicited by apomorphine was measured. Substances examined were morphine, a mu-selective opiate; D-Ala2,Nle5-enkephalin sulphonic acid (ES), a delta-selective opioid peptide; D-Met2,Pro5-enkephalinamide (EA), a highly potent but non-selective opioid; and two dopamine receptor blockers, haloperidol and chlorpromazine, for comparison. Examining the antagonism of turning behaviour induced by apomorphine, the order of potency was EA greater than haloperidol greater than morphine greater than ES approximately equal to chlorpromazine if injections of the substances were intracerebroventricular and EA greater than morphine much greater than haloperidol approximately equal to ES much greater than chlorpromazine when administered into the nucleus accumbens. The order of potency for the suppression of stereotypy induced by apomorphine was EA much greater than haloperidol greater than morphine greater than ES greater than chlorpromazine upon intracerebroventricular application and EA much greater than haloperidol greater than morphine ES greater than chlorpromazine if injected into the nucleus accumbens. The data indicate that endogenous opioids might inhibit the activity of dopamine in brain through the nucleus accumbens. PMID- 2890119 TI - Purification of a kappa-opioid receptor subtype from frog brain. AB - A kappa-opioid receptor subtype was purified from a digitonin solubilized preparation of frog brain membranes using affinity chromatography. The affinity resin was prepared by coupling D-Ala2-Leu5-enkephalin to Sepharose-6B matrix. After elution of the receptor by 50 mumol naloxone, the kappa-subtype was separated from the mu- and delta-subtypes by gel permeation chromatography on Sepharose-6B. The purified receptor binds 3,900 pmol [3H]-ethylketocyclazocine per mg protein (a 4,300-fold purification over the membrane-bound receptor) with a KD of 8.3 nM. The purified receptor protein exhibits high affinity for kappa selective ligands. The purified fraction shows two bands (Mr 65,000 and 58,000) in sodium dodecyl sulfate gel electrophoresis. PMID- 2890121 TI - Tank turret crush injuries of the foot. PMID- 2890120 TI - Neuronal uptake and laminar distribution of tritiated aspartate, glutamate, gamma aminobutyrate and glycine in the prestriate cortex of squirrel monkeys: correlation with levels of cytochrome oxidase activity and their uptake in area 17. AB - The neuronal uptake and laminar distribution of cortically injected tritium labeled gamma-aminobutyrate (GABA), aspartic acid, glutamate and glycine was examined in the prestriate cortex of squirrel monkeys. The intent of this investigation was not to examine the role of these amino acids as neurotransmitters, but to correlate the distribution of tritium-labeled neurons with their levels of cytochrome oxidase activity. A comparison of the number of these labeled neurons was made between the metabolically active "puff" and the less active "nonpuff" regions. In addition, these results were contrasted with the findings in area 17. With each tritiated amino acid tested, labeled neurons that had either high or low levels of cytochrome oxidase activity were present in all laminae. However, the density of labeled neurons varied between lamina for a given amino acid as well as between different amino acids. While many neurons that were cytochrome oxidase-reactive were also tritium-labeled, cytochrome oxidase activity was not a prerequisite for the sequestering of tritium label. In fact, many of the labeled neurons exhibited relatively low levels of cytochrome oxidase activity. Similar to area 17, few aspartate- or glutamate-labeled neurons were present in laminae II-III. The number of labeled neurons for both amino acids increased in laminae IV-VI, with the greatest increase observed in laminae V-VI. Gamma-aminobutyrate-labeled neurons were more prevalent in laminae I and upper II than in the other laminae, whereas in area 17, a greater proportion of the labeled neurons were found in laminae V-VI. With the exception of the uppermost laminae, where GABA-labeled neurons were more abundant, the number of glycine-labeled neurons was significantly greater throughout most laminae than with the other amino acids examined. The density of glycine-labeled neurons in lamina IV, however, was significantly less than the number observed in lamina III even though lamina III was farther away from the injection site which was at the boundary between laminae V-VI. Glycine-labeled neurons were, on average, larger than those labeled with any other amino acid. Similar to area 17, more GABA- and glycine-labeled neurons were observed within the puff regions than in nonpuff regions. No puff/nonpuff differences were observed in the distribution of leucine injected controls. Labeled neurons for each amino acid included stellate-, fusiform- and pyramidal-shaped cells, each of varying sizes. However, outside the intensely labeled injection sites, no GABA-labeled pyramidal cells were observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2890122 TI - [Effects of long-term therapy with somatostatin]. PMID- 2890123 TI - The regional distribution of somatostatin and neuropeptide Y in control and Alzheimer's disease striatum. AB - Somatostatin-like immunoreactivity (SLI) and neuropeptide Y-like immunoreactivity (NPYLI) were measured in subdissections of both normal and Alzheimer's disease (AD) striatum at 5 coronal levels. Concentrations of both neuropeptides were relatively homogeneously distributed in the coronal and anterior-posterior planes except for a trend towards increased concentrations in the tail of the caudate and the posterior putamen. The nucleus accumbens showed 2-3-fold higher concentrations of both SLI and NPYLI than the rest of the striatum. There were no significant differences between control and AD brains. The high concentrations of SLI and NPYLI in the nucleus accumbens suggest that this region may receive somatostatin-neuropeptide Y afferents and that somatostatin and neuropeptide Y may play a role in the modulation of motor activity. PMID- 2890124 TI - Colocalization of GABA and tyrosine hydroxylase immunoreactivities in the axons innervating the neurointermediate lobe of the rat pituitary: an ultrastructural immunogold study. AB - Distribution of the gamma-aminobutyric acid (GABA)ergic and dopaminergic innervations was studied in the rat neurointermediate lobe using antibodies against GABA and tyrosine hydroxylase. In light microscopy, immunoperoxidase staining revealed similar distribution patterns of the axons reacting with both antibodies. Diffusely scattered in both lobes, they were more concentrated along the marginal zone of the neural lobe. Application of a double, recto-verso, immunogold labelling method in electron microscopy revealed systematic colocalization of GABA and tyrosine hydroxylase (TH) immunoreactivities in the axons innervating the intermediate lobe; in the neural lobe, almost all GABA immunoreactive axons were also labelled for TH. Thus, GABA and dopamine, hitherto reported to occur in distinct axons, in fact colocalize in the axonal systems which innervate the pituitary neurointermediate lobe. These observations suggest possible interactions (pre- or postsynaptic) of both transmitters in the functional regulation of the intermediate and neural lobes. PMID- 2890125 TI - The toxicity of MPTP to dopamine neurons in culture is reduced at high concentrations. AB - The toxicity of MPTP to dopamine (DA) neurons was studied in dissociated cell cultures from rat embryo mesencephalon. The cultures were exposed to MPTP (from 0.1 to 200 microM) for 7 days and were analyzed by catecholamine histofluorescence after incubation with alpha-methylnorepinephrine, by tyrosine hydroxylase (T-OH) immunocytochemistry and by [3H]DA uptake. Treatment with MPTP at the lower range of concentrations (between 0.1 and 5 microM) resulted in a dose-dependent reduction of the uptake of [3H]DA, which had a maximum effect at 5 microM. Further increase in the concentration of MPTP (from 10 to 200 microM) resulted in progressive attenuation of the toxic effect. Exposure to 200 microM MPTP did not produce significant reduction in the uptake of [3H]DA. Increased survival of DA neurons at the higher concentrations of MPTP, was documented by catecholamine histofluorescence and by T-OH immunocytochemistry in cultures treated with 10 and 100 microM MPTP. MPTP was shown to be a potent inhibitor of MPP+ uptake by DA neurons in culture. In the presence of 100 or 200 microM MPTP, the uptake of MPP+ was reduced to less than 20% of control levels. Therefore, the reduction of MPTP toxicity at the high concentrations can be explained, at least in part, by the inhibition of the uptake of MPP+ (the toxic metabolite of MPTP oxidation) in the presence of high concentrations of MPTP. PMID- 2890126 TI - [Retroviruses and the development of lymphoma]. AB - Retroviruses are small, RNA-containing enveloped viruses which are widely distributed in nature. They exist in many animal species as well as in man. Exogenous virus strains are horizontally transmitted between individuals of a given species, like all other virus groups. Endogenous virus strains have managed some time during evolution to infect germ line cells like oocytes and spermatocytes and are thus transmitted vertically from parents to offspring. Several retrovirus strains possess oncogenes, i.e., acutely tumor-inducing genes. There are four human retrovirus strains so far. The initially discovered strain, HTLV-I, is accepted to be a co-factor in the development of an acute T-cell leukemia in adults. HTLV-II has repeatedly been isolated from cells of patients with hairy cell leukemia. Its etiological significance is unclear at present. HTLV-III/LAV-1, now designated HIV-1, is the causative agent of AIDS. HTLV-IV and LAV-2 are additional HIV-1 related strains and are supposed to cause AIDS as well. What is known about the pathogenicity of the human retrovirus strains will be discussed. PMID- 2890127 TI - [Effect of commercial beta blockers and their combination with artificial tears on the duration of tear film stability]. AB - The influences of 8 different beta-blockers on the tear film stability-measured on the breakup time (BUT) of normal and healthy volunteers-was compared. All beta blockers led to BUT reduction, however, the lowest influence was observed with levobunolol. The duration of this effect was compared with that of levobunolol, timolol and metipranolol. While the minor BUT alterations induced by levobunolol recovered after 30 min and were completely restored after 1 h, those of the two other beta-blockers lasted for over 2 h. The combination of timolol 0.5% with different artificial tears containing mainly polyvinyl alcohol (PVA) 1.4%, methylcellulose and polyacrylic acid initially led also to BUT reduction. The best results were obtained with PVA 1.4%. PMID- 2890128 TI - Bone and joint infections in children. AB - The current approach to the diagnosis and treatment of bone and joint infections in children is presented. Guidelines for the surgical and medical regimen of each are outlined. PMID- 2890129 TI - [Erythema chronicum migrans Lipschutz]. PMID- 2890131 TI - [New problems in the treatment of hypertension]. PMID- 2890130 TI - [Treatment of hypertension and coronary heart disease]. PMID- 2890132 TI - Pharmacological analysis of hyperventilation in arthritic rats. AB - The study examined the validity of increased minute volume of ventilation as a measurement of chronic pain in arthritic rats. The opiates morphine and R 62 818 attenuated arthritic hyperventilation, but only at doses which also reduced the ventilatory response to CO2 in normal rats. The non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin and suprofen, the corticosteroids, cortisone and dexamethasone, and the tranquillizers, haloperidol and chlordiazepoxide, were essentially ineffective except at doses that also produced anti-inflammatory and/or toxic effects. A combination of an in itself ineffective dose of R 62 818 with an ineffective dose of suprofen did attenuate arthritic hyperventilation, and the combination constituted the only pharmacological treatment that did so in the absence of anti-inflammatory, toxic or intrinsic respiratory effects. The data are consistent with the hypothesis that pain rather than acidosis mediates arthritic hyperventilation. They also suggest that combinations of an opiate with an NSAID may perhaps be effective in alleviating this pain. PMID- 2890134 TI - Genetics and mosquito control. PMID- 2890133 TI - Electrophoretic studies in mosquitoes: recent advances. PMID- 2890135 TI - Clostridium perfringens meningitis in an infant: case report and literature review. PMID- 2890136 TI - Enzymuria in neonates during treatment with gentamicin or tobramycin. PMID- 2890137 TI - Comparative two-phase clinicopharmacological trial of a new antihistaminic, EGYT 2062, setastine. AB - During the two-phase clinicopharmacological trial in humans of a new antihistaminic compound EGYT-2062, setastine developed by EGIS Pharmaceutical Company, Budapest, was tested the tolerance to the drug, its pharmacodynamic effect by i. c. histamine and acetylcholine tests, and its effect on the CNS by neuropsychiatric examination on eight healthy volunteers. The side-effects appearing during treatment were recorded. A self-controlled blind study was performed. The reference compound was clemastine. Based on the results, for prolonged use a dose of 2 mg three times/day (t.i.d.) is recommended. The antihistaminic effect of setastine almost equalled that of clemastine given in a dose of 1 mg t.i.d., while its antiacetylcholine effect exceeded it, and in view of its few psychic side-effects, might be tolerated better than clemastine. PMID- 2890138 TI - EcoRI RFLP at 19 cen-q13.2 identified by the anonymous DNA sequence pPM6.7 (D19S18). PMID- 2890139 TI - RFLP for C2/11 (D7S374), a cosmid for chromosome seven. PMID- 2890140 TI - The OTA report: a policy analysis. PMID- 2890141 TI - Central beta- and alpha-adrenolytic activities of adimolol. AB - The central adrenergic blocking activity of adimolol (ADL) was studied in rats and mice in the tests which can differentiate beta-, alpha 1-, and alpha 2 adrenolytic effects. Clenbuterol- and salbutamol-induced sedation in rats (open field test) and clenbuterol-induced hyperthermia (at high ambient temperature) were antagonized by low doses of ADL (0.1-1.0 mg/kg ip). ADL (10 mg/kg ip) attenuated the clonidine-induced aggression in mice, and its higher doses (20 and 40 mg/kg ip) depressed the hind limb flexor reflex of the spinal rat and counteracted the stimulatory action of clonidine. ADL at doses from 2.5 to 40 mg/kg ip affected neither the clonidine-induced sedation in rats and mice (locomotor activity, open field test), nor the hyperthermia (at high temperature). The hypothermia (at a room temperature of 21 degrees C) induced by clonidine was partially antagonized. The Ki values for ADL displacement of 3H dihydroalprenolol and 3H-prazosin binding in the rat cerebral cortex were 1.2 nM and 951 nM respectively. These results indicate that ADL is a potent antagonist of central beta-adrenoceptors and has a weaker alpha 1-adrenolytic action. The central alpha 2-antagonistic effect is either very weak or absent. PMID- 2890142 TI - [Mechanisms of viral leukemogenesis. II. T-cell leukemia associated with retroviruses HTLV-I and HTLV-II]. PMID- 2890143 TI - [Neuroreceptors]. PMID- 2890144 TI - Delirium tremens. Update on an old disorder. AB - A retrospective study of patients who probably had delirium tremens during hospitalization for alcohol dependency is reported. Predictors of delirium tremens were daily heavy alcohol use, a past history of delirium tremens, and a past history of alcohol withdrawal seizures. Management included general measures and specific therapy for complications. Mortality was only 4.9%, which reflects the improved management techniques now available. The use of multiple interventions proved most effective. PMID- 2890145 TI - Anaphylaxis. Why it happens and what to do about it. AB - Anaphylaxis is an often severe, potentially life-threatening symptom complex. Urticaria, airway edema, vascular collapse, asthma, abdominal pain, and diarrhea are common clinical signs. Recently recognized syndromes of anaphylaxis include reactions due to exercise, food preservatives, aspirin, steroids, dialysis, various serums, and human seminal fluid. Initial therapy is directed at maintaining an effective airway and circulatory system. Administration of aqueous epinephrine is always indicated. Other measures may include oxygen delivery by controlled flow, administration of an aerosolized beta agonist, slow infusion of aminophylline, and rapid infusion of intravenous fluid. Patients with severe acute reactions should be monitored in-hospital. PMID- 2890146 TI - Bronchial asthma. Mechanisms and management of a complex obstructive airway disease. AB - Airway hyperreactivity to physical, chemical, and pharmacologic stimuli is a hallmark of bronchial asthma. In patients with extrinsic (allergic) asthma, in whom an immunologic mechanism of the IgE type can be demonstrated, specific sensitivity develops to a variety of common environmental substances, including pollen, fungus spores, house dust mites, and animal danders. Persons with intrinsic asthma, in whom immunologic mechanisms are hard to demonstrate, often have chronic sinus disease and nasal polyps and manifest clinical intolerance to nonsteroidal antiinflammatory agents. Evaluation of asthma includes a history and complete physical examination, skin tests, radioallergosorbent tests, pulmonary function tests, blood gas determination, and inhalation challenge tests. Treatment is focused on environmental control, pharmacotherapy, and immunotherapy. PMID- 2890147 TI - Duodenal ulcer. Who should have long-term maintenance therapy? AB - Duodenal ulcer frequently recurs in some high-risk patients, particularly those who smoke. Maintenance therapy with H2-receptor antagonists or sucralfate reduces the recurrence rate and appears to be safe over a one-year period. Not all patients with healed duodenal ulcer are candidates for maintenance therapy, however, and selection should be based on evaluation of such risk factors as smoking habits, previous recurrence, and history of complications. Intermittent treatment of acute episodes may be an alternative. PMID- 2890148 TI - Pharmacological control of human gastric acid secretion. PMID- 2890149 TI - Famotidine pharmacokinetics following oral and intravenous administration in patients with liver disease: results of a preliminary study. AB - The pharmacokinetics of famotidine were studied following single oral and intravenous 20-mg dose administration and after multiple oral 40-mg doses in 11 patients with alcohol-related cirrhosis of varying severity and in five healthy control subjects. No significant differences were observed, following single intravenous administration, in mean plasma famotidine half-lives or in mean plasma famotidine clearance values between the cirrhotic and control groups. Equally, values for mean maximum plasma famotidine concentrations and for mean times to peak plasma concentrations, estimated following single oral administration, were comparable between the groups. The mean (+/- s.d.) systemic availability of the drug, estimated from the areas under the curves, was 36 +/- 24% in the control subjects and 46 +/- 24% in the patients with cirrhosis. No significant increases were observed in trough plasma famotidine concentrations following multiple oral doses in the patients with cirrhosis and there was no evidence of drug accumulation. No significant changes were observed in psychometric performance in any of the patients or control subjects during the multiple-oral-dose study. Thus no significant changes occur in famotidine disposition in patients with cirrhosis even when their disease is decompensated. No reduction in drug dosage should therefore be necessary in these patients. Famotidine may produce less neurological side effects in patients with liver disease than the histamine H2-receptor antagonists used currently. PMID- 2890150 TI - Effect of oral famotidine on 24-hour intragastric acidity. AB - Twenty-four hour intragastric acidity was measured in nine volunteer subjects in a single-blind placebo-controlled cross-over study comparing the effects of famotidine with ranitidine. The volunteer subjects received famotidine (40 mg at night), famotidine (20 mg at night), ranitidine (300 mg at night) or placebo in a predetermined random order. Twenty-four hour intragastric acidity was measured after the seventh dose of each drug or placebo. Famotidine (20 mg), famotidine (40 mg) and ranitidine, all caused a significant decrease of intragastric nocturnal acidity when compared with placebo (P less than 0.01), with no effect during the daytime (P greater than 0.05). Treatment with all the drugs caused a significant rise of fasting plasma gastrin concentration compared with placebo (P less than 0.05). PMID- 2890151 TI - Drug treatment for haematemesis and melaena. AB - Searches for useful medical treatments for upper gastrointestinal bleeding have generally ignored the need for very large case numbers if useful effects are to be detected. Available results are compatible with clinically valuable treatment effects, which can only be detected if present in very large studies. PMID- 2890152 TI - Hypersensitivity reactions to drugs in acquired immunodeficiency syndrome. AB - We describe a patient with AIDS in whom recurrent drug eruption and fever following administration of various unrelated agents developed. Previous drug exposure was uneventful. A possible mechanism for this phenomenon is described. PMID- 2890153 TI - Salmonella intracerebral and subdural abscess--report of two cases. AB - Two cases of the rarely encountered Salmonella typhi subdural empyema are reported. The first was in an 11 month old infant and the second in a 25 year old adult. Neither of them suffered from typhoid fever. The causative organism was not suspected until the culture report was obtained. Both patients responded satisfactorily to therapy. PMID- 2890154 TI - Treatment with neuroleptic drugs. PMID- 2890155 TI - The benzodiazepines as substances of abuse. PMID- 2890156 TI - A new device to measure drug-induced changes on reactive and coordinative skills of human performance. AB - A computerized device for simultaneous measurement of coordinative and reactive skills related to driving was developed and tested in two consecutive trials of psychoactive agents in healthy volunteers. The test system comprises a vehicle, a driving computer (Sinclair QL), and the programming and measurement computer (IBM PC). The computerized driving programme projects to the colour--TV screen a winding road, and the driver has to keep the car on the road by turning the steering wheel. The driving proceedes at a fixed, fairly rapid rate for 5 min., and the numbers of tracking errors (deviations from the road) as well as the tracking percentage (relative length of the track driven off the road) were computed separately for both halves of the track. During the latter half of the track 60 visual or/and sound stimuli were given in random order, and the driver had to respond or not respond to them by pressing a button or by pushing a foot pedal. The number of reaction errors and the cumulative reaction time were recorded. The programme also provides a histogramme that relates the number of deviations from the road to their duration, enabling a visual judgement of the severity of errors. Matched versions (mirror image, reverse direction) of tracks of varying severity were offered to reduce learning effect during the trial. When testing the device in two placebo-controlled double-blind and cross-over trials, a considerable practice effect on tracking and reaction strategies took place, but after proper training the baselines remained reasonably stable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890157 TI - Dose-response effect of somatostatin-14 on human basal pancreatic hormones. AB - The effect of increased doses of Somatostatin-14 (3, 10, 30, 100, 300 micrograms/h) on basal release of insulin, pancreatic glucagon and pancreatic polypeptide (PP) was investigated on eight normal volunteers. Levels of Somatostatin-like immunoreactivity (SLI) was determined in order to correlate the increased SLI levels with the degree of islet hormone inhibition (r = 0.9947, p less than 0.01). By increasing the basal levels of SLI by one-third, a significant inhibition (p less than 0.01) of insulin, glucagon, and PP was noted (78.5, 78.6, 75.2%, respectively, on basal levels). The maximal effect was obtained with 300 micrograms/h for insulin, with 30 micrograms/h for glucagon and 100 micrograms/h for PP. In evaluating the relative inhibitory potency of somatostatin, expressed as ED50, the theoretic potency of somatostatin on each peptide had similar values, ranging from 30 to 10 micrograms/h. The present data show that a minimal peripheric increase in SLI is able to regulate basal islet pancreatic hormones. PMID- 2890158 TI - Reconstitution of the lysosomal proton pump. AB - Lysosomal membrane proteins solubilized with octyl beta-D-glucopyranoside were reconstituted into proteoliposomes using acetone/ether-washed phospholipids from Escherichia coli. Assays of the quenching of acridine orange fluorescence showed that addition of both ATP and valinomycin to K+-loaded proteoliposomes led to the formation of a pH gradient that was acidic inside. ATP-driven acidification took place in the absence of permeant anions and was inhibited by the "protonophore", carbonylcyanide p-trifluoromethoxyphenylhydrazone, indicating that only H+ was transported actively. Proton translocation was readily blocked by N ethylmaleimide (10 microM gave 50% inhibition of fluorescence quenching) but was unaffected by oligomycin (50 nM), orthovanadate (50 microM), or ouabain (0.5 mM); similarly, only N-ethylmaleimide affected ATP hydrolysis by proteoliposomes (88% inhibition). Other work showed that reconstitution of ATP-driven proton translocation required the presence of glycerol during protein solubilization and that optimal recovery depended on the use of both glycerol and phospholipid at this stage. We conclude that acidification of the lysosome is mediated by an ATPase capable of electrogenic H+ translocation without molecular coupling to other ionic species. PMID- 2890159 TI - Sequence of an intestinal cDNA encoding human gastric inhibitory polypeptide precursor. AB - Gastric inhibitory polypeptide (GIP) is a 42-amino acid hormone that stimulates insulin secretion in the presence of glucose. Complementary DNA clones encoding human GIP were isolated from a library prepared with RNA from duodenum. The predicted amino acid sequence indicates that GIP is derived by proteolytic processing of a 153-residue precursor, preproGIP. The GIP moiety is flanked by polypeptide segments of 51 and 60 amino acids at its NH2 and COOH termini, respectively. The former includes a signal peptide of about 21 residues and an NH2-terminal propeptide of 30 amino acids. GIP is released from the precursor by processing at single arginine residues. There is a region of nine amino acids in the COOH-terminal propeptide of the GIP precursor that has partial homology with a portion of chromogranin A as well as pancreastatin. PMID- 2890160 TI - Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells. AB - The HER2 gene encodes a cell-surface glycoprotein with extensive homology to the epidermal growth factor receptor. Recently it was found to be amplified in about 30% of primary human breast malignancies. In experiments designed to assess the role of the HER2 gene in oncogenesis, we found that overexpression of unaltered HER2 coding sequences in NIH 3T3 cells resulted in cellular transformation and tumorigenesis. PMID- 2890161 TI - Constitutive overexpression of a growth-regulated gene in transformed Chinese hamster and human cells. AB - Comparison by subtractive hybridization of mRNAs revealed a moderately abundant message in highly tumorigenic CHEF/16 cells present at very low levels in closely related nontumorigenic CHEF/18 cells. After cloning and sequencing the corresponding cDNA, computer comparison showed closest homology with the human connective tissue-activating peptide III (CTAP III). The human tumor cell cDNA hybridizing with the Chinese hamster clone was isolated, sequenced, and found to have closer similarity to the Chinese hamster gene than to CTAP III. Thus, the cloned cDNAs from Chinese hamster and human cells represent a different gene, named gro. Studies of its transcriptional regulation have shown that expression is tightly regulated by growth status in normal Chinese hamster and human cells and relaxed in the tumorigenic cells so far examined. PMID- 2890162 TI - Pancreastatin and islet hormone release. AB - The effect of pancreastatin on the release of insulin, glucagon, and somatostatin was studied in the isolated perfused rat pancreas. After an initial equilibration period (-20 to 0 min) with a basal glucose concentration (3.3 mM), the pancreata were perfused with either 16.7 mM glucose (0-40 min) or with 20 mM arginine (0-20 min). Pancreastatin was introduced 10 min prior to and throughout the administration of the high glucose and arginine and continued during their perfusion. As expected, the glucose and the arginine augmented insulin and somatostatin release. Pancreastatin (1 and 10 nM) markedly suppressed the first phase of insulin release with both insulinogogues used, while the early somatostatin secretion was not significantly decreased. However, the peak incremental somatostatin response to arginine was reduced by 50% (P less than 0.05). Conversely, the peptide (10 nM) tended to augment arginine-induced glucagon release. Pancreastatin (100 nM) also suppressed glucose-stimulated insulin release from isolated rat islets. These pancreastatin-mediated alterations in islet hormone release are reminiscent of those known to characterize non-insulin-dependent diabetes. Therefore, the significance of pancreastatin in islet physiology and pathophysiology deserves special consideration. PMID- 2890163 TI - Reduced expression of multiple forms of the alpha subunit of the stimulatory GTP binding protein in pseudohypoparathyroidism type Ia. AB - We examined the expression of the alpha subunit of the stimulatory GTP-binding protein (Gs) in fibroblasts of subjects with pseudohypoparathyroidism (PHP) type Ia by transfer blot hybridization and S1 nuclease analyses. Six subjects with PHP type Ia showed decreased steady-state content of Gs alpha mRNA. S1 nuclease analysis indicates that both long and short forms of Gs alpha mRNA are decreased, with no apparent change in the ratio of long to short forms in PHP compared with normal individuals. It appears likely that in some cases of PHP type Ia the genetic lesion affects the maintenance of mRNA levels for all forms of the Gs alpha subunit. PMID- 2890165 TI - Dopaminergic neurons from embryonic mouse mesencephalon are enriched in culture through immunoreaction with monoclonal antibody to neural specific protein 4 and flow cytometry. AB - Dopaminergic neurons represent a rare neurotransmitter phenotype within the mammalian central nervous system. The mesencephalic dopaminergic neurons form the ascending dopaminergic pathways in mammals and are involved in motor and limbic functions. Here we report that about 30% of all developing mouse mesencephalic cells, including virtually all of the dopaminergic phenotype, express surface membrane determinant(s) recognized by a monoclonal antibody to neural specific protein 4 (NSP4). We have been able to isolate and culture neurons from the mesencephalon according to their expression of NSP4, using the anti-NSP4 immunoreaction in conjunction with fluorescence-activated cell sorting. Cultures of NSP4+-sorted cells showed a significant enrichment in three morphologically distinct putative dopaminergic phenotypes when compared to unsorted mesencephalic cultures, whereas the cultures of NSP4--sorted cells were virtually devoid of dopaminergic neurons. This flow cytometric enrichment in dopaminergic neurons should provide the necessary cells for multidisciplinary study of dopaminergic phenotype differentiation. PMID- 2890164 TI - Somatostatin analogs as adjuncts to agonists of luteinizing hormone-releasing hormone in the treatment of experimental prostate cancer. AB - The combination of a long-acting delivery system for the agonist [D Trp6]luteinizing hormone-releasing hormone ([D-Trp6]LH-RH) with modern somatostatin analogs was studied in the Dunning R-3327H rat prostate cancer model. Microcapsules of [D-Trp6]LH-RH releasing 25 micrograms/day were injected once a month. In the first experiment the adjunct was the somatostatin analog D Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), administered at a dose of 2.5 micrograms twice a day, and the therapy was continued for 70 days. Tumor volume was significantly decreased by [D-Trp6]LH-RH microcapsules or RC-121 given alone. The combination of microcapsules and analog RC-121 caused a greater inhibition of tumor growth than the single agents. Similar effects were seen when the percent increase in the tumor volume was examined. The inhibition of tumor growth caused by the [D-Trp6]LH-RH microcapsules was greater than that caused by RC-121. The combination of the two agents was again the most effective, resulting in the smallest increase in tumor volume. Tumor weights were much lower in the groups treated with microcapsules or RC-121 alone than in controls. The lowest tumor weights were obtained in the group that received the combination of [D-Trp6]LH-RH microcapsules and RC-121. Similar results were obtained in the second experiment, in which the animals were treated for a period of 83 days with microcapsules containing the somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC 160) that released 5 micrograms/day and were injected twice a month alone or in combination with microcapsules of [D-Trp6]LH-RH. Microcapsules of analog RC-160 given alone significantly decreased tumor growth as measured by the final tumor volume, the percentage change from the initial tumor volume, and the reduction in tumor weight. The inhibition of tumor growth induced by [D-Trp6]LH-RH microcapsules was greater than that caused by RC-160. The most striking decrease in tumor weight and volume was obtained in animals treated with microcapsules of [D-Trp6]LH-RH combined with the delayed delivery system for RC-160. The overall response to the combination therapy could reflect the inhibition by somatostatin analogs of the proliferation of prostate cancer cells through a decrease in growth hormone and prolactin release and interference with endogenous growth factors, in addition to the main effect, which is the suppression by [D-Trp6]LH RH of the growth of androgen-dependent tumor cells. Our results indicate that somatostatin analogs enhance the inhibitory effects of [D-Trp6]LH-RH on the growth of prostate tumors. The administration of somatostatin analogs in combination with microcapsules of [D-Trp6]LH-RH might improve clinical response in patients with advanced prostate carcinoma. PMID- 2890166 TI - Inhibition of hydroxymethylglutaryl-coenzyme A synthase by L-659,699. AB - A beta-lactone isolated from Fusarium sp. has been shown to be a potent specific inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase [(S)-3-hydroxy-3-methylglutaryl-CoA acetoacetyl-CoA-lyase (CoA-acetylating), EC, 4.1.3.5] from rat liver. The structure of this beta-lactone, termed L-659,699, is (E,E)-11-[3-(hydroxy-methyl)-4-oxo-2-oxytanyl]-3,5,7-trimethyl-2,4 - undecadienenoic acid. A partially purified preparation of cytoplasmic HMG-CoA synthase from rat liver was inhibited by L-659,699 with an IC50 of 0.12 microM. The enzyme HMG-CoA reductase, beta-ketoacyl-CoA thiolase, acetoacetyl-CoA synthetase, and fatty acid synthase were not inhibited to any extent by this compound. In cultured Hep G2 cells, the compound inhibited the incorporation of [14C]acetate into sterols with an IC50 of 6 microM, while incorporation of [3H]mevalonate into sterols in these cells was not affected. The activity of HMG CoA reductase in the cultured Hep G2 cells was induced in a dose-dependent manner by incubation with L-659,699. A 37-fold increase in reductase was observed after a 24-hr incubation with 62 microM L-659,699. The effect of a number of analogs of L-659,699 on HMG-CoA synthase is also discussed. PMID- 2890167 TI - Engraftment of a clonal bone marrow stromal cell line in vivo stimulates hematopoietic recovery from total body irradiation. AB - Whether bone marrow stromal cells of donors contribute physiologically to hematopoietic stem cell reconstitution after marrow transplantation is unknown. To determine the transplantability of nonhematopoietic marrow stromal cells, stable clonal stromal cell line (GB1/6) expressing the a isoenzyme of glucose-6 phosphate isomerase (Glu6PI-a, D-glucose-6-phosphate ketol-isomerase; EC 5.3.1.9) was derived from murine long-term bone marrow cultures and made resistant to neomycin analogue G418 by retroviral gene transfer. GB1/6 cells were fibronectin+, laminin+, and collagen-type IV+ and collagen type I-; these GB1/6 cells supported in vitro growth of hematopoietic stem cells forming colony forming units of spleen cells (CFU-S) and of granulocytes, erythrocytes, and macrophage/megakarocytes (CFU-GEMM) in the absence of detectable growth factors interleukin 3 (multi-colony-stimulating factor), granulocyte/macrophage colony stimulating factor, granulocyte-stimulating factor, or their poly(A)+ mRNAs. The GB1/6 cells produced macrophage colony-stimulating factor constitutively. Recipient C57BL/6J (glucose-6-phosphate isomerase b) mice that received 3-Gy total-body irradiation and 13 Gy to the right hind limb were injected i.v. with GB1/6 cells. Engrafted mice demonstrated donor-originating Glu6PI-a+ stromal cells in marrow sinuses in situ 2 mo after transplantation and a significantly enhanced hematopoietic recovery compared with control irradiated nontransplanted mice. Continuous (over numerous passages) marrow cultures derived from transplanted mice demonstrated G418-resistant, Glu6PI-a+ stromal colony-forming cells and greater cumulative production of multipotential stem cells of recipient origin compared with cultures established from irradiated, nontransplanted control mice. These data are evidence for physiological function in vivo of a transplanted bone marrow stromal cell line. PMID- 2890169 TI - Fibrinogen and liver function parameters during PGE1-therapy. PMID- 2890168 TI - Carcinogen-induced mdr overexpression is associated with xenobiotic resistance in rat preneoplastic liver nodules and hepatocellular carcinomas. AB - We have previously reported the isolation of a human breast cancer cell line resistant to doxorubicin (adriamycin; AdrR MCF-7 cells) that has also developed the phenotype of multidrug resistance (MDR). MDR in this cell line is associated with increased expression of mdr (P glycoprotein) gene sequences. The development of MDR in AdrR MCF-7 cells is also associated with changes in the expression of several phase I and phase II drug-detoxifying enzymes. These changes are remarkably similar to those associated with development of xenobiotic resistance in rat hyperplastic liver nodules, a well-studied model system of chemical carcinogenesis. Using an mdr-encoded cDNA sequence isolated from AdrR MCF-7 cells, we have examined the expression of mdr sequences in rat livers under a variety of experimental conditions. The expression of mdr increased 3-fold in regenerating liver. It was also elevated (3- to 12-fold) in several different samples of rat hyperplastic nodules and in four of five hepatomas that developed in this system. This suggests that overexpression of mdr, a gene previously associated with resistance to antineoplastic agents, may also be involved in the development of resistance to xenobiotics in rat hyperplastic nodules. In addition, although the acute administration of 2-acetylaminofluorene induced an 8 fold increase in hepatic mdr-encoded RNA, performance of a partial hepatectomy either before or after administration of 2-acetylaminofluorene resulted in a greater than 80-fold increase in mdr gene expression over that in normal untreated livers. This represents an important in vivo model system in which to study the acute regulation of this drug resistance gene. PMID- 2890170 TI - Improving cancer patients' pain control through education. AB - While patient accrual for this study is not yet complete, it appears that the intervention may be helping patients to feel more in control over their pain, take the correct medication dosage and take action to prevent side effects. At this point, the experimental subjects seem much less worried about tolerance to pain medications. The early results suggest some sociodemographic differences in response to pain which, if they persist, should probably be considered as factors in designing patient education programs. PMID- 2890171 TI - A common algorithm for the transduction, amplification and cellular response to photons, hormones, and neurotransmitters. PMID- 2890172 TI - Regulation and role of guanylate cyclase-cyclic GMP in vascular relaxation. AB - Three classes of vasodilators mediate their effects through the activation of guanylate cyclase and the increased synthesis of cyclic GMP. Nitrovasodilators such as nitroglycerin, nitroprusside, hydroxylamine, azide, etc. result in the generation of the nitric oxide free radical that activates the cytosolic (soluble) isoenzyme form of guanylate cyclase. These agents have been useful in increasing cyclic GMP synthesis in numerous model systems and these effects are independent of extracellular calcium. The increased synthesis of cyclic GMP and the activation of cyclic GMP-dependent protein kinase result in the altered phosphorylation of many smooth muscle proteins including the dephosphorylation of myosin light chain, which is associated with vascular and tracheal smooth muscle relaxation. These latter effects may result from cyclic GMP decreasing cytosolic free calcium concentrations and the activity of myosin light chain kinase. Another class of vasodilators, designated endothelium-dependent vasodilators, includes a long list of agents such acetylcholine, histamine, A23187, ATP, thrombin, etc. that relax vessels only when the endothelium is intact. These agents result in the increased endothelial synthesis and/or release of a factor(s) designated endothelial-derived relaxant factor (EDRF), the structure of which is unknown. This labile factor also activates the soluble isoenzyme form of guanylate cyclase in the smooth muscle resulting in cyclic GMP accumulation and the same cascade of events as above. There is evidence that even under basal, non stimulated conditions there is EDRF release that influences vascular tone due to the increased synthesis of cyclic GMP. A third class of vasodilators, atrial natriuretic factor (ANF) or atriopeptins, includes a family of peptides that are produced in cardiac atria and other tissues and influence cardiovascular volume and dynamics by causing natriuresis, diuresis, vasodilation and decreased renin, aldosterone and vasopressin secretion. These peptide hormones also increase cyclic GMP synthesis in vascular, renal, adrenal and other tissues. These effects are mediated through specific ANF receptors that couple to and activate the membrane (particulate) isoenzyme form of guanylate cyclase and increase cyclic GMP-dependent protein kinase activity. There are two ANF receptor subtypes in most cells and tissues that are 130,000 and 66,000 daltons. The ANF receptor of about 130,000 daltons, designated receptor ANF-R1 copurifies with particulate guanylate cyclase through numerous procedures and may be part of the membrane associated guanylate cyclase complex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2890173 TI - Influence of some beta blockers (pindolol, atenolol, timolol and metoprolol) on aggregation and arachidonic acid metabolism in human platelets. AB - The effects of four beta-adrenoceptor blocking agents on platelet aggregation, formation of thromboxane from exogenous arachidonic acid (AA) in platelets, on AA incorporation in platelet phospholipids, and on platelet phospholipase activity were studied. Of the four drugs pindolol inhibited thromboxane formation in a dose-related (0.25-1.0 mM) manner apparently by exerting its influence at the cyclooxygenase (CO) level. This drug also inhibited aggregation induced by AA, collagen, epinephrine and ADP. Atenolol and metoprolol though not showing inhibition of AA-induced aggregation did inhibit collagen- and ADP-induced aggregation; metoprolol reversed ADP-induced aggregation, and abolished second phase of epinephrine-induced aggregation. Timolol did not inhibit aggregation induced by all the aggregating agents. Atenolol inhibited (by ca. 10%) TxB2 formation in platelets from exogenous as well as endogenous AA at rather high concentrations (1.0 mM). Metoprolol and timolol did not do so. The observations reported here can be best explained by taking into account the membrane stabilizing effects and lipophilic properties of the drugs. PMID- 2890174 TI - Effect of histamine H2-receptor antagonists on DNA synthesis in adult rat hepatocytes in primary culture. Cimetidine enhanced hepatocytes proliferation stimulated with insulin and epidermal growth factor. AB - The effects of three of the most widely used histamine H2-receptor antagonists, cimetidine, ranitidine and famotidine, on liver cell growth were studied in vitro using adult rat hepatocytes in primary culture, because these antagonists are commonly given to patients with hepatic cirrhosis or fulminant hepatic failure for protection against peptic ulcers and gastrointestinal hemorrhage. At their clinically effective concentrations in the blood (0.5-5 micrograms/ml cimetidine, 0.25-2.5 micrograms/ml ranitidine and 0.05-0.5 microgram/ml famotidine), these three antagonists did not have any effect on replicative DNA synthesis either in the presence or absence of insulin plus epidermal growth factor (EGF). However, unexpectedly DNA synthesis stimulated by insulin and EGF was found to be enhanced by 0.05-0.5 mg/ml cimetidine, although it was unaffected or inhibited by ranitidine and famotidine at the concentrations tested. Cimetidine caused maximal enhancement of 1.5-2 times the control level of DNA synthesis at a concentration of 0.25 mg/ml. Cimetidine also had an enhancing effect at submaximal concentrations of insulin and EGF, but neither cimetidine nor the other antagonists had any stimulatory effect on DNA synthesis in the absence of insulin plus EGF. This enhancement of DNA synthesis by cimetidine resulted in significant increase in the total DNA content of the hepatocytes in culture. Under the conditions used, cimetidine had the lowest toxicity of these three antagonists and ranitidine the highest, as judged from data on DNA synthesis and the total protein content of cultured hepatocytes, leakage of aminotransferases from the cells and morphological observations. PMID- 2890176 TI - Diagnosis of allergic disease. AB - The diagnosis of allergic disease has to be individualized to each patient. In general, it consists of a good clinical history, a physical examination, and identification of specific relevant allergies by both in vitro and in vivo tests. These will contribute to an assessment of the patient's clinical status and severity of disease. One must always be aware that nonallergic mechanisms can also trigger an attack in atopic individuals. These are clinically indistinguishable from those provoked by an allergen-IgE immune response. We predict that the computer and accurate in vitro tests will join us in our offices. Before the end of this century, this high technology will make the clinical allergist a very precise diagnostician. PMID- 2890175 TI - 2-substituted tetralin derivatives as conformationally restricted butyrophenone analogs. AB - Five related derivatives of 2-(2-piperidinoethyl)tetralin have been synthesized as partially rigid analogs of the neuroleptic butyrophenones. Their in vitro dopamine receptor binding properties and in vivo inhibition of dexamphetamine induced locomotor activity are described. 1-Phenyl-2-(2-piperidinoethyl)-3,4 dihydronaphthalene hydrochloride (8) is about 1% as potent as haloperidol. PMID- 2890177 TI - Practical diagnosis and treatment of allergic and nonallergic rhinitis. AB - Allergic and nonallergic rhinitis is a common chronic disorder affecting children and adults. Effective treatment includes a variety of pharmacologic agents: antihistamines, sympathomimetics, cromolyn, corticosteroids or parenteral immunotherapy. Correct diagnosis is crucial for selecting appropriate and beneficial therapy. PMID- 2890178 TI - Pharmacotherapy of allergic disease. AB - In 1987 the clinician has available to him a wide range of pharmacologic agents with which to treat allergic disease. These drugs used alone or in combination may eliminate or significantly modify allergic symptoms in any organ system. The appropriate use of several drugs in combination can alleviate the need to accept partial resolution of symptoms. However, due to the complexity of some of these agents and the possibility of drug interactions and associated side effects a thorough understanding of their use and pharmacology is needed. PMID- 2890179 TI - Intraoral welding of pure titanium. PMID- 2890181 TI - [Structure and function of blood coagulation factor XIII (transglutaminase)]. PMID- 2890180 TI - [Modification with dyes of the effects of laser irradiation on various enzymes of glutamic acid metabolism]. AB - In the in vivo experiments it has been shown that a mixture of low-intensity helium-neon laser radiation and dyes modifies the effect of laser radiation on the activity of basic enzymes of glutamic acid metabolism. PMID- 2890182 TI - Effect of rioprostil and colchicine on CCl4-acute liver damage in rats. Relationship with plasma membrane lipids. AB - The effects of colchicine (10 g/day p.o. for 7 days) and rioprostil (2-decarboxy, 2-hydroxymethyl-15-deoxy-16-RS-hydroxy-16-methyl-prostaglandin-E1) (20 g/kg s.c., a single dose) on the enzymatic and histological markers of acute liver damage were studied in rats intoxicated with a single oral dose of CCl4. The rats were sacrificed 24 h after CCl4. The lipid composition of the liver plasma membranes was also determined. The increase in Alk. Phosp., GGTP and GPT activities and bilirubin concentration in serum as well as the histological images produced by CCl4 were equally prevented by the treatments with colchicine or rioprostil. CCl4 changed the lipid composition of the liver plasma membrane by increasing PI and PC and decreasing SM, PS and PEA. There was a decrease in the cholesterol/phospholipid ratio at the expense of a reduction of cholesterol/protein ratio and elevation in phospholipid/protein ratio. Colchicine and rioprostil also prevented these lipid alterations. The results suggest that the plasma membrane is an important site of action of CCl4 and of the 2 drugs studied. We postulate that the plasma membrane rather than other organelles is the target for the cytoprotective actions of prostaglandins. PMID- 2890183 TI - The presence and actions of NPY in the canine endocrine pancreas. AB - Immunofluorescent staining for neuropeptide Y (NPY) in canine pancreatic tissue was performed together with an evaluation of the effects of synthetic NPY on the release of insulin (IRI), glucagon (IRG) and somatostatin (SLI) from the duodenal lobe of the canine pancreas in situ. NPY-like immunoreactivity was localized in perivascular nerve fibers throughout the acinar tissue. NPY-immunoreactive fibers were also demonstrated in the islets, usually surrounding blood vessels but also occasionally in fibers associated with endocrine cells, primarily at the periphery of islets. In addition, the ganglia dispersed in the pancreatic parenchyma were densely innervated by NPY-immunoreactive fibers, and these ganglia regularly contained cell bodies staining for NPY. Direct infusion of NPY into the pancreatic artery (p.a.) produced a dose-dependent decrease of pancreatic SLI output and of pancreatic venous blood flow. Low-dose p.a. infusion of NPY (50 pmol/min) had no effect on basal IRI or IRG output or on the islet response to glucose (5-g bolus, i.v.). High-dose p.a. infusion of NPY (500 pmol/min) transiently stimulated IRI output and modestly increased IRG output. However, the comparatively sparse innervation of canine islets with NPY-like immunoreactive fibers and the relatively minor effects of large doses of synthetic NPY on pancreatic hormone release lead us to conclude that this peptide is not an important neuromodulator of islet function in the dog. PMID- 2890184 TI - Somatostatin: peripheral venoconstrictive activity and interaction with monoamines in man. AB - The mechanism of somatostatin venoconstriction and tachyphylaxis in the human hand vein in vivo has been investigated. No cross-tachyphylaxis was observed between somatostatin and 5-hydroxytryptamine, noradrenaline, adrenaline, dopamine or tyramine-induced venoconstriction. Somatostatin potentiates the venoconstrictive activity of noradrenaline, adrenaline and dopamine, but not that of 5-hydroxytryptamine and tyramine. Phentolamine antagonizes the somatostatin induced venoconstriction, whereas methysergide, haloperidol and morphine do not. It is suggested that somatostatin could act on specific receptors in the hand vein, but the mechanism of somatostatin venoconstriction and interaction with vasoactive monoamines remains to be defined. PMID- 2890185 TI - Reduced somatostatin-like immunoreactivity in the brain of dogs with an Eck fistula. AB - Somatostatin-like immunoreactivity (SLI) in the brains of Eck fistula dogs, prepared as an experimental model of hepatic encephalopathy, was measured to investigate the pathogenesis of hepatic encephalopathy. The values were studied in comparison with the concentrations of amino acids where the imbalance was suggested to cause hepatic encephalopathy. SLI levels in the parietal and temporal cortex of Eck fistula dogs were 76.0 +/- 12.0 (mean +/- S.E.M., fmol/mg wet wt.) and 113.4 +/- 23.7, and those of controls were 144.0 +/- 11.8 and 186.9 +/- 19.2, respectively, the differences being statistically significant (P less than 0.005, P less than 0.05). No significant difference in gel filtration profiles of SLI in extracts from parietal and temporal cortex was observed between Eck fistula dogs and controls. Tyrosine and phenylalanine, which are suggested to be precursors of false neurotransmitters, were significantly increased in the parietal cortex of the Eck fistula dogs, and phenylalanine was significantly increased in the temporal cortex of these dogs. There was a significant negative correlation between SLI and phenylalanine concentrations in the parietal and temporal cortex (r = -0.7171, P less than 0.01). These results suggest that the reduced SLI may be one of the factors which cause the neuropsychiatric disturbances in hepatic encephalopathy. PMID- 2890186 TI - [Parkinsonism and dementia]. PMID- 2890187 TI - [Causes of edentulous mouth: retrospective study carried out in the Mont Amba University Hospital]. PMID- 2890188 TI - Psychotropic drug use with successful and unsuccessful community placed developmentally disabled groups. AB - While psychotropic drug use data have been reported for public residential facilities (PRF) and community residential facilities (CRF), no data have been reported for individuals discharged from PRFs and CRFs, especially with respect to how such usage relates to successful and unsuccessful placement. This study reports psychotropic drug use at the time of PRF discharge, at CRFs for successful placements, upon PRF readmission for unsuccessful placements, and factors related to successful and unsuccessful CRF placements. PMID- 2890190 TI - The action of hormones on the rat uterus and mammary gland gamma glutamyltranspeptidase activity. AB - The gamma-glutamyltranspeptidase activity of rat uterus and mammary gland was studied in ovariectomized, hypophysectomized and ovariectomized-hypophysectomized rats under different hormonal and drug treatments. The uterine enzyme appears to be mainly dependent on a direct action of estradiol and the mammary gland enzymatic activity is dependent on prolactin. Our result, however, do not exclude a possible role of estradiol in the regulation of prolactin effects on mammary gland enzymatic activity. PMID- 2890189 TI - The effects of intermittent drug therapy on stereotypy and collateral behaviors of mentally retarded persons. AB - A double-blind, placebo-controlled study was conducted to assess the effects of intermittent drug therapy on stereotyped and collateral behaviors of six profoundly mentally retarded, institutionalized, adult males. The subjects, all of whom had received antipsychotic medication for more than three years, had their maintenance dosages gradually reduced by almost half during the eight-month study. A multiple baseline across subjects design was utilized to assess drug effects on object and body stereotypy and a range of collateral behaviors. While there was individual variation across behaviors and subjects, the main finding was that despite the marked reduction in medication, there were no general changes of clinical significance in any of the behaviors. This finding is of considerable therapeutic importance since a very large number of institutionalized mentally retarded persons receive similar long-term medication for behavior problems and there is some concern regarding the adverse side effects of such treatment. PMID- 2890191 TI - Role of glutathione metabolizing enzymes in nickel mediated induction of hepatic glutathione. AB - The administration of nickel to rats resulted in a dose-dependent increase in the level of hepatic glutathione and in the activities of glutathione reductase and glutathione-S-transferase with a concomitant decrease in the activities of glutathione peroxidase and gamma-glutamyl transpeptidase. The increase in hepatic glutathione may be due to the decrease in the activities of glutathione utilizing enzymes and increase in the activity of glutathione reductase leading to the increased turnover of glutathione. PMID- 2890192 TI - Encomium to the devil. PMID- 2890193 TI - Pituitary adenomas of the multiple endocrine neoplasia type I syndrome. AB - In a series of 1,500 pituitary adenomas surgically resected at Mayo Clinic, 41 (2.7%) occurred in the setting of multiple endocrine neoplasia, type I (MEN-I). Of the 40 patients (18 males, 22 females), 21 (52%) presented with clinical evidence of a pituitary neoplasm, 13 with hyperparathyroidism, and two with functional islet cell tumor. Of the 41 tumors, 11 (27%) were microadenomas, and 30 (73%) were macroadenomas. Immunocytochemical studies demonstrated the following reactivities: GH (4), GH/PRL (6), GH/PRL/glycoprotein (7), GH/ACTH/glycoprotein (1), PRL (16), PRL/TSH (1), ACTH (3), and null cell adenoma (3). We conclude that, in comparison with pituitary adenomas occurring in the general population, those occurring in association with MEN-I are (1) more often endocrinologically functional, (2) more frequently GH- or PRL-producing, and (3) clinicopathologically similar in terms of the subjects age and sex as well as of tumor size and invasiveness. PMID- 2890194 TI - [Personal experiences in the study of thyroid autoimmunity and endocrine exophthalmia]. PMID- 2890195 TI - [Confirmation of the identity of intestinal amoebae and evaluation of the virulence of Entamoeba histolytica by isoenzyme electrophoresis]. PMID- 2890196 TI - [The importance of the medical interview in patients with functional chest pains]. PMID- 2890197 TI - [Treatment of psycho-neuro-autonomic disorders of menopause: contribution of veralipride compared with a barbiturate sedative (proxibarbal)]. PMID- 2890198 TI - Mesalazine tolerance in patients with inflammatory bowel disease and previous intolerance or allergy to sulphasalazine or sulphonamides. AB - Fifty patients intolerant of or allergic to sulphasalazine (SASP) or sulphonamides were treated with mesalazine. Eighty per cent of patients continued treatment during the time of follow-up (mean, 8.4 months); 14% (7 of 50 patients) had to stop the treatment with mesalazine because of side effects. The patients with allergic reactions, including rash, fever, and systemic manifestations from SASP, were most likely to be intolerant of or allergic to mesalazine (four of seven patients); two of them developed a similar reaction from both SASP and mesalazine. Two patients (2 of 12) with previous haematologic side effects had to discontinue mesalazine treatment, one because of mild neutropaenia and one because of an elevation of liver enzyme values. One patient experienced gastrointestinal side effects from both mesalazine and SASP. Altogether, 4 (4 of 50) patients experienced gastrointestinal symptoms from mesalazine. Two of them had had a flare-up of the symptoms of the colitis when treated with SASP. All side effects were rapidly reversible after withdrawal of the drug. Patients with severe allergic reactions with systemic manifestations from SASP should be treated with caution with 5-aminosalicylic acid preparations. PMID- 2890199 TI - Effect of somatostatin on human gastric blood flow evaluated by endoscopic laser Doppler flowmetry. AB - The effect of somatostatin on human gastric blood flow has been evaluated by endoscopic laser Doppler flowmetry. A bolus injection of 250 micrograms somatostatin intravenously caused a transitory decrease in the gastric blood flow of 40%. After continuous infusion of somatostatin for 1 h no change in the gastric microcirculation could be demonstrated in spite of significantly elevated somatostatin-like immunoreactivity in plasma. The results do not give evidence that somatostatin has a possible beneficial effect in patients with gastric bleeding caused by a significant gastric blood flow reduction. PMID- 2890200 TI - [Somatostatin-producing endocrine pancreatic tumor in Recklinghausen's neurofibromatosis. Case report and literature review]. AB - Somatostatin-producing tumors of the pancreas were first described in 1977. In 1983 a syndrome involving multiple endocrine neoplasias (MEN) was named type III A. This syndrome consists of carcinoid of the duodenum, often producing somatostatin, and von Recklinghausen's disease (neurofibromatosis) or pheochromocytoma. The case is reported of a 62-year-old man with familial neurofibromatosis and a tumor of the head of the pancreas spreading into pars II of the duodenum. After Whipple's duodenopancreatectomy the patient exhibited no further symptoms. Immunohistochemistry served to prove the production of somatostatin and small amounts of calcitonin in the tumor. PMID- 2890201 TI - [Hypothalamic factors: recent diagnostic and therapeutic advances]. AB - During the last few years, many neuropeptides have been isolated, characterized and synthesized. Neuroendocrinology is one area in which there has been major progress, particularly through the isolation of two new hypothalamic factors, corticotropin releasing factor (CRF) and growth hormone releasing factor (GRF). CRF specifically stimulates pituitary secretion of ACTH and other peptides derived from pro-opiomelanocortin (beta-lipotropin, beta-endorphin), while GRF, together with somatostatin, controls secretion of the growth hormone. Knowledge of the structures of the hypothalamic factors has allowed the synthesis of the native substances as well as many potent analogues with agonist and antagonist properties. These substances have numerous clinical applications. LHRH or its analogues are presently used or being tested in various conditions such as treatment of hormone-related cancers (prostate, breast), endometriosis, idiopathic precocious puberty as well as in sterility problems. The recent availability of long acting somatostatin analogues has raised great therapeutic expectations in various endocrine and digestive diseases. Whereas GRF can be used in the treatment of short stature, CRF has so far not been shown to be a potential important therapeutic agent. However, its clinical application as a diagnostic test is clearly useful in many situations. There is a promising future for the clinical applications of these substances in various endocrine, digestive and perhaps in psychiatric diseases, and in hormone-related cancers. PMID- 2890202 TI - [Unusual cases of coronary death]. AB - Stenosing coronary artery sclerosis is the most common cause of sudden unexpected death. In this report we present three exceptions: 1. A mycotic coronary aneurysm ruptures and results in pericardial tamponade; 2. in a young woman Takayasu aortitis encroaches on the ostium and mainstem of the left coronary; 3. fibromuscular dysplasia of the right coronary artery causes death in a 56-year old male. PMID- 2890203 TI - [Participation of female colleagues on our panels]. PMID- 2890204 TI - [Regulation of cardiovascular activity by the ventrolateral medulla]. PMID- 2890205 TI - [Advances in the study of the regulation of pancreatic enzymes secretion]. PMID- 2890206 TI - Absence of duplication of chromosome 21 genes in familial and sporadic Alzheimer's disease. AB - The possibility that Alzheimer's disease (AD) is caused by overexpression or duplication of one or more genes on chromosome 21 has been raised by the observation of AD-like neuropathologic changes in individuals with Down syndrome and by the mapping of both the defect for familial AD and the amyloid beta protein gene to this autosome. Possible duplication on chromosome 21 was investigated in both familial and sporadic AD by means of restriction fragment length polymorphisms for the amyloid and SODI loci, as well as for DNA markers in the vicinity of the familial AD defect and in the critical Down syndrome region of chromosome 21. No evidence of increased DNA dosage was observed in either brain or leukocytes of patients with inherited or sporadic forms of AD. Duplication of these regions is therefore not a frequent event in either form of AD. Furthermore, no significant allelic association was detected between AD and any of the loci, including the amyloid and SODI genes, providing no support for the hypothesis that defects in these specific genes are the primary cause of AD. PMID- 2890207 TI - The amyloid beta protein gene is not duplicated in brains from patients with Alzheimer's disease. AB - Complementary DNAs (cDNAs) encoding portions of the amyloid beta protein were used to investigate possible amyloid gene duplication in sporadic Alzheimer's disease. A strategy employing two Eco RI restriction fragment length polymorphisms (RFLPs) detected by the amyloid cDNAs was used. RFLPs allow the detection of a 2:1 gene dosage in the DNA of any individual who is heterozygous for a particular RFLP. The amyloid gene regions homologous to the cDNAs used were not duplicated in the DNA from brains of individuals with sporadic Alzheimer's disease. Similar results were also obtained with a strategy employing a test for 3:2 gene dosage. PMID- 2890208 TI - Molecular genetics: applications to the clinical neurosciences. AB - Application of molecular biology, by means of linkage analysis and DNA probes that demonstrate restriction fragment length polymorphisms (RFLPs), has resulted in the chromosomal localization of the genes responsible for a number of neurological disorders. Characterization of the structure and function of individual genes for these diseases is in an early stage, but information available indicates that the molecular mechanisms underlying phenotypic expression of neurological diseases encompass a wide range of genetic errors ranging from the most minor (a single-base pair mutation) to large chromosomal deletions. Linkage analysis can now be used for genetic counseling in several of these disorders. PMID- 2890209 TI - A DNA segment encoding two genes very tightly linked to Huntington's disease. AB - The discovery of D4S10, an anonymous DNA marker genetically linked to Huntington's disease (HD), introduced the capacity for limited presymptomatic diagnosis in this late-onset neurodegenerative disorder and raised the hope of cloning and characterizing the defect based on its chromosomal location. Progress on both fronts has been limited by the absence of additional DNA markers closer to the HD gene. An anonymous DNA locus, D4S43, has now been found that shows extremely tight linkage to HD. Like the disease gene, D4S43 is located in the most distal region of the chromosome 4 short arm, flanked by D4S10 and the telomere. In three extended HD kindreds, D4S43 displays no recombination with HD, placing it within 0 to 1.5 centimorgans of the genetic defect. Expansion of the D4S43 region to include 108 kilobases of cloned DNA has allowed identification of eight restriction fragment length polymorphisms and at least two independent coding segments. In the absence of crossovers, these genes must be considered candidates for the site of the HD defect, although the D4S43 restriction fragment length polymorphisms do not display linkage disequilibrium with the disease gene. PMID- 2890210 TI - Long-term neuropathological and neurochemical effects of nucleus basalis lesions in the rat. AB - The long-term effects of excitotoxic lesions in the nucleus basalis magnocellularis of the rat were found to mimic several neuropathological and chemical changes associated with Alzheimer's disease. Neuritic plaque-like structures, neurofibrillary changes, and neuronal atrophy or loss were observed in the frontoparietal cortex, hippocampus, amygdala, and entorhinal cortex 14 months after the lesions were made. Cholinergic markers in neocortex were reduced, while catecholamine and indoleamine metabolism was largely unaffected at this time. Bilateral lesions of the nucleus basalis magnocellularis increased somatostatin and neuropeptide Y in the cortex of the rat by at least 138 and 284 percent, respectively, suggesting a functional interaction between cholinergic and peptidergic neurons that may differ from that in Alzheimer's disease. PMID- 2890211 TI - [Drugs against pain]. PMID- 2890212 TI - [Effects of exogenous and endogenous somatostatin on serum insulin concentration in streptozotocin diabetic mice]. PMID- 2890213 TI - [Effect of beta-adrenergic agonist on segmental coronary arterial resistance in the dog]. PMID- 2890214 TI - Selection and characterization of mycophenolic acid-resistant leukemia cells. AB - We isolated four mycophenolic acid (MA) -resistant clones (MA0.4, MA2, MA5, MA20) of murine leukemia (L1210) cells which were 2- to 125-fold more resistant than the parent cells to MA and had a 4- to 50-fold increase in the activity of the enzyme inosine monophosphate dehydrogenase (IMPDase). The MA-resistant phenotype was unstable after passage of MA0.4, MA2, and MA5 without MA, but stable after passage of MA20 without MA. All MA-resistant cell lines lost IMPDase activity after passage without MA. However, only MA20 lost IMPDase activity after passage with MA. The enzyme from all cell lines had similar kinetic parameters. The levels of a single polypeptide of approximately 57,000 daltons was increased in MA5, and the levels decreased after passage of the cells without MA. These results indicate that three of the selected cell lines are resistant to MA because of an increase in the amount of enzyme IMPDase, while the stability of the resistant phenotype of MA20 and its less than expected IMPDase activity that this cell line may have a second mode of resistance. PMID- 2890215 TI - Regional localization of the murine Duchenne muscular dystrophy gene on the mouse X chromosome. AB - The murine locus corresponding to the human Duchenne/Becker muscular dystrophy (DMD) gene has been regionally mapped on the mouse X chromosome by hybridizing DNA from interspecies mouse crosses with a cDNA clone for the mouse Dmd gene. The results demonstrate that the relative organization of genes on the murine and human X chromosomes is more divergent than has previously been postulated. Furthermore, the mouse Dmd gene maps to a similar region of the X chromosome as does the mouse muscular dystrophy mutation mdx, providing further evidence that the mdx mutant may be a murine equivalent of human DMD. However, Southern analysis of portions of the mouse Dmd gene has not yet revealed any differences between mdx and wild-type mice. PMID- 2890216 TI - [Hormonal function of the gastrointestinal tract]. PMID- 2890217 TI - [Advantages and disadvantages of drug combinations in cardiovascular therapy]. PMID- 2890218 TI - Electroimmunoassay of prothrombin. AB - Electroimmunoassay of normal (10-Gla) and Gla-deficient prothrombins containing 0 to 9 Gla (gamma-carboxyglutamyl) residues performed in EDTA against anti- (normal) prothrombin showed that each of the Gla-deficient proteins contained as much antigenic activity as does the normal molecule. In the presence of Ca2+, however, normal prothrombin appeared to show the least while 0- to 2-Gla variants, the most activity. This anomaly arises from the presence of antibodies (Ca-IIAb) which form antigen-antibody (Ag-Ab) complexes when the conformation of the antigen is stabilized in Ca2+. For example, upon fractionation of the antisera and mixing Ca-IIAb (bound to 10-Gla prothrombin, Affi-gel column and eluted by replacing Ca2+ with EDTA) with those reacting with prethrombin1 (non Gla portion of the molecule), rocket heights in Ca2+ decreased the most with 10- and 9-Gla (32%), followed by 13% with 8-Gla, 2% with 7-Gla and none with 2-Gla prothrombins--indicating that Ca-IIAb do cross react with 7-, 8- and particularly 9-Gla prothrombins. This was also confirmed by the fact that anti 7-Gla but not anti 0-Gla sera contained some antibodies which reacted only in the presence of Ca2+. PMID- 2890219 TI - Monoclonal antibodies to prothrombin. AB - Hybridoma technology was used for the production of murine monoclonal antibodies to bovine normal prothrombin. Hybrid cell cultures were assayed for the production of antibodies, both in the absence and presence of calcium ions, by Enzyme-Linked Immunosorbent Assay (ELISA). Antibody-producing cell lines were cloned two times and grown as ascites tumors. Monoclonal antibodies (McAb), isolated by affinity chromatography (Protein A-Sepharose), were tested for their affinity for normal (10-Gla) and dicoumarol-induced abnormal prothrombins containing 2, 5, 7, 8 and 9 gamma-carboxyglutamyl (Gla) residues. A total of 24 McAb were obtained and the immunoglobulins were of the IgG1 subclass. Nine of the twenty-four McAb did not require Ca2+ for the formation of Ag-Ab complexes, and reacted equally with normal and Gla-deficient prothrombins. These antibodies had affinity for prethrombin1 (P1) but not for the Gla-containing prothrombin fragment1 (F1) portion of the molecule. In contrast, the 15 Ca2+-dependent McAb reacted with F1 but not with P1. They discriminated the abnormal prothrombins based upon their Gla content. For example, though all the Ca2+-dependent McAb formed Ag-Ab complexes with 9-, essentially none formed with 5- or less-Gla prothrombins. [Some reacted equally with 9- and 10-Gla (normal) prothrombin while others had only 25% of normal affinity for 9-Gla isomer]. Only four and twelve of the 15 McAb had some affinity for 7- and 8-Gla variants, respectively. These results show that antibodies which react with the Ca2+-stabilized conformation of prothrombin are not specific for normal prothrombin, as has been reported in the literature. PMID- 2890220 TI - [The non-scrotal testis]. AB - In this article the classification of the nonscrotal testis is elucidated with a description of all forms of incomplete testicular descent. A great deal of attention is paid to the process of reaching the proper diagnosis, outlining the procedure for physical examination. The risk of infertility, the rather rare occurrence of testicular tumor, and a disturbance of the psychosexual development, are reasons why the undescended testis should be treated. How the undescended testis should be treated, hormonal or surgical, depends entirely on the position of the testis. LHRH nasal spray may induce descent in testes that have emerged from the inguinal canal and can be manipulated to at least the scrotal entrance. Surgical treatment is indicated for all undescended testes that have not emerged from the inguinal canal as well as all ectopic testes, and for those testes that failed to descend with hormonal therapy. The treatment protocol for all types of nonscrotal testes is discussed and schematically presented. PMID- 2890221 TI - HLA class I- like antigen expression on human leukemic cells. AB - The expression of HLA class I- like molecules was analyzed on human acute and chronic leukemic cells. The presence on leukemic cells of class I- like molecules, absent on the patient's normal lymphocytes, was examined by complement dependent lymphocytotoxicity using platelet absorbed alloantisera that recognize HLA-linked, 45-12 kd, beta-2-microglobulin associated molecules, selectively expressed on PHA-activated cells. A positive reactivity of the anti- class I- like alloantisera was found in 50% of the acute leukemias (cALL, T-ALL and AML), independently of the lineage of differentiation, while chronic lymphocytic leukemias (B-CLL) were constantly negative. It is suggested that beta-2 microglobulin associated HLA molecules may represent markers of leukemic blast activation and/or maturation state. PMID- 2890222 TI - Two alleles detected for HLA-DZ alpha on the basis of a polymorphic restriction site in the third exon. AB - The restriction enzyme ApaI has been used to define Restriction Fragment Length Polymorphism (RFLP) within the DZ alpha gene. Digestion of genomic DNA of 96 individuals with ApaI reveals the existence of two different patterns. Both homozygous and heterozygous individuals were detected. Hardy-Weinberg analysis indicates that DZ alpha is part of a di-allelic system with allele frequencies of 50%. DZ alpha polymorphism in the population studied does not correlate with serologically determined class I and HLA-DR, DQ and cellular DP typing data. A limited family study demonstrates that DZ alpha polymorphism segregates with HLA class II phenotypes. PMID- 2890223 TI - Endocrine cells of gastric aberrant pancreas by PAP staining method. AB - Histopathological classification of gastric aberrant pancreas has been done by Heinrich's criteria. However in some case it was difficult to detect incomplete Langerhans' island consisting of several endocrine cells or a single endocrine cell by usual H-E staining. To identify the distribution of incomplete Langerhans' islands and endocrine cells, we applied an enzyme antibody method utilizing PAP method for 7 cases of gastric aberrant pancreas. It became easy to identify the endocrine cells such as single cell and islet cells by using the PAP method. In all 3 cases of aberrant pancreas classified as Heinrich type II and one of 2 case of type III, Langerhans' islands or endocrine small cell groups and single cells were found. The PAP staining method was useful to determine the Heinrich's classification of the aberrant pancreas. PMID- 2890224 TI - Kainic acid as a tool to study the regulation and function of opioid peptides in the hippocampus. AB - Kainic acid (KA), an excitatory neurotoxin, was used as a tool to study the metabolism of hippocampal opioid peptides and their functional role in the expression of wet-dog shakes (WDS). A single intracerebral injection of KA (1 microgram/rat) caused recurrent motor seizures lasting 3-6 h. During the convulsive period, native Met5-enkephalin-like (ME-LI) and dynorphin A(1-8)-like (DYN-LI) immunoreactivities in hippocampus decreased by 31 and 63%, respectively. By 24 h after dosing, the hippocampal opioid peptides had returned to control levels, and by 48 h ME-LI had increased 270% and DYN-LI 150%. Immunocytochemical analysis revealed that ME-LI and Leu5-enkephalin-like (LE-LI) immunostaining in the mossy fibers of dentate granule cells and the perforant-temporoammonic pathway had decreased visibly by 6 h and had increased markedly by 48 h following KA. A visible decrease in DYN-LI in mossy fiber axons within 6 h was followed by a substantial increase at 48 h. To determine whether the increases in hippocampal ME-LI reflected changes in ME biosynthesis, levels of mRNA coding for preproenkephalin (mRNAenk) and cryptic ME-LI cleaved by enzyme digestion from preproenkephalin were measured. Following the convulsive period (6 h), mRNAenk was 400% of control, and by 24 h, cryptic ME-LI was 300% of control. Increases in native and cryptic ME-LI and in mRNAenk were also noted in entorhinal cortex, but not in hypothalamus or uninjected striatum. Our data suggest that KA-induced seizures cause an increase in ME release, followed by a compensatory increase in ME biosynthesis in the hippocampus and entorhinal cortex. Several lines of evidence from this study have suggested that hippocampal enkephalins are intimately related to KA-elicited WDS. The shaking behavior was attenuated by pretreatment with naloxone or antisera against [Met5]-enkephalin. We also observed that KA-induced WDS can be mimicked by intrahippocampal injection of enkephalin-related peptides. Furthermore, this study demonstrated that intact dentate granule cells are essential for KA- and enkephalin-induced WDS, since a colchicine injection into the ventral hippocampus, which selectively destroys granule cells, abolished this behavior. PMID- 2890225 TI - Development of Thy 1 positive mouse thymocytes. Analysis of early fetal thymocytes by flow microfluorometry. AB - Early mouse fetal thymocytes were analyzed for cell size and amount of Thy 1 by flow microfluorometry. There were very few Thy 1 positive cells in the embryonic thymus of the 13th day; in the 14th day fetal thymus, the number of Thy 1 positive cells increased, though the Thy 1 content remained at relatively low levels. Both the number of Thy 1 positive cells and the content of Thy 1 greatly increased by the 15th day, but the Thy 1 content was still definitely lower than that of adult thymocytes. These results indicate that Thy 1 negative thymocyte precursors increase in Thy 1 content gradually when they differentiate into thymocytes. The present study also suggests that immature thymocytes like the 15th day fetal thymocytes, even though they are definitely Thy 1 positive, bear Thy 1 at much lower levels than most of the adult thymocytes, indicating a distinct difference in Thy 1 content between immature thymocytes and most of the adult thymocytes. PMID- 2890226 TI - Facilitation of syngeneic stem cell engraftment by anti-class I monoclonal antibody pretreatment of unirradiated recipients. AB - We have established a murine model of syngeneic bone marrow transplantation based on the use of monoclonal antibody as the sole conditioning regimen in unirradiated recipients. Administration of a single injection of monoclonal antibody directed against major histocompatibility complex-encoded class I determinants facilitated permanent hemopoietic stem cell engraftment without any apparent side-effects. Whereas untreated hosts exhibited a maximal chimerism of 15% at donor cell doses of up to 12 X 10(7) bone marrow cells, pretreatment by 2 mg of anti-class I antibody one week prior to transplantation of 3 X 10(7) syngeneic bone marrow cells resulted in a mean donor representation of about 80%. The antibody can be given up to four weeks prior to transplantation, and the degree of donor engraftment observed is a function of the dose of antibody administered. The fact that specific antibody enhanced engraftment in two strain combinations indicates that antibody is the active agent in facilitating engraftment and that facilitation is not strain-restricted. Anti-class I antibodies of the IgG2a, but not IgG1, isotype are effective in promoting engraftment. Although the isotype requirement suggests a role for antibody mediated cytotoxicity in promoting stem cell engraftment, the extensive time frame of facilitation suggests that other effects of the antibody may also be involved. The model of syngeneic bone marrow transplantation we describe here will be useful in studying the mechanisms regulating stem cell engraftment and may have potential clinical application as an approach to autologous marrow transplantation. PMID- 2890227 TI - Autologous stem cell transplantation using peripheral blood stem cells. PMID- 2890228 TI - [A favorable outcome of intestinal necrosis caused by periarteritis nodosa]. PMID- 2890229 TI - Enterotoxaemia in water buffaloes caused by Clostridium perfringens type A. PMID- 2890230 TI - T-cell lymphomas of the stomach: morphological and immunological studies characterizing two cases of T-cell lymphoma. AB - Using cytochemical, electron microscopic and immunohistochemical techniques in 20 primary malignant lymphomas of the stomach, we found 18 B-cell and 2 T-cell lymphomas. Primary T-cell lymphoma in the stomach has not been previously reported. The T cells in both cases were reminiscent of T immunoblasts with prominent nucleoli and a basophilic cytoplasm. Case 1 showed a cytological relationship to pleomorphic T-cell lymphoma, large cell type. Case 2 contained in addition some cells not previously described in T-cell lymphomas, resembling immature plasma cells with abundant rough endoplasmic reticulum. Focal positivity to acid phosphatase and dipeptidylaminopeptidase IV suggests the T-cell nature of both lymphomas. In both cases the tumour cells were OKT 11 and OKT 4 positive, and negative for OKT 8. Thus, both cases represent high-grade malignant T-cell lymphomas which correspond phenotypically to T-helper cell lymphoma. Case 2 revealed a further immunohistochemical peculiarity: atypical immunoblasts reacted positively with Ki-1 antibody. Thus, it is a Ki-1 lymphoma of T-cell type. PMID- 2890231 TI - The establishment and characterization of two new cell lines derived from a single human colonic adenocarcinoma. AB - Two cell lines with different in vitro growth characteristics were established from a single mucinous colonic adenocarcinoma. Epithelial cells of the line 5583 E demonstrated anchorage-dependent growth while those of line 5583-S were anchorage-independent and grew as multicellular floating spheroids. Both cell lines shared common characteristics with respect to the expression of differentiation markers (secretory component, carcinoembryonic antigen), mucins and karyotype (trisomy 12 and 14, marker chromosome) but also showed consistent differences. In nude mice 5583-S cells formed moderately differentiated mucinous adenocarcinomas with high carcinoembryonic antigen and mucin production, whereas 5583-E xenografts were poorly differentiated and almost entirely failed to produce carcinoembryonic antigen and mucins. The plating efficiency of 5583-E cells appeared to be greater and doubling time shorter than those of 5583-S cells. Furthermore, 5583-E cells showed an extra isochromosome, 1q. The cell lines were genotypically and phenotypically stable over a period of 2 years. Our results reemphasize that multiple cell lines with heterogeneous phenotypic and genotypic characteristics can be obtained from a single primary tumor. PMID- 2890232 TI - Effect of estrophilic platinum complex on the mouse uterus. AB - Resistance of hormone-dependent mammary carcinoma to cisplatin as a potent antitumor agent led to the synthesis of other estrophilic platinum complexes. In this investigation, the effects of a newly synthesized estrogen-receptor affine platinum complex on the mouse uterus were studied using light and electron microscopy. The results have been compared with Tamoxifen, cisplatin and the estrophilic ligand. Both estrophilic ligand and estrophilic platinum complex produced strong estrogenic effects as well as features characteristic of the uterine epithelial cell in the luteal phase of the cycle, corresponding to a massive stimulation of the surface and glandular epithelial cells. The uteri showed large glandular lumina. An increase in the number of multivesicular and residual bodies, accompanied by a proliferation of eosinophilic granulocytes, was also seen. The appearance of inter- and intracellular lumina and the activation of smooth muscle cells represent further characteristic effects of the estrophilic ligand and estrophilic platinum complex. Anticipated increases in the incidence of cell death and/or deviant cyto-nuclear architecture in the uteri treated with cisplatin or platinum complex, were not observed. PMID- 2890234 TI - Morphometric study of alterations of extrafocal hepatocytes of rat liver treated with N-nitrosomorpholine. AB - Male Sprague-Dawley rats were treated with the hepatocarcinogen N nitrosomorpholine for 7 weeks and observed for up to 40 weeks after withdrawal of the carcinogen. In addition to the focal preneoplastic lesions described earlier there were also alterations in extrafocal hepatocytes and these changes have been quantified morphometrically. Since the periportal and perivenous hepatocytes were not altered to the same extent, cells of the periportal zone (PPZ) and cells of the perivenous zone (PVZ) were measured separately. Immediately after stopping treatment there was marked enlargement of the hepatocellular cytoplasm and of the nuclei in both the PPZ and the PVZ and a reduction in the number of binuclear hepatocytes. While these alterations were totally reversed during the first 10 weeks after treatment ceased in the PPZ, statistically significant changes in nuclear size, nuclear-cytoplasmic ratio and number of binuclear cells persisted in the PVZ up to 40 weeks after the end of treatment. We suggest that both the foci of altered hepatocytes as well as the persisting changes in extrafocal hepatocytes may be involved in the process of hepatocarcinogenesis. PMID- 2890233 TI - Ultrastructural observations in the carbonyl iron-fed rat, an animal model for hemochromatosis. AB - Rats fed a carbonyl iron-supplemented diet for 4-15 months were studied for iron content and morphologic changes in the liver, spleen, intestinal mucosa, pancreas and heart. All organs had an increased iron content measured by atomic absorption, with the highest concentrations in the liver and spleen. The periportal distribution of stored iron in the liver was similar to that in human hemochromatosis. In animals treated beyond 6 months Kupffer cells and sinusoidal lining cells also showed cytosiderosis. Electron microscopy provided information on ferritin and hemosiderin content and distribution within parenchymal and sinusoidal cells of the liver but no excessive fibrosis was found. Except for the spleen, the other organs showed less iron deposition. Iron-filled lysosomes (siderosomes) were found in macrophages in the intestinal lamina propria and pancreas, as well as in enterocytes, pancreatic acinar cells and heart muscle cells. Heavily iron-laden siderosomes had increased membrane instability which was demonstrated both morphologically and by measurements of latent lysosomal enzyme activities. Even though cirrhosis was not found, the distribution pattern of accumulated storage iron and lysosomal lability indicated that the carbonyl iron-fed rat is a suitable experimental model for human hemochromatosis. PMID- 2890235 TI - Estimates of the number of clonogenic cells in crypts of murine small intestine. AB - There is a proliferative cell hierarchy in the mouse intestinal crypt with ancestral stem cells which can regenerate all components of the lineage after injury (clonogenic cells). The number of these clonogenic or regenerative cells per crypt can be estimated from radiobiological experiments where doses of radiation are used to kill cells and ablate crypts. Various approaches can be adopted which provide different estimates of this number of cells. One of the conventional approaches used in the past provided estimates of about 70-80 clonogenic cells per crypt (i.e. about 50% of the proliferative or 30% of all crypt cells). A technically simpler approach has recently been suggested. This has been used here to provide many independent estimates of the number of crypt clonogenic cells. These suggest about 32 clonogenic cells exist per crypt i.e. about half the previous estimate and about twice the number of putative "functional" stem cells (those which operate as stem cells in the normal steady state crypt). The reasons for the differences are discussed. The new estimates are compatible with the hypothesis that the crypt contains a ring of about 16 functional stem cells which are expected to be clonogenic, besides which there is a second ring of 16 clonogenic cells which represent early transit cells (the immediate daughters of the stem cells) which can act as clonogenic cells if required after radiation injury. PMID- 2890236 TI - Calcium antagonists and heat-induced hepatic injury. AB - Several laboratories have demonstrated the value of the isolated perfused rat liver as a suitable model for heat-induced hepatic injury in vivo. Membrane changes caused by perfusion of rat livers at 42 degrees C for 90 min were similar to those induced by toxic chemicals or hypoxia. In an evaluation of several categories of drugs reported to reduce cell injury, calcium antagonists (nifedipine, dantrolene, and verapamil), were evaluated for their therapeutic potential for heat injury. Isolated rat livers were perfused at 42 degrees C for 90 min with and without calcium antagonists. Livers were also perfused at 37 degrees C. Potassium and transaminase leakage, bile production and ultrastructure were used to evaluate their responses. Neither of the three calcium antagonists significantly improved any of the functional parameters measured. However, dantrolene produced dilated or vesicular rough endoplasmic reticulum in the heated livers. These changes suggest selective intracellular action on endoplasmic reticulum of heated livers. Ring-shaped mitochondria and vesicular endoplasmic reticulum were observed in the heated, verapamil-treated livers, but these could not be quantitatively distinguished from controls. Nifedipine did not appear to alter intracellular membranes, but did increase bile production. PMID- 2890237 TI - Autointerference in silver accumulation in macrophages without affecting phagocytic, migratory or interferon-producing capacity. AB - Silver accumulation and processing in mouse peritoneal macrophages was studied in vitro by autometallographic visualization of intracellular silver. During the first 24 h of incubation in a medium containing from 5 microM to 20 microM of silver lactate, an inverse relationship between silver concentration in the former and visualizable silver in macrophages was recorded. Later, however, the cells treated with higher silver concentrations accumulated most silver. Cells exposed to silver concentrations above these levels exhibited acute coagulation necrosis and disintegrated within the first 15 min of silver treatment. Macrophages treated with silver lactate concentrations not causing acute cytotoxicity showed no impairment of their phagocytic, migratory or interferon producing capacities. The significance of autointerference in silver accumulation and processing in macrophages is discussed, and a functional defect in the lysosome/phagosome system is suggested as a basis for the phenomenon. PMID- 2890238 TI - No evidence for involvement of plasma proteins or blood-borne cells in amyloid plaque formation in scrapie-affected mice. An immunohistoperoxidase study. AB - The present study was designed to investigate blood-brain permeability and the possible involvement of plasma proteins and blood-borne cells in amyloid plaque formation in scrapie-affected mice. No abnormal extravasation of intravenously injected horseradish peroxidase (HRP) was found and with immunocytochemical techniques no plasma proteins were detected in neuropil from scrapie-affected mice. In contrast to an earlier report, these findings suggest that the blood brain barrier is essentially intact in scrapie-affected mice. Using immunohistochemical and enzyme histochemical methods no cells belonging to the monocyte-macrophage lineage were detected in association with amyloid plaques. Thus, by these methods there was no evidence that plasma proteins or blood-borne cells are involved in amyloid plaque formation in scrapie-affected mice. However, astrocytes were consistently found to be associated with amyloid plaques at all stages of their development. PMID- 2890239 TI - DNA-cytophotometry of benign compound and intradermal naevi, Spitz epithelioid naevi and malignant melanomas. AB - Single cell DNA cytophotometry was used to characterize seven compound, ten intradermal and six Spitz naevi as well as 23 primary cutaneous malignant melanomas. Compound and intradermal naevi were characterized by a smaller nuclear area than both Spitz naevi and malignant melanomas. Tumour ploidy could not be used as a single criterion of malignancy since both diploid and hyperdiploid melanomas were encountered. The very low mean optical density of Spitz naevi served to distinguish these lesions from malignant melanomas. PMID- 2890240 TI - [Treatment of nocturnal enuresis]. PMID- 2890241 TI - Pharmacokinetics of loprazolam and its principal metabolite in young subjects and elderly hospital patients. AB - 1. The pharmacokinetics of loprazolam and its principal pharmacologically active metabolite, the piperazine N-oxide, were compared in young subjects (aged 21-25 years) and elderly patients (aged 63-86 years) following single oral evening doses (0.5 mg and 1 mg). 2. Plasma loprazolam was assayed by a specific h.p.l.c./g.c. method. The N-oxide metabolite was assayed by gas chromography. 3. Mean times to peak plasma concentration of loprazolam did not differ significantly between young and elderly subjects and ranged from 1.6-2.7 h. There was, however, a longer mean time to peak concentration of the N-oxide metabolite in the elderly but this was only statistically different after the 0.5 mg dose (4.5 mg young, 6.4 h elderly). 4. Mean peak plasma concentrations of loprazolam did not differ significantly between young and elderly nor did plasma concentrations of the N-oxide metabolite. 5. Although the mean elimination half life of loprazolam was not statistically significantly different between young and elderly subjects (range 10.9-16.0 h) there was a trend towards somewhat longer half-lives in the elderly. Furthermore, there was a small but significant increase in the half-life of the N-oxide metabolite in the elderly after the 1 mg dose from 11.7 h to 16.7 h. 6. The areas under the plasma concentration time curves for both loprazolam and its N-oxide were greater in the elderly being some 50-68% (mean 132.0 and 111.5 ng/ml h) above those found in young subjects (mean 89.8 and 66.0 ng/ml h).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890242 TI - Almitrine bismesylate. AB - There is a place in therapy for an orally active respiratory stimulant. Almitrine bismesylate is a respiratory agonist which: 1. Effectively increases PaO2 in a unique way, principally by stimulation of the peripheral chemoreceptors. 2. Appears to have an effect on blood gases through mechanisms other than stimulation of ventilation which could be on ventilation-perfusion relationships, or even metabolic, for which there is as yet no firm evidence. 3. After chronic administration has a plasma elimination half-life of 20-30 days. This could result in plasma accumulation of the drug, and means that drug intolerance problems are not readily resolved by stopping the tablets. Special dosing schedules may be required. 4. Has an action on the pulmonary vasculature which is mainly vasoconstrictor (and vasodilator in acute hypoxia in animal studies). Present evidence regarding the effect of long-term administration on pulmonary haemodynamics is conflicting. 5. May have an adverse, possibly dose-related effect on dyspnoea in some patients - more work is needed on patient characteristics associated with good drug tolerance. 6. Has an adverse effect on peripheral nerve function in some patients. Whether this is de novo, or aggravation of a preexisting lesion has yet to be established. Thus, although almitrine is effective in increasing PaO2 and as an experimental drug is fascinating, its clinical use remains to be clearly defined. The most powerful argument for the therapeutic use of almitrine would be the demonstration of a beneficial effect on mortality; either in acute exacerbations of respiratory failure, or in the same way as LTO2 exerts an effect in chronically hypoxaemic patients. PMID- 2890243 TI - [Drug treatment of rheumatoid arthritis and osteoarthritis]. AB - A review is given about more recent methods for therapy of the rheumatoid arthritis as well as of the osteoarthrosis. Of a large importance in the treatment of the rheumatoid arthritis and of the osteoarthrosis is the method of clinical tests of non-steroidal antirheumatic drugs and of the so-called disease activity modifying substances. Own experiences and results of controlled, clinical open and double-blind studies were given. PMID- 2890244 TI - Acellular pertussis vaccine prepared by a simple extraction and toxoiding procedure. AB - An extract containing predominantly pertussis toxin (PT) and filamentous haemagglutinin (FHa) was obtained from culture supernates of Bordetella pertussis by a single-step procedure using dye-ligand chromatography. The pathophysiological activities associated with the pertussis toxin component were removed by treatment with a water-soluble carbodiimide. The product was stable at 4 degrees C, was non-toxic for mice, induced high levels of IgG antibodies to both PT and FHa in vaccinated animals as judged by ELISA, and protected mice from intracerebral and intranasal challenge with B. pertussis. PMID- 2890245 TI - [Guanylate cyclase--its functions normally and in pathology]. PMID- 2890246 TI - [Comparison of the pathological manifestations of higher nervous activity and the molecular biology processes of the brain in the dynamic development of experimental neuroses]. PMID- 2890247 TI - [Pathogenetic problems of experimental neuroses]. PMID- 2890248 TI - [Intracellular functions of neurotransmitters. The phylo- and ontogenetic aspects]. AB - The neurotransmitters found in early ("pre-nervous") embryos of Metazoa operate at the intracellular level. In these embryos, the transmitter receptors (or their functional equivalents) and adenylate cyclase coupled with them are localized intracellularly. Intracellular functions of neurotransmitters may be also found in the differentiated neurons of adult animals. PMID- 2890249 TI - [Mitogenic action of the liquid phase of a microbial suspension of Bordetella pertussis]. AB - The suspension of B. pertussis cells in 0.15 M NaC1 solution, used for the preparation of corpuscular pertussis vaccine contains components loosely bound to microbial cells and producing pronounced mitogenic effect on mouse splenocytes at a concentration of 10 micrograms/ml. The mitogenic activity of B. pertussis is due to complex substances (lipopolysaccharide, protein, nucleic acids) with a wide range of molecular weights (70,000 to greater than 400,000). The mitogenic factor showing no leukocyte-stimulating and protective activity has been isolated by sedimentation with ammonium sulfate and gel filtration on Sephadex G-200. The mitogenic activity of B. pertussis lipopolysaccharide in the blast transformation test has been confirmed. PMID- 2890250 TI - [Adhesion of Bordetella pertussis]. PMID- 2890251 TI - [Metabolic characteristics of brain proteins and neuromediators in the late postresuscitation period]. AB - Interferometric and cytophotometric examination of the neurons of the motor area of the cerebral cortex and caudate nucleus in dogs in the late postresuscitation period has revealed a significant decrease in protein concentrations and activity of acetylcholinesterase (ACE), an increase in the activity of acetylcholinesterase (ACE), an increase in the activity of monoamine oxidase (MAO) and size of the cells of layers III and V of the motor cortex and caudate nucleus type I Golgi's neurons 12 days after clinical death. One month after resuscitation the protein concentrations were considerably higher than the normal values, levels of ACE normalized, levels of MAO in layer III of the motor cortex normalized but rose drastically in layer V and in the caudate nucleus. Neurons in type I Golgi's cells and in layer III of the motor cortex diminished in size. On the basis of their own and literature date the authors conclude that the motor cortex neurons are more sensitive to conditions of the terminal status than the caudate nucleus neurons and that protein metabolism and that of neuromediators interact in the process of restoration of the patient's neurological status. PMID- 2890252 TI - Toxicity of mosquitocides on freshwater mussel larvae. AB - The effect of four insecticides also used for mosquito-killing (Fyfanon ULV, K Othrin ULV, Unitox 7 ULV and Unitox 20 ULV) was studied on the larvae (glochidia) of two freshwater mussel species, Anodonta cygnea and Anodonta anatina. In addition to the determination of the 24-96 h LC50 values of the insecticides, studies were also performed on their effect exerted on a physiological process, the tryptamine-(TA)-induced activation of the larvae in normal and 24 h test. On the basis of the LC50 values, Fyfanon and Unitox 20 were found to be the most toxic to the studied mussel larvae, however, the TA-induced adductor muscle activity, as physiological process, was also inhibited by Unitox 7 in relatively low concentrations. This effect may reduce the chance of further development of the larvae, by exerting harmful effect on the number of freshwater mussels. PMID- 2890253 TI - [Chlordesmethyldiazepam as an anesthesia-inducing agent: time of loss of consciousness. Statistical analysis in man]. AB - .1 mg/kg e.v. of chlordesmethyldiazepam, a 1.4 benzodiazepine derivative, were given in induction of anaesthesia of 60 plastic-reconstructive surgery patients respectively in 30 (Group 1.30 patients) and in 60 sec (Group 2.30 patients) to assess the times to spontaneous closing of the eyes and to disappearance of the palpebral reflex. It is concluded that the reflex times are not significantly different in both groups. PMID- 2890254 TI - [Sensorimotor polyneuropathy induced by almitrine dimesylate. Anatomo-clinical study of a case]. AB - A 65-year-old male patient with chronic obstructive long disease developed a severe motor and sensory polyneuropathy during the treatment with almitrine bismesylate (Vectarion). Electrophysiological and neuropathological investigations demonstrated a distal axonopathy. A medicamentous origin was suspected since other causal factors were lacking. Eight months after stopping of treatment, the functional recovery was complete. The authors discuss the recent data recorded in the literature concerning the neurological complications induced by this new drug, which is increasingly administered in diseases of the respiratory tract. PMID- 2890255 TI - No antibodies to HTLV-I and HIV in patients with dementia in Finland. AB - Patients with human immunodeficiency virus (HIV) have often progressive dementia. Human T cell lymphotropic virus Type I (HTLV-I) infection has not been reported to cause dementia. We tested antibodies to HTLV-I and HIV in serum and cerebrospinal fluid in 69 Finnish patients referred because of dementia to an outpatient department of neurology. No antibodies to HTLV-I and HIV were detected in patients with the clinical diagnosis of Alzheimer's disease, vascular dementia, secondary dementia due to a specific cause, or in cases of atypical dementia. PMID- 2890256 TI - Possibilities of immunohistochemical investigation on human temporal bone. AB - After preliminary studies on human tonsillar tissue, lymph node tissue, or tissue from the appendix, it could be shown that after a fixation in Bouin solution or in sublimate-formaldehyde solution and subsequent embedding of the tissue in paraffinwax, the structure of the immunoglobulins present in the tissue remains intact. Even after long-term decalcification of the fixed tissue in EDTA, its structure does not alter and the immunoglobulins can be detected in high dilution either by the direct immunofluorescence method or with peroxidase-antiperoxidase. Human temporal bones from healthy individuals were fixed in Bouin solution or in sublimate-formaldehyde solution and incubated for sufficient time in EDTA decalcification solution until they were radiologically free of calcium. After embedding in paraffinwax or Paraplast, the immunoglobulins of the middle ear mucosa could be identified with the immunohistochemical methods described above. For the first time, localized immunoglobulins including the secretory component in the endolymphatic sac could also be demonstrated. The method is so sensitive that the binding of antibodies from the serum of patients with possibly immunopathological inner ear conditions can be detected by means of the indirect immunofluorescence test. Furthermore, other immunohistochemical assay methods can also be carried out with these methods (e.g. neuropeptide detection. PMID- 2890257 TI - The mumps-specific T cell response in healthy individuals and insulin-dependent diabetics: preferential restriction by DR4-associated elements. AB - An increased frequency of mumps-specific T lymphocytes restricted by DR4 associated elements has previously been described in DR4 heterozygotes. Here we report that the preferential restriction elements may be present on DR4 molecules expressing either Dw4 or Dw14. No particular genomic DQ-beta-polymorphism was associated with the preferential restriction elements. PMID- 2890258 TI - Effect of some benzodiazepines on the secretion of thyrotropic hormone and prolactin under conditions of experimental stress. AB - The effects of diazepam and medazepam, administered repeatedly orally, on the secretion of thyrotropic hormone and prolactin in male sexually matured albino rats were investigated under conditions of acute cold and immobilization stress. The agents were administered for 30 days in doses of 1 and 5 mg/kg for diazepam, and 1 and 10 mg/kg for medazepam. Sixty minutes after the last injection, the animals were placed under conditions of low temperature--+4 degrees C (cold stress) and of immobilization (immobilization stress) for 60 min. The content of thyrotropic hormone (TTH) and of prolactin in the serum of the control and experimental animals was determined using radioimmunological methods. Diazepam and medazepam were found to inhibit prolactin secretion under stress, affecting TTH secretion only in high doses: 5 mg/kg diazepam and 10 mg/kg medazepam. The TTH content was reduced under conditions of cold stress. The role of GABA and of the benzodiazepine receptors in the central nervous system in the regulation of the secretion of prolactin and TTH under states of stress is discussed. PMID- 2890259 TI - Glucose transport into skeletal muscle. Influence of contractile activity, insulin, catecholamines and diabetes mellitus. AB - The influence of contractile activity, insulin, catecholamines and diabetes mellitus on the acute as well as long-term regulation of glucose transport into skeletal muscle was investigated. In Paper I, glucose uptake was determined in the perfused hindlimb preparation; in Papers II-VI the glucose transport process was studied independently of glucose metabolism by determining the uptake of the non-metabolizable glucose analogue 3-O-methylglucose into isolated rat epitrochlearis muscles. The main findings are: Acute regulation of muscle glucose transport: 1. Muscle contraction-induced glucose uptake does not require the presence of insulin. 2. Exercise and a maximal insulin stimulus have additive effects on glucose transport. 3. Catecholamines decrease non-insulin-mediated glucose transport in the absence of albumin, whereas in the presence of albumin an enhancement occurs. 4. The effects of catecholamines are abolished during beta adrenergic blockade, but remain unaffected during alpha-adrenergic blockade. Long term regulation of muscle glucose transport: 5. The rat epitrochlearis muscle, a thin, predominantly fast-twitch muscle of the forearm, was shown to be a suitable preparation for the study of factors regulating glucose transport capacity on a long-term basis, since it maintains energy stores and tissue oxygenation for periods of at least 14 h. 6. Sustained insulin deficiency results in marked decreases in basal (40-45%), contraction-induced (50-60%), and insulin-stimulated (65-70%) glucose transport into rat epitrochlearis muscle. 7. The decreased contraction-induced glucose transport capacity can be prevented by frequent exercise during the period of insulin deficiency. 8. The decreased insulin responsiveness of the muscle glucose transport system can be reversed either by treating previously untreated diabetic rats with insulin or by in vitro incubation of the muscles for 12-14 hours. 9. The in vitro normalization of the insulin-stimulated glucose transport capacity (a) does not require the presence of serum or insulin, (b) occurs despite high (30 mM) concentrations of glucose, (c) is incomplete in the presence of diabetic serum and (d) is blocked to the amount of 30-80% in the presence of protein synthesis inhibition. On the basis of these findings, the following is concluded: Muscle contraction can activate the glucose transport system independently of insulin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2890260 TI - Neuropeptide Y and noradrenaline mechanisms in relation to reserpine induced impairment of sympathetic neurotransmission in the cat spleen. AB - The mechanisms underlying the reserpine-induced impairment of the functional responses to sympathetic nerve stimulation and output of noradrenaline (NA) and neuropeptide Y (NPY)-like immunoreactivity (-LI) were studied using the isolated blood-perfused cat spleen. Splenic nerve stimulation (10 Hz for 2 min) during control conditions caused perfusion-pressure increase, volume reduction and an increased output of NA and NPY-LI. After administration of phenoxybenzamine, the nerve stimulation-induced perfusion-pressure increase was almost abolished, the volume reduction inhibited and the output of NPY-LI enhanced. After subsequent addition of propranolol, a clear-cut increase in perfusion pressure upon nerve stimulation reappeared. Local infusion of NPY caused a potent, long-lasting, adrenoceptor-resistant increase in perfusion pressure and a relatively smaller volume reduction of the spleen. Twenty-four hours after reserpine pretreatment (1 mg kg-1 i.v.), which depleted the splenic content of NA greater than 95% and NPY LI by about 50%, the functional responses upon nerve stimulation were markedly reduced. Preganglionic denervation or pretreatment with the ganglionic-blocking agent chlorisondamine did not influence the NA depletion after reserpine treatment. A considerable, adrenoceptor antagonist-resistant, long-lasting functional response as well as a markedly enhanced output of NPY-LI then occurred upon nerve stimulation. In conclusion, reserpine treatment combined with interruption of preganglionic impulse flow reveals non-adrenergic, nerve stimulation evoked splenic functional responses which could be mediated by release of a cotransmitter peptide like NPY. PMID- 2890261 TI - Increased motor activity following combined stimulation of B-HT 920-sensitive and D-1 dopamine receptors. PMID- 2890262 TI - Glycogen and glycogen-hydrolysing lysosomal enzyme activity in mouse liver: effects of fasting, adrenoceptor antagonism and insulin-induced hypoglycaemia. AB - Whereas the phosphorolytic breakdown of liver glycogen is known to be of great physiological importance, the functional role of the hydrolytic glycogenolysis in the lysosomal system is less well understood. In the present study the effects of fasting, alpha- and beta-adrenoceptor antagonism and insulin-induced hypoglycaemia on liver lysosomal glycogen-hydrolysing enzyme activity were investigated in mice. In freely fed mice the glycogen-hydrolysing activity (acid amyloglucosidase) was only 50% of the maltose-hydrolysing activity (acid maltase). Starvation for 24 h reduced the acid amyloglucosidase activity by approximately 30% (P less than 0.001), whereas the activities of acid maltase, acid phosphatase and beta-glucuronidase appeared unaffected. N-acetyl-beta-D glucosaminidase activity was moderately (20%; P less than 0.01) enhanced by fasting. Thus, liver lysosomal enzyme activities may change independently of each other during fasting. Further, during short-term hypoglycaemic conditions (45 min) induced by endogenous or exogenous insulin, the activity of liver acid amyloglucosidase was found to be moderately reduced (15-20%). Blockade of alpha- and beta-adrenoceptors by phentolamine and propranolol did not result in any apparent influence on acid amyloglucosidase activity except for the indirect effect exerted by the phentolamine-induced hypoglycaemia. A moderate negative correlation (r = -0.51; P less than 0.001) between total liver glycogen concentration and acid amyloglucosidase activity was observed in a series of 43 freely fed NMRI mice. Our data show that in mouse liver the acid maltase activity predominates over the acid amyloglucosidase activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890263 TI - Beta-adrenoceptor stimulation increases the pH of parotid acinar cells. AB - To characterize the effect of L-norepinephrine on intracellular pH (pHi) in parotid acinar cells, were measured the accumulation of 14C-labelled 5,5 dimethyloxazolidine-2,4-dione ([14C]DMO), in slices of parotid glands from Sprague-Dawley rats. L-Norepinephrine enhanced the [14C]DMO uptake in a concentration-dependent manner with half-maximal effect at about 1 microM and maximum effect at about 1 mM. The half-maximal effect corresponded to an increase in pHi by 0.08 units and was reduced by 2 microM L-propranolol (beta-adrenoceptor antagonist), but was not affected by 2 microM phentolamine (alpha-adrenoceptor antagonist). The results suggest that L-norepinephrine increases intracellular pH in rat parotid acini and that this effect may be mediated by beta-adrenoceptor stimulation. PMID- 2890264 TI - Exercise and mental health. AB - This paper reviews the mood altering properties of exercise and its potential in the prevention and treatment of mental disorders. The role of the brain monoamines, opioid peptides, the sympathetic nervous system, and cognitive behavioural theory as mediating pathways for the psychological benefits of exercise is critically examined. Clinical trials on exercise are reviewed and suggestions are made for future research in this field. PMID- 2890265 TI - Is the dexamethasone suppression test predictive of response to specific antidepressant treatment in major depression? AB - The authors attempt to correlate the response to dexamethasone suppression test (DST) with a clinical response to antidepressant drugs in 68 patients with major depression. Antidepressants that influence noradrenergic or serotonergic transmission with relative different potencies were selected and used in standard doses for 6 weeks. The response was evaluated weekly by raters blind to DST results and to antidepressant medications prescribed. The retrospective analysis failed to correlate DST response with outcome of treatment. Therefore the present results suggest that this laboratory test does not help to identify subgroups of depressed patients responding preferentially to various antidepressant drugs. PMID- 2890266 TI - Brain neurotransmission in panic disorder. AB - For two decades it has been hypothesized that schizophrenia and depression are related to alterations in the activity of specific neurotransmitters in brain; to a great extent, these theories are based on the assumed mode of action of antipsychotic and antidepressant drugs. With the available knowledge of how panic anxiety can be effectively treated (and elicited) with drugs, it is now reasonable to formulate hypotheses also regarding the contribution of central neurotransmitters to the generation of panic. As will be discussed in this brief review, three substances seem to be of particular importance in this context: serotonin, noradrenaline and GABA. In view of this concept, the putative mode of action of the atypical benzodiazepine derivative alprazolam, which in contrast to other benzodiazepines has been attributed effectiveness in the treatment of panic, will also be discussed. PMID- 2890267 TI - The fatty acid composition of Northern-Canadian marine and terrestrial mammals. AB - The low mortality from cardiovascular disease in Greenland Eskimos has been attributed to their consumption of diets rich in omega-3 fatty acids. These fatty acids are found in fish and marine mammal lipids. Whereas the fatty acid composition of several fish species has been documented, information is more limited on the mammals which feature significantly in the diets of many Arctic populations. This study investigated the fatty acid composition of commonly eaten marine mammals, as well as the polar bear and caribou. The tissue fatty acid composition was species-dependent, probably reflecting to some degree differences in feeding habits. The marine mammals and the amphibious polar bear, but not the caribou, contained substantial quantities of long chain omega-3 fatty acids. These studies further document the transfer of omega-3 fatty acids through the food chain to man and suggest that marine mammal and polar bear lipids are significant sources of omega-3 fatty acids. PMID- 2890268 TI - Comparison of hydrochlorothiazide and slow release furosemide as adjuvant therapy to beta-blockers in the treatment of moderate hypertension. AB - Fifty hypertensive patients on beta-blocker therapy with supine blood pressure greater than or equal to 95 mmHg were included in a parallel group, double-blind study for 12 weeks to compare blood pressures, metabolic and adverse effects of additional treatment with diuretics. Hydrochlorothiazide (HCT) 25 mg daily was added to one group and furosemide 30 mg daily in a slow-release preparation, Lasix Retard (LR), to the other. Blood pressure decreased significantly and similarly in both groups from about 155/101 to about 144/95 mmHg (p less than 0.01). Diastolic blood pressure was lowered to less than or equal to 90 mmHg in 29% of the HCT patients and in 59% of the LR patients. Serum potassium decreased significantly from 4.05 mmol/l to 3.62 mmol/l on HCT, while the decrease on LR from 4.13 mmol/l to 4.05 mmol/l was not significant. Serum urate increased significantly, although within the normal range, on HCT. No change in fasting blood glucose or HbA1C was observed in any group. The patients were asked to report 40 different possible side-effects on a visual analogue scale at every visit. The side-effects already observed on beta-blockers did not change consistently on additional therapy with either HCT or LR. Thus, additional treatment with HCT or LR to patients already treated with beta-blockers results in an equal further blood pressure reduction, but in contrast to treatment with HCT, addition of LR does not affect serum potassium concentrations. PMID- 2890269 TI - Serum phosphate increase during short-term beta-adrenoceptor blockade in thyrotoxicosis. AB - We studied the changes in blood plasma electrolytes during acute and short-term treatment with four different beta-adrenergic-blocking agents in 31 patients with hyperthyroidism. Serum phosphate increased during the first four hours and remained elevated after one week both after cardioselective (acebutolol) and non cardioselective (oxprenolol, pindolol and timolol) beta-blockade (p less than 0.05). Albumin decreased after four hours but no change was found after one week. Serum creatinine increased after one week in the acebutolol-treated group, while sodium, potassium and albumin-corrected calcium in serum did not change. The hyperphosphatemic effect may be due to blockade of beta 1-adrenoceptors, since the effect of the cardioselective acebutolol was no less than that of the non cardioselective beta-adrenoceptor blockers. PMID- 2890270 TI - Receptosomes in the arterial smooth muscle cell. PMID- 2890271 TI - Software Survey Section. PMID- 2890273 TI - A possible physiological basis for effectiveness of acupuncture against psychosomatic disorders. AB - Acupuncture and Oriental meditation, particularly of Zen Buddhists have essential features in common. The physiological correlates of these features are discussed as they apply to therapy of psychosomatic disorders. Both acupuncture and meditation are characterized by alpha rhythms of the encephalograms, by relaxed wakefulness, by analgesia, by their pervasion of virtually the entire body. This set of correspondences is taken as sufficient to postulate that acupuncture induces a stillness with properties similar to those of the "quiet" of meditation. This induced deep relaxation may account for the vasolidation and increased vascular-capillary flow, intrinsic in acupuncture. Among the shared properties are the presence of low physiological noise-level and unresponsiveness to the aversive components of conditioned stimuli. PMID- 2890272 TI - Successful treatment of itching and atopic eczema by transcutaneous nerve stimulation. AB - Low-frequency (2 Hz) transcutaneous electrical nerve stimulation (TNS) may produce prolonged and widespread sympatho-inhibition resulting in improved skin microcirculation with increased skin temperature in patients with peripheral vascular insufficiency. The method has previously been used successfully to improve peripheral circulation in such patients and to accelerate healing of chronic skin ulcers of various etiology. The present report deals with healing of atopic eczema and relief of pruritus by low-frequency TNS treatment in a patient who was followed for 2 years, the first 8 months with daily recordings of the effects, and then for an additional 16 months during which period TNS only occasionally was used. TNS also produced increased plasma levels of ACTH, cortisol and vasoactive intestinal polypeptides (VIP). The mechanisms of the favourable clinical effects are discussed. PMID- 2890274 TI - Long-term treatment of chronic pain with acupuncture. Part II. AB - A 5-year trial of acupuncture therapy in the Finnish NHS is surveyed. The material of 348 pain patients has been described in Part I. Acupuncture was less effective in the elderly, in patients with a psychiatric history, on high doses of analgesics, and in those with longstanding pain. Twenty six per cent of the patients were relieved of pain for more than two years. The response to treatment was not influenced by the patients social status or his expectations of benefit. PMID- 2890275 TI - Interrelationships between the heart and central nervous system: localization of neuro-transmitters and imaging of their associated nuclei, including the raphe nuclei & the locus coeruleus, as well as the imaging of the heart and its representation areas in slices of the human central nervous system using the "Bi Digital O-Ring Test" imaging method. AB - Using microscopic slides of specific tissues from the human body or pure substances including neuro-transmitters such as serotonin, dopamine, norepinephrine, etc., as reference control substances in the Bi-Digital O-Ring Test Molecular Identification Method, the author was able to localize and image normal and abnormal internal organs, and to localize and trace the distribution of neurotransmitters in the different parts of the central nervous system. Using microscopic slides of different parts of the heart, we were able to image the outline of the heart as well as the SA node, AV node, tricuspid valve, mitral valve, aortic valve, pulmonary valve, coronary arteries, and aorta and its branches, including the vertebral arteries, without using any bulky or expensive imaging instruments. Using serotonin as a reference control substance on the different parts of the central nervous system, it was possible to demonstrate the 6 well-known raphe nuclei and the locus coeruleus (which contains serotonin & norepinephrine), as well as the distribution of serotonin in the cerebrum and the cerebellum, all of which closely resembled previously published well-known neuroanatomical structures and distributions of neurotransmitters. As an extension of this work, possible representations of different internal organs on the central nervous system were examined using microscopic slides of different internal organs as reference control substances. The results indicated that the entire heart is represented primarily in the medulla oblongata, and that the SA node and the upper half of the left atrium are represented in the caudal end of the pons; the right side of the heart (i.e. R-atrium, AV node, tricuspid valve, R ventricle) is represented on the right side of the medulla oblongata, and the left side of the heart (i.e. lower half of the L-atrium, mitral valve, L ventricle) is represented on the left side of the medulla oblongata, and the upper half of the left atrium is represented in the caudal end of the left side of the pons. The bottoms of the ventricles are located near the spinal cord. Furthermore, the right and the left sides of the heart are represented in specific areas of each side of the right and left hemispheres of the cerebral cortex, and there are connecting pathways between the representation areas of identical parts of the heart, through the corpus callosum and other neuro pathways. PMID- 2890276 TI - Hypoalgesic effect of laser photobiostimulation shown by rat tail flick test. AB - We demonstrated a 50% increase in pain threshold following laser photobiostimulation (LPBS), employing rat tail-flick test. Helium-neon laser (1 mW) of three different pulsing frequencies (4, 60, and 200 Hz) was applied on tail low resistance point for 15 seconds and tail-flick latencies were measured 30 minutes, 1 hour, 24 hours, 48 hours and 7 days later. LPBS of 4 Hz produced hypoalgesia of rapid onset and short duration while the response to 60 Hz was delayed and lasted longer. LPBS of 200 Hz did not produce any hypoalgesia. PMID- 2890277 TI - The use of cell markers in the study of human hematopoietic neoplasia. PMID- 2890278 TI - New classes of tumor promoters: teleocidin, aplysiatoxin, and palytoxin. PMID- 2890279 TI - Studies on biomodulators of glucocorticoid actions; the nature and the modes of actions of glucocorticoid potency amplifiers. AB - We have found many compounds that amplify the action of glucocorticoid without themselves having any glucocorticoid-like action and have proposed the concept of 'Glucocorticoid Action Biomodulators'. These biomodulators consist of 'Glucorticoid Sensitivity Amplifiers', which greatly amplify the action of glucocorticoid at doses of glucocorticoid that alone have minimal effects, and 'Glucocorticoid Potency Amplifiers', which markedly enhance the effect of glucocorticoid at doses that have maximal effects. Potent activators of protein kinase C, such as 1,2-racemic dioctanoylglycerol, 12-o-tetradecanoyl-phorbol-13 acetate, and epidermal growth factor (EGF), markedly enhanced the induction of tyrosine aminotransferase and ornithine decarboxylase by dexamethasone in adrenalectomized rats in vivo and in primary cultures of adult rat hepatocytes in vitro. They amplified enzyme induction by even a large amount of dexamethasone that had a maximal effect, but had no effect in the absence of glucocorticoid. These modes of amplification show that these compounds are 'Glucocorticoid Potency Amplifiers'. They amplified not only enzyme induction in liver but also growth inhibition by glucocorticoid of solid tumor L5178Y lymphoblasts. They specifically amplified the actions of glucocorticoids and did not amplify the actions of other steroids, such as 17-beta estradiol, glucagon and insulin. The induction of tyrosine aminotransferase by glucocorticoid and its amplification by EGF were both inhibited by 1-(5-iso-quinoline-sulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, and not by N-[2-(methylamino)-ethyl]-5 isoquinoline-sulfonamide, an inhibitor of cyclic nucleotide dependent protein kinases, suggesting that the induction and the amplification are mediated by protein kinase C. PMID- 2890280 TI - Leukotriene C4 metabolism by hepatoma cells and liver. AB - The metabolism of the glutathionyl leukotriene LTC4 in the mercapturic acid pathway was studied in suspensions of AS-30D hepatoma cells and hepatocytes, as well as in vivo in the bile duct-cannulated rat and in primates. 1. Isolated hepatocytes actively took up cysteinyl leukotrienes and metabolized LTC4 not only to LTD4 and LTE4 but also to N-acetyl-LTE4 and to metabolites more polar than LTC4. 2. AS-30D hepatoma cells are deficient in the transport system for the uptake of cysteinyl leukotrienes. Peptide cleavage of LTC4 to LTD4 and LTE4 was catalyzed by ectoenzymes of these cells. Inactivation of gamma glutamyltransferase by acivicin and inhibition of LTD4 dipeptidase by penicillamine largely prevented further catabolism of LTC4 and LTD4, respectively. 3. [3H]LTC4 injected i.v. into rats was rapidly eliminated from the circulating blood, taken up by the liver, and excreted into bile where 77% of the administered radioactivity was recovered within 1 hr. The biliary LTC4 metabolites included LTD4, N-acetyl-LTE4, and metabolites more polar than LTC4. 4. Inhibition of [3H]LTC4 metabolism in vivo by i.v. penicillamine shifted the pattern of biliary cysteinyl leukotrienes; an extended half-life of [3H]LTD4 was associated with a retarded formation of N-acetyl-LTE4 and of polar metabolites. 5. Endogenous cysteinyl leukotrienes elicited by trauma were measured after HPLC separation by radioimmunologic analysis in plasma and bile of rats. The biliary concentration of these leukotrienes was up to 100 times as great as in plasma. N Acetyl-LTE4 was the predominant endogenous metabolite in rat bile. 6. In the monkey Macaca fascicularis, cysteinyl leukotrienes were predominantly eliminated from blood via the liver into bile; renal excretion amounted to about 50% of the hepatobiliary elimination. Absorption of cysteinyl leukotrienes from the intestine resulted in enterohepatic circulation of these mediators. 7. Metabolites of [3H]LTC4 injected i.v. in the monkey were analyzed in bile and urine. In addition to polar metabolites and a small percentage of [3H]LTD4, [3H]LTE4 was a predominant metabolite particularly in bile. LTE4 was also the major endogenous cysteinyl leukotriene detected by radioimmunologic analysis in monkey bile. 8. LTE4 was the predominant endogenous cysteinyl leukotriene measured in human bile in patients suffering from acute pancreatitis. The detected amounts of LTE4 may be sufficient to induce known phenomena associated with acute pancreatitis including the shock-like reaction. PMID- 2890282 TI - Parasite behaviour: understanding platyhelminth responses. PMID- 2890281 TI - Interaction of adrenal and pancreatic hormones in the control of hepatic enzymes during development. AB - In the liver of suckling rats, the synthesis of hepatic tyrosine aminotransferase, serine dehydratase, and phosphofructokinase 2 as well as of renal beta-glucosidase is controlled by the circulating concentrations of adrenal and pancreatic hormones. Glucagon is capable of stimulating enzyme synthesis only in the presence of a steroid hormone. Dexamethasone and estradiol have been found to exert a permissive function on the inducibility of the studied enzymes by glucagon. Between the hormones of the adrenal medulla and glucagon antagonistic effects in enzyme induction were observed. Obviously, this antagonism is mediated by the alpha 1-adrenergic signal transferring system. A characteristic age dependence of enzyme induction by dexamethasone has been established. This might be correlated to alterations in the degree of methylation of the respective promoters. The methylation inhibitor 5-azacytidine influences significantly the enzyme induction by glucocorticoid hormones. PMID- 2890283 TI - PGE binding in isolated hepatocytes: regulation during fasting. PMID- 2890284 TI - Chick retina generates platelet-activating factor. PMID- 2890285 TI - Alpha-linolenic acid deficiency in man: effect of essential fatty acids on fatty acid composition. AB - Alpha-linolenic acid deficiency (ALAD) is described in five adults receiving long term gastric tube feeding with a commercially available powdered formula mixed with water and/or skimmed milk. Three patients receiving the same powder mixed with whole milk showed no signs of essential fatty acid deficiency (EFAD). The patients showed scaly dermatitis and skin atrophy. In four patients, supplementing with cod liver oil and soya oil for 4 weeks normalized n-3 acids in plasma and red cells, while n-6 acids remained unchanged or decreased slightly. At the same time, skin changes were normalized. In the fifth patient, supplementing with ethyl linolenate started to normalize skin changes within 5 days, and after 2 weeks had increased the red cell concentration of 22:6n-3 threefold. Simultaneously, 20:4n-6 increased twofold, to above control level. Minimal daily requirement of alpha-linolenic acid and of long-chain n-3 acids is estimated to be 0.2% to 0.4% and 0.1% to 0.2% of calories, respectively. PMID- 2890286 TI - Sulfasalazine and its anti-inflammatory metabolite, 5-aminosalicylic acid: effect on arachidonic acid metabolism in human neutrophils, and free radical scavenging. PMID- 2890287 TI - A study of cryptorchidism. III: The histochemistry of complex carbohydrates in the testes of cryptorchid patients. AB - The complex carbohydrates in the undescended and contralateral scrotal testes of patients with cryptorchidism, were examined by light microscopic histochemical methods, in comparison with those of normal testes. In the undescended testes, histochemical reactions for acidic and neutral complex carbohydrates were apparently weaker than in the normal testes, especially pronounced in the seminiferous tubular walls. In the germinal and supporting cells of the undescended testes, the amount of galactose residues in the complex carbohydrates decreased from the prepubertal to post-pubertal periods. Periodic acid-Schiff reaction also revealed a decrease in the glycogen content in the germinal and supporting cells of the undescended testes from pre-pubertal to post-pubertal periods. PMID- 2890288 TI - Mammogram interpretation by physician assistants. AB - The objective of this study was to determine whether a health maintenance organization (HMO) desirous of providing low-cost, quality mammography could employ physician assistants (PAs) to interpret mammograms under the supervision of HMO radiologists. After intensive training in mammographic interpretation, four PAs individually interpreted 727 mammograms of 470 normal breasts, 75 breasts with benign breast masses, and 182 breasts with cancer. The interpretations by the PAs were more sensitive and as specific as those made by six HMO radiologists who interpreted the same cases, and as effective as those by radiologists described in the literature. In receiver-operating-characteristic curve analysis, the areas under curves for PAs were larger than those under curves for radiologists. Interpretations by PAs took less time and cost less than did those by radiologists; the dispositions recommended by PAs were similar to those recommended by radiologists. We conclude that properly trained, evaluated, and supervised PAs can interpret mammograms. Legal, practical, and ethical considerations dictate that this can best be accomplished under the direction of radiologists who are well trained in mammography. PMID- 2890289 TI - Drug therapy in the elderly: effects on mental status. AB - Persons over age 65 receive 25 to 30 percent of all drug prescriptions. Since the elderly often require numerous medications for multiple medical problems, the opportunity for deleterious drug interactions is increased. Overmedication, coupled with the older patient's susceptibility to drug toxicity, increases the risk of poor compliance and behavioral disturbances. PMID- 2890291 TI - Electrophysiologic effects of cigarette smoking in patients with and without chronic beta-blocker therapy. AB - After refraining from smoking for at least 8 hours, 22 adult male habitual smokers underwent baseline electrophysiologic study including atrial and ventricular burst pacing and programmed premature stimulation with single extrastimuli. After smoking 2 of their usual brand of cigarettes in rapid succession, the electrophysiologic protocol was repeated. Nicotine, catecholamine and carbon monoxide concentrations all increased significantly. Smoking increased heart rate and improved atrioventricular conduction in the 13 patients receiving chronic beta-blocker therapy (mostly for angina pectoris); increases in heart rate and improvement in atrioventricular conduction were not different statistically from those seen in patients not receiving beta-blocker therapy, suggesting the possibility of a direct effect of nicotine or other components of tobacco smoke. Ventricular refractoriness was not altered and atrial and ventricular arrhythmias were not increased by smoking. Persistent sympathomimetic actions of cigarette smoking may explain in part the failure of beta-blocking drugs to reduce cardiac mortality risk in smokers after myocardial infarction. PMID- 2890290 TI - Electropharmacology of flestolol for supraventricular tachycardia without associated structural heart disease. AB - Flestolol is an ultrashort-acting beta-blocking drug with a half-life of 6.9 minutes. Its antiarrhythmic efficacy was studied in 21 patients with spontaneous and inducible supraventricular tachycardia: atrioventricular (AV) nodal tachycardia in 6 patients and orthodromic AV reciprocating tachycardia in 15. It increased the effective refractory period of the AV node in all patients with AV nodal tachycardia (fast pathway, p less than 0.02; slow pathway, p less than 0.01), but did not alter the anterograde (n = 8) or retrograde (n = 9) refractory periods of accessory pathways. Flestolol prevented initiation of tachycardia by causing block in anterograde AV nodal conduction. It was more effective in patients with AV nodal tachycardia (5 of 6) than in those with AV reciprocating tachycardia (4 of 15, p less than 0.03). In patients in whom it was ineffective, the mean tachycardia cycle length increased by 54 ms because of an increase in AH interval (p less than 0.0001, n = 11). The cycle length of tachycardia induced 30 minutes after infusion was similar to the cycle length in the control state (354 vs 355 ms, n = 16). Flestolol's kinetics permitted clinically indicated electropharmacologic testing of a second antiarrhythmic drug in 8 patients and control of ventricular rate until arrhythmia surgery in 1 patient with incessant tachycardia. No hypotension or toxicity occurred. Our findings indicate that flestolol's principal antiarrhythmic effects are on the AV node, similar to the effects of other beta-blocking drugs. Its ultrashort duration of action is an advantage during electropharmacologic testing. PMID- 2890292 TI - Efficacy of bucindolol in systemic hypertension. AB - The hemodynamic effects of oral bucindolol, a non-selective beta-adrenergic blocking agent with intrinsic sympathomimetic activity and direct vasodilating properties, were studied at rest and during handgrip exercise with a flotation directed pulmonary artery catheter in 12 patients with mild to moderate essential hypertension. After the initial dose of 150 mg of bucindolol, blood pressure (BP) was significantly reduced and cardiac output was increased (from 5.9 +/- 0.8 to 6.8 +/- 1.6 liters/min) in the supine position and during exercise (p less than 0.05). Systemic vascular resistance was reduced (from 1,555 +/- 339 to 1,311 +/- 467 dynes s cm-5, p less than 0.01) at rest and without significant changes during exercise. There were increases in heart rate (13 +/- 13%, p less than 0.01) and right atrial (69 +/- 77%, p less than 0.05), pulmonary arterial (38 +/- 24 %, p less than 0.001) and pulmonary artery wedge pressures (62 +/- 46%, p less than 0.001) during exercise. Bucindolol did not change these variables at rest or during exercise. Bucindolol increased plasma norepinephrine levels both at rest (from 330 +/- 151 to 588 +/- 320 ng/liter, p less than 0.01) and during exercise (from 468 +/- 220 to 685 +/- 390 ng/liter, p less than 0.05). After 4 weeks of bucindolol with doses of 50 to 200 mg 3 times daily, BP was reduced in both supine and standing positions (mean arterial BP of 11 +/- 7% [p less than 0.001] and 11 +/- 6% [p less than 0.001], respectively), without changes in cardiac output, systemic vascular resistance or plasma norepinephrine level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890293 TI - Carrier detection in the hemophilias. AB - The subject of carrier detection in the hemophilias has received new impetus in the past several years. Treatment complications arising from clotting factor concentrates have become more evident and earlier prenatal diagnosis and new genetic markers for the clotting factor genes have focused interest on this area. Until now, carrier diagnosis has relied upon standard pedigree analysis and clotting factor assays. The results obtained using these methods are probabilistic, and the coagulation tests are unavoidably influenced by the effects of random X chromosome inactivation and the inherent variability of the methods involved. With the cloning and characterization of both factor IX and factor VIII genes, has come the capability of using gene analysis to diagnose the carrier state. This usually involves the detection of restriction fragment length polymorphisms (RFLPs) and their use as linked markers for the defective clotting factor gene. In hemophilia A, the combined use of three intragenic RFLPs and two closely linked, highly polymorphic extragenic markers will make carrier information available to approximately 90% of kindred. In hemophilia B, phenotypic analysis has been complicated by the more heterogeneous expression of the gene defect. To date, five intragenic and one closely linked RFLP have been reported, as well as two protein polymorphisms detectable by monoclonal antibody immunoassays. With the combined use of these genetic markers it is likely that accurate carrier assignment will be available to more than 80% of hemophilia B families. PMID- 2890294 TI - A controlled study of Tourette syndrome. I. Attention-deficit disorder, learning disorders, and school problems. AB - Tourette syndrome (TS) is a common, hereditary, neurobehavioral disorder of childhood. To determine the frequency of various behavioral manifestations, we have compared 47 random normal controls to 246 patients with TS, 17 with attention-deficit disorder (ADD), and 15 with ADD secondary to a TS gene (ADD 2(0) TS). All subjects were examined prospectively with a 425-item questionnaire based on the Diagnostic Interview Schedule and the Diagnostic and Statistical Manual of Mental Disorders (DSM III). The TS patients were divided into grade 1 (too mild to treat [17.5%]), grade 2 (requiring treatment [58.9%]), and grade 3 (severe [23.6%]). Patients in all three grades of TS were significantly different from controls for DSM III symptoms of inattention, impulsivity, and hyperactivity. Sixty-two percent of TS patients had ADD, compared with 6.3% of controls; and 48.8% had ADD with hyperactivity (ADDH), compared with 4.2% of controls. In the majority of TS patients, the natural history of the disease was to start with ADDH and 2.4 years later develop motor and vocal tics. Among TS patients, 39% had previously received medication for ADDH or behavior problems, compared with 2% of the controls. Although stimulants can occasionally exacerbate tics, there was no evidence that stimulants cause TS and they are often a valuable adjunct to the treatment of TS. It is estimated that 10%-30% of ADDH is due to or associated with the presence of a TS gene. TS patients had a significantly increased frequency of (1) attending classes for the educationally handicapped, (2) placement in classes for the severely emotionally disturbed, (3) attending any special classes, (4) severe test anxiety, (5) stuttering, (6) letter, number, or word reversal, (7) reading very slowly, and (8) poor retention of material read. A reading-problem score (dyslexia) greater than or equal to 3 was present in 26.8% of TS patients, compared with 4.2% of controls. Number reversal, word reversal, and poor retention were significant even for the TS patients with tics too mild to treat. The multiple ways in which TS impacts school performance, as well as potential remedies, are discussed. PMID- 2890296 TI - DNA restriction-site polymorphisms associated with the alpha 1-antitrypsin gene. AB - Restriction-site variation in and around the alpha 1-antitrypsin gene has been studied using two genomic probes. With use of restriction enzymes SstI, MspI, and AvaII, three polymorphic sites have been described with a 4.6-kb probe in the 5' portion of the gene. With use of a 6.5-kb probe, polymorphisms in the coding and 3' regions of the gene have been detected with AvaII, MaeIII, and TaqI. All of these polymorphisms are of sufficiently high frequency to be useful in genetic mapping studies. The polymorphisms with AvaII and MaeIII (6.5-kb probe) are particularly useful for prenatal diagnosis. PI types and M subtypes tend to be associated with specific DNA haplotypes; there are two different types of DNA haplotypes associated with PI M1. The extent of linkage disequilibrium differs throughout the region of the alpha 1-antitrypsin gene. PMID- 2890295 TI - Development of a single probe for documentation of chimerism following bone marrow transplantation. AB - Although numerous genetic markers are available for studying chimerism after bone marrow transplantation (BMT), there remains a need for a practical and highly informative method that is applicable in the early posttransplantation period. Using DNA restriction-fragment-length polymorphisms (RFLPs), we have evaluated the feasibility of developing a single synthetic oligonucleotide probe to study post-BMT chimerism. We have thus tested three candidate probes, termed O-3315-32, O-3315-80, and O-AY-29, that are homologous to tandemly repetitive sequences. Our results demonstrated donor-specific and recipient-specific fragments in 11 of 11 HLA-matched sibling pairs tested using probes O-3315-32 and O-3315-80. When probe O-AY-29 was used, 14 of 17 sibling pairs showed both donor and recipient markers, one had only a recipient marker, and two were identical. We showed that each of the three synthetic probes was effective in documenting donor marrow engraftment, mixed hematopoietic chimerism, the patient's pre-BMT phenotype (by using cultured skin fibroblasts obtained after BMT), and the origin of the malignant hematopoietic cells (i.e., of donor or recipient origin) in patients who developed recurrent hematologic malignancy following BMT. Compared with the use of cloned genomic probes, there are several important advantages to the use of synthetic oligonucleotide probes in studying post-BMT chimerism. Synthetic probes have absolute hybridization specificity and can be designed to suit the purposes of an individual study, since they have adjustable specificity that can be altered by changes in the length of the probe and by changes in the hybridization temperature. A single synthetic probe analogous to several highly polymorphic loci can have a polymorphism information content sufficiently high so that all but a small percentage of BMT patients could be followed easily; for example, if a probe were complementary to three highly polymorphic unlinked loci, it would discriminate approximately 98% of sibling donor/recipient pairs. This would be accomplished using only one restriction-endonuclease digestion and only one gel electrophoresis. Since other genetic markers, e.g., red blood cell antigens, immunoglobulin allotypes, and chromosome analysis, are not uniformly informative and, in some cases, cannot be used in the early posttransplantation period, the use of synthetic oligonucleotide probes for analysis of DNA RFLP is emerging as the method of choice for studies of post-BMT chimerism. This method will allow for the development of new knowledge that has not been possible with previous methods. PMID- 2890297 TI - Linkage of DNA probe B79a (D7S13) to cystic fibrosis. AB - We have conducted, in 64 affected families, a study of linkage between the anonymous DNA segment pB79a (D7S13) and the locus for cystic fibrosis (CF) on chromosome 7q. The maximum lod score was 12.60 at theta = .08 (confidence bounds .045-.135). Although D7S13 is not sufficiently close to CF for routine use in DNA based prenatal diagnosis, it will be helpful in certain families when other nearby markers are uninformative. D7S13 will also be useful for refining the linkage map of the CF region. PMID- 2890298 TI - Neutrality tests of highly polymorphic restriction-fragment-length polymorphisms. AB - The allele frequency data of Baird et al. were tested using Ewens-Watterson sampling theory for goodness of fit to the infinite-alleles model of neutral evolution. Although probes of both the HRAS-1 and D14S1 loci identify highly diverse restriction-fragment-length polymorphisms, the observed values of gene identity (F) and the common allele frequency (C) are not significantly different from the neutral expectation. Allele frequency distributions show a tendency toward a deficit in diversity for HRAS-1 and a slight excess diversity for D14S1. The direction of these departures is consistent with potential selective effects of the Harvey-ras oncogene and hitchhiking of the D14S1 locus to closely linked immunoglobulin genes. Direct chi 2-tests of goodness of fit of the observed and expected allele frequency distributions reveal significant departures in the caucasoid and Hispanic HRAS-1 distributions but not in any of the other tests. PMID- 2890299 TI - Understanding the use of behavioral rating scales in studies evaluating the efficacy of antianxiety and antidepressant drugs. AB - Behavioral rating scales commonly used in efficacy studies of antianxiety and antidepressant drugs are described, and the appropriate use of these scales in clinical studies is discussed from the perspective of pharmacists who must evaluate such studies. Defined first are four attributes by which all rating scales are developed and evaluated: standardization, normalization, validity, and reliability. In psychopharmacology research, rating scales are used to select subjects for study, assess the severity of an illness, measure change in behavior over time, and determine treatment efficacy. Four types of rating scales (patient self-assessment, interview-based, ward-observation, and assessment by significant others) are defined. Some of the most commonly used behavioral rating scales are classified and described; their individual advantages and limitations are evaluated. Knowledge of the characteristics of the various behavioral rating scales is essential to understanding how they can be used most appropriately in drug-efficacy studies to measure changes in behavior and mood. PMID- 2890300 TI - Multiple endocrine neoplasia syndrome type 2: the value of screening and central registration. A study of 15 kindreds in The Netherlands. AB - Since 1975, 10 families with the multiple endocrine neoplasia (MEN)-2A syndrome and five with the MEN-2B syndrome, making a total of 101 patients, have been identified in The Netherlands. Twenty-three of the MEN-2A patients died before the start of the screening program. The average age of the patients whose death was due to pheochromocytoma (n = 11) or medullary thyroid carcinoma (n = 12) was 34.9 and 49.2 years, respectively. Eighty-seven patients with the MEN-2A syndrome and eight with the MEN-2B syndrome underwent thyroidectomy for C-cell hyperplasia and/or medullary thyroid carcinoma. Eighteen patients had signs or symptoms caused by MEN-2A (group A), 60 were relatives of these patients who had been found to be affected at the first screening of the family (group B), and nine relatives had had negative screening results that later became positive (group C). Five patients had signs or symptoms due to MEN-2B (group A) and three were relatives of these patients who had been found to be affected at the initial screening (group B). To assess the effect of screening, we compared these groups with respect to the occurrence of metastatic medullary thyroid carcinoma at thyroidectomy and the results of the postoperative calcitonin tests. Among the MEN-2A families, 72 percent of group A, 33 percent of group B, and none of group C were found to have metastatic medullary thyroid carcinoma at surgery. In the MEN-2B families, all five patients in group A and one of the three patients in group B had metastatic disease. The "cure rates" in these three groups with MEN 2A, as determined by stimulated calcitonin assessment, were 11, 57, and 100 percent, respectively. One of the five patients with MEN-2B in group A and two of the three patients in group B showed normalization of the stimulated calcitonin value after surgery. From these results, it may be concluded that screening can lead to the detection of medullary thyroid carcinoma in an earlier stage, which in turn may permit curative treatment and improvement of both prognosis and life expectancy. The need for supervision of affected families by central registration to promote periodic examination and to guarantee the continuity of such screening is discussed. PMID- 2890301 TI - Hyperventilation and panic disorder. AB - Hyperventilation syndrome and panic disorder are both common, serious, and easily treatable disorders. The similarity of their symptoms and physiology, the demonstration of hyperventilation during spontaneous and laboratory-induced panic episodes, provocation of panic-like symptoms in some patients with panic disorder using hyperventilation, the importance of psychologic factors in producing hyperventilation, and successful treatment of panic disorder with breathing retraining all indicate a strong association between these two conditions. About 50 percent of patients in each group show evidence of both disorders. It is suggested that many patients in each group show evidence of both disorders. It is suggested that many patients with either diagnosis have the same disorder and share a biologically and often genetically determined hypersensitivity of a central "alarm" system. Panic and hyperventilation provoked by inappropriate activation of this system are postulated to reinforce each other by a positive feedback loop. Treatments directed at any part of this loop are likely to be successful. Clinical implications of the link between these conditions are discussed. PMID- 2890302 TI - A lymphoproliferative disorder caused by human T-lymphotropic virus type I. Demonstration of a continuum between acute and chronic adult T-cell leukemia/lymphoma. AB - A 35-year-old black man is described who had a human T-lymphotropic virus type I (HTLV-I) infection while living in a non-endemic region. A lymphoproliferative disorder developed that might be considered as a transition stage between acute and chronic adult T-cell leukemia/lymphoma. This suggests that HTLV-I-induced neoplasias represent a continuous disease spectrum. PMID- 2890303 TI - Close linkage of the Wieacker-Wolff syndrome to the DNA segment DXYS1 in proximal Xq. AB - Linkage studies with RFLPs were performed in a large family in which the Wieacker Wolff syndrome is segregating. In this new syndrome (McKusick, 1986, No. 31458) patients have congenital contractures, progressive neuropathic muscle atrophy, involving also some cranial nerves with oculomotor apraxia and dyspraxia of the face and tongue muscles, and mental retardation. This is an X-linked recessive syndrome. We found close linkage between the syndrome locus and the DNA segment DXYS1 (z = 3.225 at theta = 0.0) in proximal Xq. PMID- 2890304 TI - Increased tubular enzyme excretion in preeclampsia. AB - The pathophysiology of preeclampsia includes ischemia and microinfarctions of the kidney, which could induce renal tubular cells to release enzymes into urine. We therefore measured the concentrations of two markers of renal tubular damage, N acetyl-beta-D-glucosaminidase and alanine aminopeptidase, in urine specimens from women with mild or severe preeclampsia and compared the results with those from healthy pregnant and nonpregnant women. The median urinary concentrations of N acetyl-beta-D-glucosaminidase and alanine aminopeptidase in women without preeclampsia increased progressively through the first, second, and third trimesters and reached maximum values of 1.12 and 0.77 U/mmol creatinine, respectively. Median concentrations of the two enzymes were significantly higher in women with mild preeclampsia (N-acetyl-beta-D-glucosaminidase = 1.40, alanine aminopeptidase = 1.12 U/mmol creatinine) or severe preeclampsia (N-acetyl-beta-D glucosaminidase = 2.90, alanine aminopeptidase = 1.26 U/mmol creatinine). This increased enzyme excretion indicates subclinical preeclamptic renal tubular damage. PMID- 2890305 TI - Beta-adrenergic receptor agonist infusion increases plasma prostaglandin F levels in pregnant sheep. AB - Recent evidence of a stimulatory effect of beta-adrenergic receptor agonists on prostaglandin production by human fetal membranes in vitro prompted us to investigate whether prostaglandins are increased during beta-agonist infusion in vivo. On days 120 to 125 of gestation, blood samples were drawn from the aorta and vena cava of five crossbred ewes at 15-minute intervals for 1 hour before, during, and for 1 hour after a 3-hour infusion of isoproterenol (0.16 microgram/kg/min) or normal saline solution. Plasma prostaglandin F2 alpha levels increased (177% +/- 13% SEM over baseline; p less than 0.002) in maternal aorta, while plasma 13,14-dihydro-15-keto prostaglandin F2 alpha levels increased in both aorta and vena cava (354% +/- 47% and 309% +/- 75% over baseline, respectively; p less than 0.002) during isoproterenol infusion but not during saline solution infusion. No change was seen in plasma prostaglandin E2 levels. The increase in plasma stimulatory prostaglandins in the pregnant ewe during beta agonist infusion is compatible with the increased uterine activity observed after myometrial desensitization by continuous beta-agonist infusion. PMID- 2890306 TI - Effects of cigarette smoke exposure on retention of asbestos fibers in various morphologic compartments of the guinea pig lung. AB - For investigation of mechanisms whereby smoking might potentiate asbestos-related disease, guinea pigs were given 0.5 mg UICC amosite by intratracheal instillation. Half the animals were subsequently exposed to cigarette smoke. Animals were sacrificed at 1 day, 7 days, and 1 month after exposure. Lungs were lavaged and macrophages separated from the lavage fluid. Lung fiber concentration, numbers of fibers in macrophages, and fiber sizes from tissue (TFs), macrophages (MFs), and macrophage-free lavagate (FFs) were determined by electron microscopy. Smoke-exposed animals retained greater numbers of fibers in lung tissue by 1 month but had greater total numbers of fibers in macrophages at all time periods. In both smokers and nonsmokers, fibers in the three morphologic compartments had distinctly different lengths: the longest fibers were found associated with the lung tissue; the macrophages always contained the shortest fibers; and the macrophage-free lavagate had fibers of intermediate size. However, fiber widths and aspect ratios did not show the same clear separation by anatomic compartment, suggesting that in both smoking and nonsmoking animals length is the size parameter which is most important in determining fiber clearance. Smoking did not affect the lengths of MFs but did produce a progressive reduction in the lengths of FFs and TFs with time. These data indicate that smoking causes a marked increase in the number of fibers retained in the lung within macrophages and suggest that either macrophage removal via the mucociliary escalator or macrophage mobility is impaired by cigarette smoke. However, smoking does not change the sizes of fibers in macrophages and does not appear to depress phagocytic capacity. These observations imply that failure of macrophage clearance and subsequent re-release of fibers into the medium may at least partially explain the changes in fiber sizes and eventual increases in tissue fiber concentrations in smoke-exposed animals. PMID- 2890307 TI - A comparative trial of pharmacologic strategies in schizophrenia. AB - An open comparative trial was conducted involving 42 schizophrenic outpatients randomly assigned to one of two methods of drug administration: continuous medication (N = 21) and targeted medication plus psychosocial intervention (N = 21). The results, which suggest an extensive similarity with respect to outcome for the two treatments over a 2-year period, argue for the continuation of research on the relative effectiveness of the targeted drug approach, particularly in cases judged suitable for drug reduction strategies. PMID- 2890308 TI - Tardive dyskinesia and neuroleptic-induced parkinsonism in Japan. AB - The authors studied neuroleptic drug response in 126 inpatients in Japan. They found similar prevalences and risk factors of tardive dyskinesia and neuroleptic induced parkinsonism in Japan and the West, despite cross-cultural differences in psychiatric practice. PMID- 2890309 TI - Follow-up study of 11 patients with potentially reversible tardive dyskinesia. AB - The authors followed the course of 11 patients with potentially reversible tardive dyskinesia while they were taking minimum effective neuroleptic doses. After 10 years, the symptoms of tardive dyskinesia had disappeared in eight patients, were minimal or questionable in one, and had become persistent in two. PMID- 2890310 TI - Time course of effects of clonidine. PMID- 2890311 TI - The control of intra-ocular pressure during the induction of anaesthesia for emergency eye surgery. A high-dose vecuronium technique. AB - A technique of rapid sequence induction of anaesthesia for use in patients with penetrating eye injuries is described. This utilises a three maximal breaths method of pre-oxygenation, the intravenous injection of thiopentone and high dose vecuronium (0.2 mg/kg). Using the loss of eyelash reflex as the starting point for timing, all patients were intubated after 60 seconds without coughing and bucking. No postintubation increases in intra-ocular pressure were seen in 70% of patients and in no patient did the increase in intra-ocular pressure exceed 5 mmHg. After 3 minutes of apnoea, the minimum haemoglobin oxygen saturation was 94% with a mean value of 97.6%. PMID- 2890312 TI - Prolonged neuromuscular blockade in an infant. PMID- 2890313 TI - Priming with vecuronium in obstetrics. PMID- 2890314 TI - The effects of vecuronium on intra-ocular pressure. AB - The effects of vecuronium on intra-ocular pressure were investigated in doses of 0.1 mg/kg during steady state anaesthesia (n = 5), 0.1 mg/kg as part of a normal sequence induction preceded by thiopentone (n = 10), and 0.15 mg/kg as part of a rapid sequence induction with vecuronium administered prior to thiopentone (n = 10). Administration of vecuronium during steady state anaesthesia was associated with a significant decrease. Vecuronium produced a small reduction in pressure during a normal sequence induction, following a significant reduction after thiopentone. Tracheal intubation during normal sequence and rapid sequence inductions produced increases in pressure above the pre-intubation value (significantly so in the case of normal sequence induction); however, the intra ocular pressure always remained below the pre-induction value, which suggests that vecuronium 0.15 mg/kg is a suitable relaxant as part of a rapid sequence induction technique where the use of suxamethonium is contraindicated. PMID- 2890315 TI - Recurarisation after vecuronium in a patient with renal failure. PMID- 2890316 TI - Quantitation of genes and transcripts by saturation hybridization in urea solutions using strand-selected probes. AB - This report describes methods for quantifying specific sequences in preparations of single-stranded or double-stranded nucleic acids. We use saturating amounts of hybrid-selected, strand-specific probes and perform hybridizations in urea solutions. Hybrids (RNA-DNA or DNA-DNA) are then analyzed by either of two methods. The first employs standard S1 nuclease digestion, precipitation of resistant material on glass fiber filters, and assay by liquid scintillation counting. This method is generally chosen in the assay of rare transcripts in total nucleic acid extracts as well as preparations of polyadenylated RNA. The second employs the separation of excess probe from probe-target hybrids by gel electrophoresis, recovery of hybrids on ion-exchange paper, and determination of cpm bound by liquid scintillation counting. This method is of particular value in the assay of double-stranded sequences and the quantitation of restriction fragment length polymorphisms. Whereas both methods are accurate over ranges of target abundance representing at least several orders of magnitude, the latter ("NA45 assay") is most sensitive, and the selection of M13-bound or unbound DNA fragments by this method can be exploited in a variety of other applications. PMID- 2890317 TI - Separation of DNA restriction fragments by ion-exchange chromatography on FPLC columns Mono P and Mono Q. AB - Separation of DNA restriction fragments by FPLC ion-exchange chromatography on Mono Q and Mono P columns was investigated. The columns were found to be particularly suitable for the separation of fragments up to 500-600 bp long. Larger fragments can also be separated although less effectively. We found the following practical working ranges for the parameters investigated: pH, 4 to 11; flow rate, 0.05 to 0.6 ml/min corresponding to separation times between 2 and 20 h. (better resolution is achieved at lower flow rates); gradient slope; between 0.5 mM eluting salt/ml buffer and over 5 mM/ml (better resolution is achieved at lower gradient slopes; eluting ionic strength was found to be independent of gradient slope); gradient composition, chloride salts of smaller monovalent cations eluted the DNA at lower ionic strengths but separations obtained were similar; additives, substances such as urea, formamide, and EDTA can be added without chromatographic effects; sample amount: amounts from 2.5 to 200 micrograms were applied, corresponding to single peak content of from 42 ng to 74 micrograms DNA. Yields were generally over 90% and the chromatographed DNA was fully accessible to restriction enzyme cleavage. Separations occurred predominantly according to DNA size, but AT-rich fragments were retarded in a predictable way. PMID- 2890318 TI - Neuromuscular interaction of magnesium with succinylcholine-vecuronium sequence in the eclamptic parturient. PMID- 2890319 TI - [Neuromediator activity in the postresuscitation period following severe combined experimental and clinical trauma]. PMID- 2890320 TI - The surgical treatment of the Zollinger-Ellison syndrome: an update. AB - Forty-six professors of surgery in answers to a questionnaire reported that 143 patients with Zollinger-Ellison syndrome had been admitted to their hospitals within the last 2 years. The bed capacity of these hospitals totaled 27,019. In extrapolating these figures, it is seen that the capacity of the 46 institutions averaged 587 beds per hospital, and that an average 71.5 patients with Zollinger Ellison syndrome were admitted each year. In other words, a hospital with 587 beds might expect 1.55 yearly admissions of patients suffering from this disease. Two surgical methods have emerged as today's main treatment choices for Zollinger Ellison syndrome that is unaccompanied by isolated gastrinoma. These are 1) preoperatively administered H2 blockers followed by less-than-total gastrectomy, truncal vagotomy, and postoperative H2-blocker therapy; and 2) preoperatively administered H2 blockers followed by highly selective vagotomy plus postoperative H2-blocker therapy. Only seven of 46 respondents still maintain that total gastrectomy should be carried out to cure the disease. All respondents advocate excision of an isolated gastrinoma as the treatment of choice if one is found at surgery. PMID- 2890321 TI - A combined regimen for the prophylaxis of Curling's ulcer. AB - After severe thermal injury, acute gastroduodenal mucosal lesions occur in up to 80 per cent of patients. Prior to prophylactic antacid therapy, one-third of these lesions progressed to ulceration, which frequently resulted in major life threatening hemorrhage. Antacid treatment regimens have dramatically reduced this complication. However, the incidence of occult complications that result in increased morbidity has remained unchanged. We evaluated prospectively a combined treatment regimen using antacid, an H2-receptor antagonist, and enteral feeding in 60 patients who had serious burns (mean burn size, 36% body surface area) in this series. The incidence of both overt and occult complications was 3 per cent and in no patient did a perforation develop nor was operative intervention required. No patient died of the complications of Curling's ulcer. Combination therapy may be of value in other patients prone to stress ulceration. PMID- 2890322 TI - [Pyoderma gangrenosum: treatment by salazosulfapyridine]. PMID- 2890323 TI - [Human retroviruses. Significance for pediatrics]. PMID- 2890325 TI - [When and how should one operate on primary open-angle glaucoma?]. PMID- 2890324 TI - The concept of coupling blood flow to brain function: revision required? AB - A tight coupling exists between brain function and cerebral perfusion in most situations. The Roy and Sherrington hypothesis has been widely accepted to account for the phenomenon: increased neuronal metabolic activity will give rise to the accumulation of vasoactive catabolites, which decrease vascular resistance and thereby increase blood flow until normal homeostasis is reestablished. However, the hypothesis does not account for the disproportionate increase in flow that occurs in a number of circumstances. There are additional difficulties in reconciling more recent experimental data with the Roy and Sherrington hypothesis. In this review we direct attention toward the rich perivascular nerve supply to all parts of the cerebral circulation as possibly being an alternative control system allowing for rapid parallel changes in flow and neuronal activity. PMID- 2890326 TI - Chautauqua '87--a peak experience. PMID- 2890327 TI - Kinetics of reduction by free flavin semiquinones of algal cytochromes and plastocyanin. AB - It had been shown that plastocyanin and cytochrome c-553 are functionally interchangeable in algae and that the physiological electron transfer reactions are sensitive to ionic strength. The isoelectric points of these proteins range from very acidic to basic depending upon species, and naturally occurring amino acid substitutions of charged residues have been shown to affect the kinetics of electron transfer, presumably through alteration of protein net charge. We have now shown that these naturally occurring amino acid substitutions also affect the kinetics of nonphysiological electron transfer reactions, and that we can quantitate the extent of nonconservation of charge. The reduction of plant and algal proteins by FMN semiquinone is sensitive to ionic strength and the effects can be correlated with net protein charge with regard to sign, but not to magnitude, with the charge at the site of electron transfer varying from +3 through 0 to -3. We had previously observed in a large variety of electron transfer proteins from bacteria (G. Tollin, T. E. Meyer, and M. A. Cusanovich (1986) Biochim. Biophys. Acta 853, 29-41) that charge localized at the site of electron transfer, rather than net protein charge, was more likely to affect kinetics. This also appears to be the case with the algal proteins. By comparison of protein structures, we have been able to predict which substitutions are likely to be responsible for the kinetic effects in the algal proteins and to discuss the implications of such changes for function. PMID- 2890328 TI - The effects of exchange-inert metal-nucleotide complexes on the kinetics of beef heart mitochondrial F1-ATPase. AB - The inhibition of beef heart mitochondrial F1 by exchange-inert metal-nucleotide complexes was examined. Mono- and bidentate Cr(NH3)4ATP were found to be mixed noncompetitive inhibitors of F1-catalyzed ATP hydrolysis (values of Ki = 0.5 and 0.1 mM; values of alpha = 0.2 and 24, respectively). Rh(H2O)nATP was also found to be a mixed noncompetitive inhibitor of F1-catalyzed ATP hydrolysis (Ki = 0.3 mM, alpha = 0.7). These compounds were used in a series of dual inhibition experiments, along with mono- and bidentate CrATP and Co(NH3)4ATP. All the exchange-inert metal-nucleotides examined were found to be mutually exclusive inhibitors of F1, indicating that they all bind to the same site(s). It is postulated that the pKa of the metal-coordinated ligands is related to the potency of inhibition by these compounds. It appears probable that the exchange inert nucleotide complexes are binding to site(s) in addition to the catalytic site(s) of F1. PMID- 2890329 TI - The stereoselectivity of the Clostridium perfringens phospholipase C: hydrolysis of thiophosphate analogs of phosphatidylcholine. AB - Thiophosphate containing analogs of phosphatidylcholine have been synthesized with varying degrees of structural complexity. These analogs have been used in a continuous spectrophotometric assay for phospholipase C from Clostridium perfringens in order to examine the requirement for substrate ester functionalities and the stereoselectivity of the enzyme. The substrate analogs with ester groups in the nonpolar portion of the molecule were acceptable substrates for phospholipase C, while those analogs without ester functionalities were not hydrolyzed. Substrate analogs with chiral centers were resolved using the stereospecificity of phospholipase A2 from Crotalus atrox venom. These resolved substrates were used to study the biphasic hydrolytic time courses observed when rac-dioctanoylphosphatidylthiocholine was used as substrate. The "naturally occurring" enantiomer with R absolute configuration was rapidly hydrolyzed in the presence of phospholipase C while the "nonnaturally occurring" enantiomer with S configuration was slowly hydrolyzed only after a long induction or "lag" period. The selectivity for the R enantiomer over the S enantiomer can be lessened by altering the composition of the substrate micelles resulting in accelerated rates of hydrolysis of the S enantiomer. PMID- 2890330 TI - Isolation and structural studies of the intact scrapie agent protein. AB - Purification of the scrapie agent by methods using digestion with proteinase K yields a protein product, PrP-27-30, with an apparent mass of 27-30 kDa (D. C. Bolton et al. (1982) Science 218, 1309-1311; S. B. Prusiner et al. (1982) Biochemistry 21, 6942-6950). In contrast, a 33-37 kDa glycoprotein, HaSp33-37, was the major protein component isolated from scrapie-affected hamster brain by a procedure that did not use protease digestion. The purified fractions containing HaSp33-37 had greater than 10(11) LD50 units of the scrapie agent per milligram of protein. Proteinase K digestion of HaSp33-37 gave a product indistinguishable from PrP-27-30 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. The amino acid sequence of the first 22 residues of HaSp33-37 was determined. The sequence coincided with that predicted for the N-terminus of the precursor to PrP-27-30 (K. Basler et al. (1986) Cell 46, 417-428; N. K. Robakis et al. (1986) Proc. Natl. Acad. Sci. USA 83, 6377-6381) after processing by signal protease. HaSp33-37 was digested with N alpha-tosyl-L-phenylalanine chloromethyl ketone-trypsin to produce a 29-32 kDa protein fragment; following digestion this fraction retained complete biological activity. The amino terminal sequence of the 29-32 kDa protein corresponded to a position intermediate between the amino termini of HaSp33-37 and PrP-27-30. We conclude that HaSp33-37 is the intact form of the scrapie agent protein and that PrP-27-30 is produced by proteinase K degradation when this enzyme is introduced during isolation of the scrapie agent. PMID- 2890331 TI - Hyperglycemic effect of lidamidine in the rat. AB - Lidamidine, a new antidiarrheal agent, produced a dose-dependent increase in plasma glucose levels in fed rats. The hyperglycemic response was evident 10 min after oral administration of lidamidine and lasted for 4 hr. Lidamidine's effect was absent in alloxanized rats. Insulin administration prevented the hyperglycemia. Pretreatment with the alpha 2-adrenoceptor antagonists yohimbine or RX781094A blocked the hyperglycemic response, while prazosin, propranolol, and hexamethonium pretreatment had no effect. These results indicate that the hyperglycemic effect of lidamidine is primarily due to the activation of peripherally located alpha 2-adrenoceptors that inhibit the release of insulin from pancreatic beta-cells. PMID- 2890332 TI - Evolutionary relationship between Enterobacteriaceae: comparison of the ATP synthases (F1F0) of Escherichia coli and Klebsiella pneumoniae. AB - The ATP synthase complex of Klebsiella pneumoniae (KF1F0) has been purified and characterized. SDS-gel electrophoresis of the purified F1F0 complexes revealed an identical subunit pattern for E. coli (EF1F0) and K. pneumoniae. Antibodies raised against EF1 complex and purified EF0 subunits recognized the corresponding polypeptides of EF1F0 and KF1F0 in immunoblot analysis. Protease digestion of the individual subunits generated an identical cleavage pattern for subunits alpha, beta, gamma, epsilon, a, and c of both enzymes. Only for subunit delta different cleavage products were obtained. The isolated subunit c of both organisms showed only a slight deviation in the amino acid composition. These data suggest that extensive homologies exist in primary and secondary structure of both ATP synthase complexes reflecting a close phylogenetic relationship between the two enterobacteric tribes. PMID- 2890333 TI - [H2-antihistaminics. 36. Isolamtidine and analogs]. PMID- 2890334 TI - Derivatives of 2-amino-1,2,3,4-tetrahydronaphthalene. XI: trans-6,9-dimethoxy 2,3,4a,5,10,10a-hexahydro-4H-naphth[2,3-b]1, 4-oxazines--tricyclic analogs trans 2-amino-3-hydroxy-5,8-dimethoxytetralins. PMID- 2890335 TI - Ether derivatives of 3-amino-1,2-propanediols, VI. Syntheses and pharmacological investigations of 5,8-bis-[2-hydroxy-3-(alkylamino)propoxy]-1,4 dihydronaphthalenes. PMID- 2890336 TI - Analyses of drugs by polarographic methods, XXX: Electrochemical behavior of metaclazepam[7-bromo-5-(2-chlorophenyl)-2,3-dihydro-2-(methoxyme thyl)- 1- methyl 1H-1,4-benzodiazepine] and assay of its formulations. PMID- 2890337 TI - [Morphofunctional state of the APUD-system cells of the lungs in hyaline membrane disease of newborn infants]. AB - Examination of these cells in newborn infants with hyaline membrane disease. (HMD) has demonstrated involvement of neuroendocrine elements in its patho- and morphogenesis. A crucial factor in HMD development is immaturity of the lungs, one sign of which is the presence of numerous serotonin-containing cells. Degranulation of APUD cells and serotonin lease under exposure to pathogenic factors initiate pathologic reactions in the lungs and account for the earliest manifestations of the disease. PMID- 2890338 TI - [Direct myocardial revascularization with the left gastro-epiploic artery. A new alternative to aortocoronary bypass. A case report]. PMID- 2890340 TI - Drug dependence in clinical medicine. PMID- 2890339 TI - Topographic distribution of Thy-1 positive cells in epithelial tissues of BALB/c mice. AB - Epithelial sheets prepared from murine oral epithelia (palate, lining mucosa, gingiva) and oesophagus contained dendritic and round Thy-1 positive (+) cells similar to those observed in epidermis by immunofluorescence microscopy. Bladder, intestine and tracheal epithelium did not contain such cells. Thus, cells bearing the cells-surface glycoprotein Thy-1, like Ia-antigen-bearing Langerhans cells, may be restricted to stratified squamous epithelia. PMID- 2890341 TI - A young woman with malignant hypertension. PMID- 2890342 TI - A survey of management of arrhythmias following myocardial infarction. PMID- 2890343 TI - Brain monoamine concentrations in turkey poults infected with Bordetella avium. AB - Six hours post-hatch, large white turkey poults were inoculated intranasally with 5 X 10(7) organisms of the "W" isolate of Bordetella avium. Three hours after inoculation and subsequently on days 7, 10, 14, 21, and 28 postinoculation, 30 infected and 30 uninfected control poults were injected intramuscularly with alpha methylparatyrosine (AMPT, 250 mg/kg), and an additional 30 of each group received a saline vehicle. Three hours after AMPT injection, whole brains from treated and untreated poults from both infected and control groups were removed, weighed, and frozen until assayed for norepinephrine (NE), dopamine (DA), and serotonin (5-HT). B. avium-infected poults had a significant reduction in steady state NE and Da and a greater depletion of NE and DA after AMPT treatment compared with control poults. Infected poults had significantly reduced whole brain 5-HT concentrations, which persisted through 21 days postinoculation. Altered brain NE, DA, and 5-HT concentrations suggest that the B. avium-infected poults may be less able to cope with additional stressors. PMID- 2890344 TI - A comparison of two methods of training resistance to visually-induced motion sickness. AB - This report concerns the use of two methods of training subjects to tolerate visually-induced motion sickness (VMS). Sixteen subjects were selected on the basis of their response to a motion sickness history questionnaire and assigned to one of four groups on the basis of their ability to tolerate visually-induced motion (VM). One group received 10 sessions of confidence building and desensitization training (BT); a second group received 10 sessions of EMG and temperature biofeedback (FB); a third group received 10 sessions of BT and 10 sessions of FB (BTFB); and a fourth group received no treatment (C). The results indicated that the BT and BTFB groups exhibited significant increases in tolerance to VM when pretreatment measures were compared to posttreatment measures, while no significant differences in pre-post measures were observed in the FB or C groups. A similar pattern emerged from the symptomatology data. PMID- 2890345 TI - Differential effects of competitive benzodiazepine receptor antagonists on the anticonflict activity of Go 4962. AB - The anticonflict activity of the triazolobenzothiadiazine Go 4962 (40 mg/kg po) in the four-plate test using male NMRI mice was selectively antagonized by beta CCE (10 mg/kg iv), but not by Ro 15-1788 (20 mg/kg ip) or CGS 8216 (20 mg/kg ip), although Go 4962 has affinity for the benzodiazepine receptor. In contrast, the anticonflict activity of diazepam (4 mg/kg po) was antagonized by all three BZ antagonists. Relative to known putative anxiolytics, this profile of Go 4962 is unexpected and unique. PMID- 2890346 TI - Proteins of the kidney microvillar membrane. Enzymic and molecular properties of aminopeptidase W. AB - Aminopeptidase W is a newly discovered enzyme of the renal and intestinal brush borders, having been first isolated as a 130 kDa glycoprotein recognized by a monoclonal antibody [Gee & Kenny (1985) Biochem. J. 230, 753-764]. It is particularly effective in the hydrolysis of dipeptides, Glu-Trp (Km 0.57 mM; kcat. 6770 min-1) being a favoured substrate. Dipeptides with tryptophan, phenylalanine or tyrosine in the P1 position were rapidly hydrolysed, but the requirements in respect of the P1 residue were not stringent. The activity of aminopeptidase W is markedly influenced by ionic conditions. The highest activity was observed in 100 mM-Tris/HCl, pH 8; phosphate ions were strongly inhibitory. Activity was also greatly affected by bivalent metal ions, and the magnitude and direction of the effects depended on the nature of the buffer anions and on pH. The most effective inhibitors were amastatin and bestatin. Some thiols also inhibited, but other chelating agents, EDTA and 1,10-phenanthroline, had no effect over the concentration range 1-10 mM. Other group-specific inhibitors, for cysteine, serine or aspartic peptidases, were also ineffective. Some molecular properties were studied. Deglycosylation by treatment with N-glycanase diminished the apparent subunit Mr from 130,000 to 90,000. The enzyme contained zinc, 1.2 atoms/subunit, and in spite of the atypical properties of this enzyme in respect of chelating agents, a zinc-catalysed mechanism is the most probable. Its roles in digestion and in renal function are not yet clear. PMID- 2890347 TI - Bradykinin action in the rat duodenum: receptor binding and influence on the cyclic AMP system. AB - Bradykinin binds to a single class of binding sites at rat duodenum plasma membranes. In the presence of endogenous calcium and at low bradykinin concentrations the receptor activation is followed by a stimulation of adenylate cyclase activity and the elevation of the cAMP level. In the absence of calcium and at high peptide concentrations the cAMP level is lowered via both inhibition of adenylate cyclase and stimulation of cAMP-phosphodiesterase. These different changes in the cAMP level might be correlated with the biphasic pharmacological action of bradykinin in the rat duodenum. The results suggest that one type of bradykinin (B2) receptor is able to initiate several effectuation mechanisms. PMID- 2890348 TI - Glutamate-blood cardioplegia improves ATP preservation in human myocardium. AB - Two groups of patients subjected to radical correction of Fallot's tetrad and defects of interventricular septum were investigated to ascertain whether the addition of glutamic acid to blood cardioplegic perfusate could improve preservation of myocardial ATP during cardiac arrest. In the control group (17 patients) the myocardial protection was performed by repeated infusions of cold blood potassium cardioplegic solution; in the 2nd group (24 patients) cardioplegic perfusate containing glutamic acid (20 mmol/l) was used. Left ventricular biopsies were taken during the first minute after cross-clamping of the aorta and before the release of the aortic clamp to determine ATP, glutamate and lactate. The cross-clamping time averaged 32 min in both groups. In the patients of the control group the losses of ATP correlated with the decrease in glutamate during the clamping period. A maintenance of a higher myocardial glutamate content by glutamate-containing cardioplegic perfusate prevented ATP fall or increased its level in patients of the 2nd group. There was no significant difference in lactate levels between the two groups by the end of the cardiac arrest. We conclude that enrichment of blood cardioplegic solution by glutamic acid, which may act as a substrate for anaerobic energy production, provides more effective myocardial protection during ischemic heart arrest. PMID- 2890349 TI - Induction of zinc-thionein by estradiol and protective effects on inorganic mercury-induced renal toxicity. AB - The castrated or unoperated male rats received an intravenous injection of HgCl2 at a dose of 0.7 mg/kg of body weight (b.w.) after pretreatment with 30% ethanol or estradiol dissolved in 30% ethanol at a dose of 0.5 mg/kg b.w. subcutaneously twice a day for six consecutive days. Renal total protein, gamma-GTP and K excretion in the rats treated with Hg and estradiol were significantly lower than the corresponding values in the rats treated with Hg alone, suggesting that pretreatment with estradiol ameliorates the renal toxicity of Hg in male rats. Pretreatment with estradiol significantly increased Hg and Hg-thionein(Hg-MT) concentrations in the renal cortex of the animals treated with Hg, though in the liver this agent did increase the Hg-MT without elevation of Hg concentration. Treatment with estradiol alone (0.5 mg/kg, s.c., twice a day, for six consecutive days) significantly increased the zinc-thionein (Zn-MT) concentration in the kidney and liver. Simultaneous treatment with 10(-5) M estradiol and Hg in human amniotic-fluid cells caused a significant increase in the uptake of Hg and the synthesis of Hg-MT, suggesting that estradiol may directly stimulate an accumulation of Hg into the cells and the synthesis of Hg-MT. Together, all of the above findings suggest that pretreatment with estradiol may increase the uptake of Hg, which in turn leads to the increase in the Hg-MT concentration. The induction of Zn-MT by pretreatment with estradiol may account for the protective effect of estradiol on Hg-induced renal toxicity. PMID- 2890350 TI - Effects of beta 1- and beta 1 + beta 2-antagonists on training-induced myocardial hypertrophy and enzyme adaptation. AB - The effects of beta 1- and beta 1 + beta 2-antagonists on the myocardial adaptation to exercise training were investigated in male Sprague-Dawley rats randomly divided into trained (treadmill, 1 hr/day, 5 days/week for 10 weeks at 27 m/min, 15% grade) without drug (TC), sedentary without drug (SC), trained treated with atenolol (TA) (10 mg/kg body wt, i.p.), trained treated with propranolol (TP, 30 mg/kg body wt, i.p.), and sedentary propranolol. Doses of both beta-antagonists were titrated to decrease the exercise heart rate by 25% compared to the controls. The heart weight and heart/body weight ratio were significantly greater in TC (1.28 +/- 0.07 g (P less than 0.01); 296 +/- 12 mg/100 g body wt (P less than 0.05) respectively) than in SC (1.09 +/- 0.04 g and 268 +/- 11 mg/100 g body wt), or in TP and TA. Myocardial mitochondrial protein was unchanged by training or beta-blockade. Citrate synthase and beta-hydroxyacyl CoA dehydrogenase activities were not altered. Carnitine palmitoyltransferase activity was increased in SP compared to SC. Training increased hexokinase activity only in TC (5.22 +/- 0.12 vs 4.26 +/- 0.23 mumol/min/g wet wt, P less than 0.01). Lactate dehydrogenase activity increased significantly (P less than 0.01) in both TC (383 +/- 14 mumol/min/g wet wt) and TA (372 +/- 14 mumol/min/g wet wt) compared to SC (276 +/- 14 mumol/min/g wet wt), but not in TP versus SP. These data indicate that (1) beta-adrenergic blockade prevents training-induced cardiac hypertrophy; (2) beta-antagonists have little effect on the myocardial oxidative capacity; and (3) while the training induction of myocardial hexokinase is inhibited by both beta 1- and beta 1 + beta 2-antagonists, myocardium may increase its ability to utilize lactate during exercise with training despite beta 1-blockade. PMID- 2890351 TI - Binding in vitro of pipequaline (45319 RP) onto plasma proteins and blood cells in man. AB - Serum binding of pipequaline, a new anxiolytic drug, was studied in vitro by equilibrium dialysis. The percent binding in serum is high, 96.3%, and remains constant within the range of therapeutic concentrations. Investigations performed on isolated proteins with a wide range of concentrations showed one site with a high affinity constant (Ka = 450,000 M-1) for alpha 1-acid glycoprotein and two sites with a lower affinity constant (Ka = 58,000 M-1) for human serum albumin. Binding to lipoproteins was saturable, with an affinity constant of 22,000 less than or equal to Ka less than or equal to 35,000 M-1. Over the range of therapeutic concentrations, the ratio of pipequaline concentrations in serum and red blood cells remained constant (14.4%) and was shown to be dependent on the free fraction of pipequaline in serum. PMID- 2890352 TI - Alpha-adrenoceptor antagonistic action of amiloride. AB - 1. In isolated perfused rat liver, the effects of alpha-adrenergic stimulation by phenylephrine (2 microM), such as an increase of portal pressure, glucose output, Ca2+ release into the perfusate and the characteristic K+ flux changes across the hepatocyte plasma membrane were almost completely abolished in the presence of amiloride (0.5 mM). 2. When the phenylephrine concentration was raised to about 100 microM, the effects of the alpha-adrenergic agonist on hepatic metabolism, Ca2+ and K+ fluxes, but not on the portal venous pressure, were restored, suggesting a competitive antagonism by amiloride. 3. Amiloride antagonized in a concentration-dependent manner noradrenaline-induced isometric contractions of strips of the rabbit pulmonary artery. The concentration-response curve of noradrenaline was shifted to the right, and the maximal response obtained was also depressed, suggesting a mixed competitive and non-competitive antagonism. The estimated amiloride-adrenoceptor-dissociation constant was 8 microM. 4. The affinity of amiloride to the alpha- and beta-adrenoceptor subtypes was determined by radioligand binding assays using [125I]BE 2254 binding to rat liver plasma membranes (alpha 1-subtype), [3H]yohimbine binding to human platelet membranes (alpha 2-subtype), (-)-[125I]iodocyanopindolol (ICYP) binding to rabbit lung membranes in presence of the beta 2-adrenoceptor antagonist ICI 118,551 (beta 1 subtype) and ICYP binding to rat lung membranes in presence of the beta 1-blocker atenolol (beta 2-subtype). In all systems, amiloride inhibited specific ligand binding concentration-dependently, the Ki values for amiloride were about 25, 52, 148 and 161 microM for alpha 1- alpha 2-, beta 1- and beta 2-adrenoceptor subtypes, respectively. 5. It is concluded that amiloride in concentrations below those required for inhibition of the Na+/H+ exchanger is a potent antagonist of alpha- and beta-adrenoceptors in a variety of experimental systems. Whether the adrenergic antagonism of amiloride is important for antihypertensive therapy, remains to be elucidated. PMID- 2890353 TI - Polarography: a new tool in the elucidation of drug-albumin interactions. PMID- 2890354 TI - The neurotransmitter amino acid transport systems. A fresh outlook on an old problem. PMID- 2890355 TI - The scavenging of oxidants by sulphasalazine and its metabolites. A possible contribution to their anti-inflammatory effects? AB - Sulphasalazine (Salazopyrin) and its metabolites sulphapyridine and 5 aminosalicylate are powerful scavengers of the hydroxyl radical, determined by pulse radiolysis and confirmed by assays based on deoxyribose degradation by hydroxyl radicals. 5-Aminosalicylate can also protect alpha 1-antiprotease against attack by the myeloperoxidase-derived oxidant hypochlorous acid. The ability to scavenge oxidants produced at sites of inflammation may contribute to the anti-inflammatory action of sulphasalazine and its metabolites. PMID- 2890356 TI - Role of the intestinal flora in the acetylation of sulfasalazine metabolites. PMID- 2890357 TI - Preclinical safety evaluation of the benzodiazepine quazepam. AB - 7-Chloro-5-(2-fluorophenyl)-1,3-dihydro-1-(2,2,2-trifluoroethyl)-2H-1,4- benzodiazepine-2-thione (quazepam, Sch 16134, Dormalin) was evaluated for evidence of systemic toxicity, carcinogenicity and reproductive toxicity in several laboratory animal species including the hamster. Mutagenic potential was also assessed in one in vivo and three in vitro assays. In some studies, diazepam was used as a comparative control. Oral LD50 values were greater than 5000 mg/kg in the mouse and rat while i.p. LD50 values were approximately 900 and 2900 mg/kg in the mouse and rat, respectively. Studies in hamsters for 4 weeks at doses up to 500 mg/kg/d and for 51 weeks at doses up to 120 mg/kg/d demonstrated that the liver was the principal target organ in this species with the effects upon the liver related to dose and duration of dosing. Studies in the squirrel monkey for 13 and 52 weeks at doses up to 50 mg/kg/d demonstrated a transient ataxia, hypoactivity and somnolence during the initial two weeks of dosing. No unusual necropsy or microscopic observations were noted in the 13-week study. Male reproductive organs of quazepam-dosed monkeys were reduced in weight after 52 weeks. Moderate to marked impairment of spermatogenesis and higher liver weights with moderate to marked fatty change in both sexes were observed in groups given diazepam. Abrupt withdrawal of quazepam or diazepam after 52 weeks of dosing was associated at all dose levels with excitability, hyperactivity and convulsions. Two quazepam- and all diazepam-dosed monkeys died.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890358 TI - Effect of cimetidine on the pharmacokinetics of the new beta-blocker betaxolol. AB - The effect of cimetidine on the new beta-blocker betaxolol (Kerlone) was investigated in 7 healthy volunteers. Propranolol was used as a reference beta blocking drug. In the control study, a single oral dose of propranolol (80 mg) was given (D0) followed by 5 daily doses of cimetidine (1 g) (D1-D6) and a second oral dose of propranolol (D7). The study was repeated with 20 mg of betaxolol replacing the propranolol dose. The oral clearance of propranolol was significantly decreased (21%). No significant effect of cimetidine on the kinetics of betaxolol was observed. PMID- 2890359 TI - Apolipoprotein B gene variants are involved in the determination of serum cholesterol levels: a study in normo- and hyperlipidaemic individuals. AB - We have investigated the frequencies of 3 restriction fragment length polymorphisms (RFLPs) of the apolipoprotein B (apo B) gene in normo- and hyperlipidaemic individuals. In individuals with type III hyperlipidaemia, the allele frequency for the RFLP detected with XbaI was significantly different from the allele frequency in normolipidaemic individuals and in those with other types of hyperlipidaemia. No significant difference in allele frequency was found among these groups for the RFLPs detected with MspI or EcoRI. Within a sample of 62 normolipidaemic individuals, homozygotes for the X2 allele (cutting site) of the XbaI RFLP had a significantly higher serum cholesterol level than homozygotes for the XI allele, with individuals of the genotype X1X2 having an intermediate value (X2X2 mean 5.71 mmol/l, X1X1 mean 4.81 mmol/l, X1X2 mean 5.30 mmol/l). There were also significant differences in serum triglyceride levels in individuals with different XbaI genotypes. In these normolipidaemic individuals there was no correlation between the EcoRI and MspI RFLP genotypes and levels of any serum lipid variable. Information from the XbaI and EcoRI RFLPs was used in conjunction to define apo B haplotypes. These haplotypes are a more precise measure of the genotypic variation, and they explain a greater fraction of the serum cholesterol and triglyceride levels than the single-site polymorphisms considered separately. This study suggests that variations in the gene for apo B are associated with the determination of serum cholesterol and triglyceride levels both in patients with type III hyperlipidaemia and in the normal population. PMID- 2890360 TI - [Study and management of cryptorchism: gonadotropin and orchiopexy]. PMID- 2890361 TI - Thy-1 solubilization from mouse T cells by phosphatidylinositol-specific phospholipase C: biochemical and antigenic characterization. AB - Membrane anchorage of mouse and rat Thy-1 antigens results from the post translational attachment of a non-proteic tail terminated by a phosphatidylinositol group. In order to determine the biochemical and antigenic properties of the material released by phosphatidylinositol-specific phospholipase C (PI-PLC), we studied, by one-(1-D) and two-dimensional (2-D) gel electrophoresis and by immunoprecipitation, the supernatant of surface-labelled mouse T cells treated with purified Staphylococcus aureus PI-PLC. The major protein released by this enzymatic treatment showed an apparent molecular weight (MW) and an isoelectric focusing (IEF) pattern identical to those of detergent solubilized, immunoprecipitated Thy-1. In addition, a sandwich radioimmunoassay (RIA) utilizing two Thy-1-specific monoclonal antibodies (mAb) was used to quantitate the amounts of PI-PLC-released and spontaneously shed Thy-1. Considerable differences in susceptibility to enzymatic cleavage and in spontaneous shedding were observed for a variety of mouse T-cell populations, including thymocytes and hybridoma, helper and cytotoxic cloned T cells, even though time-course experiments demonstrated that excess enzyme was used. It might be useful to consider these differences in the cell biology of Thy-1 and the occurrence of other PI-linked proteins of the lymphocyte surface in terms of their implications in the transduction of activation signals. PMID- 2890362 TI - Residual myocardial jeopardy in patients with Q-wave and non-Q-wave infarctions. AB - The correlation between the presence of areas of jeopardized myocardium and the electrocardiographic patterns of anterior and inferior Q-wave and non-Q-wave infarctions was studied in 486 patients who had had stable symptoms for at least six months after a single myocardial infarction. Myocardial jeopardy was identified on a ventriculogram in the right anterior oblique position if normal or hypokinetic wall motion was seen in all segments distal to a lesion that caused stenosis of greater than 50% and less than 100% in the proximal or mid left anterior descending coronary artery (anterior jeopardy), or in the proximal or mid right coronary artery or proximal circumflex coronary artery in a left dominant circulation (inferior jeopardy). Patients with non-Q-wave anterior infarctions had a significant increase in the frequency of jeopardized myocardium when compared with patients with Q-wave inferior or anterior infarctions. The group with non-Q-wave anterior infarction also had a significantly lower percentage of myocardial segments with absent wall motion in the area of infarction than all other groups. This combination of coronary narrowing with retained wall motion may contribute to the increased frequency of reinfarction seen in some studies of non-Q-wave infarction. PMID- 2890363 TI - Pre-treatment with beta blockers and the frequency of hypokalaemia in patients with acute chest pain. AB - Plasma potassium concentration was measured at admission in 1234 patients who presented with acute chest pain. One hundred and ninety five patients were on beta blockers before admission. The potassium concentrations of patients admitted early (within four hours of onset of symptoms) were compared with those admitted later (4-18 hours after onset of symptoms). There was a transient fall in plasma potassium concentrations in patients not pre-treated with beta blockers. This was not seen in patients who had been on beta blockers before admission. Non selective beta blockers were more effective than cardioselective agents in maintaining concentrations of plasma potassium. These findings suggest a mechanism for the beneficial effects of beta blockers on morbidity and mortality in acute myocardial infarction. PMID- 2890364 TI - An evaluation of priming with vecuronium. AB - Priming with vecuronium was evaluated in three groups of patients. Group 1 (n = 10) received tubocurarine 0.05 mg kg-1, group 2 (n = 19) received physiological saline and group 3 (n = 21) received vecuronium 0.012 mg kg-1. After 4 min maximum inspiratory pressure was measured. Anaesthesia was induced with thiopentone 6-8 mg kg-1 and controlled ventilation with nitrous oxide and oxygen via a face mask instituted. The ulnar nerve was stimulated at the wrist. At 5 min group 1 patients received suxamethonium 1.5 mg kg-1, group 2 received vecuronium 0.072 mg kg-1, and group 3 received vecuronium 0.060 mg kg-1. Intubation was accomplished at 6.5 min in all patients in group 1, 89% in group 2 and 90% in group 3. Patients in group 1 had no twitch response to stimulation at the time of intubation. Mean T4:T1 ratios at 6.5 min were 0.82 in group 2 and 0.61 in group 3 (P less than 0.05). Intubating conditions were excellent in all group 1 patients, and in 53% and 67% of groups 2 and 3, respectively. Two patients in group 3 did not tolerate the priming dose and many had subjective complaints. Four group 3 patients could not sustain head lift and five showed decreased inspiratory pressure. Priming did not improve intubating conditions when compared with a single bolus technique and was not well tolerated. PMID- 2890365 TI - Vecuronium or suxamethonium for rapid sequence intubation: which is better? AB - The effects of suxamethonium, and of vecuronium given after three subparalyzing (priming) doses, on the time of onset of neuromuscular blockade and on the resultant intubating conditions were compared. This study involved five groups of 10 patients (ASA class I or II) who were premedicated with flunitrazepam 0.015 mg kg-1 i.m. Anaesthesia was induced with thiopentone 6 mg kg-1 and fentanyl 0.003 mg kg-1. In groups 2, 3 and 4 the patients were given a priming dose of vecuronium 0.01, 0.015 and 0.02 mg kg-1, respectively. Three minutes later the intubating dose of vecuronium was given: 0.1 mg kg-1 (group 1), 0.09 mg kg-1 (group 2), 0.085 mg kg-1 (group 3), 0.08 mg kg-1 (group 4). When the electromyographic response was 95% of control, the trachea was intubated. In groups 2, 3 and 4, the onset time was significantly decreased compared with group 1. Increasing the priming dose from 0.01 mg kg-1 did not offer any advantage. The duration of blockade (time from the intubating dose to 15% recovery) was not significantly increased with any priming dose. In group 5, the trachea was intubated after suxamethonium 1.5 mg kg-1. Mean onset time, which was significantly shorter than in the other groups, was half that of the groups that received a priming dose. Intubation conditions were better in group 5 than in the other groups (P less than 0.01). PMID- 2890366 TI - Influence of "priming" on the potency of non-depolarizing neuromuscular blocking agents. AB - Dose-response curves have been constructed to determine the ED50 and ED95 (doses required to produce a 50% and a 95% block, respectively) following administration of a small "priming" dose of atracurium 50 micrograms kg-1, vecuronium 10 micrograms kg-1 or pancuronium 10 micrograms kg-1. The myoneural blockers were administered subsequently as a single bolus. The results were compared with previously published work on these drugs, in which no priming dose had been administered. The respective ED50 and ED95 values in the primed and control groups were 122 and 126 micrograms kg-1 and 208 and 226 micrograms kg-1, respectively, for atracurium; 26 and 23 micrograms kg-1 and 42 and 39 micrograms kg-1, respectively, for vecuronium; and 31 and 30 micrograms kg-1 and 56 and 60 micrograms kg-1, respectively, for pancuronium. The values showed no significant differences between the respective primed and control groups. Contrary to previous suggestions, our results show no enhancement of blockade when these drugs were administered in divided doses. PMID- 2890367 TI - Serum activity of gamma-glutamyltranspeptidase (GGT) in relation to estimated alcohol consumption and questionnaires in alcohol dependence syndrome. PMID- 2890368 TI - Serum gamma-glutamyltransferase: an epidemiological indicator of alcohol consumption? PMID- 2890369 TI - Treatment of severe psoriasis with etretin (RO 10-1670). AB - Eighty patients with severe psoriasis were treated in a double-blind fashion with either an initial dose of 10 mg, 25 mg or 50 mg of etretin daily or with placebo. Follow-up examinations were carried out monthly and the efficacy of treatment was evaluated by using the PASI score. Adverse effects of the treatment were recorded monthly; liver enzymes, cholesterol and triglycerides were measured. After 2 months of treatment the maintenance dose was reduced in some of the patients either because of complete remission or adverse effects. After 2 months treatment, groups receiving 25 mg/day and 50 mg/day showed significantly lower PASI scores than the placebo group. The 10 mg/day group showed a response intermediate between the 25 mg and 50 mg groups and the placebo group. Thus, the optimal initial dose seems to be approximately 25 mg/day and the maintenance dose somewhat lower. Six months after the start of treatment there were no significant differences between the four groups; the last follow-up examination took place during the summer and some of the patients probably experienced spontaneous improvement. Although clinical adverse effects were frequent in all groups, severe side effects, namely hair loss and paronychia, occurred frequently only among patients treated with an initial dose of 50 mg of etretin daily. The effect of treatment on liver enzymes, cholesterol and triglycerides was minimal. PMID- 2890370 TI - Beta-thalassaemia in Campania: DNA polymorphism analysis in beta A and beta thal chromosomes and its usefulness in prenatal diagnosis. AB - In order to evaluate the feasibility of first trimester prenatal diagnosis of beta-thalassaemia by restriction fragment length polymorphism (RFLP) in Campania, one of the most affected regions in Southern Italy, DNA polymorphism analysis was performed on 40 unrelated patients, affected with homozygous beta-thalassaemia, and on their parents. Frequency of the presence of the Hinc II epsilon, Hind III G gamma and A gamma, Hinc II psi beta and 3' psi beta, Ava II psi beta, Ava II beta and Bam HI 3' beta sites have been determined in the beta A and beta thal chromosome samples. In 31 families (over 75%), RFLPs enabled tracing the beta thalassaemia mutations in both father and mother (100% diagnosis). In the remaining nine families, RFLPs enabled tracing only one of the two mutations (50% diagnosis) because the other parent was found to be homozygous in all the analysed polymorphic sites. Restriction haplotypes, assembled on the basis of linkage analysis, were most heterogeneous, hence a wide heterogeneity of mutations is expected. PMID- 2890371 TI - Use of circulating stem cells to accelerate myeloid recovery after autologous bone marrow transplantation. PMID- 2890372 TI - Comparative studies on the hypercholesterolaemia induced by excess dietary tyrosine or polychlorinated biphenyls in rats. AB - 1. The effects of dietary polychlorinated biphenyls (PCB) and excess tyrosine on serum and liver lipids, urinary ascorbic acid and catecholamines were compared in male Wistar rats. 2. Serum levels of cholesterol, urinary ascorbic acid, norepinephrine, epinephrine, dopamine and histamine were significantly increased in rats given either PCB or excess tyrosine. 3. The hypercholesterolaemia induced by PCB or excess tyrosine was blocked by the adrenergic alpha-blocker, phenoxybenzamine. 4. The present results suggest causal interrelations between the hypercholesterolaemia induced by dietary PCB or excess tyrosine and the secretion of catecholamines. PMID- 2890373 TI - Characterization of the M1(Ala213) type of alpha 1-antitrypsin, a newly recognized, common "normal" alpha 1-antitrypsin haplotype. AB - alpha 1-Antitrypsin (alpha 1AT) is a highly pleomorphic 52-kDa serum glycoprotein that functions as the major inhibitor of neutrophil elastase. Of these, the most common normal alpha 1AT haplotypes identified by isoelectric focusing (IEF) of serum are those of the M family, including M1, M2, and M3. In the course of studying the alpha 1AT type Z gene, we identified a restriction endonuclease BstEII polymorphism in the M1 gene that predicted the existence of a previously unidentified, but relatively common, haplotype of M, referred to as M1(Ala213) [Nukiwa, T., Satoh, K., Brantly, M. L., Ogushi, F., Fells, G. A., Courtney, M., & Crystal, R. G. (1986) J. Biol. Chem. 261, 15989-15994]. In this study we have cloned both alpha 1AT genes from an individual heterozygous for the M1(Ala213) and M1(Val213) haplotypes. Sequencing of the coding exons of both demonstrated that they are identical except for the Ala-Val difference at residue 213. The codominant transmission of the M1(Ala213) gene was demonstrated in a family study. Evaluation of 39 genomic samples of Caucasians with the IEF haplotype M1 demonstrated haplotype frequencies of 68% for M1(Val213) and 32% for M1(Ala213). alpha 1AT serum levels of individuals inheriting the M1(Ala213) gene in a homozygous fashion were in the same range as those for homozygous M1(Val213) as was the rate of association of the M1(Ala213) protein with neutrophil elastase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890374 TI - Site-directed mutagenesis of glutamate-190 in the hinge region of yeast 3 phosphoglycerate kinase: implications for the mechanism of domain movement. AB - In order to evaluate a possible contribution of glutamate-190, situated in the hinge region of yeast 3-phosphoglycerate kinase (PGK), to the mechanism of the substrate- and sulfate-induced domain movement, we have constructed two point mutants, Gln-190 and Asp-190, using oligonucleotide-directed in vitro mutagenesis. The Michaelis constants of the mutants for ATP and 3 phosphoglycerate were not significantly altered, whereas the catalytic activities were decreased, both in the absence and in the presence of sulfate ions. In the absence of sulfate, the Gln-190 and Asp-190 mutants exhibited 26% and 36% of the activity of the native enzyme. In the presence of 30 mM Na2SO4, a concentration at which native PGK exhibits maximum activation, the relative activities of the Gln-190 and Asp-190 mutants were 6% and 9%, respectively. In contrast to the native enzyme, which undergoes activation at low sulfate concentrations and inhibition at high concentrations, both mutants showed a complete loss of the salt activation effect. These results suggest that Glu-190 is not directly involved in the binding of substrates but might be important for conformational flexibility. We have also demonstrated that, similarly to native PGK, both mutants are completely inactivated by the incorporation of 1 mol of glycine ethyl ester/mol of enzyme. Appreciable protection against inactivation is observed in the presence of both substrates, MgATP and 3-phosphoglycerate. Only limited protection is observed in the presence of the individual substrates, suggesting that the modification does not occur at the substrate binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890375 TI - F0 portion of Escherichia coli ATP synthase: orientation of subunit c in the membrane. AB - Incubation of right-side-out oriented membrane vesicles of Escherichia coli with tetranitromethane resulted in the nitration of tyrosine residues (Tyr-10 and Tyr 73) of subunit c from the ATP synthase. Cleavage of the protein with cyanogen bromide and separation of the resulting fragments, especially of the tyrosine containing peptides, clearly demonstrated that the distribution of the nitro groups is similar at any time and at any pH value chosen for the analysis. Furthermore, the percentage of 3-nitrotyrosine present in the two peptide fragments was in good agreement with that obtained for the intact polypeptide chain. While the modification of the tyrosine residues in subunit c with the lipophilic tetranitromethane is independent of the orientation of the membrane vesicles, the subsequent partial conversion of the 3-nitrotyrosine to the amino form only occurred when membrane vesicles with right-side-out orientation were treated with the ionic, water-soluble sodium dithionite, which at certain concentrations cannot penetrate biological membranes. Cleavage of subunit c isolated from nitrated and subsequently reduced membrane vesicles and separation of the resulting fragments by high-pressure liquid chromatography showed that the 3-nitrotyrosine in the Tyr-73-containing peptides has been completely reduced, while the nitro group in peptides containing Tyr-10 remained nearly unaffected. PMID- 2890376 TI - Catalytic hydrolysis and synthesis of adenosine 5'-triphosphate by stereoisomers of covalently labeled F1-adenosinetriphosphatase and reconstituted submitochondrial particles. AB - Bovine heart F1-adenosinetriphosphatase (F1) was labeled specifically and precisely with 7-chloro-4-nitro-2,1,3-[14C]benzoxadiazole ([14C]NBD-Cl). The stereospecifically labeled F1 (O-beta'-[14C]-NBD-F1) was partially reactivated by LiCl treatment, which could cause rearrangement of the beta subunits to form O beta', beta''-[14C]NBD-F1. Both labeled enzymes were used to combine with F1 deficient submitochondrial particles (ASU) to form the reconstituted particles O beta'-NBD-F1-ASU and O-beta', beta''-NBD-F1-ASU, respectively. A comparison of the observed steady-state rates of catalytic ATP hydrolysis and oxidative phosphorylation by these specifically labeled submitochondrial particles (SMP) with those of the unlabeled control samples suggests that oxidative phosphorylation involves more active sites of F1 than catalytic ATP hydrolysis. A comparison of the observed ATPase activity of uncoupled labeled SMP and the activity for ATP-driven reverse electron transport in coupled labeled SMP with the corresponding values of the unlabeled control samples shows that the observed fractional inhibition ATP hydrolysis is the same for both the coupled SMP and uncoupled SMP and is determined only by the state of stereospecific labeling of F1. The effect of preincubation under simulated oxidative phosphorylation conditions on the ATPase activity of the unperturbed, specifically NBD-labeled submitochondrial particles was also examined. The data show that respiration generated proton flux does not cause the beta subunits in bovine heart proton ATPase to continue switching places with each other during oxidative phosphorylation. Samples of NBD-F1 with specific labels on its nonhydrolytic beta'' subunits but none on its hydrolytic beta' subunit were prepared by a three cycle process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890377 TI - Ligand-induced conformational changes in the Escherichia coli F1 adenosine triphosphatase probed by trypsin digestion. AB - Digestion of the F1-ATPase of Escherichia coli with trypsin stimulated ATP hydrolytic activity and removed the delta and epsilon subunits of the enzyme. A species represented by the formula alpha 1(3) beta 1(3) gamma 1, where alpha 1, beta 1 and gamma 1 are forms of the native alpha, beta and gamma subunits which have been attacked by trypsin, was formed by trypsin digestion in the presence of ATP. In the presence of ATP and MgCl2, conversion of gamma to gamma 1 was retarded and the enzyme retained the epsilon subunit. These results imply that binding of ATP to the beta subunits alters the conformation of ECF1 to increase the accessibility of the gamma subunit to trypsin. The likely trypsin cleavage sites in the alpha, beta and gamma subunits are discussed. ECF1 from the alpha subunit-defective mutant uncA401, or after treatment with N,N' dicyclohexylcarbodiimide or 4-chloro-7-nitrobenzofurazan, was present in a conformation in which the gamma subunit was readily accessible to trypsin and could not be protected by the presence of ATP and MgCl2. In a similar manner to native E. coli F1-ATPase, the hydrolytic activity of the trypsin-digested enzyme was stimulated by the detergent lauryldimethylamine N-oxide. Since the digested enzyme lacked the epsilon subunit, a putative inhibitor of hydrolytic activity, a mechanism for the stimulation which involves loss or movement of this subunit is untenable. PMID- 2890378 TI - Dissociation-reconstitution experiments support the presence of two catalytic beta-subunits in mitochondrial F1. AB - Mitochondrial F1, inactivated to various extents with 4-chloro-7-nitrobenzo-2-oxa 1,3-diazole (NBD-Cl), was dissociated with LiCl and reconstituted after removal of the salt. This procedure resulted in a reactivation that corresponded with a reactivation theoretically expected on the basis of the assumption that the reassociation of beta-subunits into native F1 molecules is random and that two out of the three beta-subunits are directly involved in catalysis. Repeated inactivation of such reactivated F1, followed by the same dissociation association procedure, resulted in similar data. After inactivation of F1 by covalent binding of 2-N-AT(D)P to one catalytic site, no reactivation upon dissociation-reassociation was obtained due to the fact that such modified F1 did not dissociate under the experimental conditions used. PMID- 2890379 TI - Defective distal regulatory element at the 5' upstream of rat prolactin gene of steroid-nonresponsive GH-subclone. AB - The prolactin-nonproducing (PRL-) GH cell strains (rat pituitary tumor cells in culture). GH12C1 and F1BGH12C1, do not respond to steroid hormones estradiol or hydrocortisone (HC). However, the stimulatory effect of estradiol and the inhibitory effect of hydrocortisone on prolactin synthesis can be demonstrated in the prolactin-producing GH cell strain, GH4C1. In this investigation we have examined the 5' end flanking region of rat prolactin (rat PRL) gene of steroid responsive, GH4C1 cells to identify the positive and negative regulatory elements and to verify the status of these elements in steroid-nonresponsive F1BGH12C1 cells. Results presented in this report demonstrate that the basel level expression of the co-transferred Neo gene (neomycin phosphoribosyl transferase) is modulated by the distal upstream regulatory elements of rat PRL gene in response to steroid hormones. The expression of adjacent Neo gene is inhibited by dexamethasone and is stimulated by estradiol in transfectants carrying distal regulatory elements (SRE) of steroid-responsive cells. These responses are not observed in transfectants with the rat PRL upstream sequences derived from steroid-nonresponsive cells. The basal level expression of the host cell alpha-2 tubulin gene is not affected by dexamethasone. We report here the identification of the distal steroid regulatory element (SRE) located between 3.8 and 7.8 kb upstream of the transcription initiation site of rat PRL gene. Both the positive and the negative effects of steroid hormones can be identified within this upstream sequence. This distal SRE appears to be nonfunctional in steroid nonresponsive cells. Though the proximal SRE is functional, the defect in the distal SRE makes the GH substrain nonresponsive to steroid hormones. These results suggest that both the proximal and the distal SREs are essential for the mediation of action of steroid hormones in GH cells. PMID- 2890380 TI - Interaction of phosphonates related to glutathione with the rat kidney gamma glutamylcysteine synthetase. AB - Various phosphonic and sulfonic glutamate analogues as well as phosphonopeptides related to glutathione were studied for their interaction with rat kidney gamma glutamylcysteine synthetase activity. We found, in all cases, that the presence of a phosphonic group increases the affinity for the enzyme. Among the tripeptides tested, the phosphonic analogue of ophthalmic acid (gamma Glu-Abu-Gly P) is the most potent inhibitor. The glutamate and cysteine sites of the enzyme seem to be involved in the binding of this compound, since either substrate protects against inhibition. The types of inhibition with respect to the different substrates show dissimilar behaviors of the tripeptides, in spite of their structural analogy. Investigations relative to the role of the divalent ion Mg2+ provided evidence that the actual inhibitors are Mg2+-tripeptide complexes for the phosphonic compounds, whereas chelation with a metal ion is not required for inhibition by glutathione. PMID- 2890381 TI - [Molecular organization of glutamate-sensitive chemo-stimulated nerve cell membranes. Interaction of monoclonal antibodies with glutamate-binding membrane proteins in the rat brain, human neuroblastoma and molluscan neurons]. AB - Hybrid cells obtained by fusion of myeloma PX63-Ag8-653 with immune splenocytes of BALB/c mice were found to produce monoclonal antibodies with a high degree of specificity to rat and human brain. The kinetics of specific IgG binding to purified fractions of glutamate-binding membrane proteins from rat and human brain were analyzed in Scatchard plots. The presence of a single type of binding sites with Kd = 100 nM was demonstrated. The monoclonal antibodies were shown to inhibit the specific binding of tritium-labeled L-glutamate to different brain synaptic membranes. Addition of monoclonal antibodies to the incubation medium induced a modulating effect of physiological responses to L-glutamate in Planorbarius corneus neurons. The possible use of specific antibodies to glutamate-binding proteins as immunochemical markers for the study of glutamate receptor topography on membrane surface was demonstrated with the aid of neuroblastoma cells N18 Tg2a and rat brain tissue slices. An analysis of glutamate receptor binding sites with the use of monoclonal antibodies revealed that these antibodies specifically recognize the active center in the receptor molecules which have identical antigen determinant sites in different biological systems. PMID- 2890382 TI - Beta-adrenergic blockers decrease levels of luteinizing hormone in plasma of orchidectomized rats. AB - The beta-adrenergic antagonists, propranolol and bornaprolol (FM-24), at greater than 2 mg/kg (as [-] form) significantly depressed plasma levels of luteinizing hormone (LH) in orchidectomized rats. This occurred in the absence of consistently significant changes in interpulse intervals or amplitudes of pulsatile LH release. Nadirs of plasma LH decreased significantly even at low blocker doses, with a clear dose dependence for both drugs. The highly significant decrease of plasma LH induced by blocker dosages causing greater than 93% inhibition of beta-adrenergic binding in the anterior pituitary gland was shown to occur without significant changes in binding of specific ligands at pituitary dopamine receptors and hypothalamic alpha 1-adrenergic receptors. The above evidence indicates that beta-blockers may lower LH release in vivo at the level of pituitary beta-adrenergic receptors. PMID- 2890384 TI - [Antibodies to morphine and neuromediators in the blood serum of chronic alcoholics]. AB - The data on the presence of antibodies to morphine and neurotransmitters (dopamine, norepinephrine, serotonin) in the blood serum of chronic alcoholics are presented. The antibodies were detected by the modification of complement fixation test. 82% of chronic alcoholics showed significantly elevated levels (P less than 0.01) of antibodies to morphine (5.34 +/- 0.65% of complement fixed) when compared to the control group (2.41 +/- 0.52% of complement fixed), which was an indirect evidence of the presence of endogenous morphine-like compounds in men and their role in the pathogenesis of the disease. A general group of alcoholics could be divided into subgroups with significantly elevated and decreased levels of antibodies to the appropriate neurotransmitter, as compared to the control group, which significantly differed from each other. Similar results were obtained in chronically alcoholized rats. PMID- 2890383 TI - [Ratio of brain synaptosome Na, K-ATPase to dopamine receptors]. AB - Activating (0.3-3 microM) or inhibitory (0.03-0.3 mM) effects of dopamine (DA) in the absence of Ca2+, and its inhibitory effect in the presence of Ca2+ on Na,K ATPase activity of synaptosomes from the caudate nucleus of the rat brain were confirmed. Na,K-ATPase was shown to be inhibited by 6 neuroleptics, with the degree of inhibition stronger in the presence of Ca2+. It was found that: 1) the biphasic or monophasic nature of DA action on Na,K-ATPase activity was preserved in the presence of neuroleptics, 2) DA enhances the inhibitory effects of neuroleptics on the enzyme, 3) the inhibitory effects of DA on Na,K-ATPase are enhanced by Ca2+ ions. The mechanisms of the modifying action of DA on synaptosomal Na,K-ATPase are discussed. PMID- 2890385 TI - [Effect of fentolamin on the resistance of the coronary vessels and on the frequency of the heart rate]. AB - The effects of phentolamine on coronary resistance and heart rate, as well as the influence of beta 1-adrenoceptor blockade on phentolamine effects were studied on the isolated cat hearts. Phentolamine reduced coronary resistance in 100% of cases (-25.9 +/- 4.4%; p less than 0.001) and increased heart rate only in 31.6% of cases (+9.1 +/- 1.4%); on average the alterations of heart rate were nonsignificant (p less than 0.1). After beta 1-blockade with Cordanum the rate of coronary dilation reduced (p less than 0.001), the changes in coronary resistance being nonsignificant (p greater than 0.1). Basal coronary resistance and tone during phentolamine infusion without or after beta 1-blockade were identical (p greater than 0.1). Thus, the reduction of coronary resistance during phentolamine infusion was due to beta 1-adrenomimetic activity of the drug. PMID- 2890386 TI - [Peptidoglycan isolated from Lactobacillus bulgaricus: its effect, mediated by the complement system, on pre-T-cell maturation]. AB - Peptidoglycan from Lactobacillus bulgaricus converts mouse pre-T-cells into theta positive cells and activates the complement. It has been observed that the effect depends on serum peptidoglycan concentration and the time of the interaction of the activated complement with mouse pre-T-cells. The action of peptidoglycan was replaced by C3a complement component. PMID- 2890387 TI - [Criteria of the sensitivity of Zajdela and Morris hepatoma cells to glucocorticoids]. AB - Glucocorticoids induce tyrosine aminotransferase synthesis in 7777 Morris hepatoma but fail to do so in Zajdela hepatoma. This internal property indicates the resistance to the hormone. However, both hepatoma cell lines do respond to the triamcinolone acetonide in a similar way, as judged by some other criteria, e. g. interaction with the immobilized hormone on the inert carrier, adhesion to glass and kinetic parameters of alkaline phosphodiesterase I activity. Moreover, both cell types respond to glucocorticoids by modification of synthesis of some proteins, as revealed previously by two-dimensional electrophoresis. The results show that in case of tumour cells which retain their specific receptor apparatus but do not respond to glucocorticoids by usual criteria, the conclusion whether tumour cells are hormone-sensitive or not has to be drawn from the analysis of their multiple response judging by several assays. PMID- 2890388 TI - Long-term monoclonal reconstitution of erythropoiesis in genetically anemic W/Wv mice by injection of 5-fluorouracil-treated bone marrow cells of Pgk-1b/Pgk-1a mice. AB - The spleen colony-forming assay does not represent the number of hematopoietic stem cells with extensive self-maintaining capacity because five to 50 spleen colony-forming units (CFU-S) are necessary to rescue a genetically anemic (WB X C57BL/6)F1-W/Wv(WBB6F1-W/Wv) mouse. We investigated which is more important for the reconstitution of erythropoiesis, the transplantation of multiple CFU-S or that of a single stem cell with extensive self-maintaining potential. The electrophoretic pattern of hemoglobin was used as a marker of reconstitution and that of phosphoglycerate kinase (PGK), an X chromosome-linked enzyme, as a tool for estimating the number of stem cells. For this purpose, we developed the C57BL/6 congeneic strain with the Pgk-1a gene. Bone marrow cells were harvested after injection of 5-fluorouracil from C57BL/6-Pgk-1b/Pgk-1a female mice in which each stem cell had either A-type PGK or B-type PGK due to the random inactivation of one or two X chromosomes. When a relatively small number of bone marrow cells (ie, 10(3) or 3 X 10(3] were injected into 200-rad-irradiated WBB6F1-W/Wv mice, the hemoglobin pattern changed from the recipient type (Hbbd/Hbbs) to the donor type (Hbbs/Hbbs) in seven of 150 mice for at least 8 weeks. Erythrocytes of all these WBB6F1-W/Wv mice showed either A-type PGK alone or B-type PGK alone during the time of reconstitution, which suggests that a single stem cell with extensive self-maintaining potential may sustain the whole erythropoiesis of a mouse for at least 8 weeks. PMID- 2890389 TI - Seminoma after "orchidectomy": a salutary tale. PMID- 2890390 TI - Effectiveness of benzodiazepines. PMID- 2890391 TI - Neuropharmacological and neurochemical properties of N-(2-cyanoethyl)-2 phenylethylamine, a prodrug of 2-phenylethylamine. AB - 1 N-(2-cyanoethyl)-2-phenylethylamine (CEPEA) was examined as a possible prodrug of 2-phenylethylamine (PEA). 2 Pharmacokinetics of PEA and CEPEA were investigated in rat brain, blood and liver by gas chromatography with electron capture detection (GC-ECD). Interactions of PEA and CEPEA with putative neurotransmitter amines were investigated by use of high performance liquid chromatography with electrochemical detection (h.p.l.c.-e.c.). 3 Administration of PEA caused transient increases in PEA concentrations which decreased rapidly in brain and blood and at a slower rate in liver. Administration of CEPEA caused sustained elevations of PEA concentrations and elimination of PEA was markedly decreased in these tissues relative to the situation after administration of PEA itself. 4 Administration of CEPEA caused more prolonged decreases in brain noradrenaline, dopamine and 5-hydroxytryptamine concentrations than those observed after PEA administration, although values increased to control levels eventually. PMID- 2890392 TI - Inhibition of Uptake1 by dopexamine hydrochloride in vitro. AB - 1 Dopexamine hydrochloride, a compound under evaluation for the acute treatment of heart failure, was examined in vitro for its ability to prevent neuronal uptake of noradrenaline. 2 Despite possessing only weak beta 1-adrenoceptor agonist activity in paced guinea-pig left atria, dopexamine hydrochloride was only 23 times less potent than isoprenaline in augmenting responses of field stimulated atrial preparations. 3 This potent effect was not observed in field stimulated atria depleted of noradrenaline by reserpine and in the presence of cocaine was greatly reduced (1 microM) or abolished (50 microM). 4 Dopexamine hydrochloride (3 microM) potentiated the inotropic effect of exogenous noradrenaline in paced atria, thereby resembling cocaine (10 microM) and dopamine (30 microM), both of which are known inhibitors of Uptake. 5 The sodium-dependent uptake of [3H]-noradrenaline into rabbit brain synaptosomes was prevented by dopexamine hydrochloride (IC50 26 nM) and cocaine (IC50 108 nM), as well as by two other catecholamines used in the treatment of heart failure, dopamine (IC50 270 nM) and dobutamine (IC50 380 nM). 6 The cardiac stimulant effect of dopexamine hydrochloride reported in dogs and in patients with heart failure, may therefore be due in part to potentiation of endogenous catecholamines. PMID- 2890393 TI - Evidence that 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT) is a selective alpha 2-adrenoceptor antagonist on guinea-pig submucous neurones. AB - 1 Intracellular recordings were made from neurones of the submucous plexus and from submucosal arteriolar smooth muscle of guinea-pig ileum for the purpose of examining the the actions of 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT). 2 8-OH-DPAT (10 nM-20 microM) had no direct presynaptic or postsynaptic actions on submucous plexus neurones. 3 Membrane hyperpolarizations induced in neurones by noradrenaline or UK 14304 were competitively antagonized by 8-OH-DPAT. For dose ratios up to 40, Schild plots were linear with slopes not significantly different from unity; pA2 values for the 8-OH-DPAT antagonism of postsynaptic alpha 2 adrenoceptors were 6.9-7.2. 4 The inhibitory synaptic potential, which is due to activation of alpha 2-adrenoceptors located on submucous plexus neurones, was selectively inhibited by 8-OH-DPAT; the IC50 value for inhibition of the inhibitory synaptic potential was 250 nM. 5 Neuronal hyperpolarizations mediated through activation of delta-opioid receptors or somatostatin receptors were unaffected by 8-OH-DPAT (0.1-1 microM). 6 The ability of noradrenaline and UK 14304 to inhibit the release of acetylcholine at synapses in the submucous plexus, and to inhibit the release of the transmitter which mediates the excitatory junction potential in the submucosal arteriolar smooth muscle, was also blocked by 8-OH-DPAT. 7 These results suggest that some of the actions of 8 OH-DPAT previously ascribed to agonism at 5-hydroxytryptamine (5-HT) receptors may actually result from blockade of the actions of endogenously released noradrenaline acting on alpha 2-adrenoceptors. PMID- 2890395 TI - Atypical germ cells in prepubertal cryptorchid testes. AB - Four cases of prepubertal cryptorchid testes with atypical germ cells were studied. These cells were characteristically large, showing a wide, pale cytoplasm and a large nucleus with both fine and coarse granular chromatin. Ferritin was shown to be absent. It is possible that these cells are dysplastic in nature and that they could form the basis of a premalignant intratubular lesion. Thus periodic follow-up of these patients is recommended. PMID- 2890394 TI - Positive inotropic effects of histamine in anaesthetized dogs. AB - 1 The cardiovascular effects of histamine were examined in dogs anaesthetized with pentobarbitone 2 The effect of histamine on heart rate, blood pressure, left ventricular pressure, dP/dtmax and dP/dt: IIT (integrated isometric tension) was compared in the presence and absence of autonomic reflexes and blood pressure control. 3 In innervated animals with no attempt to control blood pressure, histamine produced dose-dependent decreases in blood pressure and heart rate and either positive or negative inotropic actions. 4 When autonomic reflexes were abolished, this variability in inotropic response was reduced and histamine produced a slight positive inotropic response. There was a decrease in blood pressure and a positive chronotropic response to histamine. 5 When blood pressure was controlled and the cardiac nerves were intact, histamine produced a decrease in heart rate. However, in the denervated animals, there was a slight increase in heart rate. 6 Inotropic responses to histamine in the blood pressure controlled groups were less variable than when blood pressure was uncontrolled. In all of these animals there was an increase in contractility, the increase being more marked in the denervated group. 7 The H2-receptor agonist impromidine produced a positive inotropic action in intact animals with uncontrolled blood pressure. PMID- 2890396 TI - Genito-urinary anomalies in arthrogryposis multiplex congenita. PMID- 2890397 TI - Transplantation of hematopoietic stem cells (HSC). PMID- 2890398 TI - Ten centre trial of artificial surfactant (artificial lung expanding compound) in very premature babies. Ten Centre Study Group. AB - A protein free artificial surfactant (artificial lung expanding compound; ALEC) composed of dipalmitoylphosphatidylcholine and phosphatidylglycerol was assessed for its effect on the main complications of prematurity in a prospective two stage randomised trial of 328 unselected babies delivered at between 25 and 29 weeks of gestation. Babies were randomised to receive approximately 100 mg artificial surfactant suspension or 1 ml saline. This was given at birth into the pharynx with up to three more endotracheal doses if the baby was intubated during the first day. Treatment with artificial surfactant reduced the neonatal mortality from 27% to 14%, the incidence of parenchymal brain haemorrhages from 24% to 16%, and the severity of the respiratory distress syndrome. In the first 10 days babies treated with artificial surfactant who survived averaged 19 hours less in greater than 30% oxygen, 20 hours less ventilation, and 17 hours less supplemental oxygen. Artificial surfactant had no effect on the incidence of pneumothoraces, pulmonary interstitial emphysema, patent ductus arteriosus, or postnatal infections and no serious side effects. Artificial surfactant (ALEC) given to very premature babies at birth significantly reduces their mortality and the respiratory support needed and should prove a valuable addition to treatment. PMID- 2890399 TI - From whom do children catch pertussis? PMID- 2890400 TI - Undescended testes in low birthweight infants. PMID- 2890402 TI - Changes in renal functions during beta-blocker carazolol administration in acute heat-stressed pigs. PMID- 2890401 TI - Membrane phenotype and response to deoxycoformycin in mature T cell malignancies. AB - The adenosine deaminase inhibitor deoxycoformycin was used in low doses to treat 19 patients with clinically aggressive T cell malignancy with a mature membrane phenotype. The patients comprised eight with prolymphocytic leukaemia, two with chronic lymphocytic leukaemia, four with adult T cell leukaemia-lymphoma, three with Sezary syndrome, and two with T cell lymphoma. Two thirds of the patients had been resistant or minimally responsive to combination chemotherapy. Complete remission was obtained in five patients (two with prolymphocytic leukaemia and one each with chronic lymphocytic leukaemia, adult T cell leukaemia-lymphoma, and Sezary syndrome) and partial remission in two others. Unmaintained complete remission lasting more than one year was seen in three patients. Responses were obtained only in patients with CD4+,CD8-membrane markers (seven out of 10), and no responses were recorded in any of the nine patients with a different phenotype. In this series remission appeared to correlate with the membrane phenotype of the neoplastic cell and not with the cytopathological diagnosis. Future studies should establish the biochemical basis for the greater sensitivity of CD4+ lymphoid cells to deoxycoformycin. PMID- 2890403 TI - Excitatory and inhibitory effects of dopamine on neuronal activity of the caudate nucleus neurons in vitro. AB - Effects of dopamine on the rat caudate nucleus neurons were examined in a slice preparation using an intracellular recording technique. Perfusion of the bath with a low concentration (1 microM) of dopamine produced a depolarization concomitant with an increase in the spontaneous firing and the number of action potentials evoked by a depolarizing pulse applied into the cells. In contrast, higher concentrations (100-500 microM) of dopamine inhibited the spontaneous and current-induced firings without apparent effects on the resting membrane potential. In addition, during application of a high concentration (100 microM) of dopamine there was a marked elevation of the threshold potential of the action potential elicited by a higher depolarizing current. Simultaneous application of haloperidol (0.5-5 microM) antagonized both excitatory and inhibitory effects induced by the low and high concentrations of dopamine, respectively. In addition, the excitatory effect induced by a low concentration (1 microM) of dopamine was antagonized by domperidone (0.5 microM), a selective D2 receptor antagonist, while the inhibitory effect by a high concentration (100 microM) was blocked by SCH 23390, a selective D1 receptor antagonist. These results strongly suggest that the postsynaptic sites of caudate nucleus neurons have at least two subtypes of dopamine receptors (D1 and D2 receptors) that mediate inhibitory and excitatory responses of the neuron to dopamine, respectively. PMID- 2890404 TI - Norepinephrine in the interpeduncular nucleus of the rat: normal distribution and the effects of deafferentation. AB - We used correlative biochemical and histochemical methods to examine (1) the norepinephrine (NE) projection from the paired locus coeruleus (LC) to the midline interpeduncular nucleus (IPN) of the adult rat and (2) the ability of the LC to respond to denervation of their target following removal of noradrenergic afferents (6-hydroxydopamine lesions of the LC) or non-noradrenergic afferents (lesion of the paired fasciculi retroflexi(FR]. Histofluorescence revealed that the NE innervation from the two LC to the IPN is symmetric and overlapping. This projection is confined to rostral, central, and intermediate subnuclei and is absent from lateral and dorsal subnuclei. We found no evidence for homotypic collateral sprouting of undamaged LC neurons into the IPN following unilateral LC lesion. Bilateral LC lesions also did not induce sprouting by NE-containing neurons from other systems (e.g. the superior cervical ganglion or the lateral tegmental group) or from those LC neurons that survived the 6-hydroxydopamine lesion. Histofluorescence following bilateral FR lesions confirmed an earlier observation that apparent hyperinnervation of the IPN by LC afferents is elicited following removal of non-noradrenergic afferents. Measurements of the turnover rate of NE in the IPN of control animals and those that received bilateral FR lesions indicate an increased NE content and increased turnover rate of NE in the IPN of lesioned animals. Taken together these results suggest an increased number of NE terminals and an increase in the activity of tyrosine hydroxylase. No change in NE content or turnover rate was seen in the frontal cortex from these same animals. This is consistent with a target-dependent regulation of heterotypic collateral sprouting. PMID- 2890405 TI - Hippocampal cells primed with quisqualate are depolarized by AP4 and AP6, ligands for a putative glutamate uptake site. AB - The glutamate analog 2-amino-4-phosphonobutyrate (AP4), which in control slices has little effect on Schaffer synaptic responses in hippocampal area CA1, reduces Schaffer responses in slices treated with quisqualate. We have shown that this effect of AP4 is associated with depolarization of CA1 neurons and a persisting small reduction in Schaffer response amplitude. 2-Amino-6-phosphonohexanoate also depressed Schaffer responses following priming with quisqualate, but 2-amino-7 phosphonoheptanoate did not. Treatment with alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionate (AMPA) or N-methyl-D-aspartate (NMDA) did not sensitize slices to AP4. The pharmacology of this 'priming effect' of quisqualate corresponds to that of a putative uptake site. We suggest the effects of AP4 (and AP6) result from exchange for previously accumulated quisqualate. PMID- 2890406 TI - Cellular localization of soluble and membrane-bound forms of arylsulfatase in rat brain. AB - The cellular localization of the soluble and membrane-bound forms of the enzyme, arylsulfatase (ArS), in rat brain was investigated by measuring their activities in rat striatum after unilateral lesioning with the neurotoxin, kainic acid. Membrane-bound ArS (C form of ArS) activity was found to increase after lesioning and the increase paralleled that of the astroglial marker enzyme, glutamine synthetase. Total soluble ArS (A and B forms of ArS) was shown to decrease on day 2 after the kainic acid injection but rapidly increase thereafter. When the two soluble forms of arylsulfatase were measured separately, the activity associated with the A form was found to initially decrease followed by a rapid increase in activity, whereas the activity of the B form of the enzyme increased over the entire duration of the experiment. These data suggest that the ArS-C and B form of arylsulfatase predominate in proliferating astroglial cells, whereas the A form of arylsulfatase is present both in neuronal cell bodies and astroglia associated with the rat striatum. PMID- 2890407 TI - Neurons in the area postrema are the only catecholamine-synthesizing cells in the medulla or pons with projections to the rostral ventrolateral medulla (C1-area) in the rabbit. AB - We have identified, in the rabbit medulla and pons, neurons which project to the C1-region of the rostral ventrolateral medulla. By combining tyrosine hydroxylase immunohistochemistry with retrograde transport of Fluoro-Gold we determined whether any of the retrogradely labelled neurons synthesize catecholamines. The only doubly labelled cells were located in the area postrema. No other group of catecholamine-synthesizing neurons in either the medulla or the pons was found to project to the C1-area of the rostral ventrolateral medulla. Pharmacological agents which lower arterial pressure by stimulating adrenoceptors in the rostral ventrolateral medulla may act on receptors which are not innervated by catecholamine-synthesizing perikarya located outside the C1-region. PMID- 2890408 TI - A possible neurotransmitter role for CGRP in a hair-cell sensory organ. AB - We report that calcitonin gene-related peptide (CGRP) increases the discharge rate of afferent fibers innervating hair cells in the lateral line organ of Xenopus laevis. We have localized CGRP-like immunoreactivity in small, presumably efferent, fibers innervating the lateral line organ. In addition to providing evidence for a neurotransmitter role for CGRP in a sensory system, these results may help explain the non-cholinergic excitatory effect seen with efferent stimulation in this and other hair cell organs such as the inner ear. PMID- 2890409 TI - Voltage-dependency of the responses of cerebellar Purkinje cells to excitatory amino acids. AB - The voltage-dependency of the responses of Purkinje cells to excitatory amino acids was examined in rat cerebellar slices, using intrasomatic recordings with the single electrode voltage-clamp. In standard perfusion medium, the depolarizations evoked in these neurones by ionophoretic pulse applications (less than 300 ms) of L-glutamate, L-aspartate and quisqualate in their dendritic fields had underlying inward currents which did not increase or even decreased, as the holding potential was shifted to values more negative than -65 mV. This 'abnormal' voltage-dependency was still present in Mg2+ -free solution but was abolished in the presence of CsCl2 (10 mM) in the perfusion medium. When TTX (5 microM) and CdCl2 (0.1 mM) were further added to the bath in order to block regenerative conductances, thus broadening the range of the clamp voltages to more positive values than -50 mV, the current-voltage relation between -80 and 0 mV for responses to L-glutamate and L-asparate was almost linear. Our results support the view that low doses of both amino acids act on Purkinje cells essentially via the activation of receptors which are not of the N-methyl-D aspartate type. PMID- 2890410 TI - Quinolinate is a weak excitant of cortical neurons in cell culture. AB - Defined concentrations of quinolinate (QUIN) were administered to murine cortical neurons in culture impaled for intracellular recording. In physiological recording medium containing 1 mM Mg, concentrations of QUIN up to 2 mM had minimal effect on membrane potential and input resistance; only at higher concentrations did QUIN produce consistent depolarizations, which were accompanied by apparent increases in membrane resistance. In the absence of Mg, responses to QUIN were larger and were accompanied by decreases in membrane resistance, but QUIN was still a weak neuroexcitant, exhibiting an ED50 of greater than 1 mM. Phthalic, dipicolinic and nicotinic acids, structural analogues of QUIN, were even less potent neuroexcitants. The relationship between QUIN depolarization amplitude and membrane potential was linear in the absence of Mg, but in the presence of 1 mM Mg showed a non-linearity consistent with the voltage-dependent Mg block of N-methyl-D-aspartate (NMDA) receptor-mediated responses described by others. QUIN responses had a marked dependence on the presence of extracellular Na, and an extrapolated reversal potential of +12 mV, consistent with the large involvement of an Na influx. The responses were attenuated by the selective NMDA receptor antagonists, DL-2-amino-5 phosphonovalerate and ketamine, as well as by the broad spectrum antagonist kynurenate, but not by L-glutamate diethylester or gamma-D-glutamylaminomethyl sulfonate, compounds reported to block quisqualate or kainate receptors. The present study is consistent with the suggestion of other workers that QUIN neuroexcitation is mediated in large part by an Na influx through cation permeable NMDA-activated channels, but provides new quantitative data suggesting that the potency of QUIN as a cortical neuroexcitant is low. This low potency may argue against a role for QUIN as a traditional fast excitatory neurotransmitter. PMID- 2890411 TI - Glutamate-induced ionic currents in cultured neurons from the rat superior colliculus. AB - The ionic currents induced in cultured rat superior colliculus neurons by rapid application of glutamate (Glut) and the glutamate receptor agonists quisqualate (Quis) and N-methyl-D-aspartate (NMDA) were examined using the whole-cell patch clamp technique. Dissociated cell cultures consisting exclusively of superficial gray layer neurons from rats aged E21-P2 were used. After 7-10 days in vitro, all neurons responded to Glut and the selective agonists, NMDA and Quis. Glut was a mixed agonist, and a variable fraction (10-100%) of Glut-activated currents was due to involvement of NMDA receptors. The NMDA response was strongly regulated by extracellular Ca and Mg levels and modified by exposure to Quis. Quis transiently removed the block of NMDA-activated currents by D-amino-phosphonovaleric acid (APV). PMID- 2890412 TI - Extensive co-existence of neuropeptides in the rat visual cortex. AB - The peroxidase-antiperoxidase immunohistochemical technique has been used to examine the co-existence of peptides within individual neurons of the rat visual cortex. Pairs of consecutive paraffin sections were stained alternately for 2 of the 4 peptides: somatostatin (SRIF), vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK) and neuropeptide Y (NPY). Analysis revealed the co existence of SRIF with VIP, CCK and NPY and between VIP and CCK. These results show that the co-localization of neuropeptides in cortical neurons is more widespread than previously demonstrated. PMID- 2890413 TI - Development of spontaneous and glutamate-evoked activity is altered by chronic ethanol in cultured cerebellar Purkinje neurons. AB - The effects of continuous exposure to ethanol on the cytological and physiological development of a central nervous system (CNS) neuron were studied using the cultured Purkinje neuron of the rat cerebellar cortex. Purkinje neurons in fetal rat brain cultures which are established at one day before birth show development comparable to that described in vivo in other studies. In culture, Purkinje neurons progress from immature rounded cells with fine neurites to mature neurons with a branched dendritic structure. These structural changes are accompanied by an increase in the duration and complexity of the excitatory response to glutamate, by transitions in the patterns of spontaneous activity, and by an increase in mean firing rate. Our results demonstrate that chronic exposure to a low concentration of ethanol (90 mg%; 19.5 mM) during development selectively alters the electrophysiological but not the morphological properties of Purkinje neurons. Specifically, ethanol treatment reduces the responsiveness of these neurons to glutamate, delays the expected developmental transitions in patterns of spontaneous activity, and induces increased spontaneous bursting activity, particularly at the stage of dendritic formation. Impairment of responsiveness to glutamate is significant in that it may reflect the compromise by ethanol of a major excitatory pathway in the cerebellar cortex, resulting from the decreased efficacy of glutamatergic input from parallel fibers. In contrast to the results of other studies using adult neurons as a model for the effects of ethanol, our work suggests that the developing CNS neuron does not become tolerant; that is, in the continuing presence of ethanol, it does not express physiological function equivalent to that of the control. PMID- 2890414 TI - Neural membrane glycoproteins associated with chicken Thy-1: an anti-idiotypic antibody study. AB - In order to investigate the possible binding of Thy-1 to other neuronal cell surface proteins, anti-idiotypic antibodies were raised using a panel of anti-Thy 1 monoclonal antibodies. Anti-idiotypic antibodies were selected for their ability to bind to day-old chick brain membrane components in enzyme-linked immunosorbent assays (ELISA), and to bind to membrane glycoproteins as determined by Western transfer immunoblotting assays. The 5 monoclonal anti-idiotypic antibodies bind to a membrane glycoprotein component of 70 kDa, and one of the antibodies also binds to 3 higher molecular weight components of 160 kDa, 120 kDa and 90 kDa. These antibodies bind to areas of the chicken cerebellum known to be rich in Thy-1. It is postulated that these molecules are associated with Thy-1, and that the role of Thy-1 on the neuronal cell surface, may be to form complexes with, and/or to stabilise these higher molecular weight glycoproteins during synaptic development. PMID- 2890415 TI - Intrathecal N-methyl-D-aspartate (NMDA) activates both nociceptive and antinociceptive systems. AB - Injection of the excitatory amino acid N-methyl-D-aspartate (NMDA) into the spinal subarachnoid space of rats produces both hyperalgesic and analgesic effects. At lower concentrations (0.5 mM) little behavioral effect is elicited by the drug. However, brief hyperalgesia followed by several minutes of analgesia can be detected in these animals. Higher concentrations of the drug produce vocalization, caudally directed scratching and biting and hyper-responsiveness to light touch. The NMDA antagonist, arginine vasopressin, produces analgesia when injected by itself and completely reverses all effects of NMDA. NMDA-induced analgesia, but not hyperalgesia, is reversed by intrathecal administration of naloxone, methysergide and phentolamine. The analgesic effects of both agonist and antagonist are markedly potentiated by spinalization. These results suggest the involvement of NMDA receptors in both the transmission of pain and the mediation of spinal segmental pain inhibitory mechanism. PMID- 2890416 TI - Neuropeptides mark functionally distinguishable cholinergic enteric neurons. AB - Subpopulations of physiologically identified cholinergic enteric neurons in cell culture contain somatostatin (SOM)- or vasoactive intestinal peptide (VIP)- like immunoreactivity (LIR). These subpopulations differ in their synaptic effects on other neurons: cholinergic neurons that contain SOM-LIR cause fast nicotinic excitatory postsynaptic potentials (EPSPs) that have significantly larger amplitudes than do EPSPs caused by cholinergic neurons that lack SOM-LIR. Cholinergic neurons containing VIP-LIR cause slow non-cholinergic depolarizations in addition to fast nicotinic EPSPs. These findings are the first correlation between neuropeptide content and functional differences in the synaptic effects of subpopulations of cholinergic enteric neurons. PMID- 2890417 TI - Sex steroid effects on extrahypothalamic CNS. I. Estrogen augments neuronal responsiveness to iontophoretically applied glutamate in the cerebellum. AB - The purpose of this study was to test whether 17 beta-estradiol (E2) could alter neuronal activity or responsiveness to iontophoretically applied amino acid neurotransmitters in an area not reported to contain classical E2 receptors. Such a region is the cerebellum, which was selected as a model system for these studies because it has been well characterized electrophysiologically. Extracellular activity of cerebellar Purkinje neurons was recorded from urethane anesthetized, adult, ovariectomized rats using multibarrel glass micropipets. Spontaneous firing rate and responses of single units to microiontophoretic pulses (10 s pulses every 40 s) of GABA (10-50 nA) or glutamate (GLUT, 3-40 nA) were examined before, during and after iontophoretic (0.25 mM 17 beta-estradiol hemisuccinate) or jugular i.v. (100, 300 or 1000 ng/kg 17 beta-estradiol) administration of E2. Both modes of E2 administration resulted in a significant increase in Purkinje cell excitatory responses to GLUT, independent of the direction of change in spontaneous firing rate. This effect was seen as early as one minute after iontophoretic application of E2 and 10-40 min following i.v. E2. In all cases, recovery to the control level of response was not observed by 2 h following E2 administration. 17 alpha-E2 (300 ng/kg) resulted in a less pronounced, transient increase in GLUT response, while a lower dose (100 ng/kg) did not have any effect. Prior administration of the anti-estrogen tamoxifen did not prevent any of the observed E2 effects. In addition, estrogen-priming did not alter E2-induced potentiation of GLUT responses. In contrast to the effect of E2 on GLUT responsiveness, GABA-mediated inhibition of Purkinje cells was either increased, antagonized or unchanged following E2 application. In summary, this study suggests the hypothesis that circulating levels of E2 may alter neuronal sensitivity to specific neurotransmitter substances within the cerebellar circuitry. PMID- 2890418 TI - Sex steroid effects on extrahypothalamic CNS. II. Progesterone, alone and in combination with estrogen, modulates cerebellar responses to amino acid neurotransmitters. AB - In a preliminary report we have shown that both intravenous and local application of progesterone (P) are capable of increasing cerebellar Purkinje cell responsiveness to microiontophoretically applied gamma-aminobutyric acid (GABA) and decreasing responsiveness to glutamate (GLUT) in the urethane-anesthetized, ovariectomized adult rat. In the present study we have examined the time course of effects of several doses of P and different combinations of both E2 and P on responses of individual Purkinje cells to GABA and GLUT. Extracellular activity of single Purkinje neurons was recorded using multibarrel glass micropipets. Spontaneous firing rate and responses of neurons to microiontophoretic pulses (10 s pulses every 40 s) of GABA (10-50 nA) and GLUT (3-40 nA) were examined before and after jugular i.v. administration of P or E2/P combinations to ovariectomized rats. In some cases animals received s.c. injections of E2 (2 micrograms) at 24 and 48 h before the day of recording. This injection schedule results in maximal reproductive effects of P. Within 5-15 min after P administration (5,50 or 500 micrograms) to ovariectomized rats, Purkinje cell responses to GLUT were decreased by 87%, and inhibitory responses to GABA were increased by 50%, with no associated change in spontaneous firing rate. In addition, the magnitude of the change in amino acid response was directly proportional to the dose of P. In most cases, complete recovery was observed 20-45 min after P administration. E2 pretreatment did not alter these P-induced effects. Combinations of E2 (300 ng/kg) and P (50 or 500 micrograms) injected simultaneously resulted in effects on GLUT responsiveness which were similar to those seen with P alone, while effects similar to E2 alone were observed with administration of E2 plus P at 5 micrograms. The administration of a protein synthesis inhibitor, anisomycin (30 mg/kg, i.v.), 20 min before the recording session did not prevent any of the above steroid effects. These results indicate that sex steroids can act to alter neuronal responsiveness to putative neurotransmitters in a CNS region not known to contain steroid receptors and that the particular combination of steroids will determine the neuronal response. These findings further suggest that the observed steroid-induced alterations in Purkinje cell responsiveness do not appear to require genomic mechanisms. PMID- 2890419 TI - Effect of D890 on membrane properties of neocortical neurons. AB - D890, a derivative of the Ca2+ channel antagonist D600, was intracellularly applied from conventional microelectrodes into pyramidal neurons of neocortical slices. The effects of D890 were ascertained by evaluating alterations in membrane properties following drug administration and by comparing these neurons to untreated controls. The amplitude of action potentials (APs) evoked by depolarizing current pulses was attenuated by up to 30% within about 15 min after impalement with D890-containing electrodes. AP rate of rise was reduced by up to 80% and duration was increased. These effects were dependent upon the rate of stimulation. When depolarizing pulses were delivered at low rates of stimulation (e.g. 0.1 Hz), the overshoot of evoked APs declined by about 10%. At higher frequencies (greater than 2 Hz) the AP overshoot decreased by up to 90%. These effects were mostly reversible on decreasing the frequency of stimulation. A half maximal effect was attained at about 1 Hz, when APs of control neurons were unaltered. In neurons impaled with D890-containing electrodes, depolarizing current pulses delivered in the presence of tetraethylammonium (TEA) and tetrodotoxin elicited high threshold calcium spikes which had a duration between 20 and 200 ms. In the early phase of D890 application, the duration of Ca2+ spikes decreased in a reversible frequency-dependent manner; after prolonged application, however, the recovery was incomplete. On the average, Ca2+ spike amplitude and duration decreased by 20% and 50%, respectively, suggesting that D890 usually produces an incomplete blockade of the underlying CA current. The duration of the slow envelope of orthodromically evoked epileptiform paroxysmal depolarizing shifts (DSs), induced by bath application of 10(-5) M bicuculline, was frequency dependent and consistently increased from about 20 ms to 150 ms (half amplitude width) at frequencies above 0.5 Hz. In the presence of D890, the action potentials superimposed on the slow envelope of the DS were attenuated, but neither the amplitude nor the frequency-dependent progressive prolongation of the DS was altered. Application of TEA in the presence of bicuculline (10(-5) M) increased the amplitude and duration of the DS in neurons impaled with D890 containing electrodes. Under these conditions, the durations of DSs evoked by low frequency orthodromic stimulation (greater than 0.5 Hz) were still progressively prolonged, while, in the same neuron, directly evoked Ca2+ spikes progressively decreased in amplitude and duration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2890420 TI - Antibodies to dynorphin A(1-13) but not beta-endorphin inhibit electrically elicited feeding in the rat. AB - Highly specific antibodies to dynorphin A(1-13), infused into the lateral ventricle, elevated brain stimulation threshold for eliciting feeding behavior. Antibodies to beta-endorphin had little or no effect. Temporal analysis of the anorectic action indicated a striking similarity to the effect of systemically administered naloxone. These findings suggest that central dynorphin is involved in the control of ingestive behavior and that the anorectic action of naloxone may result from antagonism of dynorphinergic transmission. PMID- 2890422 TI - Ontogeny of somatostatin-like immunoreactivity in the human fetus and infant spinal cord. AB - The localization and distribution of somatostatin like-immunoreactivity (SSLI) in postmortem human fetus and infant spinal cord and dorsal root ganglia were studied by using the indirect immunofluorescence technique. SSLI, which was mostly located within varicose fibers and terminal-like structures, occasionally within cell bodies, was detected during early fetal life (on gestational week 9 and beyond). The changes occurring from the early to the late fetal and infant stages mainly resulted in a progressive increase in the number of somatostatin like immunoreactive fibers within most of the gray areas. On the whole the majority of immunolabelled fibers and terminal-like structures were observed over the superficial layers of the dorsal gray including the marginal zone and the substantia gelatinosa. Other regions displaying a moderate number of somatostatin like immunoreactive fibers were the intermediate gray and the gray commissure area around the central canal. A few scattered immunofluorescent fibers were unevenly distributed over the white matter especially in the lateral and ventral funiculus areas and near the ventral motor nuclei. A few somatostatin-like immunoreactive cell bodies were occasionally found in the superficial layers of the dorsal gray and in the intermediolateral gray. Immunolabelled cells were further usually visualized in dorsal root ganglia. Although the distribution patterns of somatostatin-like immunoreactive structures were similar throughout the entire spinal cord, the highest density of immunolabeled fibers, however, was seen at the lumbosacral level. Our results indicate that in the human spinal cord SSLI is already widespread before birth. It is further suggested that somatostatin ontogenesis in human spinal cord and dorsal root ganglia begins early in fetal life. PMID- 2890421 TI - Interaction between enkephalin and dopamine in the avian retina. AB - Biochemical and pharmacological techniques were utilized to investigate the interaction between the enkephalinergic and dopaminergic systems in the chicken retina. Exogenously applied enkephalin and its analogues were observed to inhibit the release of preloaded dopamine from the retina. This inhibition was concentration-dependent and was suppressed by the opiate antagonist, naloxone. The relationship between enkephalinergic and dopaminergic amacrine cells was studied in retinas which were subjected to 6-hydroxydopamine (6-OHDA) treatments. 6-OHDA degenerated approximately 80-90% of those cells which exhibit high affinity uptake of [3H]dopamine. In 6-OHDA-treated retinas, the capacity of 3H labelled [D-Ala2]methionine enkephalinamide to bind specifically to opiate receptors was substantially reduced (only 70-75% of the control). Scatchard analyses and ligand displacement studies indicated that this decrease in binding was due to a reduction in the number of opiate receptors. Taken together, these observations strongly indicate that a fraction of the opiate receptors in the chicken retina (25-30%) are closely associated with the population of dopaminergic amacrine cells. PMID- 2890423 TI - Clinical perspectives of beta-carbolines from first studies in humans. AB - First results from studies in healthy subjects with the beta-carbolines ZK 91 296, ZK 95 962 and ZK 93 426 are reviewed. ZK 91 296 and ZK 95 962, characterized as partial benzodiazepine agonists in preclinical research, were unable to induce some typical benzodiazepine effects like sedation when administered intravenously in high doses. ZK 95 962, reported to be effective in photoepileptic patients, was able to reverse lormetazepam-induced sleep as documented by EEG-parameters. The benzodiazepine receptor antagonist ZK 93 426 dose-dependently elicited alertness, restlessness and mild apprehension--symptoms opposite those known for the benzodiazepines. The activating effect of ZK 93 426 was confirmed by the results from e.g., self-rating scales and the logical reasoning test. In another placebo-controlled study comparing the effects of ZK 93 426 alone and in combination with lormetazepam vigilosomnograms obtained after ZK 93 426 alone clearly confirmed the activating effect. In combination with lormetazepam ZK 93 426 was able to reverse the benzodiazepine induced sleep. The attenuation of benzodiazepine effects was also evident from multiple sleep latency tests. Our results support findings from animal experiments which classify these beta carbolines as benzodiazepine receptor ligands with partial agonist and antagonist properties. beta-Carbolines may prove to be beneficial drugs in the treatment of anxiety, convulsions and diseases with an impairment of cognitive functions as well as in the reversal of unwanted benzodiazepine effects. PMID- 2890424 TI - [The effect of local anesthetics and beta adrenolytics on the fluidity of lipids and biological membranes]. PMID- 2890425 TI - Anatomy and pathology of the basal ganglia. AB - Neurotransmitters of the basal ganglia are of three types: I, amino acids; II, amines; and III, peptides. The amino acids generally act ionotropically while the amines and peptides generally act metabotropically. There are many examples of neurotransmitter coexistence in basal ganglia neurons. Diseases of the basal ganglia are characterized by selective neuronal degeneration. Lesions of the caudate, putamen, subthalamus and substantia nigra pars compacta occur, respectively, in chorea, dystonia, hemiballismus and parkinsonism. The differing signs and symptoms of these diseases constitute strong evidence of the functions of these various nuclei. Basal ganglia diseases can be of genetic origin, as in Huntington's chorea and Wilson's disease, of infectious origin as in Sydenham's chorea and postencephalitic parkinsonism, or of toxic origin as in MPTP poisoning. Regardless of the etiology, the pathogenesis is often regionally concentrated for reasons that are poorly understood. From studies on Parkinson and Huntington disease brains, evidence is presented that a common feature may be the expression of HLA-DR antigen on reactive microglia in the region where pathological neuronal dropout is occurring. PMID- 2890426 TI - Motor, behavioral and pharmacologic findings in Tourette's syndrome. AB - We studied 112 patients with Tourette's syndrome (TS); the male-to-female ratio was 3.8, the mean age of onset was 7.3 years, and the average duration of symptoms prior to the initial evaluation was 15.2 years. Seventy-nine percent of the patients had at least one family member with motor or vocal tics, and an additional 10 percent had a family member with marked obsessive-compulsive behavior. Simple motor tics occurred as the presenting symptom in about one-third of patients; one-third had multiple motor tics at the onset, and another third started with vocal tics. During the course of the illness all patients developed multifocal motor tics and 86 percent had vocal tics. Verbal and mental coprolalia was present in 44 percent of the patients. Copropraxia was seen in 19 percent of patients, and both coprolalia and copropraxia were more frequent among the males than expected. Attentional deficit disorder was diagnosed in 36 percent of the patients and 32 percent had obsessive-compulsive personality. Sleep disturbances were reported by 62 percent of the patients and polysomnographs in 34 patients showed motor and vocal tics during all stage of sleep, sleep apnea, abnormal arousal pattern, and other sleep disturbances. Patients with mild symptoms improved with clonidine or clonazepam, but those with more advanced disorder required fluphenazine, pimozide, haloperidol or tetrabenazine. PMID- 2890427 TI - Magnetic resonance imaging of the foot and ankle. AB - Magnetic resonance imaging enhances the inherent differences in the density of tissues to allow the diagnosis of pedal disorders not readily observed by other diagnostic means. The technique is particularly useful for the evaluation of the nature and extent of soft tissue pathology. In addition, certain osseous and joint disorders, such as osteomyelitis and Sudeck's atrophy, may be detected in their incipient stages. PMID- 2890429 TI - Cerebral vasculitis associated with hairy cell leukemia. AB - Hairy cell leukemia was diagnosed in a 74-year-old man. He was followed for 5 years when he developed confusion and focal neurological signs. Despite investigation and treatment he died. Postmortem study revealed isolated primary necrotizing vasculitis affecting the cerebral arteries. No leukemic infiltration of the central nervous system was found. There is a recognized association between hairy cell leukemia and generalized necrotizing vasculitis of polyarteritis type, however, this is the first case report of isolated cerebral vasculitis associated with this condition. The importance of excluding infective (mycotic) arteries in this type of case is emphasized. PMID- 2890428 TI - 2'-Deoxycoformycin therapy in adult T-cell leukemia/lymphoma. AB - Six Caribbean patients with histologically and immunologically characterized adult T-cell leukemia/lymphoma (ATL) were treated intravenously (IV) with 2' deoxycoformycin (DCF) at a dose of 5 mg/m2 on days 1, 2, 8, 15, and 22 with four additional weekly doses to convert any partial responses (PR) to complete responses (CR). Patients were considered eligible for this study if refractory to or relapsed from combination chemotherapy, had a life expectancy of 4 weeks or more, a performance status greater than or equal to 50%, normal renal and hepatic function, and no chemotherapy within 4 weeks. Clinical characteristics of the patients in this study included lymphadenopathy in five patients, skin involvement in four patients, bone marrow infiltration in five patients, and central nervous system involvement in two patients. Circulating ATL cells were present in four patients, and three were hypercalcemic. Of five patients evaluable for response, there was one PR of 1 month, and two minor responses lasting 2 and 3 weeks. The median duration of survival for all treated patients was 3 weeks or more. The DCF was associated with moderate side effects, including conjunctivitis in three patients, nausea and vomiting in two patients, progressive hepatic insufficiency in one patient, and moderate myelotoxicity in three patients. Infections occurred in four patients, including two cases of oral candidiasis and two cases of fatal neutropenic sepsis in patients receiving concurrent intrathecal methotrexate. As a single agent, DCF appears to have limited activity in advanced refractory/relapsed ATL. Studies in the future should explore DCF in combination with other cytotoxic agents as initial therapy in better-risk patients. PMID- 2890431 TI - Characterization of a mammary carcinoma elaborated factor stimulating gamma glutamyltranspeptidase expression in bone marrow cells. AB - The elevation of bone marrow gamma-glutamyltranspeptidase (GGT) and alkaline phosphatase (AP) content in rats carrying mammary carcinoma 5A (MC), reproduced in a short-term (48-h) liquid culture of normal bone marrow cells, was found to be attributable to a blood-borne protein factor with an apparent molecular weight of 60,000. Partial purification, based on the extent of stimulation of GGT expression in this culture, increased the specific activity of the host serum from 1.5 to 40 units and that of MC extracts from 6 to 560 units. Production of the factor by MC in vitro, however, resulted in specific activities of 3000 units in the conditioned medium, and a further 60-fold purification was achieved by DEAE-cellulose, Sephadex G-100, and hydroxylapatite chromatography. The chemical characteristics of the MC-elaborated protein indicate nonidentity to previously isolated colony formation stimulating factors which also induced GGT (and AP) expression by rat bone marrow cells. Most of the AP inducing ability of the MC serum and MC-conditioned medium copurified with and was still present in preparations with the highest specific activity vis a vis GGT. In mouse (instead of rat) bone marrow cells, however, no AP response accompanied the stimulation of GGT expression by MC (or colony formation stimulating factor) preparations. PMID- 2890430 TI - Phenotypically selective promotion of diethylnitrosamine-initiated altered hepatocyte foci by dietary phenobarbital or a topically applied coal-derived organic mixture in male and female rats. AB - Relative frequencies of diethylnitrosamine (DEN)-initiated foci of altered hepatocytes appearing in response to promotion by either dietary phenobarbital or a topically applied coal-derived organic mixture (CDM) were investigated in male and female rats. The focus population was examined for two histochemical markers, elevated gamma-glutamyl transpeptidase [GG(+)] and iron exclusion [FE(-)], giving rise to 3 detectable focus phenotypes, i.e., GG(+) foci, FE(-) foci, and GG(+)/(FE(-) foci. Frequencies of the 3 phenotypes were quantitated through the use of serial frozen sectioning and computer-assisted image analysis. In agreement with our prior observations, cutaneous exposure to CDM or dietary phenobarbital promoted the expression of DEN-initiated foci. However, the current data showed that this promoting effect of CDM occurred only in females and was restricted to foci with the GG(+)/FE(-) phenotype. Dietary phenobarbital, on the other hand, promoted both the GG(+) and GG(+)/FE(-) phenotypes and was effective in both males and females, although a sex-related differential in the promoting efficiency of phenobarbital was also observed. The pronounced heterogeneity in the responses of the 3 focus phenotypes suggests that each phenotype is the consequence of a specific type of genomic alteration with a specific capacity to undergo phenotypic expression in response to a given promoting stimulus. PMID- 2890432 TI - Reciprocal cross-resistance in human rhabdomyosarcomas selected in vivo for primary resistance to vincristine and L-phenylalanine mustard. AB - Primary resistance to vincristine (VCR) has been selected in rhabdomyosarcoma xenograft HxRh12 by sequential administration of VCR at 1.5 and subsequently 3 mg/kg/passage. The resistant tumor (HxRh12/VCR-3) was approximately 4-fold resistant to VCR and resistance was stable in the absence of selecting pressure (greater than 2 yr). HxRh12/VCR-3 was 2- to 3-fold cross-resistant to L phenylalanine mustard (L-PAM) but only slightly cross-resistant to ifosfamide. To determine whether selection for primary resistance to L-PAM conferred cross resistance to VCR we selected an L-PAM-resistant subline of rhabdomyosarcoma xenograft HxRh28 (HxRh28/L-PAM-13). This tumor was 2- to 3-fold resistant to L PAM and 3-(p-fluorophenyl)-L-alanyl-3-[m-bis-(2-chloroethyl)-aminophenyl]-L- alanyl-L-methionine ethoxyhydrochloride, cross-resistant to cyclophosphamide and ifosfamide, and completely resistant to VCR under in vivo conditions. Pharmacokinetic studies in HxRh12/VCR-3 showed decreased retention of [G-3H]VCR but not alteration in metabolism. Expression of mdr1, a gene that encodes P glycoprotein, associated with the multiple drug resistance phenotype, was examined. Expression of mdr1 was detected in both HxRh12 and HxRh28 tumors, sensitive to VCR, but there was no increase in expression in tumors selected for primary resistance to VCR or L-PAM. Data suggest that mechanisms other than those associated with "classical" multiple drug resistance confer resistance in these tumors. In clinical evaluation against childhood rhabdomyosarcoma, L-PAM has demonstrated only slight activity in patients relapsing on conventional therapy (including VCR) but demonstrated marked activity in patients with advanced previously untreated disease. It appears likely, therefore, that cross-resistance between VCR and L-PAM as demonstrated in this model may have clinical significance. PMID- 2890433 TI - Immunodetection and modulation of cellular growth with antibodies against native transforming growth factor-beta 1. AB - In an attempt to identify and quantitate latent and active forms of transforming growth factor beta (TGF beta) without the use of cell cultures and to test for autocrine stimulation by TGF beta, rabbit antibodies were raised against native human and porcine platelet-derived TGF beta. A radioimmunoassay for TGF beta was developed using radioiodinated TGF beta, anti-TGF beta antibodies, and protein A. Inhibition in the radioimmunoassay was achieved with nanogram quantities of TGF beta, comparable to the sensitivity of radioreceptor assays. Analyses of the TGF beta levels of conditioned medium from cultured cells indicated that the latent form(s) of TGF beta is not detectable in the radioimmunoassay established using antibodies raised against native TGF beta. Immunoprecipitation analysis of radiolabeled conditioned medium revealed a specific Mr 25,000 band only after acidification. A Mr 62,000 protein was observed with and without prior acidification of the medium but could not be competed with unlabeled TGF beta in the immunoprecipitation indicating antigenic unrelatedness. The anti-TGF beta IgG inhibited the binding of [125I]TGF beta to the cell surface receptors in a radioreceptor assay. TGF beta inhibition of A549 cell growth was reversed by the antibodies, which also neutralized the growth inhibitory effects of TGF beta on AKR-2B cells in a monolayer [3H]thymidine incorporation assay as demonstrated by prevention of TGF beta inhibition of insulin and epidermal growth factor stimulated DNA synthesis. The antibodies also effectively inhibited spontaneous soft agar growth of AKR-MCA fibroblasts, providing evidence for autocrine secretion of TGF beta as a mechanism of their anchorage-independent growth. PMID- 2890434 TI - Transforming growth factors. AB - The term transforming growth factor (TGF) has been applied to peptides that have the ability to confer the transformed phenotype on untransformed fibroblastic indicator cells in vitro. Peptides representing two distinct classes of TGFs have been purified to homogeneity. Type alpha and type beta TGFs are distinguished both chemically by their unique amino acid sequences and biologically by their different activities on cells. Type alpha TGFs are single chain peptides of 50-53 amino acids cross-linked by three disulphide bonds. They have strong homology to epidermal growth factor with which they compete for receptor binding. Type beta TGFs have a homodimeric structure comprised of two chains of 112 amino acids, each containing nine cysteine residues; TGF beta binds to a unique cell surface receptor. Type alpha TGFs are usually mitogenic for fibroblasts, whereas type beta TGFs have bifunctional effects on cell growth and can either stimulate or inhibit growth of the same cells, depending on conditions. The interactions of type alpha and beta TGFs can be either synergistic or antagonistic. Though the development of peptide antagonists to type alpha TGFs may have therapeutic potential for the treatment of malignancy, type beta TGFs may inhibit tumorigenesis. PMID- 2890435 TI - Interruption of systemic venous return with portal continuation: assessment using magnetic resonance imaging. AB - A case of interruption of both the superior and infrahepatic inferior vena cava with portal continuation of the systemic venous return is described. This unusual abnormality is probably acquired and represents the result of earlier, silent thrombosis of the venae cavae. Magnetic resonance imaging provided valuable anatomic information supplementing venography. PMID- 2890436 TI - Distinct prion proteins in short and long scrapie incubation period mice. AB - The Prn-i gene, controlling scrapie incubation period, is linked to or congruent with the murine prion protein (PrP) gene, Prn-p. In prototypic mouse strains with long (l/Ln) and short (NZW) incubation periods, Prn-p transcription is initiated at similar multiple sites. The predicted NZW and l/Ln PrP proteins differ at codons 108 and 189. Codon 189, highly conserved in mammals, lies within a polymorphic BstEll site that is retained in 17 mouse strains known to have short or intermediate incubation times, but is absent in l/Ln and two other inbred mice with long incubation times. Codon 108 in mice with short or intermediate incubation times encodes Leu; in mice with long incubation times it encodes Phe. The correlation of PrP sequence with length of scrapie incubation period suggests, but does not formally prove, congruency between Prn-p and Prn-i. PMID- 2890437 TI - The segmentation and homeotic gene network in early Drosophila development. PMID- 2890438 TI - A complex genetic locus, polyhomeotic, is required for segmental specification and epidermal development in D. melanogaster. AB - Two mutagenic events are required to make null mutations of polyhomeotic (ph), which suggests that the locus is complex. Amorphic mutations (ph degrees) die in mid-embryogenesis and completely lack ventral thoracic and abdominal epidermal derivatives, whereas single-event mutations lead to transformations similar to those of known dominant gain of function mutants in the Antennapedia and bithorax complexes. After a chromosomal walk, the ph gene was localized using deficiencies and ph mutations that result from DNA rearrangements. Hybridization analyses show that there are two large, duplicated sequences in the ph region, and DNA lesions affecting either one of these repeats alter the function of the ph locus. We propose a model that may account for this unusual functional organization. PMID- 2890439 TI - Synthesis of biologically active fibroblast-activating factor (FAF) by xenopus oocytes injected with T lymphocyte mRNA. AB - Activation of human peripheral blood T lymphocytes results in the production of fibroblast-activating factor (FAF), a mediator which stimulates fibroblast proliferation. This lymphokine, which may provide a molecular link between cell mediated immune reactions and fibroplasia, has been identified as a T-cell product both in vitro and in vivo. In order to study the mechanisms of synthesis and activity of FAF, poly(A) RNA was isolated from concanavalin A-stimulated T lymphocytes and injected into Xenopus oocytes. The injected oocytes translated the messenger RNA and produced a material with the biological and biochemical properties of human FAF. The oocyte product induced proliferation in serum-free quiescent fibroblast monolayers and exhibited the same molecular weight and charge as the T-cell-derived factor. Oocytes injected with poly(A)-RNA from unstimulated T lymphocytes produced little, if any, FAF activity. We conclude that activation of T lymphocytes enhances transcription of FAF mRNA as detected in the oocyte translation assay. This translated material has biological activity and biochemical characteristics consistent with FAF and is suitable for further studies on the expression and synthesis of FAF (poly)peptides. PMID- 2890440 TI - Biphasic binding of 125I-iodocyanopindolol to beta-adrenergic receptors in rat cerebral cortical membranes. I. Assessment by the use of agonists. PMID- 2890441 TI - [Treatment and care of complications of peritoneal dialysis in epidemic hemorrhagic fever]. PMID- 2890442 TI - Cardiovascular effects of non-depolarizing neuromuscular blockers in patients with aortic valve disease. AB - To compare haemodynamic responses associated with equipotent doses of neuromuscular blockers and high-dose fentanyl (50 micrograms.kg-1), 40 patients with aortic valve stenosis (AS) and 20 patients with aortic insufficiency (AI) were randomized to four study groups to receive the following: (1) pancuronium 0.12 mg.kg-1, (2) vecuronium 0.12 mg.kg-1, (3) atracurium 0.4 mg.kg-1, or (4) pancuronium-metocurine mixture (0.4 mg + 1.6 mg/ml): 1 ml/10 kg). Neuromuscular blockers were injected at the same time with the fentanyl; haemodynamics were recorded with the patients awake (baseline), at two minutes post-induction, and at two and five minutes after intubation. In patients with AS, pancuronium increased heart rate more than vecuronium or atracurium; heart rates were also higher with the pancuronium-metocurine mixture than with vecuronium. Although there were no ECG signs of ischaemia, one patient given pancuronium developed severe hypotension associated with tachycardia. Reductions in SVR after atracurium allowed small but significant (p less than 0.01) decreases in MAP which were well tolerated; one patient, however, did develop severe hypotension. Intubation resulted in significant (p less than 0.01) increases in MAP in the pancuronium-metocurine mixture group. Vecuronium permitted the most stable overall haemodynamic course at all measurement times. In contrast, patients with AI showed stable haemodynamics after vecuronium, pancuronium and the pancuronium metocurine mixture; one patient became tachycardic following vecuronium. Atracurium caused unexplained elevations in diastolic and mean arterial pressures which were significant when compared to vecuronium (p less than 0.01). These results in increases in PCWP; mean PA pressures and CVP were also increased. These effects of atracurium inpatients with Al need further evaluation. PMID- 2890443 TI - Inhibition of cisplatin-induced nephrotoxicity in rats by buthionine sulfoximine, a glutathione synthesis inhibitor. AB - DL-Buthionine-(S,R)-sulfoximine (BSO), a glutathione-depleting agent, was found to diminish the nephrotoxic effect of cisplatin (cis-diamminedichloroplatinum). Pretreatment of rats with BSO (4 mmol/kg s.c.) 2 h prior to cisplatin, either as a single dose of 5 mg/kg or at a daily dose of 2.5 mg/kg for 3 consecutive days, resulted in diminished elevations of plasma BUN concentration and decreased cisplatin-induced inhibition of renal gamma-glutamylcysteine synthetase and gamma glutamyl transpeptidase activity measured 6 days following treatment. Administration of BSO prior to cisplatin at 7.5 mg/kg did not significantly alter the effect of cisplatin on either BUN concentration or enzyme activity. The influence of BSO pretreatment on the antitumor activity of cisplatin was studied using implantation of a murine bladder cancer (MBT-2) in C3H mice. Pretreatment of mice with BSO (5 mmol/kg) did not influence cisplatin antitumor efficacy. PMID- 2890444 TI - Modulation of gamma-glutamyltranspeptidase in normal rat hepatocytes in culture by cell density, epidermal growth factor and agents which alter cell differentiation. AB - To help clarify whether elevation of gamma-glutamyltranspeptidase (GGT) in hepatocytes is associated with particular pattern(s) of liver differentiation, adult rat hepatocytes in primary culture were maintained for up to 5 days under conditions considered to alter differentiation in liver or other cells: basal GGT activity in untreated cultures and inducibility of the enzyme by known inducers such as dexamethasone, p,p'-dichlorodiphenyltrichloroethane or pregnenolone 16 alpha-carbonitrile were measured. Basal and induced GGT activities were maximal in confluent cultures and declined with decreasing cell density, an effect probably mediated by cell contact rather than factors in the culture medium. Opposite effects of cell density on GGT and DNA synthesis suggest that increased GGT activity is not linked with growth. Epidermal growth factor (EGF) increased basal GGT and augmented the action of xenobiotic inducers in lower density cultures, giving GGT activities approaching the levels in confluent cells. EGF had no effect on confluent cultures. Activators of protein kinase C such as tetradecanoyl phorbol acetate had significant but small inducing effects on GGT. Agents including all-trans retinoic acid, butyrate and dimethylsulfoxide which are considered to favour terminal differentiation in many cell types, all partly blocked induction of GGT by dexamethasone, EGF or xenobiotics. The results are consistent with (but do not prove) the view that elevated GGT activity may be associated with liver phenotype(s) distinct from terminal differentiation but not necessarily linked with growth. PMID- 2890445 TI - The preparative isolation of endosome fractions: a review. AB - The endosome is an intracellular, acidic, membrane-bound, subcellular compartment to which endocytosed ligands, receptors and plasma membrane proteins are conveyed before sorting and delivery to destinations elsewhere in the cell. The preparative isolation of elements of this compartment has been achieved successfully using various appropriate combinations of density gradient ultracentrifugation, electrophoretic, gel filtration and immunoaffinity techniques. These methods for isolating endosome fractions are reviewed together with the difficulties of establishing markers for such fractions. The isolation of an endosome fraction from the pathway of polymeric IgA transcytosis in rat liver is discussed to exemplify successful isolation procedures and appropriate subcellular markers. PMID- 2890446 TI - Endothelium-derived relaxing factor from pulmonary artery and vein possesses pharmacologic and chemical properties identical to those of nitric oxide radical. AB - The objective of this study was to elucidate the close similarity in properties between endothelium-derived relaxing factor (EDRF) and nitric oxide radical (NO). Whenever possible, a comparison was also made between arterial and venous EDRF. In vascular relaxation experiments, acetylcholine and bradykinin were used as endothelium-dependent relaxants of isolated rings of bovine intrapulmonary artery and vein, respectively, and NO was used to relax endothelium-denuded rings. Oxyhemoglobin produced virtually identical concentration-dependent inhibitory effects on both endothelium-dependent and NO-elicited relaxation. Oxyhemoglobin and oxymyoglobin lowered cyclic guanosine monophosphate (cGMP) levels, increased tone in unrubbed artery and vein, and abolished the marked accumulation of vascular cGMP caused both by endothelium-dependent relaxants and by NO. The marked inhibitory effects of oxyhemoglobin on arterial and venous relaxant responses and cGMP accumulation as well as its contractile effects were abolished or reversed by carbon monoxide. These observations indicate that EDRF and NO possess identical properties in their interactions with oxyhemoproteins. Both EDRF from artery and vein and NO activated purified soluble guanylate cyclase by heme-dependent mechanisms, thereby revealing an additional similarity in heme interactions. Spectrophotometric analysis disclosed that the characteristic shift in the Soret peak for hemoglobin produced by NO was also produced by an endothelium-derived factor released from washed aortic endothelial cells by acetylcholine or A23187. Pyrogallol, via the action of superoxide anion, markedly inhibited the spectral shifts, relaxant effects, and cGMP accumulating actions produced by both EDRF and NO. Superoxide dismutase enhanced the relaxant and cGMP accumulating effects of both EDRF and NO. Thus, EDRF and NO are inactivated by superoxide in a closely similar manner. We conclude, therefore, that EDRF from artery and vein is either NO or a chemically related radical species. PMID- 2890447 TI - Augmentation of renal blood flow and sodium excretion in hypertensive patients during blood pressure reduction by intravenous administration of the dopamine1 agonist fenoldopam. AB - Activation of dopamine1 (DA1) receptors relaxes vascular smooth muscle, especially in the renal vascular bed. Fenoldopam, the first selective DA1 receptor agonist that can be administered to man, was infused intravenously in 17 patients with essential hypertension (mean blood pressure 152/101 mm Hg). It reduced blood pressure in a dose-dependent fashion at doses between 0.025 and 0.5 microgram/kg/min and the antihypertensive effect was sustained during 2 hr infusions. In 10 patients studied during free-water diuresis, fenoldopam increased renal plasma flow by 42%, glomerular filtration rate by 6%, and sodium excretion by 202%, while lowering mean arterial pressure by 12% (all p less than .05). Similar promotion of sodium excretion was observed during blood pressure reduction in six additional patients studied without water loading. Pronounced enhancement of renal function in spite of blood pressure reduction suggests that fenoldopam might have a special role in the treatment of patients with hypertension and renal impairment. PMID- 2890448 TI - Hemodynamic and neurohumoral responses to dynamic exercise: normal subjects versus patients with heart disease. AB - Exercise testing has assumed a position of growing importance in the assessment of patients with chronic congestive heart failure. The hemodynamic and neurohumoral adjustments that occur during dynamic exercise are very complex, but are basically designed to ensure that oxygen delivery is commensurate with oxygen demand. These responses are clearly altered in the presence of certain types of heart disease. Patients with chronic congestive heart failure have an attenuated heart rate and blood pressure response throughout exercise, but this is most clearly evident when the data are expressed as a percent of peak oxygen consumption (VO2) rather than as a function of absolute VO2. Likewise, the sympathetic response to exercise is altered in patients with heart failure. Plasma norepinephrine is normally augmented as a function of VO2 during exercise, but this augmentation occurs during the later stages (beyond 50% of peak VO2). Patients with congestive heart failure show a greater than normal augmentation of plasma norepinephrine during exercise when the data are expressed in terms of absolute VO2. However, when the data are expressed as a percent of peak VO2, there appears to be a relative attenuation of the sympathetic response to exercise. Current information suggests that increased plasma norepinephrine and renin activity during exercise in patients with heart failure are not directly related to a decrement in nutritive blood flow to skeletal muscles. The mechanisms responsible for exercise intolerance in patients with heart failure are not known, but do not seem directly related to a decrement in cardiac output or an increase in left ventricular filling pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890449 TI - Production and certification of an enzyme reference material for gamma glutamyltransferase (CRM 319). Part 1: Preparation and characterization. AB - We have produced a batch of lyophilized gamma-glutamyltransferase as enzyme reference material. The "light" enzyme form was purified from pig kidney to a relatively high specific activity (120 kU/g) and was essentially free of contaminating enzymes. The partly purified gamma-glutamyltransferase, lyophilized in a matrix containing bovine serum albumin (Fraction V, 60 g/L), yielded a batch of 4000 ampules and was stored at -20 degrees C. The vial-to-vial variability with respect to the catalytic concentration of the final product (CV 0.6%) and its stability (predicted loss of activity at -20 degrees C was less than 0.01% per year) were considered sufficient to allow the use of this preparation for a certification procedure. The behavior of the reference material in comparison with human serum samples was evaluated three ways: (a) by kinetic characteristics, (b) by the ratio of activities for duplicate determinations by different methods, and (c) by use of the reference material to convert values obtained by various methodologies to those by the IFCC proposed method. The material appeared to be commutable for the two methods studied. The difference in the ratios obtained for patients' samples and reference material was less than +/ 5%, and the recalculated values for patients' samples as determined with the reference material differed from values determined by the IFCC method by no more than 4.8%. PMID- 2890450 TI - Production and certification of an enzyme reference material for gamma glutamyltransferase (CRM 319). Part 2: Certification campaign. AB - We describe the process of certification for a gamma-glutamyltransferase reference material (CRM no. 319). Fifteen laboratories participated to this interlaboratory evaluation. All steps of the measurements were controlled in an effort to locate potential sources of variations. In particular, the exclusion of some data was strictly documented or justified by the non-observance of the IFCC method and (or) discrepancies in instrumentation, reconstitution of the lyophilized samples, or measurement technique. Inaccuracy in the reconstitution of the lyophilized material was +/- 0.68%, and the molar absorptivity of the 5 amino-2-nitrobenzoate reported by each laboratory was within +/- 2% limits of the value reported by the IFCC. Calculated from the sets of accepted results, the total CV among samples was 2.6% and the overall CV was 3.2%. Within-day and between-day CVs were 1.1% and 1.4%, respectively. The greatest variation for a single component was the between-laboratory variability (CV 3.1%); the within laboratory CV, including the day effect, was 1.8%. Finally, the certified value for the catalytic concentration of this enzyme in the reconstituted lyophilized reference material was 86.8 U/L with an uncertainty of +/- 2.1 U/L (0.95 confidence interval). The uncertainty appeared to be compatible with the end-use of this reference material. PMID- 2890451 TI - Diagnostic significance of different urinary enzymes in patients suffering from chronic renal diseases. AB - The urinary enzymes alanine aminopeptidase (EC 3.4.11.2), alkaline phosphatase (EC 3.1.3.1), gamma-glutamyltransferase (EC 2.3.2.2), N-acetyl-beta-D glucosaminidase (EC 3.2.1.30), and ribonuclease (EC 3.1.4.22) were measured in 66 healthy persons and 52 patients suffering from chronic renal diseases (pyelonephritis, glomerulonephritis). The residual renal function of patients characterized by 99mTc-diethylenetriaminopentaacetate isotope clearance was only moderately reduced. Except for gamma-glutamyltransferase, patients generally showed increased urinary enzyme excretions. N-Acetyl-beta-D-glucosaminidase was more sensitive to detect renal dysfunction than the other enzymes and the conventional parameters serum creatinine, total protein excretion, and the measurement of glomerular filtration rate. The determination of this enzyme can be recommended as a suitable diagnostic parameter in nephrology. PMID- 2890452 TI - The absence of gamma-glutamyltransferase in erythrocyte membranes. PMID- 2890453 TI - Efferent renal nerve activity in hypertensive man. AB - In a series of investigations we have evaluated efferent renal nerve activity in hypertensive man. Net renal release of noradrenaline, calculated as the arterio venous gradient for noradrenaline across the kidney times flow, was taken as an index of local adrenergic activity. Renal blood flow, under various circumstances, was determined by xenon-washout. At rest noradrenaline release was variable but enhanced release, indicative of increased sympathetic activity, invariably was found during isometric exercise. The latter was associated with renal vasoconstriction. Further studies, employing intrarenal infusions of either the alpha-1 antagonist doxazosin or the alpha-2 antagonist yohimbine in doses that do not produce systemic effects, demonstrate that adrenergic vasoconstriction both at rest and during isometric exercise is accomplished mainly through alpha-2 receptors. It may be that an alpha- adrenoceptor mediated vascular response also determines the efficacy of chronic beta-blockade. PMID- 2890454 TI - The enteric nervous system in the control of motility and secretion. PMID- 2890455 TI - Introduction of genomic diagnosis of classical phenylketonuria to the health care system of the German Democratic Republic. AB - The phenylketonuria (PKU) dispensary of the Children's Hospital of the Charite, Berlin, GDR, cares for about 140 affected families, representing about one-third of all PKU families in the GDR. Of these families, 15 expressed their desire for an additional child given the availability of a reasonably reliable prenatal diagnosis procedure. They were investigated by linked RFLP analysis applying a phenylalanine-hydroxylase-cDNA probe. Full genetic predictability for prospective fetuses could be obtained for all of them. In eight cases this was possible by the use of one restriction enzyme, and in the remaining seven by a combination of the information from two restriction-enzyme patterns. No recombination between linked RFLP and the PKU phenotype could be observed in 40 meioses from the investigation of eight families with two affected children each. PMID- 2890456 TI - Prenatal diagnosis of glycerol-kinase deficiency associated with a DNA deletion on the short arm of the X-chromosome. AB - Amniocentesis was performed in a woman who previously had given birth to a boy who died at 12 months of age with a diagnosis of glyceroluria and adrenal insufficiency. A high amount of glycerol (9.0 standard deviations above mean for controls) was found in the amniotic fluid. Enzyme activity of glycerol-kinase (ATP:glycerol-3-phosphotransferase, EC 2.7.1.30) in the cultured amniotic fluid cells was very low. The pregnancy was terminated and a male fetus was aborted. Examinations of DNA isolated from the fetus did demonstrate deletions of two out of 16 DNA probes mapping to the short arm of the X-chromosome. The probes failing to hybridize to DNA from the fetus were C7 (DXS28) and L1.4 (DXS68), both mapping to Xp21.3 and located terminal to the Duchenne locus. PMID- 2890457 TI - Nature of the gastric acid-gastrin feedback loop in the fetal sheep. AB - 1. The neonates of sheep and other species have a decreased gastric acid secretion but an elevated plasma gastrin concentration. 2. Since low gastric acid secretion is a stimulus for gastrin release in mature animals the present study examined whether the relative hypochlorhydria in the sheep fetus was sustaining the hypergastrinaemia. 3. Fetal plasma gastrin was measured following fetal gastric acidification (pentagastrin infusion) and gastric neutralization (parietal cell blockade with the proton pump inhibitor omeprazole) in chronically cannulated fetal sheep from 101 days until term (145 days). 4. Acutely raising gastric pH with omeprazole increased plasma gastrin in the mature sheep. However, in the fetus increasing the pH with omeprazole or decreasing pH with pentagastrin had no effect on fetal plasma gastrin. This was true for fetuses from all age groups. 5. The results indicate that the gastric acid-gastrin feedback loop is not functional in the fetus and that the hypergastrinaemia at birth is therefore not the result of the relative hypochlorhydria. 6. The time after birth when the gastric acid-gastrin feedback loop matures remains to be determined. PMID- 2890458 TI - The relationship between neuroleptic dosage and cognitive functioning in chronic schizophrenic patients. AB - A review of the effects of phenothiazines on cognitive function suggests that phenothiazine derivatives facilitate performance on tests of cognitive function, at least in subjects who are thought disordered. Drug effects frequently depend on the dose administered, however, and the response to various doses of some drugs (e.g., antidepressants) is frequently nonlinear. In our study, 23 hospitalized males with chronic psychotic disorders, and stabilized on dosages of neuroleptics with chlorpromazine equivalents of from 50 to 7,200 milligrams daily, were tested in the morning and in the evening of the same day with the Mini-Mental State examination [1]. Cognitive functioning was positively correlated (+0.49) with dosage, but the relationship was curvilinear. Functioning improved with increasing dose up to a dose of about 2,000 milligrams daily; beyond that dosage (and up to 7,200 milligrams daily) functioning plateaued. Scores on same-day retest were essentially unchanged regardless of dose. The implication of these findings for the management of chronic psychotic patients is discussed. PMID- 2890460 TI - H2-receptor blocking agents and hepatic drug elimination. PMID- 2890459 TI - Absorption studies of the H2-blocker nizatidine. AB - The absolute and relative bioavailability of nizatidine, an H2-blocker, was studied in healthy male volunteers. The absolute oral bioavailability, relative to that after intravenous administration, was 98% +/- 14%. The bioavailability of single and multiple oral doses of 150 mg nizatidine was unaffected by concurrent food ingestion; nizatidine may be administered either with or without food. The relative bioavailability of nizatidine was compared when given simultaneously with placebo or Gelusil, 30 minutes after propantheline, or 60 minutes before activated charcoal. Gelusil reduced the amount of nizatidine absorbed by about 10%, charcoal reduced it by about 30%, and propantheline did not affect it. PMID- 2890461 TI - Effectiveness of 15-mL versus 30-mL doses of syrup of ipecac in children. AB - The rates at which 15- and 30-mL doses of syrup of ipecac induced emesis within 30 minutes were evaluated in pediatric patients treated for accidental poisoning. A two-year prospective study was conducted to collect data on 4306 pediatric patients (aged one to six years) who received syrup of ipecac to treat accidental poisoning. Patients received either 15-mL (during 1983) or 30-mL (during 1984) doses of syrup of ipecac and 120-240 mL of water or clear liquid. Time of administration and time of the first episode of emesis were reported by the person administering the syrup of ipecac; the difference between these times was recorded as the time to emesis. Successful emesis was defined as emesis within 30 minutes after ipecac administration, while failure was defined as emesis occurring more than 30 minutes after administration. Success and failure rates were compared using chi-square analysis. Syrup of ipecac 15 mL was administered to 1905 patients, resulting in a failure-to-produce-emesis rate of 8.82% (168 patients). Syrup of ipecac 30 mL was administered to 2401 patients, resulting in a 0.08% failure rate (two patients). A repeat dose of ipecac syrup in the 15-mL group yielded a 99.74% success rate, which was not significantly different from the 99.96% success rate after a single dose of 30 mL. Although syrup of ipecac dosing in pediatric patients is controversial, our data suggest that increasing the standard pediatric dose from 15 to 30 mL significantly reduces the emesis failure rate. PMID- 2890462 TI - Beta-adrenergic blocking drugs in the management of hypertension. PMID- 2890463 TI - Blood flow uphill and downhill: does a siphon facilitate circulation above the heart? AB - 1. Despite the continuity of the circulatory system, blood flowing down the veins of the neck does not assist blood flowing up the arteries. Because of collapsible veins, gravitational pressure gradients are not matched in arterial and venous sides of circulatory loops above the heart as would be necessary for a siphon to operate. 2. All animals have arterial blood pressures capable of lifting the blood to the head without the assistance from a siphon. In cases of longer vertical distances, such as in giraffes and climbing snakes, the heart does more work against the effects of gravity on the arterial blood column. 3. The potential energy of the blood in the head is lost as frictional heat produced in the veins. PMID- 2890465 TI - Urine analysis of European moles Talpa europaea and white rats Rattus norvegicus kept on a carnivore's diet. AB - 1. The urine compositions of the European mole Talpa europaea and of the white rat Rattus norvegicus (albino) kept on a carnivore's diet were compared. 2. The urine of moles contained bicarbonate while that of rats kept on a carnivore's diet did not. 3. Urine volume per 100 g body mass over 24 hr was significantly higher in the mole than in the rat. 4. The results of this study suggest that the mole, like other subterranean mammals on the one hand and caecal fermenters on the other, may use its kidneys as a pathway for releasing bicarbonate in its hypercapnic environment. PMID- 2890464 TI - The fruit bat as an experimental model of the neuropathy of cobalamin deficiency. AB - The fruit bat provides a unique small mammal model of the neurological changes associated with cobalamin deficiency. Work with this model has shown that methionine moderates the development of the neurological impairment. This action does not appear to be via the methyl donor S-adenosylmethionine, but its role in the provision of formate is not excluded. Furthermore, methylation reactions in the nervous system are not impaired in severe cobalamin deficiency, despite low levels of methionine synthetase activity. The accumulation of physiologically inactive analogues of cobalamin also do not appear to be aetiologically important in the neuropathy. Brain folates are minimally affected by severe cobalamin deficiency, although liver folates decrease significantly. Deranged GABA function in the brain may play a role in the symptomatology of cobalamin deficiency. There is some evidence for the hypothesis that deranged fatty acid metabolism in neural tissue contributes to altered membrane structure and hence function. Changes in the properties of membrane proteins may play a contributory role. The biochemical basis of the neuropathy has still to be fully elucidated. PMID- 2890466 TI - The physiology of infection with nematodes: the role of intracellular pH in the development of the early parasitic stage. AB - 1. H2CO3, the host's signal which induced (less than 25 min) the Ca2+-dependent development of the first parasitic stage of Haemonchus contortus, produced a diphasic change in the pHi (less than 30 min), measured with 5,5-dimethyl-2,4 oxazolidinedione, in the infective stage. The intensity of the diphasic change was related to the [H2CO3] and so to the efficiency of the stimulus for development. 2. MES and HEPES buffers induced a rapid rise in pHi of infective stages in step with pHo. Ortho-and pyrophosphate induced greater changes in pHi. Such buffers did not initiate development. 3. These and other results suggest that the stimulus for development, H2CO3, induced an energy-dependent Ca2+/H+ exchange mediated by mitochondria of the infective stage, which initiated development of the parasitic stage. PMID- 2890467 TI - Peripheral nerve conduction in the fruit bat with nitrous oxide induced vitamin b12 deficiency. AB - Fruit bats Rousettus aegyptiacus were depleted of vitamin B12 by exposure to the gas nitrous oxide (N2O-oxygen, 1:1 v/v) for 57-80 days. Conduction velocities along the fastest fibres of the ulnar nerve, as well as the first and second peaks, were similar in control and vitamin b12 depleted animals. It is concluded that neurological impairment resulting from depletion of vitamin B12 by N2O does not involve significant impairment of ulnar nerve function in this species. PMID- 2890468 TI - Comparative studies of elemental composition on ejaculated fowl, bull, rat, dog and boar spermatozoa by electron probe X-ray microanalysis. AB - 1. Comparative analyses of the concentrations of bulk and trace elements on the head, midpiece and tail regions of the ejaculated fowl, bull, rat, dog and boar spermatozoa were performed using X-ray microanalysis with scanning electron microscopy. 2. Although the pattern of distribution of elements on the surface of the three different subcellular regions was, in general, similar among all the species, there were substantial shifts in absolute concentrations. 3. Concentration of magnesium on the dog spermatozoa was significantly higher (about 2 times) than those of the other species. 4. Zinc, copper, iron and manganese concentrations were higher on fowl spermatozoa compared with those of the other species studied. 5. The Na-to-K ratios on the midpiece ranged from 1.46 (rat) to 2.26 (dog). PMID- 2890469 TI - The enterohepatic recycling of bile choline in sheep. AB - 1. Measurement of unesterified choline in blood samples taken from five conscious multi-cannulated sheep indicated a significant production of unesterified choline by the alimentary tract, as judged by the portal venous minus arterial difference and significant uptake by the liver, as judged from the portal venous minus hepatic venous and arterial minus hepatic venous differences. 2. A mean liver blood flow rate of 1.68 +/- 0.22 1/min for the five sheep was determined by bromosulphophthalein clearance and, combined with the differences in unesterified choline across organs, gave a production rate of free choline of 9.1 mmol/day by the alimentary tract and an uptake by the liver of 13.2 mmol/day. 3. Infusion of [methyl-3H]choline chloride into the portal vein of a sheep over 1 hr and subsequent isolation of the bile for several days showed over 70% cumulative recovery of the radioactivity in the choline moiety of bile phosphatidylcholine over a 120 hr period. 4. Subsequent infusion 17 days later of bile lipid [3H]choline via a duodenal fistula also gave approx. 70% cumulative recovery of radioactivity in the choline moiety of newly secreted bile phosphatidylcholine in 120 hr. 5. These results show a very extensive enterohepatic recirculation of bile choline in the sheep, which is in contrast to the situation in monogastric animals. PMID- 2890470 TI - Fluid secretion rates from mouse and rat parotid glands are markedly different following pilocarpine stimulation. AB - 1. Parotid saliva production in two commonly employed laboratory animals, mouse and rat, was studied following pilocarpine stimulation. 2. When normalized to body wt, average parotid saliva output rates in mice were 3-4-fold greater than those observed in rats. When parotid salivary flow rates were normalized to gland weight, mice still displayed 2-3-fold higher values than rats. 3. The Na+ and K+ content of parotid saliva showed small differences between the two species, while saliva from rats contained 3-fold higher protein levels than observed with mice. PMID- 2890471 TI - Glucose uptake after immobilization in fast and slow skeletal muscle in rats. AB - 1. 3-O-methylglucose uptake was studied after immobilization in rat extensor digitorum longus (EDL) and soleus (Sol) muscles. 2. The immobilization of the ankle was done in one of extreme positions by plaster casts. 3. In both positions, 3-O-methylglucose uptake in EDL increased and that in Sol decreased after immobilization. 4. When immobilization was released uptake returned to control level. 5. The change in uptake after immobilization and after release of immobilization was earlier in Sol. PMID- 2890472 TI - Parathyroid hormone stimulation of renal adenylate cyclase in various vertebrate species: evidence for an effect in the frog. AB - The effect of [Nle8,18,Tyr34]bPTH-(1-34)amide on renal plasma membrane adenylate cyclase, in the presence of 0.1 mM guanylylimidodiphosphate was measured in rat, chicken, frog and trout. All species showed an enrichment of at least 8-fold (relative to homogenate) in the marker enzyme Na+,K+-ATPase. A significant dose dependent adenylate cyclase stimulation was found in frog, with affinity values similar to those of rat and chicken (ED50=8, 10 and 3 nM, respectively), but not in trout. The frog response was specific since [Nle8,18,Tyr34]bPTH-(3-34)amide strongly inhibited the agonist-stimulated enzyme. These results suggest the existence of a PTH-like substance in anurans acting via cyclic AMP formation in the kidney. PMID- 2890473 TI - Inhibitory effect of the extract from Zizyphus jujuba leaves on sweet taste responses of the chorda tympani in the rat and hamster. AB - 1. One of the fractions obtained from the extract of Zizyphus jujuba leaves suppressed the response of the chorda tympani to sucrose, both in the rat and hamster. 2. In the rat and man, suppressive effect was found to be significant in responses to various sugars and artificial sweeteners but not in some sweet amino acids. PMID- 2890474 TI - Scaling of maximal lifespan in bats. AB - 1. Values for maximal lifespan in heterothermic and homeothermic bats as a function of body weight, brain weight and lifetime basal energy consumption were submitted to linear (log-log) and multiple regression analysis. 2. The results of the regression analyses of maximal lifespan in bats were compared with those reported for non-flying mammals based on both narrow and wide weight ranges. 3. It was found that the regression lines (linear or multiple) for maximal lifespan in bats (heterothermic or homeothermic) lie well above the regression lines for non-flying mammals. 4. Predictions of maximal lifespan in heterothermic bats based on estimated lifetime basal energy consumption and body weight are in reasonable agreement with observed values when torpor and hibernation behaviour are taken into account. 5. But observed values of maximal lifespan in homeothermic bats were found to lie substantially above the regression lines derived for non-flying mammals. 6. It was concluded that existing hypotheses do not account for the long lifespan observed in bats generally. PMID- 2890475 TI - An analysis of the adenosine receptors responsible for modulation of an excitatory acetylcholine response on an identified Helix neuron. AB - 1. Electrophysiological recordings were made from an identified neuron, F1, in the isolated suboesophageal ganglionic mass of Helix aspersa. 2. Bath applied adenosine (AD) (60-600 nM) depressed the depolarisation induced in the cell F1 by bath or iontophoretically applied acetylcholine (ACh). L-Phenylisopropyladenosine (L-PIA) also depressed the ACh response but NECA had no depressive effect. This effect of AD or L-PIA is inhibited by 12 microM 8-phenyltheophylline and is believed to be mediated by an A1 receptor. 3. If the proportion of the excitatory ACh response that was carried by calcium ions was increased, the percentage depression of this modified response by AD was significantly greater. 4. There was a residual current evoked by ACh in high calcium/sodium free Ringer. This ACh induced current was antagonized by 3 mM cobalt or 50 microM verapamil suggesting that it was calcium mediated. This residual current was also completely abolished by 0.6 microM AD. 5. Lower bath concentrations of AD (0.6-6 nM) and L-PIA than caused the depression of the ACh response and also adenosine triphosphate (ATP) (0.7 microM) and alpha,beta-methylene ATP (0.6 microM), enhanced the ACh D response. The relative potencies of AD and its two analogues 5'-N ethylcarboxamideadenosine (NECA) and L-PIA in causing this enhancement of the ACh response were: NECA greater than AD greater than L-PIA. This is the potency ranking described for an A2 receptor. PMID- 2890476 TI - Xenobiotic biotransformation in livers and lungs of adult black-tailed deer: comparison with domestic goat and sheep. AB - 1. The capacity of liver and lung tissue of black-tailed dear (Odocoileus hemionus columbianus) to biotransform xenobiotics was compared in vitro to the domestic sheep and goat. Donor animals were all females of varying ages. Tissues from the black-tailed deer were collected in the wild. A variety of biotransformation enzymes were measured in both microsomal and cytosolic fractions. 2. Deer liver was lower in total cytochrome P450 concentration, but mono-oxygenase activities were greater compared to sheep and goat. The opposite was true for the lung. 3. Epoxide hydrolase activities were significantly different in deer vs sheep and goat. 4. In general, both hepatic and pulmonary activities were more similar between sheep and goat than either species compared to the deer, however, the magnitude of the hepatic differences did not exceed 5 fold. 5. Based on these limited results, there is no reason to discredit the sheep or goat as a toxicity testing model for deer. PMID- 2890477 TI - Mixed-function oxidase activity in seabirds and its relationship to oil pollution. AB - 1. The hepatic activity of epoxide hydrolase, aldrin epoxidase, aminopyrine N demethylase, 7-ethoxyresorufin O-deethylase, benzo(a)pyrene 3-hydroxylase and UDP glucuronyl transferase was determined in adult herring gulls (Larus argentatus) at various stages of the breeding season. 2. MFO activity was measured for adult Leach's storm-petrels (Oceanodroma leucorhoa), guillemot (Uria aalge) and Atlantic puffins (Fratercula arctica). For most assays the values were highest for the puffin. 3. MFO activity in both nestling and adult Atlantic puffins was determined. The degree of induction caused by a single internal dose of Prudhoe Bay crude oil in adult puffins and that caused by multiple internal doses in nestling puffins was measured. PMID- 2890478 TI - GABA binding in bovine adrenal medulla membranes is sensitive to baclofen. AB - 1. The data summarized in this report reveals the existence of GABA binding in the bovine adrenal medulla membranes. 2. Since this binding was displaced not only by muscimol and bicuculline but also by baclofen, results suggest the possibility that both types of receptors (GABAA and GABAB) could be present in bovine adrenal membranes. PMID- 2890479 TI - Hepatic biotransformation in lean and obese Wistar Kyoto rats: comparison to that in streptozotocin-pretreated Sprague-Dawley rats. AB - 1. Phase I and phase II biotransformation was compared in streptozotocin-induced hypoinsulinemic (STZ) and genetic hyperinsulinemic (WKY-fatty) rats. 2. Total cytochrome P-450 concentrations were reduced in both STZ and WKY, whereas styrene oxide hydrolase and benzphetamine N-demethylase activities were normal in STZ and reduced in WKY. 3. UDP-glucuronosyltransferase activity was decreased toward testosterone and 1-naphthol in STZ and WKY, and was increased toward estrone in the obese female WKY. 4. Glutathione S-transferase activity was decreased in STZ toward 1-chloro-2,4-dinitrobenzene, ethacrynic acid and sulfobromophthalein, but was similar to that in normal rats for WKY. PMID- 2890481 TI - Metabolic activation of 2-aminofluorene, 2-acetylaminofluorene and N-hydroxy acetylaminofluorene to bacterial mutagens with mussel (Mytilus galloprovincialis) and carp (Cyprinus carpio) subcellular preparations. AB - 1. The mode of activation of 2-aminofluorene (AF), 2-acetylaminofluorene (AAF) and N-hydroxy-acetylaminofluorene (OH-AAF) to Salmonella typhimurium TA 98 mutagens was investigated in subcellular fractions from the digestive gland of the mussel Mytilus galloprovincialis and from the liver of carp Cyprinus carpio. 2. In carp liver microsomes the activation of OH-AAF was due to very active deacetylase, in contrast to undetectable deacetylase-dependent activation in mussel microsomes. 3. AF and AAF are activated in mussel microsomes exclusively by a noninducible FAD-containing monooxygenase, whereas in carp microsomes in addition deacetylase and inducible cytochrome P-450 monooxygenase are involved. 4. N,O-Acetyltransferase, sulfotransferase and paraoxon sensitive cytosolic enzyme (PSCE) are involved in activation of OH-AAF, AF and AAF in both carp and mussel cytosols. 5. The metabolic activation of OH-AAF, AF and AAF to bacterial mutagens found in carp liver is similar to that described in livers of experimental mammalian species and strikingly different from the mode of activation found in mussel digestive gland. PMID- 2890480 TI - Difference in calcium sensitivities of the sodium transporting systems in the nervous system of susceptible and kdr-resistant houseflies, Musca domestica L. AB - 1. The synaptosomal preparations from the kdr-resistant strains have lower responsiveness to externally applied Ca2+ than the susceptible counterparts with respect to their Na+/Ca2+ exchange, Na+ uptake, Na+-Ca2+ protein kinase phosphatase and its phosphorylation activities. 2. In vivo toxicity tests support the above in vitro observation in that the kdr-resistant strain shows a significant cross-resistance to agents known to affect the Na+ channel operations, those which increase intracellular Ca2+ or act as effective Ca2+ substitutes. 3. Such evidence indicates a possibility of a causal relationship between kdr resistance and the reduction of Ca2+ sensitivity by these ATP utilizing systems including the Na+ transporting systems in the resistant insects. PMID- 2890482 TI - Inhibition of growth and respiration of Leishmania mexicana by the antitumor agent lonidamine. AB - 1. The antitumor drug lonidamine inhibited growth of promastigotes of Leishmania mexicana in axenic culture. 2. Fifty percent inhibition was attained at 0.42 mM, and was reflected mainly in an increase in lag time, with less effect on final cell yield. 3. The drug was leishmanistatic, since when a non-growing culture in the presence of 0.5 mM lonidamine was centrifuged and the cells resuspended in fresh medium, growth started and reached the control value. 4. Both coupled and FCCP-uncoupled respiration of intact promastigotes were inhibited by lonidamine; 50% inhibition was attained at 0.5 and 0.4 mM, respectively. 5. The results suggested that the mechanism of inhibition of growth of L. mexicana is, as proposed in the case of Trypanosoma cruzi epimastigotes and Trypanosoma brucei procyclic trypomastigotes, through inhibition of the energy metabolism. PMID- 2890483 TI - Inhibition of Na+-Ca2+ exchange mechanism in cardiac sarcolemmal vesicles by harmaline. AB - 1. Harmaline was found to inhibit the Na+-Ca2+ exchange mechanism present in cardiac sarcolemmal vesicles. 2. The inhibition was dose-dependent and was observed in the range 10(-5) M-10(-2) M harmaline. 3. The effect was demonstrated on both 45Ca2+-uptake and 45Ca2+-efflux. 4. The observed Ki value for harmaline inhibition of 45Ca2+-uptake was found to be 2.5 X 10(-4) M. PMID- 2890484 TI - Chemical denervation of the myenteric plexus of the muscular stomach of turkeys. AB - 1. The thin caudoventral muscle (TCM) of the muscular stomach of domestic turkeys was surgically exposed and painted with solutions of saline or 0.1, 0.25, 0.5, and 1.0% benzalkonium chloride (BC), a cationic surfactant shown to irreversibly damage neurons but not muscle tissue in mammals. 2. Following fluoroscopic observations of gastric motility for 2 weeks, turkeys were euthanized, the entire muscular stomach was excised and weighed, and serial frozen sections of the TCM were taken for evaluation of the number and size of neurons in the myenteric plexus. 3. Treatment with 0.5 and 1.0% BC resulted in loss of motility in the TCM, significant hypertrophy (P less than 0.001) of the CTM, a 70% decrease in number and 60% decrease in size of myenteric neurons, and a 4-fold increase in thickness of the serosa, compared with saline-treated controls. PMID- 2890485 TI - A comparison of dressed crab and a cadmium salt (CdCl2) as cadmium sources in rat diets. AB - 1. A long term low level exposure experiment was conducted on rats in order to determine the metabolic patterns of realistic environmental dietary levels of cadmium from different sources. 2. Male and female rats were fed a diet for 6 months with a high crab content containing 4 mg Cd/kg as organic bound cadmium from dressed crab, a diet with low crab content containing 0.2 mg Cd/kg as organic bound cadmium, a casein based diet containing 4 mg Cd/kg as cadmium chloride and a low cadmium level control diet. 3. Analysis of the cadmium levels in the kidney, liver and spleen showed that uptake from the dressed crab was only half of that from the diet fortified with cadmium chloride. PMID- 2890486 TI - Binding of [14C] DDT by submitochondrial particles. AB - 1. Binding of [14C] DDT by submitochondrial particles and by liposomes prepared from lipids extracted from the particles was studied by the discontinuous sucrose gradient method. 2. Binding of the insecticide was a biphasic linear function of the biomembrane- and liposome-concentration with a break in the binding curve occurring at identical concentrations of phospholipid for both the biomembrane and vesicle. The biphasic binding curve is interpreted in terms of decreased availability of binding sites as a result of particle-particle interaction. 3. [14C] DDT was bound mainly by the membrane lipids and only negligible binding was detected for the delipidated membrane. 4. A 100-200-fold excess of unlabeled DDT had no effect on the binding of [14C] DDT and a 600-fold excess of unlabeled DDT reduced the binding by 20% suggesting that binding of [14C] DDT by lipids was nonspecific. 5. These results are discussed in relation to the strong inhibition by DDT of mitochondrial bioenergetics. PMID- 2890487 TI - Lead effects in the chick during selenium deficiency. AB - 1. Growing chicks (Gallus domesticus) were fed a selenium-deficient diet supplemented with 0 or 2000 ppm lead (Pb) and 0 or 0.1 ppm selenium (Se). 2. Selenium addition stimulated growth at 0 but not at 2000 ppm Pb, while Pb depressed growth at both levels of Se. 3. Selenium addition stimulated Se dependent glutathione peroxidase (GSH-Px) activity in liver, but Pb was without effect on GSH-Px activity. 4. Lead addition increased non-protein sulfhydryl (NPSH) concentrations in liver, kidney and thigh muscle. NPSH levels were not altered by Se. 5. The reported antagonism between Pb and Se does not appear to be mediated through effects on GSH-Px or NPSH metabolism. PMID- 2890488 TI - The mouse neocortical slice: preparation and responses to excitatory amino acids. AB - 1. An improved method of preparing wedges of cerebral cortex and corpus callosum from 500 microM thick coronal sections using mouse brain is described. 2. The characteristics of mixing in the two compartment baths is fully reported. 3. Cortical tissue could be depolarized relative to callosal tissue by superfusion of N-methyl-D-aspartate (NMDA), quinolinate, kainate or quisqualate. 4. At higher concentrations of agonists the depolarization was followed by a small hyperpolarization. This hyperpolarization was abolished by 5 microM ouabain. 5. Neither TTX (1 microM) nor bicuculline (50-62.5 microM) significantly affected the amplitude of the responses to the excitatory amino acids. 6. Responses to NMDA and quinolinate were selectively reduced by magnesium ions, 2-amino-5 phosphonovalerate or ketamine. PMID- 2890489 TI - Osmoregulatory actions of angiotensin II are independent of adrenergic receptor mechanisms in the duck, Anas platyrhynchos. AB - 1. Intravenous infusion of a physiological dose of fowl angiotensin II (ANG II) in salt-loaded ducks raised systemic arterial blood pressure, inhibited nasal salt gland fluid and solute secretion, and stimulated renal-cloacal urine production. 2. Beta-adrenergic receptor blockade by propranolol lowered arterial pressure but did not prevent the effects of ANG II on salt and water excretion. 3. Alpha-adrenergic receptor blockade by prazosin decreased both arterial pressure and plasma glucose levels, but it did not impair the osmoregulatory actions of ANG II. 4. These observations indicate that redistribution by ANG II of salt and water excretion is independent of adrenergic receptor mechanisms and therefore does not depend on the sympathomimetic activity of the hormone. PMID- 2890490 TI - Responses of the melanophores of the medaka, Oryzias latipes, to adrenergic drugs: evidence for involvement of alpha 2 adrenergic receptors mediating melanin aggregation. AB - 1. Melanin-aggregation response of the medaka melanophores to a series of adrenergic drugs were examined. 2. Concentration-response curves for the drugs indicated that the melanin-aggregating effects of alpha 2 adrenergic agonists, naphazoline, tramazoline and clonidine, were more than 100-fold greater than that of alpha 1 agonists, phenylpropanolamine, phenylephrine, oxymetazoline and methoxamine. 3. The inhibitory effect of alpha 2 antagonist, yohimbine, on the cell responses to the agonists were also about 100-fold greater than that of alpha 1 antagonists, corynanthine and prazosin. 4. These results indicate that adrenergic receptors which mediate melanin-aggregation response of the cells are alpha 2 in nature. PMID- 2890491 TI - A subtype of adenosine receptors mediating pigment dispersion in leucophores of the medaka: evidence for an A2-receptor. AB - 1. Adenosine and its derivatives induced dispersion of leucosomes in leucophores of the medaka, Oryzias latipes. 2. Among the purines used, 5'-N ethylcarboxiamideadenosine was the most effective and its potency was far greater than that of adenosine, N6-L-phenylisopropyladenosine and N6-cyclohexyladenosine. 3. Methylxanthines inhibited the purine action competitively, but beta adrenergic antagonists and dipyridamole did not. 4. Beta adrenergic agonists and forskolin synergistically augmented the purine action, while Li+ blocked it competitively. 5. The results suggest that medaka leucophores possess A2 adenosine receptors on the cell membranes, the stimulation of which induces leucosome-dispersion response by increasing the cellular level of cyclic AMP through activation of adenylate cyclase activity. PMID- 2890492 TI - Characterization of some monooxygenase activities and solubilization of hepatic cytochrome P-450 in two species of freshwater fish, the nase (Chondrostoma nasus) and the roach (Rutilus rutilus). AB - 1. Hepatic monooxygenase activities were studied in microsomal fractions from two species of freshwater fish, the nase (Chondrostoma nasus) and the European roach (Rutilus rutilus). 2. These activities were determined by using four substrates, 7-ethoxycoumarin, 7-ethoxyresorufin, benzo(a)pyrene, and 2,5-diphenyloxazole and were characterized according to pH, temperature, cofactors, and the differential effects of two inhibitors, metyrapone and alpha-naphthoflavone. 3. Solubilization of microsomes was achieved by the use of detergents, with a good recovery of the cytochrome P-450. PMID- 2890493 TI - Comparison of basal glutathione S-transferase activities and of the influence of phenobarbital, butylated hydroxy-anisole or 5,5'-diphenylhydantoin on enzyme activity in male rodents. AB - 1. Hepatic cytosolic glutathione S-transferase (GST) activities, toward five substrates, were shown to vary markedly among three laboratory rodent species. 2. Basal GST activities for 1-chloro-2,4-dinitrobenzene (hamster greater than mouse greater than rat), 1,2-dichloro-4-nitrobenzene (mouse greater than rat greater than hamster), p-nitrobenzyl chloride (rat = mouse = hamster), bromosulfophthalein (rat greater than mouse greater than hamster) and 1,2-epoxy-3 (p-nitrophenoxy)propane (mouse greater than rat = hamster) differed with respect to magnitude and distribution among species. 3. GST substrate activities in response to phenobarbital, butylated hydroxy-anisole or 5,5'-diphenylhydantoin treatment were increased more often in mouse and rat as compared to the hamster. 4. These results suggest that basal GST activity, as well as inducibility, differ among rodent species. Since GST are involved in detoxication processes, differences in GST properties may underlie variability in species sensitivity to toxicants. PMID- 2890494 TI - The saliva of the medicinal leech Hirudo medicinalis--II. Inhibition of platelet aggregation and of leukocyte activity and examination of reputed anaesthetic effects. AB - 1. Leech saliva inhibits platelet aggregation induced by collagen, ADP and epinephrine. 2. Leech saliva inhibits superoxide production by neutrophils stimulated by tetradecanoyl phorbol acetate or polyhistidine. The effect is due in part at least to eglin. 3. Reputed anaesthetic effects of leech saliva were not detected. PMID- 2890495 TI - Evidence that herbicides relaxing smooth and oblique-striated muscles affect the muscle cell membrane. AB - 1. From the example of two herbicides [chlorpropham (CIPC) and terbutryn], it has been shown that such compounds inhibit spontaneously occurring, as well as pharmacologically (ACh, KCl, caffeine) or electrically (negative DC) evoked tonic and phasic activities in different smooth and oblique-striated muscles of snails [penis retractor muscle (PRM) of Helix], worms (torsos and muscle segments of Lumbricus and Eisenia) and mice (small intestine of Mus). In PRM preparations, experiments with the denervating drugs 6-OHDA, -5,6-DHT, and reserpine, or with the serotonergic receptor blocker methysergide, produced evidence that the herbicidal side-effect was not caused by action on the nervous system. 3. A relaxant effect on ACh-evoked contractions in the PRM was induced by drugs altering the Ca2+ equilibrium, for example, theophylline, papaverine, chlorpromazine, or trifluoperazine. 4. In addition, an extracellular Ca2+ deficiency or the presence of papaverine led to an enhancement of a CIPC-caused inhibition of ACh- or KCl-induced contractions. 5. The amplitudes of chemically evoked contractions in "skinned muscle cells" of Helix PRM or Lumbricus segments were influenced neither by CIPC nor by terbutryn. 6. CIPC was concentrated by the intact PRM and by a membrane containing PRM fraction, as well as by the worms' circular muscle system. 7. A fluorescent CIPC analogue, dansyl-3-chloroaniline, characterized by a similar inhibiting property on the induced contractions was detected at the border of PRM cells. 8. It is concluded that in the different muscle systems the side-effect of the herbicidal compounds is located in the outer muscle cell membrane where a Ca2+-dependent mechanism may be concerned. PMID- 2890496 TI - Esmolol. PMID- 2890497 TI - Preliminary report on a cooperative international study on sclerosing encapsulating peritonitis. PMID- 2890498 TI - Atrial natriuretic peptide (ANP), guanylate cyclase, and intraocular pressure in the rabbit eye. AB - Synthetic rat atrial natriuretic peptide (ANP) was examined for effects on guanylate-and on adenylate cyclase activity in ciliary process homogenates and for effects on intraocular pressure in the albino rabbit eye. Ciliary process guanylate cyclase was associated predominantly with the particulate fraction and was partially activated by ANP (EC50, approximately 1 nM) relative to a maximal dose of Na Nitroprusside (2 uM), whereas particulate adenylate cyclase (basal as well as forskolin-stimulated activity) showed no responses to ANP at doses up to 0.3 uM. Particulate cAMP phosphodiesterase activity was stimulated by low doses of cGMP (1-5 uM) in ciliary processes. Thus, ANP, acting via guanylate cyclase, has the potential to regulate phosphodiesterase activity and indirectly decrease cAMP levels in membranes derived from ciliary processes. Intravitreous injection of ANP (2-4 ug/eye) caused a small decrease (1-1.5 mm Hg) in intraocular pressure measured 16-24 hours after injection but the pressure had returned to normal by 40 hours. The findings demonstrate regulation of biochemical and pharmacological responses by ANP in the albino rabbit eye suggesting that this peptide may play a physiological role in secretory functions of ciliary processes. PMID- 2890499 TI - Toxic and allergic cutaneous reactions to jellyfish with special reference to delayed reactions. PMID- 2890500 TI - [Multiple endocrine neoplasia]. PMID- 2890501 TI - Glyburide decreases insulin requirement, increases beta-cell response to mixed meal, and does not affect insulin sensitivity: effects of short- and long-term combined treatment in secondary failure to sulfonylurea. AB - In 20 patients with non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to sulfonylurea, a double-blind randomized study was performed comparing two regimes: insulin plus placebo (IP) and insulin plus glyburide (IG). The protocol included two hospitalization periods (days 1-18 and 78-85) and follow-up at the outpatient clinic for 325 days. The metabolic control was kept as tight as possible. The subjects underwent normoglycemic clamp studies and meal tests with determination of insulin, C-peptide, glucagon, somatostatin, and gastric inhibitory polypeptide in plasma. On IG, they demonstrated marked and long lasting improvement of metabolic control: HbA1c decreased from 11.1 +/- 0.3% on day 3 to 8.3 +/- 0.4% (P less than .001) on day 78 and 9.1 +/- 0.5% (P less than .001) on day 325. In subjects on IP, the corresponding values were 10.3 +/- 0.5, 8.4 +/- 0.4 (P less than .001), and 8.9 +/- 0.5% (P less than .05). Body weight increased by 6.0 +/- 1.5 kg (P less than .005) on IG and 2.9 +/- 2.1 kg (NS) on IP. The daily insulin requirement decreased on IG from 62.5 +/- 12.9 U/day on day 7 to 33.5 +/- 8.8 U/day on day 83 and 34.6 +/- 8.9 U/day on day 325. On IP the insulin requirement was almost constant: 62.0 +/- 10.7 U/day on day 7, 55.5 +/- 7.7 U/day on day 83, and 54.7 +/- 7.9 U/day on day 325. Insulin sensitivity measured with the hyperinsulinemic clamp (plasma insulin approximately equal to 130 microU/ml) was similar on IP and IG at the initiation of the study and was unchanged on days 18 and 85. A key observation of this study, although the mechanism is unclear, is that isoglycemic-meal-related insulin requirement was diminished by insulin treatment, indicating improvement of meal-related insulin sensitivity. Glyburide increased basal and meal-but not glucagon-stimulated insulin and C-peptide levels, and also augmented the effect of meals on somatostatin release. We conclude that in NIDDM, IG regime promptly and continuously decreased insulin requirement and improved metabolic control. This effect is, at least during the first 3 mo, mainly due to enhanced insulin secretion. IG and IP treatment had no effect on insulin sensitivity during hyperinsulinemic-normoglycemic clamp, whereas meal-related insulin sensitivity was augmented. PMID- 2890502 TI - Chromosomal localization of the mouse homolog of the Huntington's disease linked G8 (D4S10) marker. AB - The human DNA probe G8 defines D4S10, a polymorphic locus tightly linked to the Huntington's disease gene on human chromosome 4. A subclone of G8, pSC33, showed significant cross-hybridization to discrete restriction fragments in total genomic mouse DNA. The probe detected restriction fragment length polymorphisms (RFLPs) with the enzymes Taq I and Msp I, permitting chromosomal localization of the mouse G8 homolog by linkage analysis using three sets of recombinant inbred mouse strains: BXH, BXD, and AKXD. The mouse locus was mapped to the central region of chromosome 11 at 1 centiMorgan from the SPARC gene, a locus whose human counterpart is on human chromosome 5. PMID- 2890503 TI - New murine homeoboxes: structure, chromosomal assignment, and differential expression in adult erythropoiesis. AB - The nucleotide sequence, chromosomal assignment, and preliminary transcriptional analysis of four murine homeoboxes is presented. Three of these are linked to the Hox-2 gene complex on chromosome 11, whereas the fourth, Hox-4, was assigned to mouse chromosome 12. A comparative analysis of homeobox sequences reveals that two of our sequences represent the previously described Hox-2.3 loci, whereas a third, mh19, could represent the predicted Hox-2.6 locus. Homeoboxes Hox-2.2 and Hox-2.3 are the cognates of two previously reported human homeoboxes that belong to a similar gene cluster on a closely related human chromosome (Chr 17), suggesting that homeoboxes may have been preserved as clusters during evolution. Moreover Hox-4, mh19, and the previously described Hox-1.5 homeobox form a separate subgroup of mammalian homeoboxes (90-92% amino acid and nucleotide homology). All four homeoboxes are expressed in the mouse embryo. Of special interest is the expression of mh19, a 4.2-kb transcript of which appears to be connected to the induced differentiation of Friend erythroleukemia cells. PMID- 2890504 TI - [Gamma-glutamyl transpeptidase-positive cells in esophageal abrasive balloon cytology and their clinical significance]. AB - gamma-glutamyl transpeptidase(gamma-GT) activity of cells from esophageal abrasive balloon cytocollection in 150 outpatients was detected and the characteristics of gamma-GT positive cells were studied in 107/150 cases. The gamma-GT positive cells may have been squamous cancer cells, dysplastic, hyperplastic or normal epithelial cells seen simultaneously or individually on a smear. The normal intermediate and superficial layer cells with positive gamma-GT were very frequently observed on the positive cytological smears. The hyperplastic and dysplastic cells were less frequently observed on the smear as compared with that of the high incidence area. Of 150 specimens, no cancer cells or gamma-GT activity was detected in 35; gamma-GT positive cells were observed in 70 out of 73 positive smears (95.9%); negative cancer cells and gamma-GT positive cells were seen in the rest 42. 25 of these 42 patients were followed and 19 became diagnosed as esophagus cancer by repeated abrasive balloon, biopsy or X ray examination. It is suggested that the persistent gamma-GT strongly positive cells be a signal of the existence of cancer. In other words, gamma-GT detection on the smears can be used as an adjuvant parameter in cytology to improve cytological diagnosis. PMID- 2890505 TI - Studies on the effects of pharmacological agents on antigen-induced arthritis in BALB/c mice. AB - The model of antigen-induced monoarticular arthritis in BALB/c mice, originally described by Brackertz et al. (1), has been examined with regard to disease pathogenesis and the activities of established antirheumatic agents. The acute phase of the arthritis, up to 7 days after intra-articular (IA) challenge, was characterized by intense polymorphonuclear leukocyte infiltration into the challenged joint, synovial lining cell hypertrophy and hyperplasia, accumulation of mononuclear cells within the subsynovial tissue, and pannus formation. Erosions of articular cartilage and bone commenced 7-14 days after IA challenge and progressed with time. Chronic synovitis was still evident 56 days after IA challenge. Prednisolone at 1 and 5 mg/kg, when administered against an established arthritis (dosing days 14-42), suppressed the histopathological changes. A similar level of suppression was observed when prednisolone was administered from days 0-42, indicating that the drug had no additional effect on the development phase of the arthritis. The non-steroidal anti-inflammatory agents (NSAIAs) indomethacin, ibuprofen and flurbiprofen failed to suppress either the established or developing disease. Daily treatment with D penicillamine, tiopronin or chloroquine on days 14-42 had no significant effect on the arthritis; treatment with either D-penicillamine or chloroquine on days 0 56 was also ineffective. When administered on days 14-42 or 0-42 neither gold thiomalate nor auranofin were able to suppress the erosive changes. Sulphasalazine (10-30 mg/kg) suppressed the arthritis whereas sulphapyridine was inactive. Azathioprine (20 mg/kg) suppressed the erosive changes when administered over days 14-42 or 0-42; this activity was associated with toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890506 TI - Structural modification of H2-receptor antagonists provide post-H2-receptor gastric antisecretory activity. AB - Structural analogues (e.g., Wy-46,499) of a known H2-antagonist (Wy-45,662) were found to inhibit acid secretion in the pylorus ligated rat and to block forskolin and DBcAMP-stimulated [14C]amino-pyrine (AP) uptake by rat isolated gastric mucosal cell preparations. Wy-45,662 (N-[3-[3-(1 piperidinylmethyl)phenoxy]propyl]thieno [3,4- d]isothiazol-3-amine 1, 1-dioxide), a very potent histamine H2-antagonist and antisecretory agent in the rat (ED50 approximately equal to 0.3 mg/kg), had no effect in vitro at 1 microM on forskolin-induced [14C]AP uptake while 10 nM Wy-45,662 completely suppressed histamine-stimulated [14C]AP uptake. In contrast, the N-benzylated form of Wy 45,662, Wy-46,499, dose-dependently (1 X 10(-7) -3 X 10(-6)M) suppressed forskolin-stimulated [14C]AP uptake while retaining modest antisecretory activity (ED50 approximately equal to 8 mg/kg) in vivo. Wy-46,499's modest antisecretory activity was thus attributable to inhibition via a post-histamine H2-receptor mechanism. PMID- 2890507 TI - Risk factors for alcohol hepatotoxicity among male alcoholics. AB - Alcoholic liver cirrhosis is a leading cause of morbidity and mortality in alcohol dependence. A common precursor to cirrhosis is alcoholic hepatotoxicity evident clinically by elevated serum liver enzymes. In this study 50 male patients with significant (greater than two times upper limits of normal) elevation of liver enzymes attending a veterans inpatient alcohol treatment center were matched by age and time since last drink to 50 male veterans without elevated liver enzymes. Patients with elevated liver enzymes were found to be more likely to be daily drinkers, less likely to indulge in binge drinking patterns or have alcoholic blackouts, and showed a trend towards a less severe pattern of alcoholism. Significant gamma glutamyl transferase (GGT) elevations were found in patients consuming an average of 7 beers/day for 5 years, and significant aspartate aminotransferase (AST) elevations were found in patients consuming a threshold of 12 beers/day for 10 years. These findings are consistent with current research suggesting alcoholic cirrhosis is a result of a threshold exposure to alcohol in alcoholics with an additional environmental or genetic risk factor. PMID- 2890508 TI - The influence of relapse rate on the choice of duodenal ulcer therapy. PMID- 2890509 TI - [Betablocker vs placebo in vasomotor headache. A double-blind crossover study]. AB - Vasomotor headaches are commonly, especially in the international literature, classified under ordinary migraine. Since beta-blockers seem to be the drug of choice in the prevention of migraine, 30 patients were given placebo and three times 40 mg propranolol in a double-blind cross-over trial. Among 24 fully assessable sets of tests only four showed a decrease in the frequency of headaches by more than 50%. In three patients the frequency actually increased over the placebo effect. PMID- 2890511 TI - [Poisoning with beta receptor blockers]. PMID- 2890510 TI - [Intracoronary thrombus in patients with unstable angina pectoris]. AB - Intracoronary thrombi were found in 20 of 52 patients (38%) who had coronary angiography because of treatment-resistant unstable angina. Unrelated to the angiographic finding, eight patients (15%) sustained a myocardial infarction, and two died during their hospital stay. Only one patient (5%) with and six patients (19%) without intracoronary thrombi were stabilized and discharged from hospital. The remaining patients either had an aortocoronary bypass (n = 31) or transluminal balloon angioplasty (n = 13). These findings underline the importance of intracoronary thrombus formation in the pathogenesis of treatment resistant unstable angina. PMID- 2890512 TI - [Jellyfish poisoning]. AB - While bathing in the Indian Ocean a 31-year-old German woman came into contact with a jelly-fish, probably of the species Chrysaora quinquecirrha. Initial signs were inflammatory cutaneous changes on the upper trunk, and both arms and feet. Over the next few days massive edematous swelling developed over the trunk, in addition to signs of arterial underperfusion in the hands and legs. Under treatment with urokinase and prostaglandin E1 the circulatory disorder in the feet completely disappeared. But the edema on the arms and hands got worse and huge bullae developed. On the assumption of a compartment syndrome a bilateral fasciotomy was performed. Wound healing proceeded normally. However, even after six months there remained extensive sensory and motor defects in both hands and arms. PMID- 2890514 TI - Drug treatment of phobias. Efficacy and optimum use. AB - In the last decade anxiety disorders have been the focus of intensive research in the psychiatric community, resulting in a rapid growth in our understanding of these illnesses. Diagnostic, biological, and psychopharmacological investigations have revealed important distinctions among these disorders which enable the clinician to make well-informed therapeutic choices and frequently ameliorate or even eliminate anxiety symptoms and related phobic behaviour. The principles of treatment can be simply stated: 1. Careful diagnostic evaluation through history and exclusion of medical and psychiatric conditions which mimic anxiety disorders. 2. Treatment selection based on diagnosis and formulation with the patient of the goals and expected outcome of pharmacotherapy. 3. Systematic application of each drug treatment in sufficient dosage and for an adequate duration permitting progression to the next agent when results are not optimal. 4. Addition of non-pharmacological interventions, usually behavioural therapy, to decrease phobic behaviour. 5. Development of a maintenance or discontinuation strategy tailored to the needs of the patient. PMID- 2890513 TI - Celiprolol. A preliminary review of its pharmacodynamic and pharmacokinetic properties and its therapeutic use in hypertension and angina pectoris. AB - Celiprolol is a new 'cardioselective' beta-adrenoceptor blocking drug with intrinsic sympathomimetic (partial agonist) activity and a weak vasodilating effect. Celiprolol appears not to cause bronchoconstriction or inhibit the effect of bronchodilating drugs in asthmatic patients and there is some evidence that it may have mild bronchodilating activity in such patients. Some studies suggest that celiprolol, because of vasodilation, may be less likely to reduce blood flow to the peripheries than other beta-adrenoceptor blocking drugs and hence cause fewer peripheral vascular side effects. Significant inhibition of exercise tachycardia occurs 24 hours after a single oral dose of celiprolol. In preliminary therapeutic trials celiprolol 200 to 600mg once daily was similar in efficacy to propranolol 40mg to 80mg twice daily or atenolol 100mg once daily in patients with mild to moderate hypertension or angina pectoris. If the apparent pharmacodynamic advantages of celiprolol are confirmed in well designed therapeutic trials then celiprolol should represent a definite advance in beta adrenoceptor blocking therapy. PMID- 2890515 TI - Somatostatin receptors on pituitary somatotrophs, thyrotrophs, and lactotrophs: pharmacological evidence for loose coupling to adenylate cyclase. AB - Pharmacological characterization of somatostatin (SRIF) receptors located on somatotrophs, thyrotrophs, and lactotrophs was attempted by measuring the effects of 14 structural agonists of somatostatin (SRIF) on the inhibition of basal and GRF-stimulated GH and basal and TRH-stimulated PRL and TSH secretion. We also checked the abilities of the analogs to displace [125I]N-Tyr-SRIF binding to pituitary cell membranes and their potency to inhibit adenylate cyclase activity. There was a very good correlation (r = 0.975) between the displacement of [125I]N Tyr-SRIF and the inhibition of adenylate cyclase activity by the analogs. The effects of the analogs on secretion of the three hormones followed the same rank order of potency. However, the active analogs displayed 2-6 times lower affinities in inhibiting PRL than GH or TSH secretions. The shift in affinity was even more pronounced in the case of the lower potency of the analogs as inhibitors of adenylate cyclase activity compared to hormone secretions. Pretreatment of the cells with pertussis toxin (100 ng/ml; 24 h) blocked SRIF inhibition of basal and GRF-stimulated adenylate cyclase activity and decreased by 83% [125I]N-Tyr-SRIF binding. It also blocked the ability of SRIF to inhibit GRF-induced GH and TRH-induced PRL and TSH secretion. However, pertussis toxin also increased GRF stimulation of GH secretion and decreased TRH stimulation of both TSH and PRL secretion. We conclude from our data that SRIF-binding sites located on the three target cells of the adenohypophysis are of a single class. These binding sites are negatively coupled to adenylate cyclase, but the inhibition of hormone secretions by SRIF cannot be explained solely through adenylate cyclase inhibition. Another mechanism of transduction must be involved in the actions of SRIF on its three pituitary target cells. PMID- 2890516 TI - Tissue-type plasminogen activator in somatostatin cells of rat pancreas and hypothalamus. AB - Plasminogen activators (PAs) proteolytically convert plasminogen to plasmin, which, in turn, can degrade most proteins. This system has been implicated in a variety of biological processes. Using immunocytochemical methods, we here describe the localization of tissue-type PA (t-PA) in rat somatostatin cells. In the pancreatic islets, a low number of strongly t-PA-immunoreactive cells was found. By sequential staining, we found these cells to constitute a subpopulation of the somatostatin cells. Biochemical analysis of extracts from isolated rat islets demonstrated the presence of t-PA, and immunoblotting analysis demonstrated one band with a similar electrophoretic mobility. No urokinase-type PA immunoreactivity was found in the rat endocrine pancreas. A granular t-PA immunoreactivity resembling that found in adjacent sections with somatostatin antiserum was found in the median eminence of the hypothalamus. No t-PA immunoreactivity could be detected in somatostatin cells of the gastric and intestinal mucosa. PMID- 2890517 TI - A case of von Recklinghausen's disease associated with pheochromocytoma and papillary carcinoma of the thyroid gland. AB - A 58-year-old woman was admitted to our hospital complaining of headache, dizziness and intermittent elevation of blood pressure. Multiple cafe-au-lait spots and neurofibromas had appeared on the back and the limbs since the age of 30 years. At the age of 54 years she underwent total thyroidectomy because of papillary carcinoma of the thyroid gland. On admission, the levels of plasma norepinephrine and epinephrine, urinary norepinephrine and normetanephrine were all within the normal range. However, urinary excretion of metanephrine was markedly increased to 1.49 +/- 0.45 (Mean +/- SD) mg/day and that of epinephrine was also slightly increased. The computed tomographic scans of the abdomen and the scintigraphy with 131I-metaiodobenzylguanidine revealed a tumor mass in the region of the right adrenal gland. The tumor was histologically confirmed to be pheochromocytoma at the operation. In her family history, her mother and one of her two sisters had von Recklinghausen's disease and another sister suffered from follicular carcinoma of the thyroid gland. As far as we know, this paper is the first report of a patient with von Recklinghausen's disease associated with both pheochromocytoma and non-medullary carcinoma of the thyroid gland, and her family. PMID- 2890518 TI - Pathogenesis and mechanism of traumatic injuries to teeth. PMID- 2890519 TI - Clathrin and coated vesicles. PMID- 2890520 TI - Exercise capacity, energy metabolism, and beta-adrenoceptor blockade. Comparison between a beta 1-selective and a non-selective beta blocker. AB - The effects of beta 1 and beta 1/2 blockade on exercise capacity were studied in 9 healthy normotensive subjects. Progressive maximal bicycle ergometer tests, followed by an endurance test at 80% of maximal work load, were performed during randomized, double-blind 3 day treatment periods with placebo, atenolol (beta 1) and oxprenolol (beta 1/2). The reduction of maximal work capacity (ca. 10%) was similar with atenolol and oxprenolol, despite a more pronounced maximal heart rate reduction with atenolol (from 175 +/- 2 to 132 +/- 3 beats.min-1) than with oxprenolol (to 138 +/- 2 beats.min-1). Exercise time during the endurance test was reduced from 36 +/- 4 min with placebo to 27 +/- 3 min with atenolol (p less than 0.05) and 24 +/- 3 min with oxprenolol (p less than 0.01) (atenolol vs. oxprenolol: p less than 0.05). During the endurance test, plasma glycerol and non esterified fatty acid concentrations were reduced with both atenolol and oxprenolol. The glycerol reduction was more pronounced with oxprenolol than with atenolol, plasma NEFA concentrations being similar. Plasma glucose and lactate concentrations were reduced by oxprenolol but not with atenolol. These data show that submaximal exercise capacity at work loads representing similar relative exercise intensities is reduced during non-selective and beta 1-selective beta blockade. This reduction may be related to the effects of beta 1 blockade on energy metabolism, with possibly an additional effect of beta 2 blockade. PMID- 2890522 TI - The Lopressor Intervention Trial: multicentre study of metoprolol in survivors of acute myocardial infarction. Lopressor Intervention Trial Research Group. AB - The Lopressor Intervention Trial (LIT) was a double-blind, randomized, placebo controlled, multicentre study designed to evaluate the effect of oral metoprolol on overall mortality in patients surviving a recent acute myocardial infarction. Patient enrollment began in August 1979 and ended on 15 April 1982, with 2395 patients (1200 on placebo and 1195 on metoprolol). Hospitalized patients, 45 to 74 years of age, began therapy from 6 to 16 days after their myocardial infarction. Following a short titration period, maintenance therapy with metoprolol 100 mg b.i.d. or placebo was continued for up to 1 year. Enrollment was prematurely terminated because of a progressive and marked decline in patient accession; it was not feasible to reach the original goal of 3200 patients in a practical period of time. This target sample size was based on an anticipated 1 year placebo mortality rate of 10%, a 50% reduction in total mortality with metoprolol and premature discontinuation of study medication in no more than 15% of patients in the metoprolol group. Two primary analyses were planned: total mortality among all randomized patients at 7 and at 12 months of trial entry. After 7 months of treatment there were 54 deaths in the placebo group and 42 deaths in the metoprolol group. After 1 year there were 62 deaths in the placebo group and 65 in the metoprolol group. Thus, the 1 year placebo mortality rate of 5.2% was half that predicted at the outset. In addition, study medication was prematurely discontinued in over 30% of patients in the metoprolol group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890521 TI - A D-mannose-specific lectin from Gerardia savaglia that inhibits nucleocytoplasmic transport of mRNA. AB - A new lectin has been isolated from the coral Gerardia savaglia by affinity chromatography, using locust gum as an absorbent, and D-mannose as eluant. Final purification was achieved by Bio-Gel P300 gel filtration. The agglutinin is a protein composed of two polypeptide chains with a Mr of 14800; the two subunits are not linked by disulfide bond(s). The isoelectric point is 4.8, the amino acid composition is rich in the acidic amino acids aspartic acid and glutamic acid. The absorption maximum for the protein was at 276 nm; with a molar absorption coefficient of 1.27 X 10(5) M-1 cm-1. The lectin precipitated erythrocytes from humans (A, B and O), sheep, rabbit and carp with a titer between 2(5) and 10(10); the affinity constant for lectin binding to sheep red blood cells was 2.8 X 10(8) M-1 and the number of binding sites, 3.2 X 10(5)/cell. Ca2+ ions are required for full activity; the pH optimum lies in the range between 6 and 11. Inhibition experiments revealed that the lectin is specific for D-mannose. The lectin is mitogenic only for those spleen lymphocytes from mice which had been activated by lipopolysaccharide. An interesting feature of this lectin is its ability to bind to glycoproteins present in nuclei from CV-1 monkey kidney cells. The fluorescein isothiocyanate-labelled lectin reacted with six polypeptides in the nuclear envelope from rat liver (Mr 190,000, 115,000, 80,000, 62,000, 56,000 and 42,000) and with two polypeptides in the nuclear matrix or pore complex lamina fraction (Mr 190,000 and 62,000). The lectin inhibited the nuclear envelope mRNA translocation system in vitro. It is suggested that this effect is due to an interaction of the lectin with the nuclear glycoproteins gp190 and/or gp62. PMID- 2890523 TI - Effect of beta-blockers on the relation between QT-interval and heart rate in exercise ECG. AB - QT-interval prolongation is a recognized risk indicator for ventricular arrhythmias and sudden cardiac death. The effect of beta-blockers on the change of the QT-interval relative to the change in heart rate was studied in 269 male patients who underwent computer-interpreted exercise tests. None of the patients studied used anti-arrhythmic drugs, diuretics or digoxin. In 141 men on beta blockers the relation between Q-peakT interval and heart rate could be described as follows: Q-peakT = -1.48 X heart rate + 415. In 128 patients not on beta blockers this relation was: Q-peakT = -1.14 X heart rate + 379. The difference of the slopes is 0.34 (0.22 - 0.46, 95% confidence interval). This difference was even more pronounced in a subgroup of coronary patients: 0.44 (0.30 - 0.57, 95% confidence interval). These results indicate that in men using beta-blockers the QT-interval shortens faster with increasing heart rate than in men not using them. At high heart rates patients on beta-blockers have a shorter QT-interval than those not using them. These observations could explain the beneficial effect of beta-blockers on exercise-induced ventricular arrhythmias and sudden death in coronary patients. PMID- 2890524 TI - Mechanism of action and efficacy of verapamil and beta-blockers in exercise induced ventricular tachycardia. AB - To determine the antiarrhythmic efficacy of beta-blockers (beta-B) and verapamil (V) in exercise-induced ventricular tachycardia (Ex-VT), nine patients with reproducible Ex-VT (in two consecutive exercise tests) were studied by means of electrophysiologic study (EPS) in basal conditions and serial exercise testing after beta-B (metoprolol 25 mg tid to 100 mg qid; oxprenolol 40 mg tid) and/or V (80-160 mg tid). Ejection fraction was normal in four cases and depressed in five. Of these nine patients, four developed Ex-VT during chronic amiodarone treatment, which was continued. During EPS, VT was induced at a critical atrial pacing rate in one case, and with the extrastimulus technique in four. Ventricular tachycardia was not inducible with either technique in four patients. Five of the six patients on beta-B and none of the seven on V developed Ex-VT, although they achieved the same or higher work-loads as compared to the basal exercise tests. In the case with rate-dependent VT, beta-B and V prevented VT at work-loads, sinus rates and double products significantly higher than those obtained in basal conditions. In the others, maximal heart rate and double product were lower on beta-B and showed a wide variability on V. V and beta-B appeared to be highly effective in preventing Ex-VT, in patients with normal heart as well as in those with greatly depressed ejection fraction. Both of the drugs appeared to suppress re-entry or triggered activity in the patient with rate-dependent Ex-VT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890525 TI - Opioid analgesia in extracorporeal shock wave lithotripsy: fentanyl versus alfentanil. AB - More than 1,600 patients have been treated by extracorporeal shock wave lithotripsy (ESWL) under fentanyl analgesia without any complications or severe side-effects. As secondary respiratory depression is still under discussion, we investigated the value of alfentanil--a short-term acting opioid--with special interest in its efficacy and side-effects. Neither fentanyl nor alfentanil significantly influenced blood pressure, respiratory rate and blood gases. With regard to minor side-effects and patient's acceptance, alfentanil analgesia should be preferred during ESWL treatment. PMID- 2890526 TI - Unilaterally impalpable testis. AB - Thirty children presenting with a unilateral impalpable testis and a normally descended contralateral testis underwent surgical exploration. The testis was absent ('vanishing testis') in 12 cases (40%) and orchidectomy for a dysgenetic testis was performed in a further 5 cases. The overall rate of monorchism following surgery was therefore 56%. It is desirable that parents be advised of this possibility pre-operatively. PMID- 2890527 TI - Comparison of antitumor activity of standard and investigational drugs at equivalent granulocyte-macrophage colony-forming cell inhibitory concentrations in the adhesive tumor cell culture system: an in vitro method of screening new drugs. AB - We compared the in vitro growth inhibition of primary human tumor cells in the adhesive tumor cell culture system (ATCCS), exposed to the investigational agents caracemide, spirogermanium and taxol and to standard chemotherapy agents at equitoxic concentrations for granulocyte-macrophage colony-forming cells (GM-CFC) in vitro. Clinically active standard agents tested at up to GM-CFC 90% inhibitory concentrations (IC90) resulted in in vitro activity (greater than or equal to 50% tumor growth inhibition) in at least 30% of tumors tested. In vitro responses for taxol, caracemide and spirogermanium were 78%, 9% and 7%, respectively. This paper proposes a model that incorporates two hypotheses: (1) myelotoxic drugs which inhibit tumor growth at concentrations equal to or less than equitoxic GM CFC ICs will demonstrate clinical activity; and (2) both myelotoxic and particular nonmyelotoxic drugs inactive in vitro at these doses will not be active clinically. If this drug screening concept is valid, taxol may be clinically more active than caracemide and spirogermanium. PMID- 2890528 TI - Identification of intrathymic T progenitor cells by expression of Thy-1, IL2 receptor and CD3. AB - Immature (L3T4-/Lyt-2- "double-negative") thymocytes were separated into several functionally distinct fractions based on their expression of IL2 receptors, Thy-1 and CD3. The majority (60-70%) of double-negative thymocytes in young adult mice lack detectable IL2 receptor expression, have high levels of Thy-1 and rapidly "progress" to a L3T4+ or L3T4+/Lyt-2+ stage when cultured for 20 h in simple medium. In contrast, the IL2 receptor-positive fraction retains the double negative phenotype for as long as it survives in culture and addition of IL2 has little or no effect on such cells. IL2 does generate strong proliferation from a fraction of cells expressing low levels of Thy-1, but not detectable IL2 receptors. Such culture generates an unusual population of double-negative cells that expresses the pan-B cell molecule B220 and which kill both the NK target cell line YAC-1 and the NK-resistant line EL4. This Thy-1-low fraction includes all of the double-negative thymocytes capable of T cell reconstitution. Thy-1-low fraction could be further separated into two populations with regards to CD3 expression. CD3- but not CD3+ population could reconstitute mature T cells, indicating that Thy-1-low, IL2R- and CD3- cells are the most enriched population of intrathymic T cell progenitors. PMID- 2890529 TI - Mott cells: a model to study immunoglobulin secretion. AB - Mott cells are plasma cells defective in immunoglobulin (Ig) secretion. They display this defect by accumulating Ig in the rough endoplasmic reticulum, detectable by Ig+ intracellular inclusion. We have previously produced hybridoma cell lines (Alanen, A. et al., Eur. J. Immunol. 1985. 15: 235) in which this phenotype is preserved, and shown the inability of these cells to secrete the Ig. In order to study this defect further, we fused these hybridoma cells with a kappa-secreting hybridoma cell line, Sp1, and, using double selection with hypoxanthine, aminopterin, thymidine and ouabain, obtained hybrid cell lines expressing various combinations of the three Ig chains involved (Mott gamma 1, Mott kappa and Sp1 kappa chains). We studied the presence of Ig+ inclusions in these cells as well as Ig secretion by metabolic labeling and immunoprecipitation. All inclusion-positive clones expressed both Mott heavy and Mott light chains with or without the Sp1 light chain, whereas none of the inclusion-negative clones produced both Mott-derived Ig chains. In all of the clones, even those with inclusions, the Ig secretion was at least partially rescued by the fusion. This occurred also in an inclusion-positive clone which maintained the original Ig status of the Mott without Sp1 kappa chain, indicating a complementation by the cell fusion of some cellular factor involved in Ig secretion. Furthermore, we injected Xenopus oocytes with mRNA isolated from three different original Mott cell hybridomas and could show secretion of the Ig, which is not secreted from the original Mott cells, from the oocytes. PMID- 2890530 TI - Anti-Thy-1-induced proliferation of immature thymocytes expressing the CD3 associated gamma/delta heterodimer. AB - A series of rat monoclonal antibodies (mAb) directed against the Thy-1 molecule have been evaluated for their ability to stimulate immature (CD4-8-) murine thymocytes. CD4-8- thymocytes could be induced to proliferate by several anti-Thy 1 mAb provided that exogenous interleukin 1 or interleukin 2 was provided. Apparently non-stimulatory anti-Thy-1 mAb could be rendered stimulatory if cross linked by a rabbit anti-rat immunoglobulin reagent. Anti-Thy-1-stimulated CD4-8- thymocytes were found to uniformly express CD3 but did not stain positively with F23.1, a mAb reactive with alpha/beta T cell receptors utilizing the V beta 8 gene family. Immunoprecipitation analysis of such stimulated CD4-8- thymocytes indicated that they expressed a CD3-associated heterodimer of 45 kDa/35 kDa most likely corresponding to the product of the gamma and (putative) delta T cell receptor genes. Taken together, these data demonstrate that anti-Thy-1 mAb selectively activate a subset of CD4-8- thymocytes committed to the gamma/delta T cell receptor lineage. PMID- 2890531 TI - Antagonism by E. coli endotoxin of some cardiovascular effects induced in the rat by two alpha 2-adrenoceptor agonists. AB - E. coli endotoxin (0.01, 0.1 and 1 microgram/kg i.v.) 1 h before alpha 2 adrenoceptor agonists B-HT 933 and clonidine (i.v.) antagonized their bradycardiac and hypotensive effects in intact rats. This antagonism seems not to depend on the presence of the adrenal glands since similar results were obtained in adrenalectomized rats. Endotoxin at higher doses (1 and 10 micrograms/kg) suppressed the hypotensive and reduced the bradycardiac effect of clonidine injected i.c.v. (5 micrograms/kg). In contrast, endotoxin (up to 100 micrograms/kg) did neither increase arterial pressure nor heart rate in the pithed rat. This suggests the participation of a central site of action for endotoxin. However, E. coli endotoxin (1, 10 or 100 micrograms/kg) did not decrease the inhibition by clonidine of the tachycardia induced by stimulation of the cardioacceleratory nerve. This excludes peripheral presynaptic alpha 2 adrenoceptor blockade by endotoxin. Only 100 micrograms/kg decreased the pressor response to clonidine in the pithed rat. These results show that E. coli endotoxin is a potent modificator of the cardiovascular regulation in the rat. It antagonized central alpha 2-adrenoceptor mediated cardiovascular effects at doses lower than those acting on postsynaptic peripheral alpha-adrenoceptors. PMID- 2890532 TI - The role of lysyl oxidase and collagen crosslinking during sea urchin development. AB - Lysyl oxidase, the only enzyme involved in collagen crosslinking, is shown to be present in embryos of the sea urchin Strongylocentrotus purpuratus. The enzyme specific activity increases over six-fold during development, showing the greatest rise during gastrulation and prism larva formation. The enzyme is inhibited by the specific inhibitor, beta-aminoproprionitrile (BAPN). Continuous BAPN treatment of S. purpuratus and Lytechinus pictus embryos from late cleavage stages onward increases the amount of noncrosslinked collagen present in prism larvae. When BAPN is added at the 128- or 256-cell stage it causes developmental arrest at the mesenchyme blastula stage. Embryos can be maintained in the arrested state for at least 96 h and will resume normal development and morphogenesis following BAPN removal. If BAPN is added after the mesenchyme blastula stage, it has little adverse effect on development; consequently nonspecific toxic effects of the drug are unlikely. The results suggest that lysyl oxidase and collagen crosslinking play a vital role in primary mesenchyme migration, gastrulation, and morphogenesis during sea urchin development and indicate that BAPN may be very useful in studying the extracellular matrix-cell interactions at the cellular and molecular level. PMID- 2890533 TI - Evidence for a role of the hepatic endocytic compartment in the modulation of the extracellular matrix. AB - The presence of fibronectin in rat liver endocytic compartment was investigated using biochemical and immunological approaches. Three endosome subfractions were separated from postmitochondrial lysosome supernatants using sucrose and isoosmotic Nycodenz gradients. Using these endosomes the presence of fibronectin in the "early" and "late" endosome subfractions and in a receptor-enriched fraction was demonstrated by Western blot analysis. Furthermore, immunofluorescence studies using an anti-rat fibronectin antiserum and an anti rat endosome antiserum showed similar patterns of staining in frozen liver sections. The results indicate that the components of the extracellular matrix extend into the endocytic compartment and suggest that fibronectin is internalised in a manner similar to that of some plasma membrane proteins. PMID- 2890534 TI - Nephropathia epidemica: incidence of clinical cases and antibody prevalence in an endemic area of Sweden. AB - The incidence of nephropathia epidemica (NE) was compared with the NE antibody prevalence in normal population in a highly endemic area of Sweden (Vasterbotten county). The antibody prevalence rate in the oldest age groups were found to be 14 and 20 times higher than the accumulated life-risk of being hospitalized with NE for men and women respectively. Whether the infection in persons not admitted to hospital is subclinical, atypical or clinically fulminant, remains to be determined. PMID- 2890535 TI - Adult T-cell leukemia following long-term remission from non-Hodgkin's lymphoma. AB - A female patient who had been initially diagnosed with non-Hodgkin's lymphoma (NHL) and achieved complete clinical remission with combined chemotherapy, developed overt adult T-cell leukemia (ATL) after 9 yr of disease-free survival. This is the first case of the development of ATL following the complete remission of NHL. Secondary malignant neoplasms are not well-documented in patients previously diagnosed with Hodgkin's disease. Although there have been a few reports concerning the occurrence of secondary malignancy in patients with non Hodgkin's lymphoma (NHL), there has never been a documented case of ATL following long-term survival from NHL. Here, we report a case of typical adult T-cell leukemia (ATL) which occurred after 9 yr disease-free survival from NHL. PMID- 2890536 TI - A first case of complete remission of beta-interferon sensitive adult T-cell leukemia. AB - A case of complete remission of adult T-cell leukemia (ATL) induced by beta interferon is reported. A 46-year-old male was diagnosed as ATL because of the increased number of ATL cells with deeply indented and lobulated nuclei in the peripheral blood, accompanied by elevated values of the lactic dehydrogenase, the alkaline phosphatase, and the calcium in the serum. The result of the cell surface marker analysis of peripheral blood lymphocytes was compatible with ATL and anti-ATL associated antibody (ATLA) was positive. The integration of proviral deoxyribonucleic acid (DNA) of human T-cell leukemia virus type I(HTLV-I) was proved in the peripheral blood lymphocytes using Southern blot hybridization. Since an ordinal chemotherapy was not so effective for this patient, he was treated with 1.8 X 10(7) units of recombinant beta-interferon (beta-IFN) per day for 7 days as one course. After 5 courses of treatment, a markedly favorable response was recognized, and he achieved complete remission. A lower dose of beta IFN (9 X 10(6) units per day for 3 days as one course, one or two courses per month) has been continued and he has still been in a complete remission state for 10 months. It is concluded that beta-IFN should be used to treat ATL. PMID- 2890537 TI - Induction and activation of tissue transglutaminase during programmed cell death. AB - During the involution of lead nitrate-induced hyperplasia in rat liver a significant increase of transglutaminase activity, enzyme concentration, transglutaminase messenger RNA and protein-bound epsilon-(gamma-glutamyl)lysine (product of transglutaminase action) coincided with programmed death (apoptosis) of hepatocytes. Immunohistochemical examination showed the appearance of transglutaminase in apoptotic hepatocytes. An increased transglutaminase level was also detected during glucocorticoid-induced apoptosis of rat thymocytes. PMID- 2890538 TI - Transmembrane proton-motive potential of Spiroplasma floricola. AB - In Spiroplasma floricola, the transmembrane proton-motive potential delta p was studied. It is composed of a transmembrane electric potential difference, delta psi, and a transmembrane proton gradient, delta pH, according to delta p = delta psi - (Z.delta pH). Using a potential-sensitive carbocyanine dye and 5,5' dimethyl[2-14C]oxazolidine-2,4-dione as probes, delta psi and delta pH were measured at different [H+] of the medium, and delta p was calculated to be remarkably constant at -123 mV +/- 16% over a wide range of external pH values. Inhibition experiments indicated that it is generated by a membrane-bound, electrogenic, proton-translocating ATPase. PMID- 2890539 TI - Somatostatin and calcitonin modulate gastropod internal defense mechanisms. AB - Immunoreactive somatostatin and calcitonin are stored in selected mammalian leukocytes. Synthetic somatostatin and calcitonin can alter the functional activity of certain mammalian blood cells. These findings suggest that the two enteroneuro-peptides serve as modulators of the mammalian immune system. The aim of the present study is to determine whether the 2 peptides are also found in gastropod blood cells and whether they may participate in the regulation of the gastropod internal defense mechanisms. We found that somatostatin-like and calcitonin-like substances are located in a distinct population of hemocytes from the pond snail Physella heterostropha and that the amount of immunoreactive calcitonin in hemocytes increases after an injury to the body wall. Synthetic somatostatin and calcitonin stimulate the attachment of latex beads to in vitro cultured hemocytes. We conclude that the somatostatin- and calcitonin-like substances may serve as modulators of the internal defense system of gastropods. PMID- 2890540 TI - Effects of arginine and arginine plus somatostatin infusion on insulin release in diabetic patients submitted to pancreas allotransplantation. AB - The present study was aimed at evaluating the role of the Autonomic Nervous System (ANS) in the insulin (IRI) response to arginine in humans. Nine patients who were recipients of simultaneous segmental pancreatic and renal grafts (6 receiving steroids and azathioprine as immuno suppression therapy, 3 treated with Cyclosporine A), 3 non-diabetic patients with kidney grafts (receiving steroid and azathioprine) and 10 normal subjects were studied. Arginine induced a clear IRI release in all subjects with no significant difference among the groups. Somatostatin (SRIF) inhibited IRI release to a similar degree in all subjects. Since the transplanted pancreas is completely denervated, these data suggest that the integrity of the ANS is not essential to the IRI response to arginine, nor for the inhibitory effect of SRIF on IRI release. PMID- 2890541 TI - Differential effects of sodium butyrate and dimethylsulfoxide on gamma-glutamyl transpeptidase and alkaline phosphatase activities in MCF-7 breast cancer cells. AB - Sodium butyrate and dimethylsulfoxide (DMSO), two known chemical inducers of cell differentiation, were examined on MCF-7 breast cancer cells. Both agents reduce the proliferative capacity of MCF-7 cells, as reflected by inhibition of colony formation in semisolid agar. Sodium butyrate is shown to enhance markedly the activity of two plasma membrane-bound enzymes, alkaline phosphatase and gamma glutamyl transpeptidase. DMSO does not enhance the activity of these enzymes, but rather induces a small decrease in gamma-glutamyl transpeptidase activity. The present results show that although both agents inhibit cell proliferation, they have a distinct effect on phenotypic expression. PMID- 2890543 TI - Weak estrogenic activity of phenol red in the culture medium: its role in the study of the regulation of prolactin release in vitro. AB - Phenol red, which is commonly used in culture media as a pH indicator, has recently been shown to possess estrogenic properties. In this study we investigated the effects of phenol red on prolactin release and synthesis by cultured female and male rat anterior pituitary cells and on the sensitivity of these cells of dopamine, TRH and somatostatin (SRIF). It was shown that phenol red stimulated rat prolactin release and cell content in a dose-dependent manner. The effects of 30 microM phenol red, which is the medium concentration in our regular culture medium, and a submaximally active concentration of 17 beta estradiol (E2) were additive. Male rat pituitary cells were far more responsive to phenol red and also to E2 than female pituitary cells. The antiestrogen tamoxifen (100 nM) significantly inhibited the phenol red-stimulated prolactin release by male rat pituitary cells but caused a 2-fold increase of prolactin release in the absence of phenol red. 30 microM phenol red did not modulate the responsiveness of female and male rat lactotrophs to dopamine, TRH or SRIF. We propose from our results that the estrogenic effect of 30 microM phenol red is too weak in order to alter the responsiveness of rat lactotrophs to dopamine, TRH and SRIF but the presence of phenol red in culture media should be considered when the effects of estrogens and antiestrogens on rat prolactin release and synthesis in vitro are studied. PMID- 2890542 TI - Effects of a preparation containing a standardized ginseng extract combined with trace elements and multivitamins against hepatotoxin-induced chronic liver disease in the elderly. AB - A preparation containing a standardized ginseng extract which has been shown to exert anti-hepatotoxic activity in vitro, combined with trace elements and multi vitamins was compared to placebo in 24 elderly out-patients with toxin-induced (alcohol and drugs) chronic liver disease in order to evaluate its effect on liver function. Each patient was blindly treated either with the preparation containing ginseng extract or placebo for 12 weeks. The preparation containing ginseng extract significantly modified bromsulphthalein retention and blood zinc levels when compared to pre-treatment levels and to placebo. Serum bile acids, and gamma-glutamyl transpeptidase before and after a fatty meal were significantly reduced after treatment with the test preparation and not with placebo. When the two treatment groups were compared, however, no significant difference in these parameters was observed. These results suggest that treatment with the preparation containing ginseng extract could improve the detoxifying activity of the liver in elderly patients with toxin-induced chronic liver disease. PMID- 2890544 TI - Extracellular matrix changes PC12 cell shape and processing of newly synthesized dopamine. AB - PC12 cells on extracellular matrix (ECM) or plastic were incubated with 3H tyrosine (3H-TY) in the presence and absence of serum or cold tyrosine. 3H Dopamine (3H-DA) was determined in medium and cells from 1 to 48 h later with Dowex cation exchange chromatography. In serum-free and tyrosine-free medium, PC12 cells on ECM released significantly more 3H-DA, whereas cells on plastic had a significantly higher cellular content of 3H-DA, but total 3H-DA (medium plus cells) was equal in ECM and plastic cultures. When 3H-TY was added to tyrosine containing medium, there was a significant decrease in the levels of 3H-DA detected and the differences between ECM and plastic cultures were attenuated, but the patterns of secretion and storage were similar to those observed with tyrosine-free medium and total synthesis did not decline at 48 h. Serum decreased the efficiency of the resin to retain 3H-DA from culture medium, attenuated the difference in dopamine release between ECM and plastic cultures, and contributed to variations in 3H-TY uptake. The morphometric relationship between the cell membrane and the internal compartment in PC12 cells of different shapes was also characterized. The perimeter length and area of the midsection of cells were determined with a modular system for quantitative digital analysis. The perimeter length of cells on ECM was significantly greater than cells on plastic, whereas the internal areas were similar. The ratio of perimeter length to area (P/A) for all cells on ECM was 30% higher than the P/A ratio for cells on plastic. The ratio of P/A for a subpopulation of very flat cells on ECM was 70% higher than the ratio for round cells on plastic. Immunocytochemistry for tyrosine hydroxylase revealed a more diffuse distribution of this enzyme in cells on ECM. These data suggest that there is an increase in the ratio of cell surface area to cell volume as PC12 cells spread on ECM which could facilitate secretory vesicle fusion with the cell membrane, and hence, exocytosis. Although there is a concomitant increase in the secretion of dopamine and a decrease in the storage of dopamine, the change in cell shape does not appear to immediately alter the synthesis of dopamine. PMID- 2890545 TI - Cell cycles and in vitro transdifferentiation and regeneration of isolated, striated muscle of jellyfish. AB - Isolated, mononucleated, cross-striated muscle cells of a medusa can transdifferentiate in vitro to various new cell types and even form a complex regenerate. The transdifferentiation events follow a strict pattern. The first new cell type resembles smooth muscle and is formed without a preceding DNA replication. This cell type behaves like a stem cell and by quantal cell cycles produces all other new cell types. Some preparations develop an inner and an outer layer separated by a basal lamella. Formation of these layers does not depend on DNA replication. When layers do not form, each division results in nerve cells and smooth muscle cells. If separation into layers occurs, then a regenerate will be formed, and in the course of only two cell cycles all necessary cell types to form a functional regenerate will differentiate. PMID- 2890546 TI - Reduction of gastric acidity with ranitidine or famotidine: early evening dosage is more effective than late evening dosage. AB - The antisecretory effect of a once daily dose of ranitidine and famotidine was examined after administration of the drugs either immediately after dinner or 3 h after dinner. A placebo-controlled multiple cross-over study was performed in 7 healthy ambulatory volunteers. They were given, on 6 separate days at least 1 week apart, either placebo, ranitidine 300 mg or famotidine 40 mg, either immediately after dinner or 3 h later. Breakfast, lunch and dinner were standardized. 24-Hour intragastric acidity was measured with a combined glass electrode. Duration of secretory inhibition by a drug was defined as the nighttime period between the first rise of pH above and the final fall below 3.5. This value represents the 95% upper confidence limit of nighttime pH values during placebo treatment. Secretory inhibition with early and late administration of ranitidine lasted for 10.7 and 7.3 h, respectively (p = 0.012). With famotidine it lasted for 10.1 and 7.1 h, respectively (p = 0.005). Gastric acidity after dinner was decreased by early but not late intake of ranitidine and famotidine. Thus, both ranitidine and famotidine were more effective when taken early, immediately after dinner, than when taken late in the evening. This observation might affect the mode of ulcer treatment with these drugs. PMID- 2890547 TI - The effects of hyperglycaemia on isotopic measurement of glucose utilisation using [2(3)H], [3(3)H] and [6(14)C] glucose in patients with type 1 (insulin dependent) diabetes mellitus. AB - To determine whether hyperglycaemia alters the accuracy with which [2(3)H] and [3(3)H]glucose reflect glucose turnover measured with [6(14)C]glucose in patients with Type 1 (insulin-dependent) diabetes mellitus, glucose utilisation rates were measured during a simultaneous infusion of [2(3)H], [3(3)H] and [6(14)C]glucose after maintenance of normoglycaemia overnight and when glucose concentrations were clamped at 5.3, 7.5 and 9.7 mmol/l while insulin and glucagon concentrations were held constant. Glucose utilisation rates determined with all three isotopes were comparable in the diabetic patients at all glucose concentrations studied. On the other hand, glucose utilisation rates in nondiabetic subjects determined with [6(14)C]glucose were greater (p less than 0.01) than those determined with [3(3)H]glucose and lower (p less than 0.04) than those determined with [2(3)H]glucose during the 5.3, 7.5 and 9.7 mmol/l clamps. Nevertheless, glucose utilisation rates in the diabetic patients were lower (p less than 0.05) than those in the nondiabetic subjects for each glucose isotope. We conclude that hyperglycaemia does not alter the pattern of metabolism of [2(3)H] or [3(3)H]glucose in patients with Type 1 (insulin-dependent) diabetes mellitus. PMID- 2890548 TI - [Effect of sub-bacteriostatic doses of aztreonam on the adhesion of Pseudomonas aeruginosa]. AB - The effect of sub-inhibitory concentrations of Aztreonam towards the adhesiveness of an uropathogenic strain of P. aeruginosa was tested. The filamentous forms, morphologically altered by the action of the antibiotic, were not capable of adhering to human uroepithelial cells. This phenomenon was due to an alteration of bacterial structures responsible for the adhesion and was not related to a steric hindrance caused by the antibiotic on either the bacterial structures or the cell receptors. PMID- 2890549 TI - Glutamate and related acidic excitatory neurotransmitters: from basic science to clinical application. AB - There is convincing evidence that acidic amino acids, in particular L-glutamate, or substances containing them serve as the major excitatory neurotransmitters in the brain. At least three distinct receptors mediate the excitatory effects of this class of neurotransmitters. Pharmacological studies with agonists and antagonists of these receptors suggest that they may mediate the neurodegenerative consequences of Huntington's disease, status epilepticus, and hypoxemia, and that glutamate receptor antagonists have clinical potential as anticonvulsants, analgesics, and neuroprotective agents. PMID- 2890550 TI - Olsalazine sodium in the treatment of ulcerative colitis among patients intolerant of sulfasalazine. A prospective, randomized, placebo-controlled, double-blind, dose-ranging clinical trial. AB - Sixty-six outpatients with active ulcerative colitis who were intolerant of sulfasalazine were treated in a double-blind randomized trial. They received placebo or olsalazine sodium in daily doses of 0.75, 1.5, or 3 g. Overall, 35% of patients receiving olsalazine improved clinically, compared to 16% of patients receiving placebo. When the colitis activity at study entry was compared with that observed at the completion of the study period, statistically significant or nearly significant improvement was demonstrated within the combined olsalazine group (p = 0.01) and within patient groups receiving olsalazine at daily doses of 1.5 g (p = 0.04) and 3 g (p = 0.055). A dose-response relationship was suggested because 16%, 29%, 27%, and 50% of patients improved in the placebo and 0.75-, 1.5 , and 3-g olsalazine groups, respectively, (p = 0.04). A similar pattern of improvement was seen when sigmoidoscopic criteria were used, although a dose response relationship was not demonstrated. There were no differences between the treatment and placebo groups for any of the adverse effects or laboratory variables reported at baseline or during the trial period. Four patients were withdrawn because of adverse reactions: 2 developed a skin rash while receiving olsalazine and 2 had diarrhea, one while on olsalazine and the other while on placebo. The data suggest that olsalazine is effective for the treatment of ulcerative colitis and is well tolerated among patients intolerant to sulfasalazine. PMID- 2890551 TI - Neurohormonal regulation of gastrointestinal immunity. PMID- 2890553 TI - A trans-acting suppressor restores splicing of a yeast intron with a branch point mutation. AB - Splicing of introns from Saccharomyces cerevisiae pre-mRNA requires the conserved sequence TACTAAC; the 3'-most A residue is utilized as the site of branch formation. We showed previously that the transcript from an actin-HIS4 gene fusion containing the mutation TACTAAC to TACTACC (designated C259) is spliced inefficiently, thereby preventing growth on the histidine precursor histidinol. By selecting for growth on histidinol, we have identified a mutant in which the splicing of the C259 transcript is increased fourfold; splicing of other mutated introns is not significantly improved. The mutant locus encodes a trans-acting suppressor. A single mutation, rna16-1, is sufficient for suppression; however, suppression is maximized in heterozygous diploids containing both rna16-1 and the wild-type allele RNA16. In addition, wild-type pre-mRNAs (and lariat intermediates) accumulate in rna16-1 cells. We propose that the RNA16 locus encodes a component of the splicing machinery. PMID- 2890552 TI - Sequences in the pea rbcS-3A gene have homology to constitutive mammalian enhancers but function as negative regulatory elements. AB - The pea rbcS-3A gene, which codes for a key component of the photosynthetic machinery, requires light for its expression. Analysis of chimeric constructs in transgenic tobacco plants has shown that a 280-bp fragment from the 5' noncoding region can act as a light-inducible transcriptional enhancer. Further characterization of this enhancer identifies a 58-bp sequence containing two regulatory elements that can decrease transcription in the dark. One has a high degree of homology to the SV40 core enhancer, the other to the adenovirus 5 E1A enhancer and the constitutive part of the human interferon-beta gene enhancer. Deletion of the 58-bp sequence uncovers additional light-responsive elements (LREs) located further upstream and downstream. PMID- 2890554 TI - Expression of a homeo domain protein in noncontact-inhibited cultured cells and postmitotic neurons. AB - The murine Hox 1.3 gene is one of six homeo box genes clustered on chromosome 6. Our analysis of Hox 1.3 cDNA and genomic clones indicates that the gene is organized into two exons and encodes a 270-amino-acid homeo domain protein. The predicted protein is rich in serine, glycine, and proline residues, and its homeo domain is identical to the Hox 2.1 domain. During embryogenesis, the gene is maximally expressed at midgestation but is also expressed to a lesser extent in many adult tissues possessing different cell lineages. Hox 1.3 transcripts are also present in cultured fibroblasts. The Hox 1.3 protein accumulates in the nuclei of nonconfluent cultured fibroblasts but is greatly diminished in contact inhibited nongrowing cells. Thus, the expression of the Hox 1.3 gene correlates with growth in embryos and cultured cells. Paradoxically, it is also expressed in certain subsets of postmitotic, fully differentiated neurons, most notably the Purkinje neurons of the cerebellum, the pyramidal and dentate neurons of the hippocampus, and the motor neurons of the spinal cord. This complex pattern of expression suggests that Hox 1.3 may provide a function required by many cell types in addition to any role it may have in morphogenesis. PMID- 2890555 TI - Use of repetitive sequences to identify DNA polymorphisms linked to regA, a developmentally important locus in Volvox. AB - The regA locus plays a centrally important role in Volvox development by preventing somatic cells from redifferentiating as germ cells; until now, approaches to cloning regA, as a preliminary to molecular analysis of its function, have been lacking. Here a novel approach is described that uses repetitive-sequence probes to rapidly identify restriction fragment length polymorphisms (RFLPs) linked to regA. Genomic DNA was cut with restriction enzymes having 4-base recognition sequences and then electrophoresed long enough to run most fragments off the gel; the remaining long (1- to 20-kb) fragments were resolved into numerous, reproducibly identifiable bands. On Southern blots of such preparations, six repetitive-sequence probes were used to identify 1232 bands, 24% of which were polymorphic between two closely related strains. Ninety four RFLPs, for which inheritance patterns have been analyzed, fall into 36 "segregation groups," within which no recombination was observed in the limited progeny sample analyzed. Eight RFLPs cosegregated perfectly with alleles at the mating-type (mt) locus. More significantly, four RFLPs exhibited linkage to the regA locus, providing a potential starting place for a chromosome walk designed to clone the locus. PMID- 2890556 TI - Geriatric hypertension: antihypertensive therapy in coronary artery disease. AB - Systemic hypertension is a common clinical problem in the elderly. There is emerging evidence to suggest that with careful utilization of antihypertensive drugs, blood pressure can be lowered in the elderly population. Whether isolated systolic hypertension should be treated aggressively remains an unanswered question despite the evidence that systolic hypertension can cause certain cardiovascular complications. An elderly patient with hypertension and concomitant coronary artery disease merits proper blood pressure control with appropriate drugs to prevent progression of coronary disease. The therapeutic objective is not only to lower the blood pressure but to accomplish this goal with drugs which are likely to have a favorable effect on coronary artery disease. Changing trends in the drug therapy of hypertension indicate that calcium antagonists and beta-blocking drugs offer a therapeutic advantage in elderly hypertensive patients with coronary artery diseases. PMID- 2890557 TI - Somatostatin in the elderly: diurnal plasma profile and secretory response to meal stimulation. AB - Plasma somatostatin levels were determined during a 24-hour period and after a meal test in 7 and 5 elderly subjects (76-90 years), respectively. The data obtained were compared with those recorded in young adult subjects (22-30 years). Increased basal somatostatin values were found in elderly subjects (20.0 +/- 1.5 pg/ml) when compared to young adults (14.1 +/- 0.6 pg/ml; p less than 0.01). Also, the mean 24-hour somatostatin levels were higher in the elderly (21.3 +/- 0.8 pg/ml) than in young adults (16.7 +/- 0.5 pg/ml; p less than 0.01), and minor diurnal variations were found in the former group. The response to the meal test was less evident in the elderly than in the control group. The data obtained indicate an increased basal somatostatin production associated with a diminished variability throughout the 24-hour period and in relation to meals. PMID- 2890558 TI - Alterations of humoral, cell mediated and antibody dependent cell mediated cytotoxic responses during the course of amoebic infection in guinea pigs. AB - The cellular and antibody dependent cellular cytotoxic (ADCC) responses of splenic lymphocytes and peritoneal macrophages obtained from animals at variable intervals after inoculation were studied against trophozoites of axenic E histolytica (NIH:200). Cytotoxic responses of effector cells from infected animals were compared with those of effector cells from vaccine stimulated and unstimulated uninfected control animals. Cellular and antibody-dependent cellular cytotoxic responses of the effector cells from animals during the establishment and acute phase of infection were significantly suppressed, compared with unstimulated uninfected and vaccinated (FI amoebic proteins stimulated) effector cells. The effector cells from animals recovered from infection showed enhanced cytotoxic responses against trophozoites of E histolytica. The suppressed cytotoxic response was accompanied by impairment of cytotoxic cell activities and lack, or very low level of anti-FI antibodies in the sera of animals during the establishment phase of infection. With the rise in anti-FI antibodies in the sera of animals ADCC could be induced effectively against trophozoites of E histolytica, which seem to result in clearance of amoebic infection. PMID- 2890559 TI - Organ culture of rabbit ileum as a model for the investigation of the mechanism of intestinal damage by enteropathogenic Escherichia coli. AB - Organ culture of rabbit ileum has been established as a model for the investigation of the mechanism of intestinal damage by enteropathogenic Escherichia coli (EPEC). Loops of rabbit ileum were filled in vivo with saline, non-enteropathogenic P-fimbriate E coli (PFEC), or EPEC. After 45 minutes the loops were washed, then mucosal biopsies were taken and cultured for up to 48 hours. The earliest changes discernable by electron microscopy were observed at 18 hours postinfection, at which time EPEC were closely adherent to the surface of enterocytes at the base of microvilli, some of which were elongated. By 24 hours postinfection there were large areas of brush border effacement with pedestal formation around the EPEC. No such damage was seen in biopsies from the control loops (saline, PFEC), and intracellular ultrastructure was extremely well preserved in all preparations for up to 48 hours. While there were no differences at eight hours, biochemical analyses at 24 hours postinfection showed a marked increase in the release of brush border enzymes into the culture medium from EPEC infected explants compared to explants from the control loops. These findings provide morphological and biochemical evidence for damage to the microvillus membrane by EPEC, and validate organ culture of rabbit ileum as a model for the investigation of EPEC-pathogenicity. PMID- 2890560 TI - A mixed endocrine adrenal tumour causing steatorrhoea. AB - A 60 year old man developed steatorrhoea, weight loss, mild diabetes mellitus, labile hypertension and limb cramps. Raised plasma concentrations of catecholamines, particularly noradrenaline and a computed tomography-scan showing an adrenal tumour strongly suggested a pheochromocytoma. Adrenoreceptor blockade reversed the symptoms, decreased faecal fat, and increased duodenal trypsin to normal concentrations. After adrenalectomy the patient was asymptomatic and there was no steatorrhoea. The blood glucose concentrations became normal. Immunocytochemistry revealed the tumour cells to store large amounts of enkephalin and somatostatin reactive material and moderate amounts of immunoreactive beta-endorphin and dynorphin. PMID- 2890561 TI - Acid suppression in duodenal ulcer: a meta-analysis to define optimal dosing with antisecretory drugs. AB - FVMany different dosage schedules of antisecretory drugs for the treatment of duodenal ulcer are recommended. The relationship between degree of acid suppression and therapeutic efficacy has not been precisely defined for these drugs. We have examined the association between suppression of intragastric acidity and duodenal ulcer healing rates for a number of therapeutic regimens. For the H2 receptor antagonists alone, the most significant correlation with healing rates was with suppression of intragastric acidity at night (r = 0.926; p = 0.0001). When other classes of drug: high dose antacid, omeprazole and a synthetic prostaglandin (enprostil) were included in the analysis, the closest correlation was with suppression of total 24 hour intragastric acidity (r = 0.911; p less than F0.0001). Stepwise linear regression analysis was used to investigate the relative contributions to healing of suppression of acidity during the day and night. Suppression of nocturnal acidity was found to be the single most important factor in explaining healing rates. No further benefit was obtained with daytime suppression for H2 receptor antagonists; suppression of acidity at night accounted for 86.1% of the observed variation in healing rates among different regimens of H2 receptor antagonists. When all classes of drugs were analysed, inclusion of daytime suppression produced a significant improvement in correlation over nocturnal suppression alone. Drug regimens providing potent suppression of nocturnal acidity produce the highest healing rates in controlled clinical trials. The healing rate for any dose regimen of an antisecretory drug can be predicted from a knowledge of its effect on intragastric acidity. For the H2 receptor antagonists, suppression of nocturnal acidity is the most relevant in this context. Moderate suppression of acidity achieves ulcer healing rates at four to eight weeks which are comparable with those seen with potent suppression at two to four weeks. Increasing degrees of suppression merely accelerate healing. PMID- 2890562 TI - [Effects of antiallergic agents on polymorphonuclear leukocytes. The inhibition of arachidonic acid release and superoxide production]. AB - The aim of this study was to examine the effects of antiallergic agents on the functions of polymorphonuclear leukocytes (PMNs) in terms of its arachidonic acid release and superoxide-anion generation. The stimulations of arachidonic acid release by formyl-methionyl-leucyl-phenylalanine (FMLP) were effectively diminished by 20 microM of azelastine as well as clemastine. Challenges of 20 microM and 50 microM of these agents inhibited approximately 50% and 100% of the arachidonic acid release, respectively. On the contrary, inhibitions of over 50% were not caused by cromoglycate, chlorpheniramine and diphenhydramine at concentrations up to 50 microM. The potency of the above examined drugs on the superoxide generations from PMNs were similar to the effects of arachidonic acid release. Ketotifen, however, showed intermediate effects indicating that a challenge of 50 microM ketotifen inhibited approximately 50% of the arachidonic acid release without having an effect on the superoxide generation. These experimental observations suggested that one of the important roles of the antiallergic agents including azelastine (known as a chemical mediator release inhibitor) and clemastine (known as a histamine H1 receptor antagonist) could be an inhibition of the first step of the arachidonic acid cascade. PMID- 2890564 TI - Proceedings of the third annual summer meeting of the American Orthopaedic Foot and Ankle Society. July 17-19, 1987, Sante Fe, New Mexico. Abstracts. PMID- 2890563 TI - Effects of toxic doses of a novel histamine (H2) antagonist on the rat thyroid gland. AB - The oral administration of high doses of a histamine H2 antagonist SK&F 93479 (up to 1000 mg/kg/day) to male rats for up to 21 days resulted in alterations in thyroid morphology indicative of increased activity of the thyroid gland. Measurement of thyroidal 125I incorporation substantiated these findings. Treatment with SK&F 93479 resulted in a dose-dependent increase in thyroidal iodide incorporation. This was apparent after a single dose of the compound and was reversible after dosing for 7 days. The increased incorporation of 125I into the thyroid gland was apparently dependent on thyroid-stimulating hormone (TSH) since both hypophysectomy and pretreatment with thyroxine (T4) markedly reduced thyroidal 125I uptake. Hypothalamic thyrotropin-releasing hormone (TRH) and pituitary TSH concentrations were not altered by SK&F 93479 treatment, and in TRH challenge experiments circulating TSH concentrations showed no change from control levels. These data suggest that hypothalamic-pituitary sensitivity was unaltered by treatment with SK&F 93479. Pharmacological ablation of thyroidal mast-cell function did not alter the thyroid response to 125I accumulation after SK&F 93479 dosing, indicating that the action of the compound is probably not dependent on changes in thyroid mast-cell histamine. Circulating T4 and TSH levels were altered in SK&F 93479-treated rats. Generally, T4 levels were reduced 6 hr after dosing and TSH levels were elevated 24 hr after dosing. Triiodothyronine (T3) levels were unaffected by SK&F 93479 treatment. The effect of SK&F 93479 treatment on T4 clearance was measured by examining the elimination of radioactivity from the circulation of rats previously injected with 125I labelled T4. One oral dose of 1000 mg SK&F 93479/kg markedly increased T4 clearance. These results suggest that SK&F 93479 affects thyroid activity indirectly by a primary effect on T4 clearance. Reductions in circulating T4 lead to increased TSH levels and subsequent stimulation of thyroid activity. PMID- 2890565 TI - Inpatient treatment of complicated agoraphobia and panic disorder. AB - Despite recent advances in the treatment of agoraphobia and panic disorder, some patients do not respond to standard outpatient regimens of biological and psychosocial intervention and may require more intensive, closely supervised care. The authors describe a specialized inpatient program that integrates pharmacotherapy, intensive levels of exposure and other behavioral therapies, a structured and strategically reinforcing environment, panic and anxiety management strategies, and other interventions designed specifically for patients with complicated panic-based disorders. Outcome data for 25 patients indicate that after a mean stay of 35 days, 19 patients were significantly improved. These preliminary results suggest that appropriately designed inpatient programs offer an effective treatment option for some patients with refractory conditions of agoraphobia or panic disorder. PMID- 2890566 TI - Segmental Takayasu (giant cell) aortitis with rupture and limited dissection. AB - Takayasu arteritis is a chronic inflammatory disease of the aorta and its main branches, with variable extents of involvement. Rarely is it sharply localized in an isolated segment of the aorta, and it seldom occurs in an elderly person. Clinically, Takayasu arteritis produces symptoms of vascular insufficiency, predominantly because of the occlusive disease and less commonly because of aneurysmal disease of the affected arteries. An unusual case of segmental Takayasu arteritis confined to the infrarenal abdominal aorta in an elderly woman is described, in which rupture and fatal hemoperitoneum were the initial manifestations of the disease. PMID- 2890567 TI - Leydig cells within the aspermatogenic seminiferous tubules. AB - Cells identical to Leydig cells were found within a peritubular boundary layer and even inside a basal lamina of seminiferous tubules in three male patients (two with inguinal cryptorchism and one with infertility). The seminiferous tubules of all patients showed a moderate to marked thickening of the boundary layer and a complete loss of spermatogenic cells. The "ectopic Leydig cells" were characterized by the presence of Reinke crystals or an extensively developed smooth endoplasmic reticulum. These cells were believed to have differentiated in situ from myoid cells within the boundary layer and also to have invaded from the interstitial tissue in the form of mature Leydig cells. The occurrence of ectopic Leydig cells appeared to parallel the extent of loss of the Sertoli cells and also that of the thickening of the boundary layer. The functional significance of the ectopic occurrence might be implicated in the impaired spermatogenesis. PMID- 2890569 TI - Linkage relationships of X-linked choroideremia to DXYS1 and DXS3. AB - Choroideremia is a distinct blinding condition with an X-linked pattern of inheritance. We have analyzed two RFLPs, DXS3 and DXYS1, for linkage with the choroideremia locus (TCD) within three kindreds. A maximum LOD score of 3.98 was obtained at theta = 0.14 for TCD:DXS3. The summed maximum LOD score from this study and from previously published TCD:DXYS1 data is 5.23 at theta = 0.05. Contrary to previous reports, the present data demonstrate that these two RFLPs are not tightly linked to the choroideremia gene locus. PMID- 2890568 TI - The Kidd (JK) blood group locus assigned to chromosome 18 by close linkage to a DNA-RFLP. AB - The close linkage between the PstI-restriction fragment length polymorphism (RFLP) disclosed by the L2.7 genomic DNA probe and the Kidd blood group locus is described. The maximum lod score is +8.53 at recombination fraction theta = 0.03. The upper probability limit of the recombination fraction is theta 1 = 0.11. The L2.7 probe, previously assigned provisionally to chromosome 17, is by the present study assigned to chromosome 18. This also assigns the Kidd blood group locus (JK) to chromosome 18. Accepting previous deletion mapping, the shortest regions of overlap (SRO) for JK is 18q11-12, whereas one of our hybrids assigns L2.7 to 18p11-pter, suggesting centromeric localisation of the linkage group. JK has been assigned previously to chromosome 2 because of its provisional linkage to IGK which in turn has been mapped to 2p12. Our own JK-IGK linkage data do in fact support the previous positive lod scores at high recombination fractions (total lods +4.12 at theta1 = 0.30). No obvious explanation for the conflicting gene mapping data is found. PMID- 2890570 TI - Anderson Fabry disease, a close linkage with highly polymorphic DNA markers DXS17, DXS87 and DXS88. AB - Anderson Fabry disease is an X-linked lysosomal storage disorder caused by alpha galactosidase A deficiency. Hemizygous males and some heterozygous females develop renal failure and cardiovascular complications in early adult life. We have investigated six large UK families to assess the possible linkage of five polymorphic DNA probes to the Anderson Fabry locus, previously localised to Xq21 24. No recombination was found between Anderson Fabry disease and DXS87, DXS88 and DXS17, which gave lodmax = 6.4, 6.4 and 5.8 respectively at theta = 0.10, (upper confidence limit 0.10). DXS3 gave lodmax 2.9 at theta = 0.10 (upper confidence limit 0.25). DXYS1 was excluded from linkage. The best fit map (DXYS1/DXS3) theta = 0.192 (DXS17/DXS87/DXS88/Anderson Fabry locus) provided no information about the order of loci in parentheses due to the absence of recombinants. The close linkage of DXS17, DXS87 and DXS88, together with alpha galactosidase A estimation, can be used for antenatal diagnosis and carrier detection until the application of a gene specific probe has been evaluated. PMID- 2890571 TI - Familial deletion in Becker type muscular dystrophy within the pXJ region. AB - A family of an isolated patient with Becker muscular dystrophy has been investigated by DNA analysis. Southern blotting and hybridization were performed with six probes (C7, pERT87.15, pERT87.1, pXJ1.1, pXJ2.3, 754) mapping in the Xp21 region. A deletion within the pXJ region was demonstrated in the proband, his mother and all three sisters. The segregation pattern for the restriction fragment length polymorphisms (RFLPs) observed with the pXJ probes as well as with pERT87.15, pERT87.1 and 754 probes indicates that the deletion is of grandpaternal origin. PMID- 2890572 TI - Four DNA polymorphisms on the short arm of the X chromosome: allele frequencies in a German and in a Turkish population. AB - Four restriction fragment length polymorphisms, revealed by cloned arbitrary X chromosome segments (L1.28, RC8, pD2, 754) were studied in samples (50 individuals each) of a German and a Turkish population. All previously reported alleles of these polymorphisms were found in both populations, except the infrequent RC8 allele B3 (3.0 kb fragment), which was absent in both groups. The observed minor alleles were found to be rarer in the German series than in the Turkish group, but there was no conclusive evidence of essentially different allele frequencies in either population. However, the frequencies of the RC8 allele B2 (5.3 kb fragment) were differing at the 5% significance level. The allele frequencies of the four polymorphisms are presented and compared with those reported from other European regions. PMID- 2890574 TI - Cooperation between T and B cells. A minimal model. PMID- 2890573 TI - A role for IFN-gamma and NK cells in immune responses to T cell-regulated antigens types 1 and 2. AB - Responses to antigens that have been previously recognized as T cell-independent are now known to be dependent on some form of T-cell (or T cell-derived) help. This T-cell dependency, however, can be most easily noted when responses to small resting B cells are examined, since responses of larger, size-separated B cells to TNP-Ficoll require little if any T-cell help. The type of ancillary "help" that is required for the responses to type 1 and type 2 antigens exhibits certain similarities as well as differences. Thus, responses to both of these antigens can be stimulated in the presence of L3T4- or L3T4+ cells as well as in the presence of IL2. However, while the presence of IFN-gamma may be significantly inhibitory for the responses to the type 2 antigen TNP-Ficoll, they do not appear to influence the response to the type 1 antigen TNP-BA. Furthermore, while vigorous elimination of NK cell activity from purified B-cell populations enhances the response to TNP-Ficoll, it has no discernible effect on the response to TNP-BA. These results suggest that determination of type 1 and type 2 antigens may be made not only based on the characteristics of the carrier molecule but also on the nature of ancillary help that needs to be provided for these antigens to stimulate optimal responses. Type 1 antigens have polyclonal B-cell activating properties and stimulate responses which are not influenced by IFN-gamma, type 2 antigens have no polyclonal B-cell activating properties and stimulate responses which can be influenced by IFN-gamma. PMID- 2890575 TI - Molecular genotyping of the HLA-DQ alpha gene region. AB - Restriction fragment analysis has been applied to genomic DNA extracted from human tumor cell lines. Polymorphic restriction fragments encompassing the HLA-DQ alpha gene were observed upon digestion with Bgl II, Eco RI, and Hind III. Analysis of these polymorphic fragments (or allogenotopes) showed that for each restriction enzyme a series of three differently sized allogenotopes existed. Clusters of cosegregating allogenotopes belonging to the different allelic series defined three different allogenotypes. Each allogenotype exhibited a distinctive restriction map generated by digestion with five restriction enzymes. Comparison of these restriction maps showed that generation of the polymorphisms observed at the HLA-DQ alpha region in these sets of cell lines is not caused by a single event. In some B- and T-lymphoma cell lines a fourth allogenotype was found. The restriction site map of genomic DNA from these cell lines suggested that the latter distribution of restriction enzyme sites was most probably generated by recombination between two of the previously observed allogenotypes at a crossover site(s) adjacent to the HLA-DQ alpha gene. PMID- 2890576 TI - Association of membranous nephropathy with T-cell receptor constant beta chain and immunoglobulin heavy chain switch region polymorphisms. AB - We have investigated T-cell antigen receptor constant beta chain genes (Tcr C beta) and immunoglobulin (Ig) heavy chain switch region genes of HLA-DR-typed patients with membranous nephropathy (MN) employing DNA restriction fragment length polymorphism (RFLP) analysis. When a Tcr C beta probe in conjunction with the restriction endonuclease Bgl II was used, a significant increase in the frequency of a 10.0; 9.2 kb heterozygous RFLP phenotype was found in MN (75.0% versus 42.1% in controls; P = 0.002). When Sst I-restricted DNA from MN patients was hybridized with a DNA probe homologous to the switch region flanking the Ig C mu heavy chain gene (S mu), there was a significant decrease in the frequency of the 2.1; 2.6 kb heterozygous RFLP phenotype in MN (24.0% versus 54.6% in controls; P = 0.004). These results suggest that Tcr beta and Ig heavy chain loci, as well as HLA antigens, may be important in the pathogenesis of MN. PMID- 2890577 TI - T-cell receptor VT beta genes in natural populations of mice. AB - The composition of 15 VT beta gene subfamilies has been examined by Southern hybridization among a broad spectrum of colony bred rat and mouse species extending phylogenetically from Rattus to Mus musculus domesticus. Most mouse species contain a similar content of VT beta genes as determined by the number of hybridizing restriction fragment (RF) bands. Furthermore, the extent of restriction fragment length polymorphism (RFLP) appears to be limited. Some VT beta gene families, however, are missing from Rattus (VT beta 7, VT beta 12) and M. shortridgei (VT beta 9, VT beta 16). Extension of the VT beta survey to a panel of 38 wild caught mice reveals that nearly a third lack specific hybridization to the VT beta 5 probe. Previous reports have established that the mouse inbred strains SJL, C57BR, C57L, and SWR lack 50% of their VT beta repertoire, including VT beta 5 (Behlke et al. 1985). This study demonstrates that natural populations of mice also carry a significantly reduced VT beta gene repertoire. PMID- 2890578 TI - HLA-DR, DQ, and DX alpha RFLPs and their associations with serologically defined HLA-DR and -DQ antigens. PMID- 2890579 TI - Lipidic nitrosating agents produced from atmospheric nitrogen dioxide and a nitrosamine produced in vivo from amyl nitrite. AB - In studies on nitrosating agent(s) formed in skin of mice exposed to nitrogen dioxide, we showed that: (i) N-nitrosomethylaniline was produced in skin of mice exposed to nitrogen dioxide and then painted with N-methylaniline; (ii) a nitrosating precursor in methyl linoleate is associated with peroxidation products; (iii) cholesterol is a major nitrosating precursor in mouse skin, probably because it produces the nitrosating agent, cholesteryl nitrite; (iv) cholesteryl nitrite enhances autoxidation of lipids in vivo and on mouse skin and, like sodium nitrite, catalyses the autoxidation of iodide; (v) N nitrosomethylaniline was produced in mice injected intraperitoneally with methylaniline and gavaged with amyl nitrite; and (vi) nitrosating agents may occur normally in human skin lipids. PMID- 2890580 TI - Molecular dosimetry of DNA alkylation during chronic exposure to carcinogens. AB - Incorporation of the molecular dosimetry of DNA adducts is being proposed as a means for placing quantitative risk assessment on a stronger scientific basis. While this is likely to be an improvement over straight mathematical extrapolation, we believe that a more holistic approach that incorporates even more biology is needed. Therefore, we have begun to quantify the dose-response relationships for N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis by characterizing the major promutagenic DNA adduct, O4-ethyldeoxythymidine (O4 etdT); hepatocyte proliferation; and hepatocyte initiation in rats continually exposed to drinking-water containing NDEA. The results show that O4-etdT accumulates to apparent steady-state concentrations that are proportional to dose at all but the highest exposures, at which less than linear amounts are found. This appears to be due to excessive cytotoxicity, since hepatocyte proliferation is markedly increased at high but not at low exposures. Hepatocyte initiation, as determined by the presence of gamma-glutamyl transferase-positive foci, appears to have limitations in sensitivity that preclude investigations at low exposures. These methods may provide valuable insight into mechanisms of hepatocarcinogenesis at moderate exposures. Collecting these data should help to identify endpoints that may be relevant for human risk assessment. PMID- 2890581 TI - Structure and physiological actions of rat atrial natriuretic factor. AB - Natriuretic substances were purified from rat atrium (atrial natriuretic factor, ANF) and were shown to be identical with the inhibitor of norepinephrine-induced contraction of smooth muscle. Four native forms were isolated and their amino acid sequences were determined. The presence of a high-molecular-weight prohormone was shown. Complementary DNA (cDNA) encoding for the precursor was cloned and used to deduce the amino acid sequence of the prohormone. Genomic DNA for ANF was cloned and two introns were found. Several ANF peptides were synthesized. Structure-function studies showed that the ring structure was essential for the activity. Antibodies produced against the synthetic 25-amino acid residue ANF were used to develop a radioimmunoassay. The presence of ANF in rat plasma demonstrated that ANF is a circulating hormone. ANF was also found in the hypothalamus of rats. The ANF in plasma was found to be a low-molecular form, whereas that in atria and hypothalamus consisted of both the high-molecular weight precursor and low-molecular-weight active ANF. The presence of messenger RNA for ANF was determined using ANF cDNA as a probe and was considered as evidence for ANF synthesis in the brain, atrium, and ventricles. ANF was shown to be released from the brain. ANF administered intracerebroventricularly was shown to inhibit angiotensin II and thirst-induced dipsogenesis. In vitro and in vivo experiments showed ANF inhibits release of vasopressin from posterior pituitary and renin from the kidneys. The hypotensive effect of ANF was examined at various doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890582 TI - Isolation and function of a Clostridium perfringens enterotoxin fragment. AB - A fragment was obtained by treating Clostridium perfringens enterotoxin with 2 nitro-5-thiocyanobenzoic acid, a reagent which specifically cleaves the amino terminal peptide bond of cysteine residues. The fragment (molecular weight, 15,000) was purified by high-performance liquid chromatography. The fragment had no cytotoxic effect on Vero cells but competitively inhibited enterotoxin-induced 51Cr release. Binding of 125I-labeled fragment to Vero cells was comparable to that of enterotoxin. Moreover, 125I-labeled fragment did not bind to FL cells, which lack receptor for enterotoxin. We conclude that the fragment contains the binding domain of enterotoxin. The amino acid composition of the fragment suggests that it is located on the carboxyl-terminal part of enterotoxin. PMID- 2890583 TI - Adherence of Salmonella typhimurium to small-intestinal enterocytes of the rat. AB - The adherence of radiolabeled Salmonella typhimurium to freshly isolated enterocytes of rats was studied. The results established that type 1 fimbriated strains adhered in significantly higher numbers than did related nonfimbriated strains. Adherence was inhibited by D-mannose and methyl alpha-D-mannoside. Results of kinetic studies indicated that adherence was biphasic; the number of bacteria that adhered per enterocyte remained constant for approximately 20 min and then increased rapidly under the assay conditions. The second phase was associated with structural damage to the enterocytes. The addition of chloramphenicol did not prevent the initial attachment of bacteria to enterocytes but did prevent the second phase. Viable and nonviable bacterial cells adhered to enterocytes, but only viable bacteria were destructive. Freshly isolated enterocytes (trypan blue impermeable) and enterocytes stored overnight (trypan blue permeable) were infected by viable S. typhimurium in a similar manner, suggesting that metabolic activity of the host cell was of less consequence than metabolic activity of the bacterial cells. A model for the role of mannose sensitive fimbriae as a virulence factor is proposed. PMID- 2890584 TI - In vivo emergence of enterotoxigenic Escherichia coli variants lacking genes for K99 fimbriae and heat-stable enterotoxin. AB - Neonatal pigs were inoculated with porcine enterotoxigenic Escherichia coli 431, which carries genes for K99 fimbriae and STaP enterotoxin. Colonies of strain 431 were recovered from feces of pigs for up to 17 days after inoculation and tested for hybridization with gene probes for K99 and STaP. Variants of strain 431 that did not hybridize with the probes were considered to have lost the genes. Variants were recovered from 10 of 13 suckling pigs that survived the infection. Only 0.4% of the isolates recovered during the first 2 days after inoculation were variants. Of the isolates recovered 3 to 5 days after inoculation, 20 to 36% were variants. Variant colonies were detected more frequently among pigs in some litters than in others. The litter with the highest number of variant-shedding pigs had the dam with the highest titer of K99 antibody in her colostrum. Variants also occurred in colostrum-deprived, artificially reared pigs. However, the number of variants detected was lower and they occurred later in the course of the infection in colostrum-deprived pigs than in suckling pigs. More variants were detected and they were detected earlier in colostrum-deprived pigs fed anti K99 monoclonal antibody than in controls fed anti-K88 monoclonal antibody. Loss of STaP appeared to be secondary to loss of K99 in that some variants lacked only K99 (K99- STaP+) and some lacked both genes (K99- STaP-), but none was of the K99+ STaP- type. Our results confirmed reports of gene loss from enterotoxigenic E. coli during infection. They are consistent with the hypothesis that variants emerge under in vivo selection pressure of K99 antibody and with the speculation that gene loss may be an important component of protection in vaccinated populations. However, the emergence of variants did not appear to play a major role in the recovery of individual pigs from clinical disease. PMID- 2890586 TI - Molecular cloning of the Escherichia coli O75X adhesin. AB - The uropathogenic strain Escherichia coli IH11128 (O75:K5:H-) exhibits a mannose resistant O75X adhesin. The genes encoding the O75X adhesin were cloned from a clinical strain and transferred to E. coli K-12 derivatives. The recombinant plasmids were found to express a 15-kilodalton fimbrial subunit protein, a fimbrialike extracellular structure, and mannose-resistant hemagglutination. An indirect immunofluorescence assay was used to study attachment of the clone and purified adhesin to frozen sections of human kidney. The clone bound selectively to the interstitial areas and notably to Bowman's capsule. The purified adhesin bound to the basement membrane of the tubules and to Bowman's capsule. PMID- 2890585 TI - Polyclonal B-cell-activating factors produced by spleen cells of mice stimulated with a cell homogenate of Trypanosoma gambiense. AB - The effect of injection of a cell homogenate of Trypanosoma gambiense into mice on the production of soluble factors responsible for the induction of polyclonal B-cell activation (PBA) by their spleen cells was examined. PBA was induced by injection of the cell homogenate and was also detected in mice treated with either the serum or the spleen cells of mice treated with the cell homogenate. PBA-inducing activity became detectable in the serum and spleen cells as early as 12 h after injection of the cell homogenate, reached a peak on day 2, and then decreased. This activity was also detected in the culture medium of spleen cells obtained 2 days after injection of the cell homogenate. For determination of the type of spleen cells producing the PBA-inducing factor, the day 2 spleen cells were fractionated on the basis of differences in their adhesive properties. Spleen cells in the effluents from a Sephadex G-10 column (T and B cells) and a nylon wool column (T cells) and those adhering to a plastic flask (macrophages) all produced the PBA-inducing factor. The production of PBA-inducing factor by whole spleen cells and by cells adherent to the plastic flask was not affected by treatment with anti-Thy-1.2 antibody and complement. These data suggest that soluble factors derived from macrophages and T cells could contribute to the induction of PBA. The PBA-inducing activity in the conditioned medium was completely inactivated by treatment at pH 2.0, heating at 56 degrees C for 30 min, or exposure to 0.1% sodium dodecyl sulfate. The results are discussed in relation to cytokines that could affect B-cell activation. PMID- 2890587 TI - Phospholipase D activity of Vibrio damsela cytolysin and its interaction with sheep erythrocytes. AB - Exposure of sheep erythrocytes to sublytic amounts of Vibrio damsela cytolysin markedly reduced their membrane sphingomyelin content and their sensitivity to lysis by the sphingomyelin-dependent cytolysins staphylococcal sphingomyelinase C (beta-toxin) and helianthin. The toxin was found to be a phospholipase D active against sphingomyelin. PMID- 2890588 TI - Altered HLA antigens expressed on T and B lymphocytes of adult T-cell leukemia/lymphoma patients and their relatives. AB - The HLA types of peripheral blood lymphocytes (PBL) of 36 adult T-cell leukemia/lymphoma (ATLL) patients were examined and compared with those of 45 healthy relatives of these patients, and with those of 10 non-ATLL families including 80 healthy members. Thirty-one percent of ATLL patients showed either a gain or a loss of HLA antigens determined by the presence of alien HLA antigens or the absence of inherent HLA antigens deduced from familial haplotype analysis. The antigen specificity of HLA gained or lost was variable and differed from case to case among ATLL patients. Although the gain of HLA was detected only in ATLL patients, the loss of HLA was found both in ATLL patients and in asymptomatic healthy relatives. The rate of HLA loss in ATLL patients (8.4%) and their relatives (17.8%) was much higher than in relatives of non-ATLL patients (1.1%). The HLA gain and loss revealed in the PBL of ATLL patients were confirmed by altered HLA phenotypes in the cloned T and B cells established from ATLL patients. Our results suggest that latently infecting HTLV-I may induce altered HLA phenotypes in T and B cells, primarily with loss of HLA antigens in a population of asymptomatic virus carriers, and secondarily with a gain of HLA antigens after the development of ATLL. PMID- 2890589 TI - Haemodynamic dose-response actions of cicloprolol in left ventricular dysfunction due to ischaemic heart disease. AB - Cicloprolol is a cardioselective beta-1 partial agonist; its haemodynamic and radionuclide (nuclear stethoscope) effects were determined in 22 patients with impaired left ventricular function due to coronary artery disease. Following a 20 min stable control period, the effects of four doses of cicloprolol (0.025, 0.025, 0.05 and 0.1 mg/kg at 10 min intervals) were measured at rest 5-10 min after each intravenous injection. The effects of the cumulative 0.2 mg/kg dosage were assessed during supine bicycle exercise and compared with a control exercise period. At rest there were significant increases in systolic arterial without change in mean blood pressure. The heart rate and cardiac index were unchanged. There was a significant increase in left ventricular ejection fraction with a reduction in filling pressure and volume. Patients with resting heart rate below 75 beats/min and with ejection fraction greater than 35% showed the greatest improvement. During supine bicycle exercise, ejection fraction was increased compared to control (31 +/- 2 to 36 +/- 2; P less than 0.01), cardiac volume reduced and exercise tachycardia attenuated. These data suggest that cicloprolol may be of value where beta-blockade is considered in the presence of underlying left ventricular dysfunction due to ischaemic heart disease. PMID- 2890590 TI - A comparison of psychotropic drug use between the general population and clients of health and social service agencies. AB - The purpose of this research was to study the epidemiology of psychotropic drug use among the general population and to draw comparisons to drug use among clients of medical, mental health, and social services in the same jurisdiction. Results showed considerably higher percentages of users for all drug categories among agency clientele. Age and sex differences in drug use replicated previous research in the general population but were noticeably absent among the clients of local services. Notably, the proportion of long-term daily users of minor tranquilizers in the agency population was about three times that of the general population. However, tranquilizer users in the two populations were similar in many respects. Results of the study are discussed in terms of the need for screening for persons with psychotropic drug problems in health and social services. PMID- 2890591 TI - Long-term antihypertensive therapy with beta-blockers: submaximal exercise capacity and metabolic effects during exercise. AB - The effects of long-term (6 months) antihypertensive treatment with three different types of beta-blockers (propranolol, nonselective without ISA; pindolol, nonselective with ISA; metoprolol, beta 1-selective without ISA) on submaximal exercise capacity and metabolic variables during submaximal endurance exercise were studied in seven subjects with essential hypertension. Exercise tests were performed on a bicycle ergometer at 70% of estimated VO2 max. Similar reductions of resting and exercise blood pressure and exercise heart rate were obtained with the three beta-blockers. Exercise time was significantly reduced by all three beta-blockers during chronic antihypertensive therapy. The reduction tended to be more pronounced after 5-6 months of treatment than after 1 week (P = 0.06). During exercise, the plasma glycerol and nonesterified fatty acid concentrations were reduced. Plasma glucose concentration was reduced at the end of the exercise test during propranolol treatment only. Plasma lactate concentrations tended to be increased, but the difference was significant during pindolol treatment only. Oxygen uptake tended to decrease and respiratory exchange ratio to increase. Plasma potassium concentrations during exercise were significantly increased with all three beta-blockers. The effects on the metabolic variables during exercise were similar after 1 week and during long term (20/24 weeks) beta-blocker treatment. The study shows that submaximal endurance exercise capacity is impaired in patients with essential hypertension on beta-blocker therapy and that the impairment is maintained during long-term antihypertensive beta-blocker treatment. PMID- 2890592 TI - The pulsatile administration of luteinizing hormone-releasing hormone (LH-RH) for induction of ovulation. PMID- 2890593 TI - New approaches to the diagnosis and therapy of the luteinized unruptured follicle syndrome. AB - Ultrasound has been employed in diagnosing the luteinized unruptured follicle syndrome (LUF). Eighty-nine of 333 infertility patients were found to have LUF. The patients were divided into three groups. Group 1 was on no fertility medication. Twenty-five of 39 of this group released with HCG alone. Ten of the nonreleasers to HCG did release with HMG mixed with HCG. Group 2 patients had been treated with clomiphene and found to have LUF. Thirteen of 16 patients released with HCG and one of the failures released with HMG-HCG. Group 3 patients had been treated with HMG and had failed to release the ova despite HCG. Thirty one of 33 did release with HMG-HCG. Twenty-six of 89 patients achieved a pregnancy within six months of therapy and 20 of 36 patients with all fertility factors corrected achieved a pregnancy. PMID- 2890594 TI - Control of hyperprolactinemia with pergolide. AB - Ten patients with clinical, laboratory and radiographic evidence compatible with the diagnosis of prolactinoma were treated with two dopamine agonists. One group (N = 6) took bromocriptine and the other group (N = 4) used pergolide, a longer acting agent. Both medications were found to reduce prolactin levels significantly from baseline, but an oscillatory pattern with significant fluctuation was seen in the mean prolactin levels in the patients taking bromocriptine. Three patients did not achieve euprolactinemia on bromocriptine, 2.5 mg qid, the maximum dose used in this study. All of the study group taking pergolide became euprolactinemic rapidly; no more than a single dose of 100 micrograms/day was required. Tumor reduction was noted in two patients taking bromocriptine and two taking pergolide. The duration of side effects was shorter and compliance was improved on pergolide therapy. PMID- 2890595 TI - The contraceptive and hormonal requirements of the premenopausal woman: the years from forty to fifty. AB - There is a growing awareness that many women over 40 require both contraceptive protection and hormonal replacement for the symptoms of the climacteric. These women are still menstruating and the risk of pregnancy remains, overshadowed by the increased life-threatening risk due to childbirth in this age group. The risk of mortality due to the use of oral contraceptives is little increased for the nonsmoking woman in the over 40 years compared with the years under 40. In contrast, women over 40 who smoke are best advised not to use hormonal contraceptives. It is evident from all the existing data that combination therapy is strongly advised if any replacement therapy is to be given a woman. There is considerable evidence suggesting that estrogen alone may be insufficient therapy and progestogen should be added to prevent endometrial hyperplasia, decrease the risk of breast cancer and prevent bone loss. In the premenopausal woman, such therapy should also provide contraception. Many physicians allow women 35 to 45 who do not smoke to continue on an oral contraceptive if there is no contraindication. However, a minimum-dose product has yet to be found close to the ideal of fulfilling both the contraceptive and therapeutic needs of women traversing a physiologically very hazardous period. PMID- 2890596 TI - Carcinoembryonic antigen activity in human seminal plasma. AB - Carcinoembryonic antigen (CEA) immunoreactivity in the seminal plasma of 101 men was studied by enzyme immunoassay (EIA). It was found that (1) mean CEA (or CEA like activity) in seminal plasma is about 8.5 times higher than the upper CEA limit in normal serum; (2) there is no statistically significant difference between the antigen levels of normal controls and various groups of men with fertility problems, as well as between men with normal and those with abnormal spermiogram; (3) the prostate seems to be the main site of origin of CEA or CEA like activity in the seminal plasma. PMID- 2890597 TI - Comparison of corticosteroid therapy in the prevention of pelvic tissue reaction and adhesion formation. AB - The purpose of this research was to compare the effect of glucocorticoids administered in equivalent doses with respect to inflammatory response, fibrosis and adhesion formation. The animal model used was the Sprague-Dawley rat. The surgical technique involved incision and eversion of a portion of the proximal uterine horn. The glucocorticoids administered included methylprednisolone acetate (Medrol, The Upjohn Company), 6.25 mg/kg; hydrocortisone acetate (Hydrocortisone, Merck Sharp and Dohme), 25 mg/kg; betamethasone phosphate (Celestone Phosphate Injection, Schering Corp.), 1 mg/kg; and dexamethasone sodium phosphate (Hexadrol, Organon Pharmaceuticals), 1 mg/kg. These glucocorticoids were compared with a control solution of normal sodium chloride for injection (Abbott Laboratories), 0.5 mL/rat. Four weeks after the initial surgery, the uterine horns were histologically evaluated for inflammatory response, fibrosis and adhesion formation. Betamethasone phosphate produced a significant reduction (P less than 0.05) in fibrosis when compared with all other corticosteroid or control solutions. There was no statistically significant difference in the degree of inflammation or adhesion formation. PMID- 2890598 TI - Doppler sonography, contact scrotal thermography and venography: a comparative study in evaluation of subclinical varicocele. PMID- 2890599 TI - Morphological studies of human endometrium during continuous LH-RH agonist treatment. AB - Light and electron microscopic studies were performed on endometrial biopsies from seven healthy women after 2 to 17 months of daily intranasal luteinizing hormone-releasing hormone (LH-RH) agonist treatment for contraceptive purposes. Hormone analyses revealed inhibition of ovulation in all the women. Light microscopy showed an inactive or weak proliferative endometrial pattern, with no signs of hyperplasia. Ultrastructurally, the epithelial and stromal cells of the endometrium displayed signs of low metabolic activity. Since the results are contradictory to those earlier presented by others, further studies are necessary to exclude the potential risk of hyperestrogenic stimulation of the endometrium during continuous LH-RH agonist treatment. PMID- 2890600 TI - Changes in reproductive behavior and urinary pheromone induction in rats through beta-adrenergic stimulation. AB - Treating rats in proestro with beta-adrenergic stimulants (epinephrine and phenotherol bromhydrate) significantly increases the instances of fertile coitus. Concurrently, it induces the excretion through the urine of compounds with pheromonal action that affect males and females of the same strain, increasing their reproductive activity. PMID- 2890601 TI - Conformational features of dynorphin A-(1-13), Laser Raman spectroscopic studies. AB - Conformational features of dynorphin A-(1-13) were examined by laser Raman spectroscopy. Dynorphin A-(1-13) appears to have a mixture of extended beta pleated sheet and "random" structure. PMID- 2890602 TI - Endocrine and metabolic changes in response to the peroral administration of beta adrenergic agonists in calves. PMID- 2890603 TI - The use of psychotropic drugs in a family practice in a community of low socio economic status. PMID- 2890604 TI - Role of conventional management and alternative therapies in limiting infarct size in acute myocardial infarction. PMID- 2890605 TI - HLA-DR and -DQ DNA polymorphisms: new linkage relationships established by RFLP genomic typing in Polynesians and Melanesians. AB - Class II restriction fragment length polymorphisms (RFLPs) of DR beta, DQ beta, and DQ alpha loci were examined in Polynesians of the southwest Pacific and in non-Austronesian-speaking Melanesians from the Papua New Guinean Highlands. Polynesians, previously considered to have a restricted set of HLA-DR antigens, showed class II gene heterogeneity associated with DR2, DR5, DRw6, and DRw8 RFLPs. Furthermore, Melanesians and Polynesians share certain antigens such as DRw6 and DRw8, but the DR beta 2 genes associated with DRw6 and the DQ genes associated with DRw8 are population-specific and show little or no overlap. This study has shown that genetic analysis of closely linked polymorphic genes is a powerful anthropological tool and supports the view that Polynesians represent an independent colonizing group in the Pacific, rather than a group evolved from within Melanesia. PMID- 2890606 TI - T-cell receptor alpha chain V region polymorphism linked to primary autoimmune hypothyroidism but not Graves' disease. AB - T-cell receptor alpha- and beta-chain polymorphisms have been investigated in patients with autoimmune thyroid disease. Using a cDNA probe for the T-cell receptor alpha chain, a 1.4-kb V alpha Taq I restriction fragment was found in 25 of 33 patients with autoimmune hypothyroidism compared to 33 of 61 control subjects (p less than 0.05) and 16 of 43 patients with Graves' disease (p less than 0.001 compared to patients with autoimmune hypothyroidism). Moreover, when Graves' patients were divided according to HLA-DR3 status, there was a significantly reduced frequency of the 1.4-kb V alpha fragment in HLA-DR3 negative patients (p less than 0.05 compared to controls). There was no significant association of either thyroid disorder with polymorphisms of the T cell receptor alpha- or beta-chain-constant region genes, after Taq I and Bgl II digestion, respectively. These results show that inherited variation in T-cell receptor genes, recognizable before any somatic event has taken place, may play a role in susceptibility to autoimmune disease. PMID- 2890608 TI - How to get ahead in medicine: "Invent a pessary". PMID- 2890607 TI - HLA-DR-DQ haplotypes defined by restriction fragment analysis. Correlation to serology. AB - Through the analysis of RFLP (restriction fragment length polymorphism) of the HLA-DR beta, -DQ alpha, and -DQ beta genes from 70 serologically well characterized individuals, we have established unique HLA-DR-DQ RFLP haplotypes correlating to all of the DR1-w14 specificities. The RFLP of DR beta, DQ alpha, and DQ beta genes is very high using the restriction enzyme TaqI and 21 DR-DQ RFLP haplotypes were defined with this restriction enzyme. Our analysis confirms the strong linkage disequilibrium between alleles in the DR and DQ loci. DR beta RFLP indicates a common ancestor for the DR alleles within either of the supertypic DRw52 and DRw53 specificities. The DQ beta gene shows a high degree of RFLP, and the RFLP alleles partly reflect the serologic DQw1-w3 specificities. The results presented here also demonstrate the heterogeneity of DRw6 (DRw13 and DRw14) associated haplotypes, and the DRw13 related Dw18 and Dw19 specificities were found to have distinct DR-DQ haplotypes. The DQw1 positive haplotypes DR1, 2, w10, w13, and w14 are related with regard to DQ alpha and DQ beta RFLPs and the DRw52 positive haplotypes DR3, w11, and w12, as well as the DRw53 positive haplotypes DR4, 7, and w9, are related with regard to DR beta and DQ alpha RFLPs. These findings indicate that polymorphic sequences around the DQ alpha gene are associated with DR beta and DQ beta polymorphism, which suggests a location of the DQ alpha gene between DR beta and DQ beta. PMID- 2890609 TI - Evaluating capitation payments. What are your odds? PMID- 2890610 TI - Infected intrapulmonary bronchial cyst. PMID- 2890611 TI - ISMS organization. PMID- 2890612 TI - Illinois state government. PMID- 2890613 TI - A unique T-cell line derived from an HTLV-1-negative adult T-cell leukemia patient. AB - A unique T-cell line, designated ATL-5T, was established from lymphoma cells in pericardial effusion of an adult T-cell leukemia (ATL) patient not carrying HTLV 1 provirus. The cell line is OKT4 and/or Leu3a+ and OKT8 and/or Leu2a+, but interleukin 2 receptor (IL2R)- and HTLV-1 provirus genome negative, and has cytogenetically abnormal karyotypes. The cell line contains rearranged T-cell receptor beta-chain gene, which was identical in rearrangement pattern to the T cell receptor beta-chain gene in primary cells. These results suggest that factors other than HTLV-1 may sometimes be associated with HTLV-1-negative ATL. The ATL-5T cell line we describe here is unique, and should contribute to further elucidation of the mechanisms involved in the pathogenesis of HTLV-1-negative ATL and HTLV-1-positive ATL. PMID- 2890614 TI - Aberrant expression of ganglioside and asialoglycosphingolipid antigens in adult T-cell leukemia cells. AB - Gangliosides (GM3, GD3, GM2, gangliotetraose-series gangliosides) and their asialo derivatives of several adult T-cell leukemia (ATL) cell lines (ATL-1K, ATL 3I, ATL-5S, and MT-2 cells) and the lymphocytes from a patient with ATL were quantified by highly sensitive enzyme-immunostaining on silica gel thin layer chromatograms using specific antiglycolipid antibodies. GM2 and GD3 gangliosides and asialo GM1 (GA1) newly appeared in all cultured ATL cells and the lymphocytes from patients with ATL but not in normal human T-lymphocyte-rich fraction. Gangliotetraose-series gangliosides, GM1a, GD1a and GD1b, were also found in cultured ATL cells, but were not detected in normal human lymphocytes or the lymphocytes of a patient with ATL. Quantitative immunostaining analysis of GM2, GD3 gangliosides and GA1 in T-cell lines from non ATL leukemia (Molt-3, CEM and Jurkat) revealed GM2 gangliosides in all the T-cells from non ATL tested and GA1 in Jurkat cells, but no GD3 ganglioside was found in the non ATL leukemia cells tested. The above results indicate that ganglioside GD3 may be a T-cell glycosphingolipid antigen associated with ATL, and ganglioside GM2 and GA1 may be useful as surface markers related with ATL, as well as T-cell lymphoma. The contents of GA1, GM3, GD3, GM2 and gangliotetraose-series gangliosides in ATL cells were all different, even though all the cells used have a common antigen reactive with monoclonal OKT-4 antibody, indicating that there are several subsets of human inducer/helper T-cells, which possess different metabolism and expression of gangliosides. PMID- 2890615 TI - Potent inhibitory effect of antibiotic 1233A on cholesterol biosynthesis which specifically blocks 3-hydroxy-3-methylglutaryl coenzyme A synthase. PMID- 2890616 TI - Tyrosine hydroxylase immunoreactivity identifies possible catecholaminergic fibers in the organ of Corti. AB - Antibodies to tyrosine hydroxylase, dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase were used in an immunocytochemical examination of catecholamines in the cochlea. In cryostat sections, tyrosine hydroxylase and dopamine beta-hydroxylase-like immunoreactivities fibers were seen in the modiolus that did not extend to the organ of Corti. These corresponded to blood vessel-associated and non-blood vessel-associated fibers that have been previously described with histofluorescence. In surface preparations, tyrosine hydroxylase-like immunoreactivity was seen in the organ of Corti, in the inner and tunnel spiral bundles, suggesting an efferent component may be catecholaminergic. PMID- 2890617 TI - Coexistence of putative neuroactive substances in lateral olivocochlear neurons of rat and guinea pig. AB - We have used the retrograde axonal transport of Fast Blue, injected intra cochlearly, to identify in the rat lateral superior olive (LSO) neurons which belong to the lateral olivocochlear system (LOCS). Using immunohistofluorescence technique, we have localized within Fast Blue-labeled neurons immunostainings for enkephalins (Met-enkephalin, Met-enkephalin-Arg6-Gly7-Leu8), dynorphins (alpha neo-endorphin, dynorphin 1-17) or choline acetyltransferase (ChAT). Many Fast Blue-labeled neurons did not show any immunostaining, but all the immunostained neurons found in the LSO were Fast Blue-labeled. In immunohistofluorescence colocalization experiments of two antigens, we could colocalize within the same neurons of the rat LSO immunostainings for ChAT and enkephalins and for ChAT and dynorphins. In each case, neurons only immunostained for ChAT, enkephalins or dynorphins could also be observed. A colocalization of the immunostainings for Met-enkephalin and dynorphins within neurons of the guinea pig and rat LSO was also found. However, in this case, neurons which did not show colocalization were only Met-enkephalin-immunoreactive, thus suggesting that all the dynorphins immunoreactive LSO neurons also contain enkephalins. These findings support the idea that the neurons of the LSO which contain ChAT-, enkephalin- or dynorphin immunostainings project to the cochlea and belong to the LOCS. It can also be concluded that acetylcholine, enkephalins and dynorphins coexist within a same population of neurons of the LOCS, although other patterns of co-containment of neuroactive substances within LOCS neurons may also exist. PMID- 2890619 TI - Cellular transglutaminase has affinity for extracellular matrix. AB - Cellular transglutaminase (TGase) was demonstrated as an intracellular enzyme by immunofluorescence in WI-38 cells. Following cell membrane perturbation by Triton X-100 treatment, TGase was bound to the extracellular matrix and was found to coexist with fibronectin as visualized by immunofluorescence microscopy. The binding of TGase to the cell matrix was blocked by anti-fibronectin antibody. Exogenous sources of soluble TGase were transferred to the extracellular matrix of an untreated or methanol fixed cell. The experimental data indicated that "particulate bound" TGase is a consequence of soluble TGase binding to the extracellular matrix following cell rupture. PMID- 2890618 TI - Culture of mouse brain capillary endothelial cell lines that express factor VIII, gamma-glutamyl transpeptidase, and form junctional complexes in vitro. AB - The isolation and culture of cell lines from mouse brain capillary endothelium (MBE) is described. Cells migrating from collagenase-treated capillary fragments proliferated rapidly in the 1st wk of culture forming large epithelioid cobblestonelike colonies. The cells showed only marginal proliferation after 2 to 3 wk in culture, until peripheral cells migrated away from the colony which exhibited a marked degree of proliferation. These cells were trypsinized and subcultured to confluence. The cells can be maintained for well over 40 passages and seem to retain their endothelial morphology. The endothelial origin of these cells was demonstrated by positive immunoperoxidase reactivity with Factor VIII related antigen, specific binding of Bandeiraea simplicifolia lectin and gamma glutamyl transpeptidase activity. Electron microscopic examination of the MBE cells showed junctional complexes including intermediate junctions, but no tight junctions. The overall ultrastructure indicates that a degree of dedifferentiation has occurred, the cells ultrastructurally resembling immature endothelium. An earlier investigation of cultured mouse brain endothelial cells reported a cell line that had lost many functional and structural characteristics. Our study demonstrates, as the previous one, that a certain degree of dedifferentiation needs to occur if MBE cells are to be maintained for long-term culture. However, the degree of dedifferentiation seems to be variable, depending in part on the culture conditions employed. PMID- 2890620 TI - Autolytic system of Staphylococcus simulans 22: influence of cationic peptides on activity of N-acetylmuramoyl-L-alanine amidase. AB - Pep 5 and nisin are cationic peptide antibiotics which in addition to their membrane-disruptive action induce autolysis in staphylococci. To investigate the mechanism of lysis induction, the influence of the peptides on the activity of the N-acetylmuramoyl-L-alanine amidase of Staphylococcus simulans 22 was studied. In experiments with isolated cell walls at low ionic strength, the amidase activity was stimulated by the addition of Pep 5 and nisin, as well as by polylysine, streptomycin, and mono- and divalent cations. The concentrations necessary for activation depended on the nature of the cation and ranged from 5 microM for poly-L-lysine (n = 17) to 150 mM for Na+ at a cell wall concentration of 100 micrograms of cell walls per ml. No effect was observed if the cell walls were devoid of polyanionic constituents. Kinetic data suggested that the amidase bound to the teichoic and teichuronic acids of the cell wall and was thereby inhibited. Cationic molecules reversed this inhibition, most likely by displacing the enzyme from the polyanions. If the concentrations of the larger peptides were high in relation to cell wall concentration, the activation turned into inhibition, presumably by interfering with the access of the enzyme to its substrate. These experiments demonstrate that the activity of the amidase is modulated by basic peptides in vitro and help to explain how Pep 5 and nisin may cause lysis of treated cells. PMID- 2890621 TI - Relationship between two major immunoreactive forms of arginase in Neurospora crassa. AB - Two major immunoreactive proteins of Mr 41,700 and 36,100 have been detected in crude mycelial extracts with polyclonal antibodies raised against arginase purified from Neurospora crassa. The latter corresponded to the protein used to obtain the antibodies. Both polypeptides were either missing or present in very low amounts in mutant strains having little or no detectable arginase activity. The relative proportion of the two species was altered in strains containing the nitrogen catabolite regulatory mutation nit-2. Peptide mapping indicated that the two species are very closely related, but several of the peptides which appeared to be identical by staining reacted differently with the antibodies. Both species were produced by in vitro translation of poly(A)+ mRNA, although the larger species was produced to a much smaller extent than was expected from its abundance in vivo. The results suggest the existence of multiple forms of arginase in N. crassa which differ in their response to nitrogen catabolite regulation. PMID- 2890622 TI - Identification of two ancillary subunits of Escherichia coli type 1 fimbriae by using antibodies against synthetic oligopeptides of fim gene products. AB - We have chemically synthesized oligopeptides corresponding to the NH2-terminal stretch of two gene products, designated FimG and FimH, of the fim gene cluster of Escherichia coli. These synthetic peptides, designated S-T1FimG(1-16) and S T1FimH(1-25)C, evoked antibodies in rabbits that reacted with 14- and 29 kilodalton subunits, respectively, of dissociated fimbriae encoded by the recombinant plasmid pSH2 carrying the genetic information for the synthesis and expression of functional type 1 fimbriae. Neither of these fimbrial proteins was detected in dissociated fimbrial preparations from nonadhesive E. coli cells carrying the mutant plasmid pUT2002, containing a restriction site-specific deletion of fimG and fimH. Anti-S-T1FimH(1-25)C inhibited the adherence of type 1 fimbriated E. coli to epithelial cells. Immunoelectron microscopy revealed that anti-S-T1FimH(1-25)C, but not anti-S-T1FimG(1-16), bound to intact type 1 fimbriae of E. coli at the fimbrial tips and at long intervals along the fimbrial filaments. Anti-S-T1FimG(1-16) appeared to be directed at epitopes not accessible on the intact fimbriae and consequently failed to bind to intact fimbriae or to block fimbrial attachment. Our results suggest that the fimG and fimH gene products are components of type 1 fimbriae and that FimH may be the tip adhesin mediating the binding of type 1 fimbriated E. coli to D-mannose residues on mucosal surfaces. PMID- 2890623 TI - Cloning of genes that suppress an Escherichia coli K-12 alanine auxotroph when present in multicopy plasmids. AB - To facilitate molecular analyses of a previously uncharacterized gene involved in alanine synthesis, attempts were made to clone the wild-type allele of this gene, alaA, with a mini-Mu plasmid element used for in vivo cloning. Seventy-six independent Ala+ plasmids were isolated and characterized. Physiological, enzymological, and restriction endonuclease analyses indicated that three different genes, none of them alaA, were cloned. These genes were avtA+, which encodes the alanine-valine transaminase (transaminase C); tyrB+, which encodes the tyrosine-repressible transaminase (transaminase D); and a previously undescribed gene, called alaB, which encodes an alanine-glutamate transaminase. PMID- 2890624 TI - Nucleotide sequences of the genes encoding type 1 fimbrial subunits of Klebsiella pneumoniae and Salmonella typhimurium. AB - The nucleotide sequences of the genes encoding the subunits of Klebsiella pneumoniae and Salmonella typhimurium type 1 fimbriae were determined. Comparison of the predicted amino acid sequences of the two subunits revealed domains in which the sequences were highly conserved. Both gene products possessed signal peptides, a fact consistent with the transport of the fimbrial subunit across the membrane, but these regions showed no amino acid homology between the two proteins. The predicted N-terminal amino acid sequences of the processed fimbrial subunits were in good agreement with those obtained by purification of the fimbrial subunits. PMID- 2890626 TI - Two cases of benzodiazepine toxicity in children. AB - While benzodiazepines have been widely used in adult populations, their role in the treatment of anxiety disorders in children and adolescents has not been well established. The authors report on two cases in which benzodiazepine use resulted in psychotic symptoms. The importance of eliciting a careful history as well as being familiar with drugs' side effects and withdrawal effects is stressed. PMID- 2890627 TI - Autologous transplantation with circulating hemopoietic stem cells. AB - Circulating stem cells exist in sufficient numbers in mouse, dog, and man to allow collection and transplantation after ablative treatment. Preclinical studies in the mouse have shown a low concentration, with a transplantation potential ratio of bone marrow to blood of 1:100. The ratio of circulating stem cells to bone marrow stem cells is more favorable in the dog (1:10-20). Recent pilot studies carried out in different centers with 10 patients have shown that this approach is feasible in man, too. It appears that 5 X 10(8) mononuclear cells/kg of body weight collected by seven or eight leukapheresis procedures of about 4 hrs each is sufficient for fast hemopoietic recovery after marrow ablative treatment. Potential advantages of the use of blood stem cells over bone marrow stem cells are the decreased likelihood of contamination with malignant cells, the avoidance of general anesthesia, and the infusion of immunocompetent cells, which might hasten immunorecovery in the autologous setting. PMID- 2890625 TI - Mechanism of attachment of swarm cells of Thiothrix nivea. AB - Swarm cells of Thiothrix nivea were found to possess a group of fimbriae at one pole. The other pole either was bare or possessed from one to three fimbriae. By using this polarity as a marker, it was found that the initial step in attachment of swarm cells involves the fimbriated pole and that this initial step is followed by the production of holdfast material. PMID- 2890628 TI - Vitamin K-dependent carboxylase. Control of enzyme activity by the "propeptide" region of factor X. AB - A liver microsomal enzyme catalyzes the vitamin K-dependent posttranslational carboxylation of specific glutamyl residues of a limited number of plasma proteins to gamma-carboxyglutamyl residues. The intracellular precursor forms of these proteins are known to contain a homologous basic amino acid-rich propeptide region between the signal peptide region and the amino terminus of the mature protein. This region of the precursor protein has been implicated as a possible recognition site for the carboxylase enzyme. A 20-residue peptide containing the octadecapropeptide of human clotting factor X has now been shown to strongly stimulate the activity of the enzyme toward a noncovalently linked substrate. This stimulatory effect is seen at less than micromolar concentrations and is accompanied by a decrease in the Km of the glutamic acid substrate. These observations raise the possibility that the catalytic activity of other enzymes involved in protein processing may be regulated by a portion of their normal substrates. PMID- 2890629 TI - Structure of the peptide network of pneumococcal peptidoglycan. AB - The peptide network of Streptococcus pneumoniae cell walls was solubilized using the pneumococcal autolytic amidase (N-acetylmuramoyl-L-alanine amidase, EC 3.5.1.28). The peptide material was fractionated into size classes by gel filtration followed by reverse-phase high-performance liquid chromatography which resolved the peptide population into over 40 fractions. About 40% of the lysines present participate in cross-links between stem peptides. The main components (3 monomers, 5 dimers, and 2 trimers), accounting for 77% of all the wall peptides, were purified. Their structures were determined using a combination of amino acid and end-group analysis, mass spectrometry, and gas-phase sequencing. Two different types of cross-links between stem peptides were found. In the most abundant type there is an alanylserine cross-bridge between the alanine in position 4 of the donor stem peptide and the lysine at position 3 of the acceptor peptide, as in type A3 peptidoglycan. In the second type of cross-link there is no intervening cross-bridge, as in the type A1 peptidoglycan of Gram-negative bacteria. The data indicate that pneumococcal peptidoglycan has a structural complexity comparable to that recently shown in some Gram-negative species. PMID- 2890630 TI - The role of protein structure in the mitochondrial import pathway. Analysis of the soluble F1-ATPase beta-subunit precursor. AB - A series of proteins containing defined internal and presequence deletions in the F1-ATPase beta-subunit precursor have been synthesized in vitro using a linked transcription-translation system. These different forms of the protein have been analyzed by the combination of gel filtration and in vitro mitochondrial import studies. These studies reveal that the soluble F1 beta-subunit precursor (55 kDa) forms a homooligomeric assembly of apparent molecular weight 230,000 on gel filtration analysis. The formation of this tetrameric beta-protein was dependent on the sequence between residues 122 and 144 of the precursor and was independent of the presence of a mitochondrial presequence within the first 19 residues of the precursor. When the tetrameric F1 beta-precursor was partially purified from the translation reaction it was incompetent for import into mitochondria. However, import of the partially purified beta-subunit could be restored by addition of reticulocyte lysate protein. In the absence of the tetramer-forming sequence, the protein behaved as an aggregate complex approximately 400 kDa in size. Formation of the high molecular weight aggregate and import into mitochondria was dependent upon a functional presequence at the amino terminus of the precursor. These studies are discussed in terms of the maintenance of an import competent structure for mitochondrial precursors and role of soluble factors in this process. PMID- 2890631 TI - Receptor-mediated phosphorylation of spermatozoan proteins. AB - These studies are the first to report egg peptide-mediated stimulation of protein phosphorylation in spermatozoa. Speract (Gly-Phe-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly) or resact (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg-Leu-NH2) stimulated the incorporation of 32P into various proteins of isolated spermatozoan membranes in the presence, but not absence, of GTP. The Mr of three of the phosphorylated proteins were 52,000, 75,000, and 100,000. GTP gamma S (guanosine 5'-O-(3-thiotriphosphate] but not GDP beta S (guanosine 5'-O-(2 thiodiphosphate] or GMP-PNP (guanylyl imidodiphosphate) also supported the peptide-mediated stimulation of protein phosphorylation. The peptides markedly stimulated guanylate cyclase activity, and GTP gamma S or GTP but not GMP-PNP served as effective substrates for the enzyme. The accumulation of cyclic AMP was not stimulated by the peptides. Subsequently, it was shown that added cyclic GMP or cyclic AMP increased 32P incorporation into the same membrane proteins as those observed in the presence of peptide and GTP. The amount of cyclic GMP (up to 3 microM) formed by membranes in the presence of peptide and 100 microM GTP equated with the amount of added cyclic GMP required to increase the 32P content of a Mr 75,000 protein selected for further study. 32P-Peptide maps of the Mr 75,000 protein indicated that the same domains were phosphorylated in response to cyclic nucleotides or to egg peptide and GTP. Intact cells were subsequently incubated with 32P to determine if the radiolabeled proteins observed in isolated membranes also would be obtained in intact cells. The 32P contents of proteins of Mr 52,000, 75,000, and 100,000 were significantly increased by the addition of resact. Peptide maps confirmed that the increased 32P incorporation obtained in a Mr 75,000 protein of isolated membranes occurred on the same protein domains as the 32P found on the Mr 75,000 protein of intact cells. These results suggest that a GTP or GTP gamma S requirement for peptide-mediated protein phosphorylation in spermatozoan membranes is mainly due to the enhanced formation of cyclic GMP, and it therefore is likely that peptide-induced elevations of cyclic nucleotide concentrations in spermatozoa are responsible for the specific increases in 32P associated with at least three sperm proteins, all apparently localized on the plasma membrane. PMID- 2890632 TI - Cross-linking study of the quaternary fine structure of mitochondrial F1-ATPase. AB - A method has been developed for exploring the quaternary fine structure of oligomeric proteins by crosslinking studies and applied to bovine heart mitochondrial F1-ATPase. The F1 was first labeled with 1-fluoro-2,4-dinitro [14C]benzene, subsequently reduced with sodium hydrosulfite, and finally cross linked with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. Gel electrophoresis in the chemically modified protein in the presence of sodium dodecyl sulfate and mercaptoethanol showed the existence of a 105-115-kilodalton molecular species in addition to the five monomeric subunits of F1. This cross-linked species could be alpha 2, alpha beta, or beta 2. Isolation of the cross-linked species and titration with 5,5'-dithiobis-(2-nitrobenzoic acid) showed the absence of sulfhydryl group. Therefore, the cross-linked species must be the dimer beta 2. After digestion of the purified beta 2 with pepsin, a single radioactive peptide was isolated. Determination of the amino acid sequence of this peptide and comparison of its radioactivity with the total radioactivity on beta-subunits show that it was formed exclusively by cross-linking Lys162 of one beta-subunit with Glu199 of another beta-subunit. The observation that two beta-subunits can be cross-linked by a rigid phenylenediamine bridge of 5.7- or 4.3-A length is difficult to reconcile with the widely assumed structure of F1 with the alpha- and beta-subunits occupying alternate corners of a planar hexagon, but is consistent with the structure in which a triangular set of three beta-subunits sits above a triangular set of three alpha-subunits in a staggered conformation. PMID- 2890634 TI - Immunoaffinity purification and characterization of vacuolar H+ATPase from bovine kidney. AB - Vacuolar proton-translocating ATPase from bovine kidney was purified in one step by immunoprecipitation and immunoaffinity chromatography using an immobilized anti-H+ATPase monoclonal antibody. The monoclonal antibody affinity matrix coprecipitated polypeptides with Mr of 70,000, a cluster at 56,000, 45,000, 42,000, 38,000, 33,000, 31,000, 15,000, 14,000, and 12,000 from solubilized bovine kidney microsomal membranes, a pattern that was unaffected by different detergent washing conditions. A nearly identical pattern of polypeptides was observed in H+ATPase partially purified by an entirely independent method. The immunoaffinity purified H+ATPase had reconstitutively active ATP-induced acidification and potential generation that was inhibited by N-ethylamaleimide. The purified enzyme had specific activities as high as 3.1 mumol/min/mg protein, dual pH optima at 6.5 and 7.2, and a Km for ATP of 150 microM. The substrate preference was ATP greater than ITP much greater than UTP greater than GTP greater than CTP. The affinity purified H+ATPase was stimulated by phosphatidyl glycerol greater than phosphatidyl inositol much greater than phosphatidyl choline greater than phosphatidyl serine. The immunoaffinity purified enzyme did not require monovalent anions or cations for activity, and the divalent cation preference for activity was Mn, Mg much greater than Ca greater than Co much greater than Sr, Ba. The enzyme was not inhibited by ouabain, azide, or vanadate, but had kappa 1/2 inhibitory concentrations of 22.2 microM for N-ethylmaleimide, 14.9 microM for NBD-Cl, 4.9 microM for N,N'-dicyclohexylcarbodiimide, 13.8 microM for 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, and 315 microM for Zn, values close to those for inhibition of proton transport in the native vesicles. The affinity purified kidney enzyme has similarities to but also significant differences in structural and enzymatic properties from those reported for other vacuolar H+ATPase. PMID- 2890635 TI - Structure of a human serum amyloid A gene and modulation of its expression in transfected L cells. AB - The structure of a human serum amyloid A (SAA) genomic clone (SAAg9) has been analyzed and the nucleotide sequence of the coding regions is compared with that of the cDNA for apoSAA1. The leader and coding sequences of exons 2 and 3 are identical to SAA1. However, there are 10 nucleotide and 7 derived amino acid substitutions in exon 4. These changes are identical to the amino acid sequence of the amyloid protein associated with familial Mediterranean fever. In particular, the amino acid substitution (Thr to Phe) at residue 69 of SAA1 may have an important role in this type of hereditary amyloidosis. The genomic clone SAAg9 has been transfected into mouse L cells, and constitutive expression of human specific mRNA and protein were observed in stable transfected clones. The expression of both SAA mRNA and protein were increased by incubation of the transfected cells with purified human interleukin-1 (IL-1), both human and mouse recombinant IL-1, and recombinant human tumor necrosis factor alpha. The induction of SAA is pretranslational and is likely to be mediated by protein factor(s) since incubation with cycloheximide diminished IL-1-dependent increase in SAA mRNA. PMID- 2890633 TI - Production and characterization of a monoclonal antibody to vacuolar H+ATPase of renal epithelia. AB - A monoclonal antibody to vacuolar H+ATPase isolated from bovine kidney medulla was produced and characterized by immunoprecipitation and immunocytochemistry. The antibody, immobilized on beads, specifically immunoprecipitated both solubilized N-ethylmaleimide-sensitive ATPase activity and proton-transporting vesicles from renal microsomes; control experiments with an "irrelevant" monoclonal antibody showed no immunoprecipitated activity. By fluorescent immunocytochemistry, the antibody stained the membranes of intracellular vacuolar compartments in LLC-PK1 cells. Immunocytochemical staining showed that the monoclonal antibody colocalized partially with N-(3-[2,4 dinitrophenyl)amino)propyl)-N-(3-amino-propyl)methylamine, a probe for acidic compartments, with the endocytic markers dextran and transferrin, with the lysosomal probe alpha 2-macroglobulin, and with clathrin. The anti-vacuolar H+ATPase antibody showed no colocalization with staining for mitochondrial H+ATPase. The anti-vacuolar H+ATPase antibody should serve as a specific probe for examining the distribution and dynamics of the vacuolar proton pump in renal epithelial cells. PMID- 2890637 TI - Mutations that uncouple the beta-adrenergic receptor from Gs and increase agonist affinity. AB - The deletion of residues 239-272 from the hamster beta-adrenergic receptor resulted in a loss of the ability of the receptor, expressed in mouse L cells, to stimulate adenylate cyclase (Dixon, R. A. F., Sigal, I. S., Rands, E., Register, R. B., Candelore, M. R., Blake, A. D., and Strader, C. D. (1987) Nature 326, 73 77). This mutant receptor (D(239-272)beta AR) bound the agonist isoproterenol with a single class of binding sites, in contrast to the wild-type beta adrenergic receptor, which exhibited two classes of agonist affinity sites. We now report that the affinity of D(239-272)beta AR for isoproterenol is relatively insensitive to detergent solubilization or to treatment with either GTP or NaF, indicating the absence of a receptor-Gs interaction. Whereas deletions within the region of amino acids 229-258 did not reduce the ability of the receptor to couple to Gs or to stimulate adenylate cyclase, the deletion of either of the regions 222-229 or 258-270 resulted in receptors which were unable to couple to Gs. The affinities of D(222-229)beta AR, D(239-272)beta AR, and D(258-270)beta AR toward isoproterenol were greater than that observed for the low affinity, uncoupled form of the wild-type receptor. These results suggest a role for the regions of the beta-adrenergic receptor encompassing amino acids 222-229 and 258 270, which are predicted to form amphiphilic helices, in the agonist-promoted activation of Gs. PMID- 2890636 TI - The major metabolite of doxorubicin is a potent inhibitor of membrane-associated ion pumps. A correlative study of cardiac muscle with isolated membrane fractions. AB - Doxorubicin (adriamycin) is a highly effective cancer chemotherapeutic drug but its clinical utility is limited by its cardiotoxicity. Doxorubicinol, the major metabolite of doxorubicin, is up to 10 times more potent than doxorubicin at inhibiting isometric contraction of the papillary muscle isolated from the right ventricle of rabbit heart. Doxorubicinol also increases resting tension of isolated cardiac muscle indicative of incomplete relaxation between contractions, a characteristic of doxorubicinol but not of doxorubicin. This study assesses the effect(s) of doxorubicinol on a variety of ion pumps which may explain, in part, the action of the metabolite in the intact muscle. We find the doxorubicinol is a potent inhibitor (IC50 less than 5 micrograms/ml) of calcium-stimulated ATPase activity of sarcoplasmic reticulum from canine heart and rabbit skeletal muscle. At comparable levels, doxorubicinol is also a potent inhibitor of (Na + K)-ATPase of cardiac sarcolemma and the Mg-dependent ATPase activity referable to the F0F1 proton pump of mitochondria. For each of these ion pumps, doxorubicinol is at least 80 times more potent an inhibitor than doxorubicin. Doxorubicinol, between 10 and 50 micrograms/ml, increases resting tension up to 4-fold in isolated papillary muscles cyclically contracting at 30 times/min. Resting stress is relatively insensitive to doxorubicin. Thus, doxorubicinol is a potent inhibitor of several key cationic pumps that directly or indirectly regulate cell calcium and inhibits relaxation in the isolated fiber preparation. These observations add a new dimension to understanding the cardiotoxicity of doxorubicin. PMID- 2890638 TI - Activation of rat caudate tyrosine hydroxylase phosphatase by tetrahydropterins. AB - Tyrosine hydroxylase phosphatase activity in rat caudate nucleus was separated into three peaks by chromatography on DEAE-cellulose. [32P]Tyrosine hydroxylase phosphorylated by cyclic AMP-dependent protein kinase was dephosphorylated only by the major peak eluting at 0.3 M NaCl, while tyrosine hydroxylase phosphorylated by Ca2+-calmodulin-dependent protein kinase was also dephosphorylated by two calcium-inhibited phosphatases. The Vmax of the enzyme in the major DEAE peak was increased by 10 microM tetrahydrobiopterin (BH4) from 0.78 to 5.0 fmol min-1 mg-1 while the Km was only slightly affected, increasing from 45 to 62 pM. The activation could not be reversed by dilution. On Sephadex G 200, the enzyme was found to consist of two major forms with molecular masses of 420 and 100 kDa. In contrast to the activation of liver phosphatases by freezing with beta-mercaptoethanol, activation by tetrahydrobiopterin was not associated with a shift in the molecular weight of the phosphatase to lower molecular weight forms. Other reduced pterins, including tetrahydroneopterin, 6 methyltetrahydropterin, and 5-methyltetrahydrofolate, also activated the enzyme, while oxidized pterins had no effect. GTP, the metabolic precursor of tetrahydrobiopterin, was a potent inhibitor of the phosphatase reaction, inhibiting by 65% at a concentration of 1 microM. These findings suggest a close regulatory interrelationship between the tetrahydrobiopterin synthetic pathway and catecholamine biosynthesis. PMID- 2890639 TI - The hydrophobic tryptic core of the beta-adrenergic receptor retains Gs regulatory activity in response to agonists and thiols. AB - The function of structural domains of the beta-adrenergic receptor were probed by studying the ability of tryptic fragments of the receptor to catalyze the binding of guanosine-5'-O-(3-thiotriphosphate (GTP gamma S) to the GTP-binding regulatory protein, Gs. beta-Adrenergic receptor purified from turkey erythrocytes was treated with trypsin under nondenaturing conditions. Such treatment decreased beta-adrenergic ligand binding activity by only 15-25%. Active components of the limit digest were repurified by affinity chromatography on alprenolol-agarose and then reconstituted with purified Gs into unilamellar phospholipid vesicles. After reconstitution, the proteolyzed receptor was able to catalyze agonist-stimulated binding of GTP gamma S to Gs at a rate and extent equivalent to that of the nonproteolyzed receptor. The proteolyzed receptor was also partially activated upon reduction by dithiothreitol, as previously reported for the intact receptor (Pedersen, S.E., and Ross, E.M. (1985) J. Biol. Chem. 260, 14150-14157). The repurified, active tryptic digest contained two detectable peptides. One, of approximately 2 X 10(4) Da, contained either four or five of the amino-terminal membrane-spanning domains plus the intervening hydrophilic loops but not the amino-terminal extracellular, glycosylated peptide. The second, of 9,000-10,000 Da, was composed essentially of the two carboxyl-terminal membrane-spanning domains and the intervening extracellular, hydrophilic loop. These data indicate that most of the large intracellular hydrophilic loop and the hydrophilic, carboxyl-terminal region of the receptor are not necessary for the agonist stimulated regulation of Gs. PMID- 2890640 TI - Inactivation of gamma-glutamylcysteine synthetase, but not of glutamine synthetase, by S-sulfocysteine and S-sulfohomocysteine. AB - The reactions catalyzed by gamma-glutamylcysteine synthetase and glutamine synthetase are thought to proceed via enzyme-bound gamma-glutamyl phosphate intermediates. We investigated the possibility that S-sulfocysteine and S sulfohomocysteine might act as analogs of gamma-glutamyl phosphate or of the associated putative tetrahedral intermediates. The D- and L-enantiomers of S sulfocysteine and S-sulfohomocysteine were found to rapidly inactivate rat kidney gamma-glutamylcysteine synthetase but to be reversible inhibitors of sheep brain glutamine synthetase. Inactivation of gamma-glutamylcysteine synthetase does not require ATP and is associated with noncovalent binding of close to 1 mol of inactivator/mol of enzyme. The findings indicate that the S-sulfo amino acids are transition-state analogs, and that binding of S-sulfo amino acid to the enzyme induces formation of a very stable enzyme-inactivator complex. The data suggest that stabilization of the enzyme-inactivator complex results from interactions involving the sulfenyl sulfur atom of the S-sulfo amino acid and the active site thiol group of the enzyme. PMID- 2890641 TI - Early effects of beta-adrenergic and muscarinic secretagogues on lipid and phospholipid metabolism in guinea pig parotid acinar cells. Stimulation of 2,3-sn diacylglycerol formation by isoproterenol. AB - The early effects (0-120 s) of the beta-adrenergic secretagogue isoproterenol (2.10(-5) M) and the muscarinic secretagogue carbamoylcholine (2.10(-6) M) on various parameters of lipid and phospholipid metabolism were studied in isolated guinea pig parotid acinar cells. Both agonists enhanced within 10-20 s the incorporation of radioactive palmitate into the diacylglycerol, the triglyceride, and the phosphatidylinositol fractions but significantly diminished radioactive palmitate recovered in the acyl-CoA fraction. Carbamoylcholine decreased and isoproterenol increased the recovery of radioactive palmitate in the free fatty acid fraction. All changes had returned almost to control levels after 120 s. In cells prelabeled with [3H]arachidonate, carbamoylcholine exerted similar effects, whereas isoproterenol was almost ineffective. Both agonists stimulated the incorporation of radioactive glycerol into diacylglycerols 2-3-fold, while only carbamoylcholine stimulated the incorporation of [32P]phosphate into phosphatidylinositol and phosphatidate. Both agonists induced an increase in total diacylglycerols, carbamoylcholine being about twice as effective as isoproterenol. A lower concentration of carbamoylcholine (6.5.10(-7) M) had the same quantitative effect as 2.10(-5) M isoproterenol on the increase of total diacylglycerols. Even under these conditions carbamoylcholine, but not isoproterenol led to a significant translocation of protein kinase C from the soluble to the particulate fraction. Isoproterenol remained ineffective in this respect also when intracellular free calcium was increased with a calcium ionophore. This is explained by the finding that isoproterenol stimulates preferentially the formation of 2,3-sn-diacylglycerol, and carbamoylcholine preferentially stimulates the formation of 1,2-sn-diacylglycerol. The results indicate that in the guinea pig parotid acinar cell the two agonists do not only lead to activation of a triglyceride lipase (isoproterenol) or phosphoinositide specific phospholipase(s) (carbamoylcholine), but also to a rapid change of flux through a number of other enzyme-catalyzed reactions involved in diacylglycerol turnover. PMID- 2890642 TI - The GDP-fucose:N-acetylglucosaminide 3-alpha-L-fucosyltransferases of LEC11 and LEC12 Chinese hamster ovary mutants exhibit novel specificities for glycolipid substrates. AB - Previous studies have shown that the GDP-fucose:N-acetylglucosaminide 3-alpha-L fucosyltransferase (alpha (1,3) fucosyltransferase (Fuc-T)) activities expressed by the Chinese hamster ovary cell mutants LEC11 (Fuc-TI) and LEC12 (Fuc-TII) are different enzymes and indicated that Fuc-TI might act on sialylated lactosamine sequences (Campbell, C., and Stanley, P. (1984) J. Biol. Chem. 259, 11208-11214). In this paper we show that CSLEX-1, a monoclonal antibody specific for NeuNac alpha (2,3)Gal beta (1,4)(Fuc alpha (1,3))GlcNAc beta 1 sequences, bound to LEC11 cells but not to LEC12 cells. Direct evidence that Fuc-TI could act on sialylated substrates was sought with a series of glycolipid acceptors. Optimal assay conditions in crude cell extracts were determined with nLc4, a glycolipid which accepted fucose with both Fuc-TI and Fuc-TII to generate the Lex antigenic determinant. The two enzymes differed in their detergent sensitivities, pH optima, Mn2+ requirements, and apparent Km values for nLc4. When sialylated glycolipids were examined as substrates, Fuc-TI added fucose to IV3NeuNAcnLc4 but not to IV6NeuNAcnLc4, whereas Fuc-TII was unable to utilize either glycolipid as a substrate. Further studies showed that Fuc-TI and Fuc-TII possess novel specificities for glycolipids containing two lactosamine sequences as potential fucose acceptors. Fuc-TI exhibited good activities with VI3NeuNAcnLc6 and VI6NeuNAcnLc6 whereas Fuc-TII had very low activity with both substrates. Glycosidase digestions of the labeled products showed that Fuc-TI added fucose primarily to the internal N-acetylglucosamine of both glycolipids. The same preference for the internal N-acetylglucosamine was shown by Fuc-TI when nLc6 was the acceptor. In contrast, Fuc-TII preferred to transfer fucose to the external acceptor site of nLc6, consistent with the low activities of Fuc-TII with sialylated nLc6 derivatives. Thus the two enzymes preferentially add fucose to different N-acetylglucosamines in the same substrate, nLc6. This indicates that the biosynthetic pathway for fucosylation of polylactosamine sequences in glycolipids and glycoproteins will vary depending upon the particular alpha (1,3)fucosyltransferase present. PMID- 2890643 TI - Structural determination of the oligosaccharide side chains from a glycoprotein isolated from the mucus of the coral Acropora formosa. AB - An extracellular mucous glycoprotein has been isolated from the hard coral Acropora formosa. The glycoprotein contains sulfated oligosaccharide side chains attached through O-glycosidic linkages to serine and threonine, the principal amino acids (77%) in the polypeptide. The oligosaccharide side chains consist of D-arabinose, D-mannose, and N-acetyl-D-glucosamine with smaller amounts of D galactose, L-fucose, and N-acetyl-D-galactosamine, but no sialic or uronic acids. Alkaline borohydride reductive cleavage resulted in a mixture of oligosaccharide alditols. Six oligosaccharides were purified by high performance liquid chromatography. The structures of these oligosaccharides, which do not resemble those of any other glycoprotein so far examined, were determined by a combination of gas chromatography/mass spectrometry analysis of methylation products and NMR spectroscopy. All oligosaccharides contain a reducing terminal mannitol residue with N-acetylglucosamine linked to carbon 2, 4, or 6 of the mannitol. There is no evidence for linkage of N-acetylglucosamine to any other glycoses in the glycoprotein. Galactose was detected in two oligosaccharides linked to the 4 position of mannitol. Arabinose (Ara) was found in only one oligosaccharide. This was probably due to hydrolysis of the labile arabino-furanoside linkages. Evidence is presented which indicates the arabinose occurs primarily at the terminal position of oligosaccharide side chains. The structures of the oligosaccharides isolated from the glycoprotein were: (Formula: see text). PMID- 2890644 TI - Clathrin assembly proteins: affinity purification and a model for coat assembly. AB - Assembly protein (AP) preparations from bovine brain coated vesicles have been fractionated by clathrin-Sepharose affinity chromatography. Two distinct fractions that possess coat assembly activity were obtained and are termed AP-1 and AP-2. The AP-1, not retained on the resin, has principal components with molecular weights of 108,000, 100,000, 47,000, and 19,000. The AP-2, bound to the resin and eluted by Tris-HCl at a concentration that parallels the latter's effect on coat disassembly, corresponds to the active complex described previously (Zaremba, S., and J. H. Keen, 1983, J. Cell Biol., 97:1339-1347). Its composition is similar to that of the AP-1 in that it contains 100,000-, 50,000-, and 16,000-mol-wt polypeptides in equimolar amounts; minor amounts of 112,000- and 115,000-mol-wt polypeptides are also present. Both are distinct from a recently described assembly protein of larger subunit molecular weight that we term AP-3. These results indicate the existence of a family of assembly proteins within cells. On incubation with clathrin both AP-1 and AP-2 induce the formation of coat structures, those containing AP-1 slightly smaller (mean diameter = 72 nm) than those formed in the presence of AP-2 (mean diameter = 79 nm); both structures have been detected previously in coated vesicle preparations from brain. Coats formed in the presence of AP-2 consistently contain approximately one molecule each of the 100,000-, 50,000-, and 16,000-mol-wt polypeptides per clathrin trimer. By low angle laser light scattering the molecular weight of native AP-2 was determined to be approximately 343,000, indicating that it is a dimer of each of the three subunits, and implying that it is functionally bivalent in clathrin binding. A model for AP-mediated coat assembly is proposed in which a bivalent AP-2 molecule bridges the distal legs or terminal domains of two clathrin trimers that are destined to occupy adjacent vertices in the assembled coat. Binding of a second AP-2 molecule locks these two trimers in register for assembly and further addition of AP-2 to free trimer legs promotes completion of the clathrin lattice. Effects of AP binding on the angle and flexibility of the legs at the hub of the trimer (the "pucker") are suggested to account for the characteristic size distributions of coats formed under varied conditions and, more speculatively, to contribute to the transformation of flat clathrin lattices to curved coated vesicles that are thought to occur during endocytosis. PMID- 2890645 TI - A microtubule-associated protein from Xenopus eggs that specifically promotes assembly at the plus-end. AB - We have isolated a protein factor from Xenopus eggs that promotes microtubule assembly in vitro. Assembly promotion was associated with a 215-kD protein after a 1,000-3,000-fold enrichment of activity. The 215-kD protein, termed Xenopus microtubule assembly protein (XMAP), binds to microtubules with a stoichiometry of 0.06 mol/mol tubulin dimer. XMAP is immunologically distinct from the Xenopus homologues to mammalian brain microtubule-associated proteins; however, protein species immunologically related to XMAP with different molecular masses are found in Xenopus neuronal tissues and testis. XMAP is unusual in that it specifically promotes microtubule assembly at the plus-end. At a molar ratio of 0.01 mol XMAP/mol tubulin the assembly rate of the microtubule plus-end is accelerated 8 fold while the assembly rate of the minus-end is increased only 1.8-fold. Under these conditions XMAP promotes a 10-fold increase in the on-rate constant (from 1.4 s-1.microM-1 for microtubules assembled from pure tubulin to 15 s-1.microM 1), and a 10-fold decrease in off-rate constant (from 340 to 34 s-1). Given its stoichiometry in vivo, XMAP must be the major microtubule assembly factor in the Xenopus egg. XMAP is phosphorylated during M-phase of both meiotic and mitotic cycles, suggesting that its activity may be regulated during the cell cycle. PMID- 2890646 TI - Differential effects of temperature on cAMP-induced excitation, adaptation, and deadaptation of adenylate and guanylate cyclase in Dictyostelium discoideum. AB - Extracellular cAMP induces excitation of adenylate and guanylate cyclase in Dictyostelium discoideum. Continuous stimulation with cAMP leads to adaptation, while cells deadapt upon removal of the cAMP stimulus. Excitation of guanylate cyclase by cAMP has a lag time of approximately 1 s; excitation of adenylate cyclase is much slower with a lag time of 30 s. Excitation of both enzyme activities is less than twofold slower at 0 degrees C than at 20 degrees C. Adaptation of guanylate cyclase is very fast (t1/2 = 2.4 s at 20 degrees C), and virtually absent at 0 degrees C. Adaptation of adenylate cyclase is much slower (t1/2 = 110 s at 20 degrees C) but not very temperature sensitive (t1/2 = 290 s at 0 degrees C). At 20 degrees C, deadaptation of adenylate cyclase is about twofold slower than deadaptation of guanylate cyclase (t1/2 = 190 and 95 s, respectively). Deadaptation of adenylate cyclase is absent at 0 degrees C, while that of guanylate cyclase proceeds slowly (t1/2 = 975 s). The results show that excitation, adaptation, and deadaptation of guanylate cyclase have different kinetics and temperature sensitivities than those of adenylate cyclase, and therefore are probably independent processes. PMID- 2890647 TI - Multiple type-beta transforming growth factors and their receptors. AB - Type beta transforming growth factors are a group of homologous structurally related polypeptides that act on a wide variety of cell types to alter their proliferative and phenotypic properties. TGF-beta s form a group within a larger family of polypeptides that control developmental processes in organisms from humans to Drosophila. We have found that at least three distinct forms of TGF beta are present in mammalian tissues. We have identified a family of cell surface glycoproteins that bind TGF-beta s with high affinity and specificity. Examination of the interactions between individual forms of TGF-beta and the individual TGF-beta receptor species has illustrated a complex pattern of ligand receptor associations. Occupancy of a particular receptor type by TGF-beta can be correlated to the dictation of specific effects on cell proliferation and cell differentiation. PMID- 2890648 TI - Ornithine decarboxylase activity during rat spermatogenesis in vivo and in vitro: selective effect of hormones and growth factors. AB - We have established the patterns of ornithine decarboxylase activity (an enzyme related to cell growth, differentiation, and proliferation) during rat testicular development and studied the effect of epidermal growth factor (EGF), platelet derived growth factor (PDGF), transforming growth factor-type beta (TGF-beta), and a serum-free, hormone/growth factor-supplemented medium (TKM) on ornithine decarboxylase (ODC) activity in Sertoli-spermatogenic cell cocultures and cultured seminiferous peritubular cells prepared from sexually immature rats (20 22 days old). Results were correlated with timing of ODC activities during rat testicular development. We have found that: (1) although EGF, alone or combined with PDGF and TGF-beta, and TKM stimulated ODC activity in Sertoli-spermatogenic cell cocultures after 6 and 24 h of stimulation, PDGF exerted an inhibitory effect, and (2) cultured peritubular cells stimulated with EGF, PDGF, TGF-beta (and their combinations), and TKM displayed an increase in ODC activity after 6 h of stimulation, but ODC activities for most of these treatments declined considerably 24 h after stimulation. Light microscopic autoradiographic studies of [3H]thymidine labeled samples demonstrated that (1) clones of spermatogenic cells traverse S phase synchronously, (2) Sertoli cells are not significantly radiolabeled, probably because of contact inhibition achieved by high cell plating density, and (3) peritubular cells are significantly [3H]thymidine labeled in the presence of TKM, a culture medium that facilitates spermatogenic cell long-term viability and differentiation. We conclude that TKM and EGF have stimulatory effects on the biochemical pathway that precedes synchronous DNA synthesis in spermatogonia and preleptotene spermatocytes, and that ODC activity is a sensitive marker for monitoring these events. PMID- 2890649 TI - 'Elephant man' with severe hypertension. PMID- 2890650 TI - Separation of racemic pharmaceuticals by high-performance liquid chromatography on silica gel modified with carbohydrate residues. AB - Derivatives of 2-amino-2-deoxyglucose covalently connected to aminopropyl-silica gel were used as chiral selectors in the separation of racemic pharmaceuticals. beta-Receptor blockers, adrenergic drugs and compounds with secondary amino functions could be separated after appropriate derivatization. PMID- 2890651 TI - An enzyme immunoassay for dengue antibody using infected cultured mosquito cells as antigen. AB - A simple enzyme immunoassay (EIA) for dengue virus antibody detection used infected tissue culture cells as antigen. C6/36 Aedes albopictus cells infected with dengue virus, and uninfected control cells were fixed with 3.3% formalin. This technique eliminated microplate coating and laborious antigen preparation, and it facilitated rapid screening of large numbers of sera. Formalin also inactivated dengue virus infectivity. Microplates prepared by this technique could be stored at -20 or -70 degrees C for at least two months. Human sera were adsorbed with C6/36 cells prior to testing in the EIA in order to reduce nonspecific binding to C6/36 cells. PMID- 2890652 TI - Use of enzyme immunoassay and nucleic acid hybridization for detecting Sindbis virus in infected mosquitoes. AB - Aedes aegypti mosquitoes were inoculated intrathoracically with prototype Sindbis virus, held at 26.7 degrees C for from 0-95 h and placed at -70 degrees C. Individual mosquitoes were tested for virus by plaque assay in Vero cells, for viral RNA by nucleic acid hybridization using a cloned cDNA probe, and for viral protein by enzyme-linked immunosorbent assay. Virus was detected by plaque assay as early as 8 h after infection. Sindbis virus RNA was detected by nucleic acid hybridization 18 h after infection and by enzyme-linked immunosorbent assay 10 h after infection. The results of these comparisons suggest that both nucleic acid hybridization and enzyme-linked immunosorbent assay are applicable to direct detection of Sindbis virus in mosquitoes containing virus at levels usually found during arbovirus epidemics. PMID- 2890653 TI - Neuroendocrine regulation of thyrotropin release in cultured human pituitary cells. AB - The regulation of TSH release in man was investigated using cell cultures derived from human pituitaries obtained within 24 h of accidental death. TRH stimulated TSH release in a dose-dependent manner. The ED50 was 2.9 +/- 0.6 (+/- SEM) nmol/L, similar to that reported for rat pituitary cell cultures. The release of TSH was calcium dependent, since the calcium channel antagonist verapamil inhibited TRH-stimulated TSH release, and the calcium ionophore A23187 stimulated TSH release. 12-O-Tetradecanoyl-phorbol-13-acetate stimulated TSH secretion, while dibuytryl cAMP had no effect. Epinephrine and serotonin stimulated TSH release, and dopamine and somatostatin inhibited TRH-stimulated TSH release. These findings have directly demonstrated that the regulation of TSH secretion by hypothalamic neuropeptides and biogenic amines in the human pituitary is similar to that in the rat. The development of a tissue culture system to study thyrotrophs from postmortem human pituitaries provides the means for detailed studies of the regulation of TSH secretion in man. PMID- 2890654 TI - Isolation of the galactose-binding lectin that mediates the in vitro adherence of Entamoeba histolytica. AB - Entamoeba histolytica adheres to human colonic mucus, colonic epithelial cells, and other target cells via a galactose (Gal) or N-acetyl-D-galactosamine (GalNAc) inhibitable surface lectin. Blockade of this adherence lectin with Gal or GalNAc in vitro prevents amebic killing of target cells. We have identified and purified the adherence lectin by two methods: affinity columns derivatized with galactose monomers or galactose terminal glycoproteins, and affinity columns and immunoblots prepared with monoclonal antibodies that inhibit amebic adherence. By both methods the adherence lectin was identified as a 170-kD secreted and membrane-bound amebic protein. The surface location of the lectin was confirmed by indirect immunofluorescence. Purified lectin competitively inhibited amebic adherence to target cells by binding to receptors on the target Chinese hamster ovary cells in a Gal-inhibitable manner. PMID- 2890655 TI - Rat and human colonic mucins bind to and inhibit adherence lectin of Entamoeba histolytica. AB - Establishment of adherence by Entamoeba histolytica is mediated by a 170-kD Gal/GalNAc inhibitable lectin and is required for cytolysis and phagocytosis of mammalian target cells. We studied the biochemical mechanisms of the in vitro interaction between rat and human colonic mucins and axenic E. histolytica trophozoites. Crude mucus prevented amebic adherence to Chinese hamster ovary (CHO) cells by up to 70%. Purification of the colonic mucins by Sepharose 4B chromatography, nuclease digestion, and cesium chloride gradient centrifugation resulted in a 1,000-fold enrichment of the inhibitory mucins. Purified rat mucin inhibited amebic adherence to and cytolysis of homologous rat colonic epithelial cells. Oxidation and enzymatic cleavage of rat mucin Gal and GalNAc residues completely abrogated mucin inhibition of amebic adherence. The binding of rat 125I-mucin to amebae was galactose specific, saturable, reversible, and pH dependent. A monoclonal antibody specific for the 170-kD amebic Gal/GalNAc lectin completely inhibited the binding of rat 125I-mucin. Rat mucin bound to Affigel affinity purified the amebic lectin from conditioned medium. Colonic mucin glycoproteins act as an important host defense by binding to the parasite's adherence lectin, thus preventing amebic attachment to and cytolysis of host epithelial cells. PMID- 2890656 TI - Endothelium-dependent responses in autogenous femoral veins grafted into the arterial circulation of the dog. AB - Endothelium-dependent responses differ in arteries and veins of the dog. Experiments were performed to determine whether chronic grafting of veins into the arterial circulation would alter the endothelium-dependent responses of the veins. Segments of femoral veins were grafted to the femoral artery of the dog. 6 wk after surgery the venous grafts were removed from the dog, cut into rings, and suspended in organ chambers for isometric tension recording. In some rings the endothelial cells were removed. Acetylcholine and alpha 2-adrenergic agonists did not cause endothelium-dependent relaxations in venous grafts. The calcium ionophore (A23187) initiated such relaxations which were not mediated by prostanoids. Endothelium-dependent relaxations were also observed in venous grafts to ADP, thrombin, and arachidonic acid. In segments of graft where myo intimal hyperplasia was prominent, relaxations to ADP, thrombin, and A23187 were blunted and in some segments contractions were observed. These results demonstrate the ability of the endothelium of venous grafts to initiate changes in tone of the smooth muscle. PMID- 2890657 TI - Cytoprotective effects of glycine and glutathione against hypoxic injury to renal tubules. AB - Roles for both the tripeptide, GSH, and individual amino acids in modifying the cellular response to oxygen deprivation-induced injury have been suggested by prior work in kidney and other tissues, but the precise interrelationships have not been clearly defined. We have studied the effects of GSH, its component amino acids, and related compounds on the behavior of isolated renal proximal tubules in a well characterized model of hypoxic injury in vitro. GSH, the combination of cysteine, glutamate, and glycine and glycine alone, when present in the medium during 30 min hypoxia, a duration sufficient to produce extensive irreversible injury in untreated tubules, were protective. Significant effects were detected at 0.25 mM concentrations of the reagents, and protection was nearly complete at concentrations of 1 mM and above. Glutamate and cysteine alone were not protective. The exogenous GSH added to the tubule suspensions was rapidly degraded to its component amino acids. Treatment of tubules with GSH or cysteine, but not glycine, increased intracellular GSH levels. Oxidized GSH was protective. Serine, N-(2-mercaptopropionyl)-glycine, and a panel of agents known to modify injury produced by reactive oxygen metabolites were without benefit. These observations identify a novel and potent action of glycine to modify the course of hypoxic renal tubular cell injury. This effect is independent of changes in cellular GSH metabolism and appears to be unrelated to alterations of cell thiols or reactive oxygen metabolites. Further elucidation of its mechanism may provide insight into both the basic pathophysiology of oxygen deprivation-induced cell injury and a practical way to ameliorate it. PMID- 2890658 TI - Selective binding of somatostatin-14 and somatostatin-28 to islet cells revealed by quantitative electron microscopic autoradiography. AB - Quantitative electron microscopic autoradiography was used for comparing the binding of labeled somatostatin-14 (S-14) and somatostatin-28 (S-28 section) to islet cells. Monolayer cultures of rat islet cells were incubated with [125I Tyr11]S-14 (S-14 section) or [125I-Leu8, D-Trp22, Tyr25]S-28 (S-28 section) in the presence or absence of excess unlabeled peptides. Autoradiographic grains (ARG) associated with individual islet cells were identified and expressed as the mean number per B, A, and D cells. Specific ARG associated with S-14 were found over B and A cells. S-28 section-related specific ARG were concentrated over B, A, as well as D cells. The highest density of S-14 section labeling occurred over A cells, which under conditions of maximum labeling (37 degrees C for 60 min) contained five times as many ARG as did B cells. By contrast, under the same incubation conditions, the labeling density with S-28 section was maximal over B cells, which contained four and five times as many grains as A and D cells, respectively. These observations show preferential association of S-14 section with the A cell and S-28 section with the B cel provide strong evidence for the existence of separate binding sites for S-14 section and S-28 section on A and B cells, respectively, which presumably mediate the previously reported glucagon selective inhibitory effect of S-14 and the insulin-selective action of S-28. PMID- 2890659 TI - Restriction fragment length polymorphism of the C1 inhibitor gene in hereditary angioneurotic edema. AB - Hereditary angioneurotic edema (HANE) results from the deficiency of the inhibitor of the first component of human complement (C1-INH). It is inherited as an autosomal dominant trait. Heterogeneity of this defect has been shown at the protein and mRNA level. Southern blot analysis of genomic DNA was performed after digestion with six different restriction endonucleases in 24 families affected with type 1 HANE (low antigenic and functional C1-INH levels) and five with type 2 (low functional C1-INH levels and normal or elevated levels of dysmorphic C1 INH). Blots were hybridized with a C1-INH cDNA probe of 1,227 bp. With one enzyme (Pst I), two different patterns of restriction fragment length polymorphism (RFLP) were detected. One was present in one kindred with type 1 HANE and the other appeared the same in one type 1 and in one type 2 family, thus indicating that each RFLP resulted from a different mutation. Analysis of a total of 34 members of these three families suggested that the polymorphisms are tightly linked to the mutation responsible for the disease. Using a 170-bp probe we showed that the three different mutations leading to these polymorphisms are located in the same region of the C1-INH gene. These data suggest that different mutations in the same region of the C1-INH gene are responsible for C1-INH deficiency in these families. Most of these mutations are probably point mutations or other "minor" defects and do not appear to be due to major deletions or rearrangements. PMID- 2890660 TI - Effect of adrenergic and muscarinic cholinergic agonists on atrial natriuretic peptide secretion by isolated rat atria. Potential role of the autonomic nervous system in modulating atrial natriuretic peptide secretion. AB - Stretching of the atrial wall is a known stimulant for atrial natriuretic peptide (ANP) secretion. Little is known about other factors that may influence ANP secretion. We examined the effects of the neurotransmitters of the autonomic nervous system on ANP secretion from isolated rat left atria. Superfusion with 10 muM norepinephrine produced a biphasic rise in ANP secretion with a peak response 2.5-fold above baseline secretion. To determine whether the response to norepinephrine primarily reflected alpha- or beta-adrenergic receptor stimulation, atria were superfused with 0.1 muM isoproterenol or 10 muM phenylephrine and 1 muM propranolol. ANP secretion in response to isoproterenol was biphasic, similar to the response to norepinephrine. Phenylephrine evoked a monophasic ANP secretory response, which was delayed in onset relative to that of isoproterenol or norepinephrine. Superfusion with 10 muM methacholine alone had no effect on ANP secretion, but rapidly attenuated norepinephrine-stimulated secretion by 67%. From these observations we conclude: (a) Both alpha- and beta adrenergic agonists directly and distinctively stimulate ANP secretion; (b) Norepinephrine stimulates ANP secretion by both alpha- and beta-adrenergic mechanisms, however the secretory response pattern of norepinephrine reflects a predominence of beta-adrenergic activity; (c) Under basal conditions, methacholine does not influence ANP secretion; and (d) Methacholine inhibits norepinephrine-stimulated ANP secretion. Thus, in vivo, activation of the sympathetic nervous system may enhance ANP secretion, whereas a rise in parasympathetic tone may lower ANP secretion. PMID- 2890661 TI - Alpha 2 adrenergic agonists stimulate Na+-H+ antiport activity in the rabbit renal proximal tubule. AB - The role of adrenergic agents in augmenting proximal tubular salt and water flux, was studied in a preparation of freshly isolated rabbit renal proximal tubular cells in suspension. Norepinephrine (NE, 10(-5) M) increased sodium influx (JNa) 60 +/- 5% above control value. The alpha adrenergic antagonist, phentolamine (10( 5) M), inhibited the NE-induced enhanced JNa by 90 +/- 2%, while the beta adrenergic antagonist, propranolol, had a minimal inhibitory effect (10 +/- 2%). The alpha adrenergic subtype was further defined. Yohimbine (10(-5) M), an alpha2 adrenergic antagonist but not prazosin (10(-5) M), an alpha1 adrenergic antagonist completely blocked the NE induced increase in JNa. Clonidine, a partial alpha2 adrenergic agonist, increased JNa by 58 +/- 2% comparable to that observed with NE (10(-5) M). Yohimbine, but not prazosin, inhibited the clonidine induced increase in JNa, confirming that alpha2 adrenergic receptors were involved. Additional alpha2 adrenergic agents, notably p-amino clonidine and alpha-methyl-norepinephrine, imparted a similar increase in JNa. The clonidine induced increase in JNa could be completely blocked by the amiloride analogue, ethylisopropyl amiloride (EIPA, 10(-5) M). The transport pathway blocked by EIPA was partially inhibited by Li and cis H+, but stimulated by trans H+, consistent with Na+-H+ antiport. Radioligand binding studies using [3H]prazosin (alpha1 adrenergic antagonist) and [3H]rauwolscine (alpha2 adrenergic antagonist) were performed to complement the flux studies. Binding of [3H]prazosin to the cells was negligible. In contrast, [3H]rauwolscine showed saturable binding to a single class of sites, with Bmax 1678 +/- 143 binding sites/cell and KD 5.4 +/- 1.4 nM. In summary, in the isolated rabbit renal proximal tubular cell preparation, alpha2 adrenergic receptors are the predominant expression of alpha adreno receptors, and in the absence of organic Na+-cotransported solutes, alpha2 adrenergic agonists enhance 22Na influx into the cell by stimulating the brush border membrane Na+-H+ exchange pathway. PMID- 2890662 TI - Adaptation of methods for glutamate dehydrogenase and alcohol dehydrogenase activities to a centrifugal analyser: assessment of their clinical use in anoxic states of the liver. AB - Sensitive, precise, and rapid methods for the measurement of alcohol dehydrogenase (ADH) and glutamate dehydrogenase (GDH) were developed on the Cobas Bio centrifugal analyser. The optimal pH for ADH in caucasians was 9.8. Non linearity of ADH enzyme activity was observed when samples were diluted in saline; linearity was restored when inactivated serum was used as diluent. ADH was shown to be a sensitive index of liver anoxia due to cardiorespiratory disturbance (clinical sensitivity 90%) and generalised anoxia. GDH exhibited sensitivity equal to that of alanine aminotransferase (ALT) but was inferior to gamma-glutamyltransferase (GGT) in the detection of specific liver disease. Both ADH and GDH were sensitive indicators of alcoholic liver disease. PMID- 2890663 TI - Plasma intestinal alkaline phosphatase and intermediate molecular mass gamma glutamyltransferase activities in the differential diagnosis of jaundice. AB - An assessment was made of the value of: (i) the demonstration of intestinal alkaline phosphatase in plasma for the differentiation of intrahepatic from post hepatic jaundice in 122 jaundiced patients; and (ii) the demonstration of an intermediate molecular mass gamma glutamyltransferase in plasma for the identification of post-hepatic cholestasis in 74 jaundiced patients. The first test had a diagnostic sensitivity of only 32% with a specificity of 86%; the second test had a sensitivity of 50% and specificity of 75%. It is concluded that neither procedure is worth while. PMID- 2890664 TI - Pharmacokinetics and pharmacodynamics of flestolol, a new short-acting, beta adrenergic receptor antagonist. AB - The pharmacokinetics and pharmacodynamics of flestolol, a new short-acting, beta adrenergic receptor antagonist, were examined in nine healthy subjects after a constant intravenous infusion of 5 micrograms/kg/min for 72 hours. Flestolol blood levels were determined by high-performance liquid chromatography. In all subjects, flestolol blood concentration attained steady state 30 minutes after initiation of infusion. The mean +/- standard deviation steady-state concentration of flestolol was 31.1 +/- 12.0 ng/mL. The elimination half-life averaged 7.2 minutes. The mean +/- standard deviation total body clearance was 181 +/- 66 mL/min/kg. The apparent volume of distribution and the area under the curve averaged 1.89 L/kg and 2.23 micrograms-hr/mL, respectively. Flestolol did not cause any significant change (P greater than .05) in the heart rate or systolic or diastolic blood pressure from the baseline. Flestolol significantly (P less than .05) attenuated the isoproterenol-induced increase in heart rate and systolic blood pressure and decrease in diastolic blood pressure in comparison with baseline. The average maximum reduction in isoproterenol tachycardia was in the range of 63% to 79% during flestolol infusion. There was a rapid recovery from beta blockade after termination of flestolol infusion; the recovery averaged 96% 20 minutes after the infusion was stopped. We conclude that flestolol exhibits a very short half-life and is cleared mainly by extrahepatic routes. It is an effective beta blocker and possesses a short duration of action. PMID- 2890665 TI - The acute and chronic effects of betaxolol on blood pressure, renin-aldosterone, and renal function in essential hypertension. AB - The effects of betaxolol, a long-acting, lipid-soluble, cardioselective, beta adrenergic antagonist on renal function have not been previously reported. The present study was designed to prospectively assess the acute and chronic antihypertensive, humoral, and renal response to betaxolol, administered once daily, to patients with essential hypertension. After a four-week placebo run-in period, 13 patients with essential hypertension were treated with betaxolol monotherapy for a total of eight months. Results indicate that blood pressure is reduced, and renal function remains stable. These findings are consistent with previous observations with other beta-adrenergic antagonists. PMID- 2890666 TI - Nocturnal doses of ranitidine and nizatidine do not affect the disposition of diazepam. AB - The disposition of diazepam (D) after a single oral dose of 10 mg was evaluated in nine healthy male volunteers under the following conditions (randomized, double-blind, crossover design): D + comedication of placebo and D + nocturnal dosing with 300 mg ranitidine or 300 mg nizatidine. Plasma concentrations of D and its major active metabolite, desmethyldiazepam (DD), were monitored by a gas liquid chromatography-electron-capture detection assay for 84 hours. Neither ranitidine nor nizatidine had any significant effect on the hepatic elimination of D as characterized by its terminal half-life (mean +/- SD) of 35.3 +/- 24.2 hours (+ ranitidine: 30.1 +/- 9.9 hr; + nizatidine: 37.3 +/- 18.3 hr) or total plasma clearance of 28.2 +/- 12.0 mL/min (+ ranitidine: 26.5 +/- 7.9 mL/min; + nizatidine: 26.7 +/- 10.4 mL/min). Likewise, the formation of DD as measured by its AUC was not affected by ranitidine or nizatidine. Thus, it can be concluded that concomitant once-daily dosing (300 mg nocturnally) with ranitidine or nizatidine does not impair hepatic drug metabolism. PMID- 2890667 TI - Sulfasalazine and related new drugs. PMID- 2890668 TI - The influence of food on the oral absorption of bevantolol. AB - The bioavailability of bevantolol was compared in 12 healthy volunteers given single doses of the drug as the HCl salt after an overnight fast, or 15 minutes before or after a standardized breakfast in a nonblind, randomized crossover design. Bevantolol was rapidly absorbed in all three treatment groups, with maximum concentrations (Cmax) observed at 1.0, 0.9, and 1.8 hours for the fasting, before breakfast, and after breakfast groups, respectively. Time to Cmax was significantly longer than fasting only when bevantolol was given after breakfast. Food ingestion did not significantly affect Cmax, total of absorbed drug, or the drug elimination rate. Since food only slightly decreases the drug absorption rate and has no measurable effect on the extent of drug absorption, the relationship of bevantolol administration to meals is not expected to influence therapeutic efficacy. PMID- 2890669 TI - Hemodynamic effects during rest and exercise of bucindolol in hypertensive men. AB - Bucindolol is an investigational beta-adrenergic blocking agent with intrinsic sympathomimetic and vasodilatory activity in animals. In a double-blind, six-way, crossover study of six mild-to-moderate hypertensive men, the effects of bucindolol 100, 200, and 300 mg/d on resting blood pressure, heart rate, forearm blood flow, and vascular resistance measured by pneumoplethysmography, and blood pressure and heart rate after cycle and handgrip exercise were compared with those of propranolol 160 and 320 mg/d and placebo after q12h administration for five doses. Both bucindolol and propranolol significantly suppressed heart rate after cycle exercise in comparison with placebo (-33 to -48 beats/min), demonstrating beta blockade. Suppression of resting heart rate by propranolol ( 20 beats/min) was significantly (P less than .05) greater than bucindolol (-7 to 8 beats/min); a similar treatment difference in heart rate was noted after handgrip exercise (-18 to -19 vs -1 to -8 beats/min, respectively). Bucindolol and propranolol decreased resting blood pressure to the same extent (in comparison with placebo; P less than .05 at peak activity, 2 hr postdose). Bucindolol tended to increase forearm blood flow and decrease forearm vascular resistance (P less than .05 at 4 hr postdose) in comparison with placebo. The effect of propranolol on forearm blood flow and forearm vascular resistance was not significant compared with placebo. These data are consistent with intrinsic sympathomimetic and vasodilatory activity of bucindolol in hypertensive men. PMID- 2890670 TI - Respiratory effects of quazepam and pentobarbital. AB - Quazepam is a new benzodiazepine that may provide good hypnotic action with negligible effect on motor coordination or respiration. Sleep laboratory studies on human volunteers have shown quazepam 15 mg to be an effective hypnotic dose, with the 30-mg dose being optimal. At these doses, there was no deterioration of motor performance, and the drug, when given nightly for two weeks, continued to exert hypnotic effects without serious adverse effects. Therefore, this study was designed to compare the respiratory effects of quazepam 15 and 30 mg to those of pentobarbital 50 and 150 mg and to placebo. Five adult male volunteers received each dose at separate times. A double-blind technique was employed for controlled rebreathing studies, to a ventilation of 40 L/min or a PETCO2 of 8%. Respiratory curves were compared with controls. The mean displacement curve at the 20-liter intercept showed a depressant effect for pentobarbital 150 mg at two hours and a stimulant effect for quazepam 15 mg at two hours but a slight depression effect for quazepam 30 mg at three hours compared with placebo. The slope of the respiratory curve was not affected. PMID- 2890671 TI - The efficacy of piquindone, a new atypical neuroleptic, in the treatment of the positive and negative symptoms of schizophrenia. AB - Piquindone (RO22-1319), a new "atypical" neuroleptic, was administered for 2 weeks to 37 schizophrenic patients, and the effects of treatment were examined in a double-blind, placebo-controlled trial. "Atypical" neuroleptics are those that block animal behaviors that model antipsychotic actions in humans at doses lower than those necessary to block animal behaviors that model extrapyramidal actions. Our results demonstrate that piquindone led to moderate but significant improvements in the positive symptoms of schizophrenia and to improvements in negative symptoms just below the level of statistical significance. This supports the notion that neuroleptics categorized as "atypical" in preclinical experiments may prove to be clinically efficacious in humans. In addition, our anecdotal observations were that piquindone caused minimal extrapyramidal symptoms. This is consistent with the preclinical data and suggests that atypical neuroleptics may be associated with fewer extrapyramidal side effects in humans than conventional neuroleptics. However, this must be substantiated by further research. PMID- 2890672 TI - Prediction of neuroleptic-induced dystonia. AB - For patients receiving neuroleptics, age, sex, neuroleptic potency, and dose all influence the likelihood of a dystonic reaction. Little is known, however, of the relative importance of these factors or of the feasibility of predicting dystonia in individual patients. We reviewed 135 charts of psychotic inpatients to examine these factors and their usefulness in predicting dystonia. Age, sex, neuroleptic type, dose, and occurrence of dystonia were recorded for the first 4 days of drug treatment and were used to construct a linear discriminant function that classified the cases as to whether dystonia was expected. Internal cross validation was performed, and the error rate of this classification procedure was calculated. Forty-nine (36%) of the patients had dystonia. A younger age was the most powerful predictor of dystonia. Male gender was second in predictive power with minor effects from neuroleptic dose and potency. The overall error rate (false-positive and false-negative errors combined) of the discriminant function was 30%. These results suggest the possibility of predicting dystonia in individual patients but should be regarded with caution since the predictive procedure has not been tested prospectively. If confirmed, these data may allow treatment strategies that protect patients from dystonia while sparing patients not at risk unnecessary treatment with antiparkinson agents. PMID- 2890673 TI - Treatment of negative symptoms in schizophrenia with zotepine. PMID- 2890674 TI - Clinical evolution of cutaneous T cell lymphoma in a patient with antibodies to human T-lymphotropic virus type I. AB - A woman who emigrated to the United States from the Dominican Republic developed the first signs of cutaneous T cell lymphoma during the last trimester of her pregnancy. This patient, found to have a positive reaction against human T lymphotropic (leukemia-lymphoma) virus type I (HTLV-I), was followed up prospectively from the appearance of the initial skin lesion to the development of high-count helper T cell leukemia. Antibodies reactive with the core protein of HTLV-I were also identified in her husband and mother but not in her 2-year old daughter. Examination of the patient's course provides clues about the latency period and transmission of HTLV-I and highlights similarities between HTLV-I-positive and HTLV-I-negative cutaneous T cell lymphoma. PMID- 2890675 TI - CT appearance of liver metastases from medullary carcinoma of the thyroid. PMID- 2890676 TI - Benzodiazepine dependence. AB - Benzodiazepines (BDPs) are widely used drugs that are effective in controlling the symptoms of anxiety. Tolerance develops rapidly to some of the effects but not to anxiolytic effect in most patients. Dependence occurs at usual therapeutic doses and in a small proportion of patients is accompanied by an enormous increase in the dose taken. The majority of subjects using very high doses are dependent on other substances concurrently. On discontinuing BDPs patients may suffer from relapse of the original condition, rebound in the severity of the symptoms of the original condition or the onset of new symptoms in an abstinence syndrome. If BDPs are discontinued abruptly there may be severe consequences such as seizures. With tapering of the dose, even if this is rapid and from high dose, high potency BDP, the subject will probably experience considerable discomfort but rarely life-threatening effects. Whilst there is concern that BDPs are used too freely, the conditions treated are accompanied by significant morbidity and mortality. The prevalence of pure BDP dependence is low and it is still a matter of debate as to how often BDPs should be prescribed, for which conditions and for what length of time. PMID- 2890677 TI - Beta-blockers in anxiety disorders. AB - Studies evaluating the antianxiety and antipanic properties of beta-blockers do not support their routine use in treating either generalized anxiety disorder or panic disorder. The use of propranolol for anxiety disorders accompanied by physical symptoms, especially cardiovascular complaints, may be effective in some patients when combined with benzodiazepines or perhaps in some non-responders to conventional treatment. Better designed studies are needed to evaluate the exact role of beta-blocking agents in treating anxiety. The efficacy of propranolol in patients with panic disorder has not been widely researched, but preliminary results have not been encouraging. Propranolol may provide symptomatic relief in some patients with residual somatic complaints (i.e., palpitations and tachycardia), when combined with the patient's ongoing drug regimen. Because beta blockers may induce depression, they should be used cautiously--if at all--in panic patients with concurrent depressive illness. PMID- 2890678 TI - Benzodiazepines in panic disorder and agoraphobia. AB - Benzodiazepines, particularly alprazolam, are quickly becoming the drugs of first choice in the treatment of many cases of panic and agoraphobia. The reason for this choice is that these drugs are safer to use, quicker in onset of action, easier for the physician to prescribe and more pleasant for the patient to take than the alternatives. Although the treatment of panic disorder and agoraphobia has been best studied with the benzodiazepine alprazolam, it now appears likely that other benzodiazepines, for example diazepam, lorazepam and chlorazepam, may also be effective when correctly used. There is no reason at this point to believe that any of the benzodiazepines are unique in this regard. Future research will undoubtedly clarify this observation. In the meantime, it is hoped that some of the guidelines in this paper will help the practicing clinician in the management of his patient with this disabling and neglected disease. PMID- 2890679 TI - Drug treatment of social phobia. AB - Social phobia is a potentially serious anxiety disorder that has attracted research interest in the U.S.A. very recently. Patients with social phobia suffer severe anxiety only in the context of social situations. Men are more likely to be afflicted than women. Alcohol and drug abuse are frequent complications. Two classes of medication are promising in treating this condition--beta-adrenergic receptor blockers and monoamine oxidase inhibitors. Data supporting the use of these drugs are reviewed and recommendations for pharmacologic management of social phobics are outlined. PMID- 2890680 TI - Drug treatment of anxiety disorders: update 1987. PMID- 2890681 TI - Benzodiazepines: selective administration. AB - Benzodiazepines are unique chemicals with anxiolytic, anticonvulsant, muscle relaxant and hypnotic properties. Twelve preparations of this group are available in the U.S.A.: two of them belong to the triazolo and one to the 3-nitro groups, the remaining ones are 3-OH or 2-keto benzodiazepines. A number of commonly employed drugs interact with benzodiazepines. Benzodiazepine receptor antagonists which block only one of its actions have been isolated. These promise to lead to preparations with only anxiolytic action without sedation or anticonvulsant action in the future. Guidelines for the selection of the proper drug and for the prevention of dependence are described. PMID- 2890682 TI - Effects of beta-adrenergic and calcium antagonists on the development of anaphylactoid reactions from radiographic contrast media during cardiac angiography. AB - Anaphylactoid reactions (ARs) occurring in patients receiving propranolol have been described as unusually severe and having a "sluggish" response to epinephrine. Although the mechanism of ARs to iodinated radiographic contrast media is not IgE mediated, because of widespread use of beta-adrenergic blocking agents, we undertook a prospective study to determine the incidence of AR to radiographic contrast media during cardiac angiography. Nine hundred fifty-two consecutive patients were divided into four groups according to concomitant chronic medications. Group I (447 patients) were receiving no beta-adrenergic blocking agents or calcium antagonists. Group II (216 patients) were receiving a beta-adrenergic blocking agent. Group III (147 patients) were receiving a calcium antagonist but not a beta-adrenergic blocking agent. Group IV (142 patients) were receiving both a calcium antagonist and a beta-adrenergic blocking agent. The reaction rates, respectively, in the four groups were 4.47%, 7.41%, 5.44%, and 4.93%. The rates of ARs were not associated with the use of concomitant medications in any of the groups (chi 2 = 2.531; p = 0.47). The probability of a type II error in comparison of groups I and II was 0.75 should the true incidence of reactions in patients receiving beta-adrenergic antagonists be 7.41%. No difference in the incidence of AR was observed between patients taking selective and nonselective beta-adrenergic blocking agents in group II. Specific ARs occurring in patients receiving beta-adrenergic blocking agents were usually mild and often without need for specific pharmacotherapy. PMID- 2890683 TI - Clonidine-induced suppression of plasma catecholamines in states of adrenal medulla hyperfunction. AB - To assess adrenal medulla activity in states of hyperfunction, a single 0.3 mg oral dose of clonidine hydrochloride (Catapres) was given to twelve patients with varying evidence of familial adrenal medullary hyperplasia and pheochromocytomas from kindreds with Multiple Endocrine Neoplasia type 2 syndrome (MEN-2), seven patients with sporadic pheochromocytomas and six normal subjects. Mean arterial blood pressure and plasma norepinephrine (NE) levels were lower than baseline values 2 h after clonidine in the normal subjects. Plasma epinephrine (E) rose in one normal but fell in the remainder after clonidine administration. In sporadic pheochromocytoma patients, E fell slightly in 4 and NE fell in 3 while mean arterial blood pressure was not significantly lower than baseline values in 7 patients 2 h after clonidine. In MEN-2, mean arterial blood pressure fell and there was a variable response of plasma E and NE to clonidine, which appears to be related to the presence of detectable anatomic (CT scan) and functional (131I mlBG scintigraphy) abnormalities of the adrenal medulla. These findings are thus compatible with the spectrum of adrenal medulla dysfunction and the presumed development of pheochromocytoma in this syndrome. PMID- 2890685 TI - Percutaneous treatment of an intrahepatic abscess caused by a penetrating duodenal ulcer. AB - We present a well-documented case of duodenal ulcer that penetrated into the quadrate lobe of the liver with subsequent abscess and fistula formation. An accurate diagnosis depended on the use of ultrasound to identify the presence of an abnormal gas pattern in the liver which had been mistaken for bowel on computed tomography. Successful percutaneous drainage under ultrasound guidance was then accomplished. This is the first recorded case we can find in which percutaneous drainage combined with antibiotic and H2 blocker therapy was able to supplant the surgical treatment of liver abscess with an enteric fistula. The diagnosis and management of this condition are discussed. Special reference is made to the use of ultrasound to overcome a major pitfall in the use of computed tomography for diagnosing liver abscesses with fistula formation. PMID- 2890684 TI - Usefulness of basal catecholamine plasma levels and clonidine suppression test in the diagnosis of pheochromocytoma. AB - In the present paper we report our experience on the utility of basal plasma catecholamine (CA) measurement and of the clonidine-suppression test in the diagnosis of pheochromocytoma. Basal noradrenaline (NA) and adrenaline (A) were assayed in plasma samples of 27 subjects affected by pheochromocytoma. When compared to basal values obtained in hypertensive patients without pheochromocytoma, one or both the CA resulted pathologically elevated in all patients except one. The response to the clonidine-suppression test was evaluated in 41 hypertensive patients suspected of having a pheochromocytoma measuring plasma NA and A in basal conditions and 2 and 3 h after oral administration of 300 micrograms clonidine. Extensive laboratory and instrumental findings confirmed the presence of pheochromocytoma only in 12 patients. Among the other 29 patients basal plasma CA resulted higher than normal in 4 patients. In patients without pheochromocytoma clonidine induced a significant fall in both NA and A plasma levels. The decrease in NA was observed in each patient. The 12 patients with pheochromocytoma showed a pathological elevation of one or both the CA. In this group clonidine did not significantly suppress plasma CA. The individual responses were extremely variable. Our data confirm the validity of plasma CA measurement as a diagnostic tool for the diagnosis of pheochromocytoma. The results of the clonidine-suppression test were generally confirmatory of the basal CA plasma values but in the 4 hypertensive patients without pheochromocytoma who showed basal plasma CA higher than normal clonidine resulted a useful tool in excluding the presence of pheochromocytoma. PMID- 2890686 TI - Immunocytochemical localization of P170 at the plasma membrane of multidrug resistant human cells. AB - P170 (P-glycoprotein) is a membrane protein found in high levels in multidrug resistant cultured cell lines. We have localized this protein using monoclonal antibody MRK16 by immunofluorescence and electron microscopy in the multidrug resistant human carcinoma cell line KB-C4. The P170 determinant recognized by antibody MRK16 was found on drug-resistant KB-C4 cells, but not on parental drug sensitive KB-3-1 cells. The determinant was present on the external surface of the plasma membrane and on the luminal side of Golgi stack membranes. P170 was excluded from coated pits at the plasma membrane and absent from endocytic vesicles and lysosomes. This determinant was detected only in small amounts in the endoplasmic reticulum. The high protein concentration of P170 in the plasma membrane is consistent with a role of this protein as a drug efflux pump at the cell surface. PMID- 2890687 TI - Beta-adrenergic-receptor-mediated suppression of interleukin 2 receptors in human lymphocytes. AB - Adrenergic receptor agonists are known to attenuate the proliferative response of human lymphocytes after activation; however, their mechanism of action is unknown. Since expression of interleukin 2 (IL-2) receptors is a prerequisite for proliferation, the effect of beta-adrenergic receptor agonists on lymphocyte IL-2 receptors was studied on both mitogen-stimulated lymphocytes and IL-2-dependent T lymphocyte cell lines. In both cell types the beta-adrenergic receptor agonist isoproterenol blocked the expression of IL-2 receptors, as determined with the IL 2 receptor anti-TAC antibody. To determine the effect of beta-adrenergic agonists on expression of the high affinity IL-2 receptors, [125I]IL-2 binding studies were performed at concentrations selective for high affinity sites. No significant effect of beta-adrenergic agonists on high affinity IL-2 receptor sites could be detected. The data demonstrate that beta-adrenergic receptor agonists down-regulate IL-2 receptors primarily affecting low affinity sites. PMID- 2890688 TI - Mapping of C2, Bf, and C4 genes to the swine major histocompatibility complex (swine leukocyte antigen). AB - Three miniature swine lines, inbred for swine leukocyte antigen (SLA) haplotypes, a, c, and d, and a recombinant line, haplotype g, were analyzed for possible restriction fragment length polymorphisms (RFLP) by Southern blot hybridization with human C2, factor B (Bf), and C4 specific probes. The search for RFLP by using a human C2 probe failed to reveal any variants. However, a Taq I polymorphism was identified with the human Bf probe and Bam HI and Pvu II polymorphisms were identified with the human C4 probe. Overlapping restriction fragments were found with the C2 and Bf probes, which strongly suggests close linkage of C2 and Bf genes in swine. Segregation analyses of the Bf and C4 polymorphisms indicated that the polymorphic fragments followed a Mendelian pattern of inheritance. The recombinant haplotype g, which expresses class I genes of haplotype c and class II genes of haplotype d, was shown to produce an identical RFLP pattern, by using the Bf and C4 probes, as haplotype d, but different from that of haplotype c. This indicates that there is a close association of [C4-Bf-C2] and class II genes in miniature swine. Although these data do not show conclusively the location of the [C4-Bf-C2] genes, it is hypothesized that swine [C4-Bf-C2] genes are located between the class II and class I genes, as has been demonstrated in mouse and man. PMID- 2890689 TI - Molecular variation of human major histocompatibility complex DQw3 beta-chains. AB - Histocompatibility leukocyte antigen DQ molecules exhibit polymorphism of both DQ alpha- and beta-chains. Histocompatibility leukocyte antigen-DQw3 is associated with both DR4 and DR5 and can be further subdivided by reactivity with the monoclonal antibody TA10. To determine the molecular nature of the DQ polymorphic alleles associated with the DR4 haplotype, we have sequenced and analyzed DQ alpha and beta cDNA clones obtained from a DR4, Dw4, DQw3 cell line which is TA10 positive. The DQ alpha-chain sequence was identical to previously published sequences from the DR4 haplotype, but the DQ beta sequence differed from published DR4-DQ beta sequences obtained from DQw3-positive TA10-negative cell lines by eight amino acids, six of which were located in the beta 1 domain. Thus, the TA10 serologic determinants reside on the DQ beta-chain. A TA10-specific oligonucleotide probe was constructed based on the DQ beta sequence, and its specificity was confirmed in a panel of TA10-positive and TA10-negative cell lines. An additional band was observed in Southern blotting experiments which may indicate a donor sequence for gene conversion. PMID- 2890690 TI - Isolation of a hantavirus from a severely ill patient with hemorrhagic fever with renal syndrome in Greece. PMID- 2890691 TI - Hemorrhagic fever with renal syndrome: report of a case in Malaysia. PMID- 2890692 TI - A morphometric study of coated pit formation on the subplasmalemmal surface of murine peritoneal macrophages after adhesion to glass. AB - Murine peritoneal macrophages were settled onto treated and untreated glass at 4 degrees C. The cells were warmed to 37 degrees C and at different time intervals, after being briefly in buffer containing 1 mM ZnCl2, they were subjected to a stream of buffer regulated by a peristaltic pump. By controlling the time of extraction with the buffer stream, it was possible to remove all attached cytoskeletal filaments and relatively clean preparations of the subplasmalemmal surface could be obtained. Platinum replicas of the remaining ventral subplasmalemmal surfaces were prepared and examined by transmission electron microscopy and the extent of clathrin pit formation was assessed morphometrically. It was found that clathrin-coated pits and vesicles formed on untreated or positively charged glass surfaces after only 2 min at 37 degrees C, reaching a peak in 2 hr, when approximately 5% of the available surface was occupied by these structures. The proportion of plasmalemma occupied by coated pits was higher on the ventral membranes of resident macrophages settled onto glass surfaces treated with BSA/anti-BSA (greater than 10% of the total substratum-attached membrane). There was no demonstrable difference in the extent of clathrin-coated pit formation between resident and exudate macrophages. PMID- 2890694 TI - Atypical acinar cell lesions of the pancreas in mice induced by 4 hydroxyaminoquinoline-1-oxide. AB - The carcinogenic effect of 4-hydroxyaminoquinoline-1-oxide (4-HAQO) on exocrine pancreas of mice after a single intravenous (i.v.) injection was investigated. At a dose of 24 mg/kg body weight, 100% of the mice killed at the end of 40 weeks had developed atypical acinar cell foci (AAF) in the pancreas. Each pancreas contained an average of 18.3 +/- 2.7 AAF. Cells in AAF were arranged as acini and their cytoplasm contained eosinophilic zymogen granules. The nuclei were large, round to oval, basally located and contained 1-2 prominent nucleoli. Cells in AAF showed a markedly increased mitotic activity with an index of 4 +/- 0.7/1000 cells as compared to a value of 0.25 +/- 0.25 in the acinar cell population of control pancreas. Autoradiographic studies showed a labeling index of 23 +/- 3 in AAF as compared to only 1.5 +/- 0.29 in the pancreatic acinar cells of controls. These findings indicate that 4-HAQO induces pancreatic lesions in mice which are quite similar to the acidophilic foci observed in rat pancreas and may serve as another useful model for studies of pancreatic carcinogenesis. PMID- 2890693 TI - Pancreatic hormones in streptozotocin-diabetic rats. AB - Pancreatic polypeptide (PP) levels of plasma and pancreas were studied in the rat after streptozotocin (STZ) injection. In 4 weeks of observation, plasma PP was elevated up to 4 times the control values with marked hyperglycemia and insulinopenia. At 4 weeks, intravenous (i.v.) glucose tolerance tests and i.v. insulin tolerance tests were performed. In the glucose tolerance test, control rats responded with a 10-fold increase in plasma insulin and 15% decrease in plasma PP levels, whereas STZ-diabetic rats produced no increase of plasma insulin and an approximately 50% reduction of plasma PP levels with marked hyperglycemia. In the insulin tolerance test, diabetic rats showed a marked increase in plasma PP levels and less increase in plasma insulin levels than the controls. In diabetic rats, pancreatic insulin levels were reduced to about 3.5% of control, whereas those of somatostatin (SRIF), PP and glucagon were elevated to 8.3, 2.7 and 1.4 times control, respectively. In a morphometric study, islet areas of diabetic rats were seen to be reduced to about 10% of control. With in vitro perfused pancreatic slices, STZ-diabetic pancreas released much more glucagon and PP than control pancreas. Thus, STZ injection in the rat caused marked beta-cell damage as well as hyperplasia of SRIF, PP and glucagon cells, with glucagon and PP hypersecretion. PMID- 2890695 TI - Role of secretin and CCK in the stimulation of pancreatic secretion in conscious dogs. Effects of atropine and somatostatin. AB - The role of gut hormones, such as secretin and CCK, in the stimulation of pancreatic secretion by duodenal HCl or oleate and by meat feeding has been studied in conscious dogs before and after pretreatment with atropine and somatostatin. Plasma hormones were measured by specific and sensitive radioimmunoassays. Duodenal perfusion with HCl and oleate stimulated dose dependently pancreatic HCO3 and protein secretion and raised plasma levels of secretin and CCK, respectively. Atropine reduced significantly both HCO3 and protein secretion but did not affect plasma secretin and CCK levels in these studies. Both exocrine pancreatic secretion and plasma secretin and CCK levels were suppressed by somatostatin. Meat feeding caused a marked pancreatic HCO3 and protein secretion accompanied by a significant increase in plasma secretin and CCK which seem to play an important role in the postprandial pancreatic stimulation. Both atropine and somatostatin reduced the pancreatic secretion induced by exogenous hormones but only somatostatin, but not atropine, significantly decreased plasma secretin and CCK responses to intestinal stimulants. We conclude that both atropine and somatostatin reduce the pancreatic responses to duodenal HCl or oleate or to meat feeding but only somatostatin is capable of suppressing the release of secretin and CCK. PMID- 2890696 TI - [An epidemiologic study on rats associated with outbreak of hemorrhagic fever with renal syndrome--comparison with antibodies for two virus strain, Hantaan virus 76-118 strain and newly isolated WKM strain]. PMID- 2890697 TI - [An epidemiologic study on HFRS after six years surveillance--comparison with antibodies for two virus strain, Hantaan virus 76-118 strain and WKM strain in members of college]. PMID- 2890699 TI - [QT prolongation syndrome]. PMID- 2890698 TI - Immunological concepts in insulin-dependent (type I) diabetes mellitus. PMID- 2890700 TI - [A case of neuroleptic malignant syndrome associated with myoglobinuric acute renal failure]. PMID- 2890701 TI - Influence of factor XIII and fibronectin on fiber size and density in thrombin induced fibrin gels. AB - The possible role of fibronectin as a molecular anchor for fibrin to ground substance, the ability of factor XIII to cross-link fibronectin to fibrin, and the demonstrated differences between purified fibrin and fibrin formed in plasma prompted this study of the effect of both proteins on fibrin assembly and structure. The influences of activated factor XIII (FXIIIa) and fibronectin were studied by use of turbidity techniques. Fibronectin over a concentration range of 0 to 800 micrograms/ml produced no change in either the mass-length ratio or density of fibrin fibers in 1 mg/ml fibrin gels. FXIIIa at concentrations as high as 6.5 mumol/L, although not altering fiber mass-length ratio, caused a 30% increase in fiber density. Gels formed in the presence of fibronectin plus FXIIIa demonstrated increasing fiber mass-length ratios and increasing fiber density with increasing fibronectin concentration. Mass-length ratios for gels formed in the presence of 3.24 mumol/L FXIIIa increased from 3.25 to 5.20 x 10(13) daltons/cm as the fibronectin concentration increased from 0 to 800 micrograms/ml. Fiber density increased from 13.6 to 19.1 x 10(22) daltons/cm3 over the same fibronectin range. These results imply that FXIIIa-induced structural changes such as increased elastic modulus may be mediated in part by increased fiber density. Fibronectin alone has virtually no impact on fibrin assembly, but in the presence of FXIIIa becomes incorporated into fibrin and results in increased fiber size and density. PMID- 2890702 TI - Uricoteley:its nature and origin during the evolution of tetrapod vertebrates. AB - The hepatic mechanism for detoxication of ammonia formed during amino acid gluconeogenesis in uricotelic vertebrates requires the intramitochondrial synthesis of glutamine by glutamine synthetase. This glutamine then serves as a precursor of uric acid in the cytosol. The evolutionary development of uricoteley thus required the localization of glutamine synthetase in liver mitochondria. The mechanism for the mitochondrial import of glutamine synthetase in uricotelic vertebrate liver is not yet known. Tortoises, extant relatives of the stem reptiles, possess both the ureotelic and uricotelic hepatic systems. It therefore seems likely that the genetic events allowing the mitochondrial localization of glutamine synthetase in liver occurred in the amniote amphibian ancestors of the stem reptiles. The selection of ureoteley by the theropsids and of uricoteley by the sauropsids were major events in the divergence and subsequent evolution of these two lines. Once established in the sauropsid line, uricoteley has persisted through to the higher reptiles, crocodilians, and birds. Uricoteley was in part responsible for the radiation of the archosaurs during the Triassic as a water conserving mechanism in the adult, thereby allowing them to invade the arid environments of that period. Contrary to dogma, uricoteley was probably of minor significance in the development of the cleidoic egg. Neither mammalian nor avian embryonic liver tissues catabolize amino acids to any great extent, so it is inappropriate to attribute to them a kind of "waste" nitrogen metabolism. PMID- 2890703 TI - Isolation frequency and growth properties of HIV-variants: multiple simultaneous variants in a patient demonstrated by molecular cloning. AB - The biological properties and efficiency of isolation of different HIV (LAV/HTLV III, ARV, and AAV) subtypes were evaluated by recovering and growing HIV on fresh peripheral human lymphocytes. Cultures for virus isolation were performed from more than 180 German AIDS, ARC, LAS, and virus-exposed asymptomatic patients. The virus isolation rate depended on the state of health of the patients being close to 80% in AIDS patients, 30-40% in ARC/LAS patients, and lower in asymptomatic HIV seropositive patients. The cytopathic effects of the HIV isolates obtained on lymphocyte-cell cultures ranged from no effect to marked syncytia formation and cytopathogenicity. Marked differences were also observed in the replication rate of the various isolates. These properties were stable in all in vitro passages of the viruses performed so far and allowed to tentatively define four subtypes of HIV. In the majority of AIDS cases with neurological symptoms well-growing strains were obtained from peripheral blood, while all but two isolates from the cerebrospinal fluid of the same patients grew remarkably slowly and to only low titres on lymphocytes, suggesting that selection of variants for growth at specific sites of the body occurs. For one of the most cytopathogenic strains the influence of several variables of culture conditions (cell type, corticosteroids, IL-2, and polybrene) on virus replication was studied. Apart from polybrene, all parameters strongly influenced replication. PMID- 2890704 TI - Spread of human T-cell leukemia virus (HTLV-I) in the Dutch homosexual community. AB - Sequential sera of 697 homosexual men, participating in a prospective study (1984 1986) of the risk to acquire human immunodeficiency virus (HIV) or AIDS, were tested for antibodies to human T-cell leukaemia virus (HTLV-I) by particle agglutination and immunoblotting. No intravenous drug users were included in this trial. Three men (0.4%) were HTLV-I antibody positive at intake and an additional 2 at the end of the observation period, resulting in an attack rate of approximately 0.3%. One of the 3 men with HTLV-I antibodies at intake was a Brazilian. One man had an acute HTLV-I infection after sexual intercourse with a Brazilian during holiday in Brazil. No serological cross-reactivity with HIV was observed nor a relationship with other sexually transmissible viral or bacterial infections. In contrast to HIV no relationship with anogenital intercourse was noted; both primary HTLV-I infected men practiced only orogenital intercourse. This suggests that HTLV-I was imported in the Dutch homosexual community after HIV was introduced in the Netherlands. HTLV-I appears to spread slower within the homosexual community than HIV and possibly by other routes. PMID- 2890705 TI - Cytomegalovirus infections in adult T-cell leukemia patients. AB - Cytomegalovirus (CMV) infection frequently occurred in patients with malignant lymphoma of T-cell origin, especially with adult T-cell leukemia (ATL). This was evidenced by histopathological examination at autopsy, isolation of CMV, and detection of CMV antibodies that indicate recent or active infection. Cellular immune response was suppressed in most ATL patients when examined by skin hypersensitivity reaction to purified protein derivatives (PPD), streptococcal antigens (SuPs), and phytohaemoagglutinin (PHA). None of the CMV-positive patients reacted to them. Thus, the presence of tumor cells of T-cell origin and the absence of skin hypersensitivity reaction seem to be risk factors for CMV infection. Each CMV isolate exhibited unique DNA fingerprints, suggesting that cross-infection of CMV did not occur among the ATL patients on the same ward. PMID- 2890706 TI - The characterization of the dopaminergic profile of EMD 23,448, and indolyl-3 butylamine: selective actions on presynaptic and supersensitive postsynaptic DA receptor populations. AB - The effects of the dopamine (DA) agonist EMD 23,448 on central normosensitive and supersensitive DA receptors were investigated. EMD 23,448 only slightly inhibits rat striatal DOPA synthesis in vivo and does not inhibit the enhanced striatal DOPA synthesis elicited by acute administration of haloperidol. Also unlike other DA agonists it does not increase striatal acetylcholine levels. However, it inhibits striatal DOPA synthesis in rats with DA receptors rendered supersensitive by chronic treatment with haloperidol. EMD 23,448 also effectively inhibits the enhanced striatal DOPA synthesis elicited by administration of GBL. Furthermore, EMD 23,448 selectively reduces, in a dose-dependant way, DA utilization in nerve terminals of the central caudate and in dotted terminals of the ventral striatum but DA utilization in the substantia nigra is unaffected. The most marked reduction of DA utilization was induced in the anteromedial frontal cortex. These results indicate that EMD 23,448 selectively stimulates presynaptic DA receptors and supersensitive postsynaptic DA receptors. Behavioral experiments in animals with normosensitive and supersensitive DA receptors also indicate that EMD 23,448 effectively stimulates presynaptic and supersensitive postsynaptic DA receptors. Receptor binding studies have shown that EMD 23,448 has a high affinity for the D2 DA receptors, but it ineffectively promotes the coupling of the DA receptors with the guanine nucleotide regulatory protein. However, at supersensitive striatal DA receptors the coupling is shown to be enhanced by EMD 23,448. The selectivity of EMD 23,448 for presynaptic DA receptors might, at least in part, be related to the presence of DA receptor reserves which are sensitive to EMD 23,448. With regard to the selectivity of EMD 23,448 for supersensitive postsynaptic DA receptors an increase in the efficiency of the coupling mechanism upon activation by EMD 23,448 is probably involved. PMID- 2890707 TI - Sleep and benzodiazepine receptor sub-types. AB - CL 218,872, which preferentially binds to benzodiazepine (BZ) type 1 receptors, and flurazepam, which is thought to bind to both types 1 and 2, were given alone and in combination to rats. CL 218,872 had little effect on sleep latency, but significantly increased total sleep time. As expected, flurazepam both shortened sleep latency and prolonged total sleep. Pretreatment with CL 218,872 had no effect on these alterations in sleep induced by flurazepam. The implications for possible significance of sub-typing of BZ receptors are discussed. PMID- 2890708 TI - Search for the familial Alzheimer's disease gene. AB - The application of molecular genetic techniques to the study of autosomal dominantly inherited Familial Alzheimer's Disease may provide a means to determine the chromosomal location of the defective gene causing this form of Alzheimer's disease. Knowledge of the chromosomal location of the defective gene will provide a basis for isolating and characterizing this gene. Preliminary investigations indicate that several candidate genes can be excluded as the site of the defect. Current data also indicate that the defective gene does not reside close to random DNA markers on the distal portion of chromosome 21. Additional DNA markers on the proximal portion of chromosome 21 long arm are currently being investigated. PMID- 2890709 TI - Intracerebroventricular cholinergic drug administration in Alzheimer's disease: preliminary results of a double-blind study. AB - In June 1983, we began evaluating intracerebroventricular (ICV) cholinergic drug infusion in patients with biopsy-documented Alzheimer's disease (AD). An initial trial in four patients showed this treatment approach to be feasible, but objective improvement in cognitive or social function was not documented (Harbaugh et al., 1984; Harbaugh, 1986). A double-blind, placebo-controlled crossover study involving a larger number of patients has since been done. The results of this study, presented here, document a statistically significant improvement in some cognitive test results during periods of drug infusion. However, the clinical applicability of this treatment approach is still questionable. A collaborative, double-blind study evaluating activities of daily living and cognitive test results during drug and placebo infusion is presently underway and should better define the safety and efficacy of this treatment approach for patients with AD. PMID- 2890710 TI - Dementing conditions studied with PET. AB - Papers published between 1980 and 1986 reporting PET scans performed on patients with dementia are reviewed. Application of PET in clinical practice is limited to date. However, PET methods contribute to clarify pathophysiology of the dementias. Some possibilities for future investigations are outlined but progress will be slow due to the complexities of the technique. PMID- 2890711 TI - Isolated brain microvessels as in vitro equivalents of the blood-brain barrier: selective removal by collagenase of the A-system of neutral amino acid transport. AB - On treatment with collagenase, brain microvessels, together with several protein components, lose some enzymatic activities such as alkaline phosphatase and gamma glutamyltranspeptidase, whereas no change occurs in the activities of 5' nucleotidase and glutamine synthetase. The energy-requiring "A-system" of polar neutral amino acid transport is also severely inactivated, whereas the L-system for the facilitated exchange of branched chain and aromatic amino acids is preserved. In the collagenase-digested microvessels, this leads to loss of the transtimulation effect of glutamine on the transport of large neutral amino acids, because such transtimulation is due to a cooperation between the A- and L systems. By contrast, NH4+ maintains (and even enhances) its ability to stimulate the L-system of amino acid transport, presumably through glutamine synthesis within the endothelial cells. PMID- 2890713 TI - A micromethod for the isolation of large and small microvessels from frozen autopsied human brain. AB - Microvessels were isolated from autopsied human brain using a simple procedure involving disruption, sieving, and centrifugation on a sucrose density gradient. The present procedure is characterized by isolation, from frozen autopsied brain, of materials either from the cerebral cortex or white matter, and subsequent separation of the capillary fraction from the large vessel fraction. The preparation appears highly purified under phase-contrast microscopic examination. The purity was also established by the enrichment of gamma-glutamyl transpeptidase activity and by the nearly negligible cerebroside content in the vessel fractions as compared to the brain homogenate. PMID- 2890712 TI - Intracellular pH and catecholamine synthesis in cultured bovine adrenal medullary cells: effect of extracellular Na+ removal. AB - Incubation of cultured bovine adrenal medullary cells in Na+-free sucrose medium or in Na+-free Cs+ medium enhanced the synthesis of 14C-catecholamines from [14C]tyrosine about two- to threefold or sixfold, respectively. The increment of 14C-catecholamine synthesis produced by Na+-free medium was partially dependent on the presence of Ca2+ in the medium. Dibutyryl cyclic AMP also stimulated the synthesis of 14C-catecholamines in adrenal medullary cells, and the effects of Na+ removal and dibutyryl cyclic AMP (5 mM) on the synthesis were almost additive. The intracellular pH measured by using a weak acid 5,5 dimethyloxazolidine-2,4-dione was 7.14 in control cells and when Na+ was replaced by sucrose or Cs+, it shifted down to 6.56 or 5.66, respectively. The fall in intracellular pH and the stimulation of 14C-catecholamine synthesis were similarly dependent on the concentration of Na+ in the medium. The optimal pH of soluble tyrosine hydroxylase was 5.5-6.0 both in control cells and in cells incubated in Na+-free medium. These results suggest that removal of extracellular Na+ increases the synthesis of catecholamines, at least in part, by shifting the intracellular pH toward the optimal pH of tyrosine hydroxylase. PMID- 2890714 TI - Glutamate receptor subtypes in cultured cerebellar neurons: modulation of glutamate and gamma-aminobutyric acid release. AB - Using cerebellar, neuron-enriched primary cultures, we have studied the glutamate receptor subtypes coupled to neurotransmitter amino acid release. Acute exposure of the cultures to micromolar concentrations of kainate and quisqualate stimulated D-[3H]aspartate release, whereas N-methyl-D-aspartate, as well as dihydrokainic acid, were ineffective. The effect of kainic acid was concentration dependent in the concentration range of 20-100 microM. Quisqualic acid was effective at lower concentrations, with maximal releasing activity at about 50 microM. Kainate and dihydrokainate (20-100 microM) inhibited the initial rate of D-[3H]aspartate uptake into cultured granule cells, whereas quisqualate and N methyl-DL-aspartate were ineffective. D-[3H]Aspartate uptake into confluent cerebellar astrocyte cultures was not affected by kainic acid. The stimulatory effect of kainic acid on D-[3H]aspartate release was Na+ independent, and partly Ca2+ dependent; the effect of quisqualate was Na+ and Ca2+ independent. Kynurenic acid (50-200 microM) and, to a lesser extent, 2,3-cis-piperidine dicarboxylic acid (100-200 microM) antagonized the stimulatory effect of kainate but not that of quisqualate. Kainic and quisqualic acid (20-100 microM) also stimulated gamma [3H]-aminobutyric acid release from cerebellar cultures, and kynurenic acid antagonized the effect of kainate but not that of quisqualate. In conclusion, kainic acid and quisqualic acid appear to activate two different excitatory amino acid receptor subtypes, both coupled to neurotransmitter amino acid release. Moreover, kainate inhibits D-[3H]aspartate neuronal uptake by interfering with the acidic amino acid high-affinity transport system. PMID- 2890715 TI - Ubiquitin-directed antibodies inhibit neuronal transporters in rat brain synaptosomes. AB - Affinity-purified antibodies specific for ubiquitin were found to inhibit the sodium-dependent uptake of [3H]choline, gamma-[3H]aminobutyric acid [( 3H]GABA), [3H]glutamate, [3H]norepinephrine, [3H]aspartate, and [3H]serotonin in rat cerebral cortical synaptosomes at a low concentration (10 micrograms/ml). These antibodies (termed anti-Ub) had no effect on the sodium-independent uptake of these substances or their calcium-dependent efflux. Synaptosomal [3H]deoxyglucose uptake was not affected in normal Krebs Ringer buffer containing 10 mM glucose, but was inhibited in glucose-free medium. Other nonneuronal sodium-dependent transport processes were found to be unaffected by 10 micrograms/ml anti-Ub, suggesting that anti-Ub does not bind indiscriminantly to sodium-binding sites on sodium-dependent organic solute transporters. Finally, anti-Ub inhibited sodium dependent [3H]GABA and [3H]glutamate uptake in plasma membrane ghosts, devoid of membrane potential, which were derived from rat cerebral cortical synaptosomes. These results suggest that neuronal transporters or sites proximal to them may be ubiquitinylated on the plasma membrane surface. PMID- 2890716 TI - Beta-endorphin, somatostatin, and prolactin levels in cerebrospinal fluid of epileptic patients after generalised convulsion. AB - The possible role of different peptidergic systems in the postictal stage of human epilepsy was studied by measuring beta-endorphin, somatostatin, and prolactin levels by radioimmunoassay of cerebrospinal fluid (CSF) from nine epileptic patients. The first sample was taken within 2 hours after generalised tonic-clonic convulsion, and the second sample was obtained interictally after 1 4 days without any kind of clinically observable seizures. beta-endorphin was elevated postictally (p = 0.044) compared with interictal levels. SLI and PROL were similar in both samples. The present study suggests that in humans beta endorphin is released into CSF during generalised seizures. This may indicate that neurons containing beta-endorphin are activated during a seizure. PMID- 2890717 TI - Development of the ultrastructural features of somatostatin-immunoreactive neurons in the rat visual cortex. AB - The peroxidase-antiperoxidase immunocytochemical technique has been used to examine the development of the ultrastructural features of somatostatin (SRIF) immunoreactive neurons in the visual cortex of the rat between embryonic day 17 and postnatal day 32. In the adult, stained neurons are distributed in layers II through VI and characterized by an abundance of cytoplasm containing a plethora of organelles, most conspicuous of which are cisternae of granular endoplasmic reticulum organized in parallel arrays. In embryonic tissue, SRIF-positive cells are present in the subplate and in the border between the cortical plate and marginal zone. These cells possess scanty cytoplasm containing a few organelles; synapses onto immunoreactive perikarya and dendrites are evident at this stage. At birth and in early postnatal life, labelled cells are confined to the subplate region. Already at this age a number of cells display signs of ultrastructural features which characterize them in adult life. At the end of the first postnatal week, SRIF-immunoreactive neurons span a considerable spectrum of maturity. At one extreme are a few cells with little cytoplasm surrounding a large nucleus and at the other are the majority of labelled neurons showing abundant cytoplasm including prominent arrays of granular endoplasmic reticulum. Labelled cells first appear in the more superficial layers at the beginning of the second postnatal week and attain a distribution similar to that observed in adult animals at the end of this week. At this time their ultrastructural features closely resemble those of their adult counterparts, and differences in cytoplasmic maturity between superficial and deep labelled cells are not evident. This suggests that the SRIF-producing neurons in the superficial layers begin to express this peptide after they complete their migration and have acquired their morphological features. Maturation proceeds during the third postnatal week; at this stage most cells acquire their mature nuclear and cytoplasmic features and an adult complement of synapses. However, a number of SRIF-immunoreactive cells contain a particularly prominent accumulation of cytoplasmic organelles and appear hypertrophic. PMID- 2890718 TI - Microtubule-mitochondrial associations in regenerating axons after taxol intoxication. AB - Ultrastructural examination of regenerating axons within rat sciatic nerve injected locally with the microtubule assembly-promoting compound, taxol, has revealed the frequent association of microtubules with axoplasmic organelles, in particular mitochondria. This was characterized by the prodigious accumulation of axonal microtubules, some of which became aligned to form multilayered channels within which axoplasmic organelles were sequestered. Between each layer of microtubules forming the walls of these channels, a 5 nm filament, believed to derive from microtubule side-arm material, was present. The findings suggest that these microtubule channels might play a role in mitochondrial traffic across the lesion area. Similar but much less elaborate associations within axons between microtubules and axoplasmic organelles, including mitochondria, have been described previously. Within regenerating axonal sprouts, intermediate filaments were found only at later timepoints when they commonly occurred within the microtubule channels. It is proposed that taxol impedes axonal regrowth at an early stage of cytoskeleton formation and that that the present observations represent drug-induced exaggerations of a normal phenomenon. PMID- 2890720 TI - A new low-molecular-weight component promoting adrenergic development in cultured chick sympathetic neurons. AB - A low-molecular-weight component present in medium conditioned by cultured chick liver cells (LCM) enhances the adrenergic properties of dissociated chick superior cervical ganglion (SCG) neurons in culture (Zurn and Mudry, 1986). This substance cannot replace NGF as a survival, growth, or differentiation factor. However, in the presence of NGF, it stimulates neuronal metabolism and catecholamine (CA), but not ACh production by the SCG neurons. The effect on transmitter production is greater than that on neuronal metabolism. Yet this is not due to an increase in the specific activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in CA synthesis. Interestingly, the effect of LCM on CA and ACh production, but not on neuronal metabolism, is potentiated in the presence of a large excess of NGF. The active component(s) present in LCM has a molecular weight lower than 500 Da and is not inactivated by heat or pronase treatment. So far, none of the small molecules tested (ascorbic acid, pyruvate, glucose, L glutamic acid, glutathione, etc.) were able to mimic the effects of LCM on the SCG neurons. Thus this report describes a novel low-molecular-weight component different from NGF that promotes metabolism and adrenergic development in cultured chick sympathetic neurons. PMID- 2890719 TI - A comparison of computer-controlled versus manual administration of vecuronium in humans. AB - The short elimination half-life of vecuronium suggests it may be delivered more efficiently by continuous infusion than by traditional bolus injections. The objective of this study was to compare manual administration with computer controlled administration. Anesthesia was induced in 22 patients (American Society of Anesthesiologists [ASA] physical status I and II) with fentanyl and sodium thiopental and maintained with halothane and nitrous oxide in oxygen. Neuromuscular function was assessed at the hypothenar eminence and the adductor pollicis (train-of-four stimulation). A bolus of 0.1 mg/kg of vecuronium was given to obtain 100% twitch depression for tracheal intubation. After twitch height returned to 25% of control, relaxation was maintained by traditional bolus injections (group 1, n = 7), manually controlled continuous infusion (group 2, n = 7), or computer-controlled continuous infusion (group 3, n = 8). In all three groups the desired level of relaxation was 90% twitch depression. Variability of relaxation differed significantly among the three groups (group 1: 10.5%, group 2: 12.4%, group 3: 7.1%). Twitch height was more constant with computer control than with either bolus injections or manual infusion (P less than 0.05). There was no statistically significant difference in the drug requirement (group 1: 1.60 microgram/kg/min, group 2: 1.51 microgram/kg/min, group 3: 1.45 microgram/kg/min). Variability in the mechanomyogram (n = 12) was much higher than in the electromyogram (n = 10). Computer-controlled infusion may be a useful adjunct for the anesthesiologist who desires a stable level of patient relaxation when using short-acting, non-depolarizing relaxants. PMID- 2890721 TI - Catecholaminergic properties of cholinergic neurons and synapses in adult rat ciliary ganglion. AB - Parasympathetic neurons of the ciliary ganglion are innervated by preganglionic cholinergic neurons whose cell bodies lie in the brain stem; the ganglion cells in turn provide cholinergic innervation to the intrinsic muscles of the eye. Noradrenergic innervation of the iris is supplied by sympathetic neurons of the superior cervical ganglion. Using immunocytochemical and histochemical techniques, we have examined the ciliary ganglion of adult rats for the expression of cholinergic and noradrenergic properties. As expected, the postganglionic ciliary neurons possessed detectable levels of choline acetyltransferase immunoreactivity (ChAT-IR). Unexpectedly, many ciliary neurons also exhibited immunoreactivity for tyrosine hydroxylase (TH-IR). Some had dopamine beta-hydroxylase-like (DBH-IR) immunoreactivity, but none contained detectable catecholamines, even after treatment with nialamide and L-DOPA. A sparse plexus of fibers exhibiting faint TH-IR was present in the irises of acutely sympathectomized rats. The terminals of preganglionic axons in the ciliary ganglion exhibited not only immunoreactivity for ChAT, but also for TH and contained stores of endogenous catecholamine. Neither ciliary neurons nor their preganglionic innervation accumulated detectable stores of exogenous catecholamines. Rats sympathectomized as neonates by treatment with 6 hydroxydopamine subsequently had a greater proportion of neurons possessing detectable TH-IR in the ciliary ganglion; both the TH-IR perikarya and their axons in the iris were more intensely immunofluorescent. TH-IR was present in the ciliary neuron cell bodies of mouse, guinea pig, and ferret. These species, however, lacked detectable TH-IR or catecholamine stores in preganglionic terminals. These observations indicate that mature, functionally cholinergic neurons from 2 different embryonic origins, postganglionic ciliary neurons derived from the neural crest and preganglionic neurons derived from the neural tube, display several catecholaminergic properties. PMID- 2890722 TI - Alpha-2 adrenergic regulation of melatonin release in chick pineal cell cultures. AB - The chick pineal gland expresses a circadian rhythm of melatonin biosynthesis, with elevated levels at night and low levels during the day. The rhythm of melatonin is regulated both by circadian oscillators located within the gland itself and by adrenergic input from the sympathetic nervous system. Previous work has shown that norepinephrine administration inhibits melatonin biosynthesis, as measured by the activity of the enzyme serotonin N-acetyltransferase. As a first step toward understanding the mechanisms by which norepinephrine regulates melatonin production in the chick pineal, we have identified the adrenergic receptor involved. Dissociated chick pineal cell cultures were prepared and melatonin release was measured on days 5 and 6 of culture using radioimmunoassay. The effects of adrenergic agonists and antagonists on the nocturnal increase of melatonin release during the 12 hr dark portion of a LD12:12 light cycle were determined. Norepinephrine inhibited melatonin release in a dose-dependent manner, with an average EC50 of 19.7 nM +/- 2.23 (SEM). Melatonin release values ranged from 100 to 4% of the level seen in control cultures, depending on the dose of norepinephrine. The physiological response to epinephrine, norepinephrine, and isoproterenol was stereospecific. The (-) stereoisomer was 6, 8, and 37 times more potent than the (+) stereoisomer, respectively. EC50 values (in nM) for adrenergic agonists were as follows: alpha-methyl-(-)-norepinephrine, 2.46; tramazoline, 3.06; guanabenz, 3.31; clonidine, 3.70; oxymetazoline, 4.29; ( )-epinephrine, 7.44; (-)-norepinephrine, 19.7; (-)-isoproterenol, 463; and (-) phenylephrine, 659. Schild analysis was used to determine the relative potency of adrenergic antagonists. pA2 values for adrenergic antagonists were as follows: rauwolscine, 9.55; RX78 1094, 8.32; yohimbine, 8.14; phentolamine, 7.11; prazosin, 5.93; and (-)-propranolol, less than 6. The relative potencies of both adrenergic agonists and antagonists demonstrate that alpha-2 receptors mediate norepinephrine-induced inhibition of melatonin release in chick pineal cell cultures. The identification of alpha-2 receptors in chick pineal cells should aid in our understanding of the biochemical events initiated by receptor activation that regulate melatonin synthesis. PMID- 2890723 TI - Membrane properties and adrenergic responses in locus coeruleus neurons of young rats. AB - Intracellular recordings were made from locus coeruleus neurons in slices taken from rats 8-26 d of age. Neurons from these animals exhibited spontaneous action potentials, which were superimposed on slow (0.3-3 Hz) rhythmic depolarizations. The frequency of these potentials was closely related to the age of the animals from which the slice was taken, the slowest frequencies being observed in tissues from the youngest animals. In adult animals, such rhythmic activity was only rarely observed under normal recording conditions. The rhythmic depolarizations had a slow rate of rise and fall, were 3-15 mV in amplitude, were not affected by tetrodotoxin, and were abolished in solutions that contained elevated magnesium content. When the membrane potential was hyperpolarized by passing current through the recording electrode, the depolarizing rhythmic activity persisted even at very negative potentials (-120 mV). These depolarizations appear to be generated by the inward movement of calcium ions, probably in dendritic regions of the neuron. Superfusion of phenylephrine caused membrane depolarizations, increased the frequency of action potentials and of the slow, rhythmic depolarizations in about 80% of the cells from young rats, whereas it had no effect or a depressant action on cells from adults. Noradrenaline hyperpolarized the cells through an alpha 2-adrenoceptor and abolished the slow depolarizations. In cells from young rats, the hyperpolarization produced by noradrenaline reached a maximum and then declined, such that there was a "sag" in the membrane potential toward the resting potential following the peak of the hyperpolarization. Following the washout of noradrenaline, the membrane potential repolarized before moving toward the resting level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890724 TI - Taxol interferes with the interaction of microtubule-associated proteins with microtubules in cultured neurons. AB - Treatment of neurons with taxol leads to the formation of microtubule bundles in which individual microtubules are much more closely spaced than in untreated neurons (Letourneau and Ressler, 1984). This suggests that taxol interferes with the mechanisms that regulate microtubule spacing in situ. I have determined whether treatment of neurons with taxol alters the composition of their microtubules, reasoning that such alterations may be related to the taxol-induced alterations in microtubule spacing. Cultures of sympathetic neurons were incubated with 35S-methionine and either taxol, podophyllotoxin, a potent microtubule-depolymerizing agent, or dimethyl sulfoxide (DMSO), the solvent for the drugs. The levels of labeled microtubule-associated proteins (MAPs) assembled into microtubules in the various cultures were then assayed biochemically. I focused on 4 MAPs: tau, chartins, MAP-2, and the MAP with a molecular mass of 210,000 Da (210 kDa). In untreated cultures, these MAPs are prominent components of microtubules. The levels of all MAPs, as well as tubulin, in microtubules were greatly reduced in cultures treated with podophyllotoxin, compared to controls. Taxol had varied effects on the interaction of MAPs with microtubules in situ. Microtubules formed in the presence of taxol contained normal or slightly elevated levels of tau and the 210 kDa MAP compared to microtubules in control cultures. In contrast, microtubules formed in the presence of taxol were almost completely devoid of chartin MAPs and MAP-2 compared to controls. These results show that taxol interferes with the interaction of some, but not all, MAPs with microtubules in situ. The altered MAP composition of microtubules in taxol treated neurons may contribute to the abnormal spacing of microtubules seen in such neurons. PMID- 2890725 TI - Phenotypic properties of catecholamine-positive cells that differentiate in avian neural crest cultures. AB - We have investigated several phenotypic features of the catecholamine-positive (CA+) cell population that develops in quail neural crest cultures. The number, spatial distribution, and morphology of CA+ and tyrosine hydroxylase-positive (TH+) cells are similar at all ages examined, suggesting that these 2 cell classes are identical. Neither CA+ nor TH+ cell bodies or processes were stained using antisera that recognize the 70 or 160 kDa subunits of chicken neurofilament protein. Other cell bodies and fibers in the cultures (which were CA- and TH-) were stained with these neurofilament antisera. The uptake and storage of 3H norepinephrine by neural crest cultures containing CA+ cells were inhibited in the presence of desmethylimipramine and by incubation at 0 degrees C, but were unaffected by normetanephrine. Overnight treatment with reserpine eliminated histochemically detectable CA fluorescence from the cultures. Chronic reserpine treatment from day 2 to 7 in vitro prevented the appearance of CA+ cells, while normal numbers of TH+ and somatostatin-like immunoreactive (SLI) cells developed. The number and light-microscopic morphology of the CA+ cells that developed in these cultures were not dramatically altered by either exogenous NGF or 6 hydroxydopamine. Using the method of Grillo et al. (1974), we have demonstrated that the CA+ cells observed in the light microscope corresponded to cells containing abundant cytoplasmic granular vesicles (GV) characteristic of catecholamine storage granules observed in other systems. The GV diameters were quite similar in cells examined after 5, 7, 14, and 21 d in vitro. Most GV were 50-200 nm in diameter and were distributed in a unimodal manner, with the observed modal values in the range of 85-115 nm at the ages examined. The number of GV/micron2 of cytoplasmic area remained quite constant at all ages examined. These data, taken together with other available information, suggest that the CA+ cells that differentiate in our neural crest cultures resemble, in many respects, the small, intensely fluorescent cells found in autonomic ganglia and extra adrenal chromaffin tissue of many species. At present, we do not know if the CA+ cells that differentiate in our neural crest cultures are a stable endpoint of development or whether they are a developmental intermediate in adrenergic differentiation that is normally observed only transiently during the development of avian sympathetic ganglia in vivo, but that can persist under our tissue culture conditions. PMID- 2890726 TI - Quantitative distribution of the glycine receptor in the auditory brain stem of the gerbil. AB - The concentration and relative distribution of glycine receptors were determined for gerbil brain stem auditory nuclei using 3H-strychnine and quantitative autoradiographic techniques. Significant binding was observed in the anteroventral cochlear nucleus, the dorsal cochlear nucleus, the lateral superior olivary nucleus, and the inferior colliculus. A non-uniform distribution of binding was seen in 3 of these nuclei, such that the greatest concentration of glycine receptors was located in the high-frequency regions. An analysis of neuron soma density suggested that the amount of post-synaptic membrane could partially explain the distribution of receptor. PMID- 2890727 TI - Acute alloxan diabetes alters the activity but not the total quantity of acetyl CoA carboxylase in rat liver. AB - Alloxan diabetes has repeatedly been shown to reduce lipogenesis in rat liver concomitant with decreased activity of acetyl CoA carboxylase. This and other observations led to the deduction that insulin is required for the synthesis of acetyl CoA carboxylase even though the actual amount of enzyme was not measured. We have developed methods to determine the quantity of acetyl CoA carboxylase in crude tissue extracts with which we have reexamined the role of insulin in regulating the amount of the enzyme in liver of acute (3-d) alloxan diabetic rats. The results show that although there was a decrease in the quantity of the active cytoplasmic form of acetyl CoA carboxylase in the liver of alloxan diabetic rats, there was a corresponding increase in the quantity of relatively inactive forms of the enzyme associated with mitochondria. Thus, the total amount of enzyme was minimally affected by the diabetic state. Instead, the results indicate that decreased acetyl CoA carboxylase activity in liver of the diabetic rats was attributable to a shift in the subcellular distribution of the enzyme from the active cytoplasmic to inactive mitochondrial forms. We have shown previously that subcellular distribution of the enzyme is dietary dependent. Results of this study implicate insulin in the mobilization and activation of mitochondrial acetyl CoA carboxylase. PMID- 2890729 TI - The occurrence of multiple endocrine neoplasia type IIb, in two children of an affected mother. AB - Two children with multiple endocrine neoplasia syndrome, Type IIb, (MEN IIb), whose natural mother died from complications of general anesthesia, due to undiagnosed bilateral pheochromocytomas, are described. Of particular interest is the fact that the daughter presented with many stigmata of the syndrome, including the typical facies, while her brother had no obvious clinical manifestations of the syndrome. Both children to date have undergone total thyroidectomy, and pathology reports have confirmed the presence of medullary thyroid carcinoma. PMID- 2890728 TI - Aspartame-sweetened beverage: effect on plasma amino acid concentrations in normal adults and adults heterozygous for phenylketonuria. AB - Twelve normal subjects ingested either unsweetened beverage (n = 6) or beverage providing 4 mg/kg body weight as aspartame (APM) (n = 6). Neither beverage had any significant effect on plasma aspartate or phenylalanine concentrations. After this study, eight normal and six obligate phenylketonuric (PKU) heterozygous adults each ingested a 354-mL (12-oz) beverage serving on two occasions in a randomized cross-over design. On one occasion the beverage was not sweetened; on the other occasion, the beverage provided 10 mg APM/kg body weight. Plasma amino acid concentrations were measured throughout the 2-h study period. The addition of 10 mg APM/kg body weight to the beverage had no significant effect on plasma aspartate concentration. APM ingestion increased plasma phenylalanine levels of normal subjects from a mean +/- SD baseline value of 5.09 +/- 0.82 mumol/dL to a high mean value of 6.73 +/- 0.75 mumol/dL. In PKU heterozygous subjects the plasma phenylalanine level increased from a mean +/- SD of 9.04 +/- 1.71 to a high mean value of 12.1 +/- 2.08 mumol/dL. The data indicate ready metabolism of the aspartate and phenylalanine portion of APM when administered at levels likely to be ingested by individuals who drink diet beverages. PMID- 2890730 TI - Behavioral treatment of food refusal in a child with short-gut syndrome. PMID- 2890731 TI - The effect of particle size and concentration on the adhesive characteristics of a model drug-carrier interactive system. AB - The effect of concentration and particle size on the adhesive tendency of drug particles in a model interactive system was investigated using a centrifuge technique. The model interactive system consisted of drug powders adhered to coated glass carrier beads. Adhesion profiles of per cent of drug remaining on the carrier versus the square of the speed of rotation were a logarithmic normal function. Increase in the adherent particle size and concentration decreased the adhesive tendency of all drug powders studied. Particle collisions during detachment and the formation of multiparticulate layers even before the monolayer saturation of the carrier surface were responsible for the reduced adhesive stability of the drugs on the carrier as the particle loading increased. PMID- 2890732 TI - Experimental investigation of adhesion between powders and surfaces. AB - The adhesion between two pharmaceutical powders (poly (ethylene glycol) 4000 and Sta-Rx 1500) and various metal and polymer substrates has been investigated. The powders were either deposited on the substrates with negligible force or forced on by spinning in a centrifuge. The force required to remove the particles was then evaluated by spinning the substrate-powder samples in a centrifuge and counting the remaining powder after rotation at various speeds. The median adhesive force between the powders and various substrates was similar in the case of particles deposited with negligible force, with the exception of adhesion to PTFE, which was about one-third of the force. After the powders had been forced on to the substrate surface the median adhesive force increased. This increase was approximately five-fold for the Sta-Rx 1500 and up to thirty-fold for the PEG 4000. Differences in the adhesion between each powder and the various substrates were now evident with, for example, Sta-Rx 1500 adhering to stainless steel with a force of 1510 X 10(-9) N, but to Dural with a force of 2380 X 10(-9) N. PMID- 2890733 TI - Antimicrobial activity of n-alkyltrimethylammonium bromides: influence of specific growth rate and nutrient limitation. AB - The antimicrobial activity of an homologous series of n-alkyltrimethylammonium bromides has been assessed towards Escherichia coli grown at a variety of specific growth rates and under various conditions of nutrient limitation. For each individual set of growth conditions activity was parabolically related to the n-alkyl chain length of the compounds and thus to compound lipophilicity (log P). The compound that showed optimal activity and thereby optimal lipophilicity (log Po) changed according to growth rate and nutrient limitation. Such changes are related to variations in the gross cell envelope composition of the cultures (phospholipid, lipopolysaccharide, neutral lipids, proteins). The data therefore support the hypothesis that changes in growth rate and nutrient limitation alter the overall lipophilicity of the cell envelope and thereby the optimal value of log P for compounds to traverse it. Additionally, the data suggest that for the compounds examined, the neutral acidic:neutral phospholipid ratios of the cell envelope, also influence the permeation of it. PMID- 2890734 TI - Influence of time and chloride ions on the interaction of cisplatin with human albumin in-vitro. AB - The interaction of cis-dichlorodiammineplatinum (II) (cisplatin) with human serum albumin (HSA), dissolved in phosphate buffer with or without sodium chloride (0.1 M) has been examined at pH 7.4 and mu = 0.154. Equal volumes of cisplatin and HSA solutions were incubated at 37 degrees C for various times and filterable platinum concentrations versus time measured by flameless atomic absorption spectrophotometry. Binding kinetics differed depending on the buffer solutions used and on the time elapsing between cisplatin dissolution and outset of incubation with HSA. Experimental data were fitted to a theoretical equation used to calculate the number of nucleophilic sites per HSA molecule. Titrations of the HSA sulphydryl group content before and after incubation with a cisplatin solution were made, from which it was shown that the lone SH-group of the HSA macromolecule is involved in cisplatin binding. We also studied HSA's sensitivity towards denaturing agents when it was complexed with cisplatin. This sensitivity was decreased upon cisplatin binding. Also, the binding capacities of HSA and the HSA-Pt(II) complex to both tryptophan and warfarin were compared to determine the possible influence of cisplatin upon the binding to HSA of other drugs; this influence was negligible. PMID- 2890735 TI - Macrophage activation through phagocytosis of muramyl dipeptide encapsulated in gelatin microspheres. AB - Gelatin microspheres containing muramyl dipeptide (MDP) were prepared by crosslinking with glutaraldehyde. They were added to mouse peritoneal macrophages (PMs) to potentiate the tumour growth inhibitory activity. The PMs which had internalized the microspheres exhibited growth inhibitory activity to syngeneic, allogeneic, and xenogeneic tumour cells. A similar effect was observed for PMs incubated with free MDP, but the MDP encapsulated in the microspheres was more efficient in enhancing the PM activity than the free MDP. In addition, PMs were activated in much shorter periods upon incubation with the microsphere encapsulated MDP. The duration of activity could be controlled for up to 7 days by changing the extent of crosslinking of microspheres. Dose-response experiments established that microsphere-encapsulated MDP is able to activate PMs to inhibit growth of tumour cells at concentrations approximately 2000 times lower than the free MDP present in media. The activity of PMs was also acquired on intraperitoneal injection of the microspheres, in contrast to PMs with the free MDP. PMID- 2890736 TI - Cardiovascular responses in rats with chronic renal failure. AB - Cardiovascular responses were determined in rats with chronic renal failure (CRF) produced by five sixths nephrectomy and in sham-operated rats. The conscious systolic blood pressure of rats with CRF was significantly higher than the pressure in controls although, after anaesthesia, there were no significant differences in the mean arterial pressure between the two groups of rats. The pressor responses to noradrenaline in rats with CRF were not significantly different from those recorded in sham-operated controls. The bradycardia elicited by electrical stimulation of the vagus nerve was significantly diminished in rats with CRF. However, indomethacin treatment (1 mg kg-1 s.c. twice daily for 2 days) abolished the differences in response to vagal stimulation. Changes in heart rate in response to electrical stimulation of the cervical sympathetic nerve and to bolus i.v. injections of isoprenaline and carbachol were similar in rats with CRF and controls. The most notable disturbance of cardiovascular function in rats with CRF is the diminished cardiac chronotropic response to vagal stimulation which appears to be mediated by a presynaptic action of prostaglandins. PMID- 2890737 TI - Hypothermic effect of GABA in conscious stressed rats: its modification by cholinergic agonists and antagonists. AB - gamma-Aminobutyric acid (GABA) intraperitoneally injected (i.p.) produced a dose dependent hypothermia in restrained rats. GABA-induced hypothermia (1000 mg kg-1) was antagonized by pretreatment with atropine (2.5 and 10 mg kg-1 i.p.), hyoscine butylbromide (2.5 mg kg-1 i.p.), hexamethonium (0.75 mg kg-1 i.p.) or physostigmine (0.2 mg kg-1 s.c.). Hexamethonium (7.5 mg kg-1 i.p.) did not influence the hypothermia induced by GABA. The antagonism by physostigmine of GABA-induced hypothermia was attenuated by pretreatment of the rats with either alpha-methyl-p-tyrosine (200 mg kg-1 i.p.) or hexamethonium (7.5 mg kg-1 i.p.), but it was potentiated by either atropine (5 mg kg-1 i.p.) or hexamethonium (0.75 mg kg-1 i.p.). The data indicate that GABA-induced hypothermia may be partly mediated by acetylcholine release. Muscarinic receptors may play an important role in the effect of GABA. The results support the hypothesis of nicotinic presynaptic receptors modulating noradrenergic nerve endings that play a part in the hypothermic response of GABA. PMID- 2890739 TI - The effect of blending time on particle adhesion in a model interactive system. AB - The adhesive tendency of drug particles in a model drug carrier interactive system increased with blending time. The degree of interaction was measured using a centrifuge technique; the resultant adhesion profile of per cent retained on the carrier versus the square of the speed of rotation was a logarithmic normal function that allowed the determination of the S50 to characterize the adhesion tendency. The relative degree of adhesion of the drug particles in the interactive mixtures and the rate to attain adhesion saturation in the interactive system during the mixing process was markedly different for the three mixtures studied. The increased adhesive tendencies during blending were probably associated with triboelectrification of the drug and carrier particles. PMID- 2890738 TI - An HPLC assay procedure of sensitivity and stability for measurement of acetylcholine and choline in neuronal tissue. AB - A method is presented for the sensitive and specific determination of acetylcholine and choline in neuronal tissue. The method is based on the separation of acetylcholine and choline by reversed-phase HPLC, passing the eluent into a post-column reactor containing choline oxidase and acetylcholinesterase covalently bound to vinyl sulphone bonded onto a hydroxyethyl methacrylate support, and electrochemical detection of the hydrogen peroxide formed. The limit of detection of the procedure is 1 pmol for acetylcholine and 500 fmol for choline. The excellent baseline stability of the method ensures the rapid and reliable processing of a large number of samples. PMID- 2890740 TI - The packing characteristics of physical and formulated mixtures of oxytetracycline and lactose powders. AB - Measurements have been made of the tap densities and angles of internal flow of physically mixed and formulated mixtures of oxytetracycline and lactose powders. The differences between the two types of mixtures are ascribed to differences in the packing and surface morphologies of the particles. PMID- 2890741 TI - Evaluation of reversible polymorphic phase transitions by thermal analysis. AB - Crystalline states of 1,2-dihydro-6-neopentyl-2-oxonicotinic acid, an investigational antidiabetic drug, were evaluated by thermal analyses. Two polymorphs were detected for the drug, Form I (m.p. 193 degrees C) and Form II (m.p. 196 degrees C). Interconversion of the polymorphs upon cyclic solid-melt transitions provided confirmation of the crystal forms. Solidification of the melt was observed to occur either at 162 or 182 degrees C with the formation of Form I or Form II crystals, respectively. Form I underwent partial conversion to Form II upon heating at 10 degrees C min-1 when nucleating crystals of Form II were present in the sample. Differential scanning calorimetry (DSC) thermograms were recorded for different lots of the drug, solvent-recrystallized samples, and a series of known mixtures of Form I and II polymorphs. The study illustrates the usefulness of cyclic heat-cool studies to characterize polymorphic crystal forms of drugs. PMID- 2890742 TI - Determination of the aryltetralin lignan content of podophyllum resins and roots/rhizomes. AB - A simple, quantitatively reproducible method for determining the aryltetralin lignan content of the resins and roots/rhizomes of Podophyllum hexandrum and P. peltatum is described. The method confirms that P. hexandrum resins and roots/rhizomes contain approximately four times the quantity of lignans as do those of P. peltatum and also that there is a significant variation in the lignan content of P. hexandrum resins. PMID- 2890743 TI - Binding of chlorpromazine, phenytoin and aspirin to the erythrocytes and lipoproteins in whole human blood. AB - The quantitative binding of 14C-labelled chlorpromazine, phenytoin or aspirin (at 10 microM) to blood cells and plasma lipoproteins in whole human blood or to the washed erythrocytes in an isotonic protein-free medium has been studied. The fractions of chlorpromazine, phenytoin and aspirin bound to the blood cells in whole blood amounted to about 40, 14 and 2% of the total amount added, and those to the lipoproteins amounted to 7, 2 and 1%, respectively. Their binding to the washed erythrocytes in protein-free medium was 95, 76 and 40%, respectively. Their octanol:water partition coefficients were 214, 170 and less than 0.1, respectively. These results suggest that the amphiphilic drugs with relatively high hydrophobicity may be bound to the blood cells, mainly to erythrocytes, to considerable extents when administered clinically, and also that their binding to plasma lipoproteins may not be negligible. PMID- 2890744 TI - Prostaglandin D2-induced catalepsy in rats: role of 5-hydroxytryptamine. AB - Prostaglandin D2 (PGD2), the major PG in the rat brain, induced a dose-related catalepsy in rats on intracerebroventricular (i.c.v.) administration. This cataleptic response was significantly attenuated following the i.c.v. administration of pharmacological agents that decrease rat brain 5 hydroxytryptamine (5-HT) activity. PGE1 synergized but PGF2 alpha antagonized the catalepsy induced by PGD2. PGD2 and PGE1 have previously been shown to augment rat brain 5-HT activity, whereas PGF alpha inhibited it. It is therefore likely that the observed effects of these PGs on catalepsy involve a central 5-HT mechanism. PMID- 2890745 TI - Desensitization of beta-adrenoceptors following repeated injections of 2 substituted 4-phenylquinolines. AB - The chronic effects of five 2-substituted 4-phenylquinoline derivatives on the sensitivity of the noradrenergic cyclic AMP-generating system in the rat brain cortex have been determined, and compared with those of the typical and atypical antidepressants imipramine and trazodone, respectively. Acute treatment (single i.p. dose of 20 mg kg-1) and sub-chronic treatment (20 mg kg-1 daily for 10 days) induced no significant desensitization of the beta-adrenoceptors. However, chronic treatment (20 mg kg-1 daily for 3 weeks) significantly decreased the isoprenaline-induced increase in cyclic AMP, suggesting desensitization. This effect, coupled with previous findings, points to a potential role of these compounds as antidepressants. PMID- 2890746 TI - Lack of inotropic selectivity of phosphodiesterase enzyme inhibitors in-vitro. AB - Phosphodiesterase enzyme (PDE) inhibitors form a diverse category of chemical structures which display positive inotropic activity, but it is unclear as to how force/rate selective these are on the heart. In this study several recently developed PDE inhibitors, almost all of which are selective for the cardiac PDE III isoenzyme, were compared with the xanthine PDE inhibitor IBMX and with ouabain and the direct and indirect adenylate cyclase activators, forskolin and isoprenaline, respectively. These compounds were active in increasing paced guinea-pig left atrial force, the order of potency being: isoprenaline greater than ouabain greater than forskolin greater than pimobendan greater than IBMX greater than sulmazole greater than buquineran greater than carbazeran greater than milrinone greater than piroximone greater than amrinone. Ro 13-6438 and enoximone were however, both inactive. With the exception of buquineran and carbazeran, which produced bradycardia and were therefore force specific, all of the recently discovered PDE inhibitors increased the rate of contraction of the right atria and they were rate selective to the same extent as IBMX, isoprenaline and forskolin. Sulmazole, the only force selective PDE inhibitor of the compounds studied, was intermediate between IBMX and ouabain in force/rate selectivity and pimobendan showed no selectivity. Since both these agents also possess other actions, then these results suggest that in general, PDE III inhibitors do not show advantageous force selectivity in guinea-pig atria. PMID- 2890747 TI - Beta-adrenergic activities of octopamine and synephrine stereoisomers on guinea pig atria and trachea. AB - The activities of the (-)- and (+)-forms of m- and p-octopamine and m- and p synephrine on beta 1- and beta 2-adrenoceptors in guinea-pig atria and trachea have been compared with that of noradrenaline. The rank order of potency of the ( )-forms on beta 1-adrenoceptors was noradrenaline greater than m-synephrine greater than m-octopamine = p-octopamine greater than p-synephrine. m-Synephrine was 100-fold, m- and p-octopamine about 6000-fold, and p-synephrine about 40,000 fold less active than noradrenaline. The (+)-forms were 1-2 orders of magnitude less active than their (-)-counterparts. The four (-)-compounds were more than four orders of magnitude less active than noradrenaline on beta 2-adrenoceptors, and the (+)-forms had no detectable activity in concentrations as high as 10(-4) M. If m- and p-octopamine are co-released with noradrenaline in amounts proportional to their concentration, their activities at these structures are too low to be physiologically significant. PMID- 2890748 TI - Postsynaptic alpha 1-adrenoceptor mechanisms in rat vas deferens and ageing. AB - Postsynaptic alpha 1-adrenoceptor mechanisms in vasa deferentia isolated from 3, 6, 18 and 40 week-old rats were studied by analysis of the concentration-response curve of noradrenaline and the Scatchard plot of specific binding of [3H]prazosin to microsomal fractions. The maximum tension developed by noradrenaline also increased with age from 3 to 18 weeks. The efficacy of noradrenaline and capacity of the maximum binding sites of [3H]prazosin increased with increasing age, while the dissociation constants of noradrenaline (KA) and prazosin (Kd) were not changed with age. The increase of the maximum tension was proportional to the increase in efficacy. The increase of efficacy for noradrenaline in the vasa deferentia from rats of different ages is due to the increase in the total concentration of postsynaptic alpha 1-adrenoceptors. PMID- 2890749 TI - Effects of chronic treatment with amiodarone on hepatic demethylation and cytochrome P450. AB - The effect of chronic treatment with amiodarone on hepatic oxidative metabolism using an in-vivo [14C]aminopyrine breath test and on hepatic cytochrome P450 was examined in Wistar rats. Aminopyrine demethylation was significantly impaired but returned to pretreatment values following amiodarone for 4 weeks. In contrast the levels of cytochrome P450 were significantly depressed during treatment and at 4 weeks following treatment. While an inhibitory effect on oxidative metabolism may explain the reported drug interactions with amiodarone, the discrepancy between its in-vivo effects and cytochrome P450 levels may suggest the development of 'compensatory' extra-hepatic site of drug metabolism. PMID- 2890750 TI - Comparative biodistribution of methotrexate and monoclonal antibody-methotrexate complexes in mice. AB - The biodistribution of radiolabelled methotrexate and immune complexes of methotrexate and a murine monoclonal anti-methotrexate antibody has been compared in mice. Complexes formed in-vitro with the antibody, but not with control immunoglobulin. The complexes were, characteristically, acid labile. In-vivo, blood levels, organ distribution and whole body catabolism of methotrexate in immune complexes were similar to those of free antibody, and markedly different from those of free drug. These findings suggest the feasibility of prolonging the survival of drugs and altering in-vivo distribution using complexes with monoclonal antibodies. PMID- 2890751 TI - The influence of aromatic substituents on the binding of substituted benzamides to dopamine D-2 receptors: congruent QSAR and MEP analyses. PMID- 2890752 TI - Reflex sympathetic dystrophy syndrome. Review with podiatric case studies. PMID- 2890753 TI - Pedal envenomation by a stingray. A case report. PMID- 2890754 TI - Recovery of chronotropic responsiveness after systemic 6-hydroxydopamine treatment: studies in the pithed rat. AB - In pithed rats, neurally mediated chronotropic responses to thoracolumbar stimulation were reduced substantially 1 day after animals were treated with the neurotoxin 6-hydroxydopamine (6-HDA), which produced a subtotal destruction of postganglionic sympathetic nerve terminals. However, the chronotropic responses of 6-HDA-treated rats recovered to near normal within 1 week despite 90% depletion of cardiac norepinephrine (NE). This recovery of function appeared to depend upon function in surviving sympathetic nerves, and was associated with increased synthesis and release of NE from those neurons as well as diminished inactivation of NE. The gradual development of post-junctional changes, most notably an increase in the density of myocardial beta adrenergic receptors, resulted in enhanced sensitivity to NE and contributed to cardiac function 3 weeks after 6-HDA treatment. In addition, the adrenal medulla increased its synthesis of catecholamines after 6-HDA treatment and thereby contributed to cardiac function, which was especially evident during prolonged sympathoadrenal stimulation. Some of these same adaptations have been observed when rats are subjected to chronic stress, and thus common mechanisms of neuroplasticity may mediate the sympathoadrenal responses to stress and to subtotal injury. PMID- 2890755 TI - Different affinity states of alpha-1 adrenergic receptors defined by agonists and antagonists in bovine aorta plasma membranes. AB - Evidence for a nonlinear relationship between alpha-1 adrenergic receptor occupancy and tissue responses, together with the finding of different affinity states for agonist binding, has raised the possibility of functional heterogeneity of alpha-1 adrenergic receptors. We have conducted studies to examine: 1) binding characteristics of [3H]prazosin, 2) competition of antagonists at these sites and 3) different affinity states of the receptor for agonists and modulation of these states by 5'-guanylylimidodiphosphate [Gpp(NH)p]. A plasma membrane-enriched vesicular fraction (F2; 15%/33% sucrose interphase) was prepared from the muscular medial layer of bovine thoracic aorta. [3H]Prazosin binding was characterized by a monophasic saturation isotherm (KD = 0.116 nM, Bmax = 112 fmol/mg of protein). Antagonist displacement studies yielded a relative potency order of prazosin greater than or equal to WB4104 much greater than phentolamine greater than corynanthine greater than yohimbine greater than or equal to idazoxan greater than rauwolscine. Competition curves for unlabeled prazosin, WB4101 (2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4 benzodioxane) and phentolamine were shallow and were best modeled to two binding sites with picomolar and nanomolar KD values. Gpp(NH)p was without effect on antagonist affinity. Agonist (epinephrine, norepinephrine and phenylephrine) competition with [3H]prazosin binding was biphasic with pseudo-Hill slopes less than 1.0. Binding was best described by a two-site model in which the average contribution of high affinity sites was 23% of total binding. KD values for the high affinity site ranged from 2.9 to 18 nM, and 3.9 to 5.0 microM for the low affinity site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890756 TI - Somatostatin effects on gastric electrolytes and pepsin in dogs with various secretory stimuli. AB - To determine possible sites and mechanisms of action of somatostatin (SS) in gastric secretory mucosa, secretion of pepsin, H+, Cl-, Na+ and K+ was stimulated in conscious fistula dogs by i.v. infusion of bethanechol, pentagastrin and histamine in the absence and presence of SS-14. At low dose (0.5 micrograms or 300 pmol/kg/h), SS-14 potently inhibited H+ and pepsin stimulated by bethanechol (80 micrograms/kg/h) to less than 5% of control; it required 2 micrograms or 1200 pmol/kg/h of SS-14 to achieve similar inhibition of pentagastrin (1.5 micrograms/kg/h)-stimulated secretion. In both cases, gastric [K+] was depressed by SS-14 infusion and recovered before H+ and pepsin. Similar sensitivity to SS suggests a Ca++-dependent mechanism or pathway of stimulation by gastrin similar to that by cholinergic agonists. By contrast, histamine, which acts via cyclic AMP pathways, was not inhibited by a large dose of SS-14 (20 micrograms/kg/h). SS inhibition is thus agonist (or pathway)- rather than organ- or cell-specific. PMID- 2890757 TI - Muscarine-stimulated neurotransmitter release from PC12 cells. AB - The effect of muscarine on neurosecretion was studied in the rat pheochromocytoma cell line, PC12. When PC12 cells were exposed to muscarine the cells responded rapidly with elevation of cellular inositol trisphosphate levels, elevation of intracellular free Ca++ and release of stored transmitter. These three phenomena were totally inhibited by the muscarinic antagonist, atropine, but were unaffected by the nicotinic antagonist, d-tubocurarine. Muscarine did not stimulate the production of cyclic GMP in these cells. The muscarine-stimulated increases in inositol trisphosphate, intracellular free Ca++ and neurotransmitter release displayed similar time courses and concentration dependencies suggesting that the secretion observed may be associated with the formation of inositol trisphosphate and elevation of intracellular free Ca++. The increase in intracellular free Ca++ appeared to be due to a mobilization of Ca++ from intracellular stores inasmuch as the increase in intracellular free Ca++ was not inhibited by the voltage-dependent Ca++ channel antagonist, nifedipine, at concentrations demonstrated to block K+-induced Ca++ influx into the cells, and little or no uptake of 45Ca++ was noted when cells were stimulated with muscarine. Elevation of inositol trisphosphate, intercellular free Ca++ and stimulation of transmitter release were, however, inhibited by the absence of extracellular Ca++. The results suggest that muscarine-stimulated release of neurotransmitter may be associated with an inositol trisphosphate-induced mobilization of intracellular Ca++. PMID- 2890758 TI - Alpha-1 adrenoceptor-induced Ca++ movements in rat aorta: antagonism by phenoxybenzamine and N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline. AB - The influx of 45Ca++ produced by l-norepinephrine (3 X 10(-7) or 10(-5) M) and K+ (100 mM) in rat aorta was not significantly influenced by phenoxybenzamine (1 or 3 X 10(-8) M) present for 5 or 10 min. However, the l-norepinephrine (3 X 10(-7) or 10(-5) M)-mediated 45Ca++ efflux was markedly attenuated by this treatment. Higher concentrations of phenoxybenzamine, as well as extension of the time of exposure, impaired the 45Ca++ influx to l-norepinephrine, but not that to K+. In contrast, prazosin (10(-9)-10(-7) M), as well as N-ethoxycarbonyl-2-ethoxy-1,2 dihydroquinoline (10(-7) or 10(-6) M for 5 or 10 min), was equally effective in antagonizing the 45Ca++ in and efflux caused by l-norepinephrine. Exposure of rat aorta to 1.3 X 10(-9) M phenoxybenzamine for 30 min significantly shifted the log concentration-contractile response curve to the full alpha-1 adrenoceptor agonist, l-phenylephrine, to the right and reduced its maximum response but failed to alter the contraction to the partial agonist Sgd 101/75 (indanidine). Conversely, incubations with 2.0, 2.2 and 3.0 X 10(-8) M N-ethoxycarbonyl-2 ethoxy-1,2-dihydroquinoline invariably affected the contractions to Sgd 101/75 more than those to l-phenylephrine. In pithed rats, N-ethoxycarbonyl-2-ethoxy-1,2 dihydroquinoline (1 or 2 mg/kg i.v., -30 min), as well as phenoxybenzamine (0.1 mg/kg i.v., -30 min), enhanced the effectiveness of nifedipine to inhibit the vasopressor responses to the alpha-1 adrenoceptor stimulant, cirazoline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890759 TI - Amino acid influences on seizures elicited within the inferior colliculus. AB - Using a model in which seizure activity was elicited electrically from the inferior colliculus, the influence of both inhibitory and excitatory putative neurotransmitter amino acids on this seizure activity was assessed by manipulating neurotransmitter amino acid function. It was found that i.c.v. administration of the inhibitory amino acids taurine (2.5 micrograms) or glycine (30 micrograms), or the gamma-aminobutyric acidA agonist, muscimol (300 ng), significantly elevated the threshold current necessary to initiate seizure activity from the inferior collicular cortex. Similarly, the microinjection of muscimol (10 or 30 ng) or racemic baclofen (20 or 60 ng), a gamma-aminobutyric acidB agonist, into the inferior collicular cortex significantly elevated the seizure threshold current, but inferior collicular microinjections of taurine (1 microgram) or glycine (1 microgram) exerted no effect on the seizure threshold current. When excitatory amino acid influences were assessed on seizure production, neither ventricular administration of glutamate or aspartate (100 micrograms) nor inferior collicular administration of glutamate (1 or 10 micrograms) or aspartate (10 micrograms) changed the seizure initiation threshold. Although the site administration of 30 or 100 ng of N-methyl-D aspartic acid did not alter the seizure initiation threshold, 300 ng of N-methyl D-aspartic acid significantly lowered the amount of electrical stimulation necessary to elicit the seizure activity. Conversely, blockade of N-methyl-D aspartic acid receptors in the inferior colliculus with L-3-amino-7 phosphonoheptanoic acid (100 ng) or gamma-glutamylglycine (200 ng) significantly elevated the threshold current for seizure production, whereas microinjection of DL-3-amino-phosphonobutyric acid (200 ng) or glutamic acid diethyl ester (1 microgram) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2890760 TI - Role of calcitonin gene-related peptide as cardiotonic neurotransmitter in guinea pig left atria. AB - A potential neurotransmitter role of calcitonin gene-related peptide (CGRP) in nonadrenergic noncholinergic (NANC) nerves was examined in the left atrium of guinea pigs. In the presence of atenolol (beta-adrenoceptor antagonist), prazosin (alpha adrenoceptor antagonist) and atropine (muscarinic antagonist), transmural nerve stimulation (TNS) elicited a positive inotropic response which was slow in both onset and decay. Inasmuch as this TNS-induced positive inotropic response was abolished by tetrodotoxin, it can be considered that the response was mediated by intracardiac NANC nerves. Numerous CGRP-like immunoreactive nerves were detected in the left atrium. Exogenously applied CGRP produced a positive inotropic response in a dose-dependent manner. Neither substance P nor vasoactive intestinal polypeptide exerted a positive inotropic effect. CGRP-like immunoreactive nerves and the TNS-induced NANC response was not affected by surgical sympathectomy of the heart or reserpine pretreatment but were specifically abolished by the pretreatment of animals with capsaicin. These results suggest that CGRP is the potential neurotransmitter of NANC nerves in the left atrium of guinea pigs. PMID- 2890761 TI - N-methyl-D-aspartate receptors mediate hypoxic neuronal injury in cortical culture. AB - The ability of several glutamate receptor antagonists to reduce hypoxic cortical neuronal injury was quantitatively examined in cell cultures derived from fetal mice. Cultures exposed to hypoxia for 8 hr showed by the following day widespread neuronal injury, which was substantially attenuated by addition of the specific N methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (APV). The protective effect of APV was concentration dependent (ED50 about 2 microM) and stereospecific (D-APV approximately 100 times more potent that L-APV). Neuron protective effects were also observed with several other NMDA antagonists: 2 amino-7-phosphonoheptanoate, phencyclidine and (+)-SKF 10,047 [(+)-N allylnormetazocine]--as well as with the nonspecific glutamate antagonists D glutamylglycine and kynurenate. In addition, a similar antagonist profile was observed with a chemical model of hypoxic neuronal injury, produced by brief exposure to high concentrations of cyanide. In contrast, 1 mM concentrations of glutamate diethylester and gamma-aminomethyl sulfonate, compounds reported in some studies to preferentially antagonize non-NMDA glutamate receptors, failed to protect neurons against either hypoxia or cyanide. These results are consistent with the hypothesis that NMDA receptors are preferentially involved in the pathogenesis of hypoxic cortical neuronal injury and suggest that cortical cell culture may be a useful system in which to quantitatively characterize the pharmacology of that injury. PMID- 2890762 TI - Tensile bond strength of low-fusing solder joints with the use of a nickel chromium-beryllium base metal alloy. PMID- 2890763 TI - Neuroleptic dose: a statistical model for analyzing historical trends. AB - Neuroleptic dosing practices during inpatient treatment of schizophrenia were examined for 1490 admission episodes during 1973 through to 1982 in two wards of a university hospital. Chlorpromazine-equivalent dose levels (CPZE) declined 50% between 1974 and 1980. As expected, length of treatment and choice of drug were both strongly related to CPZE. The general drop in CPZE is not explained by shorter treatment and changing choice of drug, however. Oral fluphenazine, haloperidol, and depot fluphenazine are used to higher maximum levels than chlorpromazine and other neuroleptics, when maximum dose is reached after one week or longer. The results illustrate that by seeking an appropriate statistical model, aggregate trends in dosing practices can be described while avoiding several of the shortcomings of earlier surveys of hospital practice. PMID- 2890764 TI - A taxometric method for diagnosis of tardive dyskinesia. AB - A taxometric method for diagnosis of drug-induced tardive dyskinesia is described. The method, using items from the Abnormal Involuntary Movement Scale (AIMS) as indicators of the syndrome, is applied in a sample of children diagnosed earlier as autistic and participating in an ongoing treatment program. The method includes procedures for estimation of the prevalence rate of the syndrome and the valid positive and false positive rates for each indicator of the syndrome and it includes tests (referred to as "consistency tests") for checking the internal validity or goodness-of-fit of the statistical model. The agreement of the taxometric classification with that obtained by using criteria suggested by Schooler and Kane was very good. In general, the results were encouraging enough to warrant further study of this kind of method for the detection and diagnosis of tardive dyskinesia. PMID- 2890765 TI - Tardive dyskinesia. PMID- 2890766 TI - Inappropriate traditional treatment resulting in limb amputation. AB - Four cases are described where inappropriate treatment by the traditional Nepali spiritualist healer or jhankri resulted in amputation of a previously healthy limb. Such treatments may involve the use of tourniquets, burning, scarification and herbal remedies. PMID- 2890767 TI - ATP synthase from bovine mitochondria. The characterization and sequence analysis of two membrane-associated sub-units and of the corresponding cDNAs. AB - ATP synthase from bovine mitochondria is a complex of 13 different polypeptides, whereas the Escherichia coli enzyme is simpler and contains eight subunits only. Two of the bovine subunits, b and d, which had not been characterized, have been isolated from the purified enzyme. Subunits with sizes corresponding to bovine subunits b and d are evident in preparations of the enzyme from mitochondria of other species. Partial protein sequences have been determined by direct methods. On the basis of some of this information, two oligonucleotide mixtures, 17 and 18 bases in length, have been synthesized and used as hybridization probes in the isolation of clones of the cognate cDNAs. The sequences of the two proteins have been deduced from their DNA sequences. Subunit b is 214 amino acid residues in length and has a free N terminus. Subunit d is 160 amino acid residues long. Its N-terminal alanine is blocked by an N-acetyl group, as demonstrated by fast atom bombardment mass spectrometry of N-terminal peptides. The sequence near the N terminus of the b subunit is made predominantly of hydrophobic residues, whereas the remainder of the protein is mainly hydrophilic. This N-terminal hydrophobic region may be folded into an alpha-helical structure spanning the lipid bilayer. In its distribution of hydrophobic residues, this protein resembles the b subunits of ATP synthase complexes in bacteria and chloroplasts. The b subunit in E. coli forms an important structural link between the extramembrane sector of the enzyme F1, and the intrinsic membrane domain, FO. It is proposed that the bovine mitochondrial subunit b serves a similar function. If this is so, the mitochondrial enzyme, as the chloroplast ATP synthase, contains equivalent subunits to all eight of those that constitute the E. coli enzyme. Subunit d has no extensive hydrophobic sequences, and is not apparently related to any subunit described in the simpler ATP synthases in bacteria and chloroplasts. PMID- 2890768 TI - Chelating-agent suppression of cadmium-induced hepatotoxicity. AB - The administration of sodium N-methyl-N-dithiocarboxy-D-glucamine (NaG) at 500 mg/kg, i.p., or sodium calcium diethylenetriaminepentaacetic acid (DTPA) at 632.5 mg/kg, i.p., reduces the serum enzyme levels characteristic of hepatic damage following the intravenous administration of cadmium chloride (3.5 mg CdCl2.2.5H2O/kg). Some effect on serum enzyme levels was found even when the interval between administration of cadmium chloride and that of the antagonist was as great as 4 h. The enzymes examined included aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (SGPT), and alkaline phosphatase (AP). A histopathological examination of the livers of such animals also reveals the presence of a significant protective action. PMID- 2890769 TI - Interleukin-3 modulation of mouse bone marrow derived mast cell receptors for somatostatin. AB - Receptors for somatostatin (SOM) were identified on mouse bone marrow derived mast cells (MBMMC) and shown to vary in expression with the state of proliferation and differentiation of the MBMMC. Flow cytometric studies of the binding of fluorescein-labeled SOM and concurrent analyses of the binding of [125I]SOM demonstrated that the population of MBMMC capable of recognizing SOM specifically is that exhibiting a proliferative response to interleukin-3. The MBMMC that bound SOM reached a maximal number at 72 hr following the addition of interleukin-3, and were distributed principally in the G2/M phase of the cell cycle. SOM did not influence directly the proliferative responses of MBMMC to interleukin-3. The level of expression of SOM receptors thus may reflect the state of differentiation of mast cells, as well as determining the functional sensitivity to the inhibitory effects of SOM. PMID- 2890770 TI - HLA-DR restriction-fragment-length polymorphisms in narcolepsy. AB - Seventeen white patients from the Stanford Sleep Disorders Clinic complaining of excessive daytime somnolence (EDS) were selected for restriction-fragment-length polymorphism (RFLP) studies. Fourteen of the patients with clinically diagnosed narcolepsy were seropositive for DR2. RFLP analysis of these patients compared with a homozygous DR2-Dw2 cell line failed to reveal any polymorphism when digested with six restriction endonucleases and hybridized with three different cDNA probes. None of the three patients with central nervous system hypersomnia, a syndrome similar to narcolepsy, were DR2-positive. We conclude that any polymorphism of the DR beta, DQ alpha, or DQ beta genes of DR2 narcoleptics that might distinguish them from DR2 normals cannot be resolved through RFLP analysis. PMID- 2890771 TI - Noradrenergic sympathetic innervation of the spleen: II. Tyrosine hydroxylase (TH)-positive nerve terminals form synapticlike contacts on lymphocytes in the splenic white pulp. AB - Immunocytochemistry was used to demonstrate tyrosine hydroxylase (TH)-positive profiles in the spleen of the adult Fischer 344 rat. At the light microscopic level, numerous varicose nerve profiles were seen in the white pulp, particularly surrounding the central arteries and their arteriole branches. At the electron microscopic level, varicosities were seen in close proximity to smooth muscle cells of the arteries, and directly abutting lymphocytes (presumable T lymphocytes) of the nearby periarteriolar lymphatic sheath. There were no intervening cell processes between the TH-positive terminals and the lymphocyte. The opposing membranes were smooth and evenly spaced approximately 6 nm apart. Additional TH-positive nerve profiles were seen in the inner marginal zone and within trabeculae. The correlation between this immunocytochemical staining and previously demonstrated histofluorescence for norepinephrine leads to the conclusion that lymphocytes in the splenic white pulp have direct associations with noradrenergic fibers of the sympathetic nervous system. This association provides a route by which the autonomic nervous system could directly influence specific immune system effector cells. PMID- 2890772 TI - The use of a radiorespirometric assay for testing the antibiotic sensitivity of catheter-associated bacteria. AB - A 14C-radiorespirometric assay was used to show the sensitivity of fixed-film (sessile), catheter-associated and free-living (planktonic) cells of Pseudomonas aeruginosa to varying concentrations (100 micrograms/mL to 1000 micrograms/mL) tobramycin sulfate. This strain of P. aeruginosa has an MIC of 0.6 microgram/ml and an MBC of 50 micrograms/mL when tested by conventional methods. When 14C glutamic acid was used as a substrate in this radiorespirometric assay, it could be completed in less than one hour and planktonic samples showed a significant reduction in mineralization activity (evolution of 14CO2) within eight hours of the antibiotic challenge. These changes in respiratory activity appeared to be dose and time dependent. Within 18 hr. at 1000 micrograms/mL, there was no significant residual respiratory activity in planktonic samples. Some residual respiratory activity was detected, however, in samples exposed to 100 micrograms/mL for 36 hours. The mineralization activity of sessile catheter associated bacteria was unaffected by four hr. and eight hr. exposures to 1000 micrograms/mL of the antibiotic. A significant reduction in respiratory activity was recorded in catheter samples exposed for 18 hr. or more at each concentration examined. Unlike the planktonic samples, however, the antibiotic challenge failed to eradicate the metabolic activity of the attached bacteria. Antibiotic stressed, catheter-associated bacteria transferred to a post-exposure enrichment broth showed a limited ability to re-establish respiratory activity. This apparent recovery was limited to antibiotic exposures less than 24 hr. and was not observed in planktonic samples. The radioisotopic assay is a non-culture method which can be used to assess the antibiotic sensitivity of both planktonic bacteria and "in situ" biofilm populations. Clinically, it can be used to demonstrate that some adherent biofilm bacteria can survive the exposure to antibiotics that is achieved in routine chemotherapy. PMID- 2890773 TI - [Bronchial asthma and airway hypersensitivity--2) Theory of beta-adrenergic receptor blockade]. PMID- 2890774 TI - [Progress of therapeutic agents for asthma--1) Progress of anti-asthmatic agents]. PMID- 2890775 TI - [Percutaneous transluminal angioplasty of aortic stenosis in a patient with Takayasu aortitis]. PMID- 2890776 TI - Expression of proliferation-associated nuclear antigen in human malignancies. AB - 40 specimens consisting of 27 carcinomas, 9 lymphomas, 2 thymomas, 1 sarcoma and 1 neurinoma were studied by immunoperoxidase technique to demonstrate a cell proliferation-associated antigen defined by proliferating cells (PC) antibody. Though PC antibody expression did not seem to correlate well with histologic grading of carcinomas, positivity to this was consistently more intense in carcinomas than in normal epithelia. Correlation with histologic grading of lymphomas was more significant: the high grade types, e.g. ATL, exhibited greater positivity than intermediate grade types, e.g. diffuse medium lymphoma and certainly much more than low grade types, e.g. follicular lymphomas. These data were compared to another proliferation-associated antigen, the transferrin receptor. PMID- 2890777 TI - Effect of prostacyclin in preventing cinchophen-induced gastric ulcers in the dog. PMID- 2890778 TI - Non-neural electrical responses of smooth muscle cells of the rabbit basilar artery to electrical field stimulation. AB - In smooth muscle cells of the rabbit basilar artery, field stimulation evoked a depolarizing response which consisted of a fast (1-3 s duration) and a following slow (1-4 min duration) component. The amplitude of these responses increased in an intensity-dependent manner and, when exceeding 10-15 mV, a spike potential was generated. During generation of the slow depolarization, ionic conductances of the membrane were increased. When outward current pulses with long duration (2-3 s) were applied to the smooth muscle using the partition stimulating method, electrotonic potentials and spike potentials were generated. The cessation of the current pulse caused repolarization of the membrane with time constant of 250-350 ms. The depolarizing responses were resistant to tetrodotoxin, sympathetic transmission blocking agents (guanethidine, bretylium, or 6-hydroxydopamine treatment), receptor antagonists for 5-hydroxytryptamine (methysergide), dopamine (haloperidol), ACh (atropine), noradrenaline (phentolamine), ATP (alpha,beta mATP) or histamine (mepyramine), blockade of synthesis of prostaglandins or thromboxane A2 (indomethacin) or high Mg2+, low Ca2+ solution. Smooth muscle cell membrane of the basilar artery was depolarized by 5-hydroxytryptamine (above 0.1 microM) or histamine (above 10 microM) but not by ACh (up to 100 microM) or noradrenaline (up to 10 microM). The depolarization induced by 5 hydroxytryptamine or histamine was antagonized by methysergide or mepyramine, respectively. Denervation of the vessel by storing in a cold condition (4 degrees C) decreased but did not abolish the depolarizing response. The decrease in amplitude of the depolarizing response during cold storage was attributed to associated depolarization of the smooth muscle membrane. Internal perfusion of the vessel with distilled water abolished generation of the depolarizing response, and this procedure also abolished the endothelium-dependent relaxation induced by ACh during the potassium contraction. The results suggest that the depolarizing response evoked by field stimulation is generated by substances released from non-neural components, possibly from the endothelial cells. PMID- 2890779 TI - An antagonistic activity of etizolam on platelet-activating factor (PAF). In vitro effects on platelet aggregation and PAF receptor binding. AB - The antagonistic effect of etizolam, an anti-anxiety drug, on platelet-activating factor (PAF) was investigated in rabbit platelets in vitro. Etizolam inhibited PAF-induced aggregation in a dose-dependent manner, with an IC50 of 3.8 microM, about one tenth that of triazolam (IC50 = 30 microM). At 300 microM, it inhibited both ADP and arachidonic acid-induced aggregation only slightly, while the other anti-anxiety drugs tested had no effect on PAF-induced aggregation even at this concentration. Etizolam and triazolam inhibited the specific binding of 3H-PAF to PAF receptor sites on washed rabbit platelets with IC50 values of 22 nM and 320 nM, respectively. Diazepam and estazolam were inactive even at 1 microM. These results indicate that etizolam is a specific antagonist of PAF. PMID- 2890780 TI - Effects of catecholamines on isolated canine facial veins. AB - The buccal segment of the canine facial vein which was precontracted moderately with prostaglandin F2 alpha relaxed to different extents in response to dopamine (DA), norepinephrine (NE), epinephrine (Epi) and isoproterenol (Isp). Propranolol (10(-6) M) reversed the relaxation responses to contractions. In the presence of an alpha-adrenoceptor blockade and inhibitors of neuronal and extraneuronal uptakes, the four catecholamines relaxed the vein fully, and the order of pD2 values was Isp (8.34) greater than Epi (7.53) approximately equal to NE (7.50) much greater than DA (5.31). The results indicate that in the canine facial vein, beta-adrenoceptors predominate over alpha-adrenoceptors, and the subtype of beta adrenoceptor may be the beta 1-type. PMID- 2890781 TI - Effect of 5-(3-[4-(4-fluorophenyl)-1-piperazinyl]-propoxy)indan (BP-528) on benzodiazepine receptor bindings and gamma-aminobutyric acid release. AB - The action of a new type of anti-anxiety compound, 5-(3-[4-(4-fluorophenyl)-1 piperazinyl]-propoxy)indan (BP-528), was tested on benzodiazepine receptor bindings and on [3H]-GABA release. BP-528 did not alter [3H]-diazepam binding to rat cerebral cortical and hippocampal membranes either in the presence or absence of GABA; and the binding of [3H]-propyl-beta-carboline-3-carboxylate at low concentration (0.04 nM), which labels only the type I benzodiazepine receptor, was not changed by BP-528. BP-528 did not interact with the GABA-benzodiazepine receptor complex, which is related to the anti-anxiety activity of benzodiazepines. This compound affected neither GABA binding nor GABA uptake. Ten micromolar BP-528 depressed high K+-induced [3H]-GABA release from preloaded rat hippocampal slices. However, the same concentration of BP-528 also inhibited high K+-induced calcium uptake by rat cerebral cortical synaptosomes. PMID- 2890782 TI - Positive inotropic action of kappa opiate agonists, ethylketocyclazocine and dynorphin-A(1-13), in isolated rat atrium. AB - The effect of various opiate agonists on the contraction of isolated rat atrium was investigated. Ethylketocyclazocine (EKC) (30-100 microM) and dynorphin-A(1 13) (10-30 microM), which are kappa-type agonists, caused positive inotropic effects on electrically stimulated left atrium in a dose-dependent manner. In addition, EKC decreased the frequency of spontaneous beating in the right atrium. Morphine (mu-type), [Met5]- and [Leu5]-enkephalin (delta-type) did not affect both the developed tension and frequency of contractions. These results indicate that the positive inotropic action is specific for kappa-type opiate agonists. PMID- 2890783 TI - Effects of H2-receptor antagonists on 3H-cimetidine binding and histamine stimulation of cellular cAMP in isolated guinea pig gastric glands. AB - 3H-Cimetidine binding to plasma membranes of isolated guinea pig gastric glands was investigated, and the effects of five H2-receptor antagonists on 3H cimetidine binding and histamine stimulation of cellular cAMP were compared. Of the five cations tested, Cu++ markedly increased specific 3H-cimetidine binding. 3H-Cimetidine had high affinity (Kd = 0.41 x 10(-6) M) and low affinity (Kd = 12.8 x 10(-6) M) binding sites. Cimetidine and etintidine were potent inhibitors of 3H-cimetidine binding, while famotidine, ranitidine and TZU-0460 were not. Histamine stimulation of cellular cAMP was competitively inhibited by H2-receptor antagonists yielding pA2 values of 6.41 for cimetidine, 6.82 for etintidine, 6.87 for ranitidine, 6.94 for TZU-0460 and 7.60 for famotidine. Because the KB value (log KB = -pA2) of 0.39 x 10(-6) M for cimetidine is close to the Kd value for the high affinity 3H-cimetidine binding site, it is presumed to represent a part of the H2-receptor, and the relative potency of etintidine against cimetidine in inhibiting 3H-cimetidine binding is similar to that in inhibiting histamine stimulation of cellular cAMP. These results suggest that imidazole-derived H2 receptor antagonists (cimetidine and etintidine) and non-imidazole H2-receptor antagonists (famotidine, ranitidine and TZU-0460) compete with histamine at different sites on the H2-receptor of the gastric glands. PMID- 2890784 TI - [The effects of aorto coronary bypass grafting with the internal mammary artery- with special reference to the evaluation of left ventricular wall motion]. PMID- 2890785 TI - Enterotoxigenicity of heat-resistant and heat-sensitive strains of Clostridium perfringens. PMID- 2890786 TI - Comparison of two anti-Thy 1.1-abrin A-chain immunotoxins prepared with different cross-linking agents: antitumor effects, in vivo fate, and tumor cell mutants. AB - The A-chain of the plant toxin abrin was covalently linked to monoclonal anti-Thy 1.1 antibody (OX7) with the use of either N-succinimidyl-3-(2 pyridyldithio)propionate (SPDP) or 2-iminothiolane hydrochloride (2IT). The SPDP reagent generates a linkage containing a disulfide bond and an amide bond, whereas the 2IT reagent generates a linkage containing a disulfide bond and an amidinium bond. The two immunotoxins were powerfully and specifically toxic to Thy 1.1-expressing murine AKR-A lymphoma cells in vitro. Both reduced the rate of protein synthesis of the cells by 50% at a concentration of 10(-11) M. However, clonogenic assays revealed that about 1% of the AKR-A cells survived treatment with high concentrations of OX7-SPDP-abrin A, whereas only about 0.1% survived treatment with similar concentrations of OX7-2IT-abrin A. Several clones of the surviving cells were isolated. Of 11 clones of cells that had survived exposure to OX7-SPDP-abrin A, 10 were resistant to further treatment with OX7-SPDP-abrin A but had normal sensitivity to OX7-2IT-abrin A. These clones expressed moderate to high levels of the Thy 1.1 antigen and were fully sensitive to abrin. In contrast, all 10 clones of cells that had survived exposure to OX7-2IT-abrin A were substantially or entirely resistant to both immunotoxins. They expressed low to high levels of the Thy 1.1 antigen and were fully sensitive to abrin. The 2IT linked immunotoxin was much more effective than the SPDP-linked immunotoxin at protecting nu/nu mice against the growth of AKR-A lymphoma cells in the peritoneal site. A single iv injection of 0.3 nmol OX7-2IT-abrin A eradicated at least 99.99% of the tumor cells, as judged from the extension in the median survival time of the animals, whereas OX7-SPDP-abrin A eradicated only about 99% of the cells. The tumors that developed in the animals that received OX7-2IT abrin A were Thy 1.1-negative, whereas those in the recipients of OX7-SPDP-abrin A generally expressed normal levels of the Thy 1.1 antigen. The difference in antitumor activity of the immunotoxins was not due to differences in their in vivo fate, inasmuch as they were cleared from the bloodstream at an identical rate and broke down at the same rate to release free antibody.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2890787 TI - Tumor-host wasting not explained by adrenal hyperfunction in tumor-bearing animals. AB - This study addressed the question of whether hypercorticism in tumor-bearing animals contributes to the wasting of body fat and lean body mass, particularly that of skeletal muscles. For this purpose, hydrocortisone-substituted nongrowing sarcoma-bearing and control C57BL/6J mice were used that were either adrenalectomized or sham-operated prior to experimentation. Adrenalectomy in itself did not alter food intake or body composition in normal animals. Tumor bearing mice and pair-weighted control animals had elevated urinary excretion of corticosteroids compared with the urinary excretion in freely fed controls. The malignant tumor induced the well-recognized wasting in tumor-bearing animals, irrespective of the presence of the adrenal glands. Therefore, an elevated corticosteroid production did not account for the wasting of body fat, lean body mass, skeletal muscle proteins, or decreased RNA activity in quadriceps muscles from tumor-bearing animals, although such muscles were sensitive to physiologic doses of injected hydrocortisone (20 micrograms/day). Tyrosine aminotransferase (TAT) activity in liver tissue from tumor-bearing animals was higher than that induced by pharmacologic doses of hydrocortisone in normal animals. Physiologic doses of hydrocortisone induced hepatic TAT activity, but pair-weighed control animals with the same degree of hypercorticism as was found in tumor-bearing animals had normal TAT activity in liver tissue. Although hypercorticism is present in tumor-bearing animals, the results demonstrate that cancer cachexia can start and proceed independently of the adrenal glands. Therefore, adrenal hyperfunction is not the proximate cause for the development of experimental cancer cachexia induced by anorexia. PMID- 2890788 TI - [Principles of differentiated therapy of patients with hypertension of a benign course]. PMID- 2890789 TI - [Surgery of complicated forms of cryptorchism]. PMID- 2890790 TI - [Cryptorchism--current treatment principles]. PMID- 2890791 TI - [Treatment with betaxolol and placebo eyedrops in patients with glaucoma and reactive airway diseases]. AB - The study communicated here was designed to evaluate the absence of pulmonary beta-blockade as detected by a histamine provocation in betaxolol-treated patients suffering from open-angle glaucoma and coexisting obstructive airway disease. The study was a randomized, double-masked crossover trial, comparing betaxolol 0.5% ophthalmic solution and placebo. Ten patients (4 male, 6 female) were eligible by demonstrating baseline off-therapy IOP values exceeding 22 mmHg and a FEV1 value that was reduced by 15% to 20% following histamine provocation. After an appropriate washout period, baseline IOP and pulmonary function (FEV1, FVC) were tested. One drop of test medication (betaxolol or placebo) was instilled in both eyes; tonometry and a pulmonary function test were performed 90 minutes later. The patients then underwent a histamine provocation test. The concentration of histamine necessary to reduce FEV1 and FVC by 15% to 20% was recorded. The IOP was significantly reduced in patients treated with betaxolol, but not in those given placebo. FEV1 and FVC values 90 minutes after treatment with betaxolol or placebo were not significantly different from baseline values. After histamine provocation the FEV1 was, as expected, significantly decreased from baseline (15% to 20%) in both treatment groups. There was no statistical difference in the histamine concentration necessary to reduce the FEV1 by 15% to 20% between placebo (5.60 mg/ml) and betaxolol (5.25 mg/ml) treatments. This demonstrates that betaxolol has no pulmonary beta-blocking effect. Our study suggests that ophthalmic treatment with betaxolol in patients with glaucoma and obstructive airway disease enhances pulmonary safety due to the beta-1 cardioselective action of the drug. PMID- 2890793 TI - [Chronic pyelonephritis in patients with a history of hemorrhagic fever with nephrotic syndrome]. PMID- 2890792 TI - [Preoperative management of newborn infants with hyperinsulinemic hypoglycemia (2)]. AB - Four infants (three boys and one girl, ages 12-89 days) with persistent hyperinsulinism secondary to nesidioblastosis (two) or microadenoma of the pancreas (two) were treated with cyclic somatostatin (S) as part of the preoperative management until subtotal pancreatectomy was performed within 12 to 35 days. The individual dose dependent response of glucoregulatory hormones to exogenous was evaluated by means of the "somatostatin sensitivity test" (SST). Thereby S was infused in stepwise increasing doses, as dictated by the prevailing blood glucose levels, until normoglycemia was achieved concomitantly with a dextrose infusion at rates of 5 mg/kg/min. This procedure resulted only in a partial suppression of insulin, C-peptide, glucagon, HGH and cortisol, without recurrence of hypoglycemia. Compared to baseline levels, plasma concentrations of insulin decreased by 61%, of C-peptide by 64% and a rise of glucagon by 23% was observed. The SST which can be performed under routine clinical conditions, is a useful procedure for evaluating the individual S-dose necessary to achieve normoglycemia. The risk of total S-induced suppression of hormones, such as IRI, IRCP, HGH, glucagon and cortisol can be omitted. PMID- 2890794 TI - [Allergy in hemorrhagic fever with nephrotic syndrome]. PMID- 2890795 TI - Somatostatin and analogs lack splanchnic vasoconstrictive effects in anesthetized pigs. AB - Due to an apparently selective vasoconstrictive effect on the splanchnic circulation, somatostatin (SRIF) has been advocated for the treatment of variceal hemorrhage. The present study was designed to compare and contrast the systemic and splanchnic hemodynamic effects of SRIF and two of its long-acting analogs (SMS 201,995 and L 363,568) with those of Pitressin. Anesthetized pigs were subjected to laparotomy for placement of an electromagnetic flowmeter on the main trunk of the superior mesenteric artery (SMA). Systemic hemodynamic parameters of arterial blood pressure and cardiac output were monitored with thermodilution catheters. Portal venous blood was collected for measurement of plasma levels of SMS 201,995 and L 363,568 and for determination of gastrin levels during infusion of the latter analog. Experimental drugs were administered via an aortic cannula in a range (5-10 mg/kg bolus and 5-10 mg/kg/min continuous infusion) of dosages. At the higher dosages, SRIF, SMS 201,995, and L 363,568 decreased SMA blood flow (mean% +/- SD) 5.6 +/- 2.2, 1.6 +/- 4.4, and 8.0 +/- 3.8 after 10 min. None of the values achieved significance when compared to variation in baseline determinations. Pitressin (0.25 units, intravenously) produced a consistent and highly significant (P less than 0.001) reduction-in SMA flow after 5 min. Pharmacologic levels of SMS 201,995 and L 363,568 were reliably achieved in portal blood and the latter produced significant reduction (P less than 0.05) in portal venous levels of gastrin. SRIF and its long-acting analogs produced no significant splanchnic nor systemic hemodynamic effects in this model. PMID- 2890796 TI - Effects of oscillator frequency on phase-locking in the lamprey central pattern generator. AB - The central pattern generator (CPG) for locomotion can be thought of as a chain of segmental oscillators coupled together that produces the basic locomotor pattern. The isolated spinal cord of the lamprey is an excellent preparation in which to formulate general principles for the operation of the CPG. The stability of the preparation and the ease with which surgical lesions can be made in the cord have allowed the study of the coordinating system with a convenience unobtainable in more complex vertebrates. Mathematical models have been developed to help analyze the CPG and other systems of coupled oscillators. The models have pointed to two important parameters for determining the relative timing of a system of coupled oscillators: the nature of the coupling and the difference in frequency among the oscillators. The latter is dealt with here. In lampreys, the frequency differences of the segmental oscillators along the cord can be quite large. This factor is shown to be related to changes in the intersegmental phase lags during serotonin modulation of fictive swimming. An understanding of some effects of the frequency difference is also shown to have been important in helping to formulate a protocol for the demonstration of functional regeneration in the isolated spinal cord preparation. PMID- 2890797 TI - In vitro brainstem-spinal cord preparations for study of motor systems for mammalian respiration and locomotion. AB - Recently developed in vitro preparations of the brainstem-spinal cord from neonatal rat suitable for investigation of motor control systems for mammalian locomotion and respiration are described. The preparations remain viable for extended periods under standard in vitro conditions and generate rhythmic motor patterns for locomotion and respiration. The methodology of the preparations and characteristics of the motor output patterns are described. The preparations retain functional circuitry for major components of the motor control systems, including brainstem respiratory and spinal locomotor pattern generating networks, brainstem locomotor command regions, descending bulbospinal and ascending spinal pathways, and mechanosensory afferent input systems. They therefore offer potential for investigation of diverse aspects of the mammalian respiratory and locomotor control systems. PMID- 2890798 TI - Molecular biology in clinical haematology. PMID- 2890799 TI - [Salazopyrine and reactive arthritis]. PMID- 2890801 TI - Exploratory behavior and the dual activity of some psychoactive drugs. Part 1. AB - Animal behavior in a free environment involves the orienting reflex, a major component of which is exploratory behavior. Exploration is an essential, life preserving component of animal higher nervous functions and the experiments presented here show that exploratory behavior may differ according to the experimental subjects' emotional baseline. Exploratory performance may accordingly be affected differently by psychoactive drugs. PMID- 2890800 TI - [Preoperative treatment of hypoglycemia caused by an insulinoma with the somatostatin analog SMS 201-995]. PMID- 2890802 TI - [Treatment with neuroleptics is not dangerous for the patient. The risk of tardive dyskinesia is increased in overdosing]. PMID- 2890803 TI - [Use and abuse of benzodiazepines--a psychiatric and epidemiologic review]. PMID- 2890804 TI - [Experiences from a department of general psychiatry. Detoxication of patients with benzodiazepine dependence]. PMID- 2890805 TI - Protective activity of Vi capsular polysaccharide vaccine against typhoid fever. AB - The protective efficacy against typhoid fever of a single intramuscular injection of 25 micrograms of the Vi capsular polysaccharide (CPS) was assessed in a randomised double-blind controlled trial. Vaccination of 11,384 children was followed by 21 months' surveillance. 47 blood-culture-proven cases of typhoid occurred in children who received meningococcal A + C CPS vaccine and 19 cases in those vaccinated with Vi CPS. Protective efficacy was 60% calculated from the day of vaccination and 64% from 6 weeks after vaccination. Surveillance also included 11,691 unvaccinated children; 173 cases occurred in this group. Protective efficacy in relation to the unvaccinated group was 77.4% and 81.0% after 21 months, calculated immediately and 6 weeks after vaccination, respectively. Vaccination was associated with minimum local side-effects, and an increase in anti-Vi antibodies occurred, as measured by radioimmunoassay and enzyme-linked immunosorbent assay. Antibody levels remained significantly raised at 6 and 12 months post vaccination. Vi CPS is thus a safe and effective means of typhoid vaccination. PMID- 2890806 TI - Endogenous restoration of noradrenaline by precursor therapy in dopamine-beta hydroxylase deficiency. AB - DL-dihydroxyphenylserine was given by mouth in a single-blind, placebo-controlled trial to two patients with orthostatic hypotension due to dopamine-beta hydroxylase deficiency, in the hope of providing noradrenaline by endogenous decarboxylation. Dose-dependent increases in blood pressure were obtained over the range 150-600 mg. After 600 mg mean arterial pressure rose 33 and 19 mm Hg and these rises were tightly correlated with an increase in plasma noradrenaline (r = 0.995, p less than 0.001 and r = 0.88, p less than 0.05). Urinary noradrenaline increased from undetectable levels to 338 and 511 micrograms/24 h. Standing time (a correlate of functional capacity) also increased significantly in both patients. No side-effects were noted. PMID- 2890807 TI - Effect of unnatural noradrenaline precursor on sympathetic control and orthostatic hypotension in dopamine-beta-hydroxylase deficiency. AB - A patient with severe orthostatic hypotension due to dopamine-beta-hydroxylase deficiency was treated with the unnatural aminoacid D,L-threo-3,4 dihydroxyphenylserine (DOPS) in the hope that it would serve as a substrate of aromatic-L-aminoacid decarboxylase to produce (-)-noradrenaline. With a dose of 500 mg twice daily by mouth, blood pressure rose gradually from 100/55 to 145/85 mm Hg, and orthostatic hypotension disappeared. After 4 months' treatment the patient is free of symptoms and able to live a normal life. DOPS switched on the production of noradrenaline and reduced the excessive production of dopamine. During treatment plasma noradrenaline rose normally after standing and after infusion of tyramine, a biogenic amine that liberates stored neurotransmitter from sympathetic nerve terminals. These data demonstrate that in congenital dopamine-beta-hydroxylase deficiency dopamine instead of noradrenaline is released as the sympathetic neurotransmitter but that the integrity of the sympathetic neuron is otherwise intact. PMID- 2890808 TI - Interferons as mediators of psychiatric morbidity. An investigation in a trial of recombinant alpha-interferon in hepatitis-B carriers. AB - A significant increase in psychiatric morbidity, assessed by standard measures, was demonstrated in a group of patients receiving recombinant alpha-interferon for chronic hepatitis-B virus infection. In some cases the psychiatric symptoms were severe enough to need urgent psychiatric attention. The changes seemed most severe in patients with coexistent human immunodeficiency virus infection. The mental state changes are clinically reminiscent of those in the "post-viral" psychiatric syndromes. PMID- 2890811 TI - Psychiatric day hospitals for all? PMID- 2890809 TI - Effect of haem arginate therapy on porphyrin metabolism and mixed function oxygenase activity in acute hepatic porphyria. AB - The effect of haem arginate on porphyrin metabolism and haemoprotein function was studied during seven attacks of acute hepatic porphyria in 5 patients. In each attack it greatly reduced the overproduction of porphyrin precursors and repressed the overactivity of the rate-controlling enzyme of haem synthesis delta aminolaevulinic acid (ALA) synthase measured in leucocytes. Antipyrine clearance, an index of the oxidative function of cytochromes P-450, the major group of hepatic haemoproteins, was increased during haem therapy. Thus, haem arginate not only suppresses the overproduction of haem precursors but also improves hepatic oxidative metabolism in acute porphyria. PMID- 2890810 TI - Hepatocellular cancer: differences between high and low incidence regions. PMID- 2890812 TI - Cancer cytogenetics in clinical diagnosis. PMID- 2890813 TI - Intracerebral haematoma from aneurysm rupture: operation in moribund patients? PMID- 2890814 TI - Omeprazole. PMID- 2890815 TI - HIV infection: confidentiality for doctors. PMID- 2890816 TI - Infection today. PMID- 2890817 TI - Antiviral therapy. PMID- 2890818 TI - Interpreting survival rates for the treatment of decompensated diabetes: are we saving too many lives? AB - Discussion of the case of a patient admitted to hospital with decompensated diabetes revealed a conflict in attitudes to resuscitation of the patient from that disorder and from cardiac arrest. A survey was sent to 200 diabetologists and 200 cardiologists in the United Kingdom, asking about their management of diabetes and their therapeutic approaches to cardiac arrest for 3 elderly patients admitted with severe decompensated diabetes. The response rate was poor (27%) but the answers showed that all 3 patients were more likely to be resuscitated from decompensated diabetes than from cardiac arrest. Possible reasons for a different approach to the two conditions are discussed, and suggestions are put forward for a greater involvement by patients in decisions about future resuscitation. PMID- 2890819 TI - Geographical and secular trends in stroke incidence. PMID- 2890820 TI - Effects of sleeping with the bed-head raised and of ranitidine in patients with severe peptic oesophagitis. AB - Sleeping with the bed-head raised is commonly recommended as treatment for patients with troublesome oesophagitis, but its effect has not been objectively tested. Ranitidine therapy is useful in oesophagitis, but it does not often produce complete relief of symptoms. The effects of each of these treatments alone and in combination have been studied in 71 patients with severe (grade III) peptic oesophagitis. Each treatment improved both symptoms and endoscopic appearances significantly more than placebo did. However, the combination of the two treatments was much better than either alone; the reduction in pain score and the area of ulceration healed were about twice those with either treatment alone. Smoking more than five cigarettes per day or drinking more than 30 g alcohol per day significantly reduced the effectiveness of ranitidine therapy, but age, sex, body weight, or the presence of a hiatus hernia had no detectable effect. PMID- 2890821 TI - Screening for neuroblastoma. PMID- 2890822 TI - Non-steroidal anti-inflammatory drugs, plasma half-lives, and adverse reactions. PMID- 2890823 TI - Increasing frequency of adult IgA nephropathy in the UK? PMID- 2890824 TI - Full-spectrum classroom light and sickness in pupils. PMID- 2890825 TI - Blood aluminium levels in preterm infants fed parenterally or with cows' milk formulae. PMID- 2890826 TI - How liquorice works. PMID- 2890827 TI - Spironolactone and hyperkalaemia in patients with impaired renal failure. PMID- 2890828 TI - Potential analgesic contribution from morphine-6-glucuronide in CSF. PMID- 2890829 TI - Sewage pollution of bathing water. PMID- 2890830 TI - Main line sewage. PMID- 2890831 TI - Safety of pasteurised milk. PMID- 2890832 TI - Salmonella and food handlers. PMID- 2890833 TI - Erythrocyte crenation, myocardial damage, and free fatty acids. PMID- 2890834 TI - Pain, anaesthesia, and babies. PMID- 2890835 TI - Haemorrhagic fever with renal syndrome in a case in northern Albania. PMID- 2890837 TI - Conservation of smallpox virus. PMID- 2890836 TI - Meningococcal disease due to group A Neisseria meningitidis in contacts of Mecca pilgrims. PMID- 2890838 TI - HIV and the pancreas. PMID- 2890839 TI - False-positive anti-HIV tests and blood donation. PMID- 2890840 TI - HIV antigen screening in blood donors. PMID- 2890841 TI - Borrelia infection and presenile dementia. PMID- 2890842 TI - Epithelioid angiomatosis: a variant of Kaposi's sarcoma. PMID- 2890843 TI - Central obesity and coronary heart disease in men. PMID- 2890844 TI - Facial cooling and perception of dyspnoea. PMID- 2890845 TI - Medical care at Brixton Prison. PMID- 2890846 TI - Investigation of sexual abuse. PMID- 2890847 TI - Should the dose of hepatitis B vaccine be reduced in newborn babies? PMID- 2890848 TI - Increased nigral iron content in postmortem parkinsonian brain. PMID- 2890849 TI - Pyriformis syndrome. PMID- 2890850 TI - T-lymphocyte alveolitis in HTLV-I-associated myelopathy. PMID- 2890851 TI - Confidentiality for doctors who are HIV positive. PMID- 2890852 TI - Improvement in the haemostatic defect of uraemia after treatment with recombinant human erythropoietin. AB - Patients with uraemia have a defect of primary haemostasis expressed as long skin bleeding times and reduced platelet adhesion to the arterial subendothelium. Transfusion of red cells shortens the bleeding time and stops bleeding symptoms in uraemia. This study investigated whether the efficacy of recombinant human erythropoietin in correcting anaemia and the improvement in haemostasis are correlated. Recombinant human erythropoietin was given to seven consecutive patients with chronic uraemia, a history of bleeding, severe anaemia (haematocrit below 23%), and long bleeding times (above 19 min). The progressive rise in haematocrit induced by increasing doses of recombinant human erythropoietin was paralleled by a pronounced shortening of the bleeding time. Platelet adhesion to the subendothelium of human umbilical arteries, very low before the study, increased greatly in all patients and became normal in six. None of the patients bled during the study period. PMID- 2890853 TI - Evidence for tumour necrosis factor/cachectin production in cancer. AB - Labile tumour-necrosis-factor-like (TNF) activity was detected by means of an enzyme-linked immunosorbent assay in 50% of 226 freshly obtained serum samples from cancer patients with active disease. In contrast, only 3% of 32 samples from normal subjects and 18% of 39 samples from cancer patients with no clinically evident disease were positive for this factor, with low levels of activity. Greater proportions of serum samples from patients with ovarian or oat-cell carcinoma were positive (69% and 63%) than those from patients with lymphoma (26%). RNA preparations from peripheral-blood mononuclear cells and solid tumours were probed with TNF complementary DNA; evidence of TNF messenger RNA was found in 8 of 11 samples of peripheral-blood mononuclear cells from cancer patients, but only 1 of 8 normal subjects, and in 2 of 6 colorectal tumours. As yet the inducing stimulus and the clinical significance of TNF production in cancer are not understood. PMID- 2890854 TI - Effects of combined pancreatic and renal transplantation on diabetic neuropathy: a two-year follow-up study. AB - To investigate whether diabetic neuropathy can be reversed after pancreatic transplantation 13 diabetic patients were examined by means of conventional electroneurography and tests on autonomic function before and 6, 12, and 24 months after combined renal and pancreatic transplantation. 15 diabetic patients receiving a kidney graft only and 15 non-diabetic kidney graft recipients served as controls. Before transplantation neuropathy was most advanced in the two diabetic groups. Both diabetic groups showed a similar slight but significant improvement of nerve conduction after transplantation. In the non-diabetic group nerve conduction became essentially normal. No group showed improvement in autonomic dysfunction. The improvement in nerve conduction after combined kidney and pancreas transplantation was most probably due to the elimination of uraemia. Furthermore, 2 years of normoglycaemia did not reverse the diabetic neuropathy to an important extent at this late stage of the disease. PMID- 2890855 TI - Potential of urinary neopterin excretion in differentiating chronic non-A, non-B hepatitis from fatty liver. AB - Urinary neopterin excretion was measured in 26 patients with histologically proven chronic non-A, non-B hepatitis (16 chronic persistent hepatitis, 10 chronic active hepatitis) and in 16 patients with steatosis. The potential of neopterin levels to discriminate between the two patient groups was compared with that of standard laboratory variables. Neopterin levels and triglycerides were shown to be the best variables for discriminating between the hepatitis and fatty liver patients, neopterin being the more specific of the two. Neopterin excretion in chronic persistent hepatitis was not statistically different from that in chronic active hepatitis. In the absence of specific tests, increased neopterin excretion seems to be a useful marker for diagnosing chronic non-A, non-B hepatitis and particularly in differentiating it from fatty liver. PMID- 2890856 TI - Ultrasonic assessment of complications during first trimester of pregnancy. AB - 624 women were referred to an emergency gynaecological ultrasound clinic with a provisional diagnosis of threatened miscarriage based on a history of amenorrhoea and vaginal bleeding with or without abdominal pain. High-resolution abdominal sector scanning was used to assess fetal size and viability, as well as uterine and placental size, to identify features which might indicate imminent fetal death. In 158 women there was no evidence of pregnancy; 60 women had an ectopic pregnancy. In the remaining 406 women ultrasound examination correctly identified the underlying cause of vaginal bleeding at first presentation in all but the 6 who subsequently aborted. 3.9% of the patients had a second empty sac and 5.4% had an intrauterine haematoma; none of these women subsequently aborted. 2 patients had early-onset oligohydramnios and spontaneous abortion occurred in both. PMID- 2890857 TI - Specific interleukin-1 inhibitor in serum and urine of children with systemic juvenile chronic arthritis. AB - Interleukin-1 (IL-1) activity and inhibition were studied in serum and urine from nine patients with systemic juvenile chronic arthritis (S-JCA). In afebrile patients IL-1 activity was normal or high. Serum from two afebrile S-JCA patients taken during a period of severe disease activity had an enhancing effect on the activity of exogenous IL-1. Secondary amyloidosis subsequently developed in one of these patients. In contrast, in febrile patients' serum and urine IL-1 activity was low, apparently reflecting the presence of a strong inhibitor of IL 1 activity measured by the inhibition of prostaglandin E2 production by synovial cells. This inhibition was greatest at the time of peak temperature, suggesting the possibility of feedback regulation during fever. This novel identification in S-JCA of a specific IL-1 inhibitor that competes at the IL-1 receptor level may be an important step in the understanding of the pattern of fever and the evaluation of disease in patients with S-JCA. PMID- 2890858 TI - Consequences of new radiation dosimetry. PMID- 2890859 TI - Syndrome X. PMID- 2890860 TI - Transplantation for acute liver failure. PMID- 2890861 TI - Dying for a drink. PMID- 2890862 TI - Traumatic corneal abrasion. PMID- 2890863 TI - Antimicrobial agents: a widening choice. PMID- 2890864 TI - A population-based evaluation of sustained mechanical ventilation of newborn babies. AB - The scope and impact of sustained assisted ventilation were investigated within a cohort of 11,061 babies born to a geographically defined community. 76 (0.7%) normally formed newborn infants and 3 with major anomalies had respiratory failure potentially treatable by mechanical ventilation. 31 (0.3%) weighed less than 1000 g. 28 infants underwent more than 8 hours' assisted ventilation, which was initiated as an emergency in 14 cases, as an elective measure to minimise the hazards of transport in 10, and as a therapeutic option for apnoea in 4. Pneumothorax requiring drainage complicated the ventilation of 10 infants, 7 of whom died and 2 were subsequently disabled. Of the 14 ventilated survivors examined at school age, 2 had serious persisting disabilities associated with the ventilation and 2 with other perinatal events; of the 10 considered normal, 5 had had emergency ventilation. PMID- 2890865 TI - Role of the pharmaceutical industry in major clinical trials. PMID- 2890867 TI - WHO consultation on prevention and control of AIDS in prisons. PMID- 2890866 TI - AIDS in prison. AB - A survey carried out in 17 countries on behalf of the Council of Europe shows how prison doctors and administrations have reacted to the AIDS epidemic in ways that are not always scientifically and ethically sound. The pressing need to control HIV infection in prison, to counsel and support seropositive prisoners, to care for prisoners who get AIDS, and to cope with the psychosocial pressures within a closed, authoritarian environment pose a serious challenge to prison medical services; it is far from certain that they have sufficient resources and professional independence to cope. Failure to react adequately to the AIDS epidemic in prisons would have serious consequences both for the community as a whole and for the ethical position of prison doctors. PMID- 2890869 TI - Carcinoma-in-situ of testis in patients with assumed extragonadal germ-cell tumours. PMID- 2890868 TI - Alleviation of motion sickness by nifedipine. PMID- 2890871 TI - Pseudopolycythaemia. PMID- 2890870 TI - Gender verification of female athletes. PMID- 2890872 TI - Awareness of hypoglycaemia in diabetes. PMID- 2890873 TI - Oral contraceptives and breast cancer. PMID- 2890874 TI - 6-Mercaptopurine dosage. PMID- 2890875 TI - What makes some children shortsighted? PMID- 2890877 TI - Post-streptococcal glomerulonephritis. PMID- 2890876 TI - "Superwarfarin" (bromodialone) poisoning in two children resulting in prolonged anticoagulation. PMID- 2890878 TI - Is atrial distension the physiological stimulus for release of atrial natriuretic peptide? PMID- 2890879 TI - Immunological mechanisms of cyclosporin in skin allograft. PMID- 2890880 TI - Colchicine myoneuropathy. PMID- 2890882 TI - Nursing position of babies delivered by caesarean section. PMID- 2890881 TI - Prenatal diagnosis of congenital adrenal hyperplasia. PMID- 2890883 TI - Cycad use and motor neurone disease in Irian Jaya. PMID- 2890884 TI - Detection of relapse in acute lymphoblastic leukaemia by cusum analysis of peripheral blood-count. PMID- 2890885 TI - Safety of equine rabies immune globulin. PMID- 2890886 TI - DNA probes which unambiguously distinguish Taenia solium from T saginata. PMID- 2890887 TI - Ploidy as prognostic determinant in lung cancer. PMID- 2890888 TI - HIV testing on all pregnant women. PMID- 2890889 TI - Is infection with HIV a risk factor for cervical intraepithelial neoplasia? PMID- 2890890 TI - Breast-feeding and HIV infection. PMID- 2890891 TI - Thrombolysis at home. PMID- 2890892 TI - Duodenal ulcer incidence. PMID- 2890893 TI - Clostridium septicum and neutropenic enterocolitis. PMID- 2890894 TI - Duodenal ulcers in childhood. PMID- 2890895 TI - Mortality and Clostridium difficile diarrhoea in the elderly. PMID- 2890896 TI - Is antipaternal cytotoxic antibody a valid marker in the management of recurrent abortion? PMID- 2890897 TI - Lactitol, lactulose, and blood ammonia. PMID- 2890898 TI - H2-receptor antagonist non-responders. PMID- 2890899 TI - Courtroom science and standards of proof. PMID- 2890900 TI - Controlled trial of endoscopic sclerosis in bleeding peptic ulcers. AB - Of 113 patients in whom endoscopy revealed a bleeding gastric or duodenal ulcer 55 were randomly allocated to receive endoscopic sclerosis (ES) (injections of adrenaline/polidocanol) plus cimetidine while 58 received cimetidine alone as controls. 3 patients treated with ES (5.5%) compared with 25 controls (43.1%) had a major recurrent haemorrhage during their hospital stay. ES also led to significant reductions in the need for emergency surgery (3 vs 20 patients), transfusion requirements (mean 0.42 [SD 1.1] vs 2.7 (3.19) U), and the length of hospital stay (11.6 [5.1] vs 16.2 [11.3] days). ES as an adjunct to conventional medical treatment is an effective and safe emergency therapy for gastrointestinal bleeding due to peptic ulcer. PMID- 2890901 TI - Effective strategy for prenatal prediction of Duchenne and Becker muscular dystrophy. AB - Deletions in the gene sequence for Duchenne (DMD) and Becker (BMD) muscular dystrophy were detected in affected males with four cDNA probes, Cf56a, Cf23a, Ca1A, and Cf27. Most of the deletions were seen with only one of the probes. Cf23a detected all BMD deletions seen with Cf56a and some that were not. The same markers also detected restriction fragment length polymorphisms for those cases where deletions were not evident. The probes were also used successfully for prenatal diagnosis in two families each with two DMD affected males. In DMD families successive application of probes Cf56a, Ca1A, and Cf27 will give a 70% chance of detecting the mutation. BMD families should first be screened with the Cf23a probe. PMID- 2890902 TI - Fetal breathing movements are not a reliable predictor of continued lung development in pregnancies complicated by oligohydramnios. AB - Fetal breathing activity was monitored by ultrasonography in 14 patients with oligohydramnios (4 with fetal anuria and 10 with premature rupture of the membranes). 45 patients with intact membranes, with normal amniotic fluid volume, and matched for gestational age were the controls. Fetal breathing movements were seen in all 8 patients who died in the perinatal period with a necropsy diagnosis of lung hypoplasia. While patients with premature rupture of the membranes (irrespective of outcome) spent the same or less time breathing than controls, fetuses with renal anomalies, oligohydramnios, and lung hypoplasia spent more time breathing than controls. The observation of fetal breathing activity is not helpful in identifying patients with oligohydramnios at risk of lung hypoplasia. PMID- 2890903 TI - Glucagon-like peptide-1 7-36: a physiological incretin in man. AB - The physiological role of glucagon-like peptide-1 7-36 amide (GLP-1 7-36) in man was investigated. GLP-1 7-36-like immunoreactivity was found in the human bowel; its circulating level rose after oral glucose and after a test breakfast. When it was infused into seven volunteers at a rate to mimic its postprandial plasma concentration in the fasting state, plasma insulin levels rose significantly and glucose and glucagon concentrations fell. During an intravenous glucose load, it greatly enhanced insulin release and significantly reduced peak plasma glucose concentrations, compared with a control saline infusion, even inducing postinfusion reactive hypoglycaemia. By comparison, infusion of glucose-dependent insulinotropic peptide (GIP) to physiological levels was less effective in stimulating insulin release. These observations suggest that GLP-1 7-36 is a physiological incretin and that it is more powerful than GIP. The observation of greatly increased postprandial plasma GLP-1 7-36 levels in patients with postgastrectomy dumping syndrome suggests that it may mediate the hyperinsulinaemia and reactive hypoglycaemia of this disorder. PMID- 2890905 TI - Primary health care: government's worthy words amid the gloom. PMID- 2890904 TI - Reduced in-vitro susceptibility to mefloquine in West African isolates of Plasmodium falciparum. AB - West African isolates of Plasmodium falciparum were more susceptible to chloroquine but less susceptible to mefloquine than were Southeast Asian isolates. The West African isolates were more sensitive to halofantrine than to mefloquine. Since neither mefloquine nor halofantrine has been used in West Africa, the findings suggest that P falciparum may be inherently resistant to mefloquine and that mefloquine should be introduced cautiously to West Africa. Moreover, halofantrine may be of greater value than mefloquine for controlling multidrug-resistant falciparum malaria in West Africa. PMID- 2890906 TI - Mifepristone--contragestive agent or medical abortifacient? PMID- 2890907 TI - Progress in management of epididymitis? PMID- 2890908 TI - Human embryo research: vote for progress. PMID- 2890909 TI - New shoulders for old. PMID- 2890910 TI - Renal transplantation and the skin. PMID- 2890911 TI - Is "improvement" real with percutaneous transluminal angioplasty in the management of renovascular hypertension? AB - 58 hypertensive patients with suspected renovascular disease underwent renal arteriography, and 29 (52%) were found to have renovascular disease. Percutaneous transluminal angioplasty was technically successful in 14 (50%) of the 29. The effect on blood pressure was assessed over 20 months. Technically successful transluminal angioplasty led to cure of hypertension in 4 patients (29%) and "improvement" in 5 (36%). However, "improvement" occurred spontaneously in 8 (32%) of the 25 patients found on arteriography not to have renovascular disease and who received no intervention. This suggests that reported improvement after transluminal angioplasty may be spurious and that the true benefit of the procedure can be assessed only from the cure rate. About 50% of patients with fibromuscular renovascular disease are cured of their hypertension but only about 8% of patients with atherosclerotic renovascular disease benefit from the procedure. PMID- 2890912 TI - Aberrations of normal development and involution (ANDI): a new perspective on pathogenesis and nomenclature of benign breast disorders. AB - A framework for understanding and management of benign breast disorders is presented, based on the notion that most breast complaints can be explained as minor aberrations of the normal processes of development, cyclical change, and involution. The generic term ANDI (aberrations of normal development and involution) is introduced to allow breast problems to be placed within an overall framework of pathogenesis; this concept also permits more detailed individual assessment with respect to normality and disease. Fibrocystic disease and its synonyms are discarded in favour of terms that are strictly descriptive of the clinical and/or histological picture. PMID- 2890913 TI - Clinical use of the quinolones. PMID- 2890914 TI - Delta hepatitis. PMID- 2890915 TI - Treatment with ursodeoxycholic acid renders children with biliary atresia suitable for liver transplantation. PMID- 2890917 TI - Passive smoking and chronic obstructive lung disease. PMID- 2890916 TI - Leukaemia near Massachusetts nuclear power plant. PMID- 2890918 TI - Immunisation of the preterm baby. PMID- 2890919 TI - Which transformation for normalising skinfold and fatness distributions? PMID- 2890920 TI - Pasini's regional jejunitis. PMID- 2890921 TI - LFA-1, LFA-3, and ICAM-1 expression in Burkitt's lymphoma. PMID- 2890922 TI - Isolation of hepatitis A virus from polluted river water on FRP/3 cells. PMID- 2890923 TI - Prediction of onset of pre-eclampsia in patients with pregnancy-induced hypertension by continuous-wave Doppler ultrasound. PMID- 2890924 TI - Leuconostoc, an emerging vancomycin-resistant pathogen. PMID- 2890925 TI - Factor XII deficiency associated with loin pain/haematuria syndrome. PMID- 2890926 TI - Rett's syndrome and ornithine carbamoyltransferase deficiency. PMID- 2890927 TI - Absence of parvovirus and cytomegalovirus in red-cell aplastic crises in glucose 6-phosphate dehydrogenase deficiency. PMID- 2890928 TI - Fatness and the energy cost of carrying loads in African women. PMID- 2890929 TI - HIV-1 seroprevalence and AIDS diagnostic criteria in Central African Republic. PMID- 2890930 TI - Lactulose and ammonia. PMID- 2890931 TI - Zidovudine for lymphocytic interstitial pneumonitis in AIDS. PMID- 2890932 TI - Good intentions, unfortunate consequences. PMID- 2890933 TI - Responsibility and illness. PMID- 2890934 TI - Sociology and medicine. PMID- 2890935 TI - Continuum of psychosis. PMID- 2890936 TI - Genetics training for doctors. PMID- 2890937 TI - Pica, paper, and porphyria. PMID- 2890939 TI - Vancomycin-associated lacrimation. PMID- 2890938 TI - Time course of cyclosporin/itraconazole interaction. PMID- 2890940 TI - Zygomycetic gangrenous cellulitis. PMID- 2890941 TI - Naturally occurring gastritis associated with Campylobacter pylori infection in the rhesus monkey. PMID- 2890942 TI - Shunt treatment for fetal obstructive uropathy. PMID- 2890943 TI - Diploid cell rabies vaccine, six doses or five? PMID- 2890944 TI - Osteoporosis research: a new direction? PMID- 2890945 TI - Erythromycin and gastrointestinal motility. PMID- 2890946 TI - Importing khat, legal but dangerous. PMID- 2890947 TI - Adverse reactions to duplex scanning. PMID- 2890948 TI - Surgical retrieval of epididymal spermatozoa. PMID- 2890949 TI - An attempt to remedy through the courts a lack of NHS facilities. PMID- 2890950 TI - Draft legislation on infertility services and embryo research. PMID- 2890951 TI - The European Stroke Prevention Study (ESPS). Principal end-points. The ESPS Group. AB - In a multicentre double-blind trial, 2500 patients with a clinical diagnosis of a recent cerebrovascular event of atherothrombotic origin (transient ischaemic attack, reversible ischaemic neurological deficit, or stroke) were randomised to receive either dipyridamole 75 mg plus acetylsalicylic acid 325 mg (DP-ASA, 1250 patients) or placebo (1250 patients) thrice daily. Follow-up was twenty-four months. On intention-to-treat analysis, 473 patients reached an end-point (stroke or death from any cause), 190 on DP-ASA and 283 on placebo. Survival curves for end-points showed 33% benefit in favour of the DP-ASA group (p less than 0.001). 108 patients died in the DP-ASA group and 156 in the placebo group (p less than 0.01). Results of an explanatory analysis were similar. PMID- 2890952 TI - Improved early diagnosis of adult polycystic kidney disease with flanking DNA markers. AB - A new polymorphic DNA marker for the diagnosis of autosomal dominant adult polycystic kidney disease (APKD) has been identified. The new marker, 24-1, flanks the APKD gene on the side opposite to the alpha globin on the short arm of chromosome 16. When both DNA polymorphisms bracketing the gene are informative the reliability of prenatal and presymptom diagnosis of polycystic kidney disease in non-recombinants (92% of cases) is more than 99%. PMID- 2890954 TI - Negligible sublingual absorption of nifedipine. AB - The sublingual absorption of nifedipine was investigated in 11 healthy volunteers. After the subjects bit a capsule containing 10 mg nifedipine in solution and did not swallow for 20 min (at which time the mouth was washed out), absorption was slow and led to low plasma levels (median 10 ng/ml). After the same subjects bit and swallowed a capsule, absorption was faster and higher plasma levels were achieved 982 ng/ml). Biting a capsule and swallowing its contents is recommended in cardiovascular emergencies. PMID- 2890953 TI - Outbreak of fever caused by Streptobacillus moniliformis. AB - A large outbreak of streptobacillary fever, confirmed by the isolation of Streptobacillus moniliformis from blood culture, affected 304 people, 43% of the total population of 700 in a boarding school. Raw milk initially appeared to be the vehicle of infection, but detailed epidemiological investigation showed significant statistical associations between the development of illness and the consumption of both milk and water. Further analysis showed that the association with water was independent of that with milk and that water was therefore more likely to have been the vehicle of infection. Opportunity for contamination of water by rats existed, although contamination was not confirmed by the isolation of S moniliformis from either rats or the water supply. PMID- 2890955 TI - Spinal cord degeneration in divers. AB - Spinal cords from 8 professional and 3 amateur divers who died accidentally were examined histopathologically. Marchi-positive degeneration was found in the cords of 3 professional divers, variously affecting the posterior, lateral, and to a lesser extent the anterior columns. In 1 there was degeneration of afferent fibres within the posterior columns. PMID- 2890956 TI - Accounting for perioperative deaths. PMID- 2890957 TI - Anaemia in premature infants. PMID- 2890958 TI - Sudden-onset strabismus in childhood. PMID- 2890959 TI - Tumoral calcinosis. PMID- 2890960 TI - Epilepsy and headache. PMID- 2890962 TI - Bacterial diarrhoea and its treatment. PMID- 2890961 TI - Fetal heart rate monitoring during labour--too frequent intervention, too little benefit? AB - For many obstetricians and midwives continuous electronic fetal heart rate monitoring during labour has replaced the traditional method of intermittent auscultation. Of the eight prospective randomised controlled trials designed to assess its value in obstetric care, four were concerned with mothers defined as being at high-risk, three with normal or low-risk patients, and the eighth with the total population of a maternity hospital over several months. None suggested any major advantage of continuous fetal heart rate monitoring over intermittent surveillance in terms of neonatal mortality, morbidity, cord blood pH values, or the five minute Apgar score. The rates of caesarean section and forceps delivery were higher in the continuously monitored group. For low-risk mothers there is a good case for a return to the traditional method of intermittent auscultation with its lower false-positive rate, lesser incidence of intervention, and opportunity for greater contact between the maternity care staff and the mother. PMID- 2890963 TI - Leucocyte typing--OKCD? PMID- 2890965 TI - International Physicians for the Prevention of Nuclear War. A glance back and a look at the future. PMID- 2890964 TI - Lessons from the confidential enquiry into perioperative deaths in three NHS regions. PMID- 2890966 TI - International Physicians for the Prevention of Nuclear War. Some personal reflections. PMID- 2890967 TI - Lysis of basilar artery occlusion with tissue plasminogen activator. PMID- 2890968 TI - Remission of Crohn's disease with antimycobacterial chemotherapy. PMID- 2890969 TI - Congenital malformations after in-vitro fertilisation. PMID- 2890971 TI - Scrotal ultrasonography. PMID- 2890970 TI - Relapse after autografting with peripheral blood stem cells. PMID- 2890972 TI - HTLV-I-associated spastic paraparesis in an Italian woman. PMID- 2890973 TI - Asbestos exposure and carcinoma of penis. PMID- 2890974 TI - Atrial natriuretic peptide, blood pressure, and age. PMID- 2890976 TI - Psychiatric disturbances in patients with dyspepsia of unknown cause. PMID- 2890975 TI - Podophyllin/podophyllotoxin. PMID- 2890977 TI - Child sexual abuse. PMID- 2890978 TI - An apparent homozygous X-linked disorder with carbohydrate-deficient serum glycoproteins. PMID- 2890979 TI - Non-steroidal anti-inflammatory drugs and perforated peptic ulcer. PMID- 2890980 TI - Screening test for ataxia telangiectasia. PMID- 2890981 TI - HLA genes and longevity. PMID- 2890982 TI - Air conditioning and disease. PMID- 2890983 TI - Anaesthesia, teeth, and litigation. PMID- 2890984 TI - Crisis in the NHS. PMID- 2890985 TI - More magnetic resonance scanners? PMID- 2890987 TI - AIDS and medical ethics. PMID- 2890986 TI - Intraprofessional competitive prescribing for the drug addict. PMID- 2890988 TI - Latency preceding seroconversion in sexually transmitted HIV infection. PMID- 2890989 TI - Bisexuality, a risk factor for HIV infection in military men. PMID- 2890990 TI - Radiation, cancer risk, and the new dosimetry. PMID- 2890991 TI - Radiation experiments on British soldiers. PMID- 2890992 TI - Ten-day rule. PMID- 2890993 TI - Monitoring oestradiol implantation. PMID- 2890994 TI - Mifepristone (RU 486) and second-trimester termination. PMID- 2890995 TI - Benzodiazepine overconsumption in pregnancy. PMID- 2890996 TI - A policy on benzodiazepines. PMID- 2890997 TI - Simplified method for evaluating proximal tubular fluid reabsorption. PMID- 2890998 TI - Cytomegalovirus pneumonitis. PMID- 2890999 TI - Ribavirin. PMID- 2891000 TI - Treatment of multiresistant Salmonella typhi with oral ciprofloxacin. PMID- 2891001 TI - Screening for fetal and genetic abnormality. PMID- 2891003 TI - [Anamnesis and findings in expert assessment]. PMID- 2891002 TI - Assisted reproduction and selective reduction of pregnancy. PMID- 2891004 TI - [Borderline syndrome and its significance in expert assessment]. PMID- 2891005 TI - [HDL diagnosis]. PMID- 2891006 TI - [Preventive health exemplified by preventive cardiology]. PMID- 2891007 TI - [Prognosis, periods of hospitalization and work disability in type I diabetes mellitus]. PMID- 2891008 TI - [Incidence and mortality of malignant neoplasms. An analysis of Saarland data 1979-1984]. PMID- 2891009 TI - [Regional distribution of mortality of cancer patients in the Hamburg city district 1970-1972 and its comparison with the distribution 1960-1962]. PMID- 2891010 TI - [AIDS and life insurance. Considerations of insurability from the medical viewpoint]. PMID- 2891011 TI - Subcellular distribution of dynorphin-like immunoreactivity in rat adenohypophysis in comparison with luteinizing hormone and follicle-stimulating hormone. AB - Dynorphin and other proenkephalin B-derived peptides exist in the rat adenohypophysis in high concentrations and may have important roles in endocrine function. At the cellular level, dynorphin peptides are colocalized with the gonadotropins in at least a subpopulation of gonadotrophs. In this study dynorphin-containing particles were compared with secretory granules containing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by means of differential centrifugation and sucrose density gradient centrifugation. When anterior pituitary homogenate of male rats was subjected to differential centrifugation, about 70% of both dynorphin- and LH-containing particles sedimented at 30,000 x g. LH granules and dynorphin-containing particles comigrated in continuous sucrose density gradients both under nonequilibrium conditions as well as when equilibrium was attained. FSH storage granules were found to sediment in slightly denser fractions, with substantial overlap. Hence, dynorphin-containing particles and gonadotropin-containing granules exhibit similar characteristics. These hormones may, therefore, be colocalized also at the subcellular level or stored in separate but similar vesicles. PMID- 2891012 TI - Adrenergic receptors are not mediators in the lipolytic effect of somatostatin in rat adipocytes. AB - Beta-adrenergic receptors have been purported to act as possible mediators in the lipolytic effect of somatostatin in vivo. Investigations with isolated rat adipocytes studying the lipolytic activity of somatostatin (1.7 x 10(-7) M), glucagon (8.1 x 10(-8 M) and norepinephrine (10(-6) M), have shown that the lipolytic effect stimulated by somatostatin is not altered by 10(-5) M propranolol (beta-antagonist); is significantly enhanced by 10(-5) M isoproterenol (beta-agonist) and is not altered by the addition of 10(-6) M phenoxybenzamine (alpha-antagonist) or 10(-6) M phenylephrine (alpha-agonist). Similar results were found when lipolysis was stimulated by glucagon, whereas the lipolytic effect stimulated by norepinephrine was blocked by propranolol. These results indicate that the direct lipolytic effect of somatostatin on isolated rat adipocytes does not seem to be mediated through mechanisms involved with adrenergic receptors. PMID- 2891014 TI - Myocardial flow and function after regional beta-blockade in exercising dogs. AB - This study was designed to examine the contribution of beta 1- and beta 2 adrenergic receptors in modulating coronary blood flow and cardiac function in exercising dogs. Dogs were chronically instrumented to measure left circumflex flow velocity (CFV), heart rate, regional left ventricular function [systolic shortening, (%S) and maximum velocity of shortening (dL/dt(s)max)], and global left ventricular function [left ventricular pressure (LVP and dP/dtmax)]. Exercise significantly increased LVP (31 +/- 4%), dP/dtmax (130 +/- 17%), heart rate (116 +/- 20%), %S (28 +/- 6%), dL/dt(s)max (89 +/- 23%), and CFV (91 +/- 25%). Regional injection of the non-selective beta-blocker propranolol (1.0 mg) into the circumflex artery during exercise was associated with decreases in LVP ( 8 +/- 3%), dP/dtmax (-17 +/- 3%), %S (-15 +/- 4), dL/dt(s)max (-13 +/- 4%), and CFV (-22 +/- 4%). Selective beta 1-receptor blockade with atenolol (1.0 mg, i.c.) was associated with similar decreases in LVP (-7 +/- 3%), dP/dtmax (-33 +/- 4%), %S (-12 +/- 3%), dL/dt(s)max (-17 +/- 2%), and CFV (-18 +/- 3%) during exercise. In contrast, selective beta 2-receptor blockade with ICI 118551 (250 micrograms, i.c.) produced significant decreases in only CFV (-11 +/- 2%) during exercise. Thus, the data suggest that the reductions in myocardial contractile function and flow after regional beta-blockade are primarily due to a decrease in myocardial beta 1-receptor stimulation. In addition, there apparently is a small involvement of either coronary vascular or pre-synaptic beta 2-receptors in mediating the coronary vascular flow response during exercise. PMID- 2891013 TI - Thyrotropin-releasing hormone and cyclo (His-Pro)-like immunoreactivities in the cerebrospinal fluids of 'normal' infants and adults, and patients with various neuropsychiatric and neurologic disorders. AB - Levels of thyrotropin-releasing hormone (TRH) - and cyclo(His-Pro) (CHP)-like immunoreactivities and the activity of enzyme Pyroglutamate aminopeptidase (PAPase) were measured in cerebrospinal fluid (CSF) of over 100 normal adults (NA) and infants, and adult patients with various neurologic and neuropsychiatric disorders (NNDA). Levels of TRH and CHP in CSF of over 70% of the NA group were below 50 and 500 pg/ml respectively. The TRH- and CHP-like immunoreactivities in the remainder of the 30% of NA specimens exhibiting higher peptide concentrations were enzymatically and chromatographically characterized and were found to behave like authentic peptides. The levels of both of these peptides were significantly elevated in the CSF of most of the NNDA patients. An elevation in the CSF level of CHP was significantly correlated with the level of TRH, but not PAPase. Results from this study suggest that CSF elevation of TRH level may be due to a nonspecific response to stress that may be associated with hospitalization, myelogram procedure, and/or the neurologic and neuropsychiatric diseases for which the patients were admitted. PMID- 2891015 TI - Studies of high and low insulin responders with the hyperglycemic clamp technique. AB - We have investigated insulin responsiveness in relation to insulin sensitivity during sequential hyperglycemic clamping in low insulin responders (LIR), high insulin responders (HIR) and in women with a history of gestational diabetes (GD). Designation of HIR and LIR was done on the basis of mathematical modeling of the insulin response to a glucose infusion test. Insulin sensitivity was determined by a somatostatin-insulin-glucose infusion test (SIGIT) according to which LIR were subdivided into groups with higher or lesser sensitivity. Hyperglycemic clamping (60 min, 11 mmol/L of glucose) induced diphasic insulin and C-peptide responses in all groups. Insulin and C-peptide responses were significantly higher in HIR than in other groups. The ratio of first phase to total insulin response was higher in HIR v GD but did not differ between other groups. A second identical clamp was performed after a 60-minute rest period. Except in HIR, insulin levels attained were then moderately but significantly higher than during the first clamp. Conversely, the glucose utilization (mg/kg/min) to insulin (mU/L) = M/L ratio was markedly increased in LIR with high insulin sensitivity but not in other groups. We conclude that (1) large and consistent differences exist in glucose-induced insulin secretion from the pancreas between nondiabetic subjects; (2) time dynamics of insulin secretion and priming effects of glucose are similar in LIR with lesser and higher sensitivity; and (3) in the latter group a glucose stress affects insulin sensitivity more markedly than insulin responsiveness. PMID- 2891016 TI - Purification of type-beta transforming growth factor from human platelets. PMID- 2891017 TI - An assay for type-beta transforming growth factor receptor. PMID- 2891018 TI - Identification of receptors for type-beta transforming growth factor. PMID- 2891019 TI - A prostaglandin theory of neuroleptic malignant syndrome. AB - A subgroup of patients with schizophrenia or other psychoses may have an increased PGE receptor sensitivity in the brain, which may be due to low levels of PGE. Some of these patients may develop a severe dopaminergic blockade when given neuroleptics which stimulate PGE synthesis. This may lead to the symptoms of neuroleptic malignant syndrome. Calcium channel blockers inhibit the prostaglandin output caused by norepinephrine and these agents may prove useful in the treatment of neuroleptic malignant syndrome. PMID- 2891021 TI - Terazosin for hypertension. PMID- 2891020 TI - The treatment of tremor. PMID- 2891022 TI - [Terfenadine and automobile driving. A placebo controlled double-blind study of the effect of different antihistamines on driving behavior]. PMID- 2891023 TI - Disruption of neostriatal development in rats following perinatal exposure to mild, but chronic carbon monoxide. AB - The vulnerability of the developing neostriatum to mild, but chronic hypoxia was evaluated in weanling rats exposed only in utero or from conception through postnatal day 10 to 0, 75, 150, and 300 ppm carbon monoxide (CO). The exposure conditions produced maternal carboxyhemoglobin (HbCO) levels of about 11, 19, and 27 percent. HbCO levels of 5 percent are maintained by human cigarette smokers while comparable levels in non-smokers average less than 1%. Significant elevations in DNA and the neurotransmitter, dopamine (DA), were observed in the striatum of 21-day-old rats following the combined pre- and neonatal CO exposure. These neurochemical changes were observed 11 days after CO exposure was terminated and, therefore, cannot be interpreted as acute responses to reduced oxygen. These data indicate that the immature neostriatum is altered by even mild hypoxic insults presented during the time of neuronal proliferation and synaptogenesis. PMID- 2891024 TI - Prenatal cocaine use associated with down regulation of receptors in human placenta. AB - Cocaine use during pregnancy has been associated with abruptio placentae and spontaneous abortions. These effects may be secondary to the vasoconstrictive effects of cocaine or to other alterations. Since it has been demonstrated that the use of opiates during pregnancy alters placental receptors, the effects of cocaine on placental receptors was studied. Women who used cocaine during pregnancy showed a significant lowering of the total number of beta-adrenergic receptor binding sites and delta-opiate receptor binding sites. The decreases in Bmax for each of these receptors was not associated with a decrease in the Kp. The potential causes for the receptor down regulation and effects are discussed. PMID- 2891025 TI - Adult T-cell leukemia/lymphoma associated with human T-lymphotropic virus type I (HTLV-I) infection--North Carolina. PMID- 2891026 TI - In vitro study of alpha 2-adrenoceptor turnover and metabolism using the adenocarcinoma cell line HT29. AB - We have utilized the adenocarcinoma cell line HT29 as an in vitro model to investigate the turnover and the metabolism of the alpha 2-adrenoceptor. The biosynthesis rate of the receptor was studied in postconfluent HT29 cells, when its density expressed as fmol/mg of cell membrane protein is constant, by following the recovery of the receptor binding capacity after blockade with the non-reversible alpha-adrenergic antagonist benextramine. Study of the inhibition of [3H]yohimbine and [3H]UK-14,304 binding showed that benextramine was a more potent antagonist at alpha 2-adrenoceptor than phenoxybenzamine. The incubation of intact HT29 cells for 30 min in the presence of 10(-5) M benextramine irreversibly blocked more than 95% of the alpha 2-adrenoceptors and totally suppressed the inhibitory effect of UK-14,304 on cyclic AMP production. The blockade appeared specific, since benextramine effects were prevented by alpha 2 adrenergic agents. Moreover, neither vasoactive intestinal polypeptide responsiveness nor other tested aspects of the regulation of the adenylate cyclase was altered by the treatment. Study of the time course of receptor recovery after irreversible blockade indicated that alpha 2-adrenoceptors reappeared in the cells with a monoexponential kinetic. The linearization of the repopulation curve obtained with the labeled antagonist [3H]yohimbine allowed the determination of the rate constant for receptor degradation (k = 0.0268 +/- 0.0025 hr-1) and the rate of receptor synthesis (6.91 +/- 0.64 fmol/mg of cell membrane protein/hr) corresponding to the synthesis of about 500 receptors/cell/hr. The alpha 2-adrenoceptor half-life was 26 +/- 3 hr. Measurement of the biological effects associated to the alpha-adrenoceptor stimulation during the course of receptor recovery indicated a relationship between the number of cell receptors and the percentage of inhibition of the cyclic AMP accumulation induced by forskolin. The receptor reappearance was totally inhibited by either actinomycin or cycloheximide or tunicamycin, showing that the recovery corresponded to de novo synthesized receptor and giving indirect evidence for the glycoproteic nature of the alpha 2-adrenoceptor. Deprivation for glucose or glutamine also impeded the recovery process; by contrast, addition of UK-14,304 or clonidine did not interfere, indicating that the expression of the alpha 2-adrenoceptor is not subject to homologous regulation in the HT29 cell. PMID- 2891027 TI - Relationship between alpha 2-adrenergic receptor binding sites and the functional receptors inhibiting norepinephrine release in rat cerebral cortex. AB - The properties of alpha 2-adrenergic receptor binding sites and the receptors inhibiting [3H]norepinephrine (3H-NE) release from slices of cerebral cortex were compared. [3H]RX 781094, an alpha 2-adrenergic receptor antagonist radioligand, labeled a single class of binding sites in membranes at 37 degrees with the pharmacological specificity expected of alpha 2-adrenergic receptors. 5' Guanylimidodiphosphate (Gpp(NH)p) and NaCl caused small increases in the potencies of antagonists at the 3H-RX binding sites but decreased the potencies of agonists 4-22-fold. Antagonists blocked the inhibition of potassium-evoked 3H NE release caused by exogenous NE with potencies similar to those in competing for 3H-RX binding sites. Partial receptor inactivation with N-ethoxycarbonyl-2 ethoxy-1,2-dihydroquinoline (EEDQ) was used to determine whether there was a receptor reserve. EEDQ dose-dependently decreased both the density of 3H-RX binding sites and the maximal inhibition of 3H-NE release by different agonists. For most agonists, KA values calculated after the receptor inactivation did not differ significantly from EC50 values; however, for epinephrine a small receptor reserve was apparent. The proportion of 3H-RX binding sites lost was similar to the proportion of functional receptors lost after EEDQ treatment. The functional KA values for agonists correlated most closely with KD values for the low affinity binding state observed in the presence of Gpp(NH)p and NaCl. However, both epinephrine and NE still showed two-site binding curves under these conditions, and it was the high affinity subpopulation of sites observed in the presence of Gpp(NH)p and NaCl which resembled most closely the functional KA values. These data suggest that 3H-RX labels binding sites with properties similar to the alpha 2-adrenergic receptors inhibiting 3H-NE release in cerebral cortex. There is little or no receptor reserve for this effect, and there appears to be a binding state for the natural catecholamine agonists which has an affinity lower than that for mediating this functional response. PMID- 2891028 TI - Domains of beta-tubulin essential for conserved functions in vivo. AB - The relationship between the primary sequence of tubulins and their properties in cells was studied by gene transfection experiments. Previously, we studied a chimeric beta-tubulin formed from chicken beta-tubulin-2 sequences in the amino terminal portion and the highly divergent Saccharomyces cerevisiae TUB2 sequences in the carboxy-terminal 25% of the molecule. In the cytoplasm of cultured animal cells, this protein incorporates into all microtubule structures and assembles with the same efficiency as endogenous tubulin. We show that the protein products of chimeric genes with an increasing proportion of yeast sequence, extending 5' of the carboxy-terminal 25%, are abnormal in two ways. First, they assemble with a significantly lower efficiency than the original chimeric protein or the endogenous tubulins. Second, they are less stable in the cytoplasm. The results suggest that the position of the yeast sequences is crucial in determining the properties of the molecule. Results of analyses of 1 deletion mutation and 10 linker insertions in the original chimeric tubulin suggest that those changes made outside the carboxyl terminus completely disrupt assembly activity, while those made in the carboxyl terminus do not. PMID- 2891030 TI - Serotonergic mechanisms of hallucinogenic drug effects. PMID- 2891029 TI - Murine Hox-1.7 homeo-box gene: cloning, chromosomal location, and expression. AB - A new murine homeo-box, called Hox-1.7, has been identified in a rare cDNA from F9 teratocarcinoma stem cells. The Hox-1.7 homeo-box is 68 and 72% homologous to the Drosophila antennapedia (Antp) and iab-7 homeo-boxes, respectively. A major 2.5-kilobase transcript and several minor transcripts were detected by Northern blot (RNA blot) analysis in adult tissues as well as in midgestational embryos. The posterior spinal cord was found to be a major site of Hox-1.7 expression in 12.5-day-old embryos. Somatic cell hybrids were used to map the Hox-1.7 gene to mouse chromosome 6. Restriction fragment length polymorphisms associated with either the Hox-1.7 gene or the previously known Hox-1 complex were identified. Their distribution patterns in recombinant inbred mouse strains were used to determine the linkage between the two loci as well as to other loci on chromosome 6. This maps Hox-1 and Hox-1.7 close to two mouse loci that affect morphogenesis, postaxial hemimelia (px) and hypodactyly (Hd). PMID- 2891031 TI - Massive intraabdominal bleeding in polyarteritis nodosa. PMID- 2891032 TI - Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. The role of gastric colonization. AB - Gram-negative nosocomial pneumonia may result from retrograde colonization of the pharynx from the stomach, and this may be more likely when the gastric pH is relatively high. We studied the rate of nosocomial pneumonia among 130 patients given mechanical ventilation in an intensive care unit who were receiving as prophylaxis for stress ulcer either sucralfate (n = 61), which does not raise gastric pH, or conventional treatment with antacids, histamine type 2 (H2) blockers, or both (n = 69). At the time of randomization to treatment, the two groups were similar in age, underlying diseases, and severity of acute illness. Patients in the sucralfate group had a higher proportion of gastric aspirates with a pH less than or equal to 4 (P less than 0.001) and significantly lower concentrations of gram-negative bacilli (P less than 0.05) in gastric aspirates, pharyngeal swabs, and tracheal aspirates than did patients in the antacid-H2 blocker group. The rate of pneumonia was twice as high in the antacid-H2 group as in the sucralfate group (95 percent confidence interval, 0.89 to 4.58; P = 0.11). Gram-negative bacilli were isolated more frequently from the tracheal aspirates of patients with pneumonia who were receiving antacids or H2 blockers. Mortality rates were 1.6 times higher in the antacid-H2 group than in the sucralfate group (95 percent confidence interval, 0.99 to 2.50; P = 0.07). Although our results fell just short of statistical significance when they were analyzed according to intention to treat, they suggest that agents that elevate gastric pH increase the risk of nosocomial pneumonia in patients receiving ventilation by favoring gastric colonization with gram-negative bacilli. We conclude that in patients receiving mechanical ventilation, the use of a prophylactic agent against stress ulcer bleeding that preserves the natural gastric acid barrier against bacterial overgrowth may be preferable to antacids and H2 blockers. PMID- 2891034 TI - Incidence of recreational use of 3,4-methylenedimethoxymethamphetamine (MDMA, "ecstasy") on an undergraduate campus. PMID- 2891033 TI - Expression of opioid peptides in tumors. AB - We looked for opioid peptides and their precursors in 108 tumors of both neuroendocrine and nonneuroendocrine origin, using a monoclonal "pan-opioid" antibody, 3-E7, which recognizes the tetrapeptide Tyr-Gly-Gly-Phe (the sequence responsible for pharmacologic activity in all known opioid peptides), in conjunction with polyclonal antibodies directed against representative peptides of each of the three precursors (alpha-endorphin, [met]enkephalin-Arg-Gly-Leu, and dynorphin B). Using the avidin-biotin immunoperoxidase technique, we observed consistent cytoplasmic immunoreactivity (at least focally) in all of 15 adrenal pheochromocytomas, all of 6 thyroid medullary carcinomas, and all of 5 pituitary adenomas. Opioid staining was also observed in parathyroid adenomas (8 of 9), pancreatic islet-cell tumors (7 of 10), carcinoid tumors from various sites (18 of 26), and paragangliomas (1 of 2). There was no immunoreactivity in pulmonary small-cell carcinomas, Merkel-cell tumors of skin, neuroblastomas, or any of the non-neuroendocrine tumors examined. The expression of alpha-endorphin, [met]enkephalin-Arg-Gly-Leu, and dynorphin B varied from tumor to tumor; however, positive staining with the "pan-opioid" antibody was found in each tumor containing at least one of the three precursors. Opioid peptide immunoreactivity was also detected in non-neoplastic cells of the adrenal medulla, pancreatic islets, pituitary, intestinal and bronchial mucosa, and intestinal myenteric plexuses. We conclude that opioid expression within tumors is most likely due to enhanced expression of a normal cell product and that opioid peptides are useful markers of neuroendocrine differentiation in many tumors. PMID- 2891035 TI - The burden of proof in linking AIDS to scrapie. PMID- 2891036 TI - Maternal regulation of zerknullt: a homoeobox gene controlling differentiation of dorsal tissues in Drosophila. AB - The homoeobox gene zerknullt (zen) plays an important role in the differentiation of dorsal tissues during Drosophila development. zen- embryos show transformations in the dorsal-most regions of the fate map, and lack several tissues that normally derive from these regions, including the amnioserosa and optic lobe. zen displays a simple dorsal on/ventral off pattern as early as cleavage cycle 10-11 (ref. 2). We have prepared a polyclonal antibody against a full-length zen protein, and used this to examine its pattern of expression in mutants that disrupt dorsal-ventral polarity. Most or all of the maternally expressed genes that are involved in this process have been previously identified and fall into two classes, so called 'dorsalizers' and 'ventralizers' (see refs 4 7, reviewed in ref. 8). On the basis of our analysis of zen expression in each of these maternal mutants we propose that one or more of the dorsalizing genes encodes a repressor which inhibits the expression of zen in ventral regions of developing embryos. The ventralizing gene cactus might play an important role in restricting the activity of this repressor to ventral regions, thereby permitting the activation of zen in those dorsal tissues where its function is critically required. PMID- 2891037 TI - Cholinergic modulation of the release of 5-hydroxytryptamine from the guinea pig ileum. AB - Isolated segments of the guinea pig ileum were vascularly perfused and the release of 5-HT and its metabolite 5-HIAA into the portal venous effluent determined by HPLC with electrochemical detection. Test substances were applied via the arterial perfusion medium. Oxotremorine inhibited concentration dependently the release of 5-HT and 5-HIAA (by 47% at 1 mumol/l). Scopolamine (0.1 mumol/l) did not affect the release of 5-HT and 5-HIAA, but antagonized the effect of oxotremorine. In the presence of TTX (1 mumol/l), oxotremorine (1 mumol/l) increased the release of 5-HT by 150% and that of 5-HIAA by 220%. This increase was completely blocked by scopolamine. Hexamethonium (100 mumol/l) and TTX (1 mumol/l) reduced the release of 5-HT by 32 and 40%, respectively. DMPP (10 mumol/l) increased the release of 5-HT by 57%, and this effect was prevented by hexamethonium. Neither DMPP nor hexamethonium significantly affected the release of 5-HIAA. The enhancing effect of DMPP on 5-HT release was increased and prolonged in the presence of TTX or scopolamine. Nicotine (1, 10 or 30 mumol/l) alone did not cause a consistent increase in the release of 5-HT. However, in the presence of scopolamine nicotine increased the release of 5-HT by 57%. In conclusion, the release of intestinal 5-HT is facilitated via muscarine and nicotine receptors located on the enterochromaffin cells. Indirect evidence suggests that the release of 5-HT is additionally modulated by an as yet unknown inhibitory neurotransmitter released by muscarine receptor activation. PMID- 2891038 TI - The role of alpha 1- and alpha 2-adrenoceptors in the coronary vasoconstrictor responses to neuronally released and exogenous noradrenaline in the dog. AB - 1. Coronary vasoconstriction was examined in response to the neuronal release of noradrenaline produced by bilateral carotid occlusion and the infusion of tyramine (5-50 micrograms/kg/min i.v.) in anaesthetized dogs which had been vagotomized and treated with the beta-adrenoceptor antagonist propranolol (1.0 mg/kg i.v.). These responses were compared to those produced by the infusion of noradrenaline (0.1-0.5 micrograms/kg/min i.v.). 2. Similar increases in late diastolic coronary resistance were produced by bilateral carotid occlusion (0.70 +/- 0.25 mm Hg min/ml), and intravenous infusions of tyramine, 20 micrograms/kg/min (0.70 +/- 0.12 mm Hg min/ml) and noradrenaline, 0.5 micrograms/kg/min (0.59 +/- 0.11 mm Hg min/ml). 3. Selective antagonism at alpha 1-adrenoceptors with prazosin (0.5 mg/kg i.v.) attenuated the coronary constrictor response to bilateral carotid occlusion (0.36 +/- 0.09 mm Hg min/ml), tyramine (0.12 +/- 0.06 mm Hg min/ml) and noradrenaline (0.18 +/- 0.07 mm Hg min/ml). Antagonism at alpha 2-adrenoceptors with idazoxan (1 mg/kg i.v.) attenuated the coronary vasoconstriction produced by bilateral carotid occlusion (0.30 +/- 0.06 mm Hg min/ml), tyramine (0.17 +/- 0.08 mm Hg min/ml) and noradrenaline (0.12 +/- 0.03 mm Hg min/ml). Combined antagonism at both alpha 1- and alpha 2-adrenoceptors with prazosin and idazoxan abolished the responses to bilateral carotid occlusion, tyramine and noradrenaline. 4. These results show that coronary vasoconstriction produced by either neuronally released or exogenous noradrenaline is mediated by both alpha 1- and alpha 2-adrenoceptors. It appears that in the coronary resistance vessels of the dog postjunctional alpha 1- and alpha 2-adrenoceptors are both innervated by sympathetic nerves. PMID- 2891039 TI - Pharmacological profile of a new potent and specific alpha 2-adrenoceptor antagonist, L-657,743. AB - L-657,743,(2S,12bS)1',3'-dimethylspiro(1,3,4,5',6,6',7,12 b-octahydro-2H- benzo[b]furo[2,3-a]quinolizine)-2,4'-pyrimidin-2'-one, was tested in several in vitro and in vivo models for alpha 2-adrenoceptor antagonism. L-657,743 exhibited a high affinity (less than or equal to 1 nM) for alpha 2-adrenoceptors labelled by [3H] rauwolscine or [3H]clonidine with a 240-fold selectivity versus alpha 1 adrenoceptors labelled by [3H]prazosin. L-657,743 was a potent, selective, and competitive alpha 2-adrenoceptor antagonist in the rat isolated vas deferens (pA2 = 9.3 vs. clonidine; pA2 = 7.1 vs methoxamine). In vivo, L-657,743 potently blocked clonidine-induced mydriasis in the rat and stimulated cerebrocortical norepinephrine synthesis, two indices of central alpha 2-adrenoceptor antagonism. L-657,743 exhibited a comparatively low affinity for several monoamine receptor subtypes (D1, D2, 5-HT1, 5-HT2) in radioligand binding assays in vitro and a comparatively low potency to alter the synthesis of brain DA and 5-HT in vivo indicating a marked alpha 2-specificity versus other monoamine receptor mechanisms. Compared to yohimbine, L-657,743 had considerably higher alpha 2 antagonist potency and alpha 2/alpha 1 selectivity and was significantly more alpha 2-specific (i.e., vs. DA, 5-HT receptors). PMID- 2891040 TI - Trifluoperazine-sensitive activation of the spontaneous transmitter release at the frog motor endplates by low doses of procaine. AB - Low concentrations of procaine (10(-6)-5 X 10(-5) mol/l) induced a significant increase of the spontaneous quantal transmitter release in the neuromuscular junctions of the frog cutaneous pectoris nerve-muscle preparation. The frequency of miniature endplate potentials (mepps) was increased although their size slightly decreased probably on the account of a partial block of Na+-channels at the postsynaptic membrane. The activatory effect of pre-caine was not altered under experimental conditions known to change the Ca2+ fluxes across the nerve terminal membrane such as using a Ca2+-free Ringer, or a Ca2+-channel blocker (D600), a high K+ Ringer or, finally, a low Na+ Ringer. In the presence of caffeine no change of procaine-induced activation appeared. Trifluoperazine (TFP), in a concentration known to specifically block calmodulin, completely blocked the procaine-induced increase of mepp frequency. These data suggest that procaine presumably by way of a calmodulin-dependent mechanism is related to the free cytosolic Ca2+ equilibrium. It is possible that procaine increases the free cytosolic Ca2+ concentration by blocking an active calmodulin-dependent Ca2+ extrusion mechanism. PMID- 2891041 TI - Identification of the neuroeffector transmitter in jejunal branches of the rabbit mesenteric artery. AB - Vasoconstriction or excitatory junction potentials (e.j.ps) evoked by nerve stimulation (15 field pulses at 2 Hz every 3 min) were recorded in rabbit isolated jejunal arteries. The resting diameter of the arteries and its decrease in response to stimulation was measured by a photoelectric method. Vasoconstriction was insensitive to prazosin 0.1 or 1 mumol/l. Yohimbine 1 mumol/l considerably enhanced, whereas alpha,beta-methylene ATP (alpha,beta meATP) 1 mumol/l abolished the contractile response. In order to test the effect of exogenously applied transmitter candidates, noradrenaline (0.1-1 mumol/l) and ATP (10-30 mumol/l) were added in concentrations which evoked a vasoconstriction comparable to that induced by electrical stimulation. The action of noradrenaline was prevented by prazosin 0.1 mumol/l, but was unaffected by both yohimbine 1 mumol/l and alpha,beta-meATP 1 mumol/l. Alpha,beta-meATP 1 mumol/l depressed the effect of ATP. The e.j.ps evoked by a train of 15 pulses showed facilitation up to the third response and thereafter depression; a partial summation was also observed. Prazosin 0.1 mumol/l did not change the e.j.p. amplitudes. By contrast, when yohimbine 0.1 or 1 mumol/l was added to the prazosin-containing medium, both the late e.j.ps in the train and the summation were enhanced in a concentration dependent manner. Alpha,beta-meATP 1 mumol/l almost abolished the e.j.ps. In conclusion, in rabbit jejunal arteries, stimulation of postganglionic sympathetic nerves may release noradrenaline together with ATP which is probably the sole neuroeffector transmitter under our conditions. Transmitter release seems to be modulated by the activation of presynaptic alpha 2-adrenoceptors. Under the stimulation conditions of the present experiments the released transmitter does not activate postsynaptic alpha 1-adrenoceptors. PMID- 2891042 TI - Pertussis toxin does not attenuate alpha 2-adrenoceptor mediated inhibition of noradrenaline release in mouse atria. AB - 1. The alpha 2-adrenoceptor agonist clonidine (0.03 and 0.1 mumol/l) significantly inhibited stimulation-induced overflow of radioactivity from mouse isolated atria preincubated with [3H]-noradrenaline. This effect of clonidine was blocked by idazoxan (0.3 mumol/l) but not prazosin (0.3 mumol/l), indicating that an alpha 2-adrenoceptor was involved. 2. In some experiments mice were injected with pertussis toxin (1.5 micrograms/mouse) 4 days before their atria were removed and subsequently incubated with [3H]-noradrenaline. Alternatively, isolated atria from untreated mice were suspended in Krebs-Henseleit solution, incubated for 16 h with pertussis toxin (1.0 and 4.0 micrograms/ml) or vehicle and subsequently incubated with [3H]-noradrenaline. The effectiveness of pertussis toxin pretreatment was assessed indirectly using carbachol. Carbachol caused a dose dependent fall in both the rate and force of contraction of isolated, spontaneously beating atria from mice pretreated with vehicle in vivo or in vitro. This effect of carbachol was not seen in atria from mice pretreated with pertussis toxin in vivo or in vitro, suggesting that active toxin penetrated the myocardium. 3. Pertussis toxin pretreatment, either in vivo or in vitro did not alter the inhibitory effect of clonidine (0.03 and 0.1 mumol/l), or the facilitatory effect of the alpha-adrenoceptor antagonist phentolamine (1.0 mumol/l), on the stimulation-induced overflow of radioactivity. These results suggest that alpha 2-adrenoceptor modulation of noradrenaline release from sympathetic nerve terminals is not dependent on an inhibitory guanine-nucleotide binding protein. PMID- 2891043 TI - Effect of endothelium and carbachol on alpha-adrenoceptor agonist stimulated uptake and efflux of 45Ca in rat isolated aorta. AB - Preincubation with carbachol (10 microM) did not affect basal 45Ca accumulation by rat isolated aortic segments complete with endothelium, although 45Ca accumulation was enhanced by removal of endothelium. This confirms the observation that in the presence of endothelium Ca2+ influx in rat aorta is antagonized, and indicates that the basal release of an endothelial derived factor might be sufficient to maximally antagonize basal Ca2+ influx, or alternatively that EDRF released as a result of muscarinic stimulation does not have identical effects to the factor released under basal conditions. Accumulation of 45Ca stimulated by B-HT 920 but not that stimulated by phenylephrine was antagonized in the presence of endothelium. Contractions elicited by B-HT 920 were abolished in the presence of endothelium while contractions evoked by phenylephrine were reduced by about 50%. Preincubation with 10 microM carbachol antagonized both phenylephrine (1 microM) stimulated 45Ca accumulation and contractile responses in the presence of endothelium to about the same extent. Therefore, it might be concluded that the inhibitory effect of EDRF in this tissue is due to an inhibition of stimulated Ca2+ influx. However, while addition of carbachol to tissues precontracted with phenylephrine elicited an immediate relaxation in the presence of endothelium, this relaxation could not be correlated with a reduction in tissue accumulation of 45Ca. Carbachol also antagonized the phenylephrine-induced reduction of tissue 45Ca content (i.e. efflux of Ca2+), in tissues preloaded with 45Ca. This implies that the initial endothelial-mediated relaxant effect of carbachol in precontracted tissues cannot be explained either by reduced influx or by an enhanced efflux of Ca2+ from the smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891045 TI - Analysis of the nature of antagonism of the reserpine-induced hypothermia by imipramine. AB - Antagonism of reserpine-induced hypothermia is an animal model used in the screening of antidepressants. The activity of imipramine on this test is partly impaired by propranolol. This effect of imipramine was analyzed using specific adrenoceptor and 5-HT receptor blocking drugs in order to determine the nature of this effect of propranolol. The non-selective beta 1-beta 2 adrenoceptor antagonist, propranolol as the specific beta 1 adrenoceptor antagonist betaxolol, but not the specific beta 2 blocking drug DL-erythro-3-isopropylamino-1-(7-methyl 4-indanyloxy)-2-butanol hydrochloride 313.9 (ICI 118,551), partly antagonized the effect of imipramine at 30 min. None of the serotonin (5-HT) receptor antagonists, methysergide, metergoline, ritanserin and buspirone, impaired the effect of imipramine. On the contrary, methysergide alone antagonized reserpine induced hypothermia and methysergide or metergoline increased the action of imipramine. Propranolol impaired neither the hypothermia induced by an agonist at the 5-HT 1A receptors: 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) nor the increase in spontaneous motor activity induced by an agonist at the 5-HT 1B receptors: 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1-H indole (Ru 24,969). It is concluded that the effect of propranolol is not the result of a blockade of 5 HT 1A, 5-HT 1B or 5-HT 2, but is in part due to blockade of beta 1 adrenoceptors. PMID- 2891044 TI - Further studies on (+/-)-YM-12617, a potent and selective alpha 1-adrenoceptor antagonist and its individual optical enantiomers. AB - YM-12617, 5-[2-[[2-(o-ethoxyphenoxy)ethyl]amino]propyl]- 2 methoxybenzenesulfonamide HCl is structurally novel, an extremely potent and highly selective alpha 1-adrenoceptor antagonist. An asymmetric center exists at the alpha-carbon atom in the phenethylamine portion of YM-12617, therefore two optical enantiomers exist. alpha-Adrenoceptor blocking properties and hypotensive activities of YM-12617 and its enantiomers have been compared in vitro and in vivo. 1. In the isolated rabbit aorta, R(-)- and S(+)-YM-12617 competitively antagonized phenylephrine-induced contraction with pA2 values of 9.95 and 7.69, respectively. Although R(-)- and S(+)-YM-12617 were also competitive antagonists toward UK-14,304 at prejunctional alpha 2-adrenoceptors in the isolated guinea pig ileum, the affinities of R(-)-YM-12617 (pA2 = 6.18) and S(+)-YM-12617 (pA2 = 5.64) for these receptors were 5,900 and 110 times lower than those displayed for postjunctional alpha 1-adrenoceptors in the isolated rabbit aorta. 2. R(-)- and S(+)-YM-12617 displaced both 3H-prazosin and 3H-idazoxan binding to rat brain membranes; however, the affinities of the R(-)- and S(+)-enantiomers for alpha 1 adrenoceptors (pKi = 9.95 and 7.83, respectively) were 21,000 and 72 times higher than those for alpha 2-adrenoceptors (pKi = 5.62 and 5.97), respectively. 3. Based on pA2 values obtained in the isolated tissues and pKi values in the binding assays, R(-)-YM-12617 was 132-182 times more potent than S(+)-YM-12617 as an antagonist at alpha 1-adrenoceptors. In contrast, the R(-)- and S(+) enantiomers were similar in potency at blocking alpha 2-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891046 TI - Kinetic analysis of the interaction of mifentidine with gastric H2-receptors in the conscious dog. AB - The H2-receptor antagonists mifentidine and cimetidine were compared for their ability to antagonize the activation of H2-receptors in the conscious dog. Dose response curves to dimaprit in stimulating gastric secretion were displaced to the right in a dose-related fashion by both drugs. Schild and Eadie-Hofstee analysis of these data indicated that mifentidine and cimetidine inhibited in vivo activation of H2-receptors in a manner compatible with competitive surmountable antagonism. Mifentidine displayed a 24fold greater potency than cimetidine as H2 antagonist in the conscious dog. PMID- 2891047 TI - [Treatment of asthma in childhood]. PMID- 2891048 TI - [Early diagnosis in sex-linked agammaglobulinemia]. PMID- 2891049 TI - [Drugs in angina pectoris]. PMID- 2891050 TI - [Consensus management policy for the undescended testis]. PMID- 2891051 TI - [Treatment of local infections, cranial and spinal, with suction irrigation drainage. Experiences in 60 patients]. AB - In 60 cases with postoperative infection we used local suction/irrigation drainage with primary wound closure. This method has some advantages 1. Healing needs much less time, especially in spinal localisations and 2. in one third of cranial infections removal of the bone flap was not necessary. PMID- 2891052 TI - [Local treatment of infections in neurosurgery with gentamicin PMMA chains (Septopal)]. AB - Treatment of infections after neurosurgical operations at the head and vertebral column is lengthy and stressful for the patient. Hence, we implanted--as has been routine in septic bone surgery for a long time--carriers of antibiotics for local antibiotic therapy in the form of Septopal chains. The course of treatment and the results obtained in 16 patients are presented. In all patients the wound cavities were filled with Septopal chains after debridement. In the course of 6 12 days the chains projecting from the skin by a stab incision were extracted sphere by sphere. The treated wound healed immediately in 14 patients; healing was delayed in 2 patients, but there were no complications. Since the use of Septopal chains results in local gentamicin levels which are so high that the conventional classification of germs into gentamicin-sensitive/gentamicin resistant is of minor importance, the wounds healed without complications even in those patients where the germs had been classified as "resistant" in the routine antibiogram. Thus, Septopal offers the advantage of primary wound closure without secondary contamination or scatter into the environment (intensive-care ward!), shorter treatment time, reduced stress for the patient and more rapid mobilisation. PMID- 2891053 TI - Acute subdural and subgaleal empyema. AB - A case is presented in which the initial CT scan failed to demonstrate subdural suppuration over both convexities. Definitive CT finding of subdural empyema (SDE) was only positive at an advanced stage, when a bilateral subgaleal empyema also spread out. Because of the fulminant development of the subdural empyema and the delayed diagnosis, the outcome was fatal in spite of neurosurgical operation. Subdural empyema is a neurological and neurosurgical emergency. Early diagnosis is imperative, because the mortality is about 25-40% and the outcome depends upon the promptness of diagnosis and the appropriate operation. In the recent literature the value of computerised tomography for early detection of subdural empyema is controversial. Some reports failed to demonstrate any evidence of purulent subdural collection in CT scans while others were able to make an early diagnosis. This report presents a case which demonstrates the difficulties in making an early diagnosis of a subdural empyema by CT. PMID- 2891054 TI - Monotherapy or polytherapy in migraine. AB - The majority of current therapeutic papers concerns the prophylactic therapy of migraine using only one drug, very few advocating the simultaneous use of two drugs. The theoretical usefulness of polytherapy in migraine is examined with examples from personal experience, and found justified. PMID- 2891055 TI - Genotypic differences in central neurotransmitter responses to aging in mice. AB - Dopamine, serotonin, cholinergic and somatostatin responses to aging have been followed in striatum and hippocampus of two inbred strains of mice (C57BL and BALB/c). A striking strain dependency is noted. Dopaminergic mechanisms in BALB/c mice become particularly defective in striatum where both dopamine release and dopamine turnover are affected. Also, striatal cholinergic activity and somatostatin levels are more disturbed in BALB/c than in C57BL mice. For cholinergic neurotransmission and somatostatin levels, similar results are noted in hippocampus. Conversely, C57BL mice react to aging by increased serotonin turnover in hippocampus and decreased 5HIAA levels in both structures studied, whereas the BALB/c strain remains unaffected. Also, structure dependency is observed: in C57BL mice serotonin turnover appears to be unchanged in striatum and increased in hippocampus; in the BALB/c the slowing down of dopamine activity in striatum is not observed in hippocampus. This unequal capacity of central neurotransmitters and neuromodulators to adapt to aging processes, depending upon the genotype, the nervous structure and the neurotransmitter considered may be involved in man in specific pathologies in aged individuals. PMID- 2891056 TI - Age-induced differentiation of morphine's effect on cyclic nucleotide metabolism. AB - Male ICR mice, immature (25 days old), mature adult (3 months old) and aged (22 months old), were injected with morphine sulfate (10 mg/kg, SC) or were implanted with morphine pellets (75 mg). Age-matched controls received saline injections or placebo pellets. One hour after injections and 72 hours after pellet implantation (when tolerance to morphine had occurred), the mice were decapitated and the frontal cortex and cerebellum were removed. Basal activities of adenylate cyclase, guanylate cyclase, cyclic AMP phosphodiesterase and cyclic GMP phosphodiesterase were determined in both brain regions. Results showed that there are age- and region-differentiated effects of morphine on these enzymes. PMID- 2891058 TI - A fraction enriched in dendrodendritic synaptosomes isolated from rat olfactory bulb: morphology and transmitter release. AB - A fraction enriched in dendro-dendritic synaptosomes was isolated from rat olfactory bulb by a rapid method. Synaptosomes preserved their ultrastructure and showed configurational changes in relation to incubation in physiological ion medium as described earlier in the case of cortical synaptosomes. Dendro dendritic synaptosomes were larger and contained more mitochondria than cortical synaptosomes. Doublets of terminals synapsing with each other were frequently seen and each terminal contained synaptic vesicles. Oxygen consumption of dendro dendritic synaptosomes was decreased by ouabain and increased by 2,4 dinitrophenol. High-potassium medium evoked a considerable release of GABA and dopamine but not of noradrenaline or serotonin in accordance with histochemical published data. PMID- 2891057 TI - Similarities of adenosine uptake systems in astrocytes and neurons in primary cultures. AB - Uptake of extracellular adenosine was studied in primary cultures of astrocytes or neurons. Both cell types showed a high affinity uptake. The Km values were not significantly different (6.5 +/- 3.75 microM in astrocytes and 6.1 +/- 1.86 microM in neurons), but the intensity of the uptake was higher in astrocytes than in neurons (Vmax values of 0.16 +/- 0.030 and 0.105 +/- 0.010 nmol x min-1 x mg-1 protein, respectively). The temperature sensitivity was similar in the two cell types. Adenosine uptake inhibitors and benzodiazepines inhibited the adenosine uptake systems in both astrocytes and neurons with IC50 values in the high nanomolar or the micromolar range and the rank order of potency was similar in the two cell types. In both cell types the (-) isomers of two sets of benzodiazepine stereoisomers were more potent than the (+) isomers. Dixon analysis showed that dipyridamole, papaverine, hexobendine and chlordiazepoxide inhibited the adenosine uptake competitively and clonazepam noncompetitively in both cell types. PMID- 2891061 TI - The clinical significance of the P15 wave of the somatosensory evoked potential in tentorial herniation. AB - Somatosensory evoked potentials (SEPs) to median nerve stimulation and auditory brainstem evoked potentials (BAEPs) were recorded in 16 comatose patients who had suffered transtentorial herniation (TH) due to intracranial haematoma, hydrocephalus or tumour. An attempt was made to correlate the changes in the N14 P15 component of the central conduction time (CCT) and the I-V interpeak latencies (IPLs) of the BAEP with the clinical severity of TH. The N14-P15 component was not affected in seven patients at the diencephalic or early third nerve stage, and six of these seven showed normal I-V IPLs. All six patients at the late third-nerve/midbrain stage or worse, however, showed abnormalities in the N14-P15 components. Interestingly, five patients showed dissociation of SEP and BAEP abnormalities suggesting a differential sensitivity of the medial and lateral lemnisci in the brainstem to ischaemia and/or compression. All five patients in whom the P15 potential was absent on either side had a poor outcome and there was a correlation between the electrical failure in the N14-P15 component and the degree of brainstem damage caused by TH as assessed clinically. Reversible loss of the P15 potential by brainstem retraction has been shown in intraoperative SEP monitoring during aneurysm surgery. Prolonged compression of the upper brainstem seems to cause irreversible loss of the P15 which should be regarded as being due to irrecoverable brainstem dysfunction. PMID- 2891060 TI - Chick brain glutamine synthetase and Mn2+-Mg2+ interactions. AB - Glutamine synthetase (GS) from the chick brain was purified to apparent homogeneity by ammonium sulfate fractionation followed by affinity chromatography, electrofocusing and Sephadex G-150 chromatography. The purified enzyme showed a single band on sodium dodecyl sulfate analysis in polyacrylamide gel. By sedimentation equilibrium analysis and gel electrophoresis analysis, it was shown that the enzyme has a subunit molecular weight of 45,000 and a native molecular weight of 364,000, which is consistent with an octameric structure. Sedimentation analysis in the presence of Mg2+ revealed three different forms of macromolecules corresponding respectively to a monomer, a tetramer and an octamer. Among eight cations tested (Ca2+, Co2+, Fe2+, Li+, Mg2+, Mn2+, Ni2+, Zn2+) only Co2+, Mg2+ and Mn2+ supported GS activity; the order of activatory ability was Mg2+ greater than Co2+ greater than Mn2+. The maximum activating effect of Mn2+ occurs only within a very narrow range of concentration: with an excess of cation causing strong inhibition of GS activity. For each cation, maximal GS activity occurs at a defined cation/ATP ratio. A regulatory system in which Mn2+, modulates the Mg2+ dependent GS activity, is proposed; such cation interactions may be of significance in the intracellular control of glutamine synthesis. PMID- 2891059 TI - Differential alteration of dopamine, acetylcholine, and glutamate release during anoxia and/or 3,4-diaminopyridine treatment. AB - The potassium-stimulated release of acetylcholine (ACh), glutamate (GLU) and dopamine (DA) from mouse striatal slices was studied during anoxia and/or 3,4 diaminopyridine (DAP) treatment. Anoxia, in the presence of calcium, increased DA and GLU release, but depressed ACh release. Omission of calcium from an anoxic incubation further stimulated GLU and DA release and impaired ACh release. Under normoxic conditions, DAP (100 microM) increased the release of all three neurotransmitters; the sensitivity of the slices to DAP changed with the presence or absence of an acetylcholinesterase inhibitor in the preincubation media. During an anoxic incubation, DAP did not ameliorate the anoxic-induced, K+ stimulated impairment of ACh release, but significantly reduced the K+-stimulated release of GLU and DA. These results are consistent with the hypothesis that hypoxia induces a presynaptic deficit that may underlie postsynaptic ischemic induced changes. Amelioration of these presynaptic alterations in neurotransmitter release may be an effective approach to preventing hypoxic induced damage. PMID- 2891062 TI - Measurement of somatosensory evoked potential in the Mongolian gerbil: the effects of cerebral ischaemia. AB - Normal somatosensory evoked potential (SEP) as well as changes after incomplete cerebral ischaemia following bilateral carotid artery occlusion (BCO) were characterized in the Mongolian gerbil. BCO significantly decreased cerebral blood flow (CBF). Reperfusion CBF at 10 min and 2, 3 and 4 h was significantly below preischaemic control values. BCO decreased SEP amplitude but had no effect on EP P3 central conduction time. BCO did significantly increase EP-P11 central conduction time. Reperfusion amplitudes at 10 min and 2, 3 and 4 h revealed a significant increase only at 4 h when compared to the ischaemic amplitude. EP-P11 central conduction time at 10 min reperfusion showed dramatic improvement compared to ischaemic values, although values at 2, 3 and 4 h reperfusion were not statistically different from ischaemic values. A separate group of animals prepared identically but without BCO showed no significant changes in either SEP or CBF over time. These studies establish the protocol necessary to measure SEP in the Mongolian gerbil. In the future SEP may be used as an integral tool in the study of the primary determinants of neurophysiological recovery following cerebral ischaemia. PMID- 2891063 TI - Inhibitory effect of pentobarbital on phospholipase C activity in ischaemic rat brain. AB - Ischaemic rat brains were examined for temporal changes in phospholipase C activity with phosphatidylinositol; the effects of pentobarbital on the activity also were investigated. Ischaemia was produced by decapitation. Pentobarbital (60 mg/kg) was administered i.p. for 15 min before decapitation. The removed heads were incubated at 37 degrees C for 1, 5, 15 or 30 min and then quickly frozen in liquid nitrogen. After isolation of subcellular fractions from the brains, phospholipase C activity was measured for cytosol and microsomes, using radioactive phosphatidylinositol as a substrate. The results demonstrated that brain phospholipase C predominantly localized in the cytosol was dependent on Ca2+ for full activity and had neutral pH optima. Although the enzyme activity did not increase during ischaemia, pentobarbital inhibited phospholipase C activity in the cytosol but not in the microsomes. These observations suggest that pentobarbital may exert a cerebral protective action due to, at least in part, the repression of phospholipase C followed by a reduction of phosphatidylinositol breakdown, preventing perturbation to the integrity of membranes, during ischaemia. PMID- 2891064 TI - Spontaneous progressive thrombosis and surgical resection of a giant aneurysm of the posterior cerebral artery in an 18-year-old. AB - The rare case is reported of an 18-year-old boy with giant fusiform aneurysm of the P1 and P2 segments of the posterior cerebral artery. The symptoms were two episodes of sudden headache with transient third-nerve palsy. The aneurysm developed into almost complete thrombosis over five months. The posterior cerebral artery distal to the aneurysm was also thrombosed and reirrigated by collateral channels without visual field deficit. The aneurysm was treated by resection. The development of this giant aneurysm, the progressive thrombosis and the clinical characteristics are discussed. PMID- 2891065 TI - Origin of short latency somatosensory evoked potential in cats: especially potentials derived from thalamus and cortex. AB - Short latency somatosensory evoked potential (SSEP) was recorded in cats to identify the potentials originating from the cortex and the thalamus, and the following results were obtained. When SSEP was elicited on the bregma by stimulation of the contralateral superficial radial nerve, P2, P4, P4.5, P5.5, P7, P8, N8.5, P11, P9.5, N11.5, N12.5 and N14 were recognized. Of these components N11.5, N12.5 and N14 consisted of large negative potential (LNP). When KCl was applied to the sensorimotor cortex to induce spreading depression, the positive component of the primary evoked potential was markedly decreased and the negative component disappeared. In SSEP, components preceding N8.5 were unchanged. N8.5-P11 and P11-N12.5, however, markedly diminished or disappeared. The latency of the first component of the field potential recorded in the VPL nucleus of the thalamus was about 5 ms. When a small amount of Nembutal was injected into VPL nucleus, components between P2 and P4.5 remained unchanged, but P5.5 disappeared. P7, P8 and N8.5 were preserved. The amplitude of N8.5-P11 was markedly decreased and LNP disappeared. From these results, among various components of SSEP, P5.5 should originate from the thalamus, and P7, P8 and N8.5 from the extralemniscal system. N8.5-P11 should mainly represent post-synaptic potential (PSP) in the deep somatic layer, and P11-N12.5 represent PSP in the apical dentrites of the sensorimotor cortex. N14 probably represents PSP via the diffuse projection system. Thus, LNP should consist of complex potentials of specific and non-specific sensory systems. PMID- 2891066 TI - Intracranial pressure behaviour and its relation to the outcome of surgical CSF shunting in normotensive hydrocephalus. AB - Twenty-four patients with suspected normotensive hydrocephalus were surgically treated by cerebrospinal fluid (CSF) ventriculoatrial or peritoneal shunt. The results of surgery were considered in relation to clinical history and different diagnostic examinations: pneumoencephalography, CT scan, isotope cisternography, transfer from CSF to blood of isotope-labelled serum albumin, constant infusion manometric test, intraventricular pressure recording. Intracranial pressure (ICP) was analysed during both resting conditions and spontaneously (REM phase of sleep) or artificially induced (jugular compression) increases. The ventricular enlargement (as shown by CT scan) and the slope of the intracranial elastance (the ratio of the differences between the maximum and minimum values of pulse ICP and the correspondent values of the diastolic ICP under the same dynamic conditions) provided the most reliable data for diagnosis and surgical prognosis. PMID- 2891067 TI - Constrictive structural elements in human cerebral arteries following aneurysmal subarachnoid haemorrhage. AB - Histoimmunological, histochemical, and histological studies were conducted on cerebral arteries from four living patients with a recent aneurysmal subarachnoid haemorrhage. There appeared to be a correlation between the severity of vasospasm and the magnitude of pathological findings. Large myofibroblast cells and type V collagen within the medial layer were abundant in arteries showing marked vasospasm, but were less conspicuous in those showing milder involvement. Intracranial arteries from patients who died from non-cerebral causes did not demonstrate these changes. In ruptured vessels, there was also a positive fluorescence for actin-myosin filaments in layers of the arterial wall other than the media. It is postulated that the intimal and adventitial actin-myosin, myofibroblasts and type V collagen may contribute to cerebral vasospasm by holding the damaged vessel in a contracted phase during the healing period. PMID- 2891068 TI - Supratentorial pressures. Part I: Differential intracranial pressures. AB - Dynamic supratentorial pressure changes may differentially alter tissue pressure and intraventricular fluid pressure. To evaluate these pressures, we used a floppy cuff intracerebral catheter and an intraventricular catheter in the cat and rhesus monkey. Baseline intraventricular pressures exceeded intracerebral pressure in both species. Intraventricular pressure was 3-4 mmHg in cats and 6-14 mmHg in monkeys, while the intracerebral pressure was in the range 0-4 mmHg in both. Saline injection into the spinal or cranial subarachnoid space resulted in a greater increase in ventricular fluid pressure, and the time for return to baseline was one and a half times longer in the intraventricular compartment. Jugular venous and abdominal compression resulted in a greater rise in the ventricular pressure than intracerebral pressure. Inflation of subdural balloons and intracerebral injection of silicone caused a differential pressure across the brain with the pressure being greatest in the ipsilateral hemisphere and lowest in the contralateral hemisphere. Rapidly evolving epidural masses produced varied results. We did not evaluate compensatory pressure changes in these animals. Those pressures that involve cerebrospinal fluid (CSF) dynamics alter intraventricular pressure more than tissue pressure. Alternatively, rapidly forming masses tend to increase tissue pressure near the mass more than intraventricular pressure. PMID- 2891070 TI - Exposure time and frequency of irradiation in brain tumours. AB - The survival of a group of patients with malignant gliomas of the brain submitted to radical surgery and radiotherapy was studied. The average survival was nearly 4 times longer with X-ray treatment than with cobalt 60 irradiation when a comparison was made between 24 patients with glioblasto-astroblastoma (grade 3-4) who received one or the other type of treatment (12 patients in each group). These results are ascribed to the fact that the daily exposures to X-ray were much longer than with cobalt and so, during those prolonged sessions, a greater number of tumour cells could be destroyed as they successively reached the pre mitotic period of enhanced vulnerability to radiation. A smaller group of patients irradiated with linear accelerators fared worse than those who received X-ray treatment. Changes to the parameters of irradiation used at the present time with cobalt units or linear accelerators are suggested. PMID- 2891069 TI - Supratentorial pressures. Part II: Intracerebral pulse waves. AB - Intracerebral pulse waves were recorded in cat and monkey while intracranial pressure (ICP) manipulations were performed. The intracerebral pulse waves appeared comparable to cerebrospinal fluid (CSF) pulsations. The wave forms were divided into multiple smaller waves, designated P1 to P4. The P1 component was primarily of arterial origin and was accentuated by increasing ICP unrelated to increased venous pressure, most commonly from a mass lesion. Bilateral carotid occlusion resulted in decreased amplitude of P1. Venous hypertension from jugular venous or sagittal sinus occlusion, on the other hand, accentuated waves P2 and P3 more than P1. This is consistent with a Starling resistor model of the cerebral venous system in which mass lesions may compress low-pressure veins and accentuate the arterial pressure-dependent P1 wave, whereas venous hypertension causes increased prominence of the later P2 and P3 waves. PMID- 2891071 TI - Somatostatin-like immunoreactivity in cerebroventricular fluid of patients with basal midline tumours. AB - The concentration of somatostatin-like immunoreactivity (SLI) was determined by specific radioimmunoassay in the cerebroventricular fluid of patients with tumours of the basal midline and compared to findings in patients with multiple sclerosis. Mean SLI levels of the two groups were not significantly different. In patients with basal tumours (astrocytoma, craniopharyngioma, etc.) SLI levels varied widely and tended to increase with increased intracranial pressure. Lateral ventricular SLI levels decreased in patients with blockade of foramen Monro and in patients with communicating hydrocephalus or post-radiation encephalopathy. There was no apparent correlation with dysfunction of the hypothalamohypophyseal axis. PMID- 2891072 TI - Functional supersensitivity to the alpha 1-adrenoceptor agonist after repeated treatment with antidepressant drugs is not conditioned by beta-down-regulation. AB - The effect of repeated administration of desipramine, and the (+)- and (-) enantiomers of oxaprotiline (10 mg/kg i.p., twice daily for 14 days) on the binding of beta- and alpha 1-adrenoceptors in the cortex of the rat brain were studied. The functional consequences of such treatment were measured in a behavioural model, involving the exploratory activity of rats in response to administration of the alpha 1-agonist phenylephrine. Desipramine and (+) oxaprotiline decreased the binding of [3H]dihydroalprenolol ([3H]DHA) to beta adrenoceptors in the cortex, did not change the binding of [3H]prazosin to alpha 1-adrenoceptors, but enhanced behavioural responses to phenylephrine. A behavioural facilitation was also observed after administration of (-) oxaprotiline, a substance which does not change the binding of [3H]DHA. These results indicate that a functional supersensitivity to the alpha 1-adrenoceptor agonist, after repeated treatment with antidepressants is not conditioned by beta down-regulation. PMID- 2891073 TI - Thyrotrophin releasing hormone degradation by rat synaptosomal peptidases: production of the metabolite His-Pro. AB - The dipeptide, His-Pro, is the major product of the degradation of TRH by rat synaptic membranes in vitro. A small amount of His-Pro is also formed from TRH by the synaptosomal soluble fraction. From inhibitor studies, the main route to His Pro appears to involve removal of the pGlu residue by membrane-bound metal dependent pyroglutamylaminopeptidase followed by deamidation. The deamidation step is not mediated by proline endopeptidase (EC3.4.21.26) nor dipeptidylpeptidase-IV (EC3.4.14.5) since it is insensitive to bacitracin and diprotin-A, and may therefore involve a novel membrane-bound TRH metabolizing enzyme. His-Pro is degraded rapidly by the soluble synaptosomal fraction, presumably by prolidase (EC3.4.13.9) and more slowly by the synaptic membrane fraction. PMID- 2891074 TI - Rat brain PCP receptors: alterations in binding parameters following chronic administration of opiate agonists and antagonists. AB - Phencyclidine (PCP) is a widely abused drug of the arylcyclohexylamine class which is capable of producing symptoms of acute psychosis in man. PCP interacts with a specific CNS receptor, for which a putative endogenous peptide ligand has been identified. We have investigated whether PCP receptor binding parameters are modulated by activity in central opiate pathways. We have found that chronic administration of both an opiate agonist (etonitazene) and an opiate antagonist (naloxone) are able to decrease the affinity of the PCP receptor for TCP, a thienyl derivative of PCP. Furthermore, naloxone, but not etonitazene, resulted in a significant increase in the Bmax of TCP binding to the PCP receptor. These results suggest that neural activity mediated by CNS opioids systems is capable of affecting the binding parameters of the PCP receptor. PMID- 2891075 TI - Influence of protease inhibitors on the antidepressant activity of oxytocin. AB - Both in the behavioral despair test and in the learned helplessness test, the antidepressant-like activity of oxytocin (0.500 mg/Kg i.p.) was prevented by the administration of a protease inhibitor (EACA, 400 mg/Kg i.p.; pepstatin, 0.1 mg/Kg i.p.). On the other hand, the linear tripeptide tail of oxytocin, MIF-1, was inactive in the behavioral despair test, and less active than oxytocin in the learned helplessness test. We conclude that the antidepressant activity of oxytocin is due to its cleavage to some smaller fragment(s) different from MIF-1. PMID- 2891077 TI - Drug influences on learning and memory in aged animals and humans. AB - In this article the effects of neurotransmitter systems or specific drugs on cognitive functions of aged animals and humans are reviewed. While there have been used many different pharmacologic and behavioral approaches to treat and test cognitive deficits in aged animals and geriatric or demented patients, there is still the question of the validity of animal models of human disorders. Attempts are made to show that there are parallels and similarities. These similarities suggest that the neurological and neurochemical changes observed may play common roles in similar behavioral deficits observed in aged animals and humans. PMID- 2891076 TI - Lithium and haloperidol differentially alter the dynorphin A (1-8) and enkephalin levels in the neurointermediate lobe of rat pituitary. AB - Repeated administration of the antimanic drug lithium (4 mEq/kg/day for 2, 4 or 6 days, i.p.) to rats produced a progressive decline and eventual depletion of dynorphin-A (1-8) (DYN) concentration whereas Met5-enkephalin (ENK) was only marginally decreased in the neurointermediate lobe of the pituitary (NIL). Administration of a neuroleptic haloperidol neither affected ENK and DYN levels nor influenced lithium-induced changes. The study reveals that lithium produces a preferential perturbation in the dynorphin system relative to the enkephalin system. These results taken together with other evidence, indicate that dynorphin is possibly coreleased with vasopressin following lithium administration and provide a pharmacological support to the previously described colocalization and corelease of these endogenous peptides in the NIL. PMID- 2891078 TI - An immunohistochemical study of pro-somatostatin-derived peptides in the human brain. AB - The distribution of pro-somatostatin-derived-peptide-positive profiles was examined by indirect immunohistofluorescence in nine post-mortem human brains (age 58-73 years). Three specific antisera were used for this study which recognize, respectively, somatostatin-28, somatostatin-28 (1-12) and somatostatin (1-14). Pro-somatostatin-derived-peptide-positive immunoreactive profiles were observed throughout the neuraxis. Cell bodies were found within archeo-, paleo- and neocortical areas, the subcortical white matter, in the nucleus accumbens, caudate nucleus and putamen, as well as in the hypothalamus, the reticular thalamic nucleus and the reticular formation of the brainstem. Fibers and terminals were seen in the same areas as well as in various thalamic nuclei, in the brainstem and spinal cord. Pro-somatostatin-derived-peptide-positive fibre tracts include the bed nucleus of the stria terminalis, the diagonal band of Broca, the stria medullaris, the inter-thalamic adhesion, the posterior commissure and the spinothalamic tract. Furthermore, differences between human and animal brains were noted and some somatostatin systems reported which may be implicated in certain human neuropathological states. PMID- 2891080 TI - Mismatches between neurotransmitter and receptor localizations in brain: observations and implications. PMID- 2891079 TI - Autoradiographic localization of cerebellar excitatory amino acid binding sites in the mouse. AB - We have investigated the cellular localization of cerebellar excitatory amino acid binding sites in normal mice, in mice deficient in granule cells and, perhaps, stellate, basket and Golgi cells (granuloprival mice) and in mice lacking Purkinje cells. In the molecular layer of normal mouse cerebellum, the quisqualate-sensitive binding sites were the predominant type of excitatory amino acid receptor and there were relatively few N-methyl-D-aspartate or kainate sensitive binding sites. The granule cell layer of normal mice contained a mixture of all 3 types, the N-methyl-D-aspartate-sensitive binding sites being predominant. In the molecular layer of granuloprival mice, the number of quisqualate-sensitive binding sites was increased to 214% of control (P less than 0.01), whereas N-methyl-D-aspartate-sensitive binding sites were decreased to 62% of control (P less than 0.001) and kainate-sensitive binding sites were unchanged. In the granule cell layer of these mice, quisqualate-sensitive binding sites were increased to 200% (P less than 0.01), N-methyl-D-aspartate-sensitive binding sites were decreased to 47% (P less than 0.001) and kainate-sensitive binding sites were decreased to 49% (P less than 0.01 of their respective control values. In the molecular layer of mice lacking Purkinje cells, quisqualate sensitive binding sites were reduced to 29% (P less than 0.001) of control and N methyl-D-aspartate-sensitive binding sites were unchanged. In the granule cell layer of these mice, neither quisqualate nor N-methyl-D-aspartate-sensitive binding sites were changed. These results suggest that (1) quisqualate-sensitive binding sites are located principally on dendrites of Purkinje cells and that they up-regulate after deafferentation; (2) N-methyl-D-aspartate-sensitive binding sites are located on granule cells and, perhaps, stellate, basket and Golgi cells, and (3) kainate binding sites are located on cell bodies of granule and, perhaps, Golgi cells. PMID- 2891081 TI - Feedback inhibition of opioid peptide release in the hypothalamus of the rat. AB - Corticotropin-releasing factor initially stimulates the release of beta-endorphin and dynorphin from rat hypothalamic slices in vitro; with time, in the continued presence of corticotropin-releasing factor, the release of both these peptides declines. The studies described here were undertaken to test whether this decline could be due to the operation of inhibitory feedback mechanisms associated with the function of the opioidergic neurons. When the opioid receptor antagonist naloxone was added to the superfusion medium in the presence of corticotropin releasing factor, the time-related decrease in opioid release was not observed. Potassium ions also caused an increase, followed by a decrease, in opioid peptide release, and naloxone also prevented the latter from occurring. In addition, naloxone on its own, produced a Ca2+-dependent increase in the non-stimulated release of beta-endorphin and dynorphin, and this action was resistant to tetrodotoxin. These findings suggest that opioid receptors mediate inhibitory feedback effects upon the secretory activity of beta-endorphin and dynorphin neurons in the hypothalamus. PMID- 2891082 TI - Methamphetamine-induced reduction in D1 and D2 dopamine receptors as evidenced by autoradiography: comparison with tyrosine hydroxylase activity. AB - As determined by autoradiographic techniques, multiple high doses of methamphetamine elicited a reduction in dopamine receptor population (both D1 and D2) in several areas of the rat central nervous system. D1 receptors were labeled with the D1-selective antagonist, [3H]SCH 23390, and D2 receptors were labeled with the D2-selective neuroleptic, [3H]sulpiride. Scatchard analysis, obtained from saturation data in caudate-putamen, indicated that the receptor alterations were due to a decrease in the number of receptors (Bmax) without an apparent change in affinity (Kd). A time course demonstrated that five doses of methamphetamine were required to elicit significant changes in receptors in most brain areas examined. The onset of the receptor alterations in various brain regions correlated with the development of methamphetamine-induced depression of striatal tyrosine hydroxylase activity. In most brain areas, the dopamine receptors returned to normal within 7 days following methamphetamine. PMID- 2891083 TI - Brain glutamate deficiency in amyotrophic lateral sclerosis. AB - Amino acid contents were measured in autopsied brains of eight patients with the sporadic form of amyotrophic lateral sclerosis (ALS) and in brains of control subjects dying without neurologic or psychiatric disease. Glutamic acid content was reduced in most brain regions and in the cervical cord in the ALS patients, while glutamine contents were normal. Taurine contents were increased, and gamma aminobutyric acid contents were decreased in some brain regions in the ALS patients. The brain glutamate deficiency in ALS is unexplained, but insufficient production or release of this excitatory neurotransmitter might have important secondary effects on motor neurons. PMID- 2891084 TI - [Surgical treatment of gastroduodenal ulcer disease. Our experience after the advent of H2-antagonist drugs]. PMID- 2891085 TI - [Influence of H2-blocking drugs on the surgical therapy of peptic ulcer]. PMID- 2891086 TI - [Influence of anti-H2-receptors on the surgery of peptic ulcer]. PMID- 2891087 TI - [Peptic ulcer: changes in the surgical approach after the introduction of H2 antagonists in clinical practice]. PMID- 2891088 TI - Immunohistochemical evidence for the coexistence of cholinergic and catecholaminergic phenotypes in neurones of the vagal motor nucleus in the adult rat. AB - Catecholaminergic nerve cell bodies have been recently identified in the rat spinal cord. They lie in the rostral cervical segments and at the lumbosacral junction. Among them, many are located in parasympathetic areas. This finding led us to investigate the interactions between these catecholaminergic neurones and the cholinergic ones. To address this question, we performed sequential immunocytochemical detection of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) in the same sections. We could then identify the co-expression of both TH and ChAT-like immunoreactivities (LI) in some perikarya of the cervical spinal cord and medulla oblongata. Such cells are located in the caudal extension of the dorsal motor nucleus of the vagus nerve (DMNX) as well as in the caudal part of the medullary DMNX itself. Such a co-expression of TH-LI and ChAT LI could not be found in the lumbosacral region, another parasympathetic territory where cell bodies displaying TH-LI were intermingled with those containing ChAT-LI. This is one of the first demonstrations of the co-existence of catecholaminergic and cholinergic phenotypes in some neurones of the adult mammalian nervous system. These observations also support the presence of catecholaminergic efferents within the vagus nerve. PMID- 2891089 TI - Effects of repeated systemic administration of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) on striatal tyrosine hydroxylase activity in vitro and tyrosine hydroxylase content. AB - We examined both in vitro tyrosine hydroxylase (TH) activity and TH content determined by a new enzyme immunoassay in the mouse striatum after repeated systemic injection of MPTP. Repeated systemic administration of MPTP to mice (30 mg/kg per day, subcutaneously for 8 days) caused an approximately 65% decrease of both TH activity and TH content in the striatum. The intensity of immunohistochemical staining of TH protein in the striatum was also reduced in MPTP-treated mice. These results indicate that the reduction of TH activity in vitro after the repeated administration of MPTP is due to reduction of TH protein as a result of nerve degeneration. PMID- 2891090 TI - Tyrosine hydroxylase-immunoreactive neurons in the human cerebral cortex: a novel catecholaminergic group? AB - Tyrosine hydroxylase-like immunoreactive (TH-IR) neurons with morphological features of interneurons were found throughout the human cerebral cortex. Quantitative estimates in 14 different cytoarchitectonic areas revealed a specific regional distribution pattern, neurons being less dense in primary cortical areas and denser in higher order associative areas and some limbic related areas. A partial relationship was noted between the density of labeled neurons and that of the known dopaminergic innervation. The role of the cortical TH-IR neurons in catecholaminergic function, however, remains unclear since the presence of other catecholaminergic synthesizing enzymes, dopamine-beta hydroxylase and DOPA decarboxylase, could not be demonstrated at their level. Similar neurons have been observed transiently in the rodent cortex during development; their persistence and topographical extension in the human brain warrants further study on their possible functional role. PMID- 2891091 TI - Effects of dynorphin1-13 on cardiac rhythm and cyclic adenosine monophosphate (cAMP) levels in the isolated perfused rat heart. AB - We have studied the effects of dynorphin1-13 on cardiac rhythm and cAMP levels in the isolated perfused rat heart. The standard Langendorff isolated heart preparation was used. The myocardial cAMP levels and the incidence of cardiac arrhythmias were determined after injection of dynorphin1-13. Dynorphin1-13 caused simultaneously cardiac arrhythmias and an increase in myocardial cAMP levels in a dose-dependent manner, and both effects were antagonized by naloxone. Further studies are needed to determine whether myocardial cAMP mediates the dynorphin-induced cardiac arrhythmias. PMID- 2891092 TI - Problems with the use of the toe-spreading reflex in rats as an assay in nerve regeneration studies. AB - Stages in the return of the toe-spreading reflex after sciatic nerve injury were examined using the rat. It was found that the earliest stages in the return of the reflex do not indicate nerve regeneration, but rather reflect the development of adrenalin sensitivity in denervated muscles. Probably systemic adrenalin released during the reflex-testing procedure causes muscle contractions which imitate a nerve-induced toe-spread reflex. PMID- 2891093 TI - Possible presence of [3H]glutathione (GSH) binding sites in synaptic membranes from rat brain. AB - Reduced as well as oxidized forms of glutathione exhibited a significant displacement of the specific binding of [3H]L-glutamic acid (Glu), a potential candidate for the central excitatory neurotransmitter, to the rat brain synaptic membranes. In order to elucidate these findings, an attempt was made to determine whether or not the synaptic membranes contained the binding sites for this peptide using [3H]glutathione (GSH) as a ligand. The specific binding activity was detected in the synaptic membranous preparations and found to be dependent on the incubation temperature and incubation time. The binding reached a plateau within 60 min of incubation at 2 degrees C and 30 degrees C. [3H]GSH binding increased linearly with increasing concentrations of membranous proteins employed. Scatchard analysis revealed that the binding sites consisted of two separate independent components rather than being comprised of a single constituent. A significant and concentration-dependent displacement of the binding was induced not only by the addition of GSH, but also by the inclusion of some GSH derivatives without SH-moiety, such as the oxidized form of glutathione, S-methyl-glutathione and S-hexyl-glutathione. The binding was also significantly inhibited by various alpha- and gamma-peptides containing L-Glu, but not by those containing D-Glu. Amongst 4 different agonists and antagonists used for the subclassification of the central Glu receptors, an agonist, quisqualic acid, and an antagonist, 2-amino-4-phosphonobutyric acid, exhibited a significant inhibition of the binding at the highest concentration employed. These results suggest that the rat brain synaptic membranes may contain structure-selective, temperature-dependent, high affinity and saturable binding sites for glutathione. PMID- 2891094 TI - Reversal potentials of rod horizontal cell responses in the carp retina. PMID- 2891095 TI - Neuromodulators in the retina: an immunohistochemical analysis. PMID- 2891097 TI - Retinal arteriovenous shunts in Takayasu disease. AB - The authors followed up on a series of 24 eyes in 12 patients with Takayasu disease in its moderate to advanced stage over the past 10 years. They paid particular attention to arteriovenous shunt formation in the retina. The authors could identify two types of arteriovenous shunts based on rapid sequence fluorescein angiography. In six eyes, arteriovenous shunts had formed at arteriovenous crossings through direct communication of arterial and venous lumen in the midperipheral retina. In 22 eyes, arteriovenous shunts had formed consequent to dilation of capillaries, formation of preferential channels, and obliteration of neighboring capillaries. These two types seemed to be basic patterns of discrete arteriovenous shunts that characterize Takayasu disease in its advanced stage. PMID- 2891096 TI - Effect of some putative transmitters on amacrine cells and on spreading depression potential. PMID- 2891098 TI - Lymphoma 1987. An interim approach to diagnosis and classification. AB - When immunophenotyping is used for diagnosis, it is essential to use panels of antibodies, rather than a single marker for a specific tumor type. There is virtually no single marker that is absolutely diagnostic and completely reliable for any particular neoplasm. For the most important clinical differential diagnoses--reactive versus neoplastic lymphoid lesions and lymphoma versus nonlymphoid tumor--relatively simple panels of antibodies are usually sufficient. In the former situation, immunoglobulin heavy and light chains (G, M, kappa, lambda) and a pan-T-cell antibody (Leu-4) will usually provide the answer. For the latter circumstance, kappa and lambda, a pan-leukocyte antibody, a pan-B-cell (B1), and a pan-T-cell antibody (Leu-4) along with cytokeratin constitute the initial panel. Further subclassification of lymphomas and leukemias can proceed using other antibodies as indicated in the preceding specific sections on the lymphomas. The use of specific antibodies for nonlymphoid tumors will be dictated by the morphologic appearance of the tumor. These may be used as a second panel if the initial screening does not establish a diagnosis of lymphoma. Performing and interpreting immunohistologic studies requires experience, and probably should not be attempted by laboratories that do not encounter a large number of lymphomas. Frozen tissue can be obtained and stored at -20 degrees for a few days; if immunohistologic studies are deemed necessary, the frozen tissue can be sent on dry ice to a reference laboratory. In preparing biopsy specimens for immunohistologic studies, and in interpreting the results of these studies, it is necessary to bear in mind the fact that morphology remains the most important tool for the diagnosis and subclassification of hematologic neoplasms. Obtaining tissue for marker studies should not be permitted to interfere with adequate morphologic examination. Similarly, artifacts and technical problems can occasionally lead to misleading results; the immunohistologic studies must be interpreted in light of the case as a whole, and should never be allowed to contradict common sense. PMID- 2891099 TI - [Changes in the reactivity of the venous section of the systemic vascular bed to the administration of vasoactive substances in experimental hypertension]. PMID- 2891100 TI - Mucoid Pseudomonas aeruginosa resists nonopsonic phagocytosis by human neutrophils and macrophages. AB - Mucoid Pseudomonas aeruginosa is an important respiratory pathogen in patients with cystic fibrosis, and once acquired is virtually impossible to eradicate. Although mucoid P. aeruginosa is generally believed to be resistant to phagocytosis, the mechanism is not understood fully. We studied the nonopsonic phagocytosis by human neutrophils or macrophages of eight mucoid/nonmucoid P. aeruginosa pairs (three isogenic and five "wild-type"). Mucoid strains were relatively resistant to nonopsonic phagocytosis but the nonmucoid types were phagocytosis-susceptible as assessed by visual inspection and chemiluminescence assays. The mucoid and nonmucoid variants had equal numbers of pili but different surface characteristics as determined by biphasic partitioning in polyethylene glycol and dextran. The mucoid exopolysaccharide of mucoid strains appears to alter the surface characteristics of P. aeruginosa thereby rendering them resistant to nonopsonic phagocytosis. The resistance of mucoid variants of P. aeruginosa to nonopsonic phagocytosis may provide a survival advantage to these bacteria early in the course of pulmonary infection before opsonic antibody and complement are present in respiratory secretions. PMID- 2891101 TI - Ascendency of the black bottle (activated charcoal). PMID- 2891102 TI - Cholecystokinin (CCK8) regulates glucagon, insulin, and somatostatin secretion from isolated rat pancreatic islets: interaction with glucose. AB - The effect of CCK8 on glucagon, insulin and somatostatin release and its interaction with glucose was studied in freshly isolated rat pancreatic islets. While glucose alone inhibited glucagon secretion [half-maximal effect (EC50) = 4.6 mM], glucose in the presence of 10 nM CCK8 increased glucagon release (EC50 = 6.9 mM). This effect of CCK8 was dose-dependent at 11.1 mM glucose (EC50 = 1.0 nM). The dose-response curve for glucose on insulin secretion was shifted to the left by 10 nM CCK8; the EC50 of glucose was 11.6 and 9.3 mM in the absence and presence of CCK8, respectively. Glucose alone enhanced somatostatin release; this glucose-induced release was further increased by 10 nM CCK8. Our data indicate that first, CCK8 is able to reverse the inhibitory effect of glucose on glucagon secretion, second, CCK8 sensitizes the beta cell to the insulinotropic effect of glucose, and third, CCK8 enhances the effect of glucose on somatostatin release. PMID- 2891104 TI - An anonymous single-copy clone, pC63, from chromosome 17q23-qter identifies a frequent RFLP [HGM9 No. D17S21]. PMID- 2891103 TI - Cloning and characterization of a human ribosomal protein gene with enhanced expression in fetal and neoplastic cells. AB - Hepatocellular carcinoma is strongly associated with hepatitis B virus carrier patients who usually have HBV sequences integrated in the chromosomal DNA of liver cells. To assess the possible effects of HBV regulatory sequences (e.g., the enhancer) on expression of neighboring host genes we have screened for cellular genes that are both overexpressed and adjacent to integrated HBV sequences in hepatocellular carcinoma cells. The cloned cDNA for one such gene encodes a protein similar to the E. coli L-3 ribosomal protein which is thought to play a role in mRNA binding to the ribosome. The protein encoded by the cDNA localizes to the nucleolus and is also found in ribosomes; possibly it is the mammalian homologue of L-3 (MRL3). The expression of MRL3 is higher in colon carcinoma and lymphoma cell lines than in normal liver, placenta and diploid fibroblasts, and is also higher in fetal than in adult liver. Therefore, MRL3 overexpression seems to be a property of rapidly dividing cells and is not directly linked to oncogenesis. PMID- 2891105 TI - Cosmid 1-26 defines four RFLPs on chromosome 17q23-qter [HGM9 No. D17S20]. PMID- 2891106 TI - Identification and mapping of RFLPs for human tissue factor (HTF) to chromosome 1p. PMID- 2891107 TI - A second Xba I polymorphic site within the human von Willebrand factor (vWF) gene. PMID- 2891108 TI - Two additional RFLPs at the D4S10 locus, useful for Huntington's disease (HD) family studies. PMID- 2891109 TI - Bgl II RFLP at the human erythrocyte/HepG2-type glucose transporter (GLUT) locus on chromosome 1. PMID- 2891110 TI - Hind III RFLP in the lipoprotein lipase gene, (LPL). PMID- 2891111 TI - A new TaqI polymorphism detected by the cDNA encoding amyloid beta protein of Alzheimer's disease. PMID- 2891112 TI - RFLP of the human placental alkaline phosphatase gene (PLAP). PMID- 2891113 TI - An anonymous genomic probe (p lambda KP20.1) detects a multi-allelic locus on chromosome 19 (D19S25). PMID- 2891114 TI - Autoantibody to the proliferating cell nuclear antigen neutralizes the activity of the auxiliary protein for DNA polymerase delta. AB - Two murine monoclonal antibodies to the proliferating cell nuclear antigen (PCNA), a rabbit anti-N-terminal peptide antibody and human auto-antibody to PCNA reacted with the auxiliary protein for DNA polymerase delta from fetal calf thymus following SDS-polyacrylamide gel electrophoresis, confirming the identity of PCNA and the auxiliary protein. Undenatured auxiliary protein was immunoprecipitated by the human autoantibody, but not by the monoclonal antibodies, which were raised to SDS-denatured PCNA, nor by the anti-N-terminal peptide antibody, suggesting that the epitopes recognized by both the monoclonal antibodies and the anti-peptide antibody are not exposed in the native protein. The human anti-PCNA autoantibody neutralized the activity of the auxiliary protein for DNA polymerase delta, but did not inhibit the activity of pol delta itself. The ability of pol delta to utilize template/primers containing long stretches of single-stranded template was inhibited by the anti-PCNA autoantibody, whereas the activity of pol alpha on such templates was not affected, confirming the specificity of the auxiliary protein for pol delta. The ability of PCNA, a cell cycle-regulated protein, to regulate the activity of pol delta suggests a central role for pol delta in cellular DNA replication. PMID- 2891115 TI - Sph I restriction fragment length polymorphism on human chromosome 16 detected with an APRT gene probe. PMID- 2891116 TI - Multi-allelic RFLP for M27 beta, an anonymous single copy genomic clone at Xp11.3 Xcen [HGM9 provisional no. DXS255]. PMID- 2891117 TI - Multiple RFLPs at the human apolipoprotein D (APOD) locus. PMID- 2891119 TI - Isolation and mapping of a polymorphic DNA sequence pMHZ14 on chromosome 1p (D1S60). PMID- 2891118 TI - A complex Hind III polymorphism in the human apolipoprotein-B gene (APOB). PMID- 2891120 TI - Isolation and mapping of a polymorphic DNA sequence pEKH7.4 to chromosome 1 (D1S65). PMID- 2891121 TI - Isolation and mapping of a polymorphic DNA sequence for NRAS pMCR3 on chromosome 1. PMID- 2891122 TI - Lipophilicity, hydrophilicity, and the central nervous system side effects of beta blockers. AB - One of the attributes of beta-adrenergic blocking agents that has distinguished these drugs from each other is degree of lipophilicity. While this feature may play a role in facilitating passage across the blood-brain barrier, it is essential to realize that crossing the barrier is not necessarily synonymous with the ability to cause central nervous system (CNS) effects. Several studies have found some degree of CNS side effects, particularly tiredness and fatigue, with atenolol, a hydrophilic beta blocker. Pindolol, a moderately lipophilic beta blocker, has been reported to cause greater disturbances on electroencephalogram (EEG) than propranolol, the most highly lipophilic beta blocker. The investigational agent bevantolol exhibits a moderate degree of lipophilicity and a low frequency of CNS side effects. Drug-induced increases in plasma catecholamine levels, the possible saturation of CNS receptor sites at relatively low drug levels, and the specific structural details of beta-blocker molecules have been suggested as possible contributory factors in determining the degree of CNS effects. PMID- 2891123 TI - Beta-blocker therapy for hypertension. Considerations in selecting the most appropriate agent. PMID- 2891124 TI - Use of antipsychotic drugs in depression. Problems and opportunities. AB - Antipsychotic drugs have an important place in pharmacologic treatment of depression. Major depression with psychotic features responds poorly to treatment if an antipsychotic is not used in addition to an antidepressant; however, an antipsychotic confers no additional benefit in nonpsychotic depression. Antipsychotic drugs do have significant short- and long-term side effects, including pseudoparkinsonism, dystonia, akathisia, and tardive dyskinesia. The possibility of a good therapeutic response with minimal side effects can be increased if psychotic depression is diagnosed accurately and the antipsychotic is prescribed according to established clinical guidelines. PMID- 2891125 TI - Medical genetics for clinicians. 1. Recent advances in diagnostic technology. AB - During the last 15 years, the potential for diagnosis and treatment of genetic disorders has rapidly expanded. In general, patients with multisystem abnormalities that include retarded physical growth and delayed development are candidates for chromosome analysis. Because failure to consider a genetic cause for a disorder can be disastrous, physicians need to familiarize themselves with genetic principles and new genetic technology. PMID- 2891126 TI - Critical review of clinical trials in senile dementia--I. PMID- 2891127 TI - Somatostatin analogue SMS 201-995 long term therapy for vipoma. AB - The definitive treatment of a pancreatic tumour secreting vasoactive intestinal polypeptide is surgical removal of the tumour, but when curative resection is not possible symptomatic treatment of the endocrine hyperfunction is important. Streptozotocin, although effective for palliation, can involve unpleasant side effects. We report the long term use of subcutaneous somatostatin analogue SMS 201-995 in an elderly man presenting with severe watery diarrhoea and anaemia due to a pancreatic vipoma. Good symptomatic improvement has been achieved with no side effects over a period of 24 months. We suggest there is a use for subcutaneous SMS 201-995 in elderly patients with inoperable pancreatic gut hormone producing tumours with metastases and in those where surgery would carry a high operative risk. PMID- 2891128 TI - Influence of a wheat diet on mortality of broiler chickens associated with necrotic enteritis. AB - In an experiment to determine methods of incorporating soft winter wheat into broiler diets, a significant increase in mortality was observed in broilers fed wheat in crumbled diets. This increase in mortality was associated with necrotic enteritis with Clostridium perfringens indicated as the causative pathogen and complicated by a coccidiosis outbreak. When yellow corn was used in the diet, mortality was 2.9%. Use of all wheat, ground with a hammer mill, increased mortality to 28.9%. However, roller mill-ground wheat diet resulted in a mortality of 18.1%. When the grain component was approximately 50% wheat and 50% corn, mortality was 12.6% for broilers fed hammer mill-ground wheat and 3.4% for roller mill-ground wheat. Grain and feed were tested for several mycotoxins. Low levels of deoxynivalenol were found in both corn and wheat diets, but no differences between the corn and wheat-based diets were found that would explain the incidence of enteritis. PMID- 2891129 TI - Neurotransmitters and pain control. PMID- 2891131 TI - The role of nonopioid peptides in pain. PMID- 2891132 TI - Gastro-intestinal hormones. PMID- 2891130 TI - Functional aspects of multitransmitter neurons. Studies of interactions among pro opiomelanocortin products. PMID- 2891133 TI - Selective D1 and D2 receptor manipulation in Cebus monkeys: relevance for dystonia and dyskinesia in humans. AB - Selective D1 and D2 dopamine (DA) antagonists and agonists were given to 4 Cebus monkeys who had previously received haloperidol treatment for 4 years. SCH 23390 (a selective D1 antagonist) and raclopride (a selective D2 antagonist) induced identical syndromes consisting of dystonia and oral dyskinesia. Biperiden (an anticholinergic drug) and LY 171555 (a selective D2 agonist) completely antagonized the dystonia and dyskinesia induced by SCH 23390 as well as raclopride. The combined treatment with LY 171555 and SCH 23390 (but not LY 171555 and raclopride) caused pronounced sedation. LY 171555 induced repetitive movements of head, legs and trunk, but no oral dyskinesia. SKF 38393 (a partial D1 agonist) caused slight sedation, minimal oral dyskinesia and a significant reduction in D2 agonist-induced repetitive movements. PMID- 2891134 TI - A DNA sequence of 15 base pairs is sufficient to mediate both glucocorticoid and progesterone induction of gene expression. AB - To define the recognition sequence of the glucocorticoid receptor and its relationship with that of the progesterone receptor, oligonucleotides derived from the glucocorticoid response element of the tyrosine aminotransferase gene were tested upstream of a heterologous promoter for their capacity to mediate effects of these two steroids. We show that a 15-base-pair sequence with partial symmetry is sufficient to confer glucocorticoid inducibility on the promoter of the herpes simplex virus thymidine kinase gene. The same 15-base-pair sequence mediates induction by progesterone. Point mutations in the recognition sequence affect inducibility by glucocorticoids and progesterone similarly. Together with the strong conservation of the sequence of the DNA-binding domain of the two receptors, these data suggest that both proteins recognize a sequence that is similar, if not the same. PMID- 2891135 TI - Human placental Na+,K+-ATPase alpha subunit: cDNA cloning, tissue expression, DNA polymorphism, and chromosomal localization. AB - A 2.2-kilobase clone comprising a major portion of the coding sequence of the Na+,K+-ATPase alpha subunit was cloned from human placenta and its sequence was identical to that encoding the alpha subunit of human kidney and HeLa cells. Transfer blot analysis of the mRNA products of the Na+,K+-ATPase gene from various human tissues and cell lines revealed only one band (approximately 4.7 kilobases) under low and high stringency washing conditions. The levels of expression in the tissues were intestine greater than placenta greater than liver greater than pancreas, and in the cell lines the levels were human erythroleukemia greater than butyrate-induced colon greater than colon greater than brain greater than HeLa cells. mRNA was undetectable in reticulocytes, consistent with our failure to detect positive clones in a size-selected (greater than 2 kilobases) lambda gt11 reticulocyte cDNA library. DNA analysis revealed a polymorphic EcoRI band and chromosome localization by flow sorting and in situ hybridization showed that the alpha subunit is on the short arm (band p11-p13) of chromosome 1. PMID- 2891136 TI - Genetic linkage map of human chromosome 7 with 63 DNA markers. AB - High-density genetic maps of individual human chromosomes will permit accurate localization of disease-associated genes and provide signposts that will be useful in the construction of physical maps. We have constructed a genetic map of chromosome 7 with 63 polymorphic DNA markers by using segregation data from 23 three-generation families and recently developed multilocus linkage-analysis techniques. The map spans 250 centimorgans in females and 170 centimorgans in males, with much of the difference being concentrated in a few intervals. The density and informativeness of the markers are such that there is a high probability of detecting linkage to any disease gene on this chromosome for which 20 phase-known meioses are available. PMID- 2891137 TI - Subcellular compartmentalization of 1-methyl-4-phenylpyridinium with catecholamines in adrenal medullary chromaffin vesicles may explain the lack of toxicity to adrenal chromaffin cells. AB - Cultures of bovine adrenomedullary chromaffin cells accumulated 1-methyl-4 phenylpyridinium (MPP+) in a time- and concentration-dependent manner by a process that was prevented by desmethylimipramine. The subcellular localization of the incorporated [methyl-3H]MPP+ was examined by differential centrifugation and sucrose density gradient fractionation and was found to be predominantly colocalized with catecholamines in chromaffin vesicles, and negligible amounts were detected within the mitochondrial fraction. When chromaffin cell membranes were made permeable with the detergent digitonin in the absence of calcium, there was no increase in the release of [3H]MPP+, indicating that there is negligible accumulation of the neurotoxin in the cytosol. Simultaneous exposure to digitonin and calcium induced cosecretion of MPP+ and catecholamines. Stimulation of the cells with nicotine released both catecholamines and MPP+ at identical rates and percentages of cellular content in a calcium-dependent manner. Last, when cells were incubated with MPP+ in the presence of tetrabenazine (an inhibitor of vesicular uptake), the chromaffin cell toxicity of MPP+ was potentiated. We submit that the ability of the chromaffin cells to take up and store MPP+ in the chromaffin vesicle prevents the toxin's interaction with other structures and, thus, prevents cell damage. As an extension of this hypothesis, the relative resistance of some brain monoaminergic neurons to the toxic actions of 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine may result from the subcellular sequestration of MPP+ in the storage vesicle. PMID- 2891138 TI - Molecular cloning and analysis of the regulation of nit-3, the structural gene for nitrate reductase in Neurospora crassa. AB - The nit-3 gene of Neurospora crassa encodes the enzyme nitrate reductase and is regulated by nitrogen catabolite repression and by specific induction with nitrate. The nit-3 gene was isolated from a cosmid-based genomic library by dual selection for benomyl resistance and for the ability to complement a nit-3 mutant strain using the sibling-selection procedure. The nit-3 gene was subcloned as a 3.8-kilobase DNA fragment from a cosmid that carried an approximately 40-kilobase N. crassa DNA insert. A restriction fragment length polymorphism analysis revealed that the cloned segment displayed tight linkage to two linkage-group-4 markers that flank the genomic location of nit-3. RNA gel blot analyses of RNA from wild-type and various mutant strains were carried out to examine the molecular mechanism for regulation of nit-3 gene expression. The nit-3 gene was transcribed to give a large mRNA of approximately 3.4 kilobases, the expected size to encode nitrate reductase. The nit-3 gene was only expressed in wild-type cells subject to simultaneous nitrogen derepression and nitrate induction. A mutant of nit-2, the major nitrogen regulatory gene of Neurospora, did not have detectable levels of nit-3 gene transcripts under the exact conditions in which these transcripts were highly expressed in wild type. Similarly, a mutant of nit 4, which defines a minor positive-acting nitrogen control gene, failed to express detectable levels of the nit-3 transcript. Nitrate reductase gene expression was partially resistant to nitrogen repression in a mutant of the nmr gene, which appears to be a regulatory gene with a direct role in nitrogen catabolite repression. Results are presented that suggest that the enzyme glutamine synthetase does not serve any regulatory role in controlling nitrate reductase gene expression. PMID- 2891139 TI - cDNA sequence, protein structure, and chromosomal location of the human gene for poly(ADP-ribose) polymerase. AB - Recently we described a full-length cDNA for the human nuclear enzyme poly(ADP ribose) polymerase. Here, we report the chromosomal localization and partial map of the human gene for this enzyme as well as the complete coding sequence for this protein. The nucleotide sequence reveals a single 3042-base open reading frame encoding a protein with a predicted Mr of 113,135. A comparison of this deduced amino acid sequence with the amino acid sequence of three peptides derived from human poly(ADP-ribose) polymerase revealed a match of 27 amino acid residues. A computer-derived structural analysis of the enzyme and a search for similarities with other proteins confirmed that the polymerase belongs to a subfamily of DNA/NAD-binding proteins and DNA-repair proteins. Possible Zn2+ binding "fingers," a nucleotide-binding fold, and a nuclear transport signal were noted. Additionally, chromosomal mapping has identified polymerase-hybridizing sequences on human chromosomes 1 (the active gene), 13, and 14 (processed pseudogenes). Using the polymerase cDNA as a probe, we also have detected several DNA restriction fragment length polymorphisms in normal humans. PMID- 2891140 TI - Plasminogen activator inhibitor type 1 gene is located at region q21.3-q22 of chromosome 7 and genetically linked with cystic fibrosis. AB - The regional chromosomal location of the human gene for plasminogen activator inhibitor type 1 (PAI1) was determined by three independent methods of gene mapping. PAI1 was localized first to 7cen-q32 and then to 7q21.3-q22 by Southern blot hybridization analysis of a panel of human and mouse somatic cell hybrids with a PAI1 cDNA probe and in situ hybridization, respectively. We identified a frequent HindIII restriction fragment length polymorphism (RFLP) of the PAI1 gene with an information content of 0.369. In family studies using this polymorphism, genetic linkage was found between PAI1 and the loci for erythropoietin (EPO), paraoxonase (PON), the met protooncogene (MET), and cystic fibrosis (CF), all previously assigned to the middle part of the long arm of chromosome 7. The linkage with EPO was closest with an estimated genetic distance of 3 centimorgans, whereas that to CF was 20 centimorgans. A three-point genetic linkage analysis and data from previous studies showed that the most likely order of these loci is EPO, PAI1, PON, (MET, CF), with PAI1 being located centromeric to CF. The PAI1 RFLP may prove to be valuable in ordering genetic markers in the CF-linkage group and may also be valuable in genetic analysis of plasminogen activation-related diseases, such as certain thromboembolic disorders and cancer. PMID- 2891141 TI - Regulation of cAMP content and cAMP-dependent protein kinase activity in airway smooth muscle. PMID- 2891143 TI - Studies on putative neurotransmitters in an animal model of hereditary blindness. PMID- 2891142 TI - Docosahexaenoic acid metabolism and inherited retinal degenerations. PMID- 2891144 TI - Behavioral effects of N-ethyl-3,4-methylenedioxyamphetamine (MDE; "EVE"). AB - Eight male rats were trained to discriminate 2.0 mg/kg N-ethyl-3,4 methylenedioxyamphetamine (MDE) from its vehicle using a two-lever, food motivated operant discrimination task. Once trained, the rats showed a dose dependent decrease in discriminative accuracy following administration of decreased doses of MDE (ED50 = 0.75 mg/kg). Administration of 1.5 mg/kg 3,4 methylenedioxymethamphetamine (MDMA), a recently restricted Schedule I drug, produced 100% MDE-appropriate responding in the MDE-trained rats and decreased discriminative performance was similarly observed following lower doses of MDMA (ED50 = 0.62 mg/kg). The difference in relative potencies of MDE and MDMA in rats is reminiscent of those seen in human abusers who report effective oral psychotomimetic doses. Time-course data indicated that MDE has a fast onset, 100% drug-correct responding 10 min post-injection, and a peak effect between 10-20 min with declining effect at 60-120 min post-administration. These findings along with those of others show a pharmacological similarity between MDE and MDMA. Implications as to the future scheduling of MDE are discussed. PMID- 2891145 TI - Reversal of opioid-induced muscular rigidity in rats: evidence for alpha-2 adrenergic involvement. AB - Compounds from several different pharmacological classes were tested for their ability to reverse the muscular rigidity induced by an intravenous dose of fentanyl that also caused loss of the righting reflex (LOR). Opioid antagonists reversed the entire syndrome--LOR and rigidity but, generally, rigidity could be reversed nonspecifically by doses of compounds that caused LOR by themselves (e.g., CNS depressants). Muscle relaxants and agonists of histamine, which appeared to be acting peripherally, were also effective. On the other hand, serotonergic drugs and dopamine agonists were not. However, dopaminergic antagonists with adrenolytic activity (i.e., chlorpromazine, haloperidol) reversed rigidity, whereas sulpiride did not. Moreover, rigidity reversed by neuroleptics could be restored by piperoxane, an alpha-2 adrenergic antagonist. In addition, clonidine and other alpha-2 agonists selectively reversed only rigidity following systemic or central administration at doses several orders of magnitude lower than other compounds tested. It is proposed that opioid-induced rigidity is reversed by inhibition of sympathoadrenal outflow which can be accomplished selectively, centrally, by alpha-2 agonists. PMID- 2891146 TI - New, man-made N2-fixing systems. AB - The major inputs of fixed N into the global nitrogen cycle are assessed and compared as indicators of both the need for and the likely basis of new, complementary, man-made N2-fixing processes. The development, since 1964, of the purely chemical, highly reactive systems for the reduction of N2, including those driven electro- and photochemically, is traced, along with the parallel efforts to synthesize metal-N2 complexes (the first step in any likely fixation process) and subsequently protonate them to produce hydrazine or ammonia. These experimental approaches are convergent. Successful cycling or catalysing of some of these N2-binding systems has been achieved. The advantages and limitations of the more successful systems are noted. Approaches to this problem via direct modelling of the nitrogenase active site are outlined, as is the one successful use of such complexes in achieving N2 reduction. This wealth of effort on the reductive approaches contrasts vividly with the almost complete absence of research on N2 oxidation. Currently, only a re-evaluation of the arc discharge process is continuing. Finally, the author's studies of the extruded molybdenum containing prosthetic group of nitrogenase, the enzymic N2-reducing site, are described in relation to future N2-fixing systems. PMID- 2891147 TI - The relationships of Uronemus: a carboniferous dipnoan with highly modified tooth plates. AB - Previous accounts of the dentition of the Carboniferous dipnoan Uronemus have stressed the significance of the scattered small denticles. These, together with the marginal teeth and ridges, have been interpreted as primitive characters of the dipnoan dentition shared with three other genera: the Devonian Uranlophus and Griphognathus and the Carboniferous to Permian Conchopoma. Genera with tooth plates have been considered to be a monophyletic group in which tooth plates are a derived character; Uronemus has been excluded from this group in all previous investigations dealing with the significance of the dentition for determining relationships among dipnoans. The macromorphology of the dentition of Uronemus has been re-examined and correlated with the histology of all the dental tissues. Optical study of thin sections and scanning electron microscope study of the adjacent cut surfaces has shown that the hard, wear-resistant dentine of the teeth and ridges is petrodentine. The arrangement, growth, wear and histology of the dental tissues have been compared with those of denticulated and tooth-plated genera. The arrangement of new teeth relative to the tooth ridge, the pattern of wear along the ridge, and the type of dentine and its growth indicate that the dentition of Uronemus is best interpreted as a tooth plate with one long lingual tooth ridge and reduced lateral tooth rows. Therefore the marginal tooth ridges are not considered to be homologous with those of denticulate dipnoans such as Uranolophus. The presence of petrodentine, a tissue type only found in forms with tooth plates, is consistent with the view that the dentition is derived by modification of a radiate tooth plate. The denticles covering restricted regions of the palate and lower jaw are considered to have been a secondary acquisition. The suggestion that Conchopoma is a close relative of Uronemus is not accepted, and possible new relationships have been proposed. New data on Scaumenacia and Phaneropleuron, two other genera previously compared with Uronemus, are presented. Rhinodipterus, a form with elongate lingual ridges, is also discussed. Phaneropleuron is shown to have radiate tooth plates and not a marginal row of conical teeth as previously described. It is proposed that the tooth plate of Uronemus is derived from a dipterid type of plate. A discussion of some of the other factors involved in determining the relationships of the genus is given.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2891148 TI - Comparative morphology, histology and growth of the dental plates of the Devonian dipnoan Chirodipterus. AB - The dental plates of the Devonian lungfish Chirodipterus australis Miles (Osteichthyes; Dipnoi) are shown to have achieved their characteristic morphology by a growth process different from that assumed for the plates of genera such as Dipterus. Each plate was thickened by the addition of layers of bone that also extended the plate labially, thus providing the base on which and into which dentine grew. Distinctive features of the dentition are: (a) labial increase of the dentine mass by the addition of blister-like denticles of simple enamel covered dentine, which is initially ingrown by pleromic dentine and subsequently resorbed and replaced by petrodentine; (b) increase in the midline by a similar process that results in the addition of one (or possibly two) new ridges; (c) resorption of the posterior edge of the pterygoid plates and the posterior and posteromedial edges of the prearticular plates, with subsequent development over the resorbed surfaces of several generations of simple regenerative dentine; (d) resorption and redeposition of pleromic dentine and bone in a triangular region posteromedially on the pterygoid plates; (e) the formation of tuberosities that simulate teeth at a short distance in from the labial edge, by four processes: formation of an undulating plate margin, differential growth of petrodentine (hard compact dentine) within the pulp cavity, differential wear of the petrodentine and the adjacent bone plus pleromic dentine, and slightly greater growth of the petrodentine towards the occlusal surface relative to the adjacent bone and dentine; (f) expansion of the large flat surfaces of the plates by gradual replacement of the bone and dentine at the proximal ends of the furrows and also by the development of linkages of petrodentine across the furrows; (g) development of isolated tuberosities on the flat posterolateral parts of the plates. The petrodentine of the ridges, tuberosities and plateaus of the plates is indistinguishable structurally and in its mode of growth from the petrodentine in extant species of dipnoans. Plates similar to those of C. australis have been observed in Stomiahykus, Archaeonectes, Conchodus, Palaedaphus and Sunwapta, as well as several species usually referred to as Dipterus. Sunwapta may be congeneric with C. australis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2891149 TI - Organization of lumbar spinal outflow to distal colon and pelvic organs. AB - The lumbar sympathetic outflow projects through the lumbar splanchnic, lumbar colonic, and hypogastric nerves (and to a lesser degree through the sacral sympathetic chain and pelvic nerves). It is thought to be involved in the regulation of the storage and evacuation functions of the following three organ systems: lower urinary tract, hindgut, and reproductive organs. In addition, it controls vascular resistance and capacitance. Thus the target tissues of the postganglionic neurons are vascular smooth muscle, visceral smooth muscles, probably secretory epithelia, and also neurons in the enteric nervous system and the pelvic ganglia. The preganglionic neurons are situated in the caudal part of the spinal representation, neurons associated with the colon being located rostral to those associated with the pelvic organs. Most lie medial to the classical intermediolateral cell column that may contain mainly vasoconstrictor neurons. Most (if not all) preganglionic neurons are cholinergic; some also contain an identified peptide. Most of the postganglionic neurons are situated in the inferior mesenteric ganglion (or equivalent structures); again, those projecting to the colon lie rostral to those projecting to the pelvic organs. Others lie in intercalated prevertebral ganglia, in the pelvic plexus, and in sacral paravertebral ganglia. The majority is noradrenergic, and most also contain one or several peptides, the topographical distribution of which appears to characterize functional subgroups of neurons. The terminations of noradrenergic axons in many pelvic organs probably make close contact with both vascular and nonvascular effectors. In the colon, most endings are located in the enteric plexuses. The responses of these organs to electrical stimulation of visceral nerves, and their reflex responses (together with those observed in the efferent axons of visceral nerve trunks) to electrical and natural stimulation of afferent fibers, lead to the general conclusion that several distinct classes of pre- and postganglionic neurons exist. 1) Vasoconstrictor neurons demonstrate ongoing activity with cardiac rhythm and appropriate reflexes to stimulation of cardiovascular afferent receptors and respond only weakly to natural stimulation of visceral receptors. 2) MR neurons respond to visceral stimuli but are not influenced from arterial baro- and chemoreceptors. These show at least two different response patterns consistent with their separate involvement in the reciprocal behavior of the colon and bladder. 3) Other neurons are silent in anesthetized animals and do not respond to any stimuli used thus far.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2891150 TI - Alpha 2-adrenoceptor antagonists and male sexual behavior: II. Erectile and ejaculatory reflexes. AB - Three alpha 2-adrenoceptor antagonists, yohimbine, idazoxan, and imiloxan, all shown to have stimulatory effects on sexual arousal/motivation, were studied to identify their possible effects on the other two major components of male copulatory behavior: erection and ejaculation. Genital reflex ex copula tests were used in order to assess these two responses without the confounding factors of mating behavior. Dose ranges were yohimbine: 0.25-4.0 mg/kg; idazoxan: 1.0-8.0 mg/kg; and imiloxan: 12.5-50.0 mg/kg. Lower doses of two of the drugs significantly enhanced the frequency of erections, while the third (yohimbine) showed a strong trend in that direction. At higher doses, all three alpha 2 antagonists produced significant reductions in the number of rats showing penile reflexes, including both erections and ejaculations. In those rats which did show penile reflexes, higher doses of yohimbine (4.0 mg/kg) inhibited the frequency of erections, while the higher dose of idazoxan showed a trend towards such inhibition. Thus, profound, largely inhibitory effects of these agents were demonstrated at dose ranges which have been shown to enhance sexual arousal. These data indicate that within the nervous system alpha 2-adrenoceptor antagonists can modulate erectile and ejaculatory mechanisms quite independently from effects on arousal/motivation. PMID- 2891151 TI - Alpha 2-adrenoceptor antagonists and male sexual behavior: I. Mating behavior. AB - Three alpha 2-adrenoceptor antagonists yohimbine, idazoxan, and imiloxan were compared by examining the effects of a single injection on male rat copulatory behavior. Dose ranges were: yohimbine: 0.25-8.0 mg/kg; idazoxan: 0.25-8.0 mg/kg; imiloxan: 12.5-50.0 mg/kg. Yohimbine and idazoxan administration produced significant increases in the number of animals copulating to ejaculation and all three drugs increased the rate of copulation as evidenced by reductions in ejaculation latency and intercopulatory interval. Only yohimbine significantly reduced mount latency and postejaculatory interval, but yohimbine and imiloxan significantly reduced intromission latency and idazoxan showed a similar trend. The highest yohimbine dose suppressed sexual activity. A time-course experiment with yohimbine (2.0 mg/kg) and idazoxan (4.0 mg/kg) showed stimulation at 75 min and a trend at 5. To further explore the arousal-stimulating capacity of the two more effective drugs, a mounting test with genital anesthetization was used. Yohimbine but not idazoxan showed marked increases in mounting at 1.0-4.0 mg/kg. Both drugs had a suppressive effect at the highest doses. These data support the involvement of alpha 2-adrenoceptors in the regulation of male sexual behavior, specifically by facilitating sexual arousal, with no effects on ejaculatory threshold, as measured by intromission frequency. Yohimbine is the most globally effective agent and it is likely that factors other than yohimbine's alpha 2 antagonism may play a role in its unique, consistent and broad behavioral effects. PMID- 2891152 TI - [Sex. The twilight of the myth of Adam and Eve?]. PMID- 2891153 TI - Simultaneous bilateral foot reconstruction using a single radial forearm flap. AB - The radial forearm septocutaneous flap is an excellent source of thin tissue with an anatomically consistent network of large vessels that simplify microsurgical transfer. It may be divided into multiple flaps leaving a single donor-site defect. The clinical usefulness of this concept is demonstrated in a single case in which simultaneous coverage of electrical burns of both feet was required. PMID- 2891154 TI - Amebic liver abscess: diagnosis and treatment evaluation with MR imaging. AB - Magnetic resonance images were obtained before and after treatment in 17 patients with 29 amebic liver abscesses. Pretreatment T1-weighted images showed a sharply circumscribed, heterogeneous, low-signal-intensity mass, devoid of normal hepatic tissue and corresponding to the abscess cavity as measured sonographically. T2 weighted images showed the abscess cavity as a hyperintense region and also showed a larger region of hyperintensity extending from the cavity margins to the liver surface, corresponding to edematous but morphologically normal liver tissue. After treatment, the abscess cavity became homogeneously hypointense on T1-weighted images, corresponding to liquefaction of the abscess center. With successful treatment, concentric rings corresponding to (a) an inner margin of inflamed granulation tissue, (b) bands of type I collagen, and (c) the outer margin of atrophic and/or mildly inflamed liver tissue became prominent on T1- and T2-weighted images. T2-weighted images showed rapid resolution of the perifocal hepatic edema. PMID- 2891155 TI - Chromatographic characterization of dynorphin and [Leu5]enkephalin immunoreactivity in guinea pig and rat testis. AB - Tissues of the reproductive tract have been shown to contain mRNAs coding for pro opiomelanocortin (POMC), pro-enkephalin and pro-dynorphin. However, the amounts of immunoreactive opioid peptides in these tissues are low, and in the case of the enkephalins and dynorphin, the molecular species responsible for the immunoreactivities have not been characterized. The chromatographic properties of dynorphin and enkephalin immunoreactivities in extracts of guinea pig and rat testis have therefore been determined. Dynorphin A and dynorphin B immunoreactivity was heterogeneous, with a significant amount attributable to high-molecular-weight forms. About 20% of the dynorphin A immunoreactivity, and about 40% of the dynorphin B immunoreactivity, in guinea pig testis extracts behaved as authentic dynorphin A or B, respectively during fractionation by ion exchange, gel filtration and high-performance liquid chromatography. Both high- and low-molecular-weight forms of [Leu5]enkephalin immunoreactivity were also present, with roughly 50-70% of the immunoreactivity attributable to low molecular-weight forms. In extracts of guinea pig testis only a small part of this immunoreactivity eluted as authentic [Leu5]enkephalin during high performance liquid chromatography. In rat testis most of the low-molecular-weight [Leu5]enkephalin immunoreactivity behaved as the authentic peptide. These results confirm that opioid peptides are produced in guinea pig and rat testis, and demonstrate that immunoreactive forms of the peptides similar to those found in brain and pituitary are present in the tissue. PMID- 2891156 TI - [Testicular autotransplant--microsurgical technic]. PMID- 2891157 TI - [Facilitation of endotracheal intubation with vecuronium after using previous doses for priming neuromuscular transmission]. PMID- 2891158 TI - [Continuous epidural perfusion of morphine by a pump for postoperative analgesia]. PMID- 2891159 TI - [Fazadinium and presynaptic effects]. PMID- 2891160 TI - [Gastrointestinal pathology following orthotopic transplantation of the liver in the pig]. PMID- 2891161 TI - [Effect of beta-adrenergic stimulation on gastric secretion: experimental study in dogs]. PMID- 2891162 TI - Effects of wheat bran on exocrine pancreas secretion in the pig. AB - The aim of this study was to determine the effect of wheat bran consumption on exocrine pancreas secretion in pigs. Sixteen Large-White pigs were divided into two groups. The first group (control) was fed a diet without wheat bran and the second one (experimental) a diet containing 40% wheat bran. After one week the animals were fitted with two permanent fistulae (in the pancreatic duct and the duodenum) and/or with a catheter in a carotid artery. After an 8-day recovery period, pancreatic secretion (volume, protein content and output, chymotrypsin, trypsin, lipase and amylase activities) and plasma levels of some gastro intestinal peptides [secretin, cholecystokinin (CCK), vasoactive intestinal peptide (VIP), somatostatin and pancreatic polypeptide (PP)] were measured over an experimental period of 5 days. The results show that wheat bran intake induced an increase in the volume (+ 115%) and protein output (+ 36%) of the pancreatic juice secreted in a 24-hour period, whereas protein concentration decreased. All enzyme activities were enhanced by wheat bran. The plasma levels of secretin, VIP, somatostatin and PP were higher in the experimental than in the control group. On the contrary, plasma CCK levels were not affected by wheat bran consumption. PMID- 2891164 TI - [Current thinking on the chemical transmission of information in the neuroendocrine system]. PMID- 2891163 TI - Production and evaluation of monoclonal antibodies directed against the K88 fimbrial adhesin produced by Escherichia coli enterotoxigenic for piglets. AB - Fifty murine monoclonal antibodies were produced against a purified preparation of K88ab antigen. Two monoclonal antibodies were selected for further studies together with a monoclonal antibody directed against the c region of K88 (5CA3). Monoclonal antibody K88-13 bound to all K88+ Escherichia coli examined, whereas K88-18 and 5CA3 bound to K88ab+ and K88ac+ strains, respectively. The monoclonal antibodies failed to react with K88+ E coli grown at 18 degrees C or with K88- E coli grown at 37 degrees C or 18 degrees C. Binding of monoclonal antibody K88-13 to K88 antigen was blocked by OK antisera to G7 (O8:K87 K88ab) and Abbotstown (O149:K91 K88ac), whereas absorbed antisera to K88b, c and d had no effect. Monoclonal K88-18 was inhibited by OK G7 antiserum and absorbed antiserum to K88b. One hundred and forty-nine strains of K88+ E coli representing seven somatic O groups were agglutinated by antibody K88-13; 142 of these, from at least six somatic O groups were agglutinated by 5CA3 and the remainder by K88-18. Monoclonal antibody K88-13 bound to cryostat sections of ileum from piglets infected with E coli strains Abbotstown and G7. K88-18 and 5CA3 bound only to sections from piglets infected with G7 and Abbotstown strains, respectively. It is concluded that monoclonal antibody K88-13 recognises an epitope on the a region of K88 while monoclonal antibody K88-18 is directed towards the b region. These monoclonal antibodies together with 5CA3 can be used to routinely identify K88+ E coli isolates. PMID- 2891165 TI - [New concepts of synaptic functioning]. PMID- 2891166 TI - [Environmental hygiene activities in the present century and their reflection in the pages of the Revista Medico-Chirurgicala]. PMID- 2891167 TI - [Fibronectin in pathology]. PMID- 2891168 TI - [Present status and perspectives in immunologic therapy]. PMID- 2891169 TI - [Current data regarding new positive inotropic drugs]. PMID- 2891170 TI - [Treatment of the hypertensive crisis. I]. PMID- 2891171 TI - [Beta adrenergic blockers as anti-arrhythmia agents]. PMID- 2891172 TI - [Socio-professional and familial integration of patients with insulin-dependent diabetes mellitus type I]. PMID- 2891173 TI - [Pharmacokinetics of quinidine following the administration of a single intravenous dose or single and repeated oral doses in human subjects]. PMID- 2891174 TI - [Bidimensional echocardiographic exploration in the evaluation of the sequelae of myocardial infarction and its complications]. PMID- 2891175 TI - [Immunologic abnormalities, quantitative and qualitative, in chronic active liver disease]. PMID- 2891176 TI - [Ultrastructural aspects of cells in Hodgkin's lesions]. PMID- 2891177 TI - [Immunologic changes in patients with urinary infection]. PMID- 2891178 TI - [Beta adrenergic receptor agonists in hospital practice]. PMID- 2891179 TI - Kinetic parameters of tyrosine hydroxylase in the rat's preoptic region during sleep deprivation and recovery induced by ambient temperature. AB - The role of catecholaminergic mechanisms in determining the changes in the rat's preoptic cyclic adenosine monophosphate (cAMP) concentration during sleep deprivation and recovery induced by ambient temperature was investigated in the present study. To this end, the activity of tyrosine hydroxylase, the rate limiting enzyme in catecholamine biosynthesis, was measured in the preoptic region of rats maintained in: (a) control (22 degrees C for 52 h), (b) deprivation (-10 degrees C for 52 h), and (c) recovery (22 degrees C for 4 h after 48 h at -10 degrees C) conditions. The enzyme followed a Michaelis-Menten kinetic. The analysis of substrate-related kinetic parameters (Km and Vmax) did not show any clear-cut difference between experimental conditions, which, as already known, induce both sleep deprivation and recovery in relation to significant cAMP changes. PMID- 2891180 TI - Molecular basis of bacterial adhesion in the oral cavity. AB - The two varieties of fimbriae identified on oral strains of actinomyces have distinct functional properties. The type 1 fimbriae of Actinomyces viscosus T14V mediate attachment to saliva-treated hydroxyapatite. Type 2 fimbriae--on A. viscosus and the only fimbriae detected on A. naeslundii WVU45--are associated with lectin activity. Interaction of these fimbriae with complementary receptors initiates bacterial attachment to Streptococcus sanguis 34 and sialidase-treated epithelial cells and the killing of actinomyces by polymorphonuclear leukocytes (PMNs). Galactose, N-acetylgalactosamine (GalNAc), and related oligosaccharides inhibit these processes, and mutants lacking type 2 fimbriae do not participate in them. The actinomyces lectin is similar to lectins from Ricinus communis and Bauhinia purpurea that agglutinate certain strains of oral streptococci, block attachment of actinomyces to epithelial cells, and inhibit killing of actinomyces by PMNs. The S. sanguis receptor for the actinomyces lectin comprises repeating hexasaccharide units with GalNAc termini. Used as probes, the peanut agglutinin, with specificity for Gal(beta-3)GalNAc, and the lectin from B. purpurea detect a 160-kilodalton (kdal) band in SDS-PAGE-separated epithelial cell extracts and a 100-kdal band in PMN extracts. These may be receptors for type 2 fimbriae. A. viscosus genes encoding subunits of types 1 and 2 fimbriae have been cloned in Escherichia coli; the type 1 subunit is 65 kdal and the type 2 subunit is 59 kdal. Submandibular immunization of mice with a mixture of type 1 and type 2 fimbriae evokes the production of IgA and IgG antibodies in serum and saliva that inhibit in vitro adsorption of A. viscosus to SHA. These antibodies may modulate colonization of teeth by this organism. PMID- 2891181 TI - [Current status of tuberculosis therapy at the 10th Congress of U.S.S.R. phthisiologists. (Kharkov, 1-3 October 1986)]. PMID- 2891182 TI - Effect of somatostatin on liver blood flow and liver metabolic activity in patients with cirrhosis. AB - In a group of 10 patients with cirrhosis, protal hypertension, and previous gastro-intestinal bleedings, hepatic plasma flow, indocyanine green clearance and intrinsic hepatic clearance were determined before and during i.v. infusion of somatostatin (7.5 micrograms/min). The same study protocol was performed in a further seven patients with cirrhosis infused with placebo. All these parameters were significantly decreased by the drug (p less than 0.05; less than 0.01; less than 0.01, respectively) mean decrease being 12, 9 and 8%, respectively, while no significant change occurred in the placebo-infused patients. These data indicate that somatostatin infused at a dose of 7.5 micrograms/min in cirrhotics provokes a slight decrease in hepatic plasma flow and in liver metabolic activity. This effect may contribute to further decrease hepatic removal of harmful substances and may increase systemic concentration of drugs metabolized by the liver. PMID- 2891183 TI - Relative selectivity of different beta-adrenoceptor antagonists for human heart beta 1- and beta 2-receptor subtypes assayed by a radioligand binding technique. AB - The affinity constants of inhibition (Ki values) for both beta 1- and beta 2 receptor subtypes were determined for four different beta-adrenoceptor antagonists by a radioligand binding technique in a human myocardial membrane preparation. The radioligand was the high affinity antagonist [125I]-(-) iodocyanopindolol (ICYP), and the drugs tested were atenolol, metoprolol, ICI 141,292 and ICI 118,551. Different concentrations of the drugs at test were allowed to compete with a constant concentration of ICYP for the specific binding sites (beta-receptors). Ki values for beta 1- and beta 2-receptors for each beta adrenoceptor antagonist were developed from these data by computer calculations. Atenolol and metoprolol were found to differ slightly regarding potency (absolute Ki values) and to be practically equal regarding relative selectivity (approx. 40; i.e. ratio between high and low Ki values), while ICI 141,292 was found to have slightly higher relative selectivity (approx. 60) and much higher potency. All these drugs exhibited highest affinity for the beta 1-receptor population. In contrast, ICI 118,551 exhibited a very high relative selectivity (approx. 300) with highest affinity for the beta 2-receptor subtype. The method represents a good supplement to physiological and clinical examinations of selectivity of beta blockers, and offers several advantages regarding simplicity, specificity and accuracy. PMID- 2891184 TI - Haemodynamic effects of a long-acting somatostatin analogue in patients with liver cirrhosis. AB - The influence of SMS 201-995 (octreotide, Sandostatin), a long-acting somatostatin analogue, on splanchnic haemodynamics was studied in 15 patients with liver cirrhosis and in 5 healthy individuals before, during, and after 60 min of intravenous SMS infusion (25 and 50 micrograms/h, respectively). No adverse effects of the SMS infusion were seen. In the basal state the estimated hepatic blood flow was 1.04 +/- 0.08 l/min (mean +/- SE) in the patients and 1.62 +/- 0.09 l/min (P less than 0.001) in the controls. At 15 min after the beginning of the infusion the blood flow had already decreased by 15-30% (P less than 0.05 0.01). The reduction was more marked in controls than in patients, and it persisted in both groups during and for 60 min after the infusion. Wedged hepatic venous pressure, measured in the patients, was 20 +/- 2 mmHg in the basal state and 18 +/- 1 mmHg during the infusion (P less than 0.05), and it remained at this level for 60 min after the infusion. Free hepatic venous pressure was unchanged throughout the study. Splanchnic oxygen uptake was similar in the two groups in the basal state and remained unaltered during and after SMS infusion. Both heart rate and arterial systolic and diastolic blood pressure remained unchanged during SMS administration. In summary, SMS infusion results in a fall in hepatic blood flow and a slight but significant decrease in wedged hepatic venous pressure, whereas no effect was noted on the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891185 TI - Circulating immunoreactive somatostatin in gastrointestinal diseases. Decrease after vagotomy and enhancement in active ulcerative colitis, irritable bowel syndrome, and duodenal ulcer. AB - The main source of circulating immunoreactive somatostatin (IRS) seems to be the gastrointestinal tract. We therefore investigated plasma IRS in patients with various gastrointestinal diseases. Mean basal IRS oscillated between 46 and 73 pg/ml. A postprandial rise was observed in all patients and age-matched controls. However, the increment was significantly higher in patients with duodenal ulcer (159 +/- 20 pg/ml), active ulcerative colitis (176 +/- 17 pg/ml), and irritable bowel syndrome (194.4 +/- 20.4 pg/ml). Patients with duodenal ulcers who underwent vagotomy showed a decreased postprandial increment (107 +/- 10 pg/ml) when compared with active duodenal ulcer patients. No difference was demonstrable between controls and individuals with gastric ulcer, and patients with inactive ulcerative colitis. These results suggest that vagal innervation plays a role in postprandial IRS stimulation, whereas gastric hyperacidity, acute lesions of the colonic mucosa, and hypermotility of the gastrointestinal tract are associated with an exaggerated postprandial IRS response. Since somatostatin is known to influence many gastrointestinal functions, these variations in circulating IRS concentrations may be of pathophysiologic importance. PMID- 2891186 TI - The use of a long-acting somatostatin analogue in the treatment of advanced endocrine malignancies with gastrointestinal symptoms. AB - Four patients with advanced endocrine malignancies were treated with a somatostatin analogue (SMS 201-995) for palliation of hormone-induced symptoms during 3-6 months. Two had the carcinoid syndrome (one midgut and one foregut), one had medullary thyroid carcinoma and an ectopic ACTH syndrome, and one patient had a metastatic gastrinoma. The carcinoid patients had excellent symptomatic relief with a low dose of the drug, 50 micrograms subcutaneously twice daily, in one case despite progression of tumour disease and biochemical tumour markers. These findings indicate an action of the drug not only on hormonal release but also at peripheral sites. The patient with medullary thyroid carcinoma had relief of gastrointestinal symptoms when the drug dose was increased (100 micrograms twice daily). The levels of ACTH in peripheral blood were reduced, but not the calcitonin levels. The gastrinoma patient had undergone a major pancreatic resection (Whipple procedure) and was treated with omeprazole. SMS 201-995 reduced the peripheral gastrin levels acutely, but during the treatment fasting gastrin values increased, and the tumour growth progressed. Treatment was stopped owing to elevated fasting glucose level, increased steatorrhoea, and clinical attacks of cholangitis. Special attention is advocated for patients with major pancreatic resection and biliary reconstruction, who may be susceptible to physiological effects of somatostatin (or its analogues)--that is, impaired insulin release and decreased motility. PMID- 2891187 TI - [The disseminated endocrine system of man. A contribution of pathology]. AB - The disseminated (or diffuse) endocrine system is composed of many single cells and small groups of cells disseminated in the whole organism, capable of producing biogenic amines and polypeptide hormones. They are also called APUD cells and were first detected in the mucosa of the intestinal tract, where they occur in highest concentration. Carcinoids are tumors of disseminated endocrine cells which sometime retain their hormone-producing capacity. These hormones are key factors in the control of numerous bodily functions; some are transported by way of the bloodstream, while others probably exercise their functions only within the tissue immediately adjacent to the producing cells (paracrine function). It is an interesting fact that almost identical hormones are found within the brain and within the peripheral autonomic nervous system, where they act as neural transmitters. PMID- 2891189 TI - Transmission of AIDS virus. PMID- 2891188 TI - A new prosomatostatin-derived peptide reveals a pattern for prohormone cleavage at monobasic sites. AB - Cleavage of the peptide bonds of preprosomatostatin at basic residues near the carboxyl terminus yields somatostatin-14, somatostatin-28, and somatostatin-28 (1 12). However, little is known about the molecular forms derived from the amino terminal portion of the precursor, even though this part of the prohormone is highly conserved through evolution. By using an antibody against the amino terminus of prosomatostatin, a decapeptide with the structure Ala-Pro-Ser-Asp-Pro Arg-Leu-Arg-Gln-Phe, corresponding to preprosomatostatin (25-34), was isolated from the endocrine portion of the rat stomach, the gastric antrum. The antral decapeptide may represent a bioactive product generated from prosomatostatin after a monobasic cleavage similar to that involved in the formation of somatostatin-28. In fact, a monobasic cleavage requires two basic residues and a domain containing nonpolar amino acids such as alanine or leucine, or both. PMID- 2891190 TI - Quantal release of transmitter is not associated with channel opening on the neuronal membrane. AB - The traditional view that quantal release of neurotransmitter results from the fusion of transmitter-containing vesicles with the neuronal membrane has been recently challenged. Although various alternative mechanisms have been proposed, a common element among them is the release of cytoplasmic transmitter, which, in one view, could occur through large conductance channels on the presynaptic membrane. Six nerve-muscle cell pairs were examined with a whole-cell patch clamp for the presence of such channels that are associated with the production of miniature end-plate potentials. Examination of the neuronal membrane current during the occurrence of 822 miniature end-plate potentials produced no evidence of large channels. Thus it is unlikely that quantal release is mediated by such channels in the neuromuscular junction. PMID- 2891191 TI - Noncovalent and covalent interactions of thrombospondin with polymerizing fibrin. PMID- 2891192 TI - [Reconstructive surgery in post-traumatic soft tissue damage of the lower leg and foot]. PMID- 2891193 TI - [Rapid and sensitive assay of monoamine transmitters and their metabolites in biological samples using high performance liquid chromatography with electrochemical detection]. PMID- 2891194 TI - Neuroendocrine (carcinoid) tumor of the lung and type I multiple endocrine neoplasia. AB - We have described a case of MEN-I in association with a benign pulmonary carcinoid tumor. Two other members of our patient's family also had MEN-I and benign carcinoid or adenomatous lung tumors. Hormonal assays of our patient's carcinoid lesion showed the production of gastrin, gastrin-releasing peptide, neurotensin, and somatostatin, but not serotonin, a hormonal profile distinct from those previously reported in carcinoid lung tumors unassociated with MEN-I. PMID- 2891195 TI - [Changes in the levels of cyclic nucleotides and various neuromediators in alcoholic patients with pulmonary tuberculosis]. PMID- 2891196 TI - Entamoeba histolytica cyst passers--to treat or not to treat? PMID- 2891197 TI - A longitudinal study of asymptomatic carriers of pathogenic zymodemes of Entamoeba histolytica. AB - The value of treating subjects who pass Entamoeba histolytica cysts in their faeces is currently in question. In the endemic Durban area iso-enzyme electrophoresis of E. histolytica isolates indicated that 1% of the asymptomatic population are infected with pathogenic zymodemes. The outcome of these potentially invasive infections was established by means of a longitudinal survey. All subjects had strongly positive serological responses--10% of them developed amoebic colitis while the rest remained asymptomatic and spontaneous cure occurred within 1 year. Infections with pathogenic zymodemes occurred in family units and closely related individuals. Since they were cyst passers, good evidence was obtained for the existence of a carrier state for pathogenic E. histolytica. The value of sero-epidemiological surveys in determining the prevalence of pathogenic E. histolytica in a community was highlighted. Treatment of asymptomatic carriers with pathogenic zymodemes of E. histolytica is as essential as treatment of patients with invasive amoebiasis, and in both cases all contacts of affected individuals must also be treated if they are found to harbour pathogenic zymodemes of E. histolytica in order to ensure control of disease transmission. PMID- 2891198 TI - Takayasu's aorto-arteritis. A report of 11 cases at King Edward VIII Hospital, Durban. AB - Eleven cases of histologically confirmed Takayasu's aorto-arteritis seen at King Edward VIII Hospital, Durban, are presented. The morphological features of the various histological stages are highlighted. The anatomical distribution of lesions is also discussed. PMID- 2891199 TI - Myocardial ischaemia--metabolism and its modification. AB - Ischaemic heart disease (IHD) kills by myocardial failure or by the sudden development of lethal ventricular arrhythmias such as ventricular fibrillation. Impaired coronary flow causes myocardial ischaemia, which acutely predisposes to ventricular fibrillation. If ischaemia is sustained, it may develop into cell necrosis (myocardial infarction). All these clinical manifestations of IHD depend on myocardial metabolic changes which in turn can be modified by pharmacological manipulation such as beta-adrenergic blockade or by reperfusion. The mechanism of reperfusion injury appears to be metabolic in origin, related either to free radicals or excess accumulation of cytosolic calcium. PMID- 2891200 TI - Caudal block for analgesia after paediatric inguinal surgery. AB - Two hundred and eleven children aged 1-5 years were studied after undergoing herniorrhaphy or orchiopexy. In 111 cases a caudal block was used for postoperative analgesia. This was administered immediately after induction of anaesthesia, using bupivacaine 0.25% plain (0.7 ml/kg lean body mass), and was successful in 100 patients. A mean analgesic level (+/- SE) of T9.9 +/- 0.47 was achieved (range L2-T6). In 5 cases no block occurred and in 6 the level was below T12. The other 100 children acted as controls. Behaviour patterns were more restful in the caudal block group on awakening and less opiate was required during the first 5 postoperative hours. No complications resulted. PMID- 2891201 TI - Effect of parathyroidectomy in patients with hyperparathyroidism, Zollinger Ellison syndrome, and multiple endocrine neoplasia type I: a prospective study. AB - This study evaluates prospectively the effect of parathyroidectomy on basal acid output (BAO), maximal acid output (MAO), fasting serum gastrin, secretin stimulated serum gastrin, and sensitivity to antisecretory medication in 10 consecutive patients with primary hyperparathyroidism (PHP), Zollinger-Ellison syndrome (ZES), and multiple endocrine neoplasia type I (MEN-I). After parathyroidectomy, 9 of 10 patients remained normocalcemic, and each had a lower BAO; 6 of 9 no longer had gastric acid hypersecretion (less than 15 mEq/hr). Seven of 9 normocalcemic patients had a lower MAO, and a decrease in fasting serum gastrin. Two patients showed no evidence of ZES, a normal BAO, normal fasting serum gastrin concentration, and a negative secretin response after parathyroidectomy. Parathyroidectomy also reduced the dose of histamine H2 receptor antagonist required to control gastric acid secretion in 60% of patients. After successful parathyroidectomy three patients were studied for drug sensitivity, and each had greater acid inhibition with a given dose of histamine H2-receptor antagonist than preoperatively. One patient remained hypercalcemic after surgery and had no change in BAO, MAO, or gastrin. All patients with postoperative normocalcemia will have a lower BAO, 80% a lower MAO, 80% a decreased fasting serum gastrin, and 33% a negative secretin test. Antisecretory medication dose can be reduced because patients have reduced BAO and increased sensitivity to histamine H2-receptor antagonist. The study supports parathyroidectomy as the initial surgical procedure of choice in patients with PHP, ZES, and MEN-I. PMID- 2891202 TI - Somatostatin analogue inhibition of isolated parietal cell secretion. AB - Somatostatin, somatotropin release-inhibiting factor (SRIF), is a regulatory peptide that has proved to directly inhibit parietal cell acid secretion. However, the therapeutic usefulness of SRIF has been limited by a brief plasma half-life. Several analogues of SRIF that are effective in suppressing acid secretion in vivo have been developed. This study was undertaken to compare the effects of SRIF and two analogues, SMS 201-995 and L-363,568, on in vitro acid secretion. We used isolated rabbit parietal cells prepared by collagenase digestion and counterflow elutriation. Acid secretion was assessed by the accumulation of 14C-aminopyrine within the cells. Two types of secretagogues were utilized: histamine (10(-6) mol/L), a membrane receptor agonist which acts by means of adenylate cyclase and cyclic AMP, and forskolin (10(-6) mol/L), a direct activator of adenylate cyclase. SRIF, SMS 201-995, and L-363,568 (10(-11) to 10( 7) mol/L) all significantly inhibited histamine-stimulated 14C-AP uptake (p less than 0.001). On a molar basis, SMS 201-995 was 10 times more potent and L-363,568 was 40 times more potent than SRIF. SRIF, SMS 201-995, and L-363,568 significantly inhibited forskolin-stimulated 14C-AP uptake (p less than 0.005). The inhibitory effects of SRIF and both analogues on forskolin-stimulated acid secretion was, however, significantly less than that observed with histamine (p less than 0.05). These results demonstrate increased in vitro potency of SRIF analogues compared with the native peptide. The data are consistent with the hypothesis that SRIF and its analogues function at more than one site within the parietal cell. PMID- 2891203 TI - Passage of somatostatin analogue across human and mouse skin. AB - Recent studies have documented beneficial effects of the somatostatin analogue, SMS 201-995 (hereafter referred to as SMS), when administered subcutaneously to patients with a variety of disorders. Since SMS is a small peptide, we tested the ability of two penetrant enhancers--dimethylsulfoxide and N-decylmethylsulfoxide (C10MS)--to promote transcutaneous passage of SMS. Samples of skin from human cadavers and hairless mice were tested in a static diffusion chamber. Application of SMS in conjunction with 1% C10MS resulted in rapid transdermal passage of SMS. These data were confirmed for hairless mouse skin in experiments with a modified diffusion chamber having continuous flow-through of receptor fluid in the subdermal reservoir. In this system, the cumulative amount of SMS that permeated hairless mouse skin was 20 micrograms/cm2/24 hours. Topical application of SMS with C10MS beneath a patch to mice confirmed in vitro data. Topical application of 10 micrograms of SMS resulted in plasma SMS levels of greater than 8,000 pg/ml within 2 hours. We conclude that SMS will cross both human and mouse skin, with a clinically significant flux, when administered topically with C10MS. The data support the feasibility of in vivo human trials of topical SMS therapy. PMID- 2891204 TI - Effect of somatostatin analogue (SMS 201-995) on molecular species of gastrin in gastrinoma. AB - Somatostatin analogue (SMS 201-995) has been shown to decrease total serum gastrin in patients with gastrinoma; however, the gastrin level rarely returns to normal, despite the near-complete inhibition of acid secretion. This implies that SMS may have an inhibitory action on the biologically active molecular species of gastrin and have little effect on biologically inactive species. To test this hypothesis, we determined the effect of SMS on the molecular species of gastrin in eight patients with the Zollinger-Ellison syndrome. Serum obtained before treatment and 6 hours and 18 hours after treatment (SMS 1 microgram/kg, subcutaneously) was sampled and assayed for molecular species of gastrin by means of gel filtration chromatography and fractional quantitation of gastrin species by radioimmunoassay. There was a significant decrease in the amount of G-34 and G 17 species. BBG and G-14 decreased, a change not significant at 6 hours but significant 18 hours after SMS. The distribution of the various molecular species as a percent of total immunoreactive gastrin was analyzed before and after SMS. There was a shift in the distribution of the molecular species, so that 6 hours after SMS treatment nearly 50% of total gastrin activity was accounted for by BBG and component I. SMS seems to have a different potency to inhibit release of the various gastrin molecular species. This observation may explain the failure of total gastrin levels to return to normal after SMS treatment in patients with the Zollinger-Ellison syndrome. PMID- 2891205 TI - [More candor in future national conferences]. PMID- 2891206 TI - [From clinical nursing: long-term tube feeding can cause deficiency diseases]. PMID- 2891207 TI - [Several features and mechanisms of lesions of the cardiovascular system in a severe course of hemorrhagic fever with renal syndrome]. AB - Peculiarities of lesions of the cardiovascular system were studied in 332 patients with a grave course of hemorrhagic fever with the renal syndrome. Deep cardiovascular disorders manifesting themselves in low or high arterial pressure, ECG changes, hemodynamic disorders in the greater and lesser circulation, disorder of the morphological structure of the myocardium and small vessel walls were revealed. PMID- 2891208 TI - [Beta blockade in acute myocardial infarction]. PMID- 2891209 TI - Toxic effects of mosquito coil (a mosquito repellent) smoke on rats. I. Properties of the mosquito coil and its smoke. AB - The physical and chemical properties of the mosquito coil, a commonly used mosquito repellent in Asia and South America, were analysed. The smoke emitted from the burning mosquito coil consists of submicron particles (diameter less than 1 micron) coated with a considerable amount of heavy metals, allethrin and a wide range of organic vapors, such as phenol and o-cresol. Therefore, a lengthy exposure to this smoke will cause adverse effects on the consumers. PMID- 2891210 TI - Toxic effects of mosquito coil (a mosquito repellent) smoke on rats. II. Morphological changes of the respiratory system. AB - A group of 20 female albino rats was exposed to mosquito coil smoke, 8 h a day, 6 days per week, for 60 days. An additional group receiving air exposure served as control. The smoke-exposed animals had a lower body weight than the controls. Smoke-induced histopathological lesions, including an inflammation of the tracheal epithelium, atelectasis of the lung parenchyma, emphysema, increase of alveolar macrophages in the alveolar space and perivascular infiltration of polymorphonuclear cells were observed in the experimental rats. An elevation of enzyme activities of lactate dehydrogenase, glutamate pyruvate transaminase, glutamate oxoacetate transaminase and acid phosphatase were found in the serum of the smoke-exposed rats indicating the enzymes were released from the damaged tissues into the blood stream. PMID- 2891211 TI - Effect of somatostatin analogue (SMS201-995) on cyclosporine levels. PMID- 2891212 TI - [Interhemisphere asymmetry of neuromediators in the brain of albino rats]. AB - The presence of interhemispherical asymmetry in the content of acetylcholine, norepinephrine, epinephrine, and dopamine is shown in experiments on albino rats. In this case no differences are observed in the acetylcholinesterase, monoamineoxidase and dopadecarboxylase activities in the left and right hemispheres. An assumption is advanced that neuromediatory interhemispherical asymmetry of the brain is connected with interhemispherical peculiarities of their storage, excretion and inverse capture. The data obtained should be taken into account in the study of pathogenesis of nervous-physical diseases and in the study of the mechanism of neurotropic drugs action. PMID- 2891213 TI - Sawfly poisoning in sheep and goats. AB - In September 1984 some sheep in a flock of 250 suffered depression, anorexia, incoordination and difficulty in rising; 50 ewes and weaners died. Post mortem examination revealed petechial bleeding, massive acute liver necrosis and in some animals degeneration of the kidney tubules. The rumen and gut contained many larvae of the blue-black birch sawfly (Arge pullata). Laboratory and field observations indicated that these were the cause of the illness. PMID- 2891214 TI - Protection of sheep against footrot with a recombinant DNA-based fimbrial vaccine. AB - Recombinant Pseudomonas aeruginosa cells containing the Bacteroides nodosus fimbrial subunit gene under the transcriptional control of a strong promoter produce large amounts of B. nodosus-type fimbriae. We have carried out vaccination trials which show that these fimbriae are just as effective as either natural fimbriae or whole cell preparations of B. nodosus in inducing protective immunity against homologous footrot challenge. The recombinant-produced fimbriae are also effective therapeutically in accelerating the rate of healing of pre existing footrot lesions. These results confirm that the structural subunit of the fimbrial strand is a primary protective antigen against footrot, and demonstrate the practicality and potential of recombinant DNA approaches to the development of new vaccines against B. nodosus and other Type 4 fimbriate pathogens. PMID- 2891215 TI - Early adrenal infection by herpes simplex virus type-1 (Miyama + GC strain): special reference to inoculation dose and spread from the adrenal to the central nervous system. AB - Male C3H/HeN mice, aged 5 weeks, were inoculated intraperitoneally (i.p.) with different doses (1 x 10(3), 1 x 10(5), 5 x 10(5), 1 x 10(6) pfu) of the herpes simplex virus type-1 (HSV-1) (Miyama + GC strain). The LD50 of this virus was 10(2) pfu (i.p.) per mouse. All the mice in each group died 12 days after inoculation. Adrenal necrosis was found to be dose-dependent, the threshold dose being 5 x 10(5) pfu. In addition, encephalitis and inflammatory cell infiltration in abdominal ganglia appeared in 3-4 days after inoculation. By the plaque method, HSV-1 was detected first in the adrenal glands, then in neurons in the spinal cord and the brain. These findings suggest that in mice inoculated with doses of virus sufficient to infect the adrenal gland, HSV-1 spreads to the central nervous system through peripheral nerves after replication in the adrenal. PMID- 2891216 TI - Establishment of a new human thyroid medullary carcinoma cell line. Morphological studies. AB - A new human medullary carcinoma cell line has been established from a thyroid tumor removed from a 76-year-old female patient. The cultured cells grew in suspension, formed round islands and did not attach to the plastic dish. The doubling time of 48 h is the shortest recorded for C-cell lines. Ultrastructural studies disclosed that the cells had a few short profiles of rough endoplasmic reticulum, numerous ribosomes and polyribosomes, a poorly developed Golgi apparatus and small secretory granules (75 nm in mean diameter). Immunohistochemical staining for somatostatin was positive. These results show that, compared with previously established C-cell lines, this cell line has a rapid growth rate, is morphologically less differentiated, but retains a hormone production potential. PMID- 2891217 TI - Mercuric chloride-induced nephrotoxicity in the rat following unilateral nephrectomy and compensatory renal growth. AB - The nephropathy induced by mercuric chloride was assessed in unilaterally nephrectomized (NPX) and sham-operated (SO) rats using histological and urinalysis techniques. This assessment was carried out in order to test whether or not rats are more susceptible to the nephrotoxic effects of mercuric chloride after unilateral nephrectomy and a period allowing for compensatory renal growth. Twelve days after surgery both NPX and SO rats were given a single 1.5, 2.0 or 2.5 mumol/kg dose of mercuric chloride (i.v.). Twenty-four hours after the 1.5 or 2.0 mumol/kg dose of mercuric chloride was administered, cellular and tubular necrosis in the pars recta segments of proximal tubules in the outer medulla was more severe in NPX rats than in SO rats. Moreover, the urinary excretion of a number of cellular enzymes (e.g. lactate dehydrogenase) and plasma solutes (e.g. albumin) was greater in NPX rats than in SO rats. At the 2.5 mumol/kg dose of mercuric chloride, renal tubular damage was quite extensive in both groups of rats; to such an extent that possible differences in renal tubular damage between the NPX and SO rats could not be determined histologically. However, the urinary excretion of alanine aminopeptidase was greater in the NPX rats than in the SO rats. Therefore, based on the aforementioned findings, rats that have undergone and adapted to a reduction in renal mass (i.e. unilateral nephrectomy) appear to be more vulnerable to the nephrotoxic effects of mercuric chloride than rats with two normal kidneys. PMID- 2891218 TI - Gap junction ultrastructure in rat liver parenchymal cells after in vivo ischemia. AB - The ultrastructure of gap junctions between rat liver parenchymal cells has been studied after in vivo ischemia, with and without subsequent blood reflow. Freeze fracture replicas were analysed by electron microscopic observation, optical diffraction and morphometric analysis. In control specimens gap junction connexons were widely dispersed and arranged in nearly random fashion over nearly the whole junctional area, with only minute spots of hexagonal connexon arrangement. An ischemic period of 30 min, from which the vast majority of cells are capable of recovery after restoration of the blood supply, usually entails only a slight enlargement of the areas of hexagonally arranged connexons. After 120 min of ischemia without reflow, which results in necrosis of most parenchymal cells, all gap junctions showed a completely hexagonal arrangement of connexons. The numerical density of connexons after 30 and 120 min of ischemia without reflow was significantly higher than in controls, whereas after 30 min of ischemia followed by 2 h of reflow the numerical density had returned to control levels. A fully hexagonal arrangement of gap junction connexons, as occurs after longer periods of ischemia, seems to be related to irreversible cell damage and presumably to metabolic uncoupling of cells. This was preceded by an increase in the numerical density of connexons, which is probably a reversible phenomenon. PMID- 2891219 TI - Necrotizing activity of tumor necrosis factor: histopathological investigation using Meth A sarcoma and granulation tissue. AB - The action of tumor necrosis factor (TNF) was investigated histopathologically in mice using methylcholanthrene A (Meth A)-induced sarcomas and granulation tissue induced by autotransplantation of fragments of liver and spleen. Highly purified murine TNF caused hemorrhagic necrosis of both the tumors and the granulation tissue. Proliferation of tumor capillaries, demonstrated microangiographically, occurred 2 h after TNF administration and hyperemia of tumor vessels was obvious after 3-6 h. Hyperemia and capillary leakage were also observed in the granulation tissue 6 h after TNF injection and hemorrhage was noted in the epidermis after 12 h. These results strongly suggest that the in vivo necrotizing action of TNF is mainly related to capillary injury. PMID- 2891220 TI - Immunohistochemical demonstration of decreased L-pyruvate kinase in enzyme altered rat liver lesions produced by different carcinogens. AB - Preneoplastic liver lesions were produced in female Wistar rats by application of 25 mg/kg N-nitrosomorpholine (NNM), 14 mg/kg diethylnitrosamine (DENA), 0.075 mg/kg aflatoxin B1 (AFB1) or 160 mg/kg safrole. These carcinogens were administered in two equal doses 12 and 24 h after partial hepatectomy. The animals then received sodium phenobarbital (0.1% in tap water) for up to 410 days. Numerous altered hepatic foci (AHF) and hyperplastic nodules (HN) were detected enzyme histochemically by their negative ATPase reaction after application of AFB1, DENA and NNM; some AHF and HN were also caused by the weak carcinogen safrole. Immunohistochemically these lesions were also L-pyruvate kinase (L-PK)-negative with a high coincidence with regard to their number and area. These results confirm the role of L-PK, an enzyme affecting the pentose phosphate pathway, as a negative marker of preneoplastic liver lesions. PMID- 2891221 TI - Rat renal carcinogenesis after chronic simultaneous exposure to lead acetate and N-nitrosodiethylamine. AB - Chronic oral administration of lead acetate and/or N-nitrosodiethylamine to rats produces three different types of renal cell tumors composed of basophilic, chromophobic or oncocytic cells. The most frequent tumor, often visible macroscopically, is made up of basophilic cells and forms tubular, cystic, pseudo papillary or solid structures; it may show considerable cellular atypia but does not metastasize or invade the surrounding parenchyma. Chromophobic and oncocytic tumors are rare and can only be detected with the microscope; they usually form cystic or solid structures. Basophilic and chromophobic tumors arise from specific segments of the proximal tubules, characteristic for each carcinogen: P2, P3C and P3M for lead acetate; P2 and P3C for N-nitrosodiethylamine. Karyomegalia in proximal tubule cells appears to be irrelevant in renal carcinogenesis. However, the appearance of basophilic and chromophobic cells in P2, P3C and P3M segments is considered to be an early change in tumor development. Oncocytic microadenomas originate from collecting ducts showing focal oncocytic transformation. Synergistic or inhibitory effects are not observed after chronic simultaneous administration of lead acetate and N nitrosodiethylamine, although both carcinogens act in common on P2 and P3C proximal tubule segments. PMID- 2891222 TI - [Detection of foci of hemorrhagic fever with renal syndrome in the Estonian SSR]. AB - Examination by the enzyme-immunoassay of organs of 10 small mammal species trapped in different landscape zones of the Estonian SSR revealed the presence of HFRS virus antigen in organs of bank voles and field mice. Radioimmunoassay studies of serum specimens from donors demonstrated the presence of antibody to HFRS virus in 2.54% of those examined. PMID- 2891225 TI - [Age specific frequency effects in a psychophysical reference system test]. PMID- 2891226 TI - [Schizophrenic thought disorders. Identification of parameters of reasoning processes for computer-assisted diagnostic findings in psychiatric diagnosis. II]. PMID- 2891224 TI - [Treatment of duodenal ulcer with famotidine]. AB - In a prospective double blind study the efficacy and safety of the new H2 receptor antagonist famotidine was compared with ranitidine. 48 patients with endoscopically proven duodenal ulcer were randomly allocated to receive famotidine 40 mg once at night, 20 mg bid, 40 mg bid or ranitidine 150 mg bid. After 4 weeks of treatment the ulcers of 7/12, 10/12, 9/12 and 6/12 patients were healed; the corresponding rates after 8 weeks were 9/12, 12/12, 11/12 and 10/12. Statistically there was no significant difference between the various groups. Adverse events of any clinical importance were not observed. These data indicate, that famotidine is as effective and as safe as ranitidine for the treatment of acute duodenal ulcer. PMID- 2891223 TI - Diabetes, dietary protein and glomerular hyperfiltration. AB - These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Drs Homer A. Boushey, Professor of Medicine, and David G. Warnock, Associate Professor of Medicine, under the direction of Dr Lloyd H. Smith, Jr, Professor of Medicine and Associate Dean in the School of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA 94143. PMID- 2891227 TI - [Dental injuries in children and adolescents--examination and diagnosis]. PMID- 2891228 TI - [Effect of the TRH analog DN-1417 on the appearance of frontal midline theta activity (Fm0)]. AB - The distinct 0 rhythm which appears in the frontal midline area during the performance of mental tasks is called Fm0. The appearance of Fm0 shows individual differences and a close relationship to the personality traits of the subject. It is also reported that administration of diazepam or alcohol brings about an increase of Fm0 along with lowering of the anxiety level. In the present study, the TRH analog DN-1417 (80 mg) was administered to 8 healthy male students for 15 days. They were all extrovert in nature and had no great neurotic tendencies as measured by the Maudsley Personality Inventory (MPI). EEG recording, determination of the blood concentration of DN-1417, and Spielberger's State Trait Anxiety Inventory-I (STAI-I) were carried out before, during, and after drug administration. The appearance of Fm0 showed significant increase during and just after drug administration. As to anxiety, the STAI-I score showed no significant change. There was no correlation between blood concentration and Fm0. From these results, we considered that the change of appearance of Fm0 due to drug administration was not necessarily associated with change of the anxiety level, and that DN-1417, a DA releaser, increased the appearance of Fm0. PMID- 2891229 TI - Identification in blood stains through DNA typing with C4 and HLA-DR probes. AB - A restriction fragment length polymorphism analysis using double digestion of DNA preparations with XbaI and BglII restriction enzymes and hybridization with C4 and HLA-DR probes is described. The typing conditions selected reveal extensive individual variation in both C4 and DR gene regions. In our panel of 46 unrelated individuals, 37 different phenotypic patterns were recognized when both probes were used, and preliminary discriminative power values of 0.865 and 0.914 were calculated for C4 and DR beta, respectively. The probability of a chance match using both systems is probably about 1.5.10(-2). The potential of this method for individual identification of blood stains was demonstrated on DNA prepared from 6 month-old dried blood stains from seven panel individuals. The seven individuals were all identified when comparing stain DNA patterns with panel control patterns. No RFLP pattern changes were observed following storage of blood stains. Based on these experiments with C4 and DR beta DNA typing under laboratory conditions, it is concluded that DNA typing with such probes may become a powerful tool in future stain identification analyses. PMID- 2891230 TI - [Clinical testis transplantation. Review of indications, surgical technic and results of auto-, allo- and isotransplantation]. AB - Human testicular transplantation using microsurgical technique is gaining popularity. Since 10 years autotransplantation of the testis proved to be a surgical technique with a definitive place in the therapy of high abdominal cryptorchidism. It is a procedure to be employed in situations where appropriate mobilisation yields an ineffective orchidopexy. In a review of 130 cases in the literature a success rate of 87% is reported. The problems of diagnostic procedures, of the indication and the possibilities of ischemia protection are described. Iso- and allotransplantation of the human testis are reported from few centers, but the results are excellent. Therefore, the operative technique and the long-term results are described in detail. PMID- 2891231 TI - [Use of the peroxidase method of immunoenzyme analysis for detecting Clostridium perfringens cells]. AB - The possibility of using the peroxidase method of the enzyme immunoassay for the detection of C. perfringens cells in the culture fluid of strains, as well as in affected tissues in cases of anaerobic gas gangrene infection, has been shown. This method is highly specific, convenient and takes but 1.5 hrs. PMID- 2891232 TI - [Possible serodiagnosis of pertussis infection by an immunoenzyme method]. AB - The sera of children and adults with a history of pertussis, as well as the sera of children immunized in three injections, have been studied in the enzyme immunoassay. The levels of antibodies to Bordetella pertussis protein and lipopolysaccharide, and to disintegrated B. pertussis cells have been determined; a serum titer of 1:1,600 and higher is considered as a criterion for the serological diagnosis of pertussis. PMID- 2891233 TI - [Use of specific Bordetella pertussis antibodies in immunoenzyme analysis for detecting the pertussis antigen]. AB - The competitive EIA technique with the use of peroxidase-labeled B. pertussis antigen has been developed. The data obtained in our investigations suggest the possibility of using this technique for the detection of B. pertussis antigen in faucial smears obtained from patients. PMID- 2891234 TI - [Disorders of the lower extremities in top marathon runners]. PMID- 2891235 TI - Insulin resistance following nocturnal hypoglycaemia in insulin-dependent diabetes mellitus. AB - Glucose metabolism was studied by a somatostatin-insulin-glucose infusion test (SIGIT) for 8 h in 7 male patients with insulin-dependent diabetes mellitus. They were investigated on two occasions in random order, with and without preceding hypoglycaemia induced between 3.00 and 4.00 h. SIGIT was started at 7.00 h when blood glucose was restored to normal and the counterregulatory hormones had returned to basal values. As expected, hypoglycaemia evoked an enhancement of the plasma levels of GH (43.7 +/- 10.1 vs 4.4 +/- 1.8 micrograms/l), cortisol (690 +/ 59 vs 140 +/- 32 nmol/l), glucagon (225 +/- 35 vs 143 +/- 25 ng/l), and epinephrine (3.80 +/- 1.00 vs 0.10 +/- 0.03 nmol/l). During the SIGIT, the levels of circulating free insulin and counterregulatory hormones were similar in the two tests notwithstanding that excessive hyperglycaemia appeared when SIGIT was preceded by hypoglycaemia. The present study thus demonstrates that nocturnal hypoglycaemia induces insulin resistance in insulin-dependent diabetic patients not deprived of insulin. PMID- 2891236 TI - Immunocytochemical localization of hFSH as an index of Sertoli cell function in the human testis. AB - The FSH receptor in the human testis has not been well characterized in vivo. Using an immunoperoxidase technique we have attempted the immunocytochemical localization of FSH in testicular tissue from patients with a variety of disorders including oligo- or azoospermia (N = 6), cryptorchidism (N = 3), and prostatic carcinoma (N = 3). Specific staining for hFSH was observed inside the seminiferous tubule, generally near the basal membrane in all except the cryptorchid patients. Specific staining was also localized in the luminal area of the seminiferous tubule. In most cases, FSH-positive cells were also found in the interstitium, with a minority of the cells being macrophages. The latter were more prevalent in the undescended testes and in orchiectomy specimens from patients with prostatic cancer. The pattern of FSH localization observed in this study probably represents receptorbound hormone, and may reflect damage to the Sertoli cell and its tight junctions. Further study of the changes in receptor distribution as an indication of Sertoli cell malfunction, may be helpful in our understanding of human testicular disorders. PMID- 2891237 TI - Use of Y-chromosome specific probe for detection of engraftment of bone marrow transplantation. PMID- 2891238 TI - Relationship between posttetanic count and response to carinal stimulation during vecuronium-induced neuromuscular blockade. AB - The correlation between degree of peripheral neuromuscular blockade and response to carinal stimulation was evaluated in two groups of 25 patients: one group was anaesthetized with thiopental, N2O and halothane, and the other group received thiopental, N2O and fentanyl. The degree of peripheral blockade was evaluated using train-of-four (TOF) and posttetanic twitch (PTC) stimulation of the ulnar nerve. The degree of diaphragmatic paralysis was evaluated indirectly by stimulating the carina and observing the corresponding muscular response, which was graded as severe, mild or absent. During halothane anaesthesia a PTC of 0 always indicated that no response to carinal stimulation could be elicited. On the appearance of the first response to posttetanic twitch stimulation (PTC = 1), 2% of the patients showed a mild response to carinal stimulation. At the first response to TOF stimulation, 48% of the patients reacted with a mild response. During thiopental, N2O, fentanyl anaesthesia one of 25 patients showed a mild response to carinal stimulation at a PTC of 0. When PTC was 1, 20% of the patients reacted mildly to the stimulation. At the first response to TOF stimulation, 92% showed a response to carinal stimulation; 24% of these responses were severe, necessitating intervention. It is concluded that the TOF response elicited peripherally is a late sign of neuromuscular recovery of the diaphragm, and that the method of counting posttetanic twitches is superior to the TOF response in evaluating early recovery of this muscle. Further, to ensure total diaphragmatic paralysis, the neuromuscular blockade of the peripheral muscles should be so intense that no response to posttetanic twitch stimulation (PTC = 0) can be elicited. PMID- 2891239 TI - A comparative microphotometric analysis of adult T-cell leukemia/lymphoma (ATLL) in the skin and mycosis fungoides (MF). AB - In the skin lesions of 16 adult T-cell leukemia/lymphoma (ATLL) and 13 mycosis fungoides (MF), morphological features of cutaneous infiltrates and their cell kinetics were evaluated through microphotometry of nuclear DNA content and nuclear size on Feulgen-stained sections. Lymphomas comprising some giant cells with irregular-shaped nuclei were found only in ATLL and these cells revealed aneuploid high DNA values. In contrast, neoplastic cells with pale cytoplasm in the Giemsa stain were seen more frequently in MF (69.5%) than in ATLL (12.5%). Patterns of the cutaneous infiltration according to skin microenvironments such as perivascular areas, dermal papillae, and periadnexal areas, were similar in the both entities. In the perivascular areas a mixed proliferation of lymphoma cells and non-neoplastic lymphocytes was conspicuous. The lymphoma cells were determined by high DNA values and large nuclear sizes. But the ratio of lymphoma cells to non-neoplastic cells in the infiltrates in the perivascular areas was higher in ATLL than in MF. In the dermal papillae and around the skin appendages, lymphoma cells predominated. Lymphoma cells which formed a plaque or tumor in the dermis contained many actively proliferating cells having higher DNA values and larger nuclear sizes than the lymphoma cells without tumor formation. One case of ATLL intermediate cell type showed, however, few proliferating cells inspite of tumor formation, suggesting a pooling or a long life-span in the skin. PMID- 2891240 TI - [Effects of tetrahydropalmatine and some other isoquinoline alkaloids on the uptake of [3H]dopamine into rat striatal synaptosomes and vesicular store]. PMID- 2891241 TI - [Role of protein kinases in the transmission of extracellular signals with special reference to the nervous system]. PMID- 2891242 TI - [Histamine in the central nervous system of mammals]. PMID- 2891243 TI - Murine Peyer's patches are capable of generating a cytotoxic T cell (CTL) response to nominal antigens. PMID- 2891244 TI - Characterization and mitogenic responsiveness of murine mammary gland mononuclear cells. PMID- 2891245 TI - [CT cisternography in the diagnosis of nasal cerebrospinal fluid fistulas]. AB - Four out of 12 patients with CT-cisternography were operated on. The CT findings were all confirmed at operation. In three patients with positive CT findings, the fistula was located at operation. In one case with negative CT findings, operation revealed no fistula either. Advantages of CT-cisternography are reliability of positive findings and the possibility of locating the fistula in some cases. The procedure bears relatively little risk and can be repeated. PMID- 2891246 TI - [Traumatic genesis of an aneurysm of the pericallosal artery]. AB - This is a report on a sac-shaped aneurysm of the pericallosal artery (that part of the anterior cerebral artery that follows the anterior communicating artery) also known as arteria pericallosa or pars postcommunicalis of the anterior cerebral artery. To exclude a fistula of the carotis cavernosus, angiography was performed that clearly showed an aneurysm of the pericallosal artery while there was no fistula of the carotis cavernosus. The vascular sac is considered to be due to trauma--this conclusion being arrived at on the basis of local conditions at the aneurysm and because of physical force having been exercised by a severe contusion of the cranium. The case was treated with success. It is discussed in this article with reference to relevant literature. PMID- 2891247 TI - [Etiology and therapeutic possibilities of post-traumatic erectile impotence]. AB - Based on 12 patients with posttraumatic erectile dysfunction due to pelvic fractures, ruptures of urethra and straddle-trauma, the diagnostic and therapeutic means in the management of erectile failure are discussed. The most frequent etiology encountered in posttraumatic erectile failure were combined arterial-neurogenic lesions followed by insufficiencies of the venae profundae penis as a sequelae of pelvic fractures or symphyseal ruptures. Promising therapeutic alternatives represent injections of cavernous bodies with vasoactive drugs, penile implants and also in suitable cases penile revascularization procedures. PMID- 2891248 TI - [Surgical therapy of dislocation fractures of the head of the humerus in adults. Personal procedure and results]. AB - Surgical intervention is indicated in the vast majority of humerus head fracture dislocations. In the present paper, we report on the results of 24 such interventions performed between 1975 and 1984. Implantation of a T-plate is considered the standard procedure to obtain osteosynthetic stability during exercise. However, in elderly patients or in cases of multiple fragment fracture, this procedure is inadequate to achieve the required stability. In such cases, development of a humerus head necrosis would rather be promoted. If a sufficiently stable osteosynthesis without the risk of necrosis cannot be achieved, we prefer replacement of the humerus head by a shoulder prosthesis to humerus head resection, resection-interposition-arthroplasty or shoulder arthrodesis. However, not only optimal surgical management of humerus head fracture dislocations has a decisive influence on the later function of the most flexible human joint with the important rotator cuff, but also properly performed active and systematic postoperative physiotherapy. PMID- 2891249 TI - [Involvement of the inner malleolus and deltoid ligament in supination trauma of the ankle joint]. AB - Additional ligament ruptures or fractures of the medial side of the ankle joint accompanying the lateral ligament rupture are rare. These injuries are more often in traumas with pronation-eversion movements of the foot. In cases of lateral ligaments ruptures we only found in 2.8% and in 5.9% additional medial injuries. This is confirmed by different biomechanical experiments. Experimentally the delta ligament rupture could mostly be caused by pronation-eversion movements or by forced plantar flexion of the foot. The diagnosis of bony lesions of the medial malleolus might be easy by X-ray, but ligament lesions of the medial ankle joint can be diagnosed easily too be using the stress X-ray controlling the medial talar tilt as a sign of medial instability. Because the necessity of surgical treatment is less important than of the lateral ligaments we recommend this procedure in cases of bilateral instability or if dislocation is obvious. PMID- 2891250 TI - [Traumatology of the alar ligaments]. AB - A postmortem study of craniocerebral traumas of varying severity was done to determine the pattern of injury of the alar ligaments. It was found that in the entire group of patients (n = 30) the alar ligaments were ruptured or suffused with blood 11 times. No close relationship was found between the massive nature of the cranial trauma and the severity of the injury of the alar ligaments. In some cases the alar ligaments were not at all involved even though the skull had suffered extensive osseous lesions, whereas on the other hand the ligaments were injured even though only soft parts had been involved (e.g., haematoma or dehiscent wounds of the scalp). Ruptures of the alar ligaments were typically involved in extended ruptures of the ligamentous apparatus (see Figure 6a involving the ligamentum apicis dentis, ligamentum transversum atlantis, m.atlanto-occipitalis anterior, m.tectoria, m.atlanto-axialis anterior et posterior). In some cases the pattern of injury of the alar ligaments was found to be decisive in enabling reconstruction of the course of the accident. Damage to the alar ligaments near the dens axis represent rotation injuries. On the other hand, insertion tears out of the condyli occipitales must be related to a lateral thrust tendency in indirect fracture of the skull (bursting fracture). Within this overall framework a new mechanism of fracture of the condylus occipitalis is described. As a matter of principle, the alar ligaments can become involved in consequence of rotation, traction and compression of the cranium. PMID- 2891251 TI - [The so-called accident neurosis--a controversial concept]. AB - After a short presentation of the legal bases concerning the field of legal accident insurance in the F.R.G., the development of psychic syndromes after accidents is described. The fact is stressed that such a development is always the result of a concurrence of several factors: the personality of the person involved, the accident itself--whereby one has to point out that not the event is decisive, but its result--, the relation between the medical physician and his patient, the fact of being insured against accidents, as well as further effects originating from the patient's environment. In the second part, the problem of judging the causal connection of the psychic symptomatology and the accident is discussed in detail. In this connection the terminological problems are investigated, too. It is underlined that the term "accident neurosis" does not fit at all, because it only seems to be classifying, but in fact different psychic developments demonstrated here in detail, are enclosed in this term. It is suggested to avoid that notion in future. Finally, the problem of granting a pension is discussed; also the question what kind of psychic consequences an actually given pension may bring, and finally the problem of treatment for these difficult patients. PMID- 2891252 TI - [An adolescent femoral neck dislocation fracture]. PMID- 2891253 TI - Genetic strategies for neuromuscular diseases. PMID- 2891254 TI - Constructing a complete restriction map of human chromosome 19. PMID- 2891255 TI - Molecular genetic strategies to investigate Huntington's disease. PMID- 2891256 TI - Attempts to identify the chromosomal localization of the Friedreich's ataxia locus. PMID- 2891257 TI - X-linked muscular dystrophies: studies through functional assay and DNA polymorphisms. PMID- 2891258 TI - Genetic and physical demarcation of the locus for dystrophia myotonica. PMID- 2891259 TI - Toward a molecular understanding of ornithine transcarbamylase deficiency. PMID- 2891260 TI - DMD carrier detection and prenatal diagnosis via recombinant DNA methods. PMID- 2891261 TI - Cellular and humoral mechanisms of cytotoxicity: structural and functional analogies. PMID- 2891263 TI - Taxol inhibits N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced human neutrophil polarization and H2O2 production while decreasing [3H]FMLP binding. AB - We have studied the effect of taxol on two N-formyl-methionyl-leucyl phenylalanine (FMLP)-induced neutrophil functions and the possible mechanism by which it inhibits these functions. Taxol inhibited FMLP-induced human neutrophil polarization (a characteristic change in neutrophil shape in response to a chemotactic stimulus) and H2O2 generation. Taxol also decreased the specific binding of [3H]FMLP to human neutrophils at 4 degrees C. The decreased binding of FMLP to its receptor may be responsible for the inhibition by taxol of FMLP induced polarization and H2O2 generation. PMID- 2891262 TI - Biology and genetics of hybrid resistance. PMID- 2891265 TI - A longitudinal study in a rural Tanzanian community 1982-1984. PMID- 2891264 TI - Histamine induced elevation of cyclic AMP phosphodiesterase activity in human monocytes. AB - We have previously reported histamine desensitization of human blood mononuclear leukocytes resulting in reduced cAMP responses to beta-adrenergic agonists, histamine and prostaglandin E1. This heterologous desensitization occurred at low, micromolar histamine concentrations and was accompanied by elevation of cAMP phosphodiesterase (PDE) activity in these cells. We have now investigated the activity of PDE in the lymphocyte and monocyte fractions of mononuclear leukocytes to determine the site of histamine effect. PDE activity per cell was higher in monocytes (0.075 +/- 0.070 units) than lymphocytes (0.026 +/- 0.08) units). Monocytes responded to 10(-6) M histamine stimulation with a much greater increase in PDE activity (0.354 +/- 0.1 units) than did lymphocytes (0.047 +/- 0.015 units). Histamine receptor studies, using thiazolylethylamine and chlorpheniramine as H1-agonist and antagonist respectively and dimaprit and cimetidine as H2-agonists and antagonists respectively, indicated that the histamine stimulation of PDE activity is mediated predominantly through H1 histamine receptor in the monocytes and the H1 receptor in the lymphocytes. Previously histamine had been thought to increase cyclic AMP by acting on H2 receptors to activate adenylate cyclase. Our studies show that stimulation of H1 or H2 receptors by low histamine concentration can cause the opposite effect i.e. increased catabolism and a net reduction in cAMP levels. The localization of this effect predominantly to monocytes indicates a potentially important mechanism for histamine action on immune regulation. PMID- 2891266 TI - Longitudinal study on the health status of children in Kikwawila village, Tanzania: study area and design. AB - The paper describes the study area and the project design of a longitudinal study on the health status of children undertaken in Kikwawila village in southeastern Tanzania from 1982 to 1984. This rural village is situated in the Kilombero river plain (270 m above sea level) and extends over 50 km2. A census in 1982 (repeated in 1984) revealed that 1152 (1406) people lived in 260 (299) households of the nucleated roadside settlements of the sectors Kikwawila and Kapolo. The vital statistics showed an infant mortality rate estimate of 198/1000 which was far above the regional (140%) and the national (137%) averages. Over 30 tribes were recorded but 6 tribes formed 84% of the population. The population was predominantly muslim (75%). Most adult inhabitants (90%) were subsistence farmers cultivating an average of 3.7 acres per household. Rice, maize and cassava were the main crops of the area. At the beginning of the study, the village had no village health post, dispensary or health centre and it lacked an adequate and safe water supply. A great proportion of the population (67%) had to rely on water from unprotected hand dug wells and from rivers for domestic purposes. Only half of the households had a simple pit latrine. Even when latrines were present, they collapsed after heavy rains due to loose, unconsolidated soils, termites and the high water table. These difficulties affected the sustained success of sanitation campaigns. The study area represented a typical settlement of the Kilombero valley and was, with regard to most demographic, ethnic, agricultural and health characteristics, considered a suitable pilot area. A primary health care programme based on village health workers was implemented in parallel with complementary community based studies on the causes, interrelations and control measures of the major health problems faced by the community, and possible control measures. PMID- 2891267 TI - Longitudinal study on the health status of children in a rural Tanzanian community: parasitoses and nutrition following control measures against intestinal parasites. AB - Three repeated cross-sectional surveys were undertaken among children (1 month to 15 years) of a rural community in southeastern Tanzania. The study was part of a longitudinal project on the interactions among nutrition, parasitic infections and immunity within a primary health care programme emphasizing village health workers. All children underwent interviews and parasitological, anthropometric, anamnestic and clinical examinations. Out of 550-590 children examined each year, a cohort of 170 children could be followed for three consecutive years. Malaria was holo- to hyperendemic in the community, P. falciparum accounting for greater than 90% of the infections. The parasite and spleen rates were 88% and 67%, respectively, and the average enlarged spleen index was 2.0 among children from 2 9 years in 1982. Transmission of malaria was high and stable as indicated by a parasite rate of 80% among infants between 1 month and 1 year during the whole period of study. G. lamblia, hookworm (N. americanus), Strongyloides spp. and Schistosoma haematobium were highly prevalent and annual incidence rates were high, while Entamoeba histolytica, Ascaris and Trichuris were of minor importance. Prevalence and incidence of parasitic infections did not differ by sex. Multiparasitism was very frequent and less than 11% of all children were parasite-free in each year. Not a single child remained parasite-free for three consecutive years. An anthropometric assessment showed a high degree of stunting (35-71%) and a substantial proportion of wasting (3-20%). The growth potential was normal in girls and boys during the whole period of study. There were indications that malaria was the main contributory factor to growth retardation among young children. Hookworm infection did not significantly affect the packed cell volume of the children, probably owing to the low intensity of infection. Due to the multiparasitism and the lack of parasite-free individuals, single parasite and single-nutrient effects were difficult to unravel. A latrine campaign followed by a single mass treatment against hookworm (single oral dose of albendazole, 400 mg) and/or G. lamblia (single oral dose of ornidazole, 40 mg/kg) only temporarily affected the prevalence and incidence of G. lamblia, and only resulted in a decrease in the intensity of hookworm infections up to six months after the interventions. As the effects of the latrine campaign and a single mass treatment on the parasite load were only transient, no sustained impact on nutritional variables was observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2891268 TI - Longitudinal study on the health status of children in a rural Tanzanian community: comparison of community-based clinical examinations, the diseases seen at village health posts and the perception of health problems by the population. AB - Standardised household interviews among adults and children, open-ended questionnaires, and clinical examinations administered during cross-sectional health status surveys, as well as the registers of village health posts (VHP), were used to assess the pattern of health problems of a rural community in southeastern Tanzania, and their results compared. All four approaches gave very similar results for the two major health problems (fever/malaria and abdominal pain or discomfort) which were mentioned by both children and adults. The parasitological data from the cross-sectional surveys also revealed hyperendemic P. falciparum malaria and a high prevalence and incidence for infections with hookworm (N. americanus), Strongyloides, and G. lamblia. However besides consistently revealing the two major health problems, each approach showed a distinct pattern for the additional health problems: household interviews and open-ended questionnaires resulted in a higher ranking of problems that had not yet been solved by the health care facilities available in the community at the time of the interview. This view was further biased by the fact that the interviews were done by people representing the health professionals. The statistics from the registers of VHP clearly reflected the types of treatment provided by this service. Malnutrition and various eye problems only became evident during the clinical examination of the population. However, the clinical examination did not identify the importance of the abdominal problems in the community. The cross-sectional survey (questionnaires, clinical examination) chiefly showed the health problems affecting the population around the time of the surveys (end of the dry season). Interestingly, the registers of the VHP did not show marked seasonal variations in the morbidity statistics for this community. Both questionnaire approaches and the registers of VHP showed a change in both the morbidity and the disease perception pattern that may reflect the effects of interventions launched at community level (activities of village health workers, mass-treatment against hookworm and G. lamblia). The study indicated that the individual ranking of the major health problems matched with data from health status surveys. It also pointed to the possibility that disease perception patterns could become a tool for community diagnosis and for the monitoring of health care programs. PMID- 2891269 TI - Serum proteins and zinc as parameters to monitor the health of children in a rural Tanzanian community. AB - Total protein concentration, zinc, prealbumin, albumin, alpha-1-, alpha-2-, beta- and gammaglobulin concentrations were measured in serum samples collected in three successive years (1982, 1983 and 1984) from children (1 month-15 years) of Kikwawila village, Tanzania. The analysis of a total of 1590 serum samples provided the baseline data for children living in a rural Tanzanian community. The total protein values and the concentrations of betaglobulin were within the range described for Caucasians. Albumin, prealbumin, alpha-1- and alpha-2 globulin concentrations were below these standard values. On the other hand the gammaglobulin concentration was twice as high. The concentrations of total protein, gammaglobulin and prealbumin correlated with age. From 1982 to 1983 a significant decrease of most of the serum components (incl. zinc) was observed, although in children older than 2 years the alpha-1-globulins increased. All values increased again from 1983 to 1984, except for the zinc concentration, which decreased further. The individual fluctuations were analysed by comparing paired values for the children participating in the period 1982-1983, or 1983 1984. The proportion of children showing large fluctuations, sometimes exceeding the selected limits of tolerance, was larger in the period 1982-1983 than 1983 1984. This was consistent with the overall pattern found for all children. The prealbumin level, which has been postulated to be an indicator for malnutrition or borderline malnutrition, was analysed in detail. The values were far below normal values (200-300 mg/l), reaching a plateau with 130 mg/l among 4-6-year-old children. The individual fluctuations indicated a decrease from 1982 to 1983, which was considerable both in terms of the proportion of children showing a decrease (55%) and in the magnitude of the decrease. There was an increase from 1983 to 1984 but this increase did not compensate for the loss in 1983. Prealbumin concentrations showed a slight trend towards decreased values with stunting and wasting. No direct correlation was found between the other biochemical parameters and the parasite or anthropometric data collected at the same time. It was difficult to establish direct relationships between the biochemical parameters, which mainly indicate the health status of the child at the time-point of the survey, and anthropometric parameters which reflect the history of the individual over a long period. No direct correlation could be established between the biochemical parameters and the parasitological data.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2891270 TI - A longitudinal study on relations of retinol with parasitic infections and the immune response in children of Kikwawila village, Tanzania. AB - From 1982 to 1984 170 children of Kikwawila village (Kilombero district, Tanzania) were followed for nutritional (anthropometric measures, hematocrit, serum retinol, prealbumin, and zinc concentrations), parasitological (malaria parasitemia, urinary schistosomiasis, intestinal parasites) and immunological characteristics. Between 2.9% and 12.4% had serum retinol levels less than 100 micrograms/l which indicate deficiency. Retinol concentrations were correlated with age, hematocrits, prealbumin levels and mid upperarm circumferences. The latter correlation may be useful in nutritional surveys and primary health care programs for the identification of populations at risk of retinol deficiency. No association was found between average retinol levels and the presence of parasites, with the exception of malaria. Retinol levels were inversely correlated with malaria parasitemia in 1982, and directly correlated with antibody titers to synthetic sporozoite peptide in 1984. Since retinol, malaria parasitemia, and antisporozoite antibodies increased with age, confounding by age could not be excluded. Six months after administration of ornidazole in a single oral dose of 10 mg/kg, a significant effect on the prevalence of Giardia lamblia was found. Following treatment, average retinol levels were increased in persons with confirmed G. lamblia infections, but not in uninfected or untreated controls. PMID- 2891271 TI - Food consumption patterns in a rural Tanzanian community (Kikwawila village, Kilombero District, Morogoro Region) during lean and post-harvest season. AB - A survey on food consumption was undertaken in 32 out of 260 households of a rural Tanzanian community (Kikwawila village, Morogoro Region) during the lean season (February) and the post-harvest season (August) in 1983. The survey revealed that the staples maize, rice and cassava are equally important food items of the diet during the lean season. In August, the post-harvest season, rice dominated the food pattern and often replaced the porridge made from maize or cassava. Green vegetables, especially cassava leaves, were the main relish dish for the majority of households in February. Fish became a daily item of the diet of most families in August. Concentrated energy sources such as fats, oil and sugar were scarce in both survey periods. The diets of all age groups of the population surveyed were highly deficient in energy (mean adequacy 58%) and protein (50%) in February. The FAO/WHO-recommended standards (Passmore et al., 1974) were met for protein in August but energy deficiency was still observed (mean adequacy 65%). The variations in energy intake were not only seasonal, but were also age and sex dependent. Young males (10 to 16 years) followed by the infants (6 months to 3 years) and old females (greater than 60 years) were the groups with lowest adequacy (less than 50%) in February. Males (10 to 60 years) had the greatest energy deficits in August. Iron requirements were generally met in most age groups during both seasons. However, children under 3 years as well as adolescent and adult females (mean adequacy 54-65% in August) were at risk for anaemia. The seasonal pattern of the diet did significantly influence the vitamin A intake. While the requirements were fully met in February, a deficiency was noted in August. The low adequacy (40%) for vitamin A during the post-harvest season could be related to the scarcity of leafy vegetables in the diets. The data are discussed and related to the health problems observed in the community during the post-harvest season for three consecutive years. PMID- 2891272 TI - Agricultural production in Kikwawila village, southeastern Tanzania. AB - Food production, land utilisation and agricultural structures were surveyed at Kikwawila village, north of Ifakara (Kilombero District, Morogoro Region) in 1984. This study was part of a more comprehensive, longitudinal programme to investigate the health status of a rural community, aiming in particular at the interrelations between nutrition, parasitic infections, immunity and the environment. Out of 340 households, 100 were interviewed and their subsistence farming activities recorded. The soil was found to be of great variability, being fertile where it was of alluvial origin but of reduced potential where it was non alluvial. In all, 70 plant species were registered as being cultivated, with rice, maize, cassava and beans providing the main staple food. Apart from a few exceptions, the fields were cultivated without any mechanization. The seasonal distribution of agricultural work is described, but no detailed workload analysis of the villagers with regard to age and sex has been performed. At the foot of the mountains, where artificial irrigation has been introduced, dry season cropping was practised in addition to the prevailing wet season farming, which rendered the cultivation of marketable crops (mainly tomatoes) possible. The farmers were found to be imaginative and capable of adapting to various conditions, irrespective of their tribal origins. Alternatively, the quality of the soil and the unreliable availability of water set limits to the potential of food production in the area. Although land is still available, it is becoming more scarce as the human population increases. The further impoverishment of the land represents an imminent danger. Therefore, top priority ought to be given to soil conservation, followed by intercropping and/or crop rotation, seed production and crop protection against game and pests. Means of implementing such measures are discussed. It is suggested that Community Agricultural Workers be installed, elected by the villagers and trained to establish the link between the existing agricultural extension service and the farmers' communities. PMID- 2891273 TI - Monitoring of community health status: experience from a case study in Tanzania. AB - The experience from the first four years of a longitudinal study on interrelations between nutrition, parasitic infections, immunity and environmental factors in a rural community, Kikwawila village (southeastern Tanzania) is reviewed. Two elements supported the implementation of the project. Firstly, the multidisciplinary approach with surveys across a range of biomedical and agricultural science disciplines has enabled the elucidation of part of the complexity of the mutually reinforcing, changing interrelations which can affect child health. Secondly, the primary health care component based on village health workers which paralleled the research project has facilitated the longitudinal character of the study and has triggered some community participation. The studies also indicated that the indigenous perceptions of disease, signs and symptoms may be used as an integrative tool to monitor health care programmes. Already during an initial stage of a project, the indigenous health perspectives could become indicators for community participation and could help to determine the strategy of applied research and control measures within primary health care. PMID- 2891274 TI - [N-acetyl-beta-D-glucosaminidase (NAG) activity in human semen: its relation to gamma-glutamyl transpeptidase (gamma-GTP) activity in seminal plasma and reproductive tissues, and relation between seminal mucoprotein concentration and seminal NAG, and gamma-GTP activities]. AB - N-Acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma GTP) activities in seminal plasma obtained from male infertile patients and these activities in reproductive tissues obtained from cryptorchids and patients with bladder tumors were studied. Seminal mucoprotein concentration was also measured. The mean NAG and gamma-GTP activity in seminal plasma was 2,092 +/- 794 mU/ml and 10,942 +/- 4,179 mIU/ml, respectively. The mean seminal mucoprotein concentration was 28.0 +/- 5.7 mg/ml. In seminal plasma, a significant correlation was obtained between NAG and gamma-GTP (p less than 0.001). and between gamma-GTP and mucoprotein concentration (p less than 0.05). However, there was no correlation between NAG and mucoprotein concentration. In the reproductive tissue high gamma GTP activity was observed in the testicular tissue and in the external gland of the prostate. The activity in the epididymis was higher in the tail than in the head. High NAG activity was observed in the epididymal head and in the internal gland of the prostate. In the testicular tissue, NAG activity was low. These findings showed that in the seminal plasma NAG and gamma-GTP activities were closely related but in the reproductive tissue, these activities located in different areas. PMID- 2891275 TI - Different electrophoretypes of human rotaviruses in Hungary. AB - Polyacrylamide gel electrophoresis of rotaviral double-stranded ribonucleic acid (RNA) extracted directly from faecal specimens collected in three different parts of Hungary was applied to characterize and distinguish 21 randomly selected viral isolates. This technique made it possible to define 7 different electrophoretypes. Of the isolates 11 exhibited an identical "long" electrophoretic migration pattern. "Short" RNA pattern was found in two cases, and one atypical rotavirus was also revealed. This is the first description of rotavirus RNA electrophoretypes in Hungary. PMID- 2891276 TI - Monoclonal antibodies to glycopolypeptides HA1 and HA2 of influenza virus haemagglutinin. AB - Anti-haemagglutinin monoclonal antibodies were prepared and their HA1 or HA2 specificity was determined by solid phase radioimmunoassay (RIA) using purified viral haemagglutinin (HA) and haemagglutinin glycopolypeptides HA1 and HA2, by radioimmunoprecipitation followed with SDS-PAGE, by immunoblotting and by inhibition of virus-induced haemagglutination. The capacity of these methods to estimate HA1 or HA2 specificity of anti-HA monoclonal antibodies (MoAb) was compared. HA1 specificity was demonstrated for all hybridomas originating from lymphocytes of mice immunized with complete influenza virus, except IIF4 hybridoma which was HA2-specific. All hybridomas obtained with lymphocytes from mice immunized with HA glycopolypeptide HA2 were HA2-specific. Anti-HA2 MoAb neither inhibit haemagglutination induced by the virus or by HA subunits nor neutralized viral infectivity, either alone or in mixture. As expected, all anti HA1 MoAb were H3 subtype-specific, showing usually good reactivity only with viruses close to the virus strain used for immunization. Two anti-HA1 MoAb (IVA1 and IVG6) showed unusual cross-reactivity within the H3 subtype. All anti-HA2 MoAb were broadly cross-reactive within the H3 subtype. Moreover, a half of them showed high cross-reactivity with influenza viruses of the H7 HA subtype. But the same antibodies did not react with HA of H1, H2 and H8 subtypes. PMID- 2891278 TI - Production of human influenza virus in a stabile line of guinea pig tongue cells expressing endogenous oncovirus: an electron microscopic study. AB - Guinea pig tongue (GPT) cells represent a highly sensitive host system for influenza A/WSN (H1N1) infection as evidenced by numerous ultrastructural changes, considerable production of NS1 protein and widespread budding of viral particles at the cytoplasmic membrane. Vesicles of smooth endoplasmic reticulum and of the Golgi complex were transported to the apical area of cell membrane, where the budding of virions took place. Numerous microtubules were directed vertically to these portions of plasma membrane. In contrast, maturation of the endogenous oncovirus particles occurred at the lateral cytoplasmic membrane. Beneath the area of oncovirus maturation and release, a network was seen of microfilaments oriented towards the plasma membrane. The cytoplasm of GPT cells contained numerous nonstructural protein inclusions, which evidently accumulated at the periphery of nucleoli and were seen to reach the cytoplasm crossing the pores of nuclear membrane. PMID- 2891277 TI - Studies on influenza-virus virulence in recombinants between epidemic and vaccine strains. AB - Influenza virus recombinants between epidemic strains A/Brazil/11/78 (H1N1), A/USSR/382/78 (H3N2) and vaccine strains A/Leningrad/9/46 (H1N1), A/Victoria/35/72/50 (H3N2) have been tested for virulence for humans and albino mice; their genome structure has also been determined. It has been shown that after the replacement of surface antigens of A/Leningrad/9/46 (H1N1) strain by surface antigens of A/Brazil/11/78 (H1N1) or A/USSR/382/78 (H3N2), strains, the virus becomes totally nonpathogenic for mice whereas its virulence for humans is enhanced. The combination in recombinant X/28 (H1N1) of haemagglutinin and neuraminidase of A/Brazil/11/78 (H1N1) virus and othercomponents of A/Leningrad/9/46 virus determines its high affinity to the epithelium of the upper respiratory tract of humans, as well as its marked virulence for seronegative volunteers. Genetic mechanisms of influenza virus virulence and the involvement of surface proteins in its specific manifestations are discussed. It has been shown that pathogenic properties and the affinity of the virus to particular tissues are determined by different genes and their reasortment can result in the appearance of essentially new properties in recombinants. PMID- 2891279 TI - Effect of human leukocyte interferon on HBsAg production in PLC/PRF/5 human hepatoma cell line. AB - We describe the effect of the natural human interferon alfa (HuIFN alfa) on HBsAg production in PLC/PRF/5 cells. Decreased HBsAg production was regularly demonstrated 48 hr after the treatment of cells with 3-300 IU of HuIFN alfa/ml; it lasted for further 24-48 hr depending from the amount of interferon (IFN) added. We found no differences in the sensitivity to HuIFN alfa of non-confluent cells as compared to cells which had reached confluency. The decrease of the extracellular HBsAg excretion seems to be due to inhibition of intracellular HBsAg formation. PMID- 2891280 TI - Rapid detection of respiratory syncytial virus in clinical specimens. AB - Results of the direct immunofluorescence (IF) test in 152 clinical specimens (throat swabs) were compared with those of respiratory syncytial virus (RSV) isolation. The prevalence of RSV infections in the upper and lower respiratory tract was high especially in infants until 12 months of age. The average RSV isolation rate was 18.42%, whereas the virus antigen detection was positive in 19.74% of cases. The agreement between virus isolation and direct IF was 92.1%, the sensitivity of IF being 82.14% and its specificity 94.35%. PMID- 2891281 TI - Studies on pathogenesis of fowl pox: virological study. AB - One-month-old WLH chickens were inoculated with a field isolate of fowl pox virus (FPV) by intradermal (i.d.) and intratracheal (i.t.) routes. In intradermally infected chickens, the virus in titrable amounts was first detected in the skin at the inoculation site on day 2 and in lungs on day 4 followed by viraemia on the day 5 post-infection (p.i.). Subsequently the virus was recovered from liver, spleen, kidney and brain, but not from the heart. The chickens infected by i.t. route showed an almost similar outcome with minor differences as the virus was first demonstrated in the lungs on day 2 p.i., viraemia occurred on day 4 p.i. Initiation of pocks at the inoculation site in i.d. infected birds was observed on days 3 to 4 p.i., generalized cutaneous pock lesions appeared from 7 to 8 days p.i. PMID- 2891282 TI - Evaluation of EIA kits for the detection of HIV antibodies. AB - We compared four commercially available enzyme immunoassay (EIA) kits for the detection of HIV antibodies using immunoblot analysis as a confirmatory test. The kits gave satisfactory results as far as sensitivity and specificity are concerned as required for the use in the laboratories of blood banks. For the sera of patients on haemodialysis, haemophiliacs, patients "under observation" for AIDS and homosexuals the results obtained by Behring and Organon kits were less satisfactory, as the number of false positive results was much higher than with kits produced by Genetic and Wellcome. The frequency of false negative results was small in the tests using Organon and Genetic kits, while using Behring and Wellcome kits no false negative results were found. PMID- 2891283 TI - Isolation of influenza A viruses from migratory waterfowls in San-in District, Western Japan, in the winter of 1982-1983. AB - From November 1982 to March 1983, winter migratory waterfowls of some species staying in San-in District, Western Japan, were surveyed for influenza virus at five stations. A total of eight influenza A viruses were isolated from 354 faeces samples of whistling swans; in contrast, no virus was isolated from any sample of 261 black-tailed gulls, of 113 pintails and of 10 mallards. Five of eight isolates belonged to human pandemic subtype H2N2, two isolates belonged to fowl plague subtype H7N7, and the remaining one to subtype H4N6. PMID- 2891284 TI - Herpes simplex virus antibodies in the cerebrospinal fluid of schizophrenic patients. AB - Antibodies to herpes simplex virus type 1 (HSV-1) were tested in the cerebrospinal fluid (CSF) of 262 schizophrenic patients by virus neutralization test (VNT) and enzyme-linked immunosorbent assay (ELISA). While VNT in the presence of complement revealed antibodies to HSV-1 in 18.3% of samples, ELISA was positive in 61.2% of cases; both tests were positive in 42 samples (16%). PMID- 2891285 TI - Contrast agent nephrotoxicity: comparison of ionic and nonionic contrast agents. AB - The effects on glomerular and proximal tubular function of an ionic contrast agent (sodium meglumine diatrizoate) and a nonionic agent (iopamidol) were compared in 34 patients with normal renal function. The patients received large doses (2.5 ml/kg body weight) of contrast material for IV digital subtraction angiography. Urine samples, collected before, immediately after, and on the first and third days after digital subtraction angiography, were analyzed for albumin, alanil-aminopeptidase, alpha-glucosidase, and beta-2-microglobulin. The changes noted were mild and of short duration with both contrast agents, despite the high dose given. These results suggest that, at least as far as renal toxicity is measured by these tests is concerned, ionic monomers can be safely used instead of more expensive nonionic media in procedures, such as digital subtraction angiography, that require high doses of contrast material. PMID- 2891286 TI - Low sensitivity of clinical MR imaging to small changes in the concentration of nonparamagnetic protein. AB - This study attempts to determine the magnitude of change in the concentration of a nonparamagnetic protein (human serum albumin) required to effect a detectable change in signal intensity on a clinical imaging unit. For a range of protein concentrations from 0-6100 mg/dl the concentration could not be predicted by inspecting the images. Measurement of displayed signal intensity failed to distinguish concentrations of 0.09-3700 mg/dl, while 6100 mg/dl gave slightly higher intensity signals. Although this low sensitivity represents expected behavior for low concentrations, the failure to differentiate the higher concentrations implies limitations imposed by clinical imaging techniques. Our results suggest that additional factors, such as paramagnetic material and motion as well as differences in protein concentration, may be involved in the MR signal intensities observed in pathologic CSF and cystic CNS collections. PMID- 2891287 TI - Anapsos, an antipsoriatic drug, in atopic dermatitis. AB - An open, controlled study was carried out in young patients with atopic dermatitis, who during one month received oral anti-psoriatic drug, anapsos (n = 46), or antihistamines (n = 30), simultaneously with topic applications. The activity and extension of the cutaneous lesions improved under both treatments, but more markedly with anapsos in spite of the fact that topical applications did not contain steroids in the group treated with anapsos, and the effect was still appreciable several months after interruption of medication. Anapsos, which was well tolerated, considerably relieved the respiratory symptoms of all patients with asthma. Studies performed on patients with atopic dermatitis have shown high IgE levels, eosinophils and T4 counts, and a marked decrease in T8 suppressor cells in peripheral blood. Our data also show a slight decrease in T8 cells (%), a significant increase in T4 sub-sets (%) and a high T4/T8 ratio as a previously reported by several authors. Such an imbalance between helper and suppresor cells may cause alterations in the response to extrinsic and intrinsic antigens, as shown in particular by the abnormally high IgE levels observed in atopic dermatitis. Anapsos was associated with a correction in T lymphocytes imbalances, specifically through the increase of the initially low T8 cells levels and subsequent normalization of the mean T4/T8 index. The tolerance and promising therapeutic activity of this antipsoriatic drug deserve further research in other conditions characterized by a deficit of suppressor cells. PMID- 2891288 TI - Complete evaluation of the cardiovascular lesions in 24 patients with Takayasu's aortitis using four-image, intravenous digital subtraction angiography. AB - We studied the entire distribution of cardiovascular lesions with the use of intravenous digital subtraction angiography (DSA) in 24 patients having Takayasu's aortitis. The aorta, its branches, pulmonary vessels, and left ventricle were assessed by neck (anteroposterior), abdominal (anteroposterior), and chest (right and left anterior oblique) images. DSA showed multiple arterial lesions (n = 24) including proximal renal artery stenoses (n = 4), pulmonary arterial stenoses (n = 4), inferior-superior mesenteric arterial anastomoses (n = 3), brachiocephalic arterial aneurysms (n = 2), aortic root aneurysm (n = 1), diffuse left ventricular hypokinesis (n = 1), subclavian steal phenomenon (n = 1), and right aortic arch (n = 1). The incidence of total occlusion was highest in the right subclavian artery (n = 12). Average percent luminal stenosis (mean +/- S.D.) over the aorta and its branches tended to be smaller in patients with prior corticosteroid therapy (17.3 +/- 14.6%) than in those without (22.0 +/- 9.8%), but the difference was not significant. DSA (four-series) was useful in assessing the whole disease spectrum and often revealed subclinical lesions in this disease. PMID- 2891289 TI - Use of nitrates in unstable angina pectoris. AB - The rationale for using intravenous nitrates in patients hospitalized with severe angina pectoris is that physiologic action is almost immediate. Many studies and clinical experience indicate that the use of this preparation results in a marked diminution of recurrent angina episodes in most patients. If adverse reactions such as severe hypotension or bradycardia occur, decreasing the dose or stopping it entirely corrects the problem. Intravenous nitroglycerin can be used in combination with other known antianginal agents, such as beta blockers and calcium antagonists. In clinical practice most patients are treated with nitrates and beta blockers or calcium antagonists because the combination of drugs may reduce ischemia and symptoms more than each drug used alone over a long period. PMID- 2891290 TI - Demographic considerations in the selection of antihypertensive therapy. AB - Because of the growing number of antihypertensive agents that are suitable for initial therapy in mild and moderate hypertension, it is important to identify factors that influence the response to various medications. Although individual patient considerations, such as associated illnesses and potential side effects, are of primary importance in choosing therapy, the influence of demographic factors has received increasing attention. The effect of age, race and gender on the response to antihypertensive therapy will be examined. Several studies have indicated that the beta blockers and angiotensin converting enzyme (ACE) inhibitors are more effective in younger than in older patients. Conversely, there is a trend toward greater responses in older subjects to the diuretics and calcium antagonists. In the few studies available that have compared agents in various classes, it appears that diuretics, and probably calcium antagonists, are significantly more effective than beta blockers or ACE inhibitors in patients over 60 years of age. However, the interdrug differences in young patients are probably less important. With regard to race, the relative lack of effect of beta blockers and ACE inhibitors in blacks is well accepted; in comparative studies, diuretics proved significantly better. From the few available studies, it does not appear that the calcium antagonists are more potent in either racial group, but they may be superior to the beta blockers and ACE inhibitors in blacks. Far less information is available concerning differences in antihypertensive responses between men and women. There is some suggestion that women may be less responsive to beta blockers than men.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891291 TI - Efficacy and safety of sustained-release diltiazem as replacement therapy for beta blockers and diuretics for stable angina pectoris and coexisting essential hypertension: a multicenter trial. AB - To determine if a sustained-release form of the calcium entry blocker diltiazem would be a satisfactory substitute for the combination of beta-adrenergic blocking agent and thiazide diuretic in the treatment of systemic hypertension and angina pectoris, 38 patients were studied in a 4-center trial. Blood pressure and heart rate were measured in the supine position, immediately after and 5 minutes after standing. Modified Bruce protocol treadmill tests were performed to determine the time to onset of 1 mm ST-segment depression, time to onset of chest pain and time to termination of exercise. Diltiazem monotherapy resulted in equivalent blood pressure control in 28 of 38 patients (74%). In the remaining patients, blood pressure control was achieved with resumption of the diuretic. Blood pressure with beta blocker plus diuretic compared with diltiazem were, in the supine position 137 +/- 22/82 +/- 7 (+/- 1 standard deviation) versus 139 +/- 22/82 +/- 8 mm Hg, immediately after standing 131 +/- 20/84 +/- 9 versus 133 +/- 21/82 +/- 10 mm Hg and after standing for 5 minutes 134 +/- 19/85 +/- 8 versus 137 +/- 18/85 +/- 9 mm Hg (difference not significant for each). The heart rate with diltiazem was higher supine (67 +/- 11 versus 60 +/- 11 beats/min), standing (73 +/- 13 versus 64 +/- 14 beats/min) and 5 minutes after standing (73 +/- 14 versus 63 +/- 14 beats/min, p less than 0.01 for each).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891292 TI - Autocrine-paracrine mechanisms of vascular myocytes in systemic hypertension. AB - Recent data demonstrate that in addition to its conduit function, the blood vessel is an active synthetic and secretory organ containing several autocrine and paracrine systems that are involved with the local regulation of its own function. The endothelium plays a pivotal role in modulating the balance between thrombogenesis and thrombolysis. In addition, it secretes vasorelaxant and vasoconstrictive substances, growth factors and inflammatory mediators that exert paracrine influences on vascular myocyte function. The vascular myocyte also expresses autocrine substances which influence its own function. The autocrine systems include angiotensin, prostaglandins, platelet-derived growth factor, insulin-like growth factor and heparin. These local factors exert modulatory influences on myocyte contractility and growth. It is conceivable that genetic or acquired abnormalities of one or several of these check and balance systems can result in increased vascular tone, generalized vascular hypertrophy or hyperplasia, or a combination, and contribute to the pathogenesis of hypertension. These autocrine-paracrine systems may be important targets for antihypertensive drug development. PMID- 2891293 TI - Prostatic carcinoma with endocrine features. A report of a neoplasm containing multiple immunoreactive hormonal substances. AB - A case of prostatic carcinoma with the cellular patterns of an adenocarcinoma and carcinoid tumor is reported. The tumor contained ultrastructural dense core neuroendocrine granules, and immunoperoxidase staining revealed prostatic acid phosphatase, prostatic-specific antigen, chromogranin, neuron-specific enolase, serotonin, adrenocorticotrophic hormone (ACTH), somatostatin, parathormone, calcitonin, bombesin, and glucagon but no insulin. The patient had exhibited hypercalcemia that may have been related to hormone production by the tumor. The literature on the endocrine aspect of the prostate and its tumor is reviewed. PMID- 2891294 TI - H2-receptor antagonists and duodenal ulcer recurrence: analysis of efficacy and commentary on safety, costs, and patient selection. AB - Maintenance treatment to prevent duodenal ulcer recurrence has been studied in more than 100 trials. These trials, together with reports of long-term safety of maintenance therapy, risk factors of ulcer recurrence, and economic implications of different strategies of long-term ulcer management have been analyzed. Recurrence rates with the FDA-approved drugs for maintenance therapy, cimetidine, ranitidine, and famotidine are comparable when compared as "weighted" or "unweighted" means. H2-blockers reduce the annual recurrence from nearly 70% to about 25%. The duration of maintenance treatment is uncertain, but probably should not be less than 1 yr. Cimetidine maintenance for up to 5 yr has not disclosed new side effects, and the rate of reactions decreases after the first yr. Maintenance is economically superior to intermittent treatment or surgery in the ulcer population, but long-term management should be individualized according to risk factors for recurrence. PMID- 2891295 TI - Antibody to hemorrhagic fever with renal syndrome viruses (Hantaviruses) in the United States. AB - Hantaviruses similar to those which cause hemorrhagic fever with renal syndrome have been isolated from rodents in the United States. Serologic evidence suggests that these viruses infect humans. Clinical disease has not, however, been associated with infection in the United States. To expand knowledge of the distribution of Hantaviruses in the United States and attempt to identify a clinical syndrome associated with infection, a serologic survey was undertaken of US Forestry Service personnel and US Geological Survey personnel in Mississippi, Virginia, and Alaska. In addition, sera from persons with unidentified illnesses were collected from state public health laboratories in Washington state and Virginia. One of 85 sera (1.2%) from Forestry Service personnel in Mississippi and one of 79 sera (1.3%) from Forestry Service personnel in Virginia, and nine of 360 sera (2.5%) from Forestry Service and Geological Service personnel in Alaska were tested by immunofluorescent assay and were found to have antibody to Hantaan, Tchoupitoulas, or Prospect Hill viruses, ranging in titer from 1:32 to 1:512. Those persons questioned revealed no renal disease, hemorrhagic phenomenon, or unidentified febrile illnesses. Sera from two persons in Virginia, collected at the time of an illness, had antibody titers of 1:32 and 1:64, respectively, to Prospect Hill virus. An etiologic role for Prospect Hill virus could not be confirmed. Current information would suggest that Hantaviruses do not present a public health problem in the United States. PMID- 2891296 TI - Dysfunctional alpha-globin genes in hemoglobin H disease in blacks: variation in restriction fragment size permits the detection of the -alpha/-alpha T genotype. AB - Hemoglobin H (HbH) disease is most often due to deletion of three of the four alpha-globin genes (genotype --/--alpha). In black subjects although the alpha/chromosome is common, the --/haplotype is very rare and few examples of HbH disease have been detected. We have studied three black siblings with HbH by restriction endonuclease mapping of the alpha-like gene complex (5'-zeta-psi zeta psi alpha 2-psi alpha 1-alpha 2-alpha 1-3') using zeta- and alpha- specific probes. The presence of size differences in the previously described hypervariable region between the zeta and psi zeta genes results in a restriction fragment length polymorphism which permitted the detection of single alpha genes on both number 16 chromosomes in these subjects. Quantitative DNA hybridization by a slot-blot technique confirmed that their genomes contained two alpha-globin genes. The results establish that in these black subjects HbH disease is associated with dysfunctional alpha-globin genes (genotype: -alpha/-alpha T). PMID- 2891297 TI - Exercise tolerance changes following renal transplantation. AB - Maximal exercise capacity was measured in 20 nondiabetic patients with end-stage renal disease before and soon after successful renal transplantation. Maximal oxygen consumption increased significantly in all patients posttransplant. Increases in maximal heart rate and heart rates at 70% of maximal levels were also observed. The changes in maximal oxygen consumption were not significantly correlated with changes in hematocrit. The removal of uremia may result in improved functioning of one or more of the systems involved in oxygen transport and utilization that determine exercise capacity. PMID- 2891298 TI - Globin gene-associated restriction-fragment-length polymorphisms in southern African peoples. AB - The combination of polymorphic restriction-enzyme sites in the 3' region of the beta-globin gene cluster shows very little variation in southern-African Bantu speaking black and Kalahari !Kung San populations. The sites of the 5' region, on the other hand, show marked variation, and two common haplotypes are present--the "Negro" type (- - - - +) and the "San" type (- + - - +)--in frequencies of .404 and .106, respectively, in the Bantu-speakers and .262 and .405, respectively, in the San. Twenty of 23 beta s-associated haplotypes in southern-African Bantu speaking black subjects were the same as that found commonly in the Central African Republic (CAR)--i.e., the "Bantu" type--a finding providing the first convincing biological evidence for the common ancestry of geographically widely separated speakers of languages belonging to the Bantu family. The (-alpha) haplotype has a frequency of .21 in the Venda, .07 in both the Sotho-Tswana and the Nguni, and .06 among the !Kung San. These data are interpreted in the light of Plasmodium falciparum malaria selection and population movements in the African subcontinent. PMID- 2891299 TI - Isolation and regional mapping of DNA sequences unique to human chromosome 21. AB - To isolate DNA sequences unique to chromosome 21 we have used a recombinant-DNA library, constructed from a mouse-human somatic-cell hybrid line containing chromosome 21 as the only human chromosome. Individual recombinant phage containing human DNA inserts were identified by their hybridization to total human DNA sequences and by their failure to hybridize to total mouse DNA sequences. A repeat-free human DNA fragment was then subcloned from each of 14 such recombinant phage. An independent somatic-cell hybrid was used to assign all 14 subcloned fragments to chromosome 21. Thirteen of the fragments have been regionally mapped using a somatic-cell hybrid containing a human 21 translocation chromosome. Two probes map proximal to the 21q21.2 translocation breakpoint, and 11 probes map distal to this breakpoint, placing them in the region 21q21.2 21q22. One of seven probes used to screen for restriction-fragment-length polymorphisms recognized polymorphic DNA fragments when hybridized to genomic DNA from unrelated individuals. These 14 unique probes provide useful tools for studying the structure and function of human chromosome 21 as well as for investigating the molecular biology of Down syndrome. PMID- 2891300 TI - Atopic dermatitis: the (wet) wrap-up. PMID- 2891301 TI - Periodic interactions of GH-releasing factor and somatostatin can augment GH release in vitro. AB - Growth hormone (GH) is secreted as pulses in vivo. To understand the signals governing this periodicity, we have established a perifusion-based model of pulsatile GH release. Male rat anterior pituitaries were dispersed and perifused with pulses of human growth hormone-releasing factor-(1--40) (GHRF), with or without a continuous or discontinuous somatostatin tonus. An experiment was composed of a 1-h base-line collection followed by four 3-h cycles; each contained single or paired 10-min infusion(s) of 3 nM GHRF. In testing the impact of somatostatin, the protocol was identical except that 0.3 nM somatostatin was added 30 min into the base-line period and then was either continued throughout the study or withdrawn during the periods of GHRF infusion. GH base lines with somatostatin were lower than vehicle base lines (P less than 0.05). GHRF pulses generated consistent peaks of GH release between 200 and 300 ng. min-1. (10(7) cells)-1, and these peaks were not altered by continuous somatostatin. In contrast, withdrawal of somatostatin during GHRF administration elicited markedly higher GH peaks (P less than 0.05) and more total GH release (P less than 0.05). This response could not be accounted for by the additive effects of GHRF and somatostatin withdrawal. PMID- 2891302 TI - Regulation of mitochondrial adenine nucleotide content in newborn rabbit liver. AB - This study examined the relationship between postnatal metabolic and hormonal changes and the accompanying rapid increase in mitochondrial adenine nucleotide content (ATP + ADP + AMP) in rabbit liver. The cytosolic NAD+/NADH concentration ratio, calculated from tissue pyruvate and lactate values, increased linearly 6.6 fold during the 1st postnatal h. The mitochondrial NAD+/NADH concentration ratio, calculated from tissue acetoacetate and beta-hydroxybutyrate values, increased 28 fold by 30 min postnatal. These changes in NAD+/NADH suggest that tissue oxygenation occurs rapidly and that oxygen supply rather than substrate supply is limiting for mitochondrial respiration in the immediate postnatal period. The normal increase in mitochondrial adenine nucleotide content that occurs within 2 h after birth was inhibited by hypoxia (5% O2). Glucagon stimulated the postnatal increase in mitochondrial adenine nucleotides but had no effect in combination with hypoxia. Both glucose and somatostatin injections inhibited the increase in mitochondrial adenine nucleotides and increased the insulin-to-glucagon ratio. Isoproterenol or dibutyryl cAMP stimulated, but propranolol did not inhibit, the normal increase in mitochondrial adenine nucleotide content. Phentolamine did not stimulate the postnatal accumulation of adenine nucleotides. In summary, the results show that the insulin-to-glucagon ratio is probably the most important hormone regulator of the rapid recompartmentation of adenine nucleotides into the mitochondrial matrix and that tissue oxygenation is strictly permissive for this hormone effect in the first 2 h after birth. PMID- 2891303 TI - Endogenous opioids may mediate secondary damage after experimental brain injury. AB - Although endogenous opioids have been implicated in the pathophysiology of spinal cord injury and brain ischemia, the role of specific opioid peptides and opiate receptors in the pathophysiology of traumatic brain injury remains unexplored. This study examined regional changes in brain opioid immunoreactivity and cerebral blood flow (CBF) after fluid-percussion brain injury in the cat and compared the effect of an opiate antagonist (Win 44,441-3 [Win-(-)]) with its dextroisomer Win 44,441-2 [Win-(+)] (which is inactive at opiate receptors) in the treatment of brain injury. Dynorphin A immunoreactivity (Dyn A-IR) but not leucine-enkephalin-like immunoreactivity accumulated in injury regions after traumatic injury; Dyn-IR increases also occurred predominantly in those areas showing significant decreases in regional CBF. Administration of Win-(-) but not Win-(+) or saline at 15 min after injury significantly improved mean arterial pressure, electroencephalographic amplitude, and regional CBF and reduced the severity and incidence of hemorrhage. Win-(-) also significantly improved survival after brain injury. Taken together, these findings suggest that dynorphin, through actions at opiate receptors, may contribute to the pathophysiology of secondary brain injury after head trauma and indicate that selective opiate-receptor antagonists may be useful in treatment of traumatic brain injury. PMID- 2891304 TI - Somatostatin inhibits cAMP-mediated cholinergic transmission in the myenteric plexus. AB - The mechanism by which somatostatin acts to modulate cholinergic transmission is not clear. In this study we investigated the role of the adenosine 3',5'-cyclic monophosphate (cAMP) system in mediating cholinergic transmission in the guinea pig myenteric plexus and examined the ability of somatostatin to alter acetylcholine (ACh) release stimulated by various cAMP agonists. Forskolin, 8 bromo-cAMP, vasoactive intestinal peptide (VIP), and cholera toxin each stimulated the release of [3H]ACh in a dose-related manner. Addition of theophylline enhanced the release of [3H]ACh stimulated by these cAMP agonists. In contrast 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, antagonized the action of forskolin, VIP, and cholera toxin but had no effect on that evoked by 8-bromo-cAMP. These observations suggest that cAMP may serve as a physiological mediator for ACh release from myenteric neurons. Somatostatin inhibited release of [3H]ACh evoked by various cAMP agonists in a dose-related manner. Maximal inhibition, observed in the presence of 10(-6) M somatostatin was 48 +/- 5, 47 +/- 9, and 43 +/- 12% of control for forskolin-, VIP-, and cholera toxin-evoked release of [3H]ACh. In contrast somatostatin at 10(-6) M inhibited only 20 +/- 5% of the release of [3H]ACh stimulated by 8-bromo-cAMP. Pretreatment with pertussis toxin antagonized the inhibitory effect of somatostatin on the release of [3H]ACh evoked by forskolin, VIP, or cholera toxin but had no effect on the inhibitory action of somatostatin on the release of [3H]ACh evoked by 8 bromo-cAMP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891305 TI - [3H]QNB binding and contraction of rabbit colonic smooth muscle cells. AB - We used radioligand binding and studies of cell contraction to characterize muscarinic receptors on dispersed smooth muscle cells from rabbit proximal and distal colon. Cells obtained after serial incubations in collagenase were used to measure binding of tritiated quinuclidinyl benzilate [( 3H]QNB). AT 37 degrees C, specific [3H]QNB binding was saturable and linearly related to cell number. Nonlinear regression analysis was used to determine the affinity of [3H]QNB for its receptor. In the distal colon the Kd was 60 pM, and the mean number of receptors was 1.2 X 10(6)/cell. Compared with cells from the distal colon, cells from the proximal colon had a lower affinity (Kd = 337 pM) but similar numbers of receptors. The concentrations of the antagonists atropine, secovorine, and pirenzepine, which were required for inhibition of 50% [3H]QNB binding (IC50), were 8, 5, and 870 nM, respectively, suggesting that the receptors are of the M2 muscarinic subclass. Hill coefficients for these agents were 1.1, 0.9, and 1.1, suggesting binding to a single receptor. The IC50 for the muscarinic agonists bethanechol and oxotremorine were 80 and 0.57 microM, respectively. Hill coefficients were 0.67 for both, suggesting more complex interactions involving receptors of different affinities. In studies of cell contraction, bethanechol stimulated a dose-dependent decrease in cell length with half the maximal contraction occurring at 100 pM. These results suggest that 1) contraction is mediated by binding of bethanechol to M2-muscarinic receptors and that 2) there are a large number of spare receptors in colonic smooth muscle. PMID- 2891306 TI - Neural, hemodynamic, and renal responses to stimulation of intestinal receptors. AB - Stimulation of visceral receptors with bradykinin has been shown to cause reflex increases in sympathetic nerve activity and systemic arterial pressure. In this investigation, serosal receptors of the intestine were stimulated by bradykinin in anesthetized cats to 1) compare mesenteric and renal sympathetic responses, 2) compare hemodynamic responses in mesenteric and renal beds, and 3) determine changes in renal function. This stimulation in intact animals caused pressor responses, significantly greater excitation of mesenteric than renal nerves, significantly greater mesenteric than renal vasoconstriction, diuresis, natriuresis, and, in denervated kidneys, increases in fractional sodium excretion. In vagotomized, sinoaortic-denervated cats, stimulation of intestinal receptors caused excitation of mesenteric nerve activity greater than renal for only 30 s. This sympathetic reflex response led to pressor responses, equal mesenteric and renal vasoconstriction, diuresis, natriuresis, and increased fractional excretion of sodium only in denervated kidneys. When abdominal perfusion pressure was held constant with an aortic snare in these same animals, the sympathetic reflexes initially caused greater mesenteric than renal vasoconstriction and antidiuresis and antinatriuresis only in innervated kidneys. These findings demonstrate that the intensity of hemodynamic and renal responses to stimulation of visceral receptors correlates well with the magnitude of sympathetic nerve responses. PMID- 2891307 TI - Accelerometric assessment of tardive dyskinesia. AB - Accelerometric measures associated with resting the hand, posturing the arm, and moving the arm were taken in 10 patients with tardive dyskinesia and eight schizophrenic patients matched for diagnosis, age, sex, likelihood of medication to induce extrapyramidal symptoms, and chlorpromazine-equivalent dose. A multivariate analysis of variance and follow-up univariate analyses revealed that the tardive dyskinesia patients showed 1) greater amplitude of dyskinetic movements, 2) lower peak frequency of dyskinetic movements, and 3) more spikes points beyond four standard deviations from the mean. Multiple discriminant analyses revealed that all patients were correctly classified as to presence or absence of tardive dyskinesia. PMID- 2891308 TI - Prospective seroepidemiology of hantaviruses and population dynamics of small mammal communities of Baltimore, Maryland. AB - We used a prospective seroepidemiological study, in conjunction with a mark release-recapture protocol, to investigate the transmission of hantaviruses in four rodent species from Baltimore, Maryland, from June 1984 to June 1986. A total of 1,208 captures of 762 rodents provided 984 individual blood samples. The antibody prevalence, as determined by frequency of reciprocal indirect fluorescent antibody (IFA) titers greater than or equal to 32, was 33.9% in rats (Rattus norvegicus, n = 466), 28.3% in meadow voles (Microtus pennsylvanicus, n = 67), 1.4% in house mice (Mus musculus, n = 146), and 1.2% in white-footed mice (Peromyscus leucopus, n = 83). Populations of all rodents were maximal during the fall and winter months, but population trends were not clearly associated with periods of virus transmission. The mean incidence of seroconversion to a Hantavirus for rats was 12.06/100 rats/month, but incidence rates could not be established for other species. Rats which seroconverted were generally sexually mature animals, and there was evidence of transmission throughout the year. Animals which seroconverted to a Hantavirus achieved high IFA titers, and remained seropositive for the duration of the study. PMID- 2891309 TI - Symposium: The epidemiology of mosquito-borne virus encephalitides in the United States, 1943-1987. In honor of William C. Reeves, Ph.D., M.P.H. Professor of Epidemiology. PMID- 2891310 TI - Professor William C. Reeves: scholar, teacher, and friend. PMID- 2891311 TI - Epidemiology and ecology of the California serogroup viruses. AB - The California serogroup viruses are important human pathogens, originally discovered in the United States, but now recognized to occur and cause disease in many parts of the world. In addition to their significance to public health, study of their natural history has resulted in a better understanding of the way in which arboviruses are maintained in nature. Viruses of the California serogroup have also been carefully investigated on the molecular level, resulting in a better appreciation of how viruses are constructed, organized, and replicate. William C. Reeves, in whose honor this symposium is held, has contributed throughout his career to each of these fields of endeavor. His pioneering work on these viruses, beginning with the discovery of the prototype California encephalitis virus, has helped to establish the foundations upon which our current understanding of these viruses is built. PMID- 2891312 TI - Overwintering mechanisms of mosquito-borne arboviruses in temperate climates. AB - It can be concluded from the data cited that transovarial transmission is a plausible explanation for the overwintering of mosquito-borne bunyaviruses of the California serogroup. Vertical transmission of mosquito-borne flaviviruses could explain the overwintering of this group of viruses, but this is far from having been established. At present, the mechanism by which mosquito-borne alphaviruses pass the winter is obscure. PMID- 2891313 TI - Strategies for surveillance, prevention, and control of arbovirus diseases in western North America. AB - Present strategies for surveillance, prevention, and control of arbovirus diseases in western North America have been developed from more than 4 decades of epidemiological research and development of mosquito control technology. Methods of prediction of outbreaks remain imprecise, although our understanding of sources of variation associated with indicators used for prediction is improving. Well organized and funded systematic mosquito abatement remains the most effective method of prevention of human cases of mosquito-borne virus disease, although emergency methods must be employed when outbreaks are imminent. The development of information management systems technology, use of recent developments of sampling theory, and research on vector competency and related areas should permit much better precision in estimates of impending outbreaks. PMID- 2891314 TI - Historical perspectives on the epidemiology and ecology of mosquito-borne virus encephalitides in the United States. PMID- 2891315 TI - The discovery decade of arbovirus research in western North America, 1940-1949. PMID- 2891316 TI - Topical levocabastine, a selective H1 antagonist, in seasonal allergic rhinoconjunctivitis. AB - Sixty-six patients with seasonal allergic rhinitis due to birch pollens, participated in an efficacy evaluation of topically applied, nasal and ocular, levocabastine, a highly selective H1 antagonist. A single blind comparison was performed between nasal levocabastine and flunisolide, a topical glucocorticoid preparation. Ocular levocabastine was compared with topical naphazoline/antazoline eye drops. Nasal and ocular symptom scores were recorded during a 31-day period. Pollen counts of birch pollens were done simultaneously. A global assessment of treatment efficacy was also made. In the comparison between the ocular treatments a significantly higher number of patients cited levocabastine excellent--it also had the advantage of fewer daily administrations. For nasal symptom scores the topical glucocorticosteroid therapy was in favour by number of sneezes. As for side effects, 44% of the patients complained of local irritation from naphazoline/antazoline eye drops or flunisolide nasal spray, but none with the levocabastine preparations. Topical levocabastine may provide an interesting alternative in the treatment of allergic rhinoconjunctivitis. PMID- 2891317 TI - Treatment of allergic rhinoconjunctivitis in Denmark. PMID- 2891318 TI - [Atracurium and vecuronium: interaction with three orally administered calcium antagonists in animal experiments]. AB - Interactions between calcium antagonists (CA) and muscle relaxants have been reported however due to the extremely high dosages of CA used in these studies, the clinical relevance of the observed interactions has been questioned. In order to simulate clinical practice--which entails long-term oral treatment and significant reductions in systolic blood pressure--CA were administered to rats orally (by gavage) for 8 days at a dosage that induced a systolic blood pressure decrease of not more than 25 +/- 5 mmHg. Ten groups of six male Sprague-Dawley rats each, body weight (BW) 313 +/- 23 g, were subjected to oral administration of three different CA: nitrendipine (1 mg/kg BW), nisoldipine (1 mg/kg BW), and diltiazem (100 mg/kg BW) or their solvents (control) three times daily by gavage for a period of 8 days. One hour after the last dose of drug or solvent, the rats were anesthetized (pentobarbital 60 mg/kg BW) and mechanically ventilated via tracheostomy. Monitoring included rectal temperature, carotid artery pressure, central venous pressure, heart rate, blood gases, and end-tidal CO2. Evoked train of-four (T4) twitch tension of the right tibialis anterior muscle was recorded continuously. After equilibration of vital signs and muscle twitch tension, vecuronium (150 micrograms/kg BW) or atracurium (500 micrograms/kg BW) was injected into the internal jugular vein four times at 5-min intervals after twitch tension had totally recovered and T4 fade had disappeared. Twitch depression, duration 90, and onset time of neuromuscular block in CA-pretreated animals were compared to control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891319 TI - Use of cyanuric chloride-activated paper for detection of subpicogram quantities of specific DNA sequences and its application to linked restriction fragment length polymorphism analysis in a Duchenne muscular dystrophy affected family. AB - Conditions for the optimal use of cyanuric chloride-activated (CCA) paper in Southern transfer hybridization experiments of genomic DNA were investigated. They depend critically on pH and ionic strength during transfer and on the composition of the hybridization solution. Simplified hybridization conditions using a SSC/dextran sulfate system at 65 degrees C without sodium dodecyl sulfate and the complex Denhardt's solution are applied. CCA paper allows repeated use in hybridization experiments. Under optimized conditions CCA paper allows a more sensitive detection of single-copy gene sequences in the subpicogram range than do nylon membranes. Application of these transfer and hybridization conditions with our newly developed CCA paper to carrier determination and prediction of the healthy male haplotype demonstrates its usefulness for prenatal counseling of a Duchenne muscular dystrophy family. PMID- 2891320 TI - Postnatal sequential development of dopaminergic and enkephalinergic perineuronal formations in the lateral septal nucleus of the rat correlated with local neuronal maturation. AB - Tyrosine-hydroxylase (TH-IR) and methionine-enkephalin like immunoreactivity (MetE-IR) were analyzed in the lateral septal nucleus (LSN) of the rat from birth (PO) to adulthood. TH-IR labeled specifically the dopaminergic (DA) pericellular arrangements of the LSN, as checked by negative dopamine-beta-hydroxylase and phenylethanolamine-N-methyl transferase-IR. TH-IR and Met-IR processes were present at birth in the medial LSN and extended lateralwards and caudalwards from P0 to P6 to constitute two main DA terminal fields (medial and lateral) surrounding a MetE one. Within these fields, the development of perineuronal baskets followed a similar medial to lateral sequence: DA axons first surrounded a few neuronal cell bodies at P3 in the medial part of the intermediate LSN; at P6, Met-IR axons encircled more laterally located perikarya, and only at P9, some neurons located along the ventricle in the lateral DA field became surrounded. The initial aspect of TH-IR baskets consisting of few axons surrounding the cell body rapidly evolved in a positive network encapsulating the perikaryon and long segments of the proximal dendrites, whereas MetE-IR varicosities remained restricted around the perikaryon and the initial dendritic segments. Ultrastructural study at P14 revealed numerous TH-IR and MetE-IR axosomatic and axodendritic profiles. TH-IR axosomatic varicosities exhibited asymmetrical synapses, whereas MetE-IR ones displayed rare symmetrical contacts. The medio lateral gradient of development of the perineuronal baskets was parallel to the postnatal neuronal development of the LSN as evaluated by cytological criteria: neuronal density, cell size and Nissl staining. Therefore, the formation of DA and MetE perineuronal arrangements in the LSN does not seem to be subordinate to the nature of the neurotransmitter they contain but related to the level of differentiation of their target neurons. A similar sequential set-up in the development of afferences paralleling the neuronal differentiation is discussed. PMID- 2891321 TI - Investigation of peripheral androgen resistance in genital hypoplasia associated with congenital growth hormone deficiency. AB - In a male infant with congenital growth hormone deficiency and genital hypoplasia (micropenis, cryptorchidism and small scrotum) androgen receptors, tissue specific 5 alpha reductase and steroid excretion pattern were determined in order to test the hypothesis of peripheral androgen resistance. A reduced number of cytosolic binding sites (Nmax) was found for the T and DHT receptor in patients foreskin compared to controls (n = 9) of similar age. The specific affinity (Kd) of the cytosolic receptor, however, was normal. Tissue specific 5 alpha reductase determination revealed a Vmax of 3.3 pmol/mg/h (controls 15.8 +/- 1.4). Analysis of urinary steroid excretion pattern revealed decreased levels of T metabolites, indicating impaired T metabolism. We postulate, that genital hypoplasia in patients with congenital GH deficiency is associated with impaired target organ responsiveness to androgen hormones caused by abnormalities within the pathway of intracellular reactions of T utilization. PMID- 2891322 TI - Evidence of sperm nuclear chromatin heterogeneity in ex-cryptorchid subjects. AB - Ex-cryptorchid subjects are frequently affected by infertility, even if the usually determined seminal parameters are still within the normal range. We evaluated in this study, in 14 ex-unilateral cryptorchid adult males (22-28 years), with normal sperm concentration, morphology and viability, the resistance of sperm nuclear chromatin to denaturation, using the fluorochrome acridine orange, which fluorescences green when bound to native DNA (double stranded) and red when bound to denaturated DNA (single stranded). Our findings demonstrate that the percentage of green-stained cells with acridine orange was significantly lower in our patients than in controls (p less than 0.001). We therefore suggest that the chromatin of ex-cryptorchid subjects' spermatozoa has a decreased resistance to denaturation and we hypothesize that this finding may explain the infertility of these patients, when the common seminal parameters are still within the normal range. PMID- 2891323 TI - Opioid analgesia at peripheral sites: a target for opioids released during stress and inflammation? AB - The peripheral analgesic effects of opiates were evaluated in a rat model of inflammation. The experimental design excluded a potential central nervous system site of action for the observed analgesia. After the injection of carrageenan (CARRA) in the plantar surface of both hind paws, an opiate was injected into one paw and saline was injected into the other paw. The inflamed paws injected with the mu-agonist, fentanyl (0.3 micrograms) or the kappa-agonist, ethylketocyclazocine (10 micrograms) were significantly less hyperalgesic (P less than 0.001 and P less than 0.01, respectively) than were the contralateral inflamed paws injected with saline. At these doses, fentanyl and ethylketocyclazocine were devoid of systemic effects. Another mu-agonist, levorphanol (20, 40, 80, or 160 micrograms) and dextrorphan (160 micrograms), its dextrorotatory isomer, were used next to evaluate opioid specificity. Levorphanol produced a dose-related blockade of CARRA-induced hyperalgesia (P less than 0.005). In contrast, 160 micrograms of dextrorphan was inactive. These results demonstrate that local administration of opiates into an inflamed paw produces a dose-related, stereospecific analgesia restricted to the injected area. PMID- 2891324 TI - The enflurane-sparing effect of alfentanil in dogs. AB - Some investigators believe that the dog is less sensitive than are humans to the anesthetic/analgesic actions of opioids. The alfentanil plasma concentration [ALF] vs anesthetic effect relationship has been determined for humans undergoing surgery. This study was designed to determine the [ALF] vs anesthetic relationship for alfentanil in the enflurane-anesthetized dog and thereby to provide data by which the [ALF] vs anesthetic effect relationships in the dog and in humans could be compared. Mongrel dogs (n = 10) were anesthetized with enflurane, and enflurane MAC (EMAC) was determined in each dog. After this, each dog received at least three incremental infusions of alfentanil using infusion rates of 0.625, 1.6, 8, 32, or 80 micrograms.kg-1.min-1. EMAC and [ALF] were determined during each infusion rate. There was a linear increase in [ALF] produced by incremental infusions of alfentanil (r = 0.999). Administration of alfentanil produced a dose-dependent reduction of EMAC up to a maximum of 72.5 +/ 3.7% (mean +/- SEM) at 32 micrograms.kg-1.min-1 ([ALF] = 960 +/- 86 ng/ml); a ceiling effect was evident. The degree of EMAC reduction (69%) produced by an infusion rate of 8 micrograms.kg-1.min-1 ([ALF] = 223 +/- 13 ng/ml) was not statistically different from the EMAC reductions produced by infusion rates of 32 (73% reduction at [ALF] = 960 +/- 86 ng/ml) or 80 micrograms.kg-1.min-1 (70% reduction at [ALF] = 2613 +/- 247 ng/ml) (P greater than 0.05). The relative potency of alfentanil was one-seventh to one-tenth that of fentanyl studied under identical conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891325 TI - Does diaphragmatic paralysis precede hand paralysis with vecuronium? PMID- 2891326 TI - Vecuronium and prolonged neuromuscular blockade in postpartum patients. PMID- 2891327 TI - Comparative pharmacokinetics of spinal opioids in humans: a step toward determination of relative safety. PMID- 2891328 TI - Pharmacokinetics of epidural morphine and meperidine in humans. AB - Five groups of surgical patients, each comprising six individuals, received epidural doses of morphine or meperidine, and the plasma and CSF kinetics were studied. Three groups received epidural doses of morphine 3 mg in 1 or 10 ml or meperidine 30 mg in 1 ml. Cerebrospinal fluid (CSF) and central venous blood opioid concentrations were measured intermittently for 6 h after injection. Two groups received epidural doses of morphine 3 mg in 1 ml or meperidine 30 mg in 1 ml, and opioid CSF concentrations were determined over a 24-h period. Morphine appeared rapidly in plasma, and maximum plasma concentrations were usually detected 5 min after injection and averaged 33 ng.ml-1 in the 1-ml volume group and 40 ng.ml-1 in the 10-ml volume group. The terminal plasma half-life averaged 91 +/- 34 min and 87 +/- 27 min, respectively (mean +/- SEM). Maximal plasma concentrations of meperidine were usually detected 10 or 15 min post-injection and averaged 196 +/- 29 ng.ml-1. The terminal plasma half-life averaged 124 +/- 26 min. Morphine crossed the dura relatively slowly, and the absorption half-life across the dura averaged 22 min. Maximal CSF concentrations were usually seen 60 90 min post-injection. In contrast, meperidine crossed the dura quickly, with an absorption half-life averaging 7.6 +/- 2.0 min. Maximal CSF concentrations were seen 15 or 30 min post-injection. Morphine and meperidine concentrations remained several times higher in the CSF than in the plasma. The fraction of the opioid dose crossing the dura was calculated to be 3.6% for morphine and 3.7% for meperidine. There were no significant differences in the kinetics of morphine administered in 1 or in 10 ml when CSF was sampled close to the site of lumbar epidural injection. The CSF concentration-time curves of both drugs decreased biexponentially after the initial rise due to diffusion across the dura. The early half-life in CSF averaged 73.3 +/- 11.5 min for morphine and 71.3 +/- 3.1 min for meperidine, and the late half-life averaged 369 +/- 113 min for morphine and 982 +/- 449 min for meperidine. Dose-normalized morphine and meperidine CSF concentrations after epidural administration showed that meperidine concentrations were down to one-fourth the corresponding morphine concentrations from the 2nd to the 15th h after administration, which may partly explain the longer duration of analgesia from morphine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2891329 TI - Pharmacokinetics of intrathecal morphine and meperidine in humans. AB - Two groups of surgical patients each comprising six individuals received an intrathecal injection of morphine 0.3 mg or meperidine 10 mg. Cerebrospinal fluid (CSF) and plasma were sampled frequently during a 6-h period and analyzed for morphine or meperidine. Maximum plasma morphine concentrations were found 5-10 min after injection, and averaged 4.5 +/- 1.1 ng.ml-1 (mean +/- SEM). Maximum CSF morphine concentrations were considerably higher than maximum plasma concentrations, 6410 +/- 1290 ng.ml-1. Maximum plasma concentrations of meperidine were also measured 5 or 10 min after injection and were low (36 +/- 9 ng.ml-1) compared with the maximum CSF concentrations (364 +/- 105 micrograms.ml 1). After a rapid initial decline for about 15 min after injection, the CSF concentrations decreased with a half-life of 89.8 +/- 16.1 min for morphine and 68.0 +/- 5.1 min for meperidine during the rest of the study period. The initial volume of distribution in CSF was similar for both drugs, or 22 +/- 8 ml for morphine and 18 +/- 5 ml for meperidine. After 6 h, 1.6 +/- 0.9% of the injected morphine dose and 0.41 +/- 0.09% of the meperidine dose remained in the initial volume of distribution. Large inter-individual differences in morphine and meperidine CSF kinetics existed, which may explain some of the reported individual differences in duration of effects. The disappearance of meperidine from CSF tended to be faster than that of morphine, which may be explained, in part, by the differences in lipid solubilities of the drugs. PMID- 2891330 TI - Drug actions at mammalian motor nerve endings: the suppression of neostigmine induced fasciculations by vecuronium and isoflurane. AB - The occurrence of fasciculations following administration of agents is a well known pharmacologic phenomenon. Using the cat soleus nerve-muscle preparation, intravenous neostigmine doses between 20-200 micrograms/kg evoked fasciculations in a dose-related manner. The data demonstrate that the fasciculations were the result of the direct effect of neostigmine acting at the motor nerve endings. Vecuronium in a dose-related manner (3 and 5 micrograms/kg iv) suppressed this prejunctional activity of neostigmine. The prejunctional effect of vecuronium explains its effectiveness in preventing succinylcholine-induced fasciculations. In the presence of isoflurane (end-tidal concentration 0.20-0.25%), the suppressant effect of vecuronium on motor nerve endings was enhanced. The prejunctional action of isoflurane may be a major contribution to the additive effects of non-depolarizing muscle relaxants and potent inhalation agents. PMID- 2891331 TI - Analgesia and ventilatory response to CO2 following epidural sufentanil in children. AB - The authors studied the effects of epidural sufentanil (0.75 microgram.kg-1) after urologic surgery in 15 children ranging in age from 4 to 12 yr, and in weight from 14 to 47 kg. The onset and duration of analgesia were 3.0 +/- 0.3 and 198 +/- 19 min, respectively (mean +/- SEM). Side effects included pruritus (3/15), nausea and vomiting (5/15), drowsiness (10/15), and urinary retention (1/11). No apnea was observed. Periosteal analgesia and ventilation were studied in eight of the children (mean age 8.6 +/- 0.8 yr). There was significant periosteal analgesia of the tibia (30, 60, 90, and 120 min after injection) and of the radius (60, 90, and 120 min after injection). Resting respiratory rate and tidal volume did not change during the study. Resting minute-ventilation decreased from 6.3 +/- 0.5 l.min-1 preoperatively to 5.6 +/- 0.6 l.min-1 (P less than 0.05) postoperatively, before epidural sufentanil injection; it did not decrease further after epidural sufentanil. Similarly, end-tidal CO2 tension increased significantly from 37.2 +/- 0.7 mmHg preoperatively to 39.9 +/- 1.2 mmHg (P less than 0.05) postoperatively, before epidural sufentanil; epidural sufentanil did not cause a further significant increase in end-tidal CO2 tension. The slope of the CO2 ventilatory response curve decreased significantly from 1.68 +/- 0.12 l.min-1. mmHg-1 preoperatively to 1.10 +/- 0.13 l.min-1.mmHg-1 (P less than 0.01) postoperatively. There were further significant decreases to 0.68 +/- 0.10 and 0.89 +/- 0.16 l.min-1.mmHg-1 30 and 60 min after epidural sufentanil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891332 TI - The effects of psychological desensitization on levels of patient comfort during oral surgical procedures. AB - The efficacy of psychological desensitization to reduce clinical pain associated with oral surgery was compared to diazepam plus meperidine I.V. Premedication. A visual analog scale was used to rate pain during local anesthesia administration and oral surgery. Psychological desensitization of patients who are to receive only local anesthesia during oral surgical procedures appears to be a significantly effective means of controlling patient pain perception. Such desensitization does not appear to be significant, however, in patients intravenous sedation. PMID- 2891333 TI - Five-year follow-up of a controlled trial of five 6-month regimens of chemotherapy for pulmonary tuberculosis. Hong Kong Chest Service/British Medical Research Council. AB - In a study in Hong Kong, Chinese patients with sputum-smear-positive pulmonary tuberculosis were allocated at random to five 6-month antituberculosis regimens. Four were pyrazinamide-containing regimens: 3 of these were given 3 times a week throughout, and contained isoniazid, rifampin, and pyrazinamide together with (1) streptomycin and ethambutol (HRZSE3), (2) streptomycin but no ethambutol (HRZS3), and (3) ethambutol but no streptomycin (HRZE3). The fourth contained the same drugs as Regimen 3, but was given daily throughout (HRZE7). The fifth regimen contained isoniazid, rifampin, streptomycin, and ethambutol, given 3 times a week, but no pyrazinamide (HRSE3). As previously reported, all 833 patients with drug-susceptible strains of tubercle bacilli pretreatment had a favorable bacteriologic response during chemotherapy, and bacteriologic relapse during the 2 yr (18 months after the end of chemotherapy) occurred in 9 (1.4%) of 626 patients in the pyrazinamide series (Regimens 1 to 4 combined) compared with 13 (7.8%) of 166 in the nonpyrazinamide series (Regimen 5) (p less than 0.001). The patients have been assessed at 4 and 5 yr after admission to the study. During the 5 yr, the total relapse rates for patients with drug-susceptible strains pretreatment were 3.4% for the pyrazinamide series compared with 10.3% for the nonpyrazinamide series (p less than 0.001). The results for the pyrazinamide series were also very good for the 104 assessable patients with strains resistant to isoniazid, streptomycin, or both drugs pretreatment: there was 1 failure during chemotherapy, 1 relapse during the first 2 yr and 2 subsequent relapses. PMID- 2891334 TI - Coexistence of multiple peptides and classic transmitters in airway neurons: functional and pathophysiologic aspects. PMID- 2891336 TI - [Neuroleptics: vigilance]. PMID- 2891335 TI - The electrophysiologic and neurochemical properties of paratracheal neurones in situ and in dissociated cell culture. AB - Although our knowledge of the intrinsic innervation of the airways is at present rather limited, it would appear that these neurones have several features in common with other intramural ganglia. They show a level of electrophysiologic diversity that might permit considerable integration and modulation to take place. Furthermore, the localization of a wide variety of neuropeptides in the neurones and in fibers within the paratracheal ganglia indicates that they may also possess the neurochemical specialization necessary to allow these ganglia to act as sites of complex local regulation. PMID- 2891337 TI - HLA-DQ restriction fragment length polymorphisms in myasthenia gravis. PMID- 2891338 TI - Immunogenetics of spontaneous, drug-induced, and experimental myasthenia gravis. PMID- 2891339 TI - 1986 Runme Shaw memorial lecture: The role of viruses & AIDS in cancer. PMID- 2891340 TI - Bronchodilators: beta 2 agonists versus theophylline. AB - Beta 2 agonists are best administered by inhalation since this route provides maximum therapeutic effect with minimum side effects. Plasma levels are lower and muscle cramps, tachycardia and tremor less common. Inhalation may be carried out by use pressurised inhalers (with various modification if necessary), by a Rotahaler with Salbutamol powder, and by nebulisers. All have their uses. Apart from their immediate bronchodilator effect, it is customary to give Beta 2 agonists routinely before inhalation beclomethasone, and there is evidence that regular use of Beta 1-agonists has a useful suppressive effect. In severe chronic asthma high doses may be indicated and be effective where conventional doses have failed. The introduction of reliable sustained-release preparation of theophylline and its derivatives together with plasma assays theophylline levels has enabled therapy to be optimal and side effects to be lessened. The therapeutic range is a plasma concentration of 10-20 mg/l. There are large individual variations in hepatic clearance of theophylline, which may also be influenced by age, liver disease, drugs and viral infections. Theophyllines are less effective as bronchodilators than Beta 2-agonists but in chronic severe asthma have a place for their additive effect. They are used most frequently to suppress nocturnal asthma and early morning wheezing. PMID- 2891341 TI - Treatment of intractable pain. AB - The mechanism of acute pain is believed to be mainly a neurophysiological event involving the transmission along A delta and fibers to the neuraxis and then via discrete paths to higher cortical levels. This incoming signal can undergo modification at a levels, either by other incoming signals, or by descending inhibition. In its refractory form chronic pain probably represents a complex balance of a nociceptive stimulus and its interaction with the co-existing psychological state, and behavioral factors. To successfully treat chronic pain it is necessary to direct therapy at the tissue damage (if any), the psychological state of the patient, and the environment in which the pain complaint is made, This often needs a multidisciplinary therapeutic environment to effect change. PMID- 2891342 TI - Back-up lights. PMID- 2891343 TI - [Bilateral Sertoli cell tumor]. PMID- 2891344 TI - The effectiveness of mosquito coils containing esbiothrin under laboratory and field conditions. AB - Tests were made to correlate the chemical content of mosquito coils with the knockdown and bite-inhibitory action of the smoke in the laboratory and with the protective effect in field use. Smoke from a blank coil, containing no pyrethroid, gave no knockdown, 10% inhibition of biting in the laboratory using Aedes aegypti, and 39% protection in field tests in village huts on the Kenyan coast with a mixed population of mosquitoes including 71% Anopheles gambiae. Coils containing low experimental contents of 0.044% and 0.099% Esbiothrin, an isomer blend rich in the D-allethrolone ester of D-trans-chrysanthemic acid, gave rapid knockdown in both small chamber and 25 m3 room tests, and 71% and 94% inhibition of biting respectively in the laboratory. In the field they gave 74% and 84% protection from mosquitoes alighting. Chemical content was therefore a good guide to knockdown and bite inhibition in the laboratory and also to the considerable protection found in the field. PMID- 2891345 TI - [A case of hemoglobin D Punjab in Tunisia. Characterization and structural study]. AB - Hb D Punjab is a hemoglobin abnormality due to the substitution of a glutamic acid by a glutamic on the hemoglobin beta chain: beta 121 Glu----Gln. Authors report here the first case of this rare variant in a tunisian family. PMID- 2891347 TI - [Inhibitory effect of alpha-2 adrenoceptor antagonist (DG-5128) on intractable asthma]. PMID- 2891346 TI - Multiplication and distribution of type 2 dengue and Japanese encephalitis viruses in Toxorhynchites splendens after intrathoracic inoculation. AB - The nonhematophagous mosquito Toxorhynchites (Tx.) splendens was found to be the most susceptible to type 2 dengue (D-2) and Japanese encephalitis (JEV) viruses among three hosts examined by virus titration and replication assays. After inoculation with D-2, the number of viral antigen positive cells in the head, thorax and abdomen increased up to day 15 and D-2 reached the maximum titer of 8.4 log10 PFU/g in the head on day 15. Hemocytes were the earliest cell type that could be detected as D-2 antigen positive on day 2. Multiplication of JEV was faster than that of D-2 in the mosquito. The number of JEV antigen positive cells in each part of the mosquito increased up to day 3, JEV reaching the maximum titer of 8.0 log10 PFU/g in the abdomen on day 3. Hemocytes and fat body cells (FBC) could be detected as JEV antigen positive cells on day 1. The time course of D-2 and JEV infection suggested that intrathoracically inoculated viruses were probably initially phagocytosed by hemocytes and/or FBC, and multiplied primarily in their cytoplasm. The infected hemocytes were then transported by the flow of body fluid and viruses were disseminated to other susceptible organs, such as ganglia, salivary glands, etc. The results obtained indicate that the course of infection of D-2 and JEV in Tx. splendens is similar to that in vector mosquitoes. Tx. splendens is therefore very useful for the study of these viruses. PMID- 2891348 TI - A histological study of the effects of different alpha-adrenergic and cholinergic agonists on the rat submandibular gland. AB - Rat submandibular glands were exposed to various sialagogues, including carbachol, clonidine, noradrenaline and cyclocytidine. The effects of these drugs were morphologically compared. Clonidine, which is an alpha-2-agonist, caused no depletion of granules in the serous cells examined. Noradrenaline and cyclocytidine, which are alpha-1-agonists, showed remarkable depletion of secretory granules in the serous cells. Carbachol caused visible and abundant salivation in the animals, but was found to produce only partial granular depletion of both serous and mucous cells. To induce experimentally a complete depletion of granular serous cells, cyclocytidine was found to be an excellent choice as a sialagogue with no side-effects on the cardiac and respiratory system. PMID- 2891349 TI - Detection of K88 and K99 fimbrial antigens on Escherichia coli by coagglutination. AB - Coagglutination was used to detect K88 and K99 fimbrial antigens on Escherichia coli, and results were compared to an enzyme immuno assay (EIA). When pili suspensions were tested by both methods, 28 of 66 cultures were shown to have K88 and 11 of 31 cultures had K99 antigens. No pili suspensions were positive by coagglutination that were not positive by EIA. Testing of cell suspensions gave equivalent results to pili suspensions for K99 when tested by coagglutination. Two cell suspensions reacted with the K88 coagglutination which could not be confirmed by testing of pili suspensions, while a further 20 out of 43 cultures gave equivalent results with both cell and pili suspensions for K88 when tested by coagglutination. PMID- 2891350 TI - Concordance and discordance of cognitive, behavioural and somatic self-ratings as a function of exposure: a Discan analysis. PMID- 2891351 TI - Hepatic glutamine metabolism. AB - The outstanding role of glutamine in hepatic nitrogen metabolism in general has been the subject of extensive research within the past few years. Hepatic glutaminase shows an extraordinary pH sensitivity, is not inhibited by glutamate and is activated by its product ammonium, thereby contrasting the kidney enzyme. In the absence of ammonium virtually no activity can be detected. Control of hepatic glutamine degradation is exerted at the level of glutaminase activity and glutamine transport across the plasma and mitochondrial membranes. These transport systems establish glutamine concentration gradients across the respective membranes: with a physiological extracellular glutamine concentration of 0.6 mM, the cytosolic and mitochondrial concentrations are 7 and 20 mM, respectively, both in vivo and in vitro. Therefore mitochondrial glutaminase is operating in vivo near its Km of 22-28 mM. In the intact liver acinus, glutaminase and the enzymes of the urea cycle are localized in the periportal hepatocytes, whereas glutamine synthetase is restricted to small hepatocyte population in the perivenous area; i.e., at the outflow of the sinusoid. Therefore, following the sinusoidal bloodstream, urea and glutamine synthesis are anatomically switched around. With respect to hepatic ammonium detoxication, this organization represents functionally the sequence of a periportal low-affinity system (urea synthesis) and a perivenous high-affinity system (glutamine synthesis) for ammonium removal. The role of glutamine synthetase is that of a scavenger for ammonium which has escaped periportal urea synthesis before the sinusoidal blood reaches the systemic circulation. The role of glutaminase is seen in a pH-modulated ammonium amplifier inside the mitochondria of the periportal compartment, thereby determining flux through the urea cycle. Periportal glutaminase and perivenous glutamine synthetase are simultaneously active, resulting in the so-called intercellular glutamine cycle. The role of this cycle is to improve the efficiency of hepatic urea synthesis at the physiologically low portal ammonium concentrations, thereby compensating the comparatively low ammonium affinity of carbamoylphosphate synthetase, the rate controlling enzyme of the urea cycle. Normally, periportal glutamine breakdown is matched by a compensatory perivenous glutamine resynthesis; thus no net glutamine turnover is observed. In addition, intercellular glutamine cycling is an effective means of adjusting flux of portal ammonium into either urea or glutamine according to the needs of systemic pH regulation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2891352 TI - Regulation of ciliary adenylate cyclase by Ca2+ in Paramecium. AB - In the ciliated protozoan Paramecium, Ca2+ and cyclic nucleotides are believed to act as second messengers in the regulation of the ciliary beat. Ciliary adenylate cyclase was activated 20-30-fold (half-maximal at 0.8 microM) and inhibited by higher concentrations (10-20 microM) of free Ca2+ ion. Ca2+ activation was the result of an increase in Vmax., not a change in Km for ATP. The activation by Ca2+ was seen only with Mg2+ATP as substrate; with Mn2+ATP the basal adenylate cyclase activity was 10-20-fold above that with Mg2+ATP, and there was no further activation by Ca2+. The stimulation by Ca2+ of the enzyme in cilia and ciliary membranes was blocked by the calmodulin antagonists calmidazolium (half inhibition at 5 microM), trifluoperazine (70 microM) and W-7 (50-100 microM). When ciliary membranes (which contained most of the ciliary adenylate cyclase) were prepared in the presence of Ca2+, their adenylate cyclase was insensitive to Ca2+ in the assay. However, the inclusion of EGTA in buffers used for fractionation of cilia resulted in full retention of Ca2+-sensitivity by the ciliary membrane adenylate cyclase. The membrane-active agent saponin specifically suppressed the Ca2+-dependent adenylate cyclase without inhibiting basal activity with Mg2+ATP or Mn2+ATP. The ciliary adenylate cyclase was shown to be distinct from the Ca2+-dependent guanylate cyclase; the two activities had different kinetic parameters and different responses to added calmodulin and calmodulin antagonists. Our results suggest that Ca2+ influx through the voltage sensitive Ca2+ channels in the ciliary membrane may influence intraciliary cyclic AMP concentrations by regulating adenylate cyclase. PMID- 2891354 TI - Inhibition of plant acetyl-coenzyme A carboxylase by the herbicides sethoxydim and haloxyfop. AB - Incorporation of [14C]acetate or [14C]pyruvate into fatty acids in isolated corn seedling chloroplasts was inhibited 90% or greater by 10 microM sethoxydim or 1 microM haloxyfop. At these concentrations, neither sethoxydim nor haloxyfop inhibited [14C]acetate incorporation into fatty acids in isolated pea chloroplasts. Sethoxydim (10 microM) and haloxyfop (1 microM) did not inhibit incorporation of [14C]malonyl-CoA into fatty acids in cell free extracts from corn tissue cultures. Acetyl coenzyme A carboxylase (EC 6.4.1.2) from corn seedling chloroplasts was inhibited by both sethoxydim and haloxyfop, with I50 values of 2.9 and 0.5 microM, respectively. This enzyme in pea was not inhibited by 10 microM sethoxydim or 1 microM haloxyfop. PMID- 2891355 TI - Revertant of the yeast Schizosaccharomyces pombe with modified alpha subunits of mitochondrial ATPase-ATPsynthase: impaired nucleotide interactions with soluble and membrane-bound enzyme. AB - A partial revertant from a mutant with modified alpha subunits of mitochondrial ATPase-ATPsynthase has been obtained for the first time from the yeast Schizosaccharomyces pombe. The purified F1 contains a lower amount of endogenous nucleotides as compared to the wild-strain enzyme. In contrast to the wild-type, the F1 ATPase activity from the revertant does not exhibit bicarbonate-sensitive negative cooperativity. The revertant Michaelis constant for Mg-ATP is very similar to that of normal F1 in the presence of bicarbonate while the Vm is slightly lower. The revertant enzyme is much less sensitive to inhibitions by ADP and by azide. It is proposed that the lack of negative cooperativity of revertant F1 ATPase activity is due to lower affinity for ADP, the release of which is no longer the rate-limiting step. PMID- 2891353 TI - Glycolipid anchors are attached to Thy-1 glycoprotein rapidly after translation. AB - The attachment of glycolipid anchors to the Thy-1 glycoprotein during biosynthesis was followed by the change of detergent-binding properties of biosynthetically labelled Thy-1 precursors upon phospholipase C treatment in the murine thymoma lines BW5147 and S1A. In S1A, 80% of the Thy-1 molecules were phospholipase-C-sensitive after a 2 min pulse with [35S]methionine, indicating that these molecules were already anchored via a glycolipid tail. In BW5147, 47% of the Thy-1 molecules had phospholipase-C-sensitive anchors attached after a 1.5 min labelling and, with longer pulses, this percentage rose to 76%. Tunicamycin did not block the addition of glycolipid anchors, and glycolipid attachment also occurred at 21 degrees C. The findings suggest that the attachment of glycolipid anchors occurs in the rough endoplasmic reticulum. PMID- 2891356 TI - Effect of spermine on tyrosine hydroxylase activity before and after phosphorylation by cyclic AMP-dependent protein kinase. AB - The effect of spermine on tyrosine hydroxylase (TH) activity purified from bovine adrenal medulla was examined before and after phosphorylation by the catalytic subunit of cyclic AMP-dependent protein kinase (A-kinase). Before phosphorylation, spermine (less than 1 mM) inhibited the enzymatic activity, and negative cooperative effect of spermine on TH (Hill coefficient = 0.7) was observed from the kinetic analysis concerning 6-methyl-5,6,7,8-tetrahydropterin (6MPH4). Spermine interacted noncompetitively toward tyrosine and the Ki for spermine was calculated to be 68 microM. Phosphorylation abolished the ability of spermine to inhibit TH activity in a negative cooperative manner against the pterin cofactor, and also increased four-fold the Ki value against the substrate. These results suggest that spermine may inhibit TH activity by interacting with the pterin binding site of the enzyme molecule in a manner of negative cooperativity, and that this inhibition is reversed by the conformational change of regulatory domain of TH after phosphorylation by A-kinase. PMID- 2891357 TI - Effects of alpha 2-adrenergic agonists on carbachol-stimulated catecholamine synthesis in cultured bovine adrenal medullary cells. AB - We examined the effects of alpha 2- and alpha 1-adrenergic agonists on synthesis of catecholamines in cultured bovine adrenal medullary cells. Clonidine, an alpha 2-adrenergic agonist, inhibited carbachol-stimulated synthesis of [14C]catecholamines from [14C]tyrosine in a concentration-dependent manner. Clonidine also inhibited carbachol-induced uptake of 45Ca2+ into cells at concentrations similar to those that inhibited the synthesis of [14C]catecholamines. Other alpha 2-adrenergic agonists, oxymetazoline and guanfacine, also strongly inhibited carbachol-stimulated synthesis of [14C]catecholamines. alpha 1-Adrenergic agonists, phenylephrine and norfenefrine, did not affect the synthesis. Tyrosine hydroxylase (EC 1.14.16.2) activity in a soluble fraction of cultured bovine adrenal medullary cells was assayed after gel filtration on a Sephadex G-25 column. Stimulation of the cells with carbachol increased the activity of tyrosine hydroxylase. Clonidine, oxymetazoline, and guanfacine all suppressed the carbachol-induced increase in activity of tyrosine hydroxylase in the cells. These results suggest that alpha 2-adrenergic agonists inhibit carbachol-stimulated synthesis of catecholamines by suppression of tyrosine hydroxylase activity, probably through the inhibition of Ca2+ uptake. However, the involvement of alpha 2-adrenoceptors in the inhibitory effects of alpha 2-agonists on catecholamine synthesis is still unsettled, since yohimbine failed to antagonize the inhibitory effect of clonidine on the synthesis in cultured bovine adrenal medullary cells. PMID- 2891359 TI - Depression of rat brain tryptophan hydroxylase activity following the acute administration of methylenedioxymethamphetamine. AB - The psychotomimetic agent, methylenedioxymethamphetamine, produced a rapid, persistent and dose-dependent reduction in cortical tryptophan hydroxylase activity when administered acutely to rats. This effect did not occur in vitro and did not require N-demethylase activity in the whole animal. Kinetic analysis revealed the loss of enzyme activity to be due to an alteration in Vmax with no change in the affinity of the enzyme for either its cofactor or substrate. Coadministration of the serotonin (5-HT) uptake inhibitor, citalopram, only partially antagonized the loss of tryptophan hydroxylase activity 3 hr after methylenedioxymethamphetamine, but completely prevented the loss of cortical 5 HT. Recovery of enzyme activity did occur by 1 week if the neurotoxic effect of methylenedioxymethamphetamine was blocked by fluoxetine. The effect of methylenedioxymethamphetamine on 5-HT synthesis was not affected by pretreatment with alpha-methyl-p-tyrosine, reserpine or yohimbine. Ketanserine and methiothepin, 5-HT receptor antagonists, did partially block the methylenedioxymethamphetamine-induced loss of tryptophan hydroxylase activity, suggesting a possible role for neurotransmitter release in the acute effects of the drug on enzyme activity. PMID- 2891358 TI - Characterization of histamine type 1 receptors on natural suppressor lymphoid cells. AB - Using the radioligand H1 antagonist [3H]pyrilamine, we have characterized the histamine type 1 receptor on cloned murine natural suppressor cells (NS). A single, specific binding site for [3H]pyrilamine exists on these cells. The binding was saturable and reversible by various specific H1 receptor antagonists. The rank order of potency for displacement of [3H]pyrilamine binding from the H1 receptor by H1 receptor antagonists was promethazine = pyrobutamine greater than pyrilamine greater than diphenhydramine greater than chlorpheniramine. The histamine type-2 agonists, impromidine and dimaprit, and antagonists, cimetidine and ranitidine, as well as selected non-histamine agonists, did not displace [3H]pyrilamine from its binding sites on the natural suppressor cells. The data indicate that the theoretical KD was 1.1 +/- 0.3 X 10(-7) M while the measured KD of binding for [3H]pyrilamine was 6.0 +/- 0.8 X 10(-8) M; the maximum binding was 4.13 nM and the number of binding sites/cell was 2.14 +/- 0.29 X 10(6) (N = 3). PMID- 2891360 TI - Changes in the enzyme activities involved in nitrogen assimilation in Mycobacterium smegmatis under various growth conditions. AB - Glutamate dehydrogenase (aminating) and glutamine synthetase activities were assayed in Mycobacterium smegmatis following growth on various carbon and nitrogen sources. The activities (expressed as nmoles product formed/min/mg crude extract protein) of these two enzymes were higher in crude extracts from glucose grown cells than in glycerol- or fructose-grown cells. In the presence of succinate, pyruvate, fumarate or acetate in the growth medium, both these enzyme activities were lower than those in citrate-grown cells. The glutamate dehydrogenase (GDH) activity was the same in asparagine and glutamine-grown cells. Ammonium chloride, alanine or glutamic acid, when used as nitrogen source, resulted in low GDH activity as compared to asparagine-grown cells. Glutamine synthetase activity was considerably lower (2-4 fold) when the cells were grown on alanine, glutamine, glutamic acid or ammonium chloride as the nitrogen source than those in asparagine-grown cells. Glutamate and ammonium chloride, when present in the growth medium, repressed both glutamate dehydrogenase and glutamine synthetase, though the degree of repression was small. The results suggest that only a weak transcriptional control operates for these enzyme activities in M. smegmatis. PMID- 2891361 TI - [A case of multiple subdural empyema complicated by intracranial mycotic aneurysm]. PMID- 2891362 TI - Generation of protein isoform diversity by alternative splicing: mechanistic and biological implications. PMID- 2891363 TI - Human tumor and immunodeficiency viruses. PMID- 2891364 TI - Does injection of non-depolarizing neuromuscular blockers before thiopentone affect their speed of onset? A study of tubocurarine and vecuronium. AB - In an open sequential pharmacodynamic study in 40 patients, the rate of onset of neuromuscular blockade using tubocurarine or vecuronium was measured. Comparison was made between groups of 10 patients who received thiopentone followed by either blocker and a "reverse" sequence where the blocker was injected before thiopentone. There was a small difference between groups, amounting to a few seconds in rate of onset of block, but this was not suggestive of a systematic effect of the drug sequence. PMID- 2891365 TI - Use of neostigmine in the antagonism of residual neuromuscular blockade produced by vecuronium. AB - Recovery from neuromuscular block produced by vecuronium was studied in 50 patients using electromyography and the train-of-four technique. Twenty patients received neostigmine 2.5 mg, 10 when the initial response of the train-of-four was 50% of control and 10 when it was 10%. Neostigmine 5 mg was investigated in a similar manner and in 10 patients spontaneous recovery was studied. In all patients the time to 70% recovery of the initial response and of the train-of four ratio was followed. Neostigmine significantly reduced the time to 70% recovery of both ratios with both degrees of block, but neostigmine 5.0 mg did not give a substantially more rapid recovery than 2.5 mg. No evidence of a neostigmine-induced block was encountered. neostigmine 2.5 mg was rapidly effective in antagonizing vecuronium-induced block, even when initial recovery was only slight: there was no advantage in using neostigmine 5.0 mg. PMID- 2891366 TI - Combination of fentanyl, etomidate and vecuronium may cause severe vagotonic state. PMID- 2891367 TI - The effect of nedocromil on weal reactions in human skin. AB - 1. Nedocromil 2% iontophoresed into human skin had no effect on wealing produced by intradermal histamine, 48/80 or house dust mite antigen. 2. Iontophoresis of 0.002-2% nedocromil itself resulted in dose-related wealing. 3. This wealing was reduced by 62 +/- 8% s.e. mean by the H1-receptor antagonist terfenadine which decreased histamine wealing by 68 +/- 2% s.e. mean. 4. Nedocromil may therefore act as a weak agonist on a skin mast cell receptor concerned with histamine release. PMID- 2891368 TI - Non-invasive instrumental techniques to detect terfenadine and temelastine induced suppression of histamine weals in man. AB - 1. The effectiveness of chronic dosing with temelastine (SK&F 93944) 75 mg twice daily and terfenadine 60 mg twice daily compared with placebo in inhibiting the weal and flare response to intradermal histamine was assessed using non-invasive objective assessment techniques. 2. The mean weal thickness, as measured by the A scan pulsed ultrasound device, was significantly decreased by both temelastine and terfenadine when compared with placebo. 3. There was a significant reduction in both the areas of the weal and the weal and flare, as measured by a digitizing tablet linked to a microcomputer, following treatment with temelastine and terfenadine compared with placebo and also between temelastine and terfenadine. 4. No significant difference was found in blood flow in the weal or flare as measured by the laser doppler flowmeter among any of the groups tested. 5. The ultrasound and digitizer techniques aid objectivity and precision in the investigation of the effects of drugs on histamine induced weals. 6. Temelastine and terfenadine were found to possess antihistaminic effects on histamine induced weal and flare in the skin. PMID- 2891369 TI - Sedative and cardiovascular effects of medetomidine, a novel selective alpha 2 adrenoceptor agonist, in healthy volunteers. AB - 1. Single intravenous doses (25, 50 and 100 micrograms) of medetomidine (MPV-785, an imidazole derivative), a selective alpha 2-adrenoceptor agonist, were administered to eight healthy male volunteers in a double-blind, placebo controlled study. 2. The following dose-related effects, all of which were compatible with an agonistic action of the drug at alpha 2-adrenoceptors, were noted: reductions of systolic and diastolic blood pressure (maximum 18/11 mm Hg), heart rate (maximum 10 beats min-1), saliva secretion (maximum 84%) and noradrenaline levels in plasma (maximum 70%). 3. Dose-dependent sedation or impairment of vigilance was also observed, both by subjective and objective (critical flicker fusion threshold) assessments, with the highest dose actually inducing sleep in five of the subjects. 4. The observed effects were in general agreement with those previously seen after intravenous administration of the centrally acting antihypertensive alpha 2-adrenoceptor activating drug, clonidine, but of a shorter duration. 5. The relative importance of alpha 2 adrenoceptors located in peripheral tissues and in the central nervous system for the drug's cardiovascular effects could not be determined, but the high lipid solubility of the compound and the rapid onset of sedation are in favour of a major central component. 6. Medetomidine may be a useful tool for the investigation of the physiology and pharmacology of alpha 2-adrenoceptors in man. In addition, the therapeutic and diagnostic uses of the compound should be investigated in pathological conditions related to increased sympathetic neuronal activity. PMID- 2891370 TI - Effects of antacids and food on absorption of famotidine. AB - The effect of a high potency antacid and food on the bioavailability of famotidine was studied in 17 healthy volunteers in an open randomized three-way cross-over trial. After an overnight fast, famotidine was administered to each subject as follows: 40 mg famotidine orally alone; 40 mg orally with antacid; and 40 mg orally with a standard breakfast. Coadministration of the antacid caused a small but significant reduction in the maximum plasma concentration (Cmax) of famotidine from 81.1 +/- 54.2 to 60.8 +/- 21.6 ng ml-1 (P less than 0.05) and a small decrease in the area under plasma concentration-time curve [AUC] from 443.3 +/- 249.2 to 355.0 +/- 125.1 ng ml-1 h (P greater than 0.05). However, there was only a minimal effect of food on these parameters; the Cmax and [AUC] were 81.6 +/- 29.6 ng ml-1 and 434.8 +/- 145.9 ng ml-1 h, respectively. PMID- 2891371 TI - Dual surface makers and HTLV-I proviral DNA in a cutaneous tumour nodule in a case of adult T cell leukaemia/lymphoma. AB - The phenotypic and morphological profiles of atypical cells in a case of adult T cell leukaemia/lymphoma were studied using a panel of monoclonal antibodies and electron microscopy. Retroviral sequence restriction analysis showed the presence of human T cell leukaemia/lymphoma virus type I (HTLV-I) in the skin lesion. Our case showed several unique features in the clinical, haematological, histopathological and immunohistochemical findings. An erythematous plaque and tumour nodules in the skin were found without any abnormal lymphocytes such as flower cells in the peripheral blood and bone marrow HTLV-I proviral DNA was detected in the skin tumour cells but not in the peripheral blood lymphocytes, and in the tumour nodule, atypical cells showed a distinct difference in morphology between cerebriform cells in the upper dermis and large lymphoid cells in the lower dermis. The cerebriform cells had, immunohistochemically, a T helper/inducer (Th/i) phenotype whereas the large lymphoblastoid cells possessed both the Th/i and T suppressor/cytotoxic (Ts/c) phenotypes. Ki-I antigen was detected in the large lymphoblastoid cells, but not in the cerebriform cells. PMID- 2891372 TI - Menstrual regulation by intramuscular injections of 16-phenoxy-tetranor PGE2 methyl sulfonylamide or vacuum aspiration. A randomized multicentre study. World Health Organization Task Force on Post-ovulatory Methods for Fertility Regulation. AB - A multicentre trial was conducted to compare the efficacy and side-effects of an intramuscularly administered PGE2 analogue and vacuum aspiration in women with a delay of up to 21 days in the expected onset of menses. A total of 473 such women were randomly allocated to treatment with either 16-phenoxy-W-17, 18, 19, 20 tetranor PGE2 methyl sulfonylamide (three intramuscular injections of 0.5 mg at 3 h intervals) or vacuum aspiration, and the outcome of therapy assessed 1, 2 and 6 8 weeks later. Retrospective analysis of hCG levels indicated that 419 (88.6%) women had been pregnant at the time of treatment. With few exceptions, administration of the PGE2 analogue induced vaginal bleeding in both pregnant and non-pregnant women but the duration and subjectively perceived amount of bleeding were greater than after vacuum aspiration. Both treatments were equally effective. In pregnant women the overall frequency of complete abortion was 91% for prostaglandin treatment and 94% for vacuum aspirations. If non-pregnant women were included, the respective success rates (i.e. percentages of women not pregnant 2 weeks after treatment) were 92% and 95%. Gastrointestinal side-effects and lower abdominal pain requiring intramuscular analgesia were more common after prostaglandin therapy than following vacuum aspiration in both pregnant and non pregnant women. PMID- 2891373 TI - Rotation of nucleotide sites is not required for the enzymatic activity of chloroplast coupling factor 1. AB - New heterobifunctional photoaffinity cross-linking reagents, 6-maleimido-N-(4 benzoylphenyl)hexanamide, 12-maleimido-N-(4-benzoylphenyl)dodecanamide, and 12 [14C]maleimido-N-(4-benzoylphenyl)dodecanamide, were synthesized to investigate the mechanism of ATP hydrolysis by chloroplast coupling factor 1. These reagents react with sulfhydryl groups on the gamma-polypeptide. Subsequent photolysis cross-links the gamma-polypeptide covalently to alpha- and beta-polypeptides. The cross-linkers prevent major movements of the gamma-polypeptide with respect to the alpha- and beta-polypeptides but are sufficiently long to permit some flexibility in the enzyme structure. When approximately 50% of the gamma polypeptide was cross-linked to alpha- and beta-polypeptides, a 7% loss in ATPase activity was observed for the longer cross-linker and a 12% loss for the shorter. These results indicate that large movements of alpha- and beta-polypeptides with respect to the gamma-polypeptide are not essential for catalysis. In particular, rotation of the polypeptide chains to create structurally equivalent sites during catalysis is not a required feature of the enzyme mechanism. PMID- 2891374 TI - Thermodynamics of active-site ligand binding to Escherichia coli glutamine synthetase. AB - Active-site ligand interactions with dodecameric glutamine synthetase from Escherichia coli have been studied by calorimetry and fluorometry using the nonhydrolyzable ATP analogue 5'-adenylyl imidodiphosphate (AMP-PNP), L-glutamate, L-Met-(S)-sulfoximine, and the transition-state analogue L-Met-(S)-sulfoximine phosphate. Measurements were made with the unadenylylated enzyme at pH 7.1 in the presence of 100 mM KCl and 1.0 mM MnCl2, under which conditions the two catalytically essential metal ion sites per subunit are occupied and the stoichiometry of active-site ligand binding is equal to 1.0 equiv/subunit. Thermodynamic linkage functions indicate that there is strong synergism between the binding of AMP-PNP and L-Met-(S)-sulfoximine (delta delta G' = -6.4 kJ/mol). In contrast, there is a small antagonistic effect between the binding of AMP-PNP and L-glutamate (delta delta G' = +1.4 kJ/mol). Proton effects were negligible (less than or equal to 0.2 equiv of H+ release or uptake/mol) for the different binding reactions. The binding of AMP-PNP (or ATP) to the enzyme is entropically controlled at 303 K with delta H = +5.4 kJ/mol and delta S = +150 J/(K.mol). At 303 K, the binding of L-glutamate (delta H = -22.2 kJ/mol) or L-Met-(S) sulfoximine [delta H = -45.6 kJ/mol with delta Cp approximately equal to -670 +/- 420 J/(K.mol)] to the AMP-PNP.Mn.enzyme complex is enthalpically controlled with opposing delta S values of -29 or -46 J/(K.mol), respectively. The overall enthalpy change is negative and the overall entropy change is positive for the simultaneous binding of AMP-PNP and L-glutamate or of AMP-PNP and L-Met-(S) sulfoximine to the enzyme. For the binding of the transition-state analogue L-Met (S)-sulfoximine phosphate (which inactivates the enzyme by blocking active sites), both enthalpic and entropic contributions also are favorable at 303 K [delta G' approximately equal to -109 and delta H = -54.8 kJ/mol of subunit and delta S approximately equal to +180 J/(K.mol)]. PMID- 2891375 TI - Site-directed mutants of staphylococcal nuclease. Detection and localization by 1H NMR spectroscopy of conformational changes accompanying substitutions for glutamic acid-43. AB - The high-resolution X-ray crystal structure of staphylococcal nuclease suggests that the gamma-carboxylate group of Glu-43 is directly involved in catalysis as a general base that facilitates the attack of water on the substrate phosphodiester. We have used primer-directed, site-specific mutagenesis to generate aspartate, glutamine, asparagine, alanine, and serine substitutions for this residue. The Vmax/Km for the aspartate mutant is reduced 1400-fold and the values for the charge-neutral mutations are reduced 5000-fold relative to the wild-type enzyme. Although these reductions in catalytic efficiency might appear useful in quantitatively estimating the importance of general basic catalysis in the reaction catalyzed by the wild-type enzyme, the thermal stabilities and 1H NMR spectral properties of the mutants suggest that such interpretations are ambiguous. All five mutants have higher melting temperatures for thermal denaturation than the wild-type enzyme, suggesting that the mutants have enhanced thermal stabilities relative to the wild-type enzyme. Chemical shift changes relative to the wild type are observed in both the aromatic and upfield-shifted methyl group regions of the 1H NMR spectra of the aspartate and serine mutants, suggesting the presence of conformational differences between the wild-type and mutant enzymes. That these conformational differences may be large enough to be mechanistically relevant is suggested by comparisons of the magnitudes of nuclear Overhauser effect (NOE) correlations between the aromatic and upfield-shifted methyl group regions observed via two-dimensional nuclear Overhauser effect correlation spectroscopy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891376 TI - The proton pore in the Escherichia coli F0F1-ATPase: a requirement for arginine at position 210 of the a-subunit. AB - Site-directed mutagenesis was used to generate three mutations in the uncB gene encoding the a-subunit of the F0 portion of the F0F1-ATPase of Escherichia coli. These mutations directed the substitution of Arg-210 by Gln, or of His-245 by Leu, or of both Lys-167 and Lys-169 by Gln. The mutations were incorporated into plasmids carrying all the structural genes encoding the F0F1-ATPase complex and these plasmids were used to transform strain AN727 (uncB402). Strains carrying either the Arg-210 or His-245 substitutions were unable to grow on succinate as sole carbon source and had uncoupled growth yields. The substitution of Lys-167 and Lys-169 by Gln resulted in a strain with growth characteristics indistinguishable from a normal strain. The properties of the membranes from the Arg-210 or His-245 mutants were essentially identical, both being proton impermeable and both having ATPase activities resistant to the inhibitor DCCD. Furthermore, in both mutants, the F1-ATPase activities were inhibited by about 50% when bound to the membranes. The membrane activities of the mutant with the double lysine change were the same as for a normal strain. The results are discussed in relation to a previously proposed model for the F0 (Cox, G.B., Fimmel, A.L., Gibson, F. and Hatch, L. (1986) Biochim. Biophys. Acta 849, 62-69). PMID- 2891377 TI - Distinct phases of the fluorescence response of the lipophilic probe N-phenyl-1 naphthylamine in intact cells and membrane vesicles of Escherichia coli. AB - The fluorescence of the lipophilic probe N-phenyl-1-naphthylamine (NPN) bound to intact cells of Escherichia coli is quenched by the addition of glucose, succinate, D-lactate, pyruvate, formate and glycerol. Partial recovery of fluorescence occurs on anaerobiosis. Use of mutants with defects in the ATP synthase or the respiratory chain show that quenching of fluorescence may be energized either by ATP hydrolysis or by substrate oxidation through the respiratory chain. Permeabilization of the outer membrane by treatment of intact cells with EDTA, or use of a mutant with an outer membrane permeable to lipophilic substances, results in a more rapid binding of NPN and in a decrease in quenching observed on substrate addition. NPN binds rapidly to everted membrane vesicles, but does not respond to membrane energization. It is proposed that inner membrane energization in intact cells alters the binding or environment of NPN in the outer membrane. The fluorescence recovery which occurs on anaerobiosis has two components. One component represents a reversal of the changes which occur on membrane energization. The other component of the fluorescence change is insensitive to the uncoupler CCCP and resembles the behaviour of NPN with everted membrane vesicles. It is suggested that a portion of the fluorescence events seen with NPN involves a response of the probe to changes in the inner membrane. PMID- 2891378 TI - 2-Keto-3-fluoroglutarate: a useful mechanistic probe of 2-keto-glutarate dependent enzyme systems. AB - 2-Keto-3-fluoroglutaric acid prepared by acid hydrolysis of its diethyl ester is stable, as the free acid in aqueous solution at pH 2, and can be stored at -20 degrees C for several years. Both enantiomers are reduced by NADH in the presence of glutamate dehydrogenase (EC 1.4.1.2) to the two diastereomers of 3-fluoro-L glutamate, which are stable at neutral pH and at high pH unless heated. 2-Keto-3 fluoroglutarate exists in solution almost entirely as a hydrate both at low and neutral pH. Both enantiomers of ketofluoroglutarate react with the pyridoxamine forms of aspartate, alanine and 4-aminobutyrate transaminases to give fluoride release. 2 mol of cosubstrate amino acid react for each mol of ketofluoroglutarate (KFG) when starting from the pyridoxamine form of the enzyme: 2 RCHNH2COOH + KFG + H2O----F- + NH4+ + glutamate + 2 RCOCOOH. Both diastereomers of fluoroglutamate are decarboxylated by glutamate decarboxylase (EC 4.1.1.15) with fluoride release: KFG + H2O----CO2 + F- + HCOCH2CH2COOH. By contrast, only one isomer of fluoroglutamate will react with the pyridoxal form of glutamate oxalacetate transaminase to give fluoride release: HOOCCHNH2CHFCH2COOH + H2O--- 4F- + NH4+ + HOOCCOCH2CH2COOH. The enzymatic decarboxylation of 3 fluoroisocitrate produces only one enantiomer of ketofluoroglutarate, which is reduced to threo (2R,3R)-3-fluoroglutamate by NADH and glutamate dehydrogenase: [2R,3S]-HOOCCH(OH)CF(COOH)CH2COOH + NADP+----[3R]-KFG + CO2 + NADPH + H+. The proton, 13C, and 19F-NMR parameters of ketofluoroglutarate and the two fluoroglutamate diastereomers are presented. These molecules are useful probes of enzymatic mechanisms thought to involve carbanion intermediates. PMID- 2891379 TI - F-244 specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A synthase. AB - A beta-lactone isolated from Scopulariopsis sp. shows a potent inhibition of cholesterogenesis. The structure of this beta-lactone, termed F-244, is 3,5,7 trimethyl-12-hydroxy-13-hydroxymethyl-2,4-tetradecadiendioic acid 12,14-lactone. The inhibition site of F-244 in cholesterol synthesis was studied. The growth of Vero cells was inhibited at 6.25-12.5 micrograms/ml of F-244. The inhibition of growth was overcome by the addition of mevalonate to the culture medium, but not by the addition of acetate. In a rat liver enzyme system, the incorporations of [14C]acetate and [14C]acetyl-CoA into digitonin-precipitable sterol were 50% inhibited by 0.58 microgram/ml of F-244. The incorporation of [14C]mevalonate was not affected. Studies on the effects of F-244 on the three enzymes involved in mevalonate biosynthesis demonstrated that the drug specifically inhibits HMG-CoA synthase with IC50 value of 0.065 microgram/ml. The effect of analogs of F-244 on HMG-CoA synthase was also investigated. PMID- 2891380 TI - Aggregation and thermo-inactivation of glutamine synthetase from an extreme thermophile, Bacillus caldolyticus. AB - The extreme thermophile, Bacillus caldolyticus, contains two regulatory isoforms of glutamine synthetase (glutamate-ammonia ligase, EC 6.3.1.2), E-I and E-II, produced as separate gene products. Light scattering and electron microscopy data indicate that these thermophilic enzymes aggregate to higher molecular weight species in two stages: initial polymerization of native dodecamers, followed by 'melting' of the aggregated species to produce amorphous denatured protein. The initial stages of the aggregation occurred at temperatures below those for time dependent denaturation, especially for E-II. In contrast, mesophilic (B. subtilis) enzyme showed no evidence of temperature-dependent aggregation. Thus, aggregation may be a stabilizing mechanism for the thermophilic systems. Bound metal ions and substrates caused dramatic increases in the temperatures at which aggregation and loss of activity occurred for thermophilic enzymes. Certain combinations of ligands (e.g., MnATP + L-glutamate) acted synergistically, so that these complexes denatured only above 90 degrees C. Various models were considered for heat-driven aggregation followed by denaturation, plus ligand stabilization. Taken together, the data are most consistent with unfolding of subunits within the dodecameric unit, rather than unfolding to monomers prior to aggregation. PMID- 2891381 TI - [Possible mechanism of ATP formation in energy-transforming biological membranes]. AB - An "elementary act" of ATP formation from ADP and Pi in energy-transducing organels (mitochondria, chloroplasts and chromatophores) can be realized without closed membrane vesicles, pieces of membranes and F0-component of H+ATPase. The "elementary act" is initiated by a rather fast deprotonation of several acid groups of the coupling factor F1 (or CF1), this process leads to structurally non equilibrium state of the enzyme due to the appearance of "additional" negative charges in unchanged protein globula. The endergonic step of ATP synthesis, i. e. release of tightly-bound ATP into the aqueous medium, occurs during conformational relaxation of the non-equilibrium state of H+ATPase. Closed membrane vesicles are necessary for a cyclic return of the enzyme to the initial state with protonized functional groups, this provides multiple synthesis of ATP under the steady state and quasi-stationary conditions. The energetical aspects and details of possible schemes of ATP synthesis initiated by artificial electrochemical gradient of protons, as well as ATP formation during oxidative and photophosphorylation are discussed here. PMID- 2891382 TI - Propranolol and somatostatin interactions with the hyperglycemic effects of glucagon, octopamine, noradrenaline and cAMP in worker honeybees in vivo. AB - The hyperglycemic effects of vertebrate glucagon, octopamine and noradrenaline, are depressed when propranolol or somatostatin is simultaneously injected into emerging adult worker bees. The inhibitory action of the peptidic antagonist (somatostatin) is more marked against the peptidic agonist (glucagon) and the action of the aminergic antagonist (propranolol) is more marked against the aminergic agonist (octopamine). Somatostatin seems to be inactive against the hyperglycemic effects of cyclic AMP itself. Lastly, octopamine and cAMP might share a common stimulatory activity towards the honeybee's hemolymph trehalases. PMID- 2891383 TI - Amitriptyline in the treatment of neuroleptic-induced akathisia. PMID- 2891384 TI - Neuroleptic-induced akathisia: propranolol versus benztropine. PMID- 2891385 TI - Identification of the specific proteins associated with differentiation of spermatogonia in mice by two-dimensional gel electrophoresis. AB - Protein synthesis in testicular germ cells was studied during the differentiation of Type A spermatogonia in testes from adult cryptorchid mice to Intermediate and Type B spermatogonia in organ culture by two-dimensional gel electrophoresis. By comparing the patterns of Type A spermatogonia with those of differentiated (Intermediate and Type B) spermatogonia, we found two newly synthesized protein spots that correlated with differentiation. The isoelectric points (pIs) and molecular weights (MWs) of these proteins were estimated to be approximately pI 5.4, MW 67,000, and pI 5.8, MW 28,000, respectively. PMID- 2891386 TI - Fractional exponential decay of a membrane protein population due to capture by coated pits. AB - We consider the lateral diffusion of receptors, or other membrane proteins, in the outer membranes of certain cells, and their capture by coated pits. It is shown, for the case in which the coated pits are in fixed random positions, that the long-time decay of the total number of uncaptured proteins is of the fractional exponential form, N(t) = N0 exp [-square root of (t/tau)], and not of the pure exponential form, N(t) = N0 exp(-t/tau), which is usually assumed. PMID- 2891387 TI - Genotypes of thalassemia major and intermedia in Italy. PMID- 2891388 TI - Expression of TGF-beta gene in adult T cell leukemia. AB - Peripheral mononuclear cells from adult T cell leukemia (ATL) patients were analyzed in comparison with other types of leukemia cells, for the expression of transforming growth factor-beta (TGF-beta) mRNA, for the presence of TGF-beta activity (colony stimulating activity for normal rat kidney fibroblasts [NRK]) in conditioned medium and for their susceptibility to exogenous TGF-beta. Highly elevated TGF-beta mRNA levels were observed in all five ATL cell samples tested; however, in three acute myelogenous leukemia (AML) samples, in one acute lymphatic leukemia (ALL), and one chronic myelogenous leukemia (CML), TGF-beta expression was relatively lower. In normal peripheral mononuclear cells TGF-beta mRNA was weakly detectable. Colony stimulating activity for NRK found in the conditioned medium from ATL cells as well as other leukemia cells correlated well with the levels of TGF-beta mRNA expression. In all three ATL samples tested, stimulation of 3H-thymidine uptake by purified TGF-beta from platelets was apparent. These results suggest that ATL cells are secreting active TGF-beta in a relatively high amount, as compared with other leukemia cells, and may proliferate in response to the factor via an autocrine manner. Furthermore, considering that TGF-beta stimulates bone resorption, we can speculate that the relatively high amount of TGF-beta in ATL cells contributes to the hypercalcemia frequently seen in ATL patients. PMID- 2891389 TI - Acute compartment syndromes of the foot. AB - The early recognition and treatment of impending compartmental ischemia in the foot in the context of severe injuries will prevent the late sequelae of myoneural necrosis. When suspected, simple tests will confirm the diagnosis. If the clinical findings are equivocal, compartment pressure monitoring is an essential diagnostic tool. Methods of measuring compartment pressures in the foot are outlined. Prompt decompression of the compartment syndrome with appropriate fasciotomies either by medial or dorsal longitudinal incisions is indicated to preserve function and form of the foot. PMID- 2891390 TI - Inflammatory bowel disease: the in vitro effect of sulphasalazine and other agents on prostaglandin synthesis by human rectal mucosa. AB - 1. Prostaglandin (PG) E2 and F2 alpha synthesis in vitro by human rectal mucosa was significantly greater in patients with Inflammatory Bowel Disease (IBD) than in controls. 2. The addition of 250 microM sulphasalazine (SASP) significantly increased synthesis by rectal mucosa from patients with IBD, (ulcerative colitis and Crohn's disease) and controls after 1 h of incubation in Krebs' solution at 37 degrees C. 3. Flurbiprofen, indomethacin, sodium salicylate and 5 aminosalicylic acid decreased PGE2 and F2 alpha synthesis. 4. Sodium carbenoxolone decreased PGF2 alpha synthesis but had no effect on PGE2. Disodium cromoglycate, sulphapyridine, salicylazosulphadimidine and methylsulphasalazine had no effect on PG synthesis. 5. The data show marked variations in effect on PG synthesis in vitro of substances that have been investigated clinically for their actions on IBD. PMID- 2891391 TI - Choice of therapy in angina. AB - Ischaemic heart disease is one of the most serious health problems in the Western world. Angina is the commonest symptom and its therapy is still palliative, although complete relief from symptoms can generally be achieved by appropriate drugs or revascularization procedures. The degree of disability caused varies and therapeutic choice depends on patient characteristics and causative factors in the production of angina. This article reviews the management of angina from ischaemic heart disease assuming other causes like valvular disease, congenital anomalies, arteritis and cardiomyopathies have been excluded. PMID- 2891392 TI - Monoamine oxidase inhibitors and narcotic analgesics. A critical review of the implications for treatment. AB - There has been a recent renewal of interest in the use of monoamine oxidase inhibitors, but the concurrent administration of narcotic analgesics is often a cause for concern. This review clarifies the different types of MAOI/narcotic interactions and offers guidelines for the use of narcotic analgesics in the presence of MAOIs. The MAOI/pethidine interaction has two distinct forms: an excitatory and a depressive form. Pethidine must never be used in the presence of MAOIs because of the risk of a fatal excitatory interaction. Morphine does not cause this excitatory interaction, and is the drug of choice provided an allowance is made for possible potentiation of the depressive narcotic effect. It is inevitable that strong analgesia will occasionally be required as an emergency measure in patients on MAOIs, and insufficient attention is paid in psychiatric textbooks to the two different types of interactions and their therapeutic implications. PMID- 2891393 TI - Macrocytosis and sulphasalazine treatment of rheumatoid arthritis. PMID- 2891394 TI - Vascular corrosion casts of the dog testis after experimental microvascular surgical orchiopexy. A scanning electron microscope study. AB - Five mongrel dogs underwent microvascular surgical orchiopexy by anastomosing the testicular artery and vein with the respective caudal epigastric vessels. In order to assess the effect of a 40 to 50-min period of warm ischaemia (the time required to make the anastomosis) on the testicular blood vasculature, plastic corrosion casts were made of the operated testes and compared with non-operated control specimens. The resulting blood vessel casts were inspected in the scanning electron microscope. One case of testicular atrophy developed, caused by a postoperative wound abscess. Comparing operated with non-operated testes, no differences in vascularisation, pattern or density of arterial supply, capillary network and venous drainage were seen. These findings are in agreement with data from the literature concerning histological, hormonal and clinical results. PMID- 2891395 TI - Anatomical findings at orchiopexy. AB - The anatomical findings at orchidopexy for cryptorchid testis were recorded for 60 boys aged between 6 months and 18 years. In 11 patients (18.3%) bilateral cryptorchidism was present. At operation, atrophied testicular tissue was found in two patients and one testis was found to be absent; 69.1% (47/68) of the remaining testes were found in the superficial inguinal pouch at operation, 27.9% (19/68) were in the inguinal canal, one was in the femoral triangle and one was high in the scrotum. In 35 testes (51.5%) there was an associated hernial sac. In 54 testes (79.4%) the gubernaculum testis was attached to an anatomical site other than the lower scrotum. In 26 (38.2%) there was a fascial block to descent into the scrotum and one or other of these findings was present in 64 testes (94.1%). These findings suggest that failure to establish a patent route from the superficial inguinal region to the scrotum and the passage of the gubernaculum along this route are the abnormalities responsible for failure of testicular descent. PMID- 2891396 TI - Torsion of testis following orchiopexy. PMID- 2891397 TI - Kinins. PMID- 2891398 TI - Cryptorchidism in Scotland. PMID- 2891399 TI - Tropical spastic paraparesis associated with human T lymphotropic virus type I in an east African naturalised in Sweden. PMID- 2891400 TI - Cocktail stick injuries: delayed diagnosis of a retained foreign body. PMID- 2891401 TI - Peripheral type benzodiazepine binding sites are a sensitive indirect index of neuronal damage. AB - The effects of excitotoxic lesions on the neuronal marker enzymes choline acetyltransferase and glutamate decarboxylase and on the levels of 'peripheral type' benzodiazepine binding sites (PTBBS) (a putative glial marker) have been compared to see whether PTBBS provide a suitable if indirect quantitative index of neuronal damage. Intrastriatal injection of excitotoxic compounds provoked a dose-dependent increase in the levels of PTBBS. The potency order was the following: kainate greater than AMPA greater than N-methyl-D-aspartate (NMDA) greater than quisqualate. The maximal increases in this parameter were 400, 470, 320 and 210% for kainate (12 nmol), AMPA (100 nmol), NMDA (500 nmol) and quisqualate (250 nmol), respectively. 2-Amino-5-phosphonovalerate (100 nmol)--an antagonist of the NMDA receptor subtype--completely blocked the increase in PTBBS induced by NMDA (250 nmol), but was without effect against the other excitotoxins. Increases in binding levels were in general mirrored by a decrease in choline acetyltransferase and glutamate decarboxylase activity. However, PTBBS were a more sensitive indirect index of neuronal damage than neuronal enzymes because the alterations in binding were statistically significant at doses of excitotoxins lower than those causing a loss of marker enzymes. It is concluded that PTBBS are a suitable and sensitive means of detecting discrete neurotoxic changes and that its measurement will help in the study of other pathological and experimental models. PMID- 2891402 TI - Is octopamine a 'false transmitter'? Regional distribution and serial changes in octopamine and noradrenaline following locus coeruleus lesions. AB - The effects of electrolytic lesions of the locus coeruleus (LC) on endogenous octopamine and noradrenaline levels were observed at various temporal intervals. Noradrenaline was assayed from halved tissue samples by high-performance liquid chromatography (HPLC) while octopamine was determined from the other halves of the brain samples by radioenzymatic assay methods accompanied by chromatographic separation. Brains were dissected into 8 regions: cerebellum, anterior and posterior cortex, hippocampus, hypothalamus, medulla/pons, midbrain and striatum. Assays were performed at postlesion intervals of 4, 8, 13 and 18 days. The rates of depletion of noradrenaline at the tested intervals roughly matched those of octopamine in the anterior cortex, posterior cortex and striatum. In the cerebellum, hypothalamus, hippocampus and pons/medulla, levels of octopamine diminished later than those of noradrenaline, at times showing an initial increase within the first week after the LC lesion. In the midbrain however, this pattern was reversed, octopamine levels initially decreasing in parallel with noradrenaline but subsequently recovering to significantly higher values. The results do not unequivocally support the hypothesis that octopamine is present in the brain solely as a 'false transmitter' in noradrenergic neurones. Neither, however, do they provide clear support for earlier contentions that octopamine is likely to play a role in central neurones as a synaptic transmitter, independent of the noradrenergic system. PMID- 2891403 TI - An ultrastructural description of glutamate-like immunoreactivity in the rat cerebellar cortex. AB - This study provides the first ultrastructural description of glutamate-like immunoreactive neurons and processes in the cerebellar cortex of the rat. Glutamate-like immunoreactivity was seen in parallel fibers, granule cell perikarya, Purkinje cell dendrites, and mossy fiber glomeruli. These data support previous studies that have suggested that granule cells may use glutamate as a neurotransmitter. However, not all granule cells or all parallel fibers were glutamate-like immunoreactive, suggesting that some granule cells may use transmitters other than glutamate. The presence of glutamate-like immunoreactivity in mossy fibers supports the hypothesis that some cerebellar afferent systems may use glutamate as a neurotransmitter. PMID- 2891404 TI - Presence of tyrosine-hydroxylase activity in anterior pituitary adenomas and ectopic anterior pituitaries in male rats. AB - There is evidence for local regulatory effects of dopamine (DA) and norepinephrine (NE) on the release of prolactin (PRL) and other hormones from the anterior pituitaries transplanted to an ectopic site. In order to further explore these suspected regulatory mechanisms and to determine if they may exist also in pituitary tumors, we have examined the activity of tyrosine-hydroxylase (TH) in ectopic pituitaries and in hyperplastic pituitaries of estrogen-treated rats. Adult male rats with a pituitary graft in each kidney and sham-operated controls were examined 5 weeks after surgery. Rats implanted for 3 months with Silastic capsules containing diethylstilbestrol (DES) or with empty capsules were used 10 weeks after the capsules were removed. TH activity in ectopic anterior pituitaries of grafted rats was significantly higher than that measured in the eutopic anterior pituitaries of control animals. Similarly, TH activity was significantly higher in DES-induced pituitary tumors than in control pituitaries. These data support the possible existence of local catecholaminergic mechanism(s) that could be modulating PRL secretion from pituitary tumors and from ectopic pituitaries. PMID- 2891405 TI - Synaptosomal neurotransmitter uptake systems in the retina and brain nuclei of light- and dark-adapted rabbits. AB - High affinity uptake rate for [14C]aspartate and [3H]dopamine by retinal homogenate (H), Pl (outer plexiform layer, OPL), and P2 (inner plexiform layer, IPL) retinal synaptosomal fractions were not significantly different between light- and dark-adapted rabbits. However, there were significant increases in the dark in [3H]gamma-aminobutyric acid high affinity uptake rate by retinal H and P2 but not that of Pl. There was a significantly higher [3H]choline uptake rate by retinal H, Pl and P2 in the dark-adapted compared to light-adapted rabbits, but there was no significant change in this rate for synaptosomal fractions from the lateral geniculate body, superior colliculus, visual cortex (VA I + II), caudate nucleus (CN) and hippocampus (HP). Data obtained in this study, along with reports of others, indicate that the change in retinal neurotransmission functions may not always be parallel with the change in high affinity uptake rates of neurotransmitters by retinal synaptosomal fractions. Data obtained indicate an increase in retinal cholinergic neuronal activities in the dark and indicate that optic nerves are not cholinergic and cholinergic neurons in brain nuclei, such as VA, CN and HP, are not significantly influenced by optic nerve inputs in light and dark conditions. PMID- 2891406 TI - Somatostatin and neuropeptide Y are almost exclusively found in the same neurons in the telencephalon of turtles. AB - In mammals, somatostatin and neuropeptide Y (NPY) are largely found in the same neurons of the telencephalon. To determine if this is a phylogenetically ancient feature of telencephalic organization, the brain of red-eared turtles was examined using immunofluorescence double-labeling procedures. The results showed that somatostatin and NPY are found almost exclusively in the same neurons in the telencephalon of turtles, but these neuropeptides rarely co-occur in neurons outside the telencephalon. Thus, the extensive co-occurrence of NPY and somatostatin appears to be a feature of telencephalic organization that was present in the reptilian common ancestors of mammals and modern reptiles. PMID- 2891407 TI - Identification of serotonergic neurons in human brain by a monoclonal antibody binding to all three aromatic amino acid hydroxylases. AB - A monoclonal antibody, PH8, has been isolated and shown by immunocytochemistry to bind to serotonergic and catecholaminergic neurons in sections of the rat and human brain. In human brain, obtained at autopsy, particular fixation and embedding conditions eliminate the labelling of catecholaminergic neurons while leaving intact the labelling of serotonergic neurons. This property makes the antibody of potential use for structural studies of serotonergic neurons in the normal and diseased human brain. PH8 was raised to pure monkey phenylalanine hydroxylase and has been shown to bind to the 50,000 mol. wt. phenylalanine hydroxylase polypeptide. Immunocytochemical and immunochemical evidence is presented in support of the hypothesis that the labelling of serotonergic and catecholaminergic neurons results from the binding of PH8 to tryptophan and tyrosine hydroxylase, respectively. PMID- 2891408 TI - The distribution of somatostatin-immunoreactive neurons and fibers in the rat cerebral cortex: light and electron microscopic studies. AB - The distribution of somatostatin (SOM)-immunoreactive neurons in rat motor and somatosensory cortices was studied by immunohistochemistry at both light and electron microscopic levels. Three types of SOM-positive neurons were described. Type A cells are large to medium in size, multipolar in shape and have 3-5 long primary cell processes. Type B cells are medium to small, fusiform in shape and have two primary processes. These two subtypes show abundant subcellular organelles and are heavily stained throughout their cytoplasm. Type C cells are small, ovoid or fusiform in shape and are lightly stained. These previously undescribed cells are the largest SOM-immunoreactive population in the cortex. Ultrastructurally they have few subcellular organelles and only a patchy immunostaining in the cytoplasm. SOM-immunoreactive neurons occur in all cortical layers except I, and are most numerous in layer V of the somatosensory and motor cortex. In SOM-positive dendrites, electron-dense immunoreactive/peroxidase end product is primarily associated with microtubules. Fine deposits also occur deep to the postsynaptic membrane asymmetric synapses making contact with such dendrites. PMID- 2891409 TI - Evidence for N-methyl-D-aspartic acid receptor-mediated modulation of the commissural input to central vestibular neurons of the frog. AB - We have investigated the role of N-methyl-D-aspartate (NMDA) receptors in the excitatory synaptic transmission to central vestibular neurons in the isolated superfused brainstem of the frog. In superfusate containing 1 mM Mg2+ field potentials in the vestibular nuclei evoked by electrical stimulation of either the ipsi- or the contralateral VIIIth nerve were not affected by bath-applied D-2 amino-5-phosphonovaleric acid (D-APV, 25-50 microM), a selective NMDA antagonist. In a low Mg2+ solution postsynaptic field potential components were larger than control but still unaffected by D-APV. Ipsi- and contralaterally evoked excitatory postsynaptic potentials (EPSPs) differed in their shape parameters as well as in their pharmacological sensitivity. Ipsilaterally evoked EPSPs were not affected by D-APV and has a rise time that was faster than that of contralaterally evoked EPSPs. The peak amplitude of hte latter was reduced by D APV (25-50 microM) to about 65% of the control value in the presence of 1 mM Mg2+. During bath application of NMDA (100 microM) an increased input resistance and repetitive de- and hyperpolarizing membrane potential shifts were observed. Similar events were observed during a reduction of the Mg2+ concentration. Bath application of NMDA (0.1-1 microM) resulted in an enhanced size of the recorded EPSPs. Dendritic and somatic EPSPs were simulated on a computer with the assumption of a constant NMDA receptor activation and a pulse-like non-NMDA receptor activation. The results of these simulations are consistent with the hypothesis that the efficacy of non-NMDA-mediated vestibular commissural synaptic transmission is modulated through tonically activated NMDA receptors. PMID- 2891410 TI - Differential dopaminergic innervation of the two pallidal segments in the squirrel monkey (Saimiri sciureus). AB - Immunohistochemical studies with an antiserum raised against tyrosine hydroxylase have allowed us to demonstrate a dense dopaminergic innervation of the globus pallidus in the squirrel monkey. This innervation derived mostly from two fascicles that detached themselves from the major ascending dopaminergic bundle arising from midbrain dopamine cell bodies and running in the lateral hypothalamus. Dopaminergic fibers reached the globus pallidus by coursing along its two major output pathways: the lenticular fasciculus dorsally and the ansa lenticularis ventrally. At pallidal levels, dopaminergic fibers abounded in medullary laminae and arborized profusely within the internal pallidal segment, whereas the external pallidum displayed only few short fibers that prevailed in its dorsal portion. These findings provide the first evidence that the primate globus pallidus receives a massive and differentially distributed dopaminergic input. PMID- 2891411 TI - The innervation of intraocular spinal cord transplants by cografts of locus ceruleus and substantia nigra neurons. AB - The nucleus locus ceruleus and the substantia nigra were sequentially cografted with spinal cord in the anterior chamber of the eye of adult rats. The double grafts were allowed to mature in oculo. After a survival time of 2 months, half of the number of rats were sacrificed, the grafts were dissected out and prepared for tyrosine hydroxylase immunohistochemistry and Falck-Hillarp monoamine histochemistry. The remaining animals were sacrificed after 12-14 months and processed according to the same protocol. No ingrowth from the sympathetic ground plexus in the host iris was seen in single spinal cord grafts at any of the survival times. At the shorter survival time there were no or very few catecholaminergic nerve fibers from the locus ceruleus or substantia nigra that were innervating the spinal cord cograft. In double grafts that were allowed to remain in oculo for 12-14 months, the entire spinal cord graft was innervated with varicose, catecholamine-containing nerve fibers. The locus grafts were able to innervate the spinal cord cografts much more densely than the substantia nigra grafts. In conclusion, the results demonstrate that isolated intraocular spinal cord grafts can be innervated by adjacent central catecholamine neurons. However, this is done in a delayed manner as compared to other models. The isolated replicas of descending adrenergic pathways to the spinal cord thus formed should provide useful information about the function of descending spinal catecholamine pathways. PMID- 2891412 TI - The effects of excitatory amino acids and their antagonists on the generation of motor activity in the isolated chick spinal cord. AB - We have investigated the action of excitatory amino acids and their antagonists on spontaneous motor activity produced by an isolated preparation of the chick lumbosacral cord. Bath application of N-methyl-DL-aspartic acid (NMDA) or D glutamate increased the occurrence and duration of spontaneous episodes of motor activity. Both NMDA-induced and spontaneous activity were reversibly inhibited by several excitatory amino acid antagonists including 2-amino-5-phosphono valeric acid and gamma-D-glutamyl glycine in a dose-dependent manner. These results suggest that motor activity in the chick spinal cord may be regulated by the release of endogenous excitatory amino acids from spinal interneurons. PMID- 2891413 TI - Lesions of putative glutamatergic pathways potentiate the increase of inositol phospholipid hydrolysis elicited by excitatory amino acids. AB - The stimulation of inositol phospholipid (PI) hydrolysis by excitatory amino acids was measured in the rat hippocampus or striatum after 3 different chemical or surgical lesions of putative glutamatergic pathways. Intrahippocampal infusions of kainate preferentially destroyed neurons in the CA3-4 areas, denervating the CA1 area of the ipsilateral and contralateral hippocampus. Infusions of colchicine selectively destroyed granule cells of fascia dentata, denervating the CA3 area of the ipsilateral hippocampus. Ablation of the frontal cortex selectively reduced the glutamatergic afferents to the striatum. These 3 lesions potentiated the ibotenate, glutamate and quisqualate stimulation of PI hydrolysis, while N-methyl-D-aspartate remained ineffective. This stimulation was inhibited by 2-amino-4-phosphonobutyric acid but not by phencyclidine. These lesions also increased the stimulation of PI hydrolysis elicited by norepinephrine, but failed to enhance the stimulation by carbamylcholine. These results support the hypothesis that signal transduction in a subclass of excitatory amino acid receptors present in rat brain may undergo plastic modifications following denervation. PMID- 2891414 TI - Somatostatin centrally inhibits vasopressin secretion during haemorrhage. AB - Somatostatin is a hypothalamic inhibiting factor which has been reported to be involved in the regulation of the secretion of several anterior pituitary hormones. To determine if somatostatin plays a role in the control of vasopressin secretion from the posterior pituitary, we examined the effects of intracerebroventricular infusion of somatostatin-14 and a super-active analogue, cyclo-(N-Me-Ala-Tyr-D-Trp-Lys-Val-Phe), on the concentration of plasma vasopressin in response to haemorrhage in conscious sheep. Haemorrhage (15 ml/kg over 15 min) elevated plasma vasopressin. Treatment with either somatostatin-14 or the analogue inhibited the elevation of plasma vasopressin induced by haemorrhage. The inhibition may result from an effect of somatostatin on neurotransmitter afferent inputs to the hypothalamus which trigger vasopressin release during haemorrhage. Our study demonstrates for the first time that somatostatin administered centrally inhibits vasopressin secretion during haemorrhage in the conscious animal. PMID- 2891415 TI - Ro 15-1788, CGS 8216, picrotoxin, and pentylenetetrazol: do they antagonize anxiolytic drug effects through an anxiogenic action? AB - Recent evidence suggests that agents that inhibit GABAergic function, particularly at sites on the GABA/benzodiazepine receptor complex, have intrinsic anxiogenic properties. The present experiments further characterize the behavioral effects of these receptor complex inhibitors, using the "defensive burying" test, which is reasonably selective for anxiolytics. Putative blockers of the GABA-receptor coupled chloride channel, picrotoxin and pentylenetetrazol, and the benzodiazepine receptor antagonists Ro 15-1788 and CGS 8216 each blocked the anxiolytic effect of chlordiazepoxide. However, these compounds failed to exert significant anxiogenic effects in the burying test. These findings suggest that different animal models of anxiolytic drug effects are not equally sensitive to the possible anxiogenic effects of drugs that act at the GABA/benzodiazepine receptor complex. PMID- 2891416 TI - Autoradiographic analysis of muscarinic cholinergic and serotonergic receptor alterations following methamphetamine treatment. AB - Autoradiographic examination of the response of muscarinic cholinergic (M1 and M2) receptors to multiple doses of methamphetamine has been performed in several regions of the rat brain. Both muscarinic receptor subtypes were identified with [3H]-N-methylscopolamine, while M1 receptors were specifically labeled with [3H] pirenzepine. No change in muscarinic receptors labeled with [3H]-pirenzepine was found in any of the brain regions examined following methamphetamine treatment; however, [3H]-N-methylscopolamine binding was significantly reduced (24-40%). These results indicate that M1 receptors remained unchanged after the drug treatment, while M2 receptors were reduced in many areas of the rat central nervous system following multiple high doses of methamphetamine. Five doses of methamphetamine (6-hour interval between doses) were required to elicit the receptor changes in all brain regions analyzed. Within 7 days after drug treatment, the receptor number returned to control values in the affected brain areas. Additionally, the response of serotonin (5-HT1 and 5-HT2) receptors to methamphetamine was examined and found to be reduced in a few brain areas analyzed. The receptor changes were accompanied by METH-induced decreases in tyrosine hydroxylase and tryptophan hydroxylase activities. PMID- 2891417 TI - Localization of D-amino acid oxidase in Bergmann glial cells and astrocytes of rat cerebellum. AB - The localization of D-amino acid oxidase in rat cerebellum was systematically studied in serial fixed sections at the levels of both light and electron microscopy using a coupled peroxidation method based on the intensifying effect of nickel ions. Deposits were only seen in astrocytes and Bergmann glial cells, and not in neuronal components, endothelial cells or ependymal cells. In the molecular layer, heavy deposits were present in the profiles of Bergmann glial processes around the complexes of synapses where the parallel fiber varicosities form synapses with the thorns emerging from the spiny branchlets of Purkinje cell dendrites. In the Purkinje cell layer, the oxidase-containing processes of Bergmann glial cells enveloped basket cell axons, their terminals, the terminals of the recurrent collaterals of Purkinje cell axons and Purkinje cell bodies. In the granular layer, the cerebellar glomeruli were enveloped by the heavily stained processes of astrocytes. Based on this characteristic localization of the oxidase, we discussed the physiological role of the oxidase in connection with the function of glial cells. PMID- 2891418 TI - L-homocysteic acid: an endogenous excitotoxic ligand of the NMDA receptor. AB - L-Homocysteic acid (L-HCA) has been proposed as a natural transmitter at the N methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptor based on recent evidence that L-HCA occurs L-HCA occurs naturally in the mammalian CNS, is released from K+ stimulated brain slices in a calcium-dependent manner and may be contained in nerve terminals located in certain brain regions that have a high density of NMDA receptors. Here we report that L-HCA potently induces a pattern of cytopathology in the ex vivo chick retina which mimics the pattern of NMDA but not kainic acid (KA) neurotoxicity. We also show that known NMDA antagonists, including Mg++, D-aminophosphonopentanoate and certain anesthetics, analgesics, and sedative hypnotics block the neurotoxic actions of L-HCA in direct proportion to their efficacy in blocking NMDA neurotoxicity. While there is a perfect correspondence between agents that block NMDA and L-HCA neurotoxicity, only a few such agents are active against KA neurotoxicity. We find that 3H-Glu binding is inhibited more potently by L-HCA (Ki = 67 microM). Moreover the patterns with which L-HCA and NMDA displace 3H-Glu binding in autoradiograms appear essentially identical. These findings are consistent with the proposal that L-HCA is an endogenous ligand at NMDA receptors. PMID- 2891420 TI - [Vecuronium for intubation and relaxation in cesarean section]. PMID- 2891419 TI - [Appreciation of the quality of and recovery from anesthesia with the combination continuous-flow propofol-alfentanyl]. PMID- 2891421 TI - [Dental mutilations in exotic civilizations and their significance]. PMID- 2891422 TI - Is there a role for renal alpha 2-adrenoceptors in the pathogenesis of hypertension? AB - Current information suggests that alpha 2-adrenoceptors do not directly influence vascular resistance or Na reabsorption in the rat kidney. To reexamine the effects of alpha 2-agonists we used isolated rat kidneys perfused at 37.5 degrees C with precise measurement of renal artery pressure and flow. The recirculating perfusate contained pyruvate as the sole metabolic substrate which enabled us to use gluconeogenesis as an index of proximal tubular alpha 1-responses. Clonidine and guanfacine in 100 nM concentrations decreased phosphate excretion without altering Na, Cl, or K reabsorption or gluconeogenesis; 500 nM concentrations increased vascular resistance and decreased glomerular filtration rate and Na, Cl, and K excretion with no significant effect on gluconeogenesis. Prior thyroparathyroidectomy prevented the antiphosphaturic but not the antinatriuretic or vascular responses. Clonidine, an alpha 2-agonist with some alpha 1-activity, was a more potent vasoconstrictor than methoxamine or guanfacine. In the presence of prazosin (1 microM), norepinephrine (60 nM) stimulated phosphate reabsorption; norepinephrine alone did not stimulate phosphate reabsorption which indicates alpha 1-antagonism of this alpha 2-response to NE. These results and a literature review suggest that increased renal alpha 2-adrenoceptors could raise renal vascular resistance, reduce renin secretion, and antagonize parathyroid hormone effects on Pi, Ca, HCO3, and Na reabsorption to produce a low renin type of hypertension with increased proximal Na reabsorption and abnormal Ca and Pi excretion. PMID- 2891423 TI - Calcium handling in vasoconstriction to stimulation of alpha 1- and alpha 2 adrenoceptors. AB - Vasoconstriction to stimulation of postsynaptic alpha 1- and alpha 2 adrenoceptors involves different mechanisms of Ca2+ mobilization. Alpha 2 adrenoceptor-mediated vasoconstriction in vivo as well as in vitro is invariably and effectively antagonized by Ca2+ channel blockers, such as nifedipine or verapamil, and is therefore primarily carried by influx of extracellular Ca2+. On the other hand, alpha 1-adrenoceptor stimulation has been linked to both influx of extracellular Ca2+ and release of Ca2+ from intracellular stores. The sensitivity of alpha 1-adrenoceptor-mediated vasoconstriction to blockade by Ca2+ channel antagonists depends on how much both mechanisms of Ca2+ mobilization contribute to the contraction process, and varies between vascular tissues and alpha 1-adrenoceptor agonists. The experimental evidence for the differential utilization of Ca2+ in vasoconstriction to alpha 1- and alpha 2-adrenoceptor stimulation is reviewed. PMID- 2891424 TI - Binding of the hydrophilic beta-adrenergic antagonist [3H]CGP-12177 to cardiac tissue slices: characterization and ontogenetic studies in dogs. AB - A new technique was developed to characterize the binding of a hydrophilic beta adrenergic antagonist, [3H]CGP-12177, to 1-mm thick slices of canine cardiac tissue. This technique was used to quantify the density (Bmax) and the affinity (Kd) of these receptors in the right ventricular conus (RVC) and the left ventricle (LV) at day 1 to 6 weeks of age, and in the adult. Binding was found to be reversible, saturable, stereospecific, of high affinity, and thermolabile. There was an increase in the density of beta-adrenergic receptors between day 1 (Bmax = 2.2 +/- 0.3 fmol/mg tissue in RVC and 2.9 +/- 0.8 fmol/mg tissue in the LV) and 2 weeks of age postnatally, after which it remained constant until 6 weeks of age (Bmax = 7.5 +/- 0.4 and 6.8 +/- 0.9 fmol/mg tissue in RVC and LV, respectively); however, by 6 weeks of age it had not reached adult levels (10.3 +/- 1.0 fmol/mg tissue). The affinity of these receptors did not change between early neonatal life (Kd = 1.3 +/- 0.4 nM) and adulthood (Kd = 1.4 +/- 0.2 nM). The density of beta-adrenergic receptors in the RVC was similar to that in the LV. This new method of quantifying beta-adrenergic receptors in cardiac tissue is simple and fast, and requires minimal tissue handling. It proved to be useful in studying the development of cardiac beta-adrenergic receptors with age. PMID- 2891425 TI - Vagal inhibition of gastric acid secretion: evidence for cholecystokinin as the inhibitory transmitter in the mouse stomach. AB - In the mouse isolated stomach preparation, electrical stimulation of vagal preganglionic fibres activated cholinergic excitatory pathways and noncholinergic inhibitory pathways to the gastric glands. Both were blocked by hexamethonium suggesting that there is at least one nicotinic synapse in each. The inhibitory vagal response was blocked by dibutyryl cyclic GMP, an established cholecystokinin antagonist which abolished cholecystokinin-mediated inhibition of acid secretion. It is suggested that there are direct inhibitory vagal pathways to the gastric glands and that cholecystokinin may be the inhibitory transmitter. PMID- 2891426 TI - The influence of higher temperature on dengue-2 virus infected C6/36 mosquito cell line. AB - Dengue-2 virus infection of C6/36 cells was studied at 28 and 37 degrees C. In infected cells maintained at 28 degrees C, syncytial development was seen on day 4 postinfection, whereas at 37 degrees C, extensive syncytial development was seen by 32 h. Extracellular virus titre was found to correlate with the cytopathic changes. Nine Dengue-2 virus specified proteins were observed in polyacrylamide analyses of cytoplasmic extracts of C6/36 infected cells. All the proteins were observed, although in varied intensities by 32 h postinoculation at 37 degrees C and only on day 4 postinoculation at 28 degrees C. The GP60 glycoprotein appeared at 32 h postinfection when the cells were maintained at 37 degrees C and became prominent only on day 5 at 28 degrees C. The results revealed that a higher temperature accelerated the onset of cytopathic effects, hastened the development of virus specified proteins, and also enhanced the titre of extracellular infectious virus. The importance of the accumulation of the envelope protein GP60 for the development of CPE was indicated. PMID- 2891427 TI - Changes in the hydrophobic characteristics of Clostridium perfringens spores and spore coats by heat. AB - The hydrophobic characteristics of Clostridium perfringens NCTC 8679 spores were demonstrated by adherence to toluene in a toluene-aqueous partition system. Spores and spore coat preparations were hydrophobic. Vegetative cells and spores extracted with a dithiothreitol-sodium dodecyl sulfate treatment known to remove spore coats were not hydrophobic. A heat activation treatment (75 degrees C for 20 min) which promotes more rapid spore germination increased the hydrophobicity of intact spores and decreased that of isolated spore coats. The hydrophobic changes were reversed by washing and stabilized by 0.5% glutaraldehyde. Heat induced hydrophobic changes were observed in spore coats prepared from spores that were preheated and washed before rupturing in a buffer containing glutaraldehyde. These results suggest the occurrence of a heat-induced change in the spore coat (possibly in the conformation of a macromolecule) which was stable only within the architectural confines of the intact spore. PMID- 2891429 TI - Sulfasalazine and male infertility. PMID- 2891428 TI - Migraine. AB - Recent advances in migraine therapy include the recognition of analgesic or ergotamine abuse as a cause of chronic daily migraine, the introduction of effective non-narcotic drugs such as chlorpromazine, dihydroergotamine and corticosteroids for the treatment of intractable migraine attacks, the increased number of beta-blockers now recognized as effective prophylactic agents and the introduction of calcium-channel blockers for prophylaxis. There is a sufficient variety of antimigraine drugs, and therapy should be successful for most sufferers. PMID- 2891430 TI - The relationship between anxiety and depression in children: rating scales and clinical variables. AB - The present study examined the relationship between anxiety and depression in children in the context of proposed adult models. The results support the qualitative distinction between anxious and depressed patient groups on subsets of rating scale measures and clinical variables. In contrast to anxious children who were younger, (day patients) had been ill for longer than one year, presented with behavioral problems, and were low on observer ratings of depressive symptoms; depressed children were older, (inpatients) had been ill for less than one year, presented with emotional problems and were high on observer ratings of both anxious and depressive symptoms. The finding that the older depressed children were concurrently anxious while the younger anxious children were not concurrently depressed is discussed from the viewpoint of a hypothesized temporal sequence between anxiety and depression. The implication of this and other related findings are discussed in regard to their importance for differential diagnosis and prognosis. PMID- 2891431 TI - Treatment of heroin withdrawal with guanfacine: an open clinical investigation. AB - The alpha 2-adrenoceptor stimulant, guanfacine, was used to treat, under open conditions, heroin addicts who volunteered to withdraw from heroin usage. Thirty four addicts (29 males, 5 females) aged 17 to 31 years were treated for 5 to 15 days with varying doses of guanfacine (0.03 up to 1.75 mg daily). Efficacy was determined by the "Opiate Withdrawal Checklist" (OWCL), administered several times during the day, and by the Clinical Global Impression (CGI) scale. All symptom categories of the OWCL, except "sleep disturbances" were equally ameliorated by the treatment. According to the CGI, 88% of the cases were judged as having had a very good or good improvement. Tolerability to the medication was judged as good or very good in 94% of the cases. PMID- 2891432 TI - Acromegaly from ectopic growth hormone-releasing hormone secretion by a malignant carcinoid tumor. Successful treatment with long-acting somatostatin analogue SMS 201-995. AB - A 26-year-old man with acromegaly secondary to ectopic growth hormone-releasing hormone (GHRH) secretion by a metastatic carcinoid tumor is the subject of this study. He previously failed to respond to conventional therapeutic modalities (partial hypophysectomy, pituitary irradiation, high-dose bromocriptine and a combination of streptozotocin and 5-fluorouracil) and was treated with long acting somatostatin analogue SMS 201-995 (Sandoz, East Hanover, NJ). Growth hormone and somatomedin C concentrations became normal, and GHRH-LI (GHRH-like immunoreactivity) was suppressed by more than 60%. The growth hormone response to exogenous GHRH 1-40 was stopped and growth hormone rise to thyrotropin-releasing hormone (TRH) was significantly attenuated. A significant shrinkage of the pituitary gland was observed. Similarly, the size of the metastatic carcinoid lesions decreased dramatically and was accompanied by a normalization of liver function. After almost 2 years of SMS 201-995 therapy, the patient was well and had no clinical signs of acromegaly. Thus, SMS 201-995 appears to be a remarkably effective agent for treatment of acromegaly secondary to ectopic GHRH secretion. PMID- 2891433 TI - Absence of gamma-glutamyltranspeptidase activity in lung metastasis in rats with hepatocellular carcinomas induced by ciprofibrate, a peroxisome proliferator. AB - The incidence of lung metastasis in rats with hepatocellular carcinomas (HCC) induced by ciprofibrate, a peroxisome proliferator and the expression of gammaglutamyl transeptidase (GGT) in the metastatic lesions was studied. HCC were induced in 75 male F-334 rats by chronic dietary administration of ciprofibrate (0.025% w/w) for 16-22 months. The incidence of lung metastasis was 25% in rats killed between 14 and 16 months which increased to 56% in rats killed between 20 and 22 months. The lung metastases were multifocal and present in both the blood vessels and parenchyma. All the metastatic foci examined for the expression of GGT by histochemical stain were devoid of this enzyme. The results of this study clearly demonstrate the malignant behavior of ciprofibrate-induced liver tumors and the absence of GGT expression in metastatic lesions a phenotypic property that is peculiar to the primary HCC induced by several peroxisome proliferators. PMID- 2891434 TI - Modulation of tissue and epidermal transglutaminases in mouse epidermal cells after treatment with 12-O-tetradecanoylphorbol-13-acetate and/or retinoic acid in vivo and in culture. AB - Retinoic acid (RA) induces tissue transglutaminase (TGASE) and inhibits terminal differentiation induced either by calcium ion or by the tumor promoter 12-O tetradecanoylphorbol-13-acetate (TPA) in primary mouse epidermal cells in culture. The relevance of these effects on cultured cells to the antipromoting action of RA was investigated in female BALB/c and CD-1 mice in vivo. Tissue TGASE was distinguished from epidermal TGASE on the basis of different thermolability at pH 9 or elution from the anion exchanger Mono Q. After topical application of 3 to 5 micrograms (10 to 17 nmol) of RA to the shaved back skin, the specific activity of tissue TGASE increased up to 30-fold primarily in the basal cell fraction of Percoll-separated epidermal cells. Enzyme activity returned to basal levels by 7 days. Treatment with TPA (10 micrograms or 17 nmol/mouse) induced an increase in epidermal TGASE which reached a maximum at 12 h after application, primarily in suprabasal cells. RA applied 1 h before TPA caused no reduction of TPA-induced epidermal TGASE, but the increase in tissue TGASE due to RA was markedly inhibited by TPA. The effects of TPA and RA on TGASE activities in primary epidermal cells in culture were similar to those in vivo except that RA reduced the induction of epidermal TGASE by TPA. In culture the induction of epidermal TGASE by TPA was independent of Ca2+ concentration in the medium above 0.03 mM, but cornified envelope formation was markedly enhanced by Ca2+ above the level required for maintaining a basal cell population (0.03 to 0.05 mM). The TPA-induced formation of cornified envelope in the presence of elevated Ca2+ was completely inhibited by RA if cells were pretreated with RA for 24 h. Our results are consistent with RA causing a reprogramming of epidermal cells that alters their response to differentiation stimuli. PMID- 2891435 TI - Lack of albumin as genotypic marker of preneoplastic analbuminemic rat hepatocytes transplanted within albumin-positive liver. AB - In analbuminemic rats, preneoplastic hepatocytes lack the capability to produce albumin. On the other hand, the hepatocytes of F1 hybrids born from parents of analbuminemic rats and normal rats retain their capability to produce albumin, since the analbuminemia is inherited as a recessive trait in rats. We isolated hyperplastic nodule cells from Nagase's analbuminemic rats and transplanted them into the livers of F1 hybrid rats by infusion into the mesenteric vein. The host rats were subjected to a short term dietary 2-acetylaminofluorene and underwent a two-thirds partial hepatectomy to promote the growth of preneoplastic hepatocytes. Within 10 to 13 days after transplantation, may albumin-negative hepatocytic nodules were formed in the albumin-positive host livers. Almost all the albumin-negative nodules expressed conventional biochemical markers for preneoplastic hepatocytes. Eight to 9 weeks after the transplantation, almost the same number of albumin-negative nodules were observed as on days 10-13. However, roughly a half of the albumin-negative nodules showed no biochemical markers. The results indicate that the majority of early preneoplastic lesions revert to become phenotypically normal after removal of the promoting stimuli. PMID- 2891436 TI - Cytogenetic and molecular characterization of tumors in nude mice derived from a multidrug-resistant human leukemia cell line. AB - We have evaluated whether selection of a human tumor leukemic line for resistance to vinblastine (Velban; VLB) alters its tumorigenicity. To address this question, CEM and CEM/VLB100 cells [which express the multiple drug-resistant (MDR) phenotype via amplification of the P-glycoprotein gene] were characterized by several techniques including chromosome banding, in situ hybridization, Southern blotting, RNA dot blotting, in vitro drug sensitivity, and tumorigenicity in nude mice. Analysis of the chromosome banding patterns of both drug-sensitive CEM cells and the MDR CEM/VLB100 cells revealed that the two lines differed primarily by the presence of a large metacentric marker chromosome associated with the acquisition of VLB resistance. In situ hybridization of a P-glycoprotein complementary DNA to metaphase chromosomes showed that the amplified P glycoprotein genes in the CEM/VLB100 cell line were localized to this large marker. Tumorigenicity of both the CEM and CEM/VLB100 cell lines was measured after injection of 10(7) cells/nude mouse. The results showed that 4 of 4 drug sensitive and 4 of 5 drug-resistant cell lines formed tumors in 5-10 wk. By comparison with the parental line, three of the four tumors arising from the CEM/VLB100 line retained their drug-resistance properties as measured by vinblastine resistance in vitro and elevated P-glycoprotein mRNA expression associated with P-glycoprotein gene amplification. In addition, tumors retaining the MDR phenotype also retained the large metacentric marker chromosome. One tumor arising from CEM/VLB100 reverted to the drug-sensitive phenotype, with a resultant decrease in P-glycoprotein mRNA expression and loss of P-glycoprotein gene amplification. This revertant was also missing the large metacentric marker present in all cells from the CEM/VLB100 parent. Our experiments show that the acquisition of the MDR phenotype resulting from overexpression of P-glycoprotein in the plasma membrane does not effect the tumorigenicity of human CEM cells. PMID- 2891437 TI - Mechanism of H-ras oncogene activation in mouse squamous carcinoma induced by an alkylating agent. AB - A mouse skin squamous cell carcinoma induced by topical application of the direct acting alkylating agent beta-propiolactone contains an activated H-ras oncogene with an A----T transversion at the second nucleotide of codon 61. The mutation was detected in NIH3T3 transfectant and original tumor DNA by an XbaI restriction enzyme polymorphism and confirmed by oligonucleotide "mismatch" hybridization. The mutation was not seen in the liver of the same animal. The activated oncogene also exhibited several restriction enzyme polymorphisms in transfectant DNA due to a reciprocal translocation 3' to the coding region of the gene, which occurred during transfection. The activating mutation was found in only 1 of 6 beta propiolactone induced mouse skin tumors examined, the only tumor with a transforming H-ras oncogene. This is a much lower frequency of activation than that previously reported for the same tumor type induced by polycyclic aromatic hydrocarbons. The A----T transversion mutation is consistent with a potentially direct mutagenic effect of a specific beta-propiolactone-DNA adduct. PMID- 2891438 TI - erbA-related sequence coding for DNA-binding hormone receptor localized to chromosome 3p21-3p25 and deleted in small cell lung carcinoma. AB - Small-cell lung carcinoma (SCLC) is characterized by a consensus deletion in the short arm of chromosome 3. Using a panel of cell lines and somatic cell hybrids containing various rearrangements involving chromosome 3, we have localized the erbA beta sequence (which codes for a thyroid hormone receptor) to the region 3p21----3p25 which overlaps the consensus deletion in SCLC. Moreover, we have shown by Southern blot analysis that at least one copy of the erbA beta sequence is deleted in all six SCLCs so far studied. Normalized ratios of hybridization intensities of the erbA beta probe to intensities of probes for somatostatin (3q28) and raf(3p24-25) ranged from 0.28 to 0.56 and 0.32 to 0.71, respectively, in the six tumors and tumor lines. In view of the importance of the role these genes are known or suspected to play in biological regulation, our results suggest that the erbA beta sequence is a candidate for a recessive oncogene involved in the genesis of SCLC. PMID- 2891439 TI - Bovine leukaemia: facts and hypotheses derived from the study of an infectious cancer. AB - Bovine leukaemia virus (BLV) is the aetiological agent of a chronic lymphatic leukaemia/lymphoma in cows, sheep and goats. Infection without neoplastic transformation has also been demonstrated in pigs, rhesus monkeys, chimpanzees and rabbits and observed in capybaras and water buffaloes. Structurally and functionally, BLV is a relative of human T lymphotropic viruses 1 and 2 (HTLV-I and HTLV-II) since all three viruses show clear-cut sequence homologies. The pathology of the BLV-induced disease, most notably the absence of chronic viraemia, a long latency period and lack of preferred proviral integration sites in tumours, is similar to that of adult T-cell leukaemia/lymphoma induced by HTLV I. The most striking feature of the three naturally transmitted leukaemia viruses is the X region located between the env gene and the long terminal repeat (LTR) sequence. The X region contains several overlapping long open reading frames, one of which, designated XBL-1, encodes a trans-activator function capable of increasing the level of gene expression directed by BLV-LTR and is most probably involved in genetic instability of BLV-infected cells of the B-cell lineage. The 'genetic instability' may put the cell into a state of fragility, ready to move along a number of stages towards full malignancy. Little is known about these events and their causes and we present some theoretical possibilities. BLV infection has a worldwide distribution. In temperate climates the virus spreads mostly through iatrogenic transfer of infected lymphocytes. In warm climates and in areas heavily populated by haematophagous insects, there are indications of insect-borne propagation of the virus. PMID- 2891440 TI - Naturally occurring leukaemia viruses in wild mice: how good a model for humans? AB - This article presents a historical perspective of the wild mouse leukaemia virus (MuLV) model system in light of the prevailing concepts in the early 1970s when this work was carried out. The epidemiology and natural history of MuLV and its associated lymphoma in wild mice were remarkably predictive of later events associated with human T-lymphotrophic virus infection and adult T-cell leukaemia in man. Striking similarities were noted in the exogenous mode of virus transmission, the regional and familial clustering of virus infection in association with specific lymphomas, the low pathogenicity and long latent period, the neurotropism, the virus stability and the nature of viral integration in resultant lymphomas. The wild mouse model was more accurate than the inbred mouse model in pointing the way to human disease. These results illustrate the importance of studying natural history in the 'real world' and the limitations of laboratory artefacts such as those created by inbreeding of laboratory mice. PMID- 2891441 TI - Phase I trial of taxol in patients with advanced cancer. AB - Taxol is a unique plant-derived antineoplastic agent that appears to exert its cytotoxic effect by interfering with microtubule structure and function. In this phase I trial, in which the drug was given as a brief iv infusion every 3 weeks, the dose-limiting toxicity was leukopenia, with thrombocytopenia being seen much less frequently. Sensory neuropathy was frequently seen at the highest dosage, with numbness and paresthesias appearing in a glove-and-stocking distribution. In some cases, this appeared to be a cumulative effect. Total alopecia was common. Other toxic effects observed included nausea and vomiting, mucositis, myalgias, and phlebitis. The frequent occurrence early in the study of acute cardiovascular and pulmonary toxicity suggestive of hypersensitivity reactions was decreased in frequency and severity by prolonging the infusions and premedication with corticosteroids and antihistamines. Two heavily treated patients appeared to respond to this agent, one with non-small cell lung cancer and one with ovarian cancer. Based on these data, we recommend a starting dose in phase II trials of 212 mg/m2 in patients with minimal prior therapy and 170 mg/m2 in heavily treated patients. At least initially, these trials should be carried out in institutions familiar with the use of this drug. PMID- 2891442 TI - Phase I study of taxol administered as a short i.v. infusion daily for 5 days. AB - Taxol inhibits cell division by promoting the assembly and stabilization of microtubules. This report describes the results of a phase I trial of taxol administered as a short iv infusion daily for 5 days every 4 weeks. Sixteen patients with refractory malignancy received 21 courses of taxol at five doses between 5 and 40 mg/m2/day X 5. The first nine patients received taxol as a 60 minute infusion. Two patients experienced anaphylactoid reactions, one at the 5 mg/m2/day and the second at the 15-mg/m2/day X 5 dose levels. These reactions were characterized by facial flushing, tachypnea, and hypotension within several minutes of drug administration. These anaphylactoid reactions occurred on the first day of treatment in the first patient and on the first day of the second course in the second patient. These reactions may be related to the rapid administration of the polyoxyethylated castor oil (Cremophor EL) vehicle in which taxol is formulated. No anaphylactoid reactions were observed in the seven patients who received taxol as a 6-hour infusion with antihistamine and prednisone premedication. Dose-related myelosuppression was seen; leukopenia (wbc count less than 1000/mm3) and granulocytopenia (granulocytes less than or equal to 200/mm3) occurred on Days 8 and 9 in two of two patients treated at the 40 mg/m2/day X 5 level. Thrombocytopenia was mild, with a platelet nadir of 87,000 95,000/mm3 at the highest dose level. Premedication with glucocorticoids and antihistamines coupled with a prolonged 6-hour infusion permitted taxol to be administered at 30 mg/m2/day X 5 safely without immediate life-threatening reactions. PMID- 2891443 TI - Total synthesis of X hapten, III3 Fuc alpha-nLc4 Cer. AB - Total synthesis of O-beta-D-galactopyranosyl-(1----4)-O-[alpha-L- fucopyranosyl- (1----3)]-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----3)-O-beta- D- galactopyranosyl- (1----4)-O-beta-D-glucopyranosyl-(1----1)-2-N-tetracosanoyl (2S,3R ,4E)- sphingenine was achieved by use of the key glycosyl donors O (2,3,4,6-tetra-O-acetyl-beta-D- galactopyranosyl)-(1----4)-O-[(2,3,4-tri-O-acetyl alpha-L-fucopyranosyl) - (1----3)]-O-(2- acetamido-6-O-acetyl-2-deoxy-beta-D glucopyranosyl)-(1----3)-O-(2,4,6-tr i-O- acetyl- beta-D-galactopyranosyl)-(1--- 4)-2,3,6-tri-O-acetyl-alpha-D-glucopyrano syl trichloroacetimidate and fluoride, as well as key glycosyl acceptor 3-O-benzoyl-2-N-tetracosanoyl- (2S,3R,4E) sphingenine, in an unambiguous manner. PMID- 2891444 TI - [Action of famotidine, a new H2-receptor antagonist, on the papillary muscle and atrium of the guinea pig, in vitro]. PMID- 2891445 TI - Percutaneous transluminal angioplasty involving internal mammary artery bypass grafts: a femoral approach. AB - Percutaneous transluminal coronary angioplasty is an effective technique for the treatment of selected patients with ischemic heart disease due to coronary artery stenosis. Successful angioplasty in saphenous vein bypass grafts has been documented, but little experience has been reported using angioplasty in internal mammary artery to coronary artery bypass grafts. Nine of ten patients with stenosis in the internal mammary artery to coronary artery anastomosis or in the coronary vessel distal to the anastomosis site were successfully treated with angioplasty. One patient developed restenosis 1 month after the procedure, and a repeat angioplasty was successful. In one patient, the balloon catheter could not be advanced through the left internal mammary artery to the stenosis site. Technical features of internal mammary artery angioplasty are discussed, including the use of specially designed guiding wires, guiding catheters, and balloon catheters that facilitate angioplasty involving internal mammary arteries from the femoral approach. PMID- 2891446 TI - Regulation of antibody secretion by hybridoma cells. I. Suppression of antibody secretion by coculture of hybridoma cells with idiotype-induced suppressor cells. AB - In this study, we have demonstrated that antibody secretion by hybridoma cell lines can be down-regulated by idiotype-specific immune spleen cells or by nylon wool nonadherent spleen cells. This suppression of antibody secretion can be abolished by treating the idiotype-specific immune spleen cells with anti-Thy 1.2 plus complement. The hybridoma we used for most of our experiments secretes IgM specific for the cross-reacting haptens 2,4,6-trinitrophenyl (TNP) and 2,4 dinitrophenyl (DNP). Suppression was achieved by direct coculture of hybridoma cells with immune cells from animals which were injected with affinity-purified hybridoma antibody-coupled syngeneic spleen cells. The suppressed and control cultures contained similar numbers of viable hybridoma cells, suggesting that a simple cytotoxic effect is not responsible. Idiotype specificity was established in experiments showing that two idiotype immune animals immunized with antibody from two different IgM anti-TNP hybridomas could suppress the hybridoma to which they were immunized but could not affect the other hybridoma. Immune spleen cells required 3-4 days of coculture with hybridoma cells before maximum suppression was achieved. The kinetics of the response suggest that the final effector suppressor cell is generated during the coculture period and that a second signal, perhaps a product of the hybridoma cells, may be required. PMID- 2891447 TI - Axonal tubulin and microtubules: morphologic evidence for stable regions on axonal microtubules. AB - Biochemical studies indicate that axonal tubulin is composed of at least two distinct pools that differ in cold solubility and biochemical composition [Brady et al: J. Cell Biol. 99:1716-1724]. To determine the morphologic correlate of cold-insoluble tubulin, segments of rat optic nerves were exposed to a series of in vitro experimental conditions that affect microtubules (MTs), including cold, podophyllotoxin (PT), triflupromazine (TFP), and taxol, and then examined by electron microscopy. Longitudinal sections of control axons showed MTs oriented parallel to the long axis of the axons. Axons exposed to cold, PT, and TFP showed short segments of MTs in association with cytoskeletal disarray. Morphometric studies were used to distinguish between a simple malorientation of MTs (undulation or zigzags in their course) and the loss of labile segments of MTs, leaving the stable portions behind. The lengths of MT segments were measured in longitudinal sections, and the numbers of MTs were determined in the cross sections. All MT segment-length histograms showed a unimodal distribution. Cold and PT produced a simple shift of the control histogram to the shorter length MTs. In cross sections the numbers of MTs in cold- and PT-exposed axons were significantly decreased, indicating that the presence of short segments of MTs in the longitudinal plane of sections was due to a loss of portions of MTs. Taxol, an agent that promotes MT assembly, reversed the cold effect partially and resulted in increases in both MT segment length and number. These studies indicate that stable MT segments are portions of longer MTs containing both stable and labile regions. Furthermore, these findings are consistent with the hypothesis that cold-insoluble tubulin functions as a transportable MT-organizing complex in the axon. PMID- 2891448 TI - "Pull" and "push" in neurite elongation: observations on the effects of different concentrations of cytochalasin B and taxol. AB - Neurite elongation involves two distinct cytoskeletal functions the "push" of anterograde transport of the cytoskeleton and associated organelles to the neurite tip, and the "pull" exerted by protrusion and generation of tensions in the growth cone. We investigated the roles of these two activities in neurite elongation via the drugs taxol and cytochalasin B (CB), which act on the key cytoskeletal components, microtubules and actin filaments, respectively. When neurons are treated with concentrations of CB below 0.2 micrograms/ml, neurite elongation, growth cone protrusion, and neurite tension are all inhibited in a similar concentration dependent manner. Protrusive activity and tensions are absent at CB concentrations above 0.3 micrograms/ml, yet neurite elongation continues at a plateau level. Thus, "pull" does modulate, but it is not required for neurite elongation. Surprisingly, the inhibitory effects of taxol on neurite elongation are removed by the addition of CB at levels that substantially disrupt the actin filaments of neurites. The neurites extended by taxol-CB neurons are unbranched and curiously unattached to the substratum. When CB is added to taxol treated neurons, neurite extension begins rapidly, even if protein synthesis is severely reduced. We propose that taxol inhibits microtubule transport in neurites, and this inhibition of "push" is reversed by the disruptive effects of CB on the cytoplasmic matrix, allowing taxol-induced microtubule bundles to be transported distally. PMID- 2891449 TI - Microinjected carboxylated beads move predominantly poleward in sea urchin eggs. AB - Observations on living mitotic cells have suggested that material in the spindle moves poleward during mitosis. In order to investigate this movement, sea urchin eggs have been microinjected with 0.25-micron diameter carboxylated fluorescent beads. When fluorescent beads were injected into unfertilized Lytechinus variegatus eggs, no motility was detected. When injected into mitotic cells, beads moved to the spindle poles. Individual beads moved rapidly, in a saltatory fashion, and followed generally linear paths. Beads appeared to move along astral fibers, were generally excluded from the spindle proper, and accumulated at the spindle poles. Some dispersion of the beads away from the pole was observed as cells completed mitosis, but the majority of beads retained a polar location. After depolymerization of spindle microtubules with nocodazole, some dispersion of beads into the cytoplasm was also observed. Beads moved along taxol-induced astral microtubules and accumulated at astral centers. These observations reveal that negatively charged beads accumulate rapidly at mitotic centers, moving toward the minus end of the microtubules. Neither the bidirectional motility of similar beads in interphase cells nor the plus-end-directed bead motility seen in axons was observed in these mitotic cells. PMID- 2891450 TI - Overuse injuries in sport: the foot. AB - The authors discuss the clinical characteristics and treatment of such overuse injuries of the foot as plantar fasciitis, Haglund's syndrome, Jones' fracture, and tarsal navicular stress fractures. A consideration of orthotic devices is also provided. PMID- 2891451 TI - [Traditional Chinese medicine combined with Western medicine in the treatment of epidemic hemorrhagic fever]. PMID- 2891452 TI - Hemodynamic and neural mechanisms of action of thyrotropin-releasing hormone in the rat. AB - The mechanisms mediating the effects of thyrotropin-releasing hormone (TRH) on the cardiovascular system were studied in the conscious rat. Intracerebroventricular (i.c.v.) injection of TRH (8 pmol-80 nmol/kg) induced dose-dependent increases in mean arterial pressure, heart rate, and cardiac index. Hindquarter blood flow increased due to vasodilation, while an increase in renal and mesenteric vascular resistance caused a decrease in blood flow in the respective organs. The plasma levels of norepinephrine and epinephrine were increased by TRH, while there was no change in plasma renin activity or vasopressin. The cardiovascular actions of i.c.v. TRH were not influenced by blockade of the renin-angiotensin system or vasopressin receptors. The ganglion blocker chlorisondamine and the alpha 1- and alpha 2-adrenoreceptor antagonist phentolamine (2 mg/kg i.v.) abolished the increase in blood pressure and mesenteric vasoconstriction after i.c.v. TRH. Propranolol (2 mg/kg i.v.) blocked the TRH-induced increase in cardiac index, heart rate, and hindquarter blood flow. The hindquarter vasodilation induced by TRH was also blocked by the selective beta 2-adrenoceptor antagonist ICI 188,551 (1 or 2 mg/kg i.v.), while the beta 1-adrenoceptor blocker practolol (10 mg/kg i.v.) had no effect on the hindquarter vasodilation produced by TRH but totally blocked the increase in cardiac index. In adrenal demedullated rats, the systemic hemodynamic effects of i.c.v. TRH were diminished along with the decrease in renal blood flow and increase in renal vascular resistance; however, the increase in hindquarter blood flow was attenuated only in adrenal demedullated rats pretreated with the sympathetic blocker bretylium. The renal vasoconstriction induced by i.c.v. TRH was not abolished by renal denervation. In sinoaortic debuffered rats, the pressor, tachycardic, and mesenteric vasoconstrictor responses to centrally administered TRH were significantly potentiated. Taken together, these data suggest that the putative neurotransmitter TRH may play a role in central regulation of cardiac functions and organ blood flow distribution through both the sympathetic nerves and the adrenal medulla. A pivotal role for beta 2 adrenoceptors in mediation of hindquarter vasodilation is also demonstrated. PMID- 2891454 TI - In situ analysis of alpha-adrenoceptors on arteriolar and venular smooth muscle in rat skeletal muscle microcirculation. AB - The purpose of this study was to determine whether both alpha 1- and alpha 2 adrenergic receptors exist on vascular smooth muscle of microvessels and whether adrenergic constriction of anatomically distinct microvascular segments is differentially subserved by either receptor subtype. The cremaster skeletal muscle of anesthetized rats was acutely denervated and suspended in a Krebs bath containing cocaine, normetanephrine, and propranolol to block uptake1, uptake2, and beta-receptors, respectively. Intravital microscopy was used to study large distributing arterioles (mean diameter, 100 microns), small precapillary arterioles (25 microns), and capacitance venules (140 microns). Concentration response (diameter change) curves were obtained for bath-added agonists norepinephrine (mixed alpha 1/alpha 2), phenylephrine (alpha 1), and B-HT 933 (alpha 2) in the absence or presence of antagonists prazosin (alpha 1) and yohimbine (alpha 2). Apparent pD2(-log ED50) values for large arterioles and venules were, respectively, as follows: norepinephrine (7.41 and 7.15), phenylephrine (5.95 and 5.41), and B-HT 933 (5.05 and 5.06). Low concentrations of prazosin (10(-8) M) and yohimbine (10(-7) M) produced receptor subtype selective antagonism and parallel, dextral displacement of norepinephrine curves for large arterioles and venules. The large arteriole pKB (-log KB) was 7.83 +/- 0.65 for prazosin and 7.36 +/- 0.46 for yohimbine. Higher concentrations of prazosin (10(-7) and 3 X 10(-7) M) and yohimbine (10(-6) M) produced further dextral but nonparallel displacement of norepinephrine curves. In contrast, receptor subtype-selective concentrations of only yohimbine inhibited adrenergic constriction of small, precapillary arterioles; but prazosin had no effect at receptor subtype-selective concentrations. These data suggest that adrenergic regulation of large arterioles and venules in skeletal muscle uses both alpha 1- and alpha 2-adrenoceptors. Precapillary arterioles, however, may be subserved predominantly by alpha 2-receptors. PMID- 2891453 TI - Attenuation of the reflex pressor response to muscular contraction by an antagonist to somatostatin. AB - Although group III and IV fibers are known to compose the afferent pathway of the reflex arc causing the pressor response to static muscular contraction, little is known about the neurotransmitters released by these muscle afferents. Somatostatin might be one of these neurotransmitters because this peptide is found in the terminals of fine afferent fibers ending in the dorsal horn of the lumbar spinal cord. Therefore, in chloralose-anesthetized cats, the reflex pressor response to static contraction was examined before and after subarachnoid injections onto the lumbosacral cord of a peptide antagonist to somatostatin. We found that before giving the antagonist, the pressor response to contraction of the triceps surae muscles in 12 cats averaged 33 +/- 4 mm Hg, while 37 +/- 7 minutes after giving the antagonist, the pressor response averaged only 18 +/- 3 mm Hg (p less than 0.001). In contrast, the antagonist to somatostatin had no effect on either the pressor response to electrical stimulation of the cut central end of the sciatic nerve or the pressor response to stimulation of the posterior diencephalon. Furthermore, subarachnoid injection of a peptide antagonist to luteinizing hormone-releasing hormone had no effect on the reflex pressor response to static contraction. Our findings are consistent with the hypothesis that somatostatin plays a role in the spinal transmission of the contraction-induced pressor reflex arising from hind limb skeletal muscle. PMID- 2891455 TI - Variation of urinary enzymes N-acetyl-beta-glucosaminidase, alanine aminopeptidase, and lysozyme in patients receiving radio-contrast agents. AB - A urinary enzyme pattern consisting of two lysosomal enzymes, N-acetyl-beta glucosaminidase and lysozyme, and one enzyme originating from kidney tubular brush border membrane, alanine-aminopeptidase, were studied in 30 patients undergoing intravenous urography and arteriography. N-acetyl-beta-glucosaminidase and lysozyme showed the greatest diagnostic sensitivity and were still abnormal on the fifth day after the administration of radio contrast agent. The results, which are statistically significant (Student's t test), suggest that radio contrast agents are potentially nephotoxic. PMID- 2891456 TI - Urinary enzyme activities in patients treated with gold and other antirheumatic drugs. AB - We have studied 48 rheumatoid arthritis (RA) patients treated with nonsteroidal antiinflammatory drugs (NSAIDs), except salicylates, in 31 of whom parenteral gold was associated as therapeutic agent. In order to assess initial tubular involvement, the activities of some urinary enzymes were measured: N acetylglucosaminidase (NAG, EC 3.2.1.30), microsomal amino-peptidase (MAP, EC 3.4.11.2) and gamma-glutamyltransferase (GGT; EC 2.3.2.2). Results were compared with a control group of 51 subjects of similar age, with no rheumatic symptoms and normal renal function. Both groups of patients (31 with gold therapy and 17 without) showed a significantly increased activity of NAG in urine, but the increase was greater in those treated with gold. MAP and GGT were not elevated significantly in either group. There was no correlation, however, between the increase of NAG and the cumulative dose of gold. NAG, MAP and GGT activities in serum yielded no relevant information. All the usual tests of renal function were also normal. Determination of NAG in urine may be regarded as a sensitive test, capable of detecting selective involvement of renal tubular cells, whose final diagnostic and prognostic significance merits further evaluation. PMID- 2891457 TI - Artifacts in RFLP analyses of human DNA samples co-precipitated with t-RNA. PMID- 2891458 TI - A rapid and efficient screening method for DNA restriction fragment length polymorphisms. AB - Genomic loci displaying DNA sequence polymorphisms represent useful landmarks on the genetic linkage map. We describe an integrated experimental approach to facilitate the detection of DNA restriction fragment length polymorphisms (RFLP) with useful allelic frequencies at loci covered by cloned DNA sequences. The essential feature of the screening method presented is the pooling of DNA from unrelated individuals for Southern blot hybridization analyses using non repetitive DNA sequences identified in and preparatively isolated from genomic lambda phage clones. This procedure results in the detection of RFLP with maximal values of heterozygosity while counterselecting for RFLP with unfavourable allelic frequencies. The described experimental protocol should therefore facilitate the identification and characterization of polymorphic loci with frequent heterozygosity. PMID- 2891459 TI - T cell receptor beta chain polymorphisms are associated with insulin-dependent diabetes. AB - We investigated the T cell receptor constant beta chain (TCR C beta) genes of patients with insulin dependent diabetes mellitus (IDDM) using DNA restriction fragment length polymorphism (RFLP) analysis. Genomic DNA from patients and controls was digested with the restriction endonuclease Bg1 II and transferred to nylon filters using the Southern blot procedure. This enzyme identifies a polymorphic site between the two TCR C beta chain genes. We have found a highly significant increase in the frequency of the 10.0; 9.2 kilobase heterozygous phenotype in patients with IDDM (62.7% versus 42.0% in normal controls; P = 0.0006). In identical twin pairs, this association was most striking in those concordant for IDDM (79.2% versus 42.0% in controls; P = 0.0006). PMID- 2891460 TI - Antibody-directed affinity therapy applied to the immune system: in vivo effectiveness and limited toxicity of daunomycin conjugated to HPMA copolymers and targeting antibody. AB - The applicability of targeting therapy intervention in lymphatic tissue was studied. The effect was measured as the inhibition of anti-sheep red blood cell antibody response expressed in plaque-forming cells. Daunomycin was used as the effective drug and polyclonal and monoclonal anti-Thy 1.2 or anti-Iak antibody served for targeting. Both components were coupled to a soluble N-(2 hydroxypropyl)methacrylamide (HPMA) copolymer with oligopeptidic side sequences which permitted a controlled release of the drug in the target tissue. HPMA copolymer conjugates with side sequences Gly-Phe-Leu-Gly cleavable by lysosomal enzymes decreased in vivo the antibody reaction by 60-85%. A comparable amount of free targeting antibody was without a significant effect. Injection of targeted daunomycin decreased the toxicity of the drug against hematopoietic precursors in bone marrow colony-forming unit-spleen 80 times compared to the same amount of free drug. The in vivo effectiveness of targeted daunomycin was confirmed morphologically. Application of free daunomycin lead to a significant irritation of Kupffer cells in liver while none of the daunomycin-antibody-copolymer conjugate had such an effect. PMID- 2891462 TI - A three-year prospective study of systemic manifestation in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) as a systemic disease can attack many other organs in addition to the joints. A variety of pathological lesions of the blood vessels are responsible for the extra-articular features (EAF). In the present study, we investigated firstly whether the presence of blood vessel changes in one organ- namely the skin--may indicate blood vessel pathology and, consequently, EAF in other organs. Secondly, we investigated the number of EAF in individual patients with RA, and observed whether this changed during the course of the disease. Fifty-one RA-patients (40 female, 11 male; ages had a mean of 49.5, minimum 19, maximum 73 years; mean duration of RA was 7.3, minimum 0.25, maximum 41 years) were included in the study. Punch biopsies from the posterior calf were examined immunohistologically for vessel wall immune deposits. Further, EAF were determined by means of instrumental clinical methods such as pulmonary function test, echocardiography, electromyography, and nerve conduction velocity measurement. At the first investigation 21/51 patients had skin vessel wall immune deposits (SVWID). Five patients--all showed SVWID at first investigation- died during the three-year investigation period, 10 patients could not be followed-up for unknown reasons; the skin biopsy of one patient could not be assessed. At the final investigation, we found SVWID in 11/35 patients. SVWID positive patients had more EAF compared to SVWID-negative patients; this was true both, at the first investigation (1.85 EAF/patient vs 1.05 EAF/patient) and at the final investigation (1.91 EAF/patient vs 0.67 EAF/patient).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891463 TI - Comparison of ophthalmic beta-blocking agents. AB - Glaucoma is described, and the chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of betaxolol and levobunolol in comparison with timolol are reviewed. Betaxolol and levobunolol are two beta-adrenergic blocking agents being marketed as ophthalmic solutions for treatment of primary open-angle glaucoma (POAG) and ocular hypertension (OHT). Betaxolol is a relatively cardioselective beta-adrenergic blocker, while levobunolol is a nonselective beta-adrenergic blocking agent. Double-blind comparative trials have suggested that betaxolol has an equal to slightly lower efficacy and levobunolol has equal efficacy in reducing intraocular pressure (IOP) compared with timolol, the first ophthalmic beta blocker. A mean reduction in intraocular pressure of 15-35% occurs with both betaxolol and levobunolol and is reported to be maintained with prolonged use. Betaxolol is associated with a higher (25%) incidence of local ocular adverse reactions than timolol. However, betaxolol produces less systemic beta 2- and possibly beta 1-adrenergic receptor blockade than either timolol or levobunolol. Betaxolol may be relatively safer to use in patients with reactive airway disease than either timolol or levobunolol. Levobunolol causes a similar to greater incidence of local ocular adverse reactions and similar systemic beta blockade compared with timolol. Levobunolol may possibly be longer acting than timolol, allowing more patients to be controlled by once-daily dosing. Betaxolol and levobunolol appear to be similar to timolol in controlling IOP in patients with POAG and OHT; additional experience with these agents is needed to assess the advantages and disadvantages of each agent. PMID- 2891465 TI - The pro alpha 1 (IV) collagen gene is linked to the D13S3 locus at the distal end of human chromosome 13q. PMID- 2891464 TI - Recognition and treatment of attention deficit disorder. AB - The proposed etiologies, clinical features, prognosis, and drug therapy of attention deficit disorder (ADD) are reviewed. Attention deficit disorder is a common neurobehavioral problem in children that manifests as hyperactivity, impulsivity, and inattention. It may persist into adolescence and adulthood and predispose the patient to antisocial and substance-abuse disorders. Stimulant agents are the drugs of first choice for pharmacologic treatment of ADD. Methylphenidate is the most frequently used stimulant because of its reduced potential for abuse and less troublesome adverse effects compared with dextroamphetamine. Stimulant medications are usually well tolerated, with nervousness and insomnia being the most common adverse effects. The potential for stimulant-induced growth suppression during long-term treatment should be dealt with prospectively by providing drug holidays. Tricyclic antidepressants and monoamine oxidase inhibitors may be used in patients who do not respond adequately to stimulant agents. Low doses of the antipsychotic agents haloperidol, chlorpromazine, or thioridazine may be used as adjunctive treatment for ADD symptoms of hyperactivity and aggressiveness. Attention deficit disorder is not a benign disorder that children necessarily outgrow. Pharmacologic therapy should be combined with nonpharmacologic therapy to provide the greatest long term benefits. PMID- 2891461 TI - The pharmacokinetics of lignocaine and beta-adrenoceptor antagonists in patients with acute myocardial infarction. AB - Lignocaine (lidocaine) and beta-adrenoceptor antagonists are widely used after acute myocardial infarction. The therapeutic value of these agents depends on the achievement and maintenance of safe and effective plasma concentrations. Lignocaine pharmacokinetics after acute myocardial infarction (MI) are controlled by a number of variables. The single most important is left ventricular function, which affects both volume of distribution and plasma clearance. Other major factors include bodyweight, age, hepatic function, the presence of obesity, and concomitant drug therapy. Lignocaine is extensively bound to alpha 1-acid glycoprotein, a plasma protein which is also an acute phase reactant. Increases in alpha 1-acid glycoprotein concentration occur after an acute MI, decreasing the free fraction of lignocaine in the plasma and consequently decreasing total plasma lignocaine clearance without altering the clearance of non-protein-bound lignocaine. Complex changes in lignocaine disposition occur with long term infusions, and therefore early discontinuation of lignocaine infusions (within 24 hours) should be undertaken whenever possible. Because the risk of ventricular tachyarrhythmia declines rapidly after the onset of an acute MI, lignocaine therapy can be rationally discontinued within 24 hours in most patients. Lignocaine has a narrow toxic/therapeutic index, so that pharmacokinetic factors are critical in dose selection. In contrast, beta-adrenoceptor antagonists' adverse effects are more related to the presence of predisposing conditions (such as asthma, heart failure, bradyarrhythmias, etc.) than to plasma concentration. The pharmacokinetics of beta-adrenoceptor antagonists are important to help assure therapeutic efficacy, to provide information about the anticipated time course of drug action, and to predict the possible role of ancillary drug effects (such as direct membrane action) and loss of cardioselectivity. Lipid solubility is the main determinant of the pharmacokinetic properties of a beta-adrenoceptor antagonist. Lipid-soluble agents like propranolol and metoprolol are well absorbed orally, and undergo rapid hepatic metabolism, with important presystemic clearance and a short plasma half-life. Water-soluble drugs like sotalol, atenolol, and nadolol are less well absorbed, and are eliminated more slowly by renal excretion. Clinical assessment of beta-adrenoceptor antagonism is more valuable than plasma concentration determinations in evaluating the adequacy of the dose of a particular beta-adrenoceptor antagonist.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2891466 TI - The use of beta-adrenergic blocking agents, i.v. nitrates and calcium channel blocking agents following acute myocardial infarction. PMID- 2891467 TI - Fluid secretion by gallbladder mucosa in experimental cholecystitis is influenced by intramural nerves. AB - The normal fluid absorption across the gallbladder mucosa is, in experimental cholecystitis, changed to an active net fluid secretion. This fluid secretion, studied in anesthetized cats, is not abolished by extrinsic gallbladder denervation and is unaffected by atropine but is strongly reduced by intraarterial tetrodotoxin or intraluminal administration of lidocaine hydrochloride. Intravenous somatostatin or hexamethonium administration also reduce this secretion. Indomethacin, known to abolish this fluid secretion, did not further reduce it when administered after nerve blocking agents in the present study. These data demonstrate that the prostaglandin-induced gallbladder fluid secretion in experimental cholecystitis is influenced by intramural nerves. It is suggested that gallbladder inflammation is associated with prostaglandin induced activation of intrinsic nerves which may stimulate the epithelial cells to fluid secretion. In the obstructed gallbladder, this secretion causes gallbladder distension by increasing the intraluminal pressure. This mechanism may have a key role in the pathophysiology of acute cholecystitis. PMID- 2891468 TI - Possible mode of action of 5-aminosalicylic acid. AB - Despite the extensive use of sulfasalazine (SAS) and/or 5-aminosalicylic acid (5 ASA) in patients with inflammatory bowel disease and, more recently, rheumatoid arthritis, their mode of action has not been elucidated so far. None of the numerous pharmacological and biochemical effects described, including immunosuppressive, antifolate, and modulatory actions on lymphocyte and leukocyte functions, could be defined unequivocally as mediating their beneficial activity. Recently, interest has focused on actions of SAS and 5-ASA on the various enzymes of the arachidonic acid cascade. Mucosa of patients with inflammatory bowel disease generates excessive amounts of cyclooxygenase products such as prostaglandins (PG) as well as 5-lipoxygenase products such as leukotriene (LT) B4 and sulfidopeptide-LT. Both PG and LT exert proinflammatory actions and are potentially important mediators of mucosal inflammation. SAS and 5-ASA, however, have been found to inhibit PG synthesis under certain experimental conditions only, while increasing PG formation under other conditions. While SAS was found to inhibit colonic LTB4 synthesis, 5-ASA was reported to selectively affect the cyclooxygenase pathway of arachidonate metabolism in this tissue. Our results demonstrate that, like the parent compound, the metabolite 5-ASA in a dose dependent manner inhibits release of LTB4 and sulfidopeptide-LT from normal human colonic mucosa (IC50 3.5 and 3.7 mmol/liter, respectively). Indomethacin, which has no efficacy in the treatment of patients with inflammatory bowel disease, on the other hand, selectively inhibited PGE2 formation in normal and inflamed colonic mucosa (IC50 1.7 and 1.0 mmol/liter, respectively) without reducing synthesis of LTB4 or sulfidopeptide-LT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891469 TI - Oral 5-aminosalicylic acid preparations in treatment of inflammatory bowel disease. An update. AB - Therapeutic efficacy of 5-aminosalicylic acid (5-ASA) preparations is reviewed. In the acute treatment of Crohn's disease, Pentasa and Salofalk seem to be more effective than placebo. When it is given in an equimolar 5-ASA regimen, Salofalk appears to be at least as effective as sulfasalazine (SAS) in the treatment of both Crohn's disease and ulcerative colitis. Asacol and SAS are equally effective in maintenance therapy of ulcerative colitis. Dipentum was more efficient than placebo. There was only a low incidence of side effects from oral 5-ASA preparations, but larger-scale trials may be needed for a more accurate profile of adverse reactions. PMID- 2891470 TI - Accuracy of C-peptide:insulin molar ratio as a measure of hepatic removal of insulin. AB - We measured transhepatic C-peptide and insulin concentrations in plasma, and hepatic removal of insulin, to examine whether the practice of reporting the C peptide:insulin molar ratio as a measure of the hepatic removal of insulin is valid. In anesthetized dogs (n = 6), during electromagnetic hepatic blood flow monitoring, endogenous insulin was suppressed with somatostatin, while equimolar proportions of porcine insulin and simian C-peptide (2.4 and 6.0 pmol/kg.min) were infused during two consecutive 45-min periods. Insulin reached steady state within 20 min (t1/2 = 4.5 min); however, C-peptide concentrations continued to rise (t1/2 V 12.5 min). The ratio decreased when the peptide infusion was changed to the higher rate and increased when it was stopped, reflecting the more rapid removal of insulin than of C-peptide. Hepatic removal of insulin remained constant during the two infusion periods (average 60% extraction) and never correlated with the changing molar ratios. Hepatic net flux of insulin correlated with the ratio (P less than 0.05) only while plasma insulin concentrations were rising during constant-rate infusion. We therefore conclude that the molar ratio is not a reliable measure of the hepatic removal of insulin during non-steady states of insulin or C-peptide. PMID- 2891471 TI - Criteria for the acceptability of experimental evidence for the enantiomeric composition of xenobiotics and their metabolites. PMID- 2891472 TI - The metabolism of the abortifacient terpene, (R)-(+)-pulegone, to a proximate toxin, menthofuran. AB - (R)-(+)-Pulegone, the major monoterpene component of the abortifacient mint oil, pennyroyal oil, is metabolized by hepatic microsomal monooxygenases of the mouse to a hepatotoxin. The formation of a toxic metabolite is apparently mediated by cytochromes P-450 of the phenobarbital class inasmuch as phenobarbital pretreatment of mice increases, whereas beta-naphthoflavone pretreatment decreases, the extent of hepatic necrosis caused by pulegone. Furthermore, two inhibitors of cytochromes P-450, cobaltous chloride and piperonyl butoxide, block toxicity. An analog of (R)-(+)-pulegone that was labeled with deuterium in the allylic methyl groups was found to be significantly less hepatotoxic than the parent compound. The results indicate that oxidation of an allylic methyl group is required for generation of a hepatotoxic metabolite. Menthofuran was identified as a proximate toxic metabolite of (R)-(+)-pulegone, and investigations with (R)-(+)-pulegone-d6 and 18O2 strongly indicate that menthofuran is formed by a sequence of reactions that involve: 1) oxidation of an allylic methyl group, 2) intramolecular cyclization to form a hemiketal, and 3) dehydration to form the furan. PMID- 2891474 TI - Influence of a purified diet and route of administration on the metabolism and disposition of estradiol in B6C3F1 mice. AB - The metabolism and disposition of [6,7-3H]estradiol ([3H]E2) given by gavage (po) or intravenously (iv) were examined in female B6C3F1 mice fed either the purified AIN-76A (AIN) or cereal-based NIH-07 (NIH) diet for a period of 8 weeks prior to treatment with E2. Initially, 40.6 Ci of [3H]E2 was given iv to each mouse. Subsequently, 45.6 Ci of [3H]E2 was given po to the same mice. Samples of blood, urine, and feces were obtained during a 48-hr period after each dosing. Total radioactivity was determined for each sample. Urine and plasma samples were analyzed by HPLC, and the radiolabeled metabolites were tentatively identified and quantified. Statistical comparisons were made of the effects of diet, route of administration, and interactions among groups. Analysis revealed: 1) greater fecal than urinary excretion of radioactivity regardless of route of administration or diet fed, 2) more radioactivity excreted in the urine of AIN fed than in NIH-fed mice, significantly different only after iv administration (p less than 0.02), and 3) a greater feces:urine ratio of excreted radioactivity following iv than po administration and from NIH-than AIN-fed mice. Metabolite profiles showed: 1) no differences in urine due to route of administration, 2) estriol conjugates dominated urinary metabolites, 3) accumulation of radioactive material in plasma that apparently was tritiated water, with more rapid accumulation of tritiated water after po than iv administration, 4) relatively more plasma estradiol-17-glucuronide, estriol-3-sulfate, and estriol in po- than in iv-treated mice, 5) estradiol-3, 17-sulfate in plasma of iv- but not po treated mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891473 TI - The disposition and metabolism of 2',3'-dideoxycytidine, an in vitro inhibitor of human T-lymphotrophic virus type III infectivity, in mice and monkeys. AB - The pharmacokinetics and metabolism of the anti-human T-lymphotrophic virus type III/lymphadenopathy-associated virus agent 2',3-dideoxycytidine have been examined in BDF1 mice and rhesus monkeys, with ancillary enzyme studies carried out on tissue derived from both the latter species and also from human subjects. For the pharmacokinetic studies, 2',3-dideoxycytidine and its catabolic product 2',3-dideoxyuridine have been separated and measured in plasma, urine, and cerebrospinal fluid by a reverse HPLC method. For metabolic studies, tritium labeled drug (labeled in the 5- and 6-positions of the pyrimidine ring) has been employed, utilizing an ion exchange HPLC analytical method suitable for the separation of the parent nucleoside from its mono-, di-, and triphosphates in cell extracts and in tissue homogenates. The drug is rapidly cleared from plasma in a biphasic manner (terminal t 1/2 in BDF1 mice and rhesus monkeys of 67 min and 109 min, respectively) following an iv bolus dose of 325 mg/m2. This two compartment open model is predictive of plasma concentrations during long term ip infusions in mice. Dideoxycytidine is predominantly excreted in the urine as unchanged parent compound, although a minor urinary metabolite (2,3 dideoxyuridine) is detected in the monkey but not in the mouse. Oral absorption of 2',3'-dideoxycytidine is rapid, with plasma levels approaching those seen after iv administration within 45 min in the mouse. Entry to the central nervous system is also rapid, but the cerebrospinal fluid to plasma AUC ratio after iv administration is only 0.026-0.040 in rhesus monkeys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891475 TI - Distribution of trans-4-hydroxy-2-hexenal and tandem mass spectrometric detection of its urinary mercapturic acid in the rat. AB - The distribution of trans-4-hydroxy-2-hexenal (t-4HH), a pyrrolizidine alkaloid metabolite and a lipid peroxidation product, was studied following the injection of [3H]t-4HH into the hepatic portal vein of male Sprague-Dawley rats. Less than 3% of the tritium label remained in the liver 24 hr after administration with levels in the other major organs correspondingly lower. The majority of recovered radioactivity (77-83%) appeared in the urine with 60-69% appearing within 8 hr after administration. Most of the urinary radioactivity (75%) was recovered in an acidic fraction following acid/base extraction. A tandem mass spectrometry technique using negative ion fast atom bombardment (FAB) ionization in combination with Mass-analyzed Ion Kinetic Energy Spectrometry verified that a C 3 mercapturic acid conjugate of trans-4-hydroxy-2-hexenal was produced as a urinary metabolite. This compound presumably forms via a Michael addition of glutathione at C-3 of t-4HH followed by hydrolysis of glutamate and glycine and acetylation to yield the mercapturic acid. While Michael additions of glutathione to t-4HH-related compounds have been observed in vitro, these results provide in vivo evidence of this mechanism. PMID- 2891476 TI - The role of the liver in mediating the acute toxicity of the pesticide methyl parathion in the mouse. AB - Mouse livers perfused in situ with the pesticide methyl parathion (O,O-dimethyl O P-nitrophenyl phosphorothioate) resulted in the appearance of the toxic metabolite, methyl paraoxon (O,O-dimethyl-O-P-nitrophenyl phosphate), in the effluent perfusate. Mouse whole blood rapidly detoxified methyl paraoxon in vitro, but not at a rate sufficient to prevent transport of at least some of this toxic metabolite from liver to other tissues in vivo. The hepatic disposition and biotransformation of methyl parathion in perfused livers were altered markedly by changes in protein binding of methyl parathion to perfusate, but only slightly by changes in perfusate flow rates that maintained viable livers. Pretreatment of mice with phenobarbital daily for 4 days (80 mg/kg, ip) induced hepatic microsomal activation of methyl parathion to methyl paraoxon in vitro and increased the clearance of methyl parathion by perfused mouse livers. However, in contrast to perfusion of methyl parathion into livers from saline-pretreated mice, perfusion of methyl parathion into livers from phenobarbital-pretreated mice did not lead to the appearance of methyl paraoxon in effluent perfusate. Nevertheless, methyl paraoxon was produced intrahepatically during these perfusions since hepatic cholinesterase activities were depressed compared to livers from phenobarbital-pretreated mice perfused without methyl parathion. Furthermore, phenobarbital pretreatment antagonized the acute toxicity of methyl parathion in vivo in the mouse. These data demonstrate that the net result of the biotransformation of methyl parathion by livers in untreated mice is metabolic activation, whereas the net result by livers of phenobarbital-pretreated mice is detoxification.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891477 TI - Ketorolac tromethamine absorption, distribution, metabolism, excretion, and pharmacokinetics in animals and humans. AB - Ketorolac tromethamine (KT), a potent non-narcotic analgesic, with cyclooxygenase inhibitory activity, was administered (14C-labeled and unlabeled) intravenously (iv), orally (po), and intramuscularly (im) in solution to humans, cynomolgus monkeys, rabbits, rats, and mice. KT was absorbed rapidly (Tmax less than 1.0 hr) and efficiently (greater than 87%) following po and im doses in all species. The plasma half-life of ketorolac (K) ranged from 1.1 hr (rabbits) to 6.0 hr (humans). The protein binding of K ranged from 72.0% (mouse) to 99.2% (humans). Linear pharmacokinetics of K was observed in the mouse after single oral doses of KT ranging from 0.25 to 16 mg/kg. Radioactivity was excreted predominantly into urine, ranging from 78.9% (mouse) to 102% (monkey) following iv doses. The dose was excreted into urine primarily as K conjugates, K, and p-hydroxy-K in humans. The monkey was similar to humans with respect to kinetics, but did not form the p hydroxy metabolite. The rabbit was unusual in that it exhibited substantial presystemic metabolism (50%). The rat excreted a much higher percentage of radioactivity into the feces and formed an additional unidentified metabolite. The most comparable species with respect to humans metabolically was the mouse. The metabolism and excretion of K was similar following iv, po, and im doses within each species studied. PMID- 2891478 TI - Pharmacokinetics and pharmacodynamics of physostigmine in the rat after intravenous administration. AB - The time course of physostigmine (Phy) and metabolites in plasma, brain, and muscle, the inhibition of butyrylcholinesterase (BuChE) in plasma, and cholinesterase (ChE) activity in brain and muscle were studied in rat after iv bolus administration of 3H-Phy (100 micrograms/kg). The semilogarithmic plot of plasma Phy concentration versus time indicates a biphasic decline. These data were analyzed by nonlinear computer fitting program (PC-NONLIN) using a two compartment open model with bolus input and first order elimination. The pharmacokinetic constants A, B, alpha, beta, AUC, K10 half-life, alpha-half-life, beta-half-life, K10, K12, and K21 were obtained. The alpha-half-life and the beta half-life were 1.31 and 15.01 min, respectively. The apparent volume of distribution was found to be 270 ml. The clearance was 12.43 ml min-1. The half life of Phy in brain was 11 min. The brain to plasma ratio (1.69) peaked at 15 min. Phy is metabolized to eseroline and three other metabolites, M1, M2, and M3. The distribution studies showed that the radioactivity per g of tissue was highest in kidney and liver, whereas the percentage of the administered dose in terms of radioactivity was maximum in muscle followed by liver. The maximum inhibition of BuChE (52%) correlates with the highest Phy concentration (84.6 ng/ml) in plasma at 2 min and 70% of the enzymic activity recovered by 45 min. The maximum inhibition of ChE (63%) in the brain correlates with the highest Phy concentration (128 ng/g) at 3 min, and 85% of the enzymic activity was recovered within an hour.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891479 TI - Oxidation of the alcohol dehydrogenase inhibitor pyrazole to 4-hydroxypyrazole by microsomes. Effect of cytochrome P-450 inducing agents. AB - Pyrazole and its analogues are widely used to inhibit alcohol dehydrogenase and to block the metabolism of ethanol. Experiments were conducted to demonstrate that pyrazole is oxidized to 4-hydroxypyrazole by isolated rat liver microsomes. A HPLC procedure employing UV and electrochemical detection was developed for the separation and quantitation of 4-hydroxypyrazole. Pyrazole metabolism was NADPH dependent, sensitive to inhibition by carbon monoxide, and was depressed in the presence of other substrates such as aniline or ethanol. Prior treatment of rats with either pyrazole or 4-methylpyrazole resulted in an increase in pyrazole oxidation to 4-hydroxypyrazole by microsomes. Increases were observed when rates were expressed either per mg of protein or per nmol of P-450. Microsomes from pyrazole- and 4-methylpyrazole-treated rats had Km values for pyrazole of about 0.29 and 0.14 mM, respectively, and Vmax values of about 0.5 and 0.7 nmol of 4 hydroxypyrazole per min per mg of protein, respectively. Chronic consumption of ethanol for 24 days resulted in an increase in pyrazole oxidation (per mg of protein and per nmol of P-450) as compared to pair-fed controls. By contrast, phenobarbital treatment lowered the rate of production of 4-hydroxypyrazole. Treatment with 3-methylcholanthrene resulted in an increase in pyrazole oxidation when rates were expressed per mg of protein, but not per nmol of P-450. These results show that pyrazole is oxidized to 4-hydroxypyrazole by microsomes in a P 450-dependent manner and that this metabolism can be increased by certain inducers, e.g. pyrazole, 4-methylpyrazole, and chronic ethanol treatment. PMID- 2891480 TI - Disposition of the monoclonal antibody-vinca alkaloid conjugate, KS1/4-DAVLB (LY256787), in Fischer 344 rats and rhesus monkeys. AB - The conjugate, KS1/4-DAVLB, of the murine monoclonal antibody KS1/4 with the vinca alkaloid 4-desacetylvinblastine (DAVLB) was administered intravenously to rats and monkeys. Terminal plasma half-life (t1/2) values were measured as radioequivalents and as functionally immunoreactive antibody conjugate after dosing with KS1/4-[3H]DAVLB. The t1/2 values, determined radiometrically, were 145 hr and 62 hr in male rats after 10 and 100 mg/kg doses and 92 hr and 90 hr in male and female monkeys after a 40 mg/kg dose. Comparable results were obtained when the functionally immunoreactive conjugate concentrations were determined by an enzyme-linked immunosorbent assay technique. The ratio of 35S:3H in the plasma after dosing rats with 100 mg/kg [35S]KS 1/4-[3H]DAVLB remained reasonably constant during 336 hr. Less than 1% of the total vinca alkaloid equivalents present in the plasma at any time could be extracted as free vinca species; the major vinca alkaloid metabolities present at early time points were hemisuccinate derivatives of DAVLB, whereas, at later times, DAVLB and its N-oxide were equally as concentrated. The major pathway of elimination was fecal with about one-half of the administered radioactivity cleared in 150-250 hr. After dosing with [35S]KS 1/4-[3H]DAVLB, the ratio of 35S:3H radioactivity in the bile was substantially less than that in the plasma. Evaluation of radioactivity eluted from the bile by size-exclusion HPLC showed that almost all of the tritium was associated with material of lower molecular weight than that of KS 1/4 DAVLB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891481 TI - Mechanism-based inhibition of cytochrome P-450 by heterocyclic analogues of phencyclidine. AB - Three homologues of 1-(1-phenylcyclohexyl)piperidine (PCP) containing the five-, six-, and seven-membered heterocyclic ring (1-(1-phenylcyclohexyl)pyrrolidine (PCPY), PCP, 1-(1-phenylcyclohexyl)hexamethyleneimine (PCHMI) were preincubated with microsomes from phenobarbital-induced rabbit liver. The microsomes were then diluted, an additional charge of NADPH was added, and N-demethylation of benzphetamine was determined. Preincubation of the microsomes with the analogues lowered P-450-dependent N-demethylation by a process that was NADPH-dependent, reduced CO binding to microsomes, and followed pseudo-first order kinetics. The relative rates of inactivation, PCP greater than or equal to PCPY greater than PCHMI, agreed with the order of inhibition of CO binding to reduced microsomes. This mechanism-based inhibition was not observed with phenylcyclohexylamine, indicating that the substituted nitrogen is necessary. The substituted nitrogen must also be part of a heterocyclic ring since the diethylamino analogue of PCP did not exhibit the same type of inhibition a heterocyclic ring is involved. These trends correlated with the expected relative stabilities of the cyclic form of the carbinolamine suggesting that the inhibitory species was formed from the closed ring isomer. PMID- 2891482 TI - Relationship between the murine Ah phenotype and the hepatic uptake and metabolism of 2,3,7,8-tetrachlorodibenzo-p-dioxin. AB - The influence of the Ah locus on the hepatic uptake and metabolism of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) was studied using isolated hepatocytes from Ah responsive C57BL/6J (C57) and nonresponsive DBA/2J (DBA) mice. Hepatocytes from control and TCDD-pretreated C57 and DBA mice were incubated with purified [14C] TCDD (2.2 microM) for 8 hr in the metabolism studies or 2 hr in the uptake studies. Mice were pretreated 7 days prior to hepatocyte isolation with TCDD at doses that maximally induce aryl hydrocarbon hydroxylase activity (C57: 3 micrograms/kg, ip; DBA: 30 micrograms/kg, ip) or at doses approaching the LD50 value (C57: 150 micrograms/kg, ip; DBA: 600 micrograms/kg, ip). Hepatocytes isolated from untreated C57 and DBA mice had similar uptake of [14C]TCDD, and, at all doses, TCDD pretreatment increased [14C]TCDD uptake. The rates of hepatic TCDD metabolism over the first 2 hr of incubation were similar for control C57 and DBA mice, although some qualitative differences in metabolites were detected by HPLC. TCDD pretreatment at doses of 3 and 30 micrograms/kg for C57 and DBA mice, respectively, produced no detectable quantitative or qualitative changes in TCDD metabolism, despite increases in cytochrome P-450 content, 7-ethoxyresorufin O-deethylase (EROD) activity, and benzo[a]pyrene (BaP) metabolism. Pretreatment of C57 and DBA mice with the respective LD50 doses of TCDD decreased the rate of TCDD metabolism by hepatocytes, although cytochrome P-450 content, EROD activity, and BaP metabolism were increased. These results suggest that the uptake and the rate of hepatic metabolism of TCDD do not correlate with genetic differences at the murine Ah locus. PMID- 2891483 TI - The in vitro activity, radioimmunoassay cross-reactivity, and molecular weight of thirteen rabbit cyclosporine metabolites. AB - Thirteen metabolites of cyclosporine were isolated from the bile of rabbits receiving intravenous cyclosporine. The molecular weights of these metabolites were determined by fast atom bombardment mass spectrometry. These molecular weights were consistent with hydroxylated, N-demethylated, and carboxylated metabolites of cyclosporine as described previously. The in vitro activities of the metabolites were established using mitogen-stimulated lymphocyte proliferation assays. Only the two monohydroxylated metabolites were found to have significant activity, this being between 5 and 10% of that of the parent drug. The metabolites were also compared with cyclosporine in two commercial radioimmunoassay kits. The metabolites were found to cross-react with the parent drug in amounts ranging from 20 to 100%, with the least polar metabolites cross reacting the most strongly. It is concluded that the cross-reacting metabolites measured by the presently available radioimmunoassays for cyclosporine probably do not represent significant additional immunosuppressive activity in vivo. PMID- 2891485 TI - The disposition of N-(4,6-dimethyl-2-pyrimidinyl)benzene[U-14C]sulfonamide in the rat. AB - Rats given a single oral dose of N-(4,6-dimethyl-2-pyrimidinyl)benzene[U 14C]sulfonamide (14C-DAS) excreted 64.2% of the 14C in the urine and 22.4% in the feces within 96 hr. Compounds accounting for 86% of the 14C in the 0-24-hr urine were isolated by a variety of chromatographic techniques and identified by IR, NMR, and MS analysis. Approximately 4% of the 14C in the urine was the parent compound. The structures of 14C-metabolites in the urine indicated that 14C-DAS was metabolized by at least three pathways which included: 1) hydroxylation and glucuronic acid conjugation at the 4-position of the benzene ring; 2) hydroxylation, and sulfate ester and glucuronic acid conjugation at the 5 position on the heterocyclic ring; and 3) hydroxylation and glucuronic acid conjugation of one methyl group on the heterocyclic ring. PMID- 2891484 TI - In vivo and in vitro renal metabolism and excretion of benzoic acid by a marine teleost, the southern flounder. AB - In mammals, benzoic acid is primarily metabolized to its glycine conjugate, hippuric acid, which is readily excreted via the renal organic anion transport system. Teleost fish have not been shown to make glycine conjugates of carboxylic acids. Therefore, metabolism, excretion, and renal transport of benzoic acid were examined in the southern flounder, Paralichthys lethostigma. Excretion of injected [14C]benzoic acid was slow (10% of the administrated dose/day) and followed zero order kinetics. More than 95% of the excreted label was a single metabolite which was shown by hydrolysis and TLC to be benzoyltaurine. Isolated renal tubules and both hepatic and renal mitochondria produced benzoyltaurine in vitro. Excretion of benzoic acid and benzoyltaurine were not limited by plasma binding (less than 5% bound). To examine whether the slow excretion reflected renal transport, the transport of 100 microM benzoic acid, benzoyltaurine, and hippuric acid were determined in isolated renal tubules. All three compounds were accumulated via a probenecid- and cyanide-sensitive mechanism. Probenecid sensitive uptake at 60 min of hippuric acid (436 nmol/mg) was greater than that of benzoyltaurine (164 nmol/mg) and both exceeded uptake of benzoic acid (63 nmol/mg). The same pattern was seen at 10 microM, except that tissue:medium ratios were even greater, indicating at least partial saturation of transport at 100 microM. Thus, the slow excretion of benzoic acid by these flounder was due to a combination of factors, including slow metabolism of benzoic acid to benzoyltaurine, saturation of the transport of benzoyltaurine, and low affinity of secretory transport for benzoic acid and benzoyltaurine, relative to hippuric acid, the mammalian metabolite. PMID- 2891486 TI - The development of hepatic drug-metabolizing enzyme activity in the neonatal calf and its effect on drug disposition. AB - Mixed function oxidase and UDP-glucuronyltransferase activity was measured in liver microsomal preparations from 1-, 7-, and 42-day-old, male, Holstein calves. Liver samples were obtained by a surgical biopsy procedure that allowed for multiple samples to be taken from a single individual. Microsomal protein content doubled between 7 and 42 days of age and reached adult levels during this time. Cytochrome P-450 content increased 2-fold during the first week and remained constant thereafter. NADPH-cytochrome c reductase activity doubled during the first week, but then returned to its initial level by 42 days of age. UDP glucuronyltransferase activity was well developed at 1 day of age and reached adult levels by 7 days of age. Mixed function oxidase activity was less well developed; activities at 1 day of age were only 17-50% of those at 42 days of age for O-deethylation, O- and N-demethylation, and aryl hydrocarbon hydroxylation. Development of hepatic drug-metabolizing activity was discussed in relation to the age-related increase in the rate of elimination of the antibacterial compound trimethoprim. PMID- 2891487 TI - The metabolism of 7-ethylbenz[a]anthracene by rat liver microsomal preparations. AB - 7-Ethylbenz[a]anthracene (7-EBA) is a much weaker carcinogen than the 7-methyl analogue (7-MBA), and this difference may be based upon differences in the pathways by which the two compounds are metabolized and activated. In the present work, 7-EBA and the related 7 alpha- and 7 beta-hydroxyethyl derivatives (7-OHEBA and 7-beta-OHEBA) have been incubated with microsomes prepared from the livers of rats pretreated with 3-methylcholanthrene, the metabolites were extracted and purified by TLC, and the products present in the dihydrodiol band were examined by analytical HPLC. Metabolites were identified by comparison with authentic reference standards and by their chromatographic, UV, fluorescence, mass, and NMR spectral characteristics. The 7-EBA metabolites included the 1,2- 3,4, 5,6- 8,9- and 10,11-dihydrodiols, the 3,4- 8,9- and 10,11-dihydrodiols of 7-alpha-OHEBA, and three phenolic dihydrodiols that were not completely characterized. No 7-beta OHEBA derivatives were detected as metabolites of 7-EBA. The results obtained so far have not revealed any qualitative differences in the routes by which 7-EBA and 7-MBA are metabolized in rat liver microsomal preparations. PMID- 2891488 TI - Physiologically based pharmacokinetic model for the renal clearance of salicyluric acid and the interaction with phenolsulfonphthalein in the dog. AB - Plasma kinetics and renal excretion of salicyluric acid (SUA, 0.8 g) administered iv, with and without concomitant administration of phenolsulfonphthalein (PSP), were studied in the beagle dog. Pharmacokinetic analysis revealed that tubular secretion is the predominant route of excretion, and that secretion is inhibited by PSP. A physiologically based kidney model is presented comprising all the functional characteristics of the kidney that determine the excretion of SUA, i.e. renal plasma flow, urine flow, nonlinear protein binding, glomerular filtration, tubular secretion, and tubular accumulation. The model enabled an accurate description and analysis of the measured plasma levels and renal excretion rates. The interaction with PSP could be adequately described with the model by noncompetitive inhibition of the carrier-mediated uptake of SUA into the tubular cells. Furthermore, a small but significant reduction in nonrenal SUA clearance was observed. Model calculations showed that, in the control experiments, tubular secretion was accompanied by a pronounced accumulation of SUA within the cells, which was clearly diminished in the presence of PSP. The predicted accumulation ratios were in good agreement with previously reported in vitro values. PMID- 2891489 TI - Bioactivation of tetrachloroethylene. Role of glutathione S-transferase-catalyzed conjugation versus cytochrome P-450-dependent phospholipid alkylation. AB - The metabolism of [14C]tetrachloroethylene (Tetra) and its metabolite S-(1,2,2 trichlorovinyl)-L-cysteine (TCVC) was investigated with in vitro systems to substantiate metabolic pathways of Tetra deduced from in vivo experiments. In the presence of NADPH, rat hepatic microsomal fractions metabolized Tetra to soluble metabolites, which were identified as trichloroacetic acid and oxalic acid by gas chromatography/mass spectroscopy and a metabolite largely bound to microsomal macromolecules. The majority of the alkylated macromolecules were identified as N trichloroacetylated phospholipids by high performance liquid chromatography and GC/MS. When Tetra was incubated with hepatic microsomes and cytosol in the presence of 10 mM glutathione, but in the absence of NADPH, the formation of a polar metabolite other than trichloroacetic acid and oxalic acid was observed. This metabolite was identified, after hydrolysis to the corresponding cysteine conjugate, as S-(1,2,2-trichlorovinyl)-glutathione (TCVG). Microsomal GSH S transferases catalyzed TCVG formation more efficiently than cytosolic GSH S transferases; the competitive substrate 1-chloro-2,4-dinitrobenzene inhibited TCVG formation. In the presence of both NADPH and GSH, TCVG formation in microsomes was decreased, indicating that oxidative metabolism and GSH conjugation of Tetra are competitive reactions. The Tetra metabolite TCVC was cleaved by bacterial cysteine conjugate b-lyase to dichloroacetic acid and pyruvate. The obtained results substantiate the postulated pathways of Tetra biotransformation and demonstrate that both oxidative and conjugative reactions occur in hepatic Tetra metabolism. Phospholipid alkylation, which occurs during oxidative metabolism, may be a deactivation reaction, whereas TCVG formation, renal metabolism to TCVC, and cleavage of TCVC by b-lyase under formation of mutagenic intermediates may contribute to the nephrocarcinogenic effect of Tetra. PMID- 2891491 TI - Direct detection of new flucytosine metabolites in human biofluids by 19F nuclear magnetic resonance. AB - 19F nuclear magnetic resonance was used for the analysis of flucytosine (FC; 5 fluorocytosine) metabolites in biological fluids of a patient with cryptococcal meningitis who was intravenously injected with this drug at a daily dose of 7.5 g (2.5 g at 8-hr intervals). This method allows a direct, simultaneous, and quantitative determination of all the fluorinated metabolites of FC, in the range of sensitivity allowed by the spectrometer (sensitivity threshold, 0.01 mM). In urine, in addition to the already reported metabolites [unmetabolized FC and alpha-fluoro-beta-alanine (FBAL)], three new metabolites were identified: a glucuronide of FC (GLFC), 6-hydroxy-5-fluorocytosine (60HFC), and fluoride ion F . The same metabolites (except F-) were found in plasma. In cerebrospinal fluid, only unchanged FC and GLFC were observed. The total urinary excretion during an 8 hr period between two injections of FC was 100.4% of the injected dose. Unchanged FC was the major excretory product accounting for 96.1% of the total. GLFC and 6OHFC made up, respectively, 2.7% and 1.2% of the excreted metabolites. The proportions of F- and FBAL were very low, respectively, 0.3% and 0.1% of the excreted metabolites. The global urinary excretion over a 24-hr period was 102% of the injected dose. The proportions of metabolites were very close to those obtained for the 8-hr period. In plasma, the proportions of metabolites were analogous to those determined in urine. In cerebrospinal fluid, GLFC represents 1% of the fluorinated metabolites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891490 TI - Glucuronidation in vitro and in vivo. Comparison of intestinal and hepatic conjugation of morphine, naloxone, and buprenorphine. AB - The glucuronidation of morphine, naloxone, and buprenorphine by the liver and intestine has been assessed both in vitro and in vivo in the rat. Using microsomes, Vmax/Km ratios were estimated as measures of intrinsic enzyme activity, and a wide range of ratios were obtained (500-fold). The ratio for the intestine was consistently less than for the liver, and the rank order of activities within each tissue was morphine less than naloxone less than buprenorphine. Using various routes of administration, plasma concentration-time profiles for each compound were determined and used to estimate hepatic and intestinal extraction ratios. These extraction ratios were dose-independent and more substantial for the liver than the intestine. For each tissue, buprenorphine and naloxone showed similar extraction, whereas morphine was less. Plasma binding and blood/plasma concentration ratios were determined, and perfusion models were used to calculate intrinsic clearance. This in vivo parameter of enzyme activity showed a wide range (200-fold), comparable to the spread of microsomal Vmax/Km ratios. Although the in vivo parameters consistently gave measures 10- to 30-fold higher than the in vitro parameters, the rank order was identical for the two sets. These data suggest that a comparative approach to correlate in vitro and in vivo data has advantages over the use of absolute drug characteristics. PMID- 2891492 TI - Influence of gonadal hormones upon rat hepatic acetaminophen sulfotransferases. PMID- 2891493 TI - Pharmacokinetics of acetaminophen, vancomycin, and antipyrine in the Hanford miniature swine. PMID- 2891494 TI - Effect of cyclosporine on hepatic oxidative and conjugative metabolism in rats. PMID- 2891495 TI - [Treatment of esophageal varices bleeding with vasoactive substances]. PMID- 2891496 TI - [Anti-asthmatic agents in pregnancy]. PMID- 2891497 TI - The P300 metric in schizophrenia: effects of probability and modality. PMID- 2891498 TI - [GABA receptors in the central nervous system. Biochemical and pharmacological aspects]. PMID- 2891499 TI - [GABA and anxiety]. PMID- 2891500 TI - Familial multiple endocrine neoplasia type I: a new look at pathophysiology. PMID- 2891501 TI - The role of the multichain IL-2 receptor complex in the control of normal and malignant T-cell proliferation. AB - Antigen-induced activation of resting T-cells induces the synthesis of interleukin-2 (IL-2), as well as the expression of specific cell surface receptors for this lymphokine. There are at least two forms of the cellular receptors for IL-2, one with a very high affinity and the other with a lower affinity. We have identified two IL-2 binding peptides, a 55-kd peptide reactive with the anti-Tac monoclonal antibody, and a novel 75-kd non-Tac IL-2 binding peptide. Cell lines bearing either the p55, Tac, or the p75 peptide alone manifested low-affinity IL-2 binding, whereas cell lines bearing both peptides manifested both high- and low-affinity receptors. Fusion of cell membranes from low-affinity IL-2 binding cells bearing the Tac peptide alone with membranes from a cell line bearing the p75 peptide alone generates hybrid membranes bearing high affinity receptors. We propose a multichain model for the high-affinity IL-2 receptor in which both the Tac and the p75 IL-2 binding peptides are associated in a receptor complex. In contrast to resting T-cells, human T-cell lymphotropic virus I-associated adult T-cell leukemia cells constitutively express large numbers of IL-2 receptors. Because IL-2 receptors are present on the malignant T cells but not on normal resting cells, clinical trials have been initiated in which patients with adult T-cell leukemia are being treated with either unmodified or toxin-conjugated forms of anti-Tac monoclonal antibody directed toward this growth factor receptor. PMID- 2891502 TI - Specific expression of the Hox 1.3 homeo box gene in murine embryonic structures originating from or induced by the mesoderm. AB - The murine Hox 1.3 homeo box-containing gene is expressed largely in mesoderm derived or mesoderm-induced embryonal structures, as evidenced by in situ hybridization techniques. Expression is spatially limited to the thoracic region, specifically to components of segmental origin such as embryonal ribs and vertebrae and their precursors such as the equivalent sclerotomes, somites and somatic condensations. In addition, expression can be found in parts of embryonal lung, stomach tissue, gut and kidney, tissues whose formation is based on induction of region-specific mesoderm, as well as in some ectoderm-derived tissues. The expression is temporally controlled for the transcripts and can only be detected while the thoracic structures are being formed (days 8-13), but not at day 18 of gestation when the embryo is mature. These data suggest a role of Hox 1.3 gene in the generation of tissues derived from or induced by the embryonal mesoderm. PMID- 2891504 TI - Ectopic pituitary and hypothalamic hormone syndromes. AB - The pathophysiology and diagnosis of ectopic hormone syndromes are discussed, and a classification of hypothalamic and pituitary ectopic syndromes is provided. Ectopic hypothalamic syndromes resulting from tumor elaboration of GRH, GnRH, CRF, and SRIF and ectopic pituitary hormone hypersecretion of GH, PRL, and TSH are reviewed comprehensively. A practical approach to the clinical work-up and management of these newly described disorders is provided. PMID- 2891503 TI - Hox-1.6: a mouse homeo-box-containing gene member of the Hox-1 complex. AB - Hox-1.6, a mouse homeo-box-containing gene member of the Hox-1 complex, is described. The Hox-1.6 homeo-box shows more divergence than the other members of the complex with the Drosophila Antennapedia-like homeo-box class. This previously undescribed gene was studied with respect to its transcription pattern and was found to be expressed during mouse fetal development in an intestine specific manner in adults, and in tumours or cell types exhibiting early endodermal-like differentiation. The study of embryonic partial Hox-1.6 cDNA clones revealed structural features common to other Drosophila and vertebrate homeo-box-containing genes, but also indicated that Hox-1.6 transcripts might display splicing patterns more complex than those known for other vertebrate homeo-genes. One of these cDNA clones contains a rather short open reading frame which would encode a protein of approximately 14.5 kd. The use of this clone as a probe for S1 nuclease mapping confirmed that different Hox-1.6 transcripts were present both in embryonic total RNA and in embryonal carcinoma cell cytoplasmic RNA. These various transcripts are probably generated by an alternative splicing mechanism and may thus encode a set of related proteins. PMID- 2891505 TI - A recombinagenic effect of strychnine in Salmonella typhimurium. AB - The aroC321 allele in Salmonella typhimurium permits a positive selection for genetic duplications. Bacteria that contain a large genetic duplication are detected as tryptophan prototrophs in aroC321 strains and occur at a spontaneous frequency greater than 1/10(4) cells plated on the selection medium. Duplications originate by a recombinational mechanism, and the induction of duplications by chemicals or radiation may therefore be considered to be a recombinagenic effect. We have found that strychnine is a potent recombinagen in this system; it causes a dose-dependent increase in the frequency of genetic duplications, and very high frequencies of duplications are recovered at high doses. In contrast, brucine, the 2,3-dimethoxy derivative of strychnine, caused no increase in duplication frequencies under the identical conditions. PMID- 2891506 TI - Mitochondrial precursor proteins are imported through a hydrophilic membrane environment. AB - We have analyzed how translocation intermediates of imported mitochondrial precursor proteins, which span contact sites, interact with the mitochondrial membranes. F1-ATPase subunit beta (F1 beta) was trapped at contact sites by importing it into Neurospora mitochondria in the presence of low levels of nucleoside triphosphates. This F1 beta translocation intermediate could be extracted from the membranes by treatment with protein denaturants such as alkaline pH or urea. By performing import at low temperatures, the ADP/ATP carrier was accumulated in contact sites of Neurospora mitochondria and cytochrome b2 in contact sites of yeast mitochondria. These translocation intermediates were also extractable from the membranes at alkaline pH. Thus, translocation of precursor proteins across mitochondrial membranes seems to occur through an environment which is accessible to aqueous perturbants. We propose that proteinaceous structures are essential components of a translocation apparatus present in contact sites. PMID- 2891507 TI - Liquid crystal thermography in the localization of undescended testicles. AB - Liquid crystal thermography (LCT) for the localization of undescended testicles was performed in 28 patients, in 21 of whom ultrasonography (US) was also performed: Among the 21 operated cases, LCT correctly localized the testicles in 19, and US in 18 cases. LCT may be used in screening for undescended testicles. PMID- 2891508 TI - Biosynthesis of intestinal microvillar proteins. Forskolin reduces surface expression of aminopeptidase N. AB - The effect of forskolin on the biosynthesis and intracellular transport of pig intestinal aminopeptidase N (EC 3.4.11.2) was studied in organ cultured mucosal explants. The drug which activates adenylate cyclase and hence the cAMP-dependent glycogenolytic pathway did not affect the explant content nor microvillar enrichment of the enzyme. Forskolin, however, caused a decrease in the microvillar expression of aminopeptidase N which developed in a time-dependent manner from about 40% by 80 min to 80% by 4 h of labeling. The intracellular pool size of the transient, high mannose glycosylated form of aminopeptidase N was unaffected by forskolin, indicating a normal synthesis in the rough endoplasmic reticulum. The decrease in surface expression is therefore caused by an induced posttranslational degradation of the enzyme, most likely taking place in the Golgi complex. The degradatory effect on newly synthesized aminopeptidase N was not accompanied by any morphological alterations of the enterocyte; in particular, the microvillar membrane appeared entirely unaffected by forskolin. The results obtained provide evidence for the existence of a posttranslational mechanism, whereby a polarized cell is capable of regulating its expression of apical proteins. PMID- 2891510 TI - International Symposium on Pediatric and Surgical Andrology: Cryptorchidism. March 26-27, 1987, Basle, Switzerland. On the occasion of the 125th anniversary of the Children's Hospital Basle. PMID- 2891509 TI - Molecular biology of phenylketonuria. PMID- 2891511 TI - Magnetic resonance imaging of the cryptorchid testis. AB - Magnetic resonance imaging was used to evaluate seven patients with undescended testes. In six patients the presence or absence of testicular tissue was predicted correctly prior to surgery. Spermatic cord structures, if present, were accurately visualized in all patients. PMID- 2891512 TI - Relevance of urinary gonadotrophins. AB - The assay of urinary LH and FSH in first morning void urine can be used for the differential diagnosis between anorchism and bilateral cryptorchidism with impalpable testes. Furthermore, levels of urinary LH and FSH excretion and their response to intranasal stimulation with LH-RH prove helpful in the follow-up of patients under hormonal treatment, i.e. prolonged stimulation in hypogonadotrophic hypogonadism or suppression by an LH-RH analogue, for instance in precocious puberty. By increasing the sensitivity of the assay, the value of urinary gonadotrophins for the differential diagnosis and survey of hormonal treatment in very young children can be examined, and investigations of this kind are currently taking place. The method used obviously cannot assess the bioactivity of the excreted hormone, nor can it depict the pulsatility of gonadotrophin secretion. PMID- 2891513 TI - The pituitary-gonadal axis in cryptorchid infants and children. AB - We have attempted to document in cryptorchid children that there is an LH deficiency and a secondary deficiency of testosterone. We have shown a diminished LH peak after LH-RH in cryptorchid versus normal infants (P less than 0.05). The postnatal surge of testosterone is significantly low (P less than 0.001) in permanent cryptorchids versus infants with secondary testicular descent, whose levels are similar to those in controls. In permanent cryptorchids during the same period (0-4 months), LH and testosterone levels were significantly lower (P less than 0.01 and P less than 0.05 respectively) than in infants with secondary descent, and the levels of testosterone and LH were correlated in both populations. In children, a low basal level of LH was observed at pubertal stage P2, and LH peak after LH-RH was significantly reduced at stages P1 and P2 (P less than 0.01 and P less than 0.05 respectively). The post-stimulatory levels of testosterone after hCG were reduced at the same stages (P less than 0.01, P less than 0,05), and the two levels were correlated (P less than 0.01). No differences are seen for LH and testosterone afterwards. It has been possible to show by immunofluorescence on pituitary cells the occurrence of antigonadotropin cell antibodies (AGCA) in more than 50% of our patients, with no relation to age and no correlations between endocrinological data and the presence or absence of AGCA. The relatively low success rate of hCG treatment, mainly in young children, and of GnRH irrespective of the regimen of treatment, does not exclude the role of primary LH deficiency in cryptorchidism. PMID- 2891514 TI - Fertility in cryptorchidism. An overview in 1987. AB - Both hormonal and surgical treatment of cryptorchidism have undergone an evolution, resulting in improved management of this condition. Current factors influencing fertility are reviewed, with regard to present and future treatment. PMID- 2891515 TI - Germ cell counts in semithin sections of biopsies of 115 unilaterally cryptorchid testes. The experience from the Children's Hospital of Philadelphia. AB - One hundred and fifteen biopsies from unilateral cryptorchid prepubertal patients were embedded in Epon. Semithin sections were examined by light microscope and the germ cell count per tubule was calculated. The mean number of germ cells was normal from birth to 12 months of age and dropped below the lower limits of normal between 1 and 2 years. Germ cell counts rose considerably during the 18 months observation period with the highest counts occurring in the last 6 months. Variability in the clinical diagnosis of cryptorchidism or inherent heterogeneity in the testicular histology of cryptorchidism are possible explanations. PMID- 2891516 TI - The epididymis and testicular descent. AB - The surgical findings in 197 consecutive cases of cryptorchidism demonstrate a 63% incidence of unfurled epididymides. This anomaly was more prevalent with bilateral cryptorchidism. The associated hernias, testicular and epididymal appendages were also more common in the unfurled epididymides cases, particularly in those that were bilateral. PMID- 2891517 TI - Therapeutic results in cryptorchidism after combination therapy with LH-RH nasal spray and hCG. AB - Seventy-two boys with 81 cryptorchid testes were treated with combined LH-RH nasal spray and hCG in the period between 1983 and 1985. Cryptocur (LH-RH) was applied as nasal spray at a dose of 1.2 mg daily over a period of 14 days. In all of the patients, hCG treatment was carried out subsequently according to the WHO guidelines with five intramuscular injections at 2-day intervals. Primary treatment results considerably improved using the regimen. The rate of complete descent was 86.4% at the end of therapy and later dropped to 70.6% after 2 years follow-up. These results support the experience of Hadziselimovic et al. with this combined treatment. PMID- 2891518 TI - LH-RH nasal spray treatment for cryptorchidism. A double-blind, placebo controlled study. AB - A double-blind, placebo-controlled study of the efficacy of LH-RH nasal spray in treatment of cryptorchidism involving 252 prepuberal boys with 301 undescended testes, showed a success rate of 9% (14 testes) for LH-RH and 8% (10 testes) for placebo. Including a subsequent open study and a second course of LH-RH as required, the rate for LH-RH rose to 18% (48 testes). The follow-up period saw late descent in another 5% (14 testes), in a few cases coinciding with the onset of puberty. Retrospective evaluation revealed a previous scrotal position of the testes for 43% of the boys with success of treatment and even for 17% of the boys with failure of treatment. In many of these cases surgery revealed an anatomical anomaly that might have caused testicular ascent. Hormonal evaluation revealed no abnormalities in cryptorchid boys compared with control subjects, nor was there a divergence in values before and after treatment. The lower the pretreatment testicular position, the better the rate of success. PMID- 2891519 TI - Results of combined hormonal and surgical treatment for undescended testis in boys under 3 years of age. A randomized study. AB - The effects of hormonal treatment (LH-RH, LH-RH plus hCG) on undescended testis were studied on 42 testicles in 37 boys under 3 years of age. Descensus was achieved primarily in 40% but eight testicles reascended. A new course of hCG resulted in descensus in three cases. Altogether, therefore, full descensus could be achieved in 29% of cases with hormonal treatment. Hormonal treatment is recommended before surgery. PMID- 2891520 TI - Intranasal LH-RH treatment of cryptorchidism. A clinical trial and 5 years follow up. AB - The effect of intranasal LH-RH on cryptorchidism was investigated in 45 prepubertal boys with 68 undescended testes. A daily dose of 1.2 mg LH-RH was given for 4 weeks. A total of 16 testes (24%) descended. Follow-up examination 5 years later showed that relapse had occurred in two cases. Fifty-two testes did not descend during the LH-RH treatment. However, seven of these testes descended spontaneously during puberty. So far surgical treatment has been carried out in 39 of the remaining 45 testes. Anatomical anomalies (ectopic position of the testis, open processus vaginalis, abnormal epididymis) explained the failure of LH-RH to cause descent in the majority of the surgically treated cases. PMID- 2891521 TI - Intranasal LH-RH for cryptorchidism: response to initial treatment and to treatment after relapse. AB - Fifty-three prepubertal boys with unilateral (n = 38) or bilateral (n = 15) cryptorchidism were treated for 4 weeks with synthetic LH-RH (Cryptocur, Hoechst) 1.2 mg daily, divided into 3 X 400 micrograms and administered intranasally. Complete descent was observed in 54% of testes--37% in the boys with unilateral cryptorchidism and 77% in the boys with bilateral cryptorchidism. Follow-up examination 6 months after therapy showed relapse in 30%, and a second therapeutic trial with intranasal LH-RH was effective in all these cases. Treatment of cryptorchidism with intranasal synthetic LH-RH, 3 X 400 micrograms/day, seems to be very effective, painless and without major side effects. However, follow-up is mandatory. PMID- 2891522 TI - LH-RH treatment for cryptorchidism. Randomized study and 10-year follow-up results. AB - A randomized study (LH-RH treatment or surgery) of 60 cryptorchid children between 2 and 9 years of age was performed. Testicular biopsy obtained in all patients undergoing orchiopexy showed histological changes compatible with cryptorchidism. Only maldescended and non-retractile testes were treated. LH-RH treatment was successful in 59% of the patients. Ten years later, 52% of testes remained descended. Thus LH-RH treatment is effective in achieving descent of true cryptorchid testes. PMID- 2891523 TI - Management of the intra-abdominal testis. AB - A survey was made of 30 pediatric urologists for their current practice. Localization, important for operative approach, is done by venography and arteriography; ultrasonography, computed tomography and magnetic resonance imaging; and laparoscopy, the last most often immediately before operation. The preferred operation is the long-loop vas orchiopexy; two-stage orchiopexy and microsurgical auto-transplantation are alternatives. PMID- 2891524 TI - Microvascular orchiopexy. AB - In the period between 1981 and 1986, 22 microvascular testicular autotransplantations were performed on 18 patients at the Royal Manchester Children's Hospital. The preoperative assessment, the operative technique, and the follow-up results are discussed. Of 22 transplanted testes, four (18.2%) became partially or totally atrophic. The early results are very encouraging; however, only long-term postpubertal follow-up regarding both fertility and malignancy can reveal the real value of this operation. PMID- 2891525 TI - Primary and secondary testicular atrophy. AB - 1. (a) Primary and secondary testicular atrophy is caused by ischaemia, most frequently after intrauterine and prepuberal testicular torsion. (b) After standard orchiopexy, and especially after orchiopexy in high undescended testis, secondary testicular atrophy is frequent. (c) The histological condition of a cryptorchid testis does not predict atrophy. Immediate detorsion and/or prophylactic fixation as well as subtle technique in orchiopexy are essential. 2. Sympathetic orchiopathy of a unilateral atrophic testis was not proven in cryptorchidism and testicular torsion. There is considerable evidence of primary bilateral disease. 3. Testicular atrophy as an aetiological factor in the development of testicular tumor remains open to debate. PMID- 2891526 TI - Treatment of cryptorchidism with low doses of buserelin over a 6-months period. AB - In a collaborative study, 48 prepubertal boys with undescended testes ranging in age from 15 months to 11 years were treated with low-dose intranasal buserelin following an every-other-day programme for a period of 6 months. Urinary LH, FSH, and testosterone were not altered during the treatment period. Boys over 7 years of age experienced a slight but significant rise in testosterone at the end of treatment. Testicular descent was achieved in only 17% of boys. In the remainder, bilateral testicular biopsies were obtained during orchiopexy. Grouped analysis showed a significant increase in the number of germ cells per tubule in both unilateral and bilateral cryptorchid boys, suggesting that buserelin treatment of the testis in a cryptorchid position is capable of improving fertility potential. If time-matched controls are compared to treated boys of the same age, again a significant difference is observed indicating that buserelin treatment does increase the germ cell count. PMID- 2891527 TI - Screening for cryptorchid boys risking sterility and results of long-term buserelin treatment after successful orchiopexy. AB - This long-term prospective follow-up study showed that in cryptorchid patients a significant correlation exists between the number of germ cells at the time of orchiopexy (prepuberty) and the spermiogram, and thus a biopsy has a prognostic value. Fifty percent of our patients had a germ cell count of less than 0.1 per tubule and belong to the risk group for sterility. Successful surgery could not induce a significant increase of germ cells in the risk group, although it does prevent secondary testicular damage. Patients with cryptorchidism developed after birth have significantly better chances of fertility than those with primary cryptorchidism. The priming effect of testosterone in the first months of life is important for male fertility. In patients belonging to the risk group treated with buserelin, a significant age-dependent increase in germ cell count occurred. PMID- 2891528 TI - Hormonal regulation of testicular descent. AB - The involvement of testosterone in testicular descent and the mechanism of testicular descent were analyzed and discussed. PMID- 2891529 TI - Development of cryptorchid testes. AB - Development of normal germ cells during childhood is a continuous process which ends at puberty. Cryptorchid gonads have severe impairment of their germ cell development which is more pronounced the higher the gonads are situated. However, all newborns with intra-abdominal testes had a normal number of germ cells. This strongly supports the theory that cryptorchidism is a disease and not a malformation. As a consequence, adequate and early treatment of cryptorchid boys should be undertaken in order to preserve good chances of fertility. PMID- 2891530 TI - Disposition of [3H]cloflumide, a new neuroleptic drug, in rats. AB - The disposition of cloflumide (VUFB 15496), 2-chloro-7-fluoro-10 [4 (carbamoylethyl)piperazino]-10,11-dihydrodibenzo [b,f] thiepin methansulfonate, a new neuroleptic agent, following single oral and intravenous dose was studied in the rat using radiotracer techniques. [3H]Cloflumide was almost completely absorbed from the gastrointestinal tract; peak plasma levels of the parent drug were attained within 4 h of oral drug administration. The mean residence time of the unchanged drug was 2.75 h after intravenous administration. The total neuroleptic activity in plasma determined by radioreceptor assay paralleled with plasma cloflumide level indicating that the dopamine inhibiting action is mediated solely by the parent drug. Concentration of radioactive substances was high in the liver and kidneys; in the brain was slightly higher than blood level. Total radioactive meterial as well as unchanged cloflumide were mostly excreted in feces (87 and 10%, respectively). At 3 days postdosing, 96% of the administered dose was recovered. PMID- 2891531 TI - Baroreceptor function in man following peripheral alpha 1- and alpha 2 adrenoceptor stimulation. AB - Methoxamine and alpha-methyl-noradrenaline were administered to six healthy male subjects on separate days as rapid bolus injections until blood pressure increased by approximately 30 mmHg; Valsalva's Manoeuvre was carried out on each occasion. Propranolol (80 mg) or placebo was administered (random order, double blind, weekly intervals) and the observations were repeated after 2 h. Baroreceptor sensitivity (delta R-R interval ms/mmHg systolic BP) was less (p less than 0.05) with alpha-methyl-noradrenaline than methoxamine. Propranolol abolished the differences in baroreceptor-mediated bradycardia following alpha methyl-noradrenaline and methoxamine, and shifted the baroreceptor sensitivity regression lines (p less than 0.05) to the left. During the release phase of Valsalva's Manoeuvre baroreceptor sensitivity was increased following propranolol. The smaller baroreceptor-mediated bradycardia response observed with alpha-methyl-noradrenaline does not support the hypothesis that pre-synaptic alpha-adrenoreceptors have a physiological role in the modulation of baroreceptor function in man, and may be due to alpha-methyl-noradrenaline having beta 1 agonist activity. PMID- 2891533 TI - Flosequinan as a third agent for the treatment of hypertension: a placebo controlled, double-blind study. AB - The acute and short term antihypertensive effect of flosequinan was determined in 16 hypertensive patients whose blood pressure was inadequately controlled despite treatment with a beta-adrenoceptor blocking agent and a diuretic. Erect and supine systolic and diastolic blood pressure was significantly reduced by flosequinan over the treatment period as compared to placebo. Heart rate was unchanged by flosequinan. Adverse effects were limited to mild headache in 3 patients and taste disturbance in 1 patient, possibly due to salivary excretion of the drug. Flosequinan is a potentially useful vasodilator for the treatment of hypertension. PMID- 2891532 TI - Absorption of an aqueous solution of a new synthetic somatostatin analogue administered to man by gavage. AB - To determine the local gastrointestinal absorption of a new synthetic somatostatin analogue (SMS 201-995 = Sandostatin), an intestinal tube was passed in eight healthy volunteers and on different days an aqueous solution was administered at four different locations: stomach, proximal duodenum, ligament of Treitz and jejunum. In a follow-up study, an oro-ileal tube was passed in six of the original volunteers and the drug solution was administered in to the terminal ileum. The aqueous solution of SMS was rapidly absorbed from the gastrointestinal tract after local application, and it was well tolerated. Absorption of the drug from the different sites was comparable, although there was a tendency to decreased peptide absorption after ileal administration. Absorption of the drug was quite variable between the subjects and the different locations. The dose corrected systemic availability relative to subcutaneous administration in another study was 0.28%. However, significant plasma SMS concentrations were achieved, suggesting that oral delivery of the polypeptide may eventually be possible for long-term treatment of a variety of disorders. PMID- 2891534 TI - Pharmacokinetics of temazepam after day-time and night-time oral administration. AB - The pharmacokinetic disposition of temazepam was compared after a day-time and night-time dose in an open randomised crossover study. Twelve healthy male volunteers received a single oral dose of 20 mg temazepam in a soft gelatine capsule at 0900 h or 2200 h. Blood samples were taken immediately before dosing and at selected times over the 36-h period after each dose. The absorption of temazepam was slower after evening administration; the absorption half-life and time to reach maximal plasma concentration being 0.53 h and 1.67 h respectively, compared to 0.38 h and 1.02 h following morning administration. Considering distribution characteristics, evening administration produced a lower peak plasma temazepam concentration (362 ng/ml) compared with a day-time level of 510 ng/ml. Distribution half-life after night-time administration was increased compared with day-time administration (1.76 h vs 1.03 h). A significantly higher percentage of the drug, relative to Cmax, remained in the plasma at 8 and 24 h after evening dosing (39.3 and 15.4% compared to 24.7 and 11.2% following day time administration). In spite of the half-lives of absorption, distribution and elimination all being longer after the evening dose, the overall bioavailability, as measured by the area under the curve (AUC) was comparable after the two times of administration. Similarly the difference in the mean residence time (MRT) of the two doses was within accepted limits. It is concluded that a chronopharmacokinetic effect was seen for temazepam; however it is unlikely to be of any clinical significance. PMID- 2891535 TI - Pharmacokinetics and pharmacodynamics of thiazinamium in asthmatic patients. AB - The pharmacokinetics and pharmacodynamics of thiazinamium (Multergan) were studied after intravenous and intramuscular administration to 7 males with chronic reversible airways obstruction. Disposition after i.v. administration was described by a clearance of 0.54 l.min-1, central compartment volume of 14.8 l, distribution rate constant 0.092 min-1, and an elimination rate constant of 0.0044 min-1. The corresponding estimates after i.m. administration were 0.324 l.min-1, 34.1 l, 0.035 min-1, and 0.0018 min-1. The bronchodilator response (expressed as % predicted FEV1) after i.v. administration was characterized by maximum increase in FEV1 of 33.9%, with an EC50 of 12.8 ng.ml-1 and an equilibration half-time of 11 min. Corresponding parameter estimates after i.m. administration were 32.2%, 18.8 ng.ml-1, and 9 min. Anticholinergic activity, measured by the change in heart rate after i.v. administration, showed maximum increase of 76 beats.min-1, with an EC50 of 176 ng.ml-1 and an equilibration half time of 1.3 min. After i.m. administration the corresponding values were 120 beats.min-1, 250 ng.ml-1, and 3 min. The optimal plasma concentration of thiazinamium was about 100 ng.ml-1, which should give a near maximal bronchodilator response (over 80% of predicted normal) and a heart rate of about 100 beats.min-1. PMID- 2891536 TI - Effect of 6-hourly intermittent intravenous boluses of oxmetidine and ranitidine on gastric acidity and serum prolactin. AB - The effect on 24-h gastric juice volume and pH of 30 min intravenous infusions of 200 and 400 mg oxmetidine and 50 mg ranitidine, administered at 6-hourly intervals, has been investigated in 12 healthy male subjects. After each infusion period a median intragastric pH greater than 5 was obtained with all active treatments, which also caused a significantly elevated 24-h median pH versus placebo. The 24-h median pH following ranitidine did not differ significantly from that after either oxmetidine treatment. There was a sharp decrease in gastric volume secretion within 2 h of infusion of each active treatment. There was no significant difference between active treatments in the time required to reach an intragastric pH greater than 5. No active treatment was able to maintain the pH greater than 5 for longer than 4 h (average 3 h). It is concluded that in patients at risk of stress ulcer, continuous infusion therapy with H2-blockers should be employed both for pharmacokinetic and practical reasons. It should be accompanied by regular measurement of pH in order to monitor any fall in pH. Alternatively, shorter time intervals than 6 h should be used for bolus therapy. PMID- 2891538 TI - Differentiation of B cell progenitors in vitro: generation of surface IgM+ B cells, including Ly-1 B cells, from Thy-1- asialoGM1+ cells in newborn liver. AB - We have established a stromal adherent cell line (ST2) from fetal liver that promotes growth and differentiation of early B lineage cells. Many cells in the "null population" (3-5%) from newborn liver that lack antigens found on mature erythroid, myeloid or lymphoid cells proliferate extensively on this ST2 layer. Further division of this cell fraction on the basis of Thy-1 and asialoGM1 (aGM1) expression discriminates cells that predominantly proliferate from those that differentiate on the ST2 layer. Among four populations, Thy-1+ aGM1- cells proliferate most but yield few B220+ cells. In contrast, Thy-1- aGM1+ cells proliferate to a very limited extent, but most (greater than 90%) start to express B220 and a large fraction (up to 50%) become surface IgM+ after 2 weeks of culture. These B cells include cells expressing the pan-T cell molecule Ly-1, that is, Ly-1 B cells. Curiously, this Thy-1- aGM1+ cell population is largely absent from bone marrow in adult mice. PMID- 2891537 TI - Adrenergic system and carbohydrate metabolism. Effects of beta-receptor blockade on insulin secretion and peripheral insulin sensitivity in normoglycaemic patients. AB - The effects of 3 weeks of treatment with the beta-receptor blocking agent propranolol and a placebo on glucose tolerance, insulin secretion and peripheral insulin sensitivity have been evaluated in 7 normoglycaemic hypertensive patients by an oral glucose tolerance test and the insulin clamp technique. Significant changes in systolic and diastolic blood pressure and heart rate were observed at the end of propranolol treatment, but there were no associated changes in glucose tolerance, insulin secretion or peripheral insulin sensitivity. No difference was observed in glucagon, growth hormone and free fatty acids between propranolol and placebo treatment. The results support the view that the hypothetical pancreatic glucoreceptor, at least in non-acute studies, is not affected by beta blockade. In addition, there was no effect on tissue sensitivity to insulin. PMID- 2891539 TI - The role of dipeptidyl peptidase IV in human T lymphocyte activation. Inhibitors and antibodies against dipeptidyl peptidase IV suppress lymphocyte proliferation and immunoglobulin synthesis in vitro. AB - Dipeptidyl peptidase IV (DP IV), an ectoenzyme in the cell membrane of T lymphocytes, is an important constituent in the process of lymphocyte activation. This conclusion is drawn from the following observations: (a) Proliferation of peripheral blood lymphocytes induced by mitogenic lectins (phytohemagglutinin, concanavalin A, pokeweed mitogen) is suppressed in the presence of DP IV inhibitors. This effect is specific and applies to an irreversible suicide inhibitor as well as to a competitive one in a dose-dependent fashion. (b) Inhibition of DNA synthesis was also induced by a polyclonal anti-DP IV immunoglobulin. (c) As a consequence of impaired T cell function the production of immunoglobulins by pokeweed mitogen-stimulated lymphocytes is also markedly reduced in the presence of DP IV inhibitors. PMID- 2891541 TI - Beta-adrenoceptor stimulation and blockade during myocardial ischemia in dogs: effect on cardiac O2 supply and consumption. AB - The effect of beta-adrenoceptor blockade and activation on ischemic regional and microregional myocardial O2 supply/consumption parameters was assessed in 28 open chest, anesthetized dogs. Ten minutes after LAD occlusion, dogs were given i.v. saline, 2 mg/kg propranolol, 0.2 mg/kg pindolol, or 1 microgram/kg per min isoproterenol. Coronary blood flow was determined using radioactive microspheres before and 2 h after LAD occlusion while O2 supply/consumption parameters were determined using microspectrophotometry. Ischemia resulted in a 66% reduction in subendocardial flow in controls in the ischemic zone and no experimental treatment significantly altered this flow. Pindolol resulted in a significant improvement in the ischemic regional subendocardial/subepicardial flow ratio (from 0.69 in the control ischemic region to 0.88 during pindolol treatment). O2 extractions were significantly increased and O2 consumptions were significantly depressed in the ischemic regions of all groups. O2 extractions were increased to a lesser degree in the ischemic region with the use of pindolol and propranolol. Propranolol and pindolol both significantly decreased the proportion of veins with low (0-20%) O2 saturations in the ischemic region indicating an improved microregional distribution of blood flow and/or O2 consumption within the ischemic region. PMID- 2891540 TI - Purified lymphocyte function-associated antigen-3 and T11 target structure are active in CD2-mediated T cell stimulation. AB - In this study we have used cells expressing LFA-3 or T11TS, the human and sheep forms of the ligand of CD2, as well as the purified LFA-3 and T11TS molecules themselves to study their effects on T cell activation via the CD2-mediated "alternative pathway". Sheep red blood cells, which bind to CD2 via T11TS in E rosette formation, and human autologous monocytes, which express the LFA-3 molecule, both induce proliferation of resting T cells in the presence of per se submitogenic concentrations of anti-T11(2) plus anti-T11(3) monoclonal antibodies (mAb). This effect is blocked by mAb to LFA-3, T11TS and CD2 known to inhibit CD2 ligand interaction. In addition, purified LFA-3 and T11TS, when added at ng amounts to cultures containing submitogenic concentrations of anti-T11(2 + 3) mAb, are also strongly mitogenic for resting human T cells. Thus, both LFA-3 and T11TS are potent co-stimulators of the alternative pathway of T cell activation but by themselves do not provide a mitogenic signal. This finding is discussed with regard to a physiological role of CD2-LFA-3 interaction in T cell activation. PMID- 2891542 TI - Pituitary-adrenal mediation of dermorphin-induced inhibition of gastric emptying in rats. AB - The role of the pituitary-adrenal axis in the inhibition of gastric emptying caused by intracerebroventricular (i.c.v.) administration of dermorphin was examined. Dermorphin given i.c.v. (1, 10, 100 ng per rat) slowed emptying in a dose-related manner. Hypophysectomy or sub-diaphragmatic bivagotomy reduced, and adrenalectomy prevented the inhibition of gastric emptying associated with dermorphin. Dermorphin inhibition of gastric emptying is thus specially dependent upon intact adrenals. PMID- 2891543 TI - The effect of agonists at the GABA-benzodiazepine receptor complex on the duration of immobility of mice in the forced swimming test. AB - In the present study, we examined the effect of various agents which affect in a different manner the GABA-benzodiazepine receptor-chloride ionophore complex system in relation to the immobile behavior of mice in the forced swimming test. The benzodiazepines diazepam and flurazepam, the barbiturates pentobarbital and phenobarbital, zopiclone and beta-CCP (propyl-beta-carboline-3-carboxylate) enhanced the immobile behavior in a dose-dependent manner. In the doses used here, these agents produced almost no muscle relaxant action. Ro15-1788 and beta CCM (methyl-beta-carboline-3-carboxylate) themselves had no effect on the duration of immobility. However, Ro15-1788 and beta-CCM reversed the enhancing effect produced by all 6 drugs. These results indicate that the enhancement of the duration of immobility of mice may be somehow correlated to the anxiolytic action but not to the muscle relaxant action. The effect may be mainly mediated by the benzodiazepine receptor, which forms a part of the GABA-benzodiazepine receptor-chloride ionophore complex. Furthermore it is suggested that there were behavioral similarities in the effects of beta-CCP and benzodiazepines. PMID- 2891544 TI - The D-1 antagonist SCH 23390 stimulates while the D-1 agonist SKF 38393 fails to affect dopamine release in the dorsal caudate of freely moving rats. AB - SCH 23390, from doses of 0.012 mg/kg s.c., dose dependently stimulated the release of dopamine (DA) and the output of its metabolites, dihydroxyphenylacetic acid and homovanillic acid, in the dorsal caudate of freely moving rats implanted with transcerebral dialysis fibers. SKF 38393 failed to modify DA release and metabolism at doses of 5, 10 and 25 mg/kg s.c. but at 25 mg/kg s.c. it abolished the effect of 0.025 mg/kg of SCH 23390. Administration of gamma-butyrolactone (700 mg/kg s.c.), which blocks the firing of DA neurons, prevented the effect of 0.050 mg/kg s.c. SCH 23390. The results indicate that D-1 receptors control the release of DA, probably through stimulation of the firing of DA neurons. PMID- 2891545 TI - Synaptosomal free [Ca2+] is reduced by clonidine and dynorphin A-(1-13) and increased by idazoxan. AB - Intrasynaptosomal free calcium concentrations measured in rat cortical synaptosomes using the calcium sensitive fluorescent dye quin 2, were found to be 0.107-0.122 microM (n = 33). Stimulation of alpha 2-adrenoceptors or kappa-opiate receptors with clonidine (0.1-100 microM) or dynorphin A fragment (1-13) (0.2-5.0 microM) respectively, produced a dose dependent reduction in the intrasynaptosomal free calcium concentration. The alpha 2-adrenoceptor mediated reduction produced by clonidine (100 microM) was antagonised by the selective alpha 2-antagonist idazoxan (RX781094) (200 microM). Dynorphin A-(1-13) (1 microM) caused a reduction which was antagonised by a high (20 microM) but not low (2.0 microM) concentration of naloxone. We conclude that unlike the mu- and delta-opiate receptor, stimulation of alpha 2-adrenoceptors or kappa-opiate receptors elicits changes in intrasynaptosomal free calcium concentration which are independent of the voltage sensitive calcium channel. This does not preclude the possibility that the alpha 2-adrenoceptor and kappa-opiate receptor also have an effect at the voltage sensitive calcium channel. PMID- 2891546 TI - Bradykinin receptor antagonists used to characterize the heterogeneity of bradykinin-induced responses in rat vas deferens. AB - The application of bradykinin to the isolated, transmurally stimulated rat vas deferens caused two effects: increase of the basal tension of the tissue and potentiation of the magnitude of electrically driven twitches. These bradykinin responses were not evenly distributed along the ductus. The direct contractile action of bradykinin was found to be stronger in the epididymal half of the tissue while the potentiation of the muscle twitches was more pronounced in the prostatic half of the rat ductus. Bradykinin is more potent to potentiate the electrically driven twitches than to act as a postjunctional agonist. Tyr bradykinin, [Tyr5]bradykinin and [Tyr8]bradykinin exhibited significant differences in the potency ratio to produce each of these responses. [Thi5,8,D Phe7]bradykinin is a weak postjunctional agonist but was a full agonist to potentiate the electrically induced twitches. Furthermore, this compound antagonized the bradykinin-induced contractions. [Hyp3,Thi5,8,D-Phe7]bradykinin was devoid of agonist activity at either pre- or postjunctional sites; it behaved as a pure antagonist and was more than potent its non-hydroxylated analog. The addition of a D-Arg residue at the amino terminal increased the antagonist potency significantly. The pA2 of D-Arg-[Hyp3,Thi5,8,D-Phe7]bradykinin to antagonize the postjunctional effect of bradykinin was 6.35, a value that differed significantly from the value of 6.93 required to block the prejunctional effect of the peptide. The bradykinin receptor antagonists did not modify significantly the magnitude of the contractile responses caused by angiotensin II, norepinephrine or 5-hydroxy-tryptamine. PMID- 2891547 TI - Alpha 1- and alpha 2-adrenoceptor activation increases plasma glucagon levels in the mouse. AB - The effects of activation of the alpha-adrenoceptors on glucagon secretion are not yet clear. We therefore injected the alpha 1-selective agonist phenylephrine and the alpha 2-selective agonist clonidine (0.05-50 nmol/kg) intravenously to mice and measured the plasma glucagon levels. We found that both phenylephrine and clonidine enhanced the plasma glucagon levels. The peak level of plasma glucagon was seen at 2 min after clonidine injection whereas phenylephrine enhanced the plasma glucagon levels throughout a 10 min period after the injection. Furthermore, both clonidine and phenylephrine potentiated the plasma glucagon response to the cholinergic agonist carbachol and exerted additive stimulatory effects on the plasma glucagon response to both the beta-adrenoceptor agonist terbutaline and the C-terminal octapeptide of cholecystokinin, CCK-8. The elevated plasma insulin levels after injection of carbachol or terbutaline were lowered by clonidine but not by phenylephrine whereas the CCK-8-induced increase in plasma insulin levels was not affected by either clonidine or phenylephrine. We conclude that both alpha 1- and alpha 2-adrenoceptor activation enhances plasma glucagon levels in the mouse, and that alpha 2- but not alpha 1 adrenoceptor activation lowers plasma insulin levels. PMID- 2891548 TI - Electrophysiological evidence for an alpha 2-adrenergic inhibitory control of transmitter release in the rabbit mesenteric artery. AB - Excitatory junction potentials (e.j.p.s) evoked by nerve stimulation with 15 pulses at 1 Hz were recorded from muscle cells of the rabbit isolated mesenteric artery. Clonidine and B-HT 933 depressed all e.j.p.s in the train. The percentage inhibition was inversely related to the number of pulses. Yohimbine, rauwolscine and tolazoline reduced the early e.j.p. amplitudes but enhanced the later ones. The percentage facilitation of e.j.p.s increased with the number of pulses until a maximum was reached. Prazosin and corynanthine did not influence the first few e.j.p.s but potentiated the subsequent ones; their effects were less pronounced than those of yohimbine and rauwolscine. All the drugs antagonized the inhibition by clonidine but the effects of yohimbine and rauwolscine were more marked than those of prazosin and corynanthine. Phenylephrine, St 587 and noradrenaline depressed the e.j.p.s. Yohimbine diminished the effects of these substances and was a stronger antagonist of phenylephrine than prazosin. We suggest that, in the rabbit mesenteric artery, noradrenaline and the neuroeffector transmitter (probably ATP) are co-released from the terminals of postganglionic sympathetic nerves. Noradrenaline activates presynaptic alpha 2-adrenoceptors and thereby depresses transmitter release. The degree of presynaptic inhibition depends on the number of pulses applied, i.e. on the biophase concentration of noradrenaline. PMID- 2891549 TI - Lidamidine inhibits intrinsic contractile patterns of the rat proximal colon. AB - Lidamidine is a clinically effective antidiarrheal agent that inhibits intestinal secretion, reduces intestinal transit, and inhibits smooth muscle contraction. Yet, its specific effects upon colonic motility have not been thoroughly examined. The purpose of our studies was to examine lidamidine's inhibitory effects upon colonic contractile patterns in the rat and identify the responsible receptor mechanism. Fasted male rats were anesthetised and equipped with an intraluminal cannula positioned at the proximal end of a 10 cm fluid-filled segment of the ascending colon (basal pressure, 10 cm H2O). Intraluminal pressure was monitored by a transducer attached to a closed fluid-filled system. All drugs were administered intravenously by slow infusion. A regular pattern of distinct contractile complexes was observed over a 70 min period. These contractions increased intraluminal pressure to 39 +/- 1.2 cm H2O (mean +/- S.E.), occurred at a frequency of 0.3 per min and lasted from 1 to 2.5 min. Inhibition of these contractile patterns was observed with either atropine (0.1 mg/kg) or lidamidine (3.0 mg/kg). A 20 min pretreatment with idazoxan (3.0 mg/kg) antagonized lidamidine's but not atropine's effect. Trimazosin (1 mg/kg) or propranolol (0.3 mg/kg) pretreatment did not antagonize the lidamidine-generated inhibition. These results indicate that lidamidine inhibits an intrinsically generated, cholinergically controlled pattern of colonic contractions primarily by an alpha 2-receptor-mediated mechanism. PMID- 2891550 TI - Antagonism by neuroleptics of serotonin 5-HT1A and 5-HT2 receptors of normal human brain in vitro. AB - Using radioligand binding techniques and human frontal cortex, we determined the equilibrium dissociation constants (KDs) of 17 neuroleptics at the serotonin 5 HT1A and serotonin 5-HT2 receptors with [3H]WB4101 and [3H]ketanserin, respectively. At the serotonin 5-HT1A receptor, the most and least potent neuroleptics were chlorprothixene (KD = 230 nM) and fluphenazine (KD = 40 microM), respectively. At the serotonin 5-HT2 receptor, the most and least potent neuroleptics were spiperone (KD = 0.38 nM) and molindone, (KD = 5 microM), respectively. PMID- 2891551 TI - The effect of neuropeptide Y (NPY) on stimulation-evoked release of [3H]norepinephrine (NE) from rat hypothalamic and cerebral cortical slices. AB - The effects of neuropeptide Y (NPY) on stimulation-evoked release of [3H]norepinephrine ([3H]NE) in rat hypothalamic and cerebral cortical slices were investigated. NPY inhibits the stimulation-evoked release of [3H]NE from hypothalamic, but not from cerebral cortical slices. NPY potentiates the inhibition of [3H]NE release by the alpha 2-agonist UK 14,304 in the hypothalamic slices. The blockade of alpha 2-adrenoceptors by RX 781094 diminishes the inhibitory effects of NPY. These results suggest that in the hypothalamic slices the action of NPY might be in part mediated by the alpha 2-adrenoceptors. PMID- 2891552 TI - Inhibitory effects of noradrenaline and dopamine on calcium influx and neurotransmitter glutamate release in mammalian brain slices. AB - Noradrenaline and dopamine (0.1-100 microM) inhibited 45Ca2+ uptake and glutamate release induced by veratrine (25 microM) in cortical and striatal slices but were without effect when added alone. Each parameter was inhibited in a dose-dependent manner by noradrenaline in cortical slices (IC50 = 0.05 microM) and by dopamine in striatal slices (IC50 = 0.08 microM). Noradrenaline (0.01-100 microM) was without influence on veratrine-induced 45Ca2+ influx or glutamate release in the striatal preparation, and likewise dopamine was inactive in cortex slices. The use of adrenoceptor antagonists suggests that the action of noradrenaline is mediated by the alpha 2-receptor which is thought to be adenylate cyclase linked. Dopamine appeared to be acting through the D-2 receptor. PMID- 2891553 TI - Pharmacological analysis of 5-HT-induced vasoconstriction in isolated, perfused dog skeletal muscle arteries. AB - The mechanism of the vasoconstriction caused by 5-HT was analysed pharmacologically in isolated, perfused skeletal muscle branches of the canine femoral artery. An intraluminal injection of serotonin (5-HT) produced a marked vasoconstriction and the dose-response curve was bell-shaped. The 5-HT-induced response was inhibited by methysergide and ketanserin but a larger dose of ketanserin (10-30 micrograms) reduced the maximal responses to 5-HT, indicating its general depressant action. Norepinephrine (NE) and KCl-induced constrictions were not significantly affected by methysergide. Ketanserin significantly suppressed the NE-induced response at a relatively large dose but not the KCl induced one. 5-HT- and KCl-induced constrictions were not modified by a potent alpha 1-adrenoceptor antagonist, bunazosin. It is considered that 5-HT may mediate its contractile effect on these arteries via specific 5-HT2 receptors but not alpha-adrenoceptors. Diltiazem at a relatively large dose (30-100 micrograms) slightly but significantly depressed NE-induced constrictions, and KCl-induced responses were markedly depressed by diltiazem (10-100 micrograms). On the other hand, 5-HT-induced constrictions were not suppressed by diltiazem at any of the doses used. It was shown that cold storage (at 4 degrees C, for 3-7 days) did not significantly modify 5-HT-induced responses although the KCl-induced effects were suppressed. Thus, it is considered that the calcium channel in these vessels may be dominantly depressed by cold storage. It is concluded that 5-HT-induced constriction in skeletal muscle arteries may be independent of the influx of extracellular Ca ions. PMID- 2891554 TI - Behavioral effects of several new anxiolytics and putative anxiolytics. AB - The behavioral effects of several new anxiolytics and putative anxiolytics were evaluated in two tests sensitive for anxiolytic activity. In the first test, rats were trained to lever-respond for sweetened milk under a multiple variable interval fixed-ratio (VI-FR) schedule of reinforcement. In the FR component a brief electric shock coincided with the presentation of reward (i.e. conflict procedure). Treatment of these rats with diazepam, tracazolate, CGS-9896, and the pyrimidinylpiperazine derivatives buspirone, gepirone and ipsapirone (TVX Q 7821) significantly increased responding that was suppressed by foot-shock. A common metabolite of the pyrimidinylpiperazines, l-PP, had no affect on punished responding. A second group of rats was trained to discriminate diazepam from saline using a two-lever operant choice procedure. Diazepam-stimulus generalization occurred to CGS-9896, CL 218,872, zopiclone and tracazolate, but not to buspirone, gepirone, ipsapirone or l-PP. It was concluded that while all of the new compounds examined appear to share an anxiolytic effect as demonstrated by their activity in the conflict procedure, the pyrimidinylpiperazine agents do not share discriminative stimulus properties which are common to drugs which act via the benzodiazepine receptor. PMID- 2891555 TI - Different dopamine receptor subtypes mediate the neurogenic vasodilation produced by fenoldopam and SK & F 85174 in the dog hindlimb. AB - The present study was performed to examine the effects of the mixed DA-1/DA-2 receptor agonist. SK & F 85174, on hindlimb vascular resistance and identify the DA receptor subtypes involved in the neurogenic hindlimb vasodilation produced by this compound. Bilateral hindlimb perfusion at controlled flow rates was carried out in anesthetized dogs and one hindlimb was surgically denervated whereas the other limb was kept neurally intact. Intravenous administration of SK & F 85174 and fenoldopam, a DA-1 receptor agonist, produced decreases in mean blood pressure and in the perfusion pressure in the innervated limb. Perfusion pressure in the denervated limb was not altered by fenoldopam and was increased by SK & F 85174. The DA-2 receptor antagonist, S-sulpiride, inhibited the neurogenic vasodilation produced by SK & F 85174 but not that produced by fenoldopam. The DA 1 receptor antagonist, SCH 23390, did not alter the hindlimb vasodilatory effects of either SK & F 85174 or fenoldopam in these animals, but it antagonized the hypotensive responses to both of these agents. Intra-aortic administration of SK & F 85174 and fenoldopam also resulted in neurogenic hindlimb vasodilation with the maximum response to fenoldopam occurring significantly faster than SK & F 85174 (2.5 +/- 0.16 vs. 9.8 +/- 1.2 s). S-Sulpiride antagonized the hindlimb vasodilation produced by SK & F 85174 but not by fenoldopam. R-Sulpiride antagonized the hindlimb vasodilatory effect of fenoldopam.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891556 TI - Isolation of hemopoietic stem cell subsets from murine bone marrow: I. Radioprotective ability of purified cell suspensions differing in the proportion of day-7 and day-12 CFU-S. AB - We have studied the ability of bone marrow cell suspensions greatly differing in the relative proportion of day-7 and day-12 spleen colony-forming units (CFU-S) to rescue mice from radiation-inflicted death, and to repopulate the irradiated bone marrow and spleen with nucleated cells. Counterflow centrifugal elutriation in combination with removal of adherent cells and fluorescence-activated cell sorting on differences in wheat germ agglutinin (WGA)-fluorescein isothiocyanate (FITC) affinity and light scatter properties were used consecutively to enrich large numbers of hemopoietic stem cells from mouse bone marrow. Enrichments of 50 to 200-fold have been achieved for day-12 CFU-S and radioprotective ability (RPA), permitting 50% of lethally irradiated mice to survive over a period of 30 days with as few as 50-80 donor cells. The ratio of day-7 and day-12 CFU-S in the various suspensions could be significantly modulated on the basis of their WGA binding and perpendicular light scatter characteristics. This finding enabled us to investigate the properties of day-7 and day-12 CFU-S with respect to their RPA. We found a highly significant log/log relationship between enrichment factors for (1) RPA, (2) the number of day-12 CFU-S, and (3) spleen cellularity as measured on day 13. In addition, similar numbers of sorted and unfractionated day-12 CFU-S were required to obtain the same level of protection. Enrichment for RPA was significantly less related to either the number of day-7 CFU-S injected, or the bone marrow cellularity of the irradiated mice on day 13. PMID- 2891557 TI - Isolation of hemopoietic stem cell subsets from murine bone marrow: II. Evidence for an early precursor of day-12 CFU-S and cells associated with radioprotective ability. AB - Counterflow centrifugal elutriation (CCE) in combination with plastic adherence and fluorescence-activated cell sorting were used consecutively to enrich functionally different subpopulations of pluripotent hemopoietic stem cells (HSC) from mouse bone marrow. The nonadherent CCE fractions were labeled with wheat germ agglutinin (WGA)-fluorescein isothiocyanate (FITC) and sorted according to differences in fluorescence within various windows on the basis of forward (FLS) and perpendicular (PLS) light scatter. The sorted cells were then assayed for their (1) in vivo colony-forming ability (day-7 and day-12 spleen colony-forming units [CFU-S]), (2) radioprotective ability (RPA; 30-day survival), and (3) their ability to repopulate the bone marrow or spleen over a 13-day period with day-12 CFU-S, granulocyte-macrophage colony-forming units (CFU-GM), nucleated cells, or cells associated with RPA. The highest incidence of day-12 CFU-S and cells with RPA was obtained by sorting the most WGA-positive cells with relatively high PLS (enrichment, 50- to 200-fold), lowering the effective dose (ED 50/30) to an average of 80 cells. The separative procedure enabled hemopoietic stem cells that repopulate both bone marrow and spleen with secondary RPA cells, CFU-S-12, and CFU-GM to be enriched and separated from part of the RPA cells, CFU-S-12, and cells that reconstitute the cellularity of bone marrow and spleen. These data suggest that cells generating both day-12 CFU-S and RPA cells differ from day-12 CFU-S and RPA cells themselves on the basis of PLS characteristics and affinity for WGA. Such early stem cells have also been detected in sorted fractions meeting the FLS/PLS characteristics of lymphocytes. PMID- 2891558 TI - The decrease in long-term marrow repopulating capacity seen after transplantation is not the result of irradiation-induced stromal injury. AB - Marrow cells from nonirradiated F1-W/Wv mice repopulated slightly less well than cells from lethally irradiated recipients. Therefore, avoiding irradiation of recipients did not improve the relative repopulating ability of their marrow cells. In other experiments, F1-W/Wv mice were transplanted by parabiosis with marrow of WBB6F1-+/+ (F1-+/+) mice, avoiding cellular handling and irradiation. Marrow cells transplanted to F1-W/Wv mice by this procedure demonstrated slightly better repopulating ability than did marrow cells transplanted by injection. However, they performed no better than those transplanted by parabiosis to irradiated F1-+/+ recipients. Significant impairment of stromal function after irradiation was not indicated. Apparently, stem cell damage caused by transplantation may have greater importance in causing loss of stem cell replicative potential than effects of irradiation-induced stromal injury. PMID- 2891559 TI - Tyrosine hydroxylase-immunoreactive intrinsic neurons in the rat cerebral cortex. AB - Using specific antisera against the catecholamine synthesizing enzyme, tyrosine hydroxylase (TH), in combination with the peroxidase-antiperoxidase method and/or the avidin-biotin complex method, we have found a new group of TH immunoreactive (TH-I) neurons in the rat cerebral cortex. Numerous TH-I cells were observed all over the isocortex, that is, frontal, temporal, parietal and occipital regions, and in some parts of the allocortex such as the anterior cingulate cortex, the retrosplenial cortex and anterior part of the insular cortex. In contrast, they were rare in the perirhinal cortex, posterior part of the insular cortex, piriform cortex, entorhinal cortex and hippocampal formation. TH-I cells were situated throughout all cortical layers, but were most concentrated in layer II/III. Although TH-I cells were heterogeneous in shape, the majority were bipolar. All TH-I cells so far examined appeared to be of the nonpyramidal type. The majority of these intrinsic TH-I neurons also contained the GABA-like immunoreactivity and thus could be regarded as a subpopulation of cortical GABAergic neurons. PMID- 2891560 TI - Dopamine and somatostatin modulated adenylate cyclase activity in the rat caudate putamen following unilateral cortical ablation. AB - Dopamine and somatostatin-14 (SRIF) were incubated with a membrane fraction of rat caudate-putamen (CP) tissue in an adenylate cyclase assay in order to examine the D-1-receptor coupled adenylate cyclase activity 5 days and 3 weeks after unilateral ablation of the left frontal and lateral cortex. Five days after decortication the ipsilateral basal and dopamine stimulated adenylate cyclase activity was increased by about 30% compared to that of the contralateral side. Three weeks after decortication no significant difference could be seen. On either side basal and dopamine stimulated adenylate cyclase activity was not significantly decreased compared to sham operated controls. Somatostatin (10(-7) mol/l) reduced basal adenylate cyclase activity of the ipsilateral CP five days following lesioning and reduced the maximal stimulation induced by dopamine. The effects of somatostatin were most marked in the absence and at low concentrations of dopamine (10(-7)-10(-6) mol/l). The effects of somatostatin in the lesioned CP were no longer apparent three weeks following surgery. These results do not favour a presynaptic localization of D-1-receptors on cortico-striate projection fibers and suggest that somatostatin is involved in the interaction of the cortico-striate and nigro-striatal projection systems and may play a role in the regulation of D-1-receptor linked adenylate cyclase. PMID- 2891561 TI - Anomeric specificity of glucose-induced somatostatin secretion. AB - In isolated perfused rat pancreases, the alpha-anomer of D-glucose is more potent than beta-D-glucose not solely in stimulating insulin release and suppressing glucagon output, but also in causing somatostatin secretion. PMID- 2891562 TI - Analysis of pharmaceutical solid forms by diffuse infrared reflectance spectroscopy. Note II. PMID- 2891563 TI - [Influence of klofelin on the analgesic and autonomotropic effects of narcotic analgesics]. AB - In conscious rats clopheline (0.1-0.25 mg/kg), in contrast to promedol, morphine and fentanyl administered at analgesic doses, suppressed nociceptive reactions of arterial blood pressure produced by a mechanical stimulation and intracardiac infusion of bradykinin. The use of clopheline in combination with narcotic analgesics potentiated the analgesic effect and significantly inhibited nociceptive hemodynamic reactions without changing the background level of arterial blood pressure. PMID- 2891564 TI - [Systems analysis of the effect of fenazepam on animal behavior by the methods of the pattern recognition theory]. AB - The pattern recognition theory was used to demonstrate that phenazepam effect on the differentiation of structured visual stimuli by animals is connected with the alteration of the processes of visual information elaboration in the somatosensory and association cortex. PMID- 2891565 TI - [Effect of nonselective and cardioselective beta-adrenergic blockade on fatty acid metabolism in the myocardium]. AB - Effects of beta-adrenoblocker obsidan and selective beta-adrenoblocker cordanum on metabolism of fatty acids in the rat myocardium were studied. Obsidan increased the concentration of triglycerides and decreased that of nonesterified fatty acids in the myocardial tissue, reduced the amounts of ketone bodies, beta oxybutyrate and acetoacetate, accelerated oxidation of fatty acids by myocardial mitochondria. Cordanum produced no changes in beta-oxybutyrate concentration, decreased the concentrations of acetoacetate, induced accumulation of triglycerides. The drug reduced respiration control at the expense of an increase in controlled respiration rate. Thus, in contrast to total beta-adrenergic blockade induced by obsidan, cardioselective beta-adrenergic blockade by cordanum results in a decrease of myocardial oxygen consumption and a reduction of respiration controlled respiration rate. PMID- 2891566 TI - [Effect of ildamen on the heart conduction system in ischemic heart disease patients]. AB - Thirty-four patients with ischemic heart disease (IHD) were studied: 18 IHD patients with latent forms of disturbances of conductivity in the atrioventricular junction and sinus node sickness syndrome revealed at frequency stimulation of the heart; 16 patients with acute myocardial infarction complicated with the atrioventricular junction blockade of II and III degrees. Ildamen solution (4 mg) was slowly intravenously infused to all patients under study. Exerting the beta-stimulating effect, ildamen positively influences restoration of the disordered function of the pacemaker and conduction system of the heart: through immediate action on these systems and an increase of the coronary blood flow contributing to improvement of nutrition of the condition system of the heart. PMID- 2891567 TI - Clostridium perfringens iota toxin ADP-ribosylates skeletal muscle actin in Arg 177. AB - Clostridium perfringens iota toxin ADP-ribosylates actin. Substrates of C. perfringens toxin are both non-muscle beta/gamma-actin and skeletal muscle actin. This finding suggests that C. perfringens iota ADP-ribosylates the same amino acid in skeletal muscle and non-muscle actin as does C. botulinum C2 toxin in non muscle actin. Protein chemical analysis involving thermolysin cleavage on [32P]ADP-ribosylated actin or tryptic digestion followed by a secondary thermolysin cleavage of the radiolabelled fragments showed one major site of ADP ribosylation. From its amino acid composition and sequence, the radiolabelled peptide was identified as peptide 175-177, locating the acceptor ADP-ribosyl amino acid as Arg-177. PMID- 2891568 TI - Familial cancer: opportunities for clinical practice and research. AB - Families carrying an inherited risk of cancer are important for two reasons. In clinical practice they may provide opportunities for early diagnosis or prevention. They are of interest for research because the inherited gene may increase the risk of a specific cancer by 1000-fold or more, and we would like to know what these genes do. PMID- 2891569 TI - [Characteristics of the feldsher's work with middle-aged and elderly persons]. PMID- 2891570 TI - [Role of the family in the prevention of alcoholism (material for talks)]. PMID- 2891571 TI - [Joint work of the feldsher with the biology teacher in the hygiene education of schoolchildren]. PMID- 2891572 TI - [The history of paramedical education]. PMID- 2891574 TI - [Late orthodontic management and prosthetic rehabilitation of a child after accidental injuries]. PMID- 2891573 TI - [Hemorrhagic fever with renal syndrome]. PMID- 2891575 TI - Enhanced proteolytic susceptibility of oxidized proteins. PMID- 2891576 TI - Central versus peripheral effect of clonidine on hepatic venous plasma glucose concentrations in fasted rats. AB - To evaluate whether clonidine exerts its action within the central nervous system or outside the central nervous system to induce hyperglycemia, we compared the effects of clonidine injected into the third cerebral ventricle or intravenously on hepatic venous plasma glucose concentrations in fasted rats. Clonidine administration produced a dose-dependent hyperglycemia in each case. At all tested doses (5, 50, and 100 nmol) the hyperglycemic responses to clonidine injected intravenously were not significantly different from those to clonidine injected into the third cerebral ventricle. Intraperitoneal pretreatment with yohimbine (50 nmol) or phentolamine (50 nmol), both alpha-adrenergic antagonists, reduced the hyperglycemic response to clonidine (100 nmol) given intravenously, but these antagonists preinjected into the third cerebral ventricle did not reduce the response. Moreover, no significant differences in venous plasma clonidine concentrations were observed when intravenous and third cerebral ventricle injections of clonidine (100 nmol) were compared. These results suggest that clonidine-induced hyperglycemia is mainly mediated by the peripheral mechanism rather than through the central mechanism. To gain an insight into the peripheral mechanism for the hyperglycemic action of clonidine, we measured the plasma immunoreactive glucagon and insulin concentrations after intravenous clonidine (100 nmol). We found that plasma immunoreactive glucagon concentrations significantly increased, whereas plasma immunoreactive insulin concentrations did not change significantly despite hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891577 TI - [Artificial stable functional feedback and the neuroregulatory correction of psychoautonomic disorders]. PMID- 2891578 TI - Neurotransmitters: past, present, and future directions. AB - As originally conceived, central neurotransmitters operated uniformly, exciting or inhibiting postsynaptic targets by receptors that activated passive ionic conductances. As the list of transmitter substances and their actions expanded, concepts of transmitter actions have broadened and grown more complex to include a variety of intramembranous and intracytoplasmic second messengers that can regulate both active and passive ionic conductances. Present-day research directions center on further expansion of the lists of identified transmitter candidates, and on the more precise characterization of their sites and mechanisms of receptor regulation and transduction. Current research is also illuminating the means by which neurotransmitters act in a coordinated fashion to regulate common synaptic targets. Future directions will likely include new forms of interneuronal, intraneuronal, and glial signals, including lipids, steroids, and as-yet-undiscovered superfamilies of peptides and receptors. Although recent advances in understanding specific transmitters have been achieved largely through in vitro electrophysiological analyses, it is hoped that future research will recast these events in the context of the intact functioning brain. Neurotransmitters are likely to remain a productive focus of future research. PMID- 2891579 TI - Cross-dependence to opioid and alpha 2-adrenergic receptor agonists in NG108-15 cells. AB - Clonidine, a partial alpha 2-agonist, has been used empirically to alleviate opiate withdrawal symptoms, but the mechanism of its effects is not completely understood. We studied the interactions of opioid and adrenergic receptor agonists in the NG108-15 cells, which are a model of opiate dependence. We determined that in these cells the adenylate cyclase (AC) [EC 4.6.1.1; ATP pyrophosphate-lyase (cyclizing) overshoot response to opioid or alpha 2-agonist withdrawal can be significantly attenuated or suppressed by the other agonist. Subsequently, the AC overshoot response can be triggered with the antagonist to the second agonist to which the cells were not dependent. These results demonstrate that convergent dependence to morphine and alpha 2 agonists can occur in a homogeneous cell population without neuronal loops. Therefore, the basic mechanisms that can account for convergent dependence in this model take place at the level of intracellular regulatory pathways that do not require neuronal networks. PMID- 2891580 TI - [Treatment of gastroesophageal reflux: analysis of randomized double-blind trials]. AB - The aim of this study was to analyze the results and the quality of methodology of 51 controlled double blind trials in the medical treatment of gastroesophageal reflux. The results of H2 receptor antagonist treatment were evaluated by the pooling method. Evaluation of methodology was carried out by using a special form filled in by two independent observers. The major criticisms in methodology were: small sample size, unblind evaluation of end-points, inappropriate statistical tests for small samples, and inaccurate handling of the withdrawals. There were only two trials concerning antacids versus placebo: one showed that Novaluzid improved symptoms and another that Maalox did not differ from placebo. The effectiveness of alginic acid and domperidone on either symptoms or endoscopic lesions was not demonstrated. Metoclopramide and bethanechol produced significant relief of reflux symptoms. Sucralfate and bethanechol were better than placebo in improvement of esophagitis endoscopic lesions. The H2-inhibitors efficiently relieved symptoms and esophagitis. Pooling analysis showed that H2-inhibitors were superior to placebo in the healing of esophagitis; the odds ratios were 2.5 for cimetidine and 3.3 for ranitidine, without significant difference. Omeprazole was better than ranitidine in relief of symptoms and esophagitis. The comparison of cimetidine alone with cimetidine plus metoclopramide showed that combined therapy was better in one trial out of two. New controlled trials are necessary to compare these different drugs and their association. PMID- 2891581 TI - [Is gamma-glutamyl transpeptidase constantly normal in benign recurrent cholestasis?]. PMID- 2891582 TI - Interactions of aromatic amino acids with gastric secretagogues in humans. AB - To determine the interactions of phenylalanine and tryptophan with gastric secretagogues, acid secretory studies were performed in 10 healthy subjects. Phenylalanine and tryptophan potentiated the gastric secretory responses following low doses of pentagastrin, whereas their effects on acid secretion stimulated by low doses of histamine or the cholinergic bethanecol were additive. Phenylalanine and tryptophan did not increase maximal acid output stimulated by pentagastrin, histamine, or bethanecol. Doses of the H2-receptor antagonist ranitidine, the prostaglandin E1 analogue misoprostol, atropine, and somatostatin that produced approximately 50% inhibition of pentagastrin-stimulated acid secretion significantly inhibited phenylalanine- and tryptophan-stimulated acid secretion. After the combination of either phenylalanine or tryptophan with pentagastrin, the H2-receptor antagonist significantly inhibited gastric acid secretion, whereas somatostatin, atropine, and the prostaglandin E1 analogue were not effective. These results indicate that both phenylalanine and tryptophan potentiate gastric acid secretion stimulated by a submaximal dose of pentagastrin, whereas their effects on histamine- and bethanecol-stimulated secretion are additive. The potentiating effects of phenylalanine and tryptophan on pentagastrin-stimulated acid secretion depend, at least in part, on intact histamine pathways. PMID- 2891583 TI - Successful treatment of idiopathic secretory diarrhea of infancy with the somatostatin analogue SMS 201-995. AB - The somatostatin analogue SMS 201-995 has been reported to be effective in treating adult secretory diarrhea due to vasoactive intestinal polypeptidoma. We report the effectiveness of this drug in treating severe refractory secretory diarrhea of uncertain etiology in an infant. The patient developed diarrhea within the first few days of life, with mean stool output of 250 ml/kg.day (expected 10 ml/kg.day). Small bowel biopsy showed mild focal enteritis. Serum levels of known gastrointestinal secretagogues were normal. No tumor was detected. Diarrhea was not adequately controlled by various drug treatments. Addition of subcutaneous SMS 201-995 produced a significant sustained decrease in stool output to 80-100 ml/kg.day. During SMS 201-995 treatment, no metabolic, hormonal, or growth abnormalities were noted. SMS 201-995 was discontinued after 9 mo because of patient irritability. Stool output rose immediately to 173 ml/kg.day, and remained stable for 6 mo. It is concluded that SMS 201-995 was a safe and effective treatment in this single childhood case of severe idiopathic secretory diarrhea. PMID- 2891584 TI - Regulation of gastric somatostatin secretion in the mouse by luminal acidity: a local feedback mechanism. AB - The present study was designed to determine whether somatostatin secretion induced by histamine or pentagastrin in the isolated luminally perfused mouse stomach was a direct effect of the secretagogues on gastric somatostatin cells or an indirect effect mediated by the increase in luminal acidity. Perfusion of the lumen with exogenous acid (80-480 nmol/min) caused an increase in somatostatin secretion in proportion to the increase in luminal acidity. The increase in somatostatin secretion was resistant to tetrodotoxin and attained maximal levels (61.6% +/- 8.7% above basal level) similar to those elicited by maximal doses of secretagogues. Conversely, neutralization of basal acid secretion with bicarbonate (20-160 nmol/min) caused a decrease in somatostatin secretion in proportion to the decrease in luminal acidity. Similarly, neutralization of the secretagogue-induced increments in acid secretion with bicarbonate or inhibition of the increments with cimetidine abolished the corresponding increments in somatostatin secretion. It is proposed that acid-induced release of somatostatin in proximity to parietal cells serves as a negative feedback mechanism restraining acid secretion. PMID- 2891585 TI - Age-related differences in receptors for Escherichia coli heat-stable enterotoxin in the small and large intestine of children. AB - Escherichia coli that produce heat-stable enterotoxin are a worldwide cause of diarrheal disease, especially in children. We examined small and large intestinal specimens from children of various ages for the presence of E. coli heat-stable entero-toxin receptors and determined whether the number of receptors or the binding affinity of these receptors was related to the age of the child. We observed specific binding of 125I-heat-stable enterotoxin to all small intestinal and colonic specimens. However, a greater number of receptors per microgram of membrane protein were present in infants and the number of receptors rapidly decreased with increasing age. We also observed that increased heat-stable enterotoxin stimulation of guanylate cyclase was correlated with increased receptor density. We suggest that a greater number of gastrointestinal receptors for heat-stable enterotoxin, capable of activating more guanylate cyclase, may contribute to the increased severity of diarrhea noted in young children exposed to enterotoxigenic E. coli. PMID- 2891586 TI - Somatostatin may not be a hormonal messenger of fat-induced inhibition of gastric functions. AB - The present study was designed to evaluate somatostatin as a hormonal inhibitor of gastric functions in humans. Seven healthy volunteers were investigated on 6 separate days. Peptone meal-stimulated gastric acid secretion was measured by intragastric titration for 2 h and gastric emptying was estimated with a dye dilution technique. The effect of intravenous administration of somatostatin at 0, 12.5, 50, 100, and 200 pmol/kg.h was investigated and related to the effect of intragastric administration of 100 ml of vegetable oil. Plasma somatostatinlike immunoreactivity was elevated during intravenous administration of somatostatin at 100 and 200 pmol/kg.h, whereas no increase was detected in response to the oil. Somatostatin infusion at 100 and 200 pmol/kg.h significantly inhibited the acid secretion by 25% and 65%, and the oil reduced the acid output by 41%. Somatostatin at 100 and 200 pmol/kg.h significantly enhanced gastric emptying, whereas the oil inhibited gastric emptying. These observations suggest that somatostatin may not be an important hormonal messenger of fat-induced inhibition of acid secretion or gastric emptying. PMID- 2891587 TI - Immunoglobulin A in the diagnosis of alcoholic liver disease. AB - The diagnostic relevance of the serum immunoglobulin A (IgA) concentration and liver deposition of IgA for chronic excessive alcohol consumption was evaluated in 164 patients with biochemical liver abnormalities. A relationship was demonstrated between the amount of daily alcohol consumption and the two IgA parameters and serum gamma-glutamyl transpeptidase. A continuous pattern of IgA deposition along hepatic sinusoids proved to be the best diagnostic feature, combining a specificity of 0.91 with a sensitivity of 0.75. Although serum IgA has a specificity of 0.78, its diagnostic value is restricted by a sensitivity of 0.50, making it not superior to serum gamma-glutamyl transpeptidase. Furthermore, serum IgA proved to be related to liver histopathology. High levels of serum IgA are found in hepatitis and cirrhosis, without significant differences between alcoholic and nonalcoholic patients. However, in the case of mild histopathologic changes in the liver, such as steatosis and fibrosis, significantly higher serum IgA concentrations are found in alcoholic than in nonalcoholic liver disease. PMID- 2891588 TI - Effects of recA mutations on pilus antigenic variation and phase transitions in Neisseria gonorrhoeae. AB - Intragenic recombination between the single complete pilin gene (expression locus) and multiple, distinct, partial pilin gene copies (silent, storage loci) is thought to account for the generation of pilus antigenic diversity and piliation phase (on-off) changes exhibited by Neisseria gonorrhoeae. The mechanisms operating in the genomic rearrangements associated with these forms of pilus variation were investigated through the study of isogenic strains of gonococci bearing either wild-type or altered recA alleles. Examination of the rates of pilus phase variation and the genetic basis for changes in piliation status displayed by these strains show that recA mediated homologous recombination is required for these high frequency events and confirm that the nonpiliated state results from mutations in the expressed pilin gene. In a strain that is deficient in recA mediated homologous recombination, pilus phase variation occurs at a 100-1000-fold reduced rate and results predominantly from one class of spontaneous frameshift mutations within the pilin structural gene. PMID- 2891589 TI - Updated use of digitalis and nitrates in the elderly. AB - Myocardial ischemia may be produced by a wide variety of pathophysiologic scenarios. Currently, long-acting nitrates, beta blockers, and calcium blocking drugs are available to treat ischemia. Each class of therapy poses potential problems for the elderly, and therapy must be individualized. Long-acting nitrates are probably not the best choice of monotherapy since tolerance develops to their use over time. Congestive heart failure, a common sequela to myocardial infarction, is currently best treated by diuretics and vasodilating drugs. These therapies are generally well-tolerated by the elderly. Digitalis, which is not easily given to the elderly due to potential toxicity, is probably best avoided in this patient group unless needed to treat arrhythmia. Careful differential diagnosis of congestive heart failure is a critical pre-condition to starting any therapy for heart failure, particularly in the elderly patient. PMID- 2891591 TI - Dipeptidyl peptidase IV activity in cells of T-lymphoid origin is decreased in cultures with 12-0-tetradecanoylphorbol-13-acetate (TPA). AB - Dipeptidyl peptidase IV (DPP IV) is a specific enzyme for cells of T-lymphocytic lineage. It has been attempted to induce DPP IV activity in DPP IV negative T lymphoid leukaemias by 12-o-tetradecanoylphrobol-13-acetate (TPA). Isolated cells from peripheral blood of 6 healthy blood donors and 22 patients with various types of leukaemia were cultivated in RPMI-1640 medium with 20% fetal calf serum alone (control) or supplemented with 20% human placenta conditioned medium (HPCM) or with 16 nmol/l TPA for 3 days. The percentage of DPP IV positive lymphocytes from blood donors remained unchanged in control and HPCM cultures, but decreased significantly in TPA cultures. Leukemic cells from three DPP IV positive cases of acute T-lymphoblastic leukaemia (T-ALL) reacted to the TPA treatment in a similar manner. Leukaemic cells of two DPP IV negative T-ALL cases remained negative in all three types of cultures, thus no induction of DPP IV activity was found. Other normal blood cells as well as leukaemic cells of 7 null-ALL, 1 preB-ALL, 3 B-CLL and 6 AML patients were DPP IV negative before and after cultivation in all types of culture. These findings showed that DPP IV is specifically expressed in cells of T-lymphocytic lineage even after short-term cultivation. HPCM was found to have no effect on DPP IV activity in T-lymphoid cells. PMID- 2891590 TI - [Role of glutamic acid in preserving ATP in the human myocardium during cardioplegia]. PMID- 2891592 TI - A new family with congenital factor XIII deficiency showing a deficit of both subunit A and B. Type I factor XIII deficiency. AB - In this study we present a new case of Factor XIII deficiency. The proposita, a 34 year old woman, showed a deficiency of both subunit a and subunit b, and a moderate bleeding tendency. Because of the concomitant decrease of subunits a and b the proposita is considered to be an example of Type I disease. Factor XIII levels were less than 10% both as activity and antigen. Several family members showed intermediate levels of both subunit a and b and were asymptomatic. They were considered to be heterozygotes. The hereditary pattern is autosomal incompletely recessive. Type I disease appears much less frequent than Type II. PMID- 2891593 TI - Characterization of the submerged growth of Moraxella bovis. AB - A submerged batch cultivation of Moraxella bovis in a medium containing enzymic casein hydrolyzate and supplemented with dialyzed ram blood was described. Up to the growth limitation the bacteria grew exponentially without a lag phase and with a doubling period of 64 min. During the exponential phase no significant decrease of viable cells and cell autolysis were observed. Amino acids were the limiting factor. At the end of growth glutamic acid, threonine and serine were detected at the lowest concentrations. Substrate limitation led to an irreversible decrease of the metabolic activity. Growth yield on oxygen was 2.3 X 10(9) cells per mg O2. The fraction of respiration required for growth-uncoupled processes was negligible. During the cultivation ammonia was produced and the pH increased but it was not the inhibitory factor. Respiration was not limited by oxygen at concentrations higher than 0.63 mumol O2 per L. Sufficient pili were produced. PMID- 2891595 TI - [Secondary prevention following myocardial infarct. Which drug treatment is safe today?]. PMID- 2891596 TI - [The brain--an endocrine gland. The classical distinction in neural and humoral control of organ function is no longer tenable]. PMID- 2891594 TI - Physiology of a wild strain and high yielding mutants of Streptomyces rimosus, producing oxytetracycline. AB - A wild-type Streptomyces strain, yielding 1 g/L of oxytetracycline was compared with mutants giving up to 7 g/L, using complex media in stirred and shaken culture. Increased production of oxytetracycline was associated with high specific production rates and a longer production period. The superiority of the mutants was associated with changes in morphological behaviour during growth in submerged culture, and in their patterns of growth and respiration, coupled with increased resistance to the product. The productivity of the mutants was sensitive to the rate of stirring, the type of calcium carbonate used in the medium and the type of inoculum. Careful control of these factors was necessary to obtain high yields of oxytetracycline. With the exception of acetyl-CoA carboxylase, the levels of enzymes measured and of amounts of adenylates in the mycelium did not appear to be related to the degree of antibiotic production. PMID- 2891597 TI - [Pharmacological characterization of chicken cardiac beta-adrenoceptors]. AB - Pharmacological properties of cardiac beta-adrenoceptors of embryonic chick (16 18 day in ovo), hatched chick (3-5 days after hatching) and adult chicken (20 weeks after hatching) were investigated. Pharmacological analysis using subtype specific agonists and antagonists showed that cardiac beta-adrenoceptors of embryonic chick and hatched chick could not be classified as beta 1- or beta 2 adrenoceptors. Scatchard analysis of specific [125I]-iodocyanopindolol (ICYP) binding revealed ICYP bound to two different population of binding sites (high and low affinity) in all stages; Kd and Bmax of these sites remained unchanged before and after hatching, although Bmax but not Kd was found to increase in adult chicken. Displacement of ICYP with propranolol (a nonspecific beta antagonist), ICI 118,551 (a specific beta 2-antagonist) and atenolol (a specific beta 1-antagonist) indicated the presence of two affinity binding sites for all of the antagonists. Ki values for these antagonists at the high affinity binding sites were almost identical to pA2 values obtained from their antagonistic effects on isoproterenol inotropic response, suggesting that the high affinity binding sites for ICYP bear the pharmacological significance. Significant increase in sensitivity to the inotropic effects of beta-adrenoceptor agonists was observed in the hatched chick heart, whereas Ki values calculated from displacement of ICYP with these agonists in the presence of GppNHp were not changed. Dobutamine which was a Partial agonist in the embryonic chick heart, was found to behave as a full agonist in the hatched chick heart. These result suggested that chicken cardiac beta-adrenoceptors show different properties from either beta 1- or beta 2-adrenoceptors reported in mammalian hearts, and coupling between binding and adenylate cyclase might be more efficient after hatching. PMID- 2891598 TI - [Structural analysis of the class II gene region of rat MHC (RT1)--a novel beta chain gene mapped to RT1. B region]. AB - In the present study, genomic DNAs obtained from intra-RT1 recombinant rats were subjected to restriction fragment length polymorphism (RELP) analysis, using HLA DP beta cDNA as a probe. Out of 8 strains of rats whose haplotypes were evaluated serologically, 3 strains (NIG-III, LEJ, and DA. 1I (BI)), including 1 congenic strain, had RT1. A/B recombinant haplotypes (RT1. AqB1D1, AuBbDb, and AnBaDa, respectively). After digestion with BglII or HincII, RFLP analysis of these strains with HLA-DP beta probe showed strong bands associated with RT 1. A haplotypes, in addition to some weaker cross-hybridizing bands. That is, after BglII digestion, 4.2kb band was detected associated with RT 1. Aq, 2.1 kb band with A1 and Ab, 4.3 kb band with Au, respectively. After HincII digestion, 1.2 kb band was detected in association with RT1. Aa and 13.0 kb band with An, respectively. From these results I conclude that the recombination events have occurred within the class II region of RT1, especially between B beta gene and a novel class II beta gene which is proposed to be mapped near RT1. A region. The novel gene seems to be a candidate for DP beta-like gene in RT1, because it strongly hybridized with HLA-DP beta cDNA. As in the mouse or the man, a recombinational hotspot might be generated around this novel gene, which provides another evidence for the structural homology among the MHCs of these three species. PMID- 2891599 TI - Effect of insulin-induced hypoglycemia on circulating levels of plasma growth hormone-releasing hormone and somatostatin in children. AB - In response to insulin-induced hypoglycemia (0.1 U insulin/kg body weight, i.v.) plasma levels of growth hormone-releasing hormone (GHRH), somatostatin (SLI), and growth hormone (GH) were measured by radioimmunoassay in 10 children with short stature. Insulin injection resulted in a significant increase in plasma GHRH values at 15 min (10.0 +/- 0.5 vs. 17.1 +/- 3.1 pg/ml; p less than 0.05) preceding the increase in plasma GH levels (1.5 +/- 0.4 vs. 13.6 +/- 1.2 ng/ml; p less than 0.001). SLI concentrations peaked between 15 and 60 min after insulin injection (20.9 +/- 1.2 vs. 47.1 +/- 6.2 pg/ml; p less than 0.01). No correlation was present between plasma GHRH or SLI levels and plasma GH concentrations. A significant negative correlation could be established between maximum increments of plasma GHRH and SLI levels (r = -0.843; p less than 0.01) in response to insulin injection. This finding suggests a possible relationship between these two hormones at peripheral level. PMID- 2891600 TI - Treating tremor induced by lithium. PMID- 2891601 TI - Ultrastructural observations on the cytomegalic inclusion cell in peripheral blood. AB - A 31-year-old woman with adult T-cell leukemia developed interstitial pneumonitis. Large abnormal cells different from those of adult T-cell leukemia appeared in the peripheral blood. Hematoxylin-eosin staining of the buffy coat of peripheral blood revealed these cells to be cytomegalic inclusion cells. Electron microscopy disclosed cytomegalovirus particles in these inclusion cells. Virus particles were seen in both the nuclei and cytoplasm. Dense bodies characteristic of cytomegalovirus infection were also seen in the cytoplasm. This is the first report of cytomegalovirus particles found in the peripheral blood mononuclear cells. PMID- 2891602 TI - Localization at a subband level of polymorphic 13q14 DNA probes for diagnosis of hereditary retinoblastoma and Wilson disease. AB - Two single-copy DNA sequences, pG24E6.8 (D13S21) detecting a low-frequency MspI RFLP and pG14E1.9 (D13S22) detecting a high-frequency Dra I RFLP, have been isolated and cloned from a human chromosome 13-specific phage library and localized at 13q14. Their subband localization was described using a panel of cell lines from patients with different chromosome 13 deletions. A quantitative analysis of hybridization signals was carried out, taking for reference a single copy DNA sequence from another chromosome. D13S21 and D13S22 were both assigned to q14.1-14.2, which also harbors the genes responsible for retinoblastoma and Wilson disease. The Dra I polymorphism detected by pG14E1.9 is a very suitable one for linkage studies in families with either disease. PMID- 2891603 TI - Loss of heterozygosity and the origin of meningioma. AB - In some human tumors, loss of particular genes manifested indirectly by loss of heterozygosity for specific RFLPs seems to uncover either heterozygous deletions leading to a gene doses effect or homozygous deletions due to a silent allele at the corresponding locus, both causing the loss of regulatory functions (antioncogenes, suppressor genes). Meningioma, a benign human tumor derived from the coverings of brain and spinal cord, is associated with complete loss, rarely deletion, of one chromosome 22. About 60% of meningiomas exhibit monosomy 22 in all or part of cells; however, about 40% display a normal karyotype. Comparison of constitutional and tumor genomes from 12 patients showed loss of heterozygosity on 22 in three cases, suggesting the involvement of events at the DNA level. PMID- 2891604 TI - Inherited and de novo deletion of the tyrosine aminotransferase gene locus at 16q22.1----q22.3 in a patient with tyrosinemia type II. AB - Tyrosinemia II is an autosomal-recessively inherited condition caused by deficiency in the liver-specific enzyme tyrosine aminotransferase (TAT; EC 2.6.1.5). We have restudied a patient with typical symptoms of tyrosinemia II who in addition suffers from multiple congenital anomalies including severe mental retardation. Southern blot analysis using a human TAT cDNA probe revealed a complete deletion of both TAT alleles in the patient. Molecular and cytogenetic analysis of the patient and his family showed one deletion to be maternally inherited, extending over at least 27 kb and including the complete TAT structural gene, whereas loss of the second TAT allele results from a small de novo interstitial deletion, del 16 (pter----q22.1::q22.3----qter), in the paternally inherited chromosome 16. Three additional loci previously assigned to 16q22 were studied in our patient: haptoglobin (HP), lecithin: cholesterol acyltransferase (LCAT), and the metallothionein gene cluster MT1,MT2. Of these three markers, only the HP locus was found to be codeleted with the TAT locus on the del(16) chromosome. PMID- 2891605 TI - The study of a French family with two duplicated C4A haplotypes. AB - The finding of two duplicated C4A haplotypes in a normal French family led to a detailed study of their C4 polymorphism. The father had an extremely rare A*6A*11, B*QO haplotype inherited by all of his children and the mother had the more common A*3A*2, B*QO haplotype. Two HLA identical daughters only have four C4A alleles. The father's A11 allotype expresses Ch:1 (Chido) rather than Rg:1 (Rodgers) and represents a new Ch phenotype Ch:1,-2,-3,-4,-5,-6. In order to clarify the genetic background in this unusual family, DNA studies of restriction fragment length polymorphisms (RFLPs) were undertaken. The father's rare haplotype, which expresses two C4A allotypes, results from a long and a short C4 gene normally associated with the A*6, B*1 that also exhibits the Bg/II RFLP. As it travels in an extended MHC haplotype HLA A2, B57(17), C2*C, BF*S, DR7 that is most frequently associated with A*6, B*1, we postulate that the short C4B has been converted in the alpha chain region to a C4A gene which produces a C4A protein. This report of a short C4A gene is the first example in the complex polymorphism of C4. PMID- 2891607 TI - DNA sequence variation within the beta-glucuronidase gene complex among inbred strains of mice. AB - Tightly linked to the gene that encodes murine beta-glucuronidase (GUS) are three GUS-specific regulatory elements. Together, these elements define the GUS gene complex. Specific alleles of each regulatory element are associated with a specific GUS structural allele. These associations define the three common forms (haplotypes) of the GUS gene complex, designated A, B, and H. As an initial step in defining the DNA determinants of each regulatory element and to develop DNA markers for the common haplotypes, we have identified several DNA variants by blot hybridization analysis of restricted genomic DNA using GUS-specific cDNA probes. Of 30 tested restriction endonucleases, 24 reveal DNA polymorphisms that distinguish B- and H-haplotype DNA from that of the A haplotype. Of these 24, 18 uncover a restriction fragment length polymorphism in which the polymorphic fragment of A-haplotype DNA is 200-300 bp larger than the corresponding fragment of B- or H-haplotype DNA. DNA sequence analysis of this polymorphic region reveals the presence of a short, interspersed repetitive element of the B2 family within A-haplotype DNA which is absent in DNAs of B- or H-haplotype mice. None of the DNA variations revealed by these analyses can be associated at this time with variation in the regulatory or structural properties of GUS among the common haplotypes. Nevertheless, they do provide useful haplotype-specific markers within the GUS gene complex which are of critical importance for DNA transfer experiments in transgenic mice and in cultured cells. PMID- 2891608 TI - Sequence analysis of the murine Hox-2.2, -2.3, and -2.4 homeo boxes: evolutionary and structural comparisons. AB - We have determined the nucleotide sequences and deduced the amino acid sequences of three tandemly arranged murine boxes of the Hox-2 homeo box gene complex on mouse chromosome 11 (Hox-2.2, -2.3, and -2.4). The type and position of differences with other sequenced homeo boxes were analyzed. Hox-2.2 is nearly identical with its cognate human homeo box Hu-2. Hox-2.3 shares 59 of 61 amino acids with the Antennapedia homeo domain of Drosophila and the MM-3 homeo domain of Xenopus and shows 60 of 61 amino acid identity with human HuC1. Hox-2.3, MM-3, and HuC1 also share a stretch of six glutamic acid residues followed by a stop codon 15-20 amino acids 3' of the homeo domain. Hox-2.4 is relatively divergent from most of the other homeo boxes sequenced to date; however, it matches the Hox 3.1 murine homeo domain at 60 of 61 positions. Sequence comparisons with other murine homeo domains, together with previous studies of their genomic organization and chromosomal location, provide support for the hypothesis of a large-scale duplication resulting in the two major murine homeo box gene complexes Hox-1 and Hox-2. PMID- 2891606 TI - Familial deletion of Xp21.2 with glycerol kinase deficiency and congenital adrenal hypoplasia. AB - Congenital adrenal hypoplasia (CAH) and glycerol kinase deficiency (GKD) were diagnosed in a male during the neonatal period. On prometaphase chromosomes there was an interstitial deletion involving Xp21.2 and possibly Xp21.3 in the propositus and his mother. Duchenne muscular dystrophy (DMD) was excluded on the basis of normal serum creatine kinase and a muscle biopsy. Molecular hybridization of DNA from the propositus with 11 probes covering Xp21, including the DMD locus, was normal. In situ hybridization with the probe pERT87.15 showed a normal signal at the expected site indicating that the DMD locus was preserved and not translocated. This suggests that the DMD locus is located at the most proximal part of the sub-band Xp21.2 or in Xp21.1, and that the DXS68 (probe L1) is far from it on the distal flanking DNA. PMID- 2891609 TI - ECG studies with astemizole. AB - 1 Six healthy volunteers took part in a 2-week haemodynamic safety study of astemizole. 2 They were given 30 mg daily (3 X 10 mg tablets) for the first 3 days and 10 mg daily for the next 12 consecutive days. 3 Heart rate, blood pressure, ECG and systolic time intervals at rest were measured before the start and five times during the day. 4 No changes were observed in any of the parameters measured. The configuration of the ECG was not influenced. 5 Serum concentrations of astemizole plus hydroxylated metabolites measured at the end of the study were 16 times lower than those detected in a patient overdosing on 200 mg astemizole. PMID- 2891610 TI - Characterization of the MHC class II region in cattle. The number of DQ genes varies between haplotypes. AB - The organization of the major histocompatibility complex (MHC) class II region in cattle was investigated by Southern blot analysis using human probes corresponding to DO, DP, DQ, and DR genes. Exon-specific probes were also employed to facilitate the assessment of the number of different bovine class II genes. The results indicated the presence of single DO beta and DR alpha genes, at least three DR beta genes, while the number of DQ genes was found to vary between MHC haplotypes. Four DQ haplotypes, DQ alpha 1 beta 1 to DQ alpha 2 beta 4, possessed a single DQ alpha and a single DQ beta gene whereas both these genes were duplicated in eight other haplotypes, DQ alpha 3 beta 5 to DQ alpha 9 beta 12. No firm evidence for the presence of bovine DP genes was obtained. The same human probes were also used to investigate the genetic polymorphism of bovine class II genes. DQ alpha, DQ beta, DR alpha, DR beta, and DO beta restriction fragment length polymorphisms (RFLPs) were resolved and in particular the DQ restriction fragment patterns were highly polymorphic. Comparison of the present result with the current knowledge of the class II region in other mammalian species suggested that the DO, DP, DQ, DR, and DZ subdivision of the class II region was established already in the ancestor of mammals. The DP genes appear to be the least conserved class II genes among mammalian species and may have been lost in cattle. The degree of polymorphism of different class II genes, as revealed by RFLP analyses, shows striking similarities between species. PMID- 2891611 TI - Diversity of the mouse T cell receptor C gamma 1 gene: structural analysis in C57BL/Ka. AB - We have isolated an unusual T cell receptor gamma chain cDNA clone (gamma 7.1) from a library made from RNA derived from adult thymus of C57BL/Ka mice. This cDNA clone corresponds to the appropriately processed C gamma 1 constant region exons preceded by 1.5 kb of J-C gamma 1 intron. The gamma 7.1 coding region is extremely homologous to the C gamma 1 gene of BALB/c mice, differing at the protein level by a single deletion (alanine 139) and a single substitution. This latter change eliminates the sole N-linked sugar attachment site, providing a basis for strain-specific glycosylation patterns. The J-C gamma 1 intronic region contains two DNA segments (termed psi J gamma 1 and psi J gamma 2) that are highly reminiscent of joining (J) segments; both have potentially functional recombination and donor splice sequences flanking an open reading frame. Northern analysis suggests that gamma 7.1 may be derived from a large, variable region containing precursor. PMID- 2891612 TI - Extensive genomic polymorphism in mouse 21-hydroxylase region. PMID- 2891613 TI - Taq I-generated HLA-DQ alpha polymorphism in Japanese patients with narcolepsy. AB - Taq I-generated HLA-DQ alpha restriction fragment length polymorphism was examined in Japanese patients with narcolepsy. All patients were DR2 positive and shared a 6.0 kb fragment, although this fragment was found only in 54% of the healthy DR2-positive Japanese. This finding added the DQ alpha gene to the list of candidates for the possible narcolepsy-susceptibility gene. In contrast, there was no complete association between narcolepsy and DX alpha restriction fragment length polymorphism. These findings suggest that a narcolepsy-susceptibility gene is located closer to the DQ locus than to the DX locus. PMID- 2891614 TI - The same MHC recombinational hot spots are active in crossing-over between wild/wild and wild/inbred mouse chromosomes. AB - Four recombinational breakpoints were mapped in the K-A interval of the mouse major histocompatibility complex (MHC) by Southern blot analysis. The breakpoint in B10.SBR, containing a b/s recombinant MHC haplotype, is located about 45 kb upstream of the A beta 2 gene close to the breakpoint in B10.AQR. Crossover in two cas3/cas4 and one cas4/cas3 recombinant haplotypes has taken place in the previously identified K/A beta 3 and A beta 3/A beta 2 recombinational hot spots. The same hot spots are thus active in crossover between two Mus musculus castaneus MHC haplotypes and in crossover between a laboratory and a M. m. castaneus MHC haplotype. PMID- 2891615 TI - Mitogenic effect of polyclonal anti-porcine lymphocyte E-receptor antiserum IgG. AB - In the present paper we report the mitogenic effect of the sheep anti-porcine lymphocyte E-receptor antiserum IgG(APERIgG) on porcine peripheral T-lymphocytes in vitro. The effect was apparently dose-dependent and not seen in the B lymphocyte cultures. Kinetic study showed that the maximal 3H-thymidine incorporation, similar to that induced by Con A, occurred on the third day of incubation. Neither F(ab')2 nor Fab fragment of APERIgG was able to induce cell proliferation, indicating that the integrity of IgG molecule was essential for cell response. It was very interesting to note that though there is cross antigenicity between porcine and human E-receptors, no similar effect could be produced by APERIgG in human peripheral lymphocyte cultures under the same experimental conditions, suggesting the existence of minor difference in structure between the porcine and human E-receptors. PMID- 2891616 TI - Maternal immunization with P fimbriae for the prevention of neonatal pyelonephritis. AB - Rhesus monkeys (Macaca mulatta) were immunized with purified P fimbriae from Escherichia coli during the last trimester of pregnancy. Infants born of these mothers were compared with those from nonimmunized rhesus mothers. A delay in the onset of renal disease after bladder infection showed protection from passive immunization. This was associated with a high antibody titer in serum. In addition to delayed onset of renal infection, a decreased number of immunized monkeys developed pyelonephritis. PMID- 2891617 TI - Characterization of monoclonal antibodies to fimbria-associated adhesins of Bacteroides loescheii PK1295. AB - Bacteroides loescheii PK1295 fimbriae, which mediate the lactose-sensitive coaggregation with Streptococcus sanguis 34 and the lactose-insensitive coaggregation with Actinomyces israelii PK14, were injected into mice to raise adhesin-specific monoclonal antibodies (MAbs). Supernatants of hybridomas were screened for the capacity to inhibit coaggregation and agglutinate intact bacteria. Of the 10 MAbs that were isolated, 4 were specific and potent inhibitors of the coaggregation between B. loescheii and S. sanguis and two other MAbs specifically inhibited the B. loescheii-A. israelii interaction. None of the six MAbs which inhibited adherence were capable of agglutinating whole cells of B. loescheii, whereas the four remaining MAbs agglutinated whole cells but had no effect on coaggregation. Fab fragments of two MAbs, one that inhibited the coaggregation with S. sanguis and another that inhibited the interaction with A. israelii, also were shown to inhibit the respective coaggregation interactions, suggesting that each of the immunoglobulins recognized its adhesin molecule at or near the active sites. By immunoblotting or immunoprecipitation, the S. sanguis adhesin-specific MAbs reacted with a 75-kilodalton polypeptide present in fimbria enriched preparations, whereas the A. israelii adhesin-specific MAbs recognized a 45-kilodalton polypeptide in the same preparations. By screening hybridoma supernatants directly for their capacity to block coaggregation, we isolated MAbs which were used to establish that the B. loescheii-S. sanguis and the B. loescheii-A. israelii interactions were mediated by different adhesins. PMID- 2891618 TI - Virulence properties of enterotoxigenic Escherichia coli O8: KX105 strains isolated from diarrheic piglets. AB - Twenty-two enterotoxigenic Escherichia coli (ETEC) O8:KX105 strains isolated from 1- to 7-week-old diarrheic piglets were examined for virulence properties. Thirteen strains caused acute watery diarrhea in orally infected, colostrum deprived newborn piglets, whereas the remaining nine did not. The enteropathogenic strains colonized the small intestine, albeit with lower intensity than classical porcine ETEC. They produced the heat-stable STb and heat labile LT enterotoxins, whereas the nonenteropathogenic strains produced the STb enterotoxin alone. None of the E. coli O8:KX105 strains exhibited mannose resistant hemagglutination with erythrocytes from 12 species. Ten of the enteropathogenic and two of the nonenteropathogenic strains were positive for mannose-sensitive hemagglutination. These strains produced rodlike fimbriae 3 to 5 nm in diameter, whereas no fimbriae were detected on the other strains. None of the 22 strains produced the fimbrial antigens F4, F5, F41, F2, F3, FY(Att 25), and F165. Of the 13 enteropathogenic strains, 10 expressed the F6 antigen in the intestines of infected piglets but not in cultures. The other three enteropathogenic strains apparently lacked all of the known fimbrial antigens from porcine ETEC. PMID- 2891619 TI - Stimulation of superoxide and lactoferrin release from polymorphonuclear leukocytes by the type 2 fimbrial lectin of Actinomyces viscosus T14V. AB - Polymorphonuclear leukocyte (PMN)-dependent destruction of Actinomyces viscosus T14V is initiated by the recognition of galactose-containing receptors on sialidase-treated PMNs by the lectin associated with the type 2 fimbriae of these bacteria. A. viscosus T14V also stimulates the respiratory burst in PMNs as well as the release of contents of the secondary granules, as determined by the presence of lactoferrin in the culture supernatants. Under the experimental conditions employed, these bacteria do not induce the release of beta glucuronidase, a constituent of primary granules. None of the three PMN responses studied occurs in cultures containing a mutant of A. viscosus T14V that lacks fimbriae. Activation of the PMNs is mediated by the lectin associated with the type 2 fimbriae, as demonstrated by the finding that beta-linked galactosides inhibit stimulation of the respiratory burst. Thus, the interaction of the Actinomyces fimbrial lectin with its complementary receptors on PMNs results not only in killing of these bacteria but also in the release of reactive oxygen intermediates and enzymes that may be detrimental to surrounding host tissues. PMID- 2891620 TI - Bacteroides gingivalis fimbriae stimulate production of thymocyte-activating factor by human gingival fibroblasts. AB - In a previous report (Y. Ohmori, S. Hanazawa, S. Amano, T. Miyoshi, K. Hirose, and S. Kitano, infect. Immun. 55:947-954, 1987), we showed that human gingival fibroblasts spontaneously produce thymocyte-activating factor (FTAF), which stimulates mitogen-induced thymocyte proliferation. In the present study, we examined the effect of Bacteroides gingivalis fimbriae on FTAF production by the cells, because the fimbriae may be involved in attachment of the organism to periodontal tissues. We show here that the fimbriae bind to the cells, which may subsequently lead to the stimulation of FTAF production by the cells. PMID- 2891621 TI - Influence of hCG treatment on the metabolism of progesterone and pregnenolone in vitro by the human undescended prepubertal testis. AB - Testicular biopsies were taken from 56 prepubertal and pubertal boys, aged 3-17 years, with undescended testes. The biopsies were incubated in vitro with 3H progesterone or 3H-pregnenolone. Fifteen of the boys had been treated with human chorionic gonadotrophin (hCG) prior to operation. Nine boys were operated on within 1 week of the last injection of hCG while the others were operated on between 12 days and 2 years after hCG treatment. In non-treated prepubertal boys very small amounts of substrate were converted by means of the enzymes 3 beta hydroxysteroid-dehydrogenase and 17 alpha-hydroxylase and virtually no testosterone was produced. Immediately after treatment with hCG there was a large increase in the conversion of substrate by 17 alpha-hydroxylase and 3 beta hydroxysteroid-dehydrogenase. Considerable amounts of testosterone were formed, especially from pregnenolone, while smaller amounts were formed from progesterone. This suggests that testosterone production occurred primarily via the delta 5 pathway, at least beyond the 17 alpha-hydroxylase-step. Within 2 weeks of the last hCG injection, steroidogenic activity had decreased towards levels similar to those found in prepubertal testis from untreated boys. These observations indicate that hCG treatment of boys with undescended testes does not result in irreversible or even long-lasting stimulation of their steroidogenic function. PMID- 2891622 TI - Changes in the secretion of ABP into testicular interstitial fluid with age and in situations of impaired spermatogenesis. AB - Androgen-binding protein (ABP) was measured in serum and testicular interstitial fluid (IF) from rats during sexual maturation or in adult rats in which impairment of spermatogenesis had been induced by (i) testosterone withdrawal following Leydig cell destruction, (ii) local heating (43 degrees C) of the testes for 30 min or (iii) induction of unilateral cryptorchidism (UCD). The changes observed were related to the IF levels of testosterone and, in most instances, to the serum levels of FSH. The levels of ABP in serum and IF decreased together with age, being highest at 30 days, falling steeply by 40 days and then slowly but progressively up to 100 days of age. A similar pattern was observed for serum FSH, except that the initial fall occurred beyond 40 days of age. Treatment with EDS or exposure to local heating caused comparable reductions in testicular weight (25-30% by 7 days after treatment, 50% by 21-28 days) and raised the serum levels of FSH. In both groups the levels of ABP in IF were increased by two- to three-fold while the levels of testosterone were either reduced markedly (EDS-treatment) or remained unchanged (local heating). In rats made UCD for 60 days, the weight of the abdominal testis was reduced by 75%, compared with the contralateral scrotal testis, while the IF levels of ABP and testosterone were significantly increased (55%) and decreased (90%), respectively. Short-term (3 days) deprivation of testosterone in adult rats, following immunoneutralization of LH, was without significant effect on IF levels of ABP. It is concluded that ABP secretion into IF is increased in situations of subnormal (or sub-adult) numbers of germ cells and this is usually associated with high levels of FSH. Measurement of ABP levels in IF should prove of value for the monitoring of Sertoli cell function in vivo and may be of diagnostic use for the detection of changes in germ cell numbers. PMID- 2891623 TI - Cooling prevents ischaemic testicular damage after spermatic cord clamping in rats. AB - A controlled trial was conducted on four groups of seven rats to evaluate any beneficial effect of cooling to 15 degrees C on testicular ischaemia induced by clamping of the spermatic cord for 2, 4, 6 or 8 h. At operation the microscopic appearance of the testes on unclamping was a poor guide to ultimate viability, whereas by the third day macroscopic and microscopic appearances concurred. When killed on the third day, testicular histology demonstrated that increasing periods of clamping led to gross ischaemia and infarction when testes were maintained at 37 degrees C, and this was reduced greatly by testicular cooling. For each period of clamping, maintenance of spermatogenesis, expressed in terms of Johnsen's histological scores, was significant (P less than 0.01), being 2 (37 degrees C) vs 5.3 (15 degrees C) for 8-h clamping. It is proposed that testicular cooling should be used during autotransplantation of testes in humans. PMID- 2891624 TI - Epidemiological features of HTLV-I carriers and incidence of ATL in an ATL endemic island: a report of the community-based co-operative study in Tsushima, Japan. AB - To extend the epidemiological study on adult T-cell leukemia-lymphoma (ATL) in Japan, the geographical and demographic characteristics of carriers of human T lymphotropic virus type I (HTLV-I) and patients with ATL were analyzed in Tsushima Island, which is one of the typical endemic areas of ATL in Kyushu, Japan. Even on the small island of Tsushima (710 km2; pop. 48,875; 123 villages), the positive rates of anti-HTLV-I antibody among the 58 villages studied varied from 2% to 50%, a fact that is probably associated with the historical events affecting the movement of the indigenous population of Tsushima Island. The positive rate of anti-HTLV-I antibody in males increased little with age; however, the female rate increased distinctly with age in moderate and high HTLV I-endemic villages where more than 15% of the inhabitants had positive anti-HTLV I antibody. Analysis of anti-HTLV-I antibody positivity between spouses confirmed that HTLV-I was more contagious from husband to wife than from wife to husband, which corresponded to the fact that the positive rate of anti-HTLV-I antibody in females older than 30 years was higher than that in males. Recently the rate of carrier children from HTLV-I carrier mothers was estimated at around 20%. The recent annual incidence rates of ATL among 1,000 HTLV-I carriers older than 40 years living in Tsushima Island was estimated at 2.2 in males, 0.8 in females. PMID- 2891625 TI - Mother-to-child transmission of human T-cell leukemia virus type I (HTLV-I): a fifteen-year follow-up study in Okinawa, Japan. AB - Okinawa prefecture is one of the endemic areas for adult T-cell leukemia/lymphoma (ATLL) in Japan. In this study, 2,013 serum specimens drawn serially over a period of 15 years (1968-1983) from 311 mother/child pairs in Okinawa were tested for antibodies to human T-cell leukemia virus type I (HTLV-I) by enzyme-linked immunosorbent assay and by indirect immunofluorescence. The prevalence rate of HTLV-I antibodies was 20.9% (65 cases) in the mothers and 3.2% (10 cases) in the children. Of the 65 seropositive mothers, 10 (15.4%) had seropositive children. This study revealed a significant difference between the prevalence rates of HTLV I antibodies in mothers and children. In addition, children born to seropositive mothers had acquired their HTLV-I antibodies by the age of 3 years, and were still seropositive at the age of 18 years. No initially seronegative child was found to have seroconverted during the period investigated. PMID- 2891626 TI - Transplacental induction of a specific mutation in fetal Ha-ras and its critical role in post-natal carcinogenesis. AB - Mouse skin tumors were produced after transplacental initiation [with 7,12 dimethylbenz(a)anthracene], only when the skin was treated post-natally with a tumor-promoting agent (12-O-tetradecanoyl phorbol 13-acetate). DNA analysis of tumors showed that all carcinomas analyzed contained a specific mutation (A to T transversion) at the 61st codon of c-Ha-ras. Fifty per cent of the papillomas analyzed also had this same mutation. The A to T transversion at the 61st codon of Ha-ras was heterozygous in all positive papillomas and carcinomas. No such mutation was found when benzo(a)pyrene was used as an initiating agent. These results indicate that fetal c-Ha-ras can be transplacentally activated through a specific point mutation by a carcinogen, but a cell harboring such a mutation may remain dormant until it encounters a tumor-promoting stimulus. PMID- 2891627 TI - Melphalan-induced appearance of potent antitumor immune reactivity in tumor bearer lymphocytes co-expressing the Lyt 2 and the L3T4 antigens. AB - We have previously shown that Sephadex G-10-adherent spleen cells from mice bearing a large MOPC-315 tumor can suppress the in vitro generation of a primary anti-MOPC-315 cytotoxic response. Here we show that following low dose melphalan (L-phenylalanine mustard; L-PAM) therapy of such tumor bearing mice their Sephadex G-10-adherent spleen cells no longer suppressed but actually brought about the generation of enhanced antitumor cytotoxicity when added to the immunization culture of normal spleen cells and MOPC-315 tumor cells. This immunopotentiating activity of the Sephadex G-10-adherent spleen cells from L-PAM treated MOPC-315 tumor bearers was attributed to T-cells which co-express the Lyt 2 and the L3T4 antigens based on results of experiments employing negative selection. Specifically, depletion of Lyt 2+ cells or of L3T4+ cells abolished the ability of the Sephadex G-10-adherent splenic cell population from L-PAM treated MOPC-315 tumor bearers to bring about the generation of enhanced antitumor cytotoxicity when added to the immunization culture of normal spleen cells. Moreover, the immunopotentiating activity was not restored when a population of Sephadex G-10-adherent spleen cells depleted of Lyt 2+ cells was admixed with a population of Sephadex G-10-adherent spleen cells depleted of L3T4+ cells. In light of the unusual phenotype of the immunopotentiating cells in the spleens of L-PAM treated MOPC-315 tumor bearing mice (i.e. Lyt 2+ L3T4+), and since the vast majority of thymocytes in normal adult BALB/c mice co-express the Lyt 2 and the L3T4 antigens, we evaluated the effect of low dose L-PAM therapy on the antitumor immune reactivity of thymocytes from MOPC-315 tumor bearing mice. A low dose of L-PAM was found to render thymocytes from MOPC-315 tumor bearers, but not from normal mice, capable of bringing about the generation of enhanced lytic activity when added to the immunization culture of normal spleen cells and MOPC 315 tumor cells. At the same time, the thymocytes from L-PAM treated MOPC-315 tumor bearers were unable to develop an antitumor cytotoxic response of their own when immunized in vitro in the absence of normal spleen cells. The possibility that the Lyt 2+ L3T4+ immunopotentiating cells in the spleens of L-PAM treated MOPC-315 tumor bearers represent immature cells that have been induced by the chemotherapy to migrate from the thymus into the spleen is discussed. PMID- 2891628 TI - Pathogenesis and treatment of polycystic ovary disease. PMID- 2891629 TI - Varicocele: medical and surgical treatment. AB - Varicocele is the most frequent finding in male infertility. Thirty percent of infertile male patients requesting treatment present with varicocele. Between December 1971 and December 1984, 151 infertile patients presenting varicocele were treated in this study: 28 underwent medical treatment, 38 surgical treatment, and 23 both medical and surgical treatment. The spermograms of all the patients were studied before and after treatment. The following variables were considered: volume, sperm count, percentages of general motility and of grade III sperm, and of oval forms. There was not a significant statistical difference in the analysis of the spermogram parameters before and after treatment in the three groups. The pregnancy rate for the medical-surgical group was 60.9% and for the surgical group 47.4%--not a statistically significant difference. The purely medically treated group had a pregnancy rate of 25%, which is significantly lower than the other groups. PMID- 2891631 TI - The importance of laparoscopic coagulation of mild endometriosis in infertile women. AB - To evaluate the effect of fulguration of endometriotic implants in patients with mild endometriosis, we divided 123 patients into two groups: (A) patients whose endometriotic implants were coagulated, and (B) patients whose implants were left intact. In group A, 42 of 69 (60.8%) patients achieved a pregnancy within eight cycles following laparoscopic fulguration, in comparison with 10 of 54 (18.5%) patients from group B. The difference between this study and others is that all other infertility factors were meticulously corrected prior to laparoscopic treatment, and patients were allowed at least eight "normal" cycles before their endometriosis was treated. This is a report of 8 months' postoperative follow-up. The study was prospective and treatment was assigned randomly. We feel that laparoscopic fulguration significantly improves fertility in these carefully selected patients. PMID- 2891630 TI - Postcoital test abnormalities in relation to contraceptive use. AB - Abnormalities of cervical mucus can have a bearing on a woman's fertility. One means of detecting the presence of such abnormalities is the postcoital test (PCT). As part of a population-based case control study of risk factors for infertility, the reproductive, contraceptive, medical, and sexual histories of women seeking treatment for infertility who had abnormal PCT results were compared with those of fertile controls. A greater proportion of infertile women with an abnormal PCT had previously used a diaphragm than had control women (relative risk (RR) = 3.5, 95% CI = 1.1-11.3). The excess risk associated with use of a diaphragm was particularly high for women who had used one for longer than one year (RR = 7.3, 95% CI = 1.4-37.8), or within one year of attempting to conceive (RR = 5.5, 95% CT = 1.4-22.1). No increased risk was associated with the use of other barrier methods, oral contraceptives, or the intrauterine device. PMID- 2891632 TI - Hysteroscopic evaluation and endocrinological aspects of women with mullerian anomalies and oligomenorrhea. AB - In a prospective study of 28 consecutive patients with oligomenorrhea, two had uterus didelphys, and the incidence of mild mullerian anomalies was 50.0%, assessed by hysterosalpingography (HSG). The objects of the study were (1) to confirm these mullerian anomalies hysteroscopically, (2) to assess the predictive value of an abnormal and a normal fundal contour on the HSG, and (3) to find anamnestic, chromosomal, or hormonal characteristics, if any, for women with oligomenorrhea and mullerian anomalies. Twelve patients underwent HSG followed by hysteroscopy, at which a septum or fundal convexity was confirmed in six out of seven patients in whom HSG had shown a mild to moderate indentation of the fundus, but showed no such sign in any of the five patients in the control group in whom the uterine contours had been normal on the HSG (P less than .01). There were no evident anamnestic, chromosomal, or hormonal characteristics for women having uterine developmental anomalies and oligomenorrhea, but there was a major or minor shift in certain androgenic metabolites in some of the patients in this group. It is concluded that HSG seems of great value in diagnosing uterine septa, but hysteroscopy afforded more precise information concerning the degree of fundal anomaly. Longitudinal, more standardized studies are needed for further elucidation of the etiology of the oligomenorrhea in these patients. PMID- 2891633 TI - Prevalence of Chlamydia trachomatis and the genital mycoplasmas in a nonmetropolitan population. AB - Results of cultures from patients with nonspecific urethritis (NSU) during a 4 year period were retrospectively analyzed. NSU cultures included chlamydiae and mycoplasmas. Seventy-five of 2,408 cultures run by the Missoula Community Hospital microbiology laboratory were positive for chlamydiae (3%). Seventy-five of 1,944 mycoplasma cultures were positive for Mycoplasma hominis (4%), 532 of 1,944 for Ureaplasma urealyticum (27%), and 305 of 1,944, for both (15%), for a total of 46% culture positive for any genital mycoplasma. Results of a prospective study of 40 NSU patients' cultures were tabulated separately. From these 40 patients, no chlamydiae were isolated, but the cultures were 15% positive for M. hominis, 42% positive for U. urealyticum, and 10% positive for both. These studies suggest that the prevalence of chlamydiae may vary with patient population and geographic area. In our population, the mycoplasmas appear to be over 15 times as common (3% vs. 46%). PMID- 2891634 TI - Lack of correlation of ultrasonographically determined ovarian size with age, ponderal index, and hormonal factors in 45 patients with polycystic ovarian disease. AB - An ultrasonographic study was performed on 45 patients with polycystic ovarian disease. These patients demonstrated hirsutism, menstrual disturbances, or infertility, as well as an increased LH/FSH ratio and/or evidence of hyperandrogenemia. Ovarian size was not correlated with age, Ponderal Index, serum testosterone, prolactin, androstenedione, dehydroepiandrosterone sulfate or LH/FSH ratio in the 45 subjects studied. PMID- 2891635 TI - Initial experiences with subcutaneous pulsatile human menopausal gonadotropin administration: successful induction of ovulation in patients with polycystic ovarian disease. AB - Human menopausal gonadotropin (hMG) was administered to 10 patients with polycystic ovarian disease (PCOD) who had failed to ovulate in response to clomiphene citrate. Five patients (group 1) were treated with intramuscular hMG injections daily, on an individually adjusted regimen. Five others (group 2) were stimulated with subcutaneous hMG in a pulsatile fashion by means of a portable infusion minipump. The pulse doses ranged between 3.5 and 7.7 IU FSH per pulse at a constant frequency of 90 minutes. Sixteen of 18 treatment cycles were ovulatory, 9 under intramuscular, and 7 under subcutaneous treatment. A total of two patients conceived with singleton pregnancies, one in each treatment group. Neither ovarian hyperstimulation nor complications of injections were noted. The amount of subcutaneous hMG required to achieve ovulation was significantly less (46.5%; P less than .001) than that needed with intramuscular administration. However, there were no differences in the duration of stimulation periods, the lengths of luteal phases, or serum E2 and gonadotropin levels between the groups. In conclusion, pulsatile subcutaneous hMG administration may be an alternative delivery mode for patients with PCOD. PMID- 2891636 TI - Cyclic fluctuations of vasoactive intestinal polypeptide measured radioimmunologically in various regions of the human fallopian tube. AB - Levels of the neuropeptide VIP were measured by radioimmunoassay in the isthmus, ampulla, and fimbriated end of the human fallopian tube during the follicular, ovulatory, and luteal phases as defined by plasma estradiol and progesterone concentrations. The regional concentration of VIP was in the order isthmus greater than ampulla greater than fimbriae. The VIP concentration increased by 170% from the follicular through the ovulatory to the luteal phase in the isthmus. Such a tendency was seen also in the ampulla when the peptide level was expressed in terms of the total regional content. In fact, when expressed as total content, VIP was highest in the ampulla at all cyclic stages. Since there are no major fluctuations in the water content of the tubal tissues in the three phases, the observed changes in VIP levels represent real fluctuations at the neural level in a manner similar to that previously shown for the neurotransmitter norepinephrine. PMID- 2891637 TI - Cryptorchidism: a morphological study of 670 biopsies. AB - Among a series of 512 boys with an empty scrotum, 495 (96.7%) were found to have cryptorchidism, 4 had ectopia and 13 unilateral anorchia. Cryptorchidism was bilateral in 106 boys (21.4%). The only anomaly consistently associated with cryptorchidism was a detached epididymis, present in 31 patients. A total of 670 biopsies were studied, 441 of which came from cryptorchid and 229 from scrotal testes. Spermatogonial counts, performed according to Mancini's method, showed the germ cell population to be diminished in nearly all cryptorchid testes. The seven boys who still had a well preserved germ cell population were found in a group of 51 patients operated before age three; four of the seven boys with normal counts were below age one. No difference in the mean spermatogonial counts was found between uni- und bilateral cryptorchidism and ectopia, with the exception of bilaterally intraabdominal testes whose spermatogonial cell loss was particularly severe. Mean counts remained constant during childhood, no gradual increase with age having been observed. The scrotal testes in unilateral cryptorchidism showed cell loss in 30.1% of the cases, the germ cell depletion being severe in one out of every six cases. In the remaining scrotal testes, the counts were in the low normal range with a significantly lower mean than that found in scrotal testes associated with anorchia. Control biopsies were performed several months or years after orchidopexy in 18 boys with unilateral and in 24 boys with bilateral cryptorchidism. Orchidopexy does not improve the number of germ cells in either originally cryptorchid or in scrotal testes, the only postoperative change being an increase in tubular diameter. A search for malignant tumours which could have developed in this series has remained negative. According to our data, no optimal time for orchidopexy can be proposed. The damage to germ cells, once established, seems to remain unchanged during childhood at least after age three, and does not warrant special timing for operative correction of cryptorchidism. PMID- 2891638 TI - MEN-2 syndrome: the value of screening and central registration; a study of six kindreds in The Netherlands. PMID- 2891639 TI - Characteristics of a family with the MEN-2A syndrome. PMID- 2891640 TI - Multiple endocrine neoplasia type 2A: a Northern Ireland and Australian family. PMID- 2891641 TI - Screening for early asymptomatic pheochromocytoma in MEN-2. PMID- 2891642 TI - Calcitonin gene-related peptide and calcitonin in MEN-2 and sporadic pheochromocytomas: an immunohistochemical study. PMID- 2891643 TI - Clinical value of calcitonin and carcinoembryonic antigen doubling times in medullary thyroid carcinoma. PMID- 2891644 TI - Subtotal adrenalectomy in multiple endocrine neoplasia type 2. PMID- 2891645 TI - Thyroid C-cell hyperplasia and micronodules in close relatives of MEN-2A patients: pitfalls in early diagnosis and reevaluation of criteria for surgery. PMID- 2891646 TI - Immunohistochemistry in medullary thyroid carcinoma: prognosis and distinction between hereditary and sporadic tumors. PMID- 2891647 TI - Plasma and tumor levels of somatostatin (SRIF) and somatostatin immunochemistry in medullary thyroid carcinoma: apparently discrepant preliminary results. PMID- 2891648 TI - Different mechanisms of calcitonin, calcitonin gene-related peptide, and somatostatin regulation by glucocorticoids in a cell culture of human medullary thyroid carcinoma. PMID- 2891650 TI - Application of minisatellite DNA probes to linkage in MEN-2. PMID- 2891649 TI - Studies of multiple endocrine neoplasia type 2A syndrome: linkage analyses and comparison of constitutional and tumor genotypes. PMID- 2891651 TI - One large kindred excludes a locus for multiple endocrine neoplasia type 2A from about 25% of the human autosomal genetic map. PMID- 2891653 TI - The Second International Workshop on Multiple Endocrine Neoplasia Type 2 Syndromes. Cambridge, England, September 17-20, 1986. Proceedings. PMID- 2891652 TI - Where is the locus for multiple endocrine neoplasia type 2A? PMID- 2891654 TI - Impact of prospective screening for multiple endocrine neoplasia type 2. PMID- 2891655 TI - Screening in medullary thyroid carcinoma. PMID- 2891656 TI - Ultracytochemical localizations of adenylate cyclase, guanylate cyclase and cyclic 3',5'-nucleotide phosphodiesterase activity on the trophoblast in the human placenta. Direct histochemical evidence. AB - Ultracytochemical localizations of cyclic nucleotide-metabolizing enzymes, namely adenylate cyclase (AC), guanylate cyclase (GC) and cyclic 3',5'-nucleotide phosphodiesterase (PDE), have been demonstrated in the human term placenta. AC activity was found positive on the basal plasma membrane of the syncytiotrophoblast and on the pinocytotic vesicle of the fetal capillary endothelial cell. GC activity was observed to be strong on the plasma membrane of the microvilli of the syncytiotrophoblast. The cAMP PDE activity was shown positive both on the basal plasma membrane and on the microvillous membrane, while cGMP PDE activity was exclusively confined to the microvilli of the syncytiotrophoblast. These observations suggest that the syncytiotrophoblast plays an important role in the cyclic nucleotide metabolism in the human term placenta and that there might be significant functional differences between its basal plasma membrane and its microvillous membrane. PMID- 2891658 TI - Protect our children. PMID- 2891657 TI - Alteration in hematopoietic stem cell seeding and proliferation by both high and low dose rate irradiation of bone marrow stromal cells in vitro. AB - The mechanism of physiologic alteration by high (HDR) or low dose rate (LDR) (5 or 120 cGy/min) irradiation of plateau-phase bone marrow stromal cell cultures was investigated using a technique of in vitro bone marrow transplantation. Purified stromal cell cultures from C57BL/6J, C3H/HeJ, or (C57BL/6J X DBA2/J)F1 (B6D2F1) mouse marrow were irradiated to doses of 2.5 to 10 Gy at LDR or 10-100 Gy at HDR and were then engrafted in vitro with nonadherent hematopoietic cells from murine continuous bone marrow cultures. Parameters of engraftment quantitated included: (1) numbers of adherent proliferating hematopoietic cell colonies, "cobblestone islands" (2) cumulative production of nonadherent hematopoietic cells over 8 weeks after engraftment, (3) M-CSF, GM-CSF and multi CSF (IL-3) dependent hematopoietic progenitor cells forming greater than or equal to 50 cell colonies in semisolid medium, (4) cumulative production of CFUs, and (5) number of adherent stromal cells positive for detectable extracellular laminin or collagen type IV (markers of endothelial cells, reticular adventitial cells, or sinus lining cells). There was a decrease in cobblestone island formation between 5 and 10 Gy and this parameter possibly increased at doses of 50 and 100 Gy. There was no difference between HDR and LDR irradiation to 10 Gy. Irradiation to doses above 10 Gy decreased support of engrafted cells forming CFU GM and CFU-GEMM. Measures of CFUs after 10 Gy were variable but indicated a possible increase with HDR and no effect of LDR at 1 week and a decrease in both HDR and LDR groups at 3 weeks after engraftment. Thus, LDR and HDR irradiation in vitro alter several specific parameters of marrow stromal cell support for engrafted hematopoietic stem cells. PMID- 2891660 TI - Evaluating capitation payments. PMID- 2891659 TI - The viewbox. Blastomycosis. PMID- 2891661 TI - Hold harmless agreements. Benefits and drawbacks. PMID- 2891663 TI - Colorectal carcinomas. PMID- 2891662 TI - Surgery for primary hyperparathyroidism. PMID- 2891664 TI - Recurrent gastrointestinal bleeding. PMID- 2891665 TI - Cancer of the trachea. PMID- 2891666 TI - Dr. Charles Chandler of Chandlerville. PMID- 2891667 TI - Adolescent sexuality. PMID- 2891668 TI - What is a Certified Medical Assistant? PMID- 2891669 TI - [International Confederation of Midwives, 21st Congress]. PMID- 2891670 TI - Induction of preleukemic stage of adult T cell leukemia-like disease in rabbits. AB - Two HTLV-I-carrying T cell lines were prepared from peripheral lymphocytes of a virus-infected (B/J X Chbb:HM) F1 rabbit, and these cells were inoculated intraperitoneally into 5 newborn F1 rabbits. These animals were killed 3-5 weeks later. Their leukocyte counts were higher than those in normal control animals, with abnormal lymphocytes amounting to 3-5% of total leukocytes. Histological examination showed leukemic infiltration in liver, spleen, lung and kidneys of all these animals. The peripheral lymphocytes at first lacked HTLV-I antigens, but became antigen-positive after in vitro culture. Southern blot analysis of these cells revealed HTLV-I integration patterns different from those of the inoculated cells. PMID- 2891671 TI - HTLV-I carrier mothers with high-titer antibody are at high risk as a source of infection. AB - High-titer antibody against HTLV-I in carrier mothers is proposed as a secondary parameter for risk of viral transmission to the children via milk. For titration of antibodies, a less expensive modified gelatin particle agglutination assay (approximately 40% of the standard cost) was developed. None of 11 carrier mothers with antibody titers of less than 4000 had carrier children, whereas 11 out of 17 mothers with titers of 256,000 or higher had carrier children. The antibody titer was correlated with antigen-bearing cells detectable in cultures of peripheral blood T-lymphocytes, which was previously described as a marker of risk for transferring HTLV-I to children. PMID- 2891672 TI - Decreased sensitivity to phalloidin of aged F344/DuCrj rat hepatocytes. AB - The phalloidin sensitivity of hepatocytes resulting in the formation of cytoplasmic blebs was examined with cells isolated from 73- to 74-week-old and 99 to 100-week-old F344/DuCrj rats of both sexes by a collagenase perfusion method. The cells isolated from aged rats were less sensitive to the toxin than those obtained from 10- to 14-week-old rats. The decrease in the sensitivity was more marked in males than in females, and it appeared at an earlier age in the former than in the latter. Phalloidin consumption experiments showed decreases in the cellular uptake of the toxin in aged rats, and these were more marked in males than in females. The low cellular uptake of the toxin seemed to play an important role in the low sensitivity of the cells in aged rats. Although histological and histochemical examinations showed the development of foci of altered hepatocytes in the aged rat liver, the foci were estimated to account for less than 1.5% of liver tissues. Thus, the decrease in the sensitivity of the cells isolated from whole liver tissues might mainly be attributed to the decrease in the sensitivity of otherwise normal-looking hepatocytes. PMID- 2891673 TI - Effect of the repartitioning agent cimaterol on growth, carcass and skeletal muscle characteristics in lambs. AB - Ten crossbred (Suffolk X Rambouillet) whether lambs were randomly assigned to receive 0 or 10 ppm cimaterol (CIM) in a completely mixed high-concentrate diet for 8 wk. Total weight gain and feed efficiency were improved 29% (P less than .05) and 14%, respectively, in the CIM-fed group. CIM also improved (P less than .01) dressing percent by 4.9 percentage points and improved yield grade by one grade. CIM increased longissimus muscle (LD) area 38% (P less than .01) and the yield of four lean cuts 28% (P less than .01). No difference was found in the proportion of type I (slow-contracting, oxidative) and type II (fast-contracting, mixed glycolytic/oxidative) fibers in LD and semitendinosus (ST) muscles between control and CIM groups, indicating no change in fiber type. The cross-sectional area of type II fibers in LD and ST muscles of the CIM group was 2,081 and 1,951 micron 2 as compared with 1,391 and 1,296 micron2 of the control group, respectively. The increase was approximately 50% (P less than .01). No difference was found in cross-sectional area of type I fibers, indicating that the increase of muscle mass was due to hypertrophy of type II fibers only. DNA concentration (micrograms/g wet muscle or microgram/g protein) of CIM muscle was much lower (P less than .01) than that of control muscle, suggesting that the protein accretion in muscle was accomplished without additional incorporation of nuclei from satellite cells. PMID- 2891674 TI - Cholinergic neuromodulation by prostaglandin D2 in canine airway smooth muscle. AB - To determine whether prostaglandin D2 (PGD2) modulates cholinergic neurotransmission in airway smooth muscle and, if so, what the mechanism of action is, we studied bronchial segments from dogs under isometric conditions in vitro. PGD2 (10(-8)-10(-5) M) elicited dose-dependent muscle contraction, which was reduced after blockade of muscarinic receptors, so that 50% effective dose (ED50) increased from 1.3 +/- 0.3 X 10(-6) to 3.9 +/- 1.0 X 10(-6) M by atropine (10(-6) M) (mean +/- SE, P less than 0.05). Physostigmine, at a concentration insufficient to alter base-line tension (10(-8) M), enhanced the PGD2-induced contraction and decreased ED50 to 6.4 +/- 0.5 X 10(-7) M (P less than 0.05). When added at the highest doses that did not cause spontaneous contraction (1.9 +/- 0.5 X 10(-7) M), PGD2 increased the contractile response to electrical field stimulation (1-50 Hz) by 21.9 +/- 6.6% (P less than 0.001). In contrast to this effect, the response to administered acetylcholine was not affected by PGD2. On the other hand, PGD2-induced augmentation of the response to electrical field stimulation (5 Hz) was further increased from 23.6 +/- 3.0 to 70.4 +/- 8.8% in the presence of physostigmine (10(-8) M) and was abolished by atropine but not affected by the alpha-adrenergic antagonist phentolamine or the histamine H1 blocker pyrilamine. These results suggest that the contraction of airway smooth muscle induced by PGD2 is in in part mediated by a cholinergic action and that PGD2 prejunctionally augments the parasympathetic contractile response, likely involving the accelerated release of acetylcholine at the neuromuscular junction. PMID- 2891676 TI - Characterization of glutamic acid uptake by bovine pulmonary arterial endothelial cells. AB - L-Glutamic acid uptake by bovine pulmonary arterial endothelial cells in culture increased linearly with time up to 30 min and did not show saturation with increased substrate concentration up to 6 X 10(-3) M. The uptake per cell decreased as cell density increased and was lowest when the cells became fully confluent. Most of the uptake was sodium dependent, although the relative contribution of sodium-independent uptake increased with an increase in cell density. Cysteic and aspartic acid strongly inhibited L-glutamic acid uptake, but at higher cell densities this effect was less pronounced than at low densities. Other amino acids, including leucine, glutamine, and serine, exerted a modest inhibitory effect at both high and low cell densities. Thus pulmonary arterial endothelial cells contain similar membrane transport systems for L-glutamic acid as those previously described for fibroblasts, hepatocytes, and nerve cells. However, quantitative properties of the transport systems differ depending on the state of cellular density in monolayers. PMID- 2891675 TI - Exercise training and the arterial baroreflex. AB - To test the hypothesis that endurance training would attenuate the carotid sinus baroreflex in rats, studies were undertaken with 25 nontrained (NT) and 22 trained (T) male Sprague-Dawley rats that were exercised for 11-14 wk. Maximal O2 consumption was significantly increased 10% after training. The left carotid sinus region was functionally isolated in anesthetized animals. Subsequently, static carotid sinus pressure was raised in 20-Torr increments from 95 Torr until a maximal response in systemic arterial pressure and regional blood flows was recorded. Compared with the NT group, baroreflex control of blood pressure and calculated regional resistance of the T animals was less responsive to changes in carotid sinus pressure. Resting blood pressure, heart rate, and changes in peripheral blood flow velocity were similar for the two groups. Peripheral sensitivity to phenylephrine-HCl and hexamethonium bromide were also similar in the T and NT groups. It was concluded that the arterial baroreflex control of blood pressure was attenuated by exercise training. These findings support the concept that the trained individual is at disadvantage during hypotensive episodes and that endurance training will attenuate the sympathetic component of the arterial baroreflex. PMID- 2891678 TI - Medium vessel vasculitis of cutaneous type. PMID- 2891677 TI - Effect of hyperoxia on glutathione levels and glutamic acid uptake in endothelial cells. AB - Intracellular glutathione was increased by 80% after exposure of bovine pulmonary arterial endothelial cells to 80% O2 (hyperoxia) for 24 h. No change in glutathione occurred in cells exposed to hypoxia (3% O2) for a corresponding period of time. The rate of uptake of [3H]glutamic acid also increased by 35-55% after 24 h of exposure of cells to hyperoxia, whereas exposure to hypoxia had no effect on the [3H]glutamic acid uptake. The increase in glutamic acid uptake reflected a specific effect on amino acid transport systems rather than a change in cell membrane permeability. The major portion of the increased uptake was inhibited by the elimination of sodium and the addition of the competitive inhibitor, cystine, to the incubation medium. Thus increases in glutamic acid uptake parallel increases in cellular glutathione, and glutamic acid may be a regulating factor in the increase in glutathione after exposure to hyperoxia. PMID- 2891679 TI - Temperature-sensitive Escherichia coli mutant with an altered initiation codon of the uncG gene for the H+-ATPase gamma subunit. AB - A mutant of Escherichia coli showing temperature-sensitive growth on succinate was isolated, and its mutation in the initiation codon (ATG to ATA) of the uncG gene (coding for the gamma subunit of H+-ATPase F0F1) was identified. This strain could grow on succinate as the sole carbon source at 25 and 30 degrees C, but not at 37 or 42 degrees C. When this strain was grown at 25 degrees C on succinate or glycerol, its membranes had about 15% of the ATPase activity of wild-type membranes, whereas when it was grown at 42 degrees C, its membranes had about 2% of the wild-type ATPase activity. Membranes of the mutant grown at 25 or 42 degrees C could bind F1 functionally, resulting in about 40% of the specific activity of wild-type membranes. The gamma subunit was identified in an EDTA extract of membranes of the mutant grown at 25 degrees C, but was barely detectable in the same amount of extract from the mutant grown at 42 degrees C. These results indicate that initiation of protein synthesis from the AUA codon is temperature sensitive and that the gamma subunit is essential for assembly of F1 in vivo as shown by in vitro reconstitution experiments (S. D. Dunn and M. Futai, J. Biol. Chem. 255:113-118, 1980). PMID- 2891680 TI - Molecular analysis and regulation of the glnA gene of the gram-positive anaerobe Clostridium acetobutylicum. AB - The nucleotide sequence of a 2.0-kilobase DNA segment containing the Clostridium acetobutylicum glnA gene was determined. The upstream region of the glnA gene contained two putative extended promoter consensus sequences (p1 and p2), characteristic of gram-positive bacteria. A third putative extended gram-positive promoter consensus sequence (p3), oriented towards the glnA gene, was detected downstream of the structural gene. The sequences containing the proposed promoter regions p1 and p2 or p3 were shown to have promoter activity by subcloning into promoter probe vectors. The complete amino acid sequence (444 residues) of the C. acetobutylicum glutamine synthetase (GS) was deduced, and comparisons were made with the reported amino acid sequences of GS from other organisms. To determine whether the putative promoter p3 and a downstream region with an extensive stretch of inverted repeat sequences were involved in regulation of C. acetobutylicum glnA gene expression by nitrogen in Escherichia coli, deletion plasmids were constructed lacking p3 and various downstream sequences. Deletion of the putative promoter p3 and downstream inverted repeat sequences affected the regulation of GS and reduced the levels of GS approximately fivefold under nitrogen-limiting conditions but did not affect the repression of GS levels in cells grown under nitrogen-excess conditions. PMID- 2891681 TI - Sequential regulation of developmental events during polar morphogenesis in Caulobacter crescentus: assembly of pili on swarmer cells requires cell separation. AB - Pili, along with the flagellum and DNA bacteriophage receptors, are structural markers for polar morphogenesis in Caulobacter crescentus. Pili act as primary receptors for a number of small, C. crescentus-specific DNA and RNA bacteriophages, and the timing of pilus-dependent adsorption of bacteriophage phiCb5 in synchronized cell populations has led to the general conclusion that pili are formed coordinately with the flagellum and other polar surface structures in the predivisional cell. The use of rotary platinum shadow casting and electron microscopy as a direct assay for formation of flagella and pili in synchronous cell cultures now shows, however, that when expressed as fractions of the swarmer cell cycle, flagella are assembled on the predivisional cells at approximately 0.8 and that pili are assembled on the new swarmer cells at approximately 0.1 of the next cell cycle. Adsorption of pilus-specific bacteriophage phiCb5 prevented the loss of pili from swarmer cells during development, which suggests that these structures are retracted at the time of stalk formation. Examination of temperature-sensitive cell division mutants showed that the assembly of pili depends on completion of cell separation. These results indicate that the stage-specific events required for polar morphogenesis in C. crescentus occur sequentially, rather than coordinately in the cell cycle, and that the timing of these events reflects the order of underlying cell cycle steps. PMID- 2891682 TI - Use of lac fusions to measure in vivo regulation of expression of Escherichia coli proton-translocating ATPase (unc) genes. AB - In-frame fusions to lacZ were constructed in two adjacent genes of the unc operon of Escherichia coli, uncA and uncG, which code for the alpha and gamma subunits of the proton-translocating ATPase. After each fusion was moved into the E. coli chromosome, measurement of beta-galactosidase activities from single-copy genes showed that uncA was expressed significantly better in vivo than was uncG, but the relative expression dependent on the chromosomal location of each fusion and the presence or absence of other unc genes. PMID- 2891683 TI - Treatment-resistant mania with primary hypothyroidism: a case of recovery after levothyroxine. AB - A manic-depressive woman was unresponsive to treatment with lithium and neuroleptics during a period of mania. Additional levothyroxine treatment of her primary hypothyroidism resulted in rapid and complete recovery from her mania. PMID- 2891684 TI - Long-term anxiolytic therapy: the issue of drug withdrawal. AB - Although widespread use has confirmed their efficacy as anxiolytic agents, the benzodiazepine drugs are indicated only for short-term or intermittent therapy at as low a therapeutic dose as possible because of their liability for causing dependence or abuse. When first introduced, benzodiazepine drugs appeared to be therapeutically equal or superior to barbiturate agents, while causing fewer side effects, being safer in overdose, and producing fewer dependence and abuse problems. Although benzodiazepine drugs have become the most commonly prescribed anxiolytic agents, evidence has emerged that their use in long-term therapy can cause severe withdrawal problems, even when relatively low doses are used or when the drug is discontinued gradually. Based on results from both animal models and clinical investigations, buspirone appears to be as effective in treating anxiety as the benzodiazepine drugs while causing fewer withdrawal problems. Data suggest no appreciable propensity to cause physical dependence or abuse associated with buspirone therapy. The drug demonstrates no cross-tolerance with either the barbiturate agents or the benzodiazepine drugs and seems to be a dysphoriant at high doses rather than a euphoriant. Although buspirone seems to be an appropriate drug for patients requiring longer-term anxiolytic therapy, careful monitoring for withdrawal problems and other adverse side effects is essential as buspirone is introduced to successive markets. PMID- 2891685 TI - Accident- and injury-related health-care utilization among benzodiazepine users and nonusers. AB - Benzodiazepine tranquilizers have been found to cause psychomotor and cognitive impairment, and there is evidence of an increased rate of automobile accidents among users of these drugs. To determine whether benzodiazepine users are more likely than nonusers to experience accidental injury requiring medical attention, we examined health-care utilization among 7,271 such users and an age- and sex matched sample of 65,439 nonusers, all of whom were enrolled in an "HMO-like" health insurance plan. Benzodiazepine users and nonusers were identified through a review of 4 months' prescription drug claims. Six months' health-care claims for each user and nonuser subsequent to the first observed claim for a benzodiazepine or nonbenzodiazepine agent, respectively, were compiled. Claims related to accidents were identified on the basis of physician-recorded diagnoses. Our results indicate that benzodiazepine users were significantly (p less than .01) more likely than nonusers to experience (1) at least one accident related episode of care; (2) a greater number of accident-related hospital admissions; and (3) a greater number of accident-related inpatient days. Accident related utilization was also significantly higher when users had recently filled a prescription for a benzodiazepine agent. Benzodiazepine users, however, also utilized significantly more non-accident-related health-care services than nonusers. The nature of the association between benzodiazepine use and a higher accident-related utilization is thus unclear. A pretest-posttest study is now being undertaken to ascertain the significance of these findings. PMID- 2891686 TI - Effects of minor tranquilizers and antidepressants on psychomotor performance. AB - Results of laboratory and epidemiologic studies have raised concern that psychotropic drugs may contribute to accidents. This article reviews studies of the effects of minor tranquilizer and antidepressant drugs on psychomotor performance. Data clearly demonstrate that the most commonly prescribed tranquilizer, diazepam, impairs many aspects of psychomotor performance for several hours after dosing, and there is no evidence that behavioral tolerance develops with continued drug use or that patients are differently affected than nonpatients. Lorazepam similarly impairs psychomotor performance. Other frequently prescribed benzodiazepine drugs have not been sufficiently examined to warrant conclusions about their psychomotor effects. A newly marketed nonbenzodiazepine anxiolytic, buspirone, has been shown to have few effects on performance skills. Only one antidepressant, amitriptyline, has been studied thoroughly enough to conclude that it impairs psychomotor performance. The few studies of other, newer antidepressants suggest they may cause less impairment; however, more research is needed to confirm this. PMID- 2891687 TI - Consent and liability: special problems with anxiolytics. AB - The use of benzodiazepine anxiolytic therapy has sometimes been associated with certain adverse reactions. The authors discuss the extent to which the clinician is responsible for warning patients that benzodiazepine therapy may result in addiction, withdrawal problems, and/or impaired cognitive and motor skills. The development of new anxiolytics such as buspirone, which seem to exert less effect on cognitive and motor skills and lack addiction potential (and thus withdrawal problems), presents the clinician with a treatment alternative. The authors review two legal cases involving benzodiazepine-induced driving impairment and discuss whether the clinician is obligated to prescribe the agent that generally demonstrates the least interference with such common activities as driving. Primary issues that arise in the discussion of physician responsibility are informed consent (both verbal and written) and the documentation of all treatment decisions. The authors recommend quality care and individualized treatment to avoid liability. PMID- 2891688 TI - Antianxiety therapy: potential value of long-term treatment. AB - Although short-term therapy for patients with anxiety disorders has been the accepted mode of therapy, it has become increasingly evident that certain patients with generalized anxiety disorder, panic disorder, and chronic illness may require longer-term therapy. Therapeutic goals for such patients include reducing anxiety symptoms, returning the patient to normal or near-normal functioning, and improving quality of life. Clinicians must choose the appropriate drug regimen with regard to duration, continuous versus intermittent treatment, and administration on a daily versus as-needed basis. Because of the nature of some anxiety disorders, intermittent therapy very often may be preferred. Benzodiazepines are highly effective and safe anxiolytics, but with continuous use these agents have demonstrated psychologic and physical dependence problems. Other agents, such as tricyclic antidepressants and monoamine oxidase inhibitors, also relieve anxiety, although they have been shown to be unsuited for indiscriminate use. Buspirone, a newer anxiolytic, seems to be both effective and without abuse or dependence potential. In all cases, the prudent clinician should combine good patient management within the context of a good doctor patient relationship. PMID- 2891689 TI - Serial plasma prolactin levels in neuroleptic-induced galactorrhea: a case report. AB - A patient was successfully treated with bromocriptine for neuroleptic-induced galactorrhea. The correlations of the weekly plasma prolactin levels with the severity of galactorrhea (p less than .005) and with the duration of treatment (p less than .001) were highly significant. Because symptomatic relief occurs an average of 6 to 8 weeks after initiation of pharmacotherapy, clinicians presently manage neuroleptic-induced galactorrhea by trial and error. The authors suggest that weekly plasma prolactin levels may provide a readily obtainable, early indicator of proper dosage and thus minimize the chance of iatrogenic illness. PMID- 2891690 TI - "Noncomplainers" or "noncompliers". PMID- 2891691 TI - Injection site leakage of neuroleptics. PMID- 2891693 TI - The properties of hybrid F1-ATPase enzymes suggest that a cyclical catalytic mechanism involving three catalytic sites occurs. AB - Maximal rates of ATP hydrolysis catalyzed by F1-ATPase enzymes are known to involve strong positive catalytic site cooperativity. There are three potential catalytic nucleotide-binding sites on F1. Two important and unanswered questions are (i) whether all three potential catalytic sites must interact cooperatively to yield maximal rates of ATP hydrolysis and (ii) whether a cyclical three-site mechanism operates as suggested by several authors. We have studied these two questions here by measuring the ATPase activities of hybrid enzymes containing normal beta-, gamma-, delta-, and epsilon-subunits together with different combinations of mutant and normal alpha-subunits. The mutant alpha-subunits were derived from uncA401, uncA447, and uncA453 mutant E. coli F1-ATPase, in which positive cooperativity between catalytic sites is strongly attenuated by defined mis-sense mutations. Our data show that three normal catalytic sites are required to interact in order to achieve maximal ATPase rates and suggest that a cyclical mechanism does operate. Hybrid enzyme containing one-third mutant alpha-subunit and two-thirds normal alpha-subunits had substantial but submaximal activity, showing that cooperativity between three sites in a noncyclical fashion, or between pairs of sites, can achieve effective catalysis. PMID- 2891692 TI - Isolation and sequence of the promoter region of the human multidrug-resistance (P-glycoprotein) gene. AB - Intrinsic and acquired multidrug resistance is an important problem in cancer therapy. Multidrug resistance results from overexpression of the MDR 1 gene, which encodes a drug-efflux pump called P-glycoprotein. We have isolated a 1 kilobase genomic fragment containing the major transcription initiation sites for the human MDR 1 gene. Ribonuclease protection experiments using this fragment indicate that normal human adrenal, colon, and liver cells, the human hepatoma cell line HepG2, and vinblastine-selected human KB multidrug-resistant cells initiate transcription of the MDR 1 gene at the same site within this fragment. The 0.43-kilobase region upstream from the major transcription initiation site linked to the chloramphenicol acetyltransferase gene showed promoter activity in CV-1 monkey kidney cells and in human KB cells. The putative promoter region has a consensus CAAT box and two GC box-like sequences, but no TATA sequence. This identification and isolation of promoter sequences for the MDR 1 gene will permit studies on how expression of this gene is regulated in normal human tissues and cancers. PMID- 2891694 TI - Mutation of a conserved glycine residue modifies the vanadate sensitivity of the plasma membrane H+-ATPase from Schizosaccharomyces pombe. AB - The structural gene pma+1 for the H+-ATPase from the fission yeast Schizosaccharomyces pombe has been isolated and sequenced. The intron-less gene encodes for a protein of Mr = 99,769 which is 75% homologous to those of Saccharomyces cerevisiae and Neurospora crassa. The S. pombe pma+1 gene complements not only S. pombe pma-1-1 but also S. cerevisiae pma-1-4 mutants selected for in vitro vanadate-resistant ATPase activity. The sequence of the S. pombe mutant pma-1-1 allele reveals that the glycine residue 268, which is perfectly conserved in the transduction domain of all animal and fungal transport ATPases sequenced so far, is modified into an aspartate residue by the mutation. Replacement of glycine 268 by aspartate has been monitored by the appearance of a new PvuI restriction site in the mutant DNA. Mitotic cosegregation has been observed between the PvuI site and vanadate-resistant ATPase activity in a growing population of S. pombe transformants. PMID- 2891695 TI - Characterization of the cyclic AMP-independent actions of somatostatin in GH cells. I. An increase in potassium conductance is responsible for both the hyperpolarization and the decrease in intracellular free calcium produced by somatostatin. AB - The neuropeptide somatostatin causes membrane hyperpolarization and reduces the intracellular free calcium ion concentration ([Ca2+]i) in GH pituitary cells. In this study, we have used the fluorescent dyes bisoxonol (bis,-(1,3 diethylthiobarbiturate)-trimethineoxonol) and quin2 to elucidate the mechanisms by which these ionic effects are triggered. Addition of 100 nM somatostatin to GH4C1 cells caused a 3.4 mV hyperpolarization and a 26% decrease in [Ca2+]i within 30 s. These effects were not accompanied by changes in intracellular cAMP concentrations and occurred in cells containing either basal or maximally elevated cAMP levels. To determine which of the major permeant ions were involved in these actions of somatostatin, we examined its ability to elicit changes in the membrane potential and the [Ca2+]i when the transmembrane concentration gradients for Na+, Cl-, Ca2+, and K+ were individually altered. Substitution of impermeant organic ions for Na+ or Cl- did not block either the hyperpolarization or the decrease in [Ca2+]i induced by somatostatin. Decreasing extracellular Ca2+ from 1 mM to 250 nM abolished the reduction in [Ca2+]i but did not prevent the hyperpolarization response. These results show that hyperpolarization was not primarily due to changes in the conductances of Na+, Cl-, or Ca2+. Although the somatostatin-induced decrease in [Ca2+]i did require Ca2+ influx, it was independent of changes in Na+ or Cl- conductance. In contrast, elevating the extracellular [K+] from 4.6 to 50 mM completely blocked both the somatostatin induced hyperpolarization and the reduction in [Ca2+]i. Furthermore, hyperpolarization of the cells with gramicidin mimicked the effect of somatostatin to decrease the [Ca2+]i and prevented any additional effect by the hormone. These results indicate that somatostatin increases a K+ conductance, which hyperpolarizes GH4C1 cells, and thereby secondarily decreases Ca2+ influx. Since the somatostatin-induced decrease in [Ca2+]i is independent of changes in intracellular cAMP levels, it may be responsible for somatostatin inhibition of hormone secretion by its cAMP-independent mechanism. PMID- 2891696 TI - Characterization of the cyclic AMP-independent actions of somatostatin in GH cells. II. An increase in potassium conductance initiates somatostatin-induced inhibition of prolactin secretion. AB - The neuropeptide somatostatin inhibits prolactin release from GH4C1 pituitary cells via two mechanisms, inhibition of stimulated adenylate cyclase activity and an undefined cAMP-independent process. Somatostatin also hyperpolarizes GH4C1 cells and reduces their intracellular free Ca2+ concentration ([Ca2+]i) in a cAMP independent manner. To determine whether these ionic changes were involved in the cAMP-independent mechanism by which somatostatin inhibited secretion, changes in cAMP levels were prevented from having any biological consequences by performing experiments in the presence of a maximal concentration of a cAMP analog. Under these conditions, inhibition of prolactin release by somatostatin required a transmembrane concentration gradient for K+ but not one for either Na+ or Cl-. However, elimination of the outward K+ gradient did not prevent somatostatin inhibition of vasoactive intestinal peptide-stimulated hormone release. Therefore, somatostatin's cAMP-mediated mechanism does not require a K+ gradient, whereas its cAMP-independent inhibition of secretion appears to result from a change in K+ conductance. Consistent with this conclusion, membrane hyperpolarization with gramicidin (1 microgram/ml) mimicked somatostatin inhibition of prolactin release. In addition, the K+ channel blocker tetrabutylammonium prevented the effects of somatostatin on the membrane potential, the [Ca2+]i and hormone secretion. Nonetheless, a K+ gradient was not sufficient for somatostatin action. Even in the presence of a normal K+ gradient, somatostatin was only able to inhibit prolactin release when the extracellular Ca2+ concentration was at least twice the [Ca2+]i. Furthermore, the calcium channel blocker, nifedipine (10 microM), which prevents the action of somatostatin to reduce the [Ca2+]i, specifically blocked inhibition of prolactin release via somatostatin's cAMP-independent mechanisms. Therefore, a decrease in Ca2+ influx through voltage-dependent Ca2+ channels produces both the fall in [Ca2+]i and inhibition of hormone secretion in response to somatostatin. PMID- 2891697 TI - Rearrangement of both alleles of human chromosome 8 in HeLa cells, one of them as a result of papillomavirus DNA integration. AB - Integration of papillomavirus in the genome of the host cell has been found associated with malignant cases of cervical carcinoma. To determine what role viral integration plays as part of the pathogenic mechanism resulting in a cancer cell, the structure of integrated papillomavirus DNA (human papillomavirus DNA 18) segments and its cellular flanking sequences in HeLa cells as well as the corresponding normal human allele have been characterized. All integrated viral DNA segments have the same human DNA sequences in their 5' flank. The use of human sequence flanking the viral DNA as a probe detected the presence of four different forms of this human DNA region based on restriction fragment length polymorphism. Three of these forms can be linked to integrated viral DNA from human papillomavirus 18. The remaining form could not be linked to viral DNA and did not have a germline pattern in its 5'-end suggesting that it was also structurally altered. None of the forms of the human sequence present in HeLa cells has the complete structure of the germline normal allele characterized in DNA from placenta and human fibroblasts IMR-90. This observation suggests that HeLa cells carry a structural alteration in both alleles of the same locus, one of which was caused by integration of papillomavirus DNA. This locus is located on a chromosome fragile site. These rearrangements will result in a homozygous situation which is interpreted as affecting a recessive phenotype which might be involved in some aspect of tumorigenesis. PMID- 2891698 TI - Characterization and function of catalytic subunit alpha of H+-translocating adenosine triphosphatase from vacuolar membranes of Saccharomyces cerevisiae. A study with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole. AB - Subunit alpha (Mr 89,000) from vacuolar membrane H+-translocating adenosine triphosphatase of the yeast Saccharomyces cerevisiae was found to bind 8 azido[alpha-32P]adenosine triphosphate. Labeling by this photosensitive ATP derivative was saturable with an apparent dissociation constant of 10(-6) to 10( 5) M and decreased in the presence of ATP and ADP. The enzyme was inactivated by 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl), with about 1 microM causing half-maximal inactivation in the neutral pH range. This inactivation was prevented by the presence of ATP, ADP, or adenosyl-5'-yl imidodiphosphate (AMP PNP). The original activity was restored by treating the inactivated enzyme with 2-mercaptoethanol. Kinetic and chemical studies of the inactivation showed that the activity was lost on chemical modification of a single tyrosine residue per molecule of the enzyme. When the enzyme was inactivated with [14C]NBD-Cl, subunit alpha was specifically labeled, and this labeling was completely prevented by the presence of ATP, GTP, ADP, or AMP-PNP. From these results, it was concluded that subunit alpha of yeast vacuolar H+-ATPase has a catalytic site that contains a single, essential tyrosine residue. The kinetics of single site hydrolysis of [gamma-32P]ATP (Grubmeyer, C., Cross, R. L., and Penefsky, H. S. (1982) J. Biol. Chem. 257, 12092-12100) indicated the formation of an enzyme-ATP complex and subsequent hydrolysis of bound ATP to ADP and Pi at the NBD-Cl-sensitive catalytic site. NBD-Cl inactivated the single site hydrolysis and inhibited the formation of an enzyme-ATP complex. Dicyclohexylcarbodiimide did not affect the single site hydrolysis, but inhibited the enzyme activity under steady-state conditions. PMID- 2891699 TI - Structure and expression of the rat transthyretin (prealbumin) gene. AB - The rat transthyretin gene, 7.3 kilobase pairs (kb) long, with 14.5 kb of 5' flanking and 12.2 kb of 3' flanking region was cloned and characterized. The gene contained four exons. A "TATA box" sequence (5'-TATATAA-3') and a "CAAT box" sequence (5'-GTCAAT-3') were located 23 and 95 nucleotides upstream, respectively, from the major transcription start site. Nucleotides -51 to -189 were highly conserved (93% homology between rats and humans, 97% homology between rats and mice). Tandem repeats of sequences of 5'-AC-3' and 5'-ACACATGC-3' in the 5' flanking region, of 5'-GAAA-3' in the first intron, and of 5'-GT-3' in the third intron of the gene were observed. Using specific cDNA probes, tissue specificity and regulation of transthyretin mRNA biosynthesis during embryogenesis were analyzed. Transthyretin expression occurred first in the yolk sac, then decreased when expression increased in fetal liver. Presumptive choroid plexus cells in the inner lining of the neural tube expressed transthyretin early in gestation (11 days before birth) with a maximum immediately preceding the spurt of brain growth around birth. Partial hepatectomy of adult rats induced both an acute phase response and regenerative growth in liver. The decrease in transcription of the transthyretin gene in liver, which is characteristic for the acute phase response, was overridden by stimulation of gene expression after partial hepatectomy. This stimulation also affected transthyretin expression in choroid plexus. PMID- 2891700 TI - Protons in the thylakoid membrane-sequestered domains can directly pass through the coupling factor during ATP synthesis in flashing light. AB - Thylakoid membranes contain sequestered domains in which protons are held in a metastable state out of equilibrium with those in the inner (lumen) or the outer aqueous bulk phases unless the membranes are made leaky by, for instance, the addition of uncouplers. Previously, it has not been clear whether such sequestered domain protons are: 1) directly on a localized pathway into the CF0 CF1; 2) on an ultimately delocalized pathway comprising domains----lumen----CF0 CF1; or 3) perhaps not importantly involved in any way with proton gradient linked ATP formation. Recent developments now permit a test of the above possibilities. The test for the possible mode of involvement of domain protons in energy coupling utilized single turnover flashes to energize electric field driven ATP formation, as influenced by both the proton depletion level of the sequestered domains and whether the thylakoids were prepared in a way to show either a localized or delocalized proton gradient response in ATP formation (this response is reversibly controlled by incubation in low (localized coupling mode) or high KCl (delocalized mode) incubations (Beard, W. A., and Dilley, R. A. (1986) FEBS Lett. 201, 57-62; Chiang, G. and Dilley, R. A. (1987) Biochemistry 26, 4911-1916). Using thylakoids showing delocalized coupling responses, there was no influence of the reversible depletion of the sequestered domain buffering pool on the delta psi-driven ATP formation onset lag. Lumenal protons rather than domain protons in that case appear to be the first to be driven through the CF0 CF1 complex by the delta psi field. However, using thylakoids prepared to be in the localized gradient coupling mode, protons in the domains, rather than those in the lumen, are the first to pass through the CF0-CF1 complex in the onset of energization. We conclude that the sequestered domain protons, in the latter case only, are obligatorily in the main proton diffusion pathway for energization of ATP formation and are the first protons (rather than lumen protons) driven through the CF1-CF0 complex by a delta psi field. PMID- 2891701 TI - Aspartate transcarbamylase from Leishmania donovani. A discrete, nonregulatory enzyme as a potential chemotherapeutic site. AB - Leishmania donovani is a protozoal pathogen that belongs to the kinetoplastida order. Unlike in other eucaryotic systems, the first three enzymes of the de novo pyrimidine biosynthetic pathway are not components of a multifunctional protein system. The three enzyme activities in the crude extract were separated on a Sephacryl S-200 column. Aspartate carbamoyltransferase (EC 2.1.3.2) has been purified to apparent homogeneity. The enzyme has an approximate molecular weight of 135,000 and seems to be a tetramer of equivalent subunits of molecular weight 35,000. The enzyme shows strictly hyperbolic kinetics with both the substrates under a variety of conditions and is not inhibited by nucleotide phosphates. Km for carbamyl phosphate is 3.1 x 10(-4) M and for aspartate is 7.6 x 10(-3) M. Apparently, the enzyme has no regulatory role in pyrimidine biosynthesis. N (Phosphonoacetyl)-L-aspartic acid is a powerful competitive inhibitor (Ki = 5 x 10(-7) M) for this enzyme with carbamyl phosphate as substrate. This inhibitor completely inhibits the growth of the vector form of organism at 60 microM and significantly affects the growth of the pathogenic form in a macrophage assay system. The potency of the inhibitor is comparable with allopurinol which is undergoing human clinical trial as an antileishmanial drug. PMID- 2891702 TI - Somatostatin pretreatment increases the number of somatostatin receptors in GH4C1 pituitary cells and does not reduce cellular responsiveness to somatostatin. AB - The GH4C1 pituitary cell line contains specific plasma membrane receptors for the inhibitory neuropeptide somatostatin (SRIF). Unlike other peptides which bind to cell surface receptors on these cells, SRIF is not rapidly internalized via receptor-mediated endocytosis. Here we examined the effects of chronic SRIF pretreatment on the subsequent ability of GH4C1 cells to bind and respond to this hormone. Treatment of cells with 100 nM SRIF increased [125I-Tyr1]SRIF binding to a maximum value of 220% of control after 20 h. Scatchard analysis demonstrated that the number, but not the affinity, of the receptors was altered. The effect of SRIF was dose-dependent (ED50 = 2.3 +/- 0.4 nM), was not mimicked by an inactive analog, and was specific for the SRIF receptor. Furthermore, pretreatment of cells with other agents, which mimic SRIF's action to decrease intracellular cAMP and free Ca2+ concentrations, did not mimic the SRIF-induced increase in receptor number. Thus, occupancy of the SRIF receptor was required for SRIF receptor up-regulation. Inhibition of protein synthesis with cycloheximide did not prevent the SRIF-induced increase in receptors, consistent with an effect of SRIF to either reduce receptor degradation or cause slow redistribution of preexisting receptors to the plasma membrane. In contrast to the effects on receptor binding, pretreating cells with SRIF did not alter either basal cAMP levels or the potency of SRIF to inhibit cAMP accumulation (ED50 = 0.5 +/- 0.2 nM). However, the maximum cAMP produced by stimulators of adenylyl cyclase was increased. The observation that chronic SRIF exposure did not cause homologous desensitization in GH4C1 cells and increased rather than decreased SRIF receptor number is consistent with the fact that this neuropeptide is not rapidly internalized by receptor-mediated endocytosis. PMID- 2891703 TI - Peptides derived from cleavage of prosomatostatin at carboxyl- and amino-terminal segments. Characterization of tissue and secreted forms in the rat. AB - Tissue and secreted forms of rat prosomatostatin and its cleavage products were characterized immunochemically using high performance liquid chromatography and sequence-specific radioimmunoassays directed against somatostatin-14 (S-14), S-28 (1-12), and S-28-(1-14). Acetic or hydrochloric acid extracts of hypothalamus, pancreas, stomach, and jejunum contained seven molecular forms of Mr = 10,400 (corresponding to prosomatostatin (pro-S], Mr = 6,800 (7-kDa peptide, consisting of an NH2-terminally truncated form of pro-S), Mr = 7,600 (8-kDa peptide, corresponding to pro-S-(1-76), i.e. pro-S minus the COOH-terminal -Arg-Lys-S-14), Mr = 5,600 (5-kDa peptide, corresponding to pro-S-(33-76)) and three peptides co chromatographing with synthetic S-14, S-28, and S-28-(1-12). Acid/ethanol extracts of these tissues contained pro-S, 8-kDa peptide, S-28, S-14, and S-28-(1 12) forms, but not the 7- and 5-kDa species. Pepstatin inhibited 7- and 5-kDa peptide formation in acetic acid extracts of tissues. The secreted forms consisted of the same five forms present in acid/ethanol or acetic acid plus pepstatin tissue extracts. The 7- and 5-kDa peptides were not secreted and appeared to be derived artifactually, presumably through the action of renin- and cathepsin D-like acid proteases. Accurate quantitation of the 8-kDa peptide by acid/ethanol extraction revealed a variable tissue distribution. Since the presence of the 8-kDa form provides evidence for direct processing of pro-S----S 14 + 8-kDa peptide, the present data suggest that pro-S----S-14 conversion is important for S-14 synthesis in the hypothalamus and pancreas, tissues rich in the 8-kDa form, but not in the stomach and jejunal mucosa, which contain low concentrations of this peptide. PMID- 2891704 TI - Mitochondrial ATP synthase. Interaction of a synthetic 50-amino acid, beta subunit peptide with ATP. AB - A 50-amino acid peptide predicted by chemical modification studies of F1 and by comparison with adenylate kinase to comprise part of an ATP-binding domain within the beta-subunit of mitochondrial ATP synthase has been synthesized and purified. In the numbering system used for bovine heart beta, the peptide consists of amino acid residues from aspartate 141 at the N-terminal end to threonine 190 at the carboxyl end. In Tris-Cl buffer, pH 7.4, the peptide undergoes a dramatic reaction with ATP resulting in precipitate formation. Analysis of the precipitate shows it to contain both peptide and ATP. Similar to the ATPase activity of F1 and the binding of nucleotide to the enzyme, the capacity of ATP to induce precipitation of the peptide is decreased markedly by lowering pH. Interaction of the peptide with the fluorescent ATP analog, TNP-ATP (2'(3')-O-(2,4-6 trinitrophenyl)-adenosine 5'-triphosphate), can be demonstrated in solution at low concentrations. A 7-fold enhancement in fluorescence is observed when 2.5 microM TNP-ATP interacts with 2.5 microM peptide. Divalent cation is neither required for ATP-induced precipitation of the peptide nor for demonstrating interaction between TNP-ATP and peptide, just as Mg2+ is not required for nucleotide binding to F1. These results indicate that the beta-subunit peptide studied here comprises at least part of a nucleotide-binding domain within the mitochondrial ATP synthase complex. PMID- 2891705 TI - Sequence of peptides from Saccharomyces cerevisiae glutamine synthetase. N terminal peptide and ATP-binding domain. AB - Sequences of seven tryptic peptides derived from Saccharomyces cerevisiae glutamine synthetase have been determined. The amino terminus of yeast enzyme is acetylated and has the following sequence: acetyl-Ala-Glu-Ala-Ser-Ile-Glu-Lys. Neither higher eukaryotic nor bacterial glutamine synthetase contain sequences homologous to this yeast amino terminus. 8-Azidoadenosine 5'-triphosphate [( alpha-32P]8-N3ATP) has been used to photolabel the ATP-binding site in yeast glutamine synthetase. Only one 32P-labeled tryptic peptide was obtained as a major fraction and its sequence is Glu-Gly-Tyr-Gly-X-Phe-Glu-Asp-Arg. Similar photolabeling experiments with bovine glutamine synthetase yielded a tryptic peptide whose sequence is Gly-X-Phe-Glu-Asp-Arg, where X is likely Tyr covalently attached by nitrene derived from [alpha-32P]8-N3ADP. Sequences very homologous to this nucleotide-binding site can be found in other eukaryotic enzymes but not in prokaryotic enzymes. In addition, the sequences of two cysteine-containing peptides and three other tryptic peptides were established. Sequences homologous to all these five peptides can be found in mammalian and plant enzymes. The homology between yeast and higher eukaryotic glutamine synthetases was sufficiently strong to suggest that the overall tertiary and quaternary structures of these enzymes must be similar. The sequences presented here, particularly the amino terminus sequence will be valuable in identifying the structural gene of yeast glutamine synthetase, thereby making it possible to study its transcriptional regulation. In addition, the sequences of the cysteine containing peptides will be useful in determining whether or not the covalent modification of a sulfhydryl group(s) is responsible for the modulation of glutamine synthetase activity. PMID- 2891706 TI - Prostaglandin E receptor enhancement of catecholamine release may be mediated by phosphoinositide metabolism in bovine adrenal chromaffin cells. AB - In the presence of ouabain, prostaglandin (PG) E2 stimulated a gradual secretion of catecholamines from cultured bovine adrenal chromaffin cells. PGE2 or ouabain alone evoked a marginal secretory response. The synergism of ouabain was also observed with muscarine. PGE2, like muscarine, induced a concentration-dependent formation of inositol phosphates: rapid rises in inositol trisphosphate and inositol bisphosphate followed by a slower accumulation of inositol monophosphate. This effect on phosphoinositide metabolism was accompanied by an increase in cytosolic free Ca2+. The potency of PGs (PGE2 greater than PGF2 alpha greater than PGD2) to stimulate catecholamine release was well correlated with that to affect phosphoinositide metabolism and that to increase the level of intracellular Ca2+. PGE2 did not stimulate cAMP generation significantly in bovine chromaffin cells. The effect of PGE2 on catecholamine release was mimicked by 12-O-tetradecanoylphorbol 13-acetate and A23187, but not by the cAMP analogue dibutyryl cAMP nor by forskolin. These results indicate that PGE2 may enhance catecholamine release from chromaffin cells by activating protein kinase C in concert with the increment of intracellular Ca2+. PMID- 2891707 TI - Molecular cloning and sequencing of a cDNA encoding the thioesterase domain of the rat fatty acid synthetase. AB - A cloned cDNA containing the entire coding sequence for the long-chain S-acyl fatty acid synthetase thioester hydrolase (thioesterase I) component as well as the 3'-noncoding region of the fatty acid synthetase has been isolated using an expression vector and domain-specific antibodies. The coding region was assigned to the thioesterase I domain by identification of sequences coding for characterized peptide fragments, amino-terminal analysis of the isolated thioesterase I domain and the presence of the serine esterase active-site sequence motif. The thioesterase I domain is 306 amino acids long with a calculated molecular mass of 33,476 daltons; its DNA is flanked at the 5'-end by a region coding for the acyl carrier protein domain and at the 3'-end by a 1,537 base pairs-long noncoding sequence with a poly(A) tail. The thioesterase I domain exhibits a low, albeit discernible, homology with the discrete medium-chain S acyl fatty acid synthetase thioester hydrolases (thioesterase II) from rat mammary gland and duck uropygial gland, suggesting a distant but common evolutionary ancestry for these proteins. PMID- 2891708 TI - N,N'-dicyclohexylcarbodiimide-binding proteolipid of the vacuolar H+-ATPase from oat roots. AB - The inhibitor N,N'-dicyclohexylcarbodiimide (DCCD) was used to probe the structure and function of the vacuolar H+-translocating ATPase from oat roots (Avena sativa var. Lang). The second-order rate constant for DCCD inhibition was inversely related to the concentration of membrane, indicating that DCCD reached the inhibitory site by concentrating in the hydrophobic environment. [14C]DCCD preferentially labeled a 16-kDa polypeptide of tonoplast vesicles, and the amount of [14C]DCCD bound to the 16-kDa peptide was directly proportional to inhibition of ATPase activity. A 16-kDa polypeptide had previously been shown to be part of the purified tonoplast ATPase. As predicted from the observed noncooperative inhibition, binding studies showed that 1 mol of DCCD was bound per mol of ATPase when the enzyme was completely inactivated. The DCCD-binding 16-kDa polypeptide was purified 12-fold by chloroform/methanol extraction. This protein was thus classified as a proteolipid, and its identity as part of the ATPase was confirmed by positive reaction with the antibody to the purified ATPase on immunoblots. From the purification studies, we estimated that the 16-kDa subunit was present in multiple (4-8) copies/holoenzyme. The purification of the proteolipid is a first step towards testing its proposed role in H+ translocation. PMID- 2891709 TI - The phenotype of five classes of T lymphoma mutants. Defective glycophospholipid anchoring, rapid degradation, and secretion of Thy-1 glycoprotein. AB - Thy-1 glycoprotein is a member of a class of proteins which are anchored to the plasma membrane via a covalently bound glycophospholipid. The biosynthesis and anchoring of Thy-1 were investigated in a family of wild-type and mutant (complementation groups A, B, C, E, and F) T lymphomas. The mutants all synthesize Thy-1 but fail to express it on the cell surface. Analysis of the size of D-[2-3H]mannose-labeled dolichol-linked oligosaccharides showed that the class E mutant is the only cell line which does not synthesize dolichol-P-P Glc3Man9GlcNAc2. Turnover and possible secretion of Thy-1 by mutant T lymphoma cells were documented in D-[2-3H]mannose pulse-chase experiments. The turnover of [3H]Thy-1 for all wild-type cells is considerably slower than for the mutant cells. Class B and E cells release appreciably more [3H]Thy-1 than wild-type cells. Additional experiments were performed to determine the electrophoretic mobility and hydrophobicity of cell-associated and released forms of Thy-1 labeled overnight with [3H]mannose. All wild-type and class A, C, E, and F mutant cells contain a major Triton X-114 binding species of cell-associated [3H]Thy-1. All extracellular [3H]Thy-1 was almost exclusively hydrophilic. The presence of two Thy-1 anchor components, ethanolamine and palmitate, was investigated. Biosynthetic labeling with [3H]palmitic acid showed that all of the wild-type cells but none of the mutants incorporated this anchor precursor into Thy-1. In [3H]ethanolamine-labeling experiments, incorporation was detected in the Thy-1 of all wild-type cells and in two mutants, S1A-b and T1M1-c. Based on the above studies, the phenotype of Thy-1 negative T lymphoma mutants can be re-evaluated. In classes A and F, dolichol-linked oligosaccharides appear normal and no anchor is detected. In class B, dolichol-linked oligosaccharides appear normal, a partial anchor may be present, and a substantial amount of Thy-1 is released. In class C, dolichol-linked oligosaccharides appear normal and a partial anchor may be present. In class E, truncated dolichol-linked oligosaccharides are formed, no anchor is detected, but a substantial amount of newly synthesized Thy-1 is released. These observations are discussed with reference to the possibility that the lesions which characterize the mutants pertain to the biosynthesis of the glycophospholipid moiety of Thy-1. PMID- 2891711 TI - Purification of the 170- to 180-kilodalton membrane glycoprotein associated with multidrug resistance. 170- to 180-kilodalton membrane glycoprotein is an ATPase. AB - 170-180-kDa membrane glycoprotein (P-glycoprotein) associated with multidrug resistance is involved in drug transport mechanisms across the plasma membrane of resistant cells. From sequence analysis of cDNAs of the P-glycoprotein gene, it is postulated that the active drug-efflux pump function may be attributable to the protein. However, purification of the P-glycoprotein while preserving its enzymatic activity has not been reported. In this study, we have purified the P glycoprotein from the human myelogenous leukemia K562 cell line resistant to adriamycin (K562/ADM) by means of one-step immunoaffinity chromatography using a monoclonal antibody against P-glycoprotein. The procedure was simple and efficiently yielded an electrophoretically homogeneous P-glycoprotein sample. By solubilization with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, the purified P-glycoprotein was found to have ATPase activity. This ATP hydrolysis may be coupled with the active efflux of anticancer drugs across the plasma membrane of multidrug-resistant cells. PMID- 2891710 TI - Linkages between the effects of taxol, colchicine, and GTP on tubulin polymerization. AB - A comparative study has been carried out of the effects of taxol on the polymerizations into microtubules of microtubule-associated protein-free tubulin, prepared by the modified Weisenberg procedure, and of the tubulin-colchicine complex into large aggregates. Taxol enhances, to a much greater extent, the stability of microtubules than that of the tubulin-colchicine polymers so that, with highly purified tubulin, assembly into microtubules takes place at 10 degrees C, even in the absence of exogenous GTP. The polymerization of tubulin colchicine requires both heat and GTP, and the process is reversed by cooling. These results indicate that in both systems polymerization is linked to interactions with taxol and GTP, the interplay of linkage free energies imparting the observed polymer stabilities. In the case of microtubule formation, the linkage free energy provided by taxol binding is approximately -3.0 kcal/mol of alpha-beta-tubulin dimer, whereas this quantity is reduced to approximately -0.5 kcal/mol in tubulin-colchicine, indicating the expenditure of much more binding free energy in the latter case for overcoming unfavorable factors, such as steric hindrance and geometric strain. The difference in the effect of GTP on the two polymerization processes reflects the respective abilities of the bindings of taxol to the two states of tubulin to overcome the loss of the linkage free energy of GTP binding. Analysis of the linkages leads to the conclusions that taxol need not change qualitatively the mechanism of microtubule assembly and that tubulin with the E-site unoccupied by nucleotide should have the capacity to form microtubules, the reaction being extremely weak. PMID- 2891713 TI - Human microsomal xenobiotic epoxide hydrolase. Complementary DNA sequence, complementary DNA-directed expression in COS-1 cells, and chromosomal localization. AB - A lambda gt11 expression library constructed from human liver mRNA was screened with an antibody against human microsomal xenobiotic epoxide hydrolase. The clone pheh32 contains an insert of 1742 base pairs with an open reading frame coding for a protein of 455 amino acids with a calculated Mr of 52,956. The nucleotide sequence is 77% similar to the previously reported rat xenobiotic epoxide hydrolase cDNA sequence. The deduced amino acid sequence of the human epoxide hydrolase is 80% similar to the previously reported rabbit and 84% similar to the deduced rat protein sequence. The NH2-terminal amino acids deduced from the human xenobiotic epoxide hydrolase cDNA are identical to the published 19 NH2-terminal amino acids of the purified human xenobiotic epoxide hydrolase protein. Northern blot analysis revealed a single mRNA band of 1.8 kilobases. Southern blot analysis indicated that there is only one gene copy/haploid genome. The human xenobiotic epoxide hydrolase gene was assigned to the long arm of human chromosome 1. Several restriction fragment length polymorphisms were observed with the human epoxide hydrolase cDNA. pheh32 was expressed as enzymatically active protein in cultured monkey kidney cells (COS-1). PMID- 2891712 TI - Purification and properties of the phosphorylated form of guanylate cyclase. AB - Guanylate cyclase is dephosphorylated in response to the interaction of egg peptides with a spermatozoan surface receptor (Suzuki, N., Shimomura, H., Radany, E. W., Ramarao, C. S., Ward, G. E., Bentley, J. K., and Garbers, D. L. (1984) J. Biol. Chem. 259, 14874-14879). Here, the phosphorylated form of guanylate cyclase was purified to apparent homogeneity from detergent-solubilized spermatozoan membranes by the use of GTP-agarose, DEAE-Sephacel, and concanavalin A-Sepharose chromatography. To prevent dephosphorylation of the enzyme during purification, glycerol (35%) was required in all buffers. Following purification, a single protein-staining band of Mr 160,000 was obtained on sodium dodecyl sulfate polyacrylamide gels. The final specific activity of the purified enzyme was 83 mumol of cyclic GMP formed/min/mg of protein at 30 degrees C, an activity 5-fold higher than that observed with the purified, dephosphorylated form of guanylate cyclase. A preparation containing protein phosphatase from spermatozoa, or highly purified alkaline phosphatase (from Escherichia coli), catalyzed the dephosphorylation of the enzyme; this resulted in a subsequent decrease in guanylate cyclase activity and a shift in the Mr from 160,000 to 150,000. The phosphate content of the high Mr form of the enzyme was 14.6 mol/mol protein whereas the phosphate content of the low Mr form was 1.6 mol/mol protein. All phosphate was localized on serine residues. The Mr 160,000 form of guanylate cyclase demonstrated positive cooperative kinetics with respect to MnGTP while the Mr 150,000 form displayed linear, Michaelis-Menten type kinetics. The phosphorylation state of the membrane form of guanylate cyclase, therefore, appears to dictate not only the absolute activity of the enzyme but also the degree of cooperative interaction between catalytic or GTP-binding sites. PMID- 2891715 TI - Glutamine and glutamate nitrogen exchangeable pools in cultured fibroblasts: a stable isotope study. AB - Glutamine's role as an energetic fuel has been extensively studied in the past using 14C- and 3H-labeled tracers in cultured human cells. Yet another prominent role of glutamine, that of a nitrogen shuttle, cannot be approached without an N tracer. We therefore used 15N-labeled glutamine and glutamate to address the following questions: 1) is it possible to study the exchangeable pools of intracellular free glutamine and glutamate nitrogen with stable isotope methods? and 2) to what extent is intracellular glutamine pool regulated by extracellular glutamine? We observed that: 1) intracellular [15N]-glutamine enrichment reached a plateau at 80% within 20 min of incubation in a buffer containing 0.7 mM pure 15N-glutamine and no glutamate; in contrast, intracellular 15N-glutamate enrichment rose only to 40% after 4 hours of incubation in a buffer containing 0.5 mM pure 15N-glutamate and no glutamine; 2) the cell-free glutamine content was tightly dependent on extracellular glutamine level, while the cell-free glutamate remained steady irrespective of the extracellular glutamate level; 3) the cells took up glutamine and glutamate against a concentration gradient; the rate of glutamine uptake accounted for 90% of the cell glutamine turnover rate; and 4) when cells were confronted with a glutamine-free medium, only one fourth of intracellular glutamine was derived from the exchangeable glutamate. We conclude that: 1) The size and turnover rate of the intracellular pool of free glutamine nitrogen are measureable using stable isotope methodology; 2) glutamine uptake from the extracellular medium accounts for most of glutamine turnover rate in cultured fibroblasts; and 3) intracellular free glutamate is divided up between several pools in cultured human fibroblasts. PMID- 2891714 TI - Temperature-dependent reversible assembly of taxol-treated microtubules. AB - Taxol is a plant alkaloid that binds to and strongly stabilizes microtubules. Taxol-treated microtubules resist depolymerization under a variety of conditions that readily disassemble untreated microtubules. We report here that taxol treated microtubules can be induced to disassemble by a combination of depolymerizating conditions. Reversible cycles of disassembly and reassembly were carried out using taxol-containing microtubules from calf brain and sea urchin eggs by shifting temperature in the presence of millimolar levels of Ca2+. Microtubules depolymerized completely, yielding dimers and ring-shaped oligomers as revealed by negative stain electron microscopy and Bio-Gel A-15m chromatography, and reassembled into well-formed microtubule polymer structures. Microtubule-associated proteins (MAPs), including species previously identified only by taxol-based purification such as MAP 1B and kinesin, were found to copurify with tubulin through reversible assembly cycles. To determine whether taxol remained bound to tubulin subunits, we subjected depolymerized taxol treated microtubule protein to Sephadex G-25 chromatography, and the fractions were assayed for taxol content by reverse-phase HPLC. Taxol was found to be dissociated from the depolymerized microtubules. Protein treated in this way was found to be competent to reassemble, but now required conditions comparable with those for protein that had never been exposed to taxol. Thus, the binding of taxol to tubulin can be reversed. This has implications for the mechanism of taxol action and for the purification of microtubules from a wide variety of sources for use in self-assembly experiments. PMID- 2891716 TI - Roles of protein kinases in neurotransmitter responses in Xenopus oocytes injected with rat brain mRNA. AB - Microinjection of rat brain mRNA in Xenopus oocytes induced acetylcholine, neurotensin, serotonin, and glutamate receptors in the cells. These receptors stimulate an intracellular reaction pathway, including G-protein activation, inositol trisphosphate (IP3) formation, and Ca2+-dependent Cl- channels. In the present study, we examined the roles of several protein kinases in these responses by means of inhibitors and activators of these kinases. Isoquinolinesulfonamides, inhibitors of protein kinases, caused no current responses and affected no receptor-mediated responses when injected into the oocytes at low doses (30-50 pmol), which inhibit cyclic nucleotide-dependent kinases or kinase C specifically, but abolished the receptor-mediated responses at a higher dose (300 pmol), which inhibit most protein kinases nonspecifically. Calmodulin inhibitors blocked the receptor-mediated responses strongly. Activation of cyclic nucleotide-dependent kinases or kinase C by injection of cAMP (or cGMP) or perfusion with phorbol esters caused no direct current responses but suppressed receptor-mediated responses. Current responses triggered by IP3 injection were not suppressed by these treatments. These results suggest that cAMP- (or cGMP-)dependent kinases or kinase C may not be involved in the pathway directly but may modulate it by inhibiting the initial part of the pathway (receptors, G-proteins, and/or phospholipase C), and they suggest that calmodulin may most likely be involved in the activation of Ca2+-dependent Cl- channels. PMID- 2891717 TI - Developmentally regulated primary glucocorticoid hormone induction of chick retinal glutamine synthetase mRNA. AB - We have characterized the glucocorticoid hormone induction of glutamine synthetase mRNA in embryonic chick retinal organ cultures by quantitative dot hybridization using a cDNA clone derived from chick retinal RNA. Hydrocortisone (Kapp = 3-4 nM) and dexamethasone (Kapp = 1-2 nM) produce an approximate 30-fold increase in glutamine synthetase mRNA after incubation of organ cultures derived from embryonic day 12 retinae with either hormone for 3 hr. Progesterone is a poor inducer. The glucocorticoid-mediated rise is rapid (t1/2 = 2-3 hr) and occurs in the presence of either of the protein synthesis inhibitors cycloheximide or puromycin, indicating that the induction is a primary or direct response to the hormone. However, the magnitude of the hormonal response observed in culture increases markedly during retinal development. These observations, coupled with the previously reported absence of a hormonal induction in embryonic liver, raise the possibility of a synergistic mechanism, involving tissue specific regulatory molecules in addition to the glucocorticoid hormone receptor, to explain the retinal-specific primary glucocorticoid hormone induction of glutamine synthetase mRNA. PMID- 2891718 TI - Peering through the windows of the brain. PMID- 2891719 TI - Hormonal evaluation of boys born with undescended testes during their first year of life. AB - We studied pituitary-gonadal function during the first year of life in 48 boys born with 56 undescended testes in order to test the hypotheses that functional insufficiency of the hypothalamo-pituitary-gonadal axis and disorders of testosterone (T) biosynthesis occur in such boys. Cryptorchidism persisted for longer than 1 yr in 29 boys (30 testes; group I), whereas spontaneous descent occurred in 19 boys (20 testes; group II), in 6 after the sixth month. A control group (group III) included 160 boys. Basal and peak LHRH-stimulated serum LH and FSH and basal serum T values were determined at 3, 6, and 12 months. Serum T, dihydrotestosterone (DHT), progesterone (P), 17-hydroxypregnenolone, 17 hydroxyprogesterone, dehydroepiandrosterone sulfate, and androstenedione before and after hCG administration were determined at age 1 yr. Comparing the 3 groups, cross-sectional evaluation revealed no significant differences in basal or peak LHRH-stimulated serum LH and FSH levels, except that basal serum LH levels were slightly higher in group II than in group III. Comparing groups I and II, longitudinal evaluation revealed similar basal and peak LHRH-stimulated serum LH and FSH values, with comparable changes with time. Basal serum T, DHT, and T precursor levels were similar in all three groups, with similar rises of T and DHT and variable minimal increases in androstenedione and dehydroepiandrosterone sulfate after hCG stimulation. We conclude that during the first year of life, boys with cryptorchidism have no functional insufficiency of the hypothalamo pituitary-gonadal axis or disorders in T biosynthesis. PMID- 2891720 TI - Treatment of acromegaly with the long-acting somatostatin analog SMS 201-995. AB - Current treatment of acromegaly (surgery, radiation, and bromocriptine) is often unsatisfactory, and a sizeable proportion of patients with this disease continue to have GH hypersecretion after all therapeutic modalities have been exhausted. Fifteen patients with active acromegaly (8 previously treated and 7 newly diagnosed) were treated with the long-acting somatostatin analog SMS 201-995 (Sandoz; 50-250 micrograms, sc, every 6-8 h for up to 21 months). The mean daily plasma GH concentration was significantly suppressed in 13 patients, and it became normal in 10. Two patients, however, did not have GH suppression by SMS 201-995 treatment alone; in 1, a significant decline in mean daily GH was achieved after the addition of bromocriptine. As expected, suppression of GH secretion was associated with normalization of plasma somatomedin-C values and significant clinical improvement. Plasma GH responses to synthetic GHRH-(1-44) and TRH were either abolished or blunted by SMS 201-995. Thyroid function remained normal, and glucose tolerance did not change. Significant shrinkage of pituitary tumors occurred in 7 previously untreated and 2 previously treated patients. Side-effects were minimal. SMS 201-995 is an effective agent for the treatment of acromegaly. Further studies are necessary to establish guidelines for identification of non-responders and to examine the effect of preoperative tumor shrinkage on subsequent surgical outcome. PMID- 2891721 TI - Differential effects of somatostatin (SRIH) and a SRIH analog, SMS 201-995, on the secretion of growth hormone and thyroid-stimulating hormone in man. AB - We compared the ability of SRIH and SRIH analog, SMS 201-995 (SMS), to inhibit stimulated GH and TSH secretion in men who received 120-min iv infusions of saline, SRIH (5, 50, and 500 micrograms/h), and SMS (3, 30, and 300 ng/kg.h) together with a bolus iv injection of GHRH (1 microgram/kg) and TRH (500 micrograms). Integrated GH secretion during the 60 min after GHRH plus TRH injection was decreased compared to that after saline by (mean +/- SE) 32 +/- 14% (P = 0.059), 78 +/- 5% (P less than 0.001), and 88 +/- 3% (P less than 0.001) during the 5, 50, and 500 micrograms/h SRIH infusions, and by 13 +/- 7% (P = NS), 50 +/- 15% (P less than 0.05), and 80 +/- 6% (P less than 0.001) during the 3, 30, and 300 ng/kg.h SMS infusions. In contrast, integrated TSH secretion was unaltered during the 5 micrograms/h SRIH and 3 ng/kg.h SMS infusions; it decreased by only 43 +/- 5% (P less than 0.001) and 66 +/- 4% (P less than 0.001) during the 50 and 500 micrograms/h SRIH infusions and by 33 +/- 8% (P less than 0.05) and 50 +/- 3% (P less than 0.001) during the 30 and 300 ng/kg.h SMS infusions. Analysis of the dose-response curves indicated approximately 10- and 5 fold greater potencies of SRIH and SMS, respectively, in inhibiting GH as compared to TSH secretion. These results quantify the effect of SRIH as an inhibitor of GH secretion and suggest that if SRIH has a physiological role in the inhibition of TSH secretion in man, it is limited to conditions associated with marked suppression of GH. PMID- 2891722 TI - Leydig cell function in infertile men with idiopathic oligospermic infertility. AB - To evaluate Leydig cell function in men with idiopathic oligospermic infertility and its eventual role in their infertility, plasma LH, testosterone (T), 17 hydroxyprogesterone (170HP), and estradiol levels as well as plasma T/LH and 170HP/T ratios were measured in 103 such men, subdivided into different groups according to their plasma FSH levels. The results were compared to results in normal young fertile men, the subgroup of men with idiopathic oligospermic infertility who within 12 months after consultation succeeded in impregnating their partner, infertile men with a history of undescended testes (excryptorchid men), and men with Klinefelter's syndrome. As a tentative parameter of androgen insensitivity, an androgen insensitivity index [LH (IU/L) X T (nMol/L)] was calculated. Although all men with idiopathic infertility had plasma T and LH levels within the normal range, LH levels increased and T/LH ratios decreased with increasing FSH levels, while the 170HP/T and estradiol/T ratios were independent of the FSH levels and T/LH ratios. The decreased T/LH ratios in the presence of normal T levels suggest compensated Leydig cell insufficiency, which possibly contributes to the infertility. Indeed, none of the men (n = 12) with normal FSH levels but a T/LH ratio lower than 1.50 achieved fatherhood within 12 months of follow-up, although all other hormonal parameters were within the normal range. During the same period 25 men with T/LH ratios greater than 1.50 succeeded in impregnating their partners (P less than 0.05). In infertile excryptorchid men and even more so in men with Klinefelter's syndrome, plasma T levels and T/LH ratios were significantly decreased, the decrease being greater than in patients with idiopathic azospermia with similar FSH levels. None of the excryptorchid men with normal FSH levels but T/LH ratios below 1.50 fathered a child during the follow-up study. We suggest that the T/LH ratio is an additional useful prognostic parameter of infertility. Plasma T levels were increased in 15% of patients with idiopathic infertility, but increased plasma LH together with increased T levels (increased androgen resistance index) were found in only 1 man. An increased index, however, was found in 6 azoospermic excryptorchid men and 4 of 28 men with Klinefelter's syndrome. Taken together these data suggest that this index is not a reliable parameter of androgen resistance. PMID- 2891723 TI - Antigenic analysis of fimbrial proteins from Moraxella bovis. AB - Fimbrial proteins were extracted from 15 isolates of Moraxella bovis, and antisera to each of the preparations were raised in rabbits. The antigenic relationships of the fimbriae were investigated by an enzyme-linked immunosorbent assay, tandem crossed immunoelectrophoresis, and a slide agglutination test. With all three methods there was a similar pattern of antigenic cross-reactivity among the fimbriae. The 15 isolates, together with 23 additional isolates, could be grouped into seven fimbrial serogroups. PMID- 2891724 TI - Efficacy of enzyme-linked immunosorbent assay for rapid diagnosis of Bordetella pertussis infection. AB - We examined the diagnostic efficacy of an enzyme-linked immunosorbent assay (ELISA) for class-specific antibodies to Bordetella pertussis in acute-phase sera collected from 1,240 patients with suspected pertussis. A total of 833 serum specimens (67%) yielded positive results. The proportion of positive results increased to 77% if a second (convalescent-phase) serum was also tested. By comparison, a bacterial agglutination test for B. pertussis antibodies was positive in only 21% of acute-phase specimens and 50% of paired specimens. The high proportion of acute-phase sera which were ELISA positive indicates that a measurable serologic response has usually occurred by the time the diagnosis is suspected. Thus, the ELISA is potentially the most rapid means of laboratory confirmation of B. pertussis infection. PMID- 2891725 TI - Regional distribution and density of Thy 1.1 in rat brain and its relation to subpopulations of neurons. AB - We have used a radioimmunohistochemical technique employing OX-7, a monoclonal antibody to rat Thy 1.1, to determine the regional distribution and density of Thy 1 in rat brain. Thy 1.1 was found to be unevenly distributed in rat brain with distinct regional differences related to the density of neuronal perikarya. This is consistent with the previously reported findings that Thy 1.1 is found primarily on neurons. However, the relative absence of Thy 1 in some cell body dense areas of the brain suggests that Thy 1 is expressed differentially on specific subsets of neurons which are abundant and widespread throughout the brain. PMID- 2891726 TI - Effects of long-chain, saturated fatty acids on membrane microviscosity and adrenocorticotropin responsiveness of human adrenocortical cells in vitro. AB - Adrenoleukodystrophy (ALD) and adrenomyeloneuropathy are inherited disorders in which long-chain, saturated fatty acids (LCFA) accumulate in various tissues. A mechanism by which LCFA cause the endocrine and neurological dysfunction characteristic of these diseases is proposed based on in vitro response of human adrenocortical cells to ACTH in the presence of various fatty acids. Human adrenocortical cells cultured in the presence of 5 microM hexacosanoic (C26:0) or lignoceric (C24:0) acids showed decreased basal and ACTH-stimulated cortisol release compared with cells cultured without exogenous fatty acids or in the presence of linoleic acid (C18:2). Measurement of fluorescence polarization demonstrates a significant increase in the membrane microviscosity of cells cultured in the presence of LCFA. It is hypothesized that cells exposed to LCFA have increased membrane microviscosity with a consequent decrease in their ability to respond to ACTH. This decrease in trophic support may contribute to the adrenal insufficiency and atrophy in patients with ALD. PMID- 2891727 TI - Identification of a new hereditary amyloidosis prealbumin variant, Tyr-77, and detection of the gene by DNA analysis. AB - In the last several years, five human plasma prealbumin (transthyretin) variants have been discovered in association with hereditary amyloidosis, a late-onset fatal disorder. We recently studied a patient of German descent with peripheral neuropathy and bowel dysfunction. Biopsied rectal tissue contained amyloid that stained with anti-human prealbumin. Amino acid sequence analysis of the patient's plasma prealbumin revealed both normal and variant prealbumin molecules, with the variant containing a tyrosine at position 77 instead of serine. We predicted a single nucleotide change in codon 77 of the variant prealbumin gene, which we then detected in the patient's DNA using the restriction enzyme SspI and a specifically tailored genomic prealbumin probe. DNA tests of other family members identified several gene carriers. This is the sixth prealbumin variant implicated in amyloidosis, and adds to the accumulating evidence that the prealbumin amyloidoses are more varied and prevalent than previously thought. PMID- 2891728 TI - Regulation of calcitonin gene transcription by vitamin D metabolites in vivo in the rat. AB - Calcitonin is secreted by the C cells of the thyroid in response to a raised serum calcium, and acts on bone to lower serum calcium. The C cells have specific receptors for the dihydroxymetabolite of vitamin D3, 1,25(OH)2D3. Moreover, calcitonin stimulates the synthesis of 1,25(OH)2D3 in the kidney. Parathyroid hormone (PTH), the third calciotrophic hormone, is also trophic to the renal synthesis of 1,25(OH)2D3, and in turn 1,25(OH)2D3 inhibits PTH gene transcription and synthesis. We report here the marked inhibition of calcitonin gene transcription by the injection of physiologically relevant doses of 1,25(OH)2D3 to normal rats that did not raise serum calcium. Calcitonin mRNA levels after 100 pmol 1,25(OH)2D3 decreased to 6% of basal at 6 h and 4% at 48 h, and a dose response showed a marked effect even after 12.5 pmol 1,25(OH)2D3, with no appreciably greater effect with larger doses (up to 200 pmol). Control genes, actin, thyroglobulin (thyroid follicular cells), somatostatin (thyroid C-cells) were not affected by 1,25(OH)2D3. Gel blots showed that 1,25(OH)2D3 decreased calcitonin mRNA levels without any change in its size. In vitro nuclear transcription showed that 1,25(OH)2D3-treated (100 pmol) rats' calcitonin transcription was 10% of control, while thyroglobulin and actin were 100%. We propose that calcium is the major regulator of PTH and calcitonin secretion, while 1,25(OH)2D3 is an important regulator of PTH and calcitonin gene transcription. We believe this to be the first demonstration of an effect of 1,25(OH)2D3 on the C cells thereby establishing a new target organ and site of action of vitamin D. Calcitonin is trophic to 1,25(OH)2D3 synthesis, which in turn inhibits calcitonin synthesis, which are the components of a new endocrinological feedback loop. PMID- 2891730 TI - Serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (gamma-GT) activities in north London blood donors. AB - Serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (gamma-GT) activities were measured in over 2000 north London blood donors. The results were compared with those from the United States. The percentage of the total donor population with ALT activities above 40 IU/l in 1986 was greater than that found in our earlier studies in 1973 and 1982 (4.6% compared with 2.8% and 3.1%, respectively). There was a noticeable difference in the ALT distribution between male and female donors: mean +2.25 SD for male donors was 55.3 IU/l, while that for female donors was 30.8 IU/l at 37 degrees C. In stability studies the optimal temperature for short term storage (10 days) was 4 degrees C (6.4% loss of activity after 10 days). Surprisingly, storage at lower temperatures (-35 degrees C and -80 degrees C) resulted in greater loss of activity. PMID- 2891731 TI - Comparison of nifedipine and captopril as third-line agents in hypertensive patients uncontrolled with beta-blocker and diuretic therapy. AB - The effect of adding either nifedipine or captopril as third-line agents was studied in a single-blind crossover fashion in 24 patients with essential hypertension uncontrolled by combination beta blocker and diuretic therapy. Nineteen patients completed both phases of the study. The mean initial sitting blood pressure before the addition of nifedipine was 164/109 mm Hg and captopril 165/108 mm Hg. Both nifedipine and captopril produced further significant reductions in both sitting and standing blood pressure, 47% of the captopril treated patients achieving target blood pressure of less than 160/95 mm Hg compared with 67% with nifedipine. Further increase in the dosage resulted in 63% of the captopril- and 81% of the nifedipine-treated patients achieving target blood pressure. There were, however, no statistically significant differences in the mean fall in blood pressure or in the number of patients obtaining target pressure at the end of each treatment period. Captopril treatment also resulted in a small reduction of pulse rate, and, although pulse rates rose with nifedipine, these changes were not significant. Both treatments were generally well tolerated, and serious side effects were not reported. Both nifedipine and captopril were effective and well tolerated as third-line antihypertensive agents. PMID- 2891729 TI - Close association between interleukin 2 receptor mRNA expression and human T cell leukemia/lymphoma virus type I viral RNA expression in short-term cultured leukemic cells from adult T cell leukemia patients. AB - Human T cell leukemia/lymphoma (T-lymphotropic) virus type I (HTLV-I) infection has been considered to be closely associated with the leukemogenesis of adult T cell leukemia (ATL), in which interleukin 2 (IL-2) receptors are abnormally expressed. In this study, however, Southern blot analysis revealed no gross rearrangement or obvious amplification of the IL-2 receptor gene in ATL leukemic cells, indicating that abnormal IL-2 receptor expression in ATL is not due to the structural change of its gene. Hence, we studied the expression of the IL-2 receptor and HTLV-I at the RNA level during short-term cultures of leukemic cells from 9 ATL patients. Cytoplasmic dot hybridization and Northern hybridization revealed that fresh leukemic cells from seven of nine patients expressed a small amount of IL-2 receptor mRNA but HTLV-I RNA was undetectable in all cases. After cultures for up to 7 d, both IL-2 receptor mRNA and HTLV-I RNA (including pX message) expression concomitantly increased, whereas the amounts of other cellular genes, except for beta-actin, did not. The increases in their RNA expression were inhibited by early addition (within 12 h after the beginning of the culture) of cycloheximide, indicating that these increases are mediated by newly synthesized protein(s). These results strongly suggested that IL-2 receptor expression is closely associated with HTLV-I expression in leukemic cells from ATL patients. PMID- 2891732 TI - Functional topography of the rat hypothalamic dopamine neuron systems: retrograde tracing and immunohistochemical study. AB - The origins of the dopamine (DA)-containing nerve terminals in the external layer of the median eminence and in the neurointermediate pituitary were determined in rats by a combination of retrograde labeling with wheat germ agglutinin (WGA) and immunohistochemistry for tyrosine hydroxylase (TH). Biotinylated WGA (b-WGA) was injected into the posterior pituitary (group 1) and into the median eminence (group 2). In group 1 animals, all the magnocellular neurons of the paraventricular, supraoptic, and accessory nuclei, and many parvicellular neurons in the rostral periventricular region (RPR) were labeled with WGA. In group 2 animals, many neurons were labeled in the arcuate nucleus and the RPR, and in a small population of the preoptic-septal region. In group 1 animals, about 39% of TH neurons in the RPR were labeled with WGA, whereas only a few TH neurons (1%) in the arcuate nucleus were labeled with WGA. In group 2 animals, on the contrary, almost all TH neurons (73%) in the arcuate nucleus carried WGA, whereas in the RPR, only some of the TH neurons (19%) were labeled with WGA. It is concluded that DA neurons involved in the hypothalamic-anterior pituitary axis are located in the arcuate nucleus; those involved in neuro-intermediate lobe function in the RPR. PMID- 2891733 TI - Evidence for coexistence of GABA and dopamine in neurons of the rat olfactory bulb. AB - Immunoreactivities for gamma-aminobutyric acid (GABA) and the dopamine synthesizing enzyme tyrosine hydroxylase (TH) were localized ultrastructurally and colocalized at the light microscopic level in neurons of the rat main olfactory bulb. By means of a simultaneous indirect immunofluorescence technique, GABA and TH immunoreactivities were found to coexist in a large number of neurons in the glomerular and external plexiform layers. Virtually all the TH immunoreactive periglomerular neurons also contained GABA immunoreactivity (GABA I) while there was an additional number of GABA-immunoreactive periglomerular cells (27%) which did not contain TH immunoreactivity (TH-I). In contrast, the numerous tufted-type neurons in the glomerular and superficial external plexiform layers which contained TH-I did not contain GABA-I. In the external plexiform layer (EPL), 41% of the immunoreactive neurons contained GABA-I alone, 24% contained TH-I alone, and 35% contained both. EPL neurons containing GABA-I only or both GABA-I and TH-I never exhibited tufted cell morphological characteristics and were generally of the short-axon type. Electron microscopic examination of GABA-I and TH-I elements in the glomerular layer detected morphologically similar periglomerular perikarya and intraglomerular processes immunoreactive for each substance and other neurons and processes of the same type containing neither GABA-I or TH-I. These data indicate that the classical neurotransmitters GABA and dopamine coexist in large numbers of neurons in the rat main olfactory bulb including characteristic periglomerular cells and certain other local-circuit neuronal types. PMID- 2891735 TI - Fulminant systemic necrotizing arteritis: CT findings. AB - Fulminant necrotizing arteritis can be a rapidly fatal disease with protean manifestations often suggesting other diagnoses. We present two cases with angiographic and CT correlation and discuss CT findings that are suggestive of the diagnosis. PMID- 2891736 TI - Cognitive-behavioral treatment of women's body-image dissatisfaction. PMID- 2891737 TI - Safety of the entomopathogenic fungus Lagenidium giganteum (Oomycetes: Lagenidiales) to mammals. PMID- 2891734 TI - Renal handling of taurine, L-alanine, L-glutamate and D-glucose in Opsanus tau: studies on isolated brush border membrane vesicles. AB - Renal brush border membrane vesicles (bbmv) from the aglomerular toadfish (Opsanus tau), isolated by differential precipitation, were tested for their ability to actively translocate (i) taurine, known to be secreted by the kidney of several marine teleosts, and (ii) L-alanine, L-glutamic acid, and D-glucose, solutes that are normally reabsorbed in the filtering nephron. Vesicular taurine uptake displayed a Na+ dependence. Transport was greatest under conditions of an inward-directed Na+ gradient, but a significant stimulation by Na+ over K+ could also be observed in the absence of a salt gradient. At high extravesicular K+, the addition of valinomycin reduced taurine uptake. Na+-dependent 3H-taurine flux was almost completely inhibited by non-labeled taurine (tracer replacement) or beta-alanine, but was unaffected by L-alanine. Replacement of medium chloride by SCN- or NO3- in the presence of Na+ resulted in significantly lower uptake rates under both anion gradient and anion equilibrium conditions, whereas Br- could almost fully substitute for the stimulatory Cl- action. These results indicate the presence of an electrogenic Na+-cotransport mechanism with specificity for beta-amino acids in the toadfish renal brush border. Whether the system under physiological conditions mediates reabsorption or secretion of taurine remains to be determined. Toadfish bbmv also translocated L-alanine and L-glutamic acid in a Na+-dependent manner. Possible roles for these most likely reabsorptive transport systems in a non-filtering kidney are discussed. D-glucose uptake, however, appeared to occur via Na+-independent pathways, since it was not affected by phlorizin in the presence of Na+, or by Na+ replacement. PMID- 2891738 TI - The pharmacokinetics and pharmacodynamics of terfenadine in children. AB - The pharmacokinetics and pharmacodynamics of terfenadine were studied in 13 children with allergic rhinitis, mean age 7.45 +/- 0.54 SEM years. Serum concentrations of the active carboxylic acid metabolite of terfenadine (terfenadine metabolite I) were measured before and hourly for 8 hours after administration of a single dose of terfenadine suspension. The mean maximum serum concentration of terfenadine metabolite I, 242 +/- 28 ng/ml, occurred at 2.3 +/- 0.2 hours; the mean serum half-life value was 2.0 +/- 0.1 hours. Wheals and flares after epicutaneous tests with histamine phosphate, 1.0 mg/ml and 0.2 mg/ml, were significantly suppressed from 1 to 8 hours after the terfenadine dose compared to predose values. Maximum wheal suppression occurred at from 3 to 6 hours. Itching was completely suppressed for 8 hours. No serious adverse effects occurred. Terfenadine in children appears to be well absorbed, and its carboxylic acid metabolite has a short serum elimination half-life. The duration of its suppressive effect on the histamine-induced wheal and flare greatly exceeds that expected from consideration of serum terfenadine metabolite I concentrations. PMID- 2891739 TI - [Metipranolol 0.1%: effect of a single dose on the nycthemeral pressure curve in an eye with chronic primary open-angle glaucoma]. AB - A double blind randomised study was made to compare the efficiency in decreasing intra ocular pressure of Metipranolol 0.1% or 0.3% versus placebo in three groups of 15 patients with chronic open angle glaucoma with or without visual field defects. The results demonstrate that Metipranolol 0.1% significantly lowers the intra ocular pressure in comparison with placebo. But this lowering is less that the one with 0.3% and is markedly reduced after 9 hours. The action of Metipranolol 0.3% is more durable and is still observed at 24 hours with a drop of nearly 20% in comparison with the initial intra ocular pressure. In the three groups, no significant variation of pulse and arterial pressure could be noticed during this 24 hours study. PMID- 2891740 TI - [Mid-term results of a double-blind study comparing metipranolol to timolol in the treatment of primary open-angle glaucoma]. AB - A study on 26 patients with chronic angle glaucoma was completed after 17 weeks. The IOP was satisfactorily stabilized on patients treated with Metipranolol drops. In the Timolol group, the IOP rose again after the 9th week and, at the completion of the study, the difference between the averages of the two groups is significant. No systemic effect was noted as well in the Metipranolol group as in the Timolol group. PMID- 2891741 TI - Reaching optimum function is realistic goal for elderly. PMID- 2891742 TI - A comparison of the pharmacological properties of the novel tricyclic antidepressant lofepramine with its major metabolite, desipramine: a review. AB - The effects of the novel tricyclic antidepressant lofepramine were compared with that of its principal metabolite desipramine. In double-bind clinical trials, lofepramine has been shown to be as effective as desipramine and other comparator tricyclic antidepressants in the treatment of endogenous and reactive depression, but there are some differences between them. Thus the acute toxicity of lofepramine is approximately one-fifth that of its metabolite; lofepramine is a less potent muscarinic receptor antagonist than desipramine (verified by clinical studies in volunteers and depressed patients); lofepramine is less likely to produce conduction defects than desipramine. Neurochemical studies show that both lofepramine and its metabolite are potent noradrenaline uptake inhibitors in vitro and evidence is presented to suggest that lofepramine may release this amine following chronic administration in vivo; both drugs slightly increase serotonin turnover under these conditions and down-regulate cortical beta adrenoceptor function. Unlike desipramine and most clinically effective antidepressants, lofepramine was inactive in attenuating the hyperactivity of olfactory bulbectomized rats in the "open field" apparatus, and in reversing acute clonidine induced hypomotility. From such tests it appears unlikely that the active metabolite, desipramine, is formed in the brain in sufficient concentrations after chronic lofepramine administration to make a substantial contribution towards the pharmacological activity of the parent compound. PMID- 2891743 TI - Characterization of antisera to glutamate and aspartate. AB - Antisera were raised in rabbits against glutamate (Glu) and aspartate (Asp) conjugated to the invertebrate carrier protein hemocyanin (HC) with glutaraldehyde (GA). The antisera were characterized by testing their immunocytochemical staining properties on sections cut at the level of the ventral cochlear nucleus (VCN) from fixed brains of normal rats after absorption with conjugates of compounds structurally similar and biologically relevant to Glu and Asp. Optimal staining with Glu antiserum was obtained at a dilution of 1:10,000 and was completely blocked by 303 micrograms/ml of the Glu-HC conjugate. No crossreactivity with any of 11 compounds tested was observed. Optimal staining with the Asp antiserum was obtained at 1:8000 dilution and was completely blocked by 225 micrograms/ml of the Asp-HC conjugate. Of 10 compounds tested for crossreactivity, only L-asparagine demonstrated a measurable (about 10%) crossreactivity with the Asp antiserum. The specificity of the two antisera was also tested by immunoblot analysis against 11 compounds conjugated to HC with GA. Listed in order of staining intensity, from greatest to least, conjugates that reacted with the Glu antiserum were Glu greater than Gly-Glu greater than Asp-Glu = Asp greater than N-carbamyl (NC)-Glu greater than Asn = Gln = GABA. Conjugates that reacted with the Asp antiserum, in order of decreasing staining intensity, were Asp greater than Glu-Asp = Asn greater than Gly-Asp greater than Glu. No other compounds tested for crossreactivity reacted with the two antisera in the immunoblot analysis. Glu-like immunoreactivity in rat dorsal root ganglia and somatosensory cortex, and the comparative distribution of Glu- and Asp-like immunoreactivities in the latter tissue, are presented as examples of staining patterns obtained with the two antisera. PMID- 2891744 TI - Light microscopic visualization of the reaction product of cerium used for localization of peroxisomal oxidases. AB - The reaction product of cerium used for localization of peroxisomal oxidases is highly electron-dense but lacks sufficient contrast at the light microscopic level. We describe two methods for converting the reaction product of cerium to colored compounds visible by light microscopy. The first method is based on 3,3' diaminobenzidine (DAB) amplification of transition metal compounds, of which cerium is one. Sections of glutaraldehyde-fixed rat liver or kidney are incubated first in media for various oxidases containing CeCl3, followed by treatment with DAB in Na acetate buffer, pH 5.3. To prevent any interference by the peroxidatic activity of catalase, NaN3 or Na pyruvate is added to the DAB amplification medium. Staining with DAB can be further intensified with NiCl2 or CoCl2. The second method is based on the conversion of the cerium reaction product with alkaline lead citrate and the final visualization of the lead compound with ammonium sulfide. These methods allow the evaluation of large sections for peroxisomal oxidases by light microscopy, making close correlation between light and electron microscopy possible. PMID- 2891745 TI - Three-color immunofluorescence histochemistry allowing triple labeling within a single section. AB - We describe a procedure for simultaneous immunohistochemical localization of three different neuropeptides, neurotransmitters, or neurotransmitter enzymes within one and the same tissue section and present a number of examples of its application within the brain and periphery. Primary antibodies from three different species were bound to three different neurochemical substances within the same section and were then reacted with three appropriate species-specific antisera conjugated with fluorescein, rhodamine/Texas red, or biotin. The biotinylated secondary antiserum was subsequently reacted with diethylaminocoumarin (DAMC) conjugated to avidin. This combination resulted in green, red, and blue fluorescent labeling of each antigen, respectively. Each fluorescent marker was viewed and photographed discretely using appropriate excitation and suppression filter combinations. The method is well suited for analyzing instances of multiple coexistence at both the level of the cell soma and within terminal regions. More broadly, the feasibility of three-color immunofluorescence histochemistry extends the range with which antigen localization can be used to investigate the morphological bases of relationships and interactions between immunohistochemically characterized neuronal elements. PMID- 2891746 TI - Immunocytochemical localization of gamma-glutamyltranspeptidase during fetal development of mouse kidney. AB - In the fully developed kidney, gamma-glutamyltranspeptidase is localized predominantly to the apical plasma membrane of the proximal tubules. The appearance of this activity during murine fetal nephrogenesis was quantitated using a sensitive fluorometric assay, and development of membrane polarity was assessed by immunocytochemistry. Specific activity of the transpeptidase in 13 day fetal kidney was approximately 1 mU/mg protein. Between 13-21 days of gestation, total transpeptidase activity increased 7500-fold, whereas specific activity increased 50-fold. At 13 days of gestation, gamma-glutamyltranspeptidase immunoreactivity is localized to the apical surfaces of developing renal vesicles and the proximal segment of the S-shaped tubules. The organized cell structures have tight tubular junctions but lack a well-defined brush-border membrane. By 15 days of gestation, immunostaining of the apical surface of developing proximal segments is more prominent, and slight reactivity of the basolateral membrane is evident. By 17 days of gestation, the kidney is organized into discrete zones. The large increase in gamma-glutamyltranspeptidase activity correlates with the appearance of increased immunostaining of the developing brush-border membranes of the proximal tubules contained in the inner cortex. A very similar although somewhat delayed pattern of appearance of transpeptidase activity and immunostaining was observed in metanephric organ culture. Induction of proximal tubular cyst formation had no effect on the increase in transpeptidase activity that occurred during organotypic nephrogenesis. PMID- 2891747 TI - Distribution of monoamine-containing neurons in the brain of a teleost, Carassius auratus (Cyprinidae). AB - The occurrence and distribution of monoamine-(MA) containing neurons and fibres in the brain of Carassius was investigated by formaldehyde-induced fluorescence (FIF) histochemistry (Falck-Hillarp technique). Many brightly green-fluorescent nerve cell perikarya were found in the nucleus dorsolateralis and ventromedialis, in the nucleus posterioris periventricularis, in the nucleus recessus lateralis and posterioris. They also occurred in the mesencephalic nucleus lateralis valvulae, in the metencephalic nucleus gustatorius secundus and near the ventricular borders of the facial and vagal lobes in the myelencephalon. Many fluorescent fibres and nerve terminals were localized in the frontal and medio lateral parts of the telencephalon, showing fluorescent connections to the caudal parts. In the diencephalon, MA-fibres branched in a horizontal and ventral tract, leading to the medulla oblongata and the hypothalamic nuclei, respectively. There were laterally situated fibres connecting the hypothalamic nuclei with the medulla and the nucleus gustatorius secundus. Many fluorescent fibres were found in the middle layers of the tectum opticum, in the torus semicircularis, in the lobus inferior and in the medulla oblongata. Considerably fewer fibres occurred in the corpus cerebelli and in the dorsal parts of the hindbrain lobes. These results are compared with the MA-system in the brains of other fish. PMID- 2891748 TI - The role of antiseptics in the management of patients with long-term indwelling bladder catheters. PMID- 2891749 TI - Nosocomial infections on nursing units with floors cleaned with a disinfectant compared with detergent. AB - Nosocomial infections on eight acute care nursing units in a tertiary care hospital was compared between two 3-month periods in which floors were cleaned with either disinfectant or detergent. Personnel performing infection surveillance were unaware of the cleaning product used. Surface cultures from selected floor sites were obtained at 3 and 6 months to assess microbial contamination. The combined nosocomial infection rate for the eight wards did not differ between disinfectant (8.0/100 patient discharges) and detergent (7.1/100). For individual wards, a significant difference in nosocomial infection rate between the two periods was observed in only one ward, favouring the detergent. No differences in floor contamination were observed. PMID- 2891750 TI - A new safety system for air filtration in clinical suction apparatus. AB - The design and development of a low cost differential pressure indicator giving continual pressure comparison across the substance of an air filter is described. A hazard warning is given when the differential pressure rises above a pre-set value proportional to significant loss of filter efficiency. The differential pressure indicator affords increased protection against infection associated with the use of suction apparatus and allows a net saving in expenditure by ensuring optimum use of integral air filters. PMID- 2891751 TI - Investigation of Clostridium difficile diarrhoea in a district general hospital: room for improvement? AB - A retrospective survey of case-notes was carried out on all patients investigated for possible Clostridium difficile diarrhoea during a 1-month period at a district general hospital. Seven of 29 patients probably had the disease, but no case of pseudomembranous colitis was documented. Delay in reporting and discrepancies between culture and cytotoxin results contributed in several cases to mismanagement. In 14 of 16 cases negative by culture and cytotoxin, a plausible non-microbiological case for diarrhoea was found, including aperients in six. PMID- 2891752 TI - An outbreak of Salmonella typhimurium gastroenteritis in a psychiatric hospital. AB - An outbreak of Salmonella typhimurium (phage type 12) infection involving 11 patients and 12 members of staff occurred in a psychiatric hospital in Merseyside during a 3-week period in September and October 1984. Bacteraemia did not occur in any patients, those affected having a mild self-limiting diarrhoea. The source of the organism remained unknown but the most probable means of transmission was by person to person contact. The outbreak was controlled by transferring affected patients to an isolation ward. Staff were encouraged to report gastrointestinal symptoms and remain off work until symptom free or until the results of cultures were known. The problems of managing the outbreak are discussed. PMID- 2891753 TI - Methicillin resistant Staphylococcus aureus; the role of antisepsis in the control of an outbreak. AB - Between February 1983 and September 1985, an outbreak of methicillin-resistant Staphylococcus aureus involving 151 patients and staff occurred in a district general hospital. At its peak, 43 cases occurred in 3 months. Sixty-two patients suffered morbidity and two died. Conventional isolation techniques and once-daily whole body washing of affected patients with triclosan successfully controlled the outbreak. PMID- 2891754 TI - Metronidazole prophylaxis in acute mural appendicitis: failure of a single intra operative infusion to reduce wound infection. AB - The efficacy of a single 500 mg intravenous intra-operative dose of metronidazole in the prevention of postoperative wound infection, following appendicectomy for acute mural appendicitis, was studied in a prospective randomized placebo controlled trial. Fourteen of the 96 patients (14.6%) in the metronidazole group and 13 of the 94 in the placebo group (13.8%) developed postoperative wound infection. Late sepsis was noted in 4 out of the 96 patients in the metronidazole group and in one of the 94 patients in the placebo group. This study suggests that a single intra-operative dose of metronidazole dose not reduce the incidence of postoperative wound infection following appendicectomy for acute mural appendicitis. PMID- 2891755 TI - Endemic occurrence of Acinetobacter calcoaceticus biovar anitratus in an intensive care unit. AB - One strain of Acinetobacter calcoaceticus biovar anitratus caused colonization of 111 patients admitted to an intensive care unit (ICU) during a 2-year period. All patients were intubated and had received antibiotic therapy prior to colonization. Morbidity due to the organism was about 1%. The colonization rate showed a decreasing trend during the study period, but no seasonal variation. The strain was found in the air in a low concentration and on the hands of 8-13% of the members of the staff. No chronic carriers were found. PMID- 2891756 TI - Comparison of flow rates into vented and non-vented urinary drainage bags: possible relevance to infection. AB - Tests on vented and non-vented urinary drainage bags were carried out to establish if differences existed in the flow of fluid into them and whether air bubbles and air trapping were affected by venting. At flow rates of 3-12 ml sec-1 there was consistent flow into the vented bag until it was full. There was no air trapping in the bag, and no retrograde flow of air bubbles or fluid up the tube. Flow rates into non-vented bags were strongly affected by air in the drainage tube but, if this cleared, the flow rate was high until the bags were nearly full, at which time air was pushed into the tube. If air remained in the tube the flow rate was reduced. The non-vented bags required a higher pressure in the drainage tube to fill them than the vented bags, and allowed air bubbles to ascend from the bag up the drainage tube. PMID- 2891757 TI - Corynebacterium diphtheriae in the environment of carriers and patients. AB - A total of 533 throat and nasopharyngeal cultures were obtained from 328 staff who nursed cases of diphtheria and carriers of Corynebacterium diphtheriae; none yielded C. diphtheriae. Only one out of 189 environmental samples relating to 22 patients and carriers was positive. In addition, one carrier with chronic skin disease was found to have widespread colonization with C. diphtheriae. Several samples both from his hospital room and home yielded C. diphtheriae, indicating that he was a 'disperser.' PMID- 2891758 TI - 'Tegaderm' dressings prevent recolonization of chlorhexidine-treated skin. AB - 'Tegaderm', a semi-permeable, self-adhesive dressing made of polyurethane film, applied to intact upper arm skin in Intensive Care Unit (ICU) patients reduced the aerobic skin flora compared to adjacent exposed skin sites. We also applied 'Tegaderm' to skin disinfected with chlorhexidine; the aerobic skin flora remained unchanged at a low level for 5 days. PMID- 2891759 TI - Comparative testing of disinfectants against Mycobacterium tuberculosis and Mycobacterium terrae in a quantitative suspension test. AB - In order to establish a quantitative suspension test to assess the tuberculocidal activity of disinfectants, comparative tests were carried out with a variant of the Dutch Standard Suspension Test using Mycobacterium tuberculosis and Mycobacterium terrae as the test organisms. The results indicate that both species have a similar susceptibility towards disinfectants. Because of this and since M. terrae is a relatively fast growing organism with a low pathogenic potential, it is recommended that this species be used for determining the tuberculocidal potential of new products. PMID- 2891760 TI - Microbial contamination associated with routine aseptic practice. AB - We have studied the rate of fortuitous contamination associated with routine aseptic technique under operational conditions. Stainless steel strips, as simulators of surgical instruments, were contained in sterilized surgical packs and assayed by nursing personnel during surgical and other invasive procedures at three different hospitals. The rates of contamination observed for the 36 investigators ranged from 0% to 11.3%, with an overall rate of 2.7%. Assays conducted in a clean room environment, under conditions approaching industrial sterility standards, showed a contamination rate of 0.16%. We concluded that aseptic practices, as routinely performed without any noticeable breaks or transgressions, do not guarantee sterility. The concept of surgical sterility implies low level, but measurable, microbial contamination. PMID- 2891762 TI - An assessment of the performance of a glass bead sterilizer. AB - The performance of a simple glass bead sterilizer designed for use with hand held instruments such as in chiropody surgeries was studied and found to be generally within specification. However, we recommend certain precautions during use. PMID- 2891761 TI - The antimicrobial activity of protamine and polybrene. AB - Polybrene and protamine have broad antimicrobial activity and may be useful as topical agents. PMID- 2891763 TI - Breast milk and methicillin-resistant Staphylococcus aureus. PMID- 2891764 TI - Use of 'Signal system' (Oxoid) for diagnosing infection in continuous ambulatory peritoneal dialysis (CAPD) PMID- 2891765 TI - Pseudomonas cepacia pseudobacteraemia associated with a contaminated blood gas analyzer. PMID- 2891766 TI - Inhibition of transformed T cell growth in vitro by monoclonal antibodies directed against distinct activating molecules. AB - Stimulatory of antigen-specific murine T cell hybridomas with the appropriate antigen has been shown to cause lymphokine secretion and inhibition of spontaneous cell growth. In this study, the effect of cellular activation on the growth of transformed T cells, of known or unknown antigen specificity, was explored with stimulatory monoclonal antibodies (mAb) that recognize nonclonally distributed T cell surface molecules. Anti-CD3 antibodies stimulated interleukin 2 (IL-2) secretion while they inhibited murine and human T cell tumor growth in vitro. Both responses required external cross-linking of the anti-CD3 antibodies. Activation via two molecules that are not physically associated with the T cell antigen receptor, Thy-1 and Ly-6, also inhibited transformed T cell growth while inducing IL-2 secretion. Notably, an anti-Thy-1 mAb that did not cause the transformed T cells to secrete lymphokines failed to affect their growth, and in fact blocked the growth inhibition induced by the stimulatory mAb. Regardless of which stimulating mAb was used, IL-2 production and cell growth were inversely proportional, manifesting similar antibody dose-response curves. Activation of a T cell hybridoma with stimulatory mAb resulted in rapid lysis, as evidenced by the release of 51Cr and lactate dehydrogenase. Cell cycle analysis demonstrated that cellular activation was accompanied by a cell cycle block between the G1 and S phases, and probably a slowing of the transit of cells already in S. These results demonstrate that the growth of a spectrum of neoplastic T cells, murine and human, can be inhibited by what are normally growth-promoting signals for non transformed T cells. PMID- 2891768 TI - Regulation of T cell clone function via CD4 and CD8 molecules. Anti-CD4 can mediate two distinct inhibitory activities. AB - The functional effects resulting from CD4 and CD8 perturbation were analyzed by using a CD4+CD8+ clone and anti-CD4 and anti-CD8 monoclonal antibodies. Perturbation of CD8, but not CD4, by soluble antibody resulted in the inhibition of CD3-T cell receptor (CD3-Ti) triggering as determined by flow cytometric measurements of intracellular free Ca2+ concentrations. In addition, the CD3-T cell receptor-mediated cytotoxic function of the CD4+CD8+ clone was inhibited by anti-CD8, but not by anti-CD4. These results suggest that CD8, but not CD4, was functionally associated with CD3-Ti on the CD4+CD8+ clone. Although CD4 perturbation did not affect CD3-Ti-mediated activities, it resulted in the inhibition of the interleukin 2-dependent proliferation of this clone. Perturbation of CD8 did not affect the interleukin 2 dependent proliferation of the CD4+CD8+ clone. On the other hand, CD4 molecules of another CD4+CD8- clone unlike those of the CD4+CD8+ clone, were clearly linked to T cell receptor function. These results indicate that CD4 perturbation can result in two distinct regulatory activities; one involves the regulation of CD3-T cell receptor function, whereas the other is not directly associated with CD3-T cell antigen receptor function. The data are also consistent with the notion that CD4 and CD8 do not merely function as recognition and adhesion elements for accessory cell major histocompatibility complex molecules, but have a direct role in the regulation of T cell activation. PMID- 2891767 TI - Human T cells can be directed to lyse tumor targets through the alternative activation/T11-E rosette receptor pathway. AB - We investigated the ability of human T cells to be directed to lyse murine and human tumor targets by antibodies (Ab) to the T11-E rosette (CD2) receptor. We found that the human cytotoxic T lymphocyte clone TBI-6, which is specific for the Epstein-Barr virus-transformed cell line, CM-EBV, could be directed to lyse the Fc receptor-positive murine tumor P388D1, by the combination of anti-T11(2) plus anti-T11(3) Ab. This activation and lysis was demonstrable only with an Fc receptor expressing tumor target and only with those Ab or with anti-T3 (CD3) Ab but not with other anti-T11 Ab or other Ab directed against surface structures on the clone. We therefore constructed heterodimeric Ab consisting of anti-T11(2) or anti-T11(3) Ab and the J5 anti-common acute lymphoblastic leukemic antigen (anti CALLA) Ab. The purity and retained functional properties of the dimers were demonstrated by sodium dodecyl sulfate-polyacrylamide gels, fluorescence activated cell sorter analysis on relevant cells, and by the ability of these conjugates to activate human peripheral blood lymphocytes to proliferate. These heterodimeric Ab conjugates were shown to be able to direct the lysis of CALLA+ targets by TBI-6. The specificity of this lysis was demonstrated by the inability of these heterodimers to direct the lysis of CALLA- targets by the cytotoxic T lymphocyte clone, and by the ability of excess free J5, but not an irrelevant Ab of the same isotype, to block this type of lysis. The potential clinical significance of these reagents is discussed. PMID- 2891769 TI - Heterogeneity of steroid 21-hydroxylase genes in classical congenital adrenal hyperplasia. AB - Careful genotyping of three families, each having a member with classical salt losing steroid 21-hydroxylase deficiency, has allowed identification of carrier haplotypes. Digestion with TaqI or EcoRI and probing with a cDNA probe for the 21 hydroxylase genes (pC21/3c) revealed that all six affected haplotypes are abnormal with at least EcoRI. The data suggest that there is extreme polymorphism of the 21-hydroxylase genes and that dysfunction may result from several different abnormalities. PMID- 2891770 TI - Identification of Bacillus thuringiensis strains toxic to mosquitoes recently isolated in Israel. PMID- 2891771 TI - Characterization of Citrobacter diversus strains causing neonatal meningitis. AB - We studied 17 strains of Citrobacter diversus isolated from the cerebrospinal fluid of infants with meningitis and compared these strains with 21 strains isolated from other body sites. The two groups of strains were similar with respect to biotype, piliation, hemolysin production, and resistance to the killing effects of serum. By using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we found that 14 (82%) of 17 strains from cerebrospinal fluid, but only two (10%) of 21 strains isolated from other body sites, possessed a minor outer membrane protein with a molecular weight of 32,000 (P less than .0001). This protein may serve as a marker for strains of C. diversus that are likely to cause meningitis or brain abscess in human neonates. PMID- 2891772 TI - Simultaneous infection with the human immunodeficiency virus and HTLV-1 in a patient with AIDS. PMID- 2891773 TI - Production and partial characterization of pili on non-O1 Vibrio cholerae. PMID- 2891774 TI - MR/K hemagglutination of Providencia stuartii correlates with adherence to catheters and with persistence in catheter-associated bacteriuria. AB - Providencia stuartii was the most prevalent bacterial species isolated, for one year, from weekly urine specimens from 51 long-term catheterized patients. Significantly more strains causing bacteriuric episodes of long duration expressed MR/K (mannose-resistant/Klebsiella-like) hemagglutination (74%) than did those causing episodes of short duration (26%; P = .004). Isolates expressing MR/K hemagglutinin bound in higher numbers to catheter material (P = .023) than did those not expressing this hemagglutinin. Significantly more strains causing bacteriuric episodes of short duration expressed the mannose-sensitive (MS) hemagglutinin (43%) than did those causing episodes of long duration (7%; P = .014). Isolates expressing MS hemagglutinin bound significantly more 125I-labeled Tamm-Horsfall protein (THP) than did isolates not expressing this hemagglutinin (P = .0001). Our results indicate that MR/K hemagglutinin plays an important role in the ability of P. stuartii to persist and suggest that MR/K adheres to the catheter. Conversely, MS hemagglutinin binds to THP and may prevent persistence of P. stuartii in the catheterized urinary tract. PMID- 2891775 TI - Lethal effects and cardiovascular effects of purified alpha- and theta-toxins from Clostridium perfringens. AB - Shock, a common and frequently fatal manifestation of gas gangrene caused by Clostridium perfringens, is probably mediated by extracellular toxins. Previous studies implicating alpha-toxin as the major lethal factor were frequently done with preparations contaminated with a second lethal factor, theta-toxin. We purified alpha- and theta-toxins from C. perfringens and demonstrated that both were lethal to mice. We investigated the effects of these purified toxins on cardiovascular function in intact rabbits; both toxins caused profound hypotension and bradycardia within 40 min. Reduced cardiac output preceded the development of hypotension and bradycardia. Purified alpha-toxin produced a dose dependent reduction in myocardial function in isolated rabbit atrial preparations. Purified theta-toxin did not directly inhibit myocardial function. Shock induced by alpha-toxin may be partly mediated by direct depression of myocardial function. theta-Toxin reduced cardiac output in intact animals but had no direct effects on isolated heart preparations at concentrations that induced shock in intact animals. These data suggest that theta-toxin-induced shock could be mediated by an endogenous myocardial depressant factor. PMID- 2891777 TI - Epidemiological aspects of a St. Louis encephalitis outbreak in Harris County, Texas, 1986. AB - An outbreak of St. Louis encephalitis (SLE) resulted in 28 cases of the disease in Harris County, Texas, in 1986. The cases occurred principally in Baytown, in eastern Harris County, but five cases were also recognized in Houston. The risk of illness increased sharply with age, and all five fatal cases were in persons greater than 55 y. Case-control methods were used for the first time to study factors associated with the risk of acquiring SLE. Risk was associated with residences poorly sealed against mosquitoes (non-air-conditioned residences and those with inadequate screens). The number of hours spent outdoors and in outdoor activities, except sitting immediately outside residences, were not associated with risk. Our observations suggest that exposure to vector mosquitoes may have occurred indoors. No host factors were significantly associated with risk of acquiring SLE, but more cases were cigarette smokers and had family histories of hypertension or cerebrovascular disease. PMID- 2891776 TI - Fragment length polymorphisms among independent isolates of Epstein-Barr virus from immunocompromised and normal hosts. AB - DNA restriction fragment length polymorphisms of Epstein-Barr virus (EBV) DNA were used as a molecular epidemiological tool to study multiple isolates of virus from the same and different individuals. We studied 35 EBV isolates: 19 from seven immunocompromised children and 16 from seven college students with mononucleosis. Analysis of the fragment length polymorphisms in this collection of isolates permitted several conclusions. Sites of polymorphism were most often encountered in regions with repetitive DNA. Epidemiologically unrelated patients harbored viruses that could be readily distinguished; by contrast, two infants and their mothers harbored similar viruses. Isolates from different sites in the same patient were similar. Variations between different clinical isolates of EBV mimic those found between different laboratory strains of the virus. Fragment length polymorphisms thus provide a useful marker for studying transmission and pathogenesis of EBV infections. PMID- 2891779 TI - Infectious diarrhea due to Clostridium perfringens. PMID- 2891778 TI - Hemorrhagic complications and other clinical findings in nephropathia epidemica in Sweden: a study of 355 serologically verified cases. PMID- 2891780 TI - Cell surface antigens of human melanocytes and melanoma. Expression of adenosine deaminase binding protein is extinguished with melanocyte transformation. AB - It has been proposed that the pathogenesis of melanoma proceeds through multiple stages, ranging from benign proliferation of melanocytic cells to acquisition of the capacity to invade tissues and metastasize. During investigations of cell surface antigens expressed by melanocytes and melanoma, we identified an antigen system that was expressed by cultured normal melanocytes but not by melanoma cell lines. mAbs against this antigen detected a 120-kD cell surface glycoprotein on melanocytes. This molecule had been identified previously as the binding protein for adenosine deaminase (ADAbp). ADAbp was expressed by 51 melanocyte cell lines derived from normal fetal, newborn, and adult skin and adult choroid, but not by 102 melanoma cell lines derived from primary and metastatic lesions. Studies with radiolabeled bovine adenosine deaminase, confirmed that melanocytes expressed binding sites for adenosine deaminase, but no binding sites were detected on cultured melanoma cells. Further studies showed that ADAbp+ melanocytes became ADAbp- upon malignant transformation in vitro. Immunohistochemical studies on a panel of frozen tissues demonstrated reactivity of anti-ADAbp mAbs with epidermal melanocytes and benign junctional nevi, but not with potentially premalignant dysplastic nevi or primary/metastatic melanoma lesions. These studies demonstrate that ADAbp expression is lost with malignant transformation of melanocytes, presumably at an early stage in the transformation process. PMID- 2891781 TI - Characterization of a 280-kD protein restricted to the coated pits of the renal brush border and the epithelial cells of the yolk sac. Teratogenic effect of the specific monoclonal antibodies. AB - Intermicrovillar areas and apical vesicles characterized by an extensive clathrin coat can be identified in some epithelial cell types. We describe a 280-kD protein, characteristic of these areas in the proximal tubule brush border and epithelial cells of the visceral yolk sac. When injected to 9-d pregnant rats, mAbs to the 280-kD protein regularly induced fetal resorption and/or malformations. Antibodies to a 330-kD protein that is also coated-pit-restricted had no effect. Our observations point to a key function for p280 and suggest that immunity to specific constituents of the receptor-mediated endocytotic system may be involved in the induction of fetal abnormalities. PMID- 2891782 TI - Salivary testosterone: its application in the follow-up of hypo- and hyper androgenic states. PMID- 2891783 TI - D-aspartate uptake and release in the guinea pig spinal cord after partial ablation of the cerebral cortex. AB - This study attempts to determine if L-glutamate and L-aspartate may be transmitters of the guinea pig corticospinal tract. Unilateral ablations were made of the frontal and parietal neocortex which destroyed most of the motor and somatosensory areas in the right cerebral hemisphere. In lesioned animals, transverse sections of the cervical enlargement of the spinal cord (segments C6- T1) were stained to reveal degenerating fibers. Degeneration of axons first appeared 4 days after surgery, reached a maximum on the seventh day, and began to wane by the ninth day. The most prominent loss of axons appeared deep in the dorsal funiculus and in laminae IV-IX of the gray matter contralateral to the cortical lesion. Ipsilaterally, there was very sparse degeneration of fibers in the dorsal and ventral funiculi and in the spinal gray matter. The uptake and release of D-[3H]aspartate, a putative nonmetabolizable marker for L-glutamate and L-aspartate, were measured in dissected quadrants of the cervical enlargement taken from intact and lesioned animals. The uptake and the electrically evoked, Ca2+-dependent release of D-[3H]aspartate were depressed by 29-35% at 4 and 7 days after surgery, but only in tissue that was contralateral to the cortical ablation. The lesion had no effect on the uptake and release of exogenous gamma [14C]aminobutyric acid, which were measured as indices of the postlesion integrity of neurons in the spinal gray matter. These findings suggest that the synaptic endings of corticospinal fibers probably mediate the uptake and release of D-[3H]aspartate and, therefore, may use L-glutamate and/or L-aspartate as a transmitter. PMID- 2891784 TI - Tyrosine hydroxylase activity in caudate nucleus from Parkinson's disease: effects of iron and phosphorylating agents. AB - Tyrosine hydroxylase (TH) activity of human postmortem brain tissues from controls and patients with Parkinson's disease (PD) was examined in the presence of Fe2+ and phosphorylation agents, such as cyclic AMP, exogenous protein kinase, calcium plus calmodulin (Ca2+-CaM), and ATP. TH activity from parkinsonian tissue was increased by 48% with statistical significance in the presence of exogenous protein kinase. Cyclic AMP alone had no effect, whereas Ca2+-CaM increased the activity by only 10%. The presence of acetylcholine resulted in a slight decrease in enzyme activity. Human TH was stimulated 13.17-fold in the presence of 1 mM Fe2+. For iron dependence, no significant differences could be shown for the Km values of TH in striata of PD, while the activity of TH was half of that of controls. Here stimulation with 1 mM Fe2+ raised the activity of TH 11-fold. Stimulation of rat, gerbil, pig, and human caudate nucleus TH with Fe2+ shows remarkable species differences. In particular, the sensitivity of human TH to stimulating processes is noteworthy. H2O2 decreases TH activity only at high concentrations. Species differences are noted for the combined incubation of Fe2+ and H2O2. In the gerbil caudate nucleus, H2O2 does not prevent the stimulating properties of Fe2+, while the pig shows a dose-dependent decline of TH activity. In conclusion, there are no significant changes in the stimulating properties of human caudate nucleus TH activity with Fe2+ in PD, while such differences are noted by using exogenous protein kinase. Furthermore, experimental evidence shows that TH activity declines at high concentrations of H2O2 only. Potentiation of this effect by Fe2+ seems to be species-dependent. PMID- 2891785 TI - Changes in the relative amounts of aspartate and glutamate released and retained in hippocampal slices during stimulation. AB - It has been found previously that the ratio of aspartate to glutamate released and retained by brain slices reversibly changes with changing glucose concentrations in the medium. To find out whether increased neuronal activity also results in changes in the ratio of aspartate to glutamate, in this study electrical-field stimulation was applied for 10 min to hippocampal slices in the presence of 0.2-5 mM glucose. In 5 mM glucose, the ratio of aspartate to glutamate released did not change during stimulation, but the amount of aspartate retained at the end of stimulation was reduced. In contrast, in 1 mM or less glucose, the ratio of aspartate to glutamate released increased progressively and the rate of increase was inversely proportional to the glucose content of the medium. The evoked release of aspartate and glutamate both in low and high glucose was nearly suppressed in low (0.1 mM) Ca2+ or by tetrodotoxin. In low glucose, the ratio of aspartate to glutamate contained in the slices also increased as a result of stimulation. This increase was reduced only a little in low Ca2+, but was nearly eliminated by tetrodotoxin. Results suggest that increased neuronal activity causes a shift in the ratio of aspartate to glutamate released in the presence of glucose concentrations similar to those found in the brain in normoglycemic rats. This shift, due to an increased energy demand, probably originates from terminals which release aspartate and glutamate in different proportions. PMID- 2891786 TI - Brain coated vesicle destabilization and phosphorylation of coat proteins. AB - Two basic polypeptides, bee venom melittin and poly-L-lysine, induced concentration-dependent destabilization of bovine brain coated vesicles. Ultrastructurally the changes observed were aggregation of clathrin coats and segregation of the vesicle membrane, concomitant with the appearance of elongated cisternae of various sizes. Changes in coated vesicle morphology induced by melittin and poly-L-lysine were concurrent with stimulation of phosphate incorporation in proteins of the coat lattice: Mr 33,000 and 100,000. Melittin stimulated phosphorylation was Ca2+ sensitive and inhibited by EGTA. The initiation of vesicle membrane segregation by melittin, followed by fusion and formation of elongated membrane cisternae, paralleled an increase of endogenous phospholipase A2 activity. The data suggest that a correlation exists between the state of assembly of the coat proteins on coated vesicles and protein phosphorylation. PMID- 2891787 TI - Carbonic anhydrase immunostaining in astrocytes in the rat cerebral cortex. AB - Carbonic anhydrase is known to occur in the choroid plexus, oligodendrocytes, and myelin, and to be virtually absent from neurons, in the mammalian CNS; however, there is significant controversy whether it is also present in astrocytes. When brain sections from adult rats were stained for simultaneous immunofluorescence of carbonic anhydrase and the astrocyte marker glutamine synthetase, both antigens were detected in the same glial cells in the cortical gray matter, whereas the oligodendrocytes and myelinated fibers in and adjacent to the white matter showed immunofluorescence only for carbonic anhydrase. Some glial cells in the gray matter also showed double immunofluorescence for carbonic anhydrase and glial fibrillary acidic protein. These results indicate that there is carbonic anhydrase in some astrocytes in the mammalian CNS. PMID- 2891788 TI - Characterization and localization of glutathione-S-transferases in rat brain and binding of hormones, neurotransmitters, and drugs. AB - Rat brain glutathione-S-transferases are rich in Yb type subunits with major RNA transcripts coding for a relatively uncommon Yb3 form. The Yb-containing isoenzymes of brain cytosol bind glucocorticoids and are covalently labeled with dexamethasone 21-methanesulfonate. Certain neurotransmitters, hormones, and drugs, such as serotonin, dopamine, glucocorticoids, thyroxine, apomorphine, and benzodiazepine derivatives, are effective inhibitors of brain glutathione transferase activity. Immunocytochemical studies show that Yb forms are localized in ependymal cells, subventricular zone cells, astrocytes, tanycytes, and astrocyte foot processes on blood vessels, but Yb was not detected in oligodendrocytes or neurons. Based on their localization and binding properties, brain glutathione-S-transferases have the potential to function in intracellular binding of a variety of compounds and thereby govern their uptake and release in brain, transport to neurons, as well as in their detoxification. PMID- 2891789 TI - Mutual antagonism of kappa-opiate and alpha 2-adrenoceptor agonist effects on intrasynaptosomal free [Ca2+]i. AB - Synaptosomes prepared from rat cerebral cortices on Percoll discontinuous density gradients were loaded with the fluorescent EGTA analogue Quin 2 to allow measurement of intracellular free [Ca2+]i. When either kappa-opiate or alpha 2 adrenoceptor agonists were incubated with the synaptosomes, there was a highly significant (p less than 0.004, p less than 2.7 X 10(-6), respectively) reduction in intrasynaptosomal free [Ca2+]i relative to controls. As these synaptosomes are not depolarised, the data suggest that both alpha 2-adrenoceptor agonists and kappa-opiate agonists inhibit neurotransmitter release, decreasing the availability of intraneuronal [Ca2+]i rather than altering Ca2+ entry. However, when these two agonists were coincubated, there was a complete abolition of the effects of either agonist; in fact, there was an apparent increase in the intrasynaptosomal free [Ca2+]i. Neither morphine nor [D-Ala2-D-Leu5]enkephalin, mu and delta opiate agonists respectively, had any significant effect on intrasynaptosomal free [Ca2+]i. These results show that the individual effects of clonidine and dynorphin A1-13 are in keeping with the role of these substances at autoreceptors controlling neurotransmitter release. The mutual antagonism of their effects on [Ca2+]i is more difficult to explain but it may be a mechanism that prevents the occurrence of excessive inhibition of neuronal systems. PMID- 2891790 TI - Glutamate transport in large muscle fibres of Balanus nubilus. AB - The uptake of glutamate and other acidic amino acids into barnacle single muscle fibres has been characterized. The uptake of glutamate consists of two components, one Na-independent and one Na-dependent. The Na-dependent uptake is saturable (half-maximal at 250 microM external glutamate) and is inhibited by a variety of analogues of which L-cysteate and D- and L-aspartate are the most potent. These amino acids are also transported into the muscle in a Na-dependent manner. The excitatory agonists kainate, quisqualate, and N-methyl-D-aspartate do not inhibit or affect uptake in any way. Progressive replacement of external Na by choline reduces uptake with very little effect on the apparent affinity for glutamate, suggesting that Na and glutamate bind to the transporter independently. The kinetics of activation are consistent with a requirement for at least two Na ions. Na activation of glutamate uptake can be inhibited by guanidinium with kinetics that are consistent with competitive inhibition at the Na binding site. Studies on the efflux of L-glutamate and other analogues have shown that efflux rates are only slightly increased by the removal of Na and do not seem to be affected in any clear manner by external levels of acidic amino acids. PMID- 2891791 TI - Potentiation by kainate of excitatory amino acid release in striatum: complementary in vivo and in vitro experiments. AB - The effect of kainate on extracellular levels of amino acids in corpus striatum was investigated in vitro and in vivo, to elucidate the mechanism underlying its neurotoxicity. Kainate increased extracellular glutamate and aspartate in both striatal slices in vitro and intact striatum in vivo, as previously reported. Both in vitro and in vivo, DL-threo-3-hydroxyaspartate increased extracellular glutamate and aspartate levels (to between 150 and 200% of basal), and also enhanced their kainate-evoked release. The action of kainate in vivo was reduced by prior frontal decortication, whereas in vitro the kainate-evoked responses were only slightly reduced by tetrodotoxin, and remained above control values. These results confirm that kainate increases extracellular glutamate and aspartate, and provide evidence that this is due to synaptic release evoked by an action on receptors on glutamatergic neurone terminals. These findings may be relevant to the understanding of epilepsy. PMID- 2891792 TI - Effects of dorsal bilateral rhizotomy treatment on transmitter systems in the spinal cord of normal and spastic dogs. AB - The high-affinity uptakes of [3H]serotonin, [3H]-glutamate, and gamma [3H]aminobutyric acid were studied using a myelin-free crude synaptosomal fraction prepared from the spinal cords of normal dogs and spastic dogs following sham treatment or dorsal bilateral rhizotomy surgery. Compared to sham-operated controls, rhizotomy surgery of normal dogs produced, after 1 week, a 30% reduction in the Vmax value of [3H]glutamate, but did not alter the uptake of gamma-[3H]aminobutyric acid. This treatment also produced a 60% decrease in the Vmax value of [3H]serotonin. Comparison of the effect of rhizotomy surgery on normal and spastic dogs revealed that the spastic group had 60% higher Vmax values for uptakes of [3H]glutamate and gamma-[3H]aminobutyric acid. Comparison of sham-operated spastic dogs and rhizotomy-treated spastic animals showed that there was a 25% decrease in the uptake of both amino acids in the rhizotomy treated spastic group. Overall, the data (a) support the hypothesis that glutamate is the neurotransmitter from some of the primary afferents, and (b) suggest that sprouting of interneuronal amino acid transmitter systems may occur in the spinal cords of spastic dogs. PMID- 2891793 TI - Management of subdural empyema: a series of 24 cases. AB - Twenty four cases of subdural empyema are reviewed. The overall mortality was 17%, 18 patients were managed by burr hole and five by craniotomy or craniectomy. Antibiotic therapy was commenced once pus had been evacuated. Infection of the paranasal and mastoid sinuses was the commonest aetiological factor. Aspiration of pus through burr holes is the recommended surgical procedure with low mortality and morbidity, when combined with early diagnosis and aggressive chemotherapy. PMID- 2891794 TI - The inflammatory process in polymyositis: monoclonal antibody analysis of muscle and peripheral blood immunoregulatory lymphocytes. AB - An analysis was made of the lymphocyte subpopulations in the muscle lesions and the peripheral blood of 25 patients with inflammatory myopathy, in the acute or chronic phase of the disease. Percentages of activated T lymphocytes (65% +/- 3.4), both helper and suppressor/cytotoxic, macrophages (25% +/- 3.2) and B cells (11% +/- 0.9) in the tissues were similar at all stages of the illness; T cells were, however, more common in acute polymyositis than in acute dermatomyositis, where B cells were significantly increased. A loss of circulating OKT8-positive lymphocytes in the peripheral blood was demonstrated, supporting other evidence of disturbed immunoregulation. It was concluded that the attack on muscle fibres is mediated by T cells, macrophages, and B cells, with the first two playing the major roles. PMID- 2891795 TI - Brain somatostatin concentrations do not decrease in progressive supranuclear palsy. AB - The concentrations of somatostatin and choline acetyl transferase (CAT) were measured in nine brains from patients with progressive supranuclear palsy (PSP) and compared with those obtained from 19 matched control brains. In PSP, CAT activity was reduced in the caudate nucleus and limbic areas (amygdala, hippocampus and cingulate cortex) but was not different from controls in neocortical areas (frontal and temporal). Somatostatin concentrations were not different from controls in any region tested. In contrast to Alzheimer's disease and Parkinson's disease, intellectual deterioration in PSP is not associated with a deficit in neocortical somatostatin and CAT levels. PMID- 2891796 TI - Distribution and morphology of dopaminergic amacrine cells in the retina of the turtle (Pseudemys scripta elegans). AB - A light microscopical study of the cell types that stain by immunohistochemistry for the synthesizing enzyme for dopamine, tyrosine hydroxylase, has been performed on the retina of the turtle Pseudemys scripta elegans. The immunostain can be localized to a single morphological type of amacrine cell. The cells are like A28 cells of a Golgi classification. They have medium sized dendritic fields that range in diameter from 200 to 700 micron with eccentricity from the visual streak. The amacrines have a tri-stratified dendritic tree with tiers of fine, curved dendrites ramifying in strata S1, lower S2 and the S4/5 border of the inner plexiform layer. We, like others, can find no good evidence that these cells are interplexiform cells. The dopaminergic amacrine cells have a low frequency (approximately 1300-1500 total cells in 130 mm2 retina), with their highest density occurring in the visual streak (60 cells per mm2). The density profiles fall in elliptical isodensity rings from the visual streak towards the peripheral retina. At all points on the retina the dendritic fields maintain a constant coverage factor independent of eccentricity. A comparison of the dopaminergic amacrine cells in the turtle and other vertebrate retinae is made. PMID- 2891797 TI - Chemotherapeutic results and prognostic factors of patients with advanced non Hodgkin's lymphoma treated with VEPA or VEPA-M. AB - One hundred sixty-three patients with advanced non-Hodgkin's lymphoma including adult T cell leukemia/lymphoma (ATL) were treated from 1981 to 1983 with VEPA (vincristine, cyclophosphamide, prednisolone, and doxorubicin) or VEPA-M (VEPA plus methotrexate) in randomized fashion after stratification by surface marker. The complete response (CR) rate and the 4-year survival rate of patients treated with VEPA-M was 62.2% and 36.9%, respectively, while for those treated with VEPA the rates were 51.9% and 26.6, respectively. The difference was not statistically significant, but pretreatment characteristics predictive for response and survival were interesting. Three factors, leukemic change, poor performance status (PS), and T cell marker, were negatively associated with both CR and survival rates, and high-grade pathology was adversely associated with survival rate in a multivariate analysis. These prognostic factors are somewhat different from those in Western lymphomas. This may be reflection of major differences in patients' characteristics between Japanese and Western lymphomas: in this study, there was a high incidence of T cell lymphoma/leukemia (50%) including ATL (33%), leukemic manifestation (34%), poor PS (34%), and a low incidence of follicular lymphoma (9%). The statistically significant three factors for both CR and survival rates were used to construct a model containing eight categories of patients at increasing risk for poor response and shortened survival. These categories were divided into four groups, with respective CR and 4-year survival rates of 91% and 73%, 67% and 35%, 27% and 7%, and 10% and 5%. Ninety-three patients in whom CR was induced by VEPA or VEPA-M therapy were evaluated for prognostic factors predictive for disease-free survival. A shorter period (less than 28 days) required to achieve CR, a clinical diagnosis of ATL, and a lower hemoglobin level were found to affect disease-free survival adversely. These results have important implications for both the design of prospective randomized therapeutic trials and the determination of optimal therapy for individual patients. PMID- 2891798 TI - The benefit of adjuvant treatment for resected locally advanced non-small-cell lung cancer. The Lung Cancer Study Group. AB - The purpose of this trial was to investigate the impact of systemic combination chemotherapy on survival and recurrence patterns in incompletely resected non small-cell lung cancer. Incomplete resection was defined as presence of residual tumor in the resection margin or by presence of metastasis in the highest paratracheal lymph node sampled during protocol-directed surgical staging of the mediastinum. One hundred seventy-two patients were randomized to receive either postoperative radiotherapy (RT) alone or postoperative RT plus chemotherapy with CAP (Cytoxan [cyclophosphamide; Bristol Myers, Evansville, IN], Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH], and Platinol [cisplatin; Bristol Myers]) for 6 months. One hundred sixty-four patients were eligible for analysis at a mean time since randomization of 3.7 years. The chemotherapy arm showed significantly longer recurrence-free survival (two-sided Mantel-Haenszel log rank test, P = .004). This difference holds true for nonsquamous patients (P = .01), and approaches significance for squamous patients as well (P = .08). There was a 14% difference in survival rate favoring the chemotherapy arm 1 year after randomization. Analysis of sites of recurrence showed a significant decrease in distant metastases in the chemotherapy arm. Median survival for the entire group was approximately 17 months, and 35% are alive 2 years after resection. Toxicity of treatment consisted of esophagitis (mild-moderate by Eastern Cooperative Oncology Group [ECOG] criteria) and predictable hematologic, gastrointestinal (GI), and skin toxicity expected from CAP. PMID- 2891799 TI - The neostriatal mosaic: II. Patch- and matrix-directed mesostriatal dopaminergic and non-dopaminergic systems. AB - Mesostriatal projections, which arise from dopaminergic and non-dopaminergic neurons in the ventral tegmental area, substantia nigra, and retrorubral area, are compartmentally organized in the striatum. Anterograde axonal tract tracing with Phaseolus vulgaris-leucoagglutinin (PHA-L), combined with immunohistochemical localization of tyrosine hydroxylase (TH) and autoradiographic localization of mu-opiate receptor binding sites, shows that midbrain projections to the striatum are distributed to either the mu-opiate receptor-rich "patch" or the receptor-poor "matrix" striatal compartments. Three morphologically distinct mesostriatal afferent fiber types are labeled. The first type, type A, forms a plexus of relatively thin (0.1-0.4 micron), smooth fibers with small varicosities (0.3-0.6 micron). A second type, type B, is similar to the first in forming a plexus of fibers, but is slightly thicker (0.2-0.6 micron), with more frequent varicosities (0.4-1.0 micron) that give this fiber type a crinkled appearance. The third type, type C, constitutes a minority of striatal afferents and is characterized by its large caliber (0.4-0.7 micron) with large bulbous varicosities (1.2-2.0 micron). Projections of the ventral tegmental area (A10 cell group) are primarily dopaminergic type A fibers directed to the matrix of the ventromedial striatum, including the nucleus accumbens. The retrorubral area (A8 cell group) also provides predominantly dopaminergic type A fibers to the striatal matrix, but these are distributed dorsally. The substantia nigra contains a mixed population of neurons that project to the striatum. Some, located in the dorsal tier of the pars compacta (dorsal A9 cell group), provide dopaminergic type A fibers to the striatal matrix. Others, in the ventral tier of the pars compacta (ventral A9 cell group) and in the ventral tier of the pars reticulata (displaced A9 cells), provide dopaminergic type B fibers to the striatal patches. An additional set of substantia nigra neurons that are non dopaminergic is the source of type C fibers to the striatal matrix. Thus, distinct dorsal and ventral sets of midbrain dopaminergic neurons project, respectively, to striatal matrix and patches, and there is a non-dopaminergic mesostriatal projection to the matrix. PMID- 2891800 TI - The neostriatal mosaic: III. Biochemical and developmental dissociation of patch matrix mesostriatal systems. AB - In the previous paper (Gerfen et al., 1987) mesostriatal dopaminergic neurons were shown to be subdivided into dorsal and ventral tiers that project to the striatal matrix and patch compartments, respectively. The present study provides experimental evidence that these patch-matrix mesostriatal dopaminergic systems are biochemically and developmentally distinct. A 28 kDa calcium-binding protein (CaBP, or calbindin-D28 kDa) is expressed in dorsal tier mesostriatal dopaminergic neurons. The distribution of such neurons, located in the ventral tegmental area, dorsal tier of the substantia nigra pars compacta, and retrorubral area, matches that of dopaminergic neurons that project to the striatal matrix. Dopaminergic neurons that do not express CaBP--those in the ventral tier of the pars compacta and in the pars reticulata--are distributed in a pattern that matches the origin of the dopaminergic projection to the striatal patches. During development, dopaminergic afferents to the striatal patch compartment are in place prior to the development of those to the matrix. Injections of the neurotoxin 6-hydroxydopamine (6-OHDA) into the striatum of newborn rats result in a selective and long-lasting depletion of dopaminergic afferents in the striatal patches. The later-developing matrix projection is relatively spared by such lesions. The distribution of surviving dopaminergic neurons, labeled with tyrosine hydroxylase (TH) immunoreactivity, matches the pattern of dorsal tier neurons previously shown to provide inputs to the matrix. Surviving neurons also express CaBP immunoreactivity and have dendrites that spread mediolaterally, in the plane of the pars compacta. On the other hand, those neurons that project to the patches are selectively lesioned by the neonatal 6-OHDA striatal injections, do not express CaBP, and have dendrites that are directed ventrally into the pars reticulata. PMID- 2891801 TI - Catecholaminergic horizontal and amacrine cells in the ferret retina. AB - Enzymes involved in the synthesis of catecholamines were detected in amacrine and what appeared to be a specific class of horizontal cells in the ferret retina. Antisera directed against the enzymes tyrosine hydroxylase (TH), which converts tyrosine to DOPA, and phenylethanolamine N-methyl-transferase (PNMT), which converts norepinephrine to epinephrine, were used with conventional immunohistochemical techniques. A population of perikarya located at the outer margin of the inner nuclear layer (INL) exhibited TH-like immunoreactivity. The cell bodies were 9-12 micron in diameter and gave rise to stout dendrites that tapered rapidly after emergence from the somata. The processes formed a planar array in the inner half of the outer plexiform layer (OPL) slightly external to the cells of origin. We could not detect any inwardly directed processes. A population of PNMT-positive cells was also observed in the outer tier of cells in the INL. These cells were very similar to those exhibiting TH immunoreactivity. An apparent difference between the 2 populations was that there were areas of intense, somewhat punctate PNMT immunoreactivity in the outer OPL. These were not observed in the TH-stained sections. Examination of horizontal sections showed that each TH-positive cell body gave rise to 4-5 major dendrites that branched to form a roughly circular dendritic field. In the periphery of the retina, an individual cell's dendrites encompassed an area up to 170 micron in diameter. The dendritic fields of cells near the center of the retina were substantially smaller.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891802 TI - Dopaminergic innervation of A II amacrine cells in mammalian retina. AB - Dopaminergic amacrine cells were stained in cat, rat, and rabbit retina using an antibody against tyrosine hydroxylase (TH). Following intraocular injection of DAPI (4,6,diamidino-2-phenylindole), subsequent retinal whole-mount preparations revealed that the dopaminergic fiber plexus formed rings around amacrine cell bodies. Intracellular injection of Lucifer yellow (LY) into A II amacrine cells confirmed that this rod-related, bistratified interneuron has its cell body within the dopaminergic rings. Using a photooxidation process, LY was transformed into an electron-dense reaction product, enabling ultrastructural examination of LY-injected A II amacrine cells. In retinae counterstained with an antibody against TH, it was possible to show synapses from TH-positive fibers onto these cells. The dopaminergic plexus was further investigated by injecting single dopaminergic cells with LY and thus revealing their branching pattern. The present results emphasize the role of dopamine in modulating the rod pathway in mammalian retina. PMID- 2891804 TI - AIDS and atoms. PMID- 2891803 TI - Benefits of treatment of mild to moderate hypertension. PMID- 2891805 TI - Influence of volume of fluid on effectiveness of ipecac. PMID- 2891806 TI - Effect of short-term somatostatin and long-term triiodothyronine administration in a child with nontumorous inappropriate thyrotropin secretion. PMID- 2891807 TI - Modification of somatostatin content and binding in jejunum from celiac children. AB - The concentration of somatostatin was studied in controls as well as in plasma and jejunal mucosa from celiac children with and without jejunal villous atrophy. The binding of somatostatin to cytosolic fraction, isolated from jejunal mucosa from celiac patients and controls, was also investigated. Fasting plasma somatostatin concentrations were not significantly different among the various groups studied. However, the jejunal somatostatin content was significantly higher in the group of celiac children with subtotal villous atrophy as compared to control group and celiac children with normal villous architecture. The binding of somatostatin to cytosol of jejunal mucosa was significantly decreased in the group of celiac children with subtotal villous atrophy. The present results suggest that somatostatin may be involved in the pathophysiological processes of celiac disease. PMID- 2891810 TI - Characterization of N-CBz-glycyl-glycyl-arginyl peptidase and glycyl-prolyl peptidase of Bacteroides gingivalis. PMID- 2891808 TI - Watery diarrhea, hypokalemia, achlorhydria syndrome in an infant: effect of the long-acting somatostatin analogue SMS 201-995 on the disease and linear growth. AB - An 8-week-old infant presented with vomiting and failure to thrive due to small bowel obstruction caused by a diffusely enlarged pancreas. Surgical bypass of the obstruction was followed by secretory diarrhea, hypokalemia, and dehydration. Plasma vasoactive intestinal peptide (VIP) (823pg/ml), pancreatic polypeptide (4,500 pg/ml), and neurotensin (680 pg/ml) concentrations were markedly elevated. No neoplastic process was identified. Therapy with the long-acting somatostatin analogue SMS 201-995 was followed by decline in VIP concentrations (900 to 200 300 pg/ml), decrease in stool frequency, and normalization of serum electrolytes. During 12 months of somatostatin analogue therapy, length and weight progressed along the 3rd percentile on the Tanner growth chart. PMID- 2891809 TI - Marked basal gastric acid hypersecretion and peptic ulcer disease: medical management with a combination H2-histamine receptor antagonist and anticholinergic. AB - Three children with peptic ulcer disease had recurrent symptoms unresponsive to cimetidine or ranitidine therapy alone. Acid secretory studies showed a marked basal acid hypersecretion, which was atropine-sensitive in two of three patients and was best suppressed by ranitidine in combination with an anticholinergic drug. Marked reduction in acid output following intravenous atropine suggested that the hypersecretion was under vagal, muscarinic control. However, in one patient, large doses of the selective m1-muscarinic antagonist pirenzepine were ineffective in suppressing basal acid hypersecretion. Given the efficacy and safety of drug therapy used in these children over a 3-year period, we conclude that medical management is an effective alternative to surgery for pediatric patients with refractory or recurrent peptic ulcer disease. PMID- 2891811 TI - A comparison of the inhibitory effects of roxatidine acetate hydrochloride and cimetidine on cytochrome P-450-mediated drug-metabolism in mouse hepatic microsomes and in man in vivo. AB - The inhibitory effects of roxatidine acetate hydrochloride (ROX), a new H2 receptor antagonist, on the oxidative drug-metabolizing enzyme system in mouse hepatic microsomes and in man in vivo were compared with those of cimetidine (CIM). CIM markedly inhibited testosterone 6 beta-, 7 alpha- and 16 alpha hydroxylase, aminopyrine N-demethylase and aniline hydroxylase activities in mouse hepatic microsomes with inhibition constants (Ki) of 0.2-3.49 mM. ROX exhibited much weaker inhibitory effects on each enzyme activity with 12 to 100 fold higher values of Ki than those of CIM. CIM gave type II difference spectra with dissociation constants (Ks) of 10.4 and 111 microM while ROX gave reverse type I difference spectra with Ks of 55.6 microM. The ratio of 6 beta hydroxycortisol (6 beta-OHF) to 17-hydroxy corticosteroids (17-OHCS) in urine, used as an indicator of oxidative drug-metabolizing capacity in man, was decreased by 25-35% of the original level on 1-3 d after oral treatment with 800 mg/d of CIM. The ratio was not significantly changed during oral treatment with 150 mg/d of ROX. These results indicate that ROX exhibits a lower affinity for cytochrome P-450 and a lower inhibitory potency on the drug-metabolizing enzymes in hepatic microsomes than does CIM. PMID- 2891812 TI - British pharmaceutical conference 1987. Science proceedings. 124th meeting, Manchester, September 14-17, 1987. Abstracts. PMID- 2891813 TI - Enhancement of the dissolution rate of a poorly water-soluble drug (tolbutamide) by a spray-drying solvent deposition method and disintegrants. AB - The dissolution rate of a poorly water-soluble drug, tolbutamide, was improved by spray-drying a diluted ammonia solution of the drug containing either a low substituted hydroxypropylcellulose (L-HPC) or partly pregelatinized corn starch (PCS) as disintegrants. With L-HPC the resultant particles were agglomerates of disintegrant with drug on the surface and within the particles, while particles formed with PCS were composed of a single core of PCS on which the drug was deposited. The deposited drug crystals were very fine because the rapid solvent evaporation restricted crystal growth. The spray-dried particles prepared with PCS had a structure similar to that of an ordered mix. The drug dissolution rate from the spray-dried particles was more rapid than that of the powdered drug alone or with disintegrant and could be attributed to separation of the layer of fine drug crystals from the surface of the particles by swelling of disintegrant. PCS enhanced the drug dissolution rate compared with systems using corn starch. The dissolution rate also depended on the drug content of the particles which was higher than that in ordered mixtures or conventional solvent deposition systems. This system described also had the advantage of avoiding the use of organic solvents. PMID- 2891814 TI - A thermodynamic analysis of the Collander equation and establishment of a reference solvent for use in drug partitioning studies. AB - A thermodynamic analysis of the Collander equation, ln PI = a + b ln PII (I and II refer to two different partitioning systems with partition coefficients PI and PII, respectively), is given and applied to three forms of correlation. The intercept, a, is shown to have no general fundamental significance whereas the slope, b is shown to reflect differences in non-aqueous solvent properties; b is also shown to be of use in scaling solvent behaviour to select solvents which closely represent biological membrane properties for use in partitioning studies. Laboratory and literature data are subjected to the analysis. PMID- 2891815 TI - Haem arginate: a new stable haem compound. AB - Intravenous administration of haem in acute hepatic porphyrias inhibits the induction of delta-aminolaevulinic acid synthase, reduces the formation of potentially harmful metabolites of porphyrin synthesis and corrects the haem deficiency. Typically, haem therapy has been given in the form of haematin--haem dissolved in alkali. Such haematin solutions are, however, extremely unstable. Thus, the rapid decomposition of this therapeutic agent may have been responsible for the ineffectiveness of treatment in some clinical states and adverse reactions may have been caused by haematin degradation products. There is, therefore, a need for a stable, effective and well-tolerated haem preparation. We have prepared certain highly soluble haem compounds of which haem arginate has proved to be the most promising. Pure haemin was isolated from HIV and hepatitis B negative human blood. The haem derivatives prepared were screened as substrates for haem oxygenase. Haem arginate and haem lysinate were found to be as good substrates as methaemalbumin. Stock solutions of haem arginate were stable for 2 years at +6 degrees C. After dilution with sterile isotonic saline the haem arginate infusion was clearly more stable than haematin solutions made in the laboratory or prepared by dissolving commercial lyophilized haematin. The antiporphyrogenic effect of haem arginate (even after storage for two years) in 2 allyl-2-isopropylacetamide-induced experimental porphyria of rats was equal to that of freshly prepared haematin. The acute oral toxicity of haem arginate was low compared with the parenterally administered drug, indicating poor oral bioavailability. The acute toxic effects after high intravenous or intraperitoneal doses were directed to the liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891816 TI - Crystallographic, theoretical and molecular modelling studies on the conformations of the salicylamide, raclopride, a selective dopamine-D2 antagonist. AB - The structure of the potent dopamine-D2 antagonist, raclopride, (S)-3,5-dichloro N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-methoxysalicylamid e (+)-tartrate, has been determined by X-ray crystallography. The benzamide moiety of raclopride is planar in accordance with other salicylamides (FLA 797 and eticlopride). The planar conformation is stabilized by two intramolecular hydrogen bonds, i.e. one between the amide hydrogen and the methoxy group and one between the phenol hydrogen and the carbonyl group. The side-chain of raclopride has an extended conformation in contrast to the solid state conformations of FLA 797 and eticlopride. The side chain conformations were studied by rigid rotations followed by MM2PI relaxations of the eight local minima found. Small energy differences (less than 4.0 kcal mol 1) exist between the various extended and folded conformations. Based on modelling studies with piquindone as template, it is suggested that the salicylamides with N-ethyl-2-pyrrolidinylmethyl side-chains interact with the dopamine-D2 receptor in a folded or a half-folded conformation. PMID- 2891817 TI - Effect of 8-phenyltheophylline, enprofylline and hydrochlorothiazide on glycerol induced acute renal failure in the rat. AB - The adenosine antagonist 8-phenyltheophylline (8-PT) is a diuretic in normal rats and can ameliorate glycerol-induced acute renal failure (ARF) in this species. To define which action of 8-PT is important in its salutary effect in ARF, we have compared its effects with those of enprofylline (a xanthine with little affinity for adenosine receptors) and with those of the tubular diuretic hydrochlorothiazide. In one series of experiments, groups of rats with ARF of 24 h duration were given a single dose of drug or vehicle. Only 8-PT enhanced urine volume when compared with the vehicle-treated group. In a second set of experiments, groups of glycerol-injected rats received drug or vehicle treatment (i.p.) twice daily for 2 days. Rats which received a course of 8-PT treatment had significantly lower plasma urea and creatinine concentrations, a higher glomerular filtration rate, a lower kidney weight and improved kidney morphology when compared with vehicle-treated rats. The only beneficial effect noted after enprofylline treatment was an improved kidney morphology. Hydrochlorothiazide treatment compared with vehicle treatment did not ameliorate any index of renal function but resulted in significant elevations in plasma urea and creatinine levels. The inability of enprofylline or hydrochlorothiazide to mimic the effects of 8-PT in ARF indicate that the effects of 8-PT are probably associated with adenosine receptor blockade and not with a tubular diuretic action. PMID- 2891818 TI - L-dopa esters as potential prodrugs: effect on brain concentration of dopamine metabolites in reserpinized mice. AB - The intraperitoneal administration of L-dopa and a series of ester prodrugs of L dopa to reserpinized mice produced elevations of striatal and tuberculum olfactorium homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels. Differences in the pattern of change produced by individual drugs, compared with L-dopa, were observed. Only the phenoxyethyl ester caused elevations of both striatal and tuberculum olfactorium HVA and DOPAC, greater than those measured following L-dopa administration. Overall the m trifluoromethylbenzyl, phenylethyl, p-chlorophenylethyl and p-methoxyphenylethyl ester prodrugs produced greater elevations of striatal and tuberculum olfactorium HVA, but not DOPAC, compared with L-dopa. The administration of the 2 tetrahydropyranyl-methyl derivative only enhanced striatal HVA and striatal and tuberculum olfactorium DOPAC concentrations. Changes of HVA and DOPAC tissue concentrations following administration of the 2-hydroxypropyl, n-propyl, methyl, ethyl and 2-(1-methoxy)propyl ester prodrugs were comparable with those produced by the administration of L-dopa itself. The alterations in striatal and tuberculum olfactorium HVA and DOPAC levels observed did not correlate with the ability of these compounds to elicit locomotor activity in reserpinized mice. PMID- 2891819 TI - Isolated tissue and binding studies of YM-17690, a novel and non-analogous leukotriene agonist. AB - YM-17690, 3-[4-carboxymethoxy-3-[p-(4-phenylbutoxy) benzamido]phenyl]propionic acid, produced a dose-dependent contraction of guinea-pig ileum and its EC50 value was 1.6 X 10(-8) M. The response was not affected by pretreatment with atropine, mepyramine, indomethacin, dazoxiben and AA-861 (a 5-lipoxygenase inhibitor), but was inhibited by FPL-55712 (an LTD4 and LTE4 antagonist). YM 17690 induced dose-dependent contractions of guinea-pig lung parenchyma and trachea with EC50 values of 3.9 X 10(-9) and 2.2 X 10(-8) M, respectively. Pretreatment of these tissues with FPL-55712 resulted in a parallel shift of the YM-17690 dose-response curves to the right. The pA2 values for FPL-55712 in lung parenchyma and trachea were 7.41 and 8.21, respectively, and the slopes of the regression lines of Schild plots were 1.00 and 1.02, respectively. YM-17690 produced a dose-dependent inhibition of [3H]LTD4 binding to guinea-pig lung membranes and its pKi value was 9.28. However, the compound showed only 25% inhibition of [3H]TLC4 binding to guinea-pig hippocampus membranes, even at 10( 5) M. These results suggest that YM-17690 is a selective leukotriene (LTD4 and LTE4) agonist and that it will therefore be a valuable tool in the study of actions of leukotrienes and for the characterization of their receptors. PMID- 2891820 TI - The effect of prostaglandins on gastric parietal and non-parietal secretion in the anaesthetized rat. AB - The effects of prostaglandin E2 (PGE2), 16,16-dimethyl prostaglandin E2 (dmPGE2) and prostaglandin F2 alpha (PGF2 alpha) on gastric secretion have been examined in the anaesthetized rat. The prostaglandins stimulated the secretion of a non parietal juice which was rich in Na+ and Cl- with smaller amounts of K+ and HCO3 . Doses of the prostaglandins that stimulated gastric non-parietal secretion also inhibited histamine stimulated gastric acid secretion, and thus the same rank order of potency was obtained for the prostaglandins on the two secretory mechanisms, viz. dmPGE2 greater than PGE2 greater than PGF2 alpha. During the secretion of endogenous gastric acid the secretagogue effect of the prostaglandins on non-parietal secretion was diminished, and this effect appeared to be due to the presence of intraluminal acid since it was mimicked by application of exogenous HCl to the gastric mucosal surface. Thus, the present results show that prostaglandins affect both the parietal and non-parietal secretions in the rat stomach and that these mechanisms show some interdependence. PMID- 2891821 TI - Biodegradable microspheres: polyacryl starch microparticles as a delivery system for the antileishmanial drug, sodium stibogluconate. AB - Liver parasite burdens of Leishmania donovani in the mouse have been determined after treatment with intravenous administration of sodium stibogluconate in the free or carrier form. The carrier form, in which the drug was covalently bound to polyacryl starch microparticles, was up to 100x more effective than the free form in this murine model of visceral leishmaniasis. Empty microparticles had no effect on liver parasite burdens and the enhanced in-vivo antileishmanial activity of the carrier form of the drug was apparently due to passive drug delivery to the infected liver. PMID- 2891822 TI - Cytochrome P450 metabolic intermediate complex of nefopam. AB - NADPH-catalysed biotransformation of nefopam in liver microsomes obtained from phenobarbitone-pretreated rats leads to the formation of an inactive cytochrome P450 metabolic intermediate (MI) complex. This complex can be detected spectrophotometrically by an absorbance maximum at 459 nm. The extent of the in vitro MI complexation of 33 microM nefopam, a cyclic analogue of orphenadrine, was almost equal to the extent of the in-vitro MI complexation of 33 microM tofenacine, the mono-N-demethylated metabolite of orphenadrine. The time course of the MI complexation of nefopam and studies with two of its major metabolites suggest an initial biotransformation, which has to occur before MI complexation can take place. Maximal MI complexation of nefopam occurred at approximately 25 microM, whereas the MI complexation could not be detected at 100 microM nefopam. PMID- 2891823 TI - Relationship between antipyrine elimination rate constant, clearance and volume of distribution in the rat. AB - While the relationship between the inverse of antipyrine half-life and clearance has been shown to be approximately linear in man, a recent report indicated that there was no significant relationship between antipyrine elimination rate constant (lambda) and clearance (CL) in the rat. Since this relationship is critical to the use of non-invasive methods to estimate drug metabolizing capacity, we have re-examined the relationship between lambda and CL in the rat. A significant correlation (r = 0.887) was found between antipyrine lambda and CL, while only a weak relationship (r = 0.442) was found between lambda and volume of distribution. These data support the use of non-invasive methods to estimate antipyrine elimination in the rat when invasive methods need to be avoided. PMID- 2891824 TI - Effect of ibuprofen and indomethacin on human plasma melatonin. AB - Ibuprofen reduced human plasma melatonin (MT) after 2 h when administered orally (400 mg) at 2400 h. Increasing plasma concentrations correlated well with increasing inhibition of serum MT levels during this time. Maximum plasma ibuprofen coincided with minimum plasma MT in 3 out of 4 volunteers. Although two volunteers exhibited a partial recovery in MT levels, concentrations after 6 h were significantly less than 0600 h values in drug-free volunteers. Administration of ibuprofen (400 mg) at 1800 h delayed the nocturnal surge of plasma MT. When a slow release preparation of indomethacin (75 mg) was administered at 1800 h, the dark phase rise of plasma MT was completely prevented. Thus the longer acting cyclooxygenase inhibitor exhibited a longer lasting inhibition of plasma MT concentration. PMID- 2891825 TI - Metabolic N-oxidation of metronidazole. AB - Metronidazole when treated at the N-3 nitrogen with a mixture of hydrogen peroxide and acetic acid, or liver homogenate preparations, yields the N-3 oxide as identified by thin-layer chromatographic analysis on silica gel G, RF 0.62 in ethanol-chloroform-ammonia (50:49:1), by chemical reduction with sulphur dioxide, and by ultra-violet spectrophotometry and nuclear magnetic resonance spectroscopy. Incubation of metronidazole at 37 degrees C with rat liver 10,000g supernatant fortified with cofactors gave a product with identical chromatographic and UV spectral data suggesting that metronidazole like other tertiary amine drugs undergoes microsomal N-oxidation. PMID- 2891826 TI - Rhein: an anthraquinone that modulates superoxide anion production from human neutrophils. AB - Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid), the active metabolite of diacetylrhein, which has been reported as an effective antirheumatic drug in man, inhibited superoxide anion production from human neutrophils challenged with N formylmethionyl-leucyl-phenylalanine (FMLP: IC50, 2 x 10(-5) M) and A23186 (IC50, 10(-5) M), but not with phorbol myristate acetate. In the same concentration range (10(-6)-10(-3) M), the drug did not affect oxy-radical production by a cell free hypoxanthine-xanthine oxidase system and exerted weak inhibitory effects on FMLP-evoked lysosomal enzyme release. Rhein inhibitory effects on neutrophil functioning may contribute to the overall therapeutic activity of the parent drug, diacetylrhein. PMID- 2891827 TI - Choice and concentration of contractile agent influence responses of rat aorta to vascular relaxant drugs. AB - Concentration-response (relaxation) curves to diltiazem, forskolin, isobutylmethylxanthine (IBMX), procaterol, isoprenaline and sodium nitrite were obtained on isolated ring preparations of rat aorta contracted either submaximally or maximally with noradrenaline or KCl. Diltiazem was more potent on KCl-contracted than on noradrenaline-contracted preparations whether the preparations were submaximally or maximally contracted. The other relaxant drugs were at least 20-fold less potent against KCl than against noradrenaline, but only on maximally contracted preparations. On submaximally-contracted preparations there was no potency difference between preparations contracted with these two contractile agents. Increasing the KCl concentration had a marked influence on the location of the concentration-response (relaxation) curves to all the drugs except diltiazem. This influence was different for drugs that act via cyclic AMP and those that act via cyclic GMP. It is concluded that both the choice of contractile agent (noradrenaline or KCl) and the concentration (especially of KCl) influence relaxant responses of rat aorta to vasodilator drugs. PMID- 2891828 TI - Interactions of aminoglutethimide with analgesics using antinociceptive tests in mice. AB - The action of aminoglutethimide in alleviating bone pain in women with metastatic breast cancer may be due to either an inherent analgesic effect or an interaction with other analgesic drugs. These possibilities have been investigated in mice by conventional antinociceptive tests. In the abdominal constriction test, aminoglutethimide alone had a dose-related antinociceptive activity. A low dose (which had no pharmacological activity) when co-administered with an effective sub-maximal dose of the analgesic, potentiated the effects of the non-steroidal anti-inflammatory drugs (NSAIDs) tested. In the tail immersion test, aminoglutethimide was inactive and did not enhance the antinociceptive activity of the centrally acting analgesics. As cytochrome P450-dependent routes which are inhibited by aminoglutethimide are not involved in the metabolism of the NSAIDs studied, an interaction at the drug metabolism level cannot explain these results. The NSAID-like activity of aminoglutethimide provides some evidence that the drug's mode of action may involve more than the suppression of oestrogen biosynthesis. PMID- 2891829 TI - Effect of pre-existing inflammation on carrageenan-induced paw oedema in rats. AB - Twenty-four hours after injection of carrageenan into one hind paw, injection of the same amount into the contralateral paw produced a significantly attenuated inflammatory response. However, when the second injection was given 7 days later, the inflammation induced in the contralateral paw was comparable with the initial response to carrageenan. A time-course study of carrageenan-induced inflammation in rats showed that significant oedema persisted 24 h after carrageenan administration and complete recovery was achieved in 7 days. The attenuated inflammatory response in the contralateral paw after 24 h was antagonized by bilateral adrenalectomy and chemical sympathectomy induced by 6-hydroxydopamine. Carrageenan-induced paw oedema was also significantly less in rats with subacute inflammation induced by the croton oil granuloma pouch technique. This attenuated response was antagonized by pretreatment of the rats with metyrapone, an inhibitor of adrenocorticoid synthesis, and by 6-hydroxydopamine. It is likely that the pre-existing acute or subacute inflammation attenuates the inflammatory response of carrageenan, by acting as a stressor, inducing activation of the sympatho-adrenal system. PMID- 2891830 TI - A study of PAF-induced ocular inflammation in the rat and its inhibition by the PAF antagonist, L-652,731. AB - A significant inflammatory reaction in the rat conjunctiva followed the subconjunctival injection of synthetic platelet activating factor (PAF) in doses which ranged from 10 ng to 1 microgram, an inflammatory response being evaluated as the increase in both tissue weight and extravasation of Evans blue dye in the conjunctival tissue. Inflammation was still present 6 h after the injection of 0.1 microgram of PAF. Orally administered indomethacin or BW 755C failed to alter the response to 0.1 microgram of PAF. In contrast, the PAF-induced inflammation was blocked by the oral administration of the PAF receptor antagonist, L-652,731, a dose as low as 5 mg kg-1 eliciting a significant inhibition. The topical administration of L-652,731, (two doses of 100 micrograms as a 1% suspension), elicited a slight, but significant blockade of 23%. Its antagonistic action was more striking when it was co-injected subconjunctivally with 0.1 microgram of PAF, a dose as low as 3 micrograms evoking a significant blockade. The topical administration of 0.1 microgram of PAF did not elicit a significant inflammatory reaction and this contrasts with the results obtained after its subconjunctival injection. PMID- 2891831 TI - Distribution and urinary excretion of the desethylmetabolites of chloroquine in the rat. AB - The tissue distribution of desethylchloroquine and bisdesethylchloroquine has been studied in rats after single intraperitoneal administration of the drugs at a dose of 10 mg kg-1. Concentrations of the chloroquine metabolites in the liver, heart, lungs, kidney and spleen were 34 to 250 times higher than their plasma concentrations 24 h after the drugs had been injected. Urinary excretion of the drugs was studied in rats after single intravenous administration of 2.5, 5 or 10 mg kg-1 doses. The total estimated urinary excretion of desethylchloroquine and bisdesethylchloroquine was 25 and 64% respectively of the administered dose, with the maximum urinary excretion occurring on the first day. The results show that the desethylmetabolites of chloroquine are concentrated in the tissues in the same manner as the parent compound. PMID- 2891832 TI - Dipole-mediated hydrogen bonding interactions between cimetidine analogues and the histamine H2 receptor. PMID- 2891833 TI - Penetration of diazepam and the non-peptide CCK antagonist, L-364,718, into rat brain. PMID- 2891834 TI - Proceedings of the Tenth Annual APON Conference. A decade of progress, a future of promise. October 8-11, 1986, Baltimore, Maryland. PMID- 2891835 TI - Exogenous corticosterone acetate attenuates the hypotension induced by ganglion blockade in conscious Long Evans and Brattleboro rats. AB - The effects of acute administration of corticosterone acetate (7.5 mg/kg bolus; 5 mg.kg-1h-1 infusion) on plasma corticosterone levels and blood pressure (BP) responses to hypotension induced by ganglion blockade (with pentolinium) were studied in conscious Long Evans and Brattleboro (vasopressin-deficient) rats. Steroid infusion raised plasma corticosterone levels similarly in both strains of rat, but there was no effect on resting BP. However, the fall in BP after pentolinium administration was less in the steroid-treated groups of both strains than in their vehicle-injected counterparts. During infusion of pentolinium the ensuing recovery in BP was abolished by captopril administration. Steroid treatment did not affect this recovery but did attenuate the hypotensive effects of captopril. In Long Evans rats, only, there was a further vasopressin-mediated, recovery in BP during the infusion of pentolinium and captopril. This recovery was not accentuated by the presence of the steroid. In a further experiment, infusion of corticosterone acetate after the onset of hypotension (induced by pentolinium, captopril and d(CH2)5DAVP in Long Evans rats or by pentolinium and captopril in Brattleboro rats) caused a progressive increase in BP in both strains. These findings demonstrate a pressor action of corticosterone acetate which is apparent after hypotension induced by ganglionic blockade and which does not necessarily involve any interaction with the renin-angiotensin system or vasopressin. PMID- 2891836 TI - Comparison of antinicotinic activity by neosurugatoxin and the structurally related compounds. AB - Neosurugatoxin (NSTX) which contains two sugars (myoinositol and xylopyranose) and bromine in the chemical structure, has been shown previously to be a selective antagonist of nicotinic receptors in guinea pig ileum and in murine brain. To study the role of sugar moiety and bromine in the antinicotinic activity by NSTX, we have examined the action of NSTX (compound I) and the structurally related compounds (compound II, III and IV) on the nicotine-induced contraction of guinea pig isolated ileum and on specific [3H]nicotine binding in rat forebrain membranes. Among four compounds examined, compound I was the most potent in inhibiting the nicotine-induced contraction of guinea pig isolated ileum (pA2 = 9.1 +/- 0.1, pD2' = 8.0 +/- 0.1) and also in inhibiting specific [3H]nicotine binding in rat forebrain (IC50 = 83 +/- 9 9 nM). Compared to compound I, compound II and III which are devoid of one and two sugars, respectively, in the chemical structure of compound I were 2 or 3 times less potent in the antinicotinic activity in both tissues, and compound IV which lacks bromine in addition to two sugars was two orders of magnitude less potent. Thus, the present study demonstrates that bromine rather than sugar moiety in the chemical structure of compound I (NSTX) is an important determinate of its high affinity for nicotinic receptors. PMID- 2891837 TI - Prevention of aspirin-induced gastric mucosal injury by histamine H2 receptor antagonists: a crossover endoscopic and intragastric pH study in the dog. AB - Histamine H2 receptor antagonists have been reported to protect the gastric mucosa of animals and humans against aspirin-induced damage. It is unclear, however, whether this protective effect can be observed at doses less than those needed to markedly inhibit gastric acid secretion. We have developed a single dose endoscopic assay system of aspirin-induced gastric mucosal injury in normal conscious dogs. In this model, severe gastric mucosal injury and a decrease in the pH of the gastric luminal contents were consistently demonstrated 2 h after the oral administration of 100 mg/kg of aspirin. Pretreatment with three histamine H2 receptor antagonists (cimetidine, ranitidine, BMY-25271), prevented both of these effects in a dose-related manner. All three H2 receptor antagonists reduced gastric mucosal injury only at doses that were greater than those required to prevent the aspirin-induced decrease in gastric luminal pH or to inhibit histamine-stimulated gastric acid secretion in Heidenhain pouch dogs. Plasma levels of aspirin were not altered by histamine H2 receptor antagonism. These results indicate that acid inhibition is an important component of the mechanisms whereby histamine H2 receptor antagonists protect the gastric mucosa from aspirin-induced damage in the dog. PMID- 2891838 TI - Neuropeptide Y release from the adrenal medulla after cholinergic receptor stimulation. AB - Peripheral nerves as well as chromaffin cells have been shown to contain neuropeptide Y (NPY), a 36 amino acid peptide that exhibits potent stimulatory actions on vascular smooth muscle. Because NPY-like immunoreactive material (NPY IR) is stored in chromaffin granules we chose to investigate, using the retrogradely perfused bovine adrenal gland, whether nicotinic cholinergic receptor stimulation results in the secretion of this material. In addition we monitored the release of [Met5]-enkephalin-like immunoreactive material (ME-IR), which has been demonstrated to be released from the bovine adrenal medulla. NPY IR and ME-IR were measured using antisera prepared from hemocyanin conjugates of the peptides. Increasing concentrations of acetylcholine (1 X 10(-6) M-5 X 10(-5) M), infused in the presence of 1 X 10(-5) M physostigmine, produced significant increases in NPY-IR and ME-IR release. Hexamethonium (5 X 10(-4) M) antagonized the release of both of these substances, whereas atropine (5 X 10(-7) M) did not. The role of the nicotinic cholinergic receptor in this process was established further by examining the effects of 1,1-dimethyl-4-phenylpiperazinium. Increasing concentrations of 1,1-dimethyl-4-phenylpiperazinium (1 X 10(-6) M-5 X 10(-5) M) also stimulated the release of NPY-IR and ME-IR. Analysis of the perfusate by reverse phase liquid chromatography revealed the presence of four peaks of NPY IR. A major peak coeluted with authentic NPY. These data demonstrate that NPY-IR can be released through stimulation of the nicotinic cholinergic receptor. The adrenal medulla appears to be one of the sources for circulating NPY-IR. PMID- 2891839 TI - Discriminative stimulus properties of intragastrically administered d-amphetamine and pentobarbital in rhesus monkeys. AB - Rhesus monkeys were trained to discriminate intragastrically administered d amphetamine (AMPH) or pentobarbital (PENTO) from saline using a signaled shock avoidance trail procedure. All monkeys maintained criterion levels (greater than 90% drug-appropriate responding) throughout the duration of the study during training sessions. In the AMPH experiment, the anorectics diethylpropion, mazindol, phendimetrazine, phenmetrazine and phentermine completely substituted for the training dose of AMPH. The atypical antidepressant bupropion and the psychomotor stimulant methylphenidate also completely substituted for AMPH. Other anorectics including benzphetamine, clortermine, fenetylline, mefenorex and the psychomotor stimulant pemoline that share some pharmacological properties with AMPH substituted for AMPH in some, but not all, of the monkeys tested. The anorectics fenfluramine and chlorphentermine failed to substitute for AMPH. Drugs from other pharmacological classes such as morphine, diazepam, nortripyline and PENTO also failed to substitute for AMPH, indicating pharmacological specificity. In the PENTO experiment, the benzodiazepines alprazolam, bromazepam, diazepam, flurazepam, halazepam, lorazepam, midazolam, oxazepam, temazepam and triazolam and the sedatives methaqualone and phenobarbital completely substituted for the training dose of PENTO. The nonbenzodiazepine anxiolytic CL 218,872 only partially substituted for PENTO. In addition, morphine and AMPH failed to substitute for PENTO, indicating pharmacological specificity. In summary, drugs delivered intragastrically functioned as discriminative stimuli in a drug-class specific manner. The ability to use drugs delivered by this route as discriminative stimuli provides a way to compare anorectic drugs to AMPH or sedative drugs to PENTO under conditions that resemble the mode of human consumption to determine whether these drugs are likely to be associated with AMPH-like or PENTO-like drug dependence. PMID- 2891840 TI - Behavioral studies with anxiolytic drugs. IV. Serotonergic involvement in the effects of buspirone on punished behavior of pigeons. AB - Interactions of the nonbenzodiazepine anxiolytic, buspirone, with serotonin (5 HT) were studied using behavioral and neurochemical procedures. Punished responding was studied in pigeons as this behavior is a generally acknowledged preclinical predictor of anxiolytic activity and because buspirone increases punished responding of pigeons with greater potency and efficacy than in other species. Keypeck responses were maintained under either fixed-interval or fixed ratio schedules of food presentation; every 30th response produced a brief electric shock and suppressed responding (punishment). Buspirone (0.1-5.6 mg/kg i.m.) produced dose-related increases in punished responding which reached a maximum at 1 mg/kg. A serotonin agonist, MK-212 (0.01 mg/kg), antagonized whereas the 5-HT antagonist, cyproheptadine (0.01 mg/kg), potentiated the effects of buspirone without having behavioral effects of their own. The characteristics of [3H]-5-HT binding in pigeon brain membranes were similar to results reported in mammalian brain. Neither buspirone, MJ-13805 (gepirone, a related analog), nor MJ 13653 (a buspirone metabolite), significantly affected [3H]-5-HT binding and none of the compounds appreciably inhibited uptake of [3H]-5-HT into pigeon cerebral synaptosomes. Hill coefficients significantly less than unity for all drugs except 5-HT suggested multiple serotonergic binding sites for buspirone and analogs. Buspirone and MJ-13805 (1 nM) inhibited [3H]ketanserin binding (a measure of 5-HT2 binding sites) in pigeon cerebrum with Ki values above 10(-6) M. The number of [3H]ketanserin binding sites was estimated to be 109 fmol/mg of protein in pigeon cerebrum compared to 400 fmol/mg of protein in rat cerebrum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891841 TI - Enhanced endogenous neurotransmitter overflow in the isolated perfused rat kidney after chronic epinephrine administration: lack of a prejunctional beta adrenoceptor influence. AB - This study examines stimulus-induced overflow of endogenous catecholamines from the isolated perfused kidney of rats after epinephrine (EPI) administration at 100 micrograms/kg/hr for 6 days via s.c. implanted osmotic minipumps. This regimen resulted in the incorporation of EPI into renal catecholamine stores and the co-release of EPI with norepinephrine during periarterial nerve stimulation. Stimulus-induced (1 Hz) absolute and fractional overflows of neurotransmitter were significantly greater in the EPI-treated rats. These differences in overflow were not altered by uptake blockade. Alpha adrenoceptor blockade with phentolamine (10(-9)-10(-5) alone increased overflow in a dose-dependent manner in both groups, although to a greater extent in the EPI-treated group. However, in the presence of 1 microM propranolol the effect of phentolamine in the EPI treated group was greatly reduced such that, in the presence of propranolol, phentolamine was less effective in the EPI-treated vs. vehicle-treated rats. Beta adrenoceptor blockade alone with propranolol (10(-9)-10(-6) M) did not alter stimulus-induced overflow in either group but propranolol dose dependently reduced fractional overflow in the EPI-treated rats when the experiments were done in the presence of 10 microM phentolamine. It is concluded that the enhanced fractional overflow observed in the kidneys of EPI-treated rats was not due to beta adrenoceptor activation, but rather, a reduced influence of the prejunctional alpha adrenoceptor-mediated negative feedback loop. Beta adrenoceptor activation by neurally released EPI does not appear to modulate stimulus-induced overflow unless the dominant inhibitory alpha adrenoceptor mechanism is inactivated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891843 TI - Mechanisms for the hepatic uptake of organic cations. Studies with the muscle relaxant vecuronium in isolated rat hepatocytes. AB - In hepatobiliary transport of organic cations some remarkable differences have been reported between the monovalent compounds (prototype procainamidethobromide) and the potentially bivalent cations, containing a second quaternary ammonium group or a protonated tertiary amine function (prototype d-tubocurarine). In order to characterize the hepatic uptake mechanism for such bivalent cations in more detail, we studied the uptake of the steroidal muscle relaxant vecuronium in isolated rat hepatocytes. Uptake occurred by both a saturable (Vmax = 181 pmol/min x 10(6) cells, Km = 15 microM) and a nonsaturable process (rate constant = 1.10 pmol/min/10(6) cells/microM). The uptake of vecuronium was reduced by various metabolic inhibitors and by sulfhydryl-blocking agents. The transport system showed temperature dependency with an activation energy of 85 kJ/mol. Sodium replacement by lithium or choline in the extracellular medium had no effect on the uptake of vecuronium. Replacement of sodium chloride by sucrose led to a decrease of the uptake, whereas chloride replacement by bicarbonate or iodide stimulated the vecuronium uptake. These data point to a significant anion dependency of the uptake system and indicate electroneutral uptake of vecuronium. The uptake of vecuronium was inhibited by a variety of hepatic transport model compounds, including bile acids, uncharged compounds and high molecular weight organic cations. Low molecular weight monovalent cations had no effect on the uptake of vecuronium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891842 TI - Toxicity of H2-receptor antagonists to isolated rat hepatocytes: structure activity relationships. AB - Oxmetidine is a potent and specific antagonist of the histamine H2-receptor. Oxmetidine is also cytotoxic to isolated rat hepatocytes through inhibition of mitochondrial oxidative phosphorylation. The purpose of this investigation was to test a variety of H2-receptor antagonists that are structural analogs of oxmetidine in an attempt to identify a critical structural component or a physicochemical property of the molecule which may be responsible for cytotoxicity. Six histamine receptor H2-antagonists were tested. The minimum drug concentrations that caused 100% cell death (leakage of intracellular lactate dehydrogenase and loss of intracellular potassium) ranged from 0.87 to 22.50 mM for the analogs tested. At toxic concentrations, two of the least potent analogs, SK&F 92909 and SK&F 9205A both caused a rapid decrease in hepatocyte O2 consumption and ATP content which occurred before any evidence of cell injury. The potency of these molecules as cytotoxicants to isolated hepatocytes did not correlate with their potency as histamine H2-receptor antagonists whereas there was a significant correlation between increasing potency and increasing octanol/water partition coefficients. These data suggest that lipid solubility may be a key factor in the cytotoxicity of this class of drugs to isolated rat hepatocytes. PMID- 2891844 TI - Stimulation of opiate receptors in the dorsal pontine tegmentum inhibits reflex contraction of the urinary bladder. AB - In urethane-anesthetized rats the i.v. administration of the potent short-acting opioid, fentanyl, elicited inhibition of rhythmic spontaneous reflex increases in vesical pressure (VP) evoked by urinary bladder distension. The duration of fentanyl-induced inhibition was dose-related between 0.8 and 8.0 micrograms/kg i.v. Pretreatment with the opiate receptor antagonist, naloxone HCl (250 micrograms/kg i.v.), antagonized completely fentanyl's effect on VP rhythm. Results similar to those obtained with fentanyl were observed after the bilateral stimulation of opiate receptors in the dorsolateral tegmental-subceruleus region of the pons (DLT-SC region) with D-Ala2-Met5-enkephalinamide (DAMA) microinjections. These inhibitory effects were dose-related and significant between 1.0 and 100.0 ng/site. DAMA in the DLT-SC did not alter basal cardiorespiratory parameters. The systemic and local administration of naloxone reversed rapidly the VP effects elicited by DAMA in the DLT-SC region. Naloxone alone, administered either i.v. or locally in the DLT-SC region, increased the frequency of spontaneous reflex increases in VP. Moreover, pretreatment of the DLT-SC region with naloxone microinjections significantly (55% reduction) decreased the duration of fentanyl (8.0 micrograms/kg i.v.)-induced inhibition of VP rhythm. Neurons in DLT-SC region whose discharge increased just before and throughout spontaneous increases in VP (vesical contraction-related units), were inhibited rapidly and completely by the systemic administration of fentanyl. However, fentanyl elicited a prolonged decremental discharge in neurons of the DLT-SC region with discharge patterns related to vesical relaxation (vesical relaxation-related units).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891846 TI - Spinal infusion of opiate and alpha-2 agonists in rats: tolerance and cross tolerance studies. AB - Intrathecal morphine or ST-91, an alpha-2 agonist, produce potent antinociception in a number of animal models. Using osmotic minipumps and a new Y-catheter technique, we show that chronic intrathecal (i.t.) infusion of morphine (2, 6 or 20 nmol/microliter/hr) or ST-91 (3, 10 or 30 nmol/microliter/hr) in rats produces a dose-dependent increase in hot-plate latency 1 day after pump implant. By 4 to 5 days after initiation of chronic infusion of either drug, hot-plate latencies do not differ from saline-infused controls. Rats rendered tolerant to one of the three chronic i.t. morphine doses (2, 6 or 20 nmol/microliter/hr) and tested at 7 days after initiation of infusion with a bolus i.t. dose of morphine, show a dose dependent rightward shift in hot-plate dose-response curves. The two lower doses of chronic i.t. infusions of morphine produce parallel shifts of the subsequent i.t. administered morphine dose-response curves, but the highest chronic i.t. dose of morphine (20 nmol/microliter/hr) produces a significantly greater slope of the subsequent i.t. administered morphine dose-response curve. Animals exposed to chronic i.t. infusion of one of three doses of ST-91 (3, 10 or 30 nmol/microliter/hr) display a parallel, dose-dependent rightward shift to a subsequent bolus i.t. injection of ST-91. Rats rendered tolerant to chronic i.t. infusions of ST-91 showed no difference in the response to i.t. administered morphine hot-plate dose-response curves as compared to saline infused controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2891845 TI - Electrophysiological effects of BMY 14802, a new potential antipsychotic drug, on midbrain dopamine neurons in the rat: acute and chronic studies. AB - The present experiments compared the ability of a new potential antipsychotic drug, BMY 14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine- butanol), to alter the electrophysiological activity of midbrain dopamine (DA) neurons in the rat substantia nigra (A9) and ventral tegmental area (A10). Intravenous administration of BMY 14802 reversed the rate-suppressant effects of the DA agonist apomorphine on both A9 and A10 DA neurons; however, this reversal occurred at significantly lower doses in A10 than in A9. These effects of BMY 14802 appeared not to be mediated by DA receptors because, unlike the established antipsychotic drugs haloperidol and clozapine, BMY 14802 pretreatment failed to block apomorphine-induced suppression of A10 DA cells. Repeated s.c. administration (28 days) of BMY 14802 (2.5-10.0 mg/kg) reduced the number of spontaneously active A10 DA cells recorded per electrode track without affecting the number of A9 DA cells. This inactivation of A10 DA neurons was only partially reversed by the administration of apomorphine. Thus, it is uncertain as to whether this effect was produced by depolarization block as occurs during repeated administration of known antipsychotic drugs. These findings indicate that BMY 14802 influences DA neurotransmission by a nondopaminergic (perhaps sigma opioid) mechanism. The more potent effect of BMY 14802 on A10 DA neurons suggests that this novel compound may exert antipsychotic effects without producing significant extrapyramidal side effects. PMID- 2891847 TI - Inhibitory effects of diltiazem on vasoconstrictor responses in the cat. AB - The effect of diltiazem on vasoconstrictor responses was investigated in the feline mesenteric vascular bed under conditions of controlled blood flow. Diltiazem inhibited vasoconstrictor responses to sympathetic nerve stimulation, tyramine and norepinephrine suggesting that responses to both nerve-released and exogenous norepinephrine are dependent in part on an extracellular source of calcium. The calcium entry antagonist inhibited vasoconstrictor responses to alpha 1 and to alpha 2 adrenoceptor agonists over a wide range of concentration. Diltiazem also inhibited mesenteric vasoconstrictor responses to angiotensin II, vasopressin, prostaglandin F2 alpha and KCl. The inhibitor effects of diltiazem on vasoconstrictor responses to nerve stimulation and the pressor agents were reversible, and all responses returned to control value 30 to 45 min after the infusion of the calcium entry antagonist. The present data suggest that the inhibitory effects of diltiazem on responses to sympathetic nerve stimulation are postjunctional in nature, as responses to nerve-released and exogenous norepinephrine and nonadrenergic pressor agents are reduced to a similar extent. The present results suggest that vasoconstrictor responses to neuronally released and exogenous norepinephrine, as well as agents which activate membrane receptors or depolarize vascular smooth muscle in the feline mesenteric vascular bed, are dependent in part on an extracellular source of calcium. The inhibitory effects of diltiazem on vasoconstrictor responses to sympathetic nerve stimulation and pressor hormones may be relevant to the antihypertensive actions of this calcium entry antagonist. PMID- 2891848 TI - Using neuroleptics. PMID- 2891849 TI - Characteristics of long term benzodiazepine users in general practice. AB - In a practice of 6000 patients, all long term users of day time benzodiazepine tranquillizers were identified and matched for age and sex with controls. Patients and controls were asked to complete two postal questionnaires, one to measure a number of neurotic personality traits and the other to record details of personal history thought to be relevant. Tranquillizer users were also sent a third questionnaire which surveyed their attitudes to reliance on tranquillizers. Long term users of benzodiazepines had significantly higher scores for anxiety and other neurotic traits but their personal histories showed few significant differences from those of controls. Patients reliant on benzodiazepines seem to be a distinct, more ;neurotic' sub-group of the practice population although their lives have not been any more disturbed. Most patients thought that tranquillizers had helped them but many felt uneasy about being reliant on them. Follow up showed a trend towards spontaneous discontinuing of the tablets. PMID- 2891850 TI - Polyarteritis nodosa presenting as meningoencephalitis. PMID- 2891851 TI - Beta-blockers in myocardial infarction. PMID- 2891852 TI - Improved delivery through biological membranes. 26. Design, synthesis, and pharmacological activity of a novel chemical delivery system for beta-adrenergic blocking agents. AB - Novel ketoxime analogues of known beta-blockers (propranolol, timolol, carteolol) were synthesized and tested as potential site-specific chemical delivery systems. It was assumed that a hydrolysis-reduction sequence could produce the active beta blockers in the iris-ciliary body. It was found that some of these bioprecursors are remarkably active in reducing intraocular pressure in rabbits. The ketoxime derivative of propranolol is more effective and much less irritant than its parent beta-blocker. While the ketoximes also displayed activity on isoprenaline induced tachycardia after iv administration, they were void of activity when given orally. Propranolol was found for a prolonged time and in significant concentrations in the rabbit's eye following topical administration of its ketoxime precursor; however, the inactive ketoximes apparently were not converted to the corresponding beta-blockers in the eye. A correlation was found between the physicochemical properties of the ketoximes and their conversion to the amino alcohol and thus their subsequent activity. The results suggest that at least some of the ketoxime precursors could have a use as antiglaucoma agents without systemic side effects. PMID- 2891853 TI - A novel class of potential central nervous system agents. 3-Phenyl-2-(1 piperazinyl)-5H-1-benzazepines. AB - A series of 3-phenyl-2-piperazinyl-5H-1-benzazepines and related compounds were synthesized and evaluated for potential neuroleptic activity. The preparation of these compounds was carried out by 2,3-dichlorination of 3-phenyl-2,3,4,5 tetrahydro-1H-1-benzazepin-2-ones with phosphorus pentachloride followed by amination and concurrent dehydrochlorination. Compounds having the 4-chloro or 4 fluoro substituent in the 3-phenyl group were found to possess the neuroleptic like activity. Among them, 2-(4-methyl-1-piperazinyl)-3-(4-fluorophenyl)-5H-1 benzazepine dihydrochloride (23) was comparable to chlorpromazine in inhibiting exploratory activity, conditioned avoidance response, and self-stimulation response and more potent than chlorpromazine in antagonizing apomorphine-induced emesis. These neuroleptic effects may be based on an antidopaminergic property of the compound. In causing catalepsy or ptosis, however, 23 was weaker than chlorpromazine. Therefore, this ring system is of interest as a novel class of neuroleptics. Some compounds having the 7-chloro or 7-bromo substituent showed potent anticonvulsant effects against maximal seizures induced by electroshock or pentylenetetrazole. PMID- 2891854 TI - Potential antisecretory antidiarrheals. 1. Alpha 2-adrenergic aromatic aminoguanidine hydrazones. AB - Guanabenz, a centrally acting antihypertensive agent, has been shown to have intestinal antisecretory properties. A series of aromatic aminoguanidine hydrazones was made in an effort to separate the antisecretory and cardiovascular activities. Benzaldehyde, naphthaldehyde, and tetralone derivatives were synthesized. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and in the Ussing chamber using a rabbit ileum preparation. A number of compounds, including members of each structural class, were active upon subcutaneous administration in the rat. Active compounds were determined to be alpha 2-adrenergic agonists by yohimbine reversals of their Ussing chamber activities. The compound displaying the best separation of activities was the aminoguanidine hydrazone of 2,6-dimethyl-4-hydroxybenzaldehyde (20). PMID- 2891855 TI - Immunoprotective behaviour of plasma-membrane-associated antigens of axenic Entamoeba histolytica. AB - Immunisation of golden hamsters with plasma-membrane-associated antigens of a virulent subline of axenic Entamoeba histolytica strain NIH 200 V, entrapped in multilamellar phosphatidylcholine liposomes (MPL) or Freund's complete adjuvant (FCA), afforded protection against intrahepatic challenge with axenic amoebic trophozoites of the same strain. Amoebic liver abscess developed in 86% and 80% of the animals that received empty liposomes or buffer emulsified in FCA but in none of the animals that received plasma-membrane-antigen vaccines. All the immunised animals had significantly higher levels (p less than 0.001) of antibodies to plasma-membrane components and significantly higher levels (p less than 0.001) of cellular sensitisation. Antibody-dependent macrophage-mediated cytotoxicity against trophozoites was also found to be significantly greater (p less than 0.001) in immunised animals. Liposome-entrapped antigens stimulated the immune system of the host as well as, or better than, antigens administered with FCA. PMID- 2891856 TI - Renal enzyme activities in experimental ochratoxin A-induced porcine nephropathy: diagnostic potential of phosphoenolpyruvate carboxykinase and gamma-glutamyl transpeptidase activity. AB - Enzyme activities have been measured in needle biopsies from kidneys of pigs fed 1 ppm or 0.2 ppm of ochratoxin A for 1-5 wks. After feeding 1 ppm toxin for 1 wk, the activity of cytosolic phosphoenolpyruvate carboxykinase (PEPCK) was decreased by 40% and remained inhibited until the termination of the experiment (5 wk). The activity of gamma-glutamyl transpeptidase, a brush-border enzyme found in the proximal tubules, was reduced to a similar degree and remained inhibited. The activities of hexokinase, a cytosolic enzyme of general distribution in the nephron, and phosphate-dependent glutaminase, a distal tubule enzyme, were not affected. The biopsy results were confirmed by measurements in renal slices taken at the termination of the experiment, except that biopsy samples showed more variation in enzyme activity and a lower PEPCK activity. A guinea pig antibody against the cytosolic form of PEPCK was used to demonstrate that the mitochondrial form of the enzyme, which accounts for a considerable part of the total cellular activity, was not affected by ochratoxin A. When mitochondrial PEPCK activity present in the cytosolic fraction was accounted for, ochratoxin A was found to reduce PEPCK activity by 70-80%. The increase of ochratoxin A exposure from zero through 0.2 ppm to 1 ppm, which resulted in dose-dependent activity decrease of PEPCK and gamma-glutamyl transpeptidase, was accompanied by dose-dependent decrease of renal function, as measured by a reduction of maximal tubular excretion of para-aminohippurate per clearance of inulin (TmPAH/CIn) and an increase in glucose excretion. This suggest that these enzymes are sensitive indicators of ochratoxin A-induced porcine nephropathy. Assuming that porcine nephropathy represents a valid model of endemic (Balkan) nephropathy in humans, the measurement of cytosolic PEPCK and gamma-glutamyl transpeptidase activity in the kidney could be a sensitive test for ochratoxin A-induced disease in humans. PMID- 2891857 TI - Heterogeneity of opioid receptor binding in brain slices. AB - A methodological approach was established for the study of ligand binding to multiple opioid receptors in slices from rat brain striatum. Specific binding of radiolabeled opiates was resolved from total binding with enantiomers or excess unlabeled ligand. Equilibrium binding of triated etorphine, dihydromorphine, and ethylketocyclazocine, and competitive displacement of [3H]etorphine and [3H]dihydromorphine by the unlabeled opiates were used to assess both high and low affinity receptor sites. The high-affinity binding components of the radiolabeled opiates were characterized by linear Scatchard plots, Kd values of 2.8-3.7 nM, and binding site densities of 180-297 fmol/mg protein. The displacement of [3H]etorphine by morphine and ethylketocyclazocine displayed Hill coefficients of 0.62 and 0.47, respectively, and revealed receptor sites with much lower affinities than those described by the direct binding of these opiates. On the other hand, both morphine and ethylketocyclazocine displaced [3H]dihydromorphine with similar high potencies (apparent Kd's, 3-4 nM). The results support the feasibility of using brain slices as a cellular preparation to study opioid receptor mechanisms. PMID- 2891858 TI - Pharmacological characteristics of diazepam receptors in neurons and astrocytes in primary cultures. AB - Benzodiazepine binding sites in mouse astrocytes and neurons in primary cultures were labeled with [3H]diazepam (1.8 nM), and their inhibition by 14 different benzodiazepines and 3 benzodiazepine antagonists was studied. RO 5-4864, RO 7 3351, and, especially, the antagonist PK 11195 were much more potent in astrocytes than in neurons, whereas the opposite was true for the agonists alprazolam, clonazepam, flurazepam, RO 11-3128, and chlordiazepoxide, and, especially, the antagonists CGS-8216 and RO 15-1788. Flunitrazepam, diazepam, midazolam, RO 11-6893, and RO 5-2181 were about equipotent in the two cell types. The neuronal, but not the astrocytic, binding site showed stereospecificity. In astrocytes most of the drugs had pseudo-Hill coefficients close to one, whereas the pseudo-Hill coefficients in neurons, except for RO 5-4864 and PK 11195, were distinctly lower than one. Thus, the benzodiazepine binding sites had profoundly different pharmacological characteristics in neurons and in astrocytes. PMID- 2891859 TI - Effects of chronic propranolol treatment on hepatic adenylate cyclase system in the rat. AB - The biochemical aspects of hepatic beta-adrenergic receptors and adenylate cyclase activity in male adult rats were examined during chronic treatment of a beta-adrenergic antagonist, propranolol. The blockade of beta-adrenergic nervous systems for 7 to 10 days produced a considerable elevation of basal, glucagon, sodium fluoride, and 5'-guanylylimidodiphosphate, Gpp (NH)p-stimulated enzyme activity with a negligible response to a beta-adrenergic agonist, isoproterenol. There was no alteration in the density or the affinity of beta-adrenergic receptors for the agonist during the treatment. Guanine nucleotides have failed to induce a transformation of the higher affinity to the lower affinity state of beta-adrenergic receptors of the hepatic membrane derived either from control or the propranolol-treated animals. The activity of stimulatory guanine nucleotide regulatory proteins (Ns) in the enzyme, assessed by ADP-ribosylation was also not altered by the antagonist. These results suggest that the mechanism of the observed sensitization of adenylate cyclase induced by chronic beta-adrenergic blockade involves facilitation of Ns interaction with the catalytic subunit of the enzyme with no change in the beta-adrenergic receptor functions. PMID- 2891860 TI - Vasculitis in the lung. AB - Pulmonary vasculitis occurs most commonly in the collagen vascular diseases and in granulomatous pulmonary disease. In the collagen vascular group, vasculitis causes diffuse interstitial inflammation and subsequent fibrosis, resulting in interstitial radiographic patterns, especially in the lower lung fields. Vasculitis accompanied by granulomatosis typically produces focal inflammation and is, therefore, manifested as nodules and masses. The more typical collagen vascular diseases include rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and dermatomyositis. The most common vasculitis granulomatosis is Wegener's, with similar radiographic abnormalities occurring in lymphomatoid granulomatosis. Atypical examples of vasculitis pulmonary disease include ankylosing spondylitis, in which upper-lung field fibrobullous changes are seen. Periarteritis nodosa and Behcet's syndrome include abnormalities of large vessels and thromboembolic phenomena. Bronchocentric granulomatosis and allergic granulomatosis involve airway abnormalities as well as vasculitis and granuloma formation. PMID- 2891862 TI - Dicentric Y chromosome and mixed dysgenesis. AB - We report 4 cases of mixed gonadal dysgenesis with a karyotype containing a dicentric Y chromosome. All cases were mosaic with 45X and 46X, dic(Y) cell lines. Of the patients 1 had ambiguous genitalia and some features of Turner's syndrome, 2 had classical features of Turner's syndrome with normal female external genitalia and 1 had no features of Turner's syndrome but he presented with penoscrotal hypospadias, inguinal hernia and cryptorchidism. Female gender assignment and early total gonadectomy should be considered when a dicentric Y chromosome is present in cases of mixed gonadal dysgenesis. PMID- 2891861 TI - Genetic diversity of enzootic isolates of vesicular stomatitis virus New Jersey. AB - The RNA genomes of 43 vesicular stomatitis virus (VSV) isolates of the New Jersey (NJ) serotype were T1-ribonuclease fingerprinted to compare the extent of genetic diversity of virus from regions of epizootic and enzootic disease activity. Forty of these viruses were obtained from Central America during 1982 to 1985. The other three were older isolates, including a 1970 isolate from Culex nigripalpus mosquitos in Guatemala, a 1960 bovine isolate from Panama, and a 1976 isolate from mosquitos (Mansonia indubitans) in Ecuador. The data indicate that extensive genetic diversity exists among virus isolates from this predominantly enzootic disease zone. Six distinct T1 fingerprint groups were identified for the Central American VSV NJ isolates from 1982 to 1985. The 1960 VSV NJ isolate from Panama and the 1976 isolate from Ecuador formed two additional distinct fingerprint groups. This finding is in sharp contrast to the relatively close genetic relationship existing among VSV NJ isolates obtained from predominantly epizootic disease areas of the United States and Mexico during the same period (S. T. Nichol, J. Virol. 61:1029-1036, 1987). In this previous study, RNA genome T1 fingerprint differences were observed among isolates from different epizootics; however, the isolates were all clearly members of one large T1 fingerprint group. The eight T1 fingerprint groups described here for Central American and Ecuadorian viruses are distinct from those characterized earlier for virus isolates from the United States and Mexico and for the common laboratory virus strains Ogden and Hazelhurst. Despite being isolated 14 years earlier, the 1970 insect isolate from Guatemala is clearly a member of one of the 1982 to 1985 Central American virus fingerprint groups. This indicates that although virus genetic diversity in the region is extensive, under certain natural conditions particular virus genotypes can be relatively stably maintained for an extended period. The implications of these findings for the evolution of VSV NJ and epizootiology of the disease are discussed. PMID- 2891863 TI - Leads from the MMWR. Adult T-cell leukemia/lymphoma associated with human T lymphotropic virus type I (HTLV-I) infection--North Carolina. PMID- 2891864 TI - Role of neurotransmitter in forensic medicine (report III). A new analysis of inhibitory neurotransmitter amino acids in tissues and biological fluids by high performance liquid chromatography with electrochemical detection. PMID- 2891865 TI - KRAS2 as a genetic marker for lung tumor susceptibility in inbred mice. AB - An Eco-RI restriction fragment length polymorphism occurring in a DNA fragment containing the first exon of the murine KRAS2 gene was shown to correlate with the inherited susceptibility of inbred strains of mice to urethan (CAS: 51-79-6) induced pulmonary adenomas. Eco-RI digestion of murine DNA yielded four KRAS2 specific fragments. Polymorphic variation occurred in the smallest molecular weight fragment with alleles of either 0.70 or 0.55 kb in size. Genotyping of 14 inbred strains of mice revealed a correlation between KRAS2 Eco-RI polymorphic variation and the differential susceptibility among inbred strains to development of pulmonary adenomas. Strains with a high incidence of pulmonary adenomas, either spontaneously occurring or in response to carcinogen induction, had the 0.55-kb KRAS2 allele whereas adenoma-resistant strains had the 0.70-kb allele. Analysis of a series of recombinant inbred strains (AXB, BXA) that developed from reciprocal crosses between a highly susceptible strain (A/J) and a highly resistant strain (C57BL/6J) revealed a statistically significant threefold difference in lung tumor susceptibility on the basis of KRAS2 genotype. Further analysis of individual F2 mice of a C57BL/6 female X A/J male cross also demonstrated a threefold difference in tumor susceptibility on the basis of KRAS2 allelic variation. PMID- 2891866 TI - Use of vasoactive agents to increase tumor perfusion and the antitumor efficacy of drug-monoclonal antibody conjugates. AB - The effects of both alpha 1- and beta-adrenergic blocking agents on the vascular perfusion of tumors were studied with the ultimate goal of improving diagnosis and therapy of solid tumors with the use of monoclonal antibody (MAb) conjugates. With the use of a subcutaneously growing murine thymoma, it was demonstrated that nonselective and cardioselective beta-adrenergic blocking agents were capable of increasing threefold tumor-to-blood and tumor-to-liver perfusion of 125I-labeled MAbs. Subsequently, these beta-adrenergic blocking agents were found to increase the antitumor efficacy of idarubicin (Ida)-MAb conjugates. Conjugate-treated mice that also received beta-adrenergic blocking agents had a smaller mean tumor size and a greater number of regressions than mice receiving Ida-MAb conjugate alone. By contrast, prazosin HCl, an alpha 1-adrenergic blocking agent, and Cyclospasmol, a peripheral vasodilator, did not enhance the tumor perfusion and antitumor efficacy of 125I- or Ida-conjugated MAbs, and no vasoactive agent enhanced the antitumor effect of Ida when used alone. By their selective action on normal blood vessels, vasoactive drugs can change the tumor-to-normal tissue perfusion ratio, thereby enhancing the access of drug-MAb conjugates to tumors and increasing the effectiveness of tumor therapy with the use of drug-MAb conjugates. PMID- 2891867 TI - [Elevation of intraocular pressure following Nd-YAG laser capsulotomy. Pathogenesis and preventive therapy]. AB - Nd: YAG laser capsulotomy is a well-established method of opening an opacified posterior lens capsule after extracapsular cataract extraction. The most frequent complication following this procedure is a transient rise in intraocular pressure (IOP) occurring during the first few hours following treatment. In most cases the IOP returns to normal within 24 hours. Occasionally, however, it can increase excessively, causing a vision-threatening complication. The prospective study reported here dealt with the pressure elevation in 60 eyes of 60 patients and the characteristics of aqueous outflow in this critical phase. Tonometric and tonographic findings were compared under the influence of topical indometacin and beta-blocker in combination with pilocarpine 2%. Twenty eyes served as untreated controls. Topical indometacin pretreatment had no positive effect on IOP and aqueous outflow, while beta-blocker and pilocarpine 2% prevented a postoperative elevation of IOP. PMID- 2891868 TI - [Molecular genetic diagnosis in X chromosome-linked retinitis pigmentosa]. AB - Retinitis pigmentosa (RP) is the most common hereditary dystrophic disease of the retina. About 10% of the affected families show the X-linked trait. The close link observed between the gene locus (RP2) and a polymorphic DNA marker (DXS7) on the proximal short arm of the X-chromosome permits an indirect genotype diagnosis and can be helpful in carrier detection and genetic counseling. A case is presented in which the carrier risk of a female consultant dropped from 50% a priori to less than 2% by the use of clinical findings and DNA analysis. PMID- 2891869 TI - [Glucose level of the blood and its regulation in patients with hemorrhagic fever with renal syndrome]. PMID- 2891870 TI - [Human blood glutamic acid in exposure to elevated ammonia levels in the gaseous environment]. AB - Amino acid metabolism of men kept in a enclosed environment was investigated. A high concentration of ammonia produced a specific redistribution of free amino acids in plasma with the content of glutamic acid increasing by the end of study. The estimates of glutamic acid in blood can be used for assessing maximally allowable concentrations of ammonia in enclosed environments. PMID- 2891872 TI - [Toxicokinetic aspect of the potential use of sulfur hexafluoride in sealed quarters]. PMID- 2891871 TI - [Composition of the water obtained after its sanitary and hygienic use by men and women]. AB - The composition of wash water used by men and women was investigated. The results were exposed to multifactorial statistical analysis using the method of principal components. The investigation allowed the following conclusions to be made: 1) wash water used by men and women is comparable in composition; therefore the sex of the crewmembers of space vehicles can be disregarded when designing water reclamation systems; 2) three parameters, viz. oxidizability, electric conductivity and chloride content, can be adequately used to assess the quality of utilized wash water; 3) the composition of wash water is largely dependent on the health status of its users. PMID- 2891873 TI - Sequential study of vasculitis in MRL mice. AB - The frequency, age of onset and organ distribution of spontaneously occurring vasculitis was examined in a sequential study with 170 MRL mice of both substrains. Necrotizing vasculitis was seen in 55.8% of MRL/Mp-lpr/lpr mice studied, beginning at the age of 3 months. The kidney and urinary bladder were most frequently involved. In MRL/Mp- +/+ mice necrotizing vasculitis was much less frequently present (7.6%), beginning at the age of 18 months, and was seen only in the kidney, stomach and testes. In both substrains mononuclear infiltration of pulmonary vessel walls preceded the occurrence of necrotizing arteritis in other organs. The immunofluorescence study revealed the presence of immune complex components (immunoglobulin G, C3, murine leukaemia virus antigen gp71) in the vessel walls of the renal arteries of six out of 36 lpr/lpr mice with necrotizing arteritis. PMID- 2891874 TI - Immuno-gold localization of prion filaments in scrapie-infected hamster brains. AB - The brains of scrapie-infected hamsters have been examined for the presence of structures antigenically related to the prion protein (PrP 27-30). Glutaraldehyde perfused hamster brains, 72 days postinfection, were immunostained using rabbit monospecific antisera raised against synthetic peptides corresponding to the N terminal 13 or 15 amino acids of PrP 27-30, and using rabbit antisera raised against infectious prions or PrP 27-30 purified from scrapie-infected hamster brains. Antisera to the synthetic peptides stained extracellular filaments in agreement with previous immunoperoxidase studies which used affinity-purified PrP 27-30 antibodies; in addition to subependymal and subpial localization, we show ventricular and perivascular staining. Using a colloidal gold-secondary antibody technique, we have demonstrated that the antibodies labeled filaments measuring 7 to 17 nm in diameter. Whereas most of the periventricular and perivascular filaments appeared extracellular, some appeared to be within processes intimately associated with ependymal cells, degenerating membranes of astrocytes, and neurites. PMID- 2891876 TI - Testosterone, androstenedione, progesterone and 17 alpha-hydroxyprogesterone in plasma and testes of immature rats under basal conditions and after hCG stimulation. Effect of bilateral cryptorchidism. AB - Rats were made bilaterally cryptorchid at 21 days of age; sham-operated rats were used as controls. At 35 days, the animals were injected i.m. with saline or with 10 IU hCG. Progesterone, 17-hydroxyprogesterone, androstenedione and testosterone were measured in both testes and plasma under basal conditions and 2, 4, 8, 12, 24 and 72 h respectively after injection. The plasma levels and intratesticular contents of the steroids were generally lower in cryptorchid rats. The patterns of the steroid response to hCG were similar in both groups: in the testes and in the plasma, they increased acutely following hCG injection (except testicular androstenedione), then, after 72 h, returned to normal values in the plasma but remained higher than the basal values in the testes. These results suggest that there are no gross abnormalities in the testicular steroidogenic pathways and that the mechanism of action of hCG on the Leydig cells is unaltered in bilaterally cryptorchid immature rats. PMID- 2891877 TI - Gamma glutamyl transferase activity in rat colon during experimental colonic carcinogenesis. AB - Colonic gamma glutamyl transferase activity is raised in colonic malignancy. This study was undertaken to determine how early and how extensively this raised activity occurs during carcinogenesis. Sixty rats were given weekly injections of dimethylhydrazine for 16 weeks, and 20 rats acted as controls. Groups of treated and control rats were sacrificed at regular intervals during the pre-cancerous phase of carcinogenesis, and gamma glutamyl transferase activity was measured at several sites in the colon. Gamma glutamyl transferase activity was raised as early as 4 weeks after the first injection of dimethylhydrazine (p less than 0.05), and the elevation persisted until the development of overt tumours. The raised gamma glutamyl transferase activity was observed throughout both the proximal and distal colon long before the appearance of macroscopic tumours. We conclude that an early and widespread elevation of colonic gamma glutamyl transferase activity occurs during carcinogenesis. This may have useful applications in the early detection of colonic malignancy. PMID- 2891875 TI - Studies on the cellular localization and distribution of glucocorticoid receptor and estrogen receptor immunoreactivity in the central nervous system of the rat and their relationship to the monoaminergic and peptidergic neurons of the brain. AB - By means of monoclonal antibodies against the rat liver glucocorticoid receptor (GR) and the human estrogen receptor (ER), in combination with an immunocytochemical analysis, it has been possible to map out GR and ER immunoreactive (IR) neurons in the rat central nervous system and GR IR glial cells in the white matter. The GR IR is located in the cytoplasm and especially in the nucleus while the ER IR is only demonstrated in the nuclei of the neurons. Upon adrenalectomy the GR IR appears to be present exclusively in the cytoplasm, while after castration the ER IR is still exclusively present in the nuclei. Upon corticosterone treatment of the adrenalectomized rat the GR IR is again predominantly found in the nuclei of the neurons. These results indicate that the occupied GR and the unoccupied and occupied ER are located in the nuclei and the unoccupied GR in the cytoplasm. Evidence has been presented that large numbers of monoamine and peptide nerve cell bodies contain GR IR. Furthermore, neuronal GR IR is found in neuronal populations all over the central nervous system, especially in the cerebral cortex, the thalamus and the hypothalamus, indicating a major role of GR in regulating the metabolic and synaptic functions of the brain. The ER IR is instead limited to certain neuronal populations, mainly those of the preoptic area, the bed nucleus of the striae terminalis and the arcuate nucleus, suggesting a specific role in control of LHRH secretion and reproductive behaviour. PMID- 2891878 TI - The effect of nursing intervention on serum lipid level of patients taking beta blockers. PMID- 2891879 TI - Complete remission after autografting for chronic myeloid leukaemia. AB - A previously untreated 31-yr old female with Ph-positive chronic myeloid leukaemia (CML) received busulphan and melphalan at high dosage followed by an autograft of peripheral blood stem cells collected 4 weeks earlier. Though recovering haemopoiesis was at first mainly Ph-positive, Ph-negative haemopoiesis predominated at 12 months and has persisted until the most recent study (24 months post-autograft). Her haemopoietic cells now show no rearrangement of the bcr gene, unlike the cells collected at diagnosis. Autografting carried out soon after diagnosis could be valuable for obtaining cytogenetic remissions in other patients with CML. PMID- 2891880 TI - Acute pulmonary response to cotton bract extract in monkeys: lung function and effects of mediator modifying compounds. AB - It is well established that cotton dust inhalation can compromise lung function in textile workers. Challenges with a water-soluble extract of cotton bract (CBE) can also induce reversible airway obstruction in healthy volunteers. We have examined the effect of inhaled CBE in nonhuman primates and have attempted to inhibit the bronchoconstrictive response with mediator modifying compounds. CBE (34 mg/ml or 100 mg/ml) was administered via IPPB for 15 minutes (15 breaths/min) in 12 intubated, anesthetized, adult male monkeys (Macaca fascicularis). Breath by-breath determinations of pulmonary resistance, dynamic compliance (Cdyn), tidal volume, and breathing frequency were calculated from the transpulmonary pressure (esophageal balloon) and airflow signals and monitored for 2 hr postchallenge. Control challenges with distilled water were also performed in 3 monkeys with the greatest response from CBE. Five animals (42%) were found to respond to CBE with peak % changes in Cdyn greater than 45%. In 3 of these animals, we attempted to blunt the CBE response with chlorpheniramine (0.1 mg/kg i.v.) and a mast cell stabilizer lodoxamide (0.1 mg/ml aerosol). In these 3 animals the mean (+/- SD) peak % changes in Cdyn to CBE alone was -47.4 +/- 1.8. The CBE response following chlorpheneramine was -49 +/- 15.7 and following lodoxamide was -47.0 +/- 5.4. These data suggest that monkeys, like humans, can develop reproducible bronchoconstriction following an aerosol challenge with CBE. Furthermore, this bronchoconstriction in the monkey is probably not explained by the action of histamine or mediator release alone and an acute inflammatory reaction may be involved. PMID- 2891881 TI - Age-related changes of splenic T cells in mice--a flow cytometric analysis. AB - Splenic T cells of C57BL/6 mice, ranging in age from newborn to 24 months old, were examined by two-colour flow cytometry using monoclonal antibodies (moAbs) to Thy-1, Lyt-1, Lyt-2 and L3T4. Thy-1+ cells in the spleen increased gradually after the birth, and reached a plateau around at 3 months of age, but did not show a significant age-related decline even at 24 months of age. Lyt subpopulations of T cells (Lyt-1+2+, Lyt-1+2-, Lyt-1-2+) showed a proportional increase until 1 month of age, but the onset of their imbalance was observed as early as 3 months of age. The percentage of L3T4+ subpopulation stayed at a relatively constant level throughout life (approx. 55%). At the individual cell level, Lyt-2 antigen was most vulnerable to aging and its membrane surface density showed a prominent decrease in 24-month-old T cells. An apparent decline was observed in the mitogen reactivity and cell-mediated cytolytic T lymphocyte (CTL) activity of old T cells or their subpopulations which were purified by the cell sorter. PMID- 2891882 TI - The impact of echocardiographic results on treatment decisions for patients suspected of mitral valve prolapse. AB - Although echocardiography is frequently ordered in ambulatory settings for patients suspected of mitral valve prolapse (MVP), its impact on their subsequent management is unknown. We studied the relationship between the results of echocardiography for outpatients suspected of MVP, and two frequent medical decisions: treatment with beta blockers and the recommendation of antibiotic prophylaxis to prevent bacterial endocarditis. A medical record audit was performed on 274 outpatients referred to a university medical center echocardiography laboratory to rule out MVP. Although echocardiographic evidence for MVP significantly influenced the decision to recommend antibiotic prophylaxis (P less than 0.001), symptoms were more likely to be used as indications for beta blocker therapy in patients suspected of the condition. We conclude that echocardiographic results are used for recommending antibiotic prophylaxis to outpatients suspected of MVP, but not for beta-blocker therapy. PMID- 2891883 TI - [Diagnosis and treatment of schizophrenia]. PMID- 2891884 TI - [Renal insufficiency in rheumatoid arthritis. Effect of non-steroidal anti inflammatory agents]. PMID- 2891885 TI - The guinea-pig isolated atrium as a model system for the central actions of selected CNS stimulant and depressant drugs. Part 1: 3,3-Diakylglutarimide homologues and related drugs. AB - The 3H-noradrenaline pretreated, spontaneously beating, guinea-pig atrial preparation has been used as a model system to study the presynaptic and postsynaptic actions of selected drugs with stimulant (bemegride, pentylenetetrazol, picrotoxin, strychnine and 4-methyl-4-n-propylpiperidine hydrochloride), depressant (pentobarbitone, hydroxydione, trimethadione, 3-methyl 3-n-alkylglutarimide where alkyl = butyl, amyl or hexyl, 4-methyl-4-n propylpiperidone-2 hydrochloride, chlordiazepoxide and chlorpromazine) or dual stimulant-depressant (3-methyl-3-n-propylglutarimide and 5-ethyl-5-(1,3 dimethylbutyl) barbiturate and its (+) and (-) enantiomers) actions in the central nervous system of the mouse. 3H-Noradrenaline efflux and force and rate of atrial contraction were used as parameters of atrial function. With the exception of strychnine, picrotoxin and 4-methyl-4-n-propylpiperidine hydrochloride, which appear to act by different central mechanisms, there is good correspondence between the actions of the test drugs on the force of atrial contraction and in the CNS of the mouse. Thus, stimulant drugs increase and depressant drugs decrease the force of atrial contraction, while dual stimulant depressant drugs in low concentrations increase, and in higher concentrations, decrease the inotropic response. A similarly good correspondence generally exists between mouse and atrium with respect to the relative stimulant and depressant potencies of the test drugs, additive stimulation or depression for pairs of like acting drugs and 'analepsis' and 'anticonvulsant activity' for drugs with opposed central actions. No such relationships were found using tritium efflux or the chronotropic response as parameters of atrial function. Thus, the guinea-pig atrial preparation appears to be a good model system in which to demonstrate the acute CNS actions and interactions of the majority of the test drugs. Their positive and negative inotropic effects on the atrium have been explained in terms of a membrane phase distribution hypothesis of drug action, and their ability to facilitate or impede, respectively, the movement of Ca2/ across the atrial sarcolemmal membrane. It is proposed that these drugs may act by similar mechanisms at responsive sites in the brainstem reticular formation and related areas in the mouse. These may be primarily excitatory noradrenergic synapses integrated functionally with presynaptic or independent inhibitory GABAergic terminals. PMID- 2891887 TI - Renal deposition of cytomegalovirus antigen in immunoglobulin-A nephropathy. AB - Renal biopsy specimens from patients with various glomerular disorders were examined by indirect immunofluorescence microscopy with three different heterologous antibodies directed against cytomegalovirus and two heterologous antibodies against herpes simplex virus (HSV) type 1. All 31 samples from patients with immunoglobulin-A (IgA) nephropathy, 1 of 12 with systemic lupus erythematosus (SLE), and 1 of 5 with Henoch-Schonlein purpura (HSP) showed mesangial staining with cytomegalovirus antiserum, whereas no sample from 37 patients with other forms of glomerulonephritis was positive. Antigens of herpes simplex virus I were demonstrated in samples from 4 of 31 patients with IgA nephropathy, 1 of 12 patients with SLE, 1 of 5 patients with HSP, and 1 of 37 patients with other glomerular diseases. The consistent finding of glomerular cytomegalovirus antigen in IgA nephropathy suggests but does not prove that the virus has a role in the aetiology of this disorder. PMID- 2891886 TI - Difference between herpes simplex virus type 1 and type 2 neonatal encephalitis in neurological outcome. AB - 24 infants consecutively treated with acyclovir or vidarabine for neonatal herpes simplex virus (HSV) encephalitis were followed up for 6 months to 3 years to assess neurological and developmental outcome. 15 patients had HSV-2 and 9 had HSV-1 encephalitis. Infants with HSV-2 encephalitis presented with a higher frequency of seizures, greater pleocytosis and protein concentrations in the cerebrospinal fluid, and more frequent evidence of structural damage on computerised tomographic scans of the brain than did those with HSV-1 encephalitis. 1 patient died. All 9 HSV-1 patients were normal at follow-up (mean 19.4 months) compared with only 4 (23%) of the 14 surviving HSV-2 infected infants (p = 0.003). Among infants with HSV-2 encephalitis, 50% became microcephalic; 57% had seizure disorders; 64% had ophthalmological defects; 64% had cerebral palsy; and 57% had mental retardation. Infants with neonatal HSV-1 encephalitis treated with systemic antiviral chemotherapy have excellent neurological outcomes; the neurological morbidity of those with HSV-2 encephalitis is still high. PMID- 2891888 TI - TSH-receptor antibodies in mothers with Graves' disease and outcome in their offspring. AB - Blood was taken from 56 selected newborn babies whose mothers had Graves' disease, to assess the relation between their thyroid function and the presence of thyrotropin (TSH) binding inhibitor immunoglobulins (TBII) and thyroid stimulating antibodies (TSAb) in maternal serum. All the mothers of the thyrotoxic babies had both these TSH receptor antibodies in their serum. However, most of the mothers whose thyroid function had been well controlled in pregnancy gave birth to normal babies. 15 babies had a transient syndrome of low serum thyroxine (T4) and free T4 with normal TSH and this tended to be associated with TSH receptor antibodies in maternal serum (TBII 9/15, TSAb 4/15). 2 infants had transient hyperthyroxinaemia without hyperthyroidism and both their mothers showed strong TSAb activity without TBII activity. PMID- 2891889 TI - Chronic Ureaplasma urealyticum and Mycoplasma hominis infections of central nervous system in preterm infants. AB - In a prospective study of meningitis in 100 predominantly preterm infants, Ureaplasma urealyticum was isolated from the cerebrospinal fluid (CSF) of 8 and Mycoplasma hominis from the CSF of 5 babies undergoing investigation of suspected sepsis or treatment of hydrocephalus. U urealyticum was isolated from 6 infants with severe intraventricular haemorrhage and from 3 with hydrocephalus. In 4 babies multiple isolations were made over several weeks. There were clinical features of congenital infection with major neurological impairment in 1 infant infected with M hominis. Diagnosis is difficult because these organisms cannot be seen on gram stain and cannot readily be cultivated on routine bacteriological media, and CSF pleocytosis may be absent. This study, which used appropriate mycoplasmal media, shows that U urealyticum and M hominis are the most common microorganisms isolated from the CSF of newborn infants in a high-risk population. PMID- 2891891 TI - Pharmacological adaptive responses to drugs. PMID- 2891890 TI - Vasectomy and urolithiasis. AB - The relation between vasectomy and renal disease was examined in the data collection phase of a study of vasectomy and coronary artery disease. The date of onset and type of urological disease was obtained for 11,205 men enrolled in the US Coronary Artery Surgery Study. Urolithiasis was the most common reported urological disease. The relative risk for calculi in men who had had a vasectomy ranged from 2.6 for patients 30-35 years old to 1.3 for those aged 55-65. The age adjusted relative risk was 1.67 (p less than 0.001). PMID- 2891892 TI - Airflow limitation--reversible or irreversible. PMID- 2891893 TI - Dialysis arthropathy. PMID- 2891894 TI - Too many H2 antagonists. PMID- 2891895 TI - Measuring need for health care. PMID- 2891896 TI - Plastic devices: new fields for old microbes. PMID- 2891897 TI - AIDS and sex. PMID- 2891898 TI - Prevention and treatment of malaria. PMID- 2891899 TI - Duration of antimicrobial therapy for acute suppurative osteoarticular infections. AB - From 1974 to 1983, inclusive, 274 children with acute suppurative osteoarticular infections were treated with antibiotic regimens that were shorter than usually recommended. The median duration of antibiotic treatment for acute suppurative arthritis caused by staphylococci, streptococci, Haemophilus influenzae type b, gram-negative cocci, or other gram-negative bacteria was 23, 16, 16, 15, and 22 days, respectively. For acute osteomyelitis caused by staphylococci, streptococci, H influenzae, or other gram-negative bacteria the median duration of antibiotic therapy was 24, 23, 17, and 22.5 days, respectively. Osteoarthritis usually had to be treated for about a month. 180 patients received large dosages of oral antimicrobials after clinical stabilisation with intravenous treatment, the median duration of intravenous therapy being about a week (range up to 7 weeks). 99% of patients underwent needle aspiration for diagnostic reasons. 36%, 71%, and 63% of the patients with acute suppurative arthritis, osteomyelitis, and osteoarthritis, respectively, underwent incision and drainage. Recurrence occurred in 4 patients with acute osteomyelitis (3.8% of cases). There was no recurrence of arthritis. PMID- 2891900 TI - Painless lithotripsy: experience with 100 patients. AB - 123 patients underwent 320 extracorporeal shock wave lithotripsy (ESWL) sessions with the Wolf 'Piezolith 2200' lithotripter. The overall success rate, judged by adequate stone fragmentation into particles of 2 mm or less as seen on X-ray, was 92%. Few complications occurred. The lithotripter was easy to operate, and treatment was painless. PMID- 2891901 TI - The Swedish medical insurance schemes. The way ahead for the United Kingdom? PMID- 2891902 TI - Energy intake during pregnancy. PMID- 2891903 TI - Elimination of nicotine gum use. PMID- 2891904 TI - Forms of cocaine and psychiatric symptoms. PMID- 2891905 TI - Penicillin-resistant Borrelia encephalitis responding to cefotaxime. PMID- 2891907 TI - Privatised pharmacology at Oxford. PMID- 2891906 TI - Loss of bileducts after liver transplantation. PMID- 2891908 TI - Heart transplantation and preformed cytotoxic antibodies. PMID- 2891909 TI - Delayed clearance of HBsAG after transplantation for fulminant delta-hepatitis. PMID- 2891910 TI - Thyroglobulin level helps to predict recurrence after lobo-isthmusectomy in patients with differentiated thyroid carcinoma. PMID- 2891911 TI - Hyperphosphataemia in haemolysis. PMID- 2891912 TI - Reduction of HBV infections and mass immunisation. PMID- 2891913 TI - Intracavernosal pharmacotherapy with injection pen. PMID- 2891914 TI - Penicillin-resistant Neisseria meningitidis in southern Africa. PMID- 2891915 TI - Dimethylformamide and testicular cancer. PMID- 2891916 TI - Immunosuppressive effects of dioxin in the development of Kaposi's sarcoma and non-Hodgkin's lymphoma. PMID- 2891917 TI - New mode of action for lactulose. PMID- 2891919 TI - Campylobacter pylori and pernicious anaemia. PMID- 2891918 TI - Antibodies to plasmid-encoded proteins of enteropathogenic Yersinia in patients with autoimmune thyroid disease. PMID- 2891920 TI - Coeliac disease and Holy Communion. PMID- 2891921 TI - Vancomycin-resistant enterococci. PMID- 2891922 TI - Sporadic non-A, non-B hepatitis. PMID- 2891923 TI - HLA DQ Polymorphism in rheumatoid arthritis. PMID- 2891926 TI - NHS in crisis. PMID- 2891924 TI - Aseptic meningitis from over-the-counter ibuprofen. PMID- 2891927 TI - Magnetic resonance scanners. PMID- 2891925 TI - Evaluation of a bedside analyser. PMID- 2891928 TI - Cruelty in an old people's home. PMID- 2891929 TI - Screening multiple endocrine neoplasia type 2A families using DNA markers. PMID- 2891930 TI - Barrett's oesophagus and colonic cancer. PMID- 2891931 TI - DNA homology between a novel human herpesvirus (HHV-6) and human cytomegalovirus. PMID- 2891932 TI - Shortsighted children. PMID- 2891934 TI - HIV and the pancreas. PMID- 2891933 TI - HIV transmission from female to male at improperly protected sexual intercourse. PMID- 2891935 TI - Declining prevalence of Kaposi's sarcoma in homosexual AIDS patients paralleled by fall in cytomegalovirus transmission. PMID- 2891936 TI - Tattooing in prison and HIV infection. PMID- 2891937 TI - Atenolol in irritable bowel syndrome. PMID- 2891938 TI - AIDS and medical ethics. PMID- 2891939 TI - Midazolam in terminal care. PMID- 2891940 TI - Mexiletine for treatment of chronic painful diabetic neuropathy. AB - Sixteen of nineteen patients completed a randomised double-blind crossover trial to assess the effect of oral mexiletine (10 mg/kg bodyweight daily) on the symptoms and signs of chronic painful diabetic neuropathy. The median age of the sixteen patients was 50 years (range 30-64). Assessment with a five-item clinical symptom scale showed significant improvement during the mexiletine phase compared with the placebo phase. Pain was reduced during mexiletine but not during placebo, as assessed by a visual analogue rating scale. Mexiletine treatment had no effect on tendon reflexes, vibration threshold levels, beat-to-beat variation in heart rate during deep breathing, and postural blood pressure response. Mild side-effects were seen in three of the sixteen patients during mexiletine treatment. PMID- 2891941 TI - Staphylococcal sepsis. The changing pattern of disease and therapy. PMID- 2891942 TI - Therapeutic trials in coronary thrombosis should measure left ventricular function as primary end-point of treatment. AB - Clinical trials in coronary thrombosis can record as end-points either death or an index of left ventricular function (ejection fraction or end-systolic volume) which can be used as a surrogate for long-term mortality. Hospital mortality for patients under 70 years of age in whom effective thrombolysis is achieved should now be no more than about 5%. To show a 20% reduction (to 4%) in mortality with an alpha error (two-sided) of 0.05 and a beta error of 0.2 requires 15,000 patients. By contrast, a 25% improvement towards normal in ejection fraction (from about 59% to about 62%) requires only 384 patients. Since it is likely that one of several thrombolytic agents will be effective in conjunction with one or more myocardial protective agents, many trials will be required, and it may be more appropriate in future studies to measure left ventricular function rather than mortality as the principal end-point. PMID- 2891943 TI - Should physicians withhold life-sustaining care from patients who are not terminally ill? PMID- 2891944 TI - Selective histopathology of appendicectomy specimens. PMID- 2891945 TI - Total body water and very-low-calorie diets. PMID- 2891946 TI - Urogastrone/epidermal growth factor in treatment of congenital microvillous atrophy. PMID- 2891947 TI - "Botryoid nuclei" of leucocytes in the haemorrhagic shock and encephalopathy syndrome. PMID- 2891948 TI - Mitozantrone-induced onycholysis. PMID- 2891949 TI - What do newly appointed rheumatologists think? PMID- 2891950 TI - Cavitation and arterial blood flow. PMID- 2891951 TI - Biogenic amine adducts, monoamine oxidase inhibitors, and smoking. PMID- 2891952 TI - Growth retardation in asthmatic children treated with inhaled beclomethasone dipropionate. PMID- 2891953 TI - Low-frequency vibration in application of bone cement. PMID- 2891954 TI - Successful treatment with thalidomide of acute graft-versus-host disease after bone-marrow transplantation. PMID- 2891955 TI - Marrow donors and international cooperation. PMID- 2891956 TI - Campylobacter pylori and duodenogastric reflux in peptic ulcer disease and gastritis. PMID- 2891957 TI - Campylobacter pylori and development of duodenal ulcer. PMID- 2891958 TI - Diet, ulcer disease, and fish oil. PMID- 2891959 TI - Traumatic corneal abrasion. PMID- 2891960 TI - HIV-2 in Britain: no evidence, yet. PMID- 2891961 TI - Benzodiazepine prescribing. PMID- 2891962 TI - Fibrinogen and carboxyhaemoglobin in peripheral arterial disease. PMID- 2891963 TI - Minimal dose (1.25 micrograms) hepatitis B vaccine for infants and newborn babies, 4 years later. PMID- 2891964 TI - Nutritional dialogue: a lesson from Francophone Africa. PMID- 2891965 TI - Lot quality assurance sampling in health monitoring. PMID- 2891966 TI - Gaza's health services. PMID- 2891967 TI - Management of clinical trials. PMID- 2891968 TI - Running amok. PMID- 2891969 TI - Radionuclide imaging of scrotum. PMID- 2891970 TI - Antipaternal lymphocytotoxic antibodies in pregnancy. PMID- 2891971 TI - Myalgic encephalomyelitis and alpha-interferon. PMID- 2891972 TI - Improving the efficiency of drug administration with jet nebulisers. PMID- 2891973 TI - Coeliac disease as cause of protracted diarrhoea in Indian children. PMID- 2891974 TI - Longstanding infection with Schistosoma mansoni. PMID- 2891975 TI - Psychiatric day hospitals. PMID- 2891976 TI - H2-receptor antagonist non-responders. PMID- 2891977 TI - Comparison of continuous arteriovenous haemofiltration and haemodialysis in acute renal failure. PMID- 2891978 TI - Detection of pyrogen by cytokine release. PMID- 2891979 TI - Has your sister had her smear test? PMID- 2891980 TI - Oronasal obstruction, lung volumes, and arterial oxygenation. AB - The effects were studied on lung volumes of partial (chronic) nasal obstruction, total overnight nasal occlusion with a nasal pack, and interdental wiring for 6-8 weeks. Total lung capacity, functional residual capacity, and residual volume decreased significantly with total nasal occlusion and with surgical relief of chronic nasal obstruction. All three volumes increased with interdental wiring. It is concluded that these effects are a result of changes in oronasal resistance: lung volume is enlarged by an overall increase in resistance and diminished by a decrease in resistance. These findings imply that the resistance to expiration provided by the nose helps maintain lung volumes and so may indirectly determine arterial oxygenation. PMID- 2891981 TI - Phase I studies of 2',3'-dideoxycytidine in severe human immunodeficiency virus infection as a single agent and alternating with zidovudine (AZT). AB - Five dose regimens of 2',3'-dideoxycytidine (ddC) were administered, intravenously for 2 weeks then orally for 4 or more weeks, to 20 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). ddC was well absorbed from the gut and crossed the blood-brain barrier. 10 of the 15 patients who received 0.03-0.09 mg/kg every 4 h had increases in their absolute number of T4+ T cells at week 2 (p less than 0.05), though in many these rises were not sustained. 11 of 13 evaluable patients had a fall in their serum human immunodeficiency virus (HIV)p24 antigen by week 2 of therapy (p less than 0.01); in 4 patients the p24 antigen subsequently rose to baseline while in others the decline was sustained. Dose-related toxic effects included cutaneous eruptions, fever, mouth sores, thrombocytopenia, and neutropenia. A reversible painful peripheral neuropathy developed in 10 patients after 6-14 weeks' treatment. These results suggest that ddC has activity against HIV in vivo and has a different toxicity profile from that of zidovudine (AZT). 6 patients with AIDS or ARC were given an alternating regimen of oral AZT (200 mg every 4 h for 7 days) and oral ddC (0.03 mg/kg every 4 h for 7 days). The regimen was well tolerated, and the 5 patients who completed 9 or more weeks of treatment had sustained rises in their T4+ T cells and/or falls in p24 antigen. PMID- 2891982 TI - Identification of an intestinal immune response using peripheral blood lymphocytes. AB - The intestinal immune response of volunteers given the oral vaccine Salmonella typhi Ty21a was assessed with a new immunoassay which measures specific antibody secretion by peripheral blood lymphocytes (PBL). Peak IgA, IgG, and IgM production by PBL occurred on day 7 after the start of vaccination. Peak antibody secretion by PBL occurred several days earlier than the serum antibody peak. All volunteers showed a specific PBL antibody response, but serum or intestinal immune responses, when demonstrable, were highly variable. Peak PBL IgA antibody response correlated with degree of rise in IgA antibody in serum (p = 0.00098) and the intestinal fluid (p = 0.0024). The assay is a useful means of measuring humoral immune response at a mucosal surface after local administration of antigen. PMID- 2891983 TI - Helmet-induced skull base fracture in a motorcyclist. AB - Observations after a fatal motorcycle accident suggested that the face bar of a full-face helmet may transmit an impacting force to the skull base via the chin strap and the mandibular rami and condyles, bypassing the energy-absorbing facial bones. If this mechanism is confirmed, the structural properties of these face bars will need to be reassessed. PMID- 2891984 TI - Dominant inheritance of atopic immunoglobulin-E responsiveness. AB - The familial occurrence of atopy, defined by skin prick test responses and serum immunoglobulin-E (IgE) titres to common inhaled allergens, was studied in 239 members of 40 nuclear and 3 extended families. 90% of the atopic children in the nuclear families had at least one demonstrably atopic parent. In each extended family, atopy was vertically transmitted, and 31 of 47 (66%) offspring of marriages between atopic and unaffected parents were atopic. Of the designated atopic subjects, 83% admitted to symptoms suggesting atopic disease but only 30% regarded themselves as having any such disorder. It is suggested that atopy, the propensity to produce IgE in response to common, usually inhaled, allergens, is inherited as an autosomal dominant character but that its clinical expression depends on interaction with other factors. PMID- 2891985 TI - The Abortion Act twenty years on. PMID- 2891987 TI - Measuring the PTH level. PMID- 2891988 TI - Conferences in perspective. PMID- 2891986 TI - Molecular mechanisms in familial and sporadic cancers. PMID- 2891990 TI - Hypertension, blood viscosity, and cardiovascular morbidity in renal failure: implications of erythropoietin therapy. AB - Recombinant human erythropoietin is a major advance in the management of patients with chronic renal failure. The sustained dose-dependent rise in haematocrit which it produces effectively abolishes symptoms of anaemia, but at the cost of an increase in blood viscosity. This in turn predisposes to increased vascular resistance and the development of hypertension. Over half of all deaths of patients with end-stage renal failure are from cardiovascular disease, notably myocardial infarction, heart failure, and stroke, for which hypertension is a known risk factor. Erythropoietin-related increases in blood pressure are therefore of particular concern, and seem to be most severe in previously hypertensive patients. There is now a need to establish the optimum rate and extent of rise of haematocrit required to alleviate symptoms without incurring undue risk. PMID- 2891989 TI - Properdin deficiency. PMID- 2891991 TI - Induction of therapeutic abortion in early pregnancy with mifepristone in combination with prostaglandin pessary. AB - Therapeutic abortion was induced in 100 women in early pregnancy (less than 56 days' amenorrhoea) with a combination of the antigestagen mifepristone (RU 486) and a synthetic prostaglandin analogue, gemeprost. Mifepristone in oral doses of 400-600 mg was followed 48 h later by a gemeprost vaginal pessary (0.5-1.0 mg). Bleeding was induced in all women 22-70 h after the mifepristone dose and although bleeding continued for 4-43 days (median 12) the total measured blood loss was only a median of 72.5 ml (range 15-398). Complete abortion occurred in 95 women. Surgical evacuation of the uterus for minimum debris was required in the remaining 5. Only 10 women had diarrhoea or pain that required opioid analgesia. The combination of mifepristone and gemeprost provides a safe and effective alternative to surgical evacuation of the uterus for therapeutic abortion in early pregnancy. PMID- 2891993 TI - Immunoreactive alpha-interferon in insulin-secreting beta cells in type 1 diabetes mellitus. AB - Of 37 pancreases removed at necropsy from patients with type 1 diabetes 34 had residual beta cells. In 33 of the 34 the beta cells were positive for immunoreactive alpha-interferon, and this finding in islets was related to hyperexpression of class I major histocompatibility complex (MHC) antigens. Of islets showing class I hyperexpression 93% contained alpha-interferon compared with 0.4% of those showing no hyperexpression. Among 80 control pancreases significant numbers of beta cells containing alpha-interferon were present only in 4 cases of acute infantile viral pancreatitis, known to be caused by Coxsackie B viral infection in 3 cases. Chronic viral infection of beta cells may underlie the pathogenesis of some cases of type 1 diabetes. PMID- 2891992 TI - Controlled trial of prednisolone as adjuvant in treatment of tuberculous constrictive pericarditis in Transkei. AB - In Transkei, 143 patients with active tuberculous constrictive pericarditis without significant pericardial effusion all received the same daily 6-month antituberculosis regimen of streptomycin, isoniazid, rifampicin, and pyrazinamide for 14 weeks followed by isoniazid and rifampicin. They were randomly allocated to receive in addition either prednisolone or placebo for the first 11 weeks; the comparison was double-blind throughout treatment and follow-up. In the 114 patients assessable up to 24 months, improvement was significantly more rapid in the prednisolone group, as shown by the rate of fall in the mean pulse rate and the rate at which jugular venous pressure and level of physical activity became normal. During follow-up, 2 (4%) of the 53 prednisolone and 7 (11%) of the 61 placebo patients died from pericarditis, and 11 (21%) and 18 (30%), respectively, required pericardiectomy. By 24 months 50 (94%) prednisolone and 52 (85%) placebo patients had a favourable status. 3 patients (1 prednisolone, 2 placebo) were normally active but were classified as not having achieved a favourable status. It is recommended that, in the absence of a specific contraindication, antituberculosis chemotherapy should be initially supplemented by steroids. PMID- 2891994 TI - Impairment of ventilatory function and pulmonary gas exchange in non-smoking coalminers. AB - Indices of ventilatory function and pulmonary gas exchange in 32 non-smoking coalminers (mean age 38.1) were compared with those of 34 non-smoking steelworkers of similar age. The coalminers had significantly lower forced expiratory volume in 1 s (FEV1) and maximum expiratory flow rates and significantly higher residual volume, but similar vital capacity and indices derived from the single-breath test. Pulmonary diffusing capacity for CO and indices of CO2 exchange were similar in both groups. Arterial partial pressure of O2 (PaO2) was significantly lower and alveolar-arterial O2 difference was significantly higher in coalminers than in controls, both at rest and during exercise. There was no relation between lung function and radiological signs of simple pneumoconiosis (10 coalminers had pneumoconiosis). The differences in FEV1 (0.42 l) and in PaO2 (10 mm Hg) between the two groups are the same or larger than those usually found between smokers and non-smokers. Exposure to coaldust may result in biologically significant alterations of lung function even in the absence of pneumoconiosis. PMID- 2891995 TI - Difluoromethylornithine for arseno-resistant Trypanosoma brucei gambiense sleeping sickness. AB - 26 patients with arseno-resistant Trypanosoma brucei gambiense trypanosomiasis were treated with difluoromethylornithine (eflornithine), an inhibitor of ornithine decarboxylase, given intravenously, then orally. There was rapid disappearance of trypanosomes in the cerebrospinal fluid (CSF), gradual decrease of CSF lymphocytosis, and parallel improvement in central nervous system status. Side-effects, including diarrhoea, anaemia, and hair loss, were common but tolerable and reversible. 5 patients died during or shortly after treatment. None of the 21 patients who completed therapy has had a relapse during the 6-30 month follow-up. PMID- 2891996 TI - Megakaryocytes and platelet clumps as the cause of finger clubbing. AB - There is now strong evidence that megakaryocytes continually emerge from the bone marrow but are trapped by the pulmonary capillary bed and fragment there into platelets. It is suggested that in disorders in which megakaryocytes or megakaryocyte fragments bypass the lung capillary network (eg, right-to-left intracardiac shunts, carcinoma of the bronchus), or in which large platelet clumps form on the left side of the heart or in large arteries (eg, subacute bacterial endocarditis, subclavian aneurysm), or in which there tends to be a chronic platelet excess (eg, chronic inflammatory bowel disease), these large particles may reach the fingertips in axial vascular streams and impact there, releasing platelet-derived growth factor. This material is known to cause increased capillary permeability and connective tissue hypertrophy. It is suggested that this mechanism is the cause of clubbing of the fingers. PMID- 2891997 TI - Unravelling HUS. PMID- 2891998 TI - Privatised pharmacology. PMID- 2891999 TI - Re-stenosis following angioplasty. PMID- 2892000 TI - Suppression of adrenal androgens. PMID- 2892001 TI - Death of a journal. PMID- 2892002 TI - The pathogenesis of humoral hypercalcaemia of malignancy. AB - The syndrome of humoral hypercalcaemia of malignancy (HHM) is characterised by end-organ manifestations of parathyroid-hormone (PTH)-like effects such as abnormalities of renal tubular calcium and phosphate transport, increased nephrogenous cyclic AMP and 1,25 dihydroxyvitamin D production, and increased osteoclastic bone resorption. Despite this, true ectopic PTH production has seldom been documented in HHM. A number of bone-resorbing factors, including prostaglandins, prostaglandin-stimulating factors, lymphokines, growth factors, and vitamin-D-like sterols, have been implicated as causes of HHM, but none can reproduce the PTH-like biochemical features characteristic of the syndrome. PTH related peptides have recently been isolated from tumours associated with HHM. These substances are the most likely putative humoral mediators of HHM, since they are structurally similar to PTH in the aminoterminal region and interact with the PTH receptor in vitro. However, the remainder of the molecule is quite distinct from PTH, which accounts for the absence of PTH immunoreactivity in serum and tumour extracts from HHM patients. Since these factors seem to act by binding to the PTH receptor, synthetic PTH antagonists may in the future be a means of treating HHM. PMID- 2892003 TI - Treatment of lower respiratory infections. PMID- 2892004 TI - The old, the very old, and the too old. PMID- 2892005 TI - Protection for the ozone shield. PMID- 2892006 TI - Diagnosing sexual abuse. PMID- 2892007 TI - Absence of allergic reaction to cyclosporin capsules in patient allergic to standard oral and intravenous solution of cyclosporin. PMID- 2892008 TI - Ophthalmic use of chloramphenicol. PMID- 2892009 TI - Selective histopathology for appendix specimens. PMID- 2892011 TI - Tamoxifen. PMID- 2892012 TI - Interpreting prolactin levels. PMID- 2892013 TI - Paternal hydrocarbon exposure in Prader-Willi syndrome. PMID- 2892010 TI - "Intermediate" doses of tamoxifen in progressive advanced breast-cancer. PMID- 2892014 TI - Potency of oral morphine. PMID- 2892015 TI - Thrombolysis at home. PMID- 2892016 TI - Paternal leucocyte injections in recurrent spontaneous abortion. PMID- 2892017 TI - Immune mechanisms and pre-eclampsia. PMID- 2892018 TI - Acyclovir-resistant herpes simplex virus infection due to altered DNA polymerase. PMID- 2892019 TI - Monoclonal anti-CD4 in arthritis. PMID- 2892021 TI - Role of the pharmaceutical industry in major clinical trials. PMID- 2892020 TI - Cycad use and motor neurone disease in Kii peninsula of Japan. PMID- 2892022 TI - Alcohol abuse. PMID- 2892023 TI - Psychiatric day-hospitals. PMID- 2892024 TI - Who needs a college for obstetrics and gynaecology? PMID- 2892025 TI - Paediatric intensive care units. PMID- 2892026 TI - Differentiation of uric acid from dihydroxyadenine stones. PMID- 2892027 TI - Parvovirus B19 associated with pseudoappendicitis. PMID- 2892028 TI - Hypergastrinaemia after long-term H2-blocker treatment. PMID- 2892029 TI - Omeprazole. PMID- 2892030 TI - Bismuth/ofloxacin combination for duodenal ulcer. PMID- 2892031 TI - Famotidine does not have a negative inotropic effect. PMID- 2892032 TI - Lithotripsy of gallstones. PMID- 2892033 TI - Progression to AIDS in homosexual men co-infected with HIV and HTLV-I in Trinidad. PMID- 2892034 TI - Treatment of HIV-induced retinoid-resistant psoriasis with zidovudine. PMID- 2892035 TI - Violence and solvents. PMID- 2892036 TI - Rates of violent crime from hospital records. PMID- 2892037 TI - Are children with lymphoblastic leukaemia resistant to 6-mercaptopurine because of 5'-nucleotidase? PMID- 2892038 TI - 6-Mercaptopurine and antiviral nucleoside analogues. PMID- 2892039 TI - Cost of cyclosporin. PMID- 2892040 TI - Mupirocin-resistant Staphylococcus aureus. PMID- 2892041 TI - Dysgonic fermenter organisms and post-splenectomy risks. PMID- 2892042 TI - Resistance to beta-lactam/clavulanate. PMID- 2892043 TI - Lead foil on wine bottles. PMID- 2892044 TI - Death of an epileptic patient in a prison medical wing. PMID- 2892045 TI - Informed consent: a Canadian case in a British perspective. PMID- 2892046 TI - Crisis in the NHS: Downing Street on the counterattack after the presidents' statement. PMID- 2892047 TI - 1-Year controlled randomised trial of prevention of early postmenopausal bone loss by intranasal calcitonin. AB - 79 women who had been menopausal for less than 36 months and who had not received any form of treatment to prevent bone loss were randomly assigned to a 12-month regimen of calcium 500 mg/day or calcium 500 mg plus intranasal salmon calcitonin 50 IU/day for 5 days per week. After 12 months of treatment bone mineral density had decreased in the calcium-only group by a mean of 3.16 (SEM 0.6)% (p less than 0.01) but had increased in the calcium plus calcitonin group by 1.38 (0.8)% (NS). The difference in response between the two treatment groups was also highly significant (p less than 0.01), as was the difference between values for hydroxyprolinuria/creatininuria (p less than 0.01). Endogenous calcitonin levels rose significantly in the calcium group but remained unchanged in calcitonin treated patients. Treatment by calcitonin and calcium was not followed by increased secretion of parathyroid hormone. The findings suggest that intranasal calcitonin can counteract early postmenopausal bone loss. PMID- 2892048 TI - Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. AB - The association between level of cannabis consumption and development of schizophrenia during a 15-year follow-up was studied in a cohort of 45,570 Swedish conscripts. The relative risk for schizophrenia among high consumers of cannabis (use on more than fifty occasions) was 6.0 (95% confidence interval 4.0 8.9) compared with non-users. Persistence of the association after allowance for other psychiatric illness and social background indicated that cannabis is an independent risk factor for schizophrenia. PMID- 2892050 TI - Detection of Chlamydia trachomatis by enzyme immunoassay in patients with trachoma. AB - Trachoma control necessitates identification of individuals shedding ocular chlamydiae. Conventional techniques of chlamydial culture are unsuitable for large field surveys in developing countries. In this study an enzyme immunoassay (EIA) developed for the detection of chlamydial antigen in genital-tract infection was used in trachoma. Conjunctival swabs were taken for chlamydial antigen detection from 1225 subjects in a Gambian village with endemic trachoma. Of these, 997 had insignificant or no disease and 172 had mild, 30 moderate, and 26 severe disease. Chlamydial antigen was detected in 5.0%, 20.3%, 46.7%, and 26.9% of subjects in these four categories, respectively. Samples for chlamydial isolation were obtained from 259 subjects. The corresponding rates of detection obtained by chlamydial isolation were 3/90 (3.3%), 16/129 (12.4%), 7/21 (33.3%), and 7/19 (36.8%). If isolation is taken as the "gold standard", the EIA technique had a sensitivity of 70.6% and a specificity of 90%. A substantial proportion of subjects with severe conjunctival scarring, from whom chlamydiae cannot generally be isolated, were antigen positive by EIA, implying that persistent chlamydial antigen plays a part in the pathogenesis of the late sequelae of trachoma. PMID- 2892049 TI - Reduced B-cell galactosyltransferase activity in rheumatoid arthritis. AB - Autosensitisation to IgG may be important in the pathogenesis of rheumatoid arthritis and could be related to reduced glycosylation of the oligosaccharides in the C gamma 2 region of serum IgG. The activity of galactosyltransferase, the enzyme that catalyses the addition of galactose to the oligosaccharide chains, was measured in the circulating B cells of seventeen patients with classic rheumatoid arthritis. It was significantly lower than that of a group of eleven controls (p less than 0.001) or of nine age-matched controls (p less than 0.001). In contrast, the enzyme activity of the T cells was within the range of that in nine age-matched controls, and enzyme activity in monocyte-rich mononuclear-cell populations was higher than in controls, possibly reflecting stimulation of the monocytes in rheumatoid arthritis. These findings suggest that galactosyltransferase may regulate the degree of glycosylation during IgG synthesis and could therefore be implicated in the rheumatoid inflammatory process. PMID- 2892051 TI - Evidence for involvement of hypocapnia and hypoperfusion in aetiology of neurological deficit after cardiopulmonary bypass. AB - Arterial and jugular bulb pressures and blood gas tensions were recorded for later analysis in 65 patients having coronary artery graft surgery. In the first 35 (group A) routine peroperative monitoring was used; and in the next 30 (group B), similar in age and other characteristics, special measures were adopted to maintain normocapnia (PaCO2 35-45 mm Hg) by continuous monitoring during surgery. On the third postoperative day clinical neurological deficits were observed in 46% of group A and 27% of group B, and psychometric deficits in 71% and 40%, respectively. On analysis of the records, more than half of group A proved to have been hypocapnic immediately before onset of cardiopulmonary bypass, and those with postoperative deficits differed from the others in this group in having had greater changes in PaCO2 after onset of bypass and lower cerebral perfusion pressures in the first 10 minutes of bypass, usually because of a rise in cerebral venous pressure. PMID- 2892052 TI - Pancreatic abnormalities in type 2 diabetes mellitus. PMID- 2892053 TI - Computer measurements of coronary artery disease. PMID- 2892054 TI - Chasing rainbows no more: damage limitation at the MRC. PMID- 2892055 TI - Herpes gestationis and placental antigens. PMID- 2892056 TI - Saving the NHS: let the petitions continue. PMID- 2892057 TI - The Drones Club. PMID- 2892058 TI - Treatable aspects of infection due to human immunodeficiency virus. PMID- 2892059 TI - Severity of illness: concepts and measurements. PMID- 2892060 TI - From Laveran's discovery to DNA probes: new trends in diagnosis of malaria. PMID- 2892062 TI - A long-discontinued practice. PMID- 2892061 TI - Hogarth and hospitals. PMID- 2892063 TI - Time saved, for what? PMID- 2892064 TI - Think horses, not zebras. PMID- 2892065 TI - Colchicine for recurrent pericarditis. PMID- 2892066 TI - Toxic effects after laser decomposition of intraocular gases. PMID- 2892067 TI - Segmental necrotising jejunitis. PMID- 2892068 TI - Proprofol and the electroencephalogram. PMID- 2892069 TI - Sodium valproate, pregnancy, and infantile fatal liver failure. PMID- 2892071 TI - Quinolone/ureidopenicillin cross-resistance in gram-negative bacteria. PMID- 2892070 TI - Successful treatment of relapsing Clostridium difficile colitis with Lactobacillus GG. PMID- 2892072 TI - Eradication of smallpox virus stocks. PMID- 2892073 TI - Treatment of Langerhans cell histiocytosis with alpha-interferon. PMID- 2892074 TI - Anti-IFN-alpha titres during interferon therapy. PMID- 2892075 TI - Acute leukaemia during pregnancy. PMID- 2892076 TI - Immunodeficiency, immunity, and staphylococcal infection. PMID- 2892077 TI - Reversal by intradermal hepatitis B vaccination of unresponsiveness to HBsAg. PMID- 2892078 TI - Transient leucopenia induced by granulocyte-macrophage colony-stimulating factor. PMID- 2892079 TI - Reduction of ectopic pregnancy by ultrasound methods. PMID- 2892080 TI - Alpha-interferon in primary idiopathic myelofibrosis. PMID- 2892081 TI - Hyperkalaemia and spironolactone. PMID- 2892082 TI - Retinoids and malignancy. PMID- 2892083 TI - Carbenoxolone and hypokalaemia. PMID- 2892084 TI - Angiotensin-converting enzyme inhibitors and cough. PMID- 2892085 TI - Oral contraceptives and breast cancer. PMID- 2892086 TI - Diagnosis of ascites by auscultatory percussion and hand-held ultrasound unit. PMID- 2892088 TI - Charges for preventive services: what difference will it make? PMID- 2892087 TI - HTLV-I antibodies and lymphoproliferative disease of granular lymphocytes. PMID- 2892089 TI - Does social work work? PMID- 2892090 TI - Science in court. PMID- 2892091 TI - Health for all targets. PMID- 2892092 TI - Closure of dependence units. PMID- 2892093 TI - HIV testing of pregnant women. PMID- 2892094 TI - Low-dose oral interferon in patient with AIDS. PMID- 2892095 TI - Testing for neurological involvement in HIV infection. PMID- 2892096 TI - Pseudautosomal locus for psychosis? PMID- 2892097 TI - Laser surgery of the oesophagus. PMID- 2892098 TI - Lignocaine-prilocaine cream for lumbar puncture. PMID- 2892100 TI - Stump carcinoma after Billroth I resections. PMID- 2892099 TI - Somatostatin and irritable bowel syndrome. PMID- 2892101 TI - Managing dyspepsia. PMID- 2892102 TI - [Important progress in the genetics of developmental processes]. PMID- 2892103 TI - Benzodiazepine receptor and neurotransmitter studies in the brain of suicides. AB - The characteristics of benzodiazepine binding sites (affinity, number heterogeneity) were studied on frozen sections of hippocampus of 7 suicides and 5 controls subjects, using biochemical and autoradiographic techniques. 3H flunitrazepam was used as ligand, clonazepam and CL 218,872 as displacing agents. Some neurotransmitters or their derivatives (GABA, catecholamines, hydroxy indols) were evaluated quantitatively in parallel in the hippocampal tissue by liquid chromatography. We observed mainly an increase in the Ki of CL 218,872 subtype I binding sites in suicides, (7.48 +/- 1.7 to 17.24 +/- 1.7 nM, P less than 0.01), (m +/- SEM) and an increase in % of type I binding sites (30 +/- 4.2 to 42 +/- 2.5, P = 0.01). Among neurotransmitters, only norepinephrine differed significantly between controls and suicides (11.34 +/- 1.9 to 24.34 ng/g tissue, P = 0.02). PMID- 2892104 TI - Pharmacological characterisation of the dopamine-sensitive adenylate cyclase in cockroach brain: evidence for a distinct dopamine receptor. AB - Dopamine increases cyclic AMP production in crude membrane preparations of cockroach brain with plateaus in cyclic AMP production occurring between 1-10 microM and at 10 mM. Maximal production of cyclic AMP is 2.25 fold greater than that of control values. Octopamine also increases cyclic AMP production with a Ka of 1.4 microM and maximal production 3.5 fold greater than that of control. 5 Hydroxytryptamine does not increase cyclic AMP production. The effects of octopamine and dopamine are fully additive. The vertebrate dopamine agonists ADTN and epinine stimulate the dopamine-sensitive adenylate cyclase (AC) with Ka values of 4.5 and 0.6 microM respectively and with maximal effectiveness 1.7 fold greater than that of control. The selective D2-dopamine agonist LY-171555 stimulates cyclic AMP production to a similar extent with a Ka of 50 microM. Other dopamine agonists (apomorphine, SKF-82526, SKF-38393) have no stimulatory effects. The octopamine-sensitive AC is inhibited by a variety of antagonists known to affect octopamine and dopamine receptors, with the following order of potency: mianserin greater than phentolamine greater than cyproheptadine greater than piflutixol greater than cis-flupentixol greater than SCH-23390 greater than (+)-butaclamol greater than SKF-83566 greater than SCH-23388 greater than sulpiride greater than spiperone greater than haloperidol. The dopamine-sensitive AC is inhibited by the same compounds with the following order of potency: piflutixol greater than cis-flupentixol greater than (+)-butaclamol greater than spiperone greater than or equal to SCH-23390 greater than cyproheptadine greater than SKF-83566 greater than SCH 23388 greater than mianserin greater than phentolamine greater than sulpiride greater than haloperidol. With the exception of mianserin, 3H-piflutixol is displaced from brain membranes by dopamine antagonists with an order of potency similar to that observed for the inhibition of dopamine-sensitive AC. The results indicate that the octopamine- and dopamine sensitive AC in cockroach brain can be distinguished pharmacologically and the dopamine receptors coupled to AC have pharmacological characteristics distinct from vertebrate D1- and D2-dopamine receptors. PMID- 2892105 TI - An evaluation of intravenous, subcutaneous, and in vitro activity of new agmatine analogs of growth hormone-releasing hormone hGH-RH (1-29)NH2. AB - The effects of new Agmatine (Agm) analogs of human growth hormone-releasing hormone (GH-RH) were compared to GH-RH (1-29)NH2 and to (D-Ala2)GH-RH(1-29)NH2 after intravenous (IV) and subcutaneous (SC) administration to pentobarbital anesthetised male rats and in vitro using superfused rat pituitary cell system. After IV administration, the analogs: (D-MeAla2,Nle27)GH-RH(1-28)Agm(JG-75), (desamino-Tyr1,D-Ala2,Nle27)GH-RH(1-28)Agm(JG-77), (D-Ala2,Nle27)GH-RH(1 28)Agm(JG-73) and (D-Ala2)GH-RH(1-29)NH2 showed a potency 2.6-3.9 times greater than GH-RH(1-29)NH2 at 5 min and 1.6-2.7 times higher at 15 min. After SC administration these analogs were 30-74 times more potent than GH-RH(1-29)NH2. The ratio between the IV and SC GH-releasing activity of the analogs ranged from 2 to 5, while GH-RH(1-29)NH2 was about 50 times more active IV than SC. This indicates that 20-50% of the analogs can be absorbed from SC tissues, but only 2% of GH-RH(1-29)NH2. The in vitro activity of the agmatine analogs on GH release closely paralleled their IV potency and was 2.8-3.9 times greater than that of GH RH(1-29)NH2. No significant difference in potency was found between (D-Ala2)GH RH(1-29)NH2 and JG-75 after IV administration and in vitro, although JG-75 contained only 28 amino acids. We conclude that the reason for the large discrepancies between the previously reported activities of (D-Ala2)GH-RH(1 29)NH2 was simply due to the different ways of administration of this analog, SC vs IV, and not to species specificity. The replacement of Arg29 by Agmatine in (D Ala2,Nle27)GH-RH(1-29)NH2 causes a 3 fold increase in SC potency, but the replacement of D-Ala2 with D-MeAla2 reduces the SC, but not the IV and in vitro activity in half. PMID- 2892106 TI - Selective affinity of the benzodiazepines quazepam and 2-oxo-quazepam for BZ1 binding site and demonstration of 3H-2-oxo-quazepam as a BZ1 selective radioligand. AB - Quazepam and 2-oxo-quazepam are novel benzodiazepines containing a trifluoroethyl substituent on the ring nitrogen at position #1. Detailed competition binding experiments (25 to 30 concs.) at 4 degrees C were undertaken with these compounds versus 3H-flunitrazepam using synaptic membranes from rat cortex or cerebellum. Unlike other benzodiazepines, both quazepam and 2-oxo-quazepam distinguished two populations of 3H-flunitrazepam binding sites in rat cortex which were present in roughly equal proportions and for which the compounds displayed a greater than 20 fold difference in affinity. In cerebellum, no such discrimination of sites was noted for 2-oxo-quazepam, but quazepam did distinguish a small, low affinity (15% of total) population of sites. 3H-2-oxo-quazepam was prepared and used in competition studies to substantiate the conclusion that these compounds discriminate two populations of benzodiazepine sites in rat cortex. This new radioligand was shown to specifically label BZ binding sites with high affinity in a saturable manner. The competition experiments were then conducted using 3H-2 oxo-quazepam at a radioligand concentration sufficiently low (0.5 nM) to ensure that only the higher affinity binding sites which 2-oxo-quazepam discriminates would be occupied. Competition experiments in both cortex and cerebellum under these conditions indicated single site binding for unlabelled quazepam and 2-oxo quazepam in every instance. This suggests that 3H-2-oxo-quazepam should be a useful new tool for selectively labeling and studying the BZ1 population of benzodiazepine binding sites. PMID- 2892107 TI - Preferential affinity of 3H-2-oxo-quazepam for type I benzodiazepine recognition sites in the human brain. AB - The hypnotic drug quazepam and its active metabolite 2-oxo-quazepam (2-oxo-quaz) are two benzodiazepines (BZ) containing a trifluoroethyl moiety on the ring nitrogen at position 1, characterized by their preferential affinity for Type I BZ recognition sites. In the present study we characterized the binding of 3H-2 oxo-quaz in discrete areas of the human brain. Saturation analysis demonstrated specific and saturable binding of 3H-2-oxo-quaz to membrane preparations from human cerebellum. Hill plot analysis of displacement curves of 3H-flunitrazepam (3H-FNT) binding by 2-oxo-quaz yielded Hill coefficients of approximately 1 in the cerebellum and significantly less than 1 in the cerebral cortex, hippocampus, caudate nucleus, thalamus and pons. Self and cross displacement curves for 3H-FNT and 3H-2-oxo-quaz binding in these brain areas indicated that 2-oxo-quaz binds with different affinities to two populations of binding sites. High affinity binding sites were more abundant in the cerebellum (95% of total sites), cerebral cortex, hippocampus and thalamus, whereas low affinity sites were predominant in the caudate nucleus and pons. Competition studies of 3H-2-oxo-quaz (2 nM) and 3H FNT (0.5 nM) using unlabelled ligands indicated that compounds which preferentially bind to Type I sites are more potent at displacing 3H-2-oxo-quaz than 3H-FNT from cerebral cortex membrane preparations. The results suggest that 3H-2-oxo-quaz may be used for selectively studying Type I BZ recognition sites in the human brain. PMID- 2892108 TI - Microbial metabolism of phenelzine and pheniprazine. AB - Phenelzine and pheniprazine were used as substrates for metabolic studies with Cunninghamella echinulata and Mycobacterium smegmatis. Metabolites were identified by means of gas-liquid chromatography and mass spectrometry. 1-Acetyl 2-(2-phenylethyl)-hydrazine and 1-acetyl-2-(1-methyl-2-phenylethyl)hydrazine were the major products of C. echinulata metabolism of phenelzine and pheniprazine, respectively. In addition, M. smegmatis produced a second metabolite from each substrate; these metabolites were unequivocally identified as N acetylphenylethylamine and N-acetylamphetamine from phenelzine and pheniprazine, respectively. PMID- 2892109 TI - Antagonistic effect of somatostatin on corticotropin-releasing factor-induced anorexia in the rat. AB - The effect of somatostatin on corticotropin-releasing factor (CRF)-induced anorexia was examined in rats. Intracerebroventricular (icv) administration of 0.11 nmol and 0.21 nmol ovine CRF significantly suppressed food intake of 24 h starved rats. Icv administration of 0.31 nmol somatostatin 14 and somatostatin 28 partially reversed suppression of food intake induced by icv injection of 0.21 nmol CRF in 24 h-starved rats. These results suggest that somatostatin may counteract the suppressive effect of CRF on food intake within the central nervous system. PMID- 2892110 TI - Effect of 7-(3-[4-(2,3-dimethylphenyl)piperazinyl]propoxy)- 2(1H)-quinolinone (OPC-4392), a newly synthesized agonist for presynaptic dopamine D2 receptor, on tyrosine hydroxylation in rat striatal slices. AB - The effects of a newly synthesized compound, 7-(3-[4-(2,3 dimethylphenyl)piperazinyl]propoxy)-2(1H)-quinolinone (OPC-4392), on tyrosine hydroxylation in situ and in vitro were studied using rat striatal slices and tyrosine hydroxylase (TH) purified from bovine adrenal medulla, respectively. OPC 4392 dose-dependently inhibited L-dihydroxyphenylalanine (DOPA) formation in rat striatal slices with IC50 values of about 10(-6) M. The inhibitory effect of OPC 4392 on in situ DOPA formation was dose-dependently reversed by addition of sulpiride, a dopamine D2 receptor antagonist, whereas no change was observed by addition of nomifensine (5 X 10(-6) M), a blocker of dopamine uptake. From in vitro experiment using purified TH, OPC-4392 affected neither the enzymatic activity nor the Km value for 6-methyl-5,6,7,8-tetrahydropterin (6MPH4). These results suggest that OPC-4392 impairs in situ DOPA formation by stimulating presynaptic dopamine D2 receptor as a dopamine agonist, and not by directly inhibiting the TH activity. PMID- 2892111 TI - [The recovery index of vecuronium is potentiated by the pretreatment with pancuronium]. PMID- 2892112 TI - The morbid anatomy of the human genome: a review of gene mapping in clinical medicine. 4. PMID- 2892114 TI - Regulation of hepatic glucose output by glucose in vivo. AB - The effect of infusing glucose at a rate estimated to equal hepatic glucose production (2 mg/kg BW X min) was investigated in postabsorptive unrestrained miniature pigs. Glucose turnover was estimated by the use of 3-H-glucose before and during glucose infusion where the contribution of the glucose-induced hormonal changes were estimated by infusing glucose plus somatostatin with or without insulin and/or glucagon substitution. Our data give evidence for an inhibitory effect of glucose on endogenous glucose production in the postabsorptive state. This effect seems to be independent of the hormonal changes induced by glucose infusion. PMID- 2892113 TI - Prevention of the Dawn phenomenon (early morning hyperglycemia) in insulin dependent diabetes mellitus by bedtime intranasal administration of a long-acting somatostatin analog. AB - Current evidence indicates that resistance to insulin due to nocturnal secretion of growth hormone plays an important role in the Dawn phenomenon and that day-to day variability in growth hormone secretion makes this condition difficult to manage. We therefore assessed the effect of a long-acting somatostatin analog (L363,586) on overnight plasma glucose and growth hormone levels in six patients with insulin-dependent diabetes mellitus. The analog (600 micrograms) was administered intranasally at bedtime to determine whether the inconvenience of an additional injection could be avoided. Compared to control experiments, in which saline was administered intranasally, overnight increases in plasma glucose concentrations were reduced in all subjects by nearly 70% (48 +/- 19 v 148 +/- 26 mg/dL, P less than .01), plasma growth hormone was maintained at basal levels throughout the night (less than 2 v 8 to 12 ng/mL, P less than .01), and the analog was well tolerated. We conclude that pharmacologic blockade of growth hormone secretion may be a helpful approach to management of the Dawn phenomenon when it cannot be done safely and effectively by adjusting insulin doses. PMID- 2892115 TI - Response of ligated rabbit ileal loop to Clostridium perfringens type C strains and their toxic filtrates. AB - The vegetative cells and toxic filtrates of Clostridium perfringens type C strains were injected into ligated rabbit ileal loops and the responses were observed. Out of 12 strains examined, 2 strains showed positive reaction in this test, when the vegetative cells were injected. One of these 2 strains was an enterotoxigenic and beta-toxigenic and the other was beta- and delta-toxigenic but not enterotoxigenic. Culture filtrates containing beta or delta toxin also showed fluid accumulation in the rabbit ileal loop. Histological findings of loops injected with culture filtrates containing beta toxin showed separated and effaced villi, hemorrhage in the mucosa, engorged vessels, inflammatory cell infiltration, and hyperplasia of the lymphoid tissue. PMID- 2892116 TI - Detection of specific antibodies against fimbriae and membrane proteins from the oral anaerobe Bacteroides gingivalis in patients with periodontal diseases. AB - Sera from a number of patients with periodontal diseases were shown to have specific immunoglobulin G (IgG) antibodies against fimbriae and membrane proteins of Bacteroides gingivalis, a suspected pathogen, by using Western blottin analysis. The sera had a strong tendency to react with fimbriae, or exactly oligomeric structures of fimbriae with a native beta-structure rich-conformation. However, the sera did not react with fimbrilin, a constituent protein of fimbriae, which is denatured by sodium dodecyl sulfate. PMID- 2892117 TI - [Ability of yeast mitochondria to transport magnesium ions]. AB - Endomyces magnusii mitochondria were shown to be incapable of active Mg2+ transport at 0.1--16 mM concentrations. As was found using the inhibition analysis, when magnesium ions are added to the mitochondria once the phosphorylation cycle is over, the respiration is stimulated because adenylate kinase and H+-ATPase (Mg2+-dependent enzymes) are activated. PMID- 2892118 TI - Effects of inhibition and modulation of gamma-glutamyltransferase on glutamine and glutamate metabolism in control and acidotic rat proximal tubules. AB - The possible role of gamma-glutamyltransferase (gamma-GT) in renal ammonia production from glutamine remains controversial, prompting the current investigation. In rat proximal tubules, compounds known to activate the enzyme including the endogenously produced organic anion, hippurate, induced a significant increase in glutamine-ammoniagenesis both in nonacidosis and chronic metabolic acidosis although in absolute terms the increase was not more marked under the latter conditions. AT-125, which irreversibly inactivates gamma-GT, but not phosphate-dependent glutaminase, reduced the production of ammonia from glutamine in both acid-base states. In absolute terms, again, this reduction was similar under both acid-base conditions, implying an unimportant role for gamma GT in vitro in the augmentation in renal ammoniagenesis induced by chronic metabolic acidosis. Maleate-stimulated glutamine-ammoniagenesis recently attributed to its intramitochondrial inhibitory effect in the dog is substantially due to the activation of gamma-GT in rat proximal tubules. PMID- 2892119 TI - [Somatostatin-induced changes in the secretion of insulin, glucagon and gastrin in functional hypoglycemia]. PMID- 2892120 TI - The management of coexisting asthma and cardiac disease. AB - We retrospectively reviewed charts of asthmatics who have coexistent cardiac disease. Twenty-nine patients with a mean age of 64.6 received 621 injections of epinephrine for acute asthma. Clinical improvement in asthma was noted and only three patients experienced a total of five (0.8%) adverse reactions temporally related to the administration of epinephrine. Twelve asthmatic patients were treated with beta adrenergic receptor blockers for a coexistent cardiac disease. In general, these patients tolerated the beta-blocker without a significant deterioration in respiratory function. Epinephrine and beta-blockers may be used safely in some asthmatics with heart disease when the medication is indicated and cautiously administered. PMID- 2892121 TI - [Diagnosis of adrenal medullary diseases in patients with sporadic or hereditary medullary thyroid carcinoma. A report of 37 cases with 8-year follow-up study]. AB - Thirty-seven patients with medullary thyroid carcinoma were investigated to determine the status of adrenal medulla by computed tomography and 131I metaiodobenzylguanidine (131I-MIBG) scintigraphy as well as measurements of urinary catecholamine excretion. Patients were followed up for 8 years in maximum. Fifteen patients belonged to multiple endocrine neoplasia type 2 including patients with incomplete phenotype. Computed tomography demonstrated adrenal tumors or enlargement in all 6 patients with urinary epinephrine (E) more than 30 micrograms/day, 4 of them were confirmed to have pheochromocytoma or adrenal medullary hyperplasia by surgery. In 2 patients with E less than 30 micrograms/day and epinephrine to norepinephrine (E/N) ratio more than 0.3 suggesting adrenal medullary hyperfunction, computed tomography revealed small adrenal tumors. Three of the remaining 7 patients with E less than 30 micrograms/day and E/N ratio less than 0.3 had equivocal enlargement of unilateral gland on computed tomography. 131I-MIBG scintigraphy demonstrated tracer uptake in adrenal glands with tumor more than 1cm in diameter. One of 2 adrenal glands with medullary hyperplasia showed a faint adrenal image on the scintiscan, but the other showed no tracer uptake. Pheochromocytoma became manifest in 4 patients during the follow-up period, 4, 13, 14 and 34 years after thyroid surgery. None of 22 patients with sporadic medullary thyroid carcinoma showed adrenal abnormalities on the examinations mentioned above. PMID- 2892123 TI - [Immunocytochemical study of chromogranin on neuroendocrine cells in colorectal cancer]. PMID- 2892122 TI - [An operated case of multiple endocrine neoplasia type IIb and review of the Japanese literature]. AB - Multiple endocrine neoplasia, type IIb (MEN IIb) is a rare syndrome characterized by the occurrence of medullary thyroid carcinoma (MTC), pheochromocytoma and mucosal neuroma. A 35-year-old male patient with MEM IIb having megacolon, marfanoid habitus and no family history of the disease underwent surgery. Because MTC was present in both lobes, total thyroidectomy and modified neck dissection were performed. Pheochromocytoma was found bilaterally and bilateral adrenalectomy with adrenal autotransplantation in the rectus abdominis muscle was carried out. Postoperative course was satisfactory except for transient hypocalcemia and mild ileus. After the slow corticosteroid weaning process, his adrenocortical function was at the lower level within a normal range. In August 1986 (24 postoperative months), he was maintained by the administration of 10mg of hydrocortisone every three days, and calcitonin and CEA levels in sera were normal. We collected 15 cases reported in Japanese literatures. MTC and mucosal neuroma were found in all cases, whereas pheochromocytoma was present in 9 cases. Bilateral and multicentric occurrences were usual, and total thyroidectomy and bilateral adrenalectomy were, warranted. We believe that autotransplantation following bilateral adrenalectomy is a worthy alternative. PMID- 2892124 TI - Agonists and phorbol esters desensitize beta-adrenergic receptors by different mechanisms. AB - Exposure of 1321N1 human astrocytoma cells to the protein kinase C (PKC) activator phorbol 12-myristate, 13-acetate (PMA) led to a rapid and concentration dependent decrease in isoproterenol (ISO)-stimulated adenylate cyclase (AC) activity in cell lysates. This desensitization of beta-adrenergic receptor (BAR) function was mimicked by mezerein, which also activates PKC, but not by 4-O methyl-PMA, which is a very weak activator of PKC. Pretreatment with PMA led to desensitization of AC activity stimulated by ISO and by prostaglandin E1, in contrast to the beta-receptor-specific desensitization induced by ISO. Stimulation of AC activity by forskolin and by fluoride remained unaltered. The extent of desensitization observed with PMA plus ISO was greater than with either agent alone. Desensitization with PMA did not result in internalization of BAR, as assessed by sucrose density gradient centrifugation assays and by assays of competition by the hydrophilic ligand ISO for radioligand binding to intact cell receptors. PMA pretreatment did not alter the apparent affinity of the agonist ISO for intact cell BAR, nor was the potency of ISO for stimulation of AC activity altered. The protein kinase inhibitor H7 [1-(5-isoquinolinesulfonyl)-2 methylpiperazine] inhibited the desensitization induced by PMA but not that induced by ISO. These results indicate that activation of PKC can lead to desensitization of receptor-stimulated AC activity but that agonist-induced desensitization of BAR-stimulated AC activity occurs by a different mechanism. PMID- 2892125 TI - Interaction of L-glutamate and magnesium with phencyclidine recognition sites in rat brain: evidence for multiple affinity states of the phencyclidine/N-methyl-D aspartate receptor complex. AB - Biochemical and electrophysiological studies have provided evidence that a complex comprising the N-methyl-D-aspartate (NMDA)-type excitatory amino acid (EAA) receptor and the phencyclidine (PCP) recognition site exists in mammalian brain. This complex, which has been compared to that established for the inhibitory amino acid, gamma-aminobutyric acid, and the benzodiazepine anxiolytic, diazepam, is sensitive to the effects of the divalent cation Mg2+, which has suggested the presence of a third, ion channel component. Using a radioreceptor assay for the PCP receptor, L-glutamate (L-Glu) produced a concentration-dependent increase in the binding of [3H]thienyl cyclohexylpiperazine ([3H]TCP) in well washed membranes from rat forebrain. The EAA produced a maximal increase in specific binding of 400%, with an EC50 value of 340 nM. The ability of L-Glu to enhance [3H]TCP binding was 10-fold more potent in the presence of 30 microM Mg2+, which inhibits NMDA-evoked responses in intact tissue preparations and produces a 50% increase in [3H]TCP binding on its own. Analysis of saturation curves indicated that the effect of both L-Glu and Mg2+ could be attributed to an increase in receptor affinity as well as increases in the proportion of a high affinity state of the PCP-binding site. Assessment of the effect of a number of EAAs on basal [3H]TCP binding (well washed membranes in the absence of either L-Glu or Mg2+) showed that the EAA recognition site involved in the effects of L-Glu was the NMDA subtype. Further studies examined a series of compounds thought to interact with either the NMDA or PCP components of the receptor complex under four binding conditions: basal, +Mg2+; +L-Glu; and +Mg2+/L-Glu. These results showed that dissociative anesthetics, such as dexoxadrol and PCP, as well as the novel anticonvulsant MK-801, selectively interact with the high affinity state of the PCP receptor. NMDA antagonists, such as CPP, were also found to inhibit binding to the high affinity state of the PCP receptor, although not as potently as the dissociative anesthetics. Interestingly, the NMDA antagonists did not inhibit any of the binding to the low affinity state of the receptor. The sigma ligands (+/-)-SKF 10,047 and haloperidol recognized two components of [3H]TCP binding only in the presence of L-Glu. The results of the present study are consistent with the finding that agonists of the NMDA receptor induce a high affinity state of the PCP receptor. PMID- 2892126 TI - Evidence for multiple tachykinin receptor subtypes on the rabbit iris sphincter muscle. AB - The actions of mammalian tachykinins (substance P, substance K/neurokinin a, neuromedin K/neurokinin b) and non-mammalian tachykinins (eledoisin, kassinin, physalaemin) were compared on the rabbit pupillary sphincter. All acted as direct spasmogens with potencies in the order: eledoisin greater than physalaemin = neurokinin b = substance P greater than kassinin greater than neurokinin a. However, their actions could be divided into at least two categories on the basis of similar kinetics of contractions, differential sensitivity to the tachykinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11) substance P and specific cross protection against phenoxybenzamine inactivation by structurally related tachykinins. The relationship between these observations and the suggested "P" and "E" subtypes of tachykinin receptors is discussed. PMID- 2892127 TI - Clathrin coated vesicles in Neurospora crassa. AB - Electropherograms of Neurospora crassa homogenates showed a polypeptide with a mobility slightly lower than that of a standard sample of clathrin (from bovine brain). Subcellular fractionation of the homogenate resulted in a 20-fold enrichment of the putative N. crassa clathrin in the microsomal fraction. Further fractionation of the microsomal fraction by glass bead permeation chromatography yielded a fraction enriched about 150-fold relative to the homogenate. Coated vesicles (42.5 +/- 2.5 nm diameter) were found in this preparation by electron microscopy of negatively stained specimens. Ribosomes were virtually absent from this sample. N. crassa clathrin remained associated with the coated vesicles after repeated centrifugation and homogenization steps, even in the presence of 0.4 M-NaCl, but was released by treatment with Tris buffer pH 8.5. However the polypeptide was again sedimentable after dialysis against Mes buffer pH 6.5. Under the electron microscope this sediment resembled the empty coats of higher eukaryotes. The results taken together indicate that a clathrin-like protein occurs in wild type cells of N. crassa. PMID- 2892129 TI - DNA probes detect genomic diversity in Theileria parva stocks. AB - Different stocks of Theileria parva were analysed for restriction fragment length polymorphisms by agarose gel electrophoresis, orthogonal-field-alternation gel electrophoresis (OFAGE) and Southern hybridization with DNA probes. Polymorphisms seen with DNA from purified piroplasms of different T. parva stocks, after digestion with restriction enzymes, were more clearly apparent with OFAGE than with standard agarose gel electrophoresis. Genomic differences between these theilerial parasites were investigated further using three DNA probes, which were selected from a genomic library of T. parva (Muguga) piroplasm DNA cloned in lambda gt11. All three clones hybridized to T. parva DNA in preparations from schizont-infected bovine lymphoblastoid cells and to DNA from intraerythrocytic piroplasms. These probes did not, however, hybridize under high stringency conditions to DNA prepared from uninfected bovine lymphoblasts, T. mutans piroplasms, or bovine lymphoblasts infected with T. annulata or T. taurotragi. The five Kenyan stocks of T. parva that were tested showed characteristic hybridization patterns with these DNA probes. Our results show that DNA probes can be used to distinguish selected stocks of T. parva by hybridization to DNA either from intraerythrocytic piroplasms taken from infected cattle, or from isolates of schizont-infected bovine lymphoblastoid cells that are maintained continuously in vitro. PMID- 2892128 TI - A highly evolutionarily conserved mitochondrial protein is structurally related to the protein encoded by the Escherichia coli groEL gene. AB - We recently reported that a Tetrahymena thermophila 58-kilodalton (kDa) mitochondrial protein (hsp58) was selectively synthesized during heat shock. In this study, we show that hsp58 displayed antigenic similarity with mitochondrially associated proteins from Saccharomyces cerevisiae (64 kDa), Xenopus laevis (60 kDa), Zea mays (62 kDa), and human cells (59 kDa). Furthermore, a 58-kDa protein from Escherichia coli also exhibited antigenic cross-reactivity to an antiserum directed against the T. thermophila mitochondrial protein. The proteins from S. cerevisiae and E. coli antigenically related to hsp58 were studied in detail and found to share several other characteristics with hsp58, including heat inducibility and the property of associating into distinct oligomeric complexes. The T. thermophila, S. cerevisiae, and E. coli macromolecular complexes containing these related proteins had similar sedimentation characteristics and virtually identical morphologies as seen with the electron microscope. The distinctive properties of the E. coli homolog to T. thermophila hsp58 indicate that it is most likely the product of the groEL gene. PMID- 2892130 TI - Ceftazidime combined with a short or long course of amikacin for empirical therapy of gram-negative bacteremia in cancer patients with granulocytopenia. AB - To determine whether combination antibiotic therapy including a short course of an aminoglycoside was as effective and less toxic than a conventional long course of the combination for the empirical therapy of gram-negative bacteremia in patients with cancer and granulocytopenia, we conducted a randomized multicenter trial comparing ceftazidime plus a short course (three days) of amikacin, ceftazidime plus a long course (nine days) of amikacin, and azlocillin plus a long course (nine days) of amikacin. Single-organism gram-negative bacteremia occurred in 129 of 872 evaluable patients. Without a change in antibiotics, the response rates were 81 percent with ceftazidime and long-course amikacin, 48 percent with ceftazidime and short-course amikacin (P = 0.002), and 40 percent with azlocillin and long-course amikacin (P less than 0.001). Among patients with fewer than 100 granulocytes per cubic millimeter throughout therapy, the response rates were 6 percent with ceftazidime and short-course amikacin and 50 percent with ceftazidime and long-course amikacin (P = 0.03). Linear logistic-regression analysis showed that therapy with ceftazidime and long-course amikacin was the most favorable prognostic factor of the response to infection, whereas the presence of leukemia or shock was the least favorable. We conclude that ceftazidime should be given in combination with a conventional full course of an aminoglycoside (amikacin) when used for the empirical treatment of gram-negative bacteremia in cancer patients with granulocytopenia. PMID- 2892131 TI - Prediction of the risk of hereditary retinoblastoma, using DNA polymorphisms within the retinoblastoma gene. AB - Using molecular cloning, we earlier isolated the "retinoblastoma gene"; mutations or deletions at this locus are associated with the hereditary predisposition to some human cancers, especially retinoblastoma and osteosarcoma. To develop diagnostic tests for such a predisposition, we identified restriction-fragment length polymorphisms (RFLPs) within the retinoblastoma gene and tested their usefulness in predicting the risk of cancer in 20 families with members who had hereditary retinoblastoma. We were able to make predictions in 19 of the 20 kindreds. In 18 kindreds, we demonstrated a consistent association of marker RFLPs with the mutation predisposing to retinoblastoma. In the 19th kindred, there may be a lack of cosegregation of the DNA polymorphisms within the gene and the site of the mutation predisposing to retinoblastoma. However, there is uncertainty about the clinical diagnosis of the retinal lesion in a key member of this kindred; if the lesion is not a retinoblastoma, there is no discrepancy between the DNA polymorphisms and the retinoblastoma trait. We conclude that it is feasible and clinically useful to use these DNA polymorphisms to determine the risk of cancer. PMID- 2892133 TI - Pathogenic human retroviruses. PMID- 2892132 TI - Infection with human T-cell leukemia virus type I in patients with leukemia. AB - Among 211 adults with leukemia who received multiple transfusions, 6 were found to be seropositive for human T-cell leukemia virus Type I (HTLV-I). Before the positive serum specimens were obtained, these patients received a mean of 14 units of red cells and 78 units of platelets. Seroconversion could be documented in three patients. None of the 6 patients seropositive for HTLV-I had a T-cell leukemia, other illnesses attributable to HTLV-I infection, or risk factors for HTLV-I infection other than transfusion: none were seropositive for human immunodeficiency virus. Patients with leukemia who receive multiple transfusions appear to be at risk for HTLV-I infection. PMID- 2892134 TI - Neurobiology of behavioral control in drug abuse. PMID- 2892135 TI - Receptor regulation as a function of experience. PMID- 2892136 TI - Basic research strategies for imaging neurotransmitter systems. PMID- 2892137 TI - Behavioral contingencies involved in drug-induced neurotransmitter turnover changes. PMID- 2892138 TI - Translational control in homoeobox mRNAs? PMID- 2892139 TI - Prototype PA (Amos Johnson and Henry Treadwell). PMID- 2892140 TI - On child safety. PMID- 2892141 TI - [Glaphenine-induced intravascular hemolysis with acute kidney insufficiency as a consequence of IgG anti-glaphenine antibodies]. PMID- 2892142 TI - Prescription patterns and costs of antihypertensive drugs in two outpatient clinics: Zurich (Switzerland) and Munster (FRG), 1975-1985. AB - In the present study the prescription patterns and cost of antihypertensive drugs in two outpatient clinics located in two different countries (Zurich, Switzerland, and Munster, FRG), were analyzed from 1975 till 1985 by using representative random samples of hypertensive outpatients. Throughout the observed period the leading positions were held by diuretics and beta-blockers, whereas central sympatholytics and ganglion blockers nearly disappeared. A rapid increase in the use of calcium antagonists occurred within the last 2 analyzed years. Drugs in fixed combination containing reserpin showed a constant decrease during the observed period, whereas beta-blocker-containing combination drugs increased in both clinics. The comparison between the two clinics revealed only minor differences in the prescription pattern of the various known classes of antihypertensive drugs. However, marked differences were observed within given classes between the preferred products. Both in Zurich and Munster the mean annual drug cost per patient doubled from 1975 to 1985. Especially during the last few years these changes took place with a remarkable rapidity, obviously the result of a more intense promotion of new antihypertensive drugs. PMID- 2892143 TI - Cross-over factorial studies with antihypertensive drugs. AB - In patients with uncomplicated mild to moderate hypertension, studies employing a double-blind randomized cross-over factorial design have been used to obtain more precise estimates of the hypotensive and biochemical effects of individual antihypertensive drugs and of their interactions when used in combination. Order and carry-over effects have been controlled. In studies with beta-blockers and diuretics, the hypotensive effects of the individual drugs have been confirmed and in combination their effects are additive. With the angiotensin-converting enzyme inhibitor, enalapril (20 mg daily) the hypotensive effect was additive with that of a diuretic, hydrochlorothiazide (50 mg daily). When enalapril was combined with the beta-blocker atenolol (50 mg daily) there was little additional hypotensive effect, despite similar hypotensive effects of the individual agents separately. The mechanism of this attenuated effect is unclear. The design is suitable for evaluation of other antihypertensive combinations. PMID- 2892144 TI - Smoking habits and antihypertensive treatment. AB - Five hypertension intervention trials (HDFP, MRFIT, Australian National BP Study, IPPPSH, MRC) were analyzed for the effect of smoking on antihypertensive therapy and final outcome in coronary and all-cause mortality. In addition, an observational study of primary screenees for MRFIT was reviewed. Thus, the hypertensive population evaluated in this paper amounts to 135,851 patients. HDFP revealed that smokers had about twice the mortality rates compared to nonsmokers regardless of the treatment group to which they were randomized. The annual incidence of events in the Australian Study among nonsmokers in the placebo group was even lightly lower than in smokers under active therapy. The results of the MRFIT showed that smoking had a particularly deleterious impact on those hypertensives whose cholesterol levels were elevated. In this group, the coronary death rates were 10 times higher than in nonsmokers with lower cholesterol levels. Although the treatment with beta-blockers reduced the coronary event rates in the MRC and in IPPPSH, this beneficial effect was absent in smokers. However, in trials in which diuretic treatment is effective in nonsmokers, it is equally effective in smokers. PMID- 2892145 TI - Diurnal variation in prolactin, adrenocorticotropin and corticosterone release induced by opiate agonists in intact and adrenalectomized rats. AB - Diurnal variations of the effectivity of beta-endorphin (beta-End), dynorphin (DYN), Met-enkephalin (Met-Enk), D-Met2-Pro5-enkephalinamide (D-Met-Pro-Enk) and morphine to induce prolactin (PRL) and adrenocorticotropin (ACTH)/corticosterone (CS) release in intact and adrenalectomized rats have been examined. The response to morphine (10 mg/kg s.c.), Met-Enk (200 micrograms/rat i.c.v.) and D-Met-Pro Enk (0.5 microgram/rat i.c.v.) did not change with different times of the day, while that to beta-End (0.5 microgram/rat i.c.v.), DYN (1 microgram/rat i.c.v.) and U50-488H, a selective kappa agonist (10 mg/kg s.c.), showed a circadian rhythm in stimulating PRL release, with a higher increase in the afternoon (16.00 17.00 h) than in the morning (08.00-09.00 h). In adrenalectomized rats the loss of this circadian rhythm was shown. The CS release evoked by morphine, D-Met-Pro Enk, Met-Enk and DYN was demonstrable only in the morning when the basal CS level was significantly lower than in the afternoon. The afternoon release of ACTH by morphine was higher than in the morning in adrenalectomized rats. beta-End and U50-488H were equally active in the morning and in the afternoon in increasing CS secretion. The present results suggest that the diurnal rhythm in the response of CS and PRL release to opioids is in relation with the glucocorticoid secretion. PMID- 2892146 TI - Subdural empyema occurring 20 years after trauma: case report. AB - The authors report a case of subdural empyema that occurred 20 years after a severe closed head injury and was treated surgically with good results. Traumatic subdural empyema of this late onset is rare. The literature is reviewed, and the mechanism of a delayed presentation is discussed. PMID- 2892148 TI - Sinusitis-induced subdural empyema: a case report and brief literature review. PMID- 2892147 TI - Utilization of nurse clinicians and physician assistants by Active members and Fellows of the American Academy of Neurology. AB - A study of 343 Active members and Fellows of the American Academy of Neurology revealed that among 285 responders who spent over 10 hours per week in direct patient care, 198 were in private practice, 69 worked exclusively for institutions, and 18 worked part time in each setting. Eighty-three (29%) used extenders in their practice. Institutionally based neurologists were significantly more likely to use extenders than those in private practice. PMID- 2892149 TI - [The role of surgery in the comparison of peptic ulcer before and after the advent of H2 receptor blockers in the light of our experience]. PMID- 2892151 TI - [Cryptorchism. Anatomo-pathologic and therapeutic considerations]. AB - The authors review the anatomopathological problems about the cryptorchidism. They report a series of 37 cases of cryptorchidism, and discuss about the treatment of them. PMID- 2892150 TI - [Medical therapy of ulcerative rectocolitis]. PMID- 2892152 TI - [Double-blind study on the effects of famotidine on bronchial tone and on expectoration]. AB - A double blind test using famotidine and a placebo was conducted on 14 patients with hypersecretory, chronic bronchitis. No other drug treatment was given during the test or in the ten days preceding it. VC, FEV1, Sgaw and daily excrete volume were measured before the test and 7, 14 and 21 days after it began. The data collected indicate that H2 receptors have no influence on bronchial calibre or secretions. PMID- 2892153 TI - Cytotoxic properties of glutamate and aspartate in rat peripheral nerves: histological findings. AB - Two excitatory neurotransmitters, L-glutamate and L-aspartate, known for their neurotoxic properties in the central nervous system were injected in rat sciatic nerve. The morphological results are compared with sodium chloride injections in sciatic nerve on the other side. Rats were sacrificed 24 h to 1 month after the administration of compounds. Marked endoneural edema with global axonal loss of myelinated fibers were observed in animals injected either with glutamate or aspartate. A demyelinating process was also associated with axonal damages. Sodium chloride did not induce similar morphological abnormalities. This model of toxic neuropathy may be mediated by the excitotoxic properties of L-aspartate and L-glutamate. PMID- 2892154 TI - Somatostatin blocks a calcium current in acutely isolated adult rat superior cervical ganglion neurons. AB - Somatostatin-like immunoreactivity has been reported to occur in the postganglionic neurons of sympathetic ganglia. We therefore investigated the effect of somatostatin (SOM) on the Ca2+ current in sympathetic neurons. Voltage clamp recordings, using the whole-cell patch-clamp technique, were made from acutely isolated adult rat superior cervical ganglion (SCG) neurons in solutions (external and internal) designed to isolate Ca2+ currents. Application of 0.001 1.0 microM [D-Trp8]SOM resulted in a rapid, reversible and concentration dependent decrease in the amplitude of the Ca2+ current evoked from a holding potential of -80 mV. The concentration-response relationship for SOM could be fitted to a single-site binding model with an apparent dissociation constant of 11 nM; the maximal attainable block of Ca2+ current by SOM was 50%. SOM also produced a pronounced slowing of the Ca2+ current rising phase, especially at more depolarized potentials. At higher concentrations (0.03-1.0 microM), prolonged application of SOM resulted in a progressive decrease in blocking ability. The results are consistent with a neurotransmitter and/or neuromodulator role for SOM in the sympathetic nervous system. PMID- 2892155 TI - L-homocysteic acid but not L-glutamate is an endogenous N-methyl-D-aspartic acid receptor preferring agonist in rat neocortical neurons in vitro. AB - The effects of ionophoretically applied L-homocysteate (L-HCA), L-glutamate (L Glu) and N-methyl-D-aspartate (NMDA) were compared in rat neocortical neurons recorded intracellularly in vitro. The firing pattern and the time course of membrane depolarization induced by L-HCA resembled those of NMDA responses. Action potentials evoked by NMDA and L-HCA were superimposed upon slow depolarizations in a burst-like pattern, while L-Glu elicited single spike discharges. Ionophoretically applied D-2-amino-5-phosphonovalerate (2-APV) at doses sufficient to abolish NMDA responses, markedly reduced the L-HCA induced depolarizations but had no detectable effect on the L-Glu responses. The present findings are consistent with a possible role of L-HCA as an NMDA receptor preferring neurotransmitter in the rat frontal cortex. PMID- 2892156 TI - Complex synaptic responses of entorhinal cortical cells in the rat to subicular stimulation in vitro: demonstration of an NMDA receptor-mediated component. AB - Intracellular recordings from neurones in the medial entorhinal cortex of the rat in vitro showed that the lowest threshold response to stimulation in the subiculum was a long latency, prolonged depolarization, which in extracellular records corresponded to a late, negative DC shift. These responses were reduced or abolished by 2-aminophosphonovalerate suggesting mediation via activation of amino acid receptors of the 'N-methyl-D-aspartate'-type. PMID- 2892157 TI - Immunohistochemical distribution of cholecystokinin, dynorphin A and Met enkephalin neurons in sheep hypothalamus. AB - The distribution of cholecystokinin (CCK)-, Met-enkephalin (M-ENK)- and dynorphin (DYN)-like immunoreactive perikarya were examined in the sheep hypothalamus using the peroxidase-anti-peroxidase technique. CCK- and DYN-containing neurons were found primarily in the suprachiasmatic nucleus (SCH) and supraoptic nucleus (SO). No CCK- or DYN-containing neurons were found in the paraventricular nucleus (PVN). M-ENK-containing neurons were found mainly in the PVN of the hypothalamus. In addition, M-ENK neurons were found in the dorsomedial (DMH), lateral (LH), anterior (AH) and periventricular hypothalamic areas. The distribution of these neuropeptides may provide a basis for understanding differences in responsiveness to centrally administered peptides. PMID- 2892158 TI - Evidence for the co-localization of somatostatin- and methionine-enkephalin-like immunoreactivities in raphe and gigantocellularis nuclei. AB - Somatostatin-like and methionine-enkephalin-like immunoreactivities were co localized in neurons in the raphe nuclei and the nucleus gigantocellularis among immunoreactive cells stained for either one of these putative neurotransmitters. Their colocalization suggests that they form a subset of these two peptide populations and may serve as a major inhibitory system within the medullary reticular nuclei. PMID- 2892159 TI - Further studies on the effect of glucose concentrations and other oxidizable substrates upon ionic gradients and in vitro somatostatin release from rat mediobasal hypothalamus. AB - During in vitro incubation of rat mediobasal hypothalamus (MBH), potassium and sodium gradients were high in the presence of glucose, pyruvate, lactate or the mixture glucose and pyruvate; in the absence of substrate, the ionic gradients were markedly lowered and corresponding somatostatin release from MBH was maximal. The specific effect of glucose on somatostatin release from MBH was tested under normal tissue polarization, i.e. in the presence of pyruvate. Under these more physiological conditions, somatostatin release was submaximal and inversely related to glucose concentrations (within the range 0-7 mM). PMID- 2892160 TI - Protein kinase C mediates the stimulation by somatostatin of dopamine synthesis in the rat striatum and nucleus accumbens. AB - In experiments using a synaptosomal preparation from the striatum and nucleus accumbens, somatostatin caused a dose-dependent increase in dopamine synthesis. This increase was additive with that produced by 8-BrcAMP but not with that produced by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and was blocked by the protein kinase C inhibitor polymyxin B (PMB). These findings suggest that stimulation of dopamine synthesis by somatostatin is mediated by activation of protein kinase C. PMID- 2892161 TI - Distinct GABA and glutamate receptors may share a common channel in Aplysia neurons. AB - Using a microperfusion technique for rapid application of agonists to single identified voltage-clamped neurons of the marine mollusc Aplysia, chloride conductances elicited by gamma-aminobutyric acid (GABA) and L-glutamate were found to differ in rates of activation and desensitization, voltage dependence and dose-response relations. In spite of these marked differences, the two responses showed strong interaction: previous application of GABA could completely block the responses to glutamate while previous application of glutamate decreased the response to GABA. This interaction was not due to transmembrane chloride redistribution, and is probably not cross receptor blockade. Cross-desensitization of GABA and glutamate responses suggest that distinct receptors activate a common ion channel. PMID- 2892162 TI - NLN firms links with consumers and constituents--sets sights on quality and access. PMID- 2892164 TI - Improved visualization of the Bst EII RFLP of the human LDL receptor gene by co digestion. PMID- 2892163 TI - Stimulation-produced descending inhibition from the periaqueductal gray and nucleus raphe magnus in the rat: mediation by spinal monoamines but not opioids. AB - Focal electrical stimulation in the midbrain periaqueductal gray (PAG) or medullary nucleus raphe magnus (NRM) inhibits spinal nociceptive transmission and nociceptive reflexes. The purpose of this study was to evaluate, in lightly pentobarbital-anesthetized rats, the spinal neurotransmitter(s) mediating descending inhibition of the nociceptive tail-flick (TF) reflex produced by focal electrical stimulation in the PAG or NRM. To characterize the neurotransmitter(s) mediating inhibition of the TF reflex, selective pharmacologic antagonists were administered into the lumbar intrathecal space. Stimulation thresholds in the PAG or NRM for inhibition of the TF reflex were established and the effects of intrathecally administered phentolamine, yohimbine, prazosin, methysergide (15 micrograms initially, 30 micrograms cumulative) or naloxone (10 micrograms initially, 20 micrograms cumulative) on TF inhibitory thresholds determined. Phentolamine, yohimbine and methysergide increased the intensity of stimulation in the PAG and the NRM for inhibition of the TF reflex; prazosin and naloxone had no effect. Descending inhibition produced by focal electrical stimulation in the PAG or NRM is mediated in part by spinal serotonergic and/or alpha 2-adrenergic receptors. Naloxone was administered both intrathecally and intravenously; however, a role for opioid receptors in descending inhibition from the midbrain or medulla was not found. PMID- 2892165 TI - A Taq I polymorphism in the human P450IIE1 gene on chromosome 10 (CYP2E). PMID- 2892166 TI - Isolation and mapping of a polymorphic DNA sequence pTBAB5.7 on chromosome 2 (D2S47). PMID- 2892167 TI - Isolation and mapping of a polymorphic DNA sequence pYNH24 on chromosome 2 (D2S44). PMID- 2892168 TI - Isolation and mapping of a polymorphic DNA sequence pYNZ9.1 on chromosome 2 (D2S46). PMID- 2892170 TI - Isolation and mapping of a polymorphic DNA sequence pEKZ105 on chromosome 2 (D2S55). PMID- 2892169 TI - Isolation and mapping of a polymorphic DNA sequence pHHH133 on chromosome 2 (D2S45). PMID- 2892171 TI - Isolation and mapping of a polymorphic DNA sequence pHHH115.2 on chromosome 2 (D2S54). PMID- 2892173 TI - Isolation and mapping of a polymorphic DNA sequence pYNZ86.1 on chromosome 3 (D3S30). PMID- 2892172 TI - Isolation and mapping of a polymorphic DNA sequence pEFD122 on chromosome 2 (D2S48). PMID- 2892174 TI - Isolation and mapping of a polymorphic DNA sequence pYNM3 on chromosome 8 (D8S38). PMID- 2892175 TI - A hypervariable RFLP on chromosome 17p13 is defined by an arbitrary single copy probe p144-D6 [HGM9 No. D17S34]. PMID- 2892176 TI - Isolation and mapping of a polymorphic DNA sequence pHHH220 on chromosome 9p (D9S27). PMID- 2892177 TI - Isolation and mapping of a polymorphic DNA sequence pEFD126.3 on chromosome 9q (D9S7). PMID- 2892178 TI - Isolation and mapping of a polymorphic DNA sequence pYNM17 on chromosome 9q (D9S6). PMID- 2892179 TI - Isolation and mapping of a polymorphic DNA sequence pMHZ10 on chromosome 9q (D9S11). PMID- 2892180 TI - Isolation and mapping of a polymorphic DNA sequence pEKZ19.3 on chromosome 9q (D9S17). PMID- 2892181 TI - Isolation and mapping of a polymorphic DNA sequence pEKZ130 on chromosome 9 (D9S9). PMID- 2892182 TI - Isolation and mapping of a polymorphic DNA sequence pEFD40.3 on chromosome 9 (D9S8). PMID- 2892183 TI - Isolation and mapping of a polymorphic DNA sequence pMCT136 on chromosome 9q (D9S10). PMID- 2892184 TI - Isolation and mapping of a polymorphic DNA sequence pMCT112 on chromosome 9q (D9S15). PMID- 2892185 TI - The 5'-O-phosphonomethyl analog of ATP. Studies of substrate properties in ligase dependent reactions. AB - The 5-O-phosphonomethyl analog of ATP (ATPc) and its interaction with different enzymes, catalysing synthesis of C-O-, C-S-, C-N- and C-C-bond were investigated. It was shown ATPc to have substrate properties and to be involved in all studied ligase-dependent reactions. Kinetic parameters of the interaction of alternative substrate - ATPc with all studied enzymes were established and the comparison of ATPc with other phosphonate analogs of ATP was performed. PMID- 2892187 TI - [Use of beta-adrenolytics in the treatment of thyrotoxicosis]. PMID- 2892186 TI - Off the hook. PMID- 2892188 TI - Escherichia coli heat-stable enterotoxins and their receptors. AB - The family of ST has grown to include closely related toxins produced by a number of organisms. The core sequence of these toxins can bind specifically and reversibly to a receptor found in the microvillus membranes of the intestinal cell brush border. As a result of a specific binding event, the ST can stimulate fluid secretion via receptor-mediated stimulation of guanylate cyclase. The structure of the ST molecule has been partially obtained through a variety of techniques. It is apparent that in the near future, key amino acids and sequence regions of these toxins will be found that will identify the requirements for toxicity. The ST are ideal probes to study the secretory system of intestinal cells since they are not cytotoxic. The receptor for ST has been extensively studied and its purification and characterization will yield important insight into the reversal of toxin-mediated diarrheas, and possibly into the nonpathological secretory process. As yet, the nature of the 54,000-57,000 and 68,000-75,000 dalton binding proteins identified by cross-linking studies are not known. When purified ST-binding peptides and other components of the secretory cascade will become available, they will provide better insight into the actual dynamics of the ST receptor-guanylate cyclase complex secretory pathway. PMID- 2892189 TI - Genetic study of piliation in Escherichia coli: implications for understanding microbe-host interactions at the molecular level. PMID- 2892190 TI - [Disseminated media necrosis of the arteries of the base of the skull]. PMID- 2892191 TI - [HIV-2 virus infection with long incubation period]. PMID- 2892192 TI - [Organization of tuberculosis care for the rural population]. PMID- 2892193 TI - First-trimester prenatal gene diagnosis of beta-thalassemia. PMID- 2892194 TI - Release of soluble pilin antigen coupled with gene conversion in Neisseria gonorrhoeae. AB - Gene conversion appears to be the frequent mechanism in Neisseria gonorrhoeae that leads to an altered expression of pilin, the subunit component of the pili. In this process segments of variable sequence information, the minicassettes, are transferred from silent storage loci into an expression locus. As a putative consequence of the rearrangement in the pilE gene, gonococci can enter a different phase of pilin production. Although the removal of a 7-amino acid leader peptide results in the production of typical P+ pilin used to form pili, the loss of an additional 39 amino acids yields S-pilin, a soluble form of pilin that is efficiently secreted into the extracellular environment. Both pilin types can coexist in an apparently homogeneous culture. Ps cells usually are piliated, although less extensively with regard to the length and the number of the pili when compared with P+ cells. Ps cells form T3/T4-type colonies also typical of nonpiliated cells (P-). The observations further suggest that the classical nonsecretory P- phenotype is not generated as a rule by precise gene conversion but rather by genetic changes that cause the production of an over-length pilin (L-pilin). PMID- 2892196 TI - Loss of heterozygosity on chromosomes 3, 13, and 17 in small-cell carcinoma and on chromosome 3 in adenocarcinoma of the lung. AB - By a molecular genetic approach using polymorphic DNA markers that detect allelic deletion of specific chromosomal regions, we analyzed for possible loss of chromosomal heterozygosity in five different histological types of lung cancers obtained from 47 patients. In small-cell carcinomas, the incidence of allelic deletions at three different chromosomal loci was extremely high; loss of heterozygosity was detected on chromosomes 3p in 7 of 7 patients (100%), 13q in 10 of 11 patients (91%), and 17p in 5 of 5 patients (100%). The deletions at these loci in small-cell carcinomas were observed even in the tumors without any clinical evidence of metastasis. Furthermore, loss of heterozygosity on chromosomes 3p and 13q occurred prior to NMYC amplification and chromosome 11p deletion. Loss of heterozygosity on chromosome 3p was also detected with high frequency in adenocarcinomas [5 of 6 patients (83%)]. Heterozygosity of chromosomes 13q and 17p was lost in 10 of 31 patients (32%) and in 3 of 12 patients (25%), respectively, of lung cancers other than small-cell carcinomas. These results indicate that recessive genetic changes involving sequences on chromosomes 3p, 13q, and 17p may play important roles in the genesis of small cell carcinoma, and those on chromosome 3p may play an important role in the genesis of adenocarcinoma. PMID- 2892195 TI - Genetic recombination within the human T-cell receptor alpha-chain gene complex. AB - Genetic analyses of the human T-cell receptor (TCR) alpha-chain genes indicate that recombination events may occur frequently within this gene complex. Examination of the inheritance of restriction fragment length polymorphisms (RFLP) detected by using probes for constant or variable region gene segments made it possible to assign TCR alpha haplotypes to the 16 parents and 43 offspring of eight families studied. A total of six RFLP, three for the constant region and three for variable region gene segments, were examined in the present studies. Most enzyme and probe combinations tested revealed no polymorphism and those finally selected for the study showed limited polymorphism in that only two or, in one case, three allelic forms of the gene were seen. In spite of limited variability at this level, extensive heterogeneity was observed for the combinations of markers present in haplotypes, suggesting that frequent recombination events have occurred. Most strikingly, multiple combinations of RFLP occurring in close proximity of the TCR alpha constant region gene were observed in this study. A high recombination frequency for the TCR alpha gene complex is further supported by the observation that two children, one in each of two families, inherited recombinant TCR alpha haplotypes. PMID- 2892198 TI - Deletion mapping of a locus on human chromosome 22 involved in the oncogenesis of meningioma. AB - The genotypes were analyzed at 11 polymorphic DNA loci (restriction fragment length alleles) on chromosome 22 in tumor and normal tissue from 35 unrelated patients with meningiomas. Sixteen tumors retained the constitutional genotype along chromosome 22, while 14 tumors (40%) showed loss of one constitutional allele at all informative loci, consistent with monosomy 22 in the tumor DNA. The remaining 5 tumors (14%) showed loss of heterozygosity in the tumor DNA at one or more chromosome 22 loci and retained heterozygosity at other loci, consistent with variable terminal deletions of one chromosome 22 in the tumor DNA. The results suggest that a meningioma locus is located distal to the myoglobin locus, within 22q12.3-qter. Multiple loci on other chromosomes also were studied, and 12 of the 19 tumors with losses of chromosome 22 alleles showed additional losses of heterozygosity at loci on one to three other chromosomes. All tumors that retained the constitutional genotype on chromosome 22 also retained heterozygosity at all informative loci on other chromosomes analyzed, suggesting that the rearrangement of chromosome 22 is a primary event in the tumorigenesis of meningioma. PMID- 2892197 TI - Frequencies of independent and simultaneous selection of Chinese hamster cells for methotrexate and doxorubicin (adriamycin) resistance. AB - We have determined the frequency with which Chinese hamster cells become resistant to either methotrexate or doxorubicin (former generic name, adriamycin) alone or to the two drugs simultaneously. We find that the frequency of acquisition of simultaneous resistance is 10-100 times higher than that predicted from the frequency of each resistance selected independently. In approximately 50% of cloned resistant variants, resistance is the result of amplification of the dihydrofolate reductase gene (methotrexate) and/or of the multiple-drug resistance P-glycoprotein gene (doxorubicin). Prior exposure of cells to hypoxia markedly enhances these resistance frequencies. Our results indicate that the simultaneous emergence of resistance to these two cancer chemotherapeutic agents are not independent events, and we interpret them to constitute two consequences of the same basic process occurring at a high frequency. PMID- 2892199 TI - Biochemical correlates of short-term sensitization in Aplysia: temporal analysis of adenylate cyclase stimulation in a perfused-membrane preparation. AB - During short-term sensitization, a simple form of nonassociative learning in Aplysia, the presentation of a single brief noxious stimulus results in enhancement of the defensive withdrawal reflex lasting minutes to tens of minutes. This behavioral plasticity involves presynaptic facilitation of synaptic transmission from the mechanosensory neurons that mediate the reflex to their central target cells. This facilitation is due to cAMP-dependent protein phosphorylation. To determine whether the time course of presynaptic facilitation might be due to a persistent increase in activity of adenylate cyclase (EC 4.6.1.1) itself, persistence of the transmitter, or yet other processes, we developed a perfused-membrane method to analyze the time course of activation of adenylate cyclase by transient stimuli. After stimulation by a pulse of stimulatory transmitter, activation of adenylate cyclase decayed within 60 sec. This finding indicates that the enzyme does not remain persistently active in the absence of transmitter and suggests that short-term retention is likely to be due to other mechanisms. Possible additional mechanisms include continued activation of the cyclase by transmitter, cellular factors extrinsic to the cyclase that prolong the time course of its activation, and persistence of processes downstream from the cyclase. PMID- 2892201 TI - The intracellular pupil mechanism and photoreceptor signal: noise ratios in the fly Lucilia cuprina. AB - The function of the intracellular pupil mechanism is examined by comparing the responses of photoreceptors in normal flies with those from white-eyed flies that lack the pupil. In white-eyed flies the response to an intensity increment of fixed contrast decreases at high background intensities. There is a smaller decrease in noise amplitude so that the signal:noise ratio falls. The intensity dependence of the photoreceptor signal:noise ratio fits a simple model in which activated photopigment molecules compete for 3 X 10(4) transduction units. The signal:noise ratio decreases at high intensities because the transduction units are saturated. This model is supported by a noise analysis, which provides three estimates of the number of events generating photoreceptor responses. In white eyed flies the event number saturates at high background intensities, suggesting that a maximum of 2 X 10(4) events can be simultaneously active. Wild-type flies do not exhibit saturation effects over the range of intensities studied. The signal:noise ratio rises with intensity to reach a stable asymptote, close to the maximum observed for white-eyed flies. Pupil attenuation is calculated from measurements of signal:noise ratio in white-eyed and wild-type flies. The pupil is progressively activated over a two log unit intensity range and when fully closed attenuates the effective intensity by 99%. The threshold of this pupil effect coincides with the threshold of pupil activation measured optically. We conclude that the intracellular pupil attenuates the light flux to prevent receptor saturation and to extend the range of intensities at which fly photoreceptors operate close to their maximum signal:noise ratio. This upper limit is determined by the number of transduction units generating a cell's response. PMID- 2892200 TI - Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase: search for the enzyme's repressor derived from mevalonate. AB - Three inhibitors of squalene 2,3-oxide-lanosterol cyclase (AMO 1618, 4,4,10 beta trimethyl-trans-decal-3 beta-ol (TMD) and 2,3-iminosqualene (ISq] were used to study effects on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and on sterol and polyprenyl synthesis from [14C]acetate and [14C]mevalonate in cultured rat hepatoma (H4) cells. After a 4 h exposure of cultures to AMO 1618 or TMD, followed by removal of the inhibitors, the utilization of [14C]acetate for synthesis of digitonin-precipitable sterols increased about twofold, an increase parallelled by the rise in HMG-CoA reductase. Mevalonate at 2.3 mM counteracted the effects of these inhibitors on the reductase. When (R)-[2-14C]mevalonate at 2.3 mM was included with the two inhibitors in the culture media, the cells were still able to synthesize cholesterol although in lesser amounts than the controls. In the presence of TMD the H4 cells also accumulated [14C]squalene 2,3 oxide and [14C]squalene 2,3-22,23-dioxide. ISq added to cells kept in full-growth medium (10 micrograms ml-1) caused an almost complete and irreversible inactivation of the squalene oxide-lanosterol cyclase but did not inhibit polyprenyl synthesis, as the amount of [14C]mevalonate converted into squalene, squalene 2,3-oxide, squalene 2,3-22,23-dioxide plus a little cholesterol was equal to the amount converted by control cells into cholesterol plus squalene. After a 24 h exposure of cells kept in full-growth medium to ISq (10 micrograms ml-1), the levels of HMG-CoA reductase rose about twofold. ISq completely abolished the suppressive effect of 2.3 mM (R)-mevalonate on the reductase. Chromatin isolated from cell nuclei contains cholesterol, which is renewed biosynthetically. It is argued that the suppressor of HMG-CoA reductase, derived from mevalonate, is a sterol and not a non-steroidal product of mevalonate metabolism. PMID- 2892202 TI - Synaptic limitations to contrast coding in the retina of the blowfly Calliphora. AB - We investigate the effects of synaptic transmission on early visual processing by examining the passage of signals from photoreceptors to second order neurons (LMCS). We concentrate on the roles played by three properties of synaptic transmission: (1) the shape of the characteristic curve, relating pre- and postsynaptic signal amplitudes, (2) the dynamics of synaptic transmission and (3) the noise introduced during transmission. The characteristic curve is sigmoidal and follows a simple model of synaptic transmission (Appendix) in which transmitter release rises exponentially with presynaptic potential. According to this model a presynaptic depolarization of 1.50-1.86 mV produces an e-fold increase in postsynaptic conductance. The characteristic curve generates a sigmoidal relation between postsynaptic (LMC) response amplitude and stimulus contrast. The shape and slope of the characteristic curve is unaffected by the state of light adaptation. Retinal antagonism adjusts the characteristic curve to keep it centred on the mean level of receptor response generated by the background. Thus the photoreceptor synapses operate in the mid-region of the curve, where the slope or gain is highest and equals approximately 6. The dynamics of transmission of a signal from photoreceptor to second-order neuron approximates to the sum of two processes with exponential time courses. A momentary receptor depolarization generates a postsynaptic hyperpolarization of time constant 0.5-1.0 ms, followed by a slower and weaker depolarization. Light adaptation increases the relative amplitude of the depolarizing process and reduces its time constant from 80 ms to 1.5 ms. The hyperpolarizing process is too rapid to bandlimit receptor signals. The noise introduced during the passage of the signal from receptor to second-order neuron is measured by comparing signal:noise ratios and noise power spectra in the two cell types. Under daylight conditions from 50 to 70% of the total noise power is generated by events associated with the transmission of photoreceptor signals and the generation of LMC responses. According to the exponential model of transmitter release, the effects of synaptic noise are minimized when synaptic gain is maximized. Moreover, both retinal antagonism and the sigmoidal shape of the characteristic curve promote synaptic gain. We conclude that retinal antagonism and nonlinear synaptic amplification act in concert to protect receptor signals from contamination by synaptic noise. This action may explain the widespread occurrence of these processes in early visual processing. PMID- 2892203 TI - On the evolution of sex determination. AB - Female mice reject skin grafts from intrastrain males because of the H-Y transplantation antigen. Those females produce antibodies that recognize a male specific cell-surface antigen in serological tests. The serological antigen has also been called 'H-Y', but there is evidence that the two antigens are distinct. We therefore refer to the transplantation antigen as H-Yt, or transplantation H Y, and to the serological antigen as serological H-Y, or simply H-Y, without prejudice whether these are the same or related or separate antigens. In this study, sex-specific expression of serological H-Y antigen was found in 25 new vertebrate species representing each of seven major vertebrate classes. There was a strong correlation between expression of H-Y and occurrence of the heterogametic-type gonad, although unusual patterns of H-Y expression were noted in cases of temperature-influenced sex determination and in systems representing possible transition from one mode of heterogamety to the other. Male and female heterogamety are found side-by-side in certain freshwater toothed carps; and distinct sex chromosomes have been recognized in certain amphibians, even though they are not apparent in certain reptiles and primitive birds. In seven ophidian species, in which the female is the heterogametic sex, H-Y was detected in the female; and in three species of Ranidae in which the male is heterogametic, it was detected in the male. In three species of cartilaginous fish and in one of the cyclostomes, in which heterogamety has not been ascertained, H-Y was detected in the male, suggesting that those primitive fishes are male-heterogametic. Evidently, then, heterogamety and sex-chromosome heteromorphism are polyphyletic, although certain sex-determining genes may be held in common among the diverse taxonomic groups. PMID- 2892204 TI - The morphology and distribution of 'Kolmer-Agduhr cells', a class of cerebrospinal-fluid-contacting neurons revealed in the frog embryo spinal cord by GABA immunocytochemistry. AB - An immunocytochemical method that localizes GABA in glutaraldehyde-fixed tissue has been applied to the study of the Xenopus embryo spinal cord. This procedure stained an anatomical class of neuron, which had somata forming two more or less continuous rows, one on either side of the central canal, in the ventral part of the spinal cord. The total number of stained neurons in the stage 37-38 embryo spinal cord was about 300. The medial surface on the soma protruded into the central canal and had a brush border which electron microscope studies showed to consist of many microvilli or stereocilia and one or two cilia. The external end of the neuron soma had an ipsilateral ascending axon. The axon of many of these neurons had a growth cone which was also clearly stained. We propose calling these neurons 'Kolmer-Agduhr cells' after W. Kolmer and E. Agduhr who described them in the spinal cords of many vertebrate classes. Their early embryonic origin, GABA-like immunoreactivity, axonal projections and distribution as a whole population have not previously been known. PMID- 2892205 TI - The development of a population of spinal cord neurons and their axonal projections revealed by GABA immunocytochemistry in frog embryos. AB - The development of a population of cerebrospinal-fluid-contacting neurons in the spinal cord of the Xenopus embryo ('Kolmer-Agduhr' cells) has been followed by using an immunocytochemical procedure that identifies GABA in fixed nervous tissue. Stained Kolmer-Agduhr cells containing GABA first appeared at stage 25 and their numbers increased steadily with the developmental age of the embryo. The Kolmer-Agduhr neurons had ascending ipsilateral axons that often terminated in growth cones. These axons and growth cones could be stained by the GABA antiserum from the earliest stages of outgrowth from the Kolmer-Agduhr cell body. We measured the angle of the earliest axons' outgrowth relative to the rostrocaudal axis of the spinal cord. The initial outgrowth of axons was always rostral over a narrow range of angles. This observation is inconsistent with the hypothesis of random initial outgrowth followed by later selection of the correct orientation, which would predict that axons would initially grow out over a wide range of angles. Instead, it suggests that, even from the earliest moments, axon outgrowth from the Kolmer-Agduhr cells is directed rostrally in a specific stereotyped manner. PMID- 2892206 TI - Tension responses to increased hydrostatic pressure in glycerinated rabbit psoas muscle fibres. AB - A method developed to study the effect of increased hydrostatic pressure on the isometric tension of a single muscle fibre is described and experiments done at room temperature (18-22 degrees C) on glycerinated rabbit psoas muscle fibres are presented. Increase of pressure (range 1-10 MPa) caused little change in tension transducer response when a muscle fibre was relaxed. However, there was a reversible depression of isometric tension with an increase of pressure when a fibre was maximally calcium-activated or in rigor; the depression was around 15% for active tension and 30% for rigor tension, for an increase of pressure of 10 MPa (ca. 100 atm). PMID- 2892207 TI - The resting release of acetylcholine by a retinal neuron. AB - The cholinergic amacrine cells of the rabbit retina secrete acetylcholine by two mechanisms. One is activated by stimulation of the retina by light or depolarization of the amacrine cells by K+ ions. It requires the presence of extracellular Ca2+. The second is independent of extracellular Ca2+ and is unaffected by large depolarizations of the cells. It bears some similarity to the acetylcholine 'leakage' described at the neuromuscular junction. Although the Ca2+-independent mechanism accounts for about two thirds of the total acetylcholine release in the dark, the amount of acetylcholine released in this way is small compared with the release of acetylcholine triggered by stimulation of the retina with light. Its biological significance is unclear. PMID- 2892208 TI - Single-channel and whole-cell currents evoked by acetylcholine in dissociated sympathetic neurons of the rat. AB - Single acetylcholine-activated channels have been recorded from neurons dissociated from the sympathetic chain of 17-21 day old rats. The mean single channel conductance is 35 pS in normal medium containing 1 mM calcium, and 51 pS in the absence of calcium. The measured current amplitudes are about five times more variable than at the frog endplate, at least in part because the current, while the channel is open, is much noisier than when it is shut. Single activations of the receptor by acetylcholine (ACh) produce a burst of openings; the distribution of the burst length has two components, the longer of which is of primary importance in synaptic transmission. Whole-cell currents, in response to ACh (up to 30 microM), show strong inward rectification with no outward current being detectable. This phenomenon is similar whether the intracellular ion is sodium or cesium, whether or not divalent cations are present, and whether or not atropine is present. Nevertheless, outward single-channel currents (of normal conductance) are detectable in isolated outside-out patches. PMID- 2892209 TI - Influence of gastrointestinal peptides on bile acid transport by isolated rat hepatocytes. AB - While numerous effects of gut peptides on gastric, pancreatic, and intestinal secretion have been described, there has been little investigation of the influence of these peptides on hepatic function. In the present studies, effects of vasoactive intestinal peptide (VIP), somatostatin, thyrotropin-releasing hormone (TRH), and bombesin on taurocholate transport by isolated rat hepatocytes have been examined. Somatostatin, TRH, and bombesin in incubation media produced no change from control incubations with regard to either uptake of taurocholate by hepatocytes or efflux of bile acid from preloaded cells. However, incubation of hepatocytes with VIP produced a significant decrease in taurocholate uptake (1.34 +/- 0.13 versus 1.73 +/- 0.16 nmole.min-1.10(6) cells-1, P less than 0.001). Studies with verapamil, a calcium-channel blocking agent, and theophylline, an inhibitor of cAMP catabolism, failed to provide evidence for transmembrane Ca2+ flux or alteration in intracellular levels of cAMP, respectively, as mechanisms for the observed inhibition of hepatocyte taurocholate uptake by VIP. These data, coupled with both clinical and other basic observations, suggest that VIP may play a significant role in the regulation of hepatic bile secretion. PMID- 2892210 TI - Infantile polyarteritis and fatal cases of Kawasaki syndrome: two diseases or one? PMID- 2892211 TI - Dietary linolenic acid in man--an overview. AB - Small amounts of linolenic acid are ubiquitous in human food but only a few foodstuffs contain sizable amounts, namely some plant oils, butter and fish; in marine fish, linolenic acid is accomplished by eicosapaentaenoic acid, highly exceeding linolenic acid in quantity. Of the linolenic acid ingested, some is incorporated into phospholipids and cholesteryl esters, very little is elongated and eventually converted to prostaglandins; probably most linolenic acid is used as fuel. Polyunsaturated fatty acids of the (n-3)-series should no longer be considered to be similar with respect to their metabolic fate and their effects. In particular, results from experiments with "eskimo diets" may not be applied to considerations of linolenic acid. There may be a small dietary requirement for linolenic acid, possibly only for growing children; yet it is prudent to recommend diets which are not devoid of linolenic acid, especially in formula diets or parenteral nutrition. Some experiments suggest that high doses of linolenic acid exert untoward effects by inhibiting prostaglandin synthesis of the 1- and 2-series. The ratio between linoleic and linolenic acid in relevant experiments was such that only excessive use of linseed oil could produce them under conventional dietary conditions. Still it must be considered prudent to keep the linolenic acid content of foods well below that of linoleic acid. PMID- 2892212 TI - Adverse reactions to benzodiazepine hypnotics: spontaneous reporting system. AB - The rates of reported adverse drug reactions involving the central nervous system were compared among patients taking any of three benzodiazepine hypnotics: flurazepam, temazepam, and triazolam. These rates, based upon data collected through the spontaneous reporting system of the Food and Drug Administration, were controlled for the number and size of new prescriptions for each drug. In general, triazolam had much higher overall rates than did the other two drugs. Hyperexcitability and withdrawal effects were greatest for triazolam and least for flurazepam. Amnesia was reported almost exclusively with triazolam. Rates for other cognitive as well as affective and other behavioral effects were also much greater for triazolam and about equal for the other two drugs. Finally, daytime sedation was reported slightly more for flurazepam than triazolam and least for temazepam which was also reported most frequently as lacking hypnotic effect. PMID- 2892213 TI - Genetic aspects of resistance to anticancer drugs. PMID- 2892214 TI - ATP synthesis by oxidative phosphorylation. PMID- 2892215 TI - Accumulation of biological amines into chromaffin granules: a model for hormone and neurotransmitter transport. PMID- 2892216 TI - Apolipoprotein genetic variation and human disease. AB - Atherosclerosis is the major public health problem in much of the world today. The information summarized in this review, based on the recognized apolipoprotein structural variants appreciated at both the protein and gene levels, indicates that apolipoprotein genetic variation plays a major role in determining human genetic susceptibility to this disease. With the use of cloned apolipoprotein genes, it should, in the near future, be possible to determine how their expression is regulated; this should provide insight into other classes of mutations of a regulatory nature that might have clinical significance. In addition, the many association and linkage studies currently being undertaken will provide the rationale for cloning defective alleles and determining specific causative mutations. Both structural and regulatory mutations can then be described either with restriction enzymes and Southern blotting or by direct oligonucleotide hybridization techniques in the general population. This will allow the identification of presymptomatic atherosclerosis-susceptible individuals who would be targets for primary preventative therapy. PMID- 2892217 TI - Glutamate dehydrogenase and glutamine synthetase activity of the bacteria of the sheep's rumen after different nitrogen intake. AB - In experiments on 18 sheep with a differentiated nitrogen intake (3.7, 6.2 and 21 g N/day), it was found that different enzyme activities--glutamate dehydrogenase (GDH) (NADH- and NADPH-dependent) and glutamine synthetase (GS)--of bacteria adhering to the rumen wall and to food particles and the rumen fluid bacteria altered in correlation to the nitrogen intake. With a nitrogen intake of 3.7-6.2 g/day there was a significant increase, and of 6.2-21 g/day a decrease, in NADH- and NADPH-dependent GDH activity in the three given bacterial fractions, with the exception of NADPH-dependent GDH activity of the rumen fluid bacteria of sheep given 3.7-6.2 g N/day, in which the difference was nonsignificant. GS activity was significantly higher only in adherent rumen wall bacteria in the presence of a nitrogen intake of 3.7-6.2-21 g/day. The results show that the effect of the nitrogen intake on the given enzyme activities is strongest in the case of bacteria adhering to the rumen wall. The high GS activity and low GDH activities in these bacteria during lower nitrogen intakes (3.7 g/day) as well as lower rumen ammonia concentration (2.39 +/- 0.98 mmol.l-1) indicate that bacteria adhering to the rumen wall utilize ammonia at an increased rate by means of CS catalyzed reactions. Reduced GDH activity in the presence of a high nitrogen intake (21 g/day) and the relatively high rumen ammonia concentration (36.63 +/- 5.28 mmol.l-1) indicate that ammonia inhibits this enzyme in the rumen bacteria in question. PMID- 2892218 TI - The lateral supramalleolar flap. AB - An anatomic study (40 fresh dissected specimens) and clinical experience (14 patients) have shown the reliability of a skin flap designed on the lower third of the lateral aspect of the leg. It is supplied by a cutaneous branch from the perforating branch of the peroneal artery. This perforating branch continues distally deep to the fascia along the anterior ankle and into the foot. This can be used as a reversed pedicle, giving the flap an arc of rotation that allows coverage of the dorsal, lateral, and plantar aspects of the foot, the posterior heel, and the lower medial portion of the leg. PMID- 2892219 TI - [Biological markers of depression]. PMID- 2892220 TI - [Biochemical presynaptic and receptor adaptations during long-term antidepressive treatment]. PMID- 2892221 TI - Antihistaminics enhance morphine-, but not amphetamine- and scopolamine-induced hyperactivity in mice. AB - Three histamine H1-receptor antagonists, chlorpheniramine, diphenhydramine and tripelennamine, were tested alone or in combination with morphine, amphetamine and scopolamine on locomotor activity in mice. All three antihistaminics, at some dosage levels, enhanced morphine-induced hyperactivity, but did not change or even reduce locomotor stimulation induced by amphetamine and scopolamine. The results suggest that H1-blocking agents may specifically interact, though not necessarily directly, with opiate mechanisms in producing behavioural effects. PMID- 2892222 TI - Stability of serum neuroleptic and prolactin concentrations during short- and long-term treatment of schizophrenic patients. AB - The potential importance of neuroleptic activity measures in the management of schizophrenia warrants attention to the methods for assessing neuroleptic bioactivity and stability of neuroleptic bioactivity over time. We have carried out measurements of serum neuroleptic and prolactin concentrations in 18 schizophrenic patients treated with haloperidol or thioridazine for up to 1 year. Serum neuroleptic levels were measured by a radioreceptor assay using porcine striatum. The lower limit of sensitivity of the assay was 0.6 ng haloperidol/ml, the intra- and interassay coefficients of variation 3 and 9%, respectively. A linear correlation was observed between haloperidol dose (5-30 mg/d) and serum neuroleptic activity (r = 0.706, P less than 0.001) and a curvilinear relationship between thioridazine dose (50-600 mg/d) and serum neuroleptic activity in schizophrenic outpatients. There was a positive correlation between serum neuroleptic and prolactin concentrations for the patients taking haloperidol (r = 0.620, P less than 0.001) or thioridazine (r = 0.542, P less than 0.001). In patients taking a constant dose of haloperidol or thioridazine for up to 1 year serum neuroleptic activity remained stable, suggesting the absence of metabolic tolerance; the observation of a decrease of 38 +/- 16% (mean +/- SD) in serum prolactin concentrations in patients treated with haloperidol but no prolactin decrease with thioridazine suggests that under certain neuroleptic treatment conditions a functional tolerance develops in the tuberoinfundibular dopamine system. PMID- 2892223 TI - Dysphoric states in the course of manic-depressive illness. AB - The purpose of the present study is to investigate the relationship between dysphoric states (episodes in which irritable mood is prominent and relatively persistent) and manic-depressive illness. A further purpose is to clarify the probable causal influence of chemotherapy and the social consequences concerning dysphoria. The observations carried out on 14 patients are illustrated by 2 case reports. A strong tie seems to exist between dysphoric state and manic-depressive illness, especially with respect to typical biorhythmic disturbances. Although the origin of such states is generally unknown, there are indications that neuroleptics and lithium may play a major role. Social consequences are on the whole minor, if the disturbances in mood and drive occur acutely and markedly. On the other hand, mild to moderate mood changes (especially when unaccompanied by drive changes) may lead to severe social impairment. The reason for this may be that the latter-mentioned states are misinterpreted by the entourage as personality traits rather than as expressions of an illness. PMID- 2892224 TI - Biochemical aspects of dysphoria: case study for hypothesis generation. AB - Comparing the pattern of serotonin, 5-hydroxyindole acetic acid, 3,4 dihydroxyphenyl acetic acid and homovanillic acid in five brain areas of one dysphoric patient to those of 3 depressed patients it seems that dysphoria biochemically is a state between depression and mania. Dynamically, dysphoria may possibly be seen as a behavioral correlate of a switch process between high and low turnover of neurotransmitters (rather high frequency in comparison to bipolar disorder with very low frequency). However, the biochemical data are obviously in agreement with psychiatric findings, i.e. that dysphoria in any case is an extremely labile state. PMID- 2892225 TI - Pharmacology of antidepressants. AB - Choice of an antidepressant medication is, in part, based on the side effects produced by a drug and the desire to avoid certain reactions in a particular patient. The clinician needs a reliable method of predicting which medications are most likely to produce specific untoward effects. Understanding the synaptic pharmacology of the most commonly used agents could serve as a tool for predicting possible side effects and drug-drug interactions. Antidepressant drugs alter neurotransmitter effects at nerve synapses, probably by blocking norepinephrine and serotonin reuptake, and blockade of neurotransmitter receptor sites - primarily the histamine H1 receptor, the muscarinic receptor, and the alpha-1-adrenoceptor. Possible clinical side effects related to some of these interactions include tachycardia, tremor, and (possibly) male sexual dysfunction (associated with norepinephrine reuptake blockade); sedation (associated with histamine H1 blockade); orthostatic hypotension, dizziness, and reflex tachycardia (associated with alpha-1-adrenoceptor blockade), and blurred vision, dry mouth, and memory dysfunction (associated with muscarinic receptor blockade). Pharmacologic data that demonstrate the potencies and selectivities of the antidepressant drugs for reuptake blockade and receptor site antagonism might allow the clinician to make an informed, rational choice of antidepressant therapy. This paper presents data on drug potencies and selectivities, and attempts to relate these data to anticipated side effects and drug-drug interactions. PMID- 2892226 TI - Neuroleptics following NMS. PMID- 2892227 TI - Prolegomenon to the clinical prerequisite: psychopharmacology and the classification of mental disorders. PMID- 2892228 TI - [Ultrasensitive enzyme immunoassay]. PMID- 2892229 TI - Is cytoprotection by misoprostol against ethanol-induced gastric mucosal injury in man mediated by somatostatin? PMID- 2892230 TI - [Mechanisms for the maintenance of Gamboa virus in the mosquito Aedeomyia squamipennis]. PMID- 2892231 TI - [Outline of principal diseases transmitted by insects in Panama]. PMID- 2892232 TI - Analysis of restriction fragment length polymorphisms in rheumatic diseases. AB - Considerable evidence indicates that genes residing within the major histocompatibility complex (MHC) influence susceptibility to certain rheumatic diseases, such as ankylosing spondylitis (AS) and rheumatoid arthritis (RA). However, it has not yet been possible to precisely identify the gene(s) responsible for conferring enhanced susceptibility to these diseases. The availability of recombinant DNA technology should accelerate progress in obtaining this goal. A particularly promising method in this regard is restriction fragment length polymorphism (RFLP) analysis using appropriate class I and class II MHC gene probes. In preliminary studies, RFLPs have been identified for AS and RA which associate with susceptibility to the disease. Further studies using this approach should permit localization and precise identification of the disease susceptibility gene(s) for these diseases. PMID- 2892233 TI - Molecular cytology of microtubules. PMID- 2892234 TI - [Use of priming with fazadinium]. PMID- 2892236 TI - Exocrine pancreatic response to secretin and bethanechol in rabbits under hypothermia. AB - The effect of the administration of secretin and bethanechol on exocrine pancreatic secretion was studied in rabbits subjected to temperature changes; these involved a drop from 38 degrees C +/- 1 to 28 degrees C +/- 1 (hypothermia) and a subsequent return to 38 degrees C +/- 1 (normothermia). It was observed that hypothermia does not depress the action of secretin on the secretion of fluid, HCO3- and Cl-. Neither was the action of bethanechol on the enzyme secretion affected by changes in body temperature. PMID- 2892235 TI - [Chronic effect of prazosin and yohimbine on the renal epinephrine content of DOCA-sodium and SHR-hypertensive rats]. AB - The chronic effect of two alpha-adrenergic receptor blockers, prazosin and yohimbine, on the renal noradrenaline (NA) content was investigated in two models of hypertensive rats, the DOCA-salt and the spontaneously hypertensive rats (SHR). In DOCA-salt rats an inversal relation exists between the level of blood pressure and renal NA content in all groups studied, except those treated with yohimbine and prazosin plus yohimbine. In SHR rats a decreased renal NA content has been detected with respect to their normotensive Wistar-Kyoto (WKY) rat controls. The administration of prazosin and/or yohimbine did not alter the renal NA content of the SHR rats, while on the contrary these agents produced an elevation of these levels in kidneys from normotensive WKY rats. These results suggest that the alpha-selective blocker agents used, demonstrate a different effect on the renal NA content in the two models of hypertension studied. PMID- 2892237 TI - Effect of somatostatin on leucine-aminopeptidase activity in the small intestine. PMID- 2892238 TI - [Peripheral neuropathy caused by almitrine. 2 cases]. PMID- 2892239 TI - [Psychotic disorders linked to the inhibition of benzodiazepine catabolism]. AB - Five clinical cases of interaction between benzodiazepines on one hand and erythromycin, troleandomycin, josamycin and cimetidine on the other hand have been analyzed. These interactions resulted in severe disorders of behaviour, amnesia (including amnesia-automatism syndrome in one case), disturbances of consciousness and withdrawal syndrome. These disorders were consecutive to inhibition of the hepatic cytochrome P-450 system. Practical means of avoiding this risk consists in limiting such drug combinations, reducing benzodiazepine dosage and, if a combined treatment is necessary, using by preference either benzodiazepines degraded by conjugation instead of oxidation, or macrolides, or anti-H2 compounds with reduced inhibitory effect on microsomes. PMID- 2892240 TI - [Molsidomine in the treatment of coronary insufficiency]. AB - Molsidomine, a predominantly venous vasodilator, has been coronary disease. The basic mechanism of its anti-anginal effect is a reduction in myocardial oxygen consumption due to a fall in left ventricular end-diastolic pressure resulting from the vasodilator action of the drug. To this may be added direct dilatation of the main coronary vessels on the surface of the heart, which may account for part in its therapeutic effects in unstable and vasospastic angina. The effectiveness of molsidomine has been evaluated by controlled drug versus placebo or drug versus reference anti-anginal drug studies in 3 types of angina pectoris: exertion, unstable and vasospastic. The usefulness of the drug has also been established in acute and chronic left ventricular failure of ischaemic origin. Because of its high bioavailability when administered orally, molsidomine shows little inter-individual variations in its pharmacodynamic effects. Unlike nitrates, it can be administered for long period without gradual loss of activity with time. Finally, on several experimental models molsidomine has been shown to exert an antiplatelet effect, but the therapeutic implications of this finding have yet to be evaluated. PMID- 2892241 TI - [Current developments in the therapy of anxiety states]. PMID- 2892242 TI - [Metabolic consequences of a 6-hour interruption of a continuous subcutaneous insulin infusion pump in insulin-dependent diabetic patients]. PMID- 2892243 TI - [Hemorrhagic fevers with renal syndrome caused by Hantaan virus in France]. PMID- 2892244 TI - [Astemizole and terfenadine: comparison of their therapeutic effect in pollen rhinitis]. PMID- 2892245 TI - [Peptic ulcer: how to treat it long term]. PMID- 2892246 TI - [How do we treat the anxious patient?]. PMID- 2892247 TI - Olsalazine in patients intolerant of sulphasalazine. AB - Fifty patients with ulcerative colitis, intolerant of sulphasalazine, were treated with 500 mg olsalazine twice daily for a 3-month trial period. Thirty eight of the patients (76%) tolerated the drug well, and all continued to take it beyond the 3-month period. Twelve (24%) were withdrawn because of side effects, the commonest being diarrhoea. There were no haematologic or biochemical abnormalities. Thus, olsalazine is a useful drug for patients who are intolerant of sulphasalazine. PMID- 2892248 TI - Effect of a somatostatin analogue, SMS 201-995, on 133Xe clearance from colonic mucosa in unanesthetized man. AB - The effect of intravenous bolus injection of the somatostatin analogue SMS 201 995 on mucosal and submucosal blood flow was studied with the local 133Xe clearance technique in eight subjects. Mucosal and submucosal blood flow decreased by 33% after injection of SMS 201-995. These observations suggest that SMS 201-995, like somatostatin, inhibits splanchnic blood flow. PMID- 2892249 TI - Pharmacology and toxicology of nizatidine. AB - In well-established animal models, nizatidine is a potent, specific, and competitive orally active H2-receptor antagonist. In rat and dog models, species in which the absorption, plasma half-life and routes of metabolism are similar to that of humans, nizatidine was three- to four-fold more active than cimetidine and was of similar potency to ranitidine. On repeated daily dosing in dogs for two weeks, no tolerance was developed to the pharmacological action. Following oral dosing to dogs, nizatidine reduced gastric acid secretion for up to 8 h suggesting that this compound could be used in humans with a once or twice daily dosage regime. Apart from its H2-antagonist activity on the gastric mucosa, nizatidine produced few effects on the cardiovascular, respiratory, or central nervous system of animals. Nizatidine was rapidly and well-absorbed orally in mice, rats, and dogs, was widely distributed in tissues and the majority of the dose was excreted in the urine within 24 h. A similar absorption and excretion profile has been seen in humans. The plasma half-life in each of the animal species was between 1 and 2 h and no accumulation of nizatidine or its metabolites was seen in rats or dogs after daily oral administration for long periods. Similarities in the pharmacokinetic profile of nizatidine in the laboratory animals and humans supported the selection of the mouse, rat, and dog for acute and chronic toxicity studies. Nizatidine was well-tolerated in animals after both intravenous and oral administration and following single or repeated administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892250 TI - Nizatidine in peptic ulcer disease. Proceeedings of the First International Symposium on Nizatidine. Vienna, 11 and 12 October 1986. PMID- 2892251 TI - Lack of effect of nizatidine on drug metabolism. AB - H2-receptor antagonists are among the most widely-used drugs in the world and, since many patients receive a variety of other drugs concomitantly, it is important to investigate the interaction potential of new H2-receptor antagonists such as nizatidine. It is well documented that cimetidine can inhibit the hepatic elimination of many drugs by binding to the cytochrome P-450 system. Therefore we investigated in vitro and in vivo the effects of nizatidine on drug metabolism. With rat liver microsomes the effects of nizatidine and four other H2-blockers (cimetidine, oxmetidine, ranitidine, famotidine) on the activity of three marker enzymes (aryl-hydrocarbon-hydroxylase, 7-ethoxycoumarin-O-deethylase, 7-ethoxy resorufin-O-deethylase) were tested. While cimetidine and oxmetidine exhibited marked and dose-dependent inhibition of all three metabolic reactions, nizatidine showed some weak inhibition only at very high concentrations. Similarly, binding to cytochrome P-450 of human liver microsomes could be seen only with cimetidine and oxmetidine, whereas nizatidine did not affect the binding spectra. In nine healthy mal volunteers the pharmacokinetics of diazepam (10 mg po) was studied under the influence of nizatidine (300 mg day nocte). Nizatidine had no significant effect on the hepatic elimination of diazepam, as characterized by its elimination half-life (mean +/- SD) of 35.3 +/- 24.2 h (control) and 37.3 +/- 18.3 h (+ nizatidine) or its total plasma clearance of 28.2 +/-12.0 ml/min (control) and 26.7 +/- 10.4 ml/min (+ nizatidine). The formation of the major metabolite-desmethyldiazepam-was also unaffected by nizatidine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892252 TI - An evaluation of the anti-androgen effects associated with H2 antagonist therapy. AB - The effect of two different H2-receptor antagonists, nizatidine and cimetidine, on sperm counts and hypothalamic-pituitary-gonadal function as determined by responses to provocative gonadotropin releasing factor, GnRH, thyrotropin releasing factor, TRH, and clomiphene were compared to those of men receiving placebo medication. All subjects studied gave informed written consent and were greater than 18 but less than 55 years of age. Sperm concentrations in collected semen specimens, and GnRH and TRH responses before and after 6 weeks of drug exposure were assessed as were the gonadotropin responses to clomiphene while on the drug for an additional 3 weeks. All had normal sperm concentrations and hormone levels before drug exposure and normal responses to both GnRH and TRH. Following drug exposure, the LH response to GnRH and the growth hormone, prolactin, TSH and T4 responses to TRH were similar to those obtained prior to drug use. Sperm concentrations were unchanged in both placebo and nizatidine exposed men, but were significantly reduced (p less than 0.05) in the cimetidine exposed men. Based on these data, nizatidine does not appear to influence hormone function or fertility. PMID- 2892253 TI - Safety of nizatidine in clinical trials conducted in the USA and Europe. AB - The safety of nizatidine as treatment for active duodenal or gastric ulcer disease or as maintenance therapy following ulcer healing was assessed in 3800 nizatidine-treated individuals in clinical trials conducted in the USA and Europe. Safety parameters included physical examinations, electrocardiograms, eye examinations, serum chemistries and testosterone, hematology, and urinalyses. Adverse events were recorded without judgment of causality. Early discontinuations and adverse events, including complications of active duodenal ulcer disease, occurred more frequently in placebo-treated patients than in those given nizatidine. No differences were observed between the nizatidine and ranitidine treatment groups in regard to adverse event incidence or severity. Minimal changes in uric acid values were observed during ranitidine and nizatidine therapy. Abnormal liver function tests occurred infrequently and to an equal extent in nizatidine and placebo treatment groups. No clinically relevant differences in laboratory test results were observed between treatment groups in studies conducted in Europe. PMID- 2892254 TI - The effect of an oral evening dose of nizatidine on nocturnal and peptone stimulated gastric acid and gastrin secretion. AB - An evening oral dose of nizatidine, a new H2-receptor antagonist, was tested for its ability to suppress nocturnal gastric acid secretion and to inhibit food stimulated acid secretion the following day. Using a double-blind, randomized, cross-over design, nizatidine 30, 100, and 300 mg and placebo were compared in 8 male subjects with basal acid secretion greater than or equal to 3 mmol/h. Continuous nasogastric suction was started 2 h after oral dosing, and acid secretion was measured hourly overnight. Phenol red was used to determine the completeness of gastric aspiration. The following day, food stimulated acid secretion in response to 8% peptone meals was measured by intragastric titration to determine the carry-over effect of nizatidine. Serum gastrin levels were measured by RIA. Nizatidine inhibited overnight acid secretion in a dose-related manner with 30, 100, and 300 mg producing 57, 73, and 90% suppression. The effect was long-lasting, with nizatidine 300 mg decreasing acid secretion by 52% 10 h after administration. Peptone stimulated acid secretion on the following day was not inhibited by nizatidine. Gastrin levels did not differ significantly among the treatment groups. Nizatidine's effects on nocturnal acid secretion therefore resemble other H2-receptor antagonists. PMID- 2892255 TI - Treatment of duodenal ulceration in the United States. AB - Nizatidine, a new H2-receptor antagonist for the treatment of duodenal ulcer disease, was compared with placebo in a dose-response, double-blind, parallel, multicenter clinical trial. Patients were randomly allocated to receive either nizatidine (25 mg b.i.d., 150 mg b.i.d., or 300 mg at bedtime) or placebo. At the end of 4 weeks, patients whose ulcer had not healed were randomly reallocated to receive either the nizatidine 150 mg b.i.d. dosage regime or placebo for an additional 4 weeks. Nizatidine doses of 300 mg at bedtime and 150 mg b.i.d. demonstrated similar healing frequencies. Both of these doses were statistically significantly superior in ulcer healing to the nizatidine 25 mg b.i.d. dose and to placebo at the end of 4 weeks. Patients randomly reallocated to receive nizatidine had significantly greater healing rates than patients randomly reallocated to receive placebo. In summary, nizatidine given as a single evening dose of 300 mg or as 150 mg b.i.d. proved to be equally safe and effective in the healing of active duodenal ulcers. PMID- 2892256 TI - The 24-hour acid suppression profile of nizatidine. AB - To determine the antisecretory potency of bedtime doses of the new thiazole H2 receptor antagonist nizatidine in the suppression of nocturnal acid secretion, this randomized, cross-over, single-blind study was performed in 10 healthy male subjects. The actions of a single bedtime (2100 h) dose of the H2-receptor antagonist nizatidine (150 mg and 300 mg), ranitidine (300 mg), cimetidine (800 mg), and famotidine (40 mg), as well as placebo on nocturnal gastric acid and volume secretion (2400 to 0600 h) and on overall 24 h H+-ion concentration were studied. Compared with placebo, night-time (2300 to 0700 h) H+ ion concentration was reduced by 70, 79, 95, 75, and 89% (p less than 0.05 to p less than 0.01). Nocturnal acid secretion, too, was significantly lower for the H2-blockers than for placebo (p less than 0.01). A significant reduction in total night-time gastric volume secretion was observed (p less than 0.01). Nizatidine 300 mg nocte, ranitidine, cimetidine and famotidine had no significant carry-over effects on daytime acidity (0800 to 1800 h). No significant pharmacodynamic differences between nizatidine 300 mg nocte, ranitidine 300 mg nocte, cimetidine 800 mg nocte and famotidine 40 mg nocte were observed. Thus, it may be concluded that these four H2-blockers will be equally effective in accelerating peptic ulcer healing and pain relief. PMID- 2892257 TI - 300 mg nizatidine at night versus 300 mg ranitidine at night in patients with duodenal ulcer. A multicentre trial in Europe. AB - Patients (859) from six countries were randomized into an endoscopically controlled double-blind trial. The objective of this study was to compare the efficacy and safety of nizatidine 300 mg nocte with ranitidine 300 mg nocte in the therapy of duodenal ulceration. Patients fulfilling the entry criteria and completing the protocol numbered 777 (388 nizatidine, 389 ranitidine). Endoscopy was performed on entry and at 4-week intervals (up to 8 weeks) until the ulcer healed, except in Germany where endoscopy was also performed after 14 days. Both groups appeared well matched for population demographics, duodenal ulcer history, previous therapy and pre-study symptomatology. Overall healing rates in the nizatidine group compared favourably with the ranitidine group at 4 weeks (nizatidine 81%, ranitidine 80%) and 8 weeks (nizatidine 92%, ranitidine 93%). Data from Germany alone showed similar ulcer healing rates after 2 weeks therapy (nizatidine 60%, ranitidine 64%). Although there were no differences between or within the treatment groups, overall ulcer healing was significantly impaired (p less than 0.05 or less) in patients with a large ulcer (greater than 15 mm), a family history of peptic ulcer disease, verified disease or greater than 5 years duration, or heavy smokers (greater than 20 cigarettes/day). Age did not influence healing. Overall healing rates were significantly influenced by country of patient origin, being higher in Germany, and lower in Belgium (p less than 0.001). After 2 weeks therapy, about 60% of the nizatidine and ranitidine treated patients were pain free, while 4 weeks therapy was associated with relief of all symptoms in 72% of patients and relief of night pain in more than 90%. Antacid consumption reduced at a similar rapid rate during the study. Events were reported equally in both treatment groups, events compatible with peptic ulcer disease predominating. Events associated with study termination appeared related to documented disease or protocol violations. Monitoring of laboratory data suggested no significant haematological or biochemical abnormalities in the nizatidine group. Nizatidine 300 mg nocte appears to be as effective as ranitidine 300 mg nocte in both ulcer healing and symptomatic response. PMID- 2892258 TI - Nizatidine versus ranitidine in gastric ulcer disease. A European multicentre trial. AB - Two hundred and seventy five patients from six countries were randomized into an endoscopically controlled, eight-week, double-blind, study. The objective of this investigation was to compare the efficacy and safety of nizatidine, administered as either a single (300 mg nocte) or twice daily (150 mg B.D.) dose, with ranitidine 150 mg twice daily, in the therapy of benign gastric ulceration. Two hundred and fifty-two patients fulfilled entry criteria and completed the protocol (80 nizatidine 150 mg B.D.; 89 nizatidine 300 mg nocte; 83 ranitidine 150 mg B.D.). Endoscopy was performed on entry and at four-week intervals until the ulcer healed. The diagnosis of benign ulceration was always supported by endoscopic histology and/or cytology. On entry into the study, both groups appeared well matched (i.e. for population demographics, duodenal ulcer history, previous therapy and pre-study symptomatology), except for epigastric day pain which was significantly less in the ranitidine group (p = 0.020). Overall gastric ulcer healing rates were similar in the three groups at four weeks (nizatidine B.D. 66.2%: nizatidine nocte 65.2%: ranitidine B.D. 63%) and at eight weeks (nizatidine B.D. 90%: nizatidine nocte 86.5%: ranitidine B.D. 86.7%). Healing was not consistently influenced by country of origin or smoking. After four weeks of therapy, 66% (nocte dose) to 68% (B.D. dose) of nizatidine treated patients were symptom free, while 93% (nocte dose) to 95% (B.D. dose) were free of night pain. Events were similar in the three treatment groups, and the majority were gastro intestinal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892259 TI - Nizatidine as maintenance therapy of duodenal ulcer disease in remission. AB - A new H2-receptor antagonist, nizatidine (150 mg h.s.), was compared with placebo as maintenance therapy in a randomized, parallel, double-blind, one-year study of 513 patients with recently healed duodenal ulcer. Endoscopies were performed at 0, 3, 6, and 12 months and at unscheduled times if symptoms of active peptic ulcer disease were present. Cumulative ulcer recurrence rates for nizatidine and placebo were 13 versus 40% at 3 months, 24 versus 57% at 6 months, and 34 versus 64% at 12 months. The differences were significant (p less than 0.001) at each treatment period. Smokers in both treatment groups had significantly greater recurrence rates than non-smokers. Symptoms of peptic ulcer disease were significantly less in nizatidine-treated patients in the first 3 months of treatment. Adverse events, including those related to peptic ulcer disease, occurred more frequently in placebo-treated patients. Nizatidine proved to be safe and effective in preventing recurrences of duodenal ulcer. PMID- 2892260 TI - Nizatidine versus ranitidine in the prevention of duodenal ulcer relapse. Six month interim results of a European multicentre study. AB - Nizatidine, a new H2-receptor antagonist, was compared with ranitidine in a double-blind, randomized, multicentre trial for the prevention of duodenal ulcer relapse. This is the interim analysis of 197 patients admitted to the study by 1 September 1985, having finished a 6-month treatment period by 1 March 1986. At night, 96 and 101 patients received 150 mg nizatidine and 150 mg ranitidine, respectively. Both groups were well matched for demographic data, duration and severity of ulcer disease. Calculating cumulative relapse rates by the life-table method of Cutler and Ederer, 18% on nizatidine and 13% on ranitidine had experienced a symptomatic or asymptomatic recurrence. The difference is not statistically significant. The symptomatic response was identical in both groups, 3/4 of the patients in both groups being free of any symptom over all 6 months. During maintenance treatment, 24% of the patients on nizatidine and 32% of those on ranitidine reported new symptoms, listed as 'adverse events'. However, none of these events was likely to be drug related. There was no difference between the two groups concerning the percentage change of laboratory variables from baseline to endpoint. PMID- 2892262 TI - Role of histamine H2 receptor antagonists in nonoperative management of gastroduodenal ulcer haemorrhage. AB - Acute massive gastroduodenal ulcer haemorrhage may be caused by peptic ulcers or acute stress ulcerations. The former is a clinical problem that is met with fairly frequently, associated with a mortality of 10-20%. Bleeding stress ulcerations are less common but have a still more serious prognosis. The histamine H2-receptor antagonist cimetidine has in one large study been demonstrated to reduce mortality in ulcer haemorrhage, and in other studies beneficial effects have been found in elderly patients; above all in elderly gastric ulcer patients. Other authors again find no beneficial effects. The inconsistent results can be due to the fact that other factors, such as high age, profuse bleeding, and concomitant disabling diseases, are more important for the outcome than inhibiting acid secretion with H2-receptor antagonists. In stress ulcers, H2-receptor antagonists have been shown to be effective as part in the prophylactic treatment. Antacids might be more effective, but high doses are often required. PMID- 2892261 TI - A pharmacokinetic profile of nizatidine in man. AB - In this report, the pharmacokinetic, pharmacodynamic, and hormonal effects of nizatidine are reviewed in healthy volunteers and in patients with renal or hepatic impairment. The absolute oral bioavailability of nizatidine exceeded 90%; the half-life (t1/2), plasma clearance (Clp), and volume of distribution (Vd) of iv nizatidine were 1.3 h, 461/h, and 1.21/kg, respectively. Within 16 h of dosing volunteers with nizatidine, more than 90% of the administered dose was recovered in urine as parent drug and metabolites; unchanged nizatidine accounted for 65 and 75% of the recovered substances, after oral and intravenous administration, respectively. Renal impairment decreased the elimination of nizatidine and dosage reductions are recommended for patients with creatinine clearance (Clcr) less than 50 ml/min/m2. Nizatidine suppressed gastric acid secretion produced by sham meals, protein meals, or pentagastrin; its antisecretory activity was dose and concentration dependent. Nizatidine was three times more potent than cimetidine. Nizatidine, after oral or iv administration, did not alter hormone concentrations in plasma. PMID- 2892263 TI - Vasopressin and glypressin in upper gastrointestinal bleeding. AB - Vasopressin has been in clinical use for more than two decades in the treatment of upper gastrointestinal haemorrhage, especially bleeding oesophageal varices. However the haemostatic effect in controlled clinical trials is far from impressive, and no double-blind placebo controlled trial has shown even a trend in favour of vasopressin. These studies, the effects, side-effects, and clinical use of vasopressin and its long-acting analogue triglycylvasopressin, glypressin, are reviewed. PMID- 2892264 TI - Secretin and somatostatin in the treatment of upper gastrointestinal haemorrhage. AB - Secretin inhibits gastric secretion of acid and gastrin in dog and a physiological role of secretin as an enterogastrone has been suggested in this species. In man there are diverging results concerning the effect of secretin on gastric secretion. Secretin has been used in patients with upper gastrointestinal bleeding and positive results have been reported, but the patients included in these studies cannot be considered as massive bleeders. Until now no double-blind study comparing secretin with placebo has been reported. Somatostatin decreases splanchnic blood flow and gastric secretion in man. Somatostatin seems to be effective in achieving initial haemostasis in patients with bleeding oesophageal varices. The peptide has also been shown to stop severe and persistent peptic ulcer haemorrhage and to stop bleeding in patients treated with steroidal and non steroidal anti-inflammatory drugs. In one double-blind trial in patients with upper gastrointestinal bleeding, somatostatin had no effect on either the number of emergency operations or the number of rebleedings. In another double blind study, when somatostatin was compared with placebo in patients with massive upper gastrointestinal bleeding, the peptide reduced the number of emergency operations. In conclusion, most studies show positive effects of somatostatin on variceal and peptic ulcer haemorrhage. PMID- 2892265 TI - Drug treatment of haematemesis and melaena. AB - Despite generally held beliefs to the contrary, worthwhile improvements in outcome in patients with haematemesis and melaena may be achievable with H2 antagonist or antifibrinolytic treatment. PMID- 2892266 TI - Meeting on the mind. PMID- 2892267 TI - Expression and function of the segmentation gene fushi tarazu during Drosophila neurogenesis. AB - Segmentation genes control cell identities during early pattern formation in Drosophila. One of these genes, fushi tarazu (ftz), is now shown also to control cell fate during neurogenesis. Early in development, ftz is expressed in a striped pattern at the blastoderm stage. Later, it is transiently expressed in a specific subset of neuronal precursor cells, neurons (such as aCC, pCC, RP1, and RP2), and glia in the developing central nervous system (CNS). The function of ftz in the CNS was determined by creating ftz mutant embryos that express ftz in the blastoderm stripes but not in the CNS. In the absence of ftz CNS expression, some neurons appear normal (for example, the aCC, pCC, and RP1), whereas the RP2 neuron extends its growth cone along an abnormal pathway, mimicking its sibling (RP1), suggesting a transformation in neuronal identity. PMID- 2892269 TI - Long-term facilitation in Aplysia involves increase in transmitter release. AB - In a variety of vertebrates and invertebrates, long-lasting enhancement of synaptic transmission contributes to the storage of memory lasting one or more days. However, it has not been demonstrated directly whether this increase in synaptic transmission is caused by an enhancement of transmitter release or an increase in the sensitivity of the postsynaptic receptors. These possibilities can be distinguished by a quantal analysis in which the size of the miniature excitatory postsynaptic potential released spontaneously from the presynaptic terminal is used as a reference. By means of microcultures, in which single sensory and motor neurons of Aplysia were plated together, miniature excitatory postsynaptic potentials attributable to the spontaneous release of single transmitter quanta from individual presynaptic neurons were recorded and used to analyze long-term facilitation induced by repeated applications of 5 hydroxytryptamine. The results indicate that the facilitation is caused by an increase in the number of transmitter quanta released by the presynaptic neuron. PMID- 2892268 TI - Somatostatin augments the M-current in hippocampal neurons. AB - Immunocytochemical and electrophysiological evidence suggests that somatostatin may be a transmitter in the hippocampus. To characterize the ionic mechanisms underlying somatostatin effects, voltage-clamp and current-clamp studies on single CA1 pyramidal neurons in the hippocampal slice preparation were performed. Both somatostatin-28 and somatostatin-14 elicited a steady outward current and selectively augmented the noninactivating, voltage-dependent outward potassium current known as the M-current. Since the muscarinic cholinergic agonists carbachol and muscarine antagonized this current, these results suggest a reciprocal regulation of the M-current by somatostatin and acetylcholine. PMID- 2892270 TI - Bureaucratic aspects of international health agencies. AB - In this paper the large international health agencies are viewed as bureaucracies, i.e. in Max Weber's sense as rational administrative organizations. The kinds of activities in which they engage, and the effectiveness of their programs, are interpreted as a function of their structural and dynamic characteristics, and of the professional assumptions held by administrators, planners and technical specialists. International health agency activities are placed in the context of the 'donor-recipient' model that characterizes post-World War II international developmental assistance programs. Some of the strengths and weaknesses of these organizations are noted, and linked to the organizations' structural, dynamic and professional characteristics. PMID- 2892271 TI - [Benzodiazepines]. PMID- 2892272 TI - P-fimbriated Escherichia coli urinary tract infection: a clinical correlation. AB - We designed a retrospective study to determine the incidence of P-fimbriated Escherichia coli in patients with asymptomatic bacteriuria, acute urethral syndrome, bacterial cystitis, acute pyelonephritis, possible acute pyelonephritis, and acute and chronic prostatitis. In addition, we compared the incidence in uncompromised vs compromised hosts, inpatients vs outpatients, and children vs adults. P-fimbriated E coli were isolated in more than 80% of uncompromised patients with either acute pyelonephritis or acute prostatitis. In clinically compromised patients having these disorders, the incidence dropped to approximately 30% (P less than .025). Neither age nor inpatient/outpatient status was a significant factor. We stress the importance of P-fimbriation as a virulence factor in acute pyelonephritis and acute prostatitis caused by E coli, though these diseases may be caused by less virulent organisms in compromised patients. Thus, patients with acute pyelonephritis or acute prostatitis caused by E coli negative for P-fimbriae probably should be considered compromised; the compromising factor should be determined as a guide to subsequent treatment. PMID- 2892273 TI - Fab fragments in the treatment of digoxin overdose: pediatric considerations. AB - Serious digoxin toxicity due to accidental or deliberate overdose is uncommon, but more than half of the cases reported in 1985 involved children. Toxicity can occur acutely, as with accidental overdose, or with long-term maintenance dosing. In children it is almost always acute. Conventional treatment includes gastric lavage or ipecac-induced emesis, and activated charcoal or nonabsorbable resins and cathartics to reduce absorption. Although children appear to tolerate massive ingestions without specific therapy, serum digoxin levels must be reduced quickly and safely when conventional measures have failed. Fab fragments of digoxin specific antibodies have been successfully used to treat refractory digoxin toxicity. Indications for use should be limited to life-threatening digoxin toxicity when conventional therapy has failed. PMID- 2892274 TI - [The role of anaerobic non-clostridial microflora in the development of complications after appendectomy]. PMID- 2892275 TI - Characterisation of poxviruses from sporadic human infections. AB - An orthopoxvirus was isolated from the vesicular rash of a man in Natal who died in coma and who had not been vaccinated. Analysis of the viral DNA showed that it was a vaccinia virus, more closely related to the virus of South African smallpox vaccine than to other vaccinia viruses. DNA analysis also showed that an orthopoxvirus isolated from a sporadic case of severe pustular rash in Nigeria was a vaccinia virus closely related to the smallpox vaccine virus used there. Minor biological differences between the viruses isolated and the corresponding vaccine strains suggested that some natural transmission of the virus had occurred, but the results of DNA analysis implied that they originated from the use of smallpox vaccine. No similar cases have been detected since smallpox vaccination was discontinued. PMID- 2892277 TI - Benefit of somatostatin in dumping syndrome. PMID- 2892276 TI - Early diagnosis of and surgical strategy for adrenal medullary disease in MEN II gene carriers. AB - Sixteen multiple endocrine neoplasia type II (MEN II) gene carriers--12 who had undergone thyroidectomy because of medullary carcinoma of the thyroid and 4 whose thyroid glands had been removed because of C cell hyperplasia--were examined for the presence of pheochromocytomas. No patient had sought medical advice for pheochromocytoma symptoms. Fourteen patients had MEN IIa syndromes, one patient had a MEN IIb and another patient had a mixed syndrome of von Recklinghausen's neurofibromatosis and MEN II. Eight patients had undergone unilateral adrenalectomy for pheochromocytoma 11 +/- 4 years before. The patients underwent clinical examination, determination of the urinary excretion of catecholamines and metabolites, and 131I-metaiodobenzylguanidine (131I-MIBG) and CAT scans. 131I MIBG scanning was performed with images 1, 4, and 7 days after the radionuclide injection. In seven of eight patients who had undergone unilateral adrenalectomies, the 131I-MIBG scans showed accumulation of the radionuclide in the remaining adrenal gland. Bilateral adrenal accumulation of the radionuclide was demonstrated in seven of eight MEN IIa gene carriers who had not undergone adrenalectomy. Five patients, two of whom had undergone adrenalectomy, were found to have unilateral pheochromocytomas less than 2 cm in diameter. Only one of these five patients had an elevated excretion of urinary catecholamines. Between day 4 and day 7 after 131I-MIBG injection, adrenal glands with pheochromocytomas increased their relative accumulation of the radionuclide significantly more (p less than 0.02) than did adrenal glands without any demonstrable pheochromocytomas. All the pheochromocytomas were viewed by means of CAT scans. Only one MEN IIa patient had bilateral pheochromocytomas, but our findings indicate that there is a tendency to bilateral adrenal medullary hyperfunction in most MEN II gene carriers. As 131I-MIBG and CAT scans can facilitate the early diagnosis of pheochromocytomas, unilateral adrenalectomy can safely be performed in most MEN IIa patients. Bilateral pheochromocytomas develop in a majority of patients with MEN IIb syndromes. Bilateral adrenalectomy should therefore be performed in these patients. PMID- 2892278 TI - [Various forms of asthma agents and treatment]. PMID- 2892279 TI - [Importance of alcoholism markers in the diagnosis of alcoholic heart lesions]. AB - A study was made of opportunities for the use of some signs of alcoholic intoxication in the verification of alcoholic etiology of heart lesion. Clinical signs like hyperemia of the face with telangiectasia, venous plethora of the eyeballs, tremor of the lips, tongue, limbs, Dupuytren's contracture, enlarged liver size combined with a positive macrocytosis test and, to a lesser degree, with a higher activity of gamma-glutamyl transpeptidase, and the detection of fatty hepatosis in liver puncture biopsy were shown to suggest alcoholic intoxication, and excluding other cases of heart lesion they can be of great help in the verification of diagnosis of alcoholic heart lesion. PMID- 2892280 TI - Increased plasma motilin concentrations in small cell carcinoma of the lung. AB - Plasma samples from 21 patients with small cell carcinoma of the lung were screened for pancreatic polypeptide, somatostatin, motilin, and vasoactive intestinal polypeptide. One patient had severe impairment of both renal and liver function. In the 20 remaining subjects vasoactive intestinal polypeptide concentrations were normal, and only two patients had increased concentrations of somatostatin. Increases in pancreatic polypeptide were detected more commonly (7/20), but these may have been non-specific age related increases. The major finding was high concentrations of motilin (greater than 496 pg/ml) in 17 of 20 patients. Plasma motilin was subsequently assayed in 16 more patients with lung cancer, including 10 patients with non-small cell carcinoma of the lung. At concentrations over 900 pg/ml plasma motilin appears to be a tumour marker for small cell carcinoma of the lung with acceptable sensitivity (59%) and specificity (78%). The origin of increased plasma motilin in small cell carcinoma of the lung was investigated. Bombesin (gastrin releasing peptide), a peptide known to stimulate the release of motilin in man, was, as in previous studies, detected in tumour but not in plasma, except in one patient out of 21. Immunohistochemical studies failed to detect motilin antigen in biopsy samples. Motilin tumour content was found to be low in tumour tissue from three patients with small cell carcinoma of the lung who had appreciable hypermotilinaemia and from three patients with non-small cell carcinoma of the lung who had either normal or slightly raised plasma motilin concentrations. The stimulus to motilin secretion in patients with small cell carcinoma of the lung remains unclear. PMID- 2892281 TI - RFLP of the HLA-DQ alpha region: a diallelic DX alpha polymorphism, not linked to DR and DQ specificities. AB - HLA-DQ alpha DNA polymorphism was studied by Southern blot analysis in a panel of 117 individuals, consisting of 56 randomly selected and 61 HLA-DR homozygous individuals. Hybridizing fragments representing DQ alpha genes correlate with DR specificities owing to linkage disequilibrium between DQ and DR. Two fragments representing DX alpha genes were identified with the restriction enzymes PvuII and TaqI and a DQ alpha cDNA probe. The two fragments of PvuII-DQ alpha hybridization (a 7200 and a 7000 basepair fragment) and the two of TaqI-DQ alpha (2200 and 1900 basepairs) have an identical distribution in the panel, and reveal gene frequencies of 49.1% and 50.9%; they behave as alleles of the putative DX alpha locus. The panel study shows that the DX alpha fragments are not linked with the DR or DQ specificities but segregate along with HLA as shown in family studies. PMID- 2892282 TI - Genomic HLA-typing by RFLP-analysis using DR beta and DQ beta cDNA probes reveals normal DR-DQ linkages in patients with multiple sclerosis. AB - Eighteen MS patients were HLA-typed by RFLP-analysis using DR beta and DQ beta cDNA probes. A closer association to the DQ than to the DR locus was not found in this small material, not even within DR-specificities. PMID- 2892283 TI - Genomic HLA-typing by RFLP-analysis using DR beta and DQ beta cDNA probes reveals normal DR-DQ linkages in patients with psoriasis vulgaris. AB - Thirty-five patients with psoriasis vulgaris were HLA-typed by RFLP-analysis using DR beta and DQ beta cDNA probes. A closer association to the DQ than to the DR locus was not found in this small material. PMID- 2892284 TI - Transfer of di(2-ethylhexyl) phthalate through rat milk and effects on milk composition and the mammary gland. AB - Five daily oral doses of di(2-ethylhexyl) phthalate (DEHP) (2 g/kg) given to rats on Days 2-6, 6-10, or 14-18 of lactation caused significant decreases in body weight and increases in hepatic peroxisomal enzymes palmitoyl CoA oxidase and carnitine acetyltransferase in the dams and their suckling pups. Plasma cholesterol and triglyceride levels were decreased in the lactating dams. Decreased food consumption, as indicated by pair-fed rats, accounted for the decreased body weight in the pups but not the increases in enzyme activities. To determine whether DEHP and mono(2-ethylhexyl) phthalate (MEHP) were transferred through the milk, milk and plasma were collected from lactating rats 6 hr after the third dose of DEHP. The milk contained 216 +/- 23 micrograms/ml DEHP and 25 +/- 6 micrograms/ml MEHP (mean +/- SE), while the plasma contained less than 0.5 micrograms/ml DEHP and 75 +/- 12 micrograms/ml MEHP. The high milk/plasma ratio for DEHP (greater than 200) indicates efficient extraction of DEHP from the plasma into the milk. DEHP dosing during lactation also caused a decrease in mammary gland weight and a decrease in mammary gland RNA content which reflects synthetic activity. The water content of the milk was reduced, which probably accounted for the increase in lipid in the milk. Milk lactose was decreased in DEHP-treated and pair-fed rats, consistent with the decrease in milk production. The results show that exposure to high doses of DEHP during lactation in rats can result in changes in milk quality and quantity and can lead to DEHP and MEHP exposure in the suckling rat pups. PMID- 2892285 TI - Red blood cells generate nitric oxide from directly acting, nitrogenous vasodilators. AB - Human red blood cells (RBC) incubated under nitrogen with methylene blue and glucose at physiological temperature and pH can be used to test for the biotransformation of nitrogenous vasodilators to nitric oxide (NO). The NO generated was trapped as nitrosylated heme by reduced subunits (hemeII) on various hemoglobin valency species and quantified by electron paramagnetic resonance spectroscopy. It was possible to separate the various valency species of hemoglobin present in the mixture as (alpha 2 + beta 2)2, (alpha 2 + beta 3+)2, (alpha 3 + beta 2+)2, or (alpha 3 + beta 3+)2 by isoelectric focusing (IEF) unless cyanide (from nitroprusside) or azide was present in the mixture. These anions bind tenaciously to oxidized subunits (hemeIII) and prevent the separation of the various species by IEF. The fully oxidized tetramer, (alpha 3 + beta 3+)2, does not bind NO, but the other three species have hemeII units which can be nitrosylated. In the absence of cyanide or azide the valency species could be separated by IEF, and it was possible to quantify the degree of nitrosylation on each individual species. The various agents tested (nitrite, glyceryl trinitrate, hydroxylamine, hydralazine, nitroprusside, and azide) produced different patterns of valency species and degrees of nitrosylation of hemeII. When hemeIII ligands were present or in cases of very low yields, it was still possible to quantify the total concentration of NO-hemeII in the mixture. Thus, the method could still be used to test for NO formation. All of the so-called NO vasodilators tested yielded detectable amounts of NO in the system. PMID- 2892286 TI - Anti-convulsant effects by reduced glutathione and related aminoacids in rats treated with isoniazid. AB - Rats were treated with different doses of isoniazid (INH) causing convulsions. Lethal dose (DL50) and effective convulsant dose (ED50) were calculated. Reduced glutathione (GSH) and related aminoacids were administered to rats receiving INH: the latency and duration of convulsions were recorded; cerebral gamma aminobutyric acid (GABA) concentrations were determined in rats receiving INH and an association of GSH and INH. GSH and its related aminoacids as cysteine and glycine greatly decreased the duration of INH-induced seizures, while glutamic acid did not protect against convulsions caused by INH. Furthermore, INH causes a decrease in cerebral GABA levels to about half and GSH repeated pretreatment did, however, not prevent the INH induced decline of GABA content: hence, the anticonvulsant effect of GSH can not be ascribed to the restoration of normal levels of anti-epilectically acting GABA, but can be attributed to cysteine and glycine, aminoacids linked to GSH. PMID- 2892287 TI - Biochemical changes in the rat after chronic thioacetamide intoxication. AB - Male Wistar rats were given drinking water ad libitum with 0.075% thioacetamide (TAA) for 4 weeks. TAA treatment did not affect serum aminotransferase activities and total bilirubin content. The activities of 5'-nucleotidase, K+, Na+- and Mg2+ adenosine triphosphatases in liver plasma membrane preparations were strongly depressed, while that of gamma-glutamyl transferase was considerably increased. A decline in liver microsomal cytochrome P-450 and cytochrome b5 concentrations was also recorded. In contrast, the content of reduced glutathione in liver homogenate supernatant (9000 g) increased about 2-fold. As plasma membrane associated enzymes seem to be exclusively affected, the liver plasma membrane could be involved in the pathogenesis of the TAA-induced precirrhotic liver changes. PMID- 2892288 TI - Occurrence of palytoxin in the trigger fish Melichtys vidua. AB - The trigger fish Melichtys vidua, collected at Pingelap Atoll in Ponape in The Federated States of Micronesia, contained a potent toxin in the viscera, flesh, and digestive tracts with contents. The toxic principle appeared identical to palytoxin on the basis of toxicity and chromatographic properties. PMID- 2892289 TI - [Dental splinting in acute trauma in children]. PMID- 2892290 TI - Transplantation of DLA-compatible and incompatible fetal liver hematopoietic cells in dogs. AB - Requirements for sustained engraftment of fetal liver hematopoietic stem cells were evaluated in 45 dogs. Pretransplant preparative treatment with total-body irradiation, 14.7 Gy, permitted engraftment of DLA-compatible fetal liver cells. Radiation alone was inadequate in DLA-haploidentical or DLA-mismatched transplants; none of 5 dogs had engraftment. Addition of cyclosporine facilitated engraftment. The combination of 14.7 or 16.1 Gy total-body irradiation (TBI) and cyclosporine allowed engraftment in 15 of 19 (78%) dogs receiving DLA histoincompatible grafts and 11 Gy TBI plus cyclosporine allowed engraftment in 4 of 10 dogs. Restoration of granulopoiesis and thrombopoiesis was rapid; recovery of lymphocytes was relatively delayed, especially in recipients of incompatible fetal liver cells. Cumulative one-year survival was decreased in recipients of incompatible grafts due to early posttransplant infections. These data suggest that fetal liver transplantation is a potential approach in patients who lack an HLA-identical donor for bone marrow transplantation. PMID- 2892291 TI - Facilitation of allogeneic bone marrow transplantation by a T cell-specific immunotoxin containing daunomycin. AB - Daunomycin coupled via an acid-sensitive spacer to monoclonal Thy-1.2-specific antibody was used to purge T lymphocytes from a 1:1 mixture of murine C57BL/6J bone marrow and spleen cells prior to engraftment in fully allogeneic, irradiated BALB/c recipients. Treatment of bone marrow with the immunotoxin at a concentration used for purging had no effect on the viability of committed hematopoietic progenitor or multipotent stem cells. All of the recipients of purged bone marrow were at least 80% chimeric for donor peripheral blood cells and none developed graft-versus-host disease. Out of 50 chimeras, 49 were still alive more than 200 days posttransplantation. The chimeras were shown to be tolerant to donor tissue as tested by mixed lymphocyte reactivity, cell-mediated cytotoxicity, and skin grafting. The same tests revealed full immunocompetence of chimeras to third-party alloantigens. In vivo IgM and IgG antibody responses to sheep red blood cells were similar in magnitude in allogeneically and syngeneically reconstituted mice. PMID- 2892292 TI - Specific allelic variation among linked HLA class II genes. AB - Locus-specific oligonucleotides have been used as probes to detect polymorphic alleles for the HLA genes DQ beta, DQ alpha, DX alpha, and DO beta. These genes lie between the HLA DR and DP genes on chromosome 6, a region frequently implicated in intra-HLA recombination. In order to distinguish among these highly homologous HLA class II genes, we have identified sequences in the coding regions that are locus specific and have synthesized short oligonucleotide probes corresponding to these regions. We have used these probes in a gel hybridization procedure to analyze restriction-enzyme-digested genomic DNA and to assign polymorphic bands to a particular locus. Taq I-digested DNA hybridized with a DQ beta-specific probe detects a single band per haplotype. The size of this band corresponds precisely to the expressed DQ beta gene and distinguishes among the serologically defined DQ alleles, providing a rapid method for genomic DQ typing. Similar analysis with an oligonucleotide probe specific for DX alpha, the nonexpressed alpha gene in the DQ subregion, detects 2 DX alleles, and hybridization with an oligonucleotide specific for the newly described DO beta gene detects 2 alleles at DO beta. Heterogeneity in linkage patterns among DQ, DX, and DO genes suggests that frequent recombinational events at multiple intergenic sites contributed to the generation of present-day haplotypes. One such recombinational event was identified directly in a family with serologically HLA-identical siblings, in which genomic analysis indicated a parental recombination event mapping between DR and DX, which correlated with unexpected alloreactivity. PMID- 2892293 TI - Effect of low-temperature culture on the survival of intratesticular rat islet allografts. PMID- 2892294 TI - Impairment of hemopoiesis in human allografts. PMID- 2892295 TI - Positive bethanechol supersensitivity test in neurologically normal patients. AB - A positive bethanechol supersensitivity test (BST) usually indicates neuropathic detrusor areflexia and warrants neurologic correlation. Seven females, average age thirty-three years, with straining to void and high residual urines, had detrusor areflexia, with a borderline or positive BST, ranging from 19 cm water to 55 cm H2O change in intravesical pressure after 5 mg of subcutaneous bethanechol. However, all patients had a normal neurologic workup, even though 2 patients had insignificant spina bifida occulta. Two of the patients also had prior pelvic surgery, 1 of whom was azotemic, and 4 of the patients had psychosocial problems; factors reported to be associated with a false positive BST. The positive BST is not diagnostic of neurogenic detrusor areflexia because of the many variables that can influence the test. Therefore, the bethanechol supersensitivity test should be interrupted in light of the complete neurourologic evaluation. PMID- 2892296 TI - [A complicated variant of cryptorchism in a child]. PMID- 2892297 TI - Incidence of outdated ipecac in the home. PMID- 2892298 TI - Beta-blockade for acute theophylline-induced seizures. PMID- 2892299 TI - Phenotypic changes in mast cells proliferating in the rat lung following infection with Nippostrongylus brasiliensis. AB - Numerous mast cells appear in rat pulmonary granulomas associated with infection by the nematode Nippostrongylus brasiliensis. The kinetics and histochemical characteristics of these mast cells were studied and compared with those of intestinal mucosal mast cells. The number of lung mast cells showed a distinct increase 2 weeks after injection and then gradually decreased. In a study using bromodeoxyuridine (BrdU), which is incorporated into cellular DNA at the S-phase, mast-cell labeling was highest 12-13 days after infection, and returned to the normal level 21 days after infection. This indicates that lung mast cells proliferate for only a short time. Intestinal mucosal mast cells showed a similar pattern. A parallel increase in globule leukocytes in the bronchus and trachea was also observed. The proliferating lung mast cells in the early period were stained with alcian blue but were negative for berberine and avidin-biotin peroxidase complexes (ABC). In a lung extract, type II protease, which has been reported to be confined to mucosal mast cells, increased until the 14th day, and decreased thereafter. This indicates that lung mast cells, at least in the initial stage of proliferation, are similar to intestinal mucosal mast cells in terms of their cell kinetics and histochemical characteristics. However, histochemical studies of mast cells at a later stage of infection showed a different result. After 12 weeks of infection when the mast-cell density was still high, almost all the lung mast cells became positive with berberine and/or ABC, both of which are supposed to be bound to heparin within mast cell granules.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892300 TI - Lectin histochemistry and ultrastructure of feline kidneys from six different storage diseases. AB - We have compared the pattern of lectin staining with the ultrastructural features of kidneys from normal cats and 19 cats with 6 different lysosomal storage diseases. The diseases studied include GM1 and GM2 gangliosidosis, mucopolysaccharidosis (MPS)-I and MPS-VI, sphingomyelin-lipidosis (i.e., Niemann Pick disease) and mannosidosis. Ten different biotinylated lectins were used as histochemical probes for carbohydrate residues and avidin-biotin-peroxidase complex as visualant. Concanavalia ensiformis agglutinin (Con A) stained mesangial cells in all storage diseases but GM1, epithelial cells in sphingomyelin-lipidosis and mannosidosis, endothelial cells in GM1 and mannosidosis and Bowman's capsule cells in all but GM2. Griffonia simplicifolia agglutinin I (GS-I) stained the glomerular endothelium in all six diseases, but not in control kidneys. Ricinus communis agglutinin-I (RCA-I) stained the glomerular epithelium only in GM1 and MPS-I. Succinylated wheat germ agglutinin (SWGA) stained the glomerular endothelium and epithelium in mannosidosis, and the glomerular epithelium and Bowman's capsule in MPS-I. Ultrastructure studies demonstrated an accumulation of oligosaccharides in cases of mannosidosis and GM1 gangliosidosis, a mixture of oligosaccharides and lipids in MPS-I, MPS-VI and GM2 gangliosidosis and only lipid storage in sphingomyelin lipidosis. These studies show that morphologic and histochemical changes are manifested in some kidney cell types in lysosomal storage diseases, even though the enzyme deficiency occurs in all cell types. Furthermore, we show that the nature of the undegraded stored material is complex and that other factors, such as rate of membrane turn over, membrane composition, and cell function may influence the amount and nature of the "stored" material. PMID- 2892302 TI - Effects of retinoic acid on the growth and morphology of hamster tracheal epithelial cells in primary culture. AB - Hamster tracheal epithelial cells were grown in primary culture on a collagen gel substrate in hormone-supplemented serum-free Ham's F12 medium with 10(-8) M retinoic acid (RA+), or without retinoic acid (RA-). On days 1 and 2, the colonies were composed of large (secretory) cells and lesser numbers of small (basal) cells; ciliated cells were rare. At these times, cell number, thymidine incorporation, and total labelling indices (small and large cells, combined) were similar in RA+ and RA- cultures, but the large cells became flat in RA- medium on day 2. On days 3-5, thymidine incorporation and total labelling indices were less in RA- than RA+ cultures, and on days 4-6, cell numbers were decreased in RA- cultures. On day 3, the large cells of the RA- colonies had flattened further and clusters of small basal cells had formed. On day 4, the RA+ colonies were composed of densely-packed cuboidal secretory cells, small basal cells were inconspicuous; the total labelling index was about 27%. The RA- colonies were composed of large flat secretory cells and numerous small basal cells which were clustered in groups; the total labelling index was about 7%. Since large and small cells could be discriminated by size in RA- colonies, a labelling index was generated based on cell size. On days 2, 3 and 4, the labelling index of the small basal cells in the RA- colonies was 44%, 43% and 24% respectively, whereas the labelling index of the large secretory cells fell rapidly over the same period (56%, 14% and 2%). On days 5 and 6, the cuboidal secretory cells in the RA+ cultures had differentiated further and the cells were stratified focally. Some new ciliated cells had formed on day 6. In RA- cultures, mucous granules were not observed in the large flat cells and ciliated cells were not seen. The total labelling indices were 11% and 0.35% in RA+ cultures, and 0.5% and 0.25% in RA- cultures on days 5 and 6, respectively. The study shows that the target cell for vitamin A in the hamster tracheal epithelium is the secretory (mucous) cell. When retinoic acid was deficient, the secretory cells flattened and their capacity to divide was greatly diminished. Since the basal cells continued to replicate when the secretory cells did not, the population density of the basal cells increased disproportionally, which could be interpreted erroneously as a "basal cell hyperplasia".(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2892301 TI - Oxygen derived radicals related injury in the heart during calcium paradox. AB - The effects of oxygen-derived radical scavengers (ODRS) on the heart was investigated during the calcium paradox. Perfusion with Ca2+-free medium caused cell separation at the intercalated discs and changes in the endothelial cells. Upon Ca2+ reintroduction, a massive cell damage occurred. The cytosolic enzyme, creatine phosphokinase (CPK), was released in large amounts (p less than 0.001). The tissue adenosine triphosphate (ATP) was reduced to 3.7 mumol/g dry weight from the control value of 21.6 mumol/g dry weight and tissue Ca2+ content was increased threefold. The treatment with superoxide dismutase (SOD) and catalase (CAT) increased percentage of normal cells (62.2%) compared to nontreated Ca2+ paradox group (0.2%) and caused negligible leakage of CPK. Tissue ATP was preserved (p less than 0.03), and Ca2+ content was also reduced in the hearts treated with SOD and CAT (p less than 0.03). The cell membranes and vascular endothelium were well preserved in the hearts treated with SOD and CAT. Boiled SOD and CAT administered were totally ineffective. It is suggested that oxygen active species may have a role in the Ca2+ paradox injury. PMID- 2892303 TI - Level of Opisthorchis infestation and carcinogen dose-dependence of cholangiocarcinoma induction in Syrian golden hamsters. AB - The relationship between different levels of liver fluke, Opisthorchis viverrini infestation and dimethylnitrosamine (DMN) dosage in the induction of cholangiocarcinomas was investigated in Syrian golden hamsters. Two hundred and eighty male, weanling animals were divided into 4 groups: Group 1 served as untreated controls; group 2 received O. viverrini metacercariae only at levels of 100, 50, 25 or 12 per animal; group 3 received DMN only at doses of 12.5, 6.25 or 3.125 ppm; group 4 received various combinations of metacercariae and DMN. Only 2 of 17 animals (12%) in group 3 receiving 12.5 ppm had detectable tumours and no neoplastic lesions were seen in the 6.25 and 3.125 ppm DMN subgroups or in parasite alone or untreated control hamsters. In contrast, high carcinogen and parasite dose-dependent yields of cholangiocarcinomas (incidences up to 93%) and putative preneoplastic cholangiofibrotic lesions were observed in group 4. Thus the results indicate clear dose-dependent synergistic effects for the two agents and reveal the crucial importance of the presence of parasite, even at levels as low as 12 metacercariae, for DMN induction of bile duct carcinogenesis. PMID- 2892304 TI - Development of intracytoplasmic lumina in diethylnitrosamine-induced tracheal papillomas of Syrian golden hamster. A light and electron microscopical study. AB - Tracheal papillomas in the Syrian golden hamster were induced with diethylnitrosamine (DEN). Intracytoplasmic lumina filled with mucus were studied by light and electron microscopy. The sequence of lumen genesis is described ultrastructurally. Mucus substances in the center of intracytoplasmic lumen are presumed to be condensations of cell coat macromolecules. The intracytoplasmic lumen is discussed as a common feature of the adenoid component in epithelial neoplasms. PMID- 2892305 TI - Light and electron microscopical demonstration of c- erB-2 gene product-like immunoreactivity in human malignant tumors. AB - C-erbB-2 is a human protooncogene homologous with the well-known c-erbB. Genes and gene products of the EGF receptor and c-erbB are known to be closely related and to be closely homologous in their intracellular domain. Inspection of the deduced amino acid sequence suggested that the c-erbB-2 gene encodes a receptor for a yet unidentified growth factor. An immunohistological study was performed by introducing an antibody raised in the rabbit by immunization with a synthetic peptide corresponding to a part of the intracytoplasmic domain of predicted gene product. Specimens from 13 normal human organs, fresh frozen tissue from 41 surgically excised human malignant tumors and eight cell lines maintained in nude mice were studied. Positive staining was found in 4 of the 41 (9.8%) malignant tumors. All of the positive tumors were adenocarcinomas and two adenocarcinoma cell lines were also positive. Amongst the normal human tissues, epithelial cells in stomach, small and large intestine were faintly stained. When the positively stained cell lines were studied by immunoelectronmicroscopy, the reaction was most prominent in the membrane of microvilli, but part of the nuclear membrane, the endoplasmic reticulum and the outer cell membrane were also stained. DNA and mRNA blot assays, as well as our immunoprecipitation test, revealed that immunohistologically positive cell lines bore amplified c-erbB-2 DNA, c-erbB-2 mRNA and 185 kD protein which is supposed to be the gene product, while negative cell lines did not. PMID- 2892308 TI - Cytoplasmic microvesicles in chromophobe cell renal carcinoma demonstrated by freeze fracture. AB - In the chromophobe cell type of renal carcinoma, cytoplasmic microvesicles (frequently with "inner vesicles") demonstrable by transmission electron microscopy are one of the most important diagnostic features. The present paper reports on these microvesicles in freeze fracture replicas. Their diameter is mainly between 140 and 300 micron, but smaller and very much larger vesicles may also occur. The vesicle membrane is devoid of, or contains only scanty intramembranous particles. Cytoplasmic invaginations, probably the precursors of "inner vesicles" can also be detected. Connections with the agranular endoplasmic reticulum, mitochondria or other cell components could not be documented. Larger vacuoles limited by a membrane and containing large numbers of microvesicles have been interpreted as autophagic vacuoles. In freeze fracture replicas, there are marked differences between the chromophobe cell and the clear cell type of renal carcinoma, providing further evidence that the chromophobe cell type is a distinct entity. PMID- 2892307 TI - Stimulation of pituitary corticotrophs in the rat--ultrastructural studies. AB - The ultrastructural changes occurring in the corticotrophs of adult male and female Sprague-Dawley rats at 2 and 6 weeks after bilateral adrenalectomy were assessed on both a qualitative and quantitative basis. Qualitative changes were similar to those previously described but at both time points, female rats showed more marked changes than males. Corticotroph hypertrophy reached a plateau in male animals between 2 and 6 weeks, but continued to increase in females. There was an increase in mean granule diameter in both sexes at 2 weeks after adrenalectomy. The changes induced by the daily administration of CRF for 2 weeks by intraperitoneal injection were also examined in male rats. CRF induced corticotroph hypertrophy at both 25 micrograms/Kg and 50 micrograms/Kg body weight and increased the granule content. The addition of vasopressin (VP) to the higher dose of CRF induced a further increase in cell area and reduction in granule content. Low dose CRF was associated with an increase in mean granule diameter, whereas a decrease was seen after high dose. PMID- 2892306 TI - A semiautomatic image analyzing system based on an APPLE II or IIe personal computer. AB - A new semiautomatic image analyzing system based on an APPLE II or IIe personal computer is described. The configurations of the hardware and software are extensively explained. The possibilities of applying the system are demonstrated by different examples taken from various projects in biological research and clinical pathology. The system is designed to fulfil the following requirements: (1) stepwise realization as a unit-by-unit system according to individual needs and interests, (2) acquisition and calculation of morphometric parameters, (3) provision of solutions for the greatest possible number of given problems in clinical and experimental pathology, (4) direct connection of the system to host computers for on-line data transfer and evaluation, and (5) optimum cost-benefit ratio by manifold application possibilities for the individual hardware and software elements. The advantages of the unit-by-unit system with personal computers outweigh in many respects the disadvantages (for example, increased file handling and limited capacity) in comparison with the closed automatized image evaluation system, particularly with regard to costs, flexibility and compatibility. The system is being further developed in collaboration with Kontron Bildanalyse GmbH, Eching/Munich, FRG. PMID- 2892309 TI - Effect of long-term inhibition of hydroxy-methylglutaryl coenzyme A reductase by mevinolin on the zona fasciculata of rat adrenal cortex. A combined morphometric and biochemical study. AB - The effects of a 7-day infusion with mevinolin, a potent competitive inhibitor of hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase, on the adrenal zona fasciculata were examined in normal and dexamethasone/ACTH-treated rats. In both groups of animals, the drug caused a lowering in plasma and intra-adrenal cholesterol concentrations, as well as a slight decrease in the blood level of corticosterone. Morphometry of zona fasciculata cells showed that specific mevinolin-induced changes (i.e. those occurring in both groups of rats and therefore not due to enhanced release of ACTH following decrease in circulating corticosterone) are severe lipid-droplet depletion and a conspicuous increase in smooth endoplasmic reticulum (SER) and peroxisomes. The hypothesis is discussed that these morphological changes express a compensatory response of zona fasciculata cells to counteract the mevinolin-induced inhibition of cholesterol synthesis in both liver and adrenal cortex. PMID- 2892310 TI - The influence of fixation on the morphology of mouse epidermis. A light and electron microscopical study with special reference to "dark cells" and epidermal carcinogenesis. AB - Different opinions exist on the normal ultrastructure of the epidermis including the significance of so-called basal dark cells. Thus, the dark cells are still assumed to be key elements in experimental skin carcinogenesis. We therefore explored the effects of tissue fixation on the ultrastructure of the epidermis. Untreated normal hairless mouse skin was processed for transmission electron microscopy with two different sets of fixatives, applied either by perfusion immersion or immersion fixation only. The morphology of both the basal and the lower suprabasal layers of the epidermis, including the extracellular space, the shape and volume of the cells, their electron density, and the organisation of some of the organelles, were profoundly affected by the choice of fixatives. The non-keratinocytes showed comparable changes, including the appearance of a dark phenotype. The incidence of small electron-dense keratinocytes (dark cells) and the nature of their ultrastructure changed markedly with the fixation procedure. We were not able to identify undifferentiated dark cells. The pattern of changes and the quality of the morphological picture were almost unaffected by the mode of fixation. The upper suprabasal and the cornified layers appeared to be more or less unaltered by the change in fixatives and the method of application. The vehicle osmolality of the primary fixative was found to be mainly responsible for the ultrastructural appearances. A low vehicle osmolality may be responsible for the occurrence of the dark cell phenomenon, by inducing swelling artefacts of many cells with compression of some neighbouring cells. PMID- 2892311 TI - The use of the anti-factor VIII method on trephine biopsies of the bone marrow for the identification of immature and atypical megakaryocytes in myeloproliferative diseases and allied disorders. A morphometric study. AB - A morphometric analysis was performed on trephine biopsies of the bone marrow to identify atypical megakaryocyte proliferation following PAS staining and the immunohistological demonstration of factor VIII. This study includes nine patients with a megakaryoblastic crisis in chronic myeloid leukemia (CML), four with acute megakaryoblastic leukemia (AM) and three with myeloid dysplasia later evolving into overt acute leukemia. Comparison and statistical evaluation of the PAS reaction with anti-factor VIII staining reveals that the latter technique not only facilitates the recognition of immature and abnormal megakaryocytes, but leads to a significantly increased count for all megakaryocytic elements in the bone marrow. Thus our retrospective investigation of routinely processed and paraffin-embedded trephine biopsies shows that the diagnosis of a megakaryoblastic crisis in CML as well as AM may be easily established with the aid of the anti-factor VIII method. In all cases of megakaryoblastic proliferation in CML and AM, the appearance of blasts was associated with moderate to pronounced myelofibrosis which could be also determined by morphometry. PMID- 2892312 TI - Major rearrangement of cellular DNA in the vicinity of integrated polyomavirus DNA. AB - The Cyp cell line was produced by transforming mouse embryo cells at the restrictive temperature with an early thermosensitive mutant of polyomavirus (Py). Transfer of Cyp cells to the nonrestrictive temperature causes excision to occur at a single chromosomal site carrying viral DNA, and leads to the production of infectious virus. We have attempted to elucidate the recombination event that occurred during the integration of Py DNA in this inducible line. Physical characterization of two recombinant DNAs-one selected from a genomic library of normal mouse DNA and the other constructed from the unoccupied allele of the Cyp integration site-indicates that generation of the Cyp line has involved the joining of not only viral DNA to a cellular alpha site, but also the cellular alpha site to a cellular alpha site to cellular beta site. Hence, previously described hybrid excision products from the Cyp line were made of mouse DNA segments representing two distinct cellular sites. The alpha-beta joining may play a role in the expression of integrated Py DNA. PMID- 2892313 TI - A functional role for intermediate filaments in the formation of frog virus 3 assembly sites. AB - During the course of frog virus 3 (FV3) infection in baby hamster kidney 21 (BHK) cells, vimentin-type intermediate filaments reorganize to surround the virus's cytoplasmic assembly sites. To determine whether the association between vimentin filaments and viral assembly sites has a functional role in the virus life-cycle, we treated cells with the antimicrotubule drugs taxol or colchicine, or injected them with monoclonal antivimentin antibodies prior to FV3 infection. Each of these reagents caused the collapse of the normally extended BHK intermediate filament system. In the case of taxol-treated or antivimentin-injected cells, the collapsed vimentin filaments were unable to reorganize around the newly forming viral assembly sites. The viral assembly sites that did form were aberrant and there was a significant reduction in the number of mature virions present. Colchicine, which also caused the collapse of vimentin filament organization, did not block the reorganization of vimentin filaments in response to viral infection and viral assembly sites appeared normal. These results suggest that intermediate filaments play an important role in maintaining the structural and functional integrity of FV3 assembly sites. PMID- 2892314 TI - [T-cell leukemia/lymphoma in adults--a human tumor of probable viral origin]. PMID- 2892315 TI - [Pathogenetic mechanisms of the spread of the lesion focus in myocardial infarct and measures for its limitation (a review of the literature)]. PMID- 2892316 TI - [Mechanism of the stimulation of immunogenesis by antitumor preparation 6--a plant antibiotic]. PMID- 2892317 TI - Aspects of human T-cell lymphotrophic virus type 1--associated diseases in Jamaica. PMID- 2892318 TI - [Status of eye movement data in the microanalysis of cognitive processes]. PMID- 2892319 TI - [Figure recognition and reproduction in hearing, hard of hearing and deaf children: an empirical analysis]. PMID- 2892320 TI - [The concept of hormones and their criteria in modern endocrinology]. PMID- 2892321 TI - [The physiological sciences in the USSR in 1917-1987 (a short chronicle of events)]. PMID- 2892323 TI - [Neurogenic arterial hypertension in monkeys: neurohormonal mechanisms, prevention and treatment]. PMID- 2892322 TI - [Physiological mechanisms of biological rhythms]. PMID- 2892325 TI - [Anaerobic spore formers in commercial spices and ingredients for infant food]. AB - Anaerobic spore-formers can cause food intoxication. Clostridium (Cl.) perfringens type-A strains are mainly involved. In addition to the original contamination of food, e.g., meat or milk, ingredients such as spices or meat extracts are the main source and low numbers of clostridia are present (i.e., up to 10(2) cells/g). At present, information about the quantitative ecology of clostridia is incomplete; therefore 115 commercial food products were investigated (spices: n = 70, meat extracts: n = 15, instant foods: n = 30). For the detection of low numbers of clostridia (less than 10(3)/g), the most probable number (MPN) technique was used. For the detection of higher numbers (greater than 10(3)/g) a cultivation method in solid media was developed. The mesophilic sulphite-reducing clostridia spores were detected by the pour-plating method with overlayer. Twenty-one of the 70 commercial spices, 7 of the 30 specimen of instant food and 12 of the 15 meat extracts were clostridia-positive. The low counts ranged between 3 X 10(0) and 10(3) cells/g, in most cases (2/3) in the range 10(1)/10(2)/g. Only in 6 cases were more than 10(3) clostridia/g detected. Most of those isolated were identified as Cl. perfringens (46 of 73 isolates). Only in meat extracts did clostridia species other than Cl. perfringens strains predominate. Three of the 23 Cl. perfringens strains proved to be heat-resistant. A hydrated meat extract originally contaminated with low numbers was tested in a pilot study for the enrichment of clostridia. This extract showed an increase of up to 10(7) cells/ml after a 24-h incubation period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892324 TI - Repellent soap for use against malaria vectors in Papua New Guinea. PMID- 2892327 TI - Growth curves of Clostridium perfringens in Schaedler and brain heart infusion broths. AB - Four Clostridium perfringens strains recovered from clinical specimens, four strains obtained from faecal specimens of healthy adults, and control strain ATCC 13124 were inoculated into Schaedler and Brain Heart Infusion broths, respectively, and incubated anaerobically at 35 degrees C for 24 h. The exponential growth phase usually lasted from 2 to 6 h following inoculation; the generation times averaged 23 min at 2 to 4 h and 27 min between 4 and 6 h of incubation. The early stationary growth phase (generation time between 6 and 8 h = 89 min) was reached at 8 h following inoculation. All strains displayed essentially identical in vitro growth rates, even though they differed in murine virulence. PMID- 2892326 TI - Enzyme activities of the strains belonging to family Leptospiraceae detected by the API ZYM system. AB - A total of 32 strains of the family Leptospiraceae (23 strains of Leptospira interrogans, 6 strains of Leptospira biflexa, 2 strains of Leptonema and 1 strain of Leptospira parva) were examined for enzyme activities using 89 substrates (API ZYM system). More than 90% of the strains belonging to the family Leptospiraceae possessed strong activities of beta-D-galactosidase, beta-D-glucosidase and 5 esterases (C5, C6, C8, C9 and C10). More than 90% of the strains belonging to the genus Leptospira, except L. parva, had strong activities of L-lysine arylamidase and alpha-L-glutamate arylamidase. L. biflexa strains, except serovar andamana, were different from the other strains examined in that they possessed glycyl glycine arylamidase, glycyl-phenylalanine arylamidase and L-tryptophan arylamidase. L. biflexa strains, except andamana, L. parva and Leptonema strains possessed strong activities of glycine arylamidase and leucyl-glycine arylamidase. Two strains of the genus Leptonema were different from the strains belonging to the genus Leptospira in that they possessed strong activities of beta-D-lactosidase. L. parva lacked alpha-D-galactosidase which other strains belonging to the family Leptospiraceae possessed. Dendrogram analysis revealed that strains belonging to the family Leptospiraceae were divided into 4 groups. The first group consisted of all strains belonging to L. interrogans and serovar andamana of L. biflexa; the second group consisted of the remaining 5 serovars of L. biflexa; the third group consisted of the genus Leptonema; and the fourth group consisted of only L. parva. PMID- 2892328 TI - [Possibilities for neurotransmitter correction in parkinsonism (a review)]. PMID- 2892329 TI - Hantavirus nephropathy, an unrecognized cause of transient acute renal failure in Belgium. PMID- 2892330 TI - [Hantavirus nephropathy in Belgium: description of 2 new cases originating in southern provinces]. PMID- 2892331 TI - [Hantavirus nephropathy: apropos of 4 cases diagnosed in south Hainaut]. PMID- 2892332 TI - Plasma levels of growth hormone-releasing hormone and somatostatin in response to a mixed meal and during sleep in children. AB - Following a mixed meal, plasma levels of GHRH, GH, SRIH and insulin were measured in 7 prepubertal children with constitutional delay of growth and adolescence (CDGA) and in 3 children with proven GH-deficiency which responded to GHRH injection. In children with CDGA, plasma levels of GHRH increased between 60 and 120 min (10.1 +/- 1.2 ng/l vs 25.5 +/- 4.4 ng/l; P less than 0.01). Although no GH increase occurred in patients with GH-deficiency, their plasma GHRH increases were comparable to those in CDGA children. No time relationship was present between circulating GHRH and GH, SRIH, or insulin, nor was there any correlation between their integrated hormone response areas. Sleep-induced plasma GHRH, GH and SRIH values were determined in 10 prepubertal children with CDGA. Spontaneous variations of plasma GHRH and GH values occurred with no temporal or quantitative relationship. SRIH values did not change during nocturnal sleep. In one child with GH-deficiency, comparable GHRH plasma fluctuations occurred, although GH values were all below 1 microgram/l. Our results support the concept that circulating GHRH does not only represent hypothalamic GHRH, but derives mainly from extrahypothalamic sources, possibly from the gastrointestinal tract. PMID- 2892333 TI - Clinical use of somatostatin analogues (Sandostatin, SMS 20l-995). Proceedings of a symposium. Amsterdam, November 14, 1986. PMID- 2892334 TI - Clinical and pathophysiological aspects of somatostatin and the gastrointestinal tract. AB - Somatostatin is present in the gastrointestinal tract in appreciable amounts. The highest concentrations of the polypeptide are found in the stomach, the upper small intestine, and the pancreas. Within the gastrointestinal tract, somatostatin inhibits various functions, including endocrine and exocrine secretion, motility, blood flow, absorption, and growth. The polypeptide regulates these functions by endocrine, paracrine, neurocrine or luminal mechanisms. Abnormalities of endogenous somatostatin have been implicated in several gastrointestinal disorders, including the somatostatinoma syndrome, antroduodenal D-cell hyperplasia, peptic ulcer, obesity, and liver cirrhosis. Because of its potent inhibitory effects, somatostatin or somatostatin-analogues have been used as therapeutic agents in various clinical conditions, such as upper gastrointestinal haemorrhage, endocrine pancreatic tumours, gastrointestinal and pancreatic fistulas, pancreatitis, secretory diarrhoea, and dumping syndrome. The recent availability of the synthetic long-acting somatostatin-analogue SMS 201-995 (Sandostatin) has greatly facilitated the therapeutical application of somatostatin-polypeptides. PMID- 2892335 TI - Clinical evaluation of SMS 201-995. Long-term treatment in gut neuroendocrine tumours, efficacy of oral administration, and possible use in non-tumoural inappropriate TSH hypersecretion. AB - Long-acting somatostatin analogues such as SMS 201-995 (Sandoz) are being evaluated in a wide range of clinical indications, including gut neuroendocrine tumours and acrogemaly. Long-term continuous SMS 201-995 treatment has achieved useful symptomatic improvement in diarrhoea in 4 patients with metastatic VIPomas who had relapsed following previous treatment. Clinical improvement has outlasted suppression of VIP secretion (suggesting an additional direct antisecretory action of SMS 201-995) and has occurred despite expansion of hepatic metastases. In 6 patients with tumours secreting gastrin and/or glucagon, secretion of these peptides was acutely inhibited by SMS 201-995. However, endocrine and clinical responses to chronic treatment have been less consistent. SMS 201-995 is active orally at doses of 4-8 mg and when given thrice-daily to 6 patients with active acromegaly, suppressed mean 24-h growth hormone levels by 51-88%. Despite significantly reduced plasma insulin concentrations, glucose tolerance did not deteriorate. SMS 201-995 was also effective in suppressing thyroid-stimulating hormone (TSH) and thyroid hormone secretion in a patient with mild thyrotoxicosis due to non-tumoural inappropriate TSH hypersecretion. In all cases SMS 201-995 treatment has been well tolerated and has few side-effects. PMID- 2892336 TI - SMS 201-995 and variceal haemorrhage. AB - Sandostatin (SMS 201-995) was evaluated in the treatment of variceal bleeding in 9 patients with liver cirrhosis and portal hypertension who were undergoing injection sclerotherapy following a variceal haemorrhage. SMS 201-995 reduced directly recorded intravariceal pressure by 38%, whereas reductions in the wedged hepatic venous pressure were around 17%. These observations suggest that SMS 201 995 may prove useful in treating bleeding oesophageal varices in the acute situation. Preliminary, promising data are shown in the results of a randomized controlled clinical trial in which SMS 201-995 plus injection sclerotherapy vs injection sclerotherapy are compared in patients with bleeding oesophageal varices. Furthermore, in experimental work associated stimulating effects of SMS 201-995 are shown on the function of the reticulo-endothelial system both in the liver and peripherally. These effects may prove useful by reducing the effects of endotoxaemia and possibly result in arresting further liver damage. PMID- 2892337 TI - Long-acting somatostatin analogue (Sandostatin) reduces late night insulinopenic ketogenesis in diabetic teenagers. AB - Ten diabetic teenagers were admitted into our hospital for two nights, separated by one week. In a double-blind cross-over randomized study they received either 50 micrograms of the new long-acting somatostatin analogue Sandostatin sc or placebo. All patients were between 12 and 16 years of age, C-peptide negative with a duration of diabetes of at least four years. They had either conventional therapy or insulin pump therapy. Insulin doses and diets were kept unchanged. Blood samples were taken half hourly from 17.00 h until 09.30 h the next morning from an indwelling venous catheter. Hormonal and metabolic profiles on the two nights were evaluated by means of a distribution free time sequential co-movement analysis and by the paired Wilcoxon's signed rank test. After Sandostatin was given at 22.00 h, GH levels were significantly suppressed during 4 h. During that period blood glucose was slightly but significantly lower than after placebo. The free-insulin profiles from both nights were very comparable. Co-movement analysis showed a significant correlation between glucose and free insulin variations with a 30-min backward shift of the glucose curve. However, after Sandostatin administration this relation was lost in the period between 22.00 and 07.00 h, indicating a different effect of insulin on glucose levels during the nights Sandostatin was given. Early morning glucose rises were associated with free insulin levels below 20 mU/l. This association was not altered during the Sandostatin nights. Glucagon was not suppressed by Sandostatin except at 120 min after injection, and remained unchanged during the rest of the observation period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892338 TI - A guide to the clinical use of the somatostatin analogue SMS 201-995 (Sandostatin). AB - SMS 201-995 (Sandostatin) is an octapeptide which differs in its action from native somatostatin in four ways: 1) it inhibits GH hormone secretion in preference to insulin secretion; 2) it can be administered subcutaneously or even orally; 3) it is long-acting (t1/2 after sc administration 113 min), and 4) there is no rebound hypersecretion of hormones when the effect of the analogue lingers off. In this paper a guide is offered for the use of Sandostatin in the treatment of acromegaly (after unsuccessful operation and/or radiotherapy) and of metastatic endocrine pancreatic tumours and carcinoids. A dose regimen for these two types of patients is suggested and the adverse reactions which can be expected are summarized. In addition, preliminary data are shown and the limitations are discussed of possible future indications of the analogue in the treatment of cancer, diabetes mellitus and gastrointestinal diseases. PMID- 2892340 TI - Dipeptidyl peptidase IV (DP IV), a functional marker of the T lymphocyte system. AB - Dipeptidyl peptidase IV (DP IV; E.C. 3.4.14.5), a plasma membrane structure of human T lymphocytes has been shown to be an important enzyme in the process of activation and proliferation of lymphocytes. In presence of specific inhibitors and antibodies against DP IV different functions of lymphocytes in vitro were found to be impaired. This holds true for mitogen and alloantigen induced DNA synthesis, immunoglobulin production and secretion, and interleukin-2 as well as interferon-gamma production. Studies of mitogen-induced expression of different activation markers (HLA class II antigen, 4F2, Tac) suggested that one of the functions of DP IV lies in overriding the cell cycle restriction point at G1. These data, together with other features of the DP IV, support the notion that this enzyme plays a key role in the modulation of lymphokine action by X-Pro- or X-Ala-directed limited proteolysis. Moreover the high frequency of DP IV susceptible bonds in different growth factors (e.g. IL-1, IL-2) and other biologically active peptides leads to the speculation that this peptidase is of more general significance to the regulation of cell growth. PMID- 2892339 TI - Long-term treatment of acromegaly with Sandostatin (SMS 201-995). Normalization of most anomalous growth hormone responses. AB - Twelve patients with active acromegaly were treated with the long-acting somatostatin analogue SMS 201-995 (SMS), at a dose of 50 micrograms sc twice daily in the first 2 weeks of treatment and 100 micrograms sc thereafter. Four h after the first injection of SMS, GH levels became normal in 8 of the 12 patients. Basal glucose levels were significantly lower at the 28th day of treatment. This glucose lowering effect was stronger in the diabetic than in the nondiabetic patients. The postprandial rise of insulin levels was reversed by SMS, leading to a more pronounced postprandial rise of glucose, whereas the postprandial secretion of glucagon was also reversed by SMS. The rise of glucose levels during oral glucose loading was similar before and during SMS, despite a strong inhibitory effect of the drug on the insulin rise after glucose loading. Basal TSH levels were not influenced by SMS, the TRH-induced TSH response, however, was significantly blunted. Although the basal PRL levels were significantly reduced by SMS, the TRH-induced PRL rise was similar before and during administration of the analogue. Paradoxical GH responses to TRH disappeared in 7 out of 8 patients during SMS. Paradoxical GH responses to GnRH, however, persisted in 4 out of 4 patients. Paradoxical responses of GH after glucose loading disappeared in 2 out of 2 patients. The GH response after GHRH administration was strongly suppressed by SMS. During long-term treatment (up to 2 years), the GH level obtained within 5 h after the last injection of SMS remained normal in the patients whose GH levels normalized at the first day of treatment. There was a good response of the disease to this treatment, and no serious adverse reactions were observed. We conclude that SMS normalizes most anomalous growth hormone kinetics in acromegaly. The drug offers a new tool in the treatment of this disease. PMID- 2892341 TI - Successful use of isoflurane and vecuronium in a patient with Bartter's syndrome: a case study. PMID- 2892342 TI - Effect of beta-sympathotropic agents on water intake under stress: hunger and new environment. PMID- 2892343 TI - Salazosulfapyridine and metabolites in fetal and maternal body fluids with special reference to 5-aminosalicylic acid. AB - In 7 pregnant women, treated prophylactically with salazosulfapyridine (SASP) 3 g/day, amniotic fluid (16th week, n = 4, maternal and cord plasma (n = 5) and breast milk (n = 3) were analysed for SASP and the metabolites sulfapyridine (SP), acetyl sulfapyridine (Ac-SP), 5-aminosalicylic acid (5-ASA) and acetyl 5 aminosalicylic acid (Ac-5-ASA). Amniotic fluid contained concentrations of SASP, SP and Ac-SP and partly also Ac-5-ASA comparable to those previously found by others, whereas 5-ASA concentrations were very low. The ratios of maternal to cord plasma for all SASP metabolites were about 1:1-1:2, except for 5-ASA, cord plasma being extremely low. In breast milk, only traces of 5-ASA were detected, while Ac-5-ASA was above the plasma level. Only negligible amounts of 5-ASA are thus transferred to the fetus/newborn, which is of significance for the future use of the new non-sulfa-containing 5-ASA preparations during and after pregnancy. PMID- 2892344 TI - Qualitative characteristics of the mechanical response in rat papillary muscles to increase in extracellular calcium concentration. AB - The qualitative characteristics of the inotropic response to increase in extracellular calcium (Cao) were studied in isolated, electrically driven, isometrically contracting rat papillary muscles. All experiments were done in the presence of adrenergic receptor blockers. Cao was increased in a cumulative way by exchanging a small fraction of the incubation solution with a corresponding solution with higher calcium concentration (8 mmol l-1). At any Cao level there was an almost proportional increase in parameters describing different parts of the contraction-relaxation cycle as compared with results at the preceding lower Cao level. Time to peak tension was prolonged at high compared with low Cao levels. The response to increased Cao was very similar to the cyclic AMP (cAMP) independent inotropic response elicited through activation of alpha-adrenergic receptors (alpha-type response, Skomedal et al. 1982) and strikingly different from the cAMP-dependent inotropic response elicited, for example, through activation of beta-adrenergic receptors (beta-type response, Skomedal et al. 1982). As the inotropic response to increased Cao is known to be cAMP-independent (Donges et al. 1977), the present results demonstrate the interrelationship between the regulatory function(s) and the direct effector function(s) of calcium in the myocardium. PMID- 2892345 TI - Bicarbonate secretion by the rabbit duodenum in vivo: effects of prostaglandins, vagal stimulation and some drugs. AB - Duodenal HCO-3 secretion in anaesthetized rabbits was measured by continuous titration of the recirculating luminal perfusate at pH 7.4. The segment under study started 3-4 cm distal to the pylorus and was devoid of pancreatic and biliary HCO-3 secretion. On histological examination the submucosa was seen to contain Brunner's glands, mainly of a mucous type. Duodenum in rabbit secreted HCO3- at a considerably higher basal rate (100-125 mu equiv h-1 cm-1 of intestine) than has previously been found in the rat, cat or dog. The cyclo oxygenase inhibitor indomethacin (20 mg kg-1) reduced the secretion by 30%, while prostaglandin E2 (5-80 microM, luminal) caused a dose-dependent increase. Prostaglandins thus seem to be important in regulation of duodenal HCO3- secretion in the rabbit and may play a role in duodenal protection against acid. Carbachol (1 and 10 micrograms kg-1) and atropine (0.5 and 1 mg kg-1) had no effects whereas hexamethonium (10 mg kg-1) caused a persistent decrease (25%) in secretion. Effects of electrical stimulation of the vagal nerves or injection of the alpha 2-adrenergic agonist clonidine markedly depended on the agent used for anaesthesia. In urethane-anaesthetized animals, clonidine (0.75-75 micrograms kg 1) tended to increase the secretion whereas with nembutal, clonidine (5-150 micrograms kg-1) decreased it significantly. Electrical stimulation of the cervical vagal nerves decreased the HCO3- secretion in urethane-anaesthetized animals but had no significant effect during nembutal anaesthesia. The responses in the nembutal-anaesthetized rabbit are similar to those previously observed in the cat, rat or dog. PMID- 2892346 TI - Functional alpha-adrenoceptors in human atrial preparations in the presence of beta-receptor blockade. AB - Inotropic effects via cardiac alpha-adrenoceptors were studied in electrically driven auricular strips (1 Hz, 37 degrees C) from patients treated with beta blockers for months prior to open heart surgery. Marked alpha-mediated positive inotropic effects were demonstrated with adrenaline (A), noradrenaline (NA) and phenylephrine (PHE) in the presence of beta-blocker and with blockers of the muscarinic receptor and of the neuronal and extraneuronal uptake mechanisms for the catecholamines. In the presence of approximately 10(-6) M propranolol the maximal effects as well as the potencies (pD2-values) for A and NA were not significantly different while higher than for PHE. The alpha 1-blocker, prazosin (10(-6) M), markedly reduced the pD2-values but not the intrinsic activities (alpha-values) for A, NA and PHE in the beta-blocked preparations. Methoxamine, however, induced negative inotropic responses at normal and low frequencies (1, 0.5 and 0.1 Hz) of stimulation, suggestive of non-specific, cardiodepressant effects. Other agonists with alpha-effects in other types of tissue (oxymethazoline, xylomethazoline and clonidine) were without effects on the force and velocity of contraction in the auricular strips under the present experimental conditions. The results show alpha 1-type of adrenoceptor-induced inotropic effects for A, NA and PHE during beta-blockade in human auricular strips, indicating that cardiac alpha 1-receptors may have clinical importance by increasing the inotropy of the human myocardium treated with beta-blocking agents. PMID- 2892347 TI - [Neurotransmitters]. PMID- 2892348 TI - Increased activity of serum gamma-glutamyltransferase in myotonic dystrophy. AB - The activity of serum gamma-glutamyltransferase (gamma-GT) and its determinants were studied in 17 patients with myotonic dystrophy. The gamma-GT activity was elevated in 11 patients and its mean value was five-fold higher than in healthy controls. The increase in gamma-GT could not be explained by factors generally known to result in a misleading elevation of gamma-GT. Most patients with elevated gamma-GT also had one or more other pathological laboratory tests related to hepatic function but none had a clinically significant liver disease. Serum gamma-GT activity was not related to the disability caused by dystrophy or to the level of serum creatine kinase suggesting that the elevation of serum gamma-GT is not an indication of a general cell membrane dysfunction. It is concluded that the increase in serum gamma-GT activity in patients with myotonic dystrophy is due to a real but mild liver involvement, which should be taken into account in the examination of these patients who often complain of gastrointestinal symptoms. PMID- 2892349 TI - Chronic 5-HT2-receptor blockade by ritanserin does not reduce blood pressure in patients with essential hypertension. AB - The selective 5-HT2-receptor-blocking agent ritanserin is an analogue of the antihypertensive agent ketanserin. By evaluating the antihypertensive effects of ritanserin the aim of this investigation was to indirectly elucidate the mechanism of action of ketanserin. Thirteen patients with essential hypertension were treated with placebo and ritanserin, 10 mg b.i.d., in a double-blind, cross over design (4-week periods). At the end of the treatment periods blood pressure as well as plasma concentrations of ritanserin were evaluated for 24 hours. Despite high steady state and peak plasma concentrations of ritanserin the compound did not lower the blood pressure compared with placebo. Since chronic selective 5-HT2-receptor blockade by means of ritanserin did not lower the blood pressure, it is concluded that the 5-HT2 blocking properties of ketanserin cannot alone be responsible for the antihypertensive effects of ketanserin. PMID- 2892350 TI - Catecholamine release after physical exercise. A new provocative test for early diagnosis of pheochromocytoma in multiple endocrine neoplasia type 2. AB - A simple and practical provocative test is needed for early asymptomatic pheochromocytoma, which is a major risk for patients with multiple endocrine neoplasia type 2 (MEN-2). We measured plasma catecholamines before and after submaximal exercise in 26 MEN-2 gene carriers, eight of whom with asymptomatic pheochromocytoma, nine with medullary thyroid carcinoma and 10 after uni- or bilateral adrenalectomy. Seventeen clinically healthy individuals and 11 patients with neurovegetative lability and symptoms mimicking pheochromocytoma served as controls. Plasma adrenaline, noradrenaline and dopamine increased after exercise except for adrenaline after bilateral adrenalectomy. The post-exercise levels of adrenaline and the adrenaline/dopamine ratio were significantly higher in the pheochromocytoma patients compared to the healthy controls and the patients with neurovegetative lability, while the patients with medullary thyroid carcinoma represented an intermediate group with a high probability of developing adrenal tumors. The present method is a physiological test with a high sensitivity and specificity. It is practical and well suited for repeated examinations and seems to be of value for the detection of early pheochromocytoma in MEN-2 patients. Furthermore, the test could be used in the differential diagnosis between pheochromocytoma and neurovegetative lability. PMID- 2892351 TI - [Activity of various enzymes in the mesonephros of human embryos and fetuses]. PMID- 2892353 TI - Current state of medicinal treatment of dysrhythmias. PMID- 2892352 TI - Metabolic effects of alcohol in chronic hepatopathies. PMID- 2892354 TI - Placental sulfatase and its importance for the prenatal diagnosis of ichtyosis. PMID- 2892355 TI - The cell-mediated and humoral responses to influenza virus infection in the mouse lung. PMID- 2892356 TI - IgA protease in Entamoeba histolytica trophozoites. PMID- 2892357 TI - Antiamoebic properties of human colostrum. PMID- 2892358 TI - Regulation of the IgA immune response in peripheral blood and in tonsillar lymphocytes from patients with IgA nephropathy. PMID- 2892359 TI - Induction of secretory IgA responses to protein antigens. PMID- 2892360 TI - Intragastric inoculation with an E. coli pilus attachment factor (AF/R1) protects against subsequent colonization by an enteropathogen (E. coli strain RDEC-1). PMID- 2892361 TI - Glycoconjugate receptors for bacteria attaching to mucosal sites: examples for Escherichia coli and Streptococcus pneumoniae. PMID- 2892362 TI - Psychotropic effects of non-psychotropic drugs. PMID- 2892363 TI - Mechanism of cell invasion by Trypanosoma cruzi: importance of sialidase activity. AB - The sialidase activity of trypomastigotes of Trypanosoma cruzi and its relationship to the ability of different stocks of the organism to infect cultured cells was examined. Sialidase activity in lysates of trypomastigotes was confirmed and shown to be present in organisms of four different stocks of T. cruzi. In addition, sialidase activity was detected in sera of mice acutely infected with organisms of each of the stocks of T. cruzi examined. Erythrocytes from these mice were agglutinated by peanut lectin, suggesting sialidase activity in vivo. Treatment of normal mouse peritoneal macrophages with sera from acutely infected mice resulted in an increased capacity of the cells to internalize blood trypomastigotes. IgM or IgG antibodies specific to T. cruzi were not detected in the sera displaying sialidase activity. Treatment of parasites and/or normal mouse macrophages with Vibrio cholerae neuraminidase, however, had little effect in the rate of internalization of parasites. Treatment of L 929 mouse fibroblasts with neuraminidase reduced significantly the rate of infection of the cells with blood trypomastigotes. Anti-sialidase activity developed and was detected in sera of infected mice and humans, suggesting that the neuraminidase activity of the parasite may play a significant role in the invasion of host cells only during the initial phase of the infection. PMID- 2892364 TI - Trypanosoma (Nannomonas) congolense: properties of hexokinase and phosphofructokinase from cultured procyclic trypomastigotes and bloodstream forms. AB - The distribution and kinetics of two key glycolytic enzymes hexokinase (HK) and phosphofructokinase (PFK) were studied in animal-infective bloodstream forms (haematozoic trypomastigotes) and uninfective procyclic forms (insect trypomastigotes) of Trypanosoma congolense. The results show that in both forms of T. congolense HK and PFK are particulate and are probably localized in a membrane-delimited organelle, the glycosome. Hexokinases of bloodstream and procyclic forms of T. congolense are kinetically similar with respect to their affinity for glucose and ATP, the apparent Km for glucose being within the range, of 91 microM to 100 microM and that for ATP, 65 microM to 91 microM. Phosphofructokinase of both forms responds to its substrate in a complex manner: a plot of initial velocity versus substrate concentration displays intermediary plateau regions. PMID- 2892365 TI - Trypanosoma congolense: differentiation to metacyclic trypanosomes in culture depends on the concentration of glutamine or proline. AB - The effect of glutamine on the number of metacyclic trypanosomes produced in insect form cultures of Trypanosoma congolense TREU 1457 was investigated. When cultured in the absence of glutamine, trypanosomes did not develop to metacyclic forms. While metacyclics were produced in all cultures maintained with glutamine in the concentration range 2-20 mM, optimum numbers were obtained between 4 and 12 mM glutamine. This pattern was constant in flasks cultured for over two months. The substitution of glutamine by proline in culture medium did not influence the number of metacyclic forms produced. Removal of proline or glutamine from cultures producing metacyclics caused a rapid fall in production of metacyclic forms which could be reversed by re-introduction of either nutrient. Cultures of another stock of T. congolense responded similarly when maintained in different concentrations of glutamine, showing that the effect may be a general one. PMID- 2892366 TI - Dose and stage dependency for the development of local skin reactions caused by Trypanosoma congolense in goats. AB - Intradermal inoculation of metacyclic forms of Trypanosoma congolense propagated in vitro caused skin reactions in goats similar to the local skin reaction (chancre) induced by the bite of an infected tsetse fly. The onset, size and duration of these local skin reactions were dose-dependent. Whereas one cultured metacyclic T. congolense was sufficient to cause a local skin reaction in a goat, over 10(7) bloodstream forms of T. congolense were necessary to elicit a detectable skin reaction and while T. congolense parasites present in lymph did not cause local skin reactions, trypanosomes collected from oedematous fluid of the chancre did. - Using non-dividing irradiated bloodstream forms it was estimated that 10(8) T. congolense were required to induce a detectable local skin reaction. - Intradermal needle inoculation of procyclic forms (uncoated trypomastigotes) of T. congolense propagated in vitro induced an intense inflammatory response which was similar to that found in the early phases of the reaction elicited by metacyclic trypanosomes. This suggests that the uncoated trypomastigotes which are known to be present in the saliva of infected tsetse may play a role in the initial development of the chancre. - The data obtained for the local skin reaction suggest the presence of an intracutaneous dividing stage of T. congolense which is intermediate between the metacyclic and bloodstream forms. PMID- 2892367 TI - High density lipoprotein levels in the serum of trypanosensitive and trypanoresistant cattle. Changes during Trypanosoma congolense infection. AB - Nonpermissiveness to trypanosome infection has been correlated in some instances with the presence of toxic serum factors, e.g. high density lipoproteins (HDL) of human serum can lyse T.b. brucei. The present study examines the possibility of a role for such factors in West African cattle that are resistant to trypanosomiasis. Cattle used in this study were previously selected as resistant or sensitive to trypanosomiasis under heavy natural Glossina challenge. - A comparison of the direct effect of serum from trypanoresistant and trypanosensitive Baoule cattle on the development of pathogenic bloodstream or metacyclic forms of T. congolense, using modifications of the blood infectivity incubation test, failed to demonstrate a difference between these cattle. High density lipoproteins and cholesterol levels were compared in 115 cattle of known sensibility to trypanosomiasis. HDL-cholesterol formed 91% of the total plasma cholesterol. HDL-cholesterol levels in Zebu (mean of 111.8 mg/100 ml) were significantly higher than those in Baoule cattle (86.2 mg/100 ml). There was no significant difference, however, in these levels between trypanoresistant (73.4 mg/100 ml) and trypanosensitive (84.5 mg/100 ml) Baoule. Alterations in HDL cholesterol levels were monitored during an experimental cyclic infection with T. congolense in 5 Zebu and 9 Baoule. HDL-cholesterol levels decreased in all animals concomitantly with the appearance of trypanosomes in the blood and returned rapidly to their starting values after parasite elimination following drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892368 TI - The effect of Trypanosoma brucei infection of the localization of salivary gland cholinesterase in Glossina morsitans morsitans. AB - When salivary glands of the tsetse fly, Glossina morsitans morsitans, are stained for cholinesterase (ChE) activity, a net-like pattern of reaction product is observed surrounding each epithelial cell of the gland's secretory region. Glands infected with Trypanosoma brucei brucei show a progressive reduction in this ChE activity as the parasites develop. When the infection is mature, ChE is rarely detected in the epithelial layer but appears in the lumen of gland. The luminal ChE responds to substrates and inhibitors in the same manner as the epithelium associated enzyme and appears to have leaked from the epithelium due to cellular damage in epithelium of the infected gland. The possible effect of glandular damage on feeding behaviour and state of health is discussed. PMID- 2892369 TI - [Modification of the behavior of Glossina palpalis palpalis linked to the swine fever epizootic of 1982 in a Congolese village]. AB - A swine fever epizootic decimated the pig herds in villages within the Yamba focus of human trypanosomiasis. Ecological studies of Glossina palpalis palpalis populations were carried out in one of the villages for four years following the disappearance of the pigs, which had been the principal nutritive host of the Glossina in the area. One important behavioural modification occurred, namely the establishment of a small peridomestic tsetse population. The flies deserted the patches of residual forest to settle around the periphery of the village. This probably occurred in numerous other villages where the epizootic had destroyed the herds of pigs. The modified behaviour has increased the man-fly contact, but, on the other hand, facilitates vector control. PMID- 2892370 TI - Immune serum from both susceptible and resistant strains of mice increases phagocytosis of Leishmania mexicana amazonensis by macrophages. AB - Immune sera obtained from either BALB/c mice (susceptible) at 7 weeks, or C57BL/6 mice (resistant), at 7 weeks after infection with L. m. amazonensis, were effective in increasing internalization of homologous promastigotes into starch induced peritoneal macrophages (from both mouse strains). Both the internalization enhancing effect and the levels of anti-leishmanial antibody (ELISA) were removed from sera by absorption with heat-killed promastigotes. Sera at 1/200 dilution obtained from either mouse strain at 2 weeks after infection did not enhance parasite internalization into macrophages. The factors leading to susceptibility or resistance during leishmaniasis do not appear to be related to differences in antibody-mediated opsonic activity. PMID- 2892371 TI - Characterization of immunosuppressive proteins of Brugia malayi microfilariae. AB - Inhibition of Concanavalin A-induced lymphocyte proliferation was used to monitor the partial purification and characterization of suppressor molecules from microfilariae of Brugia malayi. Suppressor activity was present in high molecular weight fractions of microfilarial extracts (Mr greater than 50 kd on SDS-PAGE) and was protease-sensitive but resisted treatment with sodium periodate, indicating that it is associated with parasite proteins. Suppressor activity was released by microfilariae cultured in vitro and could be detected in peritoneal exudates of intraperitoneally-infected jirds and in lymph and sera from athymic C3H/HeN mice with patent B. malayi infections. These findings indicate that immune unresponsiveness during patent filarial infections may result from the in vivo release by microfilariae of high molecular weight proteins that suppress host immune responses. PMID- 2892372 TI - Increase in natural killer cell activity during diethylcarbamazine treatment of patients with filariasis. AB - Two patients, one with Bancroftian filariasis and the other with onchocerciasis, and two healthy controls were treated with diethylcarbamazine (DEC). The natural killer (NK) cell activity of the two patients increased during DEC treatment to 2.5 and 2.8 times, respectively, while that of the controls remained unchanged. We conclude that the augmentation of baseline NK cell activity, as well as interferon- and interleukin-2-enhanced NK cell activity seen in the patients, is not a direct effect of DEC, but is related to the reaction to DEC in lymphatic filariasis and onchocerciasis. PMID- 2892373 TI - Clinical experience with metrifonate. Review with emphasis on its use in endemic areas. AB - Metrifonate is an excellent drug for the treatment of urinary schistosomiasis in areas with S. haematobium monoinfection. Toxicity apparently is negligible. Side effects due to the inhibition of acetylcholinesterase are usually scarce, light and transient in nature. At the recommended dosage of 3 times 10 mg/kg the chemotherapeutic potential of metrifonate to cure can be expected to range between 60 and 90%. Each dose of metrifonate reduces egg excretion by almost 90%. Treatment with metrifonate clearly reverses lower and upper renal tract pathology. An intermittent course of metrifonate may be administered by minimally trained health personnel. When appropriately timed with regards to local transmission dynamics the minimal requirement to achieve 99% reduction of egg excretion may be as low as three or four doses spaced over a period of two years. PMID- 2892374 TI - The effect of the trypanocidal drugs berenil and samorin on infections of Glossina morsitans centralis by Trypanosoma congolense. PMID- 2892375 TI - Studies on experimental infection of pigs with Trypanosoma brucei. PMID- 2892376 TI - Adaptation of Trypanosoma congolense stocks to in vitro culture does not change their sensitivity to isometamidium. PMID- 2892377 TI - The promastigote surface protease of Leishmania donovani infantum in the midgut of Phlebotomus perniciosus. PMID- 2892378 TI - The influence of the isolation technique of influenza virus nucleoprotein on its antigenic properties. AB - ELISA has been used to study the antigenic properties 1. of influenza virus nucleoprotein (NP-1) isolated from virions with the help of preparative polyacrylamide gel electrophoresis (PAGE); 2. of virion ribonucleoprotein (NP-2), and 3. of NP structures prepared by dissociation of ribonucleoprotein into RNA and protein in sucrose gradient containing NaCl (NP-3). The investigation of immunologic cross-reactivity has shown complete identity of NP-2 and NP-3 and their striking difference from NP-1. In contrast to NP-2, NP-3 was not contaminated by other virus antigens, it was a good immunogen and could be used for preparation of monospecific antisera of high titre. NP-1 did not induce a high antibody response,however, like NP-2 and NP-3, it retained its capacity to react with antisera to native virus. Owing to its simple production and high yield, this protein can be used in serodiagnosis for testing the antibody level against NP-protein in convalescent sera. PMID- 2892379 TI - HSV-1 infection and immunity in immunosuppressed mice. AB - The effect of cyclophosphamide (CY) and hydrocortisone (HY) on the susceptibility of mice to intracerebral and intraperitoneal infection with herpes simplex virus type 1 (HSV-1) was investigated. The mean survival time, the survival ration, the localization of HSV-1 antigen in brain, spleen and liver as well as immunity after immunization with inactivated virus were determined. In the case of primary infection, an increased susceptibility to HSV-1 was observed after administration of the immunosuppressive drug. Immunization increased the resistance of mice to virus challenge, but no such effect was observed when the virus challenge, but no such effect was observed when or HY. The influence of CY and HY on the immunization process itself was divergent: when HY was given at the time of immunization, the resistance to virus challenge was abolished. On the other hand, CY given simultaneously with inactivated HSV-1 did not depress the immunization effect. PMID- 2892380 TI - Dynamic model of the pathogenesis of Mengo virus infection in mice. AB - A mathematical model of the pathogenesis of experimental Mengo virus infection in mice has been developed and fitted using kinetic data of both virus multiplication in different organs and mortality. The behaviour of the model proved to be bistable. In contrast to the widely accepted hypothesis that an acutely virus-infected host dies when virus replication has attained a critical level in the main target organ, the present results showed the following: the maximum virus titre in brain, the main target organ, has been reached already 24 hr post infection (p.i.) but the animals began to die since 60 hr. Hence, it was postulated and confirmed by a good model fit to the experimental data that the so called AUC (area under the curve) of the virus multiplication kinetics may be a critical quantity. From this finding a hypothesis was deduced assuming that in the presence of high amounts of the virus the antiviral effect of IFN wanes with time. Since this process accounts for death, it may be a potential target of antiviral therapy. PMID- 2892381 TI - Production in Vero cells of an inactivated rabies vaccine from strain FRV/K for animal and human use. AB - A new concentrated and purified rabies vaccine was produced in Vero cells. Two rabies virus strains, the fixed rabies virus Pasteur (FRV) and Pittman Moore (PM) were adapted to Vero cells by 20 cycles of alternating passages in the brain of weaning mice. Intracerebral (i.c.) inoculation of weaning mice was followed then by 17 and 20 serial passages in Vero cells of RFV and PM strains, respectively. The adapted strains designated as FRV/K and PM/K gave titres of 10(6) +/- 1.5 log (LD50/ml for i.c. inoculated mice) in several harvests taken from one infected cell culture. Pooled harvests were concentrated 20-fold by ultrafiltration and were tested as animal vaccine after inactivation with beta-propiolactone (BPL). Another vaccine preparation destined for human use, in addition to concentration and inactivation, was also purified by gel filtration. Control tests revealed that the antigenic content of different strain FRV/K harvests was very high in comparison with that of strain PM/K and the reference tissue culture vaccine (RIV, Netherland). In sheep the antibody response induced by the FRV/K strain was very high; serum neutralizing index (NI) higher than 4 was reached 40 days after the second vaccine dose, whereas the vaccine preparation from strain PM/K gave NI of 2.3 and the reference vaccine NI of 3.8, respectively. Safety tests in rabbits and guinea pigs showed neither pyrogenicity nor toxicity. PMID- 2892382 TI - Efficacy of (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil against acute herpes simplex virus keratitis and the establishment of latency: comparison with acyclovir and bromovinyldeoxyuridine. AB - Four nucleoside analogues--acyclovir [9-(2-hydroxyethoxymethyl)guanine], bromovinyldeoxyuridine [(E)-5-(2-bromovinyl)-2-deoxyuridine], vinylarauracil 5 vinyl-1-beta-D-arabinofuranosyluracil and bromovinylarauracil [(E)-5-(2 bromovinyl)-1-beta-D-arabinofuranosyluracil]--were compared in the therapy of acute keratitis induced in the rabbit cornea by inoculation of the KUPKA strain of herpes simplex virus type 1 (HSV-1). In comparison to placebo-treated animals, the drugs reduced the mean plaque counts in conjunctival swabs as follows: acyclovir to 0.16-1.73%, bromovinyldeoxyuridine to 0.02-0.25%, vinylarauracil to 0.55-5.96% and bromovinylarauracil to 0.12-3.39% of control values. Latency was established to a most limited extent in 1 or 2 out of 5 rabbits treated with vinylarauracil or bromovinylarauracil, respectively. One or 6 out of 84 or 98 explanted ganglion fragments (1.3 or 6%) were positive for HSV-1 as compared to 72 fragments out of 173 (43%) from placebo-treated rabbits. Acyclovir and bromovinyldeoxyuridine completely prevented latency. PMID- 2892383 TI - Clinical and morphologic studies on the guinea pig eye infected with human influenza virus strains of different virulence. AB - Human influenza virus serotypes H3N2 and H2N2 caused iridocyclitis and uveitis when inoculated at does of 10(6) 6.5 EID50 into the guinea pig eye anterior chamber. Virulent influenza virus strains and their attenuated variants prepared by passaging in chick embryos (CE) have been compared in this model. These studies showed that virulent viruses cause more severe damage in the eyes than the attenuated strains. PMID- 2892384 TI - Pathomorphologic characterization of CNS damage in monkeys infected with persistent variant of measles virus vaccine strain L-16. AB - The lesions of CNS were examined in monkeys infected intracerebrally (i.c.) with a variant of measles virus vaccine strain L-16 isolated after prolonged persistence in human cell culture NEr-2. The persisting virus variant appeared pathogenic for monkeys. The changes which had developed in their CNS within 30 to 60 days post-infection (p.i.) were alike to acute measles encephalitis which was evidenced by giant cell formation at the injection site. Twenty-two months p.i. the chronic character of lesions was evident from the appearance of foci of neuron destruction. Based on morphologic findings it was suggested that strain L 16-H has acquired some properties characteristic of nonattenuated virus. PMID- 2892385 TI - Enzyme secretion by human endothelial cells infected with Rickettsia conorii. AB - When cultured endothelial cells from the human umbilical vein were infected with rickettsia conorii, a greater increase was noticed in the inhibitor of plasminogen activator than in tissue type plasminogen activator. This could be linked to clinical observation of coagulation abnormalities in Boutonneuse fever (BF). Otherwise, transaminase levels increased significantly in the supernatant of R. conorii infected endothelial cells which could explain the increased levels of these enzyme in BF. PMID- 2892386 TI - Specific IgM antibodies in the saliva of mumps patients. AB - Antibodies to mumps virus were detected in 63.5% of saliva samples from mumps patients. The secretory antibody response was of primary type. Specific IgM antibodies were found in some samples collected early after the onset of disease. Specific IgA were detected in later obtained samples. Persons over 15 years of age reacted more often and more promptly than the children. The authors discuss the possible significance of prior antigenic stimulation by related paramyxoviruses (namely parainfluenzaviruses) for the intensity of local antibody response to mumps virus infection. PMID- 2892387 TI - Beta-adrenergic blockers in pregnancy. PMID- 2892388 TI - Impact of smoking on heart attacks, strokes, blood pressure control, drug dose, and quality of life aspects in the International Prospective Primary Prevention Study in Hypertension. AB - Effects of smoking are highlighted in a posthoc analysis of this randomized, double-blind International Prospective Primary Prevention Study in Hypertension (IPPPSH). At the time of entry, 37% of the men and 23% of the women were smoking cigarettes, and only 537 patients changed their smoking status during the trial. In men and women, smoking doubled cardiac and cerebrovascular event rates. Nonsmoking men had fewer myocardial infarctions and sudden deaths when treated with oxprenolol. Smoking status did not affect in-study blood pressure control, the type of drugs, or the combinations used, but smokers were given higher doses of oxprenolol. For a given blood pressure during antihypertensive treatment, rates for cardiac and cerebrovascular events were higher in smokers. Heart rates were higher in both oxprenolol and non-beta-blocker-treated smokers. Smoking dose dependently increased hematocrit level. Among physician-elicited symptoms, dyspnea and cold extremities were more frequent in smokers, whereas dyspnea, headaches, impotence, dizziness, and anxiety states were common, with unsatisfactory blood pressure control (diastolic blood pressure greater than 95 mm Hg). Quality of life may be more jeopardized by smoking, poor blood pressure control, or diuretic use than by beta-blocker-based therapy. In the IPPPSH, the patient who smoked had double the cardiovascular complication rates without cardiac benefit from the beta-blocker despite higher doses given; the higher heart rate and hematocrit level may have been contributing factors. PMID- 2892389 TI - Cardiac symptoms and anxiety disorders: contributing factors and pharmacologic treatment. AB - Anxiety may have deleterious effects on the cardiovascular system in persons who have, or are predisposed to have, cardiovascular disease. Contributing factors consist of the type of anxiety, constitutional characteristics and personality traits. The treatment of anxiety thus has a beneficial effect on patients with cardiovascular disease. However, anxiety reduction through medication, even if it includes subjective improvement in somatic symptoms, should not necessarily be equated with beneficial effects on the cardiovascular system. Three groups of medication used in the treatment of anxiety have different effects. Antidepressants lower psychic anxiety but may have the opposite effect on the cardiovascular system, whereas beta-adrenergic blockers lower sympathetic tone without affecting psychic anxiety. Only benzodiazepines fulfill both functions. Since subjective reports of somatic, including cardiovascular, changes correlate poorly with physiologic changes, assessment of new medications should not rely on self-reported improvement in cardiac symptoms but should include objective measures as well. PMID- 2892391 TI - Treatment of ulcerative colitis with oral 5-aminosalicylic acid including patients with adverse reactions to sulfasalazine. AB - Sulfasalazine is an effective drug for maintaining remission in ulcerative colitis, but its use may be precluded by side effects. Eighty-five patients with active ulcerative colitis participated in a prospective open trial to examine the tolerance of the active constituent 5-aminosalicylic acid (5-ASA), coated with an acrylic resin, and its efficacy in inducing and subsequently maintaining a remission. Fifty-one of the patients had previously developed adverse reactions to sulfasalazine. After 4 wk of treatment with 3.2 g 5-ASA daily, a remission was achieved in 23 of 36 patients (64%) with mild or moderate disease, but in none of 43 patients with severe disease. Six patients were withdrawn because of side effects to 5-ASA, but only two of these patients had similar reactions on sulfasalazine. Supplementary corticosteroids for 6 wk or less induced a remission in 27 of the patients who had failed on 5-ASA alone. Fifty patients were therefore eligible for the maintenance phase of the trial, and 39 (78%) had a sustained clinical and endoscopic remission upon 1-yr follow-up. 5-ASA appears to be an effective drug for inducing remission in mild or moderate ulcerative colitis and for the maintenance of remission. It thus represents a valuable addition to the management of patients intolerant to sulfasalazine. PMID- 2892390 TI - Folate transport in ileal brush border-membrane vesicles following extensive resection of proximal and middle small intestine in the rat. AB - Uptake of folic acid (PteGlu) was examined in remnant ileum of rats after resection of 65% of the small intestine with the brush border-membrane vesicle technique. The results were compared to that of sham-operated rats. In both rat groups transport of PteGlu was linear for approximately 40 s of incubation and was similar in the presence of a Na+ and a K+ gradient (out greater than in). In resected rats transport of PteGlu was inhibited by the structural analogues 5 methyltetrahydrofolate (5-CH3H4PteGlu) and methotrexate (MTX), by sulfasalazine, and by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and was saturable as a function of concentration (apparent Kt = 18.3 microM). In the ileum of sham-operated rats, on the other hand, transport of PteGlu was not affected by 5-CH3H4PteGlu, MTX, sulfasalazine, or DIDS and was linear with concentration. These results suggest that the PteGlu transport system is induced in remnant ileum of the rat after extensive intestinal resection. PMID- 2892392 TI - Effect of nizatidine and cimetidine on betazole-stimulated gastric secretion of normal subjects: comparison of effects on acid, water, and pepsin. AB - The effect of nizatidine, a new histamine H2 receptor antagonist, on gastric secretory function of eight normal subjects stimulated with betazole, was compared with that of cimetidine. Single oral doses of 75 mg, 150 mg, and 300 mg nizatidine, 300 mg cimetidine, and a placebo were administered on separate occasions 1 h before betazole stimulation. Gastric secretions were recovered in 15-min fractions for the ensuing 2 h, and the pH, H+ concentration and output, volume, and pepsin concentration and output were determined. Doses of 150 mg and 300 mg nizatidine depressed the secretory response significantly more than did cimetidine. The antisecretory effects of 75 mg nizatidine was no different than that of 300 mg cimetidine. Nizatidine 300 mg inhibited pepsin output significantly more than volume. Although pepsin concentration was reduced more than volume, the difference was not significant. These observations, in contrast to results of previous studies, suggest a direct inhibition of pepsin secretion, although to a lesser extent than that of acid. PMID- 2892393 TI - Polyarteritis nodosa involving only the main renal arteries. AB - A unique case of accelerated hypertension and acute anuria in a 24-year-old man is presented. Clinically, the patient was found to have obstruction of both main renal arteries caused by extensive bilateral thrombosis. Microscopically, a healing panarteritis involving only the main renal arteries was found. This was associated with acute renal infarction and tubular atrophy in the left kidney. This appears to be an unusual variant of polyarteritis nodosa limited to both main renal arteries. PMID- 2892395 TI - A polymorphic DNA marker that represents a conserved expressed sequence in the region of the Huntington disease gene. AB - A polymorphic marker (D4S62) that is genetically closely linked to D4S10 and is in the region of the gene for Huntington disease is described. A four-allele polymorphism is detected when HincII-digested DNA is hybridized with D4S62. D4S62 maps, by Southern blot analysis using somatic-cell hybrids, to 4p16.1 closer to the centromere than does D4S10. The use of the polymorphisms detected by D4S62 increases the informativeness of markers close to the gene for Huntington disease and will be useful for preclinical diagnosis. D4S62 detects transcripts of approximately 6,000 nucleotides in rat, mouse, and monkey liver and brain. This represents the first demonstration of conserved expressed sequences close to the gene for Huntington disease. PMID- 2892394 TI - The detection of linkage disequilibrium between closely linked markers: RFLPs at the AI-CIII apolipoprotein genes. AB - Study of very closely linked DNA variants at various loci has frequently shown linkage disequilibrium. We studied three closely linked RFLPs at the apolipoprotein AI-CIII locus. Two variants detected by MspI and SstI were in strong linkage disequilibrium; but when conventional statistical tests were used, a third variant (PstI), located between the MspI and SstI markers, appeared to be in linkage equilibrium with these two "outside" markers. Similar discrepancies from the expected monotone relationship between physical distance and linkage disequilibrium have been reported by others. To investigate these discrepancies, the power to detect linkage disequilibrium was calculated. It could be shown that, for the gene frequencies encountered, very large sample sizes would be required to demonstrate negative (i.e., repulsion-phase) linkage disequilibrium. Such numbers are usually very difficult to attain in human studies. Failure to demonstrate linkage disequilibrium by conventional methods therefore does not imply its absence. Appropriate nomograms and tables are provided. PMID- 2892398 TI - Alternative bioassays of kinship between loci. AB - In this study four asymptotically equivalent estimates of kinship are derived, in the general case and for kinship between multiallelic loci. Two estimates based on chi 2 agree closely, with the Shannon estimate giving the smaller variance. The PAH, GH, GM, and HBB systems conform to a recombinational model with an evolutionary size of approximately 4,000 and a ratio of recombination to physical distance of approximately 1.4 X 10(-5) morgans/kb, as predicted on the basis of the genetic and physical lengths of the human genome. The INS and D11S12 systems have a much more rapid decline of kinship with physical distance, suggesting overlapping RFLPs (unrecognized allelism), recombinational hot spots, or selection. Sources of error in predicting kinship over small distances are discussed. PMID- 2892397 TI - Insulin-gene sharing in sib pairs with insulin-dependent diabetes mellitus: no evidence for linkage. AB - An association between insulin-dependent diabetes mellitus (IDDM) and an RFLP adjacent to the insulin gene has been consistently observed, but its etiological significance is unclear. We studied unrelated IDDM patients (N = 45) and controls (N = 65) to confirm the association--and assessed evidence for linkage in 22 families with at least two affected (IDDM) sibs--to determine whether the insulin gene region actually contributes to susceptibility to IDDM. All individuals were typed for the RFLP in the 5'-flanking region of the insulin gene (5'FP) used in the previous studies, and the 12 families not fully informative for linkage with the 5'FP were typed for additional closely linked RFLPs. We found a higher frequency of class 1 alleles of the 5'FP in IDDM patients (.83) than in controls (.75), which is consistent with the reported association, but the difference was not statistically significant in our sample. Among the 33 affected sib pairs (ASPs) in 22 families, if maximum possible sharing is assumed when sharing is ambiguous, 10 pairs share both parental insulin genes, 17 pairs share one, and six share neither. This distribution is incompatible with close linkage. In contrast, for the HLA region, for which all 22 families are fully informative, 19 of the 33 ASPs share two haplotypes and the remaining 14 share one. There are no pairs that share neither HLA haplotype. Thus, although these data clearly illustrate the contribution of HLA-linked susceptibility to IDDM, they argue strongly against a contribution of similar magnitude by the insulin-gene region. PMID- 2892396 TI - Identification of more than 500 RFLPs by screening random genomic clones. AB - As part of our genome-mapping effort, we undertook a large-scale screening study to identify RFLPs useful as genetic markers. Some 1,664 single-copy or repeat containing phage clones from a Charon 4A genomic library were tested for polymorphism against a panel of DNAs, from five unrelated individuals, digested with eight restriction enzymes. Approximately 30% (515) of the clones revealed polymorphism by Southern hybridization; 67 loci detected had PIC values greater than .5. Restriction enzymes MspI, TaqI, and RsaI were most efficient in detecting polymorphism within the 1-20-kb-fragment size range resolved. With only one exception each of the clones detected polymorphism originating from a single locus. PMID- 2892399 TI - The relative efficiency of restriction enzymes: an update. PMID- 2892400 TI - Refined linkage map of chromosome 7 in the region of the cystic fibrosis gene. AB - The genetic map in the region of human chromosome 7 that harbors the gene for cystic fibrosis (CF) has been refined by multilocus linkage studies in an expanded database including a large set of normal families. Six loci known to be linked to CF were examined: MET, an oncogene; COL1A2, collagen, TCRB, T-cell receptor beta polypeptide; and three arbitrary loci--D7S8, D7S13, and D7S16- defined by probes pJ3.11, pB79a, and p7C22, respectively. The gene order with greatest statistical support is COL1A2-D7S13-D7S16-MET-D7S8-TCRB. Linkage analysis in families segregating for CF suggested that the most likely location of the CF gene on this map is between MET and D7S8. PMID- 2892403 TI - Evolving perspectives on parenteral H2-receptor antagonist therapy. PMID- 2892402 TI - Linkage studies in a new X-linked myopathy, suggesting exclusion of DMD locus and tentative assignment to distal Xq. AB - We here report linkage studies in a family suffering from a recently described hereditary muscle disease named X-linked myopathy with excessive autophagy (XMEA). Significant lod scores excluding linkage to the Duchenne-Becker muscular dystrophy locus were found. Several other loci on the short and long arms of the X chromosome produced negative lod scores, whereas probe DX13-7 defining locus DXS15 showed no recombinants and a lod score of z = 0.903 at theta = .0. Further studies should be done to determine whether the gene for XMEA is (1) located at Xq and (2) caused by a mutation of the Emery-Dreifuss muscular dystrophy gene, which has been assigned to the same region. PMID- 2892401 TI - Detection of a NotI polymorphism with the pmetH probe by pulsed-field gel electrophoresis. AB - The pmetH probe, tightly linked to the locus for cystic fibrosis (CF), detected a NotI polymorphism with allele sizes of 1,000 and 550 kb that could be separated by pulsed-field gel electrophoresis. Both alleles were found on chromosomes bearing either the normal or the CF allele. Preliminary data showed that this polymorphism was not in strong linkage disequilibrium with the CF locus. Preliminary large-scale restriction mapping of the fragment showed that the NotI polymorphic site is 200-370 kb distant from the MET locus; thus it defines a new polymorphic locus in the CF region. This locus is of potential interest for studying CF families that show recombinants between CF and its tightly linked probes, in order to increase the precision of the genetic map of the region. PMID- 2892404 TI - Evolving perspectives on parenteral H2-receptor antagonist therapy. Symposium. Tucson, Arizona, April l0-11, 1987. PMID- 2892405 TI - Pharmacodynamics and pharmacokinetics of parenteral histamine (H2)-receptor antagonists. AB - Parenteral histamine (H2)-receptor antagonists are frequently used to prevent upper gastrointestinal bleeding caused by stress-induced gastric mucosal damage in critically ill patients. It is generally agreed that the goal of therapy in this syndrome is the consistent elevation of gastric pH levels above a certain value, often set at 4, in order to prevent the underlying mucosal damage from progressing to bleeding. The three H2-receptor antagonists currently available in a parenteral form and suitable for this mode of prophylaxis are cimetidine, ranitidine, and famotidine. The pharmacodynamic and pharmacokinetic properties of these agents, as they relate to their use in prevention of stress ulceration bleeding, are discussed here. These agents are more noted for their pharmacodynamic and pharmacokinetic similarities in acid suppression, elimination, and metabolism than for their differences. Ranitidine and famotidine are more potent than cimetidine, and famotidine has a slightly longer half-life than do cimetidine and ranitidine, but current dosing recommendations take these differences into account so that the agents have equivalent efficacy. Cimetidine and ranitidine have been widely used in this application. Less experience has been obtained, to date, with famotidine. Recent studies with primed, continuous infusions of cimetidine indicate that dosing schedule may be the key to obtaining better efficacy in prophylaxis of stress-related mucosal damage. Similar studies with ranitidine have not yielded results as promising as those with cimetidine, however, and few data are available on famotidine. PMID- 2892406 TI - Comparative efficacy of parenteral histamine (H2)-antagonists in acid suppression for the prevention of stress ulceration. AB - Stress-related mucosal damage is related to a high intraluminal hydrogen ion concentration, a low intramural pH value, and a breakdown of the gastric mucosal barrier. Because the presence of gastric acid is required for stress-related mucosal damage to occur, therapy aimed at increasing intraluminal pH values has often been used as prophylaxis against complications. The amount of acid suppression required for adequate prophylaxis of gastrointestinal bleeding from stress-related mucosal damage has not been determined, but many investigators use a target gastric pH level of 3.5 to 4.0. When intravenous histamine (H2)-receptor antagonists are given in bolus dosing regimens to critically ill patients, fluctuations in gastric pH values are often observed, as might be expected. However, recent studies with primed continuous infusion of cimetidine in critically ill patients have demonstrated that consistent elevation of gastric pH to 4.0 may be attained with this regimen. Studies with continuous infusions of ranitidine are less conclusive; little information is available on famotidine. PMID- 2892407 TI - Prophylaxis for pulmonary acid aspiration. AB - Pulmonary acid aspiration in the perioperative period was first noted as a medical concern more than 40 years ago. Despite this awareness, identification of the patient at risk is by no means certain, and the true incidence of this condition is not known. Various therapeutic interventions have been proposed and tried. Physical therapies, such as pressure on the cricoid, have been successful, as has the administration of clear antacids prior to surgery. The histamine (H2) receptor antagonists cimetidine and ranitidine have also been used successfully as prophylactic therapy when enough time is available prior to operation to make preoperative dosing practical. Metoclopramide, which can be given intravenously, may be useful in emergency surgery. When the degree of risk is high, concurrent use of physical and pharmaceutical interventions is recommended. PMID- 2892408 TI - Role of histamine (H2)-receptor antagonists in total parenteral nutrition patients. AB - Hospitalized patients, especially those who are critically ill, are often at risk for malnutrition and may require nutritional support. Although the enteral approach is generally preferred when providing nutritional support, parenteral nutrition is frequently required. These patients are also likely to receive therapeutic or prophylactic parenteral histamine (H2)-receptor antagonists. Patients receiving both total parenteral nutrition and parenteral H2-receptor antagonists may benefit from receiving the drug in combination with the total parenteral nutrition admixture. Parenteral cimetidine and ranitidine are stable in various total parenteral nutrition fluids. Clinically, cimetidine has been studied more extensively than ranitidine. Clinical benefits and cost savings may be realized from this method of drug delivery. PMID- 2892409 TI - Safety perspectives on parenteral H2-receptor antagonists. AB - Much controversy has been associated with the similarities and differences among the histamine (H2)-receptor antagonists with respect to safety. The safety issues, including those recently identified with the use of parenteral H2 receptor antagonists, are analyzed here with the intent of placing these data into proper perspective. The focus of the analysis is on a few of the more important issues: central nervous system effects and clinically significant drug interactions. A review of the voluminous safety literature on these agents indicates that, as a class, they have enviable safety records. When individual agents are compared, some small differences in safety profiles emerge, but, on the whole, similarities are more striking. PMID- 2892410 TI - Hepatotoxic and hepatoprotective potential of histamine (H2)-receptor antagonists. AB - It has been increasingly recognized that the histamine (H2)-receptor antagonists are associated in rare instances with idiosyncratic hepatotoxic reactions and with drug interactions related to their inhibition of the hepatic cytochrome P 450 enzymes. What have not been appreciated until recently are the potential therapeutic benefits that may be derived from cytochrome P-450 inhibition. Evidence is presented here that cytochrome P-450 inhibition may protect against hepatic damage induced by acetaminophen and other drugs metabolized via this system. Acetaminophen hepatotoxicity is an especially important problem because of the widespread use of this agent and the evidence that the potential for such injury may be increased in alcoholic persons. Cimetidine has been used in selected cases, one of which is described here, to treat acetaminophen hepatotoxicity. All H2-receptor antagonists may not be alike in this regard. Experimental studies in animal models indicate that although cimetidine protects against the hepatotoxic effects of acetaminophen, ranitidine may actually potentiate hepatic damage. It is thought that the difference between these two H2 receptor antagonists may lie in their affinities for binding to the cytochrome P 450 enzymes. Cimetidine, which binds more strongly, inhibits this system more efficiently, whereas the inhibition produced by ranitidine is not sufficient to confer a protective effect against drug-induced hepatotoxicity. PMID- 2892411 TI - Considerations for selection of parenteral histamine (H2)-receptor antagonists. AB - Parenteral histamine (H2)-receptor antagonists are safe and effective therapy for the prophylaxis of stress-related erosive syndrome. Of the three agents available, parenteral cimetidine is the most widely studied; parenteral formulations of ranitidine and famotidine have not been investigated as extensively. Parenteral cimetidine appears to be effective in reducing incidence and complications associated with gastrointestinal hemorrhage caused by stress related erosive syndrome, although its effects on bleeding that has already begun are not clear. Antacids are also effective in decreasing the incidence of stress related gastrointestinal hemorrhage, but they are inconvenient and expensive to administer. Primed continuous of stress-related erosive syndrome in critically ill patients; the evidence available on the efficacy of continuous infusions of ranitidine is inconsistent, and very few data are available on the value of famotidine. Direct comparative clinical trials are needed to assess definitively the efficacy of primed continuous infusions of cimetidine or other H2-receptor antagonists versus that of antacid therapy. PMID- 2892412 TI - Restriction fragment length polymorphisms of the insulin gene hypervariable region in gestational onset diabetes mellitus. AB - Restriction fragment length polymorphisms in the insulin gene hypervariable region are compared among 93 women with gestational onset diabetes mellitus and 146 women with normal glucose tolerance during pregnancy. No significant differences in gene or genotype frequencies were observed in the overall sample (p greater than 0.50). However, an increased frequency of one allele (class 1) was observed among nonoverweight patients with gestational onset diabetes mellitus with elevated fasting plasma glucose levels compared with age-, race-, and parity-matched control subjects (p = 0.061). These data suggest that gestational onset diabetes mellitus is a heterogeneous disorder with respect to both genotypic and phenotypic characteristics, and that restriction fragment length polymorphisms near the insulin gene may serve as a molecular marker for susceptibility to gestational onset diabetes mellitus only in some women. PMID- 2892414 TI - Modified protocols improve insulin sensitivity estimation using the minimal model. AB - We attempted to improve the precision of the estimation of insulin sensitivity (S1) from the minimal model technique by modifying insulin dynamics during a frequently sampled intravenous glucose tolerance test (FSIGT). Tolbutamide and somatostatin (SRIF) were used to change the insulin dynamics without directly affecting insulin sensitivity. Injection of tolbutamide (100 mg) at t = 20 min provoked an immediate secondary peak in insulin response, resulting in a greater integrated incremental insulin than the standard FSIGT. SRIF, injected at t = -1 min, delayed insulin secretion in proportion to the dose without any change in magnitude. Computer simulation was used to assess the precision of S1 estimation. Insulin dynamics from both standard and modified protocols were adjusted in magnitude, with the shape unchanged and analyzed to determine the effect of the magnitude of insulin response. Fractional standard deviation was reduced from 73% with the standard insulin profile to 23% with tolbutamide and 18% with the highest dose of SRIF. In addition, the fractional standard deviation of S1 estimates decreased exponentially with increasing magnitude of insulin response. Modified FSIGTs require a smaller insulin response than the standard protocol to achieve the same precision. PMID- 2892415 TI - Neural regulation of gastrin and somatostatin secretion in rat gastric antral mucosa. AB - A muscle-stripped mucosal sheet obtained from rat antrum was mounted in an Ussing chamber and used to examine the regulation of gastrin and somatostatin secretion by antral neurons. The neurons were activated pharmacologically with 1,1-dimethyl 4-phenylpiperazinium (DMPP) or electrically by field stimulation using aluminum foil electrodes layered over the edge of the mucosal sheet. Field stimulation caused an increase in gastrin and somatostatin secretion that was dependent on the strength of the stimulus (10-30 V). Field stimulation at 30 V, 10 Hz, 4 ms caused a sixfold increase in gastrin and a twofold increase in somatostatin secretion that were nearly abolished by tetrodotoxin (85-89% inhibition). Atropine partially inhibited the gastrin response (34 +/- 6%) but had no effect on the somatostatin response. DMPP caused lesser, though significant, increases in gastrin (166%) and somatostatin (83%) secretion that were nearly abolished by hexamethonium (84-91%) but were not significantly affected by atropine. The increase in somatostatin secretion caused by DMPP and field stimulation, as well as the resistance of gastrin and somatostatin secretion to atropine, was consistent with preferential activation of noncholinergic neurons at the stimulatory modalities used. The pattern and magnitude of gastrin and somatostatin response to pharmacological and electrical stimulation of antral neurons were similar to those previously observed in the vascularly perfused whole rat stomach. PMID- 2892413 TI - Effects of inhibition of mitochondrial protein synthesis in skeletal muscle. AB - To evaluate the participation of proteins derived from mitochondrial genes in the adaptive response of skeletal muscle to increased contractile activity, we administered chloramphenicol (CAP; 200-1,000 mg.kg-1.day-1), an inhibitor of translation from mitochondrial ribosomes, to adult rabbits undergoing electrical stimulation of the tibialis anterior muscle of one hind limb. In unmedicated animals, 10 days of electrical stimulation increased maximum velocity (Vmax) of cytochrome oxidase and citrate synthase by 214 +/- 17 and 201 +/- 16% (P less than 0.01). In a dose-dependent manner, CAP abolished activity-induced increases in cytochrome oxidase Vmax, suggesting that augmented mitochondrial protein synthesis is necessary for the adaptive response of enzymes that require protein subunits encoded by mitochondrial genes. However, CAP failed to inhibit activity induced changes in Vmax of enzymes derived exclusively from nuclear genes (citrate synthase and aldolase). CAP also failed to inhibit activity-induced increases in mRNA transcribed from the nuclear genes encoding beta-F1 ATPase or myoglobin, or from the mitochondrial genes encoding 12S rRNA, 16S rRNA, or cytochrome b. These latter findings suggest that mitochondrial translation products do not participate in pretranslational regulation of these nuclear or mitochondrial genes in response to changes in contractile activity of skeletal muscle. PMID- 2892416 TI - GRP-producing nerves control antral somatostatin and gastrin secretion in pigs. AB - By immunohistochemistry, nerve fibers containing gastrin-releasing polypeptide (GRP)-like immunoreactivity were identified close to the somatostatin (SS) producing cells of the gastric antral mucosa. We, therefore, studied the possible role of GRP in the control of antral SS secretion by use of isolated perfused pig antrum with intact vagus nerve supply. Electrical stimulation of the vagus nerves at 4 Hz increased the antral release of GRP up to 10-fold and increased SS output 2- to 3-fold. Atropine at 10(-6) M had no effect on these responses. Intra arterial GRP increased SS secretion significantly at 10(-10) M and eightfold at 10(-8) M, whereas gastrin secretion was stimulated significantly at 10(-11) M and maximally at 10(-10) M and inhibited at 10(-8) M. Preperfusion with a GRP antagonist ([D-Arg1,D-Pro2,D-Trp7,9,Leu11]substance P) or Fab fragments of antibodies against GRP abolished the effects of vagus stimulation on gastrin and somatostatin output. Gastrin in concentrations up to 10(-7) M was without effect on SS secretion. We conclude that electrical stimulation of the vagus nerves increases antral SS gastrin secretion and that GRP is a likely transmitter. PMID- 2892417 TI - T84 cell receptor binding and guanyl cyclase activation by Escherichia coli heat stable toxin. AB - Escherichia coli heat-stable enterotoxin (STa) induces intestinal secretion by binding to enterocyte receptors and activating the guanylate cyclase-guanosine 3',5'-cyclic monophosphate (cGMP) system. The intermediate steps between binding of STa and secretion are poorly understood, due in part to the lack of a convenient system to study the effects of STa at the cellular level. To establish such a model, we investigated the binding of 125I-STa, STa activation of guanylate cyclase, and STa-induced increase in cGMP production in a well characterized human colonic cell line, T84. Binding was specific, linear with cell number, and time, temperature and pH dependent, and reversible. ST may also be internalized by these cells. Addition of unlabeled STa competitively inhibited binding of 125I-STa. These parameters closely resemble those described in intact rat enterocytes and cell-free membrane preparations. STa stimulated guanylate cyclase and cGMP production in a dose-related manner. The similar dose-response relationships for binding, guanylate cyclase stimulation by STa, and cGMP production suggest that the guanylate cyclase-cGMP system is coupled to ST occupancy of specific receptors. These data, together with the fact that STa induces chloride secretion from T84 cells suggest that T84 cells are a suitable and convenient system to study the cellular mechanism of action of STa. PMID- 2892418 TI - Characterization of amino acid metabolism by cultured rat kidney cells: study with 15N. AB - The present study evaluates the metabolism of glutamine and glutamate by normal rat kidney (NRK) cells. The major aim was to evaluate the effect of acute acidosis on the metabolism of amino acid and ammonia formation by cultured NRK cells. Experiments at either pH 7.0 or 7.4 were conducted with phosphate-buffered saline supplemented with either 1 mM [5-15N]glutamine, [2-15N]glutamine, or [15N]glutamate. Incubation with either glutamine or glutamate as a precursor showed that production of ammonia and glucose was increased significantly at pH 7.0 vs. 7.4. The disappearance [corrected] of glutamine and glutamate was linear during a 60-min incubation at either pH. In experiments with [5-15N]glutamine, we found that approximately 57 and 43% of ammonia N was derived from 5-N of glutamine at pH 7.4 and 7.0, respectively. Experiments with [2-15N]glutamine or [15N]glutamate indicated that approximately 43 and 47% of 2-N glutamine and glutamate N utilization, respectively, was accounted for by ammonia production at pH 7.0. Similarly, 28 and 29% of NH3 was derived from 2-N of glutamine or glutamate N by activity of glutamate dehydrogenase at pH 7.4. In addition to 15NH3 formation, three major metabolic pathways of [2-15N]glutamine or [15N]glutamate disposal were identified: 1) transamination reactions involving the pH-independent formation of [15N] aspartate and [15N]alanine; 2) the synthesis of [6-15NH2]adenine nucleotide, a process more active at pH 7.4 vs. 7.0; and 3) glutamine synthesis from [15N]glutamate, especially at pH 7.4. The data indicate that NRK cells in culture consume glutamine and glutamate and generate ammonia and various amino acids, depending on the H+ concentration in the media. The studies suggest that these cell lines may provide a useful model for studying various aspects of the effect of pH on rat renal ammoniagenesis. PMID- 2892419 TI - Prostacyclin reduces "preload" in conscious dogs via a vagal reflex mechanism. AB - The purpose of this study was to determine the effects of prostacyclin on left ventricular (LV) preload in conscious dogs. LV end-diastolic diameter (LV EDD) was used as an index of preload. Because prostacyclin reduces arterial pressure, data were sampled when mean arterial pressure, heart rate, and first derivative of LV pressure (dP/dt) had returned to control levels. There was no dose-response relationship in the preload reduction to prostacyclin, the threshold dose being 0.1 microgram/kg. Intravenous prostacyclin (2.0 micrograms/kg) reduced LV EDD 2.9 +/- 0.5% from 36 +/- 2.2 mm, (P less than 0.01). With heart rate held constant (146 +/- 2.5 beats/min) by electrical pacing, prostacyclin still reduced LV EDD by 4.0 +/- 1.0% from 32 +/- 2.5 mm (P less than 0.05). Intravenous administration of arachidonic acid (500 micrograms/kg) gave similar results. The magnitude of the preload response to prostacyclin was similar to that of nitroglycerin (25 micrograms/kg). Prazosin (1 mg/kg) or bilateral cervical vagal section completely abolished the preload response to prostacyclin but not to nitroglycerin. We, therefore, propose a mechanism where prostacyclin activates cardiopulmonary receptors with vagal afferents that results in a withdrawal of peripheral sympathetic tone to capacitance vessels to reduce preload, in contrast to nitroglycerin, whose mechanism of action is most probably a direct effect on capacitance vessels. PMID- 2892420 TI - Renal vascular reactivity to U 46619 and adrenergic agonists in Goldblatt hypertension. AB - Vascular reactivity of the contralateral kidney of conscious Goldblatt hypertensive dogs was studied by eliciting renal blood flow (RBF) responses to intra-arterial infusions of vasoconstrictor and vasodilator agonists in control sessions and at weekly intervals postclipping. Systemic arterial blood pressure (BP) and RBF were monitored during each recording session via an implanted catheter and electromagnetic blood flow probe, respectively. BP was maximally increased within 1 wk and remained elevated for the duration of the study. The relationship between the negative percent change in RBF (-% delta RBF) and the renal arterial plasma concentration of adrenergic agonists, angiotensin II and thromboxane mimetic (U 46619), infused intra-arterially was subjected to regression analysis, and 25 and 50% effective doses (ED25 and ED50, respectively) were calculated. Vascular sensitivity to phenylephrine and norepinephrine increased within a month or more of hypertension. Vascular reactivity to angiotensin II was unchanged. In contrast to the delayed increase in renal vascular reactivity to adrenergic agonists, enhancement of the RBF responses to U 46619 was seen within 1-2 wk. In addition, beta-adrenoceptor-mediated vasodilation appeared suppressed during hypertension. Alteration in the response of the contralateral kidney to both vasoconstrictor and beta-adrenoceptor mediated vasodilator stimuli may contribute to renal hemodynamic changes in Goldblatt hypertension. PMID- 2892421 TI - Age-related changes in adrenergic vasoconstrictor responses of the rat hindlimb. AB - Vascular adrenergic responses were examined in the hindlimb perfused with blood at constant flow using pentobarbital-anesthetized male Fischer 344 rats aged 6, 12, 20, and 24 mo. The increase in hindlimb perfusion pressure to lumbar sympathetic nerve stimulation was significantly smaller in 20- and 24-mo-old rats than in younger animals, whereas vasoconstrictor responses to intraarterial administration of norepinephrine, L-phenylephrine, and methoxamine were reduced only in the 24-mo-old animals. Thus neurogenic vasoconstriction in the hindlimb is reduced at 20 mo of age, whereas there is a more generalized postjunctional loss of adrenergic responsiveness at 24 mo. In the presence of the beta adrenoceptor antagonist, propranolol, vasoconstrictor responses to exogenous norepinephrine did not differ when 12- and 20-mo-old animals were compared. Furthermore, in the presence of propranolol the nerve-mediated rise in hindlimb perfusion pressure also did not differ in 12- and 20-mo-old rats. Blockade of neuronal norepinephrine uptake with cocaine produced a greater potentiation of vasoconstrictor responses to both nerve stimulation and exogenous norepinephrine in the older rats. Therefore, the reduced nerve-mediated vasoconstriction in 20 mo-old rats may be due to neuronal activation of beta-adrenoceptors as well as enhanced neuronal norepinephrine reuptake. PMID- 2892423 TI - Biliary catabolism of glutathione and differential reabsorption of its amino acid constituents. AB - Biliary excretion of glutathione, free amino acids, and total amino acids (after acid hydrolysis) was measured in hepatic bile collected from guinea pigs, rabbits, and dogs anesthetized with pentobarbital sodium. In controls, the concentration of glutathione in bile was less than 20 microM in all three species. However, when hepatic gamma-glutamyltransferase activity was decreased by retrograde intrabiliary infusion of the irreversible inhibitor acivicin (AT 125; 20 mumol/kg), there was a marked increase in biliary glutathione excretion (in mumol glutathione equivalents.kg body wt-1.h-1) from 0.10 +/- 0.04 to 2.2 +/- 0.6 in guinea pigs, from 0.014 +/- 0.013 to 2.5 +/- 1.9 in rabbits, and from an undetectable level (less than 0.001) to 0.11 +/- 0.05 in dogs. Amino acid analysis of bile revealed that the concentration of glutathione's constituent amino acids (free glutamate, cystine, and glycine) in control bile samples from these three species were quite low and were not affected by AT-125. However, acid hydrolyzates of these same bile samples revealed an unusually high degree of amino acid conjugation. Glutamate (0.06-0.5 mM), cystine (0.2-1.1 mM), and glycine (1.7-2.8 mM) constituted the overwhelming majority of total amino acids in hydrolyzed bile from controls. After AT-125, concentrations of total glutamate and cystine were elevated in hydrolyzed bile, while concentrations of all other amino acids remained the same. Thus glutathione is avidly secreted into bile in the guinea pig, rabbit, and dog but is almost quantitatively broken down within the biliary tree. Subsequently, the glutamate and cysteine moieties derived from catabolism of glutathione must be partially reabsorbed either as peptides, conjugates, or free amino acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892422 TI - Beta-adrenergic stimulation of brown adipocyte proliferation. AB - The mechanisms of brown adipose tissue (BAT) growth were studied by quantitative photonic radioautography using tritiated thymidine to follow mitotic activity. To identify the nature of the adrenergic pathways mediating brown adipocyte proliferation and differentiation, the effects of cold exposure (4 days at 4 degrees C) on BAT growth were compared with those induced by treating rats at 25 degrees C with norepinephrine (a mixed agonist), isoproterenol (a beta-agonist), and phenylephrine (an alpha-agonist). The drugs were continuously administrated via osmotic minipumps (0.375 mumol/h during 4 days) implanted subcutaneously. Cold exposure markedly enhanced the mitotic activity in brown adipocyte precursor cells (interstitial cells and preadipocytes) and endothelial cells forming the numerous capillaries. Norepinephrine mimicked the effects of cold exposure, not only on the mitotic activity, but also on the distribution of the labeling among the various cellular types. Isoproterenol entirely reproduced the effects of norepinephrine both on the labeling index and on the cellular type labeling frequency. In contrast, phenylephrine did not stimulate cell division. These results demonstrate that norepinephrine triggers a coordinated proliferation of brown adipocytes and endothelial cells in warm-exposed rats that is similar to that observed after cold exposure. They also suggest that cold exposure stimulates BAT growth by increasing the release of norepinephrine from sympathetic nerves and that the neurohormone activates mitoses in BAT precursor cells via beta-adrenergic pathways. PMID- 2892424 TI - Identical patterns of somatostatin secretion from isolated antrum and fundus of rat stomach. AB - The patterns of somatostatin secretion from the fundus, the main source of somatostatin, and the antrum, the site of paracrine regulation of gastrin secretion, were examined using perifused antral and fundic segments from rat stomach. Gastrin secretion fundic segments from rat stomach. Gastrin secretion could be obtained from antral segments only. Somatostatin secretion was obtained from both antral and fundic segments. 1,1-Dimethyl-4-phenylpiperazinium (DMPP) (10(-5) and 10(-4) M) and bombesin-14 (10(-8) and 10(-6) M) caused concentration dependent increases in somatostatin secretion that were of the same magnitude in antral and fundic segments. These increases were also of the same magnitude as those obtained in the vascularly perfused whole stomach. Atropine (3 X 10(-7) M) inhibited the somatostatin response to DMPP (10(-4) M) to the same extent in antral (50 +/- 12% inhibition) and fundic (55 +/- 12% inhibition) segments. Hexamethonium (10(-5) M) also inhibited the response to DMPP to the same extent in antral (80 +/- 9%) and fundic (78 +/- 19%) segments. Methacholine caused a typically muscarinic decrease in somatostatin secretion that was of the same magnitude in antral (27 +/- 6%) and fundic (25 +/- 6%) segments. The identical patterns of somatostatin secretion from the two regions of the stomach imply that somatostatin secretion measured in the vascularly perfused whole stomach is a valid reflection of somatostatin secretion by the antrum. PMID- 2892425 TI - Renal ammoniagenic response to chronic acid loading: role of glucocorticoids. AB - Adrenalectomized (ADX) animals exhibit a blunted renal response to chronic acid loading. To determine whether this response truly reflects impaired renal ammoniagenesis from glutamine, urinary ammonium excretion was compared with acid intake in ADX, intact, and ADX rats supplemented with either a low dose (4 micrograms.100 g-1.day-1) or a high dose (40 micrograms.100 g-1.day-1) of triamcinolone. ADX rats consumed similar amounts of acid as did intact controls yet excreted only 37% of the load as ammonium; in contrast intact controls returned 86% and triamcinolone-supplemented animals returned 98 and 88% for low and high doses, respectively. Nor could the reduced ammonium excretion be attributed to increased renal venous release, since total ammonia production, the sum of renal venous and urine ammonium, was reduced to 49% of the intact controls; low- and high-dose triamcinolone restored and markedly increased the production rate. Underlying the impaired ammonia production rate in ADX rats was a reduced rate of glutamine extraction, 350 +/- 49 vs. 896 +/- 102 and 1,260 +/- 247 and 1,448 +/- 112 nmol.min-1.100 g-1 for intact and low and high doses, respectively. Unlike intact acidotic and glucocorticoid-supplemented ADX acidotic rats, glutamine extraction was disassociated from the delivered glutamine load consonant with the role of glucocorticoid in coupling cellular glutamine transport to its metabolic utilization. PMID- 2892426 TI - Proton-translocating ATPase from bovine kidney medulla: partial purification and reconstitution. AB - The proton-translocating ATPase that is responsible both for urinary and vacuolar acidification was partially purified from bovine kidney medulla microsomes. ATPase activity was purified to a maximum specific activity of 1.7 mumol.min-1.mg prot-1 and was inhibited completely by N-ethylmaleimide. The relative molecular weight (Mr) of the intact protein estimated by high-pressure size-exclusion liquid chromatography was 586,000. Nondenaturing gels of the isolated enzyme revealed two protein bands at MrS of 551,000 and 523,000. Sodium dodecyl sulfate gel electrophoresis of the isolated H+-ATPase revealed component subunits at MrS of 70,000, 56,000, 45,000, 42,000, 38,000, 31,000, 15,000, 14,000, and 12,000. The properties of the isolated H+-ATPase and of microsomal ATP-dependent proton transport correlated closely. The isolated H+-ATPase was reconstituted into phospholipid liposomes and demonstrated N-ethylmaleimide-inhibitable ATP dependent potential generation, consistent with electrogenic proton transport. In overall structure, the enzyme appears to be a new type of H+-ATPase with several features of the F0F1 class of ion-translocating ATPases but is immunologically and structurally different from the mitochondrial F1-ATPase. PMID- 2892428 TI - The role of external heat load in triggering the neuroleptic malignant syndrome. AB - During a heat wave three patients developed neuroleptic malignant syndrome. The role of heat load in triggering this syndrome and possible mechanisms behind such a role are discussed. Data concerning the season of occurrence of neuroleptic malignant syndrome are reported. PMID- 2892427 TI - Angiotensin II facilitation of pressor responses to adrenal field stimulation in pithed rats. AB - The effects of angiotensin II on pressor responses to electrical field stimulation (1-32 Hz) of the adrenal gland were assessed in pithed male Sprague Dawley rats. Stimulation elicited frequency-related pressor responses and increments in plasma catecholamines. Interruption of the renin-angiotensin system with the converting enzyme inhibitor captopril or the receptor antagonist saralasin significantly attenuated the pressor responses to adrenal stimulation and injected epinephrine to an equivalent extent. This observation, along with the finding that captopril did not alter the plasma catecholamine increments produced by adrenal stimulation, suggested that endogenously generated angiotensin II was not affecting adrenal catecholamine release. Instead angiotensin II appears to interact at the level of the vascular smooth muscle, because reinfusion of angiotensin II (20 ng.kg-1.min-1 iv) in captopril-treated animals restored responsiveness to stimulation and epinephrine. Infusion of vasopressin also restored pressor activity after captopril; therefore the interaction does not appear to be specific for angiotensin II but may depend on the background tone of the vascular smooth muscle. Moreover, decreasing blood pressure with sodium nitroprusside reversibly attenuated the pressor responses to both adrenal stimulation and epinephrine. The results suggest that endogenously formed angiotensin II facilitates the vasoconstrictor activity of epinephrine by increasing vascular tone. PMID- 2892429 TI - Immunohistologic study of the leukocytic infiltrate in maternal uterine tissues in normal and preeclamptic pregnancies at term. AB - The leukocytic infiltrate in maternal uterine tissues at term in normal and preeclamptic pregnancies was studied immunohistologically using a number of monoclonal antibodies. No differences in the quantity and type of infiltrate are apparent between normal and preeclamptic pregnancy tissues. A large population of macrophages has been identified. Suppressor/cytotoxic T lymphocytes expressing major histocompatibility complex (MHC) class II products but lacking interleukin 2 receptor expression constitute the other component of the bone marrow-derived cell population. The suppressor/cytotoxic cells are seen around both arteries with and without physiologic changes and are seen also in acute atherosis. While it is suggested that the maternal immune response, further functional studies of these leukocytes are required to define their role in normal pregnancy. PMID- 2892431 TI - Vecuronium and bradycardia. PMID- 2892432 TI - Bradycardia, vecuronium and atracurium. PMID- 2892430 TI - [Hemodynamics under propofol-nitrous oxide anesthesia: effects of premedication with lormetazepam and of additional fentanyl]. AB - Propofol, in both its new oil-in-water emulsion and the former cremophor-EL solution, is known to produce significant decreases in arterial blood pressure. The aim of this study was to obtain a precise hemodynamic profile of anesthesia induction with propofol under conditions of daily routine (additional 70% nitrous oxide) and to evaluate the influence of (1) premedication with lormetazepam and (2) additional i.v. injection of fentanyl. Forty patients (ASA classes I and II) were randomly assigned to one of four groups (A, B, C, and D). Anesthesia was induced with a sleep dose of propofol (mean: 2.4 mg/kg) and the patient was ventilated with 30% O2 and 70% N2O via a face mask. In groups B and D, 3 micrograms/kg fentanyl were injected immediately prior to propofol injection. Patients in groups A and B received no premedication. Patients in groups C and D received 2 mg lormetazepam on the evening prior to the anesthetic and 1 mg 2 h prior to the anesthetic orally. The following parameters were determined immediately prior to induction of anesthesia and 1, 3, 5, 8, and 10 min after the start of the propofol injection: heart rate (HR), mean arterial blood pressure (MAP), mean pulmonary artery pressure (PAP), central venous pressure (CVP), pulmonary occlusion pressure (POP), cardiac output (CO), stroke volume (SV), and systemic vascular resistance (SVR). In all four groups a slight decrease in HR and SVR occurred while a marked decrease in arterial blood pressure (SAP, MAP, DAP) and cardiac output was seen. PAP and preload pressures showed no significant changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892433 TI - Laparoscopy in adults and children with nonpalpable testes. AB - Laparoscopy was performed in 31 patients presenting 36 nonpalpable testes. Sixteen adults had a chronological age of 15 to 33 years (average 21 years) and fifteen children had a chronological age of 2 to 13 years (average 6 years). Among 20 investigated testes in 16 adults, 11 (55%) were sighted in the abdominal cavity. Vessels and deferens were seen entering the inner inguinal ring in 5 cases (25%). Vascular and gonadal structures were not found in four cases (20%). Among 16 investigated testes in 15 children, 10 (62,5%) were sighted in the abdominal cavity. Vessels and deferens entering the inner inguinal ring were sighted in 2 cases (12,5%). Nothing was found in two cases (12,5%). Blind ending vas sighted in 1 case (6,25%) and one exam was not conclusive because of intestinal adherence in 1 case (6,25%). The laparoscopy proved to be an accurate diagnosis method in 34 (94,5%) of 36 cases of nonpalpable examined testes. PMID- 2892434 TI - Anatomy of the testis and epididymis in cryptorchidism. AB - The types and incidence of deformities in the proximal seminal pathways have been carefully studied in 150 consecutive orchidopexies. 85% of the testicles were found in the subcutaneous tissue, 15% were in the canal or the abdomen. Malunion between the testis and the epididymis was the type of anomaly most frequently encountered. Deformities considered to affect fertility were seen in 70% of the gonads located proximal to the external inguinal ring and in 12% of the subcutaneous testicles. The difference is statistically significant. PMID- 2892435 TI - Intra- and inter-observer variability in the assessment of testicular descent. AB - Measurements of the distance between the testis and the pubic tubercle have been used to differentiate retractile testes from "real" cryptorchidism and to measure the effect of therapy. The intra- and inter-observer variation of these measurements was determined in 21 boys with incompletely descended testes treated with placebo. Patients were investigated in supine and squatting position, before and during moderate caudal traction. In squatting position the average distance is 20 mm greater than in supine position. The intra-observer SD is approximately 10 mm. It is doubtful if quantitative measurements can be used to define retractile testes. The wide prediction intervals should be taken into account in interpreting results of therapy. PMID- 2892436 TI - Age-dependence of the dose-response curve of vecuronium in pediatric patients during balanced anesthesia. AB - The effect of age on the log-based cumulative dose-response curve of vecuronium was determined in ten age groups of 80 pediatric patients ranging from neonates to adolescents during thiopental-fentanyl-N2O/O2 anesthesia. Neuromuscular block was recorded as the evoked thenar electromyographic response to train-of-four stimulation of the ulnar nerve (2 Hz at 20-second intervals). The dose-response curves were parallel to each other in all ten age groups studied. In neonates and infants, the ED95 of vecuronium was 47 +/- 11 (SD) micrograms/kg. This was significantly lower than the ED95 of 81 +/- 12 micrograms/kg in children between 3 and 10 years of age (P less than 0.01). In patients aged 13 years or older, the ED95 was 55 +/- 12 micrograms/kg, which did not differ from the neonatal and infant values but was significantly lower than the ED95 of children between 3 and 10 years of age. The results indicate that the dose of vecuronium necessary for tracheal intubation is age-dependent. The individual ED95 values varied between 22 and 103 micrograms/kg. This suggests that an individually optimal dose of vecuronium can be administered to pediatric patients only if neuromuscular block is adequately monitored. PMID- 2892437 TI - Rapid administration of a narcotic and neuromuscular blocker: a hemodynamic comparison of fentanyl, sufentanil, pancuronium, and vecuronium. AB - High-dose narcotic anesthetic inductions usually avoid circulatory depression better than do other techniques; however, the selection of a narcotic and neuromuscular blocker influences subsequent hemodynamic responses. One hundred one patients having aortocoronary bypass graft (CABG) surgery were investigated using four combinations of a narcotic and neuromuscular blocker: group FP (fentanyl 50 micrograms/kg, pancuronium 100 micrograms/kg); group FV (fentanyl 50 micrograms/kg, vecuronium 80 micrograms/kg); group SP (sufentanil 10 micrograms/kg, pancuronium 100 micrograms/kg); and group SV (sufentanil 10 micrograms/kg, vecuronium 80 micrograms/kg), each combination being administered over 2 minutes. Hemodynamic functions were then monitored for 10 minutes before tracheal intubation. Significant changes included increases in heart rate in the groups receiving pancuronium and decreases in those receiving vecuronium. In all groups mean arterial pressure initially decreased; systemic vascular resistance index decreased significantly in all groups except SV. Cardiac index decreased significantly only in group SV. Circulatory depression requiring treatment with vasopressor or anticholinergic drugs was more common in patients given vecuronium. Cardiac arrhythmia occurred most often in group SP; only in group FP were there no arrhythmias, ischemic changes, or hemodynamic disturbances requiring intervention. Time to onset of neuromuscular blockade did not differ among the four groups, but transient chest wall rigidity occurred significantly more often with sufentanil than with fentanyl. Overall, the fentanyl/pancuronium combination afforded the greatest hemodynamic stability, whereas the sufentanil/vecuronium combination proved least satisfactory because of bradycardia and hypotension, requiring treatment in 35% of group SV patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892438 TI - Changes in sufentanil pharmacokinetics within the neonatal period. PMID- 2892440 TI - Sinus node exit block following administration of vecuronium. PMID- 2892439 TI - Sufentanil analgesia following cesarean section: epidural versus intravenous administration. PMID- 2892442 TI - Histamine and the preclinical pharmacology of cetirizine. PMID- 2892441 TI - Effects of beta- and alpha-adrenergic agonists, adenosine, and carbachol in heart muscle isolated from malignant hyperthermia susceptible swine. AB - During malignant hyperthermia crisis, cardiac arrhythmias and increased myocardial oxygen consumption are observed. It was the purpose of the present study to investigate whether or not a greater sensitivity to cardiac alpha- or beta-adrenoceptor stimulation or an impaired adenosine- or m-cholinoceptor mediated inhibition of beta-adrenergic stimulation contributes to the cardiac symptoms of malignant hyperthermia. The effects of phenylephrine, isoproterenol, adenosine, [-]-N6-phenylisopropyladenosine (PIA), and carbachol on force of contraction were studied in electrically driven trabeculae isolated from the left ventricles of malignant hyperthermia susceptible (MHS) and healthy control pigs. The positive inotropic effects of phenylephrine and of isoproterenol were similar in MHS and control pigs. The EC50 values for the inotropic effect of phenylephrine were 4.1 (2.1-8.3) mumol.l-1 (n = 9) in MHS and 6.3 (3.4-12.9) mumol.l-1 (n = 9) in control swine. The maximal positive inotropic effects at 30 mumol.l-1 phenylephrine also did not differ in both groups (176.7 +/- 14.4% of pre-phenylephrine value in MHS swine, n = 9; 170.3 +/- 15.9% of pre-phenylephrine value in control swine, n = 9). The EC50 values for isoproterenol were 0.16 (0.06 0.39) mumol.l-1 (n = 9) and 0.19 (0.05-0.29) mumol.l-1 (n = 9) in MHS and control swine, respectively. The maximal positive inotropic effects at 1 mumol.l-1 isoproterenol were also similar (213.8 +/- 12.6% of the pre-isoproterenol value in MHS swine, n = 9; 216.4 +/- 36.0% of the pre-isoproterenol value in control swine, n = 9). Also, no difference could be detected in the antiadrenergic effects of adenosine, PIA, or carbachol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892443 TI - Cetirizine, a recent advance in selective antihistamine therapy. Proceedings of a symposium. May 29-30, 1987, Naples, Florida. PMID- 2892444 TI - In vitro effects of cetirizine and histamine on human neutrophil function. AB - IgE-mediated hypersensitivity reactions are characterized by an immediate or early-phase response within the first 30 minutes of exposure to allergen, followed by a late-phase response that begins two to six hours later. Histamine is released during both the early- and late-phase responses and inhibits a variety of neutrophil functions, including superoxide anion generation, chemotaxis, and enzyme secretion. There is some debate as to whether histamine's action on neutrophils is mediated through H1 or H2 receptors, or through a single receptor that recognizes both H1 and H2 agonists. In an effort to understand the mechanism of action of the H1-antagonist cetirizine, we studied its effects on a variety of neutrophil functions. We found that at concentrations up to 35 micrograms/mL), it does not affect superoxide anion production or degranulation. However, at higher concentrations (greater than 35 micrograms/mL), a concentration-dependent inhibition of superoxide anion production is observed. This inhibition is most apparent with responses stimulated by chemotactic factors. Limited inhibition of degranulation and chemotaxis is also seen at high concentrations, but at a level far below that seen with superoxide anion production. These studies indicate that neutrophil function is not altered by the circulating concentrations of cetirizine attained during therapy (less than 10 micrograms/mL), but may be suppressed at higher concentrations. Additional effects of cetirizine on neutrophil function, possible influences of the drug on the inflammatory response, and histamine's modulation of neutrophil function are discussed. PMID- 2892445 TI - The comparative pharmacokinetics of H1-receptor antagonists. AB - H1-receptor antagonists appear to be absorbed rapidly after oral administration, with peak serum concentrations being reached one to three hours after a dose. For most of these drugs, the absolute bioavailability is unknown because no intravenous formulations are available for comparative purposes. The serum elimination half-life values of these agents are variable: a few hours for terfenadine and triprolidine; about 9 hours for cetirizine, azatadine, and loratadine; from 20 to 25 hours for hydroxyzine, chlorpheniramine, and brompheniramine; and from 5 to 14 days for astemizole. Few pharmacokinetic studies of H1-receptor antagonists in children have been reported. However, it is known that chlorpheniramine, hydroxyzine, cetirizine, and terfenadine have shorter elimination half-life values in children than in adults. Regardless of the age of patients, for most of the H1-receptor antagonists the apparent volumes of distribution and total body clearances appear to be large (3.4 to 18.5 L/kg and 4.4 to 32.1 mL/min/kg, respectively). Cetirizine is an exception, with values of 0.8 L/kg and 0.5 mL/min/kg. Urinary excretion of unchanged antihistamine is higher after cetirizine (60% of dose) than any other H1 blocker. For H1-receptor antagonists with long half-life values, steady state may not be reached for several days (chlorpheniramine and brompheniramine) or several weeks (astemizole), and significant accumulation of drug occurs if the dosing interval is more frequent than every half-life. There is no evidence for the introduction of metabolism of H1-receptor antagonists, even after months of treatment. PMID- 2892446 TI - Pharmacokinetics of cetirizine in the elderly and patients with renal insufficiency. AB - The disposition of cetirizine, a new H1-receptor antagonist, was evaluated in 30 healthy adults of various ages and in 15 adults with various degrees of renal insufficiency. The purpose of the evaluation was to determine whether dosage schedules of cetirizine will require modification in the elderly or patients with renal insufficiency. We found that the elimination half-life of cetirizine was prolonged in patients with mild and moderate renal insufficiency, compared with age-matched individuals with normal renal function (19.0 +/- 3.3 and 20.9 +/- 4.4 hours, vs 7.4 +/- 3.0 hours, respectively). However, the mean apparent steady state volume of distribution did not differ significantly between these subject groups (range 0.41 to 0.47 L/kg). Total body clearance and renal clearance of the drug were both significantly lower in the patients with renal insufficiency. In elderly subjects, the elimination half-life of cetirizine was significantly prolonged compared with younger adults, and apparent total body clearance was significantly reduced. Again, there was no significant difference in the volume of distribution between the groups. Linear regression showed good correlations between the disposition characteristics of cetirizine and age as well as creatinine clearance. However, we found no relationship between age and the ratio of apparent total body clearance of cetirizine to creatinine clearance. Thus the disposition of cetirizine is independent of age but dependent on renal function. The relationship between apparent total body clearance of cetirizine and creatinine clearance was significant only in patients with creatinine clearances greater than 40 mL/min. Progressive decrements in creatinine clearance were not associated with similar changes in the pharmacokinetic parameters of cetirizine. PMID- 2892447 TI - The metabolism and pharmacokinetics of 14C-cetirizine in humans. AB - This study investigated the metabolism and pharmacokinetics of cetirizine, a new H1-receptor antagonist. Single oral doses of 14C-cetirizine dihydrochloride (10 mg) in aqueous solution were administered to six healthy male volunteers. The drug was rapidly absorbed: The peak mean concentration of radioactivity (359 ng equivalents/mL) and of unchanged drug (341 ng/mL) were achieved within one hour. Mean concentrations of cetirizine declined biexponentially and had a mean elimination half-life of 7.4 hours. The drug was excreted quite rapidly, with 60% of the dose recovered in the 24-hour urine. An additional 10% was excreted in urine over the next four days. Approximately 10% of the dose was excreted in feces over the five-day study period. The dose was excreted mainly as the unchanged drug. Examination of the radioactive compounds present in the plasma, and excreted in the urine and feces indicate that there is little metabolism of cetirizine. One minor metabolite, formed by oxidative O-dealkylation of the cetirizine side chain, was detected in plasma and feces. PMID- 2892448 TI - Receptor effects of cetirizine. AB - First-generation H1-antagonist antihistamines such as hydroxyzine have a significant ability to cross the blood-brain barrier and cause sedation, which limits their usefulness in the treatment of allergic disorders. Cetirizine, a carboxylated metabolite of hydroxyzine, possesses the parent compound's antihistaminic activity but does not cause sedation. This lack of CNS effects may be due to cetirizine's greater selectivity or potency at H1 receptors in the brain, compared with its effects at the receptors involved in sedation, or it may result from the agent's relative exclusion from the CNS compartment. We compared cetirizine's activity at central H1 sites with the activity of hydroxyzine and terfenadine. We also compared the abilities of cetirizine and three other antihistamines to cross the blood-brain barrier. We found the drugs' potency at H1 receptors in the CNS to be similar to their activities in other tissues. However, their selectivity varied widely. Cetirizine, in fact, failed to bind at any of the receptors investigated except H1 sites, even at concentrations as high as 10 micron. Both hydroxyzine and D-chlorpheniramine crossed the blood-brain barrier in significant amounts. Terfenadine did so to a much lesser extent, and cetirizine passed into the CNS only half as readily as terfenadine. We suggest that cetirizine's reduced incidence of sedative side effects may stem partly from its selectivity for H1 receptors over sites involved in sedation, and partly from its relative exclusion from the CNS. PMID- 2892449 TI - Clinical pharmacodynamics of antihistamines. AB - Antihistamines act by competing with histamine for H1 or H2 histamine receptors on cell membranes. In addition, most of the common antihistamines bind other receptors and thus exert other pharmacologic actions. For all practical purposes, mast cells and basophils are the main physiologic sources of histamine, and the primary usefulness of antihistamines is in diseases characterized by excessive production and release of histamine by these two cell types. Experimental models have proven useful for evaluating antihistamine compounds in humans. In these model systems, a test drug may be employed to block one or more of the known effects of exogenously administered histamine or a histamine agonist. Or the release of endogenous histamine may be brought about in a controlled fashion by agents such as allergens, opiates, or compound 48/80, and the drug's effects on this process may then be measured. In the case of the central nervous system, unfortunately, such models are not available and other means of evaluation must be devised. The dose response and duration of action of orally administered antihistamines can be determined in a simple skin model by their blocking of the wheal and erythema (flare) resulting from an intradermal challenge with histamine, an allergen, or compound 48/80. Antihistamines can also be evaluated in urticaria induced by scratching or cold. Itching that commonly follows injection of histamine or an allergen into the skin is also inhibited by this class of drugs. Most of the commonly used antihistamines are effective in these models, which form the basis for evaluating antihistamines in the treatment of skin diseases. In the nose and conjunctiva, other model strategies are used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892450 TI - Cetirizine inhibition of histamine-induced bronchospasm. AB - Cetirizine is a potent, selective H1 antagonist recently made available for investigation. To evaluate this oral drug's efficacy in treating asthma, we examined the bronchodilator effects of 5-, 10-, and 20-mg doses as well as the protective effects of these doses against histamine-provoked bronchospasm. Cetirizine's efficacy was compared with that of a placebo and oral hydroxyzine (25 mg) in 10 patients with mild asthma. The new compound provided significant protection in a dose-dependent manner against histamine-induced bronchospasm. A 25-mg oral dose of hydroxyzine, which is partially metabolized to cetirizine, yielded blood levels of cetirizine comparable to those attained with 5 mg of oral cetirizine. Hydroxyzine 25 mg conferred greater protection against histamine bronchoprovocation than placebo, but it gave less protection than 10- and 20-mg doses of cetirizine. Cetirizine in all doses, as well as hydroxyzine at 25 mg, produced significant bronchodilation. However, the bronchodilator effect of the 25-mg hydroxyzine dose was less than that of cetirizine at 20 mg. In this short term study, no significant side effects of cetirizine were noted. PMID- 2892451 TI - Antihistamines, drowsiness, and psychomotor impairment: central nervous system effect of cetirizine. AB - Altered central nervous system function as indicated by drowsiness and impaired psychomotor performance is often a consequence of the use of traditional antihistamines. Demonstration that newer agents lack these CNS effects requires quantitative and objective measurements that are sensitive enough to assess the psychomotor capabilities required for such activities as driving an automobile. These capabilities include extended attention span, vigilance, visual tracking, rapid information processing, and reaction time. We have used several psychomotor function tests to conduct two investigations assessing the CNS effects of cetirizine. In the first study, 12 healthy, atopic subjects received single oral doses of hydroxyzine 25 mg, cetirizine 10 mg and 20 mg, and placebo in a double blind, four-way crossover study. Skin-wheal response to intradermal histamine, psychomotor effects, and serum concentrations of each drug were measured for 36 hours after each dose. The CNS effects were measured using critical flash-fusion frequency tests and Stroop word testing. Perceived feelings of drowsiness were measured using a visual analogue scale (VAS). In the second study, 15 healthy subjects received single oral doses of diphenhydramine 50 mg, cetirizine 5 mg, 10 mg, and 20 mg, and placebo in a double-blind, five-way crossover study. Skin wheal response to intradermal histamine, psychomotor effects, and serum concentrations of each drug were measured for 24 hours after each dose. The CNS effects were measured using digit-symbol substitution testing. "Trails-B" maze tracking, and an analyzer of driving performance that assessed reaction time and vigilance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892452 TI - Cetirizine effects on objective measures of daytime sleepiness and performance. AB - Sixty healthy men and women with no sleep complaints, 21 to 45 years of age (mean age 28), were randomly assigned to one of five parallel groups that received one of the following: cetirizine 5 mg (n = 13), 10 mg (n = 13), or 20 mg (n = 11); hydroxyzine 25 mg (n = 12); or placebo (n = 11). After one adaptation night in the lab, the subjects' sleep patterns were recorded from 2300 to 0730 hours. Subjects were in bed during this period. When they awoke at 0730, a test agent was administered according to double-blind technique. Multiple Sleep Latency Tests (MSLT: 20-minute opportunities to fall asleep in bed while EEG and eye movements are recorded) were given at two-hour intervals throughout the day, and a 30-minute vigilance performance test was given at 1000 and 1600 hours. Subjects receiving cetirizine in doses of 5 to 20 mg did not differ from placebo controls in any objective or subjective measure of daytime alertness. Subjects receiving hydroxyzine were significantly more sedated and showed slower reaction times than the placebo control group for at least four hours after treatment. Self-rated feelings of sleepiness, impairment, and fatigue did not differ significantly between groups. This suggests that hydroxyzine subjects may not have been aware of their sleepiness and slower reaction times. PMID- 2892453 TI - A primate model for the evaluation of antihistamines. AB - Studies of the efficacy of antihistamines in treating human upper airway pathology are difficult to design and conduct. In part, this is the result of a lack of objective measures of the nasal response. The purpose of this study was to develop a monkey model for the objective evaluation of antihistamine effectiveness and, using this model, to study the efficacy of cetirizine. Computer-assisted active anterior rhinomanometry was used to assess nasal airway resistance (NAR) before and after a nasal histamine provocation in conscious rhesus monkeys (Macaca mulatta). To establish dose-response relationships for oral antihistamines in monkeys, we measured the suppression of wheal-and-flare reactions by two such agents, oral cetirizine (CET) 0.1 to 1 mg/kg and chlorpheniramine (CHL) 0.07 to 0.2 mg/kg. The decreases in wheal sizes were maximal 60 to 120 minutes after CET 1.0 mg/kg (90%), and after CHL 0.2 mg/kg (70%). The four monkeys were challenged intranasally with increasing histamine doses (0.5, 1, 5, and 10 mg). The NAR was measured 15 minutes after each dose. At least three days later and 90 minutes after oral pretreatment with either CET 1 mg/kg or CHL 0.2 mg/kg, the intranasal challenges were repeated. Postchallenge NAR data are given as the percent increase from the baseline NAR values. The four monkeys studied had coefficients of variation of 13%, 15%, 16%, and 26% respectively for baseline studies. Mean percent increases in NAR +/- standard deviation were 14% +/- 0.4%, 47% +/- 10.0%, 45% +/- 3.0%, and 72% +/- 6.0% after intranasal challenge with 0.5, 1, 5, and 10 mg of histamine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892454 TI - [Identification of a metabolite of floctafenine in urinary calculi]. AB - There are three 4-amino-quinolines used for their analgesic properties: glafenine, antrafenine and floctafenin. Urinary calculi due to glafenine have been described since 1980. Recently two cases of renal calculi containing antrafenic acid have been reported. We discovered a metabolite of floctafenin in a bladder calculus and describe its identification by infrared spectrophotometry and thin-layer chromatography. PMID- 2892455 TI - [Diagnostic use of the GRF test in the study of GH secretion]. AB - A good response after an intravenous bolus of GRF-1-29 NH2 in patients with hypopituitary dwarfism localities the site of the GH-deficiency in the hypothalamus (GRF deficiency). These patients could be treated with GH and GRF. Never the less some patients with hypothalamic responses after TRH don't respond after GRF. Probably these non responders need GRF in pulsatile or prolonged administration and T4 substitution before and during the test if TSH is also deficient. At least some cases without GRF response can be accepted as pure pituitary only GH would be effective. PMID- 2892456 TI - [Treatment of Raynaud's phenomenon]. PMID- 2892457 TI - Long term follow-up of patients with side to side choledochoduodenostomy and transduodenal sphincteroplasty. AB - From a consecutive series of 190 patients with choledochoduodenostomy (CDD) and 56 patients with transduodenal sphincteroplasty (TDS), there were 10 and 3 hospital deaths respectively. A long term follow-up study was performed on the remainder. Late deaths occurred in 35 CDD and 5 TDS patients. Serious long term complications occurred in 3.3% of CDD cases, comprising 5 cases of 'sump syndrome' and a further case of cholangitis in the presence of a clear biliary tree. Cholangitis occurred in 2 of the TDS patients (3.8%). Recurrent common duct stones were found in 3 of the 'sump syndrome' cases (1.6%) and one of the TDS patients with cholangitis (1.9%). Eighty-eight per cent of the CDD patients and 90.2% of the TDS patients, who were reviewed, were subjectively well. Serum alkaline phosphatase was raised in 21.6% of the CDD patients and only 3.4% of the TDS group (P less than 0.05). Radiological studies showed that the CDD stoma admitted air and barium more often than the TDS stoma (P less than 0.001). Neither the biochemical nor the radiological findings correlated with the long term symptomatic results of the two procedures. Dynamic HIDA scans showed a shorter time to peak activity in the common hepatic duct for both CDD (P less than 0.01) and TDS (P less than 0.05) as compared with endoscopic sphincterotomy (ES). These long-term clinical, biochemical and radiological results are similar to those reported following ES. PMID- 2892458 TI - [Comparative pharmacoclinical study of 2 beta-blockers: atenolol and betaxolol in slight-to-moderate arterial hypertension]. AB - Sixteen patients with mild to moderate hypertension were randomized to receive either atenolol 100 mg a day (group A: 2 females, 6 males, mean age 42.3 years) or betaxolol 20 mg a day (group B: 8 males, mean age 49.3 years), both drugs given once daily for one month with a wash out on the 5th day. Pretreatment blood pressure was significantly higher in group B than in group A: this disparity, linked with randomization, hampered the comparison of the antihypertensive efficacy of both drugs but not the comparison of their pharmacodynamics. The maximal effect on resting supine blood pressure occurred later with betaxolol (4th day) than with atenolol (1st day), while the effect on peak exercise-blood pressure and heart rate was rapidly maximal (1st day) for both beta-blockers. The duration of the antihypertensive action at rest seemed to be nearly similar, while the effects of betaxolol on exercising heart rate and blood pressure were more prolonged than those of atenolol: on the wash out day, plasma atenolol and betaxolol levels fell in a same way but the increase in peak systolic blood pressure was more marked in group A than in group B, so that the positive correlation we found between the plasma drug levels and the percentage of peak systolic blood pressure reduction, was much closer with atenolol (p less than 0.001) than with betaxolol (p less than 0.05). PMID- 2892459 TI - [New forms of 5-aminosalicylate in inflammatory intestinal lesions]. AB - 5 aminosalicylate (5 ASA) represents the active fraction of Salazopyrin. Various preparations, 5 ASA-based, are currently already marketed in the world. Some are reserved for the treatment of distal sites of inflammatory bowel diseases, in the form of enemas and suppositories. The others are used orally by preserving the Salazopyrin structure and its azoic link, like di-ASA (Dipentum) or by coating 5 ASA to allow its release in the distal bowel (Asacol, Claversal, Salofalk, Pentasa). In haemorrhagic recto-colitis, these various preparations have, in the whole, a similar effectiveness to that of Salazopyrin in controlling moderately active forms or in keeping the patient in remission. In Crohn's disease, proof of their activity has not yet been established. The major advantage of these new derivatives rests in their use on patients who do not tolerate or are allergic to Salazopyrin since they are quite well tolerated except for the occurrence of diarrhea. PMID- 2892460 TI - [Polymorphism of p49 Y-specific probe in Papuas Baruyas of Papua New Guinea]. AB - Taq I polymorphism revealed after molecular hybridization with the Y-specific p49 probe was studied in male Papuas, Baruya tribe, living in the Wonenara valley. All individuals screened were identical at the variable loci A, C, F and I, and fixed for the specific allele Db. The deduced haplotype, number 17 (A2, C0, Db, F1, I1) is Baruya-specific. PMID- 2892461 TI - Comparison of the metabolism of linoleic and linolenic acids in the fetal rat. AB - The metabolism by the fetal rat of [1-14C] linoleic acid (18:2 n-6) was compared with that of [1-14C] alpha-linolenic acid (18:3 n-3) studied in vivo and in vitro. Both linoleic and alpha-linolenic acid were rapidly converted to long chain derivatives in fetal brain but rates of delta 6 desaturation were higher for alpha-linolenic than for linoleic acid. In the liver alpha-linolenic, but not linoleic acid, was rapidly converted to long-chain derivatives in vivo. Measurements of delta 6 and delta 5 desaturation by fetal liver in vitro showed significant desaturase activity but this was lower than in the brain. It is suggested that the observed difference in the hepatic metabolism of linoleic compared with that of alpha-linolenic acid reflects their differing affinities for alternative metabolic pathways. PMID- 2892462 TI - Biochemical and cultural analysis of mycobacterial recombinants obtained by spheroplast fusion. AB - Spheroplast fusion using polyethylene glycol 6000 resulted in mycobacterial recombinants with a frequency of about 10(-3). The parental strains were two carotenoid pigment mutants of Mycobacterium aurum which were obtained by chemical mutagenesis of the wild-type strain with N-methyl-N'-nitro-N-nitrosoguanidine. Isolation of recombinant clones was based on their pigmentation on Lowenstein Jensen medium, and genetically stable recombinants were analysed for their carotenoid pigments and their alpha- and beta-mycolic acids. They were then submitted to 14 biochemical tests as well as determination of their susceptibility to 13 drugs and their ability to grow at 30 and 42 degrees C. Recombinants were found to be positive for nitrate reductase (100%), gamma glutamyl transferase (94%), urease (53%) and arylsulphatase (21%). Out of 34 recombinants tested, 5 grew both at 30 degrees and 42 degrees C, whereas 1 grew only at 37 degrees C. The results of drug susceptibility testing were inconclusive. PMID- 2892463 TI - Abnormal glutamate metabolism in amyotrophic lateral sclerosis. AB - Glutamate levels were determined in the fasting plasma of 22 patients with early stage primary amyotrophic lateral sclerosis (ALS) and compared to those of healthy and diseased controls. There was a significant increase (by approximately 100%, p less than 0.0005) in the plasma glutamate of the ALS patients as compared with the controls. Oral glutamate loading (60 mg of monosodium glutamate per kilogram of body weight, taken orally after overnight fasting) resulted in significantly greater elevations in the plasma glutamate and aspartate levels in the ALS patients than in the controls. Glutamate, a potentially neuroexcitotoxic compound, is thought to be the transmitter of the corticospinal tracts and certain spinal cord interneurons. A systemic defect in the metabolism of this amino acid may underlie primary ALS. PMID- 2892464 TI - Familial cases of HTLV-I-associated myelopathy. AB - We studied two familial cases of human T-lymphotropic virus type I (HTLV-I) associated myelopathy from the Kii Peninsula, an area of endemic adult T-cell leukemia-lymphoma (ATLL) in Japan. Incidence of familial clustering of HTLV-I associated myelopathy was about 20%. Type C retrovirus was isolated from cultured cerebrospinal fluid and peripheral blood lymphocytes in both cases. Modes of transmission seem to be similar to those described in ATLL, although there are no reports of both HTLV-I-associated myelopathy and ATLL occurring in the same family. We suggest three possibilities: (1) that the virus associated with HTLV-I associated myelopathy is different from the virus causing ATLL, although they seem to be morphologically and immunologically similar; (2) that HTLV-I associated myelopathy may be determined by the ATLL-causing virus plus a specific genetic background; and (3) some combination of factors 1 and 2. PMID- 2892465 TI - Enhanced degradation of oxidized glutamine synthetase in vitro and after microinjection into hepatoma cells. AB - Mixed-function oxidation of Escherichia coli glutamine synthetase has previously been suggested to mark the enzyme for intracellular degradation, and in vitro studies have demonstrated that oxidation renders the enzyme susceptible to proteolytic attack. In this study, the susceptibility of glutamine synthetase to degradation by purified proteases has been compared with the rate of degradation after microinjection into hepatoma cells. Upon exposure to an ascorbate mixed function oxidation system the enzyme rapidly loses most of its activity, but further oxidation is required to cause susceptibility to extensive proteolytic attack either by a high-molecular-weight liver cysteine proteinase or by trypsin. The rate of degradation of biosynthetically 14C-labeled native and oxidized glutamine synthetase preparations after injection into hepatoma cells parallels their susceptibility to proteolysis in vitro. Native enzyme preparations and enzyme oxidatively inactivated, but not susceptible to extensive degradation by purified proteases, had similar intracellular half-lives; however, oxidized enzyme preparations that were susceptible to proteolytic breakdown in vitro were degraded almost ten times faster than the native enzyme within the growing hepatoma cells. These results suggest that the same features of the oxidized enzyme that render it susceptible to proteolysis in vitro are also recognized by the intracellular degradation system. In addition, they show that loss of enzyme activity does not necessarily imply decreased metabolic stability. PMID- 2892466 TI - The halobacterial H+-translocating ATP synthase relates to the eukaryotic anion sensitive H+-ATPase. AB - The H+-translocating ATP synthase of Halobacterium halobium (Y. Mukohata and M. Yoshida (1987) J. Biochem. 102, 797-802) includes a catalytic moiety of 320 kDa which is isolated as an azide-insensitive ATPase (T. Nanba and Y. Mukohata (1987) J. Biochem. 102, 591-598). The polyclonal antibody against this archaebacterial ATPase cross-reacts with the anion-sensitive H+-ATPase of red beet, Beta vulgaris, tonoplast as well as with another archaebacterial ATPase from Sulfolobus acidocaldarius. The affinity is much higher than to F1-ATPase from spinach chloroplasts or to Ca2+-ATPase from sarcoplasmic reticulum of rabbit skeletal muscle. PMID- 2892467 TI - Hantavirus disease. PMID- 2892469 TI - Retrograde flow in the internal mammary artery. AB - Thirty-two patients undergoing coronary artery bypass grafting were studied to evaluate retrograde flow in the internal mammary artery (IMA). The left IMA pedicle was prepared in routine fashion from the level of the first rib superiorly to just distal to the IMA bifurcation. Following cannulation for cardiopulmonary bypass but before institution of extracorporeal circulation, the IMA was divided 5 mm proximal to its bifurcation and allowed to bleed freely. The flow from each end was then measured by allowing the segment to bleed for 30 seconds. The mean antegrade flow was 73 +/- 34 ml/min, and the retrograde flow was 25 +/- 17.2 ml/min. The difference between the flows was significant (p less than 0.05). Based on these data we do not recommend the retrograde IMA technique as a primary form of revascularization of the myocardium. In selected circumstances it may be used if adequate retrograde flow is demonstrated before constructing the anastomosis. PMID- 2892468 TI - Incidence of perforated and bleeding peptic ulcers before and after the introduction of H2-receptor antagonists. AB - The incidence of perforated and bleeding peptic ulcer requiring emergency surgery was studied in a defined population before and after the introduction of histamine H2-blockers. The incidence of these ulcer complications was unchanged from 1974 to 1984 with an incidence of ulcer perforation from 4 to 10/100,000 per year and of bleeding ulcer from 5 to 10/100,000, indicating that the H2-blockers have not changed the incidence of severe ulcer complications. PMID- 2892470 TI - [Treatment of arterial hypertension. Clinical and pharmacological considerations]. PMID- 2892472 TI - Evidence for central alpha 2-adrenoceptor-mediated hypertension in freely moving, normotensive rats. AB - The hypertensive response mediated by central alpha 2-adrenoceptor stimulation was investigated in freely moving, normotensive rats with chronic arterial catheters and guide cannulas. The alpha 1-adrenoceptor agonists (methoxamine, phenylephrine, ST 587) and the alpha 2-adrenoceptor agonists (B-HT 920, clonidine, oxymetazoline) injected intravenously (i.v.) caused a rise in mean blood pressure. The rank order of potency of the agonists to produce 25 mm Hg of pressor response (the effective dose; ED25) was oxymetazoline (0.64 microgram/kg) greater than phenylephrine (1.05 microgram/kg) greater than clonidine (1.6 microgram/kg) greater than ST 587 (5.4 micrograms/kg) greater than B-HT 920 (19.0 micrograms/kg) greater than methoxamine (19.5 micrograms/kg). The intracerebroventricular (i.c.v.) injection of alpha 2-adrenoceptor agonists, B-HT 920 (3 to 300 micrograms/kg), clonidine (3 to 100 micrograms/kg) and oxymetazoline (3 to 100 micrograms/kg) produced a dose-dependent and long-lasting pressor response associated with bradycardia, without showing a significant depressor response for up to 90 min at any of the doses used. The i.c.v. injection of alpha 1-adrenoceptor agonists, methoxamine (100 to 500 micrograms/kg), phenylephrine (100 to 500 micrograms/kg) and ST 587 (100 to 300 micrograms/kg) produced a short-lasting pressor response with variable changes in heart rate. In addition, a significant long-lasting depressor response concomitant with a decrease in heart rate was observed 30-60 min after the injection at higher doses. Dose-response curves for pressor responses to alpha 2 adrenoceptor agonists were located to the left of those for alpha 1-adrenoceptor agonists. The rank order of potency of the agonists injected i.c.v. in producing pressor responses with ED25 was clonidine (12.0 micrograms/kg) greater than oxymetazoline (14.0 micrograms/kg) greater than B-HT 920 (16.0 micrograms/kg) much greater than ST 587 (125 micrograms/kg) greater than phenylephrine (235 micrograms/kg) greater than methoxamine (310 micrograms/kg). Central (i.c.v.) pretreatment with yohimbine (100 micrograms/kg) abolished hypertensive responses to centrally administered alpha 2-adrenoceptor agonists but the treatment with prazosin (30 micrograms/kg) was less effective in inhibiting the hypertensive responses. In pentobarbital-anesthetized rats, pressor responses to i.c.v. injection of alpha 1- and alpha 2-adrenoceptor agonists were significantly inhibited and a long-lasting depressor response was induced by alpha 2 adrenoceptor agonists, whereas depressor responses to alpha 1-adrenoceptor agonists were not affected.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2892471 TI - Comparison of the milk leakage potencies of adrenergic agonists in lactating cows. AB - The activities of epinephrine (2-6 micrograms) and of norepinephrine (20-60 micrograms) on the relaxation of teat sphincter muscles were compared by measuring milk leakage from the full udder of 5 lactating cows. Substances were injected into the external pudic artery after pretreatment with an alpha adrenoceptor blocking agent (prazosin or phentolamine). Milk leakage was induced by creating a vacuum (-30 cm of water) in a plethysmographic chamber enclosing one teat and volumes of milk loss were measured every min. In a second series of experiments the activities of the beta 2-adrenoceptor selective agonist zinterol (0.5-2.5 micrograms) and of the nonselective beta-agonist isoproterenol (3-22.5 micrograms) on sphincter muscle relaxation were compared. Epinephrine was found to be more potent than norepinephrine in inducing relaxation of sphincter muscles. Zinterol was more active than isoproterenol. It is concluded that there is a predominance of beta 2-adrenoceptors in the teat sphincters. PMID- 2892473 TI - SK & F 95018, a vasodilator/beta-adrenoceptor antagonist. AB - The pharmacological properties of a novel vasodilator/beta-adrenoceptor antagonist, SK & F 95018 6-[4-[3-(3-[4-(2-Cyclopropylmethoxyethyl)phenoxy]-2- hydroxypropylamino)propionamido]phenyl]-4,5-dihydro-5-met hylpyridazin- 3(2H)-one methanesulphonate] are described. SK & F 95018 lowered blood pressure and increased hindquarters blood flow in anaesthetised rats over the same dose range 1-5 mumol kg-1. Over a similar dose range SK & F 95018 inhibited isoprenaline induced tachycardia in ganglion-blocked, anaesthetized cats. SK & F 95018 had minimal effect on bronchial beta 2-adrenoceptors, while simultaneously antagonizing cardiac beta 1-adrenoceptors in anaesthetized guinea-pigs. SK & F 95018 was demonstrated to be a potent antihypertensive agent in conscious spontaneously hypertensive rats over the dose range of 1.6-13 mumol kg-1 i.v. and 13-103 mumol kg-1 p.o. A marked and persistent hypotension was observed in conscious cats at a dose of 7.5 mumol kg-1 i.v. and 19 mumol kg-1 p.o., without reflex tachycardia. In anaesthetized cats, the hypotensive response to the compound was found to be via a reduction in total peripheral resistance with a maintained cardiac output. Vasodilatation and beta-adrenoceptor antagonism have been demonstrated in the same molecule (SK & F 95018) in a combination which would be suitable for effective treatment of hypertension. PMID- 2892474 TI - [Entamoeba histolytica surface antigens that interact with specific human IgA immune sera]. PMID- 2892475 TI - [Nervous system involvement in HIV1 infections in infants]. AB - A prospective survey of 38 HIV1-infected infants has been performed. Thirty-four percent of the patients expressed neurological abnormalities. Three main clinical entities of various intensity have been defined: 8 patients had severe intellectual and motor dysfunctions associated with a bucco-lingual dyspraxia; in 4 patients, the intellectual and motor alterations were less intense but were associated with a severe bucco-lingual dyspraxia; finally one patient had no clinical symptomatology but a chronic lymphocytic meningitis. No opportunistic infection of the CNS was observed. The neurological alterations were correlated in intensity with the immunological dysfunction. CT scans were normal or showed cerebral atrophy in most cases. CSF were normal in 12 cases and a pleiocytosis was observed in one case. However, in 4 of the 6 tested cases, anti-HIV antibodies were detected in CSF. PMID- 2892476 TI - [Primary acrosyndrome. Treatment combining an alpha-blocked and a calcium blocker]. AB - Case-report of a 5 year-old girl presenting with primitive peripheral vascular disease. Treatment associated an alpha-blocker and a calcium blocker. Therapeutic efficacy was evaluated from the clinical improvement and thermographic studies. PMID- 2892478 TI - Significance of neuroleptic dose and plasma level in the pharmacological treatment of psychoses. AB - The clinical use of antipsychotic agents may be enhanced by considering their dose-effect characteristics. In particular, assessment of immediate and later follow-up treatment of psychotic patients (1) indicates that moderate doses are adequate for most patients, (2) fails to support the utility of unusually high doses, and (3) even suggests the existence of a biphasic relationship of antipsychotic efficacy to dose of neuroleptics and possibly to plasma concentrations of the drugs as well. Trends toward lesser overall clinical benefits of high doses may reflect untoward extrapyramidal or other central nervous system effects leading to behavioral and cognitive symptoms. Thus, moderate doses of neuroleptics appear, on average, to be about as effective as, and probably safer than, the larger doses that have been popular in the United States in recent years. PMID- 2892477 TI - Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. AB - Using positron emission tomography and the carbon 11-labeled ligand raclopride, central D2-dopamine receptor occupancy in the putamen was determined in psychiatric patients treated with clinical doses of psychoactive drugs. Receptor occupancy in drug-treated patients was defined as the percent reduction of specific carbon 11-raclopride binding in relation to the expected binding in the absence of drug treatment. Clinical treatment of schizophrenic patients with 11 chemically distinct antipsychotic drugs (including both classic and atypical neuroleptics such as clozapine) resulted in a 65% to 85% occupancy of D2-dopamine receptors. In a depressed patient treated with the tricyclic antidepressant nortriptyline, no occupancy was found. The time course for receptor occupancy and drug levels was followed after withdrawal of sulpiride or haloperidol. D2 dopamine receptor occupancy remained above 65% for many hours despite a substantial reduction of serum drug concentrations. In a sulpiride-treated patient, the dosage was reduced in four steps over a nine-week period and a curvilinear relationship was demonstrated between central D2-dopamine receptor occupancy and serum drug concentrations. The results demonstrate that clinical doses of all the currently used classes of antipsychotic drugs cause a substantial blockade of central D2-dopamine receptors in humans. This effect appears to be selective for the antipsychotics, since it was not induced by the antidepressant nortriptyline. PMID- 2892479 TI - Pharmacotherapy for patients with borderline personality disorder. PMID- 2892480 TI - Rat lymphoid cell lines with HTLV-I production. III. Transmission of HTLV-I into rats and analysis of cell surface antigens associated with HTLV-I. AB - Newborn WKA rats given a single intraperitoneal injection of MMC treated TARS-1, a rat T cell line producing HTLV-I, were shown to accumulate high titred antibodies specific for HTLV-I. Adult WKA rats rejected TARS-1 transplant with transient appearance of anti-HTLV-I antibodies. However, rats maintained under daily administration of Bredinin, an immunosuppressive drug after TARS-1 transplant showed continuous production of antibodies specific for HTLV-I by aging. Type-C virus particles similar to HTLV-I were demonstrated by electronmicroscopy in the short-term cultured spleen cells of these rats. The evidence indicates that HTLV-I can be transmitted into newborn and immunosuppressed adult rats and they may provide a suitable animal model of ATL and related conditions in man, especially for elucidating the virus-host interactions involved in the leukemogenesis of HTLV-I. By using monoclonal antibodies, cell surface antigens associated with HTLV-I were also analysed. PMID- 2892481 TI - Restriction endonucleases recognizing DNA sequences of four base pairs facilitate differentiation of herpes simplex virus type 1 strains. AB - Variation of restriction endonuclease cleavage patterns between herpes simplex virus type 1 (HSV-1) strains was investigated using restriction endonucleases recognizing DNA sequences of four base pairs (4-bp enzymes) (HaeIII, HhaI, Sau3AI). The analysis made feasible identification of variations not heretofore detectable, using enzymes recognizing DNA sequences of six base pairs (BamHI, KpnI, SalI), and proved to be most useful for distinction and classification of HSV-1 strains. Ten of the fifteen strains analysed using 4-bp enzymes were closely related, and were put into group 1, and the other five not so related strains were classed into the non-group 1. The observations suggested a possible common ancestor from which group 1 strains had derived. PMID- 2892482 TI - Differential effect of Bordetella pertussis on experimental posterior uveitis in the black-hooded Lister rat. AB - The effect of an additional adjuvant, Bordetella pertussis, on the clinical and histopathologic features of experimental autoimmune uveitis in black-hooded Lister rats was investigated. Disease was induced by a single footpad injection of purified retinal S-antigen in Freund's complete adjuvant. In those animals that did not receive B Pertussis the clinical features were those of a retinal vasculitis with disc edema, periphlebitis, and deep retinal infiltrates. In contrast, animals that received B pertussis developed lesions in the pigment epithelium and choroid. Histopathologic studies disclosed focal photoreceptor necrosis associated with mononuclear cell infiltration in both groups of animals. However, in the group that did not receive B pertussis the disease was predominantly a retinitis associated with perivascular infiltration of retinal vessels, whereas in the group that did receive B pertussis the main feature was a focal choroiditis, with superficial retinal lesions being rarely observed. Retinal photoreceptors were the target tissue in both groups of rats, but the route by which they were damaged was altered from predominantly retinal to choroidal by the addition of Bordetella pertussis as an adjuvant. This change may be ascribed to the ability of B pertussis toxin to sensitize vascular endothelium to local mast cell products, these cells being plentiful around choroidal vessels but absent in the retinal circulation. PMID- 2892483 TI - [The occurrence of rotavirus and fimbriae-bearing E. coli types in foals with diarrhea]. PMID- 2892484 TI - [Fimbriae formation, disease form and vaccination in infection with Salmonella typhimurium variatio copenhagen (STMVC)]. PMID- 2892486 TI - Decrease of the salt appetite of spontaneously hypertensive rats by chronic application of almitrine. AB - The effect of almitrine on salt appetite, water intake, and renal excretory function was investigated in conscious adult spontaneously hypertensive rats (SHR) of both sexes. The animals were kept singly in metabolic cages and given free access to food, water and 2.5% NaCl-solution. Oral administration of almitrine (0.4 mg/kg) for five days evoked an effective long-lasting suppression of voluntary salt intake and a temporary decrease of water intake. The pattern of renal electrolyte excretion was determined by the pattern of intake. The present results support the assumption that the activity of the peripheral arterial chemoreceptors plays an essential role in the maintenance of voluntary salt intake in SHR. PMID- 2892485 TI - Short-term effect of a high-protein/low-carbohydrate diet on aminopeptidase in adult rat jejunoileum. Site of aminopeptidase response. AB - The short-term effects of high-protein/low-carbohydrate diet on aminopeptidase N activity were studied in the brush-border membranes of proximal jejunum and proximal ileum of adult rats. The animals were starved overnight and re-fed for 15 h either with a standard diet (20% protein, 55% carbohydrate, in terms of energy content) or with a high-protein/low-carbohydrate diet of equal energy content (70% protein, 5% carbohydrate). All rats consumed similar amounts of diet, and measurements were made 15 h after initiation of re-feeding. In the proximal jejunum a slight increase in aminopeptidase activity was observed after the high-protein intake. In contrast, considerable stimulation (52%) of the enzyme specific activity was obtained in the proximal ileum. This increase in ileal aminopeptidase activity was more prominent in the mature cells of the upper villus. To determine if the increase of aminopeptidase activity was due to an increased amount of enzyme protein, rocket immunoelectrophoresis was performed with detergent-solubilized brush-border protein from ileum on agarose gels containing anti-(rat brush-border) antiserum. When the same amount of enzyme activity was loaded on the gels, the peaks of immunoprecipitate for aminopeptidase were similar for animals fed on a standard or a high-protein diet. When the same amount of protein was loaded, the peak of immunoprecipitate for aminopeptidase was higher (81%) after a high-protein diet. These results showed that the high protein intake evoked an increase in aminopeptidase activity, with a concomitant increase in the amount of immunoreactive protein. PMID- 2892487 TI - A zebrafish homeobox-containing gene with embryonic transcription. AB - A genomic library of zebrafish (Brachydanio rerio) was constructed and screened with homeobox-containing probes. One of the strongly cross-hybridizing clones was characterized by DNA sequencing. The deduced amino acid sequence exhibits extensive homology (greater than 80%) relative to the Antennapedia-class of Drosophila homeobox sequences. Characterization of the gene with respect to expression demonstrated that two transcripts of 2.1 and 1.4 kb, respectively, are present in embryonic poly (A+) RNA. The highest concentration of the two RNA species was observed in embryos which have terminated the process of somite formation. PMID- 2892488 TI - Frequency in hypertensives of alleles for a RFLP associated with the renin gene. AB - The genetic basis of primary hypertension is not known. Renin is important in blood pressure and volume control and a HindIII restriction fragment length polymorphism (RFLP) is present within the human renin gene locus. To examine whether there is a relationship between this RFLP and primary hypertension, DNA and renin analyses were performed on leukocytes and plasma from hypertensive and normotensive individuals. In hypertensives the frequencies of alleles for the HindIII RFLP were found to be 0.55 and 0.45, compared with 0.60 and 0.40 in the total population of 231 subjects examined, a difference that was not statistically significant. There also appeared to be no significant difference in renin activity in plasma for hypertensive patients of each genotype, nor in their pre- or post-treatment blood pressures. We thus conclude that, within the limits of the present study, the suspected genetic abnormalities associated with primary hypertension in man do not appear to be related to a HindIII RFLP in the renin gene. PMID- 2892489 TI - Molecular cloning of Escherichia coli K-12 ggt and rapid isolation of gamma glutamyltranspeptidase. AB - Based on the results of mapping of ggt, eight strains were selected from a gene library of E. coli. One of the strains harboring pLC9-12 was found to show 14 times higher gamma-glutamyltranspeptidase activity per cell than the wild type strain. The ggt was subcloned to the BamHI site of pUC18 and the recombinant plasmid pSH101 was obtained. Ggt- phenotype of gamma-glutamyltranspeptidase deficient mutants was complemented by pSH101. The specific activity of the enzyme in cells harboring pSH101 was 37-fold higher than that in the wild type cells. gamma-Glutamyltranspeptidase was isolated from the periplasmic fraction of the cells by simple two steps and crystallized. PMID- 2892490 TI - A magnesium-dependent guanylate cyclase in cell-free preparations of Dictyostelium discoideum. AB - Receptor-mediated regulation of guanylate cyclase is well-studied in intact Dictyostelium discoideum cells, but study of the enzyme in cell-free preparations has hampered. A major obstacle has been that in vitro guanylate cyclase activity could be detected only in the presence of unphysiological concentrations of Mn2+ ions. In this paper we report the identification of a guanylate cyclase in D.discoideum cell homogenates that has high activity with Mg2+-GTP. The enzyme is activated by non-hydrolyzable ATP and GTP analogues and inhibited by submicromolar concentrations of Ca2+-ions. We suggest that the presently identified enzyme is regulated in intact cells via cell surface receptors. The compounds that modulated the enzyme activity in vitro may reflect physiologically relevant regulation mechanisms. PMID- 2892491 TI - Membrane-stabilizing effect of vitamin E: effect of alpha-tocopherol and its model compounds on fluidity of lecithin liposomes. AB - The effects of vitamin E (alpha-tocopherol) and its model compounds on the fluidity of liposomes composed of dipalmitoylphosphatidylcholin (DPPC) and fatty acids were investigated by the measurement of the fluorescent polarization (P) using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a plobe. Although all tocopherols decreased the fluidity of liposomes which was perturbed by the inclusion of an unsaturated fatty acid having more than one double bond, alpha-tocopherol was more effective than the others. The fluidity in arachidonic acid-containing liposomes was decreased most in the presence of alpha-tocopherol and was decreased considerably by the inclusion of model compounds having a side chain at least one isoprene unit or a long straight chain instead of isoprenoid side chain. However, the chromanol with methyl group instead of the above side chain, and phytol, having no chromanol moiety, had no effect. These results show that a structural requirement for a membrane stabilization is to be either the chromanol moiety with methyl groups born on its aromatic ring or a side chain of appropriate length; an isoprenoid side chain of full length or one containing 4'a and 8'a-methyl groups is not necessarily needed. PMID- 2892492 TI - Amyloid beta-protein gene duplication is not common in Alzheimer's disease: analysis by polymorphic restriction fragments. AB - The amyloid beta-protein(BP) is an important component of amyloid fibrils of both Alzheimer's disease(AD) and adult Down syndrome(DS). It has been hypothesized that sporadic AD may involve the duplication of a subregion of chromosome 21 containing the BP locus. However, an improved method for detection of the BP gene duplication using polymorphic Hind III fragments led us to a conclusion that BP gene duplication is rare, if any, in (Japanese) sporadic AD patients, indicating that the duplication of the BP gene itself is not the common underlying genetic defect in AD. PMID- 2892493 TI - Amide proton exchange rates in cardioactive sea anemone polypeptides. AB - Amide hydrogen exchange rates have been measured using high-resolution 1H nuclear magnetic resonance (NMR) spectroscopy at 300 MHz for three homologous cardioactive polypeptides, anthopleurin-A from Anthopleura xanthogrammica and Anemonia sulcata toxins I and II. There are approximately 15 slowly exchanging hydrogens in each polypeptide, but the slowest exchange rates are found in ATX II, with ATX I and AP-A having rates similar to one another. The exchange rates correlate with the thermal stability of these molecules, but not with the potency and species specificity of their biological activities. The data for AP-A are interpreted in terms of a recent structural model for this polypeptide. PMID- 2892494 TI - Stereoselective delivery and actions of beta receptor antagonists. AB - These studies have revealed that the delivery and actions of beta receptor antagonist drugs are controlled by a cascade of stereoselective processes involving multiple enzymes, transport proteins and receptors. In essence, the free concentration of the pharmacologically active (-)-enantiomer species of these drugs presented to cell surface beta receptors appears to be a function of the stereoselective clearance by hepatic cytochrome P-450 isoenzymes, enantiomer selective binding to alpha 1-acid glycoprotein and albumin and perhaps predominantly by stereoselective sequestration (and release) by the vesicular amine transport protein within adrenergic neurons. Stereoselectivity in the clearance of beta blocking drugs, which can favor either the (+)- or (-) enantiomer, only appears to be important for the lipophilic drugs which are cleared by hepatic metabolism. Such stereoselectivity is due to differential stereochemical substrate requirements of individual hepatic cytochrome P-450 isoenzymes. Interindividual variations in the stereoselectivity can occur as a result of differences in the amount and expression of cytochrome P-450 isoenzymes due to genetic predisposition or other factors. In the same context, we have observed a significant correlation between the extent and stereoselectivity of binding of beta blocking drugs to plasma proteins. This is another finding which suggests that variability in the expression of individual proteins involved in the beta blocking drug-protein cascade determines the free concentration of the pharmacologically active enantiomer. However, since most observations have been made in young normal subjects, the extent of stereoselectivity in metabolism, binding and other processes is unknown in the general population where steady state plasma concentrations can vary widely due to multiple biological factors. The observations from neural studies support the concept that adrenergic nerve endings provide a depot for the stereoselective storage and release of the active enantiomer of beta receptor antagonists. The mechanism of this release appears to involve exocytotic secretion of drug that has been stereoselectively accumulated by the neurotransmitter storage vesicles. In terms of this idea, beta receptor antagonists released during nerve stimulation may achieve concentrations of the ( )-enantiomer within the adrenergic synapse greatly in excess of those found in plasma. Such a mechanism could significantly influence both the intensity and duration of beta receptor blockade in the heart, blood vessels, brain and other target tissues.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2892495 TI - Lysosomotropic behavior of adrenergic antagonists in interactions with human neutrophils. AB - Autonomic neurohormones affect the secretory activity of neutrophils by modulating release of lysosomal enzymes in response to immunologic stimuli. Autonomic agents are also weak bases which might modify cell function by accumulating in the acidic interior of the lysosome, in addition to their receptor-mediated activity. We examined the association of the beta-adrenergic antagonist [3H]dihydroalprenolol with human neutrophils and lysosome and membrane fractions derived from neutrophils, and the subcellular distribution of the photoaffinity-labeled beta-adrenergic ligand [3H]azidobenzylcarazolol after incubation with intact cells. Isolated neutrophil lysosomes accumulated significantly more [3H]dihydroalprenolol than isolated membrane preparations. Decreasing the transmembrane pH gradient markedly reduced [3H]dihydroalprenolol accumulation by intact cells or lysosomes but not by membranes. Since [3H]dihydroalprenolol accumulated by intact cells remained rapidly exchangeable, the photoaffinity ligand [3H]azidobenzylcarazolol was used to assess ligand distribution after association with whole cells. After cell disruption, 18.5 +/- 1.3% of this ligand appeared in the lysosome fraction as compared to 2.2 +/- 0.6% in the membrane fraction. The secretagogue phorbol myristate acetate caused release of the ligand as well as lysosomal enzymes from cells. These findings suggest that there is significant pH-dependent lysosomal accumulation of beta antagonists. This lysosomotropic interaction may be important both as it affects the sequestration and redistribution of the drugs, and as it might in some circumstances affect host defense functions of the neutrophil. PMID- 2892497 TI - Basolateral gamma-glutamyl transferase ectoactivity in rat liver: effects of chronic alcohol consumption. AB - Chronic alcohol consumption is known to increase hepatic gamma-glutamyl transferase (GGT) activity. The biological significance of this change has, however, remained unknown. Using a recently described methodology which allows the determination of basolateral ectoenzyme GGT activity (Ble-GGT) in perfused rat liver (Speisky et al, 1985), we have investigated the effects of chronic alcohol consumption on Ble-GGT and on its participation in the utilization of circulating glutathione (GSH). Ble-GGT was markedly increased (40-75%) by chronic alcohol consumption. The ecto-activity strongly correlated with total GGT activity, measured in whole liver homogenates from ethanol-fed animals (r = 0.898, p less than 0.001). Ble-GGT was found to catalyze the utilization of significant amounts of circulating GSH (7.4-14.7 nmol/min/100 g B.W.). Chronic ethanol treatment led to marked increases (111%) in the hydrolysis of circulating GSH, which highly correlated (r = 0.958, p less than 0.001) with total liver GGT activity. An increased Ble-GGT activity following chronic alcohol consumption might constitute a mechanism to increase the hepatic availability of GSH precursors. PMID- 2892496 TI - Histamine H2-receptor mediated activation of neonatal rat brain ornithine decarboxylase in vivo. AB - The effect of histamine (HA) administered via intracerebroventricular injection on ornithine decarboxylase (ODC) activity was studied in neonatal rat brain. The HA effect was dose and time dependent. Maximal increase in ODC activity was achieved 2 hr after administration of 10 micrograms HA (38% over control levels). Impromidine (HA H2-agonist) mimicked the effect of HA on ODC and ranitidine (HA H2-antagonist) inhibited the response to HA. Neither 2-thiazolylethylamine (HA H1 agonist) nor mepyramine (HA H1-antagonist) modified control ODC activity. The HA releasers, compound 48/80 and polymixin B sulfate, elicited an increase in brain ODC activity of 35% and 32%, respectively, over the control value. PMID- 2892498 TI - Influence of mouse genotype on responses on central neurotransmitters to long term alcohol exposure in striatum and hippocampus. AB - A striking strain dependency in response of central neuromediators (dopamine, serotonin, acetylcholine activities and somatostatin) to various periods of alcohol treatment has been noted in striatum and hippocampus in mice. For biogenic amines the C57Bl strain loses tolerance to prolonged alcohol injury earlier than the Balb/c strain. At the opposite the Balb/c strain exhibits a remarkable long lasting tolerance for cholinergic activity. The unequal capacity to adapt, also appears to depend on the nervous structure and the neurotransmitter considered. Such discrepancies may underly differences in behavioral changes observed in alcoholics. PMID- 2892500 TI - Effects of alcohol and acetaldehyde on metabolism and function of neurotransmitter systems in cerebral cortical neurons in primary culture. AB - Effects of alcohol (ethanol) and acetaldehyde (AcAl) on the metabolism and function of gamma-amino-butyric acid (GABA)ergic and cholinergic systems were investigated using mouse cerebral cortical neurons in primary culture. Exposure to alcohol in vitro had no significant effects on the content of neuroactive amino acids as well as the activities of glutamic acid decarboxylase (GAD), GABA transaminase (GABA-T), choline acetyltransferase (CAT) and acetylcholinesterase (AChE). In contrast, AcAl showed remarkable reductions of neuroactive amino acids content, and of CAT and AChE activities, but induced no alteration in the activities of GAD and GABA-T. [3H]Flunitrazepam [( 3H]FLN) binding and the stimulatory effect of GABA on [3H]FLN binding were found to be inhibited by in vitro exposure to both alcohol and AcAl, both of which, however, induced no changes in [3H]muscimol binding. These results suggest that the direct actions of AcAl on cholinergic systems in primary cultured neurons may be more potent than those of alcohol. The results described above also suggest that alcohol-induced neurochemical alterations in vivo may be, at least in part, caused by AcAl converted from alcohol in vivo. PMID- 2892499 TI - Combined antihistamine antagonism of the flushing reaction to alcohol. AB - The so-called Oriental flushing reaction associated with ingestion of small amounts of alcohol was antagonized by combined antihistamine administration. In stage one of the study, the flushing reaction to low doses of alcohol was produced in Orientals. Most subjects experienced a cutaneous flush, increase in skin temperature, decrease in blood pressure, increase in pulse rate and subjective symptoms such as dizziness, sleepiness, anxiety, headache, generalized weakness and nausea. One half of the group of subjects was then given diphenhydramine, 50 mg (H1 receptor antagonist) and cimetidine, 300 mg (H2 receptor antagonist) and the second half received placebo tablets before the administration of alcohol. The clearest difference between the antihistamine group and placebo group was in the skin flushing reaction. The antihistamine group showed a statistically significant reduction in the skin flush. The antihistamines also neutralized the systolic hypotension induced by the administration of alcohol. PMID- 2892501 TI - Short- and long-term components of working memory in the rat. AB - Previous experiments suggested that working memory of rats trained on a radial maze can be discussed in terms of its short- and long-term temporal components. For example, in Mizumori, Channon, Rosenzweig, and Bennett's (1985) study, long term working memory was found to be susceptible to disruption by the protein synthesis inhibitor anisomycin (ANI). In Experiment 1 of this report, we examined the neuropharmacological nature of short-term working memory of rats trained to retrieve food from all arms of a 12-arm radial maze. Delay intervals of varying length were placed between Choices 6 and 7. Lanthanum (LaCl3) and glutamate (GLU) injected bilaterally into the hippocampus effectively impaired retention over short delay intervals, which suggests a possible role for calcium and/or potassium and for glutamate in working memory. However, another equally likely explanation for the amnesic effects of LaCl3 and GLU is that these drugs impaired reference memory. To test more directly the hypothesis that LaCl3, GLU, or ANI might differentially affect working and reference memory, we tested the effects of these drugs on performance of rats trained to retrieve food from only 8 arms of the 12-arm maze in Experiment 2. The remaining 4 arms were never baited, in order to test reference memory function. We predicted that rats would make errors only in baited arms (i.e., errors of working memory). Instead, results of Experiment 2 showed that LaCl3, GLU, or ANI injection produced errors in unbaited arms even before a 120-min delay. If rats were injected with LaCl3 or GLU, baited arm errors were observed only after the delay period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892502 TI - The covalent structure of the elastase inhibitor from Anemonia sulcata--a "non classical" Kazal-type protein. AB - The amino-acid sequence of the proteinase inhibitor specific for elastases from the sea anemone Anemonia sulcata was determined from performic-acid oxidized inhibitor and from three cyanogen bromide fragments of reduced and carboxymethylated inhibitor. The molecule consists of a single polypeptide chain formed from 48 amino-acid residues and is stabilized by three intramolecular disulfide bridges. After cyanogen bromide cleavage of the native protein at methionines 10 and 28 followed by chymotryptic cleavage two fragments each containing a single disulfide bridge were isolated. These indicated the location of three intramolecular disulfide linkages between Cys4 and Cys34 (part of A loop), Cys8 and Cys27 (B-loop) and Cys16 and Cys48 (C-loop). The sequential homology and the disulfide pattern identified the elastase inhibitor as a Kazal type inhibitor in which, however, not only the CysI-CysII segment is rather short but interestingly the Cys4-Cys34 disulfide anchoring point (i.e. CysI-CysV) in the C-loop is shifted by one turn in the alpha-helical segment towards the C terminus. Thus, the elastase inhibitor is a non-classical Kazal-type inhibitor with respect to the positioning of the half-cystines. The inhibitor molecule was modelled based on the known three-dimensional structure of the silver pheasant ovomucoid third domain. The shortened amino-terminal segment was arranged in such a manner to allow disulfide bridge formation between the first cysteine Cys4 and the replaced Cys34 under maintenance of a suitable binding loop conformation. The characteristic ovomucoid scaffold consisting of a central alpha-helix, an adjacent three-stranded beta-sheet and the proteinase-binding loop cross connected through disulfide bridges CysI-CysV and CysIII-CysVI was conserved. PMID- 2892504 TI - Clinical trials of acellular pertussis vaccine in Sweden. An attempt to solve the problem of pertussis vaccination. PMID- 2892503 TI - Kinetic and thermodynamic analysis of taxol-induced polymerization of purified tubulin. AB - The kinetic and thermodynamic behavior of in vitro taxol-induced polymerization of purified tubulin has been studied. The assembly of tubulin initiated by taxol has a critical concentration of 0.1 mg/mL at 37 degrees C and consists of two consecutive pseudo first-order processes, a fast phase followed by a slow phase. The rate constants of the fast and slow phase polymerizations increase linearly with increasing tubulin concentration. This implies that the polymerization is a true pseudo first-order process. The ln (l/t0.5) of polymerization for both fast and slow phases follows a linear function with ln [tubulin] fulfilling one of the criteria of condensation polymerization mechanism. From the Arrhenius plot, the temperature dependence of the rate of tubulin polymerization in the presence of taxol is biphasic. The apparent activation enthalpies for the overall polymerization reaction are 13.0 and 50.8 kcal/mol (1 cal = 4.1868 J), respectively, above and below 26 degrees C. The apparent activation enthalpies for the elongation reaction have also been determined. The values are 11.6 and 28.4 kcal/mol above and below 28 degrees C. The temperature dependence of the equilibrium constants as revealed by the van't Hoff plot is also biphasic. The standard enthalpy and entropy values are delta H degrees = 7.4 and 22.5 kcal/mol above and below 30 degrees C, and delta S degrees = 50.3 and 101.0 cal/(deg.mol), at high and low temperatures, respectively. This suggests that the taxol-induced assembly of purified tubulin is a process driven by the effect of entropy. PMID- 2892505 TI - Non-toxigenic mutants of "Bordetella pertussis". PMID- 2892506 TI - A recombinant DNA approach to the pertussis vaccine. PMID- 2892507 TI - Local and systemic immune responses to pertussis infection and cellular and acellular vaccines. PMID- 2892509 TI - Purification and immunological characterization of bacterial and secreted adenylate cyclase of "Bordetella pertussis". PMID- 2892508 TI - Antigenic recognition of pertussis and cholera toxin by the same antipeptide antibodies. PMID- 2892510 TI - Characterization of fimbriae from "Bordetella" species. PMID- 2892511 TI - Cloning of a coding sequence of "Bordetella pertussis" filamentous hemagglutinin gene. PMID- 2892512 TI - Experimental models for testing "Bordetella pertussis" virulence and immunogenicity. PMID- 2892513 TI - Protective activities of "Bordetella pertussis" Tn5 mutants in mice. PMID- 2892514 TI - Identification of a pilus colonization factor that is coordinately regulated with cholera toxin. PMID- 2892515 TI - Advice for anaesthetists? PMID- 2892516 TI - The medical treatment of angina pectoris. PMID- 2892517 TI - Intrathecal sufentanil as a supplement to subarachnoid anaesthesia with lignocaine. AB - The combination of low-dose sufentanil with lignocaine for subarachnoid anaesthesia was studied in a double-blind comparative trial in 40 urological patients. Patients were allocated randomly to two groups and received 5% heavy lignocaine 1.5 ml together with either 1.5 ml of sufentanil 5 micrograms ml-1, or physiological saline 1.5 ml. No statistically significant differences were observed between the two groups with respect to analgesia or anaesthesia. The only clear benefit of the addition of a low dose of sufentanil to lignocaine was the significantly longer period of postoperative analgesia. There was no significant difference in the number of patients requiring supplementary analgesics. Side-effects were similar in both groups. PMID- 2892518 TI - Side effects and changes in pulmonary function after fixed dose precurarization with alcuronium, pancuronium or vecuronium. AB - On hundred and sixty premedicated patients undergoing surgery were assessed for changes in pulmonary function and signs of partial neuromuscular blockade following precurarization with a fixed dose of alcuronium 2 mg, pancuronium 1 mg or vecuronium 1 mg, and the efficacy of the drugs in the prevention of suxamethonium-associated side effects was compared. In this respect, no differences were observed between the three drugs. Pretreatment with alcuronium and pancuronium was followed by small decreases in pulmonary function. Statistically significant changes were seen only when vecuronium 1 mg was used as the fixed-dose precurarization agent. PMID- 2892519 TI - Vecuronium induced bradycardia following induction of anaesthesia with etomidate or thiopentone, with or without fentanyl. AB - To define the role of vecuronium in the occurrence of bradyarrhythmia, haemodynamic changes after the induction of anaesthesia were studied in 96 patients undergoing coronary artery bypass grafting. Patients were assigned to one of six groups according to different combinations of induction agents (etomidate 0.3 mg kg-1 or thiopentone 3 mg kg-1, with fentanyl 0.003 mg kg-1; etomidate 0.4-0.5 mg kg-1 or thiopentone 4-6 mg kg-1, without fentanyl) and neuromuscular blocking drugs (vecuronium 0.112 mg kg-1, pancuronium 0.112 mg kg-1 or suxamethonium 1 mg kg-1). Anaesthesia was maintained with enflurane and nitrous oxide in oxygen. After initial diverse changes, heart rate decreased in all groups. Thirty minutes after intubation, the reduction of heart rate showed statistically significant differences between the different combinations of drugs: fentanyl-etomidate-vecuronium (group I) (the largest reduction) greater than etomidate-vecuronium (II) = fentanyl-thiopentone-vecuronium (IV) greater than thiopentone-vecuronium (V) = fentanyl-thiopentone-suxamethonium (VI) = fentanyl-etomidate-pancuronium (III). Five patients in group I, two in group IV and one each in groups II and V had a heart rate slower than 45 beat min-1, whereas a similar value was never seen in groups III and VI. These results indicate that vecuronium has a bradycardic effect. This effect is more pronounced in association with etomidate than in association with thiopentone, and is augmented by the addition of fentanyl. PMID- 2892520 TI - Comparison of sedation with temazepam by mouth and diazemuls i.v. for dental surgery. Variability in absorption may influence clinical effect. AB - Temazepam elixir 30 mg by mouth was compared with i.v. Diazemuls titrated to a maximum dose of 20 mg in a double-blind study of 50 patients undergoing elective minor oral surgery. The treatments produced a similar reduction in anxiety score and similar degrees of patient relaxation and co-operation. The diazepam group had greater amnesia during surgery, but also showed significant slowing of reaction time at the time of discharge. Patients given temazepam elixir showed wide variations in plasma concentrations. Patients with low plasma temazepam concentrations at the time of surgery showed no significant reduction in anxiety scores. PMID- 2892521 TI - Effects of atracurium, vecuronium or pancuronium pretreatment on lignocaine seizure thresholds in cats. AB - Among the non-depolarizing neuromuscular blocking drugs, atracurium appears to be unique in its ability to produce cerebral stimulation in lightly anaesthetized animals. This effect is attributed to the atracurium metabolite, laudanosine. The following studies were performed to determine if pretreatments with the non depolarizing neuromuscular blockers pancuronium, atracurium or vecuronium would differ in their effects on the seizure threshold of lignocaine. Adult mongrel cats were anaesthetized with 1.0 MAC halothane in oxygen and nitrogen. Ventilation, blood-gas tensions, acid-base balance and temperature were controlled. Cats received pancuronium 0.2 mg kg 1 i.v. (n = 7), atracurium 1.0 mg kg-1 i.v. (n = 7) or vecuronium 0.2 mg kg-1 i.v. (n = 7). Ten minutes after the administration of the myoneural blocker, all cats received lignocaine 4 mg kg-1 min-1 i.v. until the onset of EEG evidence of generalized seizure activity. At seizure onset, there were no statistically significant differences among the cumulative lignocaine doses or the serum lignocaine concentrations in cats pretreated with pancuronium, atracurium or vecuronium. PMID- 2892522 TI - The feasibility of effective psychopharmacological treatments for alcoholism. PMID- 2892523 TI - Cognitive-behavioural treatment for benzodiazepine dependence: a comparison of gradual versus abrupt cessation of drug intake. PMID- 2892524 TI - Some characteristics distinguishing high and low dose users of benzodiazepines. PMID- 2892525 TI - Sulfhydryl modification and activation of phenylalanine hydroxylase by dinitrophenyl alkyl disulfide. AB - A new family of asymmetric thiol-disulfide exchange reagents, the dinitrophenyl alkyl disulfides (DNPSSR), was used to modify rat liver phenylalanine hydroxylase. The results indicate that the enzyme has two different types of reactive sulfhydryl (SH) residues per subunit. One SH residue was modified selectively by a DNPSSR having a neutral and hydrophilic alkyl group, and this modification was accompanied by appreciable activation of enzyme; the other SH residue was modified only by an anionic DNPSSR, and this modification did not result in activation. The catalytic properties of phenylalanine hydroxylase activated by DNPSSR were similar to those of the N-ethylmaleimide- (NEM-) modified enzyme, but the process of activation by DNPSSR was quite different from modification with NEM. An analysis of the reaction kinetics of the modification and of catalysis by the modified enzyme suggests that DNPSSR modification causes a change in the subunit interaction leading to a loss of the negative cooperativity normally seen with phenylalanine hydroxylase. PMID- 2892526 TI - Rapid increases in the transglutaminase activity of A431 cells following treatment with epidermal growth factor. AB - Transglutaminase activity was detected in lysates of A431 cells, a human epidermal carcinoma cell line. Enzyme activity was increased 1.5-2.5-fold in lysates prepared from cells pretreated with epidermal growth factor (EGF) relative to untreated control cells. Half-maximal activation of the transglutaminase activity occurred at 3-5 nM EGF, a concentration in good agreement with the Kd for EGF binding to its receptor in these cells. The increase in transglutaminase activity could be detected as early as 2 min after the addition of EGF, with the maximal response attained by 30 min. The activation was not blocked by pretreatment of the cells with cycloheximide, suggesting that the increased activity was not the result of an induction of transglutaminase synthesis. Fractionation of A431 cell lysates by centrifugation at 100000g for 30 min demonstrated that 90% of the transglutaminase activity was present in the soluble fraction and that this soluble transglutaminase activity was increased after treatment of the cells with EGF. The demonstration that EGF acutely increases the activity of a soluble, intracellular transglutaminase defines a novel pathway of growth factor action and provides a useful model system for identifying and comparing the mechanism(s) by which growth factors activate soluble enzymes. PMID- 2892527 TI - Subunit composition and ATP site labeling of the coated vesicle proton translocating adenosinetriphosphatase. AB - The partially purified proton-translocating adenosinetriphosphatase [(H+)-ATPase] from clathrin-coated vesicles has been reported to contain eight polypeptides of molecular weights 15,000-116,000 [Xie, X.S., & Stone, D.K. (1986) J. Biol. Chem. 261, 2492-2495]. To determine whether these polypeptides form a single macromolecular complex, we have isolated three monoclonal antibodies which recognize the reconstitutively active (H+)-ATPase in the native, detergent solubilized state. All three monoclonal antibodies precipitate the same set of polypeptides from either the partially purified enzyme or the detergent solubilized coated vesicle membrane proteins. The immunoprecipitated polypeptides have molecular weights of 100,000, 73,000, 58,000, 40,000, 38,000, 34,000, 33,000, 19,000, and 17,000. These results thus indicate that this set of polypeptides forms a single macromolecular complex and suggest that they correspond to subunits of the coated vesicle (H+)-ATPase. To identify the ATP hydrolytic subunit of the coated vesicle (H+)-ATPase, the purified enzyme was reacted with N-ethylmaleimide (NEM) and 7-chloro-4-nitro-2,1,3-benzoxadiazole (NBD-Cl), both of which inhibit activity in an ATP-protectable manner. Labeling was carried out by using [3H]NEM or [14C]NBD-Cl, and the specificity of the reaction was increased by prelabeling of the protein with the nonradioactive reagents in the presence of ATP and by taking advantage of the nucleotide specificity of protection. The principal polypeptide labeled by both [3H]NEM and [14C]NBD-Cl had a molecular weight of 73,000. In addition, this protein was the only polypeptide whose labeling was significantly reduced in the presence of ATP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892528 TI - Isolation and characterization of the human tyrosine hydroxylase gene: identification of 5' alternative splice sites responsible for multiple mRNAs. AB - A full-length genomic clone for human tyrosine hydroxylase (L-tyrosine, tetrahydropteridine:oxygen oxidoreductase, EC 1.14.16.2) has been isolated. A human brain genomic library constructed in EMBL3 was screened by using a rat cDNA for tyrosine hydroxylase as a probe [Brown, E. R., Coker, G. T., III, & O'Malley, K. L. (1987) Biochemistry 26, 5208-5212]. Out of one million recombinant phage, one clone was identified that hybridized to both 5' and 3' rat cDNA probes. Restriction endonuclease mapping. Southern blotting, and sequence analysis revealed that, like its rodent counterpart, the human gene is single copy, contains 13 primary exons, and spans approximately 8 kilobases (kb). In contrast to the rat gene, human tyrosine hydroxylase undergoes alternative RNA processing within intron 1, generating at least three distinct mRNAs. A comparison of the human tyrosine hydroxylase and phenylalanine hydroxylase [DiLella, A. G., Kwok, S. C. M., Ledley, F. D., Marvit, J., & Woo, S. L. C. (1986) Biochemistry 25, 743 749] genes indicates that although both probably evolved from a common ancestral gene, major changes in the size of introns have occurred since their divergence. PMID- 2892529 TI - Labeling of the ATP synthase of Escherichia coli from the head-group region of the lipid bilayer. AB - The isolated and membrane-bound forms of the adenosinetriphosphatase of Escherichia coli (ECF1 and ECF1F0, respectively) have been reacted with two lysine-specific reagents, sodium hexadecyl 4-[3H]formylphenyl phosphate (HFPP) and sodium methyl 4-[3H]formylphenyl phosphate (MFPP), and with the photoreactive reagent 1,2-[3H]dipalmitoyl-sn-glycerol 3-[[[(4-azido-2-nitrophenyl)amino]ethyl] phosphate] (arylazidoPE). HFPP and arylazidoPE are amphipathic molecules, inserting by their hexadecyl moieties (one and two chains, respectively) into the lipid bilayer, with the reactive groups intercalated among the phospholipid head groups. MFPP is the water-soluble analogue of HFPP. The labeling patterns of ECF1F0 obtained with HFPP and arylazidoPE were very similar; in both cases the a and b subunits of the F0 part were the most heavily labeled polypeptides of the complex. Models of subunit a, arranged in six transmembrane helices, place most of the lysines in the head-group region, available for reaction with HFPP. Subunits alpha and beta of the ECF1 part were very poorly labeled in comparison to the a and b subunits, together incorporating only 4% as much HFPP and 7.5% as much arylazidoPE as the two F0 subunits together on a protein mass basis. Trypsin cleavage studies localized any labeling of the alpha subunit by arylazidoPE to the N-terminal 15 residues of this polypeptide. When MFPP was used, the alpha and beta subunits were very much more reacted than the F0 subunits. This implies that most of the mass of the alpha and beta subunits in ECF1F0 is above the membrane and not in contact with the bilayer surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892530 TI - Kinetics and concentration dependency of cAMP-induced desensitization of a subpopulation of surface cAMP receptors in Dictyostelium discoideum. AB - Extracellular cAMP induces the rapid activation of guanylate cyclase, which adapts within 10 s to constant cAMP concentrations. A new response can be induced either by a higher cAMP concentration or by the same cAMP concentration at some time (t1/2 = 90 s) after removal of the previous stimulus. Stimulation of guanylate cyclase is supposed to be mediated by a subpopulation of cell surface cAMP receptors (B-sites). These sites can exist in three states, BF, BS, and BSS, which interconvert in a cAMP and guanine nucleotide dependent manner. It has been proposed that the transition of BS to BSS represents the activation of a guanine nucleotide regulatory protein [Van Haastert, P.J.M., De Wit, R.J.W., Janssens, P.M.W., Kesbeke, F., & DeGoede, J. (1986) J. Biol. Chem. 261, 9604-9611]. Binding of [3H]cAMP to these sites was measured after a short preincubation with an identical concentration of nonradioactive cAMP. [3H]cAMP could still bind to BF and BS, but not to BSS, indicating that the transition of BS to BSS is blocked by the preincubation with cAMP. This blockade was rapid and showed first-order kinetics with t1/2 = 4 s. A half-maximal blockade was induced by 0.7 nM cAMP; at this concentration only 5% of the B-sites are occupied with cAMP. The blockade of the transition of BS to BSS was released by two conditions: (i) When the concentration of cAMP was increased, the blockade was released within a few seconds. (ii) When cAMP was removed, the blockade was released slowly with t1/2 = 90 s.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892531 TI - Folate binding and transport by rat kidney brush-border membrane vesicles. AB - [3H]Pteroylglutamic acid (PteGlu) uptake was studied using brush-border membrane vesicles isolated from rat kidney. Results on the uptake of [3H]PteGlu by brush border membrane vesicles incubated in media of increasing osmolarities demonstrated that uptake was contributed by two components, intravesicular transport and membrane binding. Both the components of the uptake exhibited similar pH dependence, with maxima at pH 5.6, and were found to be saturable mechanisms with Km values of 6.7.10(-7) and 11.2.10(-7) M, respectively. These studies show that PteGlu is transported by isolated rat kidney brush-border membrane vesicles in a manner consistent with a saturable system and that a binding component may be functionally associated with this. PMID- 2892532 TI - Electrogenicity of sodium/L-glutamate cotransport in rabbit renal brush-border membranes: a reevaluation. AB - In order to clarify contradictory reports on the electrogenicity of sodium/L glutamate cotransport, this cotransport was studied using brush-border membrane vesicles isolated from rabbit renal cortex. Beforehand, the claim that the symport of L-glutamate with Na+ is linked to simultaneous antiport with K+ has been confirmed by the demonstration that equilibrium exchange of L-glutamate is inhibited by potassium. Concerning the electrogenicity of the system, the following results are reported: net uptake of sodium-dependent L-glutamate uptake was stimulated when the transmembranal electrical potential difference was increased by replacing a sodium sulfate gradient by a sodium nitrate gradient. At 100 mM Na+ the 'relative electrogenicity' of the initial uptake in the presence of intravesicular potassium was 2-times higher than in its absence. At a sodium concentration of 20 mM, when overall uptake was reduced, the relative electrogenicity in the presence of K+ was even 3-fold higher than in K+-free media. The relative electrogenicity of sodium/D-glucose cotransport measured under the same experimental conditions was not affected by K+. These results are discussed in terms of a model where the apparent electrogenicity of a cotransport system is dependent on the extent to which the charge translocating step is rate limiting ('rate limitancy'). It is proposed that potassium antiport, while decreasing charge stoichiometry of Na+/glutamate transport, increases the relative rate limitancy of the transport step translocating three cations (probably two Na+, one H+) together with one glutamate. Thereby the positive electrogenicity of glutamate uptake increases, in complete contrast to what would be expected from simple considerations of charge stoichiometry. PMID- 2892533 TI - Covalent incorporation of polyamines as gamma-glutamyl derivatives into CHO cell protein. AB - The possible role of polyamines in the covalent modification of proteins in CHO cells was investigated by metabolic labeling with [3H]putrescine. A single radiolabeled protein band with an apparent relative molecular mass of 18,000 Da was observed by SDS-polyacrylamide gel electrophoresis. Almost all the radioactivity covalently linked to this protein was recovered as hypusine. The labeling of this protein was increased several-fold when cells were cultured with alpha-difluoromethylornithine (DFMO) or with this drug plus methylglyoxal bis(guanylhydrazone) (MGBG), as a result of increase in specific radioactivity of the hypusine immediate precursor, spermidine. Also labeled under the latter condition were other cellular proteins. These were aggregates on the top both of the stacking gel and of the running gel, and protein-like materials with relative molecular masses of 36 and 8 kDa. The radioactivity covalently associated with these proteins was recovered after acid hydrolysis as polyamines. The identification of gamma-glutamylputrescine and gamma-glutamylspermidines in proteolytic digests of the acid-insoluble fraction of treated cells indicates that polyamines are covalently linked to these cellular protein. Several possible cellular functions of gamma-glutamylpolyamine protein components are discussed. PMID- 2892534 TI - Effect of orally administered 9-oxononanoic acid on lipogenesis in rat liver. AB - 9-Oxononanoic acid, which is one of the major products of the autoxidation of linoleic acid, was administered orally to rats and its effect on hepatic lipid metabolism was investigated. The de novo synthesis of fatty acids was strongly reduced 30 h after the administration of 100 mg of 9-oxononanoic acid as compared to that in the saline-administered group. Activity of acetyl-CoA carboxylase decreased by 60% and the activity of carnitine palmitoyltransferase increased by 35% in the test group. The level of triacylglycerols in serum was low and the level of free fatty acids remained unchanged. Thus, the administration of 9 oxononanoic acid decreased hepatic lipogenesis. It is generally believed that the reduction in lipogenesis is facilitated by a decrease in the NADPH level. The ratio of NADPH/NADP in the test group, however, became high as compared to that in the control group, and the activities of glucose 6-phosphate and isocitrate dehydrogenases increased. On the other hand, the levels of CoA derivatives, especially long-chain acyl-CoA, were higher in the test group than in the control. Therefore, the reduction of hepatic lipogenesis in the 9-oxononanoic acid group could be attributed to the inhibition of acetyl-CoA carboxylase by the accumulated long-chain acyl-CoA. PMID- 2892535 TI - Cyclic phosphorylation/dephosphorylation cascade in bovine brain coated vesicles. AB - Coated vesicles are involved in transport of membrane proteins between several intracellular membrane-bound compartments. These vesicles possess a specific 50 kDa protein which is phosphorylated and dephosphorylated by a coated-vesicle specific kinase and phosphatase. We studied this phosphorylation/dephosphorylation cascade system and show that the phosphorylation level of the 50-kDa protein is governed by the ATP/ADP ratio. PMID- 2892537 TI - [Mediator and modulatory systems of the autonomic ganglia]. AB - Autonomic ganglia are the complex functional systems within which the information coming through the preganglionic "input" is transformed and transferred to the postganglionic "output". The scientific papers of last years devoted to the investigation of the classical cholinergic and adrenergic and nowadays intensively investigated the so-called "noncholinergic-nonadrenergic" mediatory systems in autonomic ganglia are analysed in this review. The main classical and putative neurotransmitters, complex functional transmitter interactions and their role in the adaptive ganglionic transmission regulation in vivo are considered. The questions of modulatory processes in autonomic ganglia realizing with the help of regulatory peptides are under special consideration. PMID- 2892536 TI - [Molecular organization of glutamate-sensitive chemoexcitatory membranes of nerve cells. Comparative analysis of glutamate-binding membrane proteins from the cerebral cortex of rats and humans]. AB - The kinetics of 3H-L-glutamate binding to human brain synaptic membranes revealed the existence of one type of binding sites with Kd and Vmax comparable with those for freshly isolated rat brain membranes. The fraction of glutamate-binding proteins (GBP) was shown to contain three components with Mr of 14, 60 and 280 kD whose stoichiometry is specific for human and rat brain. All fractions were found to bind the radiolabeled neurotransmitter and to dissociate into subunits with Mr of 14 kD after treatment with-potent detergents (with the exception of the 56-60 kD component). Study of association-dissociation of GBP protein subunits by high performance liquid chromatography confirmed the hypothesis on the oligomeric structure of glutamate receptors which are made up of low molecular weight glycoprotein-lipid subunits and which form ionic channels by way of repeated association. Despite the similarity of antigen determinants in the active center of glutamate receptors from human and rat brain, it was assumed that the stoichiometry of structural organization of receptor subunits isolated from different sources is different. The functional role of structural complexity of human brain glutamate receptors is discussed. PMID- 2892538 TI - The neurobiological basis of eating disorders: some formulations. PMID- 2892539 TI - Platelet MAO in schizophrenics: relationship to symptomatology and neuroleptics. PMID- 2892540 TI - Reversal of helpless behavior in rats by putative 5-HT1A agonists. AB - This study is designed to measure effects of serotonin 1A (5-HT1A) agonists on escape deficits produced by inescapable shock in rats--a model of learned helplessness. Rats were first exposed to 60 inescapable shocks (15-sec duration, 0.8 mA, every 1 min +/- 15 sec), and 48 hr later, they were subjected to daily 15 min shuttle-box sessions (30 trials/day) on 3 consecutive days. Twice daily intraperitoneal injection of buspirone (total daily dose of 0.5 and 1 mg/kg), gepirone (0.06 and 0.125 mg/kg), 8-OH dipropylamino-tetralin (8-OH-DPAT) (0.03, 0.06, 0.125, and 0.25 mg/kg), and ipsapirone (TVXQ 7821) (0.03 and 0.06 mg/kg) eliminated escape failures. This indicates that an antidepressant-like effect- reversal of helpless behavior--can be obtained with drugs assumed to stimulate serotonin 1A receptors. PMID- 2892541 TI - Time course of schizophrenia and platelet 5-HT level. AB - The concentration of platelet serotonin (5-HT) and the simultaneous uptake of 5 HT into platelets have been investigated in schizophrenic patients with (A) intermittent time course of illness (complete remission), (B) chronic time course (partial remission and residual symptoms), and (C) intermittent-chronic time course (good remission at the beginning of illness with gradual progression to chronic stage). An increased platelet 5-HT concentration (i.e., hyperserotoninemia) of unknown etiology was observed, especially in the group with chronic time course of disease as compared to the normal controls. At the same time, kinetic constants Km and Vmax of 5-HT uptake into platelets were unchanged in all patients. Neuroleptic treatment did not produce any significant change either in platelet 5-HT level or in the uptake of 5-HT. These results provide further support for the possible 5-HT dysfunction in schizophrenia. PMID- 2892542 TI - Cortisol, ACTH, and dexamethasone concentrations in a psychogeriatric population. AB - Cortisol and adrenocorticotrophic hormone (ACTH) were measured at 2 time points before the administration of 1 mg of dexamethasone (day 1) and 1 time point on the following day (day 2). Thirteen severely depressed elderly patients, 15 patients with Alzheimer-type dementia (ATD), and 16 normal controls were studied. Cortisol was markedly elevated in depressed patients compared with the other subjects in day 1 samples. Following dexamethasone, both the depressed and ATD patients showed a similar elevation of cortisol compared with controls. ACTH concentrations were not significantly different between the groups before dexamethasone, but were significantly higher in both depressed and ATD patients after dexamethasone. More depressed patients than ATD patients exhibited hypersecretion of ACTH after dexamethasone. This implies that ACTH is less responsive to glucocorticoid feedback in elderly depressed patients, which may be a factor in causing hypercortisolemia. PMID- 2892543 TI - Tardive dystonia alternating with mania. PMID- 2892544 TI - Single-dose pharmacokinetics and bioavailability of famotidine in man. Results of multicenter collaborative studies. AB - Pharmacokinetics and bioavailability of famotidine, a new H2-receptor antagonist, were investigated in healthy subjects in five clinical studies. Linear pharmacokinetics were observed following either intravenous or oral administration. Plasma clearance averaged 463 ml min-1. Renal clearance averaged 310 ml min-1, which exceeded the glomerular filtration rate. Renal excretion was the major route of elimination. Urinary recovery of unchanged drug following intravenous administration was about 67 per cent. Famotidine plasma half-life was approximately 2.6 h. Oral absorption was incomplete. The bioavailability averaged 43 per cent of the dose. PMID- 2892545 TI - Etintidine-theophylline interaction study in humans. AB - Etintidine HCl is a potent H2-blocker. The effect of clinical doses of etintidine on the disposition of theophylline was investigated in 10 male volunteers. This was a double-blind, two-way crossover study. Each subject received etintidine (400 mg) or placebo twice a day with meals for 4 days on two occasions (separated by 4 days). On each occasion, the subjects were fasted overnight on Day 3 and were given an oral dose of theophylline elixir (5 mg/kg) 30 min following the administration of the morning dose of etintidine or placebo on Day 4. Blood samples were collected prior to and up to 24 h following the administration of theophylline. Plasma theophylline levels were analysed by HPLC. Theophylline was rapidly absorbed following oral administration of the theophylline elixir to both the placebo and etintidine treatment groups. Comparison of the pharmacokinetic parameters of theophylline between the etintidine and the placebo groups indicates that while etintidine did not significantly (p greater than 0.05) affect the apparent Cmax (11.1 vs 10.0 micrograms ml-1) and Tmax (1.7 vs 1.4 h) values of theophylline, etintidine significantly reduced the oral clearance (0.0200 vs 0.0564 l kg-1 h-1, p = 0.000006) and prolonged the elimination half life (16.8 vs 6.0 h) of theophylline. The data indicate that etintidine, like cimetidine, extended the elimination of theophylline in humans. PMID- 2892547 TI - [Interaction of the anxiolytic agent buspirone with serotonin and other synaptic receptors in the human brain]. AB - Buspirone and Mj 138-05 (up to 0.1 mM) did not displace specifically bound (3H) tryptamine, (3H) strychnine, (3H) flunitrazepam and (3H) imipramine in human cortical and hippocampal membrane preparations. At the same time both compounds displayed similar to serotonin affinity (IC50 in the range of 2-6 microM) for (125I)-LSD specific binding sites in the human cortex and hippocamp. IC50 of serotonin and buspirone and Mj 138-05 for (3H) LSD (2 nM) specific binding sites in the hippocamp was determined as 0.14 microM, 2.3 microM and 6.1 microM, respectively; and for (3H) serotonin specific binding sites in the hippocamp as 0.005 microM, 3.8 microM and 21 microM, respectively. The affinity for human cortex (3H) LSD binding sites was 10-fold lower in case of serotonin and 4-fold lower in case of buspirone and Mj 138-05 than in the hippocamp. However, the affinity for (3H) serotonin binding sites in the cortex was the same as in the hippocamp in case of serotonin and 12-15-fold lower than in the hippocamp in case of buspirone and Mj 138-05. It is concluded that in human brain buspirone and Mj 138-05 interact with micromolar affinity with 5 HT2 and are capable of binding to a subpopulation of 5 HT1 receptors in the hippocamp. PMID- 2892546 TI - [Effect of subchronic administration of phenazepam and synthetic antioxidants on the functional status of synaptic membranes in the cerebral cortex of rats subjected to prolonged stress]. AB - Monoamine oxidase activity, lipid peroxidation and membrane structure were tested after chronic stress and 7-day treatment with drugs in the brain cortex synaptosomal membranes of rats. The most potent corrector of stress-induced changes, as compared to hydrophobic antioxidant dibunol and tranquilizer phenazepam, was compound 3-OP, a hydrophilic antioxidant. PMID- 2892548 TI - Chemotherapy drug resistance--a panel discussion. AB - Considerable insight into the problem of drug resistance has emerged in the past few years. An understanding of why tumors develop drug resistance is now at hand both from theoretical points of view and from experimental and clinical data. Experimental models of drug resistance, particularly related to the surface P glycoprotein, have been remarkably successful in teaching us why tumor cells in culture develop resistance to common therapeutic agents. In this panel discussion, the clinical relevance of these and other proposed mechanisms will be examined, with the hope of providing an up-to-date overview on this exciting field. PMID- 2892549 TI - Selected ion monitoring analysis of monoamine metabolites in cerebrospinal fluid. Application to the study of in vivo effects of alpha 2-antagonists. AB - The technique of isotope dilution mass spectrometry has been used for the measurement of biogenic amine metabolites in cerebrospinal fluid (CSF). CSF samples were collected from rabbits treated with alpha 2-antagonists. The aim of our study was to determine the specificity of these drugs on the central nervous noradrenergic, dopaminergic and serotonergic activity as measured by the release of corresponding monoamine metabolites. 3-Methoxy-4-hydroxyphenylethylene glycol (MHPG) and vanilmandelic acid (VMA) were used as parameters for the noradrenergic activity, whereas homovanillic acid (HVA) and 5-hydroxyindole-3-acetic acid (5 HIAA) were employed to follow the dopaminergic and serotonergic activity, respectively. For the measurement of the biogenic amine metabolites a published GCMS method has been adapted. Samples of 200 microliters CSF were processed. Following addition of deuterated internal standards and acidification, extraction was carried out with ethyl acetate. Preliminary experiments with the analysis of MHPG using diethyl ether for extraction gave rise to emulsion formation and resulted in poor recoveries for MHPG and in irreproducibility problems due to a preferential extraction of non-labelled MHPG, effects which were not observed with ethyl acetate extraction. Derivatization was done with a mixture of pentafluoropropionic anhydride/pentafluoropropanol (or hexafluoroisopropanol) in order to derivatize both hydroxyl and carboxylic acid groups. The derivatization procedure was optimized for the analysis of 5-HIAA by carrying out a second reaction step with pentafluoropropionic anhydride alone in order to complete the derivatization for the indolic NH moiety. The molecular ions of the derivatized products were selected for detection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892550 TI - Aggregate cultures of foetal rat liver cells: development and maintenance of liver gene expression. AB - Rotation-mediated aggregate cultures of foetal rat liver cells were prepared and grown in a chemically defined medium. Their capacity for cellular organisation and maturation was studied over a culture period of 3 wk by using both morphologic and biochemical criteria. It was found that within each aggregate, distinct liver cell types were present and attained their normal, differentiated phenotype. Parenchymal cells formed small acini with a central lumen. Within the first 2 wk in culture, albumin and ferritin mRNA levels were maintained, while the alpha-fetoprotein mRNA levels decreased, and tyrosine aminotransferase (TAT) gene expression increased. No significant response to glucocorticoids was observed in early cultures, whereas after 3 wk a marked increase in TAT mRNA levels was elicited by dexamethasone and glucagon (additive stimulatory effects). The results show that foetal rat liver cells cultured in a chemically defined medium are able to rearrange themselves into histotypic structures, and display a developmental pattern of gene expression comparable to that of perinatal rat liver in vivo. This culture system offers therefore a useful model to study the development and function of liver cells. PMID- 2892551 TI - Anti-ATLA antibody in patients with leukemias with special reference to its relevance to blood transfusion. PMID- 2892552 TI - Postsynaptic alpha-adrenoceptor reserve and the shift of the concentration response curves to the right, as caused by the irreversible alpha-adrenoceptor antagonist phenoxybenzamine. AB - 1. The effect of different concentrations of phenoxybenzamine (0.1, 0.3, 1, 3, 10 and 30 nmoll -1) on the concentration-response curves to phenylephrine (a selective alpha 1-adrenoceptor agonist) and noradrenaline (a mixed alpha 1- and alpha 2-adrenoceptor agonist) was compared in two kinds of vascular tissue: dog saphenous vein (has both postsynaptic alpha 1- and alpha 2-adrenoceptors) and dog mesenteric and renal arteries--where only postsynaptic alpha 1-adrenoceptors have been shown to exist. 2. In the saphenous vein, where both alpha 1- and alpha 2 adrenoceptors coexist, at only one concentration of phenoxybenzamine, 3 nmoll -1, the concentration-response curve of noradrenaline was shifted to the right without a reduction of the maximum; and this shift was small (by 0.4 log units). 3. In tissues where only alpha 1-adrenoceptors exist postsynaptically (mesenteric and renal arteries) phenoxybenzamine never caused any shift of the noradrenaline concentration-response curves to the right without depressing the maximum effect. 4. In none of the tissues did phenoxybenzamine at any concentration shift the concentration-response curve of phenylephrine to the right without depressing its maximum. 5. All these results indicate that in the dog saphenous vein there is a 'false' alpha-adrenoceptor reserve for noradrenaline, since two kinds of receptors participate in the response to this amine. 6. The calculation of the occupancy-response relationship for the renal artery showed that 24% of the maximal response occurs when only 2% of alpha 1-adrenoceptors are activated and 50% of maximum at 9% occupation. However, for 95% of the maximal response an 83% occupancy is required. Similar values were calculated for the mesenteric artery. 7. Thus, the surplus alpha-adrenoceptors which is very large for a half-maximal response becomes smaller and smaller as the magnitude of the response increases and probably disappears at the 100% response level. 8. If we retain the original definition of 'spare receptors' - receptors in 'excess' of those required to produce a maximal response, we conclude, that there is no receptor reserve in the dog mesenteric and renal arteries. PMID- 2892553 TI - Human platelet beta 2-adrenoceptors: agonist-induced internalisation and down regulation in intact cells. AB - 1. The effect of isoprenaline (10 microM at 37 degrees C for 30 min) pretreatment on [125I]-(-)-pindolol ([125I]-(-)-Pin) binding to beta 2-adrenoceptors on intact human platelets has been examined. 2. By use of saturation analysis, maximal binding capacity (Bmax) of [125I]-(-)-Pin binding in control and treated cells was assessed in the presence of 1 microM (-)-propranolol or 1 microM (+/-)-CGP 12177 which were taken to represent total or cell surface beta-adrenoceptors respectively. Assay incubations were performed at 37 degrees C and 4 degrees C, the latter to prevent recycling of internalised receptors. 3. Isoprenaline treatment resulted in an identical, highly significant, loss of binding sites (approximately equal to 25%) defined by (-)-propranolol at both assay temperatures as compared to control cells. Binding sites identified in the presence of (+/-)-CGP 12177 were reduced to a much greater extent (approximately equal to 70%), but this was only seen when assays were performed at 4 degrees C. 4. Agonist-induced changes in receptor numbers were concentration-dependent with half maximal receptor loss occurring at an isoprenaline concentration of approximately 2 x 10(-8) M. These effects were inhibited by the presence of a beta-adrenoceptor antagonist and absent if agonist pretreatment was performed at 4 degrees C. 5. Recovery experiments showed that the isoprenaline-induced reduction in total receptor number defined by (-)-propranolol was irreversible whereas the reduction in cell surface receptors defined by (+/-)-CGP 12177 was rapidly reversible (less than 40 min). 6. These data suggest that isoprenaline treatment of intact human platelets causes redistribution of beta 2 adrenoceptors. A proportion are sequestered away from the cell surface (internalised), becoming inaccessible to the hydrophilic ligand (+/-)-CGP 12177. A smaller proportion defined by (-)-propranolol are apparently totally lost from the cell (down regulated). PMID- 2892555 TI - Sensory neuropeptide effects in human skin. AB - 1 Neuropeptides released from sensory nerves may account for cutaneous flare and wheal following local trauma. In 28 normal subjects we have studied the effects of four sensory neuropeptides given by intradermal injection on the forearm or back. 2 All peptides caused a flare distant from the site of injection, presumably due to an axon reflex. Substance P (SP) was the most potent (geometric mean dose causing 50% of maximum flare, 4.2 pmol). Neurokinin A (NKA) was the next most potent with neurokinin B (NKB) and calcitonin gene-related peptide (CGRP) the least. The distant flare response to SP, NKA and NKB was maximal at 5 min and disappeared within 2 h. 3 CGRP caused a local erythema over the site of injection at doses above 0.5 pmol which at higher doses lasted for up to 12 h. 4 SP, NKA and NKB caused wheals at doses above 5 pmol with SP and NKB being the most potent. CGRP (up to 250 pmol) did not consistently cause wheal formation. There was no significant effect of coinjection of CGRP upon the response to SP although there was a tendency for an enhancement of the wheal response. 5 The H1 histamine antagonist terfenadine (60 mg orally) significantly inhibited the wheal and distant flare response to histamine (5 nmol) and NKA, but not that caused by NKB. The distant flare of CGRP was also reduced but the local erythema was unaltered. 6. Aspirin (600 mg orally) significantly inhibited the distant flare response to SP, NKA and CGRP, but not that caused by NKB or histamine; the local erythema induced by CGRP was unaffected by aspirin. Aspirin also inhibited the wheal formed by NKA but not the wheal induced by the other substances. 7. These results suggest that tachykinins cause a distant flare response partially via the release of histamine and cyclo-oxygenase products, but cause a wheal by a direct effect on the skin microvasculature. The order of potency SP > NKB > NKA suggests that an SPp or NK, receptor is involved in the wheal response. CGRP by contrast has a direct vasodilator effect which is very prolonged. PMID- 2892554 TI - The effects of intraperitoneal administration of antagonists and development of morphine tolerance on the antinociception induced by stimulating the anterior pretectal nucleus of the rat. AB - 1 The effects of intraperitoneal administration of antagonists to morphine, 5 hydroxytryptamine (5-HT), noradrenaline and dopamine have been studied on the antinociceptive effects of electrical stimulation of the anterior pretectal nucleus (APtN) of the rat. 2 A 15 s period of 35 microA sine wave stimulation of APtN significantly increased the latency of the tail flick reflex to noxious heat for periods up to 1 h. 3 Naloxone (0.25-1.0 mg kg-1) attenuated the effects of APtN stimulation in a dose-dependent manner. In rats made tolerant to morphine by daily administration of morphine, the antinociceptive effects of APtN stimulation were significantly reduced. 4 The 5-HT receptor antagonists methysergide (5 mg kg 1) and ketanserin (1 mg kg-1), the dopamine receptor antagonist haloperidol (1 mg kg-1) and the beta-adrenoceptor antagonist propranolol (1 mg kg-1) had little effect on the antinociceptive effects of stimulating the APtN. 5 alpha Adrenoceptor antagonists caused a dose-dependent antagonism of the response. The order of potency was; idazoxan greater than prazosin greater than phenoxybenzamine, the respective ED50 for each drug being 0.08: 0.45: 1.5 mg kg 1. 6 It is concluded that antagonism at opioid receptors and alpha-adrenoceptors but not beta-adrenoceptors, dopamine or 5-HT receptors reduces the antinociceptive effects of APtN stimulation. This differs from the reported effects of these antagonists on the antinociception caused by stimulating other sites in the brain. PMID- 2892557 TI - Expressed emotion and relapse in first episodes of schizophrenia. A rejoinder to Macmillan et al (1986). AB - Re-analyses of data presented by Macmillan et al (1986b) challenge their conclusions that high expressed emotion is not prognostically significant for the course of schizophrenia or unrelated to the level of behavioural disturbance prior to admission. Several equally plausible models of causal relationships between EE and duration of untreated illness are presented. We conclude that our re-analyses of the Macmillan data do not warrant premature closure regarding the significance of the EE variable. PMID- 2892558 TI - Combination chemotherapy in rheumatoid arthritis. PMID- 2892556 TI - Independent regulation of beta 1- and beta 2-adrenoceptors. AB - 1 The down-regulation of beta-adrenoceptors has been postulated as a biochemical marker of antidepressant efficacy. Here we demonstrate that chronic treatment with desipramine down-regulates beta 1-adrenoceptors in rat cerebral cortex and that beta-adrenoceptor subtypes can be independently regulated by treatment with different beta-adrenoceptor agonists. 2 Desipramine, (+/-)-clenbuterol, prenalterol, corwin (20 mg kg-1 daily) and corwin (10 mg kg-1 daily) were administered to male, Sprague-Dawley rats, over eight days, by means of osmotic Alzet pumps placed subcutaneously and removed 24 h before analysis. Control rats received vehicle only. The beta 1- and beta 2-adrenoceptor populations were measured in cerebral cortex by a modified (-)-[125I]-pindolol receptor binding assay. 3 The conventional antidepressant, desipramine, preferentially down regulated beta 1-adrenoceptors whereas the non-selective beta-adrenoceptor agonist (+/-)-clenbuterol preferentially down-regulated beta 2-adrenoceptors. The beta 1-selective partial agonist, prenalterol, up-regulated beta 1-adrenoceptors perhaps acting more as an antagonist than as an agonist. Finally, neither dose of corwin had any significant effect on beta-adrenoceptor number. PMID- 2892559 TI - Sulphasalazine for palindromic rheumatism. PMID- 2892560 TI - Insulinoma and ganglioneuroma. PMID- 2892561 TI - Testicular torsion after previous orchidopexy. PMID- 2892562 TI - Neurotransmitters and psychosis. PMID- 2892565 TI - Tardive dyskinesia. PMID- 2892564 TI - Respiratory and allergic disease. II. Chronic obstructive airways disease and respiratory infections. PMID- 2892566 TI - Apolipoprotein B polymorphism and altered apolipoprotein B and low density lipoprotein cholesterol concentrations in Finnish children. PMID- 2892567 TI - Peptic ulceration. PMID- 2892563 TI - Respiratory and allergic disease. I. PMID- 2892568 TI - Amino acid neurotransmitter abnormalities in Huntington's disease and the quinolinic acid animal model of Huntington's disease. AB - Concentrations of gamma-aminobutyric acid (GABA), glutamate, aspartate, and taurine were measured in postmortem tissue from the brains of patients with Huntington's disease (HD) and in the quinolinic acid (QA) lesioned rat striatum. The aim of the study was to assess further the ability of the QA model of HD to reproduce the neurochemical features of the disease. Nine cortical and 9 subcortical regions were examined from 17 pathologically graded cases of HD and 10 controls. Significant reductions in both GABA and glutamate were found in HD striatum. The reductions were greater in the more severely affected grades of HD, and there was a gradient of amino acid loss across the striatal nuclei (caudate greater than putamen greater than nucleus accumbens) which was consistent with the known pattern of pathological involvement. Taurine and aspartate concentrations showed no significant change. GABA reductions were found in both segments of the globus pallidus (external greater than internal) and both parts of the substantia nigra (reticulata greater than compacta). In advanced cases of HD, there were significant reductions in glutamate in Brodmann cortical areas 3-1 2, 6, 9, and 17, but GABA, aspartate, and taurine were unaltered in the cortex. The QA lesions reproduced the striatal deficits of both GABA and glutamate but, in contrast to HD, there was a decrease in taurine, possibly due to species differences. Chronic QA lesions resulted in a secondary dying back of corticostriatal glutamatergic terminals, but did not produce a change in cortical glutamate concentration. This suggests that reductions in cortical glutamate in HD may reflect a primary loss of glutamatergic neurons. Our findings extend previous observations on amino acid neurotransmitters in HD and, with the exception of taurine, confirm the general applicability of the QA model. PMID- 2892570 TI - Bidirectional transfer between kindling induced by excitatory amino acids and electrical stimulation. AB - Chemical (C) kindling by means of repeated spaced injections into the amygdala (AM) of a subconvulsive dose of L-glutamate and L-aspartate combined in a molar ratio of 1:3. (Glu/Asp) produced progressive seizure development culminating in generalized convulsion strikingly similar to electrically kindled Stage 5 seizure in rats. These C-kindled AM sites responded readily to electrical stimulation with very rapid development of kindled seizure. When a separate group of rats electrically kindled at the AM were subjected to identical C-kindling at the kindled AM site, a similar positive transfer effect was observed. In addition, 30 days following the last injection, kindled Stage 5 seizure was triggered with a single injection of Glu/Asp, one-half of the dose used for C-kindling. These results suggest that the glutamate and/or aspartate systems participate in the development and persistence of increased seizure susceptibility induced by AM kindling. PMID- 2892569 TI - Differential effects of norepinephrine on hippocampal complex-spike and theta neurons. AB - The central noradrenergic system has long been postulated to modulate learning and memory. A brain structure known to be important in these functions is the hippocampus. Since the hippocampus receives a noradrenergic projection from the locus coeruleus, knowledge of norepinephrine's actions in the hippocampus may help determine its role in learning and memory. In the present study, the effects of norepinephrine were examined on two hippocampal cell types: complex-spike and theta-neurons. In the hippocampus, there is good evidence that complex-spike cells are pyramidal neurons, while theta-neurons are interneurons. Extracellular action potentials from hippocampal neurons were recorded using multibarrel glass micropipettes. Drugs were locally applied using pressure micro-ejection. Norepinephrine inhibited the spontaneous firing of complex-spike cells, while theta-neurons were excited. The inhibitory response of complex-spike neurons was mediated by an alpha 1-receptor. However, selective agonists for the alpha 2- and beta-noradrenergic receptors excited the complex-spike cells. The noradrenergic induced excitatory response of theta-neurons was also mediated by alpha 2- and beta-receptors. This study provides evidence that locally applied norepinephrine produces different responses on two types of hippocampal neurons. Furthermore, these differential responses arise primarily from the activation of distinct populations of noradrenergic receptors. PMID- 2892571 TI - The laminar distribution of amino acids in the caudal cerebellum and electrosensory lateral line lobe of weakly electric fish (Gymnotidae). AB - We have studied the distribution of the putative amino acid neurotransmitters glutamate, aspartate, gamma-aminobutyric acid (GABA), glycine, taurine and beta alanine in the caudal cerebellar lobe and electrosensory lateral line lobe (ELL) of weakly electric gymnotid fish. In the caudal lobe of the cerebellum, the levels of the various amino acids in the granular and molecular layers are comparable to the levels in the rat cerebellum, with the exception of taurine which is present in greater amounts in the gymnotid. In the ELL, these amino acids are differentially distributed in the various layers of this structure. Glutamate and taurine are enriched in the molecular layer, whereas GABA, aspartate, and beta-alanine are enriched in the deep neuropil + granular layers. Glycine is slightly enriched in the pyramidal cell layer. PMID- 2892572 TI - Alterations in regional concentrations of endogenous opioids following traumatic brain injury in the cat. AB - Delayed injury following trauma to the central nervous system (CNS) may be due to the release or activation of endogenous factors. Endogenous opioid peptides have been proposed as one such class of injury factors, based on pharmacological studies demonstrating a therapeutic effect of naloxone and other opiate receptor antagonists following CNS injury. However, changes in brain opioid concentrations following injury have not been evaluated. In the present study, we measured regional alterations in dynorphin (ir-Dyn), leucine-enkephalin (ir-Enk) and beta endorphin immunoreactivity (ir-End) following low- (1.0-2.0 atmospheres (atm)) or high- (3.0-4.0 atm) level fluid-percussion brain injury in the cat. A significant decrease in ir-End was observed in the hypothalamus at 2 h following high- but not low-level injury. No changes were observed in tissue ir-Enk following either level of injury. Severe brain trauma but not low-level injury caused a significant increase in ir-Dyn in the striatum, frontal cortex, parietal cortex, pons and medulla. In the anterior pituitary, a significant increase in ir-End and a significant decrease in ir-Dyn was observed at 2 h following both levels of injury. Pathological damage to brain tissue after injury was most pronounced in those regions showing significant increases in ir-Dyn but not other opioids. In the medulla, the increase in ir-Dyn but not ir-End or ir-Enk was also significantly correlated with a fall in systemic mean arterial pressure (MAP) at 2 h following high- but not low-level injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892573 TI - Intrathecal dynorphin(1-13) results in an irreversible loss of the tail-flick reflex in rats. AB - Intrathecal injection of dynorphin produced a loss of the tail-flick reflex that lasted throughout the 14-day experimental period whereas, the inclined plane test of motor function and tail-shock vocalization recovered within an hour. An important aspect of the loss of the tail-flick reflex was that it was an all-or none event. At any dose of tail-flick latency either remained unchanged when compared with pre-injection latencies or the latency was elevated to the cut off time of 14 s. The ED50's +/- S.E.M. for tail-flick, inclined plane and tail-shock vocalization were 65.4 +/- 5.0, 67.7 +/- 5.0 and 68.0 +/- 3.9 nmol respectively. Results from the hot-plate test revealed no statistical difference between saline and dynorphin injected animals one day following the injection. Animals injected with morphine sulphate s.c. lost the tail-flick reflex but completely recovered by 24 h. Histology of the spinal cord of animals treated with dynorphin 24 h prior to sacrifice revealed dead neurons primarily in the ventral horn with little or no damage in the dorsal horn. These data demonstrate that dynorphin(1 13) injected intrathecally results in a rather specific neurotoxic action in the spinal cord. PMID- 2892574 TI - Mu-, delta-, kappa- and epsilon-opioid receptor modulation of the hypothalamic pituitary-adrenocortical (HPA) axis: subchronic tolerance studies of endogenous opioid peptides. AB - In opiate-naive rats, the endogenous opioid peptides, beta-endorphin, dynorphin(1 13) and Met-Enk-Arg-Phe (MEAP) and the synthetic enkephalin analogue D-Ala2-D Leu5-Enk (DADLE) potently stimulated plasma corticosterone in a dose-dependent, naloxone reversible manner. To characterize their in vivo affinities, the effects of these peptides on plasma corticosterone release were tested in rats made tolerant to morphine, U50488H, DADLE/morphine or beta-endorphin. These cross tolerance studies showed that dynorphin and MEAP exerted their action on plasma corticosterone release at kappa-opioid receptors. The action of DADLE occurred at delta-opioid receptors, while the action of beta-endorphin occurred principally at another receptor site. These results indicate that there is independent modulation of the hypothalamic-pituitary-adrenal axis by endogenous opioid peptides at mu-, delta- and kappa-opioid receptors. In addition there may be modulation by beta-endorphin at a separate site that we suggest could be a central epsilon-receptor site. This cross-tolerance paradigm, using a neuroendocrine model, provides in vivo evidence for the action of centrally active endogenous opioid peptides at multiple and independent opioid receptors. PMID- 2892575 TI - Cardiovascular role of the major noradrenergic cell groups in the rabbit: analysis based on 6-hydroxydopamine-induced transmitter release. AB - We examined the role of the noradrenergic (NA) neurons of the A1, A2, A1 + A2, A5 and A6 + A7 regions on mean arterial pressure (MAP) and heart rate (HR), by comparing the acute responses of chronically lesioned and sham-operated rabbits to intracisternal 6-hydroxydopamine (6-OHDA, 600 micrograms/kg) which induces central release of transmitter. We studied rabbits (1) with intact arterial baroreceptors (non-denervated) and (2) after sino-aortic denervation (SAD). The acute transmitter release response consisted of an early fall in MAP (observed in SAD rabbits) and a late rise in MAP (observed in both non-denervated and SAD rabbits). Medullary lesions had no effect on either MAP component, but A5 and A6 + A7 lesions attenuated both pressor and depressor responses. Normally the transmitter release-induced MAP responses are modified by baroreceptor feedback. The 6-OHDA-induced HR changes were vagal in non-denervated rabbits and were sympathetically mediated in SAD rabbits. In non-denervated rabbits, A1, A2 and A1 + A2 lesions affected mainly the early vagal component, whilst A6 + A7 lesions affected the late vagal component. In SAD rabbits the early bradycardia was due to sympathetic inhibition and the late tachycardia due to sympathetic excitation; A1 + A2 lesions and A5 lesions attenuated the sympathetic bradycardia. We conclude that the various components of the MAP and HR responses are mediated through distinctive NA pathways; the deficits of a given lesion could be due to either to loss of NA cell bodies or of NA fibers of passage. PMID- 2892576 TI - Functional innervation of the striatum by ventral mesencephalic grafts in mice with inherited nigrostriatal dopamine deficiency. AB - Weaver mutant mice are characterized by a decrease in striatal dopamine (DA), which is associated with a progressive loss of DA neurones in the substantia nigra. This mutant thus provides the opportunity to examine the functional effects of DA neurones grafted to the striatum in a genetic model of parkinsonism. Ventral mesencephalic tissue from normal foetuses was placed on the surface of the right dorsal striatum of adult weaver mutants. After grafting, animals were tested for methamphetamine-induced circling behaviour. Mutants with DA containing grafts displayed a significant circling bias toward the left, non grafted side. Mutants without grafts did not display any rotational bias to either side. These results demonstrate that grafted DA containing neurones establish a functional innervation of the weaver striatum and suggest that grafting of neural tissue is a viable approach in restoring function in genetic degenerative disorders of the nigrostriatal system. PMID- 2892577 TI - Excitatory and inhibitory effects on respiration of L-glutamate microinjected superficially into the ventral aspects of the medulla oblongata in cat. AB - L-Glutamate (4-40 nmol) was microinjected at superficial depths beneath the ventral surface of the medulla oblongata in cats. Injections (100-300 microns beneath the surface) made rostromedial to the hypoglossal nerve, less than 1.5 mm lateral to the pyramidal tract, caused stimulation of phrenic nerve activity. Injections (100-500 microns beneath the surface) up to 1 mm further lateral caused a marked increase in arterial pressure and depression of phrenic nerve activity. These findings support the existence of two cell groups in the ventral medulla that are involved in regulation of respiration; when activated, one (medial group) causes facilitation and the other (lateral group) inhibition of respiration. PMID- 2892578 TI - Stimulation of the perforant path alters hippocampal levels of opioid peptides, glutamine and GABA. AB - This investigation demonstrates that stimulation of the perforant path under conditions which elicit wet dog shakes in rats produces a significant decrease in hippocampal levels of methionine-enkephalin, dynorphin A(1-8) and glutamine, and an increase in gamma-aminobutyric acid (GABA). Levels of these substances are not altered by stimulus parameters insufficient to elicit wet dog shakes. These results lend support to the notion that endogenous opioid peptides play a role in regulation of hippocampal excitability but may only be released under relatively intense stimulus conditions. The increase in GABA levels could be due to an increase in synthesis, an increase in reuptake or a reduction in release. The latter possibility is consistent with reports that iontophoretically applied enkephalin exerts its apparent excitatory effects via an inhibitory action on inhibitory neurons in the hippocampus. PMID- 2892579 TI - Hemicholinium-3 facilitates the release of acetylcholine by acting on presynaptic nicotinic receptors at a central synapse in Aplysia. AB - The effects of hemicholinium-3 (HC-3) on acetylcholine (ACh) release were studied on central inhibitory or excitatory synapses of Aplysia californica. HC-3 was used at concentrations below 10(-5) M, which did not affect choline uptake by this preparation. Statistical analysis of the synaptic noise evoked by sustained depolarization of the presynaptic neuron allowed us to calculate the amplitude and mean duration of the miniature postsynaptic responses at an inhibitory synapse in the buccal ganglion. Taking into account the modifications of miniature and evoked responses, it was concluded that HC-3 potentiates ACh release. A similar presynaptic effect was observed at an excitatory synapse in the abdominal ganglion. This facilitation of ACh release was prevented by tubocurarine or hexamethonium, pointing to an agonistic action of HC-3 on nicotinic presynaptic receptors implicated in a positive feedback on ACh release. The possible blockage of muscarinic presynaptic receptors by HC-3 was also considered. Hemicholinium-15 was without effect on ACh release but was nevertheless able to prevent the presynaptic action of HC-3. PMID- 2892580 TI - Serotonin axon terminals in the ventral tegmental area of the rat: fine structure and synaptic input to dopaminergic neurons. AB - The serotoninergic (5-hydroxytryptamine, 5-HT) innervation of the rat ventral tegmental area (VTA) was examined by light and electron microscopic radioautography following intraventricular infusion of [3H]5-HT. The [3H]5-HT labeled processes were characterized with respect to their regional distribution, ultrastructure and relationships with all neurons, including dopaminergic neurons, identified in the same sections using immunocytochemistry for the localization of the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH). By light microscopy, [3H]5-HT labeled axons and axonal varicosities were detected throughout the interfascicular nucleus and ventral portion of the VTA. By electron microscopy, [3H]5-HT-labeled axons were found to be mainly small and unmyelinated, although a few showed several lamellae of myelin. The labeled varicosities measured 0.6 micron in mean diameter and contained many small, round or flattened agranular vesicles and a few large granular vesicles. More than 18% showed synaptic specializations in single thin sections. Most of these synapses were asymmetric and established on dendritic shafts. Based on the probability of seeing such synaptic specializations in single thin sections, it was estimated that as many as 50% of the labeled 5-HT terminals formed synaptic contacts in the VTA. In dually labeled light microscopic sections, [3H]5-HT-accumulating processes often appeared adjacent to TH-immunoreactive perikarya and proximal dendrites. Electron microscopy demonstrated that terminals with radioautographic labeling for 5-HT formed conventional synapses both with TH-labeled and unlabeled dendrites in the VTA. Many additional 5-HT terminals lacking recognizable synaptic densities were directly apposed to TH-labeled dendrites and were isolated from the rest of the neuropil by thin glial leaflets. These results suggest that 5-HT neurons innervate both dopaminergic and non-dopaminergic neurons in the VTA and may influence mesocortical and mesolimbic efferent systems through synaptic as well as non-synaptic mechanisms. PMID- 2892581 TI - Glutamate suppression of feeding and the underlying output of effector neurons in Helisoma. AB - This study tested the consequences of 3 stress conditions on feeding consumption in the freshwater snail Helisoma. Two stresses (placement in a hypotonic environment and body wall incision) were without effect on food consumption. In contrast, placement of animals in a hypertonic environment (20% seawater) caused a transient suppression of feeding. Since the osmolarity and composition of molluscan blood is known to be altered under conditions of osmotic stress, we reasoned that a blood-borne agent might be responsible for the observed suppression of feeding. We tested this hypothesis by chromatographic analysis of blood and, based on this analysis, subsequent assay of putative neuromodulatory agents on the patterned motor activity (PMA) expressed by effector neurons of the buccal ganglion. Our analysis shows that a rise and fall of blood acidic amino acids corresponds to the suppression of feeding. Furthermore, bath application of glutamate at its elevated physiological level (100-150 microM) to buccal ganglia caused complete and prolonged suppression of PMA in effector neurons. This suppression is attributable to activation of chloride and potassium currents which shunt patterned synaptic inputs to the effector neurons. We conclude that glutamate, in an endocrine-like fashion, can exert a powerful neuromodulatory action on the feeding effector neurons of Helisoma. PMID- 2892582 TI - The blood pressure responses of thiazide-resistant hypertensives to a once-a-day bevantolol regimen. AB - The antihypertensive efficacy of a single daily dose of bevantolol (200 mg) alone or in combination with hydrochlorothiazide (25 mg) has been compared against conventional twice daily propranolol (80 mg) therapy in a group of 22 hypertensive patients whose blood pressures did not respond to thiazide monotherapy. Addition of bevantolol to the diuretic resulted in a significant (P less than 0.001) fall in sitting blood pressures (144/97 to 137/90 mmHg), supine blood pressures (147/100 to 141/92 mmHg) and heart rate (83 to 73 beats/min) 24 h after administration. When the diuretic was withdrawn, heart rate and diastolic pressures remained unchanged and within normotensive limits but systolic pressures increased to pre-treatment levels. Substitution of propranolol for bevantolol gave results comparable to the combined bevantolol-diuretic regimen except that heart rate was still lower (66 beats/min). No significant adverse reactions were reported. In thiazide-resistant hypertensives, a once daily dose of 200 mg bevantolol effectively reduced diastolic blood pressures towards normotensive limits and to an extent comparable with twice daily propranolol therapy. PMID- 2892583 TI - Gene mapping of X-linked choroideremia with restriction fragment-length polymorphisms. AB - Choroideremia is a sex-linked chorioretinal disorder that causes blindness in affected males. The gene for choroideremia has recently been localized by means of recombinant DNA technology to a region of the X chromosome, Xq13-22. We have used two DNA probes, both specific for this region, to study three affected families. The results of linkage analysis of restriction fragment-length polymorphisms (RFLPs) revealed by these probes suggest that in the three families the gene for choroideremia may not be as closely linked to the region of the X chromosome as was previously reported. The estimated degree of linkage between an informative RFLP and the disorder should be considered before predictive testing is offered to people at risk in affected families. PMID- 2892584 TI - Multiple actions of cadmium on transmitter release at the mouse neuromuscular junction. AB - The action of cadmium ions on transmitter release was studied at the neuromuscular junction in mouse diaphragm. In the presence of raised K+, Cd2+ caused a parallel shift to the right of the graph of transmitter release rate (frequency of miniature end-plate potentials, fmepp) versus log [Ca2+], with no change in maximum or slope, indicating a competitive mode of action of Cd2+. The apparent dissociation constant for Cd2+ was 3 microM. In calcium-free solutions containing 15 mM K+, Cd2+ caused a rise in the fmepp, which subsequently slowly declined despite the continued presence of Cd2+. The rise in fmepp caused by Cd2+ could be interrupted, but not reversed, by washing out the Cd2+ with EDTA. Exposure of the preparation to 100 microM Cd2+ for 15 min or more resulted in a raised fmepp that persisted despite the removal of Cd2+ and exposure to 200 microM EDTA. Following such treatment, the graph of fmepp versus log [Ca2+] continued to be shifted to the right. The interaction of Ca2+ with the residual effect of Cd2+ indicates that Cd2+, in addition to its action to block Ca2+ entry into the terminal, may act as a competitor and perhaps as a partial agonist at intracellular sites that normally bind Ca2+ and govern transmitter release. If this is the case, then it must be supposed that, in raised K+, quantal release of transmitter represents intermittent intense activation of release sites with local high levels of Ca2+ rather than continuous low level activation. PMID- 2892585 TI - Hepatocyte initiation during continuous administration of diethylnitrosamine and 1,2-sym-dimethylhydrazine. AB - Hepatocyte initiation, as indexed by growth-selected gamma-glutamyl transferase positive foci, was measured during continuous exposure to diethylnitrosamine (DEN) at concentrations used in previous DEN bioassay, DNA adduct, and cell replication studies. Hepatocyte initiation increased in a dose- and lobe-specific manner. The efficiency of DEN as an initiating agent was not affected by DEN dose rate over concentrations ranging from 4 to 40 ppm. In a similar experiment the initiating abilities of 1,2-sym-dimethylhydrazine and DEN were compared under continuous exposure regimens. Foci induction increased in a lobe- and time dependent manner. When left and median lobes were compared, the initiating ability of the two compounds correlated with their carcinogenicity. However, when corresponding anterior lobes were compared, no such correlation was observed. PMID- 2892586 TI - Coexistent tardive dyskinesia and parkinsonism. AB - Forty-six patients with tardive dyskinesia (TD) were studied to characterize the relationship between TD and parkinsonism. In two patients idiopathic parkinsonism (PD) preceded the use of neuroleptic drugs and in 15 patients TD was associated with drug-induced parkinsonism. Patients with TD alone were compared with patients who had the combination of TD and parkinsonism. Only age at onset of TD symptoms differentiated between the two groups (p less than 0.02); patients with associated parkinsonism had onset of TD later than patients with TD alone. Patients with PD may develop TD and the latter may be triggered by levodopa. When TD and parkinsonism are combined, the symptoms may be controlled by a careful use of dopamine depletors and levodopa. PMID- 2892588 TI - [Gamma-glutamyltransferase activity in amniotic fluid in fetuses with chromosome abnormalities and hereditary metabolic defects]. PMID- 2892587 TI - Immunocytochemical localization of aminopeptidase N on the cell surface of isolated porcine thyroid follicles. AB - The ultrastructural location of aminopeptidase N on the cell surface of isolated porcine thyroid follicle cells was studied with immunocytochemistry using antibodies against intestinal aminopeptidase N and protein A-colloidal gold. Gold particles, indicating immunoreactivity, were selectively attached to the apical cell surface. Occasionally, there was a sparse labelling of the basal cell surface. In follicles kept at 4 degrees C most gold particles at the apical cell surface appeared as clusters, with each gold particle situated at a constant distance of about 20 nm from the membrane surface. The gold particles were concentrated on the membranes of microvilli, in comparison to the smooth (intermicrovillar) portions of the apical plasma membrane. In follicles incubated at 37 degrees C for 5-180 min gold particles were slowly internalized by predominantly smooth-surfaced micropinocytic vesicles and subsequently appeared in colloid droplets and lysosomes. Gold particles were not observed in Golgi cisternae. TSH did not appear to influence the rate of internalization. TSH induced pseudopods were unlabeled. Our electron-microscopic observations confirm previous immunofluorescence-microscopic evidence that aminopeptidase N is selectively expressed in the apical plasma membrane domain in the thyroid follicle cell. Furthermore, aminopeptidase N appears to be distributed in microdomains within the apical plasma membrane. Earlier indications of molecular differences between the pseudopod membrane and the apical plasma membrane proper are further emphasized. PMID- 2892589 TI - Radioreceptor assay for a new antiallergic agent, 1-(2-ethoxyethyl)-2-(4-methyl-1 homopiperazinyl)benzimidazole difumarate (KB-2413), in plasma. PMID- 2892590 TI - Binding characteristics of 125I-iodocyanopindolol to beta-adrenergic receptors: biphasic Scatchard plots. II. Effects of selective antagonists. PMID- 2892591 TI - [Study on the morphometry of giant platelets in the peripheral blood of patients with epidemic hemorrhagic fever]. PMID- 2892592 TI - Stable phenotypic expression of glutathione S-transferase placental type and unstable phenotypic expression of gamma-glutamyltransferase in rat liver preneoplastic and neoplastic lesions. AB - Using immunohistochemical demonstration of glutathione S-transferase placental type (GST-P) and histochemical demonstration of gamma-glutamyltransferase (gamma GT), the long-term development of preneoplastic and neoplastic lesions was followed in rats over a 50-week period. Rats were given a single i.p. injection of 200 mg/kg body weight of diethylnitrosamine (DEN), and then 2 weeks later were administered 0.02% 2-acetylaminofluorene (2-AAF) (group 1), 0.05% phenobarbital (PB) (group 2), 2.0% butylated hydroxyanisole (BHA) (group 3) or no supplement (group 4) in their diet for 6 weeks, all rats being subjected to partial hepatectomy at week 3. Hepatocellular proliferated lesions were classified as foci, nodules and hepatocellular carcinomas. Development of foci, nodules and hepatocellular carcinomas was enhanced strongly by 2-AAF and weakly by PB, and inhibited by BHA. Almost all foci and nodules were GST-P positive, although 5-10% of the GST-P-positive foci were gamma-GT negative. The areas of GST-P-positive foci and nodules increased with time in all groups. In contrast, while the areas of gamma-GT-positive lesions also increased with time in groups 2-4, they decreased from week 12 in group 1. As the percentage gamma-GT-positive area in GST-P-positive foci significantly decreased with time in all groups, the rate of phenotypic reversion of gamma-GT in foci in group 1 was revealed to be larger than the focus growing rate, whereas that in groups 2-4 was smaller. Gamma-GT negative and GST-P-positive micro-nodules of altered morphology appeared within gamma-GT- and GST-P-positive nodules in later stages. All hepatocellular carcinomas found in this experiment consisted of GST-P-positive cells. In contrast, 37% (13/35) of the hepatocellular carcinomas were negative for gamma GT. The results indicate GST-P to be the most accurate marker enzyme for detection of initiated cells during liver carcinogenesis and gamma-GT to be more appropriate for indicating changes of phenotypic expression in each lesion type. PMID- 2892594 TI - Effect of two anticoagulants on leukocyte yield and function, and on lysosomal enzyme activity. AB - We compared acid citrate-dextrose (ACD-B) and heparin to determine which anticoagulant better preserves leukocytes for lysosomal enzyme assays if processing was done immediately or delayed for 24 h or more. Twenty normal subjects had blood drawn into tubes containing either ACD-B or heparin. The leukocytes were isolated by sedimentation in dextran (50 g/L) less than 2, 24, 48, and 72 h later. The most apparent difference was that cell counts indicated a 30% reduction in the number of leukocytes for ACD-B and a 95% reduction for heparin-treated cells at 48 h. The neutrophil function assay indicated that leukocyte processing must be done in less than 24 h regardless of the anticoagulant used, and that heparin is to be preferred. A comparison of heparin and ACD-B for maintenance of the activity of arylsulfatase A (EC 3.2.6.1) and hexosaminidase (EC 3.2.1.50) indicates that there is no effect of anticoagulant. However, at 48 h after venipuncture, there is an 80% reduction in the number of heparin-treated samples that are suitable for use in the assay. Those laboratories doing lysosomal enzyme tests on mailed specimens, which are most often greater than 24 h old, should use ACD-B as anticoagulant. PMID- 2892593 TI - Differential H1- and H2-receptor-mediated histamine responses of canine epicardial conductance and distal resistance coronary vessels. AB - The contributions of histamine (H1 or H2) receptor-mediated responses and, therefore, the effects of histamine blocking agents are unclear with regard to regulation of proximal epicardial and distal resistance coronary arteries. This study was designed to evaluate the effects of selective H1- and H2-receptor antagonists on epicardial and resistance vessels in the closed chest dog model. Histamine, diphenhydramine (H1 blocker), and cimetidine (H2 blocker) were infused into the left anterior descending coronary artery (LAD), and responses were studied by quantitative coronary angiography and flow measurements (133Xe washout). Histamine infusion alone produced a significant dilation of the proximal LAD (13% above control) only at the highest dose (45 micrograms/min), while LAD flow was increased by 128%. In the presence of H1 blocker, histamine produced significantly greater epicardial dilation (55% above control). The flow response curve was shifted to the right in the presence of H1 blocker, but the flow attenuation was overcome by the highest histamine dose. In contrast, the H2 blocker attenuated both epicardial dilation (6% below control) and flow response (31% above control) to the highest histamine dose. Results support a differential regulation of proximal epicardial and distal resistance vessels to histamine with epicardial arteries demonstrating H1-mediated vasoconstriction and H2-mediated vasodilation and distal resistance vessels showing H1- and H2-mediated vasodilation. In addition, these findings suggest that H1 blockade may antagonize histamine-related vasoconstriction and vasospasm, while H2 blockers may permit unopposed H1-mediated vasoconstriction of epicardial arteries and also limit resistance vessel vasodilatory responsiveness in the presence of elevated tissue histamine, as may occur in atherosclerotic coronary artery disease. PMID- 2892595 TI - Two dry-reagent systems evaluated for determinations of enzyme activities. AB - We evaluated the Kodak Ektachem DT60/DTSC and the Boehringer Mannheim Reflotron for measuring activity concentrations of six enzymes. The Ektachem CVs for low concentrations of aspartate aminotransferase and alanine aminotransferase were high. As compared with the Ektachem and a routine "wet-chemistry" system, values for aspartate aminotransferase and alanine aminotransferase were lower as measured by the Reflotron, because no pyridoxal 5'-phosphate is included in the Reflotron slides. Activity concentrations of gamma-glutamyltransferase and creatine kinase measured with the Ektachem and with the routine procedure did not agree well, possibly because the Ektachem gave too-high results for the enzyme activities. Assays of several commercial test sera indicated that test results by the dry-chemistry and routine procedures are not interconvertible. This contrasts with our previous experience, in which between-test agreement for several analytes was acceptable. PMID- 2892596 TI - International Federation of Clinical Chemistry: present and future. PMID- 2892598 TI - Elimination of heparin interference in the determination of gamma-GT. PMID- 2892597 TI - Chromatographic profiles of urinary isoenzymes in healthy children. AB - Urinary excretion of alkaline phosphatase, gamma-glutamyltransferase and lactate dehydrogenase was studied in a carefully selected group of 155 healthy children, 83 females and 72 males. Enzyme activity was assayed in randomly collected urine samples after gel filtration of the urine specimens. On chromatograms, urinary enzymes of alkaline phosphatase, gamma-glutamyltransferase and lactate dehydrogenase were separated into 4, 2 and 5 isoenzymes, respectively. Mean values of alkaline phosphatase, gamma-glutamyltransferase and lactate dehydrogenase activity were 4.59, 21.6 and 10.0 U/g creatinine. There were no sex related differences besides lactate dehydrogenase which showed a higher excretion in females than in males. The excretion of urinary enzymes clearly decreased with increasing age. PMID- 2892599 TI - Continuous subcutaneous pump infusion of somatostatin analogue SMS 201-995 versus subcutaneous injection schedule in acromegalic patients. AB - Diurnal serum GH patterns were determined in 10 acromegalic patients before treatment, after 3 d continuous s.c. pump infusion and then after 3 d with three equal daily s.c. injections in both instances totalling 100 micrograms/24 h. Subcutaneous injections (33 micrograms) induced impressive suppression of serum GH lasting 3-6 h in eight patients followed by escape to pretreatment values before the next injection. In contrast, continuous infusion resulted in greater and more stable 24 h suppression to the levels reached at the nadir between injections. Suppression of mean 24 h serum GH below 5 ng/ml was achieved by pump treatment in four patients, while two patients had mean values between 5 ng/ml and 10 ng/ml. In four patients occasional or all levels were above 10 ng/ml (24 h average 12.4-102 ng/ml) implying either that adequate suppression by the SMS 201 995, was impossible during the 3 d pump infusion period, or that the dose administered was inadequate. Carbohydrate tolerance was unaffected in either regimen, indicating that reduction in insulin antagonistic hormones balanced inhibition of insulin release. Interestingly, and in contrast to somatostatin, SMS 201-995 did not inhibit TSH release. No untoward effects were observed at the moderate dosage and blood clinical chemistry was unchanged. Fairly constant diurnal serum SMS 201-995 values were obtained during pump infusion, while levels undulated inversely with serum GH during injection treatment. Average diurnal serum somatostatin-C immunoreactivity (all patients) decreased from 496 +/- 129 (mean +/- SD) to 385 +/- 100 ng/ml (P less than 0.003) during pump treatment and did not decrease further during the following 3 d injection treatment (363 +/- 76 ng/ml). The normal adult mean is 179 +/- 40 ng/ml. Computer tomographic (CT) scans of the sellar region were performed in all patients before and after the experimental week. Two patients had extracellular tumours whose size decreased from 8.2 to 4.1 cm3 and from 12.6 to 10.5 cm3. The results demonstrate that superior and stable suppression of GH secretion is obtained during continuous s.c. pump infusion of SMS 201-995. PMID- 2892600 TI - The human NK cell--a short over-view and an hypothesis on NK recognition. PMID- 2892603 TI - Cutaneous uptake of gallium-67 in polyarteritis nodosa. PMID- 2892602 TI - Autoantibody to proliferating cell nuclear antigen (PCNA) in SLE: a clinical and serological study. AB - In a clinical and serological follow-up study on a large series of subjects with different connective tissue disorders, anti-PCNA/cyclin autoantibodies were found in about 3% of patients with SLE. Positive subjects showed a higher incidence of diffuse proliferative glomerulonephritis and hematological disorders than the general SLE population. A highly significant serological association between PCNA and SL/Ki autoantibodies (p less than 0.001) has been observed. Persistence or disappearance of serum PCNA antibodies were independent of any clinical and serological feature or the therapeutic regimen employed. PMID- 2892601 TI - Identification of gp108, a pathogenic antigen of passive Heymann nephritis, as dipeptidyl peptidase IV. AB - Our previous paper showed that the glycoprotein of Mr 108,000 (gp108) is one of the major components of rat renal tubular brush border antigens and that an injection of anti-gp108 antiserum in rats induces passive Heymann nephritis with acute and severe proteinuria. In this study, gp108 was identified as a monomer of dipeptidyl peptidase IV (DPP IV). The anti-gp108 antibody was shown to immunoprecipitate DPP IV from Triton-extract of renal tubular membrane fractions. DPP IV was co-purified with gp108 from the Triton-extract by columns of DEAE cellulose and Bio-gel A-1.5 m. The ratio of DPP IV activity and gp108 content was nearly constant throughout the purification steps. The final purified gp108 showed a high specific activity of DPP IV, comparable to that reported for purified rat DPP IV. These results indicate that gp108 is a monomer of DPP IV. PMID- 2892604 TI - Bacteremia with P-fimbriated Escherichia coli in diabetic patients: correlation between proteinuria and non-P-fimbriated strains. AB - In a consecutive material of 652 E. coli bacteremia 70 episodes (11%) were found in 64 patients with diabetes mellitus. 10 patients had insulin-dependent and 54 had non-insulin-dependent diabetes. The E. coli strains were tested for adhesive properties as mediated by P-fimbriae, a virulence factor in human urinary tract infections. Half of the strains were P-fimbriated with a higher occurrence in women (26/42, 62%) than in men (9/27, 33%). Diabetic patients with a positive urine culture had a higher incidence of P-fimbriated E. coli strains (27/37, 73%) in blood culture than patients with negative or no urine culture taken (8/32, 25%). Furthermore, patients without compromising factors, regardless of their diabetes mellitus, had a higher incidence of P-fimbriated E. coli strains (19/29, 66%) than those with malignancies and other debilitating diseases (6/22, 27%). The high incidence of P-fimbriated E. coli strains in the non-compromised patients may depend on the ability of such bacteria to invade the urinary tract and cause acute pyelonephritis, which often precedes E. coli bacteremia. A lower incidence of P-fimbriated E. coli strains was found in patients with proteinuria prior to the bacteremic episode (10/31, 32%), compared to those without proteinuria (25/35, 71%). No correlation was noted between P-fimbriation and duration of diabetes or serum creatinine. The low incidence of P-fimbriated E. coli strains in patients with proteinuria indicates that nephropathy, or some concurrent complication, predisposes the diabetic patient to bacteremia with low virulent, non-P-fimbriated E. coli. PMID- 2892605 TI - Influence of sodium concentration in cerebrospinal fluid on plasma atrial natriuretic peptide in conscious rats. AB - 1. To test the influence of a sodium (Na+) stimulus within the central nervous system on the release of atrial natriuretic peptide (ANP), we examined the effects of intracerebroventricular infusion of high Na+ artificial cerebrospinal fluid (CSF) on blood pressure, urinary Na+ excretion and plasma ANP levels in conscious Wistar rats. 2. Infusion of high Na+ (0.6 mol/l) CSF into the lateral ventricle at a rate of 1 microliter/min for 60 min significantly increased mean blood pressure and urinary Na+ excretion, while normal Na+ (0.15 mol/l) CSF had no effects. Plasma ANP levels were higher in the high Na+ CSF group than in the normal Na+ group (154 +/- 39 vs 52 +/- 19 pmol/l, P less than 0.05). 3. Interruption of the sympathetic nervous system and the vascular action of vasopressin with intravenous hexamethonium and d(CH2)5Tyr(Me)arginine vasopressin attenuated the pressor and natriuretic responses to intracerebroventricular high Na+ CSF. Plasma ANP levels in these rats did not differ significantly from those in rats which were similarly treated but were given normal Na+ CSF. 4. These results indicate that elevation of the CSF Na+ concentration without peripheral volume loading can stimulate ANP release into the circulation. ANP release due to central Na+ stimulus appears to be mediated by the sympathetic nervous system, vasopressin, and/or haemodynamic change caused by these factors. PMID- 2892606 TI - Choice of beta blockers in hypertensive patients who smoke. PMID- 2892608 TI - Susceptibility of Bordetella pertussis to five quinolone antimicrobic drugs. AB - Five quinolone antimicrobic agents were tested to determine the mean inhibitory concentration (MIC) of each of 17 clinical strains of Bordetella pertussis by the agar dilution method. Ciprofloxacin demonstrated the best in vitro activity with an MIC90 of 0.06 microgram/ml. Norfloxacin, ofloxacin and enoxacin were also highly active with MIC90s of 0.25, 0.25, and 0.5, respectively. Cinoxacin was only moderately active (MIC90 4.0 microgram/ml). PMID- 2892607 TI - A genetic analysis of type 2 (non-insulin-dependent) diabetes mellitus in Punjabi Sikhs and British Caucasoid patients. AB - A genetic analysis of diabetic and non-diabetic Punjabi Sikhs (n = 164) was made for markers of non-insulin-dependent diabetes mellitus using insulin receptor, insulin, and HLA-D alpha chain gene probes. Additionally British Caucasoids (n = 163) were studied using the insulin receptor probe. Insulin receptor gene restriction fragment length polymorphisms were defined using Southern blot techniques and the restriction enzyme Bgl II and BAm Hl. In Punjabi Sikhs and British Caucasoids neither of the restriction fragment length polymorphisms distinguished non-insulin-dependent diabetes mellitus subjects from controls. In the Sikhs no association with non-insulin-dependent diabetes mellitus was seen with the hypervariable region of the insulin gene or with HLA-DR/DQ/DX alpha chain restriction fragment length polymorphisms. We therefore conclude that despite the high prevalence of non-insulin-dependent diabetes mellitus in Asians we were unable to find any genetic markers for this disease using the available cloned gene probes. PMID- 2892609 TI - Nutritional status and energy metabolism of crayfish (Procambarus clarkii, Girard) muscle and hepatopancreas. AB - 1. Food deprivation resulted in significant decreases in muscle carbohydrate, lipid and water content and increased ATP, ADP, AMP and total adenylate levels over the 21-day experimental period. 2. In the hepatopancreas phosphoarginine was significantly higher on day 21 in the starved crayfish. 3. Muscle energy charges remained within optimal (unstressed) ranges, while hepatopancreatic energy charges of food-deprived crayfish fell into suboptimal (stressed) ranges, indicating the necessity of examining organs separately to accurately ascertain metabolic changes in response to stressors. PMID- 2892610 TI - Liver glycogen and plasma insulin and glucagon levels in food- and water-deprived black-tailed prairie dogs (Cynomys ludovicianus). AB - 1. Liver glycogen levels and plasma levels of insulin and glucagon were measured in fed and in food- and water-deprived prairie dogs. 2. Liver glycogen values decreased from 45.5 to 12.4 mg/g (73%) after 21 days of food and water deprivation, while a 24-hr fast resulted in a liver glycogen value of 47.5 mg/g. 3. Rat liver glycogen values decreased from 45.6 to 2.3 mg/g (95%) after a 24-hr fast. 4. Prairie dog plasma insulin values were 69.2, 15.8 and 25.4 microU/ml in fed, and in 24-hr and 32-day food- and water-deprived animals, respectively. 5. Prairie dog plasma glucagon levels were 57.0 and 38.4 microU/ml in fed and in 32 day food- and water-deprived animals. 6. Plasma values for glucose, urea nitrogen, acetone and triglyceride agreed with previously published results. 7. We conclude that it is possible that the maintenance of liver glycogen levels in food- and water-deprived prairie dogs may be correlated with a smaller decrease in plasma insulin levels, relative to other species, and with a decrease in plasma glucagon levels. PMID- 2892611 TI - Origins of peripheral and brainstem auditory responses in the White Leghorn chick. AB - 1. Peripheral and central auditory projections were sectioned and far-field recordings measured to determine neural generators of the waveform in the White Leghorn chick. 2. The mesencephalicus lateralis p. dorsalis and more rostral structures do not contribute to the waveform. 3. Activity of N.VIII is reflected in peaks P1A and P2A; N2A appears to be central in origin but may be in part from the central stump of N.VIII. 4. The crossed dorsal cochlear tract but not the trapezoid body is necessary for P3A and P4A; it is therefore functionally homologous to mammalian trapezoid fibres. 5. P1A, P2A, N2A, P2B are not dependent on crossing fibres. PMID- 2892612 TI - Effect of theophylline on ion transport in the lizard colon. AB - 1. The effect of theophylline on ion transport was examined using an in vitro short-circuited preparation of lizard colon. 2. Theophylline increased short circuit current (Isc) and transmural potential difference (PD). This increase caused by theophylline was accompanied by a small increase in transmural conductance (Gt). 3. Theophylline did not inhibit the absorption of Na+ but reversed Cl- absorption to secretion. This latter effect was due to an increase of the serosal-to-mucosal flux of Cl-. 4. Ion substitution experiments revealed that the effect of theophylline was Na+- and HCO3(-)-dependent and that these ions were required in the bathing solution. 5. These results with lizard colon are compared with those reported for mammalian colon and the mechanism of theophylline-induced Cl- secretion in these epithelia is discussed. PMID- 2892613 TI - Intestinal glucose and galactose transport in the cultured gilthead bream (Sparus aurata). AB - 1. Electrical parameters and transepithelial glucose and galactose transport were determined in vitro across anterior and posterior intestine of the culture fish Sparus aurata. 2. Electrical potential difference (PD) and short-circuit current (Isc) were serosa-positive in anterior intestine, while they were serosa-negative or near zero in posterior intestine. 3. Tissue conductance (Gt) was higher in posterior than in anterior intestine. In both parts it was decreased when the Na ion was omitted in mucosal and serosal reservoirs. 4. Addition of glucose or galactose to the mucosal side of intestine caused an increase in PD and Isc in posterior intestine but did not significantly change PD and Isc in anterior intestine. 5. Isotopic flux of glucose and galactose measurements in short circuit conditions showed a net active glucose and galactose absorption in posterior intestine, while in anterior intestine active transport of glucose or galactose was not observed. 6. The net transport of glucose and galactose in posterior intestine was decreased to zero in the absence of Na in mucosal and serosal reservoirs or in the presence of ouabain (1 mM) in serosal solution. PMID- 2892614 TI - Respiration of antarctic fish from McMurdo Sound. AB - 1. Resting rates of oxygen uptake were measured for nine species of unstressed fish living at -1.8 degree C in McMurdo Sound, Antarctica (77-78 degrees S). Interspecific differences in VO2 were correlated with the habits and activity of the fish. 2. The cryopelagic Pagothenia borchgrevinki regulated oxygen uptake down to a critical PO2 of approximately 60 mmHg. The inactive benthic species Trematomus centronotus extracted oxygen to lower PO2 and appeared to have a lesser degree of oxyregulation when the data were analysed using a quadratic model. 3. Cutaneous oxygen uptake in the nototheniids T. bernacchii and P. borchgrevinki amounted to 9 and 17% of total VO2 under normoxic conditions which is less than that reported for scaleless Antarctic fish. 4. The contentious concept of metabolic cold adaptation in polar fish has been reviewed, and the opinion expressed that the phenomenon cannot be dismissed on the grounds of technically incompetent measurement, or through inappropriate extrapolation of data from fish at lower latitudes. PMID- 2892615 TI - Cold-acclimation improves cold-tolerance of diabetic rats. AB - 1. The aim of these experiments was to study the extent to which previous cold acclimation improves the cold-tolerance of diabetic rats. 2. Alloxan diabetic rats (fasting blood glucose higher than 200 mg/dl) were used in the experiments. 3. In Expt. 1, non-cold-acclimated control and diabetic rats were exposed to cold environment (7-9 degrees C), and the percentage of survival calculated during a 12-day experimental period. In Expt. 2, the rats were previously cold-acclimated before alloxan or saline injection (diabetic and control cold-acclimated rats) and the survival rate was also assessed during a 12-day period in the cold. 4. The percentage of survival of the non-cold-acclimated diabetic rats (Expt.1) was 19% compared with 79% of the diabetic cold-acclimated animals (Expt. 2). There were no deaths in the control groups. 5. Cold-acclimated diabetic rats maintained a near-normal thermogenic response after noradrenaline injection. This response was impaired in non-cold-acclimated diabetic rats. 6. The results of these experiments suggest that the enhanced cold-tolerance of diabetic cold-acclimated rats could be related to the increased sympathetic activity and enhanced insulin sensitivity in thermogenic tissues, such as brown fat. PMID- 2892616 TI - Na+ transport in perfused intestine and in isolated enterocytes of freshwater trout deprived of essential fatty acid. AB - 1. Unidirectional Na+ fluxes obtained in perfused preparation of intestine and Na+ effluxes from enterocytes isolated by a specific method have been determined in the middle intestine of freshwater rainbow trout. 2. Fish were fed semi purified diets containing 8% by wt of either cod liver oil as reference, grape seed oil or hydrogenated coconut oil which are both deficient in fatty acids (FA) of the (n-3) series essential for the trout. 3. Important modifications in the Na+ intestinal absorption were induced by these deficient diets when measured in perfused intestine. 4. Conversely, no changes were seen in the Na+ active or passive effluxed when measured in enterocytes isolated from trout fed the same diets. 5. Na+,K+-ATPase activities were also unmodified by any diet. 6. It is concluded that deprivation of essential fatty acids reduces Na+ absorption capabilities of trout intestine, an effect which is mainly located at the apical membrane of enterocytes. 7. These results strongly demonstrate that apical entry and active serosal transport are separately modified in trout intestine by EFA deficient diet. 8. Furthermore the FA of the (n-3) series are essential for the retention of functional properties of membranes and ionic permeabilities in particular. PMID- 2892618 TI - The distribution and turnover of 35S methionine as influenced by diet in the dark eyed Junco (Junco hyemalis). AB - 1. Dark-eyed Juncos (Junco hyemalis) were maintained on one of three semi synthetic diets, differing only in their sulphur amino acid content. 2. 35S methionine was administered intraperitoneally after 3 days on their respective diets and the animals were killed 24 or 96 hr post-injection. 3. Faecal loss of 35S-methionine was significantly lower in the low methionine/high cysteine (HC) group after 24 hr when compared with other two dietary groups (4.69 vs 5.53 and 5.47%) indicating a whole-body conservation of the limiting amino acid. 4. Incorporation of 35S-methionine in hepatic and intestinal tissues was also greater in the HC group, even as the animals were losing body weight. PMID- 2892617 TI - Transient changes of the intestinal absorption of sodium and chloride in the rainbow trout after abrupt transfer into sea-water. AB - 1. Unidirectional fluxes of Na+ and Cl-, ouabain-sensitive Na+,K+-ATPase activity and the protein content have been determined in the intestine of trout in fresh water (FW) and 1, 2, 7 days after sea-water (SW) transfer. 2. After abrupt transfer in SW the Na+ and Cl- transports follow in two phases: first, a permeabilization of the epithelium during the first day; secondly, a transient impermeabilization and increase of the protein content of the mucosa (2 days after SW transfer) and a progressive increase of both the unidirectional Na+, Cl- fluxes and the Na+,K+-ATPase activity (7 days after SW transfer). 3. After 7 days SW the adaptation of the enterocytes which is different for Na+ and Cl- and for the middle and the posterior intestine is not achieved. PMID- 2892619 TI - Hematological data and hemoglobin components in bats (Vespertilionidae). AB - 1. Statistically significant variations were observed in the RBC counts and Hb concentration in pregnant females of Pipistrellus pipistrellus. 2. Basic hematological values in 59 animals of five species of insectivorous bats were estimated. 3. Electrophoretic separation of the hemoglobins of Plecotus austriacus, Myotis nattereri and Myotis myotis showed two components, whereas in Miniopterus schreibersi and Pipistrellus pipistrellus appeared three and four components, respectively. PMID- 2892620 TI - Basic haematological values in the Cameroon goat (Capra hircus). AB - 1. Basic haematological values in 165 Cameroon goats (Capra hircus) are reported. 2. The erythrocyte count, mean 14.36 x 10(12) l-1, ranged from 8.24 to 24.7 x 10(12) l-1; the haematocrit values, mean 0.304, varied from 0.20 to 0.38; the haemoglobin content, mean 113.4 g/l, was in the range from 83.0 to 143.0 g/l and the leukocyte count, mean 13.67 x 10(9) l-1, had lowest and highest values between 5.4 and 24.5 x 10(9) l-1. 3. Comparing these blood constituents in 47 male and 118 female Cameroon goats we demonstrated statistically significant lower values of the haematocrit and haemoglobin content and a statistically significant higher proportion of lymphocytes in the female animals. 4. In 16 pregnant and 30 non-pregnant female Cameroon goats, all animals older than 3 years, no statistically significant differences of the red blood picture were noted. 5. Also in three groups, assorted according to age, no significant changes in basic haematological parameters were seen. 6. During one year follow-up of some haematological parameters, statistically significant seasonal changes were found. 7. All presented data are compared with values abstracted from the literature and discussed. PMID- 2892621 TI - Effect of high hydrostatic pressure on 86Rb+ influx in the erythrocyte of the plaice (Pleuronectes platessa). AB - 1. 86Rb+ influx in the erythrocyte of the plaice (Pleuronectes platessa) has been measured at hydrostatic pressures between 1 and 600 atm at 10 degrees C. 2. The measurements were performed with an experimental medium containing 1% (w/v) bovine serum albumin. In this medium the cells achieved a steady state level of ionic regulation. 3. At normal atmospheric pressure 46% of the 86Rb+ influx was inhibited by furosemide while 42% was inhibited by ouabain, the remainder being inhibited by neither drug. 4. It was found that all three fluxes defined by these drugs were sensitive to pressure. 5. The ouabain sensitive influx was progressively inhibited by increasing pressure, the inhibition at 600 atm being 30%. 6. The furosemide sensitive influx was inhibited by 35% between 100 and 600 atm. 7. In contrast the ouabain + furosemide insensitive influx was doubled by 400 atm. 8. This pattern of pressure inhibition and stimulation resembles that seen in comparable studies in human erythrocytes. PMID- 2892623 TI - Protein requirements of subadult nilgai antelope. AB - 1. The maintenance crude protein (CP) requirements of subadult nilgai antelope (Boselaphus tragocamelus) were determined by nitrogen balance. Four isocaloric pelleted diets, ranging from 8.4 to 23.8% CP, were fed. 2. Subadults maintained a positive nitrogen balance on all diets. Linear regression showed that 95.8% of diet CP was truly digested and estimated metabolic fecal nitrogen (NFN) excretion at 0.388 gN/W0.75/day. 3. Estimates for endogenous urinary nitrogen excretion and maintenance nitrogen requirement, derived through linear regression, were erroneous. Consequently, the former was calculated based on metabolic size (0.126 gN/W0.75/day) and added to MFN to obtain an 0.514 gN/W0.75/day estimate of required nitrogen for maintenance. This value is between the levels recommended for maintenance of yearling deer and cattle. 4. Given the same level of dry matter intake (68.6 g/W0.75/day) and true CP digestibility, study animals would be able to meet N equilibrium on a 4.89% CP (dry matter basis) diet. 5. Based on data from other sources, natural diets containing 6.98% CP would need to be consumed by free-ranging subadults to maintain body weight. PMID- 2892624 TI - The effect of oral l-carnitine on lipoprotein composition in the Watanabe Heritable Hyperlipidemic Rabbit (Oryctolagus cuniculus). AB - 1. We have recently reported the ability of orally administered l-carnitine to lower plasma triglyceride in the Watanabe Heritable Hyperlipidemic Rabbit (WHHL), an animal model of familial hyperlipoproteinemia. 2. In the present studies we examined the effect of l-carnitine administration upon individual lipoprotein subfractions in this animal model. 3. Carnitine feeding resulted in a reduction in very low density lipoproteins (VLDL) and high density lipoprotein (HDL). 4. Compositional analysis revealed a reduction in core triglyceride content with a concomitant increase in protein and phospholipid in VLDL and low density lipoproteins (LDL). 5. Conversely, electrophoretic mobility and apolipoprotein composition were unchanged with l-carnitine. 6. These results further demonstrate the ability of l-carnitine to modulate lipoprotein lipid composition in this animal model of familial hyperlipoproteinemia. PMID- 2892622 TI - Cation dependence of frog gustatory neural responses to acid stimuli. AB - 1. To understand the mechanism underlying the gustatory response for acid stimuli, the characteristics of glossopharyngeal neural responses elicited by 1 mM hydrochloric acid (HCl) in bullfrogs were examined by changing the ionic composition of adapting solutions flowed on the tongue surface. 2. The amplitude of the gustatory neural response for HCl was increased with an increase of Ca2+ concentration in the adapting solution. 3. The action of Ca2+ in the adapting solution could be replaced by Ba2+ and Sr2+, and was inhibited by Co2+, suggesting that the Ca2+ channel in the receptor membrane of taste cells is related to a gustatory neural response to acid. PMID- 2892625 TI - The time-course of appearance and net accumulation of horseradish peroxidase (HRP) presented orally to rainbow trout Salmo gairdneri (Richardson). AB - 1. A sensitive enzyme-linked immunosorbent assay (ELISA) technique was used in order to determine horseradish peroxidase (HRP) uptake from the rainbow trout gut. 2. HRP was detected in blood plasma and various tissues within 15 min of oral intubation. 3. The time-course of net accumulation (uptake-degradation) over a 75 min period was recorded. 4. The presence of HRP reached a maximum in the body tissues approximately 45 min after intubation and on a ng/g weight basis the order of accumulation within the tissues was liver greater than spleen = kidney greater than plasma greater than heart. 5. The total organ accumulation (net) was in the order liver greater than plasma greater than kidney greater than spleen greater than heart. PMID- 2892626 TI - Isolation and characterization of brush border membrane vesicles from pig small intestine. AB - 1. Brush border membrane vesicles (BBMV) were isolated from swine mid-intestine by a MgCl2 precipitation and sucrose density gradient centrifugation. 2. Transport of D-glucose and L-alanine were Na+-stimulated and into an osmotically sensitive space. 3. Estimates of kinetic parameters for Na+-dependent D-glucose transport were: apparent Kt = 1.8 mM and Jmax = 16.8 nmol/mg protein/min. 4. Results of experiments with the delta pH sensitive fluorescent probe 9 aminoacridine indicated independent mechanisms for Na+-dependent glucose transport and Na+/H+ exchange. 5. This study demonstrates that pig BBMV provide a useful model for investigating intestinal membrane transport. PMID- 2892627 TI - Bacterial endotoxin and infection cause behavioural hypothermia in infant mice. AB - 1. When placed in a temperature gradient, 3-10 day old mice injected with living Escherichia coli or with E. coli endotoxin, select 2-3 degrees C lower temperatures than their litter-mate controls injected with saline. 2. At the lower selected temperature (32 degrees C) young mouse pups resist bacterial infection for longer and tolerate higher doses of endotoxin than at the temperature selected by the controls (35 degrees C). 3. It is possible that a controlled hypothermic state, here called cryexia, is in small mammals an alternative strategy to fever for coping with infections. PMID- 2892628 TI - Reference standards and the physiologic significance of the pregnant goat (Capra hircus) as a human model in obstetrical research. AB - 1. Amniotic fluid, cerebrospinal fluid, serum, and urine chemistries; respiratory rate and arterial and mixed venous blood gases; heart rate, hematocrit, and cardiac output; and arterial, pulmonary artery, central venous and pulmonary wedge pressures were measured in 20 pregnant adult goats of 19.5-34 kg body weight. 2. Arithmetic means, standard deviations, and coefficients of variation were calculated to develop reference values; in addition, the 95% confidence limits for ranges were established. 3. Comparison of derived data with that from non-pregnant goats shows changes similar to those seen when examining pregnant and non-pregnant humans. 4. These results indicate the pregnant goat is an acceptable model for human obstetrical research. PMID- 2892629 TI - Effect of osmolality on the initiation of sperm motility in Xenopus laevis. AB - 1. Seminal plasma of the South African clawed toad Xenopus laevis exhibited osmolality around 250 mosmol/kg isotonic to blood plasma. 2. Spermatozoa remained immotile when the semen was diluted in solutions of 100 mM NaCl, 100 mM KCl or 200 mM glucose containing 20 mM Hepes-NaOH buffer which exhibited almost the same osmolalities (approximately 240 mosmol/kg) as seminal plasma. 3. The spermatozoa became motile in these three solutions if the osmolalities were decreased. 4. These suggest that motility of Xenopus sperm is suppressed by seminal osmolality in the reproductive organ and initiated by a decrease of osmolality when they are spawned into hypotonic fresh water. PMID- 2892630 TI - Effects of hydrostatic pressure on the motor activity of fish from shallow water and 900 m depths; some results of Challenger cruise 6B/85. AB - 1. Two species of benthic fish from 900 m depths (90 atm pressure), Trachyscorpia cristulata echinata and Synaphobranchus kaupi, are shown to be adapted to their normal, high ambient pressure. 2. Their condition improves when they are restored to their normal pressure after experiencing decompression in a trawl and they undergo convulsions at 150 atm. 3. This contrasts with the response of shallow water species (Salmo salar, Pleuronectes platessa, Anguilla anguilla and Gadus morhua) which convulse at 93-114 atm and become immobilized and rigid at 150 atm. PMID- 2892631 TI - Hematologic and coagulation studies on cotton rats, Sigmodon hispidus. AB - 1. Blood coagulation factor levels and the normal ranges of commonly used coagulation tests were established for Sigmodon hispidus. 2. The white cell, red cell and platelet counts have been determined together with the red cell parameters as measured by the Coulter model S-plus. 3. The relationship between the results reported here and those published for related species are discussed. PMID- 2892632 TI - Short-term changes in natripheric and hydrosmotic water fluxes across the skin and in urine production due to increases in the osmolarity of the external environment in the toad. AB - 1. Sudden decreases in the osmotic gradient across the skin due to the replacement of water of the bath by 115 mM NaCl had no effect on water uptake of intact or hypophysectomized toads. 2. A concomitant decrease in the urine production was observed in intact but not in hypophysectomized animals. 3. Addition of amiloride chlorydrate (0.25 mM) to the 115 mM NaCl bath induced a significant decrease in water uptake both in intact and in hypophysectomized toads. 4. The osmotic permeability coefficient (LPD) increased significantly during the osmotic gradient reduction with 115 mM NaCl plus 0.25 mM amiloride or 230 mM sucrose in both groups. 5. No changes in the plasmatic osmolarity were detected during the development of these responses to the osmotic gradient reduction. 6. These results are consistent with the hypothesis of short-term changes in the natripheric and hydrosmotic fluxes of water across the skin and in urine production triggered by the osmotic gradient reduction. The possible participation of arginine vasotocin in these responses is discussed. PMID- 2892633 TI - Blood serum chemistry measurements of normal and acutely stressed channel catfish. AB - 1. An automated blood serum chemistry analytical system designed for human usage was employed to establish the levels of 26 different components present in sera obtained from various experimental groups of channel catfish. 2. Comparisons of samples from feral and commercial production pond fish during warm months indicated statistically significant differences in the serum levels of sodium, CO2, urea nitrogen, direct bilirubin, cholesterol, creatinine and protein. 3. Laboratory acclimated and production pond fish exhibited differences in serum electrolytes (sodium, potassium, chloride, phosphorus), serum metabolites (urea nitrogen, creatinine, triglycerides), serum enzymes [gamma-glutamyl transferase, glutamate-oxaloacetate transaminase (GOT), lactate dehydrogenase (LDH), alkaline phosphatase, and amylase], and serum iron. 4. Seasonal (temperature?) differences in production pond fish were noted for 12 serum components including potassium, magnesium, CO2, glucose, creatinine, albumin, iron, alkaline phosphatase, and glutamate-pyruvate transaminase (GPT). 5. Comparisons of samples obtained from laboratory-acclimated fish before and 18 hours after acute handling and transport stress revealed significant differences in only three serum parameters: glucose, LDH, and creatine phosphokinase (CPK). 6. These studies suggest that "normal" values established by any method of sera analysis may be different in the same species depending on the diet, season, and presence of environmental stressors. PMID- 2892634 TI - The effect of pressure on the lateral swimming muscle of the European eel Anguilla anguilla and the deep sea eel Histiobranchus bathybius; results of Challenger cruise 6B/85. AB - 1. The viability of Histiobranchus lateral muscle was prolonged up to 7 times by recompression of the tissue. 2. The maximum twitch contraction force of both Anguilla and Histiobranchus was recorded at a pressure between 150 and 350 atm. At 1 atm Anguilla developed 60% maximum force and Histiobranchus 10-20% maximum force. 3. Twitch contraction time doubled for a pressure increase of 400 atm. This effect is predicted to halve the maximum swimming speed at 4000 m and is discussed in relation to muscle force and anaerobic support. PMID- 2892635 TI - Blood oxygen equilibria and theoretical models. I. Effect of protons in trout (Salmo gairdneri) and human red cells, in absence of organic phosphates. AB - 1. Oxygen equilibrium curves were measured on red cells that had been depleted of organic phosphates, for rainbow trout red cells between pH 7-9, at 15 and 20 degrees C, and for human red cells between pH 6.8-8.0, at 37 degrees C. 2. The data were fitted to the models of Adair and of Monod et al. (MWC model). Parameters were estimated by the non-linear least-squares method, from which the number of Bohr protons released during oxygenation was calculated. 3. For trout as for human red cells, the pH affects the first step of oxygenation and the overall oxygenation in nearly equal proportion. For human red cells, the association constant for binding of the last oxygen, expressed by k4 or kR, is not affected by pH, indicating that the R structure is free of constraints. For trout red cells, there is a pronounced pH dependence of this constant at low pH, which is about 10-fold increased between pH 7-9. This corresponds to the Root effect that impairs the T----R transition, and confirms previously published data for normal trout and human red cells. 4. For trout red cells, small functional heterogeneity is evidenced, despite Hb multiplicity, and effect seems linked to the level of temperature. 5. The specific effect of organic phosphates, evident for human red cells, contrasts with a lack of effect for trout red cells, when taking into account the intracellular pH values. PMID- 2892637 TI - Photoreceptor evoked potentials and phototactic behaviour in Cercaria caribbea LXXI cable. AB - 1. Transient potential changes evoked in response to light stimuli, and presumably arising from rhabdomeric eye-spots in the cercarial body, were recorded for the first time, to our knowledge, in helminth parasites. 2. Pigmented Cercaria caribbea LXXI gave a very slowly adapting response to maintained light stimulus, while a non-pigmented variety appeared to emit a stronger, rapidly adapting response to light onset. 3. Swimming towards a directional light source is disrupted by several neuropharmacological agents, which presumably disturb synaptic transmission in the nerve/muscle system. 4. The light evoked potentials were unaffected by these same agents and therefore, appeared to be directly recorded receptor potentials. PMID- 2892636 TI - Blood oxygen equilibria and theoretical models. II. A critical estimation. AB - 1. Theoretical models can fit the oxygen equilibria of trout and human red cell suspensions, and describe the apparent oxygenation process in the red cell. 2. The assumption that full oxygenation is attained at atmospheric O2 pressures can result in biphasic Hill plots and high Hill coefficients for high O2 saturations. This phenomenon must not be confused with aggregation of hemoglobin. 3. Problems specific to measurements of red cell suspensions, regarding the ionic cellular composition and its stability with time, are approached. Changes of buffer osmolarity, and--for trout--addition of adrenaline, within physiological proportions, have no impact on the results. 4. This tends to validate the general significance of equilibrium data obtained on this material, regarding the effects of protons and organic phosphates, although complex ionic movements across the red cell membrane are known to occur in the animal under certain circumstances. PMID- 2892638 TI - Distribution of contractile proteins in single isolated smooth muscle cells from the ascidian body-wall muscle. AB - 1. Relaxed cells isolated from ascidian body-wall muscle were morphologically very similar to relaxed common smooth muscle cells. 2. The contracted cells, however, possessed striations which were resolved into a repeating pattern of light and dark bands using phase contrast microscope. 3. The relaxed ascidian cells treated with Triton X-100 were contracted and showed the striations by adding Ca2+. 4. By an indirect immunofluorescence method, it was clearly seen that antiactin spread uniformly in the relaxed cells, while this antibody was concentrated on the dark bands of striations in the contracted cells. PMID- 2892639 TI - Hematology of the hibernating bat: Myotis daubentoni. AB - 1. Hematological parameters in the male and female bats differ only with respect to number and volume of erythrocytes: larger number of smaller cells found in males corresponds to smaller number of larger red blood cells in females, with hemoglobin level and hematocrit values remaining similar in both sexes. 2. Six month-old bats have significantly higher numbers of lymphocytes when compared with adults. 3. There are no significant differences in hemograms (complete blood counts) for bats identified as "nathalinae" and "typical" Myotis daubentoni. PMID- 2892640 TI - Sensory responses and axonal morphology of two different types of cerebral neurones in Helix pomatia L. AB - 1. The mechano- and chemosensory responses of two different types of cerebral neurones responding to food stimuli were studied by microelectrophysiological techniques. This was correlated with axonal morphology investigated by intracellular Co-lysine labelling. 2. The C4 neurone responded to food stimuli applied to the lip receptors by phasic (less than 30 sec duration), while the C14 neurone by an initial phasic and a subsequent tonic longer than 10 min duration) activity change. 3. The different sensory responses of the two neurones can partly be explained by the morphological differences found between them. PMID- 2892641 TI - Blood levels of thyroid hormones and certain metabolites in relation to moult in the harp seal (Phoca groenlandica). AB - 1. Changes in blood levels of thyroxine (T4), triiodothyronine (T3), free fatty acids (FFA), glucose, pyruvic acid and lactic acid in the harp seal during moult, were studied. 2. Serum levels of both T4 and T3 showed significant increase in the moult phase from that in the pre-moult phase. While T4 level continued to remain high during the early and late post-moult phases, T3 level dropped in the latter two phases to the same low pre-moult level. 3. The T3/T4 ratio was significantly higher during the pre-moult phase than that in all the other phases. It is suggested that the high pre-moult T3/T4 ratio marks the initiation of moult. 4. There were no significant changes in the levels of the metabolites studied except that of FFA which was highest in the moult phase indicating the hormonal basis of lipid mobilization. PMID- 2892642 TI - Energy and water requirements of lactation in the North American porcupine, Erethizon dorsatum. AB - 1. Energy and water requirements of lactating porcupines were compared with results of previous studies on energetics of reproduction in small-bodied rodents. 2. Mass-specific food and water intake of control and lactating porcupines was examined throughout the 68-78 days of lactation. Water intake of lactating females was 16% higher than that of non-lactating animals. 3. Digestive efficiency of porcupines fed commercial rabbit chow was 54-60%; there was no significant difference in efficiency between lactating and non-lactating animals. 4. Total mean energetic intake throughout lactation was only 17% greater than that of non-lactating animals. 5. Reproductive rate and costs of lactation in porcupines are considerably less than in other rodents and other comparably-sized mammals, but the amount of energy allocated to each offspring is quite high. 6. The reproductive pattern of porcupines is associated with low juvenile mortality and long adult lifespan (both of which reflect the porcupine's protective morphology), and may be related to the quality of winter diets. PMID- 2892643 TI - Plasma immunoreactive calcitonin in the frog (Rana pipiens). AB - 1. Plasma immunoreactive calcitonin (iCT) and ionic calcium [( Ca]i) were measured in intact frogs (Rana pipiens) within complete 24 hr light-dark cycles over an 18 month period. 2. Plasma iCT exhibits an annual periodicity about the annual mean of 10.0 ng/ml, with an amplitude of 5.4 ng/ml that peaks in October. 3. Within an annual cycle, a significant inverse association exists between the basal monthly levels of plasma iCT and [Ca]i for animals maintained in freshwater control conditions. 4. When subjected to a high calcium environment during the latter half of the year, plasma [Ca]i and iCT were elevated above control levels but exhibited independent cyclic patterns. 5. A distinct seasonal response of increased iCT in a high calcium environment may be related to the secretory activity of the ultimobranchial glands and physiological responsiveness to other calcemic hormones; e.g. parathyroid hormone and vitamin D. PMID- 2892644 TI - Ionic current of an identifiable giant neurone, d-RPLN, of an African giant snail (Achatina fulica Ferussac), measured under voltage clamping--II. Outward currents. AB - 1. The outward currents of d-RPLN (dorsal-right parietal large neurone), one of the largest identifiable neurones of an African giant snail, were studied. 2. At the holding potential (-90 mV) and at the command voltage (Vc20 mV), the current values were 3.05 +/- 0.13 microA (M +/- SE) for the peak (n = 38), and 1.96 +/- 0.10 microA for the plateau (n = 37). 3. The peak time constant (Vc = 0 mV) was 2.05 +/- 0.08 msec. 4. Tetraethylammonium at 50 mM reduced the plateau value up to 50-55% of the normal, but had little effect on the peak. 5. 5-Aminopyridine at 5.0 mM diminished the peak value to about 50-55%, and delayed the peak time. 6. Quinine at 0.25 mM decreased both the peak and the plateau approximately to 55 65% of their controls, but shortened the peak time when Vc was beyond 0 mV, in contrast to the case of 4-AP. 7. The calcium-free state (replaced with cobalt) reduced these currents to about 75% of the normal, and evidently delayed the peak time. PMID- 2892645 TI - Stimulation of anaerobic metabolism in rats at high altitude hypoxia--adrenergic effects dependent on dietary states. AB - 1. Plasma lactate and pyruvate were increased more markedly in fed rats than in fasted rats exposed to an 8000 m altitude. 2. The increase in plasma lactate and pyruvate was enhanced and inhibited by the alpha 1-adrenergic antagonist prazosin and the beta-blocker propranolol, respectively, in fasted rats exposed to an 8000 m altitude. Blood glucose was not changed by adrenergic blockades under the same conditions. 3. Prazosin and propranolol showed no effect on glycolytic metabolites in plasma in fed rats submitted to an 8000 m altitude. Blood glucose of fed rats was increased by alpha 1-blockade during severe hypoxia. 4. In fasted rats whose energy metabolism depends on oxidation mainly, alpha 1- and beta adrenergic receptors can participate in the stimulation of respiration and the glycogen degradation, respectively, during an exposure to severe hypoxia. In fed rats energy metabolism depends on glycolysis, which utilizes blood glucose as the substrate preferentially during hypoxia. PMID- 2892647 TI - Managing critically ill patients with esmolol. An ultra short-acting beta adrenergic blocker. AB - Esmolol is a new intravenous beta-adrenergic blocker with an ultrashort (nine minute) elimination half-life, which has been studied predominantly for control of supraventricular tachycardia and management of certain types of hypertension. Clinical studies indicate that the efficacy of esmolol is equivalent to that of propranolol and verapamil for control of supraventricular tachycardia and to sodium nitroferricyanide (sodium nitroprusside) for control of postoperative hypertension. Esmolol also has been shown to control heart rate and blood pressure during episodes of acute myocardial ischemia. Cardioselectivity is similar to that of metoprolol, and the ability to titrate the effect of esmolol may provide additional assurance that beta-adrenergic blockade will remain within the cardioselective range. The most commonly observed adverse effect seen in clinical trials was asymptomatic hypotension. Hypotension may be minimized by titrating to the minimum effective dose and is readily reversed within 10 to 30 minutes of discontinuing the infusion of esmolol. These unique features represent advantages of great potential merit in critical care medicine. PMID- 2892646 TI - Paralysis and sedation. PMID- 2892648 TI - [Clinicopathologic study of polyarteritis nodosa. Report of 5 autopsied cases]. PMID- 2892649 TI - [Clinical significance of changes in the beta 2-microglobulin values of serum and urine in patients with epidemic hemorrhagic fever]. PMID- 2892650 TI - [Combined antiallergic therapy in the treatment of epidemic hemorrhagic fever]. PMID- 2892651 TI - [Dynamic changes in the creatinine clearance rate in different types of epidemic hemorrhage fever]. PMID- 2892652 TI - [Detection of viral antigens in various organs in 14 fatal cases of epidemic hemorrhagic fever]. PMID- 2892653 TI - [Advances in the diagnosis of epidemic hemorrhagic fever]. PMID- 2892654 TI - Sulfasalazine-induced abnormal sperm penetration assay reversed on changing to 5 aminosalicylic acid enemas. AB - Sulfasalazine, a drug used in the treatment of inflammatory bowel disease, has been associated with male infertility, an effect attributed to sulfapyridine rather than to 5-aminosalicylic acid (5-ASA), the presumed therapeutically active component of sulfasalazine. Recently, the sperm penetration assay (SPA) has been found to be an accurate method of quantitating male fertilization potential. We report the case of a man with ulcerative colitis in whom infertility and a markedly abnormal SPA were demonstrated while he was taking sulfasalazine. Shortly after discontinuing sulfasalazine and initiating treatment with 5-ASA enemas, his SPA became normal and his wife became pregnant. The SPA is a useful screening test for sulfasalazine-induced male infertility. On the other hand, 5 ASA enemas do not appear to be associated with an abnormal SPA. PMID- 2892655 TI - Fine-needle aspiration biopsy in the diagnosis of metastases in the liver. AB - During the years 1975-1985, fine-needle aspiration biopsy of the liver was performed in 655 patients. The procedure entailed no complications. In 302 (46%) cases, the samples contained malignant cells; in 238 (36%), liver cells; in 46 (7%), cells suspected of malignancy; in 69 (11%) of cases, the samples were unsatisfactory. The medical records of 242 patients were reviewed. Based on the results of different examinations it was established that 149 patients had liver metastases and 62 did not. In 31 patients, evaluation could not be done owing to insufficient data. The cytological findings were compared with the results of liver scintiscan, Alcaline phosphatase, serum gamma-glutamyltranspeptidase, and histological diagnoses. There were no false-positive cytological diagnoses. False negative diagnoses were found in 14% of cases. Cytologically positive samples from known primaries were reviewed. It has been established that pallisade-like formations are characteristic for metastases of intestinal carcinoma; usually in these cases, necrotic material and inflammatory cells were found as well. PMID- 2892656 TI - Effects of beta-agonists on b- and c-waves implicit for adrenergic mechanisms in cat retina. AB - Nylidrin (buphenine) is a beta-adrenergic agonist known to dilate peripheral vessels and used therapeutically in retinal degeneration and glaucoma. We studied retinal function under beta-agonists in arterially perfused cat eyes and observed a dose-dependent, reversible increase in b-wave amplitude and a decrease in c wave amplitude in concentrations from 4.5 to 120 microM. A half maximal response was obtained at 40 to 50 microM. The optic nerve response to light showed dose dependent reversible changes under nylidrin. Standing potential, light peak, intraocular pressure, vascular resistance, and diameter of or retinal vessels showed no consistent changes under nylidrin. The effect were inhibited by each of the beta-blocking agents propranolol, ICI 118, and oxprenolol (in sequence of decreasing potency). Another potent beta 2-agonist, clenbuterol, was used to determine the extent to which the responses to nylidrin were due to beta-receptor mediated action. Clenbuterol had similar effects on the b-wave and optic nerve response at slightly higher concentrations (30 200 microM) but more variable effects on the c-wave. The data are interpreted as functional evidence that beta adrenergic mechanisms are involved in retinal signal processing. This concept is corroborated by identification of beta-adrenergic binding sites in cat retina (Bruinink et al., 1986). PMID- 2892657 TI - Effects of short- and long-term administrations of famotidine and ranitidine on some pituitary, sexual and thyroid hormones. AB - The endocrine effects of short-term (4 weeks) and long-term (6 months) oral administration of famotidine (40 and 20 mg nocte, respectively) and ranitidine (300 and 150 mg nocte, respectively), were investigated in 20 male patients with duodenal ulcers. Basal PRL, LH, FSH and TSH serum levels were evaluated and their response to specific releasing factors, and basal blood levels of some sexual (E2, P, T) and thyroid (T3, T4) hormones. None of the treatments modified basal and RH-stimulated levels of PRL, LH, FSH and TSH, nor basal levels of sexual hormones. Regarding the thyroid hormones, no effect was observed during the administration of famotidine. On the contrary, short-term treatment with ranitidine induced a significant decrease in thyroxine serum levels, while no effect was observed during maintenance treatment. PMID- 2892658 TI - Action of famotidine and ranitidine on prostaglandin E2 (PGE2) content of fundic and duodenal mucosa in duodenal ulcer patients. AB - PGE2 plays an important role in gastric cytoprotection. Previous experience has shown that H2-blocker drugs may have a role in gastric cytoprotective mechanisms. The effects have been compared of ranitidine and famotidine on PGE2 content in duodenal ulcer patients. Twenty patients were treated for 4 weeks as follows: group A, ranitidine (150 mg twice daily); group B, famotidine (40 mg daily). The patients underwent EGDS before and after therapy. The results show that both famotidine and ranitidine significantly increase the PGE2 content of fundic mucosa (from 112.3 +/- 73 to 210.7 +/- 106 ng/g wet wt and from 109.6 +/- 52.4 to 230.2 +/- 104.6 ng/g wet wt, respectively) in duodenal ulcer patients (p less than 0.01). Similarly, the PGE2 content of duodenal mucosa significantly increases after famotidine treatment (from 51.9 +/- 27.5 to 105.3 +/- 55.6 ng/g wet wt) as well as ranitidine treatment (from 53.8 +/- 24 to 172.6 +/- 72.9 ng/g wet wt) (p less than 0.01). It is concluded that these drugs play an important role in gastric and duodenal cytoprotection. PMID- 2892659 TI - Astemizole: a long-acting, nonsedating antihistamine. AB - Astemizole is a long-acting, highly selective histamine1-receptor antagonist with minimal central and anticholinergic effects. Comparison studies have shown astemizole to be equal or superior to currently available antihistamines, beclomethasone nasal spray, and cromolyn sodium in relieving allergic symptoms of seasonal and perennial allergic rhinitis. Other uses include treatment of allergic conjunctivitis and chronic urticaria. Astemizole is not as effective for treatment of acute allergic symptoms because of its delayed onset of action. Astemizole and its active metabolite, desmethylastemizole, have long elimination half-lives permitting once-daily dosing. The incidence of sedation is lower than with conventional antihistamines, but increased appetite and weight gain do occur. Astemizole should be useful for both maintenance and prophylactic therapy in patients with chronic allergic conditions who cannot tolerate the sedative or anticholinergic effects of conventional antihistamines. PMID- 2892660 TI - [Acute myocardial infarct in patients over 70. Results of a 2-year survey]. AB - 581 consecutive patients admitted to hospital for acute myocardial infarction between January 1983 and June 1985 were divided into two groups. Group A (286) patients were aged 70 years or over (76 +/- 4 years); those in group B (246) were 65 or younger (56 +/- 8 years). Group A patients had a significantly higher incidence of anterior-wall infarction (30% vs. 18% in group B); heart failure (55% vs. 32%); pulmonary oedema (18% vs. 6%); cardiogenic shock (17% vs. 6.5%); or rupture (6% vs. 2%). Patients of the older age group also significantly less often underwent systemic fibrinolysis (0.3% vs. 21%); coronary angiography (2% vs. 61%); percutaneous transluminal coronary angioplasty (PTCA) or aorto-coronary bypass operation (0% vs. 22%) (P = 0.00001). Among the older patient group the cumulative mortality rate during hospitalization was 26.9% vs. 11.8% in group B, after six months it was 39% vs. 15%, after 12 months 46% vs. 17%, and after 24 months 61% vs. 21% (P = 0.00001). Causes of death were comparable in the two age groups, cardiac ones predominating. Angina in NYHA classes III-IV after discharge was present in 10% of the younger but 38% among the older patients (P = 0.00001). The death rate in patients of group A was very high under conservative treatment and surviving patients had a poor quality of life. Yet both coronary artery surgery and PTCA gave demonstrably better long-term results, both as to function and survival. Therefore, patients of even this higher age should more than is the case at present be more aggressively treated with invasive diagnostic and therapeutic procedures. PMID- 2892661 TI - [Systemic necrotizing vasculitis with bronchial asthma and eosinophilia: Churg Strauss syndrome]. AB - Two cases of the Churg-Strauss syndrome are reported, seen within the past year. The first concerned a 31-year-old woman with a rapidly progressive illness characterized by bronchial asthma, leukocytosis and eosinophilia, abdominal pain, diarrhoea and purpura. In the second case, a 47-year-old man had granulomatous epididymitis and interstitial nephritis before the asthma and eosinophilia developed. In both the diagnosis was confirmed by lung biopsy. Immunosuppressive treatment achieved rapid regression of all symptoms and of the eosinophilia, without recurrence so far. PMID- 2892662 TI - Ocular levobunolol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. AB - Levobunolol is a potent non-selective beta-adrenoceptor blocking agent used for the topical treatment of increased intraocular pressure in patients with chronic open angle glaucoma or ocular hypertension. In comparative studies of up to 2 years' duration levobunolol 0.5 to 1% reduced intraocular pressures by about 30% and adequately controlled intraocular hypertension in 50 to 85% of those treated. These results were significantly superior to those produced by placebo and comparable to the responses achieved with ocular timolol in double-blind controlled trials. Levobunolol has been well tolerated, producing only minor changes in objective and subjective ophthalmic and systemic parameters. Adverse reactions resulted in approximately 5% of patients withdrawing from treatment with levobunolol which was equivalent to that observed with timolol. Thus, ocular levobunolol is a well-tolerated and effective therapy for the management of raised intraocular pressure, and is a suitable alternative to ocular timolol in patients with chronic open angle glaucoma or ocular hypertension. PMID- 2892663 TI - [Physiopathology and curative treatment of tardive dyskinesia]. AB - Tardive dyskinesia is a common complication of neuroleptic treatment. Current physiopathological theories emphasize the role of dopaminergic, cholinergic and GABAergic systems. The experimental bases of these hypotheses have been presented in detail. A critical review of the main clinical trials allows us to evaluate the effectiveness of our treatment and the validity of our theoretical models. PMID- 2892665 TI - The effect of hypophysectomy and growth hormone administration on pre prosomatostatin messenger ribonucleic acid in the periventricular nucleus of the rat hypothalamus. AB - Physiological evidence suggests that hypothalamic somatostatin (SS) inhibits pituitary GH release and that GH acts through a short-loop feedback mechanism to stimulate SS secretion. The feedback action of GH could be mediated by an effect on SS synthesis, secretion, or both. We hypothesized that GH acts to regulate the expression of the SS gene and that changes in the level of circulating GH would result in corresponding changes in SS mRNA in cells of the periventricular nucleus (PeN) of the hypothalamus. To test this hypothesis we measured the effect of hypophysectomy (HPX) and HPX with bovine GH (bGH) replacement on SS mRNA signal levels in cells of the PeN of the rat brain. We report that HPX male rats treated with bGH have significantly higher PeN SS mRNA signal than their vehicle treated controls (P less than 0.05) and that bGH administration to sham-HPX rats results in elevated PeN SS mRNA signal levels compared to those in sham-HPX rats treated with vehicle (P less than 0.05). These observations suggest that GH participates in the regulation of its own secretion by influencing the expression of the SS gene and that one mechanism of short-loop pituitary feedback may involve the modulation of neuropeptide gene expression. PMID- 2892664 TI - Beta-adrenergic stimulation of growth hormone (GH) release in vivo, and subsequent inhibition of GH-releasing factor-induced GH secretion. AB - In vivo and in vitro studies of beta-adrenergic influences on GH secretion have produced apparently conflicting data in which the in vivo effect seems to be inhibitory and the in vitro effect to be stimulatory. The present studies were designed to observe the in vivo effect of isoproterenol (ISO), a beta-adrenergic agonist, on 1) GH release during a brief interval after intraatrial infusion, and 2) GH release in response to GRF infused 10 min after ISO. ISO was found to stimulate GH release in both intact and hypothalamus-lesioned animals within 2 min after infusion, but GH returned to control levels within 10 min. ISO also profoundly inhibited the release of GH in response to GRF. Pretreatment of animals with somatostatin (SRIF) antiserum prevented the inhibitory action of ISO on GRF-induced GH release. No change in peripheral levels of SRIF was detected. Also, there was no suppression of GRF-induced GH release by ISO when the treatments were applied in vitro to dispersed perifused pituitary cells. These data show that beta-adrenergic systems can stimulate a rapid but brief release of GH in vivo, and that the subsequent inhibitory action on GRF-induced GH release might be by means of SRIF release. PMID- 2892666 TI - Cloning of estrogen-regulated messenger ribonucleic acids from rat uterus. AB - A cDNA library prepared from the mRNA of uteri of estrogen-stimulated immature female rats was constructed in lambda gt10. Differential screening of the hybrid phages was performed using control and stimulated cDNAs as probes. Selected clones were then characterized by Northern and Southern blot hybridizations. In all, eight unique clones corresponding to estrogen-stimulated messages in rat uterus were identified. These clones hybridized to uterine mRNAs varying in size from 1.4-8.4 kilobases. Three of the clones were characterized as coding for three different types of collagen, and one as coding for smooth muscle actin. These are described in more detail elsewhere. The kinetics of increase in estrogen-regulated messages was examined. After a single injection of estradiol, five clones, including the three collagen mRNAs, showed two peaks of accumulation, at 4 and 24 h. Messages of two other clones were maximal at 12 h. The actin clone hybridized to mRNAs with peaks at 4 h for cytoskeletal actins and 8-12 h for smooth muscle actins. Sequential 24-h injections of the hormone produced multiple peaks of mRNA accumulation with a timing consistent with the kinetics found after a single injection of hormone. The multiple injections, however, did not result in enhanced mRNA accumulation for any of these clones. In fact, several messages showed suppressed accumulation with continued estradiol administration. Accumulated inhibitory factors in uterine cells may be responsible for this refractory condition. Except for the actin mRNA, the estradiol-stimulated mRNAs were expressed mainly in uterus and ovary. These clones may be useful in studies on the mechanism of action of estrogenic hormones and their tissue-specific regulation of gene expression. PMID- 2892667 TI - Alpha 1-adrenergic potentiation of vasoactive intestinal peptide stimulation of rat pinealocyte adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate: evidence for a role of calcium and protein kinase-C. AB - alpha 1-Adrenergic agonists have recently been found to potentiate vasoactive intestinal peptide (VIP) stimulation of rat pinealocyte cAMP and cGMP. alpha 1 Adrenergic agonists also elevate pineal intracellular Ca2+ [( Ca2+]i) and activate protein kinase-C. In the present study, the possible involvement of Ca2+ and protein kinase-C in the alpha 1-adrenergic potentiation of VIP-stimulated cAMP and cGMP accumulation was examined with agents that alter [Ca2+]i or activate protein kinase-C. It was found that treatment with a Ca2+ chelator or with inorganic Ca2+ channel blockers inhibited alpha 1-adrenergic potentiation of VIP-stimulated cAMP and cGMP responses. Increasing [Ca2+]i by treatment with A23187, ouabain, or K+ potentiated VIP stimulation of cAMP and cGMP response. These observations indicate that Ca2+ mediates the alpha 1-adrenergic potentiation of VIP-stimulated cAMP and cGMP accumulation, as is true for the alpha 1-adrenergic potentiation of beta-adrenergic stimulated cAMP and cGMP accumulation. Activators of protein kinase-C mimicked the large effect alpha 1 adrenergic agonists have on cAMP accumulation in VIP-treated pinealocytes and had a small effect on cGMP accumulation in VIP-treated cells. These effects were not blocked by the Ca2+ chelator EGTA. However, the effects of a protein kinase-C activator on the cGMP response in VIP-stimulated cells were amplified by K+ (15 mM) or ouabain (1 microM), presumably through an action causing an increase in [Ca2+]i. These results suggest protein kinase-C is involved in the alpha 1 adrenergic potentiation of VIP-stimulated cAMP accumulation, as is the case for the alpha 1-adrenergic potentiation of beta-adrenergic stimulated cAMP. Protein kinase-C is also involved in cGMP accumulation, provided that there is a modest increase in [Ca2+]i. PMID- 2892669 TI - Mitochondrial protein import: involvement of the mature part of a cleavable precursor protein in the binding to receptor sites. AB - The precursor of F0-ATPase subunit 9 was bound to mitochondria in the absence of a mitochondrial membrane potential (delta psi). Binding was mediated by a protease-sensitive component on the mitochondrial surface. When delta psi was reestablished, bound precursor was directly imported without prior release from the mitochondrial membranes. A chimaeric protein consisting of the complete subunit 9 precursor fused to cytosolic dihydrofolate reductase (DHFR) was also specifically bound to mitochondria in the absence of delta psi. Two other fusion proteins, consisting either of the entire presequence of subunit 9 and DHFR or of part of the presequence and DHFR, were imported in the presence of delta psi. In the absence of delta psi, however, specific binding to mitochondria did not take place. We suggest that the hydrophobic mature part of subunit 9 is involved in the delta psi-independent binding of the subunit 9 precursor to receptor sites on the mitochondrial surface. PMID- 2892668 TI - The human mdr3 gene encodes a novel P-glycoprotein homologue and gives rise to alternatively spliced mRNAs in liver. AB - We have found cDNAs corresponding to a novel human P-glycoprotein gene in liver cDNA banks. The sequence of the 3' part of this cDNA reveals a domainal organization of the derived protein similar to that of the known P-glycoproteins and an 80% amino acid homology with the product of the human mdr1 gene (Chen et al., 1986). The new gene lies within 500 kb from mdr1 as determined by pulsed field gradient gel electrophoresis and is designated mdr3, as it appears to correspond to the third of the three P-glycoprotein genes mapped in the hamster multidrug resistance domain. mdr3 yields a transcript of 4100 nucleotides, 400 nucleotides less than the mdr1 transcript; the difference is accounted for by the shorter 3'-untranslated region of the mdr3 mRNA. Our cDNAs provide evidence for alternative splicing of mdr3 pre-mRNAs. One alternative is an insert of seven amino acids between the two major blocks of the nucleotide binding site and another is a deletion of 43 or 47 amino acids covering the putative transmembrane segment 5a. We speculate that these alternatives superimposed on differential expression of P-glycoprotein homologues could provide an explanation for the large variation in cross-resistance patterns observed in cell lines selected for multidrug resistance with different cytostatic drugs. PMID- 2892671 TI - Atrial natriuretic factor receptor heterogeneity and stimulation of particulate guanylate cyclase and cyclic GMP accumulation. AB - Since the seminal discovery by deBold that atria contain factors that produce diuresis and natriuresis, the biologic effects attributed to ANF have expanded to the point where the name "atrial natriuretic factor" seems inappropriate. In addition to promoting diuresis and natriuresis, ANF has been shown to produce vascular smooth muscle relaxation and to inhibit the secretion of aldosterone from the adrenal cortex, renin from the juxtaglomerlular apparatus, vasopressin from the hypothalamus, and salt and water intake after central administration. ANF also promotes intestinal secretion and stimulates testosterone synthesis in Leydig cells. However, the cellular mechanisms whereby ANF elicits these diverse effects are poorly understood. ANF has been reported to inhibit adenylate cyclase in a number of tissues. However, the significance of ANF inhibition of adenylate cyclase is unknown. This effect cannot be associated with vascular relaxation since decreased cyclic AMP would be expected to promote contraction rather than relaxation. ANF inhibition of adenylate cyclase may mediate the inhibitory effects of ANF on hormone secretion from the anterior pituitary gland. The inhibition of adenylate cyclase could also explain the inhibitory effect of ANF on aldosterone synthesis, since agents that stimulate cyclic AMP increase aldosterone synthesis. However, ANF also inhibits the dibutyryl-cyclic AMP induced stimulation of aldosterone secretion, suggesting that an inhibition of adenylate cyclase cannot account fully for the inhibitory effects of ANF on aldosterone synthesis. There is no evidence to support a role for cyclic AMP in the diuretic and natriuretic action of ANF. An inhibition of membrane phosphoinositide breakdown by ANF and the subsequent formation of IP3 and intracellular calcium release could explain the inhibitory effects of ANF on vascular contraction and steroid synthesis. However, there is very little evidence to suggest that ANF regulates phosphoinositide metabolism, while some recent studies suggest that ANF may regulate calcium fluxes in vascular tissue. Clearly, cyclic GMP has emerged as the most likely intracellular mediator of ANF effects. ANF increases cyclic GMP in a wide range of tissues by selectively activating particulate guanylate cyclase. However, it is not known which effects of ANF are mediated by cyclic GMP. The discovery that ANF increases cyclic GMP in vascular tissue clearly suggests that cyclic GMP mediates the vascular relaxation effect of ANF, since other classes of vasodilators also increase cyclic GMP. There is preliminary evidence that cyclic GMP may inhibit renin secretion and sodium transport in kidney cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2892670 TI - DCCD inhibits protein translocation into plasma membrane vesicles from Escherichia coli at two different steps. AB - In vitro translocation of periplasmic and outer membrane proteins into inverted plasma membrane vesicles from Escherichia coli was completely prevented by the H+ ATPase inhibitor N,N'-dicyclohexylcarbodiimide (DCCD). DCCD was inhibitory to both co- and post-translational translocations, suggesting an involvement of the H+-translocating F1F0-ATPase in either mode of transport. This was verified by (i) the dependence of efficient co-translational translocation upon a low salt, i.e. F1-containing extract from membrane vesicles; (ii) the co-purification of the translocation activity present in this extract and F1-ATPase; (iii) the inability of either vesicles or their low-salt extract, derived from F1F0-ATPase lacking mutant strains, to support translocation; and (iv) the greatly diminished extent of ATP-dependent, post-translational translocation into F1-deprived vesicles. Membranes devoid of F1 did show, however, residual translocation activity that was also found to be inhibitable by DCCD. These results suggest a dual target for DCCD in bacterial protein export, one being the H+-ATPase and the other an as yet unidentified translocation factor. PMID- 2892672 TI - Influence of age on neurotransmitter function. AB - Regulation by neurotransmitters of anterior pituitary hormone secretion is complex and a thorough understanding of their normal role in hormone secretion is a prerequisite to understanding their involvement in age-related changes in endocrine function. To date, uncertainties far out-number demonstrated causative relationships between alterations in neurotransmitter release and resulting age associated changes in hormone secretion. The best demonstrated relationships are the following. First, a decline in function of the TIDA system is responsible, in part, for the age-related elevation in prolactin secretion and may be involved in the decline in LH secretion. Second, the age-related decrease in hypothalamic norepinephrine turnover plays a role in the decline in LH and GH secretion and may be involved in alterations in TSH secretion during aging. Third, the decline in circadian activity of suprachiasmatic nucleus serotoninergic neurons may account for the blunting of circadian rhythms in the secretions of several anterior pituitary hormones in old animals. Fourth, evidence exists for an age related decline in function of LHRH neurons, which may contribute to the observation of blunted LH secretion in old animals. Finally, somatostatin release may be increased in old animals, which likely contributes to the age-related decline in GH secretion. Other hypothalamic-releasing hormones have only recently been isolated and characterized; thus, little research on their age-related alterations has been done. Research on these neuropeptides will contribute further to our understanding of the role of neurotransmitters in age-related alterations in hormone secretion. PMID- 2892673 TI - Age-related changes in membrane receptor interactions. AB - The relevance of membrane receptor systems to aging in animals has been studied extensively. A large number of hormones, drugs, and transmitters convey their signals via membrane receptors. Many physiologic and biochemical processes are mediated via membrane receptors. Therefore, exploration of the age-related changes in the interactions of receptors with coupling proteins second-messenger systems and their surrounding environments are of obvious significance. PMID- 2892674 TI - Workshop on the relationship between short-term information and carcinogenicity; Williamsburg, Virginia, January 20-23, 1987. PMID- 2892675 TI - Comments and perspective on the EPA workshop on "The relationship between short term test information and carcinogenicity". PMID- 2892676 TI - Ova, larvae and cysts in fingernail contents. PMID- 2892677 TI - F0 part of the ATP synthase from Escherichia coli. Influence of subunits a, and b, on the structure of subunit c. AB - Four different sets of proteoliposomes were prepared from F0, subunit c, a complex of subunits a and c (ac complex) and an ac complex supplemented with subunit b. Only liposomes containing intact F0 or all subunits of F0 were active in proton translocation and F1 binding [Schneider, E. and Altendorf, K. (1985) EMBO J. 4, 515-518]. The conformation of subunit c in the different preparations was analyzed by labelling the proteoliposomes with the hydrophobic photoactivatable reagent 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine ([125I]TID). Subsequent isolation and Edman degradation of this polypeptide revealed distinct radioactive labelling patterns over the entire amino acid sequence. In the F0 complex and in the ac complex subunit c retains a labelling pattern which is related to that found in TID-labelled membrane vesicles of Escherichia coli [Hoppe et al. (1984) Biochemistry 23, 5610-5616]. In the absence of subunit a, considerably more and different amino acid residues of subunit c are modified. The labelling data are discussed in relation to structural aspects of F0 and functional properties of proteoliposomes reconstituted with F0 or individual subunits. PMID- 2892678 TI - ATP4, the structural gene for yeast F0F1 ATPase subunit 4. AB - A plasmid containing the gene coding for the Saccharomyces cerevisiae F0F1 ATPase subunit 4 was isolated from a yeast genomic DNA library using the oligonucleotide probe procedure. The gene and the surrounding regions were cloned into M13 tg 130 and M13 tg 131 phage vectors. A 732-base-pair open reading frame encoding a 244 amino-acid polypeptide is described. The nucleotide sequence predicts that subunit 4 is probably derived from a precursor protein with a hydrophilic and basic 35-amino-acid leader sequence. Mature subunit 4 contains 209 amino acid residues and the predicted molecular mass is 23250 Da. This subunit presents amphiphilic behaviour with two distinct domains. A high alpha-helix content of 77% was predicted from the sequence. Subunit 4 shows homology with the b subunit of Escherichia coli ATP synthase. PMID- 2892679 TI - Purification in large scale and characterization of the human leukocyte adhesion glycoprotein GP90 (CD18). AB - The leukocyte adhesion 90-kDa glycoprotein GP90 (antigen CD18) is non-covalently associated separately with cell-surface glycoproteins GP160 (antigens CD11a, TA 1, LFA-1), GP155 (antigens CD11b, OKM1, MO1) or GP130 (antigens CD 11c, Leu-M5). Large amounts of these protein complexes were purified to homogeneity from blood mononuclear leukocytes by immunoaffinity chromatography using a monoclonal antibody. GP90 was further isolated by preparative gel electrophoresis in the presence of sodium dodecyl sulfate. Rabbit antiserum towards the complex inhibited phorbol-ester-induced adhesion of leukocytes. The antiserum towards purified GP90 reacted more strongly with the denatured GP90 protein, but showed reactivity also with GP160 protein, indicating structural homologies between GP90 and GP160. The amino acid composition of GP90 was determined. Its N-terminus was found to be blocked. Treatment of GP90 with endo-beta-N-acetylglucosaminidase F, but not with endo-beta-N-acetylglucosaminidase H, reduced the apparent molecular mass to 75 kDa, indicating the presence of five or six N-linked complex-type oligosaccharides/molecule. PMID- 2892680 TI - The secondary structure of the toxin ATX Ia from Anemonia sulcata in aqueous solution determined on the basis of complete sequence-specific 1H-NMR assignments. AB - The toxin preparations ATX I, ATX Ia and ATX Ib from Anemonia sulcata were investigated by proton nuclear magnetic resonance (NMR). High-resolution phase sensitive two-dimensional NMR experiments were used to monitor the separation by high-performance liquid chromatography of the two isoproteins ATX Ia and ATX Ib. For ATX Ia complete sequence-specific resonance assignments were obtained and the secondary structure was determined. To obtain the NMR assignments we used a variant of the sequential assignment technique which relied extensively on cross peak fine-structure analysis in phase-sensitive spectra, using spectrum simulations based on density matrix calculations with the program SPHINX. These procedures, which resulted in extensive amino acid spin system identifications prior to the sequential assignments, should be generally applicable for small proteins with relatively narrow 1H-NMR lines. The secondary structure of ATX I includes a beta sheet consisting of four strands. No evidence was found for the presence of regular helical segments. The four beta strands are connected by two extended loops and a tight turn, for which further characterization has to await the complete determination of the three-dimensional structure. PMID- 2892681 TI - ADP-ribosylation of skeletal muscle and non-muscle actin by Clostridium perfringens iota toxin. AB - The enzymatically active component ia of Clostridium perfringens iota toxin ADP ribosylated actin in human platelet cytosol and purified platelet beta/gamma actin, in a similar way to that been reported for component I of botulinum C2 toxin. ADP-ribosylation of cytosolic and purified actin by either toxin was inhibited by 0.1 mM phalloidin indicating that monomeric G-actin but not polymerized F-actin was the toxin substrate. Perfringens iota toxin and botulinum C2 toxin were not additive in ADP-ribosylation of platelet actin. Treatment of intact chicken embryo cells with botulinum C2 toxin decreased subsequent ADP ribosylation of actin in cell lysates by perfringens iota or botulinum C2 toxin. In contrast to botulinum C2 toxin, perfringens iota toxin ADP-ribosylated skeletal muscle alpha-actin with a potency and efficiency similar to non-muscle actin. ADP-ribosylation of purified skeletal muscle and non-muscle actin by perfringens iota toxin led to a dose-dependent impairment of the ability of actin to polymerize. PMID- 2892682 TI - Inhibition of mitochondrial F1 ATPase and sarcoplasmic reticulum ATPase by hydrophobic molecules. AB - The hydrophobic nature of the active site of two energy-transducing ATPases was explored by comparing interactions between Pi and each of three hydrophobic drugs in the absence and presence of organic solvents. The drugs tested were the Fe . bathophenanthroline complex and the anticalmodulin drugs, calmidazolium and trifluoperazine. All inhibit the Pi in equilibrium with ATP exchange reaction catalyzed by submitochondrial particles and the ATPase activity of both submitochondrial particles and soluble F1 ATPase. The inhibition by the three drugs is reversed by either raising the Pi concentration or by adding organic solvent (dimethylsulfoxide, ethyleneglycol or methanol) to the medium. The inhibition of the Pi in equilibrium with ATP exchange by trifluoperazine becomes more pronounced when the electrochemical proton gradient formed across the membrane of the submitochondrial particles is decreased by the addition to the medium of the proton ionophore carbonylcyanide p-trifluoromethoxyphenylhydrazone. The ATPase activity and the Ca2+ uptake by sarcoplasmic reticulum vesicles are inhibited by the Fe . bathophenanthroline complex, calmidazolium and trifluoperazine. Phosphorylation of the ATPases by Pi, synthesis of ATP from ADP and Pi and the fast efflux of Ca2+ observed during reversal of the Ca2+ pump are inhibited by the three drugs. The inhibition is reversed by raising the concentration of Pi or dimethylsulfoxide. The three drugs tested appear to compete with Pi for a common binding site on the Ca2+-ATPase. The data presented are interpreted according to the proposal that the catalytic site of an enzyme involved in energy transduction undergoes a hydrophobic-hydrophilic transition during the catalytic cycle. PMID- 2892683 TI - Early diagnosis in X-linked agammaglobulinaemia. AB - The genetic transmission of X-linked agammaglobulinaemia (XLA) can be determined with high probability using closely linked DNA restriction fragment length polymorphisms (RFLP's). In a family known to be at risk for XLA in male offspring, RFLP analysis demonstrated that the mother was an XLA carrier and her newborn son was affected. The infant developed immunological deficiencies a few months later, confirming the diagnosis. RFLP analysis provides a method for carrier detection, prenatal diagnosis and presymptomatic diagnosis of XLA, which plays a significant role in prevention of the disease. PMID- 2892684 TI - Inhibition of non-dopamine cells in the ventral tegmental area by benzodiazepines: relationship to A10 dopamine cell activity. AB - Previous electrophysiological studies have demonstrated that non-dopaminergic (non-DA) neurons within the substantia nigra pars reticulata (SNR) are extremely sensitive to the inhibitory effects of GABA and GABA-mimetic drugs, including benzodiazepines, whereas dopaminergic (DA) neurons in the substantia nigra pars compacta (SNC) are less sensitive to these compounds and may be influenced indirectly by SNR neurons. The interactions between A10 DA and non-DA neurons within the adjacent ventral tegmental area (VTA) are not as well characterized. In the present experiments, single unit recording and microiontophoretic techniques were used to determine the effects of benzodiazepines on DA and non-DA neurons in the VTA of chloral hydrate anesthetized rats. Diazepam, administered intravenously (i.v.), potently inhibited non-DA, SNR-like cells within the VTA. The effects of diazepam on A10 DA cells were more variable than those observed on non-DA, SNR-like cells in this region, but 77% of such cells showed moderate to marked excitation. Both of these effects were reversed by the benzodiazepine antagonist Ro 15-1788; on many cells, this agent produced marked rebound effects beyond the original basal firing rates. However, when administered alone, Ro 15 1788 exerted no effect on either cell population. Microiontophoretic administration of the benzodiazepines chlordiazepoxide and flurazepam resulted in marked inhibition of non-DA SNR-like cells, but produced either mild inhibition or no effect on A10 DA cells; excitation of DA cells was never observed even though the same neuron was excited by i.v. diazepam. These findings suggest that benzodiazepines act directly upon non-DA, SNR-like cells in the VTA to produce inhibition of activity and a disinhibition of A10 DA cells. This relationship makes it unlikely that benzodiazepines would enhance feedback inhibition of DA cells following neuroleptic administration. In fact, when administered following haloperidol, i.v. diazepam failed to reverse haloperidol-induced increases of A10 DA cell firing; if anything, diazepam further depolarized the cell. If antipsychotic drugs produce their clinical effects, in part, by inducing depolarization inactivation of DA cells, then benzodiazepines might be a useful adjunctive therapy in the treatment of schizophrenia. PMID- 2892685 TI - [3H]Ro 15-1788 binding to benzodiazepine receptors in mouse brain in vivo: marked enhancement by GABA agonists and other CNS drugs. AB - Administration of the benzodiazepine receptor antagonist, [3H]Ro 15-1788, to mice intravenously was found to label these receptors in brain. Binding of [3H]Ro 15 1788 in vivo was strongly blocked by pretreating mice with clonazepam or diazepam. Marked enhancement of [3H]Ro 15-1788 binding in vivo was induced by progabide or sodium valproate. This effect was greater than a similar enhancement of [3H]flunitrazepam binding. The increased membrane-bound [3H]Ro 15-1788 elicited by progabide was completely dissociated on subsequent incubation with Ro 15-1788, diazepam or clobazam, indicating that the enhanced binding occurred at benzodiazepine receptors. Compounds that exert diazepam-like actions and/or indirect GABAergic activity (cartazolate, pentobarbital, methaqualone, levonantradol, phenytoin) elicited enhancement of [3H]Ro 15-1788 in vivo. Other CNS agents (atypical neuroleptics, GABA antagonists, baclofen, some 5-HT1 agonists) also induced elevation of [3H]Ro 15-1788 binding in vivo, as did drugs exerting vasodilatatory effects (papaverine, nimodipine, verapamil, prazosin, N6 cyclohexyladenosine). Possible explanations for enhancement of [3H]Ro 15-1788 binding in vivo include increase in the number of benzodiazepine receptors induced by GABA or GABAergic drugs or effects of binding enhancers that elevate brain levels of [3H]Ro 15-1788, such as accelerating cerebral blood flow, competing for radioligand binding sites in plasma or increasing metabolic stability of the radioligand. PMID- 2892686 TI - Stress-induced insomnia: opioid-dopamine interactions. AB - REM sleep deprivation induced by means of the platform technique (72 h) was followed by a period of latency to sleep characterized by a marked excitement in rats. The administration of naloxone at the end of the REM deprivation period reduced this latency to sleep while morphine, beta-endorphin and DADLE prolonged it. The dopamine D1 receptor antagonist SCH 23390 was extremely potent (0.003 mg/kg) to reduce the latency to sleep and the excitement while the D1 agonist SKF 38393 induced an opposite effect. The dopamine D2 receptor antagonist L-sulpiride was inactive up to a dose of 25 mg/kg. These data suggest that hyperactivity of the opioid and dopamine systems (specifically mediated through D1 receptors) is involved in such behaviour. PMID- 2892687 TI - Effect of ethanol on cardiac beta-adrenoceptors. AB - Liquid diets are commonly used as vehicles for chronic administration of ethanol to rodents. After mice had consumed an ethanol-free liquid diet for either seven or eight days, the number of cardiac beta-adrenoceptors and the maximum response of adenylate cyclase to isoproterenol were decreased. This change was associated with a decrease in the number of high-affinity agonist binding sites. When mice were fed ethanol in the liquid diet, there was a further decrease in the number of cardiac low-affinity agonist (isoproterenol) binding sites, but no further change in the biochemical response to isoproterenol. The data suggest that stress and/or nutritional factors can alter the number, the coupling and the function of cardiac beta-adrenoceptors and that chronic ethanol ingestion enhances certain aspects of these changes. PMID- 2892688 TI - Autoradiographic localization of dopamine D1 binding sites in areas receiving striatal input. PMID- 2892689 TI - The disappearance of a cyclin-like protein and the appearance of statin is correlated with the onset of differentiation during myogenesis in vitro. AB - We have used monoclonal antibodies to statin (S-44) and a cyclin-like protein (S 132) to examine the distribution of these two antigens in proliferating and in nonproliferating populations of cells. We have found that this cyclin-like protein is present in proliferating fibroblasts, whereas statin is absent from these same cell populations; in contrast, in senescent populations of fibroblasts the cyclin-like antigen disappears and statin labeling of nuclei appears. During myogenesis in rat muscle cell cultures, S-132 labeling is present in proliferating myoblasts and disappears after cells fuse and differentiate as multinucleated myotubes. In contrast, statin is absent from proliferating myoblasts, but appears when these cells become postmitotic and begin to differentiate. Similar results were seen during chick myogenesis. We have also found similar results during serum-starvation-induced differentiation in neuroblastoma cells. These results indicate that the cyclin-like protein disappears and statin appears upon commitment to differentiation in vitro, and the presence or the absence of these proteins appears to provide cellular markers for the transition from the proliferative to the nonproliferative state during differentiation. PMID- 2892690 TI - An antibody against 100- to 116-kDa polypeptides in coated vesicles inhibits triskelion binding. AB - There is considerable evidence that the 100- to 116-kDa polypeptides in calf brain coated vesicles are involved in the assembly of clathrin triskelions to form coated vesicles. We have raised polyclonal antibodies against these polypeptides. By Western blot analysis, these antibodies bind to a distinct subset of the six polypeptides in the region 100-116 kDa. Whole cell homogenates from calf brain, calf liver, and rat liver also show immunoreactivity in the 100 kDa region with no other cross reactivity. Isolated coated vesicles from calf liver, rat brain, and soybean roots also cross-react. Stripped coated vesicles, which are depleted of clathrin but which retain the 100- to 116-kDa polypeptides, quantitatively rebind 125I-triskelions. This binding is inhibited in a dose dependent manner by 100- to 116-kDa antibody but not by nonimmune serum or by anti-clathrin polyclonal antibody. These studies indicate that (1) specific sites on the 100- to 116-kDa polypeptides are required for assembly of coated vesicles, and (2) this antibody will be useful in clarifying more precisely the role of the 100- to 116-kDa polypeptides in coated vesicle recycling. PMID- 2892691 TI - Transformation of Tetrahymena thermophila by electroporation and parameters effecting cell survival. AB - We have successfully transformed Tetrahymena thermophila by electroporation, a process of electrically introducing DNA. The DNA used for transformation contains a mutant ribosomal RNA gene (rDNA) that confers resistance to paromomycin on the transformed cells. This mutant rDNA replicates more rapidly than the endogenous rDNA of the transformed cells so that the mutant rDNA becomes predominant within several generations. This mutant rDNA also carries a restriction polymorphism that readily distinguishes it from the endogenous rDNA of the transformed cells. Substantial nuclease activity is released from the cells during electroporation and must be neutralized in order for transformation to be effective. Cell survival is inversely proportional to the electrical energy dissipated (joules) in the medium. Electroporation is a convenient and effective means of introducing transforming DNA into T. thermophila. PMID- 2892693 TI - Effect of alpha-adrenergic and serotonergic blockers on the acute irritative response in the rabbit eye. AB - The effect of alpha-adrenergic and serotonergic (5-HT) blockers on the acute irritative response in the rabbit eye elicited by topical, neutral formaldehyde (1%), was studied. In the control animals, the peak rise in the intraocular pressure (delta IOP) after irritation was 29.5 +/- 5.7 mm Hg, and the perfusion pressure of the eye at 1 min after irritation was 50.1 +/- 2.8 mm Hg. The peak rise in the IOP was inhibited by phentolamine (alpha- and 5-HT-antagonist, delta IOP = 6.6 +/- 2.1 mm Hg, P less than 0.01), methysergide (5-HT-antagonist, delta IOP = 10.6 +/- 4.4 mm Hg, P less than 0.05), and prazosin (alpha 1-antagonist, delta IOP = 12.8 +/- 3.7 mm Hg, P less than 0.05). Perfusion pressures of the eyes were decreased after pretreatment with phentolamine or prazosin, and were 35.2 +/- 4.8 mm Hg (P less than 0.05) and 25.7 +/- 3.7 mm Hg (P less than 0.01), respectively. Perfusion pressure in the methysergide group remained unchanged (75.4 +/- 14.2 mm Hg). Yohimbine (alpha 2-antagonist) and ketanserin (5-HT2 antagonist) did not inhibit the IOP response. None of the antagonists could inhibit the miosis or disruption of the blood-aqueous barrier induced by topical neutral formaldehyde. In the contralateral eyes, the changes in the IOP, in the integrity of the blood-aqueous barrier, and also in the pupil size, were enhanced by ketanserin. The present study demonstrates the inhibitory actions of methysergide, phentolamine, and prazosin on the neurally mediated, acute irritative response in the rabbit eye. Methysergide seems to inhibit the response, probably acting via the 5-HT1-receptors. A part of the effect of phentolamine might be explained by an inhibitory action via 5-HT1-receptors. The effect of phentolamine and prazosin on the alpha 1-receptors seems to create an inhibitory action on the irritative response by lowering the perfusion pressure of the eye. PMID- 2892694 TI - Trypanosoma cruzi: immune response in mice immunized with parasite antigens. AB - The humoral and cellular immune responses were studied in mice immunized with flagellar fraction (F), F plus Bordetella pertussis as adjuvant (F-Bp), and microsomal (Mc) subcellular fractions from the epimastigote forms of Trypanosoma cruzi. The immune response was studied before and after the challenge with 50 bloodstream forms of T. cruzi, Tulahuen strain. The immunization with F-Bp, but not with Mc or F and Bp separately, protected mice, in terms of parasitemia and mortality, from the challenge with the parasite. Before the challenge, levels of specific antibodies in mice immunized with F-Bp were higher than in mice immunized with F or Mc. Antibody levels 17 days after the infection were similar in the three groups of mice while nonimmunized mice reached lower levels. Early during the infection nonimmunized infected mice lacked delayed-type hypersensitivity (DTH) responses to parasite antigens and to concanavalin A (Con A). Mice immunized with F-Bp, however, presented positive DTH responses to parasite antigens and Con A both, before and after the challenge with T. cruzi. DTH reaction was transferred with spleen cells. Mice immunized with Mc behaved similarly to infected nonimmunized animals in their reactivity to parasite antigens. These results indicated striking differences between protected and nonprotected mice in humoral and cellular immune responses during experimental T. cruzi infection. PMID- 2892692 TI - HTLV-1, HIV-1, hepatitis B and hepatitis delta in the Pacific and South-East Asia: a serological survey. AB - Blood samples from 13 locations in the Pacific and South-East Asia were tested for evidence of infection with human T-cell lymphotropic virus type-1 (HTLV-1), human immunodeficiency virus (HIV-1), hepatitis B virus (HBV) and hepatitis delta virus (HDV). No samples were positive for antibody to HIV-1. Antibodies to HTLV-1 were found in samples from five locations, the maximum prevalence being 19%, in Vanuatu. Serological markers of HBV infection were found in all locations, the maximal prevalence being 88%, in Majuro, Micronesia. Antibodies to HDV in HBsAg positive sera were found in six locations with a maximum prevalence of 81% in Kiribati. PMID- 2892697 TI - [Reactions of the secretory and myoepithelial cells of mammary alveoli to neuromediators and oxytocin]. AB - The hyperpolarization of the secretory cells MP and the alveolar myoepithelium contraction in response to oxytocin depend to a greater extent on the accompanying effects of catecholamines as compared with acetylcholine. The hyperpolarization of the secretory cells MP induced with oxytocin and acetylcholine diminishes in its amplitude and duration in presence of colchicine (25 microM). Rhythmic hyperpolarization changes of the MP induced with 1-minute action of oxytocin and acetylcholine coincide in time with the exocytosis period of secretory vesicles and the beginning of new biosynthesis. PMID- 2892695 TI - Negative regulation of atrial natriuretic factor receptor coupled membrane guanylate cyclase by phorbol ester. Potential protein kinase C regulation of cyclic GMP signal in isolated adrenocortical carcinoma cells of rat. AB - Rat adrenocortical carcinoma cells possess a high density of atrial natriuretic factor (ANF) receptors which are coupled with membrane guanylate cyclase and corticosterone production. Herein we show that pretreatment of these cells with phorbol 12-myristate 13-acetate (PMA), a known activator of protein kinase C, attenuates the ANF-stimulated cyclic GMP accumulation in a dose-dependent manner. The half maximum inhibitory concentration of PMA was 10(-10) M. When these cells were incubated with PMA in the presence of 1-(5-isoquinolinyl-sulfonyl)-2-methyl piperazine, a protein kinase C inhibitor, the PMA-mediated attenuation of ANF stimulated cyclic GMP formation is blocked. These results suggest that protein kinase C negatively regulates the ANF-receptor coupled membrane guanylate cyclase system in these cells. PMID- 2892696 TI - Synthesis of a photoaffinity-spin-labeled derivative of ATP and its first application to F1-ATPase. AB - The synthesis of an ATP derivative is described, in which a spin-label is attached to the 3'-position of the ribose moiety and an azido group to C8 of the adenine ring (SL-N3-ATP). Irradiation of this compound at 350 nm generates a nitrene, which will react with any functional group in its vicinity. SL-N3-ATP exhibits a strongly immobilized ESR spectrum in a complex with F1-ATPase from beef heart mitochondria. It was covalently incorporated into this enzyme. SL-N3 ATP may be employed in ESR investigations under conditions in which non-covalent interactions are too weak for motionally restricted species to be easily observed. PMID- 2892698 TI - Effects of cryptorchidism and orchidopexy on deoxyribonucleoside-activated nucleotidase (DAN) in the rat testis. AB - 1. Unilateral cryptorchidism was associated with an increase in specific DAN activity in the abdominal testis of adult rats. 2. In the scrotal, immature testis, there was an age-dependent decrease in specific DAN activity similar to that normally seen in rats. This decrease was less pronounced in the abdominal testis of unilaterally cryptorchid rats. 3. Total DAN activity in the abdominal testis showed a decrease in both immature and adult rats, when compared to that of the scrotal testis. 4. Orchidopexy following cryptorchidism in adult rats, resulted in complete restoration of DAN activity in spite of poor recovery of spermatogenesis. PMID- 2892700 TI - Emergency hysterectomy in obstetric practice: five year review. AB - From January 1980 to December 1984, there were 86,483 deliveries and 25 emergency obstetric hysterectomies at the Maternity Hospital, Kuwait. The indications for hysterectomy were placental disorders (64%), uterine rupture (28%), and extension of the lower uterine scar during cesarean section (8%). The incidence of emergency hysterectomy increased with age and parity. Postoperative morbidity was higher with subtotal than with total hysterectomy. The commonest post-operative complication was urinary tract infection. There was one maternal death from consumptive coagulopathy associated with intra-uterine fetal death. PMID- 2892699 TI - Antenatal iron supplementation in sickle cell disease. AB - Fourteen pregnant women with sickle cell disease (11 SS and 3 SC) were randomized into two groups to receive routine antenatal supplementation either with ferrous gluconate or with placebo tablets. Their hemoglobin levels and bone marrow iron content were determined prenatally and 6 weeks post partum. The fetal weights and the incidence of pain crisis in both groups were recorded. Using an iron content grading from 0 to 5, no marrow of any subject showed iron depletion. The placebo group showed an aggregate postnatal loss of 4 grades of iron repletion while the iron supplemented group showed an aggregate gain of 2 grades. There were no significant differences between the birth weight or the incidence of pain crises in both groups. We conclude that routine iron supplementation is not justified in pregnant women with sickle cell disease, as it would tend to increase already adequate or excessive iron body stores. We recommend that a clear need for iron should be established before iron supplementation is prescribed to them. PMID- 2892701 TI - Plasma fibronectin levels in normal pregnancy and pre-eclampsia: a preliminary report. AB - Fibronectin, a major component of the extracellular matrix and basement membranes throughout the body, is thought to maintain the integrity of both the reticulo endothelial system and microvasculature. In this study, plasma fibronectin levels were assayed by nephelometry in nine pre-eclamptic gravid women, nine normotensive gravid women and ten non-gravid women. The mean plasma fibronectin level (+/-S.E.M.) in pre-eclamptic gravidas (1687 +/- 101 micrograms/ml) is significantly higher than that of either normotensive gravidae (1129 +/- 99 micrograms/ml) or non-gravid women (897 +/- 60 micrograms/ml). Although the mechanism for elevated levels of plasma fibronectin in patients with pre eclampsia is not clear, it may serve as an early biochemical marker for this disorder. PMID- 2892702 TI - Subsequent pregnancy following labor of a very-low-birth-weight infant. AB - During a period of 5 years (1978-1982), 55 mothers with an average age of 27.5 +/ 5.4 years, delivered 59 infants, weighing less than 1500 g. These infants had a mean birth weight of 1160.5 +/- 263 g and a mean gestational age of 28.7 +/- 2.25 weeks (range 25-32 weeks). Subsequently 47 (79.6%) survived and 12 (20.4%) died. There was a statistical difference of both mean gestational age and of mean gestational weight between survivors or infants with neonatal death. Twenty two of 29 mothers who subsequently became pregnant, gave birth to liveborn infants, who subsequently survived (four pregnancies terminated in induced abortion). Mean gestational age was 37 +/- 3 weeks (range 32-41 weeks) (P less than 0.001) and a mean birth weight was 2753.2 +/- 570 g (range 1620-3600 g) (P less than 0.001. All the 22 infants subsequently born weighed more than 1501 g, 7 (31.8%) infants weighed 1501-2500 g and 15 (68.2%) more than 2500 g. Similar data were obtained from a control group of 615 mothers (chosen at random) who delivered a normal infant at term, 202 subsequently became pregnant and 176 gave birth to a normal infant at term. Mean gestational age was 39.54 +/- 1.24 weeks (P less than 0.001) and mean birth weight was 3299.3 +/- 412 g (P less than 0.001). (In the control group 10 pregnancies terminated in induced abortions). The above data could be used in advising for future pregnancy outcome in regard to women with premature births. PMID- 2892703 TI - Symphysiotomy as an alternative to cesarean section. AB - The author compares the value of symphysiotomy to cesarean section in the management of cephalopelvic disproportion. He outlines the history of the procedure and reviews the literature on the subject. He then presents results of 54 symphysiotomies performed from 1976 to 1983 in two rural hospitals in the southwestern highlands of Tanzania, together with the outcome of subsequent labor in 25 other women with a history of previous symphysiotomy. The risk of maternal mortality after symphysiotomy is lower than after cesarean section when performed for cephalopelvic disproportion. Although different in nature, maternal morbidity after both operations is equally common. In contrast with findings reported in the literature, a history of previous symphysiotomy still constitutes a high obstetrical risk. The author concludes that symphysiotomy has a place in the management of cephalopelvic disproportion. PMID- 2892704 TI - Endocrine and metabolic effects of simple hysterectomy. AB - A survey of 60 women who had undergone simple hysterectomy with preservation of ovaries revealed a high prevalence of menopausal flushes. Only 5 (8%) had menopausal concentrations of gonadotropins and estradiol. This is similar to the prevalence of natural menopause in population of comparable age. Of the remaining 55 women, 28 (47% of the total) had normal gonadotrophins and estradiol concentrations although they complained of hot flushes; these levels were not significantly different from those in 27 women who did not flush. The "flushers" did, however, have significantly diminished bone mineral index and higher serum uric acid concentrations than the "non-flushers". Flushes disappeared in those women who took estrogen replacement therapy. These data show that although full blown menopause does not increase in frequency following simple hysterectomy, a subtle diminution in estrogenisation is frequent. This hypo-estrogenisation is sufficient to cause: (a) hot flushes; (b) demineralisation of the skeleton and (c) an elevation in serum uric acid concentrations. There may be a case for estrogen therapy in all women who develop hot flushes following simple hysterectomy. PMID- 2892705 TI - Combined intrauterine and extrauterine gestation: a report of case history and review. AB - Combined intrauterine and extrauterine gestation is very rare. There is a higher maternal morbidity and fetal loss, due to delayed or missed diagnosis. We present a patient who was treated for primary infertility with ovulation induction agents, who presented later with combined intra- and extra-uterine gestation with successful outcome following delivery of a healthy male infant at 38 weeks gestation. PMID- 2892707 TI - Disseminated pelvic hydatidosis presenting as ovarian carcinomatosis: successful post-operative treatment with mebendazole. AB - The case of a female with disseminated pelvic cystic hydatidosis presenting as ovarian carcinomatosis 2.5 years after repeated abdominal paracentesis is reported. The diagnosis was made during surgery and confirmed by serology and histological examination. Over 100 cysts were removed from the abdominal cavity and wall. Innumerable small cysts studded the viscera; these and larger inaccessible ones were untouched. Medical cure in this patient was achieved with a combination of partial resection and special irrigation, broad spectrum antibiotic for coverage of infectious episodes and high dose long term mebendazole therapy for 25 months. The danger of blind aspiration in patients coming from endemic areas is emphasized. PMID- 2892706 TI - Endometriosis in the groin. AB - Recently we found one case of endometriosis in the extraperitoneal part of the round ligament (EERL). We found 30 cases previously described in the literature. A comparison showed that 90% were right-sided and often associated with an inguinal hernia. Fertility seemed to be below normal. In four of the cases a laporotomy was done. All had intraperitoneal endometriosis. In cases of EERL and claimed sterility therefore, the presence of intraperitoneal endometriosis should also be considered. PMID- 2892708 TI - The effect of oral contraceptive acceptance on fertility in the postpartum period. PMID- 2892709 TI - Breast feeding, contraception and fertility. Joint WHO/FIGO Task Force for the "Promotion of Maternal and Child Health, including Family Planning in Primary Health Care". PMID- 2892710 TI - The passage of exogenous hormones into breast milk--possible effects. PMID- 2892711 TI - The effects of contraceptive methods on the quality and quantity of breast milk. PMID- 2892712 TI - The effects of contraceptive use on the initiation and duration of lactation. PMID- 2892714 TI - Lactation and lactation related variables; contraception and fertility: an overview of data problems and world trends. PMID- 2892713 TI - Contraception during the postpartum period and during lactation: the effects on women's health. WHO Task Force on Oral Contraceptives. PMID- 2892715 TI - Breast-feeding and fertility: sociocultural factors. PMID- 2892716 TI - The biological basis for the contraceptive effects of breast feeding. PMID- 2892718 TI - The effects of hormonal and non-hormonal contraceptives on human lactation and on the re-establishment of fertility. PMID- 2892717 TI - Breast-feeding and the growth and development of the infant. PMID- 2892719 TI - The provision of contraceptive methods during lactation and support for breast feeding: policies and practice. PMID- 2892720 TI - Exposure to contraceptive hormones through breast milk--are there long-term health and behavioral consequences? PMID- 2892721 TI - Risk of pregnancy associated with maternal and child nutritional status. PMID- 2892722 TI - Breast-feeding and fertility: the sociocultural context. PMID- 2892723 TI - Acquired immunodeficiency syndrome (AIDS): a commentary on the international aspects of the disease. PMID- 2892724 TI - Radical vulvectomy for squamous cell carcinoma of the vulva. AB - Twenty-one patients with squamous cell carcinoma of the vulva who were subjected to radical vulvectomy and inguinal-pelvic lymphadenectomy were studied. The overall mortality rate was 24%. Operative- and tumor-related mortalities were 9.5% and 14.2%, respectively. Recurrence was seen in 5 patients. The most common complication was wound infection and breakdown. PMID- 2892725 TI - Evolution of cystic and adnexal tumors identified by echography. AB - The authors present their experience in detecting volume and echostructure alterations of the ovary in 14,525 women examined echographically and clinically. They analyzed 499 adnexal tumors and observed after clinical follow-up and echography that 60.6% of the cystic-septa tumors had involuted spontaneously. Percentage of spontaneous resolution was higher in small-diameter tumors, avoiding unnecessary surgery. PMID- 2892726 TI - The effects of maternal age and parity on birthweight: a population-based study in New York City. AB - New York City birth certificates for singletons born from September 1-December 31, 1981 (N = 36,056) were analyzed using multivariate regression techniques. The effects of maternal age and parity on birthweight were assessed. There was a significant progression of birthweight with advancing age. Birthweight similarly increased from parity 1 to parity 3, but dropped markedly in the higher parity groups. On stratification by gestational age, we found that age and parity influence birthweight by affecting fetal growth rather than the length of pregnancy. PMID- 2892727 TI - Progesterone challenge test and estrogen assays in menopausal women with endometrial adenomatous hyperplasia. AB - In an attempt to detect asymptomatic endometrial adenomatous hyperplasia in postmenopausal women, 40 cases were subjected to progesterone challenge test (PCT), measurement of serum estrogen and endometrial curettage. Group A (n = 30) included asymptomatic postmenopausal women, while group B (control group; n = 10) were cases with adenomatous hyperplasia (AH) diagnosed by biopsy. PCT showed a 100% sensitivity, 92% specificity, 71.4% predictive value of a positive test and 100% predictive value of a negative test in the detection of AH. Mean serum concentrations of E1 and E2 were significantly higher in patients with AH compared to cases with other endometrial histologies. Serum E1 and E2 and PCT can be used as screening tests to identify postmenopausal women with endometrial AH and thus at a greater risk of developing carcinoma. PMID- 2892728 TI - The effect of mesterolone on sperm count, on serum follicle stimulating hormone, luteinizing hormone, plasma testosterone and outcome in idiopathic oligospermic men. AB - Two hundred fifty subfertile men with idiopathic oligospermia (count less than 20 million/ml) were treated with mesterolone (100-150 mg/day) for 12 months. Seminal analysis were assayed 3 times and serum follicle stimulating hormone (FSH) luteinizing hormone (LH) and plasma testosterone were assayed once before treatment and repeated at 3, 6, 9 and 12 months after the initiation of treatment. One hundred ten patients (44%) had normal serum FSH, LH and plasma testosterone, 85 patients (34%) had low serum FSH, LH and low plasma testosterone. One hundred seventy-five patients (70%) had moderate oligospermia (count 5 to less than 20 million/ml) and 75 patients (30%) had severe oligospermia (count less than 5 million/ml). Seventy-five moderately oligospermic patients showed significant improvement in the sperm density, total sperm count and motility following mesterolone therapy whereas only 12% showed improvement in the severe oligospermic group. Mesterolone had no depressing effect on low or normal serum FSH and LH levels but had depressing effect on 25% if the levels were elevated. There was no significant adverse effect on testosterone levels or on liver function. One hundred fifteen (46%) pregnancies resulted following the treatment, 9 of 115 (7.8%) aborted and 2 (1.7%) had ectopic pregnancy. Mesterolone was found to be more useful in patients with a sperm count ranging between 5 and 20 million/ml. Those with severe oligospermia (count less than 5 million) do not seem to benefit from this therapy. PMID- 2892729 TI - Termination of second trimester pregnancy with laminaria and intramuscular 15 methyl PGF2 alpha or 16-phenoxy-omega-17,18,19,20-tetranor PGE2 methyl sulfonylamide. A randomized multicenter study. AB - The present study included 592 second trimester healthy informed patients admitted to the participating hospitals for termination of pregnancy. In each patient one medium size laminaria tent was introduced into the cervical canal. The laminaria was withdrawn 12 h later and the patients were randomly allocated to either intramuscular infections of 15-methyl-PGF2 alpha (Prostin 15M), 0.25 mg every second hour, or 16-phenoxy-omega-17,18,19,20-tetranor PGE2 methyl sulfonylamide (Nalodor), 0.5 mg every fourth hour. Both treatment schedules were equally effective. The success rate was 95.6% and 94.5% for the E and F analogs, respectively, within 24 h of prostaglandin treatment. The mean duration of prostaglandin treatment was for Nalodor 10.8 h and for Prostin 15M 11.3 h. The mean total dose given of the two analogs was 1.85 mg and 1.65 mg, respectively. With the E analog, the frequency of gastrointestinal side effects was significantly lower than with the F analog. With the former compound, 83.2% had no episodes of diarrhea and 58.9% no vomiting. The mean number of episodes of vomiting and diarrhea per patient was for the E analog 1.0 and 0.4, respectively. The corresponding figures for the F analog were 2.3 episodes of vomiting and 2.2 episodes of diarrhea per patient. Only in three patients (0.5%) cervical laceration was found. It may be concluded that intramuscular administration of either analog after pretreatment with laminaria would appear to be more effective than other methods presently in use for termination of second trimester pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892730 TI - Mesonephric adenocarcinoma of cervix: a case report. AB - Adenocarcinoma arising in the cervix are not common tumors and those arising from mesonephric remnants are extraordinarily rare. A case of mesonephric adenocarcinoma of cervix has been reported in a girl age 1.5 years. This tumor could be diagnosed on the basis of histological examination by criteria laid down by McGee et al. (J Obstet Gynecol 84: 358, 1962) especially on the basis of dilated ducts corresponding to the remnant of mesonephric duct. PMID- 2892731 TI - Acute glomerulonephritis during the third trimester of pregnancy. AB - We report a very rare case of acute poststreptococcal glomerulonephritis (PSGN) occurring in the eighth gestational month. The pregnancy succeeded despite initially severe nephrotic syndrome, and after delivery there was a complete recovery to normal renal function. Fetal prognosis was also good. The diagnosis of PSGN was made based on serological examinations and postpartum renal biopsy. Light and electron microscopic findings showed that the glomerular lesions were different from those of typical pre-eclampsia. PMID- 2892732 TI - Primary pulmonary hypertension in pregnancy. AB - Primary pulmonary hypertension (PPH) is an uncommon but serious disease. Most patients with PPH are young women and the disease is more serious and eventful in pregnant women. We have experienced a patient with PPH in pregnancy, who was delivered successfully but died suddenly on the 7th day after the delivery. We report the obstetric course and the clinical management for the delivery of the patient with PPH. PMID- 2892733 TI - Cytocidal effects of hematoporphyrin derivative and argon dye laser on human gynecologic tumor cells in vitro. AB - Antitumor effects of hematoporphyrin derivative (HpD) plus argon dye laser were examined using various human gynecologic tumor cells in vitro. Irradiation alone with argon dye laser showed no effect on the DNA synthesis of cells. Treatment of the cells with HpD inhibited the DNA synthesis depending on the concentration and the exposure time. Photoradiation by argon dye laser following treatment of the cells with HpD 40 micrograms/ml for 2 h killed more than 80% of cells when the cells were irradiated for more than 3 min. Prominent degenerative changes of the cytoplasm and the nucleus appeared within 1 h after photoradiation. These changes were confirmed by morphology and DNA histogram. There were no differences of sensitivity to photoradiation among the three histologically different kinds of cells lines used. PMID- 2892735 TI - Serial serum ferritin and other hematological parameters in normal Nigerian primigravidae. AB - Serial hematological indices using Coulter Counter and serum ferritin using radioimmunoassay techniques were determined in 20 healthy Nigerian primigravidae with hemoglobin genotype AA. PCV fell significantly (P less than 0.001) to a minimum value at 28 weeks that was 6% lower than the mean value at 8 weeks postpartum. PCV at 36 weeks was still significantly (P less than 0.001) lower than the post partum value. There was an insignificant but progressive increase in MCV values throughout pregnancy. Changes in MCH and MCHC were insignificant. Ferritin levels in both the non-pregnant and pregnant subjects were high and probably reflected the high iron content of Nigerian foods. Though the cord serum ferritin level was significantly higher (P less than 0.001) than maternal ferritin at delivery there was no significant correlation between the two. PMID- 2892734 TI - Maternal mortality in Indonesia and Egypt. AB - Twenty-three percent of deaths to women of reproductive age (15-49 years) in Bali, Indonesia and Menoufia, Egypt were due to maternal causes. Among the younger women, the percentage was even higher. In both areas complications of pregnancy and childbirth were a leading cause of death (the first cause in Bali, the second in Menoufia). In both sites, postpartum hemorrhage was the most common cause of maternal death. Relative to the United States, the number of maternal deaths per 100,000 live births was 20 times higher in Menoufia and 78 times higher in Bali. Families of women of reproductive age who died were interviewed about the conditions leading to death and other characteristics of the deceased. Completed histories were reviewed by a Medical Panel who were able to assign a cause of death in more than 90% of cases. Two-thirds of the maternal deaths occurred to women who were over 30 and/or who had 3 children--the usual targets of family planning programs. Other possible intervention strategies include antenatal outreach programs, training of traditional birth attendants, and better hospital management of obstetric emergencies. PMID- 2892736 TI - Multiple pregnancy in the Maltese population. AB - This study analyses the multiple birth statistics for the Maltese Islands since 1959. Hospital twin births delivering during the period of 1983-1985 are analysed for a number of variables. The incidence of multiple pregnancy for the Maltese Islands appears to have decreased slightly since 1959 with an overall rate of 10.21 per 1000 maternities. The ratio of dizygotic to monozygotic twinning was computed to be 1.64. Patients with multiple pregnancies are shown to be generally elderly and multiparous. The pregnancy outcome is more likely to be complicated by an operative delivery, while the infant is more likely to be premature and of low birth weight. The perinatal mortality rate for multiple pregnancies is markedly in excess of that for singleton births. PMID- 2892737 TI - Postpartum glycated hemoglobin A1c and glucose tolerance test in mothers of large babies. AB - An attempt to study macrosomia and carbohydrate metabolism was made by determination of glycated hemoglobin A1c and by the oral glucose tolerance test (OGTT) in early puerperium. We studied 76 women who gave birth to large babies greater than or equal to 4.5 kg, 74 women whose babies were 3-4 kg as controls, and 36 type II diabetics. The median of HbA1c concentration in the diabetics (8.06%) was significantly higher than in the controls (6.49%), and the large babies' mothers (6.48%), P less than 0.001. No significant difference was found between HbA1c or glucose intolerance in mothers of large babies and mothers with average size babies. HbA1c showed an association with glucose levels in the diabetics and controls, P less than 0.001, but not in the large baby group. Mothers of large babies were as old and obese as the diabetics. We speculate that the relationship of postpartum GTT, HbA1c and gestational diabetes is unwarranted. PMID- 2892738 TI - Who is the elderly primigravida in Nigeria? AB - A retrospective study of 792 primigravidae, divided into four age-groups, was made in order to detect which group showed features of the elderly primigravida. Adolescent primigravidae showed significantly highest incidences of pre eclampsia, anemia, premature labor and cephalopelvic disproportion. The 20-24 year age-group showed the least incidence of pregnancy and labor complications. The 25-29 year age-group showed significantly increased incidences of uterine fibroids, pre-eclampsia, post-term pregnancy, premature labor, slow labor, fetal distress, failed induction, vacuum and cesarean section deliveries, when compared with the 20-24 year age-group. Most of the complications in the 25-29 year age group were continued into 30-34 years. A woman 25 years and above in her first pregnancy in Nigeria should be termed "elderly primigravida". PMID- 2892739 TI - Effectiveness of indomethacin (indocid) suppositories as post-episiotomy analgesia. AB - A double-blind, randomised placebo-controlled study was carried out to assess the efficacy of indometacin suppositories as a post-episiotomy analgesic. Thirty patients received 2 X 100 mg indometacin suppositories, and 30 patients received placebo suppositories within 15 min of an episiotomy repair operation. Local infiltration of the episiotomy incision was performed using 20 ml of 0.5% lignocaine in every case. Subjective symptoms of pain were evaluated 15, 30, 60 and 90 min post-episiotomy repair. Average numbers of hours as lying in patients after delivery is 4 h. None of the patients who received indometacin complained of post-episiotomy pain; whereas the patients on placebo manifested varying degrees of pain. PMID- 2892740 TI - Ultrasonographic identification and measurement of the human fetal pancreas in utero. AB - One hundred seventy ultrasonographic examinations, done to identify and measure the fetal pancreas in utero, were performed on 78 women with regular menstrual cycle, at 20-41 weeks of gestation. The pancreas, which could be identified after 20 weeks of gestation was measured in 38.4% at 36-39 weeks and 80.0% at 20-23 weeks gestation. The length of the fetal pancreas from the head to tail (FP-L) correlated well with the gestational age (r = 0.90, P less than 0.001). The normal sonographic characteristics of the fetal pancreas are discussed. PMID- 2892741 TI - Shoulder dystocia: its incidence and associated risk factors. AB - A case-control study (73 cases, 146 controls) was conducted to evaluate maternal, obstetrical and fetal factors associated with shoulder dystocia. Several factors were identified that were associated with a higher incidence of shoulder dystocia. However, none of them accurately predict those deliveries that will be complicated by shoulder dystocia. Among the 73 shoulder dystocia cases there were no perinatal deaths and all birth-related injuries associated with shoulder dystocia were temporary except for two cases of mild muscular weakness among 12 brachial palsy cases. PMID- 2892742 TI - Effect of some recent analgesics on labor pain and maternal and fetal blood gases and pH. AB - This study attempts to determine the analgesic properties of nalbuphine, pentazocine and butorphanol during labor and their potential effects on maternal and fetal blood gases and pH. Butorphanol analgesia was superior to either nalbuphine or pentazocine in relieving labor pain. The studied analgesics caused significant maternal respiratory acidosis and fetal metabolic acidosis. These acidotic changes were most marked with pentazocine, moderate with nalbuphine and minimal with butorphanol. PMID- 2892743 TI - The development and use of a standard symphysial-fundal height growth curve in the prediction of small for gestational age neonates. AB - The symphysial-fundal height (SF) measurement has been routinely used in obstetrics, although its value in the prediction of small-for-gestational-age (SGA) infants remains controversial. A retrospective study was performed in order to assess the sensitivity and specificity of the SF distance and establish guidelines for its use. Local neonatal birthweight distribution and SF growth curves were developed. Eighty-six percent of 28 SGA infants demonstrated one measurement under--1 S.D. of the mean SF growth curve as did 36% of appropriate for gestational age (AGA) neonates. Seventy-five percent of SGA infants subsequently demonstrated a second measurement below--1 S.D. of the mean curve, 90% prior to 36 weeks. Only 16% of AGA exhibited such a SF growth pattern. A protocol for maximizing the use of this inexpensive and easily obtained parameter is proposed. PMID- 2892744 TI - A simple painless, dangerless and easily repeatable procedure for endometrium biopsy. AB - Endometrium biopsies are currently carried out with the Novak curette. The drawbacks of this procedure are well known. The use of a female, disposable, sterile, plastic urinary catheter is a useful, easy, painless, dangerless and repeatable alternative to obtain suitable endometrium samples for histopathologic diagnosis. Since a small endometrial cancer can be overlooked, selection of patients is obligate, but this holds also insofar as all methods of endometrium biopsy are concerned. Accordingly, the procedure is primarily suitable in cases of "dysfunctional" bleeding. PMID- 2892745 TI - Recurrent endometriosis following hysterectomy and oophorectomy: the role of residual ovarian fragments. AB - Seven women with recurrent endometriosis after definitive surgery were evaluated. Plasma estradiol, FSH and LH indicated that recurrence was stimulated by residual ovarian fragments in six and pseudopregnancy regimen in one. Surgical treatment in two women was followed in one by hypertrophy of another ovarian fragment and reactivation of endometriosis as demonstrated by serial endocrine and ultrasonographic studies. Three patients responded well to hormonal treatment; one required pelvic irradiation. We conclude that: (1) small ovarian fragments may hypertrophy under increased gonadrotropin stimulation, become functional and stimulate recurrence of endometriosis; (2) resection of one such fragment may be followed by reactivation of another. PMID- 2892746 TI - RNA 3' cleavage and polyadenylation in oocytes and unfertilized eggs of Xenopus laevis. AB - Xenopus laevis histone H4 and H1 genes were transcribed in vitro to generate artificial precursor mRNAs (pre-mRNAs). These pre-mRNAs were microinjected into oocytes, matured oocytes, and unfertilized eggs of Xenopus laevis and their 3' cleavage and polyadenylation were investigated. In the oocyte nucleus both H4 and H1 pre-mRNAs were 3' cleaved but were not detectably polyadenylated. In the oocyte cytoplasm there was neither 3' cleavage nor polyadenylation of these histone pre-mRNAs. When injected into either matured oocytes or unfertilized eggs, the pre-mRNAs underwent 3' cleavage but this was inefficient when compared to the oocyte nucleus. In addition approximately 50% of the remaining uncleaved pre-mRNA was subject to a polyadenylation activity which added A tails of approximately 70 A residues. In contrast, artificial mouse beta-globin pre-mRNAs were not detectably 3' cleaved or polyadenylated in either microinjected oocytes or unfertilized eggs. PMID- 2892747 TI - Characterization of neurotransmitter phenotype during neuronal differentiation of embryonal carcinoma cells. AB - Embryonal carcinoma cells are useful in the study of embryogenesis and development, and their differentiation into neurons serves as a model of neuronal development. Retinoic acid was used to differentiate P19S18O1A1 embryonal carcinoma cells into neuronal, glial, and fibroblast-like cells and the phenotype of the neuronal population was examined. Neuron-specific enolase was present in the neuronal cells, suggesting that these neurons had reached some degree of maturity. A population (approximately 70%) of the neurons showed positive immunocytochemistry for tyrosine hydroxylase, dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase, three enzymes in the pathway of catecholamine synthesis. Therefore a population of the neurons appeared to be adrenergic. These neurons also showed a low level of histofluorescence for endogenous catecholamines and exhibited an exogenous catecholamine reuptake system. In order to determine the phenotype of other neuron-like cells found to be negative for the adrenergic properties examined, immunocytochemistry for neuropeptides and neurotransmitters known to coexist within central neurons was performed. Serotonin, vasoactive intestinal peptide, glutamic acid decarboxylase, and choline acetyltransferase were all absent from retinoic acid-treated P19S18O1A1 neuronal cultures. These studies, along with those that compare the effects of retinoic acid and other growth modulators on neuronal differentiation of embryonal carcinoma cells, should aid in the understanding of neuronal induction and development in vivo. PMID- 2892748 TI - Haploid expression of the rooster protamine mRNA in the postmeiotic stages of spermatogenesis. AB - cDNA clones were prepared from poly(A)+ mRNA isolated from a population enriched in postmeiotic rooster testes spermatogenic cells. A series of clones was sequenced at random and two partial sequences corresponding to the C-terminal coding and 3' untranslated region of the chicken protamine mRNA were obtained. The deduced amino acid sequence of this C-terminal coding region corresponds to the sequence previously described at the protein level for the chicken protamine, galline [Nakano, M., Tobita, T., and Ando, T. (1976), Int. J. Peptide Prot. Res. 8, 565-578]. To study the expression of this protamine gene, RNA was prepared from chicken testes at different stages of development, electrophoresed in formaldehyde-agarose gels, transferred to a nylon membrane, and hybridized with a rooster protamine cDNA probe. Two populations of mRNA of sizes ranging between 420 and 465 bases are expressed in postmeiotic rooster testis cells. To determine if there was a differential expression of the two populations of mRNA in the final postmeiotic haploid stages of spermatogenesis, RNA was purified from adult rooster cells separated at unit gravity according to their differences in size by the Staput technique. The RNA was similarly analyzed by Northern blots. The results indicate that round spermatids are enriched in the 465-nucleotide mRNA species, whereas in the final stage of elongated spermatids the 420-nucleotide species is the only one present, suggesting either post-transcriptional processing, the presence of two different sets of genes that are differentially expressed, or a single set of genes with differential promoter usage. PMID- 2892749 TI - Coordinate accumulation of five transcripts in the primary mesenchyme during skeletogenesis in the sea urchin embryo. AB - The sea urchin larval skeleton is produced by the primary mesenchyme (PM), a group of 32 cells descended from the four micromeres of the 16-cell embryo. The development of this lineage proceeds normally in isolated cultures of micromeres. A complementary DNA (cDNA) library was generated from cytoplasmic polyadenylated RNA isolated from differentiated micromere cultures of Strongylocentrotus purpuratus. Five clones were selected on the basis of their enrichment in differentiated PM cell RNA as compared to the polyribosomal RNAs of other embryonic cell types and other developmental stages. Each cloned cDNA hybridized to a distinct RNA that was abundant in the polyribosomes of differentiated PM cells, but absent from larval ectoderm and from 16-cell embryos. These RNAs were encoded by single or low copy genes. In situ hybridization analysis of the most abundant of these RNAs (SpLM 18) demonstrated that it was specifically limited to the skeletogenic PM of intact embryos. During the development of the PM, all five RNAs exhibited the same schedule of accumulation, appearing de novo, or increasing abruptly just before PM ingression, and remaining at relatively high levels thereafter. This pattern of RNA accumulation closely paralleled the pattern of synthesis of PM-specific proteins in general (Harkey and Whiteley, 1983) and of the SpLM 18-encoded protein specifically (Leaf et al., 1987). These results indicate that at least five distinct genes in the sea urchin, each of which encodes a PM-enriched or PM-specific mRNA, are expressed with tight coordination during development of the larval skeleton. They also demonstrate that expression of these genes in the PM is regulated primarily at the level of RNA abundance rather than RNA utilization. PMID- 2892750 TI - Fetoacinar pancreatic protein in the developing human pancreas. AB - The distribution of the 110-kilodalton fetoacinar pancreatic (FAP) protein was examined in 56 pancreases obtained from human embryos and fetuses (ranging 6 from weeks of gestation to full term) and 10 normal adult pancreases. This recently discovered protein is a concanavalin-A-binding glycoprotein that is specific for acinar cells of the pancreas. Using a murine monoclonal antibody for either immunoperoxidase or immunofluorescence procedures, FAP-protein expression was not found in embryos at less than 9 weeks of gestation. At 9-10 weeks, a clear staining was observed in the terminal portions of dilated buds in primitive pancreatic tubular structures (i.e., the site of the first development of the future acinus). At 11-12 weeks, acinar structuration began, and FAP-protein expression increased as shown by the higher number of stained acini and the greater staining intensity. Maximal expression occurred at 15-22 weeks and then gradually decreased; from 28 to 32 weeks until full term, the pancreas was almost negative for this protein. In the adult pancreases, the protein was either absent or only present in acinar cells surrounding the islets of Langerhans. The pancreatic ducts and endocrine cells remained negative throughout gestation and in adults. FAP-protein thus appears to be a marker of acinar-cell differentiation. Its function remains unknown at present. Its close association with the growth and development of the pancreas together with the fact that, in a previous study, it was found to be re-expressed in pancreatitis and in cancer, suggest that it may play a role in developmental regenerative and neoplastic processes in the pancreas. PMID- 2892751 TI - The mouse Hox2.3 homeobox-containing gene: regulation in differentiating pluripotent stem cells and expression pattern in embryos. AB - Genomic and cDNA clones of the mouse Hox2.3 gene have been isolated. Expression of this gene was characterized in differentiating embryonal carcinoma (EC) and embryonic stem (ES) cells, and in the 13.5-day embryo. Hox2.3 is expressed at a very low level, if at all, in undifferentiated ES and EC cells. As previously reported for the Hox1.1 and Hox2.1 genes, differentiation of pluripotent stem cells induced by a nonchemical method is not accompanied by strong accumulation of Hox2.3 transcripts. Treatment of the stem cells with a chemical inducer like retinoic acid (RA), and also hexamethylenebisacetamide (HMBA), or 5-bromo-2' deoxyuridine (BUdR), simultaneously accelerates differentiation and stimulates accumulation of Hox2.3 mRNA to high levels. Addition of RA several days after the cells have been induced to differentiate by a nonchemical method induces Hox2.3 transcript accumulation as well. For comparison, expression of the En-1 gene, which contains a homeobox belonging to a different class from that of the Antennapedia-related Hox1.1, Hox2.1, and Hox2.3 genes, was analyzed. The En-1 gene was found also to be sensitive to this regulation by chemical inducers of differentiation. It was observed that treatment of undifferentiated EC cells with the inhibitor of protein synthesis cycloheximide resulted in slight accumulation of Hox2.3 mRNA, suggesting the involvement of a short-lived protein in keeping the level of homeobox-gene transcription low in EC cells. The highest level of Hox2.3 transcripts in 13.5-day embryos in vivo was observed in the spinal cord. Comparison with the expression pattern of three other homeobox genes revealed overlapping gradients of mRNA along the longitudinal brain-spinal-cord axis. An important question is that of the molecular basis for such a spatially restricted accumulation of homeobox transcripts. Hox2.3 is expressed at a much lower level in rat and mouse embryonic midbrain than in spinal cord in vivo. We have shown that addition of RA to primary cultures of cells from rat embryo mesencephalon leads to strong accumulation of Hox2.3 mRNA. A possible interpretation is that RA mimics one or more spatially restricted effectors, accounting for the local accumulation of Hox2.3 transcripts in the embryonic central nervous system. Control of Hox2.3 gene expression in vivo may obey some similar mechanisms as in chemically stimulated EC and ES cells in vitro. PMID- 2892752 TI - Circulatory effects of somatostatin analogue in two conscious rat models of portal hypertension. AB - A somatostatin analogue, a long-acting octapeptide (SMS 201-995), has been reported to decrease portal pressure, but the mechanism is unclear. To elucidate the effects of this drug on both systemic and splanchnic hemodynamics, it was administered in two conscious rat models of portal hypertension. The dose response curves showed that the somatostatin analogue significantly decreased portal pressure at a lower dose in rats with cirrhosis than in portal vein stenosed rats. Calculated ED50 values were significantly different among all groups. Intravenous infusion of 8 micrograms/kg body wt.h of somatostatin analogue significantly decreased cardiac output by approximately 20% in both groups of portal hypertensive rats and increased mean arterial pressure by 7%. Accordingly, systemic vascular resistance markedly increased, indicating vasoconstrictor effects of this drug. The somatostatin analogue also significantly decreased portal tributary blood flow by 18% in portal vein stenosed rats and 27% in cirrhotic rats. In sham-operated rats, somatostatin analogue had no effect on the systemic or splanchnic circulation. This study shows that somatostatin analogue decreases portal pressure principally by reducing portal tributary blood flow. This reduction may be due to either a direct vasoconstrictive effect or diminution in vasoactive hormone release. PMID- 2892753 TI - 5-Aminosalicylic acid protects against ischemia/reperfusion-induced gastric bleeding in the rat. AB - The aim of the present study was to determine whether the split products of sulfasalazine, sulfapyridine, and 5-aminosalicylic acid can ameliorate ischemia/reperfusion-induced injury to the gastric mucosa. Gastric mucosal damage was assessed by measuring (a) 51Cr-labeled red blood cell leakage into the gastric lumen, (b) the area of gross mucosal lesions, and (c) the extent of histologically demonstrable mucosal damage. In rats treated with 5-aminosalicylic acid, but not in those treated with sulfapyridine, the leakage of 51Cr-labeled red blood cells and the area of gross mucosal lesions after ischemia/reperfusion were significantly reduced as compared with untreated (control) rats. Inasmuch as 5-aminosalicylic acid (the therapeutic moiety of sulfasalazine) has been reported to be a hydroxyl radical scavenger, we also assessed the effects of dimethylsulfoxide (another hydroxyl radical scavenger) on ischemia/reperfusion induced gastric mucosal injury. In rats treated with dimethylsulfoxide, leakage of 51Cr-labeled red blood cells and the area of gross mucosal lesions after ischemia/reperfusion were significantly reduced as compared with control rats. The results of this study support the contention that ischemia/reperfusion induced gastric bleeding involves the hydroxyl radical and indicate that 5 aminosalicylic acid significantly attenuates this vascular injury. PMID- 2892754 TI - [Bone marrow preservation at positive temperatures]. PMID- 2892755 TI - Endocrine pancreas of Testudo graeca L. (Chelonia) in summer and winter: an immunocytochemical and ultrastructural study. AB - Insulin-, glucagon-, somatostatin-, and PP-immunoreactive cells were identified immunocytochemically using antisera raised against mammalian hormones in the pancreas of Testudo graeca in both winter and summer. The endocrine cells were present throughout the gland, forming scarce islets except in the splenic region. The insulin cell islets were larger and more numerous in the splenic region than in the duodenal one. Winter glucagon-immunoreactive cells were found mainly in isolation while the summer ones occurred in groups which showed no immunoreactive central area; in both seasons these cells were more numerous in the splenic region than in the duodenal one. Somatostatin-immunoreactive cells were found isolated or grouped together more frequently in the splenic region in the summer specimens. No PP-immunoreactive cells were found in the splenic region, although they were numerous and isolated in the duodenal zone. Four cell types (B, A, D, and PP cells) were ultrastructurally characterized by the shape, size, and electron density of their respective secretory granules. Certain ultrastructural differences were detected in the summer and winter endocrine pancreatic cells. In summer specimens a fifth cellular type was observed. The presence of B, D, and PP cells among the epithelial pancreatic duct cells may confirm the comparatively primitive organization of the T. graeca endocrine pancreas. PMID- 2892756 TI - The invected gene of Drosophila: sequence analysis and expression studies reveal a close kinship to the engrailed gene. AB - The invected and engrailed genes are juxtaposed in the Drosophila genome and are closely related in sequence and pattern of expression. The structure of the most abundant invected transcript was defined by obtaining the full-length cDNA sequence and by S1 nuclease sensitivity and primer extension studies; a partial sequence of the invected gene was determined; and the developmental profile of invected expression was characterized by Northern analysis and by in situ localization. The invected gene, like the engrailed gene, is expressed in the embryonic and larval cells of the posterior developmental compartments and in the embryonic hindgut, clypeolabrum, and nervous system. Like the engrailed gene, the invected gene can encode a protein of approximately 60 kD that contains a homeo box near its carboxyl terminus; indeed, a sequence of 117 amino acids in the carboxy-terminal region of both proteins is almost identical. The developmental role of the invected gene is not known. PMID- 2892757 TI - En-1 and En-2, two mouse genes with sequence homology to the Drosophila engrailed gene: expression during embryogenesis. AB - Two mouse genes, En-1 and En-2, have sequence homology to the engrailed (en) and invected (inv) genes of Drosophila (Joyner et al. 1985). Partial nucleotide sequence analyses of genomic and cDNA clones show that the homologous sequences can encode a stretch of 107 amino acids, including a centrally located, 60-amino acid homeo box. Within the homologous regions of the mouse and Drosophila genes, 78 (73%) of the amino acids are identical. Such extensive conservation of sequence outside the homeo box between vertebrate and Drosophila homeo box containing genes is thus far unique. En-1 and En-2 are expressed during mouse embryogenesis. Transcripts from both genes were detected in RNA samples from teratocarcinoma cells, which serve as in vitro models for the early embryo, and from embryos at 9.5 through 17.5 days of development. For each gene we observed a unique pattern of changes in the number and relative intensities of transcripts detectable during embryonic development. Transcripts from both genes are represented abundantly in RNA extracted from the posterior portion of the fetal brain, and are much less abundant in RNA from other fetal tissues, including the anterior portion of the brain and the spinal cord. The chromosome map positions of En-1 and En-2 were determined by recombinant inbred strain analyses. Unlike their Drosophila counterparts, they are unlinked: En-1 is in the central portion of the mouse chromosome 1 and En-2 is in the proximal portion of mouse chromosome 5. Both genes map in the vicinity of mutations that are known to cause abnormalities during development. PMID- 2892758 TI - Changing patterns of transcriptional and post-transcriptional control of liver specific gene expression during rat development. AB - Genes coding for unique or tissue-specific (differentiated) functions in the liver are induced at different times during development. It has generally been felt that transcriptional control represents the dominant mechanism for regulating expression of these genes. We have determined the relative transcription rates and mRNA steady-state levels for a series of genes specifically or preferentially expressed in rat liver and find examples of transcriptional control (albumin, alpha-fetoprotein, alpha 1-antitrypsin, tyrosine aminotransferase, transferrin, and cytochrome P450, TF-1) and post transcriptional control (alpha 1-acid glycoprotein, apolipoproteins A-1 and E, malic enzyme, and ATP citrate lyase), as well as "mixed" regulation (ligandin and cytochrome P450, R17). Examples have been identified in which the predominant mode for regulating expression of preferentially expressed genes changes from transcriptional to post-transcriptional at different stages of liver development and some members of multigene families (cytochrome P450s and apolipoprotein genes) also show independent and sometimes contrasting modes of regulation. Therefore, it appears that regulation of specific gene expression in the liver is a dynamic process, far more complex than heretofore suspected, and a much greater contribution of post-transcriptional regulation accounts for changes in expression of genes representing major functions of the liver. PMID- 2892759 TI - Molecular characterization of the zerknullt region of the Antennapedia gene complex in Drosophila. AB - zerknullt (zen) is unique among the 18 known homeo box genes in Drosophila since it is required for the differentiation of the dorsal-ventral pattern, and does not appear to be involved in the process of segmentation. Here we show that the zen region of the Antennapedia complex (ANT-C) consists of two closely linked homeo box genes, designated z1 and z2. The z1 and z2 transcription units show essentially identical patterns of expression during early development, which are consistent with the timing and sites of zen+ gene activity. The putative proteins encoded by z1 and z2 are highly divergent and are related only by virtue of homeo box homology. We have used P-element-mediated germ line transformation to show that z1 alone can provide zen+ gene function, suggesting that the z2 gene might be dispensable. The occurrence of closely linked homeo box genes that display similar patterns of expression is not unique to the zen locus. Such gene duplications might provide important clues to the evolution of the homeo box gene family in Drosophila and other organisms. PMID- 2892760 TI - The expression and regulation of Sex combs reduced protein in Drosophila embryos. AB - Homeotic genes are expressed in spatially precise patterns during Drosophila development to control segmental differentiation. The Sex combs reduced (Scr) gene of the Antennapedia gene complex is involved in the determination of the labial and prothoracic segments of the embryo. To study both the wild-type pattern of Scr expression and the regulatory relationships of Scr to other regulatory genes, an antibody probe that detects the Scr protein was prepared. We find that the Scr gene product is expressed in a dynamic pattern over the course of embryogenesis, beginning in the ectoderm in parasegment 2 while the germ band is elongated and extending to parasegment 3 during the completion of germ band shortening. The locations of Scr protein correlate well with the part of the embryo that are altered in Scr- mutants. After head involution occurs, Scr protein is also expressed in the ganglion corresponding to parasegment 2 of the ventral nervous system. The precise spatial expression of Scr is attained through regulation by both homeotic genes and segmentation genes. The lack of proper Antennapedia or Polycomb gene function causes ectopic Scr protein expression. Mutations in the segmentation genes fushi tarazu, hunchback, Kruppel, and giant alter the spatial pattern of Scr expression. PMID- 2892761 TI - Complementary patterns of even-skipped and fushi tarazu expression involve their differential regulation by a common set of segmentation genes in Drosophila. AB - We have examined the position-dependent expression of two segmentation genes that contain a homeo box, even-skipped (eve) and fushi tarazu (ftz). Products encoded by both genes accumulate in a series of seven transverse stripes along the anterior-posterior body axis of developing embryos. Double-staining experiments show that eve and ftz proteins accumulate in complementary sets of embryonic cells. A total of eight zygotically active segmentation genes are required for the establishment and refinement of the eve and ftz expression patterns during development. Mutations that affect one of the genes were always found to produce a reciprocal alteration in the other. These results suggest that the eve and ftz promoters independently "interpret" the same positional cues to give differential patterns of expression. We propose that a combination of segmentation gene products that activates the expression of eve represses the expression of ftz, and vice versa. This proposal is discussed in the context of a hierarchy of interactions among segmentation genes, whereby the gap genes establish asymmetric patterns of eve and ftz expression in blastoderm-stage embryos, and interactions with other pair-rule genes serve to refine further the complementarity of eve and ftz expression during gastrulation and germ band elongation. PMID- 2892763 TI - [Immunoregulatory T cell subsets in children with mumps meningitis]. PMID- 2892762 TI - A genomic clone containing the promoter for the gene encoding the human lysosomal enzyme, alpha-galactosidase A. AB - We have isolated and characterized a human genomic clone for a lysosomal enzyme gene. The start point of transcription was identified using primer extension of poly(A)+ mRNA. This genomic clone is specific for human alpha-galactosidase A, and it includes sequences for the promoter, complete signal peptide, first exon, and part of the first intron. Direct and inverted repeat elements of 10, 11, 16, 19, and 22 nucleotides (nt) flank the promoter site. A (GA)n repeat element of approx. 60 nt with strong homology to similar elements identified in several species is located upstream from the promoter. A GGGCGG site specific for DNA binding protein Sp1 is located near a CAAT box, and the CCGCCC inverted repeat of the Sp1 binding sequence is located by the TATA box. The sequence immediately flanking the ATG start codon of the human alpha-galactosidase A is highly homologous to sequences flanking the ATG start codons of the other human lysosomal hydrolases for which sequence information is available (beta glucocerebrosidase, cathepsin B, cathepsin D, and beta-hexosaminidase alpha chain), but not for any of the other 133 human signal peptides examined. Our analysis also reveals that conversion of the propeptide to the mature enzyme involves cleavage of a C-terminal rather than an N-terminal fragment. This information about the normal alpha-galactosidase A gene will be useful for comparison to data obtained from patients with Fabry disease, who are characterized by a deficiency of this enzyme. This is the first genomic clone described to date for any lysosomal enzyme, and it establishes a reference for future analyses of the molecular events that mediate the expression of this important class of enzymes. PMID- 2892764 TI - Death through injection of barbiturates. AB - The authors report two cases of lethal intoxication due to barbiturates in two male individuals, respectively 24 and 35 years old. They stress the comparatively rare mode of administration of such drugs in the absence of another party, i.e. the parenteral way. PMID- 2892765 TI - [Hemodynamic changes following somatostatin administration. An experimental study of splanchnic circulation]. PMID- 2892766 TI - [Studies on the mechanism of gamma-glutamyltranspeptidase elevation in serum- concerning its hydrophobic and hydrophilic forms]. PMID- 2892768 TI - Nizatidine in the short-term treatment of duodenal ulcer--an Italian Multicenter Study. AB - One hundred and seventy three patients suffering from duodenal ulcer, were selected for a double-blind, controlled and randomized parallel multicenter study, with interval endoscopic examinations. This study was undertaken to compare the efficacy and safety of nizatidine administered at a single dose (300 mg "nocte") versus ranitidine (300 mg "nocte") in the treatment of acute duodenal ulcer. One hundred and sixty five patients were found to meet every admission criterion and completed the study (86 on nizatidine and 79 on ranitidine). On admission to the study, both groups were seen to have been correctly selected and epidemiologically well-distributed as to history of duodenal ulcer, previous treatments and pre-study symptoms. The ulcer was considered healed when complete re-epithelialization had occurred in areas of ulcerated mucosa. Healing rates of duodenal ulcer proved to be globally similar in the two groups, both in the 4th week (nizatidine, 78%; ranitidine, 78%) and in the 8th week (nizatidine, 91%; ranitidine, 95%). After four weeks of treatment, 67% of the patients treated with nizatidine no longer had any symptoms, while 87% patients no longer suffered from day pain, and 91% had no nocturnal pain. As a result, intake of antacids quickly decreased during the first four weeks. A similar response was observed in the group receiving ranitidine. After administration at a single dose of 300 mg in the evening, nizatidine proved to be at least as effective and safe as 300 mg of ranitidine administered in the same way, with respect both to ulcer healing and symptom response. PMID- 2892767 TI - Cardiovascular characterization of the DA2 dopamine receptor agonist quinpirole in rats. AB - In normotensive anesthetized rats, 15-min IV infusions of quinpirole (2.5-40.0 micrograms/kg/min) produced dose-related, rapidly appearing, and long-lasting decreases in mean carotid artery BP and HR. Hemodynamically, the hypotensive effects of quinpirole (10.0 micrograms/kg/min) were due to a fall in total peripheral vascular resistance inasmuch as CO did not undergo significant changes. Mesenteric, hindquarter, and renal blood flows were, respectively, reduced, unchanged, and increased by quinpirole; thus, the renal vascular resistance fell more than either the total peripheral or hindquarter vascular resistance. Biochemically, the hypotensive effects of quinpirole were accompanied by a decrease in the plasma level of norepinephrine and plasma renin activity. The peak fall in blood pressure produced by quinpirole was not significantly modified by atenolol, idazoxan, ranitidine, SCH 23390 (DA1 dopamine receptor antagonist), enalapril, or SK&F 100273 (V1 vasopressin receptor antagonist), but was entirely blocked by S-sulpiride or removal of autonomic nerve drive to the cardiovascular system with chlorisondamine. The effect of quinpirole on systemic and regional vascular resistances was antagonized by S-sulpiride. Furthermore, SK&F 100273 prevented the fall in mesenteric flow produced by quinpirole. Intracerebroventricular injection of quinpirole (10.0 micrograms/kg over 2 min) in saline- or SK&F 100273-pretreated rats produced the same hypotensive effects as an identical IV dose of the compound. In pithed rats, quinpirole (10 micrograms/kg/min IV over 15 min) decreased pressor responses to electrical stimulation of spinal cord outflow without affecting those to exogenously injected angiotensin II, B-HT 920, cirazoline, norepinephrine, or 5 hydroxytryptamine. This inhibitory effect was antagonized by S-sulpiride. The bradycardia produced by quinpirole in intact rats was mediated by the autonomic nervous system inasmuch as it was slightly modified by bilateral vagotomy, partly reduced by atenolol, and entirely prevented by pithing even when the low HR of the last preparation had been raised by IV infusion of isoprenaline. Furthermore, S-sulpiride, but not SCH 23390 or idazoxan, antagonized this effect. In pithed rats, quinpirole similarly inhibited the tachycardic responses elicited by electrical stimulation of either the spinal cord outflow (preganglionic) or postganglionic cardioaccelerator nerve fibers. This effect of quinpirole was susceptible to S-sulpiride but not idazoxan blockade. Finally, in conscious spontaneously hypertensive rats (SHR) but not in normotensive rats, quinpirole (10 micrograms/kg/min IA over 15 min) lowered blood pressure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2892769 TI - Pancreatic hormones disappearance after total pancreatectomy in the duck: correlation between plasma glucagon and glucose. AB - The decline of 3 plasma pancreatic hormones, glucagon (G), insulin (I) and somatostatin (S) was studied in fasting ducks after total pancreatectomy. The results show that the decrease of plasma glucose is highly correlated with the disappearance of G, while no important variation of the G/I ratio occurs during the period of observations (80 minutes) the animal being kept fasted. No participation of pancreatic S in glucose metabolism could be detected, the origin of peripheral S in the fasting state seeming due to the intestine for about 50%. PMID- 2892770 TI - The antidiabetic action of somatostatin-28 as assessed by the artificial endocrine pancreas: greater potency than somatostatin-14. AB - In order to investigate the action of somatostatin-28 (SS-28) on the metabolic homeostasis of insulin-dependent diabetics, we compared its effects to those of somatostatin-14 (SS-14) in terms of insulin sparing, changes in dextrose demands, glucose fluctuations and behavior of growth hormone and glucagon secretion. Eight insulin-dependent subjects were connected to Artificial Endocrine Pancreas (Biostator) for 84 hours during which they received intravenous infusions of either SS-14, SS-28 or isotonic saline in a randomized order, after a steady state of metabolism had been achieved. Five of the patients received SS-28 100 micrograms/h and SS-14 250 micrograms/h for 10 hours and three of them SS-28, 50 micrograms/h and SS-14 250 micrograms/h for 12 hours. Identical doses of both peptides were administered as bolus infusions prior to the continuous ones. Under SS-28 100 micrograms/h and SS-14 250 micrograms/h patients required 13.5 +/- 2.3 and 14.5 +/- 1.9 U of insulin respectively vs 40 +/- 5.6 U under isotonic saline infusion (mean +/- SEM, P less than 0.005 and P less than 0.01). At the same period the apparatus delivered 15 times more dextrose under SS-28 and 20 times more under SS-14. The magnitude of glucose fluctuations diminished from 64.6 +/- 2.47 mg% without to 41.4 +/- 2 mg% under SS-14 (P less than 0.01) and 46 +/- 3.8 mg% under SS-28 (P less than 0.02). Similar changes were observed in the remaining three patients who received SS-28 in the dose of 50 micrograms/h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892771 TI - Propranolol for prophylaxis of bleeding in cirrhotic patients with large varices: a multicenter, randomized clinical trial. The Italian Multicenter Project for Propranolol in Prevention of Bleeding. AB - To assess if propranolol prevents the first bleeding in cirrhosis, we randomly assigned 174 patients with large varices to either propranolol in doses reducing the resting heart rate by 25% (85 patients) or to a placebo (oral vitamin K, 89 patients). Sixty-nine patients had alcoholic cirrhosis, 24 posthepatitis cirrhosis and 81 cryptogenic cirrhosis. At the time of inclusion, 75 patients (43%) had ascites and according to the Child-Pugh classification, 103 (59%) had Class A disease, 60 (34%) Class B and 11 (7%) Class C. We report here an interim analysis of the study when all patients had been followed for at least 1 year (mean follow-up = 22 months). At this time, the cumulative proportion of patients free of bleeding was 74% (both differences not significant), respectively. A retrospective analysis showed that the cumulative percentage of patients free of bleeding was significantly higher in the propranolol- than in the control-group in the subsets of patients without ascites or in Child-Pugh Class A: respectively, 87 vs. 64% (p = 0.023) and 88 vs. 64% (p = 0.01). No differences in bleeding incidence were found in patients with ascites or in Child-Pugh Class B or C. Propranolol treatment did not affect survival in any subgroup. Twenty-five patients had to be withdrawn from propranolol because of side effects (n = 23) or low compliance (n = 2). If confirmed on a longer follow-up, these results suggest that propranolol could prevent the first bleeding in patients with well compensated cirrhosis. PMID- 2892772 TI - Postnatal treatment of rats with adrenergic receptor agonists or antagonists influences differentiation of sexual behavior. AB - The aim of the study was to investigate the possible role of the adrenergic system in development and differentiation of neural centers controlling sexual behavior in adulthood. For this purpose normal and androgenized female rats were treated with the alpha 1-receptor antagonist prazosin, the alpha 2-receptor agonist clonidine, or the alpha 2-receptor antagonist yohimbine-HCl throughout the first week of life. In adulthood all animals were ovariectomized and, after appropriate hormone-priming, they were tested for the capacity to display female and male sexual behavior patterns. Alteration of adrenergic transmission during the critical postnatal period for sexual differentiation of neural centers resulted in significant changes in the capacity to express female lordosis behavior in adulthood. In nonandrogenized animals clonidine significantly reduced the capacity for lordosis behavior. In androgenized animals clonidine had the opposite effect; it attenuated the inhibitory effect of testosterone propionate (TP) on differentiation of lordosis behavior. Prazosin, which was without effect in nonandrogenized animals, also attenuated the inhibitory effect of TP on differentiation of lordosis behavior. Yohimbine was without effect in androgenized and nonandrogenized animals. There was no influence of any of the adrenergic drugs on differentiation of male sexual behavior. In conclusion, differentiation of lordosis behavior seems to be mediated or modulated via adrenergic transmission. The defeminizing effect of testosterone postnatally on the differentiation of lordosis behavior seems to be expressed via alpha 1 adrenergic transmission, and diminished adrenergic activity during the postnatal period seems to protect the developing brain against this effect of testosterone. PMID- 2892773 TI - Hyperthermic catatonia. PMID- 2892774 TI - Prevalence of the 281 (Gly----Glu) mutation in hepatoerythropoietic porphyria and porphyria cutanea tarda. AB - The prevalence of the 281 (Gly----Glu) mutation in hepatoerythropoietic porphyria (HEP) was investigated by the use of hybridization with a synthetic oligonucleotide probe. The mutation was found in HEP-affected members of two unrelated families from Spain, but was absent in two other patients from Italy and Portugal who also had HEP. Moreover, this mutation was not detected in 13 unrelated cases of familial (type II) porphyria cutanea tarda. PMID- 2892775 TI - Bgl II RFLPs in the COL1A2 gene in the Finnish population. A comment. PMID- 2892776 TI - A DNA polymorphism of an apoprotein gene associates with the hypertriglyceridaemia of primary gout. AB - Genomic hybridization analysis has been used to investigate allelic frequencies of the genes coding for the four major apoproteins of high density lipoprotein (HDL); apoproteins AI, AII, CII and CIII, in a group of Caucasian subjects with primary gout. An uncommon allelic variant of the apoprotein CIII gene (the S2 allele) was significantly more common among the patients with gout (9/48, 19%) than among normouricaemic controls who were either randomly selected (1/41, 2%, P = 0.03) or normotriglyceidaemic (0/33, 0%, P = 0.013). Approximately 46% (22/48) of the subjects with gout were hypertriglyceridaemic (with a serum triglyceride greater than 2.1 mmol/l). Of the 22 patients in this subgroup, 5 (23%) had the uncommon S1S2 genotype, which was also a significantly greater proportion than among the normotriglyceridaemic controls (P = 0.015). These data suggest that the hypertriglyceridaemia associated with primary gout may have a genetic basis. In contrast, we found no differences in the frequencies of restriction fragment length polymorphisms of the genes for apoproteins AI, AII and CII. PMID- 2892777 TI - The Duffy blood group is linked to the alpha-spectrin locus in a large pedigree with autosomal dominant inheritance of Charcot-Marie-Tooth disease type 1. AB - The alpha-spectrin locus (SPTA) on chromosome 1 maps to 1q22-q25 and alpha spectrin specific probes detect restriction fragment length polymorphisms (RFLPs) with the endonucleases MspI and PvuII. The Duffy blood group (FY) has been mapped to the 1p21-q23 region. We found positive linkage between the alpha-spectrin and the Duffy loci with a maximal Lod score of 3.81 at theta = 0.0 using the computer program MLINK. This indicates that both loci are very closely linked and probably localized to 1q22-q23. PMID- 2892778 TI - Genomic structure and evolution of the human pepsinogen A multigene family. AB - A human cosmid library was screened with a pepsinogen A (PGA) cDNA probe, yielding 18 clones with (parts of) one, two or three PGA genes. By aligning these cosmids a restriction map of a PGA gene quadruplet was obtained in which the four genes are arranged in a highly ordered fashion in a head-to-tail orientation. Using the length in kilobases of the large polymorphic EcoRI fragment of the PGA genes, this quadruplet can be described as 15.0-12.0-12.0-16.6. An AvaII polymorphism allowed us to identify the two PGA haplotypes of the individual whose DNA had been cloned in the cosmid library to be a gene triplet and a gene quadruplet. By comparing the restriction maps of the central 12.0 genes in these multiplets to those of the flanking 15.0 and 16.6 genes, we postulate that these central genes arose from unequal but homologous crossing over between two 15.0 16.6 gene pairs. This hypothesis provides for the creation of a variety of haplotypes by additional cross overs and mutations. Southern blots of family and population material supports the existance of at least five common PGA haplotypes, including a single-gene haplotype, giving rise to a large number of different EcoRI patterns. The single PGA gene is probably the reciprocal crossing over product. Comparison between the DNA and protein polymorphisms suggests further micro-heterogeneity in the different PGA haplotypes. PMID- 2892779 TI - Apolipoprotein gene cluster on chromosome 19. Definite localization of the APOC2 gene and the polymorphic Hpa I site associated with type III hyperlipoproteinemia. AB - Recently, using an APOE cDNA probe, we discovered an Hpa I restriction fragment length polymorphism (RFLP) that appeared to be strongly associated with the expression of type III hyperlipoproteinemia (Klasen et al. 1987). In the present report it is shown that the same Hpa I RFLP can be revealed with both the APOC1 and APOC2 cDNA probes. This enabled us to localize the polymorphic Hpa I site between the APOE and APOC1 genes and to localize the APOC2 gene approximately 22 kb 3' of the APOC1 pseudogene on chromosome 19. PMID- 2892780 TI - c-Ha-ras-1 alleles in bladder cancer, Wilms' tumour and malignant melanoma. AB - Polymorphism of the human c-Ha-ras-1 gene has been analysed in DNA from 168 individuals using the enzymes MspI and HpaII. In all, 35 bladder cancer patients, 28 melanoma patients, 22 Wilms' tumour patients, 24 first-degree relatives of Wilms' tumour or melanoma patients and 59 unaffected controls were studied. A total of 13 different fragment sizes was detected, 4 "common" and 9 "unusual". Of the latter, 4 were observed only in cancer patients or their first-degree relatives. The frequency of unusual alleles was significantly greater in bladder cancer patients and in the combined tumour group than in controls, thus providing support for the association of unique Ha-ras alleles and cancer. Some unaffected relatives of patients carried unusual alleles, and thus there is no absolute relationship between Ha-ras genotype and disease. PMID- 2892783 TI - Linkage of the DNA-segment D7S13 (pB79a) with the cystic fibrosis locus. AB - A map distance of 2.9 cM between D7S13 (pB79a) and the cystic fibrosis (CF) locus was obtained from the analysis of 13 informative families with a history of CF. This result is based solely on the HindIII restriction fragment length polymorphism (HindIII-RFLP) at D7S13, since the interpretation of the MspI-RFLP at this locus was found to be unreliable. PMID- 2892782 TI - The use of DNA probes to establish parental origin in Down syndrome. AB - Molecular analysis was performed to determine the parental origin of the extra number 21 chromosome in 20 couples following the birth of a child with standard trisomy 21. The parent of origin was successfully identified in 9 of 20 (45%) using five chromosome-21-specific DNA probes and eight restriction endonucleases by restriction fragment length polymorphism and dosage analysis; seven were of maternal and two of paternal origin. Utilizing the observed allele frequencies, the expected frequencies of informative homozygous matings [2(p2q2)] approximate 10% for seven of eight enzyme/probe combinations; the eighth, TaqI/pPW231F (D21S3), is 3%. The observed phenotype frequencies for all enzyme/probe combinations tested conform closely to predictions by the Hardy-Weinberg law. Strong linkage disequilibrium was observed between the DNA markers of EcoRI and TaqI with probe pPW236B; identical results were obtained with G-95 alpha 1-11a. We were able to demonstrate that although these two probes are of different size, and hence not identical, they detect the same TaqI and EcoRI polymorphisms; therefore both should be assigned to a single locus, D21S11. PMID- 2892781 TI - Localization of the villin gene on human chromosome 2q35-q36 and on mouse chromosome 1. AB - A partial cDNA clone coding for the 110 carboxyterminal amino acids of human villin was used for mapping the human villin gene. In situ hybridization experiments on human chromosomes with tritiated probe allowed the regional localization of the villin locus to chromosome 2 at q35-36. Data obtained from restriction fragment length polymorphism analysis of two mouse species demonstrated the assignment of the villin gene to mouse chromosome 1 by assessment of linkage with the fast skeletal isoform of the myosin light-chain gene. These villin gene localizations add a fourth locus to the conserved gene cluster encoding the fast skeletal muscle isoform of the myosin light chain, isocitrate dehydrogenase, and the gamma crystallins and confirm the partial homology of the human chromosome 2 long arm and mouse chromosome 1. PMID- 2892784 TI - Analysis of crossover type in the alpha -3.7 haplotype among sickle cell anemia patients from various parts of Africa. AB - The frequency of alpha+-thalassemia has been determined in African populations carrying beta S-chromosomes of different origins. All these alpha+ thalassemias result from a right-ward deletion. Restriction mapping of the alpha 3.7/haplotype with the enzyme ApaI only showed the presence of a type I crossover. RsaI polymorphism at the 5' end of Z alpha 2 is largely represented in the normal population (gene frequency 23%) but, in our series, never associated with the alpha -3.7/haplotype. PMID- 2892785 TI - Identification of lymphoid cell lines bearing receptors for somatostatin. AB - The MT-2, derived from an adult T-cell leukaemia (ATL) cell, the Molt-4F, a human T-cell line, and the Isk, an EB virus-transformed B-cell line, were found to have high-affinity receptors for somatostatin, a cyclic tetradecapeptide that inhibits the release of substances such as growth hormone, TSH, glucagon, insulin, secretin, gastrin and cholecystokinin. The quantity of radioactivity bound varied linearly with the number of cells, and was displaced by non-radioactive somatostatin in a concentration-dependent manner. Specific binding of 125I somatostatin was time- and temperature-dependent and at 22 degrees reached equilibrium within 120 min. Scatchard analysis demonstrated one class of specific binding sites on MT-2 cells, Isk cells and Molt-4F cells that had respective densities and dissociation constants of 109 pM and 0.64 nM, 102 pM and 1.1 nM, and 5.8 pM and 0.22 nM. PMID- 2892786 TI - Myc-1 is centromeric to the linkage group Ly-6--Sis--Gdc-1 on mouse chromosome 15. AB - A survey of wild mouse DNA with a c-myc exon 1 probe revealed a Taq I restriction fragment length polymorphism (RFLP) among Mus species. As a result of this Taq I RFLP, a cross between Mus musculus domesticus and BALB/cJ permitted the positioning of Myc-1 on chromosome 15 with respect to Ly-6, Sis, and Gdc-1. Compilation of the recombination frequency generated from this cross with published cytogenetic and plasma-cytoma somatic cell hybrid data suggests the following chromosome 15 orientation: centromere--Myc-1--Ly-6--Sis--Gdc-1- telomere. This gene order is consistent with conservation of man-mouse synteny. PMID- 2892788 TI - Absence of HTLV-1 infection in India--a preliminary report. PMID- 2892787 TI - Bgl II restriction fragment length polymorphism of human complement C4A gene coincides with BF*F allele of factor B. PMID- 2892789 TI - Effect of some beta-adrenoceptor antagonists on cerebrocortical acetylcholine release in rats. PMID- 2892790 TI - Relative larvivorous potentials of some local fishes against vector mosquito larvae. PMID- 2892791 TI - Effect of beta-adrenoceptor blocking agents on isolation and apomorphine-induced aggression in rodents. PMID- 2892792 TI - Frequency of fimbriation of nontypable Haemophilus influenzae and its ability to adhere to chinchilla and human respiratory epithelium. AB - To date, we have examined nearly 60 clinical isolates of nontypable Haemophilus influenzae (26 nasopharyngeal, 33 from middle ear effusions) and have found that 100% were fimbriated. The percentage of cells bearing fimbriae within each isolate varied from less than 10 to 100%, with fimbriae being either peritrichous or bipolar in distribution. Fimbriae were approximately 2.4 to 3.6 nm in width; however, there was a high degree of variability in both length and number of fimbriae per individual bacterial cell among these isolates. All isolates tested adhered to both human oropharyngeal cells and chinchilla tracheal epithelium regardless of the degree to which the particular isolate was fimbriate. The level or degree of fimbriation did not correlate with either site of isolation, biotype, strength of hemagglutination reaction, or type of effusion present in the ear. These appendages appear to be quite different from those described for type b H. influenzae in which the ability to adhere and strength of ability to hemagglutinate correlated strongly with degree of fimbriation. PMID- 2892793 TI - Aerobactin and other virulence factor genes among strains of Escherichia coli causing urosepsis: association with patient characteristics. AB - To assess the role of aerobactin as a virulence factor among uropathogenic Escherichia coli, we determined the prevalence, location, and phenotypic expression of aerobactin determinants among 58 E. coli strains causing bacteremic urinary tract infections. We correlated the presence of the aerobactin system with antimicrobial-agent resistance, the presence and phenotypic expression of other uropathogenic virulence factor determinants (P fimbriae, hemolysin, and type 1 fimbriae), and characteristics of patients. Colony and Southern hybridization of total and plasmid DNA with DNA probes for each virulence factor showed that aerobactin determinants were present in 78% of the strains and were plasmid associated in 21%, whereas P fimbria, hemolysin, and type 1 fimbria determinants were present in 74, 43, and 98% of the strains, respectively, and were always chromosomal. Chromosomal aerobactin, P fimbria, and hemolysin determinants occurred together on the chromosome more often in strains from patients without predisposing urological or medical conditions (P = 0.04). Strains with plasmid-encoded aerobactin lacked determinants for P fimbriae (P = 0.004) and hemolysin (P = 0.0004), were resistant to multiple antimicrobial agents (P = 0.0001), and were found only in compromised patients. Mating experiments demonstrated that some aerobactin plasmids also encoded antimicrobial agent resistance. These findings suggest that the determinants for aerobactin, P fimbriae, and hemolysin are conserved on the chromosome of the antimicrobial agent-susceptible uropathogenic strains of E. coli which invade noncompromised patients. In contrast, these chromosomal virulence factors are often absent from E. coli strains causing urosepsis in compromised hosts; these strains may acquire plasmid aerobactin in conjunction with antimicrobial-agent resistance genes. PMID- 2892794 TI - Human salivary acidic proline-rich proteins and statherin promote the attachment of Actinomyces viscosus LY7 to apatitic surfaces. AB - Actinomyces viscosus LY7 cells adsorbed in high numbers to experimental pellicles formed on hydroxyapatite (HA) from human parotid or submandibular saliva but not to pellicles prepared from human plasma or serum. To determine the nature of the salivary components responsible for promoting adhesion, pellicles were prepared from fractions of submandibular and parotid saliva obtained by chromatography on Trisacryl GF 2000 columns. Adsorption of LY7 cells was promoted by two groups of fractions. Each group was rechromatographed on DEAE-agarose. Fractions which promoted adsorption of LY7 cells were found by polyacrylamide gel electrophoresis to contain the acidic proline-rich proteins (PRPs) and statherin. Pellicles prepared from 12-micrograms/ml solutions of pure PRP-1, PRP-2, or parotid isoelectric focusing (PIF-slow) variant promoted maximal adsorption of A. viscosus LY7 cells. Somewhat higher concentrations of PRP-3 and PRP-4 were required for maximal adsorption, indicating that the 44-residue carboxy-terminal segment of PRP-1, PRP-2, and PIF-slow enhances LY7 binding but is not essential. Much higher concentrations of statherin were required to promote LY7 adsorption. Adsorption of LY7 cells to pellicles prepared from PRP-1 was not affected over the range of pH 5 to 8. Adsorption was also not inhibited by 50 mM lactose, which is consistent with the notion that type 1 fimbriae, rather than type 2 fimbriae, were responsible. A. viscosus T14, Actinomyces odontolyticus ATCC 17982, and Actinomyces israelii 12597 also adsorbed to PRP-1 pellicles, whereas Actinomyces naeslundii ATCC 12104 did not. Although A. viscosus cells bind strongly to adsorbed PRP-1, the presence of PRP-1 or PRP-3 in solution did not inhibit adhesion. Similarly, [3H]PRP-1 did not bind to LY7 cells, nor was it degraded when incubated with the organism. However, LY7 cells adsorbed to [3H]PRP-1 pellicles. These data suggest that hidden molecular segments of PRP become exposed when the protein adsorbs to HA; these segments then react with adhesins of LY7 cells. The apparent ability of A. viscosus cells to recognize segments of PRPs which are exposed only in surface-adsorbed molecules provides a novel mechanism which enables the organism to attach to teeth when suspended in salivary secretions. PMID- 2892796 TI - A comparison of the adherence of fimbriated and nonfimbriated Haemophilus influenzae type b to human adenoids in organ culture. AB - Adherence of fimbriated and nonfimbriated variants of a single strain of Haemophilus influenzae type b to organ cultures of human adenoidal tissue was measured by three assays, two of which were quantitative. In one assay, the adherence of radioactively labeled bacteria was measured; the numbers of CFU of bacteria per gram of adenoidal tissue were 16.0 +/- 6.7 for fimbriated bacteria and 10.2 +/- 4.0 for nonfimbriated bacteria (P less than 0.05). In the second assay, adherent CFU were determined directly; the results were 23.4 +/- 17.2 CFU/g of tissue for fimbriated bacteria and 5.1 +/- 2.2 CFU/g for the nonfimbriated variant (P less than 0.02). By combining data from the two assays it appears that fimbriated and nonfimbriated bacteria do not compete for the same site on the tissue, and that the adherent bacteria do not change their state of fimbriation under the assay conditions used. In contrast, the third assay, scanning electron microscopy, showed very poor adherence of nonfimbriated bacteria. Fimbriated bacteria, on the other hand, adhered in clusters to nonciliated epithelial cells. Overall, the data indicate that fimbriae enhance adherence of H. influenzae type b to a type of tissue that is a normal site of human colonization and that nonfimbriated bacteria adhere by a distinctly different mechanism. PMID- 2892795 TI - The Mycobacterium tuberculosis 65-kilodalton antigen is a heat shock protein which corresponds to common antigen and to the Escherichia coli GroEL protein. AB - Monoclonal hybridoma antibodies directed against a 65-kilodalton (kDa) mycobacterial protein could detect similarly sized antigens in many other bacterial species. In Pseudomonas aeruginosa, the cross-reacting protein corresponded to a 62-kDa antigen that has been called Common Antigen. The mycobacterial 65-kDa antigen and Common Antigen are similar in that both (i) are highly immunoreactive molecules, (ii) contain species-specific and genus-specific epitopes in addition to the broadly cross-reactive epitopes, (iii) can be isolated as homomultimers of greater than 240 kDa, and (iv) have similar amino acid compositions. In Escherichia coli, the cross-reactive protein corresponded to the GroEL protein. Both the GroEL protein and the mycobacterial 65-kDa protein are expressed as heat shock proteins. PMID- 2892797 TI - A block of urovirulence genes encoding multiple fimbriae and hemolysin in Escherichia coli O4:K12:H-. AB - Cosmid gene libraries were constructed from a uropathogenic isolate of Escherichia coli O4:K12:H- that secretes alpha-hemolysin and produces the F14, F12-rel, F1C, and F13 fimbrial antigens. A series of overlapping clones was generated, and individual cosmid clones were found to express various combinations of fimbriae and hemolysin, suggesting that the genes for these potential virulence factors are closely linked. By using Southern hybridization analysis and restriction endonuclease mapping, it was demonstrated that the cosmid clones carried a nested set of overlapping, cloned, genomic DNA fragments. A comparison of the phenotypic properties of individual cosmid clones and subclones allowed the order of the gene clusters encoding these factors to be deduced. The cloning also revealed the presence of a fifth fimbria that had P adhesin specificity. PMID- 2892798 TI - Haemophilus influenzae serotype a: outer membrane protein classification and correlation with DNA polymorphism at the cap locus. AB - Fifty-four temporally and geographically distinct isolates of Haemophilus influenzae serotype a were characterized by (i) outer membrane protein composition and (ii) DNA polymorphism at the cap locus. In 53 of 54 cases, knowledge of the outer membrane protein type was accurately predictive of the cap locus polymorphism, suggesting that the majority of H. influenzae (type a) isolates have evolved from a limited number of clones. PMID- 2892799 TI - Effect of Bordetella pertussis adjuvant on parasite-specific IgE response in Paragonimus ohirai-infected rats. AB - Parasite-specific IgE response in rats infected with metacercariae of the lung fluke, Paragonimus ohirai, was enhanced about 8 times by Bordetella pertussis adjuvant. In rats infected by intraperitoneal transplantation of adult worms, the adjuvant markedly increased the usually low or absent parasite-specific IgE response. The most effective time of the adjuvant administration was different between the two modes of infections. PMID- 2892800 TI - Treatment with hCG increases the size of Leydig cells and testicular macrophages in unilaterally cryptorchid rats. AB - Adult, unilaterally cryptorchid rats were treated with a single injection of 200 i.u. human chorionic gonadotrophin (hCG). The morphological response of Leydig cells and testicular macrophages at 24 and 72 h after treatment was quantified using morphometry. Treatment with hCG induced an increase in the volume density of Leydig cells and macrophages, as well as in the average cell profile area of individual Leydig cells and macrophages in both scrotal and abdominal testes. However, the relative response was considerably larger in abdominal than in scrotal testes, and there was a strong positive correlation between the response of Leydig cells and macrophages. It is suggested that hCG, probably via effects on Leydig cells, also influences the function of testicular macrophages. PMID- 2892801 TI - Intratesticular steroids and gonadotrophin receptor concentrations in the testes of immature unilaterally cryptorchid rats. AB - Testicular descent was prevented unilaterally in newborn rats. In this experimental model of cryptorchidism the first morphological changes are noted in the abdominal testis at 16 days of age. Testicular weight was increased in the abdominal testis at 16 days of age, was unaffected at 20 days but was decreased at 30 days of age. The concentrations of LH and FSH receptors, and the hCG stimulated progesterone and testosterone secretion in vivo were analysed in scrotal and abdominal testes at different ages. LH- and FSH-receptor content per testis were unaffected by cryptorchidism at 12, 16 and 20 days of age but were depressed markedly at 30 days of age. At 20 days of age (but not earlier) hCG stimulated progesterone was reduced while testosterone secretion remained unchanged. It is concluded that the early functional changes in abdominal testes are not related to changes in gonadotrophin receptor content. PMID- 2892802 TI - The action of relaxin, fenoterol and etilefrine on uterine motility of the rat. AB - In uterine motility tests in virgin rats, the inhibitory action of the peptide hormone relaxin has been compared with the actions of fenoterol and etilefrine. At molecular levels, relaxin and fenoterol showed similar uterine inhibitory activity. Etilefrine was markedly less effective in inducing uterine relaxation. By pretreatment with propranolol, the inhibitory action of both fenoterol and etilefrine could be prevented but not the tocolytic effect of relaxin. Etilefrine, in higher doses, developed alpha-receptor activity as demonstrated by resumed uterine contractions. The doses required to induce beta 2- and alpha activities differed by a factor of approximately 4,000. PMID- 2892803 TI - Alterations of beta-adrenergic, muscarinic cholinergic receptors and imipramine binding sites in human lung tumors. AB - Direct ligand binding techniques have been used to compare beta-adrenergic receptors, muscarinic cholinergic receptors and imipramine binding sites in human tumoral and healthy lungs removed from eleven patients during operations. Beta adrenergic and muscarinic cholinergic receptors are present in tumoral tissues but their concentrations were decreased compared to healthy tissues. Imipramine binding sites were absent. It is concluded that this type of studies could bring additional information to morbid anatomy analysis and be used to follow illness evolution. PMID- 2892804 TI - Influence of adrenergic agonists and antagonists on lymphokine secretion in vitro. AB - Spleen cells of mice and lymph node lymphocytes of rats were cultured with epinephrine, norepinephrine and alpha- and beta-adrenergic drugs to determine effects on lymphokine secretion. After an incubation of 4.5 h it was found that the naturally occurring catecholamines and adrenergic drugs (isoprenaline, orciprenaline, terbutaline, norfenephrine, phenylephrine, clonidine, dobutamine) could induce the secretion of charge-changing lymphokines and lymphokines that stimulate the migration of lymphocytes. The beta-blocker propranolol inhibited the lymphokine secretion evoked by epinephrine and by beta-adrenergic agonists, whereas the alpha-blocker phentolamine antagonized the effects elicited by alpha adrenergic drugs. Phenylethylamine also induced a significant secretion of lymphokines. Two non-phenylethylamines had no effect. The stimulatory capacity of adrenergic agonists, the inhibitory activity of the appropriate antagonists and the comparison with two non-phenylethylamines support the hypothesis on specific influence of catecholamines on the lymphocyte function. PMID- 2892805 TI - Reduction of suppressor cell activities of human peripheral blood lymphocytes by a streptococcal preparation, OK-432. AB - The effect of a streptococcal preparation, OK-432 on suppressor cell activities of peripheral blood lymphocytes was investigated. Suppressor cell activities were significantly reduced when they were generated in vitro by concanavalin A (Con A) in the presence of OK-432. However, the reduction of suppressor cell activities was not observed when OK-432 was added in the effector phase. Similarly, a significant reduction of prostaglandin E2 (PGE2)-induced suppressor cell activities by OK-432 was observed. No increases of either T-cells with Fc receptors for IgG or OKT8 reactive T-cells were observed after Con A stimulation in the presence of OK-432. The suppressive effect of the soluble suppressor factors (SSF) was not abrogated by OK-432 and the release of SSF from cells activated by Con A was not found in the presence of OK-432. Thus, it is suggested that OK-432 might interfere with the induction of suppressor cells, but not with the expression of their activities. PMID- 2892808 TI - Conformational study of a somatostatin analogue by high-field n.m.r. spectroscopy, in aqueous solution. AB - The cyclic analogue of somatostatin (SRIF), D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Thr NH2 (CTC), exhibits good affinity for both opioid and SRIF receptor systems. Its conformational properties were examined in water by high-field proton n.m.r. spectroscopy and compared with results previously obtained with structurally related analogues SMS 201-995 and Sandoz 204-090 in the same solvent. The assignments were made using 2 D-n.m.r. methods, especially long-range connectivities between neighbouring alpha protons, and between beta and aromatic protons. The 3JNH-C alpha H and delta delta/delta T values are compatible with an equilibrium between two gamma turns involving residues 2, 3 and 4 and residues 3, 4, and 5, respectively. PMID- 2892806 TI - Acrivastine versus clemastine in the treatment of chronic idiopathic urticaria. A double-blind, placebo-controlled study. PMID- 2892807 TI - Thermogenic effect of the new beta-adrenoreceptor agonist Ro 16-8714 in healthy male volunteers. AB - Previous investigations in experimental animals have shown that a new type of beta-adrenoceptor agonist (Ro 16-8714) possesses both thermogenic and antihyperglycemic properties. The aim of the study was to assess the thermogenic capacity of the compound in man after acute administration. Following an overnight fast three different doses (5, 10 and 20 mg) and a placebo were given per os to six normal-weight young men. The rate of energy expenditure (EE) and substrate utilization were determined by indirect calorimetry (hood system) before and for 6 h following the drug administration. Heart rate and blood pressure as well as plasma glucose, insulin and free fatty acid (FFA) concentrations were also measured at regular intervals throughout the study. The increment relative to base-line (mean +/- s.e.m.) in EE with placebo, 5, 10 and 20 mg was 4 +/- 3, 10 +/- 2, 11 +/- 2 and 21 +/- 2 percent respectively whereas heart rate was enhanced by 2 +/- 2, 8 +/- 3, 22 +/- 2, and 49 +/- 8 percent. Systolic blood pressure increased less (1 +/- 2, 8 +/- 1, 11 +/- 1 and 13 +/- 2 percent), and diastolic blood pressure did not change significantly. Simultaneously we observed a slight and transient increase in blood glucose, insulin and FFA concentrations. It is concluded that in lean individuals Ro 16 8714 is a potent thermogenic agent; however, new beta-adrenoceptor agonists should be developed in order to avoid the tachycardia associated with the thermogenic effect. PMID- 2892810 TI - [Drug therapy of stable angina pectoris]. PMID- 2892809 TI - Radiation therapy of spontaneous autoimmunity: a review of mouse models. AB - The classical types of generalized autoimmune disease in man are systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Several murine strains which develop SLE and sometimes RA-like diseases are now available. They should help in the understanding of the etiopathology of SLE and RA. Basically two main therapeutic strategies which use solely irradiation have been tried; one being sublethal whole-body irradiation (WBI) and the other fractionated total lymphoid irradiation (TLI). Other protocols which combine lethal WBI and stem cell transplantation have often been attempted. It was regularly found that the bone marrow transplant (BMT) dictates the immune status of the recipient. This paper reviews the data published about NZB, NZB/W, BXSB and MRL mice in this context. PMID- 2892811 TI - The cytoskeleton of the cultured human trabecular cell. Characterization and drug responses. AB - To determine the organization of the three major cytoskeletal elements of cultured human trabecular meshwork cells (actin filaments, microtubules and intermediate filaments), we employed fluorescence microscopy and stereo transmission electron microscopy of extracted, S-1 labeled and critical-point dried cells. Morphologic changes resulting from treatment with cytochalasin B, colchicine, taxol and nocodozole were also characterized. Compared with the cynomolgus monkey trabecular cell, morphologic differences in overall cell shape and orientation of both actin filaments and microtubules were noted. However, the responses to cytoskeletal active drugs were quite similar. Taxol, nocodozole and colchicine had a marked effect on microtubule organization, while nocodozole and colchicine had a marked effect on vimentin filament organization. None of these drugs produced marked changes in human trabecular cell shape. In contrast, treatment with the anti-actin drug cytochalasin B resulted in both a marked change in cell shape associated with organizational changes in all three cytoskeletal elements. These studies suggest a central role of actin filaments in determining overall cell shape and cytoskeletal organization in the cultured human trabecular cell. PMID- 2892812 TI - Somatostatin immunoreactivity in the cat adrenal medulla. Localization and characterization. AB - Somatostatin-like immunoreactivity was detected within the adrenal gland of the cat using specific monoclonal antibodies. Immunohistochemical studies demonstrated a few somatostatin-immunoreactive nerve fibers within the adrenal medulla. In addition, a large population of chromaffin cells in the cat adrenal medulla displayed intense somatostatin-like immunoreactivity. Similar cells were not observed in rat or guinea pig adrenal glands, although they were found in human material. The somatostatin-positive cells in the cat adrenal medulla often possessed short immunoreactive processes similar to those seen in somatostatin immunoreactive paracrine cells of the gut. Characterization of the somatostatin like immunoreactivity of the cat adrenal by high performance liquid chromatography and radioimmunoassay indicated that somatostatin-28 may account for over 90% of the observed immunoreactivity. It is suggested that somatostatin 28 may have a paracrine or endocrine role in the feline adrenal medulla. PMID- 2892813 TI - The internal mammary artery: coronary bypass conduit of choice. PMID- 2892814 TI - The experience of a lifetime. PMID- 2892815 TI - Authorization denied. Payment refused. PMID- 2892816 TI - A rare disorder. Primary esthesioneuroblastoma of the orbit. PMID- 2892817 TI - Tuberculous mastoiditis presenting with tuberculous meningitis. PMID- 2892819 TI - Hiring credentialed employees can lessen malpractice exposure. PMID- 2892818 TI - How safe is it? High dose intravenous methylprednisolone. PMID- 2892820 TI - Loss of genes on the short arm of chromosome 11 in human lung carcinomas. AB - Since loss of genes on the short arm of chromosome 11 (11p) is known to be closely associated with several human tumors, we analyzed DNA of lung carcinomas from 45 patients with respect to loss of heterozygosity at loci on 11p. We observed that loss of heterozygosity at 11p loci was quite frequent (17 of 41 informative cases, 41%) and it appeared that the loss might be associated with more advanced carcinomas than those of stage Ia. In many cases, sequences at the CAT and/or the D11S12-IGF2 loci were commonly deleted. These observations suggest that loss of genes at particular regions on 11p might be involved in progression of human lung carcinomas. PMID- 2892821 TI - Prevalence of antibodies to human T-cell leukemia/lymphoma virus type I and human immunodeficiency virus in Japanese immigrant colonies in Bolivia and Bolivian natives. AB - This study was performed to estimate human T-cell leukemia-lymphoma virus type-I (HTLV-I) infection and human immunodeficiency virus (HIV) infection in Japanese immigrant colonies in Bolivia, where no seroepidemiological study of HTLV-I or HIV has ever been reported, among 647 healthy adults and children of Japanese descent and Bolivian natives living in the same colonies. The overall prevalence of HTLV-I antibody was 12.6% (59/469) among Japanese immigrant populations, but increased with age, being 16.2% (49/303) among adults and 6.0% (10/166) among children; no significant difference in relation to sex was noted. The first generation immigrants (issei) from Kyushu, the large southwestern island of Japan where adult T-cell leukemia (ATL) is endemic, had 19.0% (49/258) HTLV-I seroprevalence, while issei from outside Kyushu had none (0/39). Among Bolivian members of the community, consisting mostly of Indians and persons of Spanish descent, the HTLV-I seroprevalence was 4.3% (7/164) overall, 2.4% (1/42) among adults and 4.9% (6/122) among children. No antibody to HIV was detected among Japanese or Bolivian populations. The results of this study show that: (1) there is a considerable number of HTLV-I carriers among Japanese immigrant populations in Bolivia, especially among immigrants from Kyushu, (2) there exist some HTLV-I carriers among Bolivian natives, raising the possibility of HTLV-I transmission by co-habitation with Japanese immigrants, (3) HIV is far from endemic in this district of Bolivia, at present. PMID- 2892822 TI - Effect of immunosuppressive factors produced by adult T cell leukemia cells on B cell responses. AB - The immunosuppressive activity of sera from adult T cell leukemia (ATL) patients and culture supernatants of ATL cells and ATL cell lines on B cell responses was examined in vitro. ATL sera and culture supernatants of ATL cells suppressed B cell proliferative and differentiative responses induced with B cell mitogens such as Staphylococcus aureus Cowan I and pokeweed mitogen. The suppressive effect was observed not only in the production of B cell growth factors (BCGF) and B cell differentiation factors (BCDF) by T cells, but also in the responsiveness of B cells to BCGF and BCDF. These results suggest that the immunosuppressive factors produced by ATL cells might act to suppress both the cellular immunity and the humoral immunity, and could have an important role in the induction of immunodeficient states in ATL patients. PMID- 2892823 TI - Detection of multidrug resistance markers, P-glycoprotein and mdr1 mRNA, in human leukemia cells. AB - We have examined the expression of P-glycoprotein in clinical leukemic cell samples by using a monoclonal antibody (MRK16) against P-glycoprotein. We found that leukemia cells isolated from 3 out of 6 patients with blast crisis of chronic myelogenous leukemia were reactive to MRK16. These 3 cell lines expressed high levels of mdr1 mRNA, which codes for P-glycoprotein. The present result indicates that the clinically refractory state of the tumor may be predicted in part by determining P-glycoprotein expression using the monoclonal antibody against P-glycoprotein, and the mdr1 probe. PMID- 2892824 TI - The gubernaculum during testicular descent in the human fetus. AB - This study of 178 male human fetuses and infants demonstrates that descent of the testis through the inguinal canal is a rapid process, with 75% of testes descending between 24 and 28 weeks of gestation. The gubernaculum is a cylindrical, gelatinous structure attached cranially to the testis and epididymis. While the testis is in the abdomen, the caudal tip of the gubernaculum is firmly attached to the region of the inguinal canal. In a few fetuses prior to descent the globular tip of the gubernaculum can be seen bulging through the external inguinal ring, covered by superficial fascia, with no macroscopically discernible extensions to the scrotum or any other area. Once the testis has passed through the inguinal canal, the bulbous lower tip of the gubernaculum is no longer firmly attached to any structure, nor does it extend to the bottom of the scrotum. Histologically the gubernaculum consists of undifferentiated mesenchymatous tissue. Prior to descent of the testis, there is an increase in the length of the intra-abdominal gubernaculum. The wet mass of the gubernaculum relative to the fetal mass increases rapidly prior to descent, while the relative wet mass of the testis remains constant during this period. There is also an increase in the wet/dry mass ratio of the gubernaculum, denoting an increase in its water content prior to descent. This indicates that a combination of growth processes is responsible for testicular descent, with the increase in the size of the gubernaculum playing the most important role in passage of the testis through the inguinal canal. PMID- 2892825 TI - Lithium responsive manic-like symptoms in two individuals with autism and mental retardation. PMID- 2892826 TI - Regulation of nitrogen assimilation in Saccharomyces cerevisiae: roles of the URE2 and GLN3 genes. AB - Mutations in the GLN3 gene prevented a normal increase in the NAD-glutamate dehydrogenase and glutamine synthetase levels in glutamate-grown Saccharomyces cerevisiae cells, whereas mutations in the URE2 gene resulted in high levels of these enzymes in glumate- and glutamine-grown cells. A ure2 gln3 double mutant had low levels of glutamate dehydrogenase and glutamine synthetase in cells grown on glutamate and glutamine; thus, gln3 mutations were epistatic to the ure2 mutations. The results suggest that the GLN3 product is capable of promoting increases in enzyme levels in the absence of a functional URE2 product and that the URE2 product antagonizes the GLN3 product. The URE2 and GLN3 genes were also found to regulate the level of arginase activity. This regulation is completely independent of the regulation of arginase by substrate induction. The activities of glutamate dehydrogenase, glutamine synthetase, and arginase were higher in cells grown on glutamate as the nitrogen source than they were in cells grown under a nitrogen-limiting condition. It had previously been shown that the levels of these enzymes can be increased by glutamine deprivation. We propose that the URE2-GLN3 system regulates enzyme synthesis, in response to glutamine and glutamate, to adjust the intracellular concentration of ammonia so as to maintain glutamine at the level required for optimal growth. PMID- 2892829 TI - Ammonium assimilation in Rhizobium phaseoli by the glutamine synthetase-glutamate synthase pathway. AB - Evidence from in vitro and in vivo studies showed that in Rhizobium phaseoli ammonium is assimilated by the glutamine synthetase (GS)-glutamate synthase NADPH pathway. No glutamate dehydrogenase activity was detected. R. phaseoli has two GS enzymes, as do other rhizobia. The two GS activities are regulated on the basis of the requirement for low (GSI) or high (GSII) ammonium assimilation. When the 2 oxoglutarate/glutamine ratio decreases, GSI is adenylylated. When GSI is inactivated, GSII is induced. However, induction of GSII activity varied depending on the rate of change of this ratio. GSII was inactivated after the addition of high ammonium concentrations, when the 2-oxoglutarate/glutamine ratio decreased rapidly. Ammonium inactivation resulted in alteration of the catalytic and physical properties of GSII. GSII inactivation was not relieved by shifting of the cultures to glutamate. After GSII inactivation, ammonium was excreted into the medium. Glutamate synthase activity was inhibited by some organic acids and repressed when cells were grown with glutamate as the nitrogen source. PMID- 2892828 TI - Purification and characterization of protease Re, a cytoplasmic endoprotease in Escherichia coli. AB - Protease Re, a new cytoplasmic endoprotease in Escherichia coli, was purified to homogeneity by conventional procedures, using [3H]casein as the substrate. The enzyme consists of a single polypeptide of 82,000 molecular weight. It is maximally active between pH 7 and 8.5 and is independent of ATP. It has a pI of 6.8 and a Km of 10.8 microM for casein. Since diisopropyl fluorophosphate and phenylmethylsulfonyl fluoride inhibited this enzyme, it appears to be a serine protease. Protease Re was sensitive to inhibition by L-1-tosylamido-2 phenylethylchloromethylketone but not to that by 1-chloro-3-tosylamido-7 aminoheptanone, thiol-blocking reagents, chelating agents, or various peptide aldehydes. Re also degraded [125I]globin, [125I]glucagon, and 125I-labeled denatured bovine serum albumin to acid-soluble products (generally oligopeptides of greater than 1,500 daltons), but it showed no activity against serum albumin, growth hormone, insulin, or a variety of fluorometric peptide substrates. It also hydrolyzed oxidatively inactivated glutamine synthetase (generated by ascorbate, oxygen, and iron) four- to fivefold more rapidly than the native protein. Protease Re appears to be identical to the proteolytic enzyme isolated by Roseman and Levine (J. Biol. Chem. 262:2101-2110, 1987) by its ability to degrade selectively oxidatively damaged glutamine synthetase in vivo. Its role in intracellular protein breakdown is uncertain. PMID- 2892827 TI - Characterization of the glutamyl-tRNA(Gln)-to-glutaminyl-tRNA(Gln) amidotransferase reaction of Bacillus subtilis. AB - In Bacillus subtilis, the formation of glutaminyl-tRNA is accomplished by first charging tRNA(Gln) with glutamate, which is then amidated. Glutamine was preferred over asparagine and ammonia as the amide donor in vitro. There is a functional analogy of this reaction to that catalyzed by glutamine synthetase. Homogeneous glutamine synthetase, from either B. subtilis or Escherichia coli, catalyzed the amidotransferase reaction but only about 3 to 5% as well as a partially purified preparation from B. subtilis. Several classes of glutamine synthetase mutants of B. subtilis, however, were unaltered in the amidotransferase reaction. In addition, there was no inhibition by inhibitors of either glutamine synthetase or other amidotransferases. A unique, rather labile activity seems to be required for this reaction. PMID- 2892831 TI - Obsessive-compulsive disorder: a treatment review. AB - Obsessive-compulsive disorder, which may affect 2% to 3% of the U.S. population, can be severely disabling, permeating an individual's personal, social, and work life. Only within the past 2 decades have effective treatments been proposed and tested. Specific behavior therapies such as exposure in vivo and response prevention have proved successful in decreasing compulsive rituals in 70% to 80% of patients who accept and comply with treatment. For those patients who do not respond to behavior therapy, medications should be used. To date the tricyclic clomipramine is the only medication that has been consistently effective in controlled studies. However, for certain patients other medications may be of benefit. For the minority of patients who do not respond to either behavior therapy or medication, psychosurgery--specifically stereotactic limbic leucotomy- should be considered a viable option. PMID- 2892830 TI - Introduction of the Escherichia coli gdhA gene into Rhizobium phaseoli: effect on nitrogen fixation. AB - Rhizobium phaseoli lacks glutamate dehydrogenase (GDH) and assimilates ammonium by the glutamine synthetase-glutamate synthase pathway. A strain of R. phaseoli harboring the Escherichia coli GDH structural gene (gdhA) was constructed. GDH activity was expressed in R. phaseoli in the free-living state and in symbiosis. Nodules with bacteroids that expressed GDH activity had severe impairment of nitrogen fixation. Also, R. phaseoli cells that lost GDH activity and assimilated ammonium by the glutamine synthetase-glutamate synthase pathway preferentially nodulated Phaseolus vulgaris. PMID- 2892832 TI - Effects of neuroleptics on body temperature. PMID- 2892833 TI - Inhibition of glucose-stimulated insulin release by alpha 2-adrenoceptor activation is parallelled by both a repolarization and a reduction in cytoplasmic free Ca2+ concentration. AB - Effects of the alpha 2-adrenergic agonist clonidine on insulin release, membrane potential, and cytoplasmic free Ca2+ concentration ([Ca2+]i) were investigated using pancreatic beta-cells isolated from obese hyperglycemic mice. Addition of 2 microM clonidine promptly inhibited glucose-stimulated insulin release, an effect accompanied by a lowering in both membrane potential and [Ca2+]i. Within minutes, the effect on Ca2+ was partly reversed, [Ca2+]i attaining a new level, although still significantly lower than in the absence of agonist. This late increase in [Ca2+]i was inhibited by 50 microM D-600, a blocker of voltage-activated Ca2+ channels. The inhibitory effects of clonidine on membrane potential, [Ca2+]i, and insulin release were abolished by 5 microM of the alpha 2-adrenergic antagonist yohimbine. Depolarization with high K+ increased [Ca2+]i also in the presence of clonidine, conditions accompanied by only a minute release of insulin. Secretion was, however, partly restored by subsequent addition of 20 mM glucose. Addition of 5 mM Ca2+ transiently reversed the effects of clonidine on both membrane potential and [Ca2+]i. Although the clonidine-induced repolarization should be enough for closing the voltage-activated Ca2+ channels with a resulting decrease in [Ca2+]i, a direct interaction of the agonist with these channels cannot be excluded. The fact that it was possible to increase [Ca2+]i with only a minor effect on insulin release suggests that the inhibitory effect of clonidine not only is due to a reduction in [Ca2+]i, but also involves interference with some more distal step in the insulin secretory machinery. PMID- 2892834 TI - Isolation of a sodium dodecyl sulfate-insoluble transglutaminase substrate from liver plasma membranes. AB - Rat liver plasma membranes contain transglutaminase activity and a large molecular weight protein complex which serves as a substrate for this enzyme. When plasma membranes were solubilized in sodium dodecyl sulfate and disulfide reducing agents the transglutaminase substrate was recovered in the detergent insoluble fraction. The insolubility of the complex suggested that it might be further studied by adsorbing membranes onto glass slides, then extracting with the detergent and reducing agent. After extraction, dark field light microscopy revealed numerous flattened sheets which varied in size from 4 to 12 micrometers. To confirm that these structures were the large molecular weight transglutaminase substrate, the plasma membranes were solubilized in sodium dodecyl sulfate and dithiothreitol and sedimented through a sucrose gradient containing the agent. The large molecular weight substrate was the only material found at the 1.11/1.23 g/cm3 interface. Microscopic examination showed the same structures previously observed on the glass slides. We conclude that the large molecular weight transglutaminase substrate is a sodium dodecyl sulfate-insoluble, morphologically distinct, protein complex. Due to its considerable size, nondissociable nature, and association with the lateral membrane, the sodium dodecyl sulfate-insoluble transglutaminase substrate may serve as a type of skeleton or scaffolding for this plasma membrane domain. PMID- 2892835 TI - Agonist-stimulated oscillations and cycling of intracellular free calcium in individual cultured muscle cells. AB - Receptor regulation of [Ca2+]i was monitored in individual BC3H-1 muscle cells with intracellularly trapped fura-2 using digital imaging analysis techniques. Activation of alpha 1-adrenergic or H1-histaminergic receptors resulted in multiple bursts, or oscillations, of elevated [Ca2+]i with an average interval frequency of approximately 1.8 min-1. The duration of oscillatory behavior was generally more prolonged in response to phenylephrine than in response to histamine. Additionally, a larger fraction of the cells responded with [Ca2+]i oscillations to phenylephrine (approximately 90%) than to histamine (approximately 60%), although the majority of cells produced oscillations in response to both agonists. In most cells, the receptor-mediated [Ca2+]i oscillations continued for several minutes in the absence of extracellular Ca2+, although the amplitude of the individual peaks gradually decreased. The activation of [Ca2+]i oscillations by H1-receptors was more dependent upon extracellular Ca2+ than those elicited by alpha 1-receptors, reflecting the greater dependency of the histaminergic response on Ca2+ influx. Readdition of Ca2+ to the incubation buffer resulted in the resumption of the [Ca2+]i oscillations. These results indicate that considerable cycling of Ca2+ between the cytoplasm and the endoplasmic reticulum must occur. Receptor-mediated [Ca2+]i oscillations were much more prevalent in subconfluent cells than in confluent cells, possibly due to increased coupling of the cells at higher densities. The cells were capable of responding independently of one another, since sister cells displayed unique temporal responses immediately following cell division. Thus, the linkage of receptor occupancy to [Ca2+]i elevation is a functionally unique property for each individual cell and can be influenced by epigenetic factors. PMID- 2892836 TI - Structure of the yeast HOM3 gene which encodes aspartokinase. AB - The yeast HOM3 gene has been cloned molecularly by complementation of a HOM3 mutant. The gene is located about 8 kilobase pairs from HIS1 and is present as a single copy in the yeast genome. Mutations in HOM3 result in a requirement for threonine and methionine (or homoserine) for growth and a lack of detectable aspartokinase activity. The nucleotide sequence of HOM3 predicts an enzyme 414 amino acids long that shows homology to the three Escherichia coli aspartokinases, indicating that it is the structural gene for yeast aspartokinase. An approximately 1800-base pair mRNA is transcribed from the HOM3 gene, initiating at several start sites, 80 and 70 base pairs downstream, respectively, from two TATA boxes. Upstream of the TATA boxes is a single TGACTC sequence. This sequence has been shown to be essential for regulation of several genes that encode amino acid biosynthetic enzymes by the general control system. However, no increase in aspartokinase mRNA is observed under general control derepressing conditions. PMID- 2892837 TI - Structural organization of the gene for rat liver-type arginase. AB - Liver-type arginase (EC 3.5.3.1) catalyzes the last step of urea synthesis and is expressed specifically in the liver of ureotelic animals. Expression of liver arginase is developmentally and hormonally regulated in coordination with other urea cycle enzymes. The gene for the rat enzyme was cloned and the structure determined. This gene is 12 kilobases long and is split into eight exons. All of the splice donor and acceptor sites conform to the GT/AG rule. The transcription initiation site was determined by nuclease S1 mapping and primer extension. A "TATA box"-like sequence and a "CAAT box"-like sequence are present 27 and 60 bases upstream from the cap site, respectively. Upstream and downstream from the cap site, there are several sets of direct repeats and inverted repeats and several sequences resembling the transcription factor Sp1 binding sites, the enhancer core sequences, the glucocorticoid receptor binding sites, the 12-O tetradecanoylphorbol-13-acetate responsive elements, and the putative elements for liver-specific expression of albumin genes. A 15-nucleotide sequence in the 5'-flanking region of the arginase gene is highly homologous with sequences in the 5'-flanking regions of the genes for rat ornithine carbamoyltransferase (EC 2.1.3.3) and for human argininosuccinate synthetase (EC 6.3.4.5), other two enzymes of the urea cycle. PMID- 2892838 TI - Bacterial synthesis of active rat stearyl-CoA desaturase lacking the 26-residue amino-terminal amino acid sequence. AB - Two clones containing inserts in pBR322 that together include the entire 1074 base open reading frame coding for the 358 amino acids of rat liver stearyl-CoA desaturase have been used to construct expression vectors for residues 3-358 and 27-358 fused to the first 6 residues of beta-galactosidase and several amino acids of the multiple cloning site of pUC8. Growth of transformed Escherichia coli under conditions for suppression of the lac promoter, followed by subsequent induction of these cultures results in the synthesis of higher levels of desaturase proteins than those found in induced rat liver. The proteins are almost completely associated with the membrane fraction of cell homogenates. Posttranslational iron insertion into the apoproteins, either in vitro with membrane preparations or by iron addition during induction, results in the formation of active holoenzyme which can be reconstituted with NADH cytochrome b5 reductase and cytochrome b5 to form an active stearyl-CoA desaturase system. The deletion of the first 26 amino-terminal amino acid residues does not affect either enzyme activity or membrane binding. Therefore, the unusual sequence of 11 residues containing 10 amino acids with hydroxyl groups plays no apparent significant role in either protein insertion into membranes or iron chelation. Since the protein product for residues 3-358 is processed even further to delete the initial 33 amino-terminal residues, the limiting polypeptide primary structure required for an active membrane-bound catalyst is even smaller than this initial deletion mutation indicates. PMID- 2892840 TI - Prolonged supersensitivity to noradrenaline of smooth muscle of the epididymal half of the rat vas deferens denervated by vasectomy. AB - 1 The effects of some sympathomimetic amines and of carbachol and potassium chloride upon the contractility of epididymal halves of the rat vas deferens have been examined in vitro at several times following vasectomy by medial transection of the vas deferens in vivo. The inhibitory effects of noradrenaline and the excitatory effects of potassium chloride upon prostatic halves of transected tissues were also studied. 2 Partially denervated epididymal segments, taken 2 days after surgery, were spontaneously active, and responses to KCl (80 mmol/l) and maximum responses to phenylephrine were enhanced. These effects were not observed with preparations taken at later times. Spontaneous activity and enhancement of responses to KCl were abolished by guanethidine (0.1 mumol/l). 3 Supersensitivity to noradrenaline was observed in fully denervated epididymal halves of vasa deferentia taken 7-183 days after transection. The supersensitivity consisted of a leftward shift in the log concentration-response curves for noradrenaline constructed upon operated, relative to those obtained upon unoperated preparations. Supersensitivity to phenylephrine but not to methoxamine or to carbachol was also evident. 4 The magnitude of the leftward shift in the log concentration-response curve for noradrenaline in operated epididymal segments approached that produced, in unoperated segments, by nisoxetine (0.1 mumol/l). This inhibitor of neuronal uptake did not enhance the potency of noradrenaline in operated segments. 5 Prazosin (50 nmol/l) antagonized the effect of phenylephrine upon both operated and unoperated epididymal segments. The antagonism was significantly greater upon operated segments than upon unoperated segments 4 and 28 days after surgery. 6 In prostatic segments, noradrenaline produced inhibition of field stimulation-induced twitches. Its potency was similar in both operated and unoperated preparations, and nisoxetine (0.1 mumol/l) potentiated its effects to a similar extent (approximately 70-fold) in control and operated tissues. Responses to KCl in this half of the vas deferens were essentially unaffected by vasectomy. 7 Taken together, these findings indicate that post-ganglionic denervation of the epididymal half of the rat vas deferens by medial transection (vasectomy) leads to a slowly developing and prolonged supersensitivity to noradrenaline which is primarily due to the loss of the neuronal uptake facility. Persistent adaptive changes in the effector cells are apparently minimal after this means of denervation. PMID- 2892839 TI - Interaction between amphetamine and alpha 2-postsynaptic adrenoreceptors in the rat submaxillary gland. AB - 1 The interaction between amphetamine and the alpha 2-adrenoreceptor agonists, clonidine and guanabenz, was studied in the submaxillary gland of anaesthetised rats. 2 Low doses of clonidine (10 micrograms/kg) and guanabenz (10 micrograms/kg) inhibited the secretory responses induced by methacholine and substance P, respectively. 3 Amphetamine (300 micrograms/kg) antagonized the inhibitory effects of both alpha 2-agonists. This dose of amphetamine alone did not show sialagogic effects. 4 Atropine (1 micrograms/kg) diminished the secretory responses to methacholine as much as clonidine (10 micrograms/kg). Amphetamine did not modify the blockade by atropine. 5 Guanabenz (10 micrograms/kg) markedly decreased the secretory responses to substance P, an effect that was also prevented by amphetamine. 6 Reserpine pretreatment (5 mg/kg, i.p., 18 h) did not alter the effect of amphetamine. 7 These results indicate that the interaction between amphetamine and alpha 2-adrenoreceptor agonists is unrelated to the indirect effect of this amine and suggest a direct interaction between the drug and postsynaptic inhibitory alpha 2-adrenoreceptors. PMID- 2892841 TI - Assessment of the effect of coronary artery bypass grafting on left ventricular performance by Doppler measurement of the aortic blood velocity during exercise. AB - The effect of coronary artery bypass grafting (CABG) on left ventricular (LV) function is studied noninvasively in 30 male patients with a mean age o 55.4 years using the continuous-wave Doppler technique of transcutaneous aortovelography (TAV). With a transducer applied in the suprasternal notch the main-stream aortic blood velocity recordings were obtained before and at maximum tolerated supine exercise both prior to, and six weeks after, CABG. From the TAV recordings the stroke distance (Sd: or the systolic velocity integral which is a measure of the stroke volume) and minute distance (Md: or the measure of cardiac output) were derived as well as the percentage changes in these parameters with exercise (% delta Sd and % delta Md successively). Whereas no significant change following CABG was observed in the resting values for Sd, a significant improvement in the maximal exercise values for Sd and Md as well as the % delta Sd and % delta Md was noticed after CABG (p less than 0.001). Prior to CABG the % delta Sd (an indicator of left ventricular function) was significantly lower in 13 patients with a history of an old myocardial infarction (MI). The % delta Sd in these 13 patients was also significantly lower than that in the 17 patients without a history of MI though the improvement in the % delta Sd following CABG was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892845 TI - Characterization of HMG CoA synthase activity of rat liver and CHO-K1 cells. AB - This report describes the characterization and partial purification of rat liver 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) synthase activity. A preliminary characterization of Chinese hamster ovary (CHO) cell HMG CoA synthase activity is also presented. Ion-exchange chromatography of ammonium sulfate precipitates of rat liver cytosol indicate the existence of two isoenzymes of HMG CoA synthase. These isoenzymes are physically, catalytically, and immunologically distinct. One of these isoenzymes, peak 1, resembles mitochondrial HMG-CoA synthase activity as evidenced by similarities in elution upon ion-exchange chromatography, inhibition by MgCl2, and cross reactivity with an antibody prepared against the mitochondrial enzyme. As peak 1 activity is unstable, further purification studies were performed on peak 2 activity. Peak 2 can be further resolved into two activities (peaks 2A and 2B) by gel filtration. In contrast, CHO-K1 cells (a permanent fibroblast line) possess only peak 2 type HMG CoA synthase activity. PMID- 2892842 TI - Clathrin-coated vesicle assembly polypeptides: physical properties and reconstitution studies with brain membranes. AB - The assembly polypeptides are an integral component of coated vesicles and may mediate the linkage of clathrin to the vesicle membrane. We have purified assembly polypeptides in milligram quantities from bovine brain by an improved procedure. Hydrodynamic and chemical crosslinking studies indicate that the protein is an asymmetric heterotetramer with a molecular weight of 252,000, containing two subunits of Mr 98,000-115,000, one subunit of 52,000, and one subunit of 16,000. Two-dimensional peptide maps of the subunits show that the 16- and 52-kD polypeptides are not derived from the higher molecular weight species, and that the group of bands at 98-115 kD are related. Electron microscopic visualization shows an essentially globular protein with one or two knob-like tails. We demonstrate a specific membrane protein binding site for 125I-labeled assembly polypeptides in 0.1 N sodium hydroxide-extracted bovine brain membranes based on the following criteria: (a) binding is displaceable by unlabeled ligand, (b) the binding site is destroyed by protease treatment of the membranes, and (c) the distribution of binding between vesicle-depleted membranes and coated vesicle membranes parallels the in vivo localization of assembly polypeptides and clathrin. This binding site is likely to be an integral membrane protein because (a) it is enriched in the sodium hydroxide-extracted membranes stripped of most of their peripheral membrane proteins, and (b) the binding site is partially extracted by 0.5% Triton X-100. A similar binding site appears to be present in coated vesicles. Clathrin binds to the hydroxide-stripped membranes in an assembly polypeptides dependent manner, and this binding is diminished by Triton extraction of the membranes. This assay may aid in identification of the membrane receptor for the assembly polypeptides. PMID- 2892843 TI - Estimation of the amount of internalized ricin that reaches the trans-Golgi network. AB - We have used a protocol for internalization of ricin, a ligand binding to plasma membrane glycoproteins and glycolipids with terminal galactosyl residues, and infection with the vesicular stomatitis virus ts 045 mutant in BHK-21 cells to determine whether internalized plasma membrane molecules tagged by ricin reach distinct compartments of the biosynthetic-exocytic pathway. At 39.5 degrees C newly synthesized G protein of ts 045 was largely prevented from leaving the endoplasmic reticulum. At the same temperature ricin was endocytosed and reached, in addition to endosomes and lysosomes, elements of the Golgi complex. When the temperature was lowered to 19.5 degrees C, no more ricin was delivered to the Golgi complex, but now G protein accumulated in the Golgi stacks and the trans Golgi network (TGN). Double-labeling immunogold cytochemistry on ultracryosections was used to detect G protein and ricin simultaneously. These data, combined with stereological and biochemical methods, showed that approximately 5% of the total amount of ricin within the cells, corresponding to 6-8 X 10(4) molecules per cell, colocalized with G protein in the Golgi complex after 60 min at 39.5 degrees C. Of this amount approximately 70-80% was present in the TGN. Since most of the ricin molecules remain bound to their binding sites at the low pH prevailing in compartments of the endocytic pathway, the results indicate that a fraction of the internalized plasma membrane molecules with terminal galactose are not recycled directly from endosomes or delivered to lysosomes, but are routed to the Golgi complex. Also, the results presented here, in combination with other recent studies on ricin internalization, suggest that translocation of the toxic ricin A-chain to the cytosol occurs in the TGN. PMID- 2892844 TI - A chloroquine-resistant Swiss 3T3 cell line with a defect in late endocytic acidification. AB - To investigate the role of acidification in cell proliferation, several cell lines resistant to chloroquine were isolated with the expectation that some would express altered endocytic acidification. The preliminary characterization of one of these lines, CHL60-64, is described. In contrast to endocytic mutants described previously, the initial phase of endocytic acidification, as measured by transferrin acidification, is normal in this cell line. However, a difference in subsequent endocytic acidification was observed in CHL60-64. In the parental cells, internalized dextran was fully acidified to approximately pH 5.5 within 1 h. In CHL60-64, the pH in the endocytic compartment was only 6.1 after 1 h and remained as high as 5.8 for at least 4 h. After an 8-h incubation, the pH decreased to 5.5, indicating that the second phase of acidification is only slowed in CHL60-64, and not blocked. Consistent with this retarded acidification, ATP-dependent acidification in vitro (as measured by acridine orange accumulation) was reduced in both the lysosomal fraction and the endosomal fraction isolated from CHL60-64. A decrease in the in vivo rate of acridine orange accumulation after perturbation with amine was also observed. In addition to amine resistance and defective acidification, CHL60-64 was found to be resistant to vacuolation in the presence of chloroquine and ammonium chloride, and was resistant to ouabain. Further studies on this new class of endocytosis mutant, in combination with existing mutants, should help to clarify the mechanisms responsible for the regulation of endocytic acidification. PMID- 2892846 TI - Protective effect of the glutamate antagonist, MK-801 in focal cerebral ischemia in the cat. AB - The effects of the glutamate N-methyl-D aspartate (NMDA) receptor antagonist, MK 801, upon ischemic brain damage has been examined in anesthetized cats. Focal cerebral ischemia was produced by permanent occlusion of one middle cerebral artery and the animal were killed 6 h later. The amount of early ischemic damage was assessed in coronal sections at 16 predetermined stereotactic planes. Pretreatment with MK-801 (5 mg/kg, i.v.), 30 min before occlusion of the middle cerebral artery significantly reduced the volume of ischemic damage (from 32.7 +/ 4.0% of the cerebral hemisphere in vehicle-treated cats to 16.2 +/- 4.5% in MK 801-treated cats). NMDA receptor antagonists that penetrate the blood-brain barrier, such as MK-801, merit further study as protective agents against ischemic brain damage. PMID- 2892847 TI - Micro-determination of clobazam and N-desmethylclobazam in plasma or serum by electron-capture gas chromatography. PMID- 2892848 TI - Correlation between reversed-phase high-performance liquid chromatography and plasma protein binding. AB - As hydrophobic interactions are involved in both reversed-phase liquid chromatography and plasma protein binding, the relationship between retention time and binding was investigated experimentally in two series of compounds. For betaxolol and its O-alkyl analogues, the nature of the O-alkyl group strongly influences the retention time on a Spherisorb CN 5-microns column. With 0.03 M acetate buffer (pH 5.6)-acetonitrile (60:40) as the mobile phase, k' values increase from 1.8 to 8.3 with a concomitant increase in plasma protein binding from 0.5% (R = H) to 88.2% (R = cyclopentylmethyl). The relationship between the free fraction and log k' is sigmoidal. In the second example, structural changes in the propyl side-chain of alpidem (a new anxiolytic) lead to minor variations in the protein binding: 98.9 to 84.9%. This slight decrease with the more polar metabolite is correlated with a sharp decrease in the k' values from 14.7 to 0.94 on a Supelcosil LC 18 DB column. Based on retention times, it should be feasible to predict qualitatively, if not quantitatively in some instances, plasma protein binding in a series of structurally similar compounds. PMID- 2892849 TI - Determination of 6-(2'-chlorophenyl)-4-hydroxy-4H-imidazo[1,5-a] [1,4]benzodiazepine-3-carboxamide, a mixed agonist-antagonist anxiolytic agent, in human plasma and urine by gas chromatography-negative-ion chemical-ionization mass spectrometry. AB - A simple, sensitive and specific assay was developed for the determination in plasma and urine of 6-(2'-chlorophenyl)-4-hydroxy-4H-imidazo[1,5-alpha] [1,4]benzodiazepine- 3-carboxamide, compound I, a mixed agonist-antagonist anxiolytic agent. A hexadeuterated analogue of the compound was added to plasma or urine as the reference standard. The titled compound was extracted with benzene at pH 11. Following evaporation of the solvent, the residue was reacted with pentafluoropropionic anhydride in the presence of triethylamine. The derivatizing reagents were evaporated, and the carbonitrile derivative of the analyte was extracted into ethyl acetate at pH 11. The residue remaining after removal of the ethyl acetate was silylated with bis(trimethylsilyl)trifluoroacetamide, and a portion of this solution was analyzed by gas chromatography-negative-ion chemical-ionization mass spectrometry. The mass spectrometer was set to monitor, in the gas chromatographic effluent, the M-. ion of the titled compound and its hexadeuterated reference standard. The ratio of these two ions was calculated and converted to a concentration of analyte using a calibration curve that was generated from the analyses of control plasma fortified with various amounts of analyte and a fixed amount of the hexadeuterated reference standard. The limit of quantitation of the assay was 1 ng/ml for plasma and urine. PMID- 2892850 TI - Assay of vecuronium in plasma using solid-phase extraction, high-performance liquid chromatography and post-column ion-pair extraction with fluorimetric detection. AB - An assay has been developed and validated for the routine monitoring of vecuronium in plasma. It consists of solid-phase extraction using C18 disposables as sample pre-treatment, high-performance liquid chromatography and post-column ion-pair extraction with fluorimetric detection. The fluorescent anion 9,10 dimethoxyanthracene-2-sulphonate (DAS) is used as the counter ion. The detection limit is ca. 5 ng/ml in plasma with a signal-to-noise ratio of 10. The assay is also applicable for monitoring vecuronium and its potential metabolites in other biological media, e.g., urine, bile and tissue (liver, kidney) homogenates. PMID- 2892851 TI - Biochemical indices of renal damage: separation of urinary alanine aminopeptidase by liquid chromatography. PMID- 2892852 TI - Simultaneous quantitative determination of tertatolol and its hydroxylated metabolite in human plasma and urine by gas chromatography-mass spectrometry. PMID- 2892853 TI - Functional opioid receptor sites in human placentas. AB - We characterized the presence of opioid peptide receptor sites in plasma membranes and cells from human midterm and term placentas. Incubations with [3H]ethylketo-cyclazocine (EKC) at increasing doses revealed the presence of high affinity, low capacity, opioid peptide receptor-specific binding of the kappa type. Scatchard analysis of the binding data showed, in the plasma membranes, linear plots at both stages of pregnancy with similar mean equilibrium association constants of 1.31 +/- 0.29 (+/- SE) X 10(9) mol/L-1 (n = 4) at midterm and 0.52 +/- 0.63 X 10(9) mol/L-1 at term (n = 4). In placental cells (n = 4) from term gestations, the binding plots were curvilinear; the first component had a Ka of 5.51 +/- 0.50 X 10(9) mol/L-1, and the second component had a Ka of 1.33 +/- 0.81 X 10(8) mol/L-1 (P less than 0.01). When standardized per mg tissue protein, the number of binding sites in plasma membranes increased from 13.8 +/- 9.8 fmol at midterm to 50.0 +/- 18.6 fmol at term (P less than 0.05). For term placental cells, the concentration of binding sites was 81.2 +/- 36.0 fmol for the high affinity sites and 713 +/- 390 fmol for the lower affinity sites. Specificity for the kappa-type of OPR was found based on the inability of mu- or delta-opioid peptides, as well as LHRH and TRH, to compete for [3H]EKC binding. Term placental cells incubated with various doses of opioid peptides had a 50% increase in placental lactogen production. The increase was significantly higher than controls only with kappa-agonists (P less than 0.05), maximal with 10(-9) mol/L EKC, and completely inhibited by 5 X 10(-6) mol/L naloxone. These results expand on previous data demonstrating the presence of opioid peptide receptor in placental plasma membranes and suggest a role for opioid peptides in regulating secretion of placental lactogen by placental cells. PMID- 2892854 TI - Effects of growth hormone (GH)-releasing hormone and somatostatin on GH secretion from individual human and monkey fetal anterior pituitary cells: modulation by thyroid hormones and glucocorticoids. AB - A reverse hemolytic plaque assay was used to measure the GH responses of fetal pituitary cells to GHRH, SRIH, T3 and glucocorticoids. Cells from eight human abortuses (18-22 weeks' gestation) showed accelerated plaque formation after treatment with 10(-7) mol/L GHRH-(1-44) [25.6 +/- 0.6% (+/- SE) of cells formed plaques (PFC); mean area, 14.5 +/- 2.7 X 10(4) micron2; all at 1 h], while 10(-7) mol/L SRIH-(1-28) slowed plaque formation (8.6 +/- 0.6% PFC; mean area, 4.2 +/- 0.8 X 10(4) micron2) vs. control (13.7 +/- 0.7% PFC; mean area, 5.3 +/- 0.8 X 10(4) micron2; all at 1 h). The proportion of PFC was equal in GHRH-treated and control groups by 4 h, suggesting that GHRH affects the amount of GH secreted per somatotroph rather than the number of cells that are preferentially responsive to GHRH. Qualitatively similar data were obtained using pituitary cells from four near-term rhesus fetuses. When cells were cultured in defined medium for 3 days, supplementation with T3 reduced basal GH secretion and attenuated the responses to GHRH. Culture with dexamethasone increased basal GH secretion and restored the responsiveness to GHRH. Dexamethasone also caused a shift in plaque area frequency distributions to patterns similar to those in serum-supplemented medium. We conclude that fetal somatotrophs are responsive to SRIH, GHRH, T3, and dexamethasone. Furthermore, glucocorticoids can maintain a subpopulation of fetal somatotrophs in the GHRH-responsive state. PMID- 2892856 TI - Antiserum to scrapie-associated fibril protein cross-reacts with Spiroplasma mirum fibril proteins. AB - Protease-resistant fibril proteins purified from Spiroplasma mirum and from Creutzfeldt-Jakob disease-infected brain tissues reacted with antisera to scrapie associated fibrils on Western immunoblot analysis. These data suggest that there are conformational similarities among spiroplasma proteins and infection-specific proteins of the transmissible spongiform encephalopathies. PMID- 2892857 TI - Semi-quantitative immunohistochemical studies on Thy-1 antigen expressed by thymic myoid cells. AB - Thy-1 antigen expression in the rat thymic myoid cell line R615B2 (Thy-1(+] and R613Ad (Thy-1(-] was studied with a semi-quantitative immunohistochemical assay without disrupting the cell cultures. With this assay, the quantity of Thy-1 antigen on R615B2 cells was detected separately in the cytoplasm and on the cell surface by the use of appropriate fixatives such as chilled ethanol and methanol + 0.3% H2O2. Extracellular Thy-1 antigen was also found in the culture supernatant of R615B2 cells. More than half of extracellular Thy-1 antigen remained in the supernatant even after 100,000 X g centrifugation. No form of Thy 1 antigen was detected at significant levels in R613Ad cells. PMID- 2892855 TI - Expression of type 1 fimbriae may be required for persistence of Escherichia coli in the catheterized urinary tract. AB - Long-term urinary catheterization results in polymicrobial bacteriuria and is complicated by fever, bacteremia, acute pyelonephritis, and death. Escherichia coli is a common urine isolate from catheterized patients and can persist for months. We hypothesized that fimbria-mediated adherence contributes to its persistence. For 1 year, urine specimens were collected from 51 patients greater than or equal to 65 years of age who were catheterized for greater than or equal to 30 days. E. coli was isolated at greater than or equal to 10(5) CFU/ml from 447 (36%) of 1,230 weekly urine specimens from 26 patients. Week 1 isolates from 52 definable episodes were tested for hemagglutination, hybridization with gene sequences from the pil and pap operons, in vitro adherence to catheter material, binding of 125I-labeled Tamm-Horsfall protein, hemolysin and colicin V production, and serum resistance. The proportions of isolates of short (1 week only), medium (2 to 11 weeks) and long (greater than or equal to 12 weeks) episodes of bacteriuria which expressed type 1 fimbriae as assayed by mannose sensitive hemagglutination were 59, 65, and 92%, respectively. Isolates with the pil operon (the genome for type 1 fimbriae) from episodes lasting greater than 1 week expressed mannose-sensitive hemagglutination more frequently (P = 0.011) than pil-positive isolates from episodes of less than or equal to 1 week. Isolates from episodes of greater than 1 week also bound significantly more Tamm Horsfall protein than isolates from episodes of less than or equal to 1 week (P = 0.044). Although nearly half of the isolates produced P fimbriae, an important virulence factor for the development of pyelonephritis, no correlation with persistence could be made. Overall, the E. coli isolates expressed traits similar to those of strains that caused cystitis. Type 1 fimbriae appear to be important for the persistence of E. coli in the long-term-catheterized urinary tract. PMID- 2892858 TI - Human T cell lines established from the cerebrospinal fluid of patients with human T lymphotropic virus type I-associated myelopathy (HAM). AB - T cell lines were established from the cerebrospinal fluid (CSF) lymphocytes of two patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM). These two interleukin-2 (IL-2)-dependent T cell lines have been cultured for more than 8 months without any accessory cells. The surface phenotype of these cells was CD2(+), CD4(+), CD8(-), Ia(+) and Tac(+). Southern blot hybridization analysis revealed the presence of HTLV-I provirus in these cells and C-type retrovirus particles were identified by electron microscopy. These findings indicate the presence of HTLV-I infected helper T lymphocytes in the CSF of the patients with HAM. These HTLV-I(+) T cell lines may be valuable for investigating the possible neutrotropism of HTLV-I and the role of HTLV-I in the pathogenesis of HAM. PMID- 2892859 TI - Biosynthesis of somatostatin in canine fundic D cells. AB - The observation that virtually all of the somatostatin-like immunoreactivity in the stomach consists of somatostatin-14 (S14), to the exclusion of somatostatin 28 (S28), suggests a unique pattern of prosomatostatin posttranslational processing. In order to examine the mechanisms by which S14 is produced from its precursor in the stomach, we investigated the biosynthesis of somatostatin in isolated canine fundic D cells. D cells pulse-labeled with [35S]cysteine revealed a cycloheximide inhibitable time-dependent incorporation of radioactivity into S14. A small fraction of radioactivity was incorporated into S28 but not into larger precursors. However, when the cells were incubated with monensin (1 microM), incorporation of radioactivity into a presumed somatostatin precursor was noted. Upon transfer of [35S]cysteine prelabeled cells to radioactivity-free medium, no conversion of S28 to S14 could be detected and the decrease of labeled S14 in cells correlated with a complimentary increase in the culture medium. Exogenous somatostatin inhibited somatostatin biosynthesis in a fashion that could be blocked by pertussis toxin pretreatment. Stimulation of prelabeled D cells with tetradecanoyl phorbol 13-acetate (10(-7) M) or forskolin (10(-4) M) for 2 h resulted in release of 41 and 33% of the newly synthesized radioactive S14, respectively, while only 9 and 6% of the total cell content of radioimmunoassayable somatostatin was secreted. These data suggest that: (a) somatostatin is synthesized in fundic D cells primarily as S14, (b) S14 is produced by rapid processing of a larger precursor but there is little, if any, conversion of S28 to S14, (c) somatostatin biosynthesis is autoregulated, and (d) newly synthesized S14 is preferentially released from D cells in response to stimulation. PMID- 2892861 TI - Relation of mesangial IgA glomerulonephritis to polymorphism of immunoglobulin heavy chain switch region. AB - We have investigated the switch regions of Ig heavy chain genes of patients with IgA glomerulonephritis (IgA-GN) using restriction fragment length polymorphism (RFLP) analysis. Genomic DNA from patients and controls was digested with the restriction endonuclease Sst I and transferred to nylon membranes using the Southern blot procedure and hybridized with a probe homologous to the switch region of the Ig C mu gene (S mu) which detects RFLPs in both S mu and the switch region of the Ig C alpha 1 gene (S alpha 1). A significant decrease in the frequency of the 2.6;2.1 kb heterozygous S mu phenotype was found in patients with IgA-GN (P = 0.003). With respect to the S alpha 1 region, there was a significant increase in the frequency of the 7.4 kb S alpha 1 phenotype (P = 0.002). In addition, a significant increase in the frequency of the 7.4 kb S alpha 1 allele was found (P = 0.0002). These results suggest that gene(s) within the Ig heavy chain loci may be important in the pathogenesis of IgA-GN. PMID- 2892863 TI - Efficacy without tolerance or rebound insomnia for midazolam and temazepam after use for one to three months. AB - Midazolam (15 mg) was compared with temazepam (30 mg) in a randomized, double blind, parallel group study. An initial screening period was followed by 3 days of placebo baseline, 4 to 12 weeks of nightly oral use of the medication and a 4 day placebo withdrawal period. One hundred seventy-five patients with chronic insomnia participated in this multicenter outpatient study. Because the elimination half-life of midazolam, a new trizolobenzodiazepine hypnotic, is short (1.3-2.2 hr) compared to temazepam's (12-16 hr), more problems with tolerance and rebound insomnia were expected to occur. Hypnotic efficacy (increased total sleep time, decreased wake time, and decreased sleep latency) was demonstrated for both medications over the entire 3-month period without the development of tolerance. In fact, if anything, efficacy increased with time on medication, suggesting possible facilitation or "inverse tolerance" effect. On withdrawal, sleep was improved compared with baseline, suggesting partial resolution of the insomniac condition rather than rebound insomnia. These effects were both statistically and clinically significant for midazolam, with 16% to 50% improvement in sleep measures. The results of this study suggest that patients with chronic insomnia may benefit from 30 to 90 days of treatment. A three-factor model that separates pharmacologic from behavioral and psychologic effects of hypnotics was proposed to explain these results in part. PMID- 2892862 TI - Effect of prazosin and beta-blocker monotherapy on serum lipids: a cross-over, placebo-controlled study. AB - The effects of prazosin and beta-blocker monotherapy on serum concentrations of triglycerides, cholesterol, and lipoprotein cholesterol were evaluated in 16 patients with mild to moderate essential hypertension in a single-blind, cross over, placebo-controlled study. Initially patients received a bid dose of either prazosin or a beta-blocker sufficient to maintain a sitting diastolic pressure below 95 mm Hg. After a placebo washout, patients were placed on the alternate medication. Fasting serum samples were obtained for lipid analysis during each treatment phase. Beta-blocker therapy was associated with undesirable changes in serum lipids as evidenced by increases in the concentration of total triglyceride (45%, P = .001), total cholesterol (4%, P = .05), LDL cholesterol (6%, P = .05) and VLDL cholesterol (21%, P = .05), and a decrease in the concentration of HDL cholesterol (-9%, P = .05). The ratios of total cholesterol to HDL cholesterol and LDL cholesterol to HDL cholesterol also increased by 15% (P = .005) and 18% (P = .005), respectively. No significant changes in any of the serum lipids were observed during prazosin administration. PMID- 2892860 TI - Human T cell leukemia virus-I-associated T-suppressor cell inhibition of erythropoiesis in a patient with pure red cell aplasia and chronic T gamma lymphoproliferative disease. AB - Human retroviruses have recently been linked with T cell lymphoproliferative disorders and with the acquired immune deficiency syndrome. We investigated the mechanisms for acquired pure red cell aplasia and cutaneous anergy in a patient with the chronic T gamma-lymphoproliferative disease (T gamma-LPD) syndrome. Patient marrow erythroid progenitors (BFU-E) were 17 +/- 9% of control and were selectively increased to 88-102% of control after marrow T cell depletion. Patient Leu 2+ suppressor T cells spontaneously produced high titers of human gamma-interferon and resulted in a concentration-dependent selective inhibition (74-91%) of BFU-E when co-cultured with autologous or allogeneic marrow. Conditioned media (CM) derived from patient Leu 2+ T cells similarly inhibited growth of autologous or allogeneic marrow BFU-E. The inhibitory factor derived from patient CM was acid-labile (pH 2) and sensitive to trypsin; prior treatment of patient T cells with anti-HLA-DR monoclonal antibody plus complement abrogated the suppressive effect of T cell-derived CM. Patient peripheral blood mononuclear cells (PBMC) were unable to support growth of cultured interleukin 2 (IL 2) dependent T cells, but responded to exogenous IL 2 in vitro with a 16-21-fold augmentation, relative to control, in mitogen-induced proliferation. Antibodies to HTLV-I core proteins p19 and p24 but not to HTLV-III proteins were detected in patient serum by Western blotting; patient cultured PBMC stained (7-11%) with antibodies to p19 and p24. Patient cultured PBMC demonstrated integrated HTLV-I genomic sequences by the Southern technique and expressed both specific HTLV-I genomic sequences by RNA dot blot plus reverse transcriptase activity. Utilizing a cloned DNA probe for the beta chain of the T cell receptor gene, patient PMBC demonstrated gene rearrangements providing presumptive evidence for clonality. The presence in serum of HTLV-I p19 and p24 antibodies, the expression of p19 and p24 core antigens on patient mononuclear cells, the evidence of HTLV-I proviral integration sequences and the expression of HTLV-I genomic sequences in patient cells, indicates infection with HTLV-I and raises the possibility of an etiologic link between human retrovirus infection and some instances of large granular lymphocytic leukemia (T gamma-LPD). PMID- 2892864 TI - Single bedtime dose of famotidine: assessment of its antisecretory action by 24 hour intragastric pH monitoring. AB - The antisecretory efficacy of a single bedtime dose of famotidine, a new potent H2-receptor antagonist, was evaluated by means of continuous 24-hour intragastric pH monitoring. Of 20 patients with duodenal ulcers, ten randomly received famotidine 40 mg at 10 PM and ten were monitored without medication for control. Famotidine regimen led to a remarkable reduction of gastric acidity in patients who were treated for duodenal ulcer and the drug-induced pH levels were significantly different (P less than .0001) from those of untreated controls. The antisecretory action lasted for 12 hours, which comprised the nocturnal period, whereas no important difference was found between the two groups for the most part of the daytime. The drug was able to keep intragastric pH above 4 units during almost 50% of the whole 24-hour period. These results confirm that famotidine is a powerful and long-acting H2 blocker that relieves gastric acidity during the night and morning hours when administered as a single bedtime dose of 40 mg. PMID- 2892865 TI - A comparison of the side effects of atenolol and propranolol in the treatment of patients with hypertension. AB - A single-blind study was conducted in 52 hypertensive patients, aged 25 to 68 years, to compare the side effects of an equally effective antihypertensive regimen of propranolol and atenolol. All patients had a history of side effects with beta-blocker therapy. Patients were treated with propranolol 40 to 160 mg bid for 8 weeks, followed by atenolol 50 to 100 mg given once daily for 8 weeks, and then rechallenged with the required dosage of propranolol for 8 weeks. Mean systolic and diastolic blood pressures were controlled during all three treatment phases. Side effects showed a definite trend toward improvement during the atenolol treatment phase. CNS side effects, in particular, showed significantly (P less than .05) reduced severity scores and overall incidence rates during the atenolol treatment phase. In conclusion, this study showed that at equally effective antihypertensive dosages the hydrophilic beta blocker atenolol produced significantly fewer CNS side effects than the lipophilic beta blocker propranolol. PMID- 2892866 TI - Labetalol in the treatment of hypertension in elderly and younger patients. AB - The efficacy and safety of labetalol therapy were evaluated in 20 patients 60 years and older with isolated systolic or diastolic hypertension and 19 patients aged younger than 60 years with diastolic hypertension. After a two-week placebo washout period, labetalol was titrated for up to four weeks (100-400 mg bid) until blood pressure control was achieved (standing systolic less than 160 mm Hg or greater than or equal to 10% reduction from baseline, and standing diastolic less than 90 mm Hg or a decrease of 10 mm Hg from baseline). Mean decreases in standing systolic and diastolic blood pressure from baseline were statistically significant for both age groups (greater than or equal to 60 years, -23/-13; less than 60 years, -18/-12, P less than .01). Control criteria were met in 18 (90%) older and 15 (79%) younger patients who then entered a four-week maintenance period. Sixteen (80%) of the older patients and six (32%) of the younger patients maintained blood pressure control on 200 mg or less of labetalol bid (P less than .05). Three patients, two of whom withdrew from the study, were judged to have experienced adverse events that were drug related. It was concluded that labetalol was effective and well-tolerated antihypertensive therapy in both elderly and younger patients. In addition, significantly less medication was required to achieve blood pressure control in the elderly. PMID- 2892867 TI - Overlap in the distribution of cholinergic and catecholaminergic neurons in the upper brainstem of the ferret. AB - The distribution of catecholaminergic and cholinergic neurons in the upper brainstem of the ferret were mapped by staining immunohistochemically two adjacent series of sections of brainstem for tyrosine hydroxylase and choline acetyltransferase, respectively. As in other species, large numbers of tyrosine hydroxylase-positive neurons are localized in the ventral tegmental area (A10), the substantia nigra (A9), and in A8. Tyrosine-hydroxylase-positive neurons in the dorsolateral pontine tegmentum (A4, A6, and A7--the locus coeruleus complex) of the ferret are rather diffusely distributed, as has been observed in other carnivore species such as the cat and the dog, but unlike the cat, these cells in the ferret display a relative uniformity in size and morphology. Choline acetyltransferase-positive neurons which extend in the ferret's pedunculopontine tegmental nucleus and ventral parabrachial area (Ch5) are relatively large cells that stain intensely for choline acetyltransferase, and their dendrites form prominent bundles in regions where unstained fibre tracts are prevalent. Choline acetyltransferase-positive neurons distributed in the laterodorsal tegmental nucleus (Ch6) are smaller than the cholinergic cells of Ch5, and they stain less intensely for choline acetyltransferase. Rostrally, there is little overlap between the catecholaminergic cell groups A8, A9, and A10 and the cholinergic cell groups of Ch5 and Ch6. Caudally, the Ch5 neurons extend some considerable extent into the locus coeruleus complex. In the region of overlap, no cells with staining for both tyrosine hydroxylase and choline acetyltransferase were observed, as was ascertained with a double staining method employing a combination of tyrosine hydroxylase immunofluorescence and choline acetyltransferase peroxidase-antiperoxidase immunohistochemistry. In conclusion, the ferret has a typically carnivore pattern for the distribution of catecholaminergic cells in the upper brainstem, and there is a significant overlap between the catecholaminergic and cholinergic cell groups in the dorsolateral pontine tegmentum. PMID- 2892868 TI - Cutaneous manifestations of Takayasu's arteritis. A clinicopathologic correlation. AB - Takayasu's arteritis is a chronic, granulomatous, large-vessel arteriopathy of unknown cause. We retrospectively reviewed the medical records of 38 patients with Takayasu's arteritis and identified 21 with cutaneous findings. Seven patients had lesions that were related to their systemic vasculitis. We found a Churg-Strauss granuloma, a pyodermatous leg ulcer, and inflammatory leg nodules in these patients. Biopsy specimens from three patients with presumed "erythema nodosum" did not support the clinical diagnosis but did show arteritis. In patients with Takayasu's arteritis, small-vessel inflammation, and other inflammatory lesions may be present, in addition to large-vessel disease. Histopathologic study is necessary to categorize the nature of inflammatory leg nodules of these patients. PMID- 2892869 TI - Emergency care in pediatric dentistry. AB - The emergency room records of 1,456 children who were treated at Children's Hospital of Pittsburgh with any oral complaint, during a single calendar year, were reviewed with the data entered into a computer. The data were tabulated and statistically analyzed. Trauma (676 visits) was responsible for 46 percent of the total visits, with boys representing a significantly higher percentage of trauma visits than girls (440 vs 236). The total number of trauma visits was also significantly higher for the youngest age-group (birth to three years). Soft tissue injuries represented a substantially higher percentage of trauma cases (58 percent), compared with dental injuries (35 percent) and bony injuries (3 percent). Emergency dental services are a viable part of emergency services in major population centers; emergency care is an essential component of overall dental services. PMID- 2892870 TI - Proposed delusional depression subtypes: preliminary evidence from a retrospective study of phenomenology and treatment course. AB - An analysis of the phenomenology and treatment course of 52 subjects with delusional depression suggests that there may be various subtypes: bipolar, early onset unipolar and possibly a late-onset unipolar. The bipolar subgroup tended to relapse in different but always psychotic directions, and was resistant to lithium carbonate treatment alone. Treatment refractoriness, delusional depressive recurrences, and a dementia-like presentation were associated with a small late-onset subgroup. A high rate of delusionally depressive relapses also characterized the early-onset unipolar group, however, patients with single episodes were found only in this subgroup. PMID- 2892871 TI - A comparison of morphologic and angiographic findings in long-term internal mammary artery and saphenous vein bypass grafts. AB - Internal mammary artery grafts are currently considered the conduits of choice for myocardial revascularization. Comparisons of long-term morphologic changes in internal mammary artery grafts and saphenous vein grafts and correlation with premortem angiography have not been reported. Eighteen internal mammary artery and 15 saphenous vein grafts that had been in place for 12 to 118 months (mean 56) in 18 patients were removed either surgically or at necropsy and examined histologically. Premortem angiograms were performed within 1 month of histologic study in 15 of these patients. Fibrointimal proliferation was more frequent in internal mammary artery than in saphenous vein grafts 8 [( 44%] of 18 versus 4 [27%] of 15; p = NS). In contrast, atherosclerosis was common in saphenous vein grafts but was extremely rare in internal mammary artery grafts (10 of 15 versus 1 of 18; p = 0.01). A good correlation was noted between the degree of narrowing estimated by angiographic and histologic measurements in both internal mammary artery grafts (d = 0.90) and saphenous vein grafts (d = 0.71). Accelerated atherosclerosis did not occur in internal mammary artery grafts, but was common in saphenous vein grafts. Fibrointimal proliferation was commonly associated with graft narrowing in internal mammary artery grafts and may be an important factor in late graft closure. This study also confirms that internal mammary artery grafts have greater longevity compared with saphenous vein grafts. PMID- 2892872 TI - Risk of anaphylaxis in patients receiving beta-blocker drugs. PMID- 2892873 TI - Human tonsillar IgE biosynthesis in vitro. II. Analysis of T cell regulation with monoclonal antibodies. AB - Phenotypes of T cells regulating human tonsillar IgE biosynthesis in vitro were studied by use of Leu 2a and Leu 3a monoclonal antibodies that recognize T cell subsets. B cells cultured with Leu 3a+-enriched populations (B cells plus T3a) produced significantly more IgE and IgG in the presence of pokeweed mitogen than B cells with the Leu 2a+-enriched populations (B cells plus T2a) (p less than 0.001 for IgE and p less than 0.001 for IgG). No significant differences were observed in IgE and IgG synthesis between the cultures of B cells alone and B cells plus T2a. T2a, but not T3a cells, significantly suppressed IgE synthesis (p less than 0.05 for geometric means and p less than 0.001 for percent suppression) when the cells were added to cultures of B cells plus T3a. Suppression of IgG synthesis was not observed under conditions that suppressed IgE synthesis, suggesting qualitative and quantitative differences in regulation of production of these isotypes. When T2a cells were irradiated, the suppressor activity disappeared. When graded numbers of T3a cells were added to B cells, it was noted that IgE synthesis first increased and then decreased as the numbers of T3a were increased. When the T3a cells were irradiated, IgE biosynthesis was suppressed at lower T/B ratios (less than 1 in four of five experiments) and was enhanced at higher T/B ratios (greater than 1 in all five experiments). Similar results were observed in experiments with OKT4 and OKT8 monoclonal antibodies. It is concluded that phenotypes of helper T cells for IgE synthesis are Leu 3a+ or OKT4+ and that IgE suppressors are predominantly Leu 2a+ or OKT8+ and are radiosensitive, as reported for regulation of other isotypes. However, it is suggested that Leu 3a+ and OKT4+ cells consist of radioresistant and radiosensitive helper cells and, presumably, a minor population of suppressor cells. PMID- 2892874 TI - [Comparison of the effects of carteolol and metipranolol eyedrops on the ventilatory and cardiovascular functions in asthmatics]. AB - Systemic effects of two topical B adrenergic blocking agents, carteolol and metipranolol, recently introduced in the treatment of open angle chronic glaucoma, were investigated in two groups of 10 asthmatic patients, according to a controlled trial device. Saline eye drops as placebo, then, 30 mn later beta blocker eye-drops, were instillated at usual dose. Heart rate, systolic and diastolic blood pressure, vital capacity (VC) and expiratory outflow (FEV1), were checked every 15 mn during 90 mn. They did not vary under placebo. After carteolol and metipranolol, heart rate decreased more than 10% in 7 out of 10 patients in each group (extreme individual changes: -16.7 and -25.0%). Bradycardia was always sino atrial. FEV1 was lowered in 3 patients with carteolol and in 6 with metipranolol (extreme individual values: -32.3 and -31.8%). If time is not taken in consideration, the lowest values were -8.6 +/-4.6% with carteolol and -17.9 +/- 3.3% with metipranolol. CV was reduced only in 1 patient under carteolol and 2 patients under metipranolol. Systemic blood pressure remained unchanged. 7 patients complained of ocular pain when metipranolol was instillated. Comparison of both ocular topics shows that metipranolol lowers heart rate and FEV1 more than carteolol, which has a sympathomimetic intrinsic activity. These two drugs have the same clinical efficiency. Our results point out the risks outcoming from their systemic diffusion, and the absolute necessity to comply with the general rules of good use of beta blockers, even with eye drops, mainly the contra-indications and the strict adjustment of individual doses. PMID- 2892876 TI - Clinical significance of elevated labeled TSH binding (LTB) activity in sera of patients with Graves' disease and other thyroid disorders. AB - Labeled TSH binding (LTB) of individual serum samples was monitored simultaneously using the thyrotropin binding inhibitor immunoglobulin (TBII) assay. In 643 TBII determinations, 86 sera (13.4%) showed elevated LTB. The incidence of elevated LTB in active Graves' patients (17.5%) was much higher than that of inactive Graves' patients (6.7%). After TBII activities were corrected by LTB, 79% of the active Graves' patients who had negative raw TBII were found to be positive. In patients with untreated active Graves' disease, the detectability of TBII increased from 85% to 91% after LTB correction, while those in inactive Graves' and other thyroid disorders did not increase so much (1.6 and 0%, respectively). Further, most of elevated LTB seen in other thyroid disorders were found to be different from those in Graves' disease by heat stability experiment. Serial observations of LTB and TBII in 24 Graves' patients showed 2 patterns. Parallel alterations were observed in 13 patients and reciprocal alterations in 11 patients. Patients showing parallel alteration had smaller goiter and were more sensitive to antithyroid drugs than those showing the latter pattern. PMID- 2892875 TI - Effects of thyroid stimulating immunoglobulin on function and morphology of xenotransplanted toxic diffuse, toxic nodular and normal thyroid tissue. AB - In order to examine the properties of human thyroid tissue, toxic diffuse goiter (TDG), toxic nodular goiter (TNG) and normal thyroid tissue were transplanted to nude mice. Starting 3 and 10 weeks after the transplantation the mice were given 14 daily injections of control serum or serum containing thyroid stimulating immunoglobulin (TSI). The uptake and release of 125I were repeatedly measured externally. The uptake and unstimulated release of 125I was lowest in TDG transplants, highest in TNG transplants, and intermediate in transplants of normal thyroid tissue. The findings were similar at both 3 and 10 weeks. Injections of TSI reduced the biological half-time of the tracer in TDG and normal transplants, but had no significant effect on TNG transplants. Light and electron microscopic studies showed that hyperplastic TDG tissue underwent involution after transplantation, whereas TNG and normal thyroid tissue remained unchanged. Injection of TSI reactivated TDG tissue; morphometry showed that the absolute and relative volumes of the follicle cells were more than doubled, with a corresponding decrease in the volume of the follicle lumen, and mitotic figures were common. Similar findings were seen in normal transplants, whereas the effect of TSI on TNG tissue was less pronounced. In summary, our observations show that serum from a patient with Graves' disease stimulated iodine release and induced follicle cell hyperplasia and probably also follicle cell multiplication in transplanted normal and TDG tissue, but had a lesser effect on TNG tissue. PMID- 2892877 TI - Thyroid stimulating immunoglobulin bioactivity during carbimazole therapy as measured by the cytochemical bioassay. AB - Most assays of thyroid stimulating immunoglobulin (TSI) are unsuitable for the quantitation of TSI during the treatment of Graves' hyperthyroidism because assay insensitivity results in some negative responses. Therefore the sensitive cytochemical bioassay was used to investigate the effect of carbimazole on TSI levels as a possible mechanism for the induction of the increased remission rate which is characteristic of thionamide therapy. Twelve patients were studied before therapy for de-novo Graves' hyperthyroidism; seven patients consented to a detailed prospectively study during block-replace therapy with carbimazole 10mg 6 hourly with a later addition of T3 20 micrograms 6 hourly when biochemically euthyroid. In addition thyroid hormone or T3 suppressed technetium (99m Tc) thyroidal uptake was monitored at between weekly and 3 monthly intervals, as well as the clinical findings, total T4 total T3, TSH, antimicrosomal antibody titers and immunoglobulins IgG, IgM and IgA. TSI was detected in all patients before treatment but there was no correlation with any other pretreatment measurements. During therapy TSI fell (in three different patterns) in 6 out of 7 patients studied for between 14-55 weeks (mean 29 weeks). TSI remained unchanged in one patient. Only the 99m Tc uptake correlated with TSI activity in the treated patients as a group (r = 0.71, p less than 0.001). TSI remained detectable in all patients, even in 4 patients in whom T3 suppression of 99m Tc was demonstrated. There is some evidence for a carbimazole effect lowering TSI activity, however relapse rate did not support this. T3 suppressed 99m Tc uptake may be a sensitive in vivo marker of TSI activity. PMID- 2892878 TI - Thyroid stimulating antibodies in rheumatoid arthritis: an in vitro phenomenon. AB - The purpose of the study was to evaluate the frequency of thyroid stimulating immunoglobulins and their possible effect in vivo in patients with rheumatoid arthritis. Thyroid stimulating antibodies (TSAb) were present in 17 (68%) of 25 patients with rheumatoid arthritis, whereas only 2 (8%) had thyrotropin binding inhibiting immunoglobulins (TBII). The groups with and without TSAb were comparable with regard to sex, age, anti-inflammatory drugs, serum thyroglobulin levels, antithyroglobulin and antimicrosomal antibodies, rheumatoid factor, as well as to the serum levels of thyroxine and 3, 5, 3'-triiodothyronine. A possible stimulating effect of TSAb in vivo was evaluated by an ultrasensitive immunoradiometric assay for TSH. Both groups had normal serum TSH levels, and no significant difference was found between the two groups suggesting that the demonstration of TSAb in vitro is not always associated with a stimulation of the thyroid gland in vivo. PMID- 2892880 TI - Erythema nodosum following a jellyfish sting. AB - At least 100 of the approximately 9,000 species of coelenterates are dangerous to humans. The most common syndrome following an envenomation is an immediate intense dermatitis, with characteristic skin discoloration, local pain, and systemic symptoms. In this case report, we describe a case of erythema nodosum with articular manifestations following envenomation with an unknown jellyfish. Serological testing of the victim revealed marked elevation of immunoglobulins G and M directed against Physalia physalis, the Portuguese man-of-war. The patient's condition did not respond to conventional topical therapy for coelenterate envenomation, but was successfully managed with systemic corticosteroid therapy. This case demonstrates that the emergency physician should consider a delayed reaction to a marine envenomation in any victim who presents with an acute dermatological disease following immersion in marine coastal waters. PMID- 2892879 TI - The effects of the antimuscarinic drugs pirenzepine and atropine on plasma portal levels of somatostatin and gastrin in the dog. AB - The effects of the antimuscarinic drugs pirenzepine and atropine on somatostatin and gastrin portal levels under basal conditions and during bethanechol infusion have been investigated in anesthetized dogs. Iv bolus administration of pirenzepine (1 mg/kg) or atropine (0.1 mg/kg), decreased gastrin concentrations, but did not affect basal somatostatin levels. During 120 min of bethanechol infusion (160 micrograms/kg/h) gastrin levels increased but somatostatin levels were unchanged. Pirenzepine (1 mg/kg iv bolus), administered at the 60th min of bethanechol infusion, decreased the gastrin concentrations, and markedly enhanced somatostatin levels. Under the same conditions atropine (0.1 mg/kg iv bolus) decreased gastrin levels, but had little or no effect on somatostatin levels. These results indicate that muscarinic receptors with similar affinity for pirenzepine and atropine mediate excitatory cholinergic influences on gastrin release. By contrast, muscarinic receptors with higher affinity for pirenzepine seem to be involved in the cholinergic inhibition of somatostatin release: by selectively blocking these receptors, pirenzepine may increase portal somatostatin levels. PMID- 2892882 TI - HAPPHY trial: primary prevention against coronary heart disease with beta blockers ruled out by HAPPHY? PMID- 2892881 TI - Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. AB - Men aged 40-64 years with mild to moderate hypertension [diastolic blood pressure (DBP) 100-130 mmHg] were randomized to treatment with a diuretic (n = 3272) or a beta-blocker (n = 3297), with additional drugs if necessary, to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease (CHD) events and death. Patients with previous CHD, stroke or other serious diseases, or with contraindications to diuretics or beta-blockers were excluded. If normotension (DBP less than 95 mmHg) was not achieved by monotherapy, other antihypertensive drugs were added, but the two basic drugs were not crossed over. Patients were assessed at 6-monthly intervals. The mean follow-up for end-points was 45.1 months. Blood pressure (BP) side effects and end-points were recorded in a standardized manner. Entry characteristics and the BP reduction achieved were very similar in both treatment groups. All analyses were made on an intention-to treat basis. The incidence of CHD did not differ between the two treatment groups. The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group. Total mortality and the total number of end-points were similar in both groups. The percentage of patients withdrawn due to side effects was similar, whereas the number of reported symptoms, according to a questionnaire, was higher for patients on beta-blockers. The incidence of diabetes did not differ between the two groups. Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers, and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD. Beta-blockers and thiazide diuretics were approximately equally well tolerated. The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group. Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications, including CHD, to a different extent. PMID- 2892883 TI - Sympatholytic effects of the intravenously injected alpha 1-adrenergic blocker, bunazosin, in anaesthetized rats. AB - Cardiovascular regulation during alpha 1-adrenergic blocker-induced vasodepression was investigated in urethane-anaesthetized rats. Intravenous (i.v.) injections of bunazosin, an alpha 1-blocker, elicited depressor responses which were accompanied by corresponding decreases in both heart rate and abdominal sympathetic discharge, dose-dependently. Those responses were not affected by the bilateral sino-aortic de-afferentation. Assuming that the site of action is in the central nervous system, bunazosin was injected intracerebroventricularly (i.c.v.). It produced hypotension accompanied by decreases in heart rate and abdominal sympathetic nerve activity. The magnitude of the responses was greater when bunazosin was injected i.c.v. than when injected i.v. Since these results indicated that the central alpha 1-adrenergic receptors mediate vasopressor responses, the effects of i.c.v. injections of an alpha 1-agonist, phenylephrine was explored. It elicited vasopressor responses accompanied by corresponding increases in heart rate and abdominal sympathetic nerve activity. Furthermore, i.c.v. pretreatment with bunazosin abolished the vasopressor responses to i.c.v. injections of phenylephrine. These results indicate that central alpha 1-adrenergic receptors mediate vasopressor responses and that i.v. injections of alpha 1-blockers affect the central alpha 1 receptors, to produce a decrease in sympathetic nerve activity. Consequently, alpha 1-adrenergic blockers decrease blood pressure not only by peripheral vasodilation but also by inhibition of the sympathetic outflow in rats. PMID- 2892884 TI - Polymorphism of the HLA-D region in American blacks. A DR3 haplotype generated by recombination. AB - The polymorphism of HLA class II molecules in man is particularly evident when comparisons between population groups are made. This study describes a DR3 haplotype commonly present in the American black population. Unlike the Northern European population in which almost all DR3 individuals are DQw2, approximately 50% of DR3-positive American blacks express a serologically undefined DQ allelic product. DNA restriction fragment analysis with the use of several unrelated individuals and an informative family has allowed us to identify unique DQ alpha- and beta-fragments associated with the DR3, DQw- haplotype. Based on fragment size, the DQ alpha genes of the DR3, DQw- and DRw8, DQw- haplotypes are similar as are the DQ beta genes of DR3, DQw-; DRw8, DQw-; and DR4, DQw- haplotypes. In addition, a DX beta gene polymorphism has been identified which is associated with some DR3 haplotypes including the American black DR3, DQw- haplotype. cDNA sequence analysis has revealed a DQw2-like alpha gene and a DQ beta gene which is similar to that previously described for a DR4, DQw- haplotype. It is postulated that recombination between DQ alpha and DQ beta genes and between the DQ and DX subregions has generated the various DR3 haplotypes and has played an important role in creating diversity in the HLA-D region. PMID- 2892885 TI - The E beta hot spot of recombination in wild-derived natural recombinant MHC haplotypes. Cross-over site mapping and the identification of a 1.0-kb E beta deletion in the p and w14 haplotypes. AB - Detailed molecular analysis of three wild-derived MHC haplotypes provided evidence for an important role of the E beta recombinational hot spot in the recent evolution of the mouse I region. Examination of RFLP and restriction maps of cloned DNA permitted the mapping of the natural cross-over events in the haplotypes carried by strains B10.GAA37 (w21) and B10.KPB128 (w19) to a fragment of DNA not exceeding 4.1 kb, which lies almost entirely within the intron separating the beta 1 and beta 2 exons of the E beta gene. In the w14 haplotype (strain B10.STC77), which appears to be a natural recombinant between a p-like parental haplotype and another wild-derived haplotype, the site of crossing over can be mapped to a segment between the beta 2 exon of the E beta gene (left border) and the E beta 2 gene (right border). This segment containing the cross over site in the w14 haplotype includes the E beta hot spot. In addition, the w14 haplotype as well as the standard p haplotype contain a deletion of approximately 1.0 kb in the second intron of the E beta gene, which may represent the product of an unequal cross-over event in a E beta recombinational hot spot. PMID- 2892886 TI - [The clinical value of sialyl SSEA-1 antigen in patients with gynecologic tumors]. AB - In order to estimate the clinical significance of sialyl SSEA-1 antigen, the antigen was measured with an "FH-6" Otsuka Kit in sera from patients with various gynecologic tumors. Among the patients with uterine malignancies and benign ovarian tumors, the incidence of elevated sialyl SSEA-1 antigen levels was very low. However, among the patients with ovarian malignancies, serum sialyl SSEA-1 antigen was significantly increased in the following order: clinical stage I (40%), stage II (67%) and stage III (75%). The serum antigen values were also correlated with the effect of treatment. In addition, high antigen values were also observed in all 14 malignant ovarian cyst fluids tested. The immunohistochemical localization of sialyl SSEA-1 antigen was determined by an immunoperoxidase method using FH-6 monoclonal antibody. A weak positive reaction was observed in normal glands of female genital tracts. However, the intense staining was shown on the mocus materials or on the luminal surface of some malignant glands as well as in the cytoplasm of some adenocarcinoma cells of gynecologic malignancies, although there were few positive cases or positive cells. Thus, sialyl SSEA-1 antigen appears to be a useful marker in the diagnosis of ovarian malignancies. PMID- 2892887 TI - [Medical vagotomy: a new effective antiemetic therapy in cisplatin-induced nausea and vomiting]. PMID- 2892889 TI - Improvement of tardive dyskinesia associated with electroconvulsive therapy. AB - This report describes a 54-year-old white woman who developed a persistent tardive dyskinesia after receiving neuroleptics for a manic episode. Although a variety of treatments were attempted, her tardive dyskinesia remained essentially unchanged for 5 years. It dramatically improved when she received electroconvulsive therapy for a depressive episode, however. This improvement has now been maintained for 14 months. Based on this observation, we suggest the use of electroconvulsive therapy in cases of persistent tardive dyskinesia that is unresponsive to treatment, if it is associated with a concurrent affective disorder requiring treatment. PMID- 2892888 TI - Strengthening of synaptic inputs after elimination of a single neurone innervating the same target. AB - The problem of 'competition' between neurones innervating the same target can be studied in simple neural systems such as the central nervous system of the leech and the lobster neuromuscular junction. Intracellular injection of pronase to kill selectively a single neurone shows that, in the leech, removal of one neurone is a sufficient signal to produce compensatory changes. After removal of a given neurone, only neurones of the same function respond to innervate the 'vacant territory'. This was shown both for a motor neurone (annulus erector) and sensory neurones (T or N). Thus the response is very specific. The lobster neuromuscular junction, with its multiple excitatory and inhibitory innervation, has advantages for the study of changes in synaptic efficacy of the remaining neurones after removal of a defined neurone releasing the same or a different transmitter. Killing the inhibitory neurone produced prolongation of the excitatory synaptic current because of a prolonged channel open time. When an excitatory axon is killed the remaining excitatory axon releases more transmitter. Over a period of 10 days, there is first a strengthening of existing synapses, then the appearance of new release sites and sprouting. Only those terminals of a neurone that innervate a territory with reduced innervation become stronger, while other terminals of the same axon remain normal. Cutting of axons produces different responses from those seen after killing single neurones. PMID- 2892890 TI - Kainic acid inhibits the synaptosomal plasma membrane glutamate carrier and allows glutamate leakage from the cytoplasm but does not affect glutamate exocytosis. AB - Kainate inhibits the exchange of D-aspartate into guinea-pig cerebrocortical synaptosomes. Kainate inhibits the Ca2+-independent efflux of endogenous glutamate in the presence of a trapping system for the released amino acid but potentiates a Ca2+-independent net efflux of endogenous and labelled glutamate and aspartate in the absence of the trap. Dihydrokainate has a similar effect. No discrepancy is seen between the release of endogenous and exogenously accumulated amino acid. These results are consistent with the presence of a slow leak of glutamate or aspartate from the cytoplasm independent of the kainate-sensitive Na+-cotransport pathway. In the presence of the trap, glutamate effluxes by both pathways, whereas in the absence of the trap, the Na+-cotransport pathway opposes the leak. Neither in the presence or absence of the glutamate trap does kainate induce, inhibit, or otherwise affect the Ca2+-dependent release of endogenous glutamate. The results enable many of the apparent complexities in the presynaptic actions of kainate to be resolved. PMID- 2892891 TI - Induction of glutamine synthetase in rat astrocytes by co-cultivation with embryonic chick neurons. AB - Co-cultivation of confluent rat astrocyte cultures with embryonic chick neurons resulted in induction of glutamine synthetase activity in the astrocytes. This induction of glutamine synthetase in astrocytes by neurons was independent of induction by hydrocortisone and forskolin, but was dependent on the length of co cultivation and the number of neurons present in the co-culture. Cycloheximide and actinomycin D inhibited the induction of glutamine synthetase in astrocytes by neurons, whereas cytosine arabinoside had no apparent effect. Results suggest that this induction of glutamine synthetase in astrocytes is mediated by cell contact with neurons and may represent a specific neuronal and glial interaction. PMID- 2892892 TI - Interaction of L-prolyl-L-leucyl glycinamide with dopamine D2 receptor: evidence for modulation of agonist affinity states in bovine striatal membranes. AB - The role of the hypothalamic tripeptide L-prolyl-L-leucyl-glycinamide (PLG) in modulating the agonist binding to bovine striatal dopamine D2 receptor was investigated using a selective high-affinity agonist, n-propylnorapomorphine (NPA). PLG caused an enhancement in [3H]NPA binding in striatal membranes in a dose-dependent manner, the maximum effect being observed at 10(-7)-10(-6) M concentration of the tripeptide. The Scatchard analysis of [3H]NPA binding to membranes preincubated with 10(-6) M PLG revealed a significant increase in the affinity of the agonist binding sites. In contrast, there was no effect of PLG on the binding pattern of the antagonist [3H]spiroperidol. The antagonist versus agonist competition curves analyzed for agonist high- and low-affinity states of the receptor displayed an increase in the population and affinity of the high affinity form of the receptor with PLG treatment. The low-affinity sites concomitantly decreased with relatively small change in the affinity for the agonists. Almost similar results were obtained when either NPA or apomorphine was used in the competition experiments. A partial antagonistic effect of PLG on 5' guanylylimidodiphosphate [Gpp(NH)p]-induced inhibition of high-affinity agonist binding was also observed, as the ratio of high- to low-affinity forms of the receptor was significantly higher in the PLG-treated membranes compared to the controls. Direct [3H]NPA binding experiments demonstrated that PLG attenuated the Gpp(NH)p-induced inhibition of agonist binding by increasing the EC50 of the nucleotide (concentration that inhibits 50% of the specific binding). No effect of PLG on high-affinity [3H]NPA binding, however, could be observed when the striatal membranes were preincubated with Gpp(NH)p.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892893 TI - Analysis of the 5' region of the human tyrosine hydroxylase gene: combinatorial patterns of exon splicing generate multiple regulated tyrosine hydroxylase isoforms. AB - A single human gene has been described to encode multiple tyrosine hydroxylase (TH) mRNAs. The study of this variation has been extended by S1 mapping experiments and by analysis of the 5' region of the TH gene. Four different mRNAs were found to originate solely from alternative splicing of two exons. Comparison of the 5' flanking regions of human and rat genes discloses several highly conserved segments, likely to play an important role in the regulation of TH gene expression. PMID- 2892894 TI - Antiserum to scrapie-associated fibril protein reacts with amyloid plaques in familial transmissible dementia. AB - Scrapie-associated fibrils (SAF) are disease-specific markers for the unconventional agent-induced, transmissible spongiform encephalopathies. Polyclonal rabbit antiserum to SAF protein was reacted with brain sections from scrapie-infected mice, two familial cases of transmissible dementia, and three cases of Alzheimer's disease (AD). Specific immunostaining of cerebral amyloid plaques occurred in the scrapie-infected mice and in the two familial cases of transmissible dementia. No immunoreactivity was detected in senile plaques or neurofibrillary tangles in the three cases of AD. Our results suggest that SAF, the causative pathogenic agent, and extracellular deposits of amyloid in the brain are closely related. Immunohistochemical detection of SAF protein could serve as a useful diagnostic adjunct in the postmortem evaluation of difficult cases of dementia. The identification of SAF protein in the brains of two affected members of a family combining the clinical and pathological features of Creutzfeldt-Jakob disease (CJD) and the Gerstmann-Straussler syndrome (GSS) substantiates earlier conclusions of a nosological relationship between the two. Our study provides further evidence of the similarity of SAF protein to prion protein (PrP 27-30). PMID- 2892895 TI - Comparative studies on the effects of beta-adrenergic blockers in essential tremor. AB - To establish the criteria for the selection of a beta-adrenergic blocking agent (beta-blockers) suitable for the long-term treatment of tremor, 20 patients with essential tremor were treated with five different types of beta-blockers. All beta-blockers were effective for essential tremor, but their efficacy differed. The weaker the intrinsic sympathomimetic activity (ISA) and the more marked the membrane stabilizing activity (MSA), the more marked was the anti-tremor effect. Propranolol, which showed the strongest anti-tremor effect, had no ISA, but its long-term administration induced symptoms of heart failure, such as pretibial oedema, in most cases. In most of these cases, when propranolol was replaced by indenolol, which showed a very slight ISA, the pretibial oedema subsided and well controlled tremor was maintained over a long period. With regard to efficacy and usefulness, it was thought that the beta-blockers with a very slight ISA and a marked MSA, such as indenolol, was most suitable for the long-term treatment of essential tremor. PMID- 2892896 TI - Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists. AB - The antagonist pharmacology of glutamate neurotoxicity was quantitatively examined in murine cortical cell cultures. Addition of 1-3 mM DL-2-amino-5 phosphonovalerate (APV), or its active isomer D-APV, acutely to the exposure solution selectively blocked the neuroexcitation and neuronal cell selectively blocked the neuroexcitation and neuronal cell loss produced by N-methyl-D aspartate (NMDA), with relatively little effect on that produced by either kainate or quisqualate. As expected, this selective NMDA receptor blockade only partially reduced the neuroexcitation or acute neuronal swelling produced by the broad-spectrum agonist glutamate; surprisingly, however, this blockade was sufficient to reduce glutamate-induced neuronal cell loss markedly. Lower concentrations of APV or D-APV had much less protective effect, suggesting that the blockade of a large number of NMDA receptors was required to acutely antagonize glutamate neurotoxicity. This requirement may be caused by the amplification of small amounts of acute glutamate-induced injury by subsequent release of endogenous NMDA agonists from injured neurons, as the "late" addition of 10-1000 microM APV or D-APV (after termination of glutamate exposure) also reduced resultant neuronal damage. If APV or D-APV were present both during and after glutamate exposure, a summation dose-protection relationship was obtained, showing substantial protective efficacy at low micromolar antagonist concentrations. Screening of several other excitatory amino acid antagonists confirmed that the ability to antagonize glutamate neurotoxicity might correlate with ability to block NMDA-induced neuroexcitation: The reported NMDA antagonists ketamine and DL-2-amino-7-phosphono-heptanoate, as well as the broad-spectrum antagonist kynurenate, were all found to attenuate glutamate neurotoxicity substantially; whereas gamma-D-glutamylaminomethyl sulfonate and L-glutamate diethyl ester, compounds reported to block predominantly quisqualate or kainate receptors, did not affect glutamate neurotoxicity. The present study suggests that glutamate neurotoxicity may be predominantly mediated by the activation of the NMDA subclass of glutamate receptors--occurring both directly, during exposure to exogenous compound, and indirectly, due to the subsequent release of endogenous NMDA agonists. Given other studies linking NMDA receptors to channels with unusually high calcium permeability, this suggestion is consistent with previous data showing that glutamate neurotoxicity depends heavily on extracellular calcium. PMID- 2892897 TI - Identification of the neuropeptide transmitter proctolin in Drosophila larvae: characterization of muscle fiber-specific neuromuscular endings. AB - The cellular localization of the peptide neurotransmitter proctolin was determined for larvae of the fruitfly Drosophila melanogaster. Proctolin was recovered from the CNS, hindgut, and segmental bodywall using reverse-phase HPLC, and characterized by bioassay, immunoassay, and enzymatic analysis. A small, stereotyped population of proctolin-immunoreactive neurons was found in the larval CNS. Several of the identified neurons may be efferents. In the periphery, proctolin-immunoreactive neuromuscular endings were identified on both visceral and skeletal muscle fibers. On the hindgut, the neuropeptide is associated with endings on intrinsic circular muscle fibers. We propose that the hindgut muscle fibers are innervated by central neurons homologous to previously described proctolinergic efferents of grasshoppers. The segmental bodywall innervation consists of a pattern of segment-specific junctions on several singly identifiable muscle fibers. While it is generally accepted that Drosophila muscle fibers are innervated by glutamatergic motoneurons, our data indicate that a specialized subset of muscle fibers are also innervated by peptidergic efferents. PMID- 2892898 TI - Dentate granule cells are essential for kainic acid-induced wet dog shakes but not for seizures. AB - The purpose of this study was to determine the role that dentate granule cells play in wet dog shakes (WDS), behavioral seizures, and hippocampal cell loss caused by systemic administration of kainic acid (KA). Rats were given bilateral injections of colchicine (COL) into the hippocampal formation to selectively lesion dentate granule cells. Two weeks later, they were injected subcutaneously with KA and were observed for WDS and seizures. Seizures were terminated with pentobarbital 2.5 hr after KA injection, and the rats were killed 48 hr later. The integrity of hippocampal cell populations and projections to the hippocampal formation from entorhinal cortex was assessed with radioimmunoassay and immunostaining for methionine-enkephalin (ME) and dynorphin (DYN) A, as well as with Timm and Nissl staining. Results indicate that COL injections eliminated KA induced WDS, did not affect the latency to onset of seizures, and potentiated KA induced cell loss in the CA3 region of hippocampus. COL lesions eliminated ME and DYN immunostaining of granule cells, but not ME immunostaining of entorhinal afferents to the dentate gyrus or Ammon's horn. These findings indicate that granule cells are an essential neuronal link in the expression of KA-induced WDS, but that seizures propagate along other pathways in the limbic system. PMID- 2892899 TI - Effect of partial denervation and terminal field expansion on neuromuscular transmitter release and nerve terminal structure. AB - The efficacy of evoked ACh release by intact and newly sprouted terminals in response to partial denervation and expansion of the motor neuron terminal field was studied in mouse soleus muscle after section of the L-5 spinal root. From 2 to 4 d after partial denervation until 90 d later, only 3-7 motor units of the normal 21 remained. Regeneration of the dissected nerve was prevented while the remaining motor units were sprouting. The indirect twitch, which was only 20% of direct twitch tension 2-4 d after nerve section, recovered between 28 and 50 d postoperatively. However, the depression of twitch in low Ca/high Mg solution, which was equal to control 2-3 d postoperatively, was 2-3 times more depressed than control by 50 d and remained so up to 90 d. This indicated persistent reduction of the safety factor in sprouted motor units. Intracellular measurement of quantal content in 0.4 mM Ca, 2.75 mM Mg revealed 2 groups of nerve terminals in partially denervated muscle. The quantal content of the first group was greater than contralateral control at earlier times (28-50 d) and only slightly greater than control later (74 and 90 d). This group consisted of the original undenervated terminals, since it was associated with normal miniature endplate potential (MEPP) frequency and end-plate potential (EPP) latency, and presumably with the class of fibers with normal (zinc iodide osmium-stained) nerve terminal morphology and occasional large myelinated preterminal axons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892900 TI - Glycine and glycine receptor immunoreactivity in brain and spinal cord. AB - To study the distribution of glycine immunoreactive neurons in the spinal cord and brain, antisera were raised against glycine conjugated to protein carriers. High-titer rabbit glycine antiserum was purified by affinity chromatography. Testing against other amino acids and peptides with immuno dot blots and ELISA assays showed little apparent cross-reaction with glutamate, aspartate, glutamine, taurine, and 17 other amino acids and related compounds. Similarly, the antiserum showed little apparent recognition of glycine when glycine was incorporated into peptides. A slight cross-reactivity with GABA, beta-alanine, and cysteine was found. Immunocytochemical labeling of tissue sections could be blocked with glycine conjugated to a heterologous carrier protein but not by other amino acids conjugated to that protein. Immunocytochemistry at the light microscope level with immunofluorescence and silver-intensified colloidal gold revealed a wide distribution of glycine-like immunoreactivity throughout all laminae of the rat spinal cord and in all segments studied from the cervical, thoracic, lumbar, and sacral cord. Immunoreactive boutons were found terminating on both cell bodies and on dendrites. Ultrastructural analysis with postembedding colloidal gold immunocytochemistry demonstrated large numbers of immunoreactive boutons making symmetrical type synapses with neuronal perikarya, including motor neurons, and with proximal and distal dendrites. Presynaptic glycine immunoreactive boutons were found in both ventral and dorsal horn. Immunoreactivity was concentrated over regions rich in vesicles, and over mitochondria in immunoreactive boutons, but not over mitochondria in postsynaptic dendrites. Glycine-immunoreactive perikarya were identified both in the dorsal horn and in the ventral horn. Myelinated and unmyelinated glycine-immunoreactive axons were noted both in the gray and white matter of the cord. The density of immunoreactive axons varied in the white matter, with the greatest number of immunoreactive axons found in the white matter adjacent to the gray matter in lateral and ventral white. Significantly fewer immunoreactive axons were found in the white matter of the dorsal columns. Myelin sheaths around axons were unlabeled. The distribution of glycine-immunoreactive boutons correlated well with the distribution of glycine receptor immunoreactivity on postsynaptic elements of the spinal cord, tested with different monoclonal antisera against strychnine-purified glycine receptor. Glycine receptor immunoreactivity was found throughout the gray matter of both rat and primate.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2892901 TI - Health problems of data entry clerks and related job stressors. AB - A study was made of health problems reported by data entry clerks working in two large data pools within the Quebec Public Service Administration. In order to collect the data, 350 clerks answered a questionnaire, representing a return rate of 92%. The results indicate that, in comparison with women in other occupations, the data entry clerks have a high rate of occurrence of psychiatric symptoms (measured by the Ilfeld index) as well as a high degree of use of over-the counter and prescription drugs. In addition, these two problems are more prevalent in full-time clerks than in part-time clerks. The psychiatric symptoms appear related to the combined influence of two main factors: work overload and the monotony of work specialization. A third factor, the quality of the relationships among workers in the pool, also seemed to affect the regular full time clerks. PMID- 2892902 TI - Hypokalemia and respiratory arrest in an infant with status asthmaticus. PMID- 2892903 TI - Gastrointestinal peptide profile in children with celiac disease. AB - In order to investigate if a plasma profile of gastrointestinal peptides reflects changes in jejunal mucosa in celiac disease, we studied basal and postprandial plasma levels of gastrin, secretin, somatostatin, vasoactive intestinal polypeptide (VIP), and neurotensin in children with untreated and treated celiac disease and in a control group of children. Basal and 30-min postprandial secretin concentrations were statistically significantly lower in untreated celiac children compared to both treated celiac (p less than 0.01 and p less than 0.05, respectively) and control children (p less than 0.001). Plasma secretin levels 30 min after a breakfast meal were also statistically significantly lower (p less than 0.001) in treated celiac children with respect to the control group. In both untreated and treated celiac groups, basal and postprandial plasma levels of somatostatin and VIP were statistically significantly decreased (p less than 0.001) compared to control children. Moreover, there was a significant rise in postprandial levels of neurotensin after a breakfast meal in untreated celiac children. On the contrary, there was no rise of neurotensin in healthy children. These findings seem to indicate that determination of plasma profile of gastrointestinal peptides in children with celiac disease may be useful in monitoring the development of this disease and, thus, the number of jejunal biopsies could be decreased. PMID- 2892904 TI - Use of a long-acting somatostatin analogue (SMS 201-995) in controlling a significant ileal output in a 5-year-old child. AB - We report the efficacy of a long-acting somatostatin analogue, associated with conventional therapy, in controlling profuse ileostomy losses in a child with short bowel syndrome following a volvulus. The first therapeutic effects of the treatment [50 to 100 micrograms/day of SMS 201-995 (Sandoz Ltd.) subcutaneously] appeared 48 h after institution. Ileal output was reduced on an average from 1,800 to 600 ml. The transit time to the ileostomy was prolonged from 20 to 360 min. The loss of chloride and sodium was reduced. Clinical tolerance was good. This treatment allowed rapid weaning of parenteral nutrition and implementation of a constant rate enteral infusion with rapid nutritional restitution. Hospitalization was shortened and this treatment raises future opportunities in the short bowel syndrome. PMID- 2892905 TI - Differential distribution of digestive enzymes in isolated epithelial cells from developing human fetal small intestine and colon. AB - The human fetal colon has morphological and biochemical characteristics similar to that of the small intestine during development. A comparative study of these two organs was undertaken by selectively isolating their respective epithelium at different ages of gestation. Histological and biochemical analysis revealed a complete and selective removal of the epithelium from the underlying tissue regardless of their stage of development. Intestinal and colonic epithelial cells showed substantial differences with respect to protein content and distribution. All brush border membrane enzymes studied were present in the colon, although in much lower quantities than in the corresponding intestine. Between 90 and 99% of total disaccharidases, glucoamylase and gamma-glutamyl transpeptidase activities were recovered in the isolated cells. Epithelial content and distribution of alkaline phosphatase (ALP) activity differed markedly, however, between these two tissues. More than 45% of intestinal ALP activity was of nonepithelial origin at 15 weeks, and this percentage increased in a craniocaudal fashion to reach greater than 93% in the 18-week-old colon. Inhibition studies using phenylalanine and levamisole showed that these intestinal and colonic isoenzymes are similar in nature although they differ in their respective distribution. The use of pure fractions of epithelial cells provides an ideal system in which to compare specifically the functional development of intestinal and colonic epithelium. PMID- 2892906 TI - [Reactions and interactions of drugs according to "Drug Reactions and Interactions" by P.F. D'Arcy]. PMID- 2892907 TI - Investigations of the solubilization kinetics of binary mixtures of non-polar oils by non-ionic surfactants. AB - An investigation of the solubilization kinetics of binary mixtures of non-polar oils by a non-ionic surfactant has been made using the drop-on-fibre technique. Variables studied were the oil composition, surfactant concentration and the temperature. Rates vary linearly with the surfactant concentration for all oil compositions. The observed rate during nearly total solubilization of each oil drop was constant, implying that in these systems solubilization is non selective. The rates increase as the lower consolute (cloud) temperature of the surfactant is approached. Activation energies of the solubilization process are shown to be independent of the oil composition for the system studied. This suggests that the important stage of the process involves dissociation of the surfactant micelles. PMID- 2892908 TI - Characterization of in-vitro drug release and biological activity of methotrexate bovine serum albumin conjugates. AB - Two series of methotrexate (MTX)-bovine serum albumin (BSA) conjugates have been prepared containing either 96 +/- 16 mg (mean +/- s.d.) or 32 +/- 13 mg of MTX per gram of conjugate. The conjugates released MTX in-vitro in a biphasic manner, the release rate being dependent on the quantity of MTX in the conjugate and on the pH of the release medium. An initial rapid release over 6 h appears to be due to physically adsorbed MTX with the slower secondary release due to covalently bound drug. The conjugates retain a degree of antineoplastic activity in-vitro, but this might be related to the small fraction of MTX that is tightly physically bound. PMID- 2892910 TI - In-vitro biotransformation of antipyrine, lignocaine and propranolol in the liver of rats with turpentine-induced inflammation. AB - In rats with inflammation induced by turpentine injection, changes in drug disposition occur in-vivo and in the perfused isolated liver. Therefore the biotransformation of a low extraction drug, antipyrine, and of two high extraction drugs, lignocaine and propranolol, has been evaluated in the 9000g supernatant fraction of the liver of turpentine-treated rats. Aminopyrine N demethylase activity and cytochrome P450 content were also measured. Turpentine treatment significantly reduced the in-vitro breakdown of the three drugs; aminopyrine N-demethylase activity and cytochrome P450 content were also decreased. Similar results were found in the proadifen-treated rats, except that in those, the cytochrome P450 content was slightly increased. The changes in drug disposition seen after turpentine-induced inflammation, could therefore be due in part to a change in hepatic enzymatic activity. PMID- 2892909 TI - The activity of 25 paroxetine/femoxetine structure variants in various reactions, assumed to be important for the effect of antidepressants. AB - Structure-activity relationships for 25 structural variants around the 5 hydroxytryptamine (5-HT) uptake inhibitors paroxetine and femoxetine have been investigated. Three parameters related to the 5-HT system were investigated: (i) The inhibition of [3H]5-HT uptake into rat brain synaptosomes, (ii) the inhibition of [3H]paroxetine binding to rat neuronal membranes and (iii) the effect of the compounds on the affinity of [3H]imipramine for the human platelet membrane binding site, measured as the dissociation rate of the [3H]imipramine human platelet membrane binding site complex. A highly significant correlation was found for 5-HT uptake inhibition and inhibition of [3H]paroxetine binding for the different substances, indicating that the two parameters are closely connected. However the slope of the regression line was only 0.6 and not 1.0; this may indicate that [3H]paroxetine binding is necessary, but not sufficient for 5-HT uptake inhibition. No correlation was found between the inhibition of [3H]paroxetine binding and the affinity of the compounds for the [3H]imipramine binding site complex. The two binding sites are therefore probably situated on different parts of the 5-HT transport system, the [3H]paroxetine binding site being part of the 5-HT transport mechanism whereas the [3H]imipramine binding site may represent a site modulating the activity of, and affinity for, 5-HT in the 5-HT transport mechanism. Structure-activity relationships among the substances showed that stereochemical changes from (-)- to (+)-trans changed the activity towards both 5-HT uptake inhibition and [3H]paroxetine displacement for most of the (-)-/(+)-pairs. The substitution of -H with -F or -CH3 also affected the activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892911 TI - Effect of triglyceride on small intestinal absorption of cefoxitin in rats. AB - Coadministration of trilaurin or monolaurin with sodium cefoxitin increased its absorption from the small intestine of the rat. Its absorption from the rectum was effected to a lesser extent except when lipase was present. Lipase, a natural constituent of the small intestine fluid, may therefore be essential for the adjuvant action of trilaurin on cefoxitin absorption across the intestinal membrane. Among the triglycerides used, trilaurin and tricaprin were the most effective enhancers of cefoxitin absorption. Both the rate of degradation of triglyceride to its fatty acid component and subsequently the rate of fatty acid absorption were factors influencing the enhancing action. Maintenance of fatty acid concentration at the small intestinal absorption site was shown to be necessary to obtain a cefoxitin bioavailability of up to 70%. PMID- 2892913 TI - The neuromuscular blocking effect of trimetaphan alone and in combination with different non-depolarizing muscle relaxants in the rat. AB - The effect of trimetaphan alone and in combination with pancuronium, tubocurarine or metocurine (dimethyl tubocurarine) has been examined on the rat phrenic nerve diaphragm preparation. Trimetaphan alone produced neuromuscular blockade in an all-or-none fashion once a concentration of between 2.39 X 10(-4) and 3.00 X 10( 4) M had been exceeded. Concentrations of trimetaphan below this threshold produced a dose-dependent potentiation of all three non-depolarizing relaxants studied. This potentiation was equal for tubocurarine and metocurine, but less for pancuronium. PMID- 2892912 TI - Enhancement of jejunal and colonic absorption of fosfomycin by promoters in the rat. AB - A means of enhancing absorption of the antibiotic, fosfomycin, has been investigated using promoters in rat jejunum and colon. Polyoxyethylene lauryl ether (BL-9EX), saponin, the sodium salts of fatty acids and mixed micelles were effective at 1% in increasing fosfomycin absorption. Of the sodium salts of saturated medium-chain fatty acids examined, the strength of this effect was in the order caprate greater than laurate greater than caprylate. Mixed micelles, consisting of fusogenic lipids and sodium taurocholate, enhanced fosfomycin absorption independently of the degree of unsaturation of the lipids; their effectiveness far exceeded that of sodium taurocholate alone. The action of these promoters was more evident in the colon than in the jejunum, except for the sodium salts of bile acids and disodium ethylenediaminetetraacetate (EDTA-2Na). The effects of glycocholate and taurocholate were essentially the same at both absorption sites, but that of EDTA-2Na was much greater in the jejunum than the colon. Improved fosfomycin absorption was observed at more than 0.5% sodium caprate concentrations in both the jejunum and colon. BL-9EX was effective at 0.1% in the jejunum or at 0.05% in the colon. The effectiveness at these low concentrations demonstrates the practicality of promoters for improving fosfomycin absorption with only minor membrane damage, especially in the colon. PMID- 2892914 TI - Eating caused by neuropeptide-Y injection in the paraventricular hypothalamus: response to (+)-fenfluramine and (+)-amphetamine in rats. AB - (+)-Fenfluramine and (+)-amphetamine have been compared for their ability to reduce food intake in food-deprived rats or eating caused by injecting neuropeptide-Y in the paraventricular hypothalamus of free feeding rats. (+) Fenfluramine at doses ranging from 0.625 to 5 mg kg-1 reduced eating caused by neuropeptide-Y more effectively than it did the food intake of food-deprived rats, whereas (+)-amphetamine (dose range 0.625-2.5 mg kg-1) reduced both types of eating to a similar extent. The results confirm that (+)-fenfluramine, although less potent than (+)-amphetamine in reducing eating by food-deprived rats, markedly reduces overeating caused by various endogenous substances or stress in free feeding rats. The physiological significance of the neuropeptide-Y induced eating and its control by (+)-fenfluramine remains to be elucidated. PMID- 2892915 TI - Influence of the new antihypertensive drug, SM-2470 (a quinazoline derivative), on cholesterol metabolism in rats. AB - The influence of SM-2470 (4-amino-2-(4-[bicyclo(2,2,2)oct-2-ene-5-carbonyl]-1 piperazinyl)- 6,7-dimethoxyquinazoline), a new antihypertensive agent, on cholesterol metabolism was investigated in hypercholesterolaemic rats, using the dual isotope method (cholesterol absorption) and the intestinal ligated loop method (cholesterol uptake). In the hypercholesterolaemic model, 1-30 mg kg-1 doses of SM-2470 significantly inhibited the elevation of the total serum cholesterol and very low and low density lipoproteins (VLDL + LDL)-cholesterol, without causing any change in the hepatic cholesterol level. In a dual isotope model experiment, SM-2470 (10, 30 mg kg-1) inhibited the intestinal absorption of cholesterol, but did not affect biliary excretion of sterol and/or bile acids, nor did it affect cholesterol movement from the liver to blood. In the intestinal ligated loop method, SM-2470 remarkably inhibited the mucosal uptake of cholesterol in a dose-dependent manner in 0.5-2.0 mg mL-1 of micellar solution. In addition, SM-2470 inhibited micellar formation in-vitro, which increased the distribution of large sized micelles as well as cholesterol absorption inhibitors. From these results, it can be assumed that a possible mechanism behind the hypocholesterolaemic effect of SM-2470 is the inhibition of cholesterol absorption related to the reduction of cholesterol solubilization, occurring in the gut micelles, similar to the action of plant sterol. PMID- 2892916 TI - Selective agonists and antagonists for 5-hydroxytryptamine receptor subtypes, and interactions with yohimbine and FG 7142 using the elevated plus-maze test in the rat. AB - The effects of some 5-HT receptor ligands were investigated on measures of anxiety in an elevated plus-maze test in the rat. Quipazine (2 and 4 mg kg-1), a non-specific 5-HT agonist and ritanserin (0.25-10 mg kg-1), a 5-HT2 receptor antagonist displayed anxiogenic profiles by reducing both of the measures of anxiety used in this test. Two 5-HT1A receptor ligands, buspirone (4 and 8 mg kg 1) and ipsapirone (2.5-10 mg kg-1) and the 5-HT1 agonist, RU 24969 (0.1875-1.5 mg kg-1) significantly reduced only the percentage of time spent on the open arms. ( )-Propranolol (5 and 10 mg kg-1), a 5-HT1 receptor antagonist significantly reduced only the percentage of entries made onto the open arms. Metergoline (4 mg kg-1), a non-specific 5-HT antagonist displayed anxiolytic effects in this test by increasing both measures of anxiety. The 5-HT1A receptor agonist, 8-OH-DPAT (0.0625-0.25 mg kg-1) had no effect on either of the measures of anxiety. The results from the non-specific ligands (quipazine and metergoline) are consistent with the theory that a reduction in 5-HT function reduces anxiety. However, in spite of their more selective effects on 5-HT receptors the results in this test from the more specific ligands are not consistent with a strong involvement of any single receptor subtype. The interaction studies with yohimbine and FG 7142 (beta-carboline-3-carboxylate methylamide) provided no clear evidence for a major role of 5-HT pathways in the mediation of their anxiogenic effects. PMID- 2892917 TI - Pharmacokinetics of lisinopril (MK521) in healthy young and elderly subjects and in elderly patients with cardiac failure. AB - The pharmacokinetics of lisinopril were determined in 6 healthy young, 6 healthy elderly and 6 elderly patients with cardiac failure. Lisinopril (5 mg day-1) was administered for 7 days. Plasma lisinopril concentration was measured at 1, 2, 4, 6, 8 and 24 h on days 1 and 7 of the study. The two elderly groups had higher serum lisinopril concentrations than the healthy young subjects (P less than 0.05). There were no significant differences in any of the areas under the curve (AUC) for lisinopril plasma concentration (over time) between the healthy young and healthy elderly groups. The healthy young patients had AUC values on day 7 lower than elderly patients with cardiac failure (P less than 0.01). Creatinine clearance was correlated with lisinopril clearance (r = 0.63; P = 0.006) and with AUC on day 7 (r = -0.67; P = 0.004). Lisinopril clearance was different in the three groups (P less than 0.05): healthy young patients had the highest and elderly patients with cardiac failure the lowest values. Thus, in the elderly a reduced renal clearance of lisinopril leads to higher and more sustained blood levels. In elderly patients with cardiac failure, renal function should be estimated before lisinopril is prescribed as a reduction in dose may be appropriate. PMID- 2892918 TI - Nasal administration of desmopressin by spray and drops. AB - A solution of desmopressin was administered intranasally as a spray using a metered dose pump, or as drops using a single dose pipette or rhinyle catheter. Volunteers, and patients with diabetes insipidus, were given an intranasal dose of 20 micrograms desmopressin by each method. The antidiuretic activity was measured by determination of urine osmolality and diuresis. Each delivery system was equally effective in producing a rapid onset of activity, a highly reproducible magnitude of effect and duration of the antidiuretic effect which lasted for more than 8 h. The pipette and spray pump offer a choice of single dose administration without preservative, or for chronic use, well-controlled, reproducible dosing, respectively. PMID- 2892919 TI - Influence of pH on the buccal absorption of morphine sulphate and its major metabolite, morphine-3-glucuronide. AB - Buccal absorption of morphine sulphate and morphine-3-glucuronide at various buffer pH values (4 to 10) over 5 min has been investigated in seven and four normal healthy volunteers, respectively. Increasing pH caused an increase in buccal absorption of both. The maximum mean absorption was 37% at pH 10 for morphine and 19% at pH 8 for morphine-3-glucuronide. PMID- 2892920 TI - The effect of hydroxocobalamin on the nitroprusside-induced relaxation of rat aortic preparations. AB - Hydroxocobalamin (HOCb) when mixed with sodium nitroprusside (SNP) in a 10:1 or 1:1 molar ratio had no significant effect on the relaxation of noradrenaline precontracted rat aortic rings. However, the addition of HOCb did prolong the time taken for the relaxant response to occur. The time taken for a 0.34 microM SNP dose to exert 50% of its relaxant effect was increased by about 120 and 35% with 10:1 and 1:1 HOCb/SNP molar ratio mixtures, respectively. A 0.5:1 HOCb/SNP molar ratio mixture caused no prolongation. In incubations with [14C]SNP, it was found that mixing with equimolar, or greater, amounts of HOCb, reduced aortic tissue uptake of radioactivity. The results support the hypothesis that both SNP alone and SNP/HOCb complexes breakdown extracellularly to release the same amount of active species, but that in the case of the complexes the active agent is released at a slower rate. PMID- 2892921 TI - The separation of unbound prednisolone in plasma by centrifugal ultrafiltration. AB - To study variable plasma protein binding of prednisolone in children with nephrotic syndrome we have devised a simple rapid method for measuring unbound prednisolone. The plasma was initially ultrafiltered at 37 degrees C fixed angle head at 1500 g for 30 min then the filtrate was analysed by high pressure liquid chromatography. The effects of variable ultrafiltration conditions were studied. The method was used to compare the AUC unbound prednisolone in a nephrotic child (plasma albumin concentration 18 g L-1) with a control (plasma albumin concentration 43 g L-1); their respective AUC unbound prednisolone values were 4.02 mg h L-1 and 1.07 mg h L-1. PMID- 2892922 TI - Effect of trimethoprim, paracetamol and cimetidine on trimetrexate metabolism by rat perfused isolated livers. AB - Trimetrexate (TMTX), a non-classical antifolate, is currently in clinical trial as an antineoplastic drug. In the rat perfused isolated liver, it undergoes extensive metabolism to two metabolites, M1 and M2, which are excreted primarily in the bile. The metabolites result from demethylation, and M1 is also glucuronidated. We examined the effects of three commonly used drugs on the elimination of 1 mg of TMTX by the rat perfused isolated liver (perfusate volume was 100 mL). Co-administration of either 1 or 5 mg cimetidine, a well-known inhibitor of microsomal oxidation, caused an increase in TMTX terminal elimination half-life (69 and 100% at 1 and 5 mg, respectively) and a decrease in clearance (40 and 46% at 1 and 5 mg, respectively). Paracetamol (acetaminophen) was chosen for a possible interaction with TMTX because its major metabolic pathway is glucuronidation. Five mg paracetamol resulted in no change in TMTX pharmacokinetics, but M1 concentrations were increased by 72% in bile, and M2 was not present in perfusate. The third drug tested was trimethoprim, which has some structural similarities to TMTX; however, no effects were noted on the levels of TMTX, M1 or M2 after 1 mg trimethoprim. These results indicate that TMTX elimination can be inhibited by cimetidine, probably due to competition for microsomal enzymes, and that paracetamol may alter the metabolite profiles; trimethoprim had no effect on TMTX disposition under the conditions employed. PMID- 2892923 TI - Cross-tolerance development to the prolongation of pentobarbitone-induced sleep by delta 8-tetrahydrocannabinol and 11-hydroxy-delta 8-tetrahydrocannabinol in mice. AB - Repeated administration (5 mg kg-1 day-1 i.v.) of delta 8-tetrahydrocannabinol and its active metabolite, 11-hydroxy-delta 8-tetrahydrocannabinol caused tolerance to develop to their prolonging effect on pentobarbitone-induced sleep in mice. Reciprocal cross-tolerance also developed after seven daily doses of these cannabinoids. The magnitude of the tolerance developed by the metabolite was greater than that by delta 8-tetrahydrocannabinol. The results suggest that 11-hydroxy-delta 8-tetrahydrocannabinol plays an important role both in the sleep prolonging effect of delta 8-tetrahydrocannabinol and its tolerance development. PMID- 2892924 TI - Effects of three new anthracyclines and doxorubicin on the rat isolated heart. AB - The acute cardiac toxicity of three second-generation anthracycline analogues and doxorubicin was compared in a model of the rat isolated Langendorff perfused heart. The drugs, doxorubicin (DX), 4-epi-doxorubicin (4'EDX), 4-demethoxy daunorubicin (4DMDR) and 4'-deoxy-doxorubicin (4'dxDX) were infused for 40 min at a concentration of 26 microM into the isolated hearts. All four compounds significantly reduced cardiac work and its first derivative. The time to 50% decrease in work (TW50) was respectively 36, 23, 9 and 7 min for DX, 4'EDX, 4'dxDX and 4DMDR. The three anthracycline derivatives, but not DX, significantly increased coronary resistance. Heart rate was reduced by all compounds compared with baseline, but not compared with controls. Rhythm disturbances were seen with all five hearts perfused with 4DMDR, which stopped beating before 40 min; 2/5 hearts in the 4'EDX group and 1/5 hearts in the 4'dxDX group also stopped before the end of perfusion. All the compounds reached concentrations in the myocardium 8 to 50 times higher than in the perfusing medium. The more cardiotoxic the compound, the higher was its myocardial concentration; a significant correlation was found for all four agents. Noradrenaline was never measurable in the perfusate of control and DX hearts; perfusion with the three anthracycline derivatives caused some release, but the pattern was not clearcut and the maximum concentrations attained in the perfusate were relatively low (less than or equal to 1.6 X 10(-9) M). In conclusion, in the rat isolated perfused heart, the early cardiotoxicity induced by equimolar concentrations of the three anthracycline compounds was greater than that induced by DX and was directly related to drug accumulation in the myocardium. Catecholamines do not seem to have a major role in the development of toxicity in this model. PMID- 2892925 TI - Extraordinary postmortem stability of kappa opioid receptors in guinea-pig brain. AB - Postmortem delay can be an important variable in biochemical studies on autopsy tissue. We subjected guinea-pig brains to gradual cooling, simulating temperature conditions of human postmortem brains, in order to assess the sensitivity of kappa receptors to postmortem degradation. Kappa receptor specific binding was defined as the (-)-[3H]ethylketocyclazocine bound in the presence of 100 nM D ala2-D-leu5-enkephalin and 30 nM morphine. Postmortem delays of up to 16 h did not alter the affinity or density of kappa binding sites. The remarkable stability of kappa receptors may greatly facilitate the study of this opioid receptor subtype in human brain. PMID- 2892926 TI - The effects of 17 beta-oestradiol or testosterone on the response to S-warfarin in castrated male rats. AB - The effects of castration alone, or followed by administration of 17 beta oestradiol or testosterone, on the action of S-warfarin have been investigated in male Wistar rats castrated at 4 weeks of age. Six to 10 weeks later, blood samples were taken before, and at 24 h and 7 days after onset of administration of either 17 beta-oestradiol (50 to 500 micrograms kg-1 day-1 i.p.), testosterone (500 micrograms kg-1 day-1 i.p.), or vehicle (polyethylene glycol 200 i.p.). On the seventh day of these interventions, S-warfarin (6.3 mg kg-1 i.p.) was given; prothrombin complex activity (PCA) was then measured over the next 72 h. In addition, a group of sham-operated rats were given S-warfarin, alone. The control prothrombin times were lower in castrated rats (17.9 +/- 0.4 s) than in sham operated rats (19.1 +/- 0.6 s). Warfarin, over the first 24 h of its administration, caused a significant (P less than or equal to 0.01) fall in PCA in each group of rats, the fall in PCA in castrated rats pretreated with vehicle being significantly (P less than or equal to 0.05) less than that seen in the sham-operated rats. The fall was the same in castrated rats given vehicle or those given 17 beta-oestradiol. In contrast, warfarin caused a greater fall in PCA in the presence of testosterone than in the other groups of castrated rats. PMID- 2892927 TI - Temperature dependence of M pilus formation as demonstrated by electron microscopy. AB - The formation of IncM plasmid encoded pili is dependent on the incubation temperature of the corresponding host strains. By labelling the short, rigid M pili with the donor specific bacteriophage luminal diameter M, the presence of pili at 30 degrees C but not at 37 degrees C incubation temperature could be demonstrated for E. coli K12 substrains carrying different IncM group plasmids. In contrast, such a temperature dependence of M pilus formation is not observed in S. typhimurium substrains. PMID- 2892928 TI - Reflex pressor response to gastric mechanical stimulation in rats. AB - Neural and humoral mechanisms involved in the reflex pressor response during mechanical stimulation of the stomach of rats were investigated. The arterial blood pressure response was prevented by inhibition of alpha-adrenergic vasoconstriction using either an alpha-adrenergic blocker or a ganglionic blocker. In addition, there was a small decrease in the response after nephrectomy. However, there were no alterations in the response after beta adrenergic blockade, bilateral adrenalectomy, inhibition of converting enzyme activity with enalapril or bilateral cervical vagus nerve transection. The heart rate was not modified after either intervention. After vagotomy the time of recovery of the basal blood pressure was significantly prolonged. It can be concluded that the blood pressure response to mechanical stimulation of the stomach wall is of neural rather than of humoral origin and mainly involves activation of alpha-adrenergic receptors. Vagal efferent pathways could be also involved. PMID- 2892929 TI - Effect of cryptorchidism on steroidogenic and mitogenic activities in rat testicular interstitial fluid. AB - There was a significant (P less than 0.05) and consistent increase in the potency of steroidogenic stimulatory activity (testosterone production by purified Leydig cells in vitro) in testicular interstitial fluid of the cryptorchid compared to the scrotal testis from 1 to 4 weeks after the induction of unilateral cryptorchidism. In contrast, the level of mitogenic activity [( 3H]thymidine incorporation into 3T3 cells) was not significantly different between interstitial fluid from cryptorchid and scrotal testes for up to 4 weeks after surgery. These results indicate that the steroidogenic activity and the mitogenic activity are due to different, as yet unidentified, factors in testicular interstitial fluid. PMID- 2892930 TI - Transcutaneous electrical nerve stimulation for reducing narcotic use after cesarean section. AB - This study evaluated the potential efficacy of transcutaneous electrical nerve stimulation in reducing narcotic requirements following cesarean section. The total required dose of postoperative analgesic (meperidine) was found to be 511 mg in the experimental group and 456 mg in the control group. There was no significant difference in narcotic use or hospital stay between the experimental and control groups. PMID- 2892931 TI - Correlation of angiographic abnormalities with disease manifestations and disease severity in polyarteritis nodosa. AB - We evaluated angiograms of 26 patients with polyarteritis nodosa (PAN) as well as the associated clinical and laboratory features. All patients had visceral angiograms and either biopsy or angiographic proof of PAN. Severe disease was defined as central nervous system PAN, renal failure requiring dialysis, gangrene of fingers or toes, cardiomyopathy, bowel infarction, hepatic failure, or hepatic infarction. The presence of aneurysms was associated with severe hypertension, hepatitis B surface antigenemia and clinically severe disease. Angiography may therefore identify a subset of patients with more severe involvement and may be of value in management decisions. PMID- 2892932 TI - Conformational analysis and structural comparisons of (1R,3S)-(+)- and (1S,3R)-( )-tefludazine, (S)-(+)- and (R)-(-)-octoclothepin, and (+)-dexclamol in relation to dopamine receptor antagonism and amine-uptake inhibition. AB - Conformational analysis with molecular mechanics (MM2(85] and molecular superimposition studies of (1R,3S)-(+)- and (1S,3R)-(-)-4-[3-(4-fluorophenyl)-6 (trifluoromethyl)indan-1-yl]-1- piperazineethanol (tefludazine) and (S)-(+)- and (R)-(-)-octoclothepin have been employed to identify biologically active conformations of these compounds with respect to dopamine receptor antagonism and amine-uptake inhibition. In contrast to what is commonly assumed, these studies indicate that the conformation of (S)-(+)-octoclothepin responsible for the dopamine receptor antagonism is different from the one observed in the crystal. From least-squares molecular superimpositions with the potent and stereoselective dopamine receptor antagonist (1R,3S)-tefludazine, biologically active conformations for the two compounds on the dopamine receptor have been deduced. This analysis also rationalizes the enantioselectivity of octoclothepin on the dopamine receptor. The X-ray structure of (S)-(+)-octoclothepin is shown to correspond structurally to the 1S,3R enantiomer of tefludazine, which is an amine uptake inhibitor. This correspondence provides a structural basis for the norepinephrine (NE) uptake blocking properties of octoclothepin. It is predicted that the enantioselectivity of the NE-uptake inhibition of octoclothepin should be low with the S-(+) enantiomer as the more active optical isomer. A comparison of the deduced biologically active conformation of (S)-(+)-octoclothepin with (+) dexclamol is also discussed on the basis of earlier derived superimposition studies with (+)-dexclamol. PMID- 2892933 TI - (Acyloxy)alkyl carbamates as novel bioreversible prodrugs for amines: increased permeation through biological membranes. AB - (Acyloxy)alkyl carbamates of the type R1R2N-CO-O-CHR3-OCO-R4 are described as novel bioreversible prodrugs for primary and secondary amines. These were prepared either by a one-step reaction involving nucleophilic attack on p nitrophenyl alpha-(acyloxy)alkyl carbonates with displacement of p-nitrophenol or by reaction of alpha-haloalkyl carbamates with silver or mercury salts of carboxylic acids. Enzymatic hydrolysis of the ester bond in these ester carbamates leads to a cascade reaction resulting in rapid regeneration of the parent amine. Permeability measurements of such nonionic derivatives of atenolol, betaxolol, pindolol, propranolol, and timolol through fuzzy rat skin and rabbit cornea mounted on diffusion cells show that derivatization of the hydrophilic beta-blockers results in several-fold increase in permeation through these biological membranes. However, prodrug modification of the lipophilic beta blockers leads to little advantage in permeability characteristics. PMID- 2892934 TI - Design and synthesis of a series of combined vasodilator/beta-adrenoceptor antagonists based on 6-arylpyridazinones. AB - A series of new 6-[4-[[(aryloxy)acyl]amino]phenyl]-4,5-dihydropyridazinones have been synthesized and evaluated as combined vasodilator/beta-adrenoceptor antagonists and potential antihypertensive agents. Many of the early compounds displayed an unacceptably high level of intrinsic sympathomimetic activity (ISA) and a relatively short duration of action. Disubstitution in the 2,3-positions or in the 4-position of the aryloxy ring gave compounds with low ISA levels and, in some instances, improved duration of action. All of the compounds were vasodilators, but the 5-methylpyridazinone derivatives showed consistently greater antihypertensive activity than their 5-H lower homologues. Further detailed pharmacological investigations led to the selection of 6-[4-[3-[[2 hydroxy-3-[4-[2- (cyclopropylmethoxy)ethyl]phenoxy]propyl]amino]propionamido] phenyl]- 5-methyl-4,5-dihydro-3(2H)-pyridazinone (4t) (SK&F 95018) as a development candidate. PMID- 2892935 TI - Synthesis and biological activity of the four stereoisomers of 6-[4-[3-[[2 hydroxy-3-[4-[2- (cyclopropylmethoxy)ethyl]phenoxy]propyl]amino]-propionamido] phenyl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone, a combined vasodilator and beta adrenoceptor antagonist. AB - 6-[4-[3-[[2-Hydroxy-3-[4-[2- (cyclopropylmethoxy)ethyl]phenoxy]propyl]amino]propionamido] phenyl]- 5-methyl 4,5-dihydro-3(2H)-pyridazinone (3) consists of a mixture of four stereoisomers, i.e., two racemates, as a consequence of the two asymmetric centers contained in the structure. An approximately equimolar mixture of these two racemates exhibits a novel combination of vasodilation and beta-adrenergic antagonist activity. This paper describes the synthesis of each of the four possible stereoisomers of 3 and provides clear evidence for the different pharmacological profile of each of the stereoisomers. The RA,SB isomer 3a has an overall profile slightly better than the complete mixture; the other three isomers all show reduced activity as vasodilators and/or beta-adrenergic antagonists. PMID- 2892936 TI - Synthesis and potential antipsychotic activity of 1H-imidazo[1,2-c]pyrazolo[3,4 e]pyrimidines. AB - The synthesis of a series of 1H-imidazo[1,2-c]pyrazolo[3,4-e]pyrimidines is reported along with the effects of these compounds in preclinical tests for antipsychotic activity. Certain of these compounds displayed antipsychotic-like effects in conditioned avoidance tests, but unlike currently used antipsychotic drugs, they did not have affinity for brain dopamine receptors. These compounds also did not cause dystonias predictive of extrapyramidal side effects in monkeys at doses that produced behavioral effects. On the basis of this unique biological profile, a member of this series 7,8-dihydro-8-ethyl-1,3,5-trimethyl-1H imidao[1,2-c]pyrazol[3,4-e] pyrimidine (19, CI-943), has been selected for clinical evaluation as an antipsychotic agent. PMID- 2892937 TI - 4-N-hydroxy-L-2,4-diaminobutyric acid. A strong inhibitor of glutamine synthetase. AB - Analogues of glutamic acid were synthesized and evaluated for their inhibitory activity toward glutamine synthetase (EC 6.3.1.2; GS). The title compound, 4-N hydroxy-L-2,4-diaminobutyric acid (NH-DABA), showed a potent inhibitory activity against GS from both sheep brain and soybean. The inhibition is competitive with respect to glutamic acid and the Ki values of sheep brain GS and soybean GS for NH-DABA are 0.007 mmol and 0.021 mmol, respectively. The activity of inhibition is comparable to those of L-methionine sulfoximine and 2-amino-4-(hydroxymethyl phosphinyl)butyric acid (phosphinothricin). PMID- 2892938 TI - Cytogenetic and molecular studies of trisomy 13. AB - Chromosome heteromorphisms, restriction fragment length polymorphisms, or both were used to study the parental origin of 33 cases of simple trisomy 13 and eight cases of translocation trisomy 13. The most common origin for the simple trisomies was non-disjunction at maternal meiosis I, while for the translocations an equal number of paternally and maternally derived cases was observed. In seven of the simple trisomies, information was obtained from both the cytogenetic and molecular markers, making it possible to study recombination between the two non disjoined chromosomes. Five of the seven cases involved errors at meiosis I, with crossing over being detected in two of three cases of maternal origin and in one of two cases of paternal origin. This indicates that absence of recombination because of pairing failure is unlikely to be of major importance in the genesis of trisomy 13. PMID- 2892939 TI - Non-deletion haemoglobin H disease in Papua New Guinea. AB - Analysis of DNA from members of a Melanesian family from Papua New Guinea with haemoglobin (Hb) H disease revealed that all four alpha globin genes are intact in affected subjects. Study of restriction enzyme site and length polymorphisms and the use of oligonucleotide probes indicated that the molecular basis of this Papuan form of non-deletion Hb H disease differs from the previously described Middle Eastern and Mediterranean types. PMID- 2892940 TI - Potential dependence of the "electrically silent" anion exchange across the plasma membrane of Xenopus oocytes mediated by the band-3 protein of mouse red blood cells. AB - Mouse erythroid band-3 protein was incorporated into the plasma membrane of Xenopus oocytes by microinjection of poly(A)+-mRNA from spleens of anemic mice. Subsequently, the efflux of microinjected 36Cl was continuously followed in single oocytes in a perfusion chamber the bottom of which was formed by the window of a Geiger-Muller tube. During the flux measurements, the membrane potential was clamped to different holding potentials. The efflux increased over the voltage range of -10 to -100 mV by a factor of about 1.5. Since the membrane potential cannot act as a driving force of anion exchange, it is suggested that the observed slight potential dependence is related to a recruitment of the anion loaded transport protein by the electrical field, thereby changing the steady state distribution between inwardly and outwardly facing anion binding sites of the transport molecules. The experimental data are discussed in terms of ping pong kinetics, assuming that the potential dependence is primarily due to an effect of the electrical field in the membrane on the rate-limiting interconversion of inwardly and outwardly oriented anion binding sites. The results are compatible with the assumption that in the oocyte membrane the substrate-loaded band-3 molecules are preferentially inwardly oriented, and that the transition from the inwardly to the outwardly oriented conformation is associated with a reorientation of an effective charge of 0.1 elementary charge. During progesterone-induced maturation of the oocytes, several endogenous transport systems change their activity drastically. The mouse band-3 protein in the oocyte membrane also undergoes activity changes; however, these changes do not seem to involve direct regulation by specific metabolic processes. They can be explained as a consequence of the depolarization of the membrane potential associated with the maturation process. PMID- 2892941 TI - Complete primary structure of vertebrate smooth muscle myosin heavy chain deduced from its complementary DNA sequence. Implications on topography and function of myosin. AB - The 1979 amino acid sequence of embryonic chicken gizzard smooth muscle myosin heavy chain (MHC) have been determined by cloning and sequencing its cDNA. Genomic Southern analysis and Northern analysis with the cDNA sequence show that gizzard MHC is encoded by a single-copy gene, and this gene is expressed in the gizzard and aorta. The encoded protein has a calculated Mr of 229 X 10(3), and can be divided into a long alpha-helical rod and a globular head. Only 32 to 33% of the amino acid residues in the rod and 48 to 49% in the head are conserved when compared with nematode or vertebrate sarcomeric MHC sequences. However, the seven residue hydrophobic periodicity, together with the 28 and 196 residue repeat of charge distribution previously described in nematode myosin rod, are all present in the gizzard myosin rod. Two of the trypsin-sensitive sites in gizzard light meromyosin have been mapped by partial peptide sequencing to 99 nm and 60 nm from the tip of the myosin tail, where these sites coincide with the two "hinges" for the 6 S/10 S transition. In the head sequence, several polypeptide segments, including the regions around the putative ATP-binding site and the reactive thiol groups, are highly conserved. These areas presumably reflect conserved structural elements important for the function of myosin. A multi-domain folding model of myosin head is proposed on the basis of the conserved sequences, information on the topography of myosin in the literature, and the predicted secondary structures. In this model, Mg2+ ATP is bound to a pocket between two opposing alpha/beta domains, while actin undergoes electrostatic interactions with lysine-rich surface loops on two other domains. The actin-myosin interactions are thought to be modulated through relative movements of the domains induced by the binding of ATP. PMID- 2892943 TI - Multidrug resistance. AB - The ability of malignant cells to develop resistance to cytotoxic drugs poses a major obstacle to the ultimate success of cancer therapy. While some mechanisms of resistance allow cells to survive exposure to a single agent, the phenomenon of multidrug resistance (MDR) confers upon cells the ability to withstand exposure to lethal doses of many structurally unrelated antineoplastic agents. MDR has been strongly linked to the overexpression of a membrane-associated glycoprotein, P-glycoprotein, which appears to play a role in drug efflux. However, several lines of evidence suggest that other mechanisms of resistance are involved in MDR; biochemical similarities observed in a human breast cancer cell line after the acquisition of MDR and in carcinogen-induced rat preneoplastic hepatic nodules indicate that changes in regulation of phase I and phase II drug-metabolizing enzymes may also play a role in MDR. An atypical pattern of MDR has been characterized and related to altered topoisomerase activity. Improvement in current cancer chemotherapy may be achieved by interfering with the regulation and expression of mechanisms of MDR. PMID- 2892944 TI - The effects of beta-adrenergic blockade on serum phosphate and plasma catecholamines after high-energy missile trauma. PMID- 2892942 TI - Arrhythmogenic action of alpha 1-adrenoceptor stimulation in normoxic rat ventricular myocardium: influence of nisoldipine, reduced extracellular Ca2+ and ryanodine. AB - This study examines the arrhythmogenic action of alpha 1 and alpha 2-adrenoceptor stimulation in the isolated perfused rat heart. The alpha 1-agonist methoxamine in the presence of the beta 1-antagonist atenolol 10(-6) M decreased the ventricular fibrillation threshold in the normoxic rat ventricular myocardium: VFT values (mA): Control 11.2 +/- 0.5; methoxamine 10(-6) M 4.9 +/- 0.9 (P less than 0.01 vs control); methoxamine 10(-5) M 3.5 +/- 0.5 (P less than 0.01 vs control). The alpha 1-antagonist prazosin 10(-8) M prevented the methoxamine induced fall in ventricular fibrillation threshold. The alpha 2-agonist BHT 933 (azepexole) in the presence of atenolol 10(-6) M produced no alteration in the ventricular fibrillation threshold. Methoxamine 10(-6) M to 10(-5) M had a positive inotropic effect with increased left ventricular pressure development, myocardial oxygen consumption and QT-interval; however, tissue levels of cyclic AMP remained unchanged. Methoxamine 10(-6) M did not alter heart rate, coronary flow rate or deplete tissue levels of adenosine triphosphate, phosphocreatine or glycogen. The enhanced vulnerability to ventricular fibrillation induced by methoxamine could be demonstrated only at supraphysiological extracellular calcium concentrations (2.5 mM) but not at physiological calcium concentrations (1.25 mM). The arrhythmogenic and inotropic effect of methoxamine 10(-6) M was prevented by inhibition of transsarcolemmal Ca2+ ion influx by nisoldipine 10(-8) M or by inhibition of release of Ca2+ from sarcoplasmic reticulum by ryanodine 10(-9) M to 10(-8) M. Thus in isolated normoxic rat heart preparations, activity of the alpha 1-receptor appears to mediate ventricular arrhythmogenesis but only in the setting of myocardial calcium overload. The arrhythmogenic effect of alpha 1-stimulation may be due to increased transsarcolemmal calcium influx and enhanced release of calcium from the sarcoplasmic reticulum; increased myocardial oxygen consumption secondary to greater left ventricular pressure development may contribute in part. PMID- 2892945 TI - Re: Association between abdominal wall defects and cryptorchidism. PMID- 2892946 TI - The role of epinephrine as a neuromodulator in spontaneously hypertensive rats. AB - The present study was carried out to elucidate the role of epinephrine as a neuromodulator in hypertension. The effects of epinephrine on norepinephrine release from the sympathetic nerve endings were examined in isolated perfused mesenteric arteries of spontaneously hypertensive rats (SHR) and age-matched Wistar Kyoto rats (WKY). Norepinephrine overflow during electrical nerve stimulation (5, 15 Hz) was significantly greater in SHR than in WKY. Low concentration of exogenous epinephrine (5.5 X 10(-9) M) potentiated norepinephrine overflow during nerve stimulation in SHR, and this (at 15 Hz stimulation) was antagonized by propranolol (5.0 x 10(-7) M), whereas, the overflow in WKY was reduced by the same concentration of epinephrine. A higher concentration of epinephrine (1.4 x 10(-8) M) decreased norepinephrine overflow in both SHR and WKY, and this change (at 15 Hz stimulation) was antagonized by yohimbine (1.0 x 10(-7) M). Further, magnitudes of the suppressions were smaller in SHR than in WKY. These results suggest that altered modulations of norepinephrine release by epinephrine through presynaptic beta- and alpha 2 adrenoceptors might induce increased sympathetic nerve activity in SHR. PMID- 2892947 TI - [Hemodynamics during coronary revascularization in patients receiving beta adrenergic blocking drugs]. PMID- 2892948 TI - [Cytogenetic study of adult T-cell leukemia]. PMID- 2892949 TI - [Relationship between the clinical subtype and Epstein-Barr virus specific antibodies in patients with adult T-cell leukemia]. PMID- 2892950 TI - [Long-term remission in a case of acute adult T cell leukemia]. PMID- 2892951 TI - [A chronic type of adult T-cell leukemia accompanied by generalized cytomegalovirus infection]. PMID- 2892952 TI - [Amino acid neurotransmitters]. PMID- 2892953 TI - [Pharmacology of the brain]. PMID- 2892954 TI - [Physiopathologic chemistry of the schizophrenic brain]. PMID- 2892956 TI - [Urinary parameters for nephropathy]. PMID- 2892955 TI - [Internal neurology--a. Trends in the study of dementia and cerebrovascular disorders]. PMID- 2892957 TI - The transmitter role of glutamate in nervous systems. AB - Acceptance of L-glutamate as an excitatory transmitter was relatively slow compared to other transmitters, such as GABA. However, the transmitter role of L glutamate has received more attention recently. In the crustacean neuromuscular junction L-glutamate fulfills most of the criteria for the transmitter identification. Studies on the glutamate receptor antagonist suggest that L glutamate may also be the transmitter at the squid giant synapse. L-Glutamate may be the excitatory transmitter in many parts of CNS, although the evidence for this hypothesis is still not complete. The role of L-aspartate as the transmitter in CNS is not clear but its contribution may be less than that of L-glutamate. Glutamate receptors have been classified into three groups according to pharmacological properties. However, recent observations suggest that the situation seems more complicated than previously expected and more detailed comparison between synaptic potentials and glutamate action is needed. PMID- 2892958 TI - Enzyme-linked immunosorbent assay for detection of antibody against hemorrhagic fever with renal syndrome virus in sera from experimentally infected rats. PMID- 2892959 TI - A new type of Robertsonian translocation (1/26) in a bull with unilateral cryptorchidism, probably occurring de novo. PMID- 2892960 TI - Population shift from piliated to non-piliated bacteria in kidneys, bladder and urine of mice infected with Corynebacterium renale strain No. 115 piliated bacteria. PMID- 2892961 TI - Quantitative and qualitative studies of antibody-induced mesangial cell damage in the rat. AB - Intravenous administration of heterologous anti-rat thymocyte serum (ATS), which reacts with a Thy-1-like antigen present on rat glomerular mesangial cells, caused lytic (1 hr to 2 days), hypercellular (4 to 14 days), and sclerotic (2 to 3 months) mesangial lesions in Lewis rats. The normal control of 48.6 +/- 7.9 (mean +/- SD) glomerular nuclei on histologic section decreased significantly (P less than 0.001) to 39.8 +/- 6.1, 37.4 +/- 6.0, and 38.9 +/- 6.8 at one hour, four hours and two days after ATS administration, respectively. Thereafter glomerular nuclei increased to 54.7 +/- 11.5 (P less than 0.05) at four days, 62.5 +/- 9.6 (P less than 0.001) at one week and 64.1 +/- 14.2 (P less than 0.001) at two weeks, and normalized (P greater than 0.05) to 49.4 +/- 8.9 at one month and 50.6 +/- 9.0 at three months. By electron microscopy, glomerular damage in the lytic stage was restricted to mesangial cells and was manifested as hydropic degeneration or lysis. Rabbit IgG and rat C3 were found in the mesangium one hour after injection; they decreased at two days and were negligible at four days. By paired label isotope study, 11.6 micrograms of antibody bound per 7.6 X 10(4) glomeruli at one hour was needed to induce mesangial cell degeneration. No or only minimal changes in proteinuria and in serum creatinine were observed with the dosage used in this rat strain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892962 TI - [The picture of acute abdomen in hemorrhagic fever with renal syndrome]. PMID- 2892964 TI - [Characteristics of the pharmacodynamics of alpha adrenergic receptor blockader pratsiol in various age groups]. PMID- 2892963 TI - [Changes in lung function following administration of eyedrops containing timolol, metipranolol, pindolol and pilocarpine in healthy probands and patients with mild bronchial asthma]. AB - Lung function was studied double blind and randomized in 5 patients with mild asthma bronchiale and 10 normal adults before and 30, 60 and 90 minutes after one drop of 0.5% Timolol, 0.6% Metipranolol or 0.9% NaCl in each eye. In the asthmatics bronchoconstriction was seen after both beta-receptor blocking agents, more pronounced after Timolol than after Metipranolol. There was a decrease in the forced expiratory volume in one second (FEV1.0) of 32, respectively 18%. No changes were observed in the normal subjects. In a separate study no significant changes were seen in the mean values of 10 other asthmatic subjects after 1% Pindolol, 3% Pilocarpin or 0.9% NaCl. However, in two patients FEV1.0 was reduced by 15% and 20% of the control values after applying Pindolol. In summary, not only beta-receptor-blocking agents without ISA produce a bronchoconstriction in asthmatic subjects, but also beta-blocker with ISA in individual cases. PMID- 2892965 TI - [Laser therapy]. PMID- 2892966 TI - [Effect of M-cholinolytics and histamine H2 receptor blockaders on the acid peptide factor in patients with peptic ulcer]. PMID- 2892967 TI - [Somatostatin]. PMID- 2892968 TI - The analysis of several nonopiate narcotic analgesics and cocaine in serum using high-performance liquid chromatography. AB - This paper describes a procedure for the quantitative determination of methadone, meperidine, normeperidine, pentazocine, propoxyphene, norpropoxyphene, and dextromoramide in serum down to levels of 10 micrograms/L and of cocaine down to 25 micrograms/L. The procedure involves a simple extraction technique and high performance liquid chromatography and is suitable for use in overdose drug screening, forensic toxicology, therapeutic drug monitoring, and pharmacokinetic studies. PMID- 2892970 TI - The effects of verapamil on left ventricular function in the presence of beta adrenergic blockade. AB - Supraventricular tachyarrhythmias frequently complicate myocardial revascularization. Intravenous administration of verapamil has been effective in terminating these arrhythmias. To determine the effects of verapamil on left ventricular systolic function, we implanted ultrasonic dimension transducers in dogs and, after they had recovered from the operation, studied them while they were awake and unsedated. Intravenous administration of verapamil (0.2 mg/kg) resulted in an elevation of cardiac output above baseline because of reflex induced tachycardia. Contractility, as measured by the load-independent end systolic pressure-volume relationship, remained unchanged. When the animals were pretreated with atropine and propranolol, verapamil resulted in a fall in cardiac output and contractility. The intact animal responded to the vasodilatory effect of verapamil by releasing catecholamines to maintain cardiac output and hemodynamic stability. Only when this compensatory mechanism was blocked by a beta-adrenergic blocker do the inherently negative inotropic and chronotropic effects of verapamil become apparent. The clinical ramifications of this finding are of greater importance to the surgeon as more patients receive beta-adrenergic blocking agents up to the time of the immediate preoperative period. We conclude that verapamil should be administered with caution to patients with supraventricular tachyarrhythmias who have been receiving beta-adrenergic blocking agents. PMID- 2892969 TI - Analysis of murine lymphocyte subpopulations by dual-color flow cytometry: technical considerations and specificities of monoclonal antibodies directed against surface markers. AB - We performed detailed phenotypic analysis of murine lymphocytes from thymus, spleen, lymph node, and peripheral blood using commercially available monoclonal antibodies, each with specificities for membrane surface markers and dual-color flow cytometry. Erythrocyte lysis techniques were utilized for lymphocyte preparation so that inherent difficulties with gradient techniques would be avoided, such as the potential for loss of abnormally sized cells. These studies demonstrated that the specificities of each monoclonal must be carefully determined; for example, the Lyt-1 monoclonal, frequently utilized to identify helper/inducer T cells, also reacts with suppressor/cytotoxic (Lyt-2+) cells; helper/inducer cells are better studied with a more recently available monoclonal, L3T4. Cells from different tissues may differ greatly not only in the presence of surface markers, but also in the surface density of each marker; this density can be studied and quantitated using appropriate analytic software. We also show that larger and more granular lymphocytes appear to be enriched for surface Ia antigen, indicating that these cells may be activated or regulatory subsets; these large, Ia+ T-cells will be lost from analysis if standard, narrow gate settings are used for analyzing forward and side-scatter characteristics or for cell sorting. PMID- 2892971 TI - Protection and expanded use of the left internal mammary artery graft by pericardial flap technique. AB - A pericardial flap can protect and enhance the use of the left internal mammary artery. The left free edge of the pericardium is sutured to the anterior chest wall, which protects the left internal mammary artery graft from lung encroachment and provides a more direct course. In our large experience, including several reoperations, no internal mammary artery was injured. PMID- 2892973 TI - [Interlocking medullary nailing in the management of septic pseudarthrosis of the long bones]. PMID- 2892972 TI - Side effects of therapeutic plasma exchange during treatment of polyarteritis nodosa. Comparison of filtration and centrifugation. 718 sessions in 63 patients. AB - Between 1981 and 1984, 72 patients (22-75 years) were included in a prospective study for treatment of Polyarteritis Nodosa (PN) which associated therapeutic plasma exchanges (TPE), corticosteroids (CS) 1 mg/kg/day, and a randomized trial of cyclophosphamide (CP) 2 mg/kg/day. We observed the incidence and analysed side effects (SE) occurring during TPE considering the technology of plasma removal. Full data were available for 63 patients. Seven hundred and eighteen TPE were performed. Centrifugation was used in 594 PE (82.7 per cent) with intermittent flow centrifugation (IFC) 320 times (44.5 per cent) and continuous flow centrifugation (CFC) 274 times (38.2 per cent). Filtration (F) was used in 124 sessions (17.3 per cent). Replacement fluid was 4 per cent albumin in 650 TPE and fresh frozen plasma (FFP) in 89 TPE. A total of two hundred and eleven SE were reported in 53 patients (84.1 per cent) during 173 TPE (24.1 per cent). Forty-six TPE were temporarily stopped because of SE (6.4 per cent). The mean volumes of removed plasma (ml/kg/TPE) were: 60.7 +/- 8.7 ml/kg when CFC was used 54.5 +/- 20 ml/kg with F and 52.5 +/- 9.6 ml/kg with IFC (n.s.) Main SE were: technical difficulties in 80 TPE, moderate or severe hypotension in 47, allergy to replacement fluid in 39. Hepatitis B antigen appeared in one patient. No death occurred during TPE and SE were usually minor and transient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2892975 TI - [Complex evaluation of the function of the hand]. PMID- 2892974 TI - [Management of pseudoarthrosis of the carpal navicular bone using Ender's small plate]. PMID- 2892976 TI - [Results of the surgical management of Dupuytren's contracture]. PMID- 2892977 TI - [Osteosynthesis using screws in fractures of the odontoid process. Preliminary report]. PMID- 2892978 TI - [Results of plastic repair of the acetabulum in childhood]. PMID- 2892979 TI - [The effect of immobilization on the connective tissue content and elasticity of muscles]. PMID- 2892980 TI - [Management of facial injuries in multiple trauma]. PMID- 2892981 TI - [Economic aspects of certain flexor tendon injuries]. PMID- 2892982 TI - [Plate osteosynthesis of mandibular fractures at a trauma center]. PMID- 2892983 TI - [Unstable epiphysiolysis fracture of the humerus in childhood]. PMID- 2892984 TI - Sexually dimorphic age-related differences in the immunocytochemical distribution of somatostatin in the platyfish. AB - Somatostatin (SRIF) was localized by immunocytochemistry in the brains and pituitary glands of male and female platyfish (Xiphophorus maculatus) between the ages of 8 and 30 months (average life span is 30 months). In the brain, immunoreactive (ir-) SRIF is found in the perikarya of the ventrobasal hypothalamus (nucleus lateralis tuberis, nucleus anterior tuberis), dorsomedial hypothalamus, dorsal thalamus, ventral tegmentum and rhombencephalic basal plate; in the pituitary it is localized surrounding the ir-growth hormone containing cells of the caudal pars distalis, and in older fish it is also found within certain cells of the pars intermedia. We have demonstrated that there are consistent, sexually dimorphic, age-related changes in the intensity and/or distribution of ir-SRIF. The sexual dimorphism of the changes in SRIF immunoreactivity during the aging of platyfish may be related to the different patterns of growth observed in males and females. PMID- 2892986 TI - Beta-adrenergic blockers. AB - beta-Adrenergic blocking drugs have been available for several years to treat ischemic heart disease and other cardiovascular and noncardiovascular disorders. There are multiple drugs in this class with various pharmacodynamic and pharmacokinetic properties that may be important in specific clinical situations and in avoiding certain adverse reactions. These drugs have been shown to be efficacious in relieving anginal symptoms and prolonging exercise tolerance, in reducing high blood pressure, for treating various arrhythmias, in therapy of hypertrophic cardiomyopathy, and for prolonging life in many survivors of acute myocardial infarction. PMID- 2892985 TI - Lymphokine-activated killer cells and aging in mice: significance for defining the precursor cell. AB - The present study was undertaken to define the cell populations which mediate lymphokine-activated killer (LAK) cell activity in mice. Because old mice exhibit markedly decreased to nondetectable natural killer (NK) cell activity, this age associated change provided an advantageous system to examine the contribution of NK and T cells to LAK activity. Spleen cells from either young (6-9 weeks) or old (20-26 months) mice were cultured with 1000 units/ml of recombinant interleukin 2 (rIL 2) for 3-5 days. The cells were then tested in a 51 Cr-release assay for their cytotoxicity against NK-resistant fresh tumor cells (MCA-102). The LAK activity exhibited by spleen cells from old mice following 5 days of culture was equivalent to that developed by spleen cells of young mice. This result was contrary to what would be anticipated if mature NK cells comprise the primary precursors of LAK activity, and required further elucidation. The Thy-1 and asialo GM1 (ASGM1) phenotypes of LAK precursor and effector cells were therefore examined by depletion techniques using the appropriate antibodies plus complement. The results using spleen cells harvested after 5 days of culture with rIL 2 showed that LAK effector cells which developed from spleen cells of both young and old mice were predominantly Thy-1+ (85.3% young; 91.8% old) and some coexpressed ASGM1. Spleen cells were treated prior to culture to study the precursor cells. Development of LAK activity by spleen cells from both young and old mice was greatly reduced by pretreatment with anti-ASGM1 plus complement. However, since spleen cells of old mice exhibit very low mature NK activity, these data suggest that the LAK precursors, at least in old mice, may be ASGM1+ NK precursor cells rather than mature ASGM1+ NK effector cells. In addition, treatment with anti-Thy-1 plus complement inhibited generation of a significant proportion of LAK activity only in the spleens of old mice, suggesting a qualitative difference in LAK precursor cells with age and supporting the heterogeneity of the cells which are capable of developing LAK activity. PMID- 2892987 TI - Predictive value of Glasgow coma score for awakening after out-of-hospital cardiac arrest. Cerebral Resuscitation Study Group of the Belgian Society for Intensive Care. AB - The Glasgow coma score (GCS) during days 1-6 after cardiac arrest was used to predict neurological outcome in 360 resuscitated victims of out-of-hospital cardiac arrest. A predictive rule based on the best GCS of 216 patients resuscitated in 1983-84 (prediction group) was constructed, and its predictive power was tested on 133 patients treated in 1985 (test group). Neurological outcome was correctly predicted 2 days after cardiac arrest in 80% of the prediction group, with a best GCS of 10 or above and 4 or below as cutoff points. For patients with a best GCS of 5-9, prediction of outcome was possible 6 days after cardiac arrest, with a best GCS of 8 during the first 6 days as the single cutoff point. The rule was then validated in the test group: the sensitivity was 96%; the specificity 86%; the negative predictive value 97%; and the positive predictive value 77%. These data suggest that this simple GCS-based rule can be helpful in predicting outcome in patients resuscitated after out-of-hospital cardiac arrest, but confirmation of these data is required in a prospective study in a larger number of patients. PMID- 2892988 TI - Effect of vitamin and mineral supplementation on intelligence of a sample of schoolchildren. AB - 90 schoolchildren aged twelve and thirteen years kept a dietary diary for three days. In most cases the average intake of vitamins was close to the recommended daily allowance, although for a minority the intake was low; with minerals the recommended daily allowance was less commonly achieved. To examine the possibility that deficiency of dietary minerals and vitamins was preventing optimum psychological function, a multivitamin/mineral supplement or a placebo was administered double-blind for eight months to 60 of the children. The supplement group, but not the placebo group or the remaining 30 who took no tablets, showed a significant increase in non-verbal intelligence. PMID- 2892989 TI - Prevention of steroid-induced osteoporosis with (3-amino-1-hydroxypropylidene) 1,1-bisphosphonate (APD). AB - In a prospective, randomised, placebo-controlled trial comparing the effect of (3 amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) (150 mg/day) plus calcium (1 g/day) with that of calcium alone on the bone mass of patients receiving long term glucocorticoid therapy, the mean metacarpal cortical area in patients receiving APD increased by 1.2% between 0 and 6 months (p less than 0.06) and then remained stable between 6 and 12 months. In contrast, this index progressively declined in the placebo group (p less than 0.05 at 12 months). The two groups differed significantly in the changes at both 6 and 12 months (p less than 0.01). Mean vertebral mineral density, as measured by quantitative computed tomography, increased by 19.6% over 12 months in the APD group (p less than 0.02) but showed a non-significant decline of 8.8% in controls. The differences between the changes were again significant (p less than 0.005). Biochemical indices and bone histomorphometry indicated a reduction in bone resorption and bone formation but there was no evidence of osteomalacia. APD may thus prevent bone loss in glucocorticoid-treated patients over a year. PMID- 2892991 TI - Placebo-controlled trial of topical interferon in labial and genital herpes. AB - The efficacy of topical interferon-beta (IFN-beta) treatment was assessed in 25 patients with herpes of the lips or genitals who completed a 2-year follow-up in a double-blind placebo-controlled trial. IFN-beta gel (10(5) U/g) 4 times daily (about 2 x 10(4) U) applied locally during eruptions (about 10 days) reduced the mean number of recurrences (p less than 0.007) and the duration of eruptions (p less than 0.007): in the placebo group these indices did not change significantly. Reduction of symptoms and severity was noted in 11 of 12 patients on IFN-beta and in only 1 on placebo. No important side-effects were recorded. Topical IFN-beta may therefore be advantageous as a time-limited local treatment of recurrent herpes simplex virus infections of the genitals and lips. PMID- 2892990 TI - Chronic enterovirus infection in patients with postviral fatigue syndrome. AB - 76 patients with the postviral fatigue syndrome (PVFS) and 30 matched controls were investigated. Virus isolation was attempted from concentrated faecal samples by direct culture and after acid dissociation of virus from antibody. Positive cultures of enteroviruses were obtained from 17 (22%) patients and 2 (7%) controls. An enterovirus-group-specific monoclonal antibody, 5-D8/1, directed against the VP1 polypeptide, was used to detect enteroviral antigen in the circulation, either free or complexed with antibody. VP1 antigen was detected in the serum of 44 (51%) of a further group of 87 PVFS patients. The number of patients positive for VP1 antigen was greater (42/44) when IgM complexes were detectable than when they were not (2/23). 1 year later, the 17 patients of the first group of 76 with positive cultures were again studied. The same virus was again isolated from 5 (29%), 13 (76%) had detectable IgM responses to enteroviruses, and 9 (53%) were positive for VP1 antigen in the serum. These results show that chronic infection with enteroviruses occurs in many PVFS patients and that detection of enterovirus antigen in the serum is a sensitive and satisfactory method for investigating infection in these patients. PMID- 2892992 TI - Back to the future--the reinvention of public health. PMID- 2892993 TI - When are cyclists going to wear helmets? PMID- 2892994 TI - How actively should dystocia be treated? PMID- 2892995 TI - Pelagic paralysis. AB - Three conditions that may occur after consumption of seafood--puffer fish poisoning, ciguatera, and paralytic shellfish poisoning--are caused by a group of poisons that block voltage-gated sodium channels in myelinated and non-myelinated nerves. The conditions cannot be distinguished clinically and so constitute an entity for which the name pelagic paralysis is proposed. Variations in the clinical features can be accounted for by large differences in the amount of toxin present in the seafood. PMID- 2892997 TI - Cholesterol embolisation: a lethal complication of vascular catheterisation. AB - Cholesterol embolisation after vascular catheterisation occurred in 5 patients. It tended to be associated with difficult manipulation of the catheter within a severely diseased aorta, and a common feature is leg pain with livedo reticularis despite palpable pulses. Confusion, renal failure, and death ultimately ensue. PMID- 2892996 TI - Skin and soft-tissue infections. PMID- 2892998 TI - What criteria should guide decision makers for incompetent patients? PMID- 2892999 TI - Typhoid vaccines. PMID- 2893000 TI - Intravenous captopril in acute heart failure. PMID- 2893001 TI - Percutaneous dynamic removal of atheroma. PMID- 2893002 TI - Chromosomes and screening for neuroblastoma. PMID- 2893003 TI - Caudate lesions as surgical treatment in Parkinson's disease. PMID- 2893004 TI - Difficult intubation. PMID- 2893005 TI - Cytomegalovirus pneumonitis. PMID- 2893006 TI - Clinical comparison of Campylobacter jejuni and C coli diarrhoea. PMID- 2893007 TI - Osteoporosis. PMID- 2893008 TI - T-lymphocyte alveolitis, tropical spastic paresis, and Sjogren syndrome. PMID- 2893009 TI - Listeriosis and food-borne transmission. PMID- 2893010 TI - Mechanical ventilation for the newborn. PMID- 2893011 TI - Aspirin and stroke prevention. PMID- 2893012 TI - Prolonged respiratory depression caused by sublingual buprenorphine. PMID- 2893013 TI - The ten-day rule. PMID- 2893014 TI - Perspectives on radiocaesium in the general public. PMID- 2893015 TI - Scratch test in clinical examination of liver. PMID- 2893016 TI - Cycads and sago. PMID- 2893017 TI - Safety helmet law in Italy. PMID- 2893018 TI - Interpretation of fetal breathing movements in oligohydramnios due to membrane rupture. PMID- 2893019 TI - Fetal viability in multiple pregnancy. PMID- 2893020 TI - Limitations of GIFT. PMID- 2893021 TI - Needle size and risk of miscarriage after amniocentesis. PMID- 2893022 TI - Mazindol in Duchenne muscular dystrophy. PMID- 2893023 TI - Clostridia and neutropenic enterocolitis. PMID- 2893024 TI - Concurrent hepatitis B and disseminated gonococcal infection associated with defective opsonisation. PMID- 2893025 TI - GOBI and infant mortality. PMID- 2893026 TI - Termination of pregnancy limit: 28, 24, or 18 weeks. PMID- 2893027 TI - Drug abuse strategies. PMID- 2893028 TI - Epilepsy and headache. PMID- 2893029 TI - Syringe pump safety lock. PMID- 2893030 TI - Isolation of HIV-2 in Central Africa from AIDS patient and her symptom-free partner. PMID- 2893031 TI - HIV-2 antibodies in African with spastic paraplegia. PMID- 2893033 TI - Incidence of IgA nephropathy in UK. PMID- 2893032 TI - Risk of virus transmission by jet injection. PMID- 2893034 TI - Relapse after autografting with peripheral blood stem cells. PMID- 2893035 TI - Exceptionally low cancer incidence in doctors. PMID- 2893036 TI - Propofol and malignant hyperpyrexia. PMID- 2893037 TI - Thrombolysis with tissue plasminogen activator in acute myocardial infarction: no additional benefit from immediate percutaneous coronary angioplasty. AB - A randomised trial of 367 patients with acute myocardial infarction was performed to determine whether an invasive strategy combining thrombolysis with recombinant tissue-type plasminogen activator (rTPA), heparin, and acetylsalicylic acid, and immediate percutaneous transluminal coronary angioplasty (PTCA) would be superior to a noninvasive strategy with the same medical treatment but without immediate angiography and PTCA. Intravenous infusion of 100 mg rTPA was started within 5 h after onset of symptoms (median 156 min). Angiography was performed 6-165 min later in 180 out of 183 patients allocated to the invasive strategy; 184 patients were allocated to the non-invasive strategy. Immediate PTCA reduced the percentage stenosis of the infarct-related segment, but this was offset by a high rate of transient (16%) and sustained (7%) reocclusion during the procedure and recurrent ischaemia during the first 24 h (17%). The clinical course was more favourable after non-invasive therapy, with a lower incidence of recurrent ischaemia within 24 h (3%), bleeding complications, hypotension, and ventricular fibrillation. Mortality at 14 days was lower in patients allocated to non invasive treatment (3%) than in the group allocated to invasive treatment (7%). No difference between the treatment groups was observed in infarct size estimated from myocardial release of alpha-hydroxybutyrate dehydrogenase or in left ventricular ejection fraction after 10-22 days. Since immediate PTCA does not provide additional benefit there seems to be no need for immediate angiography and PTCA in patients with acute myocardial infarction treated with rTPA. PMID- 2893038 TI - Coronary thrombolysis and myocardial salvage by tissue plasminogen activator given up to 4 hours after onset of myocardial infarction. National Heart Foundation of Australia Coronary Thrombolysis Group. AB - 144 patients presenting within 4 h of onset of myocardial infarction were randomised to receive either 100 mg of single-strand recombinant tissue plasminogen activator (rTPA) in 3 h (n = 73) or placebo infused at the same rate (n = 71). All patients were given heparin 5000 units before the infusion and heparin was continued, initially at 1000 units per hour, after the infusion. Minor bleeding was more frequent in the rTPA recipients, and during subsequent anticoagulant therapy there were three clinically significant bleeding episodes in this group. Patency of the infarct-related coronary artery was determined by coronary angiography about one week post-infarction, 125 angiograms being assessable. The infarct-related artery was patent in 70% of patients who received rTPA and in 41% of those who did not (p = 0.0015). In the 103 patients who had assessable contrast ventriculograms, the global ejection fractions were 57.7% and 51.7%, respectively (p = 0.04). The difference in ventricular function was largest in patients with anterior infarction (52.7% versus 40.0%, p = 0.02). The magnitude of these changes suggests an improvement in ejection fraction of 12% overall and about 30% in patients with anterior infarction. PMID- 2893039 TI - Stimulation of endothelial cell growth by sera from diabetic patients with retinopathy. AB - An in-vitro proliferation assay has shown that sera from patients with diabetic retinopathy, particularly those with the proliferative form, are two to four times more effective than sera from non-diabetics at stimulating 3H-thymidine incorporation into both human umbilical vein and human omental microvascular endothelial cells, but not at stimulating incorporation into human dermal fibroblasts or 3T3 cells. The factor(s) is heat stable and of molecular weight greater than 15,000, and its presence is unrelated to metabolic control. It is not present in patients with other forms of diabetic vascular disease, which suggests that it is not related to carbohydrate or lipid metabolism. These results provide evidence against the hypothesis that metabolic disturbances are central to the development of diabetic microvascular disease, and raise possibilities of novel forms of therapeutic intervention. PMID- 2893040 TI - A study of the genesis of colic. AB - To investigate local events in the gut as well as the location and duration of discomfort associated with colic, mild phasic pain was induced by balloon distension and bolus injection of normal saline at various sites in the gut of 1 normal volunteer and 12 patients with gut disorders. Intraluminal pressures were recorded. Pain was experienced only when a rise in baseline pressure occurred in a segment of gut at least 6 cm and up to 32 cm long. Painful segmental pressure rises were often low compared with non-painful localised pressure rises. Induced phasic pain had all the characteristics of colic, usually lasted less than a minute in both small and large intestine, and while frequently beginning paracentrally, tended to spread across the midline with increasing severity. PMID- 2893042 TI - HTLV-1 comes of age. PMID- 2893041 TI - Custom tube drains. PMID- 2893043 TI - Treatment of brain abscess. PMID- 2893045 TI - Fractures of the nose. PMID- 2893044 TI - Bile acid sequestrants and hyperlipidaemia. PMID- 2893046 TI - Obstetric anaesthesia on report. PMID- 2893047 TI - Unsuitability of World Health Organisation guidelines for fluoride concentrations in drinking water in Senegal. AB - A survey was done of the prevalence of dental fluorosis among children aged 7-16 years and the occurrence of skeletal fluorosis among adults aged 40-60 years living in regions in Senegal where fluoride concentrations in the drinking water ranged from less than 0.1 to 7.4 mg/l. In the area where the fluoride concentration in the drinking water was 1.1 mg/l milder forms of dental fluorosis were found, the prevalence being 68.5%. In areas where fluoride concentrations exceeded 4 mg/l the prevalence of dental fluorosis reached 100%. Kyphosis was very prevalent among a community whose drinking water contained 7.4 mg/l fluoride. Radiographs of the vertebral column, hand, and wrist of 3 adults with kyphosis confirmed the diagnosis of skeletal fluorosis. High sweat loss and a high intake of water because of the hot weather may account for the finding. The present World Health Organisation guideline for the upper limit of fluoride concentration in drinking water may be unsuitable for countries with a hot, dry climate. PMID- 2893048 TI - Surgical prophylaxis--the emerging picture. PMID- 2893049 TI - Rehabilitation status: a measure of medicosocial dysfunction. AB - The Edinburgh Rehabilitation Status Scale (ERSS) measures four dimensions in which changes may occur in the course of a disabling illness or during rehabilitation: independence; activity; social integration; and effects of symptoms on lifestyle. It provides a profile of measures, the scores of which can be summated to indicate the overall level of performance of individuals or groups. Studies of its inter-observer reliability and of its application in various disability groups indicate that the ERSS reliably defines the characteristics of individual patients and of groups. The scale can be used conveniently by professional staff working independently or by a multiprofessional rehabilitation team to assess status and changes in patients. It can also be used for measurement of the effectiveness of services and for purposes of research, teaching, and administration. PMID- 2893050 TI - Thrombolysis at home. PMID- 2893052 TI - Blood pressures, hearts, and U-shaped curves. PMID- 2893051 TI - Percutaneous angioplasty in renovascular hypertension. PMID- 2893053 TI - Abnormal retinal function associated with long-term etretinate? PMID- 2893054 TI - Isotretinoin dose and teratogenicity. PMID- 2893055 TI - Megadose vitamin A and teratogenicity. PMID- 2893056 TI - Renal autotransplantation for severe sickle cell haematuria. PMID- 2893057 TI - Failure of dapsone/pyrimethamine plus chloroquine against falciparum malaria in Papua New Guinea. PMID- 2893058 TI - Cervical dysplasia and HIV infection. PMID- 2893059 TI - HIV testing on all pregnant women. PMID- 2893060 TI - Combination therapy after retroviral inoculation. PMID- 2893061 TI - Classifying benign breast changes. PMID- 2893062 TI - Neutrophil accumulation in chronic obstructive lung disease. PMID- 2893064 TI - Benzodiazepines in anxiety. PMID- 2893063 TI - IgG1 subclass deficiency in patients with chronic fatigue syndrome. PMID- 2893065 TI - Vitamin B12 and seaweed. PMID- 2893066 TI - Acute leukaemia during pregnancy. PMID- 2893067 TI - Intravascular coagulation and Mycoplasma pneumoniae infection. PMID- 2893068 TI - Early diagnosis of hydatidosis by ultrasonography. PMID- 2893069 TI - The full potential of ultrasound. PMID- 2893070 TI - Need for radiographs in the acutely injured ankle. PMID- 2893071 TI - Charges for preventive services. PMID- 2893072 TI - Long-term antibiotic treatment in reactive arthritis. PMID- 2893073 TI - Rapidly progressive aortic stenosis associated with hyperparathyroidism in renal failure. PMID- 2893074 TI - Airflow limitation--reversible or irreversible? PMID- 2893075 TI - Alkaline phosphatase levels in renal transplant recipients receiving cyclosporin or azathioprine/steroids. PMID- 2893076 TI - Bioactivity and immunoreactivity of tumour necrosis factor in cancer patients. PMID- 2893077 TI - Adhesion molecules, immunosurveillance, and B-cell malignancies. PMID- 2893078 TI - Recombinant alpha 2-interferon treatment in children with chronic hepatitis B. PMID- 2893079 TI - Diltiazem for tardive dyskinesia. PMID- 2893080 TI - Treatment of patients with symptomless left ventricular dysfunction after myocardial infarction. AB - In a randomised, double-blind trial 60 patients with left ventricular dysfunction (ejection fraction less than 45%) but without clinical evidence of heart failure 1 week after Q wave myocardial infarction were given captopril 25 mg thrice a day, frusemide 40 mg daily, or placebo. Left ventricular volumes were measured at baseline and at 1, 3, 6, 9, and 12 months with cross-sectional echocardiography and Simpson's rule analysis of standardised apical views. The captopril group showed no significant change in left ventricular end-diastolic volume index but left ventricular end-systolic volume index was significantly reduced and stroke volume index and ejection fraction were significantly increased from 1 month on. In contrast, the frusemide and placebo groups showed significant increases in ventricular volumes, with stroke volume index unchanged and ejection fraction slightly reduced. The changes in the captopril group were significantly different from those in the other groups. PMID- 2893081 TI - Human immunodeficiency virus detected in bowel epithelium from patients with gastrointestinal symptoms. AB - Infectious human immunodeficiency virus (HIV) was recovered from two out of four bowel biopsy specimens from acquired immunodeficiency syndrome (AIDS) patients with chronic diarrhoea of unknown aetiology. In-situ hybridisation of biopsy specimens from rectum and duodenum of other AIDS patients with gastrointestinal complaints showed the presence of HIV-infected cells in both the base of the bowel crypts and the lamina propria. The type(s) of epithelial cell(s) infected could not be determined definitively. However, the association of in-situ labelling of HIV RNA in argentaffin staining cells strongly suggests that enterochromaffin cells derived from neural crest tissue are among the target cells. This evidence that HIV can directly infect the bowel raises the possibility that the virus causes some of the gastrointestinal disorders of AIDS patients. PMID- 2893082 TI - Prenatal testing for Duchenne and Becker muscular dystrophy. AB - DNA studies were undertaken following 53 requests from pregnant women at risk for Duchenne and Becker muscular dystrophy, including 32 in whom there was only 1 affected individual in the family (sporadic cases). The DNA restriction fragment length polymorphisms were informative in 51 of the 53 cases. In 10 of 25 pregnancies with male fetuses the risk to the fetus was reduced to 5% or less. Referral of possible carriers before onset of pregnancy is strongly advisable on both medical and economic grounds. The banking of DNA from affected individuals for future use in the estimation of risks to their relatives should be encouraged. PMID- 2893083 TI - Prevalence of Mycoplasma genitalium determined by DNA probe in men with urethritis. AB - The prevalence of urethral infection with Mycoplasma genitalium was determined by use of a DNA probe in 203 men attending a sexually transmitted disease clinic. M genitalium was detected in 3 (14%) of 21 with acute gonococcal urethritis; 3 (10%) of 30 with acute chlamydia-positive non-gonococcal urethritis (NGU); 4 (13%) of 31 with acute chlamydia-negative NGU; 10 (27%) of 37 with persistent or recurrent NGU; and 10 (12%) of 84 with no urethritis. The organism was more prevalent in homosexual (11 [30%] of 37) than in heterosexual men (19 [11%] of 166; p = 0.009). These data do not support an important aetiological role for M genitalium in acute urethritis, but suggest that it may account for some cases of NGU that become persistent or recurrent. The higher prevalence of urethral infection in homosexual men suggests that M genitalium may reside in the gastrointestinal tract. PMID- 2893084 TI - Multimodal approach to screening for ovarian cancer. AB - 1010 postmenopausal women were recruited for an ovarian cancer screening programme incorporating serum CA-125 measurement and vaginal examination as initial tests and real-time ultrasonography as a secondary procedure in selected cases. The normal range for serum CA-125 in postmenopausal women was established. The specificity for ovarian cancer of serum CA-125 measurement and vaginal examination were 97.0% and 97.3%, respectively. The combinations of serum CA-125 measurement with ultrasound and vaginal examination with ultrasound achieved specificities of 99.8% and 99.0%, respectively. 100% specificity was achieved by serum CA-125 measurement with vaginal examination and by the combination of all three tests. The findings indicate that no individual screening test has acceptable specificity for ovarian cancer in postmenopausal women. However, the combination of CA-125 measurement with ultrasound did achieve acceptable specificity and offers the most hope of a specific and sensitive method for early detection. PMID- 2893085 TI - Investigation of leukaemia clusters by use of a Geographical Analysis Machine. AB - A new spatial analysis device called a Geographical Analysis Machine detects deviations from the Poisson distribution of rare events. Application to childhood leukaemia data from the north of England identified five clusters, only one of which had been noted by previous methods. PMID- 2893086 TI - Management of venous thromboembolism. PMID- 2893088 TI - Bepridil. PMID- 2893087 TI - Splints don't stop colds--surprising! PMID- 2893090 TI - When editors agree. PMID- 2893089 TI - A job for life. PMID- 2893091 TI - Active-life expectancy and terminal dependency: trends in long-term geriatric care over 33 years. AB - To determine whether medical advances will result in an increasing number of dependent elderly people, or whether postponement of disability in a finite lifespan will lead to a decrease in terminal dependency, an analysis was made of 24,117 admissions to a geriatric unit from 1954 to 1986. During this period, the average age on admission for long-term care rose by 0.24 years per year for women and by 0.09 years per year for men. The median length of stay also increased, more for women than for men, as did the proportion of the total lifespan spent in long-term care. Active-life expectancy became longer and terminal dependency was postponed, but the duration of terminal dependency increased. Active-life expectancy increased more rapidly in women than in men, as did the length of terminal dependency. As life expectancy continues to increase, high priority will have to be given to reduction of disability and dependency in advanced old age. PMID- 2893093 TI - Antibiotic therapy--a resume. PMID- 2893092 TI - Identification of children with cerebral palsy unable to maintain a normal nutritional state. AB - 7 children aged 2-16 with severe cerebral palsy and growth failure were compared with children of the same weight in respect of their eating efficiency. Children with cerebral palsy took 2-12 times longer to chew and swallow a standard amount of pureed food and 1-15 times longer for solid food than did their weight controls. A behaviour score of feeding characteristics was higher in children with cerebral palsy than in controls. Even long meal times do not compensate for the severity of these childrens' feeding impairment. The measurements of feeding efficiency provides the basis for early identification of children who cannot be adequately nourished without ancillary feeding by nasogastric tube or by enterostomy. PMID- 2893094 TI - Surgical emergencies after prenatal treatment for intra-abdominal abnormality. AB - Emergency surgery was required in three babies who had been treated prenatally after ultrasonic detection of gastrointestinal abnormality. There are at present no indications for prenatal intervention in such babies. PMID- 2893095 TI - Hyperalgesia in premature infants. PMID- 2893096 TI - Ploidy as prognostic determinant in lung cancer. PMID- 2893097 TI - Updated Kiel classification for lymphomas. PMID- 2893098 TI - Renal transplantation and the skin. PMID- 2893099 TI - Acid-fast bacilli in Crohn's disease. PMID- 2893100 TI - Impact of surgery on survival in locally advanced breast cancer. PMID- 2893102 TI - Human parvovirus infection and seronegative-like arthritis in adults. PMID- 2893101 TI - Piezoelectric lithotripsy. PMID- 2893103 TI - Poxviruses isolated from epidemic erythromelalgia in China. PMID- 2893104 TI - Propofol and electroconvulsive therapy. PMID- 2893105 TI - Reactivities of antibodies to HIV and SIV in human sera in Kenya, Gabon, and Ghana. PMID- 2893106 TI - False positive anti-HIV tests on blood donations. PMID- 2893107 TI - Reproducibility of HIV antigen test. PMID- 2893108 TI - Extraoral origin of Eikenella corrodens infection. PMID- 2893109 TI - Probable toxicity of surface-active agent in commercial herbicide containing glyphosate. PMID- 2893110 TI - False positivity with third-generation (monoclonal) assay for hepatitis B surface antigen. PMID- 2893111 TI - Is yawning a brainstem phenomenon? PMID- 2893112 TI - Origin of spiral organisms in human gastric antrum. PMID- 2893113 TI - Too many H2 antagonists? PMID- 2893115 TI - Virulence of Campylobacter strains and degree of gastritis. PMID- 2893114 TI - Epidemic jejunitis. PMID- 2893116 TI - Peptic ulcers in childhood. PMID- 2893117 TI - Sleeping with bed-head raised in patients with severe peptic oesophagitis. PMID- 2893118 TI - Criteria for severe aplastic anaemia. PMID- 2893119 TI - Efficacy of bromine biocide in cooling-water systems. PMID- 2893120 TI - Role of paediatrician in child sexual abuse cases. PMID- 2893121 TI - Amoxycillin/clavulanate resistant Escherichia coli. PMID- 2893122 TI - Hydrogen sulphide poisoning in factory worker. PMID- 2893123 TI - Mycobacterial culture: how long? PMID- 2893124 TI - Fetal breathing is not a predictor of pulmonary hypoplasia in pregnancies complicated by oligohydramnios. PMID- 2893125 TI - Potential pathogenicity of Leuconostoc. PMID- 2893126 TI - Vancomycin-resistant Leuconostoc. PMID- 2893127 TI - Genetic inheritance and plasma fibrinogen. PMID- 2893128 TI - Smoking and plasma fibrinogen. PMID- 2893129 TI - Vivax relapse after falciparum malaria. PMID- 2893130 TI - Hypercalcaemia of malignancy. PMID- 2893131 TI - Childhood leukaemia incidence around nuclear installations. PMID- 2893132 TI - Radiation risks and ICRP inaction. PMID- 2893133 TI - Cupping brings back memories. PMID- 2893134 TI - The future of the NHS. PMID- 2893135 TI - Standard of proof in evidence of child abuse. PMID- 2893136 TI - Percutaneous oxygen delivery to the preterm infant. AB - The feasibility of delivering therapeutically useful amounts of oxygen percutaneously was investigated in 13 preterm infants. Their gestation ranged from 25 to 31 weeks and all were being ventilated for severe respiratory distress. Raising the ambient oxygen concentration resulted in an increase in arterial oxygen tension of 4.5 to 13.8 mm Hg (mean 8.9 mm Hg) as a result of percutaneous oxygen absorption. The change was greatest in the least mature infants and in those with the weakest epidermal barrier. Transdermal oxygen therapy can usefully supplement oxygen delivery to very premature infants with poor pulmonary gas exchange. PMID- 2893138 TI - Suppression of hepatitis B antibody synthesis by factor made by T cells from chronic hepatitis B carriers. AB - Mononuclear cells taken from subjects who had been immunised with hepatitis B vaccine could be stimulated by pokeweed mitogen plus hepatitis B surface antigen to synthesise antibody to hepatitis B surface antigen in vitro. Such synthesis was suppressed by supernatants of cultures of T cells from hepatitis B surface antigen carriers. The suppressor activity of this soluble factor in the supernatants was specific for anti-HBs since it did not affect production of polyclonal immunoglobulins or specific antibody to tetanus toxoid and since its effect was completely absorbed by a hepatitis B surface antigen column. The suppressor factor was made by T-cell cultures but not by non-T-cell cultures. T cells for 13 out of 15 carriers produced this factor. PMID- 2893137 TI - Growth without growth hormone: the "invisible" GH syndrome. AB - Growth hormone (GH) deficiency, diagnosed by radioimmunoassay (RIA) measurements of GH in blood after provocation or in continuous 24 h samples of venous blood, is usually associated with growth failure. 4 non-obese boys have been identified who had normal linear growth despite apparent GH deficiency by standard RIA. All 4 patients had normal GH concentrations as measured with an IM-9 cell radio receptor assay (RRA). The RRA/RIA ratio of the 4 patients significantly exceeded that of controls. Thus, these patients secrete a molecule with normal GH receptor binding and bioactivity which is "invisible" to the standard GH RIA. This variant GH is possibly expressed from the human GH-V gene or a mutant allele. PMID- 2893139 TI - Clinical and metabolic features of ethanol-methanol poisoning in chronic alcoholics. AB - The kinetics of methanol were examined in 84 chronic alcoholics admitted after drinking a cleansing solution containing 90% ethanol and 5% methanol. On admission, the average blood methanol concentration was 20 mmol/l (64 mg/dl) and blood ethanol concentration was 39 mmol/l (179 mg/dl). Although these patients were not treated with ethanol, and methanol concentrations remained high as blood ethanol concentrations fell to zero, no acidosis or other signs of classic methanol poisoning developed. The rate of metabolism of methanol was correlated to the initial ethanol concentration. To avoid unnecessary invasive therapy, treatment of methanol poisoning should be based on the case history, clinical signs, and laboratory features-not solely on blood methanol concentrations. PMID- 2893140 TI - Genomic imprinting and carcinogenesis. AB - Genomic imprinting might play an important part in the development of several tumours. It is suggested that in Wilms' tumorigenesis, imprinting normally renders inactive a transforming gene on the maternally derived chromosome 11, leaving intact the paternally inherited chromosome 11 and the Wilms' transforming gene that it carries. A similar mechanism might account for the inheritance patterns of other tumours. PMID- 2893141 TI - Primary prevention of ischaemic heart disease with lipid-lowering drugs. PMID- 2893143 TI - Which type of colitis? PMID- 2893142 TI - Combating undernutrition in the Third World. PMID- 2893144 TI - Sleep and scoliosis. PMID- 2893145 TI - Painful bladder diseases: interstitial or abacterial cystitis? PMID- 2893146 TI - Preventing burns and scalds. PMID- 2893147 TI - Cholecystectomy: the dissatisfied customer. PMID- 2893148 TI - Hour of birth as a prognostic factor for perinatal death. AB - The analysis of the 220,540 births and 2152 perinatal deaths recorded in Switzerland between 1979 and 1981 showed a variation of perinatal mortality rates (PMR) according to the hour of birth. The PMR for babies born between 4 pm and 2 am was 12 per 1000, contrasting with a figure of 8.4 per 1000 for babies born between 2 am and 4 pm. This pattern, which was fairly constant throughout the week, was characterised by a slow and steady increase from the very early morning, reaching a maximum in the late evening. There was also an hour-to-hour variation in the proportion of babies born weighing less than 2500 g, with a maximum in the evening and a less pronounced peak in the morning: the mortality rates by birthweight were raised only in the evening. Since the availability of hospital staff and equipment also follows a circadian rhythm, the variation in PMR may be related to a circadian rhythm of quality of care or possibly to chronobiological or selection factors. PMID- 2893149 TI - Rapid reinfection by Giardia lamblia after treatment in a hyperendemic Third World community. AB - In a peri-urban shanty town in Lima, Peru, that was hyperendemic for Giardia lamblia, 44 children aged between 0.9 months and 10 years were effectively treated for Giardia lamblia with tinidazole. Stools were examined weekly in the 6 months after treatment to determine the rate of reinfection, and after reinfection stools continued to be examined. 98% of the children became reinfected with Giardia lamblia within 6 months, and after reinfection stool excretion of the parasite lasted a mean (SD) of 3.2 (3.3) months. The children's mean stool pH and their mean stool fat index was unaffected by Giardia lamblia reinfection. Treatment of all symptomless Giardia lamblia infections in a developing country hyperendemic for the disease is of questionable value because of rapid reinfection. PMID- 2893150 TI - The Santmyer swallow: a new and useful infant reflex. AB - A puff of air administered to the face of 102 subjects (from 33 week's gestation on the first day of life to age 42 years) elicited a reflex swallow identical to a normal primary peristaltic sequence in 88. Subjects who responded were younger than 24 months of age or severely disabled neurologically; those who did not respond were older than 11 months and free of neurological abnormality. Response was variable between 11 and 24 months. This swallow response appears to be a clinically useful but previously unrecognised infant reflex. PMID- 2893151 TI - The bilingual consultation. PMID- 2893152 TI - Blood pressure and erythropoietin. PMID- 2893153 TI - Misuse of oxytocin in labour. PMID- 2893154 TI - Risk gradient for malignant melanoma in individuals with dysplastic naevi. PMID- 2893155 TI - Carbon dioxide, brain damage, and cardiac surgery. PMID- 2893156 TI - Total body water and very-low-calorie diets. PMID- 2893158 TI - AIDS, sex, and genital ulceration. PMID- 2893157 TI - Immunising children infected with HIV. PMID- 2893159 TI - Interferon in myelofibrosis. PMID- 2893160 TI - NSAIDs, plasma half-lives, and adverse reactions. PMID- 2893161 TI - Why does placebo improve severe limb ischaemia? PMID- 2893162 TI - High levels of IgA antigliadin antibodies in patients who have IgA mesangial glomerulonephritis but not coeliac disease. PMID- 2893163 TI - Limitations of pulse oximetry. PMID- 2893164 TI - Haemolytic uraemic syndrome induced by Yersinia pseudotuberculosis. PMID- 2893165 TI - Falsely raised serum thyrotropin with modified immunoradiometric assay. PMID- 2893166 TI - Pancreatic abnormalities in type 2 diabetes mellitus. PMID- 2893168 TI - Health services in the occupied territories. PMID- 2893167 TI - Thalidomide for graft-versus-host disease after bone marrow transplantation. PMID- 2893171 TI - Abortion legislation. PMID- 2893169 TI - Mozambique: health and war. PMID- 2893170 TI - Courtroom science. PMID- 2893172 TI - Drug information for patients. PMID- 2893173 TI - Non-compliant or illiterate? PMID- 2893174 TI - Environmental toxins in Parkinson's disease. PMID- 2893175 TI - Neurotoxicity of manganese. PMID- 2893176 TI - Bromodialone poisoning. PMID- 2893177 TI - Alarming electrocardiographic changes caused by inadequately insulated temporary epicardial electrodes. PMID- 2893178 TI - Incidental neuroblastoma. PMID- 2893179 TI - Somatosensory evoked potentials and spinal decompression sickness. PMID- 2893180 TI - Spinal-cord degeneration in commercial divers. PMID- 2893181 TI - Plastic devices: new fields for old microbes. PMID- 2893182 TI - Desmopressin therapy in patients with acquired factor VIII inhibitors. PMID- 2893184 TI - Preprandial intranasal insulin. PMID- 2893183 TI - Prenatal exclusion of primary hyperoxaluria type 1. PMID- 2893185 TI - Fetus as ward of court? PMID- 2893186 TI - 'Opren' case arbitration. PMID- 2893187 TI - Effect of zidovudine on serum human immunodeficiency virus antigen levels in symptom-free subjects. AB - 18 men with longstanding human immunodeficiency virus (HIV) antigenaemia but no symptoms received zidovudine in low-dose regimens (250 mg 6-hourly, 500 mg 6 hourly, or 500 mg 12-hourly) with or without acyclovir. Serum HIV antigen rose in only 1 patient and declined significantly in 13 (to below cut-off values in 9). In the 1 subject from whom HIV antigen positive cerebrospinal fluid was obtained, the fluid was antigen negative after 12 weeks of treatment. Acyclovir treatment alone or in addition did not seem to influence serum antigen levels. In 7 untreated men serum antigen levels rose or remained stable during follow-up. CD4+ cell counts increased in 14/18 treated subjects and 1/7 untreated subjects. No disease progression was observed in either group. Regression of enlarged lymph nodes was seen in the zidovudine-treated subjects. Adverse reactions to the study drugs were infrequent and mild. Anaemia caused symptoms in 2, but serious leucopenia or neutropenia was not observed. PMID- 2893188 TI - Genetic differences between cystic fibrosis with and without meconium ileus. AB - 41 families with cystic fibrosis, (CF) were tested for restriction fragment length polymorphisms (RFLPs) detected by four DNA probes all of which are tightly linked to the CF gene. 17 of the families had an affected child with, and 24 had one without, meconium ileus. In all cases, CF segregates with these gene probes; however, those with and those without meconium ileus differed in haplotype for CF chromosomes with respect to pJ3.11, which suggests that because of multiallelism (different mutations of the same locus) some CF patients present with meconium ileus and others do not. PMID- 2893189 TI - A double-blind, randomised, placebo-controlled trial of fish oil in psoriasis. AB - 28 patients with stable chronic psoriasis completed a trial in which they were randomly allocated to receive either 10 fish-oil capsules ('MaxEPA') or 10 placebo capsules (olive oil) daily. Patients were specifically instructed not to change their normal diet. After 8 weeks' treatment there was a significant lessening of itching, erythema, and scaling in the active treatment group, with a trend towards an overall decrease in body surface area affected. No change occurred in the placebo group. PMID- 2893190 TI - Short versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Arbeitsgemeinschaft fur Padiatrische Nephrologie. AB - Two regimens of steroid treatment for the initial attack of idiopathic nephrotic syndrome in children were compared in a controlled multicentre study. Short course prednisone therapy consisted of 60 mg/m2 per 24 h until proteinuria had disappeared for 3 days, followed by 40 mg/m2 per 48 h until complete remission had occurred. The standard prednisone therapy was 60 mg/m2 per 24 h for 4 weeks, followed by 40 mg/m2 per 48 h for 4 weeks. 61 children with a first attack of idiopathic nephrotic syndrome were allocated at random to these groups. Urinary remission in the short-course group was achieved after 14 days of daily prednisone, and complete remission after an additional 16 days of alternate day prednisone. The cumulative rate of patients with sustained remissions after two years was significantly lower after the short course than after standard treatment (19% versus 41%, p = 0.001). The mean duration of remission in patients with a relapse was half as long after the short course (79 versus 169 days, p = 0.004). Complete initial remission of steroid responsive nephrotic syndrome can be obtained with half the standard prednisone dose, but the short course is followed by a higher rate of relapses, that require repeated prednisone administrations. In the long term, the standard regimen is preferable. PMID- 2893191 TI - Percutaneous removal of atheromatous plaques in peripheral arteries. AB - The peripheral Simpson "atherectomy" catheter was used to treat 21 patients with a total of 41 stenotic lesions (5 iliac, 35 superficial femoral, and 1 popliteal). 4 lesions were totally occluded and 16 (39%) were calcified. The mean (SD) degree of obstruction was reduced from 82.7 (14) to 21 (16)% (p less than 0.0001). Mean (SD) standardised walking distance increased from 79.9 (71.9) to 152.6 (89.7) m (p less than 0.0001); doppler index improved from 0.58 (SD 0.17) to 0.81 (0.16) (p less than 0.0001); performance on bicycle stress test rose from 276.3 (range 1-1100) to 584.8 (2-2250) watt-min; and index for 201Tl-scintigraphy of the lower leg increased from 0.68 (0.28) to 0.91 (0.36) (p less than 0.02). The improvement has been maintained for 6 months, the degree of stenosis on repeat angiography at 2-6 months (n = 14 lesions) being 20.7 (SD 13.7)% (unchanged from early post-treatment values). The only restenosis has been corrected by a repeat of the percutaneous procedure. PMID- 2893193 TI - Influenza spread: evidence from "down under". PMID- 2893192 TI - Profound reversible myocardial depression after anaphylaxis. AB - Profound myocardial depression developed in 2 patients after severe anaphylactic reactions following the induction of anaesthesia in 1 case and a bee-sting in the other. Neither patient had pre-existent cardiac disease. In both patients haemodynamic assessment, radionuclide ventriculography, and two-dimensional echocardiography confirmed the clinical impression of profound systolic myocardial dysfunction. Haemodynamic stability was attained by intra-aortic balloon counterpulsation, which was probably life-saving in both cases. Cardiac function improved rapidly although some contractile depression persisted for several days. At follow-up both patients had normal cardiac function with no evidence of underlying heart disease. PMID- 2893194 TI - Exercise and energy balance. PMID- 2893195 TI - Microsurgical lumbar discectomy--another surgical gimmick? PMID- 2893196 TI - To blot or not? PMID- 2893197 TI - Genetic markers in multiple endocrine neoplasia type 2. PMID- 2893198 TI - Risk estimation and screening in families of patients with medullary thyroid carcinoma. AB - Many gene carriers for multiple endocrine neoplasia type 2a (MEN 2a) do not manifest the disease, even into old age. Thus, a negative family history in a patient presenting with medullary thyroid carcinoma does not reliably exclude familial disease. Data are reported for the probability that the MEN 2a gene will either have manifested clinically or be detectable by stimulated calcitonin screening by a given age. These probabilities can be used to calculate individual risks and to guide screening. PMID- 2893199 TI - Team management of the elderly patient with hip fracture. AB - The management of 200 consecutive patients with hip fracture by a joint hospital and community team in Peterborough has shown that over half the patients could be discharged considerably earlier than is usual. The patients are cared for at home by the hospital-at-home nursing service and generally need much less nursing care than patients treated conventionally. In the first 10 months of the scheme 733 inpatient bed-days were saved and the average hospital stay of patients discharged home was reduced from 22.0 to 14.6 days. PMID- 2893201 TI - Vitamin/mineral supplementation and non-verbal intelligence. PMID- 2893200 TI - Subcutaneous apomorphine in parkinsonian on-off oscillations. AB - Subcutaneous apomorphine, a dopamine agonist, was given by continuous infusion during the day or by repeated injections to 19 patients with Parkinson's disease disabled by severe on-off fluctuations. All patients were also given domperidone. The 11 patients treated by infusion showed marked and sustained improvement, and their mean duration of daily off periods over a period of 15 months fell by 6.3 h; similar results were obtained in 8 patients with less severe disabilities who were given repeated apomorphine injections. The therapeutic response to apomorphine was similar to that seen with intravenous levodopa; in patients treated by infusion the mean daily levodopa dose was reduced by 209 mg. These results confirm that during off periods dopamine receptors remain responsive to stimulation and provide evidence of a new, effective, and well-tolerated treatment for the most disabling complication of long-term levodopa therapy. PMID- 2893202 TI - Aspirin, warfarin, and stroke prevention. PMID- 2893203 TI - Faint palatal rash and viral labyrinthitis. PMID- 2893204 TI - Low-dose aspirin in pregnancy. PMID- 2893205 TI - Retrovirus-like particles in monocytes of patients with breast cancer. PMID- 2893206 TI - Rapid alkalinisation for flavone acetic acid administration: a potentially hazardous procedure. PMID- 2893207 TI - Immune thrombocytopenia caused by flavone-8-acetic acid. PMID- 2893208 TI - Number of events in tumorigenesis. PMID- 2893210 TI - Change of HLA phenotype in postoperative erythroderma. PMID- 2893209 TI - Intranasal calcitonin and prevention of postmenopausal bone loss. PMID- 2893211 TI - Importing khat. PMID- 2893212 TI - Toxicity of herbicide containing glyphosate. PMID- 2893213 TI - Arsenic and cancers. PMID- 2893214 TI - Should the dose of hepatitis B vaccine be reduced in newborn babies? PMID- 2893215 TI - Pulse oximetry in children. PMID- 2893217 TI - Estimating maternal mortality in developing countries. PMID- 2893216 TI - Hyper-IgE/recurrent staphylococcal infection syndrome. PMID- 2893218 TI - Bacterial diarrhoea and treatment. PMID- 2893219 TI - A decade of Campylobacter pylori. PMID- 2893220 TI - Galactose residues in chronic inflammatory disease. PMID- 2893221 TI - Transdermal glyceryl trinitrate as predictor of outcome of lumbar sympathectomy. PMID- 2893222 TI - Autologous blood stem cell transplantation in acute myeloid leukaemia. PMID- 2893223 TI - Addition of desmopressin to recombinant human erythropoietin in treatment of haemostatic defect of uraemia. PMID- 2893224 TI - Analgesic effects of oral flecainide. PMID- 2893225 TI - HIV testing on all pregnant women. PMID- 2893226 TI - Resumption of HIV antigen production during continuous zidovudine treatment. PMID- 2893227 TI - Addicted mothers and preterm babies: a disastrous outcome. PMID- 2893228 TI - Dangers of methotrexate/etretinate combination therapy. PMID- 2893229 TI - Drug misuse strategies and AIDS prevention. PMID- 2893230 TI - Fetal spare parts. PMID- 2893231 TI - [Multiple endocrine neoplasias in 3 generations]. AB - Typical in MEA IIb is a combination of medullary carcinoma of the thyroid gland and a pheochromocytoma with neurocutaneous and skeletal anomalies and a hyperplasia of the sympathetic nervous system of the GI tract with megacolon. Two patients of a family with MEA II are described. The family history reveals 1) an autosomal inheritance with high penetrance, 2) a changing pattern of anomalies in different generations, 3) no marfanoid traits as typical in MEA IIb, 4) only males affected by megacolon. This may be an uncommon variation or an additional type: IIc. Further investigation is required. PMID- 2893232 TI - Contractile responses to adrenergic nerve stimulation are enhanced with removal of endothelium in rat caudal artery. AB - Removal of the endothelium from isolated perfused rat caudal arteries produced a two fold increase in the contractile response to transmural nerve stimulation. Pretreatment with 6-hydroxydopamine eliminated the contractile response to adrenergic nerve stimulation but failed to uncover any vasodilatory effect of electrical stimulation, either directly on smooth muscle or via non-adrenergic nerves. Endothelial removal also produced two and four fold enhancement of the contractile responses to the selective alpha 1- and alpha 2-adrenoceptor agonists methoxamine and B-HT 920. However, pKB values for prazosin and yohimbine versus both agonists indicate that both methoxamine and B-HT 920 are acting primarily at alpha 1-adrenoceptors in this tissue. These results provide evidence that endothelial factors released either at basal levels or by the stimulation of agonists play a significant physiological role in modifying the contractile responses of blood vessels. PMID- 2893234 TI - Inhibition of cardiac Na+, K+-ATPase activity by dynorphin-A and ethylketocyclazocine. AB - The effect of various opioids on Na+, K+ -ATPase partially purified from rat heart was examined. Dynorphin-A (1-13), dynorphin-A (1-17) and ethylketocyclazocine (EKC), which are k-type opiate agonists, markedly inhibited the enzyme activity in a dose-dependent manner; IC50 values were 12 microM, 21 microM and 0.38 mM, respectively. Morphine (mu-type agonist), methionine- and leucine-enkephalin (delta-type agonist) at the concentration of 1 mM did not affect the enzyme activity. The effect of dynorphin-A (1-13) and EKC was not antagonized by naloxone. Dynorphin-A (1-13) mainly decreased Vmax value without the change of Km value in the activation of Na+, K+-ATPase by ATP, Na+ and K+. Dynorphin-A(1-13) inhibited the partial reactions of Na+, K+-ATPase at the different degree of the potency; the inhibition of K+-stimulated phosphatase was greater than that of Na+-dependent phosphorylation. The present study suggests that dynorphin-A and EKC have an effect on cardiovascular system which is mediated by the inhibition of Na+, K+-ATPase in the heart. PMID- 2893233 TI - Endothelium-dependent contraction induced by nicotine in isolated canine basilar artery--possible involvement of a thromboxane A2 (TXA2) like substance. AB - The present experiments were undertaken to determine whether the response to nicotine in the isolated canine cerebral artery is endothelium-dependent. Changes in the tension of arterial strips were recorded isometrically. Removal of the endothelium was carried out by gentle rubbing, and confirmed by scanning electron microscopy. Rubbing procedure did not affect the contractile response of the strips to serotonin. Treatment of unrubbed strips with nicotine (10(-4)M) caused a transient contraction. This response was abolished by removal of endothelium and attenuated by hexamethonium (5 x 10(-6)M) and atropine (10(-6)M). The nicotine-induced contraction was attenuated also by aspirin (5 x 10(-5)M), a cyclooxygenase inhibitor, OKY-046 (5 x 10(-5)M), a thromboxane A2 (TXA2) synthetase inhibitor and ONO-3708 (5 x 10(-9)M), a TXA2 antagonist. These results indicate that the nicotine-induced contraction in canine cerebral artery is endothelium-dependent, and suggest that the endothelium-derived contracting factor (EDCF) in the nicotine-induced response is a TXA2-like substance. PMID- 2893235 TI - Facilitation of the release of noradrenaline and neuropeptide Y by the alpha 2 adrenoceptor blocking agents idazoxan and hydergine in the dog spleen. AB - The release of noradrenaline (NA) together with its possible cotransmitter neuropeptide Y (NPY) was investigated in the perfused dog spleen. The splenic nerve was stimulated electrically at high frequency with bursts, which evoked a simultaneous release of both substances. Infusion of the alpha 2-adrenergic blocking agents idazoxan or hydergine enhanced the amount of NA and NPY in the venous effluent. The present results demonstrate the concomitant release of a classical neurotransmitter and a neuropeptide, and suggest that at high frequency stimulation, regulation of their release operates very similarly. PMID- 2893236 TI - GABA involvement in naloxone induced reversal of respiratory paralysis produced by thiopental. AB - No agent is yet available to reverse respiratory paralysis produced by CNS depressants, such as general anesthetics. In this study naloxone reversed respiratory paralysis induced by thiopental in rats. 25 mg/kg, i.v. thiopental produced anesthesia without altering respiratory rate, increased GABA, decreased glutamate, and had no effect on aspartate or glycine levels compared to controls in rat cortex and brain stem. Pretreatment of rats with thiosemicarbazide for 30 minutes abolished the anesthetic action as well as the respiratory depressant action of thiopental. 50 mg/kg, i.v. thiopental produced respiratory arrest with further increase in GABA and decrease in glutamate again in cortex and brain stem without affecting any of the amino acids studied in four regions of rat brain. Naloxone (2.5 mg/kg, i.v.) reversed respiratory paralysis, glutamate and GABA levels to control values in brain stem and cortex with no changes in caudate or cerebellum. These data suggest naloxone reverses respiratory paralysis produced by thiopental and involves GABA in its action. PMID- 2893237 TI - Modulation of GABA-stimulated chloride influx into membrane vesicles from rat cerebral cortex by triazolobenzodiazepines. AB - The effects of triazolobenzodiazepines on GABA-stimulated 36Cl- uptake by membrane vesicles from rat cerebral cortex were examined. Triazolam and alprazolam showed a significant enhancement of GABA-stimulated 36Cl- uptake at 0.01-10 microM. On the other hand, adinazolam showed a small enhancement at 0.1-1 microM followed by a significant inhibition of GABA-stimulated 36Cl- uptake at 100 microM. The enhancement of GABA-stimulated 36Cl- uptake by 1 microM alprazolam was antagonized by Ro15-1788, a benzodiazepine antagonist, but the inhibition of this response by 30 microM adinazolam was not antagonized by Ro15 1788. These results indicate that triazolobenzodiazepines enhanced GABA stimulated 36Cl- uptake through benzodiazepine receptors. High concentrations of adinazolam inhibit GABA-stimulated 36Cl- uptake which may be due to the direct blockade of GABA-gated chloride channel. PMID- 2893238 TI - Pharmacological specificity of some psychotomimetic and antipsychotic agents for the sigma and PCP binding sites. AB - The pharmacological specificity of representative psychotomimetic agents such as phencyclidine (PCP) analogs, opiate benzomorphans and several antipsychotic agents was assessed for the sigma and PCP binding sites. In a series of binding experiments, in rat brain membranes, sigma and PCP binding sites were labeled with [3H]-1-[1-(3-hydroxyphenyl)cyclohexyl]piperidine [( 3H]PCP-3-OH), (+) [3H]-N allylnormetazocine [(+) [3H]SKF 10047] and (+) [3H]-3-[3-hydroxy-phenyl]-N-(1 propyl)piperidine [(+) [3H]-3-PPP]. PCP analogs inhibit potently high affinity [3H]PCP-3-OH binding and (+) [3H]SKF 10047 binding, moderately the low affinity binding component of [3H]PCP-3-OH and very weakly (+) [3H]-3-PPP binding. (+)SKF 10047 and cyclazocine are potent to moderate inhibitors of (+) [3H]SKF 10047, high affinity [3H]PCP-3-OH and (+) [3H]-3-PPP binding, but extremely weak inhibitors of low affinity [3H]PCP-3-OH binding. The antipsychotic agents display high affinity for (+) [3H]-3-PPP binding sites, moderate affinity for (+) [3H]SKF 10047 sites and have no effect on either the high or low affinity [3H]PCP-3-OH binding. The present data further support the existence of multiple sigma and PCP binding sites. PMID- 2893239 TI - [Pseudomembranous colitis after antibiotic therapy associated with the presence of Entamoeba histolytica histolytica. Apropos of 2 cases]. AB - The authors report on two cases of pseudomembranous colitis (P.M.C.) developed in two Senegalese women of 38 and 36 years, and discovered at the 4th and 5th day respectively of an antibiotherapy based on ampicillin. In these two observations, cysts of Entamoeba histolytica histolytica were found in both feces and biopsies. They recall the circumstances of the occurrence, diagnosis techniques and treatment. They underline the unfrequency of this disease in Africa south of Sahara and they discuss the correlation with amoebiasis colitis. One has to keep in mind the possibility of a P.M.C. during any antibiotherapy, and consequently to have a rectoscopy to perform. Such an exploration is enough to pose a diagnosis. In day to day practice it is not necessary to show clearly the specific germ Clostridium difficile or its entero-toxin. To stop any antibiotherapy is required and beneficial. Metronidazole or Vancomycin are the best drugs in this case. PMID- 2893240 TI - Flumazenil in benzodiazepine antagonism. Actions and clinical use in intoxications and anaesthesiology. AB - In anaesthesia and in the intensive care unit, benzodiazepines have proven safe and effective agents for the induction and maintenance of sedation for a variety of therapeutic goals. However, in these contexts, or in benzodiazepine overdose, it is often desirable to be able to terminate or interrupt sedation without waiting for the effect of the benzodiazepine to become dissipated by normal metabolism and excretion. Flumazenil, a 1,4-imidazobenzodiazepine, is a highly effective, specific benzodiazepine antagonist which is indicated for use when the effect of a benzodiazepine must be attenuated or terminated at short notice. It acts by displacing other benzodiazepines from the receptor site by competitive inhibition. The onset of effect after intravenous administration occurs within 1 to 3 minutes. The optimal dosage is determined for each patient by a dose titration procedure and lies in the range 0.2 to 1.0mg in anaesthesiology, and 0.1 to 2.0mg in intensive care use. Despite its short elimination half-life of around 1 hour, after general anaesthesia or conscious to moderate sedation for short procedures, a single dose of flumazenil is usually sufficient to attain and maintain the desired level of consciousness. After intoxication with high benzodiazepine doses, the duration of effect of a single dose of flumazenil is not expected to exceed 1 hour. In such cases, the period of wakefulness can be prolonged as necessary by repeated low intravenous doses of flumazenil or by infusion (0.1 mg/hour). Flumazenil is well tolerated both systemically and locally. The only adverse events seen with greater frequency after flumazenil compared with placebo were nausea and/or vomiting after general anaesthesia, although the incidence of actual vomiting was not significantly different between the 2 groups. Since these effects were virtually absent in studies of intensive care patients and after sedation for short procedures, and were not seen in tolerability studies in healthy volunteers receiving intravenous bolus doses of up to 100mg, there may be a link between these symptoms and the other agents used in general anaesthesia, some of which have well-known emetic properties. Thus, flumazenil provides a safe and effective means of attenuating or reversing the CNS-depressant effects of benzodiazepines whenever indicated, e.g. following benzodiazepine-induced general anaesthesia, conscious sedation, or after benzodiazepine overdose, either alone or in combination with other agents.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2893241 TI - Impaired glucose handling in active rheumatoid arthritis: relationship to peripheral insulin resistance. AB - Glucose metabolism was studied after an intravenous glucose loading in normal weighted, previously untreated patients (n = 14) with active rheumatoid arthritis (RA). The patients displayed an enhanced insulin response and impaired glucose handling compared with healthy controls (P less than .001). The insulin sensitivity, measured as the glucose utilization rate during steady state of euglycemia (M) was significantly decreased (P less than .01) among the patients compared to the controls (5.5 +/- 1.9 mg/kg BW/min [mean +/- SD] and 7.2 +/- 1.2, respectively). The corresponding values for the metabolic clearance rate (MCR) were 5.8 +/- 0.6 mL/kg BW/min and 8.2 +/- 0.4, respectively (P less than .01). In the patient group the k value correlated with the peripheral insulin sensitivity (P less than .01), which, in turn, was inversely related to the acute phase reaction (P less than .05). During 1 week of potent anti-inflammatory treatment with corticosteroids (prednisolone 20 mg daily) the k value improved P less than .001), the insulin sensitivity tended to improve and the insulin response increased (P less than .001) after an intravenous glucose loading. Five patients who had a remission of their disease on sulphasalazine as antirheumatic therapy were reexamined. A normalization of the inflammatory activity as well as the glucose handling and insulin sensitivity was achieved. The data obtained indicate that impaired glucose handling in active RA is related to insulin resistance. The linkage between inflammatory indices and glucose metabolism might reflect a special consequence of inflammation, but the influence of nonspecific disease manifestations, ie, malnutrition, inactivity, and myopenia, has to be considered. PMID- 2893242 TI - Proliferating cell nuclear antigen: cyclin. PMID- 2893243 TI - E-rosette receptor in human lymphocytes. PMID- 2893245 TI - DNA and protein heterogeneity in serial isolates of human immunodeficiency virus (HIV-1): indication of change in vivo. AB - Structural heterogeneity in human immunodeficiency virus (HIV-1) isolates from different sources has been reported. In order to investigate if the virus exhibits heterogeneity in vivo, HIV-1 was isolated over a 3 year period (1983 1985) from a blood donor who progressed from the asymptomatic carrier state to frank AIDS. The HIV-1 specific proteins were characterized and compared by metabolic labelling and immunoprecipitation of infected cells and by Western blot analysis of gradient purified isolates. The data indicate polymorphism in the apparent size of gag gene-encoded p55 and env gene-encoded p41 proteins. The possibility of genomic variations was evaluated by studying the restriction enzyme polymorphism of integrated proviral DNA. Genetic diversity between 1983, 1984 and 1985 isolates was demonstrated by a change in the number and/or size of restriction fragments. In addition, genetic variation was also observed in HIV-1 isolated from the blood transfusion recipient of this donor. Subsequent analysis of the quantitative and qualitative titre of HIV-1 specific antibodies in the donor recipient sera demonstrated a concomitant change with the observed structural variation in the virus. These studies may be useful in elucidating virus or host-related critical events which lead to the onset of AIDS following infection with HIV-1. PMID- 2893246 TI - Choice of benzodiazepines. PMID- 2893247 TI - HTLV-I: the forgotten retrovirus. PMID- 2893244 TI - Deletion analysis of the promoter region of the Escherichia coli pepN gene, a gene subject in vivo to multiple global controls. AB - The pepN gene codes for aminopeptidase N whose expression is regulated at the transcriptional level by anaerobiosis and phosphate starvation. To define and characterize the functional region of the pepN promoter (pepNp), various promoter fragments were fused to the malPQ operon of Escherichia coli and transferred to the chromosome. The expression of the single copy operon fusion was measured by assaying the amylomaltase activity. Sequences upstream from the canonical promoter elements, located 110 to 60 bp preceding the transcription start site, are important for promoter functioning. This region plays a role in the expression of the two divergent promoters pepNp and pncBp. The regulation of pepNp under phosphate starvation was conserved in the various constructs in which pepNp is functional. However, no particular sequence specific for phosphate regulation was detected. In addition, the regulation of pncBp by Pi starvation was demonstrated. PMID- 2893248 TI - [Continuous subcutaneous opioid infusion in cancer pain therapy]. PMID- 2893249 TI - [Principles of pharmacotherapy in tumor-induced pain syndromes]. PMID- 2893250 TI - Korean hemorrhagic fever. PMID- 2893251 TI - Most drugs that reverse multidrug resistance also inhibit photoaffinity labeling of P-glycoprotein by a vinblastine analog. AB - Multidrug-resistant human KB carcinoma cells express a 170,000-dalton membrane glycoprotein (P-glycoprotein) that can be photoaffinity labeled with the vinblastine analog N-(p-azido-[3-125I]salicyl]-N'-(beta-aminoethyl)vindesine. Several agents that suppress the multidrug-resistant phenotype, including N solanesyl-N,N'-bis(3,4-dimethylbenzyl)ethylenediamine, cepharanthine, quinidine, and reserpine, were found to inhibit photolabeling of P-glycoprotein at doses comparable to those that reverse multidrug resistance. However, the phenothiazines chlorpromazine and trifluoperazine, which also effectively reverse multidrug resistance, were poor inhibitors of the photoaffinity labeling of P glycoprotein. Chloroquine, propranolol, or atropine, which only partially reversed the drug resistance, also did not inhibit photolabeling. Naphthalene sulfonamide calmodulin inhibitors, W7 and W5, as well as many other drugs that did not circumvent multidrug resistance, did not inhibit photolabeling. These studies suggest that most, but not all, agents that phenotypically suppress multidrug resistance also inhibit drug binding to a site on P-glycoprotein with which a photoaffinity analog of vinblastine interacts. PMID- 2893252 TI - Biosynthesis of the neurofilament heavy subunit in Xenopus oocytes microinjected with rat brain poly(A)+ RNA. AB - In order to study the expression of the major subunit of neurofilaments (NFs), rat brain poly(A)+ RNA was purified by three different procedures and was injected in Xenopus laevis oocytes. This system was able to translate efficiently the 200 kDa NF subunit as shown by a dot-blot immunoassay and by immunoprecipitation of labeled NF polypeptides. PMID- 2893254 TI - The yeast F1-ATPase beta subunit precursor contains functionally redundant mitochondrial protein import information. AB - The NH2 terminus of the yeast F1-ATPase beta subunit precursor directs the import of this protein into mitochondria. To define the functionally important components of this import signal, oligonucleotide-directed mutagenesis was used to introduce a series of deletion and missense mutations into the gene encoding the F1-beta subunit precursor. Among these mutations were three nonoverlapping deletions, two within the 19-amino-acid presequence (delta 5-12 and delta 16-19) and one within the mature protein (delta 28-34). Characterization of the mitochondrial import properties of various mutant F1-beta subunit proteins containing different combinations of these deletions showed that import was blocked only when all three deletions were combined. Mutant proteins containing all possible single and pairwise combinations of these deletions were found to retain the ability to direct mitochondrial import of the F1-beta subunit. These data suggest that the F1-beta subunit contains redundant import information at its NH2 terminus. In fact, we found that deletion of the entire F1-beta subunit presequence did not prevent import, indicating that a functional mitochondrial import signal is present near the NH2 terminus of the mature protein. Furthermore, by analyzing mitochondrial import of the various mutant proteins in [rho-] yeast, we obtained evidence that different segments of the F1-beta subunit import signal may act in an additive or cooperative manner to optimize the import properties of this protein. PMID- 2893256 TI - Banbury Center DNA Adducts Workshop. Workshop on DNA Adducts, Banbury Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY (U.S.A.), Sept. 30-Oct. 2, 1986. PMID- 2893253 TI - Regulation of mRNA polyadenylation-deadenylation. PMID- 2893255 TI - Simultaneous expression of two P-glycoprotein genes in drug-sensitive Chinese hamster ovary cells. AB - Overexpression of P-glycoprotein is characteristic of multidrug-resistant cells. We analyzed four P-glycoprotein transcripts that are simultaneously expressed in a drug-sensitive Chinese hamster ovary cell line. We concluded that these transcripts are encoded by two distinct members of a P-glycoprotein multigene family, each of which has two alternative polyadenylation sites. A comparison of the two hamster sequences with the single reported human and mouse P-glycoprotein cDNA sequences demonstrates that P-glycoprotein is a highly conserved protein, that the hamster multigene family is undergoing concerted evolution, and that differences between gene family members are maintained across species. These conserved differences suggest that there may be functional differences between P glycoprotein molecules. PMID- 2893257 TI - The polymorphic 11.1 locus of Plasmodium falciparum. AB - Clone pPF11.1 encodes a Plasmodium falciparum antigen expressed during the intraerythrocytic cycle and containing tandem repeats of a 9 amino acid unit. We report here an analysis of the genomic region specific for 11.1, which extends over 30 kb. It contains two blocks of repeats, spanning 13 kb and 9 kb. The restriction map suggests that the locus may result from a gene duplication. The 11.1 region is present in all P. falciparum strains examined so far. Southern analysis of 8 distinct isolates indicates that the locus is highly polymorphic. Thus the pPF11.1 repeats constitute a sensitive and discriminating probe to type P. falciparum strains. PMID- 2893258 TI - Catalytic classes of proteinases of Entamoeba histolytica. AB - Endopeptidase inhibitors were used to determine the catalytic classes of proteinases present in extracts of Entamoeba histolytica (strain HM 1:IMSS) axenically grown in vitro. Cysteine proteinases account for most of the proteolytic activity; one or more proteinases with different catalytic mechanisms are also present but could not be unambiguously assigned to a particular catalytic class. Proteinases in amebic lysates were resolved by polyacrylamide gel electrophoresis with sodium dodecyl sulfate. The detergent was exchanged with Triton X-100 and the proteolytic activity in the gels was demonstrated by overlaying it on another gel containing the substrate. Four lysis zones were observed corresponding to molecular weights of 66,000, 56,000, 40,000 and 27,000. The first cannot be classified yet, but the last three showed properties consistent with those of cysteine proteinases. Finally, a novel technique is described which uses purified human alpha-2-macroglobulin to trap, purify and characterize proteases from amebic lysates. The results obtained with this technique confirm those of the overlay technique, since both methods reveal four distinct proteinases in the two different amebic preparations examined. PMID- 2893259 TI - The clinical outcome of prospective screening for multiple endocrine neoplasia type 2a. An 18-year experience. AB - An important question facing physicians who care for families with multiple endocrine neoplasia type 2a is whether prospective screening to detect early abnormalities of the thyroid, parathyroid, or adrenal glands favorably influences the ultimate course of the disease. An 18-year study of a large family has allowed us to examine the effect of early treatment on the clinical course of the disease. Of 22 patients who underwent thyroidectomy for early C-cell abnormalities, 19 remained free of detectable medullary thyroid carcinoma according to all criteria, at a mean of 11 years after thyroidectomy. None of the 22 patients had evidence of parathyroid disease either at the time of surgery or after a mean follow-up of 10 years. Prospective screening for adrenal medullary abnormalities by means of measurement of 24-hour urinary epinephrine excretion and the ratio of urinary epinephrine to norepinephrine was predictive of pheochromocytoma in 10 of 11 patients (with a false negative result in one patient) but was not useful in diagnosing adrenal medullary hyperplasia. We conclude that regular, prospective screening and early treatment of the manifestations of multiple endocrine neoplasia can prevent metastasis of medullary thyroid carcinoma and the morbidity and mortality caused by pheochromocytoma. PMID- 2893260 TI - Predictive testing for Huntington's disease with use of a linked DNA marker. AB - The probability of carrying the gene for Huntington's disease can in many cases be estimated in the children of affected persons by identifying a specific DNA marker that is genetically linked to the gene. We studied 47 persons at 50 percent risk of inheriting Huntington's disease who requested a presymptomatic or prenatal genetic-linkage test between September 1986 and January 1988. The participants were given pre-test counseling and psychological and neurologic evaluations. Nineteen persons later voluntarily withdrew from the protocol, including one who would have been excluded anyway, and one person was from a family that was too small to allow testing. Three D4S10 restriction-fragment length polymorphisms produced by the HindIII, EcoRI, and Bg/I enzymes were used for all tests, and the probability that a subject was a Huntington's disease carrier was calculated. The accuracy of the test was compromised by a 4 percent recombination frequency between D4S10 and the Huntington's disease gene. Fifteen presymptomatic tests and one prenatal test were completed. Four yielded positive results, seven yielded negative results, and five were uninformative; seven persons are awaiting test results. All participants with positive tests experienced intermittent depression, but none required hospitalization, and no suicide threats were reported. Five participants received a diagnosis of Huntington's disease on the basis of the neurologic assessment. We conclude that some persons in the early stages of Huntington's disease may seek presymptomatic testing rather than neurologic evaluations. PMID- 2893261 TI - Opioid receptor activity in the dentate region of the rat hippocampus. AB - The electrophysiological actions of normorphine and dynorphin-A were compared in the dentate gyrus and CA1 regions of the rat hippocampus. In both regions, these opioids increased cell excitability and induced afterpotentials following electrical stimulation of synaptic afferents. Based upon apparent naloxone dissociation constants, we conclude that normorphine activated mu receptors in both regions. However, dynorphin-A appears to act via mu receptors in CA1, but kappa receptors in the dentate gyrus. PMID- 2893262 TI - Calmodulin content in rabbit reticulocyte and the influence of opioid peptides on calmodulin activity in its membrane. AB - Calmodulin (CaM) content in rabbit reticulocyte and the influence of opioid peptides on CaM activity in its membrane were studied by a highly sensitive assay of CaM activity based on the stimulation of Calcium-dependent phosphodiesterase activity. The CaM contents in reticulocytes were higher than those in normal erythrocytes, both in the cytosol fraction and in the membrane fraction. Among the opioid peptides, beta-endorphin (beta-EP) and dynorphin-A-(1-13) (dyn) had a significant inhibitory effect on CaM activity in reticulocyte membrane. The effect was not antagonized by naloxone or Mr. 2266, nor influenced by increase of Ca2+ concentration, but was reversed by the addition of exogenous CaM. This implies that the action of beta-EP and dyn on reticulocyte membranes probably involves an non-opioid mechanism, in which CaM may be an important key of linkage. PMID- 2893263 TI - Comparison of the opioid antagonist properties of a cyclic somatostatin analog in vitro and in vivo. PMID- 2893264 TI - H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2: a potent and selective antagonist opioid receptors. AB - H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) exhibited high affinity (IC50 = 2.80 nM) in displacing [3H]naloxone binding (nH = 0.89 +/- 0.1) and showed an exceptional selectivity for mu opioid receptors with an IC50(DPDPE)/IC50(naloxone) ratio of 4,840, while it displayed very low affinity for somatostatin receptors (IC50 = 22,700 nM) in rat brain binding assays. [3H]CTOP was recently custom synthesized (spec. act.: 84 Ci/mmol) and evaluated for its in vitro binding properties towards the mu opioid receptors in rat brain membrane preparations. Association and dissociation of [3H]CTOP binding to mu opioid receptors were rapid at 25 degrees C with a kinetic Kd value of 0.67 nM. Saturation experiments gave apparent Kd value of 1.11 nM and Bmax value of 136 +/ 13 fmol/mg prot at 25 degrees C. Specific [3H]CTOP binding was inhibited by a number of different opioid and opiate ligands. Among them, putative mu opioid receptor-specific ligands, such as naloxone, naltrexone and CTOP inhibited the binding with high affinity, while delta opioid receptor-specific compounds or non opioid drugs inhibited specific [3H]CTOP binding with low affinity or they were ineffective. PMID- 2893265 TI - Comparative effects of dynorphin A(1-9) pyrrolidine analogs on isolated tissues. AB - Three dynorphin A(1-9) pyrrolidine analogs were synthesized by substituting isoleucine at position 8 with alanine (Ala), D-alanine (D-ala), and D-leucine (D leu), and assayed for their effect on electrically induced twitches of the isolated guinea pig ileum and mouse vas deferens. All three dynorphin A(1-9) pyrrolidine analogs caused inhibition of the evoked twitches of the two preparations dose-dependently that was reversed by naloxone. However, the substitution by alanine or D-alanine resulted in a decrease in potency on guinea pig ileum when compared to dynorphin A(1-9) pyrrolidine and substitution by D leucine caused a considerable loss of potency in both mouse vas deferens and guinea pig ileum. Although these substitutions reduced overall potency, a change of potency ratio towards more delta selectivity resulted. PMID- 2893266 TI - 125I-DPDYN, monoiodo [D-Pro10]- dynorphin (1-11), is an effective and useful tool for the study of kappa opioid receptors. AB - Iodination of the kappa-selective peptide DPDYN, [D-Pro10]-dynorphin (1-11), has been performed. The non radioactive monoiodo derivative of DPDYN retains kappa selectivity (kappa/mu = 48 and kappa/delta = 140), despite a general but moderate decrease in affinity. Radioiodination of DPDYN leads to the monoiodinated peptide (S.A 700-800 Ci/mmol) which interacts specifically and reversibly with the kappa sites in guinea-pig cerebellum membranes with high affinity (KD = 0.12-0.18 nM). In guinea-pig brain (mu-delta-kappa) and rabbit cerebellum (kappa much less than mu), 125I-DPDYN discriminates between kappa- and other (mu, delta) binding sites. We have used this new labelled probe for the direct, precise and rapid (exposure time less than 100 hours) visualization of kappa-sites in guinea-pig and rabbit cerebellar slices using autoradiography. PMID- 2893267 TI - Bridge peptide is a cleavage product of pro-dynorphin processing in the rat anterior pituitary. AB - Bridge peptide, the sequence of amino acids which joins alpha-neo-endorphin and dynorphin A 1-17, was determined to exist as a free molecule in the rat anterior pituitary. Gel filtration chromatography revealed the presence of the free peptide as well as a high molecular weight intermediate of 8-9 kilodaltons. PMID- 2893268 TI - Assay and biochemical characterization of a dynorphin converting enzyme in human cerebrospinal fluid. AB - An endopeptidase hydrolyzing dynorphins A and B and alpha-neo-endorphin at the Arg6-Arg7 or Arg6-Lys7 bonds, was partially purified from human cerebrospinal fluid and further characterized by various biochemical techniques including HPLC gel permeation (UltroPac TSK G3000SW) and ion exchange (TSK DEAE-3SW) chromatography. A procedure for quantitative analysis of the enzyme in individual CSF samples is also described. The activity in lumbar CSF of women in late pregnancy was significantly lower than that in control samples. PMID- 2893269 TI - Immunohistochemical evidence for subpopulations of dynorphinergic neurons. AB - Biochemical studies have shown that the dynorphin precursor can generate at least seven opioid peptides. We report here a study of dynorphin products analyzed on adjacent semithin sections of rat brain, showing evidence for differential peptide localization among magnocellular neurons. In the oxytocinergic nucleus of the anterior commissure, staining was strong for dynorphin B but very weak for other prodynorphin markers; in the supraoptic nucleus, a discrete subset of dynorphin neurons were positive for leu-enkephalin. PMID- 2893270 TI - Immunohistochemical and subcellular studies of aminopeptidase M localization in rat brain: microvessels and synaptic membranes. AB - A predominantly microvascular localization of aminopeptidase M (APM) was established both by immunohistochemistry and biochemical studies of isolated microvessels. In addition a high relative specific activity of APM was evidenced in fractions enriched in synaptic membranes. PMID- 2893272 TI - Dopaminergic regulation of proenkephalin-A gene expression in the basal ganglia. AB - Dopaminergic denervation by 6-hydroxydopamine (6-OHDA) increased proenkephalin-A gene expression in the striatum as evidenced by increases in the levels of Met5 enkephalin (ME), precursor and preproenkephalin mRNA (PE-mRNA). This and other lines of evidence support the hypothesis that nigrostriatal dopamine input is inhibitory to striatal enkephalin neurons and that the removal of this inhibitory influence leads to an acceleration of ME biosynthesis. These findings suggest that the enkephalin system may be associated with the progression of adaptive changes subsequent to dopaminergic dysfunction in basal ganglia. PMID- 2893271 TI - beta-Endorphin modulates the inhibitory action of corticotropin-releasing factor on luteinizing hormone secretion. AB - The present study investigates the possible role of endogenous opioid peptides in mediating the inhibitory effect of corticotropin-releasing factor (CRF) on circulating luteinizing hormone (LH). The central injection of an antiserum against beta-endorphin (beta-END) reversed CRF-induced LH decrease in castrated male rats, while antisera raised against DYN-A or M-Enk were inactive. beta-END (6-31) (2 nmole, icv), a beta-END antagonist, and beta-funaltrexamine (4.8 nmole, icv), a mu 1 opiate receptor antagonist, also reversed the effect of CRF on LH. Either kappa (Mr 1456 and Mr 2266) (10 mg/kg, ip), or delta (ICI 154,129) (10 nmole, icv) opiate receptor antagonists did not significantly modify the inhibitory effect of CRF on circulating LH levels. These results suggest that central beta-END participates in the inhibitory action of CRF on LH secretion. PMID- 2893274 TI - Increased spinal cord dynorphin mRNA during peripheral inflammation. AB - Injection of a complete Freunds adjuvant-saline emulsion into the hindpaw of the rat induces a peripheral inflammatory process accompanied by pronounced increase (3 fold) in spinal cord dynorphin content. A marked increase (approximately 9 fold) in the mRNA coding for the preprodynorphin precursor accompanies the increase in peptide. The parallel elevations of the mRNA and peptide product suggest that an increased activity of dynorphin neurons occurs in spinal cord in response to altered afferent input due to the peripheral inflammatory process. PMID- 2893273 TI - Regulation of hypothalamic beta-endorphin and dynorphin release by corticotropin releasing factor (CRF). AB - Synthetic rat-human corticotropin releasing-factor (CRF), in doses between 10( 12) M and 10(-8) M, significantly stimulates the release of immunoreactive beta endorphin and dynorphin-A from rat hypothalamic slices superfused in vitro. With prolonged exposure to CRF, there is a reduction in the release of both opioids which can be reversed by the addition of naloxone. The latter result indicates the involvement of autoregulatory mechanisms in the control of opioid neuronal function. PMID- 2893275 TI - Differential effects of selective brain lesions on hypothalamic and pituitary ir dynorphin. AB - Selective radiofrequency and neurotoxic lesions of the serotonergic pathways caused in the rat a significant reduction of ir-dynorphin A and B in the hypothalamus but not at pituitary level. These data confirm that dynorphin related peptides are regulated independently in these areas. PMID- 2893276 TI - Release of i-r metenkephalin from rat amygdala slices in vitro. AB - Release of immuno-reactive metenkephalin has been demonstrated from slices of rat amygdala in vitro. This release was calcium dependent and the amount released was related to the concentration of potassium ions in the releasing stimulus. The effect of drugs such as clonidine, an alpha 2 adrenoceptor agonist, and idazoxan, an antagonist, on this release was measured. Neither drug had a significant effect on the amount of ir-metenkephalin released. Thus although release of noradrenaline can be affected by opioids it seems that release of endogenous opioids is not affected by drugs which interact with noradrenaline. PMID- 2893277 TI - Sensitivity of antinociceptive tests to opioid agonists and partial agonists. AB - There is considerable variation in the potency of opioids across different animal models of antinociceptive activity. In the less sensitive tests the partial agonist analgesics behave as antagonists. The activity of opioids in antinociceptive tests appears to be dependent on both the intensity of the noxious stimulus and the intrinsic activity of the drug. PMID- 2893278 TI - Modulators of pain in the spinal cord. AB - Intrathecal injection of subanalgesic doses of morphine (7.5 nmol) and dynorphin A-(1-13) (1.25 nmol) in combination resulted in a marked analgesic effect as assessed by tail flick latency in the rat. The analgesic effect of the composite of dynorphin/morphine was dose-dependent in serial dilutions and not accompanied by any signs of motor dysfunction. Synergism between dynorphin and morphine can also be demonstrated without motor dysfunction, when dynorphin is injected together intrathecally with a serial increasing dosages of morphine. Metenkephalin showed an analogous synergistic effect with dynorphin and also morphine in the spinal cord, although dynorphin (and also metenkephalin) antagonized morphine analgesia by the intraventricular route. The underlying mechanism of the interactions among different classes of opioid ligands at different levels of the central nervous system deserves further study. PMID- 2893279 TI - Effect of electrolytic and chemical ventromedial hypothalamic lesions on food intake, body weight, analgesia and the CNS opioid peptides in rats and mice. AB - The hyperphagia and obesity induced by ventromedial hypothalamic (VMH) electrolytic lesions in female rats were associated with a 70-94% decrease in the level of beta-endorphin (beta-E) in the hypothalamus and other regions of brain, but not in the pituitary. Dynorphin (Dyn) and methionine-enkephalin (ME) levels were also decreased. Rats with VMH lesions were less sensitive to the inhibitory effect of naloxone on their food-intake. Mice injected with gold thioglucose (GTG) also showed a decrease in the hypothalamic content of beta-E and Dyn and exhibited 30% less analgesia compared to control mice after cold swim stress. PMID- 2893280 TI - Intrathecal dynorphin A (1-13) and (3-13) reduce spinal cord blood flow by non opioid mechanisms. AB - Dynorphin A (Dyn A)-related peptides have been implicated in the pathophysiology of spinal cord injury in part because their intrathecal (i.t.) injection causes hindlimb paralysis. The effects of paralytic doses of i.t. Dyn A (1-13) and Dyn A (3-13) on spinal cord blood flow and cardiac output were examined in rats using radiolabeled microspheres. Both Dyn A (1-13) and Dyn A (3-13) significantly reduced blood flow in lumbosacral spinal cord without altering cardiac output. Pretreatment with naloxone failed to block these reductions in blood flow. Thus, the paralytic effects of Dyn A may result from non-opioid actions of Dyn A to reduce spinal cord perfusion. PMID- 2893281 TI - Endogenous opioids, opiate receptors and traumatic brain injury. AB - The present study examined the role of endogenous opioid peptides in the pathophysiological sequelae of fluid percussion head injury in the cat. Two hours following injury, tissue concentrations of dynorphin-like immunoreactive material (ir-Dyn) were significantly elevated in specific brain regions where injury, as evidenced by histological examination, was most severe. Changes in ir-Dyn but not beta-endorphin-like immunoreactive material (ir-End) were significantly correlated with a fall in regional cerebral blood flow (CBF) that occurred 2 h following injury. Administration of the opiate antagonist WIN44,441-3 (with enhanced activity at kappa-receptors) stereospecifically increased cerebral blood flow to the injured regions. PMID- 2893282 TI - Dynorphin A (1-13): in vivo opioid antagonist actions and non-opioid anticonvulsant effects in the rat flurothyl test. AB - Dynorphin A (1-13) acutely elevated the seizure threshold (ST) to the convulsant flurothyl, and this action was not blocked by naloxone. Increases in ST were also observed following i.c.v. injections of the non-opioid fragment dynorphin A (3 13). Pretreatment with dynorphin A (1-13), but not dynorphin A (3-13), non competitively blocked the anticonvulsant effect of the mu selective opioid DAGO. Furthermore, pretreatment with dynorphin A (1-13) antagonized the delta antagonist properties of naloxone or ICI 154,129 in this seizure model. Thus, in addition to its non-opioid anticonvulsant effects, dynorphin A (1-13) exhibits unique antagonist actions which appear to be specific for the active opioid fragment. PMID- 2893283 TI - Opioid receptors of bovine posterior pituitary neurosecretosomes are exclusively kappa. AB - Intact neurosecretosomes (NSS) from bovine posterior pituitary were prepared and characterized. Ligand binding studies were performed, using 3H-[D-Ala2-D Leu5]enkephalin (DADL), 3H-etorphine and 3H-ethylketocyclazocine (EKC). The absence of specific binding of 3H-DADL and the inability of DADL to displace 3H etorphine, implies the absence of mu, delta, or DADL-suppressible benzomorphan ("kappa-2") sites. Self- and cross displacement studies for etorphine and EKC suggested receptor heterogeneity. EKC fails to displace - 20% of specific binding of etorphine. Mathematical modelling indicates the presence of three classes of sites. The present findings imply that bovine posterior pituitary opioid receptors are exclusively of the kappa type. PMID- 2893284 TI - Lineage-specific expression of a human beta-globin gene in murine bone marrow transplant recipients reconstituted with retrovirus-transduced stem cells. AB - Recombinant retroviral genomes encoding a chromosomal human beta-globin gene have been used to transduce murine haematopoietic stem cells in vitro. After permanent engraftment of lethally irradiated recipients with the transduced cells, the human beta-globin gene is expressed at significant levels only within the erythroid lineage. These results indicate that it is possible to obtain stable expression of exogenous chromosomal DNA sequences introduced into mature haematopoietic cells in vivo via stem cell infection, and that human disorders of haemoglobin production may be more feasible candidates for somatic cell gene therapy than previously suspected. PMID- 2893285 TI - Regulation of segment polarity genes in the Drosophila blastoderm by fushi tarazu and even skipped. AB - During the late cellular blastoderm stage of Drosophila embryo-genesis the segmentation genes engrailed, en, and wingless, wg, become expressed in two series of 14 stripes which will subsequently coincide with the anterior and posterior limits of each parasegment. Previous studies have shown that the establishment of the pattern of en stripes depends upon the activity of the homoeobox-containing pair-rule genes fushi tarazu, ftz and even skipped, eve. Here we show that these two genes also control the spatial expression of wg. Whereas ftz and eve behave as activators of en we find that both genes are required to repress wg expression, so that wg becomes expressed only in the narrow stripes of cells which come to separate the ftz and eve bands at the end of the blastoderm stage. In contrast, we propose that the precise positioning of the en stripes depends upon signals generated in a combinatorial manner by the overlaps between the ftz or eve domains and those of other pair rule genes, specifically odd paired, opa and paired, prd. PMID- 2893286 TI - Tumour necrosis factor-alpha in murine autoimmune 'lupus' nephritis. AB - The (NZB x NZW)F1 hybrid mouse develops a severe autoimmune disease similar to systemic lupus erythematosus in humans. Both the human and murine form of the disease show strong associations with alleles of the major histocompatibility complex (MHC) gene products. The severe form of the disease found in F1 mice is due, in part, to dominant NZW gene(s) mapping with the H-2 complex (the murine MHC). Here we present evidence that the tumour necrosis factor (TNF-alpha) gene, which is located within the H-2 complex (the murine major histocompatibility complex), could be involved in the pathogenesis of lupus nephritis in F1 mice. Thus, a restriction fragment length polymorphism in the TNF-alpha gene correlates with the reduced levels of TNF-alpha produced by NZW mice. Furthermore, replacement therapy with recombinant TNF-alpha induces a significant delay in the development of the nephritis. PMID- 2893287 TI - Whose own goal? PMID- 2893288 TI - Global cooperation pledged after first AIDS summit. PMID- 2893290 TI - Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. AB - Amyloid B-protein/amyloid A4 is a peptide present in the neuritic plaques, neurofibrillary tangles and cerebrovascular deposits in patients with Alzheimer's disease and Down's syndrome (trisomy 21) and may be involved in the pathogenesis of Alzheimer's disease. Recent molecular genetic studies have indicated that amyloid protein is encoded as part of a larger protein by a gene on human chromosome 21 (refs 6-9). The amyloid protein precursor (APP) gene is expressed in brain and in several peripheral tissues, but the specific biochemical events leading to deposition of amyloid are not known. We have now screened complementary DNA libraries constructed from peripheral tissues to determine whether the messenger RNA encoding APP in these tissues is identical to that expressed in brain, and we identify a second APP mRNA that encodes an additional internal domain with a sequence characteristic of a Kunitz-type serine protease inhibitor. The alternative APP mRNA is present in both brain and peripheral tissues of normal individuals and those with Alzheimer's disease, but its pattern of expression differs from that of the previously reported APP mRNA. PMID- 2893289 TI - A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. AB - The amyloid proteins isolated from neuritic plaques and the cerebrovasculature of Alzheimer's disease are self-aggregating moieties termed A4 protein and beta protein, respectively. A putative A4 amyloid precursor (herein termed A4(695] has been characterized by analysis of a human brain complementary DNA. We report here the sequence of a closely related amyloid cDNA, A4(751), distinguished from A4(695) by the presence of a 168 base-pair (bp) sequence which adds 57 amino acids to, and removes one residue from, the predicted A4(695) protein. The peptide predicted from this insert is very similar to the Kunitz family of serine proteinase inhibitors. The two A4-specific messenger RNAs are differentially expressed: in a limited survey, A4(751) mRNA appears to be ubiquitous, whereas A4(695) mRNA has a restricted pattern of expression which includes cells from neuronal tissue. These data may have significant implications for understanding amyloid deposition in Alzheimer's disease. PMID- 2893291 TI - Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. AB - Alzheimer's disease is characterized by cerebral deposits of amyloid beta-protein (AP) as senile plaque core and vascular amyloid, and a complementary DNA encoding a precursor of this protein (APP) has been cloned from human brain. From a cDNA library of a human glioblastoma cell line, we have isolated a cDNA identical to that previously reported, together with a new cDNA which contains a 225 nucleotide insert. The sequence of the 56 amino acids at the N-terminal of the protein deduced from this insert is highly homologous to the basic trypsin inhibitor family, and the lysate from COS-1 cells transfected with the longer APP cDNA showed an increased inhibition of trypsin activity. Partial sequencing of the genomic DNA encoding APP showed that the 225 nucleotides are located in two exons. At least three messenger RNA species, apparently transcribed from a single APP gene by alternative splicing, were found in human brain. We suggest that protease inhibition by the longer APP(s) could be related to aberrant APP catabolism. PMID- 2893292 TI - DNA fingerprinting to be used for British immigrants? PMID- 2893293 TI - Comparison of simian immunodeficiency virus isolates. AB - Information on the extent of genetic variability among non-human primate lentiviruses related to human immunodeficiency virus (HIV) is sorely lacking. Here we describe the isolation of two molecular clones from the simian immunodeficiency virus (SIV) and their use to derive restriction endonuclease maps of five SIV isolates from rhesus macaques and one from a cynomolgus macaque. Although similar, all six viral isolates are readily distinguishable; the single isolate from a cynomolgus macaque is the most different. The restriction endonuclease map of one macaque isolate (SIVMAC-251) is identical to that published by others for STLV-IIIAGM of African green monkeys and for HTLV-IV of humans. Nucleotide sequences from the envelope region of cloned SIVMAC-251 have more than 99% identify to previously published sequences for STLV-IIIAGM (refs 2, 4) and HTLV-IV (ref. 4). These results and other observations provide strong evidence that isolates previously referred to as STLV-IIIAGM and HTLV-IV by others are not authentic, but were derived from cell cultures infected with SIVMAC-251. PMID- 2893294 TI - An H+-ATPase in opposite plasma membrane domains in kidney epithelial cell subpopulations. AB - Vectorial solute transport by epithelia requires the polarized insertion of transport proteins into apical or basolateral plasmalemmal domains. In the specialized intercalated cells of the kidney collecting duct, the selective placement of an apical plasma membrane proton-pumping ATPase (H+-ATPase) and of a basolateral membrane anion-exchange protein results in transepithelial proton secretion. It is currently believed that amino-acid sequences of membrane proteins contain critical signalling regions involved in sorting these proteins to specific membrane domains. Recently, it was proposed that intercalated cells can reverse their direction of proton secretion under different acid-base conditions by redirecting proton pumps from apical to basolateral membranes, and anion exchangers from basolateral to apical membranes. But others have found that antibodies raised against the red cell anion-exchange protein (Band 3) only labelled intercalated cells at the basolateral plasma membrane, providing evidence against the model of polarity reversal. In this report, we have examined directly the distribution of proton pumps in kidney intercalated cells using specific polyclonal antibodies against subunits of a bovine kidney medullary H+ ATPase. We find that some cortical collecting duct intercalated cells have apical plasma membrane proton pumps, whereas others have basolateral pumps. This is the first direct demonstration of neighbouring epithelial cells maintaining opposite polarities of a transport protein. Thus, either subtle structural differences exist between proton pumps located at opposite poles of the cell, or factors other than protein sequence determine the polarity of H+-ATPase insertion. PMID- 2893296 TI - Pharmacologic differentiation between pre- and postjunctional alpha 2 adrenoceptors by SK&F 104078. AB - Most alpha 2-adrenoceptor antagonists do not discriminate between pre- and postjunctional alpha 2-adrenoceptors, and this has led to the commonly held belief that pre- and postjunctional alpha 2-adrenoceptors may represent one homogeneous population of receptors. SK&F 104078 has been shown to be a potent antagonist at postjunctional alpha 2-adrenoceptors at concentrations that do not block prejunctional alpha 2-adrenoceptors. Thus, SK&F 104078 is a competitive postjunctional alpha 2-adrenoceptor antagonist in canine and rabbit saphenous veins, canine saphenous artery and human platelet with a dissociation constant of approximately 100 nmol/l. Conversely, SK&F 104078 is inactive as a prejunctional alpha 2-adrenoceptor antagonist in atria from dog, guinea pig, rabbit and rat, and in guinea-pig ileum at concentrations up to 10,000 nmol/l. Likewise, SK&F 104078 has the ability to block postjunctional arterial alpha 2-adrenoceptors in vivo in the pithed rat at doses that do not inhibit prejunctional alpha 2 adrenoceptors in the same model. The results suggest that pre- and postjunctional alpha 2-adrenoceptors may not represent one homogeneous class, but rather are discrete subtypes of the alpha 2-adrenoceptor that may be differentiated by SK&F 104078. PMID- 2893295 TI - Inhibition of vasoconstriction to cirazoline by calcium-entry blockade after phenoxybenzamine in rat perfused hindquarters. AB - The effects of phenoxybenzamine and benextramine were assessed with respect to the vasoconstriction to cirazoline in rat perfused hindquarters. Experiments were performed with and without restriction of inward calcium flux by addition of nifedipine (10(-9)-10(-6) M) to the standard physiological solution (PS), or by omission of calcium chloride from the PS. Addition of nifedipine or omission of Ca2+ did not affect the maximal response or potency of the selective but partial alpha 1-adrenoceptor agonist, cirazoline in rat perfused hindquarters. Upon pretreatment with phenoxybenzamine (0.03-30 micrograms/kg, i.v. at -1 h) or benextramine (1 mg/kg, i.v. at -2 h) both the slope and the maximal response to cirazoline were depressed. After phenoxybenzamine but not after benextramine the maximal response to cirazoline was depressed further upon addition of nifedipine or omission of Ca2+ from the PS. It is concluded that phenoxybenzamine selectively inhibits that part of the alpha 1-adrenoceptor mediated vasoconstriction that is independent of extracellular calcium, thereby unmasking a calcium-entry sensitive mechanism of vasoconstriction to cirazoline. PMID- 2893297 TI - Analysis of the receptors mediating vascular actions of bradykinin. AB - A range of bradykinin (BK) analogues was assessed for their ability to antagonise the action of BK on rabbit jugular vein, a B2-receptor containing tissue, and compared with their action against BK-induced increases in skin vascular permeability in the rabbit and rat. The results demonstrate that modification of the BK (nonapeptide) structure by the insertion of certain D-amino acids in positions 5, 7 and 8 in addition to elongation of the amino terminal resulted in compounds with potent antagonistic action against BK on rabbit jugular vein and rabbit skin vascular permeability. The same BK analogues did not antagonise the action of BK on rat skin vascular permeability. It is concluded that the kinin receptor mediating an increase in vascular permeability in the rabbit is the same as that mediating contraction of the rabbit jugular vein in vitro, that is the B2 type. The kinin receptor mediating an increase in skin vascular permeability in the rat is difficult to classify but does not appear to be of the B2 type. PMID- 2893298 TI - Interactions of the histamine H2-receptor antagonist etintidine with rat liver cytochrome P-450: a comparison with cimetidine. AB - The two imidazole histamine H2-receptor antagonists etintidine and cimetidine interact with the rat liver microsomal cytochrome P-450. From type II spectral changes follows that the affinity of rat liver microsomal preparations for etintidine is about 5 times as high as for cimetidine when comparing both high and low affinity binding sites. After pretreatment with phenobarbital etintidine inhibited benzphetamine N-demethylation competitively (app. Ki: 4.0 mmol/l). Cimetidine inhibited benzphetamine N-demethylation in the same range. After pretreatment with phenobarbital both drugs inhibited the oxidation of benzo(a)pyrene for which etintidine showed a higher inhibitory potency than cimetidine. However, this oxidation could not be inhibited when microsomes of 5,6 benzoflavone pretreated rats were used. After pretreatment with 5,6-benzoflavone only etintidine but not cimetidine inhibited the O-deethylation of ethoxyresorufin competitively (app. Ki: 0.2 mmol/l). Etintidine and cimetidine were metabolized by rat liver microsomes to their corresponding sulphoxides. In conclusion, etintidine may cause mainly the same drug interactions as cimetidine but seems to be a more potent inhibitor. PMID- 2893299 TI - Jellyfish envenomation. PMID- 2893300 TI - [Sulfasalazine as an antirheumatic agent; a review of the literature]. PMID- 2893301 TI - [Drugs in angina pectoris]. PMID- 2893303 TI - DNA rearrangement as a marker of B and T cell malignancies. PMID- 2893302 TI - [Benzodiazepine prescriptions at a university clinic]. PMID- 2893304 TI - Changes in the brain in aging and Alzheimer's disease assessed by neuronal counts. AB - Changes in the magnitude of neuronal loss, which represent the end point of neuronal degeneration, are controversial and of limited utility as a measure of functional decline in aging and Alzheimer's disease (AD). Changes in the size of neurons and organelles, in the distributions of dendritic and synaptic fields, and in the relationships between neurons and the transmitter substances they produce, may be more useful in that they estimate changes in neuronal function prior to neuronal loss. The quantitative assessment of metabolic change in individual neurons by measuring histochemical reactivity, or more directly measuring enzyme activity or the amounts of its products might more reliably reflect degenerative changes associated with aging or AD, prior to the loss of neurons. PMID- 2893305 TI - New approaches to quantitative neuropathology: multivariate analysis of morphologic and neurochemical measures. AB - The excellent review by Coleman and Flood on neuropathological changes in normal aging and Alzheimer's disease highlights the need for development and application of computer-assisted image analysis to the study of neurons in these conditions. The morphological and neurochemical changes in normal and pathological aging require quantitation and statistical analysis that can be best performed with the assistance of the image and data processing capabilities of the computer. Advanced image processing systems are being developed to identify and classify neurons according to several intelligently chosen visual features, apply discriminant analysis and population statistics to this data, and correlate this information to other neurochemical measurements as well as the clinical history of the patient. Techniques such as immunocytochemistry, receptor autoradiography and in situ hybridization produce information-rich images of the distribution of proteins and nucleic acids in tissue slices that can be analyzed by this approach. PMID- 2893306 TI - Qualitative and quantitative changes in normal aging and Alzheimer's disease. AB - Qualitative changes in normal aging and Alzheimer's disease (AD) are as important as quantitative changes. Although qualitative changes do not c-vary with quantitative differences in every respect, quantitative changes, nevertheless, often accurately reflect qualitative changes. Moreover, the complementary use of each provides a more detailed characterization of brain changes with aging and AD. The quantitative and qualitative changes of choline acetyltransferase, as well as somatostatin-containing neurons and dendrites, in human cortex are described as examples of this. PMID- 2893307 TI - Tyrosine hydroxylase mRNA is increased by hyperosmotic stimuli in the paraventricular and supraoptic nuclei. AB - In situ hybridization histochemistry was used to locate cells containing tyrosine hydroxylase (TH) mRNA in the hypothalami of salt-loaded and Brattleboro rats. The hyperosmotic plasma conditions found in these animals, as compared to control animals, was associated with an increase in detectable TH mRNA-producing cells in the paraventricular and supraoptic nuclei. These results suggest that dopamine synthesized by neurons of those nuclei may participate in the regulation of neuropeptide synthesis and release within the nuclei and the posterior pituitary. PMID- 2893308 TI - Immunoreactive dynorphin is regulated by estrogen in the rat anterior pituitary. AB - The pituitary and hypothalamic content of dynorphin was determined by radioimmunoassay and characterized by high-performance liquid chromatography (HPLC) in adult female Sprague-Dawley rats, intact and ovariectomized with and without estrogen treatment. Animals were given estradiol benzoate, or vehicle (oil) by six daily intramuscular injections. Anterior pituitary content of immunoreactive (ir)-dynorphin in ovariectomized rats was approximately twice that of intact animals, and consisted of a single HPLC peak co-eluting with dynorphin 32. Administration of estradiol benzoate (0.06-6 micrograms/day) caused a marked decrease of ir-dynorphin in the anterior lobe of castrate female rats, with a half-maximal effect at 0.2 microgram/day; levels were restored to those seen in intact animals with 6 micrograms estradiol benzoate per day, an effect which was not influenced by concomitant administration of progesterone (1 mg/day), or bromocriptine (100 micrograms/day). In the hypothalamus and neuro-intermediate lobe multiple peaks of immunoreactive dynorphin were seen, coeluting with dynorphin A 1-8, dynorphin A 1-17 and dynorphin 32. Neither castration nor estrogen treatment altered ir-dynorphin content in these tissues. These findings suggest that the ovary exerts a specific modulating influence on AP ir-dynorphin in the rat, and that in addition this inhibition appears to be mediated by ovarian estrogen. PMID- 2893309 TI - The endogenous kappa agonist, dynorphin(1-13), does not alter basal or morphine stimulated dopamine metabolism in the nigrostriatal pathway of the rat. AB - Dopaminergic pathways in the brain of the rat have been shown to possess both mu and delta opioid regulatory inputs. In contrast, studies with synthetic kappa opiate agonists have demonstrated a lack of regulation of these dopaminergic systems by kappa opioids. The present authors have extended these observations, to study the effects of the putative endogenous kappa agonists, dynorphin (1-13), on the metabolism of nigrostriatal dopamine in the rat after intraventricular administration. The stability of the intraventricularly administered dynorphin was confirmed in vivo by measuring corticosterone in plasma in the same animals utilized for neurochemical analyses. This is a neuroendocrine parameter which has been demonstrated to possess central regulation by independent mu and kappa receptors. While morphine given parenterally elevated both the level of corticosterone in plasma and the central metabolism of dopamine, neither the parenteral administration of the kappa agonist, U50488H, or the intraventricular administration of dynorphin altered central metabolism of dopamine. However, in both cases, levels of corticosterone in plasma were dramatically elevated, clearly demonstrating the bioavailability of the kappa agonists. The actions of morphine on the metabolism of dopamine, which can be antagonized by pretreatment with synthetic kappa agonists, were not antagonized by dynorphin(1-13). To summarize, the present data indicated that the nigrostriatal dopaminergic pathway in the rat lacks kappa opioid regulation. In addition, while synthetic kappa agonists also possessed mu antagonist actions, the endogenous ligand, dynorphin, did not. PMID- 2893310 TI - Is ganglionic transmission through nicotinic receptors essential for the peristaltic reflex in the guinea-pig ileum? AB - Peristaltic reflex activity in the guinea-pig isolated ileum was elicited by slow intraluminal infusion of Tyrode solution. The reflex was abolished by the ganglionic blocking drug hexamethonium. However, in more than half of the preparations, the peristaltic reflex was restored by the opioid antagonist naloxone. Hexamethonium-resistant peristaltic waves were blocked by tetrodotoxin or atropine. These data suggest that ganglionic transmission through nicotinic acetylcholine receptors may not be essential for the peristaltic reflex provided that the inhibitory action of endogenous opioids has been eliminated. PMID- 2893311 TI - Effect of ceruletide on discriminated avoidance behavior in rats. AB - To clarify the central action of peripherally administered ceruletide, we examined the effects of ceruletide and four different classes of neuroleptics, i.e. haloperidol, chlorpromazine, oxypertine and sulpiride, on the discriminated avoidance response (DAR) in rats. Ceruletide and sulpiride did not suppress the DAR over a broad range of doses, whereas other three neuroleptics caused a dose related decrease in both avoidance and response rates. In addition, the combined administration of ceruletide (100 micrograms/kg s.c.) and neuroleptics at critical doses that suppress the DAR caused a significant reduction in the avoidance rate without affecting the response rate, compared with neuroleptics alone. These findings suggest that ceruletide influences the central dopaminergic system, potentiating the central effects of neuroleptics and producing the favorable therapeutic effects observed in the clinical trials. PMID- 2893312 TI - Striatal neurochemistry of dynorphin-(1-13): in vivo electrochemical semidifferential analyses. AB - The striatal neurochemistry of dynorphin-(1-13) was studied by simultaneously measuring extracellular dopamine and serotonin voltammetrically and in vivo after the injection of dynorphin-(1-13) to male Sprague-Dawley rats. The subcutaneous administration of dynorphin-(1-13), at a dose (1.5 mg/kg), known to exert CNS mediated behavioral effects, caused a statistically significant decrease in extracellular dopamine and a statistically significant increase in extracellular serotonin from rat anterior striatum. These parallel and opposite effects of dynorphin-(1-13) on these biogenic amines occurred gradually during a three hour time course. Maximal effects on dopamine (55%) and on serotonin (62%) occurred at the end of the three hour period of study. Mean effects on dopamine and serotonin (35% and 42% respectively) were averaged from scan results over the three hour period of study; the results were significantly different from control values. Dose response studies showed that a lower dose of dynorphin-(1-13) (0.5 mg/kg sc) had little or no effect on the alteration of these biogenic amines from striatum. The highest dose of dynorphin-(1-13) studied, (3.0 mg/kg sc), predictably and significantly altered extracellular biogenic amines. The dose response, however, was not incremental. The results are consistent with the role of dynorphin-(1-13) as a neuromodulatory peptide. The results further support the concept that the neuromodulatory role of dynorphin-(1-13) may take place through neurotransmitter regulation. The data suggest that the function of dynorphin-(1-13) may be a presynaptic modulation of neurotransmission in striatum. PMID- 2893313 TI - Prolonged excitation of individual neocortical neurons, structure of background impulse activity. AB - The background impulse activity of individual neurons was recorded extracellularly in the cerebral cortex of the cat during the prolonged microionophoretic delivery to these neurons of L-glutamate. Glutamate ionophoresis ensured the transition of the neuron to an elevated, but stable level of activation. An autocorrelation analysis of the trains of impulses showed that in spite of the multiple rise in the average discharge frequency, the type of background impulse activity and the periods of increased and reduced probability of discharges for the most part remained constant. The obtained data indicate that an individual cell is unable to influence substantially the interneurons connected with it, while the type of background activity of a neuron is determined primarily by the level of activation of the cellular ensemble incorporating this neuron. PMID- 2893314 TI - Intraventricular bethanechol infusion for Alzheimer's disease: results of double blind and escalating-dose trials. AB - Ten patients with biopsy-proven Alzheimer's disease (AD) received low-dose (0.35 mg/d) intraventricular bethanechol, a muscarinic agonist, and saline placebo in a 24-week double-blind crossover design. Eight of these ten patients later participated in an open escalating-dose (to 1.75 mg/d) trial of bethanechol. Patients' drug responses were assessed by neuropsychological examination and informant measures of activities of daily living, mood disturbance, and abnormal behavior. Bethanechol appears to have a narrow therapeutic window for positive effects; low doses did not reliably alter patient functioning, moderately increased doses appeared to have a palliative effect on patient mood and behavior, and the highest dose was detrimental to patient functioning. Bethanechol does not appear to ameliorate the dementia of AD, but may exert a mildly positive effect on patient behavior and mood. PMID- 2893315 TI - Intraventricular bethanechol in Alzheimer's disease: a continuing controversy. PMID- 2893316 TI - Central respiratory drive-related activity in sympathetic nerves of the rat: the regional differences. AB - In halothane-anaesthetized, vagotomized, SA-denervated rats, the activity of various sympathetic nerves has been analyzed with respect to phrenic nerve discharge (an indicator of central respiratory drive (CRD)). The cervical and lumbar sympathetic nerves had maximal activity following, and were least active during phrenic nerve discharge. In contrast, the splanchnic, cardiac, renal and adrenal nerves exhibited their activity peak during phrenic nerve discharge (i.e. inspiration). Similar activity profiles were observed after ganglion blockade in the mixed pre- and postganglionic fibre preparations. These observations indicate that it is the subpopulations of preganglionic neurones and the proportional contribution of each to whole-nerve activity which give rise to the differences in CRD-related activity profiles between nerves. PMID- 2893317 TI - Long-lasting potentiation produced by a phorbol ester in the hippocampus of the anaesthetized rat is not associated with a persistent enhanced release of excitatory amino acids. AB - The relationship between the long-lasting enhancement of synaptic transmission produced by a phorbol ester and the release of endogenous excitatory amino acids has been investigated in the CA1 hippocampal region of the anaesthetized rat. Using the push-pull technique, the concentration of glutamate and aspartate was assayed in the perfusate by high-pressure liquid chromatography. Application of phorbol 12-13 diacetate produced a long lasting enhancement of the field excitatory postsynaptic potential (EPSP) (over 2 h). This was associated with a brief (10 min) significant increase in the release of glutamate and aspartate. However, subsequently the levels of the amino acids in the perfusate were not different from the pre-drug (control) levels although the field EPSP was still enhanced. It is concluded that the long-lasting enhancement produced by phorbol ester is not due to a persistent increase in the release of excitatory amino acids. PMID- 2893318 TI - Continuous glutamate leakage from brain cells is balanced by compensatory high affinity reuptake transport. AB - The glutamate (and aspartate) uptake blocker threo-3-hydroxyaspartate (20 microM) was added to superfusion fluids employed for in vivo microdialysis of corpus striatum, and to incubation medium for striatal slices (5 microM). In vivo it caused an increase in glutamate and aspartate concentrations in the superfusion fluid. In vitro it caused increases in the levels of glutamate, aspartate, GABA, taurine and glutamine in the incubation fluid. Tetrodotoxin (1 microM) did not influence the rises in glutamate or aspartate. It is concluded from these results that there is a continuous outward leakage of glutamate, and aspartate, from neural cells which is normally balanced by an inward flux due to reuptake processes. This leakage is distinct from synaptic release of these substances due to spike activity, since tetrodotoxin added to striatal slices did not diminish the action of threo-3-hydroxyaspartate. The significance of the findings for mechanisms leading to ischaemic or hypoxic brain damage, and basic mechanisms in epilepsy is discussed. PMID- 2893320 TI - Comparison of kynurenic acid and 2-APV suppression of epileptiform activity in rat hippocampal slices. AB - The N-methyl-D-aspartate (NMDA) receptor blocker 2-amino-5-phosphonovaleric acid [+/-)-2-APV) and kynurenic acid both suppressed spontaneous epileptiform burst discharges in the CA3 region of rat hippocampal slices. When the bursts were induced by perfusion with magnesium-free medium (+/-)-2-APV was the more potent inhibitor (ED50 66 microM for (+/-)-2-APV and 110 microM for kynurenate). When bursts were induced by picrotoxin, kynurenate was more potent with an ED50 of 132 microM, compared with 290 microM for (+/-)-2-APV. Both antagonists were selective inhibitors of responses to NMDA when examined against excitations induced by NMDA, kainate and quisqualate applied by microiontophoresis onto CA3 pyramidal cells. The results may indicate a complex receptor profile for endogenous compounds involved in epileptiform bursts, or the existence of non-pyramidal cells bearing non-NMDA receptors sensitive to kynurenic acid. PMID- 2893319 TI - Glutamate recognition sites in human fetal brain. AB - We used in vitro autoradiography with [3H]glutamate to examine the distribution of glutamate recognition sites in 18 and 21 week gestation human fetal brains. We found a wide distribution of [3H]glutamate binding in both specimens, in a pattern distinct from that reported in adult brain using the same autoradiographic methods. In fetal brain, prominent [3H]glutamate binding was evident in hippocampal formation, caudate-putamen, globus pallidus, subthalamic nucleus, reticular nucleus of thalamus and substantia innominata. PMID- 2893321 TI - Myocardial abscess complicating acute myocardial infarction. PMID- 2893322 TI - [Improving training in ophthalmology in the light of the decisions of the 27th Party Congress and a project of the Central Committee of the CPSU with regard to the reorganization of higher and secondary special education in the country]. PMID- 2893323 TI - [New developments in the theory of homeotic genes]. PMID- 2893324 TI - An evaluation of etiologic factors in 382 patients treated in a postgraduate endodontic program. AB - A survey was completed to determine and to evaluate the reason for endodontic treatment performed by endodontic residents at the Baltimore College of Dental Surgery, University of Maryland at Baltimore. On the basis of patient data and the reasons for endodontic treatment, as stated by the treating residents, the results showed that necrotic pulp and irreversible pulpitis were the most frequent reasons for endodontic therapy. Other reasons for treatment included restorative considerations, retreatment, and trauma. The majority of cases involved posterior teeth, and the average age of patients was 40.0 years. The frequency by arch demonstrated approximately equal distribution between maxillary (54.8%) and mandibular (45.2%) teeth. A total of 224 (58.6%) of the 382 patients surveyed had preoperative pain. PMID- 2893325 TI - Endogenous opioid peptides and human reproduction. PMID- 2893326 TI - Antinociceptive and 'neurotoxic' actions of somatostatin in rat spinal cord after intrathecal administration. AB - In the present investigation, the antinociceptive effect of somatostatin (SST) was assessed after intrathecal injection in rats. It was found that the peptide caused antinociception, hind limb paralysis and neuronal damage of the spinal cord in a dose-dependent manner. The threshold dose for antinociception was lower (approximately 10 micrograms) than that (approximately 30 micrograms) giving rise to chronic motor impairment associated with necrotic changes and loss of an immunohistochemical marker for motoneurons in the spinal cord. It is concluded that the 'neurotoxic' potential of SST should be considered in further clinical trials. PMID- 2893327 TI - HLA antigens associated to amoebic abscess of the liver in Mexican mestizos. AB - Worldwide prevalence of amoebiasis is estimated at 4 x 10(8) cases/year, yet only one of about 300 individuals harbouring Entamoeba histolytica suffers tissue invasion and these cases are mostly concentrated in certain areas of Asia, Africa and Latin America. Patients with amoebic abscess of the liver (AAL) represent only a small fraction of that. These contrasting figures have been tentatively explained on the one hand through variations in sex, immunocompetence, nutritional and other socioeconomic features of the host, and on the other hand through differences in parasite virulence. In order to explore a possible association between the major histocompatibility complex (MHC) and AAL susceptibility, we studied the HLA profile in 31 Mexican mestizos with AAL and compared it to race and socioeconomically matched controls. Mexican mestizo patients with AAL revealed a significant increase in HLA-Bw16 and HLA-DR3 which could suggest an HLA-related susceptibility to liver invasion by E. histolytica. PMID- 2893328 TI - The undescended testis. PMID- 2893330 TI - Unsuspected urological anomalies in asymptomatic cryptorchid boys. AB - In a period of 6 years 144 asymptomatic boys with cryptorchidism, of mean age 7 +/- SD 3.5 years, underwent orchiopexy. None of these boys referred to a history of a known urological anomaly, urinary tract infection, haematuria, palpable mass in the renal region, bladder extrophy, epispadias, hypospadias or anorectal malformation. On the third day after orchiopexy and intravenous pyelography was done in every boy following testicular protection against irradiation. Ultrasonic investigation was not available at that time. There were minor urological abnormalities in 36 (25%) boys and major ones in 8 (5.5%) boys. A major anomaly is defined as one resulting in significant loss of renal substance (one case of single kidney and three cases of unilateral renal hypoplasia), or requiring surgical correction for conservation of the renal substance (one case of ureterocele, two cases of pelviureteric stenosis and one case of vesicoureteric stenosis with ipsilateral hydronephrosis). The unsuspected major urological abnormalities are usually ipsilateral to the more undescended testis. They may be associated with a hernia and are more frequent in bilateral cryptorchidism. In conclusion we encourage the routine use of IVP, or ultrasonic investigation or dynamic renal scanning (99mTc-DTPA), if it is possible, in all patients undergoing orchiopexy for the detection of an unsuspected major renal anomaly. PMID- 2893329 TI - Inflammatory bowel disease in children. AB - Ulcerative colitis and Crohn's disease are chronic intestinal disorders with diverse presentations that must be familiar to pediatricians. The subtlety of clinical signs and symptoms may be overshadowed by extraintestinal complications. An awareness of diagnostic techniques and the necessity of an integrated approach of medical and surgical management is emphasized. Potential complications may affect prognosis and require their own specific therapy. The management of these disorders entails an individualized assessment of the extent and severity of intestinal involvement, extraintestinal complications, as well as ongoing medical, nutritional, and emotional support. PMID- 2893331 TI - [The GnRH test reveals changes in readiness of testosterone and estradiol secretion in boys with bilateral cryptorchism]. PMID- 2893332 TI - [Cryptorchism (data of the Pediatric Surgery Clinic in Lodz)]. PMID- 2893333 TI - Osteomyelitis secondary to trauma or infected contiguous soft tissue. AB - Nonhematogenous osteomyelitis (NHO) occurred in 24 pediatric patients (ages 8 months to 18 years; median, 14 years; 23 male) admitted from 1980 to 1985. Predisposing factors included compound fracture (12), deep decubiti (4) and foot puncture (3). Infection involved tibia (7), foot bones (6), proximal femur (3) and ulna (2). Patients presented with drainage (64%), pain or tenderness (44%) and fever (32%) lasting for 1 to 180 days (median, 10 days). In 24% both white blood cell count and erythrocyte sedimentation rate were normal. Initial radiographs were nondiagnostic in 42% after compound fractures. Bone cultures were positive in 15 of 18 (83%) patients for: Staphylococcus aureus (9), Staphylococcus epidermidis (2), Pseudomonas aeruginosa (4), Escherichia coli (2), Enterobacter sp. (2), Streptococcus faecalis, Serratia sp., Klebsiella pneumoniae, Achromobacter xylosoxidans, Aeromonas hydrophila and Pseudomonas fluorescens (1 each). Wound cultures failed to predict bone culture results in 12 of 16 patients (75%). NHO recurred in 8 of 19 patients (42%) despite intravenously administered antibiotics for greater than 28 days and debridement in 7 of 8 patients. The indolent nature of NHO complicates diagnosis, especially in patients with recent compound fractures. Only prompt bone culture can confirm the presence of NHO and reliably guide antimicrobial therapy. PMID- 2893334 TI - [Somatostatin, what are its uses?]. AB - Somatostatin has several effects on the secretions of the gastrointestinal tract. The assessment of therapeutic use is based on literature review. The rebound and escape phenomena are the main problems in the clinical use of somatostatin and their prevention is perhaps possible by the prescription of a long-acting analogue in an intermittent mode of administration. PMID- 2893336 TI - The regulation of beta-adrenoceptor function. Pharmacological and biochemical aspects of receptor desensitization and receptor down-regulation. PMID- 2893335 TI - Studies on nasal drug delivery. PMID- 2893337 TI - cAMP and beta-adrenergic stimulation of rat alveolar epithelium. Effects on fluid absorption and paracellular permeability. AB - The absorption of fluid (bicarbonate-buffered Ringer with 10 mmol/l glucose) instilled into rat lungs is a Na+-coupled process that takes place through two apical transport systems: an amiloride-sensitive Na+ transport and a Na+-glucose co-transport. Fluid absorption in isolated, perfused rat lungs and the permeability to 3H-mannitol of alveolar epithelium were studied in control conditions and during stimulation of the alveolar epithelium by cAMP or isoproterenol. cAMP led to a threefold increase in the rate of fluid absorption and to an increase in the paracellular permeability. A similar response was found following beta-adrenergic stimulation obtained with isoproterenol in the perfusate. The increase in fluid transport was due to enhancement of the amiloride-sensitive component of Na+ transport. The Na+-glucose co-transport which accounts for about 60% of fluid absorption in control conditions was depressed, possibly as a consequence of a depolarization of the apical alveolar cell membrane. Fluid absorption was reduced by 40% by apical amiloride (10(-4) mol/l) in control lungs and to an even larger extent in isoproterenol-stimulated lungs; it was completely abolished by amiloride in cAMP stimulated lungs. Since the Na+-glucose co-transport was still operative, this suggests that a secretory process was triggered. This was confirmed in experiments in which both kinds of transport were inhibited with a combination of amiloride and glucose-free Ringer. In these conditions fluid balance was zero in unstimulated lungs whilst fluid entry into alveoli was observed in isoproterenol and cAMP stimulated lungs. PMID- 2893340 TI - KGB: a single buffer for all restriction endonucleases. PMID- 2893339 TI - 5'-flanking sequence of mouse glutathione S-transferase Ya gene. PMID- 2893338 TI - Cardiac alpha-1 adrenoceptors are not involved in heart rate control of the anaesthetized dog. AB - To study the possible role of cardiac postsynaptic alpha-1 adrenoceptors in heart rate control of the anaesthetized open-chest dog we injected a specific alpha-1 agonist (amidephrine) into the right coronary artery or stimulated electrically the right stellate ganglion. Reflex influences were minimized by bilateral cervical vagotomy and de-afferentiation of both stellate ganglia. Activation of alpha-2, beta- and muscarinic receptors was prevented by intravenous administration of yohimbine, propranolol and atropine, respectively. Since alpha 1 receptor stimulation could affect heart rate indirectly via coronary constriction, a continuous intracoronary infusion of adenosine (0.25 mg/kg/h) was given. Amidephrine did not affect heart rate at the lower dose (1-10 microgram). After the highest dose (100 micrograms) the maximum variation in heart rate was an increase of 2.2 +/- 1.1 bpm at 3 min after injection (mean +/- SEM; P less than 0.05). This slight cardioacceleration was simultaneous with an aortic pressure rise of 13.8 +/- 3.4 mm Hg and it was abolished by alpha-1 blockade with prazosin (1 mg/kg i.v.). After propranolol (1 mg/kg +0.5 mg/kg/h) the residual positive chronotropic effect of sympathetic stimulation (12.2 +/- 4.0 bpm) was not significantly altered (13.8 +/- 5.7 bpm) by prazosin administration. Similar results were recorded without adenosine infusion. We conclude that in the anaesthetized dog chronotropic effects directly mediated by alpha-1 adrenoceptors either do not exist or lack physiological significance. PMID- 2893342 TI - Isolation and mapping of a polymorphic DNA sequence MCT128.1 on chromosome 11 [D11S285]. PMID- 2893341 TI - Isolation and mapping of a polymorphic DNA sequence pHBI18P2 on chromosome 11 [D11S147]. PMID- 2893344 TI - Isolation and mapping of a polymorphic DNA sequence pEFZ18.2 on chromosome 14 [D14S17]. PMID- 2893343 TI - Isolation and mapping of a polymorphic DNA sequence pMHZ9 on chromosome 14 [D14S18]. PMID- 2893345 TI - Isolation and mapping of a polymorphic DNA sequence pMLJ14 on chromosome 14 [D14S13]. PMID- 2893346 TI - Isolation and mapping of a polymorphic DNA sequence pEFD33.2 on chromosome 12 [D12S14]. PMID- 2893347 TI - Isolation and mapping of a polymorphic DNA sequence pYNH15 on chromosome 12q [D12S17]. PMID- 2893348 TI - Isolation and mapping of a polymorphic DNA sequence pYNZ90.1 on chromosome 15 [D15S28]. PMID- 2893349 TI - Isolation and mapping of a polymorphic DNA sequence pHHH202 on chromosome 17 [D17S33]. PMID- 2893350 TI - Isolation and mapping of a polymorphic DNA sequence pYNH37.3 on chromosome 17p [D17S28]. PMID- 2893351 TI - Isolation and mapping of a polymorphic DNA sequence pMCT35.1 on chromosome 17p [D17S31]. PMID- 2893352 TI - Isolation and mapping of a polymorphic DNA sequence pRMU3 on chromosome 17q [D17S24]. PMID- 2893353 TI - Isolation and mapping of a polymorphic DNA sequence pRMU1 on chromosome 17q [D17S27]. PMID- 2893354 TI - Isolation and mapping of a polymorphic DNA sequence cEFD52 on chromosome 17q [D17S26]. PMID- 2893355 TI - Isolation and mapping of a polymorphic DNA sequence pHHH152 on chromosome 17q [D17S32]. PMID- 2893356 TI - MIF-1 and Tyr-MIF-1 augment GABA-stimulated benzodiazepine receptor binding. AB - Behavioral evidence in laboratory animals and human beings indicates possible links between the endogenous opiate and gamma-aminobutyric acid (GABA) benzodiazepine receptor systems, especially with regard to antagonistic properties. To assess possible interactions between endogenous opiate antagonists and benzodiazepine receptor binding, we evaluated the effects of the peptides MIF 1 and Tyr-MIF-1 on benzodiazepine receptor binding in mouse brain membranes. Neither peptide affected receptor binding in cortex over a broad dose range, but both peptides significantly augmented GABA-stimulated benzodiazepine receptor binding at GABA concentrations of 10(-8) and 10(-7) M. Rosenthal-Scatchard analysis indicated that the increase in binding was largely due to increased apparent affinity. Both peptides augmented GABA-enhanced binding at low doses (MIF-1 10(-11) M, Tyr-MIF-1 10(-13) M) with decreased effects at higher doses. In cerebellum and brainstem, MIF-1 tended to enhance GABA-stimulated binding but Tyr MIF-1 was inactive. These results indicate benzodiazepine-opiate and benzodiazepine-peptide interactions. PMID- 2893357 TI - [D-Ala2, (F5) Phe4]-dynorphin 1-13-NH2 (DAFPHEDYN): a potent analog of dynorphin 1-13. AB - Intracerebroventricular administration of the dynorphin analog, [D-Ala2,(F5)Phe4] dynorphin 1-13-NH2 (DAFPHEDYN) in rats produced diuresis and profound analgesia. Both effects were antagonized by central administration of naltrexone or naloxone. Intravenous administration of 10, 25, and 50 mg/kg of DAFPHEDYN failed to induce diuresis. The increased potency of DAFPHEDYN was apparent from the failure of an equal dose of the parent compound (dynorphin 1-13) to produce diuresis and the failure of [D-Ala2]-dynorphin 1-13-NH2 to produce analgesia. Radioligand binding studies indicated the DAFPHEDYN retains the same degree of kappa selectivity as the parent compound (dynorphin 1-13) though a drop in affinity occurred. DAFPHEDYN may be of significant interest because it retains the essential pharmacology of the parent compound and exhibits marked in vivo potency. PMID- 2893358 TI - Effects of dynorphin (1-8) on movement: non-opiate effects and structure-activity relationship. AB - Cell bodies in the head of the caudate nucleus that synthesize prodynorphin peptides form a substantial projection to the substantia nigra pars reticulata (SNR). The discovery of this pathway suggested an involvement of prodynorphin products in motor control. The effects of unilateral nigral microinjections of prodynorphin products were tested in an in vivo circling model. Dynorphin (1-8), dynorphin (1-7), dynorphin (1-6), dynorphin (2-17) (des-Tyr-dynorphin), and Leu enkephalin induced spontaneous contralateral circling at 20 nmol doses. The effect of dynorphin (1-8) was dose dependent and was not blocked by pretreatment with naloxone or WIN 44,441-3. These findings clearly demonstrate the dynorphinergic involvement in nigral motor control which may consist of an opioid and a non-opioid component. PMID- 2893359 TI - Evidence for the presence of dihydro (reduced) somatostatin-14 in the guinea pig brain. AB - Analysis of somatostatin-like immunoreactivity (SLI) in guinea pig brain by HPLC and radioimmunoassay revealed an unexpected peak of SLI eluting at a retention time slightly later than standard somatostatin-14. The following evidence argues that this peak represents dihydro (H2) somatostatin-14. (1) The peak had the same retention time as standard [H2]somatostatin. (2) The possibility of a reduction artefact due to tissue processing was excluded by adding exogenous somatostatin 14 or 125I-labeled N-Tyr-somatostatin-14 to tissue and observing that no corresponding reduced peptides were generated. (3) Mild oxidation of brain extracts with H2O2 decreased, whereas mild reduction with dithiothreitol increased, the proposed peak of [H2]somatostatin. (4) Reaction of tissue extracts with iodoacetamide decreased the size of the proposed [H2]somatostatin peak but resulted in generation of a new peak co-eluting with standard carboxymethylated somatostatin-14. The proportion of the [H2]somatostatin peak in five brain regions, the hypothalamus, amygdala, cerebral cortex, brainstem and cerebellum, ranged from 6 to 20% of total SLI. The probability of somatostatin-14 existing endogenously in reduced or oxidized forms may have implications for its biological function in the guinea pig. PMID- 2893360 TI - Down-regulation of haloperidol-induced striatal dopamine receptor supersensitivity by active analogues of L-prolyl-L-leucyl-glycinamide (PLG). AB - Tardive dyskinesia, a clinical syndrome, is one of the major side effects of protracted treatment with neuroleptics in schizophrenic patients. Functional supersensitivity of striatal dopamine receptors is believed to contribute to the pathogenesis of schizophrenia and tardive dyskinesia. In a rodent model of neuroleptic-induced dopamine receptor supersensitivity, we investigated the efficacy of structurally modified analogues of PLG to down-regulate the striatal dopamine receptor supersensitivity as determined by alterations in [3H]spiroperidol binding to striatal membranes in vitro. The PLG analogue, L prolyl-L-leucyl-(+)-thiazolidine-2-carboxamide-HCl, when given at the dose of 10 mg/kg IP for 5 days prior to haloperidol (3 mg/kg IP 21 days) significantly prevented the up-regulation of striatal dopamine receptor supersensitivity, thus demonstrating a prophylactic effect. Two other analogues, L-prolyl-L-leucyl-5 aminomethyltetrazole and L-prolyl-L-leucyl-glycine-dimethylamide at a dose of 10 mg/kg IP when given concurrently with haloperidol for 21 days, suppressed the development of dopamine receptor supersensitivity. None of the analogues tested in the post-haloperidol session reversed the haloperidol-induced increase in the density of striatal dopamine receptors. Active PLG analogues hold promise as potential therapeutic agents for the amelioration of tardive dyskinesia. PMID- 2893361 TI - Mu-opiate binding and morphine antagonism by octapeptide analogs of somatostatin. AB - A series of cyclic conformationally restrained octapeptide analogs of somatostatin were examined for their ability to inhibit the binding of tritiated mu, kappa, and delta opiate receptor ligands. Several of these substances were found to have high affinity for mu opiate receptors while having very low affinity for both kappa and delta receptors. Previous suggestions that somatostatin analogs exhibit opiate antagonist activity led to a study of the ability of the two most potent compounds to inhibit morphine analgesia in rats after intracerebroventricular injection. One of the compounds significantly antagonized morphine analgesia although the other displayed severe toxicity. These two compounds differed in that the very toxic compound had previously been found to possess significant somatostatin activity. It thus appears that the structural requirements for toxicity and somatostatin activity can be differentiated from those for opiate activity. PMID- 2893362 TI - Tyr-MIF-1 and Met-enkephalin share a saturable blood-brain barrier transport system. AB - Previous studies have shown that methionine enkephalin and Tyr-MIF-1 are transported from the brain to the blood by a saturable, stereospecific, carrier mediated process. It was not established by these studies whether Tyr-MIF-1 and methionine enkephalin were transported by the same system or by separate, but overlapping systems. This issue was investigated in anesthetized mice receiving injections containing both 131I-methionine enkephalin and 125I-Tyr-MIF-1 into the lateral ventricle of the brain. Mice were decapitated and the brain to blood transport rate was derived from the residual counts in the brain. It was found that in individual mice, the transport rate for Tyr-MIF-1 correlated highly with the transport rate for methionine enkephalin but not with the transport of iodide. This shows that the transport of Tyr-MIF-1 is closely coupled to the transport of methionine enkephalin but dissociable from the brain to blood transport of iodide. Furthermore, the inability of varying doses of Tyr-MIF-1 or of methionine enkephalin to preferentially self-inhibit is radiolabeled form in comparison with the other peptide shows that, functionally, only a single system exists. Aluminum, a noncompetitive inhibitor of Tyr-MIF-1 transport, was also without preferential inhibition. Thus, under the conditions of these studies, only a single system could be functionally demonstrated for the transport of both Tyr-MIF-1 and methionine enkephalin. PMID- 2893363 TI - Somatostatin and its analog enhance the formation of human leukocyte migration inhibiting factor: further evidence for immunomodulatory action of somatostatin. AB - The effect of somatostatin-14 (SST) and somatostatin analog D-Phe-Cys-Phe-D-Trp Lys-Thr-Cys-Thr-NH2 (RC-102) on migration inhibition of human leukocytes induced by cardiac antigen or phytohemagglutinin (PHA) was investigated. Both SST and RC 102 augmented the migration inhibition, thus indicating the enhanced formation or action of the leukocyte migration inhibiting factor (LMIF). This finding provides additional evidence for the immunomodulatory action of somatostatin. PMID- 2893364 TI - [Neurological complications of anti-rabies vaccination with the Semple vaccine]. PMID- 2893365 TI - How to treat hypertension in diabetic patients. PMID- 2893366 TI - Amoebic peritonitis in pregnancy in the United Kingdom. AB - We describe a woman who developed hepatic amoebic abscesses during pregnancy, and subsequently amoebic peritonitis. We believe this to be the first such recorded case in the United Kingdom, and unusual in that the patient had never been abroad. PMID- 2893367 TI - Shaking behaviour induced by putrescine in naive rats: a pharmacological and histological study. AB - In untreated rats, the intraperitoneal injection of putrescine evoked a typical wet-dog shake response, that was maximal at a dose of 300 mg/kg and at room temperature (22 degrees) (number of shakes: 84.00 +/- 17.90/hr). In a hot environment (30 degrees) the number of shakes was markedly reduced (26.90 +/- 5.19/hr). The putrescine-induced shaking behaviour was unaffected by atropine, bicuculline, chlorpheniramine, cimetidine, methysergide, naloxone and noradrenaline, but was markedly antagonized by morphine. Naloxone pretreatment nullified the antagonistic activity of morphine. Histological studies showed marked alterations in brain vascular permeability, which was increased by putrescine. Morphine completely prevented this putrescine-induced vascular effect. These results suggest a correlation between WDS produced by putrescine and increase in brain vascular permeability. Furthermore they show that morphine can affect brain vascular permeability. PMID- 2893368 TI - Modes of determining beta-adrenoceptor number in human mononuclear leucocytes. AB - Inhibition of total 125I-ICYP binding to intact human mononuclear leucocytes at 32 degrees by propranolol and (+/-) CGP-12177 was biphasic. The high affinity component of 125I-ICYP binding, representing approximately 30% of total, was stereospecific, while the low affinity binding site was inhibited without stereospecificity. (-) Isoproterenol inhibited the high affinity component of 125I-ICYP binding only, with low affinity. By performing binding studies in intact cells at 4 degrees or in broken cell preparations at 37 degrees, the fraction of total 125I-ICYP binding representing specific binding was increased, and agonist affinity was high. Inhibition of 3H-CGP-12177 binding to intact cells at 32 degrees demonstrated a high fraction of specific binding and high agonist affinity. Computer-assisted analysis of total radioligand binding determined over a broad concentration range revealed two populations of saturable 125I-ICYP binding sites in intact cells as well as in broken cell preparations, while 3H CGP-12177 binding demonstrated only one saturable binding site. The number of high affinity 125I-ICYP binding sites was comparable to the number of saturable 3H-CGP-12177 binding sites. Receptor numbers determined by analysis of total radioligand binding were comparable to receptor numbers determined by subtraction of non-specific binding, determined in the presence of a high concentration of competing ligand. Analysis of total radioligand binding was found to be a better procedure because it eliminates the use of an arbitrary concentration of unlabelled ligand and improves the accuracy of the assay. PMID- 2893370 TI - [Traumatic tooth injuries. A clinical and experimental study]. PMID- 2893369 TI - [Mixed endocrine tumor of the pancreas (vipoma, glucagonoma). Treatment by somatostatin followed by one of its long-acting analogs]. AB - We describe the 4-year follow-up of an endocrine tumour of the pancreas (vipoma glucagonoma) treated with chemotherapy. To control the endocrine syndrome we used somatostatin 14 by continuous subcutaneous infusion for 1 year, followed by the somatostatin analogue SMS 201-995 administered alone without antitumoral chemotherapy. Under SMS 201-995 (100 micrograms 12-hourly) the endocrine syndrome dramatically improved. This effect persisted for 12 months after which a relative resistance to the drug developed. It was necessary to increase the dosage (300 400 micrograms/24 hours) and to alter the mode of administration (continuous subcutaneous infusion) to obtain a clinical benefit inferior to that obtained during the first year of treatment with SMS 201-995. At present this drug is given combined with recombinant interferon alpha 2A. In spite of computerized tomography, ultrasonography and monitoring of hormone levels we were unable to determine whether or not SMS 201-995 exerted a partial antitumoral effect. PMID- 2893371 TI - Traumatic tooth injuries. A clinical and experimental study. PMID- 2893372 TI - Distribution of glutamine synthetase and carbamoyl-phosphate synthetase I in vertebrate liver. AB - Mitochondrial glutamine synthetase (EC 6.3.1.2) is the primary ammonia detoxifying enzyme in avian liver and is therefore analogous in function to carbamoyl-phosphate synthetase I (ammonia) (EC 6.3.4.16) in mammalian liver. In mammalian liver, glutamine synthetase is cytosolic and its distribution is restricted to a few hepatocytes around the terminal venules. These cells do not express carbamoyl-phosphate synthetase I. Using immunocytochemistry, we show here that there is little or no zonation of glutamine synthetase in avian liver. Rather, it is broadly distributed to most hepatocytes, much like carbamoyl phosphate synthetase I in mammalian liver. In situ hybridization with a cloned glutamine synthetase cDNA probe showed the distribution of glutamine synthetase mRNA in both mammalian and avian liver to correspond to the distribution of immunoreactive protein. Neither glutamine synthetase nor carbamoyl-phosphate synthetase I and ornithine transcarbamoylase (EC 2.1.3.3) are strictly zoned in liver of the Texas tortoise or of an Argentine tree frog, both of which possess a complete urea cycle but which may also rely on glutamine synthetase for ammonia detoxication. These latter results suggest that the mutually exclusive expression of either carbamoyl-phosphate synthetase I or glutamine synthetase may be unique to mammalian liver. PMID- 2893373 TI - An extended HLA-D region haplotype associated with celiac disease. AB - Celiac disease has one of the strongest associations with HLA (human leukocyte antigen) class II markers of the known HLA-linked diseases. This association is primarily with the class II serologic specificities HLA-DR3 and -DQw2. We previously described a restriction fragment length polymorphism (RFLP) characterized by the presence of a 4.0-kilobase Rsa I fragment derived from an HLA class II beta-chain gene, which distinguishes the class II HLA haplotype of celiac disease patients from those of many serologically matched controls. We now report the isolation of this beta-chain gene from a bacteriophage genomic library constructed from the DNA of a celiac disease patient. Based on restriction mapping and differential hybridization with class II cDNA and oligonucleotide probes, this gene was identified as one encoding an HLA-DP beta chain. This celiac disease-associated HLA-DP beta-chain gene was flanked by HLA-DP alpha chain genes and, therefore, was probably in its normal chromosomal location. The HLA-DP alpha-chain genes of celiac disease patients also were studied by RFLP analysis; 84% of HLA-DR3, -DQw2 patients had a 16-kb Xba I fragment that was present in only 36% of HLA-DR3, -DQw2 controls. Moreover, 79% of these patients had both alpha- and beta-chain polymorphisms in contrast to 27% of controls. Thus, celiac disease is associated with a subset of HLA-DR3, -DQw2 haplotypes characterized by HLA-DP alpha- and beta-chain gene RFLPs. Within the celiac disease patient population, the joint segregation of these HLA-DP genes with those encoding the serologic specificities HLA-DR3 and -DQw2 indicates: (i) that the class II HLA haplotype associated with celiac disease is extended throughout the entire HLA-D region, and (ii) that celiac-disease susceptibility genes may reside as far centromeric on this haplotype as the HLA-DP subregion. PMID- 2893374 TI - MTrasT24, a metallothionein-ras fusion gene, modulates expression in cultured rat liver cells of two genes associated with in vivo liver cancer. AB - We studied the effects of a zinc-inducible metallothionein-ras fusion gene (MTrasT24) in cultured rat liver epithelial (RLE) cells on expression of two genes induced during liver carcinogenesis in vivo: gamma-glutamyltransferase [(5 glutamyl)-peptide:amino acid 5-glutamyltransferase, EC 2.3.2.2] and glutathione S transferase-P (RX:glutathione R-transferase, EC 2.5.1.18). Expression of MTrasT24 increased steady-state RNA levels of gamma-glutamyltransferase and glutathione transferase-P 6- to 100-fold and 1.6- to 6-fold, respectively; in contrast, levels of alpha-tubulin RNA fell slightly or were unchanged. RNA gel blots verified that gamma-glutamyltransferase and glutathione transferase-P RNAs were of the appropriate size, and results from immunocytochemistry on transfected cells demonstrated that RLE cells carrying MTrasT24 synthesized immunoreactive, appropriately localized gamma-glutamyltransferase and glutathione transferase-P. Zinc induction studies indicated that gamma-glutamyltransferase and glutathione transferase-P RNA levels were directly dependent on MTrasT24 RNA levels. These data suggest that expression of gamma-glutamyltransferase and glutathione transferase-P expression are part of a reorientation of cellular gene expression during carcinogenesis and that activated ras expression, like chemical carcinogens, can bring about this change. PMID- 2893375 TI - In situ hybridization histochemistry and immunocytochemistry reveal an increase in spinal dynorphin biosynthesis in a rat model of peripheral inflammation and hyperalgesia. AB - Dynorphin, an opioid peptide, is thought to play an important role in the modulation of nociceptive neural circuits at the level of the spinal cord. In a model of peripheral inflammation and hyperalgesia, an oligodeoxyribonucleotide probe complementary to a portion of preprodynorphin mRNA and antisera to dynorphin A-(1-8) were used to localize changes in dynorphin mRNA and peptide to individual spinal cord neurons. Intraplantar injection in rats of complete Freund's adjuvant resulted in edema and hyperalgesia to radiant heat stimulation of the injected hind paw that reached a peak at 4 days. At the same time, in situ hybridization histochemistry and immunocytochemistry identified an increase in transcription of preprodynorphin mRNA that was paralleled by an increase in dynorphin peptide. These changes were seen in spinal neurons in the medial two thirds of laminae I and II and in laminae V and VI of lumbar segments receiving innervation from the inflamed paw. Since neurons demonstrating the increase in dynorphin biosynthesis are located in both the superficial and deep dorsal horn laminae, our data provide evidence for opioid modulation of nociceptive neural circuits in these two distinct spinal locations. PMID- 2893376 TI - Autoradiographic localization of supraspinal kappa-opioid receptors with [125I Tyr1, D-Pro10]dynorphin A-(1-11). AB - [125I-Tyr1, D-Pro10]dynorphin A-(1-11) (125I-DP-DYN), an opioid peptide analogue that has previously been shown to be kappa selective, displays specific, saturable, and high-affinity (Kd = 0.3 nM) binding in slide-mounted sections from nerve tissue. We have used 125I-DPDYN to autoradiographically visualize supraspinal kappa-opioid receptor sites in rats, guinea pigs, and rabbits. The autoradiographic dispositions of 125I-DPDYN in sections from cerebellum are clearly different in guinea pig and rabbit, suggesting that kappa receptors have different functions in this organ of the two species. Autoradiograms from 125I DPDYN-labeled brain sections also reveal major species differences, in particular in thalamus, which is densely labeled in rabbit and considerably less so in rat and guinea pig. The data show that 125I-DPDYN is a useful probe to visualize kappa-opioid receptor sites in nerve tissue sections directly and rapidly. PMID- 2893377 TI - Number and continuous proliferative pattern of transplanted primitive immunohematopoietic stem cells. AB - We estimated numbers of transplantable primitive stem cells (PSCs) and found evidence that the same PSC continuously produced circulating erythrocytes and lymphocytes. These estimations used the binomial formula on data from recipients of identical portions of marrow mixtures containing two distinguishable cell types. Analysis of variance was used to compare repeated tests within each recipient. Values of pi s or pi c, probabilities that two independently sampled cells were descended from the same PSC, were also estimated, as this does not require the unverified condition that all PSCs contribute equally to the differentiated cell population. Several months after transplantation, erythrocytes were descended from only a single PSC per 1-2 X 10(5) marrow cells injected, several times rarer than previously reported. Percentages of erythrocyte and lymphocyte types in each recipient were closely correlated, with r values ranging from 0.86 to 0.94, in groups receiving 2-8 X 10(5) marrow cells; apparently the same precursors repopulated both myeloid and lymphoid lines in each recipient, as expected of true PSCs. Our data did not fit the clonal succession model, which predicts sequential activation of new PSCs and deactivation of old. Between 76 and 154 days, differentiated erythrocyte precursors were probably exhausted, with no evidence for new precursor activation or for further change between 154 and 250 days. The percentage of newly produced erythrocytes (reticulocytes) of each donor type varied little when individual recipients were followed between 165 and 295 days after transplantation, and variances within recipients were similar at marrow doses from 8 to 200 X 10(5) cells, further contradicting models of sequential activation and deactivation of PSC clones. Thus, transplanted PSCs were continually active during much of the recipient's lifespan. PMID- 2893378 TI - Receptors for prolactin, somatostatin, and luteinizing hormone-releasing hormone in experimental prostate cancer after treatment with analogs of luteinizing hormone-releasing hormone and somatostatin. AB - Membrane receptors for luteinizing hormone-releasing hormone (LH-RH), somatostatin, and prolactin (PRL) were investigated in the Dunning R-3327H rat prostate adenocarcinoma specimens after in vivo treatment with microcapsules of the agonist [D-Trp6]LH-RH and the somatostatin analog RC-160. The LH-RH receptors showed a low-binding affinity (Kd = 54 nM) and high capacity (Bmax = 12.0 pmol/mg). Treatment with the [D-Trp6]LH-RH decreased the binding affinity (Kd = 0.52 microM). Specific somatostatin receptors, with Kd = 1.3 nM and Bmax = 543 fmol/mg, were also found. Treatment with [D-Trp6]LH-RH lowered Bmax to 44 fmol/mg, and administration of RC-160 reduced Kd to 30 nM. After the combined treatment with the two analogs, Kd and Bmax were decreased. Specific PRL receptors (Kd = 0.72 nM; Bmax = 161 fmol/mg) were also detected. Treatment with either analog reduced Bmax by 50%, but a much greater reduction of PRL binding capacity was revealed after in vitro dissociation of the bound endogenous PRL by MgCl2. The dramatic fall in the total number of PRL receptors after combination treatment with both analogs could be partially responsible for the decrease in the weight and volume of prostate tumors. The findings support the concept that analogs of LH-RH and somatostatin can inhibit tumors directly through their own respective receptors. One of several mechanisms of the antineoplastic activity of these analogs could be the elimination of tumor growth-promoting effect of PRL by the reduction of the total number of PRL receptors. PMID- 2893381 TI - Fibronectin as a carrier for the transglutaminase from human erythrocytes. AB - Nondenaturing electrophoresis was used to demonstrate that, immediately upon exposure to plasma, the transglutaminase (protein-glutamine:amine gamma glutamyltransferase, EC 2.3.2.13) from erythrocytes undergoes a significant shift in mobility. The plasma effect shows saturable characteristics and depends entirely on the presence of fibronectin in plasma, indicative of complex formation between this protein and transglutaminase. The results suggest a specific carrier function for fibronectin that might be of physiological importance in determining the fate of a tissue transglutaminase accidentally discharged into plasma. PMID- 2893379 TI - Molecular cloning of amyloid cDNA derived from mRNA of the Alzheimer disease brain: coding and noncoding regions of the fetal precursor mRNA are expressed in the cortex. AB - To gain insight into factors associated with the excessive accumulation of beta amyloid in the Alzheimer disease (AD) brain, the present studies were initiated to distinguish between a unique primary structure of the AD-specific amyloid precursor mRNA vis a vis other determinants that may affect amyloid levels. Previous molecular cloning experiments focused on amyloid derived from sources other than AD cases. In the present work, we cloned and characterized amyloid cDNA derived directly from AD brain mRNA. Poly(A)+ RNA from AD cortices was used for the preparation of lambda gt11 recombinant cDNA libraries. An insert of 1564 nucleotides was isolated that included the beta-amyloid domain and corresponded to 75% of the coding region and approximately equal to 70% of the 3'-noncoding region of the fetal precursor amyloid cDNA reported by others. On RNA blots, the AD amyloid mRNA consisted of a doublet of 3.2 and 3.4 kilobases. In control and AD cases, the amyloid mRNA levels were nonuniform and were independent of glial specific mRNA levels. Based on the sequence analysis data, we conclude that a segment of the amyloid gene is expressed in the AD cortex as a high molecular weight precursor mRNA with major coding and 3'-noncoding regions that are identical to the fetal brain gene product. PMID- 2893380 TI - Synaptic transmission between rat cerebellar granule and Purkinje cells in dissociated cell culture: effects of excitatory-amino acid transmitter antagonists. AB - Monosynaptic excitatory connections between cerebellar granule and Purkinje cells were studied in dissociated cell cultures, and identification of the transmitter and the postsynaptic receptor at this synapse was pharmacologically investigated. The presynaptic granule cell and the postsynaptic Purkinje cell were voltage- or current-clamped simultaneously, and the excitatory postsynaptic current induced by the granule cell was examined. The neurons and monosynaptic excitatory connections were identified as in our earlier study. Several pairs of granule and Purkinje cells were stained with Lucifer yellow and propidium iodide, respectively, and their morphology was examined after electrophysiological recording. The monosynaptic excitatory postsynaptic current was suppressed by 1 mM kynurenate, an antagonist for excitatory-amino acid receptors, but was little affected by 0.2 mM DL-2-amino-5-phosphonovalerate, a selective antagonist of N methyl-D-aspartate receptors. Glutamate and aspartate induced inward current in the Purkinje cells. These currents were suppressed by kynurenate at 1 mM. DL-2 Amino-5-phosphonovalerate at 0.2 mM suppressed the inward current induced by 100 microM aspartate but did not affect the inward current induced by 10 microM glutamate. These results are consistent with the idea that glutamate, or a glutamate-like substance, but not aspartate is the transmitter released at the synapse between granule and Purkinje cells and that non-N-methyl-D-aspartate receptor channels are functioning in the postsynaptic membrane. PMID- 2893382 TI - Rod light adaptation may be mediated by acceleration of the phosphodiesterase guanylate cyclase cycle. AB - We compare the retinal rod photocurrent before and after introduction of an hydrolysis-resistant analog of GTP into the outer segment by the whole-cell patch technique. Others have shown that GTP bound to transducin leads to the hydrolysis of cyclic GMP, causing the response to light--a decrease in dark current. The hydrolysis-resistant GTP analog prolongs the response to a bright flash, which leads us to suggest that prolonged transducin activation by bright light desensitizes the rod by a prolonged decrease in dark current. Recovery from the response to a bright flash does occur after introduction of the analog; that recovery requires acceleration of cyclase activity rather than inhibition of phosphodiesterase. The analog mimics light adaptation by desensitizing the rod and speeding the recovery from a dim flash. The analog plus light or light adaptation prolongs the activities of transducin and phosphodiesterase (oligonucleate 5'-nucleotidohydrolase, EC 3.1.4.1) to mediate desensitization by reducing the dark current. Hence, this faster recovery from a dim flash would be by increased activity of guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] rather than by inhibited phosphodiesterase. Accelerated activity of guanylate cyclase may speed recovery by response truncation. We conclude that transducin, activated by photolyzed rhodopsin, may lead to increased activity of both phosphodiesterase and guanylate cyclase to mediate the desensitization and the faster recovery of the light-adapted response. PMID- 2893383 TI - Nutrition and platelet function in atherogenesis. PMID- 2893384 TI - DNA markers for the cystic fibrosis locus. PMID- 2893385 TI - The application of molecular genetics to the study of the basic defect causing cystic fibrosis. AB - The first linkage to CF was demonstrated to the enzyme paroxonase, a classical protein polymorphism, by the Copenhagen group. This was followed quickly by six cloned DNA sequences: pJ3.11, 7C22, COL1A2 and TCRB (St. Mary's), 917 (Toronto) and met (Salt Lake City). Both pJ3.11 and met are very close genetically to the CF mutation, and can be used for carrier detection and antenatal diagnosis in many informative families where there is a CF child. There is no evidence for heterogeneity of the CF locus. The collection of markers surrounding the CF locus is now sufficient to permit attempts to be made to isolate the defective gene using a combination of chromosome-mediated gene transfer, pulse field gel electrophoresis, NotI junction libraries, cosmid mapping and chromosome walking techniques. PMID- 2893386 TI - Molecular approaches to the cystic fibrosis gene. PMID- 2893387 TI - A genotype-dependent hippocampal dynorphinergic mechanism controls mouse exploration. AB - Following microinjections with two dilutions of anti-dynorphin B antiserum into the hippocampal CA3 region, adult male mice from the inbred strains DBA/2 and C57BL/6 were individually tested for various exploratory behaviors in a novel environment and compared to preimmune serum control animals. Treatment augmented vertically-oriented exploratory acts in strain DBA/2 and reduced the scores in strain C57BL/6 so that strain differences originally present between the controls were reversed or eliminated after antiserum. These opposite effects indicate that a hippocampal dynorphinergic mechanism is involved in the regulation of novelty induced behavior in mice and that its modulatory function depends on the genotype. It is concluded that DBA/2 animals exposed to novelty, as compared to C57BL/6, are characterized by an over-release of hippocampal dynorphin B which is neutralized in part by small amounts of antibody. PMID- 2893388 TI - D1 and D2 dopamine binding site up-regulation and apomorphine-induced stereotypy. AB - Treatments with drugs to up-regulate specific receptors is a strategy often employed in mechanism of action studies. In this type of experiment, changes in the numbers of receptors and concomitant changes in an animal's sensitivity to the drug have been used as evidence for the participation of the binding site in the behavior. In these studies, to test for the role of D1 and D2 receptors in apomorphine-induced stereotypy (AIS), dopamine binding sites were up-regulated by appropriate pre-treatments and the ability of these pre-treatments to alter AIS was subsequently investigated. In the first experiment, 19 days of pre-treatment with SCH 23390 or haloperidol selectively increased by 35 and 40% the numbers of striatal D1 and D2 binding sites, respectively, without affecting their affinities. However, when challenged with apomorphine, only the animals pre treated with the D2 antagonist showed behavioral supersensitivity. In the second experiment, reserpine pre-treatment (30 mg/kg IP, 24-hr pre-test) increased the numbers of D1 binding sites by 18%, but did not significantly alter the numbers of striatal D2 binding sites. Behaviorally, these rats were supersensitive to apomorphine's stereotypy-inducing effects; however, they also showed an increased sensitivity to the ability of either haloperidol or SCH 23390 to block AIS. Moreover, this blockade was only attenuated by a D2 (but not a D1) agonist. Collectively, these data suggest that AIS is mediated by both D1 and D2 binding sites, but that D2 binding sites have a more important role. PMID- 2893390 TI - Tyr-MIF-1 augments benzodiazepine receptor binding in vivo. AB - Behavioral and limited neurochemical evidence indicates possible links between the endogenous opiate and gamma-aminobutyric acid (GABA)-benzodiazepine receptor systems. A previous study using in vitro techniques indicated that MIF-1 (Pro-Leu Gly-NH2) and Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), peptides with anti-opiate activity, enhanced GABA-stimulated benzodiazepine binding. To assess the activity of these peptides under in vivo conditions, we evaluated their effects on benzodiazepine receptor binding as determined by specific uptake of the benzodiazepine antagonist [3H]-Ro15-1788. Tyr-MIF-1, at a dose of 1 mg/kg IP, significantly augmented benzodiazepine binding in cortex and hippocampus but not in cerebellum, hypothalamus, or pons-medulla. Increases in binding were due in large part to increased apparent affinity at the receptor. At none of the doses of MIF-1 (0.1, 1 and 10 mg/kg) or at the highest (10 mg/kg) and lowest (0.1 mg/kg) doses of Tyr MIF-1 was there any significant alteration in benzodiazepine binding in any region evaluated. These results indicate that peptide-benzodiazepine receptor interactions may also occur in vivo. PMID- 2893389 TI - Different effects of ethylketocyclazocine on phencyclidine- and N allylnormetazocine-induced stereotyped behaviors in rats. AB - The effects of ethylketocyclazocine (EKC) on the stereotyped behaviors induced by intraperitoneal injection of phencyclidine (PCP) or N-allylnormetazocine (SKF 10,047) were examined. EKC markedly antagonized PCP-induced stereotyped behaviors such as sniffing, head-weaving, turning and backpedalling. On the other hand, EKC failed to antagonize SKF 10,047-induced stereotyped behaviors, which are PCP-like stereotyped behaviors, except sniffing and head-weaving at 0-15 min after the SKF 10,047 injection. PCP-induced turning and backpedalling were potentiated by pretreatment with SKF 10,047, while PCP-induced sniffing and head-weaving were not. EKC failed to affect the enhancing effect of SKF 10,047 on PCP-induced turning and backpedalling. These results suggest that part of the PCP- and SKF 10,047-induced stereotypy may be mediated by different neuronal mechanisms. PMID- 2893391 TI - Preliminary evaluation of manassantin A, a potential neuroleptic agent from Saururus cernuus. AB - Manassantin A (MNS-A), a novel dineolignan isolated from Saururus cernuus was evaluated for its central depressant effects. Intraperitoneal (IP) administration of MNS-A to mice at nontoxic doses caused a decrease in spontaneous motor activity and inhibition of amphetamine-induced stereotypy, with an ED50 of 0.21 +/- 0.02 mg/kg for its antiamphetamine activity. Doses of MNS-A up to the LD50 did not produce catalepsy and ptosis as were observed with haloperidol used as a reference drug. The compound caused a dose-dependent hypothermia, while haloperidol was not very effective in this test. Potentiation of pentobarbital sleeping time was observed to be of comparable degree with both drugs. In spite of the higher toxicity (acute LD50 5.4 +/- 0.2 mg/kg, IP) than that shown by haloperidol, the somewhat selective neuroleptic profile of MNS-A makes it an interesting candidate for more detailed studies. PMID- 2893392 TI - Abuse liability of benzodiazepines. PMID- 2893393 TI - Comparison of the renal and pulmonary hemodynamic effects of fenoldopam, dobutamine, dopamine and norepinephrine in the anesthetized dog. AB - The renal and pulmonary hemodynamic effects of fenoldopam, dobutamine, dopamine and norepinephrine were compared in the pentobarbital-anesthetized dog. Animals were pretreated with propranolol (1 mg/kg, i.v.) to eliminate beta-adrenoceptor mediated effects in the renal and pulmonary circulations. Heparinized blood was withdrawn from the right femoral artery and transferred, via a peristaltic pump, to the pulmonary arterial branch supplying the left diaphragmatic lobe of the lung. The flow rate of the pump was set so that the perfusion pressure in the lobe was equal to resting diastolic pulmonary artery blood pressure. Under these conditions of constant flow, changes in perfusion pressure reflect changes in pulmonary vascular resistance. Renal blood flow was measured in the same experiments via an electromagnetic flow probe which was placed directly on the left renal artery. Intraarterial administration of fenoldopam resulted in a marked reduction in renal vascular resistance at doses that had virtually no effect on pulmonary vascular resistance. Conversely, dobutamine increased pulmonary vascular resistance slightly, and had no effect on the renal circulation. Dopamine increased pulmonary vascular resistance at all doses, and exhibited a biphasic effect on renal vascular resistance. At low doses, dopamine produced a modest reduction in renal vascular resistance, and at higher doses, dopamine significantly increased renal vascular resistance. Norepinephrine increased both pulmonary and renal vascular resistance at all doses, as expected. These results indicate that fenoldopam may be hemodynamically favorable over dobutamine and dopamine in the management of patients with low output cardiac failure since fenoldopam improves renal hemodynamics at doses that have little or no effect on the pulmonary circulation. PMID- 2893394 TI - Effect of esmolol on the ventricular fibrillation threshold. AB - The effect of esmolol on the ventricular fibrillation threshold (VFT) was determined in 11 open-chest dogs anesthetized with sodium pentobarbital. Since changes in VFT by antiarrhythmic drugs have been shown to depend on the method used to test vulnerability to fibrillation, two methods were studied. The vulnerable period was scanned with a train of pulses (100 Hz, 4 ms, 20 pulses) in nine experiments and a single pulse (10 ms) in eight experiments. Following control measurements, esmolol was administered as an intravenous bolus of 500 micrograms/kg followed by a continuous infusion of 300 micrograms/kg/min. After 15 min of infusion, the adequacy of beta-blockade was tested by the administration of 0.5 micrograms/kg of isoproterenol. Isoproterenol increased the heart rate by only 18 +/- 2 beats/min following esmolol administration which was significantly less than the control response (79 +/- 7 beats/min, p less than 0.01). Although the VFT measured with the single-pulse technique did not change in response to esmolol (14.1 +/- 1.1 mA vs. 14.3 +/- 1.2 mA), the VFT measured with the train-of-pulses technique significantly increased (3.7 +/- 0.5 mA to 14.5 +/- 2.8 mA, p less than 0.01). Twenty minutes after discontinuing esmolol, the VFT measurements were repeated and did not differ from control values with either technique. The increase in heart rate in response to isoproterenol also returned to control values (80 +/- 6 beats/min). The results suggest that the ability of esmolol to raise VFT as measured by the train-of-pulses technique is due to beta-adrenergic blockade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893395 TI - Behavioral pharmacology of minor tranquilizers. PMID- 2893396 TI - On the distribution of REM and NREM sleep under two benzodiazepines with comparable receptor affinity but different kinetic properties. AB - Two clinical-pharmacological investigations were performed to give a retrospective and explorative record, based on electroencephalographic parameters, of spindle density and REM distribution in the first and second halves of the night under a short-acting (triazolam) and medium-acting (lormetazepam) benzodiazepine. A further aim was to determine whether a suitable dose of a short-acting benzodiazepine could lead to a REM suppression in the first sleep cycles and a REM compensation in later sleep cycles on the same night. Since sleep spindles are increased and rapid eye movements reduced under benzodiazepines, the two phenomena were respectively taken as indicators of drug effects on NREM and REM sleep. According to the receptor affinity of the two substances, dosages of triazolam and lormetazepam ought to be equieffective in a ratio of about 1:2. Yet clinical experience has shown that a ratio of 1:4 (0.5 mg triazolam vs. 2 mg lormetazepam) gives the doses that are equieffective and which are widely used in clinical practice. The changes in the number of sleep spindles and rapid eye movements documented the different kinetic properties of the two substances. Even after clinically equieffective doses, the changes in the parameters were less marked under lormetazepam than under triazolam. This suggests that the two benzodiazepines different effects on spindle and REM distribution were not attributable to their kinetics, but that pharmacodynamic aspects must also be considered, even if this does not fit in with the prevalent picture of the benzodiazepines mechanisms of action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893397 TI - Neuronal transmitter sensitivity after social isolation in rats. AB - After 3 and 12 months of isolation rearing of rats, sensitivity of single neurons to microiontophoretically applied transmitters as well as neuronal spontaneous activity are analysed in striatum, cortex, hippocampus, locus coeruleus and nucleus raphis medialis. It is demonstrated that regulation of transmitter sensitivity, as well as spontaneous activity, depend on isolation duration, therefore showing time dynamics. Sensitivity changes of single neurons to distinct transmitters are not uniform and simultaneous in all areas but are structure specific. After 3 months of isolation an enhanced dopamine sensitivity is observed only in the striatum, whereas in the cortex the dopamine sensitivity is increased after 12 months isolation. A diminished response of single neuron activity to serotonin is demonstrable after 3 months of isolation in striatum and nucleus raphis. The observed changes are discussed in connection with biochemically and pharmacologically demonstrated changes in isolation. The complex patterns of neurobiological changes characterizing the isolation syndrome are emphasized. PMID- 2893398 TI - Pharmacology of the pyrazolo-type compounds: agonist, antagonist and inverse agonist actions. AB - Five compounds that bind to the benzodiazepine (BZ) receptor, but show different pharmacological characteristics from the classical BZs, are profiled. CGS 8216 is a BZ antagonist/inverse agonist that reverses the effects of diazepam and also acts as a proconvulsant. CGS 9895 is also a potent BZ antagonist. In addition, this compound shows an anxiolytic profile. CGS 9896, CGS 17867A and CGS 20625 are BZ agonists (i.e., anxiolytics and anticonvulsants) which produce varying magnitudes of antagonist effect. All of these compounds are unique from the classical BZs in that each has a reduced propensity to produce the sedative and/or muscle relaxant effects characteristically associated with BZs. PMID- 2893400 TI - [Our nurses report from Havana]. PMID- 2893399 TI - Neurochemical correlates of male sexual behavior. AB - This report presents evidence of changes in the concentration of monoamine neurotransmitters and their metabolites in homogenates of spinal cord and brain areas of male rats related to specific events of their mating behavior. Intact male rats were allowed to copulate with receptive females and decapitated immediately after either the first intromission or the first ejaculation. Non mating control animals were exposed to other males, instead of females. The concentration of monoamines (norepinephrine, dopamine and serotonin) and some of their major metabolites (DOPAC and HIAA) in homogenates of discrete brain areas (parietal cortex, preoptic region, mediobasal hypothalamus) and lumbosacral spinal cord were measured by HPLC-ED. Results suggest that sexual arousal is associated with both increased dopaminergic activity in the preoptic region and inhibition of descending monoaminergic signals to the lumbosacral cord, whereas ejaculation is accompanied by increased activity of the serotonergic, as well as dopaminergic, innervation of the preoptic region. These findings give neurochemical support to notions of central monoamines involvement in sexual behavior suggested by previous pharmacological studies. PMID- 2893401 TI - Rational use of sedative/hypnotics. AB - Among medications targeted at the central nervous system, sedative/hypnotics are the most widely prescribed. The use of sedative/hypnotics is reviewed in the context of historical influences on prescribing practice and from a current neuroscience perspective. Recommendations are made regarding appropriate applications for these drugs, and the principles for choosing one drug over another are emphasized. PMID- 2893402 TI - [Neurochemical knowledge in electroconvulsive therapy (ECT)]. AB - The paper is concerned with an attempt to generalize and categorize current hypotheses on the biochemical basis of ECT. The hypotheses are critically evaluated with respect to the relevance of their experimental fundamentals. Thus, certain hypotheses are valid only in a qualified sense. Particular interest is focussed on those conceptions which try to correlate ECT-induced changes in synaptic receptor sensitivities (up-/down-regulation) with super- resp. subsensitivity hypotheses of psychoses. In this connection, noradrenergic and opioid systems on the one hand, and the axis hypothalamus-hypophysis on the other hand seem to play a dominant role. PMID- 2893403 TI - Comparative study of schizophrenic patients relapsed on and off medication. AB - The frequency of stressful life events, the characteristic psychopathological features, and the course of relapse were studied in 22 schizophrenic patients who relapsed while on maintenance neuroleptic medication and 27 noncompliant patients off treatment. The patients who relapsed while on neuroleptics experienced more independent life events, mainly losses and family conflicts, in the months preceding admission. Patients who relapsed while not on drugs were characterized by a more severe psychopathological picture dominated by positive symptoms at admission. Schizophrenic patients who relapsed on medication showed greater improvement and required shorter hospitalization. PMID- 2893404 TI - Neurotransmitter amino acids in post-mortem brains of chronic schizophrenic patients. AB - Neurotransmitter amino acids were measured in post-mortem caudate nucleus, nucleus accumbens, frontal cortex, amygdala, and hypothalamus of chronic schizophrenic and normal control subjects. The concentrations of upsilon aminobutyric acid (GABA), taurine, glycine-threonine, glutamate, aspartate, glutamine, tryptophan, and alanine were similar in both groups, with the exception of decreased GABA and tryptophan in the amygdala of the schizophrenic group. Strong positive correlations were obtained between the concentration of tryptophan, a putative agonal status marker of post-mortem brain tissue, and the concentration of GABA in all brain areas. When the GABA concentrations were adjusted for tryptophan concentrations in amygdala, the difference between the schizophrenic and control samples was no longer significant, suggesting that the original difference may have been due to different agonal or post-mortem changes in the tissues. There were, however, no significant correlations between GABA and post-mortem interval. The present results do not support the aminoacidergic hypotheses of chronic schizophrenia, although a GABA deficiency cannot be entirely excluded. PMID- 2893405 TI - Lateralized neuroleptic-induced side effects are associated with asymmetric visual evoked potentials. AB - Recent studies suggest that neuroleptic drugs may have an asymmetric effect on the two cerebral hemispheres. This effect is reflected by emergence of drug induced lateralized extrapyramidal side effects and by dose-related alterations in electrophysiological asymmetries. The present study examined the hypothesis that asymmetry of visual evoked potentials (VEPs) is associated with lateralized appearance of neuroleptic-induced parkinsonism or tardive dyskinesia (TD). The asymmetry of the amplitudes of later VEP components was significantly higher in patients with lateralized side effects (n = 8) than in patients with symmetrical side effects (n = 6) or free of extrapyramidal side effects (n = 11). The possibility that VEP asymmetry reflects the differential degree to which the two hemispheres are affected by medication is discussed. PMID- 2893406 TI - Enlargement of cerebrospinal fluid spaces in long-term benzodiazepine abusers. AB - In 17 benzodiazepine (BDZ) dependent in-patients a CT scan was performed before initiation of withdrawal therapy. The evaluation of the ventricular to brain ratio (VBR) by standardized and computerized measurements revealed significantly higher mean VBRs for both high- and low-dose BDZ-dependent patients compared to the mean VBR of an age- and sex-matched control group. In addition, the mean VBR of high-dose BDZ-dependent patients (N = 8) was significantly higher than the mean VBR of low-dose BDZ-dependent patients (N = 9). This difference could not be accounted for by the age of the patients or duration of BDZ-dependency and, therefore, suggests a dose-dependent effect of BDZs on the enlargement of internal CSF-spaces. On the other hand, higher values for the width of external CSF-spaces were found to be related to increasing age of the patients and duration of BDZ-dependency. PMID- 2893407 TI - Neuroleptic effects on platelet aggregation: a study in normal volunteers and schizophrenics. AB - Platelet-rich plasma from healthy controls was pre-treated with neuroleptics of the phenothiazine, butyrophenone or benzamide variety before aggregation with one of the following agonist agents: ADP, adrenaline, 5-HT, collagen, platelet activating factor or ristocetin. All compounds effective as antipsychotics, except sulpiride, depressed aggregation. Unmedicated schizophrenics showed aggregation responses indistinguishable from healthy controls. However, within days of treatment with either trifluoroperazine or haloperidol responses became abnormal in acutely psychotic patients. Increased responses to 5-HT and depressed responses to platelet activating factor were detected. After 4 weeks of treatment responses tended to return to normal. Aggregation responses were normal in those patients on long-term depot neuroleptics. PMID- 2893408 TI - Psychotropic drug utilization and audit in two Italian psychiatric services. AB - The utilization of psychotropic drugs is a topic of increasing interest. This paper describes a study of psychotropic drug use in two acute psychiatric in patient services in Cremona, northern Italy. Almost all patients surveyed received one or more psychotropic drugs, and there was evidence of a substantial level of polypharmacy. Women patients were prescribed more psychotropic drugs than the men, while the relationship between drug prescription and psychiatric diagnosis differed between the two services. During the second phase of the study, the medical staff were aware that their prescribing was being monitored. However, this knowledge appeared to have little effect on their patterns of prescribing. The findings of Barton (1978) are thus not supported. PMID- 2893409 TI - The effects of chronic intermittent stress on basal and acute stress levels of TSH and GH, and their response to hypothalamic regulatory factors in the rat. AB - The effect of chronic stress on basal and stress-induced alterations of TSH and GH was studied in adult male rats. Chronically stressed rats were subjected 6 days per week for 4 weeks to several acute stressors including saline injections, noise, ether and forced swimming. Each day, one stressor was chosen randomly. Twenty hr after the last stress session, basal levels of TSH were normal or increased, with no altered pituitary response to TRH. In contrast, the TSH rise induced by acute stress was blunted in chronically stressed rats. Chronic stress resulted in lower basal and acute stress levels of GH. These modifications were probably due to changes in the release of hypothalamic regulatory hormones, because no evidence for altered TSH response to TRH, and GH response either to GHRH or to somatostatin, was found. Some abnormal responses of GH to TRH and of TSH to GHRH were observed in chronically stressed rats. These data indicate that this type of chronic stress induced significant changes in basal and acute stress levels of GH and TSH in the rat. PMID- 2893410 TI - Suriclone and diazepam in the treatment of neurotic anxiety. A double-blind cross over trial. AB - Suriclone is a new anxiolytic drug belonging to the family of cyclopyrrolones. Although chemically entirely different from the benzodiazepines, it acts as a benzodiazepine agonist with very high affinity for the benzodiazepine receptors. In the present cross-over study, 33 out-patients with a diagnosis of neurotic anxiety were treated with suriclone (mean dose 2 mg/day) and diazepam (25 mg/day) in two 6-week periods. Both drugs had a significant anxiolytic effect, but diazepam appeared to have a better effect within the first 2 weeks of treatment, while no significant difference was seen after treatment, while no significant difference was seen after treatment for 6 weeks. Suriclone and diazepam had a different side effect profile: suriclone produced mainly dizziness, while diazepam caused sedation. This may reflect the fact that suriclone and benzodiazepines bind to distinct sites or different allosteric conformations of the benzodiazepine receptors. PMID- 2893411 TI - The paw test: a behavioural paradigm for differentiating between classical and atypical neuroleptic drugs. AB - An often used animal model based on the effects of neuroleptics on spontaneous behaviour is the catalepsy test. However, this test seems to be particularly insensitive to the atypical neuroleptics thioridazine and, especially, clozapine. We have therefore developed an alternative test, the paw test, which measures the ability of drugs to prevent the spontaneous withdrawal of fore- and hindlimbs in rats, and have compared this with the classical catalepsy test. The results show that: 1) the classical neuroleptic drugs haloperidol and chlorpromazine, the atypical neuroleptic drugs clozapine and thioridazine, the potential atypical neuroleptic drugs molindone and SCH 23390, and the potential classical neuroleptic drug metoclopramide are potent in increasing the hindlimb retraction time; 2) the paw test discriminates between classical neuroleptics which are equipotent in prolonging both the forelimb (FRT) and hindlimb retraction time (HRT) an atypical neuroleptics which are much more potent in prolonging HRT than in prolonging FRT; 3) the non-neuroleptic drugs desipramine, diazepam and morphine do not influence the variables measured in the paw test, although morphine does produce catalepsy; 4) Molindone as well as SCH 23390 behave like atypical neuroleptic drugs in the paw test. In comparison with the classical wood block catalepsy test, the paw test is shown to be superior for predicting the profile of the neuroleptics tested. Although more neuroleptics and non neuroleptics have to be tested to determine whether false positives and false negatives do occur, we feel that the paw test might be an interesting animal model, because the increase in hindlimb retraction time was associated with the antipsychotic potential, whereas the increase in forelimb retraction time was associated with the potential to induce so-called extrapyramidal side effects. PMID- 2893413 TI - Time-response curves of homovanillic acid in caudate and pre-frontal cortex following acute neuroleptic administration. PMID- 2893412 TI - Effects of the novel anxiolytics gepirone, buspirone and ipsapirone on free feeding and on feeding induced by 8-OH-DPAT. AB - The effects of the novel anxiolytics gepirone, buspirone and ipsapirone on free feeding and on feeding induced by the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n propylamino) tetralin (8-OH-DPAT), were examined. Gepirone dose-dependently increased feeding 2 and 4 h after injection, the magnitude of the response being larger than previously observed with any other 5-HT1A receptor ligand. Previous studies have suggested that buspirone and ipsapirone can block some of the behavioural effects of 8-OH-DPAT. However, gepirone, buspirone and ipsapirone did not inhibit feeding induced by 8-OH-DPAT. These results indicate that gepirone is a very efficacious appetite stimulant in rats and suggest that gepirone, buspirone and ipsapirone act as 5-HT autoreceptor agonists in the feeding model. PMID- 2893414 TI - Phencyclidine (PCP)-like discriminative stimulus effects of metaphit and of 2 amino-5-phosphonovalerate in pigeons: generality across different training doses of PCP. AB - Pigeons were trained to discriminate either a fixed dose of PCP (1 mg/kg; n = 3) or a progressively decreasing dose (1-0.56-0.32 mg/kg; n = 4) from saline. Lowering of the training dose shifted the dose-effect curve for PCP's discriminative stimulus effects about 5-fold to the left, in a parallel manner, but did not decrease the accuracy of the discrimination performance and did not significantly increase the extent to which pentobarbital and chlordiazepoxide produced PCP-appropriate responding. Dose-effect curves based on binary generalization data were evaluated statistically with new methods that may be more appropriate than those used previously. Metaphit, a proposed PCP-receptor acylator, and 2-amino-5-phosphonovalerate (AP5), an N-methyl-D-aspartate (NMDA) antagonist, produced complete PCP-appropriate responding in the high training dose group only at doses that suppressed the rate of responding and that produced ataxia. However, 4-fold lower doses of metaphit and AP5, which did not produce directly observable behavioral effects, were found to substitute completely for PCP in the low training dose group. These data support the notion that PCP, metaphit, and AP5 have a common discriminative effect in pigeons. PMID- 2893416 TI - Effects of pyrazolopyridines and a triazolopyridazine on the pentobarbital discriminative stimulus. AB - Rats were trained to discriminate injections of racemic pentobarbital (5.0 mg/kg) from saline in a two-lever drug discrimination task. After stable discrimination performance was attained, stimulus generalization studies were conducted with another barbiturate (barbital), benzodiazepine derivatives (diazepam and chlordiazepoxide), pyrazolopyridine derivatives (etazolate, cartazolate, and tracazolate), and a triazolopyridazine (CL 218, 872). The pentobarbital stimulus generalized to all of these compounds, except cartazolate. In addition, the administration of the benzodiazepine receptor antagonist flumazepil prior to benzodiazepine or triazolopyridazine administration produced a dose-related antagonism of each generalization. In contrast, the administration of flumazepil before barbiturate or pyrazolopyridine (i.e., etazolate or tracazolate) injection resulted in no attenuation of these generalizations. The results indicate that while certain barbiturates, benzodiazepines, pyrazolopyridines and triazolopyridazines are capable of producing similar stimulus effects, the behavioral actions of these agents can be differentiated on the basis of their susceptibility to antagonism by flumazepil. PMID- 2893415 TI - Antagonism by cholinomimetic drugs of the turning induced by intrastriatal pirenzepine in mice. AB - In order to investigate the behavioural effect of selective blockade of M1 muscarinic receptors in the forebrain, and to characterize a new model for the evaluation of muscarinic agonistic activity, the effect of intrastriatally injected pirenzepine was studied in mice. The direct injection of pirenzepine (0.01-1 microgram/mouse) into the right striatum of conscious mice resulted in contralateral turning behaviour. When injected intraperitoneally (IP) 15 min before pirenzepine (1 microgram), the muscarinic receptor agonists arecoline and pilocarpine (0.3-3 mg/kg), oxotremorine (0.003-0.03 mg/kg) and RS 86 (0.03-1 mg/kg) antagonized pirenzepine-induced turning, as did the choline-esterase inhibitor physostigmine (0.01-0.1 mg/kg) and the nootropic drug aniracetam (10-30 mg/kg). Haloperidol (0.03-0.3 mg/kg IP) weakly, but significantly, decreased the effect of pirenzepine, whereas (+/-) sulpiride (3-100 mg/kg) failed to affect it. Finally, (+/-)-amphetamine (0.1-3 mg/kg IP), citalopram (1-30 mg/kg IP) and muscimol (0.03-0.3 mg/kg IP) failed to modify pirenzepine-induced turning when administered prior to intrastriatal pirenzepine. These results suggest an involvement of M1 muscarinic receptors in rotational behaviour, and indicate that pirenzepine-induced turning may represent a new model for studying the central activity of cholinomimetic drugs. PMID- 2893418 TI - Stimulus properties of benzodiazepines: correlations with binding affinities, therapeutic potency, and structure activity relationships (SAR). AB - Using a two-lever operant choice task, rats were trained to discriminate diazepam (3.0 mg/kg) from saline under a fixed-ratio 10 (FR10) schedule of reinforcement. Once the discrimination was learned, generalization studies were conducted using various doses of 17 benzodiazepine derivatives. The diazepam stimulus generalized in a dose-related manner to each of these compounds. ED50 values were compared with available data on displacing affinities (Ki values) for tritiated diazepam brain binding in man, and with human therapeutic potency. A significant correlation (r = 0.88, n = 9) was found between benzodiazepine binding affinities and ED50 values derived from the diazepam stimulus generalization assay. A significant correlation (r = 0.92, n = 10) was also found between drug discrimination ED50 values and human therapeutic potencies. Finally, the benzodiazepine structure activity relationships generated from the drug discrimination studies closely paralleled the known structure activity relationships for these agents. The results provide further evidence that benzodiazepines exert their pharmacological effects through an interaction with benzodiazepine receptors. PMID- 2893417 TI - Amnestic effects of lormetazepam and their reversal by the benzodiazepine antagonist Ro 15-1788. AB - A combined visual (pictures) and auditory (word lists) memory test developed to trace the course of information processing under pharmacological or other influences was validated in a group of 20 subjects (control group) and then applied to determine the amnesic effects of lormetazepam and the reversal of these effects by the benzodiazepine antagonist Ro 15-1788. Three groups of n = 10 subjects received either 0.02 mg/kg IV lormetazepam (groups B and C) or placebo (group A) followed 14 min later by 0.03 mg/kg IV Ro 15-1788 (groups A and C) or placebo (group B). The time course of memory performance in the three groups was investigated and compared across three consecutive 14-min phases: before (phase 1) and after (phase 2) the first intravenous administration, and after the second treatment (phase 3). Results were also compared with those of 20 subjects from a drug-free control group in order to verify the memory test. Lormetazepam clearly impaired immediate and delayed free recall as well as recognition in both visual and auditory tasks. These effects were completely reversed by Ro 15-1788, which alone had no clear effect on memory performance in this study. Psychometric scales indicated concomitant sedation and impaired concentration after lormetazepam alone. Interestingly, lormetazepam retrogradely enhanced performance in the visual test of delayed free recall. The impaired acquisition of new information after the administration of lormetazepam may be associated with an improvement of the consolidation process of information acquired before drug treatment. PMID- 2893420 TI - Behavioral and neurochemical characteristics of stimulant-induced augmentation. PMID- 2893419 TI - Postsynaptic dopamine (DA) receptor stimulator properties of the putative DA autoreceptor-selective agonist B-HT 920 uncovered by co-treatment with the D-1 agonist SK&F 38393. AB - Postsynaptic dopaminergic behavioural effects of D-2 agonists can be promoted by concomitant D-1 receptor activation. The present experiment explored whether such effects could be elicited by the putative autoreceptor-selective D-2 agonist B-HT 920, when combined with the D-1 agonist SK&F 38393. Except for occasional jerks induced by B-HT 920, neither agonist caused significant dopaminergic stimulation when given separately, whereas combined treatment with SK&F 38393 and B-HT 920 induced clear-cut motor activation--particularly focused stereotyped licking and sniffing--in reserpine/AMT-pretreated rats. Both the D-1 antagonist SCH 23390 and the D-2 antagonist spiperone abolished these effects, while the SK&F/B-HT-induced stimulation was not significantly affected by the alpha 2-blocker idazoxan. It appears that classical postsynaptic DA receptor-stimulatory properties of B-HT 920 can indeed be demonstrated, provided that sufficient D-1 receptor tone prevails. PMID- 2893421 TI - A single injection of diazepam induces long-lasting sensitization. PMID- 2893423 TI - Ethanol stimulates GABA receptor-mediated Cl- ion flux in vitro: possible relationship to the anxiolytic and intoxicating actions of alcohol. PMID- 2893422 TI - Alerting drugs: do they really work? PMID- 2893424 TI - Teratogenicity of psychotherapeutic medications. PMID- 2893426 TI - Cognitive impairment due to AIDS-related complex and its response to psychostimulants. PMID- 2893425 TI - Pharmacologic treatment of eating disorders. Review of selected literature and recommendations. PMID- 2893427 TI - [Specificity against group A, C, and G streptococci of the reverse CAMP test for identifying Clostridium perfringens]. AB - We studied "reverse CAMP" test specificity for the identification of Clostridium perfringens, and the probable existence of cross-reactions with groups A, C and G streptococci. Ninety eight Clostridium strains were tested with ten S. agalactiae, ten S. pyogenes, two group C streptococci and one group G. All the strains of S. agalactiae yielded a positive "reverse CAMP" reaction when it was performed with C. perfringens strains. Cross-reactions were not detected when C. perfringens were tested with groups A, C or G streptococci. The "reverse CAMP" test proved to be specific for all the C. perfringens strains used. PMID- 2893428 TI - [Virus and abnormality of immuno-system]. PMID- 2893429 TI - [Genetical defects in immunodeficiencies]. PMID- 2893430 TI - Phencyclidine and the dissociatives. PMID- 2893431 TI - Brain mechanisms of drug reward and euphoria. AB - Drugs of abuse have in common the fact that they serve as biological rewards. They presumably do so because of their ability to activate endogenous brain circuitry. By determining the brain circuitry activated by rewarding drug injections, much can be learned about the degree to which there is a common basis for the abuse liability of seemingly different drugs. The brain circuitry activated by two classes of abused drugs, psychomotor stimulants and opiates, is now partially understood; the current evidence suggests a shared mechanism of stimulant reward and opiate reward. The identified portion of the circuitry involves dopamine-containing cells of the ventral tegmental area and their fiber projections to the cells of the nucleus accumbens. Morphine activates these cells in the region of the cell bodies; it may have direct actions on receptors imbedded in the dopaminergic cell membrane, or it may act on afferent terminals that synapse on the dopaminergic cell bodies or dendrites. Cocaine and amphetamine act at the terminals of the dopaminergic fibers to nucleus accumbens and perhaps other structures. The shared activation of the dopaminergic input to nucleus accumbens accounts for the behaviorally activating and the rewarding effects of both stimulants and opiates (the opiate stimulant action is not widely known because it is usually masked by depressant actions of opiates in other, antagonistic, brain circuits). The activation of dopaminergic systems also accounts for amphetamine euphoria; it almost certainly accounts for cocaine euphoria and it probably accounts for opiate euphoria as well. Opiates and psychomotor stimulants clearly have many other actions which are not shared; nonshared actions must account for the well-known differences in the subjective effects of opiates and stimulants. One of the major nonshared actions is physical dependence. Opiates gain access to a major component of the circuitry mediating opiate physical dependence through opiate receptors in the periaqueductal gray matter. This receptor population is anatomically distinct from the population mediating the rewarding effects of opiates in nondependent animals. While both opiates and stimulants can activate (though by quite different mechanisms and at quite different loci) the dopaminergic circuitry underlying reward phenomena, only opiates activate the separate circuitry underlying dependence phenomena.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2893433 TI - Clinical psychopharmacology and inpatient psychiatry: the revolution, its achievements and its dangers. PMID- 2893432 TI - Clinical selection of benzodiazepine hypnotics. PMID- 2893434 TI - Characterization of specific somatostatin binding sites in guinea pig lung. AB - Somatostatin binding sites have been demonstrated in the cytosolic fraction of guinea-pig lung. Binding of 125I-Tyr11-somatostatin was dependent on time and temperature, saturable, reversible and highly specific. Under equilibrium condition, i.e. 60 min at 25 degrees C, native somatostatin inhibited tracer binding in a dose-dependent manner. Two types of somatostatin binding sites were defined by Scatchard analysis: a small population with a high affinity (Kd = 23.4 nM) and a large population with a low affinity (Kd = 253.5 nM) for somatostatin. The biphasic nature of the dissociation process confirmed the heterogeneity of somatostatin binding sites. Apart from somatostatin, no peptide (1 microM) tested influenced the binding of 125I-Tyr11-somatostatin. The present data represent the first analysis of somatostatin binding sites in lung. PMID- 2893435 TI - Effect of sensitization on somatostatin concentration and binding in cytosol from guinea pig airways. AB - In guinea pigs sensitized with 1 microgram ovalbumin together with 100 mg Al(OH)3, somatostatin levels were selectively increased up to two and 3 times in tissue extracts from trachea and bronchi, respectively, but not in lung as compared to controls. The increase of somatostatin levels observed in trachea and bronchi after sensitization was associated with a decrease in the binding capacity of both high- and low-affinity binding sites (without changes in the affinity values) in the corresponding cytosolic fractions. These results suggests that an increase in airways somatostatin content may be involved in the pathogenesis of anaphylactic bronchoconstriction. PMID- 2893436 TI - Localization in the gastrointestinal tract of immunoreactive prosomatostatin. AB - Antisera against 5 different regions of the entire prosomatostatin molecule were used for immunohistochemical mapping of prosomatostatin-containing structures in the pig gastrointestinal tract, and for radioimmunological and chromatographical analysis of the products of prosomatostatin in extracts of ileal mucosa. The latter showed that the antisera were capable of identifying components containing N-terminal as well as C-terminal parts of prosomatostatin. Endocrine cells were identified with all antisera in most parts of the gastrointestinal tract, and varicose nerve fibres were observed in all parts of the small intestine but not in the stomach and the colon. The colon contained very few immunoreactive structures. Immunoreactive nerve cell bodies were found in the submucous plexus of the small intestine. All immunoreactive endocrine cells in the stomach and the duodenum and all immunoreactive nerves were stained by all 5 antisera whereas the small intestinal endocrine cells did not stain for the most N-terminal region of prosomatostatin. The results suggest that all gastrointestinal somatostatin is derived from the same precursor molecule, which, however, in the small intestinal endocrine cells is processed differently from that of the other tissues. PMID- 2893437 TI - Pressor, tachycardic and feeding responses in conscious rats following i.c.v. administration of dynorphin. Central blockade by opiate and alpha 1-receptor antagonists. AB - Experiments were designed to determine the hemodynamic responses of conscious, unrestrained rats given intracerebroventricular (i.c.v.) injections of dynorphin A-(1-13) and the possible central receptor mechanisms mediating those changes. Male Sprague-Dawley rats (300 gb. wt.) received i.c.v. injections (by gravity flow in a total volume of 3 or 5 microliter) of control solutions of sterile saline (SS) or dimethylsulfoxide (DMSO) or 1.5, 3.0 or 6.1 nmol of dynorphin A-(1 13). Blood pressure and heart rate changes were monitored over 2 h after administration; as well, feeding activity was visually assessed and scored over this period. Other groups of conscious rats were pretreated i.c.v. with equimolar doses (3.0-24.4 nmol) of specific receptor antagonists (naloxone HCl, phentolamine HCl, propranolol HCl, yohimbine HCl or prazosin HCl) 10 min before subsequent i.c.v. administration of SS or DMSO/SS or 6.1 nmol of dynorphin A-(1 13). I.c.v. injection of dynorphin A-(1-13) caused a dose-related pressor response, associated temporally with tachycardia. As well, dynorphin evoked feeding activity and some grooming, which occurred when the rats were hypertensive and tachycardic and decreased as heart rate and blood pressure returned to control levels. I.c.v. pretreatment studies indicated that naloxone HCl (12.2 nmol), phentolamine HCl (12.2 nmol) and prazosin HCl (6.1 nmol) blocked the pressor response, tachycardia as well as feeding activity of rats subsequently given dynorphin. The results suggest the pressor and tachycardic effects of conscious rats following i.c.v. dynorphin administration may, in part, be due to behavioral activation (feeding). As well, these data indicate that both opioid as well as alpha 1-adrenergic receptors within the CNS are involved in mediating the pressor, tachycardic and feeding responses of conscious rats given i.c.v. injections of dynorphin A. PMID- 2893439 TI - Hepatic collagen content and lysyl oxidase activity in rats fed a low protein ethanol diet. AB - To study the effects of chronic ethanol feeding with dietary protein deficiency on hepatic fibrosis, the hepatic contents of triglyceride and collagen, and lysyl oxidase activity in the liver were measured in rats fed ethanol with or without a low protein diet for 7 weeks. In the standard-ethanol diet group, hepatic triglyceride content was increased as compared with that in the standard diet group, but hepatic collagen content was not altered. In the low protein-ethanol diet group, hepatic contents of triglyceride and collagen, especially of insoluble collagen, were increased as compared with those of the low protein diet group. Under these experimental conditions, hepatic lysyl oxidase activity was higher in the low protein-ethanol group as compared with those in other three groups, and was correlated significantly with hepatic collagen content. These data suggest that ethanol feeding with a low protein diet resulted in an increased deposition of collagen in the liver, and that hepatic lysyl oxidase activity is one of the factors responsible for collagen deposition. PMID- 2893438 TI - T cell regulatory disturbances in the rheumatic diseases. AB - Significant immunoregulatory abnormalities have been described in both SLE and RA. In SLE, deficient suppressor T cell activity may result from depletion of CD8+ suppressor precursors, depletion of CD4+ suppressor-inducer cells, or impaired lymphokine production and deficient CD4+ cell activation of suppression by CD4+ cells. The net result is an apparent failure to inhibit antibody synthesis. The defects in RA are less well defined, although in RA there also is evidence that either deficient suppression or deficient suppression-induction plays a role in the pathogenesis of disease. There is evidence for local lymphocyte activation in the synovium, with possibly impaired local immunoregulation. However, the precise nature of the immune reactions in the synovium and their relationship to systemic immunoregulatory abnormalities remain unclear. PMID- 2893440 TI - [Psychotropic drugs in internal medicine. III. Uses and indications in non psychiatric patients]. PMID- 2893441 TI - [Treatment of male non-complicated acute gonorrhea with a single dose of a combination of sodium penicillin and clemizolpenicillin, plus probenecid]. PMID- 2893442 TI - [Current classifications of depression and their effects on prognosis and therapy]. PMID- 2893443 TI - Molecular weight analysis of Entamoeba histolytica antigens recognized by IgG and IgM antibodies in the sera of patients with amoebiasis. AB - The sera of four patients with amoebic liver abscess and two patients with diarrhea caused by Entamoeba histolytica were tested on "Western blots" prepared from E. histolytica strains A3, SFL-3 and HK-9 separated by SDS-PAGE. IgG antibodies in the sera from patients with liver abscess were found to react with several "major" (i.e. strongly staining) band of approximate molecular weights 150-250 kD, 100 kD, 80 kD, 60 kD, 35 kD, 30 kD, 20 kD, and 5-15 kD and the 150 250 kD group of bands. A comparison of the patterns of reactivity obtained with these sera and strains A3, SFL-3 and HK-9 would indicate that some of these bands, especially the 5-15 kD groups of bands might carry antigenic determinants specific for individual strains of amoebae. This 5-15 kD group of bands is completely pelleted at 30.000 g and could therefore be associated with the cytoplasmic membrane. The 150-250 kD group of bands consists of smaller subunits of 40-65 kD molecular weight linked by disulfide bridges; the respective proteins are sensitive to digestion with elastase but not with trypsin, and seem to carry antigenic determinants containing sugar residues as evidenced by their sensitivity to treatment with NaJO4. PMID- 2893444 TI - Course of Entamoeba histolytica infection in nude mice. AB - The course of intestinal infection by Entamoeba histolytica was examined in nu/nu BALB/c mice. Mice were inoculated intracecally with 2.5 X 10(5) polyxenic trophozoites and killed at various times after injection. There was no significant difference in the number of E. histolytica trophozoites recovered in the ceca of nu/+ and T cell-deficient nu/nu mice for the first 25 days after amebic injection. Thirty days following amebic injection the number of trophozoites recovered in the ceca of nu/nu mice was significantly higher than the control mice. Silica treatment increased the growth of parasites in the ceca of nu/nu mice when compared with control groups. These data suggest that both macrophages and T lymphocytes play an important role in host defense against amebic infection in nude mice. PMID- 2893445 TI - Coping with school phobia. PMID- 2893446 TI - The effects of naloxone and timolol on plasma catecholamine levels during short term dynamic exercise. AB - In order to study the role of opioid- and betareceptors on exercise-induced catecholamine responses, the effects of acute intravenous administration of 1 and 4 mg naloxone and of the non-selective betablocker timolol 2 mg of on circulating concentrations of adrenalin, noradrenaline and dopamine during exercise to exhaustion were examined in eight normal, healthy young men, using a double blind, randomized, placebo-controlled design. During maximal exercise, adrenalin levels increased from 71 +/- 17 to 821 +/- 235 pg/ml (p less than 0.05), noradrenaline from 355 +/- 58 to 4235 +/- 1031 pg/ml (p less than 0.05), and dopamine from 72 +/- 20 to 178 +/- 44 pg/ml (p less than 0.05). Naloxone did not influence basal or exercise-induced noradrenaline responses. Timolol clearly augmented peak adrenalin concentration at maximal exercise capacity (1543 +/- 510 pg/ml, p less than 0.05). Basal noradrenaline level was increased (546 +/- 86 pg/ml, p less than 0.05), while exercise-induced noradrenaline level was reduced (2954 +/- 594 pg/ml, p less than 0.05) in proportion to the reduction in maximal exercise capacity during timolol treatment. Neither naloxone nor timolol affected dopamine levels. No additive effect was seen with the combination of naloxone and timolol. It is concluded that the opioid peptides are probably not involved in noradrenaline and dopamine responses, whereas betablockers change the catecholamine response to short-term maximal exercise. PMID- 2893447 TI - Effect of the somatostatin analogue SMS 201-995 on ATP-dependent calcium transport of basolateral vesicles from human duodenum. AB - Brush border membrane vesicles (BBMV) and basolateral membrane vesicles (BLMV) were simultaneously prepared from surgically resected pieces of morphologically intact human duodenum with a modified Percoll gradient centrifugation method. Alkaline phosphatase was enriched 20-fold in BBMV, whereas (Na+ + K+)-stimulated adenosine triphosphatase was enriched 15-fold in BLMV. BBMV and BLMV were preincubated with 3 microM synthetic somatostatin-14 or 3 microM SMS 201-995 for 10 min at 5 degrees C. In BBMV calcium, sodium, D-glucose, L-alanine, and D mannitol uptake was unaffected by somatostatin-14 and SMS 201-995. In BLMV we found two Ca++ transport systems: Na+/Ca++ exchange and ATP-driven Ca++ transport. Somatostatin-14 had no effect on either of the two transport mechanisms. SMS 201-995 had no effect on Na+/Ca++ exchange but significantly inhibited basolateral ATP-dependent Ca++ transport (-40% +/- 5%, p less than 0.005). PMID- 2893448 TI - Pharmacological effects of secretin and somatostatin on gastric and renal function in man. AB - In this randomized, double-blind, placebo-controlled study therapeutic doses of synthetic secretin (0.5 CU/kg/h) and somatostatin (3.5 micrograms/kg/h) given an intravenous infusion suppressed significantly peptone-stimulated gastric acid output per 3 h in nine male healthy subjects from 59.2 +/- 7.4 mmol H+ (placebo) to 16.9 +/- 3.1 and 6.6 +/- 1.5 mmol H+, respectively. Peptone-stimulated gastrin release was reduced to basal concentrations by both hormones. In five subjects secretin raised serum lipase to pathological concentrations. Somatostatin diminished significantly mean blood glucose concentrations. Both had opposite renal effects; secretin showed diuretic and somatostatin antidiuretic properties. Secretin and somatostatin were well tolerated. It is concluded from these data that therapeutic doses of secretin and somatostatin are comparably effective on exocrine and endocrine gastric functions, but have opposite effects on renal functions in man. PMID- 2893449 TI - Outcome of long-term treatment of rheumatoid arthritis with second-line agents. PMID- 2893450 TI - The pharmacokinetics of sulphasalazine in young and elderly patients with rheumatoid arthritis. AB - The clinical pharmacokinetics of enteric-coated sulphasalazine (Salazopyrin-EN) were studied after acute and chronic dosing in 20 patients with 'active' rheumatoid arthritis. 12 elderly (mean age 74.4 +/- 1 yr; range 71-83) and 8 young (mean age 40.5 +/- 1.4 yr; range 35-46) patients were given a single 2 g oral dose of sulphasalazine after an overnight fast. Serum and urine samples were collected at regular intervals over a 96 hour period for estimation of concentrations of sulphasalazine, sulphapyridine and its metabolites. This procedure was repeated after 17 days of continuous treatment with salazopyrin-EN 2 g daily in order to compare the drug's kinetics at 'steady-state'. Whilst the interindividual variation in kinetic parameters was large, age and acetylator status had a significant influence on a number of factors. The elimination half life of sulphasalazine was prolonged in the elderly whilst renal clearance was increased in slow acetylators at 'steady-state'. The tmax and apparent volume of distribution of sulphapyridine were increased in the elderly after a single drug dosage but these differences disappeared with regular dosing. The Cmax, elimination half-life, 'steady-state' serum concentration, apparent volume of distribution and total clearance of sulphapyridine were all affected by acetylator status. We conclude that old age has only a minor effect on the body's handling of sulphasalazine and sulphapyridine but that acetylator phenotype plays a significant role in determining the 'steady-state' serum concentrations of sulphapyridine. This is likely to have practical implications with regard to some of the drug's adverse effects. PMID- 2893451 TI - Long term experience of salazopyrin EN in rheumatoid arthritis (RA). AB - Our studies have shown that Salazopyrin EN is an effective slow-acting anti rheumatic drug, improving clinical synovitis, depressing the acute phase response, capable of inducing remissions and possibly influencing the progression of joint damage. It is well-tolerated in the long-term with comparatively few serious side effects. Its mechanism of action, however, is still not entirely clear. We have found that the sulphapyridine moiety penetrates the synovial membrane and also that it can modify immune function. While Salazopyrin undoubtedly has an important role in the therapy of rheumatoid arthritis, it probably also has a place in the treatment of seronegative arthropathies and the spondyloarthritides. Furthermore we suggest that it should be used as an anchor drug in combination therapy to attempt to suppress disease activity further and limit joint damage. PMID- 2893452 TI - New data intensify the agony over ecstasy. PMID- 2893453 TI - Legal limbo for ecstasy. PMID- 2893455 TI - Utility of the health belief model in examining medication compliance among psychiatric outpatients. AB - This study investigates the relationship between health beliefs and medication compliance among a group of psychiatric outpatients who were prescribed antipsychotic drug regimens. The method of study was an interview with 107 outpatients discharged from two Veterans Administration Medical Centers. The health belief model (HBM) served as an organizing framework to explore the relationships among perceptions of illness severity, susceptibility, benefits and barriers of treatment, cues to action, and medication compliance. The results provide a systematic description of health beliefs reported by psychiatric outpatients. Analyses examine the ability of beliefs to predict compliance and affirm the model's theoretical cogency and appropriateness for use with psychiatric outpatients. Regression analysis showed that 20% of the total variance in compliance could be explained when all components of the HBM were examined together. The study supported the concepts that psychiatric outpatients hold identifiable patterns of health beliefs and attitudes and that the health belief framework functions best when utilized as an integrated model to examine compliance. PMID- 2893454 TI - Molecular cloning of a feline leukemia virus that induces fatal immunodeficiency disease in cats. AB - A replication-defective variant of feline leukemia virus was molecularly cloned directly from infected tissue and found to induce a rapid and fatal immunodeficiency syndrome in cats. Studies with cloned viruses also showed that subtle mutational changes would convert a minimally pathogenic virus into one that would induce an acute form of immunodeficiency. The data suggest that acutely pathogenic viruses may be selected against by current methods for isolation of the human and simian immunodeficiency viruses. PMID- 2893456 TI - The coding sequence for the human 18,000-dalton hydrophobic pulmonary surfactant protein is located on chromosome 2 and identifies a restriction fragment length polymorphism. AB - The 18-kd hydrophobic pulmonary surfactant protein (PSP-B) is a developmentally regulated protein which is important for normal lung function. A complementary DNA probe for 221 NH2 terminal amino acids of PSP-B was used to determine the chromosomal location of this gene and identify a restriction fragment length polymorphism (RFLP). Southern blot hybridization to genomic DNA isolated from a panel of human-CHO somatic cell hybrids unambiguously maps this gene to chromosome 2. Human DNA cut with BamHI yields a RFLP with variable bands at 2.8 and 2.6 kb. Since there is a relative lack of polymorphic markers for chromosome 2, this sequence may be useful in linkage analysis. PMID- 2893457 TI - Takayasu's arteritis in pregnancy. A report of 4 cases. AB - Four cases of Takayasu's arteritis in association with pregnancy are described. These patients are at high risk of pregnancy hypertension. Measurement of the blood pressure in the arms may be impossible or unreliable and is often more accurately obtained in the legs. PMID- 2893458 TI - Routine teratogenicity test that uses chick embryos in vitro. AB - An in vitro culture of chicken embryo is described: the embryos at the stage of gastrulation are explanted from eggs into transparent silicone chambers where they continue to develop normally under controlled conditions for additional 3 d. This period corresponds to 2-5 wk of postconceptional age in the human embryo. In both the chick and man, this period is very sensitive to physicochemical perturbations which can lead to surviving malformations. Six chemical agents were tested with this culture: methotrexate, cadmium chloride, caffeine, phenobarbital, aspirin, and saccharin. Survival scores, growth perturbations, and early signs of anomalies of the nervous, skeletomotor, and cardiovascular systems were analyzed with respect to the used concentrations. The dose-response curves were obtained with good precision and allowed a discrimination between the teratogenetic and unspecific toxic effects and a comparison of the toxic potency of the six drugs. The evaluation of one drug took, roughly, 3 wk, one technician, and about 150 eggs. The advantages (simplicity, rapidity, reproducibility, specificity, economy, no suffering, and no use of mature animals) and disadvantages (nonmammalian species, absence of detoxicating organs) of the method are discussed. The method is proposed as a routine teratogenicity and embryotoxicity test which allows primary screening of many compounds and which can thus substantially reduce the ultimate experiments that use pregnant mammalian females. PMID- 2893459 TI - Late-onset cerebellar degeneration in mice induced transplacentally by methylnitrosourea. AB - A late-onset degenerative disease in the cerebellum was produced in the offspring of mice exposed to 1 mg/kg of the direct-acting DNA alkylating agent methylnitrosourea (MNU) on day 16 of gestation. This intrauterine exposure to MNU also provoked a progressive retinal degeneration that was described elsewhere. Mild ataxia in the MNU-exposed animals was expressed by 20 weeks of age. Although animals appeared normal in the immediate post-natal period, quantitative histological evaluation of cerebellar coronal sections indicated that MNU-exposed animals had a significantly greater number of pyknotic Purkinje cells than age matched controls. The number of pyknotic Purkinje cells declined with age in the drug exposed animals; however, the percentage of pyknotic Purkinje cells to total number of Purkinje cells still was greater in MNU-induced animals at 36 weeks than in controls, suggesting that a slow degenerative process was ongoing in the MNU-exposed animals. Furthermore, the folia were grossly disrupted in 90% of the older MNU-exposed animals (ages greater than 12 weeks), suggesting permanent cerebellar disruption macroscopically. Such intrauterine exposure to low doses of alkylating agents may be potentially useful in modeling degenerative neuronal diseases. PMID- 2893460 TI - The covalent binding of 1,1,2,2-tetrachloroethane to macromolecules of rat and mouse organs. AB - The in vivo interaction of the hepatocarcinogen 1,1,2,2-tetrachloroethane (1,1,2,2-TTCE) with DNA, RNA, and proteins of male Wistar rats and BALB/c mice was measured 22 hr after i.p. injection. Covalent binding index (CBI) to liver DNA was about 500 and was comparable to those of carcinogens classified as moderate initiators. It was higher than those of other chloroethanes, even than that of 1,2-dichloroethane (1,2-DCE), a symmetrically substituted haloethane whose genotoxicity has been widely demonstrated. In in vitro cell-free systems, 1,1,2,2-tetrachloroethane was bioactivated by mixed-function oxidase(s) and glutathione-S-transferase(s) (GSH-T) from microsomal and cytosolic fractions of rat and mouse liver and, to a lesser extent, of mouse lung. The in vitro activation led to formation of reactive species capable of binding to exogenous DNA and to the subcellular constituents of enzymatic fractions. These data, along with previous literature reports, provide sufficient evidence of 1,1,2,2-TTCE genotoxicity. PMID- 2893461 TI - Analysis of diurnal difference in teratogen (Ara-C) susceptibility in mouse embryos by a progressive phase-shift method. AB - Our objectives were to determine whether the embryotoxic and teratogenic potential of cytosine arabinoside (Ara-C) differs depending on the time of day. Pregnant CD-1 (ICR) mice were placed in an environment where the phases of lighting and darkness were reversed by progressive phase-delay or phase-advance methods--2 h every day from day of gestation (dg) 2 to dg 7 (or 6). After it was confirmed that these progressive phase-shifting methods had no effect on embryonic growth and pregnancy outcome, 5 mg/kg body weight (bt) of Ara-C was injected intraperitoneally into these animals at 1000 or 1600 on dg 11, and the incidence of gross fetal malformations was compared with that in control dams treated similarly but under a regular lighting regimen (0600-1800). In contrast to previous reports on other teratogens, no diurnal difference was observed in fetal susceptibility to the teratogenic potential of Ara-C. The possible usefulness of the progressive phase-shifting method in the field of chronoteratology is proposed. PMID- 2893462 TI - In vitro embryotoxic effects of ethylene glycol in rats. AB - Rat embryos of the CD strain were treated in a whole embryo culture system with either 30 or 40 microliters of ethylene glycol (EG) per milliliter of culture medium for the first 8 (0-8 hr) or second 8 (8-16 hr) hr of a 48-hr culture period. The compound was not embryolethal under these conditions but did alter growth and development. EG at 40 microliters/ml of culture medium at 8-16 hr decreased morphological score, somite number, crown-rump and head lengths, as well as DNA and protein contents. The most frequent abnormality induced by the compound was absence of yolk sac circulation; absent hindlimb bud, hypoplastic telencephalon, and lack of development of the otic and optic systems were also seen in EG-exposed embryos. Since it has been reported that rodent embryos cultured in vitro lack alcohol and aldehyde dehydrogenases that metabolize EG, present results suggest that the parent compound is capable of altering normal embryonic development when administered during a brief period or organogenesis. PMID- 2893463 TI - Prenatal and postnatal antimony exposure in rats: effect on vasomotor reactivity development of pups. AB - Pregnant female rats were exposed to antimony trichloride (0.1 and 1 mg/dl in their drinking water ad libitum) from the first day of pregnancy until weaning (22nd day after delivery). Pups were exposed to antimony trichloride (0.1 and 1 mg/dl in their drinking water ad libitum) from 22nd until 60th day of age. Antimony exposure did not significantly affect maternal and pup systolic arterial blood pressure, length of gestation, and number of newborn per litter. Antimony exposure decreased maternal and pup body weight. No macroscopic teratogenic effects have been observed. Whether or not pups were exposed to antimony trichloride, pressor responses to carotid occlusion and 1-noradrenaline and hypotensive responses to 1-isoprenaline and acetylcholine were significantly higher on the 60th than on the 30th day of age. In pups, prenatal and postnatal antimony exposure did not affect pressor response to carotidal occlusion, while it decreased pressor response to 1-noradrenaline and hypotensive response to 1 isoprenaline on the 60th day after birth. At last, antimony exposure at higher concentration decreased pup hypotensive response to acetylcholine on the 60th day. PMID- 2893465 TI - Studies on the ability of hypotonic solutions to induce chromosomal aberrations in V 79 cells. AB - V 79 hamster cells were exposed to hypotonic culture medium or to hypotonic solutions of ammonium sulfate, sodium chloride, or trishydroxymethylaminomethane. Hypotonic treatment led in all experiments to a clear increase of chromosomal aberrations. Reasons for the aberrations observed may be directly induced DNA damage such as double strand breaks or a release of DNase after lysosomal damage because of the hypotonic treatment. Other reasons involved in the aberration production may be changes of the internal pH or damage of the chromosomal proteins. PMID- 2893464 TI - Depression of glutathione in male reproductive tissues and potentiation of EMS induced germ cell mutagenesis by L-buthionine sulfoximine. AB - Buthionine sulfoximine (BSO) treatment significantly reduced testicular epididymal and vas deferens glutathione (GSH) levels in rats. Testicular levels of GSH were reduced by 20%, while epididymal GSH levels were reduced by more than 50%. BSO treatment correspondingly enhanced ethyl methanesulfonate (EMS)-induced dominant lethal mutations. EMS-induced resorption rates were doubled following BSO treatment. This effect was observed in mating wk 2 and 3 (d 8-19 following treatment), indicating effects on those germ cells which were in late testicular stages or were caput epididymal spermatozoa at the time of EMS treatment. The enhancement of the mutagenic action of EMS by BSO is restricted to the same time period (spermatid-spermatozoa transition, early epididymal maturation) as maximum sensitivity to the clastogenic action of EMS on male germ cells. The temporal pattern of EMS alkylation of rat spermatozoa correlated with the incidence of EMS induced dominant lethal mutations. BSO depresses GSH in the male reproductive tract in a dose- and time-dependent manner. Perturbation of GSH in the male reproductive tract appears to influence chemical-induced germ cell mutations. PMID- 2893466 TI - Leukemias and blood dyscrasias following exposure to chlordane and heptachlor. AB - We present 25 new cases of blood dyscrasia, including leukemias, production defects, and thrombocytopenic purpura, generally following home termite treatment with the chlorinated hydrocarbon pesticides chlordane and heptachlor (C/H). These newly reported cases are consistent with 34 previously published case reports associating blood dyscrasias with C/H exposure. Additionally, the newly reported leukemias are consistent with epidemiologic evidence of excess risk of leukemia and other cancers in C/H-exposed populations and with the carcinogenic action of C/H in animals. The importance of case reports in warning of the association of blood dyscrasias to C/H exposure is emphasized. Until the voluntary halt in production in July 1987, millions of homes in the United States were treated with chlordane and heptachlor for termites even though their agricultural uses were phased out in 1978, largely on the grounds of "imminent hazard" because of carcinogenicity. In view of the recognized myelotoxicity, carcinogenicity, and other chronic toxic effects of these pesticides, a national program for monitoring all homes treated is urgently needed to detect persistent contamination. PMID- 2893468 TI - Factors influencing the initiation by gamma rays of hepatocarcinogenesis in the rat. AB - F344 male rats were irradiated once with 6 G of cesium 137 gamma rays at various times after a two-thirds partial hepatectomy (PH) and then fed a diet containing the liver tumor promoter phenobarbital to evoke the expression of initiated hepatocytes. Yields of hepatocellular neoplasms were enumerated at 45 weeks after irradiation. Although proliferating hepatocytes in regenerating livers appeared to have increased risk of initiation by gamma rays, there was no apparent variation in risk among groups that were treated at times when hepatocytes were in different portions of the cell cycle (G1, S, G2/M). Gamma irradiation delayed the onsets of DNA synthesis and mitosis by proliferating hepatocytes by 18-20 h. The rate of rejoining of radiation-induced DNA strand breaks was analyzed in primary cultures of hepatocytes; 98% of the strand breaks were rejoined within 30 min after irradiation. Efficient repair of certain types of radiation-induced damage to DNA before the damaged DNA is replicated should cause a substantial reduction in the probability of induction of base-substitution mutations. Hepatocellular islands and neoplasms that were initiated by gamma rays may be derived from proliferating hepatocytes which incurred other radiation-induced DNA damages such as chromosomal aberrations. PMID- 2893467 TI - Variable patterns in anticonvulsant drug-induced malformations in mice: comparisons of phenytoin and phenobarbital. AB - Anticonvulsant drugs are known to induce a varied pattern of malformation in both humans and in experimental rodent models. Often the clinical overlap between the pattern of defects induced by different anticonvulsant drugs is so striking that many clinicians question the role these compounds play relative to the existing maternal seizure disorder in the etiology of the observed malformations. In three inbred mouse strains exposed to phenytoin or phenobarbital in utero, the pattern of malformation differed markedly. From the types of anomalies observed, it is apparent that phenobarbital induced more malformations, while phenytoin produced a higher frequency of anomalies related to incomplete development. Thus, while there exists a certain degree of similarity between some of the minor features characteristic of each drug-induced syndrome, there are distinct differences in pregnancy outcome in experimental animals exposed to these drugs. Given the fact that phenobarbital induces more malformations that can be traced to exposure during early organogenesis, it may be wise to consider a therapeutic strategy in which phenytoin is utilized only during organogenesis, and is then replaced with phenobarbital for the remainder of the pregnancy. PMID- 2893469 TI - [Atopic dermatitis in dogs: therapeutic possibilities]. AB - The possibilities of treatment in canine atopy are discussed. Varying with the age of the dog, the duration and seasonal pattern of the disease, and the number of causative allergens, withdrawal therapy, administration of glucocorticosteroids or hyposensitisation may be chosen. PMID- 2893470 TI - DX alpha gene polymorphism in Graves' disease. AB - An HLA-DX alpha gene polymorphism was analysed by Southern blotting in 49 British patients with Graves' disease and 61 control subjects. Two previously described allelic fragments of Taq I digested genomic DNA at 2.1 kb (U) and 1.9 kb (L) were found. The genotype frequencies for UU, UL and LL did not differ from the controls in Graves' disease, either for the whole groups or when subdivided into HLA-DR3-positive and -negative subjects. There was a significant association of the U allele with HLA-DR3 in both controls (P less than 0.05) and Graves' disease (P less than 0.025). The results indicate that DX alpha polymorphism is not primarily associated with Graves' disease. The findings differ from recent studies which showed that DX alpha polymorphisms may contribute to susceptibility in other DR3-associated autoimmune diseases. PMID- 2893471 TI - Alterations in the hepatic glucocorticoid response to mirex treatment. AB - Corticosterone has been shown to be involved in the regulation of mirex-induced adaptive liver growth. To further investigate the role of corticosterone in this response, plasma corticosterone, hepatic tyrosine aminotransferase (TAT) activity, and hepatic cytosolic binding of glucocorticoids were determined in male Sprague-Dawley rats following a single oral dose of mirex (100 mg/kg body wt). Mirex stimulated a significant elevation in plasma corticosterone levels 12 and 24 hr after dosing; however, hepatic tyrosine aminotransferase activity was not induced above control levels 6, 12, or 24 hr after mirex dosing. Mirex does not appear to directly inhibit the enzyme because tyrosine aminotransferase activity was increased in a dose-dependent manner in both intact and adrenalectomized rats when corticosterone supplements (1-50 mg/kg body wt) were given after mirex dosing. In an effort to explain the lack of hepatic TAT induction, the concentration of cytosolic binding sites for [3H]dexamethasone in intact, adrenalectomized, and adrenalectomized corticosterone-supplemented rats was measured 12, 24, and 48 hr after mirex dosing. There was a significant decrease in the total concentration of cytosolic binding sites for [3H]dexamethasone 12 and 48 hr after mirex dosing in intact rats, 12 and 48 hr after mirex dosing in adrenalectomized rats, and 12 and 24 hr after mirex dosing in adrenalectomized corticosterone-supplemented rats. There was a significant increase in the apparent dissociation constant (Kd) in intact rats dosed with mirex as compared to the oil controls, but there was no difference in Kd after mirex dosing in the adrenalectomized (ADX) rats when compared to the Kd for the oil-dosed control rats. The maximal binding capacity (Bmax) was not significantly different from oil controls after mirex dosing in either intact or ADX rats. The lack of hepatic TAT induction in the presence of increased plasma levels of corticosterone appears to be related to glucocorticoid receptor alterations in the liver of intact rats. PMID- 2893472 TI - Circadian variations in the renal toxicity of gentamicin in rats. AB - The hypothesis that sublethal doses of aminoglycosides cause renal tubule disorders resulting in changes of urine enzyme levels was investigated. The renal status following injection of a single sublethal dose of gentamicin (200 mg/kg) at different times during a 24 h cycle was studied. Increased excretion of gamma glutamyl transferase, alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase, used clinically as markers for tubule toxicity of aminoglycosides, was maximal when gentamicin was administered to rats at 2 p.m. and was minimal when injected at 8 p.m. These significant differences in enzyme excretion as a function of injection time are correlated with the concentration of gentamicin in the urine and in the renal cortex. PMID- 2893473 TI - Advances in experimental studies and clinical application of fetal liver cells. PMID- 2893474 TI - What kind of morphologically recognizable haemopoietic cells do we inject when doing foetal liver infusion in man? AB - There is no agreement, how to define the age of the embryo/foetus. From the 15th (fertilization) week onwards the whole foetal liver contains some 10(9) free haemopoietic cells. Before, and up to the 30th-34th weeks, the liver is the main site of haemopoiesis. The differential of embryonic smears (up to wk 9) differs from that of foetal ones. The first invasion of circulating primitive erythroblasts seeding in the liver (early 5th wk) is accompanied by the appearance of a lot of sinusoidal macrophages. Definitive erythropoiesis expands during the 6th-7th wks. Granulocytic representation peaks at 15-16 wks. Megakaryocytes are small and have few nuclei/nuclear lobes. Five to 8, or even more per cent of single haemopoietic cells were lymphoid-like cells in the 5th 6th wk liver smear. These cells precede the development of any lymphoid structure in the foetus. Ordinary lymphocytes amount to less than 2% between 10 and 18 wks, and reached 3% at wk 24. Percentage of dyserythropoietic nuclei in smears has been used to decide whether the injected cells could be regarded as 'physiological' cells. Ten out of 11 apparently healthy foetuses, delivered by hysterectomy/hysterotomy for maternal interest, aged 10 1/2 to 20 1/2 weeks, had mean 4.5% liver dyserythropoiesis. Extremely high dyserythropoiesis was associated with multilineage, instead of overwhelmingly erythroid haemopoiesis. PMID- 2893475 TI - Survey of experimental data on fetal liver transplantation. AB - Fetal liver transplantation has been shown to induce hematological and immunological reconstitution in irradiated rodents, dogs, horses, and sheep. Engraftment and reconstitution without GvHD has been readily obtained using histocompatible donors. When mismatched fetal donors were used, a comparatively larger number of donor cells was required, in addition to pre-treatment of host with higher doses of irradiation or irradiation plus chemotherapy. Stem cell suspensions devoid of any T lymphocyte can be transplanted across major histocompatibility barrier without inducing overt GvHD. The transplanted animals become tolerant to both donor and host grafts. PMID- 2893476 TI - Fetal liver infusion in aplastic anaemia. AB - Forty patients with severe aplastic anaemia received an intravenous infusion of 0.004 to 11.1 x 10(8) (median: 8 x 10(8) hematopoietic cells prepared from the fetal livers of 8-32 week old abortuses. Five patients, who died within 15 days of fetal liver infusion, are excluded from analysis. Twenty-two of the 35 evaluable patients (62%) responded favourably. Six of the 7 patients with good response were alive after 9 to 44 months (median: m = 20); one died 106 months after fetal liver infusion due to renal lithiasis. Four of the 7 with moderate response were alive after 9 to 31 months; 3 died within 16 months. Of 8 patients with minimal response, one was lost to follow-up and the others died in 3.4 to 10 months (m = 6). Median survival of responders was 15.7 months. Bone marrow cellularity became normal in 12 patients following fetal liver infusion. In seven patients, there was a relapse; 6 regained a normal bone marrow cellularity after a second or third fetal liver infusion. These data strongly suggest a role of fetal liver infusion in inducing bone marrow recovery. Of 13 non-responders, 4 were lost to follow-up and 9 died within 20 days-4.3 months (m = 1.6). Fetal liver infusion appears to be an effective therapy in patients with severe aplastic anaemia. PMID- 2893477 TI - [Effect of mononuclear phagocytes on the differentiation of syngeneic, allogeneic and xenogeneic hematopoietic stem cells]. AB - The colony formation in spleen of lethally irradiated syngeneic or hybrid recipients was studied after transplantation of bone marrow cells, with or without macrophages from lymph nodules or from peritoneal cavity of mice, cells of macrophage-like cell line J-774, and monocytes from peripheral blood of healthy donors. The direction of stem cell differentiations in the presence of all the types of mononuclear phagocytes was seen to change from mainly erythroid to mainly myeloid one. The ratio of erythroid to myeloid colonies became equal to 0.5-0.9 instead of 2.0, when bone marrow cells were injected with equivalent quantity of mononuclear phagocytes. This new regulatory function of mononuclear phagocytes is discussed. PMID- 2893478 TI - [Synthesis of glutaminic and aspartic acids in mitochondria of the visual analyzer of the dog brain during postnatal ontogenesis]. AB - It is revealed that glutaminic acid (GA) synthesis by direct reductive amination proves to be the most rapid in the mitochondria of the outer geniculate body (OGB) from the 1st till the 45th day of the postnatal development, and beginning from the 45th day till the 3-month age in visual cortex (field 17) (VC) and bigeminal bodies (BB). It is stated that GA synthesis by transamination in the mitochondria of VC, OGB, and BB proceeds less intensively than by a direct reductive amination at the early stage of postnatal development, being more rapid during the period from the 12-16th till the 45th day of postnatal development. Unlike GA synthesis in the mitochondria of the studied visual analyzer structures of canine brain AsA synthesis is more rapid in transamination reaction at the early stage of postnatal development. The high level of AsA synthesis was observed on the day when the puppies' eyes began to see clearly. The level of AsA synthesis by reductive amination and transamination in the mitochondria of VC, BB, and OGB at the early stage of postnatal development is lower than that of GA synthesis. PMID- 2893479 TI - [Vecuronium (Norcuron). A non-depolarization muscle relaxants with intermediate action]. PMID- 2893480 TI - [Intraabdominal cystic anaplastic seminoma in a 67-year-old man]. PMID- 2893481 TI - [Interaction with disulfiram]. PMID- 2893482 TI - [Ulcer surgery before and after administration of H2 blockader treatment]. PMID- 2893483 TI - [Relation between schizophrenia and cancer]. PMID- 2893484 TI - [Beta blockers following acute myocardial infarct?]. PMID- 2893485 TI - [Adverse reactions during salazosulfapyridine (sulfasalazin) therapy in Denmark 1968-1987]. PMID- 2893486 TI - Lack of circulating thyroid stimulating immunoglobulins in cats with hyperthyroidism. AB - Although feline hyperthyroidism has become a commonly diagnosed disorder of older cats, the underlying etiology remains unknown. Pathological findings of adenomatous hyperplasia involving both thyroid lobes in most hyperthyroid cats suggests the possibility that feline hyperthyroidism may be similar to human Graves' disease, which results from high circulating levels of thyroid stimulating immunoglobulins (TSIs). To exclude high circulating levels of TSIs as the cause of feline hyperthyroidism, we measured intracellular concentrations of cyclic adenosine monophosphate (cAMP) in functioning rat thyroid cells (FRTL-5) incubated with IgG extracted from hyperthyroid cat serum. Since TSIs stimulate thyroid hormone secretion through activation of cAMP, their presence can be evidenced in vitro by generation of high cAMP concentrations in cultured thyroid cells. No significant difference was found in intracellular cAMP concentrations in FRTL-5 cells incubated with IgG from normal versus hyperthyroid cats. In contrast, IgG from a human patient with Graves' disease caused substantially more cAMP generation than either normal human IgG or IgG from the cats of this study. These results indicate that feline hyperthyroidism does not result from high circulating concentrations of TSI and, in that respect, is not analogous to Graves' disease. PMID- 2893487 TI - Milk-borne transmission of human T-cell leukemia virus type I in rabbits. AB - The mode of vertical transmission of human T-cell leukemia virus type I (HTLV-I) was investigated by foster-nursing in rabbits. Two of five rabbits born to noninfected mothers and fostered by virus-infected females seroconverted for HTLV I after 7 weeks, whereas all seven rabbits born to virus-infected mothers and fostered by noninfected females remained seronegative for the observation period of 6 months. Culture of peripheral blood lymphocytes gave rise to an HTLV-I carrying T-cell line from each of the two seroconverted rabbits. These findings suggest that HTLV-I is transmitted through milk from mother to offspring. PMID- 2893489 TI - [Use of the peptide hormone melanostatin and its analogs for the synthesis of new antitumor compounds]. AB - A hypothalamic hormone--melanostatin H-L-Pro-L-Leu-NH2- and its 9 analogs were synthesized and their antitumor properties studied. Melanostatin caused a 52-72% inhibition of tumor growth (p less than 0.05) in mice bearing adenocarcinoma of the mammary gland Ca-755, cervical carcinoma CC-5 and melanoma B-16. Non cytotoxic analogs containing D-leucine or L-lysine showed low activity. Among analogs containing sarcolysine stereomers, chlorphenacyl or chlorambucil, derivatives with L-sarcolysin exerted a high antitumor effect on Ca-755, CC-5, Lewis lung carcinoma, lymphoid leukemia L-1210, sarcoma-37, melanoma B-16 and S 91 (80-99% inhibition of tumor growth, p less than 0.05). L-sarcolysin alone had a higher effect on S-91 only (p less than 0.05). Antitumor effect of melanostatin is due to its amino acid sequences. Melanostatin analogs modified by L phenylalanine retain their antitumor properties. PMID- 2893488 TI - [Dynamics of organ-specific liver enzymes and urocanic acid in patients with gout during complex balneotherapy]. PMID- 2893491 TI - [Isolation of a Tahyna-like virus (Bunyaviridae, Bunyavirus, California encephalitis complex) on northern Sakhalin Island]. AB - The strain LEIV-11483 Sak of Tahyna virus or a virus closely related to it antigenically was isolated from Aedes spp. mosquitoes (predominantly A. communis) collected August 25, 1985, in the light coniferous subzone of the mid-taiga landscape zone in the north of Sakhalin Island (54 degrees N, 142 degrees E). Altogether, 17.8 thousand mosquitoes were examined which were collected in June August, 1985, in the light and dark coniferous subzones of mid-taiga. In the human population, virus-neutralizing antibodies to Tahyna virus were found in 7 18%, to Batai virus in 3%, to Uukuniemi virus in none. PMID- 2893490 TI - [Restriction analysis of the DNA of the toxigenic corynephages BF, phi 984, phi 9 and C]. AB - The results of restriction analysis of toxigenic corynephages BF, phi 984, phi 9, and C are presented. Phage BF was shown to be a deletion derivative of phage beta vir, phage phi 984 to be omega-like. Toxigenic corynephages phi 9 and C belong to a new group of corynephages designated phi. DNA of phages phi 9 and C as well as chromosomal DNA of the indicator strains was not hydrolysed by specific Hind III endonuclease, that is likely to be associated with the presence of a modification system in host strains. PMID- 2893493 TI - [Exact determination of the eastern border of the European portion of the nosogeographic range of the hemorrhagic fever with renal syndrome]. AB - Radioimmunoassay was used for examinations of 21,488 serum specimens from the population of 145 areas of 8 regions and 2 republics. The immune portion comprised 8.8% to the west of the assumed border and 2.7% to the east (t = 20.7). Active natural foci of the infection were found in individual territories located to the east of the assumed border (areas of Saratov Province to the north of the Irgiz River, trans-Ural areas of Bashkiria, southern taiga areas of Sverdlovsk, Tyumen, and northwestern Omsk Provinces). The extreme eastern points of the endemic area are Tevriz, Tary, and Znamenskoe Districts of Omsk Province. The areas of Siberian forest steppe, the steppe areas of western Siberia and those on the left bank of the Volga (Zavolzhye) are free from the infection foci. Natural foci of infection were found in the taiga part of the Komi ASSR, whereas they were absent in the forest tundra zone. PMID- 2893492 TI - [Detection of natural foci of the hemorrhagic fever with renal syndrome in the Georgian SSR]. AB - The circulation of the causative agent of hemorrhagic fever with renal syndrome (HFRS) in Georgia was studied. Altogether, 7,938 small mammals of 16 species trapped in 23 administrative areas of the republic were examined, and the specific antigen of HFRS virus was detected in 308 (3.8%). In serological examinations of 10 patients, antibody to HFRS virus was found in 4. Analysis of the above results indicates the existence of natural foci of HFRS in the Georgian SSR. PMID- 2893494 TI - [Complications in the cardiovascular system from neuroleptic treatment]. AB - The arterial pressure fell abruptly in 23.38% of 124 psychic patients during the first days of treatment with neuroleptics. About two weeks later it gradually rose to its initial values. The patients who do not feel well with the low arterial pressure need peripheral stimulants such as Effortil, Mephentermin, etc. Other complications of the neuroleptic therapy are the rhythm and conduction cardiac disorders (19.96% of the patients over 60 years of age showed rhythm and conduction disorders--polytopic and multiple extrasystoles, ventricular paroxysmal tachycardia, atrioventricular block III degree). These patients need active surveillance and emergency treatment with antiarrhythmic drugs. The modern treatment of psychic diseases with larger doses of neuroleptics requires regular clinical and ECC control, especially in older patients. PMID- 2893495 TI - Health manpower out of balance. PMID- 2893496 TI - Indicators for the measurement of health manpower imbalances. PMID- 2893498 TI - MRI localization of an undescending testicle: case report. PMID- 2893497 TI - HIV and HTLV-I antibody studies: pregnant women in the 1960s, patients with AIDS, homosexuals, and individuals with tropical spastic paraparesis. AB - To investigate the possible occurrence of human immunodeficiency virus (HIV) or human T-cell lymphotropic virus, type I (HTLV-I) infections in the United States prior to 1979-1981, when acquired immune deficiency syndrome (AIDS) was first recognized, we tested sera from 310 pregnant women who participated in the Collaborative Perinatal Project during the period 1959-1964 for HIV and HTLV-I antibody. These samples included sera from 53 pregnant women who were intravenous drug users. The remainder were from women who had cervical epithelial abnormalities, who developed cervical carcinomas, who had had children with erythroblastosis fetalis, who had had children that developed malignant neoplasms early in life, or normal pregnant women. None of the 310 women had confirmed HIV or HTLV-I antibody. The rate of false-positive reactions with the HIV enzyme linked immunosorbent assay (ELISA) antibody test in these long-frozen samples was similar to that observed in fresh sera. HIV antibody was detected in homosexual patients with AIDS; HTLV-I antibody was not detected in any of these sera. HTLV-I antibody was detected in 17 of 20 patients with tropical spastic paraparesis (TSP) and in two of seven patients with other neurological diseases diagnosed as transverse myelopathy and multiple sclerosis, and in none of nine normal controls; HIV antibody was not detected in any of these sera patients. Thus, we conclude that there was no serological evidence of infection with HIV or HTLV-I in the pregnant women studied; however, HIV antibody was present in all AIDS patients tested, and HTLV-I antibody was found in the majority of patients with TSP. PMID- 2893500 TI - [Screening for tetracyclic benzodiazepines using EMIT-st (benzodiazepines) and TDx]. AB - The article reports threshold ranges and detection limits for the screening of tetracyclic benzodiazepines (adinazolam, alprazolam, brotizolam, estazolam, loprazolam, midazolam, triazolam and many metabolites) using the EMIT-st and TDx system (FPIA). In most cases, the cross reactivities of the two systems are comparable, but there are also remarkable differences. Detection limits are mainly in the range between 0.2 and 0.5 mg/l but, in some cases, the limits are also considerably higher. The within-day precision is 1.1% (TDx) and 16.5% (EMIT st); day-to-day precision is 4.7% (TDx) and 12.6% (EMIT-st), respectively. PMID- 2893501 TI - Experiences with Kryptocur in the treatment of cryptorchism. AB - Kryptocur (Gonadorelin, Hoechst) was applied in the form of intranasal spray three times daily in 16 boys. A total of 18 retained testes were treated. Kryptocur causes release of LH and FSH. The hormonal pulse-therapy elevates testosterone level which, in turn, leads to descension of the testis. Side effects are less significant than with HCG. Among the children the youngest was 2.5 and the oldest 9 years old. In seven cases, the testis descended into the scrotum, in three cases migrant testes were resulted, in six cases, there was no result at all. The most favourable effect was achieved in the youngest age-group (2.5 to 5 year-olds) with retained testes lodged at the root of the penis. PMID- 2893499 TI - [Specific and nonspecific components in the neurohumoral link of the conditioned food-refusal reflex in the edible snail]. AB - On snails, the action was studied of hemolymph of donors with conditioned food refusal reflex on acquisition of the same habit by intact snails-recipients in case of coincidence or of difference of conditioned stimuli in donors and recipients. Specific component of the facilitating effect was distinctly manifest at selection of optimal doze of hemolymph and depended on the season. At non optimal parameters of the experiment the specific component of the facilitating effect was masked by the non-specific one, or an inhibitory effect took place. The data obtained testify to multicomponent composition of the neurohumoral link in the mechanism of conditioned reflex formation. PMID- 2893502 TI - Why do beta-blockers prevent sudden death? PMID- 2893503 TI - [Evaluation of the passive particle aggulutination method and enzyme immunoassay for the antibodies to adult T-cell leukemia virus in the sera from healthy adults]. PMID- 2893504 TI - Localization of an abundant myeloid-related sequence. AB - Differential screening of a CML-derived cDNA library was used to isolate a cDNA clone representing an abundant mRNA in leukocytes of chronic phase, chronic myelogenous leukemia (CML) patients. This myeloid-related sequence (mrs) comprises approximately 2% of the chronic phase, CML mRNA. Hybridization of the radiolabeled cDNA to the cellular RNAs of intact, morphologically distinguishable, primary hematopoietic cells indicates that the primary cells producing mrs RNA are eosinophils (Eo), basophils (Baso), promyelocytes (Pro) and myelocytes (Mye). In the neutrophilic series, the abundance of mrs RNA decreases as the cells mature. The mrs RNA potentially encodes a 93 amino acid protein that has not been previously described. It has been localized to chromosome 8, region 8q21.1-23. PMID- 2893505 TI - Present nosography of lymphoproliferative disorders. AB - The present nosography of lymphoproliferative disorders is continuously in progression. Until now, a number of data regarding cytomorphological, cytochemical, immunological and molecular biological findings demonstrated importance in diagnostic and prognostic evaluation. PMID- 2893506 TI - Interleukin-2 receptor-inducing factor(s) in adult T cell leukemia. AB - The expression of the interleukin-2 receptor (IL-2-R) is regulated by transcriptional and post-transcriptional mechanisms. IL-2-R gene expression is induced by pharmacological agents including calcium ions, phorbol esters such as phorbol myristate acetate (PMA) and forskolin (FK), a direct activator of adenylate cyclase. HTLV-I(+) leukemic T cells and T cell lines from patients with adult T cell leukemia (ATL) continuously expressed IL-2-R without production of IL-2. However, there was no abnormality of the structural gene for IL-2-R in these cell lines as well as in fresh leukemic cells of ATL. We have detected that many HTLV-I(+) T4(+) T cell lines constitutively produce a non-IL-2 lymphokine named ATL-derived factor (ADF), which induced the expression of the high-affinity IL-2-R on a variety of cells including HTLV-I(+) T cells, myeloid leukemia cells and YT cells. IL-2-R-inducing agents such as ADF and FK were shown to induce elevation of the mRNA levels for IL-2-R through transcriptional enhancement of the IL-2-R gene. The possible involvement of IL-2-R-inducing cytokines in the physiological lymphocyte activation and the leukemogenesis in ATL and other T cell leukemias is discussed. PMID- 2893507 TI - The effects of alpha adrenergic blockade on central haemodynamics and regional blood flows during positive pressure ventilation. An experimental study in the pig. AB - The effects of alpha receptor blockade on cardiac output distribution in pigs were studied. Recordings were made during spontaneous breathing (SB), during ventilator treatment with 8 Pa positive end-expiratory pressure (8 PEEP), after alpha blockade during SB (SB-alpha) and at 8 PEEP (8 PEEP-alpha). The microsphere method was used for blood flow determinations. The animals received either 5 ml.kg-1.h-1 (Group A) or 10 ml.kg-1.h-1 (Group B) of fluids. In Group A on SB alpha, CO was maintained due to tachycardia but mean arterial pressure (MAP) decreased, renal blood flow and urine production decreased. At 8 PEEP-alpha, CO decreased despite increased heart rate (HR), MAP decreased alarmingly, renal blood flow decreased, urine production ceased and cerebral blood flow decreased, reflecting failing autoregulation. In Group B, CO increased during SB-alpha, SVR decreased, myocardial blood flow increased and organ blood flows were otherwise unchanged. At 8 PEEP-alpha, MAP, SVR, renal, pancreatic and splenic blood flows decreased in Group B. Gastric, intestinal and muscular blood flows were unchanged at 8 PEEP-alpha in Group B which is interpreted as an effect of the alpha blockade. In both groups peripheral arterio-venous shunting increased after alpha blockade. PMID- 2893508 TI - Immunocytochemical studies on thyroid parafollicular cells in postnatal development of the rat. AB - Studies were performed on Wistar strain rats aged 1-720 days. Immunocytochemical reactions were used to detect calcitonin, somatostatin, calcitonin gene-related peptide (CGRP), cholecystokinin, serotonin, neuron-specific enolase (NSE), secretory protein-I, chromogranin and Ca-binding protein. In the parafollicular cells of the rat, the presence of calcitonin, somatostatin, CGRP, NSE and secretory protein-I could be demonstrated. The number of parafollicular cells increased with the age of animals, and the increase was particularly pronounced in the early postnatal period and after the first year of age. The number of somatostatin-immunoreactive cells decreased after birth and increased again after the first year of age. The number of calcitonin-immunoreactive cells increased in the early postnatal period independently of the increase in parafollicular cell number, forming frequently tumor-like outgrowths in 2-year-old animals. A small proportion of these outgrowths contained no calcitonin even if they did contain somatostatin, CGRP and NSE immunoreactivity. Evident changes in immunoreactivity in the first days after birth may reflect the sudden change in environment and may be associated with growth and differentiation. In any period of life, CGRP- and NSE-immunoreactive cells have constituted the most numerous groups and, therefore, the respective antigens seem to represent the most suitable markers of parafollicular cells in the rat. PMID- 2893509 TI - Ocular polyarteritis nodosa. Report of a case. AB - A patient with bilateral amaurosis as a complication to polyarteritis nodosa is presented. He developed affection of the central retinal arteries and the arteries supplying the optic discs followed by retinal and optic atrophy. After one month no vessels could be observed neither in the retinae nor at the optic discs. The importance of early diagnosis and aggressive immunosuppressive treatment is stressed. PMID- 2893510 TI - Development of drug tachyphylaxis in asthmatic patients treated with beta adrenergic drugs. AB - The development of drug tolerance in two groups of asthmatics treated with beta adrenergic bronchodilators was studied by respiratory function methods. During one-year treatment with conventional therapeutic doses of selective beta-2 receptor stimulant aerosols, none of the patients showed subsensitivity to the bronchodilatory effect of terbutaline. Dose-response curves were plotted upon the inhalation of salbutamol in two-week intervals in patients treated with betamimetics. There was no decrease in the airways beta-adrenergic receptor function as compared to the untreated control group. The results show that prolonged treatment with therapeutic doses of inhaled beta-adrenergic bronchodilators does not result in drug tachyphylaxis, which is in accord with the clinical experience that there is no loss of effect of the preparations during their continuous administration. PMID- 2893511 TI - [The search for compounds with dopaminergic action. V. Synthesis of piribedil analogs]. PMID- 2893512 TI - Tardive dyskinesia in neuroleptic medicated mentally handicapped subjects. AB - Sixty-seven neuroleptic medicated mentally handicapped subjects in a hospital were rated on two occasions for abnormal involuntary movements on three scales: Abnormal Involuntary Movements (AIMS), Rockland and Parkinsonism scales, with 6 months between each assessment. Inter-rater and test-retest reliabilities were high. The data from the second assessment was analyzed. Prevalence of tardive dyskinesia (TD) was 21% on AIMS, 42% on the Rockland scale; 60% had parkinsonism. Multiple stepwise regression analysis revealed that age, sex, current neuroleptic and anticholinergic dose, antiepileptic medication, psychosis, cumulative anticholinergic dose were not significant predictors of TD as determined by AIMS. Parkinsonism and cumulative neuroleptic dose were significant predictors of and correlated positively with AIMS score. TD subjects formed 35% of the parkinsonian group. Overt brain damage was not a significant predictor of AIMS score and the difference between the neuroleptic medicated and neuroleptic free group on AIMS scores was highly significant. PMID- 2893513 TI - Tardive dyskinesia in schizophrenics. Prevalence, distribution and relationship to neurological "soft" signs in Nigerian patients. AB - The prevalence of tardive dyskinesia (TD) in 70 Nigerian schizophrenics was 37%. Age was related to the presence of TD in males but not in females. Significantly more females had TD in the lower extremities. Comparison of patients with TD and those without revealed no significant differences with regard to the presence of neurological "soft" signs. PMID- 2893514 TI - Neuroleptic treatment and other factors modifying cancer risk in schizophrenic patients. PMID- 2893516 TI - Neurochemical characterization of excitatory amino acid receptors in hippocampus. PMID- 2893515 TI - [Treatment of tardive dyskinesia induced by neuroleptics]. PMID- 2893517 TI - Effects of acidic dipeptides on aminoacidergic neurotransmission in the brain. PMID- 2893518 TI - Localization of neuroactive substances in the hypothalamus with special reference to coexistence of messenger molecules. PMID- 2893519 TI - Decidual luteotropin secretion and action: its role in pregnancy maintenance in the rat. AB - Studies of rat decidual luteotropin production and action have revealed that decidual mRNA directs the synthesis of a 28,000 MW protein in a cell-free system which binds to prolactin receptors in luteal cells and appears to represent a prohormone for decidual luteotropin. Hybridization studies indicate that although rat decidual and prolactin-like placental hormones bind to prolactin receptors, they possess little homology to other members of the prolactin family. In addition, results of this investigation have revealed a possible physiological relationship between the mesometrial and the antimesometrial cells of the decidual tissue. The large antimesometrial cells produce decidual luteotropin in which secretion and/or synthesis is inhibited by the neighboring mesometrial cells. Since mesometrial cells possess binding sites for decidual luteotropin, it is possible that decidual luteotropin acts on the mesometrial cell to affect the formation of its own inhibitor. Mesometrial cells are rich in glycogen, whose synthesis is stimulated by prolactin-like hormones in other tissues. Therefore, decidual luteotropin may also act on these cells to enhance glycogen formation. In summary, decidual luteotropin appears to have at least two sites of action- the luteal cell, where it can substitute for prolactin in maintaining progesterone production, and the mesometrial cell, where its role remains to be investigated. PMID- 2893520 TI - Further studies on depolarization release coupling in squid giant synapse. PMID- 2893521 TI - A model of the light dependent regulation of retinal rod phosphodiesterase, guanylate cyclase and the cation flux. PMID- 2893522 TI - Synapsin I, a phosphoprotein associated with synaptic vesicles: possible role in regulation of neurotransmitter release. AB - The data presented here provide evidence that the study of neuronal phosphoproteins can lead to the identification of previously unknown proteins and that these proteins may play important roles in neuronal communication. Specifically, in the case of synapsin I, direct evidence has been obtained that this phosphoprotein is involved in regulating neurotransmitter release. A tentative explanation of the results obtained in the micro-injection studies is as follows: synapsin I, in the dephosphostate, is bound to the cytoplasmic surface of synaptic vesicles and inhibits the ability of the vesicle to interact with the plasma membrane; increases in intracellular calcium activate calmodulin kinase II which in turn phosphorylates synapsin I and the phosphorylated synapsin I dissociates from the synaptic vesicle thus removing a constraint on the release of neurotransmitter. Clearly, more studies need to be done to rigorously test this hypothesis. Nevertheless these studies of synapsin I suggest that the study of previously unknown phosphoproteins will lead to the elucidation of previously unknown regulatory processes in neurons. PMID- 2893523 TI - A possible second messenger system for the production of long-term changes in synapses. PMID- 2893524 TI - Altered reactivity of the rat adrenal medulla following periods of chronic stress. PMID- 2893525 TI - Interactions of the alkyl-ether-phospholipid, platelet activating factor (PAF) with platelets, neural cells, and the psychotropic drugs triazolobenzodiazepines. AB - PAF-acether, a naturally occurring phospholipid, is a potent activator of various biological processes, including platelet aggregation. The mechanisms of action of PAF are largely unknown. We have found that the psychotropic triazolobenzodiazepine drugs, alprazolam and triazolam, potently (IC50 less than 1 microM) inhibit PAF-induced shape change, aggregation and secretion of human platelets. These effects are specific for PAF-activation, since the responses of human platelets to other agonists (ADP, thrombin, epinephrine, collagen, arachidonate and the Ca++ ionophore, A23187) are not inhibited by these triazolobenzodiazepines. The action of triazolobenzodiazepines on PAF-induced platelet function has clinical relevance, especially in diseases where enhanced platelet aggregability may lead to thrombosis and atherosclerosis. In addition, the ability of triazolobenzodiazepines to inhibit other PAF-mediated cellular responses, such as anaphylactic shock or bronchoconstriction, suggests that these drugs may be useful in preventing several known pathophysiological effects of PAF. The specific antagonism of PAF action by psychotropic drugs also suggests that PAF or PAF-like phospholipids may play a role in neuronal function. This possibility was tested by examining the effects of PAF on neural cells of the clonal line NG108-15, grown in culture in a chemically defined, serum-free medium. Low concentrations of PAF (0.5-2.5 microM) induced neurite extension in NG108-15 cells, whereas higher concentrations (greater than 3 microM) were cytotoxic. Using NG108-15 cells preloaded with aequorin, it was found that PAF causes an increase in intracellular ionized calcium concentration, which is dependent on the presence of extracellular calcium. These results suggest that PAF-induced Ca++ uptake may play a role in neuronal development, and that circulating PAF may contribute to the neuronal degeneration caused by the exposure of neural tissues to blood in situations such as spinal cord injury, trauma, or stroke. PMID- 2893526 TI - [Neurogenic bladder due to the anterior spinal artery syndrome: 2 case reports]. AB - A 43-year-old woman with anterior spinal artery syndrome was admitted with complaints of tetraplegia and urinary retention. Her bladder had capacity of more than 500 ml and was inactive, with low voltage of external urethral sphincter. She was treated with distigmine bromide and intermittent catheterization. 50 days later, urodynamic study showed normal bladder and incomplete coordination of external sphincter. A 78-year-old man had chief complaints of urinary retention and paraplegia. A catheter was left indwell for 6 months. Then he was treated with intermittent catheterization, but urgency incontinence was still observed. We discussed the therapy of neurogenic bladder due to the anterior spinal artery syndrome. PMID- 2893528 TI - Beta-adrenergic blockers in silent myocardial ischemia. AB - Factors contributing to the development of exercise-induced painful ischemia, such as actions of the central nervous system and catecholamines, have been well identified, but the mechanisms by which nonexercise-related silent episodes of ischemia are provoked are unknown. Possible mechanisms receiving much study in recent years are those having the potential to influence the myocardial oxygen supply-demand relation. Beta-adrenergic receptor stimulations, by increasing myocardial oxygen demand through augmentation of heart rate and contractility (beta 1), may mediate responses that cause ischemia or perpetuate ischemic episodes induced by other means. Other receptors (beta 2) may mediate coronary and peripheral vascular constriction, limiting myocardial oxygen supply and further increasing myocardial oxygen demand. Studies have investigated the effect of beta blockade on ischemic episodes in patients with a variety of clinical forms of coronary heart disease. Beta blockade has been shown to reduce the frequency and duration of silent and painful ischemic episodes in patients with effort angina and rest angina. The data suggest that heart rate and perhaps other changes observed with use of beta blockade play an important role in silent ischemia; heart rate at specific times throughout the day, particularly in the late A.M., and the increase in heart rate seen in conjunction with silent ischemic episodes are all decreased with administration of beta blockade. Results of a recent study focusing only on silent ischemia showed that beta-blocker treatment with metoprolol, compared with placebo, significantly reduced total silent ischemic time (frequency and duration of episodes) in all periods examined. PMID- 2893527 TI - Intravenous fenoldopam in heart failure: comparing the hemodynamic effects of dopamine1 receptor agonism with nitroprusside. AB - Dopamine1 receptors mediate hemodynamic effects that may be beneficial in patients with congestive heart failure. We infused the selective dopamine1 receptor agonist, fenoldopam mesylate (SKF 82526 J), to evaluate hemodynamic and neurohumoral changes during continuous intravenous infusion in patients with congestive heart failure and compared them with the effects of nitroprusside, a traditional vasodilator that works by a distinctly different mechanism. In 15 patients with a mean radionuclide ejection fraction of 17%, the agents were infused in a random-ordered, double-blinded, crossover, active drug-controlled protocol after optimal dosing was determined during a titration period. Hemodynamic changes were induced in minutes with both drugs during a mean (+/- standard deviation) infusion dose of 1.45 +/- 1.66 micrograms/kg/min for fenoldopam and 2.99 +/- 1.59 micrograms/kg/min for nitroprusside. At 1 hour, mean blood pressure decreased and cardiac index rose with both drugs, and the effect lasted throughout the 6-hour infusion period. Nitroprusside, but not fenoldopam, reduced right heart filling pressures (including mean pulmonary capillary wedge, mean right atrial, and mean pulmonary artery pressures) during the infusion period. Both drugs caused significant reduction in systemic vascular and pulmonary arteriolar resistances. No significant change occurred in plasma norepinephrine levels. Fenoldopam ameliorates some of the adverse hemodynamic changes that occur during heart failure but does not reduce right heart filling pressures as does nitroprusside. Because of fenoldopam's unique characteristics, it may benefit certain patients with heart failure. PMID- 2893529 TI - International beta-blocker review in acute and postmyocardial infarction. AB - The benefits of beta blockade in acute and postmyocardial infarction are well documented. More than 50 placebo-controlled trials have been performed, involving more than 40,000 patients with short- or long-term follow-up. In long-term follow up studies in approximately 20,000 patients, mortality was reduced by 21% and reinfarction by 24%. When high-risk patients were assessed separately, the reduction in mortality after early intervention was significantly greater than in low-risk patients. The trial medication was withdrawn in approximately 24% and 28% of patients in the placebo and beta-blocker groups, respectively, in the major trials. In addition to reduction of mortality and reinfarction rates, benefits have clearly been demonstrated in prevention of arrhythmias and thromboatherosclerotic complications. Significantly more patients had hypotension and bradycardia with beta-blocker treatment than with placebo; no clear-cut difference between the placebo and beta-blocker groups was found for atrioventricular block or congestive heart failure when patients with these conditions were excluded. In the Stockholm Metoprolol Trial, 3 years of metoprolol treatment in about 300 patients after myocardial infarction prolonged both survival and time spent completely asymptomatic, in an optimal functional state, or both. Patients receiving metoprolol spent less time disabled after serious atherosclerotic complications, including bypass surgery. Long-term beta blockade after myocardial infarction reduces mortality and morbidity in 80% of patients by 21% and 24%, respectively, but causes adverse reactions in approximately 10%. With proper selection of patients and the type and dose of beta blocker, survival without atherosclerotic complications or adverse effects can be prolonged. PMID- 2893530 TI - A symposium: Hypertension into the nineties. September 6, 1986, Heidelberg, FRG. PMID- 2893532 TI - Celiprolol and the heart. AB - The introduction of beta-adrenoceptor antagonists was a major advance in the treatment of hypertension and coronary artery disease. However, nonselective beta blockade carries distinct circulatory disadvantages, which accounts for the search for an "ideal" beta-blocking drug for use in this extensive therapeutic field. It is possible to define the desirable cardiodynamic profile of a beta blocking drug. How far does celiprolol meet this function? What questions should we address in attempting to evaluate the effects of celiprolol on the heart? In contrast to propranolol, in the normal heart, celiprolol does not depress left ventricular pumping function. There is little information on the effects of celiprolol on left ventricular function in the hypertensive patient. However, we now know that most patients with hypertension already have advancing coronary artery disease. It is reasonable, therefore, to examine the effects of celiprolol on left ventricular function in patients with coronary disease because these can not only be used to evaluate the possible efficacy of the drug in patients with angina pectoris, but also to extrapolate to their clinical effectiveness in most patients with hypertension. Celiprolol does not depress left ventricular pumping function at rest or during exercise, in contrast to other beta-adrenoceptor antagonists that reduce both heart rate and left ventricular activity. Moreover, celiprolol possesses anti-ischemic properties equivalent to those of atenolol. It does not appear to aggravate the atherogenic profile of the lipids as much as some other cardioselective beta-blocking drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893531 TI - Antihypertensive therapy with celiprolol: a new cardioselective beta blocker. AB - Celiprolol is a new generation beta blocker with a novel profile of activity that includes a high degree of cardioselectivity, partial beta 2-agonist activity, and possibly a degree of direct peripheral vasodilation. The drug is hydrophilic, with fewer cardiodepressant effects than other beta antagonists. These ancillary properties may make celiprolol a more suitable beta blocker for use in a broader range of hypertensive patients than conventional agents, and additional work is ongoing in patients with obstructive airways disease, peripheral vascular disorders and those with impaired cardiac function to substantiate and extend current findings. PMID- 2893533 TI - Atenolol and celiprolol for stable angina pectoris. AB - Once-daily atenolol and celiprolol were compared in a placebo-controlled crossover study of 16 patients with stable angina pectoris. Atenolol and celiprolol equally and significantly reduced frequency of angina and electrocardiographic evidence of cardiac ischemia. Celiprolol, however, produced less suppression of the double product at 1 mm of ST-segment depression than atenolol, suggesting that actions other than reduction of heart rate may contribute to its antianginal efficacy. PMID- 2893534 TI - Effects of celiprolol on the bronchial reactivity in asthma. AB - In 10 patients with bronchial asthma but normal ventilatory function, celiprolol, a cardioselective beta-adrenoreceptor antagonist, did not significantly affect forced expiratory volume in 1 second (FEV1) or airways resistance (Raw). In contrast, metoprolol substantially reduced FEV1 and increased Raw. In addition, compared with metoprolol, celiprolol induced a greater recovery of FEV1 and Raw after methacholine-induced bronchoconstriction. PMID- 2893535 TI - Qualities of an ideal beta-adrenoceptor antagonist and comparison of existing agents with a new cardioselective hydrophilic vasodilator beta-adrenoceptor antagonist, celiprolol. AB - Beta-adrenoceptor blockade is established therapy for cardiovascular conditions including hypertension and angina pectoris. The important qualities of a beta adrenoceptor antagonist relate to cardioselectivity, hydrophilicity, peripheral vasodilation, ideal pharmacokinetics and maintenance of the quality of life. Celiprolol, with its known cardioselectivity, hydrophilicity and peripheral vasodilator capacity, measures well by several of these criteria; more data on pharmacokinetics are required. Further testing is indicated, particularly in relation to effects on epinephrine-induced hypokalemia, blood lipid profiles, clinical vasodilatory properties and effects on the quality of life, especially in geriatric patients. PMID- 2893536 TI - Distribution of somatostatinlike immunoreactivity in the brain of the little brown bat (Myotis lucifugus). AB - The distribution of somatostatinlike immunoreactive (SLI) perikarya, axons, and terminals was mapped in subcortical areas of the brain of the little brown bat, Myotis lucifugus, using light microscopic immunocytochemistry. A preponderance of immunoreactivity was localized in reticular, limbic, and hypothalamic areas including: 1) in the forebrain: the bed nucleus of the stria terminalis; lateral preoptic, dorsal, anterior, lateral and posterior hypothalamic areas; amygdaloid, periventricular, arcuate, supraoptic, suprachiasmatic, ventromedial, dorsomedial, paraventricular, lateral and medial mammillary, and lateral septal nuclei; the nucleus of the diagonal band of Broca and nucleus accumbens septi; 2) in the midbrain: the periaqueductal gray, interpeduncular, dorsal and ventral tegmental, pretectal, and Edinger-Westphal nuclei; and 3) in the hindbrain: the superior central and parabrachial nuclei, nucleus incertus, locus coeruleus, and nucleus reticularis gigantocellularis. Other areas containing SLI included the striatum (caudate nucleus and putamen), zona incerta, infundibulum, supramammillary and premammillary nuclei, medial and dorsal lateral geniculate nuclei, entopeduncular nucleus, lateral habenular nucleus, central medial thalamic nucleus, central tegmental field, linear and dorsal raphe nuclei, nucleus of Darkschewitsch, superior and inferior colliculi, nucleus ruber, substantia nigra, mesencephalic nucleus of V, inferior olivary nucleus, inferior central nucleus, nucleus prepositus, and deep cerebellar nuclei. While these results were similar in some respects to those previously reported in rodents, they also provided interesting contrasts. PMID- 2893537 TI - Type-specific efficacy of acellular pertussis vaccine. AB - Two types of acellular pertussis vaccine have been used in Japan since their introduction in 1981. They are different in their antigen content and immunogenicity. To assess the type-specific efficacy of acellular pertussis vaccine commercially available in Japan, 442 households of patients with pertussis were surveyed from 1981 to 1987. The secondary attack rates in children 2 through 8 years of age were 61.3% (46/75) in unimmunized children, 7.5% (4/53) in children fully immunized by the filamentous hemagglutinin predominant type acellular pertussis vaccine, 14.3% (1/7) in children fully immunized by the pertussis toxin-filamentous hemagglutinin type vaccine, and 13.5% (7/52) in children given whole-cell pertussis vaccine. The estimated efficacy was 87.7% for the filamentous hemagglutinin predominant type vaccine and 76.7% for the pertussis toxin-filamentous hemagglutinin type vaccine in children aged 2 through 8 years. Both types of acellular pertussis vaccine were similarly effective, without any statistically significant differences, and their efficacy was not different from that of whole-cell vaccines. This survey also indicated that adults are a major source of infection, with a high secondary attack rate of 7.8%. PMID- 2893538 TI - Diverticulitis in the multiple endocrine neoplasia type II B syndrome. AB - Diffuse ganglioneuromatosis of the entire alimentary tract is a characteristic finding in the multiple endocrine neoplasia type II B syndrome. Symptoms and complications of colonic involvement are common. We report a 37-yr-old woman with multiple endocrine neoplasia type II B syndrome and a colovesical fistula complicating sigmoid diverticulitis. PMID- 2893540 TI - A large Clostridium perfringens foodborne outbreak with an unusual attack rate pattern. AB - On November 7, 1985, a Clostridium perfringens gastroenteritis outbreak occurred in approximately 44% of the 1,362 employees at a Connecticut factory. Although the same foods were served to all three shifts at an employee banquet on November 6, the attack rate was almost twice as high for those who ate on the day shift (attack rate = 50%) than for those on the evening shift (attack rate = 20%) or night shift (attack rate = 29%). Among employees of the day shift, attack rates were highest for those who ate during the first 30 minutes of the 2.5-hour day shift serving period and decreased throughout the serving period. The one-hour evening shift serving period had a similar trend toward higher attack rates earlier in the serving period. Four main-course foods were significantly associated with illness, and over 95% of the employees had eaten each of them. Stratified analysis indicated that gravy was the responsible food and, furthermore, that the decreasing attack rate pattern within serving periods occurred only for those who ate gravy. The gravy had been prepared 12-24 hours in advance of banquet service. After it was prepared, the gravy was improperly cooled and was reheated shortly before and throughout the serving periods. Persons who ate gravy that had been reheated for the longest period of time had the lowest attack rate, probably because they were exposed to a lower concentration of organisms. This outbreak underscores the need for properly reheating food to prevent C. perfringens gastroenteritis and suggests that analysis of attack rate trends may provide important epidemiologic clues to understanding the causes of foodborne disease outbreaks. PMID- 2893539 TI - Human T-cell lymphotropic virus type I (HTLV-I) seroepidemiology and risk factors in metropolitan Panama. AB - Human T-cell lymphotropic virus type I (HTLV-I) infection and associated hematologic malignancies cluster in Japan, the Caribbean basin, and Central Africa. The authors believe that this study of HTLV-I seroepidemiology in the Republic of Panama is the first detailed analytic study of environmental factors pertaining to HTLV-I infection in representative tropical populations. The study analyzed observational data concerning housing conditions, family composition, and demographic and behavioral attributes as risk factors for HTLV-I infection (HTLV-I antibody). The 745 study subjects were residents of representative households in Panama City and Colon. Overall, 5% of sera had antibody against HTLV-I, detected by enzyme-linked immunosorbent assay and confirmed by competitive binding. Housing conditions, race, and socioeconomic factors were not associated with infection nor did infection cluster in families. Interview of 706 women enrolled in cervical cancer studies documented that female sexual experience (number of marriages or sexual partners) was associated with HTLV-I infection. These findings support the hypothesis that HTLV-I is not transmitted by casual contact but requires exposures involving exchange of bodily fluids. PMID- 2893541 TI - Beta S gene in Sicily is in linkage disequilibrium with the Benin haplotype: implications for gene flow. AB - Hemoglobin beta-like gene cluster haplotypes defined by restriction enzyme polymorphic sites are useful in determining the origin of the beta S gene found in several human populations. We present here evidence that the beta S gene found among Sicilians is associated with the same haplotype observed among sickle cell anemia patients from Central West Africa. In addition, this haplotype is either nonexistent or very rare among normal Sicilian individuals. We conclude that the beta S gene was introduced to Sicily from North Africa and that the gene flow originated in Central West Africa and traveled north through historically well defined trans-Saharan commercial routes. PMID- 2893542 TI - Thrombocytopenic purpura in a carrier of human T-cell leukemia virus type I. AB - Thrombocytopenic purpura developed in a 64-year-old woman seropositive for human T-cell leukemia virus type I (HTLV-I). She had no underlying disorders and HTLV-I is suggested as a possible cause of her thrombocytopenia. PMID- 2893543 TI - Uniparental disomy as a mechanism for human genetic disease. AB - A female with cystic fibrosis and short stature was investigated for molecular or cytogenetic abnormalities that might explain the combined phenotype. Analysis with polymorphic DNA markers indicated that the father did not contribute alleles to the propositus for markers near the CF locus or for centromeric markers on chromosome 7. High-resolution cytogenetic analysis was normal, and the result could not be explained on the basis of nonpaternity or a submicroscopic deletion. All of the data indicate that the propositus inherited two identical copies of maternal sequences for much or all of chromosome 7. The occurrence of uniparental disomy could be explained by models postulating postfertilization error, gamete complementation, monosomic conception with subsequent chromosome gain, or trisomic conception followed by chromosome loss. Uniparental disomy in an individual with a normal chromosome analysis is a novel mechanism for the occurrence of human genetic disease. PMID- 2893544 TI - Trisomy 21 (Down syndrome): studying nondisjunction and meiotic recombination by using cytogenetic and molecular polymorphisms that span chromosome 21. AB - By combining molecular and cytogenetic techniques, we demonstrated the feasibility and desirability of a comprehensive approach to analysis of nondisjunction for chromosome 21. We analyzed the parental origin and stage of meiotic errors resulting in trisomy 21 in each of five families by successfully using cytogenetic heteromorphisms and DNA polymorphisms. The 16 DNA fragments used to detect polymorphisms spanned the length of the long arm and detected recombinational events on nondisjoined chromosomes in both maternal meiosis I and maternal meiosis II errors. The meiotic stage at which errors occurred was determined by sandwiching the centromere between cytogenetic heteromorphisms on 21p and an informative haplotype constructed using two polymorphic DNA probes that map to 21q just below the centromere. This study illustrates the necessity of combining cytogenetic polymorphisms on 21p with DNA polymorphisms spanning 21q to determine (1) the source and stage of meiotic errors that lead to trisomy 21 and (2) whether an association exists between nondisjunction and meiotic recombination. PMID- 2893545 TI - A restriction-fragment-length difference detected by the anonymous probe DXS199 exhibits non-Mendelian inheritance. AB - Anonymous DNA probes were isolated from an X chromosome-enriched flow-sorted library. One of these probes, DXS199, identified a restriction-fragment difference that failed to show Mendelian segregation. All normal females were found to have two AvaII fragments of 6.5 kb and 6.0 kb, whereas all normal males had only the 6.5-kb fragment. DNA from a 49,XXXXY male was found to have both 6.0 and 6.5-kb AvaII fragments, in the same 3:1 ratio as seen in the inactive:active number of X chromosomes. This variant, which reflects a structural difference between active and inactive X chromosomes, is likely to be due to a methylation site on the active X chromosome. PMID- 2893546 TI - A linkage and physical map of chromosome 22, and some applications to gene mapping. AB - A genetic map of human chromosome 22 has been derived from physical assignments and multilocus linkage analysis. It consists of the loci for the immunoglobulin lambda light-chain variable (IGLV) and immunoglobulin lambda light-chain constant (IGLC) regions, myoglobin (MB), the sis proto-oncogene (SIS), and an arbitrary probe (D22S1). The first RFLPs at the loci for SIS, IGLV, and MB are described. The most likely gene order on the basis of multilocus analysis was cen-(IGLV IGLC)-D22S1-MB-SIS. This map provides further evidence for localization of the P1 polymorphism of the P blood group to chromosome 22, close to the SIS locus. Analysis of families segregating recessive congenital methemoglobinemia (RCM), a disease in which the cytochrome b5 reductase is defective, as well as of families with cases of hereditary low levels of cytochrome b5 reductase activity, confirmed that the locus responsible for RCM is on chromosome 22. Biochemical studies had already suggested that mutation at the cytochrome b5 reductase locus (DIA1) is responsible for RCM. We found no evidence of genetic heterogeneity between the families segregating RCM and the families exhibiting cases of low cytochrome b5 reductase activity. Linkage analysis indicated that the most probable location of DIA1 lies between MB and SIS. PMID- 2893548 TI - The ornithine aminotransferase (OAT) locus: analysis of RFLPs in gyrate atrophy. AB - A cDNA probe (HOAT1) for ornithine aminotransferase (OAT) has recently been used to map (1) the structural gene for this enzyme to chromosome 10 and (2) several related DNA sequences to the X chromosome. We have defined six RFLPs for OAT, to explore its possible role in gyrate atrophy (GA) of the choroid and retina, an autosomal recessive genetic disorder associated with a deficiency of OAT activity. The RFLPs, which are detected by noncoding single-copy probes from the OAT gene and by subclones of the HOAT1 cDNA, all map on human chromosome 10, producing an overall level of heterozygosity for the OAT locus of 83%. Using the RFLPs, we have determined that the OAT locus segregates concordantly with GA in one available pedigree. Furthermore, the RFLPs display significant disequilibrium with GA, providing genetic evidence implicating a defect in the OAT structural gene as the cause of this disorder. The RFLPs for OAT are potentially applicable to prenatal diagnosis and carrier detection in families with a previous history of GA. They will also allow identification of specific haplotypes associated with GA chromosomes, as a guide for more detailed molecular-genetic investigations of the mutations underlying the disorder. PMID- 2893547 TI - Chromosomal localization of the human proenkephalin and prodynorphin genes. AB - DNA probes derived from rat and human proenkephalin and prodynorphin genes have been used to localize these two opiate neuropeptide genes on human chromosomes. Hybridization of probes to Southern blots made with DNAs from a rodent-human somatic-cell hybrid panel indicates localization of proenkephalin to human chromosome 8 and of prodynorphin to human chromosome 20. In situ hybridization to metaphase chromosomes confirms these assignments and indicates regional localizations of proenkephalin to 8q23-q24 and of prodynorphin to 20p12-pter. A human genomic prodynorphin clone reveals a frequent two-allele TaqI polymorphism. PMID- 2893550 TI - Effect of a two-day stop-order policy on benzodiazepine prescribing. PMID- 2893549 TI - Genetic mapping of the Xq27-q28 region: new RFLP markers useful for diagnostic applications in fragile-X and hemophilia-B families. AB - We have characterized and genetically mapped new polymorphic DNA markers in the q27-q28 region of the X chromosome. New informative RFLPs have been found for DXS105, DXS115, and DXS152. In particular, heterozygosity at the DXS105 locus has been increased from 25% to 52%. We have shown that DXS105 and DXS152 are contained within a 40-kb region. A multipoint linkage analysis was performed in fragile-X families and in large normal families from the Centre d'Etudes du Polymorphisme Humain (CEPH). This has allowed us to establish the order centromere-DXS144-DXS51-DXS102-F9-DXS105-FRAX A-(F8, DXS15, DXS52, DXS115). DXS102 is close to the hemophilia-B locus (z[theta] = 13.6 at theta = .02) and might thus be used as an alternative probe for diagnosis in Hemophila-B families not informative for intragenic RFLPs. DXS105 is 8% recombination closer to the fragile-X locus than F9 (z[theta] = 14.6 at theta = .08 for the F9-DXS105 linkage) and should thus be a better marker for analysis of fragile-X families. However, the DXS105 locus appears to be still loosely linked to the fragile-X locus in some families. The multipoint estimation for recombination between DXS105 and FRAXA is .16 in our set of data. Our data indicate that the region responsible for the heterogeneity in recombination between F9 and the fragile-X locus is within the DXS105-FRAXA interval. PMID- 2893551 TI - Systematic dyskinesia examination of profoundly mentally retarded persons: cooperation and assessment. AB - Performance of 344 institutionalized mentally retarded adults was measured to assess the applicability of the Dyskinesia Identification System Condensed User Scale. A larger proportion of profoundly retarded persons cooperated with Dyskinesia Identification examination procedures than has previously been found. Performance deficits were observed on activation tasks (APA, 1979) that precede assessment of lingual abnormal involuntary movements. Intelligence quotients, neuroleptic dosage, gender, and ambulatory and visual impairments were associated with performance of activation tasks. Results suggest the difficulty of implementing standardized tardive dyskinesia assessments and that client behavior problems may threaten the valid assessment of this disorder among institutionalized profoundly retarded persons. PMID- 2893552 TI - Beta-adrenergic-induced surfactant synthesis, secretion, and reutilization in fetal rabbit lung and isolated differentiating type II alveolar cells. AB - In vivo and in vitro approaches were used to examine the role of beta-adrenergic agonists in the regulation of surfactant synthesis and secretion in the lung. Rabbit fetuses of either 28 or 30 gestational days were treated with isoxsuprine. Fetuses from half of the does in each group were removed and allowed to breathe for 30 minutes. The others were left in utero. Intracellular and extracellular surfactant pools were isolated. Breathing increased secreted surfactant. On the twenty-eighth day without breathing, isoxsuprine treatment increased secretion of surfactant. The reverse effect was noted in the group that received the drug and also breathed. In contrast, on the thirtieth day, the drug inhibited surfactant release in those fetuses that did not breathe. In in vitro studies, undifferentiated type II alveolar cells were isolated and stimulated to differentiate. Subsequent exposure to isoxsuprine (5 or 10 mumol/L) stimulated both the synthesis and secretion of radiolabeled disaturated phosphatidylcholine. Concurrent incubation of those cells exposed to 10 mumol/L isoxsuprine with either unsaturated or disaturated phosphatidylcholine that was carbon 14 labeled showed a strong preference for incorporation of the latter phospholipid into total cellular phosphatidylcholine. These results suggest that beta-adrenergics may inhibit as well as stimulate secretion of surfactant by type II alveolar cells and that these cells may reincorporate secreted disaturated phospholipid. PMID- 2893553 TI - Antigens of Entamoeba histolytica recognized by immune sera from liver abscess patients. AB - Immune sera from 11 patients cured of amebic liver abscess was used to identify antigens of Entamoeba histolytica. Strain HM1-IMSS, among the most virulent in axenic culture, was used. The 37 and 90 Kd antigens were surface glycoproteins as indicated by lactoperoxidase iodination and by Concanavalin A blotting; the 59 Kd antigen was a mannose containing glycoprotein that did not appear to be on the cell surface. Western blots of 11 different immune sera revealed specific binding of immune IgG to 9 amebic proteins. Most frequently recognized proteins were of molecular weight 37, 59, and 90 Kd. The immunoblot pattern in 5 patients was unchanged for up to 30 months post-treatment for liver abscess. PMID- 2893554 TI - Reversal of neurochemical aberrations after tumor resection in rats. AB - Assessment of biochemical parameters in methylcholanthrene sarcoma-bearing rats 2 days after the onset of anorexia revealed several biochemical aberrations in blood and brain. Plasma levels of glucose were decreased and lactate concentrations were increased. The plasma and brain amino acid profiles were also greatly altered in these rats, characterized by increased brain concentrations of glutamine and large neutral amino acids. Analysis of regional neurotransmitter and metabolite levels by high-performance liquid chromatography suggested increases in the neuronal activity of dopamine and serotonin in each brain region examined. Surgical removal of the tumors in another group of anorectic tumor bearing rats was followed by the return of normal feeding within 6 days. Associated with the normalization of food intake was the reversal of these biochemical aberrations in blood and brain. It is hypothesized that the utilization of glutamine and excretion of ammonia by tumor tissue is the precursor of these alterations in brain amino acids and neurotransmitters, which may be causing anorexia. PMID- 2893556 TI - Treatment of pancreatic cutaneous fistulas with a somatostatin analog. AB - Five pancreatic cutaneous fistulas were treated by subcutaneous administration of a long-acting synthetic analog of somatostatin, SMS 201-995. Patients included four men and one woman who ranged in age from 52 to 77 years. The fistulas developed after drainage of a pancreatic abscess, biopsy of a pancreatic mass, splenectomies for idiopathic thrombocytopenic purpura and Felty's syndrome, and operative trauma, respectively. Fistula output consisted of 1,000 ml/day of amylase- and lipase-rich fluid in the patient with a pancreatic biopsy. The other four patients had low-output fistulas (100 to 250 ml/day) that had been draining for 1 to 12 months. Direct communication with the pancreatic duct was demonstrated by endoscopic retrograde cholangiopancreatography, sinography, or both in four of the five patients. Fistula output decreased from 340 +/- 376 ml/day to 63 +/- 36 ml/day on the first day of therapy with two daily doses of 0.05 mg SMS 201-995 (p less than 0.03) and to 13 +/- 19 ml/day on the seventh day of therapy (p less than 0.03). Two patients had prompt closure of their fistulas and one closed in 3 months. One patient with chronic pancreatitis and a duct stricture and one patient with recurring infection did not achieve permanent fistula closure with SMS 201-995. Because of its safety, ease of administration, and efficacy in decreasing fistula output, we believe somatostatin analog therapy is beneficial in hastening closure of pancreatic fistulas. PMID- 2893555 TI - Inhibition of growth of two human pancreatic adenocarcinomas in vivo by somatostatin analog SMS 201-995. AB - Somatostatin inhibits hormone secretion from gastrointestinal endocrine tumors. The purpose of this study was to determine whether SMS 201-995, a long-acting analog, would inhibit the growth of pancreatic adenocarcinomas. Two human pancreatic cancers grown in nude mice were studied: SKI, which has cholecystokinin receptors, and CAV, which does not. Tumors were implanted in groups of six mice each. Treatment groups received SMS 201-995 (100 micrograms/kg three times daily) by intraperitoneal injections and control animals received saline solution. Tumor area was measured twice weekly. After 7 weeks, the tumors and mouse pancreases were excised, weighed, and analyzed for protein and RNA and DNA content. In a second set of experiments, treatment was begun 21 days after transplantation. Mean body weights between groups were not different in any experiment. With treatment beginning on the day of transplantation, the tumor areas of SKI and CAV cancers were reduced by the third and fifth weeks of treatment, respectively. Tumor doubling times were prolonged with treatment in both SKI tumors (5 days) and CAV tumors (6 days). In the SKI treatment groups, tumor weight (52 percent), RNA content (72 percent), and DNA content (60 percent) were decreased at sacrifice compared with those of the control groups. In the CAV treatment group, the mean tumor weight (55 percent) and protein (48 percent), RNA (67 percent) and DNA contents (60 percent) were decreased compared with the CAV control group. Tumor growth of SKI and CAV cancers was also inhibited when treatment was delayed 21 days after transplantation. We conclude that these effects are not mediated by inhibition of cholecystokinin, as seen by similar inhibitory effects on both tumors. Treatment with SMS 201-995 may be an effective hormonal therapy in patients with pancreatic cancers. PMID- 2893557 TI - Postprandial neurohormonal control of gastric emptying. AB - The delay in gastric emptying after a meal is thought to result from nutrient distention-induced release of peptides and neurotransmitters in the gut. The potential contribution of the brain and central neuropeptides to the postprandial regulation of gastric emptying has not been studied adequately. The purpose of this study was twofold: to examine the relative importance and pure central stimulation (sham feeding) or pure peripheral stimulation (duodenal feeding) on gastric emptying, and to determine whether relevant neuropeptides act in the brain to slow gastric emptying of a meal. Six mongrel dogs were prepared with esophageal fistulas, gastric fistulas, duodenal fistulas, and chronic lateral cerebroventricular guides. Gastric emptying of a 300 ml saline solution meal was measured by a phenol red dye dilution technique. Sham feeding of a blenderized meal through the esophageal fistula was used as a central cephalic stimulus. Intraduodenal oleic acid was used as a peripheral stimulus. Both sham feeding and intraduodenal oleic acid inhibited gastric emptying by 59 +/- 12 percent, 73 +/- 5 percent, respectively. In separate studies, we examined the effect on gastric emptying of a bolus injection into the lateral cerebral ventricle of graded doses of corticotropin-releasing factor (110 to 440 pmol/kg), cholecystokinin (16 to 128 pmol/kg), somatostatin-14 (55 pmol/kg), human calcitonin gene-related peptide (230 pmol/kg), and neuropeptide Y (62 to 250 pmol/kg). These peptides are known to affect satiety, gastric emptying, and gastric acid secretion. Of these, only neuropeptide Y and cholecystokinin had an effect on gastric emptying when administered into the lateral cerebral ventricle. Neuropeptide Y inhibited emptying by 28 +/- 8 percent and cholecystokinin accelerated emptying by 32 +/- 12 percent (p less than 0.05). Sham feeding inhibits gastric emptying to a similar degree as intraduodenal feeding, and of the neuropeptides tested, only neuropeptide Y inhibited gastric emptying when given into the brain. The central release of neuropeptides such as neuropeptide Y during a meal may trigger neural pathways that promote postprandial delay in gastric emptying. Central signals may be as important as peripheral signals in the postprandial control of gastric emptying. Further studies are needed to determine the mechanism by which sham feeding inhibits gastric emptying and whether central release of neuropeptide Y is involved. PMID- 2893559 TI - [Total hip prosthesis. A biomechanical concept and its consequences]. PMID- 2893560 TI - Epidural sufentanil versus intramuscular buprenorphine for postoperative analgesia. A double-blind comparative trial. AB - Epidural sufentanil 50 micrograms was compared with intramuscular buprenorphine 0.3 mg for postoperative pain relief. Patients were assigned randomly to one of two treatment groups and received both an intramuscular and epidural injection, one of which was a placebo. Onset of pain relief was faster and quality of analgesia superior during the first 2 hours in the patients who received epidural sufentanil but the duration of analgesia was longer in the buprenorphine group. Cardiovascular variables remained stable in all patients and no respiratory depression was observed. Side effects were more frequent following buprenorphine. PMID- 2893561 TI - Low dose sufentanil pretreatment. Effect on the induction of anaesthesia with thiopentone, methohexitone or midazolam. AB - The effects of pretreatment with varying doses of sufentanil on the subsequent induction of anaesthesia with thiopentone, methohexitone or midazolam were studied in 240 healthy patients. The induction dose requirements for the barbiturates were significantly reduced by sufentanil 5.0 micrograms (methohexitone p less than 0.05, thiopentone p less than 0.01). Excitatory effects following methohexitone were decreased (p less than 0.01) but brief respiratory depression was increased in both cases. Midazolam onset time was reduced, as was the frequency of failed induction, after sufentanil 5.0 micrograms (p less than 0.01). PMID- 2893558 TI - [Pathogenetic treatment with tocolytic drugs of pregnant women with threatened premature labor]. PMID- 2893562 TI - Determination of bromazepam and its urinary metabolites, with a previous hydrolysis reaction, by voltammetric and spectrophotometric techniques. PMID- 2893563 TI - Early ontogeny of catecholaminergic structures in the sheep brain. Immunohistochemical study. AB - The localization of tyrosine hydroxylase was studied in the brain of sheep foetus during early ontogeny using immunohistochemistry. The first immunoreactive neurons appeared very early since they were found on day 30 of pregnancy in the medioventral part of the mesencephalic flexure. The distribution of the different catecholaminergic groups of neurons was similar to the adult's after 75 days of pregnancy. The latest groups to appear was the A12 group. Comparison of the development of the sheep foetus with rodents or primates, more commonly studied, is difficult because of its different development. It seems, however, that catecholaminergic structures appear earlier in sheep and rodents than in human. Considering the early appearance of these transmitters in the central nervous system, their role on brain development has to be studied in the future. PMID- 2893564 TI - Comparison of effects of atracurium and vecuronium in cardiac surgical patients. AB - To compare the cardiovascular effects of intubating doses of atracurium besylate and vecuronium bromide in cardiac surgical patients while utilizing fentanyl anesthesia, 20 patients scheduled for elective coronary artery bypass surgery were randomly assigned to two equal groups in a double-blind fashion. Two minutes after induction of anesthesia, baseline hemodynamic measurements were obtained and either atracurium 0.5 mg/kg (group 1) or vecuronium 0.12 mg/kg (group 2) was administered as an intravenous bolus. Hemodynamic measurements were then repeated 2, 5, and 10 minutes after injection. Atracurium produced a statistically significant decrease in blood pressure at 2 minutes and a statistically significant increase in cardiac output and decrease in systemic vascular resistance at 2, 5, and 10 minutes. Vecuronium produced no statistically significant changes in any hemodynamic variable measured other than a decrease in pulmonary capillary wedge pressure 10 minutes after the drug was administered. The hemodynamic changes seen with atracurium were closely related to changes in serum histamine levels, whereas histamine level did not change after vecuronium. There were no statistically significant differences between the two groups, even though after atracurium statistically significant changes were observed while there were no statistically significant changes associated with vecuronium. It is concluded that when utilizing the above clinical dose range, use of vecuronium may be advantageous over use of atracurium when hemodynamic stability is crucial in the anesthetic management of cardiac surgical patients. PMID- 2893565 TI - [Analgesia on demand after surgery]. PMID- 2893566 TI - [Side effects and complications of epidural analgesia with local anesthetics and narcotic analgesics]. PMID- 2893567 TI - Influence of Bordetella avium infection on association of Escherichia coli with turkey trachea. AB - Four-week-old Bordetella avium-infected and B avium-free turkeys were inoculated intratracheally with a suspension of fimbriated or nonfimbriated Escherichia coli. Numbers of E coli associated with tracheal sections were determined at postinoculation hour (PIH) 1 or 6. Significantly (P less than 0.05) greater numbers of E coli were isolated from the tracheas of B avium-infected turkeys compared with numbers in B avium-free turkeys. In B avium-free turkeys, tracheal associated E coli were 90% less at PIH 6 compared with that at PIH 1. However, in B avium-infected turkeys, numbers of E coli were not affected by postinoculation time. Seemingly, B avium-infected turkeys had reduced capacity to clear E coli from the trachea. PMID- 2893568 TI - Comparison of various anesthetic regimens in the domestic fowl. AB - Three anesthetic agents (equithesin, metomidate, and ketamine) combined with diazepam were tested in the domestic fowl. Laparotomy and thoractomy were possible with the equithesin/diazepam combination, but only laparotomy was possible with the metomidate/diazepam combination. The combination of ketamine/diazepam did not result in the depth of anesthesia required for surgical procedures. Repeated blood pressure and heart rate measurements were recorded by use of a modified noninvasive Doppler technique. Equithesin/diazepam was our combination of choice for long-duration surgical anesthesia. The depth of anesthesia could be modulated by increasing the dose of diazepam. Metomidate/diazepam was useful when short-term anesthesia was required. In contrast to equithesin/diazepam, the metomidate/diazepam combination provided unstable anesthesia of varying depth and duration. Adverse reactions with metomidate indicated caution when using this drug in chickens; the drug also caused marked bradycardia. Ketamine/diazepam combination cannot be recommended as an anesthetic agent for use in chickens. The combination may be useful for minor surgical procedures or treatment, but not for experimental procedures that involve major surgery. Diazepam alone had a slight tranquilizing effect. PMID- 2893569 TI - Morphologic features of Sertoli cells in the intra-abdominal testes of cryptorchid dwarf goats. AB - Light and electron microscopy revealed an age-related progression of alterations of Sertoli cells in the intra-abdominal and scrotal testes of unilaterally cryptorchid West African dwarf goats between the ages of 1 and 30 months. Alterations in the scrotal testis were, however, maturational and included differentiation of Sertoli-to-Sertoli cell junctional specializations, profusion of smooth endoplasmic reticulum, convolution of nuclear profiles, development of vacuolar components of the nucleolus, and an overall change in cell shape in response to proliferation of germinal cells. Corresponding features were observed in Sertoli cells of the contralateral intra-abdominal testis, but the cytoplasmic features were transient because the cells degenerated progressively. Early changes included segregation of the smooth endoplasmic reticulum into compact masses composed of dense, narrow cisternae, dilatation of the rough endoplasmic reticulum cisternae into large, irregular profiles, atrophy of the Golgi complex, and accumulation of lipid droplets and lipofuscin granules. Many of these organelles and inclusions no longer were obvious in Sertoli cells of 12- to 15 month-old goats; rather, intracellular vacuoles and dilated intercellular spaces had become common. In the 24- to 30-month-old goats, Sertoli cells in the intra abdominal testis contained mostly microfilaments and basally located mitochondria with circular cristae in dense matrices. The Sertoli-to-Sertoli cell junctional specializations were structurally intact. These results indicated that, in spite of the unfavorable intra-abdominal environment, Sertoli cells of the intra abdominal testis, before their degeneration, had developed features similar to those of the scrotal testis. PMID- 2893570 TI - Efficacy of amoxicillin trihydrate for the treatment of experimentally induced foot rot in cattle. AB - Twenty holstein heifers were intradermally inoculated in the interdigital skin with a suspension containing Fusobacterium necrophorum and Bacteroides melaninogenicus to induce acute foot rot. Lesions, lameness, and swelling were evaluated during the study, using a subjective scoring system. Rectal temperature, species and number of bacteria isolated, and change in body weight were monitored throughout the study. Ten heifers (treated) were given amoxicillin trihydrate (10 mg/kg of body weight, IM) for 5 days, beginning at the onset of lameness. The remaining 10 heifers (controls) were given physiologic saline solution IM. Treated heifers had less severe lesions and greater weight gain than did control heifers. Rectal temperatures of treated heifers did not differ significantly from those of control heifers. It was concluded that administration of amoxicillin trihydrate early in the course of acute foot rot may reduce the severity of lesions associated with foot rot in cattle. PMID- 2893572 TI - [A case of periarteritis nodosa in a child: discussion of a pure cutaneous form]. PMID- 2893571 TI - [Clinical and virological study of a case of infection with the HIV-LAV 2 virus]. AB - A case of AIDS due to HIV/LAV2 is reported. The patient was a 32 year old man from Guinea-Bissau with no known risk factors. He had brain toxoplasmosis, oral thrush and chronic genital herpes. Investigations for IgG anti-HIV/LAV1' (Elisa, Western Blot, Ripa) were negative. Antibodies to HIV/LAV2 were found and cultures of peripheral blood lymphocytes and cerebro-spinal fluid were positive. HIV/LAV2 seems to be similar to STLV-III (mac), STLV-III (agm), and probably HTLV-IV. PMID- 2893573 TI - [Tissue distribution of 3 beta-blockers in dogs]. PMID- 2893574 TI - Restoration of the foot using the radial forearm flap. AB - Large foot defects unsuitable for reconstruction by local foot flaps are most expediently salvaged with distant free-tissue transfers. Although muscle flaps are preferred for infected wounds, coverage of the clean or acute foot deformity may be better achieved with the innervated radial forearm fasciocutaneous flap. This almost ideal donor site has been used by us for all traumatic foot defects requiring free flaps during the previous year. Our results document that in the 5 available clinical examples, restoration of normal foot contour, durability during ambulation, and an excellent aesthetic appearance were achieved. PMID- 2893575 TI - [Beta-blockers in the treatment of cardiac insufficiency. Pharmacological bases]. AB - Failure of the myocardial pump and poor adjustment of the cardiac output to the oxygen needs of the body, cause sympathetic reflexes (tachycardia and muscular, cutaneous, splanchnic and renal vasoconstriction) which concur to increase arterial blood pressure and cardiac output. This sympathetic hyperstimulation during the evolution of cardiac insufficiency results in many myocardial consequences: increase of the post-charge and cardiac work, depletion of the stock of neuromediator (nor-epinephrine) in the nerve endings of the myocardial sympathetic fibers and decrease of the number of beta-adrenergic receptors of the myocardial cell membranes. It is well known, now, that the "down-regulation" of beta-receptors involves, at least for a short time, a process of internalization of the receptors when subjected to intense stimulation by agonists receptors. A cell enzyme, the "beta-adrenergic receptor kinase" (BARK) causes a phosphorylation of certain sites of the proteins of the beta-receptor when stimulated by agonists. The receptor is then internalized in the cell and fails to be stimulated. It will become functional again and accessible under the membrane under the effect of another enzyme, a phosphatase. These pharmacological findings have led cardiologists to propose a beta-blocking treatment in severe forms (stage IV) of cardiac insufficiency. Biopsies of the myocardium in patients awaiting a heart transplant, have shown recently that under beta-blockers, the number of beta-functional receptors increased and this was interpreted as a response of myocardial cells to the blocking of remaining receptors (equivalent to an up-regulation phenomenon). This mechanism has been advocated to explain the excellent results of the treatment in some patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893576 TI - Ulcerative colitis in Singapore: a clinical study of sixty-one patients. AB - Sixty-one consecutive cases of ulcerative colitis from the Department of Medicine, Singapore General Hospital, over a 16-year period (1971 to 1986) were reviewed. Mean duration of follow-up was 35.9 months (range 2 months to 16 years). Fifty-one (83.6%) cases were diagnosed in the last 8 years. Sex ratio was almost equal (males 30, females 31) and mean age was 38.2 years. All racial groups were affected but a predilection among Indians (21.3%) was observed. At presentation, the disease was mild in 36 (59.0%), moderate in 14 (22.9%) and severe in 11 (18.1%) patients. Fifty-two (85.2%) patients had symptoms of at least one month's duration before presentation. The 3 commonest symptoms were haematochezia (95.1%), diarrhoea (95.1%) and mucoid stools (83.6%). Extraintestinal manifestations of disease such as backache (8.2%), peripheral arthritis (6.5%), iritis (6.5%) and liver disease (1.6%) were uncommon. Severe intestinal complications include toxic megacolon (1.6%), colonic perforation (1.6%) and massive gastrointestinal haemorrhage (1.6%). Haematological and biochemical indices at presentation generally reflected the activity and severity of disease. The disease was limited to the rectum and sigmoid colon in 12 (19.7%) patients, extended up to the splenic flexure in 16 (26.2%), up to the hepatic flexure in another 16 (26.2%) and involved the whole colon in 17 (27.9%). Pseudopolyposis was present in 13 (21.3%) patients. Of 49 patients: (a) 18 (36.7%) had remission and were relapse free subsequently (b) 14 (28.6%) had infrequent relapses (less than 3 x/year) (c) 3 (6.1%) had frequent relapses (greater than 3 x/year) (d) 10 (20.4%) had chronically active disease (e) 4 (8.2%) had a short fulminant course terminating in death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893577 TI - [Contribution of immunocytochemistry to the study of the development of neuroglandular peptidergic systems in the human fetal hypothalamus]. AB - Immunohistochemistry makes possible the in situ detection of neuropeptides in the cell bodies were they are synthesized, in the fibers that carry them, and in endings. Immunohistochemistry appears necessary to identify and map peptidergic neurons and to study their ontogeny. From 1975, we have carried the immunohistochemical study of several hypothalamic neuronal populations in the human fetus: LH-RH (1976), somatostatin (1977), pro-opiocortin (1978), vasopressin and oxytocin (1979), corticoliberin (1982), somatocrinin (1983), and hypothalamic neurons containing an unidentified peptide (1984). Comparative ontogenetical studies have also been performed in rats. PMID- 2893578 TI - ["Push-pull" perfusion technic in neuroendocrinology]. AB - In this article the author reviews the different models of push-pull cannula device used in neuroendocrinology, mainly those applied to the study of neurohormones release from median eminence (ME). At present, three technical details might explain some disagreements resulting from application of push-pull perfusion (PPP) in neuroendocrinology, concerning for instance, the SRIF release: firstly, the tissue damage connected with the diameter of the cannulas utilized (guide and perfusion), secondly, the perfusion flow which can vary from 15 to 40 microliter/min according to the authors, and finally, the means of implanting the cannula in the ME (between 8 days and 1 hour before perfusion). The author compares the values of SRIF, TRH and CRF releases measured by portal cannula with those obtained by PPP. It would seem that the application of a physiological stimulus triggers a response measured in the perfusate whose amplitude as compared to basal levels, is more important than the amplitude measured in portal blood. In conclusion, in despite of its limits--reproductiveness and yield--, at the present time PPP may be considered one of the major methodological tools affording the physiologist optimum conditions for in vivo studies. PMID- 2893579 TI - [A new in vitro model allows use of the same hypothalamus for morphological and functional studies]. AB - A model for combined morphological and functional investigations on the isolated rat mediobasal hypothalamus has been developed. Under these conditions of incubation, the hypothalamic tissue is well preserved, on the basis of photonic and electronic microscopic examinations. This model has been used to study the LHRH system in the rat. LHRH release has been measured in the incubation medium under basal conditions and after KCl-induced depolarisation; the, LHRH has been localized by immunohistochemistry on the hypothalamic fragment. PMID- 2893580 TI - Chromosomal assignment of seven human genomic DNA sequences associated with restriction fragment length polymorphisms. AB - Seven phage clones containing human sequences were picked at random from a human genomic library cloned in Charon 4A. The clones are devoid of repetitive sequences and can be used to recognize restriction fragment length polymorphisms (Feder et al. 1985). The chromosomal locations of the sequences defined by the seven clones have been determined by Southern blotting and DNA hybridization to DNA from human-mouse somatic cell hybrids. The chromosomal assignment of these sequences should increase their value as genetic markers in family studies. PMID- 2893581 TI - Recycling of Bacillus sphaericus 2362 in mosquito larvae: a laboratory study. AB - After ingestion by Culex pipiens and Anopheles stephensi fourth instar larvae, spores of Bacillus sphaericus strain 2362 rapidly germinated inside live mosquito midgut. Bacterial counts and electron microscopic observations on intoxicated larvae revealed that the number of viable spores rapidly decreased during the first 12 h, with a minimum between 12 and 24 h. In cadavers, the number of heat resistant spores quickly increased between the first and second day post-feeding. After one week, the number of spores inside dead larvae reached approximately 20 times the number of ingested spores for both mosquito species (ca. 4 X 10(5) spores/larva). Ultrathin sections of recycled spores showed the presence of a crystalline inclusion identical to that initially present in spores before ingestion. Bioassay on C. pipiens fourth instar larvae showed a similar toxicity between in vivo recycled spores (LC50 = 1.1 +/- 0.3 X 10(5) spores/ml after 24-h exposure) and culture-medium-grown spores of B. sphaericus strain 2362 (LC50 = 1.7 +/- 0.4 X 10(5) spores/ml). PMID- 2893582 TI - Cloning and characterization of the glnA gene of Azospirillum brasilense Sp7. AB - A plasmid which, by complementation, restored a Gln+Nif+ phenotype to the Gln-Nif Azospirillum brasilense mutant 7029, was isolated from a gene bank of total DNA of A. brasilense Sp7 (ATCC 29145) constructed in the broad host range vector pVK100. This plasmid contained the structural gene (glnA) for glutamine synthetase. The glnA gene was mapped by Tn5 insertion and DNA hybridization with a Klebsiella pneumoniae glnA probe. The direction of transcription of glnA was determined. The glnA product was identified as a 50-Kd polypeptide which could be adenylylated in Escherichia coli, and glutamine synthetase activity was characterized in E. coli. Plasmids containing the glnA gene restored glutamine independent growth and a Nif+ phenotype to Gln-Nif- and Gln-Nifc mutants of Azospirillum. PMID- 2893583 TI - Efficiency of plasma exchange in Guillain-Barre syndrome: role of replacement fluids. French Cooperative Group on Plasma Exchange in Guillain-Barre syndrome. AB - The goals of this multicenter controlled trial were: (1) to study the short-term effect of plasma exchange in the Guillain-Barre syndrome when applied alone within 17 days of onset of the disease; and (2) to compare two replacement fluids, diluted albumin and fresh frozen plasma (FFP) with regard to efficacy and morbidity. Two hundred twenty patients were included, 111 in the control group, 109 in the plasma exchange group, 57 of whom were assigned to receive albumin and 52 to receive fresh frozen plasma. Treatment consisted of four plasma exchanges of two plasma volumes each, initiated on the day of randomization and repeated on alternate days. Significant short-term benefits appeared in the group that received plasma exchange as demonstrated by the reduction in the proportion of patients who required assisted ventilation after randomization, and the decrease in time before beginning weaning from ventilator, time to onset of motor recovery, and time to walk with and without assistance. No statistically significant difference was found between the group that received albumin and the group that received fresh frozen plasma. Incidents during exchanges and complications related to the plasma exchange were more frequent in patients who received fresh frozen plasma. Plasma exchange is beneficial in Guillain-Barre syndrome when it is carried out early in the course of the disease. Given its risks and the lack of its clear superiority over albumin, however, we recommend that fresh frozen plasma be abandoned in the treatment of Guillain-Barre syndrome. PMID- 2893585 TI - Radiology of the esophagus. PMID- 2893584 TI - Alanine aminopeptidase and beta 2-microglobulin excretion in patients receiving vancomycin and gentamicin. AB - The effects of vancomycin, gentamicin, and combination vancomycin-gentamicin treatments on alanine aminopeptidase (AAP) and beta 2-microglobulin (beta 2M) elimination in 30 hospitalized patients were assessed and compared with elimination in a control group. Twenty-four-hour urine excretion values for AAP and beta 2M were determined on treatment day 1 and day 5 for patients receiving the three treatment regimens and for the control group. AAP excretion values for the vancomycin-treated group were not found to be statistically different from those of the control group. Both the gentamicin and the vancomycin-gentamicin groups had statistically higher AAP excretion values on treatment day 1 as well as on treatment day 5 when compared with the vancomycin and control groups. AAP excretion on day 5 of treatment was highest for the vancomycin-gentamicin group. Overall, beta 2M elimination was variable in all treatment groups. Although the beta 2M values were elevated as early as day 1 in all treatment groups, they were significantly elevated only in the vancomycin-gentamicin group on day 1 and only in the gentamicin group on day 5 compared with the vancomycin and the control groups. AAP appears to be a sensitive indicator of renal tubular damage. The combination of vancomycin and gentamicin results in greater AAP excretion than does either agent alone. PMID- 2893586 TI - Significance of the alanine aminotransferase reaction in the formation of alpha ketoglutarate in rat liver mitochondria. AB - The total production of alpha-ketoglutarate from glutamate and isocitrate was estimated in isolated rat liver mitochondria. Mitochondrial alanine aminotransferase converts glutamate to alpha-ketoglutarate [A.K. Groen et al. (1982) Eur. J. Biochem. 122, 87-93], thus participating in the net formation of the tricarboxylic acid cycle intermediates from glutamate. The present investigation indicates a significant contribution of the alanine aminotransferase reaction to glutamate oxidation by isolated rat liver mitochondria in the presence of bicarbonate. It amounted to 41-74 and 7-31% of the total utilization of glutamate in States 4 and 3, respectively, in various conditions in vitro, at pyruvate concentrations in the range of 0.1-10 mM. The participation of glutamate in the total production of alpha-ketoglutarate at physiological concentrations of glutamate, citrate, and isocitrate varied in the range of 72-82%. It was calculated that alpha-ketoglutarate formation by the reaction of alanine aminotransferase amounted to 30 and 5% of the total mitochondrial alpha-ketoglutarate production in States 4 and 3, respectively, at physiological concentrations of its precursors and in the presence of 0.5 mM malate and 0.1 mM pyruvate. It constituted 77-97% of the net production of the tricarboxylic acid cycle intermediates from glutamate in rat liver mitochondria. The importance of alpha-ketoglutarate production via the alanine aminotransferase reaction under various physiological conditions is discussed. PMID- 2893587 TI - Specificity of tyrosine protein kinases of the structurally related receptors for insulin and insulin-like growth factor I: Tyr-containing synthetic polymers as specific inhibitors or substrates. AB - The receptors for insulin and insulin-like growth factor (IGF) I are structurally similar transmembrane proteins. Ligand binding to the extracellular domain of the receptor stimulates its cytoplasmic tyrosine protein kinase which phosphorylates its own beta subunit as well as exogenous substrates. It is believed, from several lines of evidence, that tyrosine-specific protein kinases are mediating some or all of the actions of insulin (or IGF-I). In order to gain insights into the substrate specificity of the structurally related insulin and IGF-I receptor kinases, we have studied the action of highly purified receptors isolated from human placental membranes. Present studies using selected tyrosine-containing polymers have revealed: (i) Polymers such as (Y,A,E)n and (Y-A-E)n inhibit beta subunit autophosphorylation and exogenous substrate phosphorylation by autophosphorylated receptors. (ii) Insulin receptor kinase is at least 10 times more sensitive to these inhibitors than IGF-I receptor kinase. (iii) (Y-A-E)n is approximately 8 times more potent an inhibitor than (Y,A,E)n toward both receptors. (iv) While (E4,Y1)n and (E6,A3,Y1)n are good substrates for both receptor kinases, the ratio of phosphate incorporation into the former to the latter is characteristically high (approximately 4) for the IGF-I receptor and low (approximately 1) for the insulin receptor. These results imply that the substrate specificity and enzymatic action of these two receptor kinases are distinct. PMID- 2893588 TI - Pyridine nucleotide oxidation by a plasma membrane fraction from red beet (Beta vulgaris L.) storage tissue. AB - The potential role of pyridine nucleotide oxidation in the energization and/or regulation of membrane transport was examined using sealed plasma membrane vesicles isolated from red beet (Beta vulgaris L.) storage tissue. In this system, pyridine nucleotide oxidation, which was enhanced in the presence of ferricyanide, occurred. In the presence or absence of ferricyanide, the oxidation of NADH was several-fold greater than the oxidation of NADPH, indicating that it was the preferred substrate for oxidation in this system. Ferricyanide reduction coupled to NADH oxidation did not require the transmembrane movement of reducing equivalents since ferricyanide incorporated inside the vesicles could not be reduced by NADH added externally to the vesicles, unless the vesicles were made leaky by the addition of 0.05% (v/v) Triton X-100. Using fluorescent probes for the measurement of transmembrane pH gradients and membrane potentials, it was determined that NADH oxidation did not result in the production of a proton electrochemical gradient or have any effect upon the proton electrochemical gradient produced by the plasma membrane H+-ATPase. The oxidation of NADH in the presence of ferricyanide did result in the acidification of the reaction medium. This acidification was unaffected by the addition of Gramicidin D and stimulated by the addition of 0.05% (v/v) Triton X-100, suggesting a scalar (nonvectorial) production of protons in the oxidation/reduction reaction. The results of this study suggest that the oxidation of pyridine nucleotides by plasma membrane vesicles is not related to energization of transport at the plasma membrane or modulation of the activity of the plasma membrane H+-ATPase. PMID- 2893589 TI - The binding of divalent metal ions to platelet factor XIII modulates its proteolysis by trypsin and thrombin. AB - We investigated the effect of divalent metal ions on the proteolytic cleavage and activation of platelet Factor XIII by thrombin and trypsin. In the absence of metal ions (5 mM EDTA), trypsin and thrombin rapidly degraded platelet Factor XIII (80 kDa) to low-molecular-mass peptides (50-19 kDa) with simultaneous loss of transglutaminase activity. Divalent metal ions protected Factor XIII from proteolytic inactivation with an order of efficacy of Ca2+ greater than Zn2+ greater than Mg2+ greater than Mn2+. Calcium (2 mM) increased by 10- to 1000-fold the trypsin and thrombin concentrations required to degrade Factor XIII to a 19 kDa peptide. Factor XIIIa formed by thrombin in the presence of 5 mM EDTA had one half the specific activity of Factor XIIIa formed in the presence of calcium. Factor XIII was cleaved by trypsin in the presence of 5 mM Ca2+ to a 51 +/- 3-kDa fragment that had 60% of the original Factor XIIIa activity. A similar tryptic peptide formed in the presence of 5 mM EDTA did not have transglutaminase activity. In the presence of 5 mM Mg2+, thrombin cleaved Factor XIII to a major 51 +/- 3-kDa fragment that had 60% of the Factor XIIIa activity. Mn2+ (0.1-5 mM) limited trypsin and thrombin proteolysis. The resulting digest containing a population of Factor XIII fragments (50-14 kDa) expressed 50-60% transglutaminase activity of Factor XIIIa. Factor XIII was fully activated by both trypsin and thrombin in the presence of 5 mM Zn2+, resulting in two fragments of 76 and 72 kDa. We conclude that the binding of divalent metal ions to platelet Factor XIII induces conformational changes in the protein that alter its susceptibility to proteolysis and influence the expression of transglutaminase activity. PMID- 2893590 TI - Directed mutagenesis of the dicyclohexylcarbodiimide-reactive carboxyl residues in beta-subunit of F1-ATPase of Escherichia coli. AB - Previous studies in which dicyclohexylcarbodiimide (DCCD) was used to inactivate F1-ATPase enzymes have suggested that two glutamate residues in the beta-subunit are essential for catalysis. In the Escherichia coli F1-ATPase, these are residues beta-Glu-181 and beta-Glu-192. Oligonucleotide-directed mutagenesis was used to change these residues to beta-Gln-181 and beta-Gln-192. The beta-Gln-181 mutation produced strong impairment of oxidative phosphorylation in vivo and also of ATPase and ATP-driven proton-pumping activities in membranes assayed in vitro. A low level of each activity was detected and an F1-ATPase appeared to be assembled normally on the membranes. Therefore, it is suggested that the carboxyl side chain at residue beta-181 is important, although not absolutely required, for catalysis in both directions on E. coli F1-ATPase. The beta-Gln-192 mutation produced partial inhibition of oxidative phosphorylation in vivo and membrane ATPase activity was reduced by 78%. These results contrast with the complete or near-complete inactivation seen when E. coli F1-ATPase is reacted with DCCD and imply that DCCD-inactivation is attributable more to the attachment of the bulky DCCD molecule than to the derivatization of the carboxyl side chain of residue beta-Glu-192. M. Ohtsubo and colleagues (Biochem. Biophys. Res. Commun. (1987) 146, 705-710) described mutagenesis of the F1-beta-subunit of thermophilic bacterium PS3. Mutations (Glu----Gln) of the residues homologous to Glu-181 and Glu-192 of E. coli F1-beta-subunit both caused total inhibition of ATPase activity. Therefore, there was a marked difference in results obtained when the same residues were modified in the PS3 and E. coli F1-beta-subunits. PMID- 2893591 TI - [Attempted marrow rescue with cryopreserved circulating stem cells following high dose chemotherapy]. AB - Circulating hematopoietic stem cells were collected by three consecutive leukaphereses during post-chemotherapy expansion of the stem cell pool in a 3 year-old boy with advanced and therapy-resistant neuroblastoma. The cells were fractionated by discontinuous Percoll gradient centrifugation, frozen in a programmed freezer and then stored in liquid nitrogen. Following high-dose chemotherapy, the cells were thawed rapidly and re-infused into the patient. Early evidence of marrow recovery was first noted at day 13 and the times required to achieve a granulocyte count of greater than 0.5 x 10(9)/L and a platelet count of greater than 50 x 10(9)/L were 21 days and 30 days, respectively. This new marrow-rescue operation may have potential in cancer therapy as an alternative to bone marrow transplantation and further clinical investigation is warranted. PMID- 2893592 TI - Treatment of the dumping syndrome with the somatostatin analogue SMS 201-995. AB - In six patients suffering from severe early dumping and six patients with late dumping after peptic ulcer surgery, the effect of the somatostatin analogue SMS 201-995 was compared with placebo. In early dumpers subcutaneous administration of 50 micrograms SMS 201-995 prior to meal ingestion induced a strong improvement of dumping symptoms as reflected by a decrease of the Sigstad dumping score from 12 +/- 2 during placebo to 5 +/- 2 (p less than 0.05). Furthermore, the postprandial increase of pulse rate was abolished; maximum pulse rate decreased from 85 +/- 7 beats/min to 67 +/- 7 beats/min (p less than 0.05). SMS 201-995 did not significantly affect postprandial changes in packed cell volume. In late dumpers 50 micrograms SMS 201-995 reduced peak plasma insulin after oral glucose from 173 +/- 16 mU/L during placebo to 35 +/- 9 mU/L during SMS 201-995 (p less than 0.05) and increased individual plasma glucose nadirs from 1.9 +/- 0.3 mmol/L to 7.5 +/- 3.3 mmol/L (p less than 0.01). Both in early and late dumpers SMS 201 995 improved postprandial expiratory breath hydrogen excretion indicating slowing of gastrointestinal hurry. SMS 201-995 is a powerful therapeutic agent for the management of patients suffering from the dumping syndrome after gastric surgery. PMID- 2893593 TI - The effect of somatostatin on experimental intestinal obstruction. AB - The effect of somatostatin (SS-14) was tested in an anesthetized rabbit model of closed-loop ileal obstruction. Experimental groups included (1) immediate treatment (N = 6) receiving SS-14 2,000 pmol X kg-1 X h-1 intravenously (I.V.) beginning at the time of ileal obstruction, (2) delayed treatment (N = 5) receiving SS-14 beginning 6 hours following ileal obstruction, and (3) control (N = 6) receiving only hydration. After 24 hours, all rabbits were killed. Significantly decreased intestinal luminal volume and sodium and potassium output was observed with both immediate and delayed SS-14 treatment when compared to control. Additionally, the gross and microscopic pathologic features of intestinal distension, inflammation, and necrosis seen in control rabbits were absent in rabbits treated with SS-14. The known broad spectrum of physiologic activity of SS-14 on the gastrointestinal tract appeared beneficial in this rabbit model of intestinal obstruction. PMID- 2893594 TI - Production of lactate and tissue plasminogen activator in vitro by seminiferous tubules obtained from adult unilaterally cryptorchid rats. AB - Pieces of seminiferous tubules obtained from adult unilaterally cryptorchid rats were incubated in vitro and the effect of FSH on the secretion of lactate and tissue-plasminogen activator (t-PA) was studied. Tubules from abdominal testes secreted less lactate than scrotal tubules. On the other hand, the basal secretion of t-PA was similar but the FSH-stimulated t-PA secretion was larger from abdominal than from scrotal tubules. These results indicate a more specific dysfunction of the Sertoli cells in cryptorchidism than earlier recognized. PMID- 2893595 TI - Interaction between extracellular magnesium and the passage of calcium through the sarcolemma during depolarization of isolated feline coronary and femoral arteries. AB - The mode of action of Mg2+ on vascular smooth muscle has been examined in isolated feline coronary and femoral arterial segments using a sensitive in vitro method. Potassium (124 mM) was added to feline coronary and femoral arteries incubated in a calcium-free buffer solution containing 10 microM EGTA, and magnesium in various concentrations (1.2, 4.4 or 13.2 mM). Potassium induced during these conditions a small contraction whose magnitude was attenuated by raised concentrations of Mg2+ (4.4 and 13.2 mM). Subsequent cumulative addition of calcium (10(-6)-3 x 10(-3) M) resulted in concentration-dependent contractions. The magnitude of these contractions was magnesium-dependent; the contraction elicited was depressed and a dextral shift of the extracellular calcium concentration-response relation was noted in the presence of increased concentrations of Mg2+ (4.4 and 13.2 mM). In separate experiments performed on potassium-depolarized (124 mM) feline coronary arteries it was noted that magnesium-induced relaxation was not changed by the presence of propranolol (10( 6) M), cimetidine (10(-6) M) or atropine (10(-5) M). In addition, the mechanical removal of the endothelium did not affect the dilator effect of Mg2+, as examined in potassium-depolarized (124 mM) feline femoral arteries. Hence, it may be concluded that Mg2+ may interfere with the passage of extracellular calcium through the sarcolemma, and that the dilator effect of magnesium is not the result of a direct action on beta-adrenoceptors, histamine H2 or cholinergic receptors, or requires the presence of an intact endothelium. PMID- 2893596 TI - Apparent affinity values of beta-adrenergic blockers in a tissue with a mixture of beta-adrenergic receptor subtypes. AB - The affinity (pA2 or pKB) values of 3 different beta-adrenoceptor blocking drugs were determined using the isolated guinea-pig tracheal chain preparation. The pA2 values for each of the beta-adrenoceptor blocking drugs were determined, using respectively isoprenaline and salbutamol as agonists. Neuronal and extraneuronal uptake of agonist were blocked with phenoxybenzamine. With isoprenaline, a nonselective beta-adrenoceptor agonist, the pA2 values for the blocking drugs were unacceptable. Using the beta 2-selective beta-adrenoceptor agonist, salbutamol, under the same conditions, resulted in consistent pA2 values for the nonselective beta-adrenoceptor blocking drug propranolol and some concentrations of the beta 2-selective blocking drug ICI 118.551. pA2 Values for the beta1 selective antagonist atenolol were not consistent for the concentrations used. It is suggested that this is due to the guinea-pig trachea having a mixed beta adrenoceptor population. A mathematical model is presented that shows the influence of a mixed receptor subpopulation on the shift of theoretical agonist concentration-effect curves in the presence of a competitive antagonist. It can be shown that the affinity values of antagonists for a specific receptor subtype are to a greater or lesser degree unreliable, depending upon the selectivity ratios of both the agonist and the antagonist used. PMID- 2893597 TI - Inhibition of cyclo-oxygenase attenuates the metabolic response to endotoxin in humans. AB - Acute infection initiates fever, acute-phase changes, and catabolic responses in the host, resulting in weight loss, hypermetabolism, and accelerated proteolysis. To test the hypothesis that cyclo-oxygenase inhibition might attenuate these responses, we administered Escherichia coli endotoxin intravenously to seven normal volunteers and to seven additional subjects pretreated with a cyclo oxygenase inhibitor (ibuprofen). Control studies were also performed following administration of saline and ibuprofen alone. Vital signs, metabolic rate, and concentrations of pituitary and stress hormones, as well as those of other substrates, were serially measured. Endotoxin administration produced a response similar to an acute illness, with flulike symptoms, fever, tachycardia, increased metabolic rate, and stimulation of stress hormone release. These changes were markedly attenuated by cyclo-oxygenase inhibition. The leukocytosis, hypoferremia, and elevation of the C-reactive protein level induced by endotoxin were unaffected by cyclo-oxygenase inhibition. These data indicate that activation of the cyclooxygenase pathway is necessary to produce many of the metabolic changes observed during critical illness. PMID- 2893598 TI - [The effect of dilevalol in histamine-induced airway constriction in guinea pigs]. PMID- 2893599 TI - [Allergic granulomatosis and angitis: report on a case who died in a fulminant course]. PMID- 2893600 TI - Cerebrospinal fluid somatostatin and neuropeptide Y. Concentrations in aging and in dementia of the Alzheimer type with and without extrapyramidal signs. AB - Cerebrospinal fluid somatostatin and neuropeptide Y concentrations were measured in 26 healthy normal subjects, 27 patients with dementia of the Alzheimer type (DAT), and seven patients with DAT with extrapyramidal signs (EDAT). In healthy normal subjects, there was no significant correlation between age and either somatostatin or neuropeptide Y concentration. However, the concentrations of both peptides correlated significantly with each other. In patients with DAT and EDAT, the concentrations of somatostatin (17.5 +/- 5.0 and 16.4 +/- 5.0 pg/mL, respectively) were significantly reduced relative to age-matched control subjects (23.1 +/- 8.2 pg/mL) but were unrelated to dementia severity and did not change significantly during the progression of the disease. Neuropeptide Y concentrations did not differ significantly between the age-matched control, DAT, and EDAT groups (38.2 +/- 12.8, 37.0 +/- 12.3, and 30.3 +/- 7.8 pg/mL, respectively). These results suggest that in DAT, dysfunction of cortical somatostatin but not neuropeptide Y transmitter systems is reflected by reduced cerebrospinal fluid concentrations. PMID- 2893602 TI - Behavioral indices of habituation and sensitization during exposure to phobic stimuli. PMID- 2893601 TI - A survey of the management of premature labour by Australian obstetricians. AB - A survey of the practices of obstetricians in the management of premature labour was carried out. A questionnaire consisting of 16 clinical problems was drawn up. All Fellows and Members of the RACOG resident in Australia were surveyed by mail and 707 (74.3% of those in active practice) returned completed questionnaires. Results were analysed by State, seniority and practice size. The survey revealed many differences in management even in situations tested by clinical trials (e.g. premature rupture of membranes, use of steroids). There was uncertainty about when to attempt inhibition with tocolytics. Obstetricians had a more pessimistic view concerning neonatal survival than recent published neonatal results indicate. The role of chorioamnionitis seemed undervalued. There were many differences when results were analysed by State and seniority. PMID- 2893603 TI - Characterization of three peptides derived from prosomatostatin [prosomatostatin (1-63)-, -(65-76)- and -(79-92)-peptides] in a human pancreatic tumour. AB - By using only reverse-phase h.p.l.c., three fragments of prosomatostatin were isolated from an extract of a human pancreatic neuroendocrine tumour that produced somatostatin, vasoactive intestinal polypeptide and gastrin-releasing peptide. The amino acid composition of the peptides indicated that they represented prosomatostatin-(1-63)-peptide, prosomatostain-(65-76)-peptide and prosomatostatin-(79-92)-peptide (somatostatin-14). The identity of prosomatostatin-(1-63)-peptide was confirmed by characterization of the products of digestion with Armillaria mellea (honey fungus) proteinase. Partial micro sequencing of prosomatostatin-(1-63)-peptide showed that the Gly24-Ala25 bond of preprosomatostatin was the site of cleavage of the signal peptide. Thus human prosomatostatin is a protein of 92 amino acid residues that is proteolytically cleaved in a pancreatic tumour at the site of a dibasic-residue (arginine-lysine) processing site and at a single-monobasic-residue (arginine) processing site. PMID- 2893604 TI - Cloning of rat brain succinyl-CoA:3-oxoacid CoA-transferase cDNA. Regulation of the mRNA in different rat tissues and during brain development. AB - 3-Oxoacid CoA-transferase, which catalyses the first committed step in the oxidation of ketone bodies, is uniquely regulated in developing rat brain. Changes in 3-oxoacid CoA-transferase activity in rat brain during the postnatal period are due to changes in the relative rate of synthesis of the enzyme. To study the regulation of this enzyme, we identified, with a specific polyclonal rabbit anti-(rat 3-oxoacid CoA-transferase), two positive cDNA clones (approx. 800 bp) in a lambda gtll expression library, constructed from poly(A)+ RNA from brains of 12-day-old rats. One of these clones (lambda CoA3) was subcloned into M13mp18 and subjected to further characterization. Labelled single-stranded probes prepared by primer extension of the M13mp18 recombinant hybridized to a 3.6 kb mRNA. Rat brain mRNA enriched by polysome immunoadsorption for a single protein of size 60 kDa which corresponds to the precursor form of 3-oxoacid CoA transferase was also found to be similarly enriched for the hybridizable 3.6 kb mRNA complementary to lambda CoA3. Affinity-selected antibody to the lambda CoA3 fusion protein inhibited 3-oxoacid CoA-transferase activity present in rat brain mitochondrial extracts. The 3.6 kb mRNA for 3-oxoacid CoA-transferase was present in relative abundance in rat kidney and heart, to a lesser extent in suckling brain and mammary gland and negligible in the liver. The specific mRNA was also found to be 3-fold more abundant in the brain from 12-day-old rats as compared with 18-day-old foetuses and adult rats, corresponding to the enzyme activity and relative rate of synthesis profile during development. These data suggest that 3 oxoacid CoA-transferase enzyme activity is regulated at a pretranslational level. PMID- 2893607 TI - Adenylate cyclase and guanylate cyclase activity in the conduction system of rabbit hearts. AB - In comparison to the working myocytes no remarkable differences in the localization of adenylate cyclase (AC) and guanylate cyclase (GC) were found. The sarcolemmal plasma membrane of the AV node and the Purkinje fibers was the main site of the activity of these two enzymes. GC activity was additionally found at peripheral junctional couplings. Stimulation by hormones and specific activators for both AC and GC was demonstrated with difficulty. The reasons may be more the cytochemical preparation technique than the specificity of the AC and GC in the conducting tissue. PMID- 2893606 TI - Glutamine and ketone-body metabolism in the gut of streptozotocin-diabetic rats. AB - 1. In short- and long-term diabetic rats there is a marked increase in size of both the small intestine and colon, which was accompanied by marked decreases (P less than 0.001) and increases (P less than 0.001) in the arterial concentrations of glutamine and ketone bodies respectively. 2. Portal-drained viscera blood flow increased by approx. 14-37% when expressed as ml/100 g body wt., but was approximately unchanged when expressed as ml/g of small intestine of diabetic rats. 3. Arteriovenous-difference measurements for ketone bodies across the gut were markedly increased in diabetic rats, and the gut extracted ketone bodies at approx. 7 and 60 nmol/min per g of small intestine in control and 42-day-diabetic rats respectively. 4. Glutamine was extracted by the gut of control rats at a rate of 49 nmol/min per g of small intestine, which was diminished by 45, 76 and 86% in 7-, 21- and 42-day-diabetic rats respectively. 5. Colonocytes isolated from 7- or 42-day-diabetic rats showed increased and decreased rates of ketone body and glutamine metabolism respectively, whereas enterocytes of the same animals showed no apparent differences in the rates of acetoacetate utilization as compared with control animals. 6. Prolonged diabetes had no effects on the maximal activities of either glutaminase or ketone-body-utilizing enzymes of colonic tissue preparations. 7. It is concluded that, although the epithelial cells of the small intestine and the colon during streptozotocin-induced diabetes exhibit decreased rates of metabolism of glutamine, such decreases were partially compensated for by enhanced ketone-body utilization by the gut mucosa of diabetic rats. PMID- 2893605 TI - The structure and mechanism of neurotransmitter receptors. Implications for the structure and function of the central nervous system. PMID- 2893608 TI - Metabolism of the tricarboxylic acid cycle intermediates and related amino acids in ischemic guinea pig heart. AB - The changes in the contents of the main tricarboxylic acid cycle intermediates and related amino acids under total ischemia and subsequent reperfusion of isolated guinea pig heart were studied. The decrease in ATP and phosphocreatine during 30 min ischemia was accompanied by alanine formation and approximately stoichiometric glutamate loss. The increase in malate in ischemic myocardium corresponded to the anaplerotic flux aspartate----oxaloacetate----malate. The succinate production was commensurable to alpha-ketoglutarate formation in the alanine aminotransferase reaction. The release of bulk amount of lactate, alanine and succinate into the myocardial effluent was observed during an early phase of the reperfusion using 1H NMR. In contrast to these metabolites, malate release was not observed in the reperfusion. By the 30th min of the reperfusion the decrease in lactate, alanine, malate and succinate tissue contents to the preischemic values was accompanied by the recovery of ATP and phosphocreatine. The results suggest that the formation and the release of succinate and alanine from the heart, complementary to that of lactate, reflect profound disturbances in energy metabolism. PMID- 2893609 TI - Myofibril formation in longterm-cultures of adult rat heart cells. AB - Immunocytochemistry using antibodies against myofibrillar proteins such as heart C-protein and myomesin but also the fluorescence of rhodamine conjugated phalloidin as marker for F-actin structures was employed to study the redifferentiation of cultured adult rat cardiomyocytes. It was demonstrated that freshly isolated rod shaped cells in culture round up before they attach to the substratum, while myofibrillar structures of the cells degenerate. As soon as they attached to the substratum and gradually flattened out, small cross-striated myofibrils reappeared in the central part of the cells. F-actin, in freshly isolated cells present only in the I-band of the myofibrils, extended throughout the cells into the processes in the form of filament cables. In later stages the myofibrillar distribution varied. Smaller myocytes were frequently filled with myofibrils whereas in larger cells with many processes the myofibrils were found either arranged in perinuclear regions or showed a mosaic distribution. Myofibrils appear to be directly aligned with bundles of actin stress fibers, thus further supporting the suggestion that the actin filaments might serve as a scaffold for myofibril formation. PMID- 2893610 TI - The vacuolar proton-ATPase of eukaryotic cells. PMID- 2893611 TI - Modulation of c-myc by transforming growth factor-beta in human colon carcinoma cells. AB - Previous work indicated that transforming growth factor-beta elicits proliferation-inhibitory and differentiation-like effects in the human colon carcinoma cell line MOSER. We report for the first time that the proto-oncogene c myc is repressed in response to transforming growth factor-beta in a human colon carcinoma cell line. We also describe a subline of these cells which are relatively resistant to the transforming growth factor-beta-induced effects on proliferation in monolayer and in soft agarose, but which retain the ability to specifically bind transforming growth factor-beta. Analysis of molecular and cellular alterations in this subline may aid in elucidating the mechanism of action of transforming growth factor-beta. PMID- 2893612 TI - S-oxalylglutathione is a substrate for gamma-glutamyltransferase (GGT). Implications for the role of GGT in cell proliferation. AB - With glycylglycine or water as acceptor, bovine kidney gamma-glutamyltransferase catalyzes reactions of the known mammalian metabolite, S-oxalylglutathione, at rates comparable to those of L-gamma-glutamyl-p-nitroanilide, a known good substrate. N-Oxalyl-cysteinylglycine is the eventual product of the former reaction. Since oxalyl thiolesters are implicated as important cell proliferation inhibitors, it is proposed that this reaction plays a major role in controlling cell proliferation. PMID- 2893613 TI - Alpha-blocker, bunazosinhydrochloride decreases cytosolic Ca++ of cultured rat aortic smooth muscle cells. AB - Effect of alpha-blocker, bunazosinhydrochloride on cytosolic Ca++ concentration of rat aortic smooth muscle cells (SMC) was studied. Marked and sustained decrease in cytosolic Ca++ concentration of SMC was observed following the addition of 10(-7) M bunazosinhydrochloride. Furthermore, 10(-7) M bunazosinhydrochloride completely blocked the phenylephrine induced increase in cytosolic Ca++ of rat aortic SMC. It is of interest that a decrease in cytosolic Ca++ of vascular SMC was caused by alpha-blocker. PMID- 2893614 TI - Structural and functional differences in H+-ATPases with native and reconstituted inhibitor protein. AB - Anti F1 antibodies that react with the alpha and beta subunits of the mitochondrial F0-F1 ATPase complex do not interfere with the natural inhibitor protein-ATPase interaction as revealed by inhibitor peptide titration curves. Submitochondrial particles with endogenous or added bound inhibitor protein show differences in immunoprecipitation. Submitochondrial particles which are partially depleted of inhibitor protein gave the same immunoprecipitation curve as the Mg-ATP particle. Anti F1 antibodies induce differential effects in ATP hydrolysis and ATP-Pi exchange. ATP hydrolysis is stimulated in Mg-ATP particles to 200%, while inhibitor depleted and inhibitor reconstituted particles are inhibited by the presence of the antibodies. ATP-Pi exchange is stimulated in inhibitor reconstituted particles and inhibited in Mg-ATP and inhibitor depleted particles. These results suggest that the inhibitor protein when endogenously bound confers a different conformation to the F1-ATPase than that of the F1 ATPase with added bound inhibitor protein. PMID- 2893615 TI - Altered enzyme profile is possibly related to hepatocarcinogenesis by clofibrate. AB - Sequential analysis of a few biochemical markers was carried out in rat liver exposed to the hypolipidemic drug, clofibrate. A transformation marker, gamma glutamyltranspeptidase (GGT), proliferation markers, polyamines, differentiation markers, arginase and ornithine transaminase (OTA), were chosen for the study. GGT activity was significantly reduced with an increase in glutathione concentration. Polyamine synthesis was markedly elevated 5 h following clofibrate administration. However, chronic exposure evoked only a moderate increase in polyamine profile. Hepatic arginase activity decreased significantly during the course of drug treatment. Progressive decrease in OTA, accompanied by hyperornithinemia, suggested decreased catabolism of ornithine. It is felt that these effects of clofibrate on enzyme systems unrelated to its lipid lowering action have far-reaching implications in hepatocarcinogenesis. PMID- 2893616 TI - Tenebrosin-A, a new cardiostimulant protein from the Australian sea anemone Actinia tenebrosa. AB - A new cardiac stimulatory protein, tenebrosin-A, has been isolated from the Australian sea anemone Actinia tenebrosa by gel filtration and cation-exchange chromatography, followed by cation-exchange HPLC. Its purity is established by analytical reversed-phase HPLC and N-terminal sequence analysis. According to SDS PAGE, its apparent Mr is 20,000 daltons. Amino acid analysis indicates that it contains 186 residues, and is devoid of cysteine or cystine. Tenebrosin-A exerts a strong positive inotropic effect on isolated guinea pig atria at a concentration of 1.4 nM, with little chronotropic activity. PMID- 2893617 TI - The heterogeneity of arylsulphatase-A and arylsulphatase-B in normal human urine and urine from cancer patients. AB - Arylsulphatase-A and arylsulphatase-B heterogeneity in normal and cancer patient urine was investigated using high resolution agarose isoelectricfocusing. Normal urine contained up to nine forms of arylsulphatase-A activity with isoelectric points from 4.45 to 5.43 and at least 5 forms of arylsulphatase-B between 8.58 and 9.15 along with a broad zone of activity between pH 6.5 and 7.6. Although cancer patients had significantly higher levels of arylsulphatase-A and arylsulphatase-B activity, their pattern of activity was essentially the same as for the normals with only minor quantitative differences in some peaks. PMID- 2893618 TI - Gas phase sequencing of the proteolipid subunit 9 of the human H+-ATPase in the presence of cetyltrimethylammonium bromide. AB - The compatibility of cetyltrimethylammonium bromide (CTAB), a quaternary ammonium compound with detergent properties, with gas phase protein sequencing has been examined. Two proteins, one hydrophilic (sperm whale apomyoglobin) and one hydrophobic (the proteolipid subunit 9 of the human mitochondrial H+-ATPase), were successfully sequenced in the presence of this detergent. The presence of CTAB did not affect the repetitive yield during sequencing when compared with polybrene although at high detergent concentrations the initial yield was apparently lower. The sequence of the first forty amino acid residues of the human H+-ATPase proteolipid subunit 9 shows complete homology to the bovine sequence. PMID- 2893619 TI - Prevention of alterations in the transport of nutrients in pyelonephritic rats by immunization with pili. AB - The uptake of D-glucose, L-aspartate, L-lysine and L-proline was studied in renal brush border membrane vesicles prepared from control, infected and actively immunized-infected rats. The uptake of D-glucose, L-lysine and L-proline was decreased significantly (p less than 0.05) during the course of infection in the infected animals. However, the uptake of L-aspartate was increased significantly (p less than 0.05) in early stages and decreased significantly (p less than 0.05) in later stages of infection in the infected animals. When the animals were actively immunized with pili, still there were changes in the uptake of D-glucose and L-aspartate, but the changes appeared later and less pronounced. No change in the uptake of L-lysine and L-proline was observed in the immunized-infected animals. The findings demonstrated that active immunization with pili prevents alterations in the uptake of nutrients in pyelonephritic rats. PMID- 2893620 TI - Angiotensin metabolism by cerebral microvascular aminopeptidase A. AB - Porcine cerebral microvessels were isolated by differential sieving and centrifugation and were characterized by microscopic examination and marker enzyme enrichment (gamma-glutamyltransferase; EC 2.3.2.2). Purified microvessels contained a membrane-bound enzyme immunologically indistinguishable from renal aminopeptidase A (AmA; EC 3.4.11.7). AmA hydrolyzed both alpha-glutamyl- and alpha-aspartyl-2-naphthylamide, and hydrolysis was competitively inhibited by angiotensin II. Micro-vessel AmA hydrolyzed the N-terminal Asp1-Arg2 bond of both angiotensin I and angiotensin II, whereas the angiotensin II antagonist saralasin [(Sar1, Ala8)angiotensin II] was resistant to N-terminal hydrolysis. Angiotensin metabolism was optimal at pH 8.5 and was inhibited by EDTA, o-phenanthroline and amastatin. Conversely, inhibitors of neutral endopeptidase (phosphoramidon), post proline cleaving enzyme (Z-Pro-Prolinal), carboxypeptidase N [D-L-mercaptomethyl 3-guanidinoethylthiopropanoic acid (MERGETPA)] and angiotensin I converting enzyme (captopril) had no effect. The Km values of angiotensin I, angiotensin II and (Asn1, Val5)angiotensin II for microvessel AmA were 40.1 +/- 8.2, 35.3 +/- 4.3 and 156 +/- 22 microM respectively. Cerebral microvascular aminopeptidase A may play a role in vivo in modulating angiotensin-mediated local cerebral blood flow, and in preventing circulating angiotensins from crossing the blood-brain barrier. PMID- 2893621 TI - Induction of microsomal epoxide hydrolase by nitrosamines in rat liver. Effect on messenger ribonucleic acids. AB - Nitrosomethylethylamine and nitrosomethylpropylamine were found to be more potent inducers of rat liver microsomal epoxide hydrolase (styrene oxide hydrolase) than nitrosodiethylamine or nitrosodimethylamine. The time course of induction following a single administration of nitrosodimethylethylamine, nitrosomethylpropylamine or nitrosodiethylamine each showed a delay of 24 hr during which enzyme activity was unaltered. After that time activity increased and reached a maximum at between 72 and 120 hr. Increased enzyme activity following NDEA was paralleled by changes in the content of epoxide hydrolase in microsomes as measured by Western blots. Nitrosamines caused an increase of mRNA for epoxide hydrolase which was detected by probing Northern blots with a [32]-P labelled epoxide hydrolase cDNA and by in vitro translation of polyadenylated mRNA. Both methods showed a maximal increase at 72 hr after nitrosodiethylamine treatment but a significant increase was also observed at 24 hr although at this time no increase in enzyme activity was apparent. PMID- 2893622 TI - Biochemical characterization of glutathione-deficient mutants of Escherichia coli K12 and Salmonella strains TA1535 and TA100. AB - Glutathione-deficient mutants of Escherichia coli K12/343/408 and Salmonella typhimurium TA1535 and TA100 were characterized biochemically by measuring the rate of formation of (14C)gamma-glutamylcysteine and (14C)glutathione in cell free extracts of the strains. gamma-Glutamylcysteine synthetase activity was found to be absent in the NGR-2 mutant of E. coli and in the Salmonella mutants TA1535/NG-19, TA100/NG-57 and TA100/NG-11, while only low activities were found in the NGR-9 and NG-54 mutant of E. coli and Salmonella respectively. These results correspond with the decreased levels of glutathione found in these strains. Extracts of the parent strains have normal glutathione levels and show high gamma-glutamylcysteine synthetase activities. It is concluded that the present GSH-deficient strains of E. coli and Salmonella are gshA mutants, analogous to those previously described in E. coli. In addition, the present results show that the fluorometric method used for the determination of glutathione, employing o-phthalaldehyde as a reagent, is not specific for glutathione (at pH 8.0), but also sensitively reacts with gamma-glutamylcysteine. PMID- 2893623 TI - Neuropharmacology of a new psychotropic 2,3-benzodiazepine. AB - 1-(3-Chlorophenyl)-4-methyl-7,8-dimethoxy-5H-2,3-benzodiazepine (GYKI 51189) is a new analogue of tofisopam. Due to the novel chemical structure this molecule displays a peculiar spectrum of pharmacological activity. In many respects tofisopam and its new analogue differ from the traditional 1,4-benzodiazepines, e.g. in that they possess selective anxiolytic action without muscle relaxant and anticonvulsive activity, as well as they do not show any affinity for the 1,4 benzodiazepine receptors. This new compound exerts more pronounced anxiolytic potency than tofisopam. In addition to its main action it possesses significant antidepressant activity. It attenuates psychomotor agitation and exerts significant antiaggressive effect by reducing both spontaneous and induced aggressiveness. Vegetative responses (rise in blood pressure and heart rate) induced by electric stimulation of the hypothalamus are also inhibited by this compound, while motor functions remain unaffected and no somnolence is induced. The new tofisopam analogue fails to exert any potentiating effect either on ethanol or on barbiturates. GYKI-51189 has a highly favourable therapeutic index and only few side effects. Neither tolerance nor dependence was observed during the chronic toxicological investigations. PMID- 2893624 TI - Pharmacokinetic and pharmacodynamic effects of the novel benzodiazepine antagonist 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one in humans. AB - 2-Phenylpyrazolo[4,3-c]quinolin-3(5H)-one (CGS 8216) is pharmacologically characterized as benzodiazepine antagonist with low inverse agonistic effects. Single oral doses up to 650 mg and subchronic doses up to 100 mg daily for seven days are well tolerated by young healthy volunteers. Plasma concentrations of CGS 8216 are variable, not dose-related and relatively low considering the doses administered. A high plasma concentration ratio of metabolite vs. parent compound (3:1) points to an extensive gastrointestinal first-pass metabolism. CGS 8216 influences the human electroencephalogram similar to anxiolytic and vigilance enhancing drugs in doses which do not change performance of psychometric tests. CGS 8216 antagonizes the diazepam-induced impairment of alertness. PMID- 2893625 TI - [Synthesis and pharmacologic action of substituted imidazolyl- and thiazolylmethylthioethylguanidine]. AB - Starting with diphenyl N-benzoyl-carbonimidate impromidine analogues characterized by various substituted imidazole or thiazole groups instead of the 5-methylimidazole part have been synthesized and tested for H2-agonistic and H1 antagonistic activity as well. The most potent substances 6h,i are 20-30 times more active than histamine at the H2-receptors in the isolated spontaneously beating guinea-pig right atrium. In isolated perfused guinea-pig hearts 6h,i were found to predominantly stimulate heart rate, whereas the increase in LVdp/dtmax was about 40% of impromidine's maximal response. PMID- 2893627 TI - Urinary metabolism of chlorphenoxamine in man. AB - After an oral dose of 40 mg of 4-chlorophenyl-methylbenzyloxy-N,N-dimethyl ethylamine(chlorphe noxamine, Systral) urinary metabolism was studied by gas chromatography/mass spectrometry. Besides the unchanged drug, 8 metabolites and 7 artifacts and derivates could be identified. Metabolism is similar to that of the structurally related antihistaminic drugs diphenhydramine and doxylamine. The main metabolic pathways are: 1. N-demethylation, 2. oxidative desamination and formation of an alcohol and a carbonic acid derivative, 3. cleavage of the ether bond, and 4. hydroxylation of the phenyl ring. For determination of chlorphenoxamine in plasma an assay using gas chromatography was developed. Chlorphenoxamine plasma levels were beyond the limit of detection (10 ng/ml) 30, 60, 120, 240, 480, and 1200 min after oral intake. PMID- 2893626 TI - [Synthesis and pharmacologic action of arylmethylethylguanidines]. AB - Impromidine analogous guanidines have been prepared characterized by H2 unspecific arylmethyl groups instead of the 5-methylimidazole residue. The most potent substances proved to be about 20 times more active than histamine at the isolated spontaneously beating guinea-pig right atrium (H2-agonism), simultaneously showing moderate H1-antagonistic activity at the guinea-pig ileum. In isolated perfused guinea-pig hearts the thenylthioethylguanidine 9e was very potent in increasing LVdp/dtmax, achieving about 90% of impromidine's maximal response. In comparison with impromidine the increase in heart rate was lower and rhythm disturbances were substantially reduced. PMID- 2893628 TI - [Malignant mixed mesodermal tumor with endocrine cells of the corpus uteri]. AB - A case of uterine malignant mixed mesodermal tumor harboring endocrine cells is reported. Endocrine cells were immunocharacterized as serotonin, somatostatin and pancreatic polypeptide cells. This variety of mixed mullerian tumor is added to other endocrine cells-containing neoplasms of the uterus. PMID- 2893629 TI - On cholinergic mechanisms in the optokinetic nystagmus of the frog: antagonistic effects of muscarinic and nicotinic systems. AB - In a monocular situation, an intravitreal injection of acetylcholine (ACh) agonists (especially muscarinic agonists like muscarine or oxotremorine) provoked both the suppression of the optokinetic nystagmus (OKN) related to the injected eye, and the appearance of a nasal-temporal (N-T) component in the OKN triggered by the contralateral non-injected eye. These two effects were added in a binocular condition. Similar results were obtained with ACh nicotinic antagonists (D-tubocurarine, alpha-bungarotoxin, hexamethonium and gallamine). ACh muscarinic antagonists (atropine, scopolamine) had only moderate effects and failed to provoke an N-T component in the contralateral OKN. These data show that ACh mechanisms are involved in the control of the frog OKN, especially in directional asymmetry, nicotinic and muscarinic systems acting in an antagonistic way. PMID- 2893630 TI - CNS monoamine levels and the effect of DSP4 on ethanol sensitivity in LS and SS mice. AB - Brain area monoamine levels were determined in selectively-bred ethanol sensitive (LS) and insensitive (SS) mice. Norepinephrine, dopamine and serotonin were measured using high performance liquid chromatography coupled with electrochemical detection. Brain regions studied included cerebellum, brain stem, striatum, frontal cortex, hippocampus and hypothalamus. LS and SS mice exhibited similar regional monamine levels with the exception of differences in brain stem and cerebellar norepinephrine levels. The role of norepinephrine in regulating ethanol sensitivity of these mice was investigated using the neurotoxin, DSP4 (selectively lesions central noradrenergic pathways). Treatment with DSP4 did not alter ethanol sensitivity in the LS or SS mice, measured by duration of righting response loss and blood ethanol concentration at its recovery. Differences in brain stem and cerebellar norepinephrine levels between the LS and SS mice were considerably smaller than the large decreases in levels produced in both lines by DSP4. It is concluded that although synaptically-released monoamines may influence ethanol responses, norepinephrine probably does not directly mediate differences in behavioral sensitivity to ethanol between these mouse lines. PMID- 2893631 TI - A spectrophotometric method for the determination of gamma-glutamyl cyclotransferase with alanine dehydrogenase in the presence of anthglutin. AB - gamma-Glutamyl cyclotransferase activity is assayed in tissues by a colorimetric method using gamma-glutamyl alanine as a substrate coupled with alanine dehydrogenase from B. sphericus, to measure the formation of NADH. In order to avoid interference by the reaction catalyzed by gamma-glutamyl transpeptidase, anthglutin, a specific inhibitor of the transpeptidase was included in the reaction mixture. The Km value of rat kidney gamma-glutamyl cyclotransferase with respect to gamma-glutamyl alanine appeared to be the same when determined by either the colorimetric or the radiometric method. This assay presents a reliable alternative to the use of radiolabeled substrate and is used for the assay of gamma-glutamyl cyclotransferase in a variety of physiological and experimental samples. PMID- 2893632 TI - Absence of antibodies to HIV-2/HTLV-4 in six central African nations. AB - We studied 1508 individuals from Zaire, Burundi, Tanzania, Zambia, Kenya, and Cameroon for antibodies to HIV-2/HTLV-4. AIDS, ARC, other disease or tumor patients and healthy people were sampled from 1984-1986. By radioimmunoprecipitation and SDS/PAGE analysis and/or Western blot we failed to find any samples with specific antibodies to HIV-2/HTLV-4 indicative of infection. In contrast, 363 of these 1508 individuals demonstrated antibodies to HIV-1/HTLV-3B by the same serologic assays. HIV-2/HTLV-4 infection appears to be quite rare in Central Africa. AIDS and related syndromes in this study were exclusively correlated with HIV-1 infection. Studies in West Africa have shown high rates of infection with HIV-2/HTLV-4 where cases of AIDS are still relatively uncommon. These results indicate that HIV-2/HTLV-4 has a distinct geographic distribution from that of HIV-1 in Africa. Further studies are necessary to better define the pathogenicity and natural history of this distinct new virus, HIV-2/HTLV-4. PMID- 2893633 TI - [The influences of neurotransmitters on the traumatic unconsciousness, immediate convulsion and mortality in the experimental mice model]. AB - In order to clearing the influence of neurotransmitters in concussive unconsciousness, immediate convulsion and mortality, the following experiments were performed. Awake male mice of dd-strain were restrained and subjected to head injury using a bakelite weight of 30 gm dropped from a height of 20 cm on to the skull. This injury resulted in immediate loss of consciousness in 100%, convulsive seizure in 66% and death in 30% of animals. The severity of consciousness disturbance was evaluated by two parameters; (1) time interval required for the recovery of righting reflex (RR) and (2) time interval for the recovery of spontaneous movement (SM). Agonist or antagonist of various neurotransmitters was given intraperitoneally 0.5 or 2 hours before injury. The following results were obtained although some of them were statistically not significant. Physostigmine shortened both RR (p less than 0.1) and SM (p less than 0.01), whereas scopolamine did not change these intervals. Atropine sulfate shortened both of them. Nevertheless, atropine methylbromide, which dose not pass through blood-brain-barrier, also had same effects. Methamphetamine shortened both RR (p less than 0.1) and SM (p less than 0.05), whereas haloperidol prolonged these intervals. 5-HTP shortened RR (p less than 0.05), but prolonged SM (p less than 0.1). Methysergide shortened both RR (p less than 0.05) and SM (p less than 0.01). Convulsive seizure was suppressed by physostigmine (p less than 0.01) or 5-HTP (p less than 0.20). These results suggested that suppression of dopaminergic and cholinergic systems, and/or activation of serotonergic system contribute to concussive unconsciousness. PMID- 2893634 TI - An assessment of the partial agonist activity of Ro 31-1118, flusoxolol and pindolol in man. AB - 1. The effects of single oral doses of three beta-adrenoceptor partial agonists (Ro 31-1118, flusoxolol and pindolol), two beta-adrenoceptor antagonists (propranolol and atenolol), two beta-adrenoceptor agonists (salbutamol and prenalterol) and placebo on sleeping heart rate, quality of sleep, supine heart rate, exercise heart rate, blood pressure, forearm blood flow and finger tremor were studied in eight healthy male volunteers. 2. Sleeping heart rate was increased by Ro 31-1118, flusoxolol, pindolol, salbutamol and prenalterol and decreased by propranolol and atenolol. 3. None of the drugs studied affected quality of sleep. 4. Supine heart rate was increased by flusoxolol, prenalterol and salbutamol, unaffected by Ro 31-1118 and pindolol and reduced by propranolol and atenolol. 5. Exercise heart rate was reduced by both beta-adrenoceptor antagonists and the three partial agonists and unaffected by salbutamol and prenalterol. 6. Systolic blood pressure was increased by Ro 31-1118, flusoxolol, salbutamol and prenalterol, unaffected by pindolol and reduced by propranolol and atenolol. Diastolic blood pressure was reduced by salbutamol and prenalterol. 7. Forearm blood flow was increased by Ro 31-1118, salbutamol and prenalterol, unchanged by pindolol and flusoxolol and decreased by atenolol and propranolol. 8. Finger tremor was increased by Ro 31-1118, flusoxolol, pindolol, salbutamol, and prenalterol. 9. beta-adrenoceptor partial agonists have different effects on the cardiovascular system and finger tremor to beta-adrenoceptor antagonists. 10. While Ro 31-1118 and flusoxolol are antagonists mainly at the beta 1-adrenoceptor they have agonist activity at both beta 1- and beta 2 adrenoceptors. 11. While pindolol is a non-selective antagonist its agonist activity is mainly at the beta 2-adrenoceptor. PMID- 2893635 TI - The assessment of the beta-adrenoceptor blocking activity and cardioselectivity of Koe 3290 in normal subjects. AB - 1. The beta-adrenoceptor antagonist activity, cardioselectivity and antilipolytic properties of Koe 3290 were investigated in healthy subjects. 2. Koe 3290 12.5, 25, 50 and 100 mg, atenolol 25, 50 and 100 mg and placebo were given in double blind randomised order to eight subjects. All doses of both Koe 3290 and atenolol reduced supine, standing and exercise heart rate (P less than 0.02). From 2 to 8 h after administration the exercise heart rate after Koe 3290 100 mg was similar to that for atenolol 50 mg. 3. The cardioselectivity of Koe 3290 and atenolol was compared. Koe 3290 50, 100 and 150 mg, atenolol 50 and 100 mg and placebo were given to six subjects in a double-blind random order. Isoprenaline dose-response curves were constructed for cardiovascular parameters and finger tremor. 4. For doses which were equipotent at the beta 1-adrenoceptor (Koe 3290 100 mg and atenolol 50 mg) atenolol caused less attenuation of heart rate, diastolic blood pressure, forearm blood flow and finger tremor (P less than 0.02). 5. There was no difference in the isoprenaline-induced changes in serum free fatty acids, blood glucose, plasma lactate or potassium after Koe 3290 and atenolol. Koe 3290 attenuated the rise in serum insulin more than atenolol (P less than 0.02). 6. Koe 3290 is an effective beta-adrenoceptor blocking drug in man. It is not as cardioselective as atenolol and does not possess specific antilipolytic properties. PMID- 2893636 TI - Comparison of ketanserin and slow-release nifedipine added to the treatment of hypertensive patients uncontrolled by a thiazide diuretic plus beta-adrenoceptor blocker. AB - 1. Ketanserin or slow-release nifedipine were added to the treatment of 24 patients with hypertension uncontrolled by a thiazide diuretic plus beta adrenoceptor antagonist in an observer-blind, randomised parallel-group study of 6 months duration. 2. At 6 months the mean falls in supine blood pressure were for ketanserin (mean daily dose 77 mg) 7/5 mm Hg and for nifedipine (mean daily dose 62 mg) 27/10 mm Hg. The difference between the treatments was significant for systolic blood pressure (P less than 0.02) and mean arterial pressure (P less than 0.05). Six nifedipine-treated patients reached target blood pressure, compared with one patient with ketanserin (P less than 0.02). 3. One patient taking nifedipine, and none taking ketanserin withdrew because of side-effects. The tolerability of the two drugs was broadly similar. 4. Ketanserin treatment was associated with significant changes in supine pulse rate (-8 beats min-1, P less than 0.05) and corrected QT interval (+27 ms, P less than 0.05). Nifedipine treatment had no effect on these variables. The change in pulse rate was significantly different between the groups. 5. In patients treated with a diuretic and beta-adrenoceptor blocker who required additional treatment ketanserin was significantly inferior to nifedipine. PMID- 2893637 TI - Comparative effect of famotidine and cimetidine on the pharmacokinetics of theophylline in normal volunteers. AB - The comparative effect of famotidine or cimetidine on theophylline disposition was determined in healthy volunteers. Cimetidine, but not famotidine, caused a reduction in the rate of elimination of theophylline. The mean total body clearance of theophylline was reduced from 57.6 ml min-1 before cimetidine to 39.5 ml min-1 during cimetidine; and the half-life was prolonged from 8.7 h before cimetidine to 12 h during cimetidine. The volume of distribution and renal excretion of theophylline were not affected by either famotidine or cimetidine. PMID- 2893638 TI - Temelastine does not affect theophylline pharmacokinetics in normal subjects. AB - The pharmacokinetics of theophylline (i.v. aminophylline 250 mg) were studied in a balanced, double-blind crossover following the administration of oral temelastine (100 mg) or placebo, twice daily for 7 days, to 10 normal volunteers. Comparison of volumes of distribution, elimination rate constants, elimination half-lives and areas under the plasma concentration-time curve indicated that temelastine had no significant effect on theophylline pharmacokinetics. PMID- 2893641 TI - Membrane contents of distinct subpopulations of coated vesicles determined by scanning transmission electron microscopy. AB - In order to investigate the heterogeneity of clathrin-coated vesicles purified from rat liver, and to quantitate rigorously their membrane contents, we have analyzed scanning transmission electron micrographs of unstained coated vesicles before and after extraction with the non-ionic detergent Triton X-100, as well as of vesicles whose coats had been removed by dialysis against 10 mM or 100 mM Tris (pH 8.2). Their respective distributions of particle masses were thus determined and compared, in light of complementary biochemical quantitations of lipid and protein. Smaller coated particles, 25-45 MDa in mass and 60-80 nm in diameter, lose no mass when extracted with Triton, and disappear when their coats are dissociated. We conclude that they do not contain membrane vesicles, although they have dense, presumably proteinaceous, cores. They may represent particles generated during tissue homogenization or, possibly, a storage form of clathrin. The remaining 70% contain bona fide vesicles: these particles are 75-150 nm in diameter, and their average mass is about 80 MDa, of which 48 MDa is contributed by coat proteins, 10-12 MDa by phospholipid and cholesterol, and 20-22 MDa by vesicle-associated proteins. Their vesicles are of two types: smaller, denser, vesicles that contain substantial amounts of internalized material, and larger, less dense, vesicles that do not. The distinction between them may, in view of other findings, reflect a difference between coated vesicles derived respectively from the Golgi and the plasma membrane. PMID- 2893639 TI - Choline deficient diet enhances the initiating and promoting effects of methapyrilene hydrochloride in rat liver as assayed by the induction of gamma glutamyltranspeptidase-positive hepatocyte foci. AB - Earlier we demonstrated that short-term feeding of methapyrilene hydrochloride (MPH) and of a choline deficient (CD) diet to rats induced peroxidative damage of microsomal membrane lipids of liver cells. In the present study, we investigated whether a CD diet modifies the extent of MPH-induced lipid peroxidation and whether the modifications lead to changes in the initiating and promoting action of these agents using assays of the induction of gamma-glutamyltranspeptidase (GGT)-positive hepatocyte foci. Addition of 0.1% MPH to a CD diet enhanced the extent of microsomal lipid peroxidation induced by a CD diet alone. Feeding a choline supplemented (CS) or a CD diet containing 0.1% MPH for 2 weeks followed by 7 weeks promotion by a CD diet plus phenobarbital was ineffective in inducing GGT-positive foci. Feeding MPH in a CS or a CD diet for 4 weeks, however, resulted in the development of substantial numbers of GGT-positive foci. There was a 3 fold increase in the number of foci in rats initiated with a CD + MPH diet over that in rats initiated with a CS + MPH diet. 0.1% MPH in a CS diet or a CD diet exerted significant promotional effects on the induction of GGT-positive foci in rats initiated with a single injection of diethylnitrosamine. Addition of MPH to a CD diet was additive in inducing GGT-positive foci. The results suggest that lipid peroxidation of the liver may be involved in the carcinogenic and/or promoting effects of MPH and a CD diet. PMID- 2893640 TI - Use of a somatostatin analogue in association with surgery and hepatic arterial embolisation in the treatment of the carcinoid syndrome. PMID- 2893642 TI - Altered plasma membrane ultrastructure in multidrug-resistant cells. AB - Multidrug resistance is mediated by P-glycoprotein, an integral plasma membrane component which is thought to function as a drug export pump. This model can explain drug resistance, but fails to account for the broader pleiotropy of the multidrug resistance phenotype. We report here a freeze-fracture study revealing increases in the densities of protoplasmic face intramembrane particles in multidrug-resistant Chinese hamster ovary (CHO) and human leukemic cells. The intramembrane particle density in a CHO cell revertant which had lost the characteristics of the multidrug resistance phenotype was indistinguishable from that of the drug-sensitive parental cell line. This demonstration of a global multidrug resistance-linked change in plasma membrane architecture may have significant implications for understanding the variety of concurrent membrane related changes which are not easily explained by the current model for multidrug resistance. PMID- 2893643 TI - Choline-phosphate cytidyltransferase activity and phosphatidylcholine synthesis in rat granular pneumocytes are increased with exogenous fatty acids. AB - We investigated the effect of exogenous fatty acids on phosphatidylcholine (PC) and disaturated phosphatidylcholine (DSPC) synthesis by rat granular pneumocytes in primary culture. Synthesis of PC and DSPC from [3H-methyl]choline, as evaluated by increasing specific activity (pmol choline incorporated/microgram phosphorus), was linear for 3 h. Exogenous palmitic, oleic, linoleic, or linolenic acid (100 microM each) increased the synthesis of PC by approx. 50% during incubation for 3 h. In contrast, synthesis of DSPC was increased only by palmitic acid. The increase in DSPC synthesis was approx. 150% after 3 h. Conversion of choline phosphate to PC was increased in the presence of palmitic or oleic acid as indicated by pulse-chase studies with [3H-methyl]choline in the intact cells. Cells incubated for 3 h with either oleic or palmitic acid showed increased choline-phosphate cytidyltransferase activity in the cells and the microsomal fraction. In addition, oleic acid increased the activity of this enzyme in the cytosolic fraction. The distribution of this enzyme in cytosolic and microsomal fraction was 24 and 76% in the cells incubated with palmitic acid and 32 and 68% in control cells. These results suggest that exogenous fatty acids stimulate the de novo pathway of PC synthesis in granular pneumocytes by increasing the microsomal choline-phosphate cytidyltransferase activity. PMID- 2893644 TI - Transglutaminase-catalysed cross-linking of proteins phosphorylated in the intact glucose-stimulated pancreatic beta-cell. AB - Incubation of intact islets in the presence of [32P]Pi and stimulatory levels of glucose followed by separation of phosphorylated islet proteins by SDS polyacrylamide gel electrophoresis revealed the presence of a high molecular weight phosphopolymer which did not transverse a 3% (w/v) acrylamide gel. The majority of this phosphopolymer (approx. 70%) was present in the 600 x g sedimented fraction of islet homogenates. Islet homogenates obtained from intact islets previously incubated with [32P]Pi and stimulatory levels of glucose when incubated under conditions that activated the islet transglutaminase resulted in an increase in the amount of phosphopolymer present in the 600 x g sedimented fraction. Inhibitors of transglutaminase activity which are known to inhibit glucose-stimulated insulin release led to a significant reduction in the fraction of phosphopolymer present in the glucose-stimulated intact islet. These findings suggest that protein cross-linking and phosphorylation reactions may be closely linked in the pancreatic beta-cell. PMID- 2893645 TI - Opioids: mediators of fear or mania. PMID- 2893646 TI - Tardive dysmentia in Hungary. PMID- 2893648 TI - The development of new drugs for the treatment of schizophrenia. AB - Currently available anti-psychotic drugs owe much of their efficacy in schizophrenia to their ability to block dopamine receptors in specific areas of the brain. This article reviews the mechanisms action and side effects of drugs used for schizophrenia, and describes approaches to the development of new treatments. PMID- 2893647 TI - The right to refuse treatment under Rogers v. Commissioner: preliminary empirical findings and comparisons. AB - Preliminary findings on the effects of the Massachusetts ruling in Rogers v. Commissioner, an important right to refuse treatment case, are compared with models in other jurisdictions. In sum, few cases are reviewed; in almost all reviewed, the court overrides the patients' refusal. The case raises troubling implications about due process and quality of care. PMID- 2893649 TI - Dental and facial injuries in international field hockey. AB - In many respects international sportsmen are trendsetters for the behaviour of recreational sportsmen. For this reason the attitude of international hockey players towards mouth protectors was studied. The possession and use of mouth protectors vary markedly between different countries. The incidence of dental facial traumas among international field hockey players is high; 54% had sustained injuries necessitating a visit to a physician and/or a dentist. Of these victims 20% sustained serious dental damage at least once (women 16% and men 22%). Only 20% of the international players wear a mouth protector consistently during training and matches. Women use the apparatus almost twice as much as men. The main argument in rejecting a mouth protector is that it is not felt to be necessary. PMID- 2893650 TI - Development of long term use of psychotropic drugs by general practice patients. AB - From 1984 to 1986 a prospective study was conducted of 104 general practice patients who started treatment with a benzodiazepine or an antidepressant drug. The duration of reported use of the drugs was two months for 45% of patients, four months for 17% of patients, and six months for 15%. Type of drug, age, and level of education were found to be predictive of continuing use. General practitioners have a significant effect on their patients' use of drugs and, with careful selection and review when prescribing, may help to prevent dependence on psychotropic drugs. PMID- 2893651 TI - Further evidence of noradrenergic regulation of rat hypothalamic estrogen receptor concentration: possible non-functional increase and functional decrease. AB - The regulation of estrogen receptors by the alpha 2-noradrenergic system was studied. A single injection of the alpha 2-noradrenergic antagonist, yohimbine, caused a biphasic effect on the concentration of cytosol estrogen receptors in the mediobasal hypothalamus and anterior pituitary gland. A short-latency increase was seen at 1.5-3 h, followed by a longer-lasting decrease at 8-16 h. Scatchard analysis revealed that the apparent, short-latency increase is in the concentration of binding sites, not in the affinity of the receptor for [3H]estradiol. The increase in the concentration of cytosol estrogen receptors is not blocked by pretreatment with the alpha 2-noradrenergic agonist, clonidine. In addition, no increase is detected in the concentration of cell nuclear estrogen receptors accumulating in response to a saturating dose of estradiol. Therefore, the apparent increase in the concentration of cytosol estrogen receptors may not represent a functional increase in receptors. The decrease in the concentration of estrogen receptors, which occurs 8-16 h after yohimbine treatment, is also seen after injection of the alpha 2-adrenergic antagonist, idazoxan, and is not due to a change in the in vitro rate of association of the receptors with [3H]estradiol. Furthermore, the decrease seems to be a functional decrease in the concentration of receptors capable of cell nuclear accumulation in response to estradiol injection, as indicated by the results of experiments in which the concentration of cell nuclear estrogen receptors was assayed after estradiol injection. These experiments provide further support for the hypothesis that the alpha-noradrenergic system, and perhaps specifically the alpha 2-subtype, is involved in decreasing the concentration of estrogen receptors in parts of the brain and pituitary gland. This interaction provides a mechanism by which the environment could regulate the sensitivity of certain neurons to estradiol. However, the finding that the initial increase in the concentration of cytosol estrogen receptors after yohimbine treatment is not followed by the predicted increase in cell nuclear estrogen receptors after estradiol injection raises questions about the physiological relevance of the apparent increase under some conditions. PMID- 2893652 TI - Effect of the 5-HT1A receptor agonist ipsapirone on the local cerebral glucose utilization of the rat hippocampus. AB - Local cerebral glucose utilization (LCGU) was measured in the hippocampus of the rat brain following i.p. injection of the anxiolytic drug and 5-HT1A receptor agonist ipsapirone (TVX Q 7821). Administration of ipsapirone (5 mg/kg) reduced glucose utilization in the various hippocampal areas to variable extent. The most subtle reduction took place in the dorsal subiculum, while the most pronounced decrease was found in sector CA4 of Ammon's horn. The degree of LCGU reduction can be related to the 5-HT1A receptor density in the respective areas. PMID- 2893653 TI - Intrathecal dynorphin A1-13 and dynorphin A3-13 reduce rat spinal cord blood flow by non-opioid mechanisms. AB - Radiolabeled microspheres were used to examine the effects of paralytic intrathecal doses of dynorphin A (Dyn A1-13) and Dyn A3-13 on rat brain and spinal cord blood flows and cardiac output. Dyn A1-13 produced significant dose related reductions in blood flow to lumbosacral and thoracic spinal cord without altering cardiac output and blood flow to brain and cervical spinal cord. Naloxone failed to block these effects. Dyn A3-13, which lacks opioid activity, also significantly reduced blood flow in lumbosacral spinal cord. Thus, the paralytic effects of Dyn A in the rat may involve reductions in spinal cord resulting from non-opioid actions of Dyn A. PMID- 2893655 TI - Corticotropin-releasing hormone (CRH) is decreased in the basal ganglia in Huntington's disease. AB - Corticotropin-releasing hormone-like immunoreactivity (CRH-IR) was measured in control and Huntington's disease brain tissues obtained postmortem. The concentration of CRH-IR was markedly decreased in the caudate/putamen in Huntington's disease; the concentration of somatostatin-like immunoreactivity measured in the same extracts was significantly increased in the caudate/putamen in Huntington's disease compared with the control group. In contrast to previously reported decreases in CRH-IR in the cerebral cortex in Alzheimer's disease, Parkinson's disease and progressive supranuclear palsy, no significant differences were observed in the concentrations of CRH-IR between controls and Huntington's disease in frontal, parietal, temporal, occipital and cingulate cortex and in globus pallidus. PMID- 2893654 TI - Effects of drugs which modify catecholamine activity on amplification of LH release induced by locus coeruleus electrical stimulation. AB - Norepinephrine may be the neurotransmitter responsible for triggering the surge release of luteinizing hormone (LH) in proestrous and steroid-treated ovariectomized rats. In a previous study, we electrically stimulated (ES) the locus coeruleus (LC), a norepinephrine cell body region from which some axons project to the hypothalamus. These studies were performed in estradiol-treated rats in which the medial preoptic nucleus (MPN) initially had been electrochemically stimulated (ECS) to partially depolarize luteinizing hormone releasing hormone (LH-RH) neurons. We observed that LC-ES markedly amplified the amount of LH released after preoptic-ECS. The purpose of the present study was to determine if these amplifying effects of LC-ES were due to the release of a catecholamine and if so which neurotransmitter was involved in this response. All rats in this study were ovariectomized and 7 days later (day 0) they were treated with estradiol for 2 days (day 2). On day 2, all animals were anesthetized with chloral hydrate. In control rats, the MPN was electrochemically stimulated (100 microA/60 s DC) and 30 min later the LC was electrically stimulated for 15 min. MPN-ECS significantly increased plasma concentrations of LH and LC-ES markedly amplified these plasma LH levels. Thereafter, 3 studies were performed and the following drugs were given: (1) alpha-methyl-p-tyrosine (MPT, 300 mg/kg i.p.); (2) phenoxybenzamine (PX, 15 mg/kg i.p.) and (3) propranolol (PROP, 15 mg/kg i.p.). MPT and PROP were administered 15 min prior to MPN-ECS and PX was given 90 min before MPN-ECS. None of these drugs affected the amount of LH released after preoptic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893656 TI - Chlorpromazine, but not chlorpromazine sulphoxide, stimulates transmitter release from motor nerve terminals. AB - Treatment of frog neuromuscular preparations with chlorpromazine (5 mumol/l) resulted in a marked rise in miniature endplate potential (MEPP) frequency of greater than 100% within 30 min, and an increase in evoked transmitter release (quantal content 5-15) of about 35%. Treatment with chlorpromazine sulphoxide (5 microM), a derivative of chlorpromazine with a much lower affinity for calmodulin, had very little effect on either form of transmitter release. It is concluded that stimulatory effects of calmodulin-binding drugs at the nerve terminal may well be exerted through calmodulin inhibition. The stimulatory effect of chlorpromazine on MEPP frequency was markedly reduced in preparations bathed in EGTA-containing Ca2+-free saline, but the response was largely restored by raising the temperature by 3-4 degrees C. It is argued that despite this partial dependence on [Ca2+]o, stimulation of transmitter secretion by chlorpromazine is likely to be mediated by inhibition of calmodulin-activated Ca2+-ATPases, and consequent elevation of [Ca2+]i. PMID- 2893657 TI - Biochemical and morphological effects of castration on the postorganizational development of the hypogastric ganglion. AB - The biochemical and morphological development of the sympathetic hypogastric ganglion (HG) was examined subsequent to postnatal castration at 10-11 days of age. Previous studies suggested that tyrosine hydroxylase (T-OH) activity, an index of noradrenergic maturation, and choline acetyltransferase (ChAT) activity, a marker for preganglionic terminal formation, were dependent on gonadal hormones during normal ontogeny. In the present studies, morphometric analyses of the HG revealed that the cross-sectional area of the cell soma and nucleus were significantly reduced following postnatal castration at day 10. Conversely, castration produced no change in the number of HG neurons. In addition, postnatal castration prevents the development of postsynaptic T-OH activity to a greater extent than ganglionic protein resulting in a significant loss of T-OH specific activity. In contrast, presynaptic ChAT activity was reduced in parallel with ganglionic protein, thus ChAT specific activity was unchanged. Testosterone replacement therapy, even in groups where treatment was delayed for up to 2 weeks after castration, completely reversed deficits in both T-OH and ChAT activities. These studies suggest that altered development of ganglion protein subsequent to postnatal castration is related to decreases in the size of neurons and not to the loss of neurons. The lack of cell loss also suggest that decreased levels of postsynaptic T-OH activity results from a loss of enzyme activity per cell and the decreased levels of ChAT activity probably represent fewer presynaptic terminals per neuron. In addition, delayed testosterone replacement subsequent to castration was effective in restoring enzyme activities suggesting an 'activational' not 'organizational' role for testosterone after postnatal day 10. PMID- 2893658 TI - Potential sites of interaction between catecholamines and LHRH in the sheep brain. AB - A combined immunoperoxidase/immunofluorescence procedure was used to examine potential sites of overlap between catecholamine and LHRH systems in the brains of ewes sacrificed during either anestrous or the breeding season. Cells and fibers immunoreactive for either tyrosine hydroxylase (TH) or dopamine-beta hydroxylase (DBH) were visualized in the same sections as immunopositive LHRH perikarya and fibers. TH- and DBH-positive varicosities in the preoptic area and anterior hypothalamus appeared to contact both LHRH cell bodies and their dendrites. Clusters of TH-positive cells and fibers were found in the organum vasculosum of the lamina terminalis, and partially overlapped the location of immunoreactive LHRH fibers in that structure. Immunoreactive TH and LHRH fibers were densely interspersed within the zona externa of the median eminence, particularly within its lateral portion. No obvious qualitative differences were apparent in either the distribution of catecholamine cells and fibers or their overlap with LHRH elements between the brains of anestrous and breeding season ewes. These observations suggest the possibility of catecholaminergic synaptic inputs onto LHRH neurons in the ewe, as well as the potential for interaction between catecholamines and LHRH at the level of the median eminence. PMID- 2893659 TI - Somatostatin antiserum blocks carbachol-induced increase of paradoxical sleep in the rat. AB - Injection of carbachol into the nucleus tractus solitarius (NTS) produced an increase of paradoxical sleep (PS). When somatostatin antiserum (SRIF-AS) was infused continuously following carbachol injection, the increase in PS was blocked. These results suggest that carbachol-induced increase in PS is mediated by somatostatin. In addition, they confirm the role of somatostatin in the generation of PS. PMID- 2893660 TI - Blood pressure effects of monoamine oxidase inhibitors--the highs and lows. AB - Clinical guidelines for the management of the most common side effects associated with monoamine oxidase inhibitors (postural hypotension and hypertensive episodes) are offered. When non-pharmacological interventions fail to alleviate MAOI induced postural hypotension, the use of volume expanders (salt tablets or fludrocortisone) may be effective alternatives to drug discontinuation. Phentolamine and chlorpromazine are traditional drug treatments for MAOI hypertensive emergencies. The newer drug treatments evolved in the last decade for treating hypertensive emergencies is not reflected in the psychiatric or emergency medicine literature on treating MAOI induced hypertensive states. Nifedipine, diazoxide, or sodium nitroprusside appear to be more rational choices for this problem. PMID- 2893661 TI - Multiple endocrine neoplasia type I with Cushing's disease, primary hyperparathyroidism, and insulin-glucagonoma. AB - A case of multiple endocrine neoplasia type I (MEN I) consisting of Cushing's disease, primary hyperparathyroidism, and insulin-glucagonoma is described. This condition was treated successfully by transsphenoidal pituitary adenomectomy, subtotal parathyroidectomy, and enucleation of pancreatic tumors. Histologic features showed a basophilic adenoma in the pituitary, chief cell hyperplasia in the parathyroid, and islet cell adenomas in the pancreas. The rarity of multiple endocrine hyperfunctioning states and the pathophysiology created by the combination of these three diseases in this patient are of interest. PMID- 2893662 TI - Chromosome instability in preleukemic states of adult T-cell leukemia (pre-ATL). AB - Chromosome analysis was performed on nine patients with subclinical adult T-cell leukemia (pre-ATL), who were asymptomatic ATL virus carriers. Fewer than 30% of their peripheral blood leukocytes were abnormal T-lymphocytes with nuclear abnormalities. ATL-associated antigen (ATLA) and anti-ATLA antibody were found in all patients. Eight had variable abnormal karyotypes in a fraction (5.0%-25.4%) of peripheral blood leukocytes stimulated with phytohemagglutinin or T-cell growth factor. There were no metaphases when a mitogen was not added. Four patients had a clonal chromosome abnormality. The chromosome abnormality seen in one patient was observed in the first study but not in a second study, when a different abnormality was seen. In five patients, an abnormal chromosome #14 with a break at band 14q11 was found. These findings indicate that unstable, chromosomally abnormal clones are characteristic of pre-ATL. PMID- 2893663 TI - Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. AB - Fifty-one primary human breast tumors were analyzed for amplification of the c erbB-2 protooncogene. Thirteen (25%) of the DNA samples contained multiple gene copies. Paraffin-embedded tumor sections, available from 47 of the cases, were stained with a c-erbB-2 specific antiserum. Eighty-three % (10 of 12) of the tumors containing amplified c-erbB-2 gene copies stained positively with the c erbB-2 specific antiserum (P = 0.03). Thirteen tumors containing single copy c erbB-2 sequences also stained positively with the antiserum. This suggests that mechanisms other than gene amplification may lead to elevated levels of c-erbB-2 protein. Finally, there was a statistically significant correlation between c erbB-2 protein expression and parameters used in breast cancer prognosis. Positive staining was associated with positive nodal status of the patient (P = 0.02) and with tumors showing a poor nuclear grade (P = 0.02). This is the first study showing that a determination of the level of c-erbB-2 protein in paraffin embedded tumor sections may have prognostic value for the course of human breast cancer. PMID- 2893665 TI - Degradation of bromazepam by the intestinal microflora. PMID- 2893664 TI - Impaired neurotransmitter uptake in PC12 cells overexpressing human Cu/Zn superoxide dismutase--implication for gene dosage effects in Down syndrome. AB - Rat PC12 cells expressing elevated levels of transfected human Cu/Zn-superoxide dismutase (CuZn-SOD) gene were generated. These transformants (designated PC12 hSOD) closely resembled the parental cells in their morphology, growth rate, and response to nerve growth factor, but showed impaired neurotransmitter uptake. The lesion was localized to the chromaffin granule transport mechanism. We found that the pH gradient (delta pH) across the membrane, which is the main driving force for amine transport, was diminished in PC12-hSOD granules. These results show that elevation of CuZnSOD activity interferes with the transport of biogenic amines into chromaffin granules. Since neurotransmitter uptake plays an important role in many processes of the central nervous system, CuZnSOD gene-dosage may contribute to the neurobiological abnormalities of Down's syndrome. PMID- 2893666 TI - Synthesis and activity of optical isomers of nipradilol. PMID- 2893667 TI - Kinetics and mechanism of the acid-base equilibrium of mexazolam and comparison with those of other commercial benzodiazepinooxazole drugs. PMID- 2893668 TI - [Traditional Chinese medicine typing of schizophrenia]. PMID- 2893669 TI - Intracoronary alpha 2-adrenergic receptor blockade attenuates ischemia in conscious dogs during exercise. AB - Studies on the role of alpha-adrenergic constrictor tone in the coronary vascular bed during ischemia were performed in dogs running on a treadmill. The animals were instrumented with a left ventricular pressure transducer, and regional systolic wall thickening (%WTh) was assessed by sonomicrometry in the anterior and posterior walls of the left ventricle. An intracoronary catheter was implanted chronically in the circumflex coronary artery, and a hydraulic cuff was placed proximally around the artery. After beta-adrenergic blockade with propranolol (0.8 mg/kg i.v.), acute stenosis of the coronary artery was performed during running in five dogs to induce severe regional myocardial dysfunction in the posterior wall. Intracoronary infusion of the selective alpha 2-adrenergic blocking agent idazoxan (80 micrograms/kg) improved %WTh in the ischemic region from 5.1 +/- 1.6 to 10.8 +/- 2.8% (p less than 0.05), without any significant effect on the anterior wall. Blood flow to the subendocardium of the posterior wall (radioactive microspheres) increased from 0.17 +/- 0.05 to 0.45 +/- 0.30 (ml/min)/g (p less than 0.05). It is concluded that in exercising dogs subjected to beta-adrenergic blockade, significant postjunctional alpha 2-adrenergic receptor-mediated coronary vasoconstriction exists, even during severe ischemia. Regional alpha 2-adrenergic receptor blockade can reduce regional ischemia and improve contractile function by attenuating exercise-induced sympathetic vasoconstriction in this conscious animal model. PMID- 2893670 TI - Bioassay of thyroid-stimulating immunoglobulin in cryopreserved human thyroid cells: optimization and clinical evaluation. AB - We have explored the method of Rapoport et al. (J Clin Endocrinol Metab 1984;58:332-8) for the bioassay of thyroid-stimulating immunoglobulin (TSI) in cultured human thyroid cells, to optimize the assay and to evaluate its utility in clinical diagnosis and management of patients with autoimmune thyroid disease. Here we describe the procedure ultimately adopted, its major properties, and the results it has yielded in various clinical states. Clinical sensitivity of the assay was established by demonstrating TSI activity in all of 60 cases of active Graves' disease. We observed in these patients a nonlinear correlation between concentrations of TSI and of triiodothyronine, as well as between TSI concentration and the clinical severity of the thyrotoxicosis. Specificity of the assay was demonstrated by finding no TSI bioactivity in 13 patients with toxic adenoma, five with cold nodule, and 18 of 19 with nontoxic goiter. Remission of Graves' disease in 25 patients was invariably accompanied by undetectable concentrations of TSI; evidently this assay may be useful in identifying patients who are likely to go into remission. TSI activity was present in eight of 11 patients with euthyroid ophthalmopathy (unilateral and bilateral) associated with a normal response to the thyrotropin-releasing hormone test and absence of increased titers of antithyroid antibodies, suggesting that this assay may provide a powerful tool in the clinical diagnosis of this disorder. PMID- 2893671 TI - The gamma-glutamyltransferase isoenzyme pattern in serum as a signal discriminating between hepatobiliary diseases, including neoplasias. AB - We have used the gamma-glutamyltransferase (GGT) isoenzyme pattern in serum as a means for discriminating between hepatobiliary diseases, including neoplasias. The reference pattern, determined in 142 normal subjects with a simplified conventional cellulose acetate electrophoretic procedure, contained two GGT bands, alpha 1-GGT and alpha 2-GGT, in proportions of 60-80% and 20-40%, respectively. Sera from 95 hepatobiliary patients showed typical isoenzyme features: (a) a beta-migrating GGT form that was less than 10% of the total GGT in chronic hepatitis and cirrhosis, and less than or equal to 30% of the total GGT in cirrhosis with intrahepatic cholestasis and in cases of extra- and intrahepatic obstructive jaundice, including liver neoplasias; (b) a gamma migrating GGT band and (or) a "dep-GGT" (nonmigrating) band in cases of extrahepatic jaundice; and (c) an albumin-migrating GGT band that had a diagnostic sensitivity of 75% for hepatic tumors. The diagnostic specificity of this last band is 92% toward other hepatic disorders and 91% toward nonhepatic neoplasias; we consider it a potential specific marker for primary or metastatic liver neoplasias. PMID- 2893672 TI - Improved procedure for measuring gamma-glutamyltransferase isoenzymes in serum. AB - In this electrophoretic procedure for measuring isoenzymes of gamma glutamyltransferase, patterns obtained are highly reproducible and the analytical imprecision (CV) ranges from 1.10% to 6.17%. A cellulose acetate support is used, at 220 V for 40 min. Sharply resolved isoenzyme bands were made visible by fluorescence scattered light, formed by use of a coumarin derivative as donor substrate. Two bands were observed for sera from normal subjects; four bands were variably present in sera from patients with different hepatobiliary diseases. Detection of the latter was satisfactory, down to a total activity in serum of 8 10 U/L. Three of the pathological bands were associated with low- and (or) very low-density lipoproteins, whereas a major fraction of one of the normal bands in cirrhotic sera precipitated with high-density lipoprotein. The bands in normal sera, and one of the abnormal bands, did not. PMID- 2893673 TI - Prevention of hypoglycaemia in a patient with pancreatic microadenomatosis by a long-acting somatostatin analogue SMS 201-995. AB - Acute suppression of insulin secretion from pancreatic insulinomas by long-acting somatostatin analogue SMS 201-995 has been documented. We report the chronic use of the drug in a patient with persistent hypoglycaemia due to benign pancreatic microadenomatosis with satisfactory control of plasma glucose level and reduction of insulin production. There was no tachyphylaxis or untoward side-effect noted during the 6-month treatment period. PMID- 2893675 TI - Genotyping of cystic fibrosis families with linked DNA probes. AB - Forty-six British families, containing at least one child affected with cystic fibrosis, were typed for restriction fragment length polymorphisms (RFLPs) by the probes pmet H, pmet D, pJ3.11 and 7c22. Thirty-five (76%) were fully informative for prenatal diagnosis and carrier detection, while in the remainder prenatal exclusion of an affected fetus could be carried out in half the pregnancies. The frequencies of individual alleles did not differ between cystic fibrosis and normal chromosomes. However, the previously noted excess of one haplotype on chromosomes carrying the cystic fibrosis gene was confirmed. PMID- 2893674 TI - Gamma-glutamyl transferase activity in the amniotic fluid of fetuses with chromosomal aberrations and inborn errors of metabolism. AB - The activity of gamma-glutamyl transferase (GGT) was measured in amniotic fluid collected between the 16th and 30th weeks of gestation from 81 pregnancies with fetuses affected by chromosomal aberrations, nine with different types of inborn errors of metabolism, two with hemophilia A and one with fragile X syndrome. The GGT activity was compared with that from 1000 normal pregnancies and deliveries resulting in healthy newborns. Contamination of amniotic fluid by blood did not affect the GGT activity. Pathologically decreased activity was found in 25 of 56 amniotic samples from pregnancies with fetal autosomal chromosomal aberrations (44.6%). It was decreased in 15 of 35 pregnancies with fetal trisomy 21 (43%), in 11 of 19 pregnancies with fetal trisomy 18 (58%), in one of three pregnancies with fetal trisomy 13 and in two pregnancies with fetal trisomy 8 and triploidy, respectively. In only three of 16 pregnancies with fetal sex chromosomal aberrations was the GGT activity low. Increased GGT activity was found in three of six pregnancies with unbalanced structurally rearranged karyotypes of the fetuses. Normal GGT activity was observed in all nine amniotic fluid samples from pregnancies with fetuses affected with different forms of inborn errors of metabolism diseases, in the two pregnancies with hemophilia A and in the pregnancy with a male fetus with fragile X syndrome. These and earlier findings indicate that the GGT activity in amniotic fluid is mostly decreased in pregnancies with severe fetal developmental abnormalities, such as autosomal chromosomal aberrations, which could possibly be secondary to an alteration of the microvillar transport system of GGT to the amniotic fluid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893676 TI - (+/-)-Pindolol has beta 2-adrenoceptor antagonist but not agonist action on the costo-uterine muscle of the rat. AB - 1. The effects of isoprenaline and (+/-)-pindolol on rat isolated costo-uterine muscle have been compared. 2. Isoprenaline produced reproducible concentration dependent inhibition of contractions, and maximal doses (less than 0.1 mumol/l) produced mean inhibition of 87, 94 and 97% of field, carbachol and potassium stimulated preparations, respectively. 3. (+/-)-Pindolol, when effective, produced inhibition only in concentrations greater than its pA2 value (9.87) as an antagonist of isoprenaline; mean maximal effects were less than 60% of those produced by isoprenaline. 4. It is concluded that (+/-)-pindolol is a potent antagonist, but has only variable agonist action, at the beta 2-adrenoceptors of the rat costo-uterine muscle. PMID- 2893677 TI - Pharmacological properties of the atropine-resistant contraction of the carp (Cyprinus carpio) intestinal bulb induced by transmural stimulation. AB - 1. The pharmacological properties of the atropine-resistant contraction of the carp intestinal bulb induced by transmural stimulation were investigated. 2. In the presence of atropine (1 microM), transmural stimulation caused frequency dependent (2-50 Hz) contraction which was abolished by tetrodotoxin (780 nM). 3. The atropine-resistant contraction was not decreased by tubocurarine (5 microM), hexamethonium (100 microM), carteolol (5 microM) and phentolamine (5.4 microM). 4. In vitro pretreatment with guanethidine (10 microM for 1 hr) markedly decreased the noradrenaline and adrenaline contents of the carp intestinal bulb. The atropine-resistant contraction was not affected by pretreatment with guanethidine. 5. Diphenhydramine (1 microM), methysergide (3 microM) and naloxone (1 microM) did not decrease the atropine-resistant contraction, indicating that histamine, 5-hydroxytryptamine and opioid peptides were not involved in the atropine-resistant response. 6. These results indicate that a non-cholinergic, non-adrenergic excitatory nerve is present in the carp intestinal bulb. The neurotransmitter mediating the excitatory response could not be identified. PMID- 2893678 TI - Receptor turnover and the action of 5-hydroxytryptamine on the salivary glands of the blowfly Calliphora erythrocephala, the housefly Musca domestica and frog skin epithelium. AB - 1. Continual stimulation of frog skin epithelium and the salivary glands of the insects Calliphora and Musca with 5-hydroxytryptamine (5-HT) leads to desensitisation, i.e. the tissue fails to respond to the application of further 5 HT. 2. Incubation of desensitised frog skin and Musca salivary glands with either N-acetyl neuraminic acid or inositol partially restored the 5-HT responses whilst incubation with a combination of N-acetyl neuraminic acid and inositol gave additive effects on the recovery of the 5-HT responses. 3. Incubation of desensitised salivary glands of Calliphora with inositol totally restored the 5 HT response whilst incubation with N-acetyl neuraminic acid had no effect. 4. It is concluded that desensitisation involves depletion of secondary messenger from the tissues coupled with receptor degradation and that considerable differences exist in the turnover of 5-HT receptors, the receptors in Musca salivary glands being highly labile, those in Calliphora salivary glands highly stable and those of frog skin epithelium being intermediate in their stability. PMID- 2893679 TI - Autonomic effects on protein secretion by rat submandibular salivary glands. AB - 1. Following treatment with cholinergic and beta-adrenergic drugs, the beta-type protein, associated with cAMP, was secreted regardless of the doses used. 2. Following treatment with alpha 1-adrenergic drugs, both the beta-type and alpha type proteins were secreted depending on the doses used and the alpha-type protein was completely converted to the beta-type with alpha-blockers. 3. Following treatment with alpha 2-adrenergic drugs, the gamma-type protein, associated with cGMP, was secreted independent of the doses used. PMID- 2893680 TI - Acute hyperbilirubinaemia in rainbow trout (Salmo gairdneri) caused by resin acids. AB - 1. The effects of resin acids on the development of, and recovery from jaundice in rainbow trout were studied. 2. At 0.4 mg/l or higher resin acid concentration, fish developed jaundice in 2-4 days at water temperatures over 17 degrees C and recovered from severe intoxication within 6 days. 3. Jaundice results at least partially from insufficient secretion of conjugated bilirubin into the bile, probably because resin acids and bilirubin share a common secretion pathway. 4. The activity of liver UDP-glucuronosyltransferase and concentration of plasma bilirubin are sensitive indicators of the exposure of trout to discharges containing resin acids. PMID- 2893681 TI - Phenobarbital: a locus of action on spike broadening and potassium inactivation. AB - 1. The effect of phenobarbital on frequency-dependent spike broadening and potassium inactivation was studied in snail neurons. 2. The amount of spike broadening was significantly depressed by the application of 10(-3) M phenobarbital but the time course of broadening was unaffected. 3. In voltage clamped neurons, this concentration of phenobarbital significantly depressed the amount of potassium current inactivation without altering its time constant. 4. A possible locus of phenobarbital's anticonvulsant action is through a decrease in synaptic efficacy resulting from a depression of presynaptic spike broadening. PMID- 2893683 TI - Comparative studies on nerve- and noradrenaline-induced melanosome aggregation within different species of fish. AB - 1. The aggregation of melanosomes within melanophores of the cuckoo wrasse (Labrus ossifagus; belonging to the family Labridae) has, on pharmacological grounds, been shown to be mediated by postsynaptic alpha 2-adrenoceptors which in turn act via an inhibitory control of adenylate cyclase. 2. In the present paper we have investigated some American species belonging to the Labridae, Haemulidae, Embiotocidae, Clinidae and Pleuronectidae. 3. In all instances, except in the case of sargo (Haemulidae), we could demonstrate that melanosome aggregation probably was mediated by postsynaptic alpha 2-adrenoceptors which mediate their effect by inhibiting the adenylate cyclase of the melanophores. 4. Although these receptors apparently, on pharmacological grounds, may be classified as alpha 2 adrenoceptors it was also concluded that there is a phylogenetic divergence among these receptors. PMID- 2893682 TI - Responses of the three-toed sloth, Bradypus tridactylus, to some commonly used pharmacologic agents. I. Autonomic drugs. AB - 1. Sloths are very responsive to epinephrine and norepinephrine; i.v. injection of 1 microgram/kg elevates systolic pressure 80 and 90% respectively. 2. Doses as low as 0.01 microgram/kg of epinephrine as well as norepinephrine raise diastolic pressure. 3. Similarity of effects of these catecholamines can be explained on the basis of the low proportion of skeletal muscle (35 vs 45% in most mammals) and a small liver which reduces the proportion of beta 2 dilators to alpha constrictors responding to epinephrine. 4. Slowness of reflexes allows clear separation of early (0-20 sec), direct accelerating heart rate effect (up 15% with 1 microgram/kg of norepinephrine) and later (20-60 sec), reflex bradycardia (down 30% from control level). 5. Sloths are more sensitive to the vasodilating effects of isoproterenol or less sensitive to beta 1 cardiac stimulating effects than most laboratory mammals; doses as low as 0.1 microgram/kg cause a fall in mean arterial pressure not overcome by increased heart rate. PMID- 2893684 TI - Interactions of organic pollutants with gills of the bivalve molluscs Anodonta californiensis and Mytilus californianus: uptake and effect on membrane fluxes. II. AB - 1. The uptakes of 2,4,5-T, glyphosate, parathion, paranitrophenol, naphthalene, glycine, and inulin by gills of the bivalve molluscs Anodonta californiensis (freshwater) and Mytilus californianus (marine) show non-polar compounds are taken up to a greater extent than polar compounds except where active transport occurs. 2. The uptake of glycine by M. californianus is reduced by pollutants containing complexing functional groups but not by non-polar compounds. 3. The uptake of parathion alters the polyphosphate-inorganic phosphate balance in M. californianus. 4. The uptakes of pollutants parallel their toxicities toward rats. PMID- 2893686 TI - Effects of synthetic peptides on giant neurones identified in the ganglia of an African giant snail (Achatina fulica Ferussac). IV. AB - 1. The previous papers (Ku et al., 1986; Kim et al., 1987; Yongsiri et al., 1987) reported the effects of the synthetic peptides, i.e. Met-enkephalin, substance P, neurotensin, oxytocin, Arg-vasopressin, proctolin, FMRFamide, ranatensin C etc., on about 20 identifiable giant neurones of an African giant snail (Achatina fulica Ferussac). 2. In the present study, the effects of the same peptides on the following Achatina neurones, other than those of the previous papers, were investigated: v-RPLN, v-LPSN, v-VNAN, v-VLN, r-VMN, l-VMN, v-l-VOrN and d-RCDN. 3. Of the neurones tested here, v-RPLN (ventral-right parietal large neurone) was excited slightly by Met-enkephalin, excited markedly by oxytocin, and inhibited by FMRFamide, at 10(-4) M. 4. Of these effects, those of oxytocin and FMRFamide were undoubtedly the direct effects on the neurone tested, whereas those of Met enkephalin were probably due to the synaptic activations. 5. Another neurone, v LPSN (ventral-left parietal large neurone), was affected by oxytocin and ranatensin C at 10(-4) M. The two substances sometimes showed similar simple excitatory effects, in other cases biphasic (excitation followed by inhibition) effects, and in a few cases almost no effect. 6. The rest of the neurones tested were not sensitive at all to any of the peptides examined. PMID- 2893685 TI - Caffeine effects on buccal muscles of Aplysia. AB - 1. Caffeine (35-70 mM) elicited contractions of Aplysia buccal muscle El. In a Ca2+-free medium, in which ACh-elicited contractions rapidly fail, caffeine elicited contractions of approximately the same size as in normal medium. 2. 5-HT (10(-8) M and 10(-7) M) did not enhance caffeine-elicited contractions. 3. Lower concentrations (1-10 mM) of caffeine inhibited ACh-elicited contractions. Caffeine (7 mM) reduced the contraction by 80%. 4. Caffeine (7 mM) reduced ACh elicited depolarization by 60%. 5. Caffeine (7 mM) increased 45Ca2+ influx into Aplysia buccal muscle I5. The stimulation of influx of 45Ca2+ by 10(-3) M ACh was non-additive with the stimulation caused by caffeine, and 7 mM caffeine reduced the influx caused by 10(-3) M ACh. PMID- 2893687 TI - Effects of temperature and general anesthesia on the water gain and the inulin space of the brain of the toad, Bufo arenarum Hensel. AB - 1. The water gain in vitro and the inulin space of the brain of the toad were measured under different experimental conditions. 2. There exists a highly positive correlation between water uptake by the brain and the acclimation incubation temperature, 7 degrees-37 degrees C. 3. Regional differences in the water gain and inulin space were also demonstrated when measured at 20 degrees C. Higher gains were observed in hemispheres, mesodiencephalon and rhombencephalon. 4. The water gain was higher for whole brains obtained under deep anesthesia with ether or urethane but not under nembutal. The inulin space was also higher under ether but lower under urethane. Nembutal had no effect in this case either. 5. A hypothesis about the possible role of water and electrolyte movements in the mechanism of action of some general anesthetics is advanced. PMID- 2893688 TI - Octopamine action on the contractile system of crustacean skeletal muscle. AB - 1. In the opener muscle of walking legs of crayfish (Astacus leptodactylus) octopamine (OA) greatly enhances the contractions resulting from brief applications of L-glutamate or of elevated K-concentrations. Synephrine is as effective as OA. 2. In the case of potentiation of responses to high-K applications a presynaptic component of the OA action was excluded by first desensitising the muscle fibres to the action of the natural transmitter, using a high concentration (1 mM) of glutamate. 3. The Ca-antagonists Co, Ni and Mn (1 mM) reduced the effects of glutamate and of elevated K to about one-half. In preparations treated with OA, the same Ca-antagonists also depressed the potentiated contractural responses to glutamate and to elevated K, again to about one-half. 4. OA also enhanced contractions resulting from the application of caffeine. 5. With 5-hydroxytryptamine (5-HT) application, the same postsynaptic effects were obtained as described for OA, except that the 5-HT actions were much weaker. 6. With OA, maximal effects were obtained with concentrations of 5 x 10( 6)-10(-5) M; maximally effective concentrations of 5-HT were around 10(-5) M. 7. The lowest effective concentrations of OA were around 10(-8) M; those of 5-HT were around 10(-7) M. 8. In the same preparation, 5-HT is far more effective in enhancing transmitter release (presynaptic action) than OA, the lowest effective concentration being around 10(-11) M while no presynaptic effects of OA were seen at concentrations below 10(-8) M, in some cases even below 10(-5) M. PMID- 2893689 TI - Relapse in delusional depression: a retrospective study of the course of treatment. PMID- 2893690 TI - Altered tyrosine and tryptophan metabolism during hypothermic hibernation in the 13-lined ground squirrel (Spermophilus tridecemlineatus). AB - (1) Tyrosine and tryptophan metabolism in brain and peripheral tissues were studied in hypothermic hibernating and normothermic nonhibernating 13-lined ground squirrels (Spermophilus tridecemlineatus). (2) In the hypothermic hibernating state, there were significant elevations of brain stem tyrosine, norepinephrine, and dopamine levels; forebrain norepinephrine and dopamine levels; and cerebellum norepinephrine and tyrosine levels. (3) On the other hand, plasma norepinephrine levels were significantly decreased in hypothermic hibernating squirrels while plasma tyrosine levels were increased. Kidney norepinephrine levels were significantly increased in hypothermic hibernating squirrels, while kidney tyrosine levels were decreased. Total plasma tryptophan and free plasma tryptophan were significantly reduced in hypothermic hibernating squirrels. Hepatic tyrosine aminotransferase Km and Vmax were decreased in hypothermic hibernating squirrels, while tryptophan 2,3-dioxygenase activity was not altered. Plasma and liver albumin were increased in hypothermic hibernating squirrels, while plasma and liver total protein were not altered. (4) These results demonstrate that significant changes in tyrosine and tryptophan metabolism occur in both central and peripheral tissues with concomitant alterations in metabolites during hypothermic hibernation in 13-lined ground squirrels. PMID- 2893691 TI - Appetite in anorexia of cancer. PMID- 2893692 TI - Adverse reactions in the skin from anti-hypertensive drugs. AB - Anti-hypertensive drugs, including diuretics and beta-blocking drugs, belong to a group of therapeutics used by about a fourth of the Danish population. As with cytostatics, antibiotics, and topical remedies, they rather frequently cause adverse drug reactions (ADR) in the skin. No exact statistical information is available concerning the extent of such side effects. The information obtained by Danish National Board of Health's Committee on Adverse Drug Reactions shows that 10-60% of ADR from diuretics, beta-blocking agents, and anti-hypertensive drugs are dermatological. The skin symptoms are not unique for any specific drug. But certain symptoms occur more frequently than others. Thiazides can give vasculitis, a phototoxic/-allergic eruption, erythema multiforme, or eczema. The combination of amiloride (5 mg) and hydrochlorothiazide (50 mg) carries the highest number of recorded ADR; 59% of these are in the skin. Half of the skin ADR are phototoxic eczema. Furosemide may give eczema, purpura, a bullous eruption, or Steven-Johnson's syndrome in rare cases. Methyldopa can induce eczematous eruptions on hands and feet, a lichenoid eruption, a lupus erythematosus-like eruption, or purpura. Hydralazine may give lupus erythematosus like eruptions, eczema, or urticaria. Non-specific beta-blocking drugs can induce a morbilliform rash and may aggravate psoriasis. Captopril may induce pruritus in up to 15% of the patients and skin eruptions in 2%. The most serious dermatological side effect, exfoliative dermatitis, is very rarely seen following the use of anti-hypertensive drugs or diuretics. PMID- 2893694 TI - [Plasma osmotic pressure in patients with epidemic hemorrhagic fever]. PMID- 2893693 TI - Nucleotide sequences and unusual electrophoretic behavior of the W chromosome specific repeating DNA units of the domestic fowl, Gallus gallus domesticus. AB - Nucleotide sequences of three independently cloned repeating units of the W chromosome-specific repetitive DNA sequences ("XhoI family") of the chicken were determined. All three units are 717 bp long with XhoI sites at both ends. There are only 21 sites out of 717 bases where a single base change occurs in one of the three clones. Each of these repeating units consists of 34 tandem repeats of about 21 bp. Sequences of some members of these internal repeats are not well conserved, but the majority of the repeats are characterized by the presence of (A)3-5 and (T)3-5 clusters separated by 6-7 relatively G + C-rich base pairs. One striking feature of the cloned 717 bp repeating units is that they migrate unusually slowly on electrophoresis in polyacrylamide gels. The same feature is also shown by a genomic population of the 0.7 kb repeating units recovered from XhoI digests of the genomic DNA of the female chicken. This anomalous behavior is attributed to the occurrence of DNA curvatures because of the above sequence characteristics and partial recovery of the electrophoretic mobility in the presence of distamycin A. Another feature of the 717 bp repeating unit is the presence of 438 and 159 nucleotide-long open reading frames (ORFs) at each end of the unit. A possible function of the XhoI family sequences in the heterochromatization of the W chromosome and the significance of the ORFs are discussed. PMID- 2893695 TI - Pancreatic A- and D-cell response to arginine during acute alloxan-induced intra islet insulinopenia. AB - This study was performed to investigate the role of pancreatic B-cell function on glucagon and somatostatin response to arginine. Isolated perfused rat pancreas was used for the experiment. Acute B-cell destruction was induced in vitro by 0.56 mM alloxan infused directly into the vascular system of the perfused pancreas. This resulted in a fall in basal insulin release and in a complete absence of hormone response to 20 mM arginine. Glucagon and somatostatin release during metabolic stimulus was superimposable on that observed in the control experiments (no alloxan infusion). We conclude that a normal B-cell function is not required for glucagon and somatostatin response to arginine. PMID- 2893696 TI - The disposition and pharmacokinetics of ketoconazole in the rat. AB - The disposition, biliary excretion, and pharmacokinetics of ketoconazole in Sprague-Dawley rats were determined after intravenous administration. Greater than 80% of the radioactivity after a 5 mg/kg iv dose of 3H-ketoconazole was excreted in the feces. Urinary excretion was essentially complete after 48 hr; however, fecal excretion was prolonged over a 7-day period. Biliary excretion of radioactivity averaged 54.3 +/- 18.0% of the dose over a 7.5-8-hr period in pentobarbital-anesthesized rats. The possibility of enterohepatic recirculation was examined using a linked rat technique. Less than 2% of the radioactivity was found in the recipient bile over 9-12 hr. In eight male rats, the plasma pharmacokinetics of ketoconazole, as determined by an HPLC assay with fluorescence detection, were as follows: VD = 655 +/- 91 ml/kg, Cl = 14.4 +/- 5.1 ml/min/kg, and t 1/2 = 35.0 +/- 12.3 min. Three of the rats were given an additional oral dose to determine absolute bioavailability. The time to peak was 30-60 min, and the bioavailability was 35.8 +/- 3.55%. Previous studies have indicated that ketoconazole is well absorbed in rats; therefore, the poor bioavailability is probably due to first pass metabolism. The prolonged fecal excretion of radioactivity from an intravenous dose was probably caused by slow elimination of ketoconazole metabolites. PMID- 2893697 TI - Metabolism and disposition of cyproheptadine and desmethylcyproheptadine in pregnant and fetal rats. AB - The tissue distribution of unchanged drug and metabolites in pregnant rats was studied following oral administration of cyproheptadine (CPH) or its N demethylated metabolite, desmethylcyproheptadine (DMCPH). A high performance liquid chromatographic (HPLC) method was developed for analysis of CPH and its metabolites in maternal and fetal tissues. In pregnant rats given CPH (11 mg/kg) during the final 2 or 8 days of gestation, the unchanged drug, DMCPH and desmethylcyproheptadine-10,11-epoxide (DMCPH-epoxide) were detected in various maternal and fetal tissues, including pancreas, liver, lung, kidney and placenta. DMCPH and DMCPH-epoxide were also present in fetal tissues after 8 oral doses of DMCPH (11 mg/kg) to pregnant rats. Tissue concentrations of unchanged CPH and its metabolites, after each treatment regimen, were highest in the lung. Except for pancreas and brain, the levels of CPH, DMCPH, or DMCPH-epoxide in tissues at early times after completing CPH treatment were 3- to 10-fold higher in the dam than in the fetus. Brain levels of CPH metabolites were higher in the fetus than in the maternal animal. The metabolite DMCPH-epoxide appeared in fetal pancreas in concentrations equal to those in the maternal pancreas. In separate experiments designed to examine the metabolic capability of the fetus (day 20 of gestation), it was found that fetally administered CPH was not demethylated and, instead, epoxidated to form cyproheptadine-10,11-epoxide (CPH-epoxide). Administration of the metabolite DMCPH to the fetus showed that it was also readily converted to an epoxide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893699 TI - Metabolite profile in milk of lactating rats after treatment with a carcinogen, N 2-fluorenylacetamide. AB - Metabolites were determined in milk and urine of lactating rats 4 to 5 hr after each of 3 to 6 ip injections of N-2-fluorenylacetamide (2-FAA) at 0.2 mmol/kg of body weight. Milk contained 2-FAA as the major free compound, variable amounts of N-2-fluorenamine (2-FA) and phenols (7- greater than 5- greater than 3-hydroxy-2 FAA) chiefly as glucuronides, and very small amounts of the glucuronide of N hydroxy-2-FAA. Urine contained large amounts of the phenols and N-hydroxy-2-FAA as free and conjugated compounds, but in contrast to milk, only small amounts of 2-FAA and no 2-FA. Pretreatment of rats with beta-napthoflavone, an inducer of microsomal C- and N-hydroxylations of 2-FAA, increased the amounts of 3- and 5 hydroxy-2-FAA in milk and of 3-hydroxy-2-FAA in urine. However, the total amounts of the compounds excreted in 1 ml of milk or urine, i.e. 0.05 to 0.13% or 0.6% of the dose of 2-FAA, respectively, were similar in the uninduced and induced groups. Protein hydrolysates of milk of 2-FAA-treated rats and of milk interacted with 2-nitrosofluorene (2-NOF) in vitro both contained 2-FA and 9-oxo-2-FA. This suggested formation of 2-NOF in vivo possibly by peroxidative metabolism of N-OH 2-FAA. Since 2-NOF has been reported to form adducts with unsaturated lipids, the effect of treatment of lactating rats with 2-FAA on the fatty acid composition of milk lipids was examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893701 TI - Pharmacokinetics and metabolism of the antitumor drug amonafide (NSC-308847) in humans. AB - Pharmacokinetics and urinary excretion of Amonafide (5-amino-2-[2 (dimethylamine)ethyl]-1H-benz[de]isoquinoline-1,3-(2H)- dione) were examined in seven patients who were administered 400 mg/m2 of drug as a 30-min infusion on a daily schedule for 5 consecutive days. Amonafide concentrations in plasma and urine were determined using reversed phase HPLC. Amonafide was eliminated from plasma with a terminal half-life of 3.5 hr. Renal excretion accounted for 23% of the administered dose. Amonafide pharmacokinetic parameters after the initial dose (day 1) were similar to those calculated after the fifth daily dose. Amonafide undergoes a significant amount of metabolism and eight urinary metabolites have been identified using a thermospray liquid chromatography-mass spectrometry (LC/MS) technique. Various N-acetylated species appear to be the major metabolites, although no evidence of N-acetylation was found in urine obtained from two patients. Two of the primary metabolites, the N(N5)-acetyl and N'(N1)-oxide metabolites of Amonafide, were tested in vitro for cytotoxicity against P388 murine leukemia cells. In this test system, the N-acetyl metabolite was observed to be only slightly less cytotoxic than the parent compound. The N' oxide of Amonafide, however, proved to be inactive. These results are discussed together with the pharmacokinetic and metabolism data of this new investigational antitumor drug. PMID- 2893700 TI - Species-dependent enantioselective glucuronidation of three 2-arylpropionic acids. Naproxen, ibuprofen, and benoxaprofen. AB - The enantioselective glucuronidation of several racemic 2-arylproprionic acids (naproxen, ibuprofen, and benoxaprofen) was investigated in vitro with immobilized microsomal protein from human, rhesus monkey, and rabbit liver as the source of UDP-glucuronyl-transferases. Human microsomes, solubilized microsomal protein, and immobilized protein all gave comparable enantioselectivity. The diastereomeric glucuronides were separated and quantitated by HPLC and characterized stereochemically by co-elution with glucuronides formed from authentic resolved enantiomers. Conjugation of the carboxylic acid moieties occurred stereoselectively with all three substrates. However, enantioselectivity varied qualitatively and quantitatively with substrate as well as with species. The glucuronidation of (S)-naproxen by human liver enzymes was inhibited in the presence of (R)-naproxen and vice versa. The ratio of the glucuronides of (S) benoxaprofen to that of (R)-benoxaprofen in rhesus monkey urine varied between individual animals and appeared to change through time as dosing continued. Hydrolysis of the diasteriomeric glucuronides of (R)- and (S)-naproxen was differentially inhibited by addition of 1,4-saccharolactone. PMID- 2893698 TI - Effects of model traumatic injury on hepatic drug metabolism in the rat. VI. Major detoxification/toxification pathways. AB - A previously validated small mammal trauma model, hindlimb ischemia secondary to infrarenal aortic ligation in the rat, was utilized to investigate the effects of traumatic injury on two of the major hepatic enzymes of detoxification, glutathione S-transferase and epoxide hydrolase. Hepatic cytosolic glutathione S transferase activity toward a variety of substrates showed a 26-34% decrease at 24 hr after model injury. Hepatic microsomal epoxide hydrolase activity toward 1,2-epoxy-3-(p-nitrophenoxy)propane was diminished by 53% after model trauma. Both enzymatic activities toward styrene oxide were similarly depressed. The toxicological sequelae of these derangements were illustrated by administering a dose of styrene oxide (300 mg/kg, ip) which was below the threshold dose (350 mg/kg, ip) necessary to produce hepatotoxicity in control animals. Model trauma dramatically enhanced the hepatotoxic effects of the subthreshold dose, as well as the covalent binding of labeled styrene oxide to liver proteins. These findings indicate that traumatic injury renders the animal more susceptible to agents which are detoxified by glutathione S-transferase and epoxide hydrolase. Conversely, model trauma provided almost complete protection from the hepatotoxic effects of a standard dose (200 mg/kg, ip) of bromobenzene. This protection appeared to derive from a post-traumatic alteration of cytochrome P-450 subpopulations that decreased the formation of the potentially toxic 3,4-epoxide metabolite, despite an increase in the cytochrome P-448-mediated generation of the nontoxic 2,3-epoxide. For bromobenzene, the change in cytochrome P-450 mediated activation appeared quantitatively more significant in overall toxicity than the post-traumatic depression of detoxification pathways described above, leading to decreased toxicity in vivo. For other compounds, the combination of post-traumatic influences on cytochrome P-450/P-448 activity and epoxide hydrolase/glutathione S-transferase activities could lead to markedly enhanced toxicity. PMID- 2893702 TI - Disposition, pharmacokinetics, and metabolism of a dermal dose of [14C]2,5 hexanedione in hens. AB - A dermal dose of 50 mg/kg (7.5 microCi/kg) of [14C]2,5-hexanedione (2,5-HD) was applied on a protected area on the backs of hens. Five groups of three hens were killed after 4, 8, 24, 36, and 48 hr. 2,5-HD disappeared monoexponentially from the application site with a half-life of 6 hr. After 48 hr, 35% of the radioactivity was expired as volatile material, largely as 2,5-HD. The combined urinary fecal excreta accounted for 15% of the eliminated radioactivity, while the 14CO2 accounted for 11.9% of the radioactive dose. The highest concentration of 14C was detected in the bile. Among tissues analyzed, liver and kidney contained the highest concentrations of radioactivity, whereas the brain, spinal cord, and peripheral nerves showed smaller concentrations. The half-lives for the elimination of 14C were longest for muscle (71 hr) and shortest for adipose tissue (12 hr), while the remaining tissues showed half-lives ranging from 20 to 30 hr. Radioactivity in the plasma reached a peak at 4 hr. Most of this radioactivity was identified as 5-hydroxy-2-hexanone followed by 2,5-HD and 2,5 dimethylfuran; these chemicals then disappeared biexponentially with terminal half-lives of 7.6 hr, 12.6 hr, and 28.6 hr, respectively. 2,5-HD was the most accounted chemical found in the liver, lung, and kidney, while 5-hydroxy-2 hexanone was found to be most abundant in the combined urinary-fecal excreta. PMID- 2893704 TI - The pharmacokinetics of pentane, a by-product of lipid peroxidation. AB - Pentane excretion in breath has been used as an index of lipid peroxidation in intact animals based on the premise that the hydrocarbon is metabolically inert. However, it is now known that pentane is metabolized by animals and that its pulmonary excretion is affected both by its production and by its metabolism. Thus, changes in pentane metabolism could obscure alterations in the rate of production, which is the quantity most closely related to the extent of lipid peroxidation. The purpose of this study was to determine the clearance of pentane from arterial blood by the rat following an injection of the hydrocarbon into a closed chamber containing the animal. Clearance was estimated from the analysis of arterial blood and chamber air concentration-time curves using a three compartment model which included the chamber as a peripheral compartment. The required blood-to-air partition coefficients were determined experimentally. Blood clearance values obtained from control rats, rats pretreated with carbon tetrachloride, and animals given 4-methylpyrazole were 0.141, 0.021, and 0.014 liter/min/kg, respectively. The 85% decrease in clearance of animals pretreated with either a metabolic inhibitor or a toxin which destroys cytochrome P-450 suggests that metabolism may contribute significantly to the overall elimination of pentane. Therefore, the quantitation of pentane excretion rate as an index of lipid peroxidation should include a consideration of possible changes in metabolic clearance. PMID- 2893703 TI - Monooxygenase-mediated activation of chlorotrianisene (TACE) in covalent binding to rat hepatic microsomal proteins. AB - Chlorotrianisene is a therapeutic estrogen and contaminant of the pesticide methoxychlor. Incubation of [3H]chlorotrianisene with rat liver microsomes, supplemented with NADPH, yielded covalent binding of radiolabeled metabolite(s) to microsomal components. This binding was dramatically stimulated when microsomes from methylcholanthrene-treated rats were used. However, microsomes from phenobarbital-treated animals did not enhance binding. Analysis of solubilized microsomes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed radiolabeled bands in the 45- to 66-kDa range. Furthermore, these bands were sensitive to protease degradation, indicating that the recipient macromolecules were proteins and possibly cytochrome P-450(s). Selective inhibition of binding to microsomes prepared from control, phenobarbital-, and methylcholanthrene-treated rats by inhibitors of monooxygenase activity [beta-diethylaminoethyl diphenylpropylacetate (SKF-525A) and metyrapone], by alternate substrates (ethylmorphine and benzo[a]pyrene), and by oxygen exclusion indicated that the binding was dependent upon monooxygenase activity and that a specific P-450 may be involved. Compounds containing free sulfhydryls markedly inhibited covalent binding, suggesting that the reactive intermediate is an epoxide or a free radical. The epoxide hydratase inhibitor (1,1,1-trichloropropane oxide) failed to enhance covalent binding, suggesting that an epoxide of chlorotrianisene was not the reactive intermediate. By contrast, free radical scavengers (propyl gallate, N,N'-diphenylenediamine, and ascorbic acid) markedly inhibited covalent binding, indicating that binding was mediated via a free radical. Since both methylcholanthrene and phenobarbital did not enhance demethylation of chlorotrianisene and methylcholanthrene increased covalent binding, it appears that demethylation products are not involved in covalent binding or that demethylation is not the rate-limiting step. A possible pathway for the metabolism and covalent binding of chlorotrianisene is presented. PMID- 2893706 TI - N-oxidation of N-methylpyrrolidine released in vivo from cefepime. AB - Cefepime (BMY-28142), 7-[alpha-(2-aminothiazol-4-yl)-alpha-(Z)-methoximin oacetamido] -3-[(1-methyl-1-pyrrolidino)-methyl]-3-cephem-4-carboxylate is a potent cephalosporin that is unique in having a quaternized N-methylpyrrolidino side chain. Degradation of the beta-lactam ring can result in release of N methylpyrrolidine (NMP), an alicyclic tertiary amine. After iv bolus administration of [methyl-14C]NMP, most radioactivity in the urine of rats and a dog was present as a polar, nonextractable metabolite, which was isolated and identified as NMP N-oxide. A minor urinary metabolite was not identified. The NMP concentration in plasma declined in a rapid monoexponential manner, and there was a concomitant increase in the N-oxide concentration. After iv administration of cefepime, which was labeled with 14C in the methyl group of the NMP side chain, 86% of the radiolabel recovered in the urine was attributable to intact antibiotic. The balance was principally present as the N-oxide. Oxidation of NMP to the N-oxide by rat and human liver microsomes was demonstrable in vitro. These results indicate that intravenously administered NMP or NMP arising from the degradation of cefepime in vivo is subject to rapid metabolic clearance. PMID- 2893705 TI - Co-oxidation of 2-bromohydroquinone by renal prostaglandin synthase. Modulation of prostaglandin synthesis by 2-bromohydroquinone and glutathione. AB - Homogenates from rat renal papillae, a rich source of the prostaglandin (PG) H synthase system (PHS), metabolized [14C]2-bromohydroquinone, in the presence of arachidonic acid, to products which are covalently bound to protein. The co oxidation of 2-bromohydroquinone caused a concentration-dependent stimulation in 6-keto-PGF1 alpha, thromboxane B2, PGF2 alpha, PGE2, and PGD2 formation. Glutathione (1 mM) caused a decrease in prostaglandin formation and inhibited the arachidonic acid-supported covalent binding of [14C]2-bromohydroquinone with the concomitant formation of [14C]2-bromohydroquinone-glutathione conjugates, oxidized glutathione, and an increase in the recovery of [14C]2 bromohydroquinone. NADPH also inhibited [14C]2-bromohydroquinone covalent binding, probably by reduction of the semiquinone radical back to the hydroquinone. Indomethacin and aspirin, inhibitors of the cyclooxygenase component of PHS, and propylthiouracil and methimazole, inhibitors of the hydroperoxidase component of PHS, inhibited the arachidonic acid-supported covalent binding of [14C]2-bromohydroquinone by 94%, 52%, 78%, and 79% respectively. These data suggest that 1) renal PHS may play a role in activating the nephrotoxin, 2-bromohydroquinone, and that 2) xenobiotic metabolism and its subsequent effects on glutathione levels can modulate renal prostaglandin synthesis. PMID- 2893707 TI - Isolation and characterization of 4'-hydroxy T-2 toxin, a new metabolite of the trichothecene mycotoxin T-2. AB - Biotransformation of the trichothecene mycotoxin T-2 by the hepatic S-9 fraction prepared from phenobarbital-treated rats yielded a new metabolic product designated RLM-3. The metabolite was purified from the hepatic preparation using preparative HPLC. The structural analysis of RLM-3 was carried out using gas chromatography/mass spectrometry and 1H and 13C NMR. RLM-3 was identified as 4' hydroxy T-2. The toxicity of RLM-3 in comparison to T-2 toxin and 3'-hydroxy T-2 was assessed using a rat skin bioassay technique. The metabolite 4'-hydroxy T-2 was shown to be deacylated at the C-4 position to yield 4'-hydroxy HT-2 when incubated with rat hepatic S-9 preparations. PMID- 2893708 TI - Metabolism and excretion of dinitrobenzenes by male Fischer-344 rats. AB - All three dinitrobenzene (DNB) isomers cause methemoglobinemia, but only 1,3-DNB produces testicular toxicity in rats. In order to determine whether major differences exist in the routes of DNB metabolism, male Fischer-344 rats were given an oral dose (0.15 mmol/kg) of 14C-labeled 1,2-, 1,3-, or 1,4-DNB, and excreta were collected over 48 hr. Elimination of radiolabel was rapid; 85%, 60%, and 75% of the 1,2-, 1,3-, and 1,4-DNB dose was recovered in 24 hr, respectively. Urine was the primary route of excretion, accounting for 82% of the total dose of 1,2-DNB and 75% of the dose of 1,4-DNB after 48 hr. Radiolabel from 1,3-DNB was excreted to a slightly lesser extent in the urine (63% of the dose). A greater portion of radiolabel was excreted in the feces than with the other isomers (18% of total dose, compared to 8% and 9% with 1,2-DNB and 1,4-DNB, respectively). The major urinary metabolites of 1,2-DNB were S-(2-nitrophenyl)-N-acetylcysteine (42% of the dose), 2-nitroaniline-N-glucuronide (4%), 4-amino-3-nitrophenylsulfate (17%), 2-amino-3-nitrophenylsulfate (1.5%), and 2-(N-hydroxylamino)nitrobenzene (1-2%). The major urinary metabolites of 1,3-DNB were 3-aminoacetanilide (22%), 4 acetamidophenylsulfate (6%), 1,3-diacetamidobenzene (7%), and 3-nitroaniline-N glucuronide (4%). The major metabolites of 1,4-DNB were 2-amino-5 nitrophenylsulfate (35%), S-(4-nitrophenyl)-N-acetylcysteine (13%), and 1,4 diacetamidobenzene (7%). These results suggest that the DNB isomers are primarily metabolized by nitro group reduction and conjugation with glutathione. The testicular toxicant 1,3-DNB was apparently metabolized exclusively by reduction. PMID- 2893709 TI - Cryopreservation of rat and dog hepatocytes for studies of xenobiotic metabolism and activation. AB - Isolated human hepatocytes offer a unique way of studying the metabolism and mechanisms of action of drugs and toxic chemicals. Because of the irregular availability of human liver, a way of storing the hepatocytes until they can be conveniently used is required. Using rat and dog isolated hepatocytes, we have developed a procedure for cryopreserving hepatocytes in large numbers such as are needed for metabolism and toxicity studies. Hepatocytes were frozen in medium containing 10% dimethyl sulfoxide using a microcomputer-controlled freezing gradient and stored at -196 degrees C. Upon thawing, the total cell recovery for rat hepatocytes was 67%. Cell viability measured by trypan blue (TB) exclusion was 67%, 7-ethoxycoumarin (7-EOC) dealkylation 33%, and cytochrome P-450 75%, compared to fresh hepatocytes. With cryopreserved dog hepatocytes, the total cell recovery was 75%. TB exclusion was 62%, 7-EOC dealkylation 37%, and cytochrome P 450 68%, compared to fresh hepatocytes. The viability of cryopreserved hepatocyte preparations could be improved by density separation on Percoll giving a TB exclusion for rat hepatocytes of 85%, and 7-EOC dealkylation of 69% compared to fresh hepatocytes, with 67% of the viable cells recovered. Biphenyl was used as a substrate to measure integrated xenobiotic metabolizing activity by the hepatocytes. Total hydroxybiphenyl (OHB) formation, a mixed function oxygenase activity, was maintained in cryopreserved Percoll-treated rat hepatocytes at 86%, OHB glucuronide formation at 85%, and OHB sulfate formation at 20% of the values in fresh hepatocytes. In cryopreserved dog hepatocyte, total OHB formation was 39%, and OHB glucuronide and sulfate formation less than 10% of the values in fresh hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893710 TI - Oxidative metabolism of butylated hydroxytoluene by hepatic and pulmonary microsomes from rats and mice. AB - Metabolism of the antioxidant butylated hydroxytoluene (BHT; 2,6-di-tert-butyl-4 methylphenol) has been studied with liver and lung microsomes from rats and mice. The structures of several previously reported metabolites were confirmed, the identities of four new metabolites were determined, pathways of oxidation were investigated, and quantitative data were obtained for several of the products. Two main metabolic processes occur, hydroxylation of alkyl substituents and oxidation of the aromatic pi electron system. The former leads to the 4 hydroxymethyl product (BHT-BzOH) and a primary alcohol resulting from hydroxylation of a t-butyl group (BHT-tBuOH). Additional metabolites were produced by oxidation of BHT-BzOH to the corresponding benzaldehyde and benzoic acid derivatives. Hydroxylation of BHT-tBuOH occurs at the benzylic methyl position, and the resulting diol is oxidized further to the hydroxybenzaldehyde derivative. Oxidation of the pi system leads to the quinol, 2,6-di-t-butyl-4 hydroxy-4-methyl-2,5-cyclohexadienone, the quinone, 2,6-di-t-butyl-4 benzoquinone, and the quinone methide, 2,6-di-t-butyl-4-methylene-2,5 cyclohexadienone. Derivatives of the quinol and quinone with a hydroxylated t butyl group were also formed. Quantitative data demonstrate that BHT-BzOH is the principal metabolite in rat liver and lung microsomes. On the other hand, mice produce large amounts of both BHT-BzOH and BHT-tBuOH in these tissues. The metabolite profile was similar in rat liver and lung. Mouse lung, however, produced more quinone relative to other metabolites than mouse liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893711 TI - Evidence for diazotization of 14C-sulfamethazine [4-amino-N-(4,6-dimethyl-2 pyrimidinyl)benzene[U-14C]sulfonamide] in swine. The effect of nitrite. AB - Dietary nitrite greatly enhanced the conversion of orally administered 14C sulfamethazine (4-amino-N-(4,6-dimethyl-2-pyrimidinyl)benzene[U-14C]sulfonamide; 14C-sulmet) to 14C-desaminosulfamethazine [N-(4,6-dimethyl-2 pyrimidinyl)benzene[U-14C]sulfonamide; 14C-DA-sulmet] in swine. The disposition of 14C orally administered to swine as 14C-sulfamethazinediazonium tetrafluoroborate (4-[N-(4,6-dimethyl-2-pyrimidinyl)sulfonamido] [U-14C]diazonium tetrafluoroborate) was very similar to the disposition of 14C given to swine as 14C-sulmet in combination with nitrite. These results and other information discussed in the text provide evidence that 14C-sulmet, in the presence of nitrite under the acid conditions in the gastrointestinal tract, was diazotized and that this diazonium intermediate was converted to 14C-DA-sulmet and other unidentified 14C-labeled products. PMID- 2893712 TI - Mechanism-based inactivation of the major beta-naphthoflavone-inducible isozyme of rat liver cytochrome P-450 by the chloramphenicol analog N-(2-p nitrophenethyl)dichloroacetamide. AB - The effectiveness, selectivity, and mechanism of the inactivation of the major beta-naphthoflavone-inducible isozyme of rat liver cytochrome P-450 (BNF-B) by the chloramphenicol analog N-(2-p-nitrophenethyl)dichloroacetamide (pNO2DCA) have been investigated. Intraperitoneal administration of pNO2DCA to beta naphthoflavone-treated rats at doses of 10 and 100 mg/kg resulted in 72 and 95% decreases, respectively, in the ethoxyresorufin deethylase activity of subsequently prepared liver microsomes. Similar decreases were observed in the warfarin R-6 and R-8 hydroxylase activities of the microsomes. At the lower dose of pNO2DCA, only those R-warfarin hydroxylase activities attributable to BNF-B were decreased, whereas, at the higher dose, inhibition of additional cytochromes P-450 was evident. In vitro, pNO2DCA was found to be a highly efficient inactivator of purified BNF-B in a reconstituted system. The maximal rate constant for inactivation and the apparent Km for the inhibitor were 0.52 min-1 and 2.7 microM, respectively. Inactivation of BNF-B by pNO2DCA appears to involve an impairment in electron transfer from NADPH-cytochrome P-450 reductase, as evidenced by a decrease in the NADPH- but not the iodosobenzene-supported metabolism of ethoxycoumarin by the modified enzyme. However, in the absence of substrate, there was no decrease in the NADPH oxidase activity or in the steady state level of ferrous carbonyl complex formed enzymatically. Likewise, the maximal level of isosafrole metabolite-P-450 complex formed by BNF-B was not decreased by modification with pNO2DCA, although the rate of complex formation was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893713 TI - Selective inactivation by chloramphenicol of the major phenobarbital-inducible isozyme of dog liver cytochrome P-450. AB - Chloramphenicol (CAP) is a potent and effective mechanism-based inactivator of the major phenobarbital (PB)-inducible isozyme of dog liver cytochrome P-450 (PBD 2) in vitro. In a reconstituted system containing PBD-2, CAP causes a time- and NADPH-dependent irreversible loss of 7-ethoxycoumarin deethylase activity, with no loss of spectrally detectable cytochrome P-450. Inactivation is enhanced by cytochrome b5, and, in the presence of cytochrome b5, the concentration of CAP at which the rate constant for inactivation is half-maximal (Kl) and the maximal rate constant for inactivation (Kinact) are 5 microM and 1.2 min-1, respectively. CAP binds covalently to PBD-2 with a stoichiometry of 1 nmol of [14C]CAP bound/nmol of cytochrome P-450 inactivated. In addition, CAP is a selective inactivator of PBD-2. In intact liver microsomes from PB-treated dogs, CAP irreversibly inhibits androstenedione 16 alpha and 16 beta, but not 6 beta hydroxylation. Covalent binding of [14C]CAP to dog liver microsomes in vitro is increased 5.5 times by PB induction. This increase correlates well with the increased levels of immunochemically determined PBD-2 (5.8-fold) and 16 alpha and 16 beta hydroxylation of androstenedione (5.7- and 5.8-fold) in microsomes from PB-treated compared to control animals. Anti-PBD-2 IgG specifically inhibits by greater than 80% the covalent binding of [14C]CAP to microsomes from control and PB-treated dogs. Finally, in liver microsomes from PB-treated and control dogs, CAP appears to bind covalently to a single protein with the same molecular weight as PBD-2 as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. PMID- 2893714 TI - Conversion of bromobenzene to 3-bromophenol. A route to 3- and 4-bromophenol through sulfur-series intermediates derived from the 3,4-oxide. AB - Premercapturic acids derived from bromobenzene 3,4-oxide were found to act as precursors of 3- and 4-bromophenol in the rat and guinea pig. The 4-S- and 3-S- positional isomers used in this study were rat urinary metabolites and were prepared in unlabeled, radioactive, and 2,4,6-d3-labeled forms. These are not guinea pig urinary metabolites; the guinea pig does not completely acetylate cysteine conjugates, and this effect leads to urinary products arising from deamination of the cysteine moiety rather than to urinary premercapturic acids. Conversion to phenols was found to be much greater in the guinea pig than in the rat. We interpret our results as indicating that cysteine adducts, rather than the N-acetylcysteine adducts which were administered, are required intermediates in this metabolic route to 3- and 4-bromophenol. This route to phenols may be the major mode of phenol formation for many aromatic compounds. Sulfur-series metabolic products from bromobenzene also include thiocatechols, and these metabolites may be responsible for the hepatotoxicity of bromobenzene in high dosage. PMID- 2893716 TI - Mechanism of metabolic cleavage of a furan ring. AB - We studied the mechanism of metabolic cleavage of a furan ring, using a new hypolipidemic agent, ethyl 2-(4-chlorophenyl)-5-(2-furyl)oxazole-4-acetate (TA 1801), as a model compound. A TA-1801 analogue labeled with deuterium at the 5 position of its furan ring was administered orally to rats. The analysis of urinary metabolites by GC/MS revealed that the deuterium of the furan was retained in the ring-opened metabolite (M3). Metabolic cleavage of furan has been generally considered to proceed by hydroxylation of the 5-position followed by tautomerism and hydrolysis of the resulting 5-hydroxyfuran derivative. However, if the cleavage proceeded by this pathway, the deuterium of the 5-position would be eliminated during hydroxylation. Therefore, we propose that the ring was cleaved directly to form an unsaturated aldehyde, considering the mechanism of oxidation by cytochrome P-450. Although this "intermediate" was not detected in the biological specimens, a synthetic unsaturated aldehyde was transformed to the actual urinary metabolites M2 and M3 (major ring-opened metabolites) in the isolated rat liver. PMID- 2893715 TI - Isolation and identification of major metabolites of tixocortol pivalate in human urine. AB - The metabolism of tixocortol pivalate (PIVALONE), an anti-inflammatory steroid without systemic glucocorticoid effects, has been investigated in man. The analysis was conducted using urine samples collected from two volunteers who had received a 2-g oral dose of 14C-tixocortol pivalate as an oral suspension. Metabolites were purified and isolated from urine by normal phase HPLC, and structural identification was achieved by desorption chemical ionization/NH3 and electron impact/direct line introduction mass spectrometry. Unchanged tixocortol pivalate was not detected in urine; all metabolites were sulfo- and glucurono conjugates. Metabolites were identified in the neutral steroid fraction obtained after hydrolysis of conjugates. Metabolic transformations in common with cortisol were reduction of the 3-keto, delta 4 system, reduction of the C-20 carbonyl group, oxidation of the C-11 alcohol, and cleavage of the side chain at C-17. Specific metabolic pathways involving the C-21 thiol ester function were transformations into methylthio, methylsulfinyl and methylsulfonyl derivatives, and a reductive cleavage of the C-21-S bond leading to 21-methyl structures. Since none of these metabolites had binding affinity for glucocorticoid receptors in vitro, fast and extensive transformation of tixocortol pivalate into inactive metabolites provides an explanation for the large dissociation between the topical and systemic activities of this drug. PMID- 2893717 TI - Phenolic metabolites of amitriptyline and nortriptyline in rat bile. AB - Anesthetized bile fistula rats received amitriptyline (AT), its N-oxide (AT-NO), or nortriptyline (NT) at doses of 72 mumol/kg ip, and bile was collected for 6-9 hr. Isolation of metabolites was achieved by enzymic deconjugation and repeated TLC of extracted aglycones. Purified compounds were characterized by UV, NMR, and mass spectrometry, by color reactions, and by chemical interconversions. Besides the alcohols E-10-hydroxy-AT and 10,11-dihydroxy-AT, the phenol E-2-hydroxy-AT occurred as a major AT metabolite, while 2,10- and 2,11-dihydroxy-AT, 2,10,11 trihydroxy-AT, and 2-hydroxy-3-methoxy (or 3-hydroxy-2-methoxy)-AT were present in smaller quantities. Further minor metabolites were 2-hydroxy-11-oxo-AT, 3 hydroxy-AT, 3,11-dihydroxy-AT, and its dehydration product 3-hydroxy-10,11 dehydro-AT. The exact position of the functional groups was elucidated by the nuclear Overhauser effect (NOE) in NMR spectroscopy and by analyzing metabolite patterns in the bile of rats given E- or Z-10-hydroxy-AT. Administration of AT-NO led to a larger proportion of methylated catechols and a smaller one of 10 hydroxy metabolites. Besides the tertiary amines, rats given AT or AT-NO excreted the demethylated analogues of some of the hydroxylation products. The latter also occurred as metabolites of NT, the ratio of aromatic and aliphatic hydroxylation being lower than with AT or AT-NO. Urine of rabbits treated orally with AT contained mono- and dihydroxylated metabolites resulting from attack at positions 2, 3, 10, and/or 11 and the same methylated catechols as rat bile. PMID- 2893718 TI - Amitriptyline metabolites in human urine. Identification of phenols, dihydrodiols, glycols, and ketones. AB - From the urine patients being treated with amitriptyline, drug metabolites were extracted by adsorption to polystyrene. Nonconjugated compounds and aglycones liberated by enzymic hydrolysis were purified separately by repeated TLC and characterized by physicochemical and chemical methods. Besides the known E- and Z 10-hydroxy derivatives of amitriptyline (AT), nortriptyline (NT), and their primary amine analogue, two isomeric 10,11-dihydroxy compounds could be identified in each series. Metabolites with an oxo function in position 10 occurred in minor quantities. The phenols 2-hydroxy-NT and 2,11-dihydroxy-NT, as well as the 1,2-dihydrodiol derived from NT, were regularly present, while the corresponding tertiary amines as well as 3-hydroxy-AT and -NT were detected occasionally in very small amounts. PMID- 2893719 TI - 19F nuclear magnetic resonance analysis of the carbamate reaction of alpha-fluoro beta-alanine (FBAL), the major catabolite of fluoropyrimidines. Application to FBAL carbamate determination in body fluids of patients treated with 5'-deoxy-5 fluorouridine. AB - alpha-Fluoro-beta-alanine (FBAL), the major catabolite of the antineoplastic fluoropyrimidines, is an amino acid which is in equilibrium with its carbamate derivative in weakly alkaline aqueous solutions containing carbonate. In both water and control biological fluids (urine, plasma) spiked with FBAL (and sodium bicarbonate, in some cases), 19F NMR was used: (i) to determine the pH range over which FBAL carbamate is present (pH greater than or equal to 7), the maximum concentration formed occurring around pH 9, (ii) to show that the amino group of FBAL interacts very slowly with a non-protein plasma component to form a compound X, unstable in acid medium. The presumed structure of X is RCONHCH2CHFCOOH, with R different from an alkyl group but still unidentified. The behavior of FBAL in urine and plasma of rats treated with FBAL or 5'-deoxy-5-fluorouridine (5' dFUrd), a prodrug of 5-fluorouracil, and from patients treated with 5'-dFUrd was investigated. FBAL carbamate was not present in acid medium and was therefore absent in acidic human urine. However, it was found in alkaline rat urine. FBAL carbamate was found in plasma along with the compound X. The 19F NMR spectra of FBAL and derivatives are complex since alpha-fluoro-beta-ureido-propionic acid, the precursor of FBAL in the catabolic pathway of antineoplastic fluoropyrimidines, produces a signal overlapping that of FBAL carbamate, and very close to that of compound X.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893720 TI - Excretion and biotransformation of alfentanil and sufentanil in rats and dogs. AB - The excretion and biotransformation of alfentanil (ALF) and sufentanil (SUF), two recent analogues of the synthetic opioid fentanyl, were studied after single iv administration of the tritium-labeled drugs in male rats and dogs. The drugs were almost completely metabolized in the two species, which resulted in a large number of metabolites. The excretion of the metabolites was rapid and exceeded 95% within 4 days, except for that of ALF metabolites in dogs (about 85%). For ALF, excretion of the radioactivity with the urine (73% in rats, about 76% in dogs) exceeded that with the feces. For SUF, excretion of the radioactivity with the urine amounted to 38 and 60% and that with the feces to 62 and 40%, in rats and dogs, respectively. Bile-cannulated rats excreted 68% with the bile within 24 hr after SUF dosing, and about 22% of this biliary radioactivity was subjected to enterohepatic circulation. After an ALF dose, the biliary excretion amounted to 24%, and the enterohepatic circulation was minimal. The main metabolic pathways of the two drugs were the oxidative N-dealkylation at the piperidine nitrogen and at the amide nitrogen, oxidative O-demethylation, aromatic hydroxylation, and the formation of ether glucuronides. N-[4-(Hydroxymethyl)-4-piperidinyl]-N phenylpropanamide (M6) was the main metabolite of both ALF and SUF in rats. In dogs, the glucuronide of N-(4-hydroxyphenyl)propanamide (M5) was the main metabolite of ALF. After SUF dosing in dogs, N-[4-(methoxymethyl)-4-piperidinyl] N-phenylpropanamide was more abundant than M5. PMID- 2893721 TI - Metabolism of (+)-trans-delta 8-tetrahydrocannabinol in the mouse in vitro and in vivo. AB - (+)-trans-delta 8-Tetrahydrocannabinol (THC) was synthesized by condensation of (1R)-cis-verbenol and olivetol, and its in vitro and in vivo hepatic metabolism was studied in male mice. Metabolites were isolated by solvent extraction, purified, in the case of the in vivo study, by chromatography on Sephadex LH-20, and identified by combined gas chromatography/mass spectrometry. Twenty-three metabolites were identified. These were similar to those from the (-)-isomer in that the major metabolic route was hydroxylation at C-11 followed, in vivo, by oxidation to the corresponding acid. Further hydroxylation of these compounds at C-7 and in the side chain led to a series of disubstituted metabolites. The major sites of side chain hydroxylation were 1'-, 3'-, and 4'-. Less 2'-hydroxylation was observed than with the (-)-isomer, but the major difference between the two isomers was the production of 1'-hydroxy metabolites only from the (+)-isomer. Much less hydroxylation occurred at C-7 than with the (-)-isomer so that the 7,11 disubstituted compounds, which were major metabolites of (-)-trans-delta 8-THC, were formed in insignificant concentrations. Another difference between the metabolism of the two isomers, in vitro, was the presence of substantial concentrations of monohydroxy metabolites containing hydroxylation in the side chain; these compounds are absent in metabolic profiles from (-)-trans-delta 8 THC. An epoxide and its derived glycol were detected in vitro. Another major in vitro metabolic route was the formation of an acetate derivative of 11-hydroxy (+)-trans-delta 8-THC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893722 TI - Identification of the etodolac metabolite, 4-ureidoetodolac, in mouse, rat, dog, and man. PMID- 2893723 TI - [3H]chloramphenicol metabolism in human volunteer: oxamic acid as a new major metabolite. PMID- 2893724 TI - [The beta 2-pseudoselectivity of ISA (intrinsic sympathomimetic action)- consequences for differential therapy with beta-blockers with and without ISA?]. PMID- 2893725 TI - [Regulatory subpopulations of T-lymphocytes and blocking factors in the serum of patients with inoperable lung cancer treated with indomethacin]. AB - A considerable disturbance in the ratio of the immunoregulatory T-lymphocyte subpopulations detected by receptors to Fc-fragment of IgM, IgG and by theophilline was revealed in 70 patients with inoperable lung cancer as well as a considerable increase in the blocking circulating immunocomplexes (CIC) in blood serum of these patients. A single dose of indometacin (100 mg/kg) led to the reduction of immunoregulatory disbalance 3 hours after injection and to a decrease in the blocking CIC in blood serum. These data permit recommending the use of indometacin in the treatment of inoperable lung cancer patients. PMID- 2893726 TI - Approach to rhinitis. AB - Rhinitis is a common affliction of humans that can cause significant morbidity. Distinction between allergic and nonallergic varieties has important prognostic and therapeutic implications. Newer, nonsedating antihistamines and intranasal steroid preparations have greatly enhanced the treatment of these disorders. Distinguishing factors of viral and bacterial rhinitis have been reviewed. Early recognition of nasal cellulitis and mucormycosis with aggressive therapy is necessary to prevent serious complications. Multiple processes, including structural and drug-induced reactions, can mimic rhinitis. An orderly approach, including a good history and physical examination, coupled with use of the nasal smear, will allow the emergency physician to master this frequent complaint. PMID- 2893727 TI - Induction of c-fos, calcitonin gene expression, and acidic fibroblast growth factor production in a multipeptide-secreting neuroendocrine cell line. AB - The multipeptide-secreting 44-2C cell line maintains differentiated function when grown in a serum-free, growth factor- and hormone-deprived milieu. The cells continue to synthesize and secrete calcitonin (CT), CT gene-related peptide, neurotensin, and somatostatin and respond to cellular secretagogues such as GRF and acidic and basic fibroblast growth factor. We designed experiments to ascertain the functional role(s) of cellular factors involved in the maintenance of the differentiated state in 44-2C cells. We report here the phenotypic transformation that occurs in these cells in the course of adjustment to the serum-free state. We also show the differential increase in CT-specific mRNA, the transient induction of c-fos, and the characterization of biologically active acidic fibroblast growth factor. PMID- 2893728 TI - Growth hormone-releasing factor and fibroblast growth factor regulate somatostatin gene expression. AB - A multiple peptide-synthesizing clonal rat cell line was used to study the effect(s) of GRF and basic fibroblast growth factor (bFGF) on the synthesis and secretion of somatostatin (SS). The presence of SS-specific mRNA in 44-2C cells was shown morphologically by in situ hybridization. The release and cellular content of SS increased significantly after treatment with rat hypothalamic GRF (rGRF), the ED50 for rGRF stimulation of intracellular SS was 1.9 X 10(-11) M. GRF stimulated SS production in serum-supplemented and serum-free cultures. Results obtained after incubation of 44-2C cells with 125I-labeled rGRF indicated uptake and nuclear localization of rGRF by 44-2C cells. FGF stimulated the secretion and cellular content of SS. We propose that bFGF regulates the short term secretion and accumulation of SS and mediates rGRF-stimulated SS expression. PMID- 2893729 TI - Distribution of somatostatin receptors in RINm5F insulinoma cells. AB - Previous studies with heterogeneous populations of pancreatic cells have provided evidence for the presence of somatostatin (SRIF) receptors in cytosol and secretion vesicles, as well as the plasma membrane. To examine the distribution of SRIF receptors between soluble and membrane fractions in a homogeneous pancreatic islet cell population, we have used the clonal RINm5F insulinoma cell line. These cells contain specific, high affinity binding sites for [125I Try11]SRIF on the cell surface, and occupancy of these sites by SRIF and SRIF analogs correlates with inhibition of insulin secretion. Stable, steady state binding was achieved using both intact cells and membranes by performing binding incubations with [25I-Tyr11]SRIF at 22 C. Half-maximal inhibition of [125I Tyr11]SRIF binding occurred with 0.21 +/- 0.11 nM SRIF in membranes and 0.35 +/- 0.30 nM SRIF in cells. In contrast, the binding of [125I-Tyr11]SRIF to cytosolic macromolecules was not reduced by concentrations of SRIF as high as 100 nM, demonstrating that this binding was of much lower affinity. RINm5F membranes were further purified using a Percoll gradient to prepare a microsomal fraction, which was enriched in adenylate cyclase activity, and a secretory granule fraction, which was enriched in insulin. [125I-Tyr11]SRIF binding to the microsomal fraction (3.8 +/- 0.3 fmol/mg) was 3 times higher than to secretion granules (1.2 +/- 0.2 fmol/mg). Thus, high affinity SRIF binding sites were most abundant in microsomal membranes and were low or undetectable in secretory granules and cytosol. To determine whether translocation of SRIF receptors to the plasma membrane accompanied insulin secretion, we examined the effects of various insulin secretagogues on [125I-Tyr11]SRIF binding to intact cells. Leucine (20 mM), glyceraldehyde (15 mM), forskolin (1 microM), and glucagon (1 microM) stimulated insulin release 1.5- to 4.0-fold in different experiments. However, these secretagogues did not increase [125I-Tyr11]SRIF binding. In summary, our results indicate that high affinity SRIF receptors in RINm5F cells are located primarily on the plasma membrane and that the concentration of SRIF receptors at the cell surface is independent of the secretory activity of the cells. PMID- 2893730 TI - Pathophysiological role of thyroid blocking antibody in patients with primary hypothyroidism. AB - The pathophysiological role of thyroid blocking antibody (TBAb) in patients with adult primary hypothyroidism and the mechanism of TBAb action were studied. A sensitive bioassay for TBAb, which inhibits the TSH-induced cAMP accumulation, was established using normal human thyroid cells in culture. Thirty-four patients with primary hypothyroidism consisting of 17 goitrous and 17 non-goitrous patients were examined. Two out of 17 goitrous patients (11.8%) and three out of 17 non-goitrous patients (17.6%) were TBAb positive. There were no significant differences between TBAb positive and negative patients in terms of the severity of hypothyroidism or the titers of MCHA or TGHA. Four out of the five TBAb positive IgGs had strongly positive thyrotropin binding inhibitor immunoglobulin activities. All five TBAb-positive IgGs inhibited the cAMP increase induced by Graves' IgG, but did not affect the action of either prostaglandin E1 or cholera toxin. However, three TBAb positive IgG also inhibited the cAMP increase induced by forskolin. These findings indicate: 1) TBAb is present in hypothyroid patients with autoimmune thyroiditis and TBAb may play a role in the pathophysiology of these patients. 2) TBAb may inhibit the action of TSH not only at the level of the TSH receptor, but also at a different site from the TSH receptor. PMID- 2893731 TI - [Effect of testosterone on the dihydro-orotase activity of the rat liver and kidney]. PMID- 2893732 TI - Giant bile duct stones--non-surgical treatment. PMID- 2893733 TI - Successful treatment of recurrent cerebral empyema and brain abscesses with imipenem. AB - Imipenem was successfully used to treat a case of subdural empyema complicated by multiple cerebral abscesses, in which surgery and therapy with other antibiotics had previously failed. Imipenem concentrations in serum, cerebrospinal fluid and the cerebral abscess were much higher than the MICs for the infecting organisms, qualifying this antibiotic as an effective option in therapy of suppurative intracranial infections. PMID- 2893734 TI - Angina pectoris in a case of Takayasu's disease: revascularization by coronary ostioplasty and bypass grafting. AB - A young man with Takayasu's disease had severe right and left coronary ostial stenoses. Severe angina was relieved by operation at which the right coronary ostium was enlarged by a pericardial patch extending across the stenosis from aorta to coronary artery; the aortic end of a vein graft to the left coronary artery was attached to this patch. This technique may reduce the risk of recurrence of ostial stenosis or of stenosis at graft origins. PMID- 2893735 TI - Sulfadimethoxine-bucolome interaction in rabbits: role of N4 acetylsulfadimethoxine, a major metabolite of sulfadimethoxine. AB - The role of N4-acetylsulfadimethoxine (N4-AcSDM), a major metabolite of sulfadimethoxine (SDM), in protein binding and pharmacokinetic interactions between SDM and bucolome (BCP) was investigated in rabbits. When SDM and BCP were intravenously co-administered, BCP indirectly reduced the serum protein binding of SDM by causing a marked increase of N4-AcSDM concentration in serum, and significantly increased the steady-state volume of distribution (Vss) and total body clearance (C1tot) of SDM. In addition, the co-administration of N4-AcSDM was found to increase Vss and C1tot of SDM. These results lead us to conclude that N4 AcSDM plays an important role in protein binding and pharmacokinetic interactions between SDM and BCP in rabbits. Several investigations have demonstrated that a metabolite plays an important role in drug-drug interaction. For example, Sellers et al. (1) reported that when warfarin and chloral hydrate are co-administered, a major metabolite of chloral hydrate, trichloroacetic acid, reduces the plasma protein binding of warfarin and enhances its anti-coagulant activity. Our previous paper (2) showed that probenecid indirectly reduces the plasma protein binding of sulfadimethoxine (SDM) by causing a marked increase in the plasma concentration of N4-acetylsulfadimethoxine (N4-AcSDM), which is a major metabolite of SDM (3) and strongly displaces SDM from its plasma protein binding sites (2). However, as yet the role of this metabolite in drug-drug interaction has not been fully examined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893736 TI - Pharmacokinetics of diazepam and four 3-hydroxy-benzodiazepines in the cat. AB - Biotransformation and elimination of diazepam and four 3-hydroxy-benzodiazepines after i.v. injection in anaesthetized cats were investigated. Decay of plasma concentration of 3-hydroxy-benzodiazepines was slow and plasma concentrations of their glucuronides were lower than of unchanged parent compounds. In the urine, very low excretion rates of all investigated benzodiazepines were found during the first eight hours. It is concluded that cats poorly glucuronidate 3-dydroxy benzodiazepines. PMID- 2893737 TI - Contribution of beta-adrenoceptors to the dopamine-induced elevation of cyclic 3',5'-adenosine monophosphate levels in mouse lymphocytes. AB - The receptors involved in the cyclic adenosine 3',5'-monophosphate (cAMP) increasing action of dopamine (DA) in mouse lymphoid cells were determined by comparing the potencies of specific DA receptor and adrenoceptor antagonists to inhibit the cAMP response to DA and to isoproterenol. The beta-adrenoceptor antagonists propranolol, pindolol and dichloroisoproterenol were the most potent inhibitors of the response to both DA and isoproterenol. Their potencies were 2-3 orders greater for the inhibition of DA than isoproterenol action. SCH 23390 (selective DA1 antagonist) and haloperidol (mixed DA1/DA2 antagonist) inhibited the DA action only at high concentrations (10(-5)-10(-4) M) which did not affect the response to isoproterenol. These results indicate that beta-adrenoceptors are involved in the DA-induced elevation of mouse lymphocyte cAMP. PMID- 2893738 TI - Dopamine D-2 receptors in canine brain: ionic effects on [3H]neuroleptic binding. AB - In order to determine the effects of monovalent cations on the binding of 3H neuroleptics to canine striatal dopamine D-2 receptors, a study of the effects of ions on the binding of two 3H-neuroleptics from different drug classes was undertaken. Dopamine D-2 receptors are selectively labeled in a sodium-sensitive manner by the benzamide ligand [3H]YM-09151-2. In the presence of 120 mM NaCl, [3H]YM-09151-2 had a dissociation constant of 55 pM and a maximal receptor density of 34 pmol/g of tissue. In the absence of NaCl, the dissociation constant was 440 pM with no change in the receptor density. The binding of [3H]YM-09151-2 (52 pM) was increased by 700% with 150 mM Na+, 440% with 500 mM Li+ and 290% with 500 mM K+. The ion concentrations producing half-maximal increases in binding were 4 mM Na+, 8.5 mM Li+ and 115 mM K+. The ionic strength control, N-methyl-D glucamine, did not increase [3H]YM-09151-2 binding. [3H]Spiperone binding was much less affected by monovalent cations. Analysis of saturable binding showed that these changes were due to changes in binding affinity, independent of changes in receptor density. The sulfhydryl alkylating agent, N-ethylmaleimide, inactivated [3H]YM-09151-2 binding. Sodium ions at 120 mM protected approximately 40% of the susceptible sites while lithium and potassium ions (120 mM) did not. The anion exchange blocker, 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid (DIDS), has been shown to be capable of blocking the effect of Na+ on the binding of agonists to alpha 2-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893739 TI - Methamphetamine-induced changes in the striatal-nigral dynorphin system: role of D-1 and D-2 receptors. PMID- 2893740 TI - Basic fibroblast growth factor: expression in cultured cells derived from corneal endothelium and lens epithelium. AB - We have examined the possible expression of fibroblast growth factor in cultured cells derived from bovine lens epithelium and corneal endothelium. Lens epithelial, but not corneal endothelial, cells were found to express the acidic fibroblast growth factor (aFGF) gene, whereas both cell types express the gene encoding basic fibroblast growth factor (bFGF), a related mitogen. Expression of bFGF was further examined. Both corneal endothelial and lens epithelial contain 3.7 and 7.0 k bFGF gene transcript, which are translated into material closely related, if not identical with bFGF. Essentially all of the bFGF-like material is bioactive, i.e. it can stimulate the proliferation of capillary endothelial or corneal endothelial cells and the stimulation is blocked by anti-bFGF antibodies. Our results indicate that bFGF derived from corneal endothelial and lens epithelial cells may act as a paracrine and autocrine growth factor in both cell types. Thus, bFGF present in both cell types may play an important role in the proliferation of injured or transformed ocular tissues. PMID- 2893741 TI - Opioid mechanisms involved in the slow potential change and neuronal refractoriness during cortical spreading depression. AB - The slow potential change (spc) accompanying spreading depression (SD) was studied in rats and in a seizure-sensitive strain of Mongolian gerbil under three different experimental paradigms, each involving the use of naloxone. Gerbils undergoing electroconvulsive shock treatment displayed SD during the post-ictal phase, which was blocked by the intraperitoneal (i.p.) administration of naloxone (20-50 mg kg-1). Topical application of naloxone to the exposed cortex of the anaesthetized gerbil and rat blocked the spc of SD evoked by KCl. Microiontophoretic ejection of naloxone during extracellular recordings reversed cell refractoriness following the spc, demonstrated by the observation of a maintained sensitivity to iontophoretic pulses of glutamate. The results suggest a possible involvement of naloxone-sensitive processes in the mechanism responsible for cortical SD. PMID- 2893743 TI - [Liquid chromatography in pharmaceutical analysis: determination in tablets of famotidine, a new H2-antagonists]. PMID- 2893742 TI - Evidence for reactive synaptogenesis in the ventrolateral thalamus and red nucleus of the rat: changes in high affinity glutamate uptake and numbers of corticofugal fiber terminals. AB - High affinity glutamate uptake into corticofugal fiber terminals was measured in the ventrolateral thalamus and red nucleus at varying time intervals after lesions were made by kainic acid in the contralateral interpositus nucleus of the cerebellum in rats. Under similar conditions the density of cortical fiber terminals was estimated using the Fink-Heimer impregnation technique. 1. Glutamate uptake steadily increased in the ventrolateral thalamus up to 60 days after lesions in the contralateral cerebellum. 2. Similar changes were noted in the red nucleus. 3. The changes were dependent on the integrity of corticofugal fibers to the thalamus and red nucleus. 4. No changes in uptake of gamma aminobutyric acid were noted. 5. Saturation curves for glutamate uptake suggested a change in the maximal number of transport sites. 6. Fink-Heimer degeneration studies showed an increase in cortical terminals in the ipsilateral ventrolateral thalamus and in both rostral and caudal regions of the red nucleus following lesions in the contralateral interpositus nucleus. The data are consistent with an increase in the number of cortical fiber terminals in reaction to loss of cerebellar input to the ventrolateral thalamus and red nucleus. This study correlates anatomical and biochemical evidence for collateral sprouting in a model based on electrophysiologic data in the red nucleus and extends the model to include the thalamus. PMID- 2893744 TI - [Biological activity of the sum of the valepotriates isolated from Valeriana alliariifolia]. AB - The native sum of valepotriates isolated from Val. alliariifolia Adams which was named valiracyl is an agent of low toxicity and exerts a pronounced neurotropic effect. Valiracyl suppresses the orientation reflex of animals in an "open field", decreases a spontaneous and caffeine-stimulated motor activity, potentiates and prolongs the action of barbiturates, significantly reduces aggressiveness of animals, decreases sensitivity to the convulsant effects of corasol and thiosemicarbazide, produces the antihypoxic and mild myorelaxant actions. The neurotropic effects of valiracyl are related to increased level of the GABA inhibition mediator and decreased intensity of bioenergetic processes in the brain. PMID- 2893746 TI - Alkyl-linked diquinolines are monofunctional AT-selective DNA-intercalating agents. AB - The binding of a homologous series of alkyl-linked 4-aminodiquinolines to circular and linear DNAs was studied using viscometric titrations and equilibrium dialysis. The compounds are monofunctional intercalators with the capacity for intercalative binding reaching a peak for the heptane homologue. They show marked AT-base pair selectivity, which suggests that the non-intercalated quinoline ring may lie in the DNA minor groove. Affinities for calf thymus DNA increase as the alkyl chain is lengthened, falling in the range 6 to greater than 250 X 10(4) M-1 in a buffer of I 0.01. The association constant of the heptane diquinoline decreases with increasing ionic strength, 2.1 cations being released per bound dipositive ligand molecule. All the agents are growth inhibitory towards mouse leukemia cells in culture with IC50 values in the range 0.06-18 microM. PMID- 2893745 TI - Biosynthesis of intestinal microvillar proteins. Effect of castanospermine on cell-free synthesis of aminopeptidase N. AB - Pig small intestinal mRNA was translated in a rabbit reticulocyte lysate system supplemented with microsomal membranes. Castanospermine, an inhibitor of glucosidase I, induced a high mannose-glycosylated form of microvillar aminopeptidase N (EC 3.4.11.2) of increased molecular mass, indicating the blocked removal of glucose residues. In contrast to its reduced expression in a mucosal explant system [(1986) Biochem. J. 240, 777-782], this molecular form of aminopeptidase N was at least as abundant in cell-free translation as its normal high mannose-glycosylated counterpart, ruling out degradation taking place in the rough endoplasmic reticulum. Degradation of newly produced, malprocessed enzyme must therefore occur at a later stage during intracellular transport, presumably in the sarcoplasmic reticulum or in transitional elements between this organelle and the Golgi complex. PMID- 2893747 TI - Functional multiplicity of atrial natriuretic peptide receptors on cultured rat Leydig tumor cells. AB - Native rat atrial natriuretic peptide (NANP) was shown to bind with high affinity and to increase intracellular levels of cGMP in cultured rat Leydig tumor cells. A linear analog of NANP which lacks the disulfide-linked bridge structure also bound with high affinity but did not increase levels of intracellular cGMP or antagonize the increase of this cyclic nucleotide by NANP. These data are consistent with the existence of two functional subpopulations of ANP receptors on cultured rat Leydig tumor cells; one which is capable of activating guanylate cyclase and one which is not linked to this enzyme. PMID- 2893749 TI - [Atheistic work of feldshers and midwives among women]. PMID- 2893748 TI - Tick-borne encephalitis and haemorrhagic fever with renal syndrome in Europe. Report on a WHO meeting. PMID- 2893750 TI - [Performing general dispensary care of the female population in the initial stage of medical service]. PMID- 2893751 TI - [The development of research on the neurohumoral regulation of organic functions of the visceral system 1917-1987]. PMID- 2893752 TI - Effect of indomethacin on the proliferative and differentiation activity in the haemopoietic system of lethally irradiated mice after syngeneic bone marrow transplantation. AB - The effects of indomethacin treatment on the proliferation and differentiation of haemopoietic stem cells of bone marrow grafts in lethally irradiated mice were investigated. Indomethacin was given subcutaneously, on days 3 to 5 after irradiation, in 6 doses of 0.05 mg per mouse. On day 6 after irradiation, an increased self-renewal of the settled colony-forming cells and an increased amount of differentiated cells were observed in the spleens of the mice treated. Simultaneously, a decreased maturation of the erythroid cells was demonstrated. The effects observed may be explained by the indomethacin-induced inhibition of prostaglandin biosynthesis. PMID- 2893753 TI - Characteristics of superficial layer neurons in the mouse cingulate cortex. An electrophysiological in vitro study. PMID- 2893754 TI - [Studies on the immunoregulation of anti-thyroglobulin antibody synthesis by lymphocytes in the patients with Hashimoto's disease and Graves' disease]. AB - Anti-thyroglobulin antibody (aTg) synthesis by the lymphocytes in the peripheral blood and the thyroid gland were studied in patients with Hashimoto's disease (HD) or Graves' disease (GD), all in euthyroid states, to clarify the mechanism of autoantibody synthesis. The ability of the lymphocytes to synthesize aTg was analyzed in the culture system of lymphocytes incubated in a concentration of 1 X 10(6) cells/ml for 7 days at 37 degrees C in 5% CO2-95% air. The B cells alone were also cultured in the absence of T cells or PWM to estimate their abilities on spontaneous aTg synthesis. The regulatory functions of T cells on aTg synthesis by B cells were investigated in cross-combination cultures of B cells and an equal number of T cells. The concentration of aTg and total IgG in cultured medium were measured by sensitive enzyme immunoassay developed by us, and the capacity on aTg synthesis was expressed as aTg/IgG ratio (aTg%). The surface markers of lymphocytes in the peripheral blood and the thyroid gland were determined by flowcytometry using mouse monoclonal antibodies (CD3, CD4, CD8, OKIa1, CD20 and Leu7). These results were obtained as follows: 1) All the lymphocytes from the peripheral blood, thyroid gland and bone marrow of HD patients synthesized much more aTg (3.1 +/- 1.6, 2.2 +/- 0.9, 1.5 +/- 0.5%, respectively) than those from normal peripheral blood lymphocytes (1.0 +/- 0.9%). This hyper-function of aTg synthesis by the lymphocytes in HD patients was caused by the presence of activated B cells and the predominance of helper T cells. 2) Both the lymphocytes from the peripheral blood and the thyroid gland in GD patients synthesized the same level of aTg (0.7 +/- 0.7%) as in normal subjects. However, the lymphocytes from bone marrow and lymph nodes, which were indicated by Benner et al. to play a main role in antibody synthesis after immunization with antigen, were involved in aTg synthesis (1.8 +/- 1.2, 5.4 +/- 1.1%, respectively). 3) There was no correlation between aTg synthesis and CD4+/CD8+ ratio of the peripheral blood lymphocytes in AITD patients. These results suggest that aTg synthesis in HD patients is an expression of abnormal immune reaction due to the presence of aTg specific activated B cells and dysfunction of regulatory T cells, and that aTg production by the lymphocytes from the bone marrow and lymph nodes in GD patients is resulted from a normal immune response to the high level of thyroglobulin in the blood.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2893755 TI - Alpha 2-adrenergic receptors in brown adipose tissue of infant rats--I. Identification and characteristics of binding sites in isolated plasma membranes. AB - 1. Alpha 2-Adrenoceptor antagonists [3H]yohimbine and [3H]RX 781094 and the partial alpha 2-agonist [3H]clonidine exhibited specific binding to plasma membrane fragments isolated from interscapular brown fat of 7-day-old rats. 2. Competition studies with epinephrine, yohimbine and practolol revealed that [3H]norepinephrine, the principal in vivo agonist acting upon brown adipocytes, can readily bind to alpha 2-adrenoceptors in brown fat of infant rats. 3. The presence of alpha 2-adrenoceptor subclass in brown fat of infant rats may play a role in the sympathetic regulation of this rapidly proliferating tissue. PMID- 2893756 TI - Evidence for neurotransmitter plasticity in vivo. II. Immunocytochemical studies of rat sweat gland innervation during development. AB - Previous studies of the cholinergic sympathetic innervation of rat sweat glands provide evidence for a change in neurotransmitter phenotype from noradrenergic to cholinergic during development. To define further the developmental history of cholinergic sympathetic neurons, we have used immunocytochemical techniques to examine developing and mature sweat gland innervation for the presence of the catecholamine synthetic enzymes tyrosine hydroxylase (TH) and dopamine beta hydroxylase (DBH) and for two neuropeptides present in the mature cholinergic innervation, vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP). In 7-day old animals, intensely TH- and DBH-immunoreactive axons were closely associated with the forming glands. The intensity of both the TH and DBH immunofluorescence decreased as the glands and their innervation developed. Neither TH-IR nor DBH-IR disappeared entirely; faint immunoreactivity for both enzymes was reproducibly detected in mature animals. In contrast to noradrenergic properties, the expression of peptide immunoreactivities appeared relatively late. No VIP-IR or CGRP-IR was detectable in the sweat gland innervation at 4 or 7 days. In some glands VIP-IR first appeared in axons at 10 days, and was evident in all glands by 14 days. CGRP-IR was detectable only after 14 days. In addition to VIP-IR and CGRP-IR, we examined the sweat gland innervation for several neuropeptides which have been described in noradrenergic sympathetic neurons including neuropeptide Y, somatostatin, substance P, and leu- and met-enkephalin; these peptides were not evident in either developing or mature sweat gland axons. Our observations provide further evidence for the early expression and subsequent modulation of noradrenergic properties in a population of cholinergic sympathetic neurons in vivo. In addition, the asynchronous appearance during development of the two neuropeptide immunoreactivities raises the possibility that the expression of peptide phenotypes may be controlled independently. PMID- 2893757 TI - Porcine D-amino acid oxidase: determination of the mRNA nucleotide sequence by the characterization of genomic and cDNA clones. AB - Oligodeoxynucleotide probes derived from the published amino acid (aa) sequence for D-amino acid oxidase (DAO) [Ronchi et al. J. Biol. Chem. 259 (1982) 8824 8834] were used to screen cDNA libraries made from porcine kidney cortex and liver. Whereas no clones were obtained from kidney mRNAs, 20 independent ones were isolated from the liver library. Surprisingly, all of them carried only partial cDNAs for DAO starting around aa 100 in the coding sequence and extending for up to 250 bp in the 3'-noncoding sequence. One of these clones, pULB9103, was used to screen a porcine genomic library and allowed the isolation of DAO gene clone phULB001. Four exons encoding aa 1-151 were identified and sequenced, as well as the relevant exon-intron junctions. The mRNA sequence coding for DAO has been reconstituted from the genomic and cDNA sequences; its analysis by computer did not reveal any significant secondary structure, or particular feature, which could explain the failure to obtain full-length cDNAs. PMID- 2893759 TI - [Hygienic evaluation of the curriculum in secondary rural schools]. PMID- 2893758 TI - Molecular analysis of mouse alcohol dehydrogenase: nucleotide sequence of the Adh 1 gene and genetic mapping of a related nucleotide sequence to chromosome 3. AB - The mouse has three genes (Adh) encoding alcohol dehydrogenase (ADH) enzymes of different tissue specificity and catalytic properties. Identified regulatory loci are known to affect the expression of Adh-1 and Adh-3, which are closely linked on chromosome 3. The Adh-1 gene product is expressed predominantly in liver, and its mRNA product is androgen-inducible in kidney. In this study, genomic clones of Adh-1 were obtained from a Balb/cJ DNA library. The nucleotide sequences of all exons, intron/exon boundaries and 5'- and 3'-flanking regions were obtained. The gene spans nearly 13 kb and is divided into nine exons and eight introns. The transcription start point of this gene was determined by S1 nuclease mapping studies and presumptive regulatory regions in the 5'-flanking regions were identified, including a TATA box and a glucocorticoid-responsive element. A restriction fragment length polymorphism in the Adh-1 gene was identified among inbred strains and mapped at the [Adh-1, Adh-3] complex on chromosome 3. An additional 'Adh-like' sequence in the genome was also mapped to chromosome 3 approx. 9 centiMorgans from Adh-1. PMID- 2893760 TI - Hydrophobic adhesin of E coli in ulcerative colitis. AB - Pathogenic E coli have adhesive properties which are mirrored by an increase in their surface hydrophobicity. E coli isolated from patients with ulcerative colitis possess a mannose resistant adhesin similar to that found in pathogenic E coli. In this study 42 E coli isolates from patients with colitis have been compared with 15 from controls to assess hydrophobicity and cellular adherence. The salting out method and the buccal epithelial cell technique were used respectively. E coli isolated from colitics are significantly more hydrophobic than control E coli (p less than 0.001). The salting out score correlates negatively with the buccal epithelial cell adhesion index. When E coli are grown at 18 degrees C both properties are temporarily reduced suggesting that they are related to each other. The salting out method clearly differentiates between E coli isolated from colitics and controls, and offers a simple method of detecting adhesive E coli in inflammatory bowel disease. PMID- 2893761 TI - Double blind comparison of the effects of cimetidine, ranitidine, famotidine, and placebo on intragastric acidity in 30 normal volunteers. AB - Continuous measurement of 24 hour intragastric acidity was carried out in 30 normal volunteers during treatment with placebo, cimetidine 800 mg, ranitidine 300 mg, and famotidine 40 mg in a double blind study. Medication was taken after the evening meal (post cenam nocte, PCN). Median 24 hour acidity decreased with all H2-receptor antagonists from 25.1 mmol/l on placebo to 10 mmol/l (-60.1%) during cimetidine, to 3.2 mmol/l (-87.25%) during ranitidine and to 2.5 mmol/l ( 90.0%) during famotidine treatment (p less than 0.0005). All drugs significantly inhibited night time acidity but only famotidine decreased acidity during the late morning compared with placebo. Significantly greater acid reduction was seen with famotidine and ranitidine compared with cimetidine but no difference was found between famotidine and ranitidine. PMID- 2893762 TI - Antibodies against enterotoxigenic Escherichia coli in the colostrum isolated from infants with diarrhea. AB - The role of certain types of Escherichia coli in infectious diarrhea in infants and young children is well known. Infants who are breast-fed are less prone to gastroenteritis during their first year of life. Antibodies against three types of fimbrial antigens (adhesions) of enterotoxigenic E. coli (ETEC) in the colostrum were studied. The hemagglutination inhibition test method was used to detect antibodies against ETEC adhesions, i.e. colonization factors, I and II and fimbria type I. The colostrum of mothers on the 1st and 3rd day post partum was standard for the presence of antibodies. The results show that most of the colostrum samples contained antibodies against adhesions of the types of ETEC that we worked with. This study will enhance the knowledge as to why mothers should breast-feed their babies. PMID- 2893763 TI - [Workshop seminar: Mononitrate. 28 November 1987, Frankfurt a. M. Prevention of ischemia in all coronary patients. 24-hour attack-free periods--a realistic goal]. PMID- 2893764 TI - Effect of modafinil on pancreatic exocrine secretion in rats. A comparison with adrafinil and related drugs. AB - The effects of modafinil and adrafinil, 2 drugs that induce locomotor hyperactivity, and those of the parent compounds CRL 40467 and CRL 40385, were studied on the external pancreatic secretion of anaesthetized and conscious rats. In anaesthetized rats modafinil, adrafinil, and CRL 40385 antagonized the central vagal stimulation of protein output induced by 2-deoxy-D-glucose in the pancreatic juice. In conscious rats, modafinil and adrafinil inhibited the output of protein in the basal interdigestive pancreatic secretion. Modafinil was more active than adrafinil as an inhibitor of pancreatic secretion. The effects of modafinil and adrafinil were different from those of sympathetic amines and dopamine: they did not stimulate the output of bicarbonate in anaesthetized rats, and pancreatic inhibition observed in conscious rats was not inhibited by either yohimbine or prazosin. PMID- 2893765 TI - [Quality of life in antihypertensive therapy]. AB - It is well known that distinct antihypertensive drugs have a different impact on compliance and on quality of life of patients. Therefore, we must ask under what conditions a refusal of antihypertensive medication can be justified and what its consequences are with regard to cardiovascular morbidity and mortality. An aspect of this latter question is answered by a prospective study on cardiovascular risks in a cohort of 416 middle-aged male blue-collar workers followed over three years: In the subgroup of 94 workers with mild or manifest hypertension few aspects of quality of life only were improved in the untreated (54%) as compared to the treated (46%) hypertensives. On the other hand, longterm cardiovascular risk was considerable: every third worker with untreated mild hypertension (140 to 160/90 to 100 mmHg; n = 30) exhibited signs of early left ventricular hypertrophy, as assessed by one- and two-dimensional echocardiography. The most impressive difference was found with regard to the diameter of left atrium (T = 3.02; p less than .01). The second part of the paper presents first results of a test-statistical evaluation: a German version of a well known measurement approach to quality of life in the United States is applied in 50 hypertensives and 56 normotensives. Internal consistency, stability and discriminant power of the questionnaire were very satisfying. Hypertensives compared to normotensives and treated hypertensives compared to untreated hypertensives showed significant differences on several subscales (esp. "general wellbeing", "vitality"). Results indicate that this measurement approach can be reliably used in further studies. PMID- 2893767 TI - Testicular vasculitis: implications for systemic disease. AB - Nine cases of testicular vasculitis were identified from the surgical pathology and autopsy files of the Johns Hopkins Hospital. In three cases this was the initial manifestation of polyarteritis nodosa. Two of these men presented with recurrent testicular pain and fever, with orchiectomy samples showing focal infarcts and necrotizing vasculitis. The third man presented with epididymitis, with his biopsy specimen showing vasculitis. In two cases, men presented with systemic and testicular signs of polyarteritis nodosa, and the diagnosis was made on testicular biopsy and later studied at autopsy. In another case, the testicular lesions were seen with Goodpasture's syndrome; the patient was thoroughly studied at autopsy, and no evidence of polyarteritis nodosa was found. In the remaining three cases, testicular vasculitis was identified incidentally without diseases associated with vasculitis, one at orchiectomy for prostate adenocarcinoma and the other two at autopsy. Polyarteritis nodosa is the most common cause of necrotizing vasculitis of the testes, and pathologists should recognize the rare testicular presentation of this disease. However, testicular vasculitis also may be seen with other systemic diseases associated with vasculitis. Three of our cases were seen without systemic vasculitis, suggesting that testicular vasculitis may occur as an isolated finding without being a manifestation of systemic disease. PMID- 2893768 TI - Characterisation and uses of a hypervariable DNA polymorphism associated with the human JH immunoglobulin gene locus. AB - A DNA hypervariable polymorphism associated with the human immunoglobulin JH gene locus on chromosome 14 is described. Its potential applications include the distinguishing of cells as host or donor in a transplantation situation as well as characterisation of immunoglobulin gene rearrangements. PMID- 2893766 TI - Growth hormone secretion during pregnancy: altered effects of growth hormone releasing factor and insulin-like growth factor-I in vitro. AB - Growth hormone (GH) secretion is controlled by growth hormone releasing factor (GRF) but changes in the circulating level of this hormone are difficult to measure. Insulin-like growth factor (IGF-I) is a GH-dependent growth factor which significantly but slightly inhibits stimulated GH release in vitro. We have tested the effects of GRF and IGF-I on GH release in pregnancy, a state in which serum concentrations of GH are elevated and levels of IGF-I are lowered. We have found, in a system of acutely dispersed adenohypophysial cells prepared from pregnant (day 21-23) or control cycling female rats, that adenohypophysial cells from pregnant rats have an increased GH release with GRF. In contrast, IGF-I inhibition is similar but slightly smaller. These altered responses may result in elevated serum GH levels during pregnancy. PMID- 2893769 TI - Adrenoceptor mediated plasma potassium fluxes in domestic fowl. PMID- 2893770 TI - [Hepatic encephalopathies]. AB - The functional disturbances of the central nervous system in hepatic encephalopathy are due to several coexisting pathogenetic factors: Endogenous neurotoxins, imbalance of amino acids in blood plasma and alterations of the blood-brain barrier. These factors, in turn, effect alterations of neurotransmitters and their receptors. Therapeutic interventions are aimed at the inhibition of ammonia production by protein restriction, lactulose or antibiotics. A new therapeutic concept is the application of branched chain amino acids. Their effect is based on the stimulation of protein synthesis in muscle, enhanced urea synthesis in the liver and increased ammonia detoxification by glutamine synthesis in the brain. PMID- 2893771 TI - Lectinophagocytosis: a molecular mechanism of recognition between cell surface sugars and lectins in the phagocytosis of bacteria. PMID- 2893772 TI - Efficacy against footrot of a Bacteroides nodosus 265 (serogroup H) pilus vaccine expressed in Pseudomonas aeruginosa. AB - Pili of Bacteroides nodosus 265 (serogroup H) were expressed in Pseudomonas aeruginosa both alone and in combination with pili from B. nodosus 198 (serogroup A). Pilin genes from B. nodosus were introduced on plasmid-borne, thermoregulated expression systems, either singly or as tandem genes from two separate strains in a single transcription unit. Despite the absence of a posttranslational cleavage of pilin which occurs in B. nodosus, pili prepared from P. aeruginosa harboring the pilin gene of B. nodosus 265 protected sheep against footrot after challenge by B. nodosus 265. Organisms harboring pilin genes from the two different serogroups of B. nodosus produced serologically distinct populations of pili on each cell, and pili from these cells protected sheep against footrot after challenges with B. nodosus strains 198 and 265. PMID- 2893773 TI - Distribution and degree of heterogeneity of the afimbrial-adhesin-encoding operon (afa) among uropathogenic Escherichia coli isolates. AB - The afimbrial adhesin (AFA-I) from a pyelonephritic Escherichia coli isolate (KS52) is a mannose-resistant, P-independent, X-binding adhesin, expressed by the afa-1 operon. It is distinct from the E. coli X-binding adhesins with M and S specificity. A total of 138 E. coli isolates belonging to various serotypes, mostly from urinary tract infections, were screened for the presence of DNA sequences related to the afa operon and for the expression of an X-adhesin able to mediate mannose-resistant hemagglutination (MRHA) and adhesion to uroepithelial cells. Fifteen strains were shown to harbor DNA sequences related to the AFA-I-encoding operon, and 13 of them expressed an X-adhesin. Using as probes different DNA segments of the AFA-I-encoding operon in Southern experiments, we demonstrated that only three of these clinical isolates contained genetic determinants closely related to those identified in the original afa prototype strain (KS52): presence of the afaA, afaB, afaC, afaD, and afaE genes associated with the expression of a 16,000-dalton hemagglutinin-adhesin which strongly cross-reacted with AFA-I-specific antibodies. The other E. coli isolates harbored DNA sequences homologous to the afaA, afaB, afaC, and afaD genes, but lacked the sequence corresponding to the adhesin-producing gene afaE; Western blots allowed the detection of polypeptides (15,000, 15,500, or 16,000 daltons) in these strains which cross-reacted with variable intensity with antibodies raised against the denatured AFA-I protein, but did not cross-react with native AFA-I-specific antibodies. Following DNA cloning experiments from chromosomal DNA of two of those strains (A22 and A30), we demonstrated that although the AFA related operon in A22 and A30 strains lacked the AFA-I adhesin-encoding gene, they synthesized a functional X-adhesin. Thus, strains A22 and A30 encode adhesins designated AFA-II and AFA-III, which were cloned on recombinant plasmids pILL72 and pILL61, respectively. Southern hybridization experiments and Western blot analyses of the 15 AFA-related strains demonstrate the heterogeneity of the genetic sequences encoding the structural adhesin and suggest the bases for the serological diversity of the AFA adhesins. PMID- 2893775 TI - Appearance of sialoglycoproteins in encysting cells of Entamoeba histolytica. AB - Amoeba-bacterium cultures of Entamoeba histolytica transferred to a hypoosmotic medium depleted of nutrients changed morphologically and biochemically. The cells ejected grains of rice starch, rounded up, and formed a distinct cell wall that was resistant to detergent, bound the sialic acid-specific lectin from Limulus polyphemus, and became fluorescent with Calcofluor M2R. A subpopulation of these cells displayed more than one nucleus. All these signs are characteristic of encysting cells and were also observed in cysts obtained from a human patient. The morphological changes were accompanied by the appearance of two new glycoproteins with apparent molecular sizes of 100 and 150 kilodaltons which contained sialic acid. Sialic acid has been reported to be absent from trophozoites of Entamoeba species. The presence of this sugar residue on cyst specific proteins parallels recently reported findings during the encystation of the related reptilian parasite Entamoeba invadens. This may indicate a basic role for sialic acid in the encystation of Entamoeba parasites. PMID- 2893774 TI - Serial isolates of Pseudomonas aeruginosa from a cystic fibrosis patient have identical pilin sequences. AB - Five isolates of Pseudomonas aeruginosa (CD2, CD3, CD4, CD5, and CD10) from a patient with cystic fibrosis were examined with regard to several genotypic and phenotypic characteristics to determine whether the patient was colonized with one or several distinct strains. Isolates CD2, CD3, and CD4 were obtained from a single sputum sample, and CD5 and CD10 were obtained 1 and 2 years later, respectively. On the basis of colonial morphology, serotyping, and antibiograms, the five isolates appeared to be different strains. However, Southern blot analysis with a 1.2-kilobase DNA probe containing the P. aeruginosa PAK pilin gene indicated that all five strains were identical at that genetic locus. The pilin genes of the five isolates were cloned and sequenced at the nucleotide level and found to be identical. Southern blot analysis with a probe from a separate region of the P. aeruginosa chromosome, a 741-base-pair PstI-NruI DNA fragment adjacent to the exotoxin A gene, also revealed genetic identity among these five clinical isolates. On this basis, it was concluded that this patient was colonized with a single strain of P. aeruginosa and that the strain had remained genetically stable over a period of 2 years. The predicted pilin sequence of the CD isolates was almost identical to that of strain PA103 (97% homology) and serologically related to PAO pilin, with which it shared 80% homology. No immunological cross-reactivity was detected between the CD and PAK pilins, which shared the least homology (62%) among the four pilins considered in this study. Although all five CD isolates contained identical pilin genes, three had acquired mutations which prevented normal expression of the pilus system. CD3 was a putative regulatory mutant which was unable to produce normal amounts of pilin, and CD4 and CD10 were putative assembly mutants which produced normal amounts of pilin but were unable to assemble the pilin subunit into intact pili. PMID- 2893776 TI - Agglutinating monoclonal antibodies that specifically recognize lipooligosaccharide A of Bordetella pertussis. AB - Monoclonal antibodies that specifically agglutinate strains of Bordetella pertussis having serotype 1 agglutinogen were uniquely reactive with the electrophoretically slow-migrating A form of lipooligosaccharide. These monoclonal antibodies should be useful for the structural analysis of B. pertussis lipooligosaccharide and for the establishment of a better-defined serogroup for Bordetella species. PMID- 2893777 TI - Simulation of plasma bentazepam levels in multiple dosage regimens from parameters established by non-linear regression and bayesian estimation. AB - In the present study, a simulation was made of the time-course of the plasma levels of bentazepam, administered orally at a dose of 25 mg with dosage intervals of 8, 12 and 24 h over 5 days of treatment. The pharmacokinetic parameters corresponding to a single-compartment model were calculated in a previous study with 10 patients who received the drug in a multiple dosage regimen, using all the data relating to plasma levels even though they corresponded to different administrations, by non-linear regression employing programs based on homoscedastic, heteroscedastic and bayesian estimation methods. The mean values of the kinetic parameters obtained previously and used in the present study were as follows: for the absorption constant, mean values of 2.33, 2.18 and 2.75 h-1 were used; for the elimination constant, the values used were 0.10, 0.09 and 0.22 h-1 and for the apparent distribution volume, the values used were 1.89, 2.89 and 0.80 l/kg, with each of the above-mentioned calculation programs, respectively. The highest value for the maximum concentration at steady state proved to be 313.2 ng/ml for a dosage interval of 8 h according to the parameters established with the program using homoscedastic estimation. In the same case (homoscedastic estimation) the highest value of the minimum at steady state was 168.7 ng/ml. By contrast, the lowest value of the maximum value at steady state--129.3 ng/ml--was obtained with a dosage interval of 24 h using the parameters of the heteroscedastic estimation method, while the lowest value of the corresponding minimum was also observed for an interval of 24 h but using the parameters of the bayesian estimation; this was 2.8 ng/ml. PMID- 2893778 TI - Induction and reduction of muscle tremor upon acute and repeated administration of the beta 2-agonists terbutaline, salbutamol and tulobuterol. AB - Two single-blind placebo-controlled crossover studies on healthy volunteers were performed to compare typical adverse effects of the beta 2-adrenoceptor agonists salbutamol, terbutaline und tulobuterol in a daily period of eight h after acute oral administration of different doses. Assessments were repeated after six days of regular drug intake, to look for habituation phenomena. Finger tremor, integrated surface-EMG in relation to voluntary force, blood pressure and heart rate were measured. Tremor was recorded with a 3-dimensional accelerometer during three different states of hand extensor muscle activity: relaxed, lightly and maximally contracted. The tremor signal was submitted to power spectrum analysis (FFT). All drug effects depended on the dose and the type of drug used, 2 mg tulobuterol being about equivalent to 4 mg salbutamol and to 2.5 mg terbutaline. Cardiovascular adverse effects were weak and transient. The induction of resting tremor showed some habituation across subchronic medication, whereas cumulative and ceiling effects of the beta 2-agonists occurred in respect to tremor during both states of active muscle contraction. However, the beta 2-adrenergic effect during strong contraction consisted in a prominent reduction of tremor. This striking result did not seem to be related to a transient increase of force, relative to myoelectric activity, which was no longer seen after subchronic medication. In case of ceiling effects, the relative changes in tremor intensity decreased with continuous beta 2-sympathomimetic treatment. Therefore, tremor might become a tolerable though inevitable concomitant of bronchodilatory therapy. Its quantitative measurement seems to provide adequate means to assess dose- and time-efficacy as well as to estimate clinical benefit. PMID- 2893779 TI - Hypophysiotrophic thyrotropin releasing hormone (TRH) synthesizing neurons. Ultrastructure, adrenergic innervation and putative transmitter action. AB - The neuropeptide thyrotropin releasing hormone (TRH) is capable of influencing both neuronal mechanisms in the brain and the activity of the pituitary-thyroid endocrine axis. By the use of immunocytochemical techniques, first the ultrastructural features of TRH-immunoreactive (IR) perikarya and neuronal processes were studied, and then the relationship between TRH-IR neuronal elements and dopamine-beta-hydroxylase (DBH) or phenylethanolamine-N methyltransferase (PNMT)-IR catecholaminergic axons was analyzed in the parvocellular subnuclei of the hypothalamic paraventricular nucleus (PVN). In control animals, only TRH-IR axons were detected and some of them seemed to follow the contour of immunonegative neurons. Colchicine treatment resulted in the appearance of TRH-IR material in parvocellular neurons of the PVN. At the ultrastructural level, immunolabel was associated with rough endoplasmic reticulum, free ribosomes and neurosecretory granules. Non-labelled axons formed synaptic specializations with both dendrites and perikarya of the TRH synthesizing neurons. TRH-IR axons located in the parvocellular units of the PVN exhibited numerous intensely labelled dense-core and fewer small electron lucent vesicles. These axons were frequently observed to terminate on parvocellular neurons, forming both bouton- and en passant-type connections. The simultaneous light microscopic localization of DBH or PNMT-IR axons and TRH-synthesizing neurons demonstrated that catecholaminergic fibers established contacts with the dendrites and cell bodies of TRH-IR neurons. Ultrastructural analysis revealed the formation of asymmetric axo-somatic and axo-dendritic synaptic specializations between PNMT-immunopositive, adrenergic axons and TRH-IR neurons in the periventricular and medial parvocellular subnuclei of the PVN. These morphological data indicate that the hypophysiotrophic, thyrotropin releasing hormone synthesizing neurons of the PVN are directly influenced by the central epinephrine system and that TRH may act as a neurotransmitter or neuromodulator upon other paraventricular neurons. PMID- 2893780 TI - HLA-DR alpha, -DX alpha, and DR beta III gene association studies in DR3 individuals. AB - In this study we have examined the results of probing with synthetic oligomers at the DR beta III locus, together with restriction fragment length polymorphisms defined by BglII digestion and a cDNA DR alpha probe, and Taq 1 digestion and a genomic DQ alpha probe. We have demonstrated heterogeneity of the human leukocyte antigen DR3 and close association of the DR alpha, DR beta III, and DX alpha genes. Two DR3-related preferential allelic associations have been identified, which may prove useful in family analysis as well as for investigations of DR3 related diseases. PMID- 2893781 TI - A formyl peptide contracts guinea pig lung: role of arachidonic acid metabolites. AB - We studied the role of cyclooxygenase and lipoxygenase products of arachidonic acid metabolism in mediating N-formyl-methionyl-leucyl-phenylalanine- (FMLP) induced contractions of guinea pig lung parenchymal strips. The cyclooxygenase inhibitors indomethacin (10(-5) M) and aspirin (3 X 10(-5) to 10(-4) M), the lipoxygenase inhibitor nordihydroguaiaretic acid (10(-5) to 3 X 10(-5) M), and the combined cyclooxygenase/lipoxygenase inhibitors 1-phenyl-3-pyrazolidinone (Phenidone) (3 X 10(-5) to 3 X 10(-4) M) and BW 755C (10(-5) to 10(-4) M) each caused a decrease in the maximum force induced by FMLP (Fmax) and an increase in the concentration of FMLP required to produce 50% of Fmax (EC50). The thromboxane synthesis inhibitor imidazole (3 X 10(-3) M) also decreased Fmax. The leukotriene D4 receptor antagonist FPL 55712 (5.7 X 10(-6) to 1.9 X 10(-5) M) increased the EC50 for FMLP, whereas desensitization of lung parenchymal strips to leukotriene B4 by pretreatment with this leukotriene (10(-7) M) had no effect on FMLP-induced contraction. After exposure to FMLP (10(-6) M), guinea pig lung produced (as determined by high-performance liquid chromatography and radioimmunoassay) leukotrienes C4 and B4, thromboxane A2 (as measured by its stable degradation product thromboxane B2), and prostaglandin F2 alpha. Lung strips not exposed to FMLP showed no evidence of leukotriene production. We conclude that thromboxane A2 and leukotriene C4 generated in response to FMLP mediate a substantial fraction of the force induced by this peptide in guinea pig lung parenchymal strips. PMID- 2893783 TI - Enumeration of Clostridium perfringens spores in human feces: comparison of four culture media. AB - Enumeration of Clostridium perfringens spores was compared using 4 culture media. Duplicate 1 g portions of 35 stools (25 from C. perfringens food poisoning outbreaks and 10 from normal stools) were heat treated 20 min at 75 degrees C and tested on tryptose-sulfite-cycloserine (TSC) agar, trypticase-soy-blood (TSB) agar, lactose-sulfite (LS) medium, and iron milk (IM) medium. Dilutions were plated directly onto TSB and TSC, and a 3-tube most probable number determination was made with each specimen in LS and IM incubated at 45 degrees C. TSB was easiest to use and nonhemolytic food poisoning strains were readily differentiated from the normal hemolytic biotype on this medium. Confirmed counts on TSC and TSB were similar for all specimens, but counts of 8 of 25 outbreak specimens were 2-4 log units lower in LS and IM than on plating media; spores in specimens associated with 2 of 5 outbreaks were intolerant of the elevated temperatures. Results showed that elevated temperature MPN methods in LS and IM are inappropriate for the examination of outbreak stools. PMID- 2893782 TI - Nonenzymatic isolation and culture of adult islets from atrophic pancreata of copper-deficient rats: a morphologic analysis. AB - The purpose of this study was to develop a nonenzymatic method of isolating adult islets using atrophied pancreata from copper-deficient rats and to analyze their morphologic characteristics and behavior in culture. This unusual model of isolation was studied because islets remain intact in the course of dietary copper deficiency while the acinar glandular component of the pancreas undergoes selective atrophy and lipomatosis. Small fragments containing islets were readily microdissected from atrophied glands and placed in culture. Within 24 h the fragments congealed into small irregular- to spherical-shaped masses within which the darker profile of islets could be distinguished. Within a period of 3 to 5 d, islet tissue began to bud from the lipocytic mass until by Day 7 spherical aggregates of intact islet tissue separated from the residual fragments. Subsequent to further in vitro treatment, these islets could be maintained as free viable spherical masses if periodically agitated, as attached stationary islets which developed monolayer growth if left undisturbed and as aggregated masses of islet tissue forming megaislets if combined in small groups. Grouped islets treated with actinomycin D and cycloheximide did not exhibit aggregation when incubated with these inhibitors. This suggests that megaislet formation was an active process requiring protein-RNA synthesis rather than passive clumping or aggregation that can accompany metabolically altered or dying islets undergoing cellular shedding and adhesion. Immunohistochemical localization demonstrated that insulin, glucagon, somatostatin, and pancreatic polypeptide-immunoreactive cell types were present within the islets derived from this technique. The cellular topography of these islets was not unlike that described by others for islets cultured from enzymatic isolation. This culture model may serve as a resource for mature, viable islets isolated without mechanical or enzymatic disaggregation which can have attenuating effects on islet function. PMID- 2893784 TI - Food refusal after an incident of choking: a posttraumatic eating disorder. PMID- 2893785 TI - Subdural empyema. PMID- 2893786 TI - Localization and enumeration of fimbria-associated adhesins of Bacteroides loescheii. AB - Monoclonal antibodies that specifically inhibit coaggregation between Bacteroides loescheii PK1295 and its two gram-positive partners Streptococcus sanguis 34 and Actinomyces israelii PK14 were used to enumerate and localize two distinct types of fimbria-associated adhesins on the surface of B. loescheii. Binding studies with radiolabeled monoclonal antibodies indicated that a maximum (Bmax calculated from Scatchard plots) of approximately 400 adhesin molecules specific for S. sanguis and 310 adhesin molecules specific for A. israelii reside on the surface of the cell. Immunoelectron microscopy revealed that the adhesins were not an integral part of the fimbrial subunit; rather, they were usually found on the distal portion of the structures arranged in a random fashion. PMID- 2893788 TI - Binding properties of 9K protein to F1-ATPase: a counterpart ligand to the ATPase inhibitor. AB - A regulatory subunit of yeast mitochondrial ATP synthase, 9K protein, formed an equimolar complex with F1-ATPase in the presence of ATP and Mg2+, indicating that the binding of the protein to the enzyme took place in a similar manner to that of ATPase inhibitor. The ATP-hydrolyzing activity of F1-ATPase decreased 40% on binding of the 9K protein, and the remaining activity was resistant to external ATPase inhibitor. The apparent dissociation constant of the F1-ATPase-9K complex was determined by gel permeation chromatography to be 3.7 X 10(-6) M, which was in the same order of magnitude as that of enzyme-ATPase inhibitor complex (4.2 x 10(-6) M). When added simultaneously the binding of the inhibitor and 9K protein to F1-ATPase were competitive and the sum of their bindings did not exceed 1 mol per mol of enzyme. However, the binding of each protein ligand to F1-ATPase took more than 1 min for completion, and when one of these two proteins was added 10 min after the other, it did not replace the other. These observations strongly suggest that membrane-bound F1-ATPase always binds to either the 9K protein or ATPase inhibitor in intact mitochondria and that the complexes with the two ligands are active and inactive counterparts, respectively. PMID- 2893789 TI - The H+-translocating ATP synthase in Halobacterium halobium differs from F0F1 ATPase/synthase. AB - Cell envelope vesicles of Halobacterium halobium synthesize ATP by utilizing base acid transition (an outside acidic pH jump) under optimal conditions (1 M NaCl, 80 mM MgCl2, pH 6.8) even in the presence of azide (a specific inhibitor of F0F1 ATPase) (Mukohata & Yoshida (1987) J. Biochem. 101, 311-318). An azide insensitive ATPase was isolated from the inner face of the vesicle membrane, and shown to hydrolyze ATP under very specific conditions (1.5 M Na2SO4, 10 mM MnCl2, pH 5.8) (Nanba & Mukohata (1987) J. Biochem. 102, 591-598). This ATPase activity could also be detected when the vesicle components were solubilized by detergent. The relationship between ATP synthesis and the membrane-bound ATPase was investigated by modification of the vesicles with 7-chloro-4-nitrobenzo-2-oxa-1,3 diazole (NBD-Cl) or N-ethylmaleimide (NEM). The inhibition pattern of ATP synthesis in the modified vesicles and that of ATP hydrolysis of the solubilized modified vesicles were compared under the individual optimum conditions. The inhibition patterns were almost identical, suggesting that the ATP synthesis and hydrolysis are catalyzed by a single enzyme complex. The ATP synthase includes the above ATPase (300-320 kDa), which is composed of two pairs of 86 and 64 kDa subunits. This is a novel H+-translocating ATP synthase functioning in the extremely halophilic archaebacterium. This "archae-ATP-synthase" differs from F0F1-ATPase/synthase, which had been thought to be ubiquitous among all respiring organisms on our biosphere. PMID- 2893787 TI - Autolysis-resistant peptidoglycan of anomalous composition in amino-acid-starved Escherichia coli. AB - Nongrowing Escherichia coli deprived of an essential amino acid continued to produce peptidoglycan at a rate approximately 30% of that of growing cells. The composition of this peptidoglycan was very different from that of growing cells and resembled that of peptidoglycan left undegraded during partial autolysis of the bacteria. Synthesis of this peptidoglycan of anomalous composition began at once upon the removal of the amino acid from the medium. Fifteen minutes of amino acid deprivation was sufficient to virtually completely prevent penicillin induced autolytic wall degradation in vivo. During this time, although the specific activities of soluble and membrane-bound hydrolytic transglycosylases and endopeptidases remained high, the peptidoglycan produced showed decreased sensitivity to degradation in vitro. After more extensive (2-h) starvation, triggering of autolysis by chaotropic agents was also blocked. Autolysis in growing cells may be selective for peptidoglycan representing the cylindrical portion of the sacculus. It is suggested that at least part of the mechanism of the well-known lysis resistance of nongrowing E. coli is related to the deposition of structurally anomalous and relatively autolysin-resistant peptidoglycan at some strategically located sites on the bacterial surface. PMID- 2893790 TI - Single-site catalysis of F1-ATPase from thermophilic bacterium PS3 and its dominance in steady-state catalysis at low ATP concentration. AB - Single-site catalysis by F1-ATPase from a thermophilic bacterium PS3 (TF1) was examined by incubating the enzyme with a submolar amount of radioactive ATP. The profile of single-site catalysis by TF1 at 23 degrees C was different from that of beef heart mitochondrial F1-ATPase (MF1). ATP hydrolysis on the enzyme and release of the products was rapid, and subsequent addition of non-radioactive ATP (cold chase) did not promote the hydrolysis of radioactive ATP, indicating that the rate-limiting step was not the step of product release but the step of ATP binding to the enzyme. Thus, the characteristic features of so-called uni-site catalysis were not observed. At 60 degrees C, whether in the presence or absence of phosphate ion, a small amount of bound [alpha, gamma-32P]ATP and cold chase promotion were observed. However, since bound 32P1 was not detected by centrifugal gel filtration, it is not yet certain whether TF1 has typical uni site characteristics. Based on the hydrolytic turnover rate for single-site catalysis and analysis of the kinetics of steady-state catalysis, it is proposed that single-site catalysis is dominant even in steady-state catalysis at ATP concentrations of less than about 20 microM. PMID- 2893791 TI - Human skeletal muscle contains two major aminopeptidases: an anion-activated aminopeptidase B and an aminopeptidase M-like enzyme. AB - Two major aminopeptidases, an aminopeptidase B and an aminopeptidase M-like enzyme, were purified from human skeletal muscle by DEAE-cellulose, HPLC gel filtration, and hydroxyapatite column chromatographies. The purified aminopeptidase B exhibits a molecular weight of 76,000 under both native and denaturing conditions. The activity of the aminopeptidase B is regulated by C1 ions and other anions in vitro. On the other hand, the aminopeptidase M-like enzyme is a monomeric protein having a molecular weight of 96,000. It is capable of significantly cleaving Phe-, Leu-, Arg-, and Ala-aminoacyl bonds in the presence of 2-mercaptoethanol. The pH optima for both enzymes are around 7.0, and bestatin is an effective inhibitor of both enzymes. PMID- 2893792 TI - Interaction of Bordetella pertussis adenylate cyclase with calmodulin. Identification of two separated calmodulin-binding domains. AB - The structural organization of Bordetella pertussis adenylate cyclase was examined by limited proteolysis with trypsin and/or cross-linking with azido calmodulin a photoactivable derivative of its activator, calmodulin (CaM). Adenylate cyclase (which consists of three structurally related peptides of 50, 45, and 43 kDa as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) formed a 1:1 complex with CaM or azido-CaM. CaM-bound adenylate cyclase was cleaved by trypsin into two separate trypsin-resistant fragments of 25 and 18 kDa which both interacted with CaM as judged by their ability to be cross-linked with azido-CaM. These two fragments remained associated with CaM in a catalytically active conformation resembling that of the undigested complex. When proteolysis was carried out in the absence of CaM, the adenylate cyclase was completely inactivated in less than 3 min. Sodium dodecyl sulfate-polyacrylamide gel revealed a single 24-kDa trypsin-resistant fragment. Since this fragment cannot be cross-linked with azido-CaM we suggest that the CaM-binding site on the 25-kDa moiety of the adenylate cyclase is located on a short segment of 1 kDa. PMID- 2893794 TI - Glutamate biosynthesis in Bacillus azotofixans. 15N NMR and enzymatic studies. AB - Pathways of ammonia assimilation into glutamic acid in Bacillus azotofixans, a recently characterized nitrogen-fixing species of Bacillus, were investigated through observation by NMR spectroscopy of in vivo incorporation of 15N into glutamine and glutamic acid in the absence and presence of inhibitors of ammonia assimilating enzymes, in combination with measurements of the specific activities of glutamate dehydrogenase, glutamine synthetase, glutamate synthase, and alanine dehydrogenase. In ammonia-grown cells, both the glutamine synthetase/glutamate synthase and the glutamate dehydrogenase pathways contribute to the assimilation of ammonia into glutamic acid. In nitrate-grown and nitrogen-fixing cells, the glutamine synthetase/glutamate synthase pathway was found to be predominant. NADPH-dependent glutamate dehydrogenase activity was detectable at low levels only in ammonia-grown and glutamate-grown cells. Thus, B. azotofixans differs from Bacillus polymyxa and Bacillus macerans, but resembles other N2-fixing prokaryotes studied previously, as to the pathway of ammonia assimilation during ammonia limitation. Implications of the results for an emerging pattern of ammonia assimilation by alternative pathways among nitrogen-fixing prokaryotes are discussed, as well as the utility of 15N NMR for measuring in vivo glutamate synthase activity in the cell. PMID- 2893793 TI - Primary structure of chicken liver acetyl-CoA carboxylase deduced from cDNA sequence. AB - The complete amino acid sequence of acetyl-CoA carboxylase from chicken liver has been deduced by cloning and sequence analysis of DNA complementary to its messenger RNA. The results were confirmed by Edman degradation of peptide fragments obtained by digestion of the enzyme polypeptide with Achromobacter proteinase I or staphylococcal serine proteinase. Chicken liver acetyl-CoA carboxylase is predicted to be composed of 2,324 amino acid residues, having a calculated molecular weight of 262,706. The biotin carboxyl carrier protein domain is located in the middle region of the enzyme polypeptide. The amino terminal portion of the acetyl-CoA carboxylase has been found to exhibit a homologous primary structure to that of carbamyl phosphate synthetase. Localization of possible functional domains including biotin carboxylase subsite in the acetyl-CoA carboxylase polypeptide is discussed. PMID- 2893795 TI - The regulatory and catalytic subunits of cAMP-dependent protein kinases are associated with transcriptionally active chromatin during changes in gene expression. AB - Changes in the association of the catalytic subunit and the regulatory subunits of isozymes I and II of cAMP-dependent protein kinases (RI and RII, respectively) with the transcriptionally active chromatin fraction from rat liver were examined after a glucagon/theophylline injection and also after partial hepatectomy. Chromatin was partitioned into transcriptionally active and bulk, transcriptionally inactive fractions by digestion with micrococcal nuclease under appropriate conditions. In both experimental models, an increased content of catalytic and both RI and RII subunits was observed in chromatin fractions that were enriched in transcriptionally active DNA, particularly in the fraction associated with the residual nuclear matrix-lamina. The changes in the association of the subunits with these fractions paralleled the increases in intracellular cAMP levels and occurred in a time frame compatible with the changes in gene expression. The catalytic subunits could be removed from the nuclear matrix-lamina fraction by salt, whereas the two regulatory subunits remained tightly bound. The data support the concept of a direct role of the regulatory subunits of cAMP-dependent protein kinases in the induction of gene expression. However, we were unable to confirm that RII possessed an intrinsic topoisomerase activity. PMID- 2893796 TI - Secondary structure of the Neurospora crassa plasma membrane H+-ATPase as estimated by circular dichroism. AB - In a previous communication, a water-soluble, hexameric form of the Neurospora crassa plasma membrane H+-ATPase was described (Chadwick, C. C., Goormaghtigh, E., and Scarborough, G. A. (1987) Arch. Biochem. Biophys. 252, 348-356). To facilitate physical studies of the hexamers, the H+-ATPase isolation procedure has been improved, resulting in a structurally and functionally stable hexamer preparation that contains only 5 to 10% non-ATPase protein, approximately 12 mol of enzyme-bound lysophosphatidylcholine/mol of H+-ATPase monomer, and little or no residual plasma membrane phospholipid. Importantly, when activated by lysophosphatidylglycerol, which satisfies the acidic phospholipid requirement of the enzyme, the hexameric quaternary structure of the enzyme is retained, indicating that the functional properties of the water-soluble hexamers are relevant to those of the native, membrane-bound enzyme. The circular dichroism (CD) spectrum of this H+-ATPase preparation has been measured from 184 to 260 nm and used to estimate the secondary structure of the enzyme. The H+-ATPase is estimated to consist of approximately 36% helix, 12% antiparallel beta-sheet, 8% parallel beta-sheet, 11% beta-turn, and 26% other (irregular) structure. There is no change in the CD spectrum when known enzyme ligands are added to the H+-ATPase solution, suggesting that any changes in secondary structure that might occur during ligand binding and/or catalytic cycling are either minor or result in compensatory changes in secondary structure. The CD spectrum of the H+-ATPase is also compared to published spectra of the animal cell Na+/K+- and Ca2+-ATPases and is shown to be quite similar in shape and intensity, suggesting that all of these ATPases, which have significant sequence homology and are mechanistically similar, may have similar secondary structure composition as well. PMID- 2893797 TI - Different secretory pathways of renin from mouse cells transfected with the human renin gene. AB - Mammalian cells in culture, transfected with human renin gene, can provide a useful tool for studying renin biosynthesis and secretion. We transfected fibroblast cells (mouse L929 and Chinese hamster ovary cells) and pituitary tumor cells (mouse AtT-20) with the human renin gene and a selectable plasmid (pSV2Neo). Transfected fibroblasts synthesize prorenin only. Prorenin is secreted by fibroblasts constitutively and the secretion is not influenced by 8-bromo cAMP. On the other hand, transfected AtT-20 cells synthesized both prorenin and mature active renin. Transfected AtT-20 cells release prorenin by constitutive secretion but mature renin is secreted by a regulated mechanism since the secretion of the former is not influenced by 8-bromo-cAMP but the release of the latter is significantly stimulated. Our studies demonstrate that human renin may be secreted by at least two cellular pathways: prorenin by a constitutive pathway and mature renin by a regulated pathway. These transfected cells may provide useful models for studies of human renin synthesis, processing, and secretion. PMID- 2893798 TI - Intracellular processing of cytidylyltransferase in Krebs II cells during stimulation of phosphatidylcholine synthesis. Evidence that a plasma membrane modification promotes enzyme translocation specifically to the endoplasmic reticulum. AB - After a 3-h incubation of Krebs II ascitic cells in the presence of phospholipase C from Clostridium welchii under nonlytic conditions, the incorporation of [3H] choline into phosphatidylcholine was increased 1.7-fold as compared to untreated cells. The total amounts of phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin were unchanged up to 3 h of incubation. The limiting step in phosphatidylcholine biosynthesis was the formation of CDP-choline catalyzed by CTP:choline-phosphate cytidylyltransferase (EC 2.7.7.15) as monitored by the decrease in phosphocholine labeling following phospholipase C treatment of cells prelabeled with [3H]choline. The specific activity of homogenate cytidylyltransferase was increased about 1.6-fold in phospholipase C-treated cells. Specific activity of the membrane fraction was increased 2-fold, whereas cytosolic specific activity decreased in phospholipase C-treated cells. The activation of cytidylyltransferase was concomitant with translocation of the enzyme from the cytosol to the membrane fraction. The latter was further fractionated using a Percoll gradient that allowed an efficient separation between endoplasmic reticulum and other subcellular membranes. In control cells, particulate cytidylyltransferase activity co-migrated with the endoplasmic reticulum and ribosome markers and not with the plasma membrane. Also, in treated cells, the stimulation of cytidylyltransferase activity occurred at the endoplasmic reticulum level and did not involve either the external cell membrane or other cellular organelles including the Golgi apparatus, lysosomes, or mitochondria. Thus, our results demonstrate that a stimulus acting on the plasma membrane promotes the translocation of the soluble form of cytidylyltransferase specifically to the endoplasmic reticulum. PMID- 2893799 TI - Secondary structural analyses of the nicotinic acetylcholine receptor as a test of molecular models. AB - Circular dichroism (CD) spectroscopy was used to determine that the secondary structure of purified nicotinic acetylcholine receptor (AChR) of Torpedo californica in both reconstituted vesicles and a cholate-solubilized state is, on average, 23% alpha-helix, 43% beta-sheet, 6% beta-turn, and 28% random coil. These data can serve to test models by placing limits on the particular types of secondary structural motifs which make up the receptor. A number of models proposed for the AChR are discussed in relation to the experimental data presented. Additionally, the protein in both vesicle and solubilized environments was exposed to an agonist, carbamylcholine, or a competitive antagonist, hexamethonium, to monitor net conformational changes upon ligand binding. The protein secondary structure was not changed upon solubilization, nor was any large net conformational change observed upon ligand binding, although small local or compensatory changes cannot be ruled out. PMID- 2893800 TI - Icosanoid production can be decreased without alterations in cellular arachidonate content or enzyme activities required for arachidonate release and icosanoid synthesis. AB - We have demonstrated that icosanoid production can be inhibited by altering the distribution of arachidonate within the cell, so that it is not released from phospholipids for icosanoid synthesis. This effect was observed in a prostaglandin E2-producing cell line (HSDM1C1) by deprivation of exogenous arachidonate for 24-48 h. Icosanoid production by the cells upon bradykinin stimulation was impaired despite no change in the concentration of arachidonate within the cell and no change in the activity of cyclooxygenase, phospholipases, acyltransferases, or fatty acyl-CoA hydrolase. Associated with the decline in prostaglandin E2 production was an increase in arachidonate incorporation into ethanolamine plasmalogens and a decrease in the activity of the enzyme arachidonoyl-CoA synthetase, which may play a role in compartmentation of arachidonate within the cell. Thus, we have found that a decrease in icosanoid production can be achieved without pharmacologic intervention by a short-term restriction of exogenous arachidonate which leads to redistribution of arachidonate within phospholipids and/or subcellular membranes in the cell. PMID- 2893801 TI - Decreased hepatic fatty acid oxidation at weaning in the rat is not linked to a variation of malonyl-CoA concentration. AB - In rats weaned on a high-carbohydrate diet, hepatic fatty acid oxidation capacity is decreased when compared to suckling rats. Previous studies (Benito et al., 1979) suggested that a malonyl-CoA-dependent mechanism could be at the origin of this decrease. Studies on isolated hepatocytes show that despite, respectively, a low and a high lipogenic rate in suckling and weaned rats, malonyl-CoA concentrations are similar in the two groups. This might be due to the lower ratio fatty acid synthetase/acetyl-CoA carboxylase (EC 6.4.1.2) activities during suckling than after weaning. Different rates of hepatic fatty acid oxidation despite similar malonyl-CoA concentrations can be explained by the 2.5-fold higher carnitine palmitoyltransferase I (EC 2.3.1.21) activity in suckling rats together with a 7-fold higher Ki for malonyl-CoA. This precludes a tight control of fatty acid oxidation by [malonyl-CoA] in suckling rats. Weaning on a high-fat carbohydrate-free diet abolishes the changes previously described for the kinetic characteristics of carnitine palmitoyltransferase I suggesting that nutritional modifications rather than a developmental stage are involved. Thus, during the suckling-weaning transition, a variation of [malonyl-CoA] is not responsible for the decrease in hepatic fatty acid oxidation. It involves, in addition, a decrease in carnitine palmitoyltransferase I activity and an increase of the sensitivity of this enzyme to malonyl-CoA. PMID- 2893802 TI - Inhibition of endocytosis from coated pits by acidification of the cytosol. AB - Binding and endocytosis of the ligands transferrin, epidermal growth factor (EGF), and ricin were measured in a number of different cell lines after treatment of cells with compounds that react with SH-groups and under conditions where the cytosolic pH was lowered. N-ethylmalemide and diamide irreversibly inhibited endocytosis of all ligands tested, whereas low pH in the cytosol strongly inhibited endocytosis of transferrin and EGF. Data obtained by electron microscopy indicated that the formation of coated vesicles from coated pits is inhibited in acidified cells. Entry of ricin was much less affected, and ricin endocytosed under these conditions was able to intoxicate the cells. At low pH in the cytosol there was a calcium-dependent increase in the number of transferrin receptors at the cell surface. The increase was even larger in the presence of the calcium ionophore A23187, whereas it was completely blocked by the calmodulin antagonists trifluoperazine and W7. The results show that endocytosis from coated pits can be inhibited in a reversible way by acidification of the cytosol and they suggest that a second pathway of endocytosis exists, possibly involving formation of vesicles from uncoated areas of the membrane. PMID- 2893803 TI - Column liquid chromatographic determination of hydrolysed bopindolol, in the picogram per millilitre range in plasma, using cartridge extraction and dual electrochemical detection. AB - A highly sensitive and specific column liquid chromatographic assay with electrochemical detection was developed for hydrolysed bopindolol, an active metabolite of bopindolol (Sandonorm) in human plasma. The pre-chromatographic sample preparation involved Extrelut column clean-up followed by liquid extraction of the organic extract into dilute acetic acid. Separation was on a Nucleosil ODS 3-microns column at 40 degrees C, with a phosphate buffer-methanol mobile phase. Detection was performed at +450 mV with an ESA electrochemical detector. Mepindolol was used as internal standard and quantitation was based on peak-area ratios. Total analysis time was 14 min per sample. The recovery rate of the assay was at least 70% for both compounds. A detection limit as low as 25 pg/ml, starting with 1 ml of plasma, was achieved. The day-to-day reproducibility and accuracy, checked with quality-control samples, demonstrated the reliability of this assay used by different analysts, on different chromatographic systems and over a long period of time. PMID- 2893804 TI - Quantitation of effects of subinhibitory concentrations of trimethoprim on P fimbria expression and in vitro adhesiveness of uropathogenic Escherichia coli. AB - The ability to adhere to and colonize urogenital mucosa is an important virulence attribute of uropathogenic Escherichia coli. This adherence, which appears to be mediated by P fimbriae, may be affected by antibiotics or other agents that affect fimbrial expression. We describe here an enzyme immunofiltration assay to quantitate fimbriation and the application of that technique to measurement of the effects of sublethal doses of trimethoprim on P fimbrial expression. Effects on P fimbriation correlated with effects on the adherence of treated bacteria to cultured T24 bladder carcinoma epithelial cells; i.e., trimethoprim treatment decreased both P fimbriation and bacterial adherence. It was possible to quantitate effects on P fimbriation when type 1 fimbriae were also present. The enzyme immunofiltration assay may be useful for studies on the role of fimbriae in the pathogenesis of bacterial infections, and it may facilitate identification of antimicrobial agents that interfere with bacterial adherence to mucosal surfaces. PMID- 2893805 TI - Enzyme-linked immunosorbent assay for quantitation of attachment and ingestion stages of bacterial phagocytosis. AB - Research on phagocytosis of bacteria is often hampered by the inability to distinguish quantitatively between bacteria that have been ingested by phagocytic cells and those which are attached to the surface of the cells. A method using the enzyme-linked immunosorbent assay technique to simply and accurately measure the rate of bacterial ingestion by phagocytic cells is described. The method is based on the ability of antibacterial antibodies to bind to bacteria attached to but not internalized by phagocytic cells. The attached bacteria were quantitated by enzyme-linked immunosorbent assay. Compared with the number of bacteria at zero time (17 bacteria attached per phagocyte) only 10 to 20% of the bacteria remained attached to phagocytic cells after incubation for 30 min at 37 degrees C. The decrease in detected attached bacteria at 37 degrees C was due to internalization of the bacteria by phagocytic cells, since upon disruption of the monolayer, most of the ingested bacteria were recovered, and at 4 degrees C, most of the bacteria remained extracellularly attached. The proposed attachment and ingestion assay is easy to perform, allows the detection of specific attachment of test bacteria, and provides objective quantitation of attached and ingested bacteria. Most importantly, the assay allows testing of ingestion rates of bacteria under many variables on the same day. PMID- 2893806 TI - Production and characterization of monoclonal antibodies directed against Bordetella pertussis lipopolysaccharide. AB - Hybrid cell lines producing monoclonal antibodies against Bordetella pertussis lipopolysaccharide (LPS) were established. The specificity of the antibodies was ascertained by enzyme-linked immunosorbent assay (ELISA) and ELISA-inhibition experiments with LPS and delipidated polysaccharide fragments (PS-1 and PS-2) prepared from B. pertussis LPS. Monoclonal antibody 9-1-H5 reacted with B. pertussis LPS only, whereas monoclonal antibodies 6-4-H6 and 9-2-A8 reacted with PS-1 and PS-2 as well as B. pertussis LPS. The antibodies did not react with LPS prepared from B. parapertussis and B. bronchiseptica in an LPS-specific ELISA. A monoclonal antibody-based sandwich ELISA was developed for detection of B. pertussis LPS. This assay had a detection limit of B. pertussis LPS in concentrations ranging from 0.16 to 0.32 microgram/ml. The assay was also shown to be specific for the detection of whole B. pertussis bacteria. No cross reactions were observed with strains of Branhamella catarrhalis, Neisseria meningitidis, Streptococcus miteor, Haemophilus influenzae, or Legionella pneumophila. The monoclonal antibodies might be useful for the detection of soluble antigens and whole bacteria in clinical samples and for studies of the immunochemical structure of B. pertussis LPS. PMID- 2893807 TI - Comparative studies of commercially available particle agglutination assay and enzyme-linked immunosorbent assay for screening of human T-cell leukemia virus type I antibodies in blood donors. AB - Human T-cell leukemia virus type I (HTLV-I) transmission during blood transfusion can be prevented by screening for and eliminating blood containing anti-HTLV-I antibodies. For this purpose, we evaluated two commercial test kits for HTLV-I antibodies, Serodia-ATLA (particle agglutination assay [PA]) and Eitest-ATL (enzyme-linked immunosorbent assay [ELISA]), by using serum samples from Japanese blood donors. Of 2,316 serum samples, 39 (1.7%), 34 (1.5%), and 28 (1.2%) were positive for the antibody by PA, ELISA, and immunofluorescence (IF), respectively. The coincidence rate for antibody-positive and antibody-negative results was 99.5% between PA and IF, whereas it was 99.6% between ELISA and IF. The serum samples which were positive by IF were also positive by PA, whereas 2 of 26 IF-positive samples were negative by ELISA. All the samples positive by both PA and ELISA were shown to be positive by IF unequivocally. The samples positive by only one of the two methods (PA or ELISA) were different. Eleven and eight serum samples that were negative by IF but positive by PA and ELISA, respectively, were further studied for HTLV-I antibody by radioimmunoprecipitation. Three of the former but none of the latter were found to be positive for antibody. Moreover, a PA-positive but IF-negative serum sample was shown to have significantly decreased PA titers after 2-mercaptoethanol treatment. The PA was further shown to detect not only IgG antibody but also IgM antibody to HTLV-I after separation of this serum sample by high-performance liquid chromatography. PMID- 2893809 TI - Defect in biosynthesis of mitochondrial acetoacetyl-coenzyme A thiolase in cultured fibroblasts from a boy with 3-ketothiolase deficiency. AB - The etiology of 3-ketothiolase deficiency has been attributed to a defect of mitochondrial acetoacetyl-CoA thiolase because the acetoacetyl-CoA thiolase activity in related materials is not activated by K+, a property characteristic for this enzyme. We studied the enzyme protein and the biosynthesis of mitochondrial acetoacetyl-CoA thiolase, using cultured skin fibroblasts from a 5 yr-old boy with 3-ketothiolase deficiency. The following results were obtained. (a) Activation of acetoacetyl-CoA thiolase activity by K+ was nil; (b) The enzyme activity was not affected by treatment with the antibody against mitochondrial acetoacetyl-CoA thiolase; (c) A signal for mitochondrial acetoacetyl-CoA thiolase protein was not detected in the immunoblot analysis; and (d) Pulse-chase experiments of skin fibroblasts, using [35S]methionine, revealed no incorporation of radioactivity into this enzyme. Therefore, fibroblasts from this patient lacked mitochondrial acetoacetyl-CoA thiolase protein due to a defect in its biosynthesis. PMID- 2893810 TI - Binding sites in the rat brain for Escherichia coli S fimbriae associated with neonatal meningitis. AB - Escherichia coli strains that cause sepsis and meningitis in neonatal infants carry S fimbriae that bind to sialyl galactoside units of cell surface glycoproteins. To investigate the possible role of S fimbriae in determining the tissue tropism of neonatal meningitis, we have studied the presence of binding sites for S fimbriae in different tissues of the neonatal rat which is susceptible to meningitis caused by S-fimbriated E. coli. Purified S fimbriae were incubated on cryostat sections of different rat organs and their binding was assessed by indirect immunofluorescence. In the brain of the neonatal rat, S fimbriae specifically bound to the luminal surfaces of the vascular endothelium and of the epithelium lining the choroid plexuses and brain ventricles. The binding was completely inhibited by the trisaccharide NeuAc alpha 2-3Gal beta 1 4Glc, a receptor analogue of S fimbriae, and by a preceding neuraminidase treatment of the sections. A recombinant E. coli strain expressing S fimbriae adhered in large numbers to the same tissue sites in the neonatal brain sections as did the purified fimbriae, whereas the non-fimbriated host strain and a recombinant strain expressing P fimbriae did not adhere to brain tissues. The results suggest that adhesion of S-fimbriated bacteria to the binding sites observed in the neonatal brain has a pathogenetic role during bacterial invasion from circulation into the cerebrospinal fluid. PMID- 2893808 TI - Effects of beta-adrenergic blockade on verapamil-responsive and verapamil irresponsive sustained ventricular tachycardias. AB - To assess effects of beta-adrenergic blockade on ventricular tachycardia (VT) of various mechanisms, electrophysiology studies were performed before and after intravenous infusion of propranolol (0.2 mg/kg) in 33 patients with chronic recurrent VT, who had previously been tested with intravenous verapamil (0.15 mg/kg followed by 0.005 mg/kg/min infusion). In the verapamil-irresponsive group, 10 patients (group IA) had VT that could be initiated by programmed ventricular extrastimulation and terminated by overdrive ventricular pacing, and 11 patients (group IB) had VT that could be provoked by isoproterenol infusion (3-8 micrograms/min) but not by programmed electrical stimulation, and that could not be converted to a sustained sinus rhythm by overdrive ventricular pacing. Notably, in the group IA patients, all 10 patients had structural heart disease (coronary arteriosclerosis or idiopathic cardiomyopathy); beta-adrenergic blockade accelerated the VT rate in one patient but exerted no effects on the VT rate in the remaining 9 patients, and VT remained inducible in all 10 patients. By contrast, in the group IB patients, 7 of the 11 patients had no apparent structural heart disease; beta-adrenergic blockade completely suppressed the VT inducibility during isoproterenol infusion in all 11 patients. There were 12 patients with verapamil-responsive VT (group II). 11 of the 12 patients had no apparent structural heart disease. In these patients, the initiation of VT was related to attaining a critical range of cycle lengths during sinus, atrial-paced or ventricular-paced rhythm; beta-adrenergic blockade could only slow the VT rate without suppressing its inducibility. Of note, 14 of the total 33 patients had exercise provocable VT: two in group IA, five in group IB, and seven in group II. Thus, mechanisms of VT vary among patients, and so do their pharmacologic responses. Although reentry, catecholamine-sensitive automaticity, and triggered activity related to delayed afterdepolarizations are merely speculative, results of this study indicate that beta-adrenergic blockade is only specifically effective in a subset group (group IB) of patients with VT suggestive of catecholamine-sensitive automaticity. PMID- 2893811 TI - Evidence supporting the identity in Graves' disease of thyroid-stimulating antibody and thyroid growth-promoting immunoglobulin G as assayed in FRTL5 cells. AB - This paper addresses the question: in Graves' disease is there a thyroid-growth stimulating IgG (TGI) separate from thyroid-stimulating antibody (TSAb)? Using the functioning rat thyroid line (FRTL5) cells for TGI (incorporation of [3H] thymidine into DNA) and TSAb (increase in cAMP concentration) assays, we tested IgG from 30 Graves' patients. Positive TGI assay occurred only if cAMP increased in the cells and responses correlated, i.e., r = 0.95, P less than 0.001. With one very potent TSAb-IgG we showed that Fab was active as TGI and TSAb, IgG with pI of 8.5-9.0 was the most potent fraction in both systems and an inhibitory IgG prevented the action of both TSAb-IgG and TSH in both the TSAb and TGI assays. In the last example, the action was on the cell membrane and not on the TSH or IgG. These data are entirely compatible with the view that in Graves' disease, at least as tested in FRTL5 cells, the same IgG is active in stimulating both growth and adenylate cyclase. PMID- 2893812 TI - Antigen CD34+ marrow cells engraft lethally irradiated baboons. AB - The CD34 antigen is present on 1-4% of human marrow cells including virtually all hematopoietic progenitors detected by in vitro assays. Since the anti-CD34 monoclonal antibody 12-8 reacts with a similar marrow population in baboons, it was possible to test whether this antigen is expressed by stem cells responsible for hematopoietic reconstitution in vivo. CD34+ cells were enriched from marrows of five baboons using avidin-biotin immunoadsorption. After lethal irradiation, the five animals were given 15-27 X 10(6) autologous marrow cells (3.2-4.4 X 10(6) cells/kg) containing 65-91% CD34+ cells. All animals achieved granulocyte counts greater than 1,000/mm3 and platelet counts greater than 20 X 10(3)/mm3 by 13-24 d posttransplant and subsequently developed normal peripheral blood counts. Two additional animals received 184 and 285 X 10(6) marrow cells/kg depleted of CD34+ cells. One animal died at day 29 without engraftment, while the other had pancytopenia for greater than 100 d posttransplant. The data suggest that stem cells responsible for hematopoietic reconstitution are CD34+. PMID- 2893814 TI - Bevantolol disposition in patients with hepatic cirrhosis. AB - Bevantolol is a new, cardioselective beta-receptor antagonist that undergoes extensive hepatic biotransformation. To evaluate changes in the disposition of bevantolol produced by liver disease, a single 200-mg oral dose of bevantolol was administered in ten patients who had hepatic cirrhosis and to ten age-matched controls. Cirrhotic patients had a greater plasma bevantolol half-life (6.9 +/- 4.0 hr, mean +/- SD) then did patients with normal liver function (2.8 +/- 1.1 hr, P less than .01), and they also had a longer duration of significant bevantolol-induced heart rate slowing (for 12 hours after oral dose in cirrhotics versus three hours for controls). On the other hand, the peak concentration after the oral dose and the magnitude of bradycardiac effect were similar for both groups. Plasma bevantolol half-life was more variable in cirrhotic patients than in controls. Some of this variability among cirrhotics was attributable to age, which was a significant determinant of bevantolol half-life in the cirrhotic (but not in the control) patient sample. These results indicate that hepatic cirrhosis alters the disposition of bevantolol and suggest that modifications in bevantolol dose should be considered when using this drug to treat patients with liver disease. PMID- 2893813 TI - Characterisation of connective tissue cells containing factor XIII subunit a. AB - Paraffin embedded sections of human liver, lymph node, and placenta showed that certain connective tissue cells were positive for factor XIII subunit a. These cells were further characterised by double immunofluorescence labelling and by combined immunofluorescence and enzyme cytochemical staining on frozen sections. They were labelled by the monoclonal antibodies RFD7 and anti-Leu M3 (markers of the macrophage cell line) but gave a negative reaction for the fibroblast marker IIG10 and showed no alkaline phosphatase activity. Immunoblotting detected factor XIII subunit a in macrophages isolated from placenta but not in human fibroblasts. At lower dilutions, the commercially available antibody against the b subunit of factor XIII also positively reacted with the same cell population. The facts that immunoblotting showed that the antiserum crossreacted with the a subunit and that placental macrophages did not stain strongly for the b subunit also indicate that this antigen is not present in adult connective tissue cells. PMID- 2893816 TI - Distribution of catecholaminergic cells in the retina of the rat, guinea pig, cat, and rabbit: independence from ganglion cell distribution. AB - By using an antibody against tyrosine hydroxylase (TH), the rate-limiting enzyme in the production of catecholamines, we have examined the morphology and distribution of catecholaminergic cells in the retinas of the rat, guinea pig, cat, and rabbit. In the albino rat, as reported by others, most TH-immunoreactive (TH-IR) cells were amacrine cells, and formed two morphological classes. Cells of one class (class 1) are stellate amacrine cells, the somata of most being in the inner part of the inner nuclear layer (INL). Cells of the second class (class 2) were seen only as small somata, also in the inner part of the INL. Cells of both classes were found in all areas of the retina, with a distinct but broad concentration around the superior-temporal margin of the retina. A small number of TH-IR interplexiform cells was seen. In the pigmented rat, only class 1 cells were recognized, also concentrating at the superior-temporal margin. In the guinea pig, cat, and rabbit, TH-IR cells also seemed to form one morphological class of amacrine cells, which resembled the class 1 cells of the albino rat. In the guinea pig and cat, their distribution resembled that seen in the rat, with the cells concentrating at the superior-temporal margin of the retina. In the rabbit, TH-IR cells concentrated weakly in the visual streak, but at both ends of the streak the concentration of TH-IR cells extended farther peripherally than the concentration of ganglion cells. Overall, the distribution of TH-IR cells seems largely or (in the rabbit) partially independent of the distribution of ganglion cells. This independence raises questions of the development and function of this group of amacrine cells. PMID- 2893815 TI - Somatostatin-like immunoreactive material in the rabbit retina: immunohistochemical staining using monoclonal antibodies. AB - Two mouse monoclonal antibodies to somatostatin-14 were used with avidin-biotin peroxidase immunohistochemical technique to examine the rabbit retina. In agreement with a previous study using a polyclonal anti-serum, a sparse population (about 1,000 per retina) of neurons in the ganglion cell layer are immunoreactive for somatostatin; the vast majority of these cells are inferior to the myelinated fiber bundle. In addition, the monoclonal antibodies disclose a second neuronal population that forms a circumferential band of immunoreactive neurons around the extreme periphery of the retina. The cells in the body of the inferior retina have dendrites that ramify in the inner plexiform layer. Both the circumferential band of cells and the cells in the body of the inferior retina give off axonlike processes that run in the inner plexiform layer and do not enter the optic nerve. These long, straight varicose fibers form a meshwork that covers the entire retina. The superior retina, which contains only rare immunoreactive cell bodies, has a plexus of stained fibers comparable to that of the inferior retina. The circumferential band of cells is relatively resistant to the neurotoxin kainic acid, explaining a previously reported observation that this toxin depletes only about 50% of the content of somatostatin-like immunoreactivity from the rabbit retina. Moreover, the somatostatin immunoreactive neurons are not labeled by the intraocular injection of the fluorescent dye DAPI, which labels the cholinergic displaced amacrine cells of the rabbit retina. These observations imply that somatostatin-like immunoreactivity is localized to two populations of associational ganglion cells, neurons with cell bodies in the ganglion cell layer, the axons of which remain within the retina. PMID- 2893817 TI - Glycoconjugate boundaries during early postnatal development of the neostriatal mosaic. AB - The dispositions of galactosyl-containing glycoconjugates were studied during postnatal development of the caudate putamen in mice. The binding of the lectin peanut agglutinin, which has an affinity for galactosyl B-1,3 N acetylgalactosamine residues, was compared to acetylcholinesterase staining and tyrosine hydroxylase immunoreactivity in the immature and adult neostriatum. The binding of peanut agglutinin conjugated to horseradish peroxidase, in sections that were processed for peroxidase histochemistry, was extremely pronounced in the neostriatum through the first postnatal week and constituted ringlike or polygonally shaped structures, which, overall, produced a variegated mosaic. These structures consist of outer rims of dense lectin-associated reaction product surrounding lightly labeled centers. Lectin delineations of the neostriatal mosaic are no longer visible in the second postnatal week. When adjacent sections were processed for lectin binding or acetylcholinesterase histochemistry, the dense lectin binding sites represented borders of acetylcholinesterase-rich and -poor zones. The distribution of dense patches of tyrosine hydroxylase immunoreactive fibers and terminals also coincides with the acetylcholinesterase-rich zones during the same times, and thus the glycoconjugate-delineated boundaries can also be directly compared with the distribution of nigrostriatal dopaminergic projections. The findings presented here represent the first demonstration of a probe that recognizes apparent borders of neostriatal compartments during a limited period of development. They are consistent with previous observations made on transient glycoconjugate "hidden boundaries" during development of other central nervous system structures, including the somatosensory cortical barrel field, and thalamic and brainstem nuclei (Cooper and Steindler, '86a,b; Steindler and Cooper, in press). In those studies, glia were shown to be the major source of glycoconjugate associated patterns, and thus, glia and glycoconjugates that they synthesize during pattern formation events may be involved in the formation and stabilization of neurochemically distinct components of the neostriatal mosaic. PMID- 2893818 TI - Dohi memorial lecture. Cutaneous T cell lymphoma. PMID- 2893819 TI - Effect of two thymosin fraction 5 polypeptides on human peripheral blood lymphocytes. AB - Thymosin fraction 5 polypeptides beta 4 and alpha 1 were tested for their ability to affect certain immunological parameters of human peripheral blood lymphocytes (PBL). PBL were cultured with various concentrations of the peptides for 24 hours. Thymosin beta 4 was found to induce a significant decrease in the expression of the Fc alpha receptors of PBL, as well as in their ability to express antibody dependent cellular cytotoxic (ADCC) activity. In addition, this peptide had the ability to increase the percentage of T4 lymphocytes in normal and immunosuppressed donors and to decrease the percentage of T8 positive cells in normal donors. Finally, beta 4 peptide caused a small increase in the capacity of peripheral blood lymphocytes to form sheep red blood cell (SRBC) rosettes (ER). In parallel experiments thymosin alpha 1 was found inactive. The results presented here indicate that thymosin beta 4 may be used as an immunoregulatory molecule in patients with immunodeficiencies. PMID- 2893820 TI - Effects of dynorphin on the PHA-induced lymphocyte proliferation in vitro. AB - The effect of the opioid peptide dynorphin (DYN) on PHA-induced lymphocyte proliferation has been evaluated in the present study. A significant increase in PHA-induced lymphocyte activation was observed when DYN was added to cultures 48 hr after the mitogenic stimulation. This effect occurred at suboptimal (3.12 and 6.25 micrograms/ml) PHA concentrations and at DYN doses ranging from 10(-9) to 10(-12) M. Conversely, DYN did not affect the lymphocyte blastogenic process either when added before, or simultaneously or after intense PHA (12.5 micrograms/ml) stimulation. Naloxone preincubation did not modify the above described effects. Results suggest that DYN might play a role in neuroendocrine regulation of the lymphocyte blastogenic process. PMID- 2893821 TI - Selective T cell defects induced by dopamine administration in mice. AB - Dopamine administration in BALB/c mice depressed the overall delayed-type hypersensitivity reaction to sheep red blood cells, the mixed-lymphocyte culture responses, the generation of cytotoxic T cells, and the number of spleen T cell populations. Conversely, dopamine enhanced concanavalin A stimulation of spleen cells, and had no effect on stimulation by PHA, on total spleen and thymus cell number, and on distribution of thymus Ly-t1+ or Ly-t2+ cell subsets. These results indicate that dopamine produces selective T cell defects probably mediated by a direct peripheral action of the drug on subsets of T lymphocytes. PMID- 2893822 TI - Regulation of the CD2 alternate pathway of T cell activation by CD3. Evidence for heterologous desensitization. AB - Normal resting T cells were stimulated through the alternate CD2 pathway. A CD3 mAb VIT3 completely blocked their proliferative response. The time interval for 50% inhibition lasted for 24 h after the onset of CD2 stimulation. Mitogen activated cloned long term cultured T cells could also be stimulated via CD2. This proliferative response was again inhibitable by VIT3, indicating that CD3 regulates the CD2 pathway not only in resting cells, but also in lymphocytes actively involved in an Ir. T cells were further loaded with Quin2 and their free cytoplasmic Ca2+ levels were monitored in response to CD3 and CD2 stimulation. Antibodies directed against both surface R triggered a rapid elevation of Ca2+ levels. Both responses were abrogated when the cells had been treated overnight with VIT3. The free cytoplasmic Ca2+ levels of VIT3-pretreated cells, however, were not higher than those of control cells. These results point to a functional interaction between CD3 and CD2 possibly at the level of signal transducing proteins. Finally, cholera toxin was found to inhibit the Ca2+ response in Jurkat T cells. Both the CD3 and CD2 stimulation were sensitive to cholera toxin, indicating that a GTP-binding protein may be involved in signal transduction for both surface structures. PMID- 2893823 TI - Proliferation and production of IL-2 and B cell stimulatory factor 1/IL-4 in early fetal thymocytes by activation through Thy-1 and CD3. AB - To examine which cell surface molecules can operate as transducers of activation signals to early fetal thymocytes, we analyzed the ability of mAb to CD3 and Thy 1 to induce fetal thymocyte activation. Both proliferation and lymphokine secretion were used as measures of activation. We show that anti-CD3 antibodies induce activation of fetal thymocytes as early as day 13 of fetal thymus development, 2 days before CD3 can be detected by flow cytometry. In addition, an alternative activation signal can be delivered to fetal thymocytes through the Thy-1 molecule as early as it is expressed, i.e., day 13. Both CD3- and Thy-1 mediated activation of day 15 fetal thymocytes results in expansion of cells expressing a CD3-gamma delta receptor complex; no CD3-alpha beta receptor complex could be detected. IL-2 production induced by CD3- and Thy-1-induced activation of fetal thymocytes is evident at the 13th day of gestation. Finally, an additional lymphokine B cell stimulatory factor-1 (BSF-1)/IL-4 (so far known only to be produced by mature CD3- cells), is also produced by fetal thymocytes. The results demonstrate that at least two cell surface molecules, Thy-1 and CD3, can function as pathways of activation in fetal thymocytes, and that at least two lymphokines, IL-2 and BSF-1/IL-4, are produced upon activation. These findings may well reflect a role for the early appearance of CD3- cells in thymus ontogeny. PMID- 2893825 TI - Sequences of the VH and VL regions of murine monoclonal antibodies against 3 fucosyllactosamine. AB - Many mAb that bind the carbohydrate antigenic determinant 3-fucosyl-lactosamine (3-FL), Gal beta 1-4[Fuc alpha-3]GlcNAc-R have been raised in BALB/c mice, and we are studying the structure and regulation of these antibodies. In this report, we present the first information about their amino acid sequences and the Ig gene segments used to encode them. V regions of the H and L chains of three anti-3-FL antibodies, PMN6, PMN29, and PM81, were sequenced by a combination of mRNA and amino acid sequencing. The L chain sequences of PMN6 and PM81 antibodies indicate that their VK and JK regions are encoded by VK24B and JK1 germ-line genes, respectively. The nucleotide and amino acid sequences of the H chains suggest that the three anti-3-FL antibodies are encoded by the VH441 gene segment of the X24 VH family, and this conclusion was supported by Southern filter hybridization with VH441 and JH3-JH4 probes. PMN29 has at least 11 amino acid substitutions, which is an unusually large amount of somatic mutation for an IgM antibody. Previous analyses of BALB/c genomic libraries with VHX24 and VH441 probes make it unlikely that this VH family contains additional germ-line genes, but this possibility cannot be excluded. All three antibodies use the DQ52 and JH4 gene segments. The single VH and VL gene segments used to encode the anti-3-FL antibodies is in contrast to the multiple VH and VL segments used by antibodies against other carbohydrate Ag such as alpha 1-6 dextran and group A streptococcal carbohydrate. VH441 also encodes the VH regions of antibodies against galactan and levan (beta 2-6 fructosan). The similarities among VH segments of antibodies against 3-FL, levan, and galactan, and the striking differences in their CDR3 sequences, suggest that CDR3 plays an important role in the formation of the Ag binding site. The use of a single VH segment from the smallest VH gene family by antibodies against at least three different carbohydrate determinants is noteworthy. It raises the possibility that the amino acid sequence encoded by VH441 has some general structural features that make it particularly well adapted for binding to carbohydrate sequences. PMID- 2893824 TI - Molecular properties and regulation of mRNA expression for murine T cell replacing factor/IL-5. AB - We previously cloned cDNA for a T cell-replacing factor (TRF) that has been defined as a T cell-derived lymphokine that acts on activated B cells as a B cell growth and differentiation factor. Based on the diverse activities of rTRF on different target cells, we proposed that TRF be called IL-5. In this study, the molecular characteristics of TRF/IL-5 prepared by rDNA technology and TRF/IL-5 mRNA expression in various T cell lines and normal T cells have been studied. Specific immunoassay showed that rTRF/IL-5, which is transiently translated in vitro by rabbit reticulocyte lysate, has an apparent m.w. of 14,000. By contrast, active forms of rTRF/IL-5 translated in Xenopus oocytes has an apparent m.w. of 45,000 to 50,000 in the nonreducing condition and migrates to the m.w. of 25,000 to 30,000 under the reducing condition, indicating that active form of rTRF/IL-5 consists of dimer forms. The rTRF/IL-5 does not show detectable levels of IL-2, IL-3, and B-cell stimulatory factor 1 (IL-4) activities. Northern blot hybridization of poly (A)+ RNA from constitutively TRF-producing B151K12 T cell hybridoma revealed a single 1.7-kb band hybridizing to the cloned murine TRF/IL-5 cDNA. The expression of TRF/IL-5 mRNA in B151K12 was augmented by the stimulation with PMA plus calcium ionophore. In contrast, neither thymoma BW5147 nor IL-2 producing T cell hybridoma A55, both of which produced an undetectable level of TRF, expressed detectable levels of TRF/IL-5 mRNA. Stimulation of EL 4 and D9 cells with PMA and Con A, respectively, induced an increase in the levels of TRF/IL-5 mRNA expression accompanied by TRF/IL-5 production, whereas both cell lines did not show significant gene expression in the absence of the stimulation. In spleen cells from Mycobacterium tuberculosis-primed mice, significant expression of TRF/IL-5 mRNA was detected only when the cells were stimulated with relevant Ag, PPD. Normal spleen cells stimulated with Con A showed a significant, but approximately four-fold less expression of TRF/IL-5 mRNA. Molecular and functional properties of TRF/IL-5 will be discussed. PMID- 2893826 TI - Nonimmune binding of Ig to Clostridium perfringens. Preferential binding of IgM and aggregated IgG. AB - In an attempt to find a bacterial IgM receptor, a large number of bacterial strains of different species were screened for the ability to bind human IgM. Certain strains of the anaerobic bacterium Clostridium perfringens were found to bind a major fraction of polyclonal IgM. One bacterial strain showed a particularly high binding capacity and was studied in more detail. This strain is also able to bind a minor fraction of polyclonal IgA and IgG. Inhibition experiments indicate that the different Ig classes bind to one and the same R structure. The ability of the strain to bind polyclonal Ig is correlated to the number of subunits in the Ig. This correlation can most simply be explained by increasing avidity with increasing number of subunits. In agreement with this hypotheses, experiments with aggregated IgG show that binding ability increases with aggregate size. Experiments with Ig fragments indicate that the binding structure in Ig is located in the F(ab')2 region. The ability of this bacterial strain to bind a majority of IgM molecules as well as aggregated IgG is potentially useful in immunologic work and represents a new type of Ig binding to bacteria. PMID- 2893828 TI - A comparison of laboratory and clinical methods for diagnosing pertussis in an outbreak in a facility for the developmentally disabled. AB - During a pertussis outbreak in a facility for the developmentally disabled, culture- or direct fluorescent-antibody-confirmed cases were identified in 24 residents and 17 staff members; 38 (93%) were culture positive for Bordetella pertussis. An enzyme-linked immunosorbent assay (ELISA) was used to detect serum IgG and IgA to the filamentous hemagglutinin and lymphocytosis-promoting factor of B. pertussis. Using criteria from ELISA values, we identified an additional 83 residents and 28 staff members as seropositive. Among seropositive persons, antibody levels were elevated by the time of onset of respiratory symptoms and, in three of the four assays, remained elevated for 14 mo. In 44 seropositive persons tested within two weeks of onset of symptoms, 80% were culture positive, compared with 33% of 15 tested two to four weeks after onset (P = .003) and none of 15 tested more than four weeks after onset. The most specific (94%) clinical case definition identified only 41% of seropositive persons. Thus, ELISAs are important tools for individual diagnosis and epidemiological studies of pertussis. PMID- 2893827 TI - Molecular genotypes of the human T cell receptor gamma-chain. AB - New RFLP of the human TCR gamma-chain defined by a single restriction enzyme (PvuII) are described. They define three alleles and allow haplotype assignments within families. They occur at a high frequency within the population studied and are useful for studies on disease associations with the gamma-chain genes. The PvuII sites flank the C gamma 2 gene. A polymorphic site maps to an area 0.5 kb downstream of C gamma 2-exon III. The second RFLP appears to be the result of a 3 kb insertion giving rise to differences in the number of copies of exon II in the C gamma 2 gene. PMID- 2893829 TI - Yawning as a complication of electroconvulsive therapy and concurrent neuroleptic withdrawal. AB - Among the various reported neuropsychological effects of electroconvulsive therapy are amnesia, delirium, peripheral neuropathy, headaches, and seizures. A case history is presented that describes a previously unreported neurological sequela: the development of intractable yawning during a course of electroconvulsive therapy. Neuropathophysiological mechanisms possibly relating to this phenomenon are discussed. PMID- 2893831 TI - Quantitative characterization and spinal pathway mediating inhibition of spinal nociceptive transmission from the lateral reticular nucleus in the rat. AB - 1. The modulation of spinal nociceptive transmission from the lateral reticular nucleus (LRN) was characterized for 47 spinal dorsal horn neurons in pentobarbital-anesthetized, paralyzed rats. All 47 units studied had receptive fields confined to the glabrous skin of the plantar surface of the ipsilateral hind foot and responded to mechanical stimulation as well as noxious heating (50 degrees C). Rostral projections contained in the ventrolateral quadrant of the cervical spinal cord were demonstrated for 15 of the 47 units by antidromic invasion. Glutamate- and stimulation-produced descending inhibition, the spinal pathway, and tonic descending inhibition from the LRN were systematically examined. 2. Inhibition of unit responses to heating of the skin by electrical stimulation in the LRN varied with the intensity, pulse duration (100 or 400 microseconds), and frequency (25-100 Hz) of stimulation. Greater inhibition was produced at lower intensities of stimulation with the 400-microseconds pulse duration and a frequency of 100 Hz. The effects of stimulation on spontaneous activity and responses to heat were compared in 16 experiments; inhibition of spontaneous activity was intensity dependent and did not differ significantly in magnitude from stimulation-produced inhibition of responses to heating of the skin. 3. Tracking experiments established that stimulation in the ipsilateral and contralateral ventrolateral medulla reliably attenuated unit responses to noxious heating of the skin and that stimulation in the LRN produced maximal inhibition at a low intensity of stimulation. Descending inhibition was quantitatively characterized from sites within (n = 32) and outside (n = 30) the LRN. Both the extrapolated mean stimulation threshold for inhibition and mean intensity inhibiting unit responses to heat to 50% of control were significantly lower for sites in the LRN. 4. The responses of seven spinal units to graded noxious heating of the skin were studied; all exhibited linear monotonic stimulus response functions (SRFs) throughout the temperature range examined (42-50 degrees C). Electrical stimulation in the LRN significantly decreased the slope (42 +/- 4% of control) of the SRFs and increased the neuronal response threshold (2.0 +/- 0.7 degrees C). 5. S-glutamate (50 nmol, 0.5 microliter) was microinjected into stimulation sites within (n = 15) and distant from (n = 6) the LRN. Glutamate produced a transient (less than 7 min) but significant attenuation of neuronal responses to heat to 35 +/- 6% of control only when microinjected into the LRN.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2893830 TI - Electrophysiological evidence from glutamate microapplications for local excitatory circuits in the CA1 area of rat hippocampal slices. AB - 1. Evidence for local excitatory synaptic connections in CA1 of the rat hippocampus was obtained by recording excitatory postsynaptic potentials (EPSPs) intracellularly from pyramidal cells during local microapplications of glutamate. 2. Experiments were performed in hippocampal slices cut parallel to (transverse slice) or perpendicular to (longitudinal slice) alvear fibers. In normal solutions, glutamate microdrops (10-20 mM, 10-20 micron diam) applied in CA1 within 400 micron of recorded cells sometimes increased the frequency of inhibitory postsynaptic potentials for 5-10 s in both transverse and longitudinal slices. Increases in EPSP frequency were also occasionally observed, but only in transverse slices. Tetrodotoxin (1 microgram/ml) blocked glutamate-induced increases in PSP frequency, thus indicating that they were not caused by subthreshold effects on presynaptic terminals. Increases in PSP frequency were interpreted to result from glutamate activation of hippocampal neurons with inhibitory and excitatory connections to recorded neurons. 3. In both slice orientations, local excitatory circuits were studied in more isolated conditions by surgically separating CA1 from CA3 (transverse slices) and by blocking GABAergic inhibitory synapses with picrotoxin (5-10 microM). Microdrops were systematically applied at 200 and 400 micron on each side of the recording site. Significant glutamate-induced increases in EPSP frequency were observed in neurons from both slice orientations to microdrops in at least one of the locations. This provided evidence that excitatory synapses are present in both transverse and longitudinal slices. 4. Substantial increases in EPSP frequency only occurred in neurons from longitudinal slices when glutamate was microapplied 200 micron or less from the recording site. In transverse slices, however, large increases in EPSP frequency were observed to glutamate microapplications at 200 or 400 micron. These data suggest that CA1 local excitatory connections project for longer distances in the transverse than in the longitudinal plane of section. 5. Increases in EPSP frequency, averaged across cells, did not differ significantly in the four microapplication sites in either transverse or longitudinal slices. Thus local excitation in CA1 does not appear to be asymmetrically arranged in the way suggested for CA3. 6. The densities of local excitatory circuits in CA1 versus CA3 were studied by quantitatively comparing glutamate-induced increases in EPSP frequency.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2893832 TI - Characteristics of local excitatory circuits studied with glutamate microapplication in the CA3 area of rat hippocampal slices. AB - 1. Local neuronal circuits in CA3 of hippocampal slices were studied by recording excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) intracellularly during glutamate microapplication in CA3. Control experiments validated this approach by providing evidence that glutamate microdrops stimulated neurons but not axons-of-passage or axon terminals in CA3. 2. Glutamate microdrops (10-20 mM, 10-20 microns diam) increased the firing frequency of extracellularly recorded dentate granule cells for 5-10 s when applied to their somata but not when applied to their mossy fiber axons and terminals in the hilus and in CA3. 3. Glutamate microapplications to granule cell somata, but not to mossy fiber axons, also increased the frequency of intracellularly recorded EPSPs in CA3 pyramidal cells for 5-10 s. This provided a second line of evidence that glutamate did not cause firing in mossy fiber axons synapsing in CA3. 4. In slices where the CA3 region was surgically separated from the dentate gyrus and CA2, glutamate microdrops placed in the CA3 stratum pyramidale within 400 microns of intracellularly recorded pyramidal cells increased the frequency of EPSPs and IPSPs. Tetrodotoxin (1 microgram/ml) blocked these increases in PSP frequency, indicating that they did not result from glutamate-induced depolarization and associated transmitter release from presynaptic terminals. Increases in PSP frequency were interpreted to reflect glutamate activations of CA3 neurons with local synaptic connections to recorded cells. 5. Low concentrations of picrotoxin (PTX, 5-10 microM) blocked glutamate induced increases in IPSP frequency and often revealed increases in EPSP frequency where they were not previously observed. This suggests that recurrent inhibitory circuits normally mask or block transmission through recurrent excitatory pathways in CA3. 6. In five experiments following PTX treatment (7.5 10 microM), large and prolonged (up to 2 min) increases in EPSP frequency were observed in CA3 pyramidal cells to glutamate microapplications in CA3. Rhythmic epileptiform bursts eventually occurred in two of these cases, suggesting that the protracted increases in EPSP frequency represent a form of reverberating excitation during a transition from normal to epileptic states. 7. Sixteen CA3 pyramidal cells were recorded in PTX (5-10 microM) during glutamate microapplications at 200 and 400 microns on each side of the recording site. The most consistent glutamate-induced increases in EPSP frequency occurred to microapplications 200 microns from recording sites on the hilar side.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2893833 TI - Essential fatty acid status in southern Thai preschool children. AB - Essential fatty acid (EFA) status was assessed in 15 Southern Thai preschool children. The mean (+/- SD) serum linoleate (18:2 n-6), arachidonate (20:4 n-6), linolenate (18:3 n-3), eicosapentaenoate (20:5 n-3), and docosahexaenoate (22:6 n 3) percentages in the preschool children were 21.7 +/- 4.0, 6.0 +/- 1.2, 0.4 +/- 0.1, 1.2 +/- 0.8, and 4.4 +/- 1.3, respectively. Since EFA composition of total serum lipids in healthy children are not available and age and sex do not largely influence these parameters, the results of the preschool children were compared with those of 10 healthy Bangkok adults. The corresponding figures of the aforementioned fatty acids in adults were 34.9 +/- 8.5, 4.6 +/- 1.5, 0.8 +/- 0.4, 0.5 +/- 0.4, and 1.6 +/- 0.8, respectively. The data indicate linoleate and linolenate depletion in the preschool children. This was due to their low fat intake and lack of consumption of vegetable oil rich in linoleic and linolenic acids. Their high serum arachidonate percentage was probably due to the increased conversion of 18:2 n-6 to 20:4 n-6 in the presence of linolenate depletion. The significantly higher serum 20:5 n-3 and 22:6 n-3 percentages in the preschool children should be due to direct consumption of these two n-3 fatty acids from fish intake. PMID- 2893835 TI - [Synthetic studies on surugatoxin, neosurugatoxin and prosurugatoxin]. PMID- 2893834 TI - Interactions of befunolol, a beta-adrenergic partial agonist, and its derivatives with high and low affinity sites in beta-adrenoceptors. AB - Modes of action of befunolol and its derivatives were tested in guinea pig isolated taenia caecum. The pA2-values of BFE-60 (befunolol), -61 and -69 against isoprenaline, which measures interactions with the high affinity sites on beta adrenoceptors, were significantly larger than their pD2-values, which were equal to their pA2-values against carteolol. Carteolol is a beta-adrenergic partial agonist with higher intrinsic activity, to which the response results from interaction with low affinity sites. These results suggest that BFE-60, -61 and 69 discriminate the high and low affinity sites on beta-adrenoceptors. The pA2 values of BFE-37, -41, -47 and -72 against isoprenaline were, however, equal to their pD2-values and pA2-values against carteolol. These drugs seem to have little or no ability to discriminate between the high and low affinity sites. BFE 55 antagonized isoprenaline but not carteolol suggesting that BFE-55 interacted with only the high affinity sites. PMID- 2893836 TI - [Elucidation of toxins and their origin in the Japanese ivory shell, Babylonia japonica]. PMID- 2893838 TI - Perinatal, not adult, hypothyroidism suppresses dopaminergic axon sprouting in the deafferented olfactory tubercle of adult rat. AB - We reported recently that chronic thyroid deficiency in rat, beginning in utero and terminating after maturity, suppresses lesion-induced central catecholaminergic axon sprouting in the adult brain [Gottesfeld et al, 1985]. The present work was undertaken to define the critical period of hypothyroidism on subsequent neuronal sprouting. Thyroid hormones deficiency was induced in rats by methimazole during (a) gestational days 8-21 (20 mg/kg/day in the drinking water); (b) postnatal days 1-15 (0.2 or 0.4 mg/pup/day; i.p.), or (c) in the mature animal for 4 weeks (20 mg/kg/day in the drinking water). The olfactory tubercles (OTs) were used as a model to study sprouting of dopaminergic (DA) nerve terminals, elicited by olfactory bulbectomy. Animals in each group received lesions or sham operations as adults, and sacrificed 3 weeks after the operation. Thus, for each of the above treatments four subgroups were formed: (a) euthyroid/sham-operation, (b) euthyroid/lesion, (c) hypothyroid/sham-operation, and (d) hypothyroid/lesion. Sprouting of DA axon terminals in the OTs was identified by biochemical assays and quantitative immunofluorescent microscopy, using tyrosine hydroxylase (TH) as a marker. Serum thyroxine levels served as an index of the thyroid status. The results demonstrate that lesion-induced sprouting of DA axon terminals in OTs of adult rats is suppressed by hypothyroidism induced prenatally or during the early postnatal period, but not after maturity. Thus, there is a perinatal critical period during which altered thyroid function exerts long-term effects on neuronal plasticity. PMID- 2893837 TI - Quisqualate-sensitive, chloride-dependent transport of glutamate into rat brain synaptosomes. AB - A chloride-dependent transport process for glutamate has been identified in partially purified rat brain synaptosomes. This process shares many characteristics with the chloride-dependent sequestration process for glutamate in brain sonicates, which was previously thought to represent a quisqualate receptor, such as sensitivity to specific inhibitors and regulation by anions. Increasing the concentrations of chloride led to an increase in the apparent Vmax without affecting the KT. Synaptosomes preincubated with [3H]-L-glutamate exhibit an efflux of the radiolabel, which was stimulated by a substrate for the carrier in the incubating medium, indicating the bidirectional nature of the transport. The chloride-dependent transfer process is restricted to the brain, and regional and developmental profiles clearly distinguish it from the sodium-dependent high affinity uptake process for glutamate. Nevertheless, the effects of excitotoxic lesions strongly suggest a neuronal localization of the chloride-dependent transport. PMID- 2893839 TI - Pharmacological modulation of postprandial colonic motor activity in the pony. AB - The contractile activity of the equine large intestine exhibited a biphasic response to feeding: enhancement of migrating complexes passing along the colon and an increase of 50% in cyclic variations in smooth muscle at intervals of 20 min on the left ventral colon for a period of 5 to 7 h postfeeding. The cholinergic agonist, bethanechol (50 micrograms/kg subcutaneously), induced both the migrating complexes and the cyclic variations at intervals of 10-15 min. In contrast, the intra-arterial infusion of PGF2 alpha (3 micrograms/kg/min) increased the contractile activity during infusion, but without inducing distinct patterns of activity. Atropine but not indomethacin or flunixin pre-treatment prevented the effects of postprandial, cholinergic and PGF2 alpha stimulation of colonic motility, suggesting that the gastrocolonic reflex involved mainly cholinergic stimulation of the caecum and replicated colon, including the prostaglandin F2 alpha excitatory effects. PMID- 2893840 TI - Colonic alpha 2-adrenoceptor-mediated responses in the pony. AB - The motor responses of the caecum and colon to stimulation of alpha 2 adrenoceptors by xylazine and detomidine at the recommended dose levels of 0.6 and 0.1 mg/kg were investigated in three ponies. The motor changes of the left ventral colon induced by continuous intra-arterial infusion of a prostaglandin (PGF2 alpha) were used to assess the relative inhibitory effects of xylazine and detomidine in a colic model. The administration of alpha 2-agonists inhibited the spiking activity on the whole of the large intestine for 20-30 min (xylazine) or 2-3 h (detomidine). However, the detomidine-induced inhibition was preceded by a short period of increased smooth muscle basal tone as indicated by strain-gauge force transducer measurements. This pattern of activity was neither reversed nor prevented by the administration of tolazoline (10 micrograms/kg/min) intra arterially. In contrast, inhibition of the colonic phasic and tonic motor activity by alpha 2-adrenoceptor stimulation was reversed competitively by tolazoline. The intra-arterial infusion of prostaglandin F2 alpha (10 micrograms/kg/min) induced prolonged and sustained spiking activity that might be related to signs of mild colic. Detomidine, and to a lesser extent xylazine, relaxed the whole of the large intestine and this was accompanied by alleviation of the signs of visceral pain. PMID- 2893841 TI - Sedative action of the alpha 2-agonist medetomidine in cats. AB - Medetomidine, a novel alpha 2-agonist drug intended for small animal sedation, was injected intramuscularly at dose rates of 0.02, 0.06 and 0.18 mg/kg. Xylazine (3.0 mg/kg) and saline were used for comparison. The five treatments were tested in a Latin square design in five cats. Treatments differed significantly in three way analysis of variance, medetomidine inducing an increase in drowsiness with a corresponding decrease in both aroused waking and sleep determined by polygraphical criteria. The duration of effect was dose-dependent. The effect of 0.18 mg/kg medetomidine was comparable to 3.0 mg/kg of xylazine. The drugs also induced bradycardia. PMID- 2893842 TI - Regional noradrenergic and cholinergic neurochemistry in the rat urinary bladder: effects of age. AB - Neurochemistry of the base and body of the rat urinary bladder was compared for both adrenergic and cholinergic parameters using Fischer 344 rats. In bladder base and body, respectively, the concentration (pmol./mg. wet weight) of norepinephrine was 23.4 and 2.16, of acetylcholine was 26.7 and 18.3, and of choline was 96.7 and 199. The activity (nmol./mg. protein/hour) of tyrosine hydroxylase was 422 and less than 50, of monoamine oxidase was 80.6 and 126, of choline acetyltransferase was 17.4 and 11.5, and of acetylcholinesterase (nmol./mg. wet weight/hour) was 485 and 165. Treatment with alpha-methyl-p tyrosine did not alter norepinephrine concentration in bladder base but decreased it by 27% in bladder body. Studies were also done to determine whether age related changes exist in the adrenergic and cholinergic neurochemistry of the rat urinary bladder. Bladders from rats of 6-7, 15-17, and 22-24 mo. of age were examined. The only age-related differences noted were a progressive decrease in level of monoamine oxidase activity in both bladder regions and an increase in bladder base norepinephrine concentration from 6-7 to 15-17 mo. followed by a decrease at 22-24 mo. Overall, the results show marked regional variations in bladder neurochemistry which remain remarkably stable as the animals grow old. PMID- 2893844 TI - Leads from the MMWR. Korean hemorrhagic fever. PMID- 2893843 TI - Effect of bethanechol on glycolysis and high energy phosphate metabolism of the rabbit urinary bladder. AB - The urinary bladder, similar to other smooth muscles, utilizes glucose as one of its primary sources of metabolic energy. We have studied the effect of bethanechol on both glycolysis and high energy phosphate metabolism. The results can be summarized as follows: bethanechol administration in vitro stimulates a 30% decrease in intracellular glycogen, a 100% increase in lactic acid production, and an 80% increase in CO2 generation. Although there was a rapid and sustained decrease in the intracellular concentration of creatine phosphate, there was only a minor decrease in the intracellular concentration of ATP. There were no changes in adenine uptake or de novo ATP synthesis. PMID- 2893845 TI - The complications of 'ecstasy' (MDMA) PMID- 2893847 TI - [HTLV-I associated myelopathy (HAM) in Fukushima Prefecture]. PMID- 2893846 TI - [Proliferation of both helper/inducer and suppressor/cytotoxic cells in a case of adult T-cell leukemia]. PMID- 2893848 TI - [Analysis of anti-HIV antibody and the production of monoclonal antibodies]. PMID- 2893849 TI - [Antibodies to adult T-cell leukemia associated antigen (ATLA) in various diseases in an ATL non-endemic area, especially in relation to blood transfusion]. PMID- 2893850 TI - Diagnosis of Duchenne and Becker muscular dystrophies by DNA polymorphism. PMID- 2893851 TI - [Gallium scintigraphy in patients with adult T-cell leukemia-lymphoma]. PMID- 2893852 TI - Pharmacological and electrophysiological discrimination of contractile responses to selective alpha 1- and alpha 2-adrenoceptor agonists in rat tail artery. AB - Pharmacological and electrophysiological properties of postsynaptic alpha adrenoceptor subtypes in rat tail artery were compared using selective alpha 1- and alpha 2-adrenoceptor agonists. Five alpha-adrenoceptor agonists contracted the tail artery with the following order of maximal effects: norepinephrine (alpha 1 and alpha 2) greater than methoxamine (alpha 1) = phenylephrine (alpha 1) much greater than clonidine (alpha 2) greater than UK-14,304 (alpha 2). Phenoxybenzamine greatly diminished contractions induced by methoxamine and phenylephrine, but had little effect on responses to UK-14,304. Idazoxan antagonized more potently against UK-14,304 than against methoxamine. These results suggest the heterogeneity of postsynaptic alpha-adrenoceptors in the rat tail artery. Furthermore, responses to methoxamine and phenylephrine 1) had faster onsets and 2) were more resistant to Ca2+ entry blockers, nicardipine and diltiazem, and a promotor, Bay K 8644, or decreasing of extracellular Ca2+ and 3) were more sensitive to a calmodulin antagonist, W-7, than the responses to UK 14,304 and clonidine. Both methoxamine and UK-14,304 depolarized the membrane but methoxamine produced stronger depolarization than UK-14,304. Therefore, the high sensitivity of alpha 2-adrenoceptor agonists-induced responses to Ca2+ entry blockers and promotors cannot be accounted for solely by membrane depolarization. These results may indicate the differences in the Ca2+ movement for the contractions produced by alpha 1- and alpha 2-adrenoceptor agonists. PMID- 2893853 TI - Inhibitory effect of somatostatin on gastric acid secretion in rats. AB - Effects of somatostatin on parasympathetically induced increases in gastric acid secretion and mucosal blood flow (MBF) were studied in anesthetized rats with a gastric fistula. Intravenous infusion of small doses of somatostatin (0.1-0.5 microgram/kg/min) dose-dependently inhibited the increases in the vagally stimulated gastric acid secretion. Larger doses of somatostatin (0.5-2.5 micrograms/kg/min) also dose-dependently inhibited the bethanechol-induced gastric acid secretion. The dose of somatostatin required to inhibit the gastric acid secretion by about 50% of the preinfused control values was 0.25 microgram/kg/min for vagally stimulated acid secretion and 2.5 micrograms/kg/min for bethanechol-induced acid secretion. Thus, the inhibitory potency of somatostatin on the vagally stimulated gastric acid secretion was about 10-fold higher than that on bethanechol-induced acid secretion. Somatostatin had no effect on the increase in gastric MBF during vagus nerve stimulation or bethanechol infusion. Pretreatment with indomethacin or phentolamine had no effect on the inhibitory effect of somatostatin on the increase in gastric acid secretion during vagus nerve stimulation or bethanechol infusion. These results suggest that somatostatin exerts an inhibitory effect on gastric acid secretion by acting on the parasympathetic neurons in the gastric wall more than on the structures peripheral to the parasympathetic nerve terminals, and it reduces parasympathetically stimulated gastric acid secretion in rats. This inhibitory effect of somatostatin on the gastric acid secretion is independent of the changes in the gastric MBF and probably not related to prostaglandin-involved or alpha adrenoceptor-mediated mechanisms. PMID- 2893854 TI - Effects of beta-lactam antibiotics and N-methyltetrazolethiol on the alcohol metabolizing system in rats. AB - The disulfiram-like effect of various beta-lactam antibiotics containing N methyltetrazolethiol (NMTT) on the alcohol-metabolizing system was studied using rats. Their administration caused decreased activities in low Km aldehyde dehydrogenase (ALDH) and acetaldehyde oxidation in the liver, with marked depression from several hours to 2 days after the treatment. Blood acetaldehyde level increased markedly when ethanol was administered 18-24 hr after pretreatment with antibiotics. A similar time course change in the effect was obtained when disulfiram was administered. The following results obtained in the present study indicate that the disulfiram-like effect associated with these antibiotics was not mediated by the whole molecular structures of these drugs: Firstly, the antibiotics were eliminated rapidly from the plasma and liver, and the disulfiram-like effect was followed by a disappearance of the drugs. Secondly, the concentration of antibiotics required to inhibit mitochondrial low Km ALDH activity in vitro was very high compared with their liver concentration. Thirdly, rapid onset of disulfiram-like effects occurred after administration of NMTT itself, and a pronounced elevation of blood acetaldehyde level was observed when ethanol was administered 3-5 hr after the NMTT injection. Fourthly, almost the same amounts of NMTT were released in the body after the intravenous administration of various NMTT-containing antibiotics, as judged by the urinary excretion. These results suggest that the disulfiram-like effect of beta-lactam antibiotics is mediated by NMTT released from them. PMID- 2893855 TI - Effects of bunitrolol on adrenergic and serotonergic receptors. AB - To assess the importance of anti-adrenergic and anti-serotonergic activities of bunitrolol for its efficacy as an antihypertensive and antianginal agent, effects of this substance on the binding of adrenergic and serotonergic agents to the respective receptors of the rat brain, rat heart, dog brain, and/or dog aorta were examined using the radioligand binding assay methods. In addition, the pA2 values of bunitrolol as an antagonist against the positive chronotropic and inotropic actions (beta 1-adrenoceptor) of isoproterenol were also determined by pharmacological methods using the isolated guinea pig atria. To assess the specificity, pA2 values were also obtained in the isolated trachea (beta 2 adrenoceptor) using isoproterenol as an agonist and in the isolated aorta from the guinea pig and the rat using phenylephrine as an agonist (alpha 1 adrenoceptor). A strong inhibition by bunitrolol of 3H-dihydroalprenolol (3H-DHA) binding to beta-adrenoceptors was observed, while the inhibition of 3H-prazosin binding to alpha 1-adrenoceptors, 3H-serotonin binding to 5HT1-receptors. 3H-p aminoclonidine binding to alpha 2-adrenoceptors, and 3H-ketanserin binding to 5HT2-receptors were found to be very weak. The rank order of antagonistic potencies of bunitrolol against the adrenergic receptors as assessed with pA2 values were beta 1 greater than beta 2 much greater than alpha 1. From these two different types of experiments, it is clear that the antihypertensive and antianginal effects of bunitrolol are mainly due to its beta-blocking actions, with the alpha 1-blocking action of this drug playing a minor role. PMID- 2893856 TI - Effects of methamphetamine on the twitch response in the rat isolated vas deferens. AB - The effect of methamphetamine, an indirectly acting sympathomimetic amine, on presynaptic adrenergic regulation in isolated rat vas deferens was studied by comparing it with those of tyramine, cocaine and clonidine. These drugs markedly attenuated the twitch response to electrical field stimulation in a concentration dependent manner. The relative order of potency for the drugs was: clonidine (10( 10)-3 x 10(-8) M) greater than methamphetamine (10(-8)-3 x 10(-6) M) greater than tyramine (10(-7)-10(-4) M) greater than cocaine (10(-6)-3 x 10(-5) M). Only tyramine (3 x 10(-6)-10(-4) M) elicited a concentration-dependent contractile response, which was abolished by prazosin (10(-6) M) and the reserpinization. The twitch inhibitory effect of these drugs was antagonized by yohimbine (10(-8)-10( 6) M). Both the methamphetamine- and tyramine-induced twitch inhibition were partially (about 50%) attenuated by chronic reserpinization (3 mg/kg, s.c., twice) in combination with alpha-methyl-p-tyrosine (200 mg/kg, s.c., twice), while the clonidine-induced inhibition was not affected by this application at all, and the cocaine-induced twitch inhibition was abolished by the reserpinization. Both the clonidine- and tyramine-induced twitch inhibition were not affected by pretreatment with cocaine (10(-5) M) in combination with estradiol (4 x 10(-5) M), whereas the effect of methamphetamine was slightly attenuated. These results suggest that methamphetamine as well as tyramine and cocaine indirectly activates presynaptic alpha-2 adrenoceptors via norepinephrine released from adrenergic nerves to inhibit the twitch response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893857 TI - Effect of tritoqualine on the proliferation of interleukin-3 dependent cell line and sensitive cells. AB - In this paper, the effect of tritoqualine (TRQ) on the proliferation of interleukin (IL) sensitive cells was investigated. TRQ inhibited the proliferation of FDCp-2 (IL-3 dependent cell line), CTLL-2 (IL-2 dependent cell line) and bone marrow cells (BMC) stimulated by IL, giving an ID50 of about 3 microM equally in the three systems. However, a ten times higher concentration of TRQ was required to inhibit the tumor cell proliferation. TRQ did not affect the unstimulated bone marrow cells. Accordingly, it is suggested that TRQ may show its anti-allergic effect, at least partially, by interfering with the proliferation/differentiation to mast cell and basophils of multi-functional hemato-poietic cells stimulated by IL-3. PMID- 2893859 TI - [Hemodynamic effects of beta-adrenoblock by obsidan in clinostatics and orthostatics]. PMID- 2893858 TI - Amebic liver abscess in a European patient: zymodeme classification of Entamoeba histolytica. AB - This is a case report of a 36-year-old patient who developed an amebic liver abscess after a stay in the Sudan. He was first misdiagnosed as having pneumonia of the right lower lobe. Following establishment of the correct diagnosis, the patient recovered fully after metronidazole treatment. The fecal culture in Robinson's medium yielded extensive growth of Entamoeba histolytica. Electrophoretic characterization proved it to be a zymodeme XIX, which is one of the zymodemes associated with pathogenicity in the host. This first report of a zymodeme classification of E. histolytica in Germany should initiate further epidemiological studies. PMID- 2893860 TI - Electrocoating carbon fiber microelectrodes with Nafion improves selectivity for electroactive neurotransmitters. AB - A method which improves carbon fiber microelectrode selectivity for cationic amines by electrocoating the fiber with a thin film of the ionic polymer, Nafion, is described. The selectivity and response speed of these electrodes for the detection of electroactive cationic and anionic species found in brain extracellular fluid was evaluated using differential pulse voltammetry and chronoamperometry and compared to uncoated fibers. Carbon fiber microelectrodes electrocoated with Nafion are highly sensitive to cationic amines such as dopamine and serotonin and have minimal sensitivity to anions such as ascorbic acid and uric acid at physiological concentrations. PMID- 2893861 TI - HPLC analysis of putative amino acid neurotransmitters released from primary cerebellar cultures. AB - An HPLC method is described that measures amino acids (putative neurotransmitters and/or neuromodulators) released from primary, dissociated cerebellar cells maintained in monolayer culture. Precolumn derivatization with phenylisothiocyanate, followed by reverse phase chromatography with UV detection was used to quantitate the phenylcarbamyl amino acid derivatives in a chemically defined medium. Quantitation was linear, reproducible and sensitive to one picomole. This method is useful for the measurement of putative neurotransmitters GABA, glutamate, aspartate, taurine and adenosine, and can easily be modified to analyze other amino acids in physiological samples. PMID- 2893862 TI - Gene rearrangements of T cell receptor beta and gamma chains in HTLV-I infected primary neoplastic T cells. AB - Rearrangements of T cell receptor beta and gamma chain (T beta and T gamma) genes were analyzed by Southern blot method in samples from 30 patients with adult T cell leukemia (ATL) and 17 patients with non-ATL T cell neoplasms. The DNA probes used were the constant and joining region of T beta gene and the joining region of T gamma gene. Rearranged bands of T beta gene on one or both allelic chromosomes were detected in all neoplastic T cells, even those of smoldering ATL, in which only a small percentage of peripheral blood T cells were detected as leukemic. T gamma gene was rearranged in the cells of all but one patient, the exception being one ATL patient. In order to test whether any given variable region (V) of T beta gene was expressed in ATL cells, two functionally rearranged V beta sequences of ATL were compared with a V beta sequence from T cells acute lymphoblastic leukemia cells. No significant homologies were noted among the three deduced gene product amino acid sequences, confirming that T beta molecules of ATL cells contained no specific structures in common. The observed heterogeneity of T beta and T gamma gene rearrangements in ATL cells further supported these findings. PMID- 2893863 TI - In vitro effects of 4-hydroxyperoxycyclophosphamide on human immunoregulatory T subset function. AB - Treatment of T cells in vitro with low concentrations of 4 hydroperoxycyclophosphamide (4-HC) is known to result in immunopotentiation of both T and B cell effector function in a manner analogous to that of cyclophosphamide administered in vivo. A previous study demonstrated that augmentation of polyclonal immunoglobulin secretion occurs following pretreatment of autologous collaborating T cells with low concentrations of 4-HC as a result of blockade of suppressor effector induction from suppressor precursor, both of which share the identical T4+,8-phenotype. The present study was undertaken to examine the effects of 4-HC on regulatory T-T interactions in mixed lymphocyte culture (MLC) responses and for allospecific cytotoxic T lymphocyte (CTL) responses. Induction of CTL and MLC proliferation were found to be sensitive to as little as 40 microM 4-HC, whereas CTL effector function was resistant to greater than or equal to 80 microM. CTL effectors were restricted to the T4-,8+ subset and the cells showing sensitivity to low and intermediate 4-HC concentrations were found to be T4+,8-. Secondary MLC and CTL responses displayed a similar 4-HC concentration-dependent inhibition following drug treatment of the T4+ T subset which could only be detected at suboptimal responder to stimulator ratios. This suggests that the mechanisms of CTL induction by a T4+ inducer cell in primary and secondary MLC responses and the sensitivity of induction of 4-HC are qualitatively similar. Pretreatment of T cells with less than or equal to 20 microM 4-HC for one hour prior to Con A activation totally blocked suppressor effector induction both for MLC and CTL function. In contrast, treatment with 80 microM 4-HC following Con A induction was without effect on differentiated T suppressor effector activity. Studies utilizing monoclonal antibody/complement depletion and panning techniques demonstrated that the suppressor precursor and differentiated suppressors for T effector function were restricted to the T4+,8 subset. These results support the hypothesis that regulatory inducer T cell function is significantly more sensitive to the inhibitory effects of low to intermediate concentrations of 4-HC than either the suppressor-cytotoxic precursors themselves or suppressor/cytotoxic effectors. Con A inducible suppressor cell precursor induction (mediated by the T4+,8-subset) demonstrated the greatest sensitivity to 4-HC (less than or equal to 20 microM) followed by inducers of primary and secondary CTL (40-60 microM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2893864 TI - Randomised trial of alternative formulations of oral poliovaccine in Brazil. AB - In February to July, 1986, an outbreak of type 3 poliomyelitis occurred in north east Brazil that was linked to type-specific failure of trivalent oral polio vaccine (TOPV). To see if alternative vaccines would improve seroconversion to type 3, 441 children less than 5 years of age who had previously received no or up to four doses of TOPV were randomly assigned to receive one dose of standard TOPV (1,000,000, 100,000, and 300,000 median tissue culture infection doses [TCID50] of types 1, 2, and 3, respectively); a new formulation of TOPV containing twice the dosage of type 3 (600,000 TCID50); or a monovalent vaccine containing 300,000 TCID50 of type 3. While rates of seroconversion to types 1 or 2 were equivalent following vaccination with either formulation of TOPV, children who received the new formulation were 2.7 times more likely to seroconvert to type 3. Similar differences for type 3 were observed when monovalent vaccine was compared with standard TOPV, though both groups had received the same dose of type 3 antigen. The low rate of seroconversion to type 3 in the standard TOPV group was associated with a higher rate of reinfection with type 2, which also appeared to interfere to some extent with seroconversion to type 1. These findings extend earlier observations that interference from Sabin type 2 virus may be an important contributory cause of type-specific TOPV failure, and suggest that interference can be overcome with alterations in the formulation. PMID- 2893865 TI - Placebo-controlled trial of intravenous penicillin for severe and late leptospirosis. AB - The effect of a 7-day course of intravenous penicillin (6 million units/day) on severe, advanced leptospirosis was examined in a randomised, placebo-controlled, double-blind trial involving 42 patients. Every measurable aspect of the disease was favourably affected by penicillin. Fever lasted more than twice as long in the placebo group (11.6 [SD 8.34] days vs 4.7 [4.19] days, p less than 0.005), and by the fourth day after starting penicillin more than half the treatment group, but only 1 of 19 in the placebo group, were afebrile (p less than 0.005). Creatinine rises persisted more than thrice as long in the patients receiving only placebo (8.3 [8.46] days vs 2.7 [1.90] days; p less than 0.01). Penicillin also shortened the hospital stay and prevented leptospiruria. Intravenous penicillin should be given to patients with severe leptospirosis, even if therapy can be begun only late in the course of their disease. PMID- 2893866 TI - Successful treatment of homozygous protein C deficiency by hepatic transplantation. AB - A child with homozygous protein C deficiency was treated at age 20 months by orthotopic hepatic transplantation. Postoperatively there was complete reconstitution of protein C activity and resolution of the thrombotic condition. PMID- 2893867 TI - Postoperative positive nitrogen balance with intravenous hyponutrition and growth hormone. AB - 11 patients having major gastrointestinal surgery were allocated at random to receive either biosynthetic human growth hormone (BSHGH) 0.1 mg/kg or placebo daily for the first 7 postoperative days. All patients received the same intravenous feeding regimen, which contained 2.09 MJ glucose, 1.88 MJ fat, and 7 g N daily. Patients receiving BSHGH were in positive nitrogen balance throughout the study (mean 1.8 [SEM 0.4] g N/day) and those receiving placebo were in negative nitrogen balance (mean -0.9 [0.7] g N/day). Resting energy expenditure progressively increased in the patients receiving BSHGH (115.7% [14.8] on day 7) but remained unchanged in patients receiving placebo (99.35% [1.4]). Fat oxidation was nearly three times higher in the patients on BSHGH (4.09 [0.38] MJ/day) than in controls (1.38 [0.50]). Carbohydrate oxidation remained about the same in both groups. Whole-body protein turnover, synthesis, and breakdown were increased in the patients receiving growth hormone. PMID- 2893868 TI - Tuberculous meningitis due to BCG in two previously healthy children. AB - Tuberculous meningitis with favourable outcome has been observed in two immunocompetent previously healthy children. The mycobacteria isolated from the cerebrospinal fluid of both patients proved to be Mycobacterium bovis BCG. The patients had been inoculated with BCG, one 5 and the other 6 months before onset of the disease. PMID- 2893870 TI - Cough and wheeze in asthma: are they interdependent? PMID- 2893871 TI - Antenatal ionising radiation and cancer. PMID- 2893869 TI - Correlation of clinical phenotype to genotype in haemoglobin H disease. AB - Clinical assessment, haematological studies, and globin gene mapping were performed in 21 Greek subjects with haemoglobin H disease. Clinical phenotypes ranged from mild, and virtually asymptomatic, to severe cases requiring transfusion. The severe clinical phenotype was exclusively associated with non deletion genotypes, whereas the mild and intermediate phenotypes occurred with deletion genotypes. Patients with non-deletion genotypes had higher levels of Hb H. For deletion genotypes of haemoglobin H disease, the value of antenatal diagnosis is questionable. In non-deletion genotypes, antenatal diagnosis should be considered, because of the more severe clinical course observed in these patients. PMID- 2893872 TI - Propylthiouracil and alcoholic liver disease. PMID- 2893874 TI - Acquired vitamin D deficiency and hyperparathyroidism. PMID- 2893873 TI - Another audit. PMID- 2893875 TI - Predicaments of hysteria. PMID- 2893876 TI - Could an endogenous benzodiazepine ligand contribute to hepatic encephalopathy? AB - High affinity recognition sites for benzodiazepines are part of the gamma aminobutyric acid (GABA) supramolecular complex on the plasma membrane of neurons in the mammalian brain. Synthetic agonist benzodiazepines promote GABA-ergic neurotransmission, and hence the hypnotic and anxiolytic effects of this class of drugs, by binding to these sites. A normal physiological role for these binding sites is unknown, and an endogenous ligand for benzodiazepine receptors has not been definitely identified in normal animals. In animals and human beings with hepatic encephalopathy, however, benzodiazepine receptor antagonists have induced amelioration of the encephalopathy, and an endogenous substance that competitively binds to benzodiazepine receptors has been found in cerebrospinal fluid. These findings suggest that an endogenous ligand for the benzodiazepine receptor with agonist properties contributes to hepatic encephalopathy by promoting GABA-ergic neurotransmission. PMID- 2893877 TI - Growth in children treated for acute lymphoblastic leukaemia. AB - Growth was assessed in 82 children with acute lymphoblastic leukaemia (ALL) who achieved complete continuous first remission following treatment. 34 received prophylactic cranial irradiation at a total dose over 2000 cGy (group I) and 48 at a dose of 1800 cGy (group II). Chemotherapy was given over two or three years and was more intense in group II. Both groups showed a similar significant decrease in height standard deviation score (SDS) over four years (group I -0.31, group II -0.39). 15 children in group I were followed to ten years and continued to show restricted growth with a mean height SDS decrease of -0.84 (range 0 to 1.7). The greatest reduction in yearly decrements in height SDS occurred in the first year after diagnosis. In both groups height SDS increased significantly on completion of chemotherapy. Thus chemotherapy protocols contribute to growth retardation in ALL. In most of these children the mean loss of height over ten years was not sufficiently great to justify long-term growth hormone (GH) therapy. PMID- 2893878 TI - Right atrial electrocardiography in placement of central venous catheters. AB - Right atrial electrocardiography has been used both for the positioning of ventriculoatrial shunts and for the detection and treatment of air embolism during neurosurgical procedures. Its use for the precise placement of central venous catheters for parenteral nutrition is described here. 50 lines were placed in 48 patients. The lines were satisfactorily sited in 48 cases. No false negative or false-positive traces were obtained. The technique is extremely accurate; failure to obtain the characteristic traces indicates malposition of the catheter tip. The need for on-table radiography is virtually eliminated. PMID- 2893880 TI - Treatment of malaria. PMID- 2893879 TI - Campylobacter-like organisms in patient with Menetrier's disease. PMID- 2893881 TI - Reduced sensitivity of Plasmodium falciparum to mefloquine in West Africa. PMID- 2893882 TI - Spouse-related drug side-effects. PMID- 2893883 TI - Cardiopulmonary resuscitation: whose job? PMID- 2893884 TI - Enterohepatic circulation of morphine. PMID- 2893885 TI - Place of GIFT in infertility services. PMID- 2893886 TI - Gambiense trypanosomiasis acquired from needle scratch. PMID- 2893887 TI - "Blind" laboratory analysis. PMID- 2893888 TI - Captopril in patients with ileus. PMID- 2893890 TI - Tracing of laboratory contamination: quality control approach. PMID- 2893889 TI - Interferon and myalgic encephalomyelitis. PMID- 2893891 TI - Opportunistic pneumonia caused by Legionella bozemanii. PMID- 2893892 TI - Listeriosis and food-borne transmission. PMID- 2893893 TI - Aeolus versus cavitation. PMID- 2893894 TI - Multivitamin supplementation and continuous ambulatory peritoneal dialysis. PMID- 2893895 TI - Agency nurses and violence in a psychiatric ward. PMID- 2893897 TI - Helmets for cyclists? PMID- 2893896 TI - The reality of NHS cuts. PMID- 2893898 TI - Water standards for fluoride. PMID- 2893899 TI - Growth retardation in asthmatic children treated with inhaled beclomethasone dipropionate. PMID- 2893900 TI - Advantages of high-dose inhaled budesonide. PMID- 2893901 TI - Chloramphenicol use and childhood leukaemia. PMID- 2893902 TI - Cadmium in lung tissue as marker for smoking. PMID- 2893904 TI - Histopathological study of subcutaneous drug infusion sites in patients dying of cancer. PMID- 2893903 TI - Residual carcinoma-in-situ of contralateral testis after chemotherapy. PMID- 2893905 TI - Peripheral adrenoceptors and type A behaviour. PMID- 2893906 TI - Specificity of iodobenzylguanidine scanning in neuroblastoma. PMID- 2893907 TI - Reticulin antibody, arthritis, and coeliac disease in children. PMID- 2893908 TI - Propofol infusion for the treatment of status epilepticus. PMID- 2893909 TI - Post-exposure prophylaxis against HIV infection in health care workers. PMID- 2893911 TI - Postnatal transmission of HIV infection. PMID- 2893910 TI - Eye protection, HIV, and orthopaedic surgery. PMID- 2893912 TI - Aspirin and rheumatic fever. PMID- 2893913 TI - Endogenous tumour necrosis factor in cancer patients. PMID- 2893914 TI - Primary dysplasia of bladder. PMID- 2893915 TI - Death of a soldier: accident or neglect? PMID- 2893916 TI - Double-blind placebo-controlled comparison of digoxin and xamoterol in chronic heart failure. The German and Austrian Xamoterol Study Group. AB - 433 patients aged 29-80 with mild to moderate heart failure entered a multicentre double-blind randomised between-patient comparison of xamoterol 200 mg twice daily, digoxin 0.125 mg twice daily, and placebo. Patients were assessed at baseline and after three months. Of 349 who completed the double-blind phase, 300 had valid exercise tests. Compared with placebo, xamoterol significantly increased exercise duration and work done on a bicycle ergometer and improved breathlessness and tiredness during daily life as assessed by visual analogue scale and by Likert scale. Digoxin showed no statistically significant advantage over placebo on any of the measures except the Likert scale. Exercise performance and work done were significantly higher with xamoterol than with digoxin. PMID- 2893917 TI - Natural history of localised prostatic cancer managed by conservative therapy alone. AB - The natural history of localised prostatic cancer was studied prospectively over 7 years. Within a single health district all patients with histologically confirmed cancer and negative 99mTc bone scans were managed, irrespective of clinical stage or pathological grade, according to a conservative regimen that included no form of anti-cancer treatment other than endoscopic resection for relief of urinary symptoms. Complete records were compiled on 120 of 152 patients (mean age 74.8 years, range 62-90) without metastases at diagnosis. Local tumour increased to palpable dimensions (T2/T3) in 100 of these patients (84%) but metastases developed in only 13, the mean time to scan conversion being 35.8 months. 23 patients were withdrawn from study and treated because of concern about increasing tumour size, and metastases developed in 1 of these. 5 patients died of prostatic cancer but the disease was not responsible for 48 additional deaths. Actuarial survival rates (excluding non-cancer deaths) at 5 and 7 years were 80% and 75%, respectively; the corresponding rate for those with metastases at presentation was 13% at 5 years. The likelihood that prostatic cancer will cause death within 7 years is indicated primarily by the scintigraphic findings at diagnosis. PMID- 2893918 TI - Screening for phenylketonuria mutations by DNA amplification with the polymerase chain reaction. AB - Single base substitutions have been identified in two mutant phenylalanine hydroxylase (PAH) alleles that cause phenylketonuria (PKU). The two mutant alleles are common among caucasians of northern European ancestry; detection in genomic DNA samples of patients and carriers by hybridisation with oligonucleotides specific for the respective mutant alleles requires fractionation of restriction-enzyme-digested genomic DNA samples by gel electrophoresis. This method is too cumbersome for mass screening of PKU carriers. Identification of carriers of the mutant alleles was achieved by direct analysis of their genomic DNA samples after specific amplification of a sub genomic DNA fragment containing both mutation sites by polymerase chain reaction. The results suggest that it is technically feasible to develop a programme for carrier detection of the genetic trait in the population for individuals without a family history of PKU. PMID- 2893919 TI - Molecular basis of mitochondrial myopathies: polypeptide analysis in complex-I deficiency. AB - Clinical and biochemical data are reported for three patients with mitochondrial myopathy. One patient presented only with exercise-induced muscle weakness, whereas the other two showed signs of multisystem disease. Polarographic determination of oxygen uptake in skeletal muscle mitochondria suggested complex I (nicotinamide adenine dinucleotide [reduced] ubiquinone oxidoreductase) deficiency. Sodium dodecyl sulphate polyacrylamide gel electrophoresis and immunoblotting with antibody to the holoenzyme of complex-I and specific antibodies to certain of the Fe-S subunits of complex-I showed a relatively normal profile in the least affected patient and a generalised reduction in the intensities of all crossreacting bands in the other two patients. The most severely affected patient also showed a disproportionate and pronounced reduction in the 24 K Fe-S subunit. Clinical severity of muscle involvement correlated with the biochemical deficiency as determined polarographically and with the immunoblot appearances. PMID- 2893920 TI - Cohort study of intestinal infection with campylobacter in Mexican children. AB - A cohort of 179 children under 5 years of age from a low-income urban community was followed up for a year to determine the incidence of symptom-producing and of diarrhoea-free campylobacter intestinal infections, and thus their illness-to infection ratio. 66% of all children had at least one campylobacter infection, one-third of these being associated with diarrhoea. The annual incidence of all campylobacter infections was 2.1 episodes per child. The incidence was inversely related to age (r = -0.78 p less than 0.02). The illness-to-infection ratio, which in infants younger than 6 months was 1:2, was negatively associated with age (r = -0.7, p less than 0.02). Only symptom-producing infections occurring early in life seemed to protect against subsequent infections. PMID- 2893921 TI - Neopterins in clinical medicine. PMID- 2893922 TI - Malaria, mosquito control, and primary health care. PMID- 2893923 TI - DNA topoisomerases--new twists to tumour therapy. PMID- 2893924 TI - Solitary rectal ulcer. PMID- 2893925 TI - Chronic sinus node disease and coronary artery disease. PMID- 2893926 TI - Duplex ureter. PMID- 2893927 TI - Increased perinatal mortality among children of mothers exposed to measles during pregnancy. AB - A survey done after a severe epidemic of measles in an urban area of Guinea Bissau has shown that children born to women exposed to measles during pregnancy had a perinatal mortality rate of 15%, compared with only 4% for other children in the community (OR = 4.2; 95% CI 2.1-8.5). None of the women had clinical evidence of measles. Adjusting for background variables, logistic regression analysis showed no tendency towards reduced risk of perinatal mortality among children of women exposed during pregnancy relative to controls. Both stillbirth and early neonatal mortality rates were increased. A similar tendency was found in a rural epidemic (OR = 9.5; 95% CI 2.6-35.1). Exposure during any trimester of fetal life increased the rate of perinatal mortality. The results suggest that exposure to measles virus or some concomitantly transmitted pathogen may contribute to the high perinatal mortality risk found in many developing countries. The possible long-term health consequences of exposure to measles virus should be considered when assessing the value of measles control programmes. PMID- 2893928 TI - Potential effect of revising the CDC surveillance case definition for AIDS. AB - The Centers for Disease Control (CDC) revised the surveillance case definition for acquired immunodeficiency syndrome (AIDS) in August, 1987. To determine the impact of this revision, information was extracted from the medical charts of the 630 patients receiving comprehensive medical care as of 1980 at 6 haemophilia treatment centres, and who were therefore likely to have been infected with human immunodeficiency virus (HIV). 38 (6%) and 47 (7%) met the 1985 and 1987 case definitions, respectively (22% increase). Of the cases added by use of the 1987 case definition, 3 patients had HIV dementia, 3 had Pneumocystis carinii pneumonia (2 of whom were presumptively diagnosed and 1 who had been receiving steroids and immunosuppressives), and 3 had HIV wasting syndrome. These data suggest that the revision of the AIDS case definition will have a substantial impact on future AIDS surveillance trends in persons with haemophilia and perhaps in other risk groups. PMID- 2893929 TI - Topoisomerases in human disease. AB - Topoisomerases are DNA-modifying enzymes that are becoming increasingly important in clinical practice. These enzymes form a target for antibiotics, autoantibodies, and antitumour drugs, and may also be involved in the pathogenesis of certain genetic disorders. Strategies for clinical manipulation of these nuclear enzyme targets are discussed. PMID- 2893930 TI - Another trial that failed. AB - A double-blind comparison of clonidine and lofexidine in the management of the opioid withdrawal syndrome encountered several difficulties of a non-scientific nature which eventually forced termination of the trial. There were, for example, problems with research beds, self-discharges, staff attitudes, access to haematological monitoring, and worries about exposure to staff to human immunodeficiency virus. The trial collapsed when the manufacturers stopped making lofexidine on commercial grounds and the charitable foundation which was backing the trial withdrew its support. Some of the insecurities of medical research may have little to do with scientific merit. PMID- 2893932 TI - Epidural baclofen for intractable spasticity. PMID- 2893931 TI - Hospital-acquired Escherichia coli O157:H7 associated haemolytic uraemic syndrome in a nurse. PMID- 2893933 TI - Sciatica induced by primary epidural adhesions. PMID- 2893934 TI - Ursodeoxycholic acid in biliary atresia. PMID- 2893936 TI - Differential diagnosis between non-A, non-B hepatitis and fatty liver by measurement of urinary neopterin. PMID- 2893935 TI - Controlled clinical trial of homoeopathy in postoperative ileus. PMID- 2893937 TI - HLA-DQ polymorphism in rheumatoid arthritis. PMID- 2893938 TI - Presumed congenital rubella syndrome: virus embryopathy or hereditary disease? PMID- 2893939 TI - Patient-triggered ventilation prevents pneumothorax in premature babies. PMID- 2893940 TI - Carcinoma-in-situ germ-cells exfoliated from seminiferous epithelium into seminal fluid. PMID- 2893941 TI - Assessing radiation risks. PMID- 2893942 TI - Severe dapsone syndrome due to weekly maloprim. PMID- 2893945 TI - Restenosis after angioplasty. PMID- 2893944 TI - Home treatment of deep-vein thrombosis. PMID- 2893943 TI - Thrombolytic therapy and percutaneous coronary angioplasty. PMID- 2893946 TI - Khat-chewing in the Near East. PMID- 2893947 TI - Impact of surgery in locally advanced breast cancer. PMID- 2893948 TI - Manipulating broken noses. PMID- 2893949 TI - Unusual treatment of massive pharyngeal pouch. PMID- 2893951 TI - Mycobacterial culture: what temperature? PMID- 2893950 TI - Clostridium tertium and the gut. PMID- 2893952 TI - Human parvovirus B19 and hydrops fetalis. PMID- 2893953 TI - B19 parvovirus infection of myocardial cells. PMID- 2893954 TI - Dapsone and remission of Crohn's disease. PMID- 2893956 TI - Benzodiazepines in anxiety. PMID- 2893955 TI - Antimycobacterial chemotherapy in two cases of inflammatory bowel disease. PMID- 2893957 TI - Intralesional injection of cyclosporin in psoriasis. PMID- 2893958 TI - How accurate are bibliographic data bases? PMID- 2893959 TI - "Drug dumping" in donations to Sudan. PMID- 2893960 TI - Alternative to "aaah". PMID- 2893961 TI - Sugars in baby and infants' drinks. PMID- 2893962 TI - Decrease in acute hepatitis B incidence continued in 1987. PMID- 2893963 TI - Oral rehydration with fizz but no chloride. PMID- 2893964 TI - Screening for ovarian cancer by CA-125 measurement. PMID- 2893965 TI - Strict product liability. PMID- 2893966 TI - GABA-B receptor activation and conflict behaviour. AB - Baclofen and oxazepam enhance extinction of conflict behaviour in the Geller Seifter test while baclofen and diazepam release punished behaviour in Vogel's conflict test. In order to investigate the possibility that the effect of the selective GABA-B receptor agonist baclofen is mediated indirectly via the GABA A/benzodiazepine receptor complex, the effect of pretreatment of rats with baclofen on [3H]-diazepam binding to washed and unwashed cortical and cerebellar membranes of rats has been studied. Baclofen pretreatment increased Bmax in washed cerebellar membranes when bicuculline was present in the incubation mixture. No effect was seen in cortical membranes. The present results render it unlikely that the effect of baclofen on extinction of conflict behaviour and punished drinking is mediated via the GABA-A/benzodiazepine receptor complex. PMID- 2893967 TI - Further analysis of the neuropharmacological profile of 9-amino-1,2,3,4 tetrahydroacridine (THA), an alleged drug for the treatment of Alzheimer's disease. AB - In a recent study we have documented the acetylcholinesterase and outward K+ current inhibiting activity of 9-amino-1,2,3,4-tetrahydroacridine (THA), a drug reportedly active in the treatment of Alzheimer patients. In the present study we investigated the effects of THA on the uptake and release of radiolabeled NA, DA and 5-HT. THA concentration-dependently inhibited the uptake of these monoamines with IC-50 values of approximately 1, 7 and 2 microM respectively. Release studies of these radiolabeled monoamines from control and reserpine pretreated tissue revealed that the THA-induced uptake inhibition does not occur at the level of the axonal membrane but at the level of the monoaminergic storage granules. In addition the affinity of THA for alpha-1, alpha-2 and beta adrenoceptors, for D-2 dopamine, S-1a and S-2 serotonin and for muscarinic receptors was investigated. It appeared that in concentrations up to 1 microM THA did not display any affinity towards these receptors. It is concluded from these experiments that the effects of THA on monoaminergic neurotransmission might contribute to the alleged therapeutic action of THA in Alzheimer's disease. PMID- 2893969 TI - Overload protection: avoidance response to heavy plantar surface loading. AB - Current footwear which are designed for use in running are examples of intentional biomechanical model integration into device design. The inadequacy of this footwear in protecting against injury is postulated to be due to fixation on inadequate models of locomotory biomechanics that do not provide for feedback control; in particular, an hypothesized plantar surface sensory-mediated feedback control system, which imparts overload protection during locomotion. A heuristic approach was used to identify the hypothesized system. A random series of loads (0 to 164 kg) was applied to the knee flexed at 90 degrees. In this testing system, plantar surface avoidance behavior was the difference between the sum of the leg weight and the load applied to the knee, and the load measured at the plantar surface; this was produced by activation of hip flexors. Significant avoidance behavior was found in all of the subjects (P less than 0.001). On all surfaces tested, including modern athletic footwear (P less than 0.001), its magnitude increased directly in relation to the load applied to the knee (P less than 0.001). There were significant differences in avoidance behavior in relation to the weight-bearing surfaces tested (P less than 0.05). With the identification of a feedback control system which would serve to moderate loading during locomotion, an explanation is provided as to why current athletic footwear do not protect and may be injurious; thus allowing the design of footwear which may be truly protective. PMID- 2893968 TI - Cocaine and central monoaminergic neurotransmission: a review of electrophysiological studies and comparison to amphetamine and antidepressants. AB - Psychomotor stimulants (e.g. cocaine and amphetamine) and many antidepressants are believed to elicit their psychotropic actions by interacting primarily with central monoaminergic neurons. The acute central neuronal effects of amphetamine and antidepressants have been extensively investigated in rats utilizing extracellular single unit electrophysiological and microiontophoretic techniques in vivo. In recent years the chronic effects of these compounds on the above neuronal systems have also been reported. Such investigations have proliferated because of the realization that the mechanisms underlying the psychotomimetic effects (e.g. amphetamine and cocaine) and mood elevation (i.e. antidepressants) observed with the administration of these drugs are more accurately reflected in chronic studies. For many years it has been assumed that cocaine and amphetamine produce very similar if not identical psychotropic effects through their actions on central monoaminergic neurotransmission. In terms of effects on single monoaminergic neurons, this assumption had gone by untested until two years ago, when the first report of the electrophysiological effects of cocaine on central monoaminergic (locus ceruleus) neurons appeared in the literature (61). This review discusses recent electrophysiological studies with cocaine at the level of single identified monoaminergic neurons and compares such data with that previously reported for amphetamine and antidepressants. In addition to identifying some of the similarities and differences between these compounds, this review also highlights some of the gaps in our knowledge regarding the effects of these drugs on central monoaminergic neurotransmission. PMID- 2893970 TI - Somatostatin infusion enhances hepatic glucose production during hyperglucagonemia. AB - Somatostatin (SRIH) is widely employed in metabolic studies to permit quantitation of glucose production and disposal rates while the endocrine pancreas is suppressed and the hormonal milieu is under the investigator's control. In these studies it is assumed that if peripheral levels of insulin and glucagon are the same during SRIH infusion as during control studies, the effects of these hormones on glucose metabolism are equivalent. If the effect of glucagon is influenced by SRIH infusion, then these techniques may be unsuitable for the study of the regulation of hepatic glucose output. To assess the influence of SRIH on glucagon-stimulated hepatic glucose production (Ra), we determined Ra during paired studies in ten healthy (five younger and five older) subjects. In each study an insulin infusion designed to yield physiologic systemic insulin levels of 20 to 30 microU/mL was given from 0 to 210 minutes. In addition, from 60 to 210 minutes either glucagon alone (3.5 ng/kg/min) (I + IRG) or glucagon (3.5 ng/kg/min) and SRIH (250 micrograms/h) (I + IRG + SRIH) was infused. Since results for plasma levels of insulin, C-peptide, glucagon, and Ra were similar in young and old subjects, the two age groups were combined for analysis. Basal plasma insulin, glucagon, C-peptide, glucose, and Ra were similar in each arm of the study. Insulin values were nearly identical from 60 to 210 minutes (I + IRG, 23.8 +/- 1.1; I + IRG + SRIH, 24.0 +/- 1.0 microU/mL).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893971 TI - Mechanical effect of vocalization on human brain and meninges. AB - Vibrations of human skull, as produced by loud vocalisation, exert a massaging effect on the brain and facilitate elution of metabolic products from the brain into the cerebrospinal fluid (CSF). In addition, these vibrations, through their effect on arachnoid villi, speed up the flow of CSF from the subarachnoid space into the blood within the superior sagittal sinus and lacunae lateralis. In this way, the speed of renewal of CSF is increased, which again contributes to a faster cleaning process of the brain. The most important feature of human evolution is enlargement of the brain. This by itself would not be enough. The Neandertals had a brain 15% larger than we have, yet they did not survive in competition with modern humans. Their brains were more polluted, because their massive skulls did not vibrate and therefore the brains were not sufficiently cleaned. In the evolution of modern humans the thinning of cranial bones was important. In addition, the chin remained jutting out of the face as in no other hominids, in order to maintain the distance from the chin to the hyoid bone equal to the distance from the latter to the styloid process. This situation facilitates transmission of laryngeal vibrations onto the skull base via the mandible. PMID- 2893976 TI - Comparison of repeated DNA from strains of Entamoeba histolytica and other Entamoeba. AB - Restriction enzyme digestion patterns of total genomic DNA revealed the presence of highly repeated DNA in Entamoeba histolytica and E. histolytica-like (Laredo type) amoebae of humans, E. invadens and E. invadens and E. terrapinae of reptiles, and E. moshkovskii isolated from sewage polluted waters. Homology with Plasmodium berghei ribosomal DNA was striking. Northern blot analysis of E. histolytica RNA provided further evidence that the highly repeated DNA codes for ribosomal RNA. The distribution of restriction enzyme sites on repeated DNA of the Entamoeba was highly polymorphic. Thus it was possible, based on EcoRI digestion patterns, to distinguish between strains of E. histolytica and the other species of Entamoeba. Additionally, these investigations at the molecular level corroborate previously reported physiological and biochemical evidence indicating the E. histolytica-like amoebae and E. histolytica are not conspecific. EcoRI fragments from repeated DNA of E. histolytica (strain HM-1: IMSS) were cloned in the plasmid vector pTZ18R. A subfragment from one of these clones proved to be a useful hybridization probe in distinguishing E. histolytica from the other Entamoeba. PMID- 2893975 TI - Gene exchange in African trypanosomes: characterisation of a new hybrid genotype. AB - We describe the isolation of a hybrid Trypanosoma brucei clone following the mixed cyclical transmission of two parental clones through tsetse flies. The characterisation of this clone reveals some new facets of the process of genetic exchange in T. brucei. The inheritance of four isoenzyme loci and restriction fragment polymorphisms at two loci was interpretable in 'mendelian' genetic terms, involving meiosis either before or after the genetic exchange event. However, at a further two isoenzyme loci a deviation from mendelian behaviour was observed. Pulse field gel analysis showed that the hybrid clone possessed a new combination of intermediate size chromosomes. Examination of kinetoplast DNA variants showed uniparental kinetoplast inheritance, and with reference to previous work we conclude that the kinetoplast can be inherited from either parent. The nuclear DNA content of the hybrid clone was measured and found to be identical to the parental nuclear DNA contents. This finding, together with the inheritance of isoenzyme and RFLP markers, is discussed with respect to possible models for genetic exchange. PMID- 2893974 TI - Autogenous regulation of histone mRNA decay by histone proteins in a cell-free system. AB - We tested the hypothesis that histone mRNA turnover is accelerated in the presence of free histone proteins. In an in vitro mRNA decay system, histone mRNA was degraded four- to sixfold faster in reaction mixtures containing core histones and a cytoplasmic S130 fraction than in reaction mixtures lacking these components. The decay rate did not change significantly when histones or S130 was added separately, suggesting either that the histones were modified and thereby activated by S130 or that additional factors besides histones were required. RecA, SSB (single-stranded binding), and histone proteins all formed complexes with histone mRNA, but only histones induced accelerated histone mRNA turnover. Therefore, the effect was not the result of random RNA-protein interactions. Moreover, histone proteins did not induce increased degradation of gamma globin mRNA, c-myc mRNA, or total poly(A)- or poly(A)+ polysomal mRNAs. This autoregulatory mechanism is consistent with the observed accumulation of cytoplasmic histone proteins in cells after DNA synthesis stops, and it can account, in part, for the rapid disappearance of histone mRNA at the end of S phase. PMID- 2893978 TI - Additions to departments of medicine. PMID- 2893977 TI - Sequence homology of surface membrane proteins of Babesia rodhaini. AB - Four surface membrane proteins of Babesia rodhaini have previously been shown to induce a degree of protective immunity, and to carry both unique and cross reactive determinants. cDNA clones for two of the genes coding for these proteins have been isolated and used as probes to isolate a single large genomic DNA fragment which contained all four genes. DNA sequence of two of the genes and their predicted amino acid sequences confirmed that the proteins had hydrophobic sequences at their N- and C-termini, an observation consistent with their proposed cell surface location. Homologies in both amino acid and nucleotide sequences were found at the 3'and at the 5' ends, but considerable sequence variations existed elsewhere in the genes and their products. The genes coding for these four proteins were tandemly arranged along a single relatively short length of chromosome, and such structures, because of their sequence homologies, probably could have arisen by gene duplication. The extensive variation suggested that there may be a functional need for these proteins to be different or capable of varying, although computer analysis implied that the extent of this variation may be constrained by structural requirements. This variation could be indicative of a role for these proteins in the host-parasite relationship or immune evasion. PMID- 2893980 TI - The discriminative stimulus properties of histamine H1 antagonists in d amphetamine-trained and midazolam-trained pigeons. PMID- 2893979 TI - Treatment effectiveness: medical staff and services provided to 2,394 patients at methadone programs in three states. PMID- 2893982 TI - Biological evaluation of compounds for their physical dependence potential and abuse liability. X. Drug testing programs of the Committee on Problems of Drug Dependence, Inc. (1986). PMID- 2893981 TI - A cyclic somatostatin analog that precipitates withdrawal in morphine-dependent mice. AB - We evaluated the ability of the mu selective, peptidic, opioid antagonist CTP to precipitate withdrawal in morphine-dependent mice after intracerebroventricular (i.c.v.) and subcutaneous (s.c.) administration. The withdrawal syndrome evoked by i.c.v. CTP was different in some respects from that observed after i.c.v. naloxone. Naloxone, given i.c.v., produced shakes and tremors, defecation, diarrhea, wet dog shakes, jumping and weight loss. In contrast, the prominent signs following i.c.v. CTP were grooming, tremors and shakes, defecation, wet dog shakes and weight loss. CTP treated mice exhibited a greatly reduced incidence of jumping behaviors and diarrhea. While s.c. naloxone evoked similar effects to i.c.v. naloxone, CTP given s.c. stimulated defecation and modest weight loss only. The differences in the profile of withdrawal signs between naloxone and CTP may be related to their differences in receptor selectivity or possibly to their respective alkaloidal and peptidic natures. The relative lack of behavioral effects seen after s.c. CTP probably reflects the inability of CTP to pass through the blood brain barrier, and indicates that although the majority of withdrawal signs are mediated by centrally located opioid receptors, the gastrointestinal tract can be withdrawn independently of the central nervous system. PMID- 2893973 TI - Bacterial adenosine 5'-triphosphate synthase (F1F0): purification and reconstitution of F0 complexes and biochemical and functional characterization of their subunits. PMID- 2893985 TI - Serum lipids in muroid virus nephropathy. PMID- 2893983 TI - The role of a low beta 1-adrenoceptor selectivity of [3H]CGP-12177 for resolving subtype-selectivity of competitive ligands. AB - On the basis of saturation binding studies on rat cardiac microsomes, which contained a mixed population of beta-adrenoceptor subtypes, [3H]CGP-12177 is presumed to be a non-selective beta-adrenergic radioligand. However, saturation binding studies carried out in the presence of subtype-saturating concentrations of the beta 2-selective antagonist ICI 118,551 and the beta 1-selective antagonist ICI 89,406, respectively, revealed a KD for beta 1-adrenoceptors of 0.33 +/- 0.02 nmol/l and a KD for beta 2-adrenoceptors of 0.90 +/- 0.14 nmol/l. Competition experiments with the highly selective antagonists revealed greatly different competition binding curves in the presence of either [3H]CGP-12177 or ( )[125I]iodocyanopindolol (ICYP), a beta-adrenergic radioligand considered to be as non-selective as [3H]CGP-12177. The following results are further suggestive for a selectivity of [3H]CGP-12177 for beta 1-adrenoceptors: (1) Using non-linear regression analysis, a significantly lower selectivity (expressed as the ratio of the IC50 for beta 2-adrenoceptors to the IC50 for beta 1-adrenoceptors) as well as a larger proportion of beta 1-adrenoceptors were calculated by competition of the beta 1-selective antagonist ICI 89,406 with [3H]CGP-12177 binding than by competition of ICI 89,406 with ICYP binding; (2) reducing the [3H]CGP-12177 concentration from 2 to 0.4 nmol/l, competition experiments with ICI 89,406 led to an increase in the estimated selectivity of the competitor and in the estimated proportion of beta 1-adrenoceptors; (3) reverse findings were obtained with ICI 118,551, a beta 2-selective antagonist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2893984 TI - Urinary enzyme excretion after donor nephrectomy. AB - A number of recent studies of long-term kidney donors have reviewed glomerular function and blood pressure. Little attention has been paid to the potentially damaging effects of compensatory hyperfiltration on renal tubular cells after donor nephrectomy. The urinary excretion of high-molecular-weight enzymes is a sensitive indicator of renal tubular cell damage. This study compares the urinary excretion of four enzymes (alanine aminopeptidase, alkaline phosphatase, N-acetyl beta-D-glucosaminidase, and lactate dehydrogenase) in a group of 77 subjects who had undergone unilateral nephrectomy up to 21 years previously with 52 healthy non-nephrectomized controls. The urinary excretion for all four enzymes by the remaining kidney after contralateral nephrectomy in the kidney donors was significantly greater than the enzyme excretion per single kidney in the control group (p less than 0.001). No correlation was found between the degree of enzymuria and either glomerular filtration rate or time since nephrectomy. The elevated activity of urinary enzymes in kidney donors may be related to increased metabolism by the renal tubular cells after contralateral nephrectomy. This study suggests that long-term compensatory hyperfiltration does not damage tubular cells, at least over this time scale. PMID- 2893987 TI - Functional coupling of gamma-aminobutyric acid (GABA)A and benzodiazepine type II receptors: analysis using purified GABA/benzodiazepine receptor complex from bovine cerebral cortex. AB - Possible functional coupling between gamma-aminobutyric acid (GABA) and benzodiazepine receptors was examined using a purified GABA/benzodiazepine receptor complex. The purified receptor complex was obtained by 1012-S-acetamide adipic hydrazide Sepharose 4B affinity column chromatography, following the solubilization of synaptic membrane from the bovine cerebral cortex with Nonidet P-40. The binding of [3H]GABA to the purified GABA receptor was displaced significantly by muscimol and bicuculline, GABAA receptor agonists and antagonists, respectively, but not by baclofen, a GABAB receptor agonist. On the other hand, the binding of [3H]flunitrazepam to the purified benzodiazepine receptor was found to be displaced by microM ranges of CL 218,872, which is known to be sensitive to the benzodiazepine type II receptor. Furthermore, it was found that the binding of [3H]muscimol to these purified GABAA receptors was enhanced by benzodiazepines, while the binding of [3H]flunitrazepam to these benzodiazepine type II receptors was increased by GABA receptor agonists. These enhancements by GABA agonists and benzodiazepine agonists were found to be blocked by bicuculline and a benzodiazepine receptor antagonist, Ro15-1788, respectively. These results strongly suggest that the purified receptor may consist of GABAA and benzodiazepine type II receptors and possess a functional coupling of these sites, as shown in cerebral synaptic membranes. PMID- 2893986 TI - Immediate and long-term effects of 3,4-methylenedioxymethamphetamine on serotonin pathways in brain of rat. AB - In the rat, administration of the psychoactive analog of amphetamine 3,4 methylenedioxymethamphetamine (MDMA), causes selective, pronounced decreases in markers of central serotonergic function. The time course of these neurochemical changes was examined in several serotonergic nerve terminal regions of the brain. Fifteen min after subcutaneous injection of MDMA (10 mg/kg), the enzymatic activity of tryptophan hydroxylase (the rate-limiting enzyme for the biosynthesis of serotonin) was significantly decreased in the frontal cortex; by 1 hr after the injection, the activity of tryptophan hydroxylase had significantly declined in the neostriatum, hippocampus and hypothalamus as well. Although extensive recovery had occurred by 2 weeks, the activity of the enzyme remained significantly depressed in most regions. Decline of the regional content of 5 hydroxytryptamine (5-HT) closely paralleled, but was usually preceded by, that of the enzyme. Concentrations of the primary metabolite of 5-HT, 5 hydroxyindoleacetic acid (5-HIAA), were less responsive: in most regions levels of 5-HIAA had significantly decreased by 3 hr, but not by 1 hr, following treatment. Markers of dopamine function were altered transiently but had returned to control values by 24 hr. Administration of multiple doses of MDMA (5 doses over a 24-hr period) resulted in significant decreases in serotonergic parameters for up to 110 days after treatment. The rate and extent of recovery varied according to both the dose administered and the region examined. The persistence of these serotonergic deficits suggests that MDMA induced the destruction of serotonin-containing axon terminals. PMID- 2893972 TI - Molecular basis of transmembrane signal transduction in Dictyostelium discoideum. PMID- 2893988 TI - Toxicity of p-methoxyphenol to dopamine neurons in the rat substantia nigra. AB - Local injections of p-methoxyphenol into the substantia nigra of rats led to a mildly dose-related destruction of dopamine neurons as indicated by reductions of dopamine and its metabolites in the ipsilateral striatum and by loss of tyrosine hydroxylase immunoreactivity in the injected substantia nigra. Both Nissl staining of the injected nucleus and measurement of noradrenaline and serotonin in the ipsilateral striatum indicated some selectivity of the toxic action. PMID- 2893989 TI - Electrophysiological evidence for a non-opioid interaction between dynorphin and GABA in the substantia nigra of the rat. AB - Interactions between neuronal responses mediated by dynorphin A1-8 and GABA were investigated in the substantia nigra zona reticulata. Extracellular recordings and microiontophoresis were performed using five-barrel microelectrodes in chloral hydrate-anesthetized male rats. When iontophoresed alone, dynorphin A1-Q significantly inhibited the firing of 22% of the neurons tested. The inhibition was rapid in onset and recovery and was dose-dependent. In another 22% of the cells, iontophoretic dynorphin produced an increase in the baseline firing rate which was slow in both onset and offset; the remaining 56% were unaffected by dynorphin. When GABA and dynorphin A1-8 were applied in conjunction, the inhibitory action of GABA was attenuated in 61% of the cells; whereas, when dynorphin and GABA were ejected simultaneously onto the cells that were inhibited by dynorphin A1-8, the respective inhibitory effects of dynorphin and GABA appeared to be additive. The kappa antagonist, MR-2266, failed to block the ability of dynorphin A1-8 to attenuate the action of GABA. In addition, the non opiate peptide des-tyr-dynorphin A2-17, produced effects similar to that of dynorphin A1-8. The role of dynorphin in the basal ganglia and its interaction with the other major transmitter in the substantia nigra zona reticulata, GABA, is discussed. PMID- 2893990 TI - Differential effects of serotonin on the spontaneous discharge and on the excitatory amino acid-induced responses of deep cerebellar nuclei neurons in rat cerebellar slices. AB - The effects of steady iontophoretic applications of serotonin on the spontaneous discharge and on the excitatory responses induced in deep cerebellar nuclei neurons by iontophoretic pulse applications of L-glutamate, L-aspartate, N-methyl D,L-aspartate and quisqualate were studied in rat cerebellar slices maintained in vitro. Serotonin increased the spontaneous firing rate of deep cerebellar nuclei neurons in 91% of the tested cells by 109% on the average and had no effect on the remaining recorded neurons. Conversely, the monoamine induced a depression of the excitatory responses induced by four agonists tested and the depressant potency of serotonin was in the order quisqualate, glutamate, aspartate, N-methyl D,L-aspartate. These effects persisted in low calcium high magnesium solution, suggesting that the serotonin receptors involved in these phenomena were, at least partially, postsynaptically located. The serotonin-induced increase in the cell firing rate appeared to be methysergide-resistant whereas the serotonin induced decrease in the responses elicited by excitatory amino acids was depressed by this antagonist, which could indicate that these differential effects of serotonin are mediated via different mechanisms and/or serotonin receptor subtypes. PMID- 2893991 TI - The adrenergic agonist tizanidine has differential effects on flexor reflexes of intact and spinalized rat. AB - Tizanidine with its predominant alpha 2-adrenergic properties is a potent myorelaxant drug used clinically in spastic patients. The aim of this study is to analyse further the mechanisms by which this substance exerts its influence on spinal reflexes. It was found that tizanidine dose-dependently diminished flexor reflexes in intact chloralose-anaesthetized rats, and also, but slightly less, in unanaesthetized decerebrate rats. In spinalized rats (1-5 days postoperatively), flexor reflexes were, however, enhanced by tizanidine, especially by the higher doses. Pretreatment with the alpha 2-blocker yohimbine antagonized the depressant action of tizanidine in intact rats whereas the alpha 1-blocker prazosin antagonized the facilitatory action of tizanidine in the spinalized rats. The reflex depression might be explained by a removal of a tonic facilitation of spinal neurons by the descending noradrenergic fibres, because tizanidine is likely to reduce, like clonidine, the spontaneous activity of locus coeruleus neurons by presynaptic autoinhibition. In spinalized preparations, a net facilitatory alpha 1-mediated action may be revealed by the higher doses of tizanidine that would be unopposed by the alpha 2-mediated disfacilitation. PMID- 2893993 TI - An immunohistochemical study of the acute and long-term effects of 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine in the marmoset. AB - Administration of the drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induces a parkinsonian syndrome in primates. Intraperitoneal injections of 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine in the common marmoset (Callithrix jacchus) produced symptoms of rigidity, akinesia and tremor which persisted for at least one month. However, after this time, considerable behavioural recovery occurred, although animals were still severely bradykinetic compared with controls. Marmosets were allowed to survive for 1, 3 1/2 or 7 months prior to histological and immunocytochemical analysis. Detection of catecholaminergic neurons using antibodies directed against the enzyme tyrosine hydroxylase revealed a profound (80%) loss of dopaminergic cells from the substantia nigra one month after initiation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment. This was accompanied by a severe gliosis. Fewer cells were lost from the adjacent ventral tegmental area (45%), but dopamine-containing cells in other brain areas were not obviously affected. At longer survival times the substantia nigra was less damaged, with a proliferation of glia in the pars compacta and a loss of approximately 20% of the dopaminergic perikarya. Using immunohistochemical techniques, the distribution of neuropeptides substance P, [Met]enkephalin and dynorphin 1-17-like immunoreactivity were examined and found to exhibit distinctive patterns in the marmoset substantia nigra. The integrity of these systems appeared intact at all times after 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine treatment. These results support the hypothesis that the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine produces a clinical syndrome, indistinguishable from Parkinson's disease, via a selective destruction only of neurons with perikarya in the substantia nigra pars compacta and the ventral tegmental area. The findings that the peptidergic input to these cells together with most non-nigral dopaminergic cell groups are not damaged, indicate that the selectivity of the lesion produced by 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine appears greater than that seen in idiopathic Parkinson's disease. The neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the marmoset may not be permanent since both behavioural and biochemical recovery were observed after several months. PMID- 2893992 TI - Nerve fibers surrounding intracranial and extracranial vessels from human and other species contain dynorphin-like immunoreactivity. AB - Dynorphin B(20-32) was visualized by immunohistochemistry in guinea-pig and rat perivascular nerve fibers and was measured by radioimmunoassay within the walls of feline, canine, bovine and human cephalic and systemic arteries and veins. Canine vessels contained the highest levels. When human blood vessels or trigeminal ganglia were subjected to reverse-phase high-performance liquid chromatography, dynorphin immunoreactivity exhibited a retention time identical to that of synthetic dynorphin B. No differences in dynorphin-like immunoreactivity were measurable between feline systemic arteries and veins, or between cephalic and systemic vessels. The highest amounts were present in leptomeninges devoid of large pial arteries. Relatively high levels were also measured in feline and human trigeminal ganglia and feline superior cervical and sphenopalatine ganglia, three sources of projecting perivascular axons. Levels did not diminish, however, in ipsilateral feline cephalic vessels following either unilateral trigeminal or superior cervical ganglionectomies. Hence, dynorphin-containing fibers may project from parasympathetic cell bodies or perhaps from intrinsic brain sources. Previously published reports indicate that the kappa agonist dynorphin does not modify vessel tone when added in vitro but does inhibit release of neurotransmitters from afferent and sympathetic axons via prejunctional receptors. These observations suggest a pharmacological role for dynorphin on sensory and autonomic functions of the vasculature. PMID- 2893994 TI - Pharmacological evidence that alpha 1-adrenoceptors mediate metamorphosis of the Pacific oyster, Crassostrea gigas. AB - Oyster larvae can be induced to metamorphose by exposure to the natural vertebrate adrenergic agonists, epinephrine and norepinephrine. The larval receptors mediating this induction were pharmacologically characterized by testing the ability of a variety of adrenergic agonists and selected structural analogs of epinephrine and norepinephrine to induce oyster metamorphosis, and by testing the ability of various adrenergic antagonists to block the induction of metamorphosis by epinephrine. Oyster metamorphosis can be induced by vertebrate adrenergic agonists with relative potencies: cirazoline greater than epinephrine greater than phenylephrine greater than or equal to norepinephrine greater than alpha-methylnorepinephrine greater than isoproterenol much greater than methoxamine = clonidine. Other structural analogs of epinephrine and norepinephrine, including dopamine and octopamine, were ineffective at inducing metamorphosis. Induction of metamorphosis by epinephrine can be blocked by vertebrate adrenergic antagonists with relative potencies: chlorpromazine greater than or equal to prazosin greater than phentolamine greater than WB4101 greater than propranolol greater than yohimbine greater than metoprolol. These data demonstrate that receptors similar to vertebrate-type alpha 1-adrenoceptors mediate oyster metamorphosis. This is the first evidence for alpha 1 adrenoceptors in molluscs, and provides an important clue to the control of the complex process of molluscan metamorphosis and to the evolution of vertebrate adrenergic receptors. PMID- 2893995 TI - Brainstem projections to spinal motoneurons: an update. AB - 1. The existence of direct projections to spinal motoneurons and interneurons from the raphe pallidus and obscurus, the adjoining ventral medial reticular formation and the locus coeruleus and subcoeruleus is now well substantiated by various anatomical techniques. 2. The spinal projections from the raphe nuclei and the adjoining medial reticular formation contain serotonergic and non serotonergic fibres. These projections also contain various peptides, several of which are contained within the serotonergic fibres. Whether still other transmitter substances (e.g. acetylcholine) are present in the various descending brainstem projections to motoneurons remains to be determined. 3. The spinal projections from the locus coeruleus and subcoeruleus are mainly noradrenergic, but there also exists a non-noradrenergic spinal projection. 4. Pharmacological, physiological and behavioural studies indicate an overall facilitatory action of noradrenaline and serotonin (including several peptides) on motoneurons. This may lead to an enhanced susceptibility for excitatory inputs from other sources. 5. The brainstem areas in question receive an important projection from several components of the limbic system. This suggests that the emotional brain can exert a powerful influence on all regions of the spinal cord and may thus control both its sensory input and motor output. PMID- 2893998 TI - Cutaneous polyarteritis nodosa. PMID- 2893997 TI - [New muscle relaxants: effect on intracranial pressure and on cerebral perfusion pressure]. PMID- 2893996 TI - Evidence for a neurotransmitter function of acetylcholine in rabbit superior colliculus. AB - Acetylcholinesterase staining and studies on the uptake of [3H]choline into the subsequent efflux of tritium from collicular slices were carried out in order to provide evidence for a neurotransmitter function of acetylcholine in rabbit superior colliculus. Acetylcholinesterase staining was dense and homogeneous in superficial layers whereas the staining was arranged in patches with slightly higher density caudally than rostrally in the intermediate layers. The accumulation of tritium in slices incubated with [3H]choline depended on time, temperature and concentration, and was inhibited by hemicholinium-3. Accumulation was slightly higher in caudal than in rostral slices. Electrical stimulation enhanced tritium outflow from slices preincubated with [3H]choline. Tetrodotoxin and a low calcium medium inhibited the evoked overflow whereas hemicholinium-3 caused an enhancement. Oxotremorine decreased the evoked overflow; atropine prevented this effect. The opioids [D-Ala2, MePhe4, Glycol5]enkephalin, [D-Ala2, D-Leu5]enkephalin and ethylketocyclazocine caused an inhibition. The effects of the latter two agonists were antagonized by naloxone. The GABAB-receptor-agonist (-)-baclofen decreased the evoked overflow at lower concentrations than GABA, whereas the GABAA-receptor-agonist muscimol was ineffective. Serotonin produced an inhibition which was prevented by metitepin, alpha- and beta-adrenoceptor as well as dopamine-receptor ligands caused no change. It is concluded that in the rabbit superior colliculus the pattern of acetylcholinesterase staining is comparable, but not identical to the distribution in other species. The accumulation of [3H]choline, as well as the tetrodotoxin-sensitive and calcium dependent overflow of tritium upon electrical stimulation (reflecting presumably release of [3H]acetylcholine) indicate that acetylcholine has a neurotransmitter function in this tissue. The release of [3H]acetylcholine was modulated by various transmitter substances and related compounds. The pattern of modulation of release differed from the pattern in other cholinergically innervated tissues. PMID- 2893999 TI - Orbital T-cell lymphoma in human T-cell leukemia virus-I infection. AB - This is the first report of orbital involvement in systemic adult T-cell leukemia/lymphoma (ATLL). The etiologic agent of ATLL is the human T-cell leukemia virus-I (HTLV-I), the first retrovirus demonstrated to induce cancer in humans. The diagnosis of ATLL is based on characteristic clinicopathologic features in combination with serologic or virologic evidence of HTLV-I infection. Serum antibodies to HTLV-I were identified by immunofluorescent microscopy. Viral particles characteristic of HTLV-I were found in a culture of the patient's peripheral blood lymphocytes. The patient was a native of the Caribbean, one of the known endemic foci of HTLV-I infection. Adult T-cell leukemia/lymphoma should be considered in the differential diagnosis of orbital T-cell lymphomas. PMID- 2894000 TI - Polymorphism of the human c-abl gene: relation to incidence and course of chronic myelogenous leukemia. AB - Abnormalities in structure and expression of the proto-oncogene c-abl have been implicated in the genesis of chronic myelogenous leukemia (CML). We studied leukemic cell DNA from 42 CML patients for evidence of rearrangement and/or amplification of c-abl analogous to that described in the CML cell line K562. Using the enzymes Bgl II, Pst I, Xba I, seven patients demonstrated an atypical Southern blot pattern similar to that found in K562. Analysis of DNA from normal controls and skin fibroblast from one of the seven patients established that the atypical blot pattern was due to a restriction fragment length polymorphism rather than a gene rearrangement. Further analysis revealed that c-abl exists as two alleles, A and B, yielding three genotypes: AA, AB and BB. Inheritance was Mendelian. With respect to allele A, allele B contains a deletion of about 1 kb lying in a intronic region in close proximity to highly repetitive Alu sequences and the sequence coding for phosphotyrosine of the c-abl protein. K562 and the seven patients with similar Southern patterns were identified as AB heterozygotes. In K562, only the A allele was amplified. The frequencies of AA and AB genotypes in 37 Caucasian CML patients were 81.1% and 18.9% and in 57 unrelated normal Caucasian controls 87.7% and 12.3%, not significantly different. The BB genotype was identified in less than 1% of Caucasians. Of note, five AB patients who developed a terminal blast crisis demonstrated a 4:1 lymphoid:myeloid crisis ratio in contrast to a 2:7 lymphoid:myeloid crisis ration in nine AA patients and a similar ratio in mixed AA and AB historical controls. Otherwise, CML patients with AA and AB genotypes manifested similar clinical parameters. No patients demonstrated amplification of c-abl and analysis of four AB patients for loss of one c-abl allele during the course of their disease was negative. Thus, amplification of c-abl and loss of one c-abl allele are both infrequent in CML and do not play a significant role in the course of the disease. PMID- 2894001 TI - A single point mutation responsible for c-mos polymorphism in cancer patients. AB - A rare EcoRI restriction fragment length polymorphism (RFLP) in the 3' end of the human c-mos locus has been identified in DNA from patients with breast tumors, esophageal carcinomas and leukemias. Until now, this RFLP has not been found in normal populations, suggesting that its presence may reflect some cancer susceptibility. To characterize this RFLP, we have isolated both alleles of the c mos locus from DNA of a breast cancer patient and determined the nucleotide sequence of the polymorphic region. Our results show that this RFLP is due to a single nucleotide substitution (T instead of C), resulting in the disappearance of EcoRI site. PMID- 2894002 TI - Restriction fragment length polymorphisms of the human N-myc gene: relationship to gene amplification. AB - Using Southern blot hybridization with N-myc probes, we observed two restriction fragment length polymorphisms (RFLPs) in the Japanese population. One of the RFLPs was accounted for by the presence (allele S1) or absence (S2) of a SphI site in the second intron of the N-myc gene, and the other was explained by the presence (P1) or absence (P2) of a PvuII site in the 3' region of the gene. The allele frequencies of P1 and P2 were not significantly differently between the normal population and neuroblastoma patients with the minor allele frequency being 38-40% for P2. Frequencies of the S1 allele were 28% and 24% in neuroblastoma patients and the normal population, respectively. Fewer S1S1 homozygotes and more S1S2 heterozygotes than expected were observed in the normal population. No individuals with the S1P2 haplotype were observed due to an extreme linkage disequilibrium between the two RFLP loci. Amplification of N-myc in embryonal tumors was random with respect to the P allele, and strictly associated with the S2 allele in six cases of fresh tumors and three cases of cultured cell lines. PMID- 2894003 TI - HRAS1 proto-oncogene polymorphisms in human malignant melanoma: TaqI defined alleles significantly associated with the disease. AB - We have analysed the DNA of peripheral blood leukocytes (PBL) from 55 melanoma patients and 53 healthy individuals and failed to find any significant association between melanoma and rare HRAS1 alleles defined by MspI/HpaII digestion. However, the analysis of the same DNAs for a different polymorphism based on the presence of additional TaqI sites in the variable tandem repeat region of HRAS1 showed that the total frequency of a group of allelic variants, named Tp, was significantly higher in melanoma patients than in normal donors. PMID- 2894004 TI - The Medical Practice Act of 1985. Part IX--Implementing the regulations for non physician health care professionals. PMID- 2894005 TI - Enzymuria in neonates during treatment with tobramycin or ceftazidime. PMID- 2894006 TI - Health assessment and screening during adolescence. PMID- 2894007 TI - A BanII dimorphic site located in the third intron of the human apolipoprotein AI (APOA1) gene. PMID- 2894008 TI - NcoI dimorphic site located 8kb 3' to the human apolipoprotein AIV (APOA4) gene. PMID- 2894010 TI - Isolation and mapping of a polymorphic DNA sequence (pMCA1-1) on chromosome 15 [D15S33]. PMID- 2894009 TI - A frequent HindIII RFLP on chromosome 3p21-25 detected by a genomic erbA beta sequence. PMID- 2894011 TI - Isolation and mapping of a polymorphic DNA sequence pMCT46.2 on chromosome 15 [D15S26]. PMID- 2894013 TI - Isolation and mapping of a polymorphic DNA sequence pEFD4.2 on chromosome 19 [D19S22]. PMID- 2894012 TI - Isolation of mapping of a polymorphic DNA sequence pEFZ10 on chromosome 18 [D18S22]. PMID- 2894014 TI - Isolation and mapping of a polymorphic DNA sequence pJCZ3.1 on chromosome 19 [D19S20]. PMID- 2894015 TI - Use of patient-controlled analgesia in surgical oncology patients. PMID- 2894017 TI - [Effect of somatostatin on the biological availability of phenazone in healthy men]. PMID- 2894016 TI - [Effect of adrenomimetic drugs on the blood vessels of the genital organs of swine during the estrous cycle]. AB - The flow in uterine artery (ua) and ovarian artery (oa) was measured in isolated reproductive organs of sows perfounded with own blood of the animal or with Krebs Henseleit fluid at the constant pressure of 100 mm Hg applying the haemotachometric method. Controlling parallel to the flow, the condition of tension in smooth muscle of the organ, the sensitivity of vessels of ua and oa areas to: norepinephrine (NA), phenylephrine (F), epinephrine (A) and isoprenaline (I) on the 1-2, 13-14 and 16-18 days of oestrous cycle was investigated. It was found that the blood flow in the vessels under investigation diminishes after intraarterial application of alpha-adrenomimetic NA and F and after ambi-receptor acting A, while it increases after beta-adrenomimetic I. It was also shown, that the vessels of the area oa are many times less sensitive to the applied agents than the vessels of the ua area. During the oestrous cycle significant changes in sensitivity of both areas to adrenomimetic agents take place. The highest sensitivity to NA, A and F simultaneous with the lowest sensitivity to I were noted in the ua area on 13-14 days. On the 16-18 and 1-2 days of the cycle the diminished sensitivity to NA, A and F and increased to I comparing with the 13-14 day was found. Also, the vessels of the oa area show the lowest sensitivity to NA, A and F and the highest to I on the 1-2 day of the cycle. It is the highest to NA and F on the 13-14 day and is accompanied by the lowest sensitivity to I. The sensitivity on 13-14 day is similar to that on 16-18 day. The sensitivity of oa area to A increases from the lowest on 1-2 days to the highest on 16-18 day of the cycle. PMID- 2894018 TI - The influence of histamine receptor antagonists on antinociceptive action of narcotic analgesics. AB - The influence of some antagonists of histamine receptors on morphine-, fentanyl-, and pentazocine-induced analgesia was studied in rats and mice. H1-receptor antagonists (benzhydramine mepyramine) potentiated analgesic action of morphine and fentanyl. Given alone in high doses they also induced a naloxone non reversible analgesia. Analgesic effects of pentazocine were not changed by benzhydramine and mepyramine. H2-receptor antagonist-cimetidine enhanced also analgesia induced by morphine and fentanyl in rats, but it either increased (after icv injection of 50 micrograms) or decreased (after icv injection of 100 micrograms) the action of pentazocine. Thus, H1 and H2 antagonists potentiate the antinociceptive effects of morphine and fentanyl but the action of pentazocine is not changed by H1 antagonists and is affected in an inconsistent manner by a H2 antagonist cimetidine. It seems that the potentiating effect of H-antagonists is related to the opioid mu receptors. PMID- 2894019 TI - Differences in the development of tolerance to various benzodiazepines. AB - Anticonvulsant, sedative and anxiolytic effects of the following benzodiazepines, administered chronically by the intraperitoneal route, were assessed: nitrazepam (NTZ), diazepam (DZ), oxazepam (OXZ), chlordiazepoxide (CDX) and temazepam (TMZ). The action of NTZ in tests for sedative, anticonvulsant and anxiolytic effects rapidly changed upon a repeated daily treatment, which suggests development of tolerance, while no tolerance developed to such effects of OXZ. The stimulating effect of DZ was found not earlier than after 5 weeks of chronic treatment, but no tolerance to the anxiolytic action was observed, and the anticonvulsant action was even potentiated. The stimulating action and tolerance to the anxiolytic effects of CDX and TMZ developed rapidly, but was accompanied with an only slight decrease in the anticonvulsant effect. PMID- 2894020 TI - Effect of somatostatin and dopamine on the activity of cyclic AMP-independent protein kinase from human placenta. AB - Studies in the effect of somatostatin and dopamine on the incorporation of 32P from ATP to casein and ribosomes were carried out using purified protein kinase type II, isolated from the human placental cytosol. Low concentrations of somatostatin inhibited, while high ones of dopamine concentrations stimulated the activity of kinase. PMID- 2894021 TI - Intractable duodenal ulceration. PMID- 2894022 TI - Effects of propiomazine on the EEG sleep of normal subjects. AB - The effects of 25 mg propiomazine were examined in ten healthy volunteers in a sleep laboratory setting. A significant decrease in sleep latency and a corresponding decrement in subjectively assessed sleep latency was found during drug treatment. The distribution of the different sleep stages was affected to a relatively small extent. Some evidence for a suppression of REM-sleep in the early part of the treatment period was found. Based on subjective assessment, the subjects rated their sleep quality as significantly improved during treatment. Ratings of "drowsiness in the morning" were not different during baseline and drug treatment, but there was a significant decrease at withdrawal. PMID- 2894023 TI - [HIV-2 infections in heroin addicts]. PMID- 2894024 TI - Inhibition of the adhesion of Entamoeba histolytica trophozoites to human erythrocytes by carbohydrates. AB - We have analyzed the effect of 14 carbohydrates (seven monosaccharides, four disaccharides and three aminosugars) on the adhesion of Entamoeba histolytica HK9 trophozoites to human red blood cells (RBC). Amebal adhesion was significantly inhibited by five of these carbohydrates with the following order of potency: lactose (Lac) greater than N-acetylgalactosamine (GalNac) greater than melibiose (Mel) greater than galactose (Gal) greater than N-acetylglucosamine (GlcNAc). The mean inhibitory concentration of Lac was 2.66 mM. Adhesion increased by 20% in the presence of 5.5 mM glucose (Glc). Inhibition of the adhesion was lower in the absence rather than in the presence of Glc only with Gal-NAc, whereas it was similar with Lac, Mel, Gal, and GlcNAc in both cases. The initial rate of amebal adhesion decreased 27% by RBC fixation, but adhesion to fixed RBC was also inhibited by the same five carbohydrates. Inhibition was higher in mixtures containing Lac, GalNAc, and Mel, than with the same isolated carbohydrates; Lac + Gal-NAc was the most potent mixture. Inhibition decreased when Lac, GalNAc, and Mel were mixed either with Gal or GlcNAc. We conclude that E. histolytica adhesion depends on amebal metabolic energy generated from Glc and on several surface components of RBC, some of which are inactivated with glutaraldehyde whereas others are inhibited by sugars containing Gal, GlcNAc, or Gal-NAc residues. PMID- 2894025 TI - Antiamoebic activity of chonemorphine, a steroidal alkaloid, in experimental models. AB - Chonemorphine, a steroidal alkaloid isolated from Chonemorpha fragrans Moon (Apocyanaceae) was identified as an antimoebic principle during the course of a screening programme for novel antiparasitic agents from plant sources. At a dosage of 100 mg/kg x 4 chonemorphine led to a 100% cure of experimental hepatic infection in golden hamsters and cleared 90% of the intestinal infection in weanling Wistar rats at 200 mg/kg (x4) dosages. The discovery of chonemorphine as an antiamoebic agent is an addition to the few known plant amoebicides such as emetine and conessine. PMID- 2894026 TI - In vivo study of glucose-induced somatostatin secretion: comparison in normal and alloxan-diabetic dogs. AB - This work was undertaken to study the effect of glucose on pancreaticoduodenal and peripheral venous somatostatin-like immunoreactivity (SLI) levels in dogs. Our experiments were performed in normal and alloxan diabetic dogs, conscious or anesthetized. The response of somatostatin was studied following intravenous (0.2 g/kg) or oral (1 g/kg) glucose administration. SLI levels were assayed in peripheral venous blood and in superior pancreaticoduodenal venous blood. An interplay of the cholinergic nervous system was challenged both after oral and intravenous glucose load by a prior administration of atropine sulfate (0.2 mg/kg i.v.). Our results show that (a) peripheral venous SLI levels do not reflect pancreatic D-cell activity in alloxan diabetic as in normal animals. (b) Increase of peripheral venous SLI level after oral glucose is under cholinergic nervous system control. (c) In alloxan diabetic dogs, the response of pancreaticoduodenal venous SLI to intravenous glucose was decreased, whereas peripheral SLI response to oral glucose was increased. PMID- 2894027 TI - Restoration of phototrophic growth in a mutant of Chlamydomonas reinhardtii in which the chloroplast atpB gene of the ATP synthase has a deletion: an example of mitochondria-dependent photosynthesis. AB - The Chlamydomonas reinhardtii mutant FUD50 has a deletion in the atpB gene of the chloroplast ATP synthase [Woessner, J. P., Masson, A., Harris, E. H., Bennoun, P., Gillham, N. W., and Boynton, J. E. (1984) Plant Mol. Biol. 3, 177-190]. We have isolated a suppressed strain (FUD50su) that can grow under phototrophic conditions, although it still showed no synthesis of the beta subunit of coupling factor 1. Thylakoid membranes of the FUD50su strain were similar to those of the original FUD50 strain, in that they both lacked all the subunits making up the chloroplast ATP synthase complex. We show that photosynthesis in FUD50su is sensitive to inhibitors such as antimycin, specific for mitochondrial electron transport. This observation indicates that photosynthesis in the FUD50su strain is achieved through an unusual interaction between mitochondria and chloroplast. Exportation of light-induced reduced compounds from the chloroplast to the mitochondria elicits ATP formation in the latter, and ATP is subsequently imported to the chloroplast. The activation of such an ATP shuttle coupled to an NADPH shuttle would thus provide the reducing power and the free energy needed for carbon assimilation in a chloroplast that lacks chloroplast ATP synthase. PMID- 2894029 TI - Transcellular proton current in Achlya bisexualis hyphae: relationship to polarized growth. AB - Growing hyphae of Achlya bisexualis drive an electric current through themselves, such that positive charge flows into the apical region (the anterior 300 micron) and exits distally along the hyphal trunk. They also generate a gradient of extracellular pH, such that the medium surrounding the apex is slightly alkaline whereas that along the hyphal trunk is acid. To explore the genesis of these gradients and their relationship to polarized extension, we examined the effects of changes in the composition of the growth medium. The transcellular electric current was most pronounced in medium rich in amino acids. In leaner medium, containing limited amounts of amino acids or none at all, the current was attenuated or absent. We interpret the results to mean that inward current represents H+/amino acid symport, mediated by porters that are preferentially localized in the apical region. Apical alkalinity may be due to ammonia production. Outward current, and perhaps also the generation of metabolic acid, reflects the distribution of the H+-ATPase, which is excluded from the apex but is abundant along the hyphal trunk. Thanks to the spatial segregation of transport functions, protons characteristically flow into the apical region. However, since hyphae grow apically and at the same rate despite wide variations in current pattern, the flow of electric charge through the hyphae cannot be required to polarize extension or to localize the tip. PMID- 2894028 TI - Isolation of a cDNA clone for the gamma subunit of the chloroplast ATP synthase of Chlamydomonas reinhardtii: import and cleavage of the precursor protein. AB - A cDNA library from Chlamydomonas reinhardtii, constructed in the phage expression vector lambda gt11, was probed with antiserum directed against the nuclear-encoded gamma subunit of the chloroplast H+-transporting ATP synthase [ATP phosphohydrolase (H+-transporting) or chloroplast coupling factors 0 and 1, EC 3.6.1.34] of C. reinhardtii. A cDNA was isolated and transcribed in vitro. The transcript was translated in vitro and immunoprecipitated with anti-gamma-subunit serum to yield a product that coelectrophoresed with the immunoprecipitated product from in vitro-translated polyadenylylated RNA. These proteins were larger than the mature gamma subunit, either immunoprecipitated as chloroplast coupling factor 1 or as the individual subunit. Thus, the gamma subunit is synthesized as a precursor of greater molecular weight in C. reinhardtii. Furthermore, the precursor protein encoded by the cDNA is imported into pea chloroplasts and processed to a lower molecular weight polypeptide that coelectrophoreses with mature C. reinhardtii gamma subunit. The largest cDNA isolated is about the same length as the corresponding mRNA (approximately equal to 1900 bases long) and probably contains the entire coding region. Southern blot analyses revealed restriction fragment length polymorphisms and that the gamma subunit is probably encoded by an intron-containing single-copy gene. PMID- 2894030 TI - Consistent chromosome 3p deletion and loss of heterozygosity in renal cell carcinoma. AB - Renal cell carcinoma (RCC) and normal kidney tissues have been examined from 34 patients with sporadic, nonhereditary RCC. Eighteen of the 21 cytogenetically examined tumors (86%) had a detectable anomaly of chromosome arm 3p distal to band 3p11.2-p13, manifested as a deletion, combined with the nonreciprocal translocation of a segment from another chromosome or monosomy 3. Restriction fragment-length polymorphism analysis showed loss of D1S1 heterozygosity in 16 of the 21 cases (76%). D3S2 heterozygosity was lost in 2 of 11 cases (18%). The variability of the breakpoint between 3p11.2 and 3p13 and the absence of a consistently translocated segment from another chromosome suggests a genetic-loss mechanism, while the activation of a dominant oncogene appears less likely. Together with the previously demonstrated involvement of the 3p14.2 region in a familial case, these findings suggest that RCCs may arise by the deletion of a "recessive cancer gene," as do retinoblastoma and Wilms tumor. The relevant locus must be located on the telomeric side of the D1S1 locus on the short arm of chromosome 3. PMID- 2894031 TI - Exon-intron organization and sequence comparison of human and murine T11 (CD2) genes. AB - Genomic DNA clones containing the human and murine genes coding for the 50-kDa T11 (CD2) T-cell surface glycoprotein were characterized. The human T11 gene is approximately equal to 12 kilobases long and comprised of five exons. A leader exon (L) contains the 5'-untranslated region and most of the nucleotides defining the signal peptide [amino acids (aa) -24 to -5]. Two exons encode the extracellular segment; exon Ex1 is 321 base pairs (bp) long and codes for four residues of the leader peptide and aa 1-103 of the mature protein, and exon Ex2 is 231 bp long and encodes aa 104-180. Exon TM is 123 bp long and codes for the single transmembrane region of the molecule (aa 181-221). Exon C is a large 765 bp exon encoding virtually the entire cytoplasmic domain (aa 222-327) and the 3' untranslated region. The murine T11 gene has a similar organization with exon intron boundaries essentially identical to the human gene. Substantial conservation of nucleotide sequences between species in both 5'- and 3'-gene flanking regions equivalent to that among homologous exons suggests that murine and human genes may be regulated in a similar fashion. The probable relationship of the individual T11 exons to functional and structural protein domains is discussed. PMID- 2894032 TI - Cholinergic regulation of protein phosphorylation in bovine adrenal chromaffin cells. AB - Chromaffin cells were isolated from bovine adrenal medullae and maintained in primary culture. After prelabeling with 32PO4, exposure of the chromaffin cells to acetylcholine increased the phosphorylation of a Mr approximately equal to 100,000 protein and a Mr approximately equal to 60,000 protein (tyrosine hydroxylase), visualized after separation of total cellular proteins in naDodSO4/polyacrylamide gels. Immunoprecipitation with antibodies to three known phosphoproteins ("100-kDa," "87-kDa," and protein III) revealed an acetylcholine dependent phosphorylation of these proteins. These three proteins were also shown to be present in bovine adrenal chromaffin cells by immunolabeling techniques. "100-kDa" is a Mr approximately equal to 100,000 protein selectively phosphorylated by calcium/calmodulin-dependent protein kinase III, "87-kDa" is a Mr approximately equal to 87,000 protein selectively phosphorylated by protein kinase C, and protein III is a phosphoprotein doublet of Mr approximately equal to 74,000 (IIIa) and Mr approximately equal to 55,000 (IIIb) phosphorylated by cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase I. Furthermore, 100-kDa was shown to be identical to the Mr approximately equal to 100,000 protein whose phosphorylation was increased by acetylcholine treatment. The acetylcholine-dependent increase in phosphorylation of tyrosine hydroxylase, 100-kDa, 87-kDa, and protein III required extracellular calcium and was mimicked by nicotine, veratridine, elevated K+, and calcium ionophore A23187, but not by muscarine. In addition, forskolin increased the phosphorylation of tyrosine hydroxylase, 100-kDa, and protein III, but not that of 87-kDa. Phorbol 12,13 dibutyrate increased the phosphorylation of tyrosine hydroxylase, 87-kDa, and protein III, but not that of 100-kDa. The data demonstrate that cholinergic activation of chromaffin cells increases the phosphorylation of several proteins and that several protein kinase systems may be involved in these effects. PMID- 2894033 TI - Phenol emulsion-enhanced DNA-driven subtractive cDNA cloning: isolation of low abundance monkey cortex-specific mRNAs. AB - To isolate cDNA clones of low-abundance mRNAs expressed in monkey cerebral cortex but absent from cerebellum, we developed an improved subtractive cDNA cloning procedure that requires only modest quantities of mRNA. Plasmid DNA from a monkey cerebellum cDNA library was hybridized in large excess to radiolabeled monkey cortex cDNA in a phenol emulsion-enhanced reaction. The unhybridized cortex cDNA was isolated by chromatography on hydroxyapatite and used to probe colonies from a monkey cortex cDNA library. Of 60,000 colonies screened, 163 clones were isolated and confirmed by colony hybridization or RNA blotting to represent mRNAs, ranging from 0.001% to 0.1% abundance, specific to or highly enriched in cerebral cortex relative to cerebellum. Clones of one medium-abundance mRNA were recovered almost quantitatively. Two of the lower-abundance mRNAs were expressed at levels reduced by a factor of 10 in Alzheimer disease relative to normal human cortex. One of these was identified as the monkey preprosomatostatin I mRNA. PMID- 2894034 TI - Effects of 2,3-iminosqualene on cultured cells. AB - 2,3-Iminosqualene (ISq) is a powerful inhibitor of squalene oxide:lanosterol cyclase (EC 5.4.99.7). When added to lipid-depleted culture media (LDM) of rat hepatoma (H-4-II-E-C3) or Chinese hamster ovary (CHO) cells at a concentration of 10 micrograms ml-1, it causes the cells to float off the substratum in a few days. Lipoproteins in the culture medium completely counteract this effect. Cells in lipoprotein-containing media (FGM) grow normally in the presence of ISq. Irrespective of the culture medium, ISq at 10 micrograms ml-1 causes an almost complete and apparently irreversible inactivation of the squalene oxide cyclase in CHO and H4 cells and the accumulation in the cells of squalene, of squalene 2,3-oxide (mostly), and of squalene 2,3-22,23-dioxide when [14C]acetate or [14C]mevalonate is fed to the cells. Chronic treatment of H4 cells with ISq failed to elicit induction of the cyclase, but increased the conversion of mevalonate into squalene and squalene dioxide, and depressed the conversion of squalene oxide to the dioxide. Cells loaded with squalene and the squalene oxides from mevalonate in the presence of ISq get rid of these substances by rapidly secreting them into the media and by some unidentified metabolic processes. PMID- 2894035 TI - Parallel processing of binocular disparity in the cat's retinogeniculocortical pathways. AB - In the cat, parallel streams of information processing have been traced from X-, Y- and W-type retinal ganglion cells to visual cortical areas 17 (X-, Y- and W type), 18 (Y-type) and 19 (W-type). In the present study we have examined, in the anaesthetized and paralysed adult cat, the role played by X-, Y- and W subsystems, projecting to areas 17 and 19, in the processing of binocular retinal disparity. The tapetal reflection technique was used to monitor residual eye movements and to provide a map, for each eye, of the retinal blood vessels which could later be compared with retinal wholemounts stained with cresyl violet to reveal the area centralis. The receptive-field disparities of cells recorded from areas 17 and 19 were compared with each other and with reference to the visual axes defined by the area centralis of each eye. Cells of area 19 (receiving W type input) had horizontal receptive-field disparities that were significantly more divergent than those of the cells in area 17 and 17-18 'border region'. Referred to the area centralis, the mean horizontal receptive-field disparity in area 19 was -0.5 degrees (+/- 0.8 degrees). The mean horizontal receptive-field disparity of area 17 (receiving X-, Y- and W-type input) was convergent with respect to the visual axis at +2 degrees (+/- 0.5 degrees). Finally, the mean horizontal receptive-field disparity of the cells in the 17-18 border region (which receive mainly Y-type input) was even more convergent (2.6 degrees +/- 1.5 degrees) than that of area 17. Binocular interactions of cortical neurons were tested with the Risley biprism technique. Area 19 cells had maximal responses to binocular stimulation when the receptive-field disparities were either close to zero or slightly divergent. In contrast, area 17 cells tended to respond optimally to disparities that were either slightly or strongly convergent. At the level of the lateral geniculate nucleus there were significant differences between the receptive-field disparities inferred from the comparison of receptive field positions of adjacent neurons recorded on either side of the border between the A and A1 geniculate laminae and those inferred from a similar comparison at the C1-C2 border. The mean horizontal disparities inferred from the interlaminar comparison at the A-A1 border were +2.1 degrees (+/- 0.3 degrees); those inferred from the interlaminar comparison at the C1-C2 border -0.2 (+/- 0.2 degrees) were more divergent.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2894036 TI - [Anticonvulsive action of beta-receptor blockers in maximum electroshock in mice]. PMID- 2894037 TI - [The effect of beta receptor blockers on the anticonvulsive action of phenobarbital in maximum electroshock in mice]. PMID- 2894038 TI - Rational use of anxiolytic drugs. PMID- 2894039 TI - Pyrimidinones as biodynamic agents. PMID- 2894040 TI - Mechanism of action of anxiolytic drugs. PMID- 2894042 TI - [Molecular mechanisms of multidrug resistance]. PMID- 2894041 TI - The automated Tail Suspension Test: a computerized device which differentiates psychotropic drugs. AB - 1. Mice when suspended by the tail will alternate between active attempts to escape and immobility. Immobility like that measured in the behavioral despair test is reduced by a wide variety of antidepressant agents. 2. The present paper describes a computerized version of this test (ITEMATIC-TST) which in addition to recording immobility measures the power of the movements. 3. Various tricyclic (amitriptyline, desipramine, imipramine), MAOI (clorgyline, moclobemide, nialamide, pargyline, toloxatone) and atypical antidepressants (bupropion, citalopram, indalpine, mianserin, nomifensine, viloxazine) were tested and compared with psychostimulants (d-amphetamine, caffeine), neuroleptics (chlorpromazine, haloperidol, sulpiride), anxiolytics (clobazam, diazepam) and agents acting on the cholinergic system (atropine, oxotremorine). 4. All antidepressants decreased the duration of immobility and most increased the power of movements. 5. The psychostimulants also decreased immobility but only amphetamine increased the power of movements. 6. Neuroleptics increased immobility without affecting the power of movements, whereas anxiolytics increased immobility but decreased the power of movements. 7. Atropine had a profile similar to antidepressants whereas oxotremorine tended to have opposite effects. 8. The results suggest that the automated test system with its two parameters is not only sensitive to antidepressants but could also be useful for generating activity profiles for different kinds of psychotropic agent. PMID- 2894043 TI - [Terfenadine compared to clemastine in the treatment of pruriginous cutaneous diseases. Double-blind comparative study]. PMID- 2894044 TI - [Somatostatin in upper digestive hemorrhage. Results of a random controlled study]. PMID- 2894045 TI - [Cimetidine, ranitidine and somatostatin in the medical treatment of acute and chronic Zollinger-Ellison syndrome]. PMID- 2894046 TI - [Pharmacological analyses of the vascular responses to beta-blockers in isolated and perfused coronary and femoral arteries of dogs]. PMID- 2894047 TI - [Isolation of Clostridium perfringens from cooked meat foods]. PMID- 2894048 TI - [Prophylactic strategy in biliary lithiasis]. PMID- 2894049 TI - [Gastrointestinal peptides. Their importance in digestive physiology and pathology]. PMID- 2894050 TI - [Silent myocardial ischemia]. PMID- 2894051 TI - [Pathogenesis of rheumatic carditis]. PMID- 2894052 TI - [Vasodilator treatment in pulmonary hypertension]. PMID- 2894053 TI - [Alcoholic cardiomyopathy--an etiological factor in cardiomegaly generating heart failure]. PMID- 2894054 TI - [Clinical study of patients hospitalized with urinary infections at the Medical Clinic II of the Bucharest Municipal Clinical Hospital 1980-1984]. PMID- 2894055 TI - [The information value of determining serum sorbitol dehydrogenase activity in liver diseases]. PMID- 2894056 TI - [Digitalis bradycardia: an often neglected adverse effect]. PMID- 2894057 TI - [Current developments in antirheumatic medication. I. Anti-inflammatory, immunomodulator and synoviorthesis agents]. PMID- 2894058 TI - [Adverse kidney effects of nonsteroidal anti-inflammatory agents-- current physiopathological and clinical aspects]. PMID- 2894059 TI - [Magnesium and myocardial necrosis]. PMID- 2894060 TI - [Fructosamine-blood sugar relationship in diabetes mellitus]. PMID- 2894061 TI - [Can one speak today of nonsurgical treatment in hydatidosis?]. PMID- 2894062 TI - [Clinical characteristics of alcoholic liver diseases]. PMID- 2894063 TI - [Cardiac micropotentials recorded noninvasively by special amplification technics]. PMID- 2894064 TI - [Nifedipine (Corinfar) treatment in acute myocardial infarct]. PMID- 2894066 TI - [Effect of the type of gastric resection on glucose metabolism]. PMID- 2894065 TI - [Cerebrovascular lesions in diabetics (a study of 109 cases)]. PMID- 2894067 TI - [Homonymous atopy]. PMID- 2894068 TI - [Rheumatoid polyarthritis manifestations in a female patient with right atrial myxoma]. PMID- 2894069 TI - Behavioral pharmacology of zopiclone. AB - The pharmacological properties of zopiclone, a cyclopyrrolone derivative, have been studied in comparison with diazepam, nitrazepam, and flurazepam, on behavioral tests in mice and rats, including open-field activity, Skinner box conflict test, hyperemotionality and muricidal behavior of olfactory bulbectomized or raphectomized rats, pentetrazol or electroshock convulsions, inclined screen, rotarod, and thiopental-, ether-, or ethanol-induced anesthesia. Zopiclone exhibited pharmacological properties qualitatively similar to those of benzodiazepines especially in conflict, aggressivity, and pentetrazol-induced convulsion tests. On the other hand, its myorelaxant activity was somewhat weaker than that of the reference drugs. The pharmacological effects of zopiclone were of short duration. PMID- 2894070 TI - Disposition of 5-aminosalicylic acid by 5-aminosalicylic acid-delivering compounds. AB - The disposition of 5-aminosalicylic acid (5-ASA) from 5-ASA-delivering drugs was studied in eight healthy volunteers. Time-related urinary excretion and faecal excretion of 5-ASA and acetyl-5-ASA were measured after a single oral dose of the azo compounds sulphasalazine and olsalazine, of the slow-release compounds Pentasa, Asacol, and Salofalk, and of plain 5-ASA. Plain 5-ASA was rapidly excreted into urine and had a low faecal recovery, indicating fast absorption proximally in the intestine and little availability to the colon. After ingestion of both azo compounds and slow-release compounds, urinary excretion of 5-ASA was markedly delayed and reduced, and faecal excretion was enhanced. At all points of time there was a significant but not very marked difference in urinary excretion of 5-ASA after ingestion of the azo compounds and the slow-release compounds, in favour of the azo compounds. A significantly larger proportion of the ingested 5 ASA, moreover, was excreted in faeces after intake of azo compounds as compared with slow-release compounds. PMID- 2894071 TI - The effect of pancreatectomy and gastroenterectomy on the release of somatostatin and vasoactive intestinal polypeptide in experimental fecal peritonitis. AB - Rats were subjected to laparotomy, to pancreatectomy, to gastroenterectomy (control groups), or to these procedures plus a septic challenge by instillation of 0.1 ml feces intraperitoneally (experimental groups). In the laparotomized controls plasma somatostatin values were significantly higher in samples from the portal vein than from the upper inferior caval vein. After both pancreatectomy and gastroenterectomy a significant fall in plasma somatostatin values was observed, and there was no significant difference between samples taken from the portal vein and the systemic circulation. An intraperitoneal septic challenge elicited a significant rise in portal plasma somatostatin in laparotomized rats, whereas this increase did not occur in pancreatectomized and gastroenterectomized animals, supporting the notion that plasma somatostatin originates from the pancreas and/or the gastrointestinal tract during septic peritonitis. No differences were detected in plasma vasoactive intestinal polypeptide (VIP) values in animals from the three control groups. However, both in laparotomized and in pancreatectomized septic animals a significant rise in plasma VIP was demonstrated in samples from the portal vein. By contrast, no such increase was observed in gastroenterectomized septic rats. Thus, the gastrointestinal tract seems to be the major source of circulating VIP during fecal peritonitis in the rat. PMID- 2894072 TI - Adrenaline stimulates acid production in isolated pig and human parietal cells. AB - To investigate the mechanisms of adrenergic stimulation of the parietal cell and to study the possible relationship between the stress hormone adrenaline and duodenal ulcer, the effects of adrenaline and various adrenoceptor agonists and antagonists were investigated in parietal cells isolated from pig stomachs and from endoscopic biopsy specimens taken from the gastric mucosa of patients. Parietal cell acid production was assayed by the aminopyrine accumulation technique. Adrenaline as the sole drug showed poor or no stimulatory effect but potentiated histamine-stimulated acid production. In the presence of histamine, beta-adrenoceptor agonists caused a stimulation of acid formation with the potency order isoproterenol greater than adrenaline greater than noradrenaline. The beta-2-selective antagonist ICI118551 was a more potent inhibitor of acid production than both the beta-1 antagonist practolol and the H2-receptor antagonist cimetidine. Studies of (3H)-dihydroalprenolol (DHA) binding to purified parietal cell membranes showed a protein-concentration-dependent and specific binding of 2.2 +/- 0.6 pmol DHA/microgram. Adrenaline increased gastric acid production in both pig and human parietal cells, most likely through a beta 2 receptor on the parietal cell. The adrenaline stimulatory effect in cells obtained from patients with peptic ulcer was more pronounced than in cells from non-ulcer patients, which indicates a possible role of adrenaline in some types of ulcer disease. PMID- 2894073 TI - Local nerve blockade by tetrodotoxin induces ectopic phase 3 of the migrating myoelectric complex in dogs. AB - The effect on the migrating myoelectric complex (MMC) of local nerve blockade in the jejunum was studied in five unanesthetized dogs. A silastic catheter was implanted in a terminal branch of a jejunal artery, perfusing a 5- to 10-cm segment, 45 cm below the ligament of Treitz. Small-bowel motor activity was studied electromyographically with implanted electrodes. Three different doses of tetrodotoxin (166, 333, 500 ng/kg/h) were administered intra-arterially for 5 h. During the 333- and 500-ng but not during the 166-ng/kg/h perfusions ectopic activity fronts started just below the perfused segment. At this time no phase-3 activity was observed in the proximal bowel. In addition to ectopic fronts normal MMCs were observed during the perfusions. These observations show that local nerve blockade induces phase-3 activity, probably by inhibiting an inhibitory nerve action. PMID- 2894075 TI - A newly characterized HLA DQ beta allele associated with pemphigus vulgaris. AB - The inheritance of particular alleles of major histocompatibility complex class II genes increases the risk for various human autoimmune diseases; however, only a small percentage of individuals having an allele associated with susceptibility develop disease. The identification of allelic variants more precisely correlated with disease susceptibility would greatly facilitate clinical screening and diagnosis. Oligonucleotide-primed gene amplification in vitro was used to determine the nucleotide sequence of a class II variant found almost exclusively in patients with the autoimmune skin disease pemphigus vulgaris. In addition to clinical implications, the disease-restricted distribution of this variant should provide insight into the molecular mechanisms underlying associations between diseases and HLA-class II genes. PMID- 2894074 TI - Neurobiological studies of sensory gating in schizophrenia. AB - The sensory disturbance in schizophrenia is often described as an inability to filter out extraneous noise from meaningful sensory inputs. The neurobiological basis of this inability to filter has been examined using auditory evoked potentials, which are computerized averages of the brain's electrical response to sound. The sounds are presented in pairs to test the ability of the brain to inhibit, or gate, its response to a repeated stimulus. Schizophrenic patients lack the ability to gate the neuronal response shown by a particular wave, the P50 wave. The measurement of this deficit in human subjects and the exploration of its neurobiology in animals has produced evidence about several issues in the pathophysiology of schizophrenia: (1) the role of dopamine in improvement of sensory function in schizophrenic patients treated with neuroleptic drugs, (2) the interaction between familial or genetic deficits in sensory functioning in schizophrenic patients and possible abnormalities in dopamine metabolism, and (3) a mechanism by which noradrenergic hyperactivity in mania and other psychiatric illnesses might mimic some pathophysiological deficits in schizophrenia. PMID- 2894076 TI - Passage of stone fragments from the gallbladders of dogs. AB - The destruction of gallstones by shock waves leads to a considerable amount of stone fragments in the gallbladder. To test the ability of the stones fragments to leave the gallbladder, kidney stone fragments of 2 or 4 millimeters maximal diameter were implanted into the gallbladders of 16 dogs and passage was observed for five weeks. Independent of stone size, about 35 per cent of the fragments remained in the gallbladder. Transient elevations of enzymes of the liver or pancreas occurred significantly less often with 2 millimeter fragments and were less pronounced. Gross pathologic changes of the papilla of Vater, or dilation of the bile duct were observed with 4 millimeter fragments but not with those that were 2 millimeters. The results of this study suggest that the maximal fragment size after destruction of gallstones should be as small as possible, that is, in the range of 2 millimeters. PMID- 2894078 TI - Clinical examinations with Tinset tablet in pollen rhinitis. PMID- 2894077 TI - The role of leucine in hepatic ketogenesis. AB - Isolated hepatocyte studies demonstrated that leucine can be a precursor of ketone bodies. In this study we examine the relative contribution of leucine to hepatic ketogenesis in vivo. Three groups of conscious dogs with long-term indwelling catheters in the femoral artery, hepatic vein, and portal vein were studied. Group I (n = 3) animals were fasted overnight for 24 hours, and those in groups II and III (n = 4, each) were fasted for 62 to 68 hours (designated 3-day fast). Groups I and III received intravenous saline solution (0.9%) and served as controls. In group II selective acute insulin deficiency (SAID) was induced by a peripheral intravenous somatostatin (SRIF) infusion and intraportal glucagon (0.55 ng/body weight/min). Net hepatic production (NHP) of ketone bodies (kb) and leucine (leu) was measured by the arteriovenous difference technique. Hepatic conversion of leucine to ketone bodies was measured by continuous infusion of L-U [14C]-leucine and by determination of the appearance of [14C]-ketone bodies across the liver. In the group fasted overnight NHPleu was 0.02 +/- 0.01 mumol/kg/min, a value not different from zero. NHPkb was 3.1 +/- 0.1 mumol/kg/min and hepatic conversion of leucine to ketone bodies accounted for 3.5% of NHPkb. Insulin deficiency after 3 day's fasting resulted in a near 70% increase in NHPleu (from basal values of 0.31 +/- 0.1 mumol/kg/min to 0.52 +/- 0.06 mumol/kg/min during SAID, p less than 0.01). NHPkb increased from 11.0 +/- 1.0 to 15.5 mumol/kg/min (p less than 0.05). The rate of leucine conversion to ketone bodies (L-C) increased from 1.1 +/- 0.25 to 2.4 +/- 0.3 mumol/kg/min (p less than 0.01) with SAID. We conclude that as the dog progresses to fasting, the contribution of leucine carbon to hepatic production of ketone bodies increases from 3.5% to 10% (p less than 0.01), and this value increases to 15% (p less than 0.01 versus groups I and II) after SAID. Furthermore, the amount of leucine carbon taken up by the liver was not sufficient to account for all [14C]-labeled leucine to ketone bodies. The data suggest that the leucine carbon converted to ketone bodies must have been derived from intrahepatic protein sources of possibly from the keto acids of leucine, which are derived by the breakdown of leucine at distant sites, such as skeletal muscle or adipose tissue. PMID- 2894079 TI - The necrotising vasculitides. PMID- 2894080 TI - Effect of oral terfenadine on the bronchoconstrictor response to inhaled histamine and adenosine 5'-monophosphate in non-atopic asthma. AB - Inhaled adenosine 5'-monophosphate (AMP) causes bronchoconstriction in atopic asthma, probably after in vivo conversion to adenosine. It has been suggested that adenosine potentiates preformed mediator release from mast cells on the mucosal surface of the airways by interacting with specific purinoceptors, without affecting the release of newly generated mediators. The airway response of nine non-atopic subjects with "intrinsic" asthma to inhaled AMP and the influence of the oral, selective H1 histamine receptor antagonist terfenadine on this response was investigated. The geometric mean provocation concentrations of histamine and AMP required to produce a 20% fall in FEV1 (PC20) were 1.82 and 13 mmol/l. In subsequent placebo controlled time course studies the FEV1 response to a single inhalation of the PC20 histamine was ablated after pretreatment with oral terfenadine 180 mg. This dose of terfenadine caused an 80% inhibition of the bronchoconstrictor response to the PC20 AMP when measured as the area under the time course-response curve and compared with the response to PC20 AMP preceded by placebo. Terfenadine 600 mg failed to increase protection against AMP further, but both doses of terfenadine delayed the time at which the mean maximum fall in FEV1 after AMP was achieved. Terfenadine 180 mg had no effect on methacholine induced bronchoconstriction in the same subjects. These data suggest that inhaled AMP may potentiate the release of preformed mediators from preactivated mast cells in the bronchial mucosa of patients with intrinsic asthma. PMID- 2894081 TI - Effects of a cyclo-oxygenase inhibitor, flurbiprofen, and an H1 histamine receptor antagonist, terfenadine, alone and in combination on allergen induced immediate bronchoconstriction in man. AB - The effect of flurbiprofen, a potent cyclo-oxygenase inhibitor, on histamine and methacholine reactivity was assessed in seven atopic subjects with asthma. Flurbiprofen 150 mg daily for three days displaced the histamine-FEV1 concentration-response curve to the right by 1.5 doubling doses, whereas no effect was observed on the response to methacholine. Subsequently the effects of flurbiprofen and terfenadine, a specific H1 histamine receptor antagonist, on allergen induced bronchoconstriction were studied in seven atopic but non asthmatic subjects. The subjects inhaled the concentration of grass pollen allergen that had previously been shown to produce a 20% fall in FEV1 on separate occasions after prior treatment with placebo, flurbiprofen 150 mg daily for three days, terfenadine 180 mg three hours before challenge, and the combination of flurbiprofen and terfenadine. After placebo, allergen challenge caused a mean (SEM) maximum fall in FEV1 of 37.6% (2.6%) after 20 (3.7) minutes, followed by a gradual recovery to within 15% of baseline at 60 minutes. Terfenadine reduced the maximum allergen provoked fall in FEV1 to 21.5% (2.2%) and reduced the area under the time-response curve (AUC) by 50% (6%). Flurbiprofen alone reduced the mean maximum fall in FEV1 to 29.6% (3.2%) and reduced the AUC by 26%. The effect of the combination of flurbiprofen and terfenadine did not differ significantly from that of terfenadine alone. We conclude that histamine and prostaglandins contribute to immediate allergen induced bronchoconstriction and that a complex interaction occurs between the two classes of mediators. PMID- 2894082 TI - Production of antibodies to palytoxin: neutralization of several biological properties of palytoxin. AB - Palytoxin stimulated arachidonic acid metabolism (in bovine aorta endothelial and smooth muscle cells, rat keratinocytes, porcine aorta endothelial cells and rat liver cells), hemolyzed rat erythrocytes and was lethal to mice when administered intraperitoneally. Serum from rabbits immunized with a conjugate in which palytoxin was covalently bound to bovine albumin through its free amino group neutralized these biologic activities of palytoxin. Ninety-nine per cent of the neutralizing activity of the immunized rabbit serum was removed after precipitation of the rabbit IgG with a goat anti-rabbit IgG. PMID- 2894083 TI - [Premedication as a component in the anesthesiological support for radical uranostaphyloplasty in children]. PMID- 2894085 TI - Early lympho-hemopoietic recovery after autografting using peripheral blood stem cells in acute non-lymphoblastic leukemia. PMID- 2894084 TI - Neurohumoral modulation of the pulmonary vasoconstrictor response in the autoperfused working heart-lung preparation during cardiopulmonary preservation. AB - Uncontrolled pulmonary hypertension during autoperfusion of the heart and lungs for preservation has been described, and it may result in extensive pulmonary injury and occasional early failure of the preparation. In order to investigate the neurohumoral mediators of the vasoconstrictor response in the pulmonary circulation of the autoperfused working heart-lung preparation, heart-lung organ blocks were harvested from calves, placed in a normothermic autoperfusion circuit, and studied. Effects of beta-adrenergic stimulation with isoproterenol, nonspecific vasodilatation with nitroglycerin, alpha-adrenergic blockade with phentolamine, phospholipase A2 inhibition with methylprednisolone, cyclooxygenase inhibition with indomethacin, and white blood cell depletion were independently evaluated. Untreated animals, pre- and postexplant, served as controls. Multipoint pulmonary vascular pressure-cardiac output plots were constructed for each animal. An index of pulmonary vascular resistance was obtained from the linear relation: mean pulmonary artery pressure minus pulmonary capillary wedge pressure divided by cardiac output. An intense flow-dependent pulmonary vasoconstrictor response was confirmed to exist in the denervated bovine autoperfused working heart-lung preparation. Isoproterenol afforded better protection against this response than the other agents studied. White blood cell depletion reduced postexplant pulmonary vasoconstriction, implying that circulating polymorphonuclear leukocytes mediate the response in the autoperfused working heart-lung preparation. White blood cell depletion and the administration of selected pharmacologic agents provide modalities for regulating the pulmonary vasoconstrictor response, and thus may enhance lung preservation in the autoperfusion model. PMID- 2894086 TI - Botulinum type D toxin and Clostridium perfringens enterotoxin in a bull calf. PMID- 2894087 TI - Human autoantibodies: probes for nucleolus structure and function. PMID- 2894088 TI - Simultaneous localization of calcitonin mRNA and peptide in a medullary thyroid carcinoma. AB - We report the visualization of calcitonin gene expression products at the mRNA and peptide levels on the same section of a medullary thyroid carcinoma by combined in situ hybridization and immunohistochemistry. mRNA detection was accomplished by hybridization with radioactively labeled antisense RNA probes followed by autoradiography and immunohistochemically using the avidin-biotin complex method. Best results were obtained when in situ hybridization preceded immunohistochemistry, as determined by quantitative analysis of the autoradiographs. When immunohistochemistry was performed prior to in situ hybridization, the RNase inhibitor heparin had to be added to the antibodies to retain hybridizable mRNA. The intensity of the two reactions varied in individual cells, indicating a functional heterogeneity of tumor cells with regard to calcitonin mRNA content and storage of the related immunoreactive peptide. These results, in combination with elevated serum calcitonin levels, suggest significant differences in the rate of secretion of individual tumor cells. Simultaneous localization of mRNA and its peptide within the same cell may, therefore, provide further insight into gene expression and secretory activity at the single cell level. PMID- 2894090 TI - Villin: a cytoskeletal protein and a differentiation marker expressed in some human adenocarcinomas. AB - We studied the expression of villin, a microfilament-associated, actin-binding protein typical of brush-border microvilli, in a variety of human carcinomas by applying immunofluorescence microscopy to frozen sections and immunoblotting methods to tissue extracts using a rabbit antiserum and a monoclonal antibody specific for villin. All of the 24 primary and metastatic colorectal adenocarcinomas tested were uniformly and strongly positive for villin, with the immunocytochemical labeling concentrated at the luminal cell margin. In poorly differentiated tumor areas, rudimentary tubules were stained. All of the six tubular adenocarcinomas of the stomach studied as well as two adenocarcinomas of the gall bladder and a hepatocellular carcinoma were also villin-positive. Villin was detectable in 12 of 14 adenocarcinomas of the pancreas; in some of these cases, its distribution was heterogeneous. Among 21 renal cell carcinomas investigated, positivity for villin was seen in nine of 13 clear cell tumors (especially those of grade II), and in all four chromophilic cell tumors; however, all four chromophobe cell tumors studied were negative. Four of 11 endometrial but none of nine ovarian carcinomas were (uniformly or focally) villin positive. Of 18 adenocarcinomas of the lung studied, one was uniformly and four focally positive for villin, while the remainder were negative. All of the other epithelial tumors studied, including 12 adenocarcinomas of the breast and seven epithelial or biphasic pleural mesotheliomas, were villin negative. Our results show that the expression of villin in intestinal epithelial cells is consistently maintained in their corresponding carcinomas, even when the organized brush-border structure has been lost. The presence of villin in some endometrial and pulmonary adenocarcinomas--in contrast to its absence in the respective normal epithelia--suggests that this protein is newly expressed during hyperplasia, dysplasia, or carcinogenesis. Determining the presence or absence of villin and its immunocytochemical staining pattern in metastatic adenocarcinomas may be of some help in determining the type and site of the primary tumor. PMID- 2894089 TI - Purification and characterization of a growth inhibitory hepatic peptide. A preliminary note. AB - A pentapeptide isolated from normal mouse liver seems to inhibit DNA synthesis (3H-thymidine incorporation into liver DNA and labeling indices) and the mitotic rate (G2-M cell flux) in regenerating mouse liver. The inhibitor is somewhat similar to the growth inhibitory pentapeptides previously reported for granulocytes and epidermis. It is active at very low dose levels, showing a bell shaped dose-response curve. PMID- 2894091 TI - A biochemical and stereological study of neonatal rat hepatocyte subpopulations. Effect of pre- and postnatal exposure to ethanol. AB - Hepatocytes from 12-day-old rats, pre- and post-natally exposed to alcohol, together with those from pair-fed controls, were isolated and subfractionated in six cell subpopulations on Percoll density gradients. These cells were characterized using a combination of biochemical and stereological methods. The low density cells (F2) mainly showed biochemical and stereological features of perivenous hepatocytes, whereas the heavier cells (F6) were primarily periportal hepatocytes. The alcohol-metabolizing enzymes, alcohol dehydrogenase and aldehyde dehydrogenase (high and low Km) showed more activity in the F2 fraction. Alcohol altered mitochondria and Golgi apparatus occurred mainly in F2 cells, whereas the endoplasmic reticulum and lysosomes appeared to be more altered in the F6 hepatocytes. Alcohol also induced the appearance of some small hepatocytes, with a well-developed rough endoplasmic reticulum and an increased number of mitochondria. Biochemical data indicated that glutamate dehydrogenase and alanine aminotransferase were more affected in F2 cells from alcohol-treated rats, and that the activity of the ethanol-metabolizing enzymes was alos reduced in these hepatocytes. Our results indicate that alcohol exposure during zonal development in the liver could have a selective effect on specific cell components depending on the acinar zone, and that the perivenous hepatocytes appear to be more damaged under these conditions. PMID- 2894092 TI - Effects of chronic administration of doxorubicin on myocardial alpha-adrenergic receptors, histamine, cyclic nucleotides, calcium, norepinephrine, calmodulin, and guanylate cyclase activity, and plasma catecholamines in rats. AB - The present study examined changes in the levels of plasma catecholamines and myocardial histamine, guanylate cyclase activity, cyclic nucleotides, calcium, calmodulin, and norepinephrine following chronic administration of doxorubicin (DXR). In addition, changes in myocardial alpha 1-adrenergic receptor density and dissociation constant were measured. Rats received DXR (2 mg/kg) or vehicle weekly by the SC route for 2, 4, 8, and 13 weeks. Rats were sacrificed one week after their last dose. One group of rats treated for 13 weeks was sacrificed at 19 weeks, six weeks after the last dose. Heart histamine was unchanged at 3, 5, 9, and 19 weeks, yet at 14 weeks it was significantly elevated in DXR-treated rats over controls. Cardiac calcium, norepinephrine, and cyclic GMP levels were unchanged throughout the course of the study. Cardiac cAMP and calmodulin levels were unchanged at 3, 5, 9, and 14 weeks. At 19 weeks in DXR-treated rats, cAMP was depressed while calmodulin was elevated. Plasma catecholamines and myocardial guanylate cyclase activity examined at 14 weeks were unchanged. In contrast, alpha 1 receptor density examined at 14 weeks in DXR-treated rats was significantly depressed while the dissociation constant was unchanged. Changes in cAMP and calmodulin are suggestive of a redistribution of calcium, although total levels of calcium were unchanged. The depression of cAMP indicates damage to the membrane bound enzyme, adenylate cyclase, and that the membrane interaction of doxorubicin appears to be an integral part of the biochemical mechanism of its toxicity. PMID- 2894093 TI - Autoradiographic study of 3H-DOPA uptake by superior cervical and stellate ganglia of spontaneously hypertensive rats during the prehypertensive stage. AB - The functional state of sympathetic ganglia in spontaneously hypertensive rats (SHR) was compared with that of ganglia in normotensive Wistar Kyoto rats (WKY) by examining catecholamine synthetic activity by light microscopic autoradiography 3H-L-dihydroxyphenyl alanine (3H-DOPA). The number of silver grains over the perikarya of ganglion cells in the superior cervical (SCG) and stellate ganglia (SG) of newborn, 10-day-old and 30-day-old animals was counted on photographic enlargements. There were significantly more silver grains over ganglion cells in SHR compared with those in age-matched WKY at almost all incorporation times at all ages examined in SCG, at all incorporation times in newborn rats, and at incorporation times of 15 and 60 min in SG of 10-day-old rats. The increased incorporation of the label by both sympathetic ganglia was more marked in newborn than in 30-day-old animals. These results indicate that catecholamine synthetic activity in these ganglion cells is increased in SHR from the newborn stage, suggesting that a congenital hyperfunction of sympathetic ganglia occurs in SHR. PMID- 2894094 TI - [Influence of rations with various linoleic acid contents on the fatty acid composition of phospholipids in blood platelets of rats]. AB - Gas-liquid chromatography was used to study the fatty-acid composition of phospholipids in platelets of Wistar-Kioto rats which received semisynthetic rations with varying content of linoleic acid, 1 week prenatally and 18 weeks postnatally. In ration I the level of 18:2n6 was lower than 0.1 cal%, ration II contained 9.0 cal%, and ration III -- 16.0 cal%. Ration III, as compared to ration II, induced an increase in the content of linoleic fatty acids, arachidonic fatty acid content being unchanged. Ration I, as compared to ration II induced a decrease in linoleic fatty acid content, and an increase in the content of oleic and linolenic fatty acids attended by the appearance of appreciable amounts of 20:3n9 and 20:5n3. Long-term linoleic acid deficiency induced no changes in the unsaturation degree of fatty acids in platelet phospholipids of rats given ration I. This is an evidence of high reserve possibilities of the mechanisms regulating fatty acid metabolism in the mammals. PMID- 2894096 TI - [Alpha-adrenergic control of kidney function. Its significance for the pathogenesis and treatment of arterial hypertension]. PMID- 2894095 TI - [Enzyme parameters in the evaluation of the combined effects of protein deficiency and T-2 mycotoxin]. AB - Male Wistar rats received a low-protein (4.5% protein) diet during 30 days, and T 2-toxin was administered to them through a gastric tube, in a dose of 0.54 mg/kg, during 15 days. The results obtained showed activation of hepatic lysosomal enzymes (sulfatase A and B aryl and beta-glucosidase) and alkaline phosphatase, and to an essential suppression of enzymatic activity of peroxisomes - catalase, glycolate oxidase and D-amino acid oxidase. A sharp aggravation of the intoxication symptoms and pronounced intensification of changes in enzymatic activity in the liver, spleen, thymus and blood serum were recorded in the animals given T-2 toxin simultaneously with the low-protein diet. PMID- 2894097 TI - Induction of plasma and tissue enzymes by drugs: significance in toxicological studies. AB - 1. Observations of drug metabolism enzyme induction in animals during early toxicological trials, and phase I or II of clinical trials, are of importance for the development of a new chemical of pharmacological interest. 2. Induction can be detected by determination of enzyme activities or enzyme proteins in tissues (subcellular fractions or cells in culture). 3. Indirect methods for checking induction can involve determinations of endogenous (i.e. glucaric acid, 6-beta hydroxycortisol) or xenobiotic (antipyrine) metabolites which are produced by the inducible enzyme systems. 4. Recent progress in the knowledge of biochemical mechanisms of induction and the large number of identified isoenzymes in each enzyme 'family' have complicated the interpretation in pharmaco-toxicological studies. 5. This paper describes the present state of the art concerning the relationships between the isoenzymes and the major classes of inducers concerning cytochromes P-450, UDP-glucuronosyltransferases, gamma-glutamyltransferase and epoxide hydrolases. PMID- 2894098 TI - [Astemizole in urticaria--a multicenter study by 412 established dermatologists]. AB - In the course of a multicenter study on 2122 patients treated by 412 dermatologists in general practice, we investigated the effect of astemizole (Hismanal) on urticaria. During 2 weeks of treatment with astemizole 10 mg daily, the percentage of the patients with severe or moderate affection dropped from 82.4% to 9.1%, while the figure of the patients with severe or moderate pruritus decreased from 83.9% to 7.8%. In 74% of the patients, the onset of action occurred during the first 24 hours. The peak of effect was reached within the first day in 36.6% of the patients, and within 2 days in 57.5% of the patients. The physicians observed an excellent outcome in 44.4% and good results in 31.9% of the patients. The therapeutic success was considered moderate in 12.0% and unsatisfactory in 9.6% of the cases. The incidence of side effects was very low, i.e., 5.4%. Slight sedation was observed in 1.9% of the cases. PMID- 2894099 TI - [Multiple forms of tubule alanine aminopeptidase in infants and small children]. PMID- 2894100 TI - [Bivariate differentiation of alcoholic patients based on GGT and ASAT activity in serum]. PMID- 2894101 TI - [Endocrine tumors of the pancreas and duodenum]. PMID- 2894102 TI - Presence of Clostridium perfringens enterotoxin in intestinal samples from farm animals with diarrhoea of unknown origin. PMID- 2894104 TI - [Natural history of ulcero-hemorrhagic rectocolitis. Retrospective study of 120 cases]. PMID- 2894103 TI - Insulin, glucagon and somatostatin secretion by cultured islets from normal and diabetic hamsters. AB - The interhormonal relationship within the pancreatic islets have been studied by previous investigators, but the cellular interplay and the sequence of events in the islet cell's response to stimulators has remained unclear. In the present study, pancreatic islets were isolated by collagenase digestion from normal and streptozotocin-diabetic hamsters the latter being maintained with insulin treatment. The diabetic animals were used to provide A- and B-cell enriched islets. The islets from normal and diabetic hamsters were cultured in medium 199 plus 10% fetal calf serum with 0.8 or 5 mg/ml glucose. The cultures were maintained for up to seven days with medium changes every third day. At specified intervals, media were collected and assayed for insulin, glucagon and somatostatin. Our results showed the expected increased insulin secretion by the B-cells in response to high glucose. However, after two days of culture accumulative insulin secretory response was reduced and at the end of seven days was less than the insulin produced in low glucose medium. Glucagon secretion by the A-cells was similar for low and high glucose media for the entire culture period. Somatostatin secretion by D-cells was stimulated by high glucose but was attenuated after 2 days. No correlation could be found between the concentration of hormone in the media and a possible effect on a specific islet secretion. However, the fact that insulin secretion by islets cultured in high glucose was decreased after two days may indicate a refractoriness produced by persistent hyperglycemia. Islets isolated from diabetic animals secreted more glucagon and less insulin than control islets. Somatostatin secretion was the same in both groups. It was concluded that paracrine relationships were relatively insignificant in the regulation of islet secretion in a prolonged culture environment and persistent high glucose reduced the B-cell response to glucose stimulation. PMID- 2894105 TI - 5-aminosalicylic acid based drugs for the treatment of ulcerative colitis. PMID- 2894106 TI - The influence of alfentanil on the intubating conditions after priming with vecuronium. AB - The ability of alfentanil 15 micrograms kg-1 or 30 micrograms kg-1 to improve intubating conditions was studied in four groups of 25 ASA class 1 patients. Induction of anaesthesia was with thiopentone 5 mg kg-1. Neuromuscular blockade was induced with vecuronium using the priming principle. The priming dose, priming interval and intubating dose were 0.01 mg kg-1, 4 min, and 0.1 mg kg-1, respectively. Intubation was attempted 1 min after the intubating dose. Intubating conditions were judged unacceptable in about 30% of the patients belonging to the control groups. Alfentanil 15 micrograms kg-1, when administered 65 s before intubation, reduced the incidence of coughing and diaphragmatic movement (P less than 0.05) but did not reduce the incidence of overall unacceptable intubating conditions. Alfentanil 30 micrograms kg-1, however, reduced the incidence of vocal cord movement (P less than 0.005) as well as coughing and diaphragmatic movement (P less than 0.002). Alfentanil 30 micrograms kg-1 reduced the incidence of unacceptable intubating conditions from about 30% to 4% (P less than 0.02). PMID- 2894107 TI - Diffusion of metronidazole through the dentinal tubules of extracted teeth. AB - Passing of metronidazole from the root canal of extracted gangrenous teeth through the dentinal tubules was proved by agar diffusion and minimum inhibitory concentration assay. The findings explain the excellent clinical experience with metronidazole in root treatment. PMID- 2894108 TI - The specificity of antisera against Bordetella pertussis examined by bacterial agglutination. AB - The specificity of conventional, adsorbed antisera against agglutinogens 1, 2, and 3 of Bordetella pertussis was examined by slide agglutination and by agglutination in microtitre wells. Unadsorbed hyperimmune sera showed higher agglutinating activity against autologous or homologous cells than against cells of heterologous serotype. Adsorption of sera with heterologous cells increased the serotype specificity considerably. In spite of extensive adsorption, these anti-agglutinogen sera were still found to cross-react with B. parapertussis and/or B. bronchiseptica strains. Adsorption experiments with B. pertussis hyperimmune sera against serotype 1-, 1.2-, and 1.3-organisms demonstrated that the cross-reacting surface antigens differed from the agglutinogens 1, 2, and 3. Thus, in making species-specific reagents for diagnostic use it may be of value to include adsorption with B. parapertussis and probably with B. bronchiseptica. Limited data indicated that there is no need to use B. avium for adsorption. The agglutination assays were also used to test three monoclonal antibodies stated to be specific for the agglutinogens 1, 2, and 3, respectively. Some anomalous behaviour for the anti-agglutinogen 1 reagent was found, whereas the anti agglutinogen 2 and 3 reagents corresponded well with the present polyclonal factor sera. PMID- 2894109 TI - Oxidation of beta-blocking agents. V. Light-influenced oxidation of propranolol and its glycol with N-bromosuccinimide. PMID- 2894110 TI - Effect of clotiazepam on gastric mucosal lesions produced by conditioned emotional stimuli in mice. AB - The anti-ulcer action of clotiazepam (a thienodiazepine derivative) was studied in mice subjected to non-physical and physical stimuli in a communication box. There were two groups of mice: the "sender" mice that received electric shocks on the feet and responded by squealing and jumping, and the "responder" mice that were affected by the senders' responses without receiving shocks on the feet. Gastric ulcers resulted in both groups. The effect of clotiazepam was compared with that of diazepam. The incidence of gastric ulcers was suppressed by clotiazepam at a dose of 3 mg/kg, per os, in "responder" and "sender" mice, and by diazepam at a dose of 1 mg/kg, per os, in "responder" mice. These results suggest that clotiazepam has a suppressive action against gastric ulcers produced by non-physical or physical stimuli, although its potency is slightly weaker than that of diazepam. PMID- 2894111 TI - [Participation of Bacillus thuringiensis subsp. israelensis plasmids in the determination of crystal endotoxin synthesis]. PMID- 2894112 TI - Isolation, purification and identification of antibiotic complex-1011 from Streptomyces sp. 1011. PMID- 2894113 TI - Comparative investigation of the components of antibiotic complex 1011 with thin layer chromatography of variants from Streptomyces sp. 1000. PMID- 2894115 TI - [Integral therapy of complex joint injuries]. AB - The final treatment result in severe joint injuries especially in polytraumatized patients, after a correct primary care, depends on a logical sequence of application of all necessary supporting measures. The importance of these special steps depending on the overall type of injury should preferably be assessed and controlled by the surgeon who performed the initial treatment. Several examples of an integral treatment of different joint injuries are demonstrated. PMID- 2894114 TI - Molecular biological studies on structure and mechanism of proton translocating ATPase (H+-ATPase, F0F1). AB - Recent results on ATPase, mainly from E. coli, obtained by biochemical and molecular biological approaches are reviewed, with special emphasis on results obtained in this laboratory. The advantages of using E. coli in studies of this important enzyme in oxidative phosphorylation are indicated: variant enzymes with specific amino acid replacements can be obtained and their functions and structures can be compared with those of the wild-type enzyme. Structural aspects of this complex enzyme are discussed, including the primary amino acid sequences and molecular assembly of subunits, and mechanistic aspects of the catalytic mechanism and proton translocation. PMID- 2894116 TI - [Arthrolysis in the treatment of post-traumatic joint stiffness of the knee and elbow joints]. AB - In the treatment of posttraumatic limitation of the range of motion, arthrolysis is a proved procedure in the hand of an experienced surgeon. In this paper, indication, operative details and postoperative treatment are discussed. The results of 51 cases of arthrolysis of the knee joint and 33 cases of arthrolysis of the elbow joint carried out over a time of seven years are reported. PMID- 2894117 TI - [Synergistic joint diagnosis]. AB - Many methods are useful in the diagnosis of diseases of the joints. Noninvasive methods deserve preference; invasive techniques such as arthrography and arthroscopy are second choice, after noninvasive methods have been applied. The synergic combination of the two last-named methods has proved successful. Arthrography, performed before arthroscopy in the operation theatre, supplements arthroscopy findings and extends the diagnostic value of the arthroscopic findings, in a similar manner as the combination of computed tomography and arthrography. PMID- 2894118 TI - [Development of intramedullary nailing and the interlocking nail]. AB - Development of practically feasible methods for intramedullary stabilisation of fragments is inseparably linked to the name of Gerhard Kuntscher. The principle of elastic transverse fixation of the nail in the medullary cavity permits its use only in fractures in the median diaphyseal range of tubular bones. For multiple and comminuted fractures Kuntscher recommended a so-called "detention" or "locking" nail. This was developed further by Klemm and Schellmann, thus extending the range of indication for intramedullary fragment stabilisation. The origins and phases of development of this method are shown. PMID- 2894119 TI - [Expert assessment of reduced earning capacity in legal accident insurance following traumatic loss of the spleen]. AB - For legally binding assessment of reduced earning capacity after loss of spleen in adolescents and adults--in accordance with the Federal German compulsory accident insurance regulations--the article offers a brief review of expertising practice and then proceeds to examine dogmatically which of the cases of subsequent damage after loss of spleen are relevant according to German social security laws. The risk covered by Federal German compulsory accident insurance is critically discussed while bearing in mind that assessment of reduced earning capacity is done exclusively under the viewpoint of objectifiable functional losses. PMID- 2894120 TI - [Reconstruction of tangential and circular infected bone defects]. AB - In the treatment of bone infections the reconstruction and rehabilitation of bone defects is a problem that often requires treatment secondary to curative treatment of the infection. For the reconstruction of smaller and more extensive defects we used predominantly (92.7%) autogenous (autologous) untreated spongiosa and in only 7% of the cases allogenic (homologous) spongiosa from an organ bank, this being added if necessary. Recently the additionally introduced vascularized bone chip has become a useful extension of the therapy concept. The problems and complications of defect reconstruction are demonstrated for 705 cases of bone infection with 472 defects of different sizes, based on a comprehensive classification with defect calculation. Surgical technical approach and special aspects of after-treatment are described, as well as the results for every group of cases. We achieved stability and freedom from infection in a total of 93.7% of the patients. As was to be expected, the problems grow with the size of the defect. Particularly problematic are joint infections with adjacent extensive circular defect. PMID- 2894121 TI - [Contusion of the heart]. AB - Whereas heart contusion can be identified by autopsy as a traumatic damage to the heart, clinical diagnosis during life is mostly made by exclusion only and subsequently, the more so since there is no absolutely reliable parameter that permits diagnosis ad hoc. Complications often develop only hours or days after the accident. Heart contusion can be masked by haemorrhagic-traumatic shock and accompanying injuries and delay its diagnosis. Traumatic damage to the myocardium can equal a myocardial infarction. Hence, it is imperative that persons injured in an accident who are suspected of having suffered a contusion of the heart, are placed in an intensive-care ward to recognise complications well in time and to institute therapeutic measures without delay. As is the case with acute myocardial infarction, anaesthesia and surgery can be performed only in case of a vital indication. PMID- 2894122 TI - [Closed femoral intramedullary nailing without drilling--a 14-year evaluation]. AB - A sufficiently stable osteosynthesis is demanded on the basis of the conditions formulated for the healing of bone fractures. This demand applies to fractures in general. For intramedullary nailing in particular, it is a major postulate that sufficient stability can only be attained if the medullar cavity is drilled open. Such drilling aims at establishing an extended contact between the cortical substance of the bone and the nail while exercising at the same time a clamping force that is elastic in transverse direction. In our accident emergency hospital (Ludwigshafen) the medullar cavity is not drilled open. This entails the use of frequently very thin intramedullary nails so that the nail can pass through the hourglass-like narrow pathway in the centre. Although this kind of osteosyntheses is insufficient in respect of stability and ensuring rotation, the healing of bone fractures does not present any problems. As a matter of fact, 450 femurs have been treated at our hospital during the pase 14 years with intramedullary Kuntscher nailing without drilling. It is demonstrated that this kind of stabilising the fracture is associated with an extremely low incidence of pseudarthroses and infections. Further complications are stated. PMID- 2894123 TI - [Conservative therapy of acetabular fractures--indications and results]. AB - Conservative treatment of acetabular fractures seems to be indicated either in cases of little displacement or wherever reconstruction of the acetabulum by operation is impossible. Following the classification of Judet and Letournel a satisfactory result can be expected only in fractures with little dislocation, such as the caudal transverse type and the anterior wall type. The indication for open reduction and reconstruction is given if cranial and/or dorsal components of the acetabulum are involved. In special cases treatment by vertical traction must be combined with a side traction by means of a trochanter screw; in the early phase of traction frequent radiological controls are obligatory. Early physiotherapy is also necessary to achieve satisfactory functional results. Based on the follow-up examination of 38 patients with 39 fractures of the acetabulum, conservative treatment is discussed in respect of fracture type, the extent of displacement and the clinical results. PMID- 2894125 TI - Differential diagnosis of facial chorea. PMID- 2894124 TI - Epidemiology and pathophysiology of tardive dyskinesias. PMID- 2894126 TI - Involuntary vocalizations in movement disorders. PMID- 2894127 TI - Adaptive changes in brain dopamine function as a result of neuroleptic treatment. PMID- 2894128 TI - Dopaminergic mechanisms in cranial dystonia. PMID- 2894129 TI - Use of monoclonal antibodies for the differential detection of Trypanosoma cruzi and T. rangeli in epidemiological studies and xenodiagnosis. AB - T. cruzi and T. rangeli have the same insect and mammalian hosts, including man, and in addition share approximately half the antigenic determinants recognised by the humoral response. Thus serodiagnosis of T. cruzi infection in areas where T. rangeli is endemic may include an unknown rate of false positives due to this antigenic cross-reactivity. Similarly, the results of xenodiagnostic procedures and epidemiological surveys of insect vectors are prone to distortion because of the close morphological resemblance of the epimastigote stages. The description of a T. cruzi epimastigote specific monoclonal antibody, 2A2, which reacts with both culture and insect derived epimastigotes provides a more reliable basis for differential diagnosis of these two parasites. PMID- 2894130 TI - Electron microscopical studies on cutaneous leishmaniasis in Ethiopia. II. Parasite and host cell differences between the localized and the diffuse form. AB - The ultrastructure of Leishmania aethiopica parasites and their host cells was investigated in lesions of 7 patients suffering from diffuse cutaneous leishmaniasis (DCL) and in lesions of 4 patients with localized cutaneous leishmaniasis (LCL). The appearance of host cells and parasites varied considerably in both disease forms. Host cell variations occurred especially in the number of cytoplasmic vesicles, the size of the parasitophorous vacuoles, and the number of amastigotes per parasitophorous vacuole. Differences concerned the occurrence of a special macrophage-type in DCL-lesions which was characterized by an electron-translucent cytoplasm and a low degree of parasitization, larger parasitophorous vacuoles with higher numbers of amastigotes per vacuole in infected macrophages from DCL-patients, and the number of electron dense granules in host cell vacuoles of DCL-patients. The parasites inducing DCL and LCL significantly differed in size and membrane structure: Amastigotes had a length of 2.27 +/- 0.48 micron and a width of 1.77 +/- 0.40 micron in DCL-lesions, and 1.92 +/- 0.40 micron and 1.48 +/- 0.32 micron in LCL-lesions. Promastigotes obtained from DCL-patients revealed 2078 +/- 308 integral membrane particles (IMP)/micron2 and 892 +/- 246 IMP/micron2 on the P- and E-fracture faces of plasma membranes, while the corresponding values of LCL-derived promastigotes amounted to 1690 +/- 376 IMP/micron2 and 652 +/- 274 IMP/micron2, respectively. PMID- 2894131 TI - Comparative infectivity of a Kenyan strain of Leishmania donovani amastigotes for Rattus rattus and the laboratory white rat. AB - Amastigotes of a Kenyan strain of Leishmania donovani from a previously infected hamster were used to inoculate Rattus rattus and the laboratory white rat intracardially. The animals were sampled at 2, 4, 6, and 12 weeks post inoculation to determine infectivity and total parasite burdens in the liver and spleen. Higher parasite burdens were observed in the livers and spleens of R. rattus. Parasite culture indicated more generalized parasite dissemination compared to the white rat. Demonstration of the parasite in dermal tissue of R. rattus at 2 and 4 weeks suggests that the parasite may be accessible to sandfly vectors. Transient susceptibility to systemic infection and parasite survival in dermal tissue suggests a potential role of R. rattus in the transmission cycle of Kenyan visceral leishmaniasis. PMID- 2894132 TI - Compliance with malaria chemoprophylaxis programmes in Zimbabwe. AB - Compliance with malaria chemoprophylaxis programmes was studied in the National Railways and two large commercial farm labour forces in Zimbabwe. Prophylaxis was primarily conducted using pyrimethamine/dapsone and the study measured compliance rates through interview and the detection of drug in the urine. Compliance rates as indicated from registers or questioning were not always reliable and were found from urine examination to be in the range of 50-60% for the farm labour force. Annual drug utilization figures also indicated that complete coverage was not being achieved. - The results are discussed in relation to the difficulties involved in implementing malaria prophylaxis programmes. The limited use of large scale chemoprophylaxis is stressed, particularly in the light of increasing drug resistance. PMID- 2894133 TI - Seasonal patterns in the transmission of Schistosoma haematobium, S. mattheei and S. mansoni in the highveld region of Zimbabwe. AB - The pattern of fluctuation in the population size of Bulinus globosus and Biomphalaria pfeifferi, in their infection rates with Schistosoma haematobium/S. mattheei and S. mansoni, respectively, and in the cercarial population size as monitored using hamster immersions, was elucidated in streams in the temperate highveld region of Zimbabwe over a 27-month period during 1982-1984. The results revealed that transmission of S. mansoni was erratic and unpredictable without a clearcut seasonal transmission pattern. In contrast, transmission of S. haematobium and S. mattheei exhibited a marked seasonal pattern, being most intensive during the hot, dry season (September-November) and markedly reduced during the cold, dry season (June-August). During the rainy (December-February) and warm, post-rainy (March-May) seasons transmission was moderate and variable, but occasionally intensive. The results also showed that rodent immersion is to be preferred to measurements of snail population size and snail infection rate in elucidating seasonality of transmission of schistosomiasis. PMID- 2894134 TI - Population dynamics of Onchocerca volvulus after 7 to 8 years of vector control in West Africa. AB - In an attempt to describe the changing population dynamics of Onchocerca volvulus during a period of vector control, nodulectomies were undertaken in 256 patients from ten villages in the Onchocerciasis Control Programme (OCP) and in 74 patients from two villages in an area with ongoing transmission. A total of 1198 nodules were excised and 4350 adult worms were isolated and examined for viability and productivity. In the OCP villages, the worm population is ageing and dying without replacement by new generations of parasites and various findings signal a breakdown of the worm population after about 12 years interruption of transmission. The sexual activity of the worms was significantly reduced. A Productivity Index was developed to measure the microfilariae production at the nodule level. The reduction in this index for the OCP villages correlates closely with the decline over the control period in the community microfilarial loads in the skin. The results show that it is not only the longevity of the parasite which will determine the duration of vector control, but that the reduced productivity of the ageing parasite population is of equal importance. PMID- 2894135 TI - Serodiagnosis of African trypanosomiasis using a chemiluminescent enzyme immunoassay. PMID- 2894136 TI - Competent metabolic utilization of hydrogen peroxide by trypanosomes. PMID- 2894137 TI - Diabetogenic action of calcitonin in acute experiment in healthy humans. PMID- 2894138 TI - Virion transcriptase activity of rimantadine-sensitive and rimantadine-resistant variants of human influenza virus. AB - All rimantadine-resistant variants of influenza virus prepared by consecutive passages in the presence of rimantadine had increased virion transcriptase activity as compared to the original strains. The increased virion transcriptase activity of rimantadine-resistant strains was unrelated to the possible role of M1 protein, since RNPs isolated from the virions of these variants also revealed higher transcriptase activity as compared to RNPs isolated from rimantadine sensitive virus. The study of rimantadine-resistant recombinant X-4 which inherited from the resistant fowl plague virus (FPV) only the gene 7 coding for M proteins provided additional evidence for the suggestion that the increased virion transcriptase activity of rimantadine-resistant influenza virus variants is coincidental rather than directly associated with such resistance. PMID- 2894139 TI - Potiskum virus: enhancement of replication in a macrophage-like cell line. AB - Replication of Potiskum virus was studied in P388D1 macrophage-like cell line in the presence and absence of subneutralizing concentrations of specific antiviral antibody. The cultures were infected at multiplicities of infection (MOI) ranging from 0.4 to 0.0004. The virus replicated to high titres at all MOI tested, but there was an enhancement of virus replication in cultures supplemented with the antibody. Enhancement of replication was MOI dependent, the highest ratios being obtained in cultures infected at lowest MOI. In enhancement assays using various dilutions of immune mouse ascitic fluid (IMAF), the highest enhancement ratio was observed at dilution 1 : 500; the enhancing antibody titre was 5,000. PMID- 2894140 TI - An enzyme-linked immunosorbent assay (ELISA) for measurement of antibodies against equine herpesvirus 2 in equine sera. AB - An indirect enzyme-linked immunosorbent assay (ELISA) was developed for the detection of antibodies against equine herpesvirus type 2 (EHV-2) in equine sera. The optimal conditions of antigen concentration, and serum and conjugate dilutions were established by chequerboard titrations. When the standard ELISA test was used for titration of test sera, it was found to give titres approximately 1500 times higher than those obtained in the virus neutralization (VN) test, and a correlation coefficient of 0.815 was obtained between these two tests on 42 equine sera. All the positive serum samples by the VN were also positive by the ELISA, and one negative serum in the former test was found to be positive in the latter. Under field conditions, the test also detected increases in antibody titres against EHV-2 in 13 out of 14 foals soon after these animals excreted the virus. PMID- 2894141 TI - Preparation of influenza B virus recombinant strains. AB - The study of antigenic and biologic properties of influenza B epidemic viruses isolated in 1979 and 1983 and laboratory strain B/Lee/40 has revealed some differences in their biologic properties. The most marked changes have been found in the haemagglutinin (HA) and neuraminidase (NA) indicating that influenza B viruses underwent dramatic antigenic drifts during the period in question. The strains obtained by genetic recombination have inherited surface antigens of epidemic influenza B/Singapore/222/79 and B/USSR/100/83 viruses and preserved the HA thermolability inherent to these viruses. They have, however, acquired the marker of reproduction in chick embryos and the immunogenicity from the donor strain B/Lee/40. These recombinants can be, therefore, recommended as vaccine strain candidates. PMID- 2894142 TI - Formation of autoimmune effectors after transfer of virus-induced autoreactive precursors to syngeneic intact receptor animals. AB - We verified the assumption that autoimmune responses underlie immunosuppression developing in the course of virus infection. It has been shown by adoptive transfer that administration of Langat-virus-induced autoreactive lymphocytes (ARL) to the syngeneic recipient is followed by accumulation of autoreactive effectors (AE) eliciting a graft-verus-host reaction (GVHR) in the syngeneic system (AEgvhr). In addition, cytotoxic T-lymphocytes (AEc) appeared against the syngeneic macrophages. This effect was mediated by the H-2 restriction principle for ARL donors and their recipients. The infection triggered a T-suppressor mediated reaction inhibiting the differentiation of precursors into mature autoreactive effectors. In the absence of T-cell suppressor effect (on consecutive syngeneic transfer) ARL will cause systemic pathologic changes in the recipients, namely, infiltrative and necrotic lesions in different organs and tissues. This mechanism is attributed to the activation of precursors in the body of intact recipient and to the formation of mature effectors owing to cytokines released by donor ARL. PMID- 2894143 TI - Barbash strain spotted fever group rickettsia is a strain of Rickettsia conorii and differs from Rickettsia sibirica. AB - The Barbash strain of spotted fever group rickettsia was reexamined in this study by the microimmunofluorescence test with mouse antisera and with monoclonal antibodies. Protein immunoblotting was performed for comparison of purified antigens of R. rickettsii, R. sibirica, R. conorii and Barbash strain. Comparison of Barbash strain, R. rickettsii (Sheila Smith strain), R. conorii (Malish 7 strain), and R. sibirica (strains 232, 246 and Jinghe-74) of the spotted fever group in the microimmunofluorescence test of Philip et al. revealed that Barbash strain has antigens that yield homologous titers with the R. conorii strains and differ from R. sibirica and R. rickettsii. Monoclonal antibodies specific for R. conorii react at identical titres with the Barbash strain, and a monoclonal antibody specific for R. sibirica does not react with the Barbash strain. Likewise, T-cell hybridomas reactive with R. conorii but not R. sibirica yield a strong response when stimulated by Barbash strain antigens. Western immunoblotting with the same polyclonal and monoclonal antibodies confirmed the presence of specific protein antigens of R. conorii and different protein antigenic composition of R. sibirica when compared with Barbash strain. Thus, Barbash strain is a strain of R. conorii. PMID- 2894144 TI - Effect of Mg2+ ions on the in vitro translation of red clover mottle virus M RNA. AB - Red clover mottle virus middle-component RNA was translated in rabbit reticulocyte lysate into two primary polypeptides with molecular weights of 95,000 and 105,000. The relative ratio of the two polypeptides synthesized was affected by Mg2+ concentration. PMID- 2894145 TI - Serological evidence of the distribution of murine alphaherpesviruses on the territory of Czechoslovakia. PMID- 2894146 TI - Respiratory complications of gastroesophageal reflux. AB - Gastroesophageal reflux may predispose patients to pulmonary complications such as bronchospasm and aspiration pneumonitis. This is especially true in patients who are critically ill, those with reflux-induced asthma and those undergoing general anesthesia. Decreasing the amount of acid reflux reduces the potential for respiratory complications. In patients at risk, administration of H2-receptor antagonists minimizes the risk of acid aspiration and resolves asthma symptoms. PMID- 2894147 TI - Drug therapy for intracranial suppuration. PMID- 2894149 TI - A symposium: Rilmenidine--a novel alpha2 agonist antihypertensive agent. PMID- 2894148 TI - Hemodynamic recovery during simulated ventricular tachycardia: role of adrenergic receptor activation. AB - Ventricular tachycardia (VT) produces a wide variety of hemodynamic outcomes. Variations in autonomic nervous system response were studied in an animal model of VT. In 18 dogs anesthetized with chloralose VT was simulated by ventricular pacing (rate 240 bpm). Dynamic changes in left ventricular (LV) function were assessed during sinus rhythm and after VT was initiated, under variable autonomic conditions: ganglionic blockade with hexamethonium (n = 5), alpha-adrenergic blockade with terazosin (n = 7; 0.3 mg/kg), and beta-adrenergic blockade with propranolol (n = 6; 2 mg/kg). Micromanometers were used to measure LV pressure, and endocardial piezo crystals assessed changes in cavity size. Sinus interval, an index of autonomic tone, was determined immediately after tachycardia was terminated. Under control conditions the onset of simulated VT was accompanied by severe hypotension, with a decline in LV systolic pressure from 113 +/- 5 to 67 +/- 4 mm Hg within 10 seconds (p less than 0.05). Subsequently, during persistent tachycardia peak LV pressure recovered to sinus values, and maximum +dP/dt exceeded sinus values by 20 seconds (2604 +/- 413 vs 2112 +/- 184 mm Hg/sec; 20 seconds for VT vs sinus rhythm). Diastolic pressures were unchanged, and sinus rate accelerated. Ganglionic blockade with hexamethonium resulted in persistent hypotension, blunted +dP/dt, no change in diastolic pressures, and failure of the sinus rate to accelerate after the tachycardia. After beta blockade there was sustained hypotension (LV systolic pressure 78 +/- 4 vs 120 +/- 5 mm Hg; 20 seconds for VT vs sinus rhythm), maximum +dP/dt was blunted, and minimum diastolic ventricular pressure rose. This was due to an upward shift in the diastolic pressure-dimension relationship associated with prolongation of the time constant of LV relaxation. The sinus interval did not change. In contrast, tachycardia during alpha blockade produced a sustained fall in peak LV pressure; however, maximum +dP/dt recovered (2194 +/- 328 vs 2154 +/- 153 mm Hg/sec; 20 seconds for VT vs sinus rhythm), minimum diastolic LV pressure remained low, and sinus rate accelerated after ventricular tachycardia. Hemodynamic recovery during ventricular tachycardia is mediated by the response of the autonomic nervous system and requires both alpha-adrenergic vasoconstriction and beta-adrenergic augmentation of contraction and relaxation. PMID- 2894150 TI - Advantages and disadvantages of alpha 2-adrenoceptor agonists for systemic hypertension. AB - Alpha 2-receptor agonists are effective antihypertensive drugs that reduce sympathetic activity by both central and peripheral mechanisms. Plasma noradrenaline and renin concentrations are reduced. Hemodynamic disturbances are minor with a near-normal cardiovascular response to standing, exercise and volume depletion. The main problems are due to central adverse effects, particularly sedation, and a syndrome of sympathetic overactivity on sudden withdrawal. These problems can be minimized by using lower doses, while therapy with a useful antihypertensive drug is maintained. Clonidine and its analogs have a low toxicity and very few contraindications. They remain a useful part of the therapeutic armamentarium in hypertension. PMID- 2894151 TI - Sites of actions of alpha 2 agonists in the brain and periphery. AB - Alpha 2 agonists including rilmenidine, clonidine and alpha methylnoradrenaline all seem to have a predominantly central action in lowering blood pressure. Studies using the peripheral decarboxylase inhibitor alpha-methyldopa hydrazine in both experimental animals and humans support the predominant central action of the active metabolite of methyldopa, alpha methylnoradrenaline. Comparative studies on the antihypertensive potency of selective alpha 2 agonists like rilmenidine, guanfacine, clonidine and lofexidine suggest that the relative ability to bind to alpha 1 and alpha 2 adrenoceptors is not critical but the ability to enter the central nervous system is essential for antihypertensive efficacy. PMID- 2894152 TI - Sites of action of alpha 2 agonists and antagonists. AB - The alpha 2 adrenoceptor is found on central and peripheral neurons, on vascular smooth muscle and on endocrine tissue. Although some investigational drugs have widely varying affinities for these sites, clinically available alpha 2 agonists and antagonists act at all alpha 2 receptors. This report illustrates a strategy for evaluating the relative contributions of both central nervous system vs peripheral and of prejunctional vs postjunctional actions of a new drug by measurement of several alpha 2 receptor-mediated hemodynamic and neuroendocrine responses. Evidence is also provided for a temporal dissociation of pre- and postjunctional alpha 2 responses that may permit selective postjunctional alpha 2 blockade to be of clinical value in the treatment of sympathetically induced reductions of skin blood flow. PMID- 2894153 TI - Cardiovascular and central nervous system effects of rilmenidine (S 3341) in rats. AB - Rilmenidine (S 3341) is a new alpha 2 agonist, with antihypertensive properties. Pharmacologic data concerning its hemodynamic and central nervous system effects in the rat are described in this report. In the anesthetized or conscious spontaneously hypertensive rat, rilmenidine was found effective and potent as an antihypertensive agent, lowering blood pressure in a dose-dependent manner after intravenous and oral administration. These effects are related to a reduction in sympathetic tone as seen by the decrease in plasma catecholamines induced by rilmenidine in the spontaneously hypertensive rat. Studies in the normotensive pithed rat (electrical stimulation and adrenalectomization) confirmed the presynaptic alpha 2-stimulating properties of rilmenidine and suggested that a component of the antihypertensive activity of rilmenidine could be exerted through these peripheral receptors. A study of the central effects of rilmenidine was performed using classic neuropharmacologic tests. No effect was observed on the pentobarbitone-induced sleeping time in the rat. Rilmenidine caused only a minimal and non-dose-dependent inhibition of the righting reflex in the chick. In the rat, rilmenidine did not decrease the motor activity at concentrations up to 50 times higher than the antihypertensive dose. These results confirmed the contrast between rilmenidine and clonidine and suggest that a dissociation between sedative and antihypertensive effects could occur with rilmenidine. PMID- 2894154 TI - Action of rilmenidine on locus ceruleus and dorsal raphe cells in vivo and in vitro. AB - The effect of rilmenidine (S 3341) and clonidine on the firing rate of locus ceruleus (LC) and dorsal raphe (DR) cells was studied in vivo after systemic and microiontophoretic administration. The effect of the 2 drugs was also studied in vitro on brain slices containing LC cells. Rilmenidine and clonidine inhibited the firing of LC and DR neurons. Complementary experiments performed with yohimbine and prazosin demonstrated that the effect of LC is related to an agonistic action on alpha 2 somatodendritic receptors, whereas the effect observed on DR cells is indirect. On LC cells, clonidine is 30 to 60 times as potent as rilmenidine. These observations may be related to less sedative effects of rilmenidine than of clonidine. PMID- 2894155 TI - Effects of two alpha 2 agonists, rilmenidine and clonidine, on the morphine withdrawal syndrome and their potential addictive properties in rats. AB - The interaction between adrenergic systems and opiate receptors or neuronal systems linked to these receptors has been previously demonstrated. For this reason, clonidine can be used to reduce withdrawal syndrome to opiates. Rilmenidine (S 3341) is a new agonist of alpha 2 adrenoceptors. The purpose of these experiments was to compare the effects of rilmenidine and clonidine on morphine withdrawal syndrome and their potential addictive properties in the rat. Rats were made morphine-dependent by repeated intraperitoneal (i.p.) administration of increasing doses of morphine. Withdrawal was precipitated by injecting naloxone subcutaneously. Withdrawal scores were evaluated for 10 minutes. Clonidine (0.05, 0.1 and 0.2 mg/kg, i.p.) and rilmenidine (5 and 10 mg/kg, i.p.) significantly reduced overall withdrawal scores. Addictive potential was evaluated in the rat by a place preference test after the following treatments (mg/kg, i.p.): rilmenidine 0.1 to 5, clonidine 0.01 to 0.5, heroin 0.12, and d-amphetamine 1.5. Rilmenidine did not modify the time spent in the conditioned side at doses of 0.1 to 1 and 5 mg/kg, but increased it at 2.5 mg/kg (+25%). In contrast, a reinforcing effect was induced by clonidine (+21%, +43%, +34% at 0.1, 0.25, 0.5 mg/kg), heroin (+39%) and amphetamine (+52%). In conclusion, rilmenidine as well as clonidine reduced the morphine withdrawal syndrome. However, rilmenidine was 100 times less active than clonidine. Clonidine, heroin and d-amphetamine have clear reinforcing properties. Rilmenidine did not exhibit dose-dependent reinforcing properties and the isolated effect noted after 2.5 mg/kg is difficult to interpret because it is minor and is not observed with a higher dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894156 TI - Effects of continuous infusions (10 days) and cessation of infusions of clonidine and rilmenidine (S 3341) on cardiovascular and behavioral parameters of spontaneously hypertensive rats. AB - Clonidine is a centrally acting antihypertensive drug that acts in vivo at both alpha 1- and alpha 2-adrenoceptor sites, whereas rilmenidine (S 3341) is more selective for alpha 2 adrenoceptors. The present study compared the effects of continuous 10-day infusions of clonidine (5 micrograms/kg/hour) with those of rilmenidine (100 micrograms/kg/hour) on various cardiovascular and behavioral parameters in the spontaneously hypertensive rat. The changes in these parameters after cessation of the infusions were also compared. At these rates of infusion, clonidine and rilmenidine produced quantitatively similar reductions in mean arterial pressure (MAP), lability of MAP and cardiovascular responsiveness during normal behaviors such as eating and grooming. Neither drug infusion affected heart rate. The cessation of the clonidine infusion resulted in a "withdrawal" syndrome characterized by prominent rapid eye movement-sleep rebound, and cardiovascular and behavioral disturbances including an increased lability of MAP, exaggerated cardiovascular responses during normal behaviors, tachycardia, and an "opiate abstinence-like" syndrome including head and body shakes. Cessation of rilmenidine infusion resulted in somewhat similar cardiovascular and behavioral disturbances, but unlike clonidine there was a return to normal rapid eye movement sleep without rebound. PMID- 2894157 TI - Effects of rilmenidine on bronchomotor responses in the guinea pig. AB - This study compares the effects of 2 alpha 2-adrenergic agonists, rilmenidine (S 3341) and clonidine, on histamine-induced bronchoconstriction (HIB) in guinea pigs. Clonidine has previously been shown to potentiate HIB in guinea pigs. The study was conducted in anesthetized, paralyzed and ventilated guinea pigs. Six groups of at least 6 guinea pigs were pretreated with saline, rilmenidine (0.1, 0.3 and 1 mg/kg intravenously) or clonidine (0.01 and 0.03 mg/kg intravenously), respectively. Conductance, dynamic compliance and static compliance of the respiratory system were measured before and during histamine infusion (80 ng/kg/s) and expressed as percent variation. Clonidine potentiated HIB as previously reported. In contrast, rilmenidine potentiated HIB only at the dose of 1 mg/kg. As it is well known that HIB is influenced by adrenergic outflow, these results suggest that rilmenidine has less inhibitory effect than clonidine on adrenal secretion. PMID- 2894158 TI - Pharmacokinetics of rilmenidine in healthy subjects. AB - Rilmenidine is a novel alpha 2-adrenoceptor agonist, used in the treatment of mild or moderate hypertension at the oral dose of 1 mg once or twice daily. The pharmacokinetic parameters were investigated after single or repeated administration in healthy subjects, using labeled and unlabeled compounds. Rilmenidine was rapidly and extensively absorbed, with an absolute bioavailability factor close to 1 and a maximal plasma concentration achieved within 2 hours. Rilmenidine was not subject to presystemic metabolism. Distribution was independent of the free fraction because rilmenidine was weakly bound to plasma proteins (less than 10%). The volume of distribution was approximately 5 l.kg-1 (315 liters). Elimination was rapid with a total body plasma clearance of approximately 450 ml.min-1 and an elimination half-life of approximately 8 hours. Renal excretion was the major elimination process (two thirds of the total clearance). Metabolism was very poor, with a renal elimination of rilmenidine as the parent drug (urinary fraction of rilmenidine was about 65% and no metabolite plasma levels were detected). Linear pharmacokinetics were demonstrated for rilmenidine from 0.5 to 2 mg but, at 3 mg, a slight deviation from linearity was observed. In repeated administration, the linear disposition of rilmenidine with dose was confirmed. PMID- 2894159 TI - Pharmacokinetics of rilmenidine. AB - Rilmenidine, an alpha 2-adrenoceptor agonist, was studied (1 mg single dose) in order to determine the effects of pathology on its basic pharmacokinetic parameters. Because of the mainly renal elimination of rilmenidine, studies involved hypertensive, elderly hypertensive, renal insufficient and hepatic insufficient patients. Hypertension was found to influence neither the absorption, the distribution nor the elimination processes; the linearity in the range of 1 to 2 mg and the absence of accumulation in long-term treatment were confirmed. In contrast, in the elderly, the absorption phase was delayed. The slight decrease in the apparent volume of distribution (-12%), with a notable decrease in the apparent total clearance (-50%) led to a prolonged elimination half-life (+50%). In renal failure, linear relations between the degree of renal impairment and the elimination parameters were shown. These relations allow the evaluation of the predicted steady-state level of rilmenidine for a given degree of renal failure. In hepatic insufficiency, the modification of rilmenidine disposition concerned exclusively the elimination phase in which apparent clearance was decreased approximately 20%. In conclusion, these results lead to a decreased dosage regimen in patients with severe renal failure. PMID- 2894160 TI - Pharmacology of the alpha 2-adrenoceptor agonist rilmenidine. AB - Most alpha 2-adrenoceptor agonists developed so far will penetrate into the brain, thus causing central hypotensive activity, mediated by the stimulation of alpha 2 adrenoceptors in the region of the nucleus tractus solitarii, the vasomotor center and the nucleus of the vagus nerve. The central alpha 2 adrenoceptors are probably located at postjunctional (postsynaptic) sites. Their stimulation causes sympathoinhibition and thus a decrease in blood pressure and heart rate. The central hypotensive effect is the dominating activity of all alpha 2-adrenoceptor agonists developed so far, of which clonidine, guanfacine and alpha-methyl-DOPA (which is converted into alpha-methyl-noradrenaline) are the prototypes. Peripheral postsynaptic effects probably do not greatly contribute to the hypotensive activity of these drugs. Sedation, also mediated by central alpha 2 adrenoceptors is the major adverse reaction to these antihypertensive agents. More selective alpha 2-adrenoceptor agonists (B-HT 920, azepexole, UK 14,304) appear to display the same pattern of hypotensive and sedative activities as the nonselective compounds like clonidine. After the general survey on centrally acting alpha 2-adrenoceptor agonistic drugs, the pharmacologic profile of the new oxazoline derivative, rilmenidine, (S 3341) was compared with that of the classic compound, clonidine. In all current animal and in vitro models, rilmenidine was characterized as a clonidine-like, centrally acting antihypertensive drug. Thus, its central hypotensive activity proved mediated by the stimulation of central alpha 2 adrenoceptors. In radioligand binding studies, rilmenidine proved somewhat more selective for alpha 2 adrenoceptors, but this selectivity was not reflected by a clearly different pharmacologic profile of the drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894161 TI - Dose and concentration-effect relations for rilmenidine. AB - The dose-effect and concentration-effect relations of rilmenidine, a new alpha 2 agonist, were evaluated for the hemodynamic and side-effect responses to single oral doses. Two studies were performed in a double-blind manner: study I in 8 healthy subjects and study II in 10 hypertensive patients. In the course of five 24-hour periods, each separated by at least 1 week, the following 5 treatments were administered in a random order: placebo, rilmenidine (0.5, 1, 2 and 3 mg). Blood pressure was measured with a Roche arteriosonde (study I) or a sphygmomanometer (study II). Sedation was measured using a visual analog scale. Dry mouth was assessed by measuring the salivary flow (study I) or by visual analog scale (study II). Plasma concentration of rilmenidine was assayed by gas chromatography linked with mass spectrometry. The antihypertensive and sedative effects (area under curve) were directly related to the dose and to the log of the plasma concentration of rilmenidine. In contrast to the 2- and 3-mg doses, rilmenidine (0.5 and 1 mg) did not induce orthostatic hypotension, a significant decrease in heart rate or a significant dryness of mouth. At doses of 0.5 and 1 mg, the effects of rilmenidine on sedation were not consistent in both studies: sedation was significant in study I but did not differ from placebo in study II. These studies show that rilmenidine, in common with other alpha 2 agonists, decreases blood pressure in a dose-dependent manner, in normotensive as well as in hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894162 TI - Hemodynamic and electrophysiologic effects of a new alpha 2-adrenoceptor agonist, rilmenidine, for systemic hypertension. AB - The hemodynamic and electrophysiologic effects of rilmenidine were examined after single oral administration to hypertensive patients. In 8 untreated hypertensive patients, cardiac output, pulmonary pressure and blood pressure were measured before and for 10 hours after the administration of 25 micrograms/kg of rilmenidine (1.3 to 2.4 mg, mean 1.88). In addition, electrophysiologic investigations were performed before and 2 hours after administration. Hemodynamics were repeated in 8 other hypertensive patients receiving 50 micrograms/kg rilmenidine (3.0 to 4.8 mg, mean 3.85 mg). The electrophysiologic study was repeated in 8 other hypertensive patients receiving 50 micrograms/kg of rilmenidine (3.2 to 4.4 mg, mean 3.90). In contrast to the results obtained at the dose of 50 micrograms/kg, there was no significant variation in pulmonary arterial pressure, cardiac index or stroke index after administration of 25 micrograms/kg. No significant variation was observed in heart rate, sinus function, conduction parameters or atrial, nodal and ventricular refractory periods after administration of 25 and 50 micrograms/kg. Rilmenidine, after single oral administration at the 25 micrograms/kg dose, led to a significant reduction in blood pressure and peripheral resistance without any significant change in cardiac output; the 25- and 50-micrograms/kg doses led to no alteration in heart rate and cardiac electrophysiology. PMID- 2894163 TI - Noninvasive study of cardiac structure and function after rilmenidine for essential hypertension. AB - The hemodynamic effects of rilmenidine (S 3341) were evaluated noninvasively by aortic Doppler velocimetry, M-mode echocardiography and phonocardiography in hypertensive patients treated for 28 days. After a 2-week placebo run-in period, patients with mild hypertension (group I, n = 8, mean diastolic blood pressure [BP] = 97.18 +/- 0.65 mm Hg) received 1 mg of rilmenidine each morning and patients with moderate hypertension (group II, n = 6, mean diastolic BP = 107.62 +/- 1.18 mm Hg) received 1 mg twice daily. The hemodynamic variations in both groups after the first administration (day 1) showed that during the first 3 hours, mean arterial pressure and cardiac index (CI) were significantly reduced, whereas total peripheral resistance (TPR) was increased. From the third to the fifth hour, the decrease in mean arterial pressure was maintained, CI was higher than initial values and TPR decreased, indicating a persistent vasodilator effect. On day 28, hemodynamic variations were similar but of a lower amplitude. Before administration on day 28, a significant decrease in systolic and diastolic BP was observed, demonstrating that the antihypertensive activity of 1 mg was maintained for 24 hours, with a significant reduction in TPR and no modification of CI or stroke index. The M-mode and phonocardiographic left ventricular function indexes remained unchanged. Rilmenidine has a prolonged antihypertensive activity with a chronic vasodilator effect and no negative inotropic effect. PMID- 2894164 TI - Efficacy and acceptability of rilmenidine for mild to moderate systemic hypertension. AB - A double-blind multicenter trial compared rilmenidine with placebo in the treatment of 126 patients with mild to moderate hypertension after a 4-week placebo run-in period. Patients with mild hypertension (study 1) with mean supine diastolic blood pressure (BP) between 95 and 104 mm Hg received either rilmenidine 1 mg/day (n = 31) or placebo (n = 35) for 4 weeks. In study 2, patients with moderate hypertension (mean supine diastolic BP between 105 and 115 mm Hg) received either rilmenidine 1 mg twice a day (n = 30) or placebo twice a day (n = 30) for 4 weeks. All 61 patients taking rilmenidine completed the study; 8 of the 65 patients taking placebo were withdrawn because of an increase in BP. Rilmenidine significantly reduced mean systolic and diastolic BP compared with placebo in both studies. BP was normalized (systolic less than 160 mm Hg and diastolic less than or equal to 90 mm Hg in 61% of the patients taking rilmenidine as opposed to 23% of those taking placebo (p less than 0.001). There was no significant difference in the incidence of either dry mouth or daytime drowsiness between rilmenidine, 1 mg/day, and placebo. Dry mouth was significantly more frequent with rilmenidine, 2 mg/day, than with placebo, but this difference was transient and no longer significant at the end of the study. No unexpected adverse effects occurred. Rilmenidine as single therapy appears to be effective and well accepted in the management of mild to moderate hypertension, in particular at the 1-mg/day dose, which normalized 84% of mild hypertensive patients and did not induce any significant adverse effects compared with placebo. PMID- 2894165 TI - A multicenter double-blind comparative study of rilmenidine and clonidine in 333 hypertensive patients. AB - The efficacy and acceptability of rilmenidine were studied in a double-blind clonidine-controlled multicenter trial; after a 4-week placebo run-in period, patients with supine diastolic blood pressure (BP) between 95 and 115 mm Hg received as monotherapy either rilmenidine or clonidine over 6 weeks. The initial dose (rilmenidine 1 mg/day or clonidine 0.15 mg/day) was doubled (1 mg or 0.15 mg twice a day, respectively) after 2 weeks if diastolic BP remained greater than or equal to 90 mm Hg. Three hundred and thirty-three patients (mean age 57.8 +/- 0.7 years) with a systolic BP of 170.53 +/- 0.92 mm Hg and a diastolic BP of 101.57 +/- 0.30 mm Hg were randomly divided into 2 homogenous groups (rilmenidine, n = 162 and clonidine, n = 171). All patients taking rilmenidine completed the trial. Seventeen patients taking clonidine (10%, p less than 0.01 vs rilmenidine) were withdrawn because of severe side effects. Systolic and diastolic BP were significantly reduced in both groups at every examination (at 2, 4 and 6 weeks). The mean decreases in supine and erect BP were identical in both groups: systolic BP 19 mm Hg and diastolic BP 12 mm Hg after 6 weeks. BP was normalized (systolic BP less than 160 and diastolic BP less than or equal to 90 mm Hg) in 57% of patients taking rilmenidine and 56% of patients taking clonidine (60% of normalized patients had been taking the single dose in both groups).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894166 TI - Antihypertensive efficacy and acceptability of rilmenidine in elderly hypertensive patients. AB - Elderly hypertensive patients (older than 70 years, with a diastolic blood pressure [BP] between 95 and 114 mm Hg) were entered into a study after a 2-week wash-out period and randomized to 2 parallel groups: rilmenidine (n = 28) and methyldopa (n = 30). The initial dose (rilmenidine, 1 mg once daily A.M. or methyldopa, 250 mg twice daily) was doubled (1 mg twice daily or 500 mg twice daily, respectively) on day 21 if supine diastolic BP remained greater than 90 mm Hg. After a 6-week treatment period (days 0 to 42, with weekly examinations), the effects of treatment withdrawal (day 42) were evaluated twice daily (days 43 to 45), with a final examination on day 49. Most of the 58 patients (70%) (aged 81.5 +/- 0.8 years) with a mean diastolic BP of 100.2 +/- 0.7 mm Hg remained treated with the initial dose in both groups. Efficacy in both groups was identical on day 42: decrease in systolic and diastolic BP of approximately 18 mm Hg, with 85% of patients having BP levels normalized (supine diastolic BP less than or equal to 90 mm Hg). Compared with the reference period, no increase in adverse effects was noted apart from a moderate dryness of mouth in 15% of patients in both groups; no orthostatic hypotension was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894167 TI - Treatment of systemic hypertension in insulin-treated diabetes mellitus with rilmenidine. AB - The effects of a new alpha 2 agonist (S 3341 or rilmenidine) on blood pressure (BP), glycemic control, lipid metabolism and renal function were investigated during a 16-week open study in 29 insulin-treated diabetic patients with mild to moderate hypertension. There were 17 men and 12 women aged 50.9 +/- 2.2 years (mean +/- standard error of the mean). Duration of diabetes and insulin therapy was 218 +/- 24 and 143 +/- 30 months. After 2 weeks of placebo, systolic and diastolic BP was 165 +/- 3 and 97 +/- 0.5 mm Hg, respectively (supine). Rilmenidine (S 3341) given alone at daily doses of 1 or 2 mg according to the clinical response led to a prompt and sustained decrease of systolic and diastolic BP (159 +/- 4 and 88 +/- 1 mm Hg after 2 weeks; 149 +/- 3 and 85 +/- 1 mm Hg after 12 weeks; p less than 0.01). Seventeen patients (59%) had normal BP (systolic BP less than 160; diastolic BP less than 90 mm Hg, supine) after 12 weeks of S 3341. Diuretics were associated with S 3341 for the nonresponders at week 12; this led to normalization of BP in 90% of the patients at the end of the study. Glycemic control was assessed by home glucose monitoring (5 determinations/1 day per week), 24-hour glucosuria and postprandial plasma glucose at the outpatient clinic (n = 7) as well as by the measurement of the glycosylated hemoglobin. None of these parameters was significantly affected by S 3341.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894168 TI - Efficacy and safety of rilmenidine for arterial hypertension. AB - To assess the long-term acceptability and efficacy of rilmenidine (S 3341), patients with placebo-resistant hypertension (diastolic blood pressure [BP] greater than or equal to 95 mm Hg and less than 115 mm Hg) were included in an open 1-year treatment study. Eight examinations allowed treatment adaptation if diastolic BP remained greater than or equal to 90 mm Hg (monotherapy with rilmenidine, 1 or 2 mg/day, followed by the addition of a diuretic, then tritherapy). Three hundred seventeen patients, aged 58.0 +/- 0.7 years, were included. Two hundred sixty-nine were followed for 1 year and 48 withdrew from the trial without any symptom suggesting a withdrawal syndrome: 4 because of adverse effects; 6, lack of efficacy despite triple therapy; 9, intercurrent diseases; 10, noncompliance independent of adverse effects; 18, personal reasons not associated with treatment; and 1, lost to follow-up. On the 12th month, the decrease in supine systolic and diastolic BP reached 25 and 17 mm Hg with monotherapy (n = 150), 26 and 17 mm Hg with double therapy (n = 90) and 20 and 15 mm Hg with triple therapy (n = 29). BP was normalized (diastolic BP less than or equal to 90 mm Hg) on months 6 and 12 in 80 and 84% of the patients, respectively. Monotherapy was maintained in 66 and 60% of these patients, respectively, two-thirds being treated with 1 mg once daily. Adverse effects with monotherapy were mainly observed at the beginning of treatment in 3 to 8%: dry mouth, asthenia, gastralgia, palpitations, drowsiness, insomnia; other adverse effects were rare (1 to 2%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894170 TI - Clinical trials in ulcerative colitis: II. Historical review. PMID- 2894169 TI - Effects of encainide, flecainide, imipramine and moricizine on ventricular arrhythmias during the year after acute myocardial infarction: the CAPS. AB - The National Heart, Lung, and Blood Institute initiated the Cardiac Arrhythmia Pilot Study (CAPS) to evaluate the feasibility of suppressing ventricular arrhythmias after acute myocardial infarction. Ten centers enrolled 502 patients younger than 75 years of age with greater than or equal to 10 ventricular premature complexes (VPC) per hour in a 24-hour electrocardiographic recording and a left ventricular ejection fraction greater than 20%. Patients were enrolled 6 to 60 days after acute myocardial infarction and randomized to 1 of 5 treatment tracks with 2 drugs that included encainide, flecainide, imipramine, moricizine or placebo. During a double-blind drug and dose selection phase, investigators were permitted to change drug or dosage to achieve greater than or equal to 70% suppression in VPC frequency and greater than 90% suppression of runs of VPC with the exception of patients assigned to placebo, who continued receiving it. Patients were followed for a year after randomization. Patients in the 5 treatment arms were similar in age, sex, clinical characteristics, VPC frequency, left ventricular ejection fraction and concomitant drug treatment. As first drugs, encainide and flecainide had higher efficacy rates, 79% and 83%, respectively, than imipramine, 52%, moricizine, 66%, or placebo, 37%. Encainide and flecainide also had high efficacy rates, 68% and 69%, in patients who failed imipramine or moricizine. Encainide, flecainide and moricizine were well tolerated. These 3 drugs had intolerable adverse effect rates of 6% or less, i.e., similar to placebo. More than 70T of the patients who started the follow-up phase on encainide, flecainide or moricizine remained on these drugs to the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894171 TI - Upper respiratory tract involvement in adult T-cell leukemia. AB - Adult T-cell leukemia (ATL) is characterized by peripheral lymph node enlargement, hepatosplenomegaly and skin lesions. The association of local mass lesions of other organs with ATL is extremely rare. This report describes a 57 year-old woman with chronic type ATL with associated local tumor masses in the nasal cavity, paranasal sinuses and larynx as well as skin infiltration. Histologic investigation of the skin lesion and nasal mucosa revealed non-Hodgkin lymphoma, diffuse, mixed type. Her chief complaints were progressive dyspnea and hoarseness. Leukemic cell masses in her upper respiratory tract caused narrowing of the airway, which was responsible for her complaints. PMID- 2894172 TI - Localization of the gene for X-linked nephrogenic diabetes insipidus to Xq28. AB - X-linked nephrogenic diabetes insipidus (NDI) was segregating in a large Indiana family. It was tested for linkage of the NDI gene to X-chromosome molecular markers. Maximum lod scores of 3.15 and 3.01 (theta = 0) obtained for the molecular markers F8A (F8C) and DXS15 (DX13) respectively, indicate that the NDI gene is located in Xq28. A lod score of 3.61 (theta = 0) was obtained with multipoint linkage analysis of F8A and DXS15. PMID- 2894173 TI - Stimulating intestinal afferents reflexly activates cardiovascular system in cats. AB - Capsaicin and bradykinin stimulate afferents from certain viscera to reflexly activate the cardiovascular system; however, whether these agents evoke similar reflex responses when applied topically to the intestine is not known. Therefore, in cats anesthetized with methoxyflurane, we applied capsaicin (10 micrograms) or bradykinin (0.5 microgram) to the serosal surface of the jejunum. Additionally, we topically applied bethanechol chloride, a synthetic choline ester with little direct cardiovascular effects, to evoke marked contraction of the smooth muscle of the jejunum. Capsaicin evoked significant (P less than 0.05) increases in mean arterial pressure (105 +/- 4 to 119 +/- 4 mmHg, mean +/- SE), first derivative left ventricular pressure (dP/dt) at 40 mmHg (2,698 +/- 134 to 3,105 +/- 155 mmHg/s), systemic vascular resistance (0.63 +/- 0.15 to 0.68 +/- 0.15 peripheral resistance units), and heart rate (196 +/- 14 to 205 +/- 15 beats/min), whereas aortic flow did not change. In a dose-dependent fashion, bradykinin and bethanechol each caused cardiovascular activation as well as a marked contraction of the smooth muscle in the segment of jejunum to which they were applied. In contrast, capsaicin produced no detectable contraction of visceral smooth muscle. Removal of the celiac and superior mesenteric ganglia abolished the cardiovascular responses evoked by capsaicin and bradykinin. Thus, in cats, stimulating intestinal afferents by topically applying capsaicin or bradykinin reflexly activates the cardiovascular system. Furthermore, although mechanoreceptors may contribute to the responses evoked by bradykinin and bethanechol, the capsaicin-related responses likely are mediated exclusively by chemically sensitive receptors. PMID- 2894174 TI - Toward rational pharmacotherapy for posttraumatic stress disorder: an interim report. AB - There is growing evidence that medication can alleviate symptoms associated with posttraumatic stress disorder (PTSD). Recent research also suggests that PTSD has a unique biological profile consisting of alterations in sympathetic arousal, the neuroendocrine system, and the sleep/dream cycle. This profile distinguishes PTSD from both major depression and panic disorder. Medication appears to alleviate PTSD symptoms associated with sympathetic hyperarousal and intrusive recollections of the trauma but seems ineffective against avoidant symptoms. Pharmacotherapy alone is rarely sufficient to provide complete remission of PTSD. Symptom relief provided by medication facilitates the patient's participation in individual, behavioral, or group psychotherapy. PMID- 2894176 TI - Insulin resistance after oral glucose tolerance testing in patients with major depression. AB - An association between affective disorders and alterations in glucose utilization has been recognized. The authors administered a 5-hour oral glucose tolerance test (GTT) to 28 depressed patients and 21 healthy volunteer control subjects and measured serum glucose as well as plasma insulin and glucagon responses. Depressed patients demonstrated significantly higher basal glucose levels, greater cumulative glucose responses after the GTT, and larger cumulative insulin responses after the GTT than control subjects. Values for cumulative glucagon did not significantly differ between groups. These findings indicate the presence of a functional state of insulin resistance during major depressive illness and suggest the presence of a more generalized biological disturbance in some depressed patients. PMID- 2894177 TI - Use of arylsulfatase A in chronic psychiatric patients. PMID- 2894175 TI - Clorazepate and lorazepam: clinical improvement and rebound anxiety. AB - Sixty-two anxious patients were treated under double-blind conditions for 4 weeks with either clorazepate or lorazepam. Two-thirds of each treatment group were then switched abruptly to placebo for 2 weeks, while one-third continued to receive active medication. Two major findings were obtained. About 70% of the patients maintained improvement during the 2-week placebo period. Some patients, however, experienced rebound anxiety, which appeared to be more intense and occurred earlier when placebo was substituted for a benzodiazepine with a short half-life (lorazepam) than for one with a long half-life (clorazepate). The clinical relevance of these findings is discussed. PMID- 2894178 TI - Ethical issues in drug studies. PMID- 2894179 TI - Mechanism of neuroleptic-associated priapism. PMID- 2894180 TI - Total intravenous anaesthesia for military surgery. A technique using ketamine, midazolam and vecuronium. AB - Ketamine and midazolam were used for induction of anaesthesia and by continuous intravenous infusion for maintenance to assess their suitability for use in a total intravenous anaesthetic technique in the management of battle casualties. Muscular relaxation was provided by vecuronium and the patients' lungs ventilated with air. Ketamine was infused at a rate of 2 mg/kg/hour. This was achieved by mixing ketamine 200 mg, midazolam 5 mg and vecuronium 12 mg in 50 ml normal saline. The rate of infusion of the mixture (ml/hour) was then equal to 50% of the body weight in kg. The technique proved to be simple, effective and versatile and should be adaptable for use in the management of battle casualties. PMID- 2894181 TI - Temazepam and recovery in day surgery. AB - A double-blind trial of temazepam premedication for day cases was undertaken. Effective anxiolysis was recorded in the groups that received temazepam 10 or 20 mg and there was no prolongation of delayed recovery times as measured by memory test cards. All patients were discharged from the day unit 3 hours after the administration of general anaesthesia. PMID- 2894182 TI - Anaphylactoid reaction to oral premedication with temazepam and promethazine. PMID- 2894183 TI - [Effects and side effects of somatostatin]. AB - Somatostatin, a peptide hormone with a wide range of actions, was first described in 1973. It is found in neurons of the central and peripheral nervous systems and D cells of the gut and pancreas. Somatostatin acts as a neurotransmitter, a local tissue factor, and a hormone. The intrinsic metabolic effects of somatostatin have been well investigated during the past 10 years. It inhibits the release of gastrointestinal secretions and delays the absorption of glucose and amino acids. Somatostatin inhibits the effects of the release of several of the hormones involved in water-electrolyte homeostasis. It exerts an influence on the regulation of several endocrine and exocrine functions, acting as a "shock absorber". In the nervous system somatostatin functions as a neurotransmitter; intrathecal application causes characteristic changes in the motor system and behavioral aberrations. Furthermore, it has been suggested that it may be a potent analgesic. Side-effects seen during animal experiments are many: marked increases in blood glucose, various behavioral changes, respiratory failure, and death. This article compares the effects and potential side-effects of somatostatin with particular regard to the recent observation that this substance may be a potent analgesic. PMID- 2894185 TI - Epidural opiates and urinary retention: new models provide new insights. PMID- 2894184 TI - Interactions of vecuronium and atracurium in an in vitro nerve-muscle preparation. AB - Atracurium and vecuronium were compared when given alone and in combination in the in vitro rat phrenic nerve-hemidiaphragm preparation stimulated via the phrenic nerve. The slopes of the log dose response curves of atracurium and vecuronium were parallel; their ED50s were 1.12 +/- 0.0035.10(-5)M and 5.89 +/- 0.16.10(-6)M, respectively. The combination's log dose response curves were significantly shifted to the left when compared with those of either relaxant alone; an increased potency is displayed by the combination. These observations indicate nondepolarizing muscle relaxant synergy for the combination of equal proportions of vecuronium and atracurium. The synergistic interaction of vecuronium and atracurium in this in vitro-model is not dependent on pharmacokinetic factors such as uptake, distribution, and biodegradation as are present in the in vivo animal models and in humans. Synergy of vecuronium and atracurium in vitro is a new finding and is consistent with hypotheses of multiple receptor sites and different modes of action of the "competitive" neuromuscular blocking agents. This degree of synergy, seen in the in vitro animal data, if extrapolatable to humans, is probably of little clinical significance. PMID- 2894186 TI - The influence of respiratory-induced acid-base changes on the action of non depolarizing muscle relaxants in rats. AB - The influence of respiratory-induced acid-base changes on the action of non depolarizing muscle relaxants was investigated using the rat phrenic nerve hemidiaphragm preparation. Changes in pH were induced by changes in the CO2 concentration aerating Krebs' solution. In the absence of muscle relaxants, an increase in CO2 from 5% to 7.5% decreased (P less than 0.01) indirectly elicited twitch tension by 5.4 +/- 0.7% (mean +/- SEM), while a decrease in CO2 from 5% to 2.5% increased (P less than 0.01) twitch tension by 2.3 +/- 0.7%. With a change in CO2 from 2.5% to 7.5%, partial neuromuscular blockade produced by d-Tc or vecuronium was augmented (P less than 0.01), while that produced by metocurine, pancuronium, or alcuronium was reduced (P less than 0.01). With the change in CO2 from 7.5% to 2.5%, the neuromuscular blockade produced by d-Tc or vecuronium was reduced (P less than 0.01), while that produced by metocurine, pancuronium, or alcuronium was augmented (P less than 0.01). Dose-response study showed that 2.5% CO2 shifted the dose-response curves for d-Tc and vecuronium to the right (P less than 0.01) from those with 5% CO2, whereas 7.5% CO2 shifted them to the left (P less than 0.05). In contrast, neither 2.5% CO2 or 7.5% CO2 significantly shifted the dose-response curves for metocurine or pancuronium from those with 5% CO2. Their dose-response curves with 2.5% CO2 were to the left, instead of to the right, of those with 7.5% CO2 (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894187 TI - Esmolol and left ventricular function in the awake dog. AB - Hypotension has been the most frequently reported adverse reaction associated with infusion of the beta 1-adrenergic receptor antagonist esmolol. In some patients, this hypotension has apparently occurred independent of reduction in heart rate or systemic vascular resistance, suggesting decreased stroke volume. In the present study, the preload recuitable stroke work area (PRSWA) model was used to evaluate the negative inotropic effects of esmolol in nine chronically instrumented awake dogs. Left ventricular (LV) transmural pressure and minor axis diameter were measured by micromanometers and sonomicrometry, respectively. Vena caval occlusions were performed so that an analog of stroke work (area within LV transmural pressure-diameter loop) could be measured over a range of preloading conditions during esmolol infusions of 0, 100, 300, 1000, and 3000 micrograms/kg 1.min-1 (n = 9), and at 15 and 30 min after termination of esmolol (n = 8). The linear relationship between stroke work and end-diastolic diameter was characterized for each caval occlusion by a slope and x-intercept. PRSWA was calculated for each caval occlusion as slope/two times the square of the difference between x-intercept and the largest end diastolic diameter observed in the study of a particular dog. Heart rate was different from control (91 +/- 4) only at the highest esmolol dose (127 +/- 4). LV peak positive dP/dt, minor axis ejection shortening, stroke work, and PRSWA were depressed from control at esmolol doses greater than or equal to 300 micrograms.kg-1.min-1. All parameters except dP/dt recovered within 30 min following termination of esmolol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894188 TI - Muscle relaxation with succinylcholine or vecuronium does not alter the rate of CSF production or resistance to reabsorption of CSF in dogs. AB - The open ventriculocisternal perfusion method was used to determine the rate of cerebrospinal fluid (CSF) formation (Vf) and resistance to reabsorption of CSF (Ra) in halothane-anesthetized dogs with and without succinylcholine (n = 6) and with and without vecuronium (n = 6). Both Vf and Ra during the use of either muscle relaxant were not different than Vf and Ra when no muscle relaxant was used. Succinylcholine caused muscle fasciculations and raised CSF pressure transiently (increase of 5.5 +/- 1.0 cm H2O [mean +/- SD]), while vecuronium did not. When muscle relaxants were not used, it became difficult to distinguish the effects of cardiovascular and respiratory activity on the CSF pressure waveform, and the coefficient of variability for determination of cisternal outflow rates was increased, making Ra values less reliable. It is concluded that continuous infusion of succinylcholine or vecuronium do not affect Vf or Ra. When Vf and Ra are determined by the method of ventriculocisternal perfusion, immobilization of respiratory muscles improves both the reliability of Ra values and the usefulness of the CSF pressure waveform. If a muscle relaxant is used, either succinylcholine or vecuronium would be suitable for such studies. PMID- 2894189 TI - Epidural sufentanil for postoperative analgesia after cesarean section. PMID- 2894190 TI - Atracurium and vecuronium do not affect extraocular muscle function after outpatient surgery. PMID- 2894191 TI - Human retroviruses: HTLV-I, II, and III and their association with leukemia and AIDS. PMID- 2894192 TI - The origins of HIV-1 and HTLV-4/HIV-2. PMID- 2894193 TI - Human T-lymphotropic retrovirus infection in Italy. PMID- 2894196 TI - Familial occurrence of HTLV-I--associated myelopathy. PMID- 2894195 TI - The murine homeo domain protein Hox 1.1. PMID- 2894194 TI - Retroviral vector-mediated gene transfer and expression in nonhuman primates following autologous bone marrow transplantation. PMID- 2894197 TI - Neuronal unit activity patterns in behaving animals: brainstem and limbic system. PMID- 2894198 TI - Ethoexperimental approaches to the biology of emotion. PMID- 2894199 TI - Transformation of Clostridium perfringens L forms with shuttle plasmid DNA. AB - L-form (L-phase) cultures of Clostridium perfringens were tested for their transformability with plasmid DNA. Three L-form strains were transformable, but one, strain L-13, was superior to the others. This strain was easily and reproducibly transformed with previously described shuttle vectors which were derived from either C. perfringens or Escherichia coli. Strain L-13 was transformable by a variety of methods, and a new micromethod worked well under both aerobic and anaerobic conditions. The maximal number of transformants was attained after strain L-13 was exposed for 4 h to the transforming DNA and polyethylene glycol. Viable counts determined in tubes of semisolid brain heart infusion medium containing 10% sucrose, with or without 2 micrograms of tetracycline per ml, showed a transformation rate of 3.9 X 10(-5) (transformants per viable cells). PMID- 2894200 TI - Development of a new shuttle plasmid system for Escherichia coli and Clostridium perfringens. AB - We constructed a 7.9-kilobase-pair recombinant shuttle plasmid, designated pHR106, by combining desired segments of three plasmids: an Escherichia coli plasmid (pSL100) which provides a multiple cloning site, a Clostridium perfringens plasmid (pJU122) which provides a clostridial origin of replication, and an E. coli plasmid (pJIR62) which provides an E. coli origin of replication, an ampicillin resistance gene, and a chloramphenicol resistance gene of clostridial origin. The shuttle plasmid transformed E. coli HB101 with a frequency of 1 transformant per 10(4) viable cells and C. perfringens L-phase strain L-13 with a frequency of approximately 1 transformant per 10(6) viable cells. Because of the set of unique cloning sites and the chloramphenicol resistance marker, this shuttle plasmid should be particularly useful for studies of gene regulation and for enzyme production with C. perfringens. PMID- 2894201 TI - Structural relatedness between mosquitocidal endotoxins of Bacillus thuringiensis subsp. israelensis. AB - A mosquitocidal toxin gene, cloned from Bacillus thuringiensis subsp. israelensis, was introduced into mutant crystal-negative B. thuringiensis subsp. israelensis cells. Partial toxicity to mosquitos was restored. The 58-kilodalton cloned gene product is a minor protein component of B. thuringiensis subsp. israelensis crystals and is structurally related to a major, 135-kilodalton crystal toxin. PMID- 2894202 TI - Influence of amino acids on nitrogen fixation ability and growth of Azospirillum spp. AB - The utilization of amino acids for growth and their effects on nitrogen fixation differ greatly among the several strains of each species of Azospirillum spp. that were examined. A. brasiliense grew poorly or not at all on glutamate, aspartate, serine, or histidine as the sole nitrogen and carbon sources. Nitrogen fixation by most A. brasiliense strains was inhibited only slightly even by 10 mM concentrations of these amino acids. In contrast, A. lipoferum and A. amazonense grew very well on glutamate, aspartate, serine, or histidine as the sole nitrogen and carbon sources; nitrogen fixation, which was measured in the presence of malate or sucrose, was severely inhibited by these amino acids. It was concluded that growth on histidine as the sole source of nitrogen, carbon, and energy may be used for the taxonomic characterization of Azospirillum spp. and for the selective isolation of A. lipoferum. The different utilization of various amino acids by Azospirillum spp. may be important for their establishment in the rhizosphere and for their associative nitrogen fixation with plants. The physiological basis for the different utilization of glutamate by Azospirillum spp. was investigated further. A. brasiliense and A. lipoferum exhibited a high affinity for glutamate uptake (Km values for uptake were 8 and 40 microM, respectively); the Vmax was 6 times higher in A. lipoferum than in A. brasiliense. At high substrate concentrations (10 mM), the nonsaturable component of glutamate uptake was most active in A. lipoferum and A. amazonense.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894203 TI - Cutaneous-type adult T-cell leukemia/lymphoma. A unique clinical feature with monoclonal T-cell proliferation detected by Southern blot analysis. AB - A 60-year-old woman suffered from multiple subcutaneous nodules with a self limited clinical course. High titer of the antibody against the adult T-cell leukemia/lymphoma (ATL)-associated cell antigen was detected and atypical lymphocytes were present in less than 1% of the peripheral leukocytes. Tumor cells were identified by the molecular biology technique Southern blot analysis, which showed monoclonal cell expansion of the helper/inducer T cells integrated with human T-cell lymphotropic virus type I/adult T-cell leukemia virus. This patient was diagnosed as having the cutaneous type of smoldering ATL in a very early stage. In this case, only gene analysis of the skin lesion could facilitate making an early differential diagnosis of ATL from other lymphoproliferative diseases, including nonviral cutaneous T-cell lymphoma and benign lymphoid hyperplasia. PMID- 2894204 TI - Circulating inhibitor bound elastase in patients with ankylosing spondylitis and rheumatoid arthritis and the influence of sulphasalazine treatment. AB - The plasma concentration of granulocyte elastase in complex with alpha 1 proteinase inhibitor was determined in 42 patients with ankylosing spondylitis (AS) and 33 patients with rheumatoid arthritis (RA). Significantly raised levels of plasma elastase were found in patients with RA, whereas patients with AS had normal values. No correlation was seen between the elastase values and erythrocyte sedimentation rate (ESR), serum haptoglobin, immunoglobulins, or polymorphonuclear cell (PMN) count in either of the patient groups. A correlation was found between the Ritchie index and plasma elastase in patients with RA. After three months' treatment with sulphasalazine a clinical improvement was seen and this paralleled a reduction of the acute phase reaction in both patient groups. A reduction of the circulating elastase values was seen in the patients with RA, whereas no change was seen in patients with AS. PMID- 2894206 TI - Genetic monitoring of inbred mouse strains maintained at the Bhabha Atomic Research Centre, Bombay: serological typing for H-2 haplotypes and lymphocyte differentiation markers. AB - Seven inbred mouse strains, AKR, CBA, C3H, C57BL/6, C57BR/cd, DBA/2 and Swiss, maintained at the Bhabha Atomic Research Centre, Bombay (designated Bh) were monitored for compatibility with standard strains as well as for genetical homogeneity. For this purpose, five individual mice from each strain were typed serologically for H-2 class I and class II antigens and for lymphocyte differentiation markers, Thy-2, Lyt-1, Lyt-2, TL and Ly-10. In this latter testing, 15 inbred strains from the Institute of Immunology and Experimental Therapy, Wroclaw (designated Iiw) were included. Results revealed that none of the tested strains deviated from the reactivity pattern of standard strains described in the literature. No evidence of genetic contamination was found in any strain. In the course of these studies, several interesting observations were made: (1) Swiss/Bh strain is an intra H-2 recombinant, probably KdAbEbDbTlab, (2) C3H/Bh and C3H/Iiw are Ly-10a and Ly-10b, respectively (3) some (CBA, C3H, DBA/2 and GR/S) but not C58/Ly-2a strains cross reacted with high concentration of anti Lyt-2.2 monoclonal antibody HO.2.2. PMID- 2894207 TI - Malignant peripheral nerve sheath tumor and pheochromocytoma. A composite tumor of the adrenal. AB - An adrenal composite tumor of pheochromocytoma and malignant peripheral nerve sheath tumor (PNST) is described in a 39-year-old woman in whom PNST component appeared to have undergone further malignant degeneration, resulting in a highly anaplastic sarcoma with rapidly progressive clinical course. PMID- 2894205 TI - Metabolic intervention in surgical patients. An assessment of the effect of somatostatin, ranitidine, naloxone, diclophenac, dipyridamole, or salbutamol infusion on energy and protein kinetics in surgical patients using stable and radioisotopes. AB - We have assessed the effect of a variety of forms of metabolic intervention on both energy and protein metabolism in 44 severely ill surgical patients. The patients were studied either in the basal state or while receiving total parenteral nutrition (TPN), and the metabolic effects were assessed using the primed-constant infusion of a combination of stable isotopes and radioisotopes. Somatostatin infusion, either in the basal state or in the TPN, did not change glucose kinetics, but there was a significant decrease in the rate of net protein catabolism (NPC). In the basal studies the rate of NPC decreased from 3.4 +/- 0.7 g/kg/d to 2.9 +/- 0.7 g/kg/d (p less than 0.002), while in the TPN patients the corresponding values were 1.48 +/- 0.61 g/kg/d and 1.10 +/- 0.50 g/kg/d, respectively (p less than 0.005). Histamine type 2 blockade with ranitidine did not significantly alter glucose kinetics, but in both the TPN patients and in the basal state ranitidine was associated with a significant decrease in the rate of NPC. In the basal state rate of NPC was 2.44 +/- 0.53 g/kg/d and during ranitidine infusion the value was 2.08 +/- 0.42 g/kg/d (p less than 0.04). Naloxone infusion did not alter glucose kinetics, but there was a significant decrease in the rate of NPC from a basal value of 2.6 +/- 0.6 g/kg/d to 2.3 +/- 0.5 g/kg/d (p less than 0.04). The infusion of the prostaglandin antagonists diclofenac or dipyridamole resulted in increases in the plasma insulin level, and as a result glucose turnover decreased in both groups. In the diclofenac group the rate of glucose turnover decreased from 14.4 +/- 1.7 mumol/kg/min to 12.6 +/- 1.3 mumol/kg/min (p less than 0.02). Neither prostaglandin antagonist resulted in any significant change in the rate of NPC. Beta-adrenergic stimulation with salbutamol resulted in a significant increase in glucose turnover from 12.1 +/- 1.1 mumol/kg/min to 13.4 +/- 0.9 mumol/kg/min (p less than 0.02), and the rates of appearance (Ra) of both alanine and free fatty acids (FFAs) also increased. Alanine Ra increased from 11.7 +/- 2.5 mumol/kg/min to 12.8 +/- 3.0 mumol/kg/min, and the corresponding values for FFA turnover were 7.6 +/- 1.1 mumol/kg/min and 10.3 +/- 2.1 mumol/kg/min (p less than 0.03), respectively. Salbutamol infusion did not result in any significant change in the rate of NPC.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2894209 TI - Inhibition by H1-antihistamines of the uptake of noradrenaline and 5-HT into rat brain synaptosomes. PMID- 2894208 TI - The toxicity of phomopsin for sheep. AB - Pure phomopsin was administered to young Merino x Border Leicester wethers by single subcutaneous (SC) and by single and multiple intraruminal (IR) injection. The toxicity after IR injection was influenced by the size of individual doses and the time over which the total dose was given. At high levels of ingestion the toxicity of phomopsin may be limited by absorption rates; with low daily doses the capacity to repair liver damage may be sufficient to prevent cumulative effects. By SC injection a single dose of 10 micrograms/kg approximated the LD50. By IR injection the overall clinical, biochemical and histological responses closest to these of this SC dose resulted from a single dose of 1,000 micrograms/kg. The same total dose administered at daily rates of 50 or 200 micrograms/kg was more toxic and killed all sheep. A single dose of 500 micrograms/kg caused significant liver damage, but no deaths. Single doses of 125 and 250 micrograms/kg and repeated daily doses of 12.5 micrograms/kg over 16 weeks caused no detectable tissue damage. Inappetence was the most sensitive indicator of phomopsin toxicity. About 10% of the sheep differed substantially from the rest of the flock in their susceptibility to phomopsin poisoning. PMID- 2894211 TI - Genotypic and phenotypic markers in the differentiation of Neisseria gonorrhoeae strains. AB - Restriction enzyme (RE) patterns, using Hind III enzyme, were analysed on 101 urogenital strains of Neisseria gonorrhoeae. The strains were also analysed serologically, using monoclonal antibodies, and tested for nutritional requirements by auxotyping. In addition, testing susceptibility to doxycycline was performed by an agar-dilution method. The strains were distributed into 23 RE patterns, of which the five most common accounted for 67.3% of all isolates. The same strains were distributed into 17 serovars, of which the four most common accounted for 77.3% of all isolates. Eleven auxotypes were demonstrated, of which the four most common accounted for 85.1% of all isolates. When the methods were combined, 38 combinations of RE patterns and serovars, 25 combinations of RE patterns and auxotypes, and 31 combinations of serovars and auxotypes were seen. Combining all three methods, 40 combinations of RE patterns, serovars and auxotypes were found. Correlations were particularly seen between RE patterns and auxotypes. The strains were moderately sensitive to doxycycline, those with serological markers for WII/WIII being less sensitive than those with markers for WI. PMID- 2894210 TI - [Synthesis of the highly cardioselective beta-sympatholytic pacrinolol]. AB - The synthesis is described of the enantiomerically pure (-)-3-(3,4 dimethoxyphenylethylamino)-2-hydroxypropoxy] phenyl]-cis-crotonic acid nitrile (13b) (free base) and its hydrochloride (13c) (pacrinolol, Hoe 224 A) starting from p-hydroxyacetophenone (1) and racemic epichlorohydrin (2). The p-(2,3 oxidopropoxy)acetophenone (2) resulting from this reaction is C-homologisized to (8); reactions of this with homoveratrylamine (9) leads to (10a), the racemic structural analog of (13b). Resolution of the racemate is achieved by fractional crystallisation of the diastereoisomeric mandelates (13a) and (14a) to afford the enantiomerically pure title compound (13c) and its dextrarotatory optical antipode (14c). Structural confirmation of (13b) and (13c) was achieved through physicochemical and spectroscopic data especially from the 1H-NMR- and MS spectra. Pacrinolol (13c) is a highly cardioselective beta-sympathicolytic with significant and long acting blood pressure lowering properties (intravenous and oral in the dog). PMID- 2894212 TI - Upper limb blood flow during hexamethonium-induced hypotension. Studies in patients anaesthetized with halothane. AB - We report the effect of hypotensive anaesthesia on blood flow in the upper limbs of 17 patients before the start of surgery. Under light halothane-oxygen anaesthesia, patients (n = 17) were given hexamethonium 0.5-1.0 mg kg-1. Forearm blood flow (FBF), hand blood flow (HBF) and systemic arterial pressure (AP) were measured before, and 9 and 18 min after the administration of hexamethonium. During the control period of halothane anaesthesia, HBF was AP-dependent, but FBF was not. Hexamethonium produced a statistically significant (P less than 0.001) decrease in systolic AP by 9 and 18 min, but significant reductions in FBF and HBF were seen only at 9 min. During the hypotensive period neither HBF nor FBF correlated with the systolic AP, which had decreased from an average of 98 mm Hg to an average of 65 mm Hg (range 95-50 mm Hg), but the changes in HBF and FBF did correlate with the changes in systolic AP. As a secondary factor, the control FBF correlated inversely with the reduction in FBF after hexamethonium. We concluded that hypotension induced by hexamethonium during halothane anaesthesia produced a transient reduction in limb blood flow that was dependent on the change in AP. A range of systolic AP from 95 to 50 mm Hg did not correlate with either FBF or HBF during the hypotensive period. PMID- 2894213 TI - Muscle relaxation in patients with Duchenne's muscular dystrophy. Use of vecuronium in two patients. AB - Cumulative 50% and 90% neuromuscular blocking doses of vecuronium were determined in two 4-yr-old boys with Duchenne's muscular dystrophy. Vecuronium 20 micrograms kg-1 was required for 50% twitch depression in both patients. The 90% blocking doses were 43 and 57 micrograms kg-1. Although these data do not indicate a greater than normal sensitivity to vecuronium, the recovery time (75-25% block) of twitch tension was three to almost six times as long as in normal children. The evoked compound EMG, additionally recorded in one patient, reflected almost the same dose-response relationship as twitch tension, yet the EMG recovered faster than the twitch. The present findings do not exclude an increased sensitivity to neuromuscular blocking drugs in a larger population of patients with muscular dystrophy. Thus, the titration of the individual neuromuscular blocking dose with the aid of a nerve stimulator is mandatory. During a previous anaesthetic, cardiac arrest and acute rhabdomyolysis had occurred in one patient. The substitution of suxamethonium by vecuronium, or probably any other non depolarizing myoneural blocking drug of intermediate or short duration of action, may help to avoid this complication. PMID- 2894214 TI - Plasma prolactin concentrations during high-dose opioid anaesthesia. PMID- 2894215 TI - Ketanserin in essential hypertension: use as monotherapy and in combination with a diuretic or beta-adrenoceptor antagonist. AB - 1. The antihypertensive efficacy and tolerability of twice-daily treatment with the 5-hydroxytryptamine antagonist ketanserin were examined in a double-blind, placebo-controlled trial of 7 weeks duration in 56 hypertensive patients. Twenty were untreated, 20 were already taking bendrofluazide 5 mg daily, and 16 were already taking atenolol 100 mg daily. Randomisation was stratified to compare ketanserin with placebo as monotherapy (n = 20), when added to bendrofluazide (n = 20), and when added to atenolol (n = 16). 2. The antihypertensive effect of ketanserin in all patients completing the study (mean daily dose 71 mg) was 10/6 mm Hg supine (P less than 0.01/P less than 0.01) and 6/6 mm Hg standing (NS/P less than 0.01) when blood pressure was measured 2 h after the morning dose. Responses were similar in patients taking ketanserin as monotherapy, in addition to bendrofluazide, and in addition to atenolol, with reductions in mean arterial pressure of 4.6, 7.4 and 8.9 mm Hg respectively. 3. Ketanserin had no antihypertensive effect when measured 14 h after the last dose. The rise in blood pressure between 2 and 14 h after dosing was 11/4 mm Hg supine (P less than 0.01/NS) and 8/5 mm Hg standing (P less than 0.05/P less than 0.05). 4. The antihypertensive response to ketanserin was positively related to initial blood pressure and, independent of this, to age. It was not related to plasma concentrations of ketanserin or ketanserinol. 5. Five of 28 patients taking ketanserin discontinued treatment because of side-effects, compared with one of 28 patients taking placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894216 TI - Effects of fenoldopam, a specific dopamine receptor agonist, on blood pressure and left ventricular function in systemic hypertension. AB - 1. The effects of fenoldopam, an orally active, specific dopamine-1 receptor agonist, were studied in eleven patients with essential hypertension, using intra arterial blood pressure recording and equilibrium gated radionuclide angiography. 2. A single dose of fenoldopam 100 mg produced a fall in blood pressure (BP) starting after 20 min. The maximum BP reduction (23/25 mm Hg) occurred after 50 min and was accompanied by a heart rate (HR) increase of 10 beats min-1. The acute effects on BP lasted for 130 min. 3. After 8 weeks of fenoldopam 100 mg, twice daily, only a small, statistically insignificant, hypotensive effect was still apparent after each dose of drug. The duration of the effect was too short to be clinically useful. Tilt-testing produced a BP fall of 24/14 mm Hg and a HR increase of 17 beats min-1. Three patients experienced symptoms of postural hypotension during the study. 4. The drug attenuated the blood pressure rise produced by dynamic cycle exercise and isometric hand grip. 5. Acute administration of fenoldopam increased the left ventricular ejection fraction from 61% to 71% (P less than 0.005) and increased the peak filling rate from 2.52 to 3.86 end diastolic vol s-1 (P less than 0.002). After chronic fenoldopam administration, the left ventricular ejection fraction was 65% (P = NS) pre-dose, rising to 69% (P less than 0.02) post-dose and the peak filling rate was increased from 2.7 to 3.38 end diastolic vol s-1 (P less than 0.01) 60 min post dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894217 TI - The comparative effects of ICI 118551 and propranolol on essential tremor. AB - 1. The effects of the selective beta 2-adrenoceptor antagonist ICI 118551 on essential tremor, heart rate and blood pressure were compared with those of propranolol. 2. ICI 118551 (150 mg daily for 7 days) and propranolol (120 mg daily for 7 days) were about equally effective in reducing essential tremor (by about 40%) and were more effective than placebo. 3. When compared with the effect of placebo, propranolol reduced blood pressure and exercise heart rate whereas ICI 118551 had no significant effect on blood pressure and produced a small but significant reduction in exercise-induced tachycardia. 4. ICI 118551 may be useful in the management of essential tremor while having fewer cardiovascular side-effects than non-selective beta-adrenoceptor antagonists. PMID- 2894218 TI - Human orthostatic reflexes after taking temazepam at night. AB - 1. Cardiovascular orthostatic reflexes have been studied at night in 12 healthy male subjects who were given two soft gelatin capsules each containing 0 or 10 mg temazepam at 21.30 h. 2. The changes in heart rate, blood pressure and forearm blood flow on consecutive 5 min exposures to lower body negative pressure (suction) at 30, 40 and 50 mm Hg were measured before and then 1.5 and 9.5 h after giving doses of 10 or 20 mg temazepam in a placebo-controlled double-blind cross-over study. 3. Pre-suction resting values were not affected by temazepam, but 1.5 h after giving the capsules there were significant differences in the responses to suction between the placebo and 20 mg temazepam experiments: the tachycardia after 20 mg temazepam was about one-third greater and the forearm vasoconstriction was about 50% less. The effect of the 10 mg dose was equivocal. No residual effects were detected the next morning. 4. These alterations in orthostatic reflexes soon after the administration of temazepam at night did not impair the maintenance of arterial blood pressure in these healthy subjects. PMID- 2894221 TI - The clinical relevance of intrinsic sympathomimetic activity. Basel, August 28 29, 1986. Proceedings. PMID- 2894219 TI - Dipipanone and nifedipine in cold induced pain; analgesia not due to skin warming. AB - The mechanism of the pain relief produced by opiates in normal volunteers in the cold induced pain test has been investigated. In a double-blind placebo controlled study, hand skin temperature during a 3 min immersion in water at 1 degree C was not affected by either the opioid dipipanone 8 mg or the vasodilator nifedipine 10 and 20 mg. During this immersion, dipipanone produced significant pain relief. Nifedipine reduced pre-immersion blood pressures and raised heart rates, however, it did not significantly alter pain scores. It is concluded that vasodilatation and local warming do not play a role in the relief of pain by opiates in the cold immersion test. PMID- 2894220 TI - CSF concentrations of famotidine. PMID- 2894222 TI - Is the ISA of pindolol beta 2-adrenoceptor selective? AB - 1. Pindolol is a beta-adrenoceptor blocking drug with ISA (also called partial agonist activity). This means that in addition to blocking the effects of beta adrenoceptor agonists, it produces some stimulation of beta-adrenoceptors. 2. In vitro studies with pindolol show that its maximum stimulant action is similar to that of isoprenaline in tissues possessing mainly beta 2-adrenoceptors, but is negligible in tissues possessing mainly beta 1-adrenoceptors. This suggests selective stimulation of beta 2-adrenoceptors. 3. In man the arteriodilator effects observed after intra-arterially infused pindolol at concentrations within the same range as those producing an antihypertensive effect also suggest a stimulant action on vascular beta 2-adrenoceptors. 4. The fact that pindolol prevents the reduction of resting heart rate and cardiac output observed after drugs lacking ISA at first sight suggests stimulation of cardiac beta 1 adrenoceptors. However, human atria possess not only beta 1- but also beta 2 adrenoceptors, stimulation of which would produce the same effect. 5. Although all beta-adrenoceptor antagonists lower blood pressure, recent experiments have shown that those agents with combined beta 1-adrenoceptor blocking activity and ISA at those receptors are less effective. This observation lends weight to the thesis that pindolol does not stimulate beta 1-adrenoceptors since it lowers blood pressure as effectively as drugs lacking ISA. 6. The evidence available therefore suggests that although pindolol blocks both beta 1- and beta 2 subtypes, it selectively stimulates beta 2-adrenoceptors. PMID- 2894223 TI - Cardiac effects of beta-adrenoceptor blockade with intrinsic sympathomimetic activity during submaximal exercise. AB - 1. beta-adrenoceptor blocking agents with intrinsic sympathomimetic activity (ISA) are characterized by lesser depression of cardiac performance during low levels of sympathetic stimulation than beta-adrenoceptor blocking agents lacking ISA. Studies of the effects of ISA on cardiac output and on the determinants of myocardial oxygen demand during submaximal exercise are described and distinct differences between beta-adrenoceptor antagonists with and without ISA emerge. 2. At doses which produce similar effects on maximal exercise heart rate, and resting and exercise systolic blood pressure, pindolol, a beta-adrenoceptor blocking agent with substantial ISA, allows a higher submaximal exercise cardiac output and submaximal heart rate X systolic blood pressure product than does propranolol, a beta-adrenoceptor antagonist without ISA. 3. These findings may have clinical relevance in specific groups of patients such as those with arterial hypertension, where the preservation of cardiac function may allow for a more physiologic exercise response. Implications in patients with coronary artery disease and chronic heart failure await further study. PMID- 2894224 TI - Large arteries in hypertension: heterogeneous haemodynamic response to beta adrenoceptor antagonists with and without intrinsic sympathomimetic activity. AB - 1. Hypertension is associated with a distension of the large arteries and consequently a marked reduction in arterial compliance, which does not result merely from the mechanical effects of elevated arterial pressure but also from early functional and/or structural changes in the arterial walls. This suggests that one of the aims of antihypertensive therapy should be to reverse these arterial abnormalities in the hope of protecting the patient from the atherosclerotic complications of hypertension. 2. Studies have been carried out to compare the effects of equieffective antihypertensive doses of pindolol and propranolol on the arterial circulation in patients suffering from essential hypertension. After 3 months therapy pindolol produced a dilatation of the brachial artery with an increase in arterial compliance and blood flow. In contrast, propranolol, despite comparable antihypertensive effects, did not influence brachial artery circulation. 3. These different effects on the arterial circulation presumably reflect the differing pharmacological properties of the two beta-adrenoceptor antagonists and suggest that the intrinsic sympathomimetic activity of pindolol may be responsible for the qualitative differences in the arterial responses to the two drugs. 4. The results reviewed here reveal that even when two drugs of the same class are used to treat patients with essential hypertension the effects of these agents on arterial haemodynamics can vary greatly and are unrelated to the degree of blood pressure lowering. Thus, pindolol, in contrast to propranolol, not only lowers blood pressure but also reverses some of the changes in arterial haemodynamics which are characteristic of hypertensive disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894225 TI - Vasodilatation in hypertension: the relevance of ISA. Concluding paper. PMID- 2894226 TI - Structure and function of proton translocating ATPase in plasma membranes of plants and fungi. PMID- 2894227 TI - Somatostatin modulation of neurally mediated pepsinogen secretion from frog esophageal mucosa. AB - Frog esophageal mucosa contains peptic glands which are innervated by cholinergic neurons. When incubated in a medium containing 1.5 mM CaCl2, pepsinogen release from esophageal mucosa was increased by a high potassium concentration (55 mM KCl), 1,1-dimethyl-4-phenylpiperazinium (DMPP) or bethanechol. Whereas the response to bethanechol remained little changed, the response to high KCl concentrations or DMPP was abolished in the absence of Ca2+. The stimulatory effects of high KCl concentrations and DMPP were also eliminated by the presence of atropine or somatostatin. Furthermore, pepsinogen release in response to bethanechol was dose-dependently inhibited by somatostatin. Frog esophagus was found to contain somatostatin-like immunoreactivity, with a higher density at the end adjacent to the stomach. Chromatography of mucosa extract on Sephadex G-50 revealed a single peak of somatostatin-like immunoreactivity that coeluted with somatostatin-14. Immunohistochemical staining of the mucosa with peroxidase antiperoxidase technique demonstrated the presence of two varieties of somatostatin-like immunoreactivity-containing cells, one individually dispersed within the intercalated septa and the other in groups within the interlobular septa of the peptic glands. These results seem to indicate that somatostatin or somatostatin-like immunoreactivity may play a modulatory role in neurally mediated pepsinogen secretion in the frog esophagus. PMID- 2894228 TI - [Autogenic regulation of the sensitivity of liver cells to glucocorticoids during prolonged hormonal stimulation]. AB - The mechanisms of reversible decrease of hormone-dependent induction of tyrosine aminotransferase (TAT) by rat liver cells after prolonged administration of the glucocorticoid was studied. It was shown that the main links of the glucocorticoid action mechanism (i.e., the formation of a cytoplasmic hormone receptor complex and the hormone accumulation in the nuclei) do not change under these conditions. It was found also that one of the necessary prerequisites for the decrease of the hormone-dependent induction of TAT is the constant production by liver cells of large amounts of TAT irrespective of whether this process is induced by the glucocorticoid or by a non-hormonal inducer, e.g., tryptophan. Using the dot-hybridization technique, it was demonstrated that the inhibition of hormone-dependent induction of TAT is correlated with the reduction of mRNA TAT. It was supposed that the main links in the mechanism of inhibition of the hormone dependent induction are the formation of a large excess of the inducible protein- TAT--in the cells as well as the accumulation of end products of the TAT catalyzed transamination reaction which cause a feed-back repression of the de novo synthesis of TAT. Studies with cell cultures of Morris hepatoma which is known to be sensitive to glucocorticoids revealed the ability of glucose, the end product of gluconeogenesis reactions, to provide for selective inhibition of the hormone-induced accumulation of mRNA TAT in hepatoma cells. PMID- 2894230 TI - Autologous peripheral hematopoietic stem cell transplantation restores hematopoietic function following marrow ablative therapy. AB - From ten patients with advanced malignant disease involving the bone marrow, autologous hematopoietic stem cells were collected from the peripheral blood during eight four-hour pheresis procedures and cryopreserved. No manipulations to increase the number of stem cells circulating in the blood were used during the collections. Following marrow ablative chemotherapy or chemoradiotherapy, the autologous cells were thawed and infused intravenously (IV). WBCs reappeared in the circulation at a median of eight days (range seven to 11 days) after stem cell infusion. Two patients died early, whereas the other eight reached normal numbers of circulating granulocytes that have persisted for up to greater than 20 months. These eight patients became independent of RBC transfusions (hemoglobin concentration greater than 10 g/dL) at a median of 27 days (range 11 to 58 days) after transplantation. One patient received platelet transfusions for counts less than 50 x 109)/L, one patient developed a clinical picture of idiopathic thrombocytopenic purpura, and six patients maintained a platelet count greater than 20 x 10(9)/L at a median of 23 days (range 14 to 25 days) following stem cell infusion. This technique allows patients ineligible for autologous bone marrow transplantation due to unacceptable anesthetic risks, prior pelvic irradiation, or bone marrow metastases to receive marrow ablative therapy. PMID- 2894229 TI - An examination of the opiate receptor subtypes labeled by [3H]cycloFOXY: an opiate antagonist suitable for positron emission tomography. AB - 17-Cyclopropylmethyl-3,14-dihydroxy-4,5-alpha-epoxy-6-beta-fluoromorp hinan (cycloFOXY) is a fluorinated derivative of naltrexone suitable for labeling opiate receptors using positron emission transaxial tomography. Using the quantitative ligand binding method "binding surface analysis," in vitro autoradiography, and site-directed alkylating agents, [3H]cycloFOXY is shown to label mu and kappa opiate binding sites in vitro. Similar results were obtained using [3H]naloxone. Additional experiments demonstrate that [3H]cycloFOXY administered in vivo also labels mu and kappa binding sites. The relevance of these findings are discussed from clinical and basic science perspectives. PMID- 2894231 TI - [Study of anti-inflammatory endogenous mechanisms via the study of counter irritation]. PMID- 2894232 TI - United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: interim results. UK-TIA Study Group. AB - From 1979 to 1985, 2435 patients thought to have had a transient ischaemic attack or minor ischaemic stroke were allocated at random to receive long term blind treatment with either aspirin 600 mg twice daily (n = 815), aspirin 300 mg once daily (806), or placebo (814). Treatment continued with about 85% compliance until September 1986 (mean four years). The odds of suffering one or more of four categories of event--namely, non-fatal myocardial infarction, non-fatal major stroke, vascular death, or non-vascular death--were 18% less in the two groups allocated to receive aspirin than in the group allocated to receive placebo (2p = 0.01). The more relevant but less frequent composite event of disabling stroke or vascular death was reduced by only 7%; this reduction was not significantly different from zero, but nor was it significantly different from a 25% reduction. There was no definite difference between responses to the 300 mg and 1200 mg daily doses, except that the lower dose was significantly less gastrotoxic. PMID- 2894233 TI - Response to deoxycoformycin in T cell leukaemias. PMID- 2894234 TI - Early ontogeny of kappa-opioid receptor regulation of prolactin secretion in the rat. AB - Although both mu- and kappa-opioid components of prolactin (PRL) secretion have been identified in the adult rat, the neural pathways through which these multiple receptor subtypes modulate PRL secretion have not been thoroughly investigated. The present study utilizes the differential ontogeny of opioid systems which alter PRL release to examine the mechanisms by which mu- and kappa receptors regulate prolactin. The responses of PRL, corticosterone and growth hormone to opioid receptor subtype-specific agonists were studied in neonatal rats. The PRL response to the kappa-agonist, U50488, preceded the response to the mu-agonist, morphiceptin. Like adults, neonates demonstrated a growth hormone, but not a PRL, response to the delta agonist, [D-pen2,pen5]enkephalin. U50488 induced PRL secretion was not attenuated by cyproheptadine in adults or neonates, suggesting that the kappa-opioid mechanism operates independently of serotonin. In contrast, the PRL response to morphine was attenuated in adult rats. In addition, U50488 decreased median eminence dopamine synthesis in both adults and neonates. These findings suggest that the early developing, serotonin-independent opioid regulation of PRL is mediated through kappa-receptors, while the later developing mechanism which requires intact serotonergic transmission works through mu-receptors. kappa-Receptors appear to regulate PRL secretion by directly inhibiting the activity of tuberoinfundibular dopamine neurons, while mu receptors might regulate the tonic dopaminergic inhibition of PRL through a serotonergic pathway. PMID- 2894235 TI - Phorbol esters inhibit agonist-stimulated phosphoinositide hydrolysis in neuronal primary cultures. AB - The effects of phorbol esters on neurotransmitter-stimulated phosphoinositide (PI) hydrolysis in neurons in primary culture were investigated. Ten-day-old neuronal cultures were incubated with [3H]inositol for 2-3 days, exposed to phorbol esters, and the release of [3H]inositol phosphates was measured in the presence of 10 mM lithium. Pretreatment of the neuronal cultures with 1 microM phorbol myristate acetate (PMA) inhibited alpha 1, muscarinic, and glutamate receptor-mediated PI hydrolysis in a time-dependent manner with maximal inhibition observed after a 20-30 min preincubation. The active beta-phorbol didecanoate inhibited stimulated PI hydrolysis, but its stereo-isomer alpha phorbol didecanoate was without effect at 1 microM. PMA was about 10 times more potent at inhibiting PI hydrolysis stimulated by norepinephrine and glutamate compared to carbachol. The order of potency of the various phorbol esters for inhibition of stimulated PI hydrolysis and the differences between active and inactive stereoisomers suggests that the activation of protein kinase C may mediate the inhibitory effects. Thus, stimulation of neuronal protein kinase C may represent a mechanism for the regulation of agonist-stimulated PI hydrolysis. PMID- 2894236 TI - Stimulation-dependent phosphorylation of tyrosine hydroxylase in rat corpus striatum. AB - Incubation of rat corpus striatal synaptosomes with 32PO4 led to a time-dependent incorporation of 32P into tyrosine hydroxylase. Depolarization of the synaptosomes with elevated [K+]o increased 32P incorporation into tyrosine hydroxylase. The depolarization-dependent increase in 32P incorporation into tyrosine hydroxylase occurred rapidly (less than 15 sec), persisted in the presence of elevated [K+]o (up to 120 sec), required the presence of [Ca++]o, and was associated with serine (but not threonine or tyrosine) residues. After limit tryptic digestion of the 32P-tyrosine hydroxylase, several phosphopeptides were separated by HPLC, and elevated [K+]o increased 32P incorporation into two of these phosphopeptides. Thus, depolarization of dopaminergic terminals from the rat corpus striatum increased the phosphorylation of tyrosine hydroxylase, and the increase in phosphorylation appeared to occur at multiple sites. Multiple site phosphorylation of tyrosine hydroxylase has been previously shown in peripheral catecholaminergic tissues. However, substantial differences in the elution profiles of tyrosine hydroxylase phosphopeptides from striatal synaptosomes and from bovine adrenal chromaffin cells were observed. Thus, qualitative differences in the regulation of tyrosine hydroxylase may exist among the many catecholaminergic systems. PMID- 2894237 TI - Modulation of cerebellar granule cell activity by iontophoretic application of serotonergic agents. AB - Serotonergic fibers have been identified within the granule cell layer of the cerebellar cortex; however, their functional significance has not been identified. In this study the effect of serotonin on granule cell spontaneous activity was determined in the rat cerebellum. Of the 136 granule cells tested, 44.8% displayed a decrease in firing rate, 21.3% increased firing rate and 33.8% were not affected. The serotonin-induced changes in activity were not blocked by bicuculline or methysergide. The serotonin agonist 1,3 (trifluoromethylphenyl) piperazine mimicked the serotonin-induced suppressive response. Iontophoretically applied serotonin was also found to modulate GABA-induced suppression of granule cell activity. The variable effects of serotonin on spontaneous activity suggests the presence of more than one type of serotonergic receptor in the cerebellar granule cell layer. PMID- 2894238 TI - Topographic relations of cholinergic and noradrenergic neurons in the feline pontomesencephalic tegmentum: an immunohistochemical study. AB - The immunohistochemical localization of the neurotransmitter synthesizing enzymes choline acetyltransferase, tyrosine hydroxylase and dopamine-beta-hydroxylase was examined in the feline pontomesencephalic tegmentum. Examination of adjacent sections stained for either choline acetyltransferase, tyrosine hydroxylase or dopamine-beta-hydroxylase immunoreactivity, as well as individual sections doubly stained for both choline acetyltransferase and tyrosine hydroxylase immunoreactivity, unequivocally demonstrated that noradrenergic and cholinergic neurons were extensively intermingled in the brainstem tegmentum of the cat. This contrasts with the situation in various other species, where neurons utilizing these two neurotransmitters are discretely localized in distinct nuclei. Furthermore, the present studies demonstrate the existence of two types of choline acetyltransferase immunoreactive neurons in the feline tegmentum: the magnocellular neurons of the pedunculopontine and laterodorsal tegmental nuclei which stain histochemically for NADPH diaphorase, plus a population of small spindle-shaped neurons in the medial and lateral parabrachial nuclei which do not stain positively for NADPH diaphorase. The data are discussed with respect to several influential hypotheses of sleep cycle control. PMID- 2894240 TI - Effects of 3-aminobenzamide on the induction of gamma-glutamyl-transpeptidase positive foci by various chemicals in rat liver. AB - The effects of 3-aminobenzamide (ABA), a representative inhibitor of poly(ADP ribose)polymerase, on the induction of gamma-glutamyl-transpeptidase (GGT) positive foci, an early lesion occurring during hepatocarcinogenesis, in rat liver by various chemicals were studied in Fischer 344 and Wistar rats. ABA exhibited an enhancing effect on the induction of GGT-positive foci by benzo[a]pyrene, but no effects on induction by a methylating agent, N-methyl-N nitrosourea, in both rat strains. In contrast, the induction of GGT-positive foci by another methylating agent, 1,2-dimethylhydrazine, was enhanced by ABA in Wistar rats, but not affected in Fischer rats. There were no effects of ABA on the induction of GGT-positive foci by N-bis(2-hydroxypropyl) nitrosamine in Wistar rats. These results indicate a differential effect of ABA on the induction of GGT-positive foci by different chemicals in different rat strains. PMID- 2894239 TI - Radioiodinated meta-iodobenzylguanidine uptake in medullary thyroid cancer. A French cooperative study. AB - Fifty meta-iodobenzylguanidine (MIBG) scintiscans were performed in three groups of medullary thyroid cancer (MTC) patients. Group 1 (n = 11) included treated patients with normal calcitonin levels; Group 2 (n = 24) included patients with elevated calcitonin levels due to sporadic and isolated MTC; Group 3 (n = 15) included patients with elevated calcitonin levels due to familial MTC or multiple endocrine neoplasia Type IIA syndrome (MEN). In Group 1 three pheochromocytoma were depicted by MIBG scintiscan. In Group 2 MTC was seen in a small number of patients (3 of 24). In Group 3, besides adrenal hyperplasia and pheochromocytoma four patients, MIBG scintigraphy showed where MTC had localized and spread in almost half of patients (7 of 15). MIBG uptake occurred in patients with relatively high calcitonin level (greater than 0.6 nmol/l). These data indicate that in patients with familial MTC or MEN syndrome, MIBG scintiscan can be useful not only in detecting associated pheochromocytoma, but also in showing MTC. PMID- 2894241 TI - Contribution by host tissues to circulating glutamine in mice inoculated with Ehrlich ascites tumor cells. AB - Twenty-four h after tumor transplantation increases of free glutamine in plasma, liver, and kidney occurred simultaneously with the exponential phase of tumor growth. Kidney and muscle glutamine synthetase also increased in the first 2 days following tumor transplantation, while kidney and liver glutaminases decreased. The levels of free glutamine in plasma and tissues, and the activities of glutamine synthetase and glutaminase, tended to approach normal values in the last days of life of the tumor-transplanted animals. Eleven days after transplantation, liver glutamine synthetase activity diminished. The results are discussed in terms of a glutamate/glutamine intercellular cycle which could augment the circulating glutamine, the main source of nitrogen for tumor cells. PMID- 2894242 TI - Expression of the c-raf protooncogene, gamma-glutamyltranspeptidase, and gap junction protein in rat liver neoplasms. AB - Female Harlan Sprague-Dawley and F-344 rats were subjected to a 70% hepatectomy and 18 h later given one dose of 30 mg diethylnitrosamine/kg body weight. Beginning 1 week later, the animals were fed a diet containing 0.05% phenobarbital. Groups of rats were sacrificed 6 and 15 months later, and the livers were either frozen for cryostat sectioning or used to isolate RNA. Primary liver tumors present in these animals were used for RNA isolation, and a portion was taken for histopathological analysis. Eleven of 13 primary lesions, consisting of either neoplastic nodules or hepatocellular carcinomas, showed elevated levels of mRNA for the c-raf protooncogene. Increased c-raf mRNA in these tumors appeared to be unrelated to their cellular proliferative status inasmuch as the levels of c-raf mRNA did not correlate with levels of H4 histone mRNA. Decreased expression of the major rat liver gap junction protein mRNA was observed in all of the primary tumors. Immunocytochemical analysis using an anti gap junction antibody revealed a decrease in gap junction immunoreactivity in some but not all preneoplastic focal lesions. All preneoplastic foci having positive gamma-glutamyltranspeptidase enzyme staining also exhibited a marked increase in gamma-glutamyltranspeptidase mRNA as determined by in situ hybridization. The possible relation of alterations of the mRNA levels of c-raf and the gap junction protein to the further development of preneoplastic foci is discussed. PMID- 2894243 TI - Opioid analgesics. PMID- 2894245 TI - Tolerability of timolol and betaxolol in patients with chronic open-angle glaucoma. AB - Twenty-four patients with bilateral chronic open-angle glaucoma received three treatments: (1) artificial tears (control) in both eyes, (2) artificial tears in one eye and one drop of timolol (0.05%) in the other, and (3) artificial tears in one eye and one drop of betaxolol (0.05%) in the other. Twelve patients always received the test medication in the left eye and 12 in the right eye. The patients were examined and questioned about ocular symptoms at the time of drug administration and at 1, 5, 30, and 60 minutes. Irritation was noted in five treated eyes after artificial tears, in three after timolol, and in 11 after betaxolol. The incidence of irritation after initial treatment was significantly lower than expected for timolol than for artificial tears or betaxolol (P less than 0.01). PMID- 2894244 TI - Effects of prolonged oral cimetidine, ranitidine, and famotidine therapy on antipyrine elimination. AB - The effects of three histamine H2-receptor antagonists on the antipyrine metabolizing capacity of the liver were studied in 32 patients with gastrointestinal disorders and in three healthy volunteers. The drugs studied were 800 mg and 400 mg of cimetidine, 300 mg of ranitidine, and 40 mg of famotidine daily. Only cimetidine at 800 mg/day inhibited hepatic antipyrine metabolism, and the inhibitory effects disappeared rapidly with no accumulation. PMID- 2894246 TI - Effects of nipradilol, a new beta-blocking agent with vasodilating properties, on exercise tolerance in patients with stable effort angina: a double-blind study. AB - The effects of nipradilol, a new beta-blocking agent with vasodilating properties, on exercise tolerance were examined in eight patients with stable effort angina. Symptom-limited treadmill tests were performed two hours after administration of oral nipradilol (9 mg) or placebo in a double-blind manner. Exercise time to the onset of angina was significantly longer after nipradilol than after placebo (6.8 +/- 2.5 min versus 5.0 +/- 1.2 min, P less than 0.05). Exercise duration after nipradilol was not statistically different from that after 0.3 mg of sublingual nitroglycerin (7.2 +/- 1.9 min). Nipradilol significantly decreased heart rate both at rest and during exercise (P less than 0.01). Systolic blood pressure at rest did not change after nipradilol. However, an increase in systolic blood pressure during exercise was inhibited by nipradilol. The pressure rate product was significantly lower after nipradilol than after placebo. It is concluded that nipradilol improves exercise tolerance in patients with stable effort angina by decreasing the myocardial oxygen consumption during exercise. PMID- 2894247 TI - Regional fat loss from the thigh in obese women after adrenergic modulation. AB - Beta-adrenergic stimulation and alpha 2-adrenergic inhibition increase lipolysis from fat cells. Twenty-eight obese women were placed on a calorie-restricted diet and one of five treatments was applied to one thigh three to five times per week for four weeks: (1) isoproterenol injections; (2) cream containing colforsin (forskolin), aminophylline, and yohimbine; (3) yohimbine cream; (4) colforsin cream; or (5) aminophylline cream. The opposite thigh was treated with a placebo (injection or cream). The treated thighs lost significantly more girth after treatment, both by injection and by cream. No adverse reactions were attributable to either the cream or the injections. It is concluded that local fat reduction from the thigh can be safely accomplished. PMID- 2894248 TI - Ultracytochemical localization of guanylate cyclase and adenylate cyclase in rat small intestine. PMID- 2894249 TI - Aminergic and peptidergic amplification of intracellular cyclic AMP levels in a molluscan neural network. AB - 1. Serotonin (5-hydroxytryptamine; 5-HT), dopamine (DA), and small cardioactive peptide B (SCPB) can activate adenylate cyclase and increase the intracellular cyclic AMP (cAMP) levels in the Limax procerebrum (PC), with differing time courses and to differing extents. 5-HT and SCPB are potent stimulators of adenylate cyclase, and when both were applied simultaneously, an additive effect was observed. 2. In contrast, DA shows a great variability in the time course of cAMP synthesis and is a weak stimulator. Ergonovine, a DA antagonist, failed to inhibit cyclase activation, indicating that ergonovine-sensitive receptors are absent or ergonovine-sensitive DA receptors are not coupled to adenylate cyclase. 3. 5-HT and SCPB cause a rapid synthesis of cAMP, reaching the maximum 20- to 30 fold increase within a minute. DA's effect is slow in onset and very prolonged, reaching a maximum of only a two- to three-fold increase in the cAMP level. Reasons for variability in DA action are discussed. PMID- 2894251 TI - UASs and enhancers: common mechanism of transcriptional activation in yeast and mammals. PMID- 2894250 TI - Proliferation, senescence, and neoplastic progression of beta cells in hyperplasic pancreatic islets. AB - Three different cases of pancreatic beta cell hyperplasia in mice are accompanied by an increase in a subclass of cells expressing tyrosine hydroxylase (TH), a neuronal enzyme. In the nontumorigenic cases of islet growth during normal pregnancy and in the obese mutant mouse, the TH-insulin cells do not divide, in contrast to the "insulin-only" cells. In later stages the number of proliferating insulin-only cells decreases concomitant with an increase in the number of nondividing TH-insulin cells, suggesting that the TH-insulin cells are on a pathway to senescence. In the presence of an oncoprotein the TH-insulin cells are able to proliferate. The proliferation of this cell type may represent an escape from the senescence pathway and progression to immortal tumor cells. PMID- 2894252 TI - TAP transcription and phosphatidylinositol linkage mutants are defective in activation through the T cell receptor. AB - TAP is a phosphatidylinositol-anchored membrane protein that is involved in murine T lymphocyte activation. To determine the relationship between TAP and T cell receptor/CD3-mediated activation, we derived TAP expression mutants of a T-T hybridoma. Two phenotypically distinct classes of mutants were obtained. The first has a selective defect in the transcription of TAP, while the second has a defect in the biosynthesis of phosphatidylinositol-protein linkages. Both mutations affect antigen-stimulated, T cell receptor-mediated activation of the T T hybrid. These variants have intact immune effector gene programs, as they are responsive to pharmacologic agents that mimic receptor signals. These findings support a role for phosphatidylinositol-linked cell-surface glycoproteins in physiologic T cell activation. Consistent with this interpretation, we observed similar defects in T cell responsiveness after enzymatic removal of phosphatidylinositol-linked proteins from normal T lymphocytes. PMID- 2894254 TI - Qualitative and quantitative heterogeneity in Pgp-1 expression among murine thymocytes. AB - A proportion of Pgp-1+ cells in the thymus have been shown to have progenitor activity. In adult AKR/Cum mice the total Pgp-1+ population in the thymus differs from that of the bulk of thymocytes and is antigenically heterogeneous when examined by flow cytometry. Pgp-1+ thymocytes are enriched for several minor cell populations compared to total thymocytes: B2A2-, interleukin-2-receptor+ (IL 2R+), and Lyt-2-, L3T4-. However, these subsets are still a minor proportion of the Pgp-1+ cells, the majority being Lyt-2+ and/or L3T4+ and B2A2+. Pgp-1+ thymocytes also differ from the bulk of thymocytes in having lower amounts of Thy 1 and in showing a higher proportion of single positive (Lyt-2+, L3T4- or Lyt-2-, L3T4+) cells. Populations of adult thymocytes that are enriched in progenitor cells can be isolated by cytotoxic depletion using either anti-Thy-1 antibody (Thy-1 depletion) or anti-Lyt-2 and anti-L3T4 antibody (Lyt-2, L3T4 depletion). Pgp-1+ cells in progenitor cell-enriched populations are also phenotypically heterogeneous. Pgp-1+ cells in both populations may be IL-2R+ or IL-2R- and B2A2+ or B2A2-. The population of Pgp-1+ cells in progenitor cell-enriched populations in the adult differs from that of the fetus at 14 days of gestation in that in the 14-day fetus, most Pgp-1+ cells are IL-2R+. By Day 15 of gestation, distinct populations of Pgp-1+, IL-2R-; Pgp-1+, IL-2R+; and Pgp-1-, IL-2R+ cells are observed. In the 15-day fetus, as in the adult, many Pgp-1+ thymocytes express low to moderate levels of Thy-1. The total percentage of Pgp-1+ cells in the thymus varies among different mouse strains, ranging from 4 to 35% in the thymus of young adult mice. Pgp 1.1 strains contain more detectably Pgp-1+ thymocytes than Pgp 1.2 strains; however, there is variability in the proportion of Pgp-1+ cells, even among Pgp 1.2 strains. In contrast to AKR/Cum mice, the Pgp-1+ thymocyte population in BALB/c mice, which contain a high proportion of Pgp-1+ thymocytes, closely resembles the total thymocyte population. PMID- 2894255 TI - [Tissue culture of Corydalis yanhusuo and alkaloid production]. PMID- 2894253 TI - Guinea pig and gerbil erythrocytes rosette with different cells in the blood, bone marrow, and thymus of the cat. AB - Cat thymocytes, bone marrow cells, and peripheral blood leukocytes (PBL) formed rosettes with guinea pig (GP) and gerbil (G) erythrocytes (E). In PBL from adult cats the frequency of rosettes was 27% with GPE and GE, while an average of 33% bone marrow cells formed rosettes with GPE and only 4% with GE. Thymocytes from kittens showed a high percentage of rosettes with both GPE and GE (35 to 81%), with the frequency of each type varying with the thymus tested. Fluorescein isothiocyanate labeling of one of the erythrocyte species revealed these cells to be rosetting with different nucleated cells; i.e., a low percentage (3-5%) of the rosettes formed with PBL and bone marrow had both labeled and unlabeled erythrocytes. In contrast, "mixed" rosettes were observed with a significant number of thymocytes, averaging 33% of thymocytes from six animals. A further distinction between the GE- and GPE-rosetting cells was revealed by a monoclonal antibody which blocked GE rosette formation without interfering with the binding of GPE to PBL and thymocytes. PBL could be depleted of either GPE- or GE rosetting cells, with retention of IgG+ cells and cells capable of rosetting with the second erythrocyte species in the nonrosetting fractions. Stimulation of the latter nonrosetting fractions with pokeweed mitogen for induction of Ig synthesis revealed a T-lymphocyte specificity of the GE- and GPE-rosetting cells. PBL depleted of GE-rosetting cells yielded an increased Ig production, two- to threefold above the control; in contrast, depletion of GPE-rosetting cells from PBL resulted in a failure of the remaining cells to respond. These results suggest that T-suppressor cells of the cat are contained in the GE-rosetting fraction and T-helper cells are rosetted with GPE. PMID- 2894256 TI - [Lymphatic filariasis in Vanuatu]. AB - Lymphatic filariasis, in the Archipelago of Vanuatu, is due to Wuchereria bancrofti. The vector is Anopheles farauti, endophilic mosquito, which transmits also malaria. The level of endemicity was very high in the beginning of this century (microfilariae in blood: 60.9%, elephantiasis: 21%), and has dramatically decline now by detection and treatment of sick people (70 cases in 1986), mass chimioprophylaxis and protection against the vectors. But these actions must be continued to obtain the eradication of filariasis in the Vanuatu. PMID- 2894257 TI - Comparative histochemical investigation of the glutathione S-transferase placental form and gamma-glutamyltranspeptidase during N-nitrosobis(2 hydroxypropyl)amine-induced lung carcinogenesis in rats. AB - Immunohistochemical staining using anti-rat glutathione S-transferase placental form (GST-P) rabbit antibody and enzyme histochemical staining for gamma glutamyltranspeptidase (gamma-GT) were investigated in lesions appearing during lung carcinogenesis induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats. Rats were given BHP at a concentration of 2000 p.p.m. in drinking water, and were killed after 12 weeks of BHP intake, after 12 weeks of BHP intake followed by 12 weeks of tap water intake or after 20 weeks of continuous BHP intake. It was found that bronchiolo-alveolar hyperplasias, adenomas, adenocarcinomas, squamous metaplasias and squamous cell carcinomas had been induced by BHP. All of the squamous metaplasias and squamous cell carcinomas were shown to stain with GST-P but not with gamma-GT. On the other hand, the hyperplasias, adenomas and adeno carcinomas stained with gamma-GT to various degrees and in different areas, but did not stain with GST-P. The incidence of gamma-GT phenotype and the average percentage of gamma-GT-positive areas in hyperplasias and adenomas suggested that adenocarcinomas might develop from hyperplasias and adenomas. These results suggest that GST-P is a marker for squamous lesions while gamma-GT is a marker for adenomatous lesions in rat lung carcinogenesis. Furthermore, squamous metaplasias appear to be preneoplastic lesions of squamous cell carcinomas while gamma-GT-positive hyperplasias or adenomas are preneoplastic lesions of peripheral adenocarcinomas. PMID- 2894259 TI - Arylsulfatase A in urine of patients with urothelial tumors. AB - A significant increase in urine arylsulfatase A activity (p less than 0.01) was found in patients with urothelial tumors. Arylsulfatase A activity was 1.36 +/- 1.10 U/24-h urine in control specimens, 1.90 +/- 1.66 U/24-h urine in various genitourinary tract disorders, and 3.90 +/- 1.98 U/24-h urine in transitional cell carcinoma specimens. Surgical treatment of the neoplastic patients lowered the arylsulfatase A activity found in urine to within reference values. The arylsulfatase A excreted by patients with these tumors was highly sensitive to thermal inactivation while the enzyme activity in the control urines was less affected by the heat treatment. The time course of the arylsulfatase A reaction with 4-nitrocatechol sulfate was not linear in normal individuals, while it was linear in 90% of patients with urothelial tumors. This difference in the kinetic pattern of the enzyme could be used to increase the diagnostic specificity of the determination. PMID- 2894258 TI - Quality control material for activity determinations of urinary enzymes. AB - We examined the stability of N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30), alanine aminopeptidase (EC 3.4.11.2), alkaline phosphatase (EC 3.1.3.1), gamma glutamyltransferase (EC 2.3.2.2), and lysozyme (EC 3.2.1.17) in urine prepared by gel filtration and supplemented with albumin, or ethylene glycol, or ethylene glycol plus albumin during storage at -20 degrees C for a period of 12 months. The stability was assessed by linear regression analysis of monthly values versus time. All enzymes except for gamma-glutamyltransferase could be considered stable for about one year in all three control materials provided that maximum change of 10% of the starting enzyme activity is accepted as tolerable. If ethylene glycol is used as stabilizer, its suitability must be tested and its inhibitory effect on enzyme activities must be taken into account in intermethod comparisons, because in some methods, it may be removed in a pretreatment step. PMID- 2894260 TI - Takayasu's arteritis and mitral stenosis. AB - A 44-year-old housewife was found to have coarctation of the abdominal aorta secondary to Takayasu's arteritis. Since she also had mitral stenosis, possible etiological relation between Takayasu's arteritis and mitral stenosis is suspected. PMID- 2894261 TI - Arm exercise testing for coronary artery disease in patients with peripheral vascular disease. AB - We evaluated 74 peripheral vascular disease (PVD) patients (54 men, age 61 +/- 7 years and 17 women, age 63 +/- 7 years) for potential coronary heart disease (CAD) using an arm exercise test (AET) protocol. All patients performed upright two-arm cranking using discontinuous stages of 2 minutes of exercise separated by 2 minutes of rest. Exercise intensity was increased by +100 or 200 kpm (kilopond meters) with each stage. ECG was monitored continuously and blood pressure and 12 lead ECG tracings were obtained at the end of each exercise stage. All patients reached an endpoint of subjective exhaustion. Men achieved 91 +/- 14% of age predicted heart rate at 597 +/- 167 kpm, while women achieved 86 +/- 14% of age predicted heart rate at 335 +/- 117 kpm. Ischemic ECG responses (+AET) defined as new or additional ST depression greater than 1.0 mm X 80 ms, occurred in 35 men (65%) and 7 women (42%). Coronary angiography was performed in a subset of 22 patients (15 males and 7 females). CAD (greater than 70% stenosis) was found in 11 of 12 men and 4 of 5 women who showed positive or strongly positive AET responses (overall predictive value for AET = 88%). We conclude that arm exercise stress testing is safely performed in PVD patients who cannot complete treadmill exercise. In this limited series of PVD patients, the predictive value of a +AET response for diagnosis of CAD is similar to established values for treadmill exercise. PMID- 2894262 TI - [A case of adult T-cell leukemia showing diffuse periventricular lesions with contrast enhancement in cerebral computed tomography]. PMID- 2894263 TI - [A case of HTLV-I associated myelopathy (HAM)--an immunological aspect]. PMID- 2894264 TI - HLA-D region RFLPs indicate that susceptibility to insulin-dependent diabetes in South India is located in the HLA-DQ region. AB - Recently close markers for insulin-dependent diabetes mellitus in Western 'Caucasoid' subjects have been defined from DQ region (both alpha and beta genes) restriction fragment length polymorphisms. In order to define the genetic contribution to insulin-dependent diabetes mellitus in an Indian population we have analysed 58 unrelated Dravidian (South Indian) insulin-dependent diabetic patients and 43 controls. In insulin-dependent diabetes an increased frequency of the Taq 1 DQ beta restriction fragment length polymorphisms designated T2 omega/T6 (relative risk = 10.6), and of homozygotes for Taq 1 DQ alpha 4.6 kb (relative risk = 11), was found in the patients. The highest relative risk for insulin-dependent diabetes mellitus was obtained by comparing patients and control subjects who either (a) co-inherited DQT2 omega/T6 with certain DQ alpha restriction fragment length polymorphisms or (b) were DQ alpha 4.6 kb homozygotes, the combination of (a) and (b) accounting for 55.5% of insulin dependent diabetes mellitus subjects and none of the controls (relative risk = 101; 95% confidence limits 93-109). PMID- 2894265 TI - Cytochromes P-450. AB - 1. The cytochromes P-450 are of interest in fields as diverse as biochemistry, pharmacology, mechanistic and synthetic chemistry, carcinogenesis, toxicology, endocrinology, and nutrition. 2. Cytochrome P-450 enzymes are coded by a multi gene family. 3. The many forms have some elements of similarity in their primary sequences and catalyze chemically equivalent reactions, either mixed-function oxidations or reductions. 4. The catalytic specificity of the individual forms of the enzyme is related to three-dimensional interactions between individual substrates and their binding sites, and the reactions are related in their chemistry. 5. Regulation of enzyme levels appears to involve transcriptional and post-transcriptional aspects. PMID- 2894267 TI - Proctolin potentiates synaptic transmission in the central nervous system of an insect. AB - 1. Bursts of spike activity in the ventral nerve cord of the cockroach were elicited by mechanically stimulating the cercal organs. 2. In the presence of micromolar proctolin, the peak frequency and the duration of a burst were slowly but significantly increased. 3. In contrast, carbachol produced an immediate enhancement of spontaneous activity, but a potentiation of bursts was not seen. 4. It is proposed that proctolin functions as a neuromodulator in the terminal abdominal ganglion of the cockroach. PMID- 2894266 TI - Sympathetic innervation of the rectum and bladder of the skate and parallel effects of ATP and adrenalin. AB - 1. Longitudinal muscles of the rectum of the skate are first briefly excited and then inhibited by stimulation of the sympathetic nerve fibres. 2. ATP, adrenalin and noradrenalin also produce inhibition. 3. 5HT is strongly excitatory but acetylcholine is only excitatory above 1 microM. 4. The rectum contracts strongly to mechanical stimulation; the response is not blocked by TTX. 5. The inhibitory actions of sympathetic stimulation or ATP were not blocked by guanethidine, propranalol, antazoline, theophylline or bee venom (apamin). 6. ATP continued to produce inhibition after the nerve response was blocked by TTX. 7. The urinary bladder gives slow rhythmic contractions, which are inhibited by nerve stimulation and by adrenalin but ATP has no action. 8. 5HT is strongly excitatory but acetylcholine has little action. PMID- 2894268 TI - Characterization of nicotine-induced contraction in the canine bronchus. AB - 1. The modes of action of nicotine on the dog bronchial smooth muscle preparation was investigated, in order to compare with those on the bronchial preparations from the guinea-pig, rabbit and monkey. 2. Nicotine induced a contraction in the dog bronchial preparation, and this response was abolished by hexamethonium and atropine and potentiated by physostigmine. 3. These findings suggest that the contractile response to nicotine was mediated through an action on the nicotinic receptors and due to the release of acetylcholine. 4. Tetrodotoxin did not inhibit the contractile response to nicotine in the dog bronchial preparation, suggesting that the nicotine-induced response may be produced mainly through a sodium action potential-independent process. 5. The present observations in the dog bronchial preparations coincided with those in the rabbit and monkey bronchi but not with the findings in the guinea-pig bronchus. PMID- 2894269 TI - Differential effects of adrenergic blockade on seasonal changes in core temperatures and thermal conductances of deer mice maintained in thermal neutral environments. AB - 1. Resting, daytime, thermal conductances and metabolic rates of mice conditioned to winter (10:14LD) and summer (14:10LD) photoperiods were reduced by social huddling; huddling resulted in group size related elevations in core temperature during summer, but not with winter light-dark cycle exposures. 2. Core temperatures of resting, solitary winter animals were lower than those of summer; both summer and winter animals' core temperatures were further reduced by increased thermal conductance resulting from (phentolamine) alpha receptor blockade. 3. Social huddling reduction of the heat loss from phentolamine treatment was more effective for winter (10:14LD) animals. 4. While phentolamine treatment resulted in increased thermal conductance and lower core temperatures of the mice, propranalol treatment resulted in lower core temperatures and resting metabolic rates, with a resulting decrease in thermal conductance. 5. Since adrenergic blockade was less dose-effective on winter animals, we reasoned that winter animals display higher levels of endogenous adrenergic capacity than summer animals and that lower winter thermoregulatory set points provide for energy conservation with enhanced capacity for meeting cold challenge. PMID- 2894270 TI - Behavioural observations and neurophysiological responses of cockroaches envenomated with Latrodectus katipo venom. AB - 1. The behaviour of American cockroaches envenomated with Latrodectus katipo venom was correlated with neurophysiological events recorded from an isolated cockroach CNS preparation to which venom was applied. 2. The injection of a venom extract into cockroaches caused convulsions (3 behavioural categories: quivering, jerking and hyperextension) which eventually led to paralysis and death. 3. Changes in the spontaneous activity of nerve 5 (from the metathoracic ganglion) corresponded to the time course of envenomation behaviours. An initial increase in discharge peaked 5-10 min after application and subsequently decreased to become irreversibly blocked. PMID- 2894271 TI - Hematological effects of ethyl methanesulfonate, paraquat and phenylhydrazine in Japanese quail. AB - 1. Juvenile Coturnix coturnix japonica males were injected intravenously with 2, 20 or 200 mg ethyl methanesulfonate (EMS)/kg body wt; 0.2, 2 or 20 mg paraquat (PARA)/kg body wt; or 0.6, 6 or 60 mg phenylhydrazine (PHZ)/kg body wt; and hematologic variables were measured at 0 (non-injected), 24 and 72 hr post injection. 2. EMS, PARA and PHZ-induced hemolytic anemia began within 24 hr post injection. 3. Recovery from anemia began within 72 hr post-injection of EMS or PARA, but PHZ injected quail continued to show a marked anemia at that time. 4. EMS and PARA induced lymphocytopenia, monocytopenia and heterophilia, while PHZ induced lymphocytosis, monocytopenia and heteropenia after injection. 5. These results suggest that the anemia induced by EMS and PARA was dissimilar from that induced by PHZ, that all chemicals affected leukopoiesis and that Japanese quail can mount a marked recovery from the hematologic affects of PARA, a widely used herbicide, in a short interval after intoxication. PMID- 2894273 TI - Changes in monoamine oxidase activity by mitochondria isolated from late embryos of Bufo bufo. AB - 1. Monoamine oxidase activity has been assayed in mitochondria isolated from post neural embryos (stages 14-25) of Bufo bufo, using 5-HT and PEA as substrates. 2. Mitochondria isolated from stages 19 to 25 show an increasing ability in deaminating monoamines, PEA being metabolized at a higher level with respect to 5 HT. 3. At all the examined stages 5-HT is metabolized by an enzyme corresponding to MAO A, while PEA, from stage 19, is largely deaminated by a semicarbazide sensitive amine oxidase (SSAO). 4. The effect of Triton X-100 on MAO A activity appears remarkably different in mitochondria isolated from embryos at stages 14 and 25 respectively. PMID- 2894272 TI - Effects of nicorandil on isolated smooth muscle cells from guinea-pig taenia caeci. AB - 1. The effects of nicorandil on guinea-pig taenia caeci were investigated with the use of isolated smooth muscle cells and glycerin-treated muscle fiber bundles. 2. Nicorandil inhibited high K-, Ca2+- and carbachol-induced contractions in a dose-dependent manner without affecting 45Ca fluxes in isolated cells. 3. Nicorandil had no effect on ATP-induced contraction of glycerin-treated muscle fiber bundles. 4. The present results suggest that nicorandil may inhibit the contraction by action on the contractile proteins in an indirect manner in guinea-pig taenia caeci. PMID- 2894274 TI - Effects of temperature oscillations on the distribution of 65Zn on cytoplasmic proteins. AB - 1. Oscillating temperatures cause an increase in 65Zn uptake into the digestive gland of M. edulis when compared with the effects of constant temperatures. 2. The increased uptake is associated with a change in the distribution of 65Zn onto cytoplasmic proteins. There is a fall in the percentage of metal on the greater than 70 K dalton fraction and a rise in the 3 K dalton fraction. 3. A possible hypothesis is produced to explain these effects in terms of heat lability of metal-protein ligands. PMID- 2894275 TI - Presynaptic alpha-adrenoceptor regulation of transmitter release in the conscious rat. AB - 1. Blood pressure (BP) and heart rate (HR) were recorded in conscious, adrenal demedulated rats. The rats were subjected to a 1-min period of mild "stress", induced by jet-air directed into the experimental cage. The plasma content of noradrenaline (NA), dopamine (DA) and 3, 4-dihydroxy-phenylacetic acid (DOPAC) was determined 1 min after termination of "stress". 2. The presynaptic alpha 2 adrenoceptor antagonist yohimbine (YOH) (10(-7) - 10(-6) mol/kg, given 5 min prior to "stress") did not alter the increase in BP and HR, induced by "stress", when compared to control rats (receiving NaCl instead of YOH at the corresponding time). 3. Pre-treatment with atropine (ATR) (2.5 mg/kg) 5 min before YOH (10(-6) mol/kg) or NaCl increased HR but not BP significantly in both groups of rats. "Stress", as above, gave a significant prolongation of the increase in HR in rats receiving YOH, when compared to control rats. The increase in BP was not significantly altered, compared to controls. 4. The neuronal re-uptake inhibitor desmethylimipramine (DMI) (0.1 mg/kg) was given together with ATR (2.5 mg/kg) 5 min before YOH (10(-6) mol/kg) or NaCl in one group of rats. This treatment induced a significant increase in HR but did not affect BP. "Stress", induced as above, extended the duration of the increase in HR in the YOH-treated rats, compared to controls. The increase in BP was not significantly different between the YOH-treated rats and the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894276 TI - Slow sodium-free contractures in the frog heart mediated by the sodium-calcium exchange. AB - 1. Sodium-free contractures were studied in myocardial strips from R. pipiens when extracellular sodium (Na+o) was replaced by choline chloride and extracellular free calcium (Ca2+o) was defined with EGTA-buffer. 2. Resting membrane potentials (RMP) were normal in sodium-free solutions with Ca2+o calculated below 1.0 x 10(-9) mol/l. 3. When Ca2+o was subsequently increased from zero to 1.0 x 10(-3) mol/l Na+-free contractures developed slowly with unchanged RMP even at maximum contracture, at which the intracellular ultrastructure is grossly altered. 4. The contractures developed significantly faster in the presence of 3 x 10(-6) mol/l ouabain. 5. In sodium-free solutions La3+ did not influence Ca2+-dependent contractures, apart from causing an increase in time to maximum contracture. 6. It is concluded that sarcolemmal integrity is maintained in frog myocardium treated initially with Na+/Ca2+-free solutions and then with Na+-free medium containing 1 mmol/l Ca2+. 7. Our experiments indicate that sodium-free, Ca2+o-dependent contractures are mediated by the Na+/Ca2+-exchange, operation at higher rates when Na+i is increased. La3+ (1 mmol/l) probably does not compete with Ca2+ at extracellular binding sites of the exchanger. 8. The Na+/Ca2+-exchange may under certain experimental conditions be able to increase Ca2+i to cytotoxic concentrations. PMID- 2894277 TI - Sodium-free contractures in frog myocardium damaged by catecholamines. AB - 1. Sodium-free contractures were studied in myocardial strips from R. pipiens with extracellular sodium (Na+o) replaced by choline chloride and extracellular calcium (Ca2+o) varied with EGTA-buffer. Normal myocardium was compared with that damaged by adrenaline (ADR) or isoproterenol (ISO). 2. Frog myocardium, damaged by in vivo injections of catecholamines, remained relaxed when exposed to Na+/Ca2+-free solutions. Only in 2 out of 18 experiments were small contractures observed after several hours. 3. Addition of KCN to the Na+/Ca2+-free solution caused small contractures after several hours in 7 out of 10 experiments. 4. The time to maximum Na+-free contractures was correlated to Ca2+o in a dose-dependent manner, but not influenced by catecholamine-induced myocardial damage. 5. Cell injury in the frog heart after in vivo injections of catecholamines does not affect the sarcolemmal Na+/Ca2+-exchange and is not associated with passive leakage of Ca2+ from the extracellular to the intracellular space. PMID- 2894278 TI - Single doses of catecholamines in the rat: catecholaminotropic, but not hyperglycemic. AB - 1. As in two "lower" vertebrates, the lamprey and the eel, single intravascular injections of physiological doses (2.5 micrograms/kg) of epinephrine (E) into the rat immediately increased levels of plasma dopamine (DA) and norepinephrine (NE). 2. Single doses of DA (5 micrograms/kg) enhanced circulating NE and E, while NE (5 micrograms/kg) had no clear impact on the plasma levels of the other two catecholamines (CAs). 3. These data are at variance with findings in the eel, where all three CAs are mutually stimulatory; and in the lamprey, where only E stimulates release of the other two CAs. 4. It appears that E-stimulated CA release is widespread or ubiquitous among vertebrates, and that complex interactions between circulating CAs must be considered under experimental, physiological, and clinical conditions. 5. None of the injections had a significant hyperglycemic effect. PMID- 2894279 TI - The distribution of cholinergic enzymes and 3H-QNB binding in smooth muscles of the cow stomach (Bos taurus). AB - 1. The activity of choline acetyltransferase (CAT) and cholinesterases (ChEs), and the binding of 3H-quinuclidinyl benzilate (3H-QNB) were measured in the longitudinal and circular muscle layers from the four compartments of the cow stomach. 2. CAT and ChEs activity were unevenly distributed in the various regions but distributional pattern of activity of both enzymes was very similar. 3. The maximum binding sites of 3H-QNB were also unequal in the various regions and the distribution of 3H-QNB binding was also similar to that of the activity of two enzymes. 4. These results suggest that cholinergic fibers and muscarinic receptors are not distributed symmetrically throughout the smooth muscle layers of the four compartments of the cow stomach. There may be a positive correlation between the innervation and the density of the receptors on the smooth muscle. PMID- 2894280 TI - Responses of trout fry (Salmo gairdneri) and Xenopus laevis tadpoles to cadmium and zinc. AB - 1. Toxicity of cadmium chloride and zinc sulphate in solution has been determined for Xenopus tadpoles and rainbow trout fry in recirculated water systems. 2. Both animals show approximately equal tolerance of zinc but Xenopus tadpoles tolerate cadmium at approximately 10 times the lethal concentration for trout fry. 3. In the case of Xenopus tadpoles, pre-treatment with sub-lethal concentrations of cadmium or zinc protects against subsequent exposure to either metal. For trout fry, cadmium gives little protection against later exposure to either cadmium or zinc, while zinc gives moderate protection against either metal. 4. Protection is attributed to metallothionein [MT] synthesis. PMID- 2894281 TI - New control chart for multivariate data with missing values. AB - A new multivariate statistical quality control method has been developed. It is an extension of the method developed by Kume, which is able to find abnormal values in multivariate biochemical data of a clinical laboratory. The present method makes use of the difference between two sets of data measured from the samples of the same patient obtained on different days. The Mahalanobis' distance between two samples can be calculated from the difference of their observations. If the Mahalanobis' distance of the two data is larger than the critical value decided in advance, the reliability of the measurement is doubtful. The characteristic of the present method is that it can apply to data with missing values by estimating them from measured data. Some numerical examples are shown to demonstrate the availability of the method. PMID- 2894282 TI - The Beta Blocker Heart Attack Trial: recruitment experience. AB - The Beta Blocker Heart Attack Trial (BHAT) recruited 3837 patients who within the previous 5-21-day period had experienced a myocardial infarction. The purpose of the trial was to test the efficacy of propranolol in decreasing total mortality after such an event. Recruitment was carried out over a 28-month period and involved 31 clinics, 134 hospitals, and 136 acute coronary care units. Of the 157,771 patients admitted to these units, 16,358 met the BHAT criteria for a myocardial infarction, and 23% of those eligible were ultimately randomized. The use of a coronary care unit log was helpful for tracking patients to maximize recruitment and to provide information in regard to the universe from which patients were recruited. PMID- 2894284 TI - WHO Symposium on Drug Dependence: Benefit-risk ratio assessment of agonist antagonist analgesics. August 1986. Satellite meeting to the III World Conference on Clinical Pharmacology and Therapeutics. PMID- 2894283 TI - Role of inflammatory mediators in colonic smooth muscle function in ulcerative colitis. AB - Patients with ulcerative colitis have a decrease in colonic motility which may increase their diarrheal symptoms. Studies in patients with ulcerative colitis showed that the postprandial spike response was slightly decreased and the intraluminal pressure response was absent. In vitro studies showed that the circular smooth muscle, obtained from patients with ulcerative colitis or from a rabbit model of experimental colitis, generated decreased force compared to muscle not associated with mucosal inflammation. The decrease in muscle contraction was observed with bethanechol stimulation or electrical field stimulation. Since the response to an increased extracellular concentration of potassium [( K+]0) was also diminished, the decreased response appears to be caused by an abnormality in the intrinsic contractile mechanism of colonic smooth muscle. Further studies are necessary to determine if metabolic abnormalities are present in the colonic muscle in patients with colitis. PMID- 2894285 TI - Pharmacological characteristics of agonist-antagonist analgesics. AB - A brief history and pharmacological characteristics of agonist-antagonist analgesics are presented. The importance of this class of compounds on the development of opioid-receptor concepts is described. PMID- 2894286 TI - Dependence characteristics and risk assessment of agonist-antagonist analgesics. AB - Risk assessment of dependence-producing drugs comprises assessment of two major risks: the risk that a drug is likely to be abused (abuse liability) and the harm that is likely to occur as a consequence of abuse (termed here as harm liability). Important determinants of these risks are the dependence-related pharmacological and toxicological properties of a drug. In this paper, the relationships of the drug properties to the abuse and harm liabilities are described. Next, a scoring system to assess the abuse and harm liabilities is introduced. Finally, an attempt to actually apply this system to several prototypic drugs of abuse and some agonist-antagonist analgesics is explained. PMID- 2894287 TI - The clinical usefulness of agonist-antagonist analgesics in acute pain. AB - The opioid agonist-antagonists are a heterogeneous group of compounds capable of providing analgesia sufficient to treat moderate to severe acute pain. Pentazocine, butorphanol and nalbuphine produce subjective effects which are quite different from those of morphine. Lack of mood elevation and occasional dysphoria may contribute to a lower level of patient acceptance, but all of these analgesics are significantly safer than the pure agonists. Doses in the therapeutic range are unlikely to produce dangerous levels of respiratory depression in most patients. Other opioid side-effects such as nausea, constipation and biliary spasm appear to be less frequent as well. The mu partial agonist buprenorphine shares many of the safety advantages of the older drugs, and its subjective effects appear more morphine-like. It is not clear whether mu partial agonists have real clinical advantages over kappa-type analgesics. All of these drugs are opioid antagonists and are able to precipitate abstinence in individuals with significant prior exposure to opiates. Neither absolute potency nor the ratio of agonist to antagonist effect are predictors of therapeutic usefulness. There is now an enormous amount of clinical experience with the agonist-antagonists. In many, but not all, clinical situations they are acceptable alternatives to the morphine-like drugs. PMID- 2894289 TI - Clinical observations of agonist-antagonist analgesic dependence. AB - The agonist-antagonist opioids are clinically effective analgesics with generally low abuse potential. Four agonist-antagonists are currently available for use as analgesics. Pentazocine, butorphanol and nalbuphine produce morphine-like effects in low doses and, to varying degrees, dysphoric effects as the dose is increased. Buprenorphine, an antagonist opioid of slow onset but long duration of action, produces morphine agonist effects at lower doses, and as the dose is increased, antagonist effects with minimal or no dysphoria. Clinical experience with pentazocine indicates that abuse is possible and consists of two main types: misuse (and abuse) of the drug alone by patients during treatment for pain and, abuse of the drug, often taken together with other psychoactive agents, as a substitute for the preferred drug of abuse. Few reports of abuse have appeared for butorphanol, nalbuphine and buprenorphine; however, considerable care is recommended in their use in patients, especially where there is the possibility for abuse as might occur in patients who require long-term treatment, with a history of drug abuse, and where the drug is easily obtained. PMID- 2894288 TI - The clinical usefulness of agonist-antagonistic opioid analgesics in chronic pain. AB - The mixed agonist-antagonist analgesics do not have a major role in the treatment of chronic pain. Pentazocine, the first and most widely used of this group of drugs has two major limitations: by mouth it is not a strong analgesic, but is closer in efficacy to the peripherally acting drugs aspirin and paracetamol than the weak opioids; and its use is associated with psychotomimetic side effects in 10-20 percent of patients. The weak opioid analgesics codeine and dextropropoxyphene are more effective and better tolerated than pentazocine. Buprenorphine is the most useful of the agonist-antagonists in chronic pain patients. It is potent, long-acting (6-9 h) and effective when given sublingually. However, it has a limited effective dose range and produces the same side effects as morphine-like drugs, possibly more frequently at equianalgesic doses. It may be used in the treatment of cancer pain, or in patients with chronic arthritides or other forms of chronic non-cancer pain who require a potent conventional analgesic, as an alternative to the weak opioids or to morphine in low doses. Nalbuphine and butorphanol are only available for parenteral administration which means that their usefulness in the treatment of chronic pain is limited. Meptazinol is restricted by its manufacturers to 'short term' treatment and there is little information on its use in chronic pain patients. PMID- 2894290 TI - Epidemiological survey of the use and abuse of agonist-antagonist analgesics in the Western Pacific region. AB - Epidemiological studies are carried out by the National Drug Research Centre, Malaysia on various aspects of drug use and abuse. One of the groups of substances studied are the opioid agonist-antagonists. The study utilised information submitted to international agencies and obtained through a questionnaire survey. The results showed that out of 28 countries studied, 18 reported existence of illicit traffic in these substances and of this, 17 indicated seizures. A majority of countries were unable to give consumption data and the limited information available did not allow any significant conclusions. The study did not demonstrate a significant problem of abuse globally. PMID- 2894291 TI - Benefit-risk ratio of agonist-antagonist analgesics. AB - Many agonist-antagonist analgesic substitutes for morphine have been synthesized and their safety and efficacy evaluated in animals, humans or both. Several drugs in this class have achieved regulatory approval and have reached the marketplace. Agonist-antagonist analgesics have proved clinically acceptable and are in some respects superior to the standard narcotic analgesics, most markedly in their diminished addiction liability. In other respects, however, agonist-antagonist analgesics are inferior to morphine; they probably have lower analgesic ceiling efficacy, are more likely to produce psychotomimetic effects, and can precipitate abstinence in patients physically dependent on opioids. PMID- 2894292 TI - Bevantolol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in hypertension and angina pectoris. AB - Bevantolol is a new beta-adrenoceptor antagonist which possesses a relatively high degree of selectivity for beta 1-adrenoceptors. It is devoid of intrinsic sympathomimetic activity and possesses only weak local anaesthetic properties. Interestingly, bevantolol has been shown to cause a lowering effect on peripheral vascular resistance. Available clinical data indicate that bevantolol, given once or twice daily, is an effective agent in the management of mild to moderate hypertension and stable angina pectoris. In hypertension bevantolol has been shown to be of comparable therapeutic efficacy to both atenolol and propranolol, while in patients with angina pectoris the drug compared favourably with atenolol. During short and long term administration bevantolol has been well tolerated and few patients have withdrawn from treatment because of adverse effects. However, although the properties of bevantolol may offer theoretical advantages in some patients, only a few comparative studies have been reported, and thus it is presently unclear what advantages bevantolol may offer over existing treatments for hypertension or angina pectoris. PMID- 2894294 TI - Changes in the levels of growth hormone, insulin, somatomedin C and thyroxine in sheep during immunization against somatostatin. AB - The time-related changes in the plasma levels of growth hormone, insulin, somatomedin C and thyroxine following immunization against somatostatin, have been examined in sheep. In both the treated and control lambs there was a significant increase (P less than 0.01) in growth hormone levels with time from the start of the study (at three weeks of age) through until 13 weeks of age. This increase was mirrored by increasing somatomedin C (IGF-1) levels (P less than 0.001). Thyroxine levels did not change during the period of the study. Immunization against somatostatin did not produce any significant difference between treatment groups or between sexes in the levels of growth hormone or thyroxine. However, IGF-1 level were significantly increased (P less than 0.01) by the treatment in both sexes. The changes in the levels of insulin were complicated by a marked difference between the control groups; the control females being significantly different (P less than 0.001) from all the other animals. PMID- 2894293 TI - Quazepam. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in insomnia. AB - Quazepam is a trifluoroethyl benzodiazepine hypnotic with a half-life of 27 to 41 hours, which has been shown to induce and maintain sleep in the short to long term (up to 4 weeks) treatment of patients with chronic or transient insomnia. Although its hypnotic efficacy has been well characterised against placebo, there are few clinical studies in comparison with established hypnotics, particularly over long term administration. However, preliminary evidence suggests that quazepam 15 to 30 mg is as effective as flurazepam and triazolam in usual therapeutic doses, and causes minimal rebound insomnia following its withdrawal, unlike rapidly eliminated benzodiazepines such as triazolam. The lack of rebound phenomena is likely to be attributable to the 'carryover' effects occurring after discontinuation of quazepam, which has pharmacologically active metabolites with half-lives of elimination similar to or longer than that of the parent drug. Probably because of the long half-lives of quazepam's metabolites, daytime sedation, fatigue and lethargy are the most frequently reported side effects. These side effects are most intense with the 30 mg dose and least with the 7.5mg dose, which has not been studied extensively. Hence, quazepam is an effective hypnotic which may be particularly suitable for short or medium term use in patients in whom withdrawal effects or rebound insomnia may be especially bothersome. Further definition of certain characteristics of its profile--such as its long term use and potential for development of tolerance or dependence, effects on psychomotor skills, efficacy of the 7.5mg dose, and suitability in elderly patients and patients with chronic organic diseases--will assist in more clearly defining its ultimate place in therapy. PMID- 2894296 TI - Dynorphin A inhibits and naloxone increases the electrically stimulated release of oxytocin but not vasopressin from the terminals of the neural lobe. AB - Oxytocin release from the rat neurohypophysis is under endogenous opioid inhibition. It has recently been established that dynorphin precursor-derived peptides are colocalized with vasopressin (VP) in the secretory granules in nerve terminals of the neural lobe, and that the opiate receptors in the neural lobe are restricted to the kappa-subtype. Therefore, we hypothesized that dynorphin, which is copackaged and thus coreleased with VP, is the endogenous opioid that inhibits release from neighboring oxytocin (OT) terminals. To test this hypothesis we examined the effects of dynorphin-(1-8), dynorphin-(1-17), and naloxone on the electrically stimulated release of OT and VP from isolated rat neurointermediate lobes throughout a range of stimulus frequencies. Both dynorphin-(1-8) and -(1-17) (2 microM) produced a substantial reduction in OT release during a 4-Hz stimulus, and this effect was abolished by naloxone (10 microM). Neither form of dynorphin, however, affected OT secretion at a stimulus frequency of 12 or 30 Hz at concentrations up to 10 microM. Naloxone (10 microM) by itself did not affect OT release during the 4-Hz stimulus, but it produced a substantial increase in OT release at a stimulus frequency of 12 Hz. In contrast, neither form of dynorphin produced inhibition, nor did naloxone augment VP secretion at any frequency tested. Frequency-dependent secretion curves (4, 8, 12, 20, and 30 Hz) for OT and VP in the presence and absence of naloxone indicated that the degree of naloxone augmentation of OT release at a given stimulus frequency was positively correlated with the amount of VP release at that frequency. These data support the hypothesis that dynorphin released in parallel with VP during in vitro stimulations of the rat neurohypophysis simultaneously inhibits stimulated OT release. PMID- 2894295 TI - Antagonistic effects of growth hormone-releasing factor and somatostatin on brain histamine. AB - Studies on the morphological distribution of histamine (HA)-secreting neurons and their hypothalamic projections suggest that HA may play a key role in regulating neuroendocrine functions, some of which have been recently elucidated. To investigate possible interactions between the somatotropinergic and histaminergic systems in the brain, the effects of GRF-44 [0.1-10 micrograms intracerebroventricular (icv)] and somatostatin (SS-14; 0.1-10 micrograms, icv) on HA in five different parts of the hypothalamo-hypophyseal system, and in the hippocampus and frontal cortex, were studied using a highly sensitive HPLC system for determination of HA. GRF-44 (1 microgram, icv) elicited significant (P less than 0.005) increases in the concentration of HA in the anterior hypothalamus, posterior hypothalamus, median eminence, adenohypophysis, neurohypophysis, frontal cortex, and, to a lesser extent, in the hippocampus, after a clear time dependent pattern with maxima 15 min after injection. In contrast, SS-14 (1 microgram, icv) significantly (P less than 0.005) decreased the levels of HA in all areas studied, except in the neurohypophysis. The SS-induced HA levels reached minima 30 min after injection. The antagonistic effects of GRF-44 and SS 14 on the release of brain HA were dose dependent, showing an inverse linear correlation within the range 0.1-10 micrograms in the anterior hypothalamus (r = 0.59) and posterior hypothalamus (r = -0.75). Responses of HA to GRF-44 and SS-14 (range: 0.1-10 micrograms) also exhibited an inverse linear correlation in the median eminence (r = -0.90) and adenohypophysis (r = -0.58), while in the hippocampus and frontal cortex the antagonistic effects of GRF and SS displayed an inverse curvilinear correlation. SS-14 ED50 values ranged from 0.6 to 1.75 nmol with Emax of 0.65-6.10 nmol. GRF-44 ED50 values ranged from 0.02-0.3 nmol and the Emax values oscillated between 0.2 and 1.90 nmol in the regions studied. The greatest responses of HA to GRF-44 and SS-14 were obtained in the hypothalamo hypophyseal system. Although brain HA is present in both the neuronal and the mast cell compartments, changes induced in the concentration of HA by centrally administered GRF-44 and SS-14 appear to occur mostly in the neuronal compartment. Therefore, it is likely that the somatotropinergic and histaminergic systems reciprocally interact at the central level to regulate still unknown neuroendocrine functions. PMID- 2894297 TI - Alpha 1-adrenergic stimulation of in vitro growth hormone release and cytosolic free Ca2+ in rat somatotrophs. AB - The effects of alpha 1-adrenergic agents on GH release and intracellular free Ca2+ concentration ([Ca2+]i) were investigated in purified rat somatotroph preparations. Phenylephrine (PHE) stimulated in vitro GH release; the maximal effect (2.5-fold stimulation) occurred at 1 microM PHE. The effect was completely blocked by the alpha-adrenergic antagonist phentolamine and partially counteracted by the beta-antagonist propranolol. Experiments with the fluorescent Ca2+ probe fura 2 show that PHE causes [Ca2+]i to rise from 178 +/- 31 nM (mean +/- SE; n = 25) to 370 +/- 55 nM (n = 9). This effect was complete within 20 sec and was maintained for at least 5-10 min. The rise was rapidly interrupted by administration of 1 microM phentolamine. The beta-receptor agonist isoproterenol caused a small [Ca2+]i rise due to action on alpha 1-adrenoreceptors. The PHE induced [Ca2+]i rise showed two components: an initial peak due to Ca2+ mobilization from intracellular stores and a subsequent rise due to Ca2+ influx from the extracellular space. Somatostatin (SRIF) lowered both resting [Ca2+]i and Ca2+ influx stimulated by PHE. Pertussis toxin pretreatment did not modify PHE-induced [Ca2+]i changes, while it completely prevented the effect of SRIF on both resting and triggered [Ca2+]i, thus suggesting that a GTP-binding protein sensitive to the toxin is involved in the transduction of SRIF action. The increase in cAMP induced by cholera toxin pretreatment modified neither PHE nor SRIF action on [Ca2+]i. In conclusion, in rat somatotrophs Ca2+ mobilization and influx are stimulated by alpha 1-adrenergic agents, and this triggered [Ca2+]i rise results in a stimulation of GH release. In these cells SRIF is able to reduce both resting [Ca2+]i levels and [Ca2+]i increases induced by alpha 1 adrenergic activation. PMID- 2894299 TI - Causes and types of traumatic tooth injuries treated in a public dental health clinic. PMID- 2894298 TI - Atrial natriuretic peptide, oxytocin, and vasopressin increase guanosine 3',5' monophosphate in LLC-PK1 kidney epithelial cells. AB - The effect of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), and oxytocin (OT) on cAMP and cGMP accumulation was investigated in LLC-PK1 kidney epithelial cells. The addition of ANP, AVP, and OT to intact cells produced a time- and concentration-dependent increase in cGMP accumulation. ANP produced a 1.7-fold increase in cGMP at 10 pM and a maximal 28-fold increase in cGMP at 1 microM. ANP had no effect on basal or AVP-induced stimulation of cAMP accumulation. OT was 10-fold more potent than AVP at increasing cGMP levels, producing a 2.1-fold increase in cGMP at 0.1 nM, whereas AVP was 100-fold more potent at increasing cAMP levels. At a concentration of 1 microM, AVP and OT produced a maximal 12 to 14-fold increase in cGMP, while OT and AVP produced 50- and 90-fold increase in cAMP, respectively. The selective OT agonist [Thr4, Gly7]oxytocin was very effective at increasing cGMP, but not at increasing cAMP levels. The V2-vasopressin agonist [deamino-Pen1,Val4, D-Arg8]vasopressin did not increase cGMP levels, but produced a 20-fold increase in cAMP levels. The addition of ANP together with either AVP or OT produced an additive increase in cGMP content. Simultaneous addition of AVP and OT did not lead to a greater increase in cAMP or cGMP levels. These results suggest that the AVP- and OT induced increase in cGMP is mediated by OT receptors, whereas the increase in cAMP is probably mediated by vasopressin receptors. ANP increased the activity of particulate guanylate cyclase by 6-fold, while AVP and OT has no effect on particulate guanylate cyclase activity. The relatively selective inhibitor of soluble guanylate cyclase, methylene blue, had no effect on the ANP-induced increase in cGMP content in intact cells, but produced a 50% inhibition of the increase in cGMP by AVP and OT. Methylene blue did not alter the stimulation of cAMP by AVP or OT. These results demonstrate that ANP, AVP, and OT increase cGMP in LLC-PK1 kidney epithelial cells. The increase in cGMP by ANP is mediated by particulate guanylate cyclase, whereas AVP and OT probably increase cGMP by interacting with OT receptors coupled to soluble guanylate cyclase. PMID- 2894300 TI - Experimental dental traumatology: development of a model for external root resorption. PMID- 2894301 TI - The importance of follow-up exams after tooth trauma. PMID- 2894302 TI - Molecular basis of phenylketonuria and recombinant DNA strategies for its therapy. AB - Mutations in the human phenylalanine hydroxylase gene associated with two prevalent mutant alleles have been identified and shown to be in linkage disequilibrium with the corresponding mutant restriction fragment length polymorphism haplotypes. These results suggest the possibility of carrier detection in the population without a prior family history of phenylketonuria (PKU). Furthermore, recombinant retroviruses containing the full-length human phenylalanine hydroxylase cDNA have been constructed and used to transduce functional enzymatic activity into cultured hepatoma cells. Together with the recent success in retroviral infection of primary mouse hepatocytes, it will be possible to use the mouse model to investigate somatic gene therapy for PKU. PMID- 2894303 TI - Molecular aspects of urea cycle enzymes and related disorders. AB - Amino acid sequence of rat ornithine transcarbamylase (OTC) precursor containing an NH2-terminal presequence of 32 residues was deduced from the cDNA sequence. Comparison with the human and Escherichia coli enzymes indicated that regions containing the putative binding sites for the substrates are highly conserved among the three species. cDNA clones for rat and human liver arginase were isolated and predicted amino acid sequences were compared with that of the yeast enzyme. There are several regions highly conserved among the three species which may be important for catalysis. Several cases of carbamyl phosphate synthetase I and OTC deficiencies were analyzed for enzyme activity, enzyme amount and mRNA activity. PMID- 2894304 TI - Pathochemistry, pathogenesis and enzyme replacement in multiple-sulfatase deficiency. AB - Multiple-sulfatase deficiency (MSD) is now considered to be heterogeneous and could be classified into three or four clinical phenotypes according to the onset of the disease: neonatal, late infantile, juvenile and possibly adult type. Neonatal-type MSD shows severe clinical involvement and practically no arylsulfatase A, B and C activities in cultured skin fibroblasts. Furthermore, arylsulfatase A activity in neonatal-type MSD was not enhanced by the addition of thiosulfate. Therefore, it is distinct from late infantile-type MSD. The degradation of 14C-sulfatide can occur in MSD-cultured skin fibroblasts and was much higher than in late infantile-type MLD. The addition of thiol protease such as leupeptin to cultured MSD skin fibroblasts enhanced arylsulfatase A activity as well as the degradation of 14C-sulfatide. This suggests that the decreased activities of arylsulfatase A is due to an acceleration of the enzyme degradation. Enzyme replacement by the addition of arylsulfatases of different sources (human liver, brain, fungus) was carried out in cultured MSD skin fibroblasts. Human enzymes of arylsulfatase A and B were mostly taken up by MSD cells rather than those of fungus origin. By the exposure to leukocytes to cultured skin fibroblasts, MSD cells corrected arylsulfatase A and B activities. PMID- 2894305 TI - Genetic analysis of human hypoxanthine-guanine phosphoribosyltransferase deficiency. AB - Hypoxanthine-guanine phosphoribosyltransferase (HPRT; IMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) functions in the purine-metabolic salvage pathway. Two clinical syndromes are associated with a deficiency in HPRT enzyme activity. Virtually complete deficiency leads to the Lesch-Nyhan syndrome, whereas partial deficiency results in hyperuricemia and severe gouty arthritis. Marked heterogeneity in the mutations leading to HPRT deficiency has been found. Mutant enzymes vary with respect to levels of HPRT immunoreactive protein, electrophoretic migration, kinetic properties and amino acid sequence. Analysis of DNA and RNA from patients with HPRT deficiency has revealed point mutations, an internal gene duplication and partial as well as complete gene deletions accounting for the various HPRT mutant enzymes. PMID- 2894306 TI - Molecular biology of the alpha-L-fucosidase gene and fucosidosis. AB - Human alpha-L-fucosidase, a lysosomal enzyme, hydrolyzes alpha-L-fucose from glycolipids and glycoproteins. Its activity is deficient in human fucosidosis an autosomal recessive disease. In order to understand the molecular basis of this lysosomal storage disorder we have cloned several cDNAs coding for human alpha-L fucosidase from a human hepatoma and a human liver cDNA library constructed in lambda gt11. Compiling the cDNA sequences of these clones we have identified 1,829 base pairs (bp) encoding human alpha-L-fucosidase. This includes an open reading frame of 1,172 bp, a consensus polyadenylation signal AAT AAA and a poly(A)+ tail. The sequence is incomplete at the 5'-end, and clones encoding the amino terminus of the native protein, the propeptide and leader signal have not yet been isolated. The open reading frame encodes for 390 amino acids with a calculated Mr of 45,557. This represents 78-95% of the mature processed alpha-L fucosidase. The availability of these cDNA clones has enabled us to map the structural gene for alpha-L-fucosidase to chromosome 1p34.1-1p36.1 by Southern blot analysis of DNA from human-rodent somatic cell hybrids and by in situ hybridization. Furthermore, a Pvu II restriction fragment length polymorphism (RFLP) has been identified at the human alpha-L-fucosidase gene locus. Analysis of mRNA by Northern blotting gives a major species of 2.25 kb. In 4 patients with fucosidosis no mRNA signal was detected and Western blots gave no immunoreactive enzyme. Southern blotting after Eco RI digestion in two fucosidosis families revealed a banding abnormality (extra 6-kb band).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894307 TI - Hyperketotic states due to inherited defects of ketolysis. AB - From the description of 2 unrelated patients with succinyl-CoA transferase (3 OAT) deficiency and 1 patient with acetoacetyl-CoA thiolase (AAT) deficiency, we have attempted to draw the clinical and metabolic consequences of such defects. The association of recurrent attacks of severe ketoacidosis with blood glucose levels generally high or normal, low lactacidemia and low ammonemia is the most common presentation of these disorders. In 3-OAT deficiency, a potentially fatal disorder, there is a permanent ketosis with the only excretion of 3 hydroxybutyrate, acetoacetate and 3-hydroxyisovalerate. AAT patients usually excrete, in addition to the usual ketone bodies, 2-methyl-3-hydroxybutyrate and tiglylglycine; 2-methyl-acetoacetate may also be present. Both conditions can be identified by enzymatic analysis in cultured fibroblast. These disorders can mimic diabetic ketoacidosis or salicylism and can easily be missed. The knowledge of these ketolytic defects must severely question the complacent diagnosis of 'fasting ketoacidosis' or 'idiopathic ketotic hypoglycemia', mainly when severe metabolic acidosis is present. PMID- 2894308 TI - Experience with alfentanil infusion as an intensive care sedative analgesic. AB - A sedative regimen for use in intensive care based on an i.v. infusion of alfentanil has been evaluated in 32 patients. The mean duration of stay was 7.7 days and the total dose of alfentanil given ranged from 7 to 2308 mg. Most patients required 2-3 mg h-1 of alfentanil supplemented with an hypnotic to provide sleep. The technique was judged successful and was well tolerated by patients. No significant side-effects were observed and the wakefulness of the patients was a prominent feature. Weaning from mechanical ventilation was performed while maintaining the infusion in a number of patients, and in these there was no prolonged respiratory depression. PMID- 2894309 TI - Enzymatic properties of single-chain and two-chain forms of a Lys158----Glu158 mutant of urokinase-type plasminogen activator. AB - Recombinant single-chain urokinase-type plasminogen activator (rscu-PA), in which the plasmin-sensitive peptide bond Lys158-Ile159 is destroyed by site-specific mutagenesis of Lys158 to Glu (rscu-PA-Glu158), is quantitatively converted to two chain urokinase-type plasminogen activator (rtcu-PA-Glu158) by treatment with endoproteinase Glu-C (Staphylococcus aureus V8 proteinase). The catalytic efficiency (k2/Km) of rscu-PA-Glu158 for the activation of plasminogen is 20 times lower (0.0001 microM-1 s-1) than that of rscu-PA (0.002 microM-1 s-1). In contrast, rtcu-PA-Glu158 has very similar properties to rtcu-PA obtained by digestion of rscu-PA with plasmin, including binding to benzamidine-Sepharose, catalytic efficiency for the activation of plasminogen (0.035 microM-1 s-1 versus 0.046 microM-1 s-1) and fibrinolytic activity in an in vitro plasma clot lysis system. It is concluded that the amino acid in position 158 is a main determinant of the functional properties of single-chain urokinase-type plasminogen activator but not of the two-chain form. PMID- 2894310 TI - Purified subunit delta of chloroplast coupling factor CF1 reconstitutes photophosphorylation in partially CF1-depleted membranes. AB - The ATP synthase of chloroplasts consists of the proton channel, CF0, and the catalytic part, CF1, which carries nucleotide-binding sites on subunits alpha and beta. The still poorly understood interaction between CF0 and the catalytic sites on CF1 is mediated by the smaller subunits gamma, delta and epsilon of CF1. We investigated the ability of purified delta to block proton leakage through CF0 channels after their exposure by removal of the CF1 counterpart. Thylakoids were partially depleted of CF1 by EDTA treatment. This increased their proton permeability and thereby reduced the rate of photophosphorylation. Subunit delta was isolated and purified by FPLC [Engelbrecht, S. and Junge, W. (1987) FEBS Lett. 219, 321-325]. Addition of delta to EDTA-treated thylakoids reconstituted high rates of phenazine-methosulfate-mediated photophosphorylation. Since delta does not interact with nucleotides by itself, the reconstitution was due to a reduction of the proton leakage through open CF0 channels. The molar ratio of purified delta over exposed CF0, which started to elicit this effect, was 3:1. However, if delta was added together with purified CF1 lacking delta, in a 1:1 molar ratio, the relative amount over exposed CF0 was as low as 0.06. This corroborated our previous conclusion [Lill, H., Engelbrecht, S., Schonknecht, G. and Junge, W. (1986) Eur. J. Biochem. 160, 627-634] that only a very small fraction of exposed CF0 was actually proton-conducting but with a very high unit conductance. CF1 including delta was apparently rebound preferentially to open CF0 channels. Although the ability of delta to control proton conduction through CF0 was evident, it remains to be established whether delta acts as a gated proton valve or as a conformational transducer in the integral CF0CF1 ATPase. PMID- 2894311 TI - Gi affects the agonist-binding properties of beta-adrenoceptors in the presence of Gs. AB - Pertussis-toxin-catalyzed ADP-ribosylation of Gi in S49 membranes, but not in S49AC- membranes, which lack Gs, induces a threefold reduction of isoproterenol affinity to the beta-adrenoceptors. A similar treatment of turkey erythrocyte membranes, which are devoid of functional Gi, has no effect on beta-agonist affinity to their beta-adrenoceptors. Non-hydrolyzable analogs such as GTP[S] induce a larger decrease in beta-adrenoceptor affinity in S49 cells towards the agonist isoproterenol as compared to pertussis-toxin-catalyzed ADP-ribosylation of Gi. These results suggest that Gi affects beta-adrenoceptor affinity to its agonist and that this interaction requires the presence of Gs. It seems, therefore, that Gi physically interacts with Gs to exert its effects on the receptor and probably on adenylate cyclase as well. Our ability to detect (a) the effect of pertussis-toxin-catalyzed ADP-ribosylation in S49 cells on beta-agonist affinity and (b) the quantitative difference between the effect of pertussis toxin (approx. threefold) and GTP[S] (fivefold to sevenfold) depends on the use of a simple but rigorous method to study in detail the affinity of beta-agonists to their receptors. This method seems to be superior to the analysis of displacement curves as a means to examine receptor-ligand interactions. PMID- 2894312 TI - The Beta-Blocker Pooling Project (BBPP): subgroup findings from randomized trials in post infarction patients. The Beta-Blocker Pooling Project Research Group. AB - The objective of the Beta-Blocker Pooling Project (BBPP) was to collect and analyse data from the major long-term secondary prevention trials in order to determine whether there are subsets of post-infarction patients who benefit to a greater or lesser extent from beta-blocker therapy than the average patient population. One-year all-cause mortality data from nine trials involving 13,679 patients were obtained. Overall, mortality was 24% lower in the beta-blocker group compared to the placebo group. However, there was heterogeneity among the results of the trials, which tested seven different beta-blockers. Subgroups with high placebo group mortality (e.g. patients with a history of previous myocardial infarction (MI), angina pectoris, mechanical or electrical complications, and digitalis usage) seemed to benefit particularly from beta-blocker treatment. These findings were consistent in the nine trials. Patients in the lower risk subgroups also appeared to benefit from beta-blockers, but this benefit was smaller in absolute terms and inconsistent across the trials. There was no evidence that treatment outcome was related to gender, baseline level of heart rate or blood pressure, or time of initiation of treatment after hospital admission. In conclusion, the Pooling Project indicates that high risk MI patients, without contraindications to beta-blockers, are the prime candidates for long-term therapy, but the lower risk patients may also receive some benefit. PMID- 2894313 TI - Mechanism of the inhibitory action of cyclooxygenase inhibitors on leukocyte infiltration: involvement of endogenous histamine. AB - The mechanism of the inhibitory action of cyclooxygenase inhibitors on leukocyte accumulation in the inflammatory locus was investigated in an allergic inflammation of the air pouch types in rats. Three kinds of cyclooxygenase inhibitors, indomethacin, diclofenac and tiaprofenic acid, caused not only inhibition of the vascular permeability response and leukocyte accumulation but also elevation of histamine levels in the exudate. These effects of indomethacin were all reversed by local administration of prostaglandin E2. Pyrilamine, an H1 antagonist, did not affect the anti-inflammatory actions of indomethacin. The H2 antagonists, cimetidine, ranitidine and famotidine, decreased the inhibitory effect of indomethacin on leukocyte accumulation without affecting the inhibitory action on vascular permeability. These results indicate that the inhibitory action of cyclooxygenase inhibitors on leukocyte accumulation is derived from their blocking effect against generation of PGE2 which works as an inhibitory factor on the production of histamine in the inflammatory tissues. PMID- 2894314 TI - Excessive grooming induced by somatostatin or its analog SMS 201-995. AB - Intracerebroventricular (i.c.v.) administration of somatostatin or SMS 201-995 induces excessive grooming behavior in rats. The grooming inducing effect of somatostatin is rather weak, as doses of 300 ng or less did not result in increased total grooming scores. In contrast a dose of 10 ng SMS 201-995 already significantly increased the total grooming scores. However, doses of 100 ng and more did not further increase the total grooming scores reached with a 50 ng dose of this peptide. Systemic administration of SMS 201-995 in doses up to 900 micrograms did not result in excessive grooming behavior. The patterns of excessive grooming induced by i.c.v. SMS 201-995 and somatostatin were characterized by a predominant display of scratching. Since peptide-induced scratching is mainly due to activation of opiate receptor systems it is suggested that opiate receptors are involved in the behavioral response to SMS 201-995 and somatostatin administration. This suggestion is further supported by the suppressive effect of naloxone on excessive grooming induced by these peptides. Haloperidol and neurotensin also suppress the excessive grooming induced by somatostatin but not that induced by SMS 201-995. Finally, tolerance developed to the grooming-inducing effect of SMS 201-995 and somatostatin. In addition there was cross tolerance between somatostatin and SMS 201-995. PMID- 2894315 TI - Modulation by noradrenaline and yohimbine of noradrenergic transmission in the guinea-pig mesenteric artery. AB - In the guinea-pig mesenteric artery, transmitter release modulated by noradrenaline (NA) or yohimbine was estimated from changes in amplitude of the excitatory junction potential (e.j.p.) recorded from smooth muscle cells. NA decreased the amplitude of the e.j.p. with no change in the facilitation. Yohimbine antagonized the effect of NA on the e.j.p. amplitude and enhanced the facilitation of e.j.p.; the latter action was not antagonized by NA. TTX resistant e.j.p.s evoked by stronger intensity of stimuli were not affected by NA or yohimbine. It is concluded that NA inhibits and yohimbine enhances the release of transmitter, and that the latter event involves prejunctional alpha adrenoceptor-dependent and -independent processes. PMID- 2894316 TI - Characterization of alpha-adrenoceptors mediating sympathetic vasoconstriction in rat autoperfused hindlimb: effects of SK&F 104078. AB - In the autoperfused hindlimb of pithed rats, vasoconstrictor responses to intra arterial infusions of the selective alpha 2-adrenoceptor agonist, B-HT 933, were antagonized by the alpha 2-adrenoceptor antagonist, rauwolscine (1 mg/kg i.v.), and by the selective postjunctional alpha 2-adrenoceptor antagonist, SK&F 104078 (1 mg/kg), but not by the selective alpha 1-adrenoceptor antagonist, prazosin (0.1 mg/kg). In contrast, responses to the selective alpha 1-adrenoceptor agonist, methoxamine, were antagonized by prazosin, but not by rauwolscine or SK&F 104078. Vasopressor responses to stimulation of sympathetic nerves were inhibited by prazosin, increased by rauwolscine, and not affected by SK&F 104078. The results indicate that vascular neuroeffector transmission in rat hindlimb is mediated by postjunctional alpha 1-adrenoceptors, and that SK&F 104078 is a selective antagonist of postjunctional alpha 2-adrenoceptor, and lacks the prejunctional alpha 2-adrenoceptor antagonist action of rauwolscine. PMID- 2894318 TI - The endocytosis of epidermal growth factor in A431 cells: a pH of microenvironment and the dynamics of receptor complex dissociation. AB - The endocytosis and intracellular fate of epidermal growth factor (EGF) were studied in A431 cells. After 15-20 min of internalization at 37 degrees C, rhodamine-labeled EGF (EGF-Rh) accumulated into large juxtanuclear compartment consisting of closely related vesicles. This structure was shown to be localized in the para-Golgi region. Fluorescein-labeled transferrin (Tr-FITC) was observed in the same region when added to the cells simultaneously with EGF-Rh. Using microscope spectrofluorometer, we determined that the Tr-FITC-containing para Golgi structures have a pH of 6.1 +/- 0.3 while lysosomes containing dextran fluorescein have a pH of 5.0 +/- 0.2. To study the dynamics of EGF-receptor dissociation during endocytosis a mild detergent treatment of living cells was used for extraction of an intracellular receptor-unbound EGF. During the first hour of internalization at 37 degrees C, neither significant dissociation of EGF receptor complexes nor EGF degradation was observed. After 3 h of endocytosis, the percentage of unbound EGF increased to 55% of the total internalized EGF. These results suggest that EGF remains associated with receptors during endocytosis in A431 cells until it is transferred to lysosomes where the pH of the EGF microenvironment is dropped to 5. A prolonged presence of EGF-receptor complexes in the para-Golgi region might be of importance in mitotic signaling. PMID- 2894317 TI - Receptor autoradiography with [3H]L-glutamate reveals the presence and axonal transport of glutamate receptors in vagal afferent neurones of the rat. PMID- 2894319 TI - Actions of excitatory amino acid antagonists on geniculo-cortical transmission in the cat's visual cortex. AB - To test the possibility that glutamate and aspartate are transmitters at geniculo cortical synapses and to elucidate which type of receptors for the excitatory amino acids (EAA) operate at these synapses, we studied effects of microiontophoretic administration of EAA antagonists on the responses of visual cortical neurons to afferent electrical and visual stimulation in the cat. The antagonists used were kynurenate, a non-selective antagonist for all classes of EAA receptors and 2-amino-5-phosphonovalerate (APV), a selective antagonist for N methyl-D-aspartate (NMDA)-preferring receptors. The administration of kynurenate suppressed responses elicited by electrical stimulation of the dorsal lateral geniculate nucleus (LGN) and optic chiasm (OX) of 65% of the cells tested. This suppression was more marked for the short-latency responses which were evoked monosynaptically from the LGN, than for the longer-latency responses. In contrast with the effectiveness of kynurenate, APV failed to suppress electrically and visually elicited responses in 66% of the cortical cells. Such differences between kynurenate and APV were particularly prominent in layers IV and VI, which receive direct inputs from the LGN, but were less marked or were not recognizable in layers II + III and V. These results support previous suggestions that EAAs may be excitatory transmitters in the cerebral cortex, at least at geniculo cortical synapses, and indicate further that EAA receptors of the "non-NMDA type" may be involved in afferent synaptic transmission in the cat's visual cortex. PMID- 2894320 TI - Supersensitivity of presynaptic receptors involved in the dopaminergic control of striatal high affinity glutamate uptake after 6-hydroxydopamine lesion of nigrostriatal dopaminergic neurons. AB - The effects on striatal high affinity glutamate uptake (HAGU) of an apomorphine injection administered either alone or along with an electrical stimulation of the frontal cortex were compared between intact control rats and animals with 6 hydroxydopamine (6-OHDA) induced lesions of the nigrostriatal dopaminergic neurons. 6-OHDA injury was previously shown to have no effect either on basal HAGU or on the HAGU increase occurring in response to cortical stimulation. Apomorphine injected 1 h before HAGU determination at a dose of 5 mg/kg did not modify basal HAGU but totally abolished HAGU responsiveness to cortical stimulation applied 30 min after the apomorphine administration in both groups of animals. However, the duration of apomorphine induced inhibition of the cortically evoked striatal HAGU response in animals with 6-OHDA injury greatly exceeded that observed in intact rats. Indeed, in intact animals, cortical stimulation again became able to increase striatal HAGU when applied more than 6 h after apomorphine injection, while in 6-OHDA injected rats, HAGU responsiveness to cortical stimulation was restored only as from 7 days after apomorphine administration. Moreover, in rats given 6-OHDA injections apomorphine efficiently inhibited the activating effect of cortical stimulation on HAGU at doses at least 20 times lower than those required to obtain the same effect in intact animals. These results suggest that in both intact and 6-OHDA injected rats, apomorphine acts by counteracting the HAGU increase occurring in response to cortical stimulation and that the sites involved in this action develop a supersensitivity response to striatal dopaminergic deafferentation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894321 TI - Human platelet 5-hydroxytryptamine receptors: binding of [3H]-lysergic acid diethylamide (LSD). Effects of chronic neuroleptic and antidepressant drug administration. AB - Chronic treatment with phenothiazines and thioxanthenes has been found to enhance 5-HT-induced aggregation of human platelets. A method has been developed to study 5-HT2 receptor binding sites on platelets utilising [3H]-LSD and more recently 125I/LSD. Results are presented which suggest that the LSD binding site is indeed the 5-HT2 binding site and that the LSD binding characterises the specific receptor responsible for 5-HT-induced shape change and aggregation. In a group of patients receiving phenothiazines or thioxanthenes, the Bmax of LSD binding was increased. The mean binding affinity was decreased possibly due to a persistence of neuroleptic in the platelet membrane preparation. Analysis showed that this was not the reason why the mean binding capacity was increased. The results show that chronic phenothiazine and thioxanthene delta treatment 'up-regulates' platelet 5-HT2 binding sites and that this may be accompanied by increased sensitivity to platelet aggregation by 5-HT. In normal subjects desipramine treatment increased the Bmax of platelet LSD binding and this was accompanied by an increased prolactin response to tryptophan which is thought to be mediated by central 5-HT function. PMID- 2894322 TI - Further analysis of cDNA clones for maize phosphoenolpyruvate carboxylase involved in C4 photosynthesis. Nucleotide sequence of entire open reading frame and evidence for polyadenylation of mRNA at multiple sites in vivo. AB - Four clones of cDNA for phosphoenolpyruvate carboxylase [EC 4.1.1.31] were obtained from a maize green leaf cDNA library by colony hybridization. The largest cDNA was of full-length (3335 nucleotides), being 243 nucleotides longer than the cDNA cloned previously [(1986) Nucleic Acids Res. 14, 1615-1628]. Alignment of the sequence for the N-terminal coding region found in two of the four clones with the sequence reported previously, established the sequence of the entire coding region for the enzyme. The sequencing of 3'-untranslated region of the clones revealed that the poly(A) tract is attached at multiple sites in vivo. PMID- 2894323 TI - Respiration driven C1- uptake by submitochondrial particles. AB - Both Mg2+ and oligomycin are required for the establishment of a membrane potential and the uptake of Cl- in submitochondrial particles prepared from rat liver. The effect of oligomycin is considered to be due to blocking of H+ conduction through exposed F0 channels of the ATPase complex whereas Mg2+ may more directly affect the anion-conducting channel. PMID- 2894324 TI - Occurrence and possible roles of acetoacetyl-CoA thiolase and 3-ketoacyl-CoA thiolase in peroxisomes of an n-alkane-grown yeast, Candida tropicalis. AB - Two kinds of 3-ketoacyl-CoA thiolases were found in the peroxisomes of Candida tropicalis cells grown on n-alkanes (C10-C13). One was a typical acetoacetyl-CoA thiolase specific only to acetoacetyl-CoA, while another was 3-ketoacyl-CoA thiolase showing high activities on the longer chain substrates. A high level of the latter thiolase activity in alkane-grown cells was similar to that of other enzymes constituting the fatty acid beta-oxidation system in yeast peroxisomes. These facts suggest that the complete degradation of fatty acids to acetyl-CoA is carried out in yeast peroxisomes by the cooperative contribution of acetoacetyl CoA thiolase and 3-ketoacyl-CoA thiolase. PMID- 2894327 TI - The tissue dependent expression of hamster P-glycoprotein genes. AB - Using a sensitive RNase protection assay, we have measured the levels of P glycoprotein mRNA in fourteen different Chinese hamster tissues and in three cell lines to determine whether a relationship exists between the level of P glycoprotein expression and the occurrence of primary and acquired multidrug resistance (MDR) in cancer. P-Glycoprotein mRNA was detected in all tissues, suggesting that the protein is a normal constituent of the cell. High levels of P glycoprotein mRNA were found in oesophagus, testis and uterus. Intermediate levels in brain, lung and ovary, and a very low level in the adrenal gland, bladder, bone marrow, heart, kidney, liver and spleen. There is no obvious correlation between this expression pattern and the occurrence of primary or acquired MDR. PMID- 2894326 TI - Inhibition of the H+-ATPase in bovine adrenal chromaffin granule ghosts by diethylstilbestrol. Evidence for a tight coupling between ATP hydrolysis and proton translocation. AB - Diethylstilbestrol (DES) was found to inhibit reversibly the hydrolysis of MgATP (80% at 100 microM) and proton pump activity (I50 approximately equal to 15 microM, complete at 100 microM) in chromaffin granule ghosts. The parallel inhibition suggests a tight kinetic coupling between the two activities. The Mg2+ ATPase activity, but not proton pumping, was partially restored by N,N' dicyclohexylcarbodiimide, indicating that the two inhibitors in combination cause a partial uncoupling. The non-competitive type of inhibition shows that the action of DES is distal to the site of ATP binding and hydrolysis. Although unspecific, the interaction of DES with the chromaffin granule membrane seems primarily to affect the H+-ATPase. PMID- 2894328 TI - Microdot ELISA: development of a sensitive and rapid test to identify the source of mosquito blood meals. PMID- 2894325 TI - The mitochondrial ATP synthase inhibitor protein binds near the C-terminus of the F1 beta-subunit. AB - The specific, mitochondrial ATP synthase protein (IF1) was covalently cross linked to its binding site on the catalytic sector of the enzyme (F1-ATPase). The cross-linked complex was selectively cleaved, leaving IF1 intact to facilitate the subsequent purification of the F1 fragment to which IF1 was cross-linked. This fragment was identified by sequence analysis as comprising residues 394-459 on the F1 beta-subunit, near the C-terminus. This finding is discussed in the light of secondary structure predictions for both IF1 and the F1 beta-subunit, and sequence homologies between mitochondrial and other ATP synthases. PMID- 2894329 TI - Studies on the role of indigenous fishes in the control of mosquito breeding. PMID- 2894330 TI - Tulobuterol: a full beta-adrenoceptor agonist or a partial beta-agonist with membrane stabilizing activity? AB - 1. The effects of tulobuterol on the atrial rate was compared with those of isoproterenol, pindolol and propranolol in spontaneously beating isolated right atria of the rat. 2. Isoproterenol markedly increased atrial rate. To the contrary, propranolol, pindolol and tulobuterol decreased atrial frequency. The chronotropic effect of tulobuterol was similar to that of pindolol but lower than that of propranolol. 3. Interactions between tulobuterol and isoproterenol showed that tulobuterol potentiated the chronotropic effect of low concentrations of isoproterenol but reduced the positive chronotropic response to higher concentrations of isoproterenol. 4. These results suggest that tulobuterol is a partial agonist on atrial beta-receptor but also seems to have another action (possibly a membrane stabilizing activity) which reduced the originally induced effect on beta-receptors as a non-competitive antagonist. PMID- 2894331 TI - Daily changes in the mouse cingulate cortex responsivity to neurotransmitters and depolarizing medium: an extracellular in vitro study. AB - 1. The reaction of the mouse cingulate cortex neurons to the applied substances, measured as changes in the spontaneous activity, was investigated for daily variations in the in vitro slice preparation. 2. Glutamate- and GABA-evoked excitation and inhibition, respectively, were followed by long-lasting after effects which showed greater potency in slices prepared in the evening. 3. Acetylcholine evoked excitation, inhibition and multiphasic effects. The incidence of an excitatory reaction prevailed in slices prepared in the evening. 4. The majority of cells studied in the evening were inhibited after application of a depolarizing medium, while in the morning the reaction was equally divided between excitation and inhibition. 5. The obtained results suggest that a day night modulation is imposed upon the reactivity of the cingulate cortex neurons, and that daily changes in the reactivity are observed in vitro. PMID- 2894332 TI - Effects of haloperidol on neurotransmitter activity in the rat vas deferens. AB - 1. The effects of haloperidol on the responses of the isolated rat vasa deferentia to catecholamines and ACh were studied. 2. Haloperidol produced a competitive antagonism to responses elicited by NA and DA in the vas deferens. 3. The M1 and M2 muscarinic responses to ACh of the vas deferens were potentiated by this neuroleptic. 4. The AChE activity of the vas deferens was significantly depressed by pretreatment with haloperidol. 5. The ability of haloperidol to lower AChE activity was compared with that of neostigmine and it may be due to a similar molecular mechanism. 6. The present results suggest that haloperidol has anti-AChE properties that may be responsible for the potentiation of the responses to ACh. 7. The study indicates that haloperidol has a wider range of pharmacological actions than previously reported. PMID- 2894334 TI - [Expression of class II genes in regulatory T-lymphocyte populations in mice and the possible mechanism of genetic restriction of region I of the H-2 complex]. AB - Some contradictions exist in molecular and classical mapping of genes controlling I-J and I-AT (Iat) determinants of the T suppressor and T helper murine lymphocytes. There is strong evidence in favour of the hypothesis that lat molecules function as components of the T receptor for self Ia proteins in a I restricted manner. These data are discussed from the point of view that beta genes of the I region of the H-2 complex may control Iat determinants of regulatory T lymphocytes' receptors. A hypothesis is proposed that the I-region determined restriction is based on interactions between alpha-chains of Ia molecules on A cells and beta-chains of receptors on T lymphocytes. PMID- 2894333 TI - Effects of ethacrynic acid and cystamine on sodium nitroprusside-induced relaxation, cyclic GMP levels and guanylate cyclase activity in rat aorta. AB - 1. Ethacrynic acid, an agent that alkylates sulfhydryl residues, inhibited sodium nitroprusside- and 8-bromo cyclic GMP-induced relaxations. 2. Sodium nitroprusside-induced increased levels of cyclic GMP were unaltered by ethacrynic acid. 3. Concentrations of ethacrynic acid that inhibited sodium nitroprusside induced relaxation did not affect sodium nitroprusside-activation of crude soluble and particulate fractions of guanylate cyclase, while a higher concentration of ethacrynic acid did inhibit the activation. 4. Cystamine, an agent that oxidizes sulfhydryl residues, inhibited sodium nitroprusside activation of crude soluble and particulate fractions of guanylate cyclase. Exposure of intact rat aorta to cystamine inhibited basal guanylate cyclase activity in the particulate fraction but, in general, not in the soluble fraction. 5. These results are consistent with the hypothesis that vascular smooth muscle relaxation requires sulfhydryl groups. The sulfhydryl groups that presumably are alkylated by ethacrynic acid are not contained within guanylate cyclase and are involved at a regulatory step after the formation of cyclic GMP. The sulfhydryl groups altered by cystamine may be located on particulate guanylate cyclase and a role for particulate guanylate cyclase in nitrovasodilator-induced relaxation needs to be examined further. PMID- 2894335 TI - Structural analysis of the pilE region of Neisseria gonorrhoeae P9. AB - We have determined the nucleotide sequence of an expressed structural pilus gene (pilE) derived from Neisseria gonorrhoeae strain P9-2. Detailed analysis of nucleotide sequences upstream from pilE revealed a silent, truncated pilin gene segment that was linked to families of DNA elements (RS1 and RS3) that have previously been identified at the major silent pilin gene locus (pilS1) and at pilE of the independently isolated N. gonorrhoeae strain MS11ms. A nucleotide sequence downstream from pilE was reminiscent of the recognition sequences of several recombinases, including Tn3 tnpR product (resolvase), suggesting a possible role for site-specific events in the recombinational modulation of pilus expression. PMID- 2894336 TI - Somatostatin does not reduce oesophageal variceal pressure in liver cirrhotics. AB - Transmural oesophageal variceal pressure was determined by direct puncture of the varices in 27 patients with liver cirrhosis and oesophageal varices. Variceal pressure was not influenced three to six minutes after somatostatin bolus administration and slightly increased during somatostatin infusion. Thus, potential haemostatic benefits of somatostatin cannot be explained by pressure reductions in the varices. PMID- 2894338 TI - Dose-response and time-response biochemical and histological study of potassium dichromate-induced nephrotoxicity in the rat. AB - This study provides quantitative toxicological data on potassium dichromate induced renal damage and considers the possible difficulties arising from the non invasive in vivo assessment of renal damage, with particular attention to enzymuria. Renal damage induced in male Wistar rats by single sc injections of potassium dichromate was assessed 52 to 72 hr after doses ranging from 3 to 20 mg potassium dichromate/kg body weight and throughout a 9-day period following a dose of 20 mg potassium dichromate/kg. The earliest and most sensitive non invasive functional change in the dose-response and time-response studies was an elevation in the rate of urinary excretion of protein. Evidence of tissue damage was observed with elevations in the urinary excretion rates of the brush border enzymes, gamma-glutamyltransferase, alkaline phosphatase and leucine aminopeptidase, the cytosolic enzymes, aspartate aminotransferase and lactate dehydrogenase and the lysosomal enzyme, N-acetyl-beta-D-glucosaminidase. Such changes occurred as early as the abnormal urinary protein excretion, but returned to control or sub-control values sooner. Urinary brush border enzyme excretion returned to control values within 48 hr following potassium dichromate injection, despite histological and histochemical evidence of extensive renal damage and renal dysfunction. Elevations in plasma aspartate aminotransferase and lactate dehydrogenase levels were observed, but histochemical and isoenzyme studies would be needed to determine the source of these increases. The simplest and most persistent indicators of renal damage were the urinary excretion of protein and N acetyl-beta-D-glucosaminidase. PMID- 2894337 TI - Influence of ulcer healing agents on ulcer relapse after discontinuation of acute treatment: a pooled estimate of controlled clinical trials. AB - Whether or not the incidence of ulcer relapse varies according to the drug used to produce initial healing is a controversial matter. We tackled this problem using data from 15 eligible trials from 25 published controlled trials in patients followed up for six to 12 months. Pooled estimates of differences in ulcer relapse incidence between patients initially healed with H2-antagonists and patients initially healed with non-H2-antagonist drugs were calculated. The overall incidence of relapse in patients healed with comparator drugs is 11 percentage units lower at six and 12 months, than that observed in H2-antagonist healed patients. The confidence intervals are +/- 8% at six months and +/- 7% at 12 months. These data suggest the existence of a different effect on relapse incidence for the entire class of comparator drugs taken as a whole, compared with H2-antagonists. On considering the non-H2-antagonists singly, this conclusion holds good only in the case of tripotassium dicitrato bismuthate. PMID- 2894339 TI - Alpha-adrenoceptor blockade by phentolamine inhibits beta-adrenergically and cholinergically induced glucagon secretion in the mouse. AB - Glucagon secretion is known to be stimulated by activation of the alpha adrenoceptors. In this study, we investigated whether alpha-adrenoceptor blockade by phentolamine affects basal and stimulated glucagon secretion in the mouse. Phentolamine was injected intraperitoneally to mice at dose levels varying from 2.6 to 260 mumol/kg. It was found that, while decreasing plasma glucose levels, phentolamine did not over this wide dose range affect basal glucagon concentrations indicating an inhibition of the hypoglycaemia-induced glucagon secretion. Further, phentolamine clearly inhibited the glucagon secretory response to beta-adrenergic or cholinergic stimulation. Thus, phentolamine (2.6 mumol/kg), impaired the glucagon secretory response to the beta 2-adrenoceptor agonist terbutaline by 51% (P less than 0.01), and to the cholinergic agonist carbachol by 44% (P less than 0.02). We conclude that alpha-adrenoceptor blockade by phentolamine inhibits the glucagon secretion following hypoglycaemia or stimulation by beta-adrenergic and cholinergic agonists. Thus, the alpha adrenoceptors seem to be of great importance for glucagon secretion in the mouse. PMID- 2894340 TI - The effect of dopaminergic blockade on thyrotrophin response to thyrotrophin releasing hormone and somatostatin. AB - Using a large number of animals we have been able to demonstrate that somatostatin administration (20 micrograms/100 g bw) significantly reduces both basal serum thyrotrophin (TSH) levels and the response to thyrotrophin-releasing hormone (TRH) in the normal rat. Pretreatment with the dopaminergic antagonist domperidone resulted in increased TSH levels, increased response to TRH but no modification in the response to somatostatin. PMID- 2894341 TI - Comparison of metabolic and hormonal effects of calcitonin and somatostatin (SRIF) in the course of oral glucose tolerance test (OGTT). AB - A comparison is presented of the effect of two therapeutic doses of synthetic somatostatin (250 and 500 micrograms) and salmon calcitonin (50 and 100 U) on the blood levels of sugar, insulin (IRI), somatotropin (HGH) and cortisol in healthy volunteers following peroral administration of 75 g of glucose. Calcitonin was responsible for a significant change in glycaemia as well as IRI levels: following a retarded enhancement glycaemia as well as insulinaemia through out the first 15-30 minutes of OGTT, increased levels of both indicators were persistent at minute 120 and 180, so that the course of both curves was almost parallel. The effect was similar after SRIF had been administered, with the exception of insulin secretion being more pronounced, so that at a later stage of OGTT no hyperinsulinaemia was seen. The HGH levels tended to decrease due to both hormones, the tendency being more marked after SRIF, though statistically insignificant. There was a marked difference between the hormones as regards their effect on adrenocortical secretion. While the latter was constantly stimulated throughout OGTT under calcitonin infusion, the influence of SRIF was not significant. The metabolic and hormonal changes were found after both a lower and higher dose of both hormones, the only differences being that the inhibitory effect on the initial increase in glycaemia following a lower dose of SRIF was of no statistical significance. Hence, the metabolic and hormonal effects of calcitonin and SRIF in an acute experiment display many similarities, however, they do differ in some aspects; these effects do not depend on the doses demonstrated for both lower and higher doses of the above hormones. PMID- 2894342 TI - Synchronous duodenal neuroendocrine tumours in von Recklinghausen's disease--a case report of co-existing gangliocytic paraganglioma and somatostatin-rich glandular carcinoid. AB - The co-existence of a gangliocytic paraganglioma and a glandular psammomatous carcinoid in the duodenum of a patient with von Recklinghausen's disease and bilateral phaeochromocytomas is reported. The two lesions were considered to be distinctive by light microscopy, electron microscopy and immunocytochemistry. The cells of the glandular carcinoid showed strong cytoplasmic immunoreactivity for somatostatin and contained only scanty intracytoplasmic microfilaments on electron microscopy. In contrast, the endocrine cells of the gangliocytic paraganglioma were positive for pancreatic polypeptide and serotonin, were negative for somatostatin, and contained conspicuous intracytoplasmic aggregates of filaments. The histogenic relationship between the two tumours is discussed. This case strengthens the known association of glandular duodenal somatostatinoma with von Recklinghausen's disease and phaeochromocytoma and, in the light of a previous case report, suggests that von Recklinghausen's disease and gangliocytic paraganglioma may co-exist more commonly than expected. PMID- 2894343 TI - Linkage disequilibrium analyses and restriction mapping of four RFLPs at the pro alpha 2(I) collagen locus: lack of correlation between linkage disequilibrium and physical distance. AB - Restriction fragment length polymorphisms (RRLPs) located at short distances may demonstrate linkage disequilibrium. Under the assumption that the distances between the loci of the RFLPs are inversely related to the linkage disequilibria, gene order may be deduced. However, if the assumption is invalid, the results may be incorrect. We have studied four different DNA polymorphisms at the COLIA2 locus in 180 unrelated Norwegian individuals. Observed frequencies (presence/absence) for the different polymorphic sites were as follows: site A (EcoRI) 0.30/0.70, site B (MspI) 0.83/0.16, site C (StuI) 0.86/0.14, and site D (RsaI) 0.66/0.34. Of 16 possible haplotypes 12 were demonstrated, and 2 additional were deduced to be present. Restriction mapping of the four polymorphic sites gave the following order of the sites from the 5' to the 3' of the gene: A-D-B-C. Linkage disequilibrium was not found between the sites A and D; strong disequilibrium was found between sites A and C, and B and C; and less strong, between A and B, B and D, and C and D. Analysis of linkage disequilibrium coefficients between all pairs of loci demonstrated that there is no consistent relationship between linkage disequilibrium and physical distance (tau = -0.07). These results suggest that for a small region of the genome, factors such as deviating mutation rate and gene conversion may add significantly to rearrangements by recombination. Thus, a deduced gene order from linkage disequilibrium data has to be regarded with great caution. PMID- 2894346 TI - Homozygous osteogenesis imperfecta unlinked to collagen I genes. AB - In a consanguineous pedigree in which a severe type of osteogenesis imperfecta was segregating as an autosomal recessive trait, analysis of genetic markers for both collagen I structural loci COL1A1 and COL1A2 showed that the phenotype was unlinked to either locus. PMID- 2894345 TI - DNA linkage analysis of X-linked retinoschisis. AB - Four families with juvenile retionoschisis (RS) have been studied by linkage analysis utilizing eleven polymorphic X-chromosomal markers. The results suggest a close linkage between DXS43, DXS41, and DXS208 and the RS locus at Xp22. The RS locus is distal to the OTC locus, DXS84, and the DMD locus but proximal to DXS85. No recombination events were observed between the RS locus and DXS43 and DXS41. The maximum likelihood estimate of the recombination fraction (theta) was thus zero and the peak lod scores (z) were 4.98 (DXS43) and 4.09 (DXS41). The linkage data suggest that the gene order on Xp is DXS85-(DXS43, RS, DXS41)-DMD-DXS84-OTC. PMID- 2894344 TI - Deletion proximal to DXS68 locus (L1 probe site) in a boy with Duchenne muscular dystrophy, glycerol kinase deficiency, and adrenal hypoplasia. AB - We report a case of a boy with Duchenne muscular dystrophy (DMD) associated with GK deficiency (GK), congenital adrenal hypoplasia (AHC), and mental retardation. Cytogenetic analysis of prometaphasic chromosomes revealed an interstitial chromosome deletion at Xp21.2 possibly extending to Xp21.1 or Xp21.3. His phenotypically normal mother was heterozygous for this deletion. DNA probe analysis on Southern blots showed that the deletion affected the following probe sites: 754, pERT 84, 21A, XJ2.3, pERT 87, JBir, and J66-H1, whereas L1, C7, and CX5.4 probes gave a normal signal. Pulse field gel electrophoresis after SfiI digestion did not show abnormal fragments with L1. These data are consistent with a deletion of about 4 megabases and indicate that the GK and AHC loci are proximal to L1 and distal to J66-H1. PMID- 2894347 TI - A PvuII polymorphism in the 5' flanking region of the apolipoprotein AIV gene: its use to study genetic variation determining serum lipid and apolipoprotein concentration. AB - We have used a 1.05-kb unique genomic fragment from the 5' end of the apolipoprotein (apo) CIII gene to identify a restriction fragment length polymorphism (RFLP) detected with the restriction enzyme PvuII, in the apoCIII apoAIV intergenic region. In a sample of 220 normolipidaemic individuals from the UK population, the frequency of the rare allele, VB2 is 0.054. The PvuII polymorphism is in apparent linkage equilibrium with three other RFLPs of this gene cluster, detected with the restriction enzymes XmnI, PstI and SstI, but in linkage disequilibrium with an RFLP in the apo-CIII gene also detected with PvuII. Taken together, these five RFLPs have a PIC (polymorphism information content) value of 0.8, and therefore are informative for genetic studies. Individuals with the genotype VB1VB2 had lower mean concentrations of apoAI, and HDL-cholesterol than individuals with the genotype VB1VB1. However these differences were not statistically significant. PMID- 2894348 TI - A physical map of the apolipoprotein gene cluster on human chromosome 19. AB - We have generated a restriction map around the cloned genes for human apolipoproteins CI, CII, and E by pulsed-field gel analysis. We show that the genes are clustered within an area of about 50 kb on chromosome 19. The genes are all oriented in the same direction, head to tail. PMID- 2894350 TI - Receptor systems in tissues of the nervous system. PMID- 2894351 TI - Role of immunology in defining transmitter-specific neurons. PMID- 2894349 TI - Evidence for linkage equilibrium between two RFLPs associated with the human SST locus. AB - Haplotypes were established for the alleles at the EcoRI and BamHI polymorphic restriction sites associated with the human somatostatin (SST) gene. The two genetic markers, in spite of their proximity, are in linkage equilibrium. PMID- 2894352 TI - A homozygous point mutation results in a stop codon in the C1q B-chain of a C1q deficient individual. AB - Southern blot analysis of the B-chain genes in one of eight C1q-deficient individuals revealed an abnormal banding pattern. The defect, which was homozygous, could be localized by restriction mapping to a single Taq I site within residue 150 in the coding region of the B-chain gene. DNA sequencing across the site revealed a stop codon that would cause premature termination of the protein product. No material corresponding to the A or C chains, or a truncated B chain, could be identified by antigenic analysis of the patient's serum, indicating that a complete B chain is required for secretion of a C1q molecule. PMID- 2894353 TI - Squid glycoproteins with structural similarities to Thy-1 and Ly-6 antigens. AB - In an attempt to identify invertebrate homologs of Thy-1 antigen, the optic and central nervous tissue of squid was solubilized in deoxycholate and fractionated by lentil lectin affinity chromatography and gel filtration to yield small abundant glycoproteins. Material with biochemical similarities to Thy-1 was found and shown to consist of two glycoproteins that were ultimately purified using monoclonal antibody affinity columns. Both glycoproteins were sequenced to yield sequences of 84 residues for Sgp-1 and 92 residues for Sgp-2. The sequences were analyzed for similarities to Thy-1 and other Ig-related sequences, and Sgp-1 showed some similarities that were greater than 3 standard deviation units away from mean random scores when tested with the ALIGN program. However, the sequence patterns were not typical of Ig-related domains and the relationship of Sgp-1 to the Ig superfamily remains problematical. Sgp-2 showed no relationship to the Ig superfamily, but similarities to Ly-6 antigen sequences were noted that are in accord with an evolutionary relationship. The similarities included ten Cys residues in each sequence of which eight were matched in the best alignment given by the ALIGN program. Chemical evidence was obtained for glycophospholipid tails at the COOH-termini of Sgp-1 and Sgp-2 as is the case for Thy-1 and Ly-6 antigens. PMID- 2894354 TI - Linkage relationships in the bovine MHC region. High recombination frequency between class II subregions. AB - Class II genes of the bovine major histocompatibility complex (MHC) have been investigated by Southern blot analysis using human DNA probes. Previous studies revealed the presence of bovine DO beta, DQ alpha, DQ beta, DR alpha, and DR beta genes, and restriction fragment length polymorphisms for each of these genes were documented. In the present study, the presence of three additional class II genes, designated DZ alpha, DY alpha, and DY beta, are reported. DZ alpha was assumed to correspond to the human DZ alpha gene while the other two were designated DY because their relationship to human class II genes could not be firmly established. The linkage relationships among bovine class II genes and two additional loci, TCP1B and C4, were investigated by family segregation analysis and analysis of linkage disequilibrium. The results clearly indicated that all these loci belong to the same linkage group. This linkage group is divided into two subregions separated by a fairly high recombination frequency. One region includes the C4, DQ alpha, DQ beta, DR alpha, and DR beta loci and the other one is composed of the DO beta, DY alpha, DY beta, and TCP1B loci. No recombinant was observed within any of these subregions and there was a strong or fairly strong linkage disequilibrium between loci within groups. In contrast, as many as five recombinants among three different families were detected in the interval between these subregions giving a recombination frequency estimate of 0.17 +/- 0.07. The fairly high recombination frequency observed between class II genes in cattle is strikingly different from the corresponding recombination estimates in man and mouse. The finding implies either a much larger molecular distance between some of the bovine class II genes or alternatively the presence of a recombinational "hot spot" in the bovine class II region. PMID- 2894356 TI - Pediatric emergencies. PMID- 2894355 TI - Enzymatic studies and isoenzyme pattern of gammaglutamyl transpeptidase (GGTP) in Indian childhood cirrhosis (CC). PMID- 2894357 TI - Nitrendipine in severe hypertension. Satellite symposium on calcium antagonists. AB - We report the results of a multicenter trial in which nitrendipine, alone or in combination with a diuretic, a beta-blocker, or both, was administered to 114 patients with severe hypertension (greater than or equal to 115 mm Hg). Nitrendipine was titrated in doses of 5 to 30 mg b.i.d. If blood pressure was not controlled with nitrendipine alone, hydrochlorothiazide or propranolol or both were added. After a mean of 29 days in the study, 96 (90%) of 107 patients reached the initial goal of therapy; in 44 (41%) given nitrendipine alone the mean decrease in supine blood pressure was 38/25 mm Hg. After a mean of 91 days, 69 (72%) of 96 patients achieved the final goal of therapy; in 24 (25%) patients given nitrendipine alone the mean supine blood pressure decrease from baseline was 49/33 mm Hg. Falls in blood pressure were comparable in the patients given drug combinations. Seventy-two of 114 patients given study drug(s) had adverse experiences; headache and edema were the most frequent complaints. Only four patients dropped out of the study because of adverse effects. Most abnormal laboratory values occurred when nitrendipine was given with hydrochlorothiazide or propranolol or both. Analysis of severely hypertensive patients followed up in our Virginia center revealed continued control of blood pressure after long-term follow-up (43 +/- 3 [SD] months). Average supine blood pressure was reduced from 180/121 +/- 21/5 to 140/90 +/- 16/9 (SD) mm Hg (p less than 0.001). It was concluded that the calcium antagonist nitrendipine, alone or in combination with a diuretic or beta-blocker or both, is effective in the treatment of severe hypertension. PMID- 2894358 TI - Review of salt restriction and the response to antihypertensive drugs. Satellite symposium on calcium antagonists. AB - We evaluated the response to salt restriction in hypertensive patients receiving drugs. By restricting their salt intake to less than 80 mmol of sodium per day for 3 months, 50% of patients reaching goal compliance were able to discontinue diuretics. The literature also reveals responses to a low salt diet. Salt restriction augmented the hypotensive effect of chlorthalidone in two investigations, but not in another, and the hypotensive effect of beta-blockers in three trials. Sodium intake of 10 mmol/day caused a much greater decrease in blood pressure in response to a single dose of captopril than did a sodium diet of 200 mmol/day. In patients receiving various fixed regimens for 2 months, salt restriction decreased blood pressure in all but those receiving calcium blockers. A single dose of nifedipine lowered blood pressure more in patients receiving 350 mmol of sodium per day than in the same patients given 150 or 10 mmol/day. Verapamil for 3 days was more effective in patients receiving 212 mmol of sodium per day than in the same subjects receiving 9 mmol/day. Nitrendipine caused a greater decrease in diastolic blood pressure in patients who did not reduce salt intake compared to those who did. Salt restriction appears useful in salt sensitive patients who receive beta-blockers, diuretics, converting enzyme inhibitors, or centrally acting drugs. Calcium channel entry blockers may not require salt restriction to maximize their effect. PMID- 2894359 TI - Diuresis and natriuresis during continuous dopamine-1 receptor stimulation. AB - Stimulation of renal dopamine-1 (DA1) receptors for 3 hours produces an increase in renal plasma flow and sustained natriuresis. The present study was designed to assess the response of renal hemodynamic and tubular function to long-term DA1 receptor stimulation. Fenoldopam, a selective DA1 receptor agonist, was infused intravenously for 24 hours in 10 normal male subjects in metabolic balance at 150 mEq sodium and 60 mEq potassium intake in a single-blind, vehicle-controlled protocol. During DA1 receptor activation, urine flow rate and fractional excretion of sodium increased for the first 5 hours, 16.9 +/- 0.9 ml/min compared with a vehicle control value of 12.4 +/- 0.5 ml/min (p less than 0.001) and 2.0 +/- 0.1% compared with a vehicle control value of 1.1 +/- 0.1% (p less than 0.005), respectively. Urinary sodium excretion rose at 5 hours, 0.27 +/- 0.02 mEq/min compared with a vehicle control value of 0.14 +/- 0.01 mEq/min (p less than 0.01). Renal plasma flow increased during fenoldopam at 5 hours, 505 +/- 47 ml/min compared with a vehicle control value of 397 +/- 25 ml/min (p less than 0.01), and was sustained for 24 hours, 523 +/- 40 ml/min compared with 432 +/- 31 ml/min (p less than 0.05). The distal sodium load increased and the percentage of distal sodium reabsorption decreased during fenoldopam. Glomerular filtration rate, blood pressure, heart rate, plasma aldosterone concentration, plasma renin activity, and fractional excretion of potassium were unchanged. Selective DA1 receptor activation produced sustained 5-hour diuresis and 11-hour natriuresis without kaliuresis or a systemic hemodynamic effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894361 TI - Type 1 fimbriate Escherichia coli stimulates a unique pattern of degranulation by human polymorphonuclear leukocytes. AB - Uropathogenic strains of Escherichia coli bearing mannose-sensitive (type 1) fimbriae promote a unique pattern of degranulation from human polymorphonuclear leukocytes (PMN). Significant quantities of the primary (1 degree) and tertiary (3 degree) granule markers, neutral protease-myeloperoxidase and N-acetyl-beta-D glucosaminidase, respectively, were released by PMN in a dose- and time-dependent manner when stimulated by these defined bacterial strains. Organisms bearing mannose-resistant (P) fimbriae promoted release of only the secondary (2 degree) granule marker, vitamin B12-binding protein. When this pattern of degranulation was compared to that produced by PMN in response to a variety of soluble and particulate stimuli, only the calcium ionophore A23187 similarly triggered 1 degree and 3 degree granule marker release. All the other stimuli tested- zymosan, serum-treated and unopsonized; n-formylmethionyl-leucyl-phenylalanine; and phorbol myristate acetate--promoted release of only the 2 degree granule marker. These results demonstrate selectivity of PMN degranulation in response to a number of transmembrane signals. In addition, the capacity of E. coli to promote PMN degranulation is dependent on its phenotypic fimbrial expression, a surface characteristic which correlates significantly with its relative surface hydrophobicity as measured by binding to octyl Sepharose. Those bacteria demonstrating the greatest hydrophobicity were capable of triggering discharge of all three granule marker proteins. Thus, the mannose-sensitive fimbriae of uropathogenic E. coli may contribute significantly to their potential pathophysiologic role in renal scarring. PMID- 2894360 TI - Effects of adenylate cyclase toxin from Bordetella pertussis on human neutrophil interactions with Coccidioides immitis and Staphylococcus aureus. AB - Bordetella pertussis extract that contained adenylate cyclase toxin produced large increases in human neutrophil cyclic AMP levels and inhibited their oxidative burst, as reflected by luminol-enhanced chemiluminescence and superoxide release. The adenylate cyclase toxin-containing extract blocked neutrophil-mediated inhibition of N-acetylglucosamine incorporation by arthroconidia of Coccidioides immitis in a dose-dependent fashion but had no effect on neutrophil phagocytosis of Candida glabrata and only a slight inhibitory effect on arthroconidial attachment. Neither purified pertussis toxin nor extracts from Bordetella mutants lacking the adenylate cyclase toxin affected neutrophil-mediated inhibition of arthroconidial N-acetylglucosamine incorporation. These studies indicate that adenylate cyclase toxin, alone or in concert with other B. pertussis-elaborated toxins, blocks neutrophil inhibition of arthroconidia, primarily by affecting neutrophil responses other than attachment or phagocytosis. PMID- 2894362 TI - Free fatty acids released from phospholipids are the major heat-stable hemolytic factor of Entamoeba histolytica trophozoites. AB - The major hemolytic activity of Entamoeba histolytica trophozoites is located in a vesicular fraction called P30 and known to be due to heat-labile and heat stable hemolytic components whose effect increases up to 100 times during preincubation at 36 degrees C. The heat-stable hemolytic activity (HSHA) was found in the chloroform-methanol extract of preincubated P30, whose partition with 2 M KCl yielded a lipid fraction, an interphase, and an aqueous phase. HSHA was detected only in the lipid fraction, where it amounted to 59% of the chloroform-methanol extract activity and increased 50% when supplemented with the interphase material; it was accounted for by the free fatty acids, whose potency increased 33% with the interphase material, and was blocked by delipidated bovine serum albumin. A parallel increase in free fatty acids and lysophospholipids and a corresponding decrease in phospholipids were observed during P30 preincubation. Most of the phospholipase activity of trophozoite homogenates was also found in P30. Therefore, most of the HSHA generated during preincubation was due to free fatty acids released from phospholipids by a P30 phospholipase that may contribute significantly to E. histolytica cytopathogenicity and virulence. PMID- 2894363 TI - Role of type 1 and S fimbriae in the pathogenesis of Escherichia coli O18:K1 bacteremia and meningitis in the infant rat. AB - The role of fimbriae in the pathogenesis of Escherichia coli infection was studied in the infant rat model. Rat pups were challenged intraperitoneally at the age of 5 days with E. coli K1 (strain IH3080, O18:K1:H7) and three different subpopulations (type 1, type S, or nonfimbriated) of it. All bacterial subpopulations were able to produce peritonitis, bacteremia, and meningitis. However, the type 1 fraction was the least virulent and the type S fraction was the most virulent, as judged by the bacterial counts in body fluids and by the mortality rates of the pups. Fimbrial phase variation to mainly the type-S fimbriated forms was observed in all body fluids. An initially type-S-fimbriated inoculum remained predominantly type S fimbriated in the peritoneal fluid and blood. In the cerebrospinal fluid, however, about 50% of the bacteria were type S fimbriated and 50% were nonfimbriated 1 h after challenge with the type-S fimbriated subpopulation; at later times the share of type-S-fimbriated bacteria also increased in the cerebrospinal fluid. PMID- 2894365 TI - Somatostatin treatment of psoriatic arthritis. AB - Eighteen patients with psoriatic arthritis were treated for 48 hours with an infusion of somatostatin 250 micrograms/hr diluted in a 5% glucose solution. This therapy led to a reduction of joint pain and satisfactory clearing of cutaneous lesions immediately after treatment in eight patients, less marked results in four, and null in four. Two patients were dropped from the study because of negative side effects during administration of the drug. Fifteen days after treatment, the clearing of lesions and joint pain reduction were even more pronounced. The most encouraging results were obtained on erythrodermic and large plaque psoriasis and on the polyarticular involvement. We suggest that the use of this drug, whose side effects are discussed, should be limited to patients with polyarthritis showing severe cutaneous involvement. PMID- 2894364 TI - Interaction of Escherichia coli with polymorphonuclear leukocytes in pathogenesis of urinary tract infection in mice. AB - Two type 1 fimbria-producing strains of Escherichia coli, 31-B and K12W1-3, and two type 1 fimbriae-defective mutants derived from 31-B, BH5 and BH9, were compared for their capacity to induce vesical infection in mice undergoing water diuresis and to interact in vitro with murine peritoneal exudate polymorphonuclear leukocytes (PMN). Strains 31-B and BH5 caused rapid bacterial multiplication in the bladder wall after being inoculated intrabladderly; their log-phase cells grown at 37 degrees C, in striking contrast to their stationary phase or 17 degrees C-grown cells, resisted phagocytic killing by PMN in the presence of normal murine serum. Strains K12W1-3 and BH9 failed to cause vesical infection, and their cells were always susceptible to the opsonophagocytic killing by PMN irrespective of the growth conditions. Nevertheless, the log-phase cells of the three isogenic strains, 31-B, BH5, and BH9, grown at 37 degrees C gave almost the same chemiluminescent response patterns during incubation with PMN in normal serum. The phagocytic resistance in strains 31-B and BH5 was eliminated by briefly treating bacterial cells with EDTA. These results suggest that the two virulent strains may express an antiphagocytic activity during their growth in the bladder and continue to stimulate the oxidative metabolic burst of PMN without being ingested and killed, and that the antiphagocytic activity may be related to a bacterial surface component(s) that is removed by EDTA. PMID- 2894366 TI - Effect of sodium 2-n-pentadecyl-benzimidazole-5-carboxylate (M & B 35347B), an inhibitor of acetyl-CoA carboxylase, on lipogenesis and fat deposition in obese hyperglycaemic (ob/ob) and lean mice. AB - A high rate of lipogenesis in obese mice plays a major role in their excessive deposition of body lipid. Inhibition of lipogenesis may decrease their obesity. Therefore, we have investigated the effects of sodium 2-n-pentadecyl benzimidazole-5-carboxylate (M & B 35347B), an inhibitor of acetyl-CoA carboxylase, on in-vivo lipogenesis in obese and lean mice. It significantly inhibited hepatic cholesterol and fatty acid synthesis, measured using 3H2O, in both lean and obese mice, with or without a glucose load. Brown adipose tissue (scapular) lipogenesis was decreased by M & B 35347B in obese mice but not in lean mice. In white adipose tissue, M & B 35347B did not affect the rates of lipogenesis in either scapular white, inguinal or epididymal depots of obese mice, or the inguinal and scapular white depot of lean mice. However, it doubled lipogenesis in the epididymal fat pad of lean mice. After a glucose load, lipogenesis in the lean epididymal fat pad was not inhibited but that in the inguinal depot was. M & B 35347B inhibited acetyl CoA carboxylase of adipose tissue in vitro but only a small inhibition was detected after in-vivo treatment. These different responses according to type of mouse, treatment and tissue site appear to stem from differences in inhibitor concentration and the importance of acetyl CoA carboxylase as the rate-limiting enzyme of lipogenesis. The weight gain of obese mice dosed orally (200 mg M & B 35347B/kg daily) for 60 days was unaffected and they continued to deposit excess body fat. This presumably occurred because of the lack of inhibition of fatty acid synthesis in white adipose tissue. PMID- 2894367 TI - Thermogenic agents in the treatment of human obesity: preliminary results. PMID- 2894368 TI - Increase in activity and biosynthesis of phospholipase A of Entamoeba histolytica by cholesterol passage. PMID- 2894369 TI - Neuroendocrine correlates of the type A behavior pattern: a review and new hypotheses. AB - Various studies have tried to identify the possible neuroendocrine correlates of the action/emotion complex defined as Type A behavior pattern. Type A subjects have been observed quite consistently to respond to laboratory stressors with a greater sympathetic nervous system response than Type B subjects. There also seems to be a trend towards a hyperactivity of the hypothalamic-pituitary adrenocortical axis in Type A individuals. The clinical relevance of these findings lies in the fact that there is an increasing clinical and laboratory evidence of a pathogenic role of catecholamines in coronary artery disease (CAD) and that some of these neuroendocrine correlates might actually be the mediators of the risk of CAD conferred by the Type A behavior pattern. We hypothesize that dehydroepiandrosterone-sulfate (DHEA-S), an adrenal weak androgen, is inversely correlated with the degree of Type A behavior pattern and this hypothesis seems to be confirmed by the results of a preliminary investigation that we have conducted. PMID- 2894370 TI - gamma-Glutamyl transpeptidase demonstrated in tissue sections embedded in glycol methacrylate resin. AB - A method is described for the histochemical demonstration of gamma-glutamyl transpeptidase in tissue sections embedded in glycol methacrylate at low temperature. Enzyme activity was preserved by a short (3 h) fixation of tissue in 4% paraformaldehyde at 4 degrees C prior to embedding at 4 degrees C. Tissue embedded in glycol methacrylate combined good morphology with accurate enzyme localization. Blocks of the embedded tissue could be stored at room temperature for at least 3 months without loss of enzyme activity. The resin is non fluorescent, allowing the use of the fluorescent coupling agent 5 nitrosalicylaldehyde to visualize the reaction product. PMID- 2894371 TI - Expression of the unc genes in Escherichia coli. AB - The unc (or atp) operon of Escherichia coli comprises eight genes encoding the known subunits of the proton-translocating ATP synthase (H+-ATPase) plus a ninth gene (uncI) of unknown function. The subunit stoichiometry of the H+-ATPase (alpha 3 beta 3 gamma 1 delta 1 epsilon 1 a1b2c10-15) requires that the respective unc genes be expressed at different rates. This review discusses the experimental methods applied to determining how differential synthesis is achieved, and evaluates the results obtained. It has been found that the primary level of control is translational initiation. The translational efficiencies of the unc genes are determined by primary and secondary mRNA structures within their respective translational initiation regions. The respective rates of translation are matched to the subunit requirements of H+-ATPase assembly. Finally, points of uncertainty remain and experimental strategies which will be important in future work are discussed. PMID- 2894372 TI - Molecular genetics of F1-ATPase from Escherichia coli. AB - We have reviewed recent molecular biological studies on F1-ATPase of Escherichia coli and emphasized the advantages of using the bacterium in studies on this important enzyme. All subunits had homologies of varied degrees with those from other organisms. Mutations of F1 subunits caused defects in catalysis and assembly. Defects of the mutant enzymes were studied extensively together with the determination of the amino acid substitutions. Extensive molecular biological studies may help greatly in understanding the normal mechanism and assembly of the complex. PMID- 2894373 TI - Atrial natriuretic peptide binding, cross-linking, and stimulation of cyclic GMP accumulation and particulate guanylate cyclase activity in cultured cells. AB - The stimulation of cyclic GMP accumulation and particulate guanylate cyclase activity by atrial natriuretic peptide (ANP) was compared to the affinity and number of ANP receptors in eight cultured cell types. At 100 nM, ANP increased cyclic GMP by 13-fold in bovine adrenal cortical, 35-fold in human lung fibroblast, 58-fold in canine kidney epithelial, 60-fold in bovine aortic smooth muscle, 120-fold in rat mammary epithelial, 260-fold in rat Leydig, 300-fold in bovine kidney epithelial, and 475-fold in bovine aortic endothelial cells. ANP (1 microM) increased particulate guanylate cyclase activity by 1.5-, 2.5-, 3.1-, 3.2 , 5.0-, 7.0-, 7.8-, and 8.0-fold in bovine adrenal cortical, bovine aortic smooth muscle, human lung fibroblast, canine kidney epithelial, rat mammary epithelial, rat Leydig, bovine kidney epithelial, and bovine aortic endothelial cells, respectively. Specific 125I-ANP binding to intact rat Leydig (3,000 sites/cell; Kd = 0.11 nM), bovine aortic endothelial (14,000 sites/cell; Kd = 0.09 nM), bovine adrenal cortical (50,000 sites/cell; Kd = 0.12 nM), human lung fibroblast (80,000 sites/cell; Kd = 0.32 nM), and bovine aortic smooth muscle (310,000 sites/cell; Kd = 0.82 nM) cells was saturable and high affinity. No specific and saturable ANP binding was detected in bovine and canine kidney epithelial and rat mammary epithelial cells. Two ANP-binding sites of 66,000 and 130,000 daltons were specifically labeled by 125I-ANP after cross-linking with disuccinimidyl suberate. The 130,000-dalton ANP-binding sites bound to a GTP-agarose affinity column, and the specific activity of guanylate cyclase was increased by 90-fold in this fraction. Our results demonstrate that the increase in cyclic GMP accumulation and particulate guanylate cyclase activity by ANP does not correlate with the affinity and number of ANP-binding sites. These results suggest that multiple populations of ANP receptors exist in these cells and that only one receptor subtype (130,000 daltons) is associated with particulate guanylate cyclase activity. PMID- 2894375 TI - Expression of neutral endopeptidase (enkephalinase) in heterologous COS-1 cells. Characterization of the recombinant enzyme and evidence for a glutamic acid residue at the active site. AB - Neutral endopeptidase (EC 3.4.24.11) is an integral membrane protein found in the plasma membrane of many cell types. The cDNA coding for the complete primary structure of neutral endopeptidase has recently been cloned and sequenced (Devault, A. Lazure, C., Nault, C., Le Moual, H., Seidah, N. G., Chretien, M., Kahn, P., Powell, J., Mallet, J., Beaumont, A., Roques, B. P., Crine, P., and Boileau, G. (1987) EMBO J. 6, 1317-1322). Comparison of the sequence of neutral endopeptidase with that of thermolysin, a bacterial Zn-metalloendopeptidase, suggests that Glu-584 in neutral endopeptidase probably corresponds to Glu-143 in thermolysin, which is an essential amino acid involved in catalysis. To test directly the importance of Glu-584 in the catalytic activity of neutral endopeptidase by site-directed metagenesis, we have constructed an expression vector in which the rabbit kidney cDNA encoding the entire neutral endopeptidase sequence is introduced downstream from the SV40 virus early promotor. After transfection in COS-1 monkey kidney cells, this vector was found to promote the expression of a protein with biochemical and catalytic properties identical to kidney neutral endopeptidase. Oligonucleotide-directed mutagenesis of Glu-584 to either valine or aspartic acid completely abolished the enzymatic activity of the recombinant protein without changing its affinity for the substrate-related tritiated inhibitor [3H]N-[(2R,2S)-3-hydroxyamino-carbonyl-2-benzyl-1-oxopropyl] glycine. This observation clearly identifies Glu-584 as one of the important residues responsible for the catalytic activity of the enzyme. PMID- 2894374 TI - Decrease in transforming growth factor-beta binding and action during differentiation in muscle cells. AB - We report here the effects of differentiation on the binding and action of transforming growth factor-beta (TGF-beta) in three lines of myogenic cells. In two lines (L6-A1 and C2) which irreversibly differentiate by fusing to form postmitotic myotubes, there is a virtual disappearance of TGF-beta binding sites as differentiation occurs. Analyses of the binding curves by the method of Scatchard indicates that there is little or no change in affinity but a substantial decrease in the number of binding sites. In L6-A1 cells, responsiveness to TGF-beta decreases in parallel to the loss of receptors. The decreases in TGF-beta binding and activity with differentiation are not paralleled by similar changes in another growth factor, insulin-like growth factor-I, which exhibits little change in binding and only a modest decrease in activity as L6-A1 myoblasts differentiate to form myotubes. In a third cell line (BC3H1), which exhibits reversible differentiation without fusion, there is little or no change in TGF-beta binding as the cells differentiate. Comparisons with reported decreases in binding of fibroblast and epidermal growth factors indicates that there are substantial differences in growth factor binding and actions as muscle cells differentiate, but it is not possible to make the simple generalization that differentiation is accompanied by a decrease in binding of all growth factors. PMID- 2894376 TI - Epidermal and hair follicle transglutaminases. Partial characterization of soluble enzymes in newborn mouse skin. AB - Treatment of skins of newborn mice with the neutral protease Dispase in order to separate dermis and epidermis causes pronounced changes in the levels of transglutaminase activity in the epidermis. Two soluble transglutaminases, one anionic enzyme and one cationic enzyme, of Mr approximately 90,000 and approximately 50,000, respectively, are extracted from epidermis; and the activities of both enzymes increase as a function of the time of Dispase treatment of skin. When the anionic Mr approximately 90,000 enzyme is incubated with Dispase after its chromatographic isolation from epidermal extracts, it is converted to a lower molecular weight enzyme. Hair follicles isolated from dermis prepared by a 12-h Dispase treatment of the skin of newborn mice contain two soluble cationic transglutaminases, one of which is indistinguishable from that of epidermis and the other which is not seen in epidermis. Both of these hair follicle enzymes are of Mr approximately 50,000 and appear to exist in monomeric form. They have been partially purified. Based upon these findings, we suggest that transglutaminase processing and control occur during normal differentiation of keratinocytes in epidermis and of hair follicle epidermal cells in dermis and that production of the proper forms of the enzyme may be essential to the formation of mature cornified envelopes and hair shafts, respectively. PMID- 2894377 TI - Affinity-based chromatography utilizing genetically engineered proteins. Interaction of Bordetella pertussis adenylate cyclase with calmodulin. AB - An engineered calmodulin differs from vertebrate calmodulin in its ability to activate Bordetella pertussis adenylate cyclase, and this difference has been utilized as the basis for a new purification protocol for the adenylate cyclase. VU-8 calmodulin, in which 3 glutamic acid residues (residues 82-84) have been substituted with 3 lysine residues, has a 1000-fold lower apparent affinity for the adenylate cyclase, compared to vertebrate calmodulin, and decreased maximal activity. Because of the relatively calcium-independent nature of the interaction between calmodulin and the cyclase, the use of calmodulin-Sepharose conjugates in the purification of the cyclase requires the use of chaotropic agents for elution. However, when immobilized VU-8 calmodulin was tested as a calcium dependent, affinity-based, adsorption chromatography step in the purification of the cyclase from culture media or bacterial extracts, the enzyme bound to the column in a calcium-dependent manner, and a nearly homogeneous enzyme was obtained in high yield. These results demonstrate the feasibility of using engineered calmodulins that have selective differences in activity for the rational design of rapid purification protocols for calmodulin-binding proteins as well as indicate the importance of the conserved negative charge cluster at residues 82-84 of calmodulin for activation of this cyclase. PMID- 2894378 TI - In vivo phosphorylation of clathrin-coated vesicle proteins from rat reticulocytes. AB - We have studied the in vivo phosphorylation of clathrin-coated vesicle proteins from rat reticulocytes. The major 32P-labeled polypeptides of clathrin-coated vesicles isolated from metabolically labeled cells were the the 165-, 100-110-, and 50-kDa polypeptides of the assembly protein, the clathrin beta-light chain, and to a lesser extent the clathrin alpha-light chain. The phosphorylation of the assembled (particulate) and unassembled (soluble) pools of clathrin and assembly protein was compared by immunoprecipitating the respective protein complexes from particulate and soluble cell fractions. Although all the phosphorylated polypeptides were present in both fractions, the extent of labeling was protein and fraction specific: the apparent specific activities of the assembly protein 50-kDa polypeptide and clathrin light chain were higher in the unassembled pool, whereas those of the 100-110-kDa polypeptides were higher in the assembled pool. The amino acids and polypeptide fragments labeled in vivo appeared similar to those labeled in vitro. PMID- 2894379 TI - Traumatic partial foot amputations in adults. A long-term review. AB - A retrospective study of 260 industrial amputees was undertaken to determine the long-term functional results of partial foot amputations following trauma. Follow up ranged from 1 to 68 years with a mean of 16 years. Of 113 partial foot amputees (118 amputations) who had retained their original amputation, the functional end-results were 43% good, 38% fair and 19% poor. Lisfranc and Chopart amputations were better than those at transmetatarsal or digital levels. Of 260 initial amputations 49 (19%) were revised to a Syme's or a below-knee amputation. PMID- 2894381 TI - Out-patient use of beta-blocking agents--prescribing preferences of physicians in training. AB - Beta-blocking agents are among the most frequently prescribed medications. To investigate the factors that influence their use we analysed the practices of 25 medical residents who provided longitudinal care in the out-patient clinics of a teaching hospital. A computer-based audit identified the 349 patients treated with one of four beta-blocking agents during a 4-month period. The most frequently prescribed was atenolol (48%), followed by metoprolol (28%), propranolol (20%), and nadolol (4%). Ease of use and compliance and continuation of a beta-blocker prescribed by a previous physician emerged as the most influential factors. In contrast, cost of drugs, manufacturers' promotions and advertisements had no significant influence on beta-blocker selection. PMID- 2894380 TI - Recent advances in pharmaceutical chemistry--review. III. A new wave of beta blockers. PMID- 2894382 TI - Development of somatostatin immunoreactive neurons in the rat occipital cortex: a combined immunocytochemical-autoradiographic study. AB - The postnatal development of somatostatin (SRIF)-immunoreactive neurons, previously labeled with [3H]thymidine on embryonic days E14-E22, has been studied in the rat occipital cortex. Immunocytochemistry combined with autoradiography showed an "inside-out" maturation pattern. Only SRIF neurons generated at E14 were present in layer VI in newborn rats. Later generated SRIF neurons appeared progressively higher in the cortex until about postnatal day 12 when SRIF neurons from E21 appeared in layer II. At 2 weeks of age, therefore, all SRIF neurons from E14-E21 were present. Most of these had been generated between E15 and E17 with a moderate number at E14 and rapidly diminishing numbers from E18 to E21. Although an overall layered distribution was apparent at peak production, there was a tendency for diffuse distribution most noticeable at E17. Diffusely distributed neurons were more likely to be below their appropriate layer than above it, thus contributing extra SRIF neurons to layer VI. At 3, 4, and 5 weeks, progressively fewer SRIF neurons were seen with a consequent reduction in the number of double-labeled neurons. It is suggested that the transient population of SRIF neurons thus revealed plays a role in cortical development. PMID- 2894383 TI - Circulating antibody detection in human serum to mosquito salivary gland proteins by the avidin-biotin-peroxidase technique. AB - Serum was collected from individuals with little, average, or extensive exposure to mosquito bites for determination of the presence of circulating antibodies to mosquito salivary gland proteins. Intensity of exposure was determined by mosquito-bite and exposure history. Sections cut through the thorax of four different species of mosquitoes, locally prevalent in South Florida, were exposed to serum and developed for antibody binding with the use of the avidin-biotin peroxidase immunohistochemical technique. In subjects with histories of little or average exposure to mosquitoes, binding was observed that appeared to be species specific; in subjects with extensive exposures, little antibody binding to salivary gland was noted. We hypothesize that suppression of the humoral immune response is an adaptive mechanism in response to significant exposures of mosquito salivary gland antigens. PMID- 2894384 TI - Does adult T-cell leukemia/lymphoma belong to the cutaneous T-cell lymphoma category? PMID- 2894385 TI - Increased dopamine-beta-hydroxylase-like immunoreactivity in non-noradrenergic axons supplying the guinea-pig uterine artery after 6-hydroxydopamine treatment. AB - We have reinvestigated the immunohistochemistry of autonomic axons supplying the guinea-pig uterine artery to determine whether non-noradrenergic paracervical ganglion neurons projecting to the artery contain immunoreactivity to dopamine beta-hydroxylase (DBH) or somatostatin (SOM) in addition to neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP). In untreated arteries no VIP axons had immunoreactivity to tyrosine hydroxylase (TH), although 9% had immunoreactivity to DBH. Somatostatin immunoreactivity was detected in 25% of non-noradrenergic axons containing NPY and VIP. After in vivo treatment with 6-hydroxydopamine (6 OHDA), noradrenergic axons containing immunoreactivity to NPY, DBH and TH were absent from the adventitia-medial junction. However, 65-70% of the non noradrenergic axons with NPY and VIP showed DBH immunoreactivity after 6-OHDA. These axons did not show catecholamine fluorescence after incubation with pargyline together with noradrenaline, dopamine or L-DOPA. The number of axons with SOM immunoreactivity increased by 44% after 6-OHDA treatment, but only 24% of SOM axons had DBH immunoreactivity. Surgical destruction of the non noradrenergic autonomic axons in 6-OHDA-treated animals led to the loss of all DBH immunoreactivity. These results demonstrate that DBH immunoreactivity can be detected in a small proportion of non-noradrenergic axons supplying uterine arteries from untreated animals. After chemical sympathectomy with 6-OHDA, the levels of DBH immunoreactivity in axons of non-noradrenergic neurons increased, and more axons with DBH immunoreactivity were detected. DBH immunoreactivity seemed to increase preferentially in axons with NPY and VIP, but not SOM. The number of NPY, VIP axons containing SOM also increased after 6-OHDA. These findings demonstrate that peripheral neurons containing several different potential neurotransmitters can change their levels of neuropeptides and transmitter-synthesizing enzymes in response to local environmental changes. PMID- 2894386 TI - Co-existence of neuropeptides in sympathetic, cranial autonomic and sensory neurons innervating the iris of the guinea-pig. AB - We have used double-labelling immunofluorescence to identify the peptide content of autonomic and sensory neurons innervating the iris of albino guinea-pigs. Four major classes of neurons were identified on the basis of their distributions, origins and immunohistochemical characteristics. A dense plexus of noradrenergic axons in the constrictor and dilator muscles of the iris originated from the superior cervical ganglion, and contained immunoreactivity (IR) to both neuropeptide Y (NPY) and dynorphin (DYN). The constrictor and dilator muscles were also supplied with a dense plexus of axons with IR to substance P (SP). These axons probably originated from SP-IR nerve cell bodies located along the ciliary nerves, and are almost certainly the same axons as those producing cholinergic pupilloconstriction. The iris was also innervated by unmyelinated, capsaicin-sensitive axons with IR to both SP and calcitonin gene-related peptide. Most of these axons also contained IR to DYN and some were also IR for cholecystokinin. These axons are almost certainly sensory. Axons containing IR to both NPY and vasoactive intestinal peptide (VIP) were common in the ciliary processes, and also formed a sparse plexus near the ciliary margin of the dilator muscle. Following surgical sympathetic denervation these axons showed IR for dopamine-beta-hydroxylase; they seemed to originate from the sphenopalatine ganglion. These results demonstrate that there are well-defined patterns of coexistence of neuropeptides in the autonomic and sensory neurons supplying the iris of guinea-pigs. To understand the physiological roles of these peptides, it will be necessary to consider the possibility of complex interactions between them. PMID- 2894387 TI - Pictorial analysis--computed tomography of trauma to the ankle and hindfoot. AB - A pictorial overview of the utility of computed tomography in the diagnosis and characterization of traumatic lesions affecting the ankle and hindfoot is provided. The technique is of particular importance in the setting of triplane, calcaneal, and talar fractures as well as tibiotalar and subtalar dislocations. PMID- 2894388 TI - Studies on insulin secretion by monolayer cultures of normal and tumorous human pancreatic cells. Effects of glucose, somatostatin and SMS 201-995. AB - Recently, somatostatin analogs have been introduced which can be used clinically in the treatment of tumorous or functional hypoglycemia. In the present study we investigated in vitro the regulation, the degree of autonomy and the sensitivity to natural somatostatin and its analog SMS 201-995 of insulin secretion by monolayer cultures of human pancreatic cells obtained from patients with insulinomas and from a newborn with nesidioblastosis. All cultures released insulin upon the addition of dibutyryl-cAMP and calcium, demonstrating their intact viability. Insulin secretion from nontumorous pancreatic cells surrounding an insulinoma was dose-dependently stimulated by glucose. In contrast, insulin release by B cells from a patient with nesidioblastosis and from 2 insulinomas was not stimulated by the addition of glucose. Native somatostatin (SRIF) and the synthetic analog SMS 201-995 inhibited insulin secretion from all cultures. The inhibitory effects of SRIF and SMS in the culture from the nesidioblastosis tissue, could be reversed by the addition of 11.2 mmol glucose/l, but not in one of the insulinoma cultures. This demonstrates that some sensitivity to glucose is present in B cells from the nesidioblastosis tissue, despite the unresponsiveness to glucose alone. Insulin release by insulinoma cells was blocked by somatostatin, while it was inhibited to some extent only in the cultures of nontumor B cells and of cells from the nesidioblastosis tissue. In conclusion, it was shown that insulin release by the cultured B cells obtained from several pathological conditions differed with regard to the autonomy of hormone release (glucose sensitivity) and the sensitivity to somatostatin and its analog. PMID- 2894389 TI - Acute effect of glibenclamide upon red cell transglutaminase activity in diabetic patients. AB - The acute effect of glibenclamide, a hypoglycemic sulfonylurea, upon transglutaminase activity was investigated in 6 type II diabetic patients by perfusing 1 mg glibenclamide during 1 h. Blood samples were drawn 0, 10, 20, 30, 60 min during and 30 and 60 min after perfusion to determine insulin, glucose and transglutaminase activity. No significant modifications in plasma insulin, plasma glucose and transglutaminase activity in red cells was induced by glibenclamide perfusion. Nevertheless, glibenclamide induced a significant decrease (p less than 0.005) in transglutaminase activity after 20 min of perfusion (629.83 +/- 53.08 and 521.18 +/- 43.92, mean +/- SE, at 0 and 20 min). No correlation was observed between glucose or insulin plasma levels and transglutaminase activity. PMID- 2894390 TI - Androgen producing adrenal adenoma. Report on a case associated with hyperparathyroidism. AB - In a 41-year-old hirsute woman, severe hypercalcemia led to the discovery of hyperparathyroidism related to the involvement (hyperplasia/or adenoma) of the 4 parathyroid glands. Plasma and urinary DHA, plasma DHA-sulfate and delta 5 steroid precursors were elevated. Steroid hormone hypersecretion was stimulated by hCG and ACTH, and exhibited a paradoxical rise during dexamethasone administration. Computerized tomography scanning as well as arteriography disclosed bilateral adrenal hyperplasia and left adrenal adenoma. Bilateral adrenal vein catheterization indicated a left/right gradient for delta 5 steroids and delta 5 steroid sulfates. At surgery a left brown adrenal encapsulated adenoma was removed with a hyperplastic adrenal gland. Results of in vitro studies (adrenal steroid content and incubation) together with postadrenalectomy hormonal results suggest that the left brown adrenal adenoma was the main source of excessive androgen production. The infrequent association of an androgen producing adrenal adenoma with hyperparathyroidism raises the hypothesis of multiple endocrine neoplasia syndrome. However, evidence for this diagnosis is lacking in the absence of other glandular involvement and of family history. PMID- 2894392 TI - Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production. AB - Studies of cell-surface molecules involved in human T cell interaction reveal that differential expression of each of three adhesion molecules (LFA-3, CD2, and LFA-1) subdivides human peripheral blood T cells into major subpopulations. Systematic analysis of the relationship between expression of these and other markers of T cell subsets demonstrates a single major subset of human peripheral blood T lymphocytes distinguished by enhanced expression of LFA-3, CD2, LFA-1, and three other markers (CDw29 [4B4], UCHL1, and Pgp-1). Large differences in relative expression are observed for UCHL1 (29-fold) and LFA-3 (greater than 8 fold), and smaller differences (2- to 4-fold) are seen for CDw29, CD2, LFA-1, and Pgp-1. Bimodal distribution of LFA-3 is found on both CD4+ cells and on CD8+ cells as well as on B lymphocytes (CD19+). Neonatal T cells (CD3+) are comprised almost exclusively of the subset expressing low LFA-3, CD2, LFA-1, CDw29, and UCHL1. Activation of cord peripheral blood mononuclear leukocytes with PHA leads to uniform enhanced expression of each of these molecules on CD3+ cells. Functional analyses of these T cell subsets were performed after sorting of adult T cells based on differential LFA-3 expression. Only the LFA-3+ subset proliferated in response to the Ag tetanus toxoid, even though the LFA-3- subset proliferated more strongly to PHA. Furthermore, the LFA-3+ subset made greater than fivefold more IFN-gamma than the LFA-3- subset in response to PHA, despite the fact that both subsets made equivalent amounts of IL-2. This phenotypic and functional analysis of resting and activated newborn and adult T cells indicates that human memory T cells express enhanced levels of LFA-3, CD2, LFA-1, UCHL1, CDw29, and Pgp-1; we speculate that the increase in expression of T cell adhesion molecules LFA-3, CD2, and LFA-1 on memory cells is functionally important in their enhanced responsiveness. PMID- 2894391 TI - Specific modulation by ethanol of the protein synthesis pattern in the C2 rat hepatoma cell line. AB - The effect of ethanol on protein synthesis in the C2 rat hepatoma cell line was analyzed by two-dimensional gel electrophoresis after the labeling with [35S]methionine of cells that were untreated or had been treated with 180 mM ethanol. In this cell line, this concentration of ethanol is known to induce gamma-glutamyl transpeptidase, a marker of alcoholism in man (Barouki et al., Hepatology 1983; 3: 323-329). In the present work we demonstrate that ethanol, besides causing a slight decrease in overall protein synthesis (less than 25%), primarily regulates the expression of two unique proteins among 1500 labeled products that were analyzed: one of these was induced and did not correspond to gamma-glutamyl transpeptidase, and one was repressed after 20 h of ethanol treatment. We conclude that the set of hepatic proteins altered by ethanol is likely to be very limited in number, which reflects the specificity of alcohol action on protein synthesis in the C2 cell line. PMID- 2894393 TI - Subpopulations of early thymocytes. A cross-correlation flow cytometric analysis of adult mouse Ly-2-L3T4-(CD8-CD4-) thymocytes using eight different surface markers. AB - Putative early thymocytes, the Ly-2-L3T4-(CD8-CD4-) cells representing 3 to 4% of adult CBA mouse thymic lymphocytes, were isolated in high purity (99.5%). They were then stained by using mAb and analyzed by flow cytometry for the expression of six additional surface antigenic markers. Cross-correlation of the data obtained from a complete series of successive two-parameter analyses revealed the existence of about 11 discrete subsets, falling into four-main groups, within the Ly-2-L3T4- population. All subsets consisted of relatively large lymphoid cells. The most numerous group of Ly-2-L3T4- cells was Ly-1 low B2A2-M1/69 high Thy-1 high Pgp-1 low and by these markers resembled Ly-2+L3T4+ cortical blasts. Many of the cells in this group were positive for the IL-2R and/or for MEL-14. A second major group of Ly-2-L3T4- cells was Ly-1 high B2A2-M1/69 low Pgp-1 high, and resembled in some respects activated mature T cells. This group had previously been shown to be absent from the embryonic thymus. The group could be divided into Thy-1 high and Thy-1 low subsets. None of the cells in this group were positive for the IL-2R and very few expressed MEL-14. A third group, 13% of the Ly-2-L3T4- population, was Ly-1 low B2A2-M1/69 low Pgp-1 high, and could also be divided into Thy-1 high and Thy-1 low subsets. A final minor group, 9% of the Ly 2-L3T4- population, was Ly-1 high B2A2-M1/69 high Pgp-1 low Thy-1 high. The particular pattern of markers on these subsets, combined with subsequent information on their properties, makes it unlikely that they all represent sequential steps in one continuous developmental stream, and indicates that complex developmental steps have occurred, even at this supposedly early stage of T cell differentiation. PMID- 2894394 TI - CD3-negative lymphokine-activated cytotoxic cells express the CD3 epsilon gene. AB - The expression of genes encoding different polypeptide chains of the TCR-CD3 complex was analyzed in a panel of cloned MHC-unrestricted cytotoxic cells. The clones were derived from CD3+ and CD3- human PBL. After expansion in rIL-2, all clones were able to lyse the NK-sensitive target cell line K562. In contrast, lysis of fresh tumor cells was achieved almost exclusively by CD3- clones. To test whether a known TCR-CD3 complex may be involved in MHC-unrestricted cytotoxicity, total RNA from nine CD3+ and 11 CD3- clones was isolated and hybridized with DNA probes for the TCR alpha-, beta-, and gamma-chains and for the CD3 gamma-, delta-, and epsilon-chains. TCR gamma transcripts were present at high levels in CD3+CD4- CD8- clones but were undetectable in all CD3- clones. Lysis of fresh tumor cells is an activity which can be independent of the TCR alpha beta and TCR gamma complexes because the CD3- clones did not express these TCR genes. Interestingly, all CD3- clones expressed CD3 epsilon transcripts, but not CD3 gamma- or delta-transcripts. CD3- lymphokine-activated cytotoxic cells may therefore be derived from immature T cells which do not yet express a complete CD3 complex. The CD3 epsilon chain, if expressed in CD3- cells in association with other molecules, could be involved in the activation and lytic function of these MHC-unrestricted cytotoxic cells. PMID- 2894395 TI - A T cell surface molecule different from CD2 is involved in spontaneous rosette formation with erythrocytes. AB - Increasing evidence indicates that rosettes which spontaneously from between human T cells and E might be of physiologic relevance. We show here that another T cell-surface molecule than CD2 is involved in rosette formation. Four mAb have been obtained reacting with human T cells that block rosettes with E from many species, including autologous cells. They react with a molecule, we termed E2, which is actively synthetized by T and monocytic cells. Immunoprecipitation revealed a major 32-kDa band. Immunoblots revealed a major 32-kDa band and a minor 20-kDa band. This molecule was detected on all T cells tested--and present at high densities on corticothymocytes, but at low densities on medullary thymocytes. It was also found on monocytes but not on B cells. However B-CLL cells did carry this molecule. E2 molecules were also detected on nonhematologic cells. Together with the recent evidence that 3 molecules from the erythrocyte surface are also involved for rosettes, intricate molecular interactions would account for adhesion of T cells to autologous E and possibly autologous nucleated cells. PMID- 2894396 TI - Lymphocyte-virus interactions. Identification of a restriction fragment permitting virus replication in lymphocytes. AB - We are interested in understanding the effects of virus infection on lymphocyte function. To approach this question, we used a unique system of two genetically related leporipoxviruses to generate recombinants. One of these viruses, malignant fibroma virus (MV), replicates in many different cell types, including lymphocytes. The other, Shope fibroma virus (SFV), replicates principally in fibroblasts, but cannot replicate in lymphocytes. Fibroblasts infected with SFV received restriction fragments from MV by transfection. Recombinant viruses were selected in vitro for their ability to replicate in lymphocytes. By these means we have identified one restriction fragment, the 10.8-kb BamHI "C" fragment, capable of transferring from MV to SFV the ability to replicate in lymphocytes. A family of recombinants bearing different sized inserts of this restriction fragment has been isolated and is being characterized. Lymphocytotropic recombinants bearing portions of this restriction fragment produce colony morphology in vitro intermediate between MV's plaques and SFV's foci. On the basis of their ability to grow in and suppress mitogen responsiveness of lymphocytes, these recombinants may be classified into four different groups. Group 1 viruses are the most immunosuppressive, whereas those of group 4 are least. These traits correlate with ability to replicate in lymphocytes. Genetic analysis of recombinants indicates that the most immunosuppressive recombinants do not necessarily contain the most fragment C DNA. Therefore, we have identified a restriction fragment, one or more of the genes of which are sufficient to allow an otherwise nonlymphocytotropic virus to replicate in lymphocytes. Additional genetic and immunologic analysis should permit us to determine the structure and function of the protein responsible for this effect. PMID- 2894397 TI - Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on murine skin. AB - The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on skin of congenic haired and hairless newborn and adult HRS/J mice was studied. In all adult animals topical application of TCDD caused an involution of sebaceous glands. Epidermal/epithelial hyperplasia and hyperkeratinization was induced in the hairless, but not the haired mice. Trans-glutaminase (TG) activity was stimulated in both haired and hairless animals. A single application of 1 microgram of TCDD did not stimulate significant ornithine decarboxylase activity in the skin in either strain. Other than a reduction in the density of the inflammatory cell infiltrate in the dermis, topical treatment with antiinflammatory agents fluocinolone acetonide and indomethacin did not affect the cutaneous response to TCDD. Skin of newborn mice treated topically with TCDD over a 2-wk period reacted much the same as adult skin in that sebaceous glands were reduced in size and TG activity was stimulated in both haired and hairless neonates; but epidermal hyperplasia occurred only in the hairless, not the haired newborns. PMID- 2894398 TI - Specific restriction fragment length polymorphism on the HLA-C region and susceptibility to psoriasis vulgaris. AB - In psoriasis vulgaris, the HLA class I Cw6 specificity has previously been recognized as the most commonly associated antigen serologically. This study was carried out to investigate whether or not the gene controlling the susceptibility to psoriasis vulgaris existed on the HLA, especially the HLA-C region. At first, we analyzed the restriction fragment length polymorphism (RFLP) of 13 patients with psoriasis vulgaris and 6 healthy controls who were all positive for at least one allele of HLA-Cw6. To characterize RFLP in psoriasis patients who did not have HLA-Cw6, 12 patients and 10 healthy controls who had HLA-Cw7 were also examined. Southern hybridization of genomic DNA demonstrated that DNA polymorphisms of the HLA-C antigen gene could not be found in any psoriasis vulgaris patient whether HLA-Cw6 or Cw7. However, a 4.5 kb BamHI fragment and a 3.1 kb PstI fragment were lacking in some healthy controls who had either HLA-Cw6 or Cw7. This study suggests that the presence of RFLP in the HLA-C gene is associated with psoriasis vulgaris. These specific fragments may help predispose individuals to psoriasis vulgaris, or may be essential for the development of the disease. PMID- 2894399 TI - Differences in reactogenicity and antigenicity of acellular and standard pertussis vaccines combined with diphtheria and tetanus in infants. AB - Clinical and serological responses of infants to primary immunization with diphtheria-tetanus-pertussis (DTP) vaccine containing components of acellular pertussis vaccine (DTP-AC) were compared in a double-blind study with responses of infants receiving whole-cell DTP vaccine (DTP-WC). Three doses of either DTP AC containing lymphocytosis-promoting factor (LPF) and filamentous hemagglutinin (FHA) or DTP-WC vaccine were given to infants at two, four, and six months of age. Nineteen infants received DTP-AC vaccine, and 20 infants received DTP-WC vaccine. Significantly more infants who received DTP-WC vaccine manifested fever, swelling, and/or total reactions than did infants who received DTP-AC vaccine. Infants who received DTP-AC vaccine had comparable antibody titers to LPF and significantly higher titers to FHA after three immunizations, as compared with the infants who received DTP-WC vaccine (P less than or equal to .001). The DTP WC vaccine stimulated higher pertussis agglutination titers (P = .04) than did DTP-AC. The DTP-AC vaccine was immunogenic and significantly less reactogenic in infants than was the currently used DTP-WC vaccine. PMID- 2894400 TI - Acute and acute-on-chronic mastoiditis (a five-year experience at Groote Schuur Hospital). AB - One hundred and thirty patients with acute-on-chronic mastoiditis were managed by the ENT Department of Groote Schuur Hospital between 1980 and 1984 inclusive. Seventy-four patients had cholesteatomas, of whom 78.4 per cent had intracranial extension and 44.6 per cent had intradural extension of the infection. In contrast, of the 56 patients without cholesteatomas, only 23.2 per cent had intracranial extension of the infection. These may be rare conditions in some privileged parts of the world but their lethal potential requires all ENT surgeons to be competent in their management. PMID- 2894401 TI - Otogenic intradural complications: (a review of 37 patients). PMID- 2894402 TI - Genetic analysis of autoimmune gld mice. I. Identification of a restriction fragment length polymorphism closely linked to the gld mutation within a conserved linkage group. AB - A linkage map of distal mouse chromosome 1 was generated using restriction fragment length polymorphism (RFLP) analysis of DNA prepared from 95 [C3H-gld/gld X Mus spretus)F1 X C3H-gld/gld] backcross mice. The gene order was: (centromere) C4bp, Ren-1,2, Ly-5, [At-3/gld], Apoa-2/Ly-17, Spna-1 (telomere). All mice expressing the phenotype of gld homozygotes were homozygous for the At-3 RFLP characteristic of C3H mice and none of the mice heterozygous for At-3 RFLPs had characteristics of gld homozygotes, demonstrating close linkage between these genes. The identification of an RFLP closely linked to the gld gene provides a starting point for the identification of a genetic defect that results in abnormal T cells and autoimmune disease. PMID- 2894403 TI - Comparison of two solid phase chemistry systems: Reflotron and Ektachem DT 60. AB - Solid phase chemistry can be used for clinical analysis at the bedside, and it is even applicable to whole blood. We compared precision, accuracy, method linearity, and practicability of two solid phase chemistry analysers. Reflotron (Boehringer Mannheim, W. Germany) and Ektachem DT 60 (Eastman Kodak Co, USA). Eight analytes, glucose, cholesterol, triacylglycerols, urea, uric acid, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase were investigated. The precision of both instruments was good. Coefficients of variation for within run and day to day precision were below 10% for all analytes. Methods were compared by analysing 88 to 105 patients sera for each investigated analyte on Reflotron, on Ektachem DT 60 and on a wet chemistry reference instrument. Linear regression analysis showed good agreement between wet chemistry and solid phase chemistry results. Coefficients of correlation (r) ranged from 0.957 to 0.999. Reflotron and Ektachem are desk top analysers. Reflotron is the smaller instrument. Currently, it offers 9 analytes and rapid single test performance. Whole blood can be used for all tests. Test strips can be stored at room temperature. Ektachem DT 60 has a modular design, and 22 analytes are available. Series of up to 100 tests per hour are possible. Whole blood can be used for the preparation of glucose and haemoglobin test slides. The slides must be deep frozen for prolonged storage. Reflotron may be suitable for the physician's office, Ektachem for small laboratories. The problem of quality control has not yet been satisfactorily solved for either instrument, as only analyser-specific control specimens can be used. Reagent costs of solid phase chemistry tests are high, especially when large test series are performed. Operation of both instruments requires well trained personnel. PMID- 2894404 TI - Effects of housing and muricidal behavior on serotonergic receptors and interactions with novel anxiolytic drugs. AB - Mouse killing by rats represents a predatory behavior that can be modified by drugs from several different therapeutic classes and by environmental conditions. Buspirone and gepirone, non-benzodiazepine anxiolytics that stimulate serotonergic receptors (5HT1a) and inhibit isolation-induced intraspecies aggression, were tested for inhibition of muricidal behavior by isolated rats. Neither buspirone (3.0 mg/kg s.c.) nor gepirone (from 5.0 to 40 mg/kg) inhibited muricide. Additional rats were housed, either aggregated or isolated, and tested for muricidal behavior 9 times over 5 weeks to establish which animals were muricidal: thus, there were 4 groups of rats: muricidal or non-muricidal under either isolated or aggregated housing condition. [3H]-Spiperone was used to determine striatal D2 receptor Bmax and Kd and prefrontal cortex D2 and 5HT2 receptor binding. There were no changes across the four groups. Binding of [3H]-5 hydroxytryptamine (5HT) to 5HT1a receptors decreased in septum of both groups of isolated rats and binding to 5HT1b receptors decreased 50% in hippocampus of isolated and aggregated muricidal rats. Binding of [3H]-5HT to either receptor was unchanged in amygdaloid area and hypothalamus across all groups. Thus, stimulating pre- and postsynaptic 5HT1a receptors does not alter muricidal behavior and changes in 5HT1 receptor binding occurs in limited areas. Whether this limited change in hippocampal 5HT1b binding is important for establishing muricidal behavior is unclear; however the direction of the change is consistent with reports that decreased serotonergic activity increases predatory behavior. PMID- 2894405 TI - Development of computer-assisted simulation procedure to analyze receptor modulatory processes. AB - Experimentally induced changes in neurotransmitter receptors have been analyzed by means of a computer assisted simulation procedure over a wide range of free ligand concentrations. This approach allows to evaluate, for a given range of ligand concentrations, the relative influence of simultaneous variations in binding parameters (i.e. dissociation constant or Kd and in maximal number of binding sites or Bm) and to predict the net and final effect of the experimental condition on the receptor-mediated transmission line. The function representing the changes in bound values versus the respective free ligand concentrations, has been studied analytically on the basis of all the possible values that the percent changes in both Kd and Bm parameters induced by a given experimental condition can assume. A well characterized change in the pattern of bound radioligand could in this way be defined. This approach, developed to show in an immediate and clear way treatment-induce changes in receptor populations or to fit directly rough experimental data expressed as differences in bound values versus free ligand concentrations, seems to be an useful complement to the widely used saturation analysis of binding data. PMID- 2894407 TI - Effects of systemic administration of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine to mice on tyrosine hydroxylase, L-3,4-dihydroxyphenylalanine decarboxylase, dopamine beta-hydroxylase, and monoamine oxidase activities in the striatum and hypothalamus. AB - The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg subcutaneously per day for 8 days) to C57BL/6N mice were studied on tyrosine hydroxylase (TH), L-3,4-dihydroxyphenylalanine decarboxylase (DDC), and monoamine oxidase (MAO) activities in the striatum, and TH, DDC, dopamine-beta-hydroxylase (DBH), and MAO activities in the hypothalamus. Treatment with MPTP led to a large decrease in TH activity and a parallel decrease in DDC activity in the striatum, as compared with the saline controls. In contrast, MPTP administration did not cause a decrease of the activities of TH, DDC, and DBH in the hypothalamus. There was also no reduction in MAO activities of striatum and hypothalamus. These data indicate that MPTP administration to mice results in specific degeneration of the dopaminergic nigrostriatal pathway and that DDC in the mouse striatum may mainly be localized in the dopaminergic neurons with TH. PMID- 2894406 TI - Irreversible binding and recovery of the norepinephrine uptake system using an alkylating derivative of norepinephrine. AB - The effects of bromoacetylaminomenthylnorepinephrine (BAAN) on the sodium dependent, high-affinity norepinephrine (NE) uptake system in rat brain synaptosomes and CNS neuronal cultures were investigated. BAAN inhibited [3H]NE uptake into synaptosomes in a dose- and time-dependent manner (IC50, 6.5 microM). Pretreatment of cortical synaptosomes or neuronal cells with BAAN alone, followed by washing to remove free drug, reduced the Vmax but did not alter the Km value for [3H]NE uptake. The BAAN-induced reduction in Vmax was attenuated by concurrent pretreatment with desipramine and blocked by the reaction of BAAN with dithiothreitol or cysteine. In contrast, BAAN was 19-fold less potent at inhibiting [3H]dopamine uptake in striatal synaptosomes, and no change in the Vmax or Km value for [3H]dopamine uptake was observed after a pretreatment with BAAN followed by washing. Furthermore, the irreversible beta-antagonist, bromoacetylalprenololmentane, was equipotent to BAAN for inhibiting [3H]NE uptake into cortical synaptosomes, but did not alter the Vmax or Km for [3H]NE after pretreatment. In neuronal cultures, BAAN inhibited sodium-dependent uptake of [3H]NE (IC50, 5.6 microM) with no effect on sodium-independent uptake. After pretreatment of cultures with 30 microM BAAN followed by washing, there was a 74% decrease in the Vmax for [3H]NE uptake. Following a 24-h lag period, uptake recovered to the control level within 48 h; however, recovery was completely blocked by cycloheximide. The data indicate that BAAN irreversibly binds to the [3H]NE uptake system in both CNS synaptosomes and neuronal cultures and may be a useful probe for studying the turnover of the [3H]NE uptake system. PMID- 2894408 TI - Increases in striatal and hippocampal impedance and extracellular levels of amino acids by cardiac arrest in freely moving rats. AB - The time course of changes in the tissue impedance and the levels of extracellular transmitter and non-transmitter amino acids was studied in the striatum and hippocampus of the unanesthetized rat after cardiac arrest. Electrodes were implanted for the continuous measurement of tissue impedance so that a measure of the volume of extracellular space was provided. Alternatively, bilateral dialysis probes were used for monitoring levels of extracellular amino acids in subsequent 30-s samples using an automated precolumn derivatization technique for reversed-phase HPLC analysis and fluorimetric detection. The impedance started to rise approximately 1.2 min following cardiac arrest, increased rapidly during the first 5 min, and increased almost linearly thereafter. After 15 min, a decrease of approximately 50% in the extracellular space was calculated. The impedance rose more steeply in the striatum than in the hippocampus. The extracellular levels of taurine, which increased greater than 300% within 5 min after cardiac arrest, most closely resembled the time course of the change in impedance. Glutamate and aspartate levels did not increase until 5 min after circulatory arrest, and at 15 min they had risen to a level of 465 and 265% for the striatum and 298 and 140% for the hippocampus of the resting release, respectively. The release of gamma-aminobutyric acid (GABA) was multiphasic and did not resemble that of any of the other--putative--transmitter amino acids. Fifteen minutes after cardiac arrest, the levels of GABA were 617 and 774% of the resting release in the striatum and hippocampus, respectively. Glycine and alanine efflux substantially increased (232 and 151% in striatum and 141 and 154% in hippocampus, respectively) 15 min postmortem, whereas the glutamine level was slightly increased and levels of asparagine, histidine, threonine, ethanolamine, serine, arginine, and tyrosine were inconsistently higher in the two brain regions. At this time, the extracellular levels of glutamate, GABA, and aspartate were only slightly lower, as expected from the tissue levels and from levels of the other amino acids, an observation indicating that all the amino acids may diffuse through postmortem brain tissue to a nearly similar extent.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2894409 TI - Specificity and reversibility of the inhibition by HgCl2 of glutamate transport in astrocyte cultures. AB - Inhibition of glutamate transport is a potential indirect cause of excitotoxic damage by glutamate in the CNS. The mercuric ion, the form in which metallic mercury vapor is believed to exert its neurotoxic action, is a known inhibitor of amino acid transport. This study examines the specificity with which HgCl2 inhibits glutamate transport in mouse cerebral astrocytes by means of comparative measurements of 2-deoxyglucose uptake. Uptake of 2-deoxyglucose is an index of glucose utilization that reflects the function of Na+,K+-ATPase and hexokinase, and is sensitive to Na+ entry. The kinetic parameters, ionic dependence, and substrate specificity of glutamate transport in these astrocyte cultures were consistent with the commonly occurring system designated X-AG. Acute exposure to 0.5 microM HgCl2 inhibited by 50% the initial rate of glutamate transport but did not affect 2-deoxyglucose uptake. Glutamate transport was not detectably inhibited by Al2+, Pb2+, Co2+, Sr2+, Cd2+, or Zn2+ (10 microM as chlorides). The inhibitory action of 0.5 microM HgCl2 on glutamate transport was rapidly reversible. The action of 1-2 microM HgCl2 was progressive when exposures were extended to 1-3 h, and was more slowly reversible. These results suggest that Hg2+ can impair glial glutamate transport reversibly at exposure levels that do not compromise some other vital cell functions. PMID- 2894410 TI - Regulation of transmitter gamma-aminobutyric acid (GABA) synthesis and metabolism illustrated by the effect of gamma-vinyl GABA and hypoglycemia. AB - The effect of different treatments on amino acid levels in neostriatum was studied to throw some light on the synthesis and metabolism of gamma-aminobutyric acid (GABA). Irreversible inhibition of GABA transaminase by microinjection of gamma-vinyl GABA (GVG) led to a decrease in aspartate, glutamate, and glutamine levels and an increase in the GABA level, such that the nitrogen pool remained constant. The results indicate that a large part of brain glutamine is derived from GABA. Hypoglycemia led to an increase in the aspartate level and a decrease in glutamate, glutamine, and GABA levels. The total amino acid pool was decreased compared with amino acid levels in normoglycemic rats. GVG treatment of hypoglycemic rats led to a decrease in the aspartate level and a further reduction in glutamate and glutamine levels. In this case, GABA accumulation continued, although the glutamine pool was almost depleted. The GABA level increased postmortem, but there were no detectable changes in levels of the other amino acids. Pretreatment of the rats with hypoglycemia reduced both glutamate and glutamine levels with a subsequent decreased postmortem GABA accumulation. The half-maximal GABA synthesis rate was obtained when the glutamate level was reduced by 50% and the glutamine level was reduced by 80%. PMID- 2894412 TI - Occurrence of a large Ca2+-independent release of glutamate during anoxia in isolated nerve terminals (synaptosomes). AB - Isolated rat cerebral cortical synaptosomes made anoxic by addition of cyanide developed an inhibition of the Ca2+-dependent release of glutamate 2 min after the addition of the metabolic inhibitor when the intrasynaptosomal ATP/ADP ratio decreased below 1.7. In contrast, cyanide induced a continuous efflux of glutamate through a Ca2+-independent pathway that accounted for the release of 25% of total intrasynaptosomal glutamate in 5 min. The results suggest that a Ca2+-independent release of glutamate could be implicated in the neurotoxic action of this amino acid during anoxia. PMID- 2894411 TI - Noncholinergic transmitter(s) maintains secretion of catecholamines from rat adrenal medulla for several hours of continuous stimulation of splanchnic neurons. AB - The effect of continuous stimulation of splanchnic nerves at 1, 3, and 10 Hz on the secretion of catecholamines from the isolated rat adrenal gland was examined. Secretion evoked at 10 Hz declined over 60% in 1 h, and by the end of 4 h the secretion was only 10% of the initial value. The secretion evoked at 3 Hz was unchanged in the first hour, but showed a gradual decline in subsequent hours. In contrast, secretion evoked at 1 Hz was well maintained for several hours. Even after 6 h of continuous stimulation, the decline was only about 35%. Atropine plus hexamethonium reduced the secretion evoked at 10 Hz by over 80%, but that evoked at 1 Hz was reduced by about 35%; addition of naloxone reduced it to 75%. When the secretion declined to very low levels after continuous stimulation at 10 Hz for 100 min, a change in frequency to 3 Hz or 1 Hz caused a sharp rebound in the secretory response. Returning the frequency back to 10 Hz led to a sharp drop in the secretion, whereas reducing the frequency to 1 or 3 Hz once again increased the secretion. The rebound in the secretory response after switchover of frequencies was observed in the presence of atropine plus hexamethonium, but was abolished by naloxone. Extensive stimulations, which caused large amounts of catecholamine secretions at each frequency, were not associated with any loss in tissue catecholamine contents. The major conclusion is that secretion of catecholamines is maintained uninterrupted for several hours when splanchnic nerves are stimulated at low frequency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894413 TI - Differentiation and maturation of embryonal carcinoma-derived neurons in cell culture. AB - We have previously shown that retinoic acid-treated cultures of the P19 line of embryonal carcinoma cells differentiate into neurons, glia, and fibroblast-like cells (Jones-Villeneuve et al., 1982). We report here that the monoclonal antibody HNK-1 reacts with the neurons at a very early stage of their differentiation and is, therefore, an early marker of the neuronal lineage. Cells in differentiated P 19 cultures synthesized acetylcholine but not catecholamines, suggesting that at least some of the neurons are cholinergic. The neurons also carry high-affinity uptake sites for GABA but not for serotonin. In long-term cultures, neuronal processes differentiated into axons and dendrites, which formed synapses. This biological system should prove valuable for examining the development and maturation of cholinergic neurons, since their differentiation occurs in cell culture. PMID- 2894414 TI - High-affinity uptake of noradrenaline in quail dorsal root ganglion cells that express tyrosine hydroxylase immunoreactivity in vitro. AB - During embryonic life, avian sensory ganglia contain cells with the potential to express, under appropriate experimental conditions, a number of properties characteristic of autonomic sympathetic neurons. Thus, cells capable of synthesizing noradrenaline (NA) from tyrosine differentiate when dorsal root ganglia (DRG) from 10-15 d embryonic quail are grown in culture (Xue et al., 1985a, b). In the present study, we show that cultures of DRG from 10 d embryos can take up 3H-NA by a high-affinity (Km = 1.0 microM), temperature-dependent process that can be inhibited by desmethylimipramine. By means of combined immunocytochemistry and autoradiography, it was demonstrated that the majority (70-80%) of the tyrosine hydroxylase (TH)-immunoreactive cells that developed in the cultures possessed a transport system for NA. Catecholamine (CA) uptake also occurred in a small, but relatively constant, number of TH-negative cells, but was absent from substance P-containing neurons. In contrast to TH, which appears only after 3-4 d in vitro, cells capable of taking up NA with high affinity were found in DRG cultures after only a few hours, and a small number (less than 0.5% of the total cell population) was detected in freshly removed, uncultured ganglia. Such cells did not react with antibodies directed against substance P or neurofilament proteins. We conclude that autonomic precursors are identifiable in a subset of non-neuronal DRG cells, prior to full expression of a noradrenergic phenotype, by their possession of a high-affinity uptake system for CA. PMID- 2894416 TI - Effect of methotrexate on perfusion and nitrogen-13 glutamate uptake in the Walker-256 carcinosarcoma. AB - The tissue uptake of [13N]glutamate (glu) was related to that of [11C]butanol (but), a highly diffusible perfusion tracer. In 25 rats bearing Walker-256 carcinomas tumor-to-muscle glu uptake averaged 6.34 +/- 2.84 (s.d.) prior to interventions and the respective uptake of but was 6.79 +/- 3.08 (y = 0.03 + 0.94x). One hour after selective intraarterial administration of methotrexate (mtx), glu uptake fell by 47%, whereas blood flow remained within the pretreatment range (N = 9). Four hours after mtx, perfusion was reduced by approximately 40%, and 2 days later both perfusion and glu uptake reached extremely low levels. No significant difference in the effect of 10 and 50 mg/kg mtx was observed. Regional tissue mtx uptake estimations using 77Br-labeled bromomethotrexate did not reveal any significant uptake in muscle. The relationship between tumor-to-muscle uptake of glu and but (13N/11C-index) was 0.94 +/- 0.015 (s.e.m., N = 25) before intervention. After methotrexate (1 hr, 4 hr, and 2 days) this index was 0.58 +/- 0.06 (N = 9), and 0.85 +/- 0.04 (N = 11) and 1.03 +/- 0.05 (N = 5), respectively. These values demonstrate an early mtx induced uncoupling of glu uptake with respect to perfusion. PMID- 2894417 TI - In vivo binding in rat brain and radiopharmaceutical preparation of radioiodinated HEAT, an alpha-1 adrenoceptor ligand. AB - In vivo binding of [125I]-2-[beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl tetralone) ([125I]HEAT) to alpha-1 adrenoceptors in the rat brain was determined over 4 hr. Uptake in the thalamus and frontal cortex was approximately 0.1% injected dose per gram tissue. Thalamus/cerebellum ratios of 10:1 and frontal cortex/cerebellum ratios of 5:1 were found at 4 hr. Pretreatment with prazosin, an alpha-1 antagonist, completely inhibited the accumulation of [125I]HEAT in thalamus and frontal cortex; yet uptake of radioactivity was not significantly affected by antagonists and agonists for other receptors classes (propranolol, beta-1; apomorphine, D-1; spiperone, D-2). Binding of [125I]HEAT is saturable. At 4 hr, [125I]HEAT or [123I]HEAT was shown to be the only radioactive material in rat thalamus and frontal cortex. Iodine-123 HEAT and [125I]HEAT were synthesized as radiopharmaceuticals within 3 hr in 99% radiochemical purity. PMID- 2894415 TI - Heterogeneity of GABAergic cells in cat visual cortex. AB - Antibodies against neuropeptides and against a vitamin D-dependent calcium binding protein (CaBP) label small cells with nonpyramidal-like morphology in the cat visual cortex (areas 17, 18, and 19). Since GABAergic cells are interneurons, a double-staining procedure was used to test for the coexistence of cholecystokinin (CCK), somatostatin (SRIF), neuropeptide Y (NPY), corticotropin releasing factor (CRF), vasoactive intestinal polypeptide (VIP), and CaBP with glutamic acid decarboxylase (GAD). Our results show that CRF and VIP do not coexist with GAD, while the 3 other peptides and CaBP do. Hence GAD-positive cells can be subdivided into 4 broad groups: (1) cells that are only GAD positive, (2) cells that are GAD- and CaBP-positive, (3) GAD-positive neurons also containing CCK, and (4) GAD-positive cells that also contain SRIF. A small subset of class 2 also contains SRIF and most cells of class 4 also contain NPY. The 4 classes of GAD-positive cells differ in laminar position: class 1 predominates in layers IV and V, classes 2 and 3 in the upper laminae (II and III), and class 4 in the deepest layer (VI). PMID- 2894418 TI - Dihydropyridines and beta-adrenoceptor antagonists as combination treatment in hypertension. AB - The combination of one of the dihydropyridine class of calcium channel antagonists with a beta-adrenoceptor blocker has particular therapeutic advantages in the management of hypertension. The beta-blocker reduces the effects of the dihydropyridine-induced reflex increases in sympathetic nervous system and renin-angiotensin system activity, while the dihydropyridine reduces the peripheral effects of beta-blockade. Numerous studies have documented additional antihypertensive effects when these two classes of agents are used as combination therapy in hypertension. This therapeutic combination is well tolerated and produces minimal alterations in clinical laboratory tests. Initial concerns that the combination may impair atrioventricular conduction and left ventricular function have not been substantiated in widespread clinical trials. PMID- 2894421 TI - Care of the patient with an epidural catheter: an infection control challenge. PMID- 2894419 TI - Effects of calcium channel antagonists and other antihypertensive drugs on atherogenesis. AB - This paper reviews published data concerning the effects of antihypertensive drugs on the development of atherosclerosis in experimental animal models with hyperlipoproteinaemia. Emphasis is placed on the influence of calcium channel antagonists on this process, and the potential mechanisms responsible for the effect. In addition, studies of the action of beta-receptor antagonists on atherogenesis are also summarized. The results indicate that several antihypertensive drugs may inhibit or retard experimentally-induced atherogenesis, even in normotensive animals, although the mechanisms for the effects remain poorly understood. PMID- 2894420 TI - Regression of structural alterations of hypertension with calcium antagonists- vascular hypertrophy. AB - Structural vascular changes in the precapillary arterioles are a cardinal feature of established hypertension, and have been described in several vascular beds. In brief, the wall:lumen ratio becomes increased due to hypertrophy of the vascular smooth muscle cells. This results in a reduction of the inner radius in the precapillary vessels, which causes a structurally based vascular hyperreactivity and accentuates the increase in systemic vascular resistance, another hallmark of established hypertension. Much interest has been devoted to the possibility of obtaining a regression of these structural vascular changes. Previously, the emphasis was on obtaining a fall in blood pressure, but more recently additional factors have also been considered, in particular the so-called trophic factors. In this context the calcium antagonists of the dihydropyridine type appear to be of particular interest, since these are markedly effective in lowering elevated arterial pressure, while at the same time they do not cause reflex-mediated elevations of trophic factors during long-term treatment. Few clinical data are yet available to show whether calcium antagonists can cause a regression of structural vascular changes, but some recent animal work suggests that they are clearly useful in this respect. PMID- 2894422 TI - [Changes in auditory brainstem responses in rats, following experimental manipulation of noradrenergic activities]. PMID- 2894423 TI - Postnatal development of the innervation and paraganglia in the porcine pulmonary arterial bed. AB - The innervation of the pulmonary trunk and pulmonary arterial bed was studied in 17 pigs from birth to 6 months of age. After birth, the pulmonary trunk and extra and intra-pulmonary arteries contained neurofilament and protein gene-product immunoreactive nerve fibres in both the adventitia and media. The density of nerve fibres increased from birth to 2 months, this being most marked during the first 2 weeks of life. Most of the fibres in the media were presumed to be sympathetic in origin as they contained both neuropeptide tyrosine and tyrosine hydroxylase immunoreactivity. Fibres were associated with the vasa-vasorum and vascular smooth muscle running around the vessel, between the elastic laminae and smooth muscle cells, in the outer two-thirds of the media. Vasoactive intestinal polypeptide and calcitonin gene-related peptide-immunoreactive nerve fibres were found to be associated with the pulmonary trunk and extra-pulmonary artery, but generally not with the intra-pulmonary arteries. Tyrosine hydroxylase immunoreactivity was detected in the glomus cells at birth, but peptide immunoreactivity (enkephalin) was not demonstrated in paraganglia until 14 days of age. Adaptation to extra-uterine life is associated with rapid development changes in the innervation of the pig pulmonary trunk, extra- and intra-pulmonary arteries and in the expression of peptide immunoreactivity in both nerve fibres and glomus cells. These changes may have a role in the postnatal adaptation of the pulmonary circulation. PMID- 2894424 TI - Somatostatin secretion in cultured human islet cells from patients with nesidioblastosis: a compensatory mechanism? AB - Two patients with nesidioblastosis, one with persistent hypoglycemia and another who was asymptomatic, underwent pancreatic resection. Dispersed pancreatic islets were prepared from each patient. Insulin secretion from cultured islet cells was increased and somatostatin decreased in the symptomatic patient compared with the asymptomatic patient. Immunocytochemistry showed increased somatostatin containing cells in the asymptomatic patient. We hypothesize that this may be the mechanism by which some patients with nesidioblastosis maintain normal serum glucose levels. PMID- 2894425 TI - Biochemical and pharmacological tests for the prediction of ability of monoamine uptake blockers to inhibit the uptake of noradrenaline in-vivo: the effects of desipramine, maprotiline, femoxetine and citalopram. AB - The ability of desipramine and maprotiline (NA uptake inhibitors), as well as citalopram and femoxetine (5-HT uptake inhibitors) to protect mice against brain NA depletion induced by H 77/77 (4-alpha-dimethyl-m-tyramine), has been compared with their ability to counteract reserpine (2.5 mg kg-1)- or apomorphine (16 mg kg-1)-induced hypothermia and to potentiate TRH (40 mg kg-1)-induced hyperthermia in mice. While both NA uptake inhibitors antagonized the action of H 77/77, maprotiline being weaker than desipramine, femoxetine and citalopram were inactive. However, in contrast to citalopram, femoxetine was active in the other tests, being about twice as weak as maprotiline, which itself was several times weaker than desipramine in those tests. On the basis of the results obtained it is concluded that functional in-vivo tests for NA uptake inhibitors are more sensitive than the H 77/77 biochemical test; moreover, femoxetine, which in-vitro studies is less selective than citalopram, may inhibit the uptake of NA in-vivo. PMID- 2894426 TI - Adenosine reduces agonist-induced production of inositol phosphates in rat aorta. AB - In rat aortic strips rendered permeable with digitonin, inositol trisphosphate induced an efflux of 45Ca from the tissue. This release was not affected by adenosine. In tissues not treated with digitonin the contents of inositol trisphosphate (IP3) and its metabolite inositol 1-phosphate (IP1) were significantly enhanced by noradrenaline in the lithium-treated rat aorta. Adenosine was without effect on levels of IP1 or IP3 in tissues which had not been pretreated with noradrenaline, however, the noradrenaline-enhanced tissue content of IP1 was reduced by adenosine in a dose-dependent manner. The reduction in IP1 content by adenosine was enhanced by the uptake blocker dipyridamole (10 microM) and was blocked by the adenosine receptor antagonist 8-phenyltheophylline (10 microM). Adenosine may therefore lower production of inositol phosphates and thus reduce the stimulated release of calcium from intracellular stores. It is proposed that a reduction in phosphatidylinositol turnover may play a role in adenosine-mediated relaxation of blood vessels. PMID- 2894427 TI - Investigation into the effects in-vitro of the 5-hydroxytryptamine reuptake inhibitor, alaproclate, on carbachol-stimulated inositol phospholipid breakdown in the rat cerebral cortex. AB - The effect of alaproclate in carbachol-stimulated inositol phospholipid (PI) breakdown in rat cerebral cortical miniprisms has been investigated. Carbachol stimulated PI breakdown was greatly enhanced by increasing the assay potassium concentration from 5.88 to 18.2 mM. Alaproclate, on the other hand, did not influence carbachol-stimulated PI breakdown over the concentration range tested (0-100 microM) at either assay [K+]. The elution pattern of the inositol phosphates from the Dowex-1 columns was also unaffected by alaproclate both in the absence and presence of carbachol. Thus, the potentiation by alaproclate of tremor and salivation induced by the muscarinic agonist oxotremorine in-vivo reported previously is not seen when muscarinic function is measured in-vitro using carbachol-stimulated PI breakdown. PMID- 2894429 TI - Lymphoid tissue responses to a novel perfluorochemical emulsion in rats. AB - The effects of a novel perfluorochemical emulsion on rat lymphoid tissues and antibody production against sheep red blood cells (SRBC) have been studied. The responses were compared with those following injection of identical doses of the proprietary emulsion, Fluosol-DA 20% (F-DA). Liver weight was increased up to 15% at 8 days following intravenous (i.v.) or intraperitoneal (i.p.) injection of the novel emulsion but was unaffected by F-DA injection. Spleen weight also increased by a maximum of 20% in response to i.p. injection of the novel emulsion but this was less than increases of up to 44% which occurred in F-DA-injected rats. Thymus weight decreased (P less than 0.05) following i.p. injection of the novel emulsion whereas mesenteric lymph node (MLN) weight remained unchanged. However, MLN weight was increased in response to i.v. injected F-DA, while thymus weight showed a small increase following i.p. F-DA injection. Mean plasma antibody titres to SRBC were significantly (P less than 0.01) increased at 7 days after immunization in rats pretreated with i.p. injections of either the novel emulsion or F-DA; titres in animals pretreated with i.v. injections of either emulsion were similar to control. PMID- 2894428 TI - Muscarinic receptor density is reduced in diabetic rat atria, an effect prevented by the aldose reductase inhibitor, Statil. AB - Binding assays using [3H]quinuclidinyl benzilate (QNB) as a muscarinic receptor ligand were carried out on atrial tissue from 6 control and 11 six-week streptozocin-diabetic rats. Five of the latter had received the aldose reductase inhibitor, Statil (25 mg kg-1 day-1 orally). Dissociation constants for specific (atropine displaceable QNB) binding were not changed either by diabetes or Statil treatment. Muscarinic receptor numbers, as estimated by Bmax values, were, however, significantly depressed in tissues from the untreated diabetic group, compared with tissues from either the controls or the Statil-treated diabetic group. These results may explain the reduced sensitivity to muscarinic agonists previously observed in atria from similarly diabetic rats and indicate the involvement of the sorbitol pathway in the change. Possible mechanisms are discussed. PMID- 2894430 TI - The effects of bromhexine hydrochloride and S-carboxymethyl-L-cysteine on guinea pig uterine microflora. AB - This study used guinea-pigs as a mammalian model to investigate the effects of bromhexine hydrochloride and S-carboxymethyl-L-cysteine on the integrity of the cervical mucus plug. It was shown that under normal circumstances the uterus is sterile, but following drug administration microorganisms began to appear in the uterus with no significant effect on the vaginal microbial population. It therefore appears that these two mucolytic agents may reduce cervical mucus viscoelasticity. After the animals had been mated, microorganisms were isolated from the uterus even in the absence of drug treatment. PMID- 2894431 TI - Proglumide, a cholecystokinin receptor antagonist, exacerbates alloxan-induced diabetes mellitus in Swiss mice. AB - The effect of proglumide ((+/-)-4-benzamido-N,N-dipropyl-glutaramic acid), a gastrin and cholecystokinin receptor antagonist, has been studied on the fasting plasma glucose (FPG) and insulin levels in normal and alloxan-diabetic mice. In normal mice, proglumide, administered as a single oral dose or twice daily for five consecutive days, did not produce any alteration in those parameters. Injection of alloxan monohydrate (70 mg kg-1 i.v.) produced a significant decrease in plasma insulin and a significant elevation of FPG levels on the 5th day after its administration as evidence of diabetes mellitus. Proglumide sodium, given as a single acute dose on the 5th day of alloxan injection, or as a twice daily dose for 5 days immediately after alloxan injection, significantly exacerbated the hyperglycaemia and further decreased the plasma insulin levels thus worsening the diabetogenic effect of alloxan. These observations point to a possible involvement of cholecystokinin (CCK) in alloxan-induced diabetes and indicate a need for monitoring the levels of FPG in diabetic patients being treated with a high dose of proglumide or other CCK-antagonists. PMID- 2894432 TI - Effect of vanadate on cooling-induced tension changes in K-depolarized smooth muscles from guinea-pigs. AB - Sodium vanadate reversed cooling-induced relaxation of K-depolarized taenia coli of guinea-pigs but failed to reverse it in the portal vein and uterus. It potentiated cooling-induced contraction of K-depolarized vas deferens and ureter. These effects were not mediated by the inhibition of Na,K-ATPase, but by the inhibition of the Ca-pump. PMID- 2894433 TI - Diazepam facilitates reflex bradycardia in conscious rats. AB - The effects of diazepam on cardiovascular function were assessed in conscious rats. Intravenous administration of diazepam (1-30 mg kg-1) produced a dose dependent decrease in both the mean arterial pressure and the heart rate. Also, reflex bradycardia was produced in rats by intravenous infusion of adrenaline (1.25-2.5 micrograms kg-1). Intravenous pretreatment of the rats with diazepam, although causing no change in the adrenaline-induced pressor effect, did enhance the adrenaline-induced reflex bradycardia. However, the diazepam enhancement of adrenaline-induced reflex bradycardia was antagonized by pretreatment of rats with an intravenous dose of picrotoxin (an agent blocks chloride channels by binding to sites associated with the benzodiazepine-GABA-chloride channel macromolecular complex). The data indicate that diazepam acts through the benzodiazepine-GABA-chloride channel macromolecular complex within the central nervous system to facilitate reflex bradycardia mediated through baroreceptor reflexes in response to an acute increase in arterial pressure. PMID- 2894434 TI - The calcium channel antagonist, verapamil, potentiates the inhibitory action of morphine on intestinal and biliary motility. AB - The effects of morphine and verapamil have been assessed on the gastrointestinal propulsion of charcoal meal and egg yolk-induced gall bladder emptying in mice. Each drug significantly inhibited these functions. In combination, an additive effect was seen on the inhibition of gastrointestinal transit, whilst verapamil potentiated the morphine-induced inhibition of gall bladder emptying. It is concluded that calcium ion channel antagonists may potentiate the activity of opiate drugs. PMID- 2894436 TI - Surface area and crystallinity of Form A of chloramphenicol palmitic and stearic esters: which one is the limiting factor in the enzymatic hydrolysis? AB - Chloramphenicol stearic and palmitic esters in the polymorphic Form A, when ground for 85 h showed an in-vitro enzymatic hydrolysis rate constant (Khydr), the value of which was the same as that of a commercial Form B. The increase in the rate of the enzymatic hydrolysis was not related to the specific surface area as shown by the fact that the micronized Form A, having a higher specific surface area value than ground Form A, showed the same Khydr as the unground Form A. The Khydr value of the ground Form A could be the result of an increase in the crystalline disorder brought about by the grinding process. PMID- 2894435 TI - Nitrates do not affect prostacyclin formation by rat arteries: this is unrelated to increased vascular prostacyclin formation with age. AB - The question of whether vasodilator nitrates act by releasing prostacyclin is controversial. Since the ability of blood vessels to form prostacyclin changes with age, we have investigated whether this may explain the discrepancies in the literature. It does not, since isosorbide dinitrate or glyceryl trinitrate incubated with rat aorta or vena cava from male Wistar rats had little or no effect on the release of prostacyclin, measured as 6-keto-PGF1 alpha. We confirm that the aorta produces substantially more prostacyclin than the vena cava. The arterial production of prostacyclin was greater in rats weighing 350-400 g than in those weighing 116-152 g, but the production by the veins was similar in both groups. PMID- 2894439 TI - High capacity for pulmonary first-pass elimination of propranolol in rats. AB - Plasma propranolol concentrations after i.v. and i.a. 1, 2.5, 5 and 10 mg kg-1 doses of the drug given intravenously or intra-arterially have been compared in 7 week-old male Wistar rats. The areas under the curves after i.a. dosing were almost twice those after i.v. dosing at any dose, despite the elimination half lives being the same. The difference in total body clearance after i.a. dosing from that after i.v. dosing indicated a significant contribution by pulmonary clearance, which ranged from about 20 to 30 mL min-1 kg-1, to the overall first pass elimination after the i.v. administration. The pulmonary extraction ratio was approximately 0.4 to 0.5 at the i.v. doses used. Mean pulmonary transit time was estimated to be about 1 to 2 min. There was no dose-dependence in the pulmonary first-pass elimination kinetics of propranolol. PMID- 2894438 TI - An alteration in the liver microsomal membrane of the rat following paracetamol overdose. AB - Fluorescence polarization of dansyl chloride covalently labelled microsomal membranes revealed an alteration in rat liver microsomal membranes following as a consequence of a paracetamol overdose. This suggests that dansyl chloride would be a useful probe in the study of the effects of paracetamol on microsomal membranes. PMID- 2894437 TI - Spectrophotometric study of the photodecomposition kinetics of nifedipine. AB - Nifedipine is a photosensitive compound. Irradiation for 4 h under a fluorescent lamp placed 30 cm from a solution of nifedipine in 95% ethanol leads to complete photo-oxidation as determined spectrophotometrically. The disappearance of the reduced form and appearance of the oxidized form is best described by zero-order kinetics at concentrations higher than 4 x 10(-4) M. At lower concentrations pseudo-first order kinetics are followed. Monochromatic irradiation of nifedipine at wavelengths 400 to 700 nm in 25 nm increments showed no change in the absorbance at 280 nm, and, except for a hyperchromic effect at 237 nm, no other spectral changes were observed. Its photo-oxidation was dependent on the intensity of light and increased exponentially as solutions were irradiated progressively closer to a fluorescent light source. The pH studies showed that aqueous solutions of nifedipine photo-oxidized fastest at pH 2. PMID- 2894440 TI - Guanethidine N-oxidation in human liver microsomes. AB - The capacity of human liver microsomes to N-oxidize guanethidine from 25 subjects has been assessed. Guanethidine N-oxidation was optimal at pH 8.5 and proceeded at only 16% of the maximal rate at pH 7.4. The mean rates of guanethidine N oxidation at pH 8.5 and 7.4 were 2.46 +/- 0.89 (mean +/- s.d., n = 25) and 0.38 +/- 0.22 (mean +/- s.d., n = 22), respectively. Interindividual differences in the rate of guanethidine N-oxidation at pH 8.5 and 7.4 were 17- and 11-fold, respectively. The cytochrome P450 inhibitors, proadifen and 2,4-dichloro-6 phenylphenoxyethylamine (DPEA), at both pH 8.5 and 7.4 caused less than 20% reduction in the rate of guanethidine N-oxidation by human liver microsomes. These data indicate that guanethidine N-oxidation can be used as a measure of flavin-containing monooxygenase activity in human liver. PMID- 2894442 TI - The characterization of the mechanical properties of microcrystalline cellulose: a fracture mechanics approach. AB - The mechanical properties of compressed beam specimens of microcrystalline cellulose (Avicel pH 101) have been assessed in terms of the tensile strength (sigma t), Young's modulus (E) and the following fracture mechanics parameters: the critical stress intensity factor (KIC), the critical strain energy release rate (GIC) and the fracture toughness (R). Increase in the compaction pressure used to form the beams resulted in compacts with higher values of tensile strength, Young's modulus, KIC, GIC and R, indicating that the compacts became less brittle as their porosity decreased. Extrapolation of the values of sigma t, E, KIC, GIC and R to provide values at zero porosity indicated that the material had values of 30 Nm m-2, 0.0103 GPa, 1.21 MN m-3/2, 1.98 x 10(2) Nm-1 and 2.19 x 10(3) Nm-1, respectively. These provide a range of values whereby a fuller characterization of the mechanical properties of pharmaceutical materials can be made. PMID- 2894441 TI - Tomoxetine and the stereoselectivity of drug action. PMID- 2894443 TI - The twin impinger: a simple device for assessing the delivery of drugs from metered dose pressurized aerosol inhalers. AB - The development is described of the twin impinger, a two-stage separation device for assessing the drug delivery from metered dose inhalers and other oral inhalation delivery devices. The discharged aerosol is fractionated by firing through a simulated oropharynx and then through an impinger stage of defined aerodynamic particle size cut-off characteristics. The fine (pulmonary) fraction which penetrates is collected by a lower impinger. It is demonstrated that this device is able to assess individually the fine particle delivery of both components of two-drug aerosols. Formulations showing undue agglomeration or serious crystal growth of drug are readily detected. The twin impinger is shown to be a valuable device for routine quality assessment of aerosols during product development, stability testing and for quality assurance and comparison of commercial products. PMID- 2894444 TI - Monolayer studies on poly(isobutylcyanoacrylate)-ampicillin association. AB - Surface pressure-area isotherms (pi-A) of poly(isobutylcyanoacrylate) monolayers with or without glucose and dextran as polymerization adjuvants used in the preparation of nanoparticles have been derived from measurements made at the air water interface with the subphase pH at 2.7, 5.5 or 8.8. The isotherms were characteristic of the expanded type of polymer monolayer curves, yielding unusually low limiting area values compared with those of other known poly(acrylate) derivatives. This behaviour may be explained by the folding of polar moieties of the polymer groups in the water subphase. Ampicillin incorporated during preparation of nanoparticles had a negligible effect on the general behaviour of adjuvant-free monolayers, but a significant one on the adjuvant-loaded polymer monolayer system which showed an increase in surface area throughout the compression cycle, as compared with the surface area of the adjuvant-free polymer system although the collapse pressure was practically the same at 67 mN m-1. PMID- 2894445 TI - Comparison of albumin and casein microspheres as a carrier for doxorubicin. AB - Doxorubicin (Adriamycin)-loaded casein and albumin microspheres, with diameters between 14 and 38 micron (50% weight average) were prepared by glutaraldehyde stabilization of the aqueous phase (containing protein and drug) of a water in oil emulsion. Physical properties, drug loading characteristics and release rates from microspheres in-vitro have been compared and correlated with effects on tumour growth when injected intratumourally in rats. Compared with albumin, the surface charge of the casein system was more negative and the microspheres exhibited a slower release of drug in-vitro. Both observations could be explained by the lower drug content of the casein system. There was evidence for the formation of a doxorubicin complex in the microspheres, the significance of which is not yet known. Casein microspheres containing 11 micrograms of doxorubicin had a similar inhibitory effect on tumour growth (growth delay = 20.7 days) to 85 micrograms of drug incorporated into albumin microspheres (growth delay = 18.6 days). The absence of a simple dose-response relationship shows that carrier matrix can influence potency of incorporated drug. The results are consistent with release rate of the drug from microspheres (obversely, rate of drug delivery to the tumour), being a determinant of potency in these systems. PMID- 2894446 TI - The stereoselectivity of the 'single drug binding site' of human alpha 1-acid glycoprotein (orosomucoid). AB - The stereoselective binding of six pairs of basic, one pair of acidic drug enantiomers, and one pair of diastereomers for human alpha 1-acid glycoprotein was investigated by means of competition experiments against [3H]propranolol- or [14C]nicardipine-labelled binding sites using equilibrium dialysis to separate free from bound marker ligand. The affinity constants (Ka) for association of [3H]propranolol and [14C]nicardipine with alpha 1-AGP were 1.2 +/- 0.6 X 10(5) M 1 and 3.4 +/- 1.4 X 10(5) M-1, respectively, and control binding amounted to 57 +/- 7 and 91 +/- 2%, respectively. The following selectivity factors, calculated as the ratio of the higher over the lower enantiomer concentrations displacing 15% of control radiomarker binding (IC15-value), were obtained against propranolol and nicardipine: (-)/(+) propranolol: 1.9 and 1.7.; (+)-/(-) disopyramide: 2.8 and 1.4; (+)-/(-)-verapamil: 1.6 and 1.9; (+)-(S)-/(-)-(R)-202 791, a dihydropyridine derivative: 2.6 and 2.0; (-)-/(+)-asocainol: 1.7 and 3.0; (+)-/(-)-tilidine: 1.1 and approximately equal to 2; (-)-(S)-/(+)-(R)- warfarin: 1.6 and 2.4; (+/-)-cis/(+/-)-trans-trans-tilidine: 1.7 and 1.8. When the calculation of radioligand-free fractions is also taken into account, it is apparent that only the tilidine isomers show no selectivity at propranolol marked, and the disopyramide isomers at nicardipine-marked alpha 1-AGP-binding sites, in all other cases, a weak selectivity is detectable, which is, however, far below the values obtained for most neurotransmitter receptors. It is concluded that the single drug binding site of alpha 1-AGP is only slightly stereoselective and that the stereoselective binding of the drugs investigated is probably of no clinical consequence. PMID- 2894447 TI - Influence of cardiopulmonary resuscitation on plasma concentrations of nimodipine in the dog. AB - The influence of cardiopulmonary resuscitation on the plasma concentrations of nimodipine in the anaesthetized dog has been examined. Nimodipine was given as a bolus injection followed by a maintenance infusion. When, during the maintenance infusion, the dogs were subjected to cardiac arrest followed by external cardiac massage combined with artificial ventilation (basic life support), a fast and almost threefold increase in the steady-state plasma concentrations of nimodipine was observed. When the maintenance infusion of nimodipine was stopped immediately before cardiac arrest and basic life support, the nimodipine concentrations decreased. These results indicate that during basic life support, there is a decreased transfer of infused nimodipine from plasma to the tissues. This is also supported by the fact that for antipyrine, a drug with a smaller volume of distribution than nimodipine, the increase in plasma concentrations when infused during cardiac arrest and basic life support, was much smaller. When nimodipine was started after restoration of the spontaneous circulation (advanced life support) in dogs that had been subjected to cardiac arrest and basic life support, the plasma concentrations were not significantly higher than in control dogs. It can be concluded that the fate of nimodipine is markedly altered during basic life support but not in the period following restoration of spontaneous circulation. PMID- 2894448 TI - Effect of inflammation and proadifen on the disposition of antipyrine, lignocaine and propranolol in rat isolated perfused liver. AB - The effect of inflammation, induced in rats by injection of turpentine oil, on drug disposition has been evaluated in rat isolated perfused livers. The drugs studied were a low extraction drug, antipyrine, and two high extraction drugs, lignocaine and propranolol. Turpentine significantly increased the half-life of antipyrine and of propranolol, but not that of lignocaine. Proadifen (SKF 525A) significantly increased the half-life of all three drugs. Turpentine decreased the clearance of antipyrine significantly by about 50% and that of propranolol non-significantly by about 20%, but did not affect the clearance of lignocaine. Proadifen significantly decreased the clearance of all three drugs, but this was most pronounced for antipyrine. In both turpentine- and proadifen-treated rats a significant increase in volume of distribution of propranolol was observed. The results show that, as with proadifen, turpentine-induced inflammation affects the hepatic clearance of antipyrine in the rat isolated perfused liver. With both high extraction drugs, the effect of inflammation on their clearance was low or absent, in contrast to the effect of proadifen. This suggests that a possible effect of inflammation on intrinsic clearance is not large enough to influence the hepatic clearance of the high extraction drugs. PMID- 2894449 TI - [The behavior of 1,4-benzodiazepine drugs in acidic media. IX. Effect of hydrolyzate of flutazolam on the central nervous system]. PMID- 2894450 TI - Liquid chromatographic determination of 9-methyl-3-(1H-tetrazol-5-yl)-4H pyrido[1,2-a]pyrimidin-4-one in human plasma with fluorescence detection. AB - A simple and sensitive assay for quantitating 9-methyl-3-(1H-tetrazol-5-yl)-4H pyrido[1,2-a]pyrimidin-4-one (1; BMY 26517) in human plasma was developed using high-performance liquid chromatography with fluorescence detection. The method involves precipitation of protein and reversed-phase chromatography. The method is linear in the range of 4.3-429 ng/mL of 1, and the limit of detection is 0.4 ng/mL. The day-to-day precision values of this method at 25.7 and 386 ng/mL are 2.1 and 2.6%, respectively. The day-to-day accuracy values at these concentrations are 99.7 and 99.8%, respectively. The recovery of 1 is 98.3%. PMID- 2894451 TI - Drug interactions between imipramine and benzodiazepines in rats. AB - The concomitant administration of diazepam and imipramine hydrochloride increased desipramine concentration in rat plasma, but decreased 2-hydroxyimipramine and 2 hydroxydesipramine concentrations; the concomitant administration of oxazepam and imipramine hydrochloride decreased imipramine, 2-hydroxyimipramine, and 2 hydroxydesipramine concentrations. Imipramine plasma protein binding was unaltered in all cases. Liver concentrations of imipramine and 2 hydroxydesipramine were increased by concomitant administration of oxazepam and imipramine hydrochloride. Concomitant administration of benzodiazepines and imipramine hydrochloride increased imipramine concentration in the brain. The effects of imipramine hydrochloride on hypothermia induced by reserpine, and on behavioral despair in rats was also studied. The concomitant administration of diazepam and imipramine hydrochloride led to a decrease in the anti-reserpine effect of imipramine hydrochloride and in the imipramine hydrochloride-induced recovery from immobility in the forced swimming test. These results are in accord with the findings on brain concentrations of imipramine and its metabolites. PMID- 2894452 TI - Determination of temazepam and related compounds in capsules by high-performance liquid chromatography. AB - A reversed-phase, high-performance liquid chromatographic assay method is described for temazepam hard gelatin and soft gelatin capsule analysis. The method is simple, specific, accurate, fast, and stability indicating. A reversed phase octylsilane (C8) column with a mobile phase composed of methanol:1% acetic acid and detection at 254 nm separated sulfanilamide (internal standard), temazepam, synthetic precursor, and possible degradation products. Detector responses showed linearity to temazepam concentrations over the range 0.075-0.60 mg/mL (r = 0.9999). Mean recovery of temazepam added to capsule excipients was 100.3%. Mean assay results for 15- and 30-mg hard gelatin capsules were 101.5 and 101.3%, respectively. Mean assay results for 10- and 20-mg soft elastic gelatin capsules were 101.1 and 101.5%, respectively. PMID- 2894453 TI - Inhibition of vasopressin-stimulated cyclic AMP accumulation by alpha-2 adrenoceptor agonists in isolated papillary collecting ducts. AB - The effects of selective alpha adrenoceptor agonists and antagonists on vasopressin (VP)-sensitive cyclic AMP (cAMP) formation in microdissected rat papillary collecting ducts were examined. In the presence of 10(-10) M VP, norepinephrine and the selective alpha-2 adrenoceptor agonist, B-HT 933, produced almost total inhibition of VP-stimulated cAMP accumulation. Half-maximal inhibition occurred at 1 x 10(-8) M and 6 x 10(-7) M for norepinephrine and B-HT 933, respectively. Cirazoline, a selective alpha-1 adrenoceptor agonist, had no significant effect on VP-stimulated cAMP accumulation. The inhibitory effects of norepinephrine and B-HT 933 were antagonized by rauwolscine but not by prazosin. The antagonism of B-HT 933-induced inhibition of VP-stimulated cAMP accumulation was competitive with an antagonist dissociation constant (KB) of 10.9 x 10(-9) M. Preincubation of papillary collecting ducts with pertussis toxin (1 microgram/ml for 1 hr at 37 degrees C) attenuated, by 65%, the inhibitory effect of B-HT 933 on VP-stimulated cAMP levels. These results demonstrate that alpha-2 adrenoceptors capable of inhibiting VP action are present on the papillary collecting duct. Furthermore, the alpha-2 adrenoceptor-induced inhibition of VP stimulated cAMP accumulation is pertussis-toxin sensitive. This suggests that alpha-2 adrenoceptors are coupled negatively to adenylate cyclase, via the guanine nucleotide binding protein, in the collecting tubule. PMID- 2894454 TI - Opioid receptor-mediated responses in the dentate gyrus and CA1 region of the rat hippocampus. AB - We compared the effects of selective opioid compounds on the excitability of dentate granule cells and CA1 pyramidal cells in the rat hippocampal slice. Synaptic excitability was assessed by measuring the effects of opioids on stimulus-response relationships and on the generation of afterpotentials as detected by extracellular recording. Opioids increased the excitability of both dentate granule and CA1 pyramidal cells in a naloxone-reversible manner. In the dentate gyrus, opioids changed the stimulus-response curve of the primary evoked response from a biphasic to a sigmoid shape and, in CA1, opioids shifted the sigmoid stimulus-response curve to the left without altering the maximal amplitude of the response. Multiple population spikes were evoked by orthodromic stimulation in the presence, but not the absence, of opioid agonists in both regions. Analysis of relative agonist potencies and antagonist sensitivities revealed mu, delta and kappa receptors in the dentate gyrus, but only mu and delta receptors in CA1. Mu-selective agonists had greater maximal effects than delta- or kappa-selective agonists in both regions. The effects of opioids on dentate granule cell excitability were similar to those of the gamma-aminobutyric acid antagonists bicuculline and pentylenetetrazole, thus opioids appear to act via a disinhibitory mechanism in the dentate gyrus as has been proposed in CA1. Our results suggest that endogenous opioid peptides may act by inhibiting interneurons, thereby disinhibiting dentate granule cells. PMID- 2894455 TI - Characterization of alpha-2 adrenergic receptors in the OK cell, an opossum kidney cell line. AB - We have characterized alpha-2 adrenergic receptors in OK cells, an opossum kidney derived cell line. In membrane saturation binding experiments, [3H]rauwolscine (Kd = 74 pM) was 3-fold more potent than [3H]yohimbine (Kd = 230 pM). Each labeled a single class of binding sites with densities of 135 and 124 fmol/mg of protein for [3H]rauwolscine and [3H]yohimbine, respectively. Inhibition of [3H]rauwolscine and [3H]yohimbine binding by several alpha adrenergic agonists and antagonists demonstrated the radioligands labeled an alpha-2 type adrenergic receptor with a pharmacological profile similar to the alpha-2B receptor subtype. The rank order of potency for antagonist inhibition of binding was yohimbine greater than prazosin = phentolamine greater than chlorpromazine = corynanthine, whereas the rank order of agonist potency was oxymetazoline = clonidine greater than or equal to UK-14,304 greater than or equal to (-)-epinephrine greater than (-)-norepinephrine. The oxymetazoline, clonidine and antagonist inhibition curves were routinely monophasic and modeled best as a single class of binding sites. For the other agonists, inhibition binding curves were biphasic with approximately 35% of the binding sites existing in a high affinity state. These curves were shifted to the right in the presence of 0.1 mM GTP, and in general modeled as a single class of binding sites. UK-14,304, (-)-epinephrine, (-) norepinephrine and oxymetazoline attenuated parathyroid hormone-stimulated cyclic AMP production by up to 70% in whole cell monolayers in a dose-dependent manner via a pertussis toxin-sensitive mechanism. With the exception of oxymetazoline, this inhibition could be reversed with alpha adrenergic antagonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894456 TI - Differential effect of aluminum on the blood-brain barrier transport of peptides, technetium and albumin. AB - Aluminum is a neurotoxin capable of altering membrane structure and function. We investigated whether aluminum also can affect saturable transport across membranes using the blood-brain barrier as our model. Mice were given i.p. or i.v. aluminum (up to 100 mg/kg) as the chloride salt and the disappearance from the brain of several centrally administered substances was measured. We found that aluminum rapidly and profoundly inhibited the saturable system that transports the small, N-tyrosinated peptides Tyr-MIF-1 and the enkephalins from the brain to the blood by acting as a noncompetitive inhibitor. In contrast, the disappearance from the brain of technetium pertechnetate (a substance also transported out of the brain by a different saturable system), albumin or D-Tyr MIF-1 (a stereoisomer of Tyr-MIF-1 that was confirmed not to be transported by the carrier system) was not affected by aluminum. Aluminum also did not alter either the saturable or nonsaturable component of the uptake of Tyr-MIF-1 by erythrocytes. These findings suggest that one mechanism by which aluminum may induce neurotoxicity is by selective alteration of the transport systems of the blood-brain barrier. PMID- 2894457 TI - Distinct bradykinin receptors mediate stimulation of prostaglandin synthesis by endothelial cells and fibroblasts. AB - Bradykinin-stimulated prostaglandin synthesis was investigated in Swiss albino 3T3 fibroblasts (Swiss 3T3 cells) and bovine pulmonary artery endothelial cells (CPAE). Previous studies have indicated that bradykinin stimulates arachidonic acid release in Swiss 3T3 cells by activating phospholipase A2 and by activating phosphatidylcholine-specific phospholipase C in CPAE cells. The dose-response for bradykinin-stimulated prostaglandin synthesis was similar in Swiss 3T3 cells and CPAE cells. Marked differences were found in the effects of several bradykinin analogs in Swiss 3T3 cells and CPAE cells. des-Arg9-bradykinin was a partial agonist in CPAE cells whereas it was completely inactive in Swiss 3T3 cells. [p chloro-D-Phe6-D-Pro7]-Bradykinin was a full agonist in Swiss 3T3 cells, but only a partial agonist, exhibiting a bell-shaped curve, in CPAE cells. The bradykinin antagonist, [D-Arg0-Hyp3-D-Phe7]-bradykinin, was a several-fold more potent antagonist in Swiss 3T3 cells, compared to CPAE cells. The effects of these bradykinin analogs on prostaglandin synthesis do not fit the previously described BK1, BK2 bradykinin receptor classification. These findings suggest that there are at least two bradykinin receptors which stimulate prostaglandin synthesis. Previous studies have indicated that these two bradykinin receptors may be coupled to different transduction pathways for the release of arachidonate. PMID- 2894458 TI - Effects of selective 5-hydroxytryptamine-2 and nonselective 5-hydroxytryptamine antagonists on the differential-reinforcement-of-low-rate 72-second schedule. AB - The effects of antidepressant drugs, administered with and without a 5 hydroxytryptamine (5-HT) antagonist that is not selective for 5-HT receptor subtypes, were assessed in rats responding under a differential-reinforcement-of low-rate 72-second (DRL 72-s) schedule of reinforcement. The increases in reinforcement rate seen after low dose tricyclic antidepressant drug administration were antagonized by the 5-HT antagonist methysergide. Methysergide did not antagonize either the increases in reinforcement rate or the decreases in response rate induced by the atypical antidepressant trazodone or the putative antidepressant clenbuterol. In addition, the effects of 5-HT receptor antagonists with varying selectivity for the 5-HT2 relative to the 5-HT1 receptor subtypes were assessed when administered alone. The rank order potency series for the maximal increase in the reinforcement rate after administration of the 5-HT antagonists was ketanserin greater than pipamperone greater than trazodone greater than cyproheptadine greater than cinanserin greater than metergoline greater than methysergide, in close agreement with the selectivity of these drugs for the 5-HT2 relative to the 5-HT1 receptor subtypes. In addition, the specificity of the DRL 72-s schedule was further assessed with the alpha adrenergic antagonists phentolamine and phenoxybenzamine which both decreased the response rate but did not increase the reinforcement rate as do antidepressant drugs. These results suggest that the therapeutic effect of atypical antidepressants such as trazodone and mianserin may be related to selective antagonism of 5-HT2 receptors. Furthermore, agonist action at a 5-HT1 receptor and antagonist action at 5-HT2 receptors both appear to contribute to antidepressant-like activity on the DRL 72-s schedule. PMID- 2894459 TI - Molecular genetics of catecholamines as an approach to the biochemistry of manic depression. AB - Manic depressive illness has been clearly established to exhibit a strong genetic component and is therefore amenable to linkage analysis using random DNA markers. In view of the catecholamine hypothesis of this disorder, the gene encoding tyrosine hydroxylase (TH) the limiting enzyme in catecholamines is a good candidate to investigate. This gene has been localized to chromosome 11 in close linkage with Harvey-ras-1. The various transcriptional and post-transcriptional mechanisms that modulate short and long-term TH activity are discussed. Human tyrosine hydroxylase is coded by at least three distinct mRNAs derived from a single gene. This variation has clear functional consequences and could represent a novel mode of regulating catecholamines levels in normal and pathological neurons. PMID- 2894460 TI - Search for a gene that predisposes individuals to BPI disorder. AB - To determine the role of genetics in bipolar affective disorders it was necessary to have correct diagnoses and large homogenous population(s). To identify a marker linked to the disease two additional factors were important, a correct model for genetic transmission and highly polymorphic DNA markers. With the establishment of a linked marker the aim is to identify the susceptibility gene. Two approaches are the prediction of candidate genes and/or the determination of a physical map of the region. PMID- 2894461 TI - Searching for a major genetic locus for affective disorder in the Old Order Amish. PMID- 2894462 TI - Neuropeptide gene polymorphisms in affective disorder and schizophrenia. AB - The restriction fragment length polymorphisms (RFLPs) associated with neuropeptide Y (NPY) and somatostatin loci were used to assess the possibility of linkage to a locus for affective disorder (AD). When somatostatin haplotypes were assigned to members of 2 AD pedigrees under either rare dominant or recessive transmission, the LOD scores obtained at 0% recombination were inconsistent with linkage. Similar results were obtained with NPY under rare dominant inheritance. Comparison of the frequency of the genotypes deduced from the polymorphic alleles of gastrin-releasing peptide, NPY, somatostatin and substance P in normals vs patients with either AD or schizophrenia suggests the absence of association. The difference in the frequency of the 3.3 kb adenosine deaminase fragment in normals vs bipolar and schizophrenic patients is of borderline significance. PMID- 2894464 TI - Protein polymorphisms detected by two-dimensional electrophoresis: an analysis of overall informativeness of a panel of linkage markers. AB - Forty-two independent polymorphic loci are detectable by two-dimensional electrophoresis (2DE) of four peripherally accessible human tissues. Fifteen have been chromosomally mapped and, taken together, these constitute a useful panel of markers for genetic linkage studies in humans. An analysis of the overall informativeness for linkage of this panel of markers is presented, taking into account the effect of varying the number of families or matings studies. Use of 2DE polymorphic markers for linkage of genetically determined behaviour traits in humans and mice is reviewed. PMID- 2894463 TI - Minisatellite mapping in manic depression. AB - Hypervariable regions of DNA exist at many discrete loci in the human genome. Variations in the length of specific classes of hypervariable DNA termed "minisatellite" sequences may be detected by hybridisation of radioactive probes composed of a common 10-15 base pair repeat or "core" sequence which is shared by each of the minisatellite loci. Such a procedure was used to perform linkage analysis on a kindred in which a disease allele causing manic depression appeared to be segregating as an autosomal dominant. Results indicate no apparent linkage between a manic depression allele and at least 20 hypervariable genetic loci which acted as markers. However, because of the hypervariability of the minisatellite loci these results do not preclude similar analyses of other manic depressive pedigrees being productive because each such family will have distinct observable minisatellite alleles at loci specific to that family. The method could be usefully applied to the genetic analysis of other psychiatric disorders where heterogeneity is suspected and where a single autosomal major gene locus appears to be responsible for causing multiple cases within a single kindred. PMID- 2894465 TI - 2,4-Diamino-6,7-dimethoxyquinazolines. 4. 2-[4-(substituted oxyethoxy) piperidino] derivatives as alpha 1-adrenoceptor antagonists and antihypertensive agents. AB - A series of 4-amino-6,7-dimethoxy-2-[4-(substituted oxyethoxy)piperidino] quinazoline derivatives (2) was synthesized and evaluated for alpha-adrenoceptor affinity and antihypertensive activity. Most compounds showed binding affinities within the nanomolar range for alpha 1-receptors, although 25 and 26 showed enhanced potency (Ki, ca. 1.5 X 10(-10) M), equivalent to that of prazosin. Series 2 also displaced [3H]clonidine from alpha 2-adrenoceptors, but at relatively high doses of 10(-6) M, and selectivity for alpha 1 sites still predominated. In a rabbit pulmonary artery preparation, 12, 16, and 25 were potent antagonists of the alpha 1-mediated, postjunctional vasoconstrictor activity of norepinephrine with no effect at the prejunctional alpha 2 sites which modulate transmitter release. Physicochemical measurements gave a pKa of 7.63 +/- 0.10 for 12, and N-1 protonation will be favored (60%) at physiological pH to provide the alpha 1-adrenoceptor pharmacophore, 28. Antihypertensive activity of series 2 was evaluated following oral administration to spontaneously hypertensive rats, and blood pressure was measured after 1 and 6 h. Compounds 12, 13, 16, 23, and 37 displayed moderate efficacy and duration of action in lowering blood pressure, but the plasma half-life (ca. 2 h) of 16 in dogs was not compatible with potential once-daily administration in humans. PMID- 2894466 TI - Atypical antipsychotic agents: patterns of activity in a series of 3-substituted 2-pyridinyl-1-piperazine derivatives. AB - A series of 3-substituted 2-pyridinyl-1-piperazine derivatives have been appended to cyclic imide groups and evaluated for their potential antipsychotic activity. The dopamine receptor affinities of these target molecules, as well as their ability to block apomorphine-induced stereotypy or reverse neuroleptic-induced catalepsy, was dependent on the lipophilic and electronic characteristics of the substituent situated on the pyridine ring. Groups with + omega and - phi values were most consistent with the desired biological profile of the target molecules, the cyano moiety being the optimum choice. Evaluation of compound 12 in a monkey model of amphetamine psychosis, and the regional selectivity it expresses for the A10 dopaminergic cell bodies in electrophysiological experiments, suggest this compound would be an atypical antipsychotic agent with few side effects. PMID- 2894467 TI - Development of a new physicochemical model for brain penetration and its application to the design of centrally acting H2 receptor histamine antagonists. AB - A rational approach to the design of centrally acting agents is presented, based initially upon a comparison of the physicochemical properties of three typical histamine H2 receptor antagonists which do not readily cross the blood-brain barrier with those of the three brain-penetrating drugs clonidine (6), mepyramine (7) and imipramine (8). A good correlation was found between the logarithms of the equilibrium brain/blood concentration ratios in the rat and the partition parameter, delta log P, defined as log P (1-octanol/water)-log P (cyclohexane/water), which suggests that brain penetration might be improved by reducing overall hydrogen-bonding ability. This model has been employed as a guide in the design of novel brain-penetrating H2 antagonists by the systematic structural modification of representatives of different structural types of H2 antagonists. Although marked increases in brain penetration amongst congeners of cimetidine (1), ranitidine (9), and tiotidine (10) were achieved, no compound was found with an acceptable combination of H2 antagonist activity (-log KB in the guinea pig atrium greater than 7.0) and brain penetration (steady-state brain/blood concentration ratio greater than 1.0). Conversely, structural modification of N-[[(piperidinyl-methyl)phenoxy]propy]acetamide (30) led to several potent, novel compounds which readily cross the blood-brain barrier. One of these, zolantidine (SK&F 95282, 41), whose -log KB is 7.46 and steady-state brain/blood ratio is 1.4, has been identified for use in studying histaminergic H2 receptor mechanisms in brain. Comparison of delta log P values with the logarithms of the brain/blood ratios for 20 structurally diverse compounds for which data became available confirms a highly significant correlation and supports the general validity of this model. PMID- 2894468 TI - Confirmation of prenatal diagnosis of cystic fibrosis by DNA typing of fetal tissues. AB - Tissues from eight fetuses, diagnosed on the basis of amniotic fluid microvillar enzyme assay as having cystic fibrosis, were conserved in frozen storage for up to three years. Adequate samples of undegraded DNA could be extracted from small intestine, lung, and liver. DNA typing, with restriction fragment length polymorphisms tightly linked to the cystic fibrosis gene, showed all eight diagnoses to have been correct. Determining the DNA genotype of fetal material can also be used to establish the linkage relationship between markers and the cystic fibrosis gene, and will permit subsequent first trimester prenatal diagnosis for couples who have no living affected child. PMID- 2894469 TI - Slight hyperinsulinaemia but no hypoglycaemia in pertussis patients. AB - Because of the central role postulated for Pertussis Toxin in the pathogenesis of whooping cough, and the well-established ability of this toxin to alter insulin and glucose levels in animal blood, a study of insulin and glucose levels in hospitalised pertussis patients and in controls was made. With blood specimens collected in heparin-fluoride anticoagulant, the geometric mean plasma-insulin level (13.3 microU/ml) in a series of 24 pertussis patients was slightly, but statistically significantly, higher than that (8.9 microU/ml) in a series of 27 non-pertussis controls with other infectious diseases (p less than 0.02). Portions of the same blood specimens collected in lithium-heparin anticoagulant yielded higher mean plasma-insulin values of 15.5 and 11.4 microU/ml respectively, with no significant difference between them (p less than 0.05). Mean plasma glucose concentrations were not significantly different between the two groups, and hypoglycaemia was not detected in any pertussis patient. There were no statistically significant differences between pertussis and control children in the mean levels of plasma calcium, magnesium or phosphate. PMID- 2894470 TI - Adult respiratory distress syndrome (ARDS): the pathophysiologic role of catecholamine-kinin interactions. AB - The pathophysiology of the adult respiratory distress syndrome (ARDS) seems to be based on a cybernetic imbalance of the central nervous system (CNS), with activation of secondary peripheral effectors (PE). Lung vascular hyperpermeability is a crucial feature of PE actions in ARDS. Kinins (Bk), as PE, are important vascular hyperpermeability-inducing factors, with potential participation in ARDS induction. To test this hypothesis, we produced experimental ARDS in male Wistar rats using the anterior hypothalamic nuclei lesion model. Adrenalectomy, adrenal demedullation and denervation, alpha adrenergic blockade, and catecholamine (CA) depletion reduced ARDS severity whereas beta-adrenergic blocking and CA uptake I inhibition resulted in a potentiated aspect. The Bk depletion or inhibition of the generation of these peptides resulted in attenuation of the pathologic features of ARDS. Bk half-life prolongation produced intense potentiation of the respiratory syndrome. This work suggests that Bk and CA systems are interactive and interdependent in their pathogenic actions on lungs in ARDS, involving, probably, a reciprocally activating mechanism. PMID- 2894471 TI - Pulmonary consequences of severe tricyclic antidepressant ingestion. AB - We prospectively studied 56 consecutive patients with severe tricyclic antidepressant ingestion to determine the incidence of associated pulmonary complications. Among the patients meeting the entrance criteria, the mean antidepressant level was 1136 ng/ml. Other characteristics were a QRS duration of greater than or equal to 0.1 seconds in 35 (63%) and seizures in 19 (34%). Seventeen patients (30%) developed 18 abnormal chest X-ray findings which included pulmonary edema in 8 cases and aspiration pneumonia in 10. Using logistic regression, we evaluated the influence of tricyclic antidepressant level, blood pressure, QRS interval, seizures, drug co-ingestion and the use of gastric lavage vs. ipecac-induced emesis on pulmonary complications. For patients with pulmonary edema, the only significantly associated factor was hypotension on emergency department presentation. For aspiration pneumonia, no significant associations were found. Co-ingestion of another drug had no apparent influence on the development of pulmonary abnormalities. Our findings suggest that pulmonary edema and aspiration pneumonia are frequent complications of severe ingestions of tricyclic antidepressants. Pulmonary edema appears to result from hypotension or its treatment. The etiology of aspiration pneumonia is unclear. A chest X-ray should be obtained in all victims of tricyclic antidepressant overdose. PMID- 2894472 TI - The effect of fluid volume on syrup of ipecac emesis time. AB - Large volumes of fluid have been recommended to aid rapid ipecac-induced emesis, however, large volume intake may also have deleterious effects. We prospectively studied 121 children treated at home by a regional poison center to determine if a relationship existed between fluid volume and time to emesis. These children were treated in the usual manner except that parents were asked to measure the volume of fluid given and to note the time that fluid was given and the time of first emesis. The time ranged from 6 to 58 minutes (mean 20.6) with two who failed to respond and the volume ranged from 0 to 28 ounces (mean 6.7 ounces). In children who respond to ipecac, there is no significant relationship between the amount of fluid given and the time until emesis. We conclude that the traditional recommendation of forcing fluid with syrup of ipecac does not hasten emesis in children. PMID- 2894475 TI - N-acetylaspartylglutamate. A neuropeptide in the human visual system. PMID- 2894473 TI - A viable mutation in cauliflower mosaic virus, a retroviruslike plant virus, separates its capsid protein and polymerase genes. AB - A viable strain of cauliflower mosaic virus is described which arose by illegitimate recombination of two lethal parents. In this strain, the normally overlapping open reading frames IV and V, corresponding to the retrovirus gag and pol genes, are separated by a short intergenic region, suggesting that in this virus and in contrast to retroviruses, fusion of gag and pol gene products is not obligatory. PMID- 2894474 TI - Analysis of adenovirus type 2 L1 RNA 3'-end formation in vivo and in vitro. AB - Downstream sequence requirements for efficient cleavage and polyadenylation at the adenovirus type 2 L1 poly(A) site were determined in vivo in 293 cells and in vitro by using RNA precursors in HeLa cell nuclear extracts. The two cleavage sites used were found to differ in sensitivity to 3'-end deletion in vivo and in vitro. PMID- 2894476 TI - [Contact dermatitis due to befunolol hydrochloride eyedrops]. PMID- 2894477 TI - [The quantitative analysis for healing process of peptic ulcer by using Markov process]. PMID- 2894478 TI - [Effect of somatostatin on bile acid metabolism]. PMID- 2894479 TI - Emergency treatment of injured teeth. PMID- 2894480 TI - Molecular sorting during endocytosis. PMID- 2894481 TI - Tumor regression of an ileal carcinoid under the treatment with the somatostatin analogue SMS 201-995. AB - A 53-year-old man with metastatic ileal carcinoid ultimately failed to respond to conventional measures of surgery and was finally treated with a new long acting somatostatin analogue, SMS 201-995 for 7 months. SMS 201-995 not only gave symptomatic relief but also induced a reduction in metastatic tumor mass. PMID- 2894482 TI - Low prevalence of antibody to adult T-cell leukemia-associated antigen (anti ATLA) in hospital personnel. PMID- 2894483 TI - Ketoconazole inhibition and glucocorticoid action in the human lymphoblastic leukemia cell line CEM-C7. AB - The antifungal drug, ketoconazole, was reported to antagonize the induction of the enzyme tyrosine aminotransferase (TAT) by glucocorticoids in hepatoma tissue culture (HTC) cells, and to compete with glucocorticoids for binding to the glucocorticoid receptor. Since glucocorticoids inhibit the growth of the human leukemia cell line CEM-C7, ketoconazole might be expected to reverse this inhibition. Unexpectedly, ketoconazole inhibited CEM-C7 cell growth without utilizing glucocorticoid receptors. This was confirmed by ketoconazole inhibition of the growth of a receptor-less subline of CEM-C7 cells which are insensitive to glucocorticoids. Ketoconazole competed with triamcinolone acetonide (TA) for binding to the glucocorticoid receptor in cell-free supernatant prepared from CEM C7 cells, but this was greatly reduced if ketoconazole and TA were incubated with intact cells prior to preparation of the cell-free supernatant. Ketoconazole inhibited induction by TA of the enzyme glutamine synthetase only at concentrations of 45-90 microM. We conclude that ketoconazole antagonism of glucocorticoid activity in CEM-C7 cells is probably not of pharmacologic significance due to the large concentrations required, and its reduced interaction with receptors in intact cells. The growth inhibitory activity of ketoconazole may be of interest in cancer chemotherapy. PMID- 2894484 TI - A novel superfusion chamber for the measurement of endogenous glutamate release from cerebellar slices. AB - Methods are described for use in the study of potassium-stimulated release of endogenous glutamate and aspartate from perfused cerebellar slices using high performance liquid chromatography (HPLC) with fluorometric detection. Slices were cut at 250 micron in one direction only, and were thus similar to those used for electrophysiological techniques. Details of an easily constructed, simple superfusion system are given. HPLC isocratic separation was used to assay aspartate and glutamate release, glutamate alone showing calcium-dependent release. Repetitive pulses of high potassium-containing artificial cerebrospinal fluid induced release of glutamate (six pulses), demonstrating that the tissue was viable and capable of repeated release. PMID- 2894485 TI - Feasibility of continuous glutamate monitoring in perfused retinal tissue with a potentiometric biosensing probe. AB - A potentiometric biosensing probe for glutamate has been evaluated as a possible tool to measure the release of glutamate from the isolated retina of Bufo marinus. This probe is based on carbon dioxide detection, following enzymatic conversion of glutamate to gamma-aminobutyric acid (GABA) via glutamic acid decarboxylase (GAD). Probe response characteristics of dynamic range, limit of detection, pH dependency, and selectivity are described. Probe modifications were required for sensor operation in an upside down configuration which was demanded by the need to mount and perfuse the retinal tissue directly at the sensor tip. Overall, these results indicate that this particular potentiometric biosensor is not well suited for direct glutamate measurements in retinal tissue because of pH incompatibility between the sensor and the tissue, and because of high background carbon dioxide levels released from the retina at the pH optimum of the probe. Despite this drawback, the sensor could be utilized to provide a continuous "downstream" monitor of glutamate levels during the course of an experiment, after pH buffering of tissue perfusate. Alternative approaches to probes more compatible with direct tissue measurements are discussed. PMID- 2894487 TI - Ultra-short-acting beta-adrenergic blockers. AB - The ultra-short-acting beta-adrenergic blockers are parenteral agents that can be rapidly titrated in clinical situations where immediate beta-adrenergic blockade is warranted. The effects of those drugs rapidly dissipate after termination of treatment, providing an important safety feature. Esmolol, the prototype drug of this class, is approved for treatment of supraventricular tachyarrhythmias but also has potential use in treatment of patients with perioperative hypertension and acute myocardial ischemia. PMID- 2894486 TI - Some features of age-related insulin responsiveness in rat hepatocytes. AB - Different features of insulin sensitivity have been considered, in rat hepatocytes, with respect to their age-dependence. In particular, plasma membrane located responses such as (Na/K)-ATPase and Na-dependent aminoacid transport were studied together with cytoplasmic responses such as the insulin-stimulated tyrosine aminotransferase. It appears, as far as the insulin sensitivity is concerned, that the age of the animal does not affect plasma membrane-bound events whereas plasma membrane-mediated intracellular responses are definitely impaired. Insulin binding to intact hepatocytes does not seem to be age dependent. PMID- 2894488 TI - Terazosin: a new long-acting alpha 1-adrenergic antagonist for hypertension. AB - Terazosin is a new long-acting, selective alpha 1-adrenergic antagonist. Its pharmacokinetic and pharmacodynamic profiles are similar to those of prazosin, but terazosin has a half-life three to four times longer. This allows once daily dosing of terazosin and a potential advantage in ensuring patient compliance to treatment. Terazosin has been evaluated alone and in combination with other drugs for the treatment of mild to moderate hypertension. Terazosin has been shown to have favorable lipid and side effect profiles. Unlike prazosin, the drug is available (but not yet marketed) in parenteral form. Its gradual onset of action with intravenous use would limit its potential application in hypertensive emergencies. Other possible uses for terazosin might include treatment of congestive heart failure and Raynaud's phenomenon, but definitive studies are needed. PMID- 2894489 TI - Pharmacological profiling of cardiovascular agents in healthy volunteers by means of non-invasive methods. AB - In a placebo-controlled study the hemodynamic effects of single doses of oxprenolol, metoprolol, prenalterol, phentolamine, nifedipine, nitroglycerin, angiotensin II and frusemide have been investigated in 9 healthy volunteers by means of the combined measurement of heart rate, blood pressure, pre-ejection period (systolic time intervals) and stroke volume (impedance cardiography) in the supine and tilted positions (70 degrees). Each cardiovascular agent exhibited its characteristic pharmacodynamic profile, which allowed a clear-cut discrimination. The effects of oxprenolol and metoprolol, however, could not be distinguished by this procedure. The pre-ejection period, although not a very specific parameter, proved to be most sensitive to the pharmacological interventions, whereas stroke volume was less often influenced. It is concluded that the proposed selection of non-invasive parameters is a very suitable and simple means for early cardiovascular drug testing in man. PMID- 2894490 TI - Effect of intravenous APSAC on mortality after acute myocardial infarction: preliminary report of a placebo-controlled clinical trial. AIMS Trial Study Group. AB - A randomised double-blind placebo-controlled clinical trial was undertaken to assess survival after a single 30 unit intravenous dose of anisoylated plasminogen streptokinase activator complex (APSAC) within 6 h of onset of acute myocardial infarction. A planned interim analysis of mortality data was undertaken after 1004 patients had been followed for at least 30 days after randomisation. 61 (12.2%) of 502 patients on placebo died within 30 days compared with 32 (6.4%) of 502 patients on APSAC (p = 0.0016). Because of this 47% reduction in 30-day mortality (95% confidence interval 21-65%) patient entry to the trial was terminated. Preliminary 1 year mortality data show a similar trend. Percentage mortality reduction with APSAC was similar whether time since onset of symptoms was 0-4 h (660 patients) or 4-6 h (344 patients). Adverse events were few. These findings add to evidence that intravenous thrombolytic therapy after myocardial infarction offers a substantial reduction in mortality. PMID- 2894491 TI - Aetiological association of a virus-like particle with enterically transmitted non-A, non-B hepatitis. AB - Virus-like particles, approximately 27 nm in diameter, were identified in faeces from an Indian patient with enterically transmitted non-A, non-B (ENANB) hepatitis. They were serologically distinct from hepatitis A virus (HAV). Nucleic acid extracted from the particles did not hybridize with cDNA probes representing the genomes of HAV, enteroviruses, and cardioviruses. Chimpanzees were experimentally inoculated with faecal suspensions containing this 27 nm particle or with faeces from another case of ENANB hepatitis. Mild histological and biochemical hepatitis developed in these animals and there was serological evidence of infection with the virus-like particle as shown by immunoelectronmicroscopy (IEM). Serological analysis by IEM suggested that this agent or an antigenically similar virus was the aetiological agent of two epidemics and a sporadic case of ENANB hepatitis in India and of an epidemic of the illness in the USSR. Antibody to the particle was found in sera from patients with ENANB hepatitis from various geographic areas over a 30-year period. PMID- 2894492 TI - Rebound increase in bronchial responsiveness after treatment with inhaled terbutaline. AB - To investigate whether cessation of regular beta-agonist treatment results in an increase in bronchial responsiveness, two double-blind, randomised crossover studies were done. Subjects with mild asthma were investigated to determine the course of change in bronchial responsiveness, measured as the provocative dose (PD20) of histamine that caused a 20% fall in forced expiratory volume in 1 s after short-term and longer term treatment with an inhaled beta-agonist. In the first study in 8 subjects, 500 and 2000 micrograms terbutaline thrice in 1 day protected against histamine-induced bronchoconstriction, and the increase in PD20 compared with placebo remained high throughout the day and overnight. In the second study 8 subjects received placebo or terbutaline 750 micrograms thrice daily for 14 days. The protection afforded by terbutaline against histamine induced bronchoconstriction on day 14 was less than that on day 1 by 40% in the morning and 82% in the afternoon. On day 15 PD20 was lower after stopping terbutaline than placebo, with a maximum difference of 1.5 (95% CI 0.6-2.5) doubling-doses of histamine 23 h after the end of treatment. Thus treatment with terbutaline for 1 day did not result in any rebound increase in bronchial responsiveness. Treatment for 2 weeks impaired the ability of terbutaline to protect against histamine-induced bronchoconstriction, and was followed by a rebound increase in bronchial responsiveness after cessation of treatment. PMID- 2894494 TI - Detrimental haemodynamic effects of cyclizine in heart failure. AB - The haemodynamic effects of intravenous cyclizine, an antiemetic that is widely given with opioids in left ventricular failure and myocardial infarction, were studied in 11 patients with severe heart failure. Cyclizine significantly increased systemic and pulmonary arterial pressures, and right and left ventricular filling pressures, and negated the venodilatory effects of diamorphine. The use of cyclizine in patients with heart failure should, therefore, be avoided. PMID- 2894495 TI - Immunological differentiation of pathogenic and non-pathogenic isolates of Entamoeba histolytica. AB - Entamoeba histolytica can act as a harmless commensal organism in the lumen of the large intestine, or can cause invasive amoebiasis. Some workers have suggested that there are two distinct subspecies of this organism, and that only one of these is associated with invasive disease. Present isoenzyme tests to identify the subspecies take several days to analyse: we report a technique that uses immunofluorescence with monoclonal antibodies, takes two days to perform, and may, therefore, assist in the clinical management of patients infected with this organism. PMID- 2894493 TI - Red wine as a cause of migraine. AB - Patients with migraine who believed that red wine but not alcohol in general had a headache-provoking effect on them were challenged either with red wine or with a vodka and diluent mixture of equivalent alcohol content, both consumed cold out of dark bottles to disguise colour and flavour. The red wine, which had a negligible tyramine content, provoked a typical migraine attack in 9 of 11 such patients, whereas none of the 8 challenged with vodka had an attack. Neither red wine nor vodka provoked such episodes in other migrainous subjects or controls. These findings show that red wine contains a migraine-provoking agent that is neither alcohol nor tyramine. PMID- 2894496 TI - Thrombolytic therapy for acute myocardial infarction--round 2. PMID- 2894498 TI - Infant nutrition and cardiovascular disease. PMID- 2894499 TI - Depressive illness and the family. PMID- 2894497 TI - Time to abandon pre-transplant blood transfusion? PMID- 2894500 TI - Magnetic resonance imaging of the musculoskeletal system. PMID- 2894501 TI - Waterborne non-A, non-B hepatitis. AB - Waterborne non-A, non-B hepatitis (NANB) is responsible for outbreaks of hepatitis with a predilection for young adults. The disease is usually mild, except in pregnant women, who have a high case-fatality rate from fulminant hepatic failure. Diagnosis is largely based on the epidemiological findings of faecal contamination of drinking water and serological exclusion of hepatitis A and B virus infection. Histological features of liver biopsy specimens are characteristic and virus-like particles in the stool are aggregated by antibody present in acute and convalescent phase sera of the test subject. NANB is widespread in India and several countries of South-East Asia; it is increasingly recognised in Africa and may occur in Latin America. Control measures include provision of clean water supplies, safe disposal of human excreta, and sound personal and food hygiene practices. Passive immunisation with immunoglobulin derived from healthy donors resident in the countries affected by the disease may protect vulnerable groups. PMID- 2894502 TI - Application of DNA "fingerprints" to paternity determinations. AB - 26 cases of disputed paternity were tested by the methods routinely used in Scandinavian countries and by the DNA "fingerprinting" technique. In all the studied cases the results of DNA analyses were similar to those obtained with the routine examinations based on protein polymorphisms; and, in the cases where even HLA typing did not distinguish between tentative fathers, the results obtained with DNA analyses were unambiguous. PMID- 2894503 TI - Management of dyspepsia: report of a working party. PMID- 2894504 TI - Balancing cost and benefit in treatment of late cancer. PMID- 2894505 TI - Total body water and very-low-calorie diets. PMID- 2894507 TI - Incidence of respiratory tract chlamydial infections and importation of psittacine birds. PMID- 2894509 TI - Apical impulse tenderness: clinical observations in two cultures. PMID- 2894506 TI - How should we monitor gold therapy? PMID- 2894508 TI - Sudden infant death syndrome and diphtheria/tetanus toxoid/pertussis/poliomyelitis immunisation. PMID- 2894510 TI - Asymmetrical loss of glutamate receptor subtype in left hippocampus in schizophrenia. PMID- 2894511 TI - Cerebral arteritis and oral methylphenidate. PMID- 2894513 TI - Etretinate and vision. PMID- 2894512 TI - Severe acne-like lesions caused by amineptine overdose. PMID- 2894514 TI - Acute leukaemia during pregnancy. PMID- 2894515 TI - Reappearance of falciparum malaria in central highland plateaux of Madagascar. PMID- 2894516 TI - Reversibility of airflow obstruction. PMID- 2894517 TI - Friedreich's ataxia in Kathikas-Arodhes, Cyprus. PMID- 2894518 TI - Improvement of muscle performance by chronic electrical stimulation in children with cerebral palsy. PMID- 2894519 TI - Decreasing frequency, with time, of hepatitis B surface antigen positive liver biopsy in hepatitis, cirrhosis, and hepatocellular carcinoma. PMID- 2894520 TI - Response to monoclonal CD7 antibody in rheumatoid arthritis. PMID- 2894521 TI - Why does placebo improve severe limb ischaemia? PMID- 2894523 TI - Respiratory cryptosporidiosis in HIV-positive patients. PMID- 2894522 TI - Snow-and-ice fracture in the UK, a preventable epidemic. PMID- 2894524 TI - AIDS and sex. PMID- 2894525 TI - HIV infection and dioxin exposure: risk factors for Kaposi sarcoma and malignant lymphoma? PMID- 2894526 TI - Pharmacokinetic interactions with methotrexate: is 7-hydroxy-methotrexate the culprit? PMID- 2894528 TI - Cannabis and schizophrenia. PMID- 2894527 TI - Nicotine gum and haloperidol in Tourette's syndrome. PMID- 2894529 TI - Bacterial synergistic infections of skin and soft tissues. PMID- 2894530 TI - Campylobacter pylori and ulcer recurrence. PMID- 2894531 TI - Peptostreptococcus micros in polymicrobial abscesses. PMID- 2894532 TI - Transfusion reactions in haemophiliac caused by sensitisation to ethylene oxide. PMID- 2894533 TI - Staphylococcus epidermidis septicaemia. PMID- 2894534 TI - False positive in prenatal diagnosis of cystic fibrosis. PMID- 2894535 TI - Group A beta-haemolytic streptococcus causing disseminated intravascular coagulation and maternal death. PMID- 2894536 TI - Health maintenance organisations. PMID- 2894537 TI - Is yawning a brainstem phenomenon? PMID- 2894538 TI - Cholesterol synthesis inhibitors in hyperlipidaemia. PMID- 2894539 TI - Transmission of common cold. PMID- 2894540 TI - Lipid-lowering drugs. PMID- 2894541 TI - Low-dose gamma interferon in treatment of rheumatoid arthritis. PMID- 2894542 TI - False negativity with one-step monoclonal assay for hepatitis B surface antigen. PMID- 2894543 TI - Satisfaction after cholecystectomy. PMID- 2894544 TI - 8-Methoxypsoralen and ultraviolet A therapy for cutaneous manifestations of graft versus-host disease. PMID- 2894545 TI - Generic product licences and "originator's confidential data". PMID- 2894546 TI - Endotoxaemia: an early predictor of septicaemia in febrile patients. AB - In 473 consecutive febrile patients a sensitive and rapid chromogenic limulus assay was used to assess the value of endotoxaemia versus bacteraemia for predicting development of the syndrome of septicaemia. In each patient three blood specimens for culture and endotoxin testing were obtained at the onset of fever. Blood pressure, urinary output, and the occurrence of thrombocytopenia and metabolic acidosis were recorded prospectively during three days of follow-up. Septicaemia developed in 19 patients (4%). The sensitivity, specificity, and likelihood ratio for a positive result with the endotoxin assay were 79%, 96%, and 20, respectively. The corresponding indices for bacteraemia were 89%, 78%, and only 4. The results suggest that endotoxaemia is a clinically valid indicator for impending gram-negative septicaemia (positive predictive value 48%) and that the absence of endotoxaemia virtually rules out the risk that septicaemia will ensue (negative predictive value 99%). PMID- 2894547 TI - Perioperative bromocriptine adjuvant treatment for operable breast cancer. AB - Blood levels of prolactin are consistently raised in women who have undergone mastectomy for breast cancer, probably because of the stress of surgery. Since this increase in concentration of a known breast epithelial growth promoter might stimulate proliferation in micrometastatic cells shed at the time of surgery, a pilot study was conducted to try to abolish this effect. 38 patients with suspected operable breast cancer were given either bromocriptine (18) or placebo (20) tablets for 5 days preoperatively and thereafter for 3-10 days. Bromocriptine-treated patients showed significant reductions in prolactin levels and in S-phase fraction of tumour cells within the primary infiltrating carcinoma. There were no major side-effects. Perioperative bromocriptine may provide another approach to adjuvant therapy, possibly combined with endocrine or cytotoxic treatment for patients with axillary nodal metastases. PMID- 2894548 TI - Comparison between simvastatin and bezafibrate in effect on plasma lipoproteins and apolipoproteins in primary hypercholesterolaemia. AB - The ability of simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, to lower lipid levels in 16 patients with primary hypercholesterolaemia was compared with that of bezafibrate in a 16-week, double blind, parallel, placebo-controlled trial that was continued in an open crossover fashion. Simvastatin was better than bezafibrate at lowering total and low density lipoprotein (LDL)-cholesterol and apolipoprotein B concentrations (30.4% [p less than 0.001], 37.3% [p less than 0.001], and 37.8% [p less than 0.001] vs 17.0%, 19.6%, and 24.0%, respectively). Both drugs increased the high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I, but this change was significant only with bezafibrate (p less than 0.05). Bezafibrate and simvastatin reduced triglycerides by 25.6% (p less than 0.001) and 13.7% (p less than 0.05), respectively. Very low-density lipoprotein (VLDL)-cholesterol was significantly reduced only by bezafibrate (44.3%, p less than 0.001). Both drugs were tolerated well and no serious side-effects were noted. The results show that simvastatin was more effective than bezafibrate in lowering total-cholesterol, LDL cholesterol, and apolipoprotein B, while bezafibrate was better at lowering triglycerides and VLDL-cholesterol and at raising HDL-cholesterol and apolipoprotein A-I. PMID- 2894549 TI - Fetal blood sampling in investigation of chromosome mosaicism in amniotic fluid cell culture. AB - 41 pregnancies in which mosaicism had been found on amniotic fluid culture (AFC) were investigated by fetal blood and repeat AFC karyotyping. Results of both investigations, and the infants, were normal in 15 of 16 cases of autosomal trisomy (including trisomies 8, 9, 13, 18, and 21) and in the 8 cases of sex chromosome mosaicism. In 1 case of trisomy 20 mosaicism the fetal blood karyotype and the infant were normal but the repeat AFC showed mosaicism. Abnormality was confirmed in 5 of 11 cases of mosaicism for structural chromosomal rearrangements and in 4 of 6 cases with de-novo supernumerary marker mosaicism. These findings indicate the potential danger of terminating pregnancies because of trisomic mosaicism in AFC, and the importance of identifying the clinical significance of certain chromosome rearrangements which, even in mosaic form, might lead to severe mental and developmental handicap. PMID- 2894550 TI - Extended preservation of the liver for clinical transplantation. AB - A new solution (UW solution) was used for flushing and storage of 17 livers before transplantation. In 9 cases the preservation times exceeded 10 hours (mean 12.7, range 11-20) but all left hospital with good liver function. PMID- 2894551 TI - Effect of deoxyfructoserotonin (DFS) on lepromatous leprosy. AB - To examine the anti-leprosy effect of deoxyfructoserotonin the drug was given in a dose of 10 mg/kg for 6 months to 6 patients with active lepromatous leprosy, in accordance with the WHO-THELEP protocol. Clinical and histological assessment and mouse foot-pad studies suggest that the drug has some anti-leprosy effect. PMID- 2894552 TI - Detention of schoolchildren in South Africa. PMID- 2894553 TI - Breast not necessarily best. PMID- 2894554 TI - Much more light on port-wine stains. PMID- 2894555 TI - Acute tropical polyarthropathy: homogeneous entity or diagnostic scrap-heap? PMID- 2894556 TI - Sudden cardiac death in obesity and hypertension. PMID- 2894557 TI - Slimming and serotonin. PMID- 2894558 TI - Epidemic yellow fever in eastern Nigeria, 1986. AB - An epidemic of yellow fever occurred in the eastern part of Nigeria during the second half of 1986. Oju, in Benue State, was the most heavily affected region, but yellow fever also occurred in surrounding areas, particularly Ogoja, in Cross River State. In Oju, the mean attack and mortality rates were 4.9% and 2.8%, respectively. Sex and age specific rates were highest in males and in the 20-29 yr age group. The overall case fatality rate was approximately 50%. Diagnosis was confirmed by IgM capture enzyme-linked immunosorbent assay (ELISA) and complement fixation (CF) tests. Entomological investigations implicated Aedes africanus as the epidemic vector. Oju alone probably had about 9800 cases of yellow fever with jaundice, and some 5600 deaths. Outbreaks of this nature could be prevented by inclusion of yellow fever in the Expanded Programme on Immunisation, in areas subject to recurrent epidemics. PMID- 2894559 TI - Trends in cancer mortality: US white males and females, 1968-83. AB - From 1968 to 1983, age-specific cancer mortality for all cancers fell by 2.1% annually for men and women aged 35-44 and rose by 1.1% annually for men and 0.3% for women aged 75-84. In the 75-84 age group brain cancer mortality rose by 8% annually and multiple myeloma by 2.75%. Lung cancer mortality rose in men and women aged 45-84 (by 8.2% annually in 65-74 year-old women) but fell by over 3% annually in men aged 35-44. Stomach cancer declined by 4% annually in 75-84 year olds and about 3% annually in 55-74 year-olds. These trends do not support the hypothesis that recent increases in specific cancers in the elderly chiefly reflect improved diagnosis of cases that would formerly have been misrepresented or miscoded. PMID- 2894560 TI - 25 years of implanted intracardiac pacers. AB - In 1962, a simplified method of transvenously inserting an intracardiac electrode and implanting the whole pacemaker system under local anaesthesia was reported from the Karolinska Hospital in Stockholm. This simplified method has been universally adopted and pacemakers are now probably implanted too freely in many places. In the Stockholm area pacemakers are implanted half as frequently as in the rest of Sweden and as often as in the United Kingdom. PMID- 2894561 TI - Failure to substantiate two cases of alleged occupational radiation carcinogenesis. PMID- 2894562 TI - Neonatal lupus syndrome: optimism justified? PMID- 2894564 TI - Prader-Willi syndrome and paternal hydrocarbon exposure. PMID- 2894563 TI - Gastric bypass surgery as maternal risk factor for neural tube defects. PMID- 2894565 TI - Unrecognised hazard of urethral lubrication. PMID- 2894566 TI - Craniopharyngioma recurrence and growth hormone therapy. PMID- 2894568 TI - Delayed CSF reaction to praziquantel. PMID- 2894567 TI - Lithium clearance. PMID- 2894569 TI - Cholesterol embolisation after angiography. PMID- 2894570 TI - Blood pressure, erythropoietin, and nitric oxide. PMID- 2894571 TI - Inactivation of HIV by nonoxynol-9. PMID- 2894572 TI - Tetracycline for borrelia encephalitis. PMID- 2894573 TI - Nebulised pentamidine. PMID- 2894574 TI - Herpes simplex virus neonatal encephalitis. PMID- 2894575 TI - Antibodies to plasmid-encoated proteins of enteropathogenic Yersinia in patients with autoimmune thyroid disease. PMID- 2894577 TI - Bilingual consultation. PMID- 2894576 TI - Mifepristone and induction of labour in second half of pregnancy. PMID- 2894578 TI - Fractures of the nose. PMID- 2894579 TI - Penalising smokers and drinkers. PMID- 2894580 TI - Updated Kiel classification. PMID- 2894581 TI - Airway management during cardiopulmonary resuscitation. PMID- 2894582 TI - Painless lithotripsy. PMID- 2894583 TI - Identity of HTLV-I-associated tropical spastic paraparesis and HTLV-I-associated myelopathy. PMID- 2894585 TI - Pulse oximetry in children with bronchopulmonary dysplasia. PMID- 2894584 TI - Tetracycline-resistant gonococci in UK. PMID- 2894586 TI - Preservation of certain voluntary muscles in motoneurone disease. PMID- 2894588 TI - Peripheral adrenoceptors and type A behaviour. PMID- 2894587 TI - Coronary thrombolysis and myocardial salvage by tissue plasminogen activator. PMID- 2894589 TI - NSAIDs, plasma half-lives, and adverse reactions. PMID- 2894590 TI - Dominant inheritance of atopic immunoglobulin-E responsiveness. PMID- 2894591 TI - Meningitis after BCG vaccination. PMID- 2894593 TI - Direct intraperitoneal insemination. PMID- 2894592 TI - Desmopressin and sheared platelets: a test. PMID- 2894594 TI - Isotretinoin dose and teratogenicity. PMID- 2894595 TI - Finger clubbing. PMID- 2894596 TI - Possible case of HBV-2 infection. PMID- 2894597 TI - Management strategies for HIV in obstetrics. PMID- 2894598 TI - Meningioma misdiagnosed as senile dementia. PMID- 2894599 TI - Penicillin-insensitive meningococci in the UK. PMID- 2894600 TI - Hypochloraemic alkalosis after high-flux continuous haemofiltration and continuous arteriovenous haemofiltration with dialysis. PMID- 2894601 TI - Differential effects after repeated treatment with haloperidol, clozapine, thioridazine and tefludazine on SNC and VTA dopamine neurones in rats. AB - The effects of repeated treatment (21 days) with different antipsychotic compounds (haloperidol, clozapine, thioridazine and tefludazine) on dopamine (DA) neurones in substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) were studied in rats using single unit recording techniques. A dose-dependent decrease in the number of spontaneously active DA neurones in SNC and in VTA was observed with haloperidol. Clozapine showed no significant effect on the activity in SNC while a dose-dependent decrease in the number of active DA neurones in VTA was observed. Thioridazine showed no or weak effect in SNC while repeated treatment induced a marked inhibitory effect on the DA neurones in VTA. Tefludazine, a potential antipsychotic compound, induced a dose-dependent decrease in both SNC and VTA DA activity. However, the effect on the DA neurones in VTA was more pronounced at all doses. Since the classical neuroleptic haloperidol is equally effective in both regions, while the atypical neuroleptics clozapine and thioridazine have selective or predominant effect in the VTA area it has previously been thought that the inhibition of spontaneously active DA neurones in VTA should indicate an antipsychotic effect of a compound while the inhibition of DA neurones in SNC should account for the development of neurological side effects. The data suggests that the potential antipsychotic compound tefludazine should not induce neurological side effects at lower doses but still has an antipsychotic activity while repeated treatment with higher doses of tefludazine might cause extrapyramidal side effects. PMID- 2894602 TI - Involvement of kappa type opioids on ethanol drinking. AB - The effects of the administration of the kappa agonist dynorphin1-17 and/or the kappa antagonist MR-2266-BS on ethanol preference was investigated using a paradigm by which rats develop alcohol preference. Administration of dynorphin shortly before or after the conditioning session (forced ethanol exposure) failed to affect later ethanol preference. However, dynorphin treatment prior to the first choice session reduced ethanol preference during the three consecutive testing days. This effect was reversed by the simultaneous administration of the kappa antagonist MR-2266-BS. The results of the present study provide further support for evidence of the involvement of dynorphinergic systems on drinking behavior and suggest that kappa-type opioid mechanisms may be involved in the consumption and development of preference to ethanol in rats. PMID- 2894603 TI - A dynorphin peptide induces hypotension by stimulating the release of atrial natriuretic peptide from rat atrium. AB - Intravenous injection of dynorphin A-(1-10) amide (Dyn, 81-324 nmol/kg) induced a dose-dependent hypotensive effect in the rat. This effect was antagonized by pretreatment with immunoglobulin G, purified from a specific antiserum raised against alpha-human atrial natriuretic peptide (anti-hANP-IgG), as well as by high doses of naloxone (2 or 10 mg/kg). In addition, a 12-fold increase in plasma level of atrial natriuretic peptide-like immunoreactivity (ANP-IR) was found following Dyn administration, which was accompanied by a significant decrease of atrial ANP-IR. These results suggest that the stimulated release of ANP-IR from the atrium may constitute one of the mechanisms for the depressor effect of dynorphin peptides. PMID- 2894604 TI - Huntington's disease: studies on brain free amino acids. AB - We studied the levels of free amino acids in putamen and Brodmann's area 10 of 12 patients who died with Huntington's disease and 13 non-neurologic controls. GABA, glutamate and alpha-amino-n-butyric acid concentrations were found to be reduced in putamen of Huntington's disease patients. In Brodmann's area 10 the levels of glutamate, histidine and lysine were decreased, but the content of aspartate, GABA, glycine, serine and taurine was increased in the same group of patients. PMID- 2894606 TI - [Training of paramedical personnel in Grodno (1864-1917)]. PMID- 2894605 TI - The Paw test: an animal model for neuroleptic drugs which fulfils the criteria for pharmacological isomorphism. AB - Recently we have developed an animal model which could discriminate between classical and atypical neuroleptic drugs: the PAW TEST. This test measures the ability of rats to spontaneously withdraw its force- and hindlimbs. It was found that the ability of drugs to affect the rat's forelimb retraction time was associated with the liability of the drug to induce so-called extra-pyramidal side-effects in man. Likewise the ability of drugs to affect the rat's hindlimb retraction time was associated with the antipsychotic efficacy of the drug. These data open the perspective that the forelimb retraction time (FRT) is an animal analogue of parkinsonian side-effects, and that the hindlimb retraction time (HRT) is an animal analogue of antipsychotic effects In the present series of experiments we further evaluated the validity of these notions by applying the criteria of "pharmacological isomorphism" as proposed by Matthysse (1). Thus HRT had to fulfil the criteria of pharmacological isomorphism for the therapeutic effects of neuroleptics, whereas FRT had to fulfil these criteria for the parkinsonian side-effects. The results of the present study show that both FRT and HRT met these criteria. Thus both classical and atypical neuroleptics were effective in prolonging HRT, whereas only the classical neuroleptics prolonged FRT (criterion 1); the nonneuroleptic phenothiazine promethazine (as well as the narcotic morphine, the muscle relaxant diazepam and the antidepressant desipramine) were ineffective in this respect (criterion 2); the acetylcholinergic antagonist scopolamine blocked the FRT, but not the HRT (criterion 3); chronic neuroleptic treatment reduced the FRT, but not the HRT (criterion 4). In conclusion the paw test, an animal model for testing antipsychotic drugs, was found to fulfil the criteria for "pharmacological isomorphism". Although the exact mechanism underlying the paw test is as yet unknown, the present data improve its validity as an animal model. PMID- 2894607 TI - [Hygienic requirements for the class lessons of schoolchildren]. PMID- 2894608 TI - Neuropeptides in Alzheimer's and in Parkinson's disease. PMID- 2894609 TI - Effects of dietary amino acids, carbohydrates, and choline on neurotransmitter synthesis. PMID- 2894611 TI - Open reading frames and translational control. PMID- 2894610 TI - Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. AB - Multiple endocrine neoplasia type 1 (MEN-1) is a predisposition to hyperplasia of the parathyroid glands, and to hyperplasia or tumours of the anterior pituitary and the endocrine pancreas, and is inherited as an autosomal dominant trait. Here we map the MEN-1 locus to chromosome 11 by family studies, and demonstrate tight linkage with the human muscle phosphorylase gene. By comparing constitutional and tumour tissue genotypes of insulinomas from a pair of brothers who had inherited MEN-1 from their mother, we have shown that oncogenesis in these cases involves unmasking of a recessive mutation at this locus. PMID- 2894612 TI - Identification and characterization of E. coli type-1 pilus tip adhesion protein. AB - The type-1 pilus of Escherichia coli is the prototype of this class of hair-like, multimeric adhesive organelles. This pilus mediates adherence to mannose containing receptors on mucosal epithelia and other cells. The type-1 pilus, in one of several serological variants, is expressed by nearly all E. coli strains, and its promotion of colonization by pathogenic bacteria and the protective effects of purified pilus vaccines suggest that it is important as a bacterial virulence factor. Both the adhesive function and the serological variation of the type-1 pilus have been attributed to the thousand or so pilin protein monomers making up the pilus rods. This idea has been contradicted by our earlier observations on an E. coli strain expressing adhesion-defective pili. More recent genetic evidence also indicates that auxiliary pilus proteins are required for adhesive function. We report here the identification of three previously undetected integral minor proteins on the type-1 pilus, and show that one of them is the receptor-binding adhesin. This protein is antigenically conserved among strains with different pilin serotypes and is located at the pilus tip. PMID- 2894613 TI - Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. AB - Von Hippel-Lindau disease (VHL) is an autosomal dominant disorder with inherited susceptibility to various forms of cancer, including hemangioblastomas of the central nervous system, phaeochromocytomas, pancreatic malignancies, and renal cell carcinomas. Renal cell carcinomas constitute a particularly frequent cause of death in this disorder, occurring as bilateral and multifocal tumours, and presenting at an earlier age than in sporadic, non-familial cases of this tumour type. We report here that the VHL gene is linked to the locus encoding the human homologoue of the RAF1 oncogene, which maps to chromosome 3p25 (ref. 4). Crossovers with the VHL locus suggest that the defect responsible for the VHL phenotype is not a mutation in the RAF1 gene itself. An alternative or prior event to oncogene activation in tumour formation may be the inactivation of a putative 'tumour suppressor' which can be associated with both the inherited and sporadic forms of the cancer. Sporadic renal cell carcinomas have previously been associated with the loss of regions on chromosome 3p (refs 5, 6). Consequently, sporadic and VHL-associated forms of renal cell carcinoma might both result from alterations causing loss of function of the same 'tumour suppressor' gene on this chromosome. PMID- 2894614 TI - Synaptic investment of striatal cellular domains by grafted dopamine neurons in weaver mutant mice. PMID- 2894615 TI - [Neuroleptics as anxiolytics and antidepressive agents]. PMID- 2894617 TI - Chronic treatment with imipramine does not reverse the effects of 3 anxiogenic compounds in a test of anxiety in the rat. AB - The ability of chronic treatment with imipramine (an antidepressant with anti panic activity) to antagonise the anxiogenic effects of 3 different compounds was investigated in the elevated plus-maze. The compounds chosen are likely to produce anxiety by activity at different sites in the central nervous system: yohimbine, by blocking the alpha 2-adrenoceptor; FG 7142, by action at the beta carboline site on the GABA-benzodiazepine receptor complex and pentylenetetrazole, by acting at the picrotoxinin site on this complex. Administration of imipramine following 21 days pre-treatment did not produce a significant consistent anxiolytic effect alone and was unable to reverse the anxiety produced by any of the 3 anxiogenic compounds. Our results are discussed in terms of the nature of the anxiety produced by the anxiogenic drugs and the sensitivity of tests of anxiety to anti-panic agents. PMID- 2894616 TI - Effects of medium glutamine, glutamate, and ammonia on glutamine synthetase activity in cultured mouse astroglial cells. AB - Mouse astroglial cells were grown during the last week of culture in either glutamine-free or glutamine-containing medium. The addition of cortisol to the glutamine-containing medium resulted in a doubling of astroglial glutamine synthetase (GS) activity. Withdrawal of glutamine from the medium resulted in a 50% elevation of GS and addition of cortisol to such a medium resulted in a further increase in GS which was not additive to glutamine withdrawal. Both in glutamine-free and glutamine-containing medium, the addition of glutamate resulted in a depression of both basal and cortisol induced GS activity. The simultaneous addition of ammonia plus glutamate to the culture medium ameliorated the glutamate mediated depressive effects on cortisol induced but not basal GS activity. Glutamine withdrawal from the culture medium resulted in an astroglial protein deficit. The addition of ammonia to the medium considerably reduced this deficit and the addition of glutamate completely eliminated this protein deficit. PMID- 2894618 TI - Urinary enzyme excretion during treatment of malignancies with human recombinant alpha-2 interferon. PMID- 2894619 TI - Increase in K+-stimulated, Ca2+-dependent release of [3H]glutamate from rat dentate gyrus three days after induction of long-term potentiation. AB - Long-term potentiation (LTP) was induced by unilateral tetanic stimulation of the perforant path in the dentate gyrus of rats with implanted electrodes. Evoked potentials were monitored for the subsequent 3 days in one group, and for 23 days in another. The dentate gyrus was removed bilaterally and slices prepared and stored in 10% DMSO/Krebs for subsequent analysis of K+-stimulated, Ca2+-dependent release of [3H]glutamate. In the 3-day group, in which the mean increase in the population EPSP was 35% at the time of sacrifice, release from the tetanized side was significantly greater than from the unstimulated side. In the 23-day group, both the increase in the EPSP and the increase in release from the tetanized side had declined to statistically insignificant levels. These results extend to a period of several days the previously observed association between LTP and increased K+-stimulated, Ca2+-dependent release of transmitter. PMID- 2894620 TI - Inhibitory effect of intraterminal lithium on asynchronous release of excitatory quanta induced by veratridine in nerve-muscle synapses of crayfish. AB - Crayfish muscle fibres were voltage-clamped at E = -80 mV membrane potential and superfused for about 10 min with Li+ saline (Na+ replaced by Li+) which contained picrotoxin to block inhibitory post-synaptic currents. Addition of veratridine (100 mumol/l) caused intense fluctuations in the voltage clamp current within 20 60 s due to vigorous asynchronous quantal release of excitatory transmitter from the nerve terminals distributed over the muscle fibre surface. Most likely, this quantal release resulted from loading the nerve terminals with Li+ via voltage gated Na+ channels activated by veratridine. However, in the presence of Li+ quantal release was only transient; the quantal release rate, n, attained a maximum of congruent to 10,000 quanta/s and then declined exponentially with tau congruent to 10 to 20 s. Removal of Li+ and reapplication of normal Na+ increased n a second time. The amount of quanta released in the presence of Na+ was about an order of magnitude larger than that released previously in the presence of Li+. In preparations pretreated with Li+ superfusate for t greater than 45 min no marked quantal release could be elicited by veratridine. The experiments suggest an inhibitory effect of intraterminal Li+ on the quantal release process. PMID- 2894621 TI - Postnatal development of phenylethanolamine-N-methyltransferase activity of rat retina. AB - The postnatal development of rat retinal phenylethanolamine-N-methyltransferase (PNMT) activity was measured by radiometric assay. Activity was detected on day 1 of life. Retinal PNMT activity of day 1 neonates approximated 10% that of the adult. There is an increase in enzyme activity before eye opening. By day 30, enzyme activity has peaked. The enzyme during this early period possesses the same substrate specificity and inhibitor sensitivity as that of the adult enzyme. PNMT activity is detected before tyrosine hydroxylase activity. PMID- 2894622 TI - Argiopin blocks the glutamate responses and sensorimotor transmission in motoneurones of isolated frog spinal cord. AB - Argiopin, a low-molecular weight component of the spider Argiope lobata venom, inhibited depolarizations of motoneurones induced by glutamate in experiments on the frog isolated spinal cord, but had no effect on aspartate-induced responses. Half of the blocking effect (ED50) was seen at 7.5 +/- 3.7 x 10(-8) M argiopin. The same concentrations of argiopin (7.5 x 10(-8) M to 2.3 x 10(-7) M) suppressed the responses of the ventral root to electrical stimulation of the dorsal root. The results suggest that argiopin selectively blocks only one population of the excitatory amino acid receptors on motoneurones, and these argiopin-sensitive receptors are found to be involved in sensorimotor synaptic transmission in the spinal cord. PMID- 2894623 TI - Phencyclidine depresses transmitter release at the neuromuscular synapse of the locust. AB - The presynaptic effects of phencyclidine (PCP) were studied in the locust extensor tibiae muscle. The neurally evoked transmitter release is diminished in the presence of 5 x 10(-6) to 5 x 10(-5) M PCP. This is indicated (1) by an increased coefficient of variation of the excitatory junction potentials; (2) by an increased rate of failures (a) with nerve stimulation in low [Ca2+]saline and (b) with focal extracellular stimulation in normal [Ca2+]saline. The rate of spontaneous transmitter release is not affected. PMID- 2894624 TI - Quisqualate and N-methyl-D-aspartate (NMDA) receptors in induction of hippocampal long-term facilitation using conditioning solution. AB - Brief electrical high-frequency stimulation (tetanus) via the synapses induces long-term potentiation (LTP) in hippocampal neurons. In order to elucidate how LTP is produced, we attempted to induce long-term facilitation (LTF) by perfusing a conditioning solution (CS) instead of the tetanus. A 5 min perfusion of hippocampal slices with a CS containing glutamate, K+ at high concentration and no Mg2+ resulted in the generation of LTF in CAl and dentate neurons. CS lacking one of these 3 factors failed to produce LTF. When the glutamate of the CS was substituted by both quisqualate and N-methyl-D-aspartate (NMDA), LTF was initiated. This indicates that both quisqualate and NMDA receptors play an important role in the induction of LTP. PMID- 2894625 TI - Two populations of tyrosine hydroxylase-positive cells occur in the spinal cord of the chick embryo and hatchling. AB - The existence of tyrosine hydroxylase (TH)-containing neurons in the spinal cord of the chick embryo was investigated by anti-TH immunocytochemistry. Two populations of intensely immunostained cells were observed along the entire extent of the cord, beginning late in chick embryogenesis. One group of TH positive cells was particularly numerous and found ventral to the central canal. The other group, which was smaller in number, was located along the superficial and lateral border of the dorsal horn of the spinal cord. When examined by the glyoxylic acid histofluorescence technique, cells could be visualized only very infrequently ventral to the central canal, and not at all within the dorsal horn. However, after pretreatment of hatchlings with the catecholamine synthesis precursor L-DOPA, cells ventral to the canal were readily observed by histofluorescence, while the dorsally located cells seldom visualized. Since these populations of TH-positive cells appear to only partially express the catecholaminergic phenotype, these cells may provide a model in which factors regulating the expression of neurotransmitter phenotypes can be examined in neurons of the developing CNS. PMID- 2894626 TI - Quantitative autoradiographic localization of alpha 2-antagonist binding sites in rat brain using [3H]idazoxan. AB - The distribution of alpha 2-receptors was determined by quantitative autoradiography with the antagonist [3H]idazoxan. Apart from regions which are known to be enriched in alpha 2-receptors, the highest silver grain densities were located over the subfornical organ and the area postrema. However, binding in these regions was not displaced by yohimbine and therefore, according to the present understanding, cannot be considered to represent alpha 2-receptors. Within the cerebellum, alpha 2-receptors were found to be arranged in 3 sagitally oriented strips within the molecular layer of lobules 9 and 10, suggesting a co incidence with dopamine and substance P receptors in this structure. PMID- 2894627 TI - Epileptiform activity induced by alkalosis in rat neocortical slices: block by antagonists of N-methyl-D-aspartate. AB - The effects of changing extracellular pH on epileptiform activity induced by the removal of magnesium ions from the perfusing medium were studied. The proportion of bicarbonate in the artificial cerebrospinal fluid and of CO2 in the gas mixture were altered to mimic metabolic and respiratory acid-base disturbances. Changes in pH of 0.2 unit from control produced marked effects. Epileptiform activity was enhanced by alkalosis and diminished by acidosis. In normal magnesium-containing medium metabolic alkalosis (pH greater than 7.8) induced spontaneous epileptiform activity that was blocked by selective N-methyl-D aspartate antagonists. The relevance of these findings to acid/base changes in clinical epilepsy is discussed. PMID- 2894629 TI - Diet and maintenance of mental health in the elderly. PMID- 2894628 TI - Dynorphin1-17 reduces the inhibitory actions of mu- and delta-selective opioid agonists in cortical neurons of the rat in vivo. AB - Spontaneous and L-glutamate-evoked neuronal activity was recorded extracellularly from neocortical neurons of rats. Opioid agonists with preference for different receptor types were applied microiontophoretically or pneumatically from multibarrelled micropipettes. Morphine (mu-selective), [D-Ala2,D-Leu5]enkephalin (delta-selective; DADL) and the kappa-selective agonist dynorphin1-17 (DYN 17) suppressed spontaneous and evoked neuronal activity in a naloxone-reversible manner. In a substantial number of neurons the inhibitory effect of DADL and morphine was reduced or abolished by DYN 17. This antagonistic action was often observed with DYN 17 levels that did not influence the discharge activity by itself. The physiological significance of this observation remains to be elucidated. PMID- 2894630 TI - The Third International Conference on AIDS: risk of AIDS in healthcare workers. PMID- 2894631 TI - [A method of plastic surgery of soft tissue defects of the heel and sole regions of the foot]. PMID- 2894632 TI - [Anaerobic infection of bones and joints]. PMID- 2894635 TI - Styl RFLP recognised by a human IRBP cDNA localised to chromosome 10. PMID- 2894634 TI - Xenopus homeobox-containing cDNAs expressed in early development. AB - We report the isolation of six different homeobox-containing genes in Xenopus laevis which are expressed during early embryogenesis. cDNA clones of all of them were partially sequenced including two from previously isolated Xenopus genomic loci and found to contain homeodomains which share a high degree of homology with the Antennapedia protein (50 to 59 out of 60 amino acids). We find a short region of homology (consensus Ile Tyr Pro Trp Met) in four of the cDNAs, which is also present in Antennapedia and that may correspond to a bend region preceding the homeodomain. Northern blots have been performed to show the transcriptional pattern through early frog embryogenesis. Three of the genes are expressed only during a very narrow period of embryogenesis, reinforcing the view that homeobox genes are developmentally regulated. PMID- 2894633 TI - Functional activity of the two promoters of the myosin alkali light chain gene in primary muscle cell cultures: comparison with other muscle gene promoters and other culture systems. AB - Proximal upstream flanking sequences of the mouse myosin alkali light chain gene encoding MLC1F and MLC3F, the mouse alpha-cardiac actin gene and the chicken gene for the alpha-subunit of the acetylcholine receptor were linked to the bacterial chloramphenicol acetyl transferase (CAT) gene and transfected into primary cultures derived from mouse skeletal muscle or into myogenic cell lines. We demonstrate that the mouse MLC1F/MLC3F gene has two functional promoters. In primary muscle cultures, a 1200 bp sequence flanking exon 1 (MLC1F) and a 438 bp sequence flanking exon 2 (MLC3F) direct CAT activity in myotubes, but not in myoblasts or in non myogenic 3T6 and CV1 cells. Developmentally regulated expression is also seen with the alpha-cardiac actin (320 bp) and acetylcholine receptor alpha-subunit (850 bp) upstream sequences in the primary culture system. Transfection experiments with myogenic cell lines show different results with a given promoter construct, reflecting possible differences in the levels of regulatory factors between lines. Different muscle gene promoters behave differently in a given cell line, suggesting different regulatory factor requirements between these promoters. PMID- 2894636 TI - D22S15--a fetal brain cDNA with BanII and SacI RFLP. PMID- 2894637 TI - A high frequency NcoI RFLP detected in the Alzheimer amyloid peptide gene. PMID- 2894638 TI - A DNA probe, D5 [D4S90] mapping to human chromosome 4p16.3. PMID- 2894639 TI - An MPO cDNA clone identifies an RFLP with PstI. PMID- 2894640 TI - A human single copy DNA probe (ZB6-1) detects multiple polymorphisms on 6q. PMID- 2894641 TI - A fragment of the human c-Ki-ras1 pseudogene (HGM9 gene symbol KRAS1P), localized to 6p12-p11, detects 3 allele, RFLP. PMID- 2894642 TI - [Beta 2 stimulants in the therapy of childhood asthma]. AB - Bronchial obstruction, chronic or acute, is due to different anatomical and functional events, mainly to smooth muscular contraction and oedema and secretions. In the first age of life the secretions and thickness of bronchial wool are the most important factors due to small bronchial caliber and poor muscular component. In the older child the most important cause is determined by the reactive spasm of bronchial smooth muscle. PMID- 2894643 TI - [Evaluation of the testicular function using the HCG test in normal and cryptorchid children]. AB - The testicular function has been evaluated by a single dose hCG-test in normal and cryptorchid prepubertal boys using three different protocols. No remarkable difference has been observed using different posologic protocols. Testicular function in boys affected by cryptorchidism was similar to the testicular function in normal controls. However cryptorchid boys older than 6 years of age showed a significant reduction in testicular response to hCG-test in comparison to cryptorchid boys younger than 6 years of age. PMID- 2894644 TI - Pharmacological activities of the MIF-1 analogues Pro-Leu-Gly, Tyr-Pro-Leu-Gly and pareptide. AB - The pharmacological activities of the related free acid analogues of MIF-1, Pro Leu-Gly (PLG) and Tyr-Pro-Leu-Gly (YPLG), were investigated because of the possibility that they may be formed during the digestion of milk and wheat proteins in vivo. The amino acid sequences -Tyr-Pro-Leu-Gly- and -Pro-Leu-Gly- are present in proteins from these foods. Chronic administration of either PLG (0.25 mg/kg, SC, BID) or the control substance, pareptide (0.25 mg/kg, SC, BID), antagonized the development of tolerance to the cataleptic effects of haloperidol in mice. The effect of YPLG (0.25 mg/kg, SC, BID) on the development of this tolerance was borderline and not statistically significant. Nanomolar concentrations of PLG, YPLG, and pareptide each increased the in vitro binding of 3H-apomorphine to rat striatal receptors. In this in vitro system, bell-shaped dose response curves were observed for each peptide. The effects of these peptides on tolerance development and apomorphine binding are similar to those previously reported for MIF-1 and demonstrate that amidation at the carboxyl terminus is not required for biological activity. PMID- 2894645 TI - Effects of food deprivation and high fat diet on immunoreactive dynorphin A(1-8) levels in brain regions of Zucker rats. AB - The levels of immunoreactive dynorphin A(1-8) (ir-DYN8) were measured in discrete brain regions of lean Zucker rats subjected to food deprivation for 72 hr and to a high fat diet, and in fatty Zucker rats after food deprivation for 72 hr. Fatty rats showed higher concentrations of ir-DYN8 in the cortex and midbrain, when compared to lean rats fed a stock diet ad lib. Food deprivation increased ir-DYN8 levels in the cortex of lean rats and fatty rats and in the hippocampus of fatty rats, but decreased its content in the striatum of lean rats and in the midbrain of fatty rats. The high fat diet increased ir-DYN8 levels in the cortex and midbrain of lean rats. These results suggest that ir-DYN8 levels in extrahypothalamic structures of Zucker rats could be differentially modified under conditions of hereditary obesity and dietary manipulations. PMID- 2894646 TI - Cardiovascular effects of dynorphin A (1-13) in conscious rats and its modulation of morphine bradycardia over time. AB - The short-term cardiovascular effects of dynorphin A (1-13), as well as its effects upon morphine bradycardia were investigated. In unanesthetized, unrestrained rats, intracerebroventricular (ICV) dynorphin A (1-13) injections (10-20 micrograms) produced a dose-related pressor effect, whereas intravenous (IV) dynorphin A (1-13) (1.0 mg/kg) produced a depressor effect; these responses persisted less than five min. Heart rate was not significantly altered by these doses or routes of administration. Dynorphin A (1-13) also produced behavioral effects in the unanesthetized animals, such as wet dog shakes in response to IV administration and wet dog shakes accompanied by barrel rolling in response to ICV administration. To evaluate the effects of dynorphin A (1-13) pretreatment on the bradycardic response to IV morphine, rats were pretreated with 10 micrograms dynorphin A (1-13) ICV four, six or eight hours prior to challenge with morphine sulfate (0.1 mg/kg IV). Four hour pretreatment with dynorphin A (1-13) (tested at 14:00 hr) resulted in a potention of morphine bradycardia, with six hours pretreatment (tested at 16:00 hr) no effect was observed, and eight hours following dynorphin A (1-13) pretreatment (tested at 18:00 hr) morphine bradycardia was attenuated. Additionally, the bradycardic response to IV morphine alone became more exaggerated as rats approached their nocturnal activity cycle. These data further establish that dynorphin A (1-13) exerts a potent, long lasting modulatory effect on morphine bradycardia and emphasize the importance of circadian variables in altering the magnitude of cardiovascular responses to opioid agonists. PMID- 2894647 TI - Isolated deficiency of immunocytochemically detected somatostatin in Snell dwarf, but not in "little," mice. AB - Immunocytochemical staining of the neuropeptide somatostatin was evaluated in the brains of two growth hormone-deficient mouse mutants, Snell dwarf (dw/dw), and "little" (lit/lit). In Snell dwarf mice, in which GH is undetectable, an isolated somatostatin deficiency was observed in hypothalamic median eminence and in anterior periventricular hypothalamic neurons which are afferent to median eminence, compared to somatostatin staining in normal mice of the same strain (DW/?). Somatostatin staining in all other CNS areas in dwarfs was identical to that in normal mice. In contrast, in little mice, which exhibit 5-10% of normal GH levels, somatostatin expression was comparable between mutants and normal mice (LIT/?) in all CNS areas, including median eminence-afferent neurons in anterior periventricular hypothalamus. The results suggest that expression of somatostatin in hypophysiotropic CNS is dependent upon minimal pituitary GH secretion. PMID- 2894648 TI - Brain peptide reverses effect of morphine on human lymphocytes. AB - E-rosette formation by human lymphocytes incubated with sheep red blood cells (sRBC) is inhibited by morphine. We studied the ability of the opiate antagonists naloxone and Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) to block this action. Active E rosette formation by lymphocytes incubated with morphine was reduced from the control of 35.7 +/- 1.7% to 23.7 +/- 1.5% (p less than 0.001). Similarly, total E rosette formation was reduced by morphine from the control of 65.8 +/- 1.3% to 53.2 +/- 2.9% (p less than 0.001). These effects were blocked by co-incubation of the lymphocytes with either Tyr-MIF-1 or naloxone (p less than 0.05). Tyr-MIF-1 was active (p less than 0.05) at concentrations as dilute as 10(-13) M. These results indicate that the neuropeptide Tyr-MIF-1 exerts an antiopiate effect at the human T-lymphocyte. PMID- 2894649 TI - Postnatal development of somatostatin levels and its binding sites in rabbit gastric mucosa. AB - Using a specific radioimmunoassay technique, we have determined somatostatin-like immunoreactivity (SLI) in acid extracts of gastric (fundic and antral) mucosa as well as the specific binding of 125I-Tyr11-somatostatin to cytosol of the stomach of 0 to 150 days postnatal rabbits. The levels of somatostatin in both fundus and antrum decreased from birth up to day 5 followed by a sharp increase from 5 to 10 days, then decreased progressively until day 35. After this age, the somatostatin concentration remained relatively stable. The number of specific somatostatin binding sites of both high- and low-affinity increased gradually (without changes in the affinity values) with the development of rabbits, reaching the adult level by 35 days. However, there was an apparent lack of high-affinity sites immediately after birth (day 0). The somatostatin binding sites had characteristics identical with those found in adult animals with regard to their respective specific ligands. PMID- 2894650 TI - 17 beta Estradiol-induced increase in brain dopamine D-2 receptor: antagonism by MIF-1. AB - Animal behavioral and neurochemical studies implicate dopaminergic systems in the neurological sequelae induced by estrogen. In the present study, we demonstrated for the first time that MIF-1, a neuropeptide unrelated to classical dopamine agonists, when given prior to, concurrently with, and after 17 beta-estradiol, antagonized significantly the estrogen-induced increase in the density of dopamine D-2 receptor both in the striatum and the mesolimbic area of male rat brain. The current findings have implications for the prophylactic and therapeutic potential for MIF-1 in extrapyramidal motor disorders caused by estrogen imbalance in humans. PMID- 2894652 TI - A quarter-century of beta blockade. Lessons from the past, an eye toward the future. PMID- 2894653 TI - Treatment of cardiac myopathies with beta blockers. What do we know, where do we go from here? AB - The increase in sympathetic nervous system activity noted in heart failure of several etiologies has beneficial effects in the short term; in the long term, though, it may be detrimental. This provides a rationale for use of beta-blocker therapy in patients with cardiac myopathies of various etiologies. Postinfarction trials in patients with ischemic heart disease have suggested that beta blockade provides a substantial mortality benefit, and beta blockers are accepted as first line therapy for hypertrophic cardiomyopathy. The use of beta-blocking drugs for dilated cardiomyopathy (DCM), however, is currently investigational. Early trials reporting benefits in functional class, exercise capacity, and myocardial function stimulated further interest in this application of beta blockade. Recent studies comparing metoprolol with placebo or standard treatment have shown promising improvements in functional class and exercise capacity. The patients who will benefit most from beta-blocker therapy in DCM may be those with a high resting heart rate and a short duration of symptoms and, perhaps, feminine gender. Marked structural abnormality on cardiac biopsy (eg, fibrosis) may suggest a poor response to treatment. A multicenter controlled study of metoprolol in dilated cardiomyopathy is in progress. If the outcome is favorable, beta-blocker therapy in DCM may become an accepted, rather than an experimental, treatment. PMID- 2894651 TI - Histologic changes in the rat prostate cancer model after treatment with somatostatin analogs and D-Trp-6-LH-RH. AB - Histopathologic changes produced during the treatment of Dunning R3327 prostate cancer with new superactive somatostatin analogs (RC-121 and RC-160) and D-Trp-6 analog of luteinizing hormone-releasing hormone agonist (D-Trp-6-LH-RH) were studied. A significant reduction of the tumor weight could be observed in all treated groups, but the greatest decrease in the tumor volume was seen in the groups receiving the combination of the somatostatin analog and D-Trp-6-LH-RH. Histologically, the treatments resulted in a loss of the tumorous glandular elements and the proliferation of the stromal cells. In the tumors treated with somatostatin analogs, the amount of connective tissue was greatly increased and was accompanied by the appearance of thick collagenous fibers. In the D-Trp-6-LH RH treated groups, regressive changes in the epithelium were seen in addition to the proliferation of connective tissue. The greatest histologic improvement was observed in the group treated with the combination of RC-160 and D-Trp-6-LH-RH. This histopathologic evaluation clearly supports our contention that superactive analogs of somatostatin greatly potentiate the inhibitory effect of D-Trp-6-LH-RH on the growth of Dunning prostate tumors and may improve the clinical response in patients with prostate cancer. PMID- 2894654 TI - Management of arrhythmias in ischemic heart disease. The role of beta blockers. AB - Ventricular arrhythmias can lead to sudden cardiac death (SCD), and they can be classified according to the risk they present. Lethal ventricular arrhythmias, the least common, present the highest risk for SCD and usually manifest as paroxysmal sustained ventricular tachycardia. Most of the patients have serious left ventricular dysfunction and important hemodynamic symptoms, which must be treated immediately. Potentially lethal arrhythmias are much more common, accounting for most SCD cases. The patients generally have coronary artery disease, and the ventricular arrhythmias usually do not cause hemodynamic symptoms. Premature ventricular complexes (PVCs) and nonsustained ventricular tachycardia are the usual forms. PVCs are classified as benign in the absence of coronary artery disease, structural heart disorders, and hemodynamic symptoms, and in these cases the risk for SCD is low. Beta blockers have been shown to reduce the SCD rate, and although the precise mechanism is unknown, the effect may be in part on an antiarrhythmic basis. Like the class IA and IB antiarrhythmic agents (the Vaughan Williams classification), beta blockers are effective in about 50% of patients with either potentially lethal or benign ventricular arrhythmias. However, compared with such agents, beta blockers have a more favorable side effects profile. PMID- 2894655 TI - CNS adrenergic receptors and beta blockade. AB - The changes in noradrenergic and adrenergic activity that regulate beta adrenergic receptors in the CNS have been assessed by lesion studies as well as by pharmacologic enhancement and inhibition of transmission. Beta-adrenergic receptor subtypes are differentially distributed throughout the CNS and are probably differentially regulated. An effect of normal aging on beta receptors has been found in studies of both animal and human brain tissue. Preliminary studies relating to neuropsychiatric disorders in humans and animal studies on the action of antidepressants suggest that CNS beta receptors may play a critical role in affective disorders and their treatment. This may explain why beta blocker medication is associated with side effects such as depression and lethargy, which are generally reversible when selective hydrophilic beta blockers are used or when the therapy is withdrawn. PMID- 2894656 TI - Mitral valve prolapse syndrome. Evidence of hyperadrenergic state. AB - Although mitral valve prolapse (MVP) is a common valvular abnormality, its diagnostic classification has not been well defined. MVP is considered to be an anatomic entity with specific pathologic tissue characteristics and pathophysiologic consequences. The term "MVP syndrome" (MVPS) is used to refer to symptoms due to neuroendocrine or autonomic dysfunction that occur in patients with MVP and that cannot be explained on the basis of valvular abnormality alone. Several studies have shown that patients with MVPS have high urinary epinephrine and norepinephrine excretion, high plasma catecholamine concentrations, abnormal catecholamine response to volume expansion, and hyperresponse to adrenergic stimulation. In patients with MVPS and ventricular arrhythmias, the frequency of premature ventricular contractions parallels the urinary and plasma catecholamine values. The clinical presentation of MVPS may be related in part to high adrenergic tone and/or hyperresponse to adrenergic stimulation. Therefore, certain patients with MVPS and high adrenergic tone may benefit from beta blockade. PMID- 2894657 TI - Can aggressive behavior in humans be modified by beta blockers? AB - Persistent aggressive behavior may develop in patients with brain disorders of various types, including seizure disorders, mental retardation, metabolic disorders, head injury, and in some instances schizophrenia. Although a neurochemical basis for aggression in these cases is unclear, a hyperadrenergic state is considered to be one possibility. This has led to the hypothesis that beta blockers may be useful in the control of aggression. The original assumption was that the site of antiaggressive action of beta blockers is in the brain. However, the antiaggressive efficacy of nadolol, which does not cross the blood brain barrier to any great extent, suggests a peripheral site or sites. A review of several studies in which both old and young aggressive patients with various organic brain disorders received propranolol showed that aggressive behavior was reduced in 75 (86%) of 87. These results are encouraging because none of the patients had responded to earlier drug treatment. However, with the exception of one study of nine patients, none of the studies were controlled for placebo effects and most were retrospective. Preliminary results suggest tentative guidelines for treatment of aggressive behavior with beta blockers. Further studies are needed, and these should use a prospective, longitudinal double-blind design; large enough patient samples to permit testing hypotheses about disease specific or symptom-specific responses to beta blockers; and improved instruments for measuring and classifying aggression. PMID- 2894658 TI - The role of beta blockers in alcohol withdrawal syndrome. AB - Previous studies have suggested that beta blockers might be useful in the treatment of alcohol withdrawal syndrome. A randomized, double-blind clinical trial was therefore conducted to compare results with atenolol versus those with placebo in patients hospitalized with alcohol withdrawal syndrome. In addition to receiving customary therapy, patients were randomly assigned to receive atenolol (61 patients) or placebo (59 patients). Outcome was assessed daily by the measurement of nine features in three categories: vital signs, clinical signs (eg, tremor), and behavioral signs (eg, agitation). Among patients who had withdrawal symptoms at baseline, vital signs became normal more rapidly in the patients receiving atenolol; abnormal behavior and clinical characteristics also resolved more rapidly. On each treatment day, significantly fewer patients receiving atenolol required concomitant oxazepam therapy for agitation. Patients receiving placebo, however, required a significantly higher mean daily dose of oxazepam. The results indicate that atenolol is helpful in the treatment of patients with alcohol withdrawal syndrome. PMID- 2894659 TI - The beta-adrenergic receptor. Configuration, regulation, mechanism of action. AB - Much has been learned in the 25 years since a beta-blocking drug was first administered to humans. The beta-adrenergic receptor has been divided into two general subtypes, and these have been purified to homogeneity. The beta 2 receptor gene has been cloned, and the primary structure of the beta 2 receptor has been deduced. Additionally, important details of the receptor-adenylate cyclase complex have been elucidated. Another general category of information relates to the unique features of the myocardial beta-adrenergic receptor population. These include (1) a relatively high proportion of beta 2 receptors and coupling of these receptors to muscle contraction; (2) the apparent lack of spare receptors; (3) selective down-regulation of the beta 1-receptor population in heart failure, with preservation of the beta 2 and alpha 1 populations; and (4) mediation of the most powerful inotropic stimulus that can be delivered by a receptor-coupled pathway. In the next 25 years, investigations will emphasize the use of molecular biologic techniques to discover crucial information about the control of beta-receptor structure and function. From this research will come both new pharmacologic agents and new applications of currently available agents. PMID- 2894660 TI - Beta-adrenergic mechanisms during severe myocardial ischemia and evolving infarction. AB - Severe myocardial ischemia and infarction cause release of catecholamines, with exposure of injured myocardial cells to relatively high concentrations during the transitional period in which myocyte injury worsens. In experimental animals, the number of beta-adrenergic receptors increases markedly without any change in affinity within one hour of coronary artery occlusion, and the number of alpha adrenergic receptors also increases. Stimulation by exogenous cate-cholamines during a period of reperfusion one hour after temporary coronary occlusion is associated with an enhanced biochemical response in the ischemic myocardium. Administration of beta-adrenergic blockers prior to or within a few minutes after occlusion limits the extent of myocardial necrosis. In clinical studies, administration of propranolol, timolol, or metoprolol has been shown to significantly reduce the mortality rate after myocardial infarction (MI). Administration of timolol or metoprolol also reduces the frequency of recurrent MI. Beta-adrenergic blockers may prolong life and reduce the risk for recurrent MI by antagonizing and/or preventing basic biologic alterations in injured myocytes and/or by antagonizing detrimental effects of the relatively high concentrations of catecholamines to which these cells are exposed. Increased number of beta-adrenergic receptors, the ability to translate adrenergic stimulation into intracellular metabolic events, and increased local concentrations of catecholamines may be important factors in arrhythmogenesis and myocyte injury during severe myocardial ischemia and evolving MI. PMID- 2894661 TI - Management of hypertension. What is the role of beta blockers? AB - The 1984 report of the Joint National Committee on Detection, Evaluation, and Treatment of Hypertension for the first time recommended beta blockers as an alternative to diuretics for step 1 of stepped-care treatment. Numerous studies have shown that beta blockers are as effective as diuretics for monotherapy in patients with mild hypertension. They are the only antihypertensive drugs that have been shown to be cardioprotective following a myocardial infarction. Beta blockers are especially indicated for step 1 therapy in young patients (particularly those with evidence of hyperkinetic circulation), in patients who have had a myocardial infarction, and in patients with angina, migraine, or hereditary tremor because they are helpful in treating these conditions as well as in managing hypertension. Angiotensin converting enzyme inhibitors and calcium channel blockers are challenging beta blockers and diuretics as the drugs of choice for initial therapy of hypertension in selected patients. Time will ultimately determine the relative roles of each as step 1 therapy. PMID- 2894662 TI - Myocardial cellular alterations during myocardial ischemia and evolving infarction. AB - Primary decreases in oxygen delivery to the myocardium associated with important reductions in coronary blood flow are the main mechanism of myocardial necrosis. Endothelial injury at sites of coronary artery stenosis, platelet attachment, and release of humoral mediators, including thromboxane A2 and serotonin, may be major causes of primary reductions in coronary blood flow leading to unstable angina and acute myocardial infarction (MI). Findings of clinical studies are consistent with the hypothesis that platelet aggregation and subsequent increases in thromboxane and serotonin concentrations may play a role in causing acute MI, death, or both in patients with unstable angina. Animal studies suggest that both thromboxane and serotonin are important in initiating or sustaining the cyclic coronary blood flow reductions that occur after severe stenosis and endothelial injury. If the contribution from either of these humoral mediators is eliminated or antagonized, cyclic flow reductions are usually terminated. Beta blocker and/or thrombolytic therapy administered within the first two hours after onset of coronary artery occlusion may limit infarct size and improve segmental ventricular function. When given within six hours of symptoms of MI, thrombolytic therapy may reduce mortality. PMID- 2894663 TI - Silent myocardial ischemia. Rationale for management. AB - Recent studies show that in many coronary artery disease patients with any form of angina, myocardial infarction, or positive exercise tests but no symptoms, most of the ischemic episodes are silent. Furthermore, evidence is building to suggest that in many patient groups, silent ischemia relates to prognosis. Numerous therapies, including nitroglycerin or isosorbide dinitrate, have been shown to modify silent ischemia and its associated risks. Studies indicate that frequency and perhaps duration of silent ischemic episodes can be modified by treatment with beta-adrenergic blockers or calcium antagonists alone or, even more effectively, with a combination of both types of agent. Many ischemic episodes persist, however, when therapy is directed only at reduction of angina. Evidence suggests that some characteristics of silent ischemia predict prognosis, whereas angina characteristics do not. Until additional data about prognosis and the influence of treatment on prognosis are available, the appropriate focus seems to be improvement of outcome in those patients who are at highest risk, rather than only reduction of chest pain. PMID- 2894664 TI - Beta-blockage therapy and cardiovascular disease. Past, present, and future. AB - The concept of two patterns of catecholamine activity was first described at the turn of the century by Langely and Dale. In the late 1940s, Ahlquist conceptualized the alpha- and beta-blocking actions of catecholamines. Sir James Black's research in the 1950s led to the introduction of pronethalol and then of propranolol into the therapeutics of angina and arrhythmias. Early beta-receptor blocking compounds were noted not only to be competitive inhibitors of the beta receptor but to have a direct depressant, membrane-stabilizing action. Later compounds, such as pindolol, were noted to have partial agonist activity. Practolol, metoprolol, atenolol, and similar "cardioselective", or beta selective, drugs were subsequently described. Agents that combine beta blockade with alpha blockade or vasodilator action have been developed recently. There are various therapeutically advantageous pharmacodynamic differences among the beta blocking drugs, such as less effect of beta 1-selective drugs on bronchial smooth muscle. Lipid solubility, systemic bioavailability, first-pass liver metabolism, renal excretion, and brain penetration are pharmacokinetic properties that further distinguish one agent from another. After the initial predicted therapeutic uses, beta-blocking drugs were used in hypertension and subsequently have been applied in a wide range of cardiovascular conditions. Recent work clearly demonstrating a cardioprotective effect in the post-myocardial infarction period is a major reason that use of the agents is likely to remain high. PMID- 2894665 TI - The secondary prevention trials. Lessons learned, questions raised. AB - In clinical trials to date, only two types of treatment have been shown to have a positive effect on survival in patients after acute myocardial infarction: beta blockers in acute-phase as well as long-term therapy and thrombolytic agents administered within three to four hours of the onset of symptoms. The favorable trial results from these interventions have raised new questions of scientific and clinical significance. What is the mechanism of the favorable action? Do all patients stand to benefit from treatment? What is the optimal time for initiation of treatment? How long is the treatment beneficial? What are the risks and costs? What is the public health impact of widespread use of these interventions? PMID- 2894666 TI - Early intravenous beta blockade in acute myocardial infarction. AB - In the critical period during which ischemia progresses to infarction, beta blocking drugs are known to reduce oxygen demand and prevalence of arrhythmia. To investigate whether this treatment confers clinical benefits, 28 trials have been conducted involving some 27,500 patients during the early hours after onset of symptoms suggesting acute myocardial infarction (MI). Patients were randomized to receive either initial intravenous beta blocker plus oral maintenance or standard therapy. In toto, these trials indicated that early-intervention short-term beta blocker treatment reduces: (1) the risk for early death, reinfarction, and ventricular fibrillation by about 15%; (2) enzymatic indices of infarct size; (3) the number of patients with threatened MI in whom a confirmed MI develops; and (4) the frequency of repetitive and nonrepetitive ventricular arrhythmias. Overall, the treated group had few major side effects other than a small excess of reversible and nonfatal heart block and hypotension. Retrospective analyses suggest (but do not prove) that the reduction in mortality is greatest for those treated within two hours of pain and during the first two days. These results indicate that early initial administration of intravenous beta blocker plus one week's oral beta-blocker treatment produces modest benefits that would presumably be of major public health importance if such treatment were widely used. PMID- 2894667 TI - Modulation of functional capacity and survival in congestive heart failure. Effects of activation of the sympathetic nervous system. AB - Although the sympathetic nervous system is markedly activated in most patients with congestive heart failure, it is not clear whether such activity is clinically beneficial (and should be reinforced) or detrimental (and should be pharmacologically blocked). Some insights pertinent to this important question can be gained by reviewing the results of clinical trials with beta agonists and antagonists. Neither beta 1-selective (prenalterol) nor beta 2-selective (pirbuterol) agonists have been shown to be effective in treating heart failure in double-blind, placebo-controlled studies; moreover, research has indicated that prolonged stimulation of beta receptors with oral or intravenous catecholamines may adversely affect survival. In contrast, sustained therapy with drugs that attenuate the effects of the sympathetic nervous system (by blocking either tyrosine hydroxylase or beta-adrenergic receptors) may produce hemodynamic and clinical improvement and may favorably affect long-term prognosis. These potential benefits of beta-adrenergic blockade contrast strikingly with the lack of efficacy (with respect to clinical status and survival) of agents that block alpha-adrenergic receptors. Beta-adrenergic blockade carries important risks in the patient with heart failure, however. The risk-to-benefit ratio cannot be delineated accurately until the outcome of additional randomized clinical trials is known. PMID- 2894668 TI - [Churg-Strauss syndrome]. PMID- 2894669 TI - [Advancing acromegaly with low growth hormone levels. Influence of an analog of somatostatin administered in continuous subcutaneous infusion]. PMID- 2894670 TI - [Osteocalcin: an index of development of acromegaly?]. PMID- 2894671 TI - [Myorelaxant cutaneous tests]. PMID- 2894672 TI - Neurochemical effects of cyclopiazonic acid in chickens. AB - Chickens dosed (per os) with cyclopiazonic acid (CPA) at 0.5, 5.0, and 10 mg/kg body weight showed significant (P less than or equal to 0.05) increases in brain dopamine and serotonin concentrations 96 hr after dosing. The increases coincide with significant decreases in homovanillic acid and subtle increases of dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid concentrations. The elevated dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid concentrations may be related to the elevated concentrations of dopamine and serotonin, respectively. The observed changes in neurotransmitter/metabolite concentrations 96 hr after dosing parallel elimination of CPA from the birds skeletal muscles; however, they do not correlate with the significant weight losses in these birds at 48 and 96 hr after dosing. The brain weights of the treated birds were statistically insignificant from their respective controls, although increases in brain weight-body weight ratio within treatments and with time correlated with CPA toxicity. No significant changes were observed in dopamine, dihydroxyphenylacetic acid, homovanillic acid, serotonin, and 5 hydroxyindoleacetic acid concentrations among the treatments at 3, 24, and/or 48 hr after dosing. PMID- 2894673 TI - Beta receptors and resistance to phosphaturic effect of PTH in respiratory alkalosis. PMID- 2894674 TI - Effect of dermorphin on body temperature in rats. AB - The effect of dermorphin on regulation of body temperature was studied in the rat under extreme and thermoneutral environmental temperatures and in different nutritional states. Intracerebroventricular (icv) injections of dermorphin at dose levels of 10, 50, 100 ng/rat produced hypothermia in animals placed in cold temperatures (-10 degrees C and +4 degrees C) and hyperthermia at ambient (+22 degrees C) and higher temperatures (+34 degrees C). These data emphasize the importance of using a wide range of environmental temperatures in studying drug effects on thermoregulation. To determine whether the effect of dermorphin on body temperature was related to the nutritional state of the animal, as observed with other neuropeptides (i.e., bombesin, litorin), the thermoregulatory response was followed in fed and fasted rats. The same results were obtained in both experimental groups. In all cases, dermorphin change in body temperature was mediated via an action on typical opioid receptors since it was completely prevented by pretreatment with naloxone. PMID- 2894675 TI - Behavioral responses to psychomotor stimulant drugs: localization in the central nervous system. PMID- 2894676 TI - Dependence as a limiting factor in the clinical use of minor tranquillizers. AB - The recognition that all minor tranquillizers carry the risk of dependence has had a significant impact in their prescription over the years. But it has only recently had the same impact on the prescribing of benzodiazepines because their dependence risks were not recognized until late. Approximately one third of all patients prescribed a benzodiazepine regularly for six weeks or longer will experience withdrawal symptoms if the drug is withdrawn suddenly after this time. Even if the drug is withdrawn gradually withdrawal symptoms may still lead to demands for further prescription. The major change in prescribing has been towards shorter and intermittent treatment so that tolerance is reduced and withdrawal symptoms avoided. This is appropriate for acute anxiety reactions but more difficult for longer term anxious and depressive neurotic disorders, which have a much longer natural history. Continuing evidence that other drugs not specifically marketed for the relief of anxiety, particularly the antidepressants, are effective in relieving this anxiety has led to increased prescription of antidepressants. Some patients may also be helped by treatment with beta-blocking drugs and new agents such as buspirone which have no significant dependence potential. There has also been a move away from drug treatment to psychological treatments for anxiety as a consequence of concern over dependence. For some conditions, particularly medical ones such as spasticity and epilepsy, benzodiazepines may be considered for long-term treatment. They may also be regarded as necessary for more severe psychiatric disorders, usually as an adjunct to other therapy. In such instances the dependence risk is acknowledged but the benefits of treatment are considered to outweigh them. There may also be patients who are dependent on benzodiazepines but the alternative of withdrawing the drug may lead to dependence on a more dangerous drug such as alcohol. In such cases it is reasonable to regard continued prescription of the benzodiazepine as the least dangerous course of action. It is important to maintain a perspective of dependence on minor tranquillizers, particularly as attitudes are in danger of being distorted by excessive media attention. To date there is no evidence that dependence on benzodiazepines leads to any dangerous long term sequelae although there is concern over their effects on higher cognitive function. Nevertheless, the dangers of barbiturates, alcohol and nicotine are so much greater that it would be unfortunate if public concern led to excessive restrictions on the use of benzodiazepines.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2894677 TI - Prokaryotic DNA replication mechanisms. AB - The three different prokaryotic replication systems that have been most extensively studied use the same basic components for moving a DNA replication fork, even though the individual proteins are different and lack extensive amino acid sequence homology. In the T4 bacteriophage system, the components of the DNA replication complex can be grouped into functional classes as follows: DNA polymerase (gene 43 protein), helix-destabilizing protein (gene 32 protein), polymerase accessory proteins (gene 44/62 and 45 proteins), and primosome proteins (gene 41 DNA helicase and gene 61 RNA primase). DNA synthesis in the in vitro system starts by covalent addition onto the 3'OH end at a random nick on a double-stranded DNA template and proceeds to generate a replication fork that moves at about the in vivo rate, and with approximately the in vivo base-pairing fidelity. DNA is synthesized at the fork in a continuous fashion on the leading strand and in a discontinuous fashion on the lagging strand (generating short Okazaki fragments with 5'-linked pppApCpXpYpZ pentaribonucleotide primers). Kinetic studies reveal that the DNA polymerase molecule on the lagging strand stays associated with the fork as it moves. Therefore the DNA template on the lagging strand must be folded so that the stop site for the synthesis of one Okazaki fragment is adjacent to the start site for the next such fragment, allowing the polymerase and other replication proteins on the lagging strand to recycle. PMID- 2894678 TI - Eukaryotic chromosome replication. PMID- 2894679 TI - Mammalian DNA polymerase alpha: a replication-competent holoenzyme form from calf thymus. AB - Calf thymus DNA polymerase alpha, like the replication-specific DNA polymerase III holoenzyme of Escherichia coli, can be isolated as a distinct complex. A specific multiprotein form of the polymerase alpha, a form designated replication competent (RC) holoenzyme, consists of a complex of a polymerase-primase core and at least six other polypeptides. The RC holoenzyme can efficiently replicate several naturally occurring templates, including the genomic DNA of the porcine circovirus (PCV). The DNA of this virion consists of a single-stranded circle with a defined replication origin, and its replication requires the cellular DNA replication machinery. It might therefore provide an invaluable opportunity to investigate chromosomal replication mechanisms, analogous to the way that studies on E. coli bacteriophage DNA replication elucidated host DNA replication mechanisms. Calf RC holoenzyme alpha selectively initiates PCV DNA replication in vitro at a site that possibly represents a consensus sequence of cellular DNA replication origins. The cell-free PCV replication system will be exploited for the in vitro dissection and reconstitution of the RC holoenzyme and the functional analysis of its component polypeptides. PMID- 2894680 TI - Replication of adenovirus and SV40 chromosomes in vitro. AB - As an approach to studying the mechanisms involved in the replication of eukaryotic chromosomes, we have developed and characterized cell-free replication systems for the animal viruses, adenovirus and SV40. In this report we summarize recent work on the proteins required for the initiation of DNA synthesis in these two systems. The adenovirus origin of DNA replication was shown to consist of three functionally distinct sequence domains. Cellular proteins that specifically recognize each of these domains were purified and characterized. Initiation of adenovirus DNA replication was reconstituted from two virus-encoded and three cell-encoded factors. The SV40 origin of replication consists of a 65 base pair DNA segment that contains a high affinity binding site for the viral initiation protein T antigen. Evidence is presented that the first step in initiation of SV40 DNA replication involves the specific binding of T antigen to the origin, followed by the local unwinding of the two strands of the template. The unwinding reaction is specific for DNA templates containing the SV40 origin and requires ATP hydrolysis. In addition to T antigen, efficient unwinding requires a cellular factor(s) that can be replaced by the single-stranded DNA binding protein of Escherichia coli. These results indicate that the recently discovered helicase activity of T antigen plays a central role in initiation of viral DNA synthesis. PMID- 2894681 TI - In vitro replication of DNA containing either the SV40 or the polyoma origin. AB - The replication of DNA containing either the polyoma or SV40 origin has been done in vitro. Each system requires its cognate large-tumour antigen (T antigen) and extracts from cells that support its replication in vivo. The host-cell source of DNA polymerase alpha - primase complex plays an important role in discriminating between polyoma T antigen and SV40 T antigen-dependent replication of their homologous DNA. The SV40 origin- and T antigen-dependent DNA replication has been reconstituted in vitro with purified protein components isolated from HeLa cells. In addition to SV40 T antigen, HeLa DNA polymerase alpha - primase complex, eukaryotic topoisomerase I and a single-strand DNA binding protein from HeLa cells are required. The latter activity, isolated solely by its ability to support SV40 DNA replication, sediments and copurifies with two major protein species of 72 and 76 kDa. Although crude fractions yielded closed circular monomer products, the purified system does not. However, the addition of crude fractions to the purified system resulted in the formation of replicative form I (RFI) products. We have separated the replication reaction with purified components into multiple steps. In an early step, T antigen in conjunction with a eukaryotic topoisomerase (or DNA gyrase) and a DNA binding protein, catalyses the conversion of a circular duplex DNA molecule containing the SV40 origin to a highly underwound covalently closed circle. This reaction requires the action of a helicase activity and the SV40 T antigen preparation contains such an activity. The T antigen associated ability to unwind DNA copurified with other activities intrinsic to T antigen (ability to support replication of SV40 DNA containing the SV40 origin, poly dT-stimulated ATPase activity and DNA helicase). PMID- 2894682 TI - Nuclear gene products that function in mitochondrial DNA replication. AB - Mammalian mitochondrial DNAs replicate unidirectionally from two distinct strand specific origins. A round of replication begins at the heavy-strand origin (the D loop) where transcripts from an upstream promoter serve as the primers for DNA synthesis. The transition from RNA to DNA synthesis occurs within short, conserved nucleotide sequence blocks and is mediated by specific endonucleolytic cleavage of the primary transcript. An enzymic component involved in the generation of primer RNA in mouse mitochondria has been identified. It is a sequence-specific endoribonuclease that cleaves single-stranded RNA substrate precisely at one of the transition sites. The other origin, that for light-strand synthesis, is located well apart on the genome and functions only when in a single-stranded template form. This origin has a defined secondary structure that is the most highly conserved sequence element in mammalian mitochondrial DNAs. Initiation of replication at this origin is by the action of a mitochondrial DNA primase, which is capable of synthesizing a short stretch of ribonucleotides before switching to DNA synthesis. Mitochondrial DNA primase appears to have an associated RNA species and the evidence to date suggests that components of both the D-loop endoribonuclease and the DNA primase are nuclear gene products. PMID- 2894683 TI - Chromosome replication in cell-free systems from Xenopus eggs. AB - Cell-free systems from eggs of the frog Xenopus laevis are able to perform most of the acts of eukaryotic chromosome replication in vitro. This now includes the crucial regulatory step of initiation, which had only been achieved for viral systems previously. Purified DNA or nuclei are able to initiate and complete semi conservation replication in egg extracts in vitro (Blow & Laskey, Cell 47, 557 587 (1986). Replication does not require specialized DNA sequences either in vitro or in microinjected eggs, but in both systems large templates replicate more efficiently than small templates. In some cases replication can re-initiate, excluding the possibility that replication is primed by preexisting primers in the template preparations. When nuclei are replicated in vitro, only one round of replication is observed in a single incubation resembling the single round of replication observed for purified DNA after micro-injection. The mechanism that prevents re-initiation of replication within a single cell cycle is discussed and certain models are eliminated. Nucleosome assembly from histones and DNA has also been studied in cell-free systems from Xenopus eggs. Fractionation has led to the identification of two acidic proteins called nucleoplasmin and N1, which bind histones and transfer them to DNA. The sequences of both proteins have been determined by cDNA cloning and sequencing. Both proteins are found as complexes with histones in eggs. PMID- 2894684 TI - Identification of multiple cellular factors required for SV40 replication in vitro. AB - The replication of simian virus 40 has been studied by using cell-free extracts derived from human 293 cells. Fractionation of this extract has led to the identification of three fractions that are required for efficient DNA synthesis. Initial fractionation of the crude extract by phosphocellulose chromatography has produced two fractions, I and II, neither of which is able to support replication separately, but when they are combined, efficient synthesis is restored. Both fractions are required, with SV40 T antigen, for the formation of a presynthesis complex at the SV40 origin. The major replication enzymes, DNA polymerase, DNA primase and the topoisomerases I and II all reside in fraction II. Fraction I has been subdivided into two subfractions (A and B) by DEAE-cellulose chromatography. Fraction A is essential for replication and is required for presynthesis complex formation. Fraction B stimulates DNA replication and is only required at the elongation stage. This multicomponent system has provided the foundation for identification of individual components that are required for DNA replication in vitro. PMID- 2894685 TI - Control over the onset of DNA synthesis in fission yeast. AB - The fission yeast Schizosaccharomyces pombe has been used to identify gene functions required for the cell to become committed to the mitotic cell cycle and to initiate the processes leading to chromosome replication in S-phase. Two gene functions cdc2 and cdc10 must be executed for the cell to traverse 'start' and proceed from G1 into S-phase. Before the completion of these two functions the cell is in an uncommitted state and can undergo alternative developmental fates such as conjugation. A third gene, suc1, has also been identified whose product may interact directly with that of cdc2 at 'start'. The molecular functions of the genes involved in the completion of 'start' have been investigated. The cdc2 gene has been shown to be a protein kinase, suggesting that phosphorylation may be involved in the control over the transition from G1 into S-phase. The biochemical functions of the cdc10 and suc1 gene products have not yet been elucidated. A control at 'start' has also been shown to exist in the budding yeast Saccharomyces cerevisiae. Traverse of 'start' requires the execution of the CDC28 gene function. The cdc2 and CDC28 gene products (lower-case letters represent genes of Schizosaccharomyces pombe, and capital letters genes of Saccharomyces cerevisiae) are functionally homologous, suggesting that the processes involved in traverse of 'start' are highly conserved. An analogous control may also exist in the G1 period of mammalian cells, suggesting that the 'start' control step, after which cells become committed to the mitotic cell cycle, may have been conserved through evolution. PMID- 2894686 TI - Initiation of DNA replication in yeast chromosomes. AB - A family of DNA fragments from the yeast genome has properties that suggest that chromosome replication starts at specific DNA sequences. These elements (autonomously replicating sequences: ARS) have a bipartite structure: a small (less than 20 base pairs) AT-rich region essential for function, flanked by larger regions important for maximal activity of the replicator. In an attempt to identify proteins involved in initiation of replication, yeast mutants that show an enhanced ability to replicate minichromosomes with defective ARSS have been isolated. PMID- 2894687 TI - Inositol lipids and DNA replication. AB - Control of DNA synthesis by growth factors seems to depend upon the generation of intracellular mitogenic signals, which are responsible for initiating the sequence of events leading to the onset of DNA synthesis. Many growth factors have tyrosine kinase activity suggesting the proteins phosphorylated on tyrosine might be likely candidates as intracellular signals. Other candidates are the calcium and hydrogen ions whose concentrations change dramatically during the action of most growth factors, many of which also stimulate the hydrolysis of inositol lipids. In particular, certain growth factors stimulate the hydrolysis of phosphatidylinositol 4,5-bisphosphate to give the two second messengers diacylglycerol and inositol 1,4,5-trisphosphate (Ins1,4,5P3). The former stimulates protein kinase C, which is responsible for increasing intracellular pH by switching on an Na+-H+ exchanger. The water-soluble Ins1,4,5P3 released to the cytosol can be metabolized along two separate pathways: it can either be dephosphorylated to free inositol or it can be converted into additional inositol polyphosphates such as Ins1,3,4,5P4 and Ins1,3,4P3. These inositol phosphates seem to play a key role in regulating intracellular calcium, with Ins1,4,5P3 functioning to release internal calcium, whereas Ins1,3,4,5P4 may function to regulate the entry of external calcium. There is evidence to suggest that these internal messengers may converge on certain key processes responsible for initiating the programme of cell growth. It is argued that an increase in intracellular calcium might be an important intracellular signal for activating both the transcription of a family of early genes, typified by fos, as well as the enzyme S6 kinase, which phosphorylates the ribosomal protein S6 which may regulate protein synthesis. The increase in pH seems to play a permissive role and may create the necessary ionic milieu for S6 phosphorylation and protein synthesis to occur. The onset of RNA and protein synthesis, which occur within the first few minutes after the arrival of a growth factor, represent the initial events of the programme of cell growth which culminates in DNA synthesis and cell division. PMID- 2894688 TI - The bending of DNA in nucleosomes and its wider implications. AB - The DNA of a nucleosome core particle is wrapped tightly around a histone octamer with approximately 80 base pairs per superhelical turn. Studies of both naturally occurring and reconstituted systems have shown that DNA sequences very often adopt well-defined locations with respect to the octamer. Recent work in this laboratory has provided a structural explanation for this sequence-dependent positioning in terms of the differential flexibility of different sequences and of departures from smooth bending. The 'rules' that are emerging for DNA bendability and, from the results of other workers, on intrinsically bent DNA, are likely to be useful in considering looping and bending of DNA in other processes in which it is thought to be wrapped around a protein core. PMID- 2894689 TI - Relation of chromosome structure and gene expression. AB - We have been able to map specific DNA fragments at the bases of chromatin loops with the help of a novel extraction procedure by using lithium-3',5' diiodosalicylate. One such scaffold-attached region (SAR) is found in the non transcribed spacer in each repeat of the histone gene cluster, on a 657 base pair (b.p.) restriction fragment. Exonuclease III digestion has localized two protein binding domains on the SAR of the histone cluster. Each covers approximately 200 b.p. and they are separated by a nuclease-accessible region of about 100 b.p. These domains are rich in sequences closely related to the topoisomerase II cleavage consensus. We have studied the scaffold association of three developmentally regulated genes of Drosophila melanogaster: alcohol dehydrogenase (Adh), the homoeotic gene fushi tarazu (ftz) and Sgs-4, a gene encoding one of the glue proteins secreted by third-instar larvae. We find regions attached to the nuclear scaffold (SARS) both 5' and 3' of all three genes, defining small domains ranging from 4.5 to 13 kilobases. In the case of Adh, a gene with two promoters, we find two upstream and two downstream SARS. Those 5' of the gene co map with regulatory regions for the adult and the larval transcripts, respectively. For Sgs-4, the 5' SAR covers 866 b.p. immediately upstream of the transcript, and encompasses the 200 b.p. regulatory region defined by two deletion mutants that produce little or no Sgs-4 protein. In ftz the 5' SAR is found 4.8 kilobases upstream of the start of transcription within a 2.5 kilobase element required for a high level of ftz expression in the early embryo. Sequence analysis of five upstream SARS reveals clusters of sequences closely related to the cleavage consensus of topoisomerase II. In addition, they contain multiple copies of two sequence motifs: a specific 10 b.p. A-rich sequence, and another 10 b.p. T-rich stretch. In conclusion, the intimate association of the SAR with the upstream/enhancer elements, the presence of clustered sequences highly homologous to the topoisomerase II cleavage consensus, and the localization of topoisomerase II in the scaffold, suggest a structure-function relation between chromosome organization and gene expression. PMID- 2894690 TI - Blood coagulation and fibrinolysis in hyperthermic rats. AB - Exposure of rats to an environment of +40 degrees C that increases central (rectal) temperature to about 40 degrees C, importantly decrease the number of thrombocytes, the blood coagulation (the Quick time and Howel time) and euglobulin lysis time (ELT). In order to search for the mechanism responsible for coagulability and fibrinolysis we studied the relations of these changes with the sympatheticoadrenergic system and with the adrenal hormonal secretion. Some parameters were thus explored after adrenalectomy and under the influence of a beta-blocking agent, Eraldin. Adrenalectomy moderately reduced these decreasing effects, excepting the ELT. Eraldin has a contrary effect. Adrenalectomy acts by suppressing the corticoid reaction and by diminishing the catecholamineones. Since Eraldin influences coagulation and fibrinolysis in an opposite sense than adrenalectomy, it may be concluded that catecholamines do moderate the effect of heating, inhibiting and not stimulating circulation, as assumed. On the contrary, corticoids (gluco- or mineralo-) contribute to the effect, influencing coagulation in hyperthermia. Both influences are slight, not determinant. Supplementary explorations revealed that repeated daily exposure for 1-2 or 3 weeks, simply in the cages in which hyperthermia was subsequently produced, decreased also the number of thrombocites, the QT and the ELT, especially the last one. The HT was less influenced. It results that these exposures, produced effects similar with hyperthermia. Heating rats after these daily repeated exposures does not influence these already changed parameters. PMID- 2894691 TI - [Hepatotoxic action of furosemide in experimental liver cirrhosis]. PMID- 2894692 TI - Functional heterogeneity of the right and left cerebral neocortex in the modulation of the immune system. AB - The cerebral neocortex is now known to modulate the immune system but this modulation is hemispherically asymmetrical. It was previously reported that large ablation, including the anterior prefrontal part of the left cortex decreased whereas symmetrical right lesions enhanced B and T cell-mediated responses. However, the neocortex is an heterogeneous structure from anatomical and physiological points of view and it could be speculated that different aspects of the immune system could be regulated by various cortical areas. In these experiments, restricted neocortical lesions involving the parieto-occipital lobes were performed in C3H/He mice. Animals with right lesions showed depressed mitogen-induced lymphoproliferation and enhanced antibody production to sheep erythrocytes as compared to that of animals with bilateral lesions. Left lesions appeared not to modify these reactions. Furthermore, the percentage of suppressor/cytotoxic T lymphocytes was depressed more in animals with bilateral lesions as compared to any of the other groups. None of the lesions performed appeared to modify the natural killer cell activity. These results confirm that connections between left and right cortex are involved in the modulation of the immune system and suggest that the immunomodulatory functions of the cortex depend upon the specific regions within the right cortex. PMID- 2894693 TI - [Imaging of the lungs and heart in the diagnosis of Takayasu arteritis]. PMID- 2894694 TI - [Neurochemistry in Alzheimer's disease]. PMID- 2894695 TI - [Survey of drug therapy in schizophrenia in the aged]. PMID- 2894696 TI - [Modern aspects of epilepsy research and its application]. AB - At present most authors agree with the hypothesis that epilepsy is primarily caused by an imbalance of inhibitory and excitatory transmitter systems of CNS in favour of the latter. Epilepsy research focuses more and more on disorders in structures using amino acids as transmitters. There is a world-wide searching for new antiepileptic strategies with an emphasis on a causally guided therapy. Besides possibilities of pharmacological enhancement of GABA-mediated inhibition, e.g. by recently tested GABA prodrugs, highly potent antagonists of transmitter glutamate, acting as anticonvulsant drugs, are expected to gain in significance for clinical practice. PMID- 2894697 TI - [Psychological determinants of the reaction to work conducted in over- and understimulation of the central nervous system]. PMID- 2894699 TI - Tardive psychosis: does it exist? PMID- 2894698 TI - Serotonin does not mediate anxiolytic effects of buspirone in the fear potentiated startle paradigm: comparison with 8-OH-DPAT and ipsapirone. AB - The present study evaluated the role of various neurotransmitter systems in mediating buspirone's blockade of the fear-potentiated startle effect, where acoustic startle amplitude is normally increase in the presence of a light previously paired with a shock. Large lesions of the dorsal and median raphe nuclei or IP injections of the serotonin antagonists cinanserin (10 mg/kg) or cyproheptadine (5 mg/kg) did not alter fear-potentiated startle, nor did these treatments prevent buspirone (5 or 10 mg/kg SC) from blocking fear-potentiated startle. The 5-HT 1A agonist 8-OH-DPAT (2.5-10.0) did not block fear-potentiated startle even at doses that produced a marked "5-HT syndrome". Another 5-HT 1A agonist, ipsapirone (10-20 mg/kg), blocked potentiated startle only at a very high dose (40 mg/kg). p-Chlorophenylalanine and p-chloroamphetamine did not alter fear-potentiated startle. Finally, pretreatment with the benzodiazepine receptor antagonist RO-15-1788 (1 mg/kg); the opiate antagonist naloxone (2 mg/kg) or the alpha 2-adrenergic antagonist yohimbine (5 mg/kg) did not reduce fear-potentiated startle, nor did they prevent buspirone from blocking fear-potentiated startle. Taken together, the data do not support the hypothesis that buspirone's anxiolytic effects are mediated by actions at 5-HT 1A receptors and more generally indicate that serotonergic neurons do not play an important role in fear-potentiated startle. PMID- 2894700 TI - Lymphocyte beta-adrenergic receptor binding in panic disorder. AB - Lymphocyte beta adrenergic receptor binding using [125I]CNP was determined in patients with panic disorder (N = 4) or agoraphobia with panic attacks (N = 17) and age- and sex-matched healthy subjects (N = 22). The patients showed a significantly lower number of beta-adrenergic receptor binding sites and a significantly higher affinity of binding than healthy subjects. A past or present history of major depression in the patients did not alter these findings. These results are consistent with a growing body of knowledge implicating noradrenergic dysfunction in the pathophysiology of panic anxiety. PMID- 2894701 TI - Morphine-like discriminative stimulus effects of opioid peptides: possible modulatory role of D-Ala2-D-Leu5-enkephalin (DADL) and dynorphin A (1-13). AB - The role of the different opioid receptors was studied in rats trained to discriminate SC injections of 3.0 mg/kg morphine from saline by tests for generalization to graded doses of morphine and receptor-selective peptides administered into the lateral cerebral ventricle. Dose-dependent morphine-like stimulus effects were produced over a wide range of doses (0.001-30 micrograms), depending upon ligand and animal, by morphine, by the mu-selective peptides DAGO[D-Ala2-NMePhe4-Gly(ol)-enkephalin] and FK33824[D-Ala2,NMePhe4-Met(O)5-(ol) enkephalin], and by the delta-selective peptide, DADL[D-Ala2,D-Leu5)enkephalin]. The order of relative potency of these substances was: FK33824 greater than DAGO greater than morphine greater than DADL. In contrast, DPLPE[D-Pen2,L Pen5)enkephalin], which has much greater delta receptor selectivity than does DADL, and dynorphin A(1-13) (0.1-10 micrograms), a kappa-receptor agonist, engendered choice responding appropriate for saline. When 1.0 micrograms DADL, a dose lacking morphine-like discriminative effects, was administered concurrently with SC morphine, the stimulus effects of morphine were potentiated. Concurrent administration of 10 micrograms dynorphin A(1-13) and morphine attenuated the stimulus effects of morphine inconsistently. These results support previous findings that mu-opioid receptors are of primary importance in mediating the morphine-like discriminative effects of opioid peptides. They also suggest that morphine-like discriminative effects can be modulated by other types of opioid receptors. PMID- 2894702 TI - Decreasing sensitivity to neuroleptic agents in developing rats; evidence for a pharmacodynamic factor. AB - Developing rats are far more sensitive than adults to the behavioral effects of haloperidol. The present results support the hypothesis that this change may reflect age-related changes in brain responses such as alterations in drug receptor or drug-effector mechanisms. Dose-response studies of catalepsy and ptosis were conducted in male Sprague-Dawley rats aged 30, 56, or 100 days. Resulting dose-effect curves were approximately parallel and showed rightward shifts with highly significant progressive increases of ED50. Similar developmental decreases in drug sensitivity (3-6x) were found following systemic (PO or IP) administration of haloperidol or the phenothiazine neuroleptic perphenazine, which differ markedly in structure, potency, distribution, and metabolism. Age-related decreases in drug sensitivity (3-4x) were also found using intracerebroventricular (ICV) administration of both agents in an attempt to bypass potential "pharmacokinetic" influences. Since the age-dependent decrease in sensitivity to both neuroleptics was found during the rising phase of drug action (1st hour) and ranked: PO greater than IP greater than ICV, some change in absorption and distribution of both drugs may occur in addition to the apparently important maturational decrease in target-organ sensitivity indicated by the responses to direct ICV injection and by the similarity of results obtained with dissimilar agents. PMID- 2894703 TI - Anxiolytic effects of buspirone and gepirone in the fear-potentiated startle paradigm. AB - Fear potentiation of the acoustic startle reflex was produced by eliciting startle responses in the presence of a light that had been previously paired with a shock. Buspirone (0.6-5.0 mg/kg) and gepirone (1.25-10.0 mg/kg), but not their common metabolite, 1-PP (0.5-40 mg/kg), produced a dose-dependent reduction of fear-potentiated startle. These doses of buspirone and gepirone slightly increased baseline startle levels. Reduction of fear-potentiated startle appears to involve supraspinal sites of action, since intraventricular but not intrathecal administration of buspirone (200 micrograms) reduced fear-enhanced startle. Both buspirone and gepirone were highly efficacious in this model compared to other animal tests that are used to study anxiolytic compounds. PMID- 2894704 TI - Potential anxiolytic properties of 8-hydroxy-2-(di-n-propylamino)tetralin, a selective serotonin 1A receptor agonist. AB - The effects of a selective serotonin 1A receptor agonist, 8-hydroxy-2-(di-n propylamino)tetralin (8-OH-DPAT), were studied in two animal models of anxiety. Peripherally injected 8-OH-DPAT in doses ranging from 0.125 to 2.0 mg/kg did not increase black-white transitions (BWT) and black square entries (BSE) in a two compartment exploratory test or punished responding in a test of conditioned suppression of drinking. With 2.0 mg/kg 8-OH-DPAT BSE and unpunished responding were reduced. In an investigation of the drinking time of water-deprived rats, naive or habituated to the test environment, 1.0 and 2.0 mg/kg 8-OH-DPAT increased the drinking time of naive rats but 2.0 mg/kg 8-OH-DPAT reduced that of habituated animals. In animals deprived of water for 48 h or subjected to immobilization stress for 2 h, 1.0 mg/kg 8-OH-DPAT increased BWT and BSE values in the two-compartment exploratory test. Infusions of 5 micrograms/0.5 microliter 8-OH-DPAT in the nucleus raphe medianus increased BWT and BSE values in the exploratory test and punished responding in the test of conditioned suppression of drinking, whereas the same dose of 8-OH-DPAT injected in the nucleus raphe dorsalis had no effect on punished but suppressed unpunished responding. The effects of 8-OH-DPAT are only detectable in the appropriate experimental conditions. When injected systemically, the effects are evident when a state of arousal of the animals contributes to the overall behavioural output. 8-OH-DPAT shows effects comparable to those of established anxiolytics such as benzodiazepines and barbiturates when it is injected in the nucleus raphe medianus, but not in the dorsalis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894706 TI - Measurement of TSH-binding--inhibiting immunoglobulins (TBII) using a radioreceptor-assay (TRAK) in patients with and without thyroid disease. PMID- 2894705 TI - Biological and immunological characterization of ophthalmopathic Ig in Graves' ophthalmopathy. PMID- 2894707 TI - Measurement of thyroid stimulating antibodies (TSAb) using a T3-releasing in vitro bioassay. PMID- 2894708 TI - Detectability of antibodies directed against different thyroid structures by indirect immunofluorescence, with Graves' patients' sera. A prospective study. PMID- 2894709 TI - Follow up of Graves' patients thyroid stimulating antibody activity during treatment. A prospective study. PMID- 2894710 TI - [T lymphocytes subpopulations determined by monoclonal antibodies in a pediatric population: variable dependent on age]. PMID- 2894711 TI - [Asthma and synthetic antihistaminics]. AB - Anti-histamines are considered weakly effective in the treatment of asthma whether in acute exacerbations or as basic therapy. However, there are numerous arguments which plead in their favour, and not only the recognised role of histamines as an important mediator of the immediate response. Besides, since 1948 when it was shown that the first anti-histamines (classical anti-histamines) possessed undeniable anti-histamine like actions, which showed them to have both broncho-dilator activity and a protective effect on bronchospasm induced by inhalation of histamine or allergens. Unfortunately, this efficacy in asthma is only achieved with high doses which are responsible for troublesome side-effects. This is why with the arrival of new anti-histamines specific for H1 receptors, without anti-cholinergic or sedative effects, one can envisage the day when high dose anti-histamines are evaluated in the treatment of asthma. Pharmacological studies in animals have clearly shown their bronchomotor action. Similarly, the first work carried out in men, confirms the anti-asthmatic potential by showing a protective action in the bronchial response, to isocapnic hyperventilation, to exercise and to allergens. As for anti-H2, their impact on asthmatic broncho constriction is poorly defined: for some they potentiate, for others they inhibit. PMID- 2894712 TI - Influence of somatostatin and epidermal growth factor (EGF) on the proliferation of follicular cells in the organ-cultured rat thyroid. AB - The effects of somatostatin (SS), epidermal growth factor (EGF), as well as interactions among SS, EGF, and TSH in their action on the proliferation of thyroid follicular cells (TFC) in organ culture were investigated. It was shown that (1) SS (10(-7) M) decreased significantly the mean mitotic activity rate (MMAR) of TFC; (2) SS (10(-7) M) suppressed the mitogenic TSH action on the TFC proliferation; and (3) TSH, as well as EGF, caused an elevation of MMARs of TFC, the effect of TSH, however, being much stronger than that of EGF. The acquired data suggest that SS, most probably by paracrine interaction, may inhibit the mitotic activity of TFC. The mitogenic effect of EGF, a potent mitogen for TFC in cell culture, is not so strongly expressed in organ culture. PMID- 2894713 TI - [Almitrine dimesylate (vectarion)--the first representative of a new group of "synergetic" drugs--and its use in pulmonary pathology]. PMID- 2894714 TI - Isoenzyme patterns of Entamoeba histolytica isolated from homosexual men. AB - This is a preliminary report on isoenzyme patterns of Entamoeba histolytica which were examined by starch gel electrophoresis. By this means the amoebae isolated from 17 asymptomatic male homosexuals were characterized into zymodemes. No amoebic strain isolated corresponded to a pathogenic zymodeme. PMID- 2894715 TI - Imipenem/cilastatin as monotherapy in severe infections: comparison with cefotaxime in combination with metronidazole and cloxacillin. Report from a Norwegian Study Group. AB - In a randomised and coordinated multicentre study, 143 patients with severe infections received treatment with either imipenem/cilastatin (72; I/C group) or cefotaxime combined with metronidazole and optional cloxacillin (71; CX/M/CL group). 67 patients in the I/C group and 65 in the CX/M/CL group were evaluable for clinical efficacy. 35 (I/C) and 44 (CX/M/CL) patients had bacteriologically documented infections. The clinical cure rate was 91% for I/C and 94% for CX/M/CL, and the bacteriological efficacy (eradicated strains) was 86% and 81%, respectively. Local reactions (phlebitis) were frequent in each group (I/C 18% and CX/M/CL 25%). Clinical side effects other than phlebitis (I/C 17% vs. CX/M/CL 13%) were mostly mild. Diarrhoea did not occur in I/C group. Laboratory untoward effects were mild and infrequent in each group. Reinfections of the urinary tract and superinfections at all sites prevailed in the CX/M/CL group (9 vs. 6 and 6 vs. 2, respectively). The superinfections were mostly mild. The efficacy and safety of I/C in severe infections were comparable to those of CX/M/CL. PMID- 2894716 TI - Drug therapy in hypertension. Changing trends over the last fifteen years. PMID- 2894717 TI - Crush syndrome following sedative-hypnotic overdosage. PMID- 2894718 TI - Intraspinal narcotic analgesia. Pain management in the failed laminectomy syndrome. PMID- 2894719 TI - The embryonic and adult mouse U1 snRNA genes map to different chromosomal loci. AB - The linkage relationships of mouse adult (mU1a) and embryonic (mU1b) U1 snRNA genes were determined by analysis of the strain distribution patterns of two polymorphic variant RNAs, mU1a2 and mU1b3, in several recombinant inbred strain systems. The locus for mU1b3 RNA maps to the U1 gene cluster, Rnu1b, located near the center of chromosome 3, whereas the locus for mU1a2 RNA, Rnu1a2, is located in the proximal region of chromosome 12, tightly linked to D12-1. Moreover, the lack of linkage between Rnu1a2 and the locus for mU1a1 genes on chromosome 11 demonstrates that the mouse genome contains at least three clusters of U1 snRNA genes. PMID- 2894720 TI - [Pulmonary toxicity of drugs]. PMID- 2894721 TI - [The role of pharmacogenetic factors in the incidence of undesirable effects of drugs]. PMID- 2894722 TI - Tobanum treatment in mild and medium severity hypertension. PMID- 2894723 TI - [In vivo P-31 NMR spectroscopy study of muscle metabolism in disease and under the influence of drugs]. PMID- 2894724 TI - [Demonstration in healthy volunteers of the partial agonist effect of a cardioselective beta-blocker, cicloprolol]. PMID- 2894725 TI - [Use of the Reflotron system for laboratory diagnosis in swine and sheep]. AB - The "Reflotron" system (Boehringer Mannheim) was compared with standard laboratory methods for determination of blood values, e.g. haemoglobin, glucose, urea, ASAT/GOT and GGT in pigs and sheep. Various different commercial control sera as well as blood and plasma samples from pigs and sheep were used for evaluation of its precision. The day-to-day precision of all parameters was satisfactory. The accuracy of the values was tested in 56(48) blood samples of healthy and sick pigs (sheep) by using standard substances (glucose, urea) and by comparing them with values measured by standard laboratory methods. There were systematic differences between "Reflotron" and other values in the glucose- and enzyme-values, which can be corrected with the help of conversion factors. In pigs, the enzyme GGT can not be determined accurately with the "Reflotron" system. PMID- 2894726 TI - Human fatality due to ingestion of the crab Demania reynaudii that contained a palytoxin-like toxin. AB - Clinical accounts of a human fatality resulting from ingestion of the crab Demania reynaudii are documented. The causative toxin was suggested to be palytoxin on the basis of dose-death time relationships and chromatographic properties. PMID- 2894727 TI - A DNA-RFLP typing system that positively identifies serologically well-defined and ill-defined HLA-DR and DQ alleles, including DRw10. AB - A single enzyme/multiple probe system of HLA-DR and DQ typing using restriction fragment-length polymorphism (RFLP) analysis is presented. TaqI-digested genomic DNAs are hybridized sequentially with short DR beta, DQ beta, and DQ alpha cDNA probes. The DR beta probe discriminates between the DR allelic specificities DR1 to DRw14, with the two exceptions of some DR3/DRw13 and some DR7/DRw9 combinations. We describe the positive identification of a DRw10-specific RFLP and demonstrate its segregation in families. The DQ beta probe defines an allelic system that identifies the alleles DQw1, DQw2, and DQw3. This permits the resolution of DR3/DRw13 and DR7/DRw9 alleles by defining the DR/DQ association caused by linkage disequilibrium. The DQ alpha probe defines another allelic series interrelated with, but independent from, the DQ beta series. Specific DQ beta/DQ alpha RFLP combinations correlate with known Dw splits of DR2, DRw6, and DR7. Combined use of the three probes permits the identification of HLA-DR, DQ, and certain Dw specificities and provides an effective and easily interpretable system for major histocompatibility complex class II allogenotyping. PMID- 2894728 TI - The necessity of both allogeneic antigens and stem cells for cyclophosphamide induced skin allograft tolerance in mice. PMID- 2894729 TI - [Long-term anesthesia in injuries of the foot and ankle joint]. PMID- 2894731 TI - DNA polymorphisms of the insulin receptor gene and non-insulin-dependent diabetes mellitus. PMID- 2894730 TI - [Additional oral therapy of atopic dermatitis with unsaturated fatty acids]. AB - The effects of unsaturated fatty acids were examined in a double-blind study on 34 patients suffering from atopic dermatitis. In comparison to the placebo group a clinical improvement (24%) was seen after a three month period during which patients had received linoleic acid and gamma-linolenic acid. PMID- 2894733 TI - [Experimental principles of stem cell transplantation]. PMID- 2894732 TI - [Drug-induced diabetes]. PMID- 2894734 TI - Recent studies in T lymphocyte activation. PMID- 2894735 TI - Neuroendocrine-immune interactions: immunoregulatory signals mediated by neurohumoral agents. AB - While we generally think of the brain and nervous system as central to most basic life processes, the concept of immune regulation or modulation is a relatively new idea. The novelty of such an association may be rooted in classic concepts of neurologic function describing direct innervation of controlled tissues and stimulation across synapses. The involvement of the neuroendocrine system in the precise control of metabolic and a variety of cellular functions should preface its involvement in defense against and/or surveillance for aberrant cell replication. Moreover, a principal characteristic of any control mechanism is feedback from the affected system (be it an organ or single cell). In this framework, it is not unreasonable to expect bidirectional interactions between the nervous and immune systems. Direct innervation of lymphoid tissues was described a number of years ago. More recently, immunoregulatory function has been demonstrated in vitro with a variety of neuroendocrine molecules such as the biogenic amines, SP, CGRP, SOM, vasopressin, ACTH, the endorphins, enkephalins, neurotensin, NGF and VIP. Now it has been shown that many of these same or similar neuroregulatory molecules are produced by cells of the immune system. The possibility that neurotransmitters or peptides, or both, may play a role in vivo in the maintenance of immunocompetence is supported by the finding that specific receptors for the neurohumoral modulators are present on the surface of immunocompetent cells. Current hypotheses speculate that feedback control mechanisms are manifested through the production of lymphokines, PGs and leukotrienes. Though it has not been possible to clearly demonstrate the reciprocal interaction between the neuroendocrine and immune systems in vivo, the evidence to date points to its inevitability. PMID- 2894736 TI - [Behavioural effects of 8-OH-DPAT, a 5-HT1A agonist in rats and effects on the behaviour of antimanic drugs]. AB - Effects of lithium, carbamazepine, zotepine, and clonazepam were examined on the behaviour mediated by 5-HT1A receptor and at 5-HT1A binding sites in rats. Forepaw treading, one component of 5-HT behavioural syndrome following subcutaneous injections of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), was not altered by reserpine, p-chlorophenylalanine, or alpha-methyl-p-tyrosine; in reserpine-treated rats, it was antagonized only by spiperone or by (-) propranolol. These results indicate that 8-OH-DPAT-induced forepaw treading is produced by the direct stimulation of 5-HT1A receptor postsynaptically and also that this behaviour is not mediated by monoaminergic neurons. Lithium, carbamazepine, and zotepine inhibited forepaw treading in untreated rats; only lithium and clonazepam inhibited it in reserpine-treated rats. After 14 days treatment, only lithium enhanced it while its enhancement was abolished by reserpine. Radioligand binding studies using [3H]-8-OH-DPAT demonstrated that zotepine possessed weak affinity for 5-HT1A receptor; others lacked affinity. These results from acute experiments suggest that all drugs tested have inhibitory effects on the 5-HT1A receptor function. These effects, however, were not mediated by 5-HT1A receptor. And it is also suggested that the 5-HT1A receptor function after chronic lithium treatment might be enhanced by monoaminergic systems transsynaptically. PMID- 2894737 TI - Effect of high carbohydrate diet on serum gamma-glutamyl transpeptidase fraction pattern in Japanese young men. AB - Changes in the activity of serum gamma-glutamyl transpeptidase (gamma-GTP) and the percentage of the gamma-GTP fraction in healthy young men given a high carbohydrate diet (480-636 g/day, 80% of the total energy) for 21 days were examined. Serum total gamma-GTP activity showed no significant change in four healthy young volunteers who received high carbohydrate diet for 21 days. However, the percentage of the gamma-GTP (1) fraction increased significantly (P less than 0.01) from the basal level of 55.6 +/- 4.0% to 67.6 +/- 0.9% on day 10, and then decreased to 58.4 +/- 1.4% on day 21. When the experimental diet was replaced by usual diet, the percentage of the gamma-GTP (1) fraction returned to the same level as before the experiment. It is concluded from the results that the nutrient intake affects the percentage of gamma-GTP (1), but not the total serum gamma-GTP activity. PMID- 2894739 TI - Efficacy of 0.3 mg morphine intrathecally in preventing tourniquet pain during spinal anaesthesia with hyperbaric bupivacaine. AB - Tourniquet-induced pain is probably mediated by C-fibres. The ability of morphine to interrupt this nociceptive conduction was studied in a double-blind fashion by administering either morphine 0.3 mg or saline intrathecally along with hyperbaric bupivacaine 15 mg for spinal anaesthesia in 40 patients undergoing orthopaedic surgery on the lower extremity. The block characteristics were similar in both groups. During surgery, no patient in the morphine group complained of pain, whereas in the saline group one patient complained of pain caused by the tourniquet and two other patients experienced surgical pain. A 60 min experimental thigh tourniquet pressure provocation (53 kPa for 20 min; 0 kPa for 20 min; 53 kPa for 20 min) on the contralateral unoperated extremity was then performed following surgery, when the spread cephalad of the sensory block had decreased below the T10 dermatomal level. Eight patients in the morphine group experienced no pain in this test, compared with two patients in the saline group (P less than 0.05). The remaining 12 patients in the morphine group had pain responses similar to those patients not given morphine. Intrathecal morphine provides a level of prophylaxis against tourniquet pain. However, the dosage employed here was associated with urinary and emetic side-effects. PMID- 2894738 TI - Cytochemical evaluation of gamma-glutamyl-transpeptidase activity in cervical smears. AB - The cervicovaginal smears of 43 patients attending an outpatient service for early cancer detection were cytochemically studied for the presence of gamma glutamyl-transpeptidase (GGT) in epithelial cells. This was done in order to evaluate such an enzyme phenotype as a marker for cancer development. The results showed that 70% of the 38 patients with a cytologic diagnosis of "inflammatory" or preneoplastic/neoplastic conditions had GGT-positive cells in their smears. None of the five cytologically normal cases showed any epithelial cells with GGT activity. Although most of the GGT-positive cells were metaplastic, some morphologically normal, dysplastic or neoplastic cells also expressed the enzyme. The data suggest that cytochemically detectable transpeptidase activity appears whenever alterations of the normal epithelial microenvironment occurs, but is not necessarily linked to the carcinogenic process. Therefore, cytochemically GGT positive cells should not be used as an indicator of neoplastic transformation of the cervical epithelium. PMID- 2894740 TI - The site of action of trimethaphan-induced neuromuscular blockade in isolated rat and frog muscle. AB - The present study was undertaken to determine the site of action of trimethaphan in causing neuromuscular blockade using isolated rat and frog muscle. Trimethaphan and d-tubocurarine attenuated the twitch tension developed by nerve stimulation, trimethaphan being 1/100 to 1/200 as potent as d-tubocurarine. Neostigmine potentiated the inhibitory effect of trimethaphan but reversed the effect of d-tubocurarine. Trimethaphan shifted the dose response curve of frog rectus abdominis muscle for carbachol downwards, while d-tubocurarine shifted the curve parallel to the right. Treatment with d-tubocurarine or succinylcholine protected acetylcholine receptors from persistent blockade by alpha-bungarotoxin while, in contrast, trimethaphan failed to protect the receptors. The findings indicate that trimethaphan acts on the motor endplate but, unlike d-tubocurarine, does not interact with the recognition site of acetylcholine receptors; the action of trimethaphan appears to be associated with the blockade of endplate ionic channels. PMID- 2894741 TI - Experience of multiple supplementary doses of vecuronium. Case report. AB - Seventy-one supplementary doses of vecuronium were used for muscle relaxation during a 22-h-long NLA II anaesthesia. For assessment of neuromuscular blockade, train-of-four stimulation was used to measure the twitch force of the adductor pollicis after electrical stimulation of the ulnar nerve. No cumulative effect of vecuronium could be demonstrated, measured under strictly controlled conditions. Adding isoflurane 0.5% (end tidal) only slightly prolonged the neuromuscular blocking effect. PMID- 2894743 TI - Electrogenic and electroneutral components of the sympathetic effect on fluid absorption in the rat jejunum. AB - The aim of the study was to test the hypothesis that the sympathetic nerves to the jejunum enhance net fluid absorption rate by inhibiting an electrogenic flux of anions into the lumen. The design of the experiments was based on the observation that the effect of catecholamines on electrogenic transport is abolished by yohimbine, an alpha 2 adrenergic antagonist. Net electrogenic transport in jejunal segments of anaesthetized rats was estimated by measurement of the transepithelial potential difference (PD) and short-circuit current (SCC). Net fluid absorption rate was quantified by a gravimetric technique. The sympathetic nerves to the segment were stimulated electrically, both in vitro and in vivo. The effect of sympathetic nerve stimulation on SCC and net fluid transport was determined in the absence and presence of the alpha-adrenergic antagonists phentolamine (a non-selective alpha-adrenergic antagonist), prazosin (a selective alpha 1-antagonist) and yohimbine (a selective alpha 2-antagonist). Sympathetic nerve stimulation decreased PD and SCC and increased net fluid absorption rate. Phentolamine abolished both the electrogenic response and the effect on net fluid absorption rate, without having any significant intrinsic effects on either parameter. Prazosin per se markedly increased net fluid absorption rate, but did not significantly influence the sympathetic effect on SCC or net fluid absorption rate. Yohimbine abolished the electrogenic effect of sympathetic stimulation, and per se increased net fluid absorption rate in innervated but not in denervated segments. In innervated segments, the absorption rate during sympathetic nerve stimulation was similar in controls and yohimbine treated animals. In denervated segments, yohimbine significantly attenuated the sympathetic response. The results suggest that the sympathetic nerves enhance fluid absorption rate via effects on both electrogenic and electroneutral epithelial transport. These two components of the sympathetic response seem to be mediated by different alpha-receptor mechanisms. PMID- 2894742 TI - Alpha-adrenoceptor stimulation, but not muscarinic stimulation, increases cyclic AMP accumulation in brain slices due to protein kinase C mediated enhancement of adenosine receptor effects. AB - In the present study, using rat hippocampal slices, we have further examined the stimulatory effect of alpha 1-adrenoceptors on the accumulation of cyclic AMP, which is known to depend on calcium and adenosine. The addition of noradrenaline (NA) stimulated the accumulation of [3H]inositol phosphates in [3H]inositol treated slices. This effect was shared by carbachol (10-100 mumol l-1) but not by the adenosine receptor agonist 2-chloroadenosine (100 mumol l-1). The stimulatory effect of the alpha-agonists (phenylephrine or NA + propranolol) on cyclic AMP was shared by a diacylglycerol derivative, sn-1-oleyl-2-acetyl glycerol (OAG), and by the tumour-promoting phorbol esters phorboldibutyrate (PDiBu) and tetradecanoyl phorbol acetate (TPA). PDiBu caused a translocation of protein kinase C from soluble to particulate fractions. The effects of PDiBu and alpha adrenoceptor stimulation on cyclic AMP were not additive. Surprisingly, carbachol (1-1000 mumol l-1) did not stimulate cyclic AMP accumulation in rat hippocampal slices either in the presence or in the absence of an adenosine receptor agonist. The results are compatible with the opinion that alpha-adrenoceptor stimulating drugs enhance the formation of inositol phosphates and diacylglycerol, which synergistically activate protein kinase C, which in turn augments the stimulation of cyclic AMP formation. Thus, a neurotransmitter whose principal biological effect is to stimulate inositol phosphate formation can influence cyclic AMP formation by virtue of an interaction with the actions of the ubiquitous neuromodulator adenosine. The fact that the effect of the alpha-receptor stimulation was not mimicked by a muscarinic agonist could indicate that other factors besides activation of inositol phospholipid hydrolys are important for this receptor-receptor interaction. PMID- 2894744 TI - Enteric nerves mediate the fluid secretory response due to Salmonella typhimurium R5 infection in the rat small intestine. AB - Eighteen hours after intragastric inoculation Salmonella typhimurium elicited a net fluid secretion in the jejunum and ileum of rats. The mechanisms behind the secretory response were analysed in vivo. Extrinsic denervation of the experimental intestinal segments had no effect. The nerve-blocking agents hexamethonium (i.v.) and lidocaine (serosally applied) blocked the secretion but atropine had no effect. It was demonstrated that the bacteria were invasive by culturing from the intestinal wall. The presence of inflammatory reactions was supported by the facts that i.v. indomethacin blocked the secretory response and that there was an increased capillary leakage of albumin-bound Evans Blue into the interstitium of the intestinal mucosa. There was also a secretory response upon inoculation of the jejunal and ileal segments by cell-free supernatants of broth where bacteria had been cultured for 24 h and thereafter lysed. This response was, however, blocked by i.v. atropine, which had no effect on the secretion elicited by living bacteria. We could show no presence of E. coli LT, ST or cholera toxin in the cell-free supernatant by means of ELISA-tests. We therefore conclude that (1) S. typhimurium R5 invaded the rat jejunal and ileal mucosa, thereby creating an inflammatory response which in turn activated a nerve reflex(es) within the ENS leading to a net fluid secretion; (2) the presence of prostaglandins was needed for activating the reflex(es); (3) the reflex(es) contained a nicotinergic transmission; (4) enterotoxin was of no importance for the secretory response in the model used. PMID- 2894745 TI - Severe akathisia causing neuroleptic failure: an indication for lithium therapy in schizophrenia? AB - Several neuroleptics recurrently failed to ameliorate psychosis in three schizophrenic patients. Failures were caused by recurrent intractable akathisia, unresponsive to diazepam and trihexyphenidyl. Lacking this extrapyramidal side effect, lithium carbonate was tried and proved an effective antipsychotic. It is suggested that in schizophrenic psychosis lithium is a rational therapeutic option in cases of neuroleptic intolerance and failures due to akathisia. PMID- 2894746 TI - Clinical symptomatology and drug compliance in schizophrenic patients. AB - The differences in the psychopathologic status of 26 complaint and 32 noncomplaint schizophrenic patients were evaluated on the basis of rating scales used at discharge. Noncomplaint patients had significantly higher scores for grandiosity, lack of feeling of illness and insight into it. Their score for global psychopathological state and disturbance in social adjustment was also significantly higher. The compliant patients had significantly higher score for self-rated depression. PMID- 2894747 TI - A new water-soluble, selective beta-blocker with intrinsic sympathomimetic activity (ICI 141.292) in angina pectoris. AB - In a placebo-controlled, randomized double-blind study the effect of ICI 141.292 (beta 1-selective beta-blocker with intrinsic sympathomimetic activity = ISA) was studied in 11 patients with severe angina pectoris. The doses used were 100, 200 and 300 mg once daily. The 24-hour heart rate was significantly reduced by all regimens, and the Holter-monitoring pattern indicated the presence of ISA-effect at least 20 hours after the 300-mg dose. Maximal heart rate and blood pressure were significantly reduced and exercise duration increased during a symptom limited bicycle exercise test on 200 and 300 mg, but not on 100 mg daily. Resting heart rate and blood pressure were uninfluenced on all regimens. ICI 141.292 is an effective agent in patients with severe angina pectoris. The response pattern suggests the presence of clinically relevant ISA. PMID- 2894748 TI - Comparison between different methods of detecting patients with excessive consumption of alcohol. AB - A study of excessive alcohol consumption was carried out on 2,114 adult somatic outpatients. All patients were evaluated by the following methods: Blood-chemical tests (serum gamma-glutamyltransferase (S-GT), serum aspartate aminotransferase (S-ASAT) and ethanol), patient's and doctor's questionnaires, and analysis of data from psychiatric records, social welfare registers and alcohol ambulatory services. Records from psychiatric clinics detected 48% of the patients. Forty per cent of the alcohol patients had S-GT levels greater than 0.9 mu kat/l. S ASAT and blood ethanol levels were of little informative value. The doctors recognized excessive consumption (greater than 280 g of ethanol/week). The combination of S-GT and questionnaires to patients and doctors detected 63% of the alcohol patients. Both in epidemiological studies and in clinical practice it seems appropriate to use combinations of different methods to detect patients with underlying alcohol problems. PMID- 2894749 TI - Selective beta 1-adrenoceptor blockade and muscle thermogenesis. AB - Muscle thermogenesis was measured by direct microcalorimetry in hypertensive patients randomly treated with either metoprolol or placebo. Samples from rectus abdominis were taken after muscle relaxation during surgery, which was accompanied by a significant increase in arterial plasma noradrenaline. Thermogenesis was significantly lower in the metoprolol group compared with both the hypertensives given (p less than 0.05), and a normotensive group without treatment (p less than 0.005). Metoprolol also provoked a significant fall in body temperature in comparison with the two other groups (p less than 0.01). In the hypertensives given placebo, heat production was inversely related to plasma adrenaline (r = -0.89), indicating a role of the sympatho-adrenal system in muscle thermogenesis. No such correlation appeared during metoprolol treatment. In the present acute stress situation it is suggested that muscle thermogenesis was decreased indirectly by metoprolol via blockade of beta 1-receptors in adipose tissue, causing a relative inhibition of lipolysis with diminished substrate supply to the muscles. PMID- 2894750 TI - Studies of insulin resistance following hypoglycemia in insulin-dependent diabetes mellitus. AB - Insulin resistance was assessed after a hypoglycemia induced by insulin (1.5 mU X kg-1 X min-1) between 7 and 8 a.m. in 10 well-insulinized patients with insulin dependent diabetes mellitus (IDDM). Blood glucose levels during a somatostatin (100 micrograms X h-1)-insulin (0.4 mU X kg-1 X min-1)-glucose (4.5 mg X kg-1) infusion test (SIGIT) performed between 11 a.m. and 3 p.m. served as an indicator of total body insulin resistance. Plasma epinephrine, growth hormone, and cortisol increased in response to hypoglycemia, while blunted responses of glucagon were simultaneously registered. At the start of the subsequent SIGIT, blood glucose and plasma-free insulin concentrations were similar to those obtained in the control study without preceding hypoglycemia, and at this point all counter-regulatory hormones had returned to basal. During the SIGIT close to identical levels of plasma-free insulin and counter-regulatory hormones were registered, despite which a significant hyperglycemia was seen 2 hours after the start of the SIGIT when preceded by hypoglycemia. In a separate study, the SIGIT was shown to have a good reproducibility in IDDM patients. We conclude that hypoglycemia evokes a state of insulin resistance for several hours, as demonstrated by elevated blood glucose levels during a somatostatin-insulin glucose-infusion test. PMID- 2894751 TI - Importance of growth hormone for blood glucose regulation following insulin induced nocturnal hypoglycemia in insulin-dependent diabetes mellitus. AB - The effect of growth hormone (GH) on the glucose homeostasis following nocturnal hypoglycemia was studied between 4 a.m. and noon in eight male patients with insulin-dependent diabetes mellitus (IDDM) by a somatostatin (250 micrograms/h) insulin (0.4 mU/kg/min)-glucose (6 mg/kg/min)-infusion test (SIGIT). The patients participated in two experiments in which hypoglycemia at 4 a.m. was induced by i.v. insulin (1.5 mU/kg/min). In both experiments the endogenous secretion of GH was suppressed by somatostatin (250 micrograms/h) and glucagon (0.5 ng/kg/min) was given as substitute for the somatostatin-induced suppression of endogenous glucagon secretion. GH (20 mU/kg/h) or saline was given for 60 min from nadir blood glucose in random order. Mean nadir glucose values were the same in both studies (1.7 +/- 0.2 vs. 1.7 +/- 0.1 mmol/l) and no differences were registered in plasma-free insulin, glucagon and the responses of adrenaline and cortisol to hypoglycemia. The infusion of GH resulted in plasma GH levels of about 50 micrograms/l at the end of the infusion, thereafter decreasing to low or immeasurable levels within 2 hours. Infusion of GH evoked a marked hyperglycemia within 4 hours. It is concluded that when hypoglycemia is accompanied by a transient increase in plasma GH, insulin resistance occurs after a lag period of approximately 4 hours and that this effect persists for at least another 4 hours. PMID- 2894752 TI - [The physiological effects of beta-adrenergic receptor stimulant on the rabbit lacrimal gland]. PMID- 2894753 TI - Mammogram interpretation by physician assistants. PMID- 2894754 TI - Rheumatoid arthritis: a pharmacologic overview. AB - Numerous drugs are available for the treatment of rheumatoid arthritis. The nonsteroidal anti-inflammatory drugs differ in structure and pharmacokinetics, and they rarely act synergistically. The disease-modifying antirheumatic drugs include gold compounds, penicillamine, hydroxychloroquine and sulfasalazine. Useful immunosuppressive and cytotoxic agents include methotrexate, azathioprine and cyclophosphamide. Costicosteroids find their greatest use in short courses. PMID- 2894755 TI - Frequent alterations of visual pigment genes in adrenoleukodystrophy. AB - Both adrenoleukodystrophy (ALD) and red/green color blindness have been mapped to the distal long arm of the human X chromosome (Xq28). Color-vision defects are frequently associated with ALD, and study of the red and green visual pigment genes in eight ALD kindreds has shown frequent structural changes including deletions and possible intragenic recombinations. Such changes may reflect chromosomal events underlying both ALD and the associated visual defects and should help define both the structural gene responsible for ALD and physical genetic relationships in the Xq28 region. PMID- 2894756 TI - A new peroxisomal disorder with enlarged peroxisomes and a specific deficiency of acyl-CoA oxidase (pseudo-neonatal adrenoleukodystrophy). AB - In the present paper two siblings are presented with clinical manifestations very similar to those of patients affected by neonatal adrenoleukodystrophy. In contrast to neonatal adrenoleukodystrophy patients, hepatic peroxisomes in these siblings were enlarged in size and not decreased in number. Accumulation of very long-chain fatty acids (VLCFA) was associated with an isolated deficiency of the fatty acyl-CoA oxidase, the enzyme that catalyzes the first step of the peroxisomal beta-oxidation. Plasma levels of di- and trihydroxy-coprostanoic acid, phytanic acid, and pipecolic acid were normal; furthermore, acyl CoA:dihydroxyacetone phosphate acyltransferase activity in cultured fibroblasts was also found to be normal. The clinical, biochemical, and cytochemical features found in these two siblings are compared with those seen in two other disorders characterized by the absence of a decreased number of hepatic peroxisomes and the presence of VLCFA: (1) pseudo-Zellweger syndrome (deficiency of peroxisomal thiolase activity) and (2) X-linked childhood adrenoleukodystrophy (deficiency of activation of lignoceric acid). Review of the different biochemical defects possible in very-long-chain fatty-acid oxidation reveals different clinical pictures of varying severity, depending on the level at which the biochemical defect occurs. PMID- 2894757 TI - Analysis of genetic variation reveals human immunoglobulin VH-region gene organization. AB - We have investigated the extent of genetic variation and the number of germ-line heavy-chain-variable (VH) genes to obtain information on the organization and repertoire of the VH genes. Our studies revealed extensive genetic variation in this region, indicated by restriction-endonuclease site polymorphisms. Analysis of the distribution of selected polymorphic loci revealed evidence of linkage disequilibrium, particularly between VH2 and VH3 subclass loci, indicating that the subclasses are interdispersed in the human germ-line chromosome. Absolute correlation was detected between alleles of a VH2 locus and the alleles of three VH3 loci, evidence for an extra set of VH genes, which are present in 48% of the Caucasian population. A preliminary estimate of the number of VH genes, approximately 50, indicates a smaller number of VH genes than suggested by the amount of protein variation. The extensive genetic variation we have observed may be associated with genetic differences in the immune response and potentially with variable susceptibility to autoimmune disorders. PMID- 2894758 TI - DNA polymorphisms of the apolipoprotein AII and AI-CIII-AIV genes: a study in men selected for differences in high-density-lipoprotein cholesterol concentration. AB - We have investigated the frequencies of RFLPs of the apolipoprotein (apo) AII gene and of the apo AI-CIII-AIV gene cluster in 109 men, selected from a random sample of 1,910 men aged 45-59 years, to cover a wide range of plasma high density-lipoprotein (HDL)-cholesterol concentration. There was no significant difference in apo AI or apo AII RFLP allele frequency between groups of individuals with high and low HDL-cholesterol concentration. However, the apo AI PstI RFLP showed an association with genetic variation determining the plasma concentration of apo AI in this sample. Genetic variation in the apo AI-CIII-AIV gene region, as defined by haplotypes, accounted for 16% of the phenotypic variance in the apo AI concentration and for 8% of the phenotypic variance in HDL cholesterol concentration. There was no significant association between alleles of the apo AII MspI RFLP and genetic variation determining apo AII or HDL concentration. The data demonstrate that genetic variation in the apo AI-CIII-AIV gene cluster is involved in determining the serum concentration of apo AI in this sample of clinically well individuals. PMID- 2894760 TI - Cytogenetic and molecular analysis of sex-chromosome monosomy. AB - X chromosome- and Y chromosome-specific DNA probes were used to study different aspects of the genesis of sex-chromosome monosomy. Using X-linked RFLPs, we studied the parental origin of the single X chromosome in 35 spontaneously aborted and five live-born 45,X conceptions. We determined the origin in 35 cases; 28 had a maternal X (Xm) and seven had a paternal X (Xp). There was a correlation between parental origin and parental age, with the Xp category having a significantly reduced mean maternal age by comparison with the Xm group. Studies aimed at detecting mosaicism demonstrated the presence of a Y chromosome or a second X chromosome in three of 33 spontaneous abortions, a level of mosaicism much lower than that reported for live-born Turner syndrome individuals. PMID- 2894759 TI - Pairwise linkage analysis of 11 loci on human chromosome 4. AB - New RFLPs are described for INP10 and interleukin 2. The 55 pairwise genetic linkage relationships for these two loci and nine additional loci on the long arm of chromosome 4 (4q) are reported. Fifteen new linkages are established, and new data are added to the four previously reported linkages on 4q. Tight linkage of interleukin 2 (T-cell growth factor), epidermal growth factor, and alcohol dehydrogenase is described. Significant differences were observed between male and female recombination rates. The female rate was estimated to be 1.27 times the male rate. On the basis of these pairwise results, the order for the 11 loci is D4S35-GC-(ALB/AFP)-MT2P1-D4S1-INP10-ADH3-( EGF/IL2)-(FBB/FBA/FBG)-MNS. This preliminary order can serve as a starting point for more detailed multipoint analysis. PMID- 2894763 TI - Mechanisms of nonsteroidal anti-inflammatory drug-induced gastric damage. Actions of therapeutic agents. AB - All nonsteroidal anti-inflammatory drugs (NSAIDs) used in the treatment of rheumatic diseases may cause gastric mucosal damage. Although the best-studied agent is aspirin, the mechanisms by which it damages the gastric mucosa are not fully understood. However, it is thought that the drug impairs mucosal defenses by penetrating the protective mucous and bicarbonate layers and damaging the epithelial lining cells. In turn, gastric acid is permitted to pour through the breached defenses. This "back-diffusion" of acid further injures cells and destroys capillaries and venules. This local damaging effect is pH dependent and is contributed to by the acid secretion of the stomach. Other mechanisms by which aspirin may induce or contribute to mucosal injury include inhibition of mucosal prostaglandin synthesis, reduction and alteration of mucus secretion, reduction of bicarbonate secretion, interference with cell turnover, as well as systemic effects such as platelet dysfunction. The mechanism by which nonaspirin NSAIDs cause gastrointestinal damage is uncertain. All are known to inhibit prostaglandin synthesis, which could contribute to their toxicity since prostaglandins found in the stomach both inhibit acid secretion and have mucosal defensive effects. Partial protections against aspirin-induced or other NSAID induced gastric mucosal damage has been demonstrated, at least in some studies, by sucralfate, prostaglandins, omeprazole and histamine (H2)-receptor antagonists. Sucralfate appears to act primarily on local defensive mechanisms; its antisecretory effects are minimal. Prostaglandins exert a protective effect at both antisecretory and nonantisecretory (cytoprotective) doses, indicating that either or both mechanisms may be involved. The most recently studied agent, omeprazole, is the most potent of all acid inhibitors; it may also be cytoprotective, possibly as a result of its effects on sulfhydryl groups. Prostaglandins and omeprazole are not available in the United States and their potential side effects may limit their use in patients with chronic rheumatic diseases. Protection by H2-receptor antagonists is mostly related to reduction of acid secretion, though a cytoprotective effect may occur. PMID- 2894762 TI - Globin genes are useful markers to identify genetic similarities between Fijians and Pacific Islanders from Polynesia and Melanesia. AB - DNA mapping studies in Fijians have enabled the identification of rearrangements and RFLPs involving the alpha-, zeta-, and gamma-globin genes. Comparisons of these data with corresponding gene markers in Polynesians and Melanesians of Papua New Guinea show considerable overlap between the three population groups. The utility of globin genes as population markers is further confirmed. PMID- 2894761 TI - The gene for cystathionine beta-synthase (CBS) maps to the subtelomeric region on human chromosome 21q and to proximal mouse chromosome 17. AB - The human gene for cystathionine beta-synthase (CBS), the enzyme deficient in classical homocystinuria, has been assigned to the subtelomeric region of band 21q22.3 by in situ hybridization of a rat cDNA probe to structurally rearranged chromosomes 21. The homologous locus in the mouse (Cbs) was mapped to the proximal half of mouse chromosome 17 by Southern analysis of Chinese hamster X mouse somatic cell hybrid DNA. Thus, CBS/Cbs and the gene for alpha A-crystalline (CRYA1/Crya-1 or Acry-1) form a conserved linkage group on human (HSA) chromosome region 21q22.3 and mouse (MMU) chromosome 17 region A-C. Features of Down syndrome (DS) caused by three copies of these genes should not be present in mice trisomic for MMU 16 that have been proposed as animal models for DS. Mice partially trisomic for MMU 16 or MMU 17 should allow gene-specific dissection of the trisomy 21 phenotype. PMID- 2894765 TI - Health hazards of nitrite inhalants. PMID- 2894767 TI - Beta-blocker therapy and clinical depression. PMID- 2894766 TI - Sulfasalazine-induced lupus erythematosus. AB - Pneumonitis, bilateral pleural effusions, echocardiographic evidence of cardiac tamponade, and positive autoantibodies developed in a 43-year-old man, who was receiving long-term sulfasalazine therapy for chronic ulcerative colitis. After cessation of the sulfasalazine and completion of a six-week course of corticosteroids, these problems resolved over a period of four to six months. It is suggested that the patient had sulfasalazine-induced lupus, which manifested with serositis and pulmonary parenchymal involvement in the absence of joint symptoms. Physicians who use sulfasalazine to treat patients with inflammatory bowel disease should be aware of the signs of sulfasalazine-induced lupus syndrome. PMID- 2894764 TI - Long-term effects of almitrine bismesylate on oxygenation during wakefulness and sleep in chronic obstructive pulmonary disease. AB - Hypoxemia in patients with chronic obstructive pulmonary disease (COPD) becomes more pronounced during sleep and can result in a number of serious consequences. Almitrine bismesylate is a peripheral chemoreceptor agonist that improves arterial oxygen tension (PaO2) in patients with COPD during wakefulness. Studies conducted for up to six months suggested the agonist may be useful in the management of nocturnal hypoxemia. In this double-blind, parallel, placebo controlled study, patients with COPD received 50 mg of almitrine bismesylate (n = 9) or placebo (n = 11) twice a day for one year. Almitrine bismesylate increased PaO2 by 8.1 +/- 2.1 mm Hg (mean +/- SEM), decreased arterial carbon dioxide tension by 3.0 +/- 0.7 mm Hg (mean +/- SEM), and increased minute ventilation by 3.1 +/- 0.5 liters/minute (mean +/- SEM) during wakefulness. All of these changes were statistically significant. Five patients in the almitrine bismesylate group and eight patients in the placebo group completed sleep studies prior to and after 56, 180, and 360 days of almitrine bismesylate or placebo administration. Relative to placebo, almitrine bismesylate significantly increased oxygen saturation during sleep without any significant changes in the quantity or quality of sleep. PMID- 2894768 TI - Alcohol withdrawal syndrome. PMID- 2894769 TI - Prenatal diagnosis and carrier detection of Duchenne muscular dystrophy by restriction fragment length polymorphism analysis with pERT 87 deoxyribonucleic acid probes. AB - New methods of prenatal diagnosis based on recombinant deoxyribonucleic acid techniques are assuming increased importance in obstetrics practice. Carrier detection and prenatal diagnosis of Duchenne muscular dystrophy were performed with the use of three intragenic probes and four restriction enzymes to test six polymorphic sites. Twenty-seven families at risk for Duchenne muscular dystrophy were studied. Eleven at-risk pregnancies were studied; two affected males and four carrier females were predicted. Some families with a single affected individual were shown to have had a spontaneous mutation and were therefore at a much lower risk in future pregnancies. PMID- 2894770 TI - Development of the biphasic response to glucose in fetal and neonatal rat pancreas. AB - A study on the development of biphasic insulin release and sensitivity to inhibitors has been performed using perifused rat pancreas at 19.5 days of gestation (3 days before birth) and at 3 days after birth. In the fetal pancreas, 16.7 mM glucose caused a marked stimulation of insulin release that did not, however, manifest a biphasic response and was not inhibited by verapamil, a Ca2+ channel blocker. This suggested that the immature response was due to either a lack of voltage-dependent Ca2+ channels or their failure to open in response to glucose. Depolarizing concentrations of KCl stimulated insulin release, which was inhibited by verapamil, demonstrating that functional Ca2+ channels were present. In the presence of 16.7 mM glucose, quinine, which blocks glucose-sensitive k+ channels, potentiated the response of the fetal pancreas that now became sensitive to verapamil, demonstrating that functional K+ channels were also present in the fetal pancreatic beta-cell. The immaturity of the response is not due specifically to a defect in glucose metabolism; rather the metabolism of nutrient secretagogues fails to couple with the K+ channel in the fetal islet and thus fails to depolarize the beta-cell membrane. Three days after birth the pattern of response to high glucose is biphasic. Insulin release in fetal pancreas was inhibited by epinephrine and somatostatin. PMID- 2894771 TI - Hepatic extraction of somatostatin in conscious dogs. AB - Fractional hepatic extraction of endogenous somatostatin immunoreactivity was examined in conscious dogs with Doppler flow probes on the portal vein and hepatic artery and catheters in the portal and hepatic veins and carotid artery before and after induction of hypoglycemia by infusion of insulin. Insulin infusion (1 and 2 mU.kg-1.min-1) decreased arterial plasma glucose from 76 +/- 4 mg/dl to a nadir of 41 +/- 2 mg/dl. Basal portal vein somatostatin was 117 +/- 11 pg/ml, which was significantly greater than the 97 +/- 12 pg/ml in the hepatic vein (P less than 0.05) and 79 +/- 8 pg/ml in the carotid artery (P less than 0.05). Hypoglycemia significantly augmented portal vein somatostatin to 206 +/- 32 pg/ml with parallel increases in the hepatic vein and carotid artery. The mean basal fractional hepatic extraction of total somatostatin immunoreactivity was 9 +/- 6% and was unchanged during hypoglycemia (14 +/- 4%). Column chromatography of the portal vein somatostatin immunoreactivity in the basal period yielded three peaks with most of the material eluting with somatostatin-14 and the void volume. Very little somatostatin-28 was detected. There was very little hepatic extraction of the void volume material while approximately 50% of somatostatin-14 was removed by that organ. After insulin-induced hypoglycemia, there was the greatest percent increase in somatostatin-28 and a doubling of somatostatin-14 and the void volume material. Most of the somatostatins-14 and -28 were removed by the liver, while extraction of the void volume material was negligible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894772 TI - Effect of somatostatin on basal and stimulated gastric secretion in the cod, Gadus morhua. AB - In vivo secretion of gastric acid and pepsin has been studied in pylorus-ligated cod. Basal acid output amounted to 100-150 mumol H+.kg-1.h-1 and pepsin secretion to 1 mg.kg-1.h-1. In response to bombesin nonapeptide (2.4 nmol.kg-1.h-1) and histamine (81 nmol.kg-1.h-1), acid secretion increased to approximately 200 and 600% of the basal level, respectively. Pepsin output was marginally affected by histamine but increased to approximately 3 and 15 times the basal level during treatment with bombesin and eledoisin (3.27 nmol.kg-1.h-1). Somatostatin (SS-14, 15 nmol.kg-1.h-1) inhibited basal acid secretion by 85%. It also inhibited the acid secretion during stimulation with bombesin (68%) and histamine (57%), but although the former effect could be explained by removal of the basal component, the latter could not. Basal pepsin secretion was not affected by SS-14. A slight inhibition (28%) of the peak pepsin response to eledoisin was demonstrated, and bombesin failed to stimulate pepsin secretion during treatment with SS-14. These results indicate that endogenous somatostatin, if present in the cod stomach, could play a role in the regulation of gastric secretion. PMID- 2894773 TI - Somatostatin modulates cholinergic neurotransmission in canine antral muscle. AB - Somatostatin has been shown to inhibit antral motility in vivo. To examine the effect of somatostatin on cholinergic neurotransmission in the canine antrum, we studied the mechanical response of and the release of [3H]acetylcholine from canine longitudinal antral muscle in response to substance P, gastrin 17, and electrical stimulation. In unstimulated tissues, somatostatin had a positive inotropic effect on spontaneous phasic contractions. In tissues stimulated with substance P and gastrin 17, but not with electrical stimulation, somatostatin inhibited the phasic inotropic response dose dependently. This inhibitory effect was abolished by indomethacin. Somatostatin stimulated the release of prostaglandin E2 radioimmunoreactivity, and prostaglandin E2 inhibited the release of [3H]acetylcholine induced by substance P and electrical stimulation. Somatostatin increased the release of [3H]acetylcholine from unstimulated tissues by a tetrodotoxin-sensitive mechanism but inhibited the release induced by substance P and electrical stimulation. These results suggest that somatostatin has a dual modulatory effect on cholinergic neurotransmission in canine longitudinal antral muscle. This effect is excitatory in unstimulated tissues and inhibitory in stimulated tissues. The inhibitory effect is partially mediated by prostaglandins. PMID- 2894774 TI - Sites of action of mu-, kappa- and sigma-opiate receptor agonists at the feline ileocecal sphincter. AB - The sites of action of several opiate agonists at the feline ileocecal sphincter (ICS) were studied. Dose-response curves for the relatively specific ligands for the mu-, kappa-, and sigma-receptors were determined using morphine (mu receptors), dynorphin-(1-13) (kappa-receptors), and N-allylnormetazocine (sigma receptors). Each agonist results in a contractile ICS response. The ICS responded stereospecifically to the levo-isomer of N-allylnormetazocine. Atropine (30 micrograms/kg) or naloxone (100 micrograms/kg) antagonized the ICS response to morphine and to (-)-N-allylnormetazocine. Higher doses of naloxone were required to inhibit the ICS response to dynorphin. Neither atropine nor tetrodotoxin inhibited the ICS response to dynorphin. The ICS response to dynorphin was enhanced after tetrodotoxin. Morphine tachyphylaxis inhibited the ICS response to (-)-N-allylnormetazocine and vice versa. The ICS response to morphine was unaffected by vagotomy but inhibited by trimethaphan camsylate. This study suggests that dynorphin (kappa-receptor) acts at a smooth muscle receptor to mediate contraction and a neural receptor to mediate relaxation, while (-)-N allylnormetazocine acts at the ICS via a mu-receptor. mu-Receptor activation causes ICS contraction via a cholinergic pathway. PMID- 2894776 TI - Phorbol esters, protein kinase C, and thyroxine 5'-deiodinase in brown adipocytes. AB - Protein kinase C activity has been identified in the rat brown adipocyte. About 60% of this activity is found in the cytosolic fraction under basal conditions, and 12-O-tetradecanoylphorbol 13-acetate (TPA) causes a rapid shift from the cytosol to the particulate fraction. Norepinephrine and phenylephrine cause a similar redistribution that can be blocked by prazosin but not by alprenolol. alpha 1-Adrenergic agonists cause three- to fivefold stimulation of type 2 iodothyronine 5'-deiodinase activity in brown adipocytes. TPA has no effect on basal deiodinase activity and reduces the response of the enzyme to alpha 1 adrenergic agonists. These results suggest that the translocation of protein kinase C from cytosol to particulate fraction is not sufficient to increase deiodinase activity but can modulate the alpha 1-adrenergic agonist-mediated responses in these cells. PMID- 2894775 TI - Beta-adrenergic actions on membrane electrical properties of dissociated smooth muscle cells. AB - Studies were carried out to determine the effects of the beta-adrenergic agent, isoproterenol (ISO), on membrane electrical properties in single smooth muscle cells enzymatically dispersed from toad stomach. In cells bathed in buffer of physiological composition, the average resting potential was -56.4 +/- 1.4 mV (mean +/- SE, n = 35). The dominant effect of exposure to ISO was hyperpolarization. The hyperpolarization was apparent in all cells studied and averaged 11.6 +/- 1.2 mV (n = 27). In the majority of the cells, hyperpolarization was accompanied by a decreased input resistance (Rin). Often the change in resistance appeared to lag behind the change in membrane potential. The lack of coincident changes in membrane potential and resistance may reflect a superposition of the outward rectification properties of the membrane on beta adrenergic-induced increases in ionic conductance. In about half of the cells, an initial small depolarization (3.1 +/- 0.3 mV, n = 14) was accompanied by a small but distinct increase in Rin (12 +/- 2.5%). When membrane potential was made more negative than the estimated equilibrium potential for K+ (EK) by injection of current, ISO also produced biphasic effects, an initial hyperpolarization which reversed to a sustained depolarization to a value (-90 mV) near the estimated EK. The hyperpolarization by ISO could be diminished in a time-dependent manner by previous exposure to ouabain. The inhibition by ouabain, however, appeared to be a fortuitous result of glycoside-induced positive shifts in EK. These observations indicate that the dominant electrophysiological effect of beta adrenergic stimuli is to hyperpolarize the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894777 TI - Effects of somatostatin on splanchnic hemodynamics and plasma glucagon in portal hypertensive rats. AB - The effects of somatostatin infusion on splanchnic and systemic hemodynamics and plasma glucagon levels were investigated in rats with portal hypertension. Forty four male Sprague-Dawley rats were studied. Portal hypertension was induced in 26 rats by partial portal vein ligation (PVL). These rats were divided in two experimental groups to receive blindly 1) somatostatin (PVL-SMT, n = 13) at a dose of 25 micrograms/kg body wt during 30 min preceded by a bolus injection of 15 micrograms/kg body wt or 2) placebo (saline) (PVL-P, n = 13) infused at the same rate as in the previous group. The remaining 18 rats were used as normal controls and received somatostatin (n = 9) or saline infusion (n = 9). Regional blood flows and cardiac output were measured using radioactive microspheres. Arterial and portal pressures were also measured. In portal hypertensive rats somatostatin infusion produced significant reductions in the increased portal venous inflow, reductions in portal pressure, and significantly increased portal venous resistance. Reduction of portal venous inflow was due to splanchnic vasoconstriction, evidenced by increased splanchnic arteriolar resistance. No significant differences were observed in systemic hemodynamic parameters between PVL-SMT and PVL-P rats. Plasma glucagon levels were significantly reduced by somatostatin to levels similar to those observed in sham-operated rats. In sham operated rats, somatostatin also caused significant reduction in portal venous inflow and plasma glucagon concentration, although these changes were of lesser magnitude than in portal hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894778 TI - Cholinergic neurotransmission in human corpus cavernosum. I. Responses of isolated tissue. AB - To investigate the role of cholinergic neurotransmission in erection, human penile corpus cavernosum tissue was studied. Electrical stimulation of strips of corpus cavernosum suspended in an organ chamber induced contractions and relaxations that were blocked by tetrodotoxin. The contractions also were blocked by bretylium and prazosin. Norepinephrine and phenylephrine contracted the isolated strips and this response was prevented by prazosin. Electrical stimulation-induced relaxations were enhanced by bretylium and physostigmine and partially blocked by atropine. The effect of atropine, but not that of physostigmine, was prevented by bretylium. Corporal strips contracted with norepinephrine relaxed to acetylcholine; this effect was blocked by atropine and enhanced by physostigmine. Strips lacking endothelium contracted normally with norepinephrine, but the relaxation caused by acetylcholine was virtually abolished. Thus endothelium lining the lacunar spaces within human corpus cavernosum is required for the relaxation caused by exogenous acetylcholine. There may be three neurotransmitter effector systems that control corpus cavernosum smooth muscle tone: adrenergic (excitatory), cholinergic (inhibitory), and nonadrenergic noncholinergic (inhibitory). Cholinergic nerves do not dilate or constrict directly the smooth muscle but may modulate other neuroeffector systems and/or the endothelium. PMID- 2894779 TI - Adrenergic modulation of pancreatic glucagon and insulin secretion in sheep. AB - The effect of intravenous infusion of epinephrine, either alone or together with various doses of phentolamine or propranolol, on the secretion of both glucagon and insulin was determined in six sheep. Intravenous infusion of epinephrine alone caused increases in plasma glucagon and glucose concentrations and produced a slight but significant decrease in plasma insulin concentration. The concomitant infusion of propranolol and epinephrine augmented glucagon release and inhibited insulin secretion. Combined propranolol plus epinephrine infusion also caused a marked hyperglycemia. The concomitant infusion of phentolamine and epinephrine produced slight inhibition of glucagon secretion and markedly promoted insulin secretion. Epinephrine-induced hyperglycemia was eliminated by phentolamine infusion. The effects of isoproterenol infusion on plasma glucagon, insulin, and glucose concentrations were similar to that caused by the concomitant infusion of phentolamine and epinephrine. The effects of isoproterenol were abolished by the infusion of propranolol. It is concluded that an alpha-receptor mechanism is the most important component of adrenergic modulation of pancreatic glucagon secretion, whereas beta-receptor activation stimulates and alpha-receptor activation inhibits insulin secretion in sheep. PMID- 2894780 TI - Differential memory function with dopaminergic versus anticholinergic treatment of drug-induced extrapyramidal symptoms. AB - Nine chronic schizophrenic patients being treated with high-potency antipsychotic medication and antiparkinsonian agents were enrolled in a double-blind, crossover trial comparing amantadine and trihexyphenidyl. Memory function was assessed with the Rey Auditory-Verbal Learning Test during each 6-week drug trial. The subjects performed significantly better while receiving amantadine. Examinations of computed tomographic studies of seven subjects revealed a significant inverse correlation between ventricle size and memory while they were taking trihexyphenidyl but not amantadine. This suggests that patients with underlying brain pathology may be particularly vulnerable to the memory-disrupting effects of anticholinergic agents. PMID- 2894781 TI - Meige's syndrome associated with neuroleptic treatment. AB - Meige's syndrome is characterized by blepharospasm and oromandibular dystonia. Three cases are presented; two were associated with long-term neuroleptic administration. This drug-induced syndrome may be a variant of tardive dystonia, and prompt discontinuation of neuroleptic treatment may be therapeutic. PMID- 2894782 TI - A prospective survey of neuroleptic malignant syndrome in a short-term psychiatric hospital. AB - Of 1,470 patients treated with neuroleptics during 1 year at a private psychiatric hospital, only one patient developed neuroleptic malignant syndrome- an annual frequency of 0.07%. Use of low doses of neuroleptics may account for this frequency, which is below recent estimates. PMID- 2894783 TI - Alcohol-induced enhancement of intestinal gamma-glutamyl transpeptidase activity in rats and humans: a possible role in increased serum gamma-glutamyl transpeptidase activity in alcoholics. AB - It is a well-known phenomenon that serum gamma-glutamyltranspeptidase (gamma-GTP, EC 2.3.2.2.) activity is increased after chronic consumption of ethanol, and gamma-GTP has been, therefore, widely used as a sensitive marker for detection of alcoholism and its related liver disease. However, the precise mechanisms whereby the chronic ethanol consumption leads to an increase in serum gamma-GTP activity are not fully understood. In the present study, we investigated the relationship between the intestinal and serum gamma-GTP activities after chronic ethanol consumption both in rats and humans. Chronic ethanol feeding to rats resulted in a significant increase in serum gamma-GTP activity associated with a significant increment of the intestinal gamma-GTP activity. The histochemical staining of gamma-GTP in the mucosa of the small intestine of these animals demonstrated enhanced gamma-GTP activity at the microvilli of the brush border membrane, lamina propria of the mucosa, and endoplasmic reticulum of the intestinal epithelial cell. The augmented activity in the lamina propria was mainly localized at the submucosal lymphatics. Histology of the small intestine of human alcoholics was, more or less, similar to those observed in alcoholic rats. We further investigated the gamma-GTP activity in the mesenteric lymph using the animal model of lymphorrhea, and found that the gamma-GTP activity was increased by 83% when expressed per unit of lymph in the ethanol-fed rat, accompanied by a marked decrease of serum gamma-GTP activity, suggesting a close relationship between the serum and the intestinal gamma-GTP via the lymphatic channel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894784 TI - Ontogeny of immunoreactive calcitonin gene-related peptide in thyroid C cells from dogs, rabbits, and guinea pigs. AB - Ontogeny of immunoreactive calcitonin gene-related peptide (CGRP) in thyroid C cells of dogs, rabbits, and guinea pigs from early fetuses to adults was investigated by an immunoperoxidase method, in comparison with the development of immunoreactive calcitonin and somatostatin. The presence of immunoreactive CGRP in mature C cells was different from species to species. Dog and rabbit C cells revealed intense immunoreactivity for CGRP, whereas guinea pig C cells revealed very weak immunoreactivity or none. In dog fetuses, the appearance of immunoreactive CGRP was early. At around 35 days of gestation, when the follicular cells were not yet organized into follicles, immunoreactivities for three peptides--calcitonin, somatostatin, and CGRP--began to appear in C cells. While the highest population of somatostatin-positive cells was attained when the primordial follicles were vigorously formed throughout whole thyroid parenchyma and their frequency progressively declined thereafter, CGRP-positive cells as well as calcitonin-positive cells gradually increased in number and intensity with gestational age. The developmental pattern of immunoreactive CGRP coincided with that of immunoreactive calcitonin in dog C cells. In rabbit fetuses, at 25 days of gestation, when thyroid follicles stored large amounts of colloid and C cells already exhibited intense immunoreactivity for calcitonin, CGRP immunoreactivity as well as somatostatin immunoreactivity began to appear. Subsequently, immunoreactivities for the three peptides gradually increased with age, although calcitonin immunoreactivity was outstandingly intense among them. In guinea pig C cells, intense immunoreactivity for CGRP was not observed in any stages of development. These results indicate that there are developmental profiles of CGRP characteristic for each animal, and the ratio of CGRP and calcitonin produced from calcitonin genes in C cells seems to be fixed for life. PMID- 2894785 TI - Molecular genetic analysis of the major histocompatibility complex in an ELA typed horse family. AB - Restriction fragment length polymorphism was studied in an ELA typed horse family which included a stallion, a mare with two full-sibs, another mare with three full-sibs and, in addition, three paternal half-sibs. DNA samples from all individuals were investigated by Southern blot analysis using three restriction enzymes (EcoRI, HindIII or TaqI) and human cDNA class I, class II (DR beta) and class III (C4) probes. In addition, a genomic class II DQ alpha probe was used. Fragments hybridized with the various probes revealed the existence of DNA sequences homologous to HLA class I, DR beta, DQ alpha and C4 genes in the horse. Polymorphic fragments were found when DNA was hybridized with class I and class II probes irrespective of the enzyme used; but hybridization with the C4 probe did not reveal variability. All polymorphic fragments segregated according to the ELA serological specificities, thus indicating a close linkage between the different revealed subregions. Banding patterns suggest that the horse possesses about 20-30 class I genes, probably more than one DR beta and DQ alpha genes and possibly only one C4 gene. The high degree of polymorphism observed suggests that molecular DNA typing may represent a potentially powerful aid to decision in parentage control determination. PMID- 2894786 TI - Immunologically mediated food allergy: the importance of food challenge procedures. AB - The past several years have witnessed a growing public awareness and concern about adverse reactions to foods. Although the scientific community's interest in this topic has grown also, much needs to be learned about the prevalence, etiology, and symptoms related to these disorders. Reasons why double-blind placebo-controlled food challenges are mandatory for the diagnosis of food allergy in the research setting are discussed. A practical office approach for evaluating complaints of potential adverse reactions to foods is presented. PMID- 2894788 TI - [Repeated convulsions after abrupt benzodiazepine withdrawal]. AB - Benzodiazepines are widely used and well-known for their safety; serious complications may, nevertheless, occur in the particular case of an abrupt withdrawal, which is quite common after general anaesthesia. The case reported emphasizes the seriousness of the syndrome : after vascular surgery the patient presented with repeated epileptic seizures and a short lasting cardiac arrest. The patient used to absorb large quantities of benzodiazepines, without medical prescription. The convulsions stopped after the benzodiazepine had been taken again. The exact mechanism of the withdrawal syndrome remains hypothetical. There are numerous risk factors which increase the probability and seriousness of the withdrawal symptoms. The prevention of withdrawal accidents depends on the physician, and especially the anesthetist, knowing the patient's drug intake. This shows yet again the importance of the preanaesthetic visit. PMID- 2894787 TI - [Spontaneous development of paralysis induced by equipotent doses of vecuronium, atracurium, fazadinium, pancuronium, gallamine and d-tubocurarine]. AB - Thirty-six patients undergoing elective surgery were studied after obtaining their informed consent. They were randomly assigned to six series of six patients each. One hour before anaesthesia, all patients received 0.2 mg.kg-1 diazepam orally. After induction of anaesthesia with 1-1.5 mg.kg-1 methohexitone and 5 micrograms.kg-1 fentanyl, the patients were paralysed and ventilation was controlled manually (semi-open circuit; 50% N2O/50% O2). Each patient received a single dose of either 70 micrograms.kg-1 fazadinium, 70 micrograms.kg-1 pancuronium, 2,500 micrograms.kg-1 gallamine or 450 micrograms.kg-1 d tubocurarine. Neuromuscular function was monitored by measuring the isometric contraction of the adductor pollicis muscle in response to supramaximal stimulations of the ulnar nerve at the wrist (square wave pulse of 0.2 ms duration at supramaximal intensity delivery at 0.1 Hz). Three parameters were measured: the time between the injection of the relaxant drug and recovery of the twitch height at 50% of its baseline (RT0-50); the time between the injection of the relaxant drug and recovery of the twitch height at 90% of its baseline (RT0 90); the time between the injection of the relaxant drug and recovery of the twitch height from 25 to 75% of its baseline (RT25-75). The values of the observed parameters were expressed in minutes (means +/- SEM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894789 TI - [Comparison of the action kinetics of alcuronium and vecuronium by electromyographic monitoring]. AB - Twenty-eight ASA I or ASA II adults undergoing microsurgery were anaesthetized according to a standard protocol using droperidol, phenoperidine and thiopentone followed by enflurane. The patients were randomly assigned to two homogeneous groups: the first group (n = 14) received 0.2 mg.kg-1 alcuronium, whereas the second group (n = 14) received 0.08 mg.kg-1 vecuronium. There was no reinjection of either drug and curarization tapered off spontaneously. Neuromuscular monitoring was begun once anaesthesia was stable and after intentional isovolaemic haemodilution. The type of stimulus used was the train-of-four, delivered by a Relaxograph monitor to the ulnar nerve. Muscle response was measured at the hypothenar eminence. The kinetic study considered the time interval required between the injection of the muscle relaxant and the appearance of the minimal value of the twitch (first response of the train-of-four = T1min). The times to recovery of the twitch height to 25, 75 and 100% of the reference value (T1/T0) and of the fourth response of the train-of-four to 25 and 75% of the ratio (T4/T1) were also recorded. Finally, the recovery indexes represented by the times required for T1/T0 and T4/T1 to rise from 25% to 75% respectively were studied. The maximal twitch height inhibition was significantly greater (p less than 0.001) in the vecuronium group (T1min = 0.36 +/- 1.33%) than in the alcuronium group (T1min = 4.36 +/- 5.08%); it occurred significantly more quickly (p less than 0.001) with vecuronium (139 +/- 48 s) than with alcuronium (316 +/- 133 s).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894790 TI - Experimental induction of abdominal tympany, abomasitis, and abomasal ulceration by intraruminal inoculation of Clostridium perfringens type A in neonatal calves. AB - The etiologic role of Clostridum perfringens type A in the acute abdominal syndrome characterized by abomasal and rumen tympany, abomasitis, and abomasal ulceration was investigated in neonatal calves. Eight calves, 4 to 12 days old, were inoculated intraruminally with toxigenic C perfringens type A. Before and after C perfringens inoculation, blood samples were collected from all calves for blood gas and serum biochemical analysis and for determination of serum copper concentration; ruminal fluid was obtained for isolation of C perfringens. Calves were monitored daily for clinical signs of the syndrome and, depending on the severity of clinical signs, they were either euthanatized or redosed within 4 to 7 days. After necropsy, specimens obtained from the abomasum and rumen for macroscopic and microscopic examination and for anaerobic bacteriologic culture were processed in routine manner. Intraruminal inoculation of C perfringens type A into healthy calves induced anorexia, depression, bloat, diarrhea, and in some calves, death. Serum copper concentration was within normal range. Necropsy revealed variable degrees of abomasitis, petechial and ecchymotic hemorrhages, and ulcers (ranging from pinpoint to nearly perforate) in the abomasum. Seven of those calves also had multiple trichobezoars in the rumen. These necropsy findings were not seen in calves (controls) given distilled H2O only. In affected calves, acute abdominal syndrome was unrelated to copper deficiency, and C perfringens type A given intraruminally was able to induce clinical signs similar to those of the naturally acquired disease. PMID- 2894791 TI - Continuous narcotic infusion with patient-controlled analgesia for chronic cancer pain in outpatients. AB - STUDY OBJECTIVE: To determine the feasibility and safety of outpatient continuous narcotic infusions with additional bolus capabilities (patient-controlled analgesia) in patients with cancer pain. DESIGN: A single arm (non-randomized) series. SETTING: Outpatient with contact by telephone and through outpatient clinic. PATIENTS: Consecutive series of 18 patients with poorly controlled cancer pain or significant side effects from regular administration of various narcotics. INTERVENTIONS: Patients taught and supervised to use portable pump capable of delivering a continuous narcotic infusion with bolus capabilities. MEASUREMENTS AND MAIN RESULTS: All patients had improvement in pain control as judged by the use of a linear analogue scale. Side effects and safety profile were highly acceptable. Narcotics used and maximum doses were meperidine, 50 mg/h; morphine, 80 mg/hr; and hydromorphone, 60 mg/hr. Infusion duration ranged from 7 to 225 days (mean, 54 days). CONCLUSIONS: Continuous narcotic infusions using a programmable portable pump with bolus capabilities is a safe and reliable method of delivering narcotics to outpatients. PMID- 2894792 TI - [Manic switch induced by clorazepate (5 cases)]. PMID- 2894793 TI - Redox drug delivery systems for targeting drugs to the brain. PMID- 2894794 TI - Multidrug resistance and P-glycoprotein expression. PMID- 2894795 TI - Multiple factors controlling ACTH secretion at the anterior pituitary level. PMID- 2894796 TI - Role of altered heme synthesis in chemical injury to the nervous system. PMID- 2894797 TI - Expression of the myc protooncogene in canine rhabdomyosarcoma. AB - The expression of the protooncogene c-myc in a canine rhabdomyosarcoma was examined. It was found that this highly malignant tumour contained vast quantities of RNA that hybridized with a cDNA probe for c-myc. Restriction fragment length analysis after endonuclease digestion of tumour DNA did not reveal any rearrangements in this gene locus. The potential role of this oncogene in the development of canine rhabdomyosarcoma is discussed. PMID- 2894799 TI - Retroviruses in the nervous system. Proceedings of a symposium sponsored by the National Institutes of Health, Bethesda, Maryland, May 4-6, 1987. PMID- 2894798 TI - Induction of ornithine decarboxylase activity in rat lung by neurotransmitters and peptide hormones. AB - Ornithine decarboxylase activity of rat lung was induced by s.c. injection of acetylcholine, norepinephrine, epinephrine, dopamine, serotonin, vasopressin, angiotensin II, and adrenocorticotropic hormone, but not by gonadotropin, aldosterone, corticosterone or hydrocortisone. The possible significance of hormonal factors in lung carcinogenesis is discussed, based on the reported promoting activity of vasopressin in cultured cells. PMID- 2894800 TI - The neuroepidemiology of tropical spastic paraparesis. AB - Recent neuroepidemiological studies of endemic tropical spastic paraparesis (TSP) have confirmed the existence of high-prevalence foci in several tropical islands, including Jamaica and Martinique in the Caribbean, Tumaco off the Pacific coast of Colombia, and the Seychelles in the Indian Ocean. There is a net preponderance of TSP in persons of Black African ancestry, although Caucasian, Hindu, Amerindian, and Orientals have been affected. The epidemiological, clinical, laboratory, and neuropathological features of TSP are reviewed here, as well as the evidence in favor of its retroviral origin. PMID- 2894801 TI - The role of HTLV-I in tropical spastic paraparesis in Jamaica. AB - We report clinical and laboratory investigations of 47 native-born Jamaican patients with endemic tropical spastic paraparesis and of 1 patient with tropical ataxic neuropathy. Mean age at onset was 40 years, with a female-male preponderance (2.7:1). Neurological features of endemic tropical spastic paraparesis are predominantly those of a spastic paraparesis with variable degrees of proprioceptive and/or superficial sensory impairment. Using enzyme linked immunoabsorbent assay (ELISA), IgG antibodies to human T-lymphotropic virus type I (HTLV-I) were present in 82% of sera and 77% of cerebrospinal fluids. On Western blot analysis, IgG antibodies detected the p19 and p24 gag encoded core proteins in both serum and cerebrospinal fluid. Titers were tenfold higher by ELISA in serum than in cerebrospinal fluid, and some oligoclonal bands present in fluid were not seen in serum. Serum-cerebrospinal fluid albumin ratios were normal, and IgG indexes indicated intrathecal IgG synthesis. Histopathological changes showed a chronic inflammatory reaction with mononuclear cell infiltration, perivascular cuffing, and demyelination that was predominant in the lateral columns. In 1 patient, a retrovirus morphologically similar to HTLV-I on electron microscopy was isolated from spinal fluid. Our investigations show that endemic tropical spastic paraparesis in Jamaica is a retrovirus associated myelopathy and that HTLV-I or an antigenically similar retrovirus is the causal agent. PMID- 2894802 TI - Tropical spastic paraparesis in Colombia. AB - A high-incidence focus of tropical spastic paraparesis (TSP) occurs on the South Pacific coast of Colombia. Of 55 patients studied, 52 (94.5%) had IgG antibodies to the human T-cell lymphotropic virus type I (HTLV-I) in serum and/or cerebrospinal fluid. Control groups did not show similar high positivity. Our results suggest that HTLV-I or other antigenically related retroviruses may be the cause of TSP in Colombia. Similar clinical, laboratory, and epidemiological findings have been reported in widely remote geographical regions of the world, with very similar clinical pictures of TSP in all high-incidence regions. The demonstration of IgG antibodies in serum and cerebrospinal fluid of patients with TSP in the Caribbean and Seychelles Islands, southern Japan, and the Ivory Coast indicate that the HTLV-I retrovirus could be the cause of this "tropical" myeloneuropathy. PMID- 2894803 TI - Primary central nervous system lymphomas in patients with AIDS. AB - Primary central nervous system non-Hodgkin's lymphomas are observed in approximately 1.9% of all patients with acquired immunodeficiency syndrome (AIDS). The yearly incidence of AIDS-associated tumors has surpassed the yearly incidence from all other causes and could become as frequent as low-grade astrocytomas by 1991. Patients' signs, symptoms, and radiographic studies are not specific for this lesion; brain biopsy usually is necessary to make a definitive diagnosis. Most tumors are high-grade lymphomas and are pathologically similar to the primary central nervous system lymphomas observed before the AIDS epidemic. AIDS-associated tumors respond readily to radiation therapy. However, patient survival remains limited owing to other manifestations of the syndrome. PMID- 2894804 TI - HTLV-I-associated tropical spastic paraparesis in Martinique: a reappraisal. AB - Human T-lymphotropic virus type I (HTLV-I)-associated tropical spastic paraparesis in Martinique has been identified in 54 patients, 49 women and 5 men. This myelopathy represents an endemic problem on this island and the earliest documented case dates from 1952. A blood transfusion history was obtained in 7 of the 54 patients (13%). There was a preponderance of cases from the northern Atlantic coast of Martinique, the most humid region on the island. The prevalence in this region reached 49.5 per 100,000, compared with the global prevalence of 11.9 cases per 100,000 for the island. An immune-mediated mechanism may be important in the pathogenesis of HTLV-I-associated tropical spastic paraparesis. PMID- 2894805 TI - Tropical spastic paraparesis: clinical, immunological, and virological studies in two patients from Martinique. AB - Two patients from Martinique with tropical spastic paraparesis had antibodies to human T-lymphotropic virus type I (HTLV-I) in serum and spinal fluid but no antibodies to other retroviruses tested. They presented with spastic weakness of both lower extremities, hyperreflexia with upgoing toes, sphincteric dysfunction, and normal sensation. By means of agarose isoelectric focusing and selective immunoblotting we demonstrated an increased intrathecal synthesis of IgG antibodies to HTLV-I in the spinal fluid. Unique oligoclonal bands of IgG antibodies to HTLV-I were present in the cerebrospinal fluid. Using a battery of monoclonal antibodies we also found in these patients an increased number of circulating T cells that expressed activation markers. We conclude that the HTLV I retrovirus associated with tropical spastic paraparesis has both lymphocytotropic and neurotropic properties. PMID- 2894806 TI - HLA haplotype-linked high immune responsiveness against HTLV-I in HTLV-I associated myelopathy: comparison with adult T-cell leukemia/lymphoma. AB - HLA haplotypes of 27 patients with human T-lymphotropic virus type I (HTLV-I) associated myelopathy (HAM) and 12 patients with adult T-cell leukemia/lymphoma (ATLL) were examined by analyzing HLA types of the patients and their family members. Either A11Bw54Cw1DR4DQw3, A24Bw54Cw1DR4DQ-, A24B7Cw7DR1DQw1, or A24Bw52Cw-DR2DQw1 and the related haplotypes were found in 70% of cases with HAM. None of these "HAM-associated" haplotypes was found in patients with ATLL. HLA haplotypes made up of HLA components of A26Bw62Cw3DR5DQw3 and one particular haplotype of Aw33B44Cw-DRw6DQw1 were associated with the ATLL haplotypes. These "ATLL-associated" haplotypes were also found in the patients with HAM who had no previous history of blood transfusion. The in vitro cultures of peripheral blood lymphocytes with HTLV-I virion antigens revealed that the response with HAM peripheral blood lymphocytes was remarkably higher than that with ATLL peripheral blood lymphocytes. Based on this HTLV-I-specific immune responsiveness, we can segregate the high responders in HAM (14 of 16 cases) and the low responders in ATLL (6 of 7 cases). The existence of high and low responders was also confirmed by the normal healthy individuals, whose responses were segregated with HAM associated and ATLL-associated haplotypes. These results suggested that two ethnic groups in southern Kyushu may get the two different diseases, HAM and ATLL, because of their different immunogenetic backgrounds. The high immune response to HTLV-I seems to be an important genetic factor in the development of HAM. PMID- 2894807 TI - Spastic paraparesis and HTLV-I infection in Peru. AB - Three of 6 patients with spastic paraparesis in Lima, Peru, were found to have antibodies to human T-lymphotropic virus type I (HTLV-I). Blood and cerebrospinal fluid antibodies were confirmed by Western blot analysis. Multilobulated lymphocytes in blood and cerebrospinal fluid of the index case stained with monoclonal antibodies for T-helper cells and for T10, an activation marker. Blood mononuclear cells from patients with HTLV-I-associated myelopathy showed spontaneous proliferation in culture, evidence of interleukin-2 receptors, and decreased natural killer cell activity. PMID- 2894808 TI - Pathological and immunological observations on tropical spastic paraparesis in patients from Jamaica. AB - The neuropathological examination of the spinal cord of 2 Jamaican patients with classical tropical spastic paraparesis disclosed an intense chronic meningomyelitis with demyelination. In the 1 case in which serum and cerebrospinal fluid were available, antibodies to the human T-lymphotropic virus type 1 were found. PMID- 2894809 TI - Epidemiology of tropical spastic paraparesis in Columbia and associated HTLV-I infection. AB - The clinical syndrome earlier designated as paraparesia espastica del Pacifico is an isolated form of tropical spastic paraparesis (TSP) that was reported in 1981 in the southern Pacific lowlands of Columbia in and near Tumaco. The clinical features are similar to those of TSP reported in Jamaica, Martinique, the Seychelles, and the Ivory Coast of Africa and resemble also those clinical features of the human T-lymphotropic virus type I (HTLV-I)-associated myelopathy described in southern Japan. Since HTLV-I infection is closely associated with TSP, we conducted a case-control study to evaluate the role of HTLV-I-associated risk factors among patients from the endemic focus in Tumaco, Colombia, and the seroprevalence rates of this virus in other geographical areas of the Pacific Colombian lowlands with and without TSP. From our seroprevalence study of antibodies to HTLV-I among TSP index patients, matched controls, household contacts (first- and second-degree relatives), and healthy controls from these areas, we found a strong association between HTLV-I and TSP. Also, there is a high seroprevalence of HTLV-I among sexual partners of patients and to a lesser extent among their offspring and other relatives some of whom had an early mean acquisition of antibodies to HTLV-I. Heterosexual promiscuity and other close interpersonal contact may play an important role in the transmission of TSP in the Pacific lowlands of Colombia. PMID- 2894811 TI - HTLV-I, adult T-cell leukemia, and tropical spastic paraparesis. AB - Human lymphotropic retroviruses have been identified as the etiological agents of adult T-cell leukemia and acquired immunodeficiency syndrome (AIDS). Human T lymphotropic virus type I (HTLV-I) has been linked to the etiology of ATL, and human immunodeficiency virus type I (HIV-1) has been identified as the cause of AIDS. Both retroviruses are T-cell tropic. HTLV-I is a transforming virus, whereas HIV-1 is a cytopathic virus and kills the cells it infects. HTLV-I has recently been identified from some patients with tropical spastic paraparesis, and it appears that HTLV-I infection alone or in the presence of other cofactors may be important in the development of this neurological dysfunction. PMID- 2894810 TI - HTLV-I-associated leukemia: a model for chronic retroviral diseases. AB - Human T-lymphotropic virus type I (HTLV-I) has been associated with adult T-cell leukemia/lymphoma (ATL), a malignancy of mature CD4-positive lymphocytes, and with tropical spastic paraparesis (TSP), a demyelinating neurological syndrome. This article describes the clinical and pathological features of ATL and reviews the epidemiology of this disease and of its putative etiological agent, HTLV-I. From what is known about the molecular biology and epidemiology of HTLV-I, hypotheses on the etiology of TSP are proposed, and strategies for studying the neurological syndrome are suggested. PMID- 2894812 TI - Intrathecal synthesis of IgG antibodies to HTLV-I supports an etiological role for HTLV-I in tropical spastic paraparesis. AB - High titers of antibody to human T-lymphotropic virus type I (HTLV-I) have been reported in the sera and cerebrospinal fluids of patients with tropical spastic paraparesis. By means of agarose isoelectric focusing and selective immunoblotting, we demonstrated oligoclonal bands of immunoglobulin G antibodies to HTLV-I in the serum and cerebrospinal fluid of patients with tropical spastic paraparesis. Such cerebrospinal fluid-specific immunoglobulin bands indicate intrathecal synthesis of specific antibodies to HTLV-I. These findings mimic the antibody response to measles virus in subacute sclerosing panencephalitis and support an etiological role for HTLV-I in the pathogenesis of tropical spastic paraparesis. PMID- 2894813 TI - Seroprevalence of antibodies to HTLV-I in patients with chronic neurological disorders other than tropical spastic paraparesis. AB - Human T-lymphotropic virus type I (HTLV-I), the etiological agent of adult T-cell leukemia/lymphoma, also appears to be the cause of tropical spastic paraparesis, a chronic myelopathy reported in several different regions of the world. The prevalence of antibodies to HTLV-I in patients with chronic neurodegenerative disorders other than tropical spastic paraparesis and in patients with some muscle inflammatory disorders has been investigated. IgG antibodies to HTLV-I were measured in the sera and/or cerebrospinal fluid from 82 Guamanian patients with amyotrophic lateral sclerosis and parkinsonism-dementia, 164 Guamanian normal controls, 10 patients with kuru from the Eastern Highlands of Papua New Guinea, 4 patients with Viliuisk encephalomyelitis from the Iakut region of eastern Siberia, 45 Italian patients with multiple sclerosis, and 56 patients with polymyositis (49 from the United States and 7 from Jamaica). As determined by enzyme-linked immunosorbent assay, Western immunoblot, and gelatin particle agglutination techniques, serological evidence of HTLV-I infection was found in 1 patient with amyotrophic lateral sclerosis and 1 control subject from Guam, and in 1 patient from the United States and all 7 Jamaican patients with polymyositis. Except for the high seropositivity rate among the group of Jamaican patients with polymyositis, our data indicate that HTLV-I is an unlikely causative agent in the spectrum of the neurological diseases examined. The seropositivity of the 7 Jamaican patients with polymyositis requires further study. PMID- 2894814 TI - Immunological findings in neurological diseases associated with antibodies to HTLV-I: activated lymphocytes in tropical spastic paraparesis. AB - A retrovirus involvement in the etiology of certain neurological diseases is currently an area of intense interest. Tropical spastic paraparesis and other chronic progressive myelopathies have been clearly associated with increased serum and cerebrospinal fluid antibody titers to human T-lymphotropic virus type I; however, little is known about the cellular immune response. In the present study, activated T-lymphocytes were found in the peripheral blood of patients with this disorder. There were increased numbers of large CD3-positive cells that also expressed histocompatibility leukocyte Class II (DR) and interleukin 2 receptor molecules. In addition, a significantly elevated spontaneous lymphoproliferative response was demonstrated in all patients. This is consistent with the known in vitro effects of human T-lymphotropic virus type I. In one patient, a defect in the generation of measles virus-specific cytotoxic T cells was identified. These observations indicate abnormalities of the cellular immune response in tropical spastic paraparesis. PMID- 2894815 TI - Clinical Research. PMID- 2894816 TI - Virological and immunological findings. PMID- 2894817 TI - Antimicrobial susceptibilities of Bordetella species isolated in a Multicenter Pertussis Surveillance Project. AB - MICs for 90% (MIC90s) of 75 Bordetella pertussis strains for amoxicillin, erythromycin, rifampin, and sulfamethoxazole-trimethoprim were 1, less than or equal to 0.12, 1, and 4 micrograms/ml, respectively. Susceptibility rates were all greater than or equal to 93%. Only 17% of the strains were susceptible to tetracycline. The MIC90s of ciprofloxacin, enoxacin, norfloxacin, ofloxacin, and roxithromycin were less than or equal to 0.06, 0.5, 0.25, 0.12, and 0.5 micrograms/ml, respectively. For B. parapertussis, the MIC90s were 16-fold higher with amoxicillin and rifampin and 2- to 4-fold higher with the fluoroquinolones and roxithromycin. PMID- 2894818 TI - Two mutations of dihydropteridine reductase deficiency. AB - Two patients with dihydropteridine reductase (DHPR) deficiency, in one case due to the absence of any enzyme protein (DHPR- cross reactive material (CRM)-) and in the other case due to the production of a mutant type devoid of catalytic activity (DHPR- CRM+) were examined. This latter form of malignant phenylketonuria, whose relative frequency seems to be higher in the Italian population, possibly has a worse prognosis. The earlier onset and the greater severity of clinical symptoms are associated with a more pronounced hydroxylation defect, as shown by higher degree of neonatal hyperphenylalaninaemia, unresponsiveness to an oral tetrahydrobiopterin load, lower concentrations of neurotransmitter metabolites, and reduced tyrosine production after an oral phenylalanine load. PMID- 2894819 TI - Transient neonatal hyperthyroidism and maternal thyroid stimulating immunoglobulins. AB - Serum thyroid stimulating hormone binding inhibitor immunoglobulins (TBII) and thyroid stimulating antibody (TSAb) concentrations were measured in three pregnant women with hyperthyroidism and then in their infants. The results suggested that TBII concentrations in infants in the neonatal period or from mothers during the third trimester of pregnancy showed a good correlation with the development of neonatal hyperthyroidism. PMID- 2894822 TI - Effect of famotidine on theophylline clearance in asthma and COPD patients. PMID- 2894821 TI - [Prenatal screening for phenylketonuria in 2 families by trophoblast biopsy]. AB - Prenatal diagnosis of phenylketonuria (PKU) is now available owing to restriction fragment length polymorphism (RFLP) of the phenylalanine hydroxylase gene. Biopsies of chorionic villi were carried ou at 11 weeks gestation in 2 families who had previously a child with the classical form of PKU and who were considered informative after DNA studies. Fetal DNA was extracted and studied with restriction enzymes selected according to the study of each family. Hybridization studies suggested that one fetus was affected by the disease and that the second was normal. Termination of pregnancy was carried out in the first case; however, study of the fetus could not be performed. In the second family, the pregnancy resulted in the delivery of a normal child, as shown by normal phenylalanine level at birth. PMID- 2894820 TI - Enzymic arrangement and allosteric regulation of the aromatic amino acid pathway in Neisseria gonorrhoeae. AB - The pathway construction and allosteric regulation of phenylalanine and tyrosine biosynthesis was examined in Neisseria gonorrhoeae. A single 3-deoxy-D-arabino heptulosonate 7-phosphate (DAHP) synthase enzyme sensitive to feedback inhibition by L-phenylalanine was found. Chorismate mutase and prephenate dehydratase appear to co-exist as catalytic components of a bifunctional enzyme, known to be present in related genera. The latter enzyme activities were both feedback inhibited by L phenylalanine. Prephenate dehydratase was strongly activated by L-tyrosine. NAD+ linked prephenate dehydrogenase and arogenate dehydrogenase activities coeluted following ion-exchange chromatography, suggesting their identity as catalytic properties of a single broad-specificity cyclohexadienyl dehydrogenase. Each dehydrogenase activity was inhibited by 4-hydroxyphenylpyruvate, but not by L tyrosine. Two aromatic aminotransferases were resolved, one preferring the L phenylalanine:2-ketoglutarate substrate combination and the other preferring the L-tyrosine: 2-ketoglutarate substrate combination. Each aminotransferase was also able to transaminate prephenate. The overall picture of regulation is one in which L-tyrosine modulates L-phenylalanine synthesis via activation of prephenate dehydratase. L-Phenylalanine in turn regulates early-pathway flow through inhibition of DAHP synthase. The recent phylogenetic positioning of N. gonorrhoeae makes it a key reference organism for emerging interpretations about aromatic-pathway evolution. PMID- 2894823 TI - [APUD cells in gastric cancer]. AB - Endocrine cells (APUD cells) of digestive mucosa can be source of neoplasias, usually called "carcinoids". Nevertheless, there are some reports in literature about the presence of APUD cells in carcinomas as a tumor component. However, these tumors seem to have not the biological and clinical behavior of carcinoids. These types of neoplasias have been reported mainly in stomach and colon. In the present work, the frequency of APUD cells was studied in 42 gastric carcinomas. Argyrophil cells were observed in six cases (14.3%) and argentaffin cells in one (2.3%); their histopathological pattern were well differentiated adenocarcinoma (5) and "signet ring cell carcinoma" (1). The APUD cell distribution and number in these neoplasias were quite irregular in each case examined and in different areas of the same case. PMID- 2894824 TI - Effects of Bordetella avium on lymphoid tissue monoamine concentrations in turkey poults. AB - Six hours post-hatch, large white turkey poults were inoculated intranasally with 5 x 10(7) cells of the W isolate of Bordetella avium. Three hours after inoculation and subsequently on days 7, 10, 14, 21, and 28 postinoculation, poults from infected and control groups were killed by cervical dislocation. Thymus, spleen, and bursa of Fabricius were removed, weighed, and frozen until assayed for norepinephrine (NE), dopamine (DA), and serotonin (5HT). B. avium infection caused a reduced concentration of NE, DA, and 5HT in the spleen, thymus, and bursa of Fabricius. The reduced concentrations of these monoamines in lymphoid tissues of diseased poults may be a normal response during the course of a disease or during the mounting of an immune response. PMID- 2894826 TI - Experimentally induced necrotic enteritis in chickens. AB - A 1.3 to 10% incidence of necrotic enteritis was experimentally produced in broiler-type chickens in three of five trials. The incidence range observed was considerably narrower and lower than the 5.6-37.3% range reported in the literature. Clostridium perfringens was inconsistently isolated from the liver and intestine of dosed chickens. PMID- 2894825 TI - Antigenic relatedness and partial amino acid sequences of pili of Escherichia coli serotypes O1, O2, and O78 pathogenic to poultry. AB - Pilus proteins from Escherichia coli serotypes O1, O2, and O78 pathogenic to poultry were compared with regard to their antigenic relatedness and partial amino acid sequences. Agglutination, immunodiffusion, and immunoblot assays with polyclonal antibodies to these pili showed that these pili not only share some common antigens but also contain antigens unique to each pilus. The partial amino terminal amino acid sequences support our earlier findings that the pili are different but contain some structural homologies. PMID- 2894827 TI - Physical exercise and the neuroendocrine control of reproduction. AB - Reproductive change during conditioning exercise (physical training provides a model of hypothalamic adaptation to alterations in the external and internal environment. Parallels exist between the reproductive changes with exercise and those occurring with physical illness, undernutrition and psychological trauma. Although menstrual cyclicity may be disrupted in younger women, luteal phase shortening, anovulation and decreased premenstrual symptoms within normal ovulatory cycles are the most frequent observations noted. Baseline LH, prolactin and oestradiol tend to be lower, and other hormones unchanged, in trained women. Testosterone may be decreased within the normal range in men. Recent evidence shows that LH pulse frequency, amplitude and area under the LH curve are decreased in both female and male runners. Interrelationships between increases in central dopamine, endorphin and probably some hypothalamic message(s) relating to nutritional state appear to modulate these reproductive changes. The clinical and therapeutic response to reproductive alterations in the context of exercise differs when these are seen as adaptive and not as disease processes (Prior and Vigna, 1985b). PMID- 2894828 TI - Dissimilar effects of 1-oleoyl-2-acetylglycerol and phorbol 12-myristate 13 acetate on fatty acid synthesis in isolated rat-liver cells. AB - Exogenous 1-oleoyl-2-acetylglycerol (OAG) is known to mimic the action of tumour promoting phorbol esters in various cell types. However, in isolated rat hepatocytes OAG depressed the rate of de novo fatty acid synthesis and the activity of the key enzyme acetyl-CoA carboxylase (EC 6.4.1.2), in contrast to the pronounced stimulation of both parameters by phorbol 12-myristate 13-acetate (PMA). The inhibition by OAG appeared to be dose- and time-dependent. On the other hand, medium-chain 1,2-diacylglycerols like 1,2-dioctanoyl-sn-glycerol did mimic the stimulatory action of PMA. The anomalous effect of OAG may well be explained by its metabolic breakdown leading to liberation of oleate and subsequent inhibition of acetyl-CoA carboxylase activity by endogenously formed oleoyl-CoA. The stimulatory effects of both PMA and medium-chain diacylglycerols are likely to be mediated by protein kinase C. PMID- 2894829 TI - Isolation of mutants of Schizosaccharomyces pombe unable to synthesize cadystin, small cadmium-binding peptides. AB - Schizosaccharomyces pombe synthesize small cadmium-binding peptides cadystin, structure of which is (gamma-Glu-Cys)n-Gly, in response to cadmium. Mutants unable to synthesize cadystin were found in the mutants hypersensitive to cadmium. Some of them lack activity of either gamma-glutamylcysteine synthetase (EC 6.3.2.2) or glutathione synthetase (EC 6.3.2.3), enzyme involved in glutathione biosynthesis. Some mutants have the same activity levels of these enzymes as wild type has. These results indicate that some steps of cadystin biosynthesis are catalyzed by the enzymes catalyzing glutathione biosynthesis. PMID- 2894830 TI - Prosomatostatin processing in anglerfish brain, gut and pancreas. AB - The distribution of somatostatin immunoreactive forms in three tissues of the anglerfish (Lophius piscatorius L.) was analyzed by a combination of gel permeation, High Pressure Liquid Chromatography and amino acid analysis. The data indicate that prosomatostatins I and II are expressed in both neural and gastro intestinal tissues and that their post-translational processing gives rise to somatostatin-14 I, somatostatin-28 II and to some of its hydroxylysine23 derivative, respectively. It is concluded that, in contrast to the mammals, production of two somatostatins in the Teleostean fish requires two structurally distinct precursors whose processing operates in a fixed pattern rather than in a tissue-specific manner. PMID- 2894831 TI - Sequence of the genes for the beta and epsilon subunits of the ATP synthase of Bacillus megaterium QM B1551. AB - Four of the genes for the subunits of the proton-translocating ATPase of Bacillus megaterium have been cloned into pBR322. Previous studies have shown that two of these genes, for the alpha and beta subunits, can complement Escherichia coli mutants defective in the genes for those subunits (Hawthorne, C.A., and Brusilow, W.S.A. 1985. J. Biol. Chem. 261, 5245-5248). We report here a restriction map of the cloned region and the complete nucleotide sequence of the genes for the beta and epsilon subunits as well as the deduced amino acid sequences and molecular weights of those subunits. PMID- 2894832 TI - Functional cholesteryl binding agents: evaluation of viability and specificity of antibodies bound to modified phospholipid vesicles. AB - A cholesterol derivative was incorporated into small unilamellar phospholipid vesicles, and antibodies were bound covalently to the vesicles. More than one antibody was bound to each vesicle. The antigen binding viability and specificity were determined using a modified radioimmunoassay and an in vitro cell assay. Both of these tests showed good antibody activity and specificity. The antigen affinity of the bound antibodies was higher than for the unbound antibody due to more than one viable antibody being bound to each vesicle. The modified vesicles can be used as immunodirected drug delivery systems for both diagnosis and therapy. PMID- 2894834 TI - [Short stature in a case of HTLV-I-associated myelopathy with juvenile onset]. PMID- 2894833 TI - Clostridial septic arthritis: case report and review of the literature. AB - We describe a patient who had septic arthritis caused by Clostridium perfringens. Clostridial organisms are very uncommon causes of septic arthritis. Only 13 cases have been reported previously. The diagnosis should be suspected in patients with a history of penetrating joint trauma and in immunocompromised patients. Successful treatment has usually consisted of surgical synovectomy in combination with high-dose intravenous penicillin therapy. Multiple aspirations of affected joints as a definitive treatment should be used with caution and only in patients who are not candidates for surgery. PMID- 2894835 TI - Polyclonal integration of HTLV-I proviral DNA in lymphocytes from HTLV-I seropositive individuals: an intermediate state between the healthy carrier state and smouldering ATL. AB - We have studied 15 individuals (aged 14-74 years) with antibodies to HTLV-I in their serum and random integration of HTLV-I proviral DNA in their peripheral blood lymphocytes. All but one of these patients suffered from a variety of non specific complaints which did not correspond to those of adult T-cell leukemia (ATL). All of them were born in Kyushu and Okinawa which are endemic areas for HTLV-I infection; 25% of their family members were also seropositive for HTLV-I. The only haematological abnormality in these patients was the presence of few atypical lymphoid cells in the peripheral blood. The CD4/CD8 ratios were normal but the proportion of Tac positive cells was slightly higher than normal. These individuals with polyclonal integration of HTLV-I proviral DNA seem to represent an intermediate state between smouldering ATL (monoclonal integration) and healthy HTLV-I carriers (with antibodies but no detectable HTLV-I proviral DNA). Patients with this intermediate state of HTLV-I infection may be at risk to progress to ATL. The natural history of HTLV-I infection in humans leading to the development of ATL is reviewed in the light of these new findings. PMID- 2894836 TI - Use of minisatellite DNA probes for recognition and characterization of relapse after allogeneic bone marrow transplantation. AB - Restriction fragment length polymorphisms can be used to distinguish blood and marrow cells from close relatives. We used two probes that recognize a series of dispersed and highly polymorphic tandem-repetitive minisatellite regions in the human genome that can be detected via a shared 10-15 base pair core sequence similar to the generalized recombination sequence (chi) of E. coli. We have studied the resulting individual-specific DNA fingerprints in 15 patients before and after allogeneic bone marrow transplantation performed for chronic myeloid leukaemia and in two patients transplanted for acute leukaemia. Early engraftment could be demonstrated at 3 weeks post-transplant based on the recognition of cells of donor origin. One patient who failed to engraft had only recipient type marrow cells 3 months post-transplant. Nine patients who relapsed after transplantation had only cells of recipient origin. In one patient who relapsed after transplantation with T-cell depleted donor marrow, fractionation studies showed that his T-cells at relapse were of recipient origin. We conclude that these minisatellite probes are valuable for characterizing the origin of different cell populations after marrow transplantation and could be useful for characterizing relapse when donor and recipient are of the same sex. PMID- 2894837 TI - von Willebrand disease investigated by two novel RFLPs. AB - Two partial cDNAs for von Willebrand factor (vWF) were used to investigate gene lesions and restriction fragment length polymorphisms (RFLPs) in vW disease (vWd) and normal controls. No gene alteration was detected but two TaqI RFLPs, likely to be intronic and originating from point mutations, were found in the 3' part of vWF gene. The two TaqI RFLPs, identified by the same probe, are informative in approximately 50% of the subjects. Used in combination with two other known RFLPs, they define several haplotypes similarly distributed in vWd and normals. Linkage disequilibrium between loci identified by the RFLPs is present. In a family study the RFLP patterns demonstrate homozygosity for the affected vWF gene in a severe (type III) patient and identify several heterozygous subjects. The RFLPs analysis has been related to the haemostatic values and multimer distribution. In two of the four unrelated patients with severe vWd examined the RFLPs study indicates double heterozygosity for the affected vWF genes. PMID- 2894838 TI - Increased uterine prostaglandin E receptors in menorrhagic women. AB - PGE receptor concentrations were measured in myometrial samples collected from 10 women at hysterectomy. Five women had normal measured menstrual blood loss (35-44 ml) and the remainder had unexplained menorrhagia occurring in the absence of any uterine, pelvic or general pathology, with losses ranging from 85 to 925 ml. Median PGE receptor concentrations were significantly higher in the women with menorrhagia (1077 fmol/mg protein) than in the women with normal menstrual blood loss (625 fmol/mg protein) and correlated with menstrual blood loss (P less than 0.02). These findings suggest that unexplained menorrhagia may simply be a constitutional variant in some women and that specific and potent PGE uterine receptor antagonists would furnish effective non-surgical treatment for unexplained menorrhagia. PMID- 2894839 TI - Radiotherapy of periocular basal cell carcinomas: recurrence rates and treatment with special attention to the medical canthus. AB - Basal cell carcinomas of the eyelids, especially those in the medial canthal area, may cause extensive local destruction. Recurrent tumours are more aggressive and become progressively more difficult to treat; this is especially true for postirradiated recurrent, medial canthal, basal cell carcinomas. Tumours in this area should thus be treated by a technique which allows tissue sampling in order to gauge the adequacy of the treatment, with the goal being complete extirpation of the tumour. Excision monitored by frozen section control or Mohs' surgery is our recommendation based on a retrospective analyses of 631 eyelid basal cell carcinomas, half of which were primary tumours and half recurrent. PMID- 2894840 TI - Gene structure of cytochrome P-450(M-1) specifically expressed in male rat liver. AB - Cytochrome P-450(M-1) [P-450(M-1)] is specifically expressed in adult male rat liver [Yoshioka, H., Morohashi, K., Sogawa, K., Miyata, T., Kawajiri, K., Hirose, T., Inayama, S., Fujii-Kuriyama, Y., & Omura, T. (1987) J. Biol. Chem. 262, 1706 1711]. Isolation and analysis of the gene for P-450(M-1) revealed that the coding region of the gene is interrupted by eight introns and is dispersed over a 35 kilobase pair region of chromosomal DNA. Intron insertion sites of the P-450(M-1) gene are located at equivalent positions to those of cytochrome P-450b and P 450e, which are phenobarbital-inducible. Sequence analysis of the 5'-upstream region of the P-450(M-1) gene shows that there is a homologous sequence to glucocorticoid regulatory elements (GRE) identified in glucocorticoid-responsive genes. PMID- 2894841 TI - The unusual enzymology of ATP synthase. PMID- 2894842 TI - Construction of an altered proton donation mechanism in Escherichia coli dihydrofolate reductase. AB - We have explored the substrate protonation mechanism of Escherichia coli dihydrofolate reductase by changing the location of the proton donor. A double mutant was constructed in which the proton donor of the wild-type enzyme, aspartic acid-27, has been changed to serine and simultaneously an alternative proton donor, glutamic acid, has replaced threonine at position 113. The active site of the resulting variant enzyme molecule should therefore somewhat resemble that proposed for the R67 plasmid-encoded dihydrofolate reductase [Matthews, D. A., Smith, S. L., Baccanari, D. P., Burchall, J. J., Oatley, S. J., & Kraut, J. (1986) Biochemistry 25, 4194]. At pH 7, the double-mutant enzyme has a 3-fold greater kcat and an unchanged Km(dihydrofolate) as compared with the single mutant Asp-27----Ser enzyme described previously [Howell, E. E., Villafranca, J. E., Warren, M. S., Oatley, S. J., & Kraut, J. (1986) Science (Washington, D.C.) 231, 1123]. Additionally, its activity vs pH profiles together with observed deuterium isotope effects, suggest that catalysis depends on an acidic group with a pKa of 8. It is concluded that the dihydropteridine ring of a bound substrate molecule can indeed be protonated by a glutamic acid side chain at position 113 (instead of an aspartic acid side chain at position 27), but with greatly decreased efficiency: at pH 7, the double mutant still has a 25-fold lower kcat (1.2 s-1) and a 2900-fold lower kcat/km(dihydrofolate) (8.6 X 10(3) s-1 M-1) than the wild-type enzyme. PMID- 2894843 TI - ATP synthase from bovine mitochondria: sequences of imported precursors of oligomycin sensitivity conferral protein, factor 6, and adenosinetriphosphatase inhibitor protein. AB - Oligomycin sensitivity conferral protein (OSCP), factor 6 (F6), and ATPase inhibitor protein are all components of the ATP synthase complex of bovine mitochondria. They are encoded in nuclear DNA. Complementary DNA clones encoding the precursors of these proteins have been isolated from a bovine library by using mixtures of synthetic oligonucleotides as hybridization probes, and their DNA sequences have been determined. The deduced protein sequences show that the OSCP, F6, and inhibitor proteins have N-terminal presequences of 23, 32, and 25 amino acids, respectively. These presequences are not present in the mature proteins. It is assumed that they serve to direct the proteins into the mitochondrial matrix. The cDNA clones have also been employed as hybridization probes to investigate the genetic complexity of the three proteins in cows and humans. These experiments indicate that the bovine and human inhibitor and bovine F6 proteins are encoded by single genes but suggest the possibility of the presence in both species of more than one gene (or pseudogenes) for the OSCP. PMID- 2894844 TI - Mitochondrial ATP synthase: dramatic Mg2+-induced alterations in the structure and function of the F1-ATPase moiety. AB - The ATPase activity of the F1 moiety of rat liver ATP synthase is inactivated when incubated prior to assay at 25 degrees C in the presence of MgCl2. The concentration of MgCl2 (130 microM) required to induce half-maximal inactivation is over 30 times higher than the apparent Km (MgCl2) during catalysis. Moreover, the relative efficacy of divalent cations in inducing inactivation during prior incubation follows an order significantly different from that promoting catalysis. Inactivation of F1-ATPase activity by Mg2+ is accompanied by the dramatic dissociation from the F1 complex of alpha subunits and part of the gamma subunit population. The latter form a precipitate while the beta, delta, and epsilon subunits, and the remaining part of the gamma-subunit population, remain soluble. Dissociation is not a sudden "all or none" event but parallels loss of ATPase activity until alpha subunits have almost completely dissociated together with about 50% of the gamma-subunit population. Mg2+-induced loss of F1-ATPase activity cannot be prevented by including either the hydrolytic substrates ATP, GTP, or ITP in the incubation medium or the product ADP. Ethylenediaminetetraacetic acid, mercaptoethanol, and dithiothreitol are also ineffective in preventing loss of ATPase activity. Significantly, KPi at high concentration (greater than or equal to 200 mM) is effective in partially protecting F1 against inactivation. However, the most effective means of preventing Mg2+-induced inactivation of F1-ATPase activity is to rebind F1 to its F0 moiety in F1-depleted particles. When bound to F0, F1 is protected completely against divalent cation induced inactivation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894845 TI - Identification of nonprotein ligands to the metal ions bound to glutamine synthetase. AB - Electron paramagnetic resonance (EPR) was used to study the environment of Mn2+ bound to the tight (n1) metal ion binding site of glutamine synthetase in the presence of analogues of the tetrahedral adduct, L-methionine (S)-sulfoximine [Met(O)(NH)-S] and L-methionine (R)-sulfoximine [Met(O)(NH)-R]. The Mn2+ EPR spectrum in the presence of Met(O)(NH)-S is identical with the previously published spectrum obtained from a mixture of isomers [Met(O)(NH)-RS] [Villafranca, J. J., Ash, D. E., & Wedler, F. C. (1976) Biochemistry 15, 544] and is characteristic of a highly octahedral metal ion environment with a small zero field splitting. The presence of Met(O)(NH)-R produces an EPR spectrum that appears characteristic of a more distorted metal ion environment, with a larger zero field splitting. These data demonstrate that the two isomers interact differently with the enzyme-bound Mn2+. Broadening of the Mn2+ EPR spectrum in the presence of Met(O)(NH) is observed in 17O-enriched water due to superhyperfine coupling of water to the metal ion. Deconvolution of the spectrum demonstrates the presence of at least a single water molecule in the inner coordination sphere of the metal ion. Superhyperfine coupling due to the 14N nucleus of the imine nitrogen of the sulfoximine moiety of Met(O)(NH)-S but not of Met(O)(NH)-R has been detected by electron spin-echo envelope modulation spectroscopy. Two intense peaks are evident in the presence of Met(O)(NH)-S with frequencies at 1.7 and 3.3 MHz. These peaks are absent when [15N]imine-labeled Met(O)(NH) is used, indicating the presence of the sulfoximine nitrogen of Met(O)(NH)-S in the inner coordination sphere of the metal ion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894846 TI - Characterization of three-subunit chloroplast coupling factor. AB - The delta- and epsilon-polypeptides were removed from chloroplast coupling factor 1 (CF1). The resulting enzyme, CF1(-delta, epsilon), is a stable active ATPase containing only alpha-, beta-, and gamma-polypeptides. The dependence of the steady-state kinetics of ATP hydrolysis catalyzed by CF1(-delta, epsilon) on the concentrations of ATP and ADP was found to be essentially the same as by activated CF1. Nucleotide binding studies with CF1(-delta, epsilon) revealed three binding sites: a nondissociable ADP site (site 1), a tight MgATP binding site (site 2), and a site that binds ADP and ATP with a dissociation constant in the micromolar range (site 3). Similar results have been obtained with CF1. For both CF1 and CF1(-delta, epsilon), the binding of MgATP at site 2 is tight only in the presence of Mg2+. Fluorescence resonance energy transfer was used to map distances between the gamma-sulfhydryl ("dark" site) and gamma-disulfide and between the gamma-sulfhydryl and the three nucleotide sites. These distances are within 5% of the corresponding distances on CF1. These results indicate that removal of the delta- and epsilon-polypeptides from CF1 does not cause significant changes in the structure, kinetics, and nucleotide binding sites of the enzyme. PMID- 2894847 TI - Estimation of the turnover number of bovine heart F0F1 complexes for ATP synthesis. AB - In mitochondria and submitochondrial particles (SMP), the rate of ATP synthesis is restricted by the rate of energy production by the respiratory chain. Fractional inactivation of the ATP synthase complexes (F0F1) of bovine heart SMP by covalent modifiers increased the rate of ATP synthesis per mole of active F0F1. Thus, by use of SMP containing fractionally inactivated F0F1 complexes, a synthetic rate of 420 mol of ATP (mol of F0F1.s)-1 was measured, which extrapolated to a Vmax of 440 s-1. At this extrapolated point, the turnover rate of F0F1 complexes was independent of the rate of energy production by the respiratory chain. These results have been discussed in relation to the effect of fractional inactivation of the F0F1 complexes of SMP on the steady-state free energy of the system. The above rate of ATP synthesis is comparable to the rate of ATP hydrolysis by SMP (400-520 s-1) in the absence of energy coupling constraints and control by the ATPase inhibitor protein. More interestingly, this rate is also comparable to the rate of ATP synthesis by chloroplast F0F1 under high light intensity (approximately 420 s-1). Under the conditions specified, bovine heart SMP and chloroplasts show similar apparent Km values for ADP. Thus, it appears that the mammalian and chloroplast ATP synthase complexes are similar not only in structure but also in catalytic efficiency for ATP synthesis. PMID- 2894848 TI - Transcriptional and posttranscriptional regulation of tyrosine aminotransferase by insulin in rat hepatoma cells. AB - The molecular mechanisms of induction of tyrosine aminotransferase (TAT) by insulin were studied in the well-differentiated rat hepatoma cell line Fao. Incubation of Fao cells with insulin resulted in a 2-fold increase in TAT activity and TAT mRNA measured by Northern blot analysis with an oligonucleotide probe to the 5' end of the gene. The effect of insulin on TAT activity had a lag period of 30-60 min and was maximal within 4-5 h. The insulin effect on TAT mRNA was rapid, half-maximal after 15 min, and complete within 1-2 h. Insulin dose response curves for stimulation of TAT activity and TAT mRNA were almost identical. TAT mRNA levels and enzyme activity were also stimulated by anti insulin receptor antibodies and dexamethasone but not by wheat germ agglutinin, concanavalin A, or phytohemagglutin. The effect of insulin on the TAT gene was further investigated by measuring the relative rate of transcription in isolated nuclei using genomic TAT clones. Insulin produced a 1.5-1.7-fold increase in the production of TAT RNA transcripts. Dexamethasone induced both TAT activity and TAT mRNA to a comparable extent. In the presence of dexamethasone, insulin produced an additional 2-fold stimulation of TAT activity but had no additional effect on the abundance of TAT mRNA. These data provide direct evidence that insulin can increase TAT activity by at least two distinct mechanisms: insulin alone appears to increase TAT activity and TAT mRNA due to a stimulation of the TAT gene transcription rate; while in the presence of glucocorticoids, insulin increases TAT activity but not TAT mRNA, suggesting an insulin effect at the posttranscriptional level. PMID- 2894850 TI - Structure-function relationships of the Escherichia coli ATP synthase probed by trypsin digestion. AB - Trypsin cleavage has been used to probe structure-function relationships of the Escherichia coli ATP synthase (ECF1F0). Trypsin cleaved all five subunits, alpha, beta, gamma, delta, and epsilon, in isolated ECF1. Cleavage of the alpha subunit involved the removal of the N-terminal 15 residues, the beta subunit was cleaved near the C-terminus, the gamma subunit was cleaved near Ser202, and the delta and epsilon subunits appeared to be cleaved at several sites to yield small peptide fragments. Trypsin cleavage of ECF1 enhanced the ATPase activity between 6- and 8 fold in different preparations, in a time course that followed the cleavage of the epsilon subunit. This removal of the epsilon subunit increased multisite ATPase activity but not unisite ATPase activity, showing that the inhibitory role of the epsilon subunit is due to an effect on cooperativity. The detergent lauryldimethylamine oxide was found to increase multisite catalysis and also increase unisite catalysis more than 2-fold. Prolonged trypsin cleavage left a highly active ATPase containing only the alpha and beta subunits along with two fragments of the gamma subunit. All of the subunits of ECF1 were cleaved by trypsin in preparations of ECF1F0 at the same sites as in isolated ECF1. Two subunits, the beta and epsilon subunits, were cleaved at the same rate in ECF1F0 as in ECF1 alone. The alpha, gamma, and delta subunits were cleaved significantly more slowly in ECF1F0.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894849 TI - Beta subunit of rat liver mitochondrial ATP synthase: cDNA cloning, amino acid sequence, expression in Escherichia coli, and structural relationship to adenylate kinase. AB - The amino acid sequence of all but a few N-terminal residues of the beta subunit of rat liver ATP synthase has been determined from cDNA clones. Rat liver F1-beta is shown to contain 17 amino acid differences from that reported for F1-beta of bovine heart, 2 differences of which involve differences in charge. This may account in part for the observation that bovine heart F1 binds nucleotides with much greater affinity than the rat liver enzyme. Rat liver F1-beta also contains homologous regions with another nucleotide binding protein, adenylate kinase, for which high-resolution structural studies are available. Adjacent to one of these homologous regions is an eight amino acid stretch which bears striking homology to the phosphorylation region of the (Na+,K+)-ATPase. The combination of these two homology regions may constitute at least part of a nucleotide binding domain in F1-beta. Significantly, both rat liver and bovine heart beta contain these regions of homology, whereas the 17 amino acid differences between the two enzymes lie outside this region. The possibility of a second nucleotide binding domain which differs between the two enzymes is discussed. A cDNA clone containing all the regions of homology as well as 11 of the 17 amino acid differences between the bovine heart and rat liver beta subunits has been ligated into the bacterial expression vector pKK223-3. After transformation of a protease deficient strain of Escherichia coli, this cDNA clone is expressed as a 36 kilodalton protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894852 TI - Kinetics of the release of the mitochondrial inhibitor protein. Correlation with synthesis and hydrolysis of ATP. AB - (1) The kinetics of the release of the mitochondrial inhibitor protein (IF1) is studied in bovine heart submitochondrial vesicles supplemented with 125I-labelled IF1, using a method for rapidly 'freezing' the state of F1-IF1 interaction. It is shown that generation of a protonmotive force leads to release of IF1 from F1 into solution, following an exponential process. (2) In one set of experiments the rate of IF1 release, in IF1 supplemented vesicles generating a protonmotive force, is correlated with the induction of ATP hydrolytic capacity. It is found that, even under different metabolic states (phosphorylating and non phosphorylating conditions), both processes follow the same time-course (half time of around 40 s) and that there is a direct correlation between induced ATPase capacity and IF1 released. This finding rules out the possibility of a non inhibitory binding site for IF1 on the membrane. (3) In a second set of experiments, also using IF1 supplemented vesicles, the induction of the ATP hydrolytic capacity after energisation is correlated with the induction of the ATP synthetic capacity. Initial rates of both processes are monitored using firefly luciferase, keeping the assay systems as similar as possible. It is shown that the induction of each capacity follows an exponential time-course, with a half-time of around 40 s. This is in good agreement with the half-times obtained for the induction of ATP hydrolytic capacity and the rate of IF1 release, using the quench-stop method. (4) If the induction of ATP hydrolytic and synthetic capacities is followed in untreated submitochondrial vesicles, i.e., vesicles not supplemented with IF1, the extent and time-course of the change in both hydrolytic and synthetic capacities remain correlated, but the half-time of the transient falls to around 10 s. It is suggested that the length of the transient, observed in IF1 supplemented vesicles, results from partial loss of coupling during repeated centrifugations. (5) These results demonstrate that energy dependent release of IF1 from F1 into solution results in a concomitant increase in both ATP synthetic and hydrolytic capacities of the ATP synthase complex, and that the time-course of this process is sensitive to the degree of coupling of the vesicles. PMID- 2894851 TI - Heparin cofactor II: cDNA sequence, chromosome localization, restriction fragment length polymorphism, and expression in Escherichia coli. AB - Heparin cofactor II (HCII) is an inhibitor of thrombin in plasma that is activated by dermatan sulfate or heparin. An apparently full-length cDNA for HCII was isolated from a human liver lambda gt11 cDNA library. The cDNA consisted of 2215 base pairs (bp), including an open-reading frame of 1525 bp, a stop codon, a 3'-noncoding region of 654 bp, and a poly(A) tail. The deduced amino acid sequence contained a signal peptide of 19 amino acid residues and a mature protein of 480 amino acids. The sequence of HCII demonstrated homology with antithrombin III and other members of the alpha 1-antitrypsin superfamily. Blot hybridization of an HCII probe to DNA isolated from sorted human chromosomes indicated that the HCII gene is located on chromosome 22. Twenty human leukocyte DNA samples were digested with EcoRI, PstI, HindIII, KpnI, or BamHI, and Southern blots of the digests were probed with HCII cDNA fragments. A restriction fragment length polymorphism was identified with BamHI. A slightly truncated form of the cDNA, coding for Met-Ala instead of the N-terminal 18 amino acids of mature HCII, was cloned into the vector pKK233-2 and expressed in Escherichia coli. The resultant protein of apparent molecular weight 54,000 was identified on an immunoblot with 125I-labeled anti-HCII antibodies. The recombinant HCII formed a complex with 125I-thrombin in a reaction that required the presence of heparin or dermatan sulfate. PMID- 2894853 TI - The binding and release of the inhibitor protein are governed independently by ATP and membrane potential in ox-heart submitochondrial vesicles. AB - (1) The effects of membrane potential (delta psi) and nucleotides on the interaction between the F1-ATP synthase and its natural inhibitor protein (IF1) are studied in ox-heart submitochondrial vesicles. (2) Membrane potential causes displacement of IF1 from submitochondrial vesicles, as shown by measuring both delta psi-dependent stimulation of ATPase capacity and release of 125I-labelled IF1 from the vesicles. These effects are abolished if ATP is included in the incubation. (3) There is a linear increase in the steady-state ATPase capacity of oxidising vesicles as delta psi is increased from 100 mV to 135 mV. Increasing delta psi above 140 mV leads to no further change. (4) At a constant membrane potential, ATP suppresses the increase in ATPase capacity, with a concentration for half maximal effect of 140 microM. This value is close to the Km for ATP hydrolysis by membrane-bound F1. This suppression is related to ATP concentration rather than to delta Gp or ATP/ADP ratio. (5) The unidirectional on- and off rates of IF1 were measured separately. The off-rate of IF1 is increased by membrane potential but unaffected by ATP. The on-rate, conversely, is increased by ATP. Thus, the suppression of the potential-dependent net release of IF1 from submitochondrial vesicles by ATP results from an increase of the IF1 on-rate above the off-rate. PMID- 2894854 TI - Sequence and over-expression of subunits of adenosine triphosphate synthase in thermophilic bacterium PS3. AB - The primary structures of all the subunits of thermophilic ATP synthase were determined, and its alpha, beta and gamma subunits could be over-expressed in Escherichia coli, because these subunits were stable and reconstitutable. DNA of 7500 base pairs in length was found to contain a cluster of nine genes for subunits of ATP synthase. The order of their reading frames (size in base pairs) was: I(381): a(630): c(216): b(489): delta(537): alpha(1507): gamma(858): beta(1419): epsilon(396), I being a gene for a small hydrophobic, basic protein expressed in vitro. All the termini of TF0F1 subunits were confirmed by peptide sequencing. Large quantities of the overexpressed thermophilic alpha, beta and gamma subunits were prepared from the extract of E. coli, by a few purification steps. PMID- 2894855 TI - Site-directed mutagenesis of stable adenosine triphosphate synthase. AB - Evidence was obtained that four ionizable residues in the alpha and beta subunits of thermophilic ATP synthase (TF0F1), corresponding to Lys-21 and Asp-119 in the MgATP binding segments of adenylate kinase, are essential for the normal catalytic activity. TF0F1 was used because it is the only ATP synthase whose alpha-, beta- and gamma-subunits can be reassembled into an active complex in the absence of both ATP and Mg. Lys-164 and Asp-252 of its beta-subunit were modified to isoleucine and asparagine, respectively, by site-directed mutagenesis using a multifunctional plasmid, and these genes were over-expressed in Escherichia coli. The resulting beta I164 and beta N252 subunits were both noncatalytic after re assembly into the alpha beta gamma-complex, even though both subunits bound significant amounts of ADP. When Lys-175 and Asp-261 of the alpha-subunit were similarly replaced by isoleucine and asparagine, respectively, the resulting alpha I175 subunit reassembled weakly into an oligomer, while the alpha N261 subunit showed an increased dissociation constant for ADP and was reconstituted into an alpha beta gamma-complex that showed no inter-subunit cooperativity. PMID- 2894856 TI - Unique action of a modified weakly acidic uncoupler without an acidic group, methylated SF 6847, as an inhibitor of oxidative phosphorylation with no uncoupling activity: possible identity of uncoupler binding protein. AB - The potent weakly acidic uncoupler SF 6847 was modified by methylation of its phenolic OH group, and the effect of the resulting derivative, with no acid dissociable group, on oxidative phosphorylation in rat liver mitochondria was examined. The methylated SF 6847 did not induce uncoupling at up to 40 microM, while SF 6847 uncoupled oxidative phosphorylation completely at about 20 nM, indicating that the acid-dissociable group is essential for uncoupling. The O methylated SF 6847 at 20 microM did, however, inhibit state 3 respiration of mitochondria, although it did not inhibit electron-flow through the respiratory chain, ATPase activated by weakly acidic uncouplers or Pi-ATP exchange. At the same concentration, it also inhibited ATP synthesis in submitochondrial particles. These features are different from those of known inhibitors of oxidative phosphorylation. Thus, O-methylated SF 6847 is a unique inhibitor of oxidative phosphorylation. The possible identity of the uncoupler binding protein is discussed on the basis of these results. PMID- 2894857 TI - ATP hydrolysis induces variable porosity to mannitol in the mitochondrial inner membrane. AB - Osmotic titration of ATPase activity in rat liver mitochondria was consistent with enhanced porosity of the mitochondrial inner membrane to mannitol due to ATP hydrolysis even when endogenous respiration was inhibited by rotenone. The occluded ATPase activity, which exhibits osmotic activation with an optimum near isotonicity, depends both on the ATPase activity per se and on the activity of the ADP/ATP carrier. Purified ADP/ATP carrier incorporated into small, unilamellar liposomes was critically shown to exhibit dependence of its activity on the osmotic pressure differences across the membrane, with maximal activity corresponding to isotonicity, regardless of the actual internal tonicity. PMID- 2894858 TI - The definition of mitochondrial H+ ATPase assembly defects in mit- mutants of Saccharomyces cerevisiae with a monoclonal antibody to the enzyme complex as an assembly probe. AB - mit- mutants with genetically defined mutations in the mitochondrial structural genes of the H+-ATPase membrane subunits 6, 8 and 9 were analysed to determine the H+-ATPase assembly defects that resulted as a consequence of the mutations. These include mutants which do not synthesize one of the membrane subunits and mutants which can synthesize these subunits, but in an altered form. Protein subunits which can still be assembled to the defective H+-ATPase in these mutants were determined by immunoprecipitation using a monoclonal antibody to the beta subunit of the enzyme complex. The results suggest that the assembly pathway of the mitochondrially synthesized H+-ATPase subunits involves the sequential addition of subunits 9, 8 and 6 to a membrane-bound F1-sector. In addition to subunits of the F0- and F1-sectors, two other polypeptides (Mr = 18,000 and Mr = 25,000) are associated with the yeast H+-ATPase. These polypeptides were not observed in the immunoprecipitates obtained from mutants in which the F0-sector is not properly assembled. PMID- 2894859 TI - The effects of nitroprusside and putative agonists on guanylate cyclase activity in squid giant axons. AB - cGMP content of axoplasm from the giant axon of Loligo forbesi was investigated after subjecting the axon to various treatments. Repetitive electrical stimulation or depolarisation by high K+ caused no change in cGMP content. Glutamate and serotonin were also without effect. The nicotinic agonist carbachol (100 microM) increased cGMP levels by 90% (n = 5). A large transient elevation of cGMP content was evoked by external nitroprusside (10 nM-20 microM in intact axons. Nitroprusside injected into both extruded axoplasm and intact axons also increased cGMP content, the stimulation being considerably higher in intact axons where the axolemma was also present. Nitroprusside was also active in axons where the soluble cytoplasmic components were washed out by internal perfusion. PMID- 2894860 TI - Soluble tyrosine hydroxylase (tyrosine 3-monooxygenase) from bovine adrenal medulla: large-scale purification and physicochemical properties. AB - A new procedure that permits large-scale purification of tyrosine 3-monooxygenase (tyrosine hydroxylase) (L-tyrosine,tetrahydropteridine:oxygen oxidoreductase (3 hydroxylating), EC 1.14.16.2) from the cytosolic fraction of bovine adrenal medulla is described. The homogenous enzyme revealed a subunit Mr of 60,000 and a specific activity of 425 nmol.min-1.mg-1. The N-terminal amino-acid sequence (27 residues) revealed 89% homology with the human pheochromocytoma enzyme as deduced from its cDNA sequence. The pure enzyme contained 0.66 +/- 0.09 mol iron, 0.13 mol zinc and 0.62 +/- 0.04 mol phosphate per mol subunit of Mr = 60,000. A broad light absorption band with its maximum around 700 nm (epsilon 700 nm = 1.3 (mM monomer)-1.cm-1) explains its blue-green color. EPR spectra at 3.6 K revealed high-spin Fe(III) (S = 5/2) in an environment of nearly axial symmetry (g values at 7.2-6.7, 4.7-5.3 and 1.9-2.0). A close correlation was observed between the absorbance at 700 nm and the intensity of the axial type of EPR spectrum. The absorption peak at 700 nm is compatible with a ligand-to-iron charge-transfer transition as a result of catecholate coordination to the iron. Physicochemical studies suggest that the enzyme does not undergo such major substrate- or cofactor-induced conformational changes as have been reported for the related enzyme, phenylalanine hydroxylase. PMID- 2894861 TI - Subcellular localization of non-specific carboxylesterases, acylcarnitine hydrolase, monoacylglycerol lipase and palmitoyl-CoA hydrolase in rat liver. AB - The subcellular distribution and sidedness on the membranes of four chemically and genetically distinct esterases (esterases ES-3, ES-4, ES-8, ES-15) in rat liver was investigated using selective substrates. (1) Rat liver homogenate was divided into nine subcellular fractions by differential centrifugation techniques. The cell fractions were assayed for the enzymatic hydrolysis of acetanilide (ES-3), propanidid, palmitoyl-CoA and monopalmitoylglycerol (ES-4), methyl butyrate and octanoylglycerol (ES-8), and decanoylcarnitine (ES-15). With all substrates, the highest specific activities were found in the rough and smooth endoplasmic reticulum fractions. This localization of the esterases was confirmed by labelling the cell fractions with the specific, covalently binding inhibitor bis(4-nitro[14C]phenyl) phosphate. The enzymatic hydrolysis of the palmitoyl esters in differing cell fractions did not completely parallel that of propanidid. This confirms the well-known existence of palmitoyl-CoA hydrolases other than esterase ES-4. (2) Density gradient fractionations with crude mitochondria indicated that a low amount of at least one of these carboxylesterases was an integral part of these organelles too. (3) Proteinase treatment reduced the non-specific esterase activities as well as lipase activities versus dioctanoylglycerol, acylcarnitines and palmitoyl-CoA only in detergent-disrupted microsomal vesicles. This might indicate a lumenal orientation of these enzymes. However, of the charged substrates palmitoylcarnitine and palmitoyl-CoA only the latter one showed the typical latency to be expected for a hydrolysis in the lumen of the endoplasmic reticulum. PMID- 2894862 TI - Adrenergic receptor properties of hepatocytes from male and female rats. AB - alpha 1- and beta-adrenergic receptor properties of intact hepatocytes from adult male and female rats were evaluated in ligand binding studies using [3H]prazosin and [3H]CGP-12177 (4-(t-butylamino-2-hydroxypropoxy)-[5,7-3H]benzimidazole-2-one HCl), a hydrophilic beta antagonist. Prior work had suggested that the response of hepatocytes from males to alpha 1-adrenergic stimulation was greater than that of cells from females. However, little sexual difference in prazosin affinity, number of binding sites or kinetics of association/dissociation with the cells was found. Epinephrine, [3H]prazosin competition for binding sites on intact cells was performed at 2 degrees C and 80-90% of agonist sites remained in a high affinity state with an epinephrine Kd comparable to that previously found in glucose release and phosphorylase alpha activation studies. Agonist Kd inferred from these competition experiments also showed no sexual dimorphism. These data suggest that the greater rise in the concentration of cytosolic free calcium and release of 45Ca from cells of males in response to epinephrine stimulation is not due to male/female alpha 1-receptor differences but, rather, may be a function of the previously observed sexual difference in cell calcium metabolism. [3H]CGP binding to hepatocytes from females was stereospecific, saturable and identified a single, high affinity site. Comparable sites were not found on cells from males, however, [3H]CGP binding to crude membrane preparations from both sexes was identical. This suggests that the loss of hepatic beta-receptor function in the adult male is due to an inaccessibility of beta-receptors at the external surface of the plasma membrane of the intact cell. Further studies with other beta-receptor ligands are being carried out to confirm these initial findings. PMID- 2894864 TI - [2-Deoxyglucose as a tool for analyzing the humoral component of the cardiovascular reaction to stress]. AB - Blood pressure (BP), heart rate (HR), adrenaline (A) and noradrenaline (NA) effects of 2-desoxyglucose (500 mg/kg i.v.) were studied in conscious chronically instrumented wistar rats. A and NA contents in the blood were estimated by HPLC with electrochemical detection. In 15-40 minutes after 2-DG administration it was 13-16-fold increase in A content, 1.7-1.9-fold increase in NA content. At the same time BP fell by 5 mm Hg and HR fell by 100 beats/min. Atropine blocked bradycardia but had no effect on BP. It is concluded that high levels of endogenous A during stress are not responsible for cardiovascular responses usually observed. PMID- 2894863 TI - Effect of membrane flow on the capture of receptors by coated pits. Theoretical results. AB - Coated pits trap cell surface receptors and mediate their internalization. Once internalized, many receptors recycle back to the cell surface. When recycled receptors are inserted into the plasma membrane, they move until they are again trapped in coated pits. The mechanisms for moving receptors from their insertion sites to coated pits are unknown. Unaided diffusion as the transport mechanism is consistent with the observed kinetics of receptor recycling. Another candidate for the transport mechanism is convection. For receptors that recycle to random positions on the cell surface, or to restricted regions about coated pits, we assess the importance of convective flow in the transport of receptors to coated pits. First we consider local flows set up by the formation of coated pits and their transformation into coated vesicles. As coated pits form and round into coated vesicles, surrounding membrane is drawn inward, creating flows directed toward the coated pit centers. We show that unless the lifetime of a coated pit is very short, 10 s or less, such local flows have a negligible effect on the time it takes receptors to reach coated pits. We also show that they are unlikely to be the mechanism that keeps receptors that have reached coated pits trapped within coated pits until they are internalized. Finally we calculate the mean time tau for a diffusing receptor to reach a coated pit in the presence of membrane flow that is constant in magnitude and direction, as may occur on moving cells. We show that for typical membrane flow velocities, tau can be reduced significantly from its value in the absence of flow. For example, a velocity v = 2.8 micron/min cuts the mean transport time in half. PMID- 2894865 TI - [Interaction of psychotropic preparations with the synaptic membranes of the cerebral cortex in rats]. AB - Interaction of psychotropic drugs with synaptosomal membranes from rat brain cortex was investigated by fluorescent probes. The data obtained indicate that all studied drugs change the state of membrane's surface. Tranquilizers, unlike antidepressants and neuroleptics, decreased fluorescence of the probe. Neuroleptics, unlike other drugs, penetrated deeper into the membranes hydrophobic core. PMID- 2894866 TI - [Paradoxical correlations of the effectiveness of the intranasal and intraperitoneal administration of dermorphins in rats]. AB - The analgetic activity of dermorphin and its analogue A-2 was assessed by the tail-flick test. Following intraperitoneal administration at doses 5 mg/kg and above the peptides showed significant effects. After intranasal application of the peptides a significant effect was observed in the range of low doses 0.001 0.1 mg/kg. After intranasal application of high dermorphin doses (1 or 5 mg/kg) the analgetic activity decreased. The effect of analogue A-2 lasted longer after intranasal, than after intraperitoneal administration. It is assumed that the neurophysiological mechanisms of the analgetic activity of dermorphins depend on the route of their administration. PMID- 2894868 TI - [Semisyngeneic transplantation of hematopoietic cells of native and cultured embryonic liver]. AB - The protective ability and graft-versus-host (GVH) activity in parental strain hematopoietic fetal liver cells (FLC) transplanted to irradiated F1 hybrids were evaluated quantitatively. A 21-day survival of more than 80% of semi-syngeneic mouse recipients required the injection of 2-5 X 10(6) nucleated fetal liver cells (FLC). The same effect could be obtained with FLC cultivated for 4-15 days. 5 to 25 X 10(6) parental FLC were necessary to induce a considerable GVH mortality within 2-3 months after transplantation. Thus, the minimal cell doses of both native and cultivated FLC enough for the maximal protective effect have proved ineffective for the provocation of the fetal GVH disease. Hematopoietic cells from long-term FLC cultures had a low protective potential though they could contain high CFUs concentration. This discrepancy shows clearly that such polypotent precursors as CFUs have no ability to restore hematopoiesis, in other words they cannot be totipotent stem cells. PMID- 2894867 TI - [Assessment of the action of taktivin on different stages of T-lymphocyte maturation]. AB - Tactivin, the thymic hormone preparation, evokes some phenotype alterations in T cell precursors (elimination of SC-1 antigen and expression of Thy-1-antigen) and cortical thymocytes (a decrease in the number of thymocytes carrying PNA receptor) similar to those arising in T-cell differentiation. Tactivin induces PNA+ -thymocyte response to PHA action and increases PHA response to PNA- thymocytes. It is weakly mitogenic for T-cell precursors and PNA- -thymocytes. The data suggest that Tactivin may be used for the treatment of immune deficiencies with T-cell differentiation and function defects. PMID- 2894869 TI - [Effect of antidepressants on reverse neuromediator uptake by the synaptosomes in control and stressed rats]. AB - The influence of chemically different antidepressants on the uptake of 5-HT, dopamine and GABA by the rat brain synaptosomes was tested, using radioisotope technique in control and chronically stressed (14 days) animals. Drugs were more potent inhibitors of neurotransmitter uptake in synaptosomes of stressed animals, as compared to synaptosomes from control ones, the activity increasing proportionally to the changes in a particular uptake system. It is suggested that the drugs inhibit the uptake of neurotransmitters studied by changing the properties of synaptosomal membrane lipid bilayer. It is also evident that neurochemical properties of psychotropic drugs must be evaluated on the membranes from animals in the model of experimental psychopathology. PMID- 2894870 TI - [Ultrastructural characteristics of the localization of the enzymes of cyclic nucleotide metabolism in the mammalian brain]. AB - The enzymes involved in cyclic nucleotide turnover (adenylate cyclase, guanylate cyclase, phosphodiesterase) were located in various regions of the brain, in synaptosomes and isolated synaptic membranes, using electron cytochemical methods. The interaction of the above enzymes in the processes of adrenergic and cholinergic cell reception in the CNS are discussed. PMID- 2894871 TI - [Morphometry of the vesicular apparatus of the neuromuscular junction with different modes of transmitter release]. AB - Neuromuscular junctions in the diaphragm muscle of rats were studied, using a usual chemical fixation technique and quick prefreezing of the muscle. The number of synaptic vesicles in the vicinity of presynaptic membrane decreased significantly during synaptic function activation. Quantitative investigation of axon terminal vesicle apparatus revealed heterogeneity in the size of synaptic vesicle pool. The pattern of synaptic vesicle size distribution in different functional states of the synapse suggests that size heterogeneity reflects their functional peculiarities. PMID- 2894872 TI - Catecholamines released from the adrenal medulla exert a compensatory, protective effect at beta 2-adrenoceptors against Paf-induced death in mice. AB - 1. The effects of a number of drugs and experimental conditions, which inhibit or stimulate adrenergic function, were evaluated on platelet-activating factor (Paf) induced death in conscious mice. 2. Adrenalectomy markedly potentiated Paf toxicity, while guanethidine and reserpine did not. However, reserpine, which produced a virtually complete depletion of catecholamines (CA) in cardiac tissue, was not able to reduce adrenal CA by more than 58%. Drugs which release noradrenaline from the adrenergic nerve terminals, such as tyramine and amphetamine, did not protect mice from Paf toxicity, while drugs or conditions which favour the release of CA from the adrenal medulla, such as urethane and cold-induced stress, did. 3. beta 2- and beta 1 + beta 2-adrenoceptor antagonists (ICI 118551, propranolol and nadolol), but not beta 1-antagonists (atenolol, practolol, metoprolol and CGP 20712 A), potentiated Paf toxicity at low doses; beta 2- and beta 1 + beta 2-agonists (salbutamol, fenoterol and isoprenaline), but not beta 1-agonists (prenalterol and tazolol) were potent inhibitors of Paf toxicity. alpha 1- and alpha 2-adrenoceptor agonists and antagonists did not exert significant effects. Propranolol did not appear to enhance the hypotensive action of Paf in pentobarbitone-anaesthetized mice. 4. It is concluded that manipulation of the release of CA from the adrenal medulla, but not from adrenergic nerves, has profound effects on Paf toxicity in mice. A number of considerations support the hypothesis that bronchoconstriction is a major determinant of Paf-induced death in mice. PMID- 2894873 TI - Effect of dopamine antagonists on the urine flow of rats infused with hypotonic saline. AB - 1. The probable involvement of dopamine in the regulation of water excretion was investigated by administering dopamine antagonists intravenously to barbiturate- anaesthetized rats undergoing a water diuresis induced by the infusion of 0.83% glucose with 0.3% NaCl at the rate of 9 ml h-1. 2. Administration of 100 micrograms of the D1-/D2-dopamine antagonist, haloperidol, reduced the enhanced urine flow of rats infused with the hypotonic solution by 69% (from 75.4 +/- 13.0 to 23.6 +/- 6.0 microliter min-1, P less than 0.01). Similarly, the D1-receptor antagonist, SCH 23390, reduced urine flow by 58% (from 77.5 +/- 9.2 to 32.7 +/- 7.2 microliters min-1, P less than 0.01) and the D2-receptor antagonist, sulpiride, by 47% (from 66.2 +/- 8.6 to 35.1 +/- 6.8 microliter min-1, P less than 0.05). 3. The injection of SCH 23390 increased the urine osmolality from 189.6 +/- 27.5 to 479.8 +/- 45.8 mosm kg-1 (P less than 0.05). There was no significant change in sodium and potassium excretion in any of the experiments. Blood pressure (BP) decreased after haloperidol and SCH 23390 injection from control values of 121.7 +/- 1.7 and 116.5 +/- 7.4 to 113.3 +/- 3.3 and 106.0 +/- 8.8 mmHg respectively (P less than 0.05). 4. To study whether the influence of dopamine antagonists on urine flow during water diuresis depends on antidiuretic hormone (ADH), we administered 0.6 micrograms d(CH2)5-D-Phe-Ile-AVP (an ADH antagonist) shortly after the injection of 100 micrograms SCH 23390. The preferential V2 ADH-antagonist abolished the antidiuretic effect of SCH 23390 but did not affect its blood pressure reducing effect (from 118.6 +/- 5.6 to 103.2 +/ 4.6 mmHg, P <0.01). 5. These results suggest that dopamine antagonists blunted the hypotonic saline-induced diuresis by favouring ADH release through an interference with an inhibitory dopaminergic pathway. PMID- 2894874 TI - Cardiac and renovascular effects in the anaesthetized dog of BW A575C: a novel angiotensin converting enzyme inhibitor with beta-adrenoceptor blocking properties. AB - 1. In the anaesthetized open-chest dog, BW A575C (N-(1-(S)-carboxy-5-[4(3- isopropylamino-2-(R,S)-hydroxypropoxy)indole-2- carboxamido]pentyl)-(R,S)-alanyl (S)-proline) causes a dose-dependent inhibition of the isoprenaline response (increased cardiac rate). In this preparation BW A575C is approximately 50 times less active than propranolol, and 500 times less active than pindolol at the cardiac beta 1-adrenoceptor. 2. At equieffective cardiac beta 1-adrenoceptor blocking doses in the anaesthetized, open-chest dog, BW A575C (5.0 mg kg-1, i.v.) significantly reduces diastolic blood pressure and reduces cardiac contractility and rate. By contrast, propranolol (0.1 mg kg-1, i.v.) and pindolol (0.01 mg kg 1, i.v.) have little effect on diastolic blood pressure, but significantly reduce cardiac contractility and rate. The effects of BW A575C on cardiac rate are not significantly different from those of propranolol and pindolol, but its effects on cardiac contractility are significantly less than those of propranolol. BW A575C also produces some increase in left ventricular internal dimensions at end diastole. This small cardiac dilatation is not significantly different from that observed with pindolol but is significantly less than that of propranolol. 3. In the anaesthetized closed-chest dog, BW A575C causes a dose-dependent inhibition of the angiotensin I pressor response. In this preparation BW A575C is approximately equiactive with enalapril at preventing the pressor response due to conversion of exogenous angiotensin I to angiotensin II (inhibition of angiotensin converting enzyme (ACE)). 4. At equieffective ACE-inhibition doses in the anaesthetized, closed-chest dog, BW A575C (1.0 mg kg-1 by i.v. infusion) significantly reduces diastolic blood pressure, cardiac contractility and rate, whereas enalapril (1.0 mg kg-1 by i.v. infusion) only significantly reduces diastolic blood pressure. This blood pressure lowering effect of enalapril is not significantly different from that of BW A575C. In this preparation BW A575C and enalapril also significantly increase renal blood flow, and renal excretion of urine and Na+. There is however no significant difference between their renovascular effects. 5. These studies demonstrate that BW A575C produces changes in cardiac and renovascular function which can be ascribed to its being an ACE inhibitor and a beta-adrenoceptor blocking agent. The combination of these pharmacological properties results in a fall in blood pressure without compromising either cardiac performance or renal function. PMID- 2894875 TI - Suppressive effects of somatostatin in dog Purkinje fibres. AB - 1. The effects of somatostatin (SS, 1 nM-3 microM) on the electrical and mechanical activities of isolated Purkinje fibres of the dog were studied. 2. In most Purkinje fibres driven electrically in normal [K]o Tyrode solution, SS decreased the force of contraction slightly and had very little effect on the fast response action potential. However, in sensitive fibres SS induced a moderate reduction of action potential duration and contractile force in normal [K]o and depressed the slow response action potentials in high [K]o. 3. In spontaneously beating Purkinje fibres, SS decreased the regular rhythms slightly but abolished bursts of fast rhythms at a concentration as low as 1 nM. 4. When the fibres were depolarized in the presence of 0.2 mM barium or in Na-free solution, SS suppressed the Ca-dependent slow response action potentials. 5. These findings suggest that SS may suppress abnormal automatic activity of dog Purkinje fibres through a reduction of transmembrane Ca influx or a modulation of intracellular calcium. PMID- 2894876 TI - Relaxing actions of procaterol, a beta 2-adrenoceptor stimulant, on smooth muscle cells of the dog trachea. AB - 1. The effects of procaterol, a beta 2-adrenoceptor agonist, on smooth muscle cells of the dog trachea were investigated by use of microelectrode and isometric tension recording methods, and by measurement of Ca transients as estimated from the fura-2 fluorescence, adenosine 3':5'-cyclic monophosphate (cyclic AMP) and breakdown of phosphatidylinositols. 2. Procaterol hyperpolarized the membrane and increased the ionic conductance (above 10 nM) in a dose-dependent manner. These actions were inhibited by propranolol. 3. Procaterol inhibited the mechanical responses evoked by acetylcholine (ACh), histamine or 5-hydroxytryptamine (5-HT), in the presence or absence of Ca2+ in the bath solution, but not that evoked by high concentrations of ACh (1 microM). The ID50 value of procaterol for the peak amplitude of the ACh-induced contraction (30 nM) was 0.3 nM. The equivalent values for the histamine-induced phasic and tonic responses (10 microM) were 0.15 and 0.01 nM), respectively. 4. Procaterol (over 1 nM) increased the amount of cyclic AMP in a dose-dependent manner which was blocked by prior application of propranolol. 5. Procaterol did not alter the changes in the amounts of phosphatidylinositol 4,5-bisphosphate (PI-P2) and phosphatidic acid (PA) induced by ACh, histamine or 5-HT. Thus, the synthesis of inositol 1,4,5-trisphosphate is not affected by stimulation of the beta 2-adrenoceptor. 6. ACh increased the free Ca2+ concentration to a greater extent than that produced by histamine or 5-HT. These changes were reduced by procaterol, except for those induced by high concentrations of ACh (over 1 microM). 7. It is concluded that procaterol relaxes tissues precontracted by various agonists due to a reduction in the free Ca2+. This inhibitory action may be due to an increase in the amount of cyclic AMP but does not result from an inhibition of the hydrolysis of phosphatidyl inositols. The hyperpolarization induced by procaterol may partly contribute to the observed relaxation. PMID- 2894877 TI - Endothelium-derived relaxing factor and atriopeptin II elevate cyclic GMP levels in pig aortic endothelial cells. AB - 1. Two directly-acting stimulants of soluble guanylate cyclase, glyceryl trinitrate (0.1 microM) and sodium azide (10 microM), and a receptor-mediated stimulant of particulate guanylate cyclase, atriopeptin II (10 nM), each elevated the cyclic GMP content of primary cultures of pig aortic endothelial cells without affecting the cyclic AMP content. 2. Two receptor-mediated stimulants of adenylate cyclase, glucagon (1 microM) and isoprenaline (10 microM), had no effect on the cyclic AMP or cyclic GMP content of these cells, but the directly acting stimulant, forskolin (30 microM), induced a small increase in cyclic AMP content. 3. Three agents that release endothelium-derived relaxing factor (EDRF); bradykinin (0.1 microM), ATP (10 microM) and ionophore A23187 (0.1 microM), each markedly elevated the cyclic GMP content of pig aortic endothelial cells, but acetylcholine (1 microM) had no effect. None of these agents had any effect on cyclic AMP content. 4. Two agents that potentiate the actions of EDRF; M & B 22948 (100 microM) and superoxide dismutase (30 units ml-1), each elevated the cyclic GMP content of pig aortic endothelial cells without affecting the cyclic AMP content. Pretreating cells with catalase (100 units ml-1) did not affect the rise in cyclic GMP content induced by superoxide dismutase (30 units ml-1). 5. Pretreatment of pig aortic endothelial cells with haemoglobin (10 microM) reduced the resting content of cyclic GMP and blocked the increase in cyclic GMP content induced by glyceryl trinitrate (0.1 microM), sodium azide (10 microM), bradykinin (0.1 microM), ATP (10 microM), ionophore A23187 (0.1 microM), M & B 22948 (100 microM) and superoxide dismutase (30 units ml-1), but not that induced by atriopeptin II (10 nM). 6. Pretreatment of pig aortic endothelial cells with an inhibitor of soluble guanylate cyclase, methylene blue (20 microM), had no effect on the resting content of cyclic GMP. Methylene blue (20 microM) blocked the increase in cyclic GMP content induced by glyceryl trinitrate (0.1 microM), M & B22948 (100 microM) and bradykinin (0.1 microM), but not that induced by atriopeptin II (10 nM). 7. The data show that soluble guanylate cyclase, particulate guanylate cyclase and adenylate cyclase are present in pig aortic endothelial cells. They further suggest that EDRF, produced spontaneously or in response to vasoactive agents, elevates endothelial cyclic GMP content by stimulating soluble guanylate cyclase. It is possible that this may serve as a feedback loop by which the endothelial cell modulates EDRF production. PMID- 2894878 TI - Effect of chlorpromazine on sympathetic neuroeffector transmission in the rabbit isolated pulmonary artery and aorta. AB - 1. The effects of chlorpromazine on sympathetic neuroeffector transmission have been studied in the rabbit isolated pulmonary artery and aorta. 2. Chlorpromazine (10(-8)-10(-5) M), prazosin (10(-9)-10(-7) M) and phentolamine (3 x 10(-8)-3 x 10(-5) M) decreased the contractions of pulmonary artery evoked by electrical field stimulation (150 pulses; 3 Hz). The rank order of inhibitory potency (ID50) was prazosin greater than chlorpromazine greater than phentolamine. 3. Rauwolscine (3 x 10(-9) M-4 x 10(-6) M) enhanced the neurogenic response by up to 201%. However, higher concentrations (6 x 10(-6)-3 x 10(-5) M) reduced the contractions evoked by transmural stimulation. 4. The inhibitory effect of prazosin (10(-6) M) was reversible, while that of chlorpromazine (10(-8) M) was not. 5. Chlorpromazine (10(-8)-10(-4) M), desmethylimipramine (3 x 10(-9)-10(-5) M), cocaine (10(-7)-3 x 10(-4) M) and phentolamine (10(-5)-3 x 10(-4) M) reduced the accumulation of [3H]-noradrenaline ([3H]-NA, 10(-8) M) by aorta. The rank order of inhibitory potency (ID50) was: desmethylimipramine greater than chlorpromazine greater than cocaine greater than phentolamine. Prazosin (10(-7) 10(-5) M) and rauwolscine (10(-8)-10(-4) M) did not reduce [3H]-NA accumulation. 6. Chlorpromazine (10(-8)-10(-6) M) and prazosin (3 x 10(-9)-10(-7) M) antagonized the contractions of aorta evoked by exogenous noradrenaline (10(-9)-3 x 10(-4) M) and phenylephrine (10(-9)-3 x 10(-3) M). The pA2 values for chlorpromazine on the alpha 1-adrenoceptors were 8.24 (noradrenaline) and 8.27 (phenylephrine). The corresponding values for prazosin were 8.64 and 8.57, respectively. 7. It is concluded that chlorpromazine and prazosin are potent inhibitors of postsynaptic alpha 1-adrenoceptors. Chlorpromazine and phentolamine, unlike prazosin and rauwolscine, are also inhibitors of Uptake. PMID- 2894881 TI - Assent to ascent of the testis. AB - We report 13 boys in whom the testis ascended from the normal scrotal position to an undescended position. A patent processus vaginalis was identified in 10 patients at orchidopexy and is believed to have contributed to testicular ascent. The other three patients had retractile testes which were held in the high position by surrounding adhesions. PMID- 2894880 TI - Involvement of beta 2-adrenoceptor-mediated mechanisms in the cardiovascular responses to alpha 1- and alpha 2-adrenoceptor antagonism in conscious, unrestrained, Long Evans and Brattleboro rats. AB - 1. Intra-arterial blood pressures and heart rates were recorded in conscious, unrestrained, Long Evans and Brattleboro rats receiving sequential, continuous administrations of selective alpha 1- (prazosin) and alpha 2- (idazoxan) adrenoceptor antagonists. The same protocols were also run in the presence of ICI 118551 (a selective antagonist of beta 2-adrenoceptors). 2. Prazosin and idazoxan caused large, but transient, hypotensions in Long Evans and Brattleboro rats. In the continued presence of both drugs there were marked, intermittent, depressor episodes and tachycardias in both strains of rat. 3. In the presence of low or high doses of ICI 118551 the hypotensive responses to prazosin and idazoxan were markedly reduced in both strains of rat and blood pressures showed little variability, although intermittent tachycardias still occurred. 4. In adrenal demedullated Long Evans rats, the hypotensive responses to prazosin and idazoxan were attenuated and in the presence of both drugs, blood pressure was relatively steady, although intermittent tachycardias still occurred. 5. In the presence of prazosin and idazoxan, when a depressor episode was not occurring, administration of captopril caused hypotension in Long Evans and Brattleboro rats. In the latter, the reduction in blood pressure was sustained, whereas there was a recovery in blood pressure in Long Evans rats. This recovery was punctuated by depressor episodes, and was abolished by a V1-receptor antagonist (d(CH2)5DAVP). 6. Long Evans rats given two primed doses of the non-selective alpha-adrenoceptor antagonist, phentolamine, exhibited variation in blood pressure similar to that seen in the presence of prazosin and idazoxan. As in the latter case, blood pressure variability was inhibited by the beta 2-adrenoceptor antagonist, ICI 118551. 7. Administration of idazoxan into a lateral ventricle in Long Evans rats receiving phenoxybenzamine intravenously did not cause blood pressure instability. However, intravenous administration of idazoxan in the same animals produced intermittent depressor episodes and tachycardias similar to those seen in the presence of prazosin and idazoxan. 8. The simplest explanation of the results is that beta 2-adrenoceptor-mediated depressor mechanisms contribute to the hypotensive responses to alpha 1- and alpha 2-adrenoceptor antagonism. Furthermore, in the presence of adequate peripheral alpha 1- and alpha 2 adrenoceptor antagonism, blood pressure may be maintained by the renin angiotensin system and vasopressin (although it is only when the former system has been antagonized that a clear-cut pressor action of vasopressin is apparent). Under these conditions, blood pressure maintenance is interrupted by intermittent depressor episodes that are largely due to adrenal medullary activation. PMID- 2894882 TI - Total pancreatectomy in the MEN-1 syndrome. AB - A family with the multiple endocrine neoplasia Type 1 (MEN-1) syndrome, followed over three generations, is presented. In the first generation, one family member died after a history indicating Zollinger-Ellison syndrome. In the second generation endocrine pancreatic tumours were diagnosed or suspected in three out of five members. In the third generation, five out of seven members were investigated and four of these had positive tests at hormonal screening. Of particular diagnostic value in this family was the determination of peripheral serum levels of proinsulin and C-peptide, which were used as tumour markers both for diagnosis and in the postoperative follow-up. Two members in the third generation have been successfully managed by total pancreatectomy. A MEN-1 patient with malignant pancreatic tumours should be considered for total pancreatectomy if the pancreatic disease has caused high morbidity and mortality within the family. This is especially pertinent if the patient has multiple malignant tumours. PMID- 2894879 TI - Zolantidine (SK&F 95282) is a potent selective brain-penetrating histamine H2 receptor antagonist. AB - 1. The novel benzthiazole derivative zolantidine (SK&F 95282) is a potent antagonist of histamine at H2-receptors in guinea-pig atrium and rat uterus. Only apparent pA2 values of 7.46 and 7.26 respectively could be calculated since the slopes of the Schild plots were significantly less than unity. 2. Zolantidine is equally potent as an antagonist at histamine H2-receptors in guinea-pig brain. The compound inhibited histamine stimulated adenylate cyclase (pKi 7.3) and dimaprit stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation (approx pA2 7.63), and competed with [3H]-tiotidine binding (pKi 7.17). 3. Zolantidine is at least 30 fold more potent at H2-receptors than at other peripheral and central receptors investigated. 4. Infusion of zolantidine into rats produces a brain concentration greater than the plateau blood concentration (brain/blood ratio 1.45). 5. Zolantidine is thus characterized as a potent selective brain-penetrating H2-receptor antagonist, and will be a valuable pharmacological tool for investigating possible physiological and pathological roles for histamine in the central nervous system. PMID- 2894883 TI - Nifedipine and atenolol singly and combined for treatment of essential hypertension: comparative multicentre study in general practice in the United Kingdom. Nifedipine-Atenolol Study Review Committee. AB - A randomised double blind parallel group study was performed to compare the efficacy and acceptability of slow release nifedipine (maximum dose 40 mg twice a day) with those of atenolol (maximum dose 100 mg once a day) as single agents for the treatment of essential hypertension. Of 410 patients recruited almost exclusively from general practices in 22 centres in the United Kingdom 210 received nifedipine and 200 atenolol. Both drugs significantly reduced blood pressure, and control--a reduction of the diastolic pressure to less than 95 mm Hg--was obtained in about 65% of patients. Those who received nifedipine had more pronounced reductions in systolic pressure than those who received atenolol. One hundred and forty nine patients who failed to respond adequately to either atenolol or nifedipine in low doses were given both drugs once daily for eight weeks in a fixed combination capsule that contained atenolol 50 mg and nifedipine 20 mg. All patients showed further reductions in blood pressure, although those who were taking beta atenolol before the combination capsule had more pronounced reductions in systolic pressures. Twenty six patients (12%) were withdrawn because of adverse effects while taking nifedipine compared with 19 (10%) taking atenolol. Flushing and oedema were more common after the calcium antagonist, whereas diarrhoea and dyspepsia were more common after atenolol. The frequencies of headaches, dizziness, fatigue, and dyspnoea were equally distributed between the two groups. When the fixed combination capsule was taken side effects such as flushing and oedema continued. Nifedipine was more effective than atenolol in lowering systolic blood pressure, although neither drug used alone controlled the pressure of more than two thirds of the patients studied. When used in a fixed combination slightly better control of blood pressure was achieved with a lower dose of each drug. PMID- 2894884 TI - Health of long term benzodiazepine users. AB - The physical and psychological health of long term (over one year) users of benzodiazepines in one general practice was assessed by patients' self reporting of illness and by general practitioners' records. Of 3741 patients registered with the practice, 82 had been prescribed a benzodiazepine, and 64 of these agreed to enter the study. All but five of these patients were over 40 years of age, nearly a third (19) were given a diagnosis related to depression by interviewers, and between a third and a half reported a current physical illness. Long term treatment with benzodiazepines is not necessarily optimum management but may reflect the realities of general practice. PMID- 2894886 TI - Effect of high dose somatostatin analogue on growth hormone concentrations in acromegaly. PMID- 2894885 TI - Beta blockers, lipids, and coronary atherosclerosis: fact or fiction? PMID- 2894887 TI - [Retroviral infections by HIV-1, HIV-2 and AIDS-related complex in the Ivory Coast]. AB - The study of 500 blood donors, of 23 prostitutes, 22 confirmed AIDS cases and 19 ARC patients in Abidjan showed that HIV-2 prevalence in blood donors (3.4%) was somewhat higher than that of HIV-1 (2.4%). Furthermore HIV-2 alone was found associated with 14% of AIDS cases and 21% of ARC, while HIV-1 was associated with 32% of the cases. Antibodies to HIV-1 and HIV-2 were found in 54% of AIDS and ARC cases, as well as in 48% of the prostitutes sera. These preliminary results suggest that HIV-2 is pathogenic, being causally involved in some AIDS cases and does not protect from HIV-1 pathogenic potential. PMID- 2894888 TI - Gene mapping of X-linked choroideremia with restriction fragment-length polymorphisms [correction]. PMID- 2894890 TI - Comparison of monotherapy with enalapril and atenolol in mild to moderate hypertension. The Canadian Enalapril Study Group. AB - Therapy with 10 to 40 mg once daily of enalapril, a new angiotensin converting enzyme inhibitor, was compared with therapy with 50 to 100 mg once daily of atenolol in a double-blind randomized multicentre trial in 180 patients with a diastolic blood pressure (determined with the patient seated) of 95 to 115 mm Hg between March 1984 and April 1986. A total of 86 patients (61 men and 25 women with a mean age of 49.4 years and a mean blood pressure [and standard deviation] at entry into the trial of 155.5 [15.7]/101.0 [6.3] mm Hg) received enalapril, and 94 patients (63 men and 31 women with a mean age of 50.9 years and a mean blood pressure at entry of 156.6 [16.6]/101.2 [5.7] mm Hg) received atenolol. After a placebo run-in period the patients received increasing dosages of medication every 2 weeks until the target diastolic blood pressure of 90 mm Hg or less was achieved on two consecutive visits, the maximum dosage was reached, or the patient withdrew because of adverse effects. At 14 weeks the mean blood pressure was 141.6 (18.0)/90.1 (9.5) mm Hg in the enalapril group (61 patients) and 140.0 (17.1)/88.4 (8.7) mm Hg in the atenolol group (54 patients). The target diastolic blood pressure was achieved on completion of therapy (between weeks 10 and 14) in 67 (77%) of the patients receiving enalapril and 75 (79%) of the patients receiving atenolol. Compliance was similar in the two groups. Seven patients withdrew because of adverse effects, three in the enalapril group and four in the atenolol group. The results suggest that once-daily monotherapy with enalapril, 10 to 40 mg, is effective in the treatment of mild to moderate hypertension and is as effective as and tolerated as well as once-daily therapy with atenolol, 50 to 100 mg. PMID- 2894889 TI - Medical treatment of inflammatory bowel disease: new therapies, new drugs. AB - Ulcerative colitis, ulcerative proctitis and Crohn's disease are chronic inflammatory conditions that affect the gastrointestinal tract. Conventional treatment has stressed the role of anti-inflammatory agents to suppress the inflammatory response. New compounds that can deliver 5-aminosalicylic acid to the colon have recently been released in Canada. Metronidazole and azathioprine may also be of benefit in Crohn's disease. Therapy with cyclosporine and clonidine should be based on the results of further clinical trials. The use of nutritional support as primary therapy in Crohn's disease appears promising. At present, both pharmacologic and nutritional therapies should be considered in the treatment of inflammatory bowel disease. PMID- 2894891 TI - Multiplicity of transforming growth factors in human malignant effusions. AB - Human malignant effusions were found to contain transforming growth factor (TGF) activity capable of stimulating anchorage independent growth of nontransformed rodent fibroblasts. Bio-Gel P-60 chromatography of acid-ethanol extracts demonstrated the presence of three populations of TGF activities in 57% of malignant effusions. Two activities were similar to those of TGF alpha and TGF beta as judged by their size (Mr approximately equal to 6,000 and approximately equal to 25,000, respectively), biological activity (ability to stimulate anchorage independent growth of NRK fibroblasts in the absence or presence of epidermal growth factor, respectively), and capacity to competitively inhibit binding of 125I-labeled epidermal growth factor to A-431 membranes and 125I-TGF beta to baby hamster kidney fibroblasts, respectively. In addition a third factor which stimulated anchorage independent growth of nontransformed rodent fibroblast and human colonic epithelial cells was also recovered following Bio-Gel P-60 chromatography of extracts from several cytology positive human malignant effusions of patients with colonic and breast carcinoma as well as other malignancies. The latter malignant effusion related transforming growth factor was not present in benign or cytology negative effusions. Malignant effusion related TGF factor was inactivated by sulfhydryl reducing agents, heat, and trypsin treatment but was stable in 1% acetic acid and ethanol. Partial purification was accomplished by chromatography of an acid-ethanol extract on Bio Gel P-60 followed by high performance liquid chromatography with C18-mu Bondapak to yield a nearly pure protein with apparent molecular weights of 64,000 by sodium dodecyl sulfate-polacrylamide gel electrophoresis when run in nonreducing conditions and 32,000 when run in reducing conditions. Malignant effusion related TGF was able to stimulate anchorage independent growth of nontransformed fibroblasts in the absence of other growth factors. It did not competitively inhibit binding of 125I-labeled epidermal growth factor, 125I-TGF beta, or 125I labeled platelet derived growth factor. Therefore, this factor isolated from human malignant effusions may be distinct from previously described transforming growth factors. Collectively these observations indicate that human malignant effusions contain a multiplicity of transforming growth factors. It is possible that the malignant effusion related transforming growth factors play a role or reflect the metastatic growth properties of various tumors. PMID- 2894892 TI - Enhancement of adriamycin antitumor activity by its binding with an intracellular sustained-release form, polymethacrylate nanospheres, in U-937 cells. AB - We investigated the antitumor activity of Adriamycin on a monocytic-like cancer cell line U-937 after its binding on polymethacrylate nanospheres (diameter, 270 350 nm). Compared to free Adramycin (F-ADR), nanosphere-bound Adriamycin (B-ADR) exhibits a 3-fold enhancement of cytotoxicity, as determined by cell growth inhibition and DNA synthesis, after continuous exposure to 0.02 and 0.04 microgram/ml. The 90% growth inhibition concentration was 0.051 microgram/ml for F-ADR and was 0.018 microgram/ml for B-ADR (P less than 0.001). Furthermore, the nanosphere densities per cell play an important role since for the same drug concentration the higher the density increases, the better the activity is. Indeed, after 4 days of incubation in a medium containing 160 nanospheres at 0.5 fg/cell, the cell counts were 62.8 +/- 12.8% (SD) of the initial inoculum and they were only 16.1 +/- 0.1% after incubation in a medium containing 800 nanospheres at 0.1 fg/cell (P less than 0.001). A comparable enhancement of activity regarding the nanosphere densities was observed after a 24-h exposure to 0.02 and 0.05 microgram/ml. Short-term uptake studies showed that B-ADR accumulation was higher with B-ADR than with F-ADR. In addition, the efflux kinetics was modified. For cells exposed to F-ADR for 4 h, the efflux half-life was 23.7 +/- 7.7 h and the area to infinity under the efflux curve was 8.6 +/- 2.8 micrograms/mg protein x h-1. For cells exposed to B-ADR, the efflux half-life increased to 85.9 +/- 19.2 h and the area to infinity under the efflux curve to 29.6 +/- 6.6 micrograms/mg protein x h-1 (P less than 0.001). Electron transmission microscopy and previous findings have revealed that B-ADR was well internalized into cells. Our data support the hypothesis that B-ADR acts as an intracellular drug release complex after endocytosis. The findings regarding the number of nanospheres per cell and dose-effect relationships are consistent with mechanisms of drug actions extending to membrane domains. PMID- 2894894 TI - Tissue distribution of P-glycoprotein encoded by a multidrug-resistant gene as revealed by a monoclonal antibody, MRK 16. AB - A monoclonal antibody, MRK 16, specific to a human myelogenous leukemia cell line, K-562, and resistant to Adriamycin, was used to determine the localization of the antigen molecules (P-glycoprotein) recognized by the monoclonal antibody. P-glycoprotein was found to be expressed very strongly in the adrenal cortex and medulla of adults and strongly in the renal tubules of the kidney and the placenta. Interestingly, P-glycoprotein was not distributed in fetal and neonatal adrenals, and thus may be closely related to adrenal maturation. A high level of P-glycoprotein expression was also seen in one case each of untreated lung cancer (one of ten) and breast cancer (one of nine). Immunoelectron microscopically, the P-glycoprotein was distributed evenly on the membranes of K-562/ADM and 2780 cells. These results imply that the presence of the glycoprotein may be useful as a marker for in vitro studies of multidrug resistance in various malignancies and as an indicator of therapeutic efficacy of ex vivo eradication of multidrug resistant cancer cells, although other mechanisms of drug resistance may exist, and there is a possibility that this MRK 16 monoclonal antibody may not recognize all P-glycoprotein. PMID- 2894893 TI - Cytogenetic and phenotypic analysis of a human colon carcinoma cell line resistant to mitoxantrone. AB - A human colon carcinoma cell line selected for a 21-fold resistance to mitoxantrone was cross-resistant to the anthracycline, doxorubicin, but not to the anthracene, bisantrene. A 2-fold resistance was observed with vinblastine, another drug associated with multidrug resistance. Net intracellular mitoxantrone and doxorubicin accumulation were decreased at 1 h for all dose levels in the resistant cell line compared to the sensitive cell line. Although the resistant cells were more resistant to mitoxantrone than doxorubicin, the net accumulation of mitoxantrone was only 19% less than the sensitive cell line; whereas doxorubicin accumulation was decreased by 49%. No significant difference between the sensitive and resistant cell lines was observed in the initial accumulation of mitoxantrone; however, the efflux of mitoxantrone was increased in the resistant cell line. Verapamil did not overcome the resistance to mitoxantrone and did not increase the net accumulation of drug. No alterations in the electrophoretic mobility of membrane proteins were observed. Using immunoblotting techniques, the resistant cell line did not express P-glycoprotein which is frequently observed for cells resistant to anthracycline antibiotics. Cytogenetic analysis showed a putative homogenously staining region on the short arm of chromosome 7 in the resistant cell line. The limited cross-resistant phenotype, lack of verapamil reversal, nondetection of P-glycoprotein, and cytogenetic evidence of gene amplification suggests the involvement of a novel drug-resistant gene associated with resistance to mitoxantrone. PMID- 2894895 TI - Management of catatonic stupor with L-dopa. PMID- 2894896 TI - [Prenatal diagnosis of hemophilia A in the 2d trimester and its problems]. PMID- 2894897 TI - [A study on the relationship between gamasid mites and epidemic hemorrhagic fever]. PMID- 2894898 TI - [Experimental study on bitting, trans-stadial and transovarian transmission of epidemic haemorrhagic fever virus by gamasid mites Ornithonyssus bacoti]. PMID- 2894899 TI - Novel agents affecting enkephalinergic and histaminergic transmissions in brain. PMID- 2894901 TI - Tobacco chloroplast gene coding for subunit I of proton-translocating ATPase: comparison with the wheat subunit I and E. coli subunit b. AB - The tobacco chloroplast gene for subunit I of proton-translocating ATPase is located 405 bp down-stream from the gene for subunit III and 58 bp upstream from the gene for subunit alpha in the same DNA strand. This gene is interrupted by a 695 bp intron. The coding region contains 552 bp (184 codons) and its deduced amino acid sequence shows 78% homology with that of the wheat gene for subunit I. PMID- 2894900 TI - Coordinated leading and lagging strand synthesis during SV40 DNA replication in vitro requires PCNA. AB - Proliferating cell nuclear antigen (PCNA) is a cell cycle and growth regulated protein required for replication of SV40 DNA in vitro. Its function was investigated by comparison of the replication products synthesized in its presence or absence. In the completely reconstituted replication system that contains PCNA, DNA synthesis initiates at the origin and proceeds bidirectionally on both leading and lagging strands around the template DNA to yield duplex, circular daughter molecules. In contrast, in the absence of PCNA, early replicative intermediates containing short nascent strands accumulate. Replication forks continue bidirectionally from the origin, but surprisingly, only lagging strand products are synthesized. Thus two stages of DNA synthesis have been defined, with the second stage requiring PCNA for coordinated leading and lagging strand synthesis at the replication fork. We suggest that during eukaryotic chromosome replication there is a switch to a PCNA-dependent elongation stage that requires two distinct DNA polymerases. PMID- 2894902 TI - A comparative evaluation of intubating doses of atracurium, d-tubocurarine, pancuronium and vecuronium in children. AB - To determine the onset and recovery times and haemodynamic effects of intubating doses of atracurium (0.4 mg.kg-1), d-tubocurarine (0.8 mg.kg-1), pancuronium (0.12 mg.kg-1), and vecuronium (0.07 mg.kg-1), sixty-seven children aged one to eight years were studied under halothane and nitrous oxide anaesthesia. The time to maximum twitch depression and the time to recovery to T1/Tc 25 per cent were recorded with an integrated evoked EMG recorder. The heart rate and systolic blood pressure were recorded for five minutes after drug administration and prior to intubation. There was no difference in onset times between drugs. The recovery time to T1/Tc 25 per cent following vecuronium (25.5 +/- 6.3 min) was shorter than following atracurium (37.5 +/- 7.0 min). Recovery times for d-tubocurarine and pancuronium were greater than sixty minutes. Elevation of heart rate occurred after administration of pancuronium (+29.8 per cent to +38.6 per cent) and d tubocurarine (+31 per cent to +34.9 per cent), but no change was observed after atracurium or vecuronium. Elevation of blood pressure was greatest following pancuronium (+10.8 to +14.8 per cent). No significant change was observed following atracurium or vecuronium. A transient lowering of blood pressure (-9.3 per cent) occurred following d-tubocurarine. PMID- 2894903 TI - Priming with nondepolarizing relaxants for rapid tracheal intubation: a double blind evaluation. AB - Results of a series of controlled, randomized, double-blind trials investigating intubation conditions with priming sequences of nondepolarizing relaxants are reported. In Phase I of the study the groups received: Group A, tubocurarine (DTC) 3 mg + succinylcholine 1.5 mg.kg-1, Group B, atracurium 0.05 mg.kg-1 + 0.35 mg.kg-1, Group C, vecuronium, 0.01 mg.kg-1 + 0.07 mg.kg-1; in Phase II: Group D, no relaxant, Group E, DTC 0.05 mg.kg-1 + vecuronium 0.07 mg.kg-1, Group F, vecuronium 0.01 mg.kg-1 + vecuronium 0.12 mg.kg-1; in Phase III, Group G, DTC 3 mg + succinylcholine 1.5 mg.kg-1, Group H, vecuronium 0.01 mg.kg-1 + 0.09 mg.kg 1, Group I vecuronium 0.1 mg.kg-1 as a single bolus. Intubation conditions were assessed at 60 seconds. A seven-minute priming interval was used in Phase I and II and a four-minute interval was used in Phase III. Priming produced significantly better intubating conditions than an equivalent single bolus; however, intubating conditions with priming did not appear to match the uniformly excellent conditions produced by succinylcholine. The data suggest that a four minute priming interval is as effective as a seven-minute interval. The results of this study differed substantially from previous unblinded studies; therefore, it is suggested that a randomized, double-blind design with simultaneous succinylcholine controls be considered a prerequisite for future studies of intubation conditions. PMID- 2894904 TI - Effect of terfenadine and placebo on symptoms after nasal allergen provocation. AB - Terfenadine (60 mg b.i.d.) was compared with placebo in a randomized, double blind, cross-over study in twenty-three patients with birch pollen allergy. The patients were treated during two 7-day periods separated by a 2-week wash-out period during a season free from birch pollen. Nasal provocations with birch pollen extracts were made at study entry and after each treatment period. Blockage (rhinomanometry), secretion (weight) and sneezings (number) were compared between treatments. The results showed a significant inhibitory effect of terfenadine on secretion and sneezing, but no significant difference between treatments with regard to blockage. Terfenadine showed no signs of sedative properties or inhibition of salivation. PMID- 2894905 TI - Changes in serum enzymes in moderate drinkers after an alcohol challenge. AB - When 14 "moderate" drinkers abstained from alcohol for four weeks, the activity of gamma-glutamyltransferase (GGT; EC 2.3.2.2) in their serum showed a large decrease. Immediately after the period of abstention, an orally given ethanol challenge of 1 g/kg produced a marked increase in serum GGT at 24 h, followed by a slow decline thereafter. Aspartate amino-transferase activity in serum was significantly increased at 24 h; however, alkaline phosphate, alanine aminotransferase, and lactate dehydrogenase showed much smaller or no changes. An abnormal increase in lactate dehydrogenase isoenzyme 5 was observed in seven subjects. In some of the moderate drinkers, liver biopsies showed mild chronic hepatitis or nonspecific changes. Eight nondrinking controls showed only slight increases in serum GGT following the same alcohol challenge; results for the other enzyme tests were unchanged. We consider it probable that pre-existing liver disease affects the response to ethanol, so that greater amounts of GGT are released from hepatic tissue; alternatively, drinkers may have a higher GGT activity in this tissue as a result of enzyme induction by ethanol. The alcohol challenge test was an effective discriminator between moderate drinkers and abstainers. PMID- 2894906 TI - Urinary enzymes and low-molecular-mass proteins as indicators of diabetic nephropathy. AB - We measured the excretion rates of six urinary enzymes that either originate from the proximal renal tubule, like alanine aminopeptidase (EC 3.4.11.2), alkaline phosphatase (EC 3.1.3.1), gamma-glutamyltransferase (EC 2.3.2.2), and N-acetyl beta-D-glucosaminidase (EC 3.2.1.30), or that are typical low-molecular-mass proteins, like lysozyme (EC 3.2.1.17) and pancreatic ribonuclease (EC 3.1.27.5). These rates were compared with those of total protein and albumin in urine of 36 insulin-dependent diabetic men and 30 healthy men. Seventeen of the diabetics had "clinical proteinuria," defined as excretion of more than 7.5 g of protein per mole of urinary creatinine (group B). Group A comprised the 19 diabetics without proteinuria. Except for gamma-glutamyltransferase, the excretions of enzymes and proteins were significantly higher in diabetics than in controls and were greater in group B than in group A. N-Acetyl-beta-D-glucosaminidase was the analyte most often increased in group A (89%), followed by albumin and alkaline phosphatase (each 32%). All patients in group B showed increased excretion of N-acetyl-beta-D glucosaminidase. We conclude from the comparative data that this enzyme may be useful as an early predictor of diabetic nephropathy. PMID- 2894907 TI - HLA and adult T cell leukaemia: HLA-linked genes controlling susceptibility to human T cell leukaemia virus type I. AB - HLA antigens of patients with adult T cell leukaemia (ATL), T cell malignant lymphoma (T-ML), and healthy carriers of human T cell leukaemia virus type I (HTLV-I) were investigated in an endemic area of ATL in Japan. Sixty-two patients with ATL were subdivided into three groups based on their clinical features, including two unclassified patients; 36 acute type, 10 chronic type, and 14 smouldering type. The frequency of HLA-Bw62 was significantly increased in acute ATL, compared with control (Pc less than 0.0002). Increased frequency of HLA-DQw3 was observed in patients with ATL, T-ML positive for the antibody to HTLV-I (Ab positive), and Ab-positive healthy carriers, compared with control (Pc less than 0.001, Pc less than 0.01 and Pc less than 0.0001, respectively). In addition, class I HLA antigens of peripheral lymphocytes of patients with ATL, especially acute ATL, showed altered expression, either extra antigens or decreased antigens. Analysis of 21 families, where more than two members were Ab-positive, showed that there was no linkage between the HLA complex and susceptibility to the virus infection. In 44 couples, in which either or both spouses were Ab positive, no association with class I HLA antigens was found in either Ab positive spouses or Ab-negative spouses. These findings might indicate that one class II HLA-linked gene controlled susceptibility to HTLV-I infection, and another class I HLA-linked gene exerted an influence on the clinical course of ATL. PMID- 2894909 TI - Chronotoxicity of beta-adrenoceptor blocking agent in spontaneously hypertensive rats. AB - 1. Chronotoxicity of a single LD50 dosage of beta-adrenoceptor blocking agent, pindolol, was determined in spontaneously hypertensive rats (SHR) and Wistar Kyoto control rats (WKY). 2. The 24 h mortality was greater when pindolol was administered at 00.00 h than when it was administered at 12.00 h in both SHR and WKY. 3. The chronogram of the mortality in SHR was similar to that in WKY. 4. These results indicate that the mode of circadian variation in the acute toxicity of pindolol in SHR is not different from that in WKY. PMID- 2894908 TI - Rapid diagnosis of rabies and post-vaccinal encephalitides. AB - In an attempt to establish the diagnoses of rabies post-vaccinal encephalitis (PVE) and early rabies encephalitis, paired serum and CSF levels of rabies neutralizing antibody (Rab) and rabies specific-IgM (RIgM) were compared in 12 PVE, 10 rabies and five control patients with similar presenting clinical features. Rapid methods of rabies antigen detection were evaluated in 17 patients. All 12 PVE patients had Rab in their serum and in eight it was also present in the CSF. These same eight had RIgM in the serum, and in seven also in the CSF. The CSF antibodies may have originated in the plasma since six patients had a high albumin quotient indicating leakage across the blood-brain barrier. Among the rabies patients, only the two vaccinated ones had serum Rab; this was also detected in the CSF of one and RIgM was in the CSF of the other. A raised IgG Index, indicating intrathecal synthesis of IgG was seen in five of 12 PVE patients. This did not correlate with the presence of CSF rabies antibody, suggesting production of antibody to other vaccine antigens of neural origin. The diagnosis of rabies encephalitis in life was made by antigen detection in a skin biopsy. No false positive results occurred and the method was as efficient as immunofluorescence of a post-mortem brain biopsy. PMID- 2894910 TI - Characterization and localization of (-)[125I]-cyanopindolol binding to non-beta adrenoceptor sites in dog kidney. AB - 1. (-)[125I]-Cyanopindolol (CYP) binding to non-beta-adrenoceptor sites in dog kidney was characterized in homogenate preparations and their distribution in sections determined using autoradiography. 2. In homogenate studies, (-)[125I] CYP bound to a single population of non-interacting sites (Bmax = 5.45, s.e.m. = 1.00 fmol/mg wet weight; nH = 0.99, s.e.m. = 0.01) with high affinity (KD = 3.84, s.e.m. = 0.76 nmol/l, n = 40. 3. In competition studies, compounds selective for alpha- and beta-adrenoceptors, muscarinic cholinoceptors and receptors for 5-HT, histamine and benzodiazepines, calcium channel antagonists, catecholamine uptake inhibitors, MAO inhibitors and adrenergic neurone blockers were ineffective at concentrations of 10 mumol/l. 4. Compounds selective for dopamine D1-receptors (fluphenazine, SCH 23390 and SK & F 82526) and D2-receptors (pimozide, domperidone, spiperone, haloperidol, sulpiride, cis- and trans-flupenthixol) competed with similar affinities (5-25 mumol/l) for (-)[125I]-CYP binding. 5. In autoradiographic studies, (-)[125I]-CYP binding to non-beta-adrenoceptor sites was localized over glomeruli, juxtaglomerular apparatus, distal tubules, blood vessels and medullary rays and tubules. 6. It is concluded that in dog kidney, ( )[125I]-CYP binds to a site closely associated with dopamine receptors. PMID- 2894911 TI - Three-week beta-adrenergic blockade does not impair or improve general intellectual function in young healthy males. AB - The widespread use of beta blockers in treatment of both cardiovascular and nonvascular conditions has generated interest in changes in functions of the central nervous system during treatment. We studied the effect of 3 weeks of beta blockade on learning and memory ability, concentration, and verbal abstraction in 32 young normotensive healthy men. We chose healthy males to exclude the possible influence of changes related to a hypertensive state. Subjects were randomized into a 3-week treatment protocol with either atenolol 50 mg X 2 (cardioselective, hydrophilic), metoprolol 100 mg X 2 (cardioselective, lipophilic), propranolol 80 mg X 2 (noncardioselective, lipophilic), or placebo X 2. Each subject underwent two neuropsychological testing sessions. We found no significant enhancement or impairment of intellectual or psychomotor performances after the 3-week treatment with beta-adrenergic-blocking agents compared to a placebo-treated control group. Differences in pharmacokinetic profiles of the drugs (e.g., central nervous system penetrability, lipophilicity, or membrane-stabilizing effect) did not influence the test outcome. Antihypertensive treatment with beta blockers over a prolonged period does not affect young peoples' learning and memory abilities or reasoning powers, nor their ability to concentrate and perform psychometric tasks. PMID- 2894912 TI - Hematogenously acquired infection of a total knee arthroplasty by Clostridium perfringens. AB - A 64-year-old man with total knee arthroplasty for tricompartmental osteoarthritis had a postoperative course complicated by an attack of acute cholecystitis and was treated with cholecystectomy. The TKA was hematogenously seeded with Clostridium perfringens, which necessitated emergency removal of the implants, debridement, and ultimately arthrodesis. PMID- 2894913 TI - Sulphasalazine in arthritis--an old drug rediscovered. AB - Sulphasalazine (salicyl-azo-sulphapyridine) has been in clinical use for over 40 years. Although the drug was originally introduced for the treatment of 'rheumatic polyarthritis' and ulcerative colitis, it is only in the past 10 years that its value in rheumatology has been appreciated. Controlled studies indicate that the drug is an effective remittive agent in both rheumatoid arthritis and ankylosing spondylitis. This is an area of great research interest since the drug is proving to be a useful tool for investigating the aeteology and pathogenesis of these diseases. PMID- 2894914 TI - A role for computers in diabetes care? PMID- 2894915 TI - In vitro mitogenesis of peripheral blood lymphocytes from rainbow trout (Salmo gairdneri). AB - 1. In vitro mitogenesis of rainbow trout peripheral blood lymphocytes (RBT PBL) was investigated to assess the applicability of this procedure in assessment of fish health. The assay variables of media, mitogen type and concentration, serum supplementation, lymphocyte isolation procedure, and duration of incubation were assessed. 2. Concanavalin A (Con A) stimulated greater proliferation of RBT PBL than did lipopolysaccharide (LPS), phytohemagglutinin (PHA), or pokeweed mitogen (PWM). 3. RBT PBL, cultured with 10 micrograms Con A/ml and incubated for four or five days, exhibited greater proliferation than with other treatment combinations. 4. The degree of Con A-induced PBL proliferation varied significantly (P less than 0.05) among fish. The mean was positively correlated with the relative standard deviation and thus exhibited significant heteroscedasticity. 5. Human serum, as an alternative to FBS supplementation of the culture medium, did not enhance RBT PBL proliferation or reduce variation in mean proliferation. 6. Power analysis with variance estimates from this study reveal that sample size requirements of further studies under the given conditions could severely limit the applicability of this procedure for RBT health assessment. Further work in this area should center around standardization of culture conditions pertaining to the source of protein supplementation. PMID- 2894916 TI - Repetitive excitation of bursts of action potentials in the rat hippocampus following single shock stimulation. AB - 1. Post-stimulus time (PST) histograms of rat hippocampal cells were recorded in vivo following single-shock stimulation of the fornix. 2. The PST histograms displayed a series of peaks of decreasing amplitude, similar to damped oscillatory responses previously recorded in cats and rabbits. 3. The effect of increased background activity was investigated by recording histograms with concurrent pulse train stimulation of the contralateral hippocampus. The histograms showed a decreased latency to the onset of the second peak. 4. Damped oscillatory activity seen in the in vivo rat preparation could not be elicited in the in vitro rat slice preparation. Thus species differences cannot account for the absence in slice studies of this type of damped oscillatory activity. 5. We conclude that the level of spontaneous activity is one factor contributing to the genesis of multiple peaks in histograms in the in vivo preparation. PMID- 2894917 TI - Enzymatic inhibition of lysine transport across the small intestine in vivo. AB - 1. Trypsin, at different concentrations, significantly inhibited lysine absorption (P less than 0.05) in a dose-dependent pattern. 2. Maximum inhibition equivalent to 35% below control value was reached with 10 micrograms/ml (100 BAEE units) trypsin with a non-reversible inhibitory effect. 3. Chymotrypsin at 10 micrograms/ml produced a significant decrease (P less than 0.05) of lysine absorption although it did not exceed 5%. Perfusion of both enzymes did not show an additive inhibitory effect. 4. Lysine absorption showed a 39% decrease with 10 micrograms/ml trypsin and 1 X 10(-4) M ouabain, whereas ouabain alone produced 34% inhibition. 5. Lysine absorption showed a 71% decrease with 10 micrograms/ml trypsin in a sodium-free medium, and 70% inhibition with Na-free medium alone. 6. The inhibition of lysine absorption after trypsin treatment could be due to inhibition of the active component of lysine transport. PMID- 2894918 TI - Evidence of loss of a suggested genetic polymorphism in the blood potassium contents of zoo-living Barbary sheep Ammotragus lervia (Pallas 1777). AB - 1. Concentrations of potassium and iron were measured in blood samples of 15 zoo living Barbary sheep by atomic absorption spectrophotometry. 2. In analogy with the situation in Ovis it is suggested that a blood potassium polymorphism is also found in Ammotragus. 3. However, in the Frankfurt line at least, one of the presumed alleles is likely to be lost due to inbreeding. PMID- 2894919 TI - Report on the Second Canadian Workshop on Platelet Serology. PMID- 2894921 TI - The safety of combined thrombolysis and beta-adrenergic blockade in patients with acute myocardial infarction. A randomized study. AB - To assess the safety of combined intervention in acute myocardial infarction, a pilot study of thrombolysis and beta-adrenergic blockade was performed. Twenty five subjects were randomized to therapy with intravenous (IV) metoprolol and IV streptokinase (group 1) or to IV metoprolol (group 2) alone. Two-dimensional echocardiography was performed before intervention and five days later. The mean time from onset of symptoms to intervention was 1.92 hours. No major adverse reactions related to the intervention were observed in either group. Significant improvement from baseline was observed with combined therapy on both the biplane mean ejection fraction (p less than .02) and a calculated wall motion index of regional wall motion abnormalities (p less than .002). The presumed reperfusion rate was significantly higher in group 1 (p less than .03). Intravenous metoprolol and IV streptokinase in combination was found to be safe in the acute phase of acute myocardial infarction when administered to appropriate patients without contra-indications and deserves further study. PMID- 2894922 TI - The role of new antihypertensive drugs. PMID- 2894920 TI - Esmolol: safety and efficacy in postoperative cardiothoracic patients with supraventricular tachyarrhythmias. AB - Esmolol, an intravenous, ultrashort-acting beta-blocker, was studied for its ability to safely control supraventricular arrhythmias up to 24 hours in 15 postoperative cardiothoracic surgery patients with atrial fibrillation or flutter and rapid ventricular response. Esmolol obtained an initial therapeutic response in nine (60 percent) patients. Mean heart rate for the 15 patients was reduced from 139 +/- 12 beats/min before therapy to 106 +/- 21 beats/min during esmolol infusion (p less than 0.01). The mean time to a therapeutic response after initiation of therapy, using a multistep titration regimen (500 micrograms/kg/min loading infusions over one minute, prior to incremental titration steps from 50 to 300 micrograms/kg/min over 4 to 14 minutes), was 22 +/- 9 minutes, and therapy was continued for 17 +/- 9 hours in responders. Esmolol significantly lowered blood pressure in the group studied and resulted in mild supine or orthostatic hypotension in ten (67 percent) patients. Side effects, including hypotension (10/15 patients), gastrointestinal disturbances (2/15), and weakness or somnolence (6/15), were transient and were not associated with serious clinical sequelae. We conclude that esmolol is effective for rate control in a majority of postoperative cardiothoracic surgery patients with atrial fibrillation or flutter. Side effects, although mild, occur relatively frequently, limiting prolonged infusions and warranting close surveillance of patients. PMID- 2894923 TI - Bordetellae and charcoal horse blood agar: inactivation of antibiotics in agar during prolonged incubation for susceptibility testing. AB - We examined the degree of inactivation of 22 antibiotics caused by prolonged incubation at 36 degrees C of agar plates during agar dilution susceptibility testing of Bordetellae. Fresh antibiotic-containing plates of charcoal horse blood agar and plates which had been held at 36 degrees C for 2 or 3 days prior to inoculation were inoculated with strains of Bordetella pertussis and Bordetella parapertussis and incubated for 2 days. Then the MICs were compared. Most antibiotics showed a loss of activity of up to four dilution steps after prolonged incubation. Further studies with other slow-growing organisms and other complex media are needed. PMID- 2894924 TI - Antral D and G cell distribution in gastric and duodenal ulcer. PMID- 2894925 TI - Intrauterine infection of epidemic hemorrhagic fever (EHF) via placenta. PMID- 2894926 TI - GATA tandem repeats detect minisatellite regions in blowfly DNA (Diptera: Calliphoridae). AB - A DNA probe containing GATA tandem repeats detected numerous dispersed minisatellite regions in the genomes of the blowflies Chrysomya rufifacies and Calliphora erythrocephala. These regions seemed to be actively transcribed into poly(A)+ RNA in a tissue-specific manner. When genomic DNA of blastoderm embryos was compared with adult genomic DNA some loci hybridizing to GATA displayed a marked stage-specific variation in length. In Calliphora, a small sex-linked dimorphism of GATA mini-satellite-associated restriction fragments was observed. PMID- 2894928 TI - The molecular genetics of diabetes mellitus. AB - Diabetes mellitus is a clinically heterogeneous disorder which is characterized by hyperglycaemia due to an absolute or relative deficiency of insulin. Both genetic and non-genetic factors contribute to its development and, as such, it represents a multifactorial disorder. In addition, it may also be, in some instances, a polygenic disorder resulting from the cumulative effects of several genes with or without environmental factors. Serological and/or DNA markers for genes that confer susceptibility to the insulin-dependent form of the disorder (IDDM; type 1) have been identified in the HLA-D region of chromosome 6 and near the insulin gene on chromosome 11. Patients with non-insulin-dependent diabetes mellitus (NIDDM; type 2) make up a more heterogeneous group than those with IDDM and it is likely that in these patients similar clinical phenotypes may be produced by different genetic defects. The synthesis of either an abnormal insulin/proinsulin molecule or an abnormal insulin receptor can confer susceptibility to NIDDM. The genes encoding insulin and the insulin receptor are on chromosomes 11 and 19, respectively. In addition, studies of restriction fragment length polymorphism and disease associations suggest that two other genes may contribute to the development of NIDDM on chromosome 11, one near the insulin gene on the short arm of this chromosome and the other near the apolipoprotein A-I gene on the long arm. None of the susceptibility genes that have been identified to date causes diabetes in the absence of other genetic or non-genetic contributing factors, which is consistent with a multifactorial or polygenic origin for this disorder. PMID- 2894927 TI - Use of DNA polymorphisms of the apolipoprotein genes to study the role of genetic variation in the determination of serum lipid levels. AB - Cloned DNA probes for the apolipoprotein B (apoB) gene and the gene cluster for apoA-I/C-III/A-IV were used to detect restriction fragment length polymorphisms (RFLPs) at these two loci. Samples have been obtained from clinically well individuals, and the RFLP genotypes of each individual have been determined. The data show that at the locus for apoB, genetic variation associated with an RFLP detected by the enzyme XbaI (but not that associated with RFLPs detected by MspI or EcoRI) is involved in determining the normal levels of serum total cholesterol and low density lipoprotein (LDL) cholesterol. In our study, genetic variation associated with the XbaI RFLP accounts for 14% of the total phenotypic variance in cholesterol levels. Information from all three RFLPs can be used in conjunction to give a better definition of the underlying genetic variation. Data from a second study show that genetic variation in the apoA-I/C-III/A-IV gene cluster, associated with the PstI RFLP, is involved in determining the level of apoA-I and, to a lesser extent, the levels of high density lipoprotein (HDL). When genotypes from three RFLPs were used in conjunction as a haplotype, genetic variation in this gene cluster was shown to account for 16% of the phenotypic variance in apoA-I concentration and for 8% of the phenotypic variance in HDL concentration in our sample. These associations suggest that the isolation and sequencing of the apoB and the apoA-I/C-III/A-IV genes from different individuals will give useful information about how changes in the DNA sequence of these genes may lead to alterations in the levels of their respective apolipoproteins, in the level of the lipoproteins with which they are associated and, possibly, in the levels of lipids in the serum. PMID- 2894930 TI - The molecular genetics of HLA-related disorders. AB - The HLA region on the short arm of chromosome 6 contains a set of highly polymorphic loci responsible for regulating the immune response. Particular haplotypes, defined serologically, have been associated with a risk of developing certain autoimmune diseases such as insulin-dependent (juvenile-onset) diabetes mellitus, multiple sclerosis and rheumatoid arthritis. Recent developments in molecular biology have permitted an improved resolution of the locus and of the sequential arrangement of the susceptibility determinants on these haplotypes. Restriction fragment length polymorphisms have allowed subdivisions of serological haplotypes to be made. These correlate with disease susceptibility in some cases. Amplification of specific HLA class II alleles and nucleic acid sequencing have resulted in the identification of the structural determinants in the HLA that underlie some of these diseases. PMID- 2894929 TI - Searching for major genes for psychiatric disorders. AB - Many of the major psychiatric disorders show sufficient familial clustering to raise the suspicion that genetic factors are important in determining who is and who is not affected. There is reasonable evidence from many sources to support a major genetic component to these common disorders. However, no simple mode of inheritance can be convincingly demonstrated. A genetic linkage study seems to be the most promising approach towards identifying aetiological factors in these disorders. The neurochemical complexity of the relevant parts of the brain and the absence of any biochemical abnormalities that appear to be aetiologically relevant also give strong impetus for a molecular genetic approach that uses genetic linkage. 'Large-scale' genetic linkage studies using restriction fragment length polymorphisms are under way for manic depressive illness (among other disorders) and are providing evidence against the involvement of some candidate genes. Some strongly positive evidence has also begun to emerge. PMID- 2894931 TI - The human genome sequence and the analysis of multifactorial traits. AB - The human genome probably codes for about 10,000 basic functional units, most of which are functionally related families of genes occurring in one or more closely linked clusters. This relatively limited complexity means that a knowledge of the complete gene sequence is well within our grasp and will be fundamental to the analysis of complex multifactorial traits, including all the major chronic human diseases. Genetic marker segregation among 'affected' individuals in a pedigree, however complex, can now be done by using the essentially unlimited collection of restriction fragment length DNA polymorphisms. This can, in principle, identify all the inherited components of any complex trait and, with a knowledge of the human gene sequence, identify their functional basis. Thus one can now envisage a complete genetic and functional analysis of all complex inherited traits, including the major chronic diseases, and normal variation in physical and behavioural attributes. PMID- 2894932 TI - Structure and evolution of human apolipoprotein genes: identification of regulatory elements of the human apolipoprotein E gene. AB - The structures of the major human apolipoprotein genes have been determined. The genes for apoE, apoC-I, apoC-II, apoC-III, apoA-I, apoA-II and apoA-IV have similar structures, consisting of four exons and three introns, which suggests that they evolved from a common ancestral gene. The third and fourth exons of the ancestral gene appear to have evolved from the duplication of a 66-nucleotide repeat unit that encodes a 22-residue alpha-helical peptide element of amphipathic character. The apoA-I, apoC-III and apoA-IV genes are linked closely within a 20-kilobase (kb) span of chromosome 11. The apoE and apoC-I genes, together with an apoC-I' pseudogene, are linked closely within a 25-kb span of chromosome 19. To characterize potential functional relationships among the apolipoprotein genes, initial studies have been done to identify the molecular elements involved in the regulation of the human apoE gene. Fragments of the 5' flanking portion of this gene were inserted into appropriate plasmid vectors, which contained the bacterial chloramphenicol acetyl transferase gene, and were examined for promoter activity and potential enhancer activity after transfection into cultured mammalian cells. Deletion mapping of the promoter region has identified multiple functional elements, including an enhancer, two G-C boxes (Sp 1 transcription factor binding sites) and an upstream control element. In addition, there is an enhancer located in the first intron. Interactions among these various control elements are likely to determine the ways in which the expression of the apoE gene is regulated. PMID- 2894933 TI - Biochemical tissue markers of human colorectal carcinoma. AB - The potential therapeutic effects of differentiating agents on leukemic and solid tumor cells are being evaluated worldwide. These effects can be followed by morphologic as well as biochemical parameters. The enzymatic profile of four enzymes and the level of carcinoembryonic antigen were studied in 24 human colorectal carcinoma specimens and their adjacent uninvolved mucosa. The enzymes studied were thymidine kinase and 6-phosphogluconate dehydrogenase as markers of proliferation, and alkaline phosphatase and gamma-glutamyl transpeptidase as markers of differentiation. A consistent finding was a marked increase in the activities of thymidine kinase and 6-phosphogluconate dehydrogenase in the tumor cells as compared with the adjacent normal mucosa. The activity of gamma-glutamyl transpeptidase was not significantly different between tumor and uninvolved colon tissue. Alkaline phosphatase activity was markedly reduced in the tumor specimens. A relationship between the degree of differentiation and the degree of penetration and CEA expression was demonstrated in the tumor specimens as well as in their surrounding uninvolved mucosa. PMID- 2894934 TI - Hemorrhoidectomy and sphincterotomy. A prospective study comparing the effectiveness of anal stretch and sphincterotomy in reducing pain after hemorrhoidectomy. AB - The effectiveness of two maneuvers, anal stretch (group 1) and sphincterotomy (group 2), were evaluated in reducing posthemorrhoidectomy pain. The study included 133 patients in group 1 and 125 patients in group 2. Immediate follow-up results showed that 18.4 percent of patients in group 2 required narcotic analgesics in the first 24 hours as compared with 100 percent of group 1 patients (P less than .01). Urinary retention developed in 4 percent of the patients in group 2 and 39 percent of the patients in group 1 (P less than .01). Pain associated with the first postoperative motion was severe in 96.2 percent of those in group 1 as compared with 6.4 percent of patients from group 2 (P less than .01). Moreover, long-term follow-up showed that 57.3 percent of group 1 patients continued to suffer from fecal soiling for ten weeks as compared with 6.4 percent in group 2 who suffered only 4.5 weeks (P less than .01). The routine performance of sphincterotomy through one of the hemorrhoidectomy wounds significantly reduced posthemorrhoidectomy pain and complications. PMID- 2894935 TI - Somatostatin in the idiopathic inflammatory bowel diseases. AB - To study the effect of mucosal inflammation on tissue concentrations of somatostatin, the distribution and concentration of somatostatin in specimens of normal and abnormal (ulcerative colitis and Crohn's disease) ileum and colon were determined by a specific radioimmunoassay. Each tissue specimen obtained at surgery was separated by microdissection into the mucosa-submucosa and the muscularis externa. Immunoreactive somatostatin was acid-extracted from each layer before measurement. Gel chromatography was used to characterize immunoreactive somatostatin measured by radioimmunoassay; somatostatin-28 was the major immunoreactive species measured in human intestine. In normal colon, concentrations of somatostatin were not related to patient age. Concentrations of immunoreactive somatostatin in the mucosa-submucosa of the descending colon were significantly decreased in ulcerative colitis and in Crohn's colitis, compared with normal colon. There was no apparent relationship between concentrations of somatostatin and the duration of inflammatory bowel disease. However, somatostatin concentrations appeared to be lower in patients with severe colitis than in patients with minimal colitis. The decrease in mucosal-submucosal concentrations of somatostatin is in agreement with previous morphologic studies, which have suggested diminished populations of endocrine cells in ulcerative colitis. The possible role of somatostatin in the colon suggests that further studies of the alteration of this gut peptide may be useful in understanding a component of the pathophysiology of idiopathic inflammatory bowel disease. PMID- 2894936 TI - The 1986 Bernard B. Brodie award lecture. The genetic regulation of drug metabolizing enzymes. PMID- 2894937 TI - In vivo 31P nuclear magnetic resonance studies on the absorption of triphenyl phosphite and tri-o-cresyl phosphate following subcutaneous administration in hens. AB - Tri-o-cresyl phosphate (TOCP) and triphenyl phosphite (TPP) are known to be neurotoxic in several species. In a previous study, we found that the subcutaneous administration of the compounds may result in toxicological effects which are prolonged in comparison to administration by other routes. In order to test the hypothesis that slow absorption from the injection site could account for our results, we monitored the disappearance of either compound from the injection site using in vivo 31P nuclear magnetic resonance (NMR). In addition, the test samples and some potential metabolites were examined in vitro with NMR. The disappearance of equimolar doses of subcutaneously injected TOCP (1187 mg/kg) and TPP (1000 mg/kg) from the injection site, with time, showed a biphasic pattern. The first phase took place within a few hours, while the second phase was very slow, with a half-life of about 2 weeks for both compounds. These results may account for the prolonged neuropathy target enzyme inhibition and explain the delayed neurotoxicity produced by subcutaneous injection of TOCP and TPP. Two animals given TPP exhibited an atypical pattern, in that the TPP apparently converted to diphenyl phosphonic acid within several hours of injection. In these hens, this phenomenon was accompanied by acute lethality. The conversion to diphenyl phosphonic acid also took place when the TPP was placed in an aqueous solution in vitro. Diphenyl phosphonic acid may play a role in the unique toxicity of TPP. PMID- 2894938 TI - Induction of sulfamethazine acetylation by hydrocortisone in the rabbit. AB - Daily intravenous administration of hydrocortisone (HC) to rabbits resulted in a marked time-dependent increase in the metabolic clearance of sulfamethazine (SMZ). Kinetic analysis of the plasma concentration-time profiles for SMZ indicated that HC treatment significantly increased the rate of acetylation of SMZ without altering the renal clearances or volumes of distribution for either parent drug or the N-acetyl metabolite N-acetylsulfamethazine (NASMZ). Total body clearance of NASMZ was also unaltered. Doses of HC ranging from 25 to 150 mg/kg were equally effective in enhancing the in vivo acetylation rate of SMZ. Moreover, the induction of SMZ acetylation was reversible when treatment with the steroid was terminated. The in vitro rate of SMZ acetylation was measured in the cytosol of various organs from controls and rabbits treated with HC for 10 days. HC did not alter the Michaelis-Menten parameters for N-acetyltransferase (NAT) activity in kidney, lung, or gut. Similarly, the Km for SMZ acetylation in liver cytosol was not affected by the steroid. However, the Vmax estimates of hepatic NAT activity were significantly increased after HC treatment. At 0.5 mM SMZ and variable [acetyl-CoA], Vmax increased 3-fold from 82 +/- 20 to 244 +/- 43 mumol/min/organ, while at 0.5 mM acetyl-CoA and variable [SMZ], Vmax increased 2.8-fold from 75 +/- 19 to 208 +/- 41 mumol/min/organ. This increase was primarily due to a 69% increase in liver weight since Vmax expressed per mg of cytosolic protein was similar in both groups. The endogenous acetyl CoA concentrations were significantly increased by HC in liver and lung, but not in gut and kidney.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894939 TI - Regional distribution of xenobiotic metabolizing enzymes in respiratory airways of dogs. AB - There is a varied distribution of airway epithelia throughout the respiratory tract that may explain the apparent differential susceptibility of respiratory tract tissues to carcinogens. The objective of this research was to characterize the distribution of xenobiotic metabolizing enzymes in the respiratory tract of the dog and to determine if regional variances in metabolic capability are associated with morphologic differences of surface epithelium among airways. Specific regions from one-half of the nasal, tracheal, bronchial, and pulmonary airways were excised and analyzed for the presence of xenobiotic metabolizing enzymes. Complementary halves of airways were fixed and processed for light microscopy. Substrates for different isozymes of cytochrome P-450, including benzo(a)pyrene, nitropyrene, ethoxycoumarin, and ethoxyresorufin and select Phase II enzymes were measured. The data for benzo(a)pyrene and nitropyrene were qualitatively similar in that there was high metabolic activity in certain regions of the nasal tissue (e.g. ethmoid turbinates) and in the intrapulmonary airway generations 3-18 compared with the major conducting airways (e.g. larynx, trachea, and bronchi). Most ethoxycoumarin O-deethylase activity was in the nasal region with much less activity observed in the major airways or the pulmonary airways. The specific activity of ethoxycoumarin O-deethylase in the ethmoid turbinates was, in general, 5-10 times that observed for the other portions of the nasal cavity sampled. Only the ethmoid turbinates showed evidence of ethoxyresorufin metabolism. Both epoxide hydrolase and glutathione transferase activity was higher in the various tissues of the nasal cavity and in the pulmonary airways compared with the major conducting airways. UDP glucuronyltransferase was relatively evenly distributed throughout the respiratory tract.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894940 TI - Pharmacokinetics of nicotine and 12 metabolites in the rat. Application of a new radiometric high performance liquid chromatography assay. AB - A new radiometric assay for nicotine and 12 of its metabolites disclosed that plasma nicotine and cotinine t1/2 beta were independent of dose after single intraarterial nicotine doses of 0.1, 0.5, or 1.0 mg/kg. At high doses, nicotine AUC and clearance tended to exhibit a small degree of dose dependency. The longest lived metabolites, cotinine-N-oxide and a previously unidentified metabolite now revealed to be allohydroxydemethylcotinine, persisted for 96 hr after nicotine injection, whereas cotinine was detected for only 48 hr. Cotinine, formerly considered the longest lived nicotine metabolite, serves widely as the most sensitive indicator of prior exposure to small concentrations of nicotine. The present studies disclose new, longer lasting metabolites that may perform this function more sensitively, at least in the rat. At the 3 doses of nicotine administered, plasma nicotine half-life ranged from 0.9 to 1.1 hr; total body clearance of nicotine ranged from 2.9 to 3.9 liters.hr-1.kg-1; and apparent volume of distribution of nicotine from 4.7 to 5.7 liters.kg-1. Also at these 3 doses, mean half-lives of urinary excretion of cotinine, cotinine-N-oxide, and allohydroxydemethylcotinine ranged from 4.8 to 5.3 hr, from 7.9 to 8.2 hr, and from 9.9 to 11.0 hr, respectively. PMID- 2894941 TI - Disposition of cefixime in the pregnant and lactating rat. Transfer to the fetus and nursing pup. AB - The disposition of cefixime, a potent, third generation, orally active cephalosporin, was characterized in the pregnant and lactating rat. After a single iv dose of 17.8 mg/kg 14C-cefixime to day 18 pregnant rats, the half-life for elimination of radioactivity from both maternal serum and placentas was 6.9 hr. Elimination from fetal plasma and tissues was somewhat longer, 12.5 and 13.7 hr, respectively. However, comparison of areas under the curve indicated that exposure of the fetuses to cefixime was far less than that of placentas. Whole body autoradiography showed the greatest radioactivity in maternal liver, kidney, and intestines. In the lactating rat, steady state plasma concentrations of 14C cefixime were achieved by continuous ip infusion of 2.54 mg/kg/day via Alza osmotic Mini-pumps from days 10 to 14 postpartum. Plasma concentrations of radioactivity in the dams were, on the average, 70 times greater than in their nursing pups throughout the study. After 102 hr of drug infusion, total radioactivity in the body of the pups, including the stomach and intestinal contents, was 1% of the 14C-cefixime estimated to be in the mother's body at steady state. Overall, these data indicate that exposure of the developing rat fetus and nursing pup to cefixime after maternal drug administration is quantitatively small. PMID- 2894942 TI - Potential metabolic basis for enflurane hepatitis and the apparent cross sensitization between enflurane and halothane. AB - Clinical case reports of unexplained hepatic dysfunction following enflurane and isoflurane anesthesia led to the hypothesis that oxidative metabolism of these drugs by cytochromes P-450 produces immunoreactive, covalently bound acylated protein adducts similar to those implicated in the genesis of halothane-induced hepatic necrosis. Microsomal adducts were detected by enzyme-linked immunosorbent assay and immunoblotting techniques utilizing specific anti-trifluoroacetyl (TFA) IgG hapten antibodies in rat liver following enflurane, isoflurane, or halothane administration. Preincubation of the antibodies with microsomes from halothane pretreated rats or with 500 microM TFA-lysine, markedly inhibited adduct recognition, while preincubation with 500 microM acetyllysine had no effect. The relative amounts of immunoreactive protein adducts formed were halothane much greater than enflurane much greater than isoflurane and correlates directly with the relative extents of metabolism of these agents. These results support the view that acyl metabolites of the volatile anesthetics may become covalently bound to hepatic proteins, thus serving as antigens, and thereby account for the apparent cross-sensitization and idiosyncratic hepatotoxicity reported for these drugs. PMID- 2894943 TI - Pharmacokinetics and toxicity of high doses of antibody Fab fragments in rats. AB - The treatment of drug toxicity with drug-specific antibody fragments may, for some compounds, require very high doses of antibody fragments. To examine the feasibility of this therapeutic approach, the pharmacokinetics and toxicity of high doses of nonspecific human IgG Fab fragments were studied in rats. Six animals received 7.5 g/kg iv Fab over 1 hr. Maximum serum Fab concentration was 42.1 +/- 9.9 mg/ml. Calculated pharmacokinetic parameters included steady state volume of distribution 0.43 +/- 0.06 liter/kg, t/2 alpha 2.4 +/- 1.4 hr, t/2 beta 16.3 +/- 2.4 hr, and systemic clearance 27.2 +/- 4.4 ml/hr/kg. Urinary excretion accounted for 31.8 +/- 7.5% of the administered dose. These values are similar to those previously reported for much lower doses (5-15 mg/kg) of digoxin-specific Fab fragments in dogs, baboons, and humans. All animals tolerated Fab infusion without changes in blood pressure, heart rate, or electrocardiogram. The serum creatinine concentration and urinary protein excretion were unchanged 1 week after Fab administration. One animal developed a self-limited respiratory illness 1 week after Fab administration, probably because of intercurrent infection. Organ histology 2 weeks after Fab administration was normal in all animals. These data suggest that rapid iv administration of high doses of antibody Fab fragments is feasible and support the potential use of high doses of Fab fragments as a therapy for drug toxicity. Although the possibility of dose-dependent kinetics was not studied, the similarity of the pharmacokinetics of this high Fab dose in the rat to that of lower doses in other species further suggests that the rat may be a suitable species for studying Fab-drug interactions. PMID- 2894945 TI - In vitro evidence against the oxidation of quinidine by the sparteine/debrisoquine monooxygenase of human liver. AB - Competitive inhibition studies using human liver microsomes have shown that quinidine (QD) has an exceptionally high affinity (60 nM) for the genetically variable cytochrome P-450 that catalyzes the formation of 4-hydroxydebrisoquine and dehydrosparteines from debrisoquine and sparteine. The present study examined the effect of sparteine and debrisoquine on the oxidation of QD by microsomes prepared from two human livers. QD and its major metabolite 3-hydroxy-QD were measured by quantitative TLC. QD 3-hydroxylation followed saturable single-site kinetics over a 1-250 microM range of QD concentrations. The Km and Vmax of the reaction in the two liver specimens were 47.5 +/- 3.5 microM and 58.7 +/- 5.9 microM, and 0.36 +/- 0.08 and 0.29 +/- 0.02 nmol of 3-hydroxy-QD/mg of protein/min. Sparteine and debrisoquine (250 microM) had no effect on this QD 3 hydroxylase activity. Furthermore, near-saturation of the sparteine/debrisoquine isozyme by 250 microM sparteine had no effect on the oxidation of QD by all routes (measured by QD disappearance from an initial level of 70 nM during an 8 hr incubation period). These observations indicate that none of the major oxidative reactions of QD are catalyzed by the sparteine/debrisoquine isozyme; QD may simply bind to this cytochrome P-450, without being oxidized by it. PMID- 2894944 TI - Metabolic inhibition and di-2-ethylhexyl phthalate pharmacokinetics in fish. AB - A pharmacokinetic model for the accumulation of di-2-ethylhexyl phthalate (DEHP) by sheepshead minnow predicted a significant increase in the bioconcentration factor (BCF) of DEHP if its metabolism were inhibited. To test this prediction, fish were treated with either piperonyl butoxide (PBO) or bis-(p nitrophenyl)phosphate (BNPP) before and during their exposure to DEHP. Compared with the controls, the PBO-treated fish showed no significant differences in either the amount of total metabolites in the fish and exposure water or the amount of DEHP in the fish. Conversely, the total amount of metabolites formed by BNPP-treated fish was only 23% of that in the control. This indicated that hydrolysis was a major pathway for DEHP metabolism in sheepshead minnow. The amount of DEHP accumulated by the BNPP-treated fish was almost twice that of the controls, which also agreed with the model prediction. A pharmacokinetic analysis of the time course of DEHP accumulation and metabolism indicated that BNPP altered the dynamics of DEHP in the fish beyond simply reducing the metabolic clearance. BNPP reduced the value of the absorption clearance to half that of the control, and the phthalate appeared to distribute more rapidly to the poorly perfused tissues. These effects may have been caused by the anticholinesterase activity of BNPP. The model-predicted BCF of DEHP in BNPP-treated fish was more than 6 times the control value, apparently as a consequence of decreased metabolic clearance and increased volume of distribution. PMID- 2894946 TI - Characterization of mixed-function oxidases and purified cytochrome P-450 of livers of house musk shrew, Suncus murinus. AB - Characteristics of mixed-function oxidases in the liver of house musk shrew, Suncus murinus, were studied. The basal level of cytochrome P-450 and the activity of drug-metabolizing enzyme in hepatic microsomes of Suncus murinus is relatively lower than that of rats, while the level of cytochrome b5 and NADPH cytochrome c reductase is approximately the same as that of rats. The treatment of Suncus murinus with phenobarbital and 3-methylcholanthrene elevated the level of cytochrome P-450 and the activity of drug-metabolizing enzymes, but not the level of cytochrome b5. Two distinct forms of cytochrome P-450 have been purified from hepatic microsomes of 3-methylcholanthrene-treated Suncus murinus. These forms have their absorption maximum at 448.0 nm and 448.5 nm in CO-bound reduced form, and one is in the high-spin state and the other is in the low-spin state. They are different in their molecular weights (53,500 and 55,000) and in their spectral and catalytic properties. Characteristics of these forms were compared with those of the major forms of cytochrome P-450 purified from livers of rats treated with 3-methylcholanthrene. PMID- 2894947 TI - Enzymatic oxidation of 7-hydroxylated delta 8-tetrahydrocannabinol to 7-oxo-delta 8-tetrahydrocannabinol by hepatic microsomes of the guinea pig. AB - Hepatic microsomes of the guinea pig converted delta 8-tetrahydrocannabinol (delta 8-THC) to various oxidized metabolites, including 7 alpha-hydroxy-delta 8 THC (7 alpha-OH-delta 8-THC), 7 beta-OH-delta 8-THC, and 7-oxo-delta 8-THC. The enzyme which mediates biotransformation of 7-OH-delta 8-THCs to 7-oxo-delta 8-THC was characterized in the present study. The oxidative activity was mainly located in microsomes. The microsomal reaction required NADPH and oxygen and showed an optimal pH around 7.5. The reaction was inhibited by beta-diethylaminoethyl diphenylpropylacetate (SKF 525-A), an inhibitor of cytochrome P-450, but not by pyrazole, a specific inhibitor of alcohol dehydrogenase. However, 7-oxo-delta 8 THC formation was not affected by carbon monoxide or by pretreatment of animals with cobaltous chloride (40 mg/kg, ip, once a day for 3 days). Atmospheric oxygen was incorporated into 7-oxo-delta 8-THC formed from 7 alpha-OH-delta 8-THC, but not into that from 7 beta-OH-delta 8-THC. Further, 7-oxo-delta 8-THC formed from 7 alpha-18OH-delta 8-THC released about half of 18O at the 7-position, whereas the 7-oxo metabolite from 7 beta-18OH-delta 8-THC lost little of the isotope at the 7 beta-position during the oxidative reaction. From these results, it is likely that hepatic microsomal monooxygenase (probably cytochrome P-450) plays a main role in the oxidation. In addition, mechanisms for 7-oxo-delta 8-THC formation from 7 alpha-OH-delta 8-THC or 7 beta-OH-delta 8-THC are different. PMID- 2894948 TI - The effect of N-acetylcysteine on the toxicity induced by N-nitrosodimethylamine. PMID- 2894949 TI - Interspecies comparison of acivicin pharmacokinetics. AB - Pharmacokinetic studies with the amino acid antineoplastic agent, acivicin, were carried out in the Sprague-Dawley rat, cynomolgus monkey, and beagle dog. Data were analyzed together with previously published studies in the mouse and rhesus monkey. Log-log plots of body weight (B, kg) versus total body clearance (ClB, ml/min), elimination half-life (t1/2, hr), and volume of distribution (V, ml) in the five species were linear with high correlation coefficients (r greater than or equal to 0.98) despite large differences in the extent of nonrenal clearance in the various species (ranging from approximately 30% of the dose in the mouse to 90% in the dog). Linear regression on the plots yielded allometric expressions (ClB = 4.0 x B0.62; t1/2 = 1.8 x B0.31; V = 620 x B0.95) which were extrapolated mathematically to predict acivicin pharmacokinetic parameters in humans prior to the first clinical trials. Predicted versus measured (mean +/- SD, N = 21 patients) pharmacokinetic values in humans were: ClB (ml/min), 50 vs. 49 +/- 13; t1/2 (hr), 6.4 vs. 9.5 +/- 3.5; VB (ml/kg), 500 vs. 580 +/- 110. Thus, the animal data were successfully extrapolated to yield reasonable predictions of human pharmacokinetic parameters, despite varying extents of renal and nonrenal clearance in the species examined. With one exception, plasma concentration-time data in six species spanning a 3000-fold body weight range and a 120-fold dose range were plotted on a single curve after plasma concentrations were normalized for the dose administered and chronological times were adjusted for body weight to yield "physiological times."(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894950 TI - The effects of tin-protoporphyrin administration on hepatic xenobiotic metabolizing enzymes in the juvenile rat. AB - The heme analogue tin-protoporphyrin IX (SnP) is a potent inhibitor of microsomal heme oxygenase. Administration of SnP to neonatal rats can prevent hyperbilirubinemia by blocking the postnatal increase of heme oxygenase activity. Apparently innocuous at therapeutic doses, it is of potential clinical value for chemoprevention of neonatal jaundice. We found that when 50-g male Sprague-Dawley rats were treated daily with 50 mumol of SnP/kg sc for 6 days, hepatic microsomal cytochromes b5 and P-450 were significantly diminished. Cytochrome P-450 reductase, two P-450-dependent monooxygenases, aminopyrine demethylase and benzo(a)pyrene hydroxylase, and catalase, a peroxisomal hemoprotein, were also significantly diminished. These results suggested that SnP might significantly affect the metabolism of other xenobiotics. This possibility was confirmed by the finding that hexobarbital-induced sleep lasted 4 times longer in SnP-treated rats than in controls. Inhibition of protein synthesis by SnP was ruled out as the cause of hemoprotein loss when administration of [3H]leucine to SnP-treated and control rats demonstrated that proteins of the microsomal, cytosolic, and plasma membrane fractions of the livers from both groups incorporated similar levels of leucine. When 55FeCl3 and [2-14C]glycine were administered to measure heme synthesis, heme extract from the livers of SnP-treated rats contained 4 times more label from iron and glycine than did heme from control livers. Despite the apparent increased rate of heme synthesis in SnP-treated rats, each of the three cell fractions demonstrated a significant loss of heme but contained sizable amounts of SnP. These findings suggest that SnP causes a decrease of functional hemoprotein and partial loss of enzymic activity by displacing intracellular heme. PMID- 2894951 TI - Polyethylene glycol-L-asparaginase and L-asparaginase studies in rabbits. AB - Injections of polyethylene glycol (PEG)-L-asparaginase or L-asparaginase were given to two rabbits each at doses of 40 units/kg. Ten min following injection of either enzyme preparation, the plasma enzyme concentration was approximately 1 unit/ml. This level decreased steadily in the rabbits given L-asparaginase, with a t1/2 of approximately 20 hr. In contrast, the enzyme level in rabbits given PEG L-asparaginase decreased much more slowly, with a t1/2 of approximately 144 hr. The slower disappearance rate of PEG-L-asparaginase resulted in greater values for the area under the concentration versus time curve and smaller values for total clearance. Immediately following the enzyme injections, no L-asparagine could be detected in the plasma, and a transient elevation of L-aspartic acid levels was noted. By 4 hr, the L-aspartic acid level in all of the rabbits returned to near normal. The L-asparagine, however, was not measurable as long as plasma enzyme was detectable. Levels of L-asparagine returned to normal 4 days after L-asparaginase administration, and 27 days elapsed before L-asparagine was detected in rabbits given PEG-L-asparaginase. PMID- 2894952 TI - UDP-glucuronosyltransferase activity toward digitoxigenin-monodigitoxoside. Differences in activation and induction properties in rat and mouse liver. AB - Glucuronidation of digitoxigenin-monodigitoxoside (DT1), a metabolite of the cardiac glycoside digitoxin, is mediated by the microsomal isozymes, UDP glucuronosyltransferase(s) (UDP-GT). The present studies examined the activation and induction properties of UDP-GT activity toward DT1 in hepatic microsomes of rats and mice. When compared to enzyme activity present in native (latent) microsomes of the rat (0.104 +/- 0.010 nmol/min/mg of protein), the activity toward digitoxigenin-monodigitoxoside in mouse native microsomes was 3.5-fold higher (0.379 + 0.44 mumol/min/mg of protein). After treatment with ionic (sodium cholate), zwitterionic [3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid (CHAPS)], or nonionic (Emulgen 911, Triton X-100) detergents, or with UDP-N acetylglucosamine, enzyme activity in rat microsomes remained unchanged. In contrast, UDP-GT activity (DT1) in mouse liver microsomes treated with detergents or with the nucleotide was increased 2-3-fold above native enzyme activity. Pretreatment of rats with the microsomal enzyme inducers, 3-methylcholanthrene and phenobarbital, had no effect on this enzyme activity, whereas pretreatment with pregnenolone-16 alpha-carbonitrile (PCN) and dexamethasone (DEX) increased enzyme activity toward DT1 800 and 380%, respectively. These findings support the hypothesis that PCN and DEX induce a unique form of UDP-GT in the rat that selectively glucuronidates DT1. In marked contrast, the activity of this enzyme in mouse liver was not affected by pretreatment with any of the microsomal inducers, including PCN and DEX. In both rat and mouse, the P-450p-dependent N ethylmorphine demethylase activity was increased 10-15-fold in PCN-pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894954 TI - Effect of monooxygenase inducers and inhibitors on the hepatic metabolism of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat and hamster. AB - The rat and hamster exhibit about a 100-fold difference in sensitivity to the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), with the hamster representing the most resistant species examined to date. The present study compared the induction and inhibition of hepatic TCDD metabolism in these species using suspensions of isolated hepatocytes. Purified 14C-TCDD or 3H-TCDD (2.2 microM) was incubated for 2-6 hr with hepatocytes isolated from untreated, TCDD pretreated (5 micrograms/kg, ip), 3-methylcholanthrene-pretreated (3-MC, 50 mg/kg, ip, x 3 days), isosafrole-pretreated (ISO, 150 mg/kg, ip, x 3 days), or phenobarbital-pretreated (PB, 80 mg/kg, ip, x 3 days) rats and hamsters. Untreated rat and hamster hepatocytes metabolized TCDD at a similar rate (0.20 and 0.18 pmol/hr/mg, respectively). In both species, TCDD and 3-MC pretreatments elevated the rate of TCDD metabolism by 5-6-fold, while PB pretreatment had no effect. isosafrole modestly increased (1.8-2.5-fold) TCDD metabolism in each species. Analysis by high performance liquid chromatography indicated similarities in the TCDD-metabolite profiles formed by hepatocytes from both species, with two major metabolite peaks detected following induction by TCDD and 3-MC. The in vitro metabolism of TCDD in hepatocytes from TCDD-pretreated rats and hamsters was inhibited by 7,8-benzoflavone (100 microM), but not by metyrapone (100 microM). The effect of these cytochrome P-450 inducers and inhibitors on the metabolism of 3H-benzo(a)pyrene (BaP) in rat hepatocytes was similar to their effect on TCDD metabolism. However, marked differences were observed in their effects on the metabolism of BaP and TCDD in hamster hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894953 TI - Inhibition of rat liver aldehyde dehydrogenases by acrolein. AB - Acrolein, the lowest member of the ethylenic aldehyde series, has been widely studied as a result of the diverse toxicities associated with it. Previous investigations into the enzymatic process responsible for the detoxification of acrolein implicated rat liver aldehyde dehydrogenase (ALDH) in the oxidation of this aldehyde. Contrary to these reports, in our investigation we were unable to detect the oxidation of acrolein to acrylic acid by Sprague-Dawley rat liver mitochondrial or cytosolic ALDHs measured spectrophotometrically by the production of NADH, or by HPLC analysis for the production of acrylic acid. However, in the course of these experiments, it was demonstrated that acrolein is a potent inhibitor of rat liver ALDHs. Mitochondrial and cytosolic high affinity ALDHs are particularly sensitive to the inhibitory effects of acrolein. The type of inhibition exhibited by these high affinity ALDHs is primarily irreversible, with a slight degree of reversible noncompetitive inhibition. The inhibition is rapid with a 91 and 33% reduction in control mitochondrial and cytosolic ALDH activities, respectively, with a 5-sec preincubation of 30 microM acrolein prior to the addition of the aldehyde substrate. Significant inhibition of total (high plus low affinity isozymes) mitochondrial and cytosolic ALDHs occurs only at relatively high acrolein concentrations (greater than or equal to 50 microM). The inhibition displayed by the total mitochondrial and cytosolic ALDHs is mixed type, with both reversible noncompetitive and irreversible inhibition demonstrated. PMID- 2894955 TI - Kinetic studies on the competition between famotidine and cimetidine in rats. Evidence of multiple renal secretory systems for organic cations. AB - The H2-receptor antagonists famotidine and cimetidine are both basic drugs that are predominantly eliminated by the kidneys. Cimetidine has been shown to inhibit the renal secretion of tetraethyl-ammonium bromide (TEAB) but not p-aminohippuric acid (PAH), suggesting that cimetidine is secreted by an organic cation transport system [Weiner and Roth: J. Pharmacol. Exp. Ther. 216: 516 (1981)]. The present study shows that famotidine behaves like cimetidine in that it also inhibits TEAB but not PAH excretion. Where a high concentration of cimetidine in plasma has an inhibitory effect on the renal excretion of famotidine, the reverse is not true, i.e. high plasma levels of famotidine have no effect on the excretion of cimetidine. Further evidence that additional transport systems are involved in the renal tubular secretion of cimetidine is as follows. Quinine, a potent competitor of the organic cation transport system, inhibits the secretory component of famotidine renal clearance but not that of cimetidine. Probenecid, a classic competitor for the organic anion transport system, inhibits the renal excretion of cimetidine but not famotidine. However, the effect of probenecid is minor and not sufficient to account for other components of cimetidine secretion not affected by famotidine and quinine. PMID- 2894956 TI - Cyclosporine-cimetidine interaction. AB - Cyclosporine (CsA) is used to prevent rejection of transplanted organs. It is extensively metabolized in the liver by the mixed function oxidase enzyme system by demethylation and hydroxylation. Since cimetidine is a widely prescribed H2 antagonist drug which is known to inhibit the P-450 enzyme system, we studied the effect of chronic treatment with cimetidine on CsA by determining the disposition of CsA (15 mg/kg, iv), prior to and after chronic treatment with cimetidine (60 mg/kg, po), for 5 days. CsA was determined by an HPLC procedure. The clearance (Cl) of CsA was significantly reduced following treatment with cimetidine when compared to the Cl value obtained in the control group (15.46 versus 10.36 ml/min/kg). There were no significant changes in the volume of distribution of CsA, one reason being that cimetidine and cyclosporine bind to different proteins. From the results obtained, we conclude that since cimetidine is an inhibitor of the mixed function oxidase system enzyme system, it inhibits the metabolism of CsA. PMID- 2894957 TI - Metabolism of 2,3-dichloro-1-propene in the rat. Consideration of bioactivation mechanisms. AB - At the present time, comprehensive metabolism studies of 2,3-dichloro-1-propene (2,3-DCP) have not yet been reported. We have investigated the biotransformation of 2,3-DCP using female Wistar rats in order to elucidate the bioactivation mechanisms. 175 mg/kg, 1,3-14C-2,3-DCP in corn oil was administered to a rat. The animal was killed 20 hr later. Approximately 56.7% of the radioactivity was excreted in the urine, 1.6% in the feces, 5.3% was exhaled as unchanged 2,3-DCP, and 0.3% as CO2. 31.3% remained in the organs and the carcass. Three metabolic pathways were established. 1) Conjugation with GSH leading to S-(2-chloro-2 propenyl)mercapturic acid. 2) The P450 induced epoxidation with subsequent rearrangement to highly mutagenic 1,3-dichloroacetone. 1,3-Dichloroacetone was further converted to the dimercapturic acid, 1,3-(2-propanone)-bis-S-(N acetylcysteine). 3) The hydrolysis to 2-chloroallyl alcohol followed by alcohol dehydrogenase catalyzed formation of highly mutagenic 2-chloroacrolein. The 2 chloroallyl alcohol is excreted directly in the urine and as the glucuronide. 2 Chloroacrolein is further oxidized to 2-chloroacrylic acid which is also excreted in the urine. PMID- 2894958 TI - Metabolism of bepridil in laboratory animals and humans. AB - The metabolism of bepridil was studied in the Swiss mouse, Sprague-Dawley rat, New Zealand rabbit, rhesus monkey, and healthy human. After oral administration of bepridil-14C-hydrochloride, recoveries of total radioactivity in urine and feces (7 days) were greater than or equal to 80% of the administered dose in all five species. Bepridil and 25 metabolites have been isolated by HPLC and TLC from representative plasma, urine, and fecal extract pools from all species and identified on the basis of TLC, HPLC, and mass spectrometry. The identified metabolites explained 60-99% of the total radioactivity in each sample for rabbit plasma, in which only 17% of the total radioactivity was characterized. Metabolic pathways involving oxidative reactions at seven sites on the bepridil molecule are proposed for each species. Metabolite formation in the five species is described by four interrelated pathways. The metabolic pathway involving aromatic hydroxylation followed by N-dealkylation, N-debenzylation, and N-acetylation was important in all species. Major metabolites produced by this pathway included 4 hydroxy(at N-phenyl)-bepridil (Ia), N-benzyl-4-amino-phenol (IV), and N-acetyl-4 aminophenol (Vy). Metabolite Ia was isolated in significant amounts (greater than or equal to 5% of sample) in all fecal and urine samples except rat urine. Metabolite IV was a major circulating metabolite in all species and a major urinary metabolite in humans. Metabolite Vy was present in significant quantities in urine in all species except rabbit. Other important pathways involved primary reactions such as iso-butyl hydroxylation, pyrrolidine ring oxidation, and N debenzylation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894959 TI - 19F NMR spectrometry evidence for bile acid conjugates of alpha-fluoro-beta alanine as the main biliary metabolites of antineoplastic fluoropyrimidines in humans. AB - The human biliary excretion of antineoplastic fluoropyrimidines was studied using 19F NMR. This method allows a direct detection of all the fluorinated metabolites of a fluorinated drug and requires no labeled compound. From a patient with an external bile derivation, treated with 5'-deoxy-5-fluorouridine (5'dFUrd), the biliary excretion of 5'dFUrd metabolites was low (0.8% of the injected dose) and made up of alpha-fluoro-beta-alanine (FBAL) and fluoride ion (F-) which represented approximately equal to 10% of the excreted metabolites and approximately equal to 90% of unknown metabolites. These unknown metabolites were conjugates of FBAL with the two "primary" bile acids only present in the bile of patients with an external bile drainage, i.e. cholic and chenodeoxycholic acids, in a 3:1 ratio. In the bile obtained at surgery from a patient treated with intrahepatic 5-fluorouracil, the major metabolites were conjugates of FBAL with the three major bile acids of human bile, i.e. cholic, deoxycholic, and chenodeoxycholic acids. Moreover, 19F NMR showed that only one of the two diastereoisomers of each conjugate of FBAL with bile acids was formed in vivo, confirming that metabolic FBAL is optically active. PMID- 2894960 TI - Biliary excretion of a glutathione conjugate of busulfan and 1,4-diiodobutane in the rat. AB - gamma-Glutamyl-beta-(S-tetrahydrothiophenium)alanyl-glycine, the glutathione sulfonium conjugate of busulfan and 1,4-diiodobutane, was identified in the bile of rats following intravenous administration of equimolar doses of either compound. The glutathione-sulfonium conjugate was synthesized from 1-bromo-4 chlorobutane and characterized by 1H and 13C NMR and FAB/MS. An HPLC method was developed to identify the conjugate from rat bile by pre-column fluorescent derivatization with o-phthalaldehyde. The biliary excretion of cyclic sulfonium conjugates was quantitated indirectly by measuring the release of tetrahydrothiophene (THT) after treatment of the bile with base. THT release was quantitative and was measured by gas chromatography. With busulfan, peak biliary concentrations of THT-releasing metabolite(s) were reached after 90 min and 26% of the dose of busulfan was recovered in the bile after 8 hr. When diiodobutane was administered, 21% of the dose was recovered, and the peak concentration was reached in 30 min. The decline in THT releasing metabolite(s) was more rapid with 1,4-diiodobutane, and THT was no longer measurable after 3.5 hr compared to 7.5 hr after busulfan administration. These data confirm that busulfan and other 1,4 disubstituted butanes are conjugated with glutathione in vivo. PMID- 2894961 TI - l-alpha-Acetylmethadol administration to lactating rat dams. Effect on hepatic aniline hydroxylase and ethylmorphine N-demethylase activities in rat pups. AB - l-alpha-Acetylmethadol (LAAM) was administered to lactating rat dams, and subsequent effects on hepatic drug-metabolizing enzymes of their offspring were assessed. Dams were given LAAM or a control solution in their drinking water following parturition and throughout lactation. Hepatic ethylmorphine-N demethylase (EMDM) and aniline hydroxylase (AH) activities, as well as cytochrome P-450 content, were determined in the offspring at 21-23 days of age, or following sexual maturation (61-64 days). LAAM induced AH and EMDM activities, as well as cytochrome P-450 content in both male and female 21-23-day-old pups compared to controls; these differences were not observed at 61-64 days of age. In addition, normal sex-related differences in EMDM activity were apparent at 61 64 days of age. These results demonstrate the LAAM administration to lactating dams causes hepatic metabolic induction in the sexually immature rat, suggesting that LAAM and/or its metabolites passed to the pups via the milk. These changes, induced by LAAM administered via lactation, are reversible and do not interfere with the normal development of sex-dependent differences in hepatic EMDM activity observed in rats following sexual maturation. PMID- 2894962 TI - Neonatal programming of ethylmorphine demethylase and corticosteroid 5 alpha reductase by testosterone, dihydrotestosterone, and estradiol. Effects of an anti estrogen, an anti-androgen, and an inhibitor of estrogen synthetase. AB - The neonatal imprinting of ethylmorphine demethylase and corticosteroid 5 alpha reductase was studied. Males, castrated at birth (day 1), were injected (sc) with testosterone, dihydrotestosterone, or estradiol on days 2, 4, and 6 and with testosterone (2 mg/rat/day) on days 50-59. Microsomes were prepared on day 60. All three steroids, at greater than or equal to 0.73 mumol/pup, increased the apparent Vmax and decreased the apparent Km of the demethylase to values that did not differ (p less than 0.05) from those of intact adult males. Analogously, all steroids, at greater than or equal to 0.73 mumol/pup, decreased the apparent Vmax of the reductase to intact male values; its apparent Km was increased to adult male values by both androgens (at greater than or equal to 0.37 mumol/pup) and by estradiol (at greater than or equal to 0.73 mumol/pup). Flutamide (1.45 mumol/pup) failed to alter these effects indicating that androgen receptors are not involved in the imprinting process. Nafoxidine (1.45 mumol/pup) blocked the effects of all three steroids, indicating that androgens and estrogens both imprint via the estrogen receptor. An inhibitor of androgen aromatase, 1,4,6 androstatriene-3, 17 dione, blocked the imprinting effects of testosterone, but not those of dihydrotestosterone. Thus, testosterone is oxidized to estradiol prior to imprinting, while dihydrotestosterone imprints as the parent compound. The latter may reflect a pharmacologic occupancy of the estrogen receptor by dihydrotestosterone. PMID- 2894963 TI - Interaction of epicatechins derived from green tea with rat hepatic cytochrome P 450. AB - Green tea has been used for generations in China and Asia as an antipyretic and diuretic. Prior studies have shown that extracts of green tea inhibit the mutagenicity of polycyclic aromatic hydrocarbons and aflatoxin B1. In this study, we investigated the interaction of certain flavonoid components of green tea epicatechin derivatives including (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG), and (-)-epigallocatechin-3-gallate (EGCG) with rat hepatic microsomal cytochrome P-450 (P-450). The addition of EC, EGC, ECG, and EGCG to hepatic microsomes prepared from phenobarbital (PB)-treated rats resulted in spectral changes characterized by absorbance maxima at 420 nm and minima at 380 nm, typical of modified Type II (reverse Type I) binding. Of the epicatechin derivatives, EGCG and ECG showed greater spectral change with oxidized P-450 and time- and concentration-dependent inhibition of the binding of carbon monoxide to dithionite-reduced cytochrome P-450. The addition of EC, EGC, ECG, and EGCG to microsomes prepared from control, PB- or 3-methylcholanthrene treated rats resulted in a dose-dependent inhibition of cytochrome P-450 dependent aryl hydrocarbon hydroxylase, 7-ethoxycoumarin O-deethylase, and 7 ethoxyresorufin O-deethylase activities. EGCG was the most potent in this regard. Green tea polyphenols and epicatechin derivatives also significantly inhibited NADPH-cytochrome c reductase activity. An examination of the structure activity relationship of epicatechin derivatives suggests that the inhibitory effect on the microsomal enzyme system may be due to the galloyl groups or hydroxyl groups on the molecule. Our data indicate that these extracts of green tea may have potential as anticarcinogens. PMID- 2894964 TI - Treatment of severe cryptosporidium-related diarrhea with octreotide in a patient with AIDS. AB - Cryptosporidiosis commonly causes severe diarrhea in immunosuppressed patients. There currently are no antiparasitic drugs consistently effective for this infection. This case describes a 26-year-old hemophiliac patient with acquired immunodeficiency syndrome and cryptosporidiosis whose diarrhea improved with continuous intravenous administration of a long-acting somatostatin analog, octreotide. Somatostatin has a variety of inhibitory effects on gastrointestinal hormones as well as a possible nonspecific effect on gastrointestinal mucosal fluid and electrolyte secretion. The somatostatin analog should be considered for patients with secretory diarrhea refractory to other forms of therapy. PMID- 2894966 TI - Agranulocytosis associated with sulfasalazine. AB - Agranulocytosis is a rare but potentially lethal adverse effect of sulfasalazine. We report a case of sulfasalazine-associated agranulocytosis that occurred in a 79-year-old woman who had been taking the drug for approximately seven weeks. The patient had discontinued the drug on her own initiative nine days prior to admission. The patient was admitted with complaints of hoarseness, fever, odynophagia, and malaise. The total white blood cell count was 600/mm3 with a differential of 0% neutrophils, 8% bands, 67% lymphocytes, and 25% monocytes; a bone marrow aspirate and biopsy revealed maturation arrest. The patient's peripheral white blood cell count and differential progressively increased over the nine-day hospital course. Upon discharge the white blood cell count was 12,000 cells/mm3 with 66% neutrophils, 8% bands, 16% lymphocytes, and 10% monocytes. Complete blood counts should be performed periodically in patients receiving sulfasalazine, especially during the first two months of therapy. Pharmacists should counsel patients to discontinue the drug and consult their physician immediately if they develop unexplained fever, chills, sore throat, malaise, or other nonspecific illness during the initial two months of treatment. PMID- 2894965 TI - Remission of symptoms of chemotherapy-refractory metastatic insulinoma using octreotide. AB - The symptoms resulting from the hyperinsulinemia of severe refractory metastatic insulinoma were palliated using self-administered divided doses of a long-acting minisomatostatin analog, octreotide. The substance was well tolerated and the attributable side effects were minimal (primarily gastrointestinal complaints). There were significant improvements in peripheral edema, ascites, and serum electrolytes throughout therapy. Serum insulin and glucagon levels were largely unchanged. Computed tomography scans performed during therapy showed stabilization of pancreatic and hepatic disease. Severe, recurrent hypoglycemic episodes due to hyperinsulinemia were reduced both in number and severity for almost a three-month period. This allowed the elimination or reduction of other chronic, supportive medications and improved quality of life. PMID- 2894968 TI - Somatostatin and octreotide: literature review and description of therapeutic activity in pancreatic neoplasia. AB - The somatostatins represent endogenous substances that serve a diversity of functions in the body. These activities are just beginning to be understood and could have major implications in the treatment of human disease. Their chief pharmacologic activities lie in the modification or modulation of protein hormone synthesis of the gastrointestinal system; a great many other systems may be involved as well. Since the discovery of the therapeutic potentials of naturally isolated somatostatins, attempts have been made to design newer analogs more conducive to practical use. Such an example is long-acting somatostatin analog octreotide. Literature has recently begun to appear describing the therapeutic activities of this and other similar compounds and the first steps to understanding their clinical pharmacology are being taken. Surprising activity has been found in the palliative treatment of a wide variety of formerly resistant gastrointestinal syndromes and endocrine tumors. These activities may have considerable future impact on the treatment of disease involving hormonal imbalance or inappropriate secretion. PMID- 2894967 TI - Octreotide: entering the new era of peptidomimetic therapy. PMID- 2894969 TI - [Therapeutic achlorhydria: for which diseases, when and for how long?]. PMID- 2894970 TI - Effects of chlorcyclizine-induced glycosaminoglycan alterations on patterns of hyaluronate distribution during morphogenesis of the mouse secondary palate. AB - Chlorcyclizine (CHLR) enhances the degradation of hyaluronate (HA) into smaller molecular weight pieces with no effect on its synthesis. Administration of CHLR to pregnant CD-1 mice on gestational days 10.5, 11.5 and 12.5 results in 100% cleft palate in the fetuses. The caudal two thirds of the palatal shelves are reduced in size and unable to reorient in vitro, while anterior shelf regions are relatively unaffected. Alcian blue staining combined with specific enzymic digestion was used to identify HA in sections of CHLR-treated shelves. With the aid of computer-assisted image subtraction the patterns of HA distribution across the tissue section were objectively identified. Anterior, posterior and presumptive soft palatal shelf regions were examined at gestational days 13.25, 13.5, 13.75 and 14.5. Acquisition of a normal pattern of HA distribution was delayed by about 24 h, as compared to untreated specimens in all three shelf regions. The posterior and soft regions, comprising the caudal two thirds of the shelf, also showed pronounced shape change. These regions only displayed normal curvature of the nasal surface when a normal pattern of HA distribution was attained. These results suggest that, for the caudal two thirds of the palatal shelf, normal shape and the ability to remodel are linked to the molecular configuration of HA and to a specific pattern of HA distribution. PMID- 2894971 TI - Felodipine versus prazosin as an addition to a beta-blocker in the treatment of essential hypertension. The Australian Multicentre Study. AB - The efficacy and tolerability of felodipine and prazosin were compared in a double-blind randomised parallel group study of 100 patients with moderately severe essential hypertension, treated concomitantly with a beta-blocking drug. After a 2- to 8-week run in phase (beta-blocking drug plus placebo), patients with a diastolic blood pressure greater than or equal to 95mm Hg were randomly given felodipine (n = 50) or prazosin (n = 50). After an initial dose of either felodipine 2.5mg bid or prazosin 0.5mg bid for 3 days, the drugs were titrated at 2-week intervals (felodipine 5, 10, 20mg bid, prazosin 1, 2, 4mg bid) if the supine diastolic blood pressure was greater than or equal to 90mm Hg. Treatment was continued for 8 weeks. Baseline supine blood pressures of each group were similar (177/104mm Hg, felodipine; 176/103mm Hg, prazosin). At week 6, supine blood pressures in the felodipine group were 144/82mm Hg and 161/90 in the prazosin group. The reductions in systolic and diastolic blood pressures were significantly greater for the felodipine group than the prazosin group in both the supine and standing positions at all visits after baseline. At 8 weeks, supine diastolic blood pressure less than 90mm Hg was achieved in more patients in the felodipine (36/47) than in the prazosin group (20/43, p less than 0.01). The total number of adverse reactions was similar in both groups. During active therapy, a greater number of patients experienced vascular adverse reactions (oedema and flushing) with felodipine (23) than with prazosin (12). Most events were mild and did not necessitate withdrawal from therapy. There were no clinically significant changes in laboratory variables in either treatment group. Felodipine was an effective, well tolerated hypotensive agent when used concomitantly with a beta-blocking drug. In the doses used it was more effective than prazosin at reducing blood pressure. PMID- 2894972 TI - Felodipine versus hydrochlorothiazide as an addition to a beta-blocker in the treatment of hypertension. PMID- 2894973 TI - Felodipine, a new calcium antagonist, as monotherapy in mild or moderate hypertension. Cooperative study group. AB - The role of felodipine, a new calcium antagonist, as monotherapy in mild and moderate hypertension (supine diastolic blood pressure between 95 and 100mm Hg: phase V) was investigated in a placebo-controlled, double-blind study of 109 patients from 13 centres using 3 different doses. After a 2-week placebo run-in phase the patients were randomised in a double-blind fashion to receive felodipine 2.5mg bid (32 patients), 5 mg bid (30 patients), 10mg bid (24 patients) or placebo (25 patients). Clinical and laboratory measurements were performed after 1, 3 and 8 weeks. 94 patients completed the study. Felodipine reduced supine systolic blood pressure by 22mm Hg from baseline after 8 weeks' treatment on 2.5mg bid, 24mm Hg on 5mg bid and 24mm Hg on 10mg bid at 2 hours after dosage. The corresponding reduction in the placebo group was 6mm Hg. There was a reduction in supine diastolic blood pressure from baseline of 13mm Hg on felodipine 2.5mg bid, 14mm Hg on felodipine 5mg bid and 20mm Hg on felodipine 10mg bid, with no reduction in patients receiving placebo. The percentage of patients completing the study who achieved a supine diastolic blood pressure of 90mm Hg or less after 8 weeks' treatment at 2 hours after dosage was 9% on placebo, 67% on felodipine 2.5mg bid, 57% on felodipine 5mg bid and 92% on felodipine 10mg bid; and at 12 hours after dosage those achieving target supine diastolic blood pressure was 17% on placebo, 37% on felodipine 2.5mg bid, 25% on felodipine 5mg bid and 62% on felodipine 10mg bid. Felodipine was generally well tolerated, although 10 patients on felodipine 10mg bid (42%), 1 on felodipine 5mg bid (3%) and 2 on felodipine 2.5mg bid (6%) withdrew from the study because of adverse effects. One serious adverse event, a myocardial infarction, occurred during the study in a patient with a history of postprandial non-exertional chest pain. In conclusion, felodipine monotherapy appreciably reduces blood pressure in mild and moderate hypertension without significant tachycardia in the short term. Doses of felodipine 2.5mg bid and 5mg bid are better tolerated than 10mg bid and can be recommended for initial treatment in this category of patients. PMID- 2894974 TI - Felodipine in combination with a beta-blocker and a diuretic in chronic treatment of patients with refractory primary hypertension. AB - The acute antihypertensive effects of the dihydropyridine calcium antagonist, felodipine, were investigated in 12 male patients aged 43 to 64 years with uncontrolled blood pressure on combined treatment with a thiazide diuretic, a beta-blocker and hydralazine. Central and renal haemodynamics were monitored after acute oral administration (0.075 mg/kg) of felodipine in combination with the beta-blocker and diuretic. Six patients were continued on long term oral felodipine (mean dose 20 +/- 24 mg/day) in combination with the other drugs for 6 to 18 months. Ambulatory blood pressure was measured repeatedly and renal function re-examined once during long term felodipine therapy. In the 6 patients on long term therapy, systolic blood pressure was reduced from 190 +/- 17 to 149 +/- 24 mm Hg and diastolic blood pressure from 116 +/- 12 to 89 +/- 14mm Hg (p less than 0.001). No significant change in heart rate was observed (65 +/- 4 vs 62 +/- 10 beats/min). Renal plasma flow significantly increased from 284 +/- 97 to 425 +/- 131 ml/min/m2 (p less than 0.01) but glomerular filtration rate was unchanged (72 +/- 20 vs 80 +/- 22 ml/min/m2). Hence, the filtration fraction was significantly reduced and normalised in all patients (0.26 +/- 0.04 vs 0.20 +/- 0.03) [p less than 0.05]. Bodyweight was unchanged. It is concluded that felodipine is a highly potent vasodilator with a favourable effect on renal function and is suitable for long term therapy in patients with severe primary hypertension. PMID- 2894975 TI - Clinical evaluation of felodipine in hypertensive patients previously treated with a triple drug regimen. PMID- 2894976 TI - A dose-response study of felodipine in patients remaining hypertensive on a beta blocker. Canadian Felodipine Study Group. PMID- 2894977 TI - Pharmacokinetics and haemodynamics of felodipine in hypertensive patients treated concomitantly with a beta-blocker. PMID- 2894978 TI - The effects of felodipine on left ventricular function in beta-blocked patients. AB - Felodipine is a dihydropyridine calcium antagonist which has a positive inotropic effect in the dog in vivo. However to date, no inotropic effects have been described in man. Thus, the solvent for the intravenous administration of the drug was infused, followed by the active solution, in 9 beta-blocked patients undergoing coronary angiography; heart rate was held constant by atrial pacing. Haemodynamic variables were measured with the Mills combined left ventricular catheter-tip manometer and aortic electromagnetic blood velocity transducer. In all patients, peripheral vasodilatation was observed. In 8 patients, this was accompanied by a 9 to 50% increase in maximum rate of rise of left ventricular pressure indicating a small positive inotropic effect. PMID- 2894979 TI - Hormonal and blood pressure responses to tilting in beta-blocked essential hypertension treated with felodipine or prazosin. AB - A study was carried out of 22 patients with essential hypertension who were treated with metoprolol (100 mg/day) and placebo for 4 weeks. Felodipine (n = 11) or prazosin (n = 11) were then added in increasing doses (felodipine 5, 10, 20 mg bid; prazosin 1, 2, 4 mg bid) for 2 weeks until a diastolic blood pressure of less than or equal to 90 mm Hg was achieved. Acute haemodynamic and hormonal responses to 80 degrees tilting (measurements after 4 minutes' tilt) were obtained immediately prior to randomisation to felodipine or prazosin, and after 6 to 8 weeks of treatment. At randomisation, 80 degrees tilt produced no change in blood pressure and only a small increase in pulse rate. There was no significant change in the plasma renin-angiotensin system, vasopressin or adrenaline concentrations. Plasma noradrenaline concentration rose in response to 80 degrees tilt. Following substitution of felodipine (n = 11) or prazosin (n = 11) for placebo, and continuation of metoprolol, blood pressure fell. 80 degrees tilt caused no change in the plasma renin-angiotensin system, vasopressin or adrenaline concentration. Plasma noradrenaline concentration rose in response to tilt, as before. Felodipine is an effective antihypertensive agent when used with metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2894980 TI - Felodipine in hypertensive patients. A dose finding study in patients refractory to beta-blocker monotherapy. AB - In a double-blind study, 128 patients with essential hypertension, refractory to beta-blocker monotherapy, were randomised to 1 of 4 treatment groups. Felodipine 2.5 mg twice daily, 5mg twice daily, 10mg twice daily or matched placebo twice daily were administered in addition to the beta-blocker for 4 weeks. Mean supine blood pressure before randomisation to treatment was 167/104 +/- 20/7mm Hg. After 4 weeks of treatment, supine blood pressures 2 hours after dose were 161/98 +/- 20/10mm Hg (P), 152/92 +/- 23/8mm Hg (felodipine 2.5mg), 142/87 +/- 18/7mm Hg (felodipine 5mg) and 142/86 +/- 17/7mm Hg (felodipine 10mg). The falls in systolic and diastolic blood pressures were significantly greater for all 3 felodipine groups than for placebo. Blood pressure reductions were less marked 14 hours after dosage: 161/100 +/- 20/9mm Hg (P), 160/97 +/- 24/9mm Hg (felodipine 2.5mg), 153/97 +/- 21/11mm Hg (felodipine 5mg), and 157/94 +/- 19/9mm Hg (felodipine 10mg); but the two higher doses of felodipine produced a significantly greater sustained fall in blood pressure than placebo. There was a correlation between the dose of felodipine and its antihypertensive effect. Standing blood pressures were reduced to the same extent as supine measurements. Heart rate was not significantly affected. Bodyweight did not increase during the study. Side effects of felodipine therapy were minor, and mostly attributable to the vasodilatory properties of the drug. Only 4 patients withdrew because of side effects. It is concluded that felodipine is an effective and well tolerated antihypertensive drug, and that 5mg twice daily is a suitable starting dose in hypertensive patients refractory to beta-blocker monotherapy. It may be necessary to increase this dose to 10mg twice daily in selected patients. PMID- 2894982 TI - Myocardial salvage: pharmacologic treatment. AB - We have attempted to review the role of pharmacologic agents in the treatment of patients with acute myocardial infarction for the purposes of limiting infarct size. At this time, the beta-blocking agents and nitroglycerin have been the most extensively studied in clinical trials and should be part of our overall pharmacologic approach to patients with acute myocardial infarction. Treatment, however, needs to be individualized, depending on the resources available within one's hospital and community. The early treatment of patients with acute myocardial infarction is undergoing a revolution. Whereas a decade ago we were satisfied with simply monitoring patients for malignant arrhythmias, now we are aggressively attempting to limit infarct size and reperfuse myocardium. In all these proposed treatments for myocardial salvage, time is a crucial element. Therefore, emergency physicians and paramedics become a vital link to begin appropriate treatment leading to myocardial salvage and reperfusion. We must begin to think of all patients with symptoms of acute myocardial infarction as candidates for aggressive attempts at myocardial salvage. These attempts will only take place with well-coordinated, multidiscipline efforts involving cardiologists, cardiothoracic surgeons, emergency physicians, paramedics, and critical care teams. Our challenge over the next few years will be to develop efficient systems so that all patients with acute myocardial infarction can receive optimal care. PMID- 2894981 TI - Update on antiarrhythmic drugs in emergency medicine. AB - Most patients presenting to the Emergency Department with acute arrhythmias can be adequately treated with the available, conventional antiarrhythmics. Recent studies have taught us to use them with better understanding. In the future, several new antiarrhythmics look promising for use in the Emergency Department when given by the intravenous route; particularly, pirmenol, encainide, esmolol, amiodarone, sotalol, and magnesium. However, there have been few comparison studies between various antiarrhythmics, and experience must be gained for a full understanding of the benefits and risks of these agents. PMID- 2894984 TI - Molecular pathology of scrapie-associated fibril protein (PrP) in mouse brain affected by the ME7 strain of scrapie. AB - Scrapie-associated fibrils (SAF) are disease-specific structures found in extracts of the brains of animals affected with scrapie. These structures are pathological aggregates of a normal host protein (PrP). Abnormal post translational modification of PrP has been suggested to explain its aberrant properties in scrapie-affected brains and although there is a form of PrP in SAF indistinguishable in size from the protein in uninfected brain, lower-molecular mass variants of PrP are also found in SAF fractions. We report the characterisation of the multiple forms of PrP found in SAF fractions purified from mouse brain affected by the ME7 strain of scrapie. The quantitatively major forms of PrP in SAF prepared without the use of proteinase K have the amino terminal sequence Lys-Lys-Arg-Pro-Lys-Pro-Gly-Gly-, identical to that predicted for the amino-terminus of normal mouse brain PrP. However N-terminal cleavage of some PrP does occur in vivo within a domain of repetitive sequences at sites similar to but distinct from those cut by proteinase K in vitro. This suggests the conformation of the protein in aggregates in vivo does not differ extensively from that in detergent-treated SAF in vitro. We conclude that the size diversity of PrP in SAF is only partly due to N-terminal proteolysis and is independent of the proteolysis that occurs if proteinase K is used in the purification of SAF. Apart from proteolytic changes in the structure of PrP, we found a novel, as yet unidentified, amino-acid derivative of the arginine residue at position 3 in mouse PrP, which may predispose PrP to form SAF. PMID- 2894985 TI - Atrial natriuretic peptide induces breakdown of phosphatidylinositol phosphates in cultured vascular smooth-muscle cells. AB - Discrepancies exist between extent of guanylate cyclase activation by atrial natriuretic peptide (ANP) in cell-free systems and ANP-stimulated levels of cyclic GMP in whole cells, and also between receptor affinity and dose effectiveness of ANP. Therefore, we have investigated whether, in addition to receptor-coupled guanylate cyclase activation, other second-messenger cascade systems may be involved in mediating both an increase in cyclic GMP and the physiological response to ANP. Equilibrium 125I-ANP binding studies on cultured thoracic aorta smooth muscle cells revealed the existence of low-affinity (approximately 10(-8) M, 84.5 fmol/10(5) cells) and high-affinity (approximately 10(-10) M, 12.5 fmol/10(5) cells) binding sites. We confirm that ANP elevates intracellular cyclic GMP (EC50 approximately 10(-8) M) and inhibits agonist (isoproterenol and forskolin)-induced increases in intracellular cyclic AMP (IC50 approximately 10(-9) M). ANP also stimulated breakdown of phosphatidylinositol phosphates and generation of inositol phosphates with a half-maximally effective concentration of approximately 10(-10) M. The extent of phosphatidylinositol polyphosphate hydrolysis was small (120%) in comparison to that of phosphatidylinositol (Ptd-Ins) (200%). Ptd-Ins hydrolysis was paralleled by the appearance of glycerophosphoinositol, and there was also a close temporal relationship between these processes and the accumulation of intracellular cyclic GMP. Smooth muscle cells released [3H]arachidonic acid label in response to ANP (EC50 approximately 10(-10) M). Taken together, the data suggest that the vasorelaxant hormone ANP has stimulatory effects on phosphoinositol lipid metabolism via both phospholipase C (generation of inositol phosphates) and phospholipase A2 (generation of releasable [3H]arachidonic acid and indirectly glycerophosphoinositol). In contrast, stimulation of phosphatidylinositol phosphate breakdown by the vasoconstrictive hormone angiotensin II is not associated with glycerophosphoinositol formation, and neither cyclic GMP nor cyclic AMP levels were influenced by this hormone. PMID- 2894983 TI - A Xenopus laevis gene encodes both homeobox-containing and homeobox-less transcripts. AB - A cDNA clone (p52) that contains all the protein-coding region from the maternally expressed XlHbox 2 locus of the frog Xenopus laevis has been isolated and sequenced. A probe containing the exon preceding the homeobox detected transcripts which arise from a splicing event in which the homeobox-containing exon is replaced by another exon lying 5' to it in the genome. Both the homeobox containing and homeobox-less splicing event occur in the same tissues, with the homeobox-less RNA representing the minority of mRNA from this gene. There may therefore be a function for two types of transcript, and hence protein, from this locus. This phenomenon may not be exclusive to the XlHbox 2 gene of Xenopus, but might occur more generally in other homeobox-containing genes. The protein deduced from the homeobox-containing cDNA is significantly similar to the yeast mating type factor a1 (MAT-a1) gene product. In addition to the previously described homology of the homeodomains, the amino-terminal domains of XlHbox 2 and MAT-a1 are similar to each other; thus essentially all of the MAT-a1 protein corresponds to some part of the XlHbox 2 protein. In the case of XlHbox 2, the protein coded for by the homeoboxless mRNA would contain all of the non-homeobox homology to yeast MAT-a1. PMID- 2894986 TI - Identification of [1-14C]pantothenic-acid-mediated modified mitochondrial proteins. AB - The in vivo administration of [1-14C]pantothenic acid, which is the precursor of coenzyme A, resulted in the radioactive labelling of several mitochondrial proteins in rat liver. The incorporated radioactivity could be released by glutathione or 2-mercaptoethanol. Two mitochondrial matrix proteins acetyl-CoA acetyltransferase (liver and heart), an enzyme involved in the biosynthesis or degradation of ketone bodies, and 3-oxoacyl-CoA thiolase (liver), a protein participating in fatty acid oxidation were identified as modified proteins. The radioactivity was localized exclusively in forms A1 and A2 indicating that these forms represent the modified states of the acetyl-CoA acetyltransferase protein. Kinetics of incorporation of radioactivity revealed an accumulation of the modified forms. The ratio of specific radioactivities of A2 compared to A1 was 2.41 +/- 0.15 (n = 10). After in vivo labelling with [14C]leucine, the specific radioactivity of acetyl-CoA acetyltransferase depended on the state of the enzyme protein. The unmodified enzyme exhibited a lower specific radioactivity than its modified forms suggesting different turnover rates of these proteins. PMID- 2894987 TI - NH2-terminal sequence of the isolated yeast ATP synthase subunit 6 reveals post translational cleavage. AB - The three mitochondrially translated ATP synthase subunits of Saccharomyces cerevisiae were extracted from the enzyme and from whole mitochondria using an organic solvent mixture and then purified by reverse-phase HPLC. The amino acid composition of subunit 6 is close to the one predicted from the oli2 gene. The partial amino terminal sequence of subunit 6 reveals a post-translational cleavage site between the Thr-10 and Ser-11 residues of the precursor. Thus, mature subunit 6 contains 249 amino acid residues and displays a molecular mass of 27943 Da. PMID- 2894988 TI - Coated pits in interphase and mitotic A431 cells. AB - Endocytosis is inhibited during mitosis in A431 cells (Warren et al., 1984) but the site of inhibition is unknown. A quantitative method measuring the extent of budding was used to compare coated pits in interphase and mitotic cells. Every stage of budding found in interphase cells was also found in cells at every stage of mitosis. Flatter coated pits appeared more frequent in mitotic cells but this can be partly, if not entirely, explained by their greater size. We conclude that, if budding is inhibited, inhibition must occur at all stages of the budding process. PMID- 2894989 TI - The effect of exercise on myocardial perfusion and function in patients with coronary heart disease. PMID- 2894990 TI - Potential time saving with pre-hospital intervention in acute myocardial infarction. Report of the European Myocardial Infarction Project (E.M.I.P) Sub Committee. AB - The European Myocardial Infarction Project (E.M.I.P.) participants have evaluated out-of-hospital coronary care services in different cities within the E.E.C. and concluded that these facilities would support a study within these European centres on pre-hospital intervention in myocardial infarction. Based on a pilot study of 2443 patients with suspected myocardial infarction, simple criteria based on chest pain and first ECG finding have been defined to allow selection of out-of-hospital patients for a trial of pre-hospital drug evaluation. Pre hospital treatment should reduce delay to intervention by about 1 h. PMID- 2894991 TI - Trials in coronary heart disease and hypertension with special reference to the elderly. AB - The risks of complications like death, myocardial infarction and stroke increase continuously with increasing age. Therefore, the chances of detecting effects of treatment in trials also increase when patients get older. The relationships between different end-points change with age, e.g. the ratio between stroke and MI increases with age. However, interventions not related to the interventions under study may also increase, causing dilution of effects. The older subject may also be more vulnerable to the side-effects of treatment. Side-effects, and quality-of-life measures, which indeed may vary with age, must be properly balanced against effects on 'hard' end-points. A review of trials in patients with hypertension and myocardial infarction shows that effects of various interventions have been at least as great in older as in younger patients. However, metabolic side effects such as impaired glucose metabolism, increased serum creatinine, and increased uric acid levels have not been negligible, and such effects may turn out to be more hazardous in the elderly than in younger patients. The balance between positive and negative effects must be properly assessed in relation to the prognosis of the untreated condition. Patients who have suffered a myocardial infarction have, in general, a more serious prognosis than most hypertensives, and more side-effects of treatment may therefore be accepted in patients with myocardial infarction. PMID- 2894992 TI - The epidemic of AIDS virus infection, what is the interest for oncologists? PMID- 2894993 TI - Antihistamine activity and central effects of WAL 801 CL in man. AB - The tolerability and antihistaminic activity of WAL801 CL, a new, peripherally acting H1-receptor antagonist, have been evaluated in a double-blind, placebo controlled, within-subject cross-over study. WAL801 CL 8 mg b.d. was given to 10 healthy volunteers for 15 days. It resulted in a distinct reduction in histamine wheal size and a decreased bronchoconstrictor response to histamine inhalation. No cardiovascular side effects were observed. Transient and slight fatigue was observed in 3 subjects. Psychological tests, such as simple visual reaction time, critical flicker fusion frequency and mood self rating scale, showed that WAL801 CL had no sedative side effects and that it did not alter psychomotor performance. PMID- 2894995 TI - CD4-/CD8-T cells: amplification in spleens of mice following in vivo treatment with monoclonal antibody anti-L3T4. AB - Amplification of L3T4-/Ly-2-(CD 4-/CD 8-) T cells following in vivo administration of anti-L3T4 monoclonal antibody was examined in the spleen of mice by flow cytometry and immunohistochemistry. BALB/c mice were given 4-7 weekly injections of either anti-L3T4 (1 mg/week) or phosphate-buffered saline (control group), and dispersed spleen cells and tissue sections analyzed for the presence of Thy-1.2+, L3T4+, or Ly-2+ cells, and for the absence of both L3T4 and Ly-2 on Thy-1.2+ cells. Prior to treatment, L3T4+ and Ly-2+ cells accounted for virtually all Thy-1.2+ cells in approximately a 2:1 ratio. Following anti-L3T4 treatment, L3T4+ cells were depleted, and Ly-2+ cells accounted for about 2/3 of the Thy-1.2+ cells. A population of L3T4-/Ly-2- T cells was generated that accounted for 20-30% of the Thy-1.2+ cells, accounted for most of the Thy-1.2+ cells in red pulp, and was also present among the predominant Ly-2+ cells in periarteriolar sheaths. PMID- 2894994 TI - The influence of beta-adrenoceptor antagonists with and without partial agonist activity on exercise tolerance and muscle lactate production. AB - Epanolol is a beta-adrenoceptor antagonist with partial agonist activity, a property which could be useful in reducing the fatigue associated with beta blockers. In a double-blind, randomized, crossover study we have investigated the effects of metoprolol 100 mg b.d., epanolol 100 mg b.d., and epanolol 200 mg b.d. on blood pressure, heart rate, and exercise-induced fatigue in 10 hypertensive men. Fatigue was measured subjectively by the Borg rating scale and objectively by blood lactate concentrations. Resting and exercise heart rates were lower with metoprolol than with either dose of epanolol. Preexercise standing diastolic blood pressure was lowered by metoprolol, but there were no other treatment effects on blood pressure. Exercise-induced fatigue was not altered by any treatment, whether measured subjectively or objectively. These results do not support the hypothesis that partial agonist activity improves exercise tolerance in hypertensive patients treated with beta-adrenoceptor antagonists. PMID- 2894996 TI - Subpopulations of CD4- CD8- murine thymocytes: differences in proliferation rate in vivo and proliferative responses in vitro. AB - Cell sorting and cytotoxic depletion procedures were used to subdivide the population of CD4- CD8- ("double-negative") thymocytes from adult CBA mice on the basis of expression of Ly-1, HSA (the "heat-stable antigen" M1/69 or B2A2), Pgp-1 glycoprotein, Thy-1, MEL-14 and the PC61 antigenic determinant on the IL2 receptor (IL2R). The level of dividing cells within these subsets was assessed by brief in vivo administration of [3H]-thymidine, followed by radioautography, or by flow cytometric cell cycle analysis after DNA staining. The capacity of the subsets to proliferate in culture, in response to stimulation with concanavalin A (Con A), or with phorbol myristate acetate (PMA) and the calcium ionophore ionomycin, was assessed in high cloning efficiency single-cell culture systems. In general, the proliferative response in culture was inversely related to the rate of cell division in vivo. Response of the double-negative subsets to Con A correlated with expression of the T cell antigen receptor complex; although a high cloning efficiency was obtained from the receptor-positive fractions, very few of the clones were cytotoxic. In particular, a major Ly-1+ HSA- Pgp-1+ double negative subset, as well as minor Ly-1- HSA- Pgp-1+ subsets, contained very few cells in cycle in vivo, but showed a high cloning efficiency in both culture systems. Conversely, the other major double-negative subset, Ly-1- HSA+ Pgp-1-, included most of the cells in cycle, but showed a reduced cloning efficiency in response to PMA and ionomycin and failed to respond to Con A. The dividing cells within the Ly-1- HSA+ Pgp-1- group were strongly enriched in the IL2R- rather than in the IL2R+ subset, suggesting IL2 was not the growth factor maintaining their proliferation in vivo. PMID- 2894997 TI - Analysis of the tachycardiac response to 5-hydroxytryptamine in the spinal guinea pig. AB - The mechanism of the increase in heart rate caused by 5-hydroxytryptamine (5-HT) in the spinal guinea-pig was investigated. Administration of 5-HT (15, 30, 60 and 120 micrograms.kg-1 i.v.) elicited dose dependent increases in heart rate. The responses to 5-HT were not modified by methiothepin (0.5 and 1.5 mg.kg-1), ketanserin (0.5-4.5 mg.kg-1) or MDL 72222 (0.5-4.5 mg.kg-1) but were antagonized by the beta-adrenoceptor antagonists, propranolol (0.1-1 mg.kg-1) or atenolol (0.5-4.5 mg.kg-1). Indalpine, which is known to interfere with the uptake of 5-HT by nerve terminals and blood platelets, significantly reduced the effects of 5-HT at a dose (5 mg.kg-1) that also affected the tachycardia elicited by tyramine. The increase in heart rate caused by tyramine in reserpinized animals was attenuated and, unlike normal animals where the responses to 5-HT remained constant after repeated administration, there was a quickly developing tachyphylaxis to 5-HT. These results show that the increase in heart rate elicited by 5-HT in spinal guinea-pigs is not mediated by any of the currently characterized 5-HT receptors ('5-HT1-like', 5-HT2 and 5-HT3), and that a major part of the tachycardia seems to be mediated by a release of catecholamines by a mechanism similar, though perhaps not identical, to that for tyramine. Another as yet unidentified mechanism could be involved besides though perhaps not identical, to that for tyramine. Another as yet unidentified mechanism could be involved besides this action. PMID- 2894998 TI - Can benzodiazepines be classified by characterising their anticonvulsant tolerance-inducing potential? AB - The development of anticonvulsant tolerance with three benzodiazepines was assessed in mice using a slow intravenous infusion of pentylenetetrazol as the convulsive stimulus. Chlordiazepoxide (12.5 mg/kg b.d.) and midazolam (0.75 mg/kg b.d.) induced a slowly evolving tolerance over 15 days whereas nitrazepam (0.6 mg/kg b.d.) induced a very marked rapid tolerance which developed no further during 6 days treatment. Tolerance appeared to be incomplete with all three benzodiazepines. Possible explanations for the differences in tolerance profile are discussed and an alternative basis for the classification of benzodiazepines is suggested. PMID- 2894999 TI - The pharmacological selectivity of three NMDA antagonists. AB - Three N-methyl-D-aspartate (NMDA) antagonists (+/-)2-amino-5-phosphonopentanoate (AP5), 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and ((+/-) 5-methyl-10,11-dihydro-5H-dibenzo(a.d.)cyclohepten-5,10- imin e maleate) (MK-801) have been tested for selectivity against depolarization of motoneurones induced by carbachol, 5-hydroxytryptamine, noradrenaline and substance P in isolated immature rat spinal cord preparations. AP5 (400 microM) and CPP (50 microM) gave mean dose-ratios, for antagonism against NMDA, of 103 +/- 14.9 S.E.M. (eight preparations) and 34.1 +/- 1.9 S.E.M. (14 preparations). MK-801 (1 and 10 microM) was the most potent of the three antagonists yielding dose ratios greater than 100 after 120 min treatment. MK-801 potentiated responses induced by 5 hydroxytryptamine and noradrenaline given dose-ratios of 0.22 +/- 0.16 S.E.M. and 0.20 +/- 0.06 S.E.M., respectively (four preparations). The three antagonists produced no significant antagonism of the non-amino acid agonists (four preparations for each agonist) when dose-ratios against NMDA were at least 40. The observations support the use of these antagonists as tools to identify sites of excitatory amino acid-mediated transmission. PMID- 2895000 TI - The mode of vasoinhibitory action of a pyridazione derivative (MCI-154), a new cardiotonic agent, on contractile responses induced by alpha-adrenoceptor agonists and 45Ca influx in isolated vascular smooth muscles. AB - The vasoinhibitory effects of MCI-154 (MCI), a new pyridazione derivative, on contractile responses to alpha 1- and alpha 2-adrenoceptor agonists were examined in isolated rabbit aorta. MCI (10(-8)-10(-5) M) inhibited the maximum contractile responses to clonidine and BHT-920 (BHT) in a concentration-dependent manner, but only inhibited responses to lower concentrations of methoxamine. In aortas pretreated with phenoxybenzamine however, MCI (10(-5) M) readily inhibited responses to methoxamine. MCI (10(-5) M) had no significant effect on responses to potassium or added Ca2+ in a Ca2+ free, K+-depolarizing medium. In aortas incubated in a Ca2+-free medium with EGTA, the addition of methoxamine (10(-5) M), clonidine (10(-5) M) or BHT (3 X 10(-4) M) induced a phasic contraction. The inhibitory effect of MCI (10(-9)-10(-5) M) on these phasic responses was much greater for clonidine or BHT than for methoxamine. In rabbit iliac artery caffeine (10 mM) induced a rapid phasic contraction in a Ca2+-free medium, which was inhibited by MCI (10(-7)-10(-5) M) in a concentration-dependent manner. In aortas incubated in a Ca2+-free medium with low EGTA and nifedipine (10(-6) M) in the presence of alpha-adrenoceptor agonists (methoxamine, clonidine or BHT), the addition of Ca2+ (2 mM) induced a tonic contraction. MCI (10(-8)-10(-5) M) inhibited these Ca2+-dependent, agonists-mediated responses in a concentration dependent manner. MCI had no effect on unstimulated La3+ resistant Ca2+ binding or methoxamine-induced Ca2+ influx.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2895001 TI - Characterization of dopamine-induced potassium efflux in rat parotid acinar cells. AB - The effects of dopamine and noradrenaline on potassium efflux from rat parotid gland were studied in a perifusion system. Tissue specimens were preincubated with 86RbCl and the efflux of 86Rb+ was used as a marker for potassium efflux. Noradrenaline induced 86Rb+ efflux more effectively than dopamine. The noradrenaline-induced efflux was inhibited by alpha-adrenoceptor blockers, especially the alpha 1-antagonist prazosin. The dopamine-induced 86Rb+ efflux was blocked by alpha-adrenoceptor antagonists, non-selective dopamine antagonists and a D-1 selective dopamine antagonist. The D-2 selective drug, sulpiride, did not affect the dopamine-induced 86Rb+ efflux. The dopamine effect was abolished when reserpinized animals were used, whereas the effect of noradrenaline was unaffected. The results suggest that dopamine has a presynaptic stimulatory effect in rat parotid gland, and that the presynaptic effect on potassium efflux seems to be mediated via the D-1 receptor subtype. Whether activation of the presynaptic D-1 receptors leads to noradrenaline release, or whether the D-1 receptor is coupled to the catecholamine transporter system remains to be studied further. PMID- 2895002 TI - Possible role of excitatory amino acids in the convulsant action of catechol. AB - The effects of several excitatory amino acid receptor antagonists on sensory evoked electromyographic activity induced by catechol have been studied in urethane-anaesthetised rats. 2-Amino-5-phosphono-valearic acid (1.2 mumol/kg i.c.), cis-2,3-piperidine dicarboxylic acid (1.4 mumol/kg i.c.), gamma-D-glutamyl glycine (2.0 mumol/kg i.c.), 2-amino-7-phosphono-heptanoic acid (230 mumol/kg i.v.) and MK-801 (5 mg/kg i.p.) all significantly decreased the frequency of occurrence of those components of the sensory evoked EMG dependent on supraspinal structures, but were without effect on the spinal component. PMID- 2895003 TI - Dynorphin A-(1-13) attenuates withdrawal in morphine-dependent rats: effect of route of administration. AB - Rats were made tolerant to morphine by subcutaneous implantation of morphine alkaloid pellets. Three days after pellet implantation, withdrawal was induced by pellet removal and was assessed 6 h later. Immediately prior to withdrawal assessment, rats were injected with dynorphin A-(1-13) either i.th. (via a catheter), i.c.v. (via a cannula) or i.v. (via the tail vein). When administered i.th. in the dose range 1.25-5 nmol/rat, dynorphin A-(1-13) attenuated withdrawal over the 40 min observation period. Similarly, dynorphin A-(1-13) administered i.v. (37.5-150 nmol/kg) attenuated withdrawal, though only over the first 20 min following administration. Dynorphin A-(1-13) up to 10 nmol/rat had no effect on withdrawal scores. These data indicate that dynorphin acts at spinal sites to suppress withdrawal in morphine-dependent rats and may play a role in tolerance and dependence mechanisms. PMID- 2895004 TI - Age-related differential recovery rates of rat striatal D-1 dopamine receptors following irreversible inactivation. AB - We report here the effects of age on the steady state levels of [3H]flupentixol labeled striatal D-1 dopamine receptors and their recovery rates following irreversible blockade in mature (4 months old) and senescent (28 months old) male Fischer 344 rats. Senescent rats exhibited significantly reduced (-22%) Bmax levels of D-1 dopamine receptors compared with their mature counterparts. In addition, the time course of recovery of D-1 dopamine receptors following irreversible receptor inactivation by a single injection of N-ethoxycarbonyl-2 ethoxy-1,2-dihydroquinoline (EEDQ) was significantly slower in senescent animals. This slower recovery rate was the result of decreases in both receptor production rate and receptor degradation rate constants compared with mature rats. Although EEDQ irreversibly inactivated D-1 dopamine receptors, it was without effect on dopamine uptake sites. A chronic, 21 day reserpine treatment did not significantly alter the Bmax nor the rate of recovery of D-1 dopamine receptors with respect to values in age-matched non-reserpine-treated rats. These data indicate that both the steady state levels of striatal D-1 dopamine receptors and the 'turnover' of these receptors are significantly affected as a consequence of natural aging. PMID- 2895005 TI - Differential effect of pertussis toxin on pre- and postjunctional alpha 2 adrenoceptors in the cardiovascular system of the pithed rat. AB - The role of the pertussis toxin-sensitive guanine nucleotide binding regulatory protein in pre- and postjunctional alpha 2-adrenoceptor-mediated responses has been investigated in the pithed rat. Pertussis toxin (50 micrograms/kg i.v., administered 3 days prior to experimentation) markedly inhibited the alpha 2 adrenoceptor-mediated vasopressor response to B-HT 933, but had no effect on the alpha 2-adrenoceptor-mediated cardiac neuroinhibitory effect of B-HT 933. Thus, postjunctional alpha 2-adrenoceptor activation in vascular smooth muscle, but not prejunctional alpha 2-adrenoceptor activation on sympathetic neurons, utilizes a pertussis toxin-sensitive guanine nucleotide binding regulatory protein. PMID- 2895007 TI - The effects of ageing on vascular alpha-adrenoceptors in pithed rat and rat aorta. AB - In the pithed rat preparation in the absence of captopril, the pressor potency of the alpha 2-adrenoceptor agonist xylazine was significantly reduced in 24 month old rats. This difference between young (3-6 month) and old rats in xylazine potency was eliminated by captopril (5 mg kg-1), which caused a greater shift in xylazine potency in young than in old rats. In the rat isolated aorta, the contractile potency both of the alpha 1-adrenoceptor agonist phenylephrine and of 5-hydroxytryptamine were significantly reduced in 24 month old rats. Hence, both in pithed rats and in the rat isolated aorta, the contractile potency of alpha adrenoceptor agonists is reduced in aged rats, but the altered responsiveness is not at the level of the alpha-adrenoceptor. In the pithed rat, alpha 2 adrenoceptor responsiveness is reduced with ageing probably due to decreased levels of angiotensin II, and in the rat aorta alpha 1-adrenoceptor responsiveness is reduced with ageing, but since responsiveness to 5-HT is also reduced, this may be a post-receptor change in responsiveness. PMID- 2895008 TI - Comparison of the pharmacological characteristics of [3H]raclopride and [3H]SCH 23390 binding to dopamine receptors in vivo in mouse brain. AB - In vivo binding of the benzamide derivative [3H]raclopride was studied in mouse brain. The binding was saturable, reversible and stereospecific. Non-specific binding was 5-15% of the total binding. Pharmacological characterization of the binding indicated labelling of dopamine D2 receptors since the binding was potently inhibited by compounds with high affinity for this receptor in vitro. On the other hand, compounds with low affinity in vitro i.e., dopamine D1-selective compounds were weak or inactive as inhibitors of [3H]raclopride binding. A comparison of the pharmacological characteristics of [3H]raclopride and [3H]SCH 23390 binding in vivo indicated that compounds with selectivity in vitro retained this selectivity in vivo. Thus, spiroperidol, haloperidol, 1-sulpiride, clebopride, LY 171555 and (-)-NPA ((-)-N-propyl-norapomorphine) were D2 selective while SCH 23390, SKF 38393 and SKF 75670 were D1 selective. Clozapine, tilozepine, cis-flupentixol, chlorpromazine and butaclamol were non-selective both in vitro and in vivo. However, a few compounds changed profile in vivo compared to in vitro. Thus, fluperlapine and fluphenazine had a dual D1-D2 receptor profile in vitro but were D1- or D2-selective in vivo, respectively. Pergolide and molindone which were D2-selective in vitro both had a dual D1-D2 receptor profile in vivo. In conclusion, [3H]raclopride, in vivo, selectively labels the dopamine D2 receptor. Comparison of the pharmacological characteristics of [3H]raclopride and [3H]SCH 23390 binding in vivo supported the that the dopamine D1 receptor is an important target for a variety of neuroleptics, especially of the clozapine type. This may indicate that blockade of the dopamine D1 receptor conveys antipsychotic action. PMID- 2895006 TI - Inhibition of [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid binding by the excitotoxin beta-N-oxalyl-L-alpha,beta-diaminopropionic acid. PMID- 2895009 TI - Effects of CRL 40827 and salbutamol on exocrine pancreatic secretion in rats. AB - The effects of the drug CRL 40827 and salbutamol, a structurally related compound, on exocrine pancreatic secretion in acutely fistulized anaesthetized rats and in chronically fistulized conscious rats were studied. CRL 40827 and salbutamol (0.05-0.45 mumol/kg per min, for 2 h) increased the basal secretion of fluid and bicarbonate in anaesthetized rats. The effect of CRL 40827 (15% of the maximal effect of secretin) was suppressed by propranolol (a non-specific beta adrenoceptor antagonist), by ICI 118551 (a beta 2-antagonist) and by atenolol (a beta 1-antagonist). The effect of salbutamol (25% of the maximal effect of secretin) was suppressed by propranolol and ICI 118551 but was only slightly decreased by atenolol. The stimulant peak effects of CRL 40827 and salbutamol on volume and bicarbonate output were additive to those of 2-deoxy-glucose whereas the effect of 2-deoxy-glucose on protein output was not changed by either drug. CRL 40827 and salbutamol decreased the basal interdigestive protein output in a dose-related manner in conscious rats. CRL 40827 was 27 times less potent than salbutamol. The pancreatic outputs of fluid, bicarbonate and protein after an intragastric meal were decreased by both drugs. However, only salbutamol significantly decreased the cumulative effect of the meal on protein output compared to basal output. These results suggest that the stimulant effect of salbutamol on the pancreatic secretion of fluid and bicarbonate depends mainly on beta 2-adrenoceptors whereas that of CRL 40827 involves adrenoceptors of an as yet undefined subtype. PMID- 2895010 TI - Peripheral antagonistic action of trimebutine and kappa opioid substances on acoustic stress-induced gastric motor inhibition in dogs. AB - The effects of intracerebroventricular (i.c.v.), intravenous (i.v.) and oral (p.o.) administration of trimebutine on the gastric motor inhibition induced by acoustic stress were investigated in fasted dogs fitted with strain-gauge transducers on the antrum and proximal jejunum. Started 40-50 min after the last migrating motor complex, a 1 h acoustic stress delayed by 111% the occurrence of the next gastric migrating motor complex without affecting the jejunal motor pattern. This inhibition of gastric migrating motor complex induced by acoustic stress was abolished by previous p.o. administration of trimebutine (1 mg/kg) but not by its i.v. (0.1 mg/kg) or i.c.v. (0.01 mg/kg) injection. The trimebutine blockade of gastric motor alterations induced by acoustic stress was suppressed after previous i.v. treatment with MR 2266 (0.3 mg/kg) but was unaffected by naloxone (0.3 mg/kg). Furthermore oral administration of U-50488H (10 micrograms/kg) and ethylketocyclazocine (10 micrograms/kg) respectively abolished and reduced the acoustic stress-induced delay of the occurrence of the gastric migrating motor complex. We concluded that trimebutine is able to antagonize the gastric motor disturbances induced in dogs by acoustic stress, probably by acting selectively on peripheral kappa receptors located in the wall of the proximal gut and directly stimulated from a mucosal site. PMID- 2895011 TI - Inherited rod-cone dysplasia: abnormal distribution of cyclic GMP in visual cells of affected Irish setters. AB - Light-adapted retinas from Irish setters affected with inherited rod-cone dysplasia accumulate high concentrations of cyclic GMP in the outer plexiform layer (OPL). A 29-fold difference in OPL cGMP levels between affected and normal occurs at 19-20 days. However, the highest concentration, 550 mumol kg-1 (dry) wt, is reached at about 4 weeks of age, at which time OPL cyclic GMP is 20-fold higher than cGMP in the OPL of normal control retinas. Levels remain high in affected OPL until about 7 weeks of age; after this, the cyclic GMP level falls and the peak shifts to the outer nuclear layer (ONL). In the normal retina on the other hand, the highest cyclic GMP levels are in the outer segments (OS). The result is that cyclic GMP is highest at opposite ends of the photoreceptor neuron in normal and affected retinas during the first 7 weeks of development. These differing distributions are established as early as postnatal day 10, before signs of degeneration become evident, as determined by either ERG or morphological examination. Moreover, a 38-fold rise in cyclic GMP occurs in the ONL of affected retinas between 1 and 3 weeks of age significantly before the degeneration of nuclei begins at 4 to 5 weeks. The early differences in cyclic GMP distribution are probably not due to differences in guanylate cyclase activity since enzyme levels in normal and affected photoreceptor cells are virtually identical until about 4 weeks of age. Since cGMP has been observed to reach high levels in normal dark-adapted rabbit and frog OPL, the extraordinary OPL levels seen in affected setters may indicate the importance of cGMP in both normal synaptic function and in the disease process. PMID- 2895012 TI - Retardation of amygdala kindling by antagonism of NMD-aspartate and muscarinic cholinergic receptors: evidence for the summation of excitatory mechanisms in kindling. AB - DL-2-amino-5-phosphonovaleric acid (APV), a specific antagonist of N-methyl-D aspartate (NMDA) receptors, was administered alone and in combination with scopolamine (SCO), an antagonist of muscarinic cholinergic receptors, to different groups of rats undergoing electrical kindling of the amygdala. Both groups were significantly retarded in their rate of kindling during 15 drug sessions compared to controls, and the group receiving APV and SCO kindled significantly slower than the group receiving APV alone. These results indicate that both NMDA and muscarinic cholinergic receptors are involved in kindling of the amygdala, and implicate a mechanism involving the summation of excitatory neurotransmission in kindling of the amygdala. PMID- 2895014 TI - Alpha-adrenoceptor blocking action of hymenin, a novel marine alkaloid. AB - In the rabbit isolated aorta, hymenin (10(-6) M), a novel marine alkaloid, caused a parallel rightward shift of the dose-response curve for norepinephrine without affecting that for histamine or KCl, suggesting that hymenin is a competitive antagonist of alpha-adrenoceptors in vascular smooth muscles. PMID- 2895015 TI - Feeding induced by blockade of histamine H1-receptor in rat brain. AB - Histamine antagonists were infused into the third ventricle of the cerebrum in rats. All the H1-, but none of the H2-antagonists tested, induced initial feeding during the early portion of the light phase when histamine level was highest. No periprandial drinking was observed. Ambulation increased during feeding. The effect on feeding was attenuated when brain histamine was normally low during the early portion of the dark phase, or was decreased by alpha-fluoromethylhistidine. Hypothalamic neuronal histamine may suppress food intake through H1-receptors, and diurnal fluctuations of food intake may mirror neuronal histamine levels. PMID- 2895016 TI - Polymorphisms in mitochondrial DNA of European and Africanized honeybees (Apis mellifera). AB - This study demonstrates polymorphisms in both the length and in the restriction enzyme cleavage sites of honeybee mitochondrial DNA (mtDNA). The levels of variation are typical of those found in other metazoan species. These polymorphisms are potentially useful for the identification of Africanized bees in the western hemisphere and for study of honeybee phylogenetics. PMID- 2895013 TI - Ontogenic development of peptide hormones in the mammalian fetal pancreas. AB - The ontogeny of insulin, glucagon, PP and somatostatin in the mammalian fetal pancreas has been examined in recent years largely by immunocytochemistry and in some instances by radioimmunoassay. Complete ontogenic data are available only for the rat, human, pig and sheep. Figure 3 compares the time of appearance of the endocrine cell-types within the fetal pancreas when the periods of gestation of the four species are converted to a uniform scale. The striking ontogenic difference in the rat probably reflects the immaturity of the rodent fetus at birth compared with the human, pig and sheep. In the fetal pancreas, differences in cell number of glucagon and PP cells in the dorsal and ventral lobes become apparent from an early gestational period. Factors responsible for the functional and structural maturation of the fetal pancreatic endocrine cells and the processes involved in pancreatic organogenesis are poorly understood. Studies in these areas would have clinical implications since it may be possible in the future to employ agents for selective replication of fetal beta-cells for transplantation in patients with Type I diabetes, bearing in mind that such cells must have the capacity to respond to normal stimuli and repressors when transplanted. The presence of the other islet cell-types may be obligatory for these appropriate responses. This would require a more complete knowledge of those factors which produce the normal selectivity of the four hormonal cell types. PMID- 2895018 TI - The complex of mitochondrial F1-ATPase with the natural inhibitor protein is unable to catalyze single-site ATP hydrolysis. AB - Interaction of mitochondrial F1-ATPase with the isolated natural inhibitor protein resulting in the inhibition of multi-site ATP hydrolysis is accompanied by the loss of activity at low ATP concentrations when single-site hydrolysis should occur. Catalytic site occupancy by [14C]nucleotides in F1-ATPase during steady-state [14C]ATP hydrolysis, which is saturated in parallel with single-site catalysis, is prevented after blocking the enzyme with the inhibitor protein. PMID- 2895017 TI - The interaction of MgADP with H+ -ATPase in rat liver mitochondria. AB - The activating anions are found to induce an unexpectedly high (up to 8-fold for sulphite) increase of ATPase activity in intact rat liver mitochondria. This effect is not determined by the observed changes in Km and Ki (ADP) values. The stimulation seems to be caused by dissociation of the inactive complex of ATPase with Mg.ADP. The quantity of this complex formed in the course of ATP hydrolysis is approx. 90% of the total ATPase content in intact mitochondria. The data on toluene-permeabilized mitochondria suggest that the high content of the complex is a result of the stabilizing effect of some matrix macromolecules. PMID- 2895019 TI - Mode of binding of [3H]dibenzocycloalkenimine (MK-801) to the N-methyl-D aspartate (NMDA) receptor and its therapeutic implication. AB - Binding of the labeled anticonvulsant drug [3H]dibenzocycloalkenimine [(3H]MK-801 to the N-methyl-D-aspartate (NMDA) receptor and its dissociation from the receptor at 25 degrees C are slow processes, both of which follow first order kinetics (t1/2 approximately equal to 70 and 180 min, respectively). Both reactions are markedly accelerated by glutamate and glycine (t1/2 approximately equal to 5-8 and 4 min, respectively), which allow bimolecular association kinetics of the labeled drug with the receptors whereas equilibrium binding of [3H]MK-801 (Kd 2-4 nM) is hardly affected by glutamate and glycine. The data suggest that MK-801 acts as a steric blocker of the NMDA receptor channel. The competitive antagonist D-(-)-2-amino-5-phosphovaleric acid (AP-5) freezes the receptor in a state which precludes either binding of [3H]MK-801 to the receptor channel or its dissociation from it. These findings have therapeutic implications. PMID- 2895020 TI - The activation and inactivation of the Dunaliella salina chloroplast coupling factor 1 (CF1) in vivo and in situ. AB - Preillumination of intact cells of the eukaryotic, halotolerant, cell-wall-less green alga Dunaliella salina induces a dark ATPase activity the magnitude of which is about 3-5-fold higher than the ATPase activity observed in dark-adapted cells. The light-induced activity arises from the activation and stabilization in vivo of chloroplast coupling factor 1 (CF1). This activity, approximately 150-300 mumol ATP hydrolyzed/mg Chl per h, rapidly decays (with a half-time of about 6 min at room temperature) in intact cells but only slowly decays (with a half-time of about 45 min at room temperature) if the cells are lysed by osmotic shock immediately after illumination. The activated form of the ATPase in lysed cells is inhibited if the membranes are treated with ferri- but not ferrocyanide, suggesting that the stabilization of the activated form of CF1 is due to the reduction of the enzyme in vivo in the light. PMID- 2895021 TI - The partial purification of a factor from Dunaliella salina that causes the rapid in situ inactivation of light-activated chloroplast coupling factor 1 (CF1). AB - A factor having the expected properties of the in vivo oxidant responsible for inactivating the in vivo light-activated chloroplast coupling factor 1 (CF1) has been partially purified from cell-free extracts of Dunaliella salina. This factor is highly polar, weakly acidic, and relatively temperature stable. The ability of this factor to inactivate light-activated CF1 is prevented if it is pretreated with reductants such as dithiothreitol. The factor has virtually no effect on the ethanol-induced, Mg2+-dependent ATPase activity of the isolated CF1. PMID- 2895022 TI - A zebrafish homologue of the murine Hox-2.1 gene. AB - Homeobox-containing sequences were isolated from a genomic library of zebrafish (Brachydanio rerio). A lambda clone containing two homeobox cross-hybridizing regions was characterized. DNA sequencing of one of these regions (ZF-21) revealed that it contains a homeobox closely related to the Antennapedia class of Drosophila homeobox sequences. Moreover, the deduced amino acid sequence of the C terminal end (81 residues including the homeobox) is identical to the corresponding part of the murine Hox-2.1 protein. Similar to Hox-2.1, a ZF-21 derived transcript of 2.3 kb is present in embryos at the somite forming stages. PMID- 2895023 TI - Identification of a deletion in the LDL receptor gene. A Finnish type of mutation. AB - A cDNA probe for the low density lipoprotein (LDL) receptor gene was used to screen DNA samples from 52 unrelated Finnish patients with the heterozygous form of familial hypercholesterolemia (FH) and 51 healthy controls. Southern blot analysis using the restriction enzyme PvuII revealed an abnormal 11 kb (kilo base pair) restriction fragment in 16 (31%) of the patients but none of the controls. A more detailed restriction enzyme analysis of the DNA from patients revealed a mutation which apparently is due to an 8 kb deletion extending from intron 15 to exon 18 of the LDL receptor gene. Co-segregation of FH with the mutated gene was demonstrated in three families. These data are consistent with a 'founder gene effect' and support the assumption that recombinant DNA methods may have great impact on the diagnostics of FH in genetically homogeneous populations. PMID- 2895024 TI - Evidence against a tumour-specific EcoRI RFLP of the c-mos locus. AB - EcoRI restriction fragment length polymorphisms (RFLP) at the human c-mos locus were analysed in DNAs of normal individuals and tumour patients. Two alleles with fragment lengths of 2.6 kb (A1) and 5.6 kb (A2) respectively were detected. The allele distribution among the tumour group was similar to that of the control group. No difference was found between the allele frequencies in leucocytes and tumour tissue DNA of the same patients. PMID- 2895025 TI - [Studies on antibodies against TSH-receptors]. PMID- 2895026 TI - Hepatic hydrolysis of octanoyl-CoA and valproyl-CoA in control and valproate-fed animals. AB - 1. Medium-chain acyl-CoA hydrolase activities were determined in liver from control and valproate-fed rats and rabbits. 2. Octanoyl-CoA was readily hydrolyzed by all control liver preparations. 3. Animals that had been fed diets containing 0.5 or 1.0% (w/w) valproic acid had significantly elevated octanoyl CoA hydrolase activities. 4. The CoA ester of valproic acid, a branched-chain isomer of octanoic acid, was poorly hydrolyzed by liver preparations from both control and valproate-fed animals. 5. Livers from the valproate-fed animals contained high levels of medium-chain acyl-CoA; total CoA content was also increased. 6. The inefficiency of hepatic valproyl-CoA hydrolysis may play a role in the toxicity of valproic acid. PMID- 2895027 TI - Misregulation of homeotic gene expression in Drosophila larvae resulting from mutations at the extra sex combs locus. AB - Using monoclonal antibodies specific for their protein products, the expression of the Ubx, Antp, and Scr genes was examined in imaginal discs and central nervous systems of esc-Drosophila larvae. In esc-mutants, both the Ubx and Scr proteins are expressed at increased levels or in new locations in the leg discs. Ubx also is expressed in new locations in the posterior wing disc and in small groups of cells in the antenna disc. The Antp protein is expressed ectopically in the eye-antenna disc; however, obvious abnormal expression of Antp was not found in the thoracic imaginal discs. Particularly striking is the fact that a single disc, such as the mesothoracic leg, can show increased expression of both a more "anterior" homeotic gene (Scr) and a more "posterior" gene (Ubx). Ectopic expression of Ubx and Antp, but not of Scr, is seen in the central nervous system of mutant larvae. These results are discussed with respect to the adult esc phenotype and the differential effects of esc mutations on early and late development. PMID- 2895028 TI - Development of hypothalamic neurons in intraventricular grafts: expression of specific transmitter phenotypes. AB - The anlages of the medial-basal hypothalamus (MBH), septopreoptic area (POA), Rathke's pouch, and the parietal cortex (CC) of rats (at 12.5, 14.5 and 16.5 days of gestation) were transplanted singly or in combination into the third ventricle of adult female rats, and the development of neurons in the grafts was investigated immunohistochemically with the use of antisera to tyrosine hydroxylase (TH), somatostatin (SRIH), ACTH, methionine enkephalin-Arg6-Gly7-Leu8 (Enk-8), rat corticotropin-releasing factor (rCRF), rat hypothalamic growth hormone-releasing factor (rhGRF), and luteinizing hormone-releasing hormone (LHRH). TH and all the peptides examined except LHRH were detected in distinct neurons in MBH grafts and in cografts of MBH plus Rathke's pouch from 12.5-day old embryos. SRIH, rCRF, Enk-8, and TH were found in POA grafts from embryos of the same age. Although immunoreactive LHRH was first detected in neurons in POA grafts from 16.5-day-old embryos, it appeared in cografts of POA and MBH from 12.5-day-old embryos. The immunoreactive fibers developed in the grafts expressed the same characteristic behaviors as in intact brain; the fibers containing hormonal substances formed complexes with the vasculature like in the organum vasculosum laminae terminalis (OVLT) or in the median eminence, while the fibers containing neurotropic signals formed fiber networks surrounding other nerve cell bodies as if they synaptically associate. In CC grafts, the neurons contained TH, SRIH, rCRF, or Enk-8, and their axonal processes formed fiber networks. These findings suggest that all the hypothalamic neurons examined are committed by 12.5 days of gestation to develop maintaining transmitter phenotype and target recognition capacity. PMID- 2895029 TI - [Analysis of the effects of the hyperventilation test and their dynamics after administration of neuroleptics in epilepsy]. PMID- 2895030 TI - Serum lysyl oxidase activity in patients with various liver diseases. AB - Serum lysyl oxidase activity was examined in patients with various liver diseases. The activity of the enzyme was detected mainly in the serum fraction of the supernatant 80% saturated with (NH4)2SO4, and its molecular weight was estimated to be about 30,000 by Sephadex G-150 column filtration. Mean serum lysyl oxidase activity in 18 healthy controls was 129 +/- 50 (+/- SEM) cpm/ml and was significantly increased in patients with acute hepatitis, chronic active hepatitis, alcoholic liver disease and primary biliary cirrhosis, but not in those with chronic inactive hepatitis or liver cirrhosis. Serum lysyl oxidase activity was not correlated with the histological grade of hepatic fibrosis, but appeared to reflect active hepatic fibrogenesis in patients with liver diseases. PMID- 2895032 TI - [Choice of DNA probe for the analysis of the polymorphism of a beta-globin cluster in thalassemia patients]. PMID- 2895031 TI - Effects of somatostatin and pancreatic polypeptide on exocrine and endocrine pancreas in the rats. AB - The effects of somatostatin-14 (SS) and rat pancreatic polypeptide (rPP) on endocrine and exocrine functions of the pancreas, stimulated by 40 ng/kg cholecystokinin octapeptide during continuous infusion of 1 U/kg/h secretin, were investigated in the rat, in vivo. Protein output in the pancreatic juice and integrated insulin (IRI) secretion were inhibited, in a dose related fashion, by continuous infusion of SS, in doses of 0.5, 5 and 50 micrograms/100g/h. On the other hand, bicarbonate and volume output were not inhibited by SS. The rPP significantly inhibited not only the protein output but also the bicarbonate and volume output of the pancreatic juice in doses of 0.1 and 1 microgram/100g/h. Integrated IRI secretion was inhibited significantly by rPP, but the inhibition of IRI secretion was much greater in the portal than in the jugular vein. Plasma SS and rPP concentrations showed physiological ranges during infusion of doses of 0.5 and 0.1 microgram/100g/h of SS and rPP, respectively. Therefore, there was a marked difference between the inhibition by rPP and that by SS on the exocrine and endocrine pancreas. These observations suggest that SS and PP may play a physiological role in the pancreas and that their effects on the pancreas relate to different mechanisms. PMID- 2895033 TI - The comparative pharmacology of the behavioral syndromes induced by TRH and by 5 HT in the rat. AB - 1. The relationship of the behavioral syndromes induced by the co-transmitters thyrotropin releasing hormone (TRH) and serotonin (5-HT) has not been previously studied with drugs selective for 5-HT receptor subtypes. 2. Both the TRH analog MK-771 (in naive rats) and 5-hydroxytryptophan (in rats with 5,7 dihydroxytryptamine [DHT] lesions) evoked reciprocal forepaw tapping, Straub tail, hunching, hindlimb abduction, and shaking behavior. Sniffing and rearing were features of the MK-771 but not the 5-HT syndrome. 3. 5-HTP potentiated MK 771-induced hyperthermia. 4. MK-771 evoked two types of shaking behavior, head shakes (HS) and wet-dog shakes (WDS). Neither independently was dose-related, unlike total shaking behaviors. 5. MK-771-induced shaking behavior was pharmacologically dissociated from other MK-771-evoked behaviors. A 5-HT1A agonist (8-OH-DPAT) blocked WDS, but like putative 5-HT1B (RU 24969) and 5-HT2 (DOI) agonists and the 5-HT antagonists methysergide (non-selective), ritanserin (5-HT2 selective), and l-propranolol (5-HT1 selective), it did not block other antagonists behavioural effects of MK-771. 6. Ipsapirone, a 5-HT1A-active drug purported both as an agonist and as an antagonist, inhibited MK-771-evoked WDS, like 8-OH-DPAT, but did not induce the serotonin syndrome, unlike 8-OH-DPAT. 7. DHT-treated rats were behaviorally supersensitive to 10 mg/kg MK-771 as indicated by a significantly shortened latency of onset of WDS and greater frequency of abnormal forepaw movements. The same rats were also supersensitive to 50 mg/kg 5 HTP to a significantly greater degree. 8. These data suggest behavioral relatedness of the TRH and 5-HT syndromes, but distinctive pharmacologic features and presumed mechanisms of action. PMID- 2895034 TI - The effect of chronic diazepam and medazepam treatment on the number and affinity of muscarinic receptors in different rat brain structures. AB - 1. The effect of chronic (19-day) treatment with the benzodiazepine tranquilizers diazepam (1 mg/kg/day, i.p.) and medazepam (5 mg/kg/day, i.p.) on the binding characteristics of muscarinic receptors in four rat brain structures: cerebral cortex, striatum, hippocampus and hypothalamus were studied using [3H]l quinuclidinyl benzylate ([3H]QNB) as radioligand. 2. Diazepam and medazepam treatment caused an overall decrease in muscarinic receptor binding affinity (Kd). 3. The number (Bmax) of muscarinic receptors declined in the hippocampus and striatum and rose in the hypothalamus after both benzodiazepines. The Bmax of muscarinic receptors in the cerebral cortex was increased after diazepam treatment. 4. The changes in the binding characteristics of muscarinic receptors might be due to benzodiazepine-induced occurrence of two populations of muscarinic binding sites: P1 (high affinity, low capacity) and P2 (low affinity, high capacity). 5. The altered brain muscarinic receptor functions after chronic diazepam- or medazepam treatment suggest the role of cholinergic neurotransmission in the mechanism of action of benzodiazepines. PMID- 2895035 TI - Cryptolepine inhibits platelet aggregation in vitro and in vivo and stimulates fibrinolysis ex vivo. AB - 1. Cryptolepine--the methylquindolanol alkaloid of Cryptolepsis sanguinolenta was evaluated for its antiplatelet and fibrinolytic effects. 2. It exhibited antiplatelet effects in vitro in human, rabbit and rat PRP with EC50 values ranging between 8.1 x 10(-8) M and 1.7 x 10(-7) M for ADP, AA and thrombin. 3. In the rat, it inhibited ADP-aggregation in vivo with delayed onset and prolonged action. 4. In vitro, cryptolepine disaggregated (dose-dependently) platelets aggregated by ADP, AA and thrombin. 5. In addition, it exhibited an indirect fibrinolytic action in the rat possibly by causing the release of plasminogen activators from the vascular endothelium. PMID- 2895036 TI - Adverse sequelae with combined use of beta-blockers and epinephrine. PMID- 2895037 TI - External transport of beta-adrenergic binding sites in ischemic myocardium. AB - The properties of beta-adrenergic receptors were studied in normal and in flow restricted regions of the dog heart. Purified cardiac membrane preparations and papillary muscle preparations were isolated from control and ischemic areas and tested a) following chronic beta-receptor blockade with metipranolol or exaprolol, and b) after acute regional myocardial ischemia. A significant reduction in the sensitivity of the heart muscle preparations from compromised heart for isoprenaline resulting in a reduced affinity of beta-adrenergic receptors to exaprolol was observed. Quantitative ligand binding data showed higher numbers of (3H) dihydroalprenolol/(3H) DHA/binding sites in the membrane fraction obtained from compromised compared to control myocardium. The ratio of intra- to extracellular beta-adrenergic receptors decreased from 1.35 to 0.55 in the membrane fractions obtained from the compromised hearts. Pretreatment of experimental animals with metipranolol or propranolol attenuated the observed increase in the total number of beta-adrenergic receptor sites in myocardial membrane fractions from ischemic hearts. These data suggest preferential distribution of beta-adrenergic binding sites from intracellular to membrane fractions in flow restricted regions of the dog heart after coronary occlusion. PMID- 2895038 TI - Conserved 12-bp element downstream from mRNA polyadenylation sites. AB - Sequences downstream from the AATAAA motif in a number of cellular and viral transcription units have been compared. A 12-bp conserved element was identified in approximately half of the cases studied, and a consensus sequence TTGANNNTTTTTT was derived from a comparison of 74 such sequences. This element is located immediately (5-20 bp) downstream from the poly(A)-addition site in every case where this is known, and it is suggested that this element may be involved in the cleavage/polyadenylation reaction. This proposal is consistent with published studies on deletion mutants of downstream regions. PMID- 2895039 TI - Plotting genetic maps on a microcomputer. AB - Maps of genetic linkage and restriction enzyme cleavage sites can be quickly prepared on an IBM PC microcomputer with the commercially available program Lotus 1-2-3. Data can be entered on the keyboard or imported from other programs. The maps can be displayed on the screen or with a printer or plotter. These procedures should be useful in the research laboratory, in preparing figures for publication and in teaching. PMID- 2895040 TI - 3'-end modifications of the Streptococcus pneumoniae lytA gene: role of the carboxy terminus of the pneumococcal autolysin in the process of enzymatic activation (conversion). AB - Plasmids containing modifications at the 3' end of the lytA gene encoding the pneumococcal amidase were constructed by DNA recombinant techniques. Several deleted and fused amidases were obtained. These modified amidases were capable of degrading cell walls containing choline residues in their teichoic acid components without need of conversion (i.e., change of the inactive E form of amidase to the active C form). The reintroduction of as few as the terminal 11 amino acid (aa) residues present in the wild-type (wt) amidase into the sequence of the most extensively deleted form of the autolysin obtained in this work (E 520) partially restored the need of conversion. Our results demonstrate the importance of the C terminus for the catalytic activation of the wt amidase. PMID- 2895042 TI - Autonomic neuroeffector mechanisms: recent developments. AB - Peripheral autonomic control mechanisms are more sophisticated than formerly recognized. The autonomic neuroeffector junction is defined, with emphasis on 'en passage' release of transmitter from varicosities in extensive terminal branching nerve fibres. In addition to the classical autonomic transmitters acetylcholine and noradrenaline, a multiplicity of other neurotransmitter substances are also present, including peptides, purines, indoleamines and amino acids. There is coexistence of different combinations of these substances which, upon release, act either as cotransmitters or neuromodulators. Examples are described, including cotransmission and neuromodulation at sympathetic, parasympathetic and sensory-motor neuroeffector junctions. The involvement of locally released agents in peripheral control is also described, including substances produced secondarily as a result of release of neurotransmitters, as well as the release of substances from vascular endothelial cells leading to vasodilatation. PMID- 2895041 TI - Antihypertensive treatment and postprandial blood pressure reduction in the elderly. AB - Recently it has been demonstrated that blood pressure in the elderly decreases after a meal. To evaluate the influence of antihypertensive treatment on postprandial blood pressure reduction in the elderly, the effects of a breakfast (405 kcal) on blood pressure and heart rate were studied in 15 healthy normotensive elderly subjects (mean age 79.5 +/- 6.0 years), in 10 healthy hypertensive elderly subjects (mean age 80.2 +/- 5.7 years) and in 22 hypertensive elderly subjects (mean age 71.4 +/- 5.0 years) treated with antihypertensive medication (diuretics, beta-blockers, vasodilators). In the three groups there was a fall of mean arterial blood pressure of 9.3 +/- 1.9%, 13.8 +/- 1.9% and 7.9 +/- 1.3%, respectively, at 40 min after the start of the breakfast. In all three groups heart rate increased significantly. It is concluded that antihypertensive treatment with the regimens used in this study does not induce an additional fall of blood pressure postprandially. However, the influence of eating should be avoided in the assessment of antihypertensive drug effects in the elderly. PMID- 2895043 TI - Isolation, biochemical analysis, and N-terminal amino acid sequence of a cell surface glycoprotein that binds to the "erythrocyte receptor" of T-lymphocytes. PMID- 2895044 TI - Activation of natural killer function through the T11/E rosette receptor. PMID- 2895046 TI - Replication and pathogenesis of the human T-cell leukemia/lymphotropic retroviruses. AB - The broad outlines of mechanisms of tumorigenesis by the HTLV-I family of viruses are beginning to emerge. The viruses encode at least three genes in addition to the genes (gag, pol, and env) required for virus replication. These additional genes encoded for by the X region are likely to affect in a specific fashion the growth of lymphocytes. The tat gene appears to mimick at least part of the response of mature lymphocytes to recognition of the cognate antigen. That is, in T-lymphocytes the tatI gene seems to induce the IL-2 and IL-2 receptor genes (W. Greene et al. 1986). The alternative reading-frame proteins, pp21 and pp27, have some similarity of cellular proteins that are associated with G0 to G1 transitions and may contribute to the transformed phenotype in cooperation with the tat gene. The expression of viral genes in infected lymphocytes, the tat gene and pp21 and pp27 proteins, and possibly other viral genes (since the coding capacity of the X region is not exhausted by the tat and pp21 and pp27 proteins) may be sufficient to account for the transformation of T cells in culture. A secondary change in the infected cells in culture is not required to explain the outgrowth of cells which are clonal with respect to the site of viral genomic integration, as selection of the most rapidly growing infected cell could account for this observation. The case of infected patients is more complex. Infection of T cells with the HTLV-I or -II virus is not sufficient to produce malignant disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2895045 TI - Are haematophagous insects vectors for HTLV-I? PMID- 2895047 TI - Preleukemia and typical adult T-cell leukemia (ATL) etiologically associated with a retrovirus (HTLV/ATLV). PMID- 2895048 TI - Hematopoietic stem cells as potential vehicles for recombinant genes in prenatal mice. PMID- 2895049 TI - Genetic polymorphism of plasminogen. AB - By isoelectric focusing in a pH range of pH 3.5-9.5 or of pH 5-8, and by using a functional or an immunological detection, a genetic polymorphism of plasminogen can be demonstrated. In Caucasoids, 2 common alleles--PLGA (frequency 0.67) and PLGB (frequency 0.30)--as well as several rare variants (sum of their frequencies 0.03) exist. Systematic studies on the functional activity of the various plasminogen gene products should be performed in order to analyse whether or not a difference of plasminogen activity can be observed amongst the possible phenotypes and in order to see whether or not the various plasminogen phenotypes have any clinical significance. PMID- 2895050 TI - [Free transfer of a lateral upper arm flap]. AB - A free fascio-cutaneous flap can be raised from the lateral arm. This flap is especially suitable for smaller defects. The area is supplied by a terminal branch of the profunda brachii artery. The anatomy of the donor site as well as several steps in dissection are described. Three cases where a lateral arm flap has been used are shown, together with a rare intraoperative complication. PMID- 2895051 TI - [H1-receptor blockers: review and preview]. PMID- 2895052 TI - [Adenosine and muscarinic receptors in regulation of myocardial contractility: dual mechanism of inhibitory action]. AB - In mammalian cardiac muscle, muscarinic and adenosine receptors serve as inhibitory physiological modulators of myocardial functions. Dual inhibitory regulation of myocardial function via stimulation of these receptors is established through cyclic AMP-dependent and cyclic AMP-independent subcellular processes. The inhibitory signals triggered by agonist binding to the respective receptors are transmitted to the subsequent biochemical, electrophysiological and functional changes through activation of the GTP-binding proteins, Ni and/or N0, which couple the signal at binding sites to the catalytic subunit of adenylate cyclase in the actions mediated through the cyclic AMP-dependent mechanism, or to potassium channels in those mediated by cyclic AMP-independent processes preferentially exerted in atrial and SA nodal cells. The functional role of polyphosphoinositide breakdown promoted by muscarinic receptor activation in myocardium has not been elucidated. IAP (islet-activating protein, pertussis toxin) is capable of uncoupling the receptor stimulation to activation of Ni and/or N0, thus resulting in the inhibition of negative inotropic and chronotropic responses to muscarinic receptor agonists, and to adenosine and its derivatives such as N6-phenylisopropyladenosine and N6-methyladenosine. Both the cyclic AMP-dependent and cyclic AMP-independent inhibitory mechanisms are susceptible to IAP. PMID- 2895053 TI - [Evaluation of tiquizium bromide (HSR-902) as an antiulcer agent]. AB - The effects of HSR-902, an antimuscarinic agent, on development of various gastric and duodenal lesions, gastric secretion, pupil size and salivation in rats were compared with those of pirenzepine.2HC1 (pirenzepine, antiulcer agent) and timepidium bromide (timepidium, antispasmodic). 1) HSR-902 (10-100 mg/kg), given orally, dose-dependently inhibited the developments of gastric lesions induced by water-immersion stress, aspirin, indomethacin, serotonin and reserpine and duodenal lesions induced by cysteamine and mepirizole. The activities of HSR 902 were almost equal or somewhat more potent than those of pirenzepine, and they were more potent than those of timepidium. 2) HSR-902 (30 and 100 mg/kg, p.o.), when examined using pylorus-ligated preparations, dose-dependently inhibited the gastric acid output, pepsin output, and gastric acid and pepsin concentrations, but did not inhibit the gastric volume (HSR-902, in a higher dose, slightly increased the gastric volume.). Pirenzepine (100 mg/kg, p.o.), like atropine sulfate, inhibited the gastric volume, acid output and pepsin output, but did not inhibit the gastric acid and pepsin concentrations. Timepidium (100 mg/kg, p.o.), however, hardly influenced these parameters except for increasing the gastric volume. 3) HSR-902 (100 mg/kg, p.o.) induced the mydoriasis and inhibited the pilocarpine-induced salivation, and its activities were less potent than those of pirenzepine. These results suggest that HSR-902 is a promising agent for the treatment of peptic ulcer. PMID- 2895055 TI - Acinetobacter calcoaceticus foot infection secondary to high-pressure injection injury: a case report. AB - Injection injuries are surgical emergencies occurring most often in the hand and frequently associated with widespread tissue necrosis and infection. This report presents a case of high-pressure injection injury of the foot associated with extensor hallucis longus laceration and infection with Acinetobacter calcoaceticus variant anitratus. This injury occurred with a high-pressure "water blaster" tool used to remove paint from pavement. Similar injuries in the foot have not been reported. A. calcoaceticus is a widely distributed normal flora of low virulence, often waterborne, which is rarely found in orthopaedic infections in young healthy patients. Clinical features of high-pressure injection injuries, principles of treatment, and the characteristics of A. calcoaceticus are reviewed. PMID- 2895054 TI - [Cytoprotective activity of tiquizium bromide (HSR-902) and its mechanism]. AB - The effects of HSR-902, an antimuscarinic agent, on acute gastric mucosal lesions induced by various necrotizing agents, gastric mucus secretion and gastric HCO3- secretion in rats were compared with those of pirenzepine.2HCl (pirenzepine), an antiulcer agent. 1) HSR-902 (10-100 mg/kg), given orally, dose-dependently prevented the gastric mucosal lesions induced by ethanol-HCl (60% ethanol in 150 mM HCl), aspirin-HCl (150 mg/kg of aspirin in 150 mM HCl), 0.6 N HCl and 0.2 N NaOH; and the cytoprotective effects of HSR-902 were almost equal or somewhat more potent than those of pirenzepine. 2) HSR-902 (30 mg/kg, p.o.), like pirenzepine, increased the alcian blue binding to gastric mucosa and both hexosamine and N-acetylneuramic acid in gastric juice and reversed the decrease of alcian blue binding to gastric mucosa in water-immersion stress. 3) HSR-902 (30 mg/kg, p.o.), unlike pirenzepine and atropine sulfate, increased the gastric HCO3- secretion in the pylorus-ligated preparations. 4) The cytoprotective effect of HSR-902 (30 mg/kg, p.o.), when examined using gastric mucosal lesion induced by aspirin-HCl, was not abolished by the pretreatment with indomethacin (10 mg/kg, s.c.) or N-ethylmaleimide (10 mg/kg, s.c.). 5) HSR-902 (30 mg/kg, p.o.) did not influence the gastric mucosal potential difference. These results suggest that HSR-902 is a promising drug for the treatment of gastritis and peptic ulcers. PMID- 2895056 TI - [Expert colloquium: The status of digitalis therapy in heart failure. Mid December 1987, Munich]. PMID- 2895057 TI - Biological effects of the v-erbA oncogene in transformation of avian erythroid cells. PMID- 2895058 TI - Thyroid hormone induced changes in cardiac proteins and mRNAs. AB - Contraction of the hypothyroid heart is characterized by delayed diastolic relaxation and decreased velocity of systolic contraction. In order to determine if these alterations could be mediated by the changes in the mRNA coding for the Ca++ ATPase of the sarcoplasmic reticulum and alterations of the mRNAs coding for myosin heavy chain (MHC) alpha and beta, the levels of these specific mRNAs were quantitated using a Northern blotting technique. We find that the Ca++ ATPase mRNA was 3-fold lower in hypothyroid hearts. After T3 administration to hypothyroid rats, Ca++ ATPase mRNA increased to 66% of control levels within 2 hrs and to 100% of control levels 5 hrs after T3 administration. In the hypothyroid heart, MHC beta mRNA was the predominant message with MHC alpha mRNA barely detectable. Administration of 2 mg of T3 led to a significant increase in MHC alpha mRNA levels first detectable 2 hrs after T3 administration. Twenty-four hrs after T3 administration, MHC alpha mRNA levels had normalized. The results of these studies indicate that thyroid hormone mediates significant alterations in the level of the mRNA coding for the Ca++ ATPase of the sarcoplasmic reticulum and of the mRNAs coding for MHC alpha and beta. Changes in the level of these specific mRNAs resulting in lower levels of the corresponding proteins may explain the delayed diastolic relaxation and the decreased velocity of contraction of the hypothyroid heart. PMID- 2895059 TI - Effects of amiodarone on thyroid hormone-responsive gene expression in rat liver. AB - The hypothesis that amiodarone (AM) acts by inducing a local 'hypothyroid-like' state in thyroid hormone-responsive tissues was investigated in rat liver. Hypothyroid rats, pretreated orally for 8 consecutive days with AM (200 mg/kg) or water, were given a single i.p. injection of equimolar doses of T4, T3 or rT3 (1.00 to 1.20 mg/kg). Six hours later, the rats were killed and liver nuclear T3 receptor occupancy was determined. Simultaneously, the activity of two thyroid hormone-responsive enzymes was measured, together with the levels of their respective mRNAs by hybridization to specific cDNAs. The enzymes were phosphoenolpyruvate carboxykinase and glutamine synthetase. AM showed no effect on nuclear T3 receptor occupancy in rats injected with either vehicle, rT3, or T3, but it completely blocked the increase in receptor occupancy in rats injected with T4. With regard to postreceptor effects, T4 and T3 elicited an approximately two-fold increase in the levels of the mRNAs coding for the two enzymes, whereas rT3 had no effect. The increase of the two mRNAs was potentiated by AM, but this is probably secondary to an AM-induced state of anorexia. Remarkably, this potentiating effect of AM was not observed at the protein-level: enzyme activities were lower in rats pretreated with AM. AM-pretreatment thus results in lower enzyme activity to mRNA ratios for both enzymes, irrespective of hormonal treatment. Therefore, although no conclusions can be drawn about possible effects of AM at the transcriptional level, it is concluded that AM interferes with thyroid hormone responsive gene expression in rat liver at a post-transcriptional level. As a consequence, in the present experimental design the livers of AM treated rats resemble the liver of hypothyroid rats with regard to specific enzyme activities, but not with regard to either nuclear T3 receptor occupancy or the levels of specific mRNAs. PMID- 2895060 TI - New data on thyroid regulation and their implications in thyroid physiopathology and specifically of autoimmune diseases. PMID- 2895061 TI - The anonymous RFLP locus D1S2 is close to PGM1 on chromosome 1. AB - D1S2 was one of the first restriction fragment length polymorphisms (RFLPs) assigned to chromosome 1, but its regional location was unknown. In this paper we present data that place this RFLP into both the genetic map and the physical cytogenetic map. Linkage data maps D1S2 7 cM from PGM1, which is localized to the middle of the short arm at 1p22.1. Southern blot analysis of DNA samples from somatic cell hybrids containing parts of chromosome 1 maps D1S2 proximal to 1p32 and distal to PGM1. PMID- 2895062 TI - Lethal vaccinia infection in cyclophosphamide-suppressed mice is associated with decreased expression of Thy-1, Lyt-2 and L3T4 and diminished IL-2 production in surviving T cells. AB - Prior treatment of C57BL/6J mice with 300 mg/kg of cyclophosphamide (Cy) converts a subclinical infection with vaccinia virus to a lethal disease. This is accompanied by a loss of more than 80% of spleen cells and a decreased capacity, on a cell-for-cell basis, to develop virus-immune cytotoxic T lymphocytes (CTL), although the frequency of CTL precursors among surviving T cells is not greatly modified. Phenotypically, the surviving T cells express low levels of cell surface Thy-1, Lyt-2 and L3T4 and, upon stimulation, are less able to produce IL 2 for more than 1 week following Cy treatment. The defect in capacity to generate CTL effectors both in vitro and in vivo can be corrected by providing an exogenous source of IL-2. These experiments indicate that a single dose of Cy induces changes in T cells that persist throughout the development of an immune response. Such effects are in accordance with the known property of Cy to mediate DNA damage. PMID- 2895065 TI - Regulation of cell-mediated immunity in cutaneous leishmaniasis. AB - There is now good evidence that cell-mediated immunity (CMI) rather than humoral antibody plays a causal role in acquired immunity to leishmaniasis. In genetically susceptible strains of mice, the failure to control the disease progression is associated with a population of Lyt-2-T cells which can prevent the induction or expression of curative CMI and hence exacerbate disease development. Susceptible BALB/c mice can be rendered resistant to L. major infection by prior sublethal dose gamma-irradiation, anti-mu antibody treatment from birth, anti-L3T4 antibody treatment or intravenous (i.v.) or intraperitoneal (i.p.) route of immunisation with killed L. major promastigotes or isolated leishmanial antigens. The route of immunisation, however, appears crucial in the induction of prophylactic immunity. Subcutaneous (s.c.) and intramuscular routes of immunisation with killed promastigotes are not only ineffective, they induce a population of Lyt-2- L3T4+ T cells which inhibit the prophylactic effect of i.v. immunisation. Although both the disease-promoting T cells and the host-protective T cells express the same phenotypic cell surface markers, they differ functionally. Protective T cells produce interferon-gamma (IFN-gamma) and macrophage-activating factor (MAF) when cultured in vitro with leishmanial antigens, whereas the disease-promoting T cells do not. In addition, these latter cells are able to produce substances in their antigen-specific culture supernatant which inhibits the MAF activity of the host protective T cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2895063 TI - [Correlations between beta blockers and the induction of psoriasis]. PMID- 2895064 TI - Contrasuppression and tumor rejection. AB - The growth of a highly progressive MCA-induced tumor 3152-PRO is dependent on the activity of suppressor T cells (Ts). Injection of syngeneic mice with antibodies specific for Ts leads to enhanced tumor transplantation resistance of the 3152 PRO tumor. In addition, injection of recipient mice with highly immunogenic regressor tumors conjugated with trinitrophenyl (TNP) activates a T cell population which also mediates protection to transplantation of TNP-conjugated 3152-PRO tumor cells. One such tumor, 1591-RE, was investigated in detail to determine the phenotype and biologic activity of this T cell population in overcoming Ts cell activity. Induction of transplantation resistance requires the presence of TNP hapten on both the highly regressive immunizing tumor (and not its progressor variant 1591-PRO4), and on the challenge tumor 3152-PRO. The cell population from TNP-1591-RE immunized animals which mediates protection against the transplantation of TNP-3152-PRO is Thy-1+, CD4+, 8-, Lyt1+, I-J+, and Vicia villosa lectin adherent, the identical phenotype to antigen-specific contrasuppressor T cells in the contact sensitivity (CS) response to TNP in vivo. A T cell population of identical phenotype from TNP-1591-RE immunized mice can overcome the effects of antigen-specific Ts cells on PCl-immune cells in the adoptive transfer of CS in vivo. These results suggest that immunoregulatory cells that mediate protection against progressive tumors may be identical in function to antigen-specific contrasuppressor T cells. PMID- 2895066 TI - Immunological characterization of axenic Entamoeba histolytica related antigens. PMID- 2895067 TI - Isolation of mosquito pathogenic Bacillus thuringiensis strains from mosquito breeding habitats in Tamil Nadu. PMID- 2895068 TI - Factors inhibiting parasitism of mosquito larvae by the mermithid nematode (Romanomermis iyengari) in a polluted habitat. PMID- 2895069 TI - Laboratory bioassay of the fungus Leptolegnia ornata (Seyamour) Ohio isolate against seven species in five genera of mosquito larvae and non-target aquatic vertebrates. PMID- 2895070 TI - Effect of a kinin antagonist on the acute antihypertensive activity of enalaprilat in severe hypertension. AB - The purpose of this study was to assess the role of kinins in the acute antihypertensive effect of the converting enzyme inhibitor (CEI) enalaprilat in rats with severe hypertension induced by aortic ligation between both renal arteries. For this study, we used a bradykinin analogue, D-Arg-Arg-Pro-Hyp-Gly Thi-Ser-DPhe-Thi-Arg-TFA, with in vivo antagonistic properties. Hypertensive rats were infused intra-aortically for 15 minutes with either saline (30 microliters/min) or the kinin antagonist (40 micrograms/kg/min). Five minutes after the infusion was begun, a bolus injection of enalaprilat (60 micrograms/kg) was given. The blood pressure of the saline-infused animals decreased 48 +/- 6 mm Hg (from 180 +/- 7 to 132 +/- 7 mm Hg), while that of the rats treated with the antagonist decreased only 21 +/- 4 mm Hg (from 175 +/- 3 to 154 +/- 3 mm Hg). The difference between both decrements was significant (p less than 0.01). In another group of hypertensive animals (n = 9), we measured kinin concentration in plasma from arterial blood before and after administration of CEI (41 +/- 10 vs 68 +/- 20 pg/ml, respectively; NS). These results are consistent with the hypothesis that kinins play a role in the acute antihypertensive effect of CEIs in rats with severe hypertension. However, since arterial blood kinin concentrations were not increased significantly after CEI administration, the effect of the CEI may be due to an increase in tissue kinins, which could act as autacoids regulating vascular resistance. PMID- 2895071 TI - Factors influencing blood pressure and heart rate variability in hypertensive humans. AB - We examined the influence of baroreceptor reflex sensitivity (the increase in pulse interval in response to a phenylephrine-induced increase in blood pressure), age, blood pressure, and beta-adrenergic receptor blockade on the variability of blood pressure and heart rate in essential hypertension. Fifty-six subjects were studied before treatment; intra-arterial blood pressure was recorded outside the hospital for 24 hours. Variability was defined (from all beats occurring while subjects were awake) as the standard deviation about the average waking value for mean arterial pressure (MAP) or pulse interval. The correlation (r) between baroreceptor reflex sensitivity and blood pressure variability was -0.47 (p less than 0.0002). Baroreceptor reflex sensitivity was the only independent determinant of blood pressure variability on multiple regression analysis. Thirty subjects were restudied after 5 months of beta adrenergic receptor blockade. Ambulatory blood pressure was lower during treatment, whereas pulse interval, its variability, and baroreceptor reflex sensitivity were higher. Blood pressure variability was unchanged. The variability of MAP was inversely correlated with baroreceptor reflex sensitivity before (r = -0.42, p less than 0.02) and during (r = -0.45, p less than 0.02) treatment, but it was unrelated to the average ambulatory MAP or to the variability of pulse interval either before or during beta-blockade. Sixteen subjects whose average waking ambulatory blood pressure was 140/90 mm Hg or less were not treated. This group of borderline hypertensive subjects had less variable MAP than did the remaining 40 subjects (12.4 +/- 2.3 [SD] vs 14.5 +/- 2.5 mm Hg; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2895072 TI - Beta-adrenergic receptor blockers. Adverse effects and drug interactions. AB - Adverse effects of beta-adrenergic receptor blocking drugs can be divided into two categories: 1) those that result from known pharmacological consequences of beta-adrenergic receptor blockade; and 2) other reactions that do not appear to result from beta-adrenergic receptor blockade. Adverse effects of the first type include bronchospasm, heart failure, prolonged hypoglycemia, bradycardia, heart block, intermittent claudication, and Raynaud's phenomenon. Neurological reactions include depression, fatigue, and nightmares. It is not yet proven whether the beta 1-selective adrenergic blockers or those with partial agonist activity reduce the overall frequency of adverse reactions seen with propranolol. Patient age does not appear, in itself, to be associated with more beta-blocker side effects. Side effects of the second category are rare. They include an unusual oculomucocutaneous reaction and the possibility of oncogenesis. There are also many drugs that interact with beta-blockers, which may increase toxicity. Finally, there are specific patient characteristics where one beta-blocker may be more effective and safer than another. PMID- 2895073 TI - [Madreporic coral]. PMID- 2895074 TI - Monoclonal antibodies at the electron microscopical level. AB - The ability to monitor cellular events and to identify, morphologically, sub cellular components involved in particular processes has greatly advanced since the advent of monoclonal antibodies (MAbs) and their use in electron immunocytochemistry. For instance, using simultaneous monoclonal and polyclonal antibodies (to proteins and enzymes capable of monitoring intracellular pH) on specially prepared tissue it is now possible to visualize intracellular pathways involved in protein synthesis. The demonstration of coexistence of several substances (e.g., active peptides) in a single cell has been greatly aided by the use of monoclonal and polyclonal antibodies in combination. For light microscopical studies different reaction products are revealed by the use of differently coloured chromogens. For electron microscopy, monoclonal and polyclonal antibodies are labelled with gold particles of different sizes and are used on ultrathin sections (the on-grid immunolabelling or post-embedding method). Low numbers of binding sites on cellular membranes can now be visualised at the electron microscopical level by the use of specific MAbs to receptors or by the construction of divalent forms of antigens that can react with the receptor and subsequently to a MAb. Again, the reaction is revealed by gold labelling procedures. PMID- 2895075 TI - Psychotherapy and pathological grief controlled outcome study. PMID- 2895076 TI - Sudden death. PMID- 2895077 TI - Restriction endonucleases variation in the region of the alcohol dehydrogenase gene: a comparison of null and normal alleles from natural populations of Drosophila melanogaster. AB - The restriction endonuclease variation in the 12 kb region surrounding twelve Adh null alleles extracted from three Tasmanian populations has been compared with normal alleles from the same populations. Each of the null alleles had the same haplotype as revealed by digestions with eight hexanucleotide restriction enzymes. This haplotype also occurred in 4 of the 46 chromosomes bearing normal alleles which were tested; these four chromosomes with the null allele haplotype carried the AdhS allele. The data suggest that the Adh null alleles from geographically separate populations share a common ancestry and are derived from the same mutation in an AdhS allele. PMID- 2895078 TI - Restriction endonuclease digestion and chromosome banding in the mosquito, Culiseta longiareolata (Diptera: Culicidae). AB - Fixed chromosomes of the mosquito, Culiseta longiareolata (2n = 6) were treated in situ with nine restriction endonucleases and stained with ethidium bromide or Giemsa. All the heterochromatic regions were apparently protected from digestion by all enzymes except Mbo I. This enzyme selectively digested one of the three types of heterochromatin present in the species. Staining with the fluorochrome quinacrine after enzyme treatment produced a standard Q-banding pattern or a Hoechst 33258-like pattern, depending on the enzyme. These results confirmed: (a) the presence of three types of heterochromatic containing different DNA fractions in the chromosomes of this species, (b) restriction enzymes accessibility to the DNA of heterochromatin regions, and (c) the selective cleavage of particular DNA fractions without DNA removal. Moreover, quinacrine staining after enzyme digestion proved useful in detecting differential activity among enzymes which produced the same banding pattern with standard dyes. PMID- 2895079 TI - Basic principles in management of basal cell epithelioma. PMID- 2895080 TI - Endocervical culture isolates. PMID- 2895081 TI - Congenital cholesteatoma of the middle ear. PMID- 2895082 TI - Faculty perceptions of student training. PMID- 2895083 TI - Balloon dilatation for aortic stenosis. PMID- 2895084 TI - Pro bono is as pro bono does. PMID- 2895085 TI - ERISA plans to permit assignment of benefits to physicians. PMID- 2895086 TI - From time to time. PMID- 2895088 TI - Physician responsibilities under new AIDS laws. PMID- 2895087 TI - Upcoming primary election signals the start of 1988 races. PMID- 2895089 TI - ISMS positions on AIDS and HIV antibody testing. PMID- 2895090 TI - Teens speak out on sex. PMID- 2895091 TI - Infant mortality. PMID- 2895093 TI - Asking the right questions. PMID- 2895092 TI - Teen suicide. PMID- 2895094 TI - Children as victims. PMID- 2895095 TI - Time out for a checkup. PMID- 2895096 TI - Nothing can replace a good friend. PMID- 2895097 TI - Cimaterol-induced muscle hypertrophy and altered endocrine status in lambs. AB - The objectives of this study were 1) to determine how cellular growth of skeletal muscle is altered by the repartitioning agent cimaterol and 2) to determine if cimaterol alters endocrine status in association with its repartitioning effects. Thirty Dorset wether lambs were randomly assigned to a pre-treatment baseline group or received 0 or 10 ppm cimaterol in a complete, mixed, high-concentrate diet for 7 or 12 wk. Weights of biceps femoris (BF), semimembranosus (SM) and semitendinosus (ST) muscles were 32.8, 27.1 and 31.5% greater, respectively, in treated lambs at 7 wk, and were 22 to 24% greater at 12 wk. Longissimus (LD) cross-sectional area was 26 and 32% greater at these treatment intervals. Percent type I fibers declined significantly over the course of the experiment in ST, SM and LD, and cimaterol caused a small but significant reduction in percent type I fibers in the ST at 7 and 12 wk. Muscles from lambs fed cimaterol contained 50 and 75% more fibers that exhibited negative staining for phosphorylase activity. Mean cross-sectional area of type I and type II fibers in the combined portions of the ST were 30.4 and 29.3% greater, respectively, in cimaterol-fed lambs after 12 wk, while type I and type II fiber areas in the longissimus were only 13 and 15% greater, respectively. Cimaterol-induced hypertrophy of the ST resulted in both protein and RNA content being 30 to 35% greater (P less than .01) at 7 and 12 wk, while DNA concentration was 22% less (P less than .01) at 7 wk. DNA concentration returned to normal by 12 wk. These results indicate that cimaterol elicits a rapid increase in muscle RNA and protein accretion without concurrent incorporation of satellite cell nuclei. Plasma insulin and insulin-like growth factor-1 (IGF-1) concentrations were 55 and 34% lower, respectively, in cimaterol fed lambs. Plasma somatotropin concentration and area under the curve were 2.3 times greater (P less than .01) in lambs fed cimaterol for 6 wk, while plasma cortisol, prolactin and glucose concentration were unaffected at 6 or 12 wk. The significant changes in endocrine status may be important in the mechanism(s) of cimaterol in altering muscle accretion. PMID- 2895098 TI - Effect of combined H-1 and H-2 histamine receptor antagonists on late asthmatic response in an asthmatic patient. AB - A curious inhibitory effect of histamine H-1 and H-2 antagonists on isolated late asthmatic response (LAR) in an asthmatic patient was observed. When given alone, neither the H-1 nor the H-2 antagonist had an effect on LAR. The combination of drugs, however, provided marked inhibition of LAR. These findings suggest that histamine contributes to some types of LAR. PMID- 2895099 TI - Polymorphisms in the umuDC region of Escherichia species. AB - The umuDC operon of Escherichia coli encodes mutagenic DNA repair. The umuDC regions of multiple isolates of E. coli, E. alkalescens, and E. dispar and a single stock of E. aurescens were mapped by nucleotide hybridization. umuDC is located at one end of a conserved tract of restriction endonuclease sites either 12.5 or 14 kilobase pairs long. Rearrangements, including possible deletions, were seen in the polymorphic DNA flanking the conserved tract. Restriction site polymorphisms were not found around the DNA repair gene recA or polA. The junctions of the conserved region contain direct repeats of nucleotide sequences resembling the termini of the Tn3 group of transposons. Possible mechanisms for the generation of these variants are discussed. PMID- 2895101 TI - Regulation of fatty acid degradation in Escherichia coli: fadR superrepressor mutants are unable to utilize fatty acids as the sole carbon source. AB - Localized mutagenesis of the fadR region of the Escherichia coli chromosome resulted in the isolation of two classes of fadR regulatory mutants. The first class was constitutive for the fatty acid degradative enzymes and presumably defective for fadR function. The second class was rarer and resulted in the inability to utilize fatty acids as a sole carbon source (Fad-). These fadR superrepressor mutants [fadR(S)] had greatly reduced levels of the beta-oxidative enzymes required for growth on fatty acids. The fadR(S) mutants reverted to Fad+ at a high frequency (10(-5], and the resulting Fad+ revertants were constitutive for expression of the fad enzymes (fadR). Merodiploid analysis showed the fadR(S) allele to be dominant to both fadR+ and fadR alleles. PMID- 2895100 TI - Molecular cloning and sequencing of the gene encoding the fimbrial subunit protein of Bacteroides gingivalis. AB - The gene encoding the fimbrial subunit protein of Bacteroides gingivalis 381, fimbrilin, has been cloned and sequenced. The gene was present as a single copy on the bacterial chromosome, and the codon usage in the gene conformed closely to that expected for an abundant protein. The predicted size of the mature protein was 35,924 daltons, and the secretory form may have had a 10-amino-acid, hydrophilic leader sequence similar to the leader sequences of the MePhe fimbriae family. The protein sequence had no marked similarity to known fimbrial sequences, and no homologous sequences could be found in other black-pigmented Bacteroides species, suggesting that fimbrillin represents a class of fimbrial subunit protein of limited distribution. PMID- 2895102 TI - Neisseria meningitidis C114 contains silent, truncated pilin genes that are homologous to Neisseria gonorrhoeae pil sequences. AB - Neisseria meningitidis pili can be classified into two groups: those (referred to here as class I pili) which are similar to gonococcal pili in that they react with monoclonal antibody SM1 and those that are dissimilar to gonococcal pili in that they lack the SM1-reactive epitope (class II pili). Pilus expression in N. meningitidis C114, a class II pilus-producing isolate, was investigated. The sole genomic segment of this strain that bore extensive homology with the pilE locus of Neisseria gonorrhoeae P9 was cloned in Escherichia coli. The production of the pilus structural subunit (pilin) from this meningococcal segment could not be detected by immunological and coupled in vitro transcription-translation analyses. Nucleotide sequence analysis revealed the presence in the C114 genome of two variant, tandemly arranged pilin genes (copies 1 and 2). Copies 1 and 2 are partial pilin genes that constitute part of a silent meningococcal pilin gene (pil gene) region, designated pilS. Both copies are truncated, corresponding to variable domains of the gonococcal pilE gene but lacking homologous N-terminal coding sequences. Located within sequences surrounding copies 1 and 2 were several classes of repeated elements that are associated with pil loci in N. gonorrhoeae. PMID- 2895103 TI - Structure and antigenic properties of the tip-located P pilus proteins of uropathogenic Escherichia coli. AB - Pyelonephritogenic Escherichia coli frequently expresses pili which bind to Gal alpha (1-4)Gal receptors present on the uroepithelium. Binding of these pili is mediated by a pilus-associated adhesin, PapG, and not by the major subunit which constitutes the bulk of the pilus structure. The adhesin and two pilinlike proteins, PapE and PapF, are present in only a few copies each at the pilus tip. Surface exposure of both PapF and PapG is required to achieve receptor-specific binding. The nucleotide sequences for the genes encoding the tip-associated proteins PapE, PapF, and PapG were determined for two E. coli clones expressing P pili of serotypes F11 and F7(2) and compared with the corresponding sequences established for proteins of F13 pili. Specific antisera were used to study the cross-reactivity between the F13 tip proteins and the equivalent proteins in F11 and F7(2) pili. We present data showing that, like the major pilus subunit, PapE varies its structure and antigenic properties among pili of different serotypes. In contrast, the PapF protein was highly conserved, and PapF-specific antisera raised against serotype F13 cross-reacted with the PapF proteins of both F11 and F7(2) serotypes. The PapG adhesin protein from F11 and F7(2) pili differed by only five amino acids out of 316 residues. However, the F13 adhesin showed only 45% amino acid homology with the other two variants. PMID- 2895104 TI - A mutation in the alpha-subunit of F1-ATPase from Escherichia coli affects the binding of F1 to the membrane. AB - The mutation Gly-29----Asp in the alpha-subunit of the F1-ATPase from Escherichia coli was characterized and shown to cause the following effects. 1) Oxidative phosphorylation was markedly impaired in vivo 2) Membrane ATPase and ATP-driven proton-pumping activities were decreased markedly. 3) Membranes were proton permeable, and membrane-bound ATPase was dicyclohexylcarbodiimide-insensitive. Therefore, it appeared that integration between F1 and F0 was abnormal. This was confirmed directly by the demonstration that the mutant F1 bound poorly to stripped membranes from a normal strain. Purified, soluble mutant F1 had normal ATPase activity. These results suggest that residue Gly-29, which is strongly conserved in alpha-subunits of F1-ATPases, lies in a region of the alpha-subunit important for membrane binding. Thus, three regions of the F1-alpha-subunit have now been recognized, specialized for membrane binding, nucleotide binding, and alpha/beta intersubunit signal transmission, respectively. The approximate locations of the three regions are described. PMID- 2895105 TI - The isolation and purification of a specific "protector" protein which inhibits enzyme inactivation by a thiol/Fe(III)/O2 mixed-function oxidation system. AB - Mixed-function oxidation systems comprised of Fe3+, O2, and electron donors such as thiol compounds, ascorbate, NAD(P)H/NAD(P)H oxidase, and xanthine oxidase/hypoxanthine, catalyze the inactivation of many enzymes. This report describes the isolation and purification of a soluble protein from Saccharomyces cerevisiae, which specifically inhibits the inactivation of various enzymes by a nonenzymatic Fe3+/O2/thiol mixed-function oxidase system. When thiol is replaced with another electron donor (e.g. ascorbate), this specific protein no longer protects against iron (or copper)/O2-dependent radical-induced enzyme inactivation. Purification steps included a polyethylene glycol precipitation followed sequentially by a chromatography on DE52 and high pressure liquid chromatography on phenyl, DEAE, and gel-filtrated columns. The final gel filtration step yielded two protein peaks exhibiting protector activity and possessing a Mr of 500,000 and 90,000. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of these two fractions gave a single band at 27 kDa suggesting that these protein species simply represent different oligomeric structures. The protector protein did not possess catalase, glutathione peroxidase, superoxide dismutase, or iron chelation activities. Since the protection activity reported herein is specific for mixed-function oxidation systems containing thiols, we propose that the protector protein functions as a sulfur radical scavenger. PMID- 2895106 TI - Directed mutations of the strongly conserved lysine 155 in the catalytic nucleotide-binding domain of beta-subunit of F1-ATPase from Escherichia coli. AB - The amino acid sequence -Gly-X-X-X-X-Gly-Lys- occurs in many, diverse, nucleotide binding proteins, and there is evidence that it forms a flexible loop which interacts with one or other of the phosphate groups of bound nucleotide. This sequence occurs as -Gly-Gly-Ala-Gly-Val-Gly-Lys- in the beta-subunit of the enzyme F1-ATPase, where it is thought to form part of the catalytic nucleotide binding domain. Mutants of Escherichia coli were generated in which residue beta lysine 155, at the end of the above sequence, was replaced by glutamine or glutamate. Properties of the soluble purified F1-ATPase from each mutant were studied. The results showed: 1) replacement of lysine 155 by Gln or Glu decreased the steady-state rate of ATP hydrolysis by 80 and 66%, respectively. 2) Characteristics of ATP hydrolysis at a single site were not markedly changed in the mutant enzymes, implying that lysine 155 is not directly involved in bond cleavage during ATP hydrolysis or bond formation during ATP synthesis. 3) The binding affinity for MgATP was weakened considerably in the mutants (Lys much much greater than Gln greater than Glu), whereas the binding affinity for MgADP was affected only mildly (Lys = Gln greater than Glu), suggesting that lysine 155 interacts with the gamma-phosphate of ATP bound at a single high affinity catalytic site. 4) The major determinant of inhibition of steady-state ATPase turnover rate in the mutant enzymes was an attenuation of positive catalytic cooperativity. 5) The data are consistent with the idea that during multisite catalysis residue 155 of beta-subunit undergoes conformational movement which changes substrate and product binding affinities. PMID- 2895107 TI - The zonation of liver and the distribution of fructose 2,6-bisphosphate in rat liver. AB - Livers of starved rats refed for 2 h were perfused in situ by a modification of the dual digitonin pulse technique of Quistorff and Grunnet (Quistorff, B., and Grunnet, N. (1987) Biochem. J. 243, 87-95). A pulse of digitonin (2 mg/ml) was infused first antegrade through the portal vein followed retrograde through the vena cava, or in reverse order, 13 mg of digitonin per zone. Microscopic examination showed that this procedure permeabilized the periportal and perivenous zones of the liver without overlap, with a narrow unaffected band of hepatocytes between the zones. The distribution pattern between periportal and perivenous zones ratio for alanine transaminase, lactate hydrogenase, fructose 1,6-bisphosphatase, and phosphoenolpyruvate carboxykinase ranged from 1.5 to 3. Glucokinase activity was higher in the perivenous zone (periportal/perivenous ratio of 0.7) and glutamine synthetase was exclusively present in that zone. Fructose 2,6-bisphosphate concentration was nearly equal in the two zones. PMID- 2895108 TI - Neurogenic vasodilatation produced by fenoldopam in the rat hindquarters vascular bed. AB - 1 The effects of local administration of the selective DA1-receptor agonist fenoldopam into the isolated autoperfused rat hindquarters were studied in order to investigate the site of action of fenoldopam in this vascular bed. 2 Bolus injections of fenoldopam produced reductions in perfusion pressure in the preconstricted, constant flow perfused rat hindquarters vascular bed. 3 The vasodilator effect of fenoldopam was abolished by sectioning of the lumbar sympathetic nerves and by pretreatment with the ganglion-blocker hexamethonium or the alpha-adrenoreceptor antagonists phentolamine and prazosin. At the same concentration, local infusion of fenoldopam had no effect on vasoconstrictor responses to locally administered noradrenaline and phenylephrine. 4 The vasodilator effect of fenoldopam was antagonized by the non-selective dopamine receptor antagonist RS-sulpiride and by the selective DA1-receptor antagonist SCH 23390, but not by the selective DA2-receptor antagonist domperidone. 5 These results provide no evidence for the presence of postsynaptic DA1-receptors in the rat hindquarters vascular bed; they show that fenoldopam induces neurogenic vasodilatation in this vascular bed, probably via stimulation of ganglionic DA1 receptors. PMID- 2895109 TI - Preneoplastic rat liver cells in vitro: slow progression without promoters, hormones, or growth factors. AB - In order to determine early changes in liver cells during carcinogenesis and to compare them with normal or neoplastic hepatocytes, an experimental model was established which allowed enrichment of this population at early stages of carcinogenesis and provided sufficient viable material for biochemical and cytogenetic analysis. This paper describes a method that allows in vitro selection and propagation of hepatocytes after in vivo initiation by alkylating agents, without the use of hormones, growth factors, or promoters which might affect their progression. From 6 different rat livers (5 initiated by continuous diethylnitrosamine feeding, 1 by a single exposure to N-methyl-N-nitrosourea) we established slow-growing lines, each of which had its own typical characteristics of growth behavior, morphology, and chromosome number. One of these lines (CL 38) transformed spontaneously after 8 weeks in primary culture, with an abrupt change to typical tumor cell behavior such as focal growth, anchorage independence, cloning ability in soft agar, and tumorigenicity in nude mice and newborn rats. In none of the other lines (now in culture for 11-15 months) has a similar abrupt change yet been observed, but all of them show a steady, albeit slow progression towards the properties of neoplastic liver cells, together with a reduction in chromosome number. PMID- 2895110 TI - Plasma glutamate concentration and lymphocyte activity. AB - Elevated glutamate concentrations are commonly observed in tumor patients, and glutamate was recently found to competitively inhibit the membrane transport of cystine. We therefore investigated the possibility that elevated plasma glutamate levels may damage the immune system. The experiments in this report demonstrate a link between the individual plasma glutamate level and the individual immunological reactivity as measured by mitogenic responses. This correlation has been analyzed in 39 colorectal carcinoma patients, 40 oat cell carcinoma patients, 24 large cell lung carcinoma patients, and 31 apparently healthy persons (blood donors). Blood cells from all three groups of tumor patients in comparison with cells from healthy persons produced markedly reduced mitogenic responses against PWM, and all three groups of tumor patients had on average significantly elevated plasma glutamic acid concentrations. Our analysis revealed a linear regression of the logarithm of the individual plasma glutamate levels (before therapeutic treatment) on the logarithm of the corresponding mitogenic reactivity against PWM for the entire population of 134 persons tested (correlation coefficient -0.80; level of significance P less than 0.00001). A statistically significant linear correlation with a similar regression equation was also observed in the group of the healthy blood donors (n = 31; correlation coefficient -0.56; P less than 0.01), indicating that this correlation is universal and not dependent on the presence of a tumor. Mitogenically stimulated murine lymphocyte cultures revealed an inverse correlation between glutamate concentration and cell proliferation in response to the mitogens PHA and PWM. PMID- 2895113 TI - Pheochromocytoma: was diagnosis delayed? PMID- 2895111 TI - Promoting activity of di(2-ethylhexyl)phthalate in rat liver foci bioassay. AB - The plasticizer DEHP but not DEHS exerted a weak promoting effect in a 12-week rat liver foci bioassay, using weanling female Sprague-Dawley rats. The effect was similar after doses of 200 and 500 mg/kg body weight, given 3 times weekly by gavage for 11 consecutive weeks after initiation with a single oral dose of 8 mg DEN/kg body weight. Lower doses were ineffective. The incidence of foci with deficiency in ATPase was enhanced about twice compared to rats treated with DEN only. The incidence of foci with expression of GGTase was not affected by DEHP treatment. The results match the findings with lifetime exposure studies, when liver tumors were found in rats and mice. The actual risk for man from environmental DEHP contamination seems to be low; the intake from highly contaminated food is calculated to be about 400-fold lower than the lowest effective dose in this study. PMID- 2895114 TI - Analysis of drugs from biological fluids using disposable solid phase columns. AB - The traditional liquid-liquid extraction method for the removal of drug from biological matrix is being superseded by solid phase extraction. This involves the selection of an appropriate sorbent (normal-phase, reversed-phase, ion exchange etc.), but once this has been achieved the method is quick and simple to operate. Most sample handling losses are avoided so recovery of drug is high and it is easily automated. Disposable columns have several advantages. Samples of 0.05-2.0 ml can be analysed routinely. Several wash stages can be included in a method to provide a specific extraction prior to a quick analysis by high performance liquid chromatography (HPLC), radioimmunoassay, UV etc. A potential problem is that retention of the drug may involve more than one mechanism. Elution of drug may therefore require a stronger eluting solvent than analytical HPLC systems using the same stationary phase. PMID- 2895112 TI - Dietary effects on initiation and promotion of hepatocarcinogenesis in rat. AB - Female F344/N rats were initiated with DEN (10 mg/kg) 24 h after a 70% partial hepatectomy. Groups of 10 rats were fed (a) AIN, group-1; (b) PD, group-2; or (c) NIH, group-3, for 1 week after initiation and were then fed NIH plus the promoting agent PB at a level of 0.05% in the diets for 6 months. Other groups were fed NIH for 1 week after initiation and then NIH without PB (group-4), AIN + PB (group-5), AIN without PB (group-6), PD + PB (group-7), or PD without PB (group-8) for 6 months. The numbers and volume percentages of AHF were quantified by stereologic methods from frozen serial sections, stained consecutively for GGT, ATPase, and G6Pase. For the groups fed different diets during the 1st week after initiation, the numbers and volume of AHF were significantly greater in group-2 than in groups 1 or 3. The numbers of AHF were significantly less in group-3 than in group-1. The numbers and volume of AHF were significantly greater in groups fed PB during the promotion phase, except in the case of group-7, whose focal volume did not differ from groups 6 or 8. Group-3 had significantly greater numbers of AHF than groups 5 and 7. These findings can be explained by the hypothesis that the NIH diet contained factors that acted synergistically with PB to enhance tumor promotion. The mean focal volume of both GGT positive and ATPase negative foci was significantly greater in group-5 than in all other groups; this indicates that the AIN + PB regimen selectively promoted the growth of a subpopulation of AHF. These findings show that alterations in the composition of diets fed during hepatocarcinogenesis significantly alter the effects of specific chemical agents acting during the stages of initiation and promotion in hepatocarcinogenesis. PMID- 2895115 TI - Direct determination of the enantiomeric purity of (5S)-3-isopropyl-5-p toluenesulphonyloxymethyloxazolidin-2-one on a cellulose-based chiral stationary phase. In-process control of a chiral intermediate used in the synthesis of enantiomerically pure beta-blocking agents. PMID- 2895116 TI - High-performance liquid chromatographic determination of a new H2 blocker (ORF 17 910) in plasma. PMID- 2895117 TI - Combined high-performance liquid chromatographic-radioimmunoassay method for the analysis of endorphins, enkephalins and other neurotransmitter peptides. AB - Assays for beta-endorphin (BE) and its precursors such as beta-lipotropin (LPH) in cerebrospinal fluid (CSF), plasma and some tissues have been difficult because of their low concentrations in limited sample volumes, the non-specificity of most antisera. These problems are compounded by the lack of suitable separation methods. Similar problems exist for the enkephalins, tachykinins and dynorphins, among others. This study reports a high-performance liquid chromatographic (HPLC) separation method in which BE and LPH are well separated from each other and which also separates other neuropeptides of interest. The method uses volatile solvents which do not interfere with radioimmunoassay (RIA). Thus by combining HPLC with RIA the method offers, for the first time, a specific assay method for the endorphin, enkephalin and dynorphin families of peptides which does not suffer from the uncertainties in RIA due to cross-reactivities of antisera. Peptide concentrations obtained from the CSF of a small group of chronic pain patients are also presented. PMID- 2895118 TI - The effect of selective dopamine-1 receptor stimulation on renal and adrenal function in man. AB - We studied the actions of iv fenoldopam, a selective dopamine-1 (DA-1) receptor agonist, in 10 normal men eating a diet containing 150 meq sodium and 60 meq potassium per day. During DA-1 receptor stimulation systemic hemodynamic function did not change. Fenoldopam resulted in an increase in urine flow rate from 13 +/- 1 (+/- SE) to a peak of 17 +/- 2 mL/min (P less than 0.05) and an increase in renal plasma flow from 344 +/- 39 to 481 +/- 44 mL/min (P less than 0.05). Urinary sodium excretion and fractional excretion of sodium both increased. Urinary sodium excretion rose to a maximum of 0.32 +/- 0.05 compared with a control value of 0.21 +/- 0.03 meq/min (P less than 0.01), while fractional excretion of sodium rose to 2.7 +/- 0.6 compared with a control value of 1.6 +/- 0.1% (P less than 0.05). The glomerular filtration rate did not change. Administration of a predominantly DA-2 antagonist during continuous DA-1 receptor stimulation did not block the fenoldopam-induced natriuresis. The rise in plasma aldosterone concentration after metoclopramide administration was blunted by DA-1 receptor activation [19.2 +/- 2.9 during control compared with 12.7 +/- 1.3 ng/dL (P less than 0.01) during fenoldopam]. No change occurred in serum potassium, plasma cortisol, or PRA. We conclude that selective DA-1 receptor stimulation in man produces sustained natriuresis and inhibition of aldosterone release by direct renal and adrenal effects. PMID- 2895119 TI - Long term treatment with the somatostatin analog SMS 201-995 in a patient with a thyrotropin- and growth hormone-secreting pituitary adenoma. AB - A patient with a mixed pituitary tumor secreting TSH and GH was treated, starting 3 months after partial adenomectomy, with the somatostatin analog SMS 201-995 for 8 months. Somatostatin itself inhibited TSH, GH, and alpha-subunit release by the tumor both in vivo and in vitro. Long term treatment with twice daily sc injections of SMS 201-995 resulted in decreased TSH secretion and lower serum thyroid hormone levels. However, euthyroidism was achieved only when the patient was treated with three daily 200-micrograms injections of SMS 201-995. After 30 weeks of SMS 201-995 therapy, TSH secretion increased, while GH secretion remained suppressed. After withdrawal for 6 months, SMS 201-995 (100 micrograms, sc, twice daily) again completely inhibited TSH secretion. SMS 201-995 did not alter the volume of the residual adenomatous tissue. We conclude that SMS 201-995 may be a valuable therapeutic agent for the management of patients with a thyrotroph adenoma. However, desensitization may occur during long term treatment. PMID- 2895120 TI - Neonatal thyroid disease: differential expression in three successive offspring. AB - Neonatal thyroid disease, manifested as either hyperthyroidism or hypothyroidism, has been described in the offspring of women with autoimmune thyroid disorders. We report clinical and laboratory observations in a mother with autoimmune thyroiditis who gave birth to three children with different forms of thyroid dysfunction. The first child was clinically normal, the second child had transient neonatal hyperthyroidism, and the third child had neonatal hypothyroidism. After the birth of the second child, the mother was found to be biochemically hypothyroid. Long-acting thyroid stimulator and antithyroid microsomal antibodies were detected in her serum. She was treated with L-T4 (0.15 mg/day). After the birth of her third child, the mother was found to have thyroid stimulating immunoglobulins and TSH-blocking inhibitory immunoglobulins in her serum. The latter also were detected in the third newborn. Six weeks later, TSH blocking inhibitory immunoglobulins were not detected in the child, but they persisted in the mother. This report further expands the spectrum of neonatal thyroid disease and suggests that differing disease syndromes in the newborn can occur depending on whether stimulating or blocking antibodies predominate in the mother. PMID- 2895121 TI - Neural control of ovulation. AB - Pituitary gonadotrophin function is controlled to a great extent by the central nervous system and by the feedback action (positive and negative) of sex steroids. Neural structures involved in this mechanism may be divided into two levels. The first level is represented by the nervous structures releasing gonadotrophin-releasing hormone (GnRH) in a pulsatile manner into the portal circulation. The gene encoding the precursor protein for GnRH has been described recently. The precursor protein appears to be composed of 92 amino acids, in which the GnRH decapeptide is preceded by a signal peptide and followed by a peptide termed GAP for GnRH-associated peptide. The GnRH-synthesizing neurones and the nervous structures synchronizing the GnRH discharge (pulse generator) in the monkey, and probably also in the human, reside in the medial basal hypothalamus, which appears to have a highly integrated structure. The GnRH pulse generator is influenced by nervous structures outside the medial basal hypothalamus (second level of control) as well as by ovarian and other hormones. These influences probably impinge directly or indirectly on the hypothalamic oscillator. Concerning the chemical nature of the substances mediating the action, a large number of neurotransmitters and neuropeptides have been reported to influence GnRH secretion. PMID- 2895122 TI - Exocytosis in normal anterior pituitary cells. Quantitative correlation between growth hormone release and the morphological features of exocytosis. AB - We have used high-pressure freezing techniques to study exocytosis in rat anterior pituitary cells. The cells were either unstimulated or exposed to 1 nM growth hormone releasing factor (GRF) for 10 min before ultrarapid freezing. The magnitude of growth hormone (GH) release was then correlated with the number of exocytotic events observed with freeze-fracture electron microscopy. High pressure freezing of unfixed and uncryoprotected specimens permits cryofixation of samples up to 1 mm diam (0.5 mm thick) without ice crystal damage, and arrests exocytotic events within 10 ms. Our studies comparing conventionally fixed specimens with those prepared by high-pressure freezing confirm that areas of intramembrane particle clearing at potential exocytotic sites are an artifact of conventional fixation and/or cryoprotection techniques. The cells exposed to 1 nM GRF released approximately fivefold more GH than did unstimulated cells. Morphologically, we have observed a 3.3-fold increase in the number of exocytotic events in GRF-stimulated cells, 33.7 events/100 micron2 compared with 10.4 events/100 micron2 for unstimulated cells. In additional experiments, we studied the effects of two inhibitors of GRF-induced exocytosis, somatostatin and sodium isethionate. Both compounds elicit the same response, a parallel decrease in exocytotic events and in secreted product. We conclude that high-pressure freezing, combined with freeze-fracture and freeze-substitution processing techniques, is an excellent tool for studying the morphological aspects of exocytosis. In the present investigation, it has allowed us to quantitatively relate the biochemistry and morphology of exocytosis in anterior pituitary cells. PMID- 2895124 TI - The antibacterial effect of toothpastes on the salivary flora. AB - Both past and presently available toothpastes contain potential antimicrobial agents which could have a beneficial effect in the prevention of plaque and gingivitis. If these preparations were to be effective clinically, some effect on salivary bacteria would also be expected. This cross-over study measured salivary bacterial counts and the presence or absence of residual antibacterial activity in saliva following tooth brushing with 7 commercially available toothpastes, and moreover, compared their effect with that produced by a chlorhexidine gel. Generally, all toothpaste products produced a reduction in aerobic, anaerobic and streptococcal counts with a hexetidine containing toothpaste producing the largest and longest lasting reduction. In contrast, an enzyme containing toothpaste and an amine fluoride toothpaste, had little effect on bacterial counts. The chlorhexidine gel produced the largest reduction in salivary counts, which was evident for at least 5 h following brushing. Residual antibacterial activity in saliva was only evident immediately following brushing with the hexetidine toothpaste, but for the chlorhexidine gel, was present up to 90 min following brushing. The findings of this study have illustrated the limited antibacterial activity of presently available toothpastes on the salivary flora compared to chlorhexidine, and as such, would tend to question the relative benefit of toothpaste in preventing periodontal disease through an antimicrobial effect. PMID- 2895126 TI - Prediction of response to antipsychotics. AB - This review surveys the literature in the area of predictors of response to antipsychotic drugs. Four general categories are presented and discussed: diagnosis as a predictor, clinical predictors, biological predictors, and pharmacological predictors. No single consistent predictor of response could be discerned; it appears that a variety of factors affect outcome and that several variables must be considered simultaneously. Based on the findings of this review, suggestions for improvements in clinical research design are made. PMID- 2895123 TI - Genetic linkage of two intragenic restriction fragment length polymorphisms with von Willebrand's disease type IIA. Evidence for a defect in the von Willebrand factor gene. AB - Restriction fragment length polymorphisms (RFLPs), using the enzymes Bgl II and Xba I in conjunction with human von Willebrand factor (vWF) cDNA probes, have been described previously. In the present study we demonstrate the localization of both genetic markers within the vWF gene. The RFLPs were used to study the segregation of alleles associated with von Willebrand's disease (vWD) type IIA in a comprehensive, affected family. Individuals of this family were tested for their bleeding time and their plasma was analyzed for vWF antigen concentration and vWF ristocetin-cofactor activity. Based on these data, the affected members were diagnosed as vWD type-IIA patients; this conclusion was confirmed by the analysis of the multimeric vWF pattern of some of the patients. It was demonstrated that both RFLPs are completely linked with the vWD type-IIA trait. From this finding, we conclude that the defect that causes the vWD type IIA is most likely due to a mutation in the vWF gene and not to a mutation in a gene involved in posttranslational processing of the vWF protein. PMID- 2895125 TI - Pharmacokinetics and pharmacodynamics of oral nizatidine. AB - Nizatidine was studied in six high-acid-secretor (basal secretion, greater than or equal to 5 mEq/hr) male volunteers in a randomized, double-blind, nonbalanced, cross-over, placebo and standard drug-controlled study. Doses of 75 mg, 150 mg, and 300 mg bid were compared with placebo and cimetidine 300 mg qid. Nocturnal acid output was significantly reduced (P less than .01) by all doses of nizatidine (36 +/- 22, 36 +/- 31, and 26 +/- 20 mEq) with 75 mg, 150 mg and 300 mg, respectively, and also by cimetidine (43 +/- 39 mEq) as compared with placebo (101 +/- 61 mEq). Nizatidine also significantly reduced meal-stimulated acid secretion at breakfast (14 +/- 9, 9 +/- 7, and 5 +/- 6 mEq/2 hours with 75 mg, 150 mg, and 300 mg, respectively, P less than .01), at lunch (50 +/- 22, 57 +/- 22 and 50 +/- 35 mEq/2 hours, P less than .05) but did not have any effect at dinner (65 +/- 16, 78 +/- 24, and 71 +/- 17 mEq/2 hours) whereas cimetidine, given every 6 hours, significantly (P less than .01) reduced meal-stimulated acid secretion (25 +/- 16, 27 +/- 20 and 31 +/- 15 mEq/2 hours, breakfast, lunch, and dinner, respectively) as compared with placebo (81 +/- 30, 76 +/- 25, and 66 +/- 16 mEq/2 hours, breakfast, lunch, and dinner, respectively). Both drugs have a similar pharmacokinetic profile. Nizatidine seems to be a promising H2 antagonist, more potent than cimetidine (on an mg/mg basis), and efficacy studies on gastric acid disorders should be performed. PMID- 2895128 TI - Experimental selection for insecticide resistance. PMID- 2895127 TI - Pilot study of alpidem, a new nonbenzodiazepine anxiolytic, in the treatment of generalized anxiety disorder. PMID- 2895129 TI - Balance among autonomic controls of heart rate in neonatal spontaneously hypertensive and borderline hypertensive rats. AB - The ontogeny of functional sympathetic neural, adrenal medullary, and extra adrenal components of adrenergic control of heart rate was compared in neonatal Spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Borderline hypertensive (BHR) rats using combined sequential pharmacological blockade and surgical intervention. Baseline heart rate recorded from awake and unrestrained pups was lower in BHR than in WKY or SHR at 5 days of age. Tonic sympathetic neural control of heart rate was inferred from bradycardia after treatment with the adrenergic neuron-blocking agent, bretylium tosylate. Bradycardia after bretylium treatment was observed at 2, 5 and 8 days of age in all strains, suggesting tonic sympathetic neural control of heart rate during the first postnatal week. Parasympathetic control of heart rate was inferred from heart rate increase after treatment with the muscarinic receptor blocker, atropine methyl nitrate, in pups pretreated with bretylium. Tachycardia following atropine methyl nitrate was substantial in all 24-day-old pups. Control of heart rate by neurally mediated release of catecholamines from the adrenal medulla was inferred from bradycardia following administration of the ganglionic blocking agent, hexamethonium, to pups pretreated with bretylium and atropine methyl nitrate. Heart rate decreases after hexamethonium were found in 2-day-old WKY and BHR pups, and at 5 and 8 days in all strains. Adrenalectomy was performed in additional animals to confirm the adrenal catecholamine influence on heart rate. The influence of residual circulating catecholamines on neonatal heart rate was inferred from bradycardia following administration of the beta-adrenergic receptor blocking agent, atenolol, in pups pretreated with bretylium, methylatropine, and hexamethonium. Bradycardia was observed in pups of each strain and at all ages after atenolol treatment. Strain differences in autonomic controls of heart rate were most pronounced at 24 days of age. At 24 days of age both SHR and BHR pups showed increased adrenal catecholamine and parasympathetic influences on heart rate compared to WKY. Thus, prior to weaning, rats differing in their genetic predisposition to hypertension showed a unique pattern of autonomic control over heart rate which may be related to adult cardiovascular regulation. PMID- 2895130 TI - Inhibitory effects of atropine and adrenergic antagonists on the changes in autonomic receptors and cyclic nucleotides of rat parotid and submandibular glands caused by sympathetic nerve stimulation. AB - The changes in cyclic AMP (cAMP) concentration and density of beta-adrenoceptors caused by electrical stimulation of the sympathetic innervation to parotid and submandibular glands of rat did not occur when the alpha- and beta-adrenergic antagonists, phentolamine, and propranolol were administered 20 min prior to initiation of stimulation. They also did not occur when phentolamine, the beta adrenergic antagonist, was administered alone prior to nerve stimulation, indicating that beta-adrenoceptors mediate these effects. Simultaneous administration of the alpha- and beta-antagonists also prevented the changes in densities of muscarinic receptors and cGMP concentrations usually induced by sympathetic nerve stimulation. Also, the changes in muscarinic receptors and cGMP did not occur when atropine was administered prior to nerve stimulation, nor did they occur with simultaneous administration of atropine, phentolamine + propranolol; with phentolamine alone, or propranolol alone, the effects were blocked to a large extent. Secretion was inhibited completely when both adrenergic antagonists were present during nerve stimulation, but flow rate was unchanged when atropine was present. The changes in both beta-adrenoceptors and muscarinic receptors reflect a desensitization caused by prolonged exposure to neurotransmitters released when the sympathetic nerve is stimulated. The changes are prevented when either atropine or adrenergic antagonists are present during nerve stimulation. PMID- 2895131 TI - The actions of myelinated and non-myelinated vagal fibres on atrial contraction in the rabbit. AB - The bradycardia and reduction in atrial contraction on electrical stimulation of the peripheral cut end of the vagus nerve in the cat have been attributed solely to the action of myelinated fibres. In the rabbit however, recruitment of non myelinated fibres produces an additional prolonged bradycardia. The objective of this investigation was to examine the relative contributions of myelinated and non-myelinated fibres to the vagal action on atrial contraction in the rabbit. In 5 rabbits stimulation of myelinated fibres at 10 Hz for 20 s reduced developed atrial tension of the paced heart by 17.1 +/- 2.6%. After stimulation, atrial tension returned rapidly to the control value in 6.5 +/- 0.5 s. Recruitment of non-myelinated fibres resulted in a reduction in developed atrial tension of 29.1 +/- 2.8%. This larger fall in atrial tension outlasted the period of stimulation by 34.1 +/- 4.8 s. Hexamethonium blocked the reduction in atrial contraction due to myelinated fibres but not that due to non-myelinated fibres. Atropine abolished all effects of vagal stimulation on atrial contraction. We conclude that the recruitment of non-myelinated fibres produces an additional prolonged reduction in atrial contraction which is resistant to hexamethonium but blocked by atropine. PMID- 2895132 TI - Ischemic injury of the hand from intra-arterial propylhexedrine injection. AB - A number of adverse consequences can result in the upper limb from parenteral drug abuse. Propylhexedrine, a drug similar to amphetamine, is easily obtained and causes severe injury to the limb when injected intra-arterially. This report describes an inadvertent case of intra-arterial propylhexedrine injection into the radial artery, the natural course of which resulted in digital amputations. The cause and diagnosis of this injury is discussed, and a protocol for treatment is presented. PMID- 2895133 TI - Methicillin-resistant Staphylococcus aureus: report of an outbreak in a London teaching hospital. AB - An outbreak with a strain of methicillin-resistant Staphylococcus aureus began in The London Hospital in 1982 and continues to be associated with significant morbidity and mortality. This particular strain, termed epidemic methicillin resistant S. aureus, is recognized by its characteristic antibiogram, phage-type and plasmid profile. In this outbreak various means of control have been attempted. Sideroom isolation did not curtail spread of the organism and containment was only achieved with the combination of extended screening, mupirocin for treatment of carriage and the use of an isolation ward. PMID- 2895134 TI - Measuring the saving attributable to an antibiotic prescribing policy. AB - An analytical framework is suggested for the economic evaluation of policies to improve the management of hospital infection. Consideration of the costs and benefits to be expected from improved policies implies the existence of an optimal infection rate which is higher than the minimum attainable. It follows that hospitals can and probably do spend too much on infection control in, at least, some areas. This optimal approach is not operational at present but its data requirements might be thought of as an agenda for future research. In the meantime, progress in infection control economics depends on a piecemeal approach. An example is given in the estimation of the cost savings attributable to an improved antibiotic prescribing policy at the Royal Liverpool Hospital. PMID- 2895135 TI - Observations on multiple drug resistance in coagulase-negative staphylococci isolated in hospitals from 1975 to 1985. AB - Drug resistance in coagulase-negative staphylococci (CNS) isolated in hospitals since 1975 was analysed using routine laboratory data registered on a microcomputer. Resistance increased substantially in CNS during the years, especially in Staphylococcus epidermidis isolates, of which more than 50% were multiply drug resistant by 1985. Among the methicillin-resistant CNS strains, resistance to gentamicin rose from 0% in 1975 to 76% in 1985. Co-resistance to kanamycin, gentamicin, and in some cases netilmicin seemed to replace co resistance to kanamycin and streptomycin in S. epidermidis. Gentamicin and netilmicin usage in hospital increased tenfold from 1976 to 1985. PMID- 2895137 TI - Contamination of detergent cleaning solutions during hospital cleaning. AB - Twenty-two detergent cleaning solutions from different ward areas were sampled for bacteria when freshly prepared, during use and at discard. Contamination, mainly by Gram-negative bacilli, was found in 10 freshly prepared solutions and in 21 of the 22 at discard. Preliminary studies showed that the detergent solution was bactericidal to Staphylococcus aureus but allowed the survival but not multiplication of Escherichia coli. PMID- 2895136 TI - Epidemiology of macrolide and lincosamide resistance in species of staphylococci in a general hospital. AB - During a 1-year period resistance to macrolides and lincosamides among staphylococci in a general hospital was studied. The macrolide-lincosamide resistance phenotype was found in 36.7% of coagulase-negative and in 3.7% of coagulase-positive species. Isolates showing this phenotype were more abundant from indwelling artificial devices, blood, respiratory tract and sterile fluids. The surgery and intensive care units of the hospital provided the highest proportion of such strains. Methicillin resistance was present in 13.9% of the staphylococci but no relationship between methicillin and macrolide-lincosamide resistance was observed. PMID- 2895138 TI - Hospital-acquired infections among obstetric and gynaecological patients at Tikur Anbessa Hospital, Addis Ababa. AB - Seven hundred patients admitted to the wards of the Department of Obstetrics/Gynaecology of Tikur Anbessa Hospital, Addis Ababa, between January and July 1984 were studied for the incidence of nosocomial infections. The overall hospital infection rate was 17.0%, with wound infection at 47% followed by urinary-tract infection at 15%. Over 80% of the bacterial isolates were Gram negative bacteria, the majority of which were multiply resistant to the commonly used antibacterial drugs. Some hospital risk factors have been identified. The findings are discussed in the light of reports on nosocomial infections from hospitals of developed countries. PMID- 2895139 TI - Comparison of sodium hypochlorite and sodium dichloroisocyanurate disinfectants: neutralization by serum. AB - A comparison has been made of the activity against Pseudomonas aeruginosa of sodium hypochlorite (NaOCl) and sodium dichloroisocyanurate (NaDCC) solutions containing 0-40% and 0-70% horse serum respectively. The degree of inactivation of NaOCl and of NaDCC solutions by different concentrations of horse serum is expressed in terms of a neutralization coefficient, which demonstrates that NaDCC solutions are less prone to inactivation by serum than are NaOCl solutions, the disparity diverging as serum concentration is increased. In 30% serum an NaDCC solution containing 4000 ppm of available chlorine exhibited similar bactericidal activity to an NaOCl solution containing 17,000 ppm available chlorine. PMID- 2895140 TI - Antimicrobial properties of antiseptic-impregnated biological dressings. AB - Three antiseptics--chlorhexidine acetate, silver nitrate and povidone-iodine- were incorporated into biological dressings (human skin and amnio-chorion) and evaluated in vitro against disparate micro-organisms. Results indicated that antimicrobial levels of chlorhexidine and silver were released from the dressings over a clinically relevant time period, whereas povidone-iodine was ineffective. Chlorhexidine dressings demonstrated broad-spectrum activity, whereas silver dressings were most effective against Pseudomonas aeruginosa. PMID- 2895141 TI - Isolation of organisms in CAPD peritonitis: use of nutrient broth cultures and Bactec blood culture media. AB - Cultures of the first cloudy dialysates from 51 consecutive episodes of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis were carried out using concentrated nutrient broth and Bactec blood culture media in addition to primary culture on solid media. Thirty-seven episodes (73%) were positive on solid media, and 42 episodes (82%) were positive by both nutrient broth and Bactec methods. The value of Gram-stained smears and WBC counts on dialysates is discussed. PMID- 2895142 TI - Perforations in surgeons' gloves. AB - The frequency of unused surgeons' gloves with perforations was investigated by using a watertightness test. Lot-to-lot variations and inter-lot variation were found. It is the responsibility of the manufacturer to ensure that the quality of the lot is in accordance with the stated Acceptable Quality Level. PMID- 2895143 TI - Salmonellosis in a psychogeriatric ward: problems of infection control. PMID- 2895144 TI - An outbreak of Campylobacter jejuni infection in a neonatal intensive care unit. PMID- 2895145 TI - Postoperative skin-flap decongestion, leeches and Aeromonas hydrophila. PMID- 2895146 TI - Mycobacterial cross-contamination of bronchoscopy specimens. PMID- 2895147 TI - Household bleaches and HIV. PMID- 2895148 TI - The economics of sepsis control. PMID- 2895149 TI - Identification of a CD2- CD3+ T cell receptor-gamma+ peripheral blood lymphocyte subpopulation. AB - We have identified, in a healthy individual, a sub-population of human peripheral lymphocytes which surface express a CD3-TCR-gamma complex recognized by anti-Ti gamma A mAb, while being unreactive with a phycoerythrin-conjugated anti-CD2 antibody with T11/1 specificity. Further immunofluorescence analyses performed on uncultured cells indicated that such a putative CD2-CD3+ phenotype was restricted to a fraction of those T lymphocytes which carry a surface receptor of the "second family" (gamma/delta). The actual lack of CD2 expression was confirmed by a subsequent series of cloning experiments which showed that none of the three well characterized CD2 epitopic clusters, namely T11/1, T11/2, and T11/3, were detectable on the surface of the relevant cells. The cultured CD2-, CD3+/TCR gamma + lymphocytes were found to display, as well as their CD2+ counterparts, both non-MHC-restricted cytotoxic function and proliferative responses induced via the gamma receptor complex. In contrast, the proliferative capacity of the CD2-, CD3+/TCR-gamma + cells observed in a culture system designed for in vitro expansion of lymphocytes with undefined specificity was extremely limited. This may relate to an impaired interaction of the CD2- cloned lymphocytes with lymphocyte function-associated (LFA)3+ irradiated cells present in the feeder layer. Further characterization of such minor CD2- T lymphocytes subsets may help to better understand the biologic relevance of the CD2/LFA3 pathway of cell-cell interaction. PMID- 2895150 TI - 2H1--a novel antigen involved in T lymphocyte triggering. AB - A mAb anti-2H1, was produced against PHA-activated T cells from a lower primate, Aotus trivirgatus. Anti-2H1 reacted with 90% of peripheral T cells but was found to react with only 10% of thymocytes and some, but not all, leukemic T cell lines. 2H1 expression was dramatically increased when thymic cells were activated by Con A plus PMA. In contrast, anti-2H1 did not react with B cells, macrophages, null cells, or hematopoietic stem cell lines. More importantly, anti-2H1 antibody can induce T cell activation and proliferation in synergy with PMA or anti T11(3). SDS-PAGE analysis of polypeptides immunoprecipitated with anti-2H1 showed two major polypeptides of 140 and 105 kDa. Thus, the 2H1 Ag can be distinguished from T3, T11, and 9.3 Ag. These results indicate that the 2H1 Ag appears to be involved in the activation of T lymphocytes. PMID- 2895151 TI - Aerobactin-mediated uptake of iron by strains of Escherichia coli causing acute pyelonephritis and bacteraemia. AB - A total of 285 strains of Escherichia coli isolated from children and women with acute non-obstructive pyelonephritis and from patients with bacteraemia as well as 120 faecal strains of E. coli from healthy children and adults were examined for aerobactin-mediated uptake of iron. The incidence of aerobactin-positive strains was significantly more in isolates from children with acute pyelonephritis (81%) than in faecal isolates from healthy children (50%, P less than 0.01). It was also higher in isolates of E. coli from women with acute pyelonephritis (72%) compared with faecal isolates from healthy adults (42%, P less than 0.001). Of the E. coli strains causing bacteraemia, 55% were aerobactin positive. A significant correlation was found between the presence of aerobactin and expression of P-fimbriae in strains of E. coli isolated from children with acute pyelonephritis (P less than 0.01) and in isolates from bacteraemic patients (P less than 0.001). These results indicate that the presence of an aerobactin mediated system of iron uptake may be an important virulence factor in strains of E. coli that cause ascending pyelonephritis. PMID- 2895152 TI - Localization and in vivo activity of epidermal transglutaminase. AB - The plasma membrane-associated transglutaminase is responsible for the formation of a cornified envelope during terminal differentiation of epidermal keratinocytes. We have studied the epidermal distribution of this enzyme ("epidermal transglutaminase") and its activity by fluorescence microscopy in histological sections of normal human skin and human skin grafted onto nude mice. Three different techniques were employed: (i) incubation of skin sections with a monoclonal antibody raised against a purified preparation of the enzyme; (ii) incubation of skin sections with dansylcadaverine, a fluorescent substrate of the enzyme, in the presence of Ca++ ions; and (iii) subcutaneous injection of dansylcadaverine into mice, at least 2 months after grafting. The first technique is supposed to detect all enzyme molecules carrying the epitope that is recognized by the antibody, even when the enzyme is catalytically not active; the second should decorate all sites in which membrane-bound transglutaminase activity is located, and the third detects only sites in which transglutaminase is active in vivo. With the first two techniques a broad band of plasma membrane associated fluorescence, reaching from the middle of the spinous layer to the stratum corneum, was detected in both normal and grafted skin. In vivo enzyme activity, however, was found to be restricted to one, or at most two, cell layers at the interface of the stratum granulosum and stratum corneum and to coincide with the layer in which the antigenicity of involucrin, a natural substrate of epidermal transglutaminase, disappeared. PMID- 2895153 TI - Gamma glutamyl peptidase: a novel enzyme from hairless mouse epidermis. AB - Recent literature has suggested that pyroglutamate (PCA) formation in stratum corneum occurs by spontaneous cyclization of glutamine residues derived from filaggrin breakdown. This paper describes an enzymatic alternative. Epidermal homogenates from hairless mice were found to catalyze the formation of PCA from both glutamine and glutamic acid at pH 6.2. Enzyme activity responsible for the first step in this reaction, gamma-glutamyl peptide formation, was partially purified using ammonium sulfate precipitation followed by ion exchange, gel filtration, and hydroxylapatite chromatography. Enzyme preparations free of gamma glutamyl cyclotransferase activity (which forms PCA from certain gamma-glutamyl peptides) catalyzed formation of gamma-glutamyl-glutamine from glutamine and gamma-glutamyl-glutamate from glutamic acid. Enzyme preparations catalyzed hydrolysis of a variety of gamma-glutamyl peptides but did not split non-gamma glutamyl peptides or the transpeptidase substrate gamma-glutamyl-rho nitroanilide. Ammonium sulfate fractions containing both gamma-glutamyl peptidase and gamma-glutamyl cyclotransferase activity catalyzed linear formation of PCA from glutamic acid for periods of up to 19 h. Using gamma-glutamyl-leucine as a substrate, gamma-glutamyl peptidase activity was found to be much higher in crude extracts from epidermis than in preparations from liver, kidney, spleen, intestine, lung, brain, or heart. This activity has not, to our knowledge, been previously described in mammalian tissues. PMID- 2895154 TI - Modulating the beta-receptor in congestive heart failure. PMID- 2895156 TI - Psychopharmacologic treatment: a note on classroom effects. PMID- 2895155 TI - Neurohumoral profile in congestive heart failure: response to beta-blockade. AB - Beta-blockade has been reported to have beneficial hemodynamic effects in chronic congestive heart failure that may be related to alterations in the abnormal neurohumoral profile characteristic of this population. To determine the relationship of the neurohumoral profile to the hemodynamic response to beta blockade in patients with chronic congestive heart failure, neurohumoral and hemodynamic variables were measured in 10 subjects having congestive cardiomyopathy at baseline and after administration of the beta-blocker pindolol. Baseline stroke index was noted to have an inverse curvilinear relation with plasma norepinephrine (r = -0.69) and renin (r = -0.71) concentration. Pulmonary vascular resistance demonstrated a direct logarithmic relation with plasma norepinephrine concentration (r = 0.68). Increases in norepinephrine, dopamine, and epinephrine concentrations after dosing were noted, with the most marked increase in norepinephrine concentration being coincident with a significant decline in stroke volume index. Two patients not tolerating beta-blockade were characterized by having baseline norepinephrine concentrations 3 SD higher than those of the remaining patients, more marked increases in epinephrine concentration after dosing, and the most profoundly decompensated heart failure at baseline, as defined by the relationship between neurohumoral and hemodynamic variables. These observations suggest that increases in catecholamines after dosing reflect a compensatory response to the adverse hemodynamic-inotropic effects of beta-blockade in congestive heart failure. The neurohumoral profile and the relationship of neuroendocrine to hemodynamic parameters may be useful in delineating patients at risk for adverse hemodynamic effects of beta-blockade. PMID- 2895157 TI - Endocrine manipulation of animal growth. PMID- 2895158 TI - Effects of passive immunization with antisomatostatin serum on plasma corticosterone concentrations in young domestic cockerels. AB - Young cockerels (6-8 weeks old) were injected with serum from sheep immunized against somatostatin-14 (anti-SRIF) or normal sheep serum (NSS). Blood samples were withdrawn periodically for the determination of plasma corticosterone concentration by radioimmunoassay. With frequent (every 10 min) sampling, NSS treated control animals exhibited increased plasma corticosterone levels, presumably as a stress response to the experimental manipulation. Anti-SRIF stimulated a much greater increase in plasma corticosterone concentrations and a peak response was observed within 10 to 20 min, when the plasma corticosterone level reached more than twice that of the corresponding control value. With less frequent sampling, plasma corticosterone increased with anti-SRIF administration to as much as nine times the corresponding control value, and the peak response occurred much later. Under pentobarbitone anaesthesia, which itself increased basal corticosterone concentrations, anti-SRIF treatment promoted further increases in plasma corticosterone levels although to a smaller magnitude compared with conscious birds. The results suggest that endogenous somatostatin may play a role in the regulation of adrenocortical function in the domestic fowl. The mechanism of response may involve a central component. PMID- 2895159 TI - Calcitonin inhibition of prolactin secretion in isolated rat pituitary cells. AB - Salmon calcitonin inhibited TRH-stimulated release of prolactin in isolated pituitary cells from untreated female rats. These cells were still capable of responding to the fresh addition of TRH after the removal of calcitonin. Calcitonin gene-related peptide had only a weak effect in inhibiting prolactin release in these cells. Pituitary cells isolated from female rats which had been treated with weekly s.c. injections of 1 mg oestradiol dipropionate for 4 weeks, exhibited a marked increase in the magnitude of the inhibition of prolactin release by salmon calcitonin. Both basal and TRH-stimulated release of prolactin were inhibited by concentrations of 0.1 nmol salmon calcitonin/l or higher. Prolactin release from these cells was also inhibited at somewhat higher concentrations by calcitonin gene-related peptide. Our results demonstrate that calcitonin can directly inhibit basal as well as TRH-stimulated prolactin release by acting directly at the pituitary. The results strongly suggest that the peptide may be involved in the regulation of prolactin release in certain physiological conditions. PMID- 2895160 TI - Comparison of peptide release from fetal rat hypothalamic neurones cultured in defined media and serum-containing media. AB - Primary cultures of rat hypothalamic neurones were maintained either in a serum supplemented medium or in a serum-free chemically defined medium for up to 6 weeks. The release of the 41 amino acid-containing peptide, corticotrophin releasing factor (CRF-41), vasopressin (AVP) and somatostatin (SRIF) were followed using immunoassays. In response to K+ (56 mmol/l) depolarization both the quantities of peptides released and the magnitude of responses were significantly greater from cultures maintained in the fully supplemented defined medium. As a consequence, release of CRF-41 and AVP could be measured directly, without requiring the concentration step necessary for cultures grown in serum. The response to K+ depolarization increased with the age of the culture, suggesting neuronal maturation. Responses to K+ depolarization were Ca2+ dependent, and the addition of corticosterone (100 nmol/l) to the defined medium caused a significant reduction in the response of neurones secreting CRF-41 and AVP, but not those secreting SRIF, to depolarization. This suggests the retention in vitro of the responsiveness of stress-associated neuropeptides to the negative feedback effects of corticosterone. Neurones producing CRF-41 and AVP responded significantly in a dose-dependent manner to acetylcholine stimulation, whereas those producing SRIF did not. As cultures matured, the CRF-41- and AVP-producing neurones became more sensitive to acetylcholine with the maximal response at 1 nmol acetylcholine/l. In conclusion, the culture of rat hypothalamic neurones is improved in terms of peptide output when the cultures are maintained in a defined medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2895161 TI - Urinary excretion of D-glucaric acid in porphyria cutanea tarda. AB - Twenty patients with porphyria cutanea tarda who had ingested no alcohol for at least 10 days before sampling were found to possess urinary D-glucaric acid levels similar to those of 30 clinically healthy controls. Correlation between urinary excretion of D-glucaric acid on the one hand and plasma or urinary porphyrin concentrations on the other was not statistically significant. These results suggest that the high urinary concentrations of D-glucaric acid found in porphyria cutanea tarda patients by Budillon et al. (Acta Hepato-Gastroenterol. 25 (1978) 267) may have been due to recent consumption of alcohol rather than to the porphyrin pathology. PMID- 2895162 TI - Enzymological features of aromatic amino acid biosynthesis reflect the phylogeny of mycoplasmas. AB - Acholeplasma laidlawii possesses a biochemical pathway for tyrosine and phenylalanine biosynthesis, while Mycoplasma iowae and Mycoplasma gallinarum do not. The detection of 7-phospho-2-dehydro-3-deoxy-D-arabino-heptonate (DAHP) synthase (EC 4.1.2.15), dehydro-shikimate reductase (EC 1.1.1.25) and 3-enol pyruvoylshikimate-5-phosphate synthase (EC 2.5.1.19) activities in cell-free extracts established the presence in A. laidlawii of a functional shikimate pathway. L-Phenylalanine synthesis occurs solely through the phenylpyruvate route via prephenate dehydratase (EC 4.2.1.51), no arogenate dehydratase activity being found. Although arogenate dehydrogenase was detected, L-tyrosine synthesis appears to occur mainly through the 4-hydroxyphenylpyruvate route, via prephenate dehydrogenase (EC 1.3.1.12), which utilized NAD+ as a preferred coenzyme substrate. L-Tyrosine was found to be the key regulatory molecule governing aromatic biosynthesis. DAHP synthase was feedback inhibited by L-tyrosine, but not by L-phenylalanine or L-tryptophan; L-tyrosine was a potent feedback inhibitor of prephenate dehydrogenase and an allosteric activator of prephenate dehydratase. Chorismate mutase (EC 5.4.99.5) was sensitive to product inhibition by prephenate. Prephenate dehydratase was feedback inhibited by L-phenylalanine. It was also activated by hydrophobic amino acids (L-valine, L-isoleucine and L methionine), similar to results previously found in a number of other genera that share the Gram-positive line of phylogenetic descent. Aromatic-pathway-encoded cistrons present in saprophytic large-genome mycoplasmas may have been eliminated in the parasitic small-genome mycoplasmas. PMID- 2895163 TI - Detection of prion protein mRNA in normal and scrapie-infected tissues and cell lines. AB - Prion protein (PrP) forms the fibrils or prion rods isolated from scrapie infected brain and has been proposed as the major component of the infectious agent of this slowly progressive spongiform encephalopathy. In previous Northern blot analyses PrP-specific mRNAs have been found in both normal and scrapie infected brains but not in spleen, an organ which harbours large titres of infectivity. In the present study, mouse PrP DNA was used to probe for PrP mRNA in assorted tissues and cells. A reexamination of mouse and hamster spleens revealed that they contained low levels of PrP mRNA (approx. 0.8% of that in brain mRNA). No consistent differences were observed between normal and scrapie infected tissues. Also positive for PrP mRNA under stringent hybridization conditions were mouse epithelial, neuroblastoma, erythroid, B-lymphocytic and embryo fibroblast tissue culture cell lines, a hamster ovary cell line, a rat glioma cell line, and human T lymphocytic and neuroblastoma cell lines. In contrast, no PrP mRNA was detected in two mouse myeloid cell lines and one T cell lymphoma. These results provide evidence that PrP is a protein common to numerous, but not all, cell types besides those of the brain. PMID- 2895164 TI - Recurrence of neuroleptic malignant syndrome. AB - Presumptive risk factors for recurrence of neuroleptic malignant syndrome (NMS) and clinical evidence for its pathogenesis are discussed. All earlier reports describing patients who have had NMS and who were either safely restarted on neuroleptic or who developed recurrence are reviewed. The authors also present their own experiences with both outcomes. Possible risk factors for recurrent NMS are administration of high-potency neuroleptics and reintroduction of neuroleptics before the initial episode of NMS has completely resolved. Bipolar disorder and concomitant use of lithium may predispose to NMS and therefore could also heighten the risk of recurrence. PMID- 2895165 TI - Marine soft corals of the genus Pseudopterogorgia: a resource for novel anti inflammatory diterpenoids. AB - This paper is a brief review of the diterpenoid chemistry of gorgonian corals of the genus Pseudopterogorgia. Previously described compounds and several new diterpenoids are presented in the context of their potential utilization in the development of anti-inflammatory and analgesic drugs. PMID- 2895166 TI - Isolation of caffeine from the gorgonian Paramuricea chamaeleon. PMID- 2895167 TI - Excitation of area postrema neurons by transmitters, peptides, and cyclic nucleotides. AB - 1. Multiple-barreled microelectrodes were used to record from neurons in the area postrema of anesthetized dogs and to test the responses of the neurons to a variety of substances in this structure, which is known to function as the chemoceptive trigger zone for emesis. 2. The neurons in area postrema were silent at rest but could be "found" by virtue of their response to ionophoretic glutamate. The glutamic response was brief and of short latency with high frequency of discharge. 3. Dog area postrema neurons were also excited by over 20 other substances, including acetylcholine, the biogenic amines, several peptides, and at least two hormones. Not all agents were excitatory, however. 4. The responses to all excitatory agents except glutamate were similar and unusual. All responses showed a relatively long latency (3-20 s), a long duration of excitation (30 s to many minutes), and a low discharge frequency (1-3 Hz). 5. There was a good correlation between substances that were excitatory on area postrema neurons and substances known to cause emesis. Because emesis due to intravenous application of these substances is known to be abolished in animals with ablation of the area postrema, it is very likely that recordings were from the neurons which trigger the response. 6. Because so many substances elicit the same type of response there is a possibility that all utilize a common second messenger. Neurons were not excited by ionophoresis of guanosine 3',5'-cyclic monophosphate (cGMP) but were excited by 8-bromo-adenosine 3',5'-cyclic monophosphate (cAMP) and by forskolin, an activator of adenylate cyclase. 7. Behavioral studies were performed looking for emetic responses in awake dogs following intravenous injection of apomorphine, insulin, angiotensin II, and leucine enkephalin. For each a threshold concentration could be determined, which would consistently evoke emesis. 8. Dogs pretreated with phosphodiesterase inhibitors (theophylline, 3-isobutyl-1-methylxanthine, or RO 1724) showed a shift in the threshold concentration of the above substances that triggered emesis, such that emesis was evoked by lower concentrations than in the control. 9. These results suggest that neurons of the dog area postrema trigger the emetic reflex in response to specific receptors for a great variety of transmitters, peptides, and hormones, and that these receptors act through a common second messenger, cAMP. PMID- 2895168 TI - Pitfall of Sipple's syndrome diagnosis by 131I-metaiodobenzylguanidine (MIBG). PMID- 2895169 TI - Effects of biotin deficiency on serum fatty acid composition: evidence for abnormalities in humans. AB - In three patients who developed biotin deficiency during parenteral alimentation, serum fatty acid compositions of the four major lipid classes (phospholipid, cholesteryl ester, triglyceride and free fatty acid) were measured. Relative to the normal range, percent compositions of an odd-chain fatty acid (either 15:0 or 17:0 or both) were increased in each class of lipid, and these abnormalities generally returned to normal or decreased toward normal with biotin therapy. Abnormalities in particular fatty acids in the omega 6, omega 3 and omega 9 pathways were also found, but these abnormalities did not resolve with biotin therapy. These data provide evidence in favor of the conclusion that biotin deficiency causes increases in the composition of some odd-chain fatty acids in humans, perhaps by the same mechanism that leads to odd-chain fatty acidemia in the inborn deficiency of the biotin-dependent enzyme propionyl-CoA carboxylase. PMID- 2895170 TI - Ouabain-induced elevation in forearm vascular resistance, calcium entry and alpha adrenoceptor blockade, and release and removal of noradrenaline. AB - The activity of the ouabain-sensitive Na+K+-ATPase may be reduced in primary hypertension by an ouabain-like humoral factor with resultant increase in intracellular Na+ and Ca2+ and peripheral vasoconstriction. To test this, we studied the forearm blood flow in 18 normotensive subjects. First, nifedipine, phentolamine, prazosin, sodium nitroprusside and ouabain were infused into the brachial artery. Secondly, each vasodilator was given in combination with ouabain. Blood pressure was measured directly, and blood flow by venous occlusion plethysmography. When nifedipine was combined with ouabain the elevation of vascular resistance was completely abolished. We detected no effect on the forearm veno-arterial difference for noradrenaline following intra-arterial infusion of drugs. If an ouabain-like factor plays a role in producing the elevated resistance of chronic hypertension, calcium entry blockers will act close to the site of this primary abnormality. PMID- 2895171 TI - STOP-Hypertension--preliminary communication from the pilot study of the Swedish Trial in Old Patients with Hypertension. AB - The Swedish trial in old patients with hypertension (STOP-Hypertension) is a multicentre, randomized, double-blind study of beta-blockers/diuretics versus placebo in old hypertensives. Primary end-points are stroke and myocardial infarction (fatal and non-fatal) as well as other cardiovascular mortality. To evaluate the logistics of STOP-Hypertension, a pilot study was carried out. All patients aged 70-84 years in 31 centres were consecutively registered in a log book. Altogether 4668 patients were screened: 41.5% had previously been treated for hypertension and 13.5% had blood pressures greater than or equal to 180/105 mmHg. Thus, 55% were 'hypertensive'. In all, 465 patients (18% of the 'hypertensive' patients) started a 3-month washout period (previously treated, n = 396) or a 4-week run-in period (previously untreated, n = 69) period. The most frequent reasons for not starting the run-in/washout were other indications for treatment with beta-blockers/diuretics (13%), unwillingness to participate (8%) or isolated systolic hypertension (4%). The pilot study was evaluated after 1 year: 89 patients (1.9%) had been randomized, 66 patients (1.4%) were still in the run-in/washout period and the majority of the remaining patients were not randomized because they had not reached the inclusion blood pressure (greater than or equal to 180 mmHg systolic and/or greater than or equal to 105 mmHg diastolic) following withdrawal of their antihypertensive medication. During the run-in/washout period there were few serious clinical events: one case of myocardial infarction, three patients had strokes (two fatal), 10 developed congestive heart failure, three tachyarrhythmia and two pneumonia (one fatal).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2895172 TI - Serum aspartate aminotransferase levels after rotavirus gastroenteritis. PMID- 2895173 TI - Beneficial effects of early hypocaloric enteral feeding on neonatal gastrointestinal function: preliminary report of a randomized trial. AB - In a prospective randomized trial, we studied the effects of early hypocaloric enteral feedings (PO) begun at 48 hours of age in 19 infants compared with 20 infants who received no enteral feedings (NPO) for at least the first 9 days of life. Both groups initially received the majority of their calories by parenteral alimentation. The groups were similar with respect to birth weight, gestational age, sex, Apgar score, and major neonatal diagnoses. The early enteral feeds proved to be significantly beneficial without an increased incidence of complications. The PO group reached full enteral feedings faster than the NPO group (31.2 vs 47.3 days). The PO group had a greater decline in serum bilirubin concentration over the first 2 weeks of life and spent less time under phototherapy (6.8 vs 9.5 days). Less cholestasis was observed among the PO infants (6.7% vs 33%), and peak direct bilirubin levels were also lower (0.7 vs 2.5 mg/dL). Osteopenia of prematurity, manifested by significantly lower alkaline phosphatase activity, was also decreased in the PO group, perhaps because of greater calcium intake during the first month among PO infants (1.3 vs 0.8 g). Compared with complete bowel rest, early onset of hypocaloric enteral feedings has beneficial effects on indirect hyperbilirubinemia, cholestatic jaundice, and metabolic bone disease of very low birth weight infants. PMID- 2895174 TI - Intestinal enzyme profiles in normal and rotavirus-infected mice. AB - To investigate further the pathophysiology of rotavirus-induced diarrhea, changes in specific activities of eight relevant intestinal enzymes [alkaline phosphatase, thymidine kinase, lactase, maltase, sucrase, Na+,K+-adenosine triphosphatase (ATPase), adenylate and guanylate cyclases] were measured following infection of suckling mice with murine rotavirus (epizootic diarrhea of infant mouse strain) and compared with age-matched control mice. The concentration of lactose within the lumen of the gastrointestinal tract during infection was also measured. During the course of infection, activities of alkaline phosphatase and lactase decreased, whilst the activity of thymidine kinase increased. Precocious maturation profiles of sucrase and maltase enzymes were observed. No significant changes were detected in the activities of Na+,K+ ATPase or the adenylate and guanylate cyclases. These results are discussed in relation to existing and novel hypotheses on the pathogenesis of rotavirus induced diarrhea. PMID- 2895175 TI - Selective cell transplantation using bioabsorbable artificial polymers as matrices. AB - To date, selective cell transplantation has involved injecting cell suspensions into tissues or the vascular system. This study describes attaching cell preparations to bioerodable artificial polymers in cell culture and then implanting this polymer-cell scaffold into animals. Using standard techniques of cell harvest, single cells and clusters of fetal and adult rat and mouse hepatocytes, pancreatic islet cells, and small intestinal cells have been seeded onto biodegradable polymers of polyglactin 910, polyanhydrides, and polyorthoester. Sixty-five fetuses and 14 adult animals served as donors. One hundred fifteen polymer scaffolds were implanted into 70 recipient animals: 66 seeded with hepatocytes; 23 with intestinal cells and clusters; and 26 with pancreatic islet preparations. The cells remained viable in culture, and in the case of fetal intestine and fetal hepatocytes, appeared to proliferate while on the polymer. After four days in culture, the cell-polymer scaffolds were implanted into host animals, either in the omentum, the interscapular fat pad, or the mesentery. In three cases of fetal intestinal implantation coupled with partial hepatectomy, successful engraftment occurred in the omentum, one forming a visible 6.0 mm cyst. Three cases of hepatocyte implantation, one using adult cells and two using fetal cells, have also engrafted, showing viability of hepatocytes, mitotic figures, and vascularization of the cell mass. To date, no pancreatic islets have survived implantation. This method of cell transplantation, which we have termed "chimeric neomorphogenesis," is an alternative to current methods and requires further study. PMID- 2895176 TI - Changes in renal sympathetic nerve activity, heart rate and arterial blood pressure associated with eating in cats. AB - 1. Renal sympathetic nerve activity, heart rate and arterial blood pressure were simultaneously measured in thirteen awake cats before, during and after eating which was evoked by presenting food for a period of 10-15 s. 2. With food presentation, eating behaviour occurred in 93% (191) of 205 trials, and renal sympathetic nerve activity significantly increased in 65% of the 191 trials. On the other hand, in many of food presentation trials when no eating occurred, or with presentation of an empty food box, renal sympathetic nerve activity did not change significantly. 3. Eating started 1-8 s after the food presentation. The increase in renal sympathetic nerve activity was closely related to the beginning of eating but not to the onset of food presentation. Renal sympathetic nerve activity and heart rate increased with a slight time lag of 0.5-1.5 s from the onset of eating, whereas an increase in arterial blood pressure followed the onset of eating by 5.5 s. After the beginning of eating, renal sympathetic nerve activity, heart rate and arterial blood pressure increased at a maximum of 61 +/- 18% (mean +/- S.E. of mean), 26 +/- 4.0 beats/min, and 17 +/- 4.9 mmHg from the control values at 1.0, 5.5 and 11.5 s, respectively. 4. Cardiac-related grouped discharges of renal sympathetic nerve activity, which were observed at rest, increased during eating. 5. When arterial blood pressure was elevated by noradrenaline (2-5 micrograms/kg I.V.), renal sympathetic nerve activity during resting was almost completely inhibited and the increase in renal sympathetic nerve activity during eating was not induced. 6. We conclude that renal sympathetic nerve activity increases in association with eating behaviour but not as firmly with the food presentation, and that the increase in renal sympathetic nerve activity is initiated by descending input from the higher central nervous system rather than either by the viscero-autonomic reflex due to food intake or by the baroreflex due to a decrease in arterial blood pressure. PMID- 2895177 TI - Intracellular recordings from myenteric neurones in the human colon. AB - 1. Intracellular recordings were made from cells in the myenteric plexus of the human colon in freshly dissected tissue obtained from patients undergoing surgery for the removal of carcinomas or diverticular bowel. 2. Twenty-seven cells from ten preparations were classified as neurones and had overshooting action potentials, an average resting potential of -54 +/- 9 mV, an average input impedance of 1.05 +/- 0.59 x 10(8) omega and a variety of synaptic inputs. 3. Twenty-three (out of twenty-five neurones tested) received nicotinic fast excitatory synaptic inputs (fast e.p.s.p.s) that were blocked reversibly by hexamethonium and mimicked by acetylcholine. These nerve cells bore a close resemblance to S cells that have been characterized in the guinea-pig small-bowel myenteric plexus. 4. One cell had a long after-hyperpolarization following its impulses and was similar to AH cells in the guinea-pig small bowel. 5. Three neurones received inhibitory synaptic inputs, up to 15 mV in amplitude, lasting up to 10 s, associated with a decrease in input impedance and with a reversal potential between -80 and -90 mV. 6. Slow excitatory synaptic potentials were only detected in the single AH cell. The slow e.p.s.p. was associated with a depolarization of up to 12 mV, an increase in excitability and an increase in the input impedance of the neurone. 7. The proportion of S and AH cells differ considerably from that reported in the guinea-pig small-bowel preparation. Possible causes of the differences are discussed. PMID- 2895178 TI - Excitatory amino acid receptors and synaptic transmission in the rat ventrobasal thalamus. AB - 1. Extracellular single-neurone recordings were made in the ventrobasal thalamus (v.b.t.) of urethane-anaesthetized rats with multi-barrel ionophoretic electrodes in order to test the hypothesis that excitatory amino acid receptors are involved in the responses of these neurones to stimulation of sensory afferents. 2. Responses of neurones to either physiological stimulation of hair and vibrissa follicle sensory afferents and to ionophoretically applied excitatory amino acids were challenged with the antagonists D-2-amino-5-phosphonovalerate (APV), kynurenate and gamma-D-glutamylaminomethyl sulphonate (GAMS). 3. In agreement with previous findings in other brain areas, ionophoretically applied APV was found to selectively antagonize responses of v.b.t. neurones to N-methylaspartate (NMA), whereas GAMS was found to be moderately kainate selective. Kynurenate was found to be relatively non-selective. 4. Responses of neurones to short-duration (10-20 ms) physiological stimulation of afferents were resistant to APV when this antagonist was applied with NMA-selective ionophoretic currents. In contrast, these APV currents were adequate to antagonize responses to maintained physiological stimulation. 5. The broad spectrum excitatory amino acid antagonist kynurenate was found to block synaptic responses of v.b.t. neurones to both short duration and maintained stimuli when it was applied with currents which were sufficient to reduce responses to ionophoretic quisqualate. 6. GAMS was found to selectively block kainate responses in a proportion of the neurones tested. In such cases, there was little effect of the antagonist on the responses evoked by either short-duration or maintained sensory stimuli. 7. It is concluded that excitatory amino acid receptors of both the NMDA and non-NMDA type are involved in the synaptic responses of v.b.t. neurones to sensory afferent stimulation, and that the apparent synaptic pharmacology depends on the mode of stimulation of the afferent pathway. PMID- 2895180 TI - Release of octopamine by Leydig cells in the central nervous system of the leech Macrobdella decora, and its possible neurohormonal role. AB - 1. The release of octopamine by the central nervous system of the leech Macrobdella decora was examined. Isolated ganglia or chains of ganglia were incubated in salines of varying composition, and the release of octopamine into the perfusate was measured using a radioenzymatic method. In some experiments this release was correlated with the electrical activity of the octopamine containing Leydig cells, as measured via a microelectrode in the cell body. 2. Chains of ganglia incubated in normal saline released 0.04 pmol octopamine/ganglion/3 min incubation period. This amount was not significantly increased by either the monoamine oxidase inhibitor iproniazid phosphate (0.1 mM) or the uptake inhibitor desipramine (10 microM) alone, but was by both together. Nominally calcium-free saline containing 20 mM Mg++ significantly decreased octopamine release. 3. High K+ saline increased octopamine release significantly in both standard saline and one containing the blocking agents. This increase was sevenfold in saline containing iproniazid phosphate and desipramine, and was significantly greater than that obtained in saline without the blockers. This provides further evidence for the role of octopamine as a neuroactive substance in the leech by indicating the existence of possible mechanisms for its uptake and/or inactivation. 4. Octopamine release was positively correlated with the firing frequency of Leydig cells. No release was detectable when the cells were prevented from firing by the injection of hyperpolarizing current. Release was frequency-dependent when the cells fired at frequencies of 0.1-1.0 spikes/s. Elevating the external calcium concentration from 1.8 to 5.4 mM significantly increased octopamine release at all frequencies tested, except for 0 spikes/s, at which release remained below detectabilty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2895181 TI - CT scan and surgery in subdural empyema: a case report. AB - A high index of suspicion is required to pick up cases of subdural empyema in clinical practice. CT scan may be normal in the initial stages. Early neurosurgical intervention is desirable to reduce mortality and morbidity in this condition. PMID- 2895179 TI - Vasopressin, oxytocin, dynorphin, enkephalin and corticotrophin-releasing factor mRNA stimulation in the rat. AB - 1. Cryostat sections were cut through the hypothalamus of rats which had been given a 2% (w/v) NaCl solution to drink for up to 12 days. 2. In situ hybridization histochemistry was performed on these sections using synthetic oligonucleotide probes against part of the precursor sequence for vasopressin, oxytocin, dynorphin, enkephalin and corticotrophin-releasing factor (CRF). 3. Drinking 2% NaCl solution resulted in a progressive increase of vasopressin, oxytocin and dynorphin mRNAs hybridized in the magnocellular neurones of the supraoptic (s.o.) and paraventricular (p.v.) nuclei. No enkephalin mRNA was detected in the magnocellular areas of the control animals although small quantities of probe did hybridize after 12 days of salt loading and after the stress of I.P. hypertonic saline. 4. Ten-day-lactating female rats were also studied. They had a very marked increase in oxytocin mRNA with smaller increases of vasopressin and dynorphin mRNAs. No detectable enkephalin mRNA was hybridized in the magnocellular s.o. or p.v. nuclei and CRF mRNA was unchanged in both the s.o. nucleus and the p.v. nucleus. PMID- 2895182 TI - CT scan and surgery in subdural empyema. PMID- 2895183 TI - Activity of arylsulfatase A, B-glucosidase and hexosaminidases in chorionic villi at six, eight and ten weeks' gestational age. AB - Chorionic villus sampling is becoming an accepted method of prenatally diagnosing metabolic diseases. There are few published data on sampling at various gestational ages. Different investigators, using different methods of chorionic biopsy, perform the sampling at various gestational ages. Accurate interpretation of results is dependent on reliable normal values, which could differ on the basis of gestational age. The enzymatic activities of arylsulfatase A, B glucosidase and hexosaminidases were compared in trophoblast from six-, eight- and ten-week gestations. No significant differences in activity levels were detected. This finding confirms the accuracy of metabolic diagnosis for these enzyme-deficiency syndromes in trophoblastic tissue at gestational ages of six to ten weeks without a requirement for gestational-age-specific normal values. PMID- 2895184 TI - Cutaneous polyarteritis nodosa and thromboses of the superior and inferior venae cavae. AB - The case of an adolescent female with cutaneous polyarteritis nodosa and thromboses of the superior and inferior venae cavae is presented. Although thromboses of major vessels have been well described in systemic lupus erythematosus and Behcet's disease, this is only the second case of thromboses of major vessels in association with cutaneous polyarteritis nodosa. Possible pathophysiologic mechanisms are discussed. PMID- 2895185 TI - Mitochondrial DNA variation among geographical populations of the screwworm fly, Cochliomyia hominivorax. PMID- 2895186 TI - Hosts of mosquitoes in the coastal plain of North Carolina. PMID- 2895187 TI - Service experience using DNA analysis for genetic prediction in Duchenne muscular dystrophy. AB - In August 1985 we instituted a carrier and prenatal testing service for Duchenne muscular dystrophy (DMD) using direct DNA analysis. The experience over the first nine months is described. We have analysed samples for RFLPs from 154 people including 53 women at risk of being DMD carriers from 37 families. We used the probes pERT87.8 (BstXI and TaqI polymorphisms), 87-15 (TaqI polymorphism), and pXJ1.1 (TaqI polymorphism). Forty-one of the women have had their risks altered. We found one deletion (pERT87-8) out of 23 DNA samples analysed from affected boys. We used a recombination fraction of 0.05 in risk calculations but did not detect any known crossovers. In nine of the families there is only an isolated case of DMD. In families where we have not been able to alter the risk of the women being a carrier (for example, because all brothers are dead), we have offered prenatal exclusion and have carried out one first trimester prenatal diagnosis on this basis. Lowering the risk of an affected fetus to less than 2.5% appears to be a satisfactory situation for many (most) of the women involved and seems to justify the introduction of genetic prediction based on single intragenic probes despite the 5% recombination frequency. PMID- 2895188 TI - The use of restriction fragment length polymorphisms in prenatal diagnosis of dihydropteridine reductase deficiency. AB - Using a human dihydropteridine reductase (hDHPR) cDNA probe we have detected two AvaII and one MspI restriction fragment length polymorphisms (RFLPs). We show that these RFLPs are in disequilibrium and calculate that approximately 60% of Caucasians are heterozygous for at least one RFLP. We demonstrate the usefulness of these RFLPs in prenatal diagnosis of DHPR deficiency in one family. This disorder can also be predicted by enzyme assays and we therefore discuss the relative merits of the two methods of prenatal diagnosis. PMID- 2895189 TI - Absence of close linkage between benign hereditary chorea and the locus D4S10 (probe G8). AB - A genetic linkage study between benign hereditary chorea and the locus D4S10 using the DNA probe G8 has shown two recombinations in five small families. There were negative lod scores at recombination fractions that show conclusive evidence of linkage in 16 larger British Huntington's disease families. We suggest that although benign hereditary chorea and Huntington's disease may have some clinical similarities they are probably at two different loci. PMID- 2895190 TI - Expression of the mdr (P-glycoprotein) gene in Chinese hamster digestive tracts. AB - P-glycoprotein has been shown to be responsible for multidrug resistance in mammalian cells. However, its physiological roles in normal cells are not known. The gene encoding this protein has been shown to express at a relatively high level in human digestive tracts. In the present study, in situ hybridizations were employed to determine the expression of this gene in gastrointestinal tissues. Epithelial cells in the villi of small intestine, colon, and stomach were rich in the P-glycoprotein gene transcript. Observations were consistent with the idea that the P-glycoprotein plays a role in detoxification by pumping potentially harmful compounds into the lumen of digestive tracts in animals. PMID- 2895191 TI - Renal vasoconstriction and transient declamp hypotension after infrarenal aortic occlusion: role of plasma purine degradation products. AB - To better understand renal and systemic hemodynamics associated with hindquarter ischemia produced by aortic compression, chloralose-anesthetized dogs were given phentolamine while an external clamp maintained infrarenal aortic pressure below 25 mm Hg for 45 minutes. In four sham-operated dogs, infrarenal pressure was maintained; reinforced cannulas, capable of resisting clamp compression, were placed within the aorta and the inferior vena cava. Suprarenal and infrarenal arterial pressure and renal blood flow were continuously monitored. Blood samples taken before clamp application and at 1, 3, 5, and 10 minutes after clamp removal were assayed for adenosine, inosine, xanthine, and hypoxanthine. On clamp removal suprarenal pressure immediately dropped from a preclamp pressure of 114 to 82 mm Hg but returned to preclamp values within 1 minute. Renal blood flow was significantly reduced after clamp release, reaching a nadir of 39% of preclamp flow. This reduction persisted despite a normalization of arterial pressure. Summed plasma purines were significantly elevated 1 minute after clamp removal. Sham-operated dogs showed no significant alterations in arterial pressure, renal blood flow, or plasma purine levels. This study demonstrates a significant non alpha-adrenergic receptor-mediated reduction in renal blood flow and a coincident increase in purine degradation products after removal of an infrarenal aortic cross-clamp. PMID- 2895192 TI - Adult T-cell leukemia/lymphoma in Brooklyn. AB - Fifteen patients with adult T-cell leukemia/lymphoma (ATLL) were identified in less than a two-year period in the Crown Heights-Bedford Stuyvesant section of Brooklyn, NY. All patients were black; nine patients originated from the Caribbean islands and six from the southern United States. Two of the patients were father and daughter, the first evidence of familial occurrence in the United States. Their clinical course was similar to that of previously described patients with this disorder. To our knowledge, these 15 patients represent the largest series of ATLL reported in the United States. We recommend that ATLL be seriously considered in the differential diagnosis of patients with non-Hodgkin's lymphoma, mycosis fungoides, lymphatic leukemia, or hypercalcemia. PMID- 2895193 TI - Treatment of the patient with rheumatoid arthritis refractory to standard therapy. PMID- 2895195 TI - [New hormone therapy. Somatostatin derivatives]. PMID- 2895194 TI - Effects of DJ-7141, a new alpha-2 agonist, 2-(2-chloro-6-fluorophenyl)-2,3,5,6 tetra-hydro-1H-imidazo[1,2-a] imidazole hydrochloride, on the isolated atrium, cross-perfused with blood from a support dog. AB - The effects of DJ-7141, a new alpha-2 agonist, on an isolated atrial preparation cross-perfused with arterial blood from a support dog were investigated. In the isolated atrium, a selective injection of DJ-7141 (1-100 micrograms) into the sinus node artery induced dose-dependent positive chronotropic and inotropic effects. The positive cardiac effects of DJ-7141 were not only inhibited by propranolol and by imipramine, but reversed to negative effects, whereas the positive cardiac effects of norepinephrine were blocked by propranolol and potentiated by imipramine. Tetrodotoxin (TTX) did not modify the cardiac responses to DJ-7141. After propranolol treatment, the negative chronotropic and inotropic responses to DJ-7141 were not influenced by atropine, which completely blocked acetylcholine-induced cardiac responses. When DJ-7141 was injected into the support dog at a dose of 10-300 micrograms/Kg i.v., it induced a brief increase in femoral arterial blood pressure and a long-lasting decrease in heart rate in the support dog and increases in atrial rate and contractile force in the isolated atrium. These results suggest that the new alpha-2 agonist, DJ-7141, induces indirect positive chronotropic and inotropic effects due to a tyramine like action and direct negative cardiac effects in the isolated dog heart, and that the tyramine-like effect may be partially responsible for the increase in blood pressure seen with DJ-7141 in in situ dogs. PMID- 2895196 TI - [Synthesis of peptide hormones by genetic engineering]. PMID- 2895197 TI - Concurrent adult T-cell leukemia and acute myeloblastic leukemia. AB - A 49-year-old man developed adult T-cell leukemia (ATL) and acute myeloblastic leukemia (AML) at the same time. Using Southern blotting analysis, the leukemic cells of the ATL were found to contain the human T-cell leukemia virus type I (HTLV-I) proviral genome, whereas those of the AML did not, indicating the HTLV-I not to be associated with the AML oncogenesis. At the initial presentation, the serum anti-HTLV-I antibody was judged on screening by a routine particle agglutination (PA) test and an indirect immunofluorescence assay (IF) to be negative. By Western blotting analysis, however, the serum was proved to be positive for anti-HTLV-I antibody. These results indicate that a routine PA-test and an IF may show false negative reactions on very rare occasions of low antibody titer. This is the first report of a coincidence of ATL with another type of leukemia. PMID- 2895198 TI - Adult T-cell leukemia by probable horizontal transmission from husband to wife. AB - A 60-year-old housewife was affected with adult T-cell leukemia (ATL) 10 years after her husband died of T-cell lymphoma, which was retrospectively diagnosed as ATL. She had never had a blood transfusion nor any indication of infection by human T-cell lymphotropic virus type I (HTLV-I) from her parents. The report suggested the wife to have developed ATL by horizontal transmission of HTLV-I from her husband 31 years after their marriage. PMID- 2895199 TI - [Immunological analysis on the results determined by the particle agglutination test and enzyme immunoassay of anti-ATLA]. PMID- 2895200 TI - [Impressions from the 21st congress of the ICM (International Confederation of Midwives)]. PMID- 2895201 TI - Pharmacological properties of SM-3997: a new anxioselective anxiolytic candidate. AB - Pharmacological properties of SM-3997 (3a alpha,4 beta,7 beta,7a alpha-hexahydro 2-(4-(4-(2-pyrimidinyl)-1- piperazinyl)-butyl)-4,7-methano-1H-isoindole-1,3(2H) dione dihydrogen citrate) have been examined in rats and mice. SM-3997 showed a dose-related anticonflict activity in rats in a water lick conflict paradigm, and it had no effect on water consumption in a spontaneous water drinking test. The potency of SM-3997 appeared to be equal to that of buspirone and about one-half that of diazepam. No tolerance to the anticonflict activity of SM-3997 was observed following 5 and 10 consecutive days of treatment. Unlike diazepam, SM 3997 had no anticonvulsant effect and had very weak muscle relaxant and hypnotic effects. On the other hand, SM-3997 and buspirone exhibited dopamine antagonistic action, although the potency of SM-3997 was less than one fourth that of buspirone. These results show that SM-3997 is a new anxioselective anxiolytic agent which is weaker than buspirone in the dopaminergic neuron system. PMID- 2895202 TI - Neurophysiological theory of intestinal motility. PMID- 2895203 TI - [Clinical studies on vesicoureteral reflux--significance of detection of the "missing VUR" (vesico-ureteral reflux)]. PMID- 2895204 TI - [Replacement of skin defects of the foot]. PMID- 2895205 TI - Sensitivity of the EMIT d.a.u. for benzodiazepines. PMID- 2895206 TI - A clinical study of series electro-acupuncture of 1000 cases of poliomyelitis sequelae. PMID- 2895207 TI - [Patients with increased liver enzyme levels--when and how are they to be examined?]. PMID- 2895208 TI - [Compartment syndrome after foot distortion]. PMID- 2895209 TI - [Treatment of pain in suspected acute myocardial infarction--current views on therapeutical alternatives]. PMID- 2895210 TI - [Intrapancreatic islet cell peptides and neuropeptides--a state of the art review]. PMID- 2895211 TI - Cadmium fume inhalation and emphysema. AB - Lung function and chest radiographs of 101 men who had worked for 1 or more years manufacturing copper-cadmium alloy were compared with those of a referent group matched for age, sex, and employment status. Cigarette consumption was similar in the two groups. The cadmium workers had an excess of abnormalities of lung function and of radiographic changes consistent with emphysema. Classification of the cadmium workers by exposure categories based on either estimated cumulative cadmium exposure or liver cadmium measured by neutron activation analysis showed that abnormalities of lung function were greatest in those with the highest cumulative cadmium exposure or liver cadmium. The difference in the transfer coefficient (KCO) between cadmium workers and referents increased linearly with increasing cumulative exposure without evidence for a threshold. The estimated mean decrement in KCO for a cadmium worker employed 5 or more years with a cumulative exposure of 2000 yr.microgram.m-3 (exposure to the current UK control limit of 50 micrograms.m-3 for a working lifetime of 40 yr) lies between 0.05 and 0.3 mmol.min-1.kPa-1.l-1 (95% confidence interval). This decrement is consistent with the functional and radiological changes of emphysema observed in this group of workers. PMID- 2895212 TI - Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy. AB - A phase I/II study of granulocyte colony stimulating factor (G-CSF) was undertaken in patients with advanced malignancy receiving melphalan to determine the granulocyte response, side-effects, and pharmacokinetics. Patients received doses of 1-60 micrograms/kg intravenously. There were 3 patients at each dose level. Before chemotherapy the immediate effect of G-CSF was a transient depression in circulating neutrophils followed by a dose-dependent rise. Neutrophil counts up to 80 X 10(9)/l were achieved. G-CSF administration following melphalan reduced the period of neutropenia caused by melphalan. G-CSF was well tolerated and the only clinical observation that appeared related to G CSF administration was slight bone pain during some infusions. G-CSF was rapidly cleared from the blood with a mean half-life of 110 min for the second phase. Reductions in the number of days of neutropenia following cytotoxic chemotherapy may reduce the morbidity and mortality of chemotherapy. PMID- 2895213 TI - Hodgkin's disease prognosis: a directly predictive equation. AB - 586 patients with Hodgkin's disease diagnosed between 1970 and 1979 were staged and treated in the same way. Multivariate analysis was used to delineate the prognostic roles of several clinical features at diagnosis. A multiple regression analysis was applied to an exponential model for survival-time distribution, which proved to fit the data accurately. Several clinical characteristics were studied and those that could singly discriminate survival significantly were chosen as predictive variables for the multiple regression. These were: sex, age, stage, histological subtype, presence of constitutional symptoms, mediastinal mass, and erythrocyte sedimentation rate (ESR), and haemoglobin and serum albumin concentrations. ESR, stage, histological subtype, and age proved to be the best prognostic factors, while sex and albumin had minor value. The presence of symptoms, mediastinal bulk, and haemoglobin were not so important. A linear equation for the six variables was derived to calculate the estimated median survival time for any given patient. This equation was validated on an external group of 179 similar patients. PMID- 2895214 TI - Prospective randomised trial of tamoxifen versus surgery in elderly patients with breast cancer. AB - 116 patients aged 70 or over who were judged to have surgically resectable cancer of the breast were prospectively randomised to tamoxifen 20 mg daily or surgical resection. At a median follow-up of three years, local relapse or progression was seen in 15 (25%) of 60 patients in the tamoxifen group and 21 (37.5%) of 56 in the surgical arm. Distant metastases occurred in 8 (13%) in the tamoxifen group and in 10 (18%) in the surgical arm. There were 13 deaths in the tamoxifen group and 11 in the surgical arm, of which 8 and 9, respectively, were attributable to breast cancer. Disease-free survival did not differ between the groups. PMID- 2895215 TI - Treatment of childhood acute lymphoblastic leukaemia. PMID- 2895216 TI - Ageing of elderly Britons: the direction of geriatric medicine. PMID- 2895217 TI - Cochlear implantation for the profoundly deaf. PMID- 2895219 TI - Prone or supine for preterm babies? PMID- 2895218 TI - Acanthamoeba keratitis. PMID- 2895220 TI - Chemotherapy for the primary treatment of osteosarcoma: population effectiveness over 20 years. AB - Examination of the survival rate of 5-year cohorts with primary osteosarcoma registered by the Thames Cancer Registry between 1963 and 1982 and followed up to the end of 1984 showed a borderline significant improvement in survival (test for trend p = 0.05) for patients aged under 25 years at registration, but not for patients 25-64 years. A Cox's proportional hazards model was used to identify effects of sex, period of treatment, whether the patient received chemotherapy, and experience of the hospital. For patients aged under 25 years, a significant (p = 0.02) trend of improved survival was seen among the most recent cohort, and the greater the treatment experience of the hospital, possibly the better the results (p = 0.11), although selective referral cannot be excluded as a reason for this finding. Chemotherapy was not independently associated with survival. Period of treatment, chemotherapy, and experience of hospital were not associated with improved survival for patients aged 25-64. Recent clinical trials for primary osteosarcoma have contributed to an apparent improved survival through selection of patients with good prognosis. Claims for the efficacy of new regimens should be assessed in clinical practice by population monitoring through the analysis of cancer registers. PMID- 2895221 TI - The expanded spectrum of toxocaral disease. AB - Among 137 members of 30 families, 6% (and 8% of those aged under 15 years) were seropositive for toxocara antibodies. In these seropositive subjects and in 84 patients known to have raised toxocara titres the commonest clinical features were abdominal pain, hepatomegaly, anorexia, nausea, vomiting, lethargy, sleep and behaviour disturbances, pneumonia, cough, wheeze, pharyngitis, cervical adenitis, headache, limb pains, and fever. 61% of patients with raised toxocara titres had recurrent abdominal pain. Eosinophilia was in many cases associated with a raised toxocara titre, but 27% of patients with high titres had normal eosinophil counts. Toxocariasis is common, especially in children, and is associated with clinical features that are generally regarded as non-specific but together form a recognisable symptom complex. Toxocariasis should be considered in the differential diagnosis of such symptoms and especially in recurrent abdominal pain, which might otherwise be labelled as idiopathic. The absence of eosinophilia does not exclude toxocariasis. PMID- 2895222 TI - Assessment of a device for trans-telephonic control of defibrillation. AB - The safety and efficacy of a device allowing the trans-telephonic control of defibrillation have been assessed in 32 attempted defibrillations performed in 29 patients. The initial rhythm was atrial fibrillation in 27; ventricular tachycardia in 4; and ventricular flutter in 1. Satisfactory voice and ECG transmission were established in all cases. The mean time taken by the patient unit to dial and activate the base station was 20.3 seconds. The mean defibrillator charge time was 5.5 seconds to 50 joules and 9.3 seconds to 360 joules. A total of 84 synchronised and 5 unsynchronised shocks were delivered satisfactorily. Lay persons were trained to use the patient unit, and were able to operate the device at home. This device has the potential for rapid defibrillation of patients who develop ventricular fibrillation outside hospital. PMID- 2895223 TI - Incompatibility between fat emulsion and calcium plus heparin in parenteral nutrition of premature babies. PMID- 2895224 TI - Lipid deposition in parenteral infusion lines. PMID- 2895225 TI - Growth during early teenage pregnancies. PMID- 2895226 TI - Neopterin in clinical medicine. PMID- 2895227 TI - Penicillin and meningococci. PMID- 2895228 TI - Agency nurses and violence in a psychiatric ward. PMID- 2895229 TI - Percutaneous removal of atheromatous plaques. PMID- 2895230 TI - Transdermal potential and bacterial colonisation of intravascular catheters. PMID- 2895231 TI - Amoxycillin/clavulanate resistant Escherichia coli. PMID- 2895232 TI - One-minute endoscopy room test for Campylobacter pylori. PMID- 2895233 TI - Crohn's disease in married couples. PMID- 2895234 TI - Antigliadin and antireticulin antibodies in coeliac disease. PMID- 2895235 TI - Gemfibrozil-induced headache. PMID- 2895236 TI - Oral rehydration without chloride. PMID- 2895238 TI - Anti-neutrophil cytoplasm antibodies 1988. PMID- 2895237 TI - Post-Chernobyl radiocaesium exposure in the UK. PMID- 2895239 TI - Mechanical ventilation for the newborn. PMID- 2895240 TI - Conference sponsorship. PMID- 2895241 TI - Consultant's night on the house. PMID- 2895242 TI - Gastroenterology. PMID- 2895244 TI - Trials that fail. PMID- 2895243 TI - Helmets for cyclists. PMID- 2895245 TI - Social work in children. PMID- 2895246 TI - Dialysis for diabetics. PMID- 2895247 TI - Screening for early ovarian cancer. PMID- 2895248 TI - Specific IgE antibodies to Bordetella pertussis after immunisation in infancy. PMID- 2895249 TI - Concomitant infection by human herpesvirus 6, HTLV-I, and HIV-2. PMID- 2895250 TI - Sex as a risk factor for HTLV-I spread among intravenous drug abusers. PMID- 2895251 TI - HIV monitoring of pregnant women. PMID- 2895252 TI - False-positive anti-HIV tests on blood donations. PMID- 2895253 TI - Case definitions for paediatric AIDS applied to African children seen in Belgium. PMID- 2895254 TI - Effects on naltrexone on infantile autism. PMID- 2895255 TI - Endothelial cell proliferation and diabetic retinopathy. PMID- 2895256 TI - Interference in modified immunoradiometric assay for thyrotropin. PMID- 2895257 TI - Surgery in advanced breast cancer. PMID- 2895258 TI - Medical negligence: a suitable case for treatment? PMID- 2895259 TI - The first seizure in adult life. Value of clinical features, electroencephalography, and computerised tomographic scanning in prediction of seizure recurrence. AB - 408 adults (age 16 and over) were followed up after their initial seizure. The actuarial risk of recurrence was highest in the early weeks. For those seen within the first week, the risk of recurrence was 52% by the end of 3 years. In univariate analysis, the only clinical variable that was associated with recurrence was the time of day at which the initial seizure occurred. There was a tendency, that did not reach statistical significance, for younger age (less than 50 years) and a family history of seizures of any type, including febrile convulsions, to be associated with recurrence. Such risk factors appear to be additive, so that the risk of recurrence at 1 year for a subject with all three factors is about three times that of a subject with none of them. Sex, type of seizure, and features of the electroencephalogram were not of predictive value. Computerised tomographic scanning revealed tumours in 3% of subjects, and these individuals were particularly likely to have recurrent seizures. PMID- 2895260 TI - Severity of anaemia and operative mortality and morbidity. AB - In a case-control study of 125 surgical patients who declined blood transfusions for religious reasons operative mortality was inversely related to the preoperative haemoglobin level, rising from 7.1% for patients with levels above 10 g/dl to 61.5% for those with levels below 6 g/dl. Mortality rates were also related to blood loss during surgery, rising from 8% for patients who lost less than 500 ml to 42.9% for those who lost more than 2000 ml. Both preoperative haemoglobin level and operative blood loss should be considered in assessing the need for preoperative transfusion. In our study no patient with a haemoglobin level above 8 g/dl and operative blood loss below 500 ml died. PMID- 2895261 TI - Use of X chromosome inactivation analysis to establish carrier status for X linked severe combined immunodeficiency. AB - Analysis of X chromosome inactivation in T-lymphocyte DNA from two obligate carriers of X-linked severe combined immunodeficiency showed a non-random pattern. This method was then used to establish carrier status in at-risk females in X-linked pedigrees. It was further used to differentiate between X-linked and autosomal recessive inheritance of the disease when the mode of inheritance was not clear from the pedigree. In addition, a mother of a boy affected by the sporadic form of the disease was found to have non-random X inactivation in her T lymphocytes and she is therefore a carrier of the X-linked disease. PMID- 2895262 TI - Hypertension and hyperinsulinaemia: a relation in diabetes but not essential hypertension. AB - To investigate the hypothesis that insulin resistance is concerned in the pathogenesis of essential hypertension fasting glucose/insulin and fasting insulin/C-peptide ratios were measured in non-obese normotensive and hypertensive diabetic and non-diabetic subjects. Patients with essential hypertension had normal fasting serum insulin values and normal fasting glucose/insulin ratios; by contrast, the hypertensive non-insulin-dependent diabetic subjects had higher fasting serum insulin and lower glucose/insulin ratios than either normotensive diabetic or non-diabetic patients. Both hypertensive and normotensive diabetic subjects had higher fasting C-peptide values than those without diabetes. Hypertensive diabetic patients had the highest insulin/C-peptide ratios, indicating low hepatic insulin extraction rates. These findings suggest that hyperinsulinaemia is not causally related to essential hypertension but that it may contribute to the hypertension of non-insulin-dependent diabetes in association with low hepatic insulin clearance. PMID- 2895263 TI - Xenogeneic antibodies and atopic disease. AB - Xenogeneic antibodies can survive food processing procedures with their biological activity intact and even enhanced. These antibodies can be absorbed from the human gut, and will function both as antigens and antibodies in the human immune system. Antibodies to bovine gamma globulins (BGG) have been detected in human sera and the family of anti-BGG antibodies must include anti idiotypic antibodies, very low doses of which can influence the immune response. The hypothesis is that the human immune system may be primed by low-level exposure to xenogeneic antibodies specific for those human allergens which are ubiquitous in the farm environment, such as pollens, mites, and moulds, the result being a deleterious and inappropriate response on subsequent exposure to these allergens. Dairy products are the most important source of xenogeneic antibodies in the western diet, and the hypothesis may partly explain the association between cow's milk and allergies to substances other than milk proteins. PMID- 2895264 TI - Post-colonoscopic retrograde ileography. PMID- 2895265 TI - Pneumonia in childhood. PMID- 2895266 TI - Intratracheal drugs. PMID- 2895267 TI - Cardiology via the oesophagus. PMID- 2895268 TI - Life under pylons. PMID- 2895269 TI - Transporting smoke. PMID- 2895270 TI - Is routine urinalysis worthwhile? PMID- 2895271 TI - Differences in hospital asthma management. AB - Asthma management was audited prospectively for one year in a large teaching hospital. Full details were available on 77% of all patients admitted, or readmitted, with asthma during that year (150 of 195 admissions). 64 patients were admitted to general wards with a special interest in respiratory medicine, and 86 to general wards without this specialist interest. Cases in the two groups were similar in terms of age, previous severity of asthma, previous treatment, and initial pulse rate. Fewer cases in the non-specialist group were treated with oral corticosteroids (67%, vs 83%), had regular peak flow recordings (42%, vs 73%), or were given return appointments (56%, vs 92%); and fewer had their regular inhaled therapy increased after discharge (28%, vs 55%). At interview 13 days later, more patients from the non-specialist group reported sleep disturbance (41%, vs 23%), morning chest tightness (55%, vs 37%), ow wheeze on 1 flight of stairs (58%, vs 34%). 20% of first admissions in the non-specialist group were readmitted within the year, compared to 2% of the group treated on wards with a specialist interest in respiratory medicine. These data suggest that the intensive management of asthmatic patients, practised in respiratory units, prevents much unnecessary morbidity. PMID- 2895273 TI - Clinical fontanometry in the newborn. PMID- 2895274 TI - Human papillomavirus and cervical cancer. PMID- 2895272 TI - Diagnosis and treatment of coronary disease: comparison of doctors' attitudes in the USA and the UK. AB - Two panels of doctors, one in the USA and one in the UK, were asked to indicate how appropriate they judged a series of possible indications for coronary angiography and coronary artery bypass graft (CABG) operations. "Appropriateness" was defined with respect to possible benefit to the patient and excluded considerations of cost. The indications were presented as a series of detailed clinical situations in which the procedure might be used, and for each indication individual panel members rated appropriateness on a scale of 1 to 9. The US panel judged more indications appropriate than did the UK panel, and there was more agreement among the members of the US panel than among those of the UK panel. Although the two panels tended to rate the appropriateness of the indications in the same order, the UK panel placed more emphasis than did the US panel on the importance of symptoms and the amount of medical treatment. Application of the panels' ratings to two groups of patients who had had coronary angiography showed that 17% and 27% of the investigations had been inappropriate by the standards of the US panel, whereas 42% and 60% were inappropriate by the UK panel ratings. 13% of the CABG operations studied were inappropriate by the US and 35% by the UK panel ratings. PMID- 2895275 TI - Treatment of myocarditis with OKT3 monoclonal antibody. PMID- 2895276 TI - Acute, ascending cord ischaemia after mobilisation of a stable quadriplegic patient. PMID- 2895277 TI - Dependence on a common cough syrup. PMID- 2895278 TI - Platelets and clubbing. PMID- 2895279 TI - Ultrasonography in the diagnosis of hereditary angioneurotic oedema. PMID- 2895280 TI - Classical versus lower segment caesarean section in very pre-term deliveries. PMID- 2895281 TI - Epidural anaesthesia and avoidance of postpartum stress urinary incontinence. PMID- 2895282 TI - Recombinant alpha 2-interferon treatment in children with chronic hepatitis B. PMID- 2895283 TI - Warfarin, spontaneous hyphaemas, and intraocular lenses. PMID- 2895284 TI - Thrombolysis after myocardial infarction. PMID- 2895285 TI - Prenatal diagnosis of alpha-1-antitrypsin deficiency using polymerase chain reaction. PMID- 2895286 TI - Assessing radiation risks. PMID- 2895287 TI - Hyperbaric oxygen in neonatal care. PMID- 2895288 TI - Residual carcinoma-in-situ of contralateral testis after chemotherapy. PMID- 2895289 TI - Interferon-alpha for idiopathic myelofibrosis. PMID- 2895290 TI - High-dose intravenous methylprednisolone for idiopathic myelofibrosis. PMID- 2895291 TI - How actively should dystocia be treated? PMID- 2895292 TI - Dithiocarbamates and Parkinson's disease. PMID- 2895293 TI - Fetal cell tropism of human parvovirus B19. PMID- 2895294 TI - Incident at Shaifa Hospital. PMID- 2895295 TI - Public health, a multidisciplinary function. PMID- 2895296 TI - Unused drugs for developing countries. PMID- 2895297 TI - Alternative to "aaah". PMID- 2895299 TI - Monkeypox virus in liver and spleen of child in Gabon. PMID- 2895298 TI - Childhood malignancies in West Hull. PMID- 2895300 TI - Systemic lupus erythematosus and ulcerative colitis. PMID- 2895301 TI - Treating gallstones. PMID- 2895302 TI - Immunosuppressive effect of pneumococcal vaccine contaminated with blood-group-A like substance. PMID- 2895303 TI - Antibiotics for Escherichia coli gastroenteritis. PMID- 2895304 TI - Haemorrhagic pancreatitis after ERCP in patients with alpha 1-antitrypsin deficiency. PMID- 2895305 TI - Synchronisation of a disturbed sleep-wake cycle in a blind man by melatonin treatment. PMID- 2895306 TI - Empty sella syndrome and pituitary apoplexy. PMID- 2895307 TI - Atypical virus particles in HIV-1-associated persistent generalised lymphadenopathy. PMID- 2895308 TI - Dementia due to undiagnosed meningioma. PMID- 2895309 TI - Gemfibrozil plus cholestyramine in familial hypercholesterolaemia. PMID- 2895310 TI - Conservative management of prostate cancer. PMID- 2895311 TI - Data sheets: a consumer perspective. PMID- 2895312 TI - AIDS in the United States: education and litigation. PMID- 2895313 TI - The euthanasia debate. PMID- 2895314 TI - The secret observation of children in hospital. PMID- 2895315 TI - Anonymous testing for HIV antibodies. PMID- 2895316 TI - Triple regimen of selective decontamination of the digestive tract, systemic cefotaxime, and microbiological surveillance for prevention of acquired infection in intensive care. AB - All 324 patients admitted over sixteen months to a general intensive therapy unit (ITU) were prospectively studied to assess the effect of a novel prophylactic antibiotic regimen on the incidence of acquired infection. Consecutive control (161 patients) and test (163 patients) groups were analyzed. In the control group, antibiotic administration was determined by clinical and microbiological evidence of infection. In the test group, treatment consisted of a triple regimen of selective decontamination of the digestive tract (polymyxin E, tobramycin, and amphotericin B) administered throughout the ITU stay, systemic cefotaxime administered for the initial four days, and regular microbiological screening of multiple sites. The test group showed a striking and consistent reduction in colonisation of the digestive tract with aerobic gram-negative bacilli, and there was a substantial reduction in the incidence of acquired infection (24% to 10%). Mortality in certain categories of patients was also reduced. There is now a considerable body of evidence to justify the more widespread use of this selective parenteral and enteral anti-sepsis regimen (SPEAR) in general intensive care practice. PMID- 2895317 TI - Antibody-dependent enhancement of human immunodeficiency virus type 1 infection. AB - Two components of human serum enhance human immunodeficiency virus type 1 (HIV-1) infection and mask HIV-1 neutralising antibody activity. The first is heat stable, unique to HIV-1 seropositive sera, and is removed by protein-A chromatography. The second is heat-labile and ubiquitous; it is found in normal serum and is removed by heating at 60 degrees C for 1 h or by treatment with cobra venom anticomplementary protein. Additionally, complement component C3 deficient serum lacks the labile activity although Clq deficient serum contains the labile factor. The data suggest that the two components are antibody and the alternative pathway of complement fixation. The mechanism of action does not involve an increase in either complement-mediated cytolysis or syncytium formation. The activity has been identified in 11 of 16 patients tested to date. PMID- 2895318 TI - Malignant transformation of solar keratoses to squamous cell carcinoma. AB - 1689 people aged 40 years and over were examined over a 5-year period to determine the incidence of malignant transformation of solar keratoses. They were seen on 2 consecutive years on 4267 occasions; a total of 21,905 solar keratoses were present on the first visit. A squamous cell carcinoma (SCC) developed within 12 months on 28 of the 4267 occasions. Where accurate mapping of both SCCs and pre-existing solar keratoses was available, it was found that 10/17 (60%) SCCs arose from a lesion diagnosed clinically as a solar keratosis in the previous year and the other 7 (40%) SCCs on what had been clinically normal skin 12 months previously. The risk of malignant transformation of a solar keratosis to SCC within 1 year was less than 1/1000. The cost-effectiveness of treating all solar keratoses to prevent the development of SCC is questionable. PMID- 2895319 TI - Influence of postoperative anticoagulant treatment on patient survival after femoropopliteal vein bypass surgery. AB - To examine whether anticoagulants given after autologous saphenous bypass surgery influenced patient survival 119 patients who received such a graft for obliterative arterial disease were recruited for a controlled clinical trial. Patients were randomly assigned to start, in the second postoperative week, phenprocoumon (60 patients) or no treatment (59 patients). The median duration of survival for all patients was greater than 60 months, and the 75%-quartile was 39.0 (SE of the median 3.9) months. 10 patients died in the treated group and 20 in the control group. The treated group had a greater probability of survival (p less than 0.023, Breslow; p less than 0.043, Mantel). Graft occlusions occurred in 11 patients in the treatment group and in 17 controls. When these patients were excluded from the analysis, the difference in probability of survival between the two groups remained significant (p less than 0.009, Breslow; p less than 0.013, Mantel). PMID- 2895320 TI - Partial trisomy chromosome 5 cosegregating with schizophrenia. AB - Schizophrenia was associated with a distinct autosomal abnormality in two related mildly dysmorphic individuals. The finding of cosegregation of schizophrenia and a partial trisomy of chromosome 5 in the family suggests a potential location of a gene or genes linked to schizophrenia. PMID- 2895321 TI - Microbial selective decontamination in intensive care patients. PMID- 2895322 TI - Buspirone--a radical advance in the treatment of anxiety? PMID- 2895324 TI - British surgery must change. PMID- 2895323 TI - HIV infection: obstetric and perinatal issues. PMID- 2895325 TI - Child health in the nordic countries. PMID- 2895326 TI - Revised definition of pre-eclampsia. AB - Different measures of raised blood pressure were analysed in 16,211 singleton pregnancies to determine the most effective way of identifying pre-eclampsia. Increments from baseline in the first half of pregnancy were considered as well as absolute levels. A combination of a high maximum diastolic pressure with a large increase from baseline was better for identifying a group with pre eclamptic features than either measurement on its own. A first diastolic pressure below 90 mm Hg, a subsequent increase of at least 25 mm Hg, and a maximum reading of at least 90 mm Hg gave appropriate criteria. These were applied to a second set of 15,624 singleton pregnancies and successfully identified a group with pre eclamptic features. Fewer women were identified as pre-eclamptic than with criteria modified from an existing definition widely used in Britain. The women excluded by the new criteria had the features of mild chronic hypertension rather than pre-eclampsia. The new definition is simple to use but like all other definitions of pre-eclampsia cannot be precise. PMID- 2895327 TI - Unilateral facial pain in patients with lung cancer: a referred pain via the vagus? AB - In 8 patients presenting with unilateral facial pain, subsequent investigation revealed an ipsilateral lung tumour. The interval between presentation with the pain and the discovery of the lung cancer varied between 6 wk and 4 yr. Radiotherapy cured the facial pain in 7 cases. Facial pain may be caused by lung cancer, and could be referred to the face via the vagus nerve. PMID- 2895328 TI - Transient traumatic cortical blindness in children. PMID- 2895329 TI - Pancreas transplantation for diabetes? PMID- 2895330 TI - Virus of enterically transmitted non-A, non-B hepatitis. PMID- 2895331 TI - 25 years of implanted intracardiac pacers. PMID- 2895332 TI - Triptorelin in treatment of cervical and vaginal dysplasia related to papillomavirus. PMID- 2895333 TI - Epidemic aluminium phosphide poisoning in northern India. PMID- 2895334 TI - Spontaneous resolution of multifocal gastric enterochromaffin-like cell carcinoid tumours. PMID- 2895335 TI - Caffeine cubes. PMID- 2895336 TI - Topoisomerases in human disease. PMID- 2895337 TI - Importance of cranial magnetic resonance imaging in diagnosis of multiple sclerosis without supraspinal signs. PMID- 2895338 TI - Thrombolytic therapy for acute myocardial infarction--round 2. PMID- 2895339 TI - Selective loss of HLA-A,B,C locus products in colorectal adenocarcinoma. PMID- 2895340 TI - Bismuth, Campylobacter, and ulcer relapse. PMID- 2895341 TI - Diltiazem for tardive dyskinesia and tardive dystonia. PMID- 2895342 TI - Transient cerebellar diaschisis. PMID- 2895344 TI - Molecular mechanisms in familial and sporadic cancers. PMID- 2895343 TI - Prenatal exclusion of hereditary retinoblastoma. PMID- 2895345 TI - Thalidomide for graft-versus-host disease. PMID- 2895346 TI - Analgesic activity of morphine-6-glucuronide. PMID- 2895347 TI - Meleney's synergistic gangrene. PMID- 2895348 TI - Neopterins as markers in bone marrow transplantation. PMID- 2895349 TI - Respiratory tract infections and importation of exotic birds. PMID- 2895350 TI - Will antibody-dependent enhancement of HIV-1 infection be a problem with AIDS vaccines? PMID- 2895351 TI - IgG antibodies to HIV-1 in urine of HIV-1 seropositive individuals. PMID- 2895352 TI - Follow-up of neuropathy from 2',3'-dideoxycytidine. PMID- 2895353 TI - Tuberculosis and the new CDC case definition for AIDS. PMID- 2895354 TI - Increase in childhood carcinomas in north-west England. PMID- 2895355 TI - Temazepam capsules; soft or hard? PMID- 2895356 TI - Audit on place of birth. PMID- 2895357 TI - Miscarriage and delayed depression. PMID- 2895358 TI - Myocardial depression after anaphylaxis. PMID- 2895359 TI - Cryopreserved zygote intrafallopian transfer for anonymous oocyte donation. PMID- 2895360 TI - Pertussis vaccine: court finds no justification for association with permanent brain damage. PMID- 2895361 TI - Dispensing forged prescriptions. PMID- 2895362 TI - Impact of sexual and physical abuse on women's mental health. AB - The level of psychiatric symptomatology was assessed with the General Health Questionnaire and the Present State Examination in a random community sample of women. Subsequently it was ascertained which of the women had been the victims of sexual or physical abuse, in either childhood or adult life. Women with a history of being abused were significantly more likely to have raised scores on both measures of psychopathology and to be identified as psychiatric cases. 20% of women who had been exposed to sexual abuse as a child were identified as having psychiatric disorders, predominantly depressive in type, compared with 6.3% of the non-abused population. Similar increases in psychopathology were found in women who had been physically or sexually assaulted in adult life. These findings indicate that the deleterious effects of abuse can continue to contribute to psychiatric morbidity for many years. PMID- 2895363 TI - Predicting insulin-dependent diabetes. AB - 719 first-degree relatives of diabetic children were followed up to assess the value of HLA haplotype sharing and of islet-cell antibodies (ICA) for prediction of insulin-dependent diabetes (IDDM). Within a maximum of 8 years' follow-up (3384 patient-years of observation) 16 unaffected relatives (5 parents and 11 siblings) became insulin dependent. The cumulative risk of becoming insulin dependent by age 25 was 16% for siblings sharing two HLA haplotypes with the proband, 9% for those sharing one haplotype, and zero for those sharing none. 13 of 24 (54%) subjects positive for complement-fixing ICA on three or more occasions became insulin dependent, as against 1 of 30 (3%) with noncomplement fixing ICA alone and 2 of 665 (0.3%) ICA-negative subjects; by life-table analysis the risks after 8 years of known ICA status are 76%, 3%, and 0.6%, respectively. In terms of total time at risk ICA-positive family members had a relative risk of 75.2 compared with ICA-negative individuals. With positivity for complement-fixing ICA the relative risk was 188.5. PMID- 2895364 TI - Doppler uteroplacental waveforms in pregnancy-induced hypertension: a re appraisal. AB - Uteroplacental waveforms in 32 untreated patients with pregnancy-induced hypertension (PIH) were compared with those in 32 carefully matched women with normal pregnancies (alpha = 0.05; beta = 0.80 for 30% difference between groups). Although some of the PIH patients showed high-resistance waveforms, both high and low resistance patterns were obtained from all controls and all but 1 PIH patient, and there was no overall difference in pulsatility index between groups (p greater than 0.1). Further careful prospective evaluation is necessary to determine the diagnostic value of doppler uteroplacental velocimetry in clinical practice. PMID- 2895365 TI - In-vitro production of HIV-specific antibody in children at risk of AIDS. AB - To improve on the early diagnosis of human immunodeficiency virus (HIV) infection, 37 children born to HIV-infected mothers and 22 controls were investigated for in-vitro synthesis of IgG antibody directed against HIV components. For 14 of 16 infected children western blot showed HIV-specific IgG in the supernatants of cultures of their peripheral blood lymphocyte cultures. HIV-specific IgG synthesis was detected in cultures from 4 out of 17 seropositive children aged under 15 months with no clinical or laboratory evidence of infection. No HIV-specific IgG production was observed in cultures from 4 uninfected children or 22 controls. The results show that the demonstration of in vitro production of HIV-specific IgG may help in the early diagnosis of HIV infection in children. PMID- 2895367 TI - Patch up the menopause. PMID- 2895366 TI - Role of epithelium in EBV persistence and pathogenesis of B-cell tumours. AB - EBV has long been thought to be primarily a B-lymphotropic virus. A manifestation of this tropism is the association of the virus with a variety of B-cell lymphoproliferative disorders and tumours. However, there is now considerable evidence to suggest that the permissive cell type for EBV replication is epithelial and that infection of B cells may be a secondary, and, from the point of view of the virus, an unimportant consequence. A re-evaluation of the role that epithelium plays in viral persistence and of the importance of the immune response in the development of persistent infection indicates that T-cell mediated immunity to the epithelial infection is critical in maintaining the normal delicate balance between virus and host. It also suggests that uncontrolled EBV replication in pharyngeal epithelium may be central to the evolution of some (or all) EBV-associated lymphomas. PMID- 2895368 TI - Medical research in the UK: their Lordships' view. PMID- 2895369 TI - Pulmonary aspergillosis. PMID- 2895370 TI - Campylobacter pylori and protein losing enteropathy in children. PMID- 2895371 TI - Central core disease. PMID- 2895372 TI - Management of diabetic renal involvement and disease. PMID- 2895373 TI - Polycystic ovaries--a common finding in normal women. AB - The prevalence of polycystic ovaries (PCO) in normal women of reproductive age was determined by pelvic ultrasound scanning of 257 volunteers who considered themselves to be normal and who had not sought treatment for menstrual disturbances, infertility, or hirsutism. All women had completed a menstrual history questionnaire. 99 women were on oral contraceptives at the time of the study. Of the 158 subjects who were not on oral contraceptives 18% had irregular cycles. 116 (73%) women had normal ovaries and 36 (23%) had PCO. 5 women had multifollicular ovaries and 1 had small, unstimulated ovaries. Only 1 woman with normal ovaries had an irregular menstrual cycle. Of the women with PCO, 76% had irregular cycles, and 6 of the 8 with regular cycles were hirsute. Women with and those without PCO differed in distribution of serum LH concentrations although the median values were similar. 25% of women with PCO had LH concentrations which exceeded the upper limit of the normal range. Thus PCO are common in normal women. Some of these women may have clinical and biochemical markers of PCO, which suggest that PCO in women who consider themselves to be normal is part of the same clinical spectrum as the classic Stein-Leventhal syndrome. PMID- 2895374 TI - Reliability of eliciting physical signs in examination of the chest. AB - Agreement between 24 physicians on the presence or absence of respiratory signs was investigated. The physicians were divided into six sets of 4; each set examined 4 patients with well-defined chest signs. There was generally poor agreement about particular signs. Overall, the 4 physicians in a set were in complete agreement only 55% of the time. Some signs such as wheezing seemed to be more reliably elicited than others such as whispering pectoriloquy. Comparison of diagnoses based on the clinical findings with the correct diagnoses supported by investigations showed that 28% of physicians' diagnoses were incorrect. The more often the examiners differed from the majority on the presence or absence of a sign, the more likely they were to make an incorrect diagnosis. A ranked order of the reliability with which chest signs are elicited would improve the teaching of chest medicine. PMID- 2895375 TI - Immunisation against hepatitis B. PMID- 2895376 TI - Xamoterol versus digoxin in heart failure. PMID- 2895377 TI - Aortic aneurysm presenting as deep venous thrombosis. PMID- 2895378 TI - Symptomless left-ventricular dysfunction and early drug treatment. PMID- 2895379 TI - Treatment of large basal-cell carcinomas with intralesional interferon-alpha-2a. PMID- 2895380 TI - Tyramine in wine and beer. PMID- 2895381 TI - Preliminary survival analysis of UK AIDS data. PMID- 2895382 TI - Isolation of HIV from mononuclear cells of patients receiving zidovudine. PMID- 2895383 TI - Adrenocortical lesions and AIDS. PMID- 2895384 TI - Detection of rabies antigen in canine parotid glands by dot-blot technique. PMID- 2895385 TI - Acellular pertussis vaccines and fatal infections. PMID- 2895386 TI - Possible exacerbation of myasthenia gravis by ciprofloxacin. PMID- 2895387 TI - Leucocyte-derived interferon-alpha in patients with antibodies to recombinant IFN alpha 2b. PMID- 2895388 TI - Motoneurone disease. PMID- 2895389 TI - Brazilian purpuric fever. PMID- 2895390 TI - Molecular basis of mitochondrial myopathies. PMID- 2895391 TI - Kearns-Sayre syndrome with muscle mitochondrial DNA deletion. PMID- 2895392 TI - IgG subclass deficiency and chronic fatigue syndrome. PMID- 2895393 TI - Roughness of skin in food allergy. PMID- 2895394 TI - Aluminium and dialysis arthropathy. PMID- 2895395 TI - Hepatotoxicity of tetrahydroaminoacridine. PMID- 2895396 TI - A new kind of child abuse. PMID- 2895397 TI - Passive smoking. PMID- 2895398 TI - Penalising smokers and drinkers. PMID- 2895399 TI - Bilingual consultation. PMID- 2895400 TI - Screening for ovarian cancer by CA-125 measurement. PMID- 2895401 TI - Oronasal obstruction, lung volumes, and arterial oxygenation. PMID- 2895402 TI - Rapid resolution of subclavian vein thrombosis by tissue plasminogen activator. PMID- 2895403 TI - Use of right atrial electrocardiography through fluid column of central venous catheters. PMID- 2895405 TI - Mouth-to-mask respiration. PMID- 2895404 TI - Coronary risk factors in children. PMID- 2895406 TI - Tamoxifen versus surgery in elderly patients with breast cancer. PMID- 2895407 TI - Long-term treatment of alcoholic liver disease with propylthiouracil. PMID- 2895409 TI - Differential effects of enflurane on Glu- and ACH-induced chloride currents in Aplysia neurons. AB - The primary site of anesthetic action remains controversial. In addition to non specific actions of hydrophobic substances on the membrane, specific effects of volatile anesthetics on neuronal activity have been reported. In the present study, effects of enflurane on the chloride currents (ICl) induced by L-glutamic acid (Glu) and acetylcholine (ACh) in isolated Aplysia neurons were examined, using the 'concentration clamp' technique. Enflurane increased the peak amplitude of the ICl induced by low concentrations of Glu but decreased those evoked by higher concentrations of the agonist. The anesthetic accelerated both activation and desensitization phases of the Glu-induced ICl. On the other hand, the ACh induced ICl in the same neuron was depressed in an uncompetitive manner in the presence of enflurane. The desensitization phase was not affected, although the activation phase became more rapid and the mean open time obtained by noise analysis was shortened. These results suggest the existence of specific steps in the process of activation and desensitization of channels, at which the volatile anesthetic exerts differential effects on the postsynaptic currents. PMID- 2895408 TI - Effects of pancreastatin on insulin, glucagon and somatostatin secretion by the perfused rat pancreas. AB - Pancreastatin is a novel peptide, isolated from porcine pancreatic extracts, which has been shown to inhibit glucose-induced insulin release "in vitro". To achieve further insight into the influence of pancreastatin on pancreatic hormone secretion, we have studied the effects of this peptide on unstimulated insulin, glucagon and somatostatin output, as well as on the responses of these hormones to glucose and to tolbutamide in the perfused rat pancreas. Pancreastatin strongly inhibited unstimulated insulin release as well as the insulin responses to glucose and to tolbutamide. It did not significantly affect glucagon or somatostatin output under any of the above-mentioned conditions. These findings suggest that pancreastatin inhibits B-cell secretory activity directly, and not through an A-cell or D-cell paracrine effect. PMID- 2895410 TI - Free fatty acid inhibition of the insulin induction of glucose-6-phosphate dehydrogenase in rat hepatocyte monolayers. AB - Rat hepatocytes in monolayer culture were utilized to determine if the decrease in glucose-6-phosphate dehydrogenase (G6PD) activity resulting from the ingestion of fat can be mimicked by the addition of fatty acids to a chemically, hormonally defined medium. G6PD activity in cultured hepatocytes was induced several-fold by insulin. Dexamethasone or T3 did not amplify the insulin induction of G6PD. Glucose alone increased G6PD activity in cultured hepatocytes from fasted donors by nearly 500%. Insulin in combination with glucose induced G6PD an additional two-fold. The increase in G6PD activity caused by glucose was greater in hepatocytes isolated from 72 hr-fasted rats as compared to fed donor rats. Such a response was reminiscent of the "overshoot" phenomenon in which G6PD activity is induced well above the normal level by fasting-refeeding rats a high glucose diet. Addition of linoleate to the medium resulted in a significant suppression of insulin's ability to induce G6PD, but linoleate had no effect on the induction of G6PD activity by glucose alone. A shift to the right in the insulin-response curve for the induction of G6PD also was detected for the induction of malic enzyme and acetyl-CoA carboxylase. Arachidonate (0.25 mM) was a significantly more effective inhibitor of the insulin action than linoleate was. Apparently rat hepatocytes in monolayer culture can be utilized as a model to investigate the molecular mechanism by which fatty acids inhibit the production of lipogenic enzymes. In part, this mechanism of fatty acid inhibition involves desensitization of hepatocytes to the lipogenic action of insulin. PMID- 2895411 TI - Evolutionary implication of heterogeneity of the nontranscribed spacer region of ribosomal DNA repeating units in various subspecies of Mus musculus. AB - Genetic variability of the nontranscribed spacer (NTS) region within ribosomal DNA repeating units in the various subspecies of Mus musculus was determined. Mice belonging to several laboratory mouse strains were examined by means of Southern blot hybridization with a mouse ribosomal DNA probe. This probe encompasses the 3' end of the 28S ribosomal RNA (rRNA) gene and the following spacer. Restriction enzyme digestions of the liver DNAs from various wild mice revealed that each of the subspecies has a unique pattern in the spacer encompassing a distance approximately 10 kb downstream from the ribosomal gene. These restriction patterns permit the classification of mouse subspecies and also provide insights into the origin of the laboratory mouse strains. PMID- 2895412 TI - Variation in the number of alpha-globin loci in sheep. AB - Southern blot analysis was used to compare sheep and goat restriction endonuclease maps of the DNA region containing the alpha-globin genes. The identical digestion patterns observed in both species with three endonucleases (BamHI, BstEII, and PstI) show that in sheep a single chromosome normally bears two nonallelic alpha-globin genes positioned at the same distance as in goat. Variant digestion patterns with enzymes that cleave outside (BamHI and HindIII) and within (EcoRI) the alpha-globin loci allowed us to infer that chromosomes with different numbers of alpha-globin loci are also present in sheep. In particular, in the 60 sheep considered, four individuals were heterozygous (alpha alpha/alpha alpha alpha) and one was homozygous (alpha alpha alpha/alpha alpha alpha) for chromosomes with three loci and one individual was heterozygous for a chromosome with four loci (alpha alpha/alpha alpha alpha alpha). This variation in the number of copies of alpha-globin loci can be explained by means of unequal crossovers. PMID- 2895413 TI - Ribosomal DNA (rDNA) spacer polymorphism in mole rats. AB - Genetic differentiation of ribosomal DNA (rDNA) nontranscribed-spacer (NTS) polymorphism was analyzed in 50 individuals from 13 populations among the four chromosomal species (2n = 52, 2n = 54, 2n = 58, and 2n = 60) of subterranean mole rats of the Spalax ehrenbergi complex in Israel. Southern blot analysis with a mouse rDNA probe and two restriction enzymes, EcoRI and BamHI, revealed various sizes of major restriction fragments. The assumption that this variation is due to length polymorphism of NTS DNA was supported by the construction of restriction-site maps. On the basis of the EcoRI and BamHi fragment lengths, we could characterize the major types of NTS rDNA repeating units in each individual. Each member of the central population in the four chromosomal groups of mole rats has a characteristic combination of the NTS types, suggesting that the karyotype groups were genetically diverged. Some near-hybrid-zone populations reflect similarities with the rDNA spectra of a neighbor chromosomal group. This might have resulted from gene flow across the hybrid zones. PMID- 2895414 TI - Mitochondrial DNA variation and genetic structure in populations of Drosophila melanogaster. AB - The understanding of the genetic structure of a species can be improved by considering together data from different types of genetic markers. In the past, a number of worldwide populations of Drosophila melanogaster have been extensively studied for several such markers, including allozymes, chromosomal inversions, and quantitative characters. Here we present results from a study of restriction fragment-length polymorphisms of mitochondrial DNA (mtDNA) in 92 isofemale lines from many of the same geographic populations of D. melanogaster. Eleven restriction enzymes were used, of which four revealed restriction-site polymorphism. A total of 24 different haplotypes were observed, of which 18 were unique to single populations. In many populations, the unique haplotypes have reached high frequency without being observed in neighboring populations. A Wagner parsimony tree reveals that mutationally close variants show geographical clumping, suggesting local differentiation of mtDNA in populations. The Old-World and the New-World populations are differentiated, with the predominant Old-World haplotype being virtually absent from the New World. These results contrast with those for the nuclear genes, in which many loci show parallel clines in different continents, and suggest a common origin of D. melanogaster populations in North America. PMID- 2895415 TI - Restriction-map variation in natural populations of Drosophila melanogaster: white-locus region. AB - Restriction-map variation among 38 chromosomes collected from natural populations from around the world was surveyed using probes for a 45-kb region containing and surrounding the white locus. Insertion and deletion variation was more common in the regions flanking the white transcriptional unit, and restriction-site polymorphism appears to be most common 5' of the white locus. The frequencies of individual large insertions (suspected transposable elements) were low, although 37% of the chromosomes had at least one insertion in the white-locus region. The estimated level of nucleotide heterozygosity over the whole region was 0.012. There was little linkage disequilibrium among the polymorphic sites. In contrast to earlier reports of the variation in other regions of the Drosophila melanogaster genome, there seemed to be less linkage disequilibrium and perhaps more nucleotide polymorphism. PMID- 2895416 TI - Restriction fragment length polymorphisms in diploid and allotetraploid Gossypium: assigning the late embryogenesis-abundant (Lea) alloalleles in G. hirsutum. AB - We have determined the copy number of 21 genes in an allotetraploid and several diploid species of cotton by gel and dot blot hybridization with cloned cDNAs. The legumin A, legumin B, and all 18 unique Lea (late embryogenesis-abundant) cDNA sequences isolated from the AD allotetraploid Gossypium hirsutum are present in one copy in A, D, E, and F diploid species and in two copies in G. hirsutum. Gel blot analysis of DNAs digested with EcoRI or BamHI usually detects different sized fragments in A and D diploids. Conservation of these restriction fragment length polymorphisms in G. hirsutum allows most of these fragments to be assigned to their respective subgenomes. Furthermore, both subgenomes in G. hirsutum can be distinguished from those in the interfertile allotetraploid G. barbadense. These results show that physical mapping of both sets of chromosomes in an allotetraploid should be possible by segregation analysis. PMID- 2895418 TI - [Voluntary, ritual and collective tooth mutilation in traditional societies and their prolongation in industrial societies]. PMID- 2895417 TI - An RFLP adjacent to the maize waxy gene has the structure of a transposable element. AB - Two maize inbred lines harbor non-mutant waxy (Wx) genes that display restriction fragment length polymorphism (RFLP) upstream from the start of Wx transcription. Sequencing of this region in the two strains revealed a DNA insertion with the structural features of a transposable element. The insertion is 316 bp in length, has 15 bp imperfect inverted repeats and is flanked by a 5 bp direct repeat generated upon insertion. Sequences homologous to this insertion are present in multiple copies in maize and its relatives teosinte and Tripsacum but not in the more distantly related dicot tobacco. Finally, this element is not homologous with any previously described maize DNA insertion. PMID- 2895419 TI - Neurochemical, but not behavioral, deviations in the offspring of rats following prenatal or paternal inhalation exposure to ethanol. AB - In addition to its widespread social use, ethanol is used extensively as an industrial solvent. Inhalation exposures to ethanol which produce narcosis in maternal rats are not teratogenic. The present study sought to extend the previous research by including offspring from paternal exposures, and testing for behavioral disorders in the offspring following maternal or paternal exposures. Groups of 18 male (approximately 450 g) and 15 female (200-300 g) Sprague-Dawley rats were exposed 7 hours/day for six weeks or throughout gestation to 16000, 10000, or 0 ppm ethanol by inhalation and then mated with untreated rats. Litters were culled to 4 males and 4 females, and were fostered within 16 hours after birth to untreated dams which had delivered their litters within 48 hours previously. Offspring from paternally or maternally exposed animals performed as well as controls on days 10-90 in tests of neuromotor coordination (ascent on a wire mesh screen, rotorod), activity levels (open field, modified-automated open field, and running wheel), and learning ability (avoidance conditioning and operant conditioning). In addition, brains of 10 21-day-old pups were analyzed for neurochemical differences from controls in concentrations of protein and the neurotransmitters acetylcholine, dopamine, norepinephrine, 5-hydroxytryptamine, substance P, Met-enkephalin, and beta-endorphin. Levels of acetylcholine, dopamine, substance P, and beta-endorphin were essentially unchanged in the offspring of rats exposed to ethanol. Complex, but significant changes in levels of norepinephrine occurred only in paternally exposed offspring. 5 Hydroxytryptamine levels were reduced in the cerebrum, and Met-enkephalin levels were increased in all brain regions of offspring from both maternally and paternally exposed rats. PMID- 2895422 TI - [Two cases of Takayasu arteritis. Studies by light microscopy, transmission electron microscopy and polarization electron microscopy]. PMID- 2895421 TI - No glycolipid anchors are added to Thy-1 glycoprotein in Thy-1-negative mutant thymoma cells of four different complementation classes. AB - Recent evidence shows that the mature Thy-1 surface glycoprotein lacks the C terminal amino acids 113 to 143 predicted from the cDNA sequence and is anchored in the plasma membrane by a complex, phosphatidylinositol-containing glycolipid attached to the alpha-carboxyl group of amino acid 112. Here we studied the biosynthesis of Thy-1 in two previously described and two newly isolated Thy-1 deficient mutant cell lines. Somatic cell hybridization indicated that their mutations affected some processing step rather than the Thy-1 structural gene. The Thy-1 made by mutants of classes C, F, and H bound detergent but, in contrast to wild-type Thy-1, their detergent-binding moieties could not be removed by phospholipase C. In addition, tryptophan, which only occurs in position 124, was incorporated into Thy-1 of these mutants but not of wild-type cells. Last, the Thy-1 of wild-type but not mutant cells could be radiolabeled with [3H]palmitic acid. Together, these findings strongly suggest that mutants of classes C, F, and H accumulate a biosynthetic intermediate of Thy-1 which retains at least part of the hydrophobic C-terminal peptide. The Thy-1 of these mutants remained endoglycosidase H sensitive, suggesting that it accumulated in the rough endoplasmic reticulum or the Cis-Golgi. A different Thy-1 intermediate was found in a class B mutant cell line: the Thy-1 of this mutant was 2 kilodaltons smaller than the Thy-1 of other cell lines, did not bind detergent, and was rapidly secreted via a normal secretory pathway. PMID- 2895423 TI - Nucleotide sequence determination of point mutations at the mouse HPRT locus using in vitro amplification of HPRT mRNA sequences. AB - Cloning of genomic and cDNA sequences of mammalian genes has made it possible to analyze at the molecular level mutations induced by radiation and chemical mutagens. The X-linked HPRT gene is very suitable for these investigations because in addition to the availability of cell culture systems, HPRT mutants can also be obtained directly from the lymphocytes of mouse and man. Recently a new technique has been introduced by Saiki and co-workers which allows the cloning and sequencing of small specific DNA segments from total genomic DNA after in vitro amplification of those segments up to 200,000-fold (Saiki et al., 1985). We have adapted this so-called polymerase chain reaction (PCR) procedure in such a way that the entire mouse HPRT-coding region could be amplified, cloned and sequenced. Instead of genomic DNA, we have used RNA as template in the PCR reactions. This allows us to detect point mutations in HPRT exon sequences in a very efficient way, since the DNA sequence of all 9 exons, which are scattered over 34 kb of DNA, can be obtained from only one amplification experiment. We studied the nature of 3 N-ethyl-N-nitrosourea (ENU)-induced HPRT mutants from cultured mouse lymphoma cells. One contains an A:T----G:C transition, the second an A:T----T:A transversion, whereas the third mutant is the result of abnormal splicing events, probably due to a mutation in the 3' splice site of the first intron. PMID- 2895424 TI - DNA strand breaks and mutations caused by penbutolol, a beta blocker. AB - Sixteen beta-adrenergic receptor blockers were screened for their mutagenic potential using Salmonella typhimurium strains TA98 and TA100. All except penbutolol were found to be nonmutagenic. Penbutolol was cytotoxic to human fibroblasts and Chinese hamster V79 cells. These effects could be due to its ability to induce DNA-strand breaks detected by hydroxyapatite chromatography, which remained unrepaired within 1 h of incubation. Under the same conditions strand-breaking activity of propranolol, timolol and indenolol could not be detected. Three potential impurities of penbutolol were ineffective in causing DNA-strand breakage and one metabolite of this drug was found to be nonmutagenic. PMID- 2895420 TI - Different cis-acting DNA elements control expression of the human apolipoprotein AI gene in different cell types. AB - In mammals, the gene coding for apolipoprotein AI (apoAI), a protein of the plasma lipid transport system, is expressed only in the liver and the intestine. A series of plasmids containing various lengths of sequences flanking the 5' end of the human apoAI gene were constructed and assayed for transient expression after introduction into cultured human hepatoma (HepG2), colon carcinoma (Caco 2), and epithelial (HeLa) cells. The results showed that while most of these constructs are expressed in HepG2 and Caco-2 cells, none of them is expressed in HeLa cells. In addition, the results indicated that a DNA segment located between nucleotides -256 and -41 upstream from the transcription start site of this gene is necessary and sufficient for maximal levels of expression in HepG2 but not in Caco-2 cells, while a DNA segment located between nucleotides -2052 and -192 is required for maximal levels of expression in Caco-2 cells. Moreover, it was shown that the -256 to -41 DNA segment functions as a hepatoma cell-specific transcriptional enhancer with both homologous and heterologous promoters. These results indicate that different cis- and possibly trans-acting factors are involved in the establishment and subsequent regulation of expression of the apoAI gene in the mammalian liver and intestine. PMID- 2895425 TI - Neuroleptic-withdrawal cachexia. PMID- 2895426 TI - Possible teratogenicity of sulfasalazine. PMID- 2895427 TI - Enhancement of contractile responses to partial alpha-adrenoceptor agonists during warming in rat aorta. AB - We examined the effects of warming on the contractile responses to full and partial alpha-adrenoceptor agonists in rat aorta. The contractions elicited by norepinephrine and methoxamine were not affected during warming (40 degrees C, 42 degrees C), whereas those induced by clonidine and St 587 were significantly enhanced. KCl-induced contractions of rat aorta were not affected by warming. The dissociation constants of clonidine and St 587 at 40 degrees C were not different from those at 37 degrees C. At 40 degrees C, the receptor occupancy-contractile response curve of clonidine was a hyperbolic curve similar to that of methoxamine at 37 degrees C, although at 37 degrees C the curve was almost linear. The responses of St 587 at both 37 degrees C and 40 degrees C were related inversely hyperbolic to the receptor occupancy, but the receptor occupancy-contractile response curve was shifted to the left and upward during warming. Clonidine and St 587 elicited equal responses at lower fractional occupancies at 40 degrees C than at 37 degrees C. The relative efficacies of clonidine and St 587 to methoxamine were significantly augmented during warming. It is suggested that the contractile responses to partial alpha-adrenoceptor agonists in rat aorta are enhanced during warming, and that this effect is related to the intrinsic efficacy of the agonists rather than to any function of their relative selectivity for alpha 1- or alpha 2-adrenoceptors. Such enhancement is due to augmentation of the efficacy rather than to augmentation of the affinity of the agonists. PMID- 2895428 TI - [Gilles de la Tourette syndrome]. PMID- 2895429 TI - Influence of antipsychotics and serotonin antagonists on presynaptic receptors modulating the release of serotonin in synaptosomes of the nucleus accumbens of rats. AB - In the nucleus accumbens of rats the release of [3H]serotonin (5-HT) from superfused synaptosomes stimulated by 30 mM K+ was investigated. In the presence of 40 microM of the uptake inhibitor cocaine the release of [3H]5-HT was inhibited by 5-HT in a concentration-dependent manner (IC50 = 0.45 microM). The maximum inhibitory effect of 5-HT was 54% of controls. The inhibition of K+ stimulated release of [3H]5-HT induced by 5-HT was antagonized completely by methiothepine and clozapine, respectively, whereas methysergide had only a weak antagonizing effect in a concentration of 20 microM or less, haloperidol was ineffective. Furthermore, the synaptosomal K+-stimulated release of [3H]5-HT was also inhibited by dopamine (DA) in a concentration-dependent manner (IC50 = 0.1 microM). This inhibitory effect was antagonized by antipsychotic drugs, the rank order of antagonistic potencies was sulpiride greater than haloperidol greater than clozapine; methiothepine was ineffective. The experimental system (the K+ stimulated synaptosomal release of [3H]5-HT seems to be a suitable model for differentiating dopaminergic and/or serotonergic components of antipsychotics or other drugs on presynaptic receptors. PMID- 2895431 TI - Analgesia and the blood-brain barrier transport system for Tyr-MIF-1/enkephalins: evidence for a dissociation. AB - The blood-brain barrier is capable of transporting peptides with anti-opiate (Tyr MIF-1) and opiate (enkephalins) activity out of the central nervous system. The relationship of this transport system to the various actions of opiates remains unexplored. This study examined the relationship between the rate of transport and opiate-induced analgesia. Both restraint, a stress that provokes an opiate mediated analgesia, and the administration of morphine (12 mg/kg, i.p.) each induced an inhibition in the rate of transport. Such inhibition exhibited specificity, since the saturable, brain to blood transport of iodide remained unaltered. However, it was possible to dissociate analgesia and inhibition of transport. The onset and peak of analgesia, as measured by tail-flick latency induced by morphine, preceded the onset and peak of the inhibition of transport. Naltrexone, which blocks opiate-mediated analgesia, also induced inhibition of transport without any significant effect on tail-flick latency. (-) Naloxone but not (+) naloxone also weakly inhibited transport. Deprivation of food and water, associated with analgesia possibly mediated by the opiate, beta-endorphin, which is not transported out of the brain by this system, did not alter transport. These results suggest that while inhibition of transport and analgesia may occur together, these events probably represent two separate aspects of the action of opiates, that may even be mediated by separate receptor sites or peptides in the opiate family. PMID- 2895430 TI - The hypothermic response of mice to delta-9-tetrahydrocannabinol is enhanced by chlorpromazine, thioxanthenes, alpha-adrenoceptor antagonists and pentolinium but not by SCH 23390 or sulpiride. AB - Chlorpromazine, given either subcutaneously (0.375 mg/kg) or unilaterally into the preoptic/anterior hypothalamic area through a chronically implanted cannula (20 micrograms), was found to enhance the hypothermic response to delta-9 tetrahydrocannabinol (THC; 5 mg/kg i.p.) in unrestrained adult male MF1 mice, kept at 22 degrees C. In mg/kg terms, chlorpromazine was no more potent when injected into the preoptic/anterior hypothalamic area than when given subcutaneously. Phentolamine (54 micrograms) had no significant effect on hypothermia induced by THC when injected into the hypothalamus although it did enhance this response when given subcutaneously (15 mg/kg). Hypothermia induced by THC was also enhanced by flupentixol (0.375 mg/kg s.c.), piflutixol (23.4 micrograms/kg s.c.), pentolinium (5 mg/kg s.c.), prazosin (0.1875 mg/kg s.c.) and indoramin (6 mg/kg s.c.) but not by SCH 23390 (6 mg/kg s.c.) or sulpiride (40 mg/kg s.c.). When taken together with the results from a previous study, these data support the hypothesis that chlorpromazine enhances hypothermia induced in mice by THC by antagonizing alpha-adrenoceptors so as to decrease the capacity of the animals to minimise peripheral blood flow by vasoconstriction. The present data also support the hypothesis that flupentixol and piflutixol interacted with THC not by antagonizing dopamine at D1 or D2 receptors but rather by blocking alpha-adrenoceptors. PMID- 2895433 TI - Investigation of the effect of fluperlapine on the EEG in schizophrenic patients. AB - The investigations of the EEG during an open study with the antipsychotic drug fluperlapine in acute schizophrenic patients are reported. Due to ethical and practical considerations some of the common pharmaco-electroencephalographic procedures as well as placebo controlled study designs could not be applied in these patients. To overcome at least partly these limitations, intraindividual as well as interindividual correlations were used. They were computed between plasma concentrations of unchanged fluperlapine as well as its metabolite N-oxide fluperlapine, on one hand, and EEG variables, on the other. The intraindividual correlations can be computed either on the first day of the active treatment over various time points of that day (acute effects) or across several appointed treatment days always taking values at the same time during these days (chronic effects). The intraindividual correlations of a set of subjects were submitted to a sign test to obtain an overall result for the relation between the EEG and blood plasma levels of the drug. In this way an acute and a chronic effect of fluperlapine on the EEG could be shown consisting mainly of an increase in slow waves, a decrease in the alpha-activity and a tendency of beta-activity to decrease. A comparison of the correlations between the plasma levels of fluperlapine and the EEG variables with the correlations between the plasma levels of N-oxide fluperlapine and the EEG gives rise to the hypothesis that unchanged fluperlapine has a stronger effect on the EEG than its metabolite. PMID- 2895432 TI - Analgesic effects of intrathecally-applied alpha 2-adrenoceptor agonists in conscious, unrestrained sheep. AB - Intrathecal injections of small volumes of the alpha 2-adrenoceptor agonists, xylazine and clonidine, into the cervical region of the spinal cord of conscious unrestrained sheep produced a dose-dependent analgesia of the forelimbs as measured using a mechanical pressure device. Intravenous injection of the alpha 2 adrenoceptor antagonist, idazoxan completely abolished the analgesic effects of the intrathecally applied alpha 2-adrenoceptor agonists. Subsequent studies using [3H] clonidine injected at a similar dose and volume via the intrathecal catheters, indicated that the volume of drug used, 100 microliter, gave a localisation of the drug limited to about five vertebral segments around the catheter tip. PMID- 2895434 TI - Classification of psychotropic drugs by rat EEG analysis: the anxiolytic profile in comparison to the antidepressant and neuroleptic profile. AB - Electroencephalograms were recorded from the parietal and frontal cortex of freely moving rats held in constant vigilance by placing them in a slowly turning drum. The effects of 5 clinically effective anxiolytics, buspirone, meprobamate, phenobarbital, chlordiazepoxide and diazepam, were studied after intraperitoneal injection of different doses. After on-line fast Fourier transformation of the EEG signal, the drug effects were quantified by an Analysis of Variance. This resulted in a t profile for each drug dosage. Averaging the t profiles of all dosages of a drug results in a 'drug profile'. Averaging the drug profiles of the 5 anxiolytic drugs tested results in an 'anxiolytic profile'. This profile is characterized by a power decrease from 8 to 11 Hz and above 70 Hz and a power increase from 20 to 60 Hz. The anxiolytic profile is compared with the formerly defined antidepressant and neuroleptic profiles and can be clearly distinguished from the latter two. PMID- 2895435 TI - Adjunctive benzodiazepines in acute schizophrenia. AB - An open clinical trial was conducted on an unlocked ward investigating the use of benzodiazepines as adjunctive therapy with neuroleptics in managing acute exacerbation of chronic schizophrenia. Seventeen patients meeting DSM-III criteria for this disorder were treated. Patient response was monitored with use of the Brief Psychiatric Rating Scale and Beigel Mania Rating Scale. Our results indicate that those patients who received greater than 2 mg lorazepam equivalents daily had greater improvement at 4 days of treatment in comparison to those who received less than 2 mg lorazepam equivalents daily. PMID- 2895436 TI - [Prevalence and pathogenesis of folate deficiency in patients with quiescent or clinically mildly active Crohn disease]. PMID- 2895438 TI - Displaceable somatostatin binding sites in the gray matter and pyramidal paths of the human developing spinal cord. AB - The binding of the somatostatin analogue, 125I-iodo-Tyr-[Tyr0,D-Trp8]S14, to the foetal (18- and 24-week-old) and infant (newborn and 17-month-old) spinal cord was examined using in vitro autoradiography. Somatostatin binding sites were detected at cervical, thoracic and lumbosacral levels in foetal as well as in infant spinal cord. The radiolabelling was localized over the grey especially in the superficial layers of the dorsal horn including the substantia gelatinosa and the marginal zone. In foetal and newborn spinal cord, the direct and crossed pyramidal paths exhibited a substantial binding of the ligand. A similar labelling was not observed in the pyramidal paths of a 17-month-old child or in anencephalic newborn spinal cord or previously described in adult. These results emphasize the early presence of somatostatin binding sites during the ontogeny of the human spinal cord. Further, the transient appearance of somatostatin binding sites in the pyramidal paths, prior the myelination, raises the question whether somatostatin receptors could be involved in the maturation of certain normal paths. PMID- 2895437 TI - [Somatostatin in the treatment of acute pancreatitis. Our experience]. PMID- 2895439 TI - Properties of glycine-activated conductances in rat brain neurones. AB - The inhibitory responses to glycine, taurine, beta-alanine, 2-amino-5 phosphonovaleric acid (APV) were investigated in freshly isolated neurones from medulla oblongata and hippocampus of rat using concentration clamp, voltage clamp and intracellular perfusion techniques. All substances, when applied in a steplike manner, induced a rapid increase in the chloride permeability of the cellular membrane which slowly desensitized. The responses to all substances were blocked by external strychnine. Cross-desensitization experiments demonstrated that all substances tested activate the same system of membrane receptors. PMID- 2895441 TI - Changes in the activity of gamma-glutamyl transpeptidase in brain microvessels, astroglial cells and synaptosomes derived from rats with hepatic encephalopathy. AB - Prolonged thioacetamide treatment increased gamma-glutamyl transpeptidase (GGT) activity in the rat liver and induced neurological symptoms of hepatic encephalopathy (HE). The enzyme activity measured without an amino acid or peptide acceptor was increased in cortical capillaries and synaptosomes, but remained unchanged in astroglia isolated from the brains of hyperammonemic rats. In the presence of L-glutamine the activity of GGT was stimulated by about 60% in astroglial cells while in the capillaries and synaptosomes the amino acid stimulation was less pronounced. Glycylglycine also stimulated the GGT activity in the astroglia more (4-fold) than in cortical capillaries or synaptosomes (3 fold). Similar stimulatory effects of these gamma-glutamyl moiety acceptors on the GGT activity were observed in capillaries, glial cells and synaptosomes derived from the brains of rats with HE. These results indicate that GGT may be involved in the excessive accumulation of large neutral amino acids (and some peptides) in the brain of rats with HE. PMID- 2895440 TI - Differential activity of the endogenous antiopiate Tyr-MIF-1 after various intensities of stress. AB - Three forms of stress-induced analgesia (electric shock, forced water-swim and novelty) were used to examine the nature of the endogenous antiopiate system. It was hypothesized that a role of the antiopiate system may be to regulate the extent of antinociception within varying environments. The antiopiate properties of Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), which were manifest by reduction of opiate analgesia in mice on a hot-plate, were best expressed within a defined range of intensities. In each of the 3 analgesic situations, pre-administration of Tyr-MIF 1 (0.1 mg/kg) resulted in an antinociceptive effect after low to moderate stress but not after more intense stress. These observations indicate that the antiopiate system can function differentially under various environmental conditions, thus ensuring that the organism's responses to its perception of the immediate environment are appropriate and specific. PMID- 2895442 TI - Management of traumatic dental injuries in children. PMID- 2895443 TI - The passive protection of lambs against Clostridium perfringens type D with semi purified hyperimmune serum. AB - Weaned lambs, having a detectable level of maternal antibodies (1-2 units/ml) against C. perfringens type D, showed protective antitoxin levels lasting for 29 days after receiving a single parenteral dose of 200 units/kg hyperimmune serum. Lambs, having no maternal antibodies (less than 0,07 units/ml) to C. perfringens type D but receiving the same dose of hyperimmune serum, maintained protective antibody levels for only 21 days. Three weeks after the titres fell below the minimum protective level of 0,15 units/ml, both these groups were treated again in the same manner. The passive immunity conferred in both groups now lasted for 42 days. When the hyperimmune serum was administered to lambs already immunized by vaccination, a slight increase was noted in the antibody titre. PMID- 2895444 TI - [Treatment of hypertension and coronary disease]. PMID- 2895446 TI - Amplification of human int-2 in breast cancers and squamous carcinomas. AB - Murine int-2 is one of the genetic loci implicated in the induction of mouse breast cancers by murine mammary tumor virus. An homologous gene has recently been identified in the human genome (Casey et al., 1986). The human int-2 locus was found to be amplified 7- to 25-fold in 4 of 46 infiltrating ductal breast cancers and 30- to 60-fold in 2 of 8 squamous carcinomas of the head and neck region, but not in other cancers. All of the involved tumors had metastasized to regional lymphatics at the time of analysis and five exhibited clinically aggressive behavior. PMID- 2895445 TI - Genetic analysis and developmental regulation of testis-specific RNA expression of Mos, Abl, actin and Hox-1.4. AB - The pattern of Mos proto-oncogene RNA expression in the gonads of the sterile mouse mutants, dominant spotting (W), sex reversal (Sxr), testicular feminization (Tfm), hypogonadal (hpg), quaking (qk), two t-haplotypes, three X-autosomal translocations, and the YPOS strain, is consistent with its presence in haploid spermatids in the testes and in oocytes in the ovaries. In the male-sterile mouse mutants the pattern of expression of the testis-specific transcripts for Abl, actin, and the mouse homeobox Hox-1.4 genes is identical to that observed for Mos. However, during the postnatal onset of normal spermatogenesis we detected differences in the time of the appearance of the four transcripts. We detected Hox-1.4 transcripts at day 20, Mos at day 25, and Abl and actin at day 30, demonstrating a specific regulation of expression of each of these genes during haploid spermatid maturation in the mouse. Furthermore, comparison of Mos, Abl and actin RNA expression in mouse and rat testes revealed species-specific variations in the regulation of gene expression. PMID- 2895447 TI - [Multiple otogenic subdural abscesses]. PMID- 2895448 TI - Computer-aided three-dimensional reconstruction and measurement of the vestibular end-organs. AB - It is very valuable for temporal bone morphologists to be able to recognize temporal bone serial sections in three dimensions and to be able to measure temporal bone structures three-dimensionally. We can now do 3-dimensional reconstruction to visualize the structures of vestibular endorgans (utricular and saccular maculae) and measure these endorgans in space by means of a small computer system and software that we developed. As well as obtaining the dimensions--such as length and area--of the utricular and saccular maculae, we also found that (1) most of the utricular macula lies in one plane, which is the same as the plane of the lateral semicircular canal, (2) the saccular macula is shaped like part of a sphere, and (3) the angle between the two maculae is less than a right angle. Such knowledge is indispensable to the evaluation of the function of the utricular and saccular maculae. PMID- 2895449 TI - [Effect of the pharmacological modulation of the brain dopamine systems on epileptic activity in rats]. PMID- 2895451 TI - [Neurochemical mechanisms of the functioning of central links in the emetic reflex]. PMID- 2895450 TI - [Use of a polymetric method for studying neural transmission block in the autonomic ganglia (experimental and clinical research)]. PMID- 2895452 TI - Effect of beta-adrenergic receptor blockade on responses to acute hypoxemia in lambs. AB - We studied the effects of beta-adrenergic receptor blockade on general circulatory and metabolic responses to moderate (FIO2 = 0.09) acute hypoxemia in newborn (protocol 1) and 3-wk-old (protocol 2) lambs, and on regional blood flow distribution in newborn lambs (protocol 1). Via a left thoracotomy we placed an electromagnetic flow transducer around the ascending aorta and inserted various vascular catheters. After 2 days of recovery, the lambs were studied. In protocol 1, we measured cardiovascular variables and regional blood flow distribution during control conditions, after 45 min of acute hypoxemia, and after 0.5 mg/kg of propranolol during acute hypoxemia. In protocol 2, we measured cardiovascular variables during control conditions and after 45 min of acute hypoxemia with and without propranolol pretreatment. In both groups, propranolol limited the increase in cardiac output and heart rate caused by hypoxemia, and thus decreased oxygen delivery. However, propranolol also decreased oxygen consumption so that pulmonary arterial pO2 was either higher (protocol 1) or the same (protocol 2) as during acute hypoxemia alone. Neither metabolic acidosis nor hypothermia ensued. In protocol 1, propranolol decreased renal, carcass, and most importantly, myocardial blood flows. However, myocardial O2 consumption also fell, coronary sinus pO2 increased, and blood was redistributed toward the subendocardium, suggesting that myocardial perfusion improved. Thus, beta-adrenergic receptor blockade during acute moderate hypoxemia may have a beneficial effect by reducing total body and myocardial oxygen demand in excess of the reduction in oxygen delivery. PMID- 2895453 TI - [Surgical problems posed by abnormalities of testicular migration]. AB - Based on their experience and on a review of the literature, the authors study the surgical aspects of the undescended testis. A precise definition excluding the retractile testis is essential. Although the understanding of the pathogenesis remained incomplete, the present data give support to an early orchidopexy performed by a specialized surgeon following the failure of a human chorionic gonadotropin test. PMID- 2895455 TI - Clinically important adverse effects and drug interactions with H2-receptor antagonists: an update. AB - The H2-receptor antagonists cimetidine, ranitidine, and famotidine are well tolerated, with a low frequency and similar spectrum of adverse effects. The occasional problematic effects that have been associated with these agents include central nervous system symptoms (mental confusion, headache, and depression), rare cases of thrombocytopenia, and cardiovascular events related to the rate of intravenous infusion. Severe renal and hepatic impairment appear to be associated with a higher occurrence of central nervous system effects. Because the H2-receptor antagonists elevate gastric pH, bind to and inhibit the hepatic cytochrome P-450 enzyme system, and undergo renal tubular secretion, competition with other drugs sharing these pathways has resulted in a number of drug interactions, most of which are not clinically significant. The interaction that occurs with theophylline and warfarin when the cytochrome P-450 enzyme system is inhibited by cimetidine and ranitidine requires monitoring. Recent data suggest that administering cimetidine 800 mg at bedtime has less effect on the serum concentrations of warfarin and theophylline than other dosing regimens. Evidence to date indicates that famotidine does not bind to cytochrome P-450 to a significant extent, and interactions with drugs metabolized by this system have not been reported; however, clinical experience with this agent is very limited. PMID- 2895454 TI - Thermal characterization and transmitter analysis of single units in the preoptic and anterior hypothalamus of conscious ducks. AB - With a multibarrel assembly combining one carbon fiber micropipette as recording electrode and 6 pipettes for microiontophoretic application of drugs, the activity of neurons in the preoptic and anterior hypothalamic (POAH) region was extracellularly recorded in situ in conscious ducks implanted chronically with a device permitting hypothalamic thermal stimulation. Among 355 neurons 17% were identified as warm-responsive (warm units) and 20% as cold-responsive (cold units). In 58 warm and 56 cold units control discharge rates at 40 degrees C local temperature (F40) and temperature coefficients (delta F/delta T) were determined and presented as means +/- SEM. The F40 values of warm units (35.2 +/- 2.3 Imp . s-1) were significantly higher than of cold units (16.3 +/- 1.8 Imp . s 1). The delta F/delta T values (+1.77 +/- 0.15 and -1.77 +/- 0.19 Imp . s-1 . degree C-1) of warm and cold units were not different in absolute terms. In pilot experiments either activation or inhibition by lowering whole-body temperature was observed in both warm and cold units. Microiontophoretic application of one or more of the amines acetylcholine (ACh), 5-hydroxytryptamine (5-HT), and noradrenaline (NA) to warm and cold units revealed differences in their responsiveness to ACh, which more consistently stimulated cold units. NA inhibited the majority of warm units; 5-HT stimulated the majority of cold units. In both warm and cold units NA and ACh differed in their actions, with the latter amine more consistently producing activation. PMID- 2895456 TI - Histamine H2-receptor antagonists and high-density lipoproteins. AB - Epidemiologic evidence has shown that elevated levels of high-density lipoproteins (HDL) protect against the development of coronary heart disease (CHD). These observations have prompted the evaluation of various factors thought to affect HDL and its subspecies, HDL2 and HDL3. Numerous behavioral and physiologic factors have been shown to elevate HDL levels. These are currently being researched as potential tools in preventing CHD. Several pharmacologic agents are known to alter HDL levels. Studies show that patients with peptic ulcer disease treated with the H2-receptor antagonist cimetidine show significant elevations in their HDL, HDL2, and HDL3 profiles. In contrast, ranitidine has no effect, or may even decrease HDL levels. These divergent effects may be related to differences in pharmacologic activity unrelated to H2-receptor blockade. It should be noted that many of the variables affecting HDL levels were not controlled in these studies, and definite conclusions should not be extrapolated to the general population at risk for CHD. Currently, well-controlled trials to study the effect of cimetidine on HDL levels are in progress. PMID- 2895457 TI - Treatment of solar urticaria with terfenadine. AB - Treatment with the H1 receptor antagonist terfenadine increased significantly the dose of radiation required for weal and flare formation in 5 patients with idiopathic solar urticaria. The dose of radiation required to produce immediate erythema localised to the irradiation site was unchanged by terfenadine. The weal and flare reaction in solar urticaria, but not the immediate erythema, is mediated by histamine acting on the H1 receptor. PMID- 2895458 TI - [Various theories on the pharmacological treatment of stable exercise-induced angina pectoris]. PMID- 2895459 TI - Avoiding the pitfalls in primary care orthopedics. PMID- 2895461 TI - [Periodic respiration during sleep at high altitude. Effects of a hypnotic benzodiazepine, loprazolam]. AB - Sleep and respiration studies were carried out in 12 subjects (9 males, 3 females) at an altitude of 4,800 metres, during effect of a French expedition in the Himalayas. The effect of loprazolam, a hypnotic benzodiazepine, was investigated in a double-blind, 2 parallel group, 1 mg loprazolam versus placebo trial. Sleep was evaluated by means of electroencephalographic recordings and questionnaires. The effects of altitude in each subject were intercurrent wakefulness increase, slow wave sleep and paradoxical sleep decrease and nocturnal periodic breathing. The mean duration of sleep apnea episodes was 12 seconds with a maximum of 24 seconds. These episodes occurred during stages 1 or 2 of sleep and during paradoxical sleep. Female subjects exhibited less periodic breathing than males. Acclimatization to high altitude increased total sleep time, stage 3 duration and percentage of paradoxical sleep. Loprazolam tended to decrease stage 2 latency and did not worsen slow wave sleep depression or episodes of apnea. Normal amounts of slow wave sleep and intrasleep wakefulness appeared in the loprazolam group after acclimatization. PMID- 2895462 TI - [Postoperative hypoglycemia after excision of pheochromocytoma. A case]. AB - A case of hypoglycaemia consecutive to excision of a bilateral phaeochromocytoma in a 33-year old patient with Sipple's syndrome is reported. The severity of the hypoglycaemia (1.3 mmol/l) accounted for the brain lesions which ultimately resulted in the patient's death. Eight cases of hypoglycaemia occurring in similar circumstances have been published. The condition is due to the massive release of insulin during the hours that follow removal of the tumour. This results in the persistence of the peri-operative hyperglycaemic stimulation and in the suppression of the previous inhibition of insulin secretion due to alpha adrenergic stimulation of catecholamines in the beta-cells of Langerhans' islets. PMID- 2895460 TI - [Metabolic and cardiovascular effects of beta-blockers taken by the mother in newborn infants]. AB - The effects of beta-blockers administered to mothers with arterial hypertension were investigated in 38 neonates of varying gestational age and weight. During the first 48 hours of extra-uterine life, heart rate was continuously monitored and blood pressure and glycaemia were measured every 3 hours. Left ventricular function was studied by echocardiography on the first day post-partum, once again between the 5th and 10th days. Hypoglycaemia was observed in 42% of the neonates; 47% had one or several episodes of bradycardia and 2 had arterial hypotension. Most important, a significant improvement of left ventricular function was observed between the first and the 5th-10th days. This time-related change was not found in a control group. The cardiac dysfunction was more pronounced in neonates who had an episode of bradycardia, and although it is usually asymptomatic, it probably accounts for the fortunately rare cardiovascular collapses observed in some newborn babies. PMID- 2895463 TI - [Manifestation of diabetic gastroparesis during treatment with somatostatin]. PMID- 2895464 TI - [Temporal arteritis: a syndrome. From Horton's disease to periarteritis nodosa]. AB - Four cases of histologically proven temporal arteritis presenting with atypical clinical, anatomical or evolutive features and raising nosological problems concerning the type of vasculitis involved are presented. In patients with temporal arteritis, some elements are suggestive of periarteritis nodosa. They include peripheral neurological lesions, renal or pleuro-pulmonary lesions and the histological appearance of the temporal artery. Diagnosing periarteritis nodosa in a case of temporal arteritis leads to a special therapeutic strategy. PMID- 2895465 TI - [Value of the cyclophosphamide bolus in severe systemic diseases. Preliminary results]. AB - Twenty patients with severe systemic disease were treated intermittently with bolus intravenous injections of cyclophosphamide in doses of 0.5 to 1 g. The diseases were systemic lupus erythematosus in 9 cases, systemic necrotizing angiitis in 5 cases, Behcet's disease in 4 cases, Horton's disease in 1 case and dermatomyositis in 1 case. The rationale for this treatment was resistance to previous therapies in 9 patients, initial severity of the disease in 8 and the need for prompt reduction of corticosteroid dosage owing to side-effects in 3 other patients. No death or haemorrhagic cystitis was observed over a cumulative 120 month-patients period. Bacterial infection occurred in 6 cases, including pneumonia (3), and 1 case each of staphylococcal septicaemia, purulent meningitis and urinary infection: none of these infections were life-threatening, and all were cured without sequelae. The drug was well tolerated biologically, except for a moderate fall in neutrophils, lymphocytes and platelets. The systemic disease was stabilized or improved in 16 patients. It remained active and required corticosteroids at the same dosage level in 4 cases. It is concluded that bolus injections of cyclophosphamide are well tolerated in short-term treatments but that their effectiveness must be confirmed by controlled studies. PMID- 2895466 TI - [Muscarinic poisoning induced by bethanechol in renal insufficiency]. PMID- 2895467 TI - The present status of tardive dyskinesia and akathisia in the treatment of schizophrenia. AB - Motor disturbance is a major disadvantage of the antipsychotic drugs currently available for the treatment of schizophrenia. Acute akathisia is a dose-related side-effect comprising a subjective awareness of inner tension and characteristic patterns of restless movement. The natural history of akathisia is unclear, and several variants of the condition are seen in older patients on maintenance antipsychotic medication. These include acute akathisia that has persisted, and tardive akathisia which tends to be associated with signs of tardive dyskinesia. Tardive akathisia and tardive dyskinesia share some pharmacological characteristics which raises the possibility that common elements of pathophysiology underlie the 2 conditions. Tardive dyskinesia, comprising oro facial dyskinesia and choreiform trunk and limb movements, has come to symbolize the complications of long-term antipsychotic drug treatment, although the condition is often little more than a mild social handicap and is manifest in only a minority of patients receiving such treatment. This paper discusses the treatment and patient variables that may be considered as risk factors for tardive dyskinesia. Some of the inconsistencies in the relevant literature may be explained by a speculative sub-classification of tardive dyskinesia into early and late forms. The interaction of advancing age, drug treatment and the schizophrenic disease process in the development of late dyskinesia is discussed. PMID- 2895468 TI - Serologic differentiation of virus strains of hemorrhagic fever with renal syndrome (HFRS) by monoclonal antibodies. PMID- 2895469 TI - Identification of the second chromophore of Escherichia coli and yeast DNA photolyases as 5,10-methenyltetrahydrofolate. AB - Denaturation of DNA photolyase (deoxyribodipyrimidine photolyase, EC 4.1.99.3) from Escherichia coli with guanidine hydrochloride or acidification to pH 2 released, in addition to FAD, a chromophore with the spectral and chromatographic properties of a reduced pterin. Treatment of the enzyme with iodine prior to acidification converted the chromophore to a stable, oxidized derivative, which was resolved by HPLC into four species with identical spectral properties. The same species, in the same distribution, were obtained from the yeast enzyme. The material isolated from the iodine-oxidized enzyme was shown to be a pterin by conversion to pterin-6-carboxylic acid with alkaline permanganate and was found to release glutamate upon acid hydrolysis. The presence of 10-formylfolate in the isolated, oxidized chromophore was demonstrated by absorption and fluorescence spectroscopy and by deformylation and conversion to folic acid. Analysis of the distribution of polyglutamates revealed that the four species identified by HPLC corresponded to the tri-, tetra-, penta-, and hexaglutamate derivatives of 10 formylfolate. The results were consistent with gamma linkages in the triglutamate derivative with additional glutamates linked via the alpha-carboxyl group of the preceding residue. Treatment with rat plasma hydrolase produced the monoglutamate derivative of 10-formylfolate. The native, enzyme-bound form of the folate cofactor was identified as 5,10-methenyltetrahydrofolylpolyglutamate by effecting release and isolation at low pH to protect the 5,10-methenyl bridge and preserve the reduced pyrazine ring structure. PMID- 2895470 TI - Assembly of functional proton-translocating ATPase complex in yeast mitochondria with cytoplasmically synthesized subunit 8, a polypeptide normally encoded within the organelle. AB - A mitochondrial gene from Saccharomyces cerevisiae encoding a hydrophobic membrane protein, subunit 8 of the F0/F1-type mitochondrial ATPase complex, has been functionally replaced by an artificial nuclear gene specifying an imported version of this protein. The experiments reported here utilized a multicopy expression vector (pLF1) that replicates in the nucleus of yeast cells and that carries an inserted DNA segment, specifying a precursor protein (N9/Y8) consisting of subunit 8 fused to an N-terminal cleavable transit peptide (the leader sequence from Neurospora crassa ATPase subunit 9). The successful incorporation of the imported subunit 8 into functional ATPase complexes after transformation with pLF1 expressing N9/Y8 was indicated by the efficient genetic complementation of respiratory growth defects of aap1 mit- mutants, which lack endogenous subunit 8. The reconstitution of ATPase function was confirmed by biochemical assays of ATPase performance in mitochondria and by immunochemical analyses that demonstrated the assembly of the cytoplasmically synthesized subunit 8 into the ATPase complex. Reconstitution of ATPase function required the cytoplasmically synthesized subunit to have a transit peptide. The strategy for importation and reconstitution developed for subunit 8 leads to a systematic approach to the directed manipulation of mitochondrially encoded membrane associated proteins that has general implications for exploring membrane biogenesis mechanistically and evolutionarily. PMID- 2895472 TI - cDNA cloning of the immunoglobulin heavy chain binding protein. AB - A cDNA library was constructed from size-fractionated poly(A)+ RNA prepared from a murine pre-B-cell hybridoma expressing high levels of immunoglobulin heavy chain binding protein (BiP) and mu heavy chains. Transformed bacterial colonies were screened for recombinant plasmids containing cDNA coding for BiP by hybrid selected mRNA translation. A clone, pMBiP, containing a 736-base-pair insert was shown to encode the protein. Translation in vitro of hybridoma mRNA selected by hybridization to the pMBiP cDNA yielded a single polypeptide of BiP-like size. The authenticity of this mRNA was verified by comparing the peptides obtained by the limited proteolysis of its in vitro translation product with those obtained from the in vivo produced BiP. Likewise, the authenticity of the cDNA insert was verified by an RNase A protection assay of heteroduplex molecules obtained by annealing a uniformly labeled single-strand copy of the cDNA clone with the same mRNA selected by hybridization and tested by translation. The nucleotide sequence of this clone enabled us to deduce the carboxyl-terminal 142 amino acids of BiP and to establish its kinship with the 70-kDa heat shock protein family. The finding of a single copy of the BiP gene in DNA blots of mouse and rat implies that the BiP-related RNA transcripts constitutively expressed in various murine tissues and cell lines are indeed products of the same gene. These findings imply that BiP plays a more general role than previously anticipated on the basis of the discovery of its association with immunoglobulin heavy chains. PMID- 2895471 TI - Human retinoblastoma susceptibility gene: genomic organization and analysis of heterozygous intragenic deletion mutants. AB - A gene in chromosome region 13q14 has been identified as the human retinoblastoma susceptibility (RB) gene on the basis of altered gene expression found in virtually all retinoblastomas. In order to further characterize the RB gene and its structural alterations, we examined genomic clones of the RB gene isolated from both a normal human genomic library and a library made from DNA of the retinoblastoma cell line Y79. First, a restriction and exon map of the RB gene was constructed by aligning overlapping genomic clones, yielding three contiguous regions ("contigs") of 150 kilobases total length separated by two gaps. At least 20 exons were identified in genomic clones, and these were provisionally numbered. Second, two overlapping genomic clones that demonstrated a DNA deletion of exons 2 through 6 from one RB allele were isolated from the Y79 library. To confirm and extend this result, a unique sequence probe from intron 1 was used to detect similar and possibly identical heterozygous deletions in genomic DNA from three retinoblastoma cell lines, thereby explaining the origins of their shortened RB mRNA transcripts. The same probe detected genomic rearrangements in fibroblasts from two hereditary retinoblastoma patients, indicating that intron 1 includes a frequent site for mutations conferring predisposition to retinoblastoma. Third, this probe also detected a polymorphic site for BamHI with allele frequencies near 0.5/0.5. Identification of commonly mutated regions will contribute significantly to genetic diagnosis in retinoblastoma patients and families. PMID- 2895473 TI - Cloning and expression of a cDNA for the T-cell-activating protein TAP. AB - The T-cell-activating protein TAP is a murine phosphatidylinositol-anchored glycoprotein whose expression is controlled by the Ly-6 locus. Previous studies have suggested an important role for this protein in physiological T-cell activation. Using oligonucleotide probes, we have now isolated a cDNA clone whose predicted sequence would encode a protein with an NH2-terminal sequence identical to that of the TAP molecule. Further analysis of the predicted protein sequence revealed a cysteine-rich protein with a hydrophobic domain at the COOH terminus and without N-linked glycosylation sites--all features consistent with our previous analysis of the TAP protein. In Southern blot analysis, the Ly-6.2 cDNA clone detects a multigene family and a restriction fragment length polymorphism that maps precisely to the Ly-6 locus. Expression of the cDNA clone in COS cells demonstrates that it codes for TAP and clarifies the relationship between the epitopes recognized by various alpha Ly-6 monoclonal antibodies. Finally, we have studied the expression of Ly-6 mRNA in a variety of cell lineages. Ly-6 transcripts were detected in all organs examined, including spleen, kidney, lung, brain, and heart. This demonstrates that the Ly-6 locus is transcriptionally active in a wide range of organs and suggests that the role of TAP or TAP-like proteins might extend to other tissues. PMID- 2895475 TI - Close correlation between restriction fragment length polymorphism of the L-MYC gene and metastasis of human lung cancer to the lymph nodes and other organs. AB - Restriction length fragment polymorphism of the L-MYC gene was examined in DNAs from lung cancer tissues and normal tissues of 51 Japanese patients with lung cancer. In individual patients, no difference was seen between the restriction length fragments of the two alleles of L-MYC [6-kilobase (kb) and 10-kb fragments in EcoRI digests] in lung cancer tissues and normal tissues. But a striking correlation was found between the restriction length fragment polymorphism pattern of L-MYC and the extent of metastasis, particularly to the lymph nodes at the time of surgery: Patients with only the L band (10 kb) had few lymph node metastatic lesions, whereas patients with either the S band (6 kb) or the S and L bands almost always had lymph node metastatic lesion. A similar correlation was found between the presence of the S band and metastases to other organs. This correlation was particularly marked in cases of adenocarcinoma. These results indicate a clear genetic influence on metastases and a consequent poor prognosis for certain patients of lung cancer; L-MYC restriction length fragment polymorphism is thus shown to be a useful marker for predicting the metastatic potential of human lung cancer. PMID- 2895476 TI - Alzheimer's disease: coated vesicles, coated pits and the amyloid-related cell. AB - The amyloid-related cell (ARC) of the neuritic plaques of Alzheimer's disease revealed numerous cytoplasmic projections surrounding extracellular amyloid material. It is proposed that ARC-coated vesicles fuse with the cell membrane, forming coated pits, which may empty their secretory material into the extracellular space where polymerization of amyloid filaments could occur. PMID- 2895474 TI - Isolation and sequencing of a cDNA coding for the human DF3 breast carcinoma associated antigen. AB - The murine monoclonal antibody (mAb) DF3 reacts with a high molecular weight glycoprotein detectable in human breast carcinomas. DF3 antigen expression correlates with human breast tumor differentiation, and the detection of a cross reactive species in human milk has suggested that this antigen might be useful as a marker of differentiated mammary epithelium. To further characterize DF3 antigen expression, we have isolated a cDNA clone from a lambda gt11 library by screening with mAb DF3. The results demonstrate that this 309-base-pair cDNA, designated pDF9.3, codes for the DF3 epitope. Southern blot analyses of EcoRI digested DNAs from six human tumor cell lines with 32P-labeled pDF9.3 have revealed a restriction fragment length polymorphism. Variations in size of the alleles detected by pDF9.3 were also identified in Pst I, but not in HindIII, DNA digests. Furthermore, hybridization of 32P-labeled pDF9.3 with total cellular RNA from each of these cell lines demonstrated either one or two transcripts that varied from 4.1 to 7.1 kilobases in size. The presence of differently sized transcripts detected by pDF9.3 was also found to correspond with the polymorphic expression of DF3 glycoproteins. Nucleotide sequence analysis of pDF9.3 has revealed a highly conserved (G + C)-rich 60-base-pair tandem repeat. These findings suggest that the variation in size of alleles coding for the polymorphic DF3 glycoprotein may represent different numbers of repeats. PMID- 2895477 TI - Kinetics of activation of the potassium conductance in the squid giant axon. AB - A quantitative re-investigation of the time course of the initial rise of the potassium current in voltage-clamped squid giant axons is described. The n4 law of the Hodgkin-Huxley equations was found to be well obeyed only for the smallest test pulses, and for larger ones a good fit of the inflected rise required use of the expression (1-exp[-t/tau n1])X-1(1-exp[-t/tau n2]), where both of the time constants and the power X varied with the size of the test pulse. Application of a negative prepulse produced a delay in the rise resulting mainly from an increase of X from a value of about 3 at -70 mV to 8 at -250 mV, while tau n1 remained constant and tau n2 was nearly doubled. The process responsible for generating this delay was switched on with a time constant of 8 ms at 4 degrees C, which fell to about 1 ms at 15 degrees C. Analysis of the inward tail currents at the end of a voltage-clamp pulse showed that there was a substantial external accumulation of potassium owing to the restriction of its diffusion out of the Schwann cell space, which, when duly allowed for, roughly doubled the calculated value of the potassium conductance. Computations suggested that the principal effect of such a build-up of [K]o would be to reduce the fitted values of tau n1 and tau n2 to two-thirds or even half their true sizes, while the power X would generally be little changed; but it would not affect the necessity to introduce a second time constant, nor would it invalidate our findings on the effect of negative prepulses. PMID- 2895478 TI - On the mechanism of a high-frequency force generator in outer hair cells isolated from the guinea pig cochlea. AB - Isolated mammalian outer hair cells elongate or shorten respectively by several micrometres when electrically hyperpolarized or depolarized. The experiments in this paper were designed to locate the force-generating mechanism that drives length changes in outer hair cells, and to determine some of its basic properties. The whole-cell mode of the patch-clamp technique was used to stimulate cells electrically and to perfuse them with specific drugs. The pattern of displacement of cellular organelles, and the relative displacements of the cell base and apex during electrical stimulation with the cell mechanically anchored at various points along its length, suggest that the force-generating mechanism is distributed throughout the length of the cell. Further experiments altering the shape, volume and intracellular pressure of outer hair cells suggest that the mechanism is closely associated with the plasma membrane. These experiments also demonstrate that the characteristic tubular shape of outer hair cells is maintained by membrane-associated structures with elastic properties that enable the cell to return to its original shape after deformation. The mechanism controlling length changes may, therefore, be composed of two elements in parallel, namely a force generating element and a passive elastic element. Inhibitors of ATP synthesis, or the presence of the non-hydrolysable ATP analogue AMP.PNP, perfused into outer hair cells, failed to inhibit length changes. Drugs against actin, including phalloidin, cytochalasin B and cytochalasin D, and against tubulin, including colchicine, nocodazole and colcemid, also failed to inhibit length changes. We conclude that the force-generating mechanism is, therefore, unlike most other forms of cell motility, and possible alternative hypotheses are briefly discussed. PMID- 2895479 TI - Generalization of the discriminative stimulus properties of 8-hydroxy-2-(di-n propylamino)tetralin (8-OH-DPAT) and ipsapirone to yohimbine. AB - Rats were trained with either 8-OH-DPAT (0.2 mg/kg) or ipsapirone (10 mg/kg) versus saline in a 2-lever discrimination task. Tests of generalization were then conducted with yohimbine. All drugs were administered IP 15 min before testing. In 8-OH-DPAT-trained subjects, 85% of the responses following yohimbine (3 mg/kg) were on the drug-appropriate lever. Likewise, yohimbine (6 mg/kg) yielded 86% drug-appropriate responses in ipsapirone-trained rats. Previous studies have provided evidence that both 8-OH-DPAT and ipsapirone have high affinity for 5 HT1A receptors and the anxiolytic-like activity of the latter drug has been attributed to its activity at those receptors. In contrast, yohimbine is an alpha 2 adrenergic antagonist, has negligible affinity for the 5-HT1A receptor, and is generally regarded as being anxiogenic. The present data, which indicate a high degree of similarity between the stimuli induced by yohimbine, 8-OH-DPAT, and ipsapirone, suggest that a re-evaluation of the presumed mechanisms of actions of these drugs is in order. PMID- 2895480 TI - Stimulus generalization of 1-(3-trifluoromethylphenyl)piperazine (TFMPP) to propranolol, pindolol, and mesulergine. AB - Using standard operant procedures with rats trained to discriminate the serotonin (5-HT) agonist 1-(3-trifluoromethylphenyl)piperazine (TFMPP) (0.5 mg/kg) from saline, tests of stimulus generalization and stimulus antagonism were conducted with propranolol, pindolol, and mesulergine. Neither propranolol nor mesulergine antagonized the TFMPP stimulus (pindolol was not evaluated as an antagonist). However, TFMPP-stimulus generalization occurred with all three agents. These results suggest that the TFMPP-stimulus may involve both a 5-HT1B and a 5-HT1C mechanism and further suggest that propranolol, pindolol, and mesulergine may be capable of acting as agonists at certain populations of serotonin receptors. PMID- 2895481 TI - Perinatal exposure to cannabinoids alters neurochemical development in rat brain. AB - Adult female rats received daily oral doses of delta 9-tetrahydrocannabinol (delta 9-THC), delta 8-THC and cannabidiol (CBD) throughout gestation and lactation. The offspring were sacrificed at various ages and tissue samples of cerebral cortex and striatum were assayed for alpha 1-adrenergic and D2 dopaminergic receptors, respectively. In addition, tyrosine hydroxylase activity was determined in the striatum. The Kd for ligand binding to alpha 1 receptors in the cerebral cortex was significantly increased in 10-day-old offspring exposed to CBD. Significant increases in the Bmax of these receptors occurred at 20 days of age following perinatal exposure to delta 9-THC or delta 8-THC. Exposure to CBD increased the Kd of D2 receptors in the striatum of 10 and 20-day-old offspring compared to control. There were no significant treatment effects on the Bmax of D2 receptors in the striatum at any age. Tyrosine hydroxylase activity was significantly decreased only at 60 days of age in offspring exposed to delta 8-THC or CBD. These results differ from those previously reported with a crude marihuana extract, suggesting that changes in the development of brain catecholamine mechanisms resulting from perinatal exposure to marihuana extracts may be due to an additional constituent of the extract, interactions between specific cannabinoids or other unknown factors. PMID- 2895482 TI - Plant based antiamoebic drugs; Part I. Antiamoebic activity of phenanthroindolizidine alkaloids; common structural determinants of activity with emetine. PMID- 2895483 TI - Remoxipride, a selective dopamine D2 receptor antagonist, in tardive dyskinesia. AB - Remoxipride in a dose range of 150-600 mg/day was evaluated in a single-blind placebo controlled study in eight patients with persistent tardive dyskinesia (TD). Dyskinesia score was significantly reduced without an increase in parkinsonism. The maximum mean reduction in dyskinesia rating score was 44%. After withdrawal of remoxipride TD scores returned to baseline levels without rebound deterioration. A negative correlation between remoxipride concentrations and the dyskinesia scores were found. Adverse effects were few and mild and no clinically relevant changes were seen in clinical chemistry, haematology or cardiovascular assessments. It is concluded that remoxipride in the dose range used has anti-dyskinetic effects but does not induce parkinsonism. PMID- 2895484 TI - Observational analysis of the effects of kappa opioid agonists an open field behaviour in the rat. AB - An observational analysis of the effects of four kappa-opioid agonists on forward locomotion, rearing and grooming displayed by rats in a novel open field was undertaken. The doses of agonists used corresponded to those previously found to produce changes in food consumption. Ethylketocyclazocine (0.1 and 1 mg/kg), bremazocine (0.01 and 0.1 mg/kg) and tifluadom (0.3 and 3 mg/kg) exerted suppressant effects on all the activities monitored. Grooming behaviour appeared to be particularly sensitive to this action, being virtually abolished by the larger doses of these compounds. In contrast, the selective kappa agonist U 50,488H (0.1-3 mg/kg) only attenuated grooming at the two highest doses tested (1 and 3 mg/kg). None of the agonists tested produced stimulation of open field activity during the 1-h study. Reductions in activity occurred at doses previously found to increase and decrease food intake. It was therefore concluded that the hyperphagia induced by kappa agonists was not part of a more general behavioural activation, whilst reductions in food consumption probably result from a non-specific behavioural depression. PMID- 2895486 TI - Effect of injectable or inhalational anesthetics and of neuroleptic, neuroleptanalgesic, and sedative agents on tumor blood flow. AB - Among other parameters, varying blood flow values may be responsible for tumor-to tumor variabilities in the radiobiologically hypoxic cell fraction of experimental rodent tumors. To test whether changes in tumor blood flow may be caused by anesthetic agents often used in radiobiology, the effect of injectable and inhalational anesthetics and of neuroleptic, neuroleptanalgesic, and sedative agents on blood flow in subcutaneous DS-carcinosarcomas implanted in Sprague Dawley rats has been investigated using the 85Kr clearance technique. In conscious rats, 20-100 min after animal instrumentation mean blood flow is 0.62 +/- 0.17 ml/g/min (mean +/- SD) in 0.75 +/- 0.15 g tumors at a mean arterial blood pressure of 125 +/- 12 mm Hg. In animals receiving thiobutabarbital, chloral hydrate, or methoxyflurane tumor blood flow is somewhat higher than that measured in conscious rats. Tumor blood flow in animals receiving etomidate, ketamine-xylazine, fentanyl-fluanisone, or urethane is significantly lower than that in the thiobutabarbital group and somewhat lower than in the conscious animals. Blood flow values observed with midazolam, ketamine-midazolam, fentanyl droperidol, droperidol, diazepam, and pentobarbital are similar to those measured in conscious rats. Virtually no flow alterations with time are detectable in conscious rats and with most of the drugs used. In animals anesthetized with urethane or methoxyflurane, tumor blood flow increases and tumor vascular resistance diminishes slightly with time. PMID- 2895485 TI - Production of climbing behaviour in mice requires both D1 and D2 receptor activation. AB - The ability of SKF38393 (a D1 agonist), quinpirole (a D2 agonist), and apomorphine (a mixed D1/D2 agonist) to induce stereotyped climbing behaviour in mice was investigated. Apomorphine produced a dose-related increase in stereotyped cage climbing which lasted for up to 60 min. SKF38393 and quinpirole failed to produce climbing when administered alone. When given in combination intense apomorphine-like cage climbing was observed which lasted for up to 2 h. Apomorphine or the combination of SKF38393 and quinpirole also produced biting of the cage. The climbing behaviour produced by either apomorphine or SKF38393/quinpirole combinations was antagonised by either the D1 antagonist, SCH23390 or the D2 antagonist clebopride. These results demonstrate that both D1 and D2 receptor activation is necessary to produce apomorphine-like cage climbing in mice. PMID- 2895487 TI - Influence of gamma-radiation and cycloheximide on by hydrocortisone induced tyrosine aminotransferase and tryptophan-2,3-dioxygenase activity in the rat liver. PMID- 2895488 TI - [Beta adrenergic agonists. Mechanisms of action: lipid mobilization and anabolism]. AB - In this review, the results obtained in commercial livestock with certain beta adrenergic agonists (clenbuterol and cimaterol) having an anabolic potential associated with lipid mobilizing properties are considered. The first chapter summarizes major data concerning the effects of beta-agonists on growth and carcass composition in cattle, sheep and pigs. The effect of clenbuterol and cimaterol on carcass quality is to increase the deposition of protein while reducing fat accretion. Then, we briefly consider the physiology and pharmacology of the sympathoadrenal system with a special attention to the distribution and properties of beta-adrenoceptors of various tissues which are putative targets for the beta-adrenergic agonists. Several mechanisms liable to be responsible for the anabolic action of these compounds are also discussed. This chapter includes the evaluation of the effects of beta-agonist on central nervous system and pancreas. A special attention is devoted to their metabolic impact on adipose tissue and muscle. In isolated fat cells, beta-agonists promote stimulation of lipolysis associated with reduction of lipogenesis and of insulin action. The in vitro effects on adipocytes are consistent with the in vivo effects of the compounds. Beta-agonist impact on protein synthesis and muscle accretion is also discussed with reference: 1) to the vascular effects of the compounds that should modify the nutrient flow into the muscle, 2) to a reduction of proteolysis mainly observed for the moment in in vitro studies, 3) to the possible beta-adrenergic dependent enhancement of insulin action on the muscle. However, more direct experimental evidence is still needed to clearly assess the nature of the action(s) of such anabolic agents on muscle. PMID- 2895489 TI - Bioavailability of indenolol by nasal and intravenous routes. AB - The blood levels of indenolol were determined in rats following nasal and intravenous administration of 5 mg/kg body weight of the drug. The results indicate that the peak drug levels reach within 10 minutes of nasal administration. The areas under the curve for nasal and intravenous routes were found to be 65.67 (ng x hr)/ml and 65.32 (ng x hr)/ml respectively. The results suggest that nasal route may be of practical value for the administration of indenolol. PMID- 2895490 TI - Computer model of the absorption and distribution of colostral immunoglobulins in the newborn calf. AB - The transfer of immunoglobulin (Ig) isotypes (IgG1, IgG2, IgM), gamma-glutamyl transpeptidase (gamma-GT) and added D-xylose from colostrum to serum was investigated in newborn Holstein bull calves. Significant differences were observed in the time courses of the serum concentrations of these colostrum constituents following absorption from pooled colostrum. A computer model was devised to simulate the process of absorption of Ig isotypes, gamma-GT and D xylose from colostrum in the newborn calf. A Fortran program was used to generate plots of the time course of the concentration of colostrum constituents in serum and other body fluids following a single feed of colostrum. These plots show how the changes in serum concentration of absorbed Ig isotypes, gamma-GT and D-xylose are affected by different rates of intestinal absorption, redistribution in body fluids and removal from plasma. A critical examination of data from the computer model and from the calf feeding experiments supports the view that the absorption of IgG1, IgG2 and IgM is not selective in the calf. The data were compared with earlier studies of the efficiency of the colostral transfer of Ig to the calf. In the present study the transfer efficiencies of IgG1, IgG2, IgM, gamma-GT and D xylose were 46 per cent, 49 per cent, 47 per cent, 18 per cent and 21 per cent, respectively. PMID- 2895491 TI - Pathology of the testis in intersex syndromes. AB - This report reviews the pathologic, clinical, and cytogenetic aspects of various forms of male pseudohermaphroditism, mixed gonadal dysgenesis, true hermaphroditism, and Klinefelter's syndrome. PMID- 2895492 TI - Analysis of immunoglobulin heavy chain restriction fragment length polymorphisms in IgA nephropathy. PMID- 2895493 TI - What to expect from the newest drugs. PMID- 2895495 TI - [Reflux esophagitis: therapeutic indications]. PMID- 2895494 TI - [Update on the treatment of purulent ulcero-hemorrhagic rectocolitis]. PMID- 2895497 TI - [Cardiac insufficiency. Current treatment]. PMID- 2895496 TI - [Coronary insufficiency]. PMID- 2895498 TI - Ecstasy returns to Schedule I. PMID- 2895500 TI - [Neuroleptics]. PMID- 2895499 TI - Absence of TGF-beta receptors and growth inhibitory responses in retinoblastoma cells. AB - The responses of retinoblastoma tumor cells and normal retinal cells to various growth inhibitory factors were examined. Whereas fetal retinal cells were highly sensitive to the antimitogenic effects of transforming growth factor beta 1 (TGF beta 1), retinoblastoma tumor cell lines were all resistant to this factor. Binding assays and affinity labeling of these cells with radioiodinated TGF-beta 1 revealed that the cells did not have TGF-beta receptors. The retinoblastoma cells lacked the three affinity-labeled proteins of 65, 95, and 300 kilodaltons typically seen in human cell lines and thus differed from normal retinal cells and from other types of neuroectodermal tumors that display the normal pattern of receptors. Loss of TGF-beta receptors, which is a rare event among tumor cells, may represent one mechanism through which these cells escape from negative control and form retinoblastomas. PMID- 2895501 TI - Effects of SMS 201-995, a somatostatin analogue, on the exocrine pancreatic secretion and gut hormone release in dogs. AB - The effect of SMS 201-995, an analogue of somatostatin, on pancreatic exocrine secretion was investigated in both interdigestive and digestive states in dogs. In four dogs with gastric and Thomas duodenal cannulas, the pancreatic juice was collected by direct cannulation of the main pancreatic duct. SMS 201-995 was infused intravenously at doses of 0, 15, 30, 60, and 120 ng/kg/hr for 2 to 3 hours in the following experimental conditions: (1) interdigestive pancreatic secretion, (2) pancreatic secretion stimulated by the intravenous infusion of both secretin, 0.06 CU/kg/hr, and cholecystokinin octapeptide (CCK8), 0.03 microgram/kg/hr, and (3) pancreatic secretion after ingestion of a test meal. Pancreatic juice was analyzed for volume and outputs of bicarbonate and protein. Plasma levels of motilin, pancreatic polypeptide (PP), CCK, and secretin were determined by radioimmunoassay. SMS 201-995 inhibited significantly the pancreatic secretion and release of hormones, including secretin, CCK, PP, and motilin, in all three experimental conditions. The inhibitory action of SMS 201 995 on pancreatic secretion and hormone releases was dose dependent. PMID- 2895502 TI - Asthma and pregnancy: a prospective study of 198 pregnancies. AB - A study was designed to investigate whether asthma, when carefully managed, is associated with an increased risk of complications in connection with pregnancy. One hundred and eighty one asthmatic women were monitored during 198 pregnancies. Antiasthmatic treatment consisted of inhaled beta 2 adrenergic drugs, beclomethasone, sodium cromoglycate, oral theophylline, and systemic corticosteroids as needed. Postpartum information on asthmatic symptoms and infant feeding was collected by means of a questionnaire. A control group of 198 non-asthmatic pregnant women was matched for age and parity. Atopic women had less severe asthma than non-atopic women. During pregnancy 40% of the patients were managed with the same antiasthmatic medication as before pregnancy; 18% needed less and 42% more medication. Pre-eclampsia occurred more often in asthmatic than control subjects, especially in patients with severe asthma. Hypoglycaemia occurred more often in infants of mothers with severe asthma than in infants of mothers with less severe disease. Theophylline medication at term did not influence labour or delivery. Asthma caused no emergencies during labour. Among the asthmatic subjects 28% of babies were delivered by caesarean section compared with 17% in the control group. There was no difference between asthmatic and control subjects with regard to length of gestation, birth weight, incidence of perinatal deaths, low Apgar scores, neonatal respiratory difficulties, hyperbilirubinaemia, or malformations. It is concluded that severe asthma or systemic corticosteroid treatment (or both) during pregnancy seems to increase the incidence of mild pre-eclampsia in the mother and hypoglycaemia in the infant. The findings suggest that careful supervision of asthma during pregnancy and labour by obstetricians and chest physicians working in close collaboration should prevent most of the serious obstetric and neonatal complications of asthma in pregnancy reported by previous authors. PMID- 2895503 TI - Two genes homologous with human protein S cDNA are located on chromosome 3. AB - A cDNA coding for the carboxy-terminal region of human protein S and containing a complete 3'-untranslated region, was isolated by a combination of antibody screening of a lambda gt11 human liver cDNA expression library and in situ hybridization of a pUC9 human liver cDNA library. Hybridization analysis of human total DNA with radiolabelled non-overlapping cDNA restriction fragments revealed the existence of two genes per haploid genome homologous with the protein S cDNA. Both genes were mapped to chromosome 3 using human-rodent cell hybrids. Neither of the genes showed polymorphism for sixteen different enzymes upon hybridization with the protein S cDNA. PMID- 2895504 TI - [Biological psychiatry. 1) The dopamine-acetylcholine equilibrium model]. PMID- 2895505 TI - [Biological psychiatry. 2. Developments in pharmacotherapy of anxiety, insomnia and stress and in the biological treatments of depression]. PMID- 2895506 TI - Calcium efflux and neurotransmitter release from rat hippocampal synaptosomes exposed to lead. AB - The results of several studies, employing various tissue preparations, have demonstrated that in vitro Pb exposure has similar effects on the release of several different transmitter substances. Pb has been observed to attenuate depolarization-evoked release and increase spontaneous (depolarization independent) release. The current study confirms that Pb in vitro increases the spontaneous release of [3H]acetylcholine (ACh) from superfused synaptosomes prepared from rat hippocampus. Additionally, hippocampal synaptosomes, preloaded with 45Ca, were superfused under conditions similar to those used in the [3H]ACh release studies. Exposure to 1-30 microM Pb produced a concentration-dependent increase in the efflux of 45Ca that was quantitatively and temporally related to the Pb-induced release of [3H]ACh from the hippocampal synaptosomes. Depolarization-evoked [3H]ACh release with high potassium did not produce a corresponding increase in 45Ca efflux. It is concluded that the Pb-induced increase in spontaneous transmitter release is apparently due to either an increase in intraneuronal ionized calcium or the stimulation by Pb of Ca activated molecules mediating transmitter release. PMID- 2895507 TI - Testicular germ cell differentiation. PMID- 2895508 TI - 24xi-Methyl 5 alpha-cholestane-3 alpha,6 beta,9 alpha,25-tetrol 24-monoacetate, a novel polyhydroxylated steroid from the soft coral Sarcophyton tortuosum. AB - A novel polyhydroxylated steroid, named sartortuosterol A, with rare 3 alpha- and 6-hydroxyl groups, was isolated from the South China Sea soft coral Sarcophyton tortuosum Tixier-Durivault, and its structure was established as 24xi-methyl 5 alpha-cholestane-3 alpha, 6 beta, 9 alpha,25-tetrol 25-monoacetate from spectroscopic data and chemical conversions. PMID- 2895509 TI - Different sensitivity to hypoxia in neuronal activities of lateral vestibular and spinal trigeminal nuclei. AB - Electrophysiologic studies were performed to examine the effects of hypoxia on neuronal activities of the lateral vestibular and spinal trigeminal nuclei using rats anesthetized with chloral hydrate. The rats inhaled a gas mixture of 5% oxygen and 95% nitrogen for 3.5 minutes to induce hypoxia, followed by room air. Under these conditions, mean PaO2 was decreased from 85 to 22 mm Hg 3 minutes after the start of the inhalation concomitant with a decrease in blood pressure from 108 to 55 mm Hg. There were no significant differences in these variables between rats used for vestibular nucleus experiments and rats used for trigeminal nucleus experiments. In the lateral vestibular nucleus, hypoxia inhibited postsynaptic components of the evoked field potential, spike generation of monosynaptic neurons on vestibular nerve stimulation, and firing induced by iontophoretic application of glutamate. In the spinal trigeminal nucleus, however, there were no alterations of the field potential or spike generation of the neurons on trigeminal nerve stimulation. These results indicate that the lateral vestibular nucleus neurons are much more sensitive to hypoxia than the spinal trigeminal nucleus neurons. The failure of transmission in the monosynaptic neurons of the lateral vestibular nucleus is suggested to be due to the inhibition of excitability of the postsynaptic membrane. PMID- 2895511 TI - Entamoeba histolytica in inbred mice: evidence of liver involvement. AB - Following observations that certain mouse strains appeared to be susceptible to liver invasion by Entamoeba histolytica, mouse strains CBA/HN, CBA/HN, nu/nu, CBA/HN nu/+, CBA/HN Dh/+, CBA/HN +/+, C3H/HeJ Lps/Lps and AB/H, were infected intra-intestinally with strain SAW 408 (zymodeme II) of the amoeba. A number of mice from each group died during the first 14 days with acute lesions. The remainder were killed at 4 and 6 months after infection. CBA/HN, CBA/HN Dh/+, and CBA/HN +/+ mice all had amoeba-infected livers, although only 2 mice had extensive, typical liver lesions. PMID- 2895510 TI - Serological survey of Prospect Hill virus infection in indigenous wild rodents in the USA. AB - We found serological evidence of infection with Prospect Hill virus, a Hantaan like virus isolated from meadow voles (Microtus pennsylvanicus), in microtine and cricetid rodents trapped in Maryland, West Virginia, Minnesota and California, USA. Fluorescent antibodies were detected in sera from M. pennsylvanicus (74/277), M. californicus (39/185), Clethrionomys gapperi (5/51), Peromyscus maniculatus (4/22) and P. truei (1/11). Sera from seropositive P. maniculatus contained neutralizing antibodies against Prospect Hill virus, confirming that infection with Prospect Hill virus or antigenically related viruses is not restricted to microtine rodents in the USA. Despite the widespread distribution of Prospect Hill virus in indigenous rodents, the recent demonstration that American mammalogists are only rarely infected supports the view that the overall risk of Prospect Hill virus infection in man is low. PMID- 2895512 TI - The effect of orally administered Entamoeba histolytica on Wistar and athymic (rnu rnu) rats observed during a 12-month period. AB - Groups of LacP (Wistar) and rnu rnu athymic rats were dosed orally with cultured trophozoites of 2 strains of Entamoeba histolytica, zymodeme II, and observed for up to 12 months. One group of Wistar rats remained infected but with no apparent disease for 6 months; faecal samples from another became negative after one week. All the athymic rats were still infected at 12 months and amoebae could be cultured from their stools. The effect of even long-term infection was usually only mild erosion of the caecal wall and only 2 rats developed typical chronic lesions and ulcers. Amoebae were isolated in culture from the apparently unaffected livers of 2 rats 12 months after infection. PMID- 2895513 TI - Immunocytochemical detection of Entamoeba histolytica. AB - Human anti-Entamoeba histolytica immunoglobulin was used to detect Entamoeba histolytica in 74 positive samples from several different sources, using an indirect immunoperoxidase method. In 73 samples, the protozoan was easily identified. Trophozoites and cysts of all cultured Entamoeba strains examined were strongly stained, and as few as 3 trophozoites per microscope slide could be detected. In addition, 51 negative control samples were also tested and non specific reactions were not observed. These preliminary results show that this method is both sensitive and specific, and can easily detect trophozoites and cysts of different E. histolytica strains. PMID- 2895514 TI - An enzyme-linked immunosorbent assay for the detection of Entamoeba histolytica antigens in faecal material. AB - This paper describes a method for the detection of Entamoeba histolytica antigens in stool samples using a multi-layer ELISA. The method is sensitive and specific, showing no interference with other intestinal parasites, e.g. E. coli, E. hartmanni, Endolimax nana, Iodamoeba buetschlii, Hymenolepis nana, Giardia lamblia, Trichomonas and Ascaris. The method provides a rapid and simple screening assay for E. histolytica infections and should assist in diagnosis and epidemiological studies of the disease. PMID- 2895515 TI - First human case of haemorrhagic fever with renal syndrome in the Central African Republic. PMID- 2895516 TI - Rift Valley fever virus transmission by different Egyptian mosquito species. AB - 4 Egyptian mosquito species were tested for their ability to transmit the Egyptian ZH-501 strain of Rift Valley fever virus (RVFV) to golden Syrian hamsters. Culex (Cx.) antennatus was the most efficient vector, showing a 37.5% transmission rate following a hamster blood meal containing 10 suckling mouse intracerebral 50% lethal doses (SMILD50) per ml. Fully engorged mosquitoes of this species showed an infection rate of 85% with the mean viral titres of transmitting mosquitoes 100-fold higher than non-transmitters. Autogenous and anautogenous populations of Aedes (Ae.) caspius were tested separately, and the transmission rates were 23.1% and 9.7% respectively, following feeding on hamsters with similar levels of viraemia. Two anopheline species, Anopheles (An.) multicolor and An. pharoensis, showed 12.5% and 3.5% transmission rates under similar conditions. In these 3 species infection rates exceeded 75% and mosquitoes transmitting had a higher average titre than those not transmitting. PMID- 2895518 TI - HTLV-1 and blood transfusion. PMID- 2895517 TI - Prevalence of cytomegalovirus antibody in hemophiliacs and homosexuals infected with human immunodeficiency virus type 1. AB - We determined the prevalence of antibody to cytomegalovirus (CMV) in the sera of non-homosexual hemophilia patients and homosexual men infected with the human immunodeficiency virus type 1 (HIV-1). CMV antibody testing by latex agglutination revealed 33 of 58 HIV-1 infected hemophiliacs (57%) were antibody positive compared with 54 of 54 HIV-1 infected asymptomatic non-hemophiliac homosexuals (100%) (p less than .001). Nine of 15 hemophiliacs (60%) with symptomatic HIV-1 infection were CMV antibody-positive. We also tested 22 HIV-1 antibody-negative hemophiliacs who had received non-heat treated factor concentrates. 14 of these 22 (64%) were CMV antibody-positive compared with 57% of HIV-1 antibody-positive hemophiliacs. We conclude 1) there is little correlation between transmission of HIV-1 and CMV by factor concentrates, 2) the presence of CMV antibody does not appear to be associated with clinical stage of HIV-1 infection in hemophiliacs, and 3) there may be a significant number of CMV antibody-negative hemophiliacs with HIV-1 infection at risk for primary infection and subsequent disease if CMV seronegative blood products are not provided for future transfusions. PMID- 2895519 TI - [Induction of bithorax phenocopies by organic solvents in the early stages of Drosophila embryogenesis]. PMID- 2895520 TI - [Congestan]. PMID- 2895522 TI - [Neuroleptics can also cause rhabdomyolysis]. PMID- 2895521 TI - [Acute pain due to kidney/ureter stones treated with intramuscular Voltaren or Ketogan]. PMID- 2895523 TI - Genetics and expression of the fragile X syndrome. AB - The discovery of the Fragile X (fra(X] syndrome represents a major advance in our understanding of mild mental retardation. This X-linked syndrome is the most common hereditary form of mental retardation. Recent estimates find that approximately 1/981 males and 1/677 females carry the fra(X) chromosome. The majority of affected males are moderate to severely retarded, but about 20% are mildly retarded and about 5% are borderline. Approximately 20% of males who inherit the fra(X) chromosome are termed non-penetrant; they do not express it cytogenetically and are of normal intellect. About 1/3 of carrier females show mental impairment and about 10% are mildly retarded. We have found evidence for genetic heterogeneity based on linkage analysis to flanking DNA probes. Some large families show tight linkage between fra(X) and the flanking probe F9, while others show loose linkage. Preliminary findings indicate the linkage heterogeneity may also be related to cognition: affected males in tightly linked families tended to be mildly retarded. PMID- 2895525 TI - Prenatal factors including fetal alcohol syndrome. AB - The first discovered exogenous teratogen causing mental retardation was rubella embryopathy described in 1940. Later, cytomegalic virus infection and toxoplasmosis during pregnancy and ionogenic radiation has been shown to cause embryofetopathies with concomitant mental retardation. Methyl mercury in high doses cause severe central nervous system pathology in both mothers and their fetuses. The fetal alcohol syndrome is now generally accepted as causing mostly mild mental retardation. Of therapeutic drugs, antiepileptics have been shown to carry a risk for the fetal antiepileptic syndrome complex. We have recently been able to describe fetal pathology following high intake of benzodiazepines during pregnancy. PMID- 2895524 TI - DNA studies of X-linked mental retardation associated with a fragile site at Xq27.3. AB - The fragile-X mental retardation syndrome (FRAX-MR) is one of the most prevalent X-linked diseases. In affected males and in a proportion of carrier females a fragile site at Xq27.3 [fra (X)] is detected when the lymphocytes are cultured under conditions of thymidine deprivation. The fra (X) analysis can be used in the diagnosis of only 56% of carrier females (13, 14) and prenatal diagnosis by this method is not always feasible, thus making genetic counselling of affected families difficult, and sometimes impossible. We have analysed FRAX-MR families using RFLP and four DNA probes from Xq27-Xq28. Estimation of the recombination fraction indicates that the proximal probe F9 is not significantly linked to the FRAX-MR locus while the three distal probes F8, DXS52 and DXS15 show linkage. These probes could be used in the diagnosis of FRAX-MR in those families that do not show evidence for recombination. Used in conjunction with the fra (X) analysis, the segregation studies with these probes should improve the genetic counselling of the FRAX-MR syndrome and should be useful for the genetic and molecular analysis of this unique disease. PMID- 2895526 TI - Pre- and perinatal environmental origin in mild mental retardation. AB - From population-based studies of mild mental retardation made in the beginning of the 1980s in Sweden and covering the birth years 1959-70, data on pre- and perinatal environmental origin have been analysed. Information gathered from these data has also been compiled together with more recent findings from epidemiological studies of other brain impairment groups, in particular cerebral palsy and infantile hydrocephalus. PMID- 2895527 TI - Horseshoe kidney in Russell-Silver syndrome. AB - We describe a case of Russell-Silver syndrome associated with horseshoe kidney in a three-year-eleven-month-old boy. Several urologic anomalies are reported in this syndrome, but to our knowledge, horseshoe kidney has not been reported previously in the English literature. PMID- 2895528 TI - Encephalitis in dogs associated with a batch of canine distemper (Rockborn) vaccine. AB - During a period of seven months in 1982-83 cases of postvaccinal encephalitis were recorded in dogs in various parts of Britain after the administration of a particular batch of combined distemper/hepatitis vaccine. Detailed investigations of one of these cases revealed that the distemper component was responsible and the vaccine virus was recovered from the brain of an affected dog. PMID- 2895529 TI - Syrup of ipecac awareness: the use of a survey to direct future education efforts. AB - Syrup of ipecac awareness has been a major educational endeavor of our poison center for nearly 15 years. Educational efforts have been widespread and not directed specifically at any demographic population. A telephone survey was developed to determine our effectiveness in creating awareness and to identify demographic trends which would direct our future efforts. Respondents were randomly selected from the metropolitan telephone directory. Four hundred surveys were completed. The data was analyzed for statistical significance using chi square. The demographic background of the respondents compared favorably with that published by the Census Bureau. Fifty and six tenths percent were aware of syrup of ipecac. Age groups between 30-59 were more aware of ipecac than younger or older groups. Females were more aware of ipecac than males (37% vs 2%). There was a direct relationship between the number of years of education and ipecac awareness (college 62%, high school 49%, non-high school 37%). Married and divorced respondents had a higher awareness than single individuals (56% vs 38%). Respondents with working spouses had greater awareness than those with unemployed spouses (65% vs 43%). Twenty-four percent claimed to have ipecac in their home at the time of the survey. This provides significant insight for future direction with our educational efforts. PMID- 2895530 TI - Stimulation of cell proliferation in rabbits by MTP-PE, a lipophilic muramyl peptide. AB - The in vivo effect of the lipophilic muramyl peptide MTP-PE on the proliferation of blood cells and various tissues of the rabbit was studied by means of 3H thymidine. Animals were killed up to 120 h after one or two i.v. injections of MTP-PE (10 mg/kg). MTP-PE caused a drastic effect on white blood cells: (1) neutropenia and lymphocytopenia occurring within 5 h was followed by leukocytosis of neutrophils and their juvenile forms by 24 h and thereafter, (2) within 24 h the number of prelabelled, i.e. recently regenerated, mononuclear cells in the bone marrow and the vascular system of various tissues increased approximately threefold, and (3) within 48 h the concentration of proliferating monocytic cells (1-h pulse labelling) rose to maximum levels of up to 20-fold in the lumina of blood vessels, particularly in capillaries of many organs. The number of proliferating cells also increased in the adventitia of medium and small arteries with a maximum at 48 h, whereas this occurred only later in the media and hardly at all in the intima. Thus, these proliferating, apparently monocytic cells are blood derived, and migrate into the tissue within 24 h after MTP-PE administration. In addition, proliferation in the epithelium of the bile ducts and oesophagus was also stimulated with a maximum at 24 h after MTP-PE. In contrast, enhanced proliferation occurred more slowly and to a lesser extent in hepatocytes, hepatic interstitial cells, and renal epithelial cells, consistent with a regenerative process after an inflammatory or toxic event. PMID- 2895531 TI - Immunocytochemical demonstration of peroxisomal enzymes in human kidney biopsies. AB - Peroxisomes are particularly abundant in the proximal tubules of the mammalian kidney. We describe the immunocytochemical localization of catalase and three peroxisomal lipid beta-oxidation enzymes: acyl-CoA oxidase, bifunctional protein (enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase) and 3-ketoacyl-CoA thiolase, in human renal biopsies fixed with glutaraldehyde and embedded in Epon. For light microscopy of semithin sections, satisfactory immunostaining required removal of the resin and controlled proteolytic digestion followed by the indirect immunoperoxidase technique. Brief etching of ultrathin sections with alkoxide followed by the protein A-gold method were used for electron microscopic localization of the enzymes. The immunoreactive peroxisomes were distinctly visualized in proximal tubular epithelial cells with no staining of any other cell organelles. The results establish the presence of catalase and of peroxisomal lipid beta-oxidation system proteins in human kidney. The immunocytochemical procedure described herein provides a simple approach for the investigation of peroxisomal structure and function in human renal biopsies processed for ultrastructural studies. PMID- 2895532 TI - Radioprotection by pretreatment with deuterated water: cytokinetic changes in the small intestine of the mouse. AB - All mice partially deuterated by ingestion of 29% heavy water for 12 days survived whole body gamma irradiation (8.5 Gy) from a 60Co source, whereas 42% of nondeuterated control animals died from bone marrow failure. The incorporation of 3HTdR into enterocytic DNA, as measured by autoradiography and liquid scintillation spectrometry, was used to assess the proliferative activity of small intestinal epithelium. The sequence and the magnitude of changes in tritium activity were in good agreement. Deuteration alone resulted in a reduced proliferative activity of small intestinal crypt epithelium, particularly in the basal cell positions and the first positions of the proliferation compartment. The number of positions occupied by the proliferative compartment and the crypt length were, however, barely affected by deuteration. The radiation-induced depression of DNA synthesis in the proliferative compartment was of similar magnitude in both groups. Crypt epithelium in deuterated mice, however, displayed signs of an accelerated and/or enhanced regeneration. The cytokinetic changes in deuterated animals are consistent with a protective effect for clonogenic intestinal epithelium at the time of irradiation. PMID- 2895533 TI - Interdigitating reticulum cells in lymph nodes of Sezary syndrome. Freeze fracture and ultrathin-section morphology. AB - Lymph nodes with extensive leukemic infiltration from three patients with the Sezary syndrome were examined in ultrathin sections and in freeze-fracture replicas. Sezary cells (SC) and interdigitating reticulum cells (IDC) were the predominant cell types in the lymph nodes. Both were closely connected with each other by apparently interdigitating cytoplasmic processes. The projections between these cells were, in the main, processes from the IDC. In freeze-fracture replicas these cellular processes did not appear as interdigitations but were more bubble-like, and for this reason these cells are imprecisely described by the term "interdigitating." The SC were seen to possess only short cytoplasmic processes. The frequent polar grouping of cell organelles in SC in the region of the contact zone with IDC and the high organelle content of IDC ('activated IDC') could be the morphologic expression of intense interaction between IDC and SC. IDC displayed three features in freeze-fracture which are not specific to the Sezary syndrome, but should be applicable to IDC in general: (1) they exhibited an approximately equal density of intramembrane particles in both the E-face and the P-face, (2) some of the intramembrane particles in the P-face were assembled in clusters and (3) the surface showed bubble-like formations of the cytoplasmic processes. On the basis of these properties it was possible to distinguish IDC from macrophages and lymphocytes in freeze-fracture replicas. PMID- 2895535 TI - In vitro and in vivo elimination of macrophage tumor cells using liposome encapsulated dichloromethylene diphosphonate. AB - It is shown in the present study that RAW 264 tumor cells can be killed by liposome-entrapped dichloromethylene diphosphonate (DMDP), both in vitro and in vivo. DMDP is ingested by phagocytic cells when entrapped in liposomes. Once phagocytized the liposomal membranes are digested and the drug is released into the cell and is ready for action. In vitro, even low doses of liposome-entrapped DMDP caused an significant reduction in cell numbers. In vivo, liposome encapsulated DMDP markedly reduced tumor formation in the liver, when given 1 day after injection of 1 x 10(6) RAW 264 tumor cells. Liposome-encapsulated DMDP, given 4 or more days after injection of the tumor cells had no significant effect. We concluded that tumor formation by RAW 264 cells is only susceptible to in vivo treatment with liposome-entrapped DMDP during a short period of time after injection of the cells. Obviously, phagocytosis of the tumor cells is reduced after this period making the cells less susceptible to treatment with the liposome-entrapped drug. PMID- 2895534 TI - Modification of surfactant metabolizing cells in rat lung by clofibrate, a hypolipidemic peroxisome proliferating agent. Evidence to suggest that clofibrate influences pulmonary surfactant metabolism. AB - The influence of clofibrate (ethyl-alpha-p-chlorophenoxy-isobutyrate), a hypolipidemic peroxisome proliferating agent, has been tested on the lungs of adult male rats. Drug administration for 7 days caused structural changes in two types of lung cells, both of which are involved in the metabolism of the pulmonary surfactant. By light microscopy the prominent features were the presence of enlarged type II alveolar epithelial cells and foamy intraalveolar macrophages. Compared with controls, type II cells in treated rats apparently contained more numerous surfactant-containing lamellar bodies, as visualized in semi-thin sections of Epon-embedded tissue. This difference was quantified morphometrically by light microscopy: the number of lamellar bodies was estimated as the profile number per individual type II alveolar cell, transsected at its nucleus. Clofibrate administration for 7 days resulted in a significant increase in the number of the lamellar inclusions. In contrast the number of type II alveolar cells per area of lung remained unchanged. There was no evidence of atelectasis or inflammatory infiltration in the drug-treated lungs, a finding confirmed in sections of perfusion-fixed, paraffin-embedded whole lung-lobes. By electron microscopy the lamellar inclusion bodies in the type II alveolar cells in treated rats, apart from being more numerous and sometimes smaller, were morphologically identical to those in controls. The vacuolated alveolar macrophages seen in treated rats also contained various lamellar phospholipid inclusions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2895536 TI - Reduction in phosphoenolpyruvate carboxykinase in rat liver parenchymal cells following experimentally induced cholestasis. AB - The effect of experimentally induced cholestasis on the amount of phosphoenolpyruvate carboxykinase (PEPCK) was studied immunohistochemically in rat liver parenchyma. In control liver, the enzyme was mainly localized periportally and, although the enzyme content was much reduced, this distribution pattern was maintained up to 2 weeks after ligation of the common bile duct. At 4 and 8 weeks after ligation the enzyme content in parenchymal cells remained low, but became distributed homogeneously throughout the liver parenchyma. This suggests that after bile duct ligation, gluconeogenesis from lactate is impaired. This may well be the cause of the adaptive changes to enhance the glycogenolytic capacity of parenchymal cells to maintain as far as possible a constant blood glucose level. PMID- 2895537 TI - Oncogene expression in a medullary thyroid carcinoma. AB - We report the expression of Ha-ras, fos, c-myc and N-myc mRNA in a human medullary carcinoma of the thyroid gland, both in primary tumor and lymph node metastasis, as demonstrated by in situ hybridization and Northern blot analysis. A significant difference in the oncogene expression in the primary tumor and the metastasis was not observed. Tumor tissue revealed a significant overexpression of Ha-ras, c-myc and N-myc mRNA as compared to the normal thyroid gland. The amount of fos mRNA expression in non tumorous thyroid gland did not significantly differ from tumor tissue, sis, fms and abl mRNA expression was not detectable in tumor tissue and non tumorous thyroid gland. We conclude, that the (over)expression of the oncogenes Ha-ras, c-myc and N-myc may be associated with initiation and progression of medullary thyroid carcinoma. Similar studies on additional cases of human medullary thyroid carcinoma will be necessary to reveal further information. PMID- 2895538 TI - Rat or murine colonic carcinomas? M.A.L. Maley et al. versus C.D. Gerharz. PMID- 2895539 TI - DNA flow cytometry in metastases and a recurrency of malignant melanomas. A comparison of results from fresh and paraffin embedded material. AB - Single cell suspensions from 16 biopsies from 15 patients with metastatic or recurrent malignant melanoma were prepared according to the method described by Vindelov (1977) and the nuclear DNA content was measured by a laboratory-built flow cytometer. The DNA histograms thus obtained were compared with those obtained from suspensions of single nuclei from the same biopsies after formalin fixation and paraffin embedding, according to the method of Hedley et al. (1983). Linear regression analysis of ploidy values from fresh material compared with those from paraffin blocks showed a strong correlation (R2 = 0.85), while that of the S-phase fraction was somewhat weaker (R2 = 0.66). It is concluded that archival wax preparations of malignant melanoma cell populations are suitable for FCM analysis of ploidy, and to a lesser extent for analysis of fraction of cells in various cell cycle phases. PMID- 2895540 TI - In vivo growth kinetics of P388 and L1210 leukemias. AB - The P388 lymphocytic leukemia and the L1210 lymphoid leukemia are used as test systems for putative cytotoxic drugs. These leukemias are also used to investigate the perturbation of cell cycle progression of various chemical compounds in more detail. There is little information on the normal growth kinetics in vivo of these leukemias. In the present report we therefore present the results from growth kinetic studies of P388 and L1210 leukemic cells growing in ascites form in mice. We used 3H-TdR autoradiography, DNA flow cytometry and the stathmokinetic method. During exponential growth both leukemias showed a growth fraction of unity. Whereas no significant cell loss was observed during the early growth phase of P388 cells, cell loss was indicated by a discrepancy between potential and actual doubling times during exponential growth of L1210 cells. During the phase of growth retardation, the proportion of G1 and G2 cells increased at the expence of a reduced S phase fraction in the P388 leukemia, whereas only small changes in cell cycle distributions were seen with time after inoculation of L1210 cells. An increasing discrepancy in the reduction of the S phase fraction and the 3H-TdRLI was seen in the P388 cells with time after inoculation. Thus, a majority of P388 cells with S phase DNA content were unlabelled during the late phase of growth restriction, indicating resting cells in S phase. A good correlation was found between the 3H-TdR LI and S phase fraction throughout the life history of L1210 cells, revealing considerable differences in in vivo growth kinetics between the two leukemias. Such differences should be considered when evaluating test results. PMID- 2895541 TI - Thyroid medullary carcinoma of the Djungarian hamster Phodopus sungorus. Ultrastructural evidence for the production of normal and atypical intracellular granules. AB - We have carried out an electron microscopic and immunocytochemical study of thyroid medullary carcinoma arising spontaneously in the Djungarian hamster, Phodopus sungorus. At the ultrastructural level the cytoplasm of tumor cells contained numerous round to slightly elongated, dense-cored secretory granules. The number of secretory granules differed from cell to cell in the tumor, being scanty in some cells but more or less abundant in most. Electron microscopic immunocytochemistry demonstrated that all dense-cored secretory granules in all tumor cells exhibited calcitonin immunoreactivity. In approximately 10% of the tumor cells, unusual star-shaped secretory vesicles were also found in the cytoplasm. These vesicles contained a small, but well-defined, lucent core surrounded by a region of finely granular material of greater electron density. The outer contour of these unusual vesicles was stellate rather than smooth. They appeared to originate not from the Golgi complex, but from the rough endoplasmic reticulum. These atypical stellate vesicles did not show any calcitonin immunoreactivity. Furthermore, in a small number of tumor cells (approximately 1%) a third type of membrane enclosed structure was found. These were conspicuous rods 1-5 micron in length with tapering ends and a crystalline substructure. The presence of both normal and atypical secretory granules in some tumor cells suggests that carcinogenic transformation may interfere with the normal synthesis and assembly of secretory products by the cell. PMID- 2895542 TI - Microenvironment of thymic myoid cells in myasthenia gravis. AB - The microenvironment of myoid cells (MyCs) was studied in myasthenia gravis (MG) thymitis with lymphoid follicular hyperplasia (LFH) (nine cases) and with diffuse B cell infiltration (one case), and compared with findings in the thymuses of non myasthenic control subjects (ten cases). Double immunostaining was used to demonstrate MyCs labelled by anti-desmin together with other thymic components such as keratin-positive epithelial cells, Ki-M 1-positive interdigitating reticulum cells (IDCs), Ki-M 4-positive follicular dendritic reticulum cells, Ki M 6-positive macrophages, CD22-positive B-cells, CD1-positive cells, CD3-positive T-cells or HLA-DR-positive cells. Round or elongated MyCs were confined to the thymic medulla and were surrounded by CD3-positive T-cells and CD22-positive B cells. In MG thymitis MyCs were localized in the vicinity of, but not inside germinal centres (GCs). MyCs were always HLA-DR-negative, but were invariably embedded in a cellular micromilieu with strong HLA-DR expression. A remarkable feature of MG thymitis was that the great majority of MyCs were in intimate contact with intramedullary IDCs. Morphometric studies confirmed that such contacts were significantly less frequent in thymuses from non-myasthenic subjects. This indicates that an IDC-dependent antigen-presenting process for T cells may actively involve MyCs in MG thymitis. PMID- 2895543 TI - Effects of bile acids and endotoxin on the function and morphology of cultured hamster Kupffer cells. AB - The mechanisms of hepatic reticuloendothelial cell dysfunction in obstructive jaundice were investigated using cultured hamster Kupffer cells. The introduction of free bile acids, cholic acid (CA) at concentrations over 2 mM and chenodeoxycholic acid (CDCA) over 1 mM inhibited colloidal carbon pinocytosis. CA and CDCA at concentrations over 0.5 mM inhibited IgG-coated sheep red blood cell phagocytosis. With the application of conjugated bile acid and endotoxin at concentrations over 50 micrograms/ml, endocytic function was inhibited. With bile acids, a dose-dependent increase in the concentration of beta-glucuronidase occurred in the culture medium, and with endotoxin a time-dependent increase in beta-glucuronidase was noted. Bile acids produced alterations in cell organelles before destruction of the cell membrane. The presence of endotoxin led to the appearance of large vacuoles in the cytoplasm. These observations suggest that bile acids and endotoxin inhibit Kupffer cells by different mechanisms. We tentatively conclude that bile acids rather than endotoxin influence Kupffer cells in vivo. PMID- 2895544 TI - Stress-induced blocking of cell division in the colchicine arrest technique. AB - Previous studies have shown that procedures commonly used in studies of cell population kinetics in laboratory animals cause a transient block of the entrance of cells into mitosis. The purpose of the present study was, therefore, to examine whether the handling of animals in conjunction with the administration of colchicine affects the results obtained by the metaphase arrest technique. Groups of rats were injected with colchicine or saline at 1300 h and sacrificed at regular intervals during the following 140 min. Histological sections of the palatal mucosa were produced and the number of metaphases was assessed in the epithelium. In both the saline-treated and colchicine-treated groups the numbers of metaphases decreased immediately after injection and reached a minimum within 30 min. After that time a transient increase was observed in the saline group, whereas the number of metaphases in the colchicine-treated group increased continuously during the experimental period. These results indicate that colchicine takes effect after a delay period of 30 min and that the handling procedures in conjunction with the administration of colchicine provoke a transient block of the entry of cells into mitosis. The second part of the study was designed in such a way that the number of metaphases collected during a 2 h period under the influence of stress induced by injection of colchicine could be compared with the number of metaphases collected during the same time period without the influence of stress.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2895545 TI - [Intravenous administration of trimepranol--clinical electrophysiology]. PMID- 2895546 TI - [Structural characteristics of the testes and their adnexa in false cryptorchism]. PMID- 2895548 TI - Pharmacokinetic and pharmacodynamic modelling of the alpha adrenoceptor antagonist doxazosin. AB - 1. The pharmacokinetic and pharmacodynamic profiles of intravenous and oral doxazosin were investigated in 6 normotensive volunteers. 2. The pharmacokinetics of i.v. and oral doxazosin were fitted simultaneously and independently. The parameters derived were in good agreement with a mean elimination half-life of 539 +/- 75 min, bioavailability of 0.65 +/- 0.11 and clearance of 140 +/- 26 ml/min. 3. Pharmacokinetic-pharmacodynamic modelling indicated that the sensitivities to oral and i.v. doxazosin in individual subjects were in good agreement. 4. Based on these findings it is unlikely that doxazosin metabolites contribute significantly to the pharmacodynamic profile of doxazosin. PMID- 2895547 TI - [Detection of natural foci of hemorrhagic fever with renal syndrome in the territory of Crimean and Chernigov Provinces]. PMID- 2895549 TI - [Injuries caused by stingrays]. AB - We report on an injury caused by the bite of a South American freshwater stingray. Although wide excision is the therapy of choice, prolonged healing must be expected. We give some information on the mode of injury and biological data regarding the genus protamotrygon. This stingray may also be bred in aquariums. PMID- 2895550 TI - [Metaconceptual developments: hierarchical classification of unknown numbers of objects as a criterion for understanding class inclusion]. PMID- 2895551 TI - [Multifactorial relations of critical flicker fusion frequency (CFF)--correlation of the effect with physical and physiologic parameters]. PMID- 2895552 TI - [Max Wertheimer in Frankfurt--on the beginnings and developmental crisis of Gestalt psychology. Initial studies of motion perception (1910-1912)]. PMID- 2895553 TI - [The life and work of David Katz (1884-1953)]. PMID- 2895554 TI - [Max Wertheimer in Frankfurt--on the beginnings and developmental crisis of Gestalt psychology. II. Structural rules of motion and space perception (1911 1914)]. PMID- 2895555 TI - Clostridial cystitis in a nondiabetic man: case report. PMID- 2895556 TI - Emergency drug supplies. PMID- 2895557 TI - [Physicochemical and immunobiological properties of the dialysate antigen of Bordetella pertussis]. AB - The study of the physicochemical and immunobiological properties of B. pertussis dialysate antigen indicates that the antigen has a complex composition and possesses hemagglutinating and lymphocytosis-promoting activity, which permits further studies with a view to developing diagnostic and prophylactic preparations on the basis of this antigen. PMID- 2895558 TI - The effect of antihistamines and indomethacin on microvascular permeability changes due to repeated pressure-induced local ischemia. AB - Indomethacin can reduce the microvascular permeability induced by repeated ischemia. In this investigation the influence of histamine H1 and H2 receptor blockers was studied for comparison with indomethacin. Application of 60 mmHg pressure to the hamster cheek pouch for 5 min was repeated eight times, with 10 min restitution intervals. Altered permeability was evaluated with use of FITC dextran and intravital microscopy. Progressive efflux of FITC-dextran was observed in the control group. When either diphenhydramine or indomethacin was used alone, a few spots of extravasated dye were seen. Combination of diphenhydramine with either indomethacin or cimetidine reduced the extravasation. Furthermore, the spots appeared significantly later than in the controls, and some faded. Increase in the efflux of macromolecules due to repeated ischemia seems to be mediated via H1 and H2 receptors in conjunction with other receptors and/or amines e.g. prostaglandins. PMID- 2895559 TI - Serum gastrin, insulin and somatostatin levels in normal and obese subjects before and after gastric banding. AB - The postprandial secretion of insulin, gastrin and somatostatin was studied in 23 extremely obese subjects and nine normal-weight controls after a liquid test meal. Apart from a significantly higher insulin level in the obese group, no significant intergroup difference was found. The effect of weight loss on the same hormones was studied in 18 patients 6 months after gastric banding. The mean weight loss during this period was 33 +/- 2.1 (SEM) kg. There was significant decrease in postprandial insulin secretion after gastric banding, but neither gastrin nor somatostatin levels were altered. PMID- 2895560 TI - [Clinicopathological studies of chest x-ray findings in 54 adult T-cell leukemia patients]. PMID- 2895561 TI - Clinical study on the serum levels of immunosuppressive acidic protein in patients with adult T-cell leukemia. AB - Serum levels of immunosuppressive acidic protein (IAP) were measured in patients with adult T-cell leukemia (ATL) in order to clarify its significance in this disease. The mean levels in patients with both acute (854 +/- 404 micrograms/ml) and chronic ATL (439 +/- 103 micrograms/ml) were significantly higher than in sera of healthy controls (367 +/- 104 micrograms/ml). However, mean levels in patients with smoldering ATL, healthy T-cell lymphotropic virus type 1 (HTLV-1) carriers and healthy controls showed no differences. Levels in crisis in chronic and smoldering ATL were similar to those in patients with acute ATL. Serial measurements of serum IAP in a number of patients revealed that the levels reflected each patient's clinical course, suggesting a potential for use in evaluating the effects of chemotherapy. PMID- 2895562 TI - [A case of retentio testis in advanced age with a severed epididymis]. PMID- 2895563 TI - [Clinical evaluation of analgesics in surgical patients in the postoperative period]. PMID- 2895564 TI - Anti-anginal efficacy of a controlled-release formulation of isosorbide-5 mononitrate once daily in angina patients on chronic beta-blockade. AB - The anti-anginal effect of a controlled-release (Durules) formulation of isosorbide-5-mononitrate (5-ISMN) 60 mg, Imdur, once daily was evaluated in a randomised double-blind, placebo-controlled, crossover study with a placebo run in period. Each period lasted for 2 weeks. A total of 70 patients (58 men and 12 women) with stable exertional angina pectoris on beta-blockade, mean age 59 years (range 39-71), were included. Exercise testing was performed on a bicycle ergometer 3 hours after the dose at the end of each period. Anginal attacks and intake of sublingual nitroglycerin tablets were noted. Imdur in combination with a beta-blocker significantly increased the total exercise capacity, the time and total work until the onset of chest pain and at 1 mm ST-depression compared with beta-blockade alone. The attack rate and the nitroglycerin consumption were significantly decreased. Headache was the only significant side-effect. In conclusion, the addition of Imdur once daily to beta-blockade significantly increased the anti-anginal effect. PMID- 2895565 TI - Comparison of motor cortex-induced flexor muscle activity inhibition by hard pressure on various parts of the body and by light pinch of abdomen of animals with gastro-duodenal ulcers. AB - The flexsor muscle electromyogram (EMG) of the upper extremities in response to the motor cortex stimulation was inhibited by hard hand pressure on base of the ear lobe and lumbar perivertebral region and by electrical stimulation of these regions. Similar inhibition was produced by electrical stimulation around the brachium conjuctivum and locus coeruleus (BC-LC) and the reticulogigantocellular nucleus (NRGC). Inhibition of the flexor muscle EMG due to hard pressure on the body parts was abolished by electrical lesioning of the BC-LC and NRGC. The light pinch with hand on the restricted abdominal region did not inhibit the flexor muscle EMG induced by the motor cortex stimulation in normal condition, while such stimulation inhibited the flexor muscle EMG in the ulcer suffering animals after treatment with cysteamine. This inhibition was not influenced by destruction of the NRGC. From these results, it was concluded that inhibition of the motor cortex induced-flexor muscle activities caused by light pinch stimulation of the restricted abdominal region, as the model of the voluntary finger flexion inhibition in O-ring test, was produced by spinal reflex inhibition. PMID- 2895566 TI - Attenuation of tourniquet-induced pain in man by D-phenylalanine, a putative inhibitor of enkephalin degradation. AB - The effect D-phenylalanine (DPA), a putative inhibitor of enkephalin degradation, on the two separate pain components produced by the submaximal effort tourniquet test was evaluated in healthy human volunteers (N = 8). DPA attenuated the increase of the intensity of the ischemic and pressure pain components with increasing ischemia duration, but only the effect on the pressure pain component was significant. The results support some earlier reports suggesting that DPA has analgetic properties. PMID- 2895567 TI - Simple and quick gastric cancer screening method using the "Bi-Digital O-Ring Test" and its critical evaluation by standard X-ray, gastroscopic and pathological microscopic examination. AB - The simple, quick and non-invasive application of the "Bi-Digital O-Ring Test Cancer Screening Method" for adenocarcinoma of the stomach originally described by Y. Omura, indicated 21 out of 196 randomly selected patients who visited our hospital (114 male and 82 female with an average age of 57.2 years) to have a cancer positive response regardless of their original chief complaint. In all these 21 patients we did imaging of the outline of the stomach and localized adenocarcinoma positive area with the "Bi-Digital O-Ring Test Imaging Method." 5 out of 21 patients were confirmed to have adenocarcinoma of the stomach by microscopic examination of biopsied stomach tissue following X-ray and gastroscopic examination. Of these 5 patients with the cancer, 3 had no chief complaint indicative of stomach problems. This study indicated that simple, quick and non-invasive cancer screening method using "Bi-Digital O-Ring Test" with microscopic slide of adenocarcinoma of stomach as reference control substance, can detect stomach cancer with much greater accuracy, without giving any physical discomfort to the patient and with minimum time and expense, compared with well established standard x-ray and gastroscopic examination methods. The effectiveness and relative accuracy of mass screening of patients for gastric cancers using "Bi-Digital O-Ring Test" was well established by this study. PMID- 2895569 TI - Abstracts and short papers of the 3rd International Symposium on Acupuncture & Electro-therapeutics. New York City, October 8-11, 1987. PMID- 2895568 TI - Basic electrical parameters for safe and effective electro-therapeutics [electro acupuncture, TES, TENMS (or TEMS), TENS and electro-magnetic field stimulation with or without drug field] for pain, neuromuscular skeletal problems, and circulatory disturbances. AB - Using voltage-time-dependent negative resistance characteristics of Voltage Current curves of excitable cell membranes estimated without using artificial voltage clamp method, the author made a quantitative analysis of excitability of cell membranes and different conditions of transmembrane action potentials as a bias voltage to the negative resistance of the excitable cell membrane. The pacemaker cells were classified as "Astable Oscillators" and nonpacemaker excitable cells as "Monostable Oscillators," and application of a rapidly changing electromagnetic field to the cells was analyzed as a means of stimulating the cells. The understanding of the 10 essential electrical parameters is highly desirable for safe and effective electrical stimulation. Among these, emphasis was placed on the often neglected, important electrical parameters of "output impedance" of stimulation pulse wave complexes for + and - polarity components, as well as the importance of capacitive current (Ic = C.dV/dt) which depends on rise time as well as fall time of the stimulation pulse wave, and undesirable side effects of electrolysis phenomena due to excessive D.C. current. The difference and similarity between TENS (Transcutaneous Nerve Stimulation) and TES (Transcutaneous Electrical Stimulation), TENMS (Transcutaneous Electrical Nerve and Muscle Stimulation) or TMS (Transcutaneous Muscle Stimulation) was discussed. The author's clinical study indicated that effective TES (TENMS)--characterized by effective muscle contraction without creating pain with a pulse repetition rate approximately the same as the heart rate of the individual--can often give superior beneficial effects in improvement of micro-circulation and subsequent relief of pain and other symptoms compared with TENS that creates stimulation of large diameter sensory nerve fibers without creating significant muscle contraction. Such improvement is often accompanied by the abolishment of the pain with disappearance of local substance P and increase in local serotonin with disappearance of local L-tryptophan. PMID- 2895571 TI - Beta-agonist-induced tachyphylaxis in mouse skin. PMID- 2895570 TI - Effects of dietary poly-unsaturated fatty acids on tracheal histaminergic and cholinergic responsiveness in experimental models of bronchial hypersensitivity and hyperreactivity. AB - Respiratory histaminergic and cholinergic receptor function was investigated in isolated tracheal spirals of guinea pigs receiving different diets. Comparison was made between saline treated (controls) and Haemophilus influenzae treated animals in non sensitized conditions, the latter being a model for bronchial hyperreactivity, and in sensitized conditions, being a model for allergen induced bronchial hypersensitivity. The different semi-synthetic diets (35 energy% fat), varying in linoleic acid content (5.85, 11.25 and 22.05 en% fat) and one diet with low linoleic acid (3.55 en%) in which linolenic acid was added additionally (5.30 en%), exerted profound effects on tracheal reactivity to histamine. In sensitized animals the maximal induced histamine contraction was significantly diminished in the dietary group receiving 5.85 en% linoleic acid as compared with the other dietary groups (35% decrease in the H. influenzae-treated, 20-30% decrease in saline treated animals). Results in non-sensitized animals were similar, though less pronounced. No effect on food intake or growth of the animals could be demonstrated during the six week experimental periods. The carbachol induced contraction of the tracheal spirals of sensitized animals receiving low linoleic acid was also significantly decreased as compared to the other dietary groups (30% for saline treated and 20-30% for H. influenzae-treated animals). No difference in carbachol responsiveness could be detected between the different dietary groups under non-sensitized conditions. The results are discussed in view of the current concepts for bronchial hyperreactivity, especially in relation to eicosanoid involvement. PMID- 2895572 TI - [Study of gamma-GTP activity in urine and renal tissue of experimental warm ischemic kidney]. AB - The acute changes of proximal tubule function and its pathological condition were investigated by measuring (gamma-GTP) activities in the urine and renal tissue using warm ischemic kidneys of adult dogs (n = 34). Eight kidneys were kept in a warm ischemic condition throughout the experimental period and the tissue was extirpated from the kidney at every hour, and 31 kidneys were released from the 30 min ischemic condition. The urine and the blood (peripheral and renal artery and vein) were collected from these kidneys at every hour up to 5 hr. The kidneys observed for urine outflow (n = 24) were divided into three groups with time; 7 kidneys (1 hr), 5 kidneys (3 hr), and 12 kidneys (5 hr), and they were extracted. The gamma-GTP activity of the urine showed the maximum value of 851 +/- 102 mIU/ml at 30 min and decreased to 217 +/- 56 mIU/ml, which declined to be close to the starting value of 133 +/- 26 mIU/ml, at 5 hr after the warm ischemic condition was released. The gamma-GTP activities of the cortex were 325 +/- 62 mIU/mg.p (1 hr), 527 +/- 37 mIU/mg.p (3 hr), and 266 +/- 44 mIU/mg.p (5 hr). However, no increase in gamma-GTP activity was observed either in the renal vein blood, or in the cortex obtained from the 8 kidneys kept in the warm ischemic condition. A histopathological examination showed the progressive changes in some parts of the proximal tubules after release from the ischemic condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2895573 TI - [Relation of enzyme distribution in the kidney and increase pattern of urinary N acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma-GTP) activities following CDDP administration]. AB - Nephrotoxicity is the major side effect of CDDP and it develops renal tubular damage. In the present paper, we have studied acute effects of cis dichlorodiamine platinum (CDDP, 20 mg daily for 5 days) on the renal tubule using urinary NAG and gamma-glutamyltranspeptidase (gamma-GTP) activities as indicators of the toxicity. Altogether 25 courses of chemotherapy in 15 patients who had malignant tumors were studied. Urinary enzyme activities consisting of N-acetyl beta-D-glucosaminidase (NAG, lysosomal enzyme) and gamma-GTP (brush border enzyme) were measured for 11 days from the day before CDDP administration. In all cases, both urinary enzyme activities increased with CDDP administration. The increase of NAG activity was transient; the highest level was detected on the 5th day of chemotherapy and decreased after that. On the other hand, two peaks of gamma-GTP activity were observed in many cases, the first peak during chemotherapy and the second peak soon after the completion of CDDP administration. The differences in increase pattern of these two urinary enzyme activities, suggest that changes of brush border occur in an early stage and cellular tissue including lysosome of renal tubule is impaired afterwards. PMID- 2895574 TI - [A case of leprechaunism with cryptorchidism]. AB - A 6-year-old boy whose chief complaint was right undescended testis was referred to our clinic. He had mental retardation, prominent and widely spaced eyes, large and low-set ears, micrognathia, hyperpigmentation and enlarged genitalia. Therefore, he was diagnosed to have Leprechaunism. Leprechaunism is rare and few studies dealing with this disease have been reported in Japan. With a review of the literature, we briefly discuss about the clinical features of Leprechaunism. PMID- 2895575 TI - Pollinosis: some immunologic and regional considerations and the description of Melia azedarach respiratory allergy. AB - Pollens constitute one of the most allergenic groups for man. Their prevalence make them an important factor when studying antigens that induce allergical diseases such as rhinitis, asthma, conjunctivitis, etc., wherein immunological mechanisms play a fundamental role. It is believed that genetic factors are involved in pollinosis and this could probably explain the enhanced susceptibility of certain individuals to acquire this type of allergy. Here we mention the HLA system, among others involved. Ecological aspects of each region must be carefully evaluated because of the importance of detecting the specific pollen area and the pollen's behaviour which, in turn, will permit an accurate etiological diagnosis. We have investigated a pollen widely spread in our province, called Melia azedarach and have demonstrated its property of inducing allergic respiratory disease. Finally, therapeutics in pollinosis is discussed and attention is paid to drugs such as antihistamines, ketotifen, among others but we think that specific immunotherapy plays a most important role. PMID- 2895576 TI - Beta-blocker therapy in patients with ventricular tachyarrhythmias in the setting of left ventricular dysfunction. AB - Although several studies suggest beta blockers (BB) are effective in suppressing ventricular arrhythmias, less is known about their role in the treatment of patients with ventricular tachyarrhythmias associated with impaired left ventricular function. To assess the tolerance and efficacy of these agents, 32 patients presenting with either ventricular fibrillation (18) or sustained ventricular tachycardia (14) were studied during BB therapy. Left ventricular dysfunction (mean ejection fraction 29%) was present as a consequence of coronary artery disease (26) or cardiomyopathy (6). Baseline arrhythmia assessment revealed recurrent ventricular tachycardia in all patients. Antiarrhythmic drug therapy including BB was guided by programmed stimulation (10), exercise testing (8), ambulatory monitoring (12), or was given empirically (2). Beta blockers were well tolerated, as measured by exercise duration, which improved significantly, and by long-term maintenance, which continued in 23 of 32 (72%) patients. Over a mean follow-up of 668 days, patients treated with BB had a relatively low incidence of both sudden (3%) and nonsudden (9%) death. Thus, BB can be effective and well tolerated adjunct therapy in patients with a history of ventricular tachyarrhythmias in the setting of impaired left ventricular function. PMID- 2895577 TI - Comparison of the antihypertensive effects of betaxolol to atenolol. AB - A randomized double-blind multicenter study compared a new oral beta 1-adrenergic antagonist, betaxolol 10 to 40 mg (n = 71), with atenolol 25 to 100 mg (n = 75). Each drug was administered once daily for 24 weeks in patients with mild to moderate hypertension. Blood pressure (BP) measurements were taken 24 hours after dosing. Each drug produced significant (p less than 0.01) reductions in mean supine diastolic BP. The mean decrease in supine diastolic BP with betaxolol was significantly greater at weeks 4, 6, 10 and 12 (p less than 0.05). Throughout the remainder of the trial (weeks 14 to 24), no significant differences in BP reduction were noted between treatment groups. Normotension (supine diastolic BP less than or equal to 90 mm Hg) was achieved in 72% of those given betaxolol compared with 52% of those given atenolol (p less than 0.05). The most common side effects noted were bradycardia, fatigue and headache. The incidence of these and of central nervous system side effects was similar between the betaxolol and atenolol groups. Both agents were well tolerated. At recommended doses, betaxolol once daily may be more effective than atenolol once daily in patients with mild to moderate hypertension. PMID- 2895578 TI - Decreased heart rate variability and beta blockers after acute myocardial infarction. PMID- 2895579 TI - Incidence and geographic distribution of serologically verified cases of nephropathia epidemica in Sweden. AB - A nationwide survey of hospitalized, serologically verified adult nephropathia epidemica cases in Sweden from 1978 to 1981 was performed. Serum was collected from 1,063 patients with a diagnosis of nephropathia epidemica or one of 10 other renal diseases with related symptoms. Sera were analyzed by indirect immunofluorescence technique for the presence of immunoglobulin G antibodies to Hantaan virus, causative agent of Korean hemorrhagic fever that cross-reacts with the nephropathia epidemica agent. Antibodies were present in 368 patients, 355 of whom also fulfilled four or more of six criteria for clinical diagnosis of nephropathia epidemica. The male:female ratio was 2.7:1. The total number of cases in Sweden varied between 26 and 144 per year, which coincided with the fluctuations in small rodent populations. The highest incidence was found in Vasterbotten County, with a maximum crude incidence rate of 23.5 cases per 100,000 inhabitants per year. Mean crude incidence in Sweden during the study period was 1.3 cases per 100,000 inhabitants per year. The southernmost cases lived in proximity to the 59th parallel. Thus, nephropathia epidemica was found to be prevalent south of the 60th parallel, which was previously assumed to be its southern boundary. PMID- 2895580 TI - Lack of evidence of circulating retroviral antibodies in patients with classic Hodgkin's disease. AB - Because of the T-cell abnormalities observed in Hodgkin's disease and the growing number of Hodgkin's disease cases observed in association with the acquired immunodeficiency syndrome (AIDS), concern has been expressed that a retrovirus may be the primary cause of Hodgkin's disease. We examined plasma specimens from 17 patients with Hodgkin's disease that were drawn in 1979. Because serum containing antibodies to either human T-lymphotropic virus type I (HTLV-I) or HTLV-II precipitate the major core protein, p24, of HTLV-I, lack of reactivity to HTLV-I p24 in all the specimens demonstrated absence of antibodies to HTLV-I or II. None of the specimens was reactive to human immunodeficiency virus type 1 (HIV-1) by ELISA. None of the specimens were reactive on Western blot assays for HTLV-I or -II or HIV-1. Lack of evidence of cross-reacting antibodies to prototype strains of those retroviruses in specimens drawn before the AIDS epidemic suggests that classic Hodgkin's disease is not the result of infection with one of the known human lymphocytotropic retroviruses or a closely related agent. PMID- 2895581 TI - Restriction fragment length polymorphism in the interzeta hypervariable region for prenatal diagnosis of non-deletion alpha thalassemia. AB - A Bam HI restriction fragment length polymorphism in the interzeta hypervariable region (IZ HVR) of the zeta-alpha gene cluster was used for the prenatal diagnosis of a pregnancy at risk for Hb H hydrops fetalis. The parents had zeta alpha thalassemia 1 and non-deletion alpha thalassemia, respectively, and a previous hydrops was missed using the conventional method of gene detection. In this prenatal diagnosis, linkage to IZ HVR was used to exclude non-deletion alpha thalassemia, and the numbers of zeta and alpha genes in the fetus were quantitated to predict the exact genotype. Confirmation was made by analysis of cord blood at delivery. PMID- 2895582 TI - The first report of familial adult T-cell leukemia lymphoma in the United States. AB - Two patients, a daughter and her father, developed the acute type of adult T-cell leukemia/lymphoma (ATLL) within a 3-month period. Antibodies against HTLV-I have been found in both wives of the father. The second wife acquired the infection from her husband within 3 years of marriage. The patients described represent the first cases of familial ATLL in the United States. ATLL continues to be frequently misdiagnosed in the United States. A positive family history consistent with this disease in a patient with a lymphoid malignancy may be a helpful clue for earlier diagnosis. PMID- 2895583 TI - A comparative evaluation of the transport of H2-receptor antagonists by the human and baboon placenta. AB - Using a single cotyledon perfusion model, the placental transport of four H2 receptor antagonists, cimetidine, famotidine, nizatidine, and ranitidine, was determined and compared using normal term human and normal preterm baboon placentas. In both the human and baboon placentas, the transport of each agent was similar whether administered singly or in combination with the other drugs. Drug transport was the same in both directions, maternal-to-fetal and vice versa, indicating a lack of preferential transfer. The H2-receptor antagonists were transported at about 40% the rate of the freely diffusable reference compound, antipyrine. There were no significant differences between the human and baboon in any of the parameters of placental function evaluated. Placental glucose and oxygen consumptions, and lactate production were comparable in the human and baboon preparations. The transport and clearance of each of the H2-antagonists were similar in each species. PMID- 2895584 TI - A grandpaternally derived de novo deletion within Xp21 initially presenting in carrier females diagnosed as Kugelberg-Welander syndrome. AB - We report on two sisters with a history of muscle weakness and an electromyogram (EMG) diagnosis of Kugelberg-Welander syndrome (KWS) or juvenile spinal muscular atrophy. A half-brother to these women was diagnosed to have Duchenne muscular dystrophy (DMD). Using molecular probes, we identified a deletion within Xp21 in this isolated case of DMD. Sequences detected by pXJ1.1 are deleted, while fragments detected by pERT87 are intact. Both of these probes are derived from the DMD locus. We have shown that the affected sisters share with their half brother DNA markers that are linked to the DMD gene and inherited from their maternal grandfather. Dosage analysis of Southern blots show monosomy for pXJ1.1, which has allowed us to determine carrier status within this family and to show that the half-sisters are manifesting DMD carriers. PMID- 2895585 TI - Hyperglycemia induced by electrical stimulation of lateral part of dorsal parabrachial nucleus. AB - Electrical stimulation of the lateral part of the dorsal parabrachial nucleus (PBD) induces hyperglycemia by enhancing glucagon secretion and suppressing insulin secretion in rats. The mechanism of this effect in the light period was examined by use of blockers of the autonomic nervous system. Hexamethonium, a ganglion blocker, and propranolol, a beta-adrenergic blocker, markedly inhibited the hyperglycemic response to stimulation of the lateral part of the PBD (LPBD). In contrast, phenoxybenzamine, an alpha-adrenergic blocker, and atropine methylnitrate, a muscarinic blocker, had no effect. Because previous studies showed that bilateral lesions of the suprachiasmatic nucleus (SCN) eliminated hyperglycemia induced by intracranial injection of 2-deoxy-D-glucose and that blinding largely suppressed the hyperglycemia, the effects of these two treatments on hyperglycemia induced by electrical stimulation of the LPBD were examined. SCN lesions abolished the hyperglycemic response but did not affect the hyperglucagonemic response. Results 4 wk after orbital enucleation were similar to those after SCN lesions. These findings suggest that the SCN and a beta adrenergic mechanism are involved in the hyperglycemic response to LPBD stimulation. PMID- 2895587 TI - Somatostatin inhibition of secretagogue and forskolin-stimulated gastric acid secretion. AB - The action of somatostatin (SS) on acid secretion and histamine release was studied in isolated gastric mucosa of toads mounted in Ussing chambers. SS inhibited H+ secretion and histamine release stimulated by cholinergic and gastrinergic secretagogues. Exogenous histamine stimulation of H+ secretion was blocked noncompetitively by SS in a dose-dependent manner. In mucosae maximally stimulated by histamine or forskolin and cimetidine, acetylcholine (ACh) and tetragastrin (TG) induced a direct stimulation of the oxyntopeptic cell not inhibited by SS. Indomethacin, an inhibitor of prostaglandin synthesis, did not prevent SS inhibition of histamine stimulation. Pretreatment with SS abolished forskolin stimulation of H+ secretion. SS induced a small inhibition of the stimulatory effect of N6, 2'-O-dibutyryladenosine 3',5'-cyclic monophosphate. These results suggest that SS inhibits acid secretion stimulated by secretagogues through different mechanisms: 1) inhibition of histamine release by ACh and TG, 2) inhibition of endogenous and exogenous histamine stimulation through a blockade of adenylate cyclase, and 3) an inhibitory effect subsequent to the synthesis of adenosine 3',5'-cyclic monophosphate. The direct activation of the oxyntopeptic cell by ACh and TG does not seem to be affected by somatostatin. PMID- 2895586 TI - Peptide YY antagonizes beta-adrenergic-stimulated release of insulin in dogs. AB - Peptide YY (PYY) and neuropeptide Y (NPY) are peptides of 36 amino acids that share structural homologies with pancreatic polypeptide (PP). PP is predominantly found in the endocrine pancreas. PPY is primarily found in mucosal endocrine cells of the distal ileum, colon, and rectum, whereas NPY is found in both the peripheral and central nervous systems. Previous studies indicate that these peptides can interact with the autonomic nervous system. The objective of the present experiments was to study the effect of PYY on neurally stimulated insulin release [i.e., in response to 2-deoxy-D-glucose (2-DG), a nonmetabolizable glucose analogue] in conscious dogs. Intravenous administration of PYY (100, 200, and 400 pmol.kg-1.h-1) reduced 2-DG-stimulated insulin release in a dose dependent manner (P less than 0.05) without affecting plasma glucose levels. Administration of NPY (800 pmol.kg-1.h-1), but not PP (400 pmol.kg-1.h-1), reduced 2-DG-stimulated release of insulin (P less than 0.05). The inhibitory action of PYY on 2-DG-stimulated insulin release persisted in the presence of atropine or phentolamine treatment; however, hexamethonium alone or phentolamine plus propranolol treatment blocked the inhibitory action of PYY. Release of insulin stimulated by the beta-agonist isoproterenol was also inhibited by PYY (P less than 0.05). These results indicate that PYY can inhibit autonomic neurotransmission by a mechanism that may involve ganglionic or postganglionic inhibition of beta-adrenergic stimulation. Our findings suggest a role for PYY and NPY in the autonomic regulation of insulin release. PMID- 2895588 TI - Gastrin: levels and trophic action during advancing age. AB - Changes in antral and serum gastrin levels as well as gastrin (G) and somatostatin (D) cell density were examined in 4- to 16-mo-old Fischer-344 rats. In these rats, the responsiveness of the gastric mucosa to the trophic action of gastrin was also examined. It was observed that whereas serum gastrin levels declined steadily between 4 and 16 mo of age, antral gastrin levels rose sharply during this period. In the antrum of 16-mo-old rats, the density of G-cells, but not D-cells, was found to be lower than in their 4-mo-old counterparts. Thus, when D- to G-cell ratios were calculated, 16-mo-old rats revealed a 50% higher D- to G-cell ratio than the 4-mo-old animals. To assess the trophic action of gastrin, groups of 4-, 8-, and 16-mo-old rats were infused subcutaneously (osmotic minipump) with either saline or gastrin (G-17-I; 250 ng.kg-1.h-1) for 14 days. The gastric mucosa was assayed for thymidine kinase (an indicator of proliferative activity) and DNA and protein content. In the saline-infused rats, gastric mucosal thymidine kinase activity increased sharply between 4 and 16 mo of age without significantly affecting DNA or protein content (expressed as milligrams per 100 g of body weight), suggesting that the age-associated rise in proliferative activity is not accompanied by increased mucosal growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2895589 TI - Electrophysiological evidence for alpha 1- and alpha 2-adrenoceptors in solitary tract nucleus. AB - The effects of microiontophoresis of norepinephrine and epinephrine were examined on the spontaneous neuronal activity of single neurons in the nucleus tractus solitarius (NTS) in urethan-anesthetized rats. Neuronal responses to catecholamine iontophoresis were examined in the absence and presence of the alpha 1-adrenergic antagonist, prazosin, and the alpha 2-antagonist, idazoxan, to characterize the subtypes of alpha-adrenergic receptors mediating catecholamine action in this important autonomic nucleus. Norepinephrine produced inhibitions in firing, which were blocked primarily by idazoxan, whereas epinephrine-induced neuronal inhibitions were blocked by either prazosin or idazoxan. Inhibitions of spontaneous firing were also produced by iontophoresis of methoxamine, an alpha 1 selective agonist, or the alpha 2-selective agonist clonidine in all neurons that were tested. Neuronal responses to methoxamine were blocked selectively by prazosin, whereas the effects of clonidine were antagonized selectively by idazoxan. These data provide evidence at the level of the single unit that catecholamines may affect activity in the NTS via interactions with both alpha 1- and alpha 2-adrenergic receptors. PMID- 2895590 TI - Epidemiologic and clinical features of invasive amebiasis in Bangladesh: a case control comparison with other diarrheal diseases and postmortem findings. AB - To describe the epidemiologic and clinical features associated with invasive amebiasis in Bangladesh, 85 hospitalized diarrheal patients with hematophagous trophozoites of Entamoeba histolytica in their stools were compared to a control group of 84 hospitalized diarrheal patients without amebiasis. Postmortem examinations were carried out in 22 deaths due to amebiasis. For the patients with amebiasis, there was a bimodal age distribution with peaks at 2-3 years and greater than 40 years, whereas the control patients had a unimodal distribution with the peak at 0-1 year. The sex distribution was equal in childhood but young adults were predominantly female and older adults predominantly male. The clinical features significantly associated with amebiasis were prolonged dysentery, prior measles rash, malnutrition, hyponatremia, hypokalemia, and hypoproteinemia (all P less than 0.05). The case fatality rate in amebiasis was 29%, which was significantly higher than 11% for the controls (P less than 0.05). Postmortem findings included extensive colitis with deep ulcers and complications, including colonic perforation in 2 cases, peritonitis in 4 cases, pneumonia in 9 cases, and septicemia in 5 cases. These results indicate that invasive amebiasis in this population differs from other diarrheal diseases, affecting mainly children greater than 2 years and adults and causing severe and fatal illness characterized by extensive colitis with diverse systemic consequences. PMID- 2895591 TI - Vector potential of selected North American mosquito species for Rift Valley fever virus. AB - Selected North American mosquito species were evaluated as potential vectors of Rift Valley fever virus. Field populations of Aedes canadensis, Ae. cantator, Ae. excrucians, Ae. sollicitans, Ae. taeniorhynchus, Ae. triseriatus, Anopheles bradleyi-crucians, Culex salinarius, Cx. tarsalis, and Cx. territans perorally exposed to 10(6.2)-10(7.2) plaque forming units of Rift Valley fever virus readily became infected. Infection rates ranged from 51% (65/127) for Cx. salinarius to 96% (64/67) for Ae. canadensis. Disseminated infection rates were generally greater at 14 days than at 7 days after the infectious bloodmeal, and, with the exception of An. bradleyi-crucians, they were not significantly different than the pooled rate of 59% for each species tested. Only 5/55 (9%) of the An. bradleyi-crucians developed a disseminated infection. For most of the species, about half of the mosquitoes with a disseminated infection transmitted an infectious dose of virus to hamsters. While all species, with the exception of An. bradleyi-crucians, transmitted virus, Ae. canadensis, Ae. taeniorhynchus, and Cx. tarsalis had the highest vector potential of the species tested. Following inoculation of approximately 10(1.6) plaque forming units of virus, 100% of the mosquitoes of each species became infected. For most species, transmission rates were similar for inoculated individuals and those that developed a disseminated infection following peroral infection. Viral titers of transmitting and nontransmitting-disseminated individuals were similar for all species tested. These data suggest that, if Rift Valley fever virus was introduced into North America, several mosquito species would be capable of transmitting it. PMID- 2895592 TI - A comparison of midazolam and temazepam for premedication of day case patients. AB - One hundred patients who underwent day case surgery took part in a randomized double-blind comparison between midazolam 15 mg and temazepam 20 mg orally as premedicants. Postoperative recovery was studied using tests of psychomotor function. Midazolam produced a similar degree of anxiolysis to temazepam and a greater incidence of drowsiness. Recovery was similar after either premedicant and psychomotor function was still depressed 4 hours postoperatively (p less than 0.001). Nearly 90% of patients felt that they had benefitted from either premedicant. We conclude that midazolam is a suitable drug for premedication in day case surgery. PMID- 2895593 TI - Recurarisation after vecuronium? PMID- 2895594 TI - H2 antagonists and bupivacaine clearance. AB - The effect of the H2 receptor antagonists cimetidine and ranitidine on bupivacaine clearance was assessed in women scheduled to undergo elective Caesarean section under epidural anaesthesia. Thirty-six women were randomly allocated to receive either no medication, cimetidine 400 mg or ranitidine 150 mg on the night prior to and on the morning of surgery. No significant difference was found between the peak bupivacaine levels: the mean (SD) values were 0.74 (0.17) microgram/ml, 0.81 (0.38) microgram/ml and 0.70 (0.24) microgram/ml in the control, cimetidine and ranitidine groups, respectively. Similarly, the H2 receptor antagonists did not alter the plasma bupivacaine against time curves, half-life or bupivacaine clearance in the three groups studied. PMID- 2895595 TI - Sufentanil-midazolam anesthesia in malignant hyperthermia. PMID- 2895596 TI - Myocardial ischemia in untreated hypertensive patients: effect of a single small oral dose of a beta-adrenergic blocking agent. AB - In a non-double-blind, prospective, randomized study, the intra-operative electrocardiograms of 128 mildly hypertensive surgical patients were examined in order to determine the incidence of myocardial ischemia during anesthesia. No patient had been receiving chronic antihypertensive therapy prior to the study, but a single small oral dose of a beta-adrenergic blocking agent (labetalol, atenolol, or oxprenolol) was given to 89 of them along with premedication. Forty four per cent of the untreated control patients and 61% of the patients pretreated with a beta-adrenergic blocking agent had normal preoperative electrocardiograms and no risk factors for coronary artery disease other than hypertension (this difference between groups was not statistically significant). During tracheal intubation and/or emergence from anesthesia, a brief, self limited episode of myocardial ischemia was detected in 11 of 39 untreated control patients, and in two of 89 patients pretreated with a beta-adrenergic blocking agent (P less than 0.001). Tachycardia always accompanied the ischemic events, but a conspicuous increase in blood pressure did not. The authors conclude that mild hypertension, when untreated prior to the induction of anesthesia, is associated with a high incidence of myocardial ischemia; and that a single small oral dose of a beta-adrenergic blocking agent, given with pre-medication, can significantly reduce that risk. PMID- 2895597 TI - Inadvertent intra-arterial injection of vecuronium. PMID- 2895598 TI - An unusual presentation of periarteritis nodosa. AB - Periarteritis nodosa is characterized by generalized inflammation of medium and small arteries that leads to thrombosis or aneurysmal dilatation. We report the case of a 30-year-old man with no preceding signs or symptoms who presented initially with a chief complaint of mild abdominal pain. He deteriorated clinically during the next six to eight hours, and developed shock secondary to a ruptured aneurysm of the left gastric artery. His postoperative course was complicated by recurrent bleeding and death within 48 hours. Our case represents a protean clinical manifestation of periarteritis nodosa and expands the differential diagnosis of acute abdominal pain. PMID- 2895599 TI - Changing priorities in GI decontamination in toxic ingestions. PMID- 2895600 TI - Differential expression of the c-abl proto-oncogene and the homeo box-containing gene Hox 1.4 during mouse spermatogenesis. AB - Mammalian spermatogenesis is a complex developmental process. Spermatozoa, like ova, are uniquely capable of supporting embryonic development. Our approach to understanding this process is to identify genes whose developmental pattern of expression suggests that they may play a role in spermatogenesis. Experiments on the cellular oncogene c-abl and the homeo box-containing gene Hox-1.4 indicate that these genes may be important for male germ cell development. Both genes produce testis-specific transcripts that are present in particular cellular populations of the adult testis. Their developmental specificity, however, is different: c-abl is haploid-specific, whereas Hox-1.4 is expressed in the germ cells as soon as they have entered meiosis. Future studies will focus on examining the protein products of these genes and their function in testicular cells. PMID- 2895601 TI - Free composite serratus anterior muscle--rib flap for reconstruction of severely damaged foot. AB - A 23-year-old man who underwent below-knee amputation of one leg and sustained extensive soft-tissue damage with a bony defect of the other foot presented an unusual reconstructive problem. By means of microsurgical techniques a free serratus anterior-rib flap was transferred to restore function of the foot. A four-year follow-up showed good rehabilitation. PMID- 2895602 TI - Studies into the immunopathogenesis and laboratory diagnosis of dengue haemorrhagic fever. AB - Studies were carried out into the immunopathogenesis and laboratory diagnosis of dengue virus infections. Using an experimental system it was shown that cell mediated immunity (CMI), as measured by delayed-type hypersensitivity (DTH) was induced in mice infected with dengue virus. The nature of the DTH response satisfies most criteria for a classical DTH reaction. In addition, it was also shown that infection with dengue virus causes a transient immunosuppression as measured by the immune response to other, unrelated antigens. With regard to the laboratory diagnosis of dengue infections, it was found that mosquito cells were a sensitive system for the isolation of dengue viruses and that the success of isolation was related to the antibody content of the serum. A new method for the rapid isolation of dengue viruses was also developed involving the intracerebral inoculation of mosquito larvae. By the use of this method viral antigens can be detected as early as 2-3 days after specimen inoculation. The significance of these findings in relation to the immunopathogenesis, prevention and control of disease syndromes due to dengue viruses is discussed. PMID- 2895603 TI - Haemorrhagic fever with renal syndrome: clinical, virological and epidemiological perspectives. AB - Haemorrhagic fever with renal syndrome (HFRS) is caused by a group of RNA viruses within the family of Bunyaviridae known as hantaviruses. The classical, severe form of HFRS is characterized by fever, headache, abdominal and lumbar pain, proteinuria, haemorrhagic phenomena, shock and renal failure. The disease is associated with the prototype Hantaan virus and occurs in rural areas of Korea and China with Apodemus mice as reservoir hosts. A clinically less severe form of HFRS, which is caused by Seoul virus, occurs in urban areas with the house rat Rattus novegicus as the main reservoir host. The disease in nonendemic areas may be atypical and patients with symptoms the hepatitis and minimal renal involvement have been observed in Malaysia. Outbreaks of HFRS in humans involving infected laboratory rat colonies have occurred in several medical centres in various countries. Hantaviruses cause a chronic, asymptomatic infection in rodents which excrete the virus in their lungs, saliva and urine. Man becomes infected mainly by inhalation of infected droplets from healthy rodent carriers. Seroepidemiological studies using mainly the indirect immunoflourescent antibody test of sera from humans and rats showed that hantaviruses have a worldwide distribution. PMID- 2895604 TI - Treatment of undescended testes with hMG and hMG plus hCG: clinical, hormonal and sonographic evaluation. AB - 20 children (mean age 4, 6 yrs), of whom 13 had unilateral and 7 had bilateral cryptorchidism were treated with hMG: 40 I.U. three i.m. injections per week for six or eight weeks. Where there was no descent of testis, treatment was continued with hMG at the same dosage plus hCG 500 I.U. one i.m. injection per week for an additional four weeks. The children were tested for FSH, LH and Testosterone serum levels at the beginning of treatment and after 6, 8 and 14 weeks. We obtained testicular descent in 10 out of 20 cases treated. Ultrasonography enabled us to locate the undescended testes in all cases and to follow the response to treatment. PMID- 2895605 TI - Intraspecies genotypic heterogeneity among Mycoplasma gallisepticum strains. AB - The DNA cleavage patterns and protein profiles of six Mycoplasma gallisepticum strains from various parts of the world were compared. Obvious differences among the strains were obtained by DNA restriction analysis. Reflection of genotypic variations in the polypeptide patterns was less pronounced; slight differences in the protein profiles of the strains were found. The data presented here indicate that some intraspecies polymorphism exists among M. gallisepticum strains. PMID- 2895606 TI - The effect of sodium butyrate on tyrosine aminotransferase induction in primary cultures of normal adult rat hepatocytes. AB - Treatment of primary cultures of adult rat hepatocytes with 5 mM butyrate inhibited the spontaneous decrease in basal activity and mRNA levels of tyrosine aminotransferase (TAT) that occurred during culture (Staecker et al., submitted). We report here that butyrate treatment of primary cultures of rat hepatocytes initially inhibited the induction of TAT. This inhibition was followed by a period of accelerated TAT induction. TAT induction in butyrate-treated primary cultures of adult rat hepatocytes occurred only after metabolism of butyrate by the cultured hepatocytes. The accelerated induction of TAT in hepatocyte cultures treated with sodium butyrate was reflected by increased TAT activity and mRNA levels. Cultured hepatocytes rapidly metabolized butyrate, but the addition of more butyrate into cultures after its initial metabolism resulted in a rapid reduction in TAT activity. These findings indicate that butyrate treatment can affect the expression of TAT in primary hepatocyte cultures in both a positive (increased basal TAT expression) and a negative (inhibition of the induced expression of TAT) manner. PMID- 2895607 TI - Functional dissection of nuclear envelope mRNA translocation system: effects of phorbol ester and a monoclonal antibody recognizing cytoskeletal structures. AB - Unidirectional transport of poly(A)-containing mRNA [poly(A)+ mRNA] through the nuclear envelope pore complex is thought to be an energy (ATP or GTP)-dependent process which involves a nuclear envelope nucleoside triphosphatase (NTPase). In the intact envelope, this enzyme is regulatable by poly(A) binding and by poly(A) dependent phosphorylation/dephosphorylation of other components of the mRNA translocation system, which are as yet unidentified. Monoclonal antibodies (mAbs) were elicited against the poly(A) binding nuclear envelope fraction isolated from rat liver. The mAbs were screened for their modulatory effects on mRNA transport in vitro. One stable clone decreased the efflux of rapidly labeled RNA and of one specific mRNA (ovalbumin) from isolated nuclei. It increased the binding of poly(A) to the envelope and increased the maximal catalytic rate of the NTPase, but it did not alter the apparent Km of the enzyme or the extent of its stimulation by poly(A). The nuclear envelope-associated protein kinase that down regulates the NTPase was inhibited by the antibody, while other protein kinases were not affected. Because both the NTPase and mRNA efflux were inhibited by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate, the sensitive kinase is probably protein kinase C. Protein kinase C was found to be associated with the isolated nuclear envelope. The antibody reacted with both a Mr 83,000 and a Mr 65,000 nuclear envelope polypeptide from rat liver and other tissues. By immunofluorescence microscopy in CV-1 cells, the antibody localized to the nuclear envelope and, in addition, to cytoplasmic filaments which show some superposition with the microfilament network. PMID- 2895608 TI - Characterization of the fibrin polymer structure that accelerates thrombin cleavage of plasma factor XIII. AB - The effect of plasmin-derived fibrin(ogen) degradation products on alpha-thrombin cleavage of plasma Factor XIII was studied to identify the fibrin polymer structure that promotes Factor XIIIa formation. Fibrin polymers derived from fibrinogen and Fragment X enhanced the rate of thrombin cleavage of plasma Factor XIII in plasma or buffered solutions. The concentrations of fibrinogen and Fragment X that promoted half-maximal rates of Factor XIIIa formation were 5 and 40 micrograms/ml, respectively. Fragments Y, D, E, D-dimer, and photooxidized fibrinogen did not enhance thrombin cleavage of Factor XIII. Although purified Fragment D1 inhibited fibrin gelation, the soluble protofibrils promoted thrombin activation of Factor XIII. Noncrosslinked fibrin fibers failed to enhance thrombin cleavage of Factor XIII. In conclusion, soluble fibrin oligomers function to promote thrombin cleavage of plasma Factor XIII during blood clotting. PMID- 2895609 TI - Acid phosphomonoesterase heterogeneity in axenically grown Entamoeba histolytica. PMID- 2895610 TI - An EEG and behavioural study on the excitatory properties of caffeine in rabbits. AB - In the present work we have investigated some of the excitatory effects of caffeine in rabbits. Caffeine (5-50 mg/kg i.v.) elicited a cortical EEG desynchronization and an activation of the theta hippocampal rhythm but failed to affect the red nucleus activity. The EEG effects of caffeine were counteracted by L-PIA (1-3 mg/kg i.v.). Caffeine (25-50 mg/kg i.v.) completely reverted the EEG and motor effects due to L-PIA (1-5 mg/kg); the drug also counteracted the cortical and hippocampal EEG modifications elicited by diazepam (1-10 mg/kg), but failed to influence the diazepam-induced effects at the red nucleus level. In addition, caffeine (25 mg/kg) significantly increased the duration of the epileptiform EEG response (afterdischarge) elicited by electrical stimulation of the dorsal hippocampus. This caffeine-potentiating effect was reduced by administration of both L-PIA (0.05-2 mg/kg) and diazepam (1 mg/kg); Ro 15-1788 (1 mg/kg) was unable to affect it. Present data suggest that the analeptic action of caffeine is different from that of the drugs acting through the GABA benzodiazepine system. Our results show the importance of the limbic system in the excitatory effects of caffeine and suggest that purinergic drugs may have a modulatory role in the control of limbic convulsions. PMID- 2895611 TI - Systemic haemodynamic and beta-adrenoceptor antagonistic effects of bisoprolol in conscious pigs: a comparison with propranolol. AB - We studied the cardiovascular profile of the new cardioselective beta adrenoceptor antagonist bisoprolol in the conscious pig and compared this profile with that of propranolol. Acute i.v. administration of bisoprolol (16-1024 micrograms.kg-1) did not affect mean arterial blood pressure but caused dose related decreases in cardiac output (from 8 to 17%; p less than 0.05) due to a negative chronotropic action (heart rate reduction ranging from 9 to 21%; p less than 0.05) as stroke volume was unaffected. Max LVdP/dt decreased (ranging from 18 to 27%; p less than 0.05) while left ventricular end-diastolic blood pressure (from 8.6 +/- 0.6 to 15 +/- 0.2 mmHg; p less than 0.05) and systemic vascular resistance (from 8 to 18%; p less than 0.05) increased. Propranolol in a dose range from 25-300 micrograms.kg-1 produced strikingly similar changes. Bisoprolol was more effective in antagonizing the isoproterenol-induced responses of max LVdP/dt than those on either heart rate or diastolic arterial blood pressure, whereas propranolol caused equi-effective inhibitions of the responses of heart rate and max LVdP/dt. However, with propranolol also the inhibition of the diastolic arterial blood pressure was less marked than for the other parameters. Propranolol proved to be the more potent beta-adrenoceptor antagonist, as the isoproterenol dose ratios of all 3 parameters during beta-adrenoceptors blockade with propranolol exceeded those obtained with bisoprolol. PMID- 2895612 TI - Increased alpha 1- and decreased alpha 2-adrenoceptor sensitivities upon chronic treatment with imipramine in mediating cardiovascular responses in pithed rats. AB - After chronic treatment with imipramine (20 mg/kg, i.p., twice daily for 14 days) the pressor dose-response curves to phenylephrine, methoxamine and cirazoline (alpha 1-adrenoceptor agonists) significantly shifted to the left with decreased PD50 values in pithed rats; however, the dose-response curve to Sgd 101/75, a selective alpha 1-adrenoceptor agonist was not affected. On the other hand, the alpha 2-adrenoceptor agonists such as B-HT 920, xylazine and clonidine produced a rightward shift for both the pressor (increased PD50) and cardioinhibition (increased ID50) dose-response curves in these rats. These results required treatment with imipramine over 2 weeks. Chronic treatment with imipramine has reduced the antagonism by prazosin of the pressor effect of phenylephrine when compared with the dose-ratios between the 2 groups. On the contrary, the antagonism by piperoxan of the cardioinhibitory effect of B-HT 920 was rather enhanced by the treatment, but that of the pressor effect of B-HT 920 was little changed. In cerebrocortical membrane fractions obtained from rats pretreated with imipramine, Ki of phenylephrine to displace [3H]prazosin was decreased, whereas that of clonidine and yohimbine to displace [3H]yohimbine was increased. In conclusion, it is demonstrated that after chronic imipramine treatment the peripheral alpha 2-adrenoceptors (both presynaptic and postsynaptic sites) as well as central alpha 2-adrenoceptors respond with a decreased sensitivity to the alpha 2-adrenoceptor agonists, and moreover, this treatment produces an increased sensitivity of the central and peripheral alpha 1-adrenoceptors to the alpha 1 adrenoceptor full agonists. PMID- 2895613 TI - Alpha-adrenoceptor-blocking properties of some trypanocidal diamidines. AB - A series of trypanocidal diamidines and diimidazolines known to cause severe hypotension were tested for their alpha-adrenoceptor blocking properties in vitro. At the postsynaptic alpha 1-receptor of the guinea-pig aorta in vitro all compounds at doses of 0.5 to 50 mumol/l showed weak antagonistic effects against noradrenaline. Similar results were obtained at the presynaptic alpha 2-receptor of the rat vas deferens. PMID- 2895614 TI - Structure-activity relationship of organic nitrates for activation of guanylate cyclase. AB - The effect of different organic nitrates on the activity of soluble guanylate cyclase prepared from rat liver was investigated. We found a close correlation between the number of nitrate ester groups and the potency of guanylate cyclase activation. For erythrityl tetranitrate (ETN, EC50 = 14.5 microM), glyceryl trinitrate (GTN, EC50 = 60 microM), isoidide dinitrate (IIDN, EC50 = 0.24 mM) and isosorbide-5-nitrate (IS-5-N, EC50 = 1 mM), we were able to set up an equation by which the EC50 could be calculated from the number of nitrate groups per molecule. Compared to these results, the effect of sterical factors and lipophilicity on organic nitrate-induced activation of guanylate cyclase was small. However, there were still significant differences in the EC50 values for the cyclic mononitrates. Isosorbide-2-nitrate (IS-2-N, EC50 = 0.75 mM) was found to be more potent than the stereoisomeric isosorbide-5-nitrate. Similarly, the cyclic dinitrates isomannide dinitrate (IMDN, EC50 = 0.20 mM), isoidide dinitrate and isosorbide dinitrate (ISDN, EC50 = 0.28 mM) exhibited small but significant differences in their guanylate cyclase stimulatory potency. Two lipophilic ester derivatives of isosorbide-5-nitrate showed a 2-fold potency difference for vasodilation but were equipotent for activation of guanylate cyclase (EC50 = 0.85 mM). Also, the increase in lipophilicity due to esterification of the free hydroxylic group had no major influence on guanylate cyclase activation by isosorbide-5-nitrate. These results demonstrate that in a cell-free system, the potency of organic nitrates for guanylate cyclase activation is mainly determined by the number of nitrate groups. Since organic nitrate-induced activation of guanylate cyclase may involve the formation of nitric oxide free radicals, it is conceivable that the differences in potency reflect a varying degree of nitric oxide release from each compound tested. PMID- 2895615 TI - Effects of antihistamines on the spinal reflex in rats. AB - The effect of antihistamines on the spinal reflex in rats was studied. When H1 blocking agents such as pyrilamine, promethazine and diphenhydramine were given intravenously, both monosynaptic reflex (MSR) and polysynaptic reflex potentials (PSR) were inhibited in a dose-dependent fashion without affecting the dorsal root reflex and dorsal root-dorsal root potential. The extent of suppression of the MSR and PSR measured in spinal rats was smaller than that of intact rats. When H1-blocking agents (0.25-5.0 nmol) were applied by intraspinal microinjection close to the motoneuron, the MSR and PSR were depressed dose dependently. Simultaneous application of carbachol partially blocked the inhibitory effects of H1-blocking agents induced by intraspinal microinjection. Also, the motoneuron discharges evoked by microinjection of glutamic acid or acetylcholine were depressed by simultaneous administration of any of H1-blocking agents tested. However, H2-blocking agents, such as cimetidine and ranitidine, given either intravenously or intraspinally had a scarcely measurable effect on the spinal reflex. The depression of H1-blocking agents on the spinal reflex is due to a direct inhibition of the motoneuron on the one hand. On the other hand, there is also an involvement of higher centers in the central nervous system increasing potential depression. PMID- 2895616 TI - Beta-blockers and mental performance. PMID- 2895618 TI - Central nervous system side effects with beta-blockers. PMID- 2895617 TI - Clinical evaluation of calcium metabolism in adult T-cell leukemia/lymphoma. AB - To clarify the mechanism of development of hypercalcemia in adult T-cell leukemia/lymphoma (ATLL), ten patients with a serum creatinine level less than 177 mumol/L (2 mg/dL) were examined. Although hypercalcemia was seen in only four (40%) of these patients, four of six normocalcemic patients showed hypercalciuria (greater than 5 mmol/d [greater than 200 mg/24 h]). All hypercalcemic patients exhibited high nephrogenous cyclic adenosine monophosphate (NcAMP) levels in the face of low-normal immunoreactive parathyroid hormone and reduced serum 1,25 dihydroxyvitamin D [1,25(OH)2D] concentration. Half of the hypercalciuric patients with normocalcemia also showed high NcAMP and reduced serum 1,25(OH)2D levels. Furthermore, the changes in NcAMP and serum 1,25(OH)2D concentration closely paralleled the development of hypercalcemia and hypercalciuria in two patients. These results are reminiscent of the syndrome of humoral hypercalcemia of malignancy and suggest that derangements in calcium metabolism develop by a similar mechanism in patients with ATLL. The present data also indicate the importance of the measurement of urinary calcium excretion for early detection and prevention of fatal hypercalcemia in patients with ATLL. PMID- 2895620 TI - [Evaluation of anti-ischemia treatment in man]. PMID- 2895619 TI - [The value of NMR spectroscopy in the study of myocardial ischemia and in cardiovascular pharmacology]. AB - Nuclear magnetic resonance spectroscopy is a non-destructive method used to investigate the intracellular repercussions of experimental myocardial ischaemia. The effectiveness of drugs or cardioplegic agents in preserving myocardial metabolism during and immediately after ischaemia can be tested on various models. The results obtained in different experiments and the metabolic studies conducted in patients treated with cardiotropic drugs illustrate the value of this method in cardiovascular pharmacology. PMID- 2895621 TI - [Somatostatin in a case of neonatal hyperinsulinism caused by focal adenomatosis of the head of pancreas]. AB - The use of somatostatin in the treatment of a newborn infant with hyperinsulinism is reported. When administered alone, somatostatin was only able to prevent hypoglycemia for a short period of time, whereas the addition of a constant infusion of glucagon allowed successful control of the patient's hypoglycemia. As hyperinsulinism relapsed after a subtotal pancreatectomy, a trial was carried out with a somatostatin analog, which has an expected longer duration of action. It led to a significant rise in the blood glucose level but failed to prevent safely hypoglycemia even when 4 injections were performed daily. PMID- 2895622 TI - Drug therapy for agoraphobia. PMID- 2895623 TI - The cause and treatment of agoraphobia. PMID- 2895624 TI - Cell surface hydrophobicity of Klebsiella strains. AB - On 14 encapsulated Klebsiella strains with different K-antigens and their non encapsulated mutants the type of fimbriae present and the grade of hydrophobicity of their cell surface (expressed as SAT-value) were investigated. It could be demonstrated that clear correlations exist between the fimbriation of Klebsiella bacteria and their cell surface hydrophobicity. On the other hand, the presence of capsules and the type of K-antigen showed no influence on the degree of hydrophobicity. PMID- 2895625 TI - The College of American Pathologists Conferences. PMID- 2895626 TI - College of American Pathologists Conference XIII on the evaluation of proficiency testing results for quantitative methods in relation to clinical usefulness: review and comments. PMID- 2895627 TI - Inhibition of metabolic cooperation in vitro and enhancement of enzyme altered foci incidence in rat liver by the pyrethroid insecticide fenvalerate. AB - The synthetic pyrethroids cypermethrin, delta-methrin, fenvalerate, permethrin, and the fenvalerate metabolite p-chlorophenylisovaleric acid were investigated for inhibition of gap-junctional intercellular communication in vitro in the Chinese hamster lung fibroblast (V79) metabolic cooperation assay. Fenvalerate was furthermore studied for enhancement of gamma-glutamyl transpeptidase-positive enzyme altered foci incidence in partially hepatectomized, nitrosodiethylamine initiated male Sprague Dawley rats. The in vitro studies showed that fenvalerate and p-chlorophenylisovaleric acid were inhibitors of intercellular communication at non-cytotoxic concentrations while cypermethrin, deltamethrin, and permethrin were inactive. In the in vivo study in rat liver, fenvalerate administered p.o. (75 mg/kg/day) 5 days a week for 10 weeks induced significantly more foci per cm3 and a larger percentage of liver tissue occupied by foci tissue compared to a vehicle control group. Analysis of size distributions of foci in fenvalerate- and vehicle-treated rats showed elevated foci incidences in fenvalerate-treated rats at all foci sizes. Fenvalerate induced no hepatotoxic effects as judged by plasma transaminase activities and histopathology. The results of this study suggest fenvalerate to be a potential tumour promoter. PMID- 2895628 TI - Complications of plasma exchange in the treatment of polyarteritis nodosa and Churg-Strauss angiitis and the contribution of adjuvant immunosuppressive therapy: a randomized trial in 72 patients. AB - We recorded side effects and other complications of 813 plasma exchanges used in early treatment of polyarteritis nodosa and Churg-Strauss angiitis in a prospective study of 72 patients (22-75 years old). All the patients were also treated with a corticosteroid (1 mg/kg/day), and half were included in a randomized trial of cyclophosphamide (2 mg/kg/day during 1 year). Centrifugation was used in 678 plasma exchange sessions (83.4%) and filtration in 128 (15.7%) (no data were available about the technique used in seven cases). The replacement fluid in 745 sessions was 4% albumin and in 115 was fresh-frozen plasma; eight patients received both (47 sessions). Two hundred and fifty-one complications were reported in 60 patients during 206 (25.3%) of the 813 completed exchanges; 47 sessions (5.8%) were temporarily stopped as a result of complications. The most common problems were technical difficulties (in 90 sessions), moderate or severe hypotension (in 52), and allergy to the replacement fluid (in 51). Hepatitis B antigen appeared in one patient. In four patients, plasma exchange was stopped permanently because of the severe side effects. No patient died during a session. Twelve of the 72 patients died during the study, six in each of the two groups. In the group treated by a combination of corticosteroid and plasma exchange, deaths were related to the deleterious effects of the disease itself and occurred after 12.8 +/- 11.1 months (1-26 months). In the group treated by the same combination plus cyclophosphamide, four of the six deaths were due to severe infections, which were related to leukopenia in three patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2895629 TI - The sequential demonstration of non-specific esterase reactivity Ia antigen and Thy-1 antigen in murine epidermal sheets. AB - Immunofluorescence demonstrating Ia and Thy-1 antigens and non-specific esterase (NSE) enzyme histochemistry were performed sequentially on sheets of ear epidermis from CBA, C3H.OH, A/J, and Balb/c mice. The same areas of epidermis were photographed after each reaction and individual cells identified and compared. Thy-1+ dendritic cells expressed neither Ia antigen nor NSE reactivity. No cell was found to express Ia antigen or NSE alone: thus all Langerhans cells (LC) in normal murine epidermis appeared to co-express Ia antigen and NSE reactivity. LC expressing greatly increased amounts of Ia antigen were occasionally seen apposed to Thy-1+ cells suggesting that these cells may be immunologically active--perhaps involved in antigen presentation. PMID- 2895630 TI - Multicenter trial of cryotherapy for retinopathy of prematurity. Preliminary results. Cryotherapy for Retinopathy of Prematurity Cooperative Group. AB - We report the preliminary three-month outcome of a multicenter randomized trial of cryotherapy for treatment of retinopathy of prematurity (ROP). Transscleral cryotherapy to the avascular retina was applied in one randomly selected eye when there was threshold disease (defined as five or more contiguous or eight cumulative 30 degrees sectors [clock hours] of stage 3 ROP in zone 1 or 2 in the presence of "plus" disease). An unfavorable outcome was defined as posterior retinal detachment, retinal fold involving the macula, or retrolental tissue. At this writing, 172 infants had been examined three months after randomization. An unfavorable outcome was significantly less frequent in the eyes undergoing cryotherapy (21.8%) compared with the untreated eyes (43%). While the surgery was stressful, no unexpected complications occurred during or following treatment. These data support the efficacy of cryotherapy in reducing by approximately one half the risk of unfavorable retinal outcome from threshold ROP. PMID- 2895631 TI - The trouble with doctors. PMID- 2895632 TI - Primary structure of rat liver alkaline phosphatase deduced from its cDNA. AB - Rat liver alkaline phosphatase (ALP) was markedly induced by treatment of rats by bile-duct ligation and colchicine injection. Taking this advantage for enrichment of ALP mRNA, we constructed a lambda gt11 liver cDNA library using polyadenylated RNA prepared from the treated rat liver, and isolated an ALP cDNA clone. The 2165 bp cDNA contained an open reading frame that encodes a 524-amino-acid-residue polypeptide with a predicted molecular mass of 57737 Da. The precursor protein contained a presumed signal peptide of 17 amino acid residues followed by 28 amino acid residues identical with the N-terminal sequence determined from the purified rat liver ALP. It was also confirmed that amino acid sequences of two CNBr-cleavage peptides obtained from liver ALP were contained within the cDNA encoded protein. Five possible N-linked glycosylation sites were found in the molecule and a highly hydrophobic amino acid sequence at the C-terminus. The deduced polypeptide of rat liver ALP showed 88% homology to that of the human liver-type enzyme in osteosarcoma cells. RNA blot hybridization analysis identified a single species of ALP mRNA with 2.7 kb in both the control and the treated rat livers. An approx. 20-fold increase of the mRNA was detected in the treated liver at 12 h after the onset of stimulation, compared with that in the control liver. PMID- 2895633 TI - Glutamine metabolism in isolated incubated adipocytes of the rat. AB - 1. Phosphate-dependent glutaminase activity in the epididymal fat-pad was 15.1 nmol/min per mg of protein. Glutaminase activity demonstrated differences with respect to adipose-tissue sites. Considerable variation was found in different sites of adipose tissue from lean control and Zucker obese animals. 2. Adipocytes incubated in the presence of 2 mM-glutamine utilized glutamine at a rate of 1.8 mumol/h per g dry wt., and glutamate, ammonia, lactate and alanine were produced. Addition of glucose plus insulin increased the rates of glutamine utilization and glutamate, ammonia, lactate and alanine production. Isoprenaline alone or plus glucose further stimulated the rate of glutamine utilization and formation of end products. 3. The rate of incorporation of 14C from glutamine into CO2 was similar to that of glucose, but the rate of incorporation into triacylglycerol was much less. Addition of unlabelled glucose or glucose plus insulin stimulated the rate of incorporation of [14C]glutamine into triacylglycerol, but had no effect on that of 14CO2 formation. Isoprenaline plus glucose increased the rate of incorporation of [14C]glutamine into CO2, but decreased the rate of incorporation into triacylglycerol. 4. In the absence of insulin, the rate of [14C]glutamine incorporation into triacylglycerol was related to the glucose concentration (0-10 mM). However, in the presence of insulin, the rate of incorporation of [14C]glutamine was maximal at 1 mM-glucose. PMID- 2895634 TI - Phosphorylation of C-protein, troponin I and phospholamban in isolated rabbit hearts. AB - Phosphorylation of myofibrillar and sacroplasmic-reticulum (SR) proteins was studied in Langendorff-perfused rabbit hearts subjected to various inotropic interventions. Stimulation of hearts with isoprenaline resulted in the phosphorylation of both troponin I (TnI) and C-protein in myofibrils and phospholamban in SR. Phosphorylation of phospholamban could be reversed by a 15 min perfusion with drug-free buffer, after a 1 minute pulse perfusion with isoprenaline, at which time the mechanical effects of isoprenaline stimulation had also been reversed. However, both TnI and C-protein remained phosphorylated at this time. Moreover, the inhibition of Ca2+ activation of the Mg2+-dependent ATPase (Mg-ATPase) activity associated with myofibrillar phosphorylation persisted in myofibrils prepared from hearts frozen after 15 min of washout of isoprenaline. To assess the contribution of C-protein phosphorylation in the decrease of Ca2+ activation of the myofibrillar Mg-ATPase activity, we reconstituted a regulated actomyosin system in which only C-protein was phosphorylated. In this system, C-protein phosphorylation did not contribute to the decrease in Ca2+ activation of Mg-ATPase activity, indicating that TnI phosphorylation is responsible for the diminished sensitivity of the myofibrils to Ca2+. These observations support the hypothesis that phospholamban phosphorylation plays a more dominant role than TnI or C-protein phosphorylation in the mechanical response of the mammalian heart to beta-adrenergic stimulation. PMID- 2895635 TI - Acute effects of a beta-adrenoceptor agonist (BRL 26830A) on rat brown-adipose tissue mitochondria. Increased GDP binding and GDP-sensitive proton conductance without changes in the concentration of uncoupling protein. AB - GDP binding, proton conductance and the specific concentration of uncoupling protein were measured in brown-adipose-tissue mitochondria of rats treated acutely with the novel beta-agonist, BRL 26830A. At 1 h after dosing with BRL 26830A, mitochondrial GDP binding was increased more than 2-fold. The increase in binding resulted from an increase in the number of binding sites. An iterative analysis of Scatchard binding data suggested that there is only one high-affinity GDP-binding site (Kd 0.3 microM) in brown-adipose-tissue mitochondria. The acute increase in GDP binding produced by treatment with BRL 26830A occurred without any alteration in the specific mitochondrial concentration of uncoupling protein, as determined by radioimmunoassay. Treatment with the beta-agonist did, however, lead to a small increase in the GDP-sensitive component of mitochondrial proton conductance. These results indicate that GDP-binding sites on uncoupling protein can be rapidly unmasked after treatment with a brown-fat-specific beta-agonist, and that the increase in binding reflects an increase in the activity of the mitochondrial proton-conductance pathway. PMID- 2895636 TI - An 'in situ' perfusion system suitable for investigating mammary-tissue metabolism in the lactating rat. Hormonal regulation of acetyl-CoA carboxylase. AB - A technique is described for the non-recirculating perfusion of inguinal/abdominal mammary tissue in situ in anaesthetized lactating rats. Tissue viability was maintained, without resort to infusion of vasoactive chemicals which may also be effectors of cellular metabolism, for at least 90 min. Total tissue adenine nucleotides (per mg of DNA) were somewhat decreased in perfused relative to non-perfused mammary tissue. DNA content (per g wet wt. of tissue) was diminished after 90 min of perfusion to approx. 65% of its value in control tissue. Adenylate energy-charge ratios were lower in perfused tissue in the absence of hormones than in control tissue. They were increased to control values by the presence of either insulin or isoprenaline in the perfusate. No changes occurred in flow rate of the perfusate that might account for these increases. In mammary tissue perfused without addition of hormones, acetyl-CoA carboxylase activities were similar to those measured in control tissue samples, although activity-ratio measurements implied some increase in the phosphorylation of this enzyme. Insulin or isoprenaline increased the activity of acetyl-CoA carboxylase, especially when this was measured at low concentrations of citrate. Confirming conclusions from previous experiments with mammary acini and explant preparations, insulin activated acetyl-CoA carboxylase in mammary tissue, but inhibition of its activity was not mediated by cyclic AMP. PMID- 2895637 TI - Alpha 1- and beta-adrenergic receptors in brown adipose tissue of lean (Fa/?) and obese (fa/fa) Zucker rats. Effects of cold-acclimation, sucrose feeding and adrenalectomy. AB - 1. The populations of alpha 1- and beta-adrenergic receptors in brown adipose tissue (BAT) of genetically obese Zucker rats (fa/fa) were studied with [3H]prazosin and [3H]CGP-12177 respectively. 2. The density of alpha 1-adrenergic receptors in BAT was significantly lower in obese than in lean Zucker rats, both at 2-4 months of age and at 6 weeks of age. The density of beta-adrenergic receptors was identical in BAT of lean and obese 6-week-old Zucker rats. 3. Cold acclimation increased the alpha 1-receptor density significantly in BAT of both lean and obese Zucker rats, and the number of beta-receptors was also somewhat increased. 4. Sucrose feeding did not affect the density of alpha 1-receptors in BAT of lean or obese Zucker rats, but it increased beta-receptor density. 5. Adrenalectomy restored the density of alpha 1-adrenergic receptors in BAT of obese Zucker rats to the value observed in lean rats. 6. It is concluded that there is a direct correlation between alpha 1-receptor density and tissue recruitment, and that alpha 1-receptor density is thus positively correlated with sympathetic activity. beta-Receptor density is apparently better correlated with feeding conditions. PMID- 2895639 TI - Subcellular localization of transglutaminase. Effect of collagen. AB - 1. The subcellular distribution of transglutaminase was investigated by using the analytical approach of differential and isopycnic centrifugation as applied to three organs of the rat: liver, kidney and lung. After differential centrifugation by the method of de Duve, Pressman, Gianetto, Wattiaux & Appelmans [(1955) Biochem. J. 63, 604-617], transglutaminase is mostly recovered in the unsedimentable fraction S and the nuclear fraction N. After isopycnic centrifugation of the N fraction in a sucrose density gradient, a high proportion of the enzyme remains at the top of the gradient; a second but minor peak of activity is present in high-density regions, where a small proportion of 5' nucleotidase, a plasma-membrane marker, is present together with a large proportion of collagen recovered in that fraction. 2. Fractions where a peak of transglutaminase was apparent in the sucrose gradient were examined by electron microscopy. The main components are large membrane sheets with extracellular matrix and free collagen fibers. 3. As these results seem to indicate that some correlation exists between particulate transglutaminase distribution and those of collagen and plasma membranes, the possible binding of transglutaminase by collagen (type I) and by purified rat liver plasma membrane was investigated. 4. The binding studies indicated that collagen is able to bind transglutaminase and to make complexes with plasma-membrane fragments whose density is higher than that of plasma-membrane fragments alone. Transglutaminase cannot be removed from such complexes by 1% Triton X-100, but can be to a relatively large extent by 0.5 M-KCl and by 50% (w/v) glycerol. 5. Such results suggest that the apparent association of transglutaminase with plasma membrane originates from binding in vitro of the cytosolic enzyme to plasma membrane bound to collagen, which takes place during homogenization of the tissue, when the soluble enzyme and extracellular components are brought together. PMID- 2895640 TI - Stepwise degradation of the hexapeptide Met-Ala-Ser-Pro-Phe-Ala by dipeptidyl peptidase IV. AB - Dipeptidyl peptidase IV (dipeptidyl-peptide hydrolase, EC 3.4.14.-) purified from pig kidney was proved to split off the N-terminal dipeptide Met1-Ala2 and, subsequently the dipeptide Ser3-Pro4 from the synthetic model peptide Met-Ala-Ser Pro-Phe-Ala representing the N-terminal part of a signal sequence of leucocyte interferon. The kinetic parameters for the release of Met1-Ala2 (Km 3.2.10(-5) mol.l-1 and Ser3-Pro4 (Km 1.65.10(-4) mol.l-1, kcat57.9 s-1) were determined. The dipeptides Ser-Pro and Phe-Ala were found to be competitive inhibitors of the hydrolysis of Gly-Pro-NHNp by dipeptidyl peptidase IV. PMID- 2895638 TI - The beta 2-adrenergic receptors of human epidermoid carcinoma cells bear two different types of oligosaccharides which influence expression on the cell surface. AB - The beta 2-adrenergic receptors of the human epidermoid carcinoma A431 cells reside on two polypeptide chains revealed by photoaffinity labelling with [125I]iodocyanopindolol-diazirine. These proteins correspond to two distinct populations of N-asparagine-linked glycoproteins: the 55-52 kDa molecules are associated with complex carbohydrate chain(s), the 65-63 kDa component with polymannosidic carbohydrate chain(s). Both types of receptors are present in preconfluent cells, but only the polymannosidic type is found in the postconfluent cells. Moreover, complex chains appear to be associated with the receptors with the highest affinity for (-)-isoproterenol and polymannosidic chains with the receptors with the lowest affinity for this agonist. the carbohydrate moiety of the beta-adrenergic receptor is involved in the expression and function of the beta 2-adrenergic receptors at the surface of the A431 cells, since tunicamycin and monensin, complete and partial inhibitors of glycosylation respectively, diminish the number of binding sites at the cell surface and increase the total number of sites in the cell. In these conditions a diminution of cyclic AMP accumulation is also observed. PMID- 2895641 TI - [alpha-Aminomethylketones as inhibitors of a membrane-bound alanine aminopeptidase]. AB - Methyl ketone derivatives of L-amino acids are substrate analogous inhibitors of membrane bound alanine aminopeptidase (EC 3.4.11.2) from Acinetobacter calcoaceticus. The type of inhibition is competitive. Compounds with a branched aliphatic side chain are most effective so that valine methyl ketone was found to be the best inhibitor of the enzyme with a K-value of 5.5.10(-7) mol.l-1. PMID- 2895642 TI - The influence of long-term treatment with haloperidol on neuronal activity and sensitivity in several brain structures of the rat. AB - The influence of long-term haloperidol pretreatment on neuronal spontaneous activity and transmitter sensitivity was investigated in prefrontal cortex, hippocampus and locus coeruleus. The changes are different in all areas as well as in the transmission systems involved. In particular cases, analogies exist between haloperidol- and isolation-induced changes, reflecting a comparable dopaminergic supersensitivity. PMID- 2895643 TI - The potency of fluorinated ether anesthetics correlates with their 19F spin-spin relaxation times in brain tissue. AB - In this study, four fluorinated ether anesthetics and one non-anesthetic fluorinated alkane were observed in rat brain and adipose tissue using 19F-NMR spectroscopy. Measurements of 19F spin-spin relaxation times (T2) of the anesthetics in brain revealed T2 values (0.5-4.5 msec) that correlated linearly with the anesthetic potency (ED50) of the drugs. The non-anesthetic was present at very low concentrations in brain and had a T2 value (18.5 msec) far longer than that of any of the anesthetics. All of the drugs were present at high concentration in peripheral adipose tissue. 19F T2 values for these drugs in adipose tissue (200-400 msec) were far larger than the values observed in brain and did not correlate with anesthetic potency. These results indicate that volatile anesthetic molecules have a specific affinity for neural tissue and that immobilization of anesthetic molecules in brain correlates with anesthetic potency. The results with adipose tissue suggest that the interaction of anesthetic with brain tissue cannot be explained by a simple partition of these drugs into lipid. PMID- 2895644 TI - Dibutyryl cAMP induction of type II 5'deiodinase activity in rat brain astrocytes in culture. AB - Dibutyryl cAMP treatment of cultured rat astrocytes results in the rapid appearance of T4 to T3 conversion catalyzed by type II iodothyronine 5'deiodinase, without altering other deiodinating pathways. Induction of enzyme activity was time-dependent with a lag period of 60 min, reaching plateau levels after 6-8 hours, and required continued synthesis of mRNA and new protein. Isoproterenol also induced T4 to T3 converting activity through beta-adrenergic receptor mediated interactions. These data suggest that dibutyryl cAMP stimulated astrocytes provide an excellent model for the study of the molecular and cellular events modulating T4 to T3 conversion in the brain. PMID- 2895646 TI - Dynorphin A (1-13) peptide NH groups are solvent exposed: FT-IR and 500 MHz 1H NMR spectroscopic evidence. AB - FT-IR spectroscopic studies of dynorphin A(1-13) in H2O and D2O are utilized to derive the aqueous phase secondary structure of the opioid peptide. Resolution enhancement of the amide I region of dynorphin A(1-13) in H2O revealed a doublet at 1652 cm-1 and 1669 cm-1 which are interpreted as indicative of "unordered" and extended structures. From FT-IR and 1H NMR deuterium exchange studies, the peptide NH groups appeared to be solvent accessible which is suggestive of an essentially extended structure with aperiodically interwoven "unordered" structure. The results are consistent with Raman Spectroscopic (Rapaka et al., (1987) Int. J. Peptide Protein Res. 30:284-287) and 2D NMR studies (Huang et al. submitted), from our laboratory. PMID- 2895645 TI - The rapid desensitization of receptors for platelet derived growth factor, bradykinin and ATP: studies on individual cells using quantitative digital video fluorescence microscopy. AB - The rise in free cytosolic Ca2+ of individual response to growth factors was studied in serum starved cultures of 3T3 fibroblasts. Quantitative digital video fluorescence microscopy revealed that with platelet derived growth factor (PDGF) there was a lag period between stimulation and Ca2+ response, with considerable cell-to-cell variation, whereas ATP, bradykinin and fetal calf serum induced an immediate, synchronous response. A coverslip with attached cells was mounted on a small flow chamber, allowing complete change of medium in 2 sec. Using this technique, homologous desensitization to a second addition of agonist 2 min after removal of the first addition was found for all agonists. Unusual heterologous desensitization was observed in that PDGF desensitized the cells to the other agonists, yet the reverse did not occur. PMID- 2895647 TI - cDNA cloning of esterase 1, the major esterase activity in mouse plasma. AB - We report here the cloning of a partial cDNA for Esterase 1, the major esterase activity in mouse plasma. A 470 base pair insert was isolated from a lambda gt11 cDNA library constructed from mouse liver poly A+ RNA, and identified by hybrid selected translation. We show that the sexual dimorphism displayed in the plasma levels of this protein is caused by a difference at the level of transcription. In addition, RFLP data using mouse recombinant inbred strains mapped this clone at the Es-1 locus on mouse chromosome 8. PMID- 2895649 TI - Cloned hst gene from normal human leukocyte DNA transforms NIH3T3 cells. AB - The hst gene was originally identified as a transforming gene in DNAs from stomach cancers and a noncancerous portion of stomach mucosa by transfection assays using NIH3T3 cells (1,2). Subsequently, the hst gene obtained directly from leukocyte DNA of a leukemia patient was sequenced (3,4). Here, cosmid clones containing the hst gene were isolated directly from normal human leukocyte DNA and from T361-2nd-1 cells, a secondary transformant of NIH3T3 cells induced by transfection of DNA from a stomach cancer. All clones containing the hst gene from these different sources transformed NIH3T3 cells with similar efficiency. Restriction map of the hst gene from normal leukocyte DNA was identical with that from leukocyte DNA of a leukemia patient, while the hst gene from T361-2nd-1 cells was rearranged at the 168th nucleotide upstream of the TATA box. PMID- 2895648 TI - Characterization of the catalytic domain of bovine adrenal tyrosine hydroxylase. AB - Mild trypsin proteolysis of tyrosine hydroxylase (TH) produces a 34 kDa fragment which is catalytically active. To determine the structure of the trypsin-digested tyrosine hydroxylase (tTH) relative to the native enzyme and to regulatory phosphorylation sites, bovine adrenal tTH was purified to homogeneity and the sequence of 17 amino acids from the N-terminus was determined. These data indicate that the N-terminus of tTH corresponds to amino acid 158. Thus the catalytic region is contained within the central region of enzyme approximately 17 kDa from the N-terminal and 5 kDa from the C-terminal and does not include phosphorylation sites located in the N-terminus. This region of TH shares a high degree of homology with phenylalanine hydroxylase and tryptophan hydroxylase and thus reflects a selective conservation of regions required for catalysis in contrast to the non-homologous regulatory sites. Activation by proteolysis corresponds to an increase in affinity for both substrate and cofactor indicating that the region removed by proteolysis imposes additional constraints on substrate and cofactor binding. These data are consistent with the model that the catalytic core of TH is contained within a 34 kDa region in the highly conserved central portion of the molecule whereas the non-homologous N-terminus regulates cofactor binding and directs substrate specificity. PMID- 2895650 TI - Hypolipidemic drug clofibrate induces hepatic dedifferentiation. AB - The effect of clofibrate on rat liver enzymes and metabolites was compared with that produced by partial hepatectomy and an extrahepatic tumor. Clofibrate administration produced decrease in gamma-glutamyltranspeptidase (GGT) activity with concomitant increase in glutathione concentration. The drug was able to exert its GGT-lowering effect even when fed to tumor-bearing animals. Presence of an extrahepatic neoplasm as well as administration of clofibrate resulted in marked decrease in activities of hepatic arginase and ornithine transaminase. Administration of clofibrate to the tumor-bearing rat produced a further decrease in activities of these two enzymes. These results suggest that clofibrate causes hepatic dedifferentiation and simulates an extrahepatic tumor. However, clofibrate did not induce any significant increase in polyamine profile unlike the other two experimental conditions. PMID- 2895651 TI - Regulation of endometrial transglutaminase activity during the menstrual cycle. AB - When human endometrial transglutaminase was measured a 10-fold higher activity was detected during the secretive phase. This change was not related to either differences in solubility of the enzyme or to selective contamination by plasma factor XIII and rather appears to depend on the expression of the tissue form of transglutaminase, suggesting that this enzyme is regulated in vivo by progesterone. PMID- 2895652 TI - In vitro selectivity of agonists and antagonists for beta 1- and beta 2 adrenoceptor subtypes in rat brain. AB - A radioreceptor binding assay was developed to determine the selectivity of beta adrenoceptor agents in rat brain. This was achieved by using the highly selective unlabelled antagonists CGP 20712A and ICI 118-551 to block beta 1- or beta 2-sub populations respectively in rat cerebral cortex membranes. This permitted the selective labelling of beta-adrenoceptors with the antagonist (-)-[125I]pindolol. Using this method, compounds could be routinely screened and selectivity profiles for binding in the CNS determined with a high degree of sensitivity and resolution. PMID- 2895653 TI - Effects of phenylarsine oxide on agonist-induced hepatic vasoconstriction and glycogenolysis. PMID- 2895654 TI - Genetic influences on agonist binding to cardiac beta-receptors. AB - Regulation of beta-adrenoceptor-agonist function in the Maudsley Reactive (MR/Har) and the Maudsley Non-Reactive (MNRA/Har) rat strains was assessed by comparison of isoproterenol competition for [125I]iodocyanopindolol (ICYP) binding sites in crude left ventricular homogenate preparations. Non-linear, least-squares analysis of isoproterenol competition for ICYP binding in the absence of guanine nucleotide revealed different proportions of high- and low affinity receptors in the two strains; MR/Har rats (59 +/- 3.3%) had a significantly greater proportion of receptors in the high-affinity state than the MNRA/Har rats (41 +/- 4.5%). Addition of the non-hydrolyzable guanine nucleotide analog guanylylimidodiphosphate (Gpp(NH)p) converted receptors to the low affinity state. Analysis of Gpp(NH)p concentration-response curves in left ventricular homogenates of the two strains revealed that the MR/Har strain had a significantly (P less than 0.02) lower EC50 for guanyl nucleotide inhibition of isoproterenol competition for ICYP binding than the MNRA/Har. Confirming previous experimental results, a significantly (P less than 0.04) greater density of ventricular beta-receptors was found in MR/Har rats (13.16 +/- 0.92 fmol/mg protein) than in MNRA/Har rats (10.81 +/- 0.63 fmol/mg protein). Left ventricular catecholamine levels were found to be correlated inversely with beta-adrenoceptor density in the two strains; norepinephrine (NE) and epinephrine (EPI) concentrations (ng/mg protein) in left ventricle were 12.19 +/- 0.94 for NE and 0.165 +/- 0.038 for EPI in MNRA/Har, and 8.73 +/- 0.95 and 0.018 +/- 0.018, respectively, in MR/Har. All other parameters of agonist interactions with the cardiac beta-adrenoceptor for the MR/Har and MNRA/Har rat strains were similar [the IC50 for displacement of ICYP binding by isoproterenol, the accompanying Hill coefficients in the Gpp(NH)p present and absent condition, the Kd of the high- and low-affinity states in the absence of Gpp(NH)p, and the Kd of the uniform low-affinity state in the presence of Gpp(NH)p]. We hypothesize that the strain-dependent differences in high-affinity state formation reported here may account for some of the in vivo differences in cardiovascular function previously demonstrated in the Maudsley rats. PMID- 2895655 TI - Effect of dopamine on tyrosine hydroxylase in cultured rat adrenal medulla. AB - Explants of rat adrenal medulla were cultured in defined medium for up to 22 hr. Addition of dopamine to the medium led to a diminution in the activity of tyrosine hydroxylase (tyrosine 3-monooxygenase; EC 1.14.16.2) in the tissue. The enzyme activity was inversely proportional to the concentration of dopamine in the culture medium. The extent of loss of tyrosine hydroxylase, as measured by immunochemical titration, corresponded to the degree of loss in enzyme activity under the same conditions. The decreased amount of enzyme protein was due to a decrease in the rate of synthesis of tyrosine hydroxylase. However, this effect was not specific in that the relative rate of tyrosine hydroxylase synthesis was not decreased. Metabolites of dopamine when added to the medium did not affect tyrosine hydroxylase activity. Two other adrenal medullary enzymes, monoamine oxidase (EC 1.4.3.4) and acid phosphatase (EC 3.1.3.2), were not affected by addition of dopamine to the medium. The results indicate that elevated cytoplasmic levels of dopamine decrease the concentration of tyrosine hydroxylase by inhibiting protein synthesis. PMID- 2895656 TI - Azidopine photoaffinity labeling of multidrug resistance-associated glycoproteins. PMID- 2895657 TI - Characterization of genetic markers in the 3' end of the apo B gene and their use in family and population studies. AB - The 3' end of the apo B gene is highly polymorphic. Two point mutations in the coding sequence of the gene create EcoRI (E+, E-) and XbaI (X+, X-) RFLPs. The two loci are in random association and the frequency of the four haplotypes, E+X+, E+X-, E-X+ and E-X- in the normolipidaemic population are 0.68, 0.30, 0.02 and 0.00, respectively. Although the polymorphic nucleotide underlying the EcoRI RFLP creates an amino acid substitution in the apo B protein (Glu----Lys) in a region close to a putative LDL-receptor recognition site(s), we find no statistically significant difference in the frequency of the apo BGlu and apo BLys alleles in hyperlipidaemic patients (familial hypercholesterolaemia, type IIA with no tendon xanthomas, IIB and probably IV) and the normolipidaemic population. In contrast, we confirm previous findings, that the X+ allele is in linkage disequilibrium with a genetic locus that predisposes to the development of higher fasting plasma triglyceride levels than the X- allele. We have characterized a highly polymorphic region immediately 3' to the apo B gene. At least 5 alleles of this locus exist in the population and our family studies show it should be an extremely informative locus to use in studies where polymorphic or mutant apo B alleles are suspected to underly certain forms of familial hyperlipidaemia. DNA sequence analysis of this highly polymorphic locus shows that the variation is entirely attributable to the number of times the simple repeating sequence 5'-TTTATAATTAAAATATTTATAATTAAATAT-3' is present. PMID- 2895658 TI - DNA polymorphisms of the gene for apolipoprotein B in patients with peripheral arterial disease. AB - We have determined the frequency of DNA polymorphisms of the gene for human apolipoprotein B, detected with XbaI and EcoRI, in 205 patients with documented peripheral arterial disease. Of the patients, 78 have no evidence of disease in the coronary and carotid arteries, 64 have coexisting coronary artery disease but no evidence of carotid artery disease, 26 patients have coexisting carotid artery disease but no evidence of coronary artery disease, and 37 have coexisting coronary and carotid artery disease. Levels of triglycerides, cholesterol and apolipoprotein B were measured for each patient, and RFLP frequency was determined in all the patients. Lipid, lipoprotein and apolipoprotein levels were not significantly different between the different patient groups. Compared with a sample from the clinically well London population, the frequency of the R2 allele of the polymorphism detected with EcoRI, and the frequency of the X1 allele of the XbaI polymorphism was significantly higher in the patient group. The frequency of these alleles was not significantly different in the different patient groups. In patients with only peripheral arterial disease, individuals with the XbaI genotype X1X1 have the lowest and those with the genotype X2X2 have the highest mean levels of serum cholesterol. However, in all other patient groups this trend was reversed (X1X1 highest and X2X2 lowest). Our observations suggest that variation at the apo B locus is one of the factors involved in predisposing an individual to develop arterial disease but does not determine where in the arterial system the disease develops. PMID- 2895659 TI - Variations in the apolipoprotein AI-CIII-AIV gene region and in lecithin:cholesterol acyltransferase concentration are determinants of plasma cholesterol concentrations. AB - We have examined the effects of variation in the region of the apolipoprotein (apo) AI-CII-AIV genes, and in plasma lecithin: cholesterol acyltransferase (LCAT) concentration, on plasma cholesterol concentration in 109 unrelated men aged 52-67 yrs. Restriction fragment length polymorphisms (RFLPs) were detected using the restriction enzymes XmnI, PstI and SstI and individuals were divided into groups using information from all three RFLPs in conjunction. Mean plasma concentrations of both total cholesterol and estimated low density lipoprotein cholesterol differed significantly (P less than 0.0125) among groups of men with different genotypes. Thus, variation in this gene region may be one of the polygenetic factors involved in determining cholesterol levels in the normal population. In the same subjects, plasma cholesterol was also positively correlated with plasma LCAT concentration (r = 0.55, P less than 0.001), due mainly to an increase in the cholesteryl ester content of apo B-containing lipoproteins with increasing LCAT concentration. Since apolipoproteins AI, CIII and AIV have each been shown to modify the activity of LCAT in vitro, the associations of the RFLPs with plasma cholesterol concentration may reflect changes in LCAT activity secondary to qualitative or quantitative changes in one or more of these apolipoproteins. PMID- 2895660 TI - The decrease of low serum gamma glutamyl transferase during short-term abstinence. AB - We present a study of 107 in-patients of a detoxification center. As expected, 81 percent of them showed upon admittance an increased serum gamma glutamyl transferase (GGT). After alcohol withdrawal, GGT decreased in all but one of these patients. More surprisingly, even among the rest of the patients exhibiting upon admittance a GGT result within the reference range, there still occurred a significant decrease in 50 percent of the cases. Thus, whether the initial GGT is high or normal, we observed a decrease in 96 patients out of 107, i.e., a sensitivity of 0.90. The decrease test consists in asking a subject to refrain from any alcohol intake during a short period, e.g., seven days. If any significant diminution of serum GGT occurs, the possibility of alcohol abuse should at least be given serious consideration before being rejected. This test was used up to now only when GGT was initially high. The present results show that it can be attempted even when GGT is initially within the normal range, with a sensitivity of 0.90. PMID- 2895661 TI - A new electrophoretic variant of arylsulfatase A. AB - Previous work in this laboratory has identified electrophoretic variant forms of arylsulfatase A in leucocyte plus platelets. During a study to replicate and extend these findings, a new seven-band variant of arylsulfatase A has been identified. Purified platelets gave a clearer, more distinct electrophoretic banding pattern than the leucocyte and platelet preparations. PMID- 2895662 TI - Coronary heart disease in the Medical Research Council trial of treatment of mild hypertension. Medical Research Council Working Party on Mild Hypertension. AB - Seventeen thousand three hundred and fifty four mildly hypertensive people with diastolic blood pressures between 90 and 109 mm Hg at screening were randomised to active treatment, with bendrofluazide or propranolol, or to placebo tablets. They were followed for a maximum of five and a half years, giving a total of 85,572 patient-years of observation. There were 456 myocardial infarctions or sudden coronary deaths. Drug treatment did not affect the overall rate of coronary events. Rates per thousand person-years were 8.3 and 9.0 in men and 1.8 and 1.7 in women in the active treatment and placebo groups respectively. Event rates were much higher in smokers than in non-smokers on placebo treatment (12.6 and 7.5 in men and 3.5 and 1.0 in women in smokers and non-smokers respectively). An analysis of subgroup results showed a lower event rate in non-smoking men on propranolol than in non-smokers on placebo (5.0 and 7.5 per thousand person-years respectively). Bendrofluazide had no apparent effect on the event rate. The interaction between the type of treatment (propranolol, bendrofluazide, or placebo) and smoking in determining the coronary event rate was not statistically significant, however. The incidence of electrocardiographic changes of silent infarction--that is major Q/QS abnormalities--differed little with sex, smoking habit, or treatment with either active drug. PMID- 2895663 TI - Intraocular pressure changes during rapid sequence induction of anaesthesia: comparison of propofol and thiopentone in combination with vecuronium. AB - Intraocular pressure (IOP) was measured during rapid sequence induction of anaesthesia using thiopentone or propofol as the induction agent and vecuronium for neuromuscular blockade. Vecuronium was administered in a dose of 0.15 mg kg-1 approximately 35 s before the induction agent. IOP was measured with a handheld applanation tonometer before anaesthesia, following administration of the induction agent, immediately after tracheal intubation and cuff inflation and 1, 2 and 3 min later. IOP in the propofol group was significantly lower than in the thiopentone group, except immediately after induction, when reduction in IOP was similar and significant with both agents. IOP following intubation in patients in whom anaesthesia was induced with thiopentone was not significantly different from baseline values, but showed a significant increase from the pressure before intubation. In contrast, IOP after intubation in the propofol group remained not only significantly less than the baseline value, but also showed only a minimal and insignificant change in comparison with values before intubation. The frequency of side effects was low in both groups except for a significantly greater reduction in arterial pressure in those receiving propofol. PMID- 2895664 TI - Controlled comparison of a new sublingual lormetazepam formulation and i.v. diazepam in outpatient minor oral surgery. AB - In a randomized, double-blind, parallel groups study, 40 patients undergoing surgical removal of impacted 3rd molar teeth received either sublingual lormetazepam 2.5 mg (n = 20) in a new cellulose wafer formulation followed at 35 min by i.v. saline; or sublingual placebo followed at 35 min by i.v. diazepam 10 mg (Diazemuls). Rapid onset of sedation was seen after sublingual lormetazepam, while the course and duration of postoperative sedation, measured using standard psychometric tests, was similar following both treatments. Surgeons' ratings indicated that sublingual lormetazepam was comparable to i.v. diazepam but patients' ratings indicated greater satisfaction with and preference for i.v. diazepam. Significant anterograde amnesia was found following both treatments. Both treatments were tolerated well, with no significant cardiovascular complications. These results indicate that sublingual lormetazepam may have a role in anaesthesia as a premedicant and for conscious sedation. PMID- 2895665 TI - Use of vecuronium and doxapram in patients susceptible to malignant hyperthermia. AB - Neuromuscular blockade was obtained with vecuronium 108 micrograms kg-1 in 44 patients undergoing diagnostic muscle biopsy as part of an investigation of malignant hyperthermia (MH) susceptibility. At the termination of anaesthesia doxapram 1.43 mg kg-1 was given in an attempt to antagonize postoperative respiratory depression. Rectal, muscle and skin temperatures, blood lactate concentration and venous PCO2 were measured before, during and after anaesthesia. Susceptibility to MH was established by in vitro contracture tests according to the protocol of the European MH Group. Twenty patients were susceptible to MH (MHS), 19 were MH non-susceptible (MHN) and five MH equivocal (MHE). No adverse effects of the drugs were observed. There were no differences between the three groups in rectal or muscle temperature, blood lactate concentration or venous PCO2 at any time. Doxapram did not prevent an increase in postoperative PCO2. It is concluded that vecuronium and doxapram may be safely administered to patients susceptible to MH. PMID- 2895666 TI - Terfenadine: an anti-allergic drug. PMID- 2895668 TI - Oxidative phosphorylation in a hybrid system containing bovine heart membranes and pea mitochondrial F1-ATPase. AB - Purified pea mitochondrial F1-ATPase reconstituted oxidative phosphorylation in both partially and completely F1-depleted bovine heart mitochondrial membranes. The isolated plant enzyme exhibited high rates of ATP synthesis when combined with bovine heart membranes, suggesting great evolutionary conservation of the ATP synthase complex in mitochondria. PMID- 2895667 TI - The proton pore in the Escherichia coli F0F1-ATPase: substitution of glutamate by glutamine at position 219 of the alpha-subunit prevents F0-mediated proton permeability. AB - Three mutations in the uncB gene encoding the a-subunit of the F0 portion of the F0F1-ATPase of Escherichia coli were produced by site-directed mutagenesis. These mutations directed the substitution of Glu-219 by Gln, or of Lys-203 by Ile, or of Glu-196 by Ala. Strains carrying either the Lys-203 or Glu-196 substitutions showed growth characteristics indistinguishable from the coupled control strain. Properties of membrane preparations from these strains were also similar to those from the coupled control strain. The substitution of Glu-219 by Gln resulted in a strain which was unable to utilise succinate as sole carbon source and had a growth-yield characteristic of an uncoupled strain. Membrane preparations of the Glu-219 mutant were proton impermeable and the F1-ATPase activity was inhibited by about 50% when membrane-bound. The results are discussed with reference to a previously proposed intramembranous proton pore involving subunits a and c. PMID- 2895670 TI - Immobilization of acetylcoenzyme A synthetase and the preparation of an enzyme reactor for the synthesis of [11C]acetylcoenzyme A. AB - The enzyme acetylcoenzyme A synthetase (acetate-CoA ligase (AMP forming), EC 6.2.1.1) from Saccharomyces cerevisiae (baker's yeast) is used for the synthesis of 1 mumol [11C]acetylcoenzyme A. (CoA-[11C]Ac). A screening of the immobilization of the enzyme on differently derivatized controlled pore glass beads (50 nm pore size and 125-180 micron particle size) was performed. Several silanes, spacer arms and terminal reactive groups were tested. The immobilized enzyme was subjected to storage stability tests. From these experiments, the method of choice was selected: immobilization on CNBr-activated controlled pore glass. The immobilized parameters were optimized further to improve the activity of the enzyme-loaded glass beads. The latter were packed in a glass column. The kinetic properties of the column were investigated and optimized to obtain an almost complete conversion of 1 mumol acetate into acetylcoenzyme A (CoA-Ac) within a few minutes. This is realized with an enzyme reactor (13.0 x 0.5 cm) containing 6.12 U active acetylcoenzyme A synthetase immobilized onto 1 g controlled pore glass. PMID- 2895669 TI - Effect of perfringolysin O on the lateral diffusion constant of membrane proteins of hepatocytes as revealed by fluorescence recovery after photobleaching. AB - Perfringolysin O is a thiol-activated cytolytic exotoxin the primary receptor of which is the membrane cholesterol on the cell surface. The effect of perfringolysin O was tested in various hepatocyte preparations. (i) Smears of fresh liver exposed to a mild H2O2 (1.0 mM) injury for 10 min at 37 degrees C, develop a 'peroxide-induced autofluorescence' (PIAF) on the membrane proteins. PIAF is suitable for measuring the average lateral diffusion constant (D) of the membrane proteins by means of fluorescence recovery after photobleaching technique (FRAP). Incubation for 5 min with 600 or 2000 units/ml of the perfringolysin O resulted in a significant increase (32 and 46%, respectively) of D as compared to the controls of the same age group (13-14 months). Various tests like heat denaturation of cholesterol saturation of perfringolysin O before its application as well as thiol-activation of the smears with dithiothreitol revealed that the increase of D is a specific toxin effect due mot probably to the reaction of perfringolysin O with cholesterol. (ii) Isolated hepatocytes were exposed to perfringolysin O and their viability as well as the release of two cytosolic enzymes (lactate dehydrogenase and glutamic-pyruvic transaminase) were measured; 40-60 units/ml of perfringolysin O in 30 min reduced the viability of the hepatocytes to zero and caused a release of about 70% of both cytosolic enzymes. The significance of the results is discussed from the points of view of both the toxin-effect and the FRAP method. PMID- 2895671 TI - 31P-NMR saturation transfer studies of aerobic Escherichia coli cells. AB - 31P-NMR measurements of saturation transfer have been used to measure the flux between Pi and ATP in Escherichia coli cells respiring on an endogenous carbon source. Measurements were made in the wild type and in cells genetically modified to give a 5-fold higher concentration of the F1F0-ATP synthase. The flux in the two cell types was not significantly different. This, together with studies using inhibitors specific for the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase and the ATP synthase, suggests that the observed flux arises predominantly from glycolytic rather than ATP synthase activity. Although this conclusion is in disagreement with previous experiments on E. coli, it is in agreement with recent experiments on yeast. PMID- 2895672 TI - Clinical value of thyrotropin binding inhibiting immunoglobulins (TBII) assay in hyperthyroidism. AB - More than 500 sera were assayed for TBII under routine conditions using "Trak" assay in order to evaluate the sensitivity, specificity and prognostic interest of this determination in hyperthyroidism. The sensitivity for the diagnosis of Graves' disease was 83.5%, better in ophthalmopathic patients (93%) than in non ophthalmopathic patients (75%). The specificity was 99.4% with only one false positive in a hypothyroid patient. TBII level significantly decreases with carbimazole treatment except in patients who remain hyperthyroid. Determination of TBII before stopping carbimazole treatment or after surgery has a prognostic significance as a positive value indicates a relapse in almost all cases. Conversely, a fall of TBII to normal levels with treatment is insufficient to assess recovery. High levels are frequently observed after radioiodine therapy but do not indicate a poor prognosis. PMID- 2895673 TI - Carbon recycling in materially closed ecological life support systems. AB - Materially closed microbial ecosystems represent model life support systems for the future human habitation of space. These ecosystems when subjected to a constant energy flux seem to be reliable and self-sufficient systems for recycling of biologically produced carbon compounds. PMID- 2895674 TI - Defective T cell-mediated, isotype-specific immunoglobulin regulation in B cell chronic lymphocytic leukemia. AB - The consistent occurrence of T cell abnormalities in patients with B cell chronic lymphocytic leukemia (B-CLL) suggest that the non-neoplastic host T cells may be involved in the pathogenesis of this B cell neoplasm. Because potential defects of immunoglobulin regulation are evident in B-CLL patients, we investigated one aspect of this by studying the T cell-mediated immunoglobulin isotype-specific immunoregulatory circuit in B-CLL. The existence of class-specific immunoglobulin regulatory mechanisms mediated by Fc receptor-bearing T cells (FcR + T) through soluble immunoglobulin binding factors (IgBFs) has been well established in many experimental systems. IgBFs can both suppress and enhance B cell activity in an isotype-specific manner. We investigated the apparently abnormal IgA regulation in a B-CLL patient (CLL249) whose B cells secrete primarily IgA in vitro. Enumeration of FcR + T cells showed a disproportionate increase in IgA FcR + T cells in the peripheral blood of this patient. Our studies showed that the neoplastic B cells were not intrinsically unresponsive to the suppressing component of IgABF produced from normal T cells, but rather the IgABF produced by the CLL249 host T cells was defective. CLL249 IgABF was unable to suppress IgA secretion by host or normal B cells and enhanced the in vitro proliferation of the host B cells. Size fractionation of both normal and CLL249 IgABF by gel filtration high-performance liquid chromatography (HPLC) demonstrated differences in the ultraviolet-absorbing components of IgABF obtained from normal T cells v that from our patient with defective IgA regulation. Such T cell dysfunction may not be restricted to IgA regulation, since we have found similar expansion of isotype-specific FcR + T cells associated with expansion of the corresponding B cell clone in other patients with B-CLL. These data suggest that this T cell mediated regulatory circuit could be significantly involved in the pathogenesis of B-CLL. PMID- 2895676 TI - HTLV-I-induced lymphoma mimicking Hodgkin's disease. Diagnosis by polymerase chain reaction amplification of specific HTLV-I sequences in tumor DNA. AB - A patient with a localized HTLV-I-associated lymphoproliferative disease that was misdiagnosed as Hodgkin's disease is presented. The patient's serum was negative for HTLV-I antibodies by enzyme-linked immunosorbent assay (ELISA), Western blot, and radioimmunoprecipitation. Tumor tissue DNA was negative for HTLV-I by Southern blotting but was positive for distinct HTLV-I sequences when subjected to DNA amplification using the polymerase chain reaction. We conclude that the clinical and pathologic diagnosis of HTLV-I-related lymphoma can be difficult and can be confused with Hodgkin's disease. Extremely sensitive molecular biological techniques may be required to establish a diagnosis of HTLV-I-induced lymphoma. PMID- 2895675 TI - Soluble interleukin 2 receptors in sera of Japanese patients with adult T cell leukemia mark activity of disease. AB - Serum concentrations of soluble interleukin 2 receptors (sIL 2R) were measured by an enzyme-linked immunosorbent assay (ELISA) in 30 patients with adult T cell leukemia (ATL), in 9 patients with other hematopoietic malignancies, and in 17 asymptomatic individuals seropositive for human T cell leukemia virus type I (HTLV-I). Sixty HTLV-I seronegative, age-matched controls showed a normal range of form 63.2 to 480.8 U/mL. All asymptomatic carriers of HTLV-I had sIL 2R in their sera within the normal range. sIL 2R in sera was not related to the anti HTLV-I antibody titer. Eleven patients with acute ATL, a clinical phenotype with median survival rate of 4.4 months, had markedly elevated sIL 2R (11,100 to 99,000 U/mL), but eight patients with smoldering ATL had low sIL 2R values (less than 480.8 U/mL) comparable to controls. Eleven patients with chronic ATL had intermediate elevated levels of sIL 2R (480.8 to 37,300.0 U/mL). Serum levels of sIL 2R correlated with the number of ATL cells (r = 0.812) and CD25-positive cells (r = 0.725) circulating in the peripheral blood. Longitudinal studies performed in four patients with ATL showed significant correlation between serum concentration of sIL 2R and activity of the malignancy. These findings suggest that the level of sIL 2R in serum indicated tumor load and, possibly, prognosis. PMID- 2895677 TI - Spectrin Oran (alpha II/21), a new spectrin variant concerning the alpha II domain and causing severe elliptocytosis in the homozygous state. AB - We report on spectrin Oran (alpha II/21), a new spectrin variant found in an Algerian family. It was characterized by the absence of the spots that classically correspond to the alpha II domain using two-dimensional analysis of spectrin limit digests. On the contrary, the abnormal domain was represented by a new set of spots in the 21-Kd and 16-Kd regions, as demonstrated by Western blots using anti-alpha II domain polyclonal antibodies. Spectrin Oran (alpha II/21) was found in the homozygous state in two children belonging to two separate branches of the family. It yields a severe elliptocytosis. Spectrin self-association was altered. The variant was much more difficult to prove in the heterozygous state, in which it results in no clinical and virtually no morphological symptom. In all four parents involved, however, electrophoretic analysis and Western blots showed the existence of the alpha II 21-Kd and 16-Kd peptides. In one parent, who combines spectrin Oran (alpha II/21) and the alpha II type-2 polymorphism, the two-dimensional spots (52, 39, 34, and 29 Kd) were quantified and appeared reduced by 30%: there was an intermediary decrease of spectrin self-association in this person. In the three other parents, spectrin Oran combined with the alpha II type-1 polymorphism. The alpha II type-1 spots (46, 35, 30, and 25 Kd) appeared in normal range, and spectrin self-association was normal. Along with previous observations, the present data emphasize the large fluctuations of the alpha-variant percentage. Provided spectrin Oran was present in a sufficient proportion, we found an associated alteration of the beta II domain (that faces the alpha II domain in the spectrin dimer): the beta II 65-Kd fragment was reduced and the beta II 52-Kd fragment was reciprocally increased. PMID- 2895678 TI - A possible variant of the neuroleptic malignant syndrome. AB - A 20-year-old man developed generalised rigidity and signs of autonomic instability following the introduction of therapy with zuclopenthixol decanoate. A diagnosis of NMS was made, despite the absence of hyperthermia. He recovered on treatment with thiamine, dantrolene, and bromocriptine. PMID- 2895679 TI - MAOIs and narcotic analgesics. PMID- 2895681 TI - Polyclonal lymphocytosis of T-cells associated with human T-cell leukemia virus I. AB - A patient with antibodies to human T-cell leukemia virus type I and the presence of integrated sequences of this virus in T-lymphocytes was investigated. In contrast to previous reports, the T-cell lymphocytosis was found to be polyclonal by analysis of human T-cell leukemia virus type I integration sites and T-cell antigen receptor rearrangements. Polyclonal T-cell infection by human T-cell leukemia virus type I may represent an infrequently observed stage of leukemogenesis. PMID- 2895680 TI - Nonrandom expression of polypeptide hormones in pancreatic endocrine tumors. An immunohistochemical study in a case of multiple islet cell neoplasia. AB - One hundred four endocrine tumors found in the body and tail of the pancreas of a patient with the Zollinger-Ellison syndrome (ZES) and multiple endocrine neoplasia (MEN-I) were investigated by immunohistochemistry for insulin, glucagon, somatostatin, pancreatic polypeptide (PP), and gastrin. The results for each tumor were scored into six grades according to the frequency of immunoreactive cells. Pancreatic polypeptide, glucagon, insulin, and somatostatin were demonstrated in 96, 80, 62, and 42 tumors, respectively. When only the higher scores of cell frequency (3-5) were considered, PP and glucagon (accounting for 71 and 49 tumors, respectively) differed markedly from insulin (two tumors) and somatostatin (0). The frequency of PP-immunoreactive cells was higher in tumors of large size whereas that of glucagon cells was higher in the smaller neoplasms. No significant associations of the tumoral hormonal expressions were found with the type of histologic structure (trabecular versus gyriform), the occurrence of stromal fibrosis, and the intrapancreatic location of the neoplasms, except for a higher number of somatostatin cells in fibrotic tumors. Gastrin-immunoreactive cells never were found in the tumors in spite of the concomitant hypergastrinemia. In conclusion, the nonrandom expression of the hormonal phenotype by the neoplastic islet cells, as shown by the immunohistochemical, semiquantitative analysis of a large number of tumors, suggests that in our MEN-I patient the genetically determined neoplasms also are affected by other mechanisms, possibly nongenetic. PMID- 2895682 TI - Early damage of vascular endothelium during cardiac ischaemia. AB - To determine the site of reperfusion damage after ischaemia the leakage of xanthine dehydrogenase and xanthine oxidase was assessed in vascular and interstitial effluents. Contractile function was reduced during hypoperfusion but improved after the addition of superoxide dismutase and vasoxin to the perfusion medium. Both interstitial fluid and coronary effluent showed dehydrogenase and oxidase activity after no flow ischaemia. Furthermore, the ratio of lactate dehydrogenase to creatine kinase in coronary effluents was reduced. These findings indicate that the myocardial interstitium may be a site of ischaemic membrane damage since this space contains hypoxanthine and xanthine oxidase. The protective effect of superoxide dismustase also indicates the possibility of damage due to oxygen derived radicals in the cardiac interstitium during low flow perfusion. PMID- 2895683 TI - [Method of determining thyroid-stimulating immunoglobulins in the blood of patients with thyroid diseases]. PMID- 2895684 TI - The potential for transdifferentiation and regeneration of isolated striated muscle of medusae in vitro. PMID- 2895685 TI - Dynamic behavior of the transferrin receptor followed in living epidermoid carcinoma (A431) cells with nanovid microscopy. AB - Transferrin receptors labeled with the B3/25 monoclonal antibody-gold complexes were followed in living A431 cells by using video-enhanced contrast microscopy. Initially, the antibody-gold complexes bind to receptors which are freely mobile on the upper cell surface; they then become trapped at the inner margins of the peripheral lamellae and internalize. During endocytosis discrete gold-loaded vesicular elements first appear, and then, as they fuse, a heterogenous peripheral endosomal compartment forms. The endosomes from this compartment then begin to migrate centripetally through the cytoplasm in a saltatory way so that within 15 min gold label accumulates in a juxtanuclear endosome compartment. This compartment, which consists mainly of multivesicular bodies, is thus formed by the influx and retention of peripheral endosomal elements and their continued fusion in the juxtanuclear area. Although their overall migration is inward, saltating endosomes frequently reverse their direction of movement. As label builds up in the juxtanuclear area, small vesicles containing gold label continuously pinch off from the larger elements and migrate toward the cell periphery. Experiments with nocodazole and sodium azide show that the saltatory movements, the accumulation and retention of endosomes in the juxtanuclear area, and the separation of vesicles from endosomes are driven by a microtubule associated, ATP-dependent, motility-generating mechanism. Analysis of the movements shows that although each individual vesicle saltation can occur unpredictably toward the centre or the periphery of the cell, a net centripetal flux is observed. Moreover, it is evident that the probability of migration toward and maintenance in the juxtanuclear area is related to the diameter of the vesicles. We propose a mechanism by which bidirectional saltation along microtubules forming a radial network may be instrumental in the selective concentration of large endosomes in the juxtanuclear area while small vesicles are left free to return to the periphery. This process may be responsible for the sorting of receptors and ligands destined either for intracellular degradation in juxtanuclear lysosomes or, alternatively, for recycling to the plasma membrane. PMID- 2895686 TI - Axonal shortening and the mechanisms of axonal motility. AB - Axons in tissue culture retract and shorten if their tips are detached from the substrate. The shortening reaction of the axon involves contractile forces that also arise during normal axonal motility, elongation, and retraction. We studied shortening in axonal segments isolated from their parent axons by transecting the axon between the growth cone and the most distal point of adhesion to the substrate. Within 15-20 minutes after transection, an isolated axonal segment shortened and pulled its tail end toward the growth cone. During the shortening process, long sinusoidal bends arose along the axon. The identical shortening reaction occurs without transection, when the axon tip is detached from the substrate. Pharmacological studies with inhibitors of glycolysis indicate that the shortening mechanisms utilize metabolic energy, presumably ATP. The rate of sinusoidal shortening is similar to both the rate of polymer translocation in the axon by slow axonal transport and the rate of normal axonal elongation. Taxol inhibits the shortening reaction with a similar dose dependence to its inhibition of axonal growth. Together, all these observations suggest that the same basic intracellular motility mechanisms are involved in normal axonal growth, in slow axonal transport, and in the shortening reaction: the intracellular dynamic system that utilizes ATP to generate longitudinal movements of polymers within the axon may be the same mechanism underlying both the retraction and the elongation of the axon. PMID- 2895687 TI - [Behavior of TBII (TSH receptor binding immunoglobulins) in multinodular struma]. AB - The authors consider the behaviour of TBII (TSH receptor binding inhibitory immunoglobulins) in multinodular goiter, in relation to the functional status of the thyroid classified on the basis of T3, FT4, TSH IRMA. The samples were collected from 53 patients with normal T3, FT4 and TSH; 14 patients with T3 and FT4 in normal range and TSH less than 0.15 milli U/l; 8 patients with T3 and/or FT4 above the superior limits of normal range and TSH less than 0.15 milli U/l and from a control group of 10 patients with Grave's disease. TBII was measured by radioreceptor assay and the index resulted less than 15% in all the patients with eufunctioning or hyperfunctioning multinodular goiter. Mean value in biochemically hyperthyroid patients was 6.25% and in euthyroid patients was 5.69%. The difference was statistically not significant. Moreover, significantly elevated levels of TBII were found in 60% of patients with Grave's disease. PMID- 2895689 TI - Atracurium versus vecuronium: a comparison of recovery in outpatient arthroscopy. AB - Atracurium 0.5 mg.kg-1 and vecuronium 0.1 mg.kg-1 were compared as neuromuscular relaxants for outpatient arthroscopy of the knee under general anaesthesia. In 40 unpremedicated patients divided at random into two groups, anaesthesia was induced with methohexitone, atracurium (Group A) or vecuronium (Group B), three per cent isoflurane prior to intubation and 0.9 per cent during maintenance with nitrous oxide 66 per cent in oxygen. Neuromuscular function was recorded by a Datex Relaxograph. Recovery was assessed by the time the patients took to open their eyes, to be able to answer five questions correctly, the time to recovery of ocular balance (Maddox Wing test) and by comparing pre- and postoperative performance of a paper and pencil test (the p-deletion test). Recovery tests showed no significant differences between groups. After three hours all the patients were fit for discharge. The patients were interviewed one month after the procedure. All were satisfied with their anaesthetic. "Full recovery" took 1.5 days with a range of 1 h-7 days. The only significant difference (p less than 0.01) between the groups was the need for pharmacological reversal of residual paralysis. In a procedure with a mean duration of 45.6 minutes, and using isoflurane, all but one patient (95 per cent) in the atracurium group required neostigmine versus nine patients in the vecuronium group (45 per cent). PMID- 2895688 TI - A simple method for monitoring muscular relaxation during continuous infusion of vecuronium. AB - There is considerable individual variation in the dose of vecuronium required for the maintenance of surgical relaxation. Therefore to provide uninterrupted relaxation without overdosage it is advisable to regulate the IV infusion of vecuronium on the basis of appropriate monitoring. Monitoring with mechanomyography (MMG) or electromyography requires costly equipment and is too complex for routine clinical use. Visual observation of the adductor pollicis muscle contracting against zero resistance is not suitable for the reliable assessment of the degree of neuromuscular (NM) block. For clinical purposes satisfactory monitoring can be achieved with the simple device (Myoscan) described. The reliability of the Myoscan was tested in 30 patients by simultaneous monitoring of the force of contraction of the adductor pollicis on one side with the Myoscan and on the contralateral side with the MMG. Retrospective analysis of the MMG indicated that the conduct of anaesthesia would have been virtually the same if it would have been based on MMG monitoring. PMID- 2895690 TI - Effect of modifying agents on the phenotypic expression of cytochrome P-450, glutathione S-transferase molecular forms, microsomal epoxide hydrolase, glucose 6-phosphate dehydrogenase and gamma-glutamyltranspeptidase in rat liver preneoplastic lesions. AB - The expression of A and P forms of glutathione S-transferase (GST-A and P), two cytochrome P-450 isoenzymes (P-450 PB3a and P-450 MC2), microsomal epoxide hydrolase (mEHb), glucose-6-phosphate dehydrogenase (G6PD) and gamma glutamyltranspeptidase (gamma-GT) was compared in preneoplastic liver lesions and background parenchyma of F344 rats post-treated with butylated hydroxyanisole (BHA), ethoxyquin (EQ) or acetaminophen (AAP). These latter three compounds have been shown to inhibit hepatocarcinogenesis after initial treatment with N-ethyl-N hydroxyethylnitrosamine (EHEN) and a significant decrease in the number of enzyme altered foci and nodules positive for GST-P, GST-A, G6PD and gamma-GT and negative for P-450 PB3a, P-450 MC2 was associated with their administration. Whereas in the foci case the decrease was most prominent for non-discrete (heterogeneous) type lesions, the results of quantitation of nodules revealed a most significant alteration in the discrete homogeneously staining population. This indicates that BHA, EQ and AAP have the potential to inhibit the growth of the phenotypically stable lesions thought most likely to be the immediate precursors of hepatocellular carcinomas. The two anti-oxidants were associated with periportal increase of all enzymes investigated, whereas AAP induced GST species and mEHb in the perivenular zone. Irrespective of slightly elevated enzyme levels in surrounding parenchyma, mEHb antibody binding levels within lesions showed a reciprocal shift from positive to negative in rats treated with BHA, EQ and AAP. PMID- 2895691 TI - 2-Acetylaminofluorene promotion of liver carcinogenesis by a non-cytotoxic mechanism. AB - 2-Acetylaminofluorene (AAF), given in the diet at 0.02% for 4 weeks, is an effective promoter of liver carcinogenesis initiated by partial hepatectomy (PH) plus diethylnitrosamine (DEN) in the inbred rat strain Wistar Kyoto. AAF promotes the early (6 week) appearance of phenotypically altered (gamma glutamyltranspeptidase-positive) cells as well as the later appearance of neoplastic nodules (2-4 months) and hepatocarcinomas (4-8 months). Promotion does not seem to involve selective cytotoxicity (selection of AAF-resistant hepatocytes), since neither AAF alone nor DEN + AAF has any inhibitory effect on overall liver growth. PMID- 2895692 TI - Effect of choline-deficiency and methotrexate administration on peroxisomal beta oxidation, palmitoyl-CoA hydrolase activity and the glutathione content in rat liver. AB - Hepatic metabolism of long-chain fatty acids was studied in male rats fed a defined choline-deficient (CD) diet with and without choline and after methotrexate (MTX) administration. Peroxisomal beta-oxidation was increased approximately 4-fold in the peroxisome-enriched fraction of CD-fed animals, whereas the catalase activity was increased 1.3-fold. The urate oxidase activity was marginally affected. The CD-fed rats also revealed elevated capacity for hydrolysis of palmitoyl-CoA in the cytosolic fraction (2.0-fold), whereas the microsomal palmitoyl-CoA hydrolase activity was decreased. Notably, the increased peroxisomal beta-oxidation, the catalase activity and palmitoyl-CoA hydrolase activities (the membrane-bounded and cytosolic) were almost fully prevented by adding choline to the CD-diet. Thus, the change in these enzyme activities appears to be a consequence of a choline-deficiency provoked by the CD diet. MTX administration of normal fed rats (ND diet) had no effects on the peroxisomal beta-oxidation, catalase activity and urate oxidase activity. MTX treatment of the ND-fed animals, however, increased the mitochondrial palmitoyl-CoA hydrolase activity and decreased the microsomal enzyme activity. As choline-deficiency and MTX increased the hepatic lipid level, the overall results suggest that fat accumulation is not an 'induction signal' for increased peroxisomal beta oxidation. The CD diet alone increased the reduced glutathione content in liver, whereas MTX did not significantly change this level. Whether the changes of H2O2 generating peroxisomal oxidation of long-chain fatty acids may be an important step in a chain of events, which eventually results in tumour formation by choline-deficiency, should be considered. PMID- 2895693 TI - Lack of acetylaminofluorene--DNA adduct formation in enzyme-altered foci of rat liver. AB - Formation of the N-(deoxyguanosin-8-yl)-aminofluorene adduct was studied in enzyme-altered foci induced by four different liver carcinogenesis models. Foci were detected and scored for enzyme phenotype by a computer-aided image overlay technique. Localization of the enzymes gamma-glutamyl transpeptidase, canalicular ATPase and glucose-6-phosphatase was performed by enzyme histochemistry, allowing identification of foci of seven different phenotypes. Patterns of foci obtained by image overlay were compared to in situ 2-acetylaminofluorene--DNA adduct distribution obtained by immunofluorescence. Foci were induced by the following models: (1) chronic feeding of 0.02% 2-acetylaminofluorene (2-AAF) for 8 weeks; (2) intubation of diethylnitrosamine (DEN) (10 mg/kg) 24 h after a 70% partial hepatectomy (PH), followed 8 weeks later by a diet containing 0.05% phenobarbital for 9 months; (3) intubation of DEN (10 mg/kg) 24 h after PH, followed by a diet containing 0.01% ciprofibrate for 5 months, and after an additional 4 months a diet containing 0.05% phenobarbital for 2 months; (4) maintenance for 7.5, 16.5 or 19.5 months after transplantation of DEN/2-AAF/PH ('Solt-Farber' protocol) donor liver cells into host rats receiving a brief 2-AAF/PH selective regimen then no further treatment until sacrifice. To test the capacity of both foci and morphologically normal livers to form DNA adducts, the animals in models 2-4 received a diet containing 0.02% 2-AAF for 5 or 6 days before sacrifice. In all of the enzyme-altered foci identified in models 1-3 there were no DNA adducts visible by immunofluorescence. Scattered groups of positive cells were occasionally seen in the otherwise dark foci induced by model 4. For technical reasons some enzyme-altered foci were not identifiable on the fluorescence stained slides. In liver serial sections from rats in models 1-4, there were 75, 304, 125 and 68 enzyme-altered foci of seven different phenotypes which were identified as AF-DNA negative. In models 1 and 4 there were some additional adduct-negative foci not associated with any of the seven identified focus phenotypes. These studies demonstrate that loss of the ability to form DNA adducts in hepatic enzyme-altered foci is a common and very early biochemical adaptation to xenobiotic exposure in different hepatocarcinogenesis models. This adaptation also is retained by the majority of foci in later stages of hepatocarcinogenesis. PMID- 2895694 TI - Angiographic morphology and response to therapy in unstable angina. AB - The coronary anatomy of 69 patients with unstable angina, subgrouped according to response to medical therapy, was investigated. All patients received oral treatment with nitrates, calcium antagonists, and beta-blocking agents. When combined oral treatment was not effective, an intravenous infusion of nitrates (10-100 micrograms/min) was subsequently administered. Coronary arteriography was performed within hours (14 +/- 9 h) from the last episode of chest pain in 28 patients refractory to medical treatment, while in 41 patients who became asymptomatic during medical therapy, angiography was performed after an observation period of several days (8 +/- 6 days). On angiography, the nonresponder group was characterized by a prevalence of eccentric and multiple lesions, and by a 46% incidence of thrombi (p less than 0.001). Recurrent symptoms requiring emergency bypass operation were common in this group. In patients responsive to medical treatment, a high percentage of concentric lesions (37%) and totally occluded (34%) coronary arteries was found (p less than 0.05). No infarcts and low rate of recurrent angina were noted in these patients during hospitalization. In conclusion, the finding of intracoronary thrombotic material and eccentric or multiple lesions can be an accurate markers of the active phase of the disease, while "silent" occlusion of the involved vessel may be accompanied by relief of symptoms during medical therapy. PMID- 2895695 TI - Rapid changes in plasma potassium during a game of squash. AB - 1. The game of squash has recently been associated with a high incidence of ventricular arrhythmias and sudden death. To investigate this further, plasma catecholamines and potassium (K+) were monitored during a game of squash in six normal volunteers. 2. No cardiac arrhythmias were seen in this study despite the subjects reaching maximum heart rates of 181 +/- 5 beats/min (mean +/- SEM). 3. During exercise, plasma K+ rose from 3.82 +/- 0.16 to 4.29 +/- 0.2 mmol/l, but after 90 s rest this fell to 3.68 +/- 0.28 mmol/l and after 180 s to 3.44 +/- 0.17 mmol/l. This rapid K+ shift could not be accounted for by generalized changes in venous acid-base status or by changes in venous plasma catecholamines. Although pretreatment with a beta 2-antagonist caused the overall plasma K+ levels to be higher, it had no significant effect on the fall in plasma K+ after exercise. 4. Such rapid K+ shifts after exercise might contribute to arrhythmogenesis in susceptible individuals. The precise mechanism of the fall in K+ after exercise remains undetermined, but it seems not to involve catecholamines stimulating beta 2-adrenoceptors and is more likely to be due to increased skeletal muscle blood flow and/or intracellular acidosis. PMID- 2895696 TI - D-amino acid oxidase in mouse liver. AB - 1. An appreciable amount of D-amino acid oxidase was found in the extract of mouse liver by enzyme-linked immunosorbent assay (ELISA). 2. The content of the enzyme in the kidney and heart extracts was also measured by the assay. PMID- 2895697 TI - Mapping of the bcl-2 oncogene on mouse chromosome 1. AB - Two bcl-2 alleles have been identified in inbred strains of mice by restriction fragment length polymorphism (RFLP). Analysis of a bcl-2 RFLP in a series of bilineal congenic strains (C.D2), developed as a tool for chromosomal mapping studies, revealed linkage of bcl-2 to the Idh-1/Pep-3 region of murine chromosome 1. The co-segregation of bcl-2 alleles with allelic forms of two other chromosome 1 loci, Ren-1,2 and Spna-1, in a set of back-cross progeny, positions bcl-2 7.8 cM centromeric from Ren-1,2. PMID- 2895698 TI - Somatic cell mapping and restriction fragment analysis of bovine alpha and beta interferon gene families. AB - DNA from bovine x hamster hybrid cells preferentially segregating bovine chromosomes has been analyzed by blot hybridization with alpha and beta interferon probes. Retention or loss of bovine interferon genes was compared to segregation of bovine isozyme loci representing previously described syntenic groups. Families of bovine alpha (IFNA) and beta (IFNB) interferon genes were segregated in concordance with each other and with aconitase-1 (ACO1) on bovine syntenic group U18. This syntenic relationship is conserved on human chromosome 9p and on the portion of mouse chromosome 4 proximal to the centromere. In addition, cattle restriction fragment length polymorphisms were identified with both IFNA and IFNB probes. Of particular interest is a polymorphism apparently due to duplication of IFNB genes. PMID- 2895699 TI - [Mobile testes: report of 25 cases]. PMID- 2895700 TI - [Presence of a specific (not associated with the modification of currents in nerve endings) positive effect of K+ on the release of a mediator]. PMID- 2895701 TI - [Beta receptor blockers in coronary insufficiency and acute infarct. Pathophysiological bases]. PMID- 2895703 TI - [Diagnosis of hemophilia A and B by recombinant DNA methods]. PMID- 2895702 TI - The pathogenesis and management of schizophrenia. AB - Schizophrenia remains a relatively common debilitating and stigmatising disorder, whose precise aetiology is unknown. Research has consistently shown a strong genetic component, although environmental factors are also implicated. A number of biochemical aetiological theories have been proposed but the most plausible is the dopamine hypothesis. This suggests that there is excess activity at central dopaminergic pathways in the brain. Certainly, all effective antipsychotic drugs have dopamine blocking properties. Management of this disorder includes admitting new cases to hospital for careful evaluation by a multidisciplinary team. Although the mainstay of treatment is antipsychotic (neuroleptic) medication, social interventions are also required. These include close liaison with the patient's family, which can help to prevent relapse and aid compliance with drug treatment. Modern therapy aims for recovery of social and occupational skills and gradual rehabilitation back into the community. PMID- 2895704 TI - Detection of carcinogenic glutamic acid pyrolysis products in Worcestershire sauce by high-performance liquid chromatography. AB - Commercially available Worcestershire sauce was analyzed for mutagenic and carcinogenic glutamic acid pyrolysis products using high-performance liquid chromatography. These carcinogenic heterocyclic amines were found to be present in all brands of Worcestershire sauce analyzed. The identity of the carcinogens was confirmed by spectrometric analyses and the SOS umu-test. The concentrations of 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-amino dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2) in the Worcestershire sauce were 695 +/- 329 pmol/liter (mean +/- SD, n = 5) and 1,839 +/- 1,321 pmol/liter (n = 5), respectively. PMID- 2895705 TI - Temazepam versus flunitrazepam as an oral premedication in adult surgical patients. AB - In a randomized study, 20 patients received temazepam 20 mg orally the night before and 20 mg in the morning of an operation performed under spinal analgesia (Group I); 20 patients received flunitrazepam I mg similarly (Group 2). Different aspects of the premedication were evaluated verbally, with the aid of a visual analogue scale, Maddox wing apparatus, the critical flicker fusion threshold test, blood pressure and heart rate measurements, serum and CSF cortisol and plasma ADH measurements, as well as CSF drug level determinations. Clinically, temazepam 20 mg proved to be comparable with flunitrazepam I mg, although the latter more effectively prevented cardiovascular changes and pre-operative hormonal stress reaction. No correlation was found between the CSF drug level (bioassayed by radioreceptor assay) and the clinical response of the two benzodiazepines, nor was there any correlation between the cortisol or ADH levels versus the CSF drug levels. On the whole, flunitrazepam proved to be marginally better than temazepam as an oral premedicant. PMID- 2895706 TI - Topological and functional characterization of the F0I subunit of the membrane moiety of the mitochondrial H+-ATP synthase. AB - Using isolated polypeptides of the F0 sector of bovine heart mitochondrial H+ ATPase, antisera were developed detecting specifically two components of F0. These two components were identified as F0I and oligomycin-sensitivity-conferring protein (OSCP) respectively. Both F0I and OSCP were digested by mild trypsin treatment of submitochondrial particles depleted of the catalytic part of H+ ATPase (USMP). Proteolysis was largely prevented by binding of F1 to F0. Proteolysis of F0I resulted in the formation of three immunoreactive, membrane bound fragments of apparently 26 kDa, 25.5 kDa and 18 kDa, respectively, indicating that F0I contains trypsin-accessible Arg or Lys residues located close to the end and the middle part of the protein, respectively, which are in intimate contact with F1. Digestion of USMP with trypsin resulted in depression of passive H+ conduction through F0 which could be ascribed to proteolysis of F0I. PMID- 2895708 TI - The error in the cryptic stereospecificity of methylmalonyl-CoA mutase. The use of carba-(dethia)-coenzyme A substrate analogues gives new insight into the enzyme mechanism. AB - A preparation containing 80.0 +/- 0.5% (2RS)-methylmalonyl-carba-(dethia)-CoA and 20.0 +/- 0.5% propionyl-carba-(dethia)-CoA was reacted in buffered deuterium oxide with catalytic amounts of coenzyme B12, methylmalonyl-CoA mutase and methylmalonyl-CoA epimerase. The rearrangement of the methylmalonyl-carba (dethia)-CoA to succinyl-carba-(dethia)-CoA was monitored by recording 500-MHz 1H NMR spectra in short time intervals. After reaching equilibrium (approximately equal to 28 min) the products showed chemical stability for about 17 h, i.e. succinyl species did not undergo the spontaneous hydrolysis encountered with normal succinyl-CoA. In the pre-equilibrium stage only about 66% of the produced succinyl-CH2CoA was the expected monodeuterated species. The remainder was 15.5% unlabelled and 18.3% 3,3-dideuterated. After reaching equilibrium a continuous deuterium incorporation (washing-in) from the solvent to the products was observed and quantified. The time course of the appearance of unlabelled, mono-, di- and trideuterated succinyl-CH2CoA species was determined by assigning and integrating the isotope-shifted 1H signals from the various species. Furthermore, mutase catalyses slow deuterium incorporation into first the methylene and then the methyl group of propionyl-CH2CoA. On the basis of these data it was concluded that methylmalonyl-CoA mutase and epimerase are responsible for continuous deuterium incorporation and multiple incorporation occurs when the backward reaction (succinyl-CH2CoA----methylmalonyl-CH2CoA) becomes important. To account for all of the results obtained with dethia and natural substrates we propose a new mutase mechanism whereby the enzyme can retain full stereospecificity at C-3 of succinyl while an internal 1,2-H shift to give a C-2 succinyl radical is responsible for partial scrambling of diastereotopic protons at C-3. This mechanism successfully predicts the observed deuterium disproportionation in succinyl species and the order of appearance of di- and trideuterated products via the washing-in process. PMID- 2895707 TI - Reprogrammed expression of subunit 9 of the mitochondrial ATPase complex of Saccharomyces cerevisiae. Expression in vitro from a chemically synthesized gene and import into isolated mitochondria. AB - A synthetic gene has been designed and constructed by total chemical synthesis as a first step in the functional relocation from the mitochondrion to the nucleus of a gene encoding subunit 9 of the yeast mitochondrial ATPase complex. This gene (NAP9) incorporates codons frequently used in nuclear genes of Saccharomyces cerevisiae and additionally includes a series of unique restriction enzyme cleavage sites to facilitate future systematic manipulations of the gene and its protein product. Following the expression of the NAP9 gene by transcription and translation in vitro, a radiolabelled protein was produced which displayed a gel electrophoretic mobility and solubility in chloroform/methanol characteristic of the authentic subunit 9 proteolipid encoded in vivo by the mitochondrial oli1 gene. In order to achieve import into mitochondria of yeast subunit 9, a fusion was made between the NAP9 gene and DNA encoding the cleavable presequence of the nuclearly encoded precursor to subunit 9 from Neurospora crassa. Following expression in vitro, the resultant fusion protein was imported and appropriately processed by isolated yeast mitochondria. The import of yeast subunit 9 was less efficient than that observed in parallel import experiments with yeast subunit 8 attached to the same presequence or with the naturally occurring intact N. crassa subunit 9 precursor. Yeast subunit 9 lacking a leader sequence is not imported into mitochondria but, unlike subunit 8, it does not embed itself into the outer membrane, in spite of its highly hydrophobic character. PMID- 2895709 TI - Nifedipine and metoprolol in suspected unstable angina. Unstable angina pectoris. PMID- 2895710 TI - Nifedipine and metoprolol in suspected unstable angina. Review of other trials. PMID- 2895711 TI - Trends of HTLV-I and HIV infections in drug addicts. PMID- 2895712 TI - Immunoregulatory functions of paf-acether. II. Decrease of CD2 and CD3 antigen expression. AB - Paf-acether (platelet-activating factor) is a phospholipid initially described as a potent platelet-aggregating compound. It is produced by numerous cell types and is now considered as an important mediator of cell-cell interactions. The effect of paf-acether on the expression of CD2 and CD3, two human T cell surface glycoproteins, was investigated by indirect immunofluorescence and flow cytometry. Paf-acether partially down-regulated, in a time- and dose-dependent manner, CD2 and CD3 but not HLA class I antigen expression on peripheral human T cells and Jurkat cells. Lysophosphatidylcholine, a phospholipid closely related to paf-acether, had no detectable modulatory effect on CD2 and CD3 expression. In addition to CD2/CD3 modulation, paf-acether markedly inhibited T cell proliferative response not only to phytohemagglutinin or concanavalin A but also to anti-CD3 or a stimulatory combination of anti-CD2 monoclonal antibodies. These data demonstrate for the first time that lipid mediators such as paf-acether might be involved in the regulation of the expression of cell surface glycoproteins that are essential in the execution of T cell function. PMID- 2895713 TI - Faecal colonization with P-fimbriated Escherichia coli between 0 and 18 months of age. AB - A prospective study of faecal colonization with P-fimbriated Escherichia coli between 0 and 18 months of age was conducted in 751 healthy infants. The influence of breast-feeding and treatment with antibiotics on this colonization was studied. Colonization with P-fimbriated E. coli increased with age from 10% at 6 days to 30% at 18 months of age (P less than 0.01). Breast-feeding influenced colonization at 6 weeks of age when breast-fed children harboured fewer bacterial species (P less than 0.001) and fewer P-fimbriated E. coli (P = 0.06) than bottle-fed infants. Treatment with antibiotics increased the colonization rate with P-fimbriated E. coli at the age of 11 months (P less than 0.05). However, this was not true for treatment with ampicillin, which increased colonization rate with Gram-negative species other than E. coli (P less than 0.05). Fifty per cent (378) of all children were colonized and a quarter (183) had pure cultures of P-fimbriated E. coli in at least one faecal sample. The clinical importance of this colonization remains to be shown. PMID- 2895714 TI - [The hygiene of intellectual work]. PMID- 2895715 TI - [Periodical medical examinations--the 1st stage in dispensary care for workers]. PMID- 2895716 TI - [Feldsher Sergo (on the 50th anniversary of the death of G. K. Ordzhonikidze)]. PMID- 2895717 TI - [The feldsher's procedure in diseases of the teeth and jaws in the middle-aged and elderly]. PMID- 2895718 TI - Comparison of adrenergic agonist and insulin effects on 3-O-methyl-D-glucose efflux and sarcolemmal cytochalasin B binding by perfused rat heart. AB - 1. alpha- and beta-Adrenergic agonists as well as insulin stimulate 3-O-methyl-D glucose efflux by the perfused rat heart and increase D-glucose inhibitable cytochalasin B binding by isolated sarcolemma. 2. alpha- and beta-Agonists like insulin increase Vmax for 3-O-methyl-D-glucose efflux and increase Bmax for cytochalasin B binding. 3. The effects of alpha- and beta-agonists are totally Ca2+-dependent whilst those of insulin appear to be only partly Ca2+-dependent. PMID- 2895720 TI - Post-transcriptional regulation of a murine homeobox gene transcript in F9 embryonal carcinoma cells. AB - A 2.4 kb RNA encoded by the murine Hox 1.1 (m6) homeobox gene is induced when F9 stem cells are differentiated with retinoic acid and dibutyryl cyclic AMP. The regulation of Hox 1.1 expression was probed by using cycloheximide, an inhibitor of protein synthesis. Production of the Hox 1.1 RNA in differentiating F9 cells was not blocked by treatment with cycloheximide, indicating that new protein synthesis is not required for its induction. On the contrary, this transcript was detected in F9 stem cells treated with cycloheximide, anisomycin, or emetine alone. Nuclear transcription assays indicated that the Hox 1.1 gene was transcribed in F9 stem cells and that the rate of transcription did not change early in the differentiation of F9 cells. These observations indicate that the induction of Hox 1.1 transcripts in F9 stem cells during differentiation is not regulated at the level of transcription initiation but results from stabilization of the transcript. PMID- 2895719 TI - Somatostatin release from dispersed hypothalamic cells: effects of diabetes. AB - We examined the release of growth hormone-release inhibiting factor (somatostatin) from dispersed hypothalamic cells obtained from mature diabetic rodents and normal age-matched controls, in an attempt to demonstrate a possible hypothalamic defect which might underlie some of the reported abnormalities in somatotrophic function in diabetes mellitus. Insulinopoenic diabetes was induced by either streptozotocin or alloxan. Somatostatin release from cells from diabetic rats was diminished both basally and after stimulation by membrane depolarisation. Stimulated release was calcium dependent in cells from both normal and diabetic animals. The defect was present in both streptozotocin and alloxan induced diabetes. We also compared hypothalamic somatostatin release from cells obtained from obese hyperinsulinaemic C57 BL/Ks db/db diabetic mice and non diabetic lean litter mates (db/-). Despite longstanding marked hyperglycaemia, no significant alteration in somatostatin release was apparent. Likewise, starvation of rats for 5 days did not result in significant diminution of somatostatin release. These observations document a defect in hypothalamic somatostatin release in experimentally induced insulinopoenic diabetes, which is not apparent in the db/db mouse, suggesting that glucose per se is not responsible. Rather than the anticipated increase in hypothalamic somatostatin release in insulinopoenic diabetes, a reduction in release was observed. These observations are compatible with the hypothesis that increased hypothalamic somatostatin release is not responsible for abnormal growth hormone secretion in this model. PMID- 2895721 TI - Development of enzymic zonation in liver parenchyma is related to development of acinar architecture. AB - The appearance of the distribution patterns of the NH3-metabolizing enzymes carbamoylphosphate synthetase, glutamate dehydrogenase, and glutamine synthetase in the developing liver of an altricial species (rat) was compared with that in the developing liver of a closely related, precocial species (spiny mouse). The comparison showed that the development of hepatic acinar architecture, rather than perinatal adaptation, is responsible for the development of periportal and pericentral compartments of gene expression. Conditions that confine the expression of specific enzymes to the pericentral compartment of the acinus originate before conditions that confine the expression of (other) specific enzymes to the periportal compartment. However, whether or not the site of gene expression is restricted to specific compartments within the liver acinus, the rate of expression of the gene involved can also be adaptively regulated. Therefore, different factors appear to control the site and the rate of gene expression within one tissue. PMID- 2895722 TI - Effect of disodium cromoglycate (DSCG) and antihistamines on postirradiation cerebral blood flow and plasma levels of histamine and neurotensin. AB - In an attempt to elucidate mechanisms underlying the irradiation-induced decrease in regional cerebral blood flow (rCBF) in primates, hippocampal and visual cortical blood flows of rhesus monkeys were measured by hydrogen clearance, before and after exposure to 100 Gy, whole-body, gamma irradiation. Systemic blood pressures were monitored simultaneously. Systemic arterial plasma histamine and neurotensin levels were determined preirradiation and postirradiation. Compared to control animals, the irradiated monkeys exhibited an abrupt decline in systemic blood pressure to 23% of the preirradiation level within 10 min postirradiation, falling to 12% by 60 min. A decrease in hippocampal blood flow to 32% of the preirradiation level was noted at 10 min postirradiation, followed by a slight recovery to 43% at 30 min and a decline to 23% by 60 min. The cortical blood flow for the same animals showed a steady decrease to 29% of the preirradiation levels by 60 min postirradiation. Animals given the mast cell stabilizer disodium cromoglycate and the antihistamines mepyramine and cimetidine before irradiation did not exhibit an abrupt decline in blood pressure but displayed a gradual decrease to a level 33% below preirradiation levels by 60 min postirradiation. Also, the treated, irradiated monkeys displayed rCBF values that were not significantly different from the nonirradiated controls. The plasma neurotensin levels in the irradiated animals, treated and untreated, indicated a nonsignificant postirradiation increase above control levels. However, the postirradiation plasma histamine levels in both irradiated groups showed an increase of approximately 1600% above the preirradiation levels and the postirradiation control levels. These findings implicate histamine in the postirradiation hypotension, but not necessarily in the direct responsibility for the decrease in regional cerebral blood flow seen immediately postirradiation in the primate. PMID- 2895724 TI - [Effect of glutamic acid and potassium iodide on the course of experimental pneumoconiosis caused by coal and nepheline]. PMID- 2895723 TI - Pattern of transcription of the homeo gene Hox-3.1 in the mouse embryo. AB - A cDNA from the Hox-3.1 locus, isolated from a 10.5-day postcoitum (p.c.) mouse embryo cDNA library, and the putative encoded protein are described. The spatial distribution of Hox-3.1 gene transcripts from late gastrulation to embryonic day 14.5 p.c. was monitored by in situ hybridization, using a cDNA probe. When first detectable in 8.5-day p.c. embryos, the transcripts are distributed in all the tissues of the posterior end. At later stages, the distribution becomes progressively spatially restricted and tissue specific. By 12.5 days p.c., transcription is localized most intensely in the neural tube region lying above the heart. The early transcription pattern thus appears to be compatible with a regionalizing role for the Hox-3.1 gene. PMID- 2895725 TI - [Prediction of the clinical efficacy of neuroleptics in the treatment of acute schizophrenic psychoses by assessment of the phenomenon of appearance of plaque in the blood]. PMID- 2895726 TI - [The effect of atropine, Hi-6 and diazepam on the levels and metabolism of monoamines in the brain of rats poisoned with VX]. PMID- 2895728 TI - Patterns of polymorphism and linkage disequilibrium for cystic fibrosis. AB - Four polymorphic markers that map within 80 kb of an HTF island which is genetically very close to the cystic fibrosis locus have been identified. We have analyzed the linkage disequilibrium between each of these markers and the cystic fibrosis mutation in 89 families from four European countries, Denmark, Finland, Spain, and Great Britain. Strong linkage disequilibrium between three polymorphic sites and cystic fibrosis was observed. The markers on the J3.11 (D7S8) side of the HTF island show stronger disequilibrium than those on the met side. Linkage disequilibrium between markers and disease alters the probability that a person of a given haplotype is a carrier in some populations and helps to identify regions of a sequence that are most likely to contain the cystic fibrosis mutation. PMID- 2895727 TI - Linkage, physical mapping, and DNA sequence analysis of pseudoautosomal loci on the human X and Y chromosomes. AB - The pseudoautosomal region of the human X and Y chromosomes is subject to frequent X-Y recombination during male meiosis. We report the finding of two pseudoautosomal loci, DXYS20 and DXYS28, characterized by highly informative restriction fragment length polymorphisms (RFLPs). The pseudoautosomal character of DXYS20 and DXYS28 was formally demonstrated by comparing their transmission to 45,X and to normal individuals. Studies of the inheritance of these loci reveal that the pseudoautosomal region, though highly recombinogenic, is subject to marked recombinational interference in male meiosis; no double recombinants were observed in 143 triply informative meioses, and the coefficient of coincidence is likely less than 0.45. In female meiosis, linkage of these pseudoautosomal RFLPs to strictly sex-linked RFLPs on the short arm of the X is readily detected; the genetic length of the pseudoautosomal region in female meiosis is at least 4 cM but not more than 18 cM. The genetic map of the human X chromosome is now defined from near the short-arm telomere to band q28 on the long arm. Locus DXYS20, which maps near the X and Y short-arm telomeres, is composed of long tandem arrays of 61-bp repeats. Occasional, seemingly random base-pair substitutions within these arrays of 61-bp repeats, in combination with marked variation in the size of the array, generate the high degree of DNA polymorphism at DXYS20. PMID- 2895729 TI - Mapping of the mouse fibronectin gene (Fn-1) to chromosome 1: conservation of the Idh-1-Cryg-Fn-1 synteny group in mammals. AB - Restriction fragment length polymorphisms (RFLPs) were observed in BamHI-digested mouse DNA probed with a cDNA for human fibronectin. Analysis of the inheritance of fibronectin RFLPs in AKXD and SWXJ recombinant inbred strains of mice mapped the locus, Fn-1, to the midregion of mouse chromosome 1 about 4 cM distal from the loci encoding gamma-crystallins (Cryg). Loci homologous to genes in the centromeric third of mouse chromosome 1 are also syntenic in rats, humans, and cattle and may, therefore, mark a large conserved chromosomal segment of the mammalian genome. PMID- 2895730 TI - Relationship of the genes for Chediak-Higashi syndrome (beige) and the T-cell receptor gamma chain in mouse and man. AB - The genetic linkage of Chediak-Higashi syndrome and its murine analog, beige (bg), to the T-cell receptor (TCR-gamma) gamma chain gene is further defined. Previous studies using recombinant inbred strains of mice demonstrated that the murine bg gene is genetically linked to a murine TCR-gamma gene. We report that in the mouse the frequency of recombination between these two markers is 0.025. Further, we tested the hypothesis that these two genes are linked in the human genome by analyzing restriction fragment length polymorphisms (RFLPs) in five families with children afflicted with Chediak-Higashi syndrome. In three families, RFLPs in TCR-gamma genes were inherited discordantly from Chediak Higashi syndrome, demonstrating nonlinkage. We postulate that there is an evolutionary chromosomal breakpoint between the bg gene and the TCR-gamma gene. PMID- 2895731 TI - Failure of long-acting, recently-introduced B-agonists in asthma. PMID- 2895732 TI - Sequential activation and loss of the pre-B cell Thy-1 gene in T-cell X pre-B cell somatic hybrids. AB - In somatic cell hybrids between the pseudodiploid Thy-1- Abelson-leukemia-virus induced pre-B cell lymphoma RAW 253.1 and the Thy-1+ T-cell lymphoma, AKR1 (Thy 1+), all cells express the Thy-1 allele of the T-cell parent but most hybrid cells do not express the Thy-1 allele of the pre-B cell lymphoma parent. The Thy 1 allele of the pre-B cell parent, however, is spontaneously activated in a minor proportion of hybrid cells. By sorting for cells expressing the Thy-1 allele of the pre-B cell parent, derivative clones in which 100% of cells express both parental Thy-1 alleles can be isolated. Revertants with a phenotype identical with that of the original hybrid cell line can be isolated from these derivatives by sorting for nonexpression of the Thy-1 allele of the pre-B cell parent. These first-generation revertant cell lines have lost one copy of the Thy-1 gene derived from the pre-B cell lymphoma parent. By a further cycle of sorting, derivatives in which 100% of cells express both parental Thy-1 alleles can again be obtained. Second-generation revertants isolated by sorting these Thy-1+ hybrid cells for nonexpression of the Thy-1 allele of the pre-B cell parent no longer contain a normal copy of the pre-B cell Thy-1 allele and this surface antigen is no longer expressed by any cells in the population. These results are consistent with a mechanism that sequentially activates each copy of the Thy-1 gene derived from the pre-B cell lymphoma parent. Hybrids between the class D Thy-1- mutant, AKR1 (Thy-1- d), in which the 5' region of the Thy-1 structural gene has been deleted, and RAW 253.1 cannot be activated to express either Thy-1 allele. This result indicates that a sequence upstream of exon 2 of the active Thy-1 allele is critical for the initial activation event. PMID- 2895733 TI - T-cell receptor and HLA class II RFLPs in systemic lupus erythematosus. PMID- 2895734 TI - Mapping of the Ly-4 (L3T4) T-cell differentiation antigen on mouse chromosome 6 by the use of RFLPs in an interspecific cross. PMID- 2895735 TI - Sodium responsiveness of central alpha 2-adrenergic receptors in spontaneously hypertensive rats. AB - The responsiveness of central nervous system alpha 2-adrenergic receptors in the neural control of renal function was compared in conscious spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) on normal or high sodium intake (3-4 weeks of 1% NaCl for drinking). The responsiveness of central alpha 2-adrenergic receptors was determined by comparing among groups the dose-response curves for the effects of cumulative intracerebroventricular injections of guanabenz (5, 25, and 125 micrograms) on changes in mean arterial pressure, renal sympathetic nerve activity, and urinary sodium excretion. Guanabenz altered mean arterial pressure similarly in SHR on normal or high sodium intake and in WKY on normal or high sodium intake. High sodium intake shifted the guanabenz-renal sympathetic nerve activity and guanabenz-urinary sodium excretion dose-response curves to the left in SHR and to the right in WKY. The dose-response curves between SHR and WKY on normal sodium intake were similar. Surgical renal denervation or pretreatment with an alpha 2-adrenergic receptor antagonist (rauwolscine, 30 micrograms i.c.v.) attenuated the ability of guanabenz to inhibit renal sympathetic nerve activity or increase urinary sodium excretion in SHR and WKY on either normal or high sodium intake. We conclude that the responsiveness of central nervous system alpha 2-adrenergic receptors regarding the neural control of renal function is increased by high sodium intake in conscious SHR, but not in conscious normotensive WKY. PMID- 2895736 TI - Direct effects of alpha 2-adrenergic receptor stimulation on intravascular systemic capacity in the dog. AB - The role of alpha 2-adrenergic receptor stimulation in the regulation of systemic vascular capacity and venous return, a major determinant of cardiac output, is not well understood. With the influence of the central nervous system isolated from the systemic circulation, the direct peripheral vascular effects of two specific, chemically distinct alpha 2-adrenergic receptor agonists, UK 14,304 and B-HT 920, were investigated in 19 dogs on total cardiopulmonary bypass with constant arterial perfusion and central venous pressure. Five-minute intra arterial infusions of UK 14,304 (200 micrograms/min) resulted in increased arterial resistance (mean arterial pressure increased 18 +/- 4 [SEM] mm Hg; p less than 0.01) and a decrease in systemic vascular capacity (81 +/- 20 ml; p less than 0.01). This decrease in systemic vascular capacity appears to result from vasoconstriction, since there was no decrease in transhepatic resistance to portal flow and no significant change in hepatic vein flow to suggest redistribution of arterial blood flow. Yohimbine abolished both the arterial and systemic capacity effects, whereas prazosin did not. Intra-arterial administration of B-HT 920 (200 theta grams/min) in five dogs produced similar changes in arterial resistance and systemic capacity. These findings provide direct evidence for beta 2-adrenergic control, not only of arterial resistance but also of systemic vascular capacity, which in the intact animal would increase venous return to the heart. PMID- 2895737 TI - Effects of arterial vasodilators on cardiac hypertrophy and sympathetic activity in rats. AB - In spontaneously hypertensive rats (SHR), the progression (or absence of regression) of cardiac hypertrophy despite adequate blood pressure (BP) control by arterial vasodilators has been attributed to increased cardiac sympathetic activity. We evaluated changes in indices of general and cardiac sympathetic tone in relation to changes in cardiac anatomy during treatment of normotensive rats and SHR with hydralazine, 120 mg/L, or minoxidil, 120 mg/L of drinking water. In SHR, both vasodilators reduced BP rapidly and consistently. Significant increases in heart rate and plasma norepinephrine were observed only in the initial 2 days of arterial vasodilator treatment. After 5 weeks of treatment, marked increases in left and right ventricular sympathetic activity (as assessed by norepinephrine turnover rates) were present, but no increase was seen in heart rate and plasma norepinephrine. Intravascular volume expansion was observed on Day 14 of minoxidil and Day 35 of hydralazine treatment. Prolonged treatment with minoxidil induced significant increases in left ventricular internal diameter, as well as in left and right ventricular weights, but not in the wall thickness of the left ventricle. Treatment with hydralazine did not affect left ventricular weight and caused a small increase in the weight of the right ventricle. In normotensive rats, both vasodilators initially decreased BP, but tolerance developed within 1 to 2 weeks of treatment. Plasma norepinephrine and heart rate showed increases only at Day 1 of either treatment, whereas cardiac sympathetic hyperactivity persisted at 2 and 5 weeks of treatment. Changes in cardiac anatomy were qualitatively similar to those observed in SHR. We conclude that, during treatment of normotensive rats and SHR with arterial vasodilators, cardiac sympathetic hyperactivity persists and may be involved in the cardiac effects of arterial vasodilators. However, other mechanisms, such as chronic cardiac volume overload, may also play an important role, particularly with minoxidil. PMID- 2895738 TI - Hyperadhesive mutant of type 1-fimbriated Escherichia coli associated with formation of FimH organelles (fimbriosomes). AB - The relationships of the genes and gene-products mediating D-mannose-specific attachment of type 1 fimbriae of Escherichia coli to eucaryotic cells were investigated by deletion mutation analysis of recombinant plasmid pSH2, which carries the genetic information for the synthesis and expression of functional type 1 fimbriae. Mutant pUT2004 was derived by a deletion remote from the structural gene encoding the 17-kilodalton (kDa) subunit protein of type 1 fimbriae. Phenotypically, the mutant demonstrated an eightfold-higher mannose specific hemagglutination titer than the parent strain. On electron microscopy, the mutant strain expressed the same number of fimbriae as the parent strain. However, numerous 10-nm-diameter rounded structures (fimbriosomes) were observed both closely associated with fimbriae and in the culture medium. Fimbriosomes isolated from the medium agglutinated guinea pig erythrocytes in a mannose sensitive manner. Dissociation of the fimbriosomes yielded a single 29-kDa protein, as demonstrated by sodium dodecyl sulfate gel electrophoresis. Antibodies raised against fimbriosomes reacted with a 29-kDa protein on immunoelectroblots of dissociated type 1 fimbriae and also blocked the adherence of other strains of type 1 fimbriated E. coli to eucaryotic cells. These findings suggest that the enhanced adhesive properties of the mutant pUT2004 strain are associated with overproduction of the 29-kDa FimH in the form of fimbriosomes which contain the determinant of the D-mannose-sensitive adhesion of type 1 fimbriae. PMID- 2895739 TI - Structural and serological relatedness of Haemophilus influenzae type b pili. AB - The structural and serological relatedness of the pilus proteins of several isolates of Haemophilus influenzae type b cultured from patients with invasive disease and from different anatomic sites within the same patient was examined. Epithelial cell-adherent variants of 25 nonadherent parent isolates were obtained by selection for organisms that adhered to human erythrocytes. Outer membrane protein analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the presence of an additional 24- to 24.5-kilodalton protein among all adherent variants but absent from all nonadherent parent isolates. Polyclonal rabbit antiserum against the intact native pilus protein of H. influenzae M43 cross-reacted with 20 of 25 adherent H. influenzae in both immunodot and slide agglutination assays. No differences in reactivity among isolates cultured from more than one anatomic site in the same patient were noted. Anti-M43 pilus antiserum had bactericidal activity against both the homologous strain and a heterologous strain that demonstrated serologic identity in the immunodot and slide agglutination assays. The adherence of these strains to human epithelial cells in vitro was inhibited by Fab fragments purified from the antipilus antiserum. These data indicate that a remarkable degree of homogeneity in pilin subunit size exists among the pili of H. influenzae type b and that major antigenic determinants are shared among most of these pili. Also, antibodies directed against H. influenzae pilus proteins may be able to contribute to host defenses through serum bactericidal activity and by blocking the adherence of this bacterium to host epithelial cells. PMID- 2895740 TI - A hemagglutinin of uropathogenic Escherichia coli recognizes the Dr blood group antigen. AB - A receptor moiety and blood group substance recognized by the O75X adhesin was studied. Well-defined erythrocytes representing different blood group systems and bacterial derivatives carrying plasmid pBJN406 encoding the adhesin were used in a direct hemagglutination assay. We showed that Dr blood group antigen, a component of the IFC blood group complex, is the receptor for the O75X fimbrialike adhesin (Dr hemagglutinin) of uropathogenic Escherichia coli. The molecule recognized by the Dr hemagglutinin on Dr blood group substance is a chloramphenicol-like structure. The inhibitory effect of the active compounds indicates that a tyrosine-containing molecule could be a natural receptor for the Dr hemagglutinin. Dr blood group substance was found in tubular basement membrane and Bowman's capsule of the human kidney. Specific attachment of a Dr hemagglutinin-positive bacterial strain to the kidney substructures was inhibited by chloramphenicol. PMID- 2895741 TI - Inhibitors of receptor-mediated endocytosis block the entry of Bacillus anthracis adenylate cyclase toxin but not that of Bordetella pertussis adenylate cyclase toxin. AB - Bordetella pertussis and Bacillus anthracis produce extracytoplasmic adenylate cyclase toxins (AC toxins) with shared features including activation by calmodulin and the ability to enter target cells and catalyze intracellular cyclic AMP (cAMP) production from host ATP. The two AC toxins were evaluated for sensitivities to a series of inhibitors of known uptake mechanisms. Cytochalasin D, an inhibitor of microfilament function, abrogated the cAMP response to B. anthracis AC toxin (93%) but not the cAMP response elicited by B. pertussis AC toxin. B. anthracis-mediated intoxication of CHO cells was completely inhibited by ammonium chloride (30 mM) and chloroquine (0.1 mM), whereas the cAMP accumulation produced by B. pertussis AC toxin remained unchanged. The block of target cell intoxication by cytochalasin D could be bypassed when cells were first treated with anthrax AC toxin and then exposed to an acidic medium. These data indicate that despite enzymatic similarities, these two AC toxins intoxicate target cells by different mechanisms, with anthrax AC toxin entering by means of receptor-mediated endocytosis into acidic compartments and B. pertussis AC toxin using a separate, and as yet undefined, mechanism. PMID- 2895742 TI - Characterization of P fimbriae on O1, O7, O75, rough, and nontypable strains of Escherichia coli. AB - P fimbriae of 37 uropathogenic Escherichia coli O1:K1, O7:K1, O22, O75, rough:K1, and nontypable strains were characterized by immunoprecipitation with 14 fimbria specific rabbit antisera. The fimbrial composition of these strains, as reflected by the apparent molecular weights of the fimbrial peptides, was correlated with the O serogroup of the strains, but serological cross-reactivity of P fimbriae of different E. coli serogroups was frequently observed. The genetic clonal relationships of the strains were analyzed by determining the electrophoretic types, based on 18 chromosomally encoded enzymes. Among the O1:K1 strains, the same P-fimbrial variants occurred on strains that were either closely related or very distinct in their electrophoretic types, indicating that the P fimbriae have evolved in association with the O and K antigens. In contrast, certain O7:K1 and R:K1 strains as well as some O22 and O75 strains were genotypically identical and shared similar P-fimbrial variants, which differed serologically from those of other E. coli serogroups. Our results show that, despite the structural variability seen in electrophoretic analysis of P fimbriae of different serogroups, many P-fimbrial variants share common antigenic determinants that are recognized by rabbit antisera. Based on immunoprecipitation analyses, three anti P-fimbria sera have now been identified that react with P fimbriae of 82 of 84 uropathogenic E. coli strains characterized in Finland. PMID- 2895743 TI - Bacterial activation of human natural killer cells: role of cell surface lipopolysaccharide. AB - Culture of human peripheral blood lymphocytes with gram-negative bacteria associated with periodontal disease caused a rapid increase in the cytotoxic potential of natural killer (NK) cells. The NK cells were activated to kill NK resistant targets, the peak cytotoxicity occurring on day 1 of culture. The addition of anti-Tac, anti-CD3, or anti-OKT-11 antibodies to block activation via the interleukin-2 (IL-2), T-cell, or E rosette receptors had a minimal effect on this inductive process. Anti-IL-2 antiserum was effective in blocking a significant amount, but not all, of the cytotoxicity in bacterium-activated cultures. Modest IL-2 production (5 to 6 National Institutes of Health units) was measured in lymphocyte cultures activated by bacteria, but proliferation was not induced during a 1-week period. When polymixin B sulfate was added to bind and block lipopolysaccharides, bacterium-induced cytotoxicity was completely abrogated for all activating bacteria. In addition, when culture supernatants from Actinobacillus actinomycetemcomitans were tested, activation still occurred. However, again, this activation was totally inhibited by polymixin B sulfate. Monocytes were also activated by bacteria to produce tumor necrosis factor (TNF). To exclude the possibility that TNF was responsible for cytotoxicity, an antiserum to TNF was added to cocultures of bacteria and lymphocytes with adherent cells removed. The antiserum had no effect on the inductive process. In addition, exogenous TNF did not kill M14 targets. These results suggest that bacterial cell surface lipopolysaccharides provide a major activation signal for NK cells to enhance cytotoxicity. PMID- 2895744 TI - Induction of inflammation by Escherichia coli on the mucosal level: requirement for adherence and endotoxin. AB - Bacterial infection of the mouse urinary tract is followed by the recruitment of leukocytes to the mucosal surface. This study examined the bacterial components involved in the induction of this response. Escherichia coli of serotype O75:K5:H expressing adhesins specific for the Gal alpha 1-4Gal beta- (Gal, galactose) and mannose-containing receptors were instilled into the urinary bladder of lipopolysaccharide responder (C3H/HcN) and lipopolysaccharide nonresponder (C3H/HeJ) mice. The inflammation was quantitated as the number of leukocytes excreted into the urine at various times after infection. The response was first shown to depend on the Lps genotype of the mouse. The leukocyte excretion that occurred within 24 h after infection of C3H/HeN mice was absent in C3H/HeJ mice. The components triggering the response were present on both live and Formalin killed bacterial cells, and the response was mimicked by intravesical inoculation of isolated lipid A. Pretreatment of bacteria with soluble receptor oligosaccharides resulted in inhibition of attachment in vitro and of the inflammation in vivo. A direct synergy between adhesins specific for Gal alpha 1 4Gal beta receptors and lipid A was demonstrated. Mixtures of these components induced a leukocyte response higher than the sum of the responses to each component alone. These results suggest that the inflammation induced by gram negative bacteria in the urinary tract can be triggered at the level of the epithelial cells by endotoxin presented by an attaching bacterial cell and that intact function at the Lps locus of the host is required for this to occur. PMID- 2895745 TI - Identification of a human erythrocyte receptor for colonization factor antigen I pili expressed by H10407 enterotoxigenic Escherichia coli. AB - We have identified a receptor for colonization factor antigen I (CFA/I) pili in human erythrocyte membranes. Erythrocyte binding assays, using whole organisms, suggested that the CFA/I receptor was a glycoprotein containing important sialic acid moieties. Subsequently, human erythrocyte membranes were extracted with lithium diiodosalicylate to obtain a soluble glycoprotein fraction from which to isolate receptors. The extracted material caused agglutination of the CFA/I+ but not the CFA/I- organisms at a protein concentration of 0.5 mg/ml. The CFA/I receptor was identified in iodinated extract by an affinity isolation procedure, using whole bacterial cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography of the washed, extract-coated H10407 CFA/I+ organisms revealed a band with an apparent molecular weight of 26,000 which was present in the original extract but was not observed on extract-coated H10407 CFA/I- bacteria. The addition of purified CFA/I pili reduced binding of the 26,000-molecular-weight receptor to CFA/I+ bacteria. The CFA/I-specific receptor species also bound to wheat germ agglutinin-agarose. This observation supported the suggestion that the CFA/I receptor identified in this report is a sialoglycoprotein. PMID- 2895746 TI - Protective antigens against enterotoxigenic Escherichia coli O101:K99,F41 in the infant mouse diarrhea model. AB - Protective antigens present in whole cells of bovine enterotoxigenic Escherichia coli strains were tested in an infant mouse diarrhea model. Reduction of mortality rates of infant mice suckling vaccinated mothers was measured 1, 2, and 5 days after oral challenge with strain B41 (O101:K99,F41:H-). Vaccines consisted of strains of serogroup O101, O9, O8, or O20 and of variants bearing or not bearing antigens K99 and F41. K99 and F41 expressions were checked by slide agglutination with K99 and F41 antisera and by mannose-resistant microhemagglutination with horse, sheep, and guinea pig erythrocytes. Absence of production of K99 antibodies following hyperimmunization with K99-negative variants was established in rabbit antisera. Strains bearing K99 alone induced less protection of infant mice 5 days after challenge than strains bearing F41 alone or both K99 and F41. Absence of expression of K99 in the vaccinal strains resulted in either a slight decrease (strains bearing additional F41) or complete abolishment (strains bearing K99 alone) of protection. Failure of F41 synthesis by O101 strains or variants resulted in no protection 5 days after challenge. F41 probably also supplied most of the protection induced by the O9 strain. When negative for both K99 and F41, strains of serogroup O101 still provided protection 1 and 2 days after challenge. This protection was also induced by strain H510a, the reference for O101 antigen. Thus, O antigen contributed to the best vaccinal protection, in addition to K99 and F41. PMID- 2895747 TI - Effects of AHR-5333, a new potential antiallergy compound, in in vivo models of immediate hypersensitivity. AB - AHR-5333 [1-[4-[3-[4-[bis(4-fluorophenyl)hydroxymethyl]-1-piperidinyl] propoxy]-3 methoxyphenyl]ethanone] possessed potent, long-acting activity in rat and guinea pig in vivo models of immediate hypersensitivity: AHR-5333 was more potent than azatadine (2 X), ketotifen (approximately 3 X), oxatomide (approximately 5 X), albuterol (6 X) and aminophylline (approximately 50 X) in a passive, foot anaphylaxis model in rats and more potent than diphenhydramine (approximately 237 X), oxatomide (approximately 5.6 X) and theophylline (approximately 295 X) in guinea pigs challenged with aerosolized antigen. A long duration of action was noted after oral dosing of guinea pigs (24 h PD50, 0.78 mg/kg). Administration by aerosol (1%) to sensitized, spontaneously breathing, conscious guinea pigs protected against antigen-induced anaphylactic collapse; this protection persisted through 8 h. When administered prior to antigen challenge, AHR-5333 (10 mg/kg, p.o.) effectively inhibited ascaris antigen-induced skin hypersensitivity reactions in both dogs and cynomolgus monkeys. PMID- 2895748 TI - The third nation-wide study on adult T-cell leukemia/lymphoma (ATL) in Japan: characteristic patterns of HLA antigen and HTLV-I infection in ATL patients and their relatives. The T- and B-cell Malignancy Study Group. AB - To clarify the intrinsic factors involved in the manifestation of adult T-cell leukemia/lymphoma (ATL) in Japan, a third nation-wide study on ATL was conducted by the T- and B-cell Malignancy Study Group. General clinico-epidemiological findings on ATL and infectious modes of transmission of human T-lymphotropic virus type I (HTLV-I) from 181 ATL patients and their relatives were analyzed and the frequency of HLA antigens in 64 ATL patients was compared with that of 48 relatives of ATL probands, 340 controls from all Japan and 236 controls from Kyushu (Tanaka et al., 1984). General findings on ATL were mostly the same as those in the 2 previous nation-wide studies. The age-specific positivity rate of anti-HTLV-I antibody in siblings of ATL patients was markedly higher than that in children of ATL patients. This suggests that there is a high risk of mothers of ATL patients transmitting HTLV-I to their children who may develop clinical ATL after reaching ATL risk age. Frequencies of HLA antigens A26 and B39, among patients with ATL in ATL-endemic areas (Kyushu and South Shikoku), were higher (RR greater than 2.0 and p less than 0.05) than those of controls in Kyushu, and lower (RR less than 0.5 and p less than 0.05) with respect to A24, Bw46, Bw52, Bw61 and DR7. The frequency of Bw52 was also lower in relatives positive for anti HTLV-I antibody than in relatives without antibody. However, these differences were not statistically significant after correction for the 45 antigens typed. These results can neither support nor refute the possibility of genetic susceptibility to HTLV-I infection and manifestation of ATL. PMID- 2895749 TI - Lymphoma-specific T- and B-cell responses suggest the involvement of HTLV-I in virus-non-productive lymphomas of a married couple. AB - In a married couple, a T-cell and a B-cell lymphoma occurred at the same time in the husband (FR) and wife (FE), respectively. Serum antibodies of patient FE with less advanced tumor progression specifically recognized HTLV-I-related envelope precursor molecules of 66-68 kDa molecular mass on HTLV-I-infected T- and B-cell lines, but not on HTLV-II or HIV-infected cells. In addition, in vivo activated CD8+ T-cell lines (TCL) from this patient specifically lysed autologous B-lymphoma cells, T-lymphoma cells from the husband (FR), as well as the HTLV-I transformed MT2 T-cell line. All positive target cells shared an HLA-class-I cross-reactive determinant identified by the alloantiserum WER127. On a clonal level, the specificity of the cytotoxic T-cell response was unequivocally distinguishable from classical natural-killer-like cytotoxicity. Results imply the involvement of a common inductive agent in the manifestation of malignant lymphoma in both patients (FR and FE). Since antibodies from cases with classical HTLV-I-induced adult T-cell leukemias (ATLL) did not bind antigens on cells of either lymphoma (FR or FE) and active virus production was not demonstrable under various different conditions, these results argue against HTLV 1 itself being the transforming agent. However, humoral and cellular immune responses of one patient (FE), in addition to de novo HLA-class-1 antigen expression of both patients, are nonetheless consistent with the involvement of viral infections(s). These were responsble for the expression of HTLV-1 characteristic envelope determinants of the malignant progeny of respective T- and B-cell origin. PMID- 2895750 TI - Expression of a hepatocyte membrane antigen during hepatocarcinogenesis and in the developing liver of the rat. AB - Changes in the expression of a cell membrane antigen during hepatocarcinogenesis and in the developing liver were analyzed by HAM.4, a monoclonal antibody (MAb) against a membrane glycoprotein of normal rat hepatocyte. Of the precancerous lesions observed during hepatocarcinogenesis induced by diethylnitrosamine, 2 acetylaminofluorene and partial hepatectomy, early neoplastic foci were uniformly stained by HAM.4. In contrast, some cells in the neoplastic nodules at the late stage did not express HAM.4 antigen on the cell surface. Of the cancer tissues, well-differentiated hepatocellular carcinomas were stained by HAM.4 whereas poorly differentiated carcinomas did not bind HAM.4 In developing rat liver, HAM.4 antigen was first expressed on fetal hepatocytes at the 18th day of gestation. It gradually increased until 4 weeks after birth when the intensity of the stain was almost the same as in adult rat liver. These results suggest that the expression of a membrane antigen defined by HAM.4 is closely associated with the differentiation of bile canalicular face and that HAM.4 might be useful in characterizing differentiation of cells during malignant transformation of hepatocytes. PMID- 2895751 TI - Prevalence of antibodies to 3 retroviruses in a captive colony of macaque monkeys. AB - The prevalence of antibodies to 3 retroviruses in the macaque colony of the New England Regional Primate Research Center (NERPRC) was determined using enzyme linked immunosorbent assay procedures as well as radioimmunoprecipitation-SDS polyacrylamide gel electrophoresis and indirect immunofluorescence tests. Out of 848 macaques, 3 (0.35%) had antibodies to simian immunodeficiency virus (SIV), 27 (3.2%) had antibodies to simian T-lymphotropic virus type I (STLV-1) and approximately 285 (34%) had antibodies to type D retrovirus. Of 3 macaques infected with SIV, 2 were rhesus monkeys (Macaca mulatta) and I was a cynomolgus monkey (Macaca fascicularis). STLV-1 and D retrovirus infection occurred in all 4 macaque species examined. SIV, STLV-1 and D retroviruses were isolated from sero positive macaques. The low prevalence of SIV infection suggests that SIV is not being readily transmitted among macaques at NERPRC; this contrasts markedly with the high SIV prevalence in some captive mangabey colonies. In contrast to African green monkeys from eastern Africa, 160 Caribbean green monkeys examined showed no sign of SIV infection. These results provide a framework for monitoring spontaneous disease associated with infection by these 3 retroviruses and will help in further definition of STLV-1 and SIV infection of non-human primates as animal models for human disease. PMID- 2895752 TI - Primary eye care in rural sub-Saharan Africa. AB - Primary eye care in rural sub-Saharan Africa is reviewed. In the context of eye care delivered by village health workers (VHW's) living in and supported by the community, such a system of health care does not exist in Africa today. There are no VHW's, and primary health care is currently a matter of experimentation and conjecture only. However, most basic eye care is rendered by non ophthalmologists; such care consists of screening, treatment of infections and inflammations, and in some cases, cataract surgery. Lower levels of non ophthalmic general health workers are being tasked to promote measures to prevent trachoma and xerophthalmia/nutritional blindness by intervention at the village level. Preliminary results of such programs are encouraging, and warrant further evaluation and expansion. PMID- 2895753 TI - Neurochemical perspectives of the narcoleptic syndrome. AB - Narcolepsy has been defined as a disorder of excessive sleep often associated with cataplexy, sleep paralysis and hypnagogic hallucinations. Although the pathophysiology of the narcoleptic syndrome is not well understood, derangement in the functions of CNS catecholamines and serotonin (5-HT) have been implicated. In the present paper we summarize evidence to suggest a role for the endogenous opioids in the regulation of normal sleep and in the pathophysiology of the narcoleptic syndrome. PMID- 2895754 TI - Isoproterenol stimulates aqueous flow in humans with Horner's syndrome. AB - Topical 1 percent isoproterenol in the presence of the phosphodiesterase inhibitor theophylline was tested for its ability to stimulate the rate of aqueous humor flow through the anterior chamber of the normal and the partially adrenergically denervated human eye (Horner's syndrome). Both the affected eye and the unaffected eye were observed to have lower flows at night than during the day. Isoproterenol had no significant effect on flow during the day in normal eyes or in Horner's syndrome, but during sleep this beta-adrenergic agonist increased flow in the normal eye by 34% and in the Horner's eye by 50%. We interpret the results as indicating that beta-adrenergic activity in the human eye can stimulate aqueous formation under some conditions. However, the observed stimulation could have been due to something other than increased beta-adrenergic activity in the ciliary epithelium. PMID- 2895755 TI - Acropustulosis of infancy--a case report. PMID- 2895756 TI - Homeotic genes, the homeobox, and the spatial organization of the embryo. PMID- 2895757 TI - A B-cell line having chromosome 14 aberration at break band q11 derived from an adult T-cell leukemia patient. AB - A B-cell line having translocations of chromosome 14 at break band q11 (the assigned locus of the alpha-chain gene of the T-cell antigen receptor) and chromosome 3 at break band p25 (the assigned locus of the c-raf-1 oncogene) was established from peripheral blood leukocytes of an adult T-cell leukemia (ATL) patient. The same chromosome 14 aberration at break band q11 and chromosome 3 aberration at break band p25 were also found in fresh T-cell leukemia cells. The B-cell line is surface immunoglobulin (sIg)+, immunoglobulin gene rearrangement+, ATL-specific antigen (ATLA)+, HTLV-1 proviral genome+, Epstein-Barr virus (EBV) associated nuclear antigen (EBNA)+ and the EBV DNA genome+. The fresh T-leukemic cells were T-cell receptor gene rearrangement+, the HTLV-1 proviral genome+ and EBV DNA genome. PMID- 2895758 TI - Spontaneous occurrence of placental glutathione S-transferase-positive foci in the livers of LEC rats. AB - Spontaneous occurrence of placental glutathione S-transferase (GST-P)-positive foci was observed in the livers of 5-month-old LEC rats. Quantitative studies revealed that GST-P foci appeared after the onset of hepatitis. The number and size of GST-P foci increased with age and more foci were induced in males than in females. No sex difference, however, was found in the incidence of hepatitis. Although hepatitis is necessary for the induction of GST-P foci, it is insufficient for their further growth. Since hereditary hepatitis first appears at around 4 months of age, leading to a high incidence of hepatocellular carcinomas in later life, the spontaneous occurrence of the foci may be related to the development of hepatocellular carcinoma. PMID- 2895759 TI - F-244 (1233A), a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A synthase: taxonomy of producing strain, fermentation, isolation and biological properties. PMID- 2895760 TI - Serum GGTP as a diagnostic aid in non-icteric chronic liver disease patients. PMID- 2895761 TI - Comparative amnestic effects of benzodiazepine hypnotic agents. AB - The effects of triazolam 0.5 mg and temazepam 30 mg on immediate and delayed recall in normal and insomniac subjects were evaluated in three separate, randomized, placebo-controlled, parallel group studies. Neither drug caused significant impairment of immediate recall. In the tests of delayed recall, triazolam caused a consistent anterograde amnestic effect. No significant impairment of delayed recall was observed in the temazepam study. Anterograde amnesia is thought to be a dose-related effect of benzodiazepines. Compounds with high benzodiazepine receptor affinity such as triazolam are thought to cause this type of amnesia more often than the lower-affinity compounds such as temazepam. PMID- 2895762 TI - Risk factors for drug-induced parkinsonism in tardive dyskinesia patients. AB - Using multivariate statistical analyses, the authors identified risk factors for development of drug-induced parkinsonism (DIP) in 66 tardive dyskinesia (TD) patients. Older age, recent use of neuroleptics, shorter duration of past neuroleptic exposure, and severity of TD were associated with increased risk of DIP. The clinician should devise treatment strategies in anticipation of the occurrence of DIP regardless of the presence or absence of TD, especially in older patients. New models for the pathophysiology of the two disorders are needed. PMID- 2895763 TI - Long-term outcome after neuroleptic malignant syndrome. AB - Little information is available on long-term outcome after neuroleptic malignant syndrome (NMS). Four patients are described who had survived episodes of NMS 2 to 11 years earlier. Some were safely re-treated with neuroleptics, and all safely received general anesthesia. No major sequelae were identified. Recommendations for management of patients after NMS are provided. PMID- 2895764 TI - An F1-ATPase beta-subunit precursor lacking an internal tetramer-forming domain is imported into mitochondria in the absence of ATP. AB - Post-translational import of the F1-ATPase beta-subunit precursor into isolated mitochondria requires both an energized inner membrane and nucleoside triphosphate hydrolysis on the organelle surface. Nested internal deletions of the F1 beta-precursor which progressively move a 128-residue carboxyl-terminal domain of the protein closer to the amino terminus reveal an abrupt transition between residues 122 and 144 to a form of the protein which is imported in the absence of added ATP. This transition region of the F1 beta-precursor is the same sequence which we have defined in earlier studies is required for formation of a tetramer following in vitro translation of the F1 beta-precursor. These data indicate that part of the requirement for ATP in the import of mitochondrial precursors may be involved in the reorganization of oligomeric species on the membrane surface which are formed following their translation. PMID- 2895765 TI - An immunogenic region within residues Val1670-Glu1684 of the factor VIII light chain induces antibodies which inhibit binding of factor VIII to von Willebrand factor. AB - We have identified a monoclonal anti-factor VIII (FVIII) antibody, C4, which inhibits the binding of purified human FVIII to purified human von Willebrand factor (vWF). Both whole immunoglobulin C4 and its Fab fragment demonstrated dose dependent inhibition of FVIII binding to vWF immobilized on the surface of polystyrene beads. Synthetic peptides based on the amino acid sequence of FVIII were tested for the ability to block the binding of C4 to FVIII in an enzyme linked immunosorbent assay system. A single synthetic FVIII pentadecapeptide, consisting of residues Val1670-Glu1684, was able to inhibit C4 binding to FVIII. Under the conditions used, the Val1670-Glu1684 peptide demonstrated total inhibition of C4 binding at a concentration of 1 microM. Synthetic FVIII peptides flanking and overlapping the Val1670-Glu1684 peptide had no significant inhibitory activity on C4 binding in concentrations up to 100 microM. A polyclonal antibody made to the Val1670-Glu1684 peptide also demonstrated inhibition of FVIII binding to vWF. Polyclonal antibodies made to synthetic FVIII peptides flanking and partially overlapping the Val1670-Glu1684 sequence did not demonstrate such inhibition. Localization of the binding region of the monoclonal anti-FVIII antibody C4 to residues Val1670-Glu1684 suggests that this site is at, or near, a major vWF binding domain of FVIII. PMID- 2895766 TI - Adenosine deaminase-complexing protein from bovine kidney. Isolation of two distinct subunits. AB - We have isolated a complex of two proteins from bovine kidney that bind to adenosine deaminase immobilized on Sepharose 4B. One protein, with Mr = 110,000, comigrates on both PAGE and SDS-PAGE gels with complexing protein isolated from rabbit kidney by the method of Schrader et al. (Schrader, W.P., Harder, C. M., and Schrader, D. K. (1983) Comp. Biochem. Physiol. B Comp. Biochem. 75, 119-126). The second protein has a Mr = 70,000. Both proteins bind to the adenosine deaminase-Sepharose but not to a control resin of bovine serum albumin bound to Sepharose. Based on a comparison of partial and complete denaturation on SDS-PAGE the two proteins appear to be bound to each other. At adenosine concentrations of 0.5-1 mM the isolated complexing protein increases small subunit adenosine deaminase catalytic activity by 20-30%. There may be some inhibition of catalytic activity at low adenosine concentrations. We have designated the 110,000 Mr protein CP-I, the 70,000 Mr protein CP-II and the complex of these two CP. PMID- 2895767 TI - Isolation and characterization of a receptor for type 1 fimbriae of Escherichia coli from guinea pig erythrocytes. AB - The adhesion of Escherichia coli to eukaryotic cells is mediated by proteinaceous surface appendages called fimbriae and complementary receptors on host cells. Although type 1 fimbriae, which contain a D-mannose-reactive lectin, have been well studied little is known about the binding mechanism of isolated fimbriae to individual cell receptors. This report describes the isolation and purification of a guinea pig erythrocyte receptor for type 1 fimbriae. Erythrocyte membranes were dissolved in 0.5% Triton X-100 and the receptor isolated and purified by affinity chromatography using type 1 fimbriae immobilized on Sepharose. The 65 kDa receptor, which inhibits the agglutination of guinea pig erythrocytes by type 1 fimbriated E. coli, has a pI of 8.5-8.7, and binds concanavalin A and type 1 fimbriae in a dose-dependent and saturable manner. The fimbrial binding activity of the receptor was reduced when treated with sodium metaperiodate, endoglycosidase H, trypsin, and V8 protease, suggesting the isolated receptor is a glycoprotein with N-linked carbohydrate units. Isolated type 1 fimbriae inhibited the binding of fimbriated E. coli to purified receptor in a dose- and time-related fashion. The calculated binding affinity was 6 X 10(6) M-1, a value consistent with the low binding affinity expected from previous studies of the agglutination of guinea pig erythrocytes by isolated type 1 fimbriae. PMID- 2895768 TI - Effect of an uncE ribosome-binding site mutation on the synthesis and assembly of the Escherichia coli proton-translocating ATPase. AB - Plasmid pRPG54, which carries the genes for the eight subunits of the proton translocating ATPase of Escherichia coli, has been found to carry a single base change of a G to an A in the ribosome-binding site for uncE, the gene which codes for the N,N'-dicyclohexylcarbodiimide-binding subunit c of the Fo. This noncoding region mutation both lowers expression of uncE by a factor of 2-3 and affects the function of the ATPase, specifically of the Fo sector. The presence of the mutation results in a decrease in the proton permeability of the Fo or of the entire F1Fo-ATPase complex when either is synthesized from genes on a multicopy plasmid. Expression of uncE from an F1Fo plasmid carrying the wild type ribosome binding site results in increased membrane proton permeability and decreased ability of the resultant ATPase to couple a transmembrane proton gradient to ATP synthesis both in vitro and in vivo. Also, although an Fo plasmid carrying the correct ribosome-binding site causes harmful, F1-dependent proton permeability in unc+ cells (Brusilow, W. S. S. (1987) J. Bacteriol. 169, 4984-4990), an identical plasmid carrying the mutation does not, even though it still codes for a functional reconstitutable Fo. The results show a relationship between the relative level of expression of uncE from a multicopy plasmid and the assembly pathway, proton permeability, and energy-coupling characteristics of the ATPase. PMID- 2895770 TI - Facilitation of Hb S polymerization by the substitution of Glu for Gln at beta 121. AB - In an effort to clarify the role of Glu-beta 121 of Hb S molecules in polymerization, we studied the solubility and kinetics of polymerization of various mixtures of deoxyhemoglobins S (Glu-beta 6----Val) and D Los Angeles (Glu beta 121----Gln). It is known that patients with Hb S-D Los Angeles have a relatively severe clinical course. Mixtures of Hb S and Hb D Los Angeles polymerized after a distinct delay time, the length of which depended on the initial hemoglobin concentration and the fraction of Hb S in the mixture. There was a linear relationship between the logarithmic plot of delay time and initial hemoglobin concentration. The line for a 1:1 mixture of Hb S and Hb D Los Angeles shifted to the right of that for deoxy-Hb S by 0.08. This shift is much smaller than the shift of 0.32 for 1:1 AS mixtures. From these data, the probability factor for nucleation of S-D Los Angeles hybrid hemoglobin was calculated to be 1.16, which is higher than that of Hb S (1.0) and AS hybrid hemoglobin (0.5). The degree of co-polymerization of Hb D Los Angeles in S-D Los Angeles mixtures was similar to that of Hb A in AS mixtures. The critical concentration for the polymerization of Hb D Los Angeles was between that of Hb A and Hb Machida, which has the same amino acid substitution (Glu----Gln) at the beta 6 position. These results suggest that the protein interaction of Hb S molecules during nucleation involves at least two steps. First, the Val-beta 6 of a Hb S molecule interacts hydrophobically with the Phe-beta 85 and the Leu-beta 88 of an adjacent Hb S molecule. In the second step, Glu-beta 121 weakens the interaction with His-beta 116 and Pro-alpha 114. The substitution of Glu-beta 121----Gln may strengthen this second reaction and facilitate nucleation as well as polymerization. PMID- 2895769 TI - Trinitrophenyl-ATP and -ADP bind to a single nucleotide site on isolated beta subunit of Escherichia coli F1-ATPase. In vitro assembly of F1-subunits requires occupancy of the nucleotide-binding site on beta-subunit by nucleoside triphosphate. AB - The stoichiometry of nucleotide binding to the isolated alpha- and beta-subunits of Escherichia coli F1-ATPase was investigated using two experimental techniques: (a) titration with fluorescent trinitrophenyl (TNP) derivatives of AMP, ADP, and ATP and (b) the centrifuge column procedure using the particular conditions of Khananshvili and Gromet-Elhanan (Khananshvili, D., and Gromet-Elhanan, Z. (1985) FEBS Lett. 178, 10-14). Both procedures showed that alpha-subunit contains one nucleotide-binding site, confirming previous work. TNP-ADP and TNP-ATP bound to a maximal level of 1 mol/mol beta-subunit, consistent with previous equilibrium dialysis studies which showed isolated beta-subunit bound 1 mol of ADP or ATP per mol (Issartel, J. P., and Vignais, P. V. (1984) Biochemistry 23, 6591-6595). However, binding of only approximately 0.1 mol of ATP or ADP per mol of beta subunit was detected using centrifuge columns. Our results are consistent with the conclusion that each of the alpha- and beta-subunits contains one nucleotide binding domain. Because the subunit stoichiometry is alpha 3 beta 3 gamma delta epsilon, this can account for the location of the six known nucleotide-binding sites in E. coli F1-ATPase. Studies of in vitro assembly of isolated alpha-, beta , and gamma- subunits into an active ATPase showed that ATP, GTP, and ITP all supported assembly, with half-maximal reconstitution of ATPase occurring at concentrations of 100-200 microM, whereas ADP, GDP, and IDP did not. Also TNP-ATP supported assembly and TNP-ADP did not. The results demonstrate that (a) the nucleotide-binding site on beta-subunit has to be filled for enzyme assembly to proceed, whereas occupancy of the alpha-subunit nucleotide-binding site is not required, and (b) that enzyme assembly requires nucleoside triphosphate. PMID- 2895771 TI - Arginine 328 of the beta-subunit of the mitochondrial ATPase in yeast is essential for protein stability. AB - The mitochondrial ATPase is rapidly inactivated by the arginine selective reagent phenylglyoxal. Recently, the purported major reacting residue has been reported for the chloroplast enzyme (Viale, A. M., and Vallejos, R. H. (1985) J. Biol. Chem. 260, 4958-4962) corresponding to Arg-328 in the beta-subunit of the yeast Saccharomyces cerevisiae mitochondrial ATPase, a highly conserved residue in the ATPase. This arginine residue was concluded to be in the active site of the ATPase and possibly involved in the binding of nucleotides. To test this hypothesis, site-directed mutagenesis of the yeast enzyme has been used to replace Arg-328 with alanine and lysine. The modified genes were transformed into a yeast strain, DMY111, which contained a null mutation in the gene coding for the beta-subunit of the ATPase. Both of the substitutions were functional in vivo as demonstrated by the ability of yeast transformants to grow on a nonfermentable carbon source. The water soluble F1-ATPase with Ala-328 and Lys-328 were extremely unstable, but could be stabilized with glycerol. The rate of enzymatic decay followed first order kinetics with half-lives of 1.1 and 4.0 min for the mutants with Ala-328 and Lys-328 in 10% and 5% glycerol, respectively, while the wild type enzyme was stable even in the absence of glycerol. Kinetic analysis of both ATPase and GTPase has been determined. The wild type enzyme had two observable apparent Km and Vmax values for ATPase which were 0.056 mM-1 and 67 units/min/mg and 0.140 mM-1 and 100 units/min/mg. The mutant enzyme containing Lys-328 showed similar kinetic values of 0.066 mM-1 and 23 units/min/mg and 0.300 mM-1 and 43 units/min/mg. The mutant enzyme containing Ala-328, however, only demonstrated a single site with values of 0.121 mM-1 and 45 units/min/mg. In contrast to ATPase activity, kinetic values for GTPase were nearly identical for the wild type and mutant enzymes. Opposite to predicted results, the mutant enzymes were more sensitive to the reagent phenylglyoxal. These results indicate that Arg-328 is important for protein stability, but not involved in catalysis. PMID- 2895772 TI - Pyridoxal 5'-diphospho-5'-adenosine binds at a single site on isolated alpha subunit from Escherichia coli F1-ATPase and specifically reacts with lysine 201. AB - Pyridoxal 5'-diphospho-5'-adenosine (PLP-AMP), an adenine nucleotide affinity analog, was found to bind in a saturable fashion to isolated alpha-subunit from Escherichia coli F1-ATPase with a stoichiometry of one mol/mol and a Kd approximately 150 microM. The binding was shown to be specific by the following criteria: 1) ATP reduced the binding of PLP-AMP by 80%, and 2) PLP-AMP, like ATP, induced a conformational change which increased the mobility of alpha-subunit in nondenaturing polyacrylamide gel electrophoresis and rendered alpha-subunit resistant to mild trypsin proteolysis. A stable adduct was formed between isolated alpha-subunit and [3H] PLP-AMP after reduction with NaBH4. alpha-Subunit labeled to the extent of 0.4-0.7 mol/mol was digested with trypsin and subjected to high pressure liquid chromatography purification, yielding a single labeled peptide. Automated amino acid sequencing showed that residue alpha-Lys-201 was specifically labeled. The results suggest that Lys-201 occupies a position proximate to the phosphate groups of bound ATP in the alpha.ATP complex. PLP-AMP did not support repolymerization of isolated alpha-, beta-, and gamma-subunits, consistent with previous reports that subunit repolymerization in vitro is dependent upon the presence of nucleoside triphosphate. Further, PLP-AMP-labeled alpha-subunit could not be reconstituted with isolated beta- and gamma-subunits in the presence of ATP, showing that occupation of the alpha-subunit nucleotide site by PLP-AMP impairs normal subunit-subunit interaction. PMID- 2895773 TI - Bovine adrenocortical cells exhibit high affinity transforming growth factor-beta receptors which are regulated by adrenocorticotropin. AB - Transforming growth factor beta (TGF-beta) at picomolar concentrations has been previously shown to induce striking alterations of bovine adrenocortical cell differentiated functions, without detectable effect on growth activity (Feige, J.J., Cochet, C., and Chambaz, E. M. (1986) Biochem. Biophys. Res. Commun. 139, 693-700; Hotta, M., and Baird, A. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 7795 7799). Adrenocortical cells in culture could bind 125I-labeled TGF-beta through at least two different binding systems. The highest affinity TGF-beta binding exhibited a Kd value of 5.7 X 10(-10) M and a calculated capacity of about 100,000 sites/cell, while the low affinity system yielded values of 4.3 X 10(-8) M and 2 X 10(6) sites/cell, respectively. The 125I-labeled TGF-beta bound to adrenocortical cells could be cross-linked using disuccinimidyl suberate and subsequent electrophoretic analysis revealed that TGF-beta was associated with two major cell components of about 280 kDa and 70-75 kDa, respectively, the latter one being resolved as a labeled doublet. Thus bovine adrenocortical cells exhibit a TGF-beta receptor similar to that defined by Massague and co-workers (Cheifetz, S., Like, B., and Massague, J. (1986) J. Biol. Chem. 261,9972-9978) in other cell types. Various growth factors, including fibroblast growth factor, as well as established hormonal activators of adrenocortical cell differentiated functions, such as angiotensin II and adrenocorticotropin, were examined as to their effect on TGF-beta receptor activity. A striking increase in the number of high affinity TGF-beta receptors was selectively elicited by ACTH in the nanomolar concentration range. This effect was time- and dose-dependent and was mimicked by cell treatment with dibutyryl cyclic AMP or forskolin. However, the ACTH-induced increase in receptor number was not impaired when protein synthesis was blocked. It is concluded that bovine adrenocortical cells are typical target cells for TGF-beta. This endocrine system represents a model in which, for the first time, the level of TGF-beta receptor is shown to be under hormonal regulation through a cyclic AMP-dependent pathway. PMID- 2895774 TI - Catalytic properties of chloroplast F1-ATPase modified at catalytic or noncatalytic sites by 2-azido adenine nucleotides. AB - When heat-activated F1-ATPase from chloroplasts was repeatedly exposed to Mg2+ and 2-azido-ATP, followed by separation from medium nucleotides and photolysis, a total of two sites per enzyme, both catalytic and noncatalytic, were labeled. In a coupled assay with pyruvate kinase about half the activity was lost when one site per enzyme was modified. However, increased modification resulted in no further loss of activity. In contrast, methanol-sulfite activation of the enzyme showed a loss of most of the catalytic capacity when one site per enzyme was modified. Predominant labeling of either one catalytic or one noncatalytic site caused a loss of most of the activity in either assay. An indication that the enzyme modified at one site retained some catalytic activity was verified by measurement of the [18O]Pi species formed when [gamma-18O]ATP was hydrolyzed by partially derivatized enzyme. With either catalytic or noncatalytic site modification, the distributions of [18O]Pi species formed showed that the modified enzyme had different catalytic characteristics. An interpretation is that with modification by azido nucleotides at either catalytic or noncatalytic sites, capacity for rapid catalysis is largely lost but the remaining sites retain weak modified catalytic properties. PMID- 2895777 TI - Arch marking technique for soldering intermaxillary hooks. PMID- 2895776 TI - Characterization of an outbreak of Clostridium perfringens food poisoning by quantitative fecal culture and fecal enterotoxin measurement. AB - Published criteria for implicating Clostridium perfringens as the cause of food poisoning outbreaks include finding a median fecal C. perfringens spore count of greater than 10(6)/g among specimens from ill persons. We investigated a food poisoning outbreak with the epidemiologic characteristics of C. perfringens related disease in a nursing home in which the median fecal spore count for ill patients (2.5 X 10(7)/g) was similar to that for well patients (4.0 X 10(6)/g), making the etiology of the outbreak uncertain. All ill and well patients tested had eaten turkey, the implicated food item. C. perfringens enterotoxin was detected by reverse passive latex agglutination in fecal specimens from six of six ill and none of four well patients who had eaten turkey (P = 0.005), suggesting that this organism had caused the outbreak. This investigation suggests that detection of fecal C. perfringens enterotoxin is a specific way to identify this organism as the causative agent in food-poisoning outbreaks. PMID- 2895775 TI - Comparison of complications during rehabilitation between conservative and early surgical management in thermal burns involving the feet of children and adolescents. AB - To evaluate the long-term sequelae of early surgical management compared with conservative therapy, a retrospective review from January 1976 to December 1984 was undertaken. Through inspection of burn diagrams, 395 patients were identified with burns involving the foot. From 1976 through 1980, 109 patients were managed in a conservative fashion with topical antimicrobial therapy and delayed debridement and grafting; 36 of these patients with severe burns were managed with skeletal suspension. Between 1981 and 1984, 136 patients were treated with earlier surgical debridement and grafting; during this period, skeletal suspension was rarely used. No statistical difference was found in mortality, amputations, incidence of open wounds, development of contractures, or number of patients requiring reconstructive procedures between conservative and early excision therapy except in those children treated with skeletal suspension. Thus in burns involving the feet in children, early excision and grafting does not alter the resultant morbidity compared with conservative burn management. PMID- 2895778 TI - Welding of TMA wire. Clinical applications. PMID- 2895779 TI - Distributions of tyrosine hydroxylase-, dopamine-beta-hydroxylase-, and phenylethanolamine-N-methyltransferase-immunoreactive neurons in the brain of the hamster (Mesocricetus auratus). AB - Antibodies to the catecholamine synthetic enzymes tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine-N-methyltransferase (PNMT) were used in an immunohistochemical analysis of the brain of the golden hamster. The distributions and morphological characteristics of neurons displaying immunoreactivity to these enzymes were examined in sets of adjacent sections. Various novel groups of TH-immunoreactive neurons were found. A distinct feature observed in the hamster brain was the presence of a population of magnocellular multipolar neurons in the basal forebrain which displayed intense TH immunoreactivity. These cells were found predominantly in the vertical and horizontal limbs of the nucleus of the diagonal band of Broca and in the lateral preoptic area. Many small TH-positive cells were also found scattered in the deeper layers of the cortex in the hamster. The pericentral divisions of the inferior colliculus contained a large number of TH-immunoreactive neurons, and a few small bipolar cells in the lateral superior olive were also stained. A major cell group was found in the lateral parabrachial nucleus at the level of the locus ceruleus that displayed TH but not DBH immunoreactivity and was obviously separate from the TH- and DBH-positive cells of the locus ceruleus. Additional TH positive cell groups were found along the seventh nerve, within the medial longitudinal fasiculus, in the nucleus raphe pallidus, and in the pars caudalis of the spinal trigeminal nucleus. The various catecholamine cell groups described by many people in the rat by use of histochemical and immunohistochemical techniques were also present in the hamster brain. These included the noradrenergic, TH- and DBH-immunoreactive cell groups of the pons and medulla. The hamster also displayed groups of medullary neurons displaying immunoreactivity to TH, DBH, and PNMT. These appeared similar in distribution and morphology to the adrenaline cell groups described in the rat. TH-immunoreactive cell groups in the olfactory bulb, hypothalamus, substantia nigra, and ventral tegmental area of the hamster appeared to correspond to the dopaminergic cells groups described in the rat and other species. In addition, as in the rat and cat, numerous TH-positive cells were found in the dorsal motor nucleus of the vagus, the nucleus of the solitary tract, and the area postrema. These observations suggest that catechols may be present in neurons in the cortex, basal forebrain, auditory brainstem, and the parabrachial nucleus of the hamster. These studies also emphasize the need for caution in making generalizations regarding transmitter distributions across species. PMID- 2895781 TI - Optometry in the neuropsychiatric hospital. PMID- 2895782 TI - Management of open-angle glaucoma. AB - Open-angle glaucoma is a non-curable, blinding disease which has its best prognosis when management begins at its earliest onset. Recent studies, such as those demonstrating axonal loss before functional or physical changes occur, will have an effect on the current standard of management. This includes indications for initiating treatment as well as what constitutes controlled intraocular pressure. Pharmacological management is often difficult due to drug tolerance and compliance problems. Some types of secondary open angle glaucomas respond very poorly to treatment. Hence, an accurate diagnosis is imperative to proper management. Principles underlying pharmacological management are discussed. When pharmacological management fails, laser and/or surgical intervention is required to prevent further vision loss. PMID- 2895780 TI - Selective dopamine-1 agonist therapy in severe hypertension: effects of intravenous fenoldopam. AB - To determine the effects of dopamine-1 agonist therapy in severe hypertension, blood pressure, heart rate, catecholamines and left ventricular function were studied in 18 patients (10 with renal disease) with diastolic blood pressure greater than 120 mm Hg (range 124 to 160) after intravenous fenoldopam therapy. Constant infusions of fenoldopam were titrated upward every 10 to 20 min from an initial dose of 0.1 microgram/kg per min to a maximal dose of 0.9 microgram/kg per min. The therapeutic goal of a supine diastolic blood pressure of less than 110 mm Hg was achieved in every patient within 1 h at an average dose of 0.34 +/- 0.22 microgram/kg per min. Blood pressure decreased from 214/134 +/- 33/10 mm Hg at baseline to 170/96 +/- 29/7 mm Hg (p less than 0.0001) at 3 h, whereas heart rate increased from 77 +/- 23 to 88 +/- 21 beats/min (p less than 0.01). Plasma norepinephrine increased during the fenoldopam infusion; epinephrine and dopamine levels did not change. Two indexes of left ventricular function (end-systolic dimension and isovolumic relaxation time) improved during the fenoldopam infusion, but mitral flow velocities during ventricular filling were unchanged. Side effects of intravenous fenoldopam were mild, transient and associated with the marked vasodilatory properties of the drug. Thus, fenoldopam is safe and effective as a parenteral monotherapy in patients with severe essential and renovascular hypertension. Preliminary data suggest that blood pressure reduction with selective dopamine-1 agonist therapy is accompanied by improved left ventricular function. PMID- 2895783 TI - Betaxolol and levobunolol: new beta-blocking antiglaucoma agents. AB - The Food and Drug Administration has recently approved the use of two new ophthalmic beta-adrenergic antagonistic agents: betaxolol hydrochloride (Betoptic) and levobunolol hydrochloride (Betagan). This paper reviews the history, pharmacologic properties, clinical efficacy and potential side effects of this expanding class of antiglaucoma medication. PMID- 2895784 TI - Comparative sensitivity of histo-pathology and specific lung parameters in the detection of lung injury. AB - The sensitivity of different parameters for the determination of lung injury caused by nitrogen dioxide (NO2) was investigated. Male rats were exposed to concentrations of 0, 4, 10 or 25 ppm NO2 for 6 h/day, for 7, 14 or 21 days. Histopathology of the nasal cavity, larynx, trachea and lungs was compared with the changes in macrophage function and morphology. In addition several biochemical parameters were determined in lung lavages. Cytotoxic effects were investigated in primary cultures of rat and bovine alveolar macrophages, exposed to the same NO2-levels as in the in vivo exposure. Treatment-related histopathological changes were observed in the lungs. No differences between exposed and control animals were observed in the nasal cavity, larynx or trachea. The morphology of the lavaged alveolar macrophages was changed at all exposure concentrations on day 7, 14 and 21. An increase in the number of macrophages was found after exposure to 10 and 25 ppm NO2 on days 7, 14 and 21. The phagocytic capacity was diminished after 14 and 21 days exposure to 25 ppm and at both times exposure to 10 and 25 ppm increased the level of gamma-glutamyl transferase (GGT) in lavage fluids. Morphology of the macrophages and levels of GGT were found to be sensitive parameters of nitrogen dioxide toxicity. In vitro exposure of rat and bovine alveolar macrophages to comparable NO2-concentrations induced effects on phagocytosis similar to those observed for macrophages from exposed rats. PMID- 2895785 TI - Antipsychotic drugs in schizophrenia: current issues. AB - In the 1950s antipsychotic antidopaminergic drugs were introduced as the pharmacological treatment of schizophrenia. In the last 35 years a large fund of knowledge has been acquired about these drugs. Still, a number of issues regarding them require further addressing. We have reviewed the literature on some of these issues, focusing on those factors that the previous studies have resolved inadequately. The issue of optimal dosages of antipsychotics in schizophrenia has been analyzed from the perspective of the dose requirements during "rapid tranquilization", "in acute psychotic phases of schizophrenia", "in chronically hospitalized psychotic schizophrenic patients" and during "maintenance phases of schizophrenia". We have briefly discussed the different methodologies available for measuring neuroleptic levels in plasma, their methodological weaknesses and strengths and some of the larger studies done with chlorpromazine, haloperidol and fluphenazine to establish correlations between levels, treatment response, oral dosages and side-effects. The theoretically fascinating concept of supersensitivity psychosis has been reviewed and the theoretical and practical weaknesses that exist in most of the papers that have claimed validity for this concept are presented. The article also reviews the preclinical, postmortem and clinical research that demonstrates the presence of site selectivity for dopamine receptors in the newer atypical neuroleptics. Finally, the article briefly reviews the current status of some unorthodox clinical strategies, that may be potentially applicable in managing schizophrenic disorders. PMID- 2895786 TI - Tolerance and rebound during and after short-term administration of quazepam, triazolam and placebo to healthy human volunteers. AB - Quazepam 15 mg, triazolam 0.25 mg and placebo were administered to 12 healthy volunteers. Each drug was given for 14 nights using a balanced design with at least 28 days between drug administrations. A test battery of physiological, psychological and subjective measures was administered on the mornings of days 1, 8, 14, 15 and 22 of the drug and post-drug periods. Seven days prior to and on days 1 to 28 of the drug and post-drug periods, sleep and self evaluation questionnaires were completed. Quazepam was associated with definite EEG effects, an unexpected improvement in simple motor performance and an increase in several bodily symptoms and ratings of sedation. Triazolam-impaired performance and also increased ratings of bodily symptoms and sedation. Two symptom increases with triazolam--metallic taste and touch sensitivity--might reflect day-time rebound. Sleep quality was improved by both drugs. There was little evidence of tolerance to drug effects on EEG or psychomotor tests. However tolerance was seen to the bodily symptoms and mood ratings. Rebound after drug discontinuation was not convincingly detected. PMID- 2895787 TI - Localization and phenotype of cycling and post-cycling murine thymocytes studied by simultaneous detection of bromodeoxyuridine and surface antigens. AB - Bromodeoxyuridine (BrdUrd) was incorporated in vivo or in vitro into the DNA of proliferating murine thymocytes. Surface antigens Thy1, Lyt2 (CD8), L3T4 (CD4), interleukin-2 receptor (IL2-R), and the V beta 8 chain of the T-cell receptor were detected using specific monoclonal antibodies with the biotin-avidin system, and cells were then treated for DNA denaturation. Simultaneous detection of BrdUrd and surface markers was performed on cell smears and frozen sections by double-color immunofluorescence. The phenotype of cycling cells, determined in fetal thymus and in the thymus of mice from birth to one year of age, showed relative stability after the initial growth period, despite severe involution of the gland. Phenotypic evolution of cycling cells and their progeny was also studied in colchicine-treated animals and was shown to reproduce sequential events of T-cell differentiation. On sections, the highest frequency of cycling cells was observed in the outer cortex in normal thymus, but the first cells to start proliferation during regeneration were mostly located in the deep cortex and corticomedullary junction. These results show the high potential of this method, as compared to autoradiography of radiolabeled cells. PMID- 2895788 TI - Characterization of monoclonal antibodies specific for rabbit renal brush-border hydrolases: application to immunohistological localization. AB - By use of immunodepletion studies, we characterized four monoclonal antibodies reactive with rabbit brush-border (BB) as specific for aminopeptidase N (AP), dipeptidylpeptidase IV (DPPIV), neutral endopeptidase (EP), and angiotensin converting enzyme (ACE), and we used these antibodies for immunohistochemical detection of these four hydrolases. Expression within the kidney was studied by light and electron microscopy. All four hydrolases are expressed on the various segments of the proximal tubule. In addition, EP and DPPIV are detectable on visceral epithelial cells of the glomerulus and AP on the cells of Bowman's capsule. Outside the kidney, the four hydrolases are expressed within the digestive and genital tracts, where AP, EP, and DPPIV predominate on epithelial structures, whereas ACE is essentially located in vascular structures. The latter localization is also characteristic of ACE in the other organs studied, where clear-cut systematic distribution of the other hydrolases was often difficult to demonstrate. In addition, AP, DPPIV, and EP were detected on lymphoid cells. As compared to reports of data obtained essentially by enzymatic or immunoradiometric assays, these observations suggest considerable interspecies variations of extrarenal expression of the major BB hydrolases. This should be taken into account in attempting to define a general physiological role for a given enzyme. PMID- 2895789 TI - Thy-1- and Ly-6-mediated lymphokine production and growth inhibition of a T cell hybridoma require co-expression of the T cell antigen receptor complex. AB - Repetitive subcloning of an Ag-specific T cell hybridoma yielded a variant that lacked functional mRNA for the Ag receptor (Ti, T cell Ag receptor alpha/beta heterodimer) beta-chains and failed to express CD3/Ti on the cell surface. Transfection with the original Ti alpha- and beta-chain genes restored CD3/Ti expression to normal levels. Whereas the parental T cell hybridoma produced IL-2 when stimulated with mAb against CD3, Thy-1, and Ly-6, the CD3/Ti negative cell failed to do so. Reconstitution of CD3/Ti expression restored normal IL-2 production in response to these mAb. A separate response to activation, the inhibition of transformed growth, was also dependent upon co-expression of CD3/Ti. These data demonstrate that cell surface expression of CD3/Ti is required for IL-2 production and growth inhibition initiated by two distinct activating molecules, and suggest that CD3/Ti may be a final common pathway for many transmembrane activation signals. PMID- 2895790 TI - Development of a human monoclonal antibody from a Graves' disease patient that identifies a novel thyroid membrane antigen. AB - To investigate the interaction between antibodies and the thyroid gland in Graves' disease, PBL were harvested from seven Graves' disease patients and transformed into lymphoblasts by the addition of EBV in the presence of cyclosporine A. These lymphoblasts were cloned by limiting dilution and then assayed for binding activity to human thyroglobulin, thyroid-stimulating hormone, thyroid microsome, and thyroid as well as guinea pig fat cell membranes. Four patients' cells produced antibody that bound to at least one of the Ag; a single clone from one patient that bound equally well to both thyroid and guinea pig fat cell membranes (but not to other thyroid Ag) was selected for further evaluation. Fusion of these cells with SHM-D33 heteromyeloma cells yielded three cell lines that produced genetically identical mAb. Immunostaining of human thyrocytes with this mAb demonstrated an Ag present on both nuclear and cell membranes. This Ag was identified as an 18,000 m.w. protein band on Western blots of both human thyroid and guinea pig fat cell membranes. The mAb was also able to alter thyrocyte physiology as the short term incubation of this mAb with FRTL-5 cells in vitro inhibited thyroid-stimulating hormone-mediated production of cAMP. Thus, this mAb and the Ag it identifies may be relevant to Graves' disease. PMID- 2895791 TI - IL-2 receptor(p55)/Tac-inducing factor. Purification and characterization of adult T cell leukemia-derived factor. AB - Many human T cell lymphotropic virus-I (HTLV-I) transformed T cells from adult T cell leukemia (ATL) patients continuously produce a humoral factor called ATL derived factor (ADF) which induces IL-2R/Tac expression on T and NK cells. Using gel filtration, procion red Sepharose, DEAE, and reverse phase chromatography, we have purified ADF protein to homogeneity from 15 liters of serum-free culture supernatant of an HTLV-I(+) T cell line ATL-2. Purified ADF protein had the m.w. of 14,000 by SDS-PAGE and gel filtration, and its isoelectric point is around 5.0. ADF did not react with heteroantibodies against IL-1 alpha and IL-1 beta, which have also IL-2R/Tac-inducing activity on suitable target cells. Partial N terminal amino acid sequence of ADF is different from other cytokines such as, IFN, BSF-2, and various IL whose cDNA has been cloned. Western blot analysis using rabbit antibodies against N-terminal 10mer synthetic peptide of ADF showed that IL-1 alpha and ADF are different proteins. ADF had its IL-2R/Tac-inducing activity not only on human NK-like cell line YT, but also on HTLV-I(+) T cells, such as ED. In contrast, macrophage-derived IL-1 lacked IL-2R/Tac-inducing activity on ED cells despite their IL-2R/Tac induction on YT, indicating that ADF and IL-1 have their effect via different receptors. PMID- 2895792 TI - Stimulation of guanylate cyclase activity and reduction of adenylate cyclase activity by granulocyte-macrophage colony-stimulating factor in human blood neutrophils. AB - Human neutrophils were incubated with granulocyte-macrophage (GM)-CSF and examined for changes in second messenger systems. Twofold increases in cGMP but not cAMP were measured after 5 to 20 min with 100 U/ml GM-CSF. Guanylate cyclase activities in membrane and cytosol fractions were increased to the same extent whether measured in the presence of Mg2+ or Mn2+, or in the cytosol with Mg2+ + N methyl-N'-nitro-N-nitroso-guanidine. Kinetic studies of the cytosol enzyme showed no changes in the Km values for Mg2+ and Mn2+dependent guanylate cyclase activities (0.91 and 0.022 mM, respectively), whereas Vm values were increased after treating intact cells with GM-CSF. Two peaks of guanylate cyclase activity were observed, one at 10 and another at 60 min after adding 100 U/ml GM-CSF, whereas only one peak at 5 min occurred with 1 U/ml. Adenylate cyclase activity was reduced by nearly 50% after adding 100 U/ml GM-CSF for 10 to 30 min. These effects were also seen in the presence of several hormonal and nonhormonal adenylate cyclase stimulators. In contrast, small increases in adenylate cyclase activity occurred after adding 1 U/ml GM-CSF. In experiments to examine the pathway of guanylate cyclase activation by GM-CSF, we observed no changes in inositol phosphates, intracellular calcium ion, or cytosolic protein kinase C. The augmentation of chemotactic peptide-induced superoxide production by GM-CSF concentrations, may be related to the effects of the higher levels of GM-CSF to stimulate late increases in guanylate cyclase or decreases in adenylate cyclase. PMID- 2895793 TI - Relation between arachidonic acid metabolism and development of thymocytes in fetal thymic organ cultures. AB - Because products of arachidonic acid metabolism, particularly the PG, have been implicated as modulators of growth and differentiation of adult thymocytes, we investigated relations between metabolism of arachidonic acid and growth, as well as differentiation, of thymocytes during fetal thymic organ culture. Fetal thymic cells synthesized immunoreactive PGE2 during organ culture and were found to be capable of metabolizing exogenous arachidonic acid to products that cochromatographed with authentic 6-keto-PGF1 alpha, PGE2, PGF2 alpha. Synthesis of these products and growth and expression of Thy-1 and Lyt-1 Ag were inhibited by culture of fetal thymic lobes with indomethacin, a cyclooxygenase inhibitor, as well as meclofenamate and eicosatetraynoic acid, inhibitors of cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism. Only indomethacin inhibited expression of Lyt-2. Culture with eicosatetraynoic acid also inhibited the capacity of thymic lobes to synthesize 15-hydroxyeicosatetraenoic acid-like products. The inhibitory effects of indomethacin on growth and expression of Thy 1 were partially reversed by simultaneous addition of arachidonic acid. Thus, fetal thymic cells appear to require an intact cyclooxygenase, and possibly lipoxygenase, pathway of arachidonic acid metabolism for growth and differentiation. These data also provide evidence that Lyt-1 and Lyt-2 may be regulated by different requirements with respect to arachidonic acid metabolism. PMID- 2895794 TI - Stable T3- and T3+ subclones derived from the mosaic human T cell leukemia cell line, CEM. AB - An unexplained feature of the human T lymphoblastic leukemia cell line, CEM, is a heterogeneous expression of surface membrane T3-TCR complex. CEM cells constitutively maintain two distinct populations whereby a minority of cells (5 to 16%) express T3 but the remainder do not. From the parental cell line, we have derived stable subclones in which all cells express surface T3 and companion subclones that lack surface T3. Inasmuch as surface T3 expression is contingent on assembly and coexpression of the multichain T3 protein complex with the TCR, we compared the surface T3+ and T3- subclones for their rearrangement and expression of genes of the T3-TCR complex. Restricted DNA of both subclone types showed the identical monoclonal pattern of TCR gene rearrangement seen in the mosaic parental CEM line. Northern blot analysis revealed mRNA transcripts of TCR beta subunit and T3 delta in both the surface T3+ and T3- subclones. However, surface T3+ subclones transcribed abundant full length (1.5-kb) TCR alpha mRNA in contrast to the surface T3- subclones in which TCR alpha transcripts were undetectable. Lack of TCR alpha gene transcription was not attributable to either unrearranged or aberrantly rearranged TCR alpha genes because exposure of surface T3- cells to phorbol ester induced a rapid (15-min) and progressive accumulation of full length (1.5-kb) TCR alpha mRNA. This was followed by surface membrane T3 expression in 24 to 72 h. We conclude that the unusual phenotypic mosaicism of CEM cells is attributable to a reversible lack of transcription of the TCR alpha gene. PMID- 2895795 TI - Monoclonal antibodies to proliferating cell nuclear antigen (PCNA)/cyclin as probes for proliferating cells by immunofluorescence microscopy and flow cytometry. AB - Proliferating cell nuclear antigen (PCNA)/cyclin is an intranuclear polypeptide antigen that is found in both normal and transformed proliferating cells. We have recently described two mouse monoclonal antibodies reacting with PCNA. In this report we describe the application of these antibodies to the study of proliferating human cells by indirect immunofluorescence microscopy and by flow cytometry. A fixation/permeation procedure was developed in order to obtain satisfactory binding of monoclonal PCNA-specific antibodies to proliferating cells. This method involved fixation with 1% paraformaldehyde followed by methanol treatment. For the staining of cells in suspension with the IgM type monoclonal antibodies lysolecithin was added to the paraformaldehyde solution to achieve a better permeation by the antibody molecules. This procedure gave a good ratio of specific staining relative to the background staining. It also preserved the shape and normal architecture of the cells as judged by visual microscopic observation and by light scatter measurements using a flow cytometer. Furthermore, this fixation technique permits simultaneous labeling of DNA by propidium iodide and PCNA by monoclonal antibodies. PCNA was detected in various types of normal and transformed proliferating cells by indirect immunofluorescence. Quiescent peripheral blood mononuclear cells were PCNA negative whereas a fraction of lectin-stimulated lymphocytes became PCNA positive. Similarly, early passages of fetal skin fibroblasts were PCNA-positive but non-proliferating senescent fibroblasts of later passages were PCNA-negative. The association of PCNA-staining by monoclonal antibodies with cell proliferation was confirmed by flow cytometry. Simultaneous labeling of PCNA and DNA showed that the PCNA signal increased during the G1 phase of the cell cycle, reached its maximum in the S-phase, and declined during the G2/M phase. Using cell sorting we demonstrated that mitotic cells had a very low PCNA signal. Thus, monoclonal PCNA specific antibodies offer a convenient tool for the detection of human cell proliferation by immunofluorescence microscopy and by flow cytometry. PMID- 2895796 TI - ApoB gene MspI RFLP in exon 26 changes amino acid 3611 from Arg to Gln. AB - An apolipoprotein B gene MspI RFLP was identified by the use of a probe to a portion of the 3' end of the gene. By Southern blotting analysis after digestion with MspI, this probe detected either a 9 kb or a 2.6 kb fragment. Family studies showed that these corresponded to alleles that segregated in a simple Mendelian fashion. The minor allele (9.0 kb) had a frequency of approximately 12% in an unrelated Caucasian population. Restriction mapping showed that the minor allele was due to the loss of an MspI site in exon 26. Sequencing of both alleles in the region containing the polymorphic MspI site revealed a single-base pair alteration which abolished the MspI site at codon 3611 of the mature apoB protein. In the major allele, this codon is CGG, which specifies Arg; whereas in the minor allele, it was CAG, which codes for Gln. PMID- 2895797 TI - Characterization of immunoreactive dynorphin in human phaeochromocytomas. AB - The prodynorphin-derived opioids, dynorphin (DYN) and alpha-neoendorphin (alpha NE) were studied in 24 human phaeochromocytomas and related tumours. Nineteen tumours, extracted in HCl (0.1 mol/l), contained concentrations of immunoreactive DYN (ir-DYN) ranging from less than 0.5 to 794 pmol/g wet weight. None of the extracts in HCl contained ir-alpha NE (all less than 2.4 pmol/g). Sephadex G-50 gel filtration chromatography of ir-DYN in HCl (0.1 mol/l) extracts of six tumours revealed three small peaks of ir-DYN of higher molecular size (approximately 12,000, 6000 and 3000 daltons), a minor peak of ir-DYN eluting just after DYN(1-17), and a broad major peak, consisting of at least three components, which was significantly retarded and eluted after the salt volume of the column. High-pressure liquid chromatography (HPLC) of these extracts revealed multiple peaks of ir-DYN, most of which did not coelute with any synthetic DYN peptides. On both gel filtration chromatography and HPLC, one of the minor peaks coeluted with DYN(1-32). None of the peaks of ir-DYN coeluted with DYN(1-17) which had been acetylated using acetic anhydride. Extracts of the same tumours in acetic acid (0.1 mol/l) yielded similar values for ir-DYN content, but parallelism in the assay was improved. Sephadex G-50 chromatography revealed a different pattern of ir-DYN with a major peak coeluting with DYN(1-17) and, in two tumours, a minor peak coeluting with DYN(1-8). Studies with HPLC revealed, however, that substantial degradation of synthetic DYN occurred during extraction in acetic acid (0.1 mol/l) in spite of the precautions taken. Phaeochromocytomas frequently contain ir-DYN in concentrations which may approach that of the mammalian pituitary. These tumours did not, however, contain ir-alpha NE and, with the possible exception of a small amount of DYN(1-32), the ir-DYN present did not correspond with any known sequences. Thus, whilst prodynorphin is expressed in phaeochromocytomas, it does not seem to be processed to the usual end-products, and post-translational modifications therefore seem likely. Enzymatic degradation of DYN may occur during extraction in acetic acid (0.1 mol/l), and this medium should, therefore, be avoided in studies of such labile peptides. PMID- 2895798 TI - A comparison of the adhesion, coaggregation and cell-surface hydrophobicity properties of fibrillar and fimbriate strains of Streptococcus salivarius. AB - Fibrillar and fimbriate strains of Streptococcus salivarius were compared for their ability to adhere to buccal epithelial cells and saliva-coated hydroxyapatite beads, and for their ability to coaggregate with Veillonella strains. The fibrillar Lancefield group K strains adhered statistically significantly better to both buccal epithelial cells and saliva-coated hydroxyapatite beads than the fimbriate strains, which lacked the Lancefield group K antigen. After 1 h the fibrillar strains coaggregated statistically significantly better than the fimbriate strains with V. parvula strain V1, but after 24 h, coaggregation both of fibrillar and of fimbriate strains reached approximately 90%. Freshly isolated Veillonella strains all coaggregated with the S. salivarius strains, but the percentage coaggregation varied considerably after 1 h depending on the Veillonella strain. Coaggregation was independent of the presence of Ca2+. S. salivarius strain HB-V5, a mutant of strain HB that had lost the Veillonella-binding protein, coaggregated weakly with V. parvula strain V1, but coaggregated very well with other wild-type veillonellae, suggesting the presence of an alternative mechanism for Veillonella-binding for strain HB. Fibrillar strains were, therefore, more adhesive to oral surfaces and coaggregated with veillonellae after 1 h better than the fimbriate S. salivarius strains. Both fibrillar and fimbriate strains were highly hydrophobic in the hexadecane-buffer partition assay. PMID- 2895799 TI - Baculovirus expression of the small genome segment of Hantaan virus and potential use of the expressed nucleocapsid protein as a diagnostic antigen. AB - Autographa californica nuclear polyhedrosis virus (AcNPV) was used as an expression vector for the nucleocapsid protein gene of Hantaan virus. Two different cDNA clones representing the small genome segment of Hantaan virus were inserted into the transfer vector pAcYM1, and recombinants were generated by replacement of a portion of the baculovirus polyhedrin gene with the foreign, Hantaan virus gene. Recombinants containing both the first and second ATG initiation codons of the Hantaan virus gene produced nucleocapsid protein, while those containing only the second codon did not. The expressed nucleocapsid protein was evaluated as a potential diagnostic antigen with a variety of hantavirus-immune sera. The high levels of expression obtained, specific serological reactivity with immune sera and the low level of biological containment required for production of this protein all suggest a significant advantage over authentic viral antigen for diagnosis of hantavirus infection. PMID- 2895800 TI - Western blot detection of scrapie-associated fibril protein in tissues outside the central nervous system from preclinical scrapie-infected mice. AB - We describe a method of sample preparation to detect scrapie-associated fibril (SAF) proteins in small amounts of scrapie-infected mouse tissues by Western blot analysis using an antiserum to a synthetic peptide that corresponds to the N terminal region of hamster prion protein. SAF proteins were efficiently detected in brain tissue by this procedure. The proteins were also detected in preparations from spleen and lymph node. SAF proteins were detected in brain samples at 24 weeks after intraperitoneal infection. Using spleen samples, the proteins were detected from mice in the preclinical stage (from 4 weeks after infection), clinical symptoms of scrapie were observed in some mice from 22 weeks after infection. PMID- 2895801 TI - A prospective randomized phase III trial comparing combination chemotherapy with cyclophosphamide, fluorouracil, and either doxorubicin or epirubicin. French Epirubicin Study Group. AB - Two hundred sixty-three patients with advanced breast cancer were randomized to two treatment regimens consisting of fluorouracil, 500 mg/m2; cyclophosphamide, 500 mg/m2; and either epirubicin (Farmorubicin, Farmitalia Carlo Erba SpA, Italy), 50 mg/m2 (FEC); or doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH), 50 mg/m2 (FAC), administered intravenously (IV) every 3 weeks. Two hundred thirty patients (FAC, 113; FEC, 117) were evaluable for response, and 244 patients for toxicity (FAC, 120; FEC, 124). The two groups were comparable with respect to age, menopausal status, disease-free interval to first recurrence, time from initial diagnosis to protocol activation, indicator lesions, performance status, and prior adjuvant therapy. Of 117 evaluable patients treated with FEC, 59 (50.4%) had a partial response (PR) or complete response (CR), 40 showed no change (NC), and 18 had progressive disease. Of 113 evaluable patients treated with FAC, 54 (52%) showed a remission, 30 NC, and 18 progression. There was no statistical difference between the two regimens in overall response rate, response rate according to tumor site, time to response, or duration of response. Median survival was 15 months for FEC and 18.2 months for FAC (not significant). In the 120 patients evaluable for toxicity treated with FAC, three episodes of congestive heart failure (CHF) were observed after 225, 350, and 550 mg/m2 of doxorubicin, respectively. Of the 124 evaluable patients treated with FEC, 25 received greater than 600 mg/m2 of epirubicin and no CHF was recorded. FEC induced significantly less neutropenia (P = .01), less nausea and vomiting (P less than .01), and less complete alopecia (P less than 10(-3) than did FAC. The results of this study demonstrate that FEC is as effective a regimen as FAC for the therapy of advanced breast cancer. Moreover, FEC was better tolerated than FAC in this patient population. PMID- 2895802 TI - Unmyelinated cutaneous afferent neurons activate two types of excitatory amino acid receptor in the spinal cord of Xenopus laevis embryos. AB - The trunk and tail skin of Xenopus laevis embryos near the time of hatching is innervated by the mechanoreceptive free nerve endings of Rohon-Beard neurons, a homogeneous class of cutaneous primary afferent fibers. Rohon-Beard neurons have cell bodies and axons in the dorsal spinal cord, where they monosynaptically excite a population of dorsolaterally situated interneurons (Clarke and Roberts, 1984). EPSPs can be recorded in these dorsolateral interneurons following electrical stimulation of the unmyelinated neurites of Rohon-Beard neurons in the skin. The EPSPs are dual component, consisting of separate fast and slow potentials that are usually evoked synchronously and that closely resemble those described previously in Xenopus and lamprey motoneurons (Dale and Roberts, 1985; Dale and Grillner, 1986). The excitation of dorsolateral interneurons by Rohon Beard neurons is reduced by the bath application of excitatory amino acid antagonists. Kynurenic acid suppresses both the fast and slow components of the EPSPs, while both (+/-)-2-amino-5-phosphonovaleric acid (APV) and 1 mM magnesium reduce the slow component but have little or no effect on the peak amplitude of the EPSPs. These data suggest that Rohon-Beard neurons release an excitatory amino acid neurotransmitter, which acts simultaneously at both N-methyl-D aspartate (NMDA) and non-NMDA receptor types. This is the first direct demonstration of dual-component excitatory amino acid-mediated synaptic transmission from cutaneous primary afferent neurons in the vertebrate spinal cord. The bath application of the agonists NMDA, kainate, or quisqualate in salines containing 1 microM TTX depolarized the interneurons and reduced their input resistance, which suggests that the interneurons possess all 3 types of excitatory amino acid receptor. Kynurenic acid strongly inhibits responses to NMDA and kainate, but is relatively less effective against the larger responses of quisqualate in this system. PMID- 2895803 TI - Effect of removal of the endothelium on vasocontraction in canine and rabbit basilar arteries. AB - The effect of endothelium removal on the contractile responses to KCl, hemoglobin, serotonin (5-HT), norepinephrine (NE), prostaglandin (PG)F2 alpha, PGD2, and PGE2 was investigated in canine and rabbit basilar arteries by an isometric tension-recording method. In canine basilar arteries, endothelium removal elevated the dose-response curves to 5-HT, PGF2 alpha, and PGD2, and PGE2, but not to KCl, hemoglobin, or NE. In rabbit basilar arteries, on the other hand, removal of the endothelium elevated the dose-response curves to 5-HT, NE, PGF2 alpha, and PGD2, but not to KCl or hemoglobin. Neither contractile nor inhibitory response was elicited by PGE2 in rabbit basilar arteries. Contraction induced by 5-HT and NE following endothelium removal had a much more pronounced effect in rabbit basilar arteries than in canine basilar arteries. These results suggest that, following endothelium removal, abolition of the spontaneous release of endothelium-derived relaxing factor is the most probable mechanism of the enhanced vasocontraction. Since endothelial damage results from subarachnoid hemorrhage, the aforementioned mechanism of vasocontraction enhancement may play a role in the pathogenesis of cerebral vasospasm. PMID- 2895804 TI - Dietary linolenic acid and longer-chain n-3 fatty acids: comparison of effects on arachidonic acid metabolism in rats. AB - Rats were fed graded amounts of purified 18:3n-3 or fish oil concentrate in the presence of a constant amount of 18:2n-6 to evaluate the ability of 18:3n-3 compared with longer-chain n-3 fatty acids to inhibit 20:4n-6 metabolism in platelets and lungs. Dietary 18:3n-3 at a ratio of 0.28 (n-3 to n-6 fatty acids) suppressed levels of 20:4n-6 in lung and plasma phospholipids and the capacity of the tissues to synthesize cyclooxygenase-derived products in a dose-dependent fashion. At similar ratios of n-3 to n-6 dietary fatty acids, longer-chain n-3 fatty acids, which are abundant in fish oil, appear to be more effective than 18:3n-3 in suppressing 20:4n-6 levels and the capacity of the tissues to synthesize cyclooxygenase-derived products. Much greater amounts of 12 hydroxyeicosapentaenoic acid (12-HEPE) and 5-HEPE than of 12 hydroxyeicosatetraenoic acid (12-HETE) and 5-HETE appeared to be formed in tissues of the group receiving the highest amount of fish oil. These results suggest that ingestion of fish oil leads to increased formation of lipoxygenase derived products of longer-chain n-3 fatty acids. PMID- 2895805 TI - Cryptorchidism in spina bifida and spinal cord transection: a clue to the mechanism of transinguinal descent of the testis. AB - In spina bifida there is a high incidence of cryptorchidism, particularly where the lesion is at or above L2. This article describes the location of the testis in 32 spina bifida patients and the effect of spinal cord transection in neonatal rats: both studies suggest that the spinal cord influences testicular descent. It is already established that androgens, an intact genitofemoral nerve, and the gubernaculum are essential for the transinguinal phase of testicular descent to occur. Yet the mechanism by which testosterone exerts its effect on the gubernaculum remains obscure. To account for all the observed phenomena we postulate that a spinal cord nucleus may exist that is sensitive to androgens and mediates impulses through the genitofemoral nerve to the gubernaculum. Neuronal modulation of the gubernaculum may induce testicular descent. PMID- 2895806 TI - Synthesis of certain 3-[4-[2-hydroxy-3-(isopropylamino) propoxy]phenyl]propionate as beta-adrenergic blocking agents. PMID- 2895807 TI - [Drug reactions and interactions]. PMID- 2895808 TI - The excitatory effect of the new histamine H2-receptor antagonist nizatidine (LY 139037) on the guinea pig ileum. AB - The histamine H2-receptor antagonist, nizatidine (LY 139037), was tested for its effect on the intestinal smooth muscle. Isolated segments of guinea pig ileum were used in Tyrode solution at 37 degrees C. Nizatidine (from 3.2 X 10(-6) to 3.2 X 10(-4) M) caused a concentration-dependent contractile response by the guinea pig ileum. The average maximum response to nizatidine (3.2 X 10(-4) M) was about 89% of the average maximum response to eserine (3.2 X 10(-6) M). The contractile responses induced by nizatidine were not modified by pyrilamine (10( 8) and 10(-7) M). On the other hand, atropine (10(-8) and 3.2 X 10(-8) M) significantly prevented, while eserine (10(-8) and 3.2 X 10(-8) M) significantly enhanced the nizatidine-induced responses in a concentration-dependent manner. These findings suggest that nizatidine exerts an excitatory effect on the guinea pig ileum which seems to be associated with the cholinergic system, probably through a direct and/or an indirect mechanism (inhibition of acetylcholinesterase and/or increased release of acetylcholine). PMID- 2895809 TI - Reserpine, vagal adrenergic activity and stress-induced acute gastric mucosal injury in the rat. AB - 1. Stress activates the hypothalamus causing central adrenergic discharge and stimulation of the autonomic sympathetic system. Reserpine produces the same effect and, therefore, its acute gastric mucosal injury is stress-induced. This injury was employed in the gastric diversion rat, a model for determining gastric acid secretion under basal conditions, to examine the relationship of the vagus nerve to the autonomic sympathetic system in the mechanism of stress-induced acute gastric mucosal injury. 2. After 6 h of reserpine (5 mg/kg I.P.), all rats developed oval or round lesions confined to the glandular stomach and of no constant relationship to rugal crests (lesion score 29 +/- 2.7 mm2, mean +/- S.E., n = 10). Microscopically, these lesions were vascular in origin, developing as intramural foci of haemorrhage or necrosis and expanding to communicate with the lumen. Pre-treatment with potent antisecretory doses of the anticholinergic atropine (5 mg/kg I.P.) or the H2-receptor antagonist cimetidine (40 mg/kg I.P.) did not influence this reserpine action (28 +/- 3 mm2 and 27.5 +/- 2.3 mm2, respectively, mean +/- S.E., n = 10). Protection against the reserpine lesions by the alpha-adrenoceptor blocking drugs phenoxybenzamine or phentolamine given in a dose of 10 mg/kg I.P. was significantly (P less than 0.01) more than that afforded by the 5 mg/kg I.P. dose. However, the 15 mg/kg I.P. dose was completely protective against the lesions. Vagotomy had a similar protective effect. Interruption of autonomic sympathetic delivery to the stomach by coeliac ganglionectomy had no influence on the macroscopic or microscopic effects of reserpine on the stomach (30.5 +/- 3.4 mm2, mean +/- S.E., n = 10). 3. The H+ output associated with 6 h of gastric diversion (61 +/- 4.5 mumol, mean +/- S.E.) was significantly (P less than 0.001) depressed by reserpine alone (26 +/- 2 mumol) or with atropine (19 +/- 1.8 mumol) or cimetidine (21 +/- 2 mumol). Protection against the reserpine lesions by phenoxybenzamine or phentolamine was associated with dose-dependent increase of H+ output, which with the 15 mg/kg dose was similar to that of control values (58 +/- 4.1 mumol and 60.3 +/- 2.8 mumol vs. 61 +/- 4.5 mumol). Vagotomy protection was associated with an H+ output significantly (P less than 0.001) lower than that with reserpine alone (14 +/- 1.4 mumol). Coeliac ganglionectomy had no influence on the H+ output associated with reserpine treatment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2895810 TI - The effects of noradrenaline on neurones in the rat dorsal motor nucleus of the vagus, in vitro. AB - 1. Intracellular recordings were made from vagal motoneurones identified by antidromic stimulation in the dorsal motor nucleus of the vagus (d.m.v.) in slice preparations of rat medulla oblongata. 2. Noradrenaline (NA) applied by perfusion (0.01 microM to 1 mM) depolarized 55%, hyperpolarized 32% and produced a biphasic response (hyperpolarization followed by depolarization) in 9% of the d.m.v. neurones tested. 3. The NA effects persisted after complete elimination of synaptic inputs during perfusion with Ca2+-free high-Mg2+ solution, and therefore probably resulted from a direct action on the postsynaptic membranes. 4. The NA depolarization was blocked by prazosin and the NA hyperpolarization by yohimbine, but neither was blocked by propranolol or timolol. Phenoxybenzamine blocked both responses. The results indicate that NA depolarization is mediated by alpha 1 adrenoceptors and hyperpolarization by alpha 2-adrenoceptors. 5. The neurones which were depolarized by NA were also hyperpolarized by NA when the alpha 1 adrenoceptors were blocked by prazosin (all of seven neurones tested). This result suggests that most vagal motoneurones in the d.m.v. have both alpha 1-and alpha 2-adrenoceptors. 6. The NA depolarization was accompanied by a decrease in membrane conductance and the hyperpolarization by an increase in membrane conductance, both of which were measured under manual-clamp conditions. 7. The reversal potentials for the NA responses were around -85 mV in normal Ringer solution, and shifted as predicted by the Nernst equation when the extracellular K+ concentration was changed. 8. The inhibitory postsynaptic potentials evoked by focal electrical stimulation on the slice surface of the commissural part of the nucleus of the tractus solitarius (n.t.s.), which contains an A2 catecholaminergic cell group, were abolished by yohimbine. 9. The results suggest that NA modulates vagal output by decreasing or increasing the K+ conductance of d.m.v. neurones through alpha 1- or alpha 2-adrenoceptors. In addition, the A2 noradrenergic cell group within the n.t.s. may send inhibitory inputs to the d.m.v. PMID- 2895812 TI - Effects of stimulating the sympathetic innervation in bursts on submandibular vascular and secretory function in cats. AB - 1. The effects of continuous stimulation of the peripheral end of the ascending cervical sympathetic nerve were compared with those of intermittent stimulation, so arranged as to deliver the same total number of impulses, in cats under chloralose anaesthesia. 2. Continuous stimulation caused a flow of saliva at 5-10 Hz, but not at 2 Hz. In contrast, the same total number of impulses delivered intermittently in bursts elicited a prompt secretion at a frequency as low as 20 Hz for 1 s at 10 s intervals (corresponding to 2 Hz continuously) and a significantly higher rate of secretion at 50 Hz in bursts than that obtained in response to 5 Hz continuously. 3. Continuous stimulation also caused a rise in submandibular vascular resistance (s.v.r.), which persisted throughout the period of stimulation, and was followed immediately thereafter by an intense but transient fall in s.v.r. During stimulation in 1 s bursts, each burst was followed first by a brief rise in s.v.r. and shortly after by a fall. The balance between these two components varied widely between individual animals but often led to an overall fall in s.v.r. during stimulation i.e. complete reversal of the mean vascular effect. A further fall in s.v.r. was then recorded when the stimulus was discontinued. 4. Propranolol (1.0 mg/kg) reduced but failed to abolish the secretory response. It also altered the balance between the two phases of the vascular response slightly in favour of a rise in s.v.r. during stimulation, without apparently affecting the size of the after-dilatation. 5. Pre-treatment with dihydroergotamine (1.0 mg/kg) invariably blocked secretion and revealed a small vasodilator response during sympathetic stimulation with either pattern of stimulation; it also blocked the after-dilatation. 6. Following combined pre-treatment with propranolol and dihydroergotamine, to produce total adrenergic blockade, there was a small residual vasoconstrictor component which amounted to an increase in mean s.v.r. of about 20% during stimulation at 10 Hz continuously. This may have been due to release of neuropeptide Y (NPY). 7. Small but significantly greater amounts of NPY were released into the effluent blood during stimulation of the ascending cervical sympathetic nerve at 70 Hz in bursts than during continuous stimulation. No significant release of vasoactive intestinal peptide (VIP), somatostatin, bombesin, substance P or calcitonin gene related peptide (CGRP) was observed during stimulation at any frequency.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2895813 TI - Detection of alcohol-induced fatty liver by computerized tomography. AB - Computerized tomographic (CT) scanning of the liver was undertaken in 17 occasional and 19 heavy drinkers undergoing health screening. The median attenuation value of the liver (CT number) in occasional drinkers with normal liver function tests was 54.4 compared with 25.9 in the heavy drinkers (P less than 0.001). Fourteen of the heavy drinkers had a CT number below the lowest value observed in occasional drinkers with normal liver function, indicating reduced liver density due to fatty change. Serum gamma-glutamyl transpeptidase was normal in 36% of these individuals. A rise in CT number was observed in 4 out of 5 heavy drinkers who underwent a second scan after decreasing their alcohol consumption. These findings suggest that CT scanning provides a noninvasive and convenient method of screening for a fatty liver, which occurred to a variable degree in over 70% of the men who admitted to regularly taking 8 or more alcoholic drinks per day. PMID- 2895814 TI - Immuno-electronmicroscopy of fimbriae-like structures on Bordetella pertussis serotype 1.3. AB - Fimbriae-like filaments were demonstrated on the surface of Bordetella pertussis, serotype 1.3, by negative staining and electronmicroscopy. Immunoelectronmicroscopy with a monoclonal antibody specific for strains possessing agglutinogen 3, and colloidal gold, gave strong labelling of these structures. However, incubation with adsorbed polyclonal anti-agglutinogen 3 serum gave only weak labelling of the distal parts of the filaments and of the bacterial surface. The different binding patterns of the two antisera suggested that the epitopes involved were dissimilar. Thus, agglutinogen 3, as defined by conventional adsorbed sera, appeared to be associated with the fimbriae-like structures but was not necessarily identical to the fimbrial subunit protein. The monoclonal antibody, however was more likely directed against the subunits of the fimbriae-like structures on serotype 1.3 bacteria. PMID- 2895811 TI - Post-natal development of electrophysiological properties of rat cerebral cortical pyramidal neurones. AB - 1. The post-natal development of the electrophysiological properties of cortical layer V pyramidal neurons was investigated with intracellular recordings from rat sensorimotor cortical slices, in vitro. 2. At all ages post-natally (post-natal day 1 to day 36; P1-P36) neurons were capable of generating a train of Na+ dependent action potentials in response to intracellular injection of sufficient depolarizing current. During the second and third week post-natally, these action potentials changed substantially, becoming faster in both their rising and falling phases, shorter in duration, and larger in amplitude. 3. Both mature (greater than P21) and immature (P2-P4) cortical neurones could generate Ca2+ dependent action potentials only if a substantial portion of K+ conductances were blocked. The maximum rate of rise of Ca2+ spikes also increased with age. 4. The apparent input resistance, specific membrane resistance, and membrane time constant all decreased with age from P1 to P30. Immature neurones had I-V relationships that were substantially more linear than those of adult cells, although rectification was often present in both the hyperpolarizing and depolarizing range. Inward rectification in the depolarizing range was Na+ dependent and was substantially larger in mature versus immature neurones. 5. Single, or trains of, action potentials in immature neurones were followed by short duration (10-50 ms) and long duration (1-5 s) after-hyperpolarizations (a.h.p.s) respectively. The duration of the latter appeared to decrease with age. The presence of large a.h.p.s indicates that Ca2+ entry occurs during the action potential of immature, as well as mature, neurones. 6. Responses to intracellular injection of depolarizing current pulses indicated that immature neurones have frequency versus injected current (f-I) relationships which are in general less steep than those for adult neurones and more limited in terms of the range of firing frequencies. 7. Our results are consistent with the hypothesis that there is a considerable increase in the density of voltage-dependent ionic channels underlying the electro-responsiveness of cortical pyramidal neurones during post natal development. PMID- 2895815 TI - Complementarity of particles and pits in freeze-fractured hepatic and cardiac gap junctions. AB - Particles and pits of freeze-fractured gap junctions are considered as complementary structures despite the frequent observations of more regular and closer spacings of pits, ascribed to plastic deformation of particle arrays. Recently, however, the noncomplementarity of pits and particles in Purkinje fibers has been reported. To ascertain the relationship between both structures, gap junctions from fixed, cryoprotected liver and myocardium were investigated using spacing and density measurements and complementary replicas. In hepatocyte gap junctions, the center-to-center distances (mean +/- SD) among pits, 9.57 +/- 1.49 nm, and particles, 9.70 +/- 1.77 nm, are not significantly different. Density determinations yielded a slightly higher value for the pits, (11,510 +/- 830)/microns 2, than for the particles, (11,230 +/- 950)/microns 2. In the myocardium, the spacing of the regularly arrayed pits, 9.55 +/- 1.33 nm, barely exceeds the value of 9.44 +/- 1.62 nm for the particles, which show some clustering. However, the packing density for the pits, (10,090 +/- 740)/microns 2, appears a little higher than that of the particles, (9,890 +/- 920)/microns 2. As density and spacing measurements provided no decisive answers, the positions of individual pits and particles of complementary junctional faces were recorded on transparent sheets and compared. In this fashion, a one-to-one correspondence between particles and pits could be established, while small discrepancies may be attributed to plastic deformation. Moreover, the co-linearity of pits and particles may be suggested by the observation of a platinum grain in the center of many pits. PMID- 2895816 TI - Effects of adrenalectomy and corticosterone administration on mouse lung tumor susceptibility and histogenesis. AB - The effects of adrenalectomy (Ax) on urethan-induced lung tumors were determined in strains of mice that vary in their respective tumor susceptibilities: A/J (sensitive), BALB/cByJ (intermediate), and C57BL/6J (B6, resistant). Ax increased tumor number in both A/J (by 25%) and B6 mice (by 400%), but not in BALB/cByJ mice. The relative proportions of adenomas exhibiting the alveolar or papillary histological growth patterns were unchanged. Implantation of corticosterone containing pellets into adrenalectomized B6 mice restored tumor multiplicity to that of sham-operated mice and into adrenalectomized A/J mice reduced multiplicity below that of sham-operated mice. Corticosterone, therefore, regulates neoplastic development of mouse lung epithelial cells. PMID- 2895817 TI - Characteristics of vomiting associated with acute sustained release theophylline poisoning: implications for management with oral activated charcoal. AB - Vomiting in acute theophylline toxicity has assumed increased clinical importance since the introduction of multiple dose activated charcoal therapy. We performed a prospective study of 26 patients with acute overdose of sustained release theophylline to characterize vomiting, and its possible interference with the acceptance of activated charcoal. Twenty five of 26 patients vomited. The duration of vomiting correlated with both peak serum theophylline concentrations (p less than 0.001) and the duration of theophylline toxicity (p less than 0.001). Vomiting extended over 63% of the drug's absorptive phase (the time interval between ingestion and the peak level) and 49% of the elimination phase (the time interval between the peak level and decrease of theophylline level to less than 20 mcg/ml). Patients with peak serum theophylline concentrations less than 70 mcg/ml were able to accept larger amounts of activated charcoal than patients with serum theophylline concentrations greater than 70 mcg/ml (113 +/- 15 gms vs. 57 +/- 24 gms, p less than 0.05). Vomiting in acute sustained release theophylline toxicity is protracted, and limits the use of activated charcoal especially in patients with severe acute theophylline poisoning. PMID- 2895818 TI - [Anesthetic experience with 62 schizophrenic patients on chronic antipsychotic drugs]. PMID- 2895819 TI - [A case of ATL associated with monoclonal gammopathy preceded with laryngeal cancer]. PMID- 2895820 TI - [Molecular analysis and genetic diagnosis of hemophilia. b. Hemophilia B]. PMID- 2895821 TI - [Indices of the body's neurohumoral activity and hemodynamic types in hypertension]. AB - A study of neurohumoral parameters in patients with essential hypertension and different hemodynamic types demonstrated different patterns of hormonal change in patients with hyperkinetic, eukinetic and hypokinetic hypertension. Elevated blood tri-iodothyronine and thyroxine, seen in patients with hyperkinetic hemodynamic type, and increased catecholamine excretion in patients with hypokinetic hemodynamics may be indicative of the pathogenetic significance of the hormones in question for the formation of respective variants of essential hypertension. PMID- 2895822 TI - [Randomized treatment of hypertension patients (multicenter international research. The results of 1-year's observation)]. PMID- 2895823 TI - Absence of Kirsten-ras oncogene activation in B-cell chronic lymphocytic leukemia. AB - By using a combination oligonucleotide probe hybridization and restriction enzyme polymorphism analysis, a series of 48 cases of B-cell chronic lymphocytic leukemia were investigated for activating point mutations at codons 12, 13 and 61 of the K-ras proto-oncogene. A small series of acute leukemias (seven with acute lymphoblastic leukemia (ALL), 11 with acute myeloid leukemia (AML)) were examined in parallel. None of the cases of B-CLL contained detectable activating mutations of the K-ras gene at codon 12 (GGT-gly----GCT-ala) was detected at presentation. In both cases of acute leukemia, the mutation was restricted to one allele and could not be detected in remission samples. Those data suggest that activation of members of the ras oncogene family, typified by K-ras, may be less important in disease pathogenesis in leukemias such as B-CLL that arise from a more committed progenitor. PMID- 2895824 TI - Possible aetiological factors in leukaemias in Africa. AB - The hypothesis that the true incidence of c-ALL is relatively uniform throughout the world is not supported by experience in tropical Africa, where ALL is uncommon under five years of age. A high rate of spontaneous somatic mutation in pre-B cells may initiate the development of c-ALL, but its progress could be determined by (i) a leukaemogenic agent causing a second genetic event, (ii) the effects of intense antigenic barrage, either stimulating or suppressing pre-B cell mitosis, or (iii) genetic determinants. Epidemiological patterns in populations of low, intermediate and high socio-economic status may be classified I-III with increasing incidence of diagnosed T-ALL in children over five years and c-ALL in younger children, and subclassified A and B with decreasing incidence of BL. There may be two forms of AML, one similar to that seen in industrialized countries, the other occurring at high prevalence in African children of low socio-economic status, often presenting with chloroma, and perhaps associated with immune suppression secondary to malnutrition, malaria and other intercurrent infections. Uncontrolled exposure to petroleum and other chemicals, and the use of alkylating agents in treatment of neoplasms in young patients could emerge as important causes of ANLL in Africa. There are two varieties of CLL also, one similar to that seen in the western world, the other prevalent in adults below 45 years of age, especially women: transmission of a leukaemogenic agent is postulated, to which women are more susceptible due to immunosuppression during normal pregnancy. The human population and some subhuman primates of subSaharan Africa are the largest reservoir of HTLV-1, which shows association with B-CLL over 50 years of age and ATL. PMID- 2895825 TI - Monoclonal anti-Thy-1.2 antibody induced hematopoiesis in vivo. AB - The intravenous injection of a monoclonal anti-Thy-1.2 alloantibody (IgM class) induced a rapid increase in the number, and the ratio, of multipotent hematopoietic stem cells (CFU-S) in S-phase. The onset of hematopoiesis was thymus-independent. Reconstitution of lethally-irradiated mice with bone marrow cells from mice injected with antibody augmented the T-cell responsiveness to mitogens. No activation was observed in granulocyte/macrophage progenitors. The monoclonal antibody did not directly stimulate CFU-S in vitro, although hematopoietic activity could be found in the sera of antibody-injected mice. Immediately after injection, the antibody was found bound on Thy-1+ cells in spleen. No decrease in the number of peripheral T cells was seen. These results seem to indicate that Thy-1.2-positive cells bound with anti-Thy-1.2 alloantibody may secrete a factor which induces the proliferation of hematopoietic stem cells. PMID- 2895826 TI - Quantitative and qualitative studies of leukaemic cell dipeptidylpeptidases II and IV. AB - Cellular concentrations of dipeptidylpeptidases (DAP) II and IV were determined by fluorimetric assay in 152 cases of leukaemia and 24 permanent T-cell lines. Whilst its estimation appears to have few diagnostic applications, it was found that DAPII levels were generally higher in prolymphocytoid CLL variants (CLL-Pro) compared with "typical" CLL cases. Qualitatively, DAPII extracted from leukaemic B- and T-cells did not differ significantly with respect to molecular weight (Mr 82 kD: FPLC gel filtration) or substrate affinity (Km). Similarly, a single molecular weight species (Mr 189 kD) of DAPIV was also detected in all leukaemic sonicates examined although, in quantitative terms, increased DAPIV levels were primarily associated with a subgroup of CD4-positive postthymic malignancies. Studies of immature T-cell proliferations however indicated that DAPIV expression was unrelated to either stage of immunological differentiation or CD4 expression. No evidence of lineage restriction was found for either enzyme and it is concluded that variations in DAP cytochemical staining patterns reflect quantitative rather than qualitative differences. PMID- 2895827 TI - GABAergic, dopaminergic and cholinergic interaction in tremorine-induced tremors in mice. AB - Antitremor effects of systemically administered GABA agonists (GABA and sodium valproate) and GABA antagonists (bicuculline and picrotoxin) were studied in mice against tremorine-induced tremors. None of the GABA agonists were found to possess any antitremor effect, whereas GABA antagonists were found to possess protective effect against tremorine-induced tremors. Simultaneous administration of GABA agonists with sub-effective doses of anticholinergic agent (scopolamine) did not potentiate antitremor effect of scopolamine, whereas GABA antagonists and effective doses of scopolamine when administered simultaneously resulted in antagonism of protective effect of scopolamine. Similarly, when GABA agonists and sub-effective doses of dopaminergic agent, bromocriptine, were administered simultaneously, the protective effect of bromocriptine was potentiated. When GABA antagonists and effective doses of bromocriptine were administered simultaneously, the protective effect of bromocriptine was antagonized. The modification of the protective effect of anticholinergic and dopaminergic agents by GABAergic agents has been explained on the basis of neurotransmitter interaction. PMID- 2895828 TI - Clinical efficacy of a new, enhanced-potency, inactivated poliovirus vaccine. AB - The 1986-87 outbreak of paralytic poliomyelitis in Senegal, with 676 reported cases, provided an opportunity to evaluate the efficacy of an enhanced-potency inactivated poliovirus vaccine (N-IPV) in the Kolda region, where this vaccine has been used since 1980. 89 cases, confirmed to have poliomyelitis with residual paralysis, were enrolled in a case-control study, up to 5 matched controls being obtained for each case. The clinical efficacy for one dose of N-IPV was 36% (95% confidence interval 0%, 67%) and for two doses was 89% (95% CI 62%, 97%). PMID- 2895829 TI - Calcitonin for prevention of postmenopausal bone loss. AB - A 2-year randomised pilot study was conducted in 70 patients to see whether the osteoclast-inhibiting effect of calcitonin would reduce postmenopausal vertebral bone loss. An oestradiol-treated group was included in the study as a positive control since oestrogens are known to be effective. Calcitonin reduced vertebral bone loss in doses above 250 micrograms human calcitonin (50 international units) a week, and at this dose was as effective as oestradiol. PMID- 2895830 TI - Cellular anti-GP120 cytolytic reactivities in HIV-1 seropositive individuals. AB - Forty-one patients seropositive for human immunodeficiency virus type 1 (HIV-1) were assessed for cell-mediated cytotoxicity (CMC) against autologous target cells bearing the major envelope glycoprotein of HIV-1, gp120. Effector lymphocytes from over 85% of seropositive patients showed CMC specific for gp120 coated targets, whereas seronegative individuals had no detectable CMC. As a group, symptomless individuals had the highest levels of CMC; patients with AIDS related complex and AIDS showed progressively diminished reactivity. The gp120 specific CMC was mediated by a population of non-T-cell effectors phenotypically resembling NK/K cells. Cytolysis was not restricted by major histocompatibility complex determinants, as shown by killing of heterologous gp120-adsorbed targets and of HIV-1-infected cell-lines. Gp120-specific CMC was highly augmented in the presence of interleukin 2, so it may be possible to develop therapeutic strategies aimed at destruction of virus-producing cell reservoirs in infected individuals through stimulation of HIV-specific host CMC. PMID- 2895831 TI - Overuse syndrome: a muscle biopsy study. AB - Biopsy specimens were taken from the affected first dorsal interosseous muscle in 29 women with painful chronic overuse syndrome and from 8 volunteer controls. Structural differences in samples from the women with overuse syndrome included increased type 1 fibres with type grouping, decreased type 2 fibres, type 2 fibre hypertrophy, increased internal nuclear count, mitochondrial changes, and various ultrastructural abnormalities. These changes were related to clinical severity, and point to an organic cause for the syndrome. PMID- 2895832 TI - Red-cell-volume distribution curves in diagnosis of glomerular and non-glomerular haematuria. AB - The distribution curves of urinary red-blood-cell (RBC) size were obtained from automated blood-cell analysis in 146 patients with definite causes of haematuria. In 65 of 67 patients (97%) with haematuria and glomerulonephritis demonstrated by renal biopsy, urinary RBC had an irregular and asymmetrical distribution with RBC size showing a much smaller volume than that of venous RBC. This "glomerular" distribution contrasted with the "non-glomerular" normal distribution when the peak for RBC was at a larger volume than that for peripheral RBC. In 46 of 47 patients with haematuria who had lower urinary tract lesions other than infection, a non-glomerular distribution was obtained; 30 of these cases also showed glomerular distribution, and were classified as "mixed". All 32 patients with urinary tract infection had either a glomerular or mixed distribution, suggesting that they excreted distorted and dysmorphic urinary RBC. After excluding infections, this simple, rapid, reproducible, and non-invasive technique provides reliable information in distinguishing glomerular bleeding from other causes of haematuria. PMID- 2895833 TI - Isolated duodenal tamponade for treatment of bleeding duodenal ulcer. PMID- 2895834 TI - Obstruction or reflux in gallstone-associated acute pancreatitis? PMID- 2895836 TI - Screening for hypertension in childhood. PMID- 2895835 TI - Rabies vaccine failures. PMID- 2895837 TI - Hyperlipidaemia after renal transplantation. PMID- 2895838 TI - Mechanisms for the early mortality reduction produced by beta-blockade started early in acute myocardial infarction: ISIS-1. ISIS-1 (First International Study of Infarct Survival) Collaborative Group. AB - In a large randomised trial of early beta-blockade in acute myocardial infarction (ISIS-1), almost all the reduction in mortality associated with the use of atenolol occurred on the day of admission or on the subsequent day. To help determine the mechanisms that might be responsible for this retrospective observation, case notes were obtained for British, Irish, and Scandinavian patients who died during this early period. Of 217 early deaths adequate records were available for 193 (79 allocated atenolol and 114 allocated control). In the atenolol group, necropsy had shown cardiac rupture in 5 patients, and a further 15 in whom necropsy had not been done had had electro-mechanical dissociation (total, 20 early deaths from these causes); among control patients the corresponding numbers were 17 and 37 (total, 54 such deaths). Electro-mechanical dissociation was probably a manifestation of acute rupture, and the observed difference in the numbers with this complication was responsible for much of the difference in early mortality. There was a slightly higher incidence of fatal ventricular fibrillation and aortic dissection in the control group, and of bradycardia/asystole in the atenolol group. The data did not indicate any substantial contribution from mechanisms such as limitation of infarct size or prevention of reinfarction or cardiac arrest. PMID- 2895840 TI - Dosage and safety of long-term suppressive acyclovir therapy for recurrent genital herpes. AB - 131 patients with frequently recurring genital herpes were treated for 1 year with reducing doses of oral acyclovir. The time to first recurrence in patients who commenced therapy on 400 mg twice a day was statistically significantly shorter than those on 200 mg four times a day (p less than 0.02) and as the total daily dose and frequency of therapy were lowered so the time to first recurrence was shortened. By the end of 60 days on 200 mg once a day (the lowest daily dose) 56% of patients had recurrences. Patients showed a marked reduction in the frequency of recurrence during therapy (from a mean of 1.1 per 28 days before to 0.11 during treatment, p = 0.0001). After stopping treatment the frequency of recurrences (0.71 per 28 days) was significantly less than the pre-treatment period (p = 0.001). No important side-effects were seen. It is concluded that long-term suppression with acyclovir is safe and effective for patients with recurrent genital herpes. PMID- 2895839 TI - The role of bone-marrow transplants after nuclear accidents. AB - The probability that bone-marrow transplantation will be beneficial after nuclear accidents depends on several factors, including circumstances of the accident, degree of damage in other body systems, and radiation dose. Transplant-related variables, such as donor-recipient histocompatibility and post-transplant immune suppression, are also important. The benefits of transplantation may result from transient or permanent haemopoietic reconstitution. The balance of potential benefits versus risks should be individually calculated for each accident and each patient; generalisations are likely to result in untenable conclusions. PMID- 2895841 TI - Anorexia nervosa in 1888. PMID- 2895842 TI - Treatment of osteosarcoma. PMID- 2895843 TI - Randomised trial of memory training in the over-60s. PMID- 2895844 TI - ABO alloimmunisation after intravenous immunoglobulin infusion. PMID- 2895845 TI - Small-intestinal transit time in the elderly. PMID- 2895846 TI - Radiation, cancer risk, and the new dosimetry and ICRP inaction. PMID- 2895847 TI - Pesticide toxicity or hypoglycine A poisoning (Ivory Coast, 1984)? PMID- 2895848 TI - Immunological reactivity and bioactivity of tumour necrosis factor. PMID- 2895849 TI - Water standards for fluoride. PMID- 2895850 TI - Monoclonal antibodies to HIV in a non-infected, immunised volunteer. PMID- 2895851 TI - Group-specific component and AIDS: erroneous data. PMID- 2895852 TI - HIV and polyarthritis. PMID- 2895853 TI - Cure of Pseudomonas aeruginosa infection in neutropenic patients by continuous infusion of ceftazidime. PMID- 2895854 TI - Updated Kiel classification. PMID- 2895856 TI - Chronic sinus node disease and coronary artery disease. PMID- 2895855 TI - Problem with aspirin as antithrombotic agent in coronary artery disease. PMID- 2895857 TI - Thrombolytic therapy for myocardial infarction. PMID- 2895858 TI - Diabetic retinopathy: a self-sustaining process. PMID- 2895860 TI - Violence, nursing, and inpatient psychiatry. PMID- 2895859 TI - Prophylactic low-dose aspirin and dipyridamole in pregnancy. PMID- 2895861 TI - Children, violence, and Southern Africa. PMID- 2895862 TI - Distinction awards. PMID- 2895864 TI - Death of a soldier. PMID- 2895863 TI - Editorial freedom in South Africa. PMID- 2895865 TI - Accuracy of bibliographic data bases. PMID- 2895866 TI - Clinical characteristics of Campylobacter jejuni and C coli enteritis. PMID- 2895867 TI - Growth in children treated for acute lymphoblastic leukaemia. PMID- 2895868 TI - Subcutaneous apomorphine in Parkinson's disease. PMID- 2895869 TI - Legionella: a case for culture. PMID- 2895870 TI - Maternal hepatitis B infection affects fetal IgE synthesis. PMID- 2895871 TI - Raynaud's phenomenon and cryoglobulinaemia associated with the use of recombinant human alpha-interferon. PMID- 2895872 TI - Bone marrow transplantation from programmed donor: one year on. PMID- 2895873 TI - Chloride-free oral rehydration solutions. PMID- 2895874 TI - New dual form of porphyria. PMID- 2895875 TI - Renal allograft survival in transfused and non-transfused patients. PMID- 2895876 TI - Natural history of localised prostatic cancer. PMID- 2895877 TI - Lipid deposition in central venous catheters: a solution. PMID- 2895878 TI - Short-course alpha-interferon therapy in severe unresponsive immune thrombocytopenic purpura. PMID- 2895879 TI - Infant nutrition and adult health. PMID- 2895880 TI - Retroviruses in monocytes from patients with breast cancer. PMID- 2895881 TI - Carbon dioxide, brain damage, and cardiac surgery. PMID- 2895882 TI - Blue dyes in reconstructive surgery. PMID- 2895884 TI - Yawning. PMID- 2895883 TI - Recombinant human granulocyte-macrophage colony-stimulating factor produces fever. PMID- 2895885 TI - AIDS in the UK. PMID- 2895887 TI - Identification of restriction-fragment-length polymorphisms in genomic DNA of the lesser snow goose (Anser caerulescens caerulescens). AB - A genomic library of partially EcoRI-digested DNA from the lesser snow goose, Anser caerulescens caerulescens, was constructed in the phage vector Charon 4. Phage containing only unique sequences were identified by screening plaques with 32P-labeled genomic DNA. Restriction-fragment-length polymorphisms (RFLPs) were identified by probing DNA from 11-13 male birds from the breeding colony at La Perouse Bay. Of the 17 probes examined, all detected RFLPs with at least one of EcoRi, HindIII, Msp1, and Taq1. Several of them identified highly variable regions with multiple alleles. These RFLPs are valuable DNA markers that can be used for (1) the examination of DNA variation, relatedness, and genetic distance and (2) assessing paternity and maternity. These data suggest that there are higher levels of variation of DNA sequence in birds than had previously been thought to exist. PMID- 2895886 TI - [Results of treatment of ulcer hemorrhages]. AB - The results of 270 patients, admitted from 1978 to 1985 because of upper gastrointestinal bleeding from ulcers or erosions were analysed retrospectively. Chronic peptic ulcers were the most common bleeding sites (192 patients, 71%). 49 patients (18%) bled from acute lesions and 29 (11%) from drug-induced ulcers. 53% of all patients exhibited an oozing hemorrhage (type Forrest 1 b) during emergency endoscopy. Within the eight-year-period hospital mortality dropped from 18% to 8%. In parallel the prognosis of oozing bleeding improved. In this period the patients were more often treated with secretin or somatostatin. Hence the frequency of emergency operations for patients with oozing bleeding could be reduced from 44% in 1978 to 10% in 1985 and the death rate from 22% to 5%. PMID- 2895888 TI - Investigations into the genotoxic potential of loxtidine, a long-acting H2 receptor antagonist. AB - Loxtidine, a potent, non-competitive histamine H2-receptor antagonist was evaluated for genotoxic potential using a range of short-term mutagenicity assays. Unequivocally negative results were obtained in a Salmonella/plate incorporation assay and a liquid pre-incubation assay (using S. typhimurium strains TA1535, TA100, TA1537, TA1538 and TA98), a fluctuation assay [using Escherichia coli strains WP2, WP2 uvrA (R46) and 343/113 lys60 (R46)], a gene conversion assay (using Saccharomyces cerevisiae JD1) and a human peripheral lymphocyte cytogenetic assay. All of these in vitro tests were carried out in the presence and absence of rat liver S9 mix. In addition, the major metabolites of loxtidine in the rat were also negative in the same range of microbial mutagenicity assays. Loxtidine was inactive in the mouse micronucleus test after oral administration. The potential nitrosatability of loxtidine was investigated using an expanded version of the WHO Nitrosation Assay Procedure, and detectable quantities of mutagenic nitroso-species were not formed. The subsequent appearance of carcinoid tumours within the gastric fundus of rodents treated orally with loxtidine for most of their natural lifespan, led to additional assays being carried out on this compound to determine whether the tumorigenic effects were due to alternative mutagenic mechanisms. Negative results were obtained in an in vitro unscheduled DNA synthesis assay using primary rat hepatocytes, and an assay for spindle damaging agents using Muntjac skin fibroblasts. It can be concluded from these results that loxtidine is unlikely to be a genotoxic carcinogen. The increase in carcinoid tumour incidence observed in rats and mice after loxtidine treatment was probably related to the prolonged achlorhydria produced by this potent unsurmountable histamine H2-receptor antagonist. PMID- 2895889 TI - Somatostatin receptor subtypes in the clonal anterior pituitary cell lines AtT-20 and GH3. AB - The functional and biochemical characteristics of somatostatin (somatotropin release-inhibiting factor) (SRIF) receptor subtypes were examined in the clonal pituitary cell lines AtT-20 and GH3. SRIF inhibits evoked calcium influx into each of these cell lines. The rank order of potencies of structural analogues of SRIF to inhibit calcium influx into GH3 versus AtT-20 cells was different. Inhibitory actions of SRIF on calcium influx desensitized in AtT-20 cells but not GH3 cells. The biochemical properties of the SRIF receptor subtypes in AtT-20 and GH3 cells were assessed by photoaffinity labeling of each receptor with the nonreducible SRIF analogue [125I]CGP 23996 and the photocrosslinking agent n hydroxysuccinimidyl-4-azidobenzoate. The covalently labeled receptors in both cell lines had the same size, 55 +/- 5 kDa, as assessed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The covalent binding of [125I]CGP-23996 to GH3 and AtT-20 cell membranes was blocked by 1 microM SRIF, somatostatin 28, Trp8 SRIF and was GTP sensitive. Analysis of the labeled receptors in GH3 and AtT-20 cell membranes by two-dimensional polyacrylamide gel electrophoresis indicated that they were of similar charge (pI = 6-6.5) and that they comigrate when applied together. Proteolysis of the GH3 and AtT-20 cell SRIF receptors with Staphylococcus aureus V-8 and thermolysin revealed similar peptide maps. Pretreatment of AtT-20 cells with different stable SRIF analogues abolished the subsequent equilibrium or covalent labeling of the SRIF receptor with [125I]CGP 23996. Similar treatment of GH3 cells did not reduce the covalent labeling of the SRIF receptor by [125I]CGP 23996. These studies indicate that the functional characteristics of SRIF receptors in GH3 and AtT-20 cells are different. However, clear differences in the biochemical properties of these receptor subtypes were not observed. Subtle variations in the structure of the SRIF receptors may therefore be responsible for the functional differences. PMID- 2895890 TI - [Restriction map of permuted DNA of Erwinia carotovora temperate bacteriophage 59]. AB - The cyclic permutation and terminal redundancy were found in the genomes of Erwinia carotovora temperate bacteriophage 59 by electron microscopic studies. The headful mechanism for bacteriophage DNA cleavage and packaging during the phage morphogenesis was confirmed by the restriction analysis technique. Restriction map of the bacteriophage 59 DNA was constructed for restriction endonucleases BamHI, Bg1II, Eco31, Sa1I, SmaI, EcoRI. PMID- 2895892 TI - Emotional aspects of paediatric hospitalization: guidelines for management. PMID- 2895891 TI - [Identification of protein products of the operon for leukocytosis (lymphocytosis)-stimulating factor from Bordetella pertussis cloned in Escherichia coli]. AB - The hybrid plasmid pRH119 was constructed on the basis of vector plasmid pUC19 and shown to carry Bordetella pertussis PT operon in the same transcriptional orientation with the lac-promoter of the vector plasmid. Expression of PT genes in E. coli cells harbouring pRH119 was not registered. Weak expression of PT genes was found by immunoscreening of recombinant clones in situ with antiserum against PT when PT genes were put closer to lac-promoter. 0.95 kb SalGI fragment was deleted from pRH119. The derivative plasmid pRH122 was digested by SalGI and the ends were polymerized to "blunt" by polIK and ligated. The obtained plasmid pRH122K was deleted for 40 bp in XbaI site by Bal31 deletion. The lysate of E. coli cells harbouring the resulting plasmid pRH134 passed through Sepharose 4B with covalently bound immunoglobulins from antiserum against PT. The eluted protein contains S2 multimers identified by immunoblotting. The experiments with CHO-cells and active mice protection have shown the absence of S2 multimers protectiveness. PMID- 2895893 TI - The origin of MHC class II gene polymorphism within the genus Mus. AB - The I region of the major histocompatibility complex (MHC) of the mouse (H-2) contains a tightly-linked cluster of highly polymorphic genes (class II MHC genes) which control immune responsiveness. Speculation on the origin of this polymorphism, which is believed to be essential for the function of the class II proteins in immune responses to disease, has given rise to two hypotheses. The first is that hypermutational mechanisms (gene conversion or segmental exchange) promote the rapid generation of diversity in MHC genes. The alternative is that polymorphism has arisen from the steady accumulation of mutations over long evolutionary periods, and multiple specific alleles have survived speciation (trans-species evolution). We have looked for evidence of 'segmental exchange' and/or 'trans-species evolution' in the class II genes of the genus Mus by molecular genetic analysis of I-A beta alleles. The results indicate that greater than 90% (28 out of 31) of the alleles examined can be organized into two evolutionary groups both on the basis of restriction site polymorphisms and by the presence or absence of a short interspersed nucleotide element (SINE). Using this SINE sequence as an evolutionary tag, we demonstrate that I-A beta alleles in these two evolutionary groups diverged at least three million years ago and have survived the speciation events leading to several modern Mus species. Nucleotide sequence comparisons of eight Mus m. domesticus I-A beta alleles representing all three evolutionary groups indicate that most of the divergence in exon sequences is due to the steady accumulation of mutations that are maintained independently in the different alleles. But segmental exchanges between alleles from different evolutionary groups have also played a role in the diversification of beta 1 exons. PMID- 2895894 TI - Transduction of endogenous envelope genes by feline leukaemia virus in vitro. AB - Feline leukaemia viruses (FeLV) are exogenous retroviruses that can be detected in most cats with leukaemia, aplastic anaemia, myeloproliferative diseases and fatal immunosuppression. FeLV isolates have been divided into three subgroups, based on the viral envelope-determined properties of interference and host range in vitro. FeLV-A is present in all natural isolates and is generally minimally pathogenic. FeLV-B is found with FeLV-A in isolates from approximately 40% of natural infections and in a higher percentage of cats with lymphoma. Following the fundamental observations of genetic reassortment of avian retroviruses with endogenous viral genes and the origination of lymphomagenic viruses during the ontogeny of AKR mice, we show here that transfection of feline cells with FeLV-A DNA results in its recombination with endogenous FeLV-related sequences to produce viruses with the structural and host range properties of FeLV-B. Thus in vitro propagation of a retrovirus may result in the generation of variants with very different properties. PMID- 2895895 TI - A highly polymorphic locus very tightly linked to the Huntington's disease gene. AB - The genetic defect in Huntington's disease (HD), an inherited neuropsychiatric disorder of unknown etiology, has not been defined. The discovery of linkage between HD and the DNA marker D4S10(G8) raised the possibility of isolating the disease gene on the basis of its chromosomal location, in addition to providing a limited presymptomatic test for the late onset disorder. But it has been difficult to isolate other DNA markers nearer to the HD gene, and this has hampered attempts to identify the disease locus and limited the applicability and accuracy of predictive testing. Recently, several new DNA markers from the region of the genome near the HD gene have been isolated using a directed cloning strategy. We describe here the characterization of one of these new markers, D4S95, a highly polymorphic locus which displays no recombination with the HD gene in the families tested. The high degree of polymorphism at this locus and its proximity to the HD gene make it extremely useful for predictive testing and as a new starting point for attempts to clone the disease gene. PMID- 2895896 TI - Divergent homeo box proteins recognize similar DNA sequences in Drosophila. AB - A member of a small group of genes in Drosophila that define the segmentation pattern of the early embryo even-skipped (eve), which plays a key role in a network of interactions among segmentation genes. It appears to control morphogenesis by regulating the expression of the segmentation gene engrailed (en), and by autoregulating its own expression (M. Frasch and M.L., in preparation). Here we show that these regulatory interactions could occur at the level of transcription as a full-length eve protein binds with high affinity to specific sequences located near the 5' ends of the eve and en genes. The en binding sites contain at least one copy of a 10-base pair consensus sequence: T-C A-A-T-T-A-A-A-T. In contrast, the 5' eve binding sites are relatively G-C rich and do not share obvious similarities with the 10-base pair consensus sequence associated with en. Other homeo box proteins can recognize both classes of eve binding sites, lending support to the proposal that regulatory interactions among homeo box genes involve a competition of different homeo box proteins for similar cis regulatory sequences. PMID- 2895897 TI - Periodic oscillation of intracranial pressure in ventricular dilation: a preliminary report. AB - Artificial pressure waves (PWs) were generated by manual inflation of a balloon in the trigonum of the lateral ventricle in seven adult mongrel dogs with normal cerebrospinal fluid (CSF) circulation. In 14 of 16 series of continuous appearances of artificial PWs, local shifts of the brain were successfully monitored using small strain-gauge sensors at the periventricular structures in these animals. Of the 14 series, 13 showed displacements of the periventricular structures, suggesting ventricular dilation. These results did not always correlate with macroscopic findings. They are thought to be due largely to periventricular oedemas and, in part, non-uniform dilations of the ventricles during PWs. We conclude that a water hammer formed by reflection of an increased pulse pressure of PWs at the site of CSF absorption causes a shift of CSF from the ventricle to the periventricular structures through the wall of the ventricle. This phenomenon appears amplified in patients with impaired CSF absorption. Thus, PWs have a pathological role in the progress of ventricular dilation in patients with normal pressure hydrocephalus. PMID- 2895898 TI - The geomagnetic field: a factor in cellular interactions? I. Magnetism and Schwann cell-axon interaction in the peripheral nerves of the newborn rat. AB - Axonal ensheathment and myelination, one form of axon-sheath cell interaction, was studied under normal earth magnetism, in the absence of terrestrial magnetic field, and under a 5 G (0.0005 T) magnetic field. Results indicate that the geomagnetic field is necessary for the fundamental biological activity of axonal ensheathment and myelination. The exact mechanism of action remains obscure. PMID- 2895899 TI - Three-dimensional computed tomographic scans in the planning of procedures for reconstructive craniofacial surgery. AB - Three-dimensional computed tomographic (3D CT) scans were used in the assessment of three cases being considered for craniofacial reconstructive surgery; the first patient had a frontal encephalocele, the second an orbital encephalocele and the third an apparent asymmetry of the face due to cervical scoliosis caused by developmental defects of the upper two cervical vertebrae. The 3D CT scans provided information which was of great help in deciding how best to manage each case. PMID- 2895900 TI - Hyperglycaemia protects against neuronal injury around experimental brain infarcts. AB - Regional glucose utilization was measured in the rat brain after occlusion of the middle cerebral artery. Normoglycaemic rat had increased glucose use in the cerebral cortex adjacent to the infarct. A fraction of the nerve cells were irreversibly injured in this region. In hyperglycaemic rats, the glucose metabolism remained normal and no nerve cell loss was found around the infarct. The findings indicate that hyperglycaemia protects against nerve cell injury in the areas next to experimental brain infarcts. PMID- 2895901 TI - Autoregulatory response of pial vessels in the cat. AB - Pial vessel responses to mean arterial pressures (MAP) between 40 and 160 mmHg, induced by withdrawal and reinfusion of blood, were studied in twelve cats under barbiturate- and N2O-anaesthesia, using the cranial window technique and videoangiometry. Very minor changes of pial arterial calibres were noted between MAP 80 and 120 mmHg. During further reduction of MAP, small arteries dilated more than large arteries and measured 43 +/- 4.6% and 30 +/- 1.9% at MAP 40 mmHg, respectively. When MAP was elevated to 140 mmHg, large arteries constricted more than small ones; at MAP 160 mmHg, however, they started to redilate, while small arteries continued to constrict to -13 +/- 2.3%. Within the autoregulatory range, pial veins remained unchanged; at MAPs of 40 and 160 mmHg, venous calibre variations remained below 10%. PMID- 2895902 TI - Underlying mechanisms of facilitation and depression of transmitter release. The role of calcium in synaptic transmission. AB - The internal functioning of a mathematical model describing synaptic transmission and accounting for both facilitation and depression is analysed. Simulation studies reproduce all salient characteristics of both phenomena during repetitive nerve stimulation. Specifically, the analysis reveals that 1. facilitation and depression may be explained in terms of the dynamics of a common process, 2. calcium ions exert a similar influence on this process during the development of both phenomena and 3. the accumulation of an active calcium residue inside the nerve terminal is not absolutely necessary to account for facilitation. Rather, it is proposed that such a residue constitutes an important factor exerting an influence on the development and control of longer term phenomena such as augmentation and potentiation, the two components of post-tetanic potentiation. PMID- 2895903 TI - Microvascular anatomy of Heubner's recurrent artery. AB - The microvascular anatomy of Heubner's recurrent artery (RAH) was studied in 50 human brains (100 hemispheres) using acrylic paint under the operative microscope. The recurrent artery of Heubner was always found as a single vessel in 28 cases (28%) and multiple vessels in 72% (double vessels in 48%, triple in 23% and quadruple in 1%). Altogether 197 RAH were found in 100 hemispheres, averaging 1.97 arteries per hemisphere. In 44 instances, it originated from the proximal part of the A1-segment of the anterior cerebral artery. The diameters of the RAH ranged from 0.4 to 1.5 mm. Their vascular territory was variable. Four groups of distributing branches were found in the RAH: frontal and hypothalamic, olfactory, perforating and sylvian-fissure branches. In 12 hemispheres, anastomoses were found between the perforating branches of the RAH and the middle cerebral artery. In five cases (5%) anastomoses were present between the perforating branches of the MCA and the olfactory branch of the RAH. In one case (1%), an anastomosis was found between two RAH. PMID- 2895904 TI - The role of calcium in parenchymal cell injury in subarachnoid haemorrhage. AB - Experimental subarachnoid haemorrhage and intraparenchymal haematoma were produced in 20 cats serving as a model for parenchymal cell injury in patients with head trauma. There was a typical and constant cellular membrane dysfunction characterized by K+ outflux and Ca2+ influx. It appears that both of these events have a major influence on subsequent development of cellular dysfunction, anatomically characterized as cellular swelling. In addition, the calcium influx appears to have a specific role in the cell membrane destruction process by initiating an autolytic destruction of cell membranes. This mechanism may be crucial in the development of secondary irreversible injuries in cells destabilized, but not completely destroyed, at the time of the initial trauma. PMID- 2895905 TI - Stereotactic drainage of brain abscesses. AB - Between 1981 and 1986, 16 patients with brain abscesses underwent computed tomography (CT) guided stereotactic aspiration with (n = 5) or without (n = 11), catheter drainage. Infectious sources were found in 11 patients; 6 patients had concomitant immune suppression. Bacterial or mixed toxoplasmic-fungal or toxoplasmic-viral abscesses were diagnosed in 14 patients. After prolonged antimicrobial treatment, follow-up clinical and radiological evaluations confirmed abscess resolution in 12 patients. The abscess size was smaller in four patients, three of whom died 30-60 days after surgery due to overwhelming systemic opportunistic infections. One patient with a tuberculous brain abscess continued to exhibit gradual abscess regression one year after beginning three drug antituberculous therapy. No surgical mortality occurred but two patients required evacuation of post-operative intracerebral haematomas that resulted from over-vigorous abscess aspiration. CT stereotactic drainage is a safe and effective technique to diagnose and treat brain abscesses and is mandatory for small or deep-seated lesions. Empirical therapy of suspected brain abscesses is rarely warranted in the era of CT stereotactic surgery. PMID- 2895906 TI - BuSpar is clarified. PMID- 2895907 TI - Neuroleptic malignant syndrome. PMID- 2895908 TI - Symposium: Questioning the efficacy and safety of antihistamines in the treatment of upper respiratory infection. Introduction. PMID- 2895909 TI - Ineffectiveness of oral terfenadine in natural colds: evidence against histamine as a mediator of common cold symptoms. AB - The role of histamine in the pathogenesis of infectious rhinitis is unclear, as is the efficacy of antihistaminic drugs in the treatment of the common cold. This study evaluated the short-term efficacy of oral terfenadine (Seldane) in the treatment of the common cold. Over a 5-week period, the authors recruited 250 adults who had developed cold symptoms within 6 to 48 hours prior to enrollment. Volunteers had a primary complaint of runny or stuffy nose; at least one other respiratory symptom; no fever or exudative pharyngitis; and no history of atopy, sinusitis, or use of cold preparations within 1 week of enrollment. Out of the eligible subjects, 126 were randomly assigned terfenadine (60 mg), and 124 received placebo. Volunteers self-administered either terfenadine or placebo twice a day on Days 1, 2 and 3, and a final dose on the morning of Day 4. They also recorded the severity of their clinical symptoms (runny nose, sniffles, sneezing, postnasal drip, cough and sore throat) on symptom cards. Both groups reported similar severity scores throughout the treatment period. Average symptom burdens declined at almost identical rates for both groups. Terfenadine was well tolerated and had a low incidence of side effects. According to subject evaluation, terfenadine was no more effective than placebo. The mean +/- SD score of global efficacy was 2.2 +/- 1.1 in the terfenadine group and 2.1 +/- 1.3 in the placebo group (P = NS). Slightly fewer terfenadine recipients (41%) than placebo recipients (48%) said they would use the study medication again for treating cold symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2895910 TI - Multicenter trial of cryotherapy for retinopathy of prematurity: preliminary results. Cryotherapy for Retinopathy of Prematurity Cooperative Group. AB - We report the preliminary 3-month outcome of a multicenter randomized trial of cryotherapy for treatment of retinopathy of prematurity (ROP). Transscleral cryotherapy to the avascular retina was applied to one randomly selected eye when there was threshold disease (defined as five or more contiguous or eight cumulative 30 degree sectors [clock hours] of stage 3 ROP in zone 1 or 2 in the presence of "plus" disease). An unfavorable outcome was defined as posterior retinal detachment, retinal fold involving the macula, or retrolental tissue. At this writing, 172 infants had been examined 3 months after randomization. An unfavorable outcome was significantly less frequent in the eyes undergoing cryotherapy (21.8%) compared with the untreated eyes (43%). While the surgery was stressful, no unexpected complications occurred during or following treatment. These data support the efficacy of cryotherapy in reducing by approximately one half the risk of unfavorable retinal outcome from threshold ROP. PMID- 2895911 TI - MboI RFLP at the human renin (ren) gene locus. PMID- 2895912 TI - Pvu-II RFLP at the human lipoprotein lipase (LPL) gene locus. PMID- 2895913 TI - A biallelic DNA polymorphism of the human beta-2-adrenergic receptor detected by Ban I-Adrbr-2. PMID- 2895914 TI - An anonymous DNA segment pTP5E (D5S70) maps to the long arm of chromosome 5 and identifies a Taq I polymorphism. PMID- 2895915 TI - Probe 8B/E5' detects a second RFLP at the human liver/bone/kidney alkaline phosphatase (ALPL) locus. PMID- 2895916 TI - Two PstI RFLPs in the PCCB gene on the long arm of chromosome 3. PMID- 2895918 TI - Bsm I RFLP at the human apolipoprotein AI-CIII gene complex locus. PMID- 2895917 TI - Viral K-ras detects two TaqI polymorphisms, one for KRAS1 on chromosome 6 and the other for KRAS2 on chromosome 12. PMID- 2895919 TI - Two Pvu II RFLPs recognized by a human immunoglobulin alpha heavy chain probe (IgHA1). PMID- 2895920 TI - HinfI RFLP downstream to the human HRAS1 gene. PMID- 2895921 TI - Oncology Nursing Society. May 4-7, 1988. Thirteenth Annual Congress, Pittsburgh, Pennsylvania. PMID- 2895922 TI - [Polymorphism of the length of DNA restriction fragments in clinical practice]. PMID- 2895923 TI - Urticaria--a challenge in diagnosis and treatment. AB - Urticaria can be caused by a multitude of factors, both internal (eg, ingested drugs or foods) and external (eg, skin contact, heat, cold). Skin testing, ice cube testing, skin biopsy, and food-challenge testing are some of the methods that can help link cause and effect. Acute urticaria may require the administration of epinephrine and diphenhydramine or a lowering of the antigen dose in an allergy shot. Chronic urticaria is plainly visible in clinical presentation but is more elusive in diagnosis and treatment. It constantly challenges the physician's investigative acumen. PMID- 2895924 TI - Tolerance to the anticonvulsant effect of clorazepate and clonazepam in mice. AB - The rate of development of tolerance to the benzodiazepines clorazepate and clonazepam against pentetrazole-induced seizures in mice was compared. Treatment with clorazepate (0.1% solution as drinking water) for 21 days led to tolerance beginning at day 7. When mice were treated with clonazepam (0.5 mg/kg twice daily intraperitoneally), tolerance was evident already at the fourth day of treatment. Twenty-four hours after cessation of treatment the seizure threshold was significantly decreased after treatment with both drugs. Clorazepate, a prodrug of the main metabolite of diazepam, desmethyldiazepam, regards further interest for anticonvulsant therapy because of a relatively slow onset of tolerance. PMID- 2895925 TI - On the active site thiol of gamma-glutamylcysteine synthetase: relationships to catalysis, inhibition, and regulation. AB - gamma-Glutamylcysteine synthetase (glutamate-cysteine ligase; EC 6.3.2.2) was isolated from an Escherichia coli strain enriched in the gene for this enzyme by recombinant DNA techniques. The purified enzyme has a specific activity of 1860 units/mg and a molecular weight of 56,000. Comparison of the E. coli enzyme with the well-characterized rat kidney enzyme showed that these enzymes have similar catalytic properties (apparent Km values, substrate specificities, turnover numbers). Both enzymes are feedback-inhibited by glutathione but not by gamma glutamyl-alpha-aminobutyrylglycine; the data indicate that glutathione binds not only at the glutamate binding site but also at a second site on the enzyme that interacts with the thiol moiety of glutathione but not with a methyl group. Both enzymes are inactivated by buthionine sulfoximine in the presence of ATP, suggesting a common gamma-glutamyl phosphate intermediate. However, unlike the rat kidney enzyme that has an active center thiol, the bacterial enzyme is insensitive to cystamine, gamma-methylene glutamate, and S-sulfo amino acids, indicating that it does not have an active site thiol. Thus, the rat kidney and E. coli enzymes share several catalytic features but differ in active site structure. If the active site thiol of the rat kidney enzyme is involved in catalysis, which seems likely, there would appear to be differences in the mechanisms of action of the two gamma-glutamylcysteine synthetases. PMID- 2895926 TI - Chromosomal organization of the cytochrome P450-2C gene family in the mouse: a locus associated with constitutive aryl hydrocarbon hydroxylase. AB - Cytochromes P-450 represent a superfamily of enzymes with a central role in the metabolism of drugs, chemical toxins, and carcinogens. We have used genetic analysis to establish the complexity and catalytic function of a recently identified constitutively expressed murine hepatic cytochrome P-450 encoded by P450-2C. Southern blotting analysis shows that there are at least seven or eight genes within this family in the mouse and rat and that DNA restriction fragment length variants between different mouse inbred strains are observed. Analysis of recombinant inbred strains derived from these parent strains shows (i) these genes are clustered within 1 centimorgan, (ii) this gene family does not correspond to any of the known cytochrome P-450 loci or map near any well characterized genomic markers, and (iii) this gene family segregates to within 1 2 centimorgans of a locus controlling constitutive aryl hydrocarbon hydroxylase activity in mice. With use of Chinese hamster/mouse somatic cell hybrids, the P450-2C locus was assigned to a region of mouse chromosome 19 that appears to be syntenic with the previously mapped human P450C2C locus on human chromosome 10. By in situ hybridization to mitotic mouse chromosomes, we have localized this region to the tip of chromosome 19. These results are discussed in relation to the physiological roles of this P-450 family in foreign compound metabolism and steroid oxidations. PMID- 2895927 TI - Use of synthetic oligonucleotides for genomic DNA dot hybridization to split the DQw3 haplotype. AB - Comparison of two different HLA-DQ beta gene sequences from two DR4 individuals, probably corresponding to DQw3.2 (DQR4) and DQw3.1 (DQR5) specificities, has shown several nucleotide variations. Eight oligonucleotides (24 bases long), derived from these polymorphic areas, have been synthesized. Each oligonucleotide was hybridized to BamHI-digested DNA samples from eight families with HLA-DR4 individuals. Four polymorphic BamHI fragments were detected. Two of eight oligonucleotides gave a single signal (8.9 kilobases) on DQw3.2-positive haplotypes. We used one of these oligonucleotides in a genomic DNA dot hybridization and detected a hybridization signal only in DQw3.2-positive individuals. A very simple test like this allows the screening of a large population sample within a very short period. PMID- 2895928 TI - High recombination between two physically close human basement membrane collagen genes at the distal end of chromosome 13q. AB - Two basement membrane collagen genes coding for the pro alpha 1 chain and pro alpha 2 chain of type IV collagen map to 13q34 and are linked with a maximum likelihood estimate of recombination of 0.028 at a logarithm of odds (lod) score of 19.98. The single-copy sequence that identifies the locus D13S3 is also closely linked to both collagen genes. Four enzymes reveal polymorphisms with COL4A1, and 10 haplotypes have been observed in Caucasoids. Within COL4A1 a nonrandom association of alleles exists only between alleles defined by Hae III and those defined by the other three enzymes. A random association of alleles of COL4A1 and COL4A2 is observed. Between the two collagen genes were detected three meiotic recombination events that contributed to the estimate of 2.8% recombination. This is higher than expected for two genes that lie within 650 kilobases of each other. The lack of linkage disequilibrium between COL4A1 and COL4A2 is in agreement with the relatively high recombination that is observed. PMID- 2895929 TI - Rapid desensitization of glutamate receptors in vertebrate central neurons. AB - We have examined glutamate receptor desensitization in voltage-clamped embryonic chicken spinal cord neurons and postnatal rat hippocampal neurons maintained in culture. Rapid currents that rose in 0.8-3.6 msec were evoked when glutamate was ionophoresed with 0.5- to 1.0-msec pulses. With prolonged pulses or brief, repetitive pulses, glutamate-evoked currents decayed rapidly in a manner that was independent of holding potential. A similar desensitization occurred following close-range pressure ejection of glutamate. The rapid, desensitizing glutamate current exhibited a linear current-voltage relation and it was not blocked by 2 amino-5-phosphonovalerate, suggesting that it was mediated by N-methyl-D aspartate-insensitive (G2) receptors. Desensitization of G2 receptors may be agonist-dependent: currents evoked by kainate, a selective G2 agonist, did not decay, whereas prior application of glutamate did reduce the size of kainate responses. The appearance of the rapid current depended critically on the position of the ionophoretic pipette. Such glutamate-receptor "hot spots" often corresponded to points of contact with neighboring neurites, which raises the possibility that they are located at synapses. PMID- 2895930 TI - Growth of Paracoccus denitrificans on [2,3-13C]succinate and [1,4-13C]succinate. III. Biosynthetic pathways. AB - The biosynthesis in vivo of a number of amino acids, sugars, and purines in Paracoccus denitrificans grown on either [2,3-13C]succinate or [1,4-13C]succinate was investigated by using gas chromatography-mass spectrometry. The distribution of label in the TCA-cycle-related amino acids indicated that carbon intermediates of energy metabolism were utilized as precursors for the biosynthesis of these amino acids in vivo. The biosynthesis of glycine, serine, phenylalanine and glycerol from labelled succinate in vivo were consistent with phosphoenol pyruvate as an intermediate. A mechanism for the formation of C4, C5 and C6 sugars without the use of fructose-1,6-bisphosphate aldolase (which has not been detected in P. denitrificans) is proposed. The 13C-enrichments of ribose in the bacterium indicate that there are at least three routes of ribose biosynthesis operating during growth on labelled succinate. The probability distribution of labelled purine molecules was successfully predicted for adenine, guanine and adenosine, thus confirming their generally accepted route of biosynthesis in vivo. PMID- 2895931 TI - The beta sector of the rabbit's dorsal lateral geniculate nucleus. AB - The beta sector of the rabbit's dorsal lateral geniculate nucleus is a small region of nerve cells scattered among the fibres of the geniculocortical pathway. In its topographical relations it resembles the perigeniculate nucleus of carnivores, which contains neurons driven by geniculate and visual cortical neurons and which sends inhibitory fibres back into the geniculate relay. We have traced retinogeniculate, geniculocortical and corticogeniculate pathways in rabbits by using horseradish peroxidase or radioactively labelled proline and have found that the beta sector resembles the perigeniculate nucleus in receiving no direct retinal afferents, sending no efferents to the visual cortex (V-I), and receiving afferents from the visual cortex. The corticogeniculate afferents are organized so that the visual field map in the beta sector and the main part of the lateral geniculate relays are aligned, as are the maps in the cat's perigeniculate nucleus and the main part of the geniculate relay of carnivores. Electron microscopical studies show similar types of axon terminals in the rabbit and the cat for the main part of the geniculate relay on the one hand and for the beta sector and the perigeniculate nucleus on the other. Earlier observations that the proportion of putative inhibitory terminals (F-type terminals) is lower in the rabbit's than the cat's geniculate region are confirmed. A major difference between the beta sector and the perigeniculate nucleus has been revealed by immunohistochemical staining for GABA. Whereas almost all of the cat's perigeniculate cells appear to be GABAergic, the proportion in the beta sector is much lower, and not significantly different from that found in the main part of the rabbit's geniculate relay. It is concluded that the beta sector shares many of the organizational features of the perigeniculate nucleus. A common developmental origin seems probable, but the functional differences remain to be explored. PMID- 2895932 TI - Tension reactivation and potentiation in guinea pig atrium: the effects of isoprenaline, calcium and rate changes. AB - The process of tension repriming and the phenomenon of tension potentiation after premature stimulation (post-extrasystolic potentiation, PESP) were studied in the adult guinea pig atrium. The following results were obtained. (i) Reducing extracellular calcium, [Ca]o, to 50% of normal did not significantly change the rate of tension repriming. However, in the presence of 5 microM isoprenaline (which greatly speeded up repriming) the same reduction in [Ca]o slowed down the repriming process. (ii) Increases in the rate of stimulation enhanced the rate of tension repriming in a control medium, but this rate-dependence was absent in the presence of isoprenaline. (iii) Isoprenaline (20 microM) abolished PESP. A reduction in [Ca]o or the addition of verapamil (still with isoprenaline) partly restored tension potentiation. In neonatal guinea pig atria, a large PESP was evident, which was only slightly reduced by isoprenaline. These results are interpreted as reflecting changes induced by isoprenaline in the degree of filling of sarcoplasmic reticulum (SR) stores with calcium, and in the rate of calcium recycling between uptake and release sites within the SR network. The large PESP found in the neonate, and its relative insensitivity to isoprenaline was interpreted as reflecting a scarcity of SR. This implies that tension potentiation may also reflect changes in sarcolemmal calcium currents. PMID- 2895933 TI - The spectral properties and photosensitivities of analogue photopigments regenerated with 10- and 14-substituted retinal analogues. AB - Analogues of 11-cis- and 9-cis-retinal with substitutions at positions 10 and 14 were used to regenerate analogue photopigments with two opsins: that of the transmuted (cone-like) 521-pigment of Gekko gekko and that of the rhodopsin of Porichthys notatus. The spectral absorbances and photosensitivities of the regenerated photopigments were determined and compared, first, between the two systems of analogue photopigments, and second, in the responses to the two opsins. Unlike the 10-fluoropigments, the comparable 14-compounds were significantly red-shifted by 19-30 nm and their sensitivity to light was similar to that of the parent 11-cis- and 9-cis-pigments. These were the results for both analogue pigments. In contrast, the 10-pigments were spectrally located close to the wavelengths of the parent compounds and the photosensitivity was significantly reduced, especially in the case of the 9-cis-analogues. Evidence was obtained for a steric hindrance effect at position 14, for no regeneration was obtained when methyl or ethyl groups were at this carbon. In the 10 substituted retinals, steric hindrance was noted only for the gecko; only the fluorosubstituted, but not the chloro-, the methyl- or the ethyl-substituted, retinals reacted. With the fish opsin, pigments were regenerated with all but the ethyl-substituted retinal. The gecko opsin appears to have a more restricted binding site. Another feature of the gecko was related to the chloride bathochromic and hyperchromic effects, in which the 521-pigment prepared in a chloride-deficient state has a blue-shifted spectrum compared with the spectrum obtained after the addition of chloride, and its extinction is raised by the addition of chloride to give a mean ratio of 1.23 for the two extinctions, one with, the other without, added chloride. The 11-cis-10-F-analogue pigment gave both chloride effects and the hyperchromic ratio was the same as that recorded for the native visual pigment. In contrast, the pigment formed with 11-cis-14-F retinal gave a hyperchromic ratio significantly greater than 1.23. A similar contrast in the responses to chloride was obtained with the analogue photopigments regenerated with the 9-cis-10-F- and 9-cis-14-F-chromophores. This difference between the two systems is interpreted as the result of a specific configurational feature of the gecko opsin when in the chloride-deficient state that is relevant to the binding of the retinal analogue.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2895934 TI - The organization of corticocortical projections from area 17 to area 18 of the cat's visual cortex. AB - Retrogradely transported tracers were injected into area 18 of the visual cortex of the adult cat to study the organization of corticocortical projections from area 17 to area 18. All injections, whether very small or relatively large, and irrespective of their exact location in area 18, produced a discontinuous, clustered distribution of labelled cells, mainly in layers II, III and upper IV, in a topographically related region of area 17. The mean centre-centre distance between neighbouring patches was about 750 microns. We conclude that the overall population of cells projecting to area 18 is genuinely distributed in a patchy fashion and that they provide an efficient spatial sample of information from area 17. Comparison of the dimensions of each injection site and of the retrogradely labelled territory suggested that each region in area 18 receives a convergent input from a zone in area 17 whose visual field representation is about 0.8 M-1 deg larger in all directions (where M is the magnification factor in millimetres per degree at the termination site in area 18). Pairs of injection were made in area 18 by placing small volumes of two fluorescent tracers, fast blue and diamidino yellow, side-by-side in either a rostrocaudal or a mediolateral plane, with different distances between them. When the boundaries of the dense central cores of two injection sites were separated, at their closest points, by about 1.6 mm, the two corresponding distributions of labelled cells in area 17 were just non-overlapping, suggesting that each group of cells in area 17 sends a divergent projection in innervate a zone about 0.8 mm larger in all directions in area 18. More closely spaced injections led to overlap of the distributions of labelling by the two dyes, with shared clusters containing a mixture of labelled cells. The proportion of double-labelled cells in these shared clusters never exceeded 4.4% (but was 70% after sequential injection of the two dyes at a single point). We conclude that, although each cluster of cells sends a divergent projection to area 18, the majority of individual axons terminate more discretely, perhaps providing specific inter-connections between functionally corresponding 'columns' in the two areas. PMID- 2895935 TI - Managing anxiety. PMID- 2895936 TI - Comparative study of the pharmacokinetics of zuclopenthixol decanoate and fluphenazine decanoate. AB - Seventeen outpatients were treated with depot neuroleptics, zuclopenthixol decanoate in Viscoleo or fluphenazine decanoate in sesame oil, with dosage intervals of 3 weeks. During the 4th, 6th, and 8th dosage interval blood samples were drawn in oxalated tubes. Plasma concentrations of the active neuroleptic drugs, zuclopenthixol and fluphenazine, were determined by high performance liquid chromatography. The concentrations indicated some interindividual as well as intraindividual variations. For zuclopenthixol the maximum concentration was most often seen at day 7 after injection, whereas the kinetics of the fluphenazine concentrations was more variable. There was an indication of more fluctuation in the 4th dosage interval than in the 8th dosage interval, possibly due to the fact that steady state has not yet been achieved at the 4th dosage interval. PMID- 2895937 TI - GABA agonists in cebus monkeys with neuroleptic-induced persistent dyskinesias. AB - Tetrahydroisoxazolopyridinol (THIP), a GABA receptor agonist, gamma-acetylenic GABA(GAG) and gamma-vinyl-GABA(GVG), two GABA transaminase inhibitors were given in single parenteral doses to three Cebus apella monkeys with persistent dyskinetic movements induced by earlier long-term administration of haloperidol. High doses of THIP temporarily abolished dyskinesias but also caused bradykinesia, ataxia, dystonia and myoclonic jerks. GAG and GVG reduced dyskinesias to a lesser extent and with fewer side effects. Whether the observed antidyskinetic effect is secondary to the concomitant general toxic effects or if these drugs have a specific antidyskinetic action remains an open question. PMID- 2895938 TI - Further studies on the interaction between bromocriptine and SKF38393 in reserpine and alpha methyl-para-tyrosine-treated mice. AB - In a previous report, we showed that the relatively selective dopamine (DA) D-2 agonist bromocriptine (BRC), when combined with the selective D-1 agonist SKF38393, produced in DA-depleted mice a marked locomotor stimulation, despite BRC and SKF38393 being inactive by themselves (Jackson and Hashizume 1986). The present series of experiments was designed to further explore this interaction. In all experiments, mice were pretreated with reserpine and/or alpha methyl-p tyrosine (AMPT). In mice pretreated with reserpine, AMPT or reserpine plus AMPT, BRC plus SKF38393 produced marked excitation whether the BRC was given 3 or 1 h prior to the SKF38393 challenge. However, while there was no absolute requirement that BRC be given a certain time before SKF38393, this factor was of some importance, with the onset of locomotor stimulation produced by the combination being much more rapid if the BRC was given 3 h rather than 1 h before the SKF38393. Interestingly, the degree of locomotor stimulation produced by the combination was always greatest in the animals premedicated with reserpine alone. If AMPT was also used (with or without reserpine), the stimulation produced by the combination was reduced, which may have resulted in part from a non-specific depressant effect of the AMPT. From these results, it seems as though endogenous DA is not required for BRC to work, provided that D-1 receptors are stimulated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2895939 TI - Differential sensitivity of opioid-induced feeding to naloxone and naloxonazine. AB - The high-affinity mu-1 opioid binding site has been implicated in some opioid responses (e.g., supraspinal analgesia) but not others (e.g., respiratory depression) by comparing the actions of naloxone, a short-acting, non-selective antagonist, and naloxonazine, an irreversible and selective mu-1 antagonist. The mu-1 site has been implicated in the opioid component modulating free feeding and deprivation-induced feeding, but not glucoprivic feeding. The present study compared naloxone and naloxonazine antagonism of hyperphagia induced by morphine, ethylketocyclazocine (EKC), dynorphin and d-ala2,d-leu5-enkephalin (DADL) in rats. Morphine produced a dose-dependent (0.01-5 mg/kg) hyperphagia in mildly food-deprived rats that was blocked by naloxone (0.01-10 mg/kg). Naloxonazine (10 mg/kg) shifted the morphine hyperphagia dose-response curve to the right. These effects could not be fully accounted for by the intrinsic hypophagic properties of these antagonists. EKC produced a dose-dependent (0.5-5 mg/kg) hyperphagia which was blocked by naloxone (10 mg/kg) only at low effective EKC doses. Naloxonazine (10 mg/kg) failed to affect EKC hyperphagia. Naloxone, but not naloxonazine also blocked dynorphin and DADL hyperphagia. These results indicate that feeding induced by opiate and opioid agonists are differentially mediated by the mu-1 and other opioid binding sites; these data contrast with the modulation by the mu-1 site of the supraspinal analgesia induced by each of these agonists. PMID- 2895940 TI - Differential effects of opioid and nonopioid analgesics on conditional discriminations in pigeons. AB - Under the fixed-consecutive-number schedule (FCN), pigeons were reinforced for responding eight or more times on one response key (work key), and then responding once on a second response key. In one component of this schedule, an external stimulus signalled the completion of the response requirement on the work key (FCN 8-SD), whereas no stimulus change was programmed under the other (FCN 8). Across a range of doses, the mu opioid agonist morphine, the kappa opioid agonist U50,488 and the opioid antagonist naloxone had no consistent effect on accuracy under either FCN schedule. Naloxone and accuracy under either FCN schedule. Naloxone and U50,488 produced a general flattening of the conditional probability functions by decreasing the conditional probability of response runs exceeding the minimum response requirement of eight consecutive responses on the work key. The sigma agonists phencyclidine and (+)N allylnormetazocine and the nonopioid analgesics clonidine and l-nantradol produced large decreases in accuracy under the FCN 8 and small decreases under the FCN 8-SD. With the exception of (+)N-allylnormetazocine, these drugs consistently increased the conditional probability of responses runs shorter than the minimum response requirement on the work key. These findings indicate that the accuracy-altering effects of some opioid and nonopioid analgesics depend in part on the type of discrimination task. PMID- 2895941 TI - Dose-response effects of 8-cyclopropyltheophylline on sleep and wakefulness in rats. AB - The dose-response effects of the substituted xanthine 8-cyclopropyltheophylline (CPRT) on sleep and wakefulness (W) after intraperitoneal administration to rats were examined by means of simultaneous electroencephalographic (EEG) and electromyographic (EMG) recordings. Doses of 20 and 40 mg/kg CPRT increased W and decreased slow wave sleep (SWS) in rats, indicating CNS stimulant effects. The greatest CNS stimulation was produced by the lowest (20 mg/kg) dose of CPRT examined, which also increased the latency to SWS. In addition, the 20 mg/kg dose of CPRT also significantly decreased the amount of total sleep (TS), as compared to the vehicle group, during all time periods examined. In contrast, the 80 mg/kg dose of CPRT decreased W and increased both SWS and TS. However, this apparent hypnotic effect of the 80 mg/kg CPRT may be due to toxicity, since 80% of rats treated with this dose of the drug died within 48 h of injection. PMID- 2895942 TI - [Primary prevention of coronary disease. III. Report from the working conference of the World Health Organization, Anacapri, 15-19 October 1984]. PMID- 2895943 TI - The effect of H2-antagonists on the absorption of bupropion in rats. AB - Bupropion absorption was investigated by oral administration of bupropion alone or in combination with cimetidine or ranitidine to rats. Blood samples were collected before and at 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.5 and 6 h after bupropion administration. The assay of bupropion in plasma was carried out by an HPLC method. Cimetidine or ranitidine did not significantly affect the plasma bupropion concentrations on concurrent administration. No significant differences were observed between area under the curves (AUC)s, maximum plasma concentration, time to peak and the half-life of bupropion among the three groups. These results indicate that neither cimetidine nor ranitidine significantly affects the rate or the extent of bupropion absorption in rats. PMID- 2895944 TI - [Medical treatment of gastric and duodenal ulcers: reality, illusions and hopes 1987]. PMID- 2895945 TI - [A new strategy in the diagnosis of digestive cancer]. PMID- 2895946 TI - [Digestive tract involvement in collagenoses]. PMID- 2895947 TI - [Usefulness of biological tests in diagnosing alcoholic liver diseases]. PMID- 2895948 TI - [Intestinal angiodysplasia]. PMID- 2895949 TI - [Comparative evaluation of ultrasonography and radiologic examination in diagnosing biliary lithiasis]. PMID- 2895950 TI - [Echographic volumetry of the gallbladder in biliary dyskinesia]. PMID- 2895951 TI - [Hepatorenal syndrome. Its clinical, paraclinical, therapeutic, evolutive and prognostic aspects]. PMID- 2895952 TI - GABA distribution in a pain-modulating zone of trigeminal subnucleus interpolaris. AB - A recent model for control of spinal and medullary nociceptive neurons (Basbaum and Fields, 1984) incorporates a gamma-aminobutyric acid-ergic (GABA-ergic) cell into this circuitry and indicates that such elements could act as one substrate for presynaptic inhibition of primary afferents. This concept is supported by a variety of pharmacological and electrophysiological studies. We therefore examined the distribution of GABA-ergic activity in trigeminal subnucleus interpolaris (Vi) by focusing on the types of cells, together with dendritic and synaptic profiles, that are immunocytochemically labeled with an antiserum against glutamic acid decarboxylase (GAD). GAD occurred throughout Vi but was most concentrated in the ventrolateral quadrant and interstitial nucleus. It was localized to groups of small neurons with two to three primary dendrites, and within numerous punctate profiles suggestive of synaptic elements. Electron microscopy revealed labeled dendrites, some of which were postsynaptic to scalloped terminals of presumptive primary afferents. Other labeled dendritic elements, which were quite variable in size, engaged both GAD-labeled and unlabeled synapses. Most GAD synapses displayed clear round vesicles and formed contacts with unlabeled perikarya and a variety of dendritic processes. Numerous GAD-positive synapses were also incorporated into axoaxonic clusters, in which the GAD element was presynaptic to scalloped terminals. Others engaged in serial arrays with other unlabeled terminals, which, in turn, were presynaptic to dendrites. Occasionally, GAD synapses formed contacts with GAD-positive dendrites. These data show that GABA is localized to a variety of neuronal elements in ventrolateral Vi and the interstitial nucleus. These occur in spatial arrangements providing an anatomical substrate for postsynaptic modulation of activity in this area. GABA terminals also appear to be involved in a presynaptic inhibitory mechanism, which may, in some instances, affect transmission in primary afferents. PMID- 2895954 TI - [The current role of beta-blockers in arterial hypertension]. PMID- 2895953 TI - [The beta-adrenergic receptor and its physiology]. PMID- 2895955 TI - [The current role of beta-blockers in coronary insufficiency]. PMID- 2895956 TI - [Heart failure: beta-stimulant or beta-blocker?]. PMID- 2895957 TI - [Beta-stimulants in pneumology]. PMID- 2895958 TI - [Beta-mimetic drugs in obstetrics]. PMID- 2895959 TI - [The treatment of rheumatoid polyarthritis using salazosulfapyridine (Salazopyrine). A 6-month open study of 34 patients]. PMID- 2895961 TI - Baltimore's "fiery blast". PMID- 2895960 TI - Age and sex differences in cardiovascular reactivity to adrenergic agonists, mental stress and isometric exercise in normal subjects. AB - Dose-response curves for intravenous bolus injections of isoprenaline were carried out in 40 normal subjects, in four groups of 10 comprising young and middle-aged males and females. The isoprenaline dose required to raise the heart rate by 50 beats/min, the CD50 (chronotropic dose 50 beats/min), was calculated individually and taken as a measure of the beta-adrenergic responsiveness. Females had significantly higher sensitivity to isoprenaline than males, i.e. lower CD50 values (95% confidence interval 0.07-0.11 versus 0.12-0.17 micrograms/kg body weight, p less than 0.001), and young subjects had higher sensitivity than middle-aged subjects (95% confidence interval for CD50 0.07-0.10 versus 0.12-0.18 microgram/kg body weight, p less than 0.001). Dose-response curves were also carried out for intravenous prenalterol, a partial beta 1 adrenergic agonist. The maximal heart-rate response to prenalterol (delta HRP) showed a significant inverse linear relationship with the CD50 (delta HRP = 44.8 0.11 x CD50, r = -0.53, rs = -0.69, p less than 0.001). A mental stress programme and isometric exercise gave significant increases in heart rate and blood pressure for all groups, but there was no significant relationship between the CD50 and the heart-rate response. By applying a theoretical model, developed by Kenakin and Beek [13], to the isoprenaline-prenalterol data, it is suggested that the observed age and sex differences in beta-adrenergic responsiveness are caused by a tissue-related difference in the stimulus-response mechanism. PMID- 2895962 TI - [The alcoholism perspective in primary health care. The 1st S. Joao de Deus Mental Health Meeting for Nurses, Coimbra, March 1987]. PMID- 2895963 TI - Effects of HOE 760 (histamine H2-receptor antagonist) on diazepam pharmacokinetics. AB - A double-blind cross-over study of the effects of HOE 760 (histamine H2-receptor blocker) on diazepam pharmacokinetics was conducted in 12 healthy men. HOE 760 or placebo was given daily for 12 days and, after a wash-out period of 9 days, the alternate medication was given for 12 days. Diazepam 10 mg was given intravenously on day 6 of each of the 12-day periods. Blood was taken up to 1 week after the diazepam injections for assay of diazepam and desmethyldiazepam. The co-administration of HOE 760 did not affect the pharmacokinetics of diazepam and desmethyldiazepam. PMID- 2895964 TI - Isolation of human T-lymphotropic virus type I (HTLV-I) from a black South African with Kaposi's sarcoma. AB - Serological evidence for HTLV-I infection in the South African population has now been confirmed by the isolation of the virus from the peripheral blood lymphocytes of an adult Tsonga male. The subject was an indigenous black man from the south-eastern Transvaal who had suffered from Kaposi's sarcoma for a decade and in whom serum antibodies against HTLV-I were demonstrated. T-lymphocyte cell lines were established from his peripheral blood lymphocytes and shown to be productively infected with HTLV-I as evidenced by: the characteristic cell morphology; the typical viral morphogenesis on ultra-thin section electron microscopy; the viral genome in DNA extracted from the cell lines; characteristic reverse transcriptase activity and viral specific proteins in the cell culture supernatant fluids. Spread of infection occurs through sexual intercourse, from mother to child, and by blood transfusion. Donated blood should be screened to contain the spread of HTLV-I infection. PMID- 2895965 TI - [Interrelations of the endocrine glands and regulatory gastrointestinal peptides]. PMID- 2895966 TI - [Comparison of the effects of loprazolam and alcohol on psychomotor performance and memory in healthy subjects]. PMID- 2895967 TI - Early changes in bile duct lining cells and hepatocytes in rats treated with alpha-naphthylisothiocyanate. AB - Morphological changes in bile duct lining cells precede morphological changes in hepatocytes in rats treated with 300 mg/kg body wt of alpha naphthylisothiocyanate (ANIT). Four hours after dosing, electron microscopy showed dilation of bile ducts, loss of microvilli from bile duct epithelial cells, and an apparent opening of the tight junctions between some bile duct epithelial cells. These changes were more pronounced after 6 hr and there was in some bile duct lining cells detachment of the nuclear membrane and vacuolation of the endoplasmic reticulum. Light microscopy 6 hr after treatment with ANIT showed some portal edema and loss of gamma-glutamyl transpeptidase activity from the bile duct lining cells. By 8 hr after treatment many ducts showed clear-cut damage, with bile plugs forming and cells exfoliating into the ducts. Twenty-four hours after treatment the majority of bile ducts were destroyed but by 48 hr there was some evidence of regeneration. No tissue changes were seen at the light microscopy level in the liver parenchymal cells 4, 6, or 8 hr after treatment. At the ultrastructural level some alterations in the tight junctions between hepatocytes were seen 6 hr after treatment. No other changes were observed before this time point. By 24 hr after treatment there was focal necrosis in the parenchyma. Assay of gamma-glutamyl transpeptidase and albumin in bile gave results consistent with the histochemical evidence for the loss of activity from bile duct lining cells and for weakening of the tight junctions between hepatocytes. PMID- 2895968 TI - A comparison of serial E-RFC monitoring and immunomagnetic quantitation of CD2+ cells in RATG-treated transplant recipients. PMID- 2895969 TI - T11+/DR+ lymphocytes in renal allograft recipients with irreversible rejection. PMID- 2895970 TI - Sensitivity of newly transplanted marrow to further irradiation. PMID- 2895971 TI - Remote intramuscular injection of immobilising drugs into fish using a laser aimed underwater dart gun. AB - Sixty coldwater and warmwater fish ranging in weight from 2 to 35 kg were injected intramuscularly with the hypnotics alphaxalone-alphadolone and metomidate hydrochloride and the non-depolarising muscle relaxant gallamine triethiodide using a laser-aimed underwater dart gun. Alphaxalone-alphadolone produced sufficient sedation for easy netting within five to 20 minutes at doses between 0.3 and 0.5 ml/kg, with induction being somewhat faster in warmwater species. The pattern of induction was similar with metomidate but required doses of 40 to 60 mg/kg. The muscle relaxant gallamine triethiodide showed promise as a practical agent for the capture and handling of large fish by virtue of its smooth induction of paralysis at doses between 1 and 3 mg/kg and its reversible supplementation with orally administered metomidate hydrochloride. PMID- 2895972 TI - Accumulation of gamma-aminobutyric acid by horizontal cells isolated from the goldfish retina. AB - In the goldfish retina, H1 horizontal cells, which receive input predominantly from red sensitive cone photoreceptors, possess a single high-affinity uptake mechanism for gamma-aminobutyric acid (GABA). This GABA uptake is enhanced by light stimulation, which hyperpolarizes the H1 cells. The regulation of this uptake mechanism was examined in isolated horizontal cells by measuring the accumulation of exogenously supplied 3H-GABA. Solutions containing elevated external K+ or glutamate were used to quantitatively depolarize the cells to reveal that the potential-sensitive GABA uptake is maximal under hyperpolarizing conditions and minimal with depolarization. The driving force for GABA uptake is derived from the Na+ electrochemical gradient, with approximately 2 Na+ ions being cotransported with each molecule of GABA. The results presented suggest that the uptake mechanism permits the synaptic concentration of GABA to be regulated by the membrane potential of the H1 horizontal cells. This, then permits the presynaptic horizontal cell to modulate the synaptic concentration of transmitter in this tonically active synapse. PMID- 2895973 TI - [Facial injuries in childhood. Etiology, location, therapy]. PMID- 2895975 TI - Turbinate atrophy in mice caused by Bordetella pertussis. PMID- 2895974 TI - Conversion of ammonia to glutamate by L-glutamic dehydrogenase, alcohol dehydrogenase and NAD+ immobilized within lipid-polyamide polyethyleneimine microcapsules. PMID- 2895976 TI - Mammogram interpretation by physician assistants. PMID- 2895977 TI - Flow cytometric DNA and nuclear antigen content in astrocytic neoplasms. AB - Simultaneous flow cytometric DNA content and proliferation-associated nuclear antigen (p105) quantitation was performed on 23 astrocytic tumors and the results correlated with histologic subtype. Three of nine anaplastic astrocytomas and one of ten glioblastomas had an identifiable aneuploid peak, while all four well differentiated astrocytomas were diploid. Cell cycle analysis of malignant gliomas revealed a higher mean percentage of S and G2M cells compared to well differentiated astrocytomas but there was considerable overlap between histologic subtypes. Nuclear antigen analysis of diploid tumors showed a higher mean p105 fluorescence of S + G2M cells than G0G1 cells from the same case but there were no apparent differences in p105 expression by histologic subtype. Aneuploid tumors showed enhanced expression of p105 relative to diploid cells. The findings suggest that the aggressive course of high grade glial tumors may be related to an abnormal DNA stemline or an increase in proliferative activity. PMID- 2895978 TI - Use of narcotics in sickle cell disease. PMID- 2895979 TI - Cryptorchism, orchiopexy, and the risk of testicular cancer. AB - Adult white male residents of 13 counties of western Washington State in whom germ cell testicular cancer was diagnosed between 1977 and 1983 (n = 333) were interviewed by telephone regarding their history of cryptorchism and its treatment. The same interview was given to a sample of 675 men selected from the population of these counties by dialing telephone numbers at random. Men who reported a history of cryptorchism were 5.9 times (95 per cent confidence interval 3.4-10.2) more likely than men without such a history to develop testicular cancer. Compared with noncryptorchid men, those with unilateral cryptorchism were at greater risk of developing a tumor on the side of nondescent (relative risk = 8.0) than on the opposite side (relative risk = 1.6). The size of the increased risk tended to be smaller among cryptorchid men who had undergone orchiopexy by age 10 than for other cryptorchid men, but the influence of orchiopexy in early childhood could not be evaluated in this population. These observations offer support for the hypothesis that one or more local factors (e.g., temperature elevation) account for the major part of the increased risk of germ cell testicular tumors in cryptorchid men. PMID- 2895981 TI - An extensive search for RFLP in the human glucose-6-phosphate dehydrogenase locus has revealed a silent mutation in the coding sequence. AB - The genetic polymorphism of an approximately 100-kb DNA region comprising and flanking the glucose-6-phosphate dehydrogenase (G6PD) gene on human chromosome Xq28 has been analyzed in detail. By using 14 unique sequence probes and 18 restriction enzymes, we have characterized 257 restriction fragments or 370 restriction sites. On testing 12-57 individual X chromosomes, all sites but one were nonpolymorphic. However, a PstI site that maps to exon 10 of the G6PD gene, which is still monomorphic in all British and Italian subjects tested, is polymorphic in west-African people. Specifically, it is absent from 22% of Nigerian X chromosomes. By sequence analysis we have shown that the absence of this PstI site results from a G----A replacement at position 1116, corresponding to the third base of a glutamine codon; no amino acid change is produced in the protein. Thus, a polymorphic silent mutation is demonstrated in a human gene. PMID- 2895980 TI - Haplotypes of the coagulation factor XIII A subunit locus in normal and deficient subjects. AB - Several RFLPs have been detected using a cDNA fragment encoding the amino terminal half of the A subunit of factor XIII. The RFLPs show little linkage disequilibrium and form many different haplotypes that can be used to identify chromosomes transmitting factor XIII A subunit deficiency. Southern blot analysis of three deficient individuals from two families showed that, in these cases, factor XIII A subunit deficiency did not result from a major gene deletion or rearrangement. Factor XIII A subunit deficiency was found to be associated with three different haplotypes, suggesting heterogeneity in the mutations causing this disorder. PMID- 2895982 TI - Tightly linked flanking markers for the Lowe oculocerebrorenal syndrome, with application to carrier assessment. AB - The Lowe oculocerebrorenal syndrome (OCRL) is characterized by congenital cataract, mental retardation, and defective renal tubular function. A map assignment of OCRL to Xq24-q26 has been made previously by linkage analysis with DXS42 at Xq24-q26 (theta = 0, z = 5.09) and with DXS10 at Xq26 (theta = 0, z = 6.45). Two additional families were studied and three additional polymorphisms were identified at DXS42 by using a 35-kb sequence isolated with the probe detecting the original polymorphism at DXS42. With additional OCRL families made informative for DXS42, theta remained 0 with z = 6.63; and for DXS10 theta = 0.03 and z = 7.07. Evidence for placing OCRL at Xq25 also comes from a female with Lowe syndrome and an X;3 translocation. We have used the Xq25 breakpoint in this patient to determine the position of OCRL relative to the two linked markers. Each derivative chromosome was isolated away from its normal counterpart in somatic cell hybrids. DXS42 was mapped to the derivative chromosome X containing Xpterq25, and DXS10 was mapped to the derivative chromosome 3 containing Xq25 qter. The markers DXS10 and DXS42 therefore show tight linkage with OCRL in six families and flank the Xq25 breakpoint in a female patient with an X;3 translocation. Linkage analysis with flanking markers was used to assess OCRL carrier status in women at risk. Results, when compared with carrier determination by ophthalmologic examination, indicated that the slit-lamp exam can be a sensitive and specific method of carrier determination in many cases. PMID- 2895984 TI - Use of laboratory tests to monitor heavy drinking by alcoholic men discharged from a treatment program. AB - Changes in blood test values from the time of discharge from an alcohol treatment program to 3-month follow-up were studied in two consecutive series of alcoholic men. The parallel combination of a percent increase in gamma-glutamyltransferase (GGT) of greater than or equal to 20%, in aspartate aminotransferase (SGOT) of greater than or equal to 40%, and in alanine aminotransferase (SGPT) of greater than or equal to 20% over discharge values was developed as a rule and then cross validated to identify those alcoholic men who had resumed drinking at follow-up. Serial determination of these three test values in combination can be used to distinguish recovering alcoholics who remain abstinent from those who resume drinking. PMID- 2895985 TI - Tardive dyskinesia in bipolar affective disorder: aging, cognitive dysfunction, course of illness, and exposure to neuroleptics and lithium. AB - Cognitive function, course of illness, and medication history were assessed in 42 bipolar patients evaluated for the presence of involuntary movements. Among the 25 patients 55 years old or older, the 16 with involuntary movements were not distinguished from the nine without involuntary movements by past or current exposure to neuroleptics, anticholinergics, or carbamazepine, but they showed poorer cognitive function, had fewer major depressive episodes, and had received briefer exposure to lithium. The association between involuntary movements and cognitive dysfunction parallels that found in schizophrenia, suggesting that similar neurological processes may contribute to vulnerability to involuntary movements in the major functional psychoses. PMID- 2895983 TI - Chromosome I linkage studies in Charcot-Marie-Tooth neuropathy type I. AB - Charcot-Marie-Tooth neuropathy type 1 (CMT1) is an autosomal dominant disorder of peripheral nerve. The gene for CMT1 was originally localized to chromosome 1 by linkage to the Duffy blood group, but it has since been shown that not all CMT1 pedigrees show this linkage. We report here the results of linkage studies using five chromosome 1 markers--Duffy (Fy), antithrombin III (AT3), renin (REN), beta nerve growth factor (NGFB), and salivary amylase (AMY1)--in 16 CMT1 pedigrees. The total lod scores exclude close linkage of CMT1 to any of these markers. However, individual families show probable linkage of CMT1 to Duffy, AT3, and/or AMY1. No linkage was indicated with REN or NGFB. These results indicate the possible location of a CMT1 gene between the AMY1 and AT3 loci at p21 and q23, respectively, on chromosome 1 and support the theory that there is at least one other CMT1 gene. PMID- 2895986 TI - Hypothalamic pathology in the neuroleptic malignant syndrome. AB - The pathogenesis of the neuroleptic malignant syndrome is currently unclear, and no specific morphological abnormalities in the CNS of victims of neuroleptic malignant syndrome have been described. The authors report a case of neuroleptic malignant syndrome with recent foci of necrosis in the anterior and lateral hypothalamic nuclei. They discuss the role of tricyclic antidepressants, monoamine oxidase inhibitors, and neuroleptics in the development of this syndrome. They conclude that although the pathogenesis of the neuroleptic malignant syndrome is still not clear, necrosis of the hypothalamic nuclei may be pathognomonic for this syndrome. PMID- 2895987 TI - Subtle and underrecognized side effects of neuroleptic treatment in children with Tourette's disorder. AB - A variety of side effects developed in children treated with neuroleptics for Tourette's disorder. Of 208 children, 34 manifested dose-related symptoms of dysphoria, nine experienced a worsening of symptoms of Tourette's disorder that was attributed to akathisia, five became hostile and aggressive, three developed "fog states" that disappeared with discontinuation of neuroleptics or treatment with primidone, and three experienced symptoms of tardive dyskinesia that resolved with time. This data base of neuroleptic-treated children with Tourette's disorder demonstrates a variety of subtle and underrecognized side effects that may not be as readily discernible in children receiving neuroleptics for a primary psychiatric disorder. PMID- 2895988 TI - [Premedication and ambulatory anesthesia]. PMID- 2895989 TI - Differential-pulse adsorptive stripping voltammetry of the psychotropic drugs triazolam and clotiazepam. PMID- 2895990 TI - A multicenter, open study of the non-sedating antihistamine, terfenadine (Seldane), in the maintenance therapy of seasonal allergic rhinitis. AB - A multicenter open study was conducted throughout the 1984 fall pollen season to assess the possible development of tolerance or loss of efficacy to terfenadine in the maintenance therapy of patients with seasonal pollinosis. Patients with proven allergic pollinosis were entered into a 1-week initial treatment period taking terfenadine 60 mg bid and only those who responded to the initial treatment with "moderate" to "complete" relief continued on terfenadine throughout a 4 to 11-week pollen season for evaluation of continued efficacy. A total of 179 patients from five study centers were enrolled in the initial treatment period and 154 (86%) responded to terfenadine with "moderate" to "complete" relief of symptoms. Of these 154 patients who continued terfenadine treatment, approximately 90% of the patients maintained the same degree of relief throughout the pollen season. All symptoms of seasonal pollinosis including nasal congestion improved significantly the first day of treatment. This improvement in symptoms continued during the first week and remained unabated throughout the pollen season. The incidence of adverse events was low with sedation being reported by only 2.8% of patients at some time point during the study. It is concluded that terfenadine is a safe and effective non-sedating antihistamine in the maintenance therapy of seasonal allergic pollinosis and that tolerance is not noted during continued administration. PMID- 2895991 TI - Somatostatin treatment for cryptosporidial diarrhea in a patient with the acquired immunodeficiency syndrome (AIDS). PMID- 2895992 TI - Inhibition of nucleic acid synthesis in P-388 lymphocytic leukemia cells in culture by sesquiterpene lactones. AB - Helenalin and bis (helenalinyl) malonate, sesquiterpene lactones, were shown to be cytotoxic against the growth of P-388 lymphocytic leukemia cells in culture. DNA and protein synthesis were reduced by these agents preferentially, with RNA synthesis being affected only marginally. This study focused on the identification of the enzyme target(s) responsible for the inhibition of DNA synthesis by the sesquiterpene lactones. Purine synthesis was strongly inhibited at the IMP dehydrogenase step. Suppression of IMP dehydrogenase activity and purine synthesis paralleled the DNA synthesis inhibition with respect to both dose dependence and time of incubation with drug. Deoxyribonucleoside triphosphate pools in the P-388 cells were significantly reduced by both drugs and the DNA polymerase alpha activity was only moderately inhibited by both drugs in cytoplasmic preparation. However, inhibition of a partially purified DNA polymerase alpha was of a much greater magnitude. Activity of the ribonucleotide reductase complex was reduced by more than 50% at 100 microM concentration of either drug. The drugs appeared to affect the hydrogen donor system of the reductase complex, since the activity of the ribonucleotide reductase enzyme itself was not affected but both thioredoxin and glutaredoxin were markedly inactivated by the sesquiterpene lactones. Thymidylate synthetase activity was not affected by the sesquiterpene lactones in P-388 cells. These data suggest that the inhibition of IMP dehydrogenase and the ribonucleotide reductase complex activities by helenalin and bis (helenalinyl) melonate was the primary reason for the observed inhibition of DNA synthesis, but that inhibition of DNA polymerase alpha may also play a role. The inhibition of the sensitive enzymes is likely to be related to drug alkylation of thiol active groups of the enzymes in a manner similar to the action of N-ethylmaleimide. The mode of action of helenalin and bis (helenalinyl) malonate does not appear to be similar to that of the parthenolide-type sesquiterpene lactones which contain an epoxide moiety. PMID- 2895993 TI - Long-term treatment of anxiety and risk of withdrawal. Prospective comparison of clorazepate and buspirone. AB - Risk of withdrawal was investigated in a prospective, double-blind comparison of clorazepate dipotassium, a benzodiazepine with a long half-life, and the nonbenzodiazepine buspirone hydrochloride in the long-term treatment of anxious outpatients. Patients were treated with therapeutic doses of clorazepate dipotassium (15 to 60 mg/d) or buspirone hydrochloride (10 to 40 mg/d) for six continuous months before their tranquilizer therapy was blindly and abruptly stopped. There was a significant increase in symptom severity consistent with a withdrawal reaction for the clorazepate group but not the buspirone group. For the clorazepate group, there was a suggestion that previous discontinuous exposure to benzodiazepines might sensitize patients to subsequent withdrawal effects. For the buspirone group, a higher dropout rate raised questions about patient satisfaction with therapy in this rather chronically anxious population. PMID- 2895994 TI - The effect of vitamin E treatment on the incidence of OKT+4 lymphocytes in the peripheral blood of children with chronic respiratory tract infections. AB - Children with respiratory tract infections treated for 6 weeks with vitamin E improved their clinical status and normalized the proportion of OKT+4 T lymphocytes and the ratio of OKT+4 to OKT+8 cells in their peripheral blood. PMID- 2895995 TI - Effect of beta-adrenergic blockade on the growth rate of abdominal aortic aneurysms. AB - We retrospectively identified 136 patients with abdominal aortic aneurysms (AAAs) who were initially evaluated as outpatients. Twenty-seven of these patients met the following criteria for eligibility in the study: (1) roentgenographic documentation of an AAA larger than 3 cm, (2) at least two serial ultrasound size determinations over a minimum six-month interval, and (3) a documented medication history. Of these 27 patients, 12 received long-term beta-blockade, while 15 received no beta-blockade. The two groups were comparable with respect to age, sex, initial aneurysm size, mean systolic and diastolic blood pressure, and duration of follow-up (mean, 34 months). Among patients with beta-blockade, the mean growth rate was 0.17 cm/y. The rate for the controls was 0.44 cm/y. One patient of 12 (8%) in the beta-blocker group had a rate that exceeded the mean for the overall group compared with eight patients of 15 (53%) in the group with no beta-blockade. This difference was statistically significant. Thus, beta blockade may be associated with a decreased AAA growth rate in this small, retrospective study. PMID- 2895996 TI - Running injuries--knees to toes. PMID- 2895997 TI - Demonstration of a recent mutation in a family with isolated hemophilia A. PMID- 2895998 TI - Molecular characterization of meiotic recombination within the major histocompatibility complex of the mouse: mapping of crossover sites within the I region. AB - The molecular analysis of crossing-over within the mouse major histocompatibility complex provides a useful approach for the study of the structural characteristics of meiotic recombination. In this study five intra-I-region recombinants, each derived from Ik/Ib heterozygotes, were characterized for restriction-fragment length polymorphisms (RFLPs) characteristic of the I region of the two parental strains. Southern blot analysis of intra-I recombinant strains A.TBR2, A.TBR3, A.TBR5, A.TBR13, and A.TBR17 using six I-region DNA probes revealed that the point of crossing-over in all five recombinants occurred within a 6.2-kb KpnI-EcoRI segment located within the E beta gene. The segments of DNA containing the crossover point from each of the recombinant chromosomes were cloned by screening partial genomic libraries constructed in lambda gt7 bacteriophage. Construction of partial restriction maps of the cloned segments from the parental and recombinant chromosomes permitted the boundaries of the area containing the crossover site to be narrowed to a 4.0-kb segment located almost entirely within an intron of the E beta gene. The recognition that the points of crossing-over in all five recombinants studied are clustered in a relatively small area of the I region provides further evidence for a hot spot of recombination associated with the E beta gene. PMID- 2896000 TI - Bovine liver cDNA clones encoding a precursor of the alpha-subunit of the mitochondrial ATP synthase complex. AB - cDNA clones encoding a precursor of the alpha-subunit of the mitochondrial ATP synthase complex have been isolated from a bovine liver cDNA library using the alpha-subunit gene from Saccharomyces cerevisiae as a probe. Analyses of the nucleotide sequence of these cDNA clones reveal that the bovine liver ATP synthase alpha-subunit is initially synthesized as a precursor with an aminoterminal extension 43 amino acids in length. This aminoterminal presequence contains seven basic residues, no acidic residues, and seven polar uncharged serine and threonine residues. A single mRNA species, approximately 1.85 kb in length, was detected for the ATP synthase alpha-subunit precursor in both bovine liver and heart. PMID- 2895999 TI - Differential uptake of isomeric 2-bromohydroquinone-glutathione conjugates into kidney slices. AB - 2-Bromo-(diglutathion-Syl)hydroquinone (2-Br-[diGSyl]HQ) is a more potent nephrotoxicant than any of three mono-substituted isomers. The reason for this differential toxicity is unknown. We now report that the rate of uptake of 2-Br (diGSyl)HQ, 2-Br-3-(GSyl)HQ, 2-Br-5-(GSyl)-HQ and 2-Br-6(GSyl)HQ by kidney slices was 2.4, 1.2, 1.0 and 0.3 nmoles/mg/10 min, respectively. AT-125 (0.5 mM) inhibited gamma-glutamyl transpeptidase (GGT) in intact and homogenized kidney slices by 47% and 92%, respectively and decreased the accumulation of the isomeric [35S]-conjugates by 49%, 21%, 25% and 30%, respectively. The data suggest that the accumulation of 2-Br-(GSyl)HQ conjugates into isolated kidney slices may in part be mediated by GGT and that the more extensive renal uptake of the di-substituted conjugate may be partially responsible for its enhanced nephrotoxicity. In addition, 2-Br-(diGSyl)HQ gave rise to the most covalently bound material of the different isomers studied suggesting that both physiological and biochemical factors contribute to the potent and selective nephrotoxicity of this compound. PMID- 2896001 TI - Centrally mediated activation of tyrosine hydroxylation in rat adrenals by thyrotropin-releasing hormone. PMID- 2896002 TI - Behavioral impairments, brain lesions and monoaminergic activity in the rat following recovery from a bout of thiamine deficiency. AB - Learning impairments were measured in rats following recovery from a subacute bout of thiamine deficiency. Behavioral training was carried out in an automated T-maze, beginning with paired run spatial delayed non-matching to sample (PR-1), then light-dark discrimination (LD), light-dark discrimination reversal (LD-R), spatial discrimination (SD), spatial discrimination-reversal (SD-R), and finally retraining on the original paired run task (PR-2). Comparable deficits were observed for PR-1 and PR-2, thus demonstrating long-lasting impairment on delayed non-matching to sample. Experimentals performed as well as controls on LD and LD R. Two experimental animals were unable to perform above chance on the simple SD task. The remaining 15 experimental animals were equivalent to controls on several measures of SD and SD-R performance (errors to criterion, number of animals reaching criterion, correct responses in last 60 trials) although they were significantly worse than controls on both PR-1 and PR-2. Taken together, these results indicate an impairment of representational memory (PR-1, PR-2) with a spared capacity for dispositional memory (LD, LD-R, SD, SD-R) as defined by Thomas and Spafford (Behav. Neurosci., 1984, 98: 394-404). Histological analyses of left hemispheres revealed a high incidence (94%) of thalamic lesions, specifically within the intralaminar nuclei and ventral parts of the mediodorsal nucleus; and an absence of detectable changes in other structures, including the mammillary bodies, hippocampus, cortex, and locus coeruleus. In the right hemispheres, assays of monoamines and metabolites in 17 brain regions showed significant reduction only for norepinephrine in entorhinal cortex. All animals that were selectively impaired on the paired-run task had both the medial thalamic lesions and reduction in entorhinal norepinephrine. PMID- 2896003 TI - Molecular polymorphism of various HLA-D subregions and rheumatoid arthritis. AB - In Caucasian populations, rheumatoid arthritis (RA) is generally associated with serologic HLA-DR4 specificity. In order to refine this correlation in the HLA-D region, we used six different probes pertaining to this locus: DR beta, DQ beta, DQ alpha, DO beta, DP beta and DP alpha. In this step, pooled RA and control DNA were hybridized with DR beta and DQ beta probes after digestion with 12 different endonucleases. Some bands appeared specific in the RA pool. In fact, with genomic DNA from 13 unrelated typed RA patients and 12 matched or partially matched control cells, these bands were revealed to be related to DR4 and/or DR1, with DR beta and DQ beta probes hybridizing BamHI, EcoRV, PvuII and StuI digests. With other probes, no differences could be related to RA disease. The polymorphism detected by these probes was suggestive of a gradient of decreasing complexity from DR beta to DO beta through DQ beta and DP beta, which could reflect discrete functions of each subregion. PMID- 2896004 TI - [Action of several amino acids on the vestibular receptors in the frog]. PMID- 2896005 TI - RFLPs of the Ha-ras1 protooncogene in subjects with colon-rectal carcinomas. PMID- 2896006 TI - Structure and methylation state of the human transferrin receptor gene: preliminary analysis on tumor cell lines, primary tumors and some normal tissues. PMID- 2896007 TI - [A new technic for determining anti-TSH receptor antibodies: the TBIAb assay]. PMID- 2896008 TI - [Strategy for the identification of new DNA polymorphisms: diagnostic application as genetic markers]. PMID- 2896009 TI - DNA polymorphisms as potential genetic risk markers for cardiovascular diseases. PMID- 2896010 TI - [Changes in monoamine neurotransmitter metabolism in brain ischemia measured by in vivo voltammetry]. AB - A preliminary work with in vivo voltammetry (IVV) in the ischemic brain had been performed by the authors in rats after cardiac arrest, which showed that the IVV system is useful to investigate ischemic brain. In the present report, IVV was applied to ischemic brain by 4-vessel occlusion in rat and changes in dopamine and serotonin metabolism were investigated by measuring peak 2 (3,4 dihydroxyphenylacetic acid, DOPAC) and peak 3 (5-hydroxyindoleacetic acid, 5 HIAA) in the striatum. The change of cerebral blood flow (CBF) were also assessed by a temperature-controlled thermoelectrical method in the striatum of the same model. The heights of peaks 2 and 3 were significantly increased to 600-900% and 200-300% respectively in the striatum during 30 minutes of 4-vessel occlusion. The increase of each peak was maximum at 10 minutes after occlusion. These changes may reflect that release of monoamine neurotransmitters is increased by the ischemia and outward transport of their metabolites are disturbed. On the other hand, after reperfusion by release of carotid occlusion, the heights of peaks 2 and 3 rapidly decreased below the control values, thereafter, peaks 2 and 3 gradually increased to over control values at 180-210 minutes after reperfusion. rCBF in the striatum decreased to almost 0 ml/100 g/min during 4 vessel occlusion ischemia and increased to over control values transiently for 30 minutes after reperfusion, followed by gradual decrease for about 240 minutes. Since monoamine neurotransmitters are known to have various effects on cerebral metabolism and CBF, their disorders may contribute to the change of CBF and the development of postischemic brain damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896011 TI - Ultrasonography in undescended testes. AB - The position of an undescended testicle is of importance for choice of therapy. The aim of this study was to investigate whether the anatomic positions occupied by undescended testicles could be detected by an objective method. Real-time ultrasonography was performed in 83 patients with 123 undescended testicles. Patient compliance was 97 per cent. The testis was demonstrated as an echo-poor, oval structure in 113 of 119 examinations (95%). By determining the relation of the testis to definable anatomic landmarks in the inguinal region, all positions occupied by the testis could be characterized by ultrasound and the testicles classified accordingly. The relationship of the testis to the external ring was established in 112 cases (94%). Twenty-seven per cent of retractile and 11 per cent of truly undescended testicles were demonstrated in more than one ascended position. Estimation of testicular volume by sonography was unsuccessful compared with intraoperative measurements. PMID- 2896012 TI - The effect of age and cardiac failure on xamoterol pharmacokinetics. AB - 1. Xamoterol is a cardioselective beta-adrenoceptor partial agonist which may have a role in the management of cardiac failure. Excretion is mainly by the renal route. 2. The kinetics of a single 200 mg oral dose of xamoterol were studied in eight elderly (age 67-82 years) volunteers, eight young (age 21-43 years) volunteers; eight patients with mild to moderate cardiac failure and eight age and sex matched controls. 3. Elderly volunteers had a significantly longer time to reach peak concentration (mean +/- s.e. mean 2.1 +/- 0.2 vs 1.1 +/- 0.1 h) and elimination half-life time (27.0 +/- 2.8 vs 16.4 +/- 3.1 h) compared with young volunteers. The renal clearance of xamoterol was lower in the elderly (115 +/- 12 vs 185 +/- 19 ml min-1) and showed a significant correlation with creatinine clearance (r = 0.85, P less than 0.001). 4. There was no significant difference in any of the pharmacokinetic parameters measured in patients with cardiac failure compared with healthy age and sex matched controls. 5. These results suggest that the maintenance dose of xamoterol could be reduced in elderly patients in relation to impairment of renal function. PMID- 2896013 TI - Exercise haemodynamics and maximal exercise capacity during beta-adrenoceptor blockade in normotensive and hypertensive subjects. AB - 1. The effects of atenolol administration on maximal exercise capacity and exercise haemodynamics have been compared in eight normotensive and eight mildly hypertensive subjects, matched for sex, age, body weight, and maximal oxygen uptake, and familiar with maximal exercise testing. 2. Supine and exercise blood pressure, and exercise total peripheral resistance were significantly higher, and exercise cardiac output was significantly lower in the hypertensive than in the normotensive subjects. 3. Administration of atenolol (1 X 100 mg day-1) for 3 days reduced supine and exercise systolic blood pressure, heart rate, and cardiac output, and increased exercise stroke volume. Supine and exercise diastolic blood pressure and exercise total peripheral resistance were unaffected by atenolol. The effects of atenolol did not differ in the normotensive and the hypertensive subjects. 4. Maximal work load, maximal oxygen uptake, and maximal heart rate were reduced to a similar extent in normotensive and hypertensive subjects during atenolol treatment. 5. It is concluded that there is no difference in the effects of short-term atenolol administration on exercise haemodynamics and maximal exercise capacity in normotensive and mildly hypertensive subjects. PMID- 2896015 TI - Ha-ras restriction fragment length polymorphisms in colorectal cancer. AB - The possibility of an association between restriction fragment length polymorphisms (RFLPs) at the Ha-ras gene locus and susceptibility to develop colorectal cancer has been investigated. Leucocyte DNA from 46 carcinoma patients and 49 controls was analysed by Southern blotting to determine the size distribution of restriction fragments containing the variable tandem repeat 3' to the Ha-ras gene. Four predominant allelic fragments were found in both groups (in AvaII digests having sizes of 1.55, 2.0, 2.65 and 3.15 kilobases [kb]), together with a variety of 'rare' alleles (with individual frequencies less than 5%). The overall prevalence of rare alleles was not significantly different between cancer and control groups. The distribution of the common alleles, however, differed significantly. The combined frequency of the two larger alleles (a3 and a4) was approximately twice as high in the cancer group (34%) as in controls (18%) (P less than 0.025), which was reflected in a highly significant increase in the proportion of individuals carrying an a3 or a4 allele. PMID- 2896014 TI - Continuous intragastric delivery of fenoldopam: relationship between plasma concentration and effects on renal function. AB - 1. The pharmacodynamics of the dopamine DA1 agonist fenoldopam were examined in six healthy male volunteers after constant intragastric infusions of fenoldopam at dosages of 0, 10, 25, 50 and 75 mg h-1 for 6 h. 2. Hourly p-aminohippurate (PAH) clearance was used to assess fenoldopam induced renal plasma flow changes. Marked dose-related increases in renal plasma flow were noted with a maximal increase of 65% over baseline values of 711 ml min-1 being seen at the 75 mg h-1 rate. No changes in sodium excretion and glomerular filtration rate were observed. 3. Mean steady-state fenoldopam plasma concentrations were related to mean PAH clearance based on an Emax model (r = 0.996) with an Emax of 1350 ml min 1 and an EC50 of 6.2 ng ml-1. 4. Mean steady-state plasma concentrations of fenoldopam-7-sulphate and fenoldopam-8-sulphate failed to increase with dose but were linearly correlated to mean PAH changes (r = 0.998, r = 0.981 respectively). 5. These results support the concept of extending fenoldopam's duration of action through the development of an oral sustained delivery system. PMID- 2896016 TI - Nutrient sensitivity of gastric emptying of digesta in the preruminant calf. AB - 1. Studies of gastric function were made in preruminant calves fitted with a single abomasal cannula, re-entrant cannulas in the duodenum close to the pylorus and recording electrodes on the pyloric antrum and proximal duodenum. 2. Simultaneous measurements were made of gastric emptying of a saline (9 g sodium chloride/l) meal, myoelectric activity of antral muscle and plasma concentration of somatostatin in jugular blood whilst infusing the duodenum with different solutions. The duodenal infusates were isotonic sodium bicarbonate (300 mosmol/kg), hyperosmolar solutions of NaCl (1000 mosmol/kg), sodium carbonate (500 mosmol/kg), sucrose (1000 mosmol/kg), 41 g emulsified butterfat/kg or 60 mM hydrochloric acid. 3. Infusing the duodenum with isotonic NaHCO3 stimulated intense myoelectric activity of the antral smooth muscle and rapid emptying of the test meal. In contrast, infusions of 60 mM-HCl reduced antral motility and inhibited gastric emptying of digesta. This inhibitory response to HCl infusion was related to a significant (P less than 0.05) increase of somatostatin in peripheral venous blood. 4. The Na2CO3 infusate, like HCl, inhibited gastric motor activity and digesta emptying, but the concentration of circulating somatostatin was only slightly elevated above pre-infusion levels. 5. Compared with the effects of infusing HCl, infusions of emulsified butterfat or hyperosmolar NaCl and sucrose induced a greater intensity of antral motor activity and faster outflow of gastric effluent, although not to the same extent as with isotonic NaHCO3. However, as with isotonic NaHCO3, these infusates did not evoke the release of somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896017 TI - Polyadenylation of mRNA precursors. PMID- 2896018 TI - Transcriptional activity at the 3' end of the actin gene at 5C on the X chromosome of Drosophila melanogaster. AB - Polyribosomal poly(A)+ RNA from stage-specific embryos of Drosophila melanogaster was analyzed by Northern hybridizations to determine the transcription at the 5C actin gene (act5C) and to establish whether these mRNAs are used in translation. A 3' end probe, which contains 30 nucleotides of the actin coding sequence as well as 3'-end-adjacent sequence, hybridizes in addition to the act5C transcript to a smaller transcript 450 nucleotides long. Hybridizations with the 3' end strand-specific probes show that this transcript has the same orientation as the actin gene. This transcript is temporally coexpressed with the act5C gene over most of the developmental stages examined. S1 nuclease mapping and primer extension experiments place its 5' end about 20 nucleotides upstream from the actin translation termination signal. Furthermore, the transcript appears to translate in an in vitro translation system into a protein of 7.4 kDa, as expected from the size of the open reading frame. The data suggest, but do not prove, that the 3'-end-transcribed but untranslated region of act5C may be involved in actin gene expression. PMID- 2896019 TI - Modulation of sodium-cotransport systems by other ions. AB - After a brief review of Na+-cotransport systems which also accept other ions as co-ions or modifiers, modulation of the Na+-L-glutamate transport system in rabbit renal brush border membranes by K+ and H+ is discussed in more detail. Intravesicular K+ increases the initial uptake rate and electrogenicity of the cotransport. This effect of K+ is attributed to the formation of a K+-carrier complex that moves much more rapidly than do the other complexes. The resulting shift in rate limitancy (relative increase in overall rate over the relative increase in rate of step under consideration) from an electroneutral towards a charge-translocating pathway unmasks the electrogenicity of the initial L glutamate uptake. A positive correlation between relative rate limitancy of the electrogenic pathway and electrogenicity is demonstrated supporting this model. Protons, in addition to acting as co-ions, modify Na+-glutamate cotransport by increasing both the initial rate and the electrogenicity of uptake. This phenomenon is assumed to represent a transition of the transport system from a carrier-like to an open channel-like translocation mode. Thus, the intrinsic properties of Na+-cotransport systems may vary under the influence of other ions. This holds true in particular for the electrogenicity of the initial transport rate which may change independently of alterations in charge stoichiometry. PMID- 2896020 TI - Properties and regulation of the H+-ATP synthase of mitochondria. AB - A brief survey is made of the function of the H+-ATP synthase of mitochondria with emphasis on how it is regulated. A main regulatory factor is a low molecular weight protein whose binding to the enzyme appears to be essential for optimal accumulation of ATP as driven by electron transport. The ATP synthase is also controlled by ADP that, by binding to a site in the enzyme, inhibits ATP hydrolysis. Data on the spontaneous synthesis of a tightly bound ATP are discussed. Apparently, this requires proper subunit interactions to yield a competent catalytic site. PMID- 2896021 TI - The 'Ca-voltage' hypothesis for neurotransmitter release. AB - The 'Ca-voltage' hypothesis for neurotransmitter release was reinvestigated by studying the kinetics of neurotransmitter release. These were independent of changes in intracellular or extracellular Ca2+ concentration. It is concluded that initiation and termination of release do not result from rapid entry and removal of Ca2+ although Ca2+ is essential for release. Quantal release of transmitter requires depolarization-dependent transformation of a membrane molecule from an inactive form T to a Ca2+-binding form S. The depolarization dependent T----S transformation initiates release in the presence of Ca2+. The S- --T transformation upon repolarization stops release even though the Ca2+ concentration at release sites is still high. PMID- 2896022 TI - [Biochemical characteristics of a muscle perfusate and its effects on mediator release in the neuromuscular synapse]. AB - Histidine-containing compounds (HCC) were found, using diazoreaction and reaction with diethylpyrocarbonate, a specific histidine reagent, in the perfusate of the frog hindlimb vasculature. After gel filtration on sephadex G-25 about 80% of HCC were eluted with a fraction with molecular mass less than 5000 kD. The studies of the perfusate influence on the characteristics of quantum secretion of transmitter in the preparation of frog cutaneopectoral muscle have shown that the perfusate increased the quantum content of end-plate potentials (EPP) due to increasing binominal parameter and decreasing frequency of miniature EPP. The characteristics of presynaptic action of the perfusate were similar to those of exogenous histidine. PMID- 2896023 TI - [Effect of M and N-cholinoblockers on the excitability of the dorsal hippocampus in acute alcoholic intoxication]. AB - It has been established in chronic experiments on rabbits that acute alcohol intoxication increased the after-discharge thresholds in response to electrical stimulation of dorsal hippocampus. It has been shown that neurotropic agents selectively blocking M- or N-cholinoceptors exerted various effects. M-cholino blocker methamizol (1 mg/kg, i. p.) decreased the excitability of dorsal hippocampus, potentiated EEG and behavioural effects of alcohol intoxication. N cholinoblocker etherophen (IEM-506, 20 mg/kg, i. p.), on the contrary, increased the excitability of dorsal hippocampus and reduced behavioural effects of alcohol administration. PMID- 2896024 TI - [Modulation of excitation transfer in the intracardiac ganglionic system by the opioid peptide dermorphin]. AB - The aim of the study was to determine whether opioid peptides could modulate the intracardiac ganglionic excitation. It has been shown that postganglionic impulse activity recorded in the frog intracardiac nerve was inhibited by endogenous amphibian opioid peptide-dermorphin (10(-12)-10(-6) M). The inhibition was blocked by naloxone (10(-5) M). Dermorphin (10(-6) M) had no influence on transitory impulse activity in the intracardiac postganglionic sympathetic fibers. It is suggested that opioid peptides take part in the mediatory process in the intracardiac ganglia. PMID- 2896025 TI - [Action of benzodiazepines on the immune response]. AB - The action of benzodiazepine receptor agonists--diazepam and tazepam--on the immune response was studied in CBA mice. It has been shown that benzodiazepine at low doses of 0.5 and 1 mg/kg stimulates and at a dose of 8 mg/kg suppresses the rosette-forming reaction to immunization with 5 X 10(8) sheep red blood cells. Diazepam and tazepam fail to change the immune response if the immunization dose is 5 X 10(6). The dose-dependent effect of diazepine (ranging from stimulation to inhibition) may be caused by different benzodiazepine receptors involved in the process. It is suggested that a certain intensity of the immune response is needed for the manifestation of the immune modulating action of benzodiazepine. PMID- 2896026 TI - [Effect of pertussis antibodies on the induction of suppressor cells of humoral immunity in mice]. AB - Standard pertussis agglutinative serum as well as antibodies to total and purified protective pertussis antigens, isolated from the serum by immunoadsorption technique, were studied. The treatment of donors with pertussis antibodies affected the T-suppressor formation, induced by high doses of sheep red blood cells, as was shown on the model of syngeneic transfer. Immunomodulating effect of antibodies, complementary to immunogen fraction of pertussis cells, was decreased. It was suggested that the observed antilymphocyte activity of antipertussis antibodies could play a certain role in postvaccination complications after corpuscular pertussis vaccine administration. PMID- 2896027 TI - [Regulation of hormonal secretion and DNA synthesis in the lactotrophs of the rat adenohypophysis in vitro in primary cell cultures]. AB - Changes in DNA synthesis in lactotrophs of primary monolayer cultures of the rat pituitary cells were studied, using immunoperoxidase staining in combination with autoradiography. Pituitary cell cultures were treated for 3 days with thyroliberin (TRH), bromocriptine (CB154) or somatostatin (SRIF). The proportion of lactotrophs labelled with 3H-thymidine in the total pool of labelled cells served as a criterion for the estimation of DNA synthesis in prolactin-secreting cells. Prolactin secretion by the same cultures was measured by homologous radioimmunoassay. TRH (10 ng/ml) stimulated DNA synthesis in the total population of pituitary cells, but not in lactotrophs. SRIF decreased selectively the proliferation of lactotrophs, but failed to depress or even stimulated DNA synthesis in some cell types of the rat pituitary gland in the cultures. The quantitative method of studying DNA synthesis in anterior pituitary may be used to evaluate the effects of a number of biologically active compounds on various cell systems. PMID- 2896028 TI - S-100 beta positive T cell leukemia. AB - We reported a peculiar case with T cell leukemia. The patient was a 34-year-old woman showing extensive splenomegaly and marked leukemic cell proliferation and running a rapid fatal clinical course. The leukemic cells were morphologically ordinary lymphocytes showing suppressor/cytotoxic(s/c) T cell phenotypes and containing S-100b protein. Southern blot analysis revealed rearrangement of the beta chain genes of the T cell receptor (TcR) of the leukemic cells. Because these phenotypic and morphologic features were identical with those of S-100 beta+T lymphocytes (S-100 beta +TL) in normal human peripheral blood, we regarded this case as S-100 beta +T cell leukemia. We discussed clinicopathological features of S-100 beta +T cell leukemia/lymphoma by assessing similar cases reported so far. S-100 beta +T cell leukemia/lymphoma is a new type of s/c T lymphocytic leukemia/lymphoma with aggressive features. PMID- 2896029 TI - Multiple polymorphic sites in factor X locus. AB - The structure of factor X (FX) gene was analyzed in five FX deficient pedigrees with four different variants of the disease, as well as in 50 normal subjects. Genomic DNA from the deficient patients and the normal controls was digested with 12 restriction endonucleases and hybridized with a FX cDNA probe. The results seemingly exclude gross gene deletions or rearrangements in the deficient patients. A variety of polymorphic sites (ie, EcoRI, HindIII, PstI, PvuII, TaqI) was observed within the FX locus and their relative frequency was established. Intriguingly, a highly polymorphic region for the PvuII endonuclease was identified and located approximately 3 kilobases (kb) from the last 3' exon. These polymorphisms allowed us to analyze the allelic segregation in a FX deficient family and to identify a homozygous subject. PMID- 2896030 TI - Lymphocyte aggregation in response to adrenergic stimulation. AB - A nonanemic chronic lymphocytic leukemia patient with nearly 500,000 lymphocytes/microL underwent leukapheresis when she presented with CNS symptoms and retinal vascular engorgement. Respiratory distress developed during the cell separator run, which led us to ask whether the procedure could have changed the adhesive properties of her cells. C5a desarginine, N-f-Met-Leu-Phe, adenosine diphosphate, and collagen all failed to aggregate her lymphocytes in vitro, but arachidonic acid, excess free calcium, and 4 mumol/L epinephrine did aggregate the cells. Arachidonate-induced aggregation appeared to be a toxic phenomenon: the ED50 for aggregation was statistically indistinguishable from that for cytotoxicity, and aspirin only mildly blunted the response. In contrast, epinephrine-induced aggregation was not associated with lactic dehydrogenase release or the loss of trypan blue exclusion and was blunted by propranolol; radiopindolol-binding studies confirmed the presence of a beta-adrenergic receptor. There were approximately 3,000 receptors/cell, with no statistically significant difference between normal and chronic lymphocytic leukemia B cells or between B cells and T cells (separated by rosetting techniques). The Kd for the B cells' receptor, however, was less than that for T cells by a factor of ten (P less than .01). We conclude that B cells may aggregate when stimulated and that they--like T cells--have beta-adrenergic receptors. Adrenergically mediated changes in B cell adhesiveness may play a role in regulating lymphocyte traffic; in the rare patient with truly enormous B cell counts, we postulate that they may be an occasional cause of morbidity. PMID- 2896031 TI - Molecular analysis of clonality and bcr rearrangements in Philadelphia chromosome positive acute lymphoblastic leukemia. AB - Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) patients consistently show a rearrangement in a 5.8-kilobase length of chromosome 22, referred to as the breakpoint cluster region (bcr). In Ph1-positive acute lymphoblastic leukemia (ALL), the breakpoint in chromosome 22 is more heterogeneous and, in some instances, does not occur within this region. In such cases the cell of origin of the neoplastic clone and the relationship of the disease to CML has remained obscure. We have analyzed the bcr rearrangement in the malignant cells from three patients who presented with Ph1-positive ALL and who in cytogenetic studies had shown evidence of variable involvement of myeloid cells in the Ph1-positive clone. Rearrangements in bcr typical of most cases of CML were detected in purified granulocyte preparations from two of the ALL patients (nos. 1 and 2) and in the blasts from patient 3 at the time of her terminal relapse. In the same analysis the simultaneously obtained granulocytes from patient 3, however, did not show any evidence of bcr rearrangement. Patient 3 was also heterozygous for the BamHI polymorphism in the X-linked hypoxanthine phosphoribosyltransferase (HPRT) gene, thus permitting a different method of clonal analysis based on methylation differences in active and inactive alleles. When DNA from her granulocytes that had shown no bcr rearrangement was hybridized to an HPRT probe, a pattern typical of a polyclonal population was seen. A similar pattern was exhibited by her marrow fibroblasts. In marked contrast, her simultaneously isolated blasts showed an unambiguous monoclonal pattern. These findings demonstrate the origin of the disease in the first two patients in a cell with myelopoietic as well as lymphopoietic potential and confirm the restricted lymphoid cell origin of the neoplastic clone in the third Ph1-positive ALL patient. Furthermore, they indicate that different target cells for transformation within the hematopoietic system may be affected by very similar bcr rearrangements. PMID- 2896032 TI - Changing controversies in surgery for angina. AB - Coronary artery surgery has evolved rapidly since its introduction 20 years ago. Few operations have been subjected to such scrutiny. As a result many details of prognosis have been clarified, but the development of coronary angioplasty, thrombolysis and the internal mammary artery graft have created new controversies. PMID- 2896033 TI - The effects of neosurugatoxin on evoked catecholamine secretion from bovine adrenal chromaffin cells. AB - 1. The effect of neosurugatoxin (NSTX), a toxin from the Japanese ivory mollusc (Babylonia japonica), on the nicotinic response of bovine adrenal chromaffin cells was examined. 2. NSTX inhibited acetylcholine- and nicotine-induced catecholamine secretion from the cultured cells with an IC50 against 5 microM nicotine of 30 nM. 3. This inhibitory effect was reversible and independent of the presence of agonist. 4. NSTX had no effect on the catecholamine release from cultured cells evoked by 50 mM K+, or 1 microM histamine. 5. NSTX had no effect on the stimulation of phosphatidylinositol metabolism evoked by 100 microM muscarine. 6. These results suggest NSTX may be useful as a nicotinic receptor probe in tissues such as the adrenal and sympathetic ganglia where alpha bungarotoxin is ineffective. PMID- 2896034 TI - Phentolamine lacks alpha 2-adrenoceptor agonist activity in anaesthetized dogs. AB - 1. This study was performed in order to determine whether the blockade of sympathetic vasoconstriction in anaesthetized dogs by phentolamine is due to the antagonist action of the drug at postjunctional adrenoceptors, or is due to depression of neurotransmitter release by an agonist action at prejunctional adrenoceptors. 2. In dogs made areflexic by ganglion blockade with hexamethonium, phentolamine (0.5 mg i.a. or 0.5 mg kg-1 i.v.) elevated or did not affect femoral blood flow. By contrast, clonidine (0.5-2.5 nmol, i.a.) produced femoral vasoconstriction, which was attenuated by prior administration of phentolamine. 3. Prior blockade of prejunctional alpha 2-adrenoceptors with yohimbine (30 micrograms kg-1, i.v.) did not reduce the blocking effect of phentolamine (0.5 mg kg-1, i.v.) on neurogenic vasoconstriction. 4. The results indicate that, in anaesthetized dogs, phentolamine lacks appreciable agonist activity at either prejunctional or postjunctional alpha 2-adrenoceptors. The blockade of neurogenic responses by phentolamine is therefore likely to be due to postjunctional adrenoceptor blockade. PMID- 2896035 TI - Zn2+ stimulates spontaneous transmitter release at mouse neuromuscular junctions. AB - 1. Experiments were carried out to examine the effect of Zn2+ on the rate of spontaneous release of transmitter at the neuromuscular junction of the mouse diaphragm muscle, in the presence and absence of external Ca2+. Miniature endplate potentials (m.e.p.ps) were measured in vitro. 2. Zn2+ markedly elevated the frequency of m.e.p.ps without affecting the resting membrane potential of muscle fibres. This effect was time- and concentration-dependent but was independent of the presence of external Ca2+. In a Ca2+-free bathing solution, Zn2+ frequently produced twitching in several fibers. The twitching dislodged the microelectrode. Replacement of the 10 mM NaCl in the Ca2+-free solution with equimolar KCl overcame this difficulty. The experiments summarized below were done in the Ca2+-free bathing solution which contained 10 mM KCl instead of 10 mM NaCl. 3. The effect of Zn2+ was transient and required a latent period of many minutes. Low temperature (24 degrees C) increased the length of this latent period and reduced the maximum effect of Zn2+. 4. Zn2+ increased the frequency of m.e.p.ps in K+-free (replaced with NaCl) solution. The effect appeared with shorter latency in this solution compared to the standard Krebs-Ringer solution. 5. The effect of Zn2+ was partially antagonized by dantrolene sodium or by neomycin. Both agents also reduced the effect of external Ca2+ on m.e.p.ps in depolarizing solution. 6. Cd2+ and 2,3-bisphosphoglycerate also elevated the frequency of m.e.p.ps in a manner independent of external Ca2+, but the latter compound was much less potent than Cd2+. 7. These experiments provide evidence for a role of intracellularly stored Ca24 in the release of transmitter at the motor nerve terminal. The release of Ca24 from the storage site may be coupled with the metabolism of phosphatidylinositol. PMID- 2896036 TI - Chronic prazosin attenuates the natriuretic response to a modest saline load in anaesthetized rats. AB - 1. The effect of chronic prazosin pretreatment (3 days) on the ability to excrete a modest saline load (i.v. saline, 0.097 ml min-1) was studied in the anaesthetized rat. Three days before the experiment, the drinking water was replaced with 0.5% dextrose (control), 0.015 mg ml-1 prazosin in 0.5% dextrose (low dose) or 0.15 mg ml-1 prazosin in 0.5% dextrose (high dose). 2. The selectivity of the prazosin for alpha 1-adrenoceptors was evaluated in pithed rats. The pressor response to phenylephrine was partially attenuated by the low dose of prazosin and completely attenuated by the high dose of prazosin. The pressor response to clonidine was slightly decreased by the 3 day prazosin pretreatment indicating a selectivity for alpha 1-adrenoceptors. 3. In rats pretreated with the low dose of prazosin, there was a significant decrease in sodium and water, but not potassium excretion as compared to the control group. Captopril failed to alter these effects of the low dose of prazosin. Blood pressure and creatinine clearance were the same in both groups. In rats pretreated with the high dose of prazosin, there was a further decrease in sodium and water but not potassium excretion. However, this dose of prazosin also significantly decreased blood pressure and increased creatinine clearance. A decrease in renal perfusion pressure with an aortic clamp to the same level as that observed with the high prazosin dose also decreased sodium and water but not potassium excretion. The decrease in sodium and water excretion was not as great as that observed with the high dose of prazosin. 4. The results indicate that chronic a,-adrenoceptor blockade with prazosin attenuates the ability to excrete a saline load in a dose-related manner. Whether this inability to excrete a saline load is analogous to the sodium and water retention observed with the clinical use of prazosin remains to be determined. PMID- 2896037 TI - Commentary on Dinan's hypothesis. PMID- 2896038 TI - The dopamine hypothesis survives, but there must be a way ahead. PMID- 2896039 TI - Myocardial infarction: the first 24 hours. PMID- 2896040 TI - Biochemical and histological modifications of the rat retina induced by the cholinergic neurotoxin AF64A. AB - Intraocular injections of ethylcholine mustard aziridinium ion (AF64A) in the rat depressed retinal choline acetyltransferase (ChAT) activity in a dose-dependent manner without any significant change in the content of amino acid neurotransmitters GABA, glycine, aspartate and glutamate. ChAT reduction was already detected 24 h after the injection and persisted for at least one month. In vitro AF64A also inhibited retinal ChAT activity. No changes in muscarinic receptor sites were detected. The histological study showed light cells, characterized by cytoplasmic swelling in the innermost part of the inner nuclear layer and in the ganglion cell layer. We suggest that these light cells are the cholinergic retinal neurons affected by the toxin. In addition, dark cells in the inner nuclear layer, large empty spaces in the outer nuclear layer, inflammatory infiltrate and vascular alterations were also observed in treated retinas. Choline uptake systems in photoreceptors and in endothelial cells or cholinergic perivascular nerve endings may explain the lesions observed in the outer nuclear layer and the vascular alterations. PMID- 2896041 TI - Light and electron microscopic study of tyrosine hydroxylase-immunoreactive neurons within the developing rat arcuate nucleus. AB - The topography, fine structure, and patterns of connections of tyrosine hydroxylase (TH)-immunoreactive tubero-infundibular dopaminergic (TIDA) neurons were examined by light and electron microscopic immunocytochemistry in the arcuate nucleus of 2-, 15- and 30-day-old female Wistar rats. In 2-day-old animals, TH-immunoreactive perikarya were mainly located in the ventrolateral portion of the arcuate nucleus. In 15-day-old rats numerous TH-positive cell bodies were still present ventrolaterally, but a cluster of labeled cells was also apparent in the mediodorsal segment of the nucleus. In the 30-day-old rats, most TH-immunoreactive neurons were concentrated mediodorsally, as seen in the adult. At the ultrastructural level, TH-immunoreactive somata exhibited, in all age groups, a large nucleus surrounded by a thin rim of cytoplasm containing mitochondria, Golgi apparatus, endoplasmic reticulum, multivesicular bodies and lysosomes. These labeled somata were synaptically contacted by unlabeled axon terminals and often laid adjacent to either labeled or unlabeled dendrites. Similarly, in all age groups, labeled dendrites were synaptically contacted by unlabeled axon terminals and were often directly apposed to either labeled or unlabeled perikarya and dendrites, or to tanycytic processes. These results indicate that TIDA neurons establish extensive connections early in development, and that their pattern of intercellular relationships remains qualitatively unchanged from 2 days to adulthood. It is suggested that TIDA neurons may be already functional at birth, and could therefore, influence the maturation of other arcuate neuronal populations. PMID- 2896042 TI - Somatostatin inhibition of anterior pituitary adenylate cyclase activity: different sensitivity between male and female rats. AB - Somatostatin (SRIF) is a potent inhibitor of growth hormone (GH) secretion. Although cyclic AMP (cAMP) has been suggested as intracellular mediator of SRIF action, a complete characterization of its effect and the different sensitivity between male and female animals, has not yet been carried out. In this study SRIF inhibited basal and GH-releasing factor (GRF) stimulated anterior pituitary adenylate cyclase activity with a greater effectiveness in male than in female glands. Similarly SRIF reduction of forskolin-stimulated anterior pituitary adenylate cyclase activity, was more pronounced in male than in female animals. By using pertussis toxin (PTX), which uncouples inhibitory receptors from adenylate cyclase catalytic subunit, SRIF inhibition of both basal and forskolin stimulated adenylate cyclase activity was nearly abolished. These results show that anterior pituitary SRIF receptors are coupled in an inhibitory fashion with adenylate cyclase enzyme, and that male rat adenohypophyses are more responsive to SRIF inhibition. PMID- 2896043 TI - Brainstem and spinal pathways mediating descending inhibition from the medullary lateral reticular nucleus in the rat. AB - The lateral reticular nucleus (LRN) in the caudal ventrolateral medulla has been implicated in descending monoaminergic modulation of spinal nociceptive transmission. Experiments were undertaken to examine the organization of pontine and spinal pathways mediating inhibition of the tail-flick (TF) reflex from the LRN in rats lightly anesthetized with pentobarbital. Microinjections of the local anesthetic lidocaine ipsilaterally or bilaterally into the dorsolateral pons blocked stimulation-produced inhibition of the TF reflex from the nucleus locus coeruleus/subcoeruleus (LC/SC), but had no effect on descending inhibition produced by microinjection of glutamate into the LRN. Thus, adrenergic modulation of the TF reflex from the LRN is not mediated by activation of spinopetal noradrenergic neurons in the LC/SC. The funicular course of descending inhibition produced by focal electrical stimulation in the LRN was studied in separate groups of rats by reversibly (local anesthetic blocks) or irreversibly (surgical transection) compromising conduction in the dorsolateral funiculi (DLFs) at the level of the cervical spinal cord. Bilateral lidocaine blocks in the DLFs significantly shortened control TF latencies and more than doubled the intensity of electrical stimulation in the LRN necessary to inhibit the TF reflex (153 +/- 29% increase from control); changes in these parameters produced by unilateral blocks of the DLFs were not statistically significant. Ipsilateral or bilateral transections of the DLFs significantly increased the intensity of electrical stimulation in the LRN to inhibit the TF reflex (110 +/- 24% and 265 +/- 46% from control, respectively). Neither lidocaine blocks nor transections of the DLFs completely blocked the descending inhibitory effects of electrical stimulation in the LRN. The DLFs appear to carry fibers mediating LRN stimulation-produced inhibition of the TF reflex as well as tonic descending inhibition of spinal reflexes. The results of the present study indicate that (1) adrenergic modulation of the nociceptive TF reflex from the LRN does not depend on a rostral loop through the pontine LC/SC, and (2) descending inhibitory influences from the LRN are contained in, but not confined to, the dorsal quadrants of the spinal cord. PMID- 2896044 TI - Fictive locomotion in the lamprey; a comparison using bicarbonate and HEPES buffers. AB - Fictive locomotion in the lamprey, elicited by N-methyl-DL-aspartate or D glutamate, was compared in two buffer solutions, one using bicarbonate, the other using HEPES. No differences were observed in burst proportion, cycle length, or phase lag per segment between these buffers solutions. These data indicate that HEPES-buffered artificial cerebrospinal fluid, which does not require gassing with carbon dioxide to maintain pH, may be a suitable alternative to bicarbonate buffered artificial cerebrospinal fluid. PMID- 2896045 TI - Cholinergic excitation and inhibition in the visual thalamus of the cat- influences of cortical inactivation and barbiturate anesthesia. AB - Neuronal responses to microiontophoretically applied pulses of acetylcholine (ACh) were recorded in the perigeniculate nucleus (PGN) and dorsal lateral geniculate nucleus (dLGN) of the cat. In the PGN, ACh inhibited 95% of the cells under N2O/O2-halothane anesthesia. Systemic application of sodium pentobarbitone did not abolish ACh inhibition. In the dLGN with N2O-halothane, ACh increased firing rates of neurons before (88%) and after (78%) interruption of their direct retinal inputs by photocoagulation of the receptive field area on the retina. Functional inactivation of the corticogeniculate loop by cooling of the ipsilateral visual cortex did not selectively influence ACh sensitivity in the retinally deafferented dLGN. It is concluded that ACh exerts a direct, excitatory action on geniculate neurons. Infusion of sodium pentobarbitone resulted in reduction of ACh firing rates to about 30% of the control values in 35% of the normally innervated cells (65% of that sample not being excited by ACh), whereas excitatory ACh responses after retinal deafferentation were completely blocked by the barbiturate. It is concluded that pentobarbitone influences direct ACh excitation, but not cholinergic disinhibition in the dLGN or ACh inhibition in the PGN. Possible differential effects of pentobarbitone on nicotinic and muscarinic types of ACh responses are discussed. PMID- 2896046 TI - Establishment and properties of separate cultures of enteric neurons and enteric glia. AB - In this paper methods are described for the preparation of two types of culture derived from myenteric explants: (a) highly enriched neuronal cell cultures, and (b) purified glial cells (greater than 98%). Both procedures combine the technique of antibody complement-mediated cytolysis with the use of an antimitotic agent. Immunohistochemical methods were used to compare the purified cells to their counterparts in mixed cultures (see accompanying paper). Antibodies to the glycoprotein Thy-1 and the monoclonal antibody A2B5 which recognizes gangliosides, labelled the cell surface of all enteric neurons in enriched cultures while subpopulations of the neurons expressed the Leu 7 carbohydrate epitope, the neurotransmitter 5-hydroxytryptamine and the neuropeptides substance P, methionine-enkephalin and vasoactive intestinal polypeptide. Autoradiographic experiments show that a subpopulation of enriched neurons exhibit high-affinity uptake sites for gamma-[3H]aminobutyric acid (GABA). All purified enteric glia continue to express the calcium binding protein S100, the basement membrane glycoprotein laminin and the antigens recognized by the A2B5 antibody, and subpopulations of glia are labelled by the monoclonal antibodies LB1 which binds to GD3 gangliosides, and Leu 7. Thus enteric neurons and glia can survive independently of each other and express molecular properties which are present in cultures normally containing both cell types. PMID- 2896047 TI - Opioid peptides in pituitary gland, brain regions and peripheral tissues of spontaneously hypertensive and Wistar-Kyoto normotensive rats. AB - The concentrations of beta-endorphin (beta-END), dynorphin (DYN) and methionine enkephalin (MEK) in pituitary, brain regions, heart, kidney and adrenal of 8 week old male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats were determined by radioimmunoassay and compared. The brain regions examined were hypothalamus, striatum, pons + medulla, midbrain and cortex. The concentration of beta-END in pituitary of SHR rats was 49% higher than those of WKY rats. The concentration of beta-END in the striatum of SHR rats was 71% lower as compared to WKY rats. The concentration of beta-END in the heart, adrenals and kidney of SHR rats was significantly lower (92, 48 and 57%, respectively), than those of WKY rat tissues. The concentration of DYN in pituitary, striatum and heart were lower by 38, 55 and 46%, respectively, in SHR compared to WKY rats, but in hypothalamus it was greater (33%) than in WKY rats. The concentration of DYN in other brain areas and in kidney and adrenal did not differ. The tissues of SHR and WKY rats which showed significant difference in the concentration of MEK were pituitary, pons + medulla, cerebral cortex and adrenals. The concentration of MEK was greater in SHR rats with pons + medulla, cortex and adrenals showing 33, 40, 268% higher levels, respectively, over the WKY rat tissues. However, the concentration of MEK in pituitary of SHR rats was 40% lower than that of WKY rats. These studies suggest that the endogenous opioid peptides of both central and peripheral tissues may be important in the regulation of blood pressure in SHR rats. PMID- 2896048 TI - Endogenous ligands for the quisqualate receptor: presence in rat brain cortex synaptic vesicles. AB - The presence in highly purified rat brain cortex synaptic vesicles of endogenous ligands for rat brain quisqualate receptors was investigated. The vesicles were extracted, and their contents fractionated by high voltage electrophoresis. Endogenous ligands were detected by a radioreceptor assay in which such ligands competed with 50 nM L-[3H]glutamate for binding to quisqualate receptors present in rat brain postsynaptic densities (PSDs). Binding of L-[3H]glutamate to N methyl-D-aspartate (NMDA) receptors, also present in PSDs, was blocked by 100 microM NMDA. We found that the endogenous ligands present in brain cortex synaptic vesicles for quisqualate receptors, were glutamate and aspartate, in a molar ratio of about two to one. The quisqualate receptor had an affinity 130 fold higher for glutamate (Kd 0.3 microM) than for aspartate, and the latter amino acid also showed a marked negative cooperative for binding (Hill number 0.29, against 0.67 for glutamate). These findings suggest that glutamate is the natural transmitter that activates quisqualate receptors at some central excitatory synapses, and also that aspartate may be a classical transmitter, the receptor for which still remains to be shown. PMID- 2896049 TI - Role of N-methyl-D-aspartate receptors in the induction of synaptic potentiation by burst stimulation patterned after the hippocampal theta-rhythm. AB - Short bursts of high frequency stimulation produce maximal long-term potentiation (LTP) at Schaffer-commissural synapses on CA1 neurons in hippocampal slices when the bursts are spaced 200 ms apart. A burst to one input (S1) does not induce LTP but 'primes' the postsynaptic neurons such that 200 ms later the postsynaptic response to a burst to a second input (S2) is greatly enhanced and LTP is induced. The role of N-methyl-D-aspartate (NMDA) receptors in this response enhancement and LTP induction was studied by perfusing slices with the NMDA antagonist, 2-amino-5-phosphonovalerate (AP5). AP5 (100 microM) had no effect on the field excitatory postsynaptic potential evoked by single pulse stimulation, but completely eliminated both the decremental short-term potentiation (lasting less than 10 min) and stable LTP effects elicited by burst stimulation. AP5 reduced the response to a non-primed burst by about 10% and reduced the relative enhancement of a primed burst response by about 35%. These results indicate that part of the postsynaptic response to a primed burst is mediated by NMDA receptors and that this component is necessary for all forms of synaptic potentiation (including LTP) resulting from burst stimulation. The similarity of the short bursts with the complex-spike discharges of hippocampal neurons as well as the 200 ms optimal interval with the period of the hippocampal theta-rhythm suggest links between theta and the NMDA receptor in the induction of hippocampal synaptic plasticity. PMID- 2896050 TI - Angiotensin II receptors in the lumbar spinal cord of the rat. AB - Locations of cells responsive to microiontophoretically applied angiotensin II (AII) were compared to distributions of AII receptor binding sites identified by autoradiography in the lumbar enlargement region of the rat spinal cord. Angiotensin II receptor binding sites were densely concentrated in the superficial layers of the dorsal horn. Considerably lower densities of binding sites were present in the remaining gray matter. Effects of microiontophoretically applied AII on lumbar spinal cord cells did not vary with location within the gray matter. AII facilitated firing of most cells in the lumbar cord whether the cells were in superficial or deeper laminae of the dorsal horn or in the ventral horn. The distribution of AII binding sites and the distribution of cells that were responsive to AII suggest that AII may play a role in modulating both sensory and motor functions of the spinal cord. PMID- 2896051 TI - Microdialysis measurement of oxytocin, aspartate, gamma-aminobutyric acid and glutamate release from the olfactory bulb of the sheep during vaginocervical stimulation. AB - Concentrations of oxytocin and amino acids were measured in microdialysis samples taken from the olfactory bulbs of 5 conscious, oestrogen-treated ewes before, during and after a 10-min period of vaginocervical stimulation. Results showed that vaginocervical stimulation induced significant increases in concentrations of oxytocin, aspartate, gamma-aminobutyric acid (GABA) and glutamate in dialysis samples. Concentrations of other amino acids measured were not affected. These findings show that vaginocervical stimulation produces significant changes in neurochemical release in the olfactory bulbs of sheep. Such changes may be involved in the induction of maternal behaviour of the olfactory recognition of offspring. PMID- 2896052 TI - Demonstration of serotoninergic axon terminals on somatostatin-immunoreactive neurons of the anterior periventricular nucleus of the rat hypothalamus. AB - Using a combination of electron microscopic autoradiography and immunocytochemistry, the connections between serotoninergic axons and somatostatin neurons of the anterior periventricular nucleus of the rat hypothalamus were examined. The serotoninergic elements were identified after selective uptake of tritiated serotonin and the somatostatin neurons with immunocytochemistry. Synaptic connections between labeled serotoninergic nerve endings and somatostatin-immunoreactive neurons were observed. This finding provides morphological evidence for a direct influence of serotoninergic elements on somatostatin neurons of the anterior periventricular nucleus projecting to the median eminence of the hypothalamus. PMID- 2896054 TI - Excitatory amino acid-evoked membrane currents and excitatory synaptic transmission in lamprey reticulospinal neurons. AB - The characteristics of excitatory amino acid-evoked currents and of excitatory synaptic events have been examined in lamprey Muller neurons using voltage clamp and current clamp recording techniques. Application of glutamate evoked depolarizations associated with a decrease in input resistance. The reversal potential of the responses was -35 mV. Under voltage clamp conditions, a series of excitatory amino acid agonists evoked inward currents associated with little or no increase in baseline current noise. The order of potency of the excitatory amino acid agonists was quisqualate greater than kainate greater than glutamate greater than aspartate, while N-methyl-D-aspartic acid (NMDA) was inactive. Inward currents evoked by glutamate, as well as by kainate and quisqualate were attenuated reversibly by 1 mM kynurenic acid (KYN). In contrast, glutamate-evoked currents were not affected by 100 microM D(-)-2-amino-5-phosphonovaleric acid (APV), a selective NMDA antagonist. Spontaneously occurring and stimulus-evoked excitatory postsynaptic events were antagonized reversibly by 1 mM KYN. At this concentration, KYN had no effect on membrane potential, input resistance, or excitability of the cells. In contrast, excitatory postsynaptic currents were unaffected by APV. It is concluded that both glutamate responses and excitatory synaptic transmission in lamprey Muller neurons are mediated by non-NMDA-type receptors and that these receptors are associated with ionic channels with a low elementary conductance. The combined pharmacological and biophysical characteristics of these responses are therefore different from those previously reported in other preparations. Spontaneous (but not stimulus-evoked) inhibitory synaptic events in Muller neurons were blocked reversibly by 1 mM KYN but not by 100 microM APV, suggesting that excitation of interneurons inhibitory to Muller cells was also mediated by non-NMDA receptors. PMID- 2896053 TI - L-glutamate evoked release of GABA from cultured avian retina cells does not require glutamate receptor activation. AB - gamma-Aminobutyric acid (GABA) and L-glutamate are the major inhibitory and excitatory transmitters in the central nervous system. Recent evidence has indicated that L-glutamate may stimulate GABA release by a novel exchange mechanism (Nascimento and De Mello, J. Neurochem., 1985, 45: 1820-1827). Here we provide strong support for this hypothesis by showing that the L-glutamate-evoked release of [3H]GABA from cultured avian retina cells is not dependent on the activation of excitatory amino acid receptors. Retina cells were found to incorporate [3H]GABA into a pool that was released when cultures were treated with L-glutamate (100 microM). This release was unaffected when calcium ions were removed, but was prevented when NaCl was replaced by LiCl. D-Aspartate, which in tracer experiments was shown to be taken into cells by the same carrier as L glutamate, was also able to evoke release of [3H]GABA, with the same requirement for NaCl. In addition, L-glutamate and D-aspartate uptake by retina cells was inhibited in more then 80% when the uptake was measured in the presence of LiCl. As opposed to GABA, the release of acetylcholine (ACh) promoted by L-glutamate showed characteristics of classical mechanisms of neurotransmitter release. Glutamate-induced efflux of ACh was Ca2+-dependent and was not affected when NaCl was replaced by LiCl. Also, D-aspartate was ineffective in eliciting the release of ACh. Even at high concentrations, antagonists of excitatory amino acid receptors were unable to diminish the glutamate-evoked release of [3H]GABA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896055 TI - Muscarinic cholinergic modulation of hypothalamic estrogen binding sites. AB - Studies from other laboratories have demonstrated that agents which interact with the dopaminergic and noradrenergic neurotransmitter systems alter the concentrations of cytosolic hypothalamic estrogen receptors. These results have led to the hypothesis that catecholamine systems are involved intimately with the regulation of brain estrogen receptors. The present study was undertaken to determine if agents from a different neurotransmitter system similarly affect [3H]estradiol binding. The data presented here show that the muscarinic cholinergic agonist, bethanechol, increases the number of cytosolic hypothalamic estradiol binding sites in ovariectomized female rats by as much as 38% above control values. Pretreatment with atropine sulfate, a highly specific muscarinic antagonist, blocked the bethanechol effect. Interestingly, bethanechol failed to alter the concentration of estradiol binding sites in castrated male rats. The results of the present experiments show not only that pharmacological modulation of cytosolic hypothalamic estradiol binding sites is not limited to drugs which interact with catecholaminergic systems, but that such effects may be sex specific. PMID- 2896056 TI - A novel interaction between dynorphin(1-13) and an N-methyl-D-aspartate site. AB - Dynorphin injected intrathecally in the rat results in a neurotoxicity behaviorally expressed as an irreversible loss of the thermally evoked tail-flick reflex. The excitatory amino acid antagonists DL-2-amino-5-phosphonovalerate (APV) and gamma-D-glutamylglycine (DGG) blocked the loss of the tail-flick reflex. The order of potency (APV greater than DGG) suggests that the N-methyl-D aspartate (NMDA) subclass of excitatory amino acid receptors participate in the neurotoxicity. Additionally, intrathecal injection of APV results in a reversible loss of the tail-flick reflex, whereas with DGG doses which block the tail-flick reflex also result in hindlimb paralysis. These data suggest that neurotransmission in the tail-flick reflex pathway is, in part, mediated by NMDA receptors. From these and previous findings it was concluded that dynorphin neurotoxicity results from enhanced, excitotoxic, transmission across these synapses utilizing NMDA receptors. PMID- 2896057 TI - Immunocytochemical identification of long ascending, peptidergic lumbar spinal neurons terminating in either the medial or lateral thalamus in the rat. AB - The peptidergic content of rat spinothalamic tract neurons was investigated by combining the retrograde transport of the fluorescent dye Fluoro-gold with immunocytochemistry for enkephalin, dynorphin or vasoactive intestinal polypeptide. Evidence is presented for the existence of enkephalin and dynorphin in a subpopulation of spinothalamic neurons terminating in the medial thalamus and vasoactive intestinal polypeptide in a subpopulation terminating primarily in the lateral thalamus. PMID- 2896058 TI - Physiological regulation of neurohypophyseal kappa-opiate receptors. AB - Quantitative autoradiography was used to examine the characteristics of kappa opiate receptor binding in neural lobe sections from dehydrated rats and water sated homozygous Brattleboro rats. The density of kappa-sites was decreased by 40% and 44%, respectively, after 5 days of water deprivation or hypertonic saline. Both the density and affinity of kappa-receptor sites were lower in homozygous Brattleboro rats. We suggest that kappa-receptor down-regulation occurs as a result of elevated release of opioid peptides induced by chronic osmotic stimulation. PMID- 2896060 TI - Cation permeability change caused by L-glutamate in cultured rat hippocampal neurons. AB - The ionic mechanism of the membrane permeability changes caused by L-glutamate in hippocampal neurons prepared from 17- to 19-day-old fetal rat in dispersed cell cultures was studied with the whole-cell variation of the patch electrode voltage clamp technique. The cultured hippocampal neurons became sensitive to glutamate 7 days after plating, and thereafter the sensitivity gradually increased. The conductance increase caused by glutamate was voltage-sensitive, decreasing with membrane hyperpolarization at potentials more negative than -40 mV. The relative permeability of glutamate-activated channels to alkali metal and alkaline earth cations was estimated by reversal potential measurements. The alkali metal cations, Li+, Na+, K+, Rb+ and Cs+ were permeant to the glutamate channels, and the selectivity among them was weak. The alkaline earth cations, Ca2+, Sr2+ and Ba2+ were more permeant than the alkali metals. The permeability ratios of these divalent cations relative to Na+ were 2.4 (Ca2+), 2.4 (Sr2+) and 2.8 (Ba2+), respectively. Mg2+ was much less permeant and the permeability ratio (PMg/PNa) was only 0.1. Anion conductance made no contribution to the glutamate-induced current. Functional implications of the glutamate-induced increased in Ca2+ influx were discussed. PMID- 2896059 TI - D1 dopamine receptors in human putamen, frontal cortex and calf retina: differences in guanine nucleotide regulation of agonist binding and adenylate cyclase stimulation. AB - High-affinity binding sites for the D1 dopamine receptor antagonist [3H]SCH 23390 were identified in membranes from human putamen, frontal cortex and calf retina. In frontal cortex binding not only occurred to D1 but also to 5-HT2 receptors. In retina and putamen no binding to 5-HT2 receptors was detected. All further binding experiments in frontal cortex were carried out in the presence of 20 nM mianserin to prevent binding to 5-HT2 receptors. In the 3 tissues, antagonist competition curves were monophasic, whereas competition curves with the agonist dopamine revealed the presence of two binding sites, one having high affinity (RH) (32% in retina, 28% in putamen, and 15% in frontal cortex) and the other having low affinity (RL). In retina, the addition of 100 microM GTP caused a full conversion of RH into RL. In contrast, in frontal cortex, RH sites were not altered by 400 microM GTP or 100 microM 5'-guanylyl-imidodi-phosphate (Gpp(NH)p). In putamen, both guanine nucleotides provoked only a partial conversion of RH into RL. Dopamine (100 microM) produced a 220% and 56% increase in cAMP production in respectively retina and putamen homogenates, while no increase was observed in frontal cortex homogenate. These data may suggest that not all D1 receptors are coupled to the adenylate cyclase system. PMID- 2896061 TI - Altered angiotensin II sensitivity of neurons in the organum vasculosum lamina terminalis region of the spontaneously hypertensive rat. AB - Using in vitro hypothalamic brain slices, differences in angiotensin II (AII) sensitivity of neurons in the organum vasculosum lamina terminalis (OVLT) region were compared between spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY). AII, the AII competitive antagonist saralasin, and L-glutamate were micropressure-applied onto OVLT neurons. AII excitation of SHR neurons was blocked or antagonized by simultaneous application of saralasin, evoked at significantly lower thresholds and displayed exaggerated periods of postactivity compared to OVLT neurons in preparations taken from WKY controls. Neuronal responses to L-glutamate were similar between the two rat strains. Differences in neuronal sensitivity to AII may be causally linked to hypertension in SHR. PMID- 2896062 TI - Dopamine-independent motor behavior following microinjection of rimorphin in the substantia nigra. AB - The motor-activating effects of rimorphin, an opioid peptide derived from prodynorphin, were examined in the substantia nigra pars reticulata of rats. Unilateral microinjections of rimorphin produced dose-dependent contralateral rotational behavior that was antagonized by naloxone, suggesting that these effects were mediated by opiate receptors. Lesions of midbrain dopamine cells with 6-hydroxydopamine (6-OHDA) produced a 95% or greater depletion of tyrosine hydroxylase in the striatum ipsilateral to the lesion, but failed to reduce the number of circles made by the rats. In addition to an overall preservation of rimorphin-induced circling in animals with 6-OHDA lesions, 50% of these rats exhibited circling that was at least 2 standard deviations above the mean of animals without lesions. The motor activating effects of rimorphin, thus, appear to occur independently of the nigrostriatal dopamine system; these effects may instead be mediated by GABAergic efferents in the pars reticulata. PMID- 2896063 TI - Calcium-dependent glutamate cytotoxicity in a neuronal cell line. AB - Membranes from the neuroblastoma x embryonic retina cell hybrid cell line, N18-RE 105, bind L-[3H]glutamate with a pharmacologic profile consistent with a 'quisqualate-type' brain L-glutamate receptor. We describe here the cytotoxic effect of L-glutamate receptor agonists on intact N18-RE-105 cells. Cytotoxicity was quantitated by measurement of the release of the cytosolic enzyme, lactate dehydrogenase, into the culture medium after addition of L-glutamate and its analogs to the cell culture medium. L-Glutamate (10 mM) and its confirmationally restricted analogs, quisqualate (1 mM) and ibotenate (10 mM), caused cell lysis. In contrast, similar analogs which do not bind to N18-RE-105 cell membranes (kainic acid, N-methyl-D,L-aspartic acid and gamma-aminobutyric acid) were not cytotoxic. L-Glutamate-induced cytotoxicity was eliminated when calcium-free medium was used. Addition of inorganic or organic calcium channel antagonists also reduced the cytotoxicity of L-glutamate, even when 1.8 mM calcium was present in the medium. Cadmium chloride (10 microM) completely blocked L glutamate toxicity, whereas manganese chloride (150 microM) and lanthanum chloride (25 microM) reduced toxicity by greater than 50%. Dihydropyridine voltage-sensitive calcium channel agonists or antagonists, had little or no significant effect on L-glutamate-induced toxicity. In contrast, the verapamil derivatives, D600 and D888, and the diltiazem derivative, MDL 12,330A reduced L glutamate toxicity by greater than 50%. These results suggest that a subtype of voltage-sensitive calcium channels is involved in the mechanism of L-glutamate receptor mediated cytotoxicity in this cell line. PMID- 2896064 TI - A potassium conductance contributes to the action of somatostatin-14 to suppress ACTH secretion. AB - Somatostatin activates an inwardly rectifying potassium conductance in AtT-20 clonal corticotrophs, a cell line derived from the mouse pituitary gland. The action of somatostatin is blocked by pertussis toxin indicating that a GTP binding protein couples the somatostatin receptor to the potassium channel. The potassium conductance is depressed by cesium. Cesium also attenuates the suppression of adrenocorticotropin hormone secretion by somatostatin suggesting that the increase in potassium conductance plays a role in this action of somatostatin. PMID- 2896065 TI - Development of angiotensin II-sensitive OVLT neurons in SHR and WKY rats. AB - Angiotensin II (AII) sensitivity of neurons in the region of the organum vasculosum laminae terminalis (OVLT) was examined electrophysiologically using in vitro hypothalamic brain slices taken from 4-, 9- and 14-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Micropressure application of AII, its competitive antagonist saralasin, and L-glutamate revealed that neurons in this region of SHR were significantly more sensitive to AII than cells in age-matched WKY preparations. Neuronal sensitivity to L glutamate was similar between SHR and WKY rats at all ages. Following electrophysiological study, hypothalamic and cortical brain slices were assayed for 125I-labelled AII binding. AII receptor binding in the hypothalamic slices from SHR was elevated significantly above binding in WKY hypothalamic slices at 4, 9, and 14 weeks of age. In contrast, AII binding in cortical slices taken from SHR and WKY rats was similar. These data suggest that altered neuronal AII sensitivity is not a consequence of hypertension development in SHR and may contribute to its development. PMID- 2896066 TI - [Clinical trial of isofloxythepin]. PMID- 2896067 TI - [In vitro secretion of somatostatin (SRIH) by human adenomatous somatotropic cells. Relation with somatotropic hormone (GH) release and modulation by thyroliberin (TRH)]. AB - SRIH and GH secretions by GH-secreting adenomatous human pituitary cells were analyzed in vitro in a perifusion system. Of the 13 adenomas studied, 7 secreted SRIH, in variable amounts (50 to 700 pg/ml/2 min., corresponding to 600 10,700 pg for the total experiment. SRIH secretion increased during the perifusion, the highest levels being observed at the end of the perifusion. GH secretion also varied from one adenoma to the other (6 to 500 ng/ml). In most cases, the secretion profiles were negatively correlated, GH secretion decreasing while SRIH secretion was increasing. In the presence of 10(-7) M TRH, GH secretion increased while that of SRIH decreased. The hypothesis of a paracrine and/or an autocrine role for SRIH as well as its possible in situ synthesis are discussed. PMID- 2896069 TI - Pharmacological and biological evidence for differing mechanisms of doxorubicin resistance in two human tumor cell lines. AB - The cellular pharmacology of doxorubicin resistance (DOXR) has most commonly been associated with decreased drug uptake, enhanced drug efflux, cross-resistance to multiple anticancer agents, and the overproduction of a Mr 170,000 cell surface glycoprotein (termed P-glycoprotein). In this study, the pharmacological and genetic characteristics of two newly derived human DOXR sublines were examined. These DOXR sublines were established following continuously increasing DOX exposure until a 222-fold resistant fibrosarcoma subline (HT1080/DR4) and a 285 fold resistant colon adenocarcinoma subline (LoVo/DR5) were developed. However, three major lines of evidence suggest that despite the similar selection strategy, the mechanism of DOXR differs significantly between these two cell lines. First, Western blotting using the C219 antibody specific to P-glycoprotein revealed the overexpression of the Mr 170,000 cell surface glycoprotein in LoVo DOXR cells but not in HT1080 DOXR cells. Second, LoVo DOXR cells are cross resistant to vincristine, actinomycin D, colchicine, etoposide, and gramicidin D, but not to 1-beta-D-arabinofuranosylcytosine. In contrast, HT1080 DOXR cells display cross-resistance to vincristine, actinomycin D, vinblastine, and etoposide; however, they are not cross-resistant to gramicidin D, and show an increased (approximately 18-fold) cross-resistance to 1-beta-D arabinofuranosylcytosine. Third, intracellular DOX accumulation (as measured by [14C]DOX at 1-h and high-performance liquid chromatography analysis) was decreased approximately 2.7-fold in LoVo DOXR cells and approximately 2.0-fold in HT1080/DR4 cells. However, while net accumulation studies in the presence of 5 micrograms/ml verapamil reversed DOXR to parental values in LoVo colon adenocarcinoma cells, it only minimally decreased DOX resistance (12.6%) in HT1080/DR4 cells. Efflux patterns of [14C]DOX were similar for the DOXR sublines with an approximately 50% decrease in DOX retention after 1 h when compared to their respective parental cell lines. Our results suggest that DOXR in LoVo/DR5 cells may result from overexpression of P-glycoprotein. In contrast, DOXR in HT1080/DR4 appears to be non-P-glycoprotein mediated and may be related to an alternative mechanism capable of altering drug efflux or differential drug binding. PMID- 2896068 TI - Characterization of the spectrum of postthymic T-cell malignancies in Taiwan. A clinicopathologic study of HTLV-1-positive and HTLV-1-negative cases. AB - Postthymic T-cell malignancy shows marked geographic, clinicopathologic, and prognostic diversity. The frequency and spectrum of T-cell malignancies in Taiwan were investigated. Fifty-two patients (35 male and 17 female) with a median age of 49 years, were consecutively encountered between October 1983 and April 1987; these accounted for 39% of non-Hodgkin's lymphoma cases seen in our institutions. Ten patients (19.3%) had adult T-cell leukemia/lymphoma (ATL) associated with human T-cell leukemia virus (HTLV-1). Patients with ATL had disease similar to that reported from southwestern Japan and the Caribbean. They had frequent skin lesions (60%), hypercalcemia (40%), and a rapid clinical course with a median survival of 1.3 years. The 35 HTLV-1-negative peripheral T-cell lymphomas (PTL) were similar to PTL in western countries, manifesting frequent visceral, cutaneous, and vascular tropisms. Marrow involvement was documented at presentation in 39% and Stage III/IV disease in 80% of the PTL patients. The histology of PTL usually expressed prominent reactive features which is distinct from that in ATL. Several subcategories could be defined: Hodgkin's-like PTL in nine patients, T-zone lymphoma in three, angioimmunoblastic lymphadenopathy-like lymphoma in one, Lennert's lymphoma in three, and angioinvasive lymphoma in four. Two HTLV-1-negative PTL had neoplastic cells with clover-shaped nuclei and were designated as ATL-like. Morphologic classification based on the modified Working Formulation showed prognostic correlation, with median survival of less than 6 months for large cell/immunoblastic PTL, compared with 5 years for patients with small/medium cell PTL. Both low- and high-grade PTL seem to represent an incurable disease. Classical cutaneous T-cell lymphoma (seven cases) is relatively unusual in Taiwan, compared with the frequency of PTL. Post-thymic T cell malignancies in Taiwan include HTLV-1-positive and HTLV-1-negative diseases, both of which have a poor prognosis and resemble similar T-cell malignancies in the East and West. PMID- 2896070 TI - [Inotropic drugs in the treatment of heart failure]. PMID- 2896071 TI - Influence of human T lymphocytes identified by antibodies to dipeptidyl peptidase IV on differentiation of human B lymphocytes stimulated with Staphylococcus aureus Cowan I and pokeweed mitogen. AB - The influence of human T lymphocytes expressing the enzyme dipeptidyl peptidase IV (DPP IV) was investigated with respect to human peripheral B-lymphocyte differentiation. B cells stimulated with pokeweed mitogen in the presence of DPP IV-positive T cells produced high amounts of immunoglobulin. Moderate amounts of immunoglobulin could be measured when B cells were cultured in the presence of DPP IV-negative T cells. DPP IV defines a T-cell subset partially overlapping the subsets characterized by the differentiation antigens Leu 3a (helper/inducer) and Leu 2a (suppressor/cytotoxic). DPP IV-positive T cells exert, in contrast to DPP IV-negative T cells, high interleukin-2 activity after stimulation with phytohemagglutinin and pokeweed mitogen. To further functionally characterize DPP IV-positive and DPP IV-negative T cells, the helper effects of Leu 3a-positive T cell subsets, differing in DPP IV expression, were investigated in pokeweed mitogen- and Staphylococcus aureus-driven B-cell differentiation systems. After pokeweed mitogen stimulation, immunoglobulin production was markedly reduced when B cells were cultured in the presence of Leu 3a-positive T cells expressing DPP IV (DPP IV+/Leu 3a+). In contrast, high amounts of immunoglobulin were produced in cultures with Leu 3a-positive but DPP IV-negative T cells (DPP IV-/Leu 3a+). This difference in immunoglobulin production of B cells cultured with DPP IV+/Leu 3a+ and DPP IV-/Leu 3a+ T cells could not be observed in Staphylococcus aureus stimulated cultures. Here, both T-cell subsets supported terminal differentiation of B cells. We conclude that in the pokeweed mitogen-driven culture systems, DPP IV+/Leu 3a+ and DPP IV-/Leu 3a+ T cells may differ in the production of growth and/or differentiation factors distinct from interleukin-2. PMID- 2896072 TI - Interactions between the Thy-1 and T-cell antigen receptor pathways in the activation of cytotoxic T cells: evidence from synergistic effects, loss variants, and anti-CD8 antibody-mediated inhibition. AB - The relationship between activation of cytolytic T-lymphocyte (CTL) clones via the T-cell receptor (Ti) or the Thy-1 molecule was investigated. Anti-Ti and anti Thy-1 monoclonal antibodies (mAb) can activate CTL clones to secrete interferon gamma (IFN-gamma). Suboptimal doses of anti-Ti and anti-Thy-1 mAb, as well as suboptimal doses of two different anti-Thy-1 mAb, can synergize to activate T cell clones. The addition of phorbol myristic acetate (PMA), which is not stimulatory by itself, can enhance the synergistic effect of mAb on IFN-gamma production. Although the Ti and Thy-1 molecules were not found associated at the cell surface, the results presented here indicate that these molecules are functionally associated. Use of Ti loss variants of a CTL clone confirms that Thy 1-mediated signaling is not an alternative to, but is dependent on the Ti mediated activation pathway. Additionally, use of anti-Lyt-2/3 mAb, previously described as interfering with class I MHC-Ti binding and/or activation and, in some cases, with anti-Ti-mediated activation revealed that anti-Thy-1 mAb mediated activation was also greatly reduced by the presence of Lyt-2/3-specific mAb. Thus the interaction between Thy-1 and Ti might also involve Lyt-2 (Lyt-3) molecules. PMID- 2896073 TI - The ATPase subunit 6 gene of tobacco mitochondria contains an unusual sequence. AB - We have isolated and characterized the F0-ATPase subunit 6 gene (atp6) from tobacco mitochondria. The tobacco sequence exists as a single copy, is transcribed and contains an open reading frame (ORF) capable of encoding a peptide of 395 amino acids. The first 130 amino acids of the tobacco putative polypeptide show limited homology with the N terminus predicted for the maize ATPase subunit 6. Although poorly conserved at the sequence level, the tobacco and maize amino termini are hydrophilic and have a high percentage of charged amino acids. This portion of the predicted peptide may represent a presequence that is common to the ATPase subunit 6 of plants. Significant homology between tobacco and maize begins with amino acid 131, in a region that is highly conserved among fungal ATPase 6 subunits. In the remainder of the predicted protein, tobacco and maize share approximately 81% homology. A 41 bp sequence and a 175 bp conserved region found upstream from the tobacco atp6 coding region are homologous with sequence elements found in the 5' flanking regions of other plant mitochondrial genes and may be important for regulation and expression of the atp6 gene. PMID- 2896074 TI - [Study on Bcl I RFLP in factor VIII gene and prenatal diagnosis of hemophilia A through RFLP]. PMID- 2896075 TI - [Undescended testicles: 2-stage reduction or Fowler's technic. Apropos of 2 comparative series]. AB - The testicular vessel transection allows a one-stage orchidopexy for high undescended testes. The authors have been using this procedure (as described by Fowler) since january 1984. 29 operations have been performed in this way. This series is compared to another series of 28 staged orchidopexies, a procedure which was used in Rouen until december 1983. The number of cases in each series is not high enough to allow a significant comparison; no conclusion can be drawn as for the long term result concerning the testicular function. However the procedure described by Fowler has the great advantage of being performed in one stage. But the surgeon must comply with strict rules and the authors point out the difficulties of the operation. PMID- 2896076 TI - Long-term effects of xamoterol on left ventricular diastolic function and late remodeling: a study in patients with anterior myocardial infarction and single vessel disease. AB - The purpose of the study was to examine whether the prolonged administration of the beta 1-adrenoceptor partial agonist xamoterol could improve left ventricular diastolic function and affect the global remodeling process of the left ventricle after anterior myocardial infarction. In 22 patients with anterior myocardial infarction and single-vessel disease, left ventricular angiography (+ Millar) was performed under basal conditions 1 to 2 months after the acute myocardial infarction. Eight patients were then treated for 3 months with placebo and 14 were treated with xamoterol (200 mg bid) and a second left ventricular angiographic study was performed. Angiograms were digitized frame by frame to derive the diastolic pressure-volume relationship and to compute wall stress. An index of elastic myocardial stiffness was computed at a constant stress of 30 kdynes/cm2 before and after treatment. To evaluate changes in left ventricular shape, segmental areas in anterior and inferior segments were computed and compared at end-diastole and end-systole. After xamoterol, left ventricular end diastolic pressure and mean diastolic wall stress decreased (from 24 +/- 5 to 15 +/- 5 mm Hg and from 57 +/- 32 to 38 +/- 22 kdynes/cm2, respectively; both p less than .01 vs baseline and vs placebo). These changes were accompanied by a downward shift in the diastolic pressure-volume relationship and by a decrease in the index of myocardial stiffness from 526 +/- 270 to 371 +/- 194 kdynes/cm2 (p less than .02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896077 TI - In situ fluorescence hybridization of Y translocations: cytogenetic analysis using probes Y190 and Y431. AB - Two moderately repetitive DNA probes (Y190 and Y431) and a fluorescent in situ hybridization technique, using a biotin, avidin, anti-avidin system, were employed to investigate a group of patients with Y chromosome abnormalities. In normal male subjects, a bright fluorescent spot could be detected in cells in interphase and on the short arm of the Y chromosome in metaphase spreads. Translocations of DNA fragments of the short arm of the Y chromosome to autosomes 10, 13 and 15 were observed in five patients. In a 45,XX male subject the translocation involved one of the X chromosomes. With this in situ hybridization procedure, bright fluorescent spots were also noticed in uncultured amniotic cells and chorionic cellular elements from male fetuses, thus allowing a rapid and reproducible approach to prenatal fetal sexing. PMID- 2896078 TI - X-linked lymphoproliferative disease: linkage studies using DNA probes. AB - Linkage studies have been carried out with 28 X-linked polymorphic probes to try to locate the gene for X-linked lymphoproliferative disease (XLP). DNA from three families has been analysed, including three affected boys among 21 family members. None of the probes tested has been found to be linked to XLP. However, the data are recorded for the use of other workers on this rare disease. PMID- 2896079 TI - Diagnosis of familial amyloidotic polyneuropathy in Sweden by RFLP analysis. AB - Genomic DNA from 17 Swedish patients with familial amyloidotic polyneuropathy (FAP), and 50 healthy controls were tested with a cDNA transthyretin probe. In seven of the patients, FAP was not reported in either of their parents. All 50 controls showed restriction fragments of 6.6 kb and 3.2 kb after cleavage with Nsil, while the 17 FAP patients showed RFLP markers of 5.1 and 1.5 kb. These observations indicate the same methionine for valine substitution at position 30 in Swedish patients with FAP as seen in patients with FAP from Japan, Portugal and FAP-patients of Swedish descent from USA. However, the mean onset of FAP symptoms for the 17 Swedish patients was found to be significantly later than for the patients from Japan, Portugal and USA. PMID- 2896080 TI - Effect of almitrine bismesylate on breathing pattern during hypoxia/hypercapnia in rats and ferrets. AB - 1. Ventilatory measurements and functional residual capacity (FRC) were recorded from anaesthetized rats and ferrets using a whole body plethysmograph. Simulation of aspects of human chronic obstructive airways disease (COAD) was attempted by making animals acutely hypoxic or hypoxic and hypercapnic by causing them to breath appropriate gas mixtures or by increasing the tracheal resistance or dead space. Some chronically hypoxic rats, which have muscularized pulmonary arterioles similar to COAD patients, were also studied. 2. In 18 chronically hypoxic (CH) rats and 17 littermate control rats (C), breathing air, doses of almitrine bismesylate caused greater increases in ventilation (VE) in C than in CH rats. FRC, which was initially greater in CH rats, increased significantly in both groups after almitrine. 3. In C rats, breathing hypoxic or hypoxic/hypercapnic gas mixtures caused large increases in VE. Slow infusions of almitrine caused a further increase in VE usually via an increase in tidal volume (VT) but not frequency (f). 4. In two series of rats (n = 9; n = 6) severe and moderate degrees of tracheal obstruction caused a fall in PaO2 and a rise in PaCO2, a fall in VE due to both VT and f and large changes in oesophageal pressure (Poes), which often became positive on expiration. Almitrine infusions usually caused a rise in PaO2, a rise in VT and no change in f; with moderate obstruction, Poes also rose. The results were thought to depend on the balance between improved ventilation and increased O2 demand of the respiratory muscles. 5. Eleven ferrets were made hypoxic and hypercapnic by adding a large dead-space to the trachea. A slow infusion of almitrine caused a significant rise in PaO2 before any significant change in VE was detected; PaCO2 fell at some time during the infusion, but not significantly. The initial significant rise in PaO2, at 2.5 min, was not associated with significant changes in T1 (time of inspiration) and VT/TI. At 5 min VT/TI and PaO2 were all significantly altered. 6. Infusions of almitrine into hypoxic and hypercapnic animals caused improvements in the arterial oxygen tension which were associated with subtle changes in the breathing pattern; inspiratory time and inspiratory flow rate changed in the absence of an increase in total VE. Possible conclusions with respect to the action of almitrine in patients with COAD are discussed. PMID- 2896081 TI - The effect of the carotid sinus reflex on large coronary artery diameter in anaesthetized dogs. AB - 1. The diameter of, and blood flow in, the left circumflex coronary artery was measured in anaesthetized dogs and the carotid sinus reflex was stimulated by bilateral occlusion of the carotid arteries (BCO) for 2 min. 2. The effect of BCO on coronary artery diameter and late diastolic coronary resistance was examined: (a) after bilateral vagotomy; (b) after vagotomy plus antagonism of beta adrenoceptors with propranolol (1 mg/kg, i.v.); and (c) after vagotomy, antagonism of beta-adrenoceptors and antagonism of alpha-adrenoceptors with phentolamine (0.5 mg/kg, i.v.). 3. After vagotomy BCO increased mean arterial pressure (delta = 72 +/- 7 mmHg), heart rate (16 +/- 3 beats/min), coronary blood flow (37 +/- 11 ml/min) and coronary artery diameter (0.14 +/- 0.04 mm). Late diastolic coronary resistance initially fell (-0.26 +/- 0.13 mmHg min/ml at 30 s) but at the end of the 2 min occlusion it had returned to the baseline level (delta = 0.04 +/- 0.08 mmHg min/ml). 4. In the presence of propranolol BCO increased arterial pressure (28 +/- 12 mmHg), but did not alter heart rate (0.6 +/- 0.4 beats/min) or coronary blood flow (2 +/- 2 ml/min). There was a significant decrease in large artery diameter (-0.24 +/- 0.07 mm) and an increase in late diastolic coronary resistance (0.46 +/- 0.12 mmHg min/ml). A mechanical increase in afterload did not affect large coronary artery diameter or coronary resistance. 5. Antagonism of alpha-adrenoceptors abolished the reflex-induced constriction of the large coronary artery (delta = -0.02 +/- 0.02 mm) and the coronary resistance vessels (delta LDCR = -0.02 +/- 0.03 mmHg min ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896082 TI - The alpha 2-adrenoceptor agonists clonidine, TL99 and DPI enhance vasoconstrictor responses to sympathetic nerve stimulation and noradrenaline in the rat tail artery preparation. AB - 1. Clonidine (1-30 nmol/l) enhanced the vasoconstrictor responses to sympathetic nerve stimulation in isolated perfused artery preparations from the rat tail. Higher concentrations of clonidine produced vasoconstriction in most artery preparations and reduced the response to sympathetic nerve stimulation. 2. The enhancing effect of clonidine was not affected by prazosin but was blocked by idazoxan, indicating that it was due to activation of alpha 2-adrenoceptors. 3. The alpha 2-adrenoceptor agonists DPI and TL99, like clonidine, enhanced vasoconstrictor responses to sympathetic nerve stimulation. 4. Vasoconstrictor responses to noradrenaline were enhanced by clonidine and TL99. 5. The findings suggest that activation of postjunctional alpha 2-adrenoceptors results in facilitation of the contractile response elicited by activation of alpha 1 adrenoceptors. PMID- 2896083 TI - The effect of antipyrine and rifampicin on the excretion of renal enzymes in human urine. AB - Two well-known drugs that induce the liver microsomal enzyme system in man were administered to 3 different groups of healthy male volunteers. Antipyrine 1200 mg and rifampicin in two different doses of 600 mg or 1200 mg daily were given orally to each group over a period of seven days. The extent of liver microsomal enzyme induction was assessed by estimating antipyrine elimination, serum gamma glutamyl-transferase (GGT) activity and the urinary excretion rate of 6-beta hydroxycortisol. In addition, possible effects on renal enzymes were monitored by measuring gamma-glutamyltransferase (GGT) and beta-glucuronidase (GRS) urinary excretion rates before and after drug administration. The possibility of a direct toxic effect on the renal tubular epithelium following drug administration was assessed by the measurement of urinary beta-N-acetylglucosaminidase (AGS) activity, total protein and glucose. Antipyrine plasma clearance and 6-beta-OHF excretion rates increased significantly in the groups treated with antipyrine or rifampicin, while serum GGT activities were enhanced only following antipyrine. Antipyrine administration increased urinary GGT excretion both immediately and one week after cessation of drug administration, but no changes were found following the administration of rifampicin. GRS, AGS, total protein and glucose excretion in urine remained unchanged during and after the administration of each individual drug. Based on these findings, the increased urinary GGT excretion observed following antipyrine treatment may be due to an inducing effect on the renal tubular cells, as no evidence for a toxic renal damage was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896084 TI - Altered balance in the autonomic nervous system in schizophrenic patients. AB - The aim of the present study was to evaluate the autonomic nervous function in schizophrenic patients. Twenty-eight patients (29 +/- 6 years) diagnosed as schizophrenics and in stable medication were included, together with ten schizophrenic patients (25 +/- 5 years) who were unmedicated. Eleven healthy subjects (32 +/- 7 years) served as controls. Immediate heart-rate responses to a single deep inspiration was used as a measure of parasympathetic function. Heart rate response to standing was used as a measure of sympathetic function. Supine blood pressure, heart-rate and orthostatic changes in blood pressure did not differ between groups. Heart-rate response to standing was greater in both medicated and non-medicated schizophrenics compared to normal subjects (P less than 0.01). Heart-rate response to standing was greater in non-medicated compared to medicated schizophrenics (P less than 0.05). Heart-rate response to inspiration was greater in non-medicated schizophrenics compared to normal subjects (P less than 0.05), whereas no difference was found between medicated and non-medicated schizophrenics. The results show that the balance in the autonomic nervous system is altered in schizophrenic patients with a hyperexcitability in both the sympathetic and the parasympathetic division. Our study has thus indicated a dysfunction in the autonomic nervous system per se and the previous interpretations of attentional orienting responses in schizophrenia is questioned. Medication with neuroleptics seems to partly normalize the autonomic reactivity rather than being the cause of autonomic dysfunction. PMID- 2896085 TI - Leukemias and lymphomas of thymic differentiation. AB - Neoplasms of thymic T-cell derivation include two closely related malignancies: T cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma. The recognition of these tumors as distinct biologic entities dates back to the early 1970s, when patients with these diseases were found to have tumor cells that formed spontaneous rosettes with sheep erythrocytes. In the last decade, however, the growth of new technologies and availability of new reagents has enabled us to characterize this group of diseases with more precision. When studied with a panel of monoclonal antibodies, there is tremendous phenotypic diversity in the types of T-cell leukemias that are encountered. In spite of this diversity, a few general facts have become apparent. To a first approximation, thymic T-cell malignancies can be related to stages of normal T-cell development. Surprisingly, in spite of the overall similarity between T-ALL and T-lymphoblastic lymphoma, the antigenic phenotypes encountered suggest a biologic difference between these two diseases. Although there is not currently any single reagent that permits recognition of T-ALL or lymphoblastic lymphoma in all cases, a combination of technologic approaches using conventional morphology and histochemistry, immunologic studies, and, in some cases, newer genetic studies should permit great precision in the definition of this disease. The clinical picture of T-cell ALL or lymphoblastic lymphoma has traditionally been one of a poor prognosis disease with high WBC count, bulky adenopathy, and mediastinal mass. Although encountering this clinical presentation should suggest the T-cell phenotype, not all patients with T-cell leukemia will fit this stereotype. Clinical studies have also served to provide support for the expanding biologic definition of T-cell neoplasia, particularly insofar as it has been demonstrated that patients with T antigen-positive but E rosette-negative ALL behave like other patients with T cell disease. In short, patients with thymic T-cell malignancies not only have distinctive biologic characteristics to their blasts, but also have a distinctive pattern of clinical presentation, response to therapy, and sites of relapse. These differences have prompted the search for specific therapies and also directed approaches to understanding the variable clinical outcome of patients with these malignancies. PMID- 2896086 TI - T-cell lymphomas and leukemias of post-thymic differentiation. AB - This article describes the heterogeneity of post-thymic T-cell malignancies and correlates specific clinicopathologic entities with morphology and immunophenotype. Peripheral T-cell lymphomas are subclassified into six main histologic types with different prognoses. Special attention is given to the theme of proposed origin and spread of T-cell malignancies. PMID- 2896087 TI - Immunobiology of malignant B cells and immunoregulatory cells in B-chronic lymphocytic leukemia. AB - This article reviews pertinent immunobiologic features of the malignant B cell and the circulating immunoregulatory cells (T and NK) that characterize B-CLL. PMID- 2896088 TI - Clinical and molecular parameters of HTLV-I infection. AB - The elucidation of the spread of HTLV-I through high-risk groups and the finite but real incidence of HTLV-I seropositivity in normal blood donor populations in the United States indicates that blood and blood products should be screened for this infectious agent. Because of the ability of the provirus to exist in a quiescent state and the long lag time between exposure and seroconversion, it may be necessary to screen potential blood donors for integrated sequences by gene amplification methodologies in addition to standard serologic testing to protect the blood supply. The detection of the HTLV-I virus often requires multiple modes of testing, even in ATL patients. We have characterized by gene amplification several HTLV-I positive lymphoma patients who were seronegative. We have also identified by radioimmunoprecipitation assays intravenous drugs abusers who have antibody solely to the nuclear pX gene product and who do not, therefore, test positive in an ELISA assay prepared from purified virion proteins. All HTLV-I positive patients need to be counseled about the biohazard status of their body fluids. The fact tha only 1 to 2 per cent of HTLV-I infected persons have any diagnosable disease, coupled with the knowledge that the mean time for the onset of clinical manifestations is some 20 to 30 years following conversion to seropositivity, indicates that this is not a virulent pathogen or a highly transforming virus. These epidemiologic data support the notion of HTLV-I's role as a mitogen or first lesion in a multistep pathway to malignancy. These data are also consistent with the idea of rare random cis-activation of one of many cellular oncogenes following a fortuitous integration event. PMID- 2896089 TI - Studies on the energy metabolism of opossum Didelphis virginiana erythrocytes- II. Comparative aspects of 2-deoxy-D-glucose catabolism in opossum and human red cells in vitro. AB - 1. G-6-P, F-6-P, F-1, 6-P, DHAP and GA-3-P in opossum erythrocytes were found at levels above those reported in human red cells. 2. About 1% of the radioactivity provided as [1-14C] DOG to red cells of both species was recovered as 14CO2 in 1 hr. 3. Unlike [1-14C] DOG, radiochromatography of extracts of cells incubated DOG revealed two diffusible radiolabelled compounds in the supernatant of cell suspensions. 4. The catabolism of DOG was quantitatively and qualitatively similar in opossum and human erythrocytes under the conditions of this study. PMID- 2896090 TI - Studies on the energy metabolism of opossum Didelphis virginiana erythrocytes- III. Metabolic depletion with 2-deoxyglucose markedly accelerates methemoglobin reduction in opossum but not in human erythrocytes. AB - 1. Glucose-depleted, nitrite-treated erythrocytes reduce ferriheme in vitro in an environment 100 mM to 2-deoxy-D-glucose at a rate of 2.4 microM/ml cells/hr (opossum) and 0.37 microM/ml cells/hr (human). 2. During the process of methemoglobin reduction the breakdown of adenine ribonucleotides is more rapid in opossum (0.9 microM/g hg/hr) than in human (0.36 microM/g hg/hr) erythrocytes. 3. Radiolabelled ribose from [U-14C] ATP is catabolized exclusively to [14C] lactate in opossum, and to [14C] pyruvate and [14C] lactate in human red cells. PMID- 2896091 TI - Long-term cold adaptation in the rat. AB - 1. To determine whether long-term cold exposure induces insulative adaptation in the rat, two groups of eight adult animals each were exposed to 4 and 25 degrees C, respectively, for 18 months. 2. At any ambient temperature between -5 and 30 degrees C, the cold adapted animals had a higher rate of oxygen uptake, and higher unfurred skin temperatures than the controls. 3. At ambient temperatures below thermoneutrality, whole body thermal resistance increased continuously in both groups of animals. 4. It is concluded that long-term exposure does not induce insulative adaptation, and that thermal resistance is not maximal at the lower critical temperature. PMID- 2896092 TI - Cytoskeletal control of calcium absorption across the rat small intestine. AB - 1. The effect of colchicine, cytochalasin-B and procaine on calcium transport across the rat small intestine was investigated. The results obtained show the following: 2. Colchicine and cytochalasin-B at different concentrations inhibited significantly (P less than 0.001) calcium accumulation in rat intestinal cells, whereas procaine at different concentrations increased significantly (P less than 0.001) calcium accumulation in the rat small intestine. 3. Unidirectional influx of calcium across the rat small intestine was significantly inhibited (P less than 0.01) in the presence of colchicine and cytochalasin-B in the preincubation medium. Procaine, on the other hand, caused a significant increase (P less than 0.01) in the unidirectional influx of calcium across the rat intestinal cells. 4. The cell water content was not altered in the presence of the different drugs indicating that the changes in calcium transport across the rat intestinal cells are not due to alterations in the structure of the cell membrane. PMID- 2896093 TI - Bile acids from the harp seals, Phoca groenlandica. AB - 1. The bile acids composition of the harp seal, Phoca groenlandica, collected around Newfoundland, Canada, had been examined. 2. 13C n.m.r. spectroscopy of the crude bile extract was superior to t.l.c. analysis in revealing the presence of phocaecholic acid and a taurine moiety in this mixture. 3. The relative percentage of cholic, phocaecholic and chenodeoxycholic acids was 60.5% (+/- 4.5), 21.4% (+/- 4.0) and 18.1% (+/- 5.8), respectively. 4. The variation in the percentage of bile acids did not correlate with the sex of the sampled animals, but varied significantly with the age of the seals. PMID- 2896094 TI - Voluntary regulation of energy balance in farmed raccoon dogs. AB - 1. Seasonal changes in body mass and voluntary feed intake were studied in juvenile raccoon dogs (Nyctereutes procyonoides, Gray 1834) under farm conditions. 2. The body weight maximum was achieved in mid-November. Thereafter, body weight gradually declined towards summer. This pattern was closely connected to voluntary regulation of feed consumption. During autumn, appetite of the animals was good enhancing gradual deposition of excessive fat reserves. 3. Excessive adiposity itself, together with factors like shortening daylength and decreasing air temperature, seemed to play as a trigger for starting of winter rest. 4. The results support the endogenic nature of energy balance regulation. PMID- 2896095 TI - Remote controlled sampling of cattle and buffalo blood. AB - 1. Blood samples were obtained from cattle and buffaloes over extended periods of time by remote controlled methods at 4-hourly intervals. 2. Initial handling of the animals and deliberate exposure to stress at the end of the experimental times resulted in increased plasma concentrations of a number of variables. 3. Between initial handling and applied stress, the concentration of all variables investigated showed little change and no evidence of rhythms. 4. The results obtained reflect true plasma composition of free ranging cattle and buffaloes at rest. PMID- 2896096 TI - Species variations of somatostatin concentrations and binding sites in jejunal mucosa. AB - 1. Somatostatin-like immunoreactivity (SLI) and specific binding of 125I-Tyr11 somatostatin were measured in jejunal mucosa of the mouse, rat, hamster, rabbit and guinea-pig. 2. The SLI concentrations in guinea-pig and rabbit were much greater than those in other rodents considered. 3. Somatostatin binding varied greatly with the species examined, the highest values being observed in cytosolic fraction of guinea-pig and rabbit jejunal mucosa, but the lowest ones in mouse. 4. The observed differences in somatostatin binding were not related to varying extents of degradation by the diverse cytosolic preparations studied. 5. The binding sites were highly specific for somatostatin in all rodent species studied. 6. There appears to be a direct relationship between somatostatin levels and somatostatin binding sites in jejunal mucosa when considering a variety of rodent species usually employed as laboratory animals. PMID- 2896097 TI - Influence of adrenalectomy on age-related changes in energy balance, thermogenesis and brown fat activity in the rat. PMID- 2896099 TI - A new non-hormonal antifertility drug DL-204: II. Effect on testicular hyaluronidase and gamma-glutamyl transpeptidase in male rats. AB - Effects of DL-204, 2-(3-ethoxyphenyl)-5,6-dihydro (5,1-a)-isoquinoline, a non hormonal antifertility drug on testicular hyaluronidase and gamma-glutamyl transpeptidase levels, biochemical markers for testicular function, were evaluated in male rats. Treatment of 21-day-old rats with DL-204 for 7 or 15 days produced cryptorchid condition. Testicular hyaluronidase and gamma-glutamyl transpeptidase levels reveal that DL-204 acts on the testes, possibly in two ways; one, by reducing the gonadotropin levels thereby reducing the levels of androgens as reflected by reduced accessory reproductive organ weights and, secondly, by a direct action on the testes. Thus, we conclude that DL-204 is acting as an antispermatogenic agent, possibly acting in more than one way on the testes. PMID- 2896098 TI - A technique for the in vitro incubation of deer antler tissue. AB - 1. A procedure for the in vitro incubation of velvet deer antler tissue was developed. Biopsy samples were collected in June with a trephine from 2 adult white-tailed deer and incubated in modified BGJb medium up to 48 hr. Calcium (Ca) and hydroxyproline (OH-proline) concentrations in the tissue were determined. 2. A significant increase (P less than 0.05) in Ca was exhibited at 4 and 8 hr of incubation, and, after replenishment of media, at 48 hr. 3. Hydroxyproline concentrations continued to rise throughout the duration of the incubation period and were significantly higher than controls (P less than 0.05) at 16, 24, and 48 hr. 4. Results suggest antler tissue can be incubated in vitro with the protocol described, although length of incubation may vary with parameter measured. PMID- 2896100 TI - Characterization of alpha 2-adrenergic receptors, negatively coupled to adenylate cyclase, in rabbit ciliary processes. AB - Inhibition of ciliary process adenylate cyclase was studied on rabbit membrane preparations. When considered individually, epinephrine, GTP and NaCl did not inhibit adenylate cyclase activity. On the other hand, when present together, epinephrine, GTP (10(-5) M) and NaCl (200 mM) acted synergistically to cause a 27% inhibition of basal activity. A similar inhibition was observed with 1 norepinephrine. Clonidine and BHT 920, two alpha 2-agents were found to be partial agonists causing 63% and 82% as much inhibition as epinephrine. Phenylephrine, an alpha 1-agonist did not inhibit adenylate cyclase activity at concentrations up to 10(-4) M. Yohimbine and phentolamine prevented the inhibition of adenylate cyclase by epinephrine, while prazosin was ineffective. Alpha 2-receptor selectivity in rabbit ciliary processes and their negative coupling to an adenylate cyclase via a NaCl-dependent GTP binding protein, Ni, is thus well established. PMID- 2896101 TI - The role of somatostatin and serotonin in the beta-adrenoceptor regulation of gastric function. An experimental study in dogs. AB - CHAPTER 1. The gastric functions are regulated in a complex manner by the autonomic nervous system, sympathetic and parasympathetic, and hormones and moreover by a system of peptide-containing cells and nerves. The sympathetic influence is mediated by alpha- and beta-adrenoceptors, beta-adrenoceptor agonists in general inhibit the gastric functions. The effects of the beta adrenoceptors are probably mediated indirectly, and the responsible mechanism may be via release of and endogenous mediator--somatostatin or serotonin. The purpose of the present study, described in the survey, is to examine whether somatostatin or serotonin acts as a mediator for the gastric effects in vivo of beta adrenoceptor agonists. The proposed mediator must present the following characteristics: A. Inhibitory effects of "physiological" doses in vivo. B. Inhibitory characteristics similar to those of the beta-adrenoceptor agonists. C. A beta-adrenoceptor mediated release. CHAPTER 2. In this chapter the known effects of beta-adrenoceptor agonists on gastric functions (acid secretion, pepsin secretion, antral motility and mucosal blood flow) are presented. The possible mechanisms mediating these effects are mentioned, and the effects of somatostatin and serotonin are reviewed. Beta-adrenoceptor agonists inhibit the acid secretion in vivo in several species, but stimulate in vitro. A similar pattern is probable as for the pepsin secretion, but sufficient results are not available in order to draw a certain conclusion. The antral motility is inhibited both in vivo and in vitro. The mucosal blood flow is increased compared to the acid secretion, however the results points to variable effects depending on the circumstances of the experiments. On the basis of the reviewed effects of somatostatin it is concluded that the effects are inhibitory, but the inhibitory characteristics are not known. A beta-adrenoceptor mediated release of somatostatin has been found, but it has not been examined selectively for the stomach. The gastric effects of serotonin has been sparsely examined and it is not possible to determine the effects as parts of a certain characteristic. It is concluded that neither somatostatin nor serotonin have been examined sufficiently to determine which is the proposed mediator. CHAPTER 3. The materials and methods used are reviewed. Dogs were used and various parameters were measured--acid secretion by titration, pepsin secretion by enzymatic process with haemoglobin as substrate, antral motility by registration of intraluminal pressure, mucosal blood flow by the clearance of neutral red, somatostatin by radioimmunoassay.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2896102 TI - Increased myocardial contractility following growth hormone administration in normal man. An echocardiographic study. AB - Cardiac function was studied by echocardiography in 11 normal subjects before subcutaneous growth hormone administration (first control), after one week of subcutaneous growth hormone administration and at one week after stopping subcutaneous growth hormone administration (second control). Plasma growth hormone was 1.4 ng/ml and 4.5 ng/ml, respectively, at the first two examinations. Compared to the first and second control situations heart rate increased by 9% (p less than 0.1) and 15% (p less than 0.01), fractional shortening of the left ventricle by 8% (p less than 0.02) and 9% (p less than 0.01), and mean circumferential shortening velocity by 10% (p less than 0.05) and 14% (p less than 0.01) respectively. Mean arterial blood pressure was unchanged. Thus, in normal man an increase in plasma growth hormone up to levels comparable to those seen in type 1 diabetics during conditions of poor metabolic control seems to be followed by enhancement in myocardial contractility. Therefore we suggest that growth hormone might contribute to the increase of myocardial contractility earlier described in type 1 diabetic patients with no clinical signs of microvascular disease. PMID- 2896103 TI - Platypnea induced by worsening of VA/Q inhomogeneity in the sitting position in chronic obstructive lung disease. AB - We report a patient with COPD who experienced severe dyspnea with a decreased PaO2 in the sitting position, largely improved in the ventral prone position (platypnea). By using an isotopic method, we showed that this phenomenon is the result of a deleterious effect of the sitting position on regional ventilation/perfusion matching. We speculated that hypoxic vascular pulmonary constriction was deficient in our patient. This hypothesis is supported by a dramatically better matching of the VA/Q ratio after treatment with almitrine bismesilate, a drug that could potentiate hypoxic pulmonary vasoconstrictive reflexes. PMID- 2896104 TI - The effect of azelastine on exercise-induced asthma. AB - In ten young asthmatic subjects, we studied the effect of a single oral dose of 4.4 mg of azelastine hydrochloride on exercise-induced bronchoconstriction during the breathing of cold air. Exercise challenges were performed on two different days before and four hours after azelastine and placebo given in a randomized double-blind crossover fashion. Placebo had no effect on baseline pulmonary function and postexertional obstruction of the airways, in contrast to azelastine, which exerted a small but significant (p less than 0.05) bronchodilation and a significant attenuation (p less than 0.01) of exercise induced bronchoconstriction as compared to data from before treatment and after placebo. PMID- 2896105 TI - Pharmacodynamic aspects of chlorpheniramine-induced bronchodilatation. AB - In 12 asthmatic (A) and ten normal (N) subjects, we measured the effect of inhaled saline solution, acetylcholine, histamine (H), and chlorpheniramine (CP) on specific airway conductance and forced exploratory flows. We found that CP dilated the bronchi in six asthmatic patients and one normal subject by acting on bronchial H1 receptor. This action is also modulated by the abnormal functions of this receptor-transducer, explaining why CO exerts a tonic effect only in subjects with H hyperresponsiveness. Furthermore, as shown by CO and CP + H responses, bronchial histamine seems to be present primarily in large airways and in relatively small amounts. We also found that bronchial H, the abnormal H1 receptor-transducer, and the bronchial caliber are regulated independently of each other. Consequently, this limits the therapy with H1 blockers in asthma. PMID- 2896106 TI - Serum ferritin in normal subjects and in some diseases. PMID- 2896107 TI - Renal damage in hemorrhagic fever with renal syndrome. Measurements of urine and serum lysozyme and urine IgG. PMID- 2896108 TI - [Isolation of the black pigmented Bacteroides from the subgingival plaque of adult patients with periodontitis]. PMID- 2896109 TI - Alzheimer's disease as an age-dependent disorder. AB - Alzheimer's disease is the most significant of the age-related diseases of the brain. The incidence of Alzheimer's at age 80 is twenty-fold that at age 60 years. In one study the incidence at age 80 surpassed that of stroke. Three major advances have occurred in regard to Alzheimer's disease: (1) clinical diagnosis has markedly improved and now approaches 90% accuracy; (2) understanding of the biology of Alzheimer's has increased with delineation of specific fibrous protein abnormalities and identification of the amyloid precursor gene and the gene linked to familial Alzheimer's, both genes being located on chromosome 21; and (3) there have been advances in the correlation of specific nerve cell involvement and neurotransmitter changes with physiological (position emission tomography), behavioural and neuropsychological manifestations. PMID- 2896110 TI - [Malignant syndromes due to psychotherapeutic agents]. PMID- 2896111 TI - Cyclosporin A does not inhibit the PHA-stimulated increase in intracellular Ca2+ concentration but inhibits the increase in E-rosette receptor (CD2) expression and appearance of interleukin-2 receptors (CD25). AB - The immunosuppressive drug cyclosporin A (CsA) inhibits mixed lymphocyte responses, blocks the generation of cytotoxic T lymphocytes, and inhibits the T lymphocyte proliferative response stimulated by polyclonal activators such as phytohemagglutinin (PHA). Nevertheless, there have been contradictory reports attempting to explain the mechanism(s) for this immunosuppressive activity. In the current studies, human peripheral blood mononuclear cells (PBM) were stimulated with PHA in the presence or absence of CsA. Flow cytometric examination of PBM loaded with the Ca2+-sensitive dye Indo-1 showed that concentrations of CsA sufficient to inhibit 90-100% of tritiated thymidine incorporation had no effect on the PHA-stimulated increase in the intracellular Ca2+ concentration ([Ca2+]i). Likewise, inhibitory amounts of CsA had virtually no effect on the increase in cell volume that occurs during T lymphocyte activation. These results were not altered by pretreating the PBM with CsA for 30 min at 37 degrees C prior to adding the PHA. On the other hand, inhibitory concentrations of CsA prevented the expression of receptors for T cell growth factor (interleukin-2, IL-2), as measured by monoclonal antibodies to CD25 after 16-24-hr incubation. In like manner, CsA also prevented the increase in the expression of the E-rosette receptor (CD2) on these same cells. If cultures containing PHA and inhibitory amounts of CsA were incubated for 40-72 h, there was partial recovery both of proliferative activity and of the expression of CD25 and CD2. Thus, CsA does not appear to affect the initial activation signal(s), but does interfere with one or more subsequent events necessary to initiate the appearance of "activation antigens." PMID- 2896112 TI - Congenital hypertrophy of the retinal pigment epithelium as a marker for familial adenomatous polyposis. AB - Fifty patients were assessed for congenital hypertrophy of the retinal pigment epithelium (CHRPE) as a potential phenotypic marker for familial adenomatous polyposis (FAP), with and without other extracolonic manifestations (ECM). The ocular anomaly, which characteristically is multiple, benign, and congenital, was studied in three groups. Group 1 contained eight patients with nonpolyposis colon cancer as disease controls. All had negative eye findings. Group 2 included 40 patients with FAP, 35 (87.5 percent) of whom had retinal lesions. Twenty-two of 25 patients with FAP alone had retinal lesions while 13 of 15 patients with FAP and extracolonic manifestations were similarly affected. Group 3 included 11 offspring at risk for FAP. Eight (72.7 percent) offspring had retinal lesions. One of the eight subjects with the ocular trait was subsequently diagnosed with FAP. Two of the eight patients also had other ECM but have not been sigmoidoscoped for FAP. Seven of 11 offspring (mean age, 12.5 years) have had negative flexible sigmoidoscopy. Specificity of the retinal lesions in FAP cannot be ascertained until subsequent adenomas are identified on follow-up of the group at risk. The gene responsible for CHRPE appears to be transmitted from one generation to another, demonstrated by the high sensitivity of the retinal lesions in patients with FAP alone and with other ECM. PMID- 2896113 TI - [The importance of Entamoeba histolytica in persons returning from the tropics]. AB - Stools from 1000 travellers returning from the tropics were examined for intestinal parasites. The most frequently isolated intestinal pathogens were Giardia lamblia (5%) and E. histolytica (3.6%). For 21 out of 36 E. histolytica isolates iso-enzyme differentiation by starch-gel electrophoresis was possible, yielding a pathogenic pattern in four. This finding correlated closely with clinical symptoms and positive serology, while E. histolytica with non-pathogenic zymodeme should not be considered as a cause of diarrhoea. PMID- 2896114 TI - Comparative clinical trial of two injectable NSAIDs, tiaprofenic acid and alclofenac, in acute sciatica. PMID- 2896115 TI - [Clinical relevance of the determination of TSH-binding inhibitory immunoglobulins (TBII) in patients with immunogenic hyperthyroidism in methimazole therapy]. AB - In 38 patients with immunogenic hyperthyroidism a follow-up was performed to estimate the value of TBII before, during and after methimazole therapy. Before therapy increased TBII were detectable in 37 patients (94.4%). After 12 months methimazole therapy 25 patients had TSH-receptor antibodies (66%) within the normal range. In 13 patients positive antibody titres were found. In most cases persistence of increased TBII-values during drug treatment was an indicator of the persistence of active hyperthyroidism (10 of 13 patients). In the rule a disappearance of TBII-activity was combined with a functional remission (22 of 25 patients). Prolonged demonstration of TBII-activity in conjunction with persistence of hyperthyroidism should lead to ablative measures. In contrast to this medical therapy should be finished in patients with immunological and functional remission. Though in the further follow-up a recurrence of the immunological base of the disease with a functional and clinical relapse is possible. PMID- 2896116 TI - [ST elevation in the initial phase of myocardial infarct--a sequela of acute coronary occlusion of an expression of neurohumorally-induced metabolic processes?]. AB - The artificial coronary artery occlusion results immediately in ST-segment elevation (ST-E), therefore the ST-E in acute myocardial infarction is considered to be the result of acute coronary occlusion. But in the early phase of myocardial infarction a significant correlation between ST-E and occlusion of the coronary artery does not exist. The early ST-E seems to be predominantly the consequence of sympathico-adrenergic induced metabolic processes in the ischemic myocardium. The beta receptor blockade during the first 90 minutes after the onset of infarction decreased the ST-E by 73 +/- 6% within one hour. Treatment with beta receptor blockers in the acute phase in all patients with first anterior wall infarcts accompanied with ST-E leads to a favorable prognosis. Early ST-E can therefore be considered as a sign of sympathico-adrenergic induced changes in myocardial metabolism. Thus the beta receptor blockade in the acute phase (of anterior wall infarctions) seems to be therapeutically indicated. PMID- 2896117 TI - Effect of withdrawal of somatostatin and growth hormone (GH)-releasing factor on GH release in vitro. AB - The secretion of GH, in vivo, is pulsatile. We have proposed that the timing of the episodic bursts of GH secretion is set by somatostatin (SRIF) withdrawal, while the magnitude of the bursts is set by the amount of GH-releasing factor (GRF) impinging on the somatotrophs, before and during SRIF withdrawal. We have now used an in vitro model of perifused rat pars distalis cells to further examine the interaction between GRF and SRIF on the magnitude of the burst of GH release that follows SRIF withdrawal. We first characterized the GH response, with time, to constant perifusion with GRF. The initial burst, followed by a rapid decrease in GH release induced by constant perifusion is due to a loss of GRF bioactivity in the perifusion medium and not to a decreasing responsiveness of the somatotrophs. This was followed by studies on the interaction between GRF and SRIF. The burst of GH release after cessation of perifusion with SRIF (10(-9) M) plus GRF (10(-10) M) can be blocked by the administration of SRIF during the burst. Also, the magnitude of the burst is proportional to the concentration of GRF preceding the withdrawal of SRIF. It is likely that similar relations apply in vivo, where SRIF withdrawal sets the timing and duration of the episodic burst of GH release, while GRF sets the magnitude. PMID- 2896118 TI - Primary structures of somatostatins from the islet organ of the hagfish suggest an anomalous pathway of posttranslational processing of prosomatostatin-1. AB - The cyclostomes represent the first class of vertebrate in evolution to develop an endocrine pancreas. Two peptides with somatostatin-like immunoreactivity were isolated from the islet organ of one such cyclostome, the Atlantic hagfish (Myxine glutinosa). The primary structure of the more abundant peptide was established as: Ala-Val-Glu-Arg-Pro5-Arg-Gln-Asp-Gly-Gln10-Val-His-Glu-Pro- Pro15 Gly-Arg-Glu-Arg-Lys20-Ala-Gly-Cys-Lys-Asn25-Phe- Phe-Trp-Lys-Thr30-Phe-Thr-Ser Cys. The second peptide, comprising 27% of the total immunoreactivity in the islet extract, was identical to mammalian somatostatin-14. The pathway of posttranslational processing of prosomatostatin in the hagfish islet differs markedly from the pathway in the higher vertebrates. In the mammalian pancreas, prosomatostatin is cleaved at the site of the single arginyl residue (corresponding to position 6 in hagfish somatostatin-34) and at the arginine lysine site (corresponding to positions 19 and 20 in the hagfish peptide) to generate somatostatin-14 and somatostatin-28(1-12)-peptide. In the hagfish islet, Arg6 is not used as a cleavage site and cleavage at Arg19-Lys20 represents only a minor pathway of processing. The data provide further evidence of the strong evolutionary pressure to conserve the complete amino acid sequence of somatostatin-14. PMID- 2896119 TI - In vitro regulation of growth hormone (GH) release from ovine pituitary cells during fetal and neonatal development: effects of GH-releasing factor, somatostatin, and insulin-like growth factor I. AB - Using a monolayer approach, we have examined the acute (3 h) effects of GRF, somatostatin (SRIF), and insulin-like growth factor I (IGF-I) on GH release from pituitary cells of male and female 70-, 100-, and 130-day-old fetuses and newborn lambs and of prepubertal male lambs. GRF stimulated basal GH release in a dose dependent (10(-12)-10(-8) M) manner at each stage in development. There was no linear relationship between maximal response and increasing age of the donor animals. The ED50 values for GRF were similar in all groups, except in the pituitaries from male and female 130-day-old fetuses, where the ED50 values were significantly higher. SRIF elicited a dose-related (10(-10)-10(-6) M) inhibition of basal GH secretion at each stage of fetal life and in the prepubertal period; although the response was lower in the youngest fetal pituitaries, there was no significant change in maximal response during the fetal or prepubertal period. No effect of SRIF on basal GH secretion was observed in newborn lambs. However, SRIF (10(-7) M) was able to block GRF (10(-8) M)-stimulated GH release in 100- and 130 day-old fetal and prepubertal as well as newborn lamb pituitary cells. Plasma IGF I concentrations increased from 15.0 +/- 0.7 (mean +/- SE) and 13.8 +/- 0.9 ng/ml for male and female animals, respectively, at 70 days gestation to 55.8 +/- 3.2 and 51.8 +/- 11.1 ng/ml at the time of birth. The increase was much more pronounced in prepubertal lambs, especially in male animals, where IGF-I levels reached 300.8 +/- 37.7 ng/ml. IGF-I (100 ng/ml) had no effect on basal GH release in 70- and 100-day-old fetal, newborn, and prepubertal lamb pituitary cultures, but significantly inhibited basal GH secretion from 130-day-old fetal cells. This dose of IGF-I had no effect on GRF (10(-9) M)-stimulated GH release at 70 days gestation. It significantly inhibited this effect at 100 days and in prepubertal lamb cells. In 130-day-old fetal and newborn lamb pituitary cultures, IGF-I completely blocked the GH response to GRF.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2896120 TI - Adrenergic inhibition of the stimulatory effect of 3,5,3'-triiodothyronine on calcium accumulation and cytoplasmic free calcium concentration in rat thymocytes. Further evidence in support of the concept that calcium serves as the first messenger for the prompt action of thyroid hormone. AB - Thyroid hormone produces a prompt, plasma membrane-mediated increase in several metabolic functions in the rat thymocyte. These effects of thyroid hormone require calcium and are inhibited by the beta-adrenergic antagonist alprenolol. In the present study, the interrelationship between thyroid hormone and adrenergic agents, and the concept that calcium serves as the first messenger for the rapid action of thyroid hormone in the rat thymocyte are further examined. T3 produced a very rapid and dose-related increase in both 45 calcium accumulation and cytoplasmic free calcium concentration. These effects of T3, like its other calcium-dependent and prompt effects, were inhibited by beta-, but not by alpha-, adrenergic antagonists. Studies with selective beta-adrenergic agents revealed that the inhibitory effect was beta-1 in nature. In addition, beta-adrenergic agonists were found to promote additively T3 action, possibly through their beta 2 activity. Hence, the present study provides further support for the concept that calcium serves as the first messenger in the rapid, plasma membrane-mediated action of thyroid hormone in the rat thymocyte. PMID- 2896121 TI - Mass and in situ activity of tyrosine hydroxylase in the median eminence: effect of hyperprolactinemia. AB - The role of PRL in the control of catecholaminergic hypothalamic neurons of female rats was investigated. The in situ activity of tyrosine hydroxylase (TH) in neurites of these neurons was assayed by measuring the rate of accumulation of L-3,4-dihydroxyphenylalanine (DOPA) in the median eminence (ME) after the administration of a DOPA decarboxylase inhibitor. The mass of TH was measured by an immunoblot assay using rat TH as the standard. Hyperprolactinemia was induced by pituitaries implanted beneath a renal capsule. Hyperprolactinemia resulted in a significant increase in the in situ activity of TH without an increase in TH mass. The release of dopamine from hypothalamic neurons was assessed by measuring the concentration of dopamine in hypophysial portal plasma. The mean concentration of dopamine in portal plasma of rats bearing pituitary implants was 3 times that in controls. When circulating PRL was neutralized by administration of antiserum against rat PRL, the activity of TH was reduced significantly compared to that in animals treated with preimmune serum. In animals bearing pituitary implants, phosphorylation of TH in the ME was not different from that in control animals. We conclude that the biosynthetic and secretory activities of dopaminergic neurons of the hypothalamus are potentiated by PRL, but the potentiation is not due to an increase in the mass of TH or to the capacity of the neurites of the ME to phosphorylate TH. PMID- 2896122 TI - An approach to the determination of the relative potencies of chemical agents during the stages of initiation and promotion in multistage hepatocarcinogenesis in the rat. AB - The potency of carcinogenic agents in eliciting neoplastic lesions has long been a concern of investigators in the field of oncology. This paper describes a method, based on quantitative stereologic calculations, to estimate the relative potency of chemicals as initiating and/or promoting agents. The parameters defined in this paper are: (a) Initiation index = no. foci induced X liver-1 X [mmole/kg body weight]-1; and (b) Promotion index = Vf/Vc X mmol-1 X wk-1. These parameters have been calculated for a number of chemical agents, based both on data from this laboratory and others published in the literature. Neither parameter varied significantly with the dose of two different initiating agents used in this study. The range of promotion indices extended over more than eight orders of magnitude, whereas that of the initiation indices was much less variable. Such parameters may be useful as quantitative estimates of the potency of hepatocarcinogenic agents not only in rodents, but potentially in quantitative risk estimations in the human. PMID- 2896123 TI - Gap genes define the limits of antennapedia and bithorax gene expression during early development in Drosophila. AB - The maintenance of selective patterns of homeotic gene expression within the Drosophila CNS involves cross-regulatory interactions among the genes of the antennapedia and bithorax complexes (ANT-C and BX-C). Such a mechanism does not appear to be responsible for the establishment of these selective expression patterns during early development. Here we show that mutations in several of the gap genes strongly alter the early patterns of Antp and Abd-B expression. The altered patterns that are observed do not always correlate with simple expectations based on cuticular pattern defects observed in advanced-stage mutants. It appears that the initial patterns of Antp and Abd-B expression involve their differential regulation by a common set of gap genes. We propose that the gap genes are largely responsible for integrating the processes of segmentation and homeosis. PMID- 2896124 TI - A gene-specific promoter element is required for optimal expression of the histone H1 gene in S-phase. AB - An H1 gene-specific element (H1-box, 5'-AAACACA-3') modulates S-phase expression of the gene in vivo as judged by analysis of transcripts from histone genes transfected into HeLa cells. Deletion or base-substitution of the element causes a 15- to 30-fold decrease in steady-state H1 mRNA levels in randomly growing cells and eliminates cell cycle control of transcription in synchronized cells. Mutations within the H1-specific element which abolish S-phase control of transcription also eliminate binding of a sequence-specific nuclear factor capable of binding specifically to this region in vitro. Transfection of multiple copies of H1-box elements into cells drastically decreases H1 mRNA levels, mimicking the effect observed when the motif is rendered non-functional by deletion or substitution mutagenesis. In contrast, introduction of mutated H1 elements into cells has no detectable effect. Together, these results imply that an interaction between the H1-box and a sequence-specific trans-acting factor modulates transcriptional control of H1 genes in vivo. PMID- 2896125 TI - Single-dose and multiple-dose pharmacokinetics of etintidine in healthy volunteers. AB - The present study was designed to determine the single- and multiple-dose pharmacokinetic profiles of the H2 receptor antagonist etintidine in healthy volunteers. Etintidine was rapidly absorbed and eliminated after the oral administration of 300 mg base equivalent of etintidine HCl in a capsule formulation to 11 healthy subjects. Comparison of the pharmacokinetics after a single dose and during steady state showed no significant differences (p greater than 0.05) in the mean values of Cmax, tmax, oral clearance, elimination rate constant, and renal clearance, indicating no significant accumulation of etintidine and no apparent time-dependent changes in the pharmacokinetics of etintidine during multiple dose administration. PMID- 2896126 TI - Pharmacokinetics and bioavailability of intravenous and oral chlordesmethyldiazepam in humans. AB - Six healthy, fasting volunteers were given single doses of chlordesmethyldiazepam by 1 mg i.v., or as drops or tablets. Chlordesmethyldiazepam and its metabolite, lorazepam, in multiple plasma samples and in urine collected for 120 h after each dose were determined by electron-capture GLC. Mean kinetic variables for intravenous chlordesmethyldiazepam were: volume of distribution, 1.71 l.kg-1; elimination half-life, 113 h; total clearance, 0.21 ml.min-1.kg-1; cumulative excretion of lorazepam glucuronide 24.2% of the dose. Following a lag time of 15.5 min (tablets) and 4.2 min (drops), which were significantly different, the absorption of oral chlordesmethyldiazepam was a first order process, with apparent absorption half-life values averaging 1.5 h (tablets) and 1.1 h (drops). Bioavailability was 77% for tablets and 79% for drops. PMID- 2896127 TI - Regulation of sterol synthesis by histamine in human mononuclear leukocytes: roles of H1- and H2-receptors. AB - The effect of histamine on sterol synthesis has been investigated in freshly isolated human mononuclear leukocytes from healthy subjects. Incubation of cells for 6 h in a medium containing lipid depleted serum led to a threefold increase in the incorporation of (14C)-acetate or tritiated water into sterols. Histamine 0.3 microM added to the incubation medium at zero time inhibited this induction by 35% with a sigmoidal log dose-effect curve. The receptors mediating this action were characterised pharmacologically by using selective H1- and H2 agonists and -antagonists. The H2-agonists impromidine and 4-methylhistamine mimicked the effect of histamine on sterol synthesis, the suppression being 42% and 31%, respectively, at a concentration of 1 microM. In contrast, the H1 agonist 2-pyridylethylamine did not affect the pathway. The H2-antagonist cimetidine (10 microM) but not the H1-antagonist mepyramine (10 microM) totally reversed the inhibition of sterol synthesis by histamine. The results provide evidence that sterol synthesis in human mononuclear leukocytes is regulated by histamine, which appears to act predominantly via H2-receptors. PMID- 2896128 TI - Efficacy of terfenadine in the treatment of common cold. A double-blind comparison with placebo. AB - We have assessed the effects of terfenadine on rhinitis symptoms associated with the common cold in 91 patients in a double-blind placebo-controlled study. The patients received three doses of either terfenadine 60 mg (n = 44) or placebo (n = 47) at about 12-h intervals, starting in most patients within 48 h from the onset of symptoms. Because of deviations from the protocol, 28 cases were classified as not eligible for efficacy evaluation, but were nevertheless analysed. Excellent/good or moderate efficacy was reported by 63% of eligible and 59% of all patients who received terfenadine (placebo 40% and 51% respectively, p = 0.049 and 0.113 respectively). 68% of eligible and 52% of all patients indicated that they would take terfenadine again (placebo 23%, for both p = 0.002). Two h after tablet intake mean nasal airflow was increased by 11 l.min-1, SD 8 (placebo -1 l.min-1, SD 6, p = 0.005). Symptoms were improved and rhinoscopy showed reduced swelling and redness of the mucosa and reduced nasal secretion and obstruction (basically unchanged in the placebo group). Therefore, terfenadine seems to act favourably on the acute rhinitis symptoms associated with the common cold. Since terfenadine is devoid of anticholinergic activity, nose symptoms during the initial stage of the common cold may be mediated to an important degree by histamine. PMID- 2896129 TI - Effects of age and chronic renal failure on the urinary excretion kinetics of famotidine in man. AB - The plasma and urine concentrations of famotidine, a new, potent H2-receptor antagonist, have been measured in 16 healthy young adults, 8 healthy elderly people and 18 patients with varying degrees of renal dysfunction after intravenous administration. Both the plasma elimination and renal excretion of famotidine were decreased in the elderly volunteers and renal patients. The renal clearance of famotidine averaged 4.43 ml/min/kg (310 ml/min) in normal young volunteers, which exceeded the mean creatinine clearance 1.55 ml/min/kg (109 ml/min), suggesting net secretion is a significant mechanism for elimination of famotidine. The ratio of famotidine renal clearance to creatinine clearance decreased as creatinine clearance decreased; these results suggest that the deterioration in the secretion process was much faster than that in glomerular filtration and are incompatible with the "intact nephron hypothesis". Nevertheless, both total body clearance and renal clearance were significantly correlated with creatinine clearance. The apparent half-life was also significantly correlated with creatinine clearance. Since famotidine is essentially free of dose-related adverse effects, dose adjustment in patients with mild renal insufficiency and in elderly people is not required; however, either a prolonged dosing interval or a decrease in daily dose during long-term therapy may be adapted for the patients with severe renal insufficiency to avoid accumulation and the potential undesirable effects. PMID- 2896130 TI - Multiparameter analysis of transplantable hemopoietic stem cells. II. Stem cells of long-term bone marrow-reconstituted recipients. AB - Marrow obtained from mice (referred to as [X + BM] mice) 3 months after gamma irradiation (9 Gy) and bone marrow inoculation (0.1 femur equivalents) showed a reduced capacity to reconstitute hemopoiesis of irradiated mice and an increased sensitivity to 5-fluorouracil. Sorting of marrow from (X + BM) mice on the basis of low angle and 90 degrees scatter, and low rhodamine 123 fluorescence, showed that the set of cells that in normal mice is enriched for cells efficient at hemopoietic reconstitution manifested the greatest reduction in hemopoietic reconstituting ability. In spite of this reduction this fraction contained as many 13-day spleen colony-forming units (CFU-S13) and high proliferative potential colony-forming cells (HPP-CFC) as the equivalent fraction from normal littermate mice. This could be explained by postulating that neither CFU-S13 nor HPP-CFC are responsible for hemopoietic reconstitution, but that this is dependent on an earlier, pre-CFU-S13 cell. Alternatively only a subset of either CFU-S13 or HPP-CFC is responsible for long-term hemopoietic reconstitution after lethal irradiation. It would appear that at present there is no adequate method of predicting the hemopoietic reconstituting ability of a given marrow, other than to test it by injection into lethally irradiated hosts. PMID- 2896131 TI - [Search for and study of biologically active substances with psychotropic activity among the N-nicotinoyl derivatives of glutamic and gamma-aminobutyric acids]. AB - Four new derivatives of glutamic and gamma-aminobutyric acids influencing the central nervous system were produced. By the character of their action they refer to the substances of the sedating tranquilizing type without the myorelaxant component. The drug activity degree depends on its ability to penetrate through cell membranes that is in turn determined by the structure of the compound. PMID- 2896132 TI - [Dependence of the absorption through the human oral mucosa of antihistaminic (H1) preparations on their physicochemical properties]. AB - Antihistaminic (H1) drugs pipolphen, suprastin and dimedrol are characterized according to absorption through human oral mucosa and distribution between phosphate buffer solution and organic solvents at various medium pH values. Their constants of ionization and coefficients of distribution in the n-octanol- phosphate buffer system, pH 7.4, as well as the bound fraction at the interaction of these drugs with human serum albumin were determined. The relationship between absorption through human oral mucosa of antihistaminic drugs and the hydrophobic character of their molecules and constants of ionization was found. An attempt was made to predict for them on the basis of the authors' own results and literature data possible pharmacokinetic and pharmacodynamic behavior in the organism. PMID- 2896133 TI - A zebrafish engrailed-like homeobox sequence expressed during embryogenesis. AB - The zebrafish genome was found to contain two sequences which cross-hybridize strongly with the engrailed gene of Drosophila. Several independent clones containing one of these cross-hybridizing sequences were isolated from a zebrafish genomic library. Characterization of this region (ZF-EN) by DNA sequencing showed that it shares about 70% sequence identity with the engrailed homeobox. More extensive homeobox homology (greater than 90%) was found relative to the murine En genes. The closest relationship exists between ZF-EN and En-2 where the C-terminal domains (104 amino acids) encoded by these genes are almost identical. We also observed that ZF-EN and En-2 are very similar with respect to their transcript sizes and temporal expression patterns. PMID- 2896134 TI - Beta-endorphin and islet hormone release in type-2 diabetes mellitus the effects of normoglycemia, enkephalin, naloxone and somatostatin. AB - The present study was aimed at characterizing the effects of beta-endorphin on plasma glucose, insulin and glucagon plasma levels in subjects with type-2 diabetes mellitus. Infusion of 0.5 mg/h human beta-endorphin produced significant and simultaneous increments in both insulin and glucagon concentrations and decreased plasma glucose levels (-18 +/- 4 mg/dl, 60 min level, p less than 0.01). When the same diabetics were rendered euglycemic by an insulin infusion (1 mU/kg/min), beta-endorphin did not produce the expected decrease in plasma glucose concentrations nor raise plasma insulin levels; only the response of glucagon was preserved. Normal subjects were rendered hyperglycemic by an intravenous glucose infusion to match the plasma glucose levels of diabetic subjects. In this condition, beta-endorphin produced a significant increase of insulin concentrations, whereas glucagon remained suppressed. The intravenous administration of the long-acting met-enkephalin analogue DAMME (0.25 mg) blunted the hormonal responses to the subsequent beta-endorphin infusion in diabetic patients, although the inhibition was short-lived (30-40 min). Naloxone (5 mg), an opiate antagonist, did not produce any significant change in the insulin and glucagon responses to beta-endorphin, while somatostatin (0.25 mg/h) completely abolished the hormonal responses to the opioid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896135 TI - Expression of the Sex combs reduced protein in Drosophila larvae. AB - We have generated a monoclonal antibody that binds specifically to the protein product of the homeotic Sex combs reduced (Scr) gene of Drosophila, and have mapped the patterns of Scr expression in late third instar larvae. Virtually the entire prothoracic leg imaginal disc expresses the gene, although the levels of expression vary in different disc regions. This heterogeneity does not reflect the compartmental domains defined by engrailed gene expression. Expression is also observed in the cells of the humeral and labial discs, and there is a small patch of Scr-expressing cells in the antenna disc. The gene is expressed in adepithelial cells of the three thoracic leg discs, but not in the wing or haltere discs. In the central nervous system, Scr expression is confined to a narrow band of cells in the subesophageal region of the ventral ganglion. The results are discussed with respect to the known genetic requirements for Scr+ function. PMID- 2896136 TI - [Gamma-glutamyltransferase]. PMID- 2896137 TI - Role of epidermal growth factor in healing of chronic gastroduodenal ulcers in rats. AB - The healing of acetic acid-induced gastric and duodenal ulcers was examined together with biochemical indices of growth in gastric and duodenal mucosa in rats with intact or removed salivary glands after treatment with epidermal growth factor (EGF) or somatostatin, or both. After the extirpation of salivary glands, the healing rate of gastric and duodenal ulcerations was delayed and gastric content of immunoreactive EGF was reduced. This was accompanied by a significant decrease in the contents of deoxyribonucleic acid and ribonucleic acid in the gastric and duodenal mucosa. Repeated administration of EGF either subcutaneously or orally accelerated the healing of gastroduodenal ulcers in rats with intact salivary glands and completely reversed the delay in ulcer healing in sialoadenectomized animals. These effects were also accompanied by a significant increase in the growth parameters of gastric and duodenal mucosa. Administration of somatostatin, which prevented the growth-promoting action of subcutaneous EGF, resulted in a significant decrease in the EGF-stimulated healing of gastric and duodenal ulcerations in both intact and sialoadenectomized rats. Our findings suggest that cell proliferation is an important factor in healing of gastric and duodenal ulcerations and that EGF plays an important role in ulcer healing due to its mitogenic action. PMID- 2896138 TI - In vitro effects of the long-acting somatostatin analogue SMS 201-995 on electrolyte transport by the rabbit ileum. AB - We have investigated the in vitro properties of SMS 201-995, a long-acting somatostatin analogue, on electrolyte transport in rabbit ileum. Similar to native somatostatin, serosal addition of this compound inhibits electrogenic anion secretion and stimulates neutral sodium and chloride absorption. Both compounds have similar maximal effects on ion transport; however, the ED50 of SMS 201-995 (2.4 X 10(-10) M) was 60 times less than that for somatostatin. In addition, unlike somatostatin, no inherent tachyphylaxis was observed in response to SMS 201-995. The antisecretory profile of SMS 201-995 was also compared with that of epinephrine. Unlike treatment with epinephrine, pretreatment of tissues with SMS 201-995 did not directly inhibit electrogenic anion secretion stimulated by vasoactive intestinal polypeptide, calcium ionophore A23187, and bethanechol. In contrast, this agent blocked vasoactive intestinal polypeptide and bethanechol inhibition of net sodium absorption. We conclude that SMS 201-995 has several unique in vitro properties that may explain its greater biologic activity compared with that of somatostatin. Its effects on secretagogue-stimulated electrogenic anion secretion and electroneutral NaCl absorption appear to differ. PMID- 2896139 TI - Comparison of delayed-release 5-aminosalicylic acid (mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis. AB - To assess the safety and efficacy of delayed-release mesalazine (5-aminosalicylic acid) as maintenance treatment for patients with ulcerative colitis, 100 patients with quiescent colitis were randomly grouped to receive either delayed-release mesalazine or an equivalent dose of enteric-coated sulfasalazine in a 48-wk trial. Groups were comparable for age, sex, and duration and extent of disease. Relapse rates at 48 wk were as follows: sulfasalazine 38.6% (95% confidence limits, 24%-54%) and mesalazine 37.5% (95% confidence limits, 24%-53%), chi 2 = 0.01, p greater than 0.90. Mean time to relapse, cumulative relapse rate, and relapse severity were similar in the two groups. Headaches and upper gastrointestinal symptoms--common at trial entry--improved to a greater extent in patients receiving mesalazine. Delayed-release mesalazine is an effective treatment for maintaining ulcerative colitis remission and is associated with fewer side effects than equivalent doses of enteric-coated sulfasalazine. PMID- 2896140 TI - Investigations of endocrine cells in the gastrointestinal tract and pancreas during the metamorphosis of an anuran (Alytes obstetricans L.): histochemical detection of APUD cells. AB - Endocrine cells were detected at premetamorphosis, prometamorphosis, climax, and juvenile stages using an amine-inducing fluorescence technique with or without previous L-3,4-dihydroxyphenylalanine (L-DOPA) treatment. At premetamorphosis, serotonin cells exhibited yellow fluorescence in the gut primary epithelium of the L-DOPA untreated animals. In the treated animals, green fluorescent APUD cells could be seen in addition to the serotonin cells. In the pancreas, numerous clusters of fluorescent APUD cells were observed. At prometamorphosis the number of fluorescent cells increased in the intestinal primary epithelium and, close to the basal membrane, numerous small regenerative buds devoid of fluorescent cells appeared. In the pancreas of L-DOPA-treated animals, two types of APUD cells could be distinguished by their different fluorescence intensities. At the climax stage, the stomach developed and APUD cells were detectable in the gastric glandular buds. The degenerated primary intestinal epithelium was progressively removed in the intestinal lumen. At this stage, the regenerative buds of the secondary epithelium exhibited APUD cells. In the disorganized pancreas, the induced fluorescence decreased strongly. At the juvenile stage, cords of APUD cells displayed a cytoplasmic green fluorescence in the pancreas. In the stomach and intestine, serotonin and APUD cells were numerous. PMID- 2896142 TI - [Definition, significance and measurement of disease concepts of patients. The Disease Concept Scale for schizophrenic patients]. AB - Illness concepts represent cognitive interpretations, explanations and predictions of health status. Illness concepts are a consequence and an expression of the patient's cultural background, view of the world, value system, way of living, and personal life experiences. Illness concepts are significant in that they influence patient's informed consent and compliance behavior. Illness concepts have been formulated in phenomenological-descriptive, formal-structural and psychological approaches. Based on these alternative conceptualizations, a scale was developed to measure seven dimensions of illness concepts. including trust in medication, trust in the treating physician, negative treatment expectations, guilt, chance control, susceptibility, and idiosyncratic assumptions. The reliability and validity of the scale (KK-scale) was tested in a group of schizophrenic patients in different treatment settings. The psychometric properties of the scale were found to be satisfactory. Support for the discriminant validity of the scale was found in relation to patient's age, education, sex, and compliance treatment institution. PMID- 2896143 TI - [Significance of neurotransmitters and neuromodulators in regulating respiration. A. Central aminergic neurons]. AB - Experimental and clinical findings on the role of the central aminergic mechanisms in the control of respiration are reviewed. Dopamine, histamine, norepinephrine and serotonin inhibit spinal cord and cortical neurons; acetylcholine stimulates these neurons. The importance of these pharmacological effects for the control of respiration is not yet clear. Brain stem dopaminergic and serotonergic mechanisms stimulate respiratory neurons; a brain stem noradrenergic mechanism inhibits these neurons. A cholinergic mechanism is involved in the control of central chemosensitivity, and probably of the respiratory periodicity. Histamine stimulates the brain stem neurons, its effects on respiratory neurons have not yet been investigated. PMID- 2896141 TI - The Hox-2 homeo box gene complex on mouse chromosome 11 is closely linked to Re. AB - Restriction fragment length polymorphisms have been identified between inbred strains of mice for the homeo box gene complex Hox-2. These genetic markers were used to follow the segregation of different Hox-2 alleles among recombinant inbred strains of mice and among the progeny of a three point genetic cross. The results place the Hoax-2 locus approximately 1 cM from the rex (Re) locus on mouse chromosome 11. PMID- 2896144 TI - [Differential diagnosis of malignant hyperthermia, febrile catatonia and neuroleptic malignant syndrome. A case comparison]. AB - Malignant Hyperthermia (MH), Lethal Catatonia (LC), and Neuroleptic Malignant Syndrome (NMS) are known as rare potential lethal diseases. MH and NMS--both being drug-induced--have in common some main symptoms. LC and NMS, on the other hand, are hardly distinguishable by clinical means. After presentation of the case reports the differential diagnosis of the syndromes is discussed. While there is strong evidence for the MH to be drug-induced, the NMS cannot be explained sufficiently in this way. Clinically both can be differentiated. Lethal catatonia is a syndrome rather than a specific disease. Differential diagnosis for NMS is possible by the neuroleptic withdraw-trial. PMID- 2896145 TI - Spleen size in adult T-cell leukemia virus (ATLV) carriers. PMID- 2896147 TI - Physician assistants as alternatives to foreign medical graduates. PMID- 2896146 TI - An investigation into the possible development of chronic tolerance to analgesia and dependence on prolactin. AB - The possibility of the presence of chronic tolerance to the analgesic effect of prolactin and of dependence was tested. Repeated administration of prolactin resulted in the loss of analgesic activity, indicating the development of chronic tolerance. Neither a high dose of, or chronic treatment with prolactin followed by naloxone elicited any characteristic withdrawal signs, suggesting the absence of dependence. Similarly, abrupt withdrawal of prolonged prolactin treatment also did not elicit withdrawal signs. However, in the same model, the morphine naloxone combination and spontaneous withdrawal of chronic morphine treatment produced characteristic withdrawal signs, namely jumping, wet shakes, and body tremor. The data support the view that tolerance and dependence can be dissociated from each other and that different mechanisms may operate in these phenomena. The absence of liability to dependence with prolactin strengthens the contention that prolactin may be a potential drug for combatting opiate dependence. PMID- 2896148 TI - H2-antagonists and motility of the upper gastrointestinal tract in man. PMID- 2896149 TI - Effect of somatostatin on skin lesions and concentrations of plasma amino acids in a patient with glucagonoma-syndrome. AB - A case of glucagonoma syndrome in a 58-year-old male patient who had the typical skin lesions associated with severe hypoaminoacidemia is described. The decrease in amino acids has been proposed to be causally related to the dermatosis. Furthermore, it has been shown previously that somatostatin rapidly improves skin lesions in glucagonoma patients. Therefore, plasma amino acid levels were determined before and during an infusion of somatostatin prior to surgical removal of the tumor in the tail of the pancreas. During somatostatin infusion in combination with total parenteral nutrition, 10 out of 22 amino acids were in the normal range. Thus it seems unlikely that normalization of amino acid levels is responsible for the rapid improvement in skin lesions in glucagonoma patients. On the other hand it cannot be excluded that partial normalization of amino acids contributed to the observed healing process. Nevertheless, somatostatin administered prior to surgery is a useful therapeutic regimen in these patients. PMID- 2896150 TI - Effects of SGB-1534, a new synthesized phenylpiperazine derivative, on blood pressure and heart rate in stroke-prone spontaneously hypertensive rats. AB - The present study was undertaken to elucidate the effects of a new synthesized phenylpiperazine derivative SGB-1534 on mean arterial blood pressure and heart rate in stroke-prone spontaneously hypertensive rats(SHRSP). SGB-1534 (0.05 and 0.5 mg/kg, i.v.) produced a significantly greater decrease in mean arterial blood pressure in SHRSP than in normotensive Wistar Kyoto rats(WKY). Heart rate also tended to decrease in parallel with the decrease in mean arterial blood pressure in SHRSP. In this study, it was revealed that SGB-1534 has an antihypertensive effect in SHRSP. An attempt was made to elucidate the hypotensive mechanism of SGB-1534 using WKY. SGB-1534 (0.5 mg/kg, i.v.) significantly inhibited pressor responses to norepinephrine (5 micrograms/kg, i.v.) and methoxamine (50 micrograms/kg, i.v.). SGB-1534 (0.5 mg/kg, i.v.) did not affect the preganglionic sympathetic adrenal nerve activity. The present findings suggest that the action site of SGB-1534 is not in the central nervous system, but in the peripheral alpha 1-adrenoceptors in rats. PMID- 2896151 TI - [Measurement of human serum and liver tissue immunoreactive gamma-glutamyl transpeptidase in patients with various liver diseases]. AB - A solid phase enzyme-linked immunosorbent assay for human immunoreactive gamma glutamyltranspeptidase(gamma-GTP) was developed. The working range by this assay was from 1 ng to 100 ng. Serum immunoreactive gamma-GTP was significantly elevated in patient with hepatocellular carcinoma and moderate elevation was found in liver cirrhosis. On the other hand, in sera of patients with non neoplastic disease, including acute hepatitis, chronic hepatitis, fatty liver, hemangioma, the immunoreactive gamma-GTP was not significantly elevated. No correlation was found between the serum levels of gamma-GTP determined by enzymatic assay and enzyme-linked immunosorbent assay. In the tissues of hepatocellular carcinoma and metastatic liver tumor, the immunoreactive gamma-GTP contents were also elevated, which were well correlated with the enzyme contents in sera. When immunohistochemical study was carried out, the immunoreactive gamma GTP was detected diffusely not only in the cell membrane and bile canaliculi but also in the cytoplasm of cancer cell. These results suggest that the hepatoma tissues contain an immunologically active, but enzymatically inactive form of gamma-GTP enzyme. PMID- 2896153 TI - Evolutionary conservation of the human homologue of the yeast cell cycle control gene cdc2 and assignment of Cd2 to chromosome 10. AB - The human homologue of the fission yeast Schizosaccharomyces pombe cell cycle control gene cdc2 has been assigned to chromosome 10. DNA hybridization reveals that this gene is highly conserved in vertebrates. The human CDC2 gene probe detects a simple two-allele polymorphism in Taq1-digested DNA. PMID- 2896154 TI - Linkage heterogeneity and fragile X. AB - A multipoint test of heterogeneity on published data from 57 families with the fragile X syndrome has been undertaken. The hypothesis being tested was that there are two loci coding for fragile X expression, mutations at either of which can produce the phenotype. No predivision of the families was undertaken, as the test used an admixture parameter. Maximum likelihoods of the hypothesis have been calculated and compared with those produced on assuming a single locus for fragile X. The data do not suggest that there are two such loci within the interval between probes 52a and St14. In particular, the large kindred published by Camerino et al. (1983) does not supply convincing evidence of heterogeneity under this test. It is argued that the observed heterogeneity between factor IX and fragile X must have another explanation. There is some evidence for a second locus for fragile X outside the interval noted above; this locus being most probably proximal to these probes. The majority of the data suggesting this result comes from a family published by Davies et al. (1985). PMID- 2896155 TI - Linkage disequilibrium between RFLP haplotype 2 and the affected PAH allele in PKU families from the Berlin area of the German Democratic Republic. AB - Probands from 26 PKU-affected families of the Berlin area were analyzed with respect to the allele frequency distribution of six RFLPs in linkage with the normal and the PKU alleles of the phenylalanine hydroxylase gene. These investigations confirm most of the RFLP haplotypes observed by Guttler and colleagues in the Danish population and describe two additional ones. They detect no significant differences in the single RFLP or RFLP haplotype distribution on the normal chromosomes in comparison with the Danish families and confirm a prevalent association of the RFLP haplotypes 1, 4, and 7 with the normal PAH allele. In contrast to the Danish investigations, in our study the PKU allele is found most frequently linked to haplotype 2, rather then to haplotype 3. In one of our patients we found a substitution of the normal 19-kb MspI fragment by a 13.5- and a 5.5-kb fragment, reported up to now only in one other German family. PMID- 2896152 TI - DNA polymorphism and the study of disease associations. AB - Recombinant DNA approaches to disease analysis may be as applicable to studies of disease association as they are to the analysis and diagnosis of single-gene defects. Population and/or family association analyses, using restriction fragment length polymorphisms around candidate genes as markers, have been employed to study conditions such as atherosclerosis and disease with an HLA association. Progress made to date in disease-association studies using recombinant DNA methodology is reviewed, the rationale behind such studies is examined and associated problems and pitfalls discussed. PMID- 2896156 TI - Linkage disequilibrium between mutation and RFLP haplotype at the phenylalanine hydroxylase locus in the German population. AB - Restriction fragment length polymorphism (RFLP) haplotypes at the phenylalanine hydroxylase (PAH) locus have been determined in 60 German families with PAH deficiency. Similar to the Danish population, about 90% of the mutant alleles are confined to four distinct haplotypes. There are however, differences in the frequency distribution of these haplotypes among the mutant alleles between the two populations. Using an oligonucleotide probe for the splicing mutation associated with mutant haplotype 3 in the Danish population, a tight association between the mutation and the RFLP haplotype has also been observed in Germany. The results provide strong evidence that the splicing mutation occurred on a haplotype 3 chromosome and that the mutant allele has spread into different populations among Caucasians. PMID- 2896157 TI - Phenylketonuria: distribution of DNA diagnostic patterns in German families. AB - The distribution of DNA haplotype constellations within the phenylalanine hydroxylase (PAH) gene was investigated in 44 German families affected with phenylketonuria (PKU). The haplotype frequencies differed significantly from those observed in a Danish population. Furthermore, ten haplotypes were identified in addition to the 12 previously described. In one of ten PKU alleles linked to haplotype 3, the G to A transition at the 5' splice donor site of intron 12 could not be confirmed with the use of synthetic DNA probes. According to these data, which are still limited, carrier testing and prenatal diagnosis should be possible in 70% of individuals at risk in the German population. PMID- 2896158 TI - X-linked cleft palate: the gene is localized between polymorphic DNA markers DXYS12 and DXS17. AB - The gene involved in an X-linked form of cleft palate has been finely mapped using 14 restriction fragment length polymorphic (RFLP) markers that cover the long arm of the X chromosome. By the combination of deletion mapping and linkage analysis, the gene has been localized between the anonymous DNA markers DXYS12 on the proximal side, and DXS17 distally. PMID- 2896159 TI - A HindIII RFLP and a gene lesion in the coagulation factor VIII gene. AB - The presence and inheritance of restriction fragment length polymorphisms (RFLPs) and gene lesions in the coagulation factor VIII gene were investigated in 15 hemophilia families. An abnormal HindIII 2.6-kb band, previously detected in a severe hemophiliac, was observed in a not severely affected patient and also in the normal gene of a woman carrying a hemophilic gene in which the lesions was found. The TaqI site in exon 24 of this defective gene was removed by a C to T transition causing an amino acid change (Arg----Gln). Very low amounts of factor VIII activity and antigen were detected in the severely affected grandson. The presence of the HindIII 2.6-kb fragment in both normal and pathological genes indicates that a factor VIII RFLP without functional meaning was found. Its frequency, determined in 60 chromosomes, is 0.18. Double digestions enabled us to map the polymorphic site 3' to the exon 19. PMID- 2896160 TI - DNA polymorphism unique for a complotype with deletion of HLA-linked C4B and 21 hydroxylase B genes causing congenital adrenal hyperplasia. AB - Defects in the enzyme steroid 21-hydroxylase (21-OH) result in congenital adrenal hyperplasia (CAH), a frequent disorder of steroid biosynthesis. The gene encoding the enzyme, 21-OHB, has been mapped adjacent to the complement component C4B gene in the human HLA gene complex. DNA-level analyses of patients with CAH have shown that the 21-OHB gene has often been deleted, but the detection of 21-OHB deletions in heterozygotes is often problematic because it is based on relative band intensities. We here report a DNA polymorphism in the C4A91 gene unique to one particular type of 21-OHB deletion occurring solely with a complement phenotype BfF C4A91 B null, shown earlier to be frequent in CAH patients. This marker makes direct detection of the 21-OHB deletion in heterozygotes possible. PMID- 2896161 TI - Non-specific aorto-arteritis. PMID- 2896162 TI - Profile of renal artery stenosis with a reference to aortoarteritis. PMID- 2896163 TI - Effect of controlled release formulation of Bacillus sphaericus on Mansonia breeding. PMID- 2896164 TI - Evaluation of two new juvenile hormone compounds against mosquito vectors. PMID- 2896165 TI - Laboratory & field evaluation of three insect growth regulators against mosquito vectors. PMID- 2896166 TI - Amoebic hepatitis as a precursor of suppurative amoebic liver abscess. PMID- 2896167 TI - The march of haemapheresis--cell separators. PMID- 2896168 TI - A review of Asherman's syndrome, and results of modern treatment. PMID- 2896169 TI - Sexual behavior of infertile couples. AB - The role of sexual dysfunction was evaluated among 98 couples during infertility examination. The wife and the husband were interviewed separately and together. Sixty-six women were willing to report daily their sexual behavior in association with recording basal body temperature. Male sexual dysfunction was the primary cause of infertility in five couples (5%). Three pregnancies resulted after examination and simultaneous supportive discussion. Following a simple diary on sexual behavior, 19 of 66 women conceived (29%). Fourteen of these 19 women reported orgasm within two days preceding elevated basal body temperature. Open discussion about sex was possibly therapeutic. Infertility examinations should include an evaluation of the sexual behavior of couples, with special reference to frequency and timing of coitus. PMID- 2896170 TI - Twin gestation induced with hMG-hCG in a patient with a bicornuate uterus: report of a successful delivery. PMID- 2896171 TI - Changes in cervical mucus after diathermocoagulation of the cervix. AB - We have studied the principal chemophysical properties of cervical mucus obtained before and after diathermocoagulation (DTC) in 35 patients participating in a program for prevention of cervical carcinoma. Two months after DTC there were significant decreases in the cervical scores for both exo- and endo-cervical mucus (Moghissi scale). Twelve patients with favorable pre-DTC scores, whose condition had deteriorated 2 months subsequent to treatment, again displayed normal scores in both sites 1 year after DTC. We feel, therefore, that DTC does not cause any permanent change in the chemophysical properties of the cervical mucus, but instead only temporary deterioration during the repair phase. PMID- 2896172 TI - Serum levels of gonadotropins, prolactin, and testosterone in oligo/azoospermic Nigerian males. AB - To determine the frequency of hormonal abnormalities in a Nigerian population of male partners of infertile relationships, serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin, and testosterone were estimated using radioimmunoassay techniques in 454 oligo/azoospermic male partners of infertile marriages. Of these men, 272 (59.9%) had an abnormal serum level of one or more of the hormones. Hyperprolactinemia, found in 144 patients, was the most common hormonal disorder in the group. Elevated serum gonadotropins associated with low serum testosterone were found in 120 (26.4%) patients, while 32 (7%) had a reduced serum testosterone concentration in association with low serum gonadotropins. Since hyperprolactinemic, hypogonadotropic, and normogonadotropic testicular failures are amenable to treatment, routine hormonal evaluation of male partners of infertile marriages is suggested in Nigeria and other places where this practice is uncommon at present. PMID- 2896173 TI - Acid phosphatase activity in human semen. AB - Acid phosphatase (ACP) was studied in normal and abnormal human semen of individuals not suffering from testosterone deficiency. Study of ACP activity was performed on 365 men referred to the OPD clinic of L.T.M.G. Hospital, Bombay. Semen samples were classified into five groups according to sperm concentration, vitality, motility, and morphology. An inverse correlation was found between enzyme activity and sperm concentration. Statistical analysis revealed that ACP activity was maximal in the azoospermic group, and decreases as the sperm concentration increases. On the basis of this, measurement of ACP in human semen may be useful in clinical practice. PMID- 2896174 TI - Prostaglandin F2 alpha and E2 release by peritoneum with and without endometriosis. AB - Peritoneal endometriotic implants and adjacent normal peritoneum from five patients were analyzed for prostaglandin (PG) release. Each tissue biopsy was incubated using medium 199 in triplicate at 37 degrees C for six hours, and PGF2 alpha and PGE2 concentrations were measured in the incubation medium every two hours. This study demonstrates that peritoneum involved with endometriosis releases significantly more PGF2 alpha and PGE2 (P less than .05) than adjacent normal peritoneum, and suggests that peritoneal endometriotic implants may be a source of the elevated peritoneal fluid PG levels previously reported in patients with endometriosis. PMID- 2896175 TI - Control of follicular maturation in the mouse by a nonsteroidal regulator from sheep follicular fluid. AB - Follicular fluid from sheep ovaries was gel-chromatographed on Sephadex G-100, and the retarded active fraction (Fr-IV, Kav = 1) was rechromatographed on G-25 (GF2). When injected into pseudopregnant mice, it did not affect corpus luteum function, but at the time of the termination of pseudopregnancy ovulation was suppressed. A dose of 20 micrograms GF2 when injected into cycling mice inhibited follicular maturation and ovulation. Plasma progesterone levels were also reduced, indicating the role of a nonsteroidal factor in follicular maturation, ovulation, and luteinization. PMID- 2896176 TI - Interference in follicular maturation following acute intranasal LH-RH agonist administration during mid and late follicular phase. AB - A dose of 300 micrograms of Buserelin was insufflated into the nose twice on a single day between days 5 and 14 in 23 regularly ovulating volunteers, for a total of 25 cycles. The acute gonadotropin response to the first dosing at 8 A.M. was maximal on treatment days 9 to 14 and was followed by a 2- to 10-fold increase in serum estradiol at 10 A.M. and 2 P.M. The response to the second dosing 10 hours later (6 P.M.) was preserved on treatment days 5 to 8, but was diminished on treatment days 9 to 14. Daily endocrine determinations of serum LH, FSH, estradiol, and progesterone revealed three different situations, according to the time of treatment: In 6 cycles (24%), LH-RH agonist treatment on days 5 to 8 was associated with a delayed LH surge, followed by a normal or short luteal phase; when Buserelin was administered between days 7 and 11 in 16 cycles (64%), there was not subsequent LH surge--progesterone remained in the follicular phase range in 9 cycles, and inadequate secretion of serum progesterone was found along with a luteinized follicle in 5 cycles, being in the luteal phase range in only 2 cycles; in three cycles (12%), the treatment coincided with a presumptive LH surge, and the luteal phase was deficient in two cases. There were no clinical side effects of treatment. Immediate posttreatment cycles were normal. Acute intranasal LH-RH agonist administration predominantly delayed ovulation when administered at midfollicular phase, and interfered with final follicular maturation when given in the late follicular phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896177 TI - Sialic acid content of human spermatozoa in relation to age and quality of sperm. AB - Sialic acid (SA) has been estimated in human spermatozoa separated according to age by the use of a discontinuous gradient of human serum albumin (HSA), and according to quality (viability and motility) by the use of a discontinuous gradient of bovine serum albumin (BSA). The amount of SA in the "mature" sperm was 3.5 +/- 0.7 (SD) micrograms/mg protein, whereas in the immature sperm subpopulation, enriched with morphologically abnormal sperm, it was 6.9 +/- 3.4 micrograms/mg protein (P = .05). SA estimated in spermatozoa separated according to quality had values of 3.6 +/- 1.2 micrograms/mg protein in sperm of higher quality and 4.1 +/- 1.3 micrograms/mg protein in that of lower quality; this difference was not of statistical significance. It is suggested that changes in SA levels might reflect differences in the degree of sialylation of protein in the subpopulation of sperm, and thus be related to various stages in the fertilization process. PMID- 2896178 TI - Effects of somatostatin on the insulin- and gastric inhibitory polypeptide stimulated fatty acid esterification in rat adipose tissue. AB - Relations exist between insulin, somatostatin (S) and gastric inhibitory polypeptide (GIP) for the reciprocal control of their secretion but also for their role in lipid metabolism. In the present experiment, we studied the effects of somatostatin on fatty acid incorporation into epididymal adipose tissue (FIAT) of Wistar rats when it was stimulated by insulin and GIP. Cyclic somatostatin-14 was used at physiological (S1 : 50 pg/ml, S2 : 200 pg/ml) and supraphysiological (S3 : 666 pg/ml) concentrations whereas insulin and GIP were used at postprandial levels (100 microU/ml and 2 ng/ml respectively). Results were expressed as percent of basal incorporation (without any hormones). Somatostatin inhibited basal FIAT at all concentrations and totally abolished the insulin-stimulated FIAT (from 106.4 +/- 2.3 per cent with insulin alone to 92.6 +/- 2.5 per cent with S3, P less than 0.001). GIP enhanced the insulin-stimulated FIAT from 106.4 +/- 2.3 per cent to 113 +/- 3.0 per cent (P less than 0.01). On the contrary, when somatostatin was added with GIP and insulin, FIAT decreased to 102.3 +/- 2.5 per cent for S1 (P less than 0.01) and to 98.2 +/- 2.6 per cent for S3 (P less than 0.001). These results indicate that somatostatin totally inhibits the fatty acid esterification induced by insulin and in the same proportions that induced by insulin associated with GIP. Somatostatin is not only an inhibitor of the secretion of these hormones but also a regulator of their biological action in adipose tissue. PMID- 2896179 TI - Effects of LY104119, a thermogenic weight-reducing compound, on norepinephrine concentrations and turnover in obese and lean mice. AB - Dopamine (DA) accumulation in interscapular brown adipose tissue (IBAT), heart, and liver was linear for more than 60 min after injection of 1-cyclohexyl-2 mercapto-imidazole (CHMI), a DA beta-hydroxylase inhibitor, into mice and served as an index of the rate of synthesis of norepinephrine (NE) in these tissues. There was a marked diurnal rhythm of DA accumulation in all three tissues of mice fed ad libitum, the rhythm being dampened in obese mice in IBAT and liver but not in heart. LY104119 acutely decreased NE concentration in IBAT, heart and liver, but not in brain, and it also decreased DA accumulation after CHMI in IBAT, heart and liver. Chronic administration of LY104119 at doses that stimulated thermogenesis and reduced body weight decreased NE turnover in heart and liver but increased NE turnover in IBAT. These data suggest that the increased thermogenesis in IBAT after chronic LY104119 treatment may be mediated by increased noradrenergic tone. PMID- 2896180 TI - Muscles of diabetic (db/db) mice: fibre size, fibre type and the effects of a thermogenic, beta-adrenoceptor agonist. AB - The size and morphological characteristics of muscles from diabetic obese (db/db) mice and their normal lean littermates were investigated. The soleus muscles were similar in size in diabetic and normal mice but the biceps brachii and gastrocnemius were significantly lighter in the diabetic animals. In the biceps brachii the small size resulted from an overall reduction in fibre diameter, which was most acute in the fast white fibres, and an increase in the proportion of smaller fast intermediate fibres. Treatment of diabetic mice with BRL 26830 a thermogenic, beta-adrenoceptor agonist, restored the weight, fibre diameter and fibre type composition of the biceps brachii to that of lean littermates. This treatment also increased the weight of the gastrocnemius, together with its protein content. Since BRL 26830 restored normoglycaemia in the diabetic mice, without decreasing their body weight, we suppose that it improved insulin action in their muscles and this, in turn, stimulated muscle growth. PMID- 2896181 TI - A comparison of effects of sulfasalazine and its metabolites on the metabolism of endogenous vs. exogenous arachidonic acid. AB - Sulfasalazine and, to a lesser extent, 5-aminosalicylic acid and N-acetyl aminosalicylic acid, were found to block production of 5-hydroxy-6,8,11,14 eicosatetraenoic acid, leukotriene B4 (LTB4), and LTB4 stereoisomers from both exogenous and endogenous [14C]arachidonic acid (14C-AA) in ionophore A23187 (1 microgram/ml)-stimulated human neutrophils. Lipids were assessed by thin-layer chromatography and reverse-phase high-pressure lipid chromatography. Sulfasalazine blocked the synthesis of these metabolites from both exogenous and endogenous AA, but was more effective in blocking the metabolism of exogenous than endogenous AA. The IC50 for sulfasalazine in blocking the synthesis of LTB4 was 0.8 mM when exogenous AA was the substrate and 2.8 mM when endogenous AA was the substrate. N-Acetyl-aminosalicylic acid showed a similar pattern, but was less effective than sulfasalazine (IC50 for exogenous AA was 5.4 mM, and for endogenous AA was 8.0 mM). 5-Aminosalicylic acid had similar effects with an IC50 of 6.0 and 6.4 mM respectively. Sulfasalazine but not 5-aminosalicylic acid inhibited the incorporation of arachidonic acid into phospholipids and triglycerides. Sulfasalazine, but not its metabolites, inhibited the release of 14C-AA from membrane phospholipids in a dose-dependent manner (46.0% inhibition with 4 mM sulfasalazine). Sulfasalazine also blocked the metabolism of exogenously added LTB4 to 20-OH LTB4 and 20-COOH LTB4 with an IC50 of 2 mM. Our findings suggest that under physiologic conditions, with endogenous AA as a substrate, sulfasalazine acts as an inhibitor of lipoxygenase, of phospholipase A2 and of LTB4 metabolism, whereas 5-aminosalicylic acid and N-acetyl aminosalicylic acid inhibit only lipoxygenase. PMID- 2896182 TI - Will you and your contract meet in court? PMID- 2896183 TI - The ISMS Contract Review Service. Guiding physicians through the maze of options. PMID- 2896184 TI - Physician responsibility in hospital patient discharge. PMID- 2896185 TI - Splenic abscess. PMID- 2896186 TI - Hemorrhagic metastatic melanoma. PMID- 2896187 TI - Anuria caused by renal artery stenosis. PMID- 2896188 TI - Arg-220 of the PstA protein is required for phosphate transport through the phosphate-specific transport system in Escherichia coli but not for alkaline phosphatase repression. AB - The pstA gene encodes an integral membrane protein of the phosphate-specific transport system of Escherichia coli. The nucleotide change in the previously described pstA2 allele was found to be a G----A substitution at position 276 of the nucleotide sequence, resulting in the premature termination of translation. Three mutations in the pstA gene were produced by site-directed mutagenesis. The amino acid substitutions resulting from the three site-directed mutations were Arg-170----Gln, Glu-173----Gln, and Arg-220----Gln. These amino acid residues were selected because a previous PstA protein structure prediction placed them within the membrane. The Arg-220----Gln mutation resulted in the loss of phosphate transport through the phosphate-specific transport system, but the alkaline phosphatase activity remained repressed. Neither the Arg-170----Gln nor the Glu-173----Gln mutation affected phosphate transport. The results are discussed in relation to a proposed structure of the PstA protein. PMID- 2896189 TI - 13C-NMR studies on the reaction intermediates of porcine kidney D-amino acid oxidase reconstituted with 13C-enriched flavin adenine dinucleotide. AB - The 13C-NMR spectra of the reaction intermediates of D-amino acid oxidase (DAO) were measured with DAO reconstituted with FAD in which the 2-, 4-, 4a-, and 10a positions of the isoalloxazine moiety were selectively 13C-enriched. The reaction intermediates used include charge-transfer complexes of the oxidized DAO with substrate intermediates and those of the reduced enzyme with substrate intermediates. For the former type of complex, the reaction intermediates with beta-cyano-D-alanine (D-BCNA) and D-proline were used, while for the latter the purple intermediates with D-alanine and D-proline were chosen. The 13C-resonances of 2-13C in the reaction intermediates with D-BCNA and D-proline were downfield shifted by about 1 ppm relative to the free oxidized DAO. The 4-13C signal for the DAO-D-BCNA intermediate was observed at 1.2 ppm upfield from that of the oxidized DAO, though that for DAO-D-proline intermediate showed no shift. These results suggest modulation of the hydrogen bondings at C(2) = 0 and/or C(4) = 0 in these reaction intermediates. Comparison of the 13C-resonances of reduced DAO with those of free reduced FMN in the neutral and anionic forms indicate that FAD in reduced DAO is in the anionic reduced form. The 4a-13C resonance of reduced DAO is upfield-shifted by about 3 ppm from that of free reduced anionic FMN. Comparison of the 13C-resonances for the purple intermediates with those of reduced FMN and reduced DAO indicate unequivocally that FAD in the purple intermediate is in the anionic reduced state. The 4a-13C resonances for the purple intermediates were substantially upfield-shifted (by 2.4 ppm with D alanine and 1.9 ppm with D-proline) relative to reduced DAO. This indicates that the electron density, and hence the nucleophilicity, of the 4a-carbon is elevated in the purple intermediate relative to free reduced DAO. This leads to a model in which the oxidative half reaction proceeds via the reaction of molecular oxygen at the 4a-position of the reduced FAD in the purple intermediate. This provides a rational molecular basis for the oxidative half reaction by way of the purple intermediate prior to product release rather than by way of free reduced enzyme after product release. PMID- 2896190 TI - Reconstitution of the proton translocating ATPase from bovine heart mitochondria into planar phospholipid bilayer membranes. AB - Proton translocating ATPase (F0F1) from bovine heart mitochondria was reconstituted into planar phospholipid bilayers, and its electrogenicity was directly demonstrated. The F0F1 ATPase was solubilized using 3-[(3 cholamidopropyl)-dimethylammonio]-1-propanesulfonic acid (CHAPS) as a detergent followed by sucrose density gradient centrifugation according to the method originally described by McEnery et al. for rat liver mitochondria (McEnery et al. (1986) J. Biol. Chem. 259, 4642-4651), with minor modifications. The purified ATPase was reconstituted into proteoliposomes and then reconstituted into planar phospholipid bilayers by the modified fusion method (Hirata et al. (1986) J. Biol. Chem. 261, 9839-9843). A short-circuit current of up to 0.4 pA was induced by adding ATP, and this current was suppressed by the F1 ATPase inhibitor NaN3 or by a specific mitochondrial F0 inhibitor, oligomycin. The direction of the current corresponded to the flow of positive charges from the F1 side to the F0 side. All these facts clearly demonstrate that the mitochondrial F0F1 ATPase was successfully reconstituted into planar phospholipid bilayers, and the current was generated by the ATPase. PMID- 2896191 TI - The membrane-associated ATPase from Sulfolobus acidocaldarius is distantly related to F1-ATPase as assessed from the primary structure of its alpha-subunit. AB - Isolation of novel membrane-associated ATPases, presumably soluble parts of the H+-ATPases, from archaebacteria has been recently reported, and their properties were found to be significantly different from the usual F1-ATPase. In order to assess the relationship of the archaebacterial ATPases to the F1-ATPases and other known ATPases, the amino acid sequence of the alpha subunit of the ATPase from Sulfolobus acidocaldarius, an acidothermophilic archaebacterium, was compared with the sequences of other ATPases. The gene encoding its alpha subunit was cloned from the genomic library of S. acidocaldarius, and the nucleotide sequence was determined. The 591-amino acid sequence deduced from the nucleotide sequence contains a small number of short stretches that shows sequence similarity to the alpha and beta subunits of F1-ATPase. However, the overall similarity is too weak to consider it to be a typical member of the F1-ATPase family when the highly conserved sequences of the F1-ATPase subunits among various organisms are taken into account. Moreover, most of these stretches overlap the consensus sequences that are commonly found in some nucleotide binding proteins. There is no significant sequence similarity to the ion translocating ATPases, which form phosphorylated intermediates, such as animal Na+,K+-ATPases. Thus, the S. acidocaldarius ATPase and probably other archaebacterial ATPases also appear to belong to a new group of ion-translocating ATPases that has only a distant relationship to F1-ATPase. PMID- 2896192 TI - Rate of chase-promoted hydrolysis of ATP in the high affinity catalytic site of beef heart mitochondrial ATPase. AB - Incubation of [gamma-32P]ATP with a molar excess of the soluble, homogeneous ATPase from beef heart mitochondria (F1) results in binding of substrate primarily in a single, very high affinity (KA = 10(12) M-1) catalytic site and in a slow rate of hydrolysis characteristic of single site catalysis. Subsequent addition of millimolar concentrations of nonradioactive ATP as a cold chase, sufficient to fill catalytic sites on the enzyme, results in an acceleration of hydrolysis of bound radioactive ATP of as much as 10(6)-fold, that is, to Vmax rates (Cross, R.L., Grubmeyer, C., and Penefsky, H.S. (1982) J. Biol. Chem. 257, 12101-12105). For this reason, it was proposed that the high affinity catalytic site is a normal catalytic site on the molecule. Recently, Bullough et al. (Bullough, D.A., Verburg, J.G., Yoshida, M., and Allison, W.A. (1987) J. Biol. Chem. 262, 11675-11683) reported that when 5 to 20 microM concentrations of nonradioactive ATP were added as a cold chase to an enzyme-substrate complex consisting of F1 and ATP bound to the high affinity catalytic site, hydrolysis of the chase was commensurate with the turnover rate of the enzyme, whereas the hydrolysis of bound ATP was considerably slower. These authors suggested that the high affinity catalytic site on F1 is not a normal catalytic site. This paper shows, in experiments with a rapid mixing-chemical quench apparatus, that hydrolysis of ATP bound in the high affinity catalytic site is accelerated to Vmax rates following addition of 5 microM ATP as a cold chase. Hydrolysis of bound ATP appears to precede that of the chase. The weight of the available evidence continues to support the original suggestion that the high affinity catalytic site of beef heart F1 is a normal catalytic site. PMID- 2896193 TI - Regulation of acetyl-coenzyme A carboxylase. I. Purification and properties of two forms of acetyl-coenzyme A carboxylase from rat liver. AB - Acetyl-CoA carboxylase of animal tissues is known to be dependent on citrate for its activity. The observation that dephosphorylation abolishes its citrate dependence (Thampy, K. G., and Wakil, S. J. (1985) J. Biol. Chem. 260, 6318-6323) suggested that the citrate-independent form might exist in vivo. We have purified such a form from rapidly freeze-clamped livers of rats. Sodium dodecyl sulfate gel electrophoresis of the enzyme gave one protein band (Mr 250,000). The preparation has high specific activity (3.5 units/mg in the absence of citrate) and low phosphate content (5.0 mol of Pi/mol of subunit). The enzyme isolated from unfrozen liver or liver kept in ice-cold sucrose solution for 10 min and then freeze-clamped has low activity (0.3 unit/mg) and high phosphate content (7 8 mol of Pi/mol of subunit). Citrate activated such preparations with half maximal activation at greater than 1.6 mM, well above physiological range. The low activity may be due to its high phosphate content because dephosphorylation by [acetyl-CoA carboxylase]-phosphatase 2 activates the enzyme and reduces its dependence on citrate. Since freeze-clamping the liver yields enzyme with lower phosphate content and higher activity, it is suggested that the carboxylase undergoes rapid phosphorylation and consequent inactivation after the excision of the liver. The carboxylase is made up of two polymeric forms of Mr greater than or equal to 10 million and 2 million based on gel filtration on Superose 6. The former, which predominates in preparations from freeze-clamped liver, has higher activity and lower phosphate content (5.3 units/mg and 4.0 mol of Pi/mol of subunit, respectively) than the latter (2.0 units/mg and 6.0 mol of Pi/mol of subunit, respectively). The latter, which predominates in preparations from unfrozen liver, is converted to the active polymer (Mr greater than or equal to 10 million) by dephosphorylation. Thus, the two polymeric forms are interconvertible by phosphorylation/dephosphorylation and may be important in the physiological regulation of acetyl-CoA carboxylase. PMID- 2896194 TI - Regulation of acetyl-coenzyme A carboxylase. II. Effect of fasting and refeeding on the activity, phosphate content, and aggregation state of the enzyme. AB - Acetyl-CoA carboxylase isolated from freeze-clamped livers of fed rats has relatively low phosphate content (5.0 mol of Pi/mol of subunit) and high specific activity (3.5 units/mg in the absence of citrate). The enzyme from rats fasted for 12, 18, 24, and 48 h exhibited decreasing specific activities of 2.75, 1.85, 1.7, and 0.9 units/mg, respectively. Citrate activated all preparations of carboxylase, with most activation observed with the least active preparation. There was no significant change in the sensitivity of the enzyme to citrate since half-maximal activation was observed at 0.2 mM for carboxylase from fed as well as fasted rats. With the decrease in activity as a function of fasting, there was a concomitant increase in the phosphate content of carboxylase, with values of 5.3, 5.6, 6.7, and 7.6 mol of Pi/mol of subunit obtained for preparations from rats fasted for 12, 18, 24, and 48 h, respectively. Refeeding the fasted rats resulted in increased specific activity of carboxylase (3.4 units/mg) and decreased phosphate content (5.1 mol of Pi/mol of subunit). Moreover, dephosphorylation by [acetyl-CoA carboxylase]-phosphatase 2 activated the carboxylase from 48-h fasted rats to a value of 2.9 units/mg, assayed in the absence of citrate, indicating that the low activity of carboxylase from fasted rats was due to its increased phosphate content. Superose 6 chromatography showed that the enzyme exists in two polymeric forms, a highly active polymer of greater than or equal to 40 subunits and less active octamer. The former predominates in livers of fed rats, whereas the latter predominates in livers of fasted rats. The octamer could be converted to the highly active polymer by dephosphorylation. These observations indicate that fasting/refeeding results in phosphorylation/dephosphorylation of acetyl-CoA carboxylase with concomitant depolymerization/polymerization of the protein and ultimately decreasing or increasing its specific activity. PMID- 2896195 TI - Evolutionary conservation among biotin enzymes. PMID- 2896196 TI - Mutagenesis of the alpha subunit of the F1Fo-ATPase from Escherichia coli. Mutations at Glu-196, Pro-190, and Ser-199. AB - In an attempt to identify amino acid residues involved in proton translocation by the Fo sector of the Escherichia coli F1Fo-ATPase, 16 mutations at the carboxyl terminal third of the a subunit have been isolated, and their phenotypes have been partially characterized. Thirteen mutations were constructed by "cassette" mutagenesis at two highly conserved residues, aglu196 and apro190. Two mutations were products of oligonucleotide-directed mutagenesis of a portion of of oligonucleotide-directed mutagenesis of a portion of the uncB gene cloned into an M13 vector. One mutation was isolated after in vitro mutagenesis of the entire uncB gene in a plasmid vector with hydroxylamine. Amino acid substitutions for aglu196 (Asp, Gln, His, Asn, Lys, Ala, Ser, Pro) affect ATP-driven proton translocation and passive proton permeability by Fo to varying extents, but do not prevent growth on minimal succinate media. Amino acid substitutions of glutamine or arginine for apro190 affect F1Fo-ATPase assembly and eliminate ATP driven proton translocation, while the substitution of asparagine at this position does not significantly affect either assembly or proton translocation. The substitution of amino acids threonine or alanine for aser199 causes no detectable phenotypic change from wild type. These and other mutations are discussed in terms of the assembly, structure, and function of the a subunit. It is concluded that aglu196 and apro190 are not obligate components of the proton channel, but that they affect proton translocation indirectly. PMID- 2896197 TI - Interaction between Glu-219 and His-245 within the a subunit of F1F0-ATPase in Escherichia coli. AB - Oligonucleotide-directed mutagenesis was used to generate mutations in the a subunit gene (uncB) altering the glutamic acid 219 and the histidine 245 codons. Substitutions of aspartic acid, glutamine, histidine, and leucine for glutamic acid at position 219 neither alter the hydrolytic activity of membrane-bound F1 nor the association of F1 with F0. However, the efficiency of F0-mediated proton translocation was reduced to varying degrees. Replacement of glutamic acid 219 with leucine reduced the ATP-driven proton pumping activity of intact F1F0 to undetectable levels. Roughly 5% of normal activity was observed when glutamine occupied position 219. Surprisingly higher activity, approaching 20% of wild type levels, is seen when histidine replaced glutamic acid 219. The aspartic acid substitution resulted in little loss of enzyme function. Substitution of glutamic acid for histidine 245 results in a reduction to about 45% of normal proton translocation. Construction of the double mutant with substitution of histidine at position 219 and glutamic acid at position 245 yields a complex with better proton translocation than with either mutant separately. The possibility that a functionally important interaction between histidine 245 and glutamic acid 219 of the a subunit may be directly involved in the proton translocation mechanism of F1F0-ATP synthase is discussed. PMID- 2896198 TI - Protease So from Escherichia coli preferentially degrades oxidatively damaged glutamine synthetase. AB - After oxidative damage (e.g. induced with iron, ascorbate, and oxygen), the inactivated glutamine synthetase is selectively hydrolyzed in extracts of Escherichia coli. We therefore tested if glutamine synthetase treated with this system is hydrolyzed preferentially by any of the known E. coli proteases. Protease So, a cytoplasmic serine protease, was found to degrade the oxidized form of glutamine synthetase to acid-soluble peptides 5-10 times faster than the native glutamine synthetase. Degradation of the oxidized glutamine synthetase was inhibited by EDTA and stimulated 5-10-fold by Mg2+, Ca2+, or Mn2+, even though casein hydrolysis by protease So is not affected by divalent cations. Apparently, these cations affect the conformation of this substrate, making it more susceptible to proteolytic attack. Protease Re, another cytoplasmic protease, also degrades preferentially the oxidized form of glutamine synthetase and seems to correspond to the glutamine synthetase-degrading activity recently described by Roseman and Levine [1987) J. Biol. Chem. 262, 2101-2110). However, it is much less active in this reaction than protease So. No other soluble E. coli protease, including Do, Ci, Mi, Fa, Pi, or the ATP-dependent proteases Ti and La (the lon product), appears to degrade this oxidized protein. These results suggest that protease So participates in the hydrolysis of oxidatively damaged proteins and that E. coli has multiple systems for degrading different types of aberrant proteins. PMID- 2896199 TI - Dynein isoforms in sea urchin eggs. AB - Biochemical and immunological analysis of unfertilized sea urchin eggs has revealed the presence of at least two distinct isoforms of cytoplasmic dyneins, one soluble and the other microtubule-associated. The soluble enzyme is a 20 S particle with a MgATPase activity that can be activated 5-fold by nonionic detergents. It contains heavy chain polypeptides that 1) comigrate with the dynein heavy chains of embryonic cilia; 2) cross-react with antibodies against flagellar dynein; and 3) are cleaved by UV irradiation in the presence of MgATP and sodium vanadate into specific peptide fragments. The soluble egg dynein is, therefore, closely related to axonemal dynein and may be a ciliary precursor. Egg microtubule preparations contain a distinct dynein-like polypeptide, previously designated HMr-3 (Scholey, J.M., Neighbors, B., McIntosh, J.R., and Salmon, E.D. (1984) J. Biol Chem. 259, 6516-6525). HMr-3 binds microtubules in an ATP sensitive fashion; it sediments at 20 S on sucrose density gradients, and it is susceptible to vanadate-sensitized UV cleavage. However, HMr-3 can be distinguished from the soluble cytoplasmic dynein on the basis of its weak cross reactivity with antiflagellar dynein antibodies, its heavy chain composition on high resolution sodium dodecyl sulfate-polyacrylamide gel electrophoresis, its low specific ATPase activity, and the molecular weight of its vanadate-induced UV cleavage fragments. HMr-3 may represent a dynein-like polypeptide that is distinct from the pool of ciliary dynein precursors. PMID- 2896200 TI - Functional reconstitution of prostaglandin E receptor from bovine adrenal medulla with guanine nucleotide binding proteins. AB - Prostaglandin E2 (PGE2) was found to bind specifically to a 100,000 x g pellet prepared from bovine adrenal medulla. The PGE receptor was associated with a GTP binding protein (G-protein) and could be covalently cross-linked with this G protein by dithiobis(succinimidyl propionate) in the 100,000 x g pellet (Negishi, M., Ito, S., Tanaka, T., Yokohama, H., Hayashi, H., Katada, T., Ui, M., and Hayaishi, O. (1987) J. Biol. Chem. 262, 12077-12084). In order to characterize the G-protein associated with the PGE receptor and reconstitute these proteins in phospholipid vesicles, we purified the G-protein to apparent homogeneity from the 100,000 x g pellet. The G-protein served as a substrate of pertussis toxin but differed in its alpha subunit from two known pertussis toxin substrate G-proteins (Gi and Go) purified from bovine brain. The molecular weight of the alpha subunit was 40,000, which is between those of Gi and Go. The purified protein was also distinguished immunologically from Gi and Go and was referred to as Gam. PGE receptor was solubilized by 3-[(3-cholamidopropyl)dimethylammonio]-1 propanesulfonic acid and freed from G-proteins by wheat germ agglutinin column chromatography. Reconstitution of the PGE receptor with pure Gam, Gi, or Go in phospholipid vesicles resulted in a remarkable restoration of [3H]PGE2 binding activity in a GTP-dependent manner. The efficiency of these three G-proteins in this capacity was roughly equal. When pertussis toxin- or N-ethylmaleimide treated G-proteins, instead of the native ones, were reconstituted into vesicles, the restoration of binding activity was no longer observed. The displacement of [3H]PGE2 binding was specific for PGE1 and PGE2. Furthermore, addition of PGE2 stimulated the GTPase activity of the G-proteins in reconstituted vesicles. These results indicate that the PGE receptor can couple functionally with Gam, Gi, or Go in phospholipid vesicles and suggest that Gam may be involved in signal transduction of the PGE receptor in bovine adrenal medulla. PMID- 2896201 TI - The interaction of Ca2+ with the calmodulin-sensitive adenylate cyclase from Bordetella pertussis. AB - Bordetella pertussis, the etiologic agent of whooping cough, produces a calmodulin-sensitive adenylate cyclase which elevates intracellular cAMP in a variety of eucaryotic cells. Exogenous calmodulin added to the partially purified adenylate cyclase has been shown to inhibit invasion of animal cells by this enzyme (Shattuck, R. L., and Storm, D. R. (1985) Biochemistry 24, 6323-6328). In this study, several properties of the calmodulin-sensitive adenylate cyclase are shown to be influenced by Ca2+ in the absence of calmodulin. The presence or absence of Ca2+ during QAE-Sephadex ion exchange chromatography produced two distinct chromatographic patterns of adenylate cyclase activity. Two different forms of the enzyme (Pk1 and Pk2EGTA) were isolated by this procedure. Pk1 adenylate cyclase readily elevated intracellular cAMP levels in mouse neuroblastoma cells (N1E-115) while Pk2EGTA adenylate cyclase had no effect on cAMP levels in these cells. Gel exclusion chromatography of Pk1 adenylate cyclase gave apparent Stokes radii (RS) of 43.5 A (+/- 1.3) in the presence of 2 mM CaCl2 and 33.8 A (+/- 0.94) in the presence of 2 mM EGTA [( ethylenebis (oxyethylenenitrilo)]tetraacetic acid). These Stokes radii are consistent with molecular weights of 104,000 (+/- 6,400) and 61,000 (+/- 3,600), respectively. Pk2EGTA adenylate cyclase had an apparent RS of 33.0 (+/- 1.2) (Mr = 60,600 (+/- 2,800] in the presence of Ca2+ or excess EGTA. At 60 degrees C, Pk1 adenylate cyclase exhibited a Ca2+-dependent heat stability with a half-life for loss of enzyme activity of 10.3 min in 5 mM CaCl2 and a half-life of 2.8 min in the presence of 0.1 microM CaCl2. The stability of Pk2EGTA adenylate cyclase was not affected by changes in free Ca2+. The adenylate cyclase preparations described above were submitted to sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, and enzyme activity was recovered from gel slices by extraction with detergent containing buffers. The catalytic subunit isolated from SDS polyacrylamide gels was activated 7-fold in the presence of Ca2+ with maximum activity observed at 1 microM free Ca2+. With both preparations, the apparent molecular weight of the catalytic subunit on SDS gels was 51,000 in the presence of 2 mM CaCl2 and 45,000 in the presence of 2 mM EGTA. The catalytic subunit of the enzyme was purified to apparent homogeneity by preparative SDS-polyacrylamide gel electrophoresis and resubmitted to SDS gel electrophoresis in the presence or absence of free Ca2+. The purified catalytic subunit also exhibited a Ca2+ dependent shift in its mobility on SDS gels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2896202 TI - Sensitive method of detection, quantitation and purification of peptides using pre-column derivatization with phenyl isothiocyanate. AB - A sensitive method for the detection, quantitation and purification of peptides is described. The method is based on pre-column derivatization of peptides with phenyl isothiocyanate to form phenylthiocarbamoyl derivatives (PTC peptides). The derivatized peptides are analysed by reversed-phase high-performance liquid chromatography on a Zorbax ODS column (5 micron) and detected at 269 nm with a sensitivity limit of 1-5 pmol. The technique was utilized for the separation of a mixture of closely related synthetic peptides. The eluted PTC peptides were collected with an average recovery yield of 75% as determined by amino acid analysis. This method of separation of PTC peptides was also combined with the determination of the complete structure of recovered PTC-dynorphin A-(1-13) using the solid-phase sequenator (Sequemat). The advantages of the derivatization method are the rapidity and completeness of the reaction, the stability of the product, the sensitivity and specificity of the detection of derivatized peptides and the compatibility of the technique with subsequent analytical procedures. A particular application of this method was exemplified by the dosage of enkephalins secreted from perfused bovine adrenal glands. PMID- 2896203 TI - Measurement and characterization of somatostatin-14-like immunoreactivity in human urine. AB - Timed urine collections were obtained from normal men and women for a study of somatostatin in urine. Somatostatin-14-like immunoreactivity (S-14 LI) was extracted from urine by adsorption to C-18 silica cartridges, and the extracts were analyzed by RIA directly or after gel and high pressure liquid chromatography (HPLC). S-14 LI was consistently detected in all urine samples. The mean S-14 LI content in 24-h collections in men [10.96 +/- 0.91 (+/- SE) pmol/24 h; n = 10; total volume, 1.96 +/- 0.09 L] was not significantly different from that in women (9.09 +/- 0.85 pmol/24 h; n = 10; total volume, 1.87 +/- 0.09 L). Gel chromatography of 24-h urine collections revealed three major peaks of S 14 LI coeluting with S-14, S-28, and a 12,000 mol wt species corresponding to prosomatostatin. HPLC analysis confirmed the presence of S-14, S-28, and the 12,000 mol wt form and additionally revealed a major fourth peak of 3,000 mol wt, closely related to S-28. Immunoreactivity corresponding to [Des,Ala1]S-14 (S-13) was identified by HPLC coelution with synthetic S-13 and reactivity in a centrally, but not N-terminally directed, S-14 RIA. The relative proportions of the different HPLC peaks varied considerably during the 24-h period. S-14 and S 28 were excreted preferentially during the day, whereas the 12,000 and 3,000 mol wt forms were excreted preferentially at night. The ingestion of a mixed meal evoked parallel increases in plasma S-14 LI and urinary S-14 LI excretion in six normal subjects. We conclude that the principal circulating forms of S-14 LI (S 14, S-28, S-13, and pro-S) are present in urine and that the measurement of urinary S-14 LI could provide a reliable index of integrated plasma S-14 LI concentrations. PMID- 2896204 TI - Hemodynamic effects of flestolol, a titratable short-acting intravenous beta adrenergic receptor blocker. AB - The hemodynamic effects of flestolol were evaluated in 30 patients undergoing routine cardiac catheterization. Hemodynamic measurements were obtained during baseline (prior to flestolol), at steady state during IV flestolol infusion (1, 5, and 10 micrograms/kg/min) and at 20 to 30 minutes after discontinuation (postinfusion). Flestolol-induced hemodynamic changes were similar to those induced by other beta blockers without intrinsic sympathomimetic activity. Significant dose-dependent reduction in heart rate, rate pressure product, and increase in peripheral vascular resistance were seen. Flestolol produced clinically insignificant decrease in myocardial contractility as shown by slight decrease in LVdp/dt, CI, and LVEF. Hemodynamic data from patients with paced heart rate, further confirms a direct mild cardiac depressant effect of flestolol, a finding common to other beta blockers. Consistent with the short elimination half-life of flestolol (t1/2 = 6.5 minutes), most of the hemodynamic changes rapidly returned to preinfusion level within 20 to 30 minutes following its discontinuation. Thus flestolol, with its unique pharmacokinetic profile and titrability, may be beneficial in the treatment of critically ill patients. PMID- 2896205 TI - Catecholaminergic subpopulation of retinal displaced ganglion cells projects to the accessory optic nucleus in the pigeon (Columba livia). AB - In birds, displaced ganglion cells (DGCs) constitute the exclusive source of retinal input to the nucleus of the basal optic root (nBOR) of the accessory optic system. Tyrosine-hydroxylase (TH) immunoreactivity was examined in the pigeon retina after injections of rhodamine-labeled microspheres into the nBOR. A population of about 400 DGCs was observed in each case to exhibit both TH immunoreactivity and rhodamine bead fluorescence. This corresponded to about 10 15% of the total number of identified DGCs in each retina. Double-labeled cells were medium- to large-size (12 to 20 microns in the largest axis) and were always located at the border between the inner nuclear and the inner plexiform layers. Their dendrites could be followed horizontally in lamina 1 of the inner plexiform layer for up to 300 microns from the cell body. The distribution of double labeled DGCs appeared to be mostly peripheral, matching the overall distribution of identified DGCs. Larger DGCs (21-28 microns) were never seen to contain TH immunoreactivity. Examination of brain sections revealed plexuses of thin varicose TH-positive axons in all subdivisions of the nBOR. Unilateral enucleation produced an almost complete elimination of TH immunoreactivity in the contralateral nucleus. Such results suggest the existence of a population of catecholaminergic DGCs projecting into the accessory optic system of the pigeon. They also support the emerging hypothesis concerning the neurotransmitter heterogeneity of ganglion cells in the vertebrate retina. PMID- 2896206 TI - Injection of synthetic human growth hormone-releasing factors in dairy cows. 1. Effect on feed intake and milk yield and composition. AB - Eighteen multiparous Holstein cows in the second half of their lactation were used to determine the effect of human growth hormone-releasing factor (1-44)NH2 and a fragment of growth hormone-releasing factor (1-29)NH2 on lactational performance and feed intake. Saline, the 44-amino acid peptide or the 29-amino acid fragment, at the same dose per injection (.2 nmol.kg-1) was injected intravenously at 4-h intervals for 10 d. Average milk yield, milk composition, feed intake, and feed efficiency were compared for the second half of each 10-d preinjection, injection, and post-injection period. Injections of the 44-amino acid peptide and the 29-amino acid fragment increased milk yield 18.6 and 14.6%, respectively. Feed intake was not changed, but feed efficiency was increased 23.9 and 18.8% over control following 44-amino acid peptide and the 29-amino acid fragment injection, respectively. The lactational response was not different between the two peptides for any of the variables measured. This study demonstrates the feasibility of using a growth hormone-releasing factor fragment as an alternative method of elevating milk yield in cattle via somatotropins. PMID- 2896207 TI - Effect of a new long-acting somatostatin analogue (SMS 201-995) on glycemic and hormonal response to a mixed meal in acromegalic patients. AB - We investigated in 6 acromegalic patients the acute effects on glucose tolerance and insulin secretion of a single sc injection of the somatostatin analogue SMS 201-995, performed 4 h before a mixed meal with xylose administration. Growth hormone levels decreased from 34.0 +/- 20.3 (mean +/- SE) to a minimum of 9.3 +/- 3.0 ng/ml, 3 1/2 h after the injection. A significant inhibition of insulin secretion was also noticed, with a fall from 25.3 +/- 6.4 to 6.3 +/- 2.3 microU/ml at 1 h, and a lower and delayed peak level after the mixed meal. However, the postprandial plasma glucose increase was not different from a control day, while plasma xylose levels were lower. Mean glucagon level after SMS 201-995 was lower than control value in 3 out of the 4 patients in whom it was determined. The decrease of serum growth hormone levels, together with partial glucagon inhibition and, more important, a slowing of intestinal absorptive processes, counterbalanced the inhibitory action of SMS 201-995 on insulin secretion, and no deterioration in carbohydrate tolerance could be demonstrated. However, before SMS 201-995 is employed in the management of acromegalic patients refractory to surgery and bromocriptine therapy, we need further observations of postprandial glycemic profiles during long-term therapy with multiple daily injections of the compound. PMID- 2896209 TI - Immune studies in the depigmenting C57BL/Ler-vit/vit mice. An apparent isolated loss of contact hypersensitivity. AB - Vitiligo is a human disorder which destroys pigment cells in the skin, ears, eyes, and meningeal tissues and has often been associated with a variety of autoimmune disorders. The C57BL/Ler-vit/vit mouse is a mutant strain that exhibits a loss of epidermal pigment cells and a selective cell-mediated immune deficiency to epicutaneous-administered allergens. This observation is consistent with that observed in humans with vitiligo, who also exhibit loss of contact hypersensitivity (CHS), that appears to be associated with loss of pigment cells from the epidermis. Other cellular immune parameters such as delayed type hypersensitivity and antibody generation to both particulate and soluble Ag are normal or even hyperimmune in the vit/vit mice compared with congenic C57BL/6 controls. Cyclophosphamide treatment could reconstitute CHS responsiveness of the vit/vit mice to the allergen dinitrofluorobenzene. Further, this loss of CHS responsiveness to dinitrofluorobenzene could be restored with skin transplants from normal pigmented C57BL/6 mice to vit/vit mice. Normal C57BL/6 mice bearing white skin grafts from vit/vit mice did not contact sensitize. We suggest that this vit/vit mouse strain may serve as an excellent system to investigate various aspects of other contact hypersensitivity reactions as well as vitiligo. PMID- 2896210 TI - The gene for T11 (CD2) maps to chromosome 1 in humans and to chromosome 3 in mice. AB - The chromosomal locations of the human and murine T11 (CD2) gene have been determined. Using recently cloned cDNA to probe Southern blots of mouse X human and Chinese hamster X mouse somatic cell hybrids, we have localized the human T11 gene to chromosome 1 and the murine T11 gene to chromosome 3. Based on previously determined blocks of homology between human chromosome 1 and mouse chromosome 3, it is suggested that the human T11 gene may lie on the short arm of chromosome 1 proximal to p221. Thus, the T11 gene is not linked to any other genes for T cell markers that have been mapped to date. PMID- 2896211 TI - Prerequisite for the induction of lymphokine-activated killer cells from T lymphocytes. AB - Human blood mononuclear cells were separated into Leu-11+7-NK, Leu-11-7+, and Leu 11-7-T cells by means of a combination of the Percoll gradient method and C mediated cytolysis using mAb. When purified Leu-11+7-NK, Leu-11-7+, and Leu-11-7 T cells were cultured with rIL 2 (500 U/ml) for 6 days in a medium supplemented with 10% FCS, Leu-11+7-NK cells responded at the maximum level and Leu-11-7+ cells responded moderately as shown by both cell-proliferation response and cytotoxic activity generated. On the other hand, Leu-11-7-T cells did not respond at all to rIL-2. However, when Leu-11-7-T cells were cultured with rIL-2 in a medium supplemented with 10% autologous serum, they showed considerable responsiveness to rIL-2. In addition, much greater response to Leu-11-7-T cells were produced by the addition of monocytes. Monocyte cytokines, neither IL 1, IFN gamma, TNF, nor their combination were able to substitute for monocytes in the induction culture. In contrast, the response level of Leu-11+7- NK cells remained unchanged irrespective of supplementation with autologous serum to medium or the addition of monocytes to the culture. These results indicated that culture conditions in the experiments significantly affected the results as to determination of lymphokine-activated killer cell precursors, especially the result pertaining to the conversion of T lymphocytes to lymphokine-activated killer cells. Under appropriate conditions, not only NK cells but also T cells are important precursors of lymphokine-activated killer cells. PMID- 2896208 TI - Regulation of thyroid-stimulating hormone (TSH) secretion in the fetus and neonate. PMID- 2896212 TI - A flexible peptide spacer increases the efficacy of holoricin anti-T cell immunotoxins. AB - Immunotoxins, constructed by chemically cross-linking an antibody and protein toxin, do not possess the high efficacy of the native toxin. Decreases in toxicity are due in part to the steric constraints imposed on the two macromolecules, which result in both decreased antibody binding and toxin function. In examining the structural features that influence efficacy in holotoxin-antibody conjugates, it was found that the incorporation of a 29 residue polypeptide, derived from the insulin B chain between the antibody and ricin moiety, resulted in an increase in both potency and efficacy. In a murine model system, potency of the peptide spacer conjugate was increased nearly 10 fold; however, when examined by the procedure used to purge bone marrow, the peptide spacer conjugate was not demonstrably more toxic to nontarget cells than the nonspacer conjugate. Thus, in addition to increases of efficacy and potency, this novel immunotoxin demonstrated increased specificity by approximately 10 fold. To test the general utility of peptide spacer inclusion, a T101-ricin conjugate was constructed with the peptide spacer. It yielded a protein synthesis inhibition rate of -0.6 log/h on MOLT-3 cells, greater than 10-fold more efficacious than a previously constructed nonspacer T101-ricin conjugate examined under similar conditions. PMID- 2896213 TI - IL-4-induced lymphokine-activated killer cells. Lytic activity is mediated by phenotypically distinct natural killer-like and T cell-like large granular lymphocytes. AB - The purpose of the current study was to characterize lymphokine-activated killer (LAK) activity induced with IL-4/B cell stimulatory factor-1 and to compare IL-4 induced LAK activity with IL-2-induced LAK activity. Culture of murine lymphocytes with high concentrations of IL-4 induced nonspecific lytic activity against a wide variety of tumors. Lytic activity induced by IL-4 increased with increasing concentrations of IL-4 over the range of 1.0 to 25 ng/ml. The kinetics of LAK induction by IL-4 and IL-2 were similar; however, IL-4 was less effective than IL-2 in maintaining lytic activity for longer culture periods and provided lower viable cell yields than did IL-2. Similar to IL-2, IL-4 induced blastogenesis and the generation of large granular lymphocytes, all LAK activity observed was exclusively associated with the large granular lymphocyte fraction, and the cytolytic effector cells were heterogeneous in regards to cell surface phenotype. The majority of IL-4-induced lytic activity was associated with mutually exclusive NK-like (i.e., NK-1.1+ Lyt-2-) and T cell-like (i.e., NK-1.1- Lyt-2+) LAK cells. The precursors for each subset were distinct and expressed the asialo-GM1+ Lyt-2- and the asialo-GM1+ Lyt-2+ phenotypes, respectively. Although IL-4-induced LAK effector cells were morphologically and phenotypically similar to IL-2-induced LAK cells, IL-2 generated equivalent numbers of T cell-like and NK-like LAK cells, whereas IL-4 generated 3.5-fold more T cell-like LAK cells than NK-like LAK cells. It might eventually be possible to exploit the preferential activation of T cell-like LAK by IL-4 for therapeutic advantage. PMID- 2896214 TI - Anti-CD2 monoclonal antibodies and calcium ionophore A23187 modulate lytic activity in CD4+ and CD8+ alloreactive clones. AB - Alloreactive cytolytic clones can be modified in terms of their lytic specificity by several agents. We have evaluated the effects of anti-CD2 and anti-CD3 mAb and the calcium ionophore A23187 on CD4+ and CD8+ allospecific cytolytic clones. All these agents can modify the specificity of clones although the range of targets lysed depends on the agent used and subtype of the clone. Inhibition studies suggest that surface structures that are involved in non-specific cell-cell interaction processes play a role in this non-MHC-restricted cytolysis. PMID- 2896215 TI - Hormone receptors on cloned T lymphocytes. Increased responsiveness to histamine, prostaglandins, and beta-adrenergic agents as a late stage event in T cell activation. AB - Lymphocytes have surface receptors for a variety of hormones that play an important part in modulating the immune response. Most previous studies, however, have examined the effects of hormone agonists on heterogeneous bulk populations of cells, making it difficult to precisely identify the responding target cells. We have therefore studied a set of well characterized T cell clones for a series of adenylate cyclase-linked hormone receptors and examined changes in receptor expression that occur after cell activation. All clones tested had receptors for histamine, isoproterenol, and PGE1, but not for several other cAMP-active hormone agonists. The apparent receptor affinities and their specificities were characteristic of typical histamine H2, beta 2-adrenergic, and PGE receptors. The cAMP response to PG was higher and longer lasting than that to histamine or isoproterenol, both of which appear to undergo receptor desensitization. After activation of quiescent cells in IL-2-containing media, the cAMP response to all three ligands increased, peaking 4 to 5 days after stimulation, and then returned to basal levels as the cells ceased proliferating. Inasmuch as this effect did not require Ag, it appears that the coordinate regulation of responsiveness to these ligands is a direct result of lymphocyte activation. This increase in hormone receptor activity is functionally analogous to the up-regulation of receptors for other ligands that occurs after lymphocyte activation and further demonstrates the important immunoregulatory role played by the changing repertoire of surface receptors that is associated with activation. PMID- 2896216 TI - Induction and regulation of CD2 mRNA in human lymphocytes. AB - Herein we studied the accumulation and decay of CD2 mRNA in human PBMC stimulated with PHA. The data show that CD2-specific messages are present in low quantities in resting PBMC and are rapidly increased by five- to sevenfold within 24 h of addition of optimal amounts of PHA. Similar induction of CD2 mRNA was seen after stimulation of PBMC with anti-CD3 mAb and PMA. Peak levels of CD2 message were maintained until 72 h post-stimulation and declined gradually thereafter. Despite stimulation with Staphylococcus aureus and PMA, purified B cells failed to demonstrate any CD2 mRNA. Unlike transferrin or IL-2R mRNA, Il-2 had no effect on the accumulation of CD2 messages in resting or PHA-stimulated PBMC. The time course of CD2 mRNA accumulation preceded lymphocyte proliferation and the appearance of additional cell surface CD2 Ag. The decay of CD2 mRNA was very rapid, with a t 1/2 of approximately 45 min. The protein synthesis inhibitor, cycloheximide, increased its half-time by fourfold to 3.5 h. The data imply the existence of a labile factor, dependent on protein synthesis that is important in the regulation of CD2 mRNA. Compared to other PHA-inducible lymphocyte genes, the kinetics of CD2 transcript accumulation are most reminiscent of the oncogenes N ras and c-abl. PMID- 2896217 TI - Thy-1+ dendritic epidermal cells in mice: precursor frequency analysis and cloning of concanavalin A-reactive cells. AB - Bulk cultures of mouse Thy-1+ dendritic epidermal cells (Thy-1+ DEC) have been shown to proliferate in response to concanavalin A (Con A) and IL-2, to secrete IL-2-like growth factors, and to lyse target cells such as YAC-1. Limiting dilution microculture was utilized in order to determine the precursor frequency of Con A-responsive Thy-1+ DEC in suspensions of AKR/J epidermal cells as well as whether these several functional activities all reside within a single Thy-1+ DEC precursor. Precursor frequency analysis of cultures established with limiting numbers of FACS-purified Thy-1+ DEC, irradiated syngeneic splenic filler cells and exogenous IL-2 indicated that approximately 20% of Thy-1+ DEC proliferated in response to Con A. Parallel microcultures in which purified Thy-1+ DEC were plated at a density of 0.5 cells/well were used to establish clones. Twenty clones were characterized phenotypically, and ten of these were also tested for their capacities to proliferate in response to Con A or IL-2, to secrete IL-2 like growth factors, and to exhibit cytotoxicity. All clones were Thy-1+ and L3T4 , but while most were also Lyt-2-, several contained 3%-18% dull Lyt-2+ cells. Functional studies revealed that each clone displayed all of the above functional activities, albeit with substantial quantitative variation. Clones with the highest cytotoxic activity had relatively low responsiveness to Con A or IL-2 and included all clones containing dull Lyt-2+ cells; conversely, clones with the highest proliferative responses had relatively low cytotoxic activity and were all Lyt-2-. This degree of functional and phenotypic heterogeneity among cloned Thy-1+ DEC may reflect their particular states of activation or differentiation; whether it reflects the biologically relevant in vivo activities of these cells must still be determined. PMID- 2896218 TI - Ratio of Langerhans cells to Thy-1+ dendritic cells in contact hypersensitivity. PMID- 2896220 TI - Transient elevation of serum bile acids during acute pancreatitis. AB - An increase of serum bile acids was detected in patients with biliary acute pancreatitis who could be investigated during the first 24 hours after the onset of the acute phenomena. Serum bile acids levels, as well as alpha-amylase activity, however rapidly decreased and were found within normal limits after 48 72 h, while the increased serum gamma-glutamyltransferase activity persisted for at least 7 days. Changes affecting serum bile acids in patients with acute pancreatitis unassociated to biliary disease or in patients with acute biliary disease unaccompanied by a pancreatic reaction were less important. Mechanisms leading to these changes and their possible pathogenic relevance are briefly discussed. PMID- 2896219 TI - Travelers' diarrhea in West Africa and Mexico: fecal transport systems and liquid bismuth subsalicylate for self-therapy. AB - The goals of this study were threefold: to compare the etiology of travelers' diarrhea in West Africa and Mexico, to evaluate two fecal transport systems for the recovery of enteropathogens, and to verify the efficacy of liquid bismuth subsalicylate (BSS) in different locations and under different entrance criteria for disease severity. The study populations consisted of 133 European tourists in West Africa and 112 American students in Mexico who had suffered from travelers' diarrhea. In 60% and 38% of the stool samples at the two study sites, similar proportions of enteropathogens were detected. A two-vial system consisting of Enteric Plus medium and polyvinyl alcohol fixative was slightly superior for identifying enteric pathogens than was a three-vial system with buffered glycerol saline, Cary-Blair medium with campylobacter antibodies, and polyvinyl alcohol fixative. In a parallel, double-blind, randomized trial, BSS significantly shortened disease duration at both study sites. PMID- 2896222 TI - The presence of adult T cell leukemia virus proviral DNA in pregnant healthy carriers and the absence of proviral DNA in neonates born to carrier mothers. PMID- 2896221 TI - Influence of cold challenge on finger skin temperature during long-term use of beta-adrenoceptor blocking drugs in hypertensive patients. AB - Because complaints of cold extremities are a frequent side effect of beta adrenoceptor blocking drugs, we assessed Finger Skin Temperature (FST) during a standardized Finger Cooling Test (FCT) in 51 normals and in 50 hypertensive patients after long term treatment with beta-adrenoceptor blockers. In the 29 hypertensive patients with complaints of cold extremities the recovery of FST after cold challenge was significantly worse as compared to the 21 hypertensive patients without complaints. Hypertensive women who used beta-adrenoceptor blocking agents showed lower FST-values after the cold test in comparison to hypertensive men. No difference in recovery of FST were found between the users of non-selective and selective beta-adrenoceptor blockers. We conclude that the FCT is a suitable method to detect a decreased ability of vasodilate during chronic beta-adrenoceptor blockade in hypertensive patients. PMID- 2896223 TI - Variable reduction in beta-adrenergic sweat secretion in cystic fibrosis heterozygotes. AB - Because patients with cystic fibrosis (CF) consistently lack sweating response to isoproterenol (ISO) in vivo and in vitro, we studied to what extent beta adrenergic defect is expressed in CF heterozygotes. To improve the sensitivity and accuracy of determining the sweating response to intradermal ISO (also containing theophylline and atropine), a water vapor analyzer was used, and the peak sweat rates attained after intradermal injection in the forearm of optimal concentrations of ISO and methacholine (MCH) were determined. The peak ISO sweat rate was further normalized by the peak MCH sweat rate in each individual and expressed as the relative ISO sweat ratemax (in percent). The relative ISO sweat ratemax was determined independent of age and sex and was unchanged after brief acclimatization. The mean relative ISO sweat ratemax of CF heterozygotes was significantly lower than that of controls (10.1% vs 19.5%); however, 21 of the 54 CF heterozygotes overlapped with controls, and the remainder of the CF heterozygotes fell below the arbitrary demarcation line drawn at the relative sweat rate of around 10%. Thus, although the ISO sweat test may not be a practical discrimination test for CF heterozygotes, knowledge of the diversity of beta-adrenergic sweating responses in CF heterozygotes will provide a useful data base for further understanding the possible linkage (or its absence) between the abnormal CF gene(s) (which may be identified by molecular biologists in the near future) and the abnormal intracellular process(es) that takes place during beta adrenergic stimulation of the CF eccrine sweat gland. PMID- 2896224 TI - Single stage repair for severe hypospadias. PMID- 2896225 TI - Release of pertussis toxin and its interaction with outer-membrane antigens. AB - The absence of subunit S3 in cell-associated pertussis toxin (PT) from a mutant of Bordetella pertussis which failed to produce cell-free toxin suggested that this subunit was involved in the release of PT into the culture medium. The addition of methylated beta-cyclodextrin (MCD) to the culture medium caused a small but consistent increase in the release of lipopolysaccharide (LPS) by four wild-type strains of B. pertussis. Since previous studies have shown that MCD also enhances the levels of PT in culture supernates, it seemed probable that the increased shedding of outer-membranes vesicles (OMV) may explain the increased levels of both cell-free PT and LPS. Release of PT was inhibited in media buffered with HEPES but was unaffected in Tris/HC1 buffer. This suggested that in addition to shedding of the outer membrane, increased permeability and greater destabilization of the outer membrane, as caused by Tris/HC1 buffer, may be important in the release of PT. Our data do not support the idea that PT is packaged into OMV because only an insignificant proportion (0.01%) of the total cell-free PT was associated with LPS. The association of PT with small micelles derived from outer-membrane amphiphiles may be more important since the LPS content of PT purified from culture supernates (containing no large OMV) was nearly 18% by weight. PMID- 2896226 TI - Coordinated regulation of ammonium assimilation and carbon catabolism by glyoxylate in Saccharomyces cerevisiae. AB - The activities of citrate synthase (EC 4.1.3.7) and NADP+-dependent glutamate dehydrogenase (GDH) (EC 1.4.1.4) of Saccharomyces cerevisiae were inhibited in vitro by glyoxylate. In the presence of glyoxylate, pyruvate and glyoxylate pools increased, suggesting that glyoxylate was efficiently transported and catabolized. Pyruvate accumulation also indicates that citrate synthase was inhibited. A decrease in the glutamate pool was also observed under these conditions. This can be attributed to an increased transamination rate and to the inhibitory effect of glyoxylate on NADP+-dependent GDH. Furthermore, the increase in the ammonium pool in the presence of glyoxylate suggests that NADP+-dependent GDH was being inhibited in vivo, since the activity of glutamine synthetase did not decrease under these conditions. We propose that the inhibition of both citrate synthase and NADP+-dependent GDH could form part of a mechanism that regulates the internal 2-oxoglutarate concentration. PMID- 2896227 TI - A comparison of methodologies for the study of functional transmitter neurochemistry in human brain. AB - A number of different approaches to the study of functional neurochemistry in human brain are discussed. The advantages and disadvantages of three main techniques are contrasted: (i) using animal tissue preparations as models of the human brain; (ii) using human peripheral tissue preparations as models of dynamic CNS processes; and (iii) studying human tissue, obtained postmortem, directly. Animal models are often readily obtained and reliable, and the high degree of inbreeding of common laboratory animals ensures that they usually yield consistent results. However, there are a number of human disorders for which animal models are either poor or unavailable, and species differences make extrapolation from the animal to the human case difficult. Human peripheral tissue models rely on a degree of homology between peripheral and CNS processes; in most cases, the evidence for such homologies derives from animal, rather than human, studies. Moreover, several examples are known where a peripheral process mimics the equivalent glial cell activity more closely than the neuronal, which can be a serious drawback for studies of neurotransmission. The use of postmortem human brain tissue presents a number of obvious difficulties, resulting from variations in the patient's age, agonal state, sex, preterminal medication, postmortem delay, etc. Human beings are genetically and nutritionally heterogeneous, so that data variability is usually greater here than when using tissue from laboratory animals. However, it is possible to control for a number of these factors, for example, by matching samples for basal metabolic rate and tissue integrity, and recently developed tissue freezing and storage techniques permit the use of within-subject experimental designs to help reduce experimental variation. A range of neurotransmitter functions are well retained in such tissue samples, so that regional variations, differential transmitter activities, drug effects, etc., can be studied in normal tissue samples, as well as in samples taken from cases of neurological and psychiatric disease. This allows, for example, changes in neuroanatomical indices to be correlated with localised alterations in a specific neurotransmitter function. A systematic approach to the analysis and matching of tissue samples is advocated. The three approaches should be considered to be complementary, especially for the study of human brain diseases. PMID- 2896228 TI - Long-term changes in rat brain tyrosine hydroxylase following reserpine treatment: a quantitative immunochemical analysis. AB - An immunoblot procedure was developed to quantify the amount of tyrosine hydroxylase protein in homogenate of small brain regions. With the use of this method we have studied the variations in tyrosine hydroxylase activity and protein levels in some catecholaminergic neurons at different times following a single reserpine injection (10 mg/kg s.c.) and reevaluated the anatomical specificity of tyrosine hydroxylase induction by this drug. Reserpine administration provoked a long-lasting increase in both tyrosine hydroxylase activity and protein levels within locus ceruleus neurons. This effect culminated at day 4 after injection. At this time, the enzyme activity and protein levels in treated animals were respectively 2.7 and 2.6 times that measured in vehicle treated animals. Both parameters varied in parallel so that tyrosine hydroxylase specific activity did not change over time. In contrast, reserpine did not cause any changes in tyrosine hydroxylase activity in the dopaminergic neurons of the substantia nigra, but provoked a moderate increase in tyrosine hydroxylase protein level. This latter effect was maximal (1.5 times) 4 days after treatment. In the adjacent dopaminergic area, i.e., the ventral tegmental area, a small decrease in the enzyme activity was recorded at day 2 without any significant change in the level of the protein. In conclusion, first, our data show the capacity of our method to assay tyrosine hydroxylase protein amounts in small brain catecholaminergic nuclei. Second, our results confirm and extend previous studies on the effect of reserpine on the regulation of tyrosine hydroxylase level within brain noradrenergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896229 TI - Cellular location of glutamine synthetase and lactate dehydrogenase in oligodendrocyte-enriched cultures from rat brain. AB - Glial cells were isolated from 1-week-old rat brain and cultured in a serum-free medium supplemented with the hormones insulin, hydrocortisone, and triiodothyronine. After 1 week in culture the cell population consisted mainly of galactocerebroside-positive cells (GC+; oligodendrocytes), the remainder of the cells being positive for glial fibrillary acidic protein (GFAP+; astrocytes). Oligodendrocytes were selectively removed from the cultures by complement mediated cytolysis. The activities of glutamine synthetase and of various marker enzymes were measured in the nonlysed cells remaining after complement treatment of the cultures and in the culture medium containing proteins of the lysed cells. We found that the cellular activity of glutamine synthetase decreased in parallel with the lysis of GC+ cells and that the activity of glutamine synthetase in the supernatant increased. The activity of glycerol-3-phosphate dehydrogenase, a marker enzyme for oligodendrocytes, was no longer detectable in complement treated cultures and the activity of glutamine synthetase was markedly lowered, whereas the activity of lactate dehydrogenase was as high as in untreated cultures. The location of glutamine synthetase both in oligodendrocytes and in astrocytes was confirmed by double-label immunocytochemistry with antisera against glutamine synthetase, GC, and GFAP. We conclude that in this culture system glutamine synthetase is expressed in both types of glial cells and that the activity of lactate dehydrogenase is at least one order of magnitude higher in astrocytes than in oligodendrocytes. PMID- 2896230 TI - Histamine increases phospholipid methylation and H2-receptor-adenylate cyclase coupling in rat brain. AB - Histamine stimulated the enzymatic synthesis of phosphatidylcholine from phosphatidylethanolamine in crude synaptic membranes of rat brain containing the methyl donor S-adenosyl-L-methionine (SAM). In the presence of, but not in the absence of SAM, histamine increased cyclic AMP accumulation at the concentrations that stimulate phospholipid methylation. S-Adenosyl-L-homocysteine, an inhibitor of phospholipid methyltransferases, inhibited histamine-stimulated phospholipid methylation and histamine-induced cyclic AMP accumulation in the presence of SAM in a concentration-dependent manner. Histamine-induced [3H]methyl incorporation into phospholipids exhibited a marked regional heterogeneity in rat brain in the order of cortex greater than medulla oblongata greater than hippocampus greater than striatum greater than midbrain greater than hypothalamus. The regional distribution of histamine-induced cyclic AMP accumulation exactly paralleled histamine-stimulated [3H]methyl incorporation in rat brain. Histamine-induced cyclic AMP accumulation was inhibited by the addition of cimetidine or famotidine, but not by mepyramine or diphenhydramine. The accumulation of cyclic AMP in the presence of SAM was observed by the addition of impromidine or dimaprit, but not by 2-pyridylethylamine. These results indicate that phospholipid methylation is induced by histamine and may participate in H2 receptor-mediated stimulation of adenylate cyclase in rat brain. PMID- 2896231 TI - Utilization of the synthetic phosphagen cyclocreatine phosphate by a simple brain model during stimulation by neuroexcitatory amino acids. AB - The ability of 1-carboxymethyl-2-imino-3-phosphonoimidazolidine (cyclocreatine P), accumulated by a simple brain model, to function as a supplemental synthetic phosphagen and respond to the decreases in cytosolic ATP/free ADP ratios that occur during prolonged stimulation by various excitatory amino acids was investigated. Suspensions of chopped whole brain from 11- to 14-day-old chick embryos were incubated with 30 mM cyclocreatine for 90 min, resulting in accumulation of 100 mumol/g dry weight of cyclocreatine-P, and then incubated for up to 1 h with a series of excitatory amino acids of widely differing potencies. Under these conditions net utilization of cyclocreatine-P was detected in response to stimulation by the following neuroexcitatory compounds at the indicated threshold concentrations: kainate (20 microM), N-methyl-DL-aspartate (20 microM), L-homocysteate (20 microM), L-glutamate (200 microM), D-glutamate (200 microM), L-aspartate (2 mM), DL-2-amino-3-phosphonopropionate (2 mM), and DL 2-amino-4-phosphonobutyrate (2 mM). Significant increases in water content of chick embryo brain minces accompanied stimulation by excitatory amino acids. It is suggested that changes in water content or cyclocreatine-P levels in this sensitive brain model might be utilized in automatable screening procedures for detecting novel antagonists and/or new agonists of excitatory amino acids. PMID- 2896232 TI - Prenatal diagnosis and carrier detection of genetic diseases by analysis of deoxyribonucleic acid. PMID- 2896233 TI - Carrier detection in typical and atypical X-linked agammaglobulinemia. AB - We have recently demonstrated that B cells from obligate carriers of typical X linked agammaglobulinemia (XLA) exhibit nonrandom X chromosome inactivation. The active X is always the X that does not carry the gene defect. To determine if this were also true in carriers of atypical XLA and to provide carrier detection for all women at risk of being carriers of XLA, we developed a technique that permits analysis of X chromosome inactivation in cells from any woman. This technique combines the production of somatic cell hybrids that selectively retain the active X chromosome with the use of X-linked restriction fragment length polymorphisms that permit the distinction of the two X chromosomes. Three obligate carriers of typical XLA and four women whose sons might be considered to have atypical or sporadic XLA were studied. B cell hybrids from all seven women demonstrated exclusive use a single X as the active X. In addition, B cell hybrids from four of eight women at 25% or 50% risk of being carriers exhibited nonrandom X chromosome inactivation, indicating that these women were also carriers of X-linked forms of hypogammaglobulinemia. These results illustrate a technique that can be used both to help define XLA and to provide carrier detection for all women at risk of being carriers of this disorder. PMID- 2896235 TI - Use of conditioned taste aversion as a conflict model: effects of anxiolytic drugs. AB - Moderate taste aversions were induced by pairing the initial consumption of 0.25% sodium saccharin (SACC) with either 25 mg/kg i.p. l-5-hydroxytryptophan or 30 mg/kg i.p. LiCl. The expression of these moderate conditioned SACC aversions was antagonized by pretreatments (i.p. or p.o.) with benzodiazepine and non benzodiazepine anxiolytic drugs (lorazepam, diazepam, chlordiazepoxide, oxazepam, phenobarbital, meprobamate, and chlormezanone). Chlordiazepoxide produced less or no antagonism of the expression of stronger SACC aversions induced by 50 or 75 mg/kg l-5-hydroxytryptophan or by 60 or 90 mg/kg LiCl. Nonanxiolytic drugs, including dipsogenic compounds that increased the water intake of hydrated rats (2 M NaCl i.p.; isoproterenol HCl s.c.; and histamine diphosphate s.c.), and even additional 24 hr of fluid deprivation did not antagonize the expression of moderate conditioned taste aversions, indicating that anxiolytic drugs have a very selective effect and that they do not appear to act through homeostatic drinking mechanisms. An essential feature of the taste aversion conflict model is that thirsty rats encounter only SACC. When water was conspicuously available in addition to SACC in two-bottle tests, neither chlordiazepoxide nor phenobarbital antagonized the expression of conditioned taste aversion. Thus, anxiolytic drugs do not produce amnesia for the conditioned aversion, but attenuate the ability of conditioned SACC aversion to suppress SACC consumption in one-bottle tests. The antagonism of the expression of conditioned taste aversion measured with a one bottle testing method offers a simple, sensitive, and selective screen for anxiolytic drugs. A possible mechanism by which anxiolytics increase both suppressed as well as unsuppressed fluid consumption is discussed. PMID- 2896234 TI - Inhibition of nucleic acid synthesis in P-388 lymphocytic leukemia tumor cells by helenalin and bis(helenalinyl)malonate in vivo. AB - Although the parent sesquiterpene lactone, helenalin, and its derivative, bis(helenalinyl)malonate, are structurally related chemically, they demonstrate differences in their antineoplastic activity, with bis(helenalinyl)malonate being much more active against P-388 lymphocytic leukemia cell growth (T/C% = 261) compared with helenalin (T/C% = 162). Previous studies have shown that both agents strongly inhibit protein synthesis in vivo by greater than 70% after 3 d of administration and in vitro by 50% at a 100 microM concentration of drug. This inhibition of protein synthesis of P-388 cells may be partially responsible for the cytotoxicity of the drug. These agents also inhibit nucleic acid synthesis in vivo, with DNA synthesis being suppressed by greater than 90% after 2 d of administration of drugs at the therapeutic dose. Of the sulfhydryl-bearing enzymes involved in nucleic acid synthesis that were assayed, only the activities of inosine-5'-monophosphate (IMP) dehydrogenase and the ribonucleotide reductase complex were inhibited by greater than 50% by these sulfhydryl-reactive drugs, which would account for the observed inhibition of nucleic acid synthesis in the P-388 cells. The inhibition of the activities of these enzymes lowered the deoxyribonucleotide levels in P-388 cells, which would explain the overall suppression of DNA synthesis by the sesquiterpene lactones. PMID- 2896237 TI - Differences in the effects of alpha-1 adrenergic blockade with prazosin and indoramin on coronary blood flow during exercise. AB - This study compared the effects of two selective alpha-1 adrenergic blockers, prazosin and indoramin, on the response of coronary blood flow and myocardial oxygen consumption during treadmill exercise in chronically instrumented dogs. Left circumflex coronary artery blood flow was measured with an electromagnetic flowmeter, whereas myocardial arteriovenous oxygen difference was determined with indwelling aortic and coronary sinus catheters. During control conditions, coronary blood flow, arteriovenous oxygen extraction and myocardial oxygen consumption increased regularly with exercise. Both prazosin and indoramin decreased arterial pressure at rest and during exercise, but during heavier levels of exercise blood pressure was lower and heart rates were higher after prazosin. Prazosin did not alter myocardial oxygen consumption, whereas indoramin tended to decrease oxygen consumption; myocardial oxygen consumption was significantly less after indoramin than after prazosin during the heaviest levels of exercise. Prazosin, but not indoramin, significantly decreased coronary vascular resistance both at rest and during exercise, and blunted the decrease in coronary sinus oxygen tension which occurred during exercise. In comparison with prazosin, during heavy exercise coronary blood flow was significantly decreased, myocardial oxygen extraction significantly increased and myocardial oxygen consumption significantly decreased after indoramin. PMID- 2896236 TI - Somatostatin inhibits cAMP-dependent and cAMP-independent calcium influx in the clonal pituitary tumor cell line AtT-20 through the same receptor population. AB - The characteristics of somatostatin (SRIF) inhibition of calcium influx stimulated by corticotropin releasing factor (CRF), an activator of adenylate cyclase, and K+, a membrane depolarizing agent, in AtT-20 cells were assessed. Changes in cytosolic calcium levels were measured using the fluorescence probe Quin 2. Both CRF and K+ raise cytosolic calcium levels by stimulating calcium influx. SRIF induced an immediate inhibition of CRF and K+-stimulated calcium influx. This effect was concentration-dependent with IC50 values for SRIF's blockade of CRF and K+ stimulation of 64 +/- 13 pM and 100 +/- 15 pM, respectively. The SRIF analogs, SRIF 28, Trp8-SRIF and Tyr11-SRIF had the same rank order of potency to block CRF and K+-induced calcium influx. The inhibitory effects of SRIF on AtT-20 cells were abolished by pertussis toxin pretreatment. SRIF inhibition of both CRF and K+-induced calcium influx desensitized. The desensitization was rapid (T1/2 approximately 2.5 min), dependent on the concentration of SRIF and not due to the degradation of the peptide. The ability of SRIF to block CRF (cyclic AMP-dependent) and K+ (cyclic AMP-independent) stimulated calcium influx into AtT-20 cells cannot be separated. PMID- 2896238 TI - Increment of calmodulin in proportion to enhancement of non-nicotinic responses after preganglionic stimulation of the dog cardiac sympathetic ganglia. AB - The possible involvement of calmodulin in ganglionic function was investigated. Drugs were given directly into the cardiac sympathetic ganglia through the right subclavian artery (i.a.), unless otherwise stated. Positive chronotropic responses to angiotensin II (0.1 and 0.2 micrograms) were enhanced after repetitive high frequency preganglionic stimulation to the right stellate ganglion. After the stimulation, positive chronotropic responses to bethanechol (2.5, 5 and 10 micrograms), but not those to dimethylphenylpiperazinium (2.5, 5 and 10 micrograms), also were enhanced. The enhancement of response to angiotensin II was not affected by i.v. pretreatment with hexamethonium (40 mg/kg) plus atropine (1 mg/kg) or nifedipine (1 mg/kg). Responses to angiotensin II were not enhanced by A23187 (0.3 mg). The enhanced response to angiotensin II after the stimulation was reduced by the calmodulin antagonists, trifluoperazine (0.1, 0.2 and 0.4 mg) and by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (0.5, 1 and 2 mg), but not by promethazine (1 mg) and N-(6-aminohexyl)-1 naphthalenesulfonamide (0.5, 1 and 2 mg). The enhanced response to bethanechol after the stimulation also was inhibited by N-(6-aminohexyl)-5-chloro-1 naphthalenesulfonamide. Pretreatment with N-(6-aminohexyl)-5-chloro-1 naphthalenesulfonamide before the stimulation prevented development of the enhancement in responses to the peptide. The inhibition of endogenous protein synthesis by cycloheximide, 2.5 or 5 mg/kg i.v. 6 hr before surgical procedures, strongly inhibited development of the enhancement in responses to angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896240 TI - Central nervous system site of action for the hypotensive effect of clonidine in the cat. AB - The purpose of our study was to determine whether clonidine exerts its centrally mediated hypotensive action at three sites that influence arterial pressure located in the medulla, specifically associated with the intermediate area of the ventrolateral medulla. The "intermediate area" lies approximately 1.5 mm caudal to the border of the trapezoid body (caudal border) and 4 mm lateral to the midline. One of the sites that influence arterial pressure lies in the nucleus reticularis rostroventrolateralis. The second site lies in close proximity to the rostral part of the nucleus reticularis lateralis (rLRN) and also near the A1 area. The third site lies in the most rostral area and medial to the nucleus reticularis rostroventrolateralis, that is in the nucleus paragigantocellularis lateralis. Unilateral microinjections of 0.22 and 0.43 nmol of clonidine into the rLRN produced dose-dependent decreases in arterial pressure. The 0.43 nmol dose of clonidine had no effect when unilaterally or bilaterally microinjected into either the nucleus reticularis rostroventrolateralis or into the nucleus paragigantocellularis lateralis. Microinjection of the alpha-2 adrenoceptor antagonist, idazoxan (16.6 nmol), unilaterally into rLRN had no effect per se, but prevented the hypotensive effect of a subsequent microinjection of clonidine. Similarly, bilateral microinjection of idazoxan into rLRN counteracted the hypotensive effect of i.v. administered clonidine. These data indicate that clonidine acts at alpha-2 adrenoceptors in the rLRN to produce hypotension. PMID- 2896239 TI - A peripherally acting alpha-2 adrenoceptor antagonist: L-659,066. AB - L-659,066 has been characterized as a potent and selective alpha-2 adrenoceptor antagonist. Both in vitro and in vivo, L-659,066 exhibited specificity (comparable to rauwolscine) for alpha-2 over alpha-1 adrenoceptors. Studies comparing L-659,066 with a previously described antagonist, L-657,743, demonstrate that the new compound penetrates the blood-brain barrier only poorly after systemic administration. With a pA2 of 8.44 at alpha-2 adrenoceptors in the isolated rat vas deferens and an IC50 of 3.0 nM against the binding of [3H]rauwolscine to rat cerebrocortical membranes, L-659,066 possessed, respectively, about one-eighth and one-third of the potency of L-657,743. Similar relative potencies were obtained in vivo in pithed rats with regard to blocking peripherally located postjunctional and prejunctional alpha-2 adrenoceptors (L 659,066 = one-seventh and one-fourth of L-657,743, respectively). In tests carried out in vivo with rats for ascertaining alpha-2 adrenoceptor antagonism in the central nervous system--namely, accumulation of cortical dopa and antagonism of mydriasis induced by the alpha-2 agonist, clonidine--L-659,066 had, respectively, less than 1/345th and about 1/5000th of the potency of L-657,743. In mice, L-659,066 had, respectively, approximately 1/29th and 1/1400th of the potency of L-657,743 as an antagonist in vivo of the predominately peripherally mediated inhibition of colonic propulsion caused by clonidine as compared with the mainly centrally mediated antinocisponsive action elicited by the alpha-2 agonist UK 14,304. The foregoing findings are consistent with poor penetration of the blood-brain barrier by L-659,066.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896241 TI - Stereospecificity of beta adrenergic antagonists: R-enantiomers show increased selectivity for beta-2 receptors in ciliary process. AB - The (+)-stereoisomers of arylethanolamine beta adrenergic agonists and antagonists are usually much less active in biological systems than their corresponding (-)-forms. In the eye, however, prior physiological studies have shown that these (+)-stereoisomers are unexpectedly potent in altering intraocular pressure, results which could be due to a difference in distribution and metabolism or to a difference in receptor interaction. The present experiments evaluated six stereoisomeric pairs of beta adrenergic antagonists for their ability to block rabbit ciliary process and cardiac beta adrenergic receptors activating adenylate cyclase, in vitro, under conditions in which the effects of drug metabolism, distribution and membrane lipid solubility were minimized. In the heart, all six pairs of antagonists demonstrated the expected increased potency of (-)-forms, with isomeric activity ratios of: 33 for metoprolol, 44 for timolol; 48 for bunitrolol; 76 for t-butyl-betaxolol; 100 for t-butyl-didesmethyl-ICI-118,551; and 530 for betaxolol. Under identical assay conditions in the ciliary process, (+)-enantiomers were much more potent relative to (-)-forms, with isomeric activity ratios of: 0.82 for timolol; 3.3 for bunitrolol; 7.4 for t-butyl-didesmethyl-ICI-118,551; 10 for metoprolol; 16 for t butyl-betaxolol; and 190 for betaxolol. With the exception of metoprolol, all (+) enantiomers demonstrated a substantially higher absolute affinity for ciliary process receptors (known to be almost exclusively of the beta-2 subtype) than for cardiac receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896242 TI - Single appointment intraoral repair of a broken solder joint. PMID- 2896243 TI - Absent taeniae coli in multiple endocrine neoplasia type III. PMID- 2896244 TI - Androgenic control of immunoreactive somatostatin in the Harderian gland of the Syrian hamster. AB - Harderian glands of Syrian hamsters contained measurable levels of immunoreactive somatostatin. After an extraction procedure, serial dilutions of tissue were assayed and showed parallelism in the displacement curve with dilutions of purified somatostatin standard in the radioimmunoassay. Somatostatin concentrations were higher in female hamsters (10.0 +/- 2.1 ng/mg protein) than in males (2.6 +/- 0.4 ng/mg protein). Castrated males had somatostatin values in the range of females (12.4 +/- 2.3 ng/mg protein) at 1 month after gonadectomy. Testosterone implants prevented the rise of Harderian gland somatostatin in castrated males. Gonadectomized males had lower somatostatin content in the gland than did control males (1.0 +/- 0.2 ng/mg protein) at 2 months after castration. Somatostatin values in females were unaffected by gonadectomy, but there were variations during the oestrous cycle, with a nadir detected at dioestrus-1 and maximal values coincident with the day of the ovulation. PMID- 2896245 TI - 2,4-Diamino-6,7-dimethoxyquinoline derivatives as alpha 1-adrenoceptor antagonists and antihypertensive agents. AB - A series of 2,4-diamino-6,7-dimethoxyquinoline derivatives (2), prepared by LDA- or ZnCl2-mediated intramolecular cyclization of an N-[1-(dialkylamino)ethylidene] 2-cyano-4,5-dimethoxyaniline (3), was evaluated for alpha-adrenoceptor affinity and antihypertensive activity. Most compounds displayed high in vitro binding affinities (Ki's, 10(-10) M) for alpha 1-adrenoceptors with alpha 1-/alpha 2 selectivity ratios of at least 10,000. 4-Amino-2-[4-(2-furoyl)piperazin-1-yl]-6,7 dimethoxyquinoline++ + (14) proved to be the most potent member (Ki = 1.4 X 10( 10) M) of series 2, and displayed no activity at alpha 2-adrenoceptor binding sites at concentrations up to 10(-6) M. In the rabbit pulmonary artery, 14 was a highly potent (pA2 = 9.76 +/- 0.26) competitive antagonist of the alpha 1 mediated vasoconstrictor action of noradrenaline and was some 20 times more active than prazosin. pKa measurements confirmed that, at physiological pH, N-1 protonation of series 2 would efficiently provide 1b, a key pharmacophore for alpha 1-adrenoceptor recognition. Antihypertensive activity for series 2 was evaluated after oral administration (3 mg/kg) to spontaneously hypertensive rats (SHR) and falls in blood pressure were determined at 1 and 4.5 h. Various quinoline derivatives (2) proved to be effective antihypertensive agents in SHR, with both efficacy and duration of action at least equivalent to prazosin, and 14 displayed the most favorable overall profile. These observations are consistent with the high affinity and selectivity displayed by series 2 for postjunctional alpha 1-adrenoceptors. PMID- 2896246 TI - 1,3-Diamino-6,7-dimethoxyisoquinoline derivatives as potential alpha 1 adrenoceptor antagonists. AB - Treatment of 2-methyl-4,5-dimethoxybenzonitrile (3) with LDA followed by reaction with an N,N-disubstituted cyanamide provided a series of 1,3-diamino-6,7 dimethoxyisoquinolines (2), which were evaluated for alpha-adrenoceptor binding affinity and antihypertensive activity. 1-Amino-3-(dimethylamino)-6,7 dimethoxyisoquinoline (4) showed no significant affinity (Ki much greater than 10(-6) M) for alpha 1-adrenoceptors, while the corresponding 3-(2-furoylpiperazin 1-yl) analogue (8; Ki = 1.6 X 10(-7) M) was some 1000-fold less potent than prazosin. pKa data showed that N-2 protonation (34%) of 4 (pKa = 7.1) would occur at physiological pH, in agreement with X-ray crystallographic analysis of 8.HCl. Comparison of positive charge distribution following protonation of 4 with the corresponding quinoline and quinazoline cations confirmed N-1 protonation is required for these heterocyclic nuclei to bind efficiently to the alpha 1 adrenoceptor. Computer-assisted comparison of the X-ray structures of 8 and prazosin suggested that the 4.0 kcal/mol difference in alpha 1-adrenoceptor binding energies was largely due to salt-bridge formation (ca. 3.0 kcal/mol) between the protonated quinazoline and the receptor protein. None of the isoquinolines (2) proved to be effective antihypertensive agents in rats even when administered at relatively high doses (10 mg/kg). These results support the hypothesis that the antihypertensive activity of prazosin, doxazosin, and related derivatives derives solely from alpha 1-adrenoceptor blockade. PMID- 2896248 TI - The use of testicular volume as a clinical marker for cytogenetic disorders in mentally retarded males. AB - The testicular volumes (V) of 817 adult (non-Down's syndrome) institutionalized males were calculated. The mean testicular volume was 19.5 +/- 15.8 ml, comparable to the normal adult male mean of 17-19 ml. However, the number of institutionalized males with V greater than or equal to 25 ml and V less than or equal to 10 ml was increased approximately fourfold over the normal male population. Resident adult males were grouped into three categories based on their testicular volumes: (1) V greater than or equal to 25 ml (macro-orchid); (2) V less than or equal to 15 ml (micro-orchid); and (3) 15 less than V less than 25 ml ('normal'). An equal number of randomly selected males from each category were cytogenetically screened for the fra(X) syndrome as well as for non fra(X) chromosome abnormalities. The overall frequencies of these disorders were 3.1% and 3.9%, respectively. The fra(X) syndrome was found in a significantly higher percentage of macro-orchid males (10.3%) as compared to males with either micro-orchidism (1.2%) or normal testicular volume (1.2%). There was no significant difference in the distribution of either fra(X) negative non-specific XLMR or non-fra(X) chromosome abnormalities among resident males from these three categories. Testicular volumes greater than or equal to 25 ml, especially those exceeding 40 ml, were thus shown to be useful clinical markers in the diagnosis of the fra(X) syndrome. Reduced testicular volume was not a useful clinical marker in the evaluation of other non-Down's syndrome chromosome abnormalities. PMID- 2896247 TI - Indoline analogues of idazoxan: potent alpha 2-antagonists and alpha 1-agonists. AB - The synthesis and alpha-adrenergic activity of a series of substituted 2 imidazolinylindolines are described. Substitution in the indoline ring generated compounds with a spectrum of adrenoceptor antagonist/agonist profiles that proved sensitive to both the nature and position of the substituent. Many of the derivatives possess greater presynaptic antagonist potency than the corresponding benzodioxan 1, dihydrobenzofuran 2, and indan 3 analogues; however, this alpha 2 antagonism is often accompanied by alpha 1-agonist activity. It was not possible to separate alpha 2-antagonist from alpha 1-agonist properties in this series. Compounds of most interest proved to be the N-ethyl 6, 5-chloro-N-methyl 18, and 5-chloro-N-ethyl 23 derivatives, all being potent alpha 2-antagonists and alpha 1 agonists. Substitution at the 4- and 7-position of the indoline ring generally gave compounds with nonselective agonist properties. PMID- 2896250 TI - Cardiovascular aspects of pharmacology of berberine: I. Alpha-adrenoceptor blocking action of berberine in isolated rat anococcygeus muscle and rabbit aortic strip. PMID- 2896251 TI - Thin layer chromatographic assay for prizidilol in serum. PMID- 2896249 TI - Blocking action of berberine on alpha 2- and alpha 1-adrenoceptors in rat vas deferens and anococcygeus muscle. PMID- 2896252 TI - This month in investigative urology. Laser lithotripsy. PMID- 2896253 TI - Laser induced shock wave lithotripsy--biologic effects of nanosecond pulses. AB - Laser energy of a Nd-YAG laser (1064 nm. wave length, 8 nsec pulse duration) was directed against various tissue cultures and the urothelium of the ureter, bladder and kidney parenchyma in pigs. Single pulse energy was 50 to 120 mJ with a repetition rate of 20 Hz. Urothelium and kidney parenchyma were irradiated in seven pigs. Tissue samples were examined histologically and electron microscopically directly, two, four, eight and 12 days after irradiation. No macroscopic lesion could be found. Maximum energy caused a small 'rupture cone' of 40 micron. depth. No thermic effects or necrosis resulted, so that no harm is to be expected with unintentional irradiation during laser stone disintegration. PMID- 2896254 TI - P-fimbriae receptors in patients with chronic pyelonephritis. AB - The adherence of fluorescein isothiocyanate-labeled P-fimbriated Escherichia coli to uroepithelial cells from 19 women with chronic pyelonephritis was determined with the fluorescence-activated cell sorting technique. The application of this method has made it possible to study bacterial binding to a large number of cells. Renal function was determined in all patients and the recurrences of P fimbriated Escherichia coli bacteriuria, cystitis and acute pyelonephritis during a 3-year followup were studied. We found a significant correlation between the P fimbriae receptor accessibility on uroepithelial cells and glomerular filtration rate (r equals -0.75, p less than 0.001). Uroepithelial cells from the patients with chronic pyelonephritis and renal insufficiency had a higher binding capacity of P-fimbriated Escherichia coli than uroepithelial cells from patients with a normal glomerular filtration rate. There was no correlation between kidney function and the availability of P-fimbriae receptors in a control group of patients with polycystic kidney disease. PMID- 2896255 TI - The partial agonist activity of xamoterol (ICI 118,587) studied by heart rate response in pithed rats. AB - The partial agonist activity of xamoterol was evaluated by measuring changes in heart rate (HR) in pithed rats. Xamoterol showed dose-dependent positive chronotropic effects in catecholamine-depleted pithed rats (HR: 199 +/- 6 beats/min) and dose-dependent negative chronotropic effects in sympathetic nerve stimulated pithed rats (HR: 325 +/- 16 beats/min). In contrast, isoproterenol exerted dose-dependent positive chronotropic effects in either condition (HR: 189 +/- 7 and 332 +/- 5 beats/min) and propranolol exerted dose-dependent negative chronotropic effects in either condition (HR: 209 +/- 5 and 344 +/- 19 beats/min). When exogenous noradrenaline was continuously infused into catecholamine-depleted pithed rats, xamoterol showed dose-related positive chronotropic effects with noradrenaline at 0.5 micrograms/(kg min) (HR: 235 +/- 4 beats/min), virtually no effects at 1.5 micrograms/(kg min) (HR: 297 +/- 11 beats/min) and dose-related negative chronotropic effects at 5 micrograms/(kg min) (HR: 330 +/- 5 beats/min). During continuous infusion of xamoterol [100 ng/(kg min)] into pithed rats, the control HR before stimulation was increased and the maximum increase produced by the sympathetic nerve stimuli at 0.25 to 4 Hz decreased. The maximum increase in HR brought about by xamoterol was about 71% of that induced by isoproterenol, and those by pindolol and practolol were about 40% and 21% respectively. It is concluded that xamoterol is a partial agonist with a strong agonist action. PMID- 2896256 TI - Effect of xamoterol on myocardial energetics in man. AB - We analyzed the effect of xamoterol (beta 1-partial agonist) on myocardial energetics in 8 patients with normal left ventricular function. We measured resting systemic and coronary hemodynamics before and after a single intravenous injection of xamoterol (0.1 mg/kg). This agent increased heart rate from 70 +/- 7 to 80 +/- 11 beats/min (p less than 0.05) and cardiac index from 2.9 +/- 0.5 to 3.2 +/- 0.5 L/min.m2 (p less than 0.01), respectively. Left ventricular peak positive dp/dt (1870 +/- 350 vs 2620 +/- 580 mmHg/sec (p less than 0.01) and left ventricular ejection fraction (62 +/- 7 vs 70 +/- 7% (p less than 0.01] also increased, while left ventricular end-diastolic pressure (9 +/- 3 vs 5 +/- 3 mmHg (p less than 0.01] and volume index (70 +/- 14 vs 58 +/- 16 ml/m2 (p less than 0.01] decreased. Coronary blood flow and total myocardial oxygen consumption did not change significantly after intervention. As a result, xamoterol enhanced left ventricular external mechanical work versus myocardial oxygen consumption ratio (mechanical efficiency) from 20 +/- 4 to 24 +/- 5% (p less than 0.01). Myocardial oxygen extraction ratio decreased significantly (p less than 0.01) from 66 +/- 5 to 62 +/- 5% after xamoterol. We conclude that xamoterol augments left ventricular mechanical efficiency accompanied by a decrease in coronary vascular tone in patients with normal cardiac function. PMID- 2896257 TI - Role of alpha 1-adrenergic receptors and the effect of bunazosin on the histopathology of cardiomyopathic Syrian hamsters of strain BIO 14.6. AB - In order to clarify the pathological involvement of the sympathetic nervous system in the development of cardiomyopathy, a receptor-binding study was carried out on cardiomyopathic Syrian hamsters of strain BIO 14.6 (BIO) at 21 days (prenecrotic stage); 35-42 days (onset of cardiomyopathy); and 70-84 days of life (early cardiac hypertrophy). The newly developed alpha 1-blocker (bunazosin hydrochloride) was initially administered at doses of 100 micrograms/kg or 10 mg/kg to BIO hamsters at 21 days of life and continued for 70 days. At the onset of cardiomyopathy and early cardiac hypertrophy, there was an increase in the number of alpha 1-receptors in the BIO hamsters compared to controls, but there were no significant changes at the prenecrotic stage. On histopathological examination, 10 mg/kg bunazosin had a significant beneficial effect on cardiomyopathy [area of necrosis 1.38% in untreated vs 0.33% in treated animals; area of calcification 2.70% (untreated) vs 0.60% (treated); area of all myocardial injuries 6.97% (untreated) vs 3.19% (treated)]. However, 100 micrograms/kg bunazosin had no effect. It was concluded that the increase in the number of alpha 1-receptors may not be involved in the pathogenesis of cardiomyopathy but that alpha 1-receptors could be implicated in the later progression of the condition. PMID- 2896258 TI - [Infection defense antigens against pathogenic viruses to human. Infection defense antigens and genetic code--trend and progress of study on biomolecular analysis. n. Gene structure of HTLV and infection defense antigens]. PMID- 2896259 TI - [Trends in research in developing new type of vaccines--aiming at efficacy and safety. HTLV vaccine]. PMID- 2896260 TI - Biological and therapeutic aspects of proliferative vitreoretinopathy. AB - Conventional vitreoretinal surgery for proliferative vitreoretinopathy is unsatisfactory despite numerous innovations over the past 20 years. Silicone oil injections in this series resulted in 70% reattachment of these end-stage cases, but within twelve months over 90% had no useful visual result. The development of an in vitro model for 3-dimensional culture of cells has allowed evaluation of numerous potential drugs with anti-proliferative or anti-contractile activities. Amongst these, taxol has shown the most promise. There remain, however, doubts about possible long-term toxicity to the optic nerve and retina. It is concluded that a more physiological vitreous substitute and more specific anti proliferative or anti-contractile pharmacological agents are needed. PMID- 2896261 TI - Phagocytosis of piliated and non-piliated Corynebacterium renale by murine polymorphonuclear leukocytes. PMID- 2896263 TI - Detection of pilus antigen Att25 (FY) on Escherichia coli from porcine colibacillosis. PMID- 2896262 TI - Spermatogenic function in cryptorchid dogs after orchiopexy. PMID- 2896264 TI - Ontogeny of gastroenteropancreatic (GEP) endocrine cells in mouse and porcine embryos. PMID- 2896265 TI - Reversal of somatostatin inhibition of AVP-induced cAMP by pertussis toxin. AB - The effect of somatostatin on the stimulation of adenosine-3',5'-cyclic monophosphate (cAMP) production by arginine vasopressin (AVP) was examined in rat renal papillary collecting tubule cells in culture. The presence of phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine AVP at a concentration of 1 X 10(-10) M or higher significantly increased cellular cAMP levels in a dose dependent manner. The stimulation by AVP of cellular cAMP production was significantly attenuated by 1 X 10(-6) M somatostatin (1 X 10(-9) M AVP, 477.5 +/ 23.0 vs. 292.4 +/- 28.5 fmol/micrograms protein per 10 min, P less than 0.01). When the cells were pretreated with pertussis toxin, pertussis toxin completely abolished the inhibitory effect of somatostatin on cellular cAMP production in response to AVP. Such an effect was obtained with a concentration of 0.1 ng/ml or higher of pertussis toxin and an incubation time of longer than an hour. The exposure of cells to 100 ng/ml pertussis toxin for two hours recovered the cellular cAMP response to 1 X 10(-9) M AVP in the presence of 1 X 10(-6) M somatostatin, the value of which 527.1 +/- 32.6 fmol/micrograms protein per 10 minutes, was a comparable level to that in response to only 1 X 10(-9) M AVP. Also, somatostatin inhibited the cellular cAMP response to glucagon and cholera toxin, but did not inhibit basal and forskolin-stimulated cAMP levels. Pertussis toxin treatment of cells completely abolished these inhibitory effects of somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896267 TI - Effect of beta-blocker administration in the post-valvotomy management of infants with pulmonary atresia and intact ventricular septum. PMID- 2896266 TI - [Comparative multicenter study of carteolol eyedrops with other beta blockers in 768 patients under normal conditions]. AB - In an open multi-center study involving 768 patients the efficacy and tolerability of Carteolol eye drops as compared to other beta blockers were investigated. The patients started to use the new medication without a prior washout period. In patients who were well stabilized (57%), IOP either did not change when the medication was switched to Carteolol (73%) or it actually decreased. In 78% of the patients who had not responded altogether satisfactorily to the pretreatment, Carteolol eye drops lowered IOP to a tolerable level of 21 mm Hg or less without using any comedication. IOP remained hypertonic under Carteolol in only 19% of the cases. Fewer systemic and local side effects were observed under Carteolol therapy. Patients had fewer problems going upstairs. Burning after installation decreased by 25% to 2%. Even fluorescein-positive corneal findings almost completely disappeared under Carteolol. PMID- 2896268 TI - [Experience with the treatment of acute renal failure in patients with hemorrhagic fever with nephrotic syndrome]. PMID- 2896270 TI - [The international congress of the movement "World physicians in the prevention of nuclear warfare"]. PMID- 2896269 TI - [Use of adrenergic beta receptor blockaders in gastroenterology]. PMID- 2896271 TI - [Effect of prolonged inhalation of acetic acid vapors on several human functional parameters]. AB - Test subjects were continuously exposed to acetic acid vapors which form a constant component of enclosed atmospheres. The inhalation time was 15 to 22 days at concentrations of 5, 10 and 15 mg/m3 or 10 days at a concentration of 26 mg/m3. Physiological parameters showed statistically significant changes at concentrations of 15 and 26 mg/m3. It is suggested that the changes are not adaptive but have been produced by the adverse effect of acetic acid vapors on the human body. It is therefore concluded that the 15 mg/m3 concentration is threshold and the 5 and 10 mg/m3 concentrations are ineffective in terms of the tests used. The most sensitive method is measurement of hydrocarbons (C2-C5), especially ethylene, in the exhaled air. PMID- 2896272 TI - [Cardiac rhythms of animals drinking reclaimed water with various sodium and potassium ion concentrations]. AB - The effect of reclaimed potable water on cardiac rhythms of 190 noninbred white male rats was investigated in a 6-month experiment. The water contained 25.0 to 100.0 mg/l sodium and/or 2.5 to 10.0 mg/l potassium. The water containing 100 mg/l sodium and 10 mg/l potassium caused changes in both compartments of the autonomic nervous system controlling cardiac rhythms. The water containing 75.0 and 50.0 mg/l sodium and 7.5 and 5.0 mg/l potassium produced insignificant changes in cardiac rhythms. The water containing lower concentrations of sodium (25.0 mg/l) and potassium (2.5 mg/l) had no effect. PMID- 2896273 TI - [Setting a maximum allowable concentration for urea in reclaimed potable water and evaluating the nature of its biological action]. AB - The purpose of the study was to identify maxim allowable concentrations of urea in reclaimed potable water. The urea concentration equal to 80 mg/l is the threshold dose influencing the taste and flavor of water. Urea is a low toxicity substance (LD50 = 14,300 mg/kg), the effect of which is not cumulative. However, when used in high doses it affects bioenergetic and cholinergic processes and causes changes in ECG, higher nervous activity and visceral structure. It has been shown that when applied to warm-blooded animals the acting dose of urea is 14.3 and 1.43 mg/kg (1/1000 and 1/10000 LD50), the threshold dose is 0.72 mg/kg (1/20000 LD50), and the ineffective dose is 0.36 mg/kg (1/40000 LD50) which amounts to the concentration of 10 mg/l. In terms of toxic effects the dose equal to 10 mg/l is taken to be the maximally allowable concentration of urea. It is recommended to use the Laham biotest for measuring urea in water. PMID- 2896274 TI - The conundrum of the effect of beta-blockade on myocardial oxygen consumption. AB - The effect of propranolol on myocardial oxygen consumption was studied in in situ canine hearts. In 12 afterload independent isovolumic hearts propranolol increased MVO2 an average of 19 +/- 3% (P less than 0.01) for all peaked developed pressure intervals from 75 to 175 mm Hg, secondary to increased wall stress. In 10 hearts instrumented for computer acquisition of pressure-volume workloops during progressive volume loading on right heart bypass, propranolol decreased preload recruitable stroke work an average of 36% (P less than 0.05). However, propranolol failed to decrease the amount of oxygen consumed for basal metabolism or external mechanical work when MVO2 is indexed for heart rate, heart weight, and stroke work. Therefore, propranolol does not decrease MVO2 for individual contractions and does not affect the energy requirements for basal metabolism, excitation-contraction coupling, and heat generation, in contrast to results obtained with beta agonists. PMID- 2896275 TI - Dexamethasone administration induces increased glutaminase specific activity in the jejunum and colon. AB - Exogenous glucocorticoids markedly increase the in vivo uptake and utilization of glutamine by the intestine. Since glutamine is the major oxidative fuel for the small intestine, we investigated whether glucocorticoids induce changes in the specific activity of the enzymes that mediate glutamine degradation (glutaminase) and synthesis (glutamine synthetase). Male Sprague-Dawley rats received a 7-day elemental diet. On Day 5, animals were randomized to one of four groups and received either saline (Control) or one of three doses of dexamethasone im: 0.1 mg/kg (Lodex); 0.3 mg/kg (Middex); or 0.6 mg/kg (Hidex). Forty-eight hours later jejunal and colonic segments were assayed for protein, glutaminase, and glutamine synthetase activity. A stress dose of dexamethasone (Hidex) produced a significant increase in both jejunal and colonic glutaminase specific activity (P less than 0.02 vs Control and P less than 0.05 vs Control, respectively). These data suggest a mechanism whereby glucocorticoids increase the intestinal utilization of glutamine by increasing the specific activity of intestinal glutaminase. PMID- 2896276 TI - Simultaneous assessment of membrane-stabilizing and beta-adrenoceptor blocking activity of drugs with the rat isolated left atria. AB - Three consecutive challenges of the rat isolated left atria with electrical stimulation and then electrical stimulation and isoprenaline were made. The responses to electrical stimulation decreased and the responses to isoprenaline increased with consecutive challenges such that the maximal combined response to electrical stimulation and isoprenaline remained constant. The sensitivity (pD2) to isoprenaline decreased with successive challenges. Thus, in studies of the effects of drugs on the responses to electrical stimulation and isoprenaline, it is necessary to perform parallel experiments with untreated atria to monitor changes in the responses unrelated to the addition of drug. Analysis of the effects of procaine, metoprolol, and propranolol on the responses to electrical stimulation and/or isoprenaline demonstrated distinct contractile manifestations of beta-adrenoceptor blocking and membrane stabilizing activity. The beta adrenoceptor blocking activity of metroprolol at 10(-7) M and propranolol (3 X 10(-9)-10(-6) M) consisted of parallel rightward shifts of the concentration response curves to isoprenaline alone. There were three components to the membrane-stabilizing action of drugs: first, there was a decrease in the responses to electrical stimulation alone, which was observed with procaine at greater than or equal to 10(-4) M and propranolol at greater than or equal to 3 X 10(-9) M, second, there was a small parallel rightward shift of concentration response curve to isoprenaline alone with metoprolol at 10(-6) M and propranolol at 3 X 10(-6) M (that the inhibitory effects of metoprolol at 10(-6) M or propranolol at 3 X 10(-6) M are greater than can be explained by beta adrenoceptor blockade only may be detected either by determining pA2 values from the formula pA2 = pAx + log(x - 1) or by Schild analysis); third, the highest concentrations of procaine (3 X 10(-4) M) and propranolol (10(-5) M) tested decreased the maximal combined response to electrical stimulation and isoprenaline. PMID- 2896277 TI - Biosynthesis and storage of gonadoliberin and somatostatin. PMID- 2896278 TI - The role of the pineal gland in neurohumoral regulation. PMID- 2896279 TI - Adrenergic transmission and the neurohypophyseal hormones under different conditions of water metabolism. PMID- 2896280 TI - The regulation of gonadotropin release from the anterior pituitary. PMID- 2896282 TI - [I-131-meta-iodobenzylguanidine and multiple endocrine adenomatosis type II]. PMID- 2896281 TI - Porphyrins and gamma-glutamyltranspeptidase activity in transplantable clear-cell renal carcinoma induced with aflatoxin B1 in rats. PMID- 2896283 TI - [Unusual complications in a case of Mediterranean boutonneuse fever]. PMID- 2896284 TI - [Glafenine hepatotoxicity]. PMID- 2896285 TI - Evidence for a direct and indirect action of leucine enkephalin at the feline ileocecal sphincter. AB - An in vitro whole organ bath preparation was used to examine the effects of leucine enkephalin on the cat ileocecal sphincter (ICS) intraluminal pressure and myoelectric activity. The bath allowed separation of the bathing media surrounding the ICS and the ileum. Leucine enkephalin (2 x 10(-7) M) when added to the ileal bathing medium caused a delayed increase in ICS spike activity and pressure which was blocked by tetrodotoxin (10(-5)M). In contrast, leucine enkephalin (2 x 10(-7)M) added directly to the ICS bathing medium caused an immediate spike-associated contractile response which was tetrodotoxin-resistant. Thus both an indirect and direct opiate action at the ICS was demonstrated. PMID- 2896286 TI - The benzodiazepine receptor inverse agonists beta-CCM and RO 15-3505 both reverse the anxiolytic effects of ethanol in mice. AB - The antagonistic effects of the benzodiazepine receptor inverse agonist beta-CCM (1 mg/kg) and of the partial inverse agonist RO 15-3505 (3 mg/kg) on the anxiolytic properties of ethanol (1 g/kg) in mice confronted with a light/dark choice procedure and with the staircase test were investigated. Both drugs reversed the effects of ethanol on some of the behavioral parameters, but beta CCM alone elicited anxiogenic intrinsic effects. RO 15-3505 induced seizures in mice treated with a subconvulsant dose of pentylenetetrazole, the most efficient doses being 3 and 6 mg/kg. These data indicate that beta-CCM and RO 15-3505 can reverse some of the anxiolytic effects of ethanol, acting probably to oppose GABA function via the benzodiazepine receptor. PMID- 2896288 TI - The use of DNA probes identifying restriction-fragment-length polymorphisms to examine the Mycobacterium avium complex. AB - DNA probes were used to identify restriction-fragment-length polymorphisms (RFLPs) in DNA samples, demonstrating that the Mycobacterium avium complex could be clearly divided into M. avium and Mycobacterium intracellulare strains. Less than 2% DNA base substitution was found between M. avium strains, whereas the M. intracellulare strains had greater than 15% base substitution. The Johne's disease bacillus, Mycobacterium paratuberculosis (American type strain), was found to be distinguishable from the M. avium complex serotypes examined. Strain 18 was found to be identical to M. avium. The rat leprosy bacillus, Mycobacterium lepraemurium, was found to be very closely related, but not identical, to M. avium. PMID- 2896287 TI - The neurosecretory effect of ouabain on isolated rabbit ileal mucosa. AB - Ouabain, when added to fluid bathing rabbit ileal mucosa mounted in a flux chamber, transiently increases short circuit current, implying a paradoxical secretory response. To determine the cause of this change, we studied unidirectional fluxes of 36Cl and 23Na and the effects of ion substitution, of reduced Ca concentration, verapamil, tetrodotoxin and atropine. Ouabain 0.1 mM, transiently increased the serosal to mucosal flux of Cl and Na, increased Isc and PD and reduced ion conductance. The Isc response to ouabain was diminished by reducing the bath fluid concentration of Cl, of Ca, and by adding verapamil. Tetrodotoxin both delayed and reduced the maximal Isc response; atropine had no effect. We conclude that ouabain acts by releasing a neurotransmitter of unknown identity and by increasing the serosal to mucosal flux of Cl. PMID- 2896289 TI - Evolutionary relationships in the genus Bordetella. AB - The nucleotide sequence of the pertussis toxin operon of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica, has shown that the last two species contain many common mutations and are likely to derive from a common ancestor (Arico and Rappuoli, 1987). To elucidate further the evolutionary relationships between the Bordetella species, we have cloned and sequenced the promoter region and the gene coding for the S1 subunit of pertussis toxin from additional B. pertussis strains, such as the type strain BP 18323 and two recent clinical isolates, namely strain BP 13456 from Sweden and strain BP SA1 from Italy. While the strains BP SA1 and BP 13456 are shown to differ from the published B. pertussis sequences by only one base pair, the type strain BP 18323 contains a total of 11 base-pair substitutions. Remarkably, 9 of the 11 substitutions found in BP 18323 are also common to B. parapertussis and B. bronchiseptica, strongly suggesting that this strain derives from the same ancestor as B. parapertussis and B. bronchiseptica. Computer analysis of the sequence data allows the construction of an evolutionary 'tree' showing that the B. pertussis strains are very homogeneous and significantly distant from B. parapertussis and B. bronchiseptica. Therefore the proposed conversion from B. parapertussis to B. pertussis appears highly improbable. PMID- 2896290 TI - The frequency of expression of pyelonephritis-associated pili is under regulatory control. AB - The Escherichia coli urinary tract isolate C1212 contains two pyelonephritis associated pili (pap) DNA sequences designated here as pap-17 and pap-21. Each of these pap sequences encodes antigenically-distinct pilin monomers, pilin-17 and pilin-21, respectively. Most individual strain C1212 cells isolated from a single bacterial colony expressed pilin-21. Only a small fraction (5%) of strain C1212 cells expressed pilin-17. Most of the latter population simultaneously expressed pilin-21, but a low percentage of cells expressed pili composed of pilin-17 alone. In contrast, almost every E. coli K-12 cell containing multicopy pap-17 expressed pilin-17 at the cell surface. These results indicated that the regulation of pilin-17 expression observed for strain C1212 was lost when pap-17 was in the multicopy state. Transfer of pap-17 to a single copy vector resulted in a pilin-17 expression frequency lower than strain C1212 (1%). Using E. coli K 12 containing single copy pap-17, we found that the frequency of pilin-17 expression increased about 15-fold when pap-21 was present in multiple copies in trans. Subcloning of pap-21 showed that a 2.2 kilobase-pair DNA sequence adjacent to, but not including, the pilin-21 structural gene was sufficient for activation of pilin-17 expression. PMID- 2896291 TI - Molecular characterization of the resolvase gene, res, carried by a multicopy plasmid from Clostridium perfringens: common evolutionary origin for prokaryotic site-specific recombinases. AB - Clostridium perfringens strain CPN50 harbours a 10.2 kb plasmid known as pIP404 which, in addition to a set of UV-inducible genes involved in bacteriocin production, carries res, a gene probably encoding a site-specific recombinase. The RES protein is highly homologous to the resolvases of transposons from both Gram-negative and Gram-positive bacteria as well as enzymes involved in site specific DNA inversion. A likely role for the RES protein would be to stabilize pIP404 by reducing the number of plasmid multimers resulting from homologous recombination. A putative resolution site for RES action was found overlapping the res promoter. Phylogenetic analysis of the primary structures of ten site specific recombinases suggested a common descent and showed the RES protein to be closest to the resolvase encoded by Tn917 from Streptococcus faecalis. PMID- 2896292 TI - Expression of multiple types of N-methyl Phe pili in Pseudomonas aeruginosa. AB - The nature of pili synthesized by Pseudomonas aeruginosa when plasmid-borne genes of homologous pilins from Bacteroides nodosus are introduced as thermoregulated expression systems has been ascertained. Expression of B. nodosus pili inhibited the production of indigenous P. aeruginosa pili, and an organism harbouring pilin genes from two strains of B. nodosus produced two serologically distinct populations of pili on each cell. Simultaneous production of both indigenous and foreign pili was achieved by partial induction of expression. Homogeneity in pilus structure suggests either that there is an exclusive specificity of interaction between identical pilin subunits in pilus assembly, or that each pilus is produced from the translation products of a single messenger RNA molecule, with translation and pilus assembly closely coupled. PMID- 2896293 TI - [Italian Society of Dentistry and Maxillofacial Surgery (founded in Turin, 6 June 1957)]. PMID- 2896294 TI - Mucosal nerves and immunological function. PMID- 2896295 TI - Agglutination of E. coli by secretory IgA--a result of interaction between bacterial mannose-specific adhesins and immunoglobulin carbohydrate? PMID- 2896296 TI - Binding of bacteria to mucosal surfaces. PMID- 2896297 TI - Human lymphokine-activated killer cells: further isolation and characterization of the precursor and effector cell. AB - In a series of experiments we have demonstrated the progressive enrichment (5- to 40-fold) in lymphokine-activated killer (LAK) precursor activity by adherence depletion, sheep red cell rosetting, and depletion of CD3- and DR-positive lymphocytes. The LAK precursor cell thus appears to fall within the 'null' cell population. CD16 and CD11 are cell surface antigens expressed on the surface of the LAK precursor as demonstrated in sorting experiments. A 6- to 100-fold enrichment compared to unseparated peripheral blood was noted when sorted cells positive for CD16 and CD11 were tested. The LAK effector has been identified as being primarily CD3- and CD2+. Similar sorting equipment demonstrated a 7- to 500 fold difference in lytic activity for fresh tumor when comparing CD2+/CD3- and CD2+/CD3+ cells. The CD16+/CD11+ lymphocyte can proliferate in response to interleukin-2 (IL-2) alone in the absence of accessory cells and can be expanded in IL-2 alone with maintenance of lytic activity. PMID- 2896298 TI - Immunomodulating effects in vitro of interleukin-2 and interferon-gamma on human blood and bone marrow mononuclear cells. AB - Mononuclear cells (MNC) derived from peripheral blood (PBMNC) of 23 normal donors and 4 AIDS patients, and from bone marrow (BMMNC) of 15 normal donors were incubated at 37 degrees C in culture medium alone or in the presence of either natural or recombinant human interleukin-2 (IL-2) or recombinant human interferon gamma (IFN-gamma; 1-1,000 U/ml). The cultured cells were washed on days 1, 4 or 7 and tested for various immune functions in vitro and for cell surface phenotype. IL-2, but not IFN-gamma, was found mitogenic for both PBMNC and BMMNC. The natural killer (NK) activity of both PBMNC and BMMNC was the only function tested that was markedly augmented (over 100-fold compared to medium control) by both lymphokines. Pretreatment of PBMNC with IL-2 at greater than or equal to 10 U/ml profoundly suppressed (up to 90%) various functions, such as mitogenic responses (phytohemmagglutinin, concanavalin A, pokeweed mitogen), allogeneic mixed leukocyte reaction, antibody production and T cell colony formation in agar. In contrast, some BMMNC functions were elevated at low doses of IL-2 and IFN-gamma, and significant suppression of BMMNC was seen only with high doses of IL-2 (greater than or equal to 100 U/ml) and IFN-gamma (1,000 U/ml). IL-2 was by far more effective than IFN-gamma in both the amplification of NK activity and the suppression of most of the other functions. IL-2, but not IFN-gamma, was found to activate/induce suppressor cells and increased the proportion of Leu-2+ (CD8) cells in PBMNC; the suppressive effect was time- and dose-dependent. The IL-2 induced suppression could be diminished by inclusion of anti-IL-2 antibody during the pretreatment phase. Similar suppressive effects were noted in PBMNC from AIDS patients. These findings suggest that: (a) high-dose IL-2 may elicit immunosuppression which can be mediated by nondiscriminative highly cytotoxic cells (i.e. lymphokine-activated killer cells) and/or by noncytotoxic, nonspecific suppressor cells, and (b) that PBMNC respond differently to the lymphokines than do BMMNC. PMID- 2896299 TI - Chromosome aberrations associated with CAD gene amplification in Chinese hamster cultured cells. AB - Eleven sublines with increasing resistance to N-phosphonacetyl-L-aspartate (PALA) were isolated from the V79,B7 Chinese hamster cell line. Aspartate transcarbamylase activity and CAD gene copy number increased with increasing resistance of sublines. In situ hybridization with a DNA probe for the CAD gene showed that the amplified sequences resided in the terminal region of a marker chromosome with elongated q arms. This region stained homogeneously after G banding. A high incidence of both numerical and structural chromosome aberrations was found in PALA-resistant cells. In hyperdiploid and polyploid cells, containing 2 copies of the marker chromosome, dicentrics were found at a very high frequency. As indicated by in situ hybridization and G-banding, they originated from a rearrangement involving 2 homologous marker chromosomes. PMID- 2896301 TI - Another retroviral disease of the nervous system: chronic progressive myelopathy due to HTLV-1. PMID- 2896302 TI - [Sulfasalazine as an antirheumatism agent; a review of the literature]. PMID- 2896300 TI - Detection of human T-cell lymphoma/leukemia virus type I DNA and antigen in spinal fluid and blood of patients with chronic progressive myelopathy. AB - The presence of antibodies to human T-cell lymphoma/leukemia virus Type I (HTLV I) has been associated with chronic progressive myelopathy. We attempted to isolate the virus from the blood and spinal fluid of patients with chronic progressive myelopathy and to define the clinical, radiologic, and electrophysiologic features of this disease. Ten of 13 patients from tropical countries and 2 of 8 from the United States had serum antibodies to HTLV-I. The virus was detected in cultures of peripheral-blood lymphocytes from three of seven patients by means of Southern blot hybridization. Using a sensitive in vitro enzymatic gene-amplification technique, we detected HTLV-I sequences in fresh peripheral-blood mononuclear cells of all of 11 patients tested who were positive for the antibody, and in cell cultures of the spinal fluid from 3 of the 11 tested. Magnetic resonance imaging of the cranium revealed periventricular lesions in the white matter of 3 of the 12 antibody-positive patients. Five of these patients had mild axonal sensorimotor polyneuropathy, and one had bilateral lumbar radiculopathy. Visual evoked potentials were abnormal in three seropositive patients, and brain-stem evoked responses were abnormal in two. The detection of the DNA and proteins of HTLV-I strengthens the proposition that this virus is involved in the pathogenesis of a subset of cases of chronic progressive myelopathy. PMID- 2896303 TI - [Alpha-receptor blocking agents and centrally acting antihypertensive agents]. PMID- 2896304 TI - [Consensus policy in undescended testicle]. PMID- 2896305 TI - [Mechanisms of the suppression of the nociceptive reflex of the opening of the mouth during stimulation of the structures of the limbic brain]. AB - The comparative effectiveness of the inhibitory influence of tetanic stimulation of hypothalamus, amygdala and limbic cortex on EMG-response of m. digastricus evoked by electrical stimulation of tooth pulp nociceptive afferents was studied in cats anesthetized with a mixture of chloralose and nembutal. It was found that inhibition of the EMG-component of the jaw-opening reflex is most pronounced in case of stimulation of medial and lateral region of the hypothalamus, the inhibitory effect of central and medial nuclei of the amygdala is less pronounced and the effect of the limbic cortex is the weakest. It was shown that the mechanism of the antinociceptive effect of tetanic stimulation of the hypothalamus is not related to the concomitant increase of the blood pressure. After stabilization of the blood pressure the suppressive effect of the hypothalamus remains without changes, that points out to a direct, primary, not baro-afferent mechanism of the inhibition of the activity of nociceptive neurons of the trigeminal sensory nuclei. Noradrenaline, injected intravenously, induced a large increase of the blood pressure accompanied by a pronounced inhibition of the pain reflex. Angiotensin causes the same degree of blood pressure elevation without changes in the amplitude of the EMG-response of the pain reflex. Hypothalamic and noradrenergic mechanisms for control of pain sensitivity are discussed. PMID- 2896306 TI - [Neuroleptic malignant syndrome (dopamine-dependent malignant hyperthermia). 4 different cases]. PMID- 2896307 TI - Successful symptomatic treatment of malignant carcinoid syndrome with the somatostatin analogue SMS 201-995. PMID- 2896309 TI - Beta endorphin and dynorphin levels in rat pituitary and hypothalamus: age studies. AB - The content of immunoreactive (ir)-beta-endorphin, ir-dynorphin 1-17, and ir dynorphin 1-8 was determined in hypothalamus, anterior pituitary, and neurointermediate lobe of rats 3-24 months of age. In the anterior pituitary ir beta-endorphin showed a progressive rise with age (0.5 +/- 0.06 ng/tissue at 3 months to 1.02 +/- 0.23 at 24 months); a similar change was seen in ir adrenocorticotropic hormone content of the same tissues. No age-related change in neurointermediate lobe ir-endorphin content was observed. In the hypothalamus, the ir-beta-endorphin content fell progressively from 3 to 18 months, but was restored at 24 months to levels indistinguishable from those at 3 months (16.2 +/ 4.3 ng/tissue compared with 11.3 +/- 4.0 at 24 months). The ir-dynorphin content did not change progressively over the age span examined, except in the case of anterior pituitary content of ir-dynorphin 1-17 which fell progressively between 3 and 18 months (from 1.65 +/- 0.15 ng/tissue at 3 months to 0.73 +/- 0.12). Radioimmunoassay following high-performance liquid chromatography analysis of extracts of the tissues showed little variation of the immunoreactive forms with age, with two notable exceptions. In the hypothalamic extracts from 24-month-old rats the ratio of the nonacetylated ir-endorphin to the acetylated ir-endorphin was lower than in equivalent extracts from 3-month-old rats. In anterior pituitary extracts from 3-month-old rats, ir-dynorphin 1-17 appeared as two peaks (putative 6K and 4K species) of approximately equal size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896308 TI - Changes in the content of glutamate and GABA in the cerebellar vermis and hemispheres of the Purkinje cell degeneration (pcd) mutant. AB - The contents of glutamate and GABA, as well as aspartate, glycine, and alanine, were examined in the cerebellar vermis and hemispheres of normal and Purkinje cell degeneration (pcd) mutant mice at 6, 9, and 12 months of age. Relative to normal values, the content of glutamate was approximately 50% lower in the vermis for the 3 age groups. In the hemispheres, the content of glutamate was also lower than control values and showed a progressive loss from 30 to 47% with age. On the other hand, in the case of GABA in the vermis, the level was 39% lower in the pcd mutant at 6 months of age but no different from control values at 12 months. However, relative to data for normal mice, the content of GABA in the hemispheres was consistently lower (20%) for all age groups. The level of aspartate was approximately 60% lower in the cerebellar vermis and 45 to 55% lower in the hemispheres of the mutant with respect to control data for all three age groups. Likewise, alanine showed a reduced content in the hemispheres (36-46%) and vermis (24%) in the mutant relative to normal values at 6, 9, and 12 months of age. On the other hand, the level of glycine was 43-64% higher in the vermis and 77-100% greater in the hemispheres of the mutant than in the control group. The higher values for glycine were observed at the two oldest ages. In conclusions, the data are consistent with the idea that glutamate and GABA are present in high concentrations in granule and Purkinje cells, respectively, and provide additional support for a transmitter function for both amino acids in the cerebellum. PMID- 2896310 TI - Evidence for a dopaminergic mechanism for the prolactin inhibitory effect of atrial natriuretic factor. AB - Infusion of 2 nmol atrial natriuretic factor (ANF) into the third cerebroventricle of conscious, orchidectomized male rats results in a significant inhibition of prolactin (PRL) secretion. This effect is prevented by prior treatment with the dopamine receptor antagonist, domperidone. Furthermore, domperidone reverses the inhibitory effect when given after ANF infusion. The PRL inhibiting effect is absent as well following inhibition of tyrosine hydroxylase activity. These results suggest that ANF acts centrally at least in part via an interaction with endogenous dopaminergic systems and further suggests potent neuromodulatory actions of the peptide within the hypothalamus. PMID- 2896311 TI - Alzheimer's disease: advances in basic research and therapies. PMID- 2896313 TI - Responses resembling defensive behaviour produced by microinjection of glutamate into superior colliculus of rats. AB - Electrical stimulation of the superior colliculus in rats elicits not only orienting movements, as it does in other mammals, but also behaviours resembling such natural defensive responses as prolonged freezing, cringing, shying, and fast running and jumping. To investigate the location of the cells mediating these behaviours, the superior colliculus was systematically mapped with microinjections of sodium L-glutamate (50 mM, 200 nl), and the resultant behavioural changes as assessed in an open field were analysed for defence-like responses. The main regions that gave defensive behaviour were (i) rostromedial superior colliculus (all layers), and (ii) both medial and lateral parts of the caudal deep layers. Cells in these areas project into the ipsilateral descending pathway. However, the cells of origin of this pathway are also found in collicular regions, such as rostral intermediate gray and parts of far caudal colliculus, that did not give defensive movements in response to glutamate stimulation. It is unclear whether this is because only parts of the ipsilateral pathway mediate defensive behaviours, or because glutamate is a relatively inefficient stimulating agent for these systems. An unexpected feature of the results was that at a number of collicular sites the nature of the defensive response changed with successive (up to three) injections of glutamate, often appearing to become more intense. Whether the mechanism underlying this potentiation is related to the conditioning of natural defensive behaviour is unknown. PMID- 2896312 TI - Contralateral head movements produced by microinjection of glutamate into superior colliculus of rats: evidence for mediation by multiple output pathways. AB - One of the major efferent pathways of the superior colliculus crosses midline to run caudally in the contralateral predorsal bundle, innervating targets in the brain stem and eventually reaching the cervical spinal cord. A variety of evidence suggests that this tecto-reticulo-spinal pathway may mediate the orienting movements that can be evoked by tectal stimulation. However, we have recently found that orienting head movements can still be obtained in rats after section of the tecto-reticulo-spinal pathway, implying that additional pathways are also involved. The present study sought to test this implication, by taking advantage of the fact that in rats the cells of origin of the tecto-reticulo spinal pathway are largely segregated within the lateral part of the stratum album intermediate. It is thus possible to find out whether orienting head movements can be produced by a cell-excitant from tectal regions that contain few cells of origin of the tecto-reticulo-spinal pathway. Hooded rats in an open field were filmed during microinjections of sodium L-glutamate (50 mM, 200 nl) into the superior colliculus, and the films analysed for the appearance of contralaterally directed movements of the head and body. Subsequent histological reconstruction of the injection sites indicated that such movements could be obtained from widespread areas within the superior colliculus, including not only lateral stratum album intermediale but also the deep layers, and parts of the medial superficial and intermediate layers. Moreover, sites in or close to lateral stratum album intermediate often gave circling movements with downward pointing head, whereas some sites outside lateral stratum album intermediale gave sustained immobility with the head pointing contralaterally and upwards. This evidence supports the view that tectal efferent pathways besides the tecto reticulo-spinal pathway are involved in the control of head movement. In addition, at least some of these pathways are not collaterals of the tecto reticulo-spinal pathway, since the movements were obtained from collicular regions with few tecto-reticulo-spinal pathway cells. Finally, the results are consistent with the view that different collicular output pathways mediate movements that have different functions. PMID- 2896314 TI - Studies on dopamine-, tyrosine hydroxylase- and aromatic L-amino acid decarboxylase-containing cells in the rat diencephalon: comparison between formaldehyde-induced histofluorescence and immunofluorescence. AB - The morphology, number and distribution of catecholaminergic neurons, as visualized either with the aluminum-catalysed formaldehyde method for catecholamines or with the immunohistochemical method for the catecholamine synthesizing enzymes tyrosine hydroxylase and aromatic L-amino acid decarboxylase, respectively, were analysed within the rat dorsal hypothalamus, ventral thalamus and adjoining regions (A11 and A13 cell groups). Both polyclonal rabbit and monoclonal mouse tyrosine hydroxylase antibodies were used in elution restaining and double-staining experiments, respectively. Some of the animals also received spinal injections of the fluorescent tracer True Blue in order to retrogradely label cells projecting to the spinal cord. With respect to the number and distribution of catecholaminergic neurons in the A11 and medial A13 cell groups, including the spinal-projecting subpopulation, the results obtained with the two methods were very similar, indicating that within these regions of the CNS the two methods in principle visualize identical cell populations. However, the catecholaminergic cells were distinctly larger and their processes appeared more extensive with the immunohistochemical method. Animals processed for immunohistochemistry exhibited a lower total number of retrogradely labelled cells in the A11 area than those analysed with aldehyde-induced fluorescence despite the fact that both methods revealed similar numbers of retrogradely labelled tyrosine hydroxylase-positive and catecholamine-containing cells, respectively. The reason for these discrepancies, which are probably of methodological nature, are discussed. While this study shows that the results obtained with the two methods within the A11 and medial A13 cell group are very similar and thus strengthens the earlier proposed concept of the organization of the diencephalospinal dopaminergic system, it also documents that in intermingling and nearby CNS regions there are cell bodies which cannot be demonstrated with the aldehyde fluorescence method, but which still contain tyrosine hydroxylase and/or aromatic L-amino acid decarboxylase-like immunoreactivity. One explanation is low levels of enzyme and/or dopamine combined with a comparatively low sensitivity of the histochemical method. Thus, neurons containing both enzymes are probably dopaminergic, even if catecholamine fluorescence cannot be demonstrated. Neurons containing tyrosine hydroxylase, but lacking both aldehyde induced fluorescence and aromatic L-amino acid decarboxylase, may also still be dopaminergic.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2896315 TI - Altered subsets of peripheral blood lymphocytes in patients with HTLV-I associated myelopathy (HAM). AB - We studied subsets of peripheral blood lymphocytes (PBL) from 12 patients with human T-lymphotropic virus type I (HTLV-I) associated myelopathy (HAM). The percent of OKT8+ cells was significantly decreased, and the percentages of OKDR+ cells and IL-2R+ cells and the ratio of OKT4+ cells to OKT8+ cells were significantly increased compared with either HTLV-I seronegative healthy adults (controls) or HTLV-I seropositive non-HAM subjects (carriers). The subsets of PBL from eight carriers showed no differences from those in controls. The patients with HAM showed significantly higher antibody titers to HTLV-I compared with carriers. These altered PBL subsets and high HTLV-I antibody titers in the patients suggest that immune functions are in an activated state in HAM. PMID- 2896316 TI - [A new H1-blocking antihistamine. Critical review of pharmacological and clinical studies]. AB - Astemizole is a long-acting antihistamine that blocks the H1 receptors. Thanks to its long-acting effect, symptoms can be controlled by a single daily dose. Its efficacy in the treatment of seasonal and permanent allergic rhinitis has been demonstrated in many studies in which it was compared with other antihistamines. It has also proved useful in the treatment of allergic conjunctivitis and chronic urticaria. Though a tendency to increased appetite and slight weight gain after prolonged use has been noted in some patients, astemizole is not sedative and has no anticholinergic effect in the standard therapeutic doses. PMID- 2896317 TI - Cerebrospinal fluid somatostatin correlates with spectral EEG variables and with parietotemporal cognitive dysfunction in Alzheimer patients. AB - Somatostatin levels of the cerebrospinal fluid (CSF) were correlated with variables of quantitative EEG and with neuropsychological performance in patients with probable Alzheimer's disease. Low somatostatin levels of CSF correlated with decreased beta activity and with decreased mean frequency in the combined alpha and theta EEG range. In the subgroup of mild Alzheimer cases CSF somatostatin correlated positively also with alpha power, and the peak and the mean frequency, and negatively with theta power but not with delta activity. Furthermore, low somatostatin of the CSF correlated with neuropsychological tests assessing temporoparietal dysfunction. To our knowledge, this is the first study to indicate the correlation between spectral analysis results of the EEG and CSF somatostatin suggesting that the relationship between somatostatin and EEG variables is worthy of further studies. PMID- 2896318 TI - Ultrastructural demonstration of the catecholaminergic innervation of vasopressin neurons in the paraventricular nucleus of the rat by double-labeling immunocytochemistry. AB - The catecholaminergic innervation of vasopressin (VP) neurons in the paraventricular nucleus (PVN) of the rat was studied at the electron microscopic level by double-labeling immunocytochemistry combining the preembedding peroxidase-antiperoxidase method with the postembedding immunogold staining method. Tyrosine hydroxylase-like immunoreactive nerve terminals were found to establish synapses with neurophysin II-like immunoreactive neuronal perikarya and their processes. This provides morphological evidence for catecholaminergic control of the release of VP, at the PVN level. PMID- 2896319 TI - Enhancement of the oxygen consumption in the hippocampal slices of the guinea pig induced by glutamate and its related substances. AB - The effects of glutamate (Glu), kainate (Ka), and N-methyl-D-aspartate (NMDA) on the oxygen consumption of the hippocampal slices of the guinea pig were investigated. The oxygen consumption of slices at resting state was 8.43 mumol/g protein/min. Bath application of Ka (1 x 10(-8) to 1 x 10(-6) M), NMDA (1 x 10( 8) M to 1 x 10(-4) M), and Glu (1 x 10(-5) M to 5 x 10(-4) M) enhanced the oxygen consumption dose-dependently in the similar tendency although the effective doses varied for the different excitants. Subsequently the consumption was maximal at approximately 140% of the resting level. The enhancement of the oxygen consumption due to NMDA and Glu was antagonized by DL-2-amino-5-phosphonovaleric acid (APV) for NMDA and by glutamic acid diethylester (GDEE) and Joro spider toxin (JSTX) for Glu. From these results it was suggested that the increase of the oxygen consumption observed here must reflect the neuronal activation induced by these excitants. PMID- 2896320 TI - Changes in the state of the excitatory synaptic system in the hippocampus on prolonged exposure to excitatory amino acids and antagonists. AB - Prolonged exposure of hippocampal slices to L-glutamate was found to produce a biphasic effect on excitatory synaptic transmission from Schaffer collateral commissural fibers to CA1 pyramidal neurons: an early blockade of postsynaptic responses was followed by a progressive recovery. Antagonists of N-methyl-D aspartate (NMDA) receptors, which had no effect on the initial responses, blocked the responses which reappeared during continued exposure to L-glutamate. Furthermore, when NMDA antagonists were maintained in the presence of glutamate, excitatory transmission was again restored and the new responses were now insensitive both to 'NMDA' and 'non-NMDA' antagonists. Once elicited, the changes in synaptic transmission appear to be 'memorized' by the slice for at least tens of minutes. These phenomena suggest that the well-known plasticity of the hippocampal synapses may involve a sequence of distinct 'states', and that transitions between these states can be induced by certain pharmacological stimuli. PMID- 2896321 TI - Stimulation of muscarinic receptor in hippocampal neuron induces characteristic increase in cytosolic free Ca2+ concentration. AB - Changes in cytosolic free Ca2+ concentration ([Ca2+]i) in response to acetylcholine (ACh) were examined by fura-2 fluorometry in cultured rat hippocampal neurons. ACh (greater than or equal to 10(-5) M) induced an increase in [Ca2+]i composed of fast transient and slow long-lasting phases. Atropine (10( 8) M) abolished the fast component and greatly reduced the slow component. The slow component was selectively blocked by pirenzepine (10(-6) M). The effect of ACh remained partially in a Ca2+-deficient medium where effects of L-glutamate and KCl (50 mM) were abolished. Present results suggest that ACh elevates [Ca2+]i by activation of muscarinic receptor subtypes, one of which is coupled with ion channels and the other of which transduces the ACh binding to mobilization of intracellularly stored Ca2+. PMID- 2896322 TI - Presynaptic and postsynaptic glutamatergic function in Alzheimer's disease. AB - Sodium dependent D-aspartate and Ca2+/Cl-independent L-glutamate binding assays were used to assess the integrity of glutamate uptake sites and postsynaptic NMDA receptor levels in control and Alzheimer's disease temporal cortex. The number of glutamate uptake sites was significantly and substantially reduced in accordance with previous findings. However, NMDA receptor levels were unchanged. This finding suggests that glutamatergic presynaptic elements are severely reduced in Alzheimer's disease, whilst postsynaptic elements remain intact. PMID- 2896323 TI - Brainstem dopaminergic neurons project to monkey parietal cortex. AB - In this study, retrograde transport of Fast blue was combined with tyrosine hydroxylase immunohistochemistry to reveal the presence of projections from both dopaminergic and non-dopaminergic neurons of the substantia nigra-ventral tegmental area to the parietal cortex of cynomolgus monkeys (Macaca fascicularis). These findings confirm the results of previous studies demonstrating the existence of a dopaminergic innervation of monkey parietal cortex. PMID- 2896324 TI - Chronic low level lead exposure precociously induces rat glial development in vitro and in vivo. AB - Lead has been demonstrated to induce precocious glial differentiation both in vitro and in vivo. Lead-treated rat glioma (C6) and cerebellar astrocytes exhibited cytoplasmic extensions and the presence of glial endfeet after a 3-day exposure to 10(-6) to 10(-4) M PbCl2. In similar experiments no effect was noted in neuroblastoma (Neuro-2a) or on neurite outgrowth from chick spinal cord explants. This prodifferentiative effect on glia was also seen in the cerebella of postnatal rats in which the developmental expression of glial-specific glutamine synthetase activity was significantly increased up to postnatal day 12 after chronic exposure to lead from time of birth via their dam's drinking water (400 mg PbCl2/l). PMID- 2896325 TI - Traumatic amputation. Action stat! PMID- 2896326 TI - Neuroleptic malignant syndrome: a review of the Wellington experience. AB - The neuroleptic malignant syndrome is a potentially lethal complication of central dopamine antagonism. We report five cases, occurring in the Wellington region in the last 4 years. Three of the cases are reported in detail and the diagnostic difficulties and therapeutic strategies are reviewed. Particular attention is drawn to the use of the depot intramuscular phenothiazine formulations which were clearly implicated in our experience. PMID- 2896327 TI - [Treatment of glaucoma with beta receptor blockers. Significance of adrenergic receptors of the beta-2 subtype for their effect on intraocular pressure]. AB - After 20 years of extensive practical experience in the management of glaucoma, beta-adrenergic blocking agents have gained a continuously increasing importance. The reason is a combination of effective reduction of intraocular pressure even during chronic treatment and few adverse effects. For many years, substantial effort has been focussed on the elucidation of the cellular mechanism inducing the intracellular pressure reduction. In this respect, mainly three different hypotheses have been controversially discussed: beta-blockers reduce aqueous humor formation (1) by an unspecific membrane-stabilizing process, (2) by impeding the local circulation of the ciliary body or (3) by specifically blocking adrenergic beta-receptors intimately involved in the regulation of aqueous humor production. Recently, substantial progress has been achieved by different working groups getting highly purified melanin-depleted fractions of ciliary epithelia which allow accurate receptor-ligand binding studies. The most important results, which all favor the explanation that the mechanism of action is due to specific inhibition of adrenergic receptors of the beta-2-subtype, are presented here. The consequences which result for the development of more specific pharmacologic agents in the future are discussed. PMID- 2896328 TI - [Neuroendocrine regulation of adaptation]. PMID- 2896329 TI - Monoclonal antibodies specific for the neu oncogene product directly mediate anti tumor effects in vivo. AB - We have produced a panel of monoclonal antibodies which bind cell surface domains of the 185 Kd tumor antigen (p185) encoded by the neu oncogene. All of these antibodies stain neu-transformed cells in immunofluorescence assays and immunoprecipitate p185 from metabolically labeled cell lysates. All of the anti p185 monoclonal antibodies, regardless of isotype, exert a selective cytostatic effect on the growth of neu-transformed cells suspended in soft agar, demonstrating their ability to directly inhibit the transformed phenotype. Anti p185 antibodies of the IgM, IgG2a, and IgG2b isotypes exert a cytolytic effect on neu-transformed cells in the presence of complement. Only one IgG2a monoclonal antibody is also able to mediate minimal levels of antibody-dependent cellular cytotoxicity (ADCC) (Roussel et al., 1984) in the presence of non-immune spleen cells. In vivo administration of anti-p185 antibodies of the IgG1, IgG2a, and IgG2b isotypes exerts a profound inhibitory effect on the tumorigenic growth of neu-transformed cells. This tumor inhibitory effect is unaffected by depleting tumor bearing animals of complement, and is only minimally affected by depleting tumor bearing animals of macrophages. This suggests that neither complement mediated killing nor ADCC are necessary for the anti-tumor effects of p185 specific monoclonal antibodies. The results presented here demonstrate that monoclonal antibodies reactive with cell surface domains of an oncogene-encoded protein can directly inhibit tumor growth in vitro and in vivo. Such antibodies may prove useful in the therapy of certain malignancies. PMID- 2896330 TI - Retroviral heterogeneity in mouse lymphomas. AB - Provirus modifications which can occur in tumors may lead to tumor antigenic variants. To investigate this possibility we compared the restriction fragment length patterns of mouse mammary tumor virus (MMTV), murine leukemia virus and xenotropic and mink cell-focus inducing (MCF)-related sequences, using Southern blot analysis, in a panel of Balb/c and C57BL/6 lymphomas, some of which were known to express novel histocompatibility (H) antigens. The results indicate differences in amplification and novel integration sites of retroviral sequences in all tumors analyzed, the number of new sequences depending on the specific retroviral sequence. A relationship has been found between integration of new MMTV sequences and a known susceptibility to lysis by syngeneic alloactivated lymphocytes in the same group of tumors. The possibility that retroviruses can induce the expression of novel histocompatibility antigens on tumors is discussed. PMID- 2896331 TI - Bethanechol chloride as a suggested adjunct to prolonged in vivo exposure therapy in the treatment of paruresis. AB - A major difficulty in treating paruresis (psychogenic urinary retention) by prolonged in vivo exposure therapy involves the individual's inability to initiate urination in response to anxiety-provoking stimuli easily and frequently enough to generalize the desired behavior to everyday situations. Administration of bethanechol chloride, a parasympathomimetic compound that facilitates urination by prompting contraction of the detrusor muscle of the bladder, prior to therapeutic sessions is suggested to enhance the efficiency and effectiveness of in vivo desensitization procedures in the treatment of paruresis. PMID- 2896332 TI - Nucleotide sequence of the Hox2.3 gene region. PMID- 2896333 TI - Sequence analysis of three polymorphic regions in the human genome detected by the G8 probe for RFLPs associated with Huntington's disease. PMID- 2896334 TI - Eco RI RFLP in the human IGF II gene. PMID- 2896335 TI - Two polymorphic loci are detected simultaneously by probe CARLP II8.2 [D10S21] on chromosome 10. PMID- 2896336 TI - RFLP identified by the anonymous DNA segment FZ VI A2 at 22q11.2 [HGM no. D22S20]. PMID- 2896337 TI - Isolation and mapping of a polymorphic DNA sequence pXH3 on chromosome X [DXS235]. PMID- 2896339 TI - A Taq I polymorphism in the 5' region of the von Willebrand factor (vWF) gene. PMID- 2896338 TI - Bst NI (Eco RII) RFLP in the lipoprotein lipase gene (LPL). PMID- 2896340 TI - A TaqI RFLP demonstrated for pIBS17 [D4S123], a single copy sequence on chromosome 4. PMID- 2896341 TI - Polymorphisms revealed by random probe H2-10 [D13S26] which maps to chromosome 13q21-q22. PMID- 2896342 TI - Localization of CRF-like immunoreactivity in the brain and pituitary of teleost fish. AB - Immunocytochemical techniques were applied to brain and pituitary sections of eleven teleost species. A corticotropin-releasing factor (CRF)-antiserum allowed the identification of a CRF-like system in these species. Perikarya were labeled in the preoptic nucleus. Labeled fibers were traced laterally, then ventrally close to the optic chiasma, forming two symmetrical tracts running through the basal hypothalamus. These ended in the rostral neurohypophysis (NH) close to ACTH cells as shown by double immunostaining. Other fibers, often more variquous, ended in the caudal NH close to melanocorticotropic cells. In Salmo fario, small perikarya also stained in the nucleus lateralis tuberis. The CRF-like system appears distinct from that of somatostatin. In Anguilla, adjacent sections stained with CRF- and vasotocin (AVT)-antisera respectively showed that these two peptides coexist in some perikarya. As few fibers containing only AVT end in the rostral NH, they probably do not control ACTH cells directly. AVT fibers terminate mostly in the caudal NH close to melanocorticotropic cells. Some extra hypothalamic fibers suggest that CRF may also act as a neurotransmitter. The plurality of hormones showing a CRF-like activity in teleosts is considered. PMID- 2896344 TI - Food intake in rats is increased by intracerebroventricular infusion of the somatostatin analogue SMS 201-995 and is decreased by somatostatin antiserum. AB - The chronic intracerebroventricular infusion of the somatostatin analogue SMS 201 995 resulted in a significant increase in daily food intake which was accompanied by an unexpected body weight loss. The neutralisation of central somatostatin using a specific somatostatin antiserum resulted in a significant decrease in daily food intake. These results suggest that endogenous somatostatin in the brain can drive feeding behavior and alter body weight. PMID- 2896343 TI - Pharmacokinetic evaluation of superactive analogues of growth hormone-releasing factor (1-29)-amide. AB - D-amino acid-substituted analogues of growth hormone-releasing factor 1-29)-amide with superagonist activities in the rat were examined for increased plasma half life and resistance to degradation in vivo. After IV injection, half-lives of the analogues were in the range 4.7-7.4 min, none of which was significantly different from that of the parent compound (6.2 min). Following SC injection, 4.6 7.2% of the dose of the analogues reached the circulation compared with 5.1% of the parent compound. Conformational restraints introduced into the N-terminal region of the molecule, which gave enhanced potency, did not alter the susceptibility of the peptide to proteolytic degradation. PMID- 2896346 TI - Relationships between drug regime and histology of rectal mucosa in Crohn's disease. AB - In the scope of the ECCDS, testing the efficacy of prednisolone and/or sulfasalazine in Crohn's disease, the relationships between drug regime and histology of rectal mucosa were studied. Rectal biopsies, gained at start and after termination of treatment were available in 57 patients. Additionally, biopsies of 20 normal controls were studied. The biopsies, cut completely in serial sections, were investigated by quantitative histological methods. The data were evaluated by multivariate discriminant analyses. The nearest approach of histologic pattern to normal was found after combined treatment with prednisolone and sulfasalazine, followed by prednisolone monotherapy. The effect of sulfasalazine as monotherapy was poor. The degree of normalisation in histologic pattern agrees very well with the CDAI in our subsets. Overall, effective therapy was reflected in histology of rectal mucosa by a decrease of acute inflammatory alterations and an increase of mononuclear infiltration. Only minor individual effects of the various drug regimes were found. PMID- 2896345 TI - Thyrotropin-releasing hormone blocks neurally-mediated hyperglycemia through central action. AB - Central injection of thyrotropin-releasing hormone (TRH) potently blocked the development of, as well as rapidly reversed, 2-deoxyglucose (2-DG)-stimulated hyperglycemia in mice. The antihyperglycemic effect was dose-related, dependent upon the structural integrity of the peptide, dissociated from the peptide's hypophysiotropic action and from its interaction with TRH receptors, and mediated by the cholinergic parasympathetic system. Moreover, TRH blocked the rise in plasma glucose following central injection of corticotropin-releasing factor, enkephalin, clonidine and glucagon, as well as the hyperglycemic response to immobilization, electric foot shock or endotoxin administration. These results indicate that TRH, acting within the central nervous system, can block neurally mediated hyperglycemia in addition to its previously reported actions to elicit systemic hypoglycemia in normoglycemic mice and to antagonize epinephrine stimulated hyperglycemia in these animals. PMID- 2896347 TI - Anxiety disorders. Can you give me something for my nerves, doctor? AB - The antianxiety drugs available today are highly effective. Before prescribing anxiolytics, the physician needs to carefully evaluate the patient to determine if true symptoms of anxiety are present and are interfering with the patient's functioning. Patient education about the cause of the disorder and the purpose of anxiolytic therapy is essential for successful management. Selection of the proper drug dose must be individualized, and regular patient monitoring is necessary to detect side effects or possible drug abuse. Careful record keeping is the best defense against legal problems arising from a patient's abusing or diverting of prescribed drugs. PMID- 2896348 TI - Differential expression of class II major histocompatibility complex and Thy 1.2 antigens on mouse decidua. AB - A differential expression of class II major histocompatibility complex (MHC) and Thy 1.2 antigens was detected on two morphologically distinct cell populations in short-term cultures of murine decidual tissue. Stromal type decidual cells expressed Thy 1.2, albeit transiently, and consistently lacked class II antigens. By contrast decidual macrophages expressed class II antigens and lacked Thy 1.2 antigens. Stromal type decidual cells, after culture in the presence of indomethacin, displayed no evidence of prostaglandin-mediated modulation of class II expression. These findings suggest that class II positive decidual macrophages are responsible for the antigen-presenting capacity of decidua. PMID- 2896349 TI - [Circulating hematopoietic cells. Results of 6 autologous grafts]. AB - Six patients with acute non-lymphocytic leukemia underwent autologous transplantation of circulating stem cells collected during remission. They were given cyclophosphamide (120 mg/kg) and total body irradiation (1,000-1,200 rads) (five patients) or busulfan (16 mg/kg) and melphalan (140 mg/m2) before the transfusion of 6.7 X 10(8) nucleated cells/kg corresponding to 19.7 X 10(4) CFU GM/kg. Granulopoietic engraftment was observed in every case and was influenced by the number of CFU-GM injected. Megakaryocytic recovery was obtained in four cases. PMID- 2896350 TI - [Euthyroid goiter: the autoimmune component of its pathogenesis]. PMID- 2896351 TI - Pancreatic secretagogues regulate somatostatin binding to its receptors on rat pancreatic acinar membranes. AB - Labeled somatostatin binding to pancreatic acinar membranes was examined to investigate how pancreatic secretagogues regulate somatostatin receptors in the pancreas. Pretreatment of pancreatic acini at 37 degrees C for 120 min with not only pancreatic secretagogues, such as carbachol and bombesin, but also vasoactive intestinal peptide (VIP) and secretin reduced subsequent labeled somatostatin binding to the acinar membranes in a dose-dependent manner. The inhibitory effects of these secretagogues on labeled somatostatin binding were also time dependent. Both types of secretagogues maximally reduced subsequent somatostatin binding when acini were incubated with them for more than 120 min. However, the degree of the inhibition was greater with carbachol or bombesin than VIP or secretin; the former secretagogues reduced the binding to 40-45%, and the latter to 75-80% of a control, respectively. These pancreatic secretagogues had no inhibitory effect on somatostatin binding when added directly to the binding media. Furthermore, the inhibitory effect of carbachol was attenuated by the presence of 1 mM EDTA in media for pretreatment, suggesting that intracellular pathways activated by pancreatic secretagogues may be responsible for somatostatin receptor modulation. Interestingly, when combined with VIP, pretreatment of acini with carbachol produced an additive inhibition of labeled somatostatin binding to the membranes. Results, therefore, suggest that somatostatin binding to its receptors in the pancreas may be regulated via two functionally distinct intracellular pathways. PMID- 2896352 TI - Colocalization of calcitonin gene-related peptide and somatostatin in pancreatic islet cells and inhibition of insulin secretion by calcitonin gene-related peptide in the rat. AB - Calcitonin gene-related peptide (CGRP)- and somatostatin (SRIF)-containing cells were identified by immunocytochemical techniques in pancreatic islet cells of the rat. CGRP-containing cells were found primarily in the peripheral portion of the pancreatic islets. In addition, CGRP-containing cells also contained somatostatin, which identifies the islet CGRP-containing cells as D cells. In the present study, we also tested the effect of CGRP on gastrin-releasing peptide (GRP; 10(-9) M)- or cholecystokinin (CCK-8, 10(-9) M)-stimulated release of insulin from isolated rat islets in vitro. At concentrations of 10(-8)-10(-11) M, CGRP inhibited GRP- and CCK-8-stimulated release of insulin significantly when compared with GRP or CCK-8 alone. At the lowest concentration of CGRP (10(-11) M), the inhibitory effect of CGRP on CCK-8-stimulated release of insulin was statistically significant (p less than 0.05) and exceptionally potent (65-90% inhibition). We have also found that CGRP does not stimulate the release of SRIF from isolated islet cells. These findings suggest that CGRP may play a regulatory role in the release of insulin. PMID- 2896353 TI - Isolation and sequence of a cDNA clone encoding the 31-kDa subunit of bovine kidney vacuolar H+-ATPase. AB - We have isolated a cDNA encoding the 31-kDa subunit of the bovine kidney vacuolar H+-ATPase. The composite sequence contains 1219 base pairs, which includes the entire 678-base-pair coding region. A lysine-rich sequence previously found in the Na+, K+-ATPase alpha subunit and the H+,K+-ATPase was identified in the 31 kDa subunit. An RNA blot and an immunoblot demonstrated variable 31-kDa subunit expression and immunoreactivity in different tissues; the highest levels were observed in kidney medulla and brain with both types of analysis. The isolation of a cDNA for the 31-kDa subunit is an important step in understanding this subunit's role in the function and regulation of the vacuolar H+-ATPase. PMID- 2896354 TI - Developmental regulation of constitutive and inducible expression of hepatocyte specific genes in the mouse. AB - Deletions in chromosome 7 of the mouse have been shown to cause failure of expression of certain liver-specific enzymes in newborn deletion homozygotes. Among these enzymes are L-tyrosine:2-oxoglutarate aminotransferase (EC 2.6.1.5) and phosphoenolpyruvate carboxykinase (GTP) [GTP:oxaloacetate carboxy-lase (transphosphorylating); EC 4.1.1.32]. The studies reported here show that in fetal stages constitutive expression of the relevant genes on the level of steady state mRNA is identical in the livers of homozygous deletion mutants and normal littermates. Furthermore, prenatally these enzymes are expressed also in cell types other than hepatocytes. Thus, the putative trans-acting regulatory factors encoded in the deleted region of chromosome 7 of the mouse appear to be concerned specifically with the regulation of cell type-specific inducible expression of various hepatocyte-specific genes, whereas constitutive expression of the same genes is not affected. PMID- 2896355 TI - Nonrandom X chromosome inactivation in B cells from carriers of X chromosome linked severe combined immunodeficiency. AB - X chromosome-linked severe combined immunodeficiency (XSCID) is characterized by markedly reduced numbers of T cells, the absence of proliferative responses to mitogens, and hypogammaglobulinemia but normal or elevated numbers of B cells. To determine if the failure of the B cells to produce immunoglobulin might be due to expression of the XSCID gene defect in B-lineage cells as well as T cells, we analyzed patterns of X chromosome inactivation in B cells from nine obligate carriers of this disorder. A series of somatic cell hybrids that selectively retained the active X chromosome was produced from Epstein-Barr virus-stimulated B cells from each woman. To distinguish between the two X chromosomes, the hybrids from each woman were analyzed using an X-linked restriction fragment length polymorphism for which the woman in question was heterozygous. In all obligate carriers of XSCID, the B-cell hybrids demonstrated preferential use of a single X chromosome, the nonmutant X, as the active X. To determine if the small number of B-cell hybrids that contained the mutant X were derived from an immature subset of B cells, lymphocytes from three carriers were separated into surface IgM positive and surface IgM negative B cells prior to exposure to Epstein-Barr virus and production of B-cell hybrids. The results demonstrated normal random X chromosome inactivation in B-cell hybrids derived from the less mature surface IgM positive B cells. In contrast, the pattern of X chromosome inactivation in the surface IgM negative B cells, which had undergone further replication and differentiation, was significantly nonrandom in all three experiments [logarithm of odds (lod) score greater than 3.0]. These results suggest that the XSCID gene product has a direct effect on B cells as well as T cells and is required during B-cell maturation. PMID- 2896356 TI - Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells. AB - Normal differentiation and malignant transformation of human cells are characterized by specific changes in surface antigen phenotype. In the present study, we have defined six cell-surface antigens of human sarcomas and normal mesenchymal cells, by using mixed hemadsorption assays and immunochemical methods for the analysis of cultured cells and immunohistochemical staining for the analysis of normal tissues and greater than 200 tumor specimens. Differential patterns of F19 (Mr, 120,000/95,000 glycoprotein), F24 (Mr, 95,000 glycoprotein), G171 (Mr, 75,000 glycoprotein), G253 (Mr, 90,000 glycoprotein), S5 (Mr, 120,000 glycoprotein), and Thy-1 (Mr, 25,000 glycoprotein) antigen expression were found to characterize (i) subsets of cultured sarcoma cell lines, (ii) cultured fibroblasts derived from various organs, (iii) normal resting and activated mesenchymal tissues, and (iv) sarcoma and nonmesenchymal tumor tissues. These results provide a basic surface antigenic map for cultured mesenchymal cells and mesenchymal tissues and permit the classification of human sarcomas according to their antigenic phenotypes. PMID- 2896358 TI - Studies on metabolic regulation and estimation of sialic acids by enzyme immobilization techniques. PMID- 2896357 TI - Bradykinin as a pain mediator: receptors are localized to sensory neurons, and antagonists have analgesic actions. AB - Autoradiographic studies localize [3H]bradykinin receptor binding sites to the substantia gelatinosa, dorsal root, and a subset of small cells in both the dorsal root and trigeminal ganglia of the guinea pig. [3H]Bradykinin labeling is also observed over myocardial/coronary visceral afferent fibers. The localization of [3H]bradykinin receptors to nociceptive pathways supports a role for bradykinin in pain mediation. Several bradykinin antagonists block bradykinin induced acute vascular pain in the rat. The bradykinin antagonists also relieve bradykinin- and urate-induced hyperalgesia in the rat paw. These results indicate that bradykinin is a physiologic mediator of pain and that bradykinin antagonists have analgesic activity in both acute and chronic pain models. PMID- 2896360 TI - Stimulus properties of 1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDA) analogs. AB - Using a standard two-lever operant procedure, groups of rats were trained to discriminate intraperitoneal doses of the phenylisopropylamines (+)amphetamine (1.0 mg/kg) or racemic 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM; 1.0 mg/kg) from saline using a VI 15-sec schedule of reinforcement for food reward. Once trained, the animals were administered doses of several methylenedioxy analogs (MDAs) of phenylisopropylamine including the N-monomethyl [S(+)MDMA and R(-)MDMA], N-monoethyl [(+/-)MDE, S(+)MDE, and R(-)MDE], and the N-hydroxyl [(+/ )N-OH MDA] derivatives. The DOM-stimulus did not generalize to any of these agents. The amphetamine-stimulus generalized to S(+)MDMA, S(+)N-ethylamphetamine and (+/-)N-hydroxyamphetamine, but not to R(-)MDMA, (+/-)MDE, S(+)MDE, R(-)MDE, or N-OH MDA. The present results are consistent with other reports in the literature suggesting that the psychoactive effects of certain MDA derivatives may be other than simply amphetamine- or DOM-like. PMID- 2896359 TI - Zuclopenthixol and melperon in the treatment of elderly patients: a double-blind, controlled, multi-centre study. AB - A double-blind study was carried out in 53 elderly patients in 6 geriatric nursing homes to assess the effectiveness of the neuroleptics, zuclopenthixol and melperon (flubuperone), in the relief of restlessness, aggressiveness and other such symptoms. The initial daily dose was 4 mg zuclopenthixol or 75 mg melperon, increased if necessary over the treatment period of 4 weeks. Assessments were made on entry and after 1, 2 and 4 weeks of treatment of the overall severity of illness and of individual symptoms. The results showed that there was significant improvement in the condition of patients in both treatment groups and a significant reduction in mean total as well as in the main single symptom scores. These changes were already apparent after 1 week of treatment. Although there was a tendency for faster improvement in the zuclopenthixol group, there were no significant differences between the groups in any of the parameters assessed. Side-effects were few and generally mild and transient. PMID- 2896361 TI - Nocturnal depletion of hypothalamic dynorphin in anorexic Walker-256 tumor bearing rats. AB - Rats implanted with the Walker-256 (W-256) tumor exhibit marked anorexia that is most apparent at night. In this model, the hypothalamic kappa opioid system was examined for deficits that might contribute to this tumor-induced anorexia. In anorexic tumor-bearing rats (TBR), nocturnal levels of ir-DYN-8 were significantly reduced in the hypothalamus, but ir-DYN-17 levels were not. Accumulation of 3H-etorphine or 3H-ethylketocyclazocine, a putative ligand for the kappa receptor subtype, was not increased in the hypothalamus of the TBR, as might have been expected if there were less endogenous dynorphin to occupy the opioid receptors in this region. In vitro binding assays with 3H ethylketocyclazocine indicated that dynorphin depletion in the TBR was not sufficient to increase the numbers of kappa opioid receptors in the hypothalamus. Also, the sensitivity of kappa opioid receptors involved in feeding was not altered in the TBR as indicated by an intact feeding response to ketocyclazocine. In summary, the marginal deficits of hypothalamic dynorphin in W-256 tumor bearing rats that coincide with the phase of tumor-induced anorexia may contribute to the reduction in food intake. PMID- 2896362 TI - Convulsant versus typical barbiturates: effects on conflict behavior in the rat. AB - Typical barbiturates produce a spectrum of behavioral effects, including anti convulsant, muscle relaxant, sedative hypnotic and anti-anxiety actions. In contrast to these typical barbiturates, there exists a group of barbiturates which are pro-, rather than anti-convulsant. The effects of these convulsant barbiturates on anxiety-related behaviors have not been examined. Therefore, the present studies were designed to compare the effects of the convulsant barbiturate CHEB to those of a number of typical barbiturates in the Conditioned Suppression of Drinking (CSD) paradigm, an "animal model" for the study of anxiety and anti-anxiety agents. In daily 10-minute sessions, water-deprived rats were trained to drink from a tube which was occasionally electrified (0.5 mA), electrification being signalled by a tone. Within 3-4 weeks control responding had stabilized (10-15 shocks and 10-15 ml water/session); drug tests were then conducted at weekly intervals. Consistent with previous reports, typical barbiturates (pentobarbital, secobarbital, phenobarbital) produced dose-dependent increases in the number of shocks received at doses which did not depress background responding (water intake). In contrast, sub-convulsant doses of CHEB (0.3-2.5 mg/kg) produced a dose-dependent depression of both punished responding and background responding. Finally, it was found that pre-treatment with 1.25 mg/kg CHEB did not alter the anti-conflict effects of pentobarbital. These results suggest that (1) convulsant and typical barbiturates have markedly different effects on conflict behavior in the rat and (2) CHEB appears not to possess any "barbiturate antagonist" qualities. PMID- 2896365 TI - Italian Pharmacological Society, 1st inter-regional meeting. Pavia, October 5, 1987. Pharmacology of neurotransmission. Reviews and communications. PMID- 2896363 TI - Methysergide potentiates the hyperactivity produced by MDMA in rats. AB - Although some substituted amphetamines, like MDA, produce a combination of sympathomimetic stimulation and perceptual alterations, the psychoactive qualities of MDMA are less distinctive. MDMA binds to serotonergic receptors and has been shown to potently deplete brain serotonin concentrations. Biochemical and behavioral evidence suggests that MDMA may also act on the dopamine system. The present study explored the effects of blocking serotonin receptors on MDMA and amphetamine induced locomotor hyperactivity in rats. Locomotor activity was measured in photocell cages for 120 minutes following injection of methysergide (0, 2.5, 5, 10 mg/kg) or methysergide in combination with amphetamine (0.5 mg/kg) or MDMA (10 mg/kg). Methysergide, which had no effect on its own, significantly potentiated the locomotor hyperactivity produced by MDMA but not amphetamine. Thus, the intrinsic serotonergic agonist properties of MDMA may actually counteract the indirect sympathomimetic effects thought to be responsible for the locomotor hyperactivity MDMA produces. PMID- 2896364 TI - Effect of mifentidine on mepirizole-induced duodenal ulcer in the rat. AB - The H2-receptor antagonists mifentidine, famotidine, cimetidine and ranitidine were examined for their ability to prevent the duodenal ulcer caused by mepirizole (250 mg/kg p.o.), a non-steroidal anti-inflammatory agent, in the conscious rat. All the compounds exerted a dose-related protective effect and on the basis of their ED50s, the following rank order of potency was found: mifentidine = famotidine greater than ranitidine greater than cimetidine. The antiulcer activity displayed by the H2-receptor antagonists evaluated in this model reflects their potency in inhibiting basal and stimulated gastric acid secretion in rat. The results of these studies indicate mifentidine as a potent anti-ulcer agent. PMID- 2896366 TI - Release in vitro as a model to study neurotransmitter receptors. PMID- 2896368 TI - Pharmacologic management of glaucoma. PMID- 2896367 TI - [Changes in the system of cyclic nucleotides in irradiated body tissues]. AB - It has been shown that the content of cAMP in the rat thymus, spleen, and liver 1 and 3 days after gamma-radiation with 7.5 Gy decreases, and that of cGMP increases. Analogous dynamics has been revealed when studying adenylate cyclase and guanylate cyclase activities. The activity of cAMP and cGMP phosphodiesterases increased during the first period of study but subsequently it showed no distinction from the initial data level. The revealed postradiation changes in the content of cyclic nucleotides seem to be basically caused by the cyclases activity alterations. PMID- 2896369 TI - Astroglia from defined brain regions as studied with primary cultures. PMID- 2896370 TI - Pharmacology of the glutamate receptor. AB - Glutamate is a potent candidate of the excitatory transmitter at the invertebrate NMJ and the synapse of the vertebrate CNS. But pharmacological studies have not been enough to prove that glutamate functions as an excitatory neurotransmitter. During the past 10 years, we have been studying the effects of various compounds which demonstrate the glutamate blocking action, but the glutamate responses are more effectively blocked by the drugs than the nerve-evoked synaptic response. A marked difference was revealed by TI-233, the minimum concentration of TI-233 on EJP being about a hundred times greater than the minimum threshold concentration on the glutamate-induced responses. The subsequent studies demonstrated that the action of TI-233 was able to be explained by the open channel block of the glutamate-activated ion-channel. The difference does not confute the hypothesis that glutamate is the natural transmitter substance at the crayfish NMJ, notwithstanding the fact that the action of the transmitter candidate on the postsynaptic membrane must be identical in every respect with that of the transmitter. Once something potentially useful has been found it is necessary to know not only what a substance does but how well it does it, so that comparisons can be made and better drugs discovered. Our first task therefore was to find a powerful glutamate blocker. Recently, as a result of synthesizing a series of compounds on the base of the structure-activity relationship in drug design, a series of compounds was found to reduce markedly glutamate responses at the crayfish NMJ and the mammalian central neurones at extremely low concentrations. In addition, a novel potent excitatory amino acid, acromelic acid, was found. This compound markedly excites the crayfish opener muscle and the mammalian central neurones. Agonists and antagonists have provided a very useful tool for neuroscience research, and findings of these new pharmacological tools will lead to progress in pharmacological studies to elucidate the function of glutamate in the body, in addition to other established compounds. The recent advances in our limited understanding of pharmacology of the glutamate receptor are discussed here. PMID- 2896371 TI - Notes on human behavioural pharmacotoxicology. AB - 1. After 30 years of psychopharmacological therapy we are able to identify some aspects which can be referred to a "collateral behavioural effect". The apparent rarity of this depends on the facility of confusing behavioural modifications (often sine materia), with patological ones (normally of a physical nature). 2. Memory, learning, the ability of evoking, problems regarding reality, paradoxical reactions, "makefobic" behaviour, passivity and social and behavioural withdrawal, form part of the Human Behavioural Pharmacotoxicology. 3. This ought to deserve greater attention on the part both of research workers and health authorities. PMID- 2896372 TI - Immunochemical characterisation of somatostatin in ruminants. AB - Following development and validation of a radioimmunoassay for somatostatin, the immunoreactivity of this peptide in the plasma of ruminants was measured and the levels in sheep were 9-31 pM (mean 18 +/- 7 pM, n = 48), in lambs 10-54 pM (mean 25 +/- 10 pM, n = 18) and in calves 5-35 pM (mean 12 +/- 6 pM, n = 22). Somatostatin-like immunoreactivity was present in sheep in high concentrations in the antrum (2342 +/- 280 pmol/g wet weight), duodenum (446 +/- 73 pmol/g) and pancreas (832 +/- 208 pmol/g). Lower concentrations (6-150 pmol/g) were found in other regions of the gastrointestinal tract. Molecular sieve chromatography on Bio-Gel P-10 showed that while most of the somatostatin in the antrum was somatostatin-14, in the duodenum about 30% of the total immunoreactivity was somatostatin-28. PMID- 2896373 TI - A comparison of the effects of vasoactive intestinal polypeptide on secretion from the submaxillary gland of the sheep and pig. AB - The effects, on secretion of fluid and protein from the submaxillary gland of intracarotid injections of acetylcholine or vasoactive intestinal polypeptide (VIP), and intracarotid infusions of VIP during a background of muscarinic stimulation, were examined in sheep and pigs. Intracarotid injections of VIP produced secretion of saliva from the ovine gland which continued after administration of atropine, phentolamine and propranolol. The protein concentration of this saliva was over 5-fold greater than that secreted in response to acetylcholine. Intracarotid injection of VIP did not evoke secretion from the porcine submaxillary gland but increased 3-fold the protein concentration in saliva evoked by subsequent intracarotid injection of acetylcholine. Intracarotid infusions of VIP in sheep produced dose-related increases in both flow (up to 1.9-fold) and protein concentration (up to 42-fold) of submaxillary saliva secreted in response to a background infusion of bethanechol. In pigs, intracarotid infusions of VIP at 0.015, 0.15 and 1.5 nmol/min produced increases in both flow and protein concentration of bethanechol evoked saliva. The increases in protein concentration (up to 2.8-fold) were dose related, but the increases in flow were not, being ca. 25% with each dose of VIP. The experiments provide evidence that VIP may effect mobilization of protein into saliva even in a species (pig) in which VIP does not evoke secretion of fluid. PMID- 2896374 TI - Molecular markers for linkage of genetic loci contributing to alcoholism. AB - Specific locus and random locus linkage approaches to identify markers for genes whose allelic variants predispose to alcoholism or for genes controlling relevant physiological and behavioral phenotypes are discussed. Sib-pair analysis is superior for the direct analysis of complex genetic traits such as alcoholism, but classic family analysis will be useful for transmission and linkage analysis for marker traits whose genetics is less complex. In mice, a large number of inbred strains, recombinant inbred and congenic strains, and specifically selected outbred strains are available. In the human, an intriguing linkage result has emerged between a brain protein variant and alcoholism accompanied by suicide. In the mouse, preliminary linkages have been established to loci controlling ethanol preference and also activation after ethanol. Large panels of random DNA and protein genetic probes and of probes for specific loci will in the future increase the probability of establishing linkage in both species. PMID- 2896375 TI - [Effect of somatostatin on exocrine pancreas function stimulated by cholecystokinin in the dog]. PMID- 2896376 TI - Diet composition and the plasma levels of some peptides regulating pancreatic secretion in the pig. AB - The aim of the present work was to study the effect of a modification of diet composition upon the plasma levels of some peptides known to be involved in the hormonal regulation of exocrine pancreas secretion. Six growing Large-White pigs weighing 41 +/- 3.2 kg were fitted with a catheter in a carotid artery; four of these pigs were also fitted with permanent fistulae in the pancreatic duct and duodenum. All the pigs were adapted to a control diet (C) during an 8-day period before surgery. In the 8-day postoperative period and a first experimental period of 4 days, they were fed on the same control diet. Three pigs were then fed the experimental diets in the following sequence: fat-rich diet (F) for 7 days, control diet (C) for 7 days, starch-rich diet (S) for 7 days, whereas the other three pigs were fed the same diets over the same time lengths but in inverse sequence: diet S, diet C, diet F. The three diets were isoproteinic (16% protein) and isocaloric (3,850 cal/kg). The pancreatic secretion and the plasma levels of cholecystokinin (CCK), secretin, pancreatic polypeptide (PP) and somatostatin were analysed during the 4 days of the first experimental period and the last day of each of the other three experimental periods. Total proteins and lipase and amylase activities were determined in pancreatic juice samples collected over the 7 hours following the morning meal. Arterial blood was sampled at 9 h 00 (before meal consumption), 9 h 30, 10 h 00 and every hour until 16 h 00. The results confirm pancreatic adaptation to the diet, i.e. increase of lipase specific activity (x 1.8) when the pigs ingested 6 times more fat (diet S----diet F) per day, and an increase in amylase specific activity (x 2.3) when they ingested 3 times more starch (diet F----diet S) per day. Furthermore, changes in diet composition did not lead to any durable, significant change in plasma peptide levels. In conclusion, CCK, secretin, PP and somatostatin, known to regulate exocrine pancreas secretion, would not be involved in the mechanisms of pancreatic amylase and lipase adaptation to the amount of carbohydrate and fat ingested by pigs. PMID- 2896377 TI - Structure specificities of yohimbine and indoloquinolizidine derivatives in blocking alpha-adrenoceptor and calcium channel. AB - 1,12b-Cis-1-p-nitrobenzoyloxyindoloquinolizidine as well as 14 beta-p nitrobenzoyloxyyohimbine possessed potent calcium channel blocking activities in the isolated rat perfused mesenteric vascular bed. Introduction of the bulky substituents to C-14 of yohimbine or to C-1 of indoloquinolizidine resulted in enhancement of the calcium channel blocking activities. By comparison of chemical structures between yohimbine and indoloquinolizidine, it was found that the E ring of yohimbine had no association with the calcium channel blocking activities. On the other hand, alpha 1- and alpha 2-adrenoceptor antagonistic activities which were tested in the rat mesenteric vascular bed and in the rat vas deferens, respectively, were markedly reduced by such introduction of the bulky substituents to yohimbine and indoloquinolizidine. From these results, it is expected that chemical modifications of indoloquinolizidine at the C-1 position provide new types of agents with calcium channel blocking activities. PMID- 2896378 TI - [Apudomas]. PMID- 2896379 TI - [Pharmacological treatment of anxiety]. PMID- 2896381 TI - Biochemical and immunologic diagnosis of cancer. Genetic markers. PMID- 2896380 TI - Distribution of choline acetyltransferase immunoreactive somata in the feline brainstem: implications for REM sleep generation. AB - In the present study we examined the distribution of cholinergic and catecholaminergic neurons, in the feline brainstem, as defined by choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) immunohistochemistry. In the dorsal tegmentum, ChAT immunoreactive neurons were distributed in the parabrachial area [the pedunculopontine group (PPG)] and along the medial adjacent central gray [the lateral dorsal tegmental group (LDT)]. The cholinergic neurons in the LDT area were larger than those in the PPG. When adjacent tissue sections were labeled with TH we noted extensive overlap between catecholamine and cholinergic neurons in the PPG, suggesting that REM sleep may occur as a result of an interaction between these transmitters in this area rather than the medial pontine reticular formation where no cholinergic or catecholamine neurons were found. Cholinergic neurons were also found in the cranial nerve nuclei and the nucleus ambiguus. The presence of cholinergic neurons in the PPG and LDT suggest that these neurons may play an important role in the generation of some of the tonic and phasic components of REM sleep, such as cortical desynchronization, pontogeniculo occipital waves, and muscle atonia. PMID- 2896382 TI - Immunohistochemical localization of yolk sac antigen 1 on rat spermatogenic cells. AB - The reactivity of monoclonal antibody (6D1, mAb) directed against yolk sac antigen 1 was verified on testes of young and adult rats. The antigen defined by 6D1 mAb was detected on the earliest appearing pachytene spermatocytes in the testis of 18-day-old rats. In the testis of the adult rat, the mAb reacted with pachytene spermatocytes, spermatids and spermatozoa. Less differentiated cells of spermatogenesis, for example spermatogonia and early spermatocytes, showed no reaction with the 6D1. Only after breaking down the blood-testis barrier, could the mAb injected intravenously reach the spermatogenic cells of the adluminar compartment in the seminiferous tubules. PMID- 2896383 TI - A multicentre comparison of trimoprostil and cimetidine in the treatment of duodenal ulcer. U.K. Trimoprostil Study Collaborative Group. AB - Trimoprostil is a new synthetic prostaglandin E2 analogue that inhibits acid secretion and has mucosal protective properties. It was compared with cimetidine to assess its effectiveness in the short-term treatment of duodenal ulcer. Seven centres recruited 107 patients, who were randomized to receive either 3 mg trimoprostil daily (n = 54) or 1 g cimetidine daily (n = 53) for 4 weeks, the drugs being taken in four divided doses. Of patients completing treatment, 23 of 40 (58%) healed with trimoprostil, compared with 47 of 53 (89%) with cimetidine (p less than 0.001). Both drugs relieved daytime and nighttime pain, but cimetidine was significantly quicker. Eight patients taking trimoprostil were withdrawn because of pain, nausea, and vomiting, but none taking cimetidine; diarrhoea did not occur with trimoprostil. There were no clinically significant changes in haematology or in biochemistry studies. In conclusion, trimoprostil was not as effective as cimetidine in the treatment of duodenal ulcer. PMID- 2896384 TI - Repopulation potential of thymocytes forming rosettes with phagocytic cells of the thymic reticulum. AB - Thymocytes binding in vitro to phagocytic cells of the thymic reticulum (P-TR), termed 'rosetting thymocytes', were injected intravenously into irradiated congenic mice and their migration patterns were compared with those that do not bind to P-TR, called 'non-rosetting thymocytes', similarly transferred. Donor cells, C57BL/Ka Thy 1.2, were distinguished from recipient cells, C57BL/Ka Thy 1.1 by a direct immunofluorescence technique using an anti-Thy 1.2 monoclonal antibody. The results demonstrate that the rosetting thymocytes have a greater capacity for homing back to the thymus and for populating the mesenteric lymph node and the spleen. Intrathymic transfer assay revealed that the donor-derived cells detected in the peripheral organs were of thymic origin. PMID- 2896385 TI - Expression of the T cell gamma gene by a functionally defined human T cell clone. Characterization at DNA, RNA, and cell membrane level. AB - In the present study we describe one CD2+CD3+ clone termed DS6 which expressed neither CD4 nor CD8 differentiation antigens and failed to react with WT31, a monoclonal antibody directed against the T cell antigen receptor alpha/beta heterodimer. This clone was isolated from peripheral blood T lymphocytes of a patient with a prolonged immunodeficiency after allogeneic bone marrow transplantation. Normal-sized T cell gamma gene transcripts were detected in DS6 by northern analysis, whereas no mature beta or alpha chain mRNA were found. The rearrangement of TCR beta chain genes and T cell gamma genes was analysed. While in DS6, TCR beta chain genes remain in germinal configuration, and a unique pattern of monoallelic T cell gamma gene rearrangement was observed. The rearrangement involves the recently described V gamma 5 segment and the J gamma 1 joining segment, which is located upstream of the C gamma 1 constant region. To determine the molecular structure present on DS6, an immunoprecipitation was performed with monoclonal anti-CD3 antibody and a rabbit antiserum raised against gamma protein. We have observed, in association with the CD3 complex, a 90 kDa structure which under reducing conditions resolves into three subunits of 45, 40 and 37 kDa. We demonstrated that the rabbit anti-gamma serum only immunoprecipitates the two lower bands. The upper band corresponds to a presently undefined T cell receptor chain. Next, we showed the non major histocompatibility complex (MHC)-restricted cytolytic activity exhibited by these CD3+CD4-CD8- cloned T cells and inhibition of the natural killer (NK)-like activity by the anti-CD3 monoclonal antibody. The triggering of CD2 or CD3 molecules increased IL 2 receptor expression on DS6 but failed to induce cell proliferation. This contrasts with recent results obtained with gamma-expressing T cell clones and illustrates the functional heterogeneity of the cells bearing the second T cell receptor. PMID- 2896386 TI - Seroprevalence and epidemiological correlates of HTLV-I infection in U.S. blood donors. AB - Screening for human T-lymphotropic virus type I (HTLV-I) antibodies was performed on sera from 39,898 blood donors at eight blood centers in geographically distinct areas of the United States. Ten donors (0.025 percent) showed evidence of HTLV-I seropositivity by enzyme immunoassays; this was confirmed by protein immunoblot and radioimmunoprecipitation. Seroprevalence rates ranged from 0 to 0.10 percent at the locations sampled, with HTLV-I antibodies found predominantly in donors from the southeastern and southwestern United States. Matched case control interviews and laboratory studies were performed on five seropositive women and two seropositive men who participated in an identity-linked collection of sera from a subset of 33,893 donors at six of the eight blood centers. Four of the women and both men are black; one woman is Caucasian. Four of the seven seropositive individuals admitted to prior intravenous drug abuse or sexual contact with an intravenous drug user. Sexual contact with native inhabitants of an HTLV-I endemic area was the only identified risk factor for one male. The distribution of HTLV-I antibodies in this U.S. blood donor sample corroborates the previously reported epidemiology of this agent and suggests that additional donor screening measures, including the testing of donated blood for HTLV-I markers, may be necessary to prevent the spread of HTLV-I to transfusion recipients. PMID- 2896387 TI - ADP-ribosyltransferase activity of pertussis toxin and immunomodulation by Bordetella pertussis. AB - Pertussis toxin is produced by the causative agent of whooping cough, Bordetella pertussis, and is an adenosine diphosphate (ADP)-ribosyltransferase capable of covalently modifying and thereby inactivating many eukaryotic G proteins involved in cellular metabolism. The toxin is a principal determinant of virulence in whooping cough and is a primary candidate for an acellular pertussis vaccine, yet it is unclear whether the ADP-ribosyltransferase activity is required for both pathogenic and immunoprotective activities. A B. pertussis strain that produced an assembled pertussis holotoxin with only 1 percent of the ADP ribosyltransferase activity of the native toxin was constructed and was found to be deficient in pathogenic activities associated with B. pertussis including induction of leukocytosis, potentiation of anaphylaxis, and stimulation of histamine sensitivity. Moreover, this mutant strain failed to function as an adjuvant and was less effective in protecting mice from intracerebral challenge infection. These data suggest that the ADP-ribosyltransferase activity is necessary for both pathogenicity and optimum immunoprotection. These findings bear directly on the design of a nontoxic pertussis vaccine. PMID- 2896388 TI - Translocation and rearrangement of myeloperoxidase gene in acute promyelocytic leukemia. AB - Acute promyelocytic leukemia (subtype M3) is characterized by malignant promyelocytes exhibiting an abundance of abnormally large or aberrant primary granules. Myeloperoxidase (MPO) activity of these azurophilic granules, as assessed by cytochemical staining, is unusually intense. In addition, M3 is universally associated with a chromosomal translocation, t(15;17)(q22;q11.2). In this report, the MPO gene was localized to human chromosome 17 (q12-q21), the region of the breakpoint on chromosome 17 in the t(15;17), by somatic cell hybrid analysis and in situ chromosomal hybridization. By means of MPO complementary DNA clones for in situ hybridization and Southern blot analysis, the effect of this specific translocation on the MPO gene was examined. In all cases of M3 examined, MPO is translocated to chromosome 15. Genomic blot analyses indicate rearrangement of MPO in leukemia cells of two of four cases examined. These findings suggest that MPO may be pivotal in the pathogenesis of acute promyelocytic leukemia. PMID- 2896389 TI - Guanylate cyclase and the adrenal natriuretic factor receptor. PMID- 2896391 TI - A longitudinal study of Japanese encephalitis in suburban Bangkok, Thailand. AB - A one-year study of Japanese encephalitis (JE) in a small focus of transmission was conducted in suburban Bangkok in 1985. Monthly data were collected on weather, vector density, sentinel pig and chick JE antibody seroconversions, and epidemiology as related to human JE cases. The primary vector species were found to be Culex gelidus and Culex tritaeniorhynchus; from which one isolate each was obtained in March and June, respectively. Pig JE antibody seroconversion peaked in April (the hottest month), with secondary peaks following in July and December. Chick seroconversions were found only in June and July. Human cases (7) in the primary focus occurred from May-July, and started 2 months following the finding of the first JEV isolate in mosquitoes and 1 month following mass JEV seroconversion in pigs. Overall, the attack rate in the focus (0.83/10(5] was greater than 4 times that of the rest of Bangkok (0.19/10(5]. Attack rates were highest in 0-9 and 10-19 year-old groups, respectively. Indications are that JEV is transmitted to humans in Bangkok at least 10 out of 12 months per year, but that cases are concentrated in the May to July period. PMID- 2896390 TI - A high incidence of neurological complications following Semple anti-rabies vaccine. AB - A study was conducted to determine the incidence of neurological complications among a cohort of 6,980 recipients of Semple vaccine administered in Bangkok and 5 nearby provinces in 1984. A review of all patients admitted to public hospitals in these 6 provinces discovered a total of 32 cases, with neurological complications following Semple vaccine. Twenty-two cases (68.8%) were encephalitis or myelitis. The complication rate was 3.6 times higher for males than females and the rate was lowest in the 0-14 year age group. Vaccinees receiving large daily dose of vaccine had a higher rate of complications than those with low dose regimen. One patient died, giving the case-fatality rate of 3.13 per cent. Since the search was limited, the rate of neurological complications to Semple vaccine was a minimum of 4.6 cases per 1,000 vaccinees [1:220]. This complication rate was much higher than most rates reported previously. It is imperative to find economically feasible alternatives to Semple vaccine. PMID- 2896392 TI - [Norcuron--vecuronium, a muscle relaxant for cholecystectomy]. PMID- 2896393 TI - Prevention and treatment of urinary retention and infection after surgical treatment of the colon and rectum with alpha adrenergic blockers. AB - In a retrospective study, 153 male patients who underwent surgical treatment of the colon and rectum presented with complaints indicating obstruction of the prostate gland and clear indications for preoperative administration of alpha blockers. Between the years 1982 and 1984, the alpha-blocker phenoxybenzamine hydrochloride (PB-HCl) was prohibited from use by the Ministry of Health because of suspicions of its carcinogenic properties. This enabled a comparative study between two groups of patients. Seventy-five patients (group 2a1) were prohibited from receiving PB-HCl. Urinary retention occurred in 54.7 per cent and urinary tract infection in 65.3 per cent. Seventy-eight patients (group 2a2) were administered PB-HCl. In this group of patients, urinary retention occurred in 19.2 per cent and urinary tract infection in 15.4 per cent. Forty-one patients with urinary retention of group 2a1 who were not administered PB-HCl were compared with 50 patients with urinary retention (group 3) who received PB-HCl. Spontaneous relief was observed in 21.9 and 76.0 per cent, respectively. PB-HCl was shown to be extremely effective, both as a preventative and therapeutic agent, when complaints indicating the prostate gland are present in patients undergoing surgical treatment of the colon and rectum. PMID- 2896394 TI - Metabolic intervention in surgical patients: the effect of alpha- or beta blockade on glucose and protein metabolism in surgical patients receiving total parenteral nutrition. AB - We performed a series of isotopic studies on the role of alpha- or beta adrenergic activity in the regulation of glucose and protein metabolism in a group of surgical patients receiving total parenteral nutrition. We quantitated rates of glucose turnover and net protein breakdown by the primed constant infusion of 3H-glucose and 14C-urea, respectively. Basal measurements were first performed, and then the effect of either alpha- or beta-adrenergic blockade was assessed by means of the constant infusion of either phentolamine or propranolol. In addition, we assessed the effect of beta-stimulation by infusing the beta agonist, salbutamol. The institution of alpha-adrenergic blockade did not significantly alter either the plasma glucose level or the rate of glucose production. However, the rate of net protein catabolism decreased significantly after alpha-adrenergic blockade. Before alpha-blockade the value for NPC was 0.88 +/- 0.27 gm/kg/day, and after alpha-blockade the corresponding value was 0.73 +/- 0.24 gm/kg/day (p less than 0.01). beta-Adrenergic blockade resulted in a decrease in the rate of glucose appearance from 38.2 +/- 6.1 mumol/kg/min to 35.1 +/- 5.7 mumol/kg/min, and the plasma glucose clearance increased from 5.0 +/- 0.8 ml/kg/min to 5.4 +/- 0.8 ml/kg/min. As a result of these changes the plasma glucose concentration decreased significantly (p less than 0.01) from 7.4 +/- 0.3 mumol/ml to 6.5 +/- 0.5 mumol/ml. beta-Adrenergic blockade did not significantly decrease the rate of net protein catabolism. beta-Stimulation with salbutamol resulted in a significant increase (p less than 0.05) in the rate of glucose production from 31.3 +/- 4.2 mumol/kg/min to 38.0 +/- 6.5 mumol/kg/min, and as a result the plasma glucose level increased significantly from 6.7 +/- 0.6 mumol/ml to 7.4 +/- 0.6 mumol/ml (p less than 0.04). We conclude from these studies that the role of the adrenergic nervous system in the promotion of endogenous glucose turnover in surgical patients receiving total parenteral nutrition is primarily a beta-adrenergic effect, whereas the promotion of protein catabolism is mainly an alpha-adrenergic effect. PMID- 2896395 TI - Morphologic effects of orchiopexy or orchiectomy on the contralateral testis in experimental unilateral cryptorchidism. AB - For evaluation of the effects of orchiopexy and orchiectomy on the contralateral descended testis, unilateral cryptorchidism was produced in 60 21-day-old mice by suturing of the left testis to the inner abdominal wall. A sham operation was performed on the left testis of 20 control mice (S). After creation of unilateral cryptorchidism, orchiopexy (P) or orchiectomy (O) was performed on the left testis at 2 (group I) and 10 (group II) weeks (ten mice each). All testes were removed for examination 2 weeks after orchiopexy or orchiectomy. In both groups the mean values of testicular weight, seminiferous tubular diameter, and tubular biopsy score of contralateral O testes were always statistically similar to the values of contralateral S testes (p greater than 0.01). The difference between TBS values of contralateral P and S testes was not significant in group I (p greater than 0.01), but it was significant in group II (p less than 0.01). The data from this murine experiment suggest that orchiectomy for unilateral cryptorchid testis is almost always helpful in improving contralateral morphology; however, orchiopexy can be helpful if it is not performed late in the period of maturation. PMID- 2896396 TI - Genotype assignment of haemophilia A: an extra polymorphic Taq I site in the St14 (DXS52) locus might lead to faulty conclusions. PMID- 2896398 TI - [Somatostatin. Physiology, physiopathology and therapeutic use]. PMID- 2896397 TI - Human platelet activation by bacterial phospholipase C: mechanism of inhibition by flurazepam. AB - We have shown earlier that phospholipase C (PLC) from Clostridium perfringens causes platelet activation possibly by inducing turnover of phosphoinositides and phosphorylation of a 47,000 Dalton protein (P47). Moreover, only 15 microM and 11 microM flurazepam inhibits PLC-induced platelet aggregation and serotonin secretion by 50% respectively. This study was conducted to better understand the mechanism of platelet activation by PLC and its inhibition by flurazepam. Incubation of (14C)-arachidonic acid labelled platelets with PLC produced diacylglycerol in a time- and concentration-dependent manner. Flurazepam did not inhibit diacylglycerol production by PLC. Paranitrophenolphosphorylcholine and prostaglandin E1 inhibited diacylglycerol production by 75% and 20% respectively. In a platelet-free system PLC hydrolyzed 14C-choline-phosphatidylcholine (14C-PC) in a time- and calcium ions-dependent manner. Flurazepam had no effect on PLC induced hydrolysis of 14C-PC. Platelet cytosolic fraction (PCF), containing phosphatidylinositol-specific PLC (PI-PLC), hydrolyzed (3H-inositol) phosphatidylinositol (3H-PI) in a platelet-free system. Flurazepam did not inhibit hydrolysis of 3H-PI by PCF. Phospholipase C caused phosphorylation of P47 in 32P-labelled platelets. Flurazepam did not block phosphorylation of P47 in the first three minutes and had very little inhibitory effect by five minutes. However, flurazepam completely blocked phosphorylation of P47 by seven minutes. Platelet aggregation induced by ionomycin, a calcium ionophore, was completely inhibited by 100 microM flurazepam whereas platelet aggregation induced by 12-O Tetradecanoylphorbol-13-acetate (TPA), which mimics the action of diacylglycerol, was partially inhibited by 300 microM flurazepam. These findings suggest that PLC induced platelet activation depends, at least in part, on diacylglycerol production and phosphorylation of P47. These data also suggest that flurazepam does not inhibit PLC-induced platelet activation by inhibiting: (a) the production of diacylglycerol from phosphatidylcholine; and (b) the action of PI PLC on phosphatidylinositol. The ability of flurazepam to inhibit ionomycin induced platelet aggregation indicates that flurazepam is able to block platelet activation by inhibiting the increase in free cytosolic calcium ions in platelets or by inhibiting a step subsequent to the rise in intraplatelet calcium ions. PMID- 2896399 TI - Significant envenomation by Aurelia aurita, the moon jellyfish. AB - The case of a patient envenomated by Aurelia aurita, who developed significant local cutaneous lesions and immunospecific serum antibodies is reported. The lesions required more than ten days to heal. The patient developed significant cross-reacting antibodies to Chrysaora quinquecirrha antigens. PMID- 2896400 TI - [Acute dental trauma in children (a structural statistical analysis)]. PMID- 2896401 TI - Multicenter trial of hemodilution in acute ischemic stroke. Results of subgroup analyses. Scandinavian Stroke Study Group. AB - In a multicenter trial, 183 patients with acute ischemic stroke of less than 48 hours' duration and hematocrits of 38-50% were randomized to standardized hemodilution treatment (venesection and dextran 40 administration) and 190 to a control group. We have previously reported that there were no beneficial effects of hemodilution in the total patient population. In this report, the case fatality rates and neurologic outcome in survivors (3 months' follow-up) in subsets of patients have been analyzed. The patients were subgrouped by sex, age, medical history, smoking habits, delay from the onset of symptoms to the start of treatment, hematocrit at entry, venesection volume, neurologic score at entry into the study, blood pressure changes in the acute phase, presence of atrial fibrillation, location of brain lesion by computed tomography, type of diagnostic procedures, and hospital setting. No subset in which hemodilution reduced mortality or improved neurologic outcome could be identified. Case fatality rate was apparently higher in hemodiluted patients with infarction affecting deep brain structures than in control patients with such lesions. By simple clinical criteria, we have been unable to define subsets of stroke patients who benefit from the present standardized regimen of moderate hemodilution. The sample sizes are, however, too small to refute the possibility that a modest clinical effect of hemodilution may be present in some patients with stroke. PMID- 2896402 TI - The Dutch TIA trial: protective effects of low-dose aspirin and atenolol in patients with transient ischemic attacks or nondisabling stroke. The Dutch TIA Study Group. AB - We describe the background, design, and organization of a double-blind clinical trial in patients with transient ischemic attacks or nondisabling stroke in more than 60 hospitals in The Netherlands. Two different therapeutic comparisons are made by double randomization: 30 mg vs. 300 mg acetylsalicylic acid, and 50 mg atenolol vs. placebo. For the diagnosis, a checklist has been used on which the time course and the nature of the symptoms are recorded in plain language. The analysis will primarily assess death and disability from all causes, with disability measured using a modified Rankin scale. Secondary end points will be vascular death, nonfatal stroke, nonfatal myocardial infarction, and retinal infarction. The study will last for a minimum of 3 years and should involve at least 2,500 patients. More than 1,100 patients were randomized in the 1st year. PMID- 2896403 TI - [Beta-adrenoblockers studied on a thin layer of sorbent]. PMID- 2896404 TI - Increased frequency of CD8+CD11+ cells expressing the T cell receptor in long term allograft recipients. PMID- 2896406 TI - [Betaxolol. A new beta blockader with beta-1-selectivity in glaucoma treatment]. PMID- 2896405 TI - Rifampicin reduces nephrotoxicity of cyclosporine A in rats: studies of renal enzyme excretion. PMID- 2896407 TI - [Morphologic examination of the urothelium after irradiation with laser energy]. AB - The energy of a Nd-YAG laser (1,064 nm wave length, 8 ns pulse duration) was used to irradiate the urothelium of the ureter or bladder and kidney parenchyma in pigs. Single pulse energy was 50-120 mJ with a 20-Hz repetition rate. The horizontal laser beam was reflected 90 degrees down by a 100% mirror and with a specially designed apparatus focussed on the surface of the tissue. Laser light from a quartz glass fiber was also focussed directly onto the tissue. Urothelium and kidney parenchyma were irradiated in 7 pigs. Tissue samples were examined histologically and raster electron microscopically 2, 4, 8 and 12 days after irradiation. No macroscopic lesion could be found. Maximum energy caused a small cone of 40 micron depth. No thermic effects or necrosis resulted, so that no harm is to be expected with unintentional irradiation. PMID- 2896408 TI - Changing pattern of scrotal exploration for testicular torsion. AB - A total of 201 urgent scrotal explorations for unilateral painful testis was performed over a six-year period. Seventy-two (36%) testicular torsions were identified. Fifty-seven (79%) testes were salvaged and fifteen (21%) orchiectomies were done. Although the annual number of scrotal explorations increased over the years of study, no benefit in terms of increased testicular salvage could be identified. PMID- 2896409 TI - Presence of pili in Pasteurella multocida strains associated with atrophic rhinitis. PMID- 2896410 TI - Idazoxan and blood gas changes. PMID- 2896411 TI - [Effect of the intake of different doses of trace elements and their combination with other biologically active substances on iron, copper and manganese metabolism in highly qualified athletes]. AB - Investigations conducted on athletes have shown that combinations of trace elements (Fe, Cu and Mn) in biotic doses with vitamins, glutamic acid or dibasol produce a favourable effect on trace element metabolism, and on the body functions. Enrichment of food rations with vitamins only, using no trace elements, drastically increased the secretion of Fe, Cu and Mn from the body. High doses of Fe-containing drugs disturbed Mn balance. PMID- 2896412 TI - Blurred vision and headaches in a patient positive for HBsAg. PMID- 2896413 TI - [A model of early visual deprivation as a reflection of the patterns of functionally induced biochemical heterogeneity of neurons]. PMID- 2896414 TI - [Neuromediator shifts in the peripheral blood of dogs resulting from negative emotiogenic exposure]. AB - The analysis of negative emotiogenic influence in dogs carried out according to dynamics of levels of acetylcholine and catecholamine content in peripheral blood and concomitant changes of the higher nervous activity, allows to conclude about the participation of both cholinergic and catecholaminergic neurotransmitter systems in reactions to this influence with a relative predominance of the first one. In animals with decreased reactivity and with compensatory abilities of the cholinergic system, the same influence leads to enhancement of the specific significance of the reaction of the catecholaminergic system, and especially of its transmitter, noradrenergic component. PMID- 2896415 TI - [Is Moraxella pathogenic? The problem and its possible solutions]. PMID- 2896416 TI - [Effect of aceclidine and fenazepam on the indices of humoral immunity and nonspecific resistance of the body after immunization with a chemical typhoid vaccine]. AB - Phenazepam (2.5 mg/kg) and aceclidine (4 mg/kg), when introduced in a single injection at the inductive phase of immune response, enhance the production of antibodies after immunization with chemical typhoid vaccine. The combined use of these preparations has been to produce a potentiating effect. PMID- 2896417 TI - [Use of the coagglutination reaction of yeast-like Candida maltosa fungi for detecting fimbriae in intestinal bacteria]. AB - The capacity of nonpathogenic yeast-like C. maltosa strains to coagglutinate Escherichia coli has been studied. C. maltosa cells have also been shown to coagglutinate E. coli possessing mannose-sensitive adhesins in a wide range of their concentrations (5-140 bacterial cells per C. maltosa cell). Strains belonging to types CFA/I and CFA/II with fimbriae, similarly to their corresponding paired genetically related strains without these adhesins, are practically incapable of agglutinating C. maltosa cells, while strains K88 and B41 react with them. The reaction occurs at a concentration of 9.5-37.0 and 38.0 55.5 bacteria respectively per C. maltosa cell and is not inhibited by 1% d mannose. The suggestion that C. maltosa cell surface glycoproteins contain not only receptors for E. coli fimbriae, type I, but also components similar in their structure to receptors specific to the mannose-resistant adhesins of strains K88, K99 and 41, has been confirmed by hemagglutination inhibition with C. maltosa surface antigens as inhibiting agents. PMID- 2896418 TI - Excitable membranes--object for evaluating the effect of heavy metal pollution. AB - In acute experiments the interaction of heavy metals (CdCl2 and HgCl2) with neurotransmitters (ACh and 5HT) was studied on the excitable membrane of the identified neurons in the central nervous system of Helix pomatia L. (Gastropoda, Mollusca). It was shown that cadmium and mercury ions exert different influence on both resting and action potentials as well as on the responsiveness of the neural membranes to ACh and 5HT. The selective blocking effect of cadmium and mercury ions can be interpreted on the basis of specificity of postsynaptic receptor structures responsible for the transmitter action and of ion-channels involved in the excitatory processes. The heavy metal effect was not uniform for the different types of neurons, suggesting that pollutants can modify various functions to a different degree. The results show that testing on nerve cell membranes can serve as a useful method and model in investigating the effect of sublethal environmental contamination, as they may cause a profound modulation on the elements of the neural circuitry responsible for the regulation of the animal's behavior. PMID- 2896419 TI - [Epidemiological study of human T-cell leukemia virus type I infection in healthy residents and patients with non-hematologic diseases in the Kagoshima district]. PMID- 2896421 TI - [Studies on hypercalcemia associated with adult T-cell leukemia-lymphoma]. PMID- 2896420 TI - [Detection of adult T-cell leukemia-associated antigen (ATLA) and anti-ATLA antibody (anti-ATLA) in patients with hematologic malignancies in the Kagoshima district]. PMID- 2896422 TI - Thoracic epidural anesthesia in conscious and anaesthetized rats. Effects on central haemodynamics compared to cardiac beta adrenoceptor and ganglionic blockade. AB - A simple technique for cannulation of the thoracic epidural space in rats was described. 40-50 microliter of epidural bupivacaine 5 mg/ml induced a distribution of sensory analgesia from lower cervical to lower thoracic segments. With this model, effects of thoracic epidural anaesthesia (TEA) on mean arterial pressure (MAP), cardiac output (CO), systemic vascular resistance (SVR), stroke volume (SV), heart rate (HR), central venous pressure (CVP), left ventricular end diastolic pressure (LVEDP) and maximal increase of pressure in the left ventricle (max dp/dt) were studied in six groups of animals: 1) In conscious animals (n = 10) MAP, CO, SV and HR decreased significantly by 12%, 25%, 10% and 16%, respectively, while SVR increased significantly by 20% during TEA; 2) In chloralose-anaesthetized animals (n = 7) the reduction in CO during TEA was less pronounced and there were no significant changes in SV or SVR; 3) In conscious animals (n = 6) LVEDP, CVP and max dp/dt decreased significantly during TEA; 4) Hexamethonium, when administered to pharmacologically vagotomized conscious animals during TEA (n = 8), induced a significant decrease in SVR (23%) but no change in HR; 5) Changes in haemodynamics after cardiac adrenoceptor blockade with metoprolol, in conscious animals (n = 12), did not differ significantly from those seen during TEA, except for an unchanged SV after metoprolol; 6) 50 microliters of bupivacaine (5 mg/ml) when given i.v. to conscious animals (n = 8) did not affect CO, SV, HR or TPR significantly, while MAP increased slightly but significantly. Thus, in this conscious animal model, TEA almost completely and rather selectively blocked probably mediated by a reflex activation of unblocked sympathetic efferents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896423 TI - Epidural sufentanil for intra- and postoperative analgesia in thoracic surgery: a comparative study with intravenous sufentanil. AB - A comparative study was undertaken to evaluate the effectiveness of epidural sufentanil in providing intra- and postoperative analgesia during thoracic surgery. Sufentanil was chosen on the basis of its high lipid solubility and its potent opiate receptor binding. Epidural sufentanil was compared with intravenous sufentanil as the major intraoperative analgetic agent in an anesthesia regimen with midazolam and nitrous oxide. Epidural sufentanil significantly decreased the need for supplementary intravenous analgesia. In the epidural sufentanil group the immediate postoperative analgesia was found to be better, with a longer duration of action, compared with the intravenous sufentanil group. Postoperatively epidural sufentanil was compared with epidural morphine. Sufentanil provided good analgesia with a very fast onset and a mean duration of almost 7 h. Severe respiratory depression was observed in one patient within 1 h of extubation, probably due to the combined effects of the narcotic administration and residual midazolam. It is concluded that 50 micrograms of sufentanil administered in the thoracic epidural space provides valuable intraoperative analgesia which can easily be extended into the postoperative period, although all necessary precautions for epidural opiate administration should be taken. PMID- 2896424 TI - Treatment of terminal cancer pain in Finland. A questionnaire survey. AB - A questionnaire concerning current practice in the treatment of cancer pain was sent to 783 Finnish physicians. This study is based on the replies from 421 physicians who stated that they at least sometimes see cancer patients. Three simulated patient cases were presented in the questionnaire, and the adequacy of the treatment suggestions was evaluated. The results indicated that drugs predominate in the treatment of cancer pain. The suggested doses of narcotic analgesics were well below the minimum effective daily doses. As many as half of the physicians failed to use the therapeutic modalities correctly, irrespective of the frequency of their seeing cancer patients. Education in effective pain treatment should therefore be intensified to ascertain that all physicians involved in clinical practice have satisfactory knowledge of the treatment of cancer pain. PMID- 2896426 TI - Massive hepatic infarction associated with polyarteritis nodosa. AB - A massive hepatic infarction was found in a 44-year-old man who had suffered from polyarteritis nodosa for two years. The polyarteritis had been well controlled by administration of corticosteroids, but he died due to an opportunistic fungal infection. At autopsy, a massive hepatic infarct and a fresh thrombus occluding the right portal vein trunk were found. In addition, occlusion of the heptic arterial branch with fibrosis and dissociation of elastic fibers due to polyarteritis was noted. Massive hepatic infarction is uncommon. The clinicopathologic features of this case are described, and the pathogenesis of hepatic infarcts is discussed. PMID- 2896425 TI - Effects of adrenergic drugs on accommodation and distant refraction in daylight and darkness. A laseroptometric study. AB - Near point accommodation was measured using a RAF near point rule, and distant refraction in daylight and darkness were determined using a laseroptometer in a double-blind cross-over study on 10 healthy test subjects (19-31 years). Determinations were made before and 40 min after topical instillations of 3 X 10 microliters 10% phenylephrine, 0.5% thymoxamine, 1% adrenaline, 3% isoproterenol, 0.5% timolol and 0.5% betaxolol. Combinations of 3 X 10 microliters 0.5% thymoxamine + 10% phenylephrine, 0.5% timolol + 1% adrenaline and 0.5% betaxolol + 3% isoproterenol were also administered. The near point of accommodation decreased 0.8 +/- 0.3 diopter after instillations of the alpha 1 adrenoceptor agonist phenylephrine, while an increase of 0.6 +/- 0.2 diopter was determined after administration of the alpha adrenoceptor antagonist thymoxamine. Thymoxamine plus phenylephrine did not alter the pretreatment values. Beta adrenoceptor stimulation by isoproterenol or beta adrenoceptor inhibition by timolol or betaxolol had no effect on the near point accommodation. The difference between distant refraction in daylight and darkness, that is low luminance myopia, amounted to -1.25 +/- 0.1 diopter. Phenylephrine caused a myopic shift in distant refraction in daylight and darkness of 0.32 +/- 0.1 and 0.9 +/- 0.2 diopter, respectively. This effect was due to the mydriatic action of phenylephrine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896427 TI - A study of nootropic drugs for anti-anxiety action. AB - The effects of adafenoxate (100 mg/kg), aniracetam (50 mg/kg), meclofenoxate (100 mg/kg), piracetam (250 mg/kg), and standardized ginseng extract-G115 (100 mg/kg) applied for five days were studied with Vogel's conflict procedure in which thirsty naive rats were periodically administered shocks for licking water. The results showed a significant anti-anxiety effect (increases in licking) with adafenoxate and meclofenoxate. Piracetam significantly suppressed licking behaviour and this effect was evaluated as anxiogenic (resulting from the non specific stimulant action of the drug). Adafenoxate was found to increase also the number of entries into and escapes from the dark compartment without punishment responding. This effect of adafenoxate was considered to be an expression of facilitated conditioned-reflex activity. A beneficial role for the observed anti-anxiety effects of adafenoxate and meclofenoxate in the nootropic action of these drugs is suggested. PMID- 2896428 TI - Behavioural and radioligand analysis of the effect of two new piperazine derivatives with anxiolytic properties. AB - The experiments were carried out on Wistar rats, using a conflict situation consisting in opposition of two motivations: positive (water drinking) and negative (electrical pain). Two newly-synthesized piperazine derivatives with proved psychotropic activity (4P-183 and GP4) were studied and compared with the classical benzodiazepine tranquilizing agent diazepam. Parallel with this, the affinity of these compounds to the benzodiazepine receptor in mouse brain was tested (radioligand binding of 3H-diazepam), as well as the changes in the characteristics of binding (dissociation constant and density of the receptors) after 14-day administration o doses equal to 1/3 LD50 of the two compounds. The results indicate the existence of anxiolytic (anticonflict) activity in both compounds. The fact that the above-mentioned derivatives do not interact with 3H diazepam (in vitro), changing above all the dissociation constant after chronic administration, suggests predominantly nonspecific type of binding to the receptors. It is possible that their anxiolytic activity is associated with indirect interactions with one of the components of the GABA-benzodiazepine receptor complex, similar to the atypical tranquillizers. PMID- 2896429 TI - Treatment of sex offenders with imaginal desensitization and/or medroxyprogesterone. AB - Thirty sex offenders were randomly allocated: 10 to receive medroxyprogesterone therapy (M), 10, imaginal desensitization (ID) and 10 both (ID + M). Twenty-four responded for one year though 3 subsequently relapsed. There were no significant differences in response to the 3 treatments. Four patients who did not respond to the initial treatment and the 3 who relapsed responded to further treatment. Most treated with M maintained heterosexual intercourse at pretreatment frequency. Self-reported reduction in anomalous sexual urges in patients receiving M correlated with reduced testosterone levels one month following treatment, demonstrating that the response was specific and validating the assessment by patients' self-reports. Where cost-effectiveness or time constraints are factors influencing treatment of sex offenders, one of these therapies warrants consideration. PMID- 2896430 TI - Psychiatrists and mental health in philately. AB - Can it be said that history's most outstanding psychiatrists and the various interrelated fields of mental health are to any extent realistically represented within the framework of thematic philately? With regard to the latter theme, five main categories can be distinguished: the mentally handicapped; psychiatric institutions, founders, nursing staff, etc.; prevention of alcohol and drug abuse; congresses and, finally, famous psychiatric patients. This article is a summary based on the brochure of the same name (32 pages in colour) published by CIBA-GEIGY B.V., Arnhem, The Netherlands. PMID- 2896431 TI - The effect of neuroleptics on prolactinoma growth in a Jordanian schizophrenic girl. AB - We describe a case of a schizophrenic girl who developed prolactinoma while being treated with neuroleptics. The clinical history and special investigations of the pituitary tumor suggest that neuroleptic medications may have enhanced the growth of the tumor in our patient. The author suggests that the relationship between the occurrence of prolactinoma and neuroleptic medications ought to be investigated in a large controlled study. PMID- 2896432 TI - [Post-traumatic pain syndromes of the shoulder joint--differentiation and treatment]. AB - The main symptom of posttraumatic trouble in the shoulder-joint is the painful immobility. We had to differentiate between genuine shoulder pain originating in shoulder alternation and shoulder pain in consequence of other diseases. Significant causes of posttraumatic shoulder pain are the impingement syndrome with tendon alteration or lesion or, due to fractures, the instable shoulder joint as well as shoulder rigidity. An exact diagnosis and, in consequence an exact treatment can only be accomplished basing on accurate history and specific clinical examination. PMID- 2896433 TI - [Kuntscher intramedullary nailing of the tibial shaft fracture. A 19-year evaluation]. AB - Marrow nailing developed by Gerhard Kuntscher for long tubular bones is an excellent surgical procedure for fractures of the lower leg shaft. It yields outstanding results both with the typical good indications in respect of shape of fracture, localisation and soft tissue conditions and even with atypical borderline and emergency indications where the healing results can be said to be good and satisfactory. Of course long-standing experience is required especially when employing the Kuntscher intramedullary nail in the atypical range of indications. This method produces good results even in critical situations if appropriate accompanying measures are taken. Technique, results and complications are described in this article reflecting the experience of 19 years of working with the intramedullary Kuntscher nail. PMID- 2896434 TI - [Complications following osteosynthesis management of femoral neck fractures with spongiosa locking screws]. AB - Osteosynthesis under pressure using two perforating cancellous bone screws in medial and lateral fractures of the neck of the femur and in some cases also in pertrochanteric fractures of the femur has proved successful, in our opinion, in surgery aimed at preserving the head of the femur, as has been confirmed at our hospital by follow-up studies. A striking fact that came to light during follow up was that there was a higher percentage of incidence of necroses of the femoral head following Pauwels-I-type fractures. However, in our case it was only one necrosis of the head of the femur in a total of five Pauwels-I-type fractures treated by osteosynthesis. A final judgment can surely be passed only by studying a larger number of cases for a longer period of time. We will, therefore, follow up the fractures of the neck of the femur a few years later by re-examination. As a matter of principle, the aim of surgery in osteosynthesis of a medial femoral neck fracture can be attained by means of the cancellous bone screws. A very important aspect which is most essential for successful surgery is the accurate and controlled introduction of the screws via the guide wire. The infection risk is reduced by the small operative approach. In view of the fact that the follow up examinations revealed more than 72% well-healed fractures of the neck of the femur, we do not think it necessary to effect any changes in our surgical procedure at the present time. PMID- 2896435 TI - [Technic and results of covered ankle joint arthrodesis with autocompression angle plates]. AB - In 1973, Mittelmeier introduced a new technique of arthrodesis of the ankle joint by internal osteosynthesis using an autocompression plate with additional compression screwing of fibula to tibia and talus in order to avoid the disadvantages of previous operative methods of arthrodesis by bone splinting or external fixation (longer cast immobilisation, handicap by external fixator, danger of bone hole osteomyelitis a.o.). Regarding this new technique, the fibula works as a petiolated well vascular bone chip which bridges the joint. Representation of the special operative technique of covered autocompression arthrodesis of the upper ankle joint rsp. - in case of special indication - the combined arthrodesis of the upper and lower ankle joint. Representation of our casuistry of 43 patients who underwent this operation. With the exception of one case (osteomyelitis recidivation with following pseudarthrosis) a fast bony consolidation of the arthrodesis was achieved. In the meantime the osteosynthesis material is removed in 35 cases. One third of the patients gets along with conventional shoes. PMID- 2896437 TI - [Treatment and results in severe craniocerebral trauma]. AB - Treatment of severe craniocerebral traumas in medium and major hospitals not provided with special neurosurgical equipment requires particularly close interdisciplinary cooperation between surgeons, neurologists and anaesthesiologists. CT facilities are an essential prerequisite for best possible patient care. Patient safety during the posttraumatic and postoperative phases is improved by measuring the intracranial pressure. Whereas corticosteroid treatment may be arguable, barbiturate treatment should presently not be a routine procedure because of its side effects and high rate of complications. PMID- 2896436 TI - [The cast walking shoe combined with modern synthetic support bandages]. AB - Rehabilitation with regard to mobility and function of immobilized lower extremities can be speeded up if the patient can move more frequently and freely with a loadbearing cast. This paper reports on the use of a new external cast system together with a cast shoe. Based on documented cases of empirical experience it is demonstrated that in many cases patients can return to work despite having to wear a cast. PMID- 2896439 TI - [Tenovaginitis stenosans in the area of the peroneal tendon]. PMID- 2896438 TI - [Changes in morbidity following traumatologically-induced splenectomy]. AB - 12 patients were followed up who had been splenectomised between 1978 and 1985 after traumatic injury of the spleen. Analysis of late morbidity after loss of the spleen was performed besides physical examination and a study of clinical pathology findings, the analysis being based on the individual anamnesis and history of previous diseases of each patient. It was not possible to establish a clear rise in general an infection-conditioned morbidity. We believe that the simple method of comparing preoperative and postoperative disease periods on the basis of the individual list of previous diseases represents a new objective parameter for assessing the late sequelae following splenectomy. PMID- 2896440 TI - [Surgical management of acromioclavicular joint separation with transcutaneous Kirschner wire fixation. Results of follow-up in 45 patients]. AB - 45 patients were followed up who had undergone surgery because of acromioclavicular separation of the types TOSSY II and TOSSY III during 1983 to 1985. In 44 cases a fresh acromioclavicular separation had been treated via transcutaneous Kirschner wire fixation and in one case a chronic acromioclavicular separation had been treated according to the technique described by Bunnell. the anatomy of the acromioclavicular joint, the pattern of injury as well as the method of surgery with subsequent aftercare measures are described. The good functional final results make transcutaneous Kirschner wire fixation the method of choice as a brief and low-stress procedure, as far as our clinic is concerned. PMID- 2896441 TI - Direct transmission of Trypanosoma cruzi between vectors of Chagas' disease. AB - Trypanosoma cruzi was transmitted directly between triatomines by cannibalism or coprophagy. Different conditions involving cannibalism that excluded coprophagy were studied in Dipetalogaster maximus. Infections occurred if an uninfected donor bug sucked infectious blood and if this blood was taken up from the stomach by a cannibalistic bug. If the donor was infected and sucked uninfected blood afterwards, the source of the uninfected blood determined the transmission rate: If the uninfected blood originated from mice, many cannibalistic bugs became infected because complement factors from mouse blood did not lyse T. cruzi in the stomach of the bug. If the uninfected bloodmeal originated from chickens, cannibalistic bugs occasionally became infected, even though chicken blood is known to lyse all stages of T. cruzi in the stomach. Experiments on coprophagy provided the first conclusive demonstration that transmission of T. cruzi occurs between individual Triatoma infestans, as a result of coprophagic behaviour alone, and excluding the possibility of cannibalistic transmission. PMID- 2896442 TI - Selection for drug resistance in Trypanosoma congolense during cyclic transmissions through Glossina morsitans morsitans and drug treated rabbits. AB - A drug-sensitive Trypanosoma congolense (IL 1180 strain), with a known CD50 and CD90 (doses required to cure 50 and 90% of the infected animals) was cyclically passaged through tsetse flies. The infected flies were then fed on rabbits which received weekly prophylactic treatment of Samorin. It was observed that the infections arising from flies maintained for over 60 days on drug-treated rabbits required higher curative doses to achieve a 50 and 90% cure. The results of this work suggest that a selection for drug resistance occurs when trypanosome stage in Glossina is continuously exposed to drug-treated animals. PMID- 2896443 TI - Nuclear DNA content of Trypanosoma congolense. AB - We have measured the nuclear DNA content of the major life cycle stages of Trypanosoma congolense, in two clones of geographically distant origin. We find that nuclear DNA content in epimastigote, mammalian blood-stream and metacyclic forms is constant and that the nuclear DNA contents of the two clones were 0.1 pg and 0.09 pg, respectively. PMID- 2896444 TI - Cultivation of the life cycle stages of Trypanosoma brucei sspp. AB - A culture system was devised for the production of the various stages in the developmental cycle of Trypanosoma brucei brucei and T. b. rhodesiense. The bloodstream forms were grown at 37 degrees C on a feeder layer of fibroblasts from embryos of Microtus montanus or CD-1 mice in HEPES-buffered Minimum Essential Medium with Earle's salts, supplemented with 15% heat-inactivated rabbit serum. When they were transferred to HEPES-buffered Cunningham's medium and incubated at 27 degrees C, they transformed into procyclic trypomastigotes, some of which developed into epimastigote and metacyclic forms in the presence of explants of Glossina morsitans or Phormia regina. Stages infective to mice were produced in cultures of procyclic forms grown with Anopheles gambiae cells in medium consisting of a mixture of 3 volumes of Cunningham's medium and 1 volume of Anopheles cell medium. In vitro-produced metacyclic trypanosomes were used to initiate cultures of bloodstream forms. PMID- 2896446 TI - Reproductive disorders in African trypanosomiasis: a review. AB - Reproductive disorders are frequently seen in human beings and in animals infected with tsetse-transmitted (African)trypanosomiasis. The disorders include irregular menstrual (or oestrus) cycle, infertility, abortion and impotence. Intrauterine infections occasionally occur, resulting in still birth or neonatal mortality. The changes are essentially reversible after treatment, although recovery may take several months. PMID- 2896445 TI - The relapse of Trypanosoma brucei brucei infections after chemotherapy in rabbits. AB - Infections of T. brucei in the rabbit were found to relapse after chemotherapy. The results indicated that 25 mg/kg diminazene aceturate given 3 days after infection resulted in a complete cure but if given 7 days after infection relapses frequently occurred. However, treatment was apparently successful if delayed until 14 or 21 days. Six of the rabbits originally treated with diminazene aceturate on day 7 were treated with suramin 21 days later; in 3 rabbits the infections relapsed. In all rabbits in which drug treatment was not curative, the clinical condition nevertheless improved. An attempt to locate a cryptic focus of infection in rabbits was unsuccessful. PMID- 2896447 TI - Formation of the circumsporozoite protein of Plasmodium falciparum in Anopheles stephensi. AB - The place and time of synthesis of the circumsporozoite protein of P. falciparum was analysed with a monoclonal antibody directed against the (NANP)3 repetitive epitope of the CS protein. By using an indirect fluorescent antibody test the epitope could be detected on the oocyst 7 days after infection and 3 days before the appearance of mature sporozoites. Using the Western blot technique, 3 polypeptides from midgut preparations were recognized by the (NANP)3-specific monoclonal antibody from the day 9 of infection onwards. The circumsporozoite precipitation reaction could be induced in sporozoites from either the midgut or the salivary glands 11 days after a blood meal. A similar reactivity of midgut sporozoites and salivary gland-sporozoites was observed with antisporozoite antisera. Not all sporozoites recovered from the midgut showed a precipitation reaction. PMID- 2896448 TI - Moulting and exsheathment of the infective larvae of Onchocerca lienalis (Filarioidea) in vitro. AB - Fourth-stage larvae (L4) of the cattle filarial parasite Onchocerca lienalis were produced from third stage forms (L3) and maintained in vitro using a variety of culture media and feeder cell layers. Up to 50% of the L3 larvae moulted to the fourth stage in the presence of two jird (Meriones unguiculatus) cell lines, a monkey kidney cell line and also with Vero cells. Moulting took place 2-5 days after of the initiation of the cultures: These L4 parasites could be maintained in a healthy condition for up to 88 days, although no significant increases in size of these larvae were observed during the culture period. The medium giving the most promising results, both in terms of moulting and survival, was 199 supplemented with heat inactivated foetal bovine serum (20%) and glucose (2 mg/ml). The feeder layer cells could be replaced by fresh jird red blood cells. Moulting of parasites occurred in medium alone but the viability was reduced under these conditions. PMID- 2896449 TI - Does dexamethasone suppress the Mazzotti reaction in patients with onchocerciasis? AB - The Mazzotti reaction is a frequent complication in patients with onchocerciasis being treated with diethylcarbamazine (DEC); and more severe manifestations of this reaction may be unacceptable in many patients. It has recently been demonstrated that prednisone modifies the severity of this reaction and reduces the microfilaricidal activity of DEC. A clinical trial was performed at the National Leprosy Training Center in Wau, Sudan, to evaluate the clinical and histologic effect of the use of corticosteroids in patients receiving DEC. Administration of a low dose of dexamethasone (3 mg/day), begun after onset of the Mazzotti reaction, modifies the progression of the Mazzotti reaction without interfering with the microfilaricidal efficacy of DEC. Pretreatment with low-dose dexamethasone--prior to beginning DEC therapy--prevents the development of the Mazzotti reaction and greatly reduces the microfilaricidal activity. Administration of diphenhydramine, after onset of the Mazzotti reaction, has no effect on the course and intensity of the Mazzotti reaction nor on microfilaricidal activity. We recommend that low-dose corticosteroids be administered in conjunction with DEC--after onset of the Mazzotti reaction--and that they be tapered rapidly. PMID- 2896450 TI - Parvaquone and buparvaquone: HPLC analysis and comparative pharmacokinetics in cattle. AB - A high performance liquid chromatographic (HPLC) method for the determination of the antitheilerial drugs parvaquone and buparvaquone in plasma was developed. Both compounds were extracted from plasma with ether. After evaporating the extracts to dryness the residue was dissolved in methanol and an aliquot was injected onto a column (10 cm X 5 mm, i.d.) of ODS-Hypersil (5 mu) with a mobile phase of 0.05 M-Na acetate buffer (pH 3.6)-methanol (15:85, v/v). Detection was at 252 nm. The mean recovery for both compounds was about 92%. This method was used to elucidate their pharmacokinetics in 6 calves after intramuscular administration. The maximum plasma concentration for parvaquone was 6.36 +/- 0.58 micrograms/ml after 0.84 +/- 0.08 h. The corresponding values for buparvaquone were 0.102 +/- 0.030 microgram/ml and 3.17 +/- 0.39 h, respectively. The decay in plasma concentrations for the two drugs was biexponential and the terminal elimination half lives were 11.12 +/- 1.63 h and 26.44 +/- 2.81 h for parvaquone and buparvaquone, respectively. PMID- 2896451 TI - A new apparatus suitable for the use of counter-immunoelectrophoresis in the field: application for the diagnosis of malaria and leishmaniasis. Short communication. PMID- 2896452 TI - Usefulness of isoproterenol in facilitating atrioventricular nodal reentry tachycardia during electrophysiologic testing. AB - In some patients with documented atrioventricular (AV) nodal supraventricular tachycardia (SVT), the arrhythmia is not inducible during a standard stimulation protocol. In these patients the level of sympathetic activity may be an important factor. This study evaluates the influence of isoproterenol on anterograde and retrograde pathway properties in patients with AV nodal SVT and the mechanism by which this SVT is facilitated. Group 1 consisted of 8 consecutive patients, ages 23 to 85 years (mean +/- standard error, 57 +/- 8) who had no inducible AV nodal SVT during electrophysiologic testing until isoproterenol (0.5 to 3.0 micrograms/min) was infused. These patients were compared with 6 patients in the same age range (45 to 78 years, mean +/- standard error, 64 +/- 5) who had inducible AV nodal SVT without isoproterenol and who comprised group 2. In comparing group 1 (before isoproterenol) with group 2, there was no significant difference in the refractory periods of the anterograde slow and fast pathways, although the anterograde block cycle length was longer in group 1 patients (421 +/- 18 vs 362 +/- 14 ms, p less than 0.05). The retrograde block cycle length was also longer in 7 of the 8 group 1 (before isoproterenol) patients in whom it could be measured versus those in group 2 (411 +/- 14 vs 318 +/- 27 ms, p less than 0.05). During isoproterenol, the anterograde and retrograde block cycle lengths in group 1 were not different from group 2. Therefore, AV nodal SVT may not be inducible in some patients during routine electrophysiologic testing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896453 TI - Atherogenic effects of beta blockers on cells cultured from normal and atherosclerotic aorta. PMID- 2896454 TI - Atrial automatic tachycardia in children. PMID- 2896455 TI - Effect of hospitalization on high-density lipoprotein cholesterol in patients undergoing elective coronary angiography. AB - The effects of time of sampling on plasma lipids and lipoprotein cholesterol concentrations were investigated in 88 patients undergoing elective coronary angiography. Patients with a myocardial infarction or major surgery within 6 weeks before catheterization were excluded. All subjects were sampled in the fasting state at the time of arteriotomy before systemic heparinization and at least 30 days after discharge from the hospital (mean 275 days) in the free living state. No statistically significant differences were noted in total cholesterol (220 +/- 51 vs 226 +/- 48 mg/dl), triglycerides (191 +/- 77 vs 191 +/ 113 mg/dl) and calculated low-density lipoprotein cholesterol levels (149 +/- 46 vs 150 +/- 43 mg/dl). High-density lipoprotein cholesterol values were significantly lower (p less than 0.0001) in subjects sampled before catheterization than in the free living state (32 +/- 10 vs 37 +/- 10 mg/dl, mean change 14%). Moreover, the frequency of high-density lipoprotein cholesterol less than 35 mg/dl was 77% before catheterization and 44% in the free living state. This effect was neither due to beta-adrenergic drugs nor to the length of time between samplings. In view of these findings, a screening lipid profile for patients with coronary artery disease should be performed in the free living state. PMID- 2896456 TI - Use of percutaneous transluminal coronary angioplasty and bypass surgery despite improved medical therapy for unstable angina pectoris. AB - To evaluate current strategies for the management of unstable angina, 104 consecutive patients admitted to the coronary care unit with unstable angina during a 6-month period were followed prospectively. Although 58 patients had symptomatic relief with the initiation of intensive medical therapy, 46 (44%) continued to have episodes of angina despite maximal tolerated triple-drug antianginal therapy as well as aspirin or heparin, or both. In-hospital mortality for the 104 patients was 4%. The incidence of myocardial infarction was 8%, and differed (p less than 0.01) for the medically responsive group (3%) vs the medically refractory group (13%). Based on clinical status and coronary anatomy, patients were referred for either bypass surgery (46%), coronary angioplasty (41%) or continued medical therapy (13%). Choice of therapy varied according to the extent of coronary disease, with coronary angioplasty attempted in 72% of patients with 1-vessel disease, 44% of patients with 2-vessel disease and 7% of patients with 3-vessel disease. Angioplasty was performed with an initial success rate of 88%, and compared favorably with bypass surgery in terms of in-hospital mortality (0 vs 11%), late mortality (2.8 vs 7.7%), freedom from angina (62 vs 69%) and subsequent employment (44 vs 27%) at 18 months follow-up. The favorable results of angioplasty in this prospective observational study suggest that additional randomized trials should be conducted in this important patient group. PMID- 2896457 TI - Protection of the ischemic myocardium during percutaneous transluminal coronary angioplasty. AB - Therapeutic balloon coronary angioplasty provides a useful model for studying the effects of epicardial coronary artery occlusion in conscious humans. In addition, it is a potent model in which the effectiveness of interventions designed to ameliorate ischemia can be evaluated. Whereas intravenous beta-adrenergic blocking drugs and nitrates appear to have a limited protective effect, the regional (i.e., intracoronary) use of beta-adrenergic blocking drugs and calcium antagonists seem more potent. Currently, coronary venous retroperfusion with arterial blood does not appear practical, and the intraaortic balloon is a useful adjunctive measure in relatively few patients undergoing percutaneous transluminal coronary angioplasty. In contrast, the direct anterograde delivery of oxygen-rich blood or fluorocarbons holds promise as a reliable means of providing local myocardial protection. If ischemia could be markedly reduced, percutaneous transluminal coronary angioplasty might be applied safely in more high-risk clinical settings. In addition, if prolonged balloon inflation could be performed, there might be an increase in primary success rate and possibly a reduction in restenosis rate. PMID- 2896458 TI - Sulfasalazine: I. An historical perspective. PMID- 2896459 TI - Sulfasalazine: II. Some notes on the discovery and development of salazopyrin. AB - In summing up: salazopyrin is an effective drug, particularly in ulcerative colitis. Serious adverse effects are remarkably rare. Salazopyrin provoked an improvement in 75-80% of cases of UC. It is excellently adapted for long-term treatment and, in this respect, is clearly superior to corticosteroids. It prevents relapses, particularly if the dosage is increased. The main indication for corticosteroids in UC is for acute attacks early in the course of the disease and to influence allergic symptoms during the disease. For acute swelling of the rectum, local treatment with corticosteroids or salazopyrin is often effective. Adverse effects occur in about 15% of cases treated with salazopyrin. They are due primarily to hypersensitivity to the drug. With very few exceptions, they disappear spontaneously or are controlled by corticosteroids or by some other treatment. The allergic pulmonary changes may give rise to a modest dyspnea, which is not fatal. The cyanotic and the yellow-coloring of the skin are harmless side effects. As to sulfa crystals in the kidneys and the urine, for the most part, they can be avoided by simple treatment. Agranulocytosis is a rare complication in the course of treatment with salazopyrin. During the 35 yr that the drug has been used, only 14 cases have been published in the literature. Of this number, three have died, but the treatment of the agranulocytosis is known in only one of them. Nonpublished cases probably exist, but this number does not seem to be great in my experience. In comparison with many other drugs (certain chemotherapeutics and antibiotics), the frequency of serious side effects caused by salazopyrin is remarkably low. PMID- 2896460 TI - Compatibility of esmolol hydrochloride with morphine sulfate and fentanyl citrate during simulated Y-site administration. AB - The compatibility and stability of esmolol hydrochloride in admixtures during simulated Y-site injection of morphine sulfate or fentanyl citrate was studied. One milliliter of either morphine sulfate (15 mg/mL) or fentanyl citrate (0.05 mg/mL) was injected into a running infusion of esmolol hydrochloride (10 mg/mL) in 5% dextrose and 0.9% sodium chloride injection, and the solution was visually observed for changes. To determine the stability of the drugs during Y-site injection, esmolol hydrochloride 4 mL (1000 mg) in 5% dextrose and 0.9% sodium chloride injection was combined with 100 mL of either morphine sulfate 15 mg/mL or fentanyl citrate 0.05 mg/mL to simulate concentrations of the drugs that might be expected during Y-site injection. The admixtures were stored at ambient room temperature under normal light, and drug concentrations were determined using high-performance liquid chromatography at time zero and at two, four, and eight hours. Admixtures were also tested for pH and observed for visual changes. No immediate changes were observed in any of the admixtures, and the concentrations of the drugs varied by less than 4% throughout the study period. No precipitate or color changes were noted during Y-site injection of either drug into the running esmolol infusion. Under all of the conditions studied, esmolol hydrochloride in 5% dextrose and 0.9% sodium chloride injection is compatible with morphine sulfate or fentanyl citrate. PMID- 2896461 TI - Manifestations of human T-lymphotropic virus type I infection. AB - HTLV-I, the first human oncovirus, is a type C retrovirus linked to the development of ATLL. The virus shows a striking ethnogeographic distribution that is only partially understood. Certain populations at high risk for AIDS appear to have a higher incidence of HTLV-I infection. The extended latent period renders present knowledge of the sequelae and natural history of HTLV-I seropositivity incomplete, although recent data suggest that HTLV-I infection may have important implications for blood transfusion, organ transfer, and public health policy. A variety of clinical syndromes have been associated with infection, ranging from an asymptomatic carrier state to acute ATLL with lymphadenopathy, hepatosplenomegaly, hypercalcemia, cutaneous lesions, and systemic immunosuppression. Conventional chemotherapy is marginally effective; innovative approaches to therapy are presently being evaluated. PMID- 2896462 TI - Prenatal diagnostic options in cystic fibrosis. AB - There are currently two diagnostic options in cystic fibrosis. These involve assays for certain microvillar enzyme activities in amniotic fluid and recombinant deoxyribonucleic acid studies of markers linked to the cystic fibrosis gene on chromosome 7. The former are reduced in cystic fibrosis homozygotes; the latter make it possible to determine the particular pattern of chromosome 7 markers predictive of a cystic fibrosis homozygote in a specific family. However, neither test is appropriate for, applicable to, or informative in all families. The problems and potential of each approach are discussed. PMID- 2896463 TI - Development of the muscarinic receptor in rabbit gastric smooth muscle. AB - We used binding of [N-methyl-3H]scopolamine ( [3H]-NMS) to tissue homogenates and isometric contraction of muscle strips to characterize perinatal changes in the muscarinic receptor on rabbit gastric smooth muscle. In homogenates from fetal (28 days of gestation), 1-, 3-, and 7-day, 4- and 11-wk-old rabbits, specific binding was saturable and temperature dependent, achieved equilibrium by 10 min at 30 degrees C, and was linearly related to tissue concentration. Specific binding was 80 +/- 2% of total binding at 0.2 nM [3H]NMS. The number of binding sites was 120,000 receptors/cell, maximal during the first week of life compared with the fetus or older animals. Affinity of [3H]NMS was highest in the first week of life (Kd = 345 +/- 24 pM, 1 day old). Age did not affect Hill coefficients or Ki values; secoverine and 4-diphenylacetoxy-N-methylpiperidine methiodide were 50-fold more potent than pirenzepine. In muscle strips, bethanechol stimulated dose-dependent atropine-inhibitable isometric contraction. The doses required for half-maximal contraction were similar in both age groups (5-6 microM), but maximal contraction was fivefold greater in weanlings compared with neonates. Increasing extracellular potassium concentration resulted in similar differences, suggesting that the differences were not receptor related. These results suggest that well-differentiated M2-muscarinic receptors are functional on rabbit gastric smooth muscle during the perinatal period. PMID- 2896465 TI - Autonomic nervous system pulmonary vasoregulation after hypoperfusion in conscious dogs. AB - We investigated the role of the autonomic nervous system (ANS) in the pulmonary vascular response to increasing cardiac index after a period of hypoperfusion (defined as reperfusion) in conscious dogs. Base-line and reperfusion pulmonary vascular pressure-cardiac index (P/Q) plots were generated by stepwise constriction and release, respectively, of an inferior vena caval occluder to vary Q. Surprisingly, after 10-15 min of hypoperfusion (Q decreased from 139 +/- 9 to 46 +/- 3 ml.min-1.kg-1), the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) was unchanged over a broad range of Q during reperfusion compared with base line when the ANS was intact. In contrast, pulmonary vasoconstriction was observed during reperfusion after combined sympathetic beta-adrenergic and cholinergic receptor block, after beta block alone, but not after cholinergic block alone. The pulmonary vasoconstriction during reperfusion was entirely abolished by combined sympathetic alpha- and beta-block. Although sympathetic alpha-block alone caused pulmonary vasodilation compared with the intact, base-line P/Q relationship, no further vasodilation was observed during reperfusion. Thus the ANS actively regulates the pulmonary circulation during reperfusion in conscious dogs. With the ANS intact, sympathetic beta-adrenergic vasodilation offsets alpha-adrenergic vasoconstriction and prevents pulmonary vasoconstriction during reperfusion. PMID- 2896464 TI - Endothelium inhibits norepinephrine release from adrenergic nerves of rabbit carotid artery. AB - The overflow of endogenous norepinephrine caused by transmural electrical stimulation or depolarization with potassium was smaller in superfused segments of the rabbit carotid artery with intact endothelium than in segments denuded of endothelium. In segments preincubated with [3H]norepinephrine, the lesser overflow was found to be partially due to metabolism by the endothelium of the neurotransmitter. Even after treatment to block the disposition of norepinephrine, the endothelium acted as a partial physical barrier to the overflow of norepinephrine into the lumen of arteries superfused and perfused selectively. However, a lesser overflow of norepinephrine to the adventitia of the artery accounted for the majority of the difference in overflow between segments with and without endothelium. The inhibition by the endothelium of the overflow of norepinephrine from adrenergic nerves was unaffected by blocking prejunctional alpha 2-adrenoceptors, prostaglandin synthesis, free radicals, or guanylate cyclase. Vasodilators released from the endothelium of a donor artery inhibited contractions caused by adrenergic nerve stimulation of a bioassay artery but failed to inhibit norepinephrine release. These observations indicate that the endothelium 1) metabolizes norepinephrine, 2) acts as a physical barrier to its overflow into the blood vessel lumen, and 3) inhibits the release of the adrenergic transmitter from adrenergic nerves. PMID- 2896466 TI - Postsynaptic adrenoceptor-mediated vasoconstriction in coronary and femoral vascular beds. AB - This study examined the response to intra-arterial norepinephrine and sympathetic nerve stimulation on perfusion pressure of cannulated dog femoral and left circumflex coronary arteries perfused at constant flow rates. Sympathetic nerve stimulation was delivered through the decentralized inferior cardiac nerve and the lumbar sympathetic chain; beta-adrenergic blockade was maintained with propranolol. In the coronary artery, the vasoconstrictor response to norepinephrine was blunted by alpha 1-adrenergic blockade with prazosin but was abolished by alpha 2-adrenergic blockade with rauwolscine, indicating postsynaptic alpha 2-adrenoceptor-mediated vasoconstriction. In the femoral artery, prazosin decreased norepinephrine-induced vasoconstriction by 20-40%; the subsequent addition of rauwolscine completely abolished vasoconstriction, indicating that both alpha 1- and alpha 2-adrenoceptors contributed to vasoconstriction. Sympathetic nerve stimulation produced frequency-dependent increases of perfusion pressure in both coronary and femoral vascular beds. Prazosin caused approximately 50% reduction in the vasoconstrictor response of the coronary vascular bed and approximately 30% reduction in the femoral bed. The addition of rauwolscine completely blocked the response to sympathetic nerve stimulation in coronary and femoral vascular beds. These studies demonstrate that postsynaptic alpha 2-adrenoceptor-mediated mechanisms participate in vasoconstriction in response to both exogenous norepinephrine and sympathetic nerve stimulation in the canine coronary and femoral vascular beds. PMID- 2896467 TI - Pharmacological influence of antiallergic medication on in vivo allergen testing. PMID- 2896468 TI - Anaphylactoid reaction to vecuronium followed by systemic reaction to skin testing. AB - An unusual case is presented of a systemic anaphylactoid reaction to tubocurarine and subsequently to vecuronium. Intradermal testing with vecuronium following the latter response was negative at recommended test dose levels but at a higher concentration it initiated a hazardous systemic response. The laboratory investigations and possible mechanisms involved in this unusual case are discussed in detail since they may relate to other patients who experience anaphylactoid responses to anaesthetic drugs and who then undergo intradermal testing. PMID- 2896469 TI - On the hazards of priming. PMID- 2896470 TI - Prolonged neuromuscular blockade with vecuronium in renal failure. PMID- 2896471 TI - Intra-ocular pressure changes during induction of anaesthesia and tracheal intubation. A comparison of thiopentone and propofol followed by vecuronium. AB - Intra-ocular pressure was measured during induction of anaesthesia with propofol (n = 40) or thiopentone (n = 40) followed by vecuronium to facilitate tracheal intubation which was carried out 3 minutes after the administration of relaxant. The average induction doses were 2.15 and 4.83 mg/kg for propofol and thiopentone, respectively. Half the patients in each group received a supplementary dose of the same induction agent (propofol 1.0 mg/kg or thiopentone 2.0 mg/kg) (corrected) prior to intubation. Both propofol and thiopentone produced a significant reduction in intra-ocular pressure which decreased further after administration of vecuronium as well as the second smaller dose of the induction agents. Intra-ocular pressure prior to intubation was lower in the two propofol groups in comparison to the corresponding thiopentone groups. Intubation was associated with an increase in intra-ocular pressure but it still remained significantly below the baseline values except in the group given one dose of thiopentone. Supplementary doses of induction agents before intubation attenuated the increase in intra-ocular pressure. Propofol was significantly more effective in this respect and this group showed the lowest intra-ocular pressure throughout the study period. However, administration of propofol resulted in a 30% incidence of pain on injection and a decrease in systolic arterial pressure of more than 30% in about half the patients. PMID- 2896472 TI - Anaphylactoid reaction to vecuronium. PMID- 2896473 TI - A nonisotopic method for determination of the in vivo activities of tyrosine hydroxylase in the rat adrenal gland. AB - A rapid and reliable method for determination of in vivo activities of tyrosine hydroxylase in the rat adrenal gland is presented. This method involves determining the rate of accumulation of 3,4-dihydroxyphenylalanine (Dopa) in the adrenal gland after decarboxylase inhibition by NSD 1015, using HPLC with electrochemical detection after purification of the acid-deproteinized tissue extract with Bio-Rex 70 columns followed by alumina batch method. Purification of the sample with alumina adsorption alone, a method usually used for purification of catecholamines and Dopa, was ineffective: epinephrine and norepinephrine, which are present in high concentrations, interfered with an accurate determination of Dopa, and dopamine, which is retained strongly on the reverse phase column, interfered with a rapid analysis. Purification with Sephadex G-10 columns followed by alumina adsorption was also ineffective. After purification with columns of weak cation-exchange resins such as Bio-Rex 70 or Amberlite CG-50 followed by alumina adsorption, most of the epinephrine and norepinephrine was removed and dopamine was eliminated. Thus a rapid and accurate determination of Dopa could be made. Of the two cation exchangers, Bio-Rex 70 was more effective. Accumulation of Dopa in the adrenal gland was linear up to 30 min after administration of NSD 1015 and a plateau was reached with doses over 10 mg/kg. Using this method, we investigated the effects of immobilization stress, reserpine, and hypoxia on in vivo activities of tyrosine hydroxylase in the adrenal gland. PMID- 2896474 TI - The distribution of terminal sympathetic nerve fibers in bundle branches and false tendons of the bovine heart. An immunohistochemical and catecholamine histofluorescence study. AB - The sympathetic innervation in false tendons as a whole and the distribution of the terminal sympathetic nerve fibers in the conduction tissue in the bundle branches is unclear. Therefore, in the present study, false tendons and bundle branch regions of the bovine heart were examined using tyrosine hydroxylase (TH) immunohistochemistry and the glyoxylic acid induced catecholamine (CA) fluorescence method for demonstration of sympathetic nerve fibers. Acetylcholinesterase (AChE) histochemistry was also applied. Some of the nerve fascicles in the false tendons were found to contain large numbers of sympathetic nerve fibers and such nerve fibers formed plexuses in the walls of arteries and arterioles in these structures. In both false tendons and bundle branches sympathetic nerve fibers 1) were non-homogeneously distributed in the conduction tissue, most regularly occurring in the channels of extracellular space that are present within the bundles of Purkinje fibres, and 2) showed the same pattern of distribution in relation to Purkinje fibre bundle surfaces as the AChE-positive nerve branches. The observations show that there is a substantial sympathetic innervation in false tendons. The final distribution of the nerve fibers in these structures and in the bundle branches are discussed in relation to what is known of tissue morphology and the occurrence of sympathetic nerve influences in these regions. In the present study, previous CA-fluorescence observations of a "marked" sympathetic innervation in bundle branch regions, in terms of the presence of sympathetic nerve fibers in nerve fascicles and vessel walls, were also corroborated by the application of TH-immunohistochemistry. PMID- 2896476 TI - An unusual case of occlusive thromboaortopathy (Takayasu's disease)--a case report. AB - A case of Takayasu's disease presenting in a young man as a solid abdominal mass is described. The literature is reviewed and classifications of the disease are discussed. Occlusive thromboaortopathy, also known as "pulseless disease" or Takayasu's disease, was first described in 1908 by Takayasu, who observed cataracts and peculiar arteriovenous anastamoses around the optic papillae in a young woman. It is a vasculitic disorder of uncertain etiology occurring mainly in young women and may involve part or most of the aorta, as well as the pulmonary artery. Early features include fever, malaise, weight loss, and a high ESR, and, later on, absent pulses, aneurysms, hypertension, and heart failure may occur. The authors describe an unusual case of Takayasu's disease in a young black South African man. PMID- 2896475 TI - [Effect of adrenoblocking agents and melipramine on the analgesic effect of non narcotic analgesics]. PMID- 2896477 TI - [Management of peroperative hypertensive crises]. PMID- 2896478 TI - [Almitrine temporarily suppresses respiratory depression caused by buprenorphine]. PMID- 2896479 TI - [Use of new inotropic agents in the treatment of acute cardiac failure]. AB - The drugs, new and old, useful in the treatment of acute cardiac failure, are reviewed in the light of its pathophysiological mechanisms and of the biochemical aspects of myocardial contraction. Two major classes of drugs are considered, those that stimulate cell membrane adenylcyclase, i.e. beta-agonists (dopamine, dobutamine and dopexamine) and alpha-agonists (glucagon, forskolin, calcium agonists) and those that inhibit the cellular phosphodiesterases, i.e. bipyridine derivatives (amrinone and milrinone) and imidazolone derivatives (fenoximone and piroximone). Virtually, all the inotropic agents act by increasing the entry of calcium into the cell by increasing the intracellular AMPc concentration. Dopamine has a dose-related triphasic activity. At low doses, stimulation of renal dopaminergic receptors increases renal blood flow, glomerular filtration rate and sodium clearance. At moderate doses, dopamine stimulates, for the most part, cardiac beta-adrenergic receptors. Higher doses stimulate alpha-1 adrenergic receptors, with an increase in systemic arterial and venous pressures. Dobutamine exerts a potent positive inotropic action, with little effect on vascular tone and less tachycardia than with other catecholamines, resulting in only a slight increase in myocardial oxygen consumption. The dopamine analogue, dopexamine, increases renal blood flow, myocardial contractility and produces peripheral vasodilation. The haemodynamic effects of phosphodiesterase inhibitors are similar to those of dobutamine, except that these drugs are vasodilators, their positive inotropic properties are weak and their haemodynamic effects persist for at least 8 h after a single dose in heart failure patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896480 TI - Dopamine, acetylcholine, and glutamate interactions in aging. Behavioral and neurochemical correlates. AB - Aging, hypoxia, and thiamin deficiency diminish motor performance. Similar alterations of ACh, DA, and glutamate metabolism accompany hypoxia, thiamin deficiency, and aging. Both aging and hypoxia reduce ACh release and stimulate DA and glutamate release. Presynaptic enhancement of DA and glutamate release may be important in the production of cell damage that may contribute, in part, to age related deficits in motor as well as cognitive function. The decline in ACh release may be important in the production of the cognitive deficits. An understanding of the interactions of neurotransmitters in hypoxia and thiamin deficiency aids our understanding of normal aging and increases the possibility of developing better treatments for the multiple neurotransmitter deficiencies that accompany many metabolic, age-related, and chronic degenerative disorders. PMID- 2896481 TI - Ganglioside treatment in the recovery of the DA nigrostriatal system in different experimental conditions. PMID- 2896483 TI - Luteinizing hormone-releasing hormone in rat brain: gene expression, role as neuromodulator, and functional effects. PMID- 2896482 TI - Luteinizing hormone-releasing hormone as a neurotransmitter in bullfrog sympathetic ganglia. PMID- 2896484 TI - Cefotaxime-sensitive Aeromonas hydrophila infection in a revascularized foot. AB - Three days following revascularization of a foot injured in a boating accident, Aeromonas hydrophila cellulitis developed in the victim's foot and leg. The infection resolved with debridement and 10 days of cefotaxime therapy. A. hydrophila infection has not previously been reported in a revascularized extremity. Clinical response of an A. hydrophila cellulitis to cefotaxime is likewise undescribed. Our findings of a cefotaxime-sensitive Aeromonas infection and its successful treatment suggests that the organism should undergo further evaluation of cefotaxime sensitivity and that cefotaxime and other third generation cephalosporins may have a role as broad-spectrum antibiotic agents in fresh-water trauma. PMID- 2896485 TI - [Reconstruction in 3D of the foot: preliminary technical study]. PMID- 2896486 TI - Renal gamma-glutamyl transpeptidases: structural and immunological studies. AB - Mammalian kidney gamma-glutamyl transpeptidases are compared with respect to subunit size, amino-terminal sequences of the two subunits, immunological, and some catalytic properties. The species-related variation in the apparent molecular weight of the subunits has been shown to be primarily due to the extent and nature of protein glycosylation. Using antibodies raised against the native enzymes and isolated sodium dodecyl sulfate-treated subunits, it is shown that the transpeptidases share some antigenic determinants. Some of these determinants in the highly glycosylated transpeptidase subunits can be detected by the antibodies only upon deglycosylation of the subunits. The amino-terminal sequences of the subunits exhibit considerable homology, in agreement with the immunological data. Thus, there are two segments of identity (3 and 5 residues in length, respectively) in the first 17 amino-terminal residues of the heavy subunits of rat, bovine, dog, and human kidney transpeptidases (papain solubilized). Of particular interest is the finding of 91 to 96% identity in the first 23 amino-terminal residues of the small subunit of these transpeptidases. The small subunit contains the gamma-glutamyl binding site of the enzyme. There are three segments of identity (7, 6, and 8 residues in length, respectively) in the first 23 residues, each separated by either a Ser or an Ala residue. The first 7 amino-terminal residues of the small subunit in all four species are identical, indicating a high degree of specificity in the proteolytic processing of the common, single-chain precursor of the two subunits. Differences noted between transpeptidases in their relative acceptor specificity and in their susceptibility to inactivation by the glutamine antagonist, AT-125 (acivicin), must reflect subtle structural differences in their active center domains. PMID- 2896487 TI - Involvement of postsynaptic adrenergic mechanism(s) in the ATP-contractions of the rat anococcygeus muscle and the effect of extracellular Ca2+. AB - Clonidine, ICI-106270 (6-aryl 2,367 tetrahydro 5-H-pyrrolo(1,2-a)-imidazole derivative), B-HT-920 (6-Allyl-2-amino-5,6,7,8-tetrahydro-4H-thiozolo = [4,5 d]azepine-dihydrochloride, and guanfacine, agonists at alpha 2-adrenoceptors, produced concentration-dependent contractions of the rat anococcygeus muscle. The order of potency of these agonists in producing the response was clonidine greater than ICI-106270 greater than guanfacine greater than B-HT 920. Yohimbine (10(-6) M) competitively antagonized the contractile response due to these agents acting at alpha 2-adrenoceptors. ATP (10(-6) M-10(-4) M) also produced concentration-dependent contractions of the rat anococcygeus muscle. Prazosin (10(-8) M) an alpha 1-blocker, significantly antagonized ATP-induced contractions in a competitive manner. ATP (10(-7) M) in a concentration that had no effect on basal tension of the preparation, tends to potentiate phenylephrine responses, though not significantly. The sensitivity of the anococcygeus muscle to ATP was enhanced after 24 hr (maximum catecholamine depletion period) of reserpine (5 mg/kg, i.p.) treatment. Yohimbine (10(-6) M), a selective alpha 2-blocker, significantly antagonized ATP-induced contractions and shifted the ATP concentration-response curve towards right. The antagonism was found to be competitive. The ATP-contractions were also sensitive to inhibition by reduced calcium contents (quarter or calcium free) in the Krebs bicarbonate solution. However, it was observed that ATP was capable of producing contractions of anococcygeus muscle even in Ca-free Krebs bicarbonate solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896489 TI - Pharmacological evaluation of in vivo tests for alpha 2-adrenoceptor blockade in the central nervous system and the effects of the enantiomers of mianserin and its aza-analog ORG 3770. AB - A series of compounds with actions on the central nervous system was tested for antagonism of clonidine-induced sleep in chicks and clonidine-induced mydriasis in rats for the purpose of evaluating these methods as tests for demonstrating an in vivo alpha 2-adrenoceptor blocking effect of a novel compound. Clonidine induced mydriasis was found to be the most selective method. The order of potency for compounds fully antagonizing clonidine-induced mydriasis was MSD 26 greater than physostigmine = idazoxan greater than aptazapine greater than piperoxan greater than yohimbine greater than mianserin greater than tolazoline. Partial antagonism was found for quipazine and sulpiride. Misleading results can arise from the involvement of cholinergic mechanisms in the control of the pupil diameter. The order of potency for compounds antagonizing clonidine-induced sleep in chicks was apomorphine greater than yohimbine greater than idazoxan greater than aptazapine = MSD 26 greater than quipazine greater than methysergide greater than piperoxan = mianserin = bepridil = metergoline = cyproheptadine = desipramine greater than tolazoline greater than dexchlorpheniramine, although antagonism was not complete for all of these compounds. Misleading results can arise from effects on arousal of the chicks but cholinergic mechanisms do not play a disturbing role so that the method with chicks can be a useful supplement to the mydriasis method. The enantiomers of mianserin and of a compound related to mianserin, Org 3770, were tested in the 2 methods and the alpha 2-blocking effect of these compounds was found to be residing in the S(+)-enantiomers. PMID- 2896488 TI - Comparative study of direct coronary vascular responses to diltiazem, adrenergic beta-blockers and other vasodilators in isolated, perfused dog and monkey coronary arteries. AB - The cannula-inserting method was used to examine the vascular responses of the isolated, perfused dog and monkey coronary arteries to a calcium antagonist (diltiazem), adrenergic beta-blockers (propranolol and pindolol), an antianginal drug (nicorandil) and vasodilators (hydralazine and papaverine). Propranolol and pindolol constricted the dog and monkey coronary arteries dose-dependently. Without any precontraction, hydralazine produced a biphasic response--a vasodilatation followed by a vasoconstriction--in the dog coronary artery, although it produced only a vasodilatation in the monkey coronary artery. Nicorandil and diltiazem dilated the uncontracted dog and monkey coronary arteries dose-dependently. The rank order of drug potency for inducing vasodilatation was diltiazem greater than nicorandil greater than hydralazine in both coronary arteries. These results indicate that the cannula-inserting method is useful to investigate the responses of the large epicardial dog and monkey coronary arteries to vasodilating drugs. PMID- 2896491 TI - Blood pressure control and levels of gamma-glutamyl transferase. PMID- 2896490 TI - Effect of beta-adrenoceptor stimulation or blockade on regional myocardial function and regional O2 consumption during myocardial ischemia. AB - The purpose of this study was to determine the effect of beta-adrenoceptor activation and blockade on the relationship between regional myocardial function and regional O2 consumption in ischemic and nonischemic myocardium. Myocardial regional segmental function was assessed in 28 open chest, anesthetized dogs using subepicardial dimension gauges. Ten min after LAD (left anterior descending coronary artery) occlusion, dogs were given i.v. saline, 2 mg/kg propranolol, 0.2 mg/kg pindolol, or 1 microgram/kg/min isoproterenol. Coronary blood flow was determined using radioactive microspheres before LAD occlusion, 10 min after occlusion, and 2 hr after LAD occlusion. Regional O2 consumption was determined using microspectrophotometry. LAD occlusion did not alter any index of myocardial function measured in the nonischemic region, but in the ischemic region, end systolic length (ESL) was increased 20% while shortening was converted to systolic bulging. No agent resulted in an improved ischemic regional function or an altered O2 consumption during LAD occlusion. In the nonischemic region the per cent shortening was increased 60% with isoproterenol compared to control. Propranolol and pindolol both increased the non-schemic regional ratio of per cent shortening vs O2 consumption significantly, suggesting an improved efficiency while isoproterenol lowered this ratio. When per cent shortening was plotted vs regional O2 consumption for all treatments, a significant linear relationship was observed in the nonischemic region. Thus, no drug treatment used in this study significantly improved central ischemic regional function, or O2 consumption, but both beta-adrenoceptor blockers seemed to result in an improved relationship between segmental shortening and O2 consumption in the nonischemic region. PMID- 2896494 TI - Common dentoalveolar emergencies. PMID- 2896492 TI - [Comparative studies of the practical use of different sperm samples]. AB - Comparative Investigation of Six Different Searching Techniques for Seminal Stains The comparison of six searching methods showed, that the phosphatase test has the highest, the choline test a sufficient and the other tests a poor sensitivity. Stains of seven body secretions and excretions, 13 fruit and 17 vegetables have been investigated by damp filter paper method. The spermine-, gamma-glutamyltranspeptidase-, and the zinc test had an insufficient specificity. The phosphatase test had false positive results with kiwi fruit, cauliflower, pea, and potato; the choline test with cauliflower, pea, broccoli, leek, and tomato; the leucineaminopeptidase test with feces and strawberry. PMID- 2896493 TI - Acute beta-blocker withdrawal and exchange by verapamil before percutaneous transluminal angioplasty. PMID- 2896495 TI - New technologies for studying human genetic variation. PMID- 2896496 TI - Genes encoding drug-metabolizing enzymes: possible role in human disease. PMID- 2896497 TI - Molecular biology and infectious diseases: the Institut Pasteur marks its first century. PMID- 2896498 TI - Study on the role of endogenous polyamines in glucagon, isoproterenol or serum mediated induction of tyrosine aminotransferase in cultured heart cells. AB - In confluent and serum-starved embryonic heart cell cultures, the addition of serum (10%), glucagon (GLU, 0.1 microM) or isoproterenol (ISO, 10 microM), causes the onset of ornithine decarboxylase (ODC) activity, with a maximum after 5-6 hr. This is paralleled by polyamine accumulation and by the induction of TAT, which, in the case of GLU and ISO, exhibits maximal activity at 4-3 hr respectively, followed by a net decline. Cyclic AMP (cAMP) also accumulates after exposure to GLU or ISO. However, under different conditions of ODC inhibition, serum fails to induce TAT, thus supporting a relevant role of cellular polyamines in serum action. Conversely, cAMP and TAT responses to GLU or ISO are markedly improved under prevention of polyamine accumulation, which also leads to a longer lasting TAT inducibility. The suggestion is made that polyamines are not required in the cAMP-dependent mechanism of TAT induction, but rather in the restoration of the basal activity of the enzyme. PMID- 2896499 TI - Transamidating activities of factor XIIIa and of transglutaminases, measured by an ELISA procedure. AB - The dansyl hapten in dansylcadaverine offers unique possibilities for measuring the incorporation of the monoamine into proteins (e.g. N,N'-dimethylcasein) by transamidating enzymes such as factor XIIIa and the transglutaminases. The protein-bound dansylcadaverine was assayed by an ELISA procedure based on a monoclonal antibody to the dansyl moiety. PMID- 2896500 TI - Reduced cyclosporin accumulation in multidrug-resistant cells. AB - Cyclosporin accumulation was reduced by 50% or more in multidrug- resistant CHRC5 CHO cells with high levels of P-glycoprotein expression compared to drug sensitive AuxB1 CHO cells. This difference could be overcome by verapamil which is known to interact with P-glycoprotein and reverse multidrug resistance. The difference in cyclosporin accumulation between sensitive and resistant cells decreased with increasing cyclosporin concentrations suggesting that cyclosporine itself regulated its own accumulation through interaction with P-glycoprotein. Indeed, cyclosporin also reversed differences in vinblastine accumulation between resistant and sensitive cell lines. Since P-glycoprotein is highly expressed in the kidney which is also a target for cyclosporin toxicity, the effects of verapamil on cyclosporin accumulation were studied in two renal cell lines, rat mesangial cells and LLCPK1, cells. Verapamil increased cyclosporin accumulation by approximately 70%. These results suggest that cellular cyclosporine accumulation is regulated at least in part by its interaction with P glycoprotein. PMID- 2896501 TI - Subtle alteration of the active site of ribulose bisphosphate carboxylase/oxygenase by concerted site-directed mutagenesis and chemical modification. AB - Both activities of ribulose bisphosphate carboxylase/oxygenase are dependent on carbamylation by CO2 of a specific lysyl epsilon-amino group (Lys-191 of the enzyme from Rhodospirillum rubrum). To examine the stringency of the requirement for this lysyl side chain, Lys-191 was converted to an aminoethylcysteinyl residue (net replacement of a gamma-methylene group by a sulfur atom) by a combination of site-directed mutagenesis and subsequent chemical modification. The purified Cys-191 mutant was totally devoid of both carboxylase and oxygenase activities. However, this mutant protein exhibited tight-binding of the transition-state analogue, 2-carboxyarabinitol bisphosphate, a property heretofore ascribed solely to the carbamylated form of the carboxylase. Treatment of the mutant protein with ethylene imine restored catalytic activity to 4-7% of the wild-type level. The carboxylase:oxygenase activity ratio of the aminoethylated protein was unperturbed relative to that of wild-type enzyme. PMID- 2896502 TI - Acidic pH- and metal ion (Zn++ or Mn++)-dependent proteolysis of 140 kDa atrial natriuretic factor receptor in bovine adrenal cortex plasma membranes: evidence for membrane-bound acidic metalloendopeptidase. AB - Incubation of the adrenal membranes at pH 3.5-5.6 resulted in apparent proteolysis of 140 kDa protein to yield a 70 kDa polypeptide containing an ANF binding site, which could be photoaffinity labeled by [125I]4-azidobenzoyl monoiodo ANF-(4-28). This 70 kDa fragment was found to be disulfide-linked to the remaining segment(s) of the molecule, giving a total apparent Mr of 140,000 when not reduced. The acidic pH-dependent proteolysis was rapid even at 0 degree C, suggesting close association of an endopeptidase with ANF receptor. The proteolysis was inhibited by EDTA, but not by phenylmethanesulfonyl fluoride, N ethylmaleimide or pepstatin, indicating that the enzyme is a metalloendopeptidase. The inhibition was reversed by ZnCl2 or MnCl2, but not CaCl2 or MgCl2. The adrenal membranes contained guanylate cyclase activity of 1.1 nmol/min/mg protein using Mn-GTP as a substrate, which could be stimulated by 0.1 microM ANF to 2.7 nmol/min/mg. The membranes showed high affinity to ANF-(1-28) and ANF-(4-28), but little affinity to the truncated peptides ANF-(5-25) and ANF (7-23). After treatment at pH 3.5 and 0 degrees C for 15 min, the membranes retained ANF-binding activity but with broader specificity, exhibiting high affinity to all four peptides above. It was suggested that an acidic metalloendopeptidase in the adrenal membranes may be involved in ANF receptor cleavage. PMID- 2896503 TI - Anion-dependent modulations of DNA topoisomerase II-mediated reactions in potassium-containing solutions. AB - DNA binding proteins operate in an intracellular environment of low chloride concentration, yet in vitro assays of the activities of these proteins are often performed in isotonic chloride-containing solutions. Previously, the activity of bacterial DNA-binding proteins was found to be enhanced in potassium-containing solutions in which the anion glutamate (Glu) was substituted for chloride. We have extended this observation to include eukaryotic topoisomerase I and II activities. The concentration ranges over which DNA strand passing activities of these enzymes were observed was broader in KGlu than in KCl. This was also true for the topoisomerase II-mediated DNA strand passage and antineoplastic drug dependent DNA cleavage produced by nuclear extracts from HL-60 human leukemia cells. The rate of topoisomerase II-mediated DNA strand passage was also dependent on anion moiety and concentration in potassium-containing buffers. Drug dependent topoisomerase II-mediated DNA cleavage in intact HL-60 cell nuclei was also anion-dependent, suggesting that anion type and concentration may influence topoisomerase II-mediated events in mammalian cells as had been described for other DNA binding proteins in prokaryotic systems. This should be considered in developing biochemical assays of topoisomerase activities to reproduce intracellular conditions. PMID- 2896504 TI - Binding of dicyclohexylcarbodiimide to a native F1-ATPase-inhibitor protein complex isolated from bovine heart mitochondria. AB - The effect and the binding of dicyclohexylcarbodiimide (DCCD) to a soluble native F1-ATPase-inhibitor protein complex (F1-IP) isolated from heart mitochondria was studied. About one mol DCCD bound per mol F1-IP complex; this inhibited its ATPase activity by more than 95%, ever under conditions that led to maximal hydrolysis. Bound DCCD localized to beta-subunits of the F1-IP complex. Cross linking of the DCCD labeled complex with N-(ethoxy-carbonyl)-2 ethoxydihydroquinoline yielded a protein with a Mr 65,000-67,000 that contained IP as evidenced by its reaction with IP antibodies. No alpha-subunits were detected in this cross-linked product. The Mr 65,000-67,000 protein corresponds to beta-subunits cross-linked with IP (Klein et al, Biochemistry 1980; 19, 2919 2925). However, no DCCD was found in the cross-linked beta-subunit-IP product of labeled native F1-IP. Thus the beta-subunit in contact with IP is distinct from the other two beta-subunits of the enzyme. PMID- 2896505 TI - Pharmacological effects of the antianxiety compound suriclone and its principal metabolites. AB - The pharmacodynamic effects of 4-methyl-1-piperazinecarboxylic acid ester with (+/-)-6-(7-chloro-1,8-naphthyridin-2-yl)-2,3,6,7-tetrahydro-7-h ydr oxy-5H-p- dithiino[2,3-c]pyrrol-5-one (suriclone, RP-31264) and its principal metabolites M1 and M2 on respiration, cardiovascular system, autonomic nervous system, smooth muscle and other physiological parameters were investigated in various animal species. Suriclone, 1 mg/kg i.v., increased the amplitude of respiratory movement, decreased the respiratory rate and blood pressure and increased the heart rate in conscious rabbits. The respiratory and depressor effects were more evident in pentobarbital anesthetized rabbits. In anesthetized dogs, suriclone, 0.05 or 0.5 mg/kg i.v., produced essentially the same effects as seen in the anesthetized rabbits. The ECG pattern was not significantly changed in any animal. Such effects on respiration and on the cardiovascular system of metabolites M1 and M2 in the rabbits were weak. In the isolated guinea-pig atria, suriclone, 10(-6) g/ml, had no effect but increased contractility and decreased heart rate at a high concentration of 10(-5) g/ml. Both M1 and M2 had weak effects. Suriclone had no action on flow rate of the perfusate through the blood vessels of the isolated rabbit ear. In anesthetized dogs, suriclone 0.5 mg/kg i.v., did not affect the responses to vagal stimulation or to pre- and postganglionic stimulation of cardiac ganglion. Suriclone instilled onto the eye or i.v. had no appreciable effect on pupillary diameter or the miotic response in rabbits, but an abnormal oculogyration was evoked when the drug was given i.v. at 1 mg/kg. M1 or M2 had no such effect. Suriclone did not exert analgesic effects in mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896506 TI - [Effect of different beta-receptor blockers on the respiratory function of patients with chronic obstructive pulmonary disease and arterial hypertension]. AB - 20 patients with confirmed diagnoses of arterial hypertension and chronic obstructive pulmonary disease were studied. Groups of 10 patients each were treated with propranolol 2 X 40 mg p.o. or betaxolol (Kerlone) 20 mg p.o., respectively. Pulmonary function, blood pressure and heart rate were assessed before and at 2, 4 and 6 h after administration of the first tablet on day 1 of the study. The same parameters were recorded 2 h after ingestion of the morning dose on each of the following days. Both drugs caused comparable significant decreases in blood pressure and heart rate on the 1st day of treatment. Propranolol was associated with a documented increase in the degree of bronchial obstruction. PMID- 2896507 TI - Effect of the alpha 1-blocker bunazosin on reperfusion-induced mitochondrial dysfunction in canine hearts. AB - The effect of the alpha 1-blocker 4-amino-2-(4-butyryl-hexahydro-1H-1,4-diazepin 1-yl) -6,7-dimethoxy-quinazoline (bunazosin, E-643, Detantol) on reperfusion injury was investigated. 43 anesthetized dogs were divided into two groups: the control group (n = 30) and the bunazosin group (n = 13). 15 min after premedication with physiological saline for the control group, or the alpha 1 blocker bunazosin 0.5 mg/kg for the bunazosin group, the left anterior descending coronary artery was occluded for 15 min and then reperfused for 5 min. Heart mitochondria were prepared from both the normal and reperfused areas. Mitochondria function and their Ca2+ content were measured by polarography and atomic absorption, respectively. Mitochondrial phospholipase activity was measured by high performance liquid chromatography. Nine dogs (30%) of the control group developed reperfusion arrhythmias. None of those pretreated with bunazosin developed arrhythmias. Although mitochondrial dysfunction was observed in the reperfused area in each group, more severe dysfunction was observed in dogs with arrhythmias in the control group. Mitochondrial Ca2+ content in the reperfused area in dogs with arrhythmias increased significantly compared with that in the normal area. Phospholipase activity in the reperfused area in dogs with arrhythmias also increased significantly, but no significant elevation of phospholipase activity was observed in dogs without arrhythmias in both the control and bunazosin groups. These results indicate that reperfusion injury might be closely related to activation of phospholipase linked with alpha 1 adrenergic response. PMID- 2896508 TI - A multicentric study of loratadine, terfenadine and placebo in patients with seasonal allergic rhinitis. AB - This multicentric study compared 14-day treatment with loratadine (Clarityne) 10 mg once daily, terfenadine 60 mg twice daily and placebo in outpatients with seasonal allergic rhinitis. Of 275 patients enrolled, 256 (87 in the loratadine group, 89 in the terfenadine group and 80 in the placebo group) were evaluable for efficacy and 266 (90, 91 and 85 in respective groups) were evaluable for safety. Investigators graded the severity of 4 nasal and 4 nonnasal signs/symptoms and investigators and patients rated overall disease condition and therapeutic response on treatment days 3, 7 and 14; patients recorded when signs/symptoms of rhinitis were relieved, as well. Hematology and blood chemistry tests were conducted before and after therapy, and patients were questioned throughout the study about possible adverse experiences. At all visits, loratadine and terfenadine were significantly superior to placebo (p less than or equal to 0.004), and the two active medications were statistically comparable, based on mean totals of sign/symptom severity scores and ratings of overall disease condition and therapeutic response. By patients' last valid visit, mean totals of sign/symptoms severity scores improved by 56% and 53% for loratadine and terfenadine groups, respectively, but exacerbated by 5% for the placebo group. Moreover, an excellent or a good therapeutic response was observed in 58/87 (67%) loratadine-treated patients and 58/89 (65%) terfenadine-treated patients, as compared to 13/80 (16%) placebo-treated patients (p less than 0.01). A total of 61/76 (30%) patients in the loratadine group and 57/78 (73%) in the terfenadine group versus 22/71 (31%) in the placebo group experienced relief within the first 3 days of therapy (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896509 TI - General pharmacology of 1-(2-ethoxyethyl)-2-(4-methyl-1 homopiperazinyl)benzimidazole difumarate. 1st communication: effects on the central nervous system. AB - Effects of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole difumarate (KB-2413) on the central nervous system were compared with those of ketotifen and chlorpheniramine. Among the various activities related to the central nervous system, KB-2413 showed inhibitory effects on locomotor activity, acetic acid-induced writhing in mice and reserpine-induced hypothermia in rats at a high dose such as 100 mg/kg p.o. However, in mice, it (10-100 mg/kg p.o.) exerted no significant influence on muscle tone, various experimental convulsions, oxotremorine-induced tremor, physostigmine-induced mortality or hexobarbital-induced sleep, and in rats, it had no effect on rectal temperature or conditioned avoidance. It also did not affect spontaneous electroencephalogram (EEG), EEG arousal responses or photic driving response in rabbits at 5 mg/kg i.v. On the other hand, ketotifen and chlorpheniramine affected more widely and strongly the central nervous system than KB-2413. In conclusion, KB-2413 showed a less potent effect on the central nervous system than ketotifen and chlorpheniramine, and no results suggested serious side effects of KB-2413. PMID- 2896510 TI - [H2-antagonistic activity of the impromidine analog, cyanoguanidine. 37. H2 antihistaminics]. AB - In studies on structure-activity relationships among impromidine-like histamine H2-receptor agonists, the synthesis of impromidine analogous guanidines led to the corresponding intermediate cyanoguanidines. The latter are structurally related to cimetidine. For that reason they were tested for H2-antagonistic activity on the isolated guinea-pig atrium. Compound 5h proved to be significantly more potent than cimetidine. Derivatives with branched thioether moiety were devoid of affinity. The results are consistent with existing structure-activity relationships. PMID- 2896511 TI - Development of AIDS, HIV seroconversion, and potential co-factors for T4 cell loss in a cohort of intravenous drug users. AB - A cohort of 334 intravenous (IV) drug users from New York City drug treatment programs were followed over a mean 9-month period. Among the 165 who were seropositive at enlistment, four developed clinical AIDS, for an annual rate of 3%. Elevated IgA was a significant predictor of developing AIDS. Among 72 subjects who were initially seronegative and who were re-interviewed, four were seropositive at follow-up, for a seroconversion rate of 7% per year among seronegatives. Among seropositive subjects who did not develop AIDS or fatal AIDS related complex (ARC), continued drug injection was associated with rate of T4 cell loss, and there was a non-significant trend for males to lose T4 cells more rapidly than females. While it was not possible to distinguish the mechanism underlying the relationship between continued drug injection and T4 cell loss, seropositive IV drug users should be warned that continued injection may lead to increased HIV-related immunosuppression as well as, if injection equipment is shared, risking viral transmission to others. PMID- 2896512 TI - A double-blind placebo controlled study of terfenadine in the treatment of chronic idiopathic urticaria. PMID- 2896513 TI - The difficult chronic asthmatic. PMID- 2896514 TI - The catastrophic asthmatic. PMID- 2896515 TI - A novel actin label: a fluorescent probe at glutamine-41 and its consequences. AB - By peptide isolation and analysis, it has been shown that the dansyl fluorophore of dansylcadaverine [N-(5-aminopentyl)-5-(dimethylamino)naphthalene-1 sulfonamide] transfers to Gln-41 of actin from rabbit skeletal muscle when the reaction is catalyzed by guinea pig liver transglutaminase. As a function of time, the degree of labeling asymptotically approaches 1 mol of dansyl/l mol of actin. About 80-85% of the attached dansyl fluorophore was found at Gln-41. Such labeled G-actin polymerizes to the same extent as control actin, but the polymerization rate is greater and the critical concentration is less than for control actin. Complete polymerization is accompanied by a 1.5-2.0-fold increase in the emission intensity of the attached fluorophore. Labeled F-actin thus obtained activates myosin subfragment 1 (S-1) Mg2+-ATPase activity with the same Kapp, and to the same Vmax, as control actin; moreover, when such labeled F-actin is cross-linked to S-1 by 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide, the resulting superactivation of Mg2+-ATPase is the same as that attained with control actin. The attributes of this label thus make it an ideal reporter of events in the N-terminal 10-kilodalton region of actin, and a new topological point for proximity mapping. PMID- 2896516 TI - A new synthesis of adenosine 5'-([gamma(R)-17O,18O]-gamma-thiotriphosphate) and its use to determine the stereochemical course of the activation of glutamate by glutamine synthetase. AB - A new synthetic route to adenosine 5'-([gamma(R)-17O,18O]-gamma-thiotriphosphate) is described which combines chemical methods for introducing the heavy oxygen isotopes and enzymic methods for achieving the enantiospecificity. This material was used as a substrate for the activation of glutamate catalyzed by glutamine synthetase from Salmonella typhimurium. Analysis of the chirality of the [16O,17O,18O]thiophosphate produced showed that the reaction proceeds with inversion of configuration on phosphorus. This result, taken together with the positional isotope exchange studies of Midelfort and Rose [Midelfort, C. F., & Rose, I.A. (1976) J. Biol. Chem. 251, 5881-5887], demonstrates that the activation of glutamate to form gamma-glutamyl phosphate proceeds by a direct "in line" transfer of the phosphoryl group. PMID- 2896517 TI - Mechanism of proline-specific proteinases: (I) Substrate specificity of dipeptidyl peptidase IV from pig kidney and proline-specific endopeptidase from Flavobacterium meningosepticum. AB - The substrate specificity of dipeptidyl peptidase IV (dipeptidyl peptide hydrolase, EC 3.4.14.5) from pig kidney and proline-specific endopeptidase from Flavobacterium meningosepticum, was investigated with a series of N-terminal unprotected (dipeptidyl peptidases IV) and succinylated dipeptidyl-p nitroanilides (proline-specific endopeptidase). Both enzymes are specific for the S configuration of the amino-acid residue in P1 and P2 position if the penultimate residue is proline. In the case of alanine substrates (Ala in P1, dipeptidyl peptidase IV hydrolyzes such compounds where the configuration of the P2 residue is R. The penultimate residue with dipeptidyl peptidase IV can be, beside proline and alanine, dehydroproline, hydroxyproline and pipecolic acid. Proline substrates (Pro in P1) with an R configuration in P2 are inhibitors of the hydrolysis of proline substrates with an S,S configuration in an uncompetitive (dipeptidyl peptide IV) or mixed inhibition type (proline-specific endopeptidase). Derivatives of Gly-Pro-pNA where the N-terminal amino group is methylated are hydrolyzed by dipeptidyl peptidase IV. PMID- 2896518 TI - Presence of D-aspartate oxidase in rat liver and mouse tissues. AB - Rat liver D-aspartate oxidase activity, which had been reported to be undetectable, was found to be well detectable in dialyzed liver homogenate. The requirements of the enzyme for activity and its sensitivity to inhibitors were identical with the known properties of the enzyme from other sources. We also demonstrated for the first time the presence of the enzyme activity in mouse tissues and some other rat tissues using dialyzed tissue homogenates. PMID- 2896519 TI - Primitive (developmental) reflexes and diffuse cerebral dysfunction in schizophrenia and bipolar affective disorder: overrepresentation in patients with tardive dyskinesia. AB - Primitive (developmental) reflexes are present in fetal and infant life, but disappear in adulthood. Their elicitation in later life usually occurs in association with cortical or diffuse cerebral dysfunction and suggests a new approach to the issue of whether tardive dyskinesia is particularly likely to occur in patients with organic brain disorder(s). Sixty-six patients with schizophrenia (age range 50-86) and 18 with bipolar affective disorder (age range 40-77) were assessed for the presence of involuntary movements and for the release of the grasp, palmomental, snout, corneomandibular, and glabellar reflexes. In each diagnostic group, patients with involuntary movements showed a significant excess of primitive reflexes in comparison with otherwise indistinguishable patients without such movements. These results complement recent reports that similar patients with involuntary movements also show greater cognitive impairment and point anew to an association between the presence of tardive dyskinesia and of organic brain dysfunction. They raise again the issue of whether or not such dysfunction may be a consequence of neurodevelopmental abnormality rather than of neurodegenerative processes. PMID- 2896520 TI - Regulation of testicular and Sertoli cell gamma-glutamyl transpeptidase by follicle-stimulating hormone. AB - Hormonal deprivation achieved by hypophysectomy or gonadotropin-releasing hormone (GnRH)-antagonist treatment of immature rats resulted in markedly lower testicular gamma-glutamyl transpeptidase (GGT) activity than in the testes of age matched controls. When begun 15 days after hypophysectomy, follicle-stimulating hormone (FSH) treatment significantly increased testicular GGT above that in testes from hypophysectomized controls in a time- and dose-dependent manner. In contrast, testosterone propionate had only a small effect. Testicular GGT was higher in adult hypophysectomized rats treated with FSH from the time of surgery than in untreated hypophysectomized rats; testosterone propionate treatment had no effect. GGT activity in Sertoli cells isolated from GnRH antagonist-treated or hypophysectomized immature rats was also lower than in cells from control rats. FSH treatment from the day of hypophysectomy resulted in Sertoli cell GGT values equivalent to those from intact controls. These data indicate that FSH regulates GGT activity in rat testis and Sertoli cells. PMID- 2896521 TI - Testicular function and Leydig cell ultrastructure in long-term bilaterally cryptorchid rams. AB - This study was conducted to investigate the effects of bilateral cryptorchidism induced in adult rams on testicular function and Leydig cell ultrastructure. The results indicated that long-term bilateral cryptorchidism resulted in decreased testicular size, degeneration of seminiferous tubules, elevated serum LH levels, maintenance of normal testosterone concentrations in peripheral and spermatic vein serum, impairment of the magnitude and duration of androgen response to exogenous luteinizing hormone (LH), a 13-fold reduction in total number of Leydig cells/paired testes, and a 3-fold hypertrophy in the average size of remaining Leydig cells. Based on quantitative morphometry, the hypertrophied Leydig cells exhibited significant increases in the volume of intracellular organelles, including the cell nucleus, mitochondria, smooth and rough endoplasmic reticulum, lysosome-like bodies and lipid vesicles. Quantitatively, the hypertrophy alone was not enough to offset the loss in number of Leydig cells and was insufficient to explain the maintenance of normal levels of testosterone in jugular and spermatic venous blood. The additional mechanisms responsible for production of normal serum testosterone levels in the cryptorchid ram remain to be elucidated. PMID- 2896523 TI - The medical therapy of reflux oesophagitis. AB - Besides changes in behaviour and lifestyle we nowadays have the choice of specific drugs in the treatment of reflux oesophagitis. A distinction can be made in motility modulating drugs, which stimulate oesophageal peristalsis and LOS pressure, mucosa-protecting drugs, which form a protective layer on the oesophageal mucosa, acid neutralizing (antacids) and acid suppressing drugs (H2 receptor antagonists, omeprazole). So far the results of medical therapy of reflux oesophagitis are still suboptimal. Giving the H2-receptor antagonists with the evening meal would possibly be more appropriate. A valid alternative is the mucosa-protecting agent sucralfate. Monotherapy will probably be insufficient for full healing, which explains why trials of combination therapy (H2-receptor antagonists plus sucralfate or plus cisapride) are being conducted. If omeprazole becomes available, it will revolutionize the therapy of severe reflux oesophagitis. Many questions (dose, duration, maintenance, safety monitoring etc.) remain to be determined. PMID- 2896522 TI - Efficiency of hemosorption in treatment of patients with ulcerative colitis. AB - One hundred and seven sessions of hemosorption were performed on 77 patients with severe ulcerative colitis. Clinically, improvement was demonstrated in the reduction of the signs of intoxication in 50 to 60 per cent of patients. Combination of hemosorption and anti-inflammatory medication allowed to achieve a remission or a marked improvement determined by clinical observation or endoscopy of 39 from 52 patients with a severe, total form of the disease, whereas toxic influence of sulfasalazine was controlled and extra-intestinal complications were weakened in 8 patients from 11. Thirteen patients were operated upon due to inefficiency of therapy. Hemosorption contributed to reduction of content of protein molecules with mean molecular weight (61 per cent), phenol (73 per cent), and endotoxin of gram-negative bacteria (50 per cent). Dynamics of acute phase reactants and humoral immune factors testifies to a weak anti-inflammatory action of hemosorption. Reduced levels of plasma protein, albumin, potassium and cholesterol were corrected or spontaneously returned to normal. PMID- 2896524 TI - Therapeutic advances in oesophageal motility disorders. PMID- 2896525 TI - Experience in the control of khat-chewing in Somalia. AB - The chewing of the leaves of the plant called khat (Catha edulis Forsk) is a common habit in some countries of East Africa and the Arabian Peninsula. Khat chewing has a stimulating effect on the central nervous system, which is the reason for the widespread abuse of this plant. From the mid-1960s to the early 1980s, khat-chewing spread from the limited area of the north-western part of Somalia to the whole country, assuming epidemic proportions. Khat-chewing was recognized as a real national problem with adverse consequences for the health and socio-economic development of the country. A law prohibiting the use, importation, cultivation and trade of khat was enacted in 1983, and it has been strongly enforced by a comprehensive national programme that has mobilized the whole country to achieve its objectives. Committees to co-ordinate action on khat control were established at the national, regional and local levels. An information and education campaign through the use of the mass media has been carried out to support the national programme. After the successes achieved in the enforcement of the prohibition law, the national authorities, hampered by a shortage of financial resources, have had major difficulties in providing farmers with adequate compensation for damage caused to them by the destruction of khat plantations. Difficulties were also experienced in coping with the unemployment of those who were involved in the khat business and in establishing the recreational facilities needed to provide healthy social alternatives to khat chewing sessions. These difficulties have only been partly solved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896526 TI - Hypnotic drug use among the elderly. PMID- 2896527 TI - Motor disturbances and neurotoxicity induced by centrally administered somatostatin and vasopressin in conscious rats: interactive effects of two neuropeptides. AB - Barrel rotation (BR) is an abnormal, long-axis rotation induced by intracerebroventricular (i.c.v.) injections of peptides, including somatostatin (SRIF) and arginine-vasopressin (AVP). This study examined the effects of two i.c.v. doses of SRIF and combined injections of SRIF and AVP in conscious, adult Wistar and Sprague-Dawley rats. Mortality after i.c.v. SRIF was dose-dependent; 0/16 rats died after a 20 microgram dose, while 21/43 died after 40 micrograms SRIF. On the other hand, BR incidence was similar after the two doses, but the hazard function of the BR latency data was shifted to the left by the higher dose. Although the incidence data imply that BR and mortality are independent, the hazard function of BR latency data is predictive of mortality. An interaction study employing a combined i.c.v. dose of 20 micrograms SRIF and 0.5 micrograms AVP established that the effects add non-linearly. This is illustrated by a marked increment in mortality (0/16 for 20 micrograms SRIF, 1/25 for 0.5 micrograms AVP and 12/18 for SRIF + AVP). The hazard plot shows a similar, non linear interaction. In addition, SRIF, but not AVP, produced a characteristic pattern of Purkinje cell death in cerebellar regions projecting to the fastigial and lateral vestibular nuclei. These results imply that SRIF and AVP act at independent sites to produce BR and mortality, and that the effects summate non linearly at a common central site. This raises the issue of whether these neuropeptides, endogenous in human CSF, interact to produce similar biological effects. PMID- 2896528 TI - Excitatory amino acid antagonists depress acoustic startle after infusion into the ventral nucleus of the lateral lemniscus or paralemniscal zone. AB - Rats were implanted with bilateral cannulas in an area just medial to the ventral nucleus of the lateral lemniscus, an obligatory relay along the acoustic startle pathway. Bilateral infusions of excitatory amino acid transmitter antagonists into this region (10, 25 or 50 nmol per side) produced a rapid, dose-dependent depression of acoustic startle. gamma-D-Glutamylglycine, gamma-D glutamylaminomethyl sulfonate and 2-amino-5-phosphonovalerate were equally effective in depressing the startle response over this dose range. These results indicate that excitatory amino acid transmitters play an important role in the expression of acoustic startle at this part of the startle pathway. PMID- 2896529 TI - Retrograde changes in transglutaminase activity after peripheral nerve injuries. AB - It has been previously demonstrated that transglutaminase activity in rat superior cervical ganglion is rapidly and transiently increased minutes after nerve injury. The present series of experiments sought to determine: (1) whether or not similar changes are expressed by other peripheral neuronal systems, and (2) if injury-induced changes in the enzyme activity can be detected along the injured nerve, and if so do they occur in axons or in non-neuronal cells. In the nodose ganglion transglutaminase activity increased (approximately 40%) 48 h after the vagus nerve was crushed 25 mm from the ganglion. In the vagus nerve the activity was transiently increased (approximately 100%) within 1 h, followed by a second increase (approximately 140%) after 3 h. This occurred only in the proximal nerve stump close to the injury site and not in the section of nerve closer to the ganglion. Comparable enzyme activity was found in unoperated vagus nerve and in distal stumps of previously ligated vagus nerves. In dorsal root ganglia no changes were found for up to 24 h after the sciatic nerve was crushed 40 mm from the ganglion. In the facial nucleus a transient increase was observed after the facial nerve was crushed about 14 mm distally with a peak (approximately 300) at 3 days and a decline within 14 days. A second lesion of the facial nerve made 12 days following a conditioning lesion led to a rebound of enzyme activity in the facial nucleus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896530 TI - Anatomical and electrophysiological characterization of presumed dopamine containing neurons within the supramammillary region of the rat. AB - A combination of immunocytochemical, electrophysiological and pharmacological techniques were employed to study the properties of neurons within the supramammillary (SUM) complex of the rat. The SUM region contains a small, but dense, population of tyrosine hydroxylase immunoreactive neurons. Following injection of the orthograde neuroanatomical tracer, Phaseolus Vulgaris leucoagglutinin, into the SUM region, heavy terminal labeling was observed in the lateral septal nucleus, diagonal band of Broca and bed nucleus of the stria terminalis. The electrophysiological and pharmacological properties of antidromically-activated SUM neurons revealed evidence of two neuronal populations. Both groups of neurons exhibited long duration action potentials (greater than 2 msec) and slow conduction velocities (less than 0.5 m/sec). However, cells in one group were characterized by slow and erratic firing rates and insensitivity to dopamine (DA) autoreceptor agonists. Cells in the other group typically exhibited no spontaneous activity but could be induced to discharge by iontophoretic application of glutamate. These latter cells were sensitive to DA autoreceptor stimulation. Of the two populations of mammilloseptal SUM neurons, the silent population exhibited several properties similar to those of midbrain DA neurons. PMID- 2896531 TI - Xenografts of mouse hippocampal tissue. Exchange of laminar and neuropeptide specific nerve connections with the host rat brain. AB - Immature hippocampal and fascia dentata tissue from embryonic and newborn C57 mice was grafted to the hippocampal region of newborn Kyoto rats. The age of the donor mice varied from embryonic day 13 to the day of birth, and the recipient rats from the day of birth up to 2 days. After survival times of from 5 weeks to 1 year the recipient brains were histologically processed for the tracing of host xenograft connections by silver staining and electron microscopy of anterograde degeneration, AChE histochemistry, immunohistochemical demonstration of the neuropeptides CCK and enkephalin, and the histochemical Timm sulphide silver method, as well as stained by ordinary cell and fiber stains. The survival of the xenografts depended on the donor age, with less than 10% survival for newborn donors and 60-69% for E13-16 donors. The surviving xenografts developed an organotypic organization and retained a mouse-specific CCK-reactivity in the associational hilodentate system and the dentate mossy fibers. Judged by their positive AChE histochemistry most xenografts received a host rat cholinergic projection when placed in normal cholinoreceptive areas, including areas outside the normal reach of the septo-hippocampal system like the neocortex. Xenografts encroaching on the trajectory of the host rat commissural and perforant path projections or their terminal fields in fascia dentata received laminar and neuropeptide specific host projections. Electron microscopy of host rat perforant path fibers traced to the xenograft dentate molecular layer confirmed the laminar distribution and revealed numerous asymmetric synaptic contacts with spines. An efferent xenograft projection of CCK-reactive mouse mossy fibers into the host CA3 mossy fiber layer demonstrated that this cross-species, mouse to rat innervation also applied to the normal developmental rules, despite the, for the rat abnormal, CCK-content. The formation of laminar and neuropeptide specific mouse-rat nerve connections demonstrates the potentials of intracerebral neuronal grafting in basic and applied neurobiological research by providing new experimental models for the analysis of developmental and functional interactions between nerve cells. PMID- 2896532 TI - Thermally-induced activities of the mesencephalic reticulospinal and rubrospinal neurons in the rat. AB - Unit activities of 226 midbrain reticulospinal (mRfS) and non-mRfS neurons and 238 rubrospinal (RbS) and non-RbS neurons were investigated during changes in temperatures of midbrain (Tmb), preoptic and anterior hypothalamus (Thyp) and skin (Ts) in the urethane-anesthetized rat. Responsiveness to Tmb, Thyp and Ts were found in 43.5%, 41.6% and 51.5% of neurons of midbrain reticular formation (mRf), and in 35.2%, 32.7% and 17.6% of neurons of red nucleus (Rb). Higher incidence of responsiveness to remote temperatures was found among Tmb responsive neurons than Tmb unresponsive neurons in both mRf and Rb. The mRf contains significantly greater numbers of neurons having such multiple thermal responsiveness and also of neurons which were activated by falls in temperatures (cold-responsive neurons) than the Rb. These characteristics were more conspicuously seen among mRfS neurons, showing a high degree of convergence of cold signals from different sites of body. On the other hand, RbS neurons did not differ from non-RbS neurons regarding thermal characteristics and showed no particular combinations of responsiveness to temperatures of different sites. Microinjection of procaine and glutamate into the mRf just dorsolateral to the Rb, but not into the Rb, decreased and increased cold-induced increase in EMG activity and shivering without changes in cardiovascular and respiratory parameters and pilomotor activity. The results suggest that mRfS neurons are involved in the control of thermoregulatory muscle tone and shivering. PMID- 2896533 TI - Comparison of adrenal medullary, carotid body and PC12 cell grafts in 6-OHDA lesioned rats. AB - The survival and functional properties of dispersed cell implants of catecholaminergic cells obtained from the peripheral nervous system of adult rats (adrenal medulla and carotid body glomus cells) and PC12 cells from a rat pheochromocytoma cell line were examined following transplantation into the striatum of the adult rat. The host animals, all with unilateral 6 hydroxydopamine (6-OHDA) nigrostriatal lesions, were divided into 5 groups: (1) PC12 cells transplanted into Cyclosporin-A treated hosts; (2) PC12 cell grafts into hosts without Cyclosporin-A treatment; (3) grafts of adrenal medullary cells; (4) grafts of glomus cells; and (5) vehicle controls. All animals were sacrificed one month after transplantation. Immunocytochemical staining for tyrosine hydroxylase, the rate-limiting enzyme for catecholamine synthesis, was used to identify and characterize the grafted cells. PC12 cells were detected in four of six Cyclosporin-A treated rats, and two of these grafts developed into tumors. However, only one of the six non-Cyclosporin-A treated hosts was found to have surviving PC12 cells, and none of these rats developed tumors. No significant differences in rotational behavior were seen in either of the PC12 cell recipient groups. Grafted cells could be identified in all of the adrenal medullary and glomus cell recipients. However, the number of surviving cells was quite limited, with not more than 100 tyrosine hydroxylase-positive grafted cells found in any one recipient. Tyrosine hydroxylase-positive fibers were present adjacent to the transplants in these latter graft recipients, but the fibers appeared to be of host origin rather than from the grafts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896535 TI - Characteristics of beta-adrenoceptors in tracheal smooth muscle of guinea pig sensitized by egg albumin. AB - The effect of pretreatment with egg albumin was examined on the beta adrenoceptors in guinea pig isolated trachea. Befunolol and carteolol acted as partial agonists and their pA2 values were significantly larger than their corresponding pD2 values in tracheae from both untreated guinea pigs and those treated with egg albumin, suggesting that the beta-adrenoceptors contain two different affinity sites. The Scatchard plot of specific [3H]befunolol binding showed two affinity sites of the receptor (high and low affinity sites) in tracheae from both untreated animals and those treated with egg albumin. The pKD values of befunolol for both low and high affinity sites were in agreement with their respective pD2 and pA2 values. The intrinsic activities of befunolol and carteolol and the pD2 values of the test drugs were decreased by the treatment with egg albumin. The treatment with egg albumin also decreased the total amount of the two affinity sites of the receptor without any change in affinity. The present results support the partial blockade of beta-adrenoceptors in asthma proposed by Szentivanyi. PMID- 2896534 TI - Contributions of benzodiazepines to cancer therapy. AB - We have reviewed the therapeutic effects of benzodiazepines employed as adjuncts to cancer treatment. These agents have been used primarily for alleviating or attenuating situational anxiety, insomnia, chemotherapy-induced nausea and vomiting, and anticipatory nausea and vomiting. Situational anxiety not corrected by psychosocial support, symptom control, or time may be successfully treated with benzodiazepines. Procedure-related anxiety, for example, that related to bone marrow biopsy, venipuncture, intrathecal therapy, and the insertion of subclavian and femoral catheters, is a serious problem that may be alleviated by the use of benzodiazepines. Insomnia not caused by a depression serious enough to warrant treatment with a tricyclic antidepressant also may be successfully treated with benzodiazepines. Many clinicians have found benzodiazepines to be useful adjuncts to a cancer chemotherapy regimen because of their anxiolytic, sedative, and amnesic properties and also because of their suspected antiemetic properties when these drugs are used in conjunction with known antiemetic agents. The ability of lorazepam to induce antegrade amnesia has proved particularly useful in alleviating anticipatory nausea and vomiting connected with repeated courses of cytotoxic chemotherapy. Furthermore, since benzodiazepines are relatively safe drugs, their continued and probably expanded uses as cancer therapy adjuncts can be anticipated. PMID- 2896536 TI - Supersensitivity to norepinephrine in chronically denervated kidneys: evidence for a postsynaptic effect. AB - Denervation supersensitivity in chronically denervated kidneys increases renal responsiveness to increased plasma levels of norepinephrine. To determine whether this effect is caused by presynaptic (i.e., loss of uptake) or postsynaptic changes, we studied the effect of continuous infusion of norepinephrine (330 ng/min, i.v.) and methoxamine (4 micrograms/min, i.v.), an alpha 1-adrenergic agonist that is not taken up by nerve terminals, on renal function of innervated and denervated kidneys. Ganglionic blockade was used to eliminate reflex adjustments in the innervated kidney and mean arterial pressure was maintained at preganglionic blockade levels by an infusion of arginine vasopressin. With renal perfusion pressure controlled there was a significantly greater decrease in renal blood flow (-67 +/- 9 vs. -33 +/- 8%), glomerular filtration rate (-60 +/- 9 vs. 7 +/- 20%), urine flow (-61 +/- 7 vs. -24 +/- 11%), sodium excretion (-51 +/- 15 vs. -32 +/- 21%), and fractional excretion of sodium (-50 +/- 9 vs. -25 +/- 15%) from the denervated kidneys compared with the innervated kidneys during the infusion of norepinephrine. During the infusion of methoxamine there was a significantly greater decrease from the denervated compared with the innervated kidneys in renal blood flow (-54 +/- 10 vs. -30 +/- 14%), glomerular filtration rate (-51 +/- 11 vs. -19 +/- 17%), urine flow (-55 +/- 10 vs. -39 +/- 10%), sodium excretion (-70 +/- 9 vs. -59 +/- 11%), and fractional excretion of sodium (-53 +/- 10 vs. -41 +/- 10%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896537 TI - Effects of beta-adrenergic agonist infusions on myometrial activity and plasma prostaglandin levels in the nonpregnant sheep. AB - Recent studies have reported that beta-adrenergic agonists stimulate the production of stimulatory prostaglandins (PGs) by intrauterine tissues in vitro. These drugs are used clinically to inhibit uterine contractions; consequently an increase in stimulatory PGs in vivo might have potentially adverse effects. We have, therefore, investigated whether beta-adrenergic agonists increase plasma PG concentrations in vivo. Samples of peripheral (aorta) and uterine venous enriched (vena cava) blood from nonpregnant sheep were collected at 15-min intervals for 1 h before, 3 h during, and 1 h postinfusion of either (a) the beta-adrenergic agonist isoproterenol (Isop) at a dose of 0.16 microgram.kg-1.min-1; (b) Isop at a dose of 0.08 microgram.kg-1.min-1; or (c) saline, 1 mL/h via a jugular vein catheter. The sheep were also equipped with intrauterine recording balloons to record intrauterine pressure and myometrial electromyographic (EMG) electrodes to measure EMG activity. Infusion of Isop at 0.16 microgram.kg-1.min-1 produced a significant initial inhibition of uterine activity, although contractions returned (within 60 min) despite continued administration of Isop. Plasma PGE2 (but not PGF2 alpha or 13,14-dihydro-15-keto-PGF2 alpha (PGFM] concentrations were significantly elevated during the Isop infusion. Administration of Isop at 0.08 microgram.kg-1.min-1 produced no effects on uterine contractile activity but was associated with a significant elevation in plasma PGE2 (but not PGF2 alpha or PGFM) concentrations. No changes in plasma PGE2, PGF2 alpha, or PGFM occurred during saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896538 TI - Characteristics of phorbol ester stimulated growth hormone release: inhibition by insulin-like growth factor I, somatostatin, and low calcium medium and comparison with growth hormone releasing factor. AB - TPA (12-O-tetradecanoylphorbol 13-acetate) is one of a class of compounds known as tumor promoters which perturb the inositol phosphate pathway in a number of cells. We have used TPA in a dispersed rat adenohypophysial cell system to probe the characteristics of growth hormone (GH) release. In this system we have found that the cells release GH in response to low concentrations of TPA: the EC50 was 0.23 +/- 0.05 nM (n = 6) and the maximal concentration was 5 nM. However, the maximal TPA-induced GH release was only 34 +/- 5% (n = 7) of the GH released by maximal growth hormone releasing factor (GRF) suggesting TPA releases a subpool of stored GH. Both somatostatin and insulin-like growth factor I inhibit GH release stimulated by TPA to the same extent as that stimulated by GRF, showing that the normal inhibitory control mechanism of release is not altered. Incubation in a low calcium medium that totally blocks GRF-stimulated GH release also inhibits TPA-stimulated GH release. The calcium channel blockers nifedipine and diltiazem both partly inhibit GRF- and TPA-stimulated GH release, showing some component of the calcium necessary for GH release arises from influx across the cell membrane. PMID- 2896539 TI - Prejunctional alpha 2-adrenergic properties of S-3341 (dicyclopropylmethyl)amino 2-delta-2-oxazoline: a comparison with clonidine. AB - The prejunctional activities of S-3341 and clonidine have been studied in the transmural field-stimulated epididymal part of the rat vas deferens. Both S-3341 and clonidine inhibited these neuronally induced contractions. At high concentrations, these agonists induced spontaneous contractions in the preparation, which were abolished by 10(-7) M prazosin. The inhibitory effects of S-3341 and clonidine were antagonized in a competitive manner by rauwolscine and were found not to be modified in a statistically significant manner by 10(-7) M prazosin. The pA2 values of rauwolscine against S-3341 and clonidine were the same, indicating the receptors influenced by these drugs were the same also. However, the efficacy of S-3341 is lower than that of clonidine (by a factor of approximately 100). This lower efficacy of S-3341 at the prejunctional level could be linked to the lack of a sedative effect of this compound at therapeutic concentrations. PMID- 2896541 TI - Characterization of a monoclonal antibody reacting with a neutral glycolipid that is associated with human T-cell leukemia virus type I infection and freshly isolated adult T-cell leukemia. AB - During attempts to make antibodies cross-reactive with human lymphocytes, we established a monoclonal antibody (VJ-41) from the alloimmunization of mice, that is, B10.A(3R) anti-B10.A(5R). VJ-41 reacted with all cases of freshly isolated adult T-cell leukemia cells (36 cases) but not with cells from other hematological disorders (more than 50 cases). Human T-cell leukemia virus Type I healthy carriers also seemed to possess these VJ-41 antigen positive cells. However, in vitro established adult T-cell leukemia cell lines did not show the reactivity with VJ-41. Normal lymphocytes from humans or mice apparently did not carry this antigen, but mitogen activated lymphocytes or some in vitro maintained malignant cell lines of both human and mouse origins showed positive reaction. Having established solid phase radioimmunoassay to detect the VJ-41 antigen in plasma, it was found that healthy human T-cell leukemia virus Type I carriers, but not the majority of adult T-cell leukemia patients, predominantly possessed this antigen. Even though immunochemical characterizations of cellular materials were unsuccessful, a certain neutral glycolipid was detected from healthy human T cell leukemia virus Type I carrier plasma by using thin-layer chromatography and immunostaining with the VJ-41 antibody. PMID- 2896540 TI - High-resolution studies of chromosome 10 in 23 MEN-2 families. PMID- 2896542 TI - [Personalized therapy of arterial hypertension: problems of clinical implementation]. PMID- 2896543 TI - [Personalized therapy of arterial hypertension: problems of clinical implementation]. PMID- 2896544 TI - Long term chronic D-amphetamine-induced histobiochemical alterations of GD and AAT enzymatic activities in the rat cerebellum. PMID- 2896545 TI - [The importance of precordial ECG mapping in patients with anterior myocardial infarct]. PMID- 2896546 TI - Peroxisomes in intestinal and gallbladder epithelial cells of the stickleback, Gasterosteus aculeatus L. (Teleostei). AB - The occurrence of microbodies in the epithelial cells of the intestine and gallbladder of the stickleback, Gasterosteus aculeatus L., is described. In the intestine the organelles are predominantly located in the apical and perinuclear zone of the cells and may contain small crystalline cores. In gallbladder epithelial cells the microbodies are distributed randomly. The latter organelles are characterized by the presence of large crystalloids. Cytochemical and biochemical experiments show that catalase and D-amino acid oxidase are main matrix components of the microbodies in both the intestinal and gallbladder epithelia. These organelles therefore are considered peroxisomes. In addition, in intestinal mucosa but not in gallbladder epithelium a low activity of palmitoyl CoA oxidase was detected biochemically. Urate oxidase and L-alpha hydroxy acid oxidase activities could not be demonstrated. PMID- 2896547 TI - [An analysis of factors concerning an outbreak of epidemic hemorrhagic fever occurring in the forest region of Xiao Xing-An-Ling]. PMID- 2896548 TI - The yeast regulatory gene PHO2 encodes a homeo box. PMID- 2896549 TI - Dynamics of a fluorescent calmodulin analog in the mammalian mitotic spindle at metaphase. AB - We have compared the exchange kinetics of fluorescein-labeled calmodulin and tubulin in the spindles of living mitotic cells at metaphase. Cultured mammalian cells in early stages of mitosis were microinjected with labeled calmodulin or tubulin and returned to an incubator to allow equilibration of the fluorescent protein with the endogenous protein pools. Calmodulin becomes concentrated in the mitotic spindle, and treatments with inhibitors of tubulin assembly show that this concentration is dependent on the presence of microtubules. The steady-state exchange rates of both tubulin and calmodulin were measured by an analysis of fluorescence redistribution after photobleaching (FRAP), using cells pre equilibrated to either 26 +/- 2 degrees C or 36 +/- 2 degrees C. A pulse of laser light focused to a 5-microns diameter column was used to destroy the fluorescence at one pole of a metaphase mitotic spindle. Ratios of fluorescence intensity from the two half-spindles and from the two polar regions were calculated for each image in a post-bleach time series to determine the rates and extents of FRAP. For tubulin, we confirm earlier observations concerning the temperature dependence of the extent of FRAP, but our data do not show a significant temperature dependence for the rate of FRAP. We hypothesize that the reduced extent of tubulin FRAP at the lower temperatures is a result of microtubules that are stable to depolymerization at 26 degrees C and are thus less likely to exchange subunits. Calmodulin's FRAP, however, does not exhibit any of the temperature dependence observed with fluorescent tubulin. At 26 +/- 2 degrees C calmodulin exchanges rapidly with the relatively stable population of microtubules, suggesting that calmodulin is bound, either directly or indirectly, to microtubule walls. PMID- 2896551 TI - [Psychopharmaceuticals as instruments for research]. PMID- 2896552 TI - [Changes in gamma-glutamyltransferase activity of the amniotic fluid in fetuses with severe disorders of prenatal development]. PMID- 2896550 TI - Sequence analysis of cDNAs for the human and bovine ATP synthase beta subunit: mitochondrial DNA genes sustain seventeen times more mutations. AB - We have cloned and sequenced human and bovine cDNAs for the beta subunit of the ATP synthase (ATP-syn beta), a nuclear DNA (nDNA) encoded oxidative phosphorylation (OXPHOS) gene. The two cDNAs were found to share 99% amino acid homology and 94% nucleotide homology. The evolutionary rate of ATPsyn beta was then compared with that of two mitochondrial DNA (mtDNA) ATP synthase genes (ATPase 6 and 8), seven other mtDNA OXPHOS genes, and a number of nuclear genes. The synonymous substitution rate for ATPsyn beta proved to be 1.9 x 10(-9) substitutions per site per year (substitutions x site-1 x year-1) (SSY). This is less than 1/2 that of the average nDNA gene, 1/12 the rate of ATPase 6 and 8, and 1/17 the rate of the average mtDNA gene. The synonymous and replacement substitution rates were used to calculate a new parameter, the "selective constraint ratio". This revealed that even the most variable mtDNA protein was more constrained than the average nDNA protein. Thus, the high substitution mutation rate and strong selective constraints of mammalian mtDNA proteins suggest that mtDNA mutations may result in a disproportionately large number of human hereditary diseases of OXPHOS. PMID- 2896553 TI - Glutathione mutagenesis in Salmonella typhimurium is a gamma glutamyltranspeptidase-enhanced process involving active oxygen species. AB - Reduced glutathione (GSH) is mutagenic in Salmonella in the presence of gamma glutamyltranspeptidase (GGT), with the highest response obtained in strain TA102. Reduced cysteinylglycine, one of the products of GGT metabolism of GSH, is mutagenic in the absence of GGT. In strain TA102, GSH mutagenesis was dependent on molecular oxygen, enhanced by iron, inhibited by EDTA, desferrioxamine mesylate, mannitol, butylated hydroxyanisole, peroxidase and catalase, but not by superoxide dismutase. Binding of GSH or its GGT-dependent metabolites to DNA in vitro was not detected. This is consistent with a model of an indirect mechanism of mutagenesis, i.e. cleavage of GSH by GGT, followed by facile auto-oxidation of the resulting cysteinylglycine, with the production of free radicals which lead to the (pen)ultimate mutagen, H2O2. PMID- 2896555 TI - The dose in humans at which ICI 118,551 (a selective beta 2-adrenoceptor blocking agent) demonstrates blockade of beta 1-adrenoceptors. AB - The effects of four single oral doses of ICI 118,551 (a selective beta 2 adrenoceptor blocking agent: doses 10, 20, 50, and 100 mg) have been compared with placebo in five normal, healthy volunteers on some cardiovascular responses to intravenous infusions of dobutamine. Increasing infusions of dobutamine produced reproducible dose-dependent reductions in systolic time intervals and increases in systolic blood pressures, these responses representing positive inotropic effects of dobutamine. These effects of dobutamine were unaffected 2 hours after administration by 10 mg ICI 118,551 and minimally by 20 mg; the 50 mg dose attenuated the systolic time interval effect whereas the 100 mg dose attenuated further the systolic time interval reduction and also the increase in systolic blood pressure. These results allow a conclusion that at unit doses of 50 mg and above, ICI 118,551 will produce demonstrable effects on beta 1 adrenoceptors. PMID- 2896554 TI - Systemic adrenaline attenuates skin response to antigen and histamine. AB - Six atopic subjects received either adrenaline (0.3 ml of 1 mg/ml), subcutaneously over the deltoid muscle, or saline on 2 separate days. After 10 min, histamine and antigen were injected intradermally in the forearm. Adrenaline significantly inhibited the flare of histamine and both the flare and weal of antigen (P less than 0.05). This anti-allergic action of adrenaline occurred with a dose that we have previously shown produces plasma concentrations at the upper limit of the physiological range in resting normal subjects. PMID- 2896557 TI - Comparative study of high bio-availability glaphenine and paracetamol in cervical and lumbar arthrosis. AB - Seventy-eight patients, 40 suffering from cervical arthrosis and 38 from lumbar arthrosis, received for a period of two weeks paracetamol or a new preparation of glaphenine, in a double blind study. The two drugs were found to have the same efficiency on the subjective parameters but high bioavailability glaphenine seems to have an effectiveness in the range of articulatory movements, which is not found with paracetamol. The side effects were quite equivalent. PMID- 2896556 TI - Epinephrine and left ventricular function in humans: effects of beta-1 vs nonselective beta-blockade. AB - Changes in cardiac performance in response to epinephrine administered by graded infusion were assessed by M-mode echocardiography in normotensive healthy subjects after pretreatment with placebo, the beta 1-selective blocker atenolol, or the nonselective beta-blocker propranolol. Epinephrine alone increased heart rate and left ventricular end diastolic dimension and decreased left ventricular end systolic dimension. Left ventricular performance as assessed by fractional shortening and systolic blood pressure/end-systolic volume (P/V) ratio was also increased. Atenolol pretreatment did not significantly affect the increase in heart rate by epinephrine. However, atenolol did prevent the effects of epinephrine on left ventricular dimensions and left ventricular performance at the lower infusion rates and significantly blunted these effects at the highest infusion rate. After propranolol, epinephrine significantly decreased left ventricular end diastolic dimension despite decreasing heart rate and left ventricular emptying (associated with a high afterload). P/V ratio remained unchanged. These results indicate that beta 2-receptors may play a major role in the increase in heart rate caused by epinephrine. In contrast, epinephrine's positive inotropic effect appears to be mediated primarily via beta 1-receptors and, at higher concentrations, possibly also through beta 2-receptors. The pattern of changes in left ventricular end diastolic dimension suggests that epinephrine increases venous return via both beta 1- and beta 2-receptor stimulation and that alpha-receptor stimulation (epinephrine after propranolol) may actually decrease venous return. PMID- 2896559 TI - Comparison of famotidine with cimetidine and ranitidine. AB - The pharmacodynamic, therapeutic, and toxicologic properties of famotidine are evaluated and compared with those of cimetidine and ranitidine. Famotidine, an H2 receptor antagonist with a thiazole nucleus, is approximately 7.5 times more potent than ranitidine and 20 times more potent than cimetidine on an equimolar basis. Therapeutic trials indicate that famotidine 20 mg b.i.d. or 40 mg at bedtime is as effective as standard doses of cimetidine and ranitidine for healing duodenal ulcers. A dose of 40 mg at bedtime appears to heal benign gastric ulcers. A single nocturnal dose of 20 mg is effective in preventing duodenal ulcer relapse. Further studies are required that compare the efficacy of famotidine with cimetidine and ranitidine in the treatment of gastric ulcers and in the prevention of recurrent duodenal ulcers. The overall incidence of adverse effects observed with famotidine appears to be similar to that reported for cimetidine and ranitidine. Like ranitidine, famotidine does not have antiandrogenic effects or substantially inhibit the hepatic metabolism of drugs. Because of its increased antisecretory potency and lack of antiandrogenic effects at higher doses, famotidine may be the H2-receptor antagonist of choice in treating Zollinger-Ellison syndrome. Additional clinical experience, as well as cost and safety factors, will determine the place of famotidine in treating and preventing acid-peptic disorders. PMID- 2896560 TI - Prostacyclin-inhibition of lysine accumulation by the rat left ventricle. AB - 1. Left ventricular slices of male Sprague-Dawley rats were incubated with a fixed concentration of 0.5 microCi/ml 3H-lysine and several concentrations of unlabelled lysine ranging from 0.2 to 5.0 mM in control and prostacyclin-treated experiments. The time of incubation ranged from 0.5 to 90 min. 2. Left ventricular slices were cut to have an optimal thickness of 0.47 +/- 0.09 mm. 3. Lysine was taken up against a concentration gradient. Saturation was reached at 0.5 mM and steady state accumulation of lysine was attained within 60 min. 4. Prostacyclin in concentrations ranging from 1.2 x 10(-8) to 4.8 x 10(-8) M inhibited lysine transport in left ventricular slices significantly (P less than 0.01). PMID- 2896558 TI - T lymphocytes in ankylosing spondylitis and the influence of sulphasalazine treatment. AB - Twenty-nine patients with ankylosing spondylitis (AS) were studied in an attempt to evaluate the role of T lymphocytes in this disease and a possible influence of treatment. The proportions of various T cell subpopulations in blood were assessed with monoclonal antibodies. Before treatment the proportions of Leu-4+ cells and Leu 3a+ cells were decreased while Leu-2a+ lymphocytes appeared in normal proportions. Leu-7+ cells appeared in increased proportions. An increased proportion of Leu-M1 positive cells were identified in the lymphocyte preparation from the patients, possibly reflecting the presence of activated granulocytes. Activation of the different cell types was studied with double staining technique. No activated Leu-3a+ or Leu-2a+ lymphocytes were present in blood when the patients were analyzed as one group, but when divided into subgroups according to inflammatory activity, the highest levels of activated Leu-2a+ lymphocytes were found in the group with active disease. Functional assays measuring DNA synthesis of T and B cells were normal. After three months treatment with sulphasalazine the patients showed clinical and laboratory improvement. The proportion of activated Leu-2a+ cells decreased during treatment, but no other changes occurred in the lymphocyte markers or lymphocyte functional tests. A patient control group showed no clinical improvement nor any changes in T cell markers. Our results support the concept that AS is a disease which affects the lymphocyte system and that the improvement induced by sulphasalazine may involve actions on this system. PMID- 2896561 TI - Concentrations of ketone bodies in the blood of the green lizard Ameiva ameiva (Teiidae) in different physiological situations. AB - 1. The concentrations of acetoacetate and 3-hydroxybutyrate have been determined in the blood of the green lizard Ameiva ameiva (Teiidae) in fed animals and in animals starved for periods from one week to about four months. 2. The concentrations of acetoacetate are low and unaltered in fed and starved animals, being in the range from 0.014 to 0.018 mM. 3. The concentrations of 3 hydroxybutyrate are high: 2.67 mM, in fed animals, falling during starvation down to 0.26 mM. 4. The 3-hydroxybutyrate/acetoacetate ratio is high, 151, in fed animals, falling down to 17. 5. The possible importance of ketone bodies in the metabolism of Ameiva ameiva is discussed. PMID- 2896562 TI - Haematological and blood biochemical studies in female domesticated Indian elephants (Elaphas maximus L.). AB - 1. Some haematological and biochemical blood parameters in female Indian elephants were investigated. 2. Haematological data were as follows: Ht = 39.2 +/ 2.36%, Hb = 10.1 +/- 0.54 g%, RBC = 2.66 +/- 0.32 x 10(6)/mm3, WBC = 5.43 +/- 0.48 x 10(3)/mm3. Lymphocytes, determined on blood smears were mainly leucocytes from (67.0 +/- 1.59%). Data for MCV, MCH and MCHC are also given. 3. Blood plasma was separated into 5 main fractions, total plasma protein concentration was 6.98 +/- 0.53 g%, A/G ratio was 0.69 +/- 0.1. 4. Plasma minerals concentration was as follows: Na, 3044 +/- 194 micrograms/ml; K, 529 +/- 38.5 micrograms/ml; Mg, 33.0 +/- 3.43 micrograms/ml; Ca, 181.0 +/- 17.8 micrograms/ml; InP, 44.6 +/- 6.1 micrograms/ml. Ca: P ratio was 3.25 +/- 0.34. 5. Some seasonal differences in investigated parameters were observed. Ht values, WBC and neutrophils number as well as Ca, and Mg concentrations were higher during winter, whereas RBC and Na and InP concentrations were lower in winter. PMID- 2896563 TI - The absorption of free and "peptide" amino acids in the small intestine of chicks. AB - 1. The accumulation of free L-tryptophan and glycine in the small intestine of chicks, as well as of amino acids released at the hydrolysis of glycyl-L tryptophan, glycyl-L-leucine and glycyl-L-valine, was studied under experiments in vitro with accumulating preparations of chicks intestinal mucosa. 2. At the incubation of accumulating mucosal preparations (AMP) in a medium containing the investigated compounds in the presence of sodium ions (140 mM) or an equal amount of potassium ions, the existence of 2 ways of their transport was found: sodium independent and sodium-dependent. The latter is decisive for the transport of free L-tryptophan. 3. In the case of peptide L-tryptophan the power of both mechanisms is about the same, but in case of free glycine the sodium-independent mechanism is dominant. 4. The transport of peptide glycine is realized only through the sodium-independent mechanism. 5. The existence of amino acid transport against the gradient is noted by replacing sodium by potassium ions in the incubation medium. Its absence was observed at the incubation of AMP under anaerobic conditions. 6. The study of kinetics of L-tryptophan accumulation showed that the replacement of sodium ions by potassium ones in the incubation medium is accompanied by a decrease of Kt from 2.23 to 0.84 mM as well as of V from 4.54 to 0.84 mM/min per cm. 7. Modifiers (L-valine, L-threonine, L-alpha alanine) in concentrations of 100 mM inhibit drastically the accumulation of free and peptide L-tryptophan in the mucosa of chick small intestine, and this effect is mainly related to the action of sodium-dependent transport mechanisms. PMID- 2896564 TI - Effect of changes in scrotal temperature on food intake in pigs. AB - 1. Temperature of the scrotum or a similarly sized area of skin on the back of young pigs was changed by means of a thermal pad and food intake was measured. 2. Warming the scrotum to 42 degrees C significantly increased food intake in pigs reared and fed at 25 degrees C. 3. Cooling the scrotum to 20 degrees C, or changing the back skin temperature had no effect on food intake. 4. Acclimation to 10 degrees C, or exposure to 10 degrees C for 4 hr before a meal resulted in an increase in food intake. 5. Warming the scrotum did not affect this cold induced increase in food intake. Warming the scrotum, but not the skin on the back, reversed the meal-induced increase in rectal temperature. 6. It is concluded that changes in food intake observed during warming the scrotum were not a direct result of the sensory information signalling increased skin temperature. 7. The likely mechanisms involved are the interactions of peripheral and deep body temperature, decreased deep body temperature and increased heat loss. PMID- 2896565 TI - Muscle growth and protein degradation during early development in chicks of fast and slow growing strains. AB - 1. Growth of breast and leg muscles and excretion of N tau methyl histidine in layer (slow growing) and broiler (fast growing) chicks were measured at five time intervals between 2 and 33 days of age. 2. The results indicate that muscles of the broiler chick grow faster than in layer chicks and that breast muscles of both strains grow faster than leg muscles in the first 2 weeks after hatching. 3. N tau methyl histidine excretion by layer chicks is higher than that by broilers relative to body weight, musculature and relative maturity at all ages examined. 4. The results suggest that faster growth of muscles is accompanied by a lower rate of protein degradation although at ages of less than 2 weeks differences in protein synthesis rates may also contribute to muscle growth. PMID- 2896566 TI - Glomerular filtration rate in wild house mice, Mus musculus, acclimated to water scarcity. AB - 1. A single injection technique for GFR (14C-methoxyinulin clearance) was adapted for use in small mammals and applied to wild house mice (Mus musculus). 2. GFR in controls was 247 +/- 14(SE) microliter/min while that of mice acclimated to water shortage was reduced some 44%. PMID- 2896567 TI - Oxygen consumption of a terrestrial toad (Bufo viridis) and semi-aquatic frog (Rana ridibunda). AB - 1. Oxygen consumption was measured before and after dehydration at different ambient temperatures (Ta) in the terrestrial toad Bufo viridis and the semi aquatic frog Rana ridibunda. 2. The metabolic rates at Tas between 14 and 27 degrees C were almost the same for R. ridibunda and B. viridis. 3. The metabolic rate at higher Tas (between 27 and 36 degrees C) was higher in R. ridibunda than in B. viridis. This situation was found before and after dehydration. 4. A similar situation was found with CO2 production, which was higher at high Tas in R. ridibunda compared with B. viridis. PMID- 2896568 TI - Comparative hormonal profile of two newly developed obese congenic rat strains. AB - 1. The effect of feeding diets containing either 54% sucrose or cooked corn starch for 12 weeks on levels of fasting plasma insulin, corticosterone, growth hormone and glucagon were compared in two newly developed genetically obese rat strains--the normoglycemic LA/N-cp and the diabetic SHR/N-cp. 2. In corpulent rats of either strain, levels of plasma insulin and corticosterone were greater when compared to the lean littermates. Corpulent LA/N-cp rats had lower levels of plasma glucagon and higher levels of plasma growth hormone than did lean LA/N-cp rats. 3. SHR/N-cp rats fed sucrose had greater levels of corticosterone and glucagon than did SHR/N-cp rats fed starch. PMID- 2896570 TI - Comparison of barometric and pneumotachographic measurements of resting ventilation in the little penguin (Eudyptula minor). AB - 1. We compared the use of the barometric method and pneumotachography for measurement of ventilation in the little penguin Eudyptula minor. 2. Simultaneous use of both techniques showed the barometric method to give a reliable estimate of tidal volume. 3. Comparison of birds with and without masks for pneumotachography showed wearing masks to produce a significant increase in ventilation, principally through a raised respiratory frequency. PMID- 2896569 TI - Haematology and metabolism of the blood of the little penguin, Eudyptula minor. AB - 1. We studied the haematology of the little penguin, Eudyptula minor, and measured red cell enzymes, and the rate of O2 and glucose consumption and CO2 and lactate production of whole penguin blood. 2. Little penguins have a very low RBC count (1.66 x 10(12) l-1) and very large red cells (MCV = 229 microns 3), resulting in a normal haemoglobin and haematocrit. 3. Despite the lower body temperature of penguins, the rate of O2 consumption by whole blood is close to that predicted from studies on other birds. PMID- 2896572 TI - Plasma corticosterone in hemorrhaged Japanese quail after microwave irradiation in ovo. AB - 1. Sexually immature male and female Japanese quail were divided within each sex into three treatment groups: hemorrhaged by jugular puncture; immobilized for 2 min, but not hemorrhaged (shams); and neither immobilized nor hemorrhaged (controls). 2. Hemorrhage resulted in increased plasma corticosterone levels in both sexes. Corticosterone levels in shams were higher than in controls. 3. In another experiment, Japanese quail eggs were irradiated during incubation with 2.45 GHz CW microwave radiation. Nonirradiated eggs were incubated under identical conditions without irradiation. After hatching, juvenile males and females were hemorrhaged. 4. After hemorrhage, irradiated males had higher plasma corticosterone levels than nonirradiated males. No effect of irradiation on females was found. 5. The results of these two experiments indicate that male quail respond to blood loss with increased adrenocortical activity and that this response is modified in male quail after irradiation with microwaves during embryogeny. PMID- 2896571 TI - Total and free thyroxine and triiodothyronine in blood serum of mammals. AB - 1. Blood samples were obtained from seven species of mammals: horses, cattle, sheep, goats, pigs, guinea pigs and rats for determination of total and free thyroxine and triiodothyronine. Total thyroxine in the order listed above in ng/ml was: 15, 60, 79, 185, 53, 45 and 79. Free thyroxine in pg/ml was: 5.9, 10.0, 19.2, 32.1, 21.7, 6.7 and 51.3. 2. Total triiodothyronine in pg/ml was: 677, 1290, 979, 3170, 760, 317 and 1747. Free triiodothyronine in pg/ml was: 3.22, 4.40, 2.60, 6.74, 2.74, 2.42 and 10.88. 3. Percent free thyroxine was high in rats and low in guinea pigs, while percent free triiodothyronine was high in guinea pigs and low in goats. 4. Free thyroxine and percent free thyroxine were higher in some groups of horses, particularly stallions, than in other groups. PMID- 2896573 TI - Effects of dietary taurine on tissue taurine and free amino acid levels of the chum salmon, Oncorhynchus keta, reared in freshwater and seawater environments. AB - 1. Young chum salmon were fed on the basal and taurine-supplemented diets for 30 days in freshwater (FW) and for 25 days in seawater (SW). Levels of taurine, major free amino acids (FAA) and non-protein nitrogen (NPN) in various tissues were determined. 2. Tissue taurine levels were higher when fish were fed on the taurine-supplemented diets. All tissues of the SW fish did not contain higher taurine levels than those of the FW. 3. Levels of major FAA in the tissues differed little between fish fed on the basal and taurine-supplemented diets and also between the FW and SW fish. 4. No difference was observed in tissue NPN levels between fish ingesting the basal and taurine-supplemented diets; the levels were slightly higher in the SW fish. PMID- 2896574 TI - Nile crocodiles, Crocodylus niloticus, and estuarine crocodiles, Crocodylus porosus, show similar osmoregulatory responses on exposure to seawater. AB - 1. Nile crocodiles, reared in fresh water and exposed acutely to seawater, suffer marked dehydration and hypernatraemia. Cloacal urine osmolarity and potassium concentration increased markedly but urine sodium remains low. 2. Hypernatraemia is increased when secretion from the lingual salt glands is prevented. 3. C. niloticus appears not to drink seawater. 4. Similarities in osmoregulatory response between estuarine and Nile crocodiles suggest that the lingual salt glands of C. niloticus are functional in salt water, playing an important role in sodium balance. 5. Significant differences in the function of the renal/cloacal complex of Alligator and Crocodylus emphasize further the differences between these two groups of crocodilian and provide support for the postulated marine ancestry of many or all of the Crocodylidae. PMID- 2896575 TI - An axonal spike in an identified fast crab motor neuron has sodium and calcium components. AB - 1. High intensity intracellular stimulation of the FBE axon produced a spike discharge. The spikes divided into two components, each with a different frequency. 2. Ion replacement and blocking specific ion channels revealed that the FBE spike has calcium and sodium components. 3. The pronounced depolarizing wave that follows the FBE spike is not produced by changes in calcium conductance. PMID- 2896576 TI - Hereditary blood coagulation factor-VII deficiency: a comparison of the defect in beagles from several sources. AB - 1. Hereditary blood coagulation factor-VII deficiency has previously been identified in Beagles from a number of sources in Britain and North America. 2. A study is now reported in which the nature of the defect is compared in plasma samples from these sources. 3. When prothrombin times and Russell's Viper venom clotting times were determined on mixtures of samples, no cross-correction of the defective coagulation activity was detected. 4. Antibody neutralization assays of factor-VII related antigen and assays of factor-VII procoagulant activity revealed essentially similar levels in all samples. 5. Thus no significant genetic variants of the defect were identified. PMID- 2896577 TI - Thermoregulatory responses of laying hens under cyclic environmental temperature to intraventricular calcium and sodium. AB - 1. Hens received ICV injections of Ca2+ (1.98 g/100 ml) or Na+ (7.25 g/100 ml) at 28 degrees C and, following acclimation, at 37 or 20 degrees C, respectively. 2. At 28 degrees C (thermoneutrality), rectal temperature rose (P less than 0.05) following Na+ and fell (P less than 0.05) following Ca2+, similar to mammals and broiler chickens. 3. At 37 degrees C, Ca2+-induced hypothermia did not occur; nor did the Na+-associated hyperthermia at 20 degrees C. 4. Acclimation to a high or low temperature may produce an endogenous shift in CSF ion levels that make additional ion administration ineffective in affecting body temperature. PMID- 2896578 TI - Circadian studies of plasma cortisol, thyroid hormone, protein, glucose and ion concentration, liver glycogen concentration and liver and spleen weight in rainbow trout, Salmo gairdneri Richardson. AB - 1. Although there are many reports in the literature of circadian rhythms in plasma hormone and metabolite levels, the data are highly variable between research groups. The present study attempts to re-examine whether circadian rhythm in plasma cortisol, thyroid hormone, ions, glucose and protein levels and liver glycogen levels are evident in rainbow trout, Salmo gairdneri, and determine whether there is a significant correlation between any of the measured variables. 2. Significant fluctuations throughout the day were found in all measured variables; although these fluctuations appear to be a normal component in the homeostatic function of rainbow trout, their timing was neither consistent nor predictable. 3. "Circadian-like" patterns were observed in levels of plasma cortisol, glucose, Mg2+ and K+ concentrations and liver glycogen concentration. 4. Seasonal variations in these circadian-like rhythms were found in liver glycogen and plasma cortisol, Mg2+ and K+ concentrations. 5. Plasma cortisol and glucose concentrations were affected by time of feeding. 6. There were significant correlations between plasma thyroid hormone and plasma protein levels, but no other significant correlation between any of the measured variables was found. PMID- 2896579 TI - Contact allergy to metipranolol. PMID- 2896580 TI - Sea anemone dermatitis. PMID- 2896581 TI - A multicentred phase III comparative study of two hormonal contraceptive preparations given once-a-month by intramuscular injection: I. Contraceptive efficacy and side effects. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation. AB - Two once-a-month injectable contraceptive formulations, HRP112 (depot medroxyprogesterone acetate, 25mg and estradiol cypionate, 5 mg) and HRP102 (norethisterone enantate, 50 mg and estradiol valerate, 5 mg) were compared in two groups of women with regard to effectiveness, reported complaints and reasons for discontinuation. A total of 2328 women were recruited into a seventeen centre, randomized clinical trial. Follow-up was for a period of one year and resulted in a total of 10,969 women-months of experience of HRP112 and 10,608 women-months of experience with HRP102. The study showed little difference in efficacy and side-effects between the two formulations. Two pregnancies occurred in women receiving HRP102, giving a cumulative life-table pregnancy rate at 12 months of 0.18 per 100 woman-years. None occurred in the group receiving HRP112. There was no difference in the overall continuation rates between the two groups at one year, being 64.5% in the HRP112 group and 63.2% in the HRP102 group. The rates for all medical and non-medical reasons given for discontinuation were comparable between the two treatment groups. Discontinuations for bleeding irregularities were low, being 6.3% and 7.5% for HRP112 and HRP102 respectively, as well as for 'amenorrhea', the respective figures being 2.1% and 1.6%. There were, however, marked centre-to-centre differences. Both products were shown to be highly effective contraceptive preparations, which gave rise to few discontinuations due to menstrual cycle disturbances when compared with progestogen-only injectable contraceptives. As such it is expected that they will have an important role in family planning programmes in many countries throughout the world. PMID- 2896582 TI - [Body marking in black Africa]. PMID- 2896583 TI - Inhibition of somatostatin on glucose-induced release of gastric inhibitory polypeptide in rats. AB - The effect of somatostatin on glucoseinduced secretion of insulin and gastric inhibitory polypeptide (GIP) in rats was examined. Anesthetized male rats were catheterized via the right carotid artery before gastric infusion of 2 ml of 40% glucose through a syringe pump over 3 min. Ten micrograms somatostatin dissolved in 0.5 ml saline was injected intraperitoneally 10 min before oral glucose administration. Rats receiving 0.5 ml saline were used as controls. Blood samples were collected at -10, 0, 10, 20, 30, 45, 60, and 90 min after glucose infusion. Concentrations of GIP and insulin in rat plasma samples were measured by radioimmunoassay. The level of plasma glucose was determined by YSI glucose analyzer. The results revealed that the rise of plasma insulin and GIP after the glucose load was abolished by a preinjection of somatostatin. It is concluded that somatostatin at 10 micrograms inhibits the effects of oral glucose in stimulating the secretion of GIP from the gut, and insulin from the pancreas in normal fasted rats. PMID- 2896584 TI - Changes in hepatic and serum gamma-glutamyltransferase activities following chronic ethanol intake in rats. AB - The effect of chronic ethanol consumption on serum and liver gamma glutamyltransferase (GGT) activities was studied in male Wistar rats. Animals were fed for 1-9 weeks a liquid diet containing 36% of total energy as ethanol or isocaloric carbohydrates. Compared to control diet, chronic ethanol significantly and progressively increased serum activity from 3 weeks of treatment. Liver GGT activity was also enhanced although changes were not parallel to those found in serum. Chronic ethanol intake led to an enhancement of liver glutathione concentration with a 45% increase at 3 weeks of treatment and a decrease thereafter. It is suggested that the increased hepatic GGT activity is not the only determinant of the enhanced serum levels of the enzyme and that it is not related to the modifications of liver glutathione content induced by ethanol consumption. PMID- 2896585 TI - Detection of blood benzodiazepines in injured people. Relationship with alcoholism. AB - In 2021 accident victims (household, work and road accidents) the qualitative test for benzodiazepines in the serum by the EMIT method was positive in 9.6% of cases, including 3.2% of subjects who also had a blood alcohol level greater than 0.10 milligram. Benzodiazepines were detected with a particularly high frequency in household accidents and road accidents and rarely in work accidents. These results raise the problem of the role of benzodiazepines as a possible risk factor for accidents, particularly road accidents. PMID- 2896586 TI - Pharmacy-based screening program for tardive dyskinesia. AB - An ongoing screening program using pharmacists to detect tardive dyskinesia (TD) was developed, and a pharmacy-based prevalence survey of TD in chronic hospitalized psychiatric patients was undertaken to determine the extent of abnormal involuntary movements. The results show that older patients and women in particular are at higher risk for developing abnormal movements. Higher doses of neuroleptics were used in non-TD patients, indicating a possible masking effect caused by these drugs. By using a standardized rating method such as the Abnormal Involuntary Movement Scale, pharmacists can and should be utilized in the surveillance of TD. PMID- 2896587 TI - The molecular basis for metameric pattern in the Drosophila embryo. AB - The metameric organization of the Drosophila embryo is generated in the first 5 h after fertilization. An initially rather simple pattern provides the foundation for subsequent development and diversification of the segmented part of the body. Many of the genes that control the formation of this pattern have been identified and at least twenty have been cloned. By combining the techniques of genetics, molecular biology and experimental embryology, it is becoming possible to unravel the role played by each of these genes. The repeating segment pattern is defined by the persistent expression of engrailed and of other genes of the 'segment polarity' class. The establishment of this pattern is directed by a transient molecular prepattern that is generated in the blastoderm by the activity of the 'pair-rule' genes. Maternal determinants at the poles of the egg coordinate this prepattern and define the anteroposterior sequence of pattern elements. The primary effect of these determinants is not known, but genes required for their production have been identified and the product of one of these, bicoid is known to be localized at the anterior of the egg. One early consequence of their activity is to define domains along the A-P axis within which a series of 'cardinal' genes are transcribed. The activity of the cardinal genes is required both to coordinate the process of segmentation and to define the early domains of homeotic gene expression. Further interactions between the homeotic genes and other classes of segmentation genes refine the initial establishment of segment identities. PMID- 2896588 TI - Evidence for an association between U1 RNA and interspersed repeat single-copy RNAs in the cytoplasm of sea urchin eggs. AB - Psoralen crosslinking of RNA-RNA intermolecular duplexes in sea urchin egg extracts reveals that some maternal poly(A)+ RNA molecules are complexed with U1 RNA, a cofactor in somatic nuclear pre-mRNA splicing. Reaction of egg extracts with a monoclonal antibody specific for U1 snRNP selects, in addition to U1, RNAs that contain repeated sequences interspersed with single-copy elements. Antibody selection experiments with nucleate and anucleate egg halves demonstrate that most of the U1 RNA-interspersed RNA complexes are cytoplasmic, as is the egg's store of total U1 snRNP. These results raise the possibility that maternal interspersed RNAs include unprocessed pre-messenger RNA molecules in arrested complexes with splicing cofactors. PMID- 2896590 TI - Targeting of phosphomannosyl-deficient arylsulfatase A to lysosomes of I-cell fibroblasts. AB - Fibroblasts from I-cell disease, a genetically-determined lysosomal storage disease, are shown to contain large amounts of phase-dense lysosomes. These lysosomes accumulated acridine orange and were specifically labeled with antibodies to arylsulfatase A. In normal skin fibroblasts the number of arylsulfatase-containing lysosomes was considerably lower. By immunocytochemistry, metabolic labeling and enzyme assay, the arylsulfatase A in I-cell fibroblasts was shown to be synthesized, stored and secreted at a level that was several-fold higher than that present in heterozygous I-cell or normal fibroblasts. Arylsulfatase A in I-cell fibroblasts differed from arylsulfatase in normal fibroblasts by the absence of endoglycosidase H-sensitive phosphorylated oligosaccharides. These findings indicate that arylsulfatase A in I-cells is targeted to lysosomes by a mechanism that does not appear to involve the phosphorylated mannose marker. PMID- 2896589 TI - Localization of the putative precursor of Alzheimer's disease-specific amyloid at nuclear envelopes of adult human muscle. AB - Cloning and sequence analysis revealed the putative amyloid A4 precursor (pre-A4) of Alzheimer's disease to have characteristics of a membrane-spanning glycoprotein. In addition to brain, pre-A4 mRNA was found in adult human muscle and other tissues. We demonstrate by in situ hybridization that pre-A4 mRNA is present in adult human muscle, in cultured human myoblasts and myotubes. Immunofluorescence with antipeptide antibodies shows the putative pre-A4 protein to be expressed in adult human muscle and associated with some but not all nuclear envelopes. Despite high levels of a single 3.5-kb pre-A4 mRNA species in cultured myoblasts and myotubes, the presence of putative pre-A4 protein could not be detected by immunofluorescence. This suggests that putative pre-A4 protein is stabilized and therefore functioning in the innervated muscle tissue but not in developing, i.e. non-innervated cultured muscle cells. The selective localization of the protein on distinct nuclear envelopes could reflect an interaction with motor endplates. PMID- 2896591 TI - Transient IgA and IgM deficiencies are frequent in children with ulcerative colitis. AB - Serum immunoglobulin levels in 22 children with ulcerative colitis were followed for 2 years after diagnosis of the disease. A statistically significant depression of IgA, IgM, and IgG was noticed; depression of IgA and IgM was most frequent. The depression of immunoglobulin levels was transient and was most prominent during the first year of treatment. All patients in the study received sulphasalazine. Disease activity or steroid medication had no influence on immunoglobulin levels. The development of immunoglobulin deficiencies was not connected with any HLA antigen; we found decreased frequency of antigen B7 in the whole group. PMID- 2896592 TI - Carrier prediction of cystic fibrosis in 36 families by means of restriction fragment length polymorphism. AB - Transmission of cystic fibrosis (CF) was studied in 36 families with at least one affected and one unaffected child. DNA was prepared from peripheral leukocytes and submitted to restriction fragment length polymorphism (RFLP) analysis with two CF probes (pj3.11 and met). Twenty families were shown to be informative so that accurate predictions could be made of the status of the offspring. Sixteen were only partially informative. The allele frequency was similar to that originally reported except for one Msp I site detected with the pj3.11 probe, for which we found a significantly higher heterozygote frequency, making it more informative than expected in our population sample. Pedigree analysis demonstrated no obligate recombinant between CF and the polymorphic markers. PMID- 2896593 TI - Decreased peripheral beta-adrenergic reactivity in asthmatics treated with oral beta 2-agonists. AB - Peripheral beta-adrenoceptor reactivity, measured as the dermal erythematous reaction to iontophoretically administered isoprenaline was studied in 41 asthmatics, 13 patients with allergic rhinoconjunctivitis and 21 healthy control subjects. The response of intact superficial dermal blood vessels to isoprenaline, which has previously been demonstrated to be beta 2-adrenoceptor mediated, was reduced in asthmatics treated with high dose, oral, slow-release beta 2-agonists compared to healthy controls. The response in asthmatics not treated with oral beta 2-agonists and in patients with allergic rhinoconjunctivitis did not differ from controls. Thus, the peripheral beta 2 adrenergic reactivity of intact human superficial blood vessels is affected by oral, slow-release beta 2-agonists. PMID- 2896594 TI - Differential effects of timolol and metoprolol on platelet function at rest and during exercise. AB - Ten male patients suffering from stable angina pectoris were studied at rest and immediately after exercise during treatment either with timolol (a non-selective beta-blocker) or with metoprolol (a beta 1-selective blocker). Timolol induced a significant increase in platelet aggregation and a reduction in platelet cyclic AMP, and it also raised the plasma adrenaline at rest and during exercise as compared to the pre-treatment level. Metoprolol had none of these effects. Prior to medication and during metoprolol treatment, exercise led to an increase in the peripheral platelet count, whereas timolol was associated with a reduction of platelets during physical effort. Neither drug affected platelet thromboxane B2 at rest. During exercise, its level was not affected in the pre-treatment period or during metoprolol treatment but it was sharply increased by timolol therapy. PMID- 2896595 TI - Temporal responses of cutaneous blood flow and plasma catecholamine concentrations to histamine H1- or H2-receptor stimulation in man. AB - We have studied the effect of histamine and H1- or H2-receptor antagonists on cutaneous blood flow and catecholamine release in man. Histamine was infused alone or in combination with mepyramine, an H1-antagonist or cimetidine, an H2 antagonist for 2 h. Cutaneous blood flow was measured continuously with a laser Doppler flowmeter, and noradrenaline and adrenaline concentrations were determined in blood samples drawn every 15 min. The infusion of histamine caused an immediate and sustained vasodilatation. The Concomitant infusion of mepyramine prevented the immediate vasodilatation, but had no effect on the sustained response. The Concomitant infusion of cimetidine was without effect on the immediate vasodilatation, but abolished the sustained response. Infusion of the antagonists alone had no effect on cutaneous blood flow. Histamine caused a rapid and sustained increase in plasma noradrenaline, while the increase during concomitant H1-receptor blockade was delayed but achieved the level observed during the histamine infusion. The response to histamine during H2-receptor blockade was small and transient. The rise in plasma adrenaline was not significant. These findings suggest that histamine causes an immediate cutaneous vasodilatation through H1-receptors and a more sustained response through H2 receptors. The vasodilatation is accompanied by an increase in plasma catecholamine concentrations. Despite the continuous infusion of histamine, blood flow decreased during the last hour of histamine infusion, while the plasma noradrenaline concentration was still elevated. PMID- 2896596 TI - Functional evidence that intercellular adhesion molecule-1 (ICAM-1) is a ligand for LFA-1-dependent adhesion in T cell-mediated cytotoxicity. AB - Although intercellular adhesion molecule-1 (ICAM-1) has been implicated as a ligand in some LFA-1-dependent adhesion, its importance to T cell function has not been established. The present studies investigate the importance of ICAM-1 for human cytotoxic T lymphocytes (CTL), both in their formation of antigen independent conjugates (AIC) and in their lysis of targets. Analysis of monoclonal antibody (mAb) inhibition of AIC formation indicate that ICAM-1 mAb 1 blocks (a) AIC formation with some but not all targets; (b) the LFA-1 pathway but not the CD2/LFA-3 pathway of adhesion; (c) by binding to the target cell, not the T cell. In studies of cell-mediated lysis (CML) ICAM-1 mAb inhibited lysis of some targets, such as U-937, that use ICAM-1 predominantly in AIC formation; CML on some other targets is not inhibited by ICAM-1 mAb. These data indicate that ICAM-1 is a ligand for AIC formation, antigen-specific CTL recognition and cytolysis of particular target cells. The data also indicate that ICAM-1 is not used in LFA-1-dependent CTL interactions with all kinds of target cells, suggesting the existence of alternative ligands for LFA-1. PMID- 2896597 TI - Responsiveness of isolated monkey coronary arteries contracted with alpha 1- and alpha 2-adrenoceptor agonists to diltiazem. AB - Diltiazem induced a concentration-dependent relaxation of monkey coronary arterial strips which were partially contracted with clonidine, phenylephrine, norepinephrine, prostaglandin F2 alpha. This relaxation occurred to a similar extent, but was significantly less than that observed in arteries contracted with K+. Contractions mediated via alpha 2-adrenoceptors do not appear to be more susceptible to diltiazem than those caused by activation of alpha 1-adrenoceptors and prostaglandin F2 alpha receptors. PMID- 2896598 TI - Regulation of A8 dopamine neurons by somatostatin. AB - The effects of depletion of somatostatin in the region of the retrorubral field on in vivo tyrosine hydroxylation in the A8 cell group were assessed. Local injections of cysteamine into the central amygdaloid nucleus, source of a somatostatin input to the A8 cell group region, or directly into the retrorubral field resulted in an increase in in vivo tyrosine hydroxylation in the A8 cell group. Levels of somatostatin-like immunoreactivity in the retrorubral field were decreased by approximately 50% by the cysteamine treatment. These data suggest that somatostatin may hold A8 dopamine neurons under tonic inhibition. PMID- 2896599 TI - Effects of cardioselective beta blockade on the peripheral lung in guinea pigs. AB - Impairment of lung function with selective beta-1 blocking drugs has been repeatedly demonstrated in guinea pigs, normal subjects and asthmatic patients. The effects of several beta blockers, propranolol (non-selective), atenolol (beta 1 selective), IPS 339 (beta-2 selective) on histamine-induced bronchoconstriction have been investigated in 30 anaesthetized and mechanically ventilated guinea pigs, measuring changes in conductance and dynamic compliance. Their effects on peripheral lung, where only beta-2 adrenoceptors are present, were more specifically assessed using changes in lung distensibility by means of static pressure-volume curves. Atenolol (1 mg.kg-1), IPS 339 (2 mg.kg-1) and propranolol (2 mg.kg-1) enhanced histamine-induced decrease in lung distensibility, conductance and dynamic compliance. The decrease was of the same order of magnitude for all three parameters. Atenolol (1 mg.kg-1) and propranolol (2 mg.kg 1) decreased lung distensibility to the same extent. By contrast low dose atenolol (0.1 mg.kg-1) did not potentiate histamine-induced bronchoconstriction although this dose did produce a significant cardiac beta blockade. These results demonstrate that 1) beta blockers have a clear effect on the peripheral lung, 2) beta-1 adrenoceptors are not involved in pulmonary effects of cardioselective drugs. They suggest that dose dependent loss of selectivity is the major mechanism behind impairment of lung function following such drugs. PMID- 2896600 TI - A one year double blind follow-up of blood gas tensions and haemodynamics in almitrine bismesylate therapy. AB - Almitrine bismesylate, a chemoreceptor agonist, improves blood gases in chronic obstructive lung disease (COLD). Some authors have observed an increase in pulmonary artery pressure (Ppa) after single doses of almitrine bismesylate (A). This led to the present one year double blind placebo (P) controlled study to assess haemodynamic effects of long-term oral treatment in COLD (1.5 mg/kg/day for one year), together with clinical benefit and blood gas improvement. Twenty moderately severe patients entered the study, fifteen of whom completed it (eight in group (A), seven in group (P]. Blood gas values, minute ventilation (VE), mean pulmonary artery pressure (Ppa) and cardiac output (Qc) were periodically measured. Ppa and Qc remained unchanged in both groups throughout the study. We observed relevant clinical improvement without side effects and no significant increase in VE in group (A). Arterial oxygen tension (PaO2) showed a 1.2 kPa (9 mmHg) mean increase in group (A) and remained unchanged in group (P). These data and those from the literature seem to indicate that almitrine induces a vascular effect, especially after a single dose. However, as long as PaO2 improves simultaneously no long-term haemodynamic consequence is apparent. The discrepancy between immediate and long-term vascular effects of almitrine might be explained by the improvement in gas exchange which could reduce and/or counter-balance the vasoactive response. In conclusion, after one year of therapy almitrine bismesylate results in considerable clinical and blood gas improvements without significant haemodynamic change. PMID- 2896601 TI - Opioid peptides. Synthesis and binding assays of desamino-Tyr1 dermorphin analogues. XII. AB - Eight new dermorphin peptides, X-C6H4-CH2CH2CO-D-Ala-Phe-(L or D)-Yaa-NH2 [X = H, OH; Y = lysine, homoarginine (Har)], were prepared and tested by binding assays. They show negligible affinity for mu-, delta- and K-receptor sites. These findings indicate that the N-terminal ammonium group can not be replaced by the ammonium or guanidinium function located at the side-chain in Lys or Har derivatives. PMID- 2896602 TI - E. coli F1-ATPase: site-directed mutagenesis of the beta-subunit. AB - Residues beta Glu-181 and beta Glu-192 of E. coli F1-ATPase (the DCCD-reactive residues) were mutated to Gln. Purified beta Gln-181 F1 showed 7-fold impairment of 'unisite' Pi formation from ATP and a large decrease in affinity for ATP. Thus the beta-181 carboxyl group in normal F1 significantly contributes to catalytic site properties. Also, positive catalytic site cooperativity was attenuated from 5 X 10(4)- to 548-fold in beta Gln-181 F1. In contrast, purified beta Gln-192 F1 showed only 6-fold reduction in 'multisite' ATPase activity. Residues beta Gly 149 and beta Gly-154 were mutated to Ile singly and in combination. These mutations, affecting residues which are strongly conserved in nucleotide-binding proteins, were chosen to hinder conformational motion in a putative 'flexible loop' in beta-subunit. Impairment of purified F1-ATPase ranged from 5 to 61%, with the double mutant F1 less impaired than either single mutant. F1 preparations containing beta Ile-154 showed 2-fold activation after release from membranes, suggesting association with F0 restrained turnover on F1 in these mutants. PMID- 2896603 TI - Brain natriuretic factor. Augmentation of cellular cyclic GMP, activation of particulate guanylate cyclase and receptor binding. AB - The newly discovered peptide, brain natriuretic factor (BNF), caused a concentration-dependent increase (up to 400-fold) in intracellular cyclic GMP levels in cultured endothelial, smooth muscle and fibroblast cells. The extent of cGMP augmentation was comparable to that produced by atrial natriuretic factor (ANF). The activity of the membrane-bound guanylate cyclase of different rat tissues and cultured cells was markedly stimulated by the peptide and the addition of ATP potentiated the stimulation. As opposed to tissue particulate guanylate cyclase, the enzyme in cell membranes was slightly more sensitive to activation by BNF than to stimulation by ANF. On bovine aortic smooth muscle (BASM) cells, specific high-affinity binding sites (Bmax = 398 fmol/10(6) cells, Kd = 0.52 nM) for BNF were observed for which ANF could compete with apparently equal affinity. These results suggest that activation of the cGMP pathway constitutes a common mechanism of action for both BNF and ANF. PMID- 2896604 TI - Inhibition of N-acetylneuraminate lyase by N-acetyl-4-oxo-D-neuraminic acid. AB - We show that the 4-oxo analogue of N-acetyl-D-neuraminic acid strongly inhibits N acetylneuraminate lyase (NeuAc aldolase, EC 4.1.3.3) from Clostridum perfringens (Ki = 0.025 mM) and Escherichia coli (Ki = 0.15 mM). In each case the inhibition was competitive. N-Acetyl-D-neuraminic acid; N-Acetylneuraminate lyase; N-Acetyl D-neuraminic acid analog; 5-Acetamido-3,5-dideoxy-beta-D-manno-non-2,4-diulosonic acid; 2-Deoxy-2,3-didehydro-N-acetyl-4-oxo-neuraminic acid; Competitive inhibitor. PMID- 2896605 TI - Intramitochondrial factors controlling hepatic fatty acid oxidation at weaning in the rat. AB - Fatty acid oxidation was studied in isolated liver mitochondria of rats during the suckling-weaning transition. The oxidation rate of oleyl-CoA and palmitoylcarnitine was reduced 2.5-fold in rats weaned on a high-carbohydrate diet compared to suckling rats, when acetyl-CoA produced by beta-oxidation was directed towards ketone-body synthesis. Weaning on a high-fat diet minimized this change. Channeling of acetyl-CoA towards citrate synthesis doubled the oxidation rate of both substrates in HC-weaned rats. Thus, in addition to changes in carnitine palmitoyltransferase I activity, the beta-hydroxymethylglutaryl-CoA synthase pathway is also involved in the decreased fatty acid oxidation at weaning. This was confirmed by measurement of beta-hydroxymethylglutaryl-CoA synthase pathway activity. PMID- 2896606 TI - The gamma-subunit of ATP synthase from spinach chloroplasts. Primary structure deduced from the cloned cDNA sequence. AB - cDNA clones encoding the gamma-subunit of chloroplast ATP synthase were isolated from a spinach library using synthetic oligonucleotide probes. The predicted amino acid sequence indicated that the mature chloroplast gamma-subunit consists of 323 amino acid residues and is highly homologous (55% identical residues) with the sequence of the cyanobacterial subunit. The positions of the four cysteine residues were identified. The carboxyl-terminal region of the chloroplast gamma subunit is highly homologous with those of the gamma-subunits from six other sources (bacteria and mitochondria) sequenced thus far. PMID- 2896607 TI - Posttranscriptional regulation of the expression of CAD gene during differentiation of F9 teratocarcinoma cells by induction with retinoic acid and dibutyryl cyclic AMP. AB - We have studied the regulation of expression of the carbamoyl-phosphate synthetase II-aspartate transcarbamylase-dihydroorotase gene in F9 teratocarcinoma cells during their differentiation into parietal endoderm cells by induction with a combination of retinoic acid and dibutyryl cyclic AMP. Steady state levels of CAD mRNA decreased by 7-fold in F9 cells following 120 h of retinoic acid and dibutyryl cyclic AMP induction as compared to levels in uninduced cells. Conversely, no apparent changes were found in the steady-state levels of beta-actin mRNA between induced and uninduced cells. Despite a 7-fold decrease in the steady-state levels of CAD mRNA, its rate of transcription remained the same between induced and uninduced cells, indicating a role for posttranscriptional mechanisms for its down regulation during retinoic acid- and dibutyryl cyclic AMP-induced differentiation of F9 cells. The cellular growth rate of F9 cells as determined by [3H]thymidine uptake and parallel cell counting decreased markedly during their induction with retinoic acid and dibutyryl cyclic AMP. Taken together, it is apparent that the expression of the CAD gene is cell growth-dependent and its regulation in this system is at the posttranscriptional level. PMID- 2896608 TI - Role of water activity on the rates of acetyl phosphate and ATP hydrolysis. AB - The rates of hydrolysis of acetyl phosphate in the presence of 0.1 M NaOH and of ATP in the presence of either 1 M HCl or 1 M NaOH were measured at different temperatures and in the presence of different concentrations of the organic solvents dimethyl sulfoxide or ethylene glycol. Under all conditions tested, there was a progressive increase in the rate constant of hydrolysis of both phosphate compounds as the water activity of the medium was decreased by the addition of organic solvents. At 25 degrees C, substitution of 70% of the water of the medium by dimethyl sulfoxide promoted an increase of two orders of magnitude in the rate constant of acetyl phosphate hydrolysis. In the presence of 80% and 90% dimethyl sulfoxide the rate of acetyl phosphate hydrolysis increased by more than two orders of magnitude and was so fast that it could not be measured with the method used. The effect of organic solvents on the rate of ATP hydrolysis was less pronounced than that observed for acetyl phosphate hydrolysis. At 30 degrees C, substitution of 90% of water by an organic solvent promoted a 4-6-fold increase of the rate of ATP hydrolysis. Acceleration of either acetyl phosphate or ATP hydrolysis rates was promoted by a decrease in both activation energies (Ea) and in entropies of activation delta S. The data obtained are discussed with reference to the mechanism of catalysis of enzymes involved in energy transduction such as the Ca2+-ATPase of sarcoplasmic reticulum and the F1-ATPase of mitochondria. PMID- 2896609 TI - [Organization of tuberculosis control measures at a feldsher-midwife center]. PMID- 2896610 TI - [Changes in the balance of regulatory subpopulations of T-lymphocytes as a function of the phase of the ovulatory cycle]. PMID- 2896611 TI - Characterization of clotting factors from Agkistrodon acutus venom. AB - 1. Four clotting factors, Cf-1(C), Cf-2(C), Cf-1(T) and Cf-2(T) were isolated from Agkistrodon acutus (collected on mainland China and Taiwan) venom by Komori et al. (1987). It was reported that all factors possessed coagulant activity in the conversion of fibrinogen to fibrin, although they showed different chemical properties and antigenicities. 2. Their role in the clot formation system was clarified and compared with that of thrombin. Clotting factors from A. acutus venom released only fibrinopeptide A from the A alpha chain of fibrinogen, while thrombin released fibrinopeptide A and B from the A alpha and B beta chains. 3. Cf-1(C) and Cf-2(T), like thrombin, rapidly activated factor XIII in the presence of calcium ions, whereas Cf-2(C) and Cf-1(T) had little effect on factor XIII. These effects are shown by Cf-1(C) and Cf-2(T) forming a clot that remained insoluble in 8 M urea or 0.44 M monochloroacetic acid, whereas Cf-2(C) and Cf 1(T) formed a soluble clot in these agents. PMID- 2896612 TI - In vitro differentiation of mouse embryonic yolk sac cells. AB - The embryonic yolk sac is the first site in the mammalian embryo in which cells are found that can carry out cell-mediated immune functions, yet the relation of cells of this primitive hematopoietic organ to the development of the mature immune system has not been established. We have initiated a series of experiments to determine the potential of cells of the mouse yolk sac to differentiate in vitro, in order to get an insight into the development of immunocompetence in this primary population of hematopoietic stem cells. The present paper describes the conditions promoting stem-cell differentiation and provides an initial characterization of cell surface phenotypes of the cell lineages established in vitro. Yolk sac cells obtained from 10- to 13-day mouse embryos were maintained in culture for more than 18 months, giving rise to a variety of cell types belonging to the hematopoietic lineages and culminating in the establishment of long-term cell lines. Supernatants of secondary mixed leukocyte cultures were found to be an effective source of growth factors promoting the initial differentiation as well as the maintenance of these cells. Flow-cytometric analysis showed that, in contrast to freshly obtained yolk sac cells, which had no detectable Thy 1 antigen, cells expressing significant levels of Thy 1 were obtained after 1 week or more of culture. Ly1 and Lyt 2 antigens were detected only rarely and the L3T4 (GK 1.5) antigen was never expressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896613 TI - Influence of pancreatic surgery on gastric ulcers and somatostatin-like immunoreactivity in portal and aortic blood, and in the gastrointestinal tissues of the rat. AB - Two weeks after pancreatic duct occlusion (OCC) or pancreatic half-resection (RES) in rats, the development of gastric ulcers was assessed. Somatostatin-like immunoreactivity (SLI) was measured simultaneously in portal and aortic blood as well as in fundic, antral, duodenal and pancreatic tissue specimens. Extracts of antral, duodenal and pancreatic tissue were chromatographed on a Sephadex G25 superfine column (1.6 +/- 90 cm) under strongly dissociating conditions. As compared to sham-operated controls (SHAM) ulcer index in arbitrary units (AU) and ulcer severity were significantly increased in duct-occluded rats (ulcer index: 5.6 +/- 1.9 AU in SHAM, 42.6 +/- 7.9 AU in OCC; severity: 0.47 +/- 0.37 mm in SHAM, 9.76 +/- 2.37 mm in OCC; p less than 0.001 respectively). Aortic SLI was increased in both experimental groups (SHAM: 53.2 +/- 7.4 pg/ml; RES: 110.9 +/- 16.6 pg/ml, p less than 0.01 vs SHAM; OCC: 96.0 +/- 9.0 pg/ml, p less than 0.001 vs SHAM); portal SLI was decreased in duct-occluded rats (SHAM: 88.9 +/- 7.1 pg/ml; OCC: 65.7 +/- 9.9 pg/ml; p less than 0.05). Tissue SLI was raised in the gastric fundus of duct-occluded rats (SHAM: 6.4/1.3-36.1 micrograms/g; OCC: 8.2/5.1-14.9 micrograms/g; p less than 0.05) and in the duodenum of resected animals (SHAM: 0.7/0.2-1.6 micrograms/g; RES: 1.4/0.4-2.3 micrograms/g; p less than 0.05), but decreased in the duct-occluded pancreas (SHAM: 3.7/1.0-8.2 micrograms/g; OCC: 2.1/0.5-5.6 micrograms/g; p less than 0.05). In all three groups, the major part of total SLI in antrum, duodenum and pancreas was identical with somatostatin-14 at gel chromatography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896614 TI - Different cellular distributions of two somatostatins in brain and pancreas of salmonids, and their associations with insulin- and glucagon-secreting cells. AB - Invariant somatostatin-14 (SST-14) and somatostatin-25 (SST-25), isolated from coho salmon pancreas (Plisetskaya et al., 1986a) are likely coded by two distinct somatostatin genes. The present study was undertaken to investigate whether these genes are expressed in the same or in different cell types in the pancreatic islets and in the brain of two salmonids: rainbow trout and coho salmon. Antibodies generated against SST-14, mammalian (m) SST-28(1-14), salmon (s) SST 25, salmon insulin, and salmon glucagon were used as immunocytochemical probes. Two distinct cell types containing SSTs were revealed in the pancreas of both salmonid species: one cell type immunoreactive to both SST-14 and mSST-28(1-14) and the other cell type immunoreactive only to sSST-25. The SST-14/mSST-28(1-14) positive cells were limited to the more central parts of the islets, in apposition to the insulin-positive cells: sSST-25-positive cells were located more peripherally and were associated topographically with the glucagon-positive cells. In contrast to the pancreas, neurons in the neurohypophysis and hypothalamus of the rainbow trout and coho salmon contained only SST-14-like and mSST-28(1-14)-like immunoreactivities, while immunoreactivity to sSST-25 was completely absent. These results suggest that differentiation in the pancreas and brain of salmonid fishes results in cell types in which SST genes are separately expressed. The close topographical association of sSST-25 with glucagon cells, and of SST-14 with insulin cells, in the pancreatic islets implies yet unknown functional regulatory relationships that require detailed study. PMID- 2896615 TI - Rates and patterns of scnDNA and mtDNA divergence within the Drosophila melanogaster subgroup. AB - Levels of DNA divergence among the eight species of the Drosophila melanogaster subgroup and D. takahashii have been determined using the technique of DNA-DNA hybridization. Two types of DNA were used: single-copy nuclear DNA (scnDNA) and mitochondrial DNA (mtDNA). The major findings are: (1) A phylogeny has been derived for the group based on scnDNA which is congruent with chromosomal data, morphology, and behavior. The three homosequential species, simulans, sechellia, and mauritiana, are very closely related; the scnDNA divergence indicate the two island species are a monophyletic group. (2) The rates of change of scnDNA and mtDNA are not greatly different; if anything scnDNA evolves faster than mtDNA. (3) The rates of scnDNA evolution are not closely correlated to chromosomal (inversion) evolution. (4) The Drosophila genome appears to consist of two distinct classes of scnDNA with respect to rate of evolutionary change, a very rapidly evolving fraction and a relatively conservative fraction. (5) The absolute rate of change was estimated to be at least 1.7% nucleotide substitution per one million years. (6) DNA distance estimates based on restriction site variation are correlated with distances based on DNA-DNA hybridization, although the correlation is not very strong. PMID- 2896616 TI - COPD in the ambulatory elderly: management update. AB - Chronic obstructive pulmonary disease (COPD) is made up of at least three entities: asthma, chronic bronchitis, and emphysema. Each has its own unique physiology, pathology, and natural history. These are reviewed, and current therapeutic options are presented, including the first-line therapy of beta 2 agonists, theophylline, and the newer anticholinergic inhalers. The role of steroids, both acute and chronic, the proper use of antibiotics and vaccinations, and the use of home oxygen therapy, pulmonary rehabilitation, and anxiolytics are discussed. PMID- 2896618 TI - [Experimental studies on the infection of Anopheles and Culiseta by Romanomermis yunanensis]. PMID- 2896619 TI - [Histology, cytochemistry and ultrastructure of APUD cells in the neonatal rabbit lung]. PMID- 2896617 TI - Assessment and management of agitation in the elderly. AB - The management of agitated behavior in the elderly represents one of the major challenges in geriatric medicine. Inappropriate verbal, vocal, or motor activity often results in problem behavior that burdens caregivers or nursing home staff. A careful differential diagnostic approach to agitated behavior is imperative to avoid misdiagnosis. The misuse of psychoactive drugs often begins with an unclear idea of the underlying pathophysiology. Treatment should be combined with an explicit establishment of therapeutic goals and a precise understanding of the pharmacological profiles of commonly used drugs. PMID- 2896620 TI - Identification of a single nucleotide change in a mutant gene for hypoxanthine guanine phosphoribosyltransferase (HPRT Ann Arbor). AB - HPRT Ann Arbor is a variant of hypoxanthine (guanine) phosphoribosyl-transferase (HPRT: EC 2.4.2.8), which was identified in wo brothers with hyperuricemia and nephrolithiasis. In previous studies, this mutant enzyme was characterized by an increased Km for both substrates, a normal Vmax, a decreased intracellular concentration of enzyme protein, a normal subunit molecular weight and an acidic isoelectric point under native isoelectric focusing conditions. We have cloned a full-length cDNA for HPRT Ann Arbor and determined its complete nucleotide sequence. A single nucleotide change (T----G) at nucleotide position 396 has been identified. This transversion predicts an amino acid substitution from isoleucine (ATT) to methionine (ATG) in codon 132, which is located within the putative 5' phosphoribosyl-1-pyrophosphate (PRPP)-binding site of HPRT. PMID- 2896622 TI - Cystic fibrosis: screening for a DNA deletion by field inversion gel electrophoresis. AB - We analyzed DNA of ten cystic fibrosis (CF) patients representing DNA of 19 different CF chromosomes and screened for deletions by means of field inversion gel electrophoresis (FIGE). No differences were detected after digestion of the DNA samples with the restriction enzymes Not I and Sfi I and hybridization with the probes MetH, MetD, J3.11, and 7C22. Thus the percentage of deletions occurring within the CF region and detectable with FIGE is less than 15.2% (95% confidence interval, N = 19). PMID- 2896621 TI - Mitochondrial DNA polymorphism in mitochondrial myopathy. AB - In order to test the hypothesis that mitochondrial myopathy may be caused by mutation of the mitochondrial (mt) genome, restriction fragment length polymorphism in leucocyte mt DNA has been studied in 38 patients with mitochondrial myopathy, 44 of their unaffected matrilineal relatives, and 35 normal control subjects. Previously unreported mt DNA polymorphisms were identified in both patients and controls. No differences in restriction fragment patterns were observed between affected and unaffected individuals in the same maternal line, and there was no evidence of major deletion of mt DNA in patients. This study provides no positive evidence of mitochondrial inheritance in mitochondrial myopathy, but this has not been excluded. PMID- 2896623 TI - Detection of a new hybrid alpha 2 globin gene among American blacks. AB - We have examined the alpha globin gene complex for 49 individuals with alpha thalassemia-2 (-alpha 3.7). Crossovers resulting in alpha-thalassemia-2 (type I) were observed in all 57 chromosomes with the -alpha 3.7 defect. Except for one alpha-thalassemia-2 chromosome, all were linked to the absence of an Rsa I restriction site located 0.7 kb 5' to the alpha 2-globin gene; this polymorphic site was observed for 10 of 38 non-alpha-thalassemia chromosomes from Black Americans. In four Black families with a heterozygous alpha-thalassemia-2 [-alpha 3.7 (I)], an Apa I restriction site has been identified in the IVS-2 of the alpha 2 gene of the normal chromosome (labeled the alpha *2 gene). The alpha *2 gene of one Black subject was cloned and a segment located 5' to the Cap site as well as the IVS-2, exon 3, and a 3' segment were sequenced. The data show that the alpha *2 gene is an alpha 2 gene except for a segment between nucleotides (nts) 580-81 and nt 509 (Cap site = nt 1), and perhaps as far upstream as nt -634, which has an alpha 1 sequence. This alpha *2 hybrid gene probably originated through a double crossover; the structural identity of its IVS-2 with that of the alpha 1 gene adequately explains the presence of the Apa I restriction site. PMID- 2896624 TI - Cystic fibrosis typing with DNA probes: experience of a screening laboratory. AB - A sample of 125 individuals from 37 British cystic fibrosis (CF) families with at least one living affected child were typed with probes for restriction fragment length polymorphisms (RFLPs) known to be linked to the CF gene. These probes were MetD, MetH, pJ3.11 and 7C22. Using this combination of probes, 30 out of the 37 families were sufficiently informative to enable prenatal diagnosis of the disease. Linkage analysis has also proved to be useful in excluding CF in two cases where diagnosis of the disease was equivocal in the sibling of an affected child. PMID- 2896625 TI - The Stickler syndrome: evidence for close linkage to the structural gene for type II collagen. AB - The Stickler syndrome is an autosomal dominant hereditary disorder of connective tissue with pleiotropic features including premature osteoarthropathy, mild spondyloepiphyseal dysplasia, vitreoretinal degeneration, and the Pierre-Robin sequence. Genetic linkage studies in two families with the Stickler syndrome have been performed using restriction fragment length polymorphisms associated with the structural gene for type II collagen, COL2A1. No recombinants between the Stickler phenotype and COL2A1 were observed. The total LOD score for linkage of the Stickler syndrome and COL2A1 at a recombination fraction (theta) of zero is 3.59. These findings suggest that, at least in some families, the mutation causing Stickler syndrome affects the structural locus for type II collagen. PMID- 2896626 TI - Tyrosine aminotransferase and chymotrypsinogen B are linked to haptoglobin on human chromosome 16q: comparison of genetic and physical distances. AB - The loci for haptoglobin (HP) and tyrosine aminotransferase (TAT) are known to reside at 16q22. Chymotrypsinogen B (CTRB), which is syntenic with TAT and HP on mouse chromosome 8, has also been assigned to human chromosome 16 but has not been mapped regionally. A linkage analysis was carried out in 13 informative families using RFLPs for these three markers. For CTRB, two TaqI RFLPs with a polymorphism information content of 0.60 derived from haplotype frequencies are described. The most likely order of loci, deduced from triple informative crosses, and their map distances, obtained by pair-wise linkage analysis, are HP 7 cM-TAT-9 cM-CTRB. By pulsed-field gel electrophoresis, a physical map covering more than 2000 kb was constructed. A maximum physical distance of about 700 kb was obtained for HP and TAT, which contrasts with the genetic distance of 7 cM (approximate confidence limits 2-18 cM). CTRB is at least 800 kb away from these two markers. PMID- 2896627 TI - Long-range genomic map of the Duchenne muscular dystrophy (DMD) gene: isolation and use of J66 (DXS268), a distal intragenic marker. AB - By cloning the endpoints of a DMD-associated deletion, we have "jumped" 1100 kb from pERT87-1 (DSX164) to a new locus designated J66 (DXS268), mapping distally within the Duchenne muscular dystrophy (DMD) gene. Both J66 and JBir are mapped by field-inversion gel electrophoresis and detect abnormal SfiI fragments in DMD patients and distal DMD-associated X; autosome translocations. Our long-range map extends the physical map of the DMD gene from 800 to 2000 kb (2 Mb) and increases the mapped portion of Xp21 to approximately 8 Mb. The position of the glycerol kinase gene and the adrenal hypoplasia locus are further confined to the region between J66 and the nearest distal probe L1-4. This region spans at least 1.5 Mb. The multiallelic J66 polymorphism has immediate application in the diagnosis of DMD and generally appears to be distal to DMD mutations. PMID- 2896628 TI - Linkage analysis in von Recklinghausen neurofibromatosis (NF1) with DNA markers for chromosome 17. AB - The mutant gene causing von Recklinghausen neurofibromatosis (NF1) was recently shown to map to chromosome 17. We have used additional markers for chromosome 17 to narrow further the location of the gene defect. A preliminary multipoint linkage analysis suggests that the NF1 gene is located on the long arm of chroomsome 17, flanked by D17Z1 and NGFR. Linkage analysis with the human oncogene homolog erbA1, which maps to this region, suggests that this cancer related gene is not the primary cause of NF1. PMID- 2896630 TI - Chromosome 17 markers and von Recklinghausen neurofibromatosis: a genetic linkage study in a British population. AB - A genetic linkage study of the RFLPs identified by nine DNA probes localized to the pericentromeric region and long arm of chromosome 17 has been undertaken in 16 families with von Recklinghausen neurofibromatosis (NF1). Close linkage has been shown with the markers CRI-L946 (D17S36), CRI-L581 (D17S37), p17H8 (D17Z1), and pA10-41 (D17S71). The ERBA1 and COL1A1 loci may also be closely linked, but the data are limited. The results for HOX2 and NGFR suggest only loose linkage with the NF1 gene, while no linkage was found between NF1 and the growth hormone locus. No suggestion of nonallelic heterogeneity of NF1 was found in this study. PMID- 2896629 TI - Linkage studies with chromosome 17 DNA markers in 45 neurofibromatosis 1 families. AB - A locus for von Recklinghausen neurofibromatosis (NF1) has recently been mapped near the chromosome 17 centromere. We have extended these linkage studies by genotyping 45 NF1 families with three DNA probes known to be linked to the chromosome 17 centromeric region. Of 34 families informative for NF1 and at least one of the three probes, 28 families show no recombinants with the disease gene. These data provide additional support for genetic homogeneity of NF1 and for a primary NF1 locus linked to the chromosome 17 centromere. Among the informative families were 7 families with apparent new NF1 mutations. Our data suggest that these mutations are probably at the chromosome 17 NF1 locus. PMID- 2896631 TI - Linkage analysis of von Recklinghausen neurofibromatosis to DNA markers on chromosome 17. AB - Several recent studies indicate that the von Recklinghausen neurofibromatosis (NF1) gene is located near the centromere of chromosome 17 in some families. However, variable expressivity and a very high mutation rate suggest that defects at several different loci could result in phenotypes categorized as NF1. In order to assess this possibility and to map the NF1 gene more precisely, we have used two polymorphic DNA markers from chromosome 17 to screen several pedigrees for linkage to NF1. We ascertained a large Caucasian pedigree (33 individuals sampled, 17 NF1 affected) as well as eight smaller pedigrees and nuclear families (50 individuals sampled, 30 NF1 affected). Here, we report strong evidence of linkage of NF1 to the centromeric marker D17Z1 (maximum lod = 4.42) and a weaker suggestion of linkage to the ERBA1 oncogene (maximum lod = 0.57), both at a recombination fraction of zero. Since obligate cross-overs with NF1 were not observed for either marker in any of the informative families tested, the possibility of NF1 locus heterogeneity is not supported. PMID- 2896632 TI - Tightly linked markers for the neurofibromatosis type 1 gene. AB - Relationships among genetic markers in the region of the neurofibromatosis type 1 (NF1) gene on chromosome 17 were investigated by linkage studies in a large sample set of affected families and in a panel of 58 normal families. A new marker, pHHH202 (D17S33), was included along with two markers known to be closely linked to NF. The maximum likelihood estimate of the recombination rate between the pHHH202 and NF1 loci was found to be O. Multilocus analysis suggested the following marker order: pA10-41-(p3-6, pHHH202); the NF1 gene fell with equal likelihood between either pA10-41-p3-6 or p3-6-pHHH202. The odds against NF1 being outside this cluster of tightly linked markers were greater than 15:1. PMID- 2896633 TI - Molecular organization and haplotype analysis of centromeric DNA from human chromosome 17: implications for linkage in neurofibromatosis. AB - The alpha satellite DNA subset located at the centromere of human chromosome 17 has been shown to be tightly linked genetically to the gene for von Recklinghausen neurofibromatosis (NF1). The centromeric DNA polymorphisms used for linkage analyses in NF1 are complex and involve a "locus" (D17Z1) that spans over one million base pairs of satellite DNA. To understand more completely the basis for these polymorphisms and how they might be best scored and used in the analysis of NF1, we have examined the molecular composition of the alpha satellite array on individual copies of chromosome 17 by two complementary approaches. First, we have analyzed segregation of chromosome 17 alpha satellite haplotypes in large, three-generation families that provide information on the different types of alpha satellite segregating in a block fashion. Second, we have analyzed directly the extent of variation in different D17Z1 arrays by genomic blotting analysis of haploid copies of chromosome 17 isolated in rodent/human somatic cell hybrids. The data indicate the existence of a wide range of different alpha satellite variants on individual copies of chromosome 17, each haplotype differing in the size, restriction map, and relative proportion of particular polymorphic repeat forms. Despite this complexity, the D17Z1 markers provide a potentially useful and genetically close starting point for the molecular and clinical analysis of NF1. PMID- 2896634 TI - Linkage of NF1 to 12 chromosome 17 markers: a summary of eight concurrent reports. PMID- 2896635 TI - Effects of beta-blockade and exercise on cardiovascular and cognitive functioning. AB - Twenty-four men with mild essential hypertension were assigned randomly to receive propranolol (n = 9), atenolol (n = 7), or a placebo (n = 8). All subjects participated in a 12-week study and provided physiological and behavioral data four times during the study: after a medication-free baseline period (Session 1); after 2 weeks of medication, without exercise (Session 2); after 8 weeks of continued medication while participating in a program of aerobic exercise (Session 3); and after 2 weeks of maintenance exercise without medication (Session 4). Subjects' maximal oxygen uptake increased significantly between Sessions 2 and 3, and the magnitude of this increase did not vary across the drug groups. Subjects' resting heart rates varied as a function of the presence of beta-blocking medication, but there was in addition a reduction attributable to exercise training that did not vary across the drug groups. The decrease in blood pressure associated with beta-blockade (Session 2) was not decreased any further by exercise training (Session 3). Despite an increase in blood pressure following the withdrawal of active medication (Session 4), blood pressure remained significantly lower compared with the Session 1 baseline level. Performance in a reaction-time test of short-term memory functioning improved slightly for all three groups between Sessions 1 and 2 and remained constant thereafter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896636 TI - The effect of levocabastine nasal spray in nasal provocation tests. AB - The effect of levocabastine, a new specific H1 antagonist, has been investigated against a placebo in nasal provocation tests on 42 allergic patients divided into two parallel groups. The results obtained show that it significantly inhibited the nasal reaction to the allergen and seems to have a long-lasting effect in allergic patients. PMID- 2896637 TI - Applications of BOP reagent in solid phase synthesis. Advantages of BOP reagent for difficult couplings exemplified by a synthesis of [Ala 15]-GRF(1-29)-NH2. AB - The BOP reagent [benzotriazol-l-yl-oxy-tris-(dimethylamino)phosphonium hexa fluorophosphate] introduced by Castro et al. [Tetrahedron Lett. (1975) 14, 1219 1222] is ideally suited for solid phase peptide synthesis. The rate of coupling using BOP compared favorably to DCC and other methods of activation including the symmetrical anhydride and DCC/HOBt procedures. BOP couplings using the solid phase procedure proceeded more rapidly and to a greater degree of completion for peptide bond formations that were previously determined to be very slow using the conventional DCC method. Stepwise solid phase peptide synthesis using BOP was successfully utilized for the preparation of the (22-29) and (13-29) fragments of [Ala15]-GRF(1-29)-NH2. Single couplings with 3 equiv. BOP and Boc-amino acids and 5.3 equiv. of diisopropylethylamine in DMF were used for each cycle. The yields of the fragments were superior and the purities comparable using the BOP procedure (single couplings) to those observed using multiple couplings via the DCC coupling method. A total synthesis of [Ala15]-GRF(1-29)-NH2 was also carried out using the BOP procedure (single couplings and 3 equiv. BOP and Boc-amino acids and 5.3 equiv. diisopropylethylamine in DMF for each cycle). Multiple couplings were only required for Boc-Asn-OH due to the proposed formation of Boc aminosuccinimide during activation. The resultant GRF(1-29) analog was comparable to a control prepared with multiple DCC couplings under optimized conditions. In a parallel study, unprotected Boc-(hydroxy)-amino acids were successfully coupled with the BOP reagent. However, the number of coupling cycles after the introduction of unprotected hydroxy-amino acid must be minimal (less than 10). The use of the BOP reagent with unprotected Tyr in solid phase peptide synthesis was also clearly established. PMID- 2896638 TI - Conformation of D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (CTP-NH2), a highly selective mu-opioid antagonist peptide, by 1H and 13C n.m.r. AB - The 1H and 13C n.m.r. spectral parameters of CTP-NH2 [D-Phe-Cys-Tyr-D-Trp-Lys-Thr Pen-Thr-NH2], a potent, highly selective mu-opiate antagonist, were measured in aqueous solution and a possible conformation has been deduced from the spectral data. The data are consistent with a type II' beta-turn for the tetrapeptide sequence -Tyr3-D-Trp4-Lys5-Thr6-. Solvent shielding of the Cys2 amide proton, observed in variable temperature experiments, suggests an orientation of this amide proton toward the gem dimethyls of Pen7 with possible hydrogen bonding to the Thr6 carbonyl oxygen, and a dihedral angle of -110 degrees for the disulfide bond. Partially relaxed Fourier transform 13C relaxation studies confirm a constrained cyclic system, with the C alpha carbons in the "hinge" of the beta turn having the shortest t1 times. Segmental motion was observed for the side chain of Lys5. PMID- 2896639 TI - Proton n.m.r. investigation of conformational influence of penicillamine residues on the disulfide ring system of opioid receptor selective somatostatin derivatives. AB - Three cyclic disulfide analogs related to somatostatin, D-Phe(1)-cyclo(Cys(2) Tyr(3)-D-Trp(4)-Lys(5)-Thr(6)-Xxx(7))-Thr(8)- NH2 (where Xxx = L-Pen 1; L-Cys 3; or D-Pen 4) were examined in DMSO-d6 by one- and two-dimensional proton n.m.r. spectroscopy in order to analyze the conformational influence of the position-7 residue on the 20-membered disulfide ring. From these studies it was concluded that all three analogs maintain a beta II' turn solution conformation for the core tetrapeptide -Tyr(3)-D-Trp(4)-Lys(5)-Thr(6)-. However, the disulfide conformation differs in the analogs, with 1 and 3 having a left-handed and 4 a right-handed disulfide chirality. PMID- 2896640 TI - [Flexion resistance of soldered alloys for ceramics]. PMID- 2896641 TI - L-653,328: an ocular hypotensive agent with modest beta receptor blocking activity. AB - L-653,328 is the acetate ester of L-652,698 ((S)-3-tert-butylamino-1-[4 [2(hydroxy)ethyl]phenoxy]2-propanol). The penetration of L-652,698 into the albino rabbit eye was enhanced when the compound was instilled as its prodrug acetate ester. The instillation (one drop of 50 microliter) of 0.01, 0.05 and 0.1% solutions of L-653,328 significantly decreased in a dose-dependent manner the elevated intraocular pressure (IOP) of alpha-chymotrypsinized rabbits by 3.2, 4.7 and 6.1 mm Hg, respectively. A 0.01% solution of L-652,698 failed to significantly lower IOP, whereas this dose of timolol (3.8 mm Hg) and betaxolol (3.3 mm Hg) was effective. L-652,698 was active at 0.05% and 0.1%. Extraocular beta-adrenoceptor blockade was quantified in ganglion-blocked, conscious rabbits by determining effects on heart rate and blood pressure changes to i.v. isoproterenol (0.5 microgram/kg). Doses of timolol blocking isoproterenol-induced hypotension and tachycardia by 50% were 0.0065% and 0.03%, respectively. The corresponding doses for betaxolol were greater than 3% (43% inhibition) and 0.3%. Heart rate and blood pressure changes to isoproterenol were blocked by 18 and 36%, respectively, after the instillation of a 3% solution of L-653,328. The reduced propensity of L-653,328 for extraocular beta-adrenoceptor blockade stems from the modest affinity of L-652,698, its active moiety, for beta-adrenoceptors. The Ki values of L-652,698 for displacement of 125I-iodocyanopindolol binding to beta 1-(left ventricle) and beta 2-binding sites (iris + ciliary body) in the rabbit were 5.7 microM and 7.3 microM, respectively. In marked contrast, the corresponding values for timolol were 12 nM and 1.8 nM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896642 TI - Controlled study of extrapyramidal reactions in the management of delirious, medically ill patients: intravenous haloperidol versus intravenous haloperidol plus benzodiazepines. AB - In a prospective study, the intensity of extrapyramidal symptoms (EPS) was rated in two groups of delirious, medically ill patients. Fourteen patients received intravenous (IV) haloperidol and benzodiazepines for control of severe agitation and four received IV haloperidol alone. Patients were rated daily by a standardized scale for EPS by raters blind to the dose of haloperidol and benzodiazepines. Patients receiving haloperidol and benzodiazepines had significantly (p less than 0.001) less EPS than patients receiving IV haloperidol alone. In the haloperidol and benzodiazepine group there were only one case of very mild parkinsonian-like EPS and no cases of akathisia or dystonia. No adverse respiratory or cardiac reactions were seen in any patients. The literature on the use of IV haloperidol alone and in combination with benzodiazepines is briefly reviewed and possible explanations of the lower intensity of EPS with IV haloperidol in combination with benzodiazepines are discussed. PMID- 2896643 TI - Enzyme cytochemistry of rat organs after uremia with special reference to proteases. AB - Wistar rat organs and tissues were investigated after acute and chronic uremia using enzyme cytochemical means whereby special attention was paid to plasma membrane and lysosomal proteases. Heart muscle, pancreas, spleen, stomach, duodenum, jejunum, colon and skeletal muscle did not show any clear-cut indications of alterations. After acute uremia activities of dipeptidyl peptidase IV, glutamyl aminopeptidase and microsomal alanyl aminopeptidase were decreased in the extraorbital gland and that of dipeptidyl peptidase IV in the submandibular gland. The thymus showed an increased staining for glutamyl aminopeptidase and lysosomal proteases. An activity increase of dipeptidyl peptidase IV, acid phosphatase and beta-N-acetyl-D-glucosaminidase occurred in bronchial lavage cells among which the alveolar macrophages predominated. In addition, their number was comparatively higher. Non-specific esterase activity was lowered in these cells. Alkaline phosphatase activity was drastically enhanced at the biliary pole of hepatocytes. Following chronic uremia all effects were less pronounced except for the lavage cells which were positive for glutamyl aminopeptidase, microsomal alanyl aminopeptidase and gamma-glutamyl transpeptidase and showed increased staining for lysosomal proteases, glycosidases and nonspecific phosphatases. PMID- 2896644 TI - Heterogenous staining of D-amino acid oxidase in peroxisomes of rat liver and kidney. A light and electron microscopic study. AB - The localization of D-amino acid oxidase (D-AAOX) in rat liver and kidney has been investigated using the cerium technique for electron microscopy and a recent modification of it for light microscopy. In the liver a mosaic pattern with strongly and weakly stained cells together with some completely negative hepatocytes is observed. The staining is stronger and more uniform in periportal than in perivenous regions of the liver lobule. In the kidney the reaction is confined to the proximal tubules of the renal cortex with the rest of the nephron being negative. At the ultrastructural level in both liver and kidney a marked heterogeneity is observed in the intensity of reaction in peroxisomes of some neighbouring cells. Moreover, in some cells heavily and weakly stained peroxisomes are seen side by side. When Pipes buffer is used in the incubation medium the D-AAOX reaction in kidney peroxiosomes is aggregated in the central region of the matrix with weaker staining of the periphery. A similar result is obtained when the enzyme is localized by immunocytochemistry confirming a recent report by Usuda et al. (1986). The heterogeneous staining of peroxisomes for D AAOX suggests that subpopulations of this organelle with specialized functions may exist not only in different tissues and cells but even within the same cell. PMID- 2896645 TI - Catecholaminergic innervation of pyramidal and GABAergic nonpyramidal neurons in the rat hippocampus. Double label immunostaining with antibodies against tyrosine hydroxylase and glutamate decarboxylase. AB - This study describes the catecholaminergic innervation of rat hippocampal neurons at the electron microscopic level by using an antibody against tyrosine hydroxylase (TH) and immunocytochemical techniques. In a first series of experiments, the course and distribution as well as the synaptic contacts of TH immunoreactive fibers were analyzed with the peroxidase-antiperoxidase (PAP) method. Next, peroxidase immunostaining of TH fibers was combined with glutamate decarboxylase (GAD) immunostaining, using avidinated ferritin as a second electrondense marker. Our results demonstrate that TH-immunostained terminals establish asymmetric synaptic contacts with spines of pyramidal neurons, and symmetric synaptic contacts with cell bodies and dendritic shafts of ferritin labeled GAD-immunoreactive nonpyramidal cells. PMID- 2896646 TI - Are Z-Arg-Gly-Phe-Phe-Leu-MNA and Z-Arg-Gly-Phe-Phe-Pro-MNA suitable substrates for the demonstration of cathepsin D activity? AB - The suitability of Z-Arg-Gly-Phe-Phe-Leu-MNA and Z-Arg-Gly-Phe-Phe-Pro-MNA for the assessment of cathepsin D activity was tested in biochemical and histochemical experiments. Substrates were dissolved in dimethylformamide and used at 0.1-0.5 mM in various buffers over a pH range of 3.5-7.4. Homogenates of various rat organs and isolated purified enzymes [cathepsin D from bovine spleen, dipeptidyl peptidase (DPP) IV from porcine kidney and rat lung] were used as enzyme sources. Pepstatin, di-isopropylfluorophosphate (DFP), p chloromercuribenzoate, o-phenanthroline and a series of DPP IV inhibitors were used in inhibitor experiments. At pH 3.5 and 5.0, substrates were used in a two step postcoupling procedure with aminopeptidase M and dipeptidyl peptidase IV as auxiliary enzymes and Fast Blue BB as coupling agent. Results were compared with those obtained with haemoglobin. Above pH 5.0 substrates were used in a one-step postcoupling procedure. Cryostat sections of snap-frozen or cold aldehyde-fixed tissue pieces of various rat organs and biopsies of human jejunal mucosa were used in histochemical experiments. As in biochemical tests a two-step procedure was used in the pH range 3.5-5.0, but Fast Blue B was used in the second step for the simultaneous coupling. Above pH 5.0 a one-step simultaneous azo coupling procedure was used with Fast Blue B as coupling agent. At pH 3.5 the hydrolysis rate of both synthetic substrates was about 100x lower than that of haemoglobin when cathepsin D from bovine spleen was used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896647 TI - Effect of hypercalcemia on parafollicular cells in the rat thyroid gland. AB - Hypercalcemia was induced in rats by the administration of A.T.10. We then determined the levels of total and ionized calcium and calcitonin in the serum, as well as performed ultrastructural observations and histochemical investigations of the calcitonin and neuron-specific enolase immunoreactivities in the stimulated parafollicular cells. The main aim of the study was to apply histochemical procedures to determine the immunoreactions of calcitonin gene related peptide (CGRP), somatostatin and secretory protein-I in stimulated parafollicular cells. Immunoreactions of CGRP and calcitonin decreased strikingly in A.T.10-treated animals, whereas no visible changes were noted in somatostatin immunoreactivity. In the case of secretory protein-I, an insignificant increase of its immunoreactivity was observed in the treated animals. The cytophysiological significance of these results is discussed. PMID- 2896649 TI - Narcolepsy-cataplexy in Israeli Jews is associated exclusively with the HLA DR2 haplotype. A study at the serological and genomic level. AB - Narcolepsy is a very rare disease among Israeli Jews with a frequency of 7/3 X 10(6). An investigation of the association of narcolepsy with the human leukocyte antigen system was conducted in Israeli Jews at the serologic and genomic levels. The human leukocyte antigen class I and class II antigen typing of 7 clinically diagnosed narcoleptics, 3 individuals suffering from sleep disorders other than narcolepsy, and 11 healthy matched controls revealed that all narcoleptic patients (100%) investigated in the present study carried the HLA-DR2 haplotype, whereas patients with other sleep disorders did not. The HLA-B7 and DR2 occurred jointly in 57% (4/7) of the narcoleptic patients, as compared to 2% in randomly selected Israeli healthy controls. Restriction fragment length polymorphism analysis was performed with several restriction enzymes and three cDNA probes for DQ alpha, DQ beta, and DR beta genes on genomic DNAs obtained from narcoleptics and patients with other sleep disorders, matched controls, and 3 homozygous typing cells representing the DR2 subtypes Dw2, Dw12, and DwAZH. The restriction fragment length polymorphism analysis showed that all narcoleptics (7 of 7) shared virtually identical restriction fragment length polymorphisms with one of the homozygous typing cells (GSO), which defines DR2,Dw2. The frequency of the DR2,Dw2 haplotype in the healthy Israeli population is 3.2%. Other non narcoleptic patients did not share these restriction fragment length polymorphisms. These findings indicate that narcolepsy is associated worldwide with the HLA-DR2,Dw2 haplotype. PMID- 2896648 TI - Disturbances in the rabbit cornea after short-term and long-term wear of hydrogel contact lenses. Usefulness of histochemical methods. AB - The influence of soft contact lenses (SCL) with low (37%, L) and high (65%, H) water content on rabbit corneas was investigated. The lenses were worn continuously for 1, 2, 4, 7, 10, 14, 21 or 28 days. The changes in corneal transparency, hydration and enzyme activities were studied. A slight change in corneal transparency due to higher hydration caused by a decreased activity of Na+-K+-dependent adenosine triphosphatase (Na+-K+-ATPase) in the corneal endothelium is followed by a decrease in the activity of gamma-glutamyl transferase (GGT). Slight morphological disturbances appear within 4 days in animals wearing SCL (L). SCL (H) produce similar changes one week later. Subsequently, the corneal epithelium becomes thinner and changes in the size of corneal endothelial cells are obvious. Disturbances of enzyme activities in cells of all corneal layers are present. In the epithelium highly increased activities of acid glycosidases, acid phosphatase, and dipeptidyl peptidase I and II, in keratocytes decreased activities of alkaline phosphatase and GGT, and in the endothelium decreased activity of Na+-K+-ATPase and GGT were found. These changes are more severe after SCL (L). In this case, inflammatory cells displaying high activities of lysosomal hydrolases appear in the anterior part of the stroma during the 3rd and 4th weeks and local degradation of glycosaminoglycans and proteins takes place. In contrast, after SCL (H) a remarkable thinning of the corneas was observed during extended wear, accompanied by decreased stainability of stromal glycosaminoglycans and highly decreased enzyme activities in keratocytes. The histochemical methods proved very useful in the assessment of lesions caused by a continuous wear of SCL. PMID- 2896650 TI - An interactive computer program for the analysis of HLA class II restriction fragment patterns. AB - There is considerable current interest in the application of Southern blotting and hybridization, with locus-specific HLA class II probes, to HLA typing. The work of several laboratories has shown that, under suitable conditions, restriction fragment patterns that correlate with DR and DQ serology and with DP cellular reactivities can be obtained from homozygous cell lines. Although the identification of class II specificities from restriction fragment patterns is relatively straightforward in homozygotes, the increased complexity of the patterns obtained from heterozygotes makes the interpretation considerably more difficult; this difficulty is compounded by even slight variation between and within gels. We have developed an interactive computer program that allows HLA-DR and DQ typing by the visual matching of restriction fragment pattern data with standard data derived from a panel of well-characterized homozygous cell lines. The program also uses a simple algorithm (after Southern) to estimate the fragment sizes in the unknown track. The screen display can be printed out to give a convenient record of the match; a numerical measure is also given of the goodness of fit of the new data. PMID- 2896651 TI - Restriction fragment length polymorphisms and an HLA-DRw52-associated split. AB - The restriction fragment length polymorphism technique, employing seven restriction endonucleases, and a DR-specific repeated element probe were used to study a large panel of homozygous typing cells in order to delineate haplotypic differences within the HLA-DRw52 supertype. Most of the restriction endonucleases revealed the presence of two allelic restriction fragment length polymorphisms correlating with and splitting the HLA-DRw52 supertypic specificity. One designated A, correlated with the HLA-DRw52 typing in HLA-DR5, HLA-DR3, (non-A1, B8), and some HLA-DRw6 haplotypes. The other, designated a, correlated with the HLA-DRw52 typing in HLA-DR5, HLA-DRw8, HLA-DR3 (A1, B8), and the remaining HLA DRw6 haplotypes. The general applicability of these findings was validated in 47 HLA-typed laboratory controls. PMID- 2896653 TI - Dynamics of EEG slow wave activity during physiological sleep and after administration of benzodiazepine hypnotics. AB - The dynamics of EEG slow wave activity during sleep were investigated in two subjects recorded for 14 consecutive nights, and in 14 subjects recorded for one night after placebo administration. In addition, records were obtained after a single bedtime dose of the benzodiazepine hypnotics flurazepam (30 mg), flunitrazepam (2 mg), triazolam (0.5 mg) and midazolam (15 mg). Mean slow wave activity (i.e. spectral power density in the 0.75-4.5 Hz band) invariably declined from the first to the third nonREM sleep episode. Within episodes, slow wave activity showed initially a gradual buildup over a period of offroximately 35 min, and in the end a rapid decline. Both the rise rates and fall rates decreased over the first three nonREM sleep episodes. The benzodiazepines typically attenuated mean slow wave activity within episodes as well as the rise and fall rates. For three compounds, residual effects were demonstrated in the drug-free post-drug night. We conclude that a homeostatically regulated sleep process determines the buildup rate of slow wave activity within nonREM sleep episodes. PMID- 2896654 TI - The obvious, the obscure, the hidden. Three risks. PMID- 2896652 TI - Ventricular cerebrospinal fluid concentrations of putative amino acid transmitters in Parkinson's disease and other disorders. AB - Concentrations of putative neuroactive substances glutamate, aspartate, gamma aminobutyric acid, glycine, proline and ethanolamine were determined in ventricular cerebrospinal fluid collected in patients suffering from Parkinson's disease, pain syndromes or cerebellar tremor. Values are similar to those given in the literature for lumbar cerebrospinal fluid. A decrease in gamma aminobutyric acid in Parkinson patients, as reported in lumbar cerebrospinal fluid, could not be observed. Further evidence for a rostro-caudal gradient for gamma-aminobutyric acid is supplied. New insights into pathophysiological mechanisms in any of the investigated syndromes may not be derived. PMID- 2896655 TI - Time to change the system. PMID- 2896656 TI - Physicians warned about prescription contests. PMID- 2896657 TI - Changing perspectives in substance abuse and the physician's role. PMID- 2896658 TI - Cysticercosis. PMID- 2896659 TI - Hemolytic uremic syndrome. PMID- 2896660 TI - AMA report focuses on issues. Conflict of interest. PMID- 2896661 TI - Mandatory CME. PMID- 2896662 TI - Polyarteritis nodosa and rheumatic heart disease in a dog. AB - A 12-year-old spayed Corgi-type dog developed an acute febrile illness about 2 weeks after excision of a subcutaneous arteriovenous fistula. The dog was moribund after 1 week of illness and was euthanatized. Necropsy disclosed uncommon lesions comparable to those of polyarteritis nodosa and rheumatic heart disease of human beings. The pathogenesis of the arterial and cardiac lesions was not established, but was consistent with that of an immune-mediated mechanism. PMID- 2896663 TI - Clonal origin of gamma-glutamyl transpeptidase-positive hepatic lesions induced by initiation-promotion in ornithine carbamoyltransferase mosaic mice. AB - Since the deficiency of ornithine carbamoyltransferase (OCT) is inherited as an X linked dominant trait in sparse-fur with abnormal skin and hair (Spf-ash) mice, the livers of heterozygous Spf-ash females show mosaicism in regard to OCT. We induced enzyme-altered foci and nodules, presumptive preneoplastic lesions for hepatocellular carcinomas, in the livers of OCT mosaic mice (Spf-ash x C3H F1), and investigated the clonality of the lesions. Simultaneous histochemical staining for OCT and gamma-glutamyl transpeptidase (GGT) demonstrated that all GGT-positive lesions (ranging in size from 3 cells to a few millimeters in diameter) were either positive or negative for OCT, and no mosaic lesions were detectable. The results indicate that individual enzyme-altered hepatocytic lesions are the result of clonal proliferation. PMID- 2896664 TI - The screening of cattle with potential for developing leukemia by using monoclonal antibody against bovine leukemia cells. AB - Tumor cells from cattle with enzootic bovine lymphosarcoma (EBL) have a tumor associated antigen (TAA) which is distinct from bovine leukemia virus (BLV) induced antigens. We were able to sacrifice 8 TAA-positive cattle with no clinical signs of EBL and to examine whether or not they had gross or histological tumors. At necropsy, 4 animals had tumors macroscopically. Three animals had no tumors histologically but had initial lesions showing follicular hyperplasia and had the TAA on affected lymph nodes. The remaining one showed medullary hyperplasia in the spleen but there were no findings of tumors. These results suggest that most BLV-infected cattle which are TAA-positive but have no clinical signs of EBL, do have tumors and have a higher potential for developing EBL in the future when compared to BLV-infected but TAA-negative cattle. PMID- 2896665 TI - Aggressive dyscontrol in patients treated with benzodiazepines. AB - Periodic reports have suggested that benzodiazepines may be associated with a loss of control over aggressive impulses. Manifestations range from irritability to increased verbal hostility to frank assault. After reviewing data from case reports, experimental studies, and incidence reports, the authors attempt to characterize the phenomenon, estimate the incidence of clinically adverse sequelae to be less than 1%, and find consistent predictive indicators lacking. PMID- 2896666 TI - Depressive symptoms and intellectual functioning in anxiety patients treated with clorazepate. AB - The combined data from two 1970s anxiety studies that used clorazepate and placebo as controls were reanalyzed statistically with a focus on intellectual functioning and depressive symptoms. For the 176 patients given either clorazepate or placebo, significant improvement was observed on the mean scores of the intellectual item and the depressive item of the Hamilton Rating Scale for Anxiety; the clorazepate group was significantly more improved than the placebo group. Similar results were observed in patients' self-ratings. The authors conclude that clorazepate is effective in treating depressive symptoms and improving intellectual functioning in patients with generalized anxiety disorder. PMID- 2896668 TI - A study of prescribed H1-antihistamine preparations over a period of 12 months in community pharmacy. AB - A survey on the prescribing pattern of H1-antihistamine preparations was carried out in four socio-economic areas in Liverpool: the City Centre, an Affluent Area, a Poor area and a Council Estate. The purpose of this study was to find out which H1-antihistamines were prescribed from the wide range available; to discover if there was a trend in the use of these agents over a 12-month period and to suggest possible explanations for these findings. The majority of H1 antihistamine preparations were prescribed in the Affluent Area followed by the City Centre, Poor Area and the Council Estate. In all four areas, over 7.0% of all total items dispensed in a year contained H1-antihistamine drugs, and the lowest use (3.7-9.2%) fell in the summer months while the highest use was in January (8.2-14.1% of items containing H1-antihistamine dispensed per month). Thus the general trend in the use of these drugs may not follow the trend of the hay fever season and it is probably true that H1-antihistamines were more frequently prescribed for treatment of other conditions (common cough and cold) than rhinitis alone. The most widely prescribed classes of H1-antihistamines were alkylamines and ethanolamines, followed by the phenothiazines and ethylenediamines while the piperazines were not prescribed. Triprolidine, diphenhydramine, promethazine and brompheniramine were the top four most widely prescribed drugs. PMID- 2896667 TI - Expression of human tyrosine hydroxylase cDNA in invertebrate cells using a baculovirus vector. AB - A human cDNA containing the complete coding sequence for a human tyrosine hydroxylase (EC 1.14.16.2, form 2) was introduced into the genome of Autographa californica nuclear polyhedrosis virus (AcNPV) downstream to the polyhedrin promoter. Infection of Spodoptera frugiperda cells (SF9) with recombinant virus resulted in the expression of human tyrosine hydroxylase in these invertebrate cells. Characterization of tyrosine hydroxylase activity in infected SF9 cells demonstrated both substrate and cofactor kinetics that were characteristic of those previously reported for the native human enzyme. Both 3-iodotyrosine and alpha-methyl-p-tyrosine competitively inhibited the recombinantly produced tyrosine hydroxylase with Ki values of 1.2 and 16 microM, respectively, similar to those previously reported for the rat and human enzymes. Western blot analysis of extracts of SF9 cells infected with the recombinant baculovirus containing human tyrosine hydroxylase cDNA revealed a major immunoreactive band with an apparent Mr of 60 kDa, identical to the size of the immunoreactive protein from rat adrenal and caudate nucleus. The use of the baculovirus expression system to produce abundant quantities of each of the multiple forms of active human tyrosine hydroxylase in eukaryotic cells should facilitate structural analysis and help clarify the physiological significance of each of the isoenzymes. PMID- 2896670 TI - Presidential messages. PMID- 2896671 TI - Forty-nine years of meetings of the American Academy of Dermatology: 1938 to 1987. PMID- 2896669 TI - Evaluation of in vitro methods for testing ceftriaxone against anaerobic bacteria, including quality control guidelines. AB - Tests with 100 anaerobic bacterial isolates demonstrated comparability between ceftriaxone MICs obtained with the reference agar dilution procedure and those obtained with a broth microdilution susceptibility testing procedure. The aerobically incubated thioglycolate disk elution test was also evaluated. Six 30 micrograms ceftriaxone disks in 5 ml of thioglycolate separated strains for which MICs were less than or equal to 32 micrograms/ml from those for which MICs were greater than or equal to 64 micrograms/ml (6% overall discrepancies). Quality control limits for ceftriaxone agar dilution tests were determined to be as follows: Bacteroides fragilis ATCC 25285, 32 to 128 micrograms/ml; and Bacteroides thetaiotaomicron ATCC 29741, 64 to 256 micrograms/ml. PMID- 2896672 TI - Council on Scientific Assembly. PMID- 2896673 TI - The Academy's annual meeting. PMID- 2896674 TI - The history of the American Academy of Dermatology summer session. PMID- 2896675 TI - Genetic polymorphism of a bovine t-complex gene (TCP1) linkage to major histocompatibility genes. AB - Southern blot analysis of genomic cattle DNA was carried out using murine cDNA probes representing the Tcp-1 gene of the t complex. Excellent cross hybridization was obtained, and the probes apparently hybridized to at least two bovine TCP1 genes. Two independent restriction fragment length polymorphisms, each composed of two allelic variants, were detected; the inheritance of the restriction fragment length polymorphisms was confirmed by family data. One of the restriction fragment length polymorphisms, designated TCP1B, was evidently due to a gene duplication and was revealed with any restriction enzyme used. The duplication was found in three different cattle breeds investigated. Family segregation data indicated that TCP1B is linked to major histocompatibility complex genes. The result was consistent with close linkage to the major histocompatibility complex class II DO beta gene, whereas a fairly high recombination frequency was indicated between TCP1B/DO beta and other major histocompatibility complex genes. The result assigns TCP1B to a bovine linkage group previously comprising major histocompatibility complex class I and class II genes and blood group locus M. The similarity between this linkage group and parts of mouse chromosome 17 (t-H-2) and human chromosome 6 (TCP1-HLA) is discussed. PMID- 2896677 TI - Human enteroviral infections. PMID- 2896676 TI - Cellular and subcellular immunolocalization of L-glutamate decarboxylase in rat pancreatic islets. AB - The cellular and subcellular distribution of L-glutamate decarboxylase (GAD), the biosynthetic enzyme for gamma-aminobutyric acid (GABA), was determined immunohistochemically in rat pancreatic islet using light and electron microscopic techniques. The cellular distribution of GAD was determined at the light microscopic level using an elution/re-staining protocol and a computerized digital image processing technique. At this level of resolution, immunofluorescent GAD was observed to be co-localized with immunofluorescent insulin in the islet B-cells and absent in both the A-cells, which contained glucagon, and the D-cells, which contained somatostatin. Subcellular localization of GAD was determined using an electron microscopic, colloidal gold post embedding protocol and was compared to insulin immunoreactivity in serial sections of the same B-cell. In the same islet B-cell, GAD immunoreactivity appeared predominantly in the extragranular cytoplasm, whereas insulin immunoreactivity was associated with the secretory granules. Quantitative analysis of GAD immunoreactivity in the B-cell revealed 15.3 +/- 1.8 gold particles/micron2 in the cytoplasm, 1.7 +/- 0.2 gold particles/micron2 in the secretory granules, and 0.4 +/- 0.4 gold particles/micron2 in the mitochondria. The results of this study, localization of the biosynthetic enzyme for GABA to the B-cell cytoplasmic compartment and its absence in the secretory granules which contain insulin, are compatible with the hypothesis that GABA functions as an intracellular mediator of B-cell activity. PMID- 2896678 TI - Effect of different surveillance methods on statistics of postoperative wound infections. AB - In two series of clean orthopaedic operations we studied how the rates of postoperative wound infections (PWIs) were influenced by four different surveillance methods. These methods are described and their results discussed. Patients in one series were treated without any collaboration with the Department of Infectious Diseases, whereas in the other patients were isolated and treated in that Department. A prospective 30-day follow-up revealed rates of postoperative wound infection of 3.8% and 2.7% in the two series, respectively. PMID- 2896679 TI - An outbreak of Haemophilus influenzae type b bacteraemia in an intermediate care hospital for children. AB - An outbreak of Haemophilus influenzae type b bacteraemia in the infant unit of a paediatric intermediate care hospital is described. A high attack rate of 36% (four of 11 patients) was found, which was of concern in a population already compromised by chronic illness. The use of rifampicin for all patients in the unit, and staff coming into contact with them, as well as general infection control measures, brought the outbreak to an abrupt halt. The place of rifampicin prophylaxis for hospital contacts of patients with systemic H. influenzae is discussed. PMID- 2896680 TI - Predictors of intraoperative bacterial contamination and postoperative infection in elective colorectal surgery. AB - This prospective study of 238 patients undergoing colorectal operations attempted to identify the risk factors for intraoperative bacterial contamination and postoperative infection. The degree of contamination was assessed by the recovery of Enterobacteriaceae spp. or Staphylococcus aureus in peritoneal irrigation fluid using dip-slides. Uni- and multivariate analyses comprised 17 parameters. Intraoperative contamination was strongly associated with postoperative infection (P less than 0.001). Abdominal drains were correlated with contamination (P = 0.019), but not with infection. Decompressive colostomy was over-represented in patients with contamination (P less than 0.001) but contributed to infection independent of its association with contamination (P less than 0.05), as did advanced age (P less than 0.05). PMID- 2896681 TI - Sources and outcome for methicillin-resistant Staphylococcus aureus bacteraemia. AB - Eighty-eight episodes of MRSA septicaemia occurring in 82 patients were studied prospectively. In 15 episodes bacteraemia was transient, in 36 non-fatal, in 33 fatal, while in four septicaemia was a major contributory factor in the patient's death. There were more patients aged over 60 years in the septicaemia groups compared to the transient bacteraemia group (P = 0.01), and patients with septicaemia were usually recently postoperative and/or suffering from severe underlying disease. Circulation access sites were the commonest source of the bacteraemic organisms with non-surgical wounds including burns, varicose ulcers and bed sores as the next most common. In four of the 16 burns patients, fatal septicaemia followed surgical debridement of infected burns. In only eight episodes was there no apparent source of bacteraemia. PMID- 2896682 TI - Epidemiological characterization of Klebsiella isolates from patients in a renal department. AB - One-hundred-and-eighteen endemic patient isolates of Klebsiella pneumoniae, collected consecutively from clinical specimens of renal patients over a 3 1/2 year period, were studied using biotypes and antimicrobial sensitivity patterns as epidemiological markers. Minor temporal clusters were demonstrable among the more commonly occurring biotypes and resistance types, and comprised isolates acquired inside and outside the renal department. Among isolates acquired in the department two clusters could be demonstrated, in peritoneal dialysate and respiratory tract specimens. Both extended over the whole observation period and occurred independently of the temporal clusters described above. They may have represented common-source outbreaks, but further elucidation was not possible with the data obtained. PMID- 2896683 TI - Antiseptic resistance in JK and other coryneforms. AB - Resistance to five antiseptics was compared in a group of JK coryneform isolates containing plasmids with resistance in cured derivatives of these isolates and in non-JK coryneforms. No evidence of plasmid-mediated resistance was found, but JK coryneforms were more resistant to some antiseptics, particularly DNA-binding compounds, than non-JK coryneforms. PMID- 2896684 TI - Recurrent peritonitis caused by Serratia marcescens in a diabetic patient receiving continuous ambulatory peritoneal dialysis. AB - A diabetic patient treated by continuous ambulatory peritoneal dialysis for end stage renal failure had recurrent peritonitis caused by Serratia marcescens. Thirty-eight isolates of S. marcescens recovered over a 14-month period from peritoneal-dialysis effluent, catheter tips and catheter-exit sites were biotyped and serotyped. The finding that most (90%) of these isolates belonged to the same biotype and serotype suggested that the patient had relapsing infections with the same strain. Similar isolates were recovered from the peritoneal dialysates of another two patients in the same ward, neither of whom developed Serratia associated peritonitis. PMID- 2896686 TI - Epidemiology of Aeromonas species in a hospital. AB - The occurrence of Aeromonas spp. in a hospital water supply, in patients and in the local community was investigated. In healthy persons outside the hospital the isolation rate was 3.6% and among hospital patients it was 6%. Seven per cent of water samples yielded Aeromonas strains. Isolates were typed by sodium dodecyl sulphate polyacrylamide gel electrophoresis of sulphur-35 methionine labelled proteins of Aeromonas isolates. No relationship between water and human isolates could be established, even when a strain of A. hydrophila producing Vero cell cytotoxin contaminated enteral feeds given to patients in the intensive care unit. PMID- 2896685 TI - Influence of disposable ('Conchapak') and reusable humidifying systems on the incidence of ventilation pneumonia. AB - The contamination of disposable ('Conchapak') and reusable humidifying systems and their influence on the incidence of pneumonia was studied in 116 patients requiring continuous mechanical ventilation therapy. The water reservoirs of 11 (15.9%) of the 69 disposable systems became colonized, but all reusable systems were found to be sterile. In four of the 11 samples, the organisms isolated corresponded with those cultured from tracheal secretions several days before. Ventilator-associated pneumonia occurred in 36 (31.0%) of the patients, but there was no statistically significant difference in the incidence of pneumonia between the patients treated with the disposable or the reusable humidifying systems. Gram-negative bacteria were the predominant organisms isolated from tracheal aspirates of patients who developed ventilator-associated pneumonia. These results suggest that disposable humidifying systems do not influence the rate of ventilator-associated pneumonia in mechanically ventilated patients. PMID- 2896687 TI - A disinfectant delivery system for control of micro-organisms in urine collection bags. AB - We developed a formaldehyde delivery system for urine collection bags and evaluated its effectiveness in suppressing the growth of bacteria in simulated human urine. The system was composed of paraformaldehyde in a polymeric carrier. We determined that inoculation of small numbers of Escherichia coli and Pseudomonas aeruginosa in urinary bags with a continuous flow of synthetic urine (40-80 ml h-1) quickly gives rise to high levels of contamination. This single tablet delivery system, however, proved bacteriostatic or bactericidal for both organisms over the 10-day lifespan. The formaldehyde concentration in the synthetic urine was c. 90 micrograms ml-1 or more during tests. PMID- 2896688 TI - Infection control organization in hospitals in England and Wales, 1986. Report of a survey undertaken by a Hospital Infection Society working party. AB - Questionnaires were distributed to hospitals in order to obtain information regarding arrangements for infection control. Returns were obtained from 180 of 200 (90%) health districts in England and Wales covering 95% of 'acute' and 85% of 'other' hospital beds listed in the Hospitals Year Book. The results demonstrated that some form of infection control organization was present in all districts, 98% had control of infection officers and 92% control of infection committees. The proportion of health districts with an infection control nurse had risen from 64% in 1979 to 89%, and the regional variation seen in 1979 was no longer marked. The major commitment of medical microbiologists to infection control was underlined. PMID- 2896689 TI - Epidemic multi-resistant Escherichia coli infection in south London. PMID- 2896690 TI - Demonstration of an outbreak of Serratia marcescens infections in a medical intensive care unit by esterase electrophoretic typing. PMID- 2896691 TI - 1st International Conference of the Hospital Infection Society. London, August 31 to September 4, 1987. Proceedings. PMID- 2896692 TI - Staphylococcal infection in Malaysian hospitals. AB - Staphylococcal infection is common in Malaysian hospitals. A recent survey of 22 Malaysian hospitals revealed that staphylococci were isolated from almost 40% of positive blood cultures. A more detailed analysis of such cases in our own hospital showed that almost 70% of Staphylococcus aureus and about 16% of coagulase-negative staphylococcal isolates were associated with clinically significant disease. Staphylococcal bacteraemia was seen mainly in neonatal sepsis, skin and soft tissue infections, pneumonia, arthritis, osteomyelitis, endocarditis and postoperative sepsis. Multiply-resistant S. aureus were encountered in all the hospitals surveyed. Resistance rates to penicillin ranged from 40% to almost 100% while methicillin resistance rates of up to 25% were reported from several hospitals. PMID- 2896693 TI - Staphylococcal infections in hospital: the Greek experience. AB - Resistance rates of various species to many antimicrobials are very high in Greece. Mean resistance rates of Staphylococcus aureus isolated in 12 Athens hospitals in the second half of 1986 were 80% for penicillin, 32% for methicillin, 22% for gentamicin, 27% for erythromycin, 17% for lincomycin and 16% for co-trimoxazole. In a prospective study in the General Hospital of Athens from May to July 1987, 40 coagulase-positive staphylococcal strains were isolated from various materials from inpatients. Of these 78% were resistant to penicillin, 50% to methicillin at 37 degrees C, 62% to methicillin at 30 degrees C, 38% to erythromycin, 32% to tobramycin, 15% to clindamycin, 15% to fusidic acid, 9% to amikacin, 5% to netilmicin and 0% to vancomycin. Ten of these strains (seven methicillin-resistant) were responsible for severe infections and three of the affected patients died (two nosocomial pneumonias, one infected burn, all due to methicillin-resistant strains). Another 11 strains (eight methicillin-resistant) were responsible for mild infections. From 41 coagulase-negative staphylococci isolated from inpatients, seven (five methicillin-resistant) were held responsible for mild infections. Of the 20 patients with infections due to methicillin-resistant strains, nine had previously received a beta- lactam antibiotic. Staphylococci are not responsible, however, for a large proportion of infections in our hospital at the moment. High resistance rates in Greece are due to overuse of antibiotics, a phenomenon attributed to a consumer's society behaviour of doctors and patients. PMID- 2896694 TI - Overview of current staphylococcal problems in Poland. PMID- 2896695 TI - Epidemiology of resistance among gram-positive bacteria: with special reference to staphylococcal infections. AB - During the past 27-30 years the antibiotic-resistance patterns of Danish Staphylococcus aureus strains have changed from penicillin-, streptomycin resistance, to multiple-resistance ending up today with resistance to penicillin only. These changes have mainly been due to the introduction of different clones with characteristic phage-patterns and antibiotic-resistance patterns; respectively, the penicillin-, streptomycin-resistant strains of the 52, 52A, 80, 81 complex; multiple-resistant strains of the 83A complex and strains of the 94, 96 complex and of type 95 resistant to penicillin only. At the same time, however, changes in antibiotic-resistance pattern within the 52, 52A, 80, 81 and the 83A complex have taken place, and today strains of these complexes are mainly penicillin-resistant only or fully susceptible. Comparison of hospital-acquired strains with community-acquired strains proves that differences are only seen in periods with many resistant strains; today in Denmark these two groups have identical phage-patterns and antibiotic-resistance patterns. The investigations are based on 486412 strains isolated and phage-typed in 1960-86 and on further examination of 12852 strains isolated from blood. PMID- 2896696 TI - Epidemiology of antibiotic resistance in gram-negative bacteria. PMID- 2896697 TI - Clinical impact of drug resistance. PMID- 2896698 TI - Viral hepatitis in hospitals--a clinical overview. PMID- 2896699 TI - Prevention of airborne fungal infection in immunocompromised patients. PMID- 2896701 TI - Hepatitis delta virus. PMID- 2896700 TI - Non A/non B hepatitis. PMID- 2896702 TI - Hepatitis transmission by blood products. AB - The main causes of hepatitis transmission by blood products are hepatitis B and non A non B hepatitis (NANB). A reduction in hepatitis transmission has been achieved by screening blood donors for hepatitis B surface antigen, but it is not known what the effectiveness of screening donors for raised plasma alanine aminotransferase levels or hepatitis B core antibody will be. Attempts to reduce NANB hepatitis transmission have mainly focussed on heat treatment of factor VIII and IX concentrations, and preliminary data suggests that under certain heating conditions inactivation of the NANBvims occurs. Although albuminoid preparations are known not to transmit hepatitis, three immunoglobulin preparations for intravenous administration (IV IgG) have transmitted hepatitis, suggesting that the inclusion of a terminal virucidal step is essential. PMID- 2896703 TI - Treatment of hepatitis. PMID- 2896704 TI - Nosocomial Legionnaires' disease: a global perspective. AB - Nosocomial Legionnaires' disease is a worldwide problem. The lack of prospective surveys using sensitive diagnostic means, such as culture, has resulted in ignorance about the exact magnitude of the problem except at a handful of individual hospitals. Contaminated hospital hot water systems, cooling towers, and non-sterile tap water used for respiratory therapy may all cause disease. Culture diagnosis is the preferred method of case ascertainment, and provides bacterial isolates which can be used to implicate specific environmental sites using molecular epidemiologic techniques. Environmental culture surveys, done in the absence of known disease, are probably not indicated, but there remains concern that wards housing very high risk patients should be legionella-free. Use of monoclonal antibody typing of environmental isolates of L. pneumophila serogroup 1 may be useful in this regard, as it can possibly detect strains most likely to cause disease. Control of nosocomial disease requires centralized management and consultation by expert engineers, epidemiologists, and microbiologists. PMID- 2896706 TI - Nosocomial Legionnaires' disease--advances in diagnosis and typing. AB - The impact of new methodologies on the routine diagnosis of legionella pneumonia has been limited but the potential for advance is considerable. Antigen detection immunoassays have not yet reached the stage where they are used in routine practice. Monoclonal antibodies have been successfully used for direct fluorescence of bronchial aspirates. Nucleic acid hybridization techniques have yet to find a role in diagnosis. Serology remains the most commonly used method in the diagnosis of Legionnaires' disease. Methods of typing Legionella pneumophila include monoclonal antibodies and isoenzyme, plasmid and nucleic acid analysis. Biotyping methods have not been found to be of value. The use of monoclonal antibodies has permitted the comparison of clinical and environmental isolates and allowed the separation of serogroup 1 into subgroups of differing virulence. The subgroup of serogroup 1 called Pontiac is responsible for the majority of sporadic and epidemic legionella pneumonia in the UK. An internationally accepted panel of monoclonal antibodies is used to define these strains. The extent to which other subgroups of serogroup 1 and other serogroups of L. pneumophila cause disease appear to reflect their environmental prevalence. PMID- 2896705 TI - How to deal with a hospital outbreak of Legionnaires' disease. AB - The outbreak of Legionnaires' disease in Glasgow Royal Infirmary is discussed together with the problems such an outbreak poses to the microbiologist. The importance of early diagnosis is stressed. The outbreak was managed by a team drawn up from various disciplines within the hospital. Frank daily reports to the press, together with regular staff meetings with staff representatives helped to allay public anxiety. The subsequent maintenance and monitoring of the wet cooling tower required for the hospital ventilation system have resulted in considerable additional work for the microbiology department but especially for the hospital engineers. PMID- 2896707 TI - Legionnaires' disease outbreaks--the engineering implications. PMID- 2896708 TI - AIDS: epidemiological lessons from the health-care setting. PMID- 2896709 TI - Nosocomial and other difficult infections in the immunocompromised cardiac transplant patient. PMID- 2896710 TI - Controversies about guidelines to prevent the transmission of human immunodeficiency virus in hospitals in Britain. AB - The widespread screening of donors of blood, organs and semen for HIV antibody has contributed greatly to the prevention of spread of HIV to patients in British hospitals. The chances of patients acquiring HIV from a contaminated blood transfusion are now estimated at less than 1 in 1 million and factor VIII for haemophiliacs, which is also heat treated, is now virtually always free of HIV contamination. However, the wider use of HIV antibody tests to identify infected patients and rationalize the application of additional 'inoculation risk' precautions, so as to protect staff, is controversial. The risks of hospital staff acquiring HIV following occupational exposure, without such a screening programme, are extremely low provided a high standard of hygiene is maintained and inoculation injuries are avoided. When needlestick injuries occur, involving HIV infected patients, the chances of transmission of HIV to hospital staff are less than 1 in 100. Current guidelines in Britain depend on use of additional inoculation precautions for patients belonging to HIV risk groups but in practice most of these 'risk patients' are not infected with HIV. Screening HIV antibody tests, preferably with consent, can help the smooth running of operating theatres in areas where many 'risk patients' require surgery, as extra precautions are not necessary for most of these patients who are HIV negative. All antenatal patients should be screened especially in areas of high prevalence of HIV, as this helps to prevent vertical transmission as well as facilitating the rational use of extra precautions to protect health care workers. PMID- 2896711 TI - The evolution of hospital infection control policies concerning AIDS: the current United States debate. PMID- 2896712 TI - How cost-effective is the present use of antiseptics? AB - There are no studies about cost-effectiveness of hand hygiene in the literature. Instead of doing studies about cost-effectiveness, investigations on how to convince doctors and nurses that hand hygiene is absolutely necessary, should be performed. Disinfection by physical methods is more cost-effective than disinfection by chemicals. PMID- 2896713 TI - Are models useful for testing hand antiseptics? PMID- 2896714 TI - What is in the surgeon's glove? AB - Three aspects of surgical hand hygiene have been studied: the attitude of the surgeon, the microbiology of glove changing during an operation, and the use of antiseptic-coated gloves together with different handwash routines. The survey revealed that the predominant factor in choice of agent for surgical hand hygiene was skin tolerance. The microbiological studies showed that 'closed' glove changing was to be preferred to 'open' changing, and that antiseptic-coated gloves further suppressed the skin flora, even after prolonged operations, compared to standard gloves. PMID- 2896715 TI - Prophylactic antibiotics in traumatic wounds. AB - There is well-documented evidence justifying, perhaps demanding, the obligatory use of early, anticipatory treatment in open fractures and in penetrating abdominal wounds, and equally convincing evidence that they are not indicated in fractures of the base of the skull with CSF leaks, in thermal injuries, or in simple lacerations. As far as penetrating chest wounds, and bites are concerned, the evidence is perhaps as yet inconclusive, but antibiotics are probably not indicated in these situations. PMID- 2896716 TI - Effects of antimicrobial prophylaxis on colonization resistance. AB - The effect of antimicrobial agents on the intestinal microflora of patients undergoing colorectal surgery was examined. Two narrow spectrum agents, clindamycin and aztreonam, disturbed colonization resistance. This was preserved with the broad spectrum compound, imipenem. Ecological effects are difficult to predict and clinical studies of new antibiotics should include investigations of their impact on the normal human intestinal flora. PMID- 2896717 TI - Postoperative pneumonia and urinary-tract infection: epidemiology and prevention. AB - Hospital-acquired pneumonias and urinary-tract infections are important causes of morbidity and mortality in surgical patients, and a great deal of effort has been expended on infection control strategies to prevent their occurrence. Prophylactic antibiotics, used either systemically or topically, are not routinely recommended for the prevention of either of these infections. The beneficial effects of these agents are transient, and they are often in association with the acquisition of colonization or infection with resistant bacteria. New approaches for infection control, not involving antibiotic agents, are being developed to lower the infection rates of both hospital-acquired pneumonias and urinary-tract infections to an irreducible minimum. PMID- 2896719 TI - Equipment-related infection risks. PMID- 2896718 TI - Rapid diagnosis of hospital infection: fungal infections. PMID- 2896721 TI - Herpes virus infections. PMID- 2896720 TI - Methods of reprocessing complex medical equipment. AB - The choice as to which of the two gaseous processes is best suited to individual hospital needs is a difficult one. Very few items are unable to tolerate 73 degrees C (LTSF) and these few can withstand 37 degrees C or 55 degrees C (EO). Unfortunately, LTSF is a 'moist' process and sterilizers have a poor history of providing sterilization without modification, and consequently few are used. Ethylene oxide is more reliable, but environmental hazards are greater and running costs high. Both processes are time-consuming and the use of sporicidal disinfectants such as glutaraldehyde is often the only practical alternative. Before purchasing any gaseous sterilizer it is essential to consider throughput and the availability of alternative processes. It may prove sensible to share facilities or at least offer a regional facility. It is certainly not worthwhile purchasing expensive gas sterilizers for reprocessing inexpensive single-use items or for those that require disinfection only. Low temperature steam is safe, inexpensive and no special environmental provisions are necessary. It is, however, not a sterilization process. Disinfectants, hot water and steam will continue to be the only suitable methods for reprocessing items outside the hospital sterile supply department or disinfection unit. Concern over the decontamination of blood-stained instruments following use on patients with hepatitis B or HIV has led to an upsurge of interest in boilers and inexpensive bench top ovens and autoclaves. Such processes are likely to prove more effective than disinfectants but should heat treatment prove impractical then 2% glutaraldehyde or 70% alcohol may be used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896722 TI - Equipment-related infections--national policies. PMID- 2896723 TI - Recent advances in the treatment of pneumonia in the intensive care unit. AB - The treatment of pneumonia acquired in the intensive care unit (ICU) includes intravenous antibiotics and supportive care. In many cases, the aetiologic agent of infection is not clear and empirical broad-spectrum antibiotic regimens are commonly used. Combinations of beta-lactam and aminoglycoside agents are particularly popular due to the high incidence of Gram-negative bacillary and Staphylococcus aureus pneumonias in the hospital setting. Several new approaches to treatment of pneumonia in the ICU are currently being evaluated including single-agent empirical treatment with broad-spectrum beta-lactam agents; intrabronchial aminoglycoside instillation therapy; oral quinolone agents for treatment of Gram-negative bacillary pneumonia; and passive immune therapy. Conventional and experimental therapy are discussed in this report. PMID- 2896724 TI - Hospital infection into the 1990s. PMID- 2896725 TI - Selective decontamination for prevention of infection in ICU patients. PMID- 2896727 TI - Viral typing. AB - Knowing the type and subtype of viruses has often been an essential preliminary to good infection control. A wide variety of methods have been and are used to differentiate virus variants. Examples are given of how some of these biological, immunological and molecular techniques have been used to investigate the epidemiology of some common virus infections. PMID- 2896726 TI - Conventional typing methods. AB - Clinical microbiologists normally identify important isolates to the level of species and determine their susceptibility to antibiotics. These activities generate a species identification and provide some differentiation below the level of species in the form of a biotype and an antibiogram. Most other typing methods should be reserved for special studies or to investigate possible infection problems or outbreaks. Specialized techniques should usually be done in reference laboratories. These include serotyping, (complete antigenic analysis), bacteriophage susceptibility, and bacteriocin production or susceptibility. PMID- 2896728 TI - Host defence to bacterial infection in the neonate. AB - Host defence to bacterial infection is mainly determined by opsonins, i.e., IgG antibodies and complement, and phagocytic cells, which co-operate to remove bacterial invaders from host tissues. Various studies have clearly documented distinct defects in both arms of host defence in the newborn period. Chemotaxis, i.e., directed migration of polymorphonuclear leukocytes (PMN) is impaired in the neonate. Phagocytosis of bacteria by neonatal PMN is normal, but post-phagocytic events, particularly metabolic activation and bacterial killing are impaired, the latter defect apparently due to diminished generation of reactive oxygen species. Both classical and alternative pathway activity of complement are mildly diminished (50-80% of adult values) in the term newborn, but are more severely decreased in the premature infant (20-40% of adult values in 28 to 36 weeks prematures). Opsonic activity of transplacentally-derived IgG when compared to maternal IgG is strikingly deficient against staphylococci and group B streptococci (GBS), in the latter case depending on the GBS serotype. Since opsonization is a key process in antibacterial defence, it is speculated that these opsonic defects of IgG may be an essential determinant of the neonate's susceptibility to disease due to these bacteria. PMID- 2896729 TI - Maternal screening in prevention of neonatal infections: current status and rationale for group B streptococcal screening. AB - Maternal screening--either selective or universal--is an accepted component of a number of strategies for prevention of congenital and perinatal infections. Using the results of maternal screening at prenatal visits and the presence of perinatal risk factors during labour, neonatal group B streptococcal (GBS) early onset disease can be prevented by selective intrapartum chemoprophylaxis. Possible variations on this strategy may employ semiquantitative tests for GBS colonization at prenatal visits or, possibly, rapid bacterial diagnosis intrapartum. Based on the incidence and economic impact of GBS disease, selective intrapartum chemoprophylaxis appears cost-effective in United States populations, but may not be so in countries with lower incidence rates. PMID- 2896730 TI - Neonatal necrotizing enterocolitis: a neonatal infection? PMID- 2896731 TI - The bacterial flora of neonates in intensive care-monitoring and manipulation. AB - Unlike healthy babies, newborns hospitalized in the neonatal intensive care unit (NICU) are colonized with bacterial flora that reflects their exposure to pathogens in the NICU, not bacterial acquired from mother in the perinatal period. For example, nosocomial Gram-negative bacilli, such as klebsiella, enterobacter, and citrobacter but not Escherichia coli tend to colonize the gastrointestinal tract. Colonization with Gram-negative bacilli generally is a prerequisite for nosocomial infection with these pathogens, but surveillance cultures may not be a cost effective approach to predicting which babies will ultimately become ill. However, screening cultures to detect the emergence of antibiotic-resistant Gram-negative bacilli facilitate containment and guide empiric antibiotic therapy, and surveillance cultures are necessary to detect colonized babies when nosocomial Gram-negative bacilli become epidemic in the NICU. Such cultures are inexpensive and easy to perform if appropriate selective media are used. Surveillance cultures to detect coagulase-negative staphylococci, which numerous investigators claim are increasingly important NICU pathogens, are of little value since colonization is virtually universal in the first week of life. Documentation of colonization with group B streptococci or Staphylococcus aureus also cannot be justified on a routine basis. Screening for methicillin resistant S. aureus, however, may be indicated since early detection of these strains can limit dissemination in the NICU. Research aimed at restoring colonization resistance with elements of normal bacterial flora or preventing colonization by nosocomial pathogens is in its infancy. PMID- 2896732 TI - Difficult streptococci. AB - Streptococci pose difficulties in laboratory and clinical diagnosis and in therapy. They are important pathogens with both potential for high mortality in acute infections and endocarditis, and recurrence and persistence in foreign-body associated infections. Prevention of serious infection and spread of infection pose a number of hospital problems but hospital difficulties may originate in community wide outbreaks which also require investigation and control. Our experience with septicaemia caused by Lancefield Group A streptococci, and with Group D streptococcal bacteraemia in liver transplant recipients are reported and both national and international problems with antibiotic resistant streptococci are reviewed. PMID- 2896733 TI - JK coryneforms: a continuing problem for hospital infection control. AB - Control of nosocomial infection is complicated by emergence of endogenous flora as nosocomial pathogens. The JK group of diphtheroids (coryneforms) exemplify this problem. Infection with these organisms is frequent in certain segments of the hospital population and is associated with procedures as well as drug therapy. A number of factors suggest that cross-infection due to JK coryneforms may become even more prominent in the future. Development of rational control measures will require attention to problems of organism definition and methods used for identifying cases, characterizing the patient at risk, and typing organisms in epidemiologic studies. PMID- 2896734 TI - Infections with gram-negative bacilli in a cardiac surgery intensive care unit: the relative role of enterobacter. AB - A 7-month prospective survey for cefazolin-resistant Gram-negative bacilli in cardiac surgery patients, receiving cefazolin prophylaxis, showed that 58 (67%) of 87 were colonized with enterobacter, 37 (64%) with citrobacter, 33 (57%) with Pseudomonas aeruginosa, and seven (2%) with Serratia marcescens. About 50% of colonization occurred before cefazolin prophylaxis and was present on admission to the intensive care unit. Typing of strains showed that horizontal transmission accounted for at most 14% of carriage. Cefazolin prophylaxis (and high gastric pH) were associated with increased levels of postoperative colonization, most notably for enterobacter. About 25% of colonization with enterobacter, pseudomonas, and serratia was followed by clinical infection. Enterobacter cloacae was the most common pathogen and pneumonia the most common infection. Infections contributed to eight of 11 deaths; four of the eight involved enterobacter. Potential control measures include eliminating endogenous Gram negative flora by gut decontamination or at least stemming the increase in level of colonization that occurred after surgery. PMID- 2896736 TI - Campylobacter jejuni infection as a hospital problem: an overview. PMID- 2896735 TI - Database handling for infection control and hospital epidemiology. AB - In 1977 the Department of Microbiology, University College Hospital, London introduced an integrated data processing system. The system was designed primarily to produce individual reports on specimens processed. Input was via visual display units (VDU's) using nmemonic codes. Additionally data is sorted by the software to provide daily, weekly, monthly and annual listings for epidemiological use. Listings concerning specific problem area can be produced as required. As computing power and data storage systems become cheaper it should be possible to improve upon the quality of epidemiological information available. A continuous surveillance system is envisaged where each day all potential outbreaks are displayed and help with their management is offered. Information on incidence of infections and changing trends (such as anti-microbial resistance patterns) would be instantly available in numerical and graphical form. Modern colour VDU's and new programming techniques would make the system especially easy to use by the untrained operator. PMID- 2896737 TI - Clostridium difficile as a nosocomial pathogen. AB - Patients admitted to a 19-bed floor with intermediate nursing care were studied for the onset of Clostridium difficile-associated diarrhoea during a six-month period (181 calendar days) in 1986-87. All admitted patients were reviewed weekly and followed after discharge from the study unit to other inpatient services. Multiple items in the environment of five patients' rooms were sampled bacteriologically for the presence of C. difficile weekly during the study period. Three of the rooms were selected for study because of a higher prevalence of C. difficile associated diarrhoea in the prior three years and two were selected because no cases had been discovered previously in these rooms ('control rooms'). Nine of 521 patients admitted to this unit developed C. difficile diarrhoea (1.73 cases/100 patients admitted) versus 0.30/100 patients admitted to all other sites in our hospital (24 of 7970 other patients). This represented respectively 3.91 cases per 1000 patient days on this floor versus 0.37 patients/1000 patient days throughout the hospital. Seven of the C. difficile diarrhoea cases were associated with stay in the C. difficile associated rooms, versus two cases in the two 'control rooms'. C. difficile was isolated from the toilet seats, bedpan hopper, night stands or food trays. Of some 1955 cultures taken, only 1.9% overall were positive for C. difficile. PMID- 2896738 TI - The prevention and control of mycobacterial infections in hospitals. AB - Infections resulting from contamination of medical equipment and medications with opportunistic mycobacteria are reviewed and the mode of spread discussed. The prevention of Mycobacterium tuberculosis in patients and staff, by the implementation of occupational health schemes, infection control policies and disinfection policies is also reviewed. The problems relating to immunocompromised patients are also discussed. PMID- 2896740 TI - The role of the infection control doctor. AB - The ideal infection control doctor would be a combination of an infectious disease specialist, microbiologist, epidemiologist, social worker, psychologist, teacher, researcher, antibiotic therapy specialist, policeman, priest, supervisor for housekeeping, architect, partner for the infection control nurse, and who should combine the qualities of Mary Poppins, Sherlock Holmes, Francis von Assisi and Margaret Thatcher. A new role is that of a specialist in environmental pollution by detergents, disinfectants and certain disposables. PMID- 2896739 TI - The future of infection control practitioners in the United States. PMID- 2896741 TI - The role of the infection control nurse. PMID- 2896742 TI - Infection control in developing countries. AB - The level of socio-political and economic development achieved by a country determines the quality and quantity of the health care its citizens receive. These factors also govern the amount of attention given to hospital-acquired infection. The problems of infection control in 'developing' countries include, first, the international problems that arise from clashes of personality and viewpoint among those responsible for it, exacerbated in some places by ethnic or religious traditions. Second are problems imposed by factors that affect the spectrum of infectious disease, and third is a variable deficiency of human and financial resources. In the search for solutions, an analysis suggests that nurses are particularly suited to take the lead in the prevention of infection, so that a special initiative directed towards their education in the rapidly developing science of hospital infection and its control is likely to be the most cost effective and appropriate initial approach. This needs to be accompanied by parallel improvements in the education of medical undergraduates. Anything else should be applied in response to measured need, and then only as money and manpower permit. Careful thought is required to avoid squandering scarce resources by applying inappropriate infection control technology. PMID- 2896743 TI - The emergence of fungi as major hospital pathogens. PMID- 2896745 TI - National surveillance programmes. PMID- 2896744 TI - An international survey of the prevalence of hospital-acquired infection. AB - The prevalence of hospital-acquired infection was measured in 47 hospitals in 14 countries in four continents. The aim was to establish the evidence that hospital infection is a common and serious problem throughout the world. Using a standard protocol, 28,861 patients were observed by local teams of doctors and nurses in their own hospitals. The prevalence rates in individual hospitals varied from 3% to 21% (median 8.4%). The highest rates were seen on intensive care (13.3%), surgical (13.1%) and orthopaedic wards (11.2%). Children under the age of 1 year (infection prevalence 13.5%) and adults over 64 years (prevalence 12.0%) suffered more infection than others. In children the commonest infections were of the lower respiratory tract, of the skin and gastroenteritis. In the elderly, urinary tract infections predominated. The prevalence of postoperative wound infection in individual hospitals ranged from 5.2% to 34.4%, with even greater variation when the wounds were analysed as clean, clean-contaminated and contaminated. The micro organisms isolated from infected patients were similar to previous surveys: Escherichia coli and Staphylococcus aureus each caused a sixth of the infections with positive microbiological results. When examined, 30% of patients were on antimicrobial drugs. Penicillin, ampicillin/amoxycillin and gentamicin were the commonest antibiotics used. PMID- 2896746 TI - The hospital environment: how clean should a hospital be? PMID- 2896747 TI - Segregation, collection and disposal of hospital laundry and waste. PMID- 2896748 TI - Pest control in hospitals. PMID- 2896749 TI - Aerobiology in the operating room--a review. PMID- 2896750 TI - Infection control during neutropenia. AB - The first principle of infection prevention in neutropenic patients is to ensure that every effort is made to prevent impairment of the host's defences or any disturbance of the ecological balance of the patient's microbial flora. The second principle is that potential or established sources of infection should be sought and ideally treated before any immunosuppressive therapy is instituted. The third principle is to define the extent to which a particular patient can be expected to benefit from special measures such as protective isolation, sterile or low-pathogen food, decontamination, granulocyte transfusions, passive or active immunization, or antimicrobial prophylaxis aimed at a specific micro organism such as Pneumocystis carinii or Mycobacterium tuberculosis. A programme for the prevention of infections in neutropenic patients will fail if any of these three principles is ignored. PMID- 2896751 TI - Food hygiene in hospitals. AB - Food hygiene in British hospitals is reviewed in the context of national trends in food poisoning and changes in food legislation. New methods of large scale catering such as the cook-chill system are considered, and the safe operation of such a system in a typical health district is described. The application of current guidelines for the microbiological quality of cook-chill food is evaluated. The need for careful observance of these principles, together with appropriate microbiological surveillance of the process and the product, is demonstrated. PMID- 2896752 TI - Novel approaches to hepatitis B vaccine development. PMID- 2896753 TI - Prevention of varicella by vaccination. PMID- 2896754 TI - Impact of molecular biology on Pseudomonas aeruginosa immunization. AB - Persisting high mortalities from Pseudomonas aeruginosa infection have led to new strategies for treatment. In vitro and animal studies indicate that antibodies against P. aeruginosa antigens increase host defense against this infectious agent. The most effective immunogen is lipopolysaccharide (LPS) antigen; however, LPS vaccines are poorly tolerated. Furthermore, the LPS molecule does not lend itself well to production by genetic engineering. Pseudomonas aeruginosa protein antigens which might be amenable to recombinant DNA production are outer membrane proteins and exotoxin A, modified to decrease toxicity but maintain immunogenicity. Another strategy for immunization with anti-LPS P. aeruginosa antibodies is passive administration of either hyperimmune immunoglobulins (polyclonal) or monoclonal antibodies. Passive immunization offers the dual advantage of rapid protection or treatment and is well tolerated. Several monoclonal antibodies against LPS P. aeruginosa antigens have been described, including both murine and human types. Studies in animal models of infection indicate that P. aeruginosa monoclonal antibodies do protect, thus, the most feasible application of molecular biology to the problem of P. aeruginosa infection appears to be production of immunotype-specific monoclonal antibodies for immune therapy. PMID- 2896755 TI - Hantavirus infection: a new imported viral haemorrhagic fever. PMID- 2896756 TI - [Possible involvement of nucleotide diphosphate kinase in membrane signal transduction]. PMID- 2896757 TI - Failure in generating hemopoietic stem cells is the primary cause of death from cytomegalovirus disease in the immunocompromised host. AB - We have shown in a murine model system for cytomegalovirus (CMV) disease in the immunocompromised host that CMV infection interferes with the earliest detectable step in hemopoiesis, the generation of the stem cell CFU-S-I, and thereby prevents the autoreconstitution of bone marrow after sublethal irradiation. The antihemopoietic effect could not be ascribed to a direct infection of stem cells. The failure in hemopoiesis was prevented by adoptive transfer of antiviral CD8+ T lymphocytes and could be overcome by syngeneic bone marrow transplantation. CD8+ T lymphocytes and bone marrow cells both mediated survival, although only CD8+ T lymphocytes were able to limit virus multiplication in host tissues. We concluded that not the cytopathic effect of virus replication in host tissues, but the failure in hemopoiesis, is the primary cause of death in murine CMV disease. PMID- 2896758 TI - Two rare populations of mouse Thy-1lo bone marrow cells repopulate the thymus. AB - Two-color FACS analysis of mouse bone marrow reveals a rare population, comprising 0.1-0.3% of the total, that expresses low levels of the Thy-1 antigen but does not express any of five surface markers that characterize differentiated hematolymphoid cells. We demonstrate here that this fraction of mouse bone marrow is enormously enriched in cells that can home to the thymus and differentiate into mature T lymphocytes, subsequently migrating to peripheral lymphoid organs. Only a subset of the FACS-isolated fraction (1/90 after intrathymic injection) is capable of responding to the thymic microenvironment with a productive commitment to the T cell lineage. A second fraction of mouse bone marrow, which expresses how levels of Thy-1 but is also positive for at least one of five hematolymphoid lineage-specific markers, also contains cells that home to the thymus and establish colonies of thymocytes. The two fractions each contribute approximately equal amounts of thymic colony-forming units (CFUt) to the bone marrow, and together can account for at least half of the CFUt in whole bone marrow. PMID- 2896759 TI - Use of Chinese hamster ovary cells with altered glycosylation patterns to define the carbohydrate specificity of Entamoeba histolytica adhesion. AB - We compared the adherence of E. histolytica trophozoites with a panel of lectin resistant CHO mutants with altered glycosylation patterns. Our results coupled with data from saccharide inhibition studies indicate that terminal N acetyllactosamine units on Asn-linked complex type oligosaccharides provide the major determinants on the cellular receptor for E. histolytica adhesion. PMID- 2896760 TI - Effect of homoserine on growth of Mycobacterium smegmatis: inhibition of glutamate transport by homoserine. AB - Homoserine strongly inhibited growth of Mycobacterium smegmatis in medium containing glutamate as the sole source of nitrogen but was without effect when asparagine, alanine or glutamine was the sole nitrogen source. It was readily taken up by glutamate-grown cells, reaching an intracellular concentration of over 20 mM after 4 h incubation. The primary site of action of homoserine was deduced to be the non-competitive inhibition of glutamate transport. PMID- 2896761 TI - The use of biochemical markers, serotype and fimbriation in the detection of Escherichia coli clones. AB - Biochemical reactions, O and K serotypes and presence of P-fimbriae were analysed in 116 Escherichia coli strains isolated in blood cultures from patients with bacteraemia and in 99 faecal strains isolated from healthy individuals. By using biochemical typing, the strains could be grouped into six main clusters with similarity index less than 0.8 (Gower, 1971) and altogether 16 subclusters with similarity index 0.82-0.89. The most discriminating tests between the clusters were fermentation of D-tagatose, saccharose, salicin and sorbose. No single biochemical property could differentiate bacteraemic isolates from faecal strains, although strains isolated from blood were significantly more often found in certain subclusters, whereas other subclusters contained mainly control strains. Bacteraemic strains possessed P-fimbriae more often, especially strains isolated from patients with E. coli in the urine concomitantly with bacteraemia. Equally, no single reaction could separate P-fimbriated from non-P-fimbriated strains. D-Tagatose was fermented more often by the P-fimbriated strains; on the other hand, melibiose and lactose fermentation tests were less often positive. Certain O serotypes (O1, O4, O6, O7, O18 and O25) were more common among bacteraemic isolates than controls. K serotypes such as K1, K5 and K52 were also more frequent among blood isolates. We conclude that a combination of biochemical tests, fimbriation and serotyping might be used to identify potentially pathogenic clusters of E. coli. PMID- 2896762 TI - Cognitive sequelae of tardive dyskinesia. AB - Severity and location of tardive dyskinesia (TD) symptoms and diagnosis were related to neurocognitive dysfunction as measured by the Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Memory Scale using schizophrenic and affective patients. Diagnosis, severity, and location of TD symptoms were related to cognitive dysfunction. Total symptom severity correlated significantly negatively with 10 of 14 WAIS scores and with four of seven Wechsler Memory scores in the total group with combined schizophrenic and affective patients. The magnitude of the relationships between TD symptom severity and cognitive deficit was strongly affected by the location of the symptoms and the diagnosis of the patient. In the total group, severity of facial TD symptoms correlated significantly negatively with 11 of 14 WAIS scores and with all eight memory scores. TD symptoms in the extremities correlated significantly negatively with only two WAIS and two memory scores, whereas truncal TD symptoms did not correlate significantly negatively with any WAIS or memory scores. Patients diagnosed as schizophrenic showed significant negative correlations of total TD symptom severity with 12 of 14 WAIS scores and with seven of eight Wechsler Memory Scale scores. Patients diagnosed as having affective disorder showed only one significant correlation between total TD symptom severity and WAIS or memory scores. Length of institutionalization has been found to be related to TD symptoms in schizophrenic but not affective patients. In the present study, institutionalization was negatively correlated with severity of facial TD symptoms but not with severity of TD symptoms of the trunk or extremities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896763 TI - HTLV-I-associated meningitis. AB - A 69-year-old woman with human T-cell lymphotropic virus type I (HTLV-I) positive chronic myelopathy became comatose with acute meningitis. Most of the cells in the cerebrospinal fluid were similar to those found in adult T-cell leukaemia/lymphoma, which suggests that there is a close relationship between HTLV-I and this form of meningitis. PMID- 2896764 TI - Mechanisms of long-term potentiation: EPSP/spike dissociation, intradendritic recordings, and glutamate sensitivity. AB - Synaptic efficacy is modified following a brief train of high-frequency stimulation (HFS) to a cell's afferent fibers (long-term potentiation; LTP). An alteration in the postsynaptic response to endogenous neurotransmitter, as a result of an increase in the number of postsynaptic receptors, has been proposed (Baudry and Lynch, 1980). We tested this hypothesis in the CA1 hippocampus by intracellularly recording the postsynaptic response to localized application of glutamate before and after induction of LTP. When LTP was produced, there was no corresponding change in neuronal sensitivity to glutamate application. These findings are not consistent with the hypothesis that HFS of fibers in CA1 stratum radiatum induces an increase in the number of postsynaptic glutamate receptors in CA1 pyramidal cells. Previous reports concerning LTP have indicated a dissociation between the degree of potentiation in the population EPSP and population spike. Simultaneous recordings of the CA 1 population EPSP and population spike in hippocampal slices confirmed that the degree of potentiation of the population spike was not predicted by the degree of potentiation in the population EPSP. Intradendritic impalements were obtained to more accurately assess changes in the intracellular EPSP following HFS. When the population EPSP was potentiated, there was also a potentiated intradendritic EPSP. When the population spike was potentiated following HFS, however, the intradendritic EPSP was often unchanged; in the same cell, there was an increased probability of action potential discharge to stimulation which was originally (i.e., pre-HFS) subthreshold for spike initiation. These results indicate that the EPSP (intracellular or extracellular) may be potentiated following HFS, but this potentiation is not a prerequisite for, or a correlation of, potentiation in the population spike. Furthermore, these findings suggest that LTP is composed of 2 independent components--a synaptic component and an EPSP-to-spike coupling component. PMID- 2896765 TI - Cardiovascular function is altered by picomole injections of glutamate into rat medulla. AB - Local neural circuitry in the nucleus tractus solitarius (NTS) involved in cardiovascular control was studied by injecting nanoliter volumes of excitatory amino acids into the structure. Experiments were performed on urethane anesthetized, artificially ventilated rats. Multibarrel micropipettes were used for pressure ejection of drugs or a dye for marking ejection sites. Ejected volumes, ranging from 200 pl to 25 nl, were directly monitored for every injection. Injections of as little as 200 fmol of L-glutamate in 200 pl into the medial and lateral NTS region rostral to the obex elicited marked, site-specific decreases in arterial pressure and heart rate. The majority of these responses were eliminated by blockade of parasympathetic and sympathetic neural outflow. At sites caudal to obex, in the commissural region of the NTS, L-glutamate injections produced marked elevations in heart rate and arterial pressure which were sympathetically mediated. Responses to L-glutamate were attenuated by concurrent injection of glutamic acid diethyl ester and DL-2-amino-4 phosphonobutyrate, or lidocaine. These results indicate a heterogeneity in the spatial organization of brain-stem circuitry underlying cardiovascular control that has not been previously described. PMID- 2896766 TI - The intermediolateral cell column of the thoracic spinal cord is comprised of target-specific subnuclei: evidence from retrograde transport studies and immunohistochemistry. AB - In this study we examined the hypothesis that the intermediolateral cell column (IML) of the thoracic spinal cord, the nucleus from which preganglionic sympathetic neurons originate, provides an anatomical substrate through which selective regulation of sympathetic nervous system targets is accomplished. Preganglionic sympathetic neurons of rats were retrogradely labeled by the simultaneous exposure of the cervical sympathetic trunk (CST) and the adrenal medulla to Fluoro-Gold and True blue, contrasting fluorescent dyes. Retrograde labeling from these sites revealed 2 populations of sympathetic preganglionic neurons in IML whose distribution overlapped between segments T1 and T4. In regions where these 2 groups of retrogradely labeled neurons overlapped, sympathoadrenal preganglionic (SAP) neurons occupied the most lateral aspect of the nucleus. It was also determined whether individual retrogradely labeled neurons within these two groups sent axon collaterals to both the CST and adrenal medulla. Diamidino yellow, a fluorescent retrograde tracer dye that labels only nuclei, was substituted for Fluoro-Gold and used in combination with True blue to simultaneously label preganglionic sympathetic neurons projecting to either the CST or adrenal medulla. No double-labeled cell bodies were observed in spinal cords of rats treated in this manner. Thus it appeared that the efferent projections of these 2 cell populations in IML were target-specific. Immunohistochemical analysis of the relationship between nerve fibers in the IML and preganglionic sympathetic neurons was also undertaken in an attempt to classify further these 2 populations of sympathetic preganglionic neurons. Equal proportions of identified CST and SAP neurons appeared to be apposed by varicosities immunoreactive for either somatostatin or serotonin. On the other hand, when the comparison was based on whether oxytocin-immunoreactive varicosities appeared to appose these 2 populations of retrogradely labeled sympathetic neurons, a highly significant difference was revealed. That is, oxytocin-immunoreactive fibers and terminals appeared to avoid SAP neurons. Thus these data support the hypothesis that an anatomical substrate exists in spinal cord IML whereby selective regulation of sympathetic nervous system targets may be mediated. Moreover, the lack of oxytocin-immunoreactive varicosities apposing SAP neurons in IML suggests that if the paraventricular nucleus innervates SAP neurons in IML, it does so via a population of neurons that do not use oxytocin as a neurotransmitter. PMID- 2896767 TI - Effect of 711389-S, a new antiarrhythmic agent, on myocardial energy metabolism in guinea-pigs and rats. AB - The effect of 711389-S, a new antiarrhythmic agent, on myocardial energy metabolism was investigated using anaesthetized guinea-pigs and rats. 711389-S elevated the adenylate energy charge and phosphorylation potential in normal guinea-pig myocardium. Large doses also increased the myocardial lactate content with ECG abnormalities. The close relationship between rate-pressure product and the myocardial energy state under 711389-S treatments showed the suppression of energy consumption due to a decrease of work output. In guinea-pigs with arrhythmic myocardia induced by intravenous infusion of ouabain, 711389-S prevented the loss of high-energy phosphate compounds and the acceleration of anaerobic glycolysis concomitant with the effective antiarrhythmic property. In ischaemic myocardium produced by ligation of the coronary artery in rats, 711389 S suppressed the decreases of creatine phosphate, NAD+ and adenylate energy charge. Moreover, this agent effectively blocked the incidence of ventricular arrhythmias at an early stage following the ligation. In all of these actions, 711389-S was more effective than disopyramide, which is in the same class of antiarrhythmics. 711389-S was concluded to be a favourable antiarrhythmic agent offering beneficial action against arrhythmic and ischaemic metabolic changes in the myocardium. PMID- 2896768 TI - Interaction of the anticonvulsants, denzimol and nafimidone, with liver cytochrome P450 in the rat. AB - The presence of an imidazole moiety in the chemical structure of denzimol and nafimidone suggested that these new anticonvulsants might interfere with cytochrome P450-mediated mixed function monooxygenase activities. We therefore investigated their ability to bind reversibly to rat liver cytochrome P450. Both drugs displayed a type II spectra. The Ks values of binding were 6.66 and 7.00 mM, respectively, for denzimol and nafimidone. In other in-vitro studies the IC50 of the inhibition caused by denzimol and nafimidone was determined on carbamazepine (CBZ) epoxidation and diazepam C3-hydroxylation and N1 dealkylation. The IC50 values for CBZ epoxidation were 4.46 x 10(-7) and 2.95 x 10(-7) M, respectively, in the presence of denzimol and nafimidone. The IC50 values for diazepam C3-hydroxylation were 1.44 x 10(-6) and 1.00 x 10(-6) M, respectively, and those for N1-dealkylation 6.66 x 10(-7) and 5.95 x 10(-7) M. The inhibition of CBZ metabolism was also investigated ex-vivo and in-vivo after single oral doses (15 and/or 60 mg kg-1) of denzimol or nafimidone. Inhibition of CBZ-10,11-epoxidation by the two drugs was time- and dose-dependent. Further studies in-vivo showed that denzimol and nafimidone prolong pentobarbitone sleeping times indicating that both drugs bind to rat liver microsomes and are potent inhibitors in the rat of mixed function monooxygense activities both in vitro and in-vivo. PMID- 2896769 TI - Involvement of prostaglandin E-like material in the purgative action of rhein anthrone, the intraluminal active metabolite of sennosides A and B in mice. AB - Intracaecal administration of rhein anthrone, the intraluminally active metabolite of sennosides A and B, to mice quickly induced severe diarrhoea. Pretreatment with the prostaglandin (PG) biosynthesis inhibitor, indomethacin, and PGE2 antagonist, SC-19220, prevented the onset of diarrhoea induced by rhein anthrone, but the PGE2 antagonist polyphoretin phosphate (PPP) showed only a weak inhibitory effect. Rhein anthrone stimulated the production of PGE-like material only in the colon and its large intestinal propulsive activity was depressed by indomethacin and SC-19220, but not by PPP which suggests that the release of PGE like material has some role in its purgative action. PMID- 2896770 TI - Pharmacological profile of new histamine H2-receptor antagonists related to cimetidine, ranitidine and lamtidine. AB - New compounds structurally related to cimetidine, ranitidine and lamtidine have been prepared and tested for their histamine H2-receptor blocking activity on guinea-pig atria, rat perfused stomach and frog isolated gastric mucosa. These derivatives contain as a polar group, a diaminofurazan moiety, a 3-amino-4 methylfurazan or a 3-amino-4-phenylfurazan moiety. Ranitidine and lamtidine analogues display strong H2-antagonist activity in-vitro (KB on atria 0.037 microM and 0.0039 microM, respectively) and in-vivo on the lumen-perfused stomach of the anaesthetized rat (ID50 0.13 mumol kg-1 and 0.023 mumol kg-1 i.v., respectively). However, lamtidine analogues are ineffective in blocking the histamine-induced increase of H+ output in the frog isolated gastric mucosa. On the basis of the anomalous results in the frog, it is concluded that caution must be exercised in extrapolating information from amphibian to mammalian tissues with regard to the structure and the function of histamine receptors. PMID- 2896771 TI - Retention of soman in rats, guinea-pigs and marmosets: species-dependent effects of the soman simulator, pinacolyl dimethylphosphinate (PDP). AB - Whether the temporary retention of intact soman in the rat and its subsequent delivery from tissues into the circulation of the blood is also demonstrable in guinea-pigs and marmosets has been investigated as was whether the soman simulator PDP (pinacolyl dimethylphosphinate) prevented this retention. Electric eel AChE, intravenously injected 1.5 h after an intravenous soman intoxication into anaesthetized, atropinized and artificially ventilated guinea-pigs (150 micrograms kg-1 soman), marmoset monkeys (100 micrograms kg-1 soman) and rats (330 and 172.5 micrograms kg-1 soman) lost its activity faster than enzyme injected in non-intoxicated animals. Electric eel AChE incubated in the presence of pectoralis or diaphragm muscle isolated from soman-intoxicated rats, guinea pigs and marmosets 0.5 or 1.5 h after the intoxication, was progressively inhibited, indicating that those muscles still delivered soman into the incubation medium. In rats, PDP (6.4 mg kg-1 i.v.) pretreatment was effective in preventing inhibition of intravenously injected electric eel AChE 1.5 h after intoxication with a high dose of soman (330 micrograms kg-1). But after intoxication with a low dose (172.5 micrograms kg-1), PDP pretreatment was ineffective in this action, however, it did lead to less soman delivery from muscle tissue isolated 30 min following the 172.5 micrograms kg-1 soman intoxication, suggesting that there was less soman in the tissue. In PDP (6.4 mg kg-1 i.v.)-pretreated marmosets (100 micrograms kg-1 soman) and guinea-pigs (150 micrograms kg-1 soman), to the contrary, the trend was for the injected AChE to be more inhibited, whereas only slightly less soman was delivered from isolated muscle tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896772 TI - Identification of 15-hydroperoxyabietic acid as a contact allergen in Portuguese colophony. AB - 15-Hydroperoxyabietic acid (15-HPA) has been isolated from Portuguese colophony of the gum rosin type and identified as its methyl ester. The structure of the compound was elucidated using UV, IR, NMR and mass spectrometry. 15-HPA methyl ester was found to be an elicitor when tested in colophony-sensitized guinea pigs. The sensitizing capacity was verified in the same species and 15-HPA methyl ester was considered to be a strong allergen. The eliciting potential was also verified in patients with known allergy to colophony. The Portuguese gum rosin investigated contained approximately 1% of 15-HPA. Based on its allergenicity and the amounts isolated, we conclude that 15-HPA is a main contact allergen in Portuguese gum rosin. PMID- 2896773 TI - Enantiomer resolution of nefopam hydrochloride, a novel analgesic: a study by liquid chromatography and circular dichroism spectroscopy. AB - Nefopam, a potent analgesic, has been completely resolved into enantiomers on a preparative scale by low-pressure liquid chromatography on swollen, microcrystalline triacetylcellulose. The enantiomerically pure hydrochlorides were prepared from the base, and the circular dichroism spectra of the free base and the hydrochloride are reported. PMID- 2896775 TI - The inhibitory effect of liposome-encapsulated indomethacin on inflammation and platelet aggregation. AB - A comparison has been made between liposome-encapsulated and free indomethacin for their anti-inflammatory activities in the carrageenan paw oedema test in rats, and their inhibitory effect on platelet aggregation induced by adenosine 5 diphosphate (ADP) in-vitro. Free indomethacin, 3 mg kg-1, strongly inhibited carrageenan-induced oedema and a similar inhibitory activity was shown by 0.3 mg kg-1 of encapsulated drug. For the inhibition of platelet aggregation, the threshold concentration of free drug was 0.559 mM. At this concentration, at least 5 min incubation was needed to achieve 12.5% and 45 min for 50% inhibition. The inhibition was much stronger with encapsulated drug, and pre-incubation of 28 microM encapsulated drug for 10 min with platelet-rich plasma before addition of ADP completely inhibited platelet aggregation. PMID- 2896776 TI - Evidence for a functional cholinergic deficit in human colonic tissue resected for constipation. AB - There is evidence to suggest an abnormality of the colonic myenteric plexus in severe chronic constipation. The present study investigates whether this abnormality involves functional changes in the cholinergic innervation of human colon. Human taenia coli muscle strips (taenia), previously incubated with [3H]choline to radiolabel neuronal stores of acetylcholine, were subjected to electrical field stimulation (1 Hz or 10 Hz, 1 ms, 480 pulses at 200 mA). The stimulation evoked release of tritiated material, shown previously to accurately represent neural [3H] acetylcholine release, was depressed in tissue from constipated compared with non-constipated patients. Evoked release of tritiated material was reduced by storage of the taenia at 4 degrees C or by increasing the frequency of stimulation, but increased by stimulation during incubation with [3H]choline. The results indicate that reduced activity of cholinergic nerves may occur within the bowel wall of colon removed for severe chronic constipation. PMID- 2896774 TI - Distribution of 7-hydroxymethotrexate in human blood. AB - We have examined the in-vitro distribution of 7-hydroxymethotrexate (7-OH-MTX), a cytotoxic metabolite of methotrexate (MTX), in human blood, and its protein binding in serum. The distribution of 7-OH-MTX (10(-6) M) in fresh samples of whole blood was studied at 37 degrees C and pH 7.51 +/- 0.05 (mean +/- s.d.), and its protein binding was assessed by equilibrium dialysis of serum against Krebs Ringer phosphate buffer at 37 degrees C and pH 7.41 +/- 0.07 (mean +/- s.d.). 7 OH-MTX had a mean cell/plasma concentration ratio of 0.03 (range 0-0.27, n = 18). It was extensively bound in human serum, with a bound fraction of 90.4 +/- 3.3% (mean +/- s.d.) in healthy volunteers (n = 11), and significantly lower, 82.3 +/- 4.0% (mean +/- s.d.), in hypoalbuminaemic surgical patients (n = 7). The binding of 7-OH-MTX was correlated with serum albumin (HSA) concentrations (r = 0.72, P less than 0.0007, n = 18). Blood distribution data support the contention that 7 OH-MTX has a small volume of distribution, and HSA appears to be mainly responsible for the high degree of its protein binding in serum. PMID- 2896777 TI - Myoclonic seizures in the mouse induced by alphaxalone and related steroid anaesthetics. AB - The anaesthetic steroids alphaxalone. 5 beta-alphaxalone and pregnanolone each caused myoclonic jerks in mice in a dose-related manner between 4 and 16 mg kg-1 i.v. There was no loss of righting reflex at these doses. The veterinary product Saffan, which contains alphaxalone and alphadalone, also caused myoclonic jerks at 2 mg kg-1 i.v., and a loss of righting reflex at doses of 4 mg kg-1 and above. These effects appear to be unrelated to the wide spectrum of potencies at the GABAA receptor complex of the three individual steroids as potentiators of muscimol, or as attenuators of picrotoxin. PMID- 2896778 TI - Effects of zinc sulphate on gastric mucosal blood flow and gastric emptying of the rat. AB - Zinc sulphate (50 mg kg-1 p.o.) did not modify basal gastric mucosal blood flow, as measured by [3H]aniline clearance, but inhibited its reduction by noradrenaline (3.5 micrograms kg-1 min-1). Zinc sulphate also influenced gastric emptying of phenol red but its effects depended upon the dose; 30 mg kg-1 caused no variation whereas 80 mg kg-1 induced a significant delay. The nature of both actions is discussed and their implications in the development and prevention of gastric ulceration have been analysed. PMID- 2896779 TI - Eudistomin derivatives, novel phosphodiesterase inhibitors: synthesis and relative activity. AB - The preparations of novel phosphodiesterase inhibitors, 8-acetoxy-5-iodo-6 methoxypyrido[3,4-b]indole, 5,7-dibromo-6-hydroxypyrido[3,4-b]indole, 5,7 dichloro-6-hydroxypyrido[3,4-b]-indole and 8-acetoxy-5-bromo-6-methoxypyrido[3,4 b]indole, are described together with concentrations giving 50% inhibition against cyclic AMP phosphodiesterase, i.e. 3 X 10(-6), 3 X 10(-6), 7 X 10(-6) and 1 X 10(-5) M, respectively. The relative potency of these eudistomin derivatives is discussed in terms of the chemical structures compared with those of other inactive eudistomins and derivatives. PMID- 2896780 TI - Bunitrolol metabolism and its inhibition by cimetidine. AB - A simple fluorometric assay method as well as a sensitive HPLC method for determination of bunitrolol, a beta-adrenoreceptor blocking drug, and its 4 hydroxylated metabolite is described. More than 90% of bunitrolol metabolized was accounted for by the formation of 4-hydroxybunitrolol in rat hepatic microsomes. Bunitrolol 4-hydroxylation required NADPH, and was inhibited by CO, proadifen and metyrapone, indicating that this reaction is mediated by cytochrome P450. This reaction was also inhibited by cimetidine competitively, and the inhibition constant, Ki, was 40 +/- 11.5 microM (mean +/- s.e. n = 3). PMID- 2896781 TI - Effects of minaprine, a novel antidepressant, on prolactin secretion in the rat. AB - The effect of minaprine, a novel psychotropic drug with antidepressant properties, on prolactin secretion has been investigated in the rat. On intraperitoneal administration (10 and 20 mg kg-1) it significantly decreased basal prolactin levels. In contrast, both haloperidol (1 mg kg-1 i.p.) and morphine (20 mg kg-1 i.p.) increased serum prolactin levels and daily treatment with oestradiol (100 micrograms kg-1 s.c.) for 4 days also elevated the levels. Minaprine at a dose of 20 mg kg-1 failed to antagonize the elevation of serum prolactin levels induced by these drugs. The results imply that minaprine may not exert a direct inhibitory action on prolactin secretion at the pituitary gland. PMID- 2896783 TI - Formation and release of [3H]acetylcholine in the rat urinary bladder strip. AB - The relationship between different frequencies of loading stimulation and [3H]acetylcholine (ACh) formation and release from nerve terminals has been investigated in extratrigonal strips of the urinary bladder of the rat. An increase in frequency (0.2, 0.4 and 0.8 Hz) for the 30 min incubations with [3H]choline produced an enhancement of storage of [3H]ACh from 19.5 to 34% of total tritium content in the tissue. Higher frequencies (1.6 and 3.2 Hz) failed to increase storage further on. The [3H]choline content did not vary significantly. Electrical field stimulation at 2 Hz (360 shocks) produced a release of tritium. The evoked outflow was higher when the strip was loaded at 0.8 Hz than at the other frequencies tested. Both [3H]ACh and [3H]choline were measured in the perfusate of strips preloaded at 0.8 Hz. Most of the induced outflow was found to be [3H]ACh, as in previous experiments carried out using 0.2 Hz as a loading frequency. The findings suggest that in the rat urinary bladder strip loading at 0.8 Hz is suitable for increasing the formation and the resulting release of [3H]ACh during electrical stimulation. PMID- 2896782 TI - Effects of AN-132 and quinidine, antiarrhythmic agents, on plasma digoxin concentrations in rats. AB - The effects of AN-132, 3-(diisopropylaminoethyl-amino)-2',6' dimethylpropionanilide.2H 3PO4, on chloroform-induced arrhythmias and plasma digoxin concentrations have been compared with those of quinidine in rats. AN-132 (0.01-3 mg kg-1) administered orally significantly inhibited the incidence of cardiac arrhythmias in a dose-related fashion. A single dose of digoxin (1 mg kg 1) given orally for 7 consecutive days was followed, on day 8, orally by digoxin alone, or together with AN-132 (50, 100 and 200 mg kg-1) or quinidine (25 and 50 mg kg-1). The AUC0-24 and Cmax of plasma digoxin were enhanced significantly by co-administration of quinidine, but not by AN-132. PMID- 2896784 TI - Stereoselectivity of kappa-opiate receptor ligands in inhibiting the binding of [3H][3-MeHis2]thyrotrophin releasing hormone to brain membranes. AB - The effect of (+/-)-, (-)- and (+)-isomers of several ligands for kappa-opiate receptors on the binding of [3H][3-MeHis2]-thyrotrophin releasing hormone ([3H]MeTRH) to rat brain membranes has been determined. [3H]MeTRH bound to rat brain membranes at a single high affinity site with maximal binding capacity (Bmax) of 48 +/- 2 fmol(mg protein)-1, and an apparent dissociation constant, Kd of 4.6 +/- 0.2 nM. At a concentration of 2 nM, the specific binding of [3H]MeTRH was 12.3 +/- 0.6 fmol(mg protein)-1. The isomers of ketocyclazocine, tifluadom (1 methyl-2-(3-thienylcarbonyl) aminomethyl-5-(2-fluorophenyl) H-2,3-dihydro-1,4 benzodiazepine), and alpha-5,9-diethyl-2'-hydroxy-2-(3-furylmethyl)-6,7 benzomorphan [MR 2266 (-), MR 2267 (+)] were used for interaction studies. The ( )-isomer of each of the above drugs was more potent than the (+)-form in inhibiting the binding of [3H]MeTRH to brain membranes, whereas the (+/-)-forms had activity intermediate between (-)- and (+)-forms. The order of activity of kappa-ligands was tifluadom greater than MR 2266 greater than ketocyclazocine. It is concluded that kappa-opiate drugs inhibit the binding of [3H]MeTRH to brain membranes in a stereoselective manner with tifluadom being the most potent drug. PMID- 2896786 TI - Influence of adrenocorticotrophic hormone on the behaviour in the swim test of rats treated chronically with desipramine. AB - Chronic desipramine (DMI) administration induced a dose-dependent reduction in the immobility time of the swim test in rats. A combined treatment of ACTH (50 iu kg-1 s.c.) and DMI (5 or 10 mg kg-1 i.p.) for 7 days potentiated the anti immobility effect of DMI. ACTH 4-10, a fragment peptide with little corticotrophic activity, mimicked ACTH-induced potentiation. No stimulating effect on locomotor activity was observed following seven daily co administrations of ACTH or ACTH 4-10 and DMI (10 mg kg-1). This behavioural evidence indicates that ACTH potentiation involves a central mechanism and demonstrates a functional interaction between ACTH and DMI at the behavioural level. PMID- 2896785 TI - Structure-activity relationship of hylambatin and its fragments as studied in the guinea-pig ileum. AB - Hylambatin (Hyl), a dodecapeptide isolated from the skin of the African frog, Hylambates maculatus, belongs to the family of tachykinin or physalaemin-like peptides. Hylambatin and its 12 fragments were tested in the guinea-pig ileum preparation for contractile activities. All fragments except 3 had contractile activities. The C-terminal fragment as short as the octapeptide sequence was at least as active as the parent molecules. The heptapeptide fragment (Hyl6-12) and the hexapeptide fragment (Hyl7-12) were less active and the C-terminal pentapeptide fragment (Hyl8-12) and the N-terminal hexapeptide fragment (Hyl1-6) were much less active. The N-terminal pentapeptide fragment (Hyl1-5) and the N terminal fragment from which the N-terminal Asp or Asp-Pro residues were removed (Hyl2-6, Hyl3-6), were inactive at doses used. PMID- 2896787 TI - The guinea-pig trachea O-methylating system is more effective in modulating beta 2- than beta 1-adrenoceptor-mediated responses to isoprenaline. AB - Assuming that responses of the guinea-pig trachea to isoprenaline in the presence of atenolol (10 mumol L-1) are exclusively, or at least predominantly, beta 2 adrenoceptor mediated and that responses to isoprenaline in the presence of ICI 118,551 (erythro-DL-1(7-methylindan-4-yloxyl)-3-isopropylaminobut an-2-ol) (1 nmol L-1) are exclusively, or at least predominantly beta 1-adrenoceptor mediated, the influence of inhibition of COMT by U-0521 (dehydroxy-2-methyl propiophenone) (50 mumol L-1) has been compared in both conditions. U-0521 enhanced beta 2-adrenoceptor mediated responses to isoprenaline 3.3-fold, while those mediated by beta 1-adrenoceptors were enhanced only 2.2-fold. It is concluded that in guinea-pig trachea COMT activity is functionally more effective in modulating responses which are mediated by beta 2-adrenoceptors than responses mediated by beta 1-adrenoceptors. PMID- 2896788 TI - The discrimination between human, porcine and bovine insulin with 1H NMR spectroscopy. AB - The 1H- and 1H-1H correlation (COSY) NMR spectra of human, porcine and bovine insulin have been recorded. The 1.1-1.5 ppm regions of these spectra show the methyl signals of the alanine and threonine residues. The number of alanines and threonines differs for the three insulins and thus allows an easy discrimination with NMR. PMID- 2896789 TI - Antidiarrhoeal activity of bisnordihydrotoxiferine isolated from the root bark of Strychnos trinervis (Vell.) Mart. (Loganiaceae). AB - Bisnordihydrotoxiferine, a dimeric tertiary indole alkaloid obtained from the root bark of Strychnos trinervis (Vell.) Mart. (Loganiaceae), inhibited normal defaecation and castor oil, arachidonic acid, and magnesium sulphate-induced diarrhoea on intraperitoneal administration in mice. The effect may be related to the ability of the compound to decrease normal and castor oil-stimulated gastric emptying, small intestinal transit and water and electrolyte accumulation, and inhibition of normal colonic transit. As prostaglandins are involved in gastrointestinal functions, inhibition of their synthesis is likely to contribute to the anticathartic activity, which has never been reported before for an indole alkaloid. PMID- 2896790 TI - The structure of phenindamine base and salts in the solute state. AB - High-field NMR (13C and 1H) studies of phenindamine are reported which establish structures of the free base and some of its salts in the solute condition. The base exists as a mixture of two isomers which differ in double bond position (9 9a or 4a-9a) while most salts are 9-9a isomers. The clinically employed tartrate (Thephorin) is exceptional in being a 4a-9a ene. Salts of both double bond type exist in solution as mixtures of protonated epimers of variable epimeric ratio, that of the tartrate in D2O being approximately 1:1. PMID- 2896791 TI - Pulmonary clearance of vasoactive drugs: N-oxidation of SK&F 86466 in the isolated perfused rat lung. AB - The contribution of the lung to the systemic clearance of the alpha receptor antagonist SK&F 86466 in rats was determined using the isolated perfused rat lung. Lungs were perfused with a blood-free medium containing SK&F 86466 at initial concentrations ranging from 0.26 to 5.1 microM at a flow rate of 104 ml/min. During the perfusion the concentration of SK&F 86466 in the perfusion medium declined monoexponentially. The half-life (8.0 +/- 1.8 min), steady state volume of distribution (205 +/- 16 ml), clearance (18.3 +/- 2.4 mL/min) and extraction ratio (0.18 +/- 0.02) were independent of the initial concentration of SK&F 86466. The free fraction of SK&F 86466 in the perfusion medium, determined by equilibrium dialysis, was 0.598. The average intrinsic clearance of SK&F 86466 in the lung, calculated using the flow rate, free fraction and clearance, was 37.4 ml/min. The concentration of the N-oxide metabolite of SK&F 86466 (SK&F 102102) in the perfusion medium increased with time, and at the end of the perfusion was approximately equal to the initial concentration of SK&F 86466. The pharmacokinetics of SK&F 86488 in lungs from rats pretreated with the suicide substrate inhibitor of cytochrome P-450 1-aminobenzotriazole were identical to the kinetics in lungs from control animals. The pretreatment regimen used reduced the activity of ethoxycoumarin-O-deethylase in lung microsomes by 70% and reduced P-450 content to below the limit of detection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896792 TI - Antihistaminic and antimuscarinic effects of amitriptyline on guinea pig ileal electrolyte transport and muscle contractility in vitro. AB - Amitriptyline, a tricyclic antidepressant, was tested for antimuscarinic and antihistamine effects against bethanechol and histamine-stimulated contractility and secretion in the guinea pig ileum in vitro. Comparisons were made with muscarinic-receptor antagonists, as well as with H1 and H2 histamine-receptor antagonists. Amitriptyline (0.01-5.0 microM) produced a parallel rightward shift in the concentration-response curves to histamine in muscle (Ki 0.4 nM) and mucosa (Ki 450 nM). The H1-receptor antagonists pyrilamine and diphenhydramine were less potent against histamine in the muscle and more potent against histamine in the mucosa than was amitriptyline. The H2-receptor antagonist cimetidine was ineffective in the muscle and mucosa. Amitriptyline (0.1-2 microM) also produced a parallel rightward shift in the concentration-response curve to bethanechol in muscle (Ki 133 nM) and mucosa (Ki 143 nM). Against bethanechol, in both tissues, atropine and 4-diphenylacetoxy-N-methyl piperidine methiodide were more potent competitive antagonists than was amitriptyline. Pirenzepine produced a competitive blockade of bethanechol in the muscle and a noncompetitive blockade in the mucosa. The data indicate that amitriptyline exerts more potent antihistaminic effects on guinea pig ileal muscle than the mucosa but that the tricyclic drug is equipotent as an antimuscarinic in both tissues. PMID- 2896793 TI - Behavioral effects of histamine H1 antagonists: comparison with other drugs and modification by haloperidol. AB - The behavioral effects of several histamine H1 antagonists were compared in groups of squirrel monkeys trained to respond under fixed-interval schedules involving response-produced shock or termination of a stimulus associated with shock. Low to intermediate doses of the conventional H1 antagonists chlorpheniramine (up to 3.0 mg/kg), diphenhydramine (up to 1.0 or 3.0 mg/kg), pyrilamine (up to 3.0 mg/kg) and tripelennamine (up to 0.3 or 1.0 mg/kg) produced dose-related increases in response rate under all conditions in which they were studied; higher doses either increased responding less or decreased it. In contrast, a wide range of doses of the novel H1 antagonists AHR 11325 (1.0-30.0 mg/kg), astemizole (up to 10.0 mg/kg) and loratadine (up to 17.0 mg/kg) usually had little effect on responding, although decreases in response rate accompanied by emesis were observed after the highest doses in some monkeys. Other H1 antagonists including phenindamine (0.03-17.0 mg/kg), promethazine (0.03-5.6 mg/kg) and terfenadine (0.1-10.0 mg/kg) had different effects in individual subjects (i.e., dose-related increases in response rate in some monkeys and either little change or dose-related decreases in responding in other monkeys). The dopamine uptake inhibitors cocaine (0.01-1.0 mg/kg) and bupropion (0.1-10.0 mg/kg) had behavioral effects similar to those of chlorpheniramine, diphenhydramine, pyrilamine and tripelennamine, whereas the muscarinic antagonist atropine (0.03-1.0 mg/kg), the serotonin 5-hydroxytryptamine/5-hydroxytryptamine antagonist cyproheptadine (0.03-1.0 mg/kg), the norepinephrine uptake inhibitor desmethylimipramine (0.03-3.0 mg/kg) and the benzodiazepine diazepam (0.3-30.0 mg/kg) produced only dose-related decreases in response rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2896794 TI - Tetrazepam: a benzodiazepine which dissociates sedation from other benzodiazepine activities. I. Psychopharmacological profile in rodents. AB - In the 1,4-benzodiazepine (BZD) series the nature of the C(5) substituent is critical for activity. In tetrazepam this substituent is a cyclohexenyl ring, in all other clinically effective 1,4-BZD derivatives it is a phenyl ring. The activities of tetrazepam and diazepam, whose chemical structures differ only by the nature of the C(5) substituent, were compared in rodent models which are predictive of anticonvulsant, anxiolytic, muscle relaxant and sedative effects. In mice, tetrazepam and diazepam antagonized pentylenetetrazol (PTZ)-induced seizures, increased novel food consumption, decreased rearing behavior in the Staircase test and impaired performance in the Traction test. The effects of both drugs were abolished by Ro 15-1788. In rats, both drugs antagonized PTZ-induced seizures, released punished responding in an approach-avoidance conflict procedure and blocked the PTZ discriminative cue. In mice and rats, and with both BZDs, maximal activity occurred 15 to 30 min after drug administration. In mice and rats, the overall anxiolytic and muscle relaxant potencies of tetrazepam were one-fourth and one-sixth those of diazepam, respectively. The anticonvulsant potency of tetrazepam varied from one-half (rats) to one-twentieth (mice) that of diazepam. In rats and mice, the sedative potency of tetrazepam (Rotorod test; locomotor activity) was approximately one-sixteenth that of diazepam. Finally, tetrazepam induced a loss of righting reflex in mice, with an ED50 value which was approximately 70-times greater than that of diazepam. It is concluded that replacing the 5-phenyl ring by a 5-cyclohexenyl ring leads to a relative dissociation of the pharmacological actions of the 1,4-BZDs. PMID- 2896795 TI - Tetrazepam: a benzodiazepine which dissociates sedation from other benzodiazepine activities. II. In vitro and in vivo interactions with benzodiazepine binding sites. AB - Tetrazepam is a 1,4-benzodiazepine (BZD) derivative which, in rodents, appears to have very little sedative and ataxic effects. In an attempt to identify the molecular mechanisms underlying this particular pharmacological profile we examined the interaction of tetrazepam with BZD binding sites. Tetrazepam interacted competitively with "central" and "peripheral" BZD binding sites and exhibited comparable affinities for both sites. Tetrazepam was approximately one seventh as potent as diazepam at the central receptor and as potent as diazepam at the peripheral binding site. Tetrazepam did not distinguish type I from type II central BZD receptors, as evidenced by comparable affinities for the cerebellar and hippocampal receptors. In vitro autoradiographic studies showed that tetrazepam displaced [3H]flunitrazepam from rat brain membranes without any clear regional specificity. Like all BZD receptor agonists, tetrazepam exhibited a gamma-aminobutyric acid shift, a photoaffinity shift and potentiated the binding of 35S-t-butyl-bicyclophosphorothionate to rat brain membranes. However, the latter effect was observed at relatively high concentrations of tetrazepam. In vivo, tetrazepam displaced specifically bound [3H]flunitrazepam from mouse brain (ID50, 37 mg/kg p.o. vs 3.5 mg/kg p.o. for diazepam) and from mouse kidney (ID50, 38 mg/kg p.o. vs. 21 mg/kg p.o. for diazepam). It is concluded that tetrazepam is a BZD receptor agonist; the molecular mechanisms which underly the low sedative potential of the drug cannot at present be explained by a particular interaction with either central or peripheral BZD binding sites, but may be related to the drug's relatively weak effect on 35S-t-butyl bicyclophosphorothionate binding. PMID- 2896796 TI - Hay fever treatments--which should be tried first? AB - A series of comparative trials on nine popular and pharmacologically distinct regimens for the treatment of hay fever was undertaken in the course of normal general practice in the pollen seasons of 1981-83. One hundred and forty doctors recruited 640 patients to assess the overall usefulness of the treatments on daily diaries. ;Usefulness' was scored on a linear analogue scale weighing up the degree of hay fever symptoms during treatment, side effects and ease of use of the preparation.The regimen with the highest overall usefulness score was beclomethasone diproprionate with sodium cromoglycate eye drops (Beconase and Opticrom). Although the score was not significantly higher than those for methylprednisolone acetate (Depo-Medrone), astemizole (Hismanal) or terfenadine (Triludan), Beconase/Opticrom scored significantly better than mequitazine (Primalan), chlorpheniramine maleate (Piriton), sodium cromoglycate nasal insufflation with xylometazoline/antazoline eye drops (Rynacrom and Otrivine Antistin) and azatadine maleate (Optimine). Beconase/Opticrom was first in rank order with respect to all the other regimens for the treatment of both mild and severe hay fever. Dimethothiazine (Banistyl), also shown to be useful, has since been withdrawn from prescription. PMID- 2896797 TI - Long-term benzodiazepine use. PMID- 2896798 TI - Martsolf's syndrome in a non-Jewish boy. AB - Martsolf's syndrome has been described in Jewish people. We describe a patient of non-Jewish ancestry who has minor differences from other patients. The possible pattern of inheritance is discussed. PMID- 2896799 TI - Meeting highlights: William Guy Forbeck Foundation think tank on "multidrug resistance in cancer chemotherapy". PMID- 2896800 TI - Electrophoretic analysis of P-glycoproteins produced by mouse J774.2 and Chinese hamster ovary multidrug-resistant cells. AB - P-glycoprotein (P-gp) plays a fundamental role in multidrug resistance. The quantity of P-gp relates to the degree of drug resistance. A comparison was made between P-gps in mouse and hamster cell lines in both Laemmli and modified Fairbanks gel systems. Both proteins are derived from precursors of similar size that undergo differential N-linked glycosylation. The electrophoretic mobility and the amount of P-gp are remarkably dependent on the conditions of analysis. Notably, boiling P-gp before Laemmli gel electrophoresis decreases its mobility by an amount that is equivalent to approximately equal to 15 kDa and results in an apparent diminution in the amount of protein. The latter effect can give a false impression concerning the quantity of P-gp in cells. PMID- 2896801 TI - Glutamate and kainate effects on the noradrenergic neurons innervating the rat vas deferens. AB - The effects of glutamate on the noradrenergic innervation of the rat vas deferens have been investigated. Administration of a single dose of kainate (50 micrograms) to the peripheral noradrenergic ganglia innervating the vas deferens induced a time-dependent decrease of norepinephrine in the organ; after 10 days the norepinephrine concentration had fallen to 35% of control values. This effect was accompanied by a 70% decrease in the potassium-induced release of recently incorporated 3H-norepinephrine. Concomitantly, postsynaptic hypersensitivity to both norepinephrine and dopamine appeared. The finding that adrenergic ganglia possess high-affinity glutamate binding sites suggests that the effect of kainate may be ascribed to glutamate receptors present on the perikarya of the noradrenergic neurons. It is concluded that noradrenergic neurons of the vas deferens are under glutamatergic control and that this might be important in the motor control of the organ. PMID- 2896802 TI - Togavirus-associated pathologic changes in the midgut of a natural mosquito vector. AB - Arthropod-borne viruses were not previously believed to cause discernible pathologic changes in their natural mosquito vectors. We report cytopathologic lesions in the midgut of the mosquito, Culiseta melanura, 2 to 5 days after oral infection with eastern equine encephalomyelitis virus. Sloughing of densely staining, heavily infected epithelial cells into the midgut lumen was observed by light and transmission electron microscopy, along with degeneration of cells within the epithelium. Pathological changes in midgut epithelial cells sometimes included loss of brush border and basal lamina integrity. Disruption of the midgut basal lamina could result in bypassing of barriers to virus dissemination within the mosquito and allow rapid transmission to occur. Alternatively, luminal sloughing of heavily infected midgut epithelial cells may serve to modulate mosquito infections. These findings challenge previous beliefs regarding the benign nature of arbovirus-invertebrate host relationships. PMID- 2896803 TI - [HBV, HIV and HTLV-I infection control by medical technologists]. PMID- 2896804 TI - Deoxyribonucleic acid (DNA) polymorphism in the apolipoprotein AI gene: a study in a Japanese population. AB - A Japanese group comprising 54 hyperlipidemic and 73 normolipidemic subjects were genotyped for DNA restriction fragment length polymorphisms (RFLPs) at the apoAI CIII gene locus. The polymorphisms with Sstl were present at allelic frequencies of 0.63 (S1 allele) and 0.37 (S2 allele). Unlike the previously reported associations of the S2 allele with hypertriglycedemia found in Caucasians there was no difference in the frequency of S2 allele between normolipidemic and hyperlipidemic Japanese subjects. No significant association of genotypes were observed with serum levels of lipids and apolipoproteins, except for the association of the S2 allele with the higher mean level of HDL-cholesterol. In addition, among 26 patients who had coronary artery disease (CAD), as documented by angiography, there was no significant difference in the distribution of polymorphic alleles between CAD patients and normolipidemic control subjects. PMID- 2896805 TI - Augmentation and inhibition of beta-adrenergic agonists-stimulated tissue cyclic AMP accumulation by alpha-adrenergic agonists in rat parotid gland. AB - It was found that phenylephrine and methoxamine had two effects (one was inhibitory and the other was augmentative) on isoproterenol-stimulated cyclic AMP in rat parotid slices. The augmentation was abolished by alpha-adrenergic antagonists or by omission of calcium in the medium. Cyclic AMP accumulation by norepinephrine (NE) was significantly decreased by omission of calcium in the medium. Calmodulin antagonists, trifluoperazine and W-7, decreased NE-induced cyclic AMP accumulation, but another calmodulin antagonist, carmidazolium, did not. Phorbol ester such as 4 beta-phorbol 12-myristate, 13-acetate and phorbol 12, 13-dibutyrate, did not augment the effect of isoproterenol. These results suggest that although the influx of calcium is required in the alpha-adrenergic agonists-induced augmentation, calmodulin and protein kinase C may not be intermediates in this process. Calcium ions (10(-7) and 10(-6) M) slightly increased the activity of adenylate cyclase, but calcium (10(-6)-10(-4) M) dose dependently inhibited the effect of isoproterenol. Therefore, calcium ions do not participate in the augmentation by directly modulating the activity of adenylate cyclase. The inhibitory effect was not affected by alpha-adrenergic antagonists. The activation of adenylate cyclase by isoproterenol was inhibited by phenylephrine with higher inhibition being obtained in lower concentrations of isoproterenol. Phenylephrine in the presence of isobutylmethylxanthine increased the amount of cyclic AMP and this effect was inhibited by propranolol, but not by phentolamine. [3H]-CGP 12177 binding of the parotid membrane was inhibited by alpha-adrenergic antagonists. These results suggest that the inhibitory effect of phenylephrine and methoxamine may be mediated by beta-adrenergic receptor. PMID- 2896806 TI - The effect of H2-receptor antagonists on antipyrine and pentobarbital metabolism in male and female rats. AB - Pretreatment of male and female rats with cimetidine decreased the amount of 3 hydroxymethylantipyrine in the 24-hr urine, but urinary antipyrine and 4 hydroxyantipyrine were increased compared to that of the corresponding control rats. On the other hand, the amount of norantipyrine and the total amount of antipyrine and its metabolites were not changed by cimetidine, ranitidine and famotidine. These data suggest that ranitidine and famotidine have little effect on the microsomal mixed function oxidase system in male and female rats. PMID- 2896807 TI - Effect of N-N'-diphenyl-p-phenylenediamine pretreatment on urinary enzyme excretion in cisplatin nephrotoxicity in rats. AB - Two days after cisplatin was injected into rats, urinary N-acetyl-beta-D glucosaminidase (NAG) and gamma-glutamyltranspeptidase (gamma-GTP) activities increased. The urinary excretion of NAG continued to rise until 4 days after the injection of cisplatin, the last day examined. However, the increase in urinary gamma-GTP excretion which lasted for 2 days returned to its control level 4 days after cisplatin injection. The alkaline phosphatase activity in urine was unaffected by cisplatin injections. The antioxidant N-N'-diphenyl-p phenylenediamine attenuated these increases in enzyme activities caused by cisplatin. The results of this study suggest that monitoring the change in urinary activities of some enzymes is the method of choice for detecting cisplatin nephrotoxicity and that the increase may involve the generation of free radicals by cisplatin. PMID- 2896808 TI - Plasma growth hormone-releasing hormone levels in type 1 (insulin-dependent) diabetic children following a mixed meal. AB - Following a mixed meal, plasma hormone responses were measured in four type 1 diabetic children and in eight short normal children. Between 60 and 150 min after ingestion of the mixed meal there was a significant increase in circulating growth hormone-releasing hormone values both in diabetic and in normal children. Mean plasma GHRH peak values were not different between diabetic patients (27.0 +/- 3.9 ng/l) and controls (24.6 +/- 4.9 ng/l). No time relationship to spontaneous growth hormone peaks was observed. Whereas normal children showed a characteristic biphasic plasma somatostatin response, somatostatin plasma levels in diabetic children did not change. In normal children plasma insulin values increased between 30 and 150 min, but remained unchanged in type 1 diabetic patients. Blood glucose response was more pronounced in diabetic children than in short normal children. These results indicate that circulating growth hormone releasing hormone does not play a dominant role in the regulation of insulin and somatostatin. PMID- 2896809 TI - Spreading depression and central nervous system pharmacology. AB - Spreading depression is a reversible response of brain tissue to a local insult. It has been postulated to be the physiological substrate for the aura phase of classic migraine. The properties and mechanisms of spreading depression were studied in the parietal neocortex of the alfentanil-anesthesized rat, by using a cup electrode that provided close control of the electrical stimulus while allowing specific ion (K+) and potential recordings to be made directly beneath the cathode, the region of origin of the stimulus-induced spreading depression. Cathodal stimulation caused the extracellular K+ concentration to rise, and spreading depressions were observed when this concentration exceeded 8-12 mM in the upper 100-200 microns of cortex. In some experiments extracellular [K+] continued to increase for 5-10 sec after termination of the stimulus, without detectable after-discharge in the potential record, before subsiding. While spreading depression could easily be induced by pressure on the cortex, local damage incidental to opening the dura rarely induced spreading depression. This suggests that a local (1-mm2) neurovascular injury is not likely to induce spreading depression--at least in normal cortex--and so is probably not the source of the spreading depression postulated to generate the aura of classic migraine. Mechanisms of spreading depression, and drugs that influence spreading depression, are reviewed, and possible uses of spreading depression in the pharmacology of the central nervous system are considered. PMID- 2896810 TI - Survival in acute myeloblastic leukemia is not prolonged by remission maintenance or early reinduction chemotherapy. The Toronto Leukemia Study Group. AB - A role for post-induction chemotherapy for adult patients with acute myeloblastic leukemia in remission has not been established. We have studied 125 patients with acute myeloblastic leukemia in complete remission to determine the effect on survival of remission maintenance therapy and of early reinduction therapy given at the time of predicted imminent relapse. Following remission induction with 6 thioguanine, cytosine arabinoside and daunorubicin (TAD), all patients received consolidation therapy with these same three drugs. Forty-three patients were randomized to arm A, continuing chemotherapy; 40 patients were randomized to arm B, no further chemotherapy until morphological relapse; and 42 patients were randomized to arm C, no further chemotherapy until an increase in myeloblast associated antigens was detected in bone marrow by means of antimyeloblast heteroantisera. The median durations of complete remission, age adjusted, for the three groups are not significantly different: 15.7 months for group A, 16.2 months for group B and 14.1 months for group C. The age adjusted median survivals for the three groups are also not significantly different: 17.6 months for group A, 21.8 months for group B and 18.8 months for group C. Quality of life was determined to be superior for patients having no further maintenance therapy (arms B and C). We conclude that our patients receiving induction and consolidation therapy with TAD did not benefit from remission maintenance or early reinduction chemotherapy, and had an improved quality of life if no maintenance therapy was given. PMID- 2896811 TI - Percutaneous absorption of cyclosporin. PMID- 2896812 TI - Cannabis and schizophrenia. PMID- 2896813 TI - Conservative management of prostate cancer. PMID- 2896814 TI - Hypertension in diabetes. PMID- 2896815 TI - Campylobacter pylori urease: a new serological test. PMID- 2896816 TI - Osteoporosis. PMID- 2896817 TI - Failure of both insulin-delivery system and ward-based blood glucose assessment. PMID- 2896818 TI - Renal replacement therapy for diabetics. PMID- 2896819 TI - Safety of "topical" lignocaine. PMID- 2896820 TI - Dicyclomine for idiopathic dyspepsia. PMID- 2896821 TI - Direct intraperitoneal insemination. PMID- 2896822 TI - Symptomatic Chlamydia psittaci reinfection. PMID- 2896823 TI - A baby's life or a mother's liberty: a United States case. PMID- 2896825 TI - No neuropsychological abnormalities in healthy HIV-positive people. PMID- 2896824 TI - National Institute of Communicable Diseases. PMID- 2896826 TI - Placebo-controlled trial of two acellular pertussis vaccines in Sweden- protective efficacy and adverse events. Ad Hoc Group for the Study of Pertussis Vaccines. AB - 3801 children aged 5-11 months were entered into a blind placebo-controlled trial of pertussis vaccine. 954 were randomised to receive placebo (vaccine solvent), 1419 to receive a two-component vaccine containing formaldehyde detoxified lymphocytosis promoting factor (LPF) and filamentous haemagglutinin, and 1428 to receive an LPF-toxoid vaccine. After 7-13 weeks 3724 infants received a second dose. Immediate side-effects were mild. Small local reactions occurred more often in the vaccinated infants than in those who received placebo, especially after the second dose of the two-component vaccine. During 15 months of follow-up from 30 days after the second dose, culture-confirmed whooping cough (cough and a positive culture of Bordetella pertussis) occurred in 40 placebo, 27 LPF-toxoid vaccine, and 18 two-component vaccine recipients. The point estimate of protective efficacy was 54% (95% confidence intervals 26-72%) for the LPF-toxoid vaccine and 69% (47-82) for the two-component vaccine; protection against culture confirmed whooping cough of over 30 days duration was 80% (59-91%) and 79% (57 90%), respectively. PMID- 2896827 TI - Epithelioid haemangioma-like vascular proliferation in AIDS: manifestation of cat scratch disease bacillus infection? AB - Papular and nodular skin lesions that clinically resembled Kaposi sarcoma, but histologically showed a distinct epithelioid haemangioma-like appearance, were noted in seven patients with the acquired immunodeficiency syndrome. Clusters of bacteria that had the structure of gram-negative rods were identified within each of the vascular proliferations by electron microscopy. The bacteria did not stain with the Brown-Brenn, acid-fast, or other histochemical stains for infectious organisms, but did stain with Warthin-Starry--ie, the staining profile was that described for the cat scratch disease (CSD) bacillus. Immunoperoxidase staining, using antisera raised in rabbits against cultured CSD bacillus, showed a positive reaction with the bacterium in all five cases tested. The two surviving patients have both given histories of having been scratched by a cat. In several patients, the vascular lesions regressed after therapy with antibiotics appropriate for CSD bacillus infection. PMID- 2896828 TI - Effects of dose and strain of vaccine on success of measles vaccination of infants aged 4-5 months. AB - Small-scale trials of the Edmonston-Zagreb (E-Z) measles vaccine were undertaken to determine the dose necessary to immunise 4-6-month-old infants. Antibody responses, measured 16 weeks after vaccination, were dose dependent: 40,000 plaque forming units given subcutaneously resulted in positive responses in all infants and higher antibody levels than doses of 20,000 or 10,000 units (10,000 units gave a failure rate of 25%). In further trials the E-Z vaccine was compared with the Schwarz vaccine, both being given in subcutaneous doses of 40,000 plaque forming units. In infants aged 20 weeks the E-Z vaccine produced higher levels of measles antibody and in those aged 18 weeks its superiority showed in a lower proportion failing to respond (3 of 39 versus 19 of 35). PMID- 2896829 TI - Galactosylation of IgG associated oligosaccharides: reduction in patients with adult and juvenile onset rheumatoid arthritis and relation to disease activity. AB - The prevalence of agalactosyl N-linked oligosaccharides on serum IgG was determined for patients with juvenile onset and with adult rheumatoid arthritis. A significant difference in the prevalence of these structures from age matched controls was found in both types of arthritis. In patients with adult onset rheumatoid arthritis, the results showed a strong correlation between the prevalence of IgG-associated agalactosyl oligosaccharides and disease activity. A correlation between disease activity and agalactosyl structures was also seen in a retrospective analysis of serial IgG samples from patients with juvenile onset disease. The finding that childhood onset arthritis and adult rheumatoid arthritis share a defect of glycosylation of serum IgG suggests that there may be a greater similarity between these two varieties of rheumatoid arthritis than has been hitherto considered. The observation that the incidence of agalactosyl oligosaccharides on IgG fluctuates with disease activity provides indirect evidence for a seminal role for this change of glycosylation in the inflammatory process which, in rheumatoid arthritis, is focused on the synovial tissues and results in bone erosions and joint destruction. PMID- 2896831 TI - The Y chromosome and sex determination. PMID- 2896830 TI - Tumour necrosis factor as an autocrine tumour growth factor for chronic B-cell malignancies. AB - Recombinant tumour necrosis factor (TNF) promotes survival and induces proliferation in the tumour cells from two malignancies of B lymphocytes--hairy cell leukaemia and B-chronic lymphocytic leukaemia. Culture with TNF also induces TNF mRNA and protein, so the cytokine may act as an autocrine tumour growth factor. These growth promoting effects are antagonised by alpha but not by gamma interferon. PMID- 2896832 TI - TWAR--Chlamydia in a new guise? PMID- 2896833 TI - Present day practice in infant feeding. PMID- 2896834 TI - Orofacial manifestations of HIV infection. PMID- 2896835 TI - Does topical tretinoin prevent cutaneous ageing? PMID- 2896836 TI - New life for the EEG. PMID- 2896837 TI - Prevalence of angina as assessed by a survey of prescriptions for nitrates. AB - Prescriptions for nitrates issued during a 6-month period in the Nottingham Health District were used to estimate the prevalence of patients thought to have angina who might potentially require specialist investigation and treatment. The 15,451 prescriptions issued were for 6856 patients. Of these, only 435 were known to hospitals. The general practitioner records of 499 patients identified from a 10% sample of general practitioners showed that in 96% the general practitioner had prescribed a nitrate for the treatment of angina. The records of five large practices with some form of diagnostic register suggested, however, that the survey detected only 73% of patients thought to have angina. With these estimates of specificity and sensitivity the prevalence of angina in Nottingham was calculated to be 1.5%. Few of the patients identified had been investigated in detail, and only 26% had attended hospital in the 3 years before the survey. There is clearly a very large potential demand for hospital resources for the investigation and treatment of angina. PMID- 2896838 TI - Use of oxygen therapy for adult patients outside the critical care areas of a university hospital. AB - To obtain data on oxygen use among hospital inpatients criteria for instituting, monitoring, and stopping oxygen therapy were formulated. The records of 90 consecutive patients who had been started on oxygen therapy outside the critical care areas of a university hospital were then examined. By the criteria, 79% of patients were deemed to have required oxygen therapy, 14.5% had been adequately monitored, and only 12% had had therapy terminated on the basis of appropriate physiological measurements. Prospective studies are required to validate monitoring recommendations and establish their cost-benefit ratio in terms of patient comfort and health-care costs. PMID- 2896840 TI - The obligation to ask for organs. PMID- 2896839 TI - Ten-year results of renal transplantation with azathioprine and prednisolone as only immunosuppression. AB - 93 patients received 102 renal transplants between 1968 and 1977. 99 grafts were from cadavers and 3 were from live donors; 93 were first grafts, 7 were second, and 2 were third. At 10 years total actual patient survival was 66.6%. 50 (55.5%) of 90 first cadaver grafts, and 52.2% of all cadaver grafts, survived at 10 years. Cardiovascular disease was the commonest cause of death, being responsible for 18 of 31 deaths (58%). PMID- 2896841 TI - Mischievous morality. PMID- 2896842 TI - Human papillomavirus preceding intraepithelial neoplasia in serial cervical smears. PMID- 2896843 TI - Magnesium, beta-agonists, and asthma. PMID- 2896844 TI - Transdermal glyceryl trinitrate and lumbar sympathectomy. PMID- 2896845 TI - Hepatitis B virus type 2. PMID- 2896846 TI - Cytomegalovirus and atherosclerosis. PMID- 2896847 TI - CT scan policy in assessment of dementia. PMID- 2896848 TI - Dental effects of infants' fruit drinks. PMID- 2896849 TI - Intestinal infection with Campylobacter in children. PMID- 2896850 TI - Red wine headache. PMID- 2896851 TI - Sequential benign sexual headache and exertional headache. PMID- 2896852 TI - Group A beta-haemolytic Streptococcus causing disseminated intravascular coagulation and maternal death. PMID- 2896853 TI - Fastidious anaerobes and cryptogenic brain abscesses. PMID- 2896854 TI - Mild Lyme disease. PMID- 2896855 TI - Antibiotic resistance in Pseudomonas pseudomallei. PMID- 2896856 TI - Cause of finger clubbing. PMID- 2896857 TI - Obesity and hypertension. PMID- 2896858 TI - Epithelioid angiomatosis in HIV infection: neoplasm or cat-scratch disease? PMID- 2896859 TI - False positive anti-HIV tests with Wellcome kits. PMID- 2896860 TI - Drug abuse and mental illness. PMID- 2896861 TI - Anal signs in haemolytic uraemic syndrome. PMID- 2896862 TI - Project HOPE in Grenada. PMID- 2896863 TI - Health services in the occupied territories. PMID- 2896864 TI - Orthogeriatric liaison. PMID- 2896865 TI - Junior doctors' standard of care. PMID- 2896866 TI - Improvement in the erythropoiesis of chronic haemodialysis patients with desferrioxamine. AB - 16 chronic haemodialysis patients (group I), with non-microcytic anaemia (mean haemoglobin 7.2 g/dl, SD 1.0, range 5.8-9.8), moderate aluminium overload (serum aluminium 44 micrograms/l, SD 16, range 21-74), and normal or high iron stores (ferritin 800 micrograms/l SD 464, range 34-2013) were treated with intravenous desferrioxamine 1 g at the end of each dialysis for six months. 8 patients with similar characteristics served as controls (group II). After six months group I showed a rise in haemoglobin to 9.1 (SD 2.5) g/dl and a decrease in blood transfusion requirements, both significant, whereas group II showed no changes. Other significant changes observed in group I, but not group II, were a rise in reticulocytes and in red cell creatine and a fall in red cell protoporphyrin and serum ferritin. Ferritin decreased more in the patients whose anaemia improved. Minor increases in serum aluminium in group I did not differ from those in the control group. Desferrioxamine may benefit the anaemia of chronic haemodialysis patients through improvement of erythropoiesis. The effect seems not to be related to chelation of a heavy aluminium overload. PMID- 2896867 TI - Aluminium chelation therapy in dialysis patients: evidence for inhibition of haemoglobin synthesis by low levels of aluminium. AB - To investigate the possibility that aluminium may exacerbate anaemia in dialysis patients with only modest aluminium accumulation, 15 patients whose exposure to aluminium had been low were treated for three months with the aluminium chelating agent desferrioxamine, 30 mg/kg intravenously at the end of each dialysis session. Serum aluminium concentrations before treatment were 5-125 micrograms/ml. After one month of desferrioxamine, serum aluminium (including the chelate) had risen from 54.6 (SEM 11.2) to 167.0 (27.5) micrograms/l; and after three months haemoglobin had risen from 8.46 (0.70) to 10.43 (0.80) g/l. Mean cell volume and mean cell haemoglobin concentration also increased significantly. The maximum rise in haemoglobin correlated with the patients' aluminium burden as estimated by the mean serum aluminium concentration after one month of desferrioxamine therapy (r = 0.85). The greatest response to desferrioxamine occurred in patients with a baseline serum aluminium of 15-75 micrograms/l (mean increase in haemoglobin 38%). The results indicate that even the modest aluminium accumulation found in most dialysis patients has a pronounced inhibitory effect on haemoglobin synthesis. The possible toxic effect of aluminium should be considered in all anaemic dialysis patients. PMID- 2896868 TI - Pilot trial of branched-chain aminoacids in amyotrophic lateral sclerosis. AB - 22 patients with amyotrophic lateral sclerosis were entered into a double-blind, randomised, placebo-controlled trial of treatment with branched-chain aminoacids. 11 received daily 12 g L-leucine, 8 g L-isoleucine, and 6.4 g L-valine, by mouth, and the remainder received placebo. During the one-year trial, patients in the placebo group showed a linear decline in functional status consistent with the natural history of the disease. Those treated with aminoacids showed significant benefit in terms of maintenance of extremity muscle strength and continued ability to walk. PMID- 2896869 TI - Noradrenaline response to edrophonium in primary autonomic failure: distinction between central and peripheral damage. AB - The effects of intravenous edrophonium on plasma noradrenaline were studied in 12 subjects with primary autonomic failure. 5 had clinical features of central autonomic damage, 4 with parkinsonism (PD) and 1 with multiple system atrophy (MSA); the other 7 had clinical features of progressive autonomic failure without detectable central neurological damage (PAF). After edrophonium all but 1 subject showed falls in heart rate of about 6 beats/min; there were no consistent blood pressure changes. The 5 PD/MSA patients all had normal plasma noradrenaline responses to edrophonium, with rises of 35-66% within 2-8 min of injection. 6 of the 7 PAF patients had no response or very small responses (-6 to +11%), while the other subject had a normal response (70% rise). The noradrenaline response to edrophonium may provide a simple way to differentiate between central and peripheral autonomic damage. PMID- 2896870 TI - Type III procollagen peptide: a marker of disease activity and prognosis in primary biliary cirrhosis. AB - The prognostic value of the aminoterminal propeptide of type III procollagen (P3NP) was investigated in 63 patients with primary biliary cirrhosis (PBC) followed for up to 87 months. No patient with an initially normal serum P3NP level died during the study; survival was significantly worse with increasing serum P3NP levels. Cox multivariate analysis confirmed that serum P3NP was an independent prognostic variable. Positive correlations were found between serum P3NP and histological stage, pericellular fibrosis, piecemeal necrosis, and serum concentrations of alanine aminotransferase and aspartate aminotransferase. Raised P3NP levels also correlated with the degree of cholestasis as evaluated by serum bilirubin, serum alkaline phosphatase, and copper binding protein deposition in the liver. Serum P3NP is of prognostic value because it reflects the major pathophysiological features of PBC. PMID- 2896871 TI - Suction chamber protection for endoscope biopsy-channel valves. PMID- 2896872 TI - HIV-2 in perspective. PMID- 2896873 TI - What causes oedema? PMID- 2896874 TI - A College of Paediatricians? PMID- 2896875 TI - Cerebellar stroke. PMID- 2896876 TI - Leg lengthening in achondroplasia. PMID- 2896877 TI - Raised venous pressure: a direct cause of renal sodium retention in oedema? AB - Contemporary theories of oedema formation are often based on the idea that "effective" blood volume is reduced, and that sodium retention and oedema are a result of the kidney responding, as in haemorrhage, to a perception by receptors in the circulation that blood volume is inadequate. This idea has enhanced understanding of the pathophysiology of such conditions as cardiac failure and cirrhosis, but has obscured the fact that blood volume is almost always increased in oedematous states. Evidence is presented that an increase in renal venous pressure can cause sodium retention by a direct action on the kidney: a rise in venous pressure could thereby initiate a vicious circle by causing sodium retention, expansion of plasma volume, and further increase in venous pressure. This sequence of events may be crucial in the pathophysiology of cor pulmonale, and an exacerbating factor in other oedematous states. PMID- 2896878 TI - Role of arterial pressure in the oedema of heart disease. AB - The primary function of the heart is maintenance of the arterial pressure that is essential for perfusion of the tissues. Cardiac output is mainly regulated by control systems acting through the arterial pressure, whereby the heart matches its output to the perfusion of the tissues, in which blood is distributed according to local vascular resistances. When the heart is disabled, the body intensifies to an abnormal degree the renal, nervous, and endocrine mechanisms through which arterial pressure is maintained. As a result, the kidneys retain excess salt and water; the volume of extracellular liquid, including the plasma, expands; and the systems that limit the blood volume are overridden. PMID- 2896879 TI - Epidemic multiresistant Escherichia coli infection in West Lambeth Health District. AB - A year-long outbreak of multiresistant Escherichia coli K52 H1, predominantly serogroup O15, is reported from south east London. Most patients had urinary tract infections, some with septicaemia; but some cases of septicaemia were associated with pneumonia, meningitis, and endocarditis--unusual infections for E coli. 3 of these patients died. The organism was acquired in the community, and its source is still being investigated. PMID- 2896880 TI - Pensive women, painful vigils: consequences of delay in assessment of mammographic abnormalities. PMID- 2896881 TI - Breast cancer, tamoxifen, and surgery. PMID- 2896882 TI - Radiation-induced cancer risks. PMID- 2896883 TI - Chagas' myocarditis imported into France. PMID- 2896884 TI - Fish oil supplementation. PMID- 2896885 TI - Bone histology in renal transplant patients receiving cyclosporin. PMID- 2896886 TI - Anaemia, ferritin, and vitamins in continuous ambulatory peritoneal dialysis. PMID- 2896887 TI - Prevalence of toxocaral disease. PMID- 2896888 TI - Necrotising myopathy and zidovudine. PMID- 2896889 TI - Fusidic acid, HIV, and host cell toxicity. PMID- 2896890 TI - Declining levels of HIV P24 antigen in serum during treatment with foscarnet. PMID- 2896892 TI - Cranial magnetic resonance imaging in diagnosis of multiple sclerosis. PMID- 2896891 TI - Cocaine and HIV seropositivity. PMID- 2896893 TI - Empty sella syndrome and pituitary apoplexy. PMID- 2896894 TI - Obstetrics for medical students. PMID- 2896895 TI - Surgical training. PMID- 2896896 TI - UK medical research. PMID- 2896897 TI - Campylobacter pylori in patients with gastritis, peptic ulcer, and carcinoma of the stomach in Lanzhou, China. PMID- 2896898 TI - Stomach cancer cluster in Mexico. PMID- 2896900 TI - Why does placebo improve severe limb ischaemia? PMID- 2896899 TI - Thrombolytic therapy and percutaneous coronary angioplasty. PMID- 2896901 TI - Patient's choice between transcervical and transabdominal chorionic villus sampling. PMID- 2896902 TI - Pentamidine: which salt? PMID- 2896903 TI - Specific IgE antibodies to Bordetella pertussis after immunisation in infancy. PMID- 2896904 TI - Age prevalence of antibody to human herpesvirus 6. PMID- 2896905 TI - Isolation of human herpesvirus 6 from saliva. PMID- 2896906 TI - Human herpesvirus 6 and myalgic encephalomyelitis. PMID- 2896907 TI - Illegible prescriptions. PMID- 2896908 TI - Suicide verdict requires death within a year and a day. PMID- 2896909 TI - Identification of human herpesvirus-6 as a causal agent for exanthem subitum. AB - A virus was isolated from the peripheral blood lymphocytes of patients with exanthem subitum, cultured successfully in cord blood lymphocytes, and shown to be antigenically related to human herpesvirus-6 (HHV-6). Morphological features, as studied by thin-section electronmicroscopy, resembled those of herpes group viruses. Convalescent-phase serum samples, tested against the new viral antigen and HHV-6 antigen, showed seroconversion. The results strongly suggest that the newly isolated virus is identical or closely related to HHV-6 and the causal agent for exanthem subitum. PMID- 2896910 TI - Primary biliary cirrhosis: identification of two major M2 mitochondrial autoantigens. AB - Primary biliary cirrhosis (PBC) is characterised by the presence of antimitochondrial antibodies. The PBC-specific, immunoreactive, trypsin-sensitive antigens on the inner mitochondrial membrane (M2) have hitherto not been identified. A major 70 kD M2 autoantigen is the E2 component (lipoate acetyltransferase) of the pyruvate dehydrogenase enzyme complex located within mitochondria. This has been confirmed by immunoblotting of PBC patients' sera against purified E2 protein: sera from 38/40 (95%) patients with established clinical, biochemical, and histological features of PBC (18 stage II/III, 22 stage IV) reacted positively with E2; whilst no sera from 39 controls (27 non-PBC chronic liver disease, 12 healthy normal women) gave a positive response. Immunoblotting showed that a second subunit of the pyruvate dehydrogenase complex, a 50 kD polypeptide of unknown function (component X), is also an M2 autoantigen. Identification of these M2 mitochondrial antigens should facilitate the development of a specific serological test for PBC and the study of autoimmunising epitopes. PMID- 2896911 TI - Apolipoproteins (a), AI, and B and parental history in men with early onset ischaemic heart disease. AB - Middle-aged men who had had a myocardial infarction were compared with controls matched for social background, age, cigarette-smoking, blood pressure, and alcohol consumption. Serum cholesterol, triglycerides, very low density lipoprotein, low density lipoprotein, high density lipoprotein (HDL), HDL2 and HDL3 cholesterol, and serum apolipoproteins (apo) (a), AI, and B were measured. Discriminant analysis showed that the combination of these variables that best distinguished patients from controls was provided by apo AI and apo B and a knowledge of parental history of early cardiac death, the most discriminating single factor being apo B. No other variable contributed more than these. Apo (a), however, could be substituted for parental history, which had a major influence on the serum concentration of apo (a). Apo (a) concentration accounted for much of the familial predisposition to cardiac ischaemia. These findings may prove valuable in the clinical assessment of genetic susceptibility to myocardial infarction. They also support the hypothesis that serum apo (a) concentration is a genetic trait that predisposes to arterial thrombosis. Apo B emerged as the main lipoprotein determinant of coronary disease risk. PMID- 2896912 TI - Detection of drugs in the urine of body-packers. AB - The presence of opiates and benzoylecgonine, the major metabolite of cocaine, in the urine was detected by means of enzyme immunoassay in a series of 120 smugglers who had either ingested or inserted into their rectum cocaine or heroin packaged for transportation. There was a striking relation between the presence of drugs in the urine and swallowing of drug-filled bundles (cocaine 49 of 50 cases, heroin 9 of 10). The proportion of positive results was also high in cases of rectal insertion (cocaine 2 of 2, heroin 35 of 58). In 30 cases of cocaine packet ingestion, serial measurements showed that the accuracy of the test progressively decreased with respect to the detection of residual packets in the body. Drug detection in the urine of suspected body-packers seems to be a useful test, positive results justifying subsequent radiological investigations. PMID- 2896913 TI - Contribution of gut bacterial metabolism to human metabolic disease. AB - Metronidazole, an antibiotic with specific activity against anaerobic bacteria, was of clinical and biochemical benefit in two patients with methylmalonic aciduria. The virtual elimination of propionic acid from the stool suggested that propionic acid derived from faecal bacterial metabolism contributes substantially to methylmalonate production. These findings point to a novel avenue of treatment for these disorders of intermediary metabolism, and indicate the importance of microbial gut flora in normal human metabolism. PMID- 2896914 TI - Fish oil. PMID- 2896915 TI - Analgesia in children after day-case surgery. PMID- 2896916 TI - Enoximone. PMID- 2896917 TI - Milk--with care. PMID- 2896918 TI - Embryos and Parkinson's disease. PMID- 2896919 TI - Effect of intravenous nitrates on mortality in acute myocardial infarction: an overview of the randomised trials. AB - About 2000 patients have been randomised in ten trials of intravenous nitroglycerin or nitroprusside in acute myocardial infarction. Taken separately, the individual trials have all been too small to provide a reliable estimate of the effects of treatment on mortality, but collectively they provide strong evidence of benefit. In total there have been 136 nitrate and 193 control deaths, and an appropriate overview of the separate trial results indicated a "typical" reduction of 35% (SD 10) in the odds of death (2p less than 0.001, with 95% confidence limits of about one-sixth to one-half). Both nitroglycerin and nitroprusside reduced mortality, the reduction being non-significantly greater with nitroglycerin than with nitroprusside. The greatest reduction in mortality occurred during the first week or so of follow-up, with a non-significant further reduction after this early period. This suggests that the early benefit is not rapidly lost. PMID- 2896920 TI - Primary prevention of vascular disease by aspirin. PMID- 2896921 TI - Analysis of 1071 gift procedures--the case for a flexible approach to treatment. AB - An analysis of the outcome of first gamete intrafallopian transfers for 1071 women indicates that for those aged 40 years or more all the oocytes had to be transferred to obtain a 19.2% pregnancy rate. In this age-group pregnancy rate and multiple pregnancy rate were significantly lower than those for younger women. Success rate, but not multiple pregnancy rate, was significantly higher in the group of women from whom 11 or more oocytes were recovered and transferred after ovulation induction than when only 1-4 oocytes were recovered and transferred. The findings suggest that the number of oocytes transferred should depend on clinical circumstances. PMID- 2896922 TI - Pancreas transplantation for diabetes. PMID- 2896923 TI - Screening for inherited metabolic diseases in adults with neurological disease. PMID- 2896924 TI - Carotid endarterectomy trial: word of caution. PMID- 2896925 TI - Scrotal endoscopy in male infertility. PMID- 2896926 TI - Gonococcal disease as a cause of acute tropical polyarthritis. PMID- 2896927 TI - Nursing preterm infants. PMID- 2896928 TI - Which salt of erythromycin is most hepatotoxic? PMID- 2896929 TI - Treatment of tubal pregnancy by prostaglandins. PMID- 2896930 TI - Adenosine injection. PMID- 2896931 TI - Cost of preventing transfusion of hepatitis B virus in hyperendemic areas. PMID- 2896932 TI - Childhood sexual abuse and women's health. PMID- 2896933 TI - Erythropoietin, haemoglobin, and hypertensive crises. PMID- 2896934 TI - Solitary rectal ulcer. PMID- 2896935 TI - Cortical blindness. PMID- 2896936 TI - Rubella infection and reinfection distinguished by avidity of IgG. PMID- 2896937 TI - Biopterin and organ transplantation. PMID- 2896938 TI - IgA antigliadin antibodies in children with IgA mesangial glomerulonephritis. PMID- 2896939 TI - Chlamydial infection. PMID- 2896940 TI - Suicide, selection, and A-bomb survivors. PMID- 2896941 TI - AIDS, anal sex, and heterosexuals. PMID- 2896942 TI - HIV infection of rectal mucosa. PMID- 2896943 TI - Core curriculum in medicine. PMID- 2896944 TI - Doctors involved with torture. PMID- 2896945 TI - Last-minute ban on medical visit to South Africa. PMID- 2896946 TI - Routine urinalysis. PMID- 2896948 TI - Temazepam capsules. PMID- 2896947 TI - Whooping cough in Stuttgart. PMID- 2896949 TI - Teratogens and perinatal epidemiology. PMID- 2896950 TI - Thyroid papillary carcinoma in identical twins. PMID- 2896951 TI - Oral contraceptives and gallstones. PMID- 2896952 TI - Fatal hypokalaemia associated with ifosfamide/mesna chemotherapy. PMID- 2896953 TI - Allergic reactions to cuttlefish in deep-sea fishermen. PMID- 2896954 TI - A Talmudic hangover. PMID- 2896955 TI - Prognostic factors in Hodgkin's disease. PMID- 2896956 TI - AIDS policy. PMID- 2896957 TI - Comparison of two strategies for control of malaria within a primary health care programme in the Gambia. AB - Two drug strategies for the control of malaria in children aged 3-59 months have been compared in a rural area of The Gambia--treatment of presumptive episodes of clinical malaria with chloroquine by village health workers, and treatment combined with fortnightly chemoprophylaxis with 'Maloprim' (pyrimethamine/dapsone) which was also given by village health workers. Treatment alone did not have any significant effect on mortality or morbidity from malaria. In contrast, treatment and chemoprophylaxis reduced overall mortality in children aged 1-4 years, mortality from probable malaria, and episodes of fever associated with malaria parasitaemia. A high level of compliance with chemoprophylaxis was obtained and no harmful consequences of chemoprophylaxis were observed. PMID- 2896958 TI - T lymphocyte activation in acute severe asthma. AB - T lymphocyte subsets and lymphocyte activation markers in the peripheral blood were assessed in patients admitted to hospital with acute severe asthma (status asthmaticus). Measurements were made on admission, day 3, and day 7 (or on discharge from hospital if this was sooner). The results were compared with 3 control groups (mild asthma, chronic obstructive airways disease, and normal individuals). The percentages of CD4-positive and CD8-positive T lymphocytes, and the CD4/CD8 ratios, were similar in the patients with acute severe asthma and the control groups, and were within the normal range. In contrast, patients with acute severe asthma had significant increases, compared with control subjects, of three surface proteins associated with T lymphocyte activation: interleukin-2 receptor (IL-2R); class II histocompatibility antigen (HLA-DR); and "very late activation" antigen (VLA-1). The IL-2R-positive T lymphocytes were exclusively of the CD4 "helper-inducer" phenotype. The percentages of IL-2R-positive and HLA-DR positive (but not VLA-1-positive) lymphocytes tended to decrease as the patients were treated and clinically improved, although these values remained raised above control values for the observation period. Cell-mediated immunity may be causally related to the pathogenesis of acute severe asthma. PMID- 2896959 TI - Granulomatous hepatitis associated with cat scratch disease. AB - In three patients with cat scratch disease the liver was affected. All three had high fever (39 degrees C) for more than 3 weeks. Two of them had no peripheral adenopathy. Computed tomography of the abdomen revealed focal hepatic defects in two patients and periportal and periaortic adenopathy in the third. At laparotomy, there were nodules on the liver surfaces of all patients and histological examination revealed necrotising granulomata. The Warthin-Starry silver stain showed organisms consistent in appearance with the cat scratch bacillus in the liver and a periaortic lymph node of one patient, in the liver of the second patient, and in the axillary lymph node of the third. In all three patients the clinical findings and radiological abnormalities improved without specific therapy. A review of the surgical pathology files of Washington University revealed only two other cases of granulomatous hepatitis in children over a 6-year period. These findings indicate that cat scratch disease should now be included in the differential diagnosis of granulomatous hepatitis, at least in children. The absence of peripheral adenopathy in two of the three patients with granulomatous hepatitis suggests that the clinical spectrum of cat scratch disease may be broader than previously appreciated. PMID- 2896960 TI - A cellular basis for the primary long Q-T syndromes. AB - In several syndromes sudden death is associated with a long Q-T interval on the electrocardiogram. Current treatment is aimed at correcting a notional imbalance of cardiac sympathetic drive. Although this approach can be effective, the primary disorder may be a defect in the cellular mechanism that alters the length of the ventricular action potential, and hence the Q-T interval, in response to a change of heart rate. Such defects may be underdiagnosed because the long Q-T syndromes are defined simply in terms of a prolonged Q-T interval, without consideration of the fact that susceptibility to arrhythmias is likely to be due, not to a lengthened Q-T per se, but to an absence or alteration of the normal Q-T shortening in response to an increase of heart rate. People susceptible to R-on-T related arrhythmias could be identified by measurement of the dependence of the Q T interval on heart rate and how quickly the Q-T interval adapts to a change in rate. PMID- 2896961 TI - Apolipoprotein-B and atherogenesis. PMID- 2896962 TI - Penicillin-resistant pneumococci. PMID- 2896963 TI - Inactive ingredients in medicines. PMID- 2896964 TI - Hole for the mint. PMID- 2896965 TI - Benign asbestos pleural effusions. PMID- 2896966 TI - Is ultrasound really necessary for the diagnosis of hypertrophic pyloric stenosis? PMID- 2896967 TI - Recurrence of duodenal ulcer after medical treatment. AB - 562 patients whose duodenal ulcers had healed in a series of double-blind controlled trials of various medical treatments were enrolled in a long-term endoscopic follow-up. 436 were followed for up to four years or until relapse. Relapse rates did not differ between the groups treated with cimetidine, ranitidine, pirenzepine, or placebo. At six and twelve months but not subsequently, there was a significant advantage for tripotassium dicitrato bismuthate. Relapse rates were at all times higher in smokers than in non smokers. PMID- 2896968 TI - Upper gastrointestinal cancer in familial adenomatous polyposis. AB - Invasive upper gastrointestinal adenocarcinoma was found in 57 (4.5%) of 1255 patients with familial adenomatous polyposis, recorded in 10 registries. The most frequent sites were duodenum in 29, pancreatic ampulla in 10, and stomach in 7. These findings confirm an increased risk of upper gastrointestinal cancer in the polyposis patient, particularly distal to the pylorus, and support an adenoma carcinoma sequence. Regular surveillance of the upper gastrointestinal tract is essential in patients with familial adenomatous polyposis. PMID- 2896969 TI - The aetiology of spinal deformities. AB - There are two types of spinal deformity, lordosis and kyphosis, and they are mutually exclusive at the same site. Lordosis is rotationally unstable and buckles to the side with growth and spinal flexion, producing scoliosis and changes in transverse plane geometry as secondary phenomena. Kyphosis is a uniplanar deformity arising behind the axis of spinal column rotation and it does not buckle. Spinal balance in the sagittal plane is delicate and in the normal child during adolescence both idiopathic scoliosis and idiopathic kyphosis can easily develop. The development and progression of spinal deformities can be explained in biological and mechanical terms. Any condition in which the critical load to the spine is reduced will favour the production and progression of a spinal deformity. Neuromuscular factors in idiopathic scoliosis are additive and not causative. PMID- 2896970 TI - The physician's responsibility to the patient. PMID- 2896971 TI - Should patients who smoke be referred for coronary artery bypass grafting? PMID- 2896972 TI - Leukaemia in patients treated with growth hormone. PMID- 2896973 TI - Human milk fortification. PMID- 2896974 TI - Energy intake from birth to 2 years. PMID- 2896975 TI - Incidence of IgA nephropathy. PMID- 2896976 TI - Xamoterol in heart failure. PMID- 2896977 TI - Magnetic resonance imaging in myeloma. PMID- 2896978 TI - Deterioration of primary biliary cirrhosis during treatment with ursodeoxycholic acid. PMID- 2896979 TI - Transmission of HTLV-1. PMID- 2896981 TI - Limulus assay in prediction of septic shock. PMID- 2896980 TI - Pneumonia in childhood. PMID- 2896982 TI - Ultrasonic nebulised pentamidine for pneumocystis pneumonia. PMID- 2896983 TI - Comparison of Teknaf enteric agar and MacConkey/salmonella-shigella agar in evaluation of Shigella infection. PMID- 2896985 TI - Meningococcal rash. PMID- 2896984 TI - Pathogenic Entamoeba. PMID- 2896986 TI - Listeria in prepacked salads. PMID- 2896987 TI - Penicillin-insensitive Neisseria meningitidis. PMID- 2896988 TI - Tyramine in alcohol-free beer. PMID- 2896989 TI - Homozygosity mapping and Friedreich's ataxia. PMID- 2896990 TI - Waterborne non-A, non-B hepatitis. PMID- 2896991 TI - Unilateral facial pain in patients with lung cancer. PMID- 2896992 TI - Aortic aneurysm and deep venous thrombosis. PMID- 2896993 TI - Buspirone in treatment of agitated demented patient. PMID- 2896994 TI - Detention of schoolchildren in South Africa. PMID- 2896995 TI - Academic medicine in crisis. PMID- 2896996 TI - Water standards for fluoride. PMID- 2896997 TI - Toxocariasis in children. PMID- 2896998 TI - Time course of cerebral vasospasm after severe head injury. PMID- 2896999 TI - Increased bone pain after suspension of buserelin treatment in disseminated prostatic cancer. PMID- 2897000 TI - Lignocaine-prilocaine cream for lumbar puncture in children. PMID- 2897001 TI - Osteosarcoma. PMID- 2897002 TI - No obligation to resuscitate a non-viable infant. PMID- 2897004 TI - WHO and UNDP unite against AIDS. PMID- 2897003 TI - AIDS in the UK. PMID- 2897005 TI - Relative efficacy of various physical manoeuvres in the termination of junctional tachycardia. AB - The ability of four vagotonic physical manoeuvres to terminate paroxysmal junctional tachycardias was tested in 35 patients with inducible and sustained arrhythmia. Each manoeuvre was used up to three times in an attempt to terminate an induced tachycardia and was judged to be effective if it terminated two out of the three induced episodes. The Valsalva manoeuvre in the supine position was effective in 19 (54%), right carotid sinus massage in 6 (17%), left carotid sinus massage in 2 (5%), and the diving reflex in 6 (17%) cases. 4 of the 6 patients who responded to right carotid sinus massage and all patients who responded to the diving reflex also responded to the Valsalva manoeuvre. The Valsalva manoeuvre while standing was effective in 9 (20%) patients only. Patients in whom the manoeuvres terminated the tachycardias were significantly younger than those who did not respond (median age: 30 vs 45 years, p less than 0.01). Physical manoeuvres were much more successful in terminating atrioventricular re-entry tachycardias (19/24) than atrioventricular nodal re-entry tachycardias (3/11, p less than 0.01). Efficacy of the manoeuvres was related to their bradycardic effect in sinus rhythm. PMID- 2897006 TI - HLA haplotype A1 B8 DR3 as a risk factor for HIV-related disease. AB - Of 32 patients exposed to a single batch of factor VIII contaminated with human immunodeficiency virus (HIV), 18 became antibody positive. Serial T cell subset analyses over the succeeding four years have shown a progressive decline in circulating T4 cells in those 18 but no change in the 14 who remain seronegative. 2 of the seroconverters have died and a further 7 have symptoms attributable to HIV infection. In the group as a whole, the HLA haplotype A1 B8 DR3 was weakly associated with an increased risk of seroconversion on exposure to the virus while, in those who seroconverted, it was strongly associated with a rapid decline in T4 cells and development of HIV-related symptoms within four years of infection. PMID- 2897007 TI - Diagnosis of acute herpes simplex encephalitis by brain perfusion single photon emission computed tomography. AB - Brain perfusion was studied in 14 patients with acute encephalitis by use of 123I iodoamphetamine or 99mTc-hexamethylpropyleneamine oxime and single photon emission computed tomography (SPECT), the first examination being made 4-11 days after onset of encephalitis symptoms. All 6 patients with herpes simplex virus encephalitis (HSVE) had strongly increased accumulation of radiotracer in the affected temporal lobe; in the remaining 8 results were normal. At the time of the first SPECT conventional CT images were normal in all patients. The SPECT abnormality in HSVE gradually converted over 4-10 weeks from increased tracer accumulation to greatly subnormal accumulation. Brain perfusion SPECT may be helpful in the early diagnosis of HSVE. PMID- 2897008 TI - Treatment of late Lyme borreliosis--randomised comparison of ceftriaxone and penicillin. AB - 23 patients with clinically active late Lyme disease were randomly assigned to intravenous treatment with either penicillin or ceftriaxone. Of the 10 treated with penicillin, 5 were judged treatment failures; of the 13 who received ceftriaxone, only 1 did not respond. An additional 31 patients were subsequently treated with ceftriaxone 4 g/day (n = 17) or 2 g/day (n = 14); success rates in both groups were comparable to those in the cohort randomised to ceftriaxone. Patients unresponsive to ceftriaxone were more likely to have received corticosteroid treatment. PMID- 2897009 TI - Granulocyte-macrophage colony stimulating factor expands the circulating haemopoietic progenitor cell compartment in man. AB - The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on bone marrow and peripheral-blood progenitor cells was investigated in a three-phase study in 13 patients with sarcoma. In the first phase patients were given GM-CSF alone. In phase II, which started a week after completion of phase I, patients received a course of cytotoxic chemotherapy, then a course of GM-CSF. Phase III consisted only of cytotoxic chemotherapy. GM-CSF (phase I) alone produced an 18 fold increase in peripheral blood granulocyte-macrophage colony-forming units (CFU-GM) and an 8-fold increase in erythroid burst-forming units (BFU-E) in the peripheral blood. GM-CSF had no effect on bone-marrow CFU-GM and BFU-E in the group as a whole. Three patients were investigated after phases II and III. GM CSF increased the absolute number of peripheral blood CFU-GM by approximately 60 fold compared with the pretreatment baseline. These effects of GM-CSF may be of clinical importance with regard to facilitating the harvest of peripheral blood progenitor cells for autotransplantation. PMID- 2897011 TI - All change at the WHO. PMID- 2897010 TI - Automatic defibrillators. PMID- 2897012 TI - Renal involvement in myeloma. PMID- 2897013 TI - Factor-VIII-related antigen and vasculitis. PMID- 2897014 TI - Cranial decompression. PMID- 2897015 TI - Bleeding in renal failure. PMID- 2897016 TI - A rational approach for assessing the hypothalamo-pituitary-adrenal axis. AB - In 70 paired insulin tolerance tests (ITTs) and short 'Synacthen' tests (SSTs), both of which have been advocated for assessment of the hypothalamo-pituitary adrenal (HPA) axis, there were 51 passes on both tests, 9 failures on both, and 10 discrepant results (9 failures on the SST, 1 failure on the ITT). There was a close correlation between the maximum cortisol value achieved in the two tests. A survey of British endocrinologists showed that only 24% used the SST to assess the HPA axis. It is suggested that the SST should be used for the initial assessment of the HPA axis and the ITT reserved for patients who fail the SST, those on corticosteroid therapy, and those who have had an acute pituitary insult within 14 days. PMID- 2897017 TI - A free market in health care. PMID- 2897018 TI - Providing health care in war-torn rural Afghanistan. PMID- 2897019 TI - New challenges for the World Health Organisation. PMID- 2897020 TI - Tamoxifen and breast cancer in the elderly. PMID- 2897021 TI - Delayed assessment of mammographic abnormalities. PMID- 2897022 TI - Ceruletide to treat neonatal cholestasis. PMID- 2897023 TI - Hazards of oral charcoal. PMID- 2897024 TI - High-level gentamicin resistance in Streptococcus faecalis. PMID- 2897025 TI - Evolution towards AIDS in HIV-infected individuals. PMID- 2897026 TI - Donor screening for HIV: how many false negatives? PMID- 2897027 TI - Fatal acute HIV infection with aplastic anaemia, transmitted by liver graft. PMID- 2897028 TI - Heatstroke and army training. PMID- 2897029 TI - Red-cell size analysis in investigation of haematuria. PMID- 2897030 TI - Tropical and epidemic spastic paraparesis are different. PMID- 2897032 TI - Contact allergy to self-adhesive dressings. PMID- 2897031 TI - Cyclosporin metabolites and central-nervous-system toxicity. PMID- 2897033 TI - Yersinia and haemolytic uraemic syndrome. PMID- 2897034 TI - What causes oedema? PMID- 2897035 TI - Angina in general practice. PMID- 2897036 TI - Anorexia nervosa and the heart. PMID- 2897038 TI - Hepatitis B vaccination in newborn babies. PMID- 2897037 TI - Streptokinase plus beta-blockade after myocardial infarction. PMID- 2897039 TI - Growth during early teenage pregnancy. PMID- 2897041 TI - Classical versus lower segment caesarean section for very-low-birthweight infants. PMID- 2897040 TI - Breast not necessarily best. PMID- 2897042 TI - Deaths from conditions amenable to medical intervention: are they really avoidable? PMID- 2897043 TI - South Africa's children. PMID- 2897044 TI - Asking for organs. PMID- 2897045 TI - Medical staffing in the NHS. PMID- 2897046 TI - Ciprofloxacin and malaria. PMID- 2897047 TI - Carcinogenic nitrosamines in oral snuff. PMID- 2897048 TI - Hypoglycaemia induced by cibenzoline. PMID- 2897049 TI - Food allergy and dyspepsia. PMID- 2897050 TI - Xenogeneic antibodies, idiotypes, and atopic disease. PMID- 2897051 TI - H2 antagonist non-responders. PMID- 2897052 TI - Bacterial diarrhoea and treatment. PMID- 2897053 TI - Simplifying personal injury litigation. PMID- 2897054 TI - GABA transaminase inhibitors enhance the release of endogenous GABA but decrease the release of beta-alanine evoked by electrical stimulation of slices of the rat medulla oblongata. AB - Slices of the rat medulla oblongata were superfused and electrically stimulated. The amount of endogenous GABA, beta-alanine and glutamate release from the slices was determined by high performance liquid chromatography with fluorometric detection. Inhibitors of GABA-transaminase (GABA-T), aminooxyacetic acid (10(-5) M), gamma-acetylenic GABA (10(-4) and 10(-3) M) and gabaculine (10(-5) M), enhanced the stimulus-evoked release of GABA and reduced that of beta-alanine, while no change was observed in the release of glutamate. These changes in amino acid release from the slices were accompanied by an increase in the content of GABA and a decrease in that of beta-alanine. The stimulus-evoked release of these amino acids was abolished by Ca2+-deprivation, in either the presence or absence of GABA-T inhibitors. These results suggest a modulatory role of GABA-T for synaptically releasable GABA and involvement of this enzyme in the synthesis of releasable beta-alanine. PMID- 2897055 TI - Levallorphan and dynorphin improve motor dysfunction in Mongolian gerbils with unilateral carotid occlusion: the first application of the inclined plane method in the experimental cerebral ischemia. AB - Levallorphan and dynorphin were effective on the motor dysfunction in the gerbil model of unilateral cerebral ischemia. The effect of opioids, levallorphan (mixed agonist-antagonist), dynorphin (kappa-receptor agonist) and naloxone (mu-receptor antagonist), on neurological impairment was evaluated using the unilateral cerebral ischemia model of gerbil. Motor function was evaluated quantitatively by using the inclined plane method. Both levallorphan-treated group and dynorphin treated group showed a significant improvement of the motor dysfunction compared with saline-control group. On the other hand, naloxone-treated group did not differ from saline-control group. The beneficial effect of these opioids on motor dysfunction might be mediated by the kappa-opioid receptor. This study also showed the potential usefulness of the inclined plane method for the investigation on the cerebral ischemia. PMID- 2897056 TI - Cerebral neocortex modulation of immune functions. PMID- 2897057 TI - Effect of vitamin D on gastrin and gastric somatostatin secretion from the isolated perfused rat stomach. AB - We have studied the role of vitamin D in the regulation of gastrin and gastric somatostatin secretion from the isolated perfused rat stomach. In Ca-deficient vitamin D-deficient rats (Ca(-)D(-) group), the basal and bombesin-stimulated gastrin and gastric somatostatin release (basal IRGa, basal IRS, sigma delta IRGa, and sigma delta IRS) all were significantly lower than in Ca-replete vitamin D-replete rats (Ca(+)D(+) group), and also lower than in Ca-replete vitamin D-deficient rats (Ca(+)D(-) group) except for the basal IRGa. In the Ca(+)D(-) group, the basal IRGa and IRS, and sigma delta IRS were not significantly lower than in the Ca(+)D(+) group. Although there was no significant impairment in basal IRGa, sigma delta IRGa in the Ca(+)D(-) group was significantly lower than in the Ca(+)D(+) control group. Thus, the gastrin and gastric somatostatin secretion from the Ca-deficient vitamin D-deficient rats were impaired. In addition, the impaired gastrin and gastric somatostatin secretions seem to be caused not only by a decrease in serum Ca but also by the reduced effect of the vitamin D on the G and gastric D cells. PMID- 2897058 TI - Determination of amino acids in different regions of the rat brain. Application to the acute effects of tetrahydrocannabinol (THC) and trimethyltin (TMT). AB - A modified HPLC method is described for the determination of amino acids [aspartic acid, glutamic acid, glutamine, glycine, taurine, and gamma aminobutyric acid (GABA)] in brain tissue utilizing precolumn derivatization with o-phthalaldehyde (OPA)-tert-butyl-thiol and electrochemical detection. A simple extraction procedure was employed and DL-homoserine used as internal standard. A neurotoxin previously shown to affect brain amino acids (trimethyltin, TMT) and a psychoactive compound hypothesized to act on these neurochemicals (delta-9 tetrahydrocannabinol, THC) were administered to adult male rats and amino acids were measured. Results revealed a gradient of distribution of most amino acids, with lowest levels posteriorly in the brain stem and increasing to the highest values in anterior cortical regions. TMT increased glutamine significantly in all brain regions examined, but increased glycine and decreased taurine only in the frontal cortex and hippocampus. No significant changes in any amino acid were found in hippocampus after THC treatment. The results establish the validity and usefulness of this HPLC method for detecting neurotoxicity-related changes in brain amino acid metabolism. PMID- 2897059 TI - Synthesis of platelet activating factor by cholinephosphotransferase in developing fetal rabbit lung. AB - Developing fetal lung is a possible source of the platelet activating factor (PAF, 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) present in amniotic fluid of women in labor. We have assayed the microsomal activities of a specific enzyme for the de novo synthesis of PAF in developing fetal and neonatal rabbit lung, 1 alkyl-2-acetyl-glycerol-dependent dithiothreitol-insensitive cholinephosphotransferase. The specific activity of this enzyme increased from 0.92 to 3.60 nmol X min-1 X mg-1 protein between day 21 and day 31 of gestation. In constrast, during this same period the activity of the PAF-biosynthetic cholinephosphotransferase in developing rabbit kidney did not change significantly. The specific activity of the diacyl-glycerol-dependent, dithiothreitol-sensitive cholinephosphotransferase that catalyzes the final step in phosphatidylcholine biosynthesis was not altered during late gestation in either fetal lung or kidney. Previously, increased amounts of pulmonary PAF had been found during the latter stages of gestation (Hoffman, Truong and Johnston (1986) Biochim. Biophys. Acta 879, 88-96) and may be attributed to increased activity of the PAF biosynthetic enzymes found in this investigation. This elevated level of PAF in fetal lung may serve to facilitate breakdown of glycogen that provides, in part, the carbon and energy source for surfactant biosynthesis. In addition, PAF may be secreted in association with surfactant into amniotic fluid in which it may interact with amnion tissue and subsequently participate in the events associated with the initiation of parturition. PMID- 2897060 TI - Methods for computing the standard errors of branching points in an evolutionary tree and their application to molecular data from humans and apes. AB - Statistical methods for computing the standard errors of the branching points of an evolutionary tree are developed. These methods are for the unweighted pair group method-determined (UPGMA) trees reconstructed from molecular data such as amino acid sequences, nucleotide sequences, restriction-sites data, and electrophoretic distances. They were applied to data for the human, chimpanzee, gorilla, orangutan, and gibbon species. Among the four different sets of data used, DNA sequences for an 895-nucleotide segment of mitochondrial DNA (Brown et al. 1982) gave the most reliable tree, whereas electrophoretic data (Bruce and Ayala 1979) gave the least reliable one. The DNA sequence data suggested that the chimpanzee is the closest and that the gorilla is the next closest to the human species. The orangutan and gibbon are more distantly related to man than is the gorilla. This topology of the tree is in agreement with that for the tree obtained from chromosomal studies and DNA-hybridization experiments. However, the difference between the branching point for the human and the chimpanzee species and that for the gorilla species and the human-chimpanzee group is not statistically significant. In addition to this analysis, various factors that affect the accuracy of an estimated tree are discussed. PMID- 2897061 TI - Biochemical pathways in prokaryotes can be traced backward through evolutionary time. AB - For the first time, a credible prokaryotic phylogenetic tree is being assembled by Woese and others using quantitative sequence analysis of oligonucleotides in the highly conservative rRNA. This provides an evolutionary scale against which the evolutionary steps that led to the arrangement and regulation of contemporary biochemical pathways can be measured. This paper presents an emerging evolutionary picture of aromatic amino acid biosynthesis within a large superfamily assemblage of prokaryotes that is sufficiently developed to illustrate a new perspective that will be applicable to many other biochemical pathways. PMID- 2897062 TI - Molecular evidence for the rapid propagation of mouse t haplotypes from a single, recent, ancestral chromosome. AB - Mouse t haplotypes are variant forms of chromosome 17 that exist at high frequencies in worldwide populations of two species of commensal mice. To determine both the relationship of t haplotypes to each other and the species within which they exist, 35 representative t haplotypes were analyzed by means of 10 independent molecular probes, including five DNA clones and five polypeptide spots identified by means of two-dimensional gel electrophoresis. All of the tested haplotypes were found to share restriction fragments and polypeptide spots that are absent in mice carrying wild-type forms of chromosome 17. This observation provides the first direct evidence that all of the known t haplotypes are descendents of a single ancestral chromosome. The absence of variation among t haplotypes could mean that this ancestral chromosome existed relatively recently, in which case it would be necessary to postulate introgressions of t haplotypes across species lines to explain their presence in both Mus domesticus and M. musculus. Alternatively, it is possible that the ancestral chromosome existed prior to the split between M. domesticus and M. musculus and that, by chance, our probes fail to detect polymorphisms that exist among the t haplotypes. A further result of our analysis is the characterization of a partial t haplotype in a wild population of Israeli mice. PMID- 2897063 TI - Phylogenetic distribution in the genus Mus of t-complex-specific DNA and protein markers: inferences on the origin of t-haplotypes. AB - We have examined the phylogenetic distribution of two t-specific markers among representatives of various taxa belonging to the genus Mus. The centromeric TCP 1a marker (a testicular protein variant specific for all t-haplotypes so far studied) has also been apparently detected in several non-t representatives of the Mus IVA, Mus IVB, and probably M. cervicolor species. By contrast, a t specific restriction-fragment-length polymorphism allele (RFLP) of the telomeric alpha-globin pseudogene DNA marker alpha-psi-4 was found only in animals belonging to the M. musculus-complex species either bearing genuine t-haplotypes or, like the M. m. bactrianus specimen studied here, likely to do so. This t specific alpha-psi-4 RFLP allele was found to be as divergent from the RFLP alleles of the latter, non-t, taxonomical groups as it is from Mus 4A, Mus 4B, or M. spretus ones. These results suggest the presence of t-haplotypes and of t specific markers in populations other than those belonging to the M. m. domesticus and M. m. musculus subspecies, implying a possible origin for t haplotypes prior to the radiation of the most recent offshoot of the Mus genus (i.e., the spretus/domesticus divergence), some 1-3 Myr ago. PMID- 2897064 TI - Nucleotide sequence, regulation and functional analysis of the papC gene required for cell surface localization of Pap pili of uropathogenic Escherichia coli. AB - The papC gene of uropathogenic Escherichia coli is required for the formation of digalactoside-binding Pap pili. papC forms part of an operon wherein the regulatory gene papB, the major pilin gene papA, a minor pilin-like gene papH, and papC are co-transcribed. Furthermore, the extent of PapC synthesis was found to affect the number of pili expressed on the cell surface. The DNA sequence of the papC gene is presented and its deduced amino acid sequence is compared to that of the FaeD protein encoded by the K88 pili gene cluster. The PapC protein was localized to the E. coli outer membrane where it may form a trans-membrane channel through which pilin subunits are surface localized. PMID- 2897065 TI - Cloning and nucleotide sequence analysis of the serotype 2 fimbrial subunit gene of Bordetella pertussis. AB - An oligonucleotide probe complementary to the beginning of the gene encoding the serotype 2(ST2) fimbrial subunit of Bordetella pertussis was synthesized and a cloned DNA fragment hybridizing with the probe identified and sequenced. Several lines of evidence indicate that an open reading frame with coding information for a polypeptide of 207 amino acids, including a 26-amino-acid signal sequence, is the ST2 gene. The protein deduced from the nucleotide sequence shows good agreement with the NH2-terminal amino acid sequence, amino acid composition and molecular weight of the purified fimbrial subunit. In addition, the proposed ST2 subunit is shown to have homology with other fimbrial subunits. PMID- 2897066 TI - Primary structure and subcellular localization of two fimbrial subunit-like proteins involved in the biosynthesis of K99 fibrillae. AB - Analysis of the nucleotide sequence of the distal part of the fan gene cluster encoding the proteins involved in the biosynthesis of the fibrillar adhesin, K99, revealed the presence of two structural genes, fanG and fanH. The amino acid sequence of the gene products (FanG and FanH) showed significant homology to the amino acid sequence of the fibrillar subunit protein (FanC). Introduction of a site-specific frameshift mutation in fanG or fanH resulted in a simultaneous decrease in fibrillae production and adhesive capacity. Analysis of subcellular fractions showed that, in contrast to the K99 fibrillar subunit (FanC), both the FanH and the FanG protein were loosely associated with the outer membrane, possibly on the periplasmic side, but were not components of the fimbriae themselves. PMID- 2897067 TI - The calmodulin-sensitive adenylate cyclase of Bordetella pertussis: cloning and expression in Escherichia coli. AB - The adenylate cyclase toxin of the prokaryote Bordetella pertussis is stimulated by the eukaryotic regulatory protein, calmodulin. A general strategy, using the adenylate-cyclase-calmodulin interaction as a tool, has permitted cloning and expression of the toxin in Escherichia coli in the absence of any B. pertussis trans-activating factor. We show that the protein is synthesized in a large precursor form composed of 1706 amino acids. The calmodulin-stimulated catalytic activity resides in the amino-terminal 450 amino acids of the adenylate cyclase. The enzyme expressed in E. coli is recognized in Western blots by antibodies directed against purified B. pertussis adenylate cyclase, and its activity is inhibited by these antibodies. PMID- 2897068 TI - Biogenesis of F7(1) and F7(2) fimbriae of uropathogenic Escherichia coli: influence of the FsoF and FstFG proteins and localization of the Fso/FstE protein. AB - The F7(1) and F7(2) P-fimbriae of Escherichia coli are encoded by the fso (F seven one) and fst (F seven two) gene clusters, respectively (Van Die et al., 1984; 1985). With the immunocytochemical gold-labelling technique it was demonstrated that both the FsoE and FstE proteins are non-adhesive minor fimbrial subunits located at the tip of the fimbrial structure. The FsoF and FstFG proteins play an important role in the initiation of polymerization of the minor and major subunits into the fimbrial structure. PMID- 2897069 TI - Somatostatin infusion inhibits the stimulatory effect of testosterone on endosteal bone formation in the mouse. AB - To investigate whether the effects of testosterone (T) on endosteal bone metabolism may be mediated by growth hormone (GH), intact male mice were infused for ten days with T (5 or 15 mg/kg/d) alone, or combined either with native somatostatin (SRIF) (220 micrograms/kg/d) or with the long-acting somatostatin analog SMS 201-995. Testosterone infusion induced a dose-dependent increase in histomorphometric parameters of bone formation, causing a 25% increase in osteoblastic and osteoid surface and 10% to 12% stimulation of the matrix and mineral appositional rates. Stimulation of bone formation rate was associated with a 2- to 3-fold increase in the incidence of serum GH peaks of high amplitude. SRIF (220 micrograms/kg/d) and SMS at low dose (4.32 micrograms/kg/d) decreased parameters of bone formation by 20% to 25%. At a higher dosage (13 micrograms/kg/d), which mildly decreased serum glucose and longitudinal bone growth, SMS further reduced bone formation rate. Infusion of SRIF with T (5 mg/kg/d) blunted the stimulatory effect of T. Similarly, infusion of a high dose of SMS (13 micrograms/kg/d), together with T (15 mg/kg/d), abolished the effect of T (15 mg/kg/d) without altering serum glucose or mineral levels. The effect of SRIF on testosterone-induced (5 mg/kg/d) bone formation was associated with inhibition of T-induced high-amplitude GH peaks. The results indicate that T stimulates the osteoblastic bone formation in association with increased GH secretion, whereas SRIF and the analog SMS produce inhibitory effects. PMID- 2897070 TI - Effect of beta-blockade and subsequent triiodothyronine administration on human leucocyte Na-K ATPase. AB - We have investigated the effect of beta-blockade and beta-blockade + triiodothyronine (T3) administration on 86Rb (K) influx and [3H]-ouabain binding by human leucocytes and on plasma potassium concentrations. beta-blockade with nadolol (40 mg daily) for five days resulted in a significant decrease in 86Rb influx and [3H]-ouabain binding, as well as an increase in plasma potassium concentration. T3 administration thereafter caused a fall in plasma concentration and an increase in 86Rb influx. There was a tendency toward restoration of [3H] ouabain binding to normal. The fact that beta-blockade inhibits 86Rb (K) influx and increases plasma potassium concentration implies that endogenous adrenaline exerts a tonic stimulatory effect upon 86Rb (K) influx and a suppressive effect on plasma potassium concentrations in vivo. T3 administration induces an increase in 86Rb (K) influx and a fall in plasma potassium concentrations. This suggests that either the effect of T3 is independent of beta-adrenoceptors or that the known increase in beta-adrenoceptor population secondary to T3 administration increases sensitivity to circulating adrenaline in spite of beta-blocker administration. PMID- 2897071 TI - RNA processing and multiple transcription initiation sites result in transcript size heterogeneity in maize mitochondria. AB - Variation in the length of the 5' non-coding region of mitochondrial gene transcripts could result from multiple transcription initiation sites or post transcriptional processing events. To distinguish between these possibilities, we have utilized the in vitro capping reaction catalyzed by guanylyl transferase to specifically label the 5' end of primary, unprocessed transcripts. Hybridization of in vitro capped mtRNA to immobilized DNA from the 5' flanking regions of 26 S, 18 S and 5 S rRNA genes and two protein-coding genes, ATP synthase subunit 9 (atp9) and apocytochrome b (cob), identified regions where transcription initiates. Single-strand specific RNase treatment of in vitro capped RNA hybridized to immobilized DNA containing the 5' flanking sequences from cob and atp9 suggests that these genes have multiple transcription initiation sites. Direct mapping of transcription initiation sites for the rRNA genes indicated that single major transcription initiation sites exist at approximately 180 and 230 nucleotides upstream from the mature 26 S and 18 + 5 S rRNA genes, respectively. Labeling of processed transcripts bearing a 5' hydroxyl moiety with T4 polynucleotide kinase and subsequent hybridization to the rRNA genes indicated that the mature forms of the rRNA are processed. PMID- 2897073 TI - Report on the Sixth World Conference on Smoking and Health. PMID- 2897072 TI - Energy state of bovine cerebral microvessels: comparison of isolation methods. AB - Isolation procedures employed by various laboratories to obtain cerebral microvessels generally utilize meshes to sieve and collect the microvessels from homogenized brain. This is followed in some cases by further purification using density gradients of Percoll or sucrose, or albumin flotation. We have evaluated microvessels prepared by these methods in terms of ATP content and ATP/ADP ratio, which reflect the cellular energy state, and enrichment of the marker enzymes, alkaline phosphatase and gamma-glutamyltransferase. Albumin flotation generally increased the enrichment of marker enzymes; however, preparations using albumin flotation or a Percoll gradient exhibited considerable variability in ATP content and ATP/ADP ratio with the mean ATP/ADP ratio significantly lower than that observed in microvessels isolated by sieving through meshes. More uniformly high values for both ATP (approximately 1.6 nmole ATP/mg protein) and the ATP/ADP ratio (approximately 2.3) were obtained with meshes alone. Use of a sucrose gradient consistently resulted in preparations with a much lower ATP content and ATP/ADP ratio, compared with preparations obtained with the other methods. Values using the other methods were higher than those previously reported, yet were still lower than the ATP content of about 23 and ATP/ADP ratios of 18 and 7 we found in cultured microvascular endothelium and pericyte, respectively. These low values were not improved by supplying additional fuel to the microvessels during isolation, suggesting they were not the result of fuel deprivations during isolation. Despite the probable damage incurred during isolation, microvessel preparations are a useful in vitro model in which fuel metabolism appears to reflect the prior hormonal/nutritional state of donor animals. However, our data indicate the advisability of measurements of ATP content and ATP/ADP ratio for quality control of preparations used for metabolic studies, especially after Percoll density gradient or albumin flotation steps. PMID- 2897075 TI - Box-jellyfish envenomation. PMID- 2897074 TI - Fatal envenomation by Chironex fleckeri, the north Australian box jellyfish: the continuing search for lethal mechanisms. AB - A child with severe envenomation by Chironex fleckeri presented in cardiac arrest at a hospital between 15 and 20 min after the sting was sustained. Resuscitation was not successful. Objective confirmation of C. fleckeri as the cause of death is described. Four metres of tentacle contact in this case represents the smallest-measured fatal C. fleckeri sting that has been recorded so far. The mechanism of this death was toxic and not allergic. The available clinical information suggests direct myocardial interference, but does not exclude a respiratory hypoxic element. A more widespread venom-induced functional disruption of the cell membrane is postulated, with a resultant dysfunction in several vital organ systems that were acting in concert. Early, vigorous and sustained resuscitation that is performed as a first-aid measure offers the best hope of prehospital survival after a massive C. fleckeri sting, which is the most explosive envenomation process that is presently known to humans. In-hospital resuscitation from unresponsive circulatory arrest should now involve intravenously-administered verapamil (or its equivalent) and additional box jellyfish antivenom, while the patient is being monitored. PMID- 2897076 TI - [Culicidae fauna of the Ubsu-Nur basin]. PMID- 2897077 TI - [Clinical, etiologic, diagnostic and differential diagnostic aspects of Churg Strauss syndrome]. PMID- 2897078 TI - [Extensive lung involvement in periarteritis nodosa]. PMID- 2897079 TI - Tumor promoter and epidermal growth factor stimulate phosphorylation of the c erbB-2 gene product in MKN-7 human adenocarcinoma cells. AB - Treatment of human adenocarcinoma MKN-7 cells with epidermal growth factor (EGF) or phorbol tetradecanoate acetate (TPA) stimulated phosphorylation of the c-erbB 2 gene product. EGF induced a rapid increase in phosphotyrosine followed by relatively gradual increases in phosphoserine and phosphothreonine. On the other hand, the TPA-induced increase in phosphorylations occurred exclusively on serine and threonine residues. Tryptic phosphopeptide mapping analysis suggested that treatments with EGF and TPA induced phosphorylation of many common sites in the c erbB-2 gene product. However, in contrast to TPA, EGF increased the phosphorylation of the c-erbB-2 protein in cells whose protein kinase C had been down-regulated by long-term pretreatment with TPA, suggesting that EGF and TPA induce phosphorylation by different mechanisms. Since the c-erbB-2 gene product did not show detectable EGF-binding activity, phosphorylation of tyrosine of the c-erbB-2 gene product might be catalyzed directly by the EGF receptor kinase that was activated by EGF. PMID- 2897080 TI - Facilitation of a dendritic calcium conductance by 5-hydroxytryptamine in the substantia nigra. AB - Within the substantia nigra, the dendrites of dopaminergic neurons that project to the striatum appear to play an active and nonclassical role in the physiology of the neuron in that they release transmitter and protein, but little is known of the factors controlling release of substances from these dendrites. In this study, we show that 5-hydroxytryptamine, which is contained in afferent fibres to the substantia nigra, is present in terminals making direct synaptic contact with dopaminergic neurons and also that it has a site-dependent, receptor-mediated, facilitatory effect on a specific dendritic calcium-dependent potential in nigrostriatal neurons in vitro. The ionic and spatial features of this response, which is insensitive to blockade by three different K+-channel antagonists, could correspond to those underlying the dendritic release of dopamine. PMID- 2897081 TI - Complete structure of the glycosyl phosphatidylinositol membrane anchor of rat brain Thy-1 glycoprotein. AB - Glycosyl-phosphatidylinositol (GPI) anchors have recently been identified as alternatives to hydrophobic amino acid sequences for the attachment of a variety of eukaryotic cell surface molecules to the lipid bilayer. In single cell eukaryotes the GPI group appears to be the predominant form of membrane attachment, and in vertebrates a substantial minority of molecules have this anchor including cell surface hydrolytic enzymes, antigens and cell adhesion molecules. Analysis of different GPI anchors suggests they share common structural features including linkage to the COOH group of the terminal amino acid via ethanolamine phosphate, the presence of phosphatidylinositol lipid and a glycan between the bridging ethanolamine phosphate and the lipid. In the case of the Trypanosoma brucie variant surface glycoprotein (VSG) the full structure of the GPI anchor has been determined and this provides a prototype for comparison with other molecules. We now report the structure of the GPI anchor of rat brain Thy-1 glycoprotein. It has an identical backbone to the VSG anchor but shows significant differences in side chain moieties. PMID- 2897082 TI - Pharmacological characterization of alpha-adrenoceptors involved in nictitating membrane and pupillary responses to sympathetic nerve stimulation in cats. AB - Electrical stimulation of the preganglionic cervical sympathetic nerve produced frequency-related contraction of the nictitating membrane (NM) and dilation of the pupil in anesthetized cats. Observations of the effects of alpha-adrenoceptor blockade on these effectors were made simultaneously from the same preparations. All of the alpha 1-adrenoceptor antagonists tested produced a dose-related blockade of the NM with the relative potencies being prazosin greater than WB 4101 greater than phentolamine greater than phenoxybenzamine. In contrast, the iris dilator response was blocked by WB-4101 and phenoxybenzamine but was almost totally refractory to antagonism by doses of prazosin and phentolamine that reduced the evoked NM responses by more than 75% in these same preparations. Neither alpha 2-adrenoceptor (yohimbine or rauwolscine) nor beta-adrenoceptor (propranolol) antagonism produced significant inhibition of the activation of either organ. These results suggest that: 1) neural activation of the nictitating membrane is solely due to stimulation of alpha 1-adrenoceptors; 2) neither beta- nor alpha 2-adrenoceptors contribute significantly to nerve activation of either the nictitating membrane or iris dilator muscle in vivo; 3) the alpha adrenoceptors on the dilator muscle that are activated neurally can not be classified pharmacologically as either alpha 1 or alpha 2 receptors. PMID- 2897083 TI - Inhibition of a peripheral sympathetic-cholinergic system by presynaptic alpha 2 adrenoceptors. AB - Intravenous administration of catecholamines produced dose-related inhibition of electrodermal responses (EDRs) evoked by electrical stimulation of the post ganglionic sciatic nerve in anaesthetized rats, with relative potencies being (-) adrenaline greater than (+/-)-adrenaline greater than (-)-noradrenaline = (+) adrenaline. The suppression of EDRs by (+/-)-adrenaline and (-)-noradrenaline was blocked by pretreatment with yohimbine (0.75 mg/kg i.v.) but not by prazosin (0.3 mg/kg i.v.). The selective alpha 2-adrenoceptor agonist B-HT 920 also inhibited neurally evoked skin potential responses. This effect of B-HT 920 was antagonized by the selective alpha 2-adrenoceptor antagonist idazoxan (0.1 mg/kg i.v.) but was insensitive to prazosin. Idazoxan was more potent than yohimbine in blocking (+/-)-adrenaline-induced suppression of EDRs. Methacholine administered into the femoral artery evoked EDRs by an atropine-sensitive mechanism. Methacholine induced EDRs were not suppressed by intravenous administration of (-)-adrenaline (1 microgram/kg or 3 micrograms/kg) whereas EDRs evoked by the sciatic nerve stimulation on the other hindpaw were inhibited. Increase in the endogenous catecholamines by asphyxia strongly inhibited EDRs by a mechanism which was also sensitive to yohimbine but not to prazosin. These results suggest that peripheral presynaptic alpha 2-adrenergic mechanisms are involved in inhibition of transmitter release in this sympathetic-cholinergic system. PMID- 2897084 TI - Influence of protein kinase C-stimulation by a phorbol ester on neurotransmitter release at frog end-plates. AB - 1. The effect of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) on the stimulation-evoked neurotransmitter release has been investigated by measuring the quantal content (m) of end-plate potentials at frog neuromuscular junctions (Rana temporaria, M. sartorius). 2. After addition of TPA (0.1 up to 1 mumol/l) to the Ringer solution the m-values increased in a concentration dependent manner up to more than 3 times the control values. 3. Inhibition of the activity of the protein kinase C through the inhibitor 1-(5 isoquinolinylsulfonyl)-2-methylpiperazine (H-7) blocked this effect of TPA. 4. The TPA effect was much more conspicuous when the m-value was reduced by raising the extracellular Mg2+ concentration. Between the control m-values and the n-fold increase in the m-value enhanced by TPA a hyperbolic relation was observed. 5. It is concluded that protein kinase C stimulation affects predominantly the spontaneous release of neurotransmitter at the frog neuromuscular junction and only very poorly the stimulation-evoked one. PMID- 2897085 TI - Muscarinic receptor interaction with full and partial beta-adrenoceptor agonists in the rat colon strip. AB - beta-Adrenoceptor agonists inhibit contractile activity in isolated colon strips. In order to demonstrate that beta-adrenoceptors are located at different functional levels within the colon wall, increasing concentrations of muscarinic agonists were used to interact functionally with the beta-adrenoceptor-mediated inhibition of spontaneous colon activity. The effects of the full agonists isoprenaline and terbutaline and of the partial agonist prenalterol were functionally antagonized by carbachol (0.03 and 0.3 mumol/l) and bethanechol (1.3 and 30 mumol/l). This functional antagonism was parallelled by an increase in baseline tension and spontaneous contractile activity of the isolated colon strip. At lower concentrations of carbachol (0.003 and 0.01 mumol/l) or bethanechol (0.03 and 0.3 mumol/l) no effect on the contractile status of the smooth muscle or on the pD2-values of the full agonists was seen. However, at these lower concentrations of muscarinic agonists a marked decrease in the maximal inhibitory response to the partial beta-adrenoceptor agonist prenalterol was demonstrated. The inhibitory response to prenalterol showed a biphasic concentration-response curve. The muscarinic antagonist atropine produced an increase in the maximal response of the high potency component of the concentration-response curve for prenalterol and an increase in the sensitivity to isoprenaline. These results demonstrate the presence of a high cholinergic tone in the colon preparation of a magnitude that clearly reduces the sensitivity to beta-adrenoceptor agonists. The different responses to full and partial beta adrenoceptor agonists in the presence of increasing concentrations of muscarinic agonists may indicate that beta-adrenoceptors are located on two different functional units within the colon wall. PMID- 2897086 TI - Phorbol ester does not mimic, but antagonizes the alpha-adrenoceptor-mediated positive inotropic effect in the rabbit papillary muscle. AB - The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) was used to examine the hypothesis that phosphoinositide turnover is involved in the regulation of myocardial contractility mediated by stimulation of alpha-adrenoceptors in the mammalian cardiac muscle. Exposure of the isolated rabbit papillary muscle electrically driven at a rate of 1 Hz at a temperature of 37 degrees C to TPA in concentrations of 10-1000 nmol/l for 30 min did not affect the basal force of contraction. The concentration-response curve for the positive inotropic effect of (-)-phenylephrine mediated by stimulation of alpha-adrenoceptors in the presence of (+/-)-bupranolol (100 nmol/l) was shifted to the right and downward by TPA in concentrations of 30-1000 nmol/l, while the effect of (-)-phenylephrine mediated by stimulation of beta-adrenoceptors in the presence of prazosin (100 nmol/l) was not decreased, but slightly enhanced by exposure of the muscle to relatively low concentrations of TPA (10-100 nmol/l). Incubation of the membrane fraction isolated from the rabbit ventricular muscle with TPA in vitro under the same condition as employed in the physiological experiments decreased the specific binding of [3H]prazosin but not that of [3H]CGP-12177, while the non tumor promoting phorbol ester, alpha PDD, was ineffective. These results indicate that activation of protein kinase C by TPA does not mimic the positive inotropic effect of catecholamines mediated by activation of myocardial alpha adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897088 TI - Interrelationships between ornithine, glutamate, and GABA. II. Consequences of inhibition of GABA-T and ornithine aminotransferase in brain. AB - The objective of the present study was to compare the effects of elevation of GABA concentration and those of inactivation of L-ornithine: 2-oxoacid aminotransferase (OAT) on the in vivo metabolism of L-ornithine (Orn) in brain. Vigabatrin (4-aminohex-5-enoic acid) and gabaculine (5-amino-1,3-cyclohexadienyl carboxylic acid), two well known inactivators of GABA-T, were used to elevate brain GABA concentrations. The latter inactivates OAT also. Transamination of Orn is, from a quantitative point of view, a significant reaction in mouse brain. GABA is a feed-back regulator of OAT. Within GABAergic neurons Orn concentration may be regulated by endogenous GABA. Extensive inactivation of OAT causes a considerable increase of Orn concentration, both in synaptosomes and in non synaptosomal compartments. The results are compatible with a role of Orn as precursor of glutamate and/or GABA in certain neurons. PMID- 2897087 TI - Concentrations of physiologically important metal ions in glial cells cultured from chick cerebral cortex. AB - Energy dispersive x-ray fluorescence and atomic absorption spectroscopy were used to determine the concentrations of Mg, Ca, Mn, Fe, Zn, and Cu in primary cultures of astroglial cells from chick embryo cortex in chemically defined serum-free growth medium. The intracellular volume of cultured glia was determined to be 8.34 microliter/mg protein. Intracellular Mn, Fe, Zn, and Cu in these cells were ca. 10-200 microM, or 20-200 times the concentrations in the growth medium. Mg2+ was 7 mM in glial cells, only four-fold higher than in growth medium. Glutamine synthetase (GS), compartmentalized in glia, catalyzes a key step in the metabolism of neurotransmitter L-glutamate as part of the glutamate/glutamine cycle between neurons and glia. Hormones (insulin, hydrocortisone, and cAMP) added to growth medium differentially altered the activity of GS and the intracellular level of Mn(II), but not Mg(II). These findings suggest the possibility that glutamine synthetase activity could be regulated in brain by the intracellular levels of Mn(II) or the ratio of Mn(II)/Mg(II), which may in turn be controlled indirectly by means of transport processes that respond to hormones or secondary metabolic signals. PMID- 2897089 TI - B-lipotropin 61-76 and 61-91 fragments act as transglutaminase substrates in vitro. AB - Both alpha- and beta-endorphin were shown to incorporate radioactive polyamines during incubation in the presence of purified transglutaminase and Ca2+, spermine acting as the best acyl acceptor substrate. The endorphin labelling is dependent on the time of exposure to the enzyme and on the substrate concentration. In the absence of acyl acceptor polyamines, isotopically labelled beta-endorphin gives rise to high molecular weight radioactive polymer(s). Moreover, when different proteins acting as transglutaminase substrates are added, beta-endorphin produces heterologous structures. These data indicate that the glutamine-71 of the beta lipotropin chain, contained in both alpha- and beta-endorphin, functions as acyl donor substrate for the enzyme and that at least one beta-endorphin lysyl residue can serve as acyl acceptor. PMID- 2897090 TI - Co-localization of neurotensin- and cholecystokinin-like immunoreactivities in catecholamine neurons in the rat dorsomedial medulla. AB - Co-localization of neurotensin and cholecystokinin in tyrosine hydroxylase containing neurons in the nucleus tractus solitarius of the rat was demonstrated by immunocytochemistry with fluorescent double-staining combined with the peroxidase-antiperoxidase method. Co-localization of neurotensin/tyrosine hydroxylase or cholecystokinin/tyrosine hydroxylase was consistently found in small neurons in the region dorsomedial to the tractus solitarius at the level of the area postrema with high percentages of co-existence: 91.0% tyrosine hydroxylase-immunoreactive neurons contained neurotensin and 91.1% cholecystokinin, suggesting that they represent the same neurons. Accordingly, co localization of neurotensin and cholecystokinin was assessed on tyrosine hydroxylase-containing neurons bisected into two adjacent sections, and then identified in a certain number of the catecholamine neurons in this region. Furthermore these catecholamine neurons exhibited immunoreactivity for an adrenaline-synthesizing enzyme, phenylethanolamine N-methyltransferase. It was concluded that catecholamine, in particular adrenaline, neurons, characterized by co-localization of neurotensin and cholecystokinin, established a distinct subpopulation in the catecholaminergic system in the dorsomedial medulla of the rat. PMID- 2897091 TI - Neuropeptide tyrosine in the rat adrenal gland--immunohistochemical and in situ hybridization studies. AB - The adrenal gland of the rat was analysed with immunohistochemistry and antisera to neuropeptide tyrosine, to the catecholamine-synthesizing enzymes tyrosine hydroxylase, phenyl-ethanolamine-N-methyltransferase, and to acetylcholinesterase and with in situ hybridization using a nick-translated 280 base pair deoxyribonucleic acid probe coding for exon 2 of the rat neuropeptide tyrosine gene. Neuropeptide tyrosine-like immunoreactivity was observed in three structures: chromaffin cells, medullary ganglion cells and nerve fibers. The chromaffin cells were of both the noradrenaline- and adrenaline-type. The ganglion cells did not seem to contain any catecholamine-synthesizing enzymes but exhibited a strong immunoreaction for acetylcholinesterase. They were thus in all probability cholinergic neurons. In situ hybridization using the nick-translated deoxyribonucleic acid probe to rat neuropeptide tyrosine messenger ribonucleic acid revealed a very high-grain density over the ganglion cells, a moderate density over the chromaffin cells and a low background over cortex, in agreement with the immuno-histochemical demonstration of neuropeptide tyrosine-like immunoreactivity both in chromaffin and ganglion cells. The intense neuropeptide tyrosine-like immunoreactivity and low content of neuropeptide tyrosine messenger ribonucleic acid suggest that the chromaffin cells have fairly large peptide stores but that the peptide turnover is low. In contrast, the ganglion cell bodies seem to contain low amounts of neuropeptide tyrosine-like immunoreactivity but exhibit a high neuropeptide tyrosine synthesis rate. Preliminary studies with the amine-depleting drug reserpine revealed an increase in messenger ribonucleic acid both in ganglion cells and medullary cells. In the chromaffin cells the highest activity was seen 3 and 4 days after injection, and the levels were down to normal after 8 days. The present findings demonstrate neuropeptide tyrosine synthesis and storage in two cell populations in the adrenal medulla. In situ hybridization with its cellular resolution can provide information on possible differential effects of drugs and experimental procedures on these two neuropeptide tyrosine stores. PMID- 2897092 TI - GABA release from Xenopus retina does not correlate with horizontal cell membrane potential. AB - The relationship between horizontal cell membrane potential and the release of GABA was explored in the retina of Xenopus laevis. The intracellularly recorded membrane potential of horizontal cells was monitored while the retina was exposed to different concentrations of depolarizing agents. The dose-response curves obtained revealed a rise from 5 to 95% maximum depolarization in 0.5-1.5 log unit concentration change. The molar concentrations that elicited a 20 mV depolarization were 40 mM (potassium), 0.8 mM (glutamate), 0.8 mM (glycine), 5 microM (kainate) and 1.3 microM (quisqualate). Autoradiography revealed that radiolabel was accumulated almost exclusively by horizontal cells when isolated retinas were incubated in medium containing 1 microM [3H]GABA. Thus, retinal release of radioactivity was used as a measure of [3H]GABA release from horizontal cells. Endogenous GABA released from retinas was measured using high performance liquid chromatography and was taken to reflect both amacrine and horizontal cell GABA pools. The release of both [3H]GABA and endogenous GABA was stimulated by glutamate, kainate and potassium, but not by glycine or quisqualate. Similar dose-response curves for GABA release and for depolarization were obtained in the case of potassium and kainate but not for glutamate. Potassium-evoked release either of endogenous GABA or [3H]GABA was both calcium- and sodium-dependent, whereas kainate- or glutamate-evoked GABA release was sodium-dependent but calcium-independent. The results indicate that depolarization per se is not necessarily associated with transmitter release in Xenopus retinal horizontal cells. It is suggested that the action of a given neurotransmitter upon the efflux of GABA from horizontal cells may depend on the degree to which it modifies the sodium conductance of the horizontal cell. PMID- 2897094 TI - Glutamate phase shifts circadian activity rhythms in hamsters. AB - The suprachiasmatic nuclei (SCN) have been identified as a pacemaker for many circadian rhythms in mammals. Photic entrainment of this pacemaker can be accomplished via the direct retino-hypothalamic tract (RHT). Glutamate is a putative transmitter of the RHT. In the present study it is demonstrated that glutamate injections in the SCN cause phase shifts of the circadian activity rhythm of the hamster. In contrast, glutamate injections outside the SCN or vehicle injections inside the SCN did not affect the circadian phase. These data suggest that glutamate could be involved in photic entrainment of the circadian pacemaker. PMID- 2897093 TI - Evidence for a role of haloperidol-sensitive sigma-'opiate' receptors in the motor effects of antipsychotic drugs. AB - Haloperidol exhibits a high affinity for a subclass of sigma- "opiate" binding sites which have a unique anatomic distribution and a unique drug selectivity pattern. These binding sites differ from phencyclidine-sensitive sigma-receptors and are found in many brain areas involved in the control of movement. 1,3-Di-o tolylguanidine (DTG), a highly selective ligand for the haloperidol-sensitive sigma-receptor, produced marked dystonia in rats after microinjection into the red nucleus, a motor area rich in this receptor. Haloperidol and another sigma ligand [(+)-SKF 10,047] produced similar effects. On the other hand, clozapine, an antipsychotic drug which fails to bind to sigma-receptors and fails to induce movement disorders in humans, failed to induce these dystonic reactions in rats. Phencyclidine was also without effect, as were injections of the active compounds in sites distant to the red nucleus. Microinjections of DTG in the substantia nigra produced vigorous contralateral circling behavior at extremely low doses. These findings suggest that sigma-binding sites represent biologically functional receptors that are active in the neural control of movement. Since haloperidol (and many other antipsychotic drugs) exhibit an affinity for sigma-receptors which is at least equal to its affinity for dopamine receptors, these data raise the further possibility that sigma-receptors are involved in the motor side effects of antipsychotic drugs. PMID- 2897095 TI - Effects of chemical stimulation of paraventricular nucleus on adrenal and renal nerve activity in rats. AB - The effects of stimulation of the hypothalamic paraventricular nucleus (PVN) by L glutamate on blood pressure and ongoing activities of adrenal and renal sympathetic nerves were examined in anesthetized rats. Microinjection of excitatory amino acid, L-glutamate (100 nmol in 200 nl saline), into the unilateral PVN resulted in an increase in the ipsilateral adrenal nerve activity, while it resulted in decreases in renal nerve activity and arterial blood pressure. After severance of bilateral carotid sinus and vagal nerves, the decreased response of blood pressure to the same stimulus did not change, while the decreased response of renal nerve activity was almost abolished, and the increased response of adrenal nerve activity still remained, though it slightly attenuated. The involvements of baroreceptor afferents and vagal afferents in these responses were discussed. PMID- 2897096 TI - Increase in the stimulation-induced overflow of excitatory amino acids from hippocampal slices: interaction between low glucose concentration and fluoroacetate. AB - To see whether the enhanced evoked release of aspartate and glutamate in the presence of low glucose concentration is due to a decreased glial uptake, the electrical-field stimulation induced release of aspartate and glutamate was measured in rat hippocampal slices in the presence of 5 or 0.2 mM glucose and of graded concentrations of fluoroacetate, a specific inhibitor of glial tricarboxylic acid cycle. In 5 mM glucose, fluoroacetate increased the overflow of both excitatory amino acids equally in a dose-dependent manner, with a maximal effect obtained at 2 mM. This maximal increase of glutamate overflow was about the same as caused by 0.2 mM glucose, but low glucose increased aspartate overflow 5 times more than did fluoroacetate. Fluoroacetate failed to increase any further the large evoked overflow of either glutamate or aspartate induced by 0.2 mM glucose. The absence of an additive effect of fluoroacetate and of low glucose suggests that under both conditions the increased overflow of glutamate is due to a reduced glial uptake. In low glucose an increased synthesis also contributes to the additional large release of aspartate. PMID- 2897097 TI - Australian Neuroscience Proceedings. Abstracts of the eighth meeting of the Australian Neuroscience Society. Canberra, Australia, February 9-11, 1988. PMID- 2897099 TI - Abstracts of the sixth national meeting of the Brain Research Association. London, U.K., 28-30 March 1988. PMID- 2897098 TI - Abstracts of the ninth annual conference of the Hong Kong Society of Neurosciences. Hong Kong, September 8-10, 1987. PMID- 2897100 TI - Abstracts of the Brain Research Association meeting, Mechanisms of Recovery of Function after Brain Damage. Oxford, U.K., 11 January 1988. PMID- 2897101 TI - Specificity of carcinoembryonic antigen, gastrointestinal cancer-associated antigen, tissue polypeptide antigen, fibrinopeptide A and gamma glutamyltransferase in the diagnosis and follow-up of gastric cancer. AB - The usefulness and specificity of the main tumor markers (carcinoembryonic antigen, CEA; gastrointestinal cancer-associated antigen, GICA; tissue polypeptide antigen, TPA; fibrinopeptide A, FpA; gamma-glutamyltransferase, gamma GT) have been investigated in the diagnosis and follow-up of the circumscribed and disseminated gastric cancers (GCs). The comprehensive evaluation of all of these markers has given the most reliable results. For the diagnosis and follow up of GCs, the present study has shown that the sensitivity and specificity of the above markers have the following decreasing order: FpA, TPA, GICA, CEA, gamma GT. However gamma-GT has proved to be a reliable index of the presence of hepatic metastases. PMID- 2897102 TI - Common site of mutation in the erbB gene of avian erythroblastosis virus mutants that are temperature sensitive for transformation. AB - The genome of the avian erythroblastosis virus temperature sensitive mutant ts34 was cloned from a cell line that was shown to contain a single integrated copy of the virus. The mutation was localized to the v-erbB gene by making chimeric viruses between the mutant genome and that of wildtype. Sequencing of the mutant v-erbB gene revealed a single amino acid change of a histidine to an aspartate residue at a position equivalent to amino-acid 826 of the human epidermal growth factor receptor. Interestingly this is the identical mutation to that recently reported for another temperature sensitive mutant ts167, indicating that this may be a hot spot for mutations in the v-erbB gene that give rise to ts transformation mutants. In addition, the different biological phenotypes of ts34 and ts167 are suggested to be due to an additional mutation in v-erbA in ts167. PMID- 2897103 TI - Chromosomal location of Evi-1, a common site of ecotropic viral integration in AKXD murine myeloid tumors. AB - The chromosomal location of Evi-1, a common site of ecotropic viral integration in AKXD murine myelogenous leukemias, was determined by recombinant inbred and conventional backcross analyses. We mapped Evi-1 to a location approximately 15 cM distal to the carbonic anhydrase locus on murine Chromosome 3. The chromosomal location of the proto-oncogene Nras, and two growth factors, epidermal growth factor (Egf), and the beta subunit of nerve growth factor (Ngfb), which had previously been assigned to Chromosome 3 by somatic cell hybrid analysis, were also determined. The location of Evi-1 is distinct from these three loci and from all other proto-oncogenes, common sites of viral integration, or growth factor loci previously mapped in mouse chromosomes. These results suggest that Evi-1 represents a new locus involved in myeloid disease. PMID- 2897104 TI - c-Ha-ras-1 polymorphism in human breast carcinomas: evidence for a normal distribution of alleles. AB - Analysis of the c-Ha-ras-1 locus for restriction fragment length polymorphism was determined by Southern blot hybridization in 112 specimens of primary breast carcinoma. Normal cell samples were lymphocytes obtained from 61 of these breast cancer patients and from 62 healthy donors. Our data indicate that the distribution of c-Ha-ras-1 alleles in breast carcinoma patients did not significantly differ from that found in normal individuals. In addition the loss of one allele detected in 5 tumor samples was not correlated to the aggressiveness of breast cancer. Consequently our data imply that hereditary predisposition to breast cancer is not associated with the c-Ha-ras-1 polymorphism as previously reported. PMID- 2897105 TI - [Cryptorchism--pathogenesis, diagnosis and therapy]. PMID- 2897106 TI - [Cryptorchism--an unsolved problem?]. PMID- 2897107 TI - Zinc competitively inhibits calcium-dependent release of transmitter at the mouse neuromuscular junction. AB - The effect of zinc on the release of transmitter was investigated in preparations of mouse diaphragm by conventional microelectrode techniques. The frequency (F) of miniature end-plate potentials (MEPPs), elevated by Ca2+ in high K+ medium, was reduced by zinc in a concentration-dependent fashion. When the extracellular concentration of Ca2+ ([Ca2+]o) was varied in the absence of zinc, a linear relationship between log(F) and log([Ca2+]o) was obtained. When the effect of zinc was depicted graphically, it was found that zinc shifted the relationship between log(F) and log([Ca2+]o) to the right, with respect to the control in the absence of zinc, without altering the slope. Zinc also reduced the quantal content (m) of end-plate potentials (EPPs). As [Ca2+]o was varied in the absence of zinc, a linear relationship between ln(m) and ln([Ca2+]o) was observed. Zinc shifted this linear relationship between ln(m) and ln([Ca2+]o) to the right, with respect to the control, without altering the slope. Thus, zinc reduced both the asynchronous and the phasic release of transmitter. These results suggest that zinc competes with Ca2+, and this conclusion is confirmed by examination of a modified Lineweaver-Burk plot of the data. Zinc probably inhibits the entry of Ca2+ into the nerve terminals, thereby inhibiting transmitter release. PMID- 2897108 TI - Isolation and mapping of a polymorphic DNA sequence (pTHI54) on chromosome 1p [D1S62]. PMID- 2897109 TI - Isolation and mapping of a polymorphic DNA sequence (pEFD53.2) on chromosome 1 [D1S73]. PMID- 2897110 TI - Isolation and mapping of a polymorphic DNA sequence (pTHH55) on chromosome 15 [D15S27]. PMID- 2897111 TI - Isolation and mapping of a polymorphic DNA sequence (pTHH14) on chromosome 12p [D12S16]. PMID- 2897112 TI - Isolation and mapping of a polymorphic DNA sequence (cMHZ47) on chromosome 13 [D13S52]. PMID- 2897113 TI - Isolation and mapping of a polymorphic DNA sequence (cKKA39) on chromosome 14 [D14S23]. PMID- 2897114 TI - Isolation and mapping of a polymorphic DNA sequence (pCMM17.1) on chromosome 10 [D10S16]. PMID- 2897115 TI - Isolation and mapping of a polymorphic DNA sequence (pCMM65) on chromosome 16 [D16S84]. PMID- 2897116 TI - A 0.5 kb insert polymorphism 3' to the c-myc gene. PMID- 2897117 TI - NcoI and HinfI RFLPs detected with a dihydropteridine reductase cDNA probe. PMID- 2897118 TI - Anticataleptic effect of taurine: interaction with antiparkinsonian agents. AB - The influence of taurine on cataleptogenic effect of neuroleptics was investigated in male Wistar rats. It was found that taurine 900 micrograms/rat icv reduced significantly haloperidol or fluphenazine-induced catalepsy. In rats receiving taurine in a dose of 450 micrograms, not influencing catalepsy, with low doses of anticholinergic antiparkinsonian agents (trihexyphenidyl and pridinol) strong anticataleptic effect was observed. The results suggest that taurine facilitates neurotransmission in nigrostriatal dopaminergic neurons. PMID- 2897119 TI - Diagnosis and management of pain in patients with cancer. PMID- 2897120 TI - Mechanochemical coupling in synthetic polypeptides by modulation of an inverse temperature transition. AB - For the polypentapeptide of elastin, (L-Val-L-Pro-Gly-L-Val-Gly)n, and appropriate analogs when suitably cross-linked, it has been previously demonstrated that development of elastomeric force at fixed length and length changes at fixed load occur as the result of an inverse temperature transition, with the temperature of the transition being inversely dependent on the hydrophobicity of the polypeptide. This suggests that at fixed temperature a chemical means of reversibly changing the hydrophobicity could be used for mechanochemical coupling. Evidence for this mechanism of mechanochemical coupling is given here with a 4%-Glu-polypentapeptide, in which the valine in position 4 is replaced in 1 out of 5 pentamers by a glutamic acid residue. Before cross linking, the temperature for aggregation of 4%-Glu-polypentapeptide is remarkably sensitive to pH, shifting from 25 degrees C at pH 2 to 70 degrees C at pH 7.4 in phosphate-buffered saline (PBS). At 37 degrees C, the cross-linked 4%-Glu polypentapeptide matrix in PBS undergoes a pH-modulated contraction and relaxation with a change from pH 4.3 to 3.3 and back. The mean distance between carboxylates at pH 4.3 in the elastomeric matrix is greater than 40 A, twice the mean distance between negatively charged species in PBS. Accordingly, charge charge repulsion is expected to make little or no contribution to the coupling. Mechanochemical coupling is demonstrated at fixed load by monitoring pH dependence of length and at constant length by monitoring pH dependence of force. To our knowledge, this is the first demonstration of mechanochemical coupling in a synthetic polypeptide and the first system to provide a test of the recent proposal that chemical modulation of an inverse temperature transition can be a mechanism for mechanochemical coupling. It is suggested that phosphorylation and dephosphorylation may modulate structure and forces in proteins by locally shifting the temperatures of inverse temperature transitions. PMID- 2897121 TI - Chromosomal mapping of the structural gene coding for the mouse cell adhesion molecule uvomorulin. AB - The gene coding for the mouse cell adhesion molecule uvomorulin has been mapped to chromosome 8. Uvomorulin cDNA clone F5H3 identified restriction fragment length polymorphisms in Southern blots of genomic DNA from mouse species Mus musculus domesticus and Mus spretus. By analyzing the segregation pattern of the gene in 75 offspring from an interspecific backcross a single genetic locus, Um, was defined on chromosome 8. Recombination frequency between Um and the co segregating loci serum esterase 1 (Es-1) and tyrosine aminotransferase (Tat) places Um about 14 centimorgan (cM) distal to Es-1, and 5 cM proximal to Tat. In situ hybridization of uvomorulin [3H]cDNA to mouse metaphase chromosomes located the Um locus close to the distal end of chromosome 8 (bands C3-E1). Since uvomorulin is evolutionarily highly conserved, its chromosomal assignment adds an important marker to the mouse genetic map. PMID- 2897122 TI - Doxorubicin cardiotoxicity may be caused by its metabolite, doxorubicinol. AB - Doxorubicin (former generic name, adriamycin), a highly effective anticancer drug, produces cardiotoxicity, which limits its therapeutic potential. The mechanism of this cardiotoxicity has remained elusive. Our data suggest that this toxicity could involve doxorubicinol, the primary circulating metabolite of doxorubicin. Doxorubicinol was markedly more potent than doxorubicin at compromising both systolic and diastolic cardiac function. Similarly, doxorubicinol was much more potent than doxorubicin at inhibiting the calcium pump of sarcoplasmic reticulum [ATP phosphohydrolase (Ca2+-transporting), EC 3.6.1.38], the Na+/K+ pump of sarcolemma [ATP phosphohydrolase (Na+/K+ transporting), EC 3.6.1.37], and the F0F1 proton pump of mitochondria [ATP phosphohydrolase (H+-transporting, EC 3.6.1.34]. Our finding that this highly toxic metabolite was produced by cardiac tissue exposed to doxorubicin suggests that doxorubicinol could accumulate in the heart and contribute significantly to the chronic cumulative cardiotoxicity of doxorubicin therapy. Our observation that doxorubicin was more potent than doxorubicinol in inhibiting tumor cell growth in vitro suggests that the cardiotoxicity of doxorubicin is dissociable from its anticancer activity. PMID- 2897123 TI - Molecular cloning of human T-cell lymphotrophic virus type I-like proviral genome from the peripheral lymphocyte DNA of a patient with chronic neurologic disorders. AB - Human T-cell lymphotropic virus type 1 (HTLV-I), the etiologic agent of human T cell leukemia, has recently been shown to be associated with neurologic disorders such as tropical spastic paraparesis, HTLV-associated myelopathy, and possibly with multiple sclerosis. In this communication, we have examined one specific case of neurologic disorder that can be classified as multiple sclerosis or tropical spastic paraparesis. The patient suffering from chronic neurologic disorder was found to contain antibodies to HTLV-I envelope and gag proteins in his serum and cerebrospinal fluid. Lymphocytes from peripheral blood and cerebrospinal fluid of the patient were shown to express viral RNA sequences by in situ hybridization. Southern blot analysis of the patient lymphocyte DNA revealed the presence of HTLV-I-related sequences. Blot-hybridization analysis of the RNA from fresh peripheral lymphocytes stimulated with interleukin 2 revealed the presence of abundant amounts of genomic viral RNA with little or no subgenomic RNA. We have cloned the proviral genome from the DNA of the peripheral lymphocytes and determined its restriction map. This analysis shows that this proviral genome is very similar if not identical to that of the prototype HTLV-I genome. PMID- 2897126 TI - [Quality in hospitals]. PMID- 2897124 TI - Neuroanatomical localization and quantification of amyloid precursor protein mRNA by in situ hybridization in the brains of normal, aneuploid, and lesioned mice. AB - Amyloid precursor protein mRNA was localized in frozen sections from normal and experimentally lesioned adult mouse brain and from normal and aneuploid fetal mouse brain by in situ hybridization with a 35S-labeled mouse cDNA probe. The highest levels of hybridization in adult brain were associated with neurons, primarily in telencephalic structures. The dense labeling associated with hippocampal pyramidal cells was reduced significantly when the cells were eliminated by injection of the neurotoxin ibotenic acid but was not affected when electrolytic lesions were placed in the medial septum. Since the gene encoding amyloid precursor protein has been localized to mouse chromosome 16, we also examined the expression of this gene in the brains of mouse embryos with trisomy 16 and trisomy 19 at 15 days of gestation. RNA gel blot analysis and in situ hybridization showed a marked increase in amyloid precursor protein mRNA in the trisomy 16 mouse head and brain when compared with euploid littermates or with trisomy 19 mice. PMID- 2897127 TI - Interaction of antidepressants and neuroleptics with histamine stimulated parietal cell adenylate cyclase and H+ secretion. AB - The tricyclic antidepressants trimipramine and doxepin, and the neuroleptic agents trifluoperazine and haloperidol were tested for their effect on histamine H2-receptor-mediated adenylate cyclase activity and H+ secretion in guinea-pig parietal cells. All compounds inhibited histamine-stimulated adenylate cyclase and H+ secretion in a concentration-dependent manner. The antisecretory potency was 1-2 orders of magnitude higher than that for adenylate cyclase inhibition. All drugs caused a rightward shift in the concentration-response curves of histamine-induced adenylate cyclase activation with Schild-plot lines having a slope significantly different from unity. Histamine-stimulated H+ secretion was inhibited by the drugs in a noncompetitive fashion. These results demonstrate that antidepressants and neuroleptics interfere noncompetitively with the parietal cell histamine H2-receptor and that this receptor blocking activity is not related to the antisecretory activity of the drugs. PMID- 2897125 TI - Absence of acute doxorubicin-induced dysfunction of heart mitochondrial oxidative phosphorylation and creatine kinase activities. AB - Since reductions in cardiac high-energy phosphate content and dysfunction of mitochondrial activities have been demonstrated after doxorubicin exposure, one mechanism of doxorubicin cardiotoxicity has been thought to be an interference with mitochondrial energy metabolism. To determine whether mitochondrial dysfunction is induced by acute drug exposure, isolated rat hearts were perfused with 10(-5) M doxorubicin for 70 min followed by mitochondrial isolation. Rates of electron transport, creatine kinase activity, acceptor control, respiratory control, and ADP/O ratios were assayed and correlated to doxorubicin-induced abnormalities in left ventricular function. At doses of doxorubicin sufficient to cause a marked deterioration of left ventricular systolic pressure and a rise in end-diastolic pressure, no decreases were noted in the measured mitochondrial parameters with either glutamate plus malate or succinate as respiratory substrates. In fact, in some cases the rates of electron transport were higher in mitochondria isolated from the treated hearts. In addition, isolated heart mitochondria were directly incubated in doxorubicin at doses as high as 10(-4) M for up to 70 min at 0 and 20 degrees C and 1.5 min at 37 degrees C. Under these conditions functional impairment of mitochondrial respiration was also not detected. Therefore, it appears that acute doxorubicin cardiotoxicity cannot be related to primary mitochondrial defects in high-energy phosphate metabolism. These data lend further support to the notion that doxorubicin cardiotoxicity may be fundamentally related to changes in coronary vascular resistance and resultant damage induced by hypoperfusion. PMID- 2897128 TI - Intestinal transport in constipation and diarrhoea. AB - Approximatively 10 liters of fluid enter the gastrointestinal tract with food and endogenous secretions, and only less than 100 ml or 1% leave it with the faeces. Minor changes of this equilibrium in the intestinal transport may cause diarrhoea or constipation. Functions of small and large intestine differ markedly in transport of electrolytes and water. The relatively leaky epithelium of the small intestine allows for rapid equilibrium of osmolality in both directions while the tight epithelium of the colon preserves electrolytes and water once they have been absorbed. It may compensate secretory diarrhoea of the small intestine for instance caused by bacterial toxins to a certain degree unless it is overwhelmed leading to an overflow type of diarrhoea. On the other hand, small changes of net fluid transport in the colon in either direction will lead to diarrhoea or constipation since there is no compensating mechanism behind it. Mechanisms involved in the regulation of transintestinal electrolyte and water movements are the energy providing Na+,K+-ATPase, the mediators of membrane permeability and active Cl- secretion such as cAMP and Ca2+ and substances affecting the tight junctions. Various substances may affect one or more of these regulatory mechanisms. Laxatives are one of those. PMID- 2897129 TI - Denial of lineage: clinical investigation of 50 cases. AB - Fifty randomly selected Chinese schizophrenic patients with denial of lineage were investigated. This delusion concerns the generation of parents, sisters, but not the offspring. Twenty-four of them manifested delusion of high-ranking lineage or of distinguished leadership lineage. Denial of lineage, involving the delusion of high-ranking lineage and the delusion of leadership lineage, may occur at the onset or during the course of schizophrenia. The clinical characteristics of this delusion are described and its concept, diagnosis, differential diagnosis, course and also possible mechanism are discussed. One possible mechanism is of psychodynamical origin. Emotional conflicts resulting from dissatisfaction of the primary need of being loved from birth may contribute to the onset of the denial of lineage. The second possible mechanism is a sociocultural fact. Far Eastern culture is based on the clan whereas occidental culture is based on the self. Thus can observe the denial of lineage in the Far East, but in the occident we can experience instead the idea of surmounting our self so as to be god or now to experience the omnipotence in form of technical ideas, e.g. the rays. PMID- 2897130 TI - Duodenal carcinoid tumours, phaeochromocytoma and neurofibromatosis: islet cell tumour, phaeochromocytoma and the von Hippel-Lindau complex: two distinctive neuroendocrine syndromes. AB - To clarify neuroendocrine syndromes we have reviewed the association of neurofibromatosis with carcinoid tumours and of neurofibromatosis, phaeochromocytoma or von Hippel-Lindau complex with either carcinoid or islet cell tumours. In nine cases of neurofibromatosis with a carcinoid tumour studied all carcinoid tumours were in the duodenum, were distinctive histologically and had widespread somatostatin immunoreactivity. The duodenum was the primary site in 18 of 20 further published cases of carcinoid tumour and neurofibromatosis. Phaeochromocytoma was also present in six of these 27 cases with neurofibromatosis and duodenal carcinoid tumour. Six patients have been reported with Von Hippel-Lindau complex, phaeochromocytoma and islet cell tumour. A further 11 patients showed phaeochromocytoma and islet cell tumour. No cases of Von Hippel-Lindau complex had a carcinoid tumour, and no cases of neurofibromatosis had an islet cell tumour. We conclude that the association of neurofibromatosis, duodenal carcinoid tumour and phaeochromocytoma forms a distinctive neuroendocrine syndrome, sharply separated from the association of Von Hippel-Lindau complex with islet cell tumour and phaeochromocytoma. This separation is important in pathogenesis, diagnosis and clinical management. PMID- 2897131 TI - [The nonadrenergic, noncholinergic neuropeptide system and asthma]. AB - An understanding of the non adrenergic non cholinergic nervous system and its implication in the pathogenesis of asthma would benefit by the identification and localisation of the numerous natural bioactive peptides at the pulmonary level. In the past few years two components of the non adrenergic non cholinergic nervous system have been characterised. A bronchodilator component which would be mediated by "vaso-active intestinal peptide" (VIP) and the "peptide histidine methionine" (PHM). A broncho-constrictor component which would be mediated by the neurokinins (substance P (SP), neurokinin A (NKA) and the "calcitonin gene related peptide" (CGRP)). These neuropeptides, in vitro as well as in vivo, have effects which are not limited to the regulation of bronchial smooth muscle tone. In effect, they may intervene in the regulation of vascular tone, in the production of mucous and in the expression of immediate hypersensitivity reactions at pulmonary level. Several neuropeptides are present or co-exist with classical neurotransmitter in the afferent nerve endings of the pulmonary efferents. This co-existence of several neurotransmitters in the same nervous fibres raised the questions as to their interactions at the pre or post synaptic level. The implication of these neuropeptides in the pathogenesis of asthma rests on numerous experimental arguments. This recent aspect in the pathophysiology of asthma allows us to hope for new therapeutic approaches. PMID- 2897132 TI - Regulatory peptides. PMID- 2897133 TI - Radioimmunotherapy with alpha-particle-emitting immunoconjugates. AB - Alpha particles are energetic short-range ions whose higher linear energy transfer produces extreme cytotoxicity. An alpha-particle-emitting radioimmunoconjugate consisting of a bismuth-212-labeled monoclonal immunoglobulin M specific for the murine T cell/neuroectodermal surface antigen Thy 1.2 was prepared. Analysis in vitro showed that the radioimmunoconjugate was selectively cytotoxic to a Thy 1.2+ EL-4 murine tumor cell line. Approximately three bismuth-212-labeled immunoconjugates per target cell reduced the uptake of [3H]thymidine by the EL-4 target cells to background levels. Mice inoculated intraperitoneally with EL-4 cells were cured of their ascites after intraperitoneal injection of 150 microcuries of the antigen-specific radioimmunoconjugate, suggesting a possible role for such conjugates in intracavitary cancer therapy. PMID- 2897135 TI - Observations with minipress. PMID- 2897134 TI - [The enzyme diagnosis of liver involvement in meningococcal infection]. AB - A complex of blood enzymes (AST, ALT, AP, GTT) was studied in 84 patients with generalized forms of MI. The study showed that signs of liver involvement were noted in 15.4% of the patients on the 1st day of disease. Laboratory signs of cytolysis and cholestasis were revealed in most examinees on the 7th-15th day of disease during a dynamic follow-up. The most noticeable syndromes were revealed in young patients (30 persons) with brain edema (42.2%). Primary liver involvement (i. e. noted on admission to hospital) in 6 patients was associated with MI toxic effects, in 7 patients--with a severe concomitant pathology of the pulmonary and cardiovascular system. Delayed liver involvement was detected in 55.3% of the young patients and in half of the elderly patients. It was established that a course of disease was accompanied by the affection of many organs from the first days complicating the interpretation of enzymological data therefore requiring combined enzymological investigations. PMID- 2897136 TI - [The effect of preventative carazolol treatment on stress reactions in boars during semen collection]. AB - The effect of the beta adrenoceptor blocking agent carazolol on heart and circulatory system, on blood values of the acid-base-equilibrium and on plasma enzymes such as creatine-kinase (CK) and aspartate-amino-transferase (ASAT) was investigated in four clinical healthy boars of the German Landrace and four boars of the Pietrain race before, during and after ejaculation at the phantom. The heart rate during semen collection increased less with treatment than it did without it. The relative diastolic time during exertion was prolonged by carazolol in those boars, which also without pharmacological influence had a very short relative diastolic time. By carazolol injection the systolic blood pressure could be decreased most in those boars, which without treatment had the highest rise of systolic blood pressure during semen collection. Furthermore it was shown, that the highest lactate values, which were found in some boars of the Pietrain race, were reduced most by the influence of carazolol. The blood values of the acid-base-equilibrium were highly negative correlated with the lactate values and changed according to them. The enzyme activities (CK and ASAT) 24 h after semen collection were not influenced by carazolol. Individual differences from boar to boar were evident in all examined parameters and were independent of the effects of carazolol treatment. PMID- 2897137 TI - [Stress reactions in clinically healthy sows at the time of birth and their relationship to the CK test]. AB - Concentrations of the enzymes creatine kinase (CK) and aspartate aminotransferase (ASAT/GOT) were determined in plasma of 100 gilts and 175 sows at the 112. day of pregnancy and one day after parturition. Gilts and sows were divided into a stress resistant (n = 146) and a stress susceptible group (n = 129) following the creatine-kinase-test carried out after the performance test period at a body weight of 90 kg (CK-90). Stress susceptible gilts and sows showed higher CK values before and especially after parturition than stress resistant ones. Significant correlations were demonstrable between CK-90 and the CK values before and after parturition (r = 0.5). Regarding body temperature, respiration rate and heart frequency as well as the percentage of stillborn piglets, the two groups of sows did not differ from each other. The increase of enzyme activities after parturition was not influenced by prophylactic treatment with prostaglandin-F2 alpha or beta receptor blocking agent. The beta blocking agent Carazolol, however, caused a transient depression of heart rate after parturition. PMID- 2897138 TI - [Anesthesia in swine]. AB - Pigs are not only anaesthetized in case of operations but often also if diagnostic and therapeutic procedures are necessary. Choice of the anaesthetic and way of application depend on the size of the patient and the indication. The only important local anaesthesia in pigs is epidural anaesthesia. It is indicated in all longer lasting painful procedures in caudal regions. The technique of this anaesthesia is described. From the possible methods of general anaesthesias, in practice injection anaesthesia has been generally accepted for several reasons. Together with barbiturate anaesthesia neurolept-analgesia with Azaperone- Metomidate has become more and more important, because with this form of anaesthesia the technically easy intra-abdominal application is possible in pigs under 15 kg of body weight. PMID- 2897139 TI - Species variations in biliary excretion of glutathione-related thiols and methylmercury. AB - The biliary excretion of methylmercury is thought to be related to the biliary excretion of nonprotein thiols in rats. Species differences in biliary excretion of glutathione (GSH) and related thiols are unknown; therefore, the relationship between the biliary excretion of GSH-related thiols and methylmercury in five species was studied. The biliary excretion rate of GSH-related thiols and disulfides was 369, 192, 94, 50, and 19 nmol/min/kg for mice, rats, hamsters, guinea pigs, and rabbits, respectively. The main thiol in mouse, hamster, and rat bile was GSH, whereas guinea pig and rabbit bile contained mainly cysteinylglycine (Cys-Gly). The larger percentage of Cys-Gly in guinea pig and rabbit bile was correlated with their greater hepatic gamma glutamyltranspeptidase (GGT) activity than that observed in the other species. The biliary excretion rate (nmol/min/kg) of methylmercury was approximately 0.8 in mice, rats, and hamsters compared to significantly lower rates in guinea pigs and rabbits (0.15 and 0.03, respectively). It is concluded that the species specific composition of GSH-related thiols and disulfides in bile is related to species variations in hepatic GGT activity, and that the species variation in biliary excretion of GSH-related thiols does not entirely account for the species variation in methylmercury excretion, indicating other factors are also apparently involved in determining the rate of biliary excretion of methylmercury. PMID- 2897140 TI - The stimulation of somatostatin release by hpGRF44 from rat hypothalamic cells and fragments in vitro. AB - Growth hormone releasing factor (GHRF) was examined to determine whether it affects somatostatin (SRIF) release from cultured rat hypothalamic cells and fragments in vitro. The hypothalami of rat fetuses were collected on the 17th day of pregnancy under a dissection microscope. Thirty hypothalami were placed in phosphate buffered saline, and the cells were dispersed with 0.1% collagenase. The dispersed cells were cultured in Dulbecco's modified Eagle medium (DMEM) containing 10% horse serum and 2.5% fetal calf serum at 37 degrees C under 5% CO2 in air. On the 12th day of culture, the cells were washed with Krebs Ringer bicarbonate buffer containing glucose (KRBG), and then incubated with KRBG for 1 hour. The medium was replaced with KRBG alone (control) or KRBG containing test substances, and incubated for another hour. SRIF released into the medium was quantitated by RIA. The mean basal release of SRIF was 14.7 +/- 0.9 pg/dish/hour. One-tenth, 1, and 10nM hpGRF44 stimulated SRIF release by 1.4, 1.5, and 1.8 fold respectively in a dose-related manner. Ten nM ovine corticotropin releasing factor (o-CRF) also stimulated SRIF release by 2.3 fold. One, 10, and 100 nM hpGRF44, 10nM o-CRF, 10nM thyrotropin releasing hormone (TRH) and 60 mM K+ also stimulated SRIF release from rat hypothalamic fragments. Removal of Ca++ from the medium resulted in a decrease of basal release of SRIF. In Ca++ free medium, 10nM hpGRF44 failed to release SRIF. One-tenth nM hpGRF44, 10nM GnRH, and 10nM VIP have no effect on SRIF release statistically. The results of this study demonstrate that a high concentration of GHRF stimulates SRIF release from the hypothalamus in vitro, suggesting a possibility that GHRF may increase the release of SRIF from the median eminence and the hypothalamus in vivo under certain conditions. PMID- 2897142 TI - [Stimulants]. PMID- 2897141 TI - Absence of a facilitory role for NK 1.1-positive donor cells in engraftment across a major histocompatibility barrier in mice. AB - Ex vivo T cell depletion of donor marrow grafts in humans and mice has virtually eliminated severe graft-versus-host disease (GVHD). However, as a consequence of T cell depletion, sustained donor cell engraftment is likely compromised. Since the majority of T cell depletion techniques also deplete natural killer (NK) cells, we investigated the role of donor NK cells in engraftment and GVHD in a murine model. Using a monoclonal antibody directed against an NK-specific epitope, we have selectively depleted NK cells while preserving donor marrow T cells. In an established model of engraftment, selective NK depletion demonstrated that removal of donor NK cells did not impair the engraftment process under conditions in which donors and recipients are major histocompatibility complex-disparate. In contrast, recipients of anti-Thy 1.2 plus complement (C')-treated marrow grafts had a significantly higher incidence of either partial engraftment or graft rejection as compared with recipients of selective NK-depleted donor grafts or control grafts. In addition, we have observed that NK-specific depletion of donor marrow/splenocyte inocula does not alter the incidence of GVHD. Recipients of NK-depleted donor grafts developed lethal acute GVHD, whereas recipients of anti-Thy 1.2-depleted donor grafts did not (P less than 0.0001). Interestingly, NK 1.1-depleted donor graft recipients had a significantly increased mortality in comparison with control groups receiving C'-treated grafts (P = 0.04) or anti-Thy 1.2 plus C'-treated grafts (P less than 0.05). Thus, NK depletion may reduce immunosurveillance, thereby increasing the risk of posttransplant infection. We conclude from these results that donor NK cells play an insignificant role in engraftment as well as in the afferent phase of GVHD, but may be important in immunosurveillance when murine bone marrow is transplanted across the major histocompatibility barrier. PMID- 2897143 TI - [Ocular changes in hemorrhagic fever with renal syndrome]. PMID- 2897144 TI - [Methods and criteria for evaluating overstrain in flight personnel]. PMID- 2897145 TI - Gamma-glutamyltransferase as a potential surrogate marker for detection of the non-A, non-B carrier state. AB - Alanine aminotransferase (ALT) is currently widely used as a surrogate marker for detection of blood having a higher risk of transmission of non-A, non-B hepatitis (NANBH). Studies in the chimpanzee model, in which the NANBH carrier state is well defined, have revealed gamma-glutamyltransferase to be considerably more sensitive for the detection of NANBH carrier blood. Further study is required to determine whether this marker is also more sensitive for detection of the chronic NANBH carrier state in man. PMID- 2897147 TI - Early X-irradiation of rats. 3. Survival of dopaminergic periglomerular cells of the olfactory blub. PMID- 2897146 TI - [Effectiveness of using cultured antigens for the serodiagnosis of hemorrhagic fever with renal syndrome by the immunofluorescence method]. AB - Clinical serological studies of hemorrhagic fever with renal syndrome (HFRS) demonstrated high effectiveness of indirect immunofluorescence procedure (IF) for serodiagnosis of this infection. The use of HFRS virus-infected VERO-E6 cells as the antigen for IF enhanced the sensitivity and specificity of the method as compared with the use of cryostatic sections of the lung tissue from wild rodents spontaneously infected with HFRS virus as the antigen. A technology for preparation of a polyvalent HFRS diagnosticum containing the antigens of two virus serotypes has been developed for serological diagnosis of HFRS in the European foci where the serological evidence of circulation of strains of serotypes 1 and 2 of HFRS virus pathogenic for man has been obtained. The specificity and sensitivity of detection of antibody to HFRS virus serotypes 1 and 2 by IF test using the polyvalent diagnosticum is equal to that in tests using individually tissue culture antigens of HFRS virus serotypes 1 and 2. It was found that in the patients' native sera antibodies of the IgM class are masked by antibodies of the IgG fraction, therefore the use of IF technique for detection of IgM antibody to HFRS virus aimed at early serological diagnosis of this infection is not effective. PMID- 2897148 TI - Recovery characteristics following antagonism of vecuronium with edrophonium, neostigmine or pyridostigmine. PMID- 2897149 TI - The pharmacokinetics and clinical effects of a low dose of alfentanil in elderly patients. AB - Alfentanil is a potent short-acting opioid analgesic which depresses respiration and can cause cardiovascular depression. The elderly can show greater sensitivity to opioid drugs which may be related to pharmacokinetic differences. The pharmacokinetics and clinical effects of alfentanil were studied in 10 elderly patients aged 68-86 years who were undergoing cystoscopy or urethrotomy under general anesthesia. After induction with thiopentone, and while the patient was breathing nitrous oxide with halothane 0.5% (enflurane 1.0% was given to one patient), a dose of alfentanil 4 micrograms/kg was given 15, 20, 30, 45 and 60 minutes after the alfentanil administration, and then every 30 minutes for 6 hours. Pulse rate (PR), systolic blood pressure (SBP), and minute volume (MV, calculated from the respiratory rate and the tidal volume) were measured at 1, 3, 5, 7 and 9 minutes after the alfentanil injection. Pharmacokinetic analysis showed Vc 82 (+/- S.D. 26) ml/kg; VDSS 277 (+/- S.D. 71) ml/kg; clearance 2.01 (+/- S.D. 0.64) ml/kg/min; t1/2 beta 117 (+/- S.D. 24) min. Comparison of these results with the results of other studies supports the view that older patients eliminate alfentanil less rapidly than younger patients, with prolongation of t1/2 beta and decreased clearance. The clinical results showed a decrease in minute volume from a mean value of 5944 ml before alfentanil to 1240 ml 1 minute after alfentanil (P less than 0.001). The minute volume was still significantly lower at 3 and 5 minutes, but had returned to the pre-alfentanil value by 7 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897150 TI - Clinical assessment of neuromuscular blockade produced by vecuronium using twitch, train of four, tetanus and post-tetanic twitch responses of the adductor pollicis muscle. AB - In the present investigation, the phenomenon of post-tetanic twitch potentiation (PTP) has been used to provide a sensitive index for neuromuscular blockade during an intense paralysis of the adductor pollicis muscle in man. We have also used and compared PTP assessment with that of twitch, train of four and tetanus in the same muscle and in the absence and presence of vecuronium (50 micrograms.kg-1). Vecuronium had a rapid onset of blockade (5-10s) and an intermediate duration of action (22-26 min). During the onset of blockade, the PTP response was still remaining (residual) whereas all the other mechanical responses disappeared within 2.5 min (Fig. 1b, c, d). Thus, the PTP values increased (upto 300% of control value of 18%, Fig. 1a) with increasing the intensity of neuromuscular blockade. The PTP value provided a better index for assessing the degree of neuromuscular blockade than did the twitch, train of four or the tetanus. However, during the onset of blockade, the PTP technique can also delay the onset of blockade, i.e. it has a decurarizing effect (Fig. 1b, c, d). During recovery of neuromuscular blockade, the PTP is actively involved in the enhancement of spontaneous recovery process, i.e. enhancement of de-curarization with repetitive stimulation of the ulnar nerve. In this respect, the PTP response recovers first, followed by the tetanus, train of four and the twitch responses. Thus the latter may be considered as a more sensitive index for the recovery process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897151 TI - [Beta-adrenergic receptor blocking action of methylflavonolamine hydrochloride]. PMID- 2897152 TI - [Progress in studies of the pharmacology of l-tetrahydropalmatine and l stepholidine]. PMID- 2897153 TI - Differential effects on gastrointestinal activity after intrathecal morphine, sufentanil and alfentanil in rats. PMID- 2897155 TI - Ipecac. When prevention fails. PMID- 2897156 TI - The case for ipecac syrup. PMID- 2897154 TI - Recent research into dementia. AB - In this paper, recent advances in the understanding of Alzheimer's disease that are relevant to the practising physician are reviewed, and an attempt is made to give researchers into Alzheimer's disease an overview into research areas other than their own. The fields covered include clinical presentation and investigation, neurochemistry, neuropathological abnormalities, immunological and viral aspects of aetiology and approaches to treatment. PMID- 2897157 TI - Pilot evaluation of instructing parents of newborns about poison prevention strategies. AB - Providing new parents with both written and verbal information about poisons and with syrup of ipecac appeared to be successful when distributed at discharge of their normal newborns. New parents who received neither information nor ipecac served as controls. Distribution occurred during a nine-month period, which was followed after an interval of three months by a four-month evaluation period. The average (+/- SD) time between infant poison exposures and parent telephone calls to the statewide poison center during the evaluation period was 5 +/- 3 minutes for the subjects and 12 +/- 4 for age-matched and socioeconomically matched controls. Both groups had similar frequencies of potentially dangerous exposures for which syrup of ipecac was recommended. Subject parents appeared to have homes which in various respects were significantly more child-safe than those of the controls. Significantly more control homes contained syrup of ipecac after the exposures than before (77% vs 41%). PMID- 2897158 TI - Intentional ipecac poisoning in children. AB - Ipecac (emetine) is a safe emetic for emergency home use. Its ready availability also provides the potential for child abuse and chronic self-induced emesis. The chronic administration of Ipecac can result in unusual symptom complexes such as chronic diarrhea and vomiting, muscle weakness, colitis, cardiomyopathy, fever, edema, or electrolyte disturbances. We describe patients who were intentionally poisoned and who demonstrated these symptoms. Because of the widespread use of ipecac for therapy in acute accidental poisonings, toxicology laboratories may not look for or report the presence of this drug in their routine screens. This may delay the recognition of chronic ipecac poisoning in patients. PMID- 2897159 TI - Syrup of ipecac. The case for distribution from physicians' offices. AB - Data from a nationally representative sample of household interviews were analyzed to examine public preparedness for childhood poisoning episodes. Eighty eight percent (61% to 77% in nonwhite groups) of respondents from households with children younger than 10 years had heard of poison control centers and 70% (50% to 57% in nonwhites) stated that they had the telephone number of such a center. In contrast only 25% stated they had syrup of ipecac in their home. Among blacks and Hispanics this proportion was 9%. To explore possible reasons for this we telephoned a sample of 65 physicians listed in the greater Washington, DC, telephone directory as providers of care for infants and children. Of the 45 (69%) who agreed to be interviewed, 73% informed their patients about poison control centers and 53% provided the appropriate telephone number. Although 78% believed parents should have ipecac in the house, only three (7%) of 45 actually dispensed ipecac to parents. We conclude that ipecac is not widely available in the homes of American children. By regularly dispensing it in the course of pediatric care, physicians could largely remedy this deficiency. PMID- 2897160 TI - Mapping of human methylmalonyl CoA mutase (MUT) locus on chromosome 6. AB - Methylmalonyl CoA mutase (MCM) catalyzes an essential step in the degradation of several branch-chain amino acids and odd-chain fatty acids. Deficiency of this apoenzyme causes the mut form of methylmalonic acidemia, an often fatal disorder of organic acid metabolism. An MCM cDNA has recently been obtained from human liver cDNA libraries. This clone has been used as a probe to determine the chromosomal location of the MCM gene and MUT locus. Southern blot analysis of DNA from human-hamster somatic-cell hybrid cell lines assigned the locus to region q12-p23 of chromosome 6. In situ hybridization further localized the locus to the region 6p12-21.2. A highly informative RFLP was identified at the MCM gene locus which will be useful for genetic diagnostic and linkage studies. PMID- 2897162 TI - RFLP of the X chromosome-linked glucose-6-phosphate dehydrogenase locus in blacks. AB - The X chromosome-linked glucose-6-phosphate dehydrogenase (G6PD) A(+) variant is found in approximately 20% of blacks. Examination of the structure of the G6PD A(+) gene revealed that AT----GC transition occurred in the variant gene, resulting in the amino acid substitution Asn----Asp at the one hundred forty second position from the NH2-terminal of the enzyme (Takizawa and Yoshida 1987). The nucleotide change created an additional FokI cleavage site in the variant A(+) gene; thus, the FokI fragment type of the variant A(+) DNA differs from that of the normal B(+) DNA. PvuII fragment type is also found to be polymorphic in blacks, but not in Caucasians. The majority of blacks, as well all nonblacks, have a major hybridization-positive fragment of approximately 4.0 kbp (PvuII type 1), while approximately 20% of blacks have a major fragment of approximately 1.5 kbp (PvuII type 2). The G6PD gene with PvuII type 2 contains an additional PvuII cleavage site approximately 0.7 kbp downstream from the mutation site of the G6PD A(+). Approximately 40% of the G6PD A(+) genes have PvuII type 2, while only approximately 10% of the G6PD B(+) genes are associated with PvuII type 2. The data indicate a statistically significant (X2 = 6.85, P less than .020) linkage disequilibrium between the G6PD types and the PvuII types at the G6PD locus. PMID- 2897161 TI - Isolation and analysis of DNA markers specific to human chromosome 15. AB - Chromosome-specific DNA markers provide a powerful approach for studying complex problems in human genetics and offer an opportunity to begin understanding the human genome at the molecular level. The approach described here for isolating and characterizing DNA markers specific to human chromosome 15 involved construction of a partial chromosome-15 phage library from a human/Chinese hamster cell hybrid with a single human chromosome 15. Restriction fragments that identified unique- and low-copy loci on chromosome 15 were isolated from the phage inserts. These fragments were regionally mapped to the chromosome by three methods, including Southern analysis with a mapping panel of cell hybrids, in situ hybridization to metaphase chromosomes, and quantitative hybridization or dosage analysis. A total of 42 restriction fragments of unique- and low-copy sequences were identified in 14 phage. The majority of the fragments that have been characterized so far exhibited the hybridization pattern of a unique locus on chromosome 15. Regional mapping assigned these markers to specific locations on chromosome 15, including q24-25, q21-23, q13-14, q11-12, and q11. RFLP analysis revealed that several markers displayed polymorphisms at frequencies useful for genetic linkage analysis. The markers mapped to the proximal long arm of chromosome 15 are particularly valuable for the molecular analysis of Prader Willi syndrome, which maps to this region. Polymorphic markers in this region may also be useful for definitively establishing linkage with one form of dyslexia. DNA probes in this chromosomal region should facilitate molecular structural analysis for elucidation of the nature of instability in this region, which is frequently associated with chromosomal aberrations. PMID- 2897164 TI - Visual compatibility of esmolol hydrochloride and various injectable drugs during simulated Y-site injection. PMID- 2897163 TI - Extensive DNA polymorphism at the factor XIIIa (F13A) locus and linkage to HLA. AB - A 1,161-bp EcoRI fragment from the 5' end of the cDNA coding for human factor XIIIa (gene symbol F13A) was used to identify RFLPs in human DNAs. Several different RFLPs were identified with 15 different restriction enzymes. Two RFLPs detected with the restriction enzyme BamHI and one multiallelic RFLP detected with BclI were used for further studies. Linkage relationships between these three polymorphisms and the HLA complex were studied in DNA samples from the 40 Centre d'Etude du Polymorphisme Humain families. Combining all of the data to form highly informative haplotypes, we found linkage to HLA with a maximum lod score of 11.44 at a recombination fraction of .25 for males and .35 for females. These three RFLPs at the FXIIIa locus provide a highly informative marker for the short arm of chromosome 6 with an observed heterozygosity of 91%. Using this marker and the HLA locus, one can confirm or exclude the assignment of gene loci to most of chromosome 6p. PMID- 2897165 TI - An HLA-D region restriction fragment associated with refractory Behcet's disease. AB - We examined the association between HLA-DQ and refractory Behcet's disease at the genomic DNA level. Using a restriction endonuclease Taq I and a DQ beta cDNA probe, we identified the 1.9 kb DQ beta restriction endonuclease fragment tightly associated with refractory Behcet's disease. This observation indicates that genomic HLA-DQ variations affect the development of refractory Behcet's disease. PMID- 2897166 TI - Adjunctive alprazolam for schizophrenia with panic anxiety: clinical observation and pathogenetic implications. AB - Seven patients with schizophrenia and panic attacks all showed marked improvement of positive and negative schizophrenic symptoms when alprazolam was openly added to antipsychotic medication. Panic attacks may identify alprazolam-responsive schizophrenic patients and may define a distinct pathophysiologic subgroup. PMID- 2897167 TI - Dosing practices for high- and low-potency neuroleptics. PMID- 2897168 TI - [Treatment of male infertility with the preparation tamoxifen]. PMID- 2897170 TI - Surface-enhanced Raman spectroscopy of the catecholamine neurotransmitters and related compounds. PMID- 2897169 TI - A case of juvenile metachromatic leukodystrophy--the third case in Japan. AB - We report here a case of juvenile metachromatic leukodystrophy. The patient is an 8-year-old boy with motor and mental deterioration, which began at about age 3. He has also suffered from astatic seizures since age 8. Arylsulfatase A activity in the patient was markedly decreased in peripheral leukocytes, cultured fibroblasts and urine. Sulfatide was detected in urine from the patient by thin layer chromatography. Peripheral motor and sensory nerve conduction velocities were markedly reduced. Computerized tomography of the brain showed low density areas in the periventricular white matter which were not enhanced by intravenous contrast material. His parents' arylsulfatase A activities were about half those of normal controls. This is the third case of juvenile metachromatic leukodystrophy in Japan. PMID- 2897171 TI - [Results of cryptorchism therapy. A study of 232 patients]. AB - 232 patients had been treated for cryptorchidism. The disorder was unilateral in 126, bilateral in 106 patients. Therapy was performed either with human chorionic gonadotropin in 102 cases (hCG total dose of 18.000 I.U.) or surgery in 129 cases. Testicular descent was achieved in 51.5% by hormonal therapy and in 51.9% by surgery. Unilateral cases were subject to successful treatment in 53.2%, bilateral cases in 50%. The influence of initial finding (inguinal vs. abdominal retention) and age of the patients on results were analysed. Inguinal retention (n = 240) was successfully treated in 50.8%, abdominal retention (n = 94) in 54.3%. Testicular descent after therapy was found in 52.9% for patients 2-9 years of age (n = 119), in 50% for patients 10-13 yrs. of age (n = 88) and in 48% for patients older than 13 (n = 25). Regular findings after therapy was noted in 51.7% of all 232 patients. Method of therapy, initial finding and patients age, however, could not be shown to influence results significantly. PMID- 2897172 TI - Pre-induction of anesthesia in pediatric patients with nasally administered sufentanil. AB - To evaluate nasally administered sufentanil, 1.5-4.5 micrograms/kg, for pre induction (i.e., pre-medication/induction) of anesthesia in pediatric patients, the authors studied ASA PS 1 or 2 patients scheduled for elective surgery. Eighty children, ages 6 months to 7 yr, were randomized to receive sufentanil (1.5, 3.0, or 4.5 micrograms/kg) or placebo (normal saline, 0.03 ml/kg) nasally over 15-20 s. Induction of anesthesia was completed with 5% halothane and O2 via facemask. After tracheal intubation, anesthesia was maintained with N2O (60-70%) and halothane, as clinically indicated. A blinded observer remained with the child from prior to drug administration until discharge from the recovery room. Patients given sufentanil were more likely to separate willingly from their parents and be judged as calm at or before 10 min compared to those given saline. Ventilatory compliance during induction of anesthesia decreased markedly in 25% of subjects given sufentanil, 4.5 micrograms/kg. Subjects given sufentanil moved or coughed less during tracheal intubation and required less halothane compared to those given placebo. During recovery, patients given sufentanil cried less and fewer needed analgesics; recovery times were similar for all groups. However, patients given sufentanil, 4.5 micrograms/kg, had a higher incidence of vomiting in the recovery room and during the first postoperative day. The authors conclude that nasally administered sufentanil, 1.5 or 3.0 micrograms/kg, facilitates separation of children from parents, has minimal side effects, may improve intubating conditions, and can provide postoperative analgesia. PMID- 2897173 TI - Does chronic treatment with calcium entry blocking drugs reduce perioperative myocardial ischemia? AB - To examine the role of chronic calcium entry blocking drug administration on perioperative myocardial ischemia and, specifically, the frequency of hemodynamically unrelated ischemia, the authors studied 444 patients undergoing coronary artery bypass operations. Before induction of anesthesia, 119 patients who chronically took calcium entry blocking drugs received nifedipine 20 mg or diltiazem 60 mg orally, 74 received calcium entry and beta adrenergic blocking drugs, 71 received beta blocking drugs only, and 180 received neither. New ischemia occurred in 208 (46.8%) patients; 55 at arrival to the operating room, 86 only after induction, and 67 separately during both periods. Two-thirds of all ischemia was not related to extremes of heart rate or blood pressure; this type was not less frequent in patients receiving calcium entry blocking drugs. Ischemia did occur less frequently in the two patient groups receiving beta adrenergic blocking drugs (34% vs. 53%), a result of less tachycardia both on arrival (3.4% vs. 15.4%) and during anesthesia, when peak heart rate exceeded 109 bpm in only one of 145 beta-blocked patients compared to 29 of 299 not receiving beta blocking drugs. While ischemia appeared during anesthesia in 34.5% of all patients, its incidence was doubled (63%) when heart rate was greater than or equal to 110 bpm. At lower heart rates, the incidence of ischemia did not differ among groups. With respect to all types of ischemia, patients receiving calcium entry blocking drugs only were indistinguishable from those receiving no antianginal therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897174 TI - Anesthetic and hemodynamic effects of the alpha 2-adrenergic agonist, azepexole, in isoflurane-anesthetized dogs. AB - The authors studied the reduction in anesthetic requirement (MAC) and the hemodynamic effects of the highly selective alpha 2-adrenergic agonist azepexole in isoflurane-anesthetized dogs. Eleven male beagles were anesthetized with isoflurane in oxygen. After a 2-h equilibration period, they determined isoflurane MAC and baseline hemodynamic function. Azepexole (at 0.1, 0.3, and 1.0 mg/kg) was administered via a right atrial port over 15 min, while each dog was given isoflurane at the MAC dose for that animal. Twenty minutes after the end of infusion, at a time when hemodynamic variables were stable, they reassessed hemodynamic function. They then determined isoflurane MAC again. In other experiments, dogs were pretreated with either idazoxan (the alpha 2-adrenergic antagonist; n = 5) or naloxone (the opiate antagonist; n = 7) prior to the administration of azepexole. Isoflurane MAC was determined before and after each dose of azepexole. Isoflurane MAC decreased as the dose of azepexole increased, to the extent that at the highest dose (1 mg/kg) the decrement in MAC was more than 85%. This reduction of MAC caused by azepexole could be completely prevented by pretreatment with idazoxan, while naloxone was without effect. Azepexole did not change mean arterial blood pressure, but caused heart rate and cardiac output to progressively decrease. The MAC-reducing effect of azepexole appears to be mediated by alpha 2 adrenoreceptors. Given the extent of the reduction of MAC, it is unlikely that inhibition of central noradrenergic neurotransmission through agonism of presynaptic alpha 2 adrenoreceptors is the sole explanation, since complete disruption of central noradrenergic tracts decreases MAC by only 40%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897175 TI - Intrathecal somatostatin in rats: antinociception only in the presence of toxic effects. AB - Effects of intrathecal (i.t.) somatostatin (SST) (10, 30, and 100 micrograms) on nociception, and autonomic and motor function were evaluated in rats with chronically implanted lumbar i.t. catheters. Doses of 10 and 30 micrograms SST i.t. had no effect on thermal cutaneous nociception, (hot plate and tail flick response). Thirty micrograms SST i.t. did not effect the visceral chemical evoked nociception (acetic acid writhing test) as compared to saline control groups. Rats treated with 100 micrograms SST i.t. invariably showed temporary or permanent hindlimb motor dysfunction, with flaccid paralysis in the most severe cases (motor function tests, electromyographic response). Blockade of the tail flick and foot pinch response was observed to a variable degree, and only in the presence of detectable motor impairment. Out of 40 animals injected with 100 micrograms SST i.t., 25% died within 10 min following injection. Effects of SST on the volume evoked micturition reflex were assessed in rats with chronically implanted bladder catheters. Three of the nine surviving animals receiving 30 micrograms SST i.t. and all animals receiving an additional dose of 60 micrograms SST i.t. showed a complete block of the micturition reflex and subsequent development of an overflow bladder. Histological examination of spinal cords revealed a mild inflammatory response in four out of five animals treated with 30 micrograms SST i.t. In spinal cords of animals, which had received 100 micrograms SST i.t. (n = 4), mild or severe nucleolysis of ventral and dorsal horns in the presence of inflammatory reaction was observed. Present experiments clearly demonstrate highly toxic effects of SST in rats with no margin of safety between antinociception and motor dysfunction. PMID- 2897176 TI - Vecuronium in alcoholic liver disease: a pharmacokinetic and pharmacodynamic analysis. AB - To determine the effect of alcoholic liver disease on the pharmacokinetics and pharmacodynamics of vecuronium, the authors administered vecuronium 0.1 mg.kg-1 iv to ten surgical patients with alcoholic liver disease and ten healthy surgical patients. All patients were anesthetized with nitrous oxide and isoflurane. We recorded and quantitated the force of thumb adduction in response to supramaximal ulnar nerve stimulation. Plasma concentrations of vecuronium and its 3-desacetyl metabolite were determined by a capillary gas chromatography assay. Only the time to attain 100% twitch depression (onset time) was prolonged in liver disease patients (2.8 +/- 0.7 min; mean +/- SD) as compared to control patients (1.9 +/- 0.4 min). The time from vecuronium administration to recovery of twitch tension was unaffected by alcoholic liver disease. The time to the reappearance of twitch response was 32.7 +/- 9.7 min in patients with liver disease and 36.8 +/- 15.5 min in controls. Plasma concentration-time data were fit to a two-compartment model. Vecuronium clearance, steady-state volume of distribution, and elimination half-time were unchanged by alcoholic liver disease. The authors conclude that alcoholic liver disease does not affect the pharmacokinetics or duration of action of vecuronium when an intravenous bolus dose of 0.1 mg.kg-1 is administered. PMID- 2897178 TI - Rectal bloody diarrhea in an 18-month-old male. PMID- 2897177 TI - Update on AIDS--new video cassette. PMID- 2897179 TI - Comparative trials including a beta 2 adrenergic agonist, a methylxanthine, and a mast cell stabilizer. PMID- 2897180 TI - As I see it. Don't skip keynote or coffee sessions. PMID- 2897181 TI - Pentasa in lieu of sulfasalazine. PMID- 2897182 TI - [Vasculitis in rheumatoid polyarthritis and periarteritis nodosa]. PMID- 2897183 TI - [Takayasu's disease of abdominal form with renovascular hypertension: apropos of a case]. PMID- 2897184 TI - [Association of Horton's disease and periarteritis nodosa: fortuitous association or a borderline form of the same disease?]. PMID- 2897185 TI - Pilin independent binding of Neisseria gonorrhoeae to immobilized glycolipids. AB - The adherence process in pathogenesis involves the attachment of bacteria to structures present on eukaryotic cell surfaces. To investigate components necessary for this interaction, we have characterized the binding of N. gonorrhoeae to eukaryotic glycolipids immobilized on thin layer chromatograms. The gonococci specifically bind to a subset of glycolipids consisting of lactosylceramide, gangliotriosylceramide, and gangliotetraosylceramide. This binding was identified in both piliated and nonpiliated cells, and is postulated to be mediated by a nonpilin lectin-like adhesin protein. PMID- 2897186 TI - Molecular principles of antigenic variation in Neisseria gonorrhoeae. AB - The genome of Neisseria gonorrhoeae harbours many gene loci for the production of variant pili. Strain MS11 has two expression genes (pilE) with promoter and complete coding sequences. The remaining genes are silent (pilS) lacking the promoter and the conservative amino terminals coding sequences of pilin. The pilus genes consist of six variable minicassettes (mc's), that are flancked by strictly conserved sequences. Upon phase (P+ to P+) and antigenic (P+ to P-, or vice versa) transitions minicassettes from silent loci are transferred from silent pilus gene copies to the expression gene by gene conversion. P- variants resulting from such rearrangements still produce pilin mRNA as well as pilin, but only a few are found on the surface of those gonococci. PMID- 2897187 TI - Gene conversion accounts for pilin structural changes and for reversible piliation "phase" changes in gonococci. AB - Pilus+ "wild-type" gonococci (Gc) frequently display gene conversion of their expressed complete pilin gene (CPG); a copy of DNA derived from one of the Gc genome's multiple silent partial pilin genes (PPG) is recombinationally-inserted into the CPG's central and 3' portions with formation of a new, chimeric CPG. Expression of that new CPG leads to either 1) retention of pilus+ phenotype but change in pilin primary structure/antigenicity, or 2) phase change to pilus- phenotype capable of reverting. This study utilizes pilus revertants of P-rp +/- Gc and P+ colony morphotype variants spawned by P++ Gc to examine pilin gene conversion in strain MS11mk Gc in greater detail. Each revertant's and variant's expressed pilin gene's sequence (as pilin mRNA) was defined to learn whether their differences are due to gene conversion by different PPGs, or by varying stretches from the same PPG, or both. Gene conversion by PPG pilS1 copy 2 has been documented in Gc recovered from a human volunteer's urethra previously inoculated with pilus Gc (strain MS11). The pilus+ Gc isolated expressed structurally/antigenically distinct pilins. PMID- 2897188 TI - Three dimensional structure of bacterial pili. AB - Crystallographic and associated biochemical and structural studies are in progress on the fiber-forming pilin proteins of the gonococcal pilus. Preparative scale purification procedures have been developed for the gonococcal pilin protein, which appear generally applicable to bacterial pilins. For three gonococcal pilin protein strains, we have obtained both reassembled pilus fibers and three-dimensional crystals. One needle-shaped crystal form of gonococcal C30 pilin diffracts beyond 3 A resolution using synchrotron x-ray radiation. A diffraction data set to 3.5 A resolution has been collected on these needle shaped crystals (lattice spacings a = 125.4(3) b = 120.4(3), c = 26.61(4) A) in which the packing arrangement of the pilin subunits appears to resemble that seen in the pilus fibers using electron microscopy. X-ray diffraction data confirm our proposed model for the overall polypeptide fold of a pilin subunit, which is an antiparallel 4-alpha helix bundle similar to tobacco mosaic virus coat protein and myohemerythrin. PMID- 2897189 TI - Restriction site polymorphism in genes encoding type 2 but not type 1 gonococcal IgA1 proteases. AB - Neisseria gonorrhoeae produces two phenotypically distinct types of IgA1 proteases, each of which cleaves a specific peptide bond in the hinge region of the human IgA1 heavy chain. The genes encoding IgA1 protease from twenty-eight different strains of N. gonorrhoeae, including twelve which produce type 1 enzyme, thirteen which produce type 2 enzyme, and three which are protease negative, were analyzed. Nine restriction site patterns were found in the iga genes. All twelve type 1 strains showed identical restriction maps of the iga gene, which differed from all the iga-2 variants. The three protease negative strains each contained DNA homologous to the probe. While strain to strain variation in restriction maps of specific genes is not unique and has been reported in N. gonorrhoeae previously, the existence of such restriction site polymorphism among iga-2 genes contrasts strongly with the lack of such variation among iga-1 genes. The basis for this lack of diversity among the iga-1 genes is under further investigation. PMID- 2897190 TI - Intraventricular somatostatin-14, arginine vasopressin, and oxytocin: analgesic effect in a patient with intractable cancer pain. AB - The analgesic effect of intraventricular somatostatin-14 (SOM-14), arginine vasopressin (AVP), and oxytocin (OT) were tested in one terminally ill cancer patient with a diffuse mesothelioma suffering intractable continuous and incapacitating thoracic pain. SOM-14 reduced pain by 90% for 48 min; AVP reduced pain by 95% for 75 min, and OT reduced pain by 88% for 77 min. The only notable side effects were seen after the administration of AVP, which induced anesthesia and flaccid paralysis of the lower limbs, from which the patient fully recovered after 20 h. PMID- 2897191 TI - Potential histamine H2-receptor antagonists: analogues of classical antagonists containing 4-substituted-3-aminofurazan moieties. PMID- 2897192 TI - Restriction fragment length polymorphism analysis of mutated transthyretin in vitreous amyloidosis. AB - Amyloid deposits of the vitreous are usually associated with familial amyloidotic polyneuropathy (FAP). Various mutated forms of transthyretin (prealbumin) seem to form the main amyloid fibril component. Five Swedish patients, all with vitreous amyloidosis but no systemic symptoms or family history of amyloidosis, were examined using restriction fragment length polymorphism analysis. Genomic DNA was tested with a transthyretin complementary DNA probe. After cleavage with Nsi1, two restriction fragment length polymorphism markers of 5.1 and 1.5 kilobase were detected in the patients but not in the control subjects. These observations indicate the same methionine for valine substitution at position 30 of the transthyretin molecule in patients with vitreous amyloidosis as seen in Swedish patients with FAP as well as in patients with FAP from Japan and Portugal, and patients of Swedish descent with FAP from the United States. PMID- 2897193 TI - Assessing dementia. PMID- 2897194 TI - Imaginal desensitization: a cost-effective treatment in two shop-lifters and a binge-eater resistant to previous therapy. AB - Case reports are given of three patients, two suffering from compulsive shop lifting and one from binge-eating, who responded to a week's treatment with imaginal desensitization after having failed to respond to prolonged interpretative psychotherapy. Expectancy of improvement did not appear to play a major role in their response, but it appears impossible to disprove that expectancy determines the response to this or any form of psychotherapy. Whether or not imaginal desensitization acted specifically in the present study, in view of its cost-efficacy it is suggested it is worthy of trial in impulse disorders which have persisted despite treatment. PMID- 2897196 TI - General pharmacology of 1-(2-ethoxyethyl)-2-(4-methyl-1 homopiperazinyl)benzimidazole difumarate. 2nd communication: Effects on the circulation and the other systems. AB - Effects of 1-(2-ethoxyethyl)-2(4-methyl-1-homopiperazinyl)benzimidazole difumarate (KB-2413) on the circulation and the other systems were compared with those of ketotifen and chlorpheniramine. 1. Among the effects on the circulation and the respiratory system, KB-2413 as well as ketotifen and chlorpheniramine transiently inhibited respiration at 3 mg/kg i.v. and slightly decreased blood pressure in dogs. KB-2413 slightly decreased heart rate in dogs, but ketotifen slightly increased it. 2. KB-2413 at 100 mg/kg p.o. slightly decreased the volume of gastric juice in rats and dose-dependently increased biliary secretion in rats in the dose range of 10-100 mg/kg i.d. On the other hand, ketotifen and chlorpheniramine decreased biliary secretion. 3. KB-2413 inhibited the spontaneous movements of various isolated smooth muscles at a high concentration of 10(-4) g/ml. 4. The autonomic system in cats and the motor nervous system in rats were not influenced by KB-2413 at 3 mg/kg i.v. 5. The blood clotting system, blood sugar level, urine volume and urinary electrolytes in rats were not affected by KB-2413 in the dose range of 10-100 mg/kg p.o. 6. KB-2413 inhibited carrageenin-induced rat paw edema at 100 mg/kg p.o. In conclusion, KB-2413 showed a less potent effect on the circulation and the other systems than ketotifen and chlorpheniramine, and no results suggested serious side effects of KB-2413. PMID- 2897195 TI - Purification of the glutamine synthetase II isozyme of Drosophila melanogaster and structural and functional comparison of glutamine synthetases I and II. AB - Glutamine synthetase II was purified from Drosophila melanogaster adults. It was completely separable from the isozyme glutamine synthetase I by means of DEAE chromatography. The complete enzyme has an apparent molecular weight of 360,000. After two-dimensional electrophoresis it gave a single molecular species with an apparent molecular weight of 42,000. Structural analysis of the two isozymes showed that they are different both in subunit molecular weight and in isoelectric point. Peptide maps of the purified subunits showed considerable dissimilarity. Glutamine synthetase II is more active than glutamine synthetase I in the transferase assay, while the opposite is true in the biosynthetic assay. The kinetic parameters were determined, showing again noteworthy differences between the two isozymes. We therefore conclude that two forms of glutamine synthetase are present in Drosophila, with different primary structures, different kinetic behavior, and the possibility of different functional properties. PMID- 2897197 TI - Antiallergic effects of the new histamine H1-receptor antagonist tazifylline in healthy atopic and non-atopic subjects. AB - Single oral doses (5, 10 and 15 mg) of the new H1-receptor antagonist 3,7-dihydro 7-[2-hydroxy-3-[4-[3-phenylthio) propyl]-1-piperazinyl]propyl-1,3-dimethyl-1H purine-2,6-dione dihydrochloride (tazifylline, RS-49014) were administered at 7 day intervals to 12 atopic and 12 non-atopic volunteers in a double-blind randomised cross-over study. Antiallergic activity was evaluated from pre to 60 min post dose inhibitions of wheal and flare areas provoked by various cutaneous challenges. Atopic subjects showed greater skin reactivity than non-atopics to some challenges. Tazifylline was associated (in atopics and non-atopics) with statistically significant dose related inhibitions, of flare over 5-15 mg and of wheal (10-15 mg) induced by the more potent and reproducible challenges of codeine, 1% histamine and anti-IgE. Antiallergic activity of tazifylline in the 10-15 mg dose range was superior to 5 mg without the intervention of clinically significant sedative effects at any of the 3 dose levels tested. PMID- 2897198 TI - Abnormal amino-acid concentrations in the blood of patients with acquired immunodeficiency syndrome (AIDS) may contribute to the immunological defect. AB - The acquired immunodeficiency syndrome (AIDS) is accompanied by a metabolic disturbance. Serum samples from persons with antibodies against the AIDS associated human immunodeficiency virus (HIV/LAV/HTLV III) including persons without overt symptoms, patients with lymphadenopathy syndrome (LAS) and patients with AIDS or AIDS-related complex (ARC) contain on the average significantly elevated concentrations of arginine and glutamate. The serum from patients with overt AIDS contains also, on the average, significantly reduced concentrations of methionine and cystine. In vitro experiments revealed that the [3H]thymidine incorporation by mitogenically stimulated murine lymphocytes and cloned T cells is inhibited by an elevation of the extracellular glutamate concentration and augmented by the addition of cysteine. This suggests the possibility that the abnormal concentrations of glutamate and cystine in the blood of HIV-infected persons may contribute to the defect in the lymphoid system. PMID- 2897199 TI - Nephrectomy-induced alterations in the synthesis of catecholamines in the sympathetic nervous system and central nervous system. AB - Reduction in renal function is a key factor to the development of salt-dependent hypertension; however, the mechanism is obscure. To examine the role of the sympathetic nervous system (SNS) and central catecholaminergic neurons in this predisposition to the development of hypertension, the activity of tyrosine hydroxylase (TH) was determined in SNS and in several brain regions. In another group of unilaterally nephrectomized rabbits, cardiovascular responsiveness to norepinephrine was determined. A unilateral nephrectomy increased the activity of TH in the midmedulla, a brain region important in the baroreflex regulation of blood pressure, and in the adrenal gland, the major source of circulating catecholamines. The activity of TH was decreased in the pons-upper medulla region. No alterations were found in the proximal and distal mesenteric arteries, lower medulla, midbrain or hypothalamus. No alteration in blood pressure or cardiovascular responsiveness to norepinephrine was found. This study indicates that a unilateral nephrectomy produces long-lasting effects on central catecholaminergic neurons and the sympathetic nervous system without an effect on blood pressure or cardiovascular responsiveness. PMID- 2897200 TI - Do beta-blockers really increase peripheral vascular resistance? Review of the literature and new observations under basal conditions. AB - Most antihypertensive drugs act by counteracting vasoconstrictor mechanisms and lower blood pressure by lowering vascular resistance. The beta-blockers, which have the unique feature of counteracting cardiac sympathetic drive, seem to be a major exception to this generalization. Moreover, their degree of cardiodepression is not only directly correlated with the initial sympathetic tone, but also with their degree of intrinsic sympathicomimetic activity (ISA). Cardiodepression initially evokes a proportional rise in vascular resistance. As indicated by review of the literature, the antihypertensive effect of beta blockers always parallels a decline in vascular resistance. Minimizing cardiac sympathetic drive by strict bedrest and studying beta-blockers with different degrees of ISA in 50 hypertensive patients showed that initially the effect of the drugs is offset by a rise in vascular resistance proportional to the fall in cardiac output. After that, blood pressure always fell parallel with the decline in vascular resistance. In the long run blood pressure and vascular resistance were always positively correlated, whatever the level of cardiac output. Thus, like all other antihypertensive agents, beta-blockers also lower blood pressure through interference with a vasoconstrictor mechanism. PMID- 2897201 TI - DNA techniques in prenatal diagnosis and in genetic pathology. AB - New molecular techniques concerned with the isolation and identification of DNA fragments can be used for carrier detection and early prenatal diagnosis either by direct detection of the mutant DNA sequence or by indirect linkage studies employing RFLPs as DNA markers. Gene specific DNA probes are available already for a number of genetic disorders, such as the hemoglobinopathies, hemophilia A and B, alpha 1-antitrypsin deficiency, phenylketonuria, and chronic granulomatous disease. Coinheritance of DNA-polymorphisms can be traced, eg, for Norrie disease, myotonic dystrophy, Duchenne and Becker muscular dystrophies, and Huntington chorea. Several genes have been localized successfully to specific chromosome regions. By "walking" or "jumping" along the chromosome, it is hoped finally to reach further gene loci of interest, to analyze the molecular pathology of single gene disorders, and to find new ways for their prevention. PMID- 2897202 TI - Effect of aneuploidy and neoplasia on human ribosomal DNA inheritance. AB - A DNA length polymorphism in the nontranscribed spacer region of the repeating unit that codes for human ribosomal RNA produces a characteristic pattern or restriction fragments in each individual. Quantitative densitometric analysis of ribosomal ribosomal DNA fragment distribution in families demonstrates additive inheritance in those with chromosomally normal or aneuploid offspring. Differences between offspring and parental ribosomal DNA patterns could be explained by a heterogeneous distribution of length variants on the acrocentric chromosomes. New ribosomal DNA length variants of 9.0, 6.7, 5.5, and 5.2 kilobases were observed in normal individuals after BamHI restriction, and the former two were present in multiple copies. A panel of solid tumor specimens exhibited ribosomal DNA patterns that were generally characteristic of the patient rather than tumor type. However, novel ribosomal DNA length variants or changes in length variant proportions were noted in three of the four tumors for which adjacent normal tissue was available for comparison; these alterations occurred in a Burkitt lymphoma, a teratoma, and a Wilms tumor. A consistent karyotype of 50,XY in the Wilms tumor specimen supports previous evidence for increased repetitive DNA variation in aneuploid, neoplastic tissues. PMID- 2897203 TI - Molecular approaches to developmental genetics and pathology. AB - New insights into gene structure and expression and the observation that homeobox containing genes, the t-complex, and oncogenes are expressed also in humans contribute to the understanding of normal and pathobiological mechanisms of embryonal and fetal development. PMID- 2897204 TI - Effect of metabolic or respiratory acidosis on rabbit renal medullary proton ATPase. AB - Distal urinary acidification is thought to be mediated by an H+-ATPase sensitive to N-ethylmaleimide and dicyclohexyl-carbodiimide. We have studied the effect of chronic metabolic acidosis (NH4Cl for 3 days) or respiratory acidosis (inhalation of 10% CO2 for 2 days) on the H+-ATPase of plasma membranes prepared from the medulla. The enzymatic assay for the H+-ATPase was performed in the presence of ouabain and oligomycin and in the absence of Ca. H+-transport activity was assessed by the quenching of acridine orange in the presence of ATP. The 15-25% sucrose gradient fraction was enriched 40-fold in enzymatic activity over the homogenate, and 8-fold in enzymatic activity and 4-fold in H+-transport activity over the fluffy fraction (38,000 X g). Metabolic acidosis (pH less than 7.31) or chronic hypercapnia (PCO2 greater than 66 mmHg; 1 mmHg = 133.3 Pa) was induced for 2-3 days. Both groups showed the same enrichment factor in enzymatic and H+ transport assays as the control rabbits. Enzymatic and H+-transport activities, however, were not different between animals with respiratory acidosis and controls. Kinetic studies failed to disclose an increase in Vmax (673 vs. 702 mumol/(mg protein.min] or a decrease in Km (0.43 vs. 0.48 mM) in chronic hypercapnia as compared with controls. Metabolic acidosis also failed to increase H+-ATPase activity. These data demonstrate that the H+-ATPase of renal medulla does not display the expected increase in activity during acidosis. The role of this H+-ATPase in the adaptation to acidosis remains to be determined. PMID- 2897205 TI - In vitro cytotoxic effect of alpha-hemolytic Escherichia coli on human blood granulocytes. Correlation with size of alpha-hemolysin production. AB - The correlation of the in vitro cytotoxic effect of 107 alpha-hemolytic strains of Escherichia coli with various other bacterial characteristics was investigated. Damage to human blood granulocytes in the presence of fresh or heated autologous plasma was quantified by measuring the release of chromium-51 from labelled cells. 95 strains had a cytotoxic effect which was equal in the presence of fresh or heated plasma, whereas 12 strains showed an effect which was reduced in fresh compared with heated plasma. The cytotoxic effect increased as the number of bacteria per granulocyte was increased. The average size of the alpha-hemolysin production of the strains was 185 HU50/ml ranging from 3 2519HU50/ml. The cytotoxic effect of the strains was directly correlated with the size of the alpha-hemolysin production. The cytotoxic effect was not correlated with the O-antigen serotype or the type of infection from which the strains were derived. These results indicate that the ability to produce alpha-hemolysin is the bacterial characteristic which is of decisive importance for the cytotoxicity of alpha-hemolytic E. coli towards human blood granulocytes. PMID- 2897206 TI - Pharmacokinetic and pharmacodynamic properties of intravenous fenoldopam, a dopamine1-receptor agonist, in hypertensive patients. AB - 1 The pharmacokinetic properties of intravenous fenoldopam, a selective dopamine1 receptor agonist, were studied in 10 patients with essential hypertension. 2 Reduction in blood pressure was linearly related to the log fenoldopam plasma concentration (r = 0.69) and the log fenoldopam infusion rate (r = 0.71). 3 The mean elimination half-life (+/- s. e. mean) was 9.8 +/- 1.0 min. The total body clearance was 30.3 +/- 2.3 ml kg-1 min-1 and the volume of distribution was 582 +/- 62 ml kg-1. 4 The rapid onset of action, short elimination half-life, linear dose-response relationship, and ease of administration suggest that fenoldopam may have a role where parenteral treatment of hypertension is required. PMID- 2897207 TI - Beta-mimetics in preterm labour: an overview of the randomized controlled trials. AB - Controversy continues about the use of beta-mimetic drugs in preterm labour. One reason for this is that the adequately controlled trials of these drugs have all been small and have thus provided very imprecise estimates of their effects. We have therefore conducted a 'meta-analysis' using data relating to 890 women who participated in the 16 methodologically acceptable controlled trials of these agents in the treatment of preterm labour. This analysis demonstrates an unequivocal effect of beta-mimetic tocolytic administration in delaying delivery, and this is reflected in a reduction in the frequency of preterm birth and low birthweight. However, no beneficial effect of this treatment on perinatal mortality or severe neonatal respiratory disorders could be detected. PMID- 2897208 TI - Platelet vinculin: a substrate of activated factor XIII. AB - In addition to plasma, Factor XIII of blood coagulation (FXIII) is also present in the cytosol of platelets, monocytes and macrophages. However, its intracellular function has not yet been revealed. Activated Factor XIII (FXIIIa) is a transglutaminase (protein-glutamine: amine gamma-glutamyltransferase, EC 2.3.2.13) of highly restricted substrate specificity with only a few known protein substrates. In this report, we showed that FXIIIa can link dansylcadaverine, radiolabelled histamine and putrescine to vinculin. Quantitative determinations revealed that in the vinculin molecule a single glutamine residue can serve as acyl donor for the incorporation of small molecular-weight amines. Vinculin could not be crosslinked to another vinculin molecule. It could be covalently bound, however, to fibrinogen, which indicates that the acyl donor glutamine residue can be engaged in an epsilon-(gamma glutamyl)lysyl crosslink formation. Since it has been shown that platelet actin and myosin, two main components of cytoskeleton, are also substrates for FXIIIa, and that vinculin is associated to the cytoskeleton during platelet activation, the involvement of FXIII in the stabilization of cytoskeleton at certain phases of cellular function is a likely possibility. PMID- 2897209 TI - Activation of guanylate cyclase and inhibition of platelet aggregation by endothelium-derived relaxing factor released from cultured cells. AB - The aggregation of gel-filtered rabbit platelets by 50 microM ADP was inhibited by a labile factor produced by suspensions of cultured bovine pulmonary artery endothelial cells. Inhibition of aggregation occurred when indomethacin-treated endothelial cells (6.10(5) per ml) and rabbit platelets (3.2.10(8) per ml) were incubated together. This anti-aggregatory activity was characterized as similar to endothelium-derived relaxing factor (EDRF) in that it was unstable at neutral pH and by its inhibition by hemoglobin. The activity was unaffected by treatment of the platelets and endothelial cells with the cyclooxygenase inhibitor, indomethacin, and by the lipoxygenase inhibitor, BW755c. In association with the anti-aggregatory activity, the levels of cyclic GMP were elevated 4-fold. The effect of the EDRF-like product on the levels of cyclic nucleotides was mimicked by treatment of platelets with sodium nitroprusside, an activator of soluble guanylate cyclase; sodium nitroprusside had no measurable effect on the levels of cyclic nucleotides of endothelial cells. We conclude that a factor with the properties of EDRF inhibits platelet aggregation, and that this is associated with an activation of guanylate cyclase as in smooth muscle. Thus, EDRF may exert an inhibitory effect on platelets in a manner analogous to its actions on vascular smooth muscle. PMID- 2897210 TI - The biopotency of dexamethasone at causing hepatic glucocorticoid receptor down regulation in the intact mouse. AB - The effect of dexamethasone administered intraperitoneally on hepatic glucocorticoid receptor binding capacity was measured in adrenalectomized male Swiss Webster mice. The liver content of dexamethasone was also measured. Within 30 min of a 5 micrograms injection, the hepatic content of dexamethasone reached a maximum and fell quickly thereafter. By 6 h the hepatic content of dexamethasone had decreased to 25% of maximum and by 24 h the liver did not contain detectable dexamethasone. At this 24 h point, the glucocorticoid binding capacity was reduced to 50% of control. This decrease reflected down-regulation. Other studies revealed that only glucocorticoids caused this effect and doses of dexamethasone as low as 0.5-5 ng caused a clear down-regulation in binding capacity. Doses that cause receptor down-regulation are also effective at inducing tyrosine aminotransferase, suggesting that dexamethasone down-regulates its own receptors over a physiologically meaningful dosage range. It is concluded that dexamethasone causes a dose-dependent down-regulation of the glucocorticoid receptor in mouse liver. PMID- 2897211 TI - Ligation of fibrinogen by factor XIIIa with dithiothreitol: mechanical properties of ligated fibrinogen gels. PMID- 2897213 TI - Interaction of metronidazole with phenobarbital, cimetidine, prednisone, and sulfasalazine in Crohn's disease. AB - The influence of prednisone(PR), sulfasalazine(SZ), cimetidine(CM), and phenobarbital(PB) on the pharmacokinetics of metronidazole was investigated in six Crohn's patients. Metronidazole was first administered alone (250 mg bid, po) and then with prednisone (10 mg bid, po), sulfasalazine (1 g bid, po), cimetidine (600 mg bid) or phenobarbital (60 mg bid, po). Each regimen was followed for 6 days and sampling of blood and urine was carried out on the 7th day after the first dose of each regimen. Plasma and urine samples were analysed for the drug and its two principal metabolites, hydroxymetronidazole and metronidazole-1 acetic acid, by HPLC. When given alone, metronidazole had a mean volume of distribution of 0.667 +/- 0.15 lkg-1, a half-life of 9.7 +/- 3.1 h and an oral clearance of 0.852 +/- 0.23 (ml-1 min) kg-1. The disposition kinetics of metronidazole and its metabolites was not altered by CM and SZ. Induction of metabolism of metronidazole by PR was made manifest in significant increases in oral clearance of the former and urinary excretion of the hydroxy metabolite, and significant decrease in AUC of the parent compound. PB also induced the metabolism of metronidazole. This induction was reflected in significant increases in the oral clearance of metronidazole and AUC of the hydroxy metabolite as well as significant decreases in AUC, half-life, and urinary excretion of the parent drug. PMID- 2897212 TI - Pharmacokinetics of indoramin and its 6-hydroxylated metabolite after repeated oral dosing. AB - The pharmacokinetics of indoramin and its active 6-hydroxylated metabolite have been studied in healthy male volunteers after repeated oral dosing with 37.5 mg twice daily for 2 weeks. Plasma concentrations of indoramin accumulated, on average, three to four-fold above those anticipated on the basis of the kinetics after the first dose, though steady state was achieved by the end of the first week and no further increase was observed after 2 weeks. The degree of accumulation was consistent between subjects, with a highly significant (p less than 0.001) correlation between the concentration 2 h after a single dose and the average steady-state concentration. Possible explanations for the accumulation of indoramin are discussed. Plasma concentrations of 6-hydroxyindoramin, in contrast, did not accumulate on multiple dosing. At steady state, concentrations of the metabolite, as represented by the AUC0-8h, were approximately 30-40 per cent of those of the unchanged drug. Since the two compounds are approximately equipotent the metabolite may accounts for 25 per cent of the hypotensive activity of indoramin during a typical clinical regime of 37.5 mg twice daily. PMID- 2897214 TI - Morphological changes in rat tracheal mucosa immediately after antigen challenge. AB - We have investigated the morphological effects of an intratracheal challenge with 50 micrograms ovalbumin (OA) on sensitized rat tracheas, in vivo. Female Sprague Dawley rats were primed ten days before challenge with a single i.t. injection of 100 micrograms OA plus Bordetella pertussis (OA-BP). Two additional groups of animals served as controls: primed animals challenged with saline only and non primed but OA-challenged animals. Sacrifices--and subsequent morphological studies--were performed prior to and 5, 15 and 60 min after challenge. At each time, the total numbers of epithelial nuclei, subepithelial mast cells (SEMC) and intraepithelial mast cells (IEMC) were scored in six non-adjacent cross sections per trachea. We found that: 1) priming with OA-BP alone did not induce any change in the tracheal mucosa with respect to morphological structure and mast cell counts; 2) no morphological change nor significant modification of the cell counts occurred at any time in tracheas from either of the control groups; 3) in contrast, a luminal heterogeneous exudate and a subepithelial oedema developed in 9 of the 15 tracheas of primed animals within 60 min of OA challenge. In those nine tracheas, the scores of intraepithelial nuclei, of IEMC and of SEMC were found to decrease significantly 15 min after challenge as compared with starting values (p less than 0.05 for each score). The decrease in the number of mucosal mast cells is probably related to the damages of the epithelial cells and to the difficulty with which depleted mast cells can be seen by toluidine blue staining. PMID- 2897215 TI - Sulphasalazine and PhCL28A inhibit the formation of ethanol- and phenylbutazone induced rat gastric ulcers: lack of involvement of endogenous prostaglandins? AB - 1. The effects of sulphasalazine (SZP) and PhCL28A on macroscopic lesion formation and ex vivo prostaglandin inactivation were studied in the ethanol (ETOH) and phenylbutazone (PBT) models of gastric ulcers in the rat. Prostaglandin 'synthesis' during homogenisation of the stomachs was also studied in the latter model. 2. Both PhCL28A and SZP when injected i.p. prevented the formation of ETOH- and PBT-induced gastric ulcers with ED50 values of 13 and 41 mgkg-1 (vs ETOH) and 3 and 32 mgkg-1 (vs PBT) for PhCL28A and SZP respectively. However, neither compound was active orally in the dose ranges used (up to 30 mg kg-1 for PhCL28A and 100 mg kg-1 for SZP). 3. Irrespective of the route of administration, SZP (100 mg kg-1) and PhCL28A (30 mg kg-1) produced slight but statistically significant decreases in ex vivo prostaglandin inactivation by 100,000 g cytosolic supernatants prepared from stomachs not receiving ulcerogen. When tested in vitro, PhCL28A (IC50 = 230 nM) was approximatively 480 times mor potent than SZP (IC50 = 110 microM) against rat stomach cytosolic prostaglandin inactivation. 4. Both ETOH (50%, 5 ml kg-1, orally) and PBT (200 mg kg-1, orally) significantly decreased ex vivo gastric cytosolic prostaglandin inactivation. PhCL28A (30 mg kg-1, orally or i.p.) decreased prostaglandin inactivation still further after ulcerogen treatment except when given i.p. before ETOH treatment. SZP (100 mg kg-1) had a similar effect when given orally before PBT treatment. 5. When the prostaglandin content of the stomach homogenates was used as a measure of ex vivo prostaglandin synthesis in the PBT experiments, PhCL28A 30 mg kg-' orally (but not i.p.) produced an 88% increase in prostaglandin E2 (PGE2) levels, but had no effect on 6-keto-PGF,, or thromboxane B2 formation during homogenization. SZP (100mg kg' i.p. or orally) was without effect. 6. We conclude from these results that the anti gastric ulcer activity of SZP and PhCL28A is independent of prostaglandin inactivation and endogenous prostaglandin formation is probably not involved. PMID- 2897216 TI - Functional and direct binding studies using subtype selective muscarinic receptor antagonists. AB - 1. Muscarinic receptor antagonists were examined in direct binding studies on guinea-pig cardiac and cortical muscarinic receptors. Pirenzepine, dicyclomine and hexahydroadiphenine were shown to be selective ligands for the putative M1 muscarinic receptor. 2. Functional affinity estimates of the muscarinic ligands studied was determined from their ability to inhibit carbachol-stimulated inositol phosphate (IP) accumulation in guinea-pig cortical slices. 3. The affinity estimates for the inhibition of muscarinic agonist-stimulated IP accumulation were better correlated with affinity estimates obtained from binding studies on the M1 than the M2 muscarinic receptor. 4. These data provide additional evidence, both from direct binding and functional studies, for the presence of M1 and M2 muscarinic receptor subtypes. PMID- 2897217 TI - Celiprolol: a positive inotropic beta-adrenoceptor blocking agent in conscious dogs. AB - 1. beta-Adrenoceptor blocking agents are used to manage various cardiovascular disorders. A limiting factor in their use is the suppression of the cardiac contractile state. In our study, we examined the cardiac effects of celiprolol, a new beta-adrenoceptor blocking agent with reported positive inotropic effects. 2. Dogs were instrumented by use of sterile surgical techniques for the study of myocardial inotropic state, heart rate and internal left ventricular dimensions. Following complete recovery from surgery, experiments were conducted in the conscious state. 3. Intravenous injection of celiprolol (3 mg kg-1) in nine dogs, increased LV dP/dt by 13 +/- 2.6%, velocity of shortening (LV dD/dt) by 9.2 +/- 3.4%, and heart rate by 19 +/- 4.6% and decreased LV end-diastolic diameter by 1.8 +/- 0.8%, all significantly (P less than 0.05). Celiprolol blocked the inotropic actions of isoprenaline (0.5 micrograms kg-1) but only partially reduced its hypotensive effects. Propranolol, in contrast, reduced LV dP/dt by 17 +/- 3.3% and heart rate by 8.1 +/- 2.7% (P less than 0.05) while totally abolishing the hypotension, tachycardia and increase in LV dP/dt caused by isoprenaline. Following beta-adrenoceptor blockade with propranolol and with heart rate held constant by electrical pacing, celiprolol increased LV dP/dt by 16 +/- 4.0%, LV dD/dt by 12 +/- 3.0% and reduced LV end-diastolic diameter by 3.5 +/- 0.5% (P less than 0.05). 4. Thus, in conscious dogs, celiprolol increases inotropic state and reduces preload independently of beta 1-adrenoceptor mechanisms and the Bowditch phenomenon, while effectively blocking beta 1 receptors in the heart. These properties would make celiprolol useful in patients where a conventional beta-adrenoceptor blocking agent might lead to pump failure. PMID- 2897218 TI - Mechanisms of action of lipoxygenase and cytochrome P-450-mono-oxygenase inhibitors in blocking endothelium-dependent vasodilatation. AB - 1. Acetylcholine, ionophore A23187 and melittin induced endothelium-dependent relaxations of preconstricted strips of rabbit aorta. These relaxations are likely to be mediated by endothelium-derived relaxing factor (EDRF). 2. Relaxations in response to acetylcholine (1 microM) were inhibited by the following lipoxygenase inhibitors, with the approximate IC50 values indicated in parentheses: gossypol (1.5 microM), nordihydroguairetic acid (NDGA, 5 microM), AA 861 (20 microM), phenidone (30 microM), quercetin (40 microM), BW 755C (300 microM), and piriprost (500 microM); with cirsiliol 50% inhibition was not achieved. Acetylcholine-induced relaxations were also blocked by the cytochrome P 450-mono-oxygenase inhibitors proadifen (SKF 525A, 4 microM), metyrapone (300 microM), and cimetidine (300 microM); 7,8 benzoflavone had no effect up to 100 microM. 3. The more potent inhibitors were also tested against relaxations induced by A23187 (0.1 microM) and melittin (1 microM) and produced partial inhibition of these relaxations. 4. The mechanism of action of the more potent inhibitors was investigated in a bioassay system. EDRF was produced in columns filled with cultured human endothelial cells. The factor was bioassayed with endothelium denuded segments of rabbit femoral artery. When added to effluent of the column, NDGA, AA861, proadifen and metyrapone inhibited the EDRF-induced vasodilatation, whereas gossypol had no effect. Gossypol, however, blocked EDRF production when infused through the column. 5. The more potent inhibitors were also tested to determine their effect on purified soluble guanylate cyclase. While gossypol, NDGA and proadifen had no appreciable effects, basal and nitroprusside (50 microM)-stimulated guanylate cyclase activity was inhibited by AA861 and metyrapone. 6. These data suggest that many of the above compounds inhibit EDRF by mechanisms other than lipoxygenase- or cytochrome P-450-mono oxygenase inhibition. PMID- 2897219 TI - Evidence that inhibitory factor extracted from bovine retractor penis is nitrite, whose acid-activated derivative is stabilized nitric oxide. AB - 1. Unactivated extracts of bovine retractor penis (BRP) contains 3-7 microM nitrite. Acid-activation of these extracts at pH 2 for 10 min followed by neutralization generates the active form of inhibitory factor (IF; assayed by its vasodilator action on rabbit aorta), and is associated with partial loss of nitrite. 2. Increasing the time of acid-activation at pH 2 from 10 to 60 min with intermittent vortex mixing generates greater vasodilator activity and increases nitrite loss. 3. When acid-activated and neutralized extracts are incubated at 37 degrees C or 30 min or boiled for 5 min, vasodilator activity is lost and nitrite content increased. Reactivation of these samples at pH 2 for 10 min followed by neutralization leads to partial recoveries of vasodilator activity with loss in nitrite content. 4. Addition of sodium nitrite to BRP extracts increases acid activatable vasodilator activity pro rata. 5. Acid-activation of aqueous sodium nitrite solutions results in less loss of nitrite and generation of less vasodilator activity than BRP extracts. Vasodilatation is only transient and is rapidly abolished on neutralization, whereas responses to acid-activated BRP extracts are more prolonged and activity is stable on ice. 6. Bovine aortic endothelial cells yield vasodilator activity that is indistinguishable from that isolated from BRP. It is activated by acid, stable on ice, abolished by boiling or by haemoglobin, and appears to be due to the generation of nitric oxide (NO) from nitrite. 7. The data provide confirmatory evidence that nitrite in BRP extracts is IF, that acid-activation of BRP extracts yields NO which is responsible for its vasodilator action, and that inactivation occurs by decay of NO to nitrite and nitrate. They further suggest that BRP extracts contain a NO stabilizing agent which favours conversion of nitrite to NO. 8. The finding that bovine aortic endothelial cells yield an agent indistinguishable from IF suggests that nitrite in endothelial cells may likewise be the precursor of endothelium derived relaxing factor (EDRF), itself identified as NO. PMID- 2897222 TI - Destruction of cells in the midportion of the locus coeruleus by a dorsal bundle lesion in neonatal rats. AB - Although insult of the developing noradrenergic neuronal system in the brain has been associated with redistribution of noradrenergic fiber input to various target brain regions, few studies have investigated the effects of such insults on locus coeruleus cell survival. In the present study the dorsal noradrenergic bundle was transected by means of a midbrain knife cut in rats 3 days after birth, and the effects of this lesion were determined approximately 8-10 weeks later. By means of an immunofluorescent histochemical procedure, it was shown that tyrosine hydroxylase-containing fibers and dopamine beta-hydroxylase containing fibers were markedly reduced in number in the neocortex and hippocampus--regions anterograde to the site of axonal transection. It was further demonstrated that the number of fluorescent fibers coursing through the dorsal bundle was similarly reduced. Sprouting of noradrenergic fibers in the brainstem and cerebellum accompanied the above alterations. When locus coeruleus cell number was determined by counting Cresyl violet-stained nucleoli in serial sections it was found that dorsal bundle transection produced a loss of 17% of the cells of the coeruleus. By dividing the counts for each nucleus into fifths, it was additionally found that approximately 20-25% of those cells comprising the midportion of the nucleus, along a rostrocaudal axis, were the ones destroyed by axonal transection. These findings indicate that a neonatal lesion of the dorsal bundle produces a loss of cells in the midportion of the nucleus locus coeruleus, and that this effect is associated with noradrenergic neuronal hyperinnervation of the brainstem and cerebellum. PMID- 2897220 TI - A quantitative pharmacological analysis of some excitatory amino acid receptors in the mouse neocortex in vitro. AB - 1. The effects of 2-amino-5-phosphonovalerate and kynurenate, either alone or in combination, were tested on responses evoked by the excitatory amino acid agonists quinolinate, ibotenate, N-methyl-D-aspartate and N-methyl-DL-aspartate by use of an in vitro preparation of mouse neocortex and artificial cerebrospinal fluid nominally free of magnesium. 2. Schild plots for 2-amino-5 phosphonovalerate, using each of the excitatory amino acids, were linear and had a slope not significantly different from one. The apparent pA2 values for 2-amino 5-phosphonovalerate using each of the excitatory amino acids were 4.98 (quinolinate), 5.00 (N-methyl-DL-aspartate), 4.92 (N-methyl-D-aspartate) and 5.05 (ibotenate). The apparent pA2 obtained using ibotenate was distinct from that of N-methyl-D-aspartate but there were no significant differences between pA2 estimates for quinolinate, N-methyl-D-aspartate or N-methyl-DL-aspartate. 3. Schild plots for kynurenate, using each of the excitatory amino acids, were linear and had a slope of 1.36 +/- 0.03, significantly greater than one. The estimated apparent pA2 values for kynurenate were 3.65 (quinolinate), 3.71 (N methyl-DL-aspartate), 3.65 (N-methyl-D-aspartate) and 3.89 (ibotenate). The apparent pA2 obtained using ibotenate was distinct from that of the other agonists. 4. Experiments using combinations of 2-amino-5-phosphonovalerate and kynurenate indicated that both antagonists apparently acted competitively at receptors activated by ibotenate or by quinolinate. 5. These results indicate that ibotenate acts at a site distinct form that of quinolinate, N-methyl-D aspartate and N-methyl-DL-aspartate. PMID- 2897221 TI - Electrical and mechanical properties of the capsular smooth muscles of the rabbit prostate in relation to the actions of the alpha 1-adrenoceptor blocker, YM 12617. AB - 1. Electrical and mechanical properties of smooth muscle cells of the rabbit prostate capsule and the actions of the alpha 1-adrenoceptor blocker, YM-12617, were investigated using microelectrode and isometric tension recording methods. 2. The capsular muscles comprised thick and thin muscle bundles. In the former, noradrenaline (NA; 0.1-10 microM) provoked the phasic and tonic mechanical responses, with twitch contractions superimposed on the tonic response. YM-12617, in concentrations over 1 nM inhibited the contraction evoked by any given concentration of NA. Yohimbine (up to 10 microM) slightly inhibited the NA induced contraction whilst clonidine (up to 10 microM) and acetylcholine (ACh; up to 10 microM) produced no mechanical response. 3. In thin muscle bundles, NA (0.1 10 microM) produced a contraction but the phasic response was small and the tonic response was negligible. These changes were blocked by YM-12617. In contrast, ACh (0.1-10 microM) produced atropine-sensitive, large phasic and tonic responses similar to those observed on application of NA to thick muscle bundles. 4. In thin and thick muscle bundles, the mean resting membrane potentials were -54 and 56 mV, respectively, values which were not statistically different. However, in thick muscle bundles, NA (over 0.1 microM) depolarized the membrane in a concentration-dependent manner and produced repetitive spike generation; ACh (up to 1 microM) did not modify the membrane potential. In thin muscle bundles, the above concentrations of NA hyperpolarized the membrane but ACh produced a large depolarization with repetitive spike generation. 5. In thick muscle bundles, nifedipine (0.3 microM) blocked twitch contractions generated spontaneously or provoked by application of NA with no effect on phasic and tonic responses. The NA-induced depolarization persisted after superfusion with nifedipine up to a concentration of 1.0 microM. In a Ca-free solution containing 2 mM EGTA, NA produced only the phasic responses, and re-addition of Ca (2.6 mM) restored the generation of a tonic response. 6. After application of 0.3 microM nifedipine, the effects of YM-12617 and prazosin were observed on the tonic component of the NA-induced contraction of thick muscle bundles. The ID50 values for YM-12617 and prazosin were 1 nM and 15 nM, respectively (n = 4). YM-12617 shifted the NA concentration-response curve to the right in a concentration-dependent and parallel manner. The Schild plot yielded a straight line with slope of 0.97 +/- 0.05, (n = 4). The pA2 value for YM-12617 was 10.4 +/- 0.05, (n = 4). 7. In thiqk muscle bundles, the depolarization induced by NA (1O microM) was blocked by YM 12617 (over 1 nM) to a greater extent than by prazosin (0.1 microM). Half inhibition of the NA (10 microM)-induced maximum depolarization by YM-12617 or prazosin occurred at concentrations of 2 nm and 100 nM, respectively. 8. From these mechanical and electrical responses, the heterogeneous nature and distribution of alpha-adrenoceptors and muscarinic receptors has been elucidated in capsular smooth muscles in the rabbit prostate. In both thick and thin muscle bundles, NA-induced electrical and mechanical responses were more potently inhibited by YM-12617 than by prazosin. PMID- 2897223 TI - Isolation of less than Glu-Ser-Leu-Arg-Trp-NH2, a novel neuropeptide from sea anemones. AB - Using a radioimmunoassay for the peptide sequence Arg-Phe-NH2, a peptide has been purified from acetic acid extracts of the sea anemone Anthopleura elegantissima. This peptide has the structure less than Glu-Ser-Leu-Arg-Trp-NH2. Using antisera to its carboxyterminal sequence Arg-Trp-NH2, the peptide was found to be exclusively localized in neurons of sea anemones, among them neurons associated with the sphincter muscle. This suggest that the peptide is a transmitter at neuromuscular junctions. PMID- 2897224 TI - Influence of stereotaxically injected scrapie on neurotransmitter systems of mouse cerebellum. AB - The 22L strain of scrapie was injected stereotaxically into the cerebellum of C57BL/6J mice to determine its effect on several cerebellar neurotransmitter systems during the early clinical stages of the disease. In this model vacuolar lesions are restricted to the cerebellum with no evidence of vacuolization in other brain regions. Although vacuolar lesions develop throughout all cell layers of the cerebellum, they are most severe in the granule cell layer. Modest but significant (P less than 0.01) reductions in cerebellar weight, glutamate decarboxylase activity, and in the affinity of the N6-[adenine-2,8 3H]cyclohexyladenosine binding sites, were observed in scrapie affected mice. The densities of the high- and low-affinity adenosine receptors were unaffected. Adenosine receptors in the cerebellum are highly localized to the axon terminals of the glutamatergic, GABA receptive granule cells. GABA, benzodiazepine, glutamate, and muscarinic cholinergic receptors were not significantly altered. In addition, the high-affinity uptake of glutamate, and the activity of choline acetyltransferase were not significantly changed. GABA high-affinity uptake was slightly increased. Even though the granule cell layer of the cerebellum had undergone severe vacuolation, only modest neurotransmitter changes were apparent. Although these results suggest a tenuous relationship between scrapie pathology and the integrity of neurotransmitter systems, it is possible that compensatory neurochemical changes in uncompromised neuronal populations may have masked potentially specific neurotransmitter effects. PMID- 2897225 TI - Adrenal medullary cells transmute into dopaminergic neurons in dopamine-depleted rat caudate and ameliorate motor disturbances. AB - Adrenal medullary cell suspensions, derived from newborn rats (postnatal day 1 6), were implanted into the head of the caudate nucleus in 35 rats with unilateral 6-hydroxydopamine (6-OHDA) lesions in the nigrostriatal dopamine (DA) pathway. Behavioral recovery from Met-amphetamine induced circling, cell growth and morphological features (tyrosine hydroxylase positive cells), and release of adrenaline (Ad), noradrenaline (NA), DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were investigated for 40 weeks after transplantation. Met-amphetamine induced circling decreased significantly in 43% (15/35) of the rats. The decrease was concurrent with transmutation of the tyrosine hydroxylase like immunopositive (THLI) cells into mature neurons that had abundant elongated neurites with varicosities and synapses on neuronal elements in the host caudate. In the absence of behavioral recovery (57%, 20/35) THLI cells were very scant. DA, DOPAC and HVA were reduced more than 90% in perfusates collected by in vivo dialysis from the striata of the animals that were not improved by transplant. These levels recovered to 20-50% of controls in animals whose behavior recovered. Ad and NA were not detected in the perfusates of either recovered or non recovered animals. The results suggest that some grafted adrenal medullary cells transform into dopaminergic neurons and the release of DA from these grafted cells functionally affects behavior improvement for at least 40 weeks. PMID- 2897226 TI - Differential sensitivity of neuropeptide Y, somatostatin and NADPH-diaphorase containing neurons in rat cortex and striatum to quinolinic acid. AB - The tryptophan metabolite quinolinic acid (QUIN) was injected unilaterally into rat cerebral cortex or striatum in order to determine whether the neurotoxin would destroy neuropeptide Y (NPY)- and somatostatin (SS)-immunoreactive, and NADPH-diaphorase (NADPH-D)-containing neurons. Following intrastriatal injections of QUIN, NPY and SS immunoreactivity and NADPH-D-activity was absent in the injection core area. In contrast, cortical NPY- and SS-immunoreactive cells and NADPH-D-containing neurons were resistant to QUIN's neurotoxicity. These results suggest that in contrast to striatal neurons, cortical SS- and NPY-containing neurons do not express N-methyl-D-aspartate receptors. PMID- 2897227 TI - Cortical lesions increase reinnervation of the dorsal striatum by substantia nigra grafts. AB - Effects of aspiration lesions of the cerebral cortex on intraventricular substantia nigra grafts were investigated. Increased reinnervation of the dorsal striatum was observed in animals with cortical aspirations. This reinnervation was confined to the dorsal one-fourth of the striatum, immediately underneath the cortical lesions. The increased reinnervation of the striatum by substantia nigra grafts in animals with cortical lesions is suggested to be related either to secretion of neurotrophic substances by the injured brain tissue or to removal of competition between corticostriatal inputs and graft-derived neurites for synaptic contacts. PMID- 2897228 TI - Toxic effects of MDMA on central serotonergic neurons in the primate: importance of route and frequency of drug administration. AB - This study compared the toxic effects of oral versus subcutaneous and single versus multiple doses of 3,4-methylenedioxymethamphetamine (MDMA) on central serotonergic neurons in non-human primates. Orally administered MDMA was approximately one-half as effective as subcutaneously administered drug. Multiple doses were more effective than single doses, but a single 5 mg/kg dose of MDMA given orally still produced a long-lasting depletion of serotonin in the monkey brain. These results indicate that when MDMA is given to monkeys in a manner similar to that employed by humans, it exerts toxic effects on central serotonergic neurons. This suggests that humans using MDMA may be at risk for incurring central serotonergic neuronal damage. PMID- 2897229 TI - Electrophysiological actions of norepinephrine in rat lateral hypothalamus. I. Norepinephrine-induced modulation of LH neuronal responsiveness to afferent synaptic inputs and putative neurotransmitters. AB - The present studies were conducted as part of an ongoing investigation of the effects of norepinephrine (NE) in neuronal circuits of the mammalian brain. In this report, we describe noradrenergic actions in the lateral hypothalamus (LH), an area which has been implicated in the central integration of cardiovascular regulatory mechanisms, fluid balance and ingestive behaviors. Microiontophoretically applied NE was interacted with extracellularly recorded responses of LH neurons to iontophoretically applied putative neurotransmitters gamma-aminobutyric acid (GABA), acetylcholine (ACh) and glutamate (Glu); and activation of known input pathways from the reticular thalamus (RT) and the lateral preoptic area (LPO). Peri-event histograms of cell responses were computed before, during and after NE microiontophoresis (5-50 nA) and used to quantitatively evaluate monoamine-induced effects on spontaneous and stimulus evoked activity of LH neurons. In 16 of 23 LH neurons, RT-stimulus-induced inhibition was markedly prolonged from a mean of 28.3 +/- 4.8 ms to 44.7 +/- 5.2 ms, during iontophoretic application of NE. In 22 of 38 LH cells, LPO-stimulus induced excitatory responses were enhanced above control levels during NE administration. In further tests, inhibitory responses of LH cells to iontophoretic pulses of GABA were potentiated during NE administration in 69% (24 of 35) of the cases tested. ACh-induced excitation was potentiated in 9 of 21 cells. In 4 of these cases, otherwise subthreshold doses of ACh caused marked increases in cell firing during the period of NE administration. By contrast, Glu evoked excitation was antagonized by NE iontophoresis in 65.5% (17 of 26) of LH cells tested. These findings indicate that, as in other noradrenergic target regions of the CNS, NE can facilitate synaptically mediated responses of LH neurons. Taken together these observations suggest that NE may play an important regulatory role in the synaptic transfer of information within LH circuits, and consequently exert considerable influence over the homeostatic functions mediated by this structure. PMID- 2897230 TI - gamma-L-glutamyl-L-aspartate induces specific deficits in long-term memory and inhibits [3H]glutamate binding on hippocampal membranes. AB - gamma-L-Glutamyl-L-aspartic acid (gamma-LGLA) has been isolated from Datura stramonium; its structure has been determined and it was then synthesized. In male Swiss mice intraperitoneal administration of the natural peptide (125 nmol/kg) or of the synthetic peptide (25-2500 nmol/kg) 24 h after acquisition of a Y-maze avoidance task induced a dose-dependent deficit in retention performance 48 h later. gamma-LGLA had no effect on locomotor activity or emotional reactivity at the doses used. Separate or simultaneous administration of aspartate or glutamate (each at 250 nmol/kg) had no effect on learning retention, indicating that deficit induced by gamma-LGLA was specific to the peptide. gamma LGLA impaired learning acquisition in a time-dependent manner when administered from 3 min to 24 h post-training, but had no effect when administered 3 days following acquisition. gamma-LGLA administered just after the training session did not affect retention performance during the first 3 h, but suppressed the retention improvement observed in control animals from 6 to 24 h after acquisition; this deficit was still evident 7 days after the treatment. gamma LGLA partially inhibited L-[3H]glutamate binding on crude hippocampal or striatal membrane preparations; this inhibition was not observed on cerebellar membrane preparations. These results suggest a specific action of gamma-LGLA on excitatory amino acid systems which may be responsible for its effects on learning retention. PMID- 2897231 TI - Pterygopalatine ganglion cells contain neuropeptide Y. AB - By immunohistochemistry, neuropeptide Y (NPY) localizes to neurons in the rat pterygopalatine ganglion. These cells also are intensely or moderately reactive with acetylcholinesterase histochemistry. In contrast, both tyrosine hydroxylase immunohistochemistry and glyoxylic acid-induced fluorescence for catecholamines stain smaller clustered cells, similar in appearance to small intensely fluorescent (SIF) cells and clearly distinct from the NPY-immunoreactive cells. By reverse phase high-performance liquid chromatography, the NPY-immunoreactive material in the rat pterygopalatine ganglion migrates as a single peak characteristic of the peptide. We conclude that NPY-containing cholinergic cells are present in this classical parasympathetic ganglion. NPY-like immunoreactive neurons similarly occur in the pterygopalatine ganglion of the guinea pig. PMID- 2897233 TI - beta-Phenylethylamine enhances single cortical neurone responses to noradrenaline in the rat. AB - The firing rates of single neurones in the rat cerebral cortex were recorded using multibarrel glass microelectrodes, and the response to drugs applied by microiontophoresis was investigated. A greater number of cells responded to noradrenaline (NA) (30-66 nA) than to beta-phenylethylamine (PE) (30-100 nA). When responses were obtained to both, 90% of the neurones gave the same response to NA and PE. Applications of PE with small currents (0-12 nA) caused an increase in the response to NA without affecting the baseline firing rate or the response to acetylcholine, glutamate, GABA or 5-hydroxytryptamine. An increase was seen in both excitatory and inhibitory responses to NA. The enhancement lasted up to 39 minutes after the end of the PE application. Applications of NA with small currents (0-3 nA) failed to alter responses to NA. Possible mechanisms of the effect of PE on response to NA are discussed. These results provide further evidence for the hypothesis that trace amines can modulate catecholamine neurotransmission. PMID- 2897232 TI - Saline ingestion stimulates the in situ molar activity of tyrosine hydroxylase in the median eminence and superior cervical ganglion. AB - The effects of drinking saline for 7 days on the mass and in situ activity of tyrosine hydroxylase (TH) in the median eminence (ME) and superior cervical ganglion (SCG) of rats were investigated. TH mass was quantified by immunoblot assay. In situ TH activity was calculated from the rate of intracellular accumulation of L-dihydroxyphenylalanine (DOPA). In rats that drank 10 mM, 30 mM, and 100 mM NaCl for 7 days, TH activity in the ME was 34 +/- 4, 36 +/- 5, and 45 +/- 3 (mean and S.E.M.) mol of DOPA.h-1.mol of TH-1, respectively, compared to 30 +/- 2 for rats that drank water. The activity of TH in the SCG of animals that drank 10 mM, 30 mM, and 100 mM NaCl was 143 +/- 24, 167 +/- 12, and 272 +/- 13 mol DOPA.h-1.mol TH-1, respectively, compared to 119 +/- 10 for animals that drank water. The mass of TH in the ME and SCG decreased as a function of the concentration of NaCl in the drinking water. In animals that drank water, 10 mM, 30 mM, and 100 mM NaCl, the amounts (pmol) of TH were, respectively, 0.28 +/- 0.03, 0.31 +/- 0.04, 0.23 +/- 0.02, and 0.21 +/- 0.01 per ME and 0.67 +/- 0.06, 0.72 +/- 0.11, 0.37 +/- 0.01, and 0.34 +/- 0.02 per SCG. TH activity in the ME or SCG was unaffected by treatment for 7 days with arginine vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897234 TI - Rat atrial natriuretic peptide (99-126) stimulates guanylate cyclase activity in rat subfornical organ and choroid plexus. AB - The effect of rat atrial natriuretic peptide (99-126) (rANP) on cyclic guanosine 3',5'-monophosphate production was investigated in two brain areas, the subfornical organ and the choroid plexus. rANP activated guanylate cyclase in crude homogenates of rat subfornical organ and choroid plexus in concentration and time dependent fashions. A 2-fold stimulation of the enzyme was obtained with 100 nM rANP and a half-maximal stimulation with a 10 nM dose. Our results further support the hypothesis that cGMP mediates the central action of ANP through the activation of specific receptors in localized target sites such as the subfornical organ and choroid plexus. PMID- 2897235 TI - Degradation and conversion of somatostatin in normal and diabetic rats in vivo and in vitro. AB - Plasma somatostatin-like immunoreactivity in the portal and jugular veins of streptozotocin diabetic rats was compared with that in normal control rats. In the diabetic group, somatostatin levels in the portal (p less than 0.05) and jugular (p less than 0.01) veins were both elevated compared with those in the control group. Moreover, the degree of elevation was greater in the jugular vein than in the portal vein. To further investigate the role of the liver in the clearance of somatostatin-28 in vivo, 2 micrograms of somatostatin-28 was administered as a bolus into the external jugular vein of intact and functionally hepatectomized rats. The mean half-time of somatostatin-28 was significantly longer in intact diabetic rats than in controls (p less than 0.05). The functional hepatectomy did not cause a significant difference in the half-time in diabetic rats but made it longer in control rats. These results suggest that the longer half-time of somatostatin-28 in diabetic rats in vivo is due to its slower hepatic clearance. The hepatic clearance of somatostatin-28 and somatostatin-14 was further studied in vitro using a recirculating liver perfusion method. The hepatic clearance of 1.2 nM of either somatostatin-28 or somatostatin-14 was significantly lower in diabetic rats than in controls (p less than 0.01). This indicates that elevated plasma somatostatin levels in diabetic rats are caused at least in part by decreased hepatic clearance of somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897236 TI - Increased pulmonary vascular capacitance with beta-adrenergic receptor stimulation: an experimental study of the effect of isoproterenol on the pulmonary vascular volume-pressure relationship. AB - The present study is an investigation of the effect of beta-adrenergic receptor stimulation by isoproterenol on pulmonary vascular capacitance. The experiments were done in six intact-chest, anaesthetized dogs in which pulmonary and cardiac blood volumes were assessed by blood pool scintigraphy. Isoproterenol (0.150 microgram.kg-1.min-1) significantly (p less than 0.005) lowered pulmonary capillary wedge pressure (PPCW) and pulmonary artery pressure (PPA) but did not significantly change pulmonary blood volume (PBV). Left ventricular end-diastolic pressure and total cardiac volume both significantly (p less than 0.005) decreased. Pulmonary vascular volume-pressure (V-P) relationships before and during isoproterenol were described by means of blood transfusions and hemorrhage. In individual dogs the PBV-PPCW and the PBV-(PPCW + PPA)/2 relationships were significantly shifted upward by isoproterenol (p less than 0.05 or less); slope changes were variable. Pooled data from all dogs also showed a significant (p less than 0.001) upward shift in the pulmonary vascular V-P relationship regardless of which measure of distending pressure was used. These results suggest that beta-receptor stimulation by isoproterenol increases pulmonary vascular capacitance by increasing the unstressed volume. PMID- 2897237 TI - Coated pits and vesicles in the osteoclast. AB - The osteoclast is a cell with a phagocytic ability not dissimilar to the macrophage. Nevertheless, the mechanisms by which it resorbs bone are poorly understood. The aim of this study was to examine the distribution of coated membrane structures in the osteoclast in order to gain further information about endocytosis in this cell. Osteoclasts around the developing tooth germs of young rats were examined using transmission electron microscopy, and immunocytochemistry. Results showed that previously described coated membrane structures within the ruffled border do not appear to be associated with coated pits or vesicles. Coated pits were, however, evident on the dorsal and lateral surfaces of the cell, particularly opposite the clear zone areas. Immunogold staining for clathrin confirmed that coated pits and vesicles are absent within both the clear zone and ruffled border areas, but present on the lateral and dorsal surfaces of the actively resorbing cell. It is suggested that clathrin associated receptor-mediated endocytosis occurs along the lateral and dorsal surfaces of the osteoclast for the uptake of nutrients and macromolecules, while endocytosis of bone mineral by the ruffled border is mediated by a non-clathrin associated coated membrane structure. PMID- 2897238 TI - cis-diamminedichloroplatinum(II)-resistant sublines derived from two human ovarian tumor cell lines. AB - In two human ovarian tumor cell lines, resistance to cis diamminedichloroplatinum(II) (CDDP) was induced by continuous exposure of the parental lines to an increasing CDDP concentration in the culture medium. In contrast, a six times repeated pulse exposure of 6.7 microM or 16.7 microM CDDP for 1 h did not result in a cell line that showed a higher survival in CDDP containing medium. The ID50 value for CDDP was seven to eight times higher for the resistant lines and those lines were able to grow at 3.3 microM CDDP. The induced resistance was stable during at least 25 doubling times. The CDDP resistant sublines showed cross-resistance to the CDDP-analogues cis-diammine-1,1 cyclobutane-dicarboxylateplatinum(II) and cis-dichlorobis(isopropylamine)-trans dihydroxyplatinum(IV) indicating that resistance to the different platinum compounds is generated by a common mechanism. The resistant sublines were also cross-resistant to mitomycin C and melphalan. The degree of cross-resistance for the tested drugs varied widely between the two cell lines. Resistance to CDDP was clearly correlated to decreased amounts of platinum in the resistant cells as compared to the sensitive cells. The amplification and expression of genes encoding proteins that had been shown to be involved in multidrug resistance, e.g., the Mr 170,000 P-glycoprotein was also studied. No amplification or overexpression of these genes could be shown in the resistant cell lines. PMID- 2897239 TI - Effects of a new alpha 1-blocker, bunazosin hydrochloride, on plasma lipid components in hypertensive patients with hypercholesterolemia. AB - Oral bunazosin hydrochloride, a new alpha 1-blocker, for 12 weeks was given to ten outpatients diagnosed as having essential hypertension associated with hypercholesterolemia. High-density lipoprotein (HDL) triglyceride, HDL3 cholesterol, and apolipoprotein E levels were significantly decreased by bunazosin treatment. The decrease in HDL triglycerides was a result of the decrease in HDL3 triglyceride levels. There were no significant changes in the other components. The ratio of cholesterol to triglycerides in the low-density lipoprotein (LDL) and HDL fractions was increased significantly after bunazosin treatment. Furthermore, the ratio of HDL2 cholesterol to HDL3 cholesterol after bunazosin treatment was significantly higher than before treatment. The results suggest that the catabolism of triglycerides in lipoprotein and the reduction in tissue cholesterol increase, and that bunazosin hydrochloride does not adversely affect the lipid component in hypertensive patients with hypercholesterolemia. PMID- 2897240 TI - An altered pattern of cross-resistance in multidrug-resistant human cells results from spontaneous mutations in the mdr1 (P-glycoprotein) gene. AB - Multidrug resistance in human cells results from increased expression of the mdr1 (P-glycoprotein) gene. Although the same gene is activated in cells selected with different drugs, multidrug-resistant cell lines can be preferentially resistant to their selecting agent. The mdr1 cDNA sequence from vinblastine-selected KB cells, which are uniformly resistant to different lipophilic drugs, was compared with the corresponding sequence from colchicine-selected KB cells preferentially resistant to colchicine. These sequences differ at three positions, resulting in a single amino acid change in P-glycoprotein. These differences result from mutations that occurred during colchicine selection. The appearance of these mutations coincides with the emergence of preferential resistance to colchicine. We have constructed biologically active mdr1 cDNA clones that express either wild type or mutant P-glycoprotein. Multi-drug-resistant transfectants obtained with the mutant sequence were characterized by increased relative resistance to colchicine compared with transfectants obtained with wild-type sequence. mdr1 mutations are therefore responsible for preferential resistance to colchicine in multidrug-resistant KB cells. PMID- 2897241 TI - Differential regulation of Ultrabithorax in two germ layers of Drosophila. AB - The homeotic gene Ultrabithorax (Ubx) is expressed in specific parts of Drosophila embryos: in a single metamer in the visceral mesoderm and forming a complex pattern limited to a broad domain in the ectoderm and in the somatic mesoderm. Here we use a linked beta-galactosidase gene to identify cis-acting regulatory sequences. In the visceral mesoderm, correct expression of Ubx depends on localized upstream sequences. In the ectoderm, all galactosidase-positive transformants show the same characteristic pattern. The repeated elements of this basal pattern appear to be a sub-pattern of engrailed (en) expression; they depend on en function as well as on sequences in the Ubx RNA leader. We use a mutant (Haltere-mimic) to show that sequences that normally restrict segmental expression of Ubx in the ectoderm are located downstream from the RNA leader. PMID- 2897242 TI - Microinjection of synthetic Xhox-1A homeobox mRNA disrupts somite formation in developing Xenopus embryos. AB - The structural similarity between Drosophila and vertebrate homeobox genes begs the question of whether the vertebrate gene products affect cell fate and pattern formation. To study the function of the Xenopus homeobox protein, Xhox-1A, we microinjected fertilized Xenopus eggs with an excess of synthetic Xhox-RNA and assayed for effects on development. The predominant phenotype is a disturbance in somite formation. When embryos are injected with Xhox-1A mRNA, but not with control mRNAs, morphogenesis of somites occurs chaotically and individual segments are lost. Histological staining, in situ hybridization, and immunohistochemistry indicate that the disorganized somitic tissue has differentiated into muscle cells. Overall, these results suggest that correct regulation of the Xhox-1A gene may be important for the normal development of the segmented somite pattern in early embryos. Moreover, the inferred role of Xhox-1A in somite formation indicates that there may be molecular parallels between mechanisms of segmentation in flies and vertebrates. PMID- 2897243 TI - Transcription factors that activate the Ultrabithorax promoter in developmentally staged extracts. AB - We have initiated a biochemical analysis of factors that regulate the expression of the Ultrabithorax (Ubx) homeotic gene during embryogenesis. Transcriptionally active extracts have been prepared from Drosophila embryos at successive stages of development that recreate in vitro the temporal profile of Ubx gene expression during embryogenesis. Multiple sequence-specific transcription factors have been detected that bind to essential cis control elements located upstream and downstream of the Ubx mRNA cap site. The activity of some of these transcription factors varies during embryogenesis, and some are detected in embryonic extracts but not in Drosophila tissue culture cells. One factor, which binds to multiple GAGA DNA sequence motifs in the Ubx promoter, has been purified and shown to activate transcription from this promoter in a binding site-dependent manner. This in vitro analysis should help in understanding how Ubx expression is regulated and provide insight into the processes determining cellular fates during development. PMID- 2897244 TI - A single amino acid change in the cytoplasmic domain allows the influenza virus hemagglutinin to be endocytosed through coated pits. AB - Through site-specific mutagenesis, three of the ten amino acids of the cytoplasmic domain of the influenza virus hemagglutinin (HA) were individually changed to tyrosines. None of these changes had significant effect on the rate of export, the rate of folding, or the antigenicity of the mutant HAs. However, one of these mutations, substituting tyrosine for cysteine at amino acid 543, changed HA from a protein that was endocytosed at a very low rate to a protein that readily entered coated pits, was internalized, and apparently recycled to the cell surface. Replacement of cysteine 543 with phenylalanine or serine did not increase the rate of internalization of HA. Phosphorylation of the mutant HA bearing a tyrosine at position 543 was not detected. These results indicate a specific and local role for the tyrosine introduced into the cytoplasmic domain of HA that is necessary for interaction of the protein with coated pits. PMID- 2897245 TI - The jellyfish and its polyp: a comparative study of gene expression monitored by the protein patterns, using two-dimensional gels with double-label autoradiography. AB - The life cycle of Podocoryne carnea (Coelenterata, Anthomedusae) shows several distinct stages which differ considerably in terms of their ecology, morphology, cellular composition, and ultrastructure. Previously these stages had even been described as separate species. Using two-dimensional gel electrophoresis and a new method of double-label autoradiography, we show here for the first time for metagenic hydrozoans that only minor differences in gene expression exist between the various life cycle stages. Our results demonstrate the high resolution power of these techniques and show that the different life stages of P. carnea remain rather similar on the protein level. Most of the prominent spots of the two dimensional gel protein patterns are common to all stages studied. These data show that the hydrozoan life cycle and development are regulated by only minor distinctions in gene expression which possibly explains the great morphogenetic repertoire of these animals described in many studies. PMID- 2897246 TI - Oxidative mitogenesis: participation of CD2 antigen in the generation and/or transduction of obligatory accessory signals. AB - We investigated the role of cluster designation 2 (CD2) antigen in the activation of human T cells using either soluble phase or crosslinked monoclonal anti-CD2 antibodies, and oxidizing mitogens as probes. Soluble phase anti-CD2 inhibited oxidative mitogenesis when accessory signals were delivered with accessory cells and not when 12-O-tetradecanoylphorbol-13-acetate or interleukin 2 provided the required accessory signals. Soluble phase anti-CD2 also inhibited accessory cell dependent increases in intracellular free calcium concentration and cell-to-cell contact among oxidizing mitogen-treated T cells and accessory cells. Crosslinked anti-CD2, on the other hand, generated the required accessory signals and functioned as an accessory cell substitute. Also, signals initiated by crosslinked anti-CD2 were able to replace accessory cell signals only, and not the mitogenic signals initiated with the oxidizing mitogens. Collectively, these findings indicate that the CD2 antigen participates in the generation and/or transduction of accessory signals obligatory for oxidative mitogenesis. PMID- 2897247 TI - Transforming growth factor-beta s are equipotent growth inhibitors of interleukin 1-induced thymocyte proliferation. AB - The effects of two forms of transforming growth factor-beta, TGF-beta 1 and TGF beta 2, upon the proliferative response of murine thymocytes were investigated in this study. TGF-beta 1 and TGF-beta 2 were found to be equipotent growth inhibitors of interleukin-1 (IL-1)- and phytohemagglutinin (PHA)-stimulated thymocytes when added at the initiation of the cultures. These factors suppressed the proliferative response in a dose-dependent fashion between 0.4 and 100 pM. The proliferative response was maximally inhibited (90% inhibition) at 100 pM. The half-maximal inhibitory dose (ID50) was 6 and 4 pM for TGF-beta 1 and TGF beta 2, respectively. These factors were less effective or ineffective at suppressing the proliferation of thymocytes which had been prestimulated for 24 to 48 hr by IL-1 and PHA. Neither factor inhibited interleukin-2 (IL-2)-dependent thymocyte proliferation or the proliferation of an IL-2-dependent cytotoxic T cell line (CTL-L), suggesting that the anti-proliferative actions of these factors was by inhibition of cellular events triggered by IL-1. Furthermore, anti TGF-beta 1 antibodies did neutralize the biological actions of TGF-beta 1 and these antibodies did block the binding of 125I-labeled TGF-beta 1 to cell surface receptors showing that the inhibitory action is mediated through specific receptors for TGF-beta 1 on thymocytes. These antibodies, however, did not neutralize the anti-proliferative action of TGF-beta 2. Although TGF-beta 1 and TGF-beta 2 exhibit very similar biological activities, these molecules are antigenically different and, therefore, have different tertiary structures. PMID- 2897248 TI - Nucleotide sequencing analysis of a LEU gene of Candida maltosa which complements leuB mutation of Escherichia coli and leu2 mutation of Saccharomyces cerevisiae. AB - The expression of a LEU gene from Candida maltosa (designated as C-LEU2) isolated previously (Kawamura et al. 1983) was shown to be regulated, when transferred into Saccharomyces cerevisiae, by leucine and threonine in the medium, as in the case of LEU2 gene of S. cerevisiae. The coding region together with the regulatory region was subcloned and the nucleotide sequence was determined. When the sequence of the coding region was compared with that of LEU2, the homology was 72% for base pairs and 76% for deduced amino acids. Comparison of the regulatory region of C-LEU2 with those of LEU1 and LEU2 suggested a few short consensus sequences which are involved in regulation of gene expression by leucine and threonine in the medium. PMID- 2897249 TI - Arginine repression of the Saccharomyces cerevisiae ARG1 gene. Comparison of the ARG1 and ARG3 control regions. AB - The Saccharomyces cerevisiae ARG1 gene coding for argininosuccinate synthetase has been isolated and the nucleotide sequence of both its control region and of its amino terminal end coding region determined. The startpoint of transcription was established by S1-mapping and reverse transcriptase procedures. Northern blot hybridizations showed that whereas arginine-specific repression reduced the enzyme activity fivefold, it did not reduce the steady state level of the corresponding messenger in proportion; by analogy with the coregulated ARG3 gene, this result suggests a post-transcriptional regulatory mechanism. In contrast, proportionally between enzyme activity and mRNA content was observed under conditions where general amino acid control (known to be transcriptional) was operating. Comparing the 5' untranscribed domains of ARG1 and ARG3 revealed a first region of homology between the TATA box and the transcription startpoint. In this region a 10 bp (ARG3) or 11 bp (ARG1) central box is flanked by two segments which, by mutation, have been shown to be part of the ARG operator (Crabeel et al. 1985). The repressor is assumed to bind at this primary target site prior to establishing contacts with the proximal part of the nascent mRNA molecule (Crabeel et al. 1985). By in vitro directed deletion mutagenesis we show that the central conserved box of ARG3 is not essential for arginine-specific repression to occur. Another region of homology was found in the leader part of the messenger RNA; deletion of this region causes a small reduction in ARG3 expression but also does not alter regulation. Neither of these two regions are thus part of the primary repressor target site. In addition, in terms of post transcriptional regulation, the latter result indicates that no sequence specificity is required in the RNA recognition step. PMID- 2897251 TI - Plastome mutation affecting the chloroplast ATP synthase involves a post transcriptional defect. AB - In a plastid genome (plastome) mutation of Oenothera hookeri, at least two of the plastome-coded polypeptides (the beta and epsilon subunits) of the chloroplast ATP synthase are directly affected. As in other plastid chromosomes, the genes for the beta and epsilon subunits are located next to each other on the Oenothera ptDNA molecule and are cotranscribed. Immunoanalysis and peptide mapping of in vivo products suggests that a fusion of the two genes may have occurred in the plastome mutant. In contrast to the in vivo data, in vitro translation of the RNA using a heterologous system results in polypeptides which cannot be distinguished from those of wild-type. In addition, neither the mRNA sizes nor plastid DNA restriction fragment patterns differ from wild-type. To reconcile the paradox of these results, it is suggested that either a defect in a translational signal or some other post-transcriptional event is responsible for the mutant phenotype. PMID- 2897252 TI - The circadian rhythms of thyrotrophin and prolactin secretion. AB - As with other anterior pituitary hormones, the secretion of both thyrotrophin (TSH) and prolactin (PRL) displays a circadian variation with different patterns for each hormone. In recent years there has been a substantial increase in the understanding of the neuroregulation of TSH and PRL. However the primary events involved in the generation of their circadian rhythms remains unclear. Regulatory pathways comprise two major groups: central factors, where the control is exerted by the central nervous system via the hypothalamus and peripheral factors, which include all extra CNS mechanisms. The first group is represented mainly by neuropeptides and neurotransmitters controlling TSH and PRL release, whereas the second one comprises both physical phenomena such as variations in plasma volume or postural changes and hormonal influences arising from target glands such as the adrenal, the thyroid and the gonads. PMID- 2897250 TI - A fine restriction map of the linear mitochondrial DNA of Tetrahymena pyriformis: genome size, map locations of rRNA and tRNA genes, terminal inversion repeat, and restriction site polymorphism. AB - A fine restriction map of the linear mitochondrial DNA of Tetrahymena pyriformis strain ST is presented. 1. Based on agarose gel electrophoresis data together with limited nucleotide sequences available on some restriction fragments, we estimate the actual size of this genome to be about 55,000 base pairs. 2. Seven tRNA gene locations have been assigned, which are scattered along the genome length. Six of these locations encode the genes for tRNA(phe), tRNA(his), tRNA(trp), and tRNA(glu), and the duplicate tRNA(tyr) genes which are located at the inverted terminal repeat segments. The tRNA gene(s) encoded in one location has not been identified. We have not yet found the tRNA(leu) and tRNA(met) genes, which were previously shown to be encoded in the genome (Chiu et al. 1974; Suyama 1982). 3. We have mapped the 14S rRNA gene by sequencing the 170 bp segment of EcoRI fragment 8 and by aligning its sequence with E. coli 16S rRNA. From our recent complete sequence data the gene size was found to be about 1,650 bp, which is unexpectedly large for the 14S rRNA which has an estimated size of 1,300 bp. The 14S rRNA is probably a cleavage product of the larger primary transcript of which 200-300 bases of the 5' end are missing. 4. The duplicate copies of the 21S rRNA gene at the terminal duplication inversion segments were analyzed. ClaI fragment 7 (1,500 bp) corresponds in sequence from base position 850 to 2,390 of the 20S rRNA gene of Paramecium mitochondrial DNA (Seilhamer et al. 1984b). The 21S gene is approximately 2,500 bp long. The presence of some restriction site polymorphism is apparent in this segment. 5. Each of the 21S gene copies precedes the tRNA(tyr) gene, but the space flanking one tRNA(tyr) gene differs in size and restriction sites from the space flanking another tRNA(tyr) gene. Thus, this space corresponds to the segment of an imperfect match in the terminal duplication inversion of Goldbach et al. (1978a). 6. Saccharomyces cerevisiae mitochondrial probes including Cob, ATPase VI and IX, and cytochrome oxidase I gene sequences, 21S and 15S rRNAs, and mouse mitochondrial DNA showed no significant hybridization with any restriction fragments of Tetrahymena mitochondrial DNA. The results are in accordance with an extensive sequence divergence previously found in the Tetrahymena mitochondrial genome (Goldbach et al. 1977). PMID- 2897253 TI - [Non-conventional central nervous system agents]. PMID- 2897254 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin and polycyclic aromatic hydrocarbons suppress retinoid-induced tissue transglutaminase in SCC-4 cultured human squamous carcinoma cells. AB - Retinoic acid and retinyl acetate induce tissue transglutaminase to high levels in cultured SCC-4 keratinocytes, increasing the enzyme specific activity over 50 fold under optimal conditions. Pretreatment of the cells for a day with 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3-MC) or benzo[a]pyrene almost completely prevented the induction observed upon subsequent treatment with retinoic acid for 2 days. Similar aromatic compounds that do not induce aryl hydrocarbon hydroxylase (pyrene, dibenzofuran) did not exhibit this suppressive effect. The concentration dependence on TCDD for induction of aryl hydrocarbon hydroxylase was nearly identical to that for its suppression of transglutaminase induction, with half-maximal effects observed at approximately 20 pM in each instance. Similarly, the concentrations of 3-MC giving half-maximal stimulation of the hydroxylase and suppression of the transglutaminase were comparable (0.9 and 0.3 microM, respectively), although this agent was almost five orders of magnitude less potent than TCDD. These observations reveal a loss of cellular sensitivity to vitamin A mediated by the Ah receptor. PMID- 2897255 TI - Reversal by ribo- and deoxyribonucleosides of dehydroepiandrosterone-induced inhibition of enzyme altered foci in the liver of rats subjected to the initiation--selection process of experimental carcinogenesis. AB - The effect of dehydroepiandrosterone (DHEA) on the activity of NADPH-producing enzymes and the development of enzyme-altered foci has been investigated in the liver of female Wistar rats subjected to an initiating treatment (a necrogenic dose of diethylnitrosamine) followed, 15 days later, by a selection treatment [a 15-day feeding of a diet containing 0.03% 2-acetylaminofluorene (2-AAF), with a partial hepatectomy at the midpoint of this feeding]. At the end of the selection treatment all rat groups received, for 15 days, a basal diet containing, when indicated, 0.05% phenobarbital (PB) and/or 0.6% DHEA. The effect of DHEA on the activity of NADPH-producing enzymes was also studied in normal rats fed, for 15 days, a diet containing 0.6% DHEA and in their pair-fed controls. DHEA caused a 43-58% inhibition of glucose-6-phosphate dehydrogenase (G6PD) and, respectively, 338-420% and 21-24% increases in malic enzyme (ME) and isocitric dehydrogenase activities in all rat groups. This was coupled with a great fall in the production of ribulose-5-phosphate, while no change in NADP+/NADPH ratio occurred. Hepatocytes, isolated from DHEA-treated rats, exhibited a very low activity of hexose monophosphate shunt (HMS), which was not stimulated by methylene blue, an exogenous oxidizing agent that markedly stimulated HMS activity in control hepatocytes. DHEA caused a great fall in the percentage of liver occupied by gamma-glutamyltranspeptidase (GGT)-positive foci, in the rats subjected to the initiation-selection treatments. PB enhanced the development of these foci, an effect which was completely overcome by DHEA. In addition, focal cells no longer expressed a G6PD activity higher than that of surrounding liver in DHEA-treated rats, but exhibited a high histochemical reaction for ME. DHEA also caused a great fall in labelling index of GGT-positive foci. Starting at the end of 2-AAF feeding, a mixture of ribonucleosides (RNs) of adenine, cytosine, guanine and uracil and of deoxyribonucleosides (DRNs) of adenine, cytosine, guanine and thymine were injected i.p. every 8 h for 12 days to the rats subjected to the initiation-selection treatments plus PB. Rats were killed 3 days after the end of RN and DRN treatments. These treatments completely overcome the DHEA effect on the development of GGT-positive foci and DNA synthesis by the focal cells, without affecting G6PD activity of both whole liver and putative preneoplastic foci. Experiments with labeled nucleosides revealed that RNs and DRNs produced derivatives that were incorporated into liver DNA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2897256 TI - Colorimetric assay of blood coagulation factor XIII in plasma. AB - In this new colorimetric assay for Factor XIII in plasma, 5 (biotinamido)pentylamine is used as the amine substrate. Factor XIII, a zymogen, is transformed by thrombin and Ca2+ to active Factor XIIIa, and the incorporation of 5-(biotinamido)pentylamine into N,N-dimethylcasein is used to measure catalytically active Factor XIIIa. The biotinylated enzymatic product is immobilized onto 96-well microtiter plates, complexed with streptavidin-beta galactosidase, and the absorbance at 405 nm is monitored for production of p nitrophenol from p-nitrophenyl-beta-D-galactopyranoside. Concentrations of N,N dimethylcasein, 5-(biotinamido)pentylamine, Ca2+, and thrombin were chosen to allow near-maximum velocity of amine incorporation. A linear relationship was obtained between assay product and plasma volume, from 0.5 to 50 microL of plasma. Results correlated well (r greater than 0.924) with those from the most frequently utilized radiometric filter-paper assay for Factor XIII. The method appears to be ideal for routine diagnostic estimation of Factor XIII in plasma because of its simplicity, its lack of use of radioisotopes, and its potential for assay of large numbers of samples by use of microtiter plates and automated plate readers. PMID- 2897257 TI - Prenatal diagnosis of cystic fibrosis: microvillar enzymes and DNA analysis compared. AB - We have established reference ranges for three microvillar intestinal enzymes- alkaline phosphatase (EC 3.1.3.1), gamma-glutamyltransferase (EC 2.3.2.1), and leucine aminopeptidase (EC 3.4.1.1)--measured in amniotic fluid in a reference population of 1875 women presenting for routine amniocentesis. These data were derived for use in prenatal diagnostic studies in a population at risk (1:4) for cystic fibrosis. False-positive or indeterminate results were noted for fewer than 3.5% of all low-risk cases for each enzyme evaluated. Total alkaline phosphatase and its isoenzymes and leucine amino-peptidase and gamma glutamyltransferase were measured in amniotic fluid sampled between the 15th and 19th weeks of gestation. Restriction fragment length polymorphism analysis of DNA was also performed when possible. In 52 cases examined for cystic fibrosis thus far, 46 were diagnosed on the basis of DNA analysis and (or) by sweat testing; for the other six cases, only abnormal enzyme results were obtained before termination of pregnancy. Predictions based on microvillar enzyme results were falsely negative in three cases. In only one case was there a discrepancy between enzyme results and DNA analysis. Diagnostic accuracy was highest during the 17th and 18th week of gestation. Preliminary results suggest the false-negative rate of this diagnostic strategy may be greater than or equal to 10%. PMID- 2897258 TI - Urinary alanine aminopeptidase assay improved as result of multivariate response surface analysis. AB - Optimization of determination of alanine aminopeptidase in urine by univariate study led to a method involving pretreatment of urine with Sephadex G50. Re examination of the optimization by multivariate study led us to recommend higher optimal concentrations: 5.8 mmol/L for the substrate and 300 mmol/L for the Tris buffer. Under these new conditions, pretreatment of urine was no longer necessary and the assay could be completely automated. PMID- 2897259 TI - MDMA and MDA cross reactivity observed with Abbott TDx amphetamine/methamphetamine reagents. PMID- 2897260 TI - Growth hormone and prolactin secretion after growth hormone-releasing hormone administration, in anorexia nervosa patients, normal controls and tamoxifen pretreated volunteers. AB - Anorexia nervosa is associated with several abnormalities in GH secretion elicited by different stimuli. To investigate the precise mechanism of this alteration, GHRH was administered to 14 women: a group of eight anorexia nervosa patients in the acute phase of their illness and a control group of six age matched volunteers. As patients with anorexia nervosa have chronic low oestrogen values, the volunteer women of the control group underwent a second GHRH test after pretreatment with the oestrogen receptor blocker tamoxifen. GHRH 1-29 (1 microgram/kg i.v.) induced a GH peak (mean +/- SEM) of 28.2 +/- 5.1 ng/ml (GH ng/ml x 2 = mU/l) at 30 min in the anorectic patients. This value was no different from the GHRH-stimulated GH peak in the control women (28.1 +/- 10.0 ng/ml). Tamoxifen pretreated women had a GH peak after GHRH of 35.6 +/- 9.7 ng/ml, not significant versus control test. Compared with the control group, oestrogen levels were significantly lower in anorectic patients and higher in tamoxifen-treated women. GHRH administration induced a small PRL peak at 15 min that was similar in the three groups tested. After this 15 min peak, PRL in both anorexic and tamoxifen-treated women returned toward basal values steadily. However, in untreated control women a second PRL peak was evident at 60 min. In conclusion, GHRH-induced GH secretion in anorexia nervosa patients was similar to that in control subjects and in controls under oestrogen receptor blockade. PMID- 2897261 TI - Multiple symmetric lipomatosis (Launois-Bensaude syndrome): effect of oral salbutamol. AB - A 65-year-old Kenyan Asian developed rapidly progressive multiple symmetrical lipomatosis over 8 years. Noradrenaline infusion showed a normal response of plasma free fatty acids. In-vitro studies of the lipomatous tissue demonstrated intact lipolytic activities with a normal rate of free fatty acids release and cyclic AMP accumulation with or without isoprenaline and fenoterol stimulation. A clinical trial of oral salbutamol, a beta 2-agonist, was performed with significant therapeutic effect. The body fat mass showed a reversal of the rapid progression while on the treatment, associated with an increase in the resting metabolic rate. PMID- 2897262 TI - Sipple's syndrome associated with a large prolactinoma. AB - A 26-year-old male presented with the symptoms and signs of acute congestive heart failure and hypertension. The left ventricle was shown to be thickened and displayed reversible hypokinesia. Further investigations revealed the underlying pathology of a phaeochromocytoma, bilateral medullary thyroid carcinoma (MTC), parathyroid adenoma and macro-prolactinoma. There was a family history of MTC. The echocardiographic features of catecholamine-induced cardiomyopathy were important in this diagnosis. Our research revealed no previous report of Sipple's syndrome associated with a macroprolactinoma. This case, along with the other 13 reports of mixed (type I and II) multiple endocrine neoplasia (MEN), are not within the classical subsets of MEN. PMID- 2897263 TI - In-vitro conversion of blocking type anti-TSH receptor antibody to the stimulating type by anti-human IgG antibodies. AB - We examined the relationship between blocking type anti-TSH receptor antibody (TRAb) and stimulating type TRAb by trying to convert blocking type TRAb to the stimulatory type in vitro. Immunoglobulins (IgGs) purified from sera of six patients with primary hypothyroidism blocked bovine TSH (100 microU/ml)-induced cAMP production (58.3-82.1% inhibition) in cultured porcine thyroid cells. None of these IgGs showed stimulating activity even after their dilution. In the conversion experiment, thyroid cells were first incubated with these IgGs at 34 degrees C for 30 min and then washed with incubation buffer. They were then incubated with various kinds of anti-human IgG antibodies first for 1.5 h at 4 degrees C and then for 18 h at 34 degrees C, and the cAMP concentrations in the supernatants were measured. All six IgGs showed strong, dose-dependent thyroid stimulating activity after addition of antibodies against human whole IgG, or Fab or Fc fragments of IgG. The Fab or F(ab')2 fragments of goat anti-human IgG antibody also had these converting activities, although less than whole IgG. Addition of normal IgG in the first incubation or anti-human IgG antibody alone had no thyroid-stimulating activity. Anti-human IgA or IgM antibodies did not have these converting activities. These results show that blocking type anti-TSH receptor antibodies can be converted to the stimulating type by anti-human IgG antibodies in vitro. The results suggest that the blocking and stimulating types bind to the same epitope(s) of TSH-receptor related antigens. The same anti-TSH receptor antibody may act as a stimulator or blocker by the influence of other factors, such as anti-idiotype antibody. PMID- 2897265 TI - Prevention and treatment of preterm labor in twins. AB - It is well established that mothers with twin gestations are at a significant risk of giving birth to a premature infant and, compared to singletons, the perinatal mortality and morbidity are significantly increased. Unfortunately, it is clear that little progress has been made over the past two decades in either the prevention or the treatment of premature labor in twins. The clinician is left with more questions than answers. This latter aspect needs to be recognized by the legal profession. Obviously, more studies regarding the possible beneficial effect of either bedrest or prophylactic beta-sympathomimetics are needed before meaningful recommendations can be made on a universal basis. It is also obvious that more potent tocolytic agents are needed to actually treat premature labor once it occurs. Taking all of these facts into consideration, the authors would recommend the protocol outlined in Table 3 for the general management of twins with regard to premature labor. PMID- 2897264 TI - Iodine-131 MIBG uptake in metastatic medullary carcinoma of the thyroid. A patient treated with somatostatin. AB - A 47-year-old man with multiple endocrine neoplasia (MEN) type 2a syndrome in whom metaiodobenzylguanidine (MIBG) concentrated in lesions from metastatic medullary carcinoma of the thyroid is reported. A somatostatin analogue (Sandostatin SMS 201-995) alleviated the symptoms of flushing and diarrhea associated with the elevated calcitonin levels but it did not alter either the course of the disease or the MIBG images. A review of the literature is presented of the noncatecholamine secreting tumors associated with MIBG uptake. Similarities between this case and metastatic carcinoid syndrome are discussed. PMID- 2897266 TI - Partial enterectomy decreases somatostatin-binding sites in residual intestine of rabbits. AB - 1. Three weeks after partial enterectomy in the rabbit there was an increased somatostatin concentration and a decreased number of somatostatin-binding sites (without changes in the corresponding affinity values) in the cytosol of the residual intestinal tissue, except in the terminal ileum and the colon. 2. Five weeks after surgery both the somatostatin concentration and the number of somatostatin-binding sites returned towards control values. 3. These results suggest that an increase in bowel somatostatin content could lead to down regulation of somatostatin-binding sites in the intestinal mucosa. PMID- 2897267 TI - A rise in the plasma activities of hepatic enzymes is not a common consequence of hypoglycaemia. AB - Eight otherwise healthy insulin-dependent diabetic patients were subjected to controlled, symptomatic hypoglycaemia for 20 min (median glucose concentration 1.7 mmol/l, range 1.0-2.6 mmol/l). Concentrations of plasma adrenaline and plasma vasopressin were significantly increased, indicating normal counter-regulatory responses for these hormones. Plasma activities of the hepatic enzymes AST, ALT, LDH, GGT, and CK did not increase during or following the period of hypoglycaemia. Thus, abnormal plasma enzyme activities noted after clinical hypoglycaemia should be fully investigated, and not disregarded as due to the hypoglycaemic episode. PMID- 2897268 TI - Acute pain management: the role of patient-controlled analgesia. PMID- 2897269 TI - Novel 'soft' beta-blockers as potential safe antiglaucoma agents. AB - A series of novel "soft" beta-blockers was designed and synthesized based on the "inactive metabolite approach". Accordingly, the acidic metabolite of metoprolol was converted into various lipophilic esters. The new compounds were tested for their effect on the intraocular pressure (IOP) of rabbits using the ultra-short acting beta-adrenergic antagonist "Esmolol" as a reference compound. Most of the tested compounds displayed a higher and a more prolonged ocular hypotensive activity than the reference methyl ester. The adamantaneethyl ester 2 emerged as the best potential candidate for ophthalmic use as an antiglaucoma agent. This compound exhibited an effective and long lasting ocular hypotensive activity without local irritation to the eye. At the same time, it showed a very fast rate of hydrolysis in human blood (t1/2 = 7.0 minutes) to the inactive acid metabolite. This makes possible effective separation of the desired ocular activity from unwanted systemic beta-blocking action. Unilateral treatment with 2 produced reduction in the IOP only in the treated eye, consistent with the mechanism proposed. PMID- 2897270 TI - Diptera mosquitoes. PMID- 2897271 TI - Neurohumoral regulation of airway contractile responses. PMID- 2897273 TI - Histamine H2 receptor antagonists and blood alcohol levels. PMID- 2897272 TI - Impaired exocrine pancreatic function in diabetics with diarrhea and peripheral neuropathy. AB - Exocrine pancreatic insufficiency has been observed in some diabetics with peripheral neuropathy and diarrhea. Several mechanisms may be responsible for this insufficiency: (1) pancreatic atrophy, (2) disruption of the cholinergic enteropancreatic reflexes, or (3) elevated serum levels of peptides such as glucagon and pancreatic polypeptide which are known to inhibit pancreatic exocrine secretion. To clarify the mechanism(s) involved in this exocrine pancreatic impairment, we studied 10 diabetics with diarrhea and peripheral neuropathy. Their results were compared to those of eight normal volunteers. Each subject underwent a standardized pancreatic function study which assessed nonstimulated secretion, the response to intrajejunal infusion of a mixture of amino acids, and the output following intravenous administration of secretin and cholecystokinin (CCK). In separate studies, the effect of a background infusion of bethanechol and secretin on the pancreatic response to CCK was assessed in six patients and six normal controls. Compared to normals, all diabetics exhibited a significant reduction in both enzyme and bicarbonate secretion to all stimuli. This reduction was not corrected by administering bethanechol. Plasma glucagon and pancreatic polypeptide levels in diabetics were not significantly higher than those in controls. We conclude that diabetics with diarrhea and peripheral neuropathy exhibit impairment of their exocrine pancreatic secretion and possible mechanisms for this are discussed. PMID- 2897274 TI - Insulin secretion and insulin action in Taiwanese with type 2 diabetes. AB - In contrast to the United State, type 2 diabetes appears to be a common occurrence in non-obese Asians. In order to evaluate the possibility that this epidemiologic difference was indicative of a basic metabolic phenomenon, estimates of insulin secretion and insulin action were generated in 32 Chinese males, 16 with type 2 diabetes and 16 with normal glucose tolerance. Half of the individuals in each diagnostic category were obese (body mass index greater than 28 kg/m2) and half were non-obese (less than 26 kg/m2). Plasma glucose responses to a 75-g oral glucose challenge were significantly higher in patients with type 2 diabetes, but did not vary significantly within either group as a function of obesity. Plasma insulin concentrations were lower than normal when patients with type 2 diabetes were compared to their weight-matched controls. In addition, the absolute insulin values also varied as a function of body weight, with higher plasma insulin concentrations observed in the obese individuals. Insulin action was estimated by determination of the steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations during the last 60 min of a continuous 180-min intravenous infusion of somatostatin, crystalline insulin, and glucose. Under these conditions endogenous insulin secretion is suppressed, SSPI concentrations are similar in all individuals, and SSPG concentrations provide a quantitative estimate of insulin-stimulated glucose disposal. The results of these studies indicated that patients with type 2 diabetes had significantly elevated SSPG concentrations as compared to normals, and this was true whether the diabetic subjects were obese or non-obese.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897275 TI - [DNA-binding nuclear protein factors specifically binding with the promoter elements of the tyrosine aminotransferase gene in the rat]. PMID- 2897276 TI - Haloperidol decanoate: a depot antipsychotic. AB - This article reviews the role of a new depot antipsychotic dosage form, haloperidol decanoate (HD), in relationship to other comparable pharmacotherapies (oral and injectable). The chemistry, indications, contraindications, and pharmacokinetics of HD are discussed. The available clinical research in humans is presented and evaluated with respect to efficacy, adverse effects, and dosing. HD is clearly an effective antipsychotic dosage form. Certainly, HD can improve compliance and possibly outcome for selected patients. HD should be reserved for chronic relapsing schizophrenic patients who have responded to oral haloperidol. Considering the pharmacokinetics, potential risks, and cost of HD, the clinician needs to be prepared with recommendations to effect optimal use of HD (guidelines are presented). PMID- 2897277 TI - Antipsychotics: how strict the formulary? AB - Seventeen antipsychotic medications are available in the U.S. Antipsychotic formulary considerations include relative efficacy, individual patient response, relative differences in adverse effects, dosage form availability, blood level monitoring, and generic availability. Chlorpromazine, thioridazine, haloperidol, and fluphenazine are recommended for formulary inclusion based on research and clinical considerations. A recommendation for managing a patient receiving a nonformulary antipsychotic is presented. PMID- 2897278 TI - [Asthma therapy--too much or too little?]. PMID- 2897279 TI - Glutamine synthetase: a marker of an astroglial subpopulation in primary cultures of defined brain areas. AB - Primary cultures from various areas of newborn mouse brain were developed and characterized. Enriched astroglial cultures of the cerebral hemispheres, cerebellum, medulla oblongata and olfactory bulbs contained about 80-90% glial fibrillary acidic protein (GFA) immunolabelled cells. These cultures were composed of a majority of flat, 'protoplasmic-like' cells. The aim of this culture model was used: (1) to study glutamine synthetase (GS) activity during in vitro astroglial development; (2) to consider the hydrocortisone effect on GS activity during both growth and maturation periods, and (3) to determine the development of GS immunoreactivity in the cells and eventual GFA and GS expression in these cells. We observed that GS increased during brain maturation in vivo and in vitro, and that addition of hydrocortisone (1 microM, 48 h) to the culture medium induced varying GS activity depending on the developmental stage and the area. In the four areas studied, the number and intensity of GS immunolabelled cells reached an optimum between 18 and 30 days in vitro. Only about 50-70% of the cell population was GS positive. Double-labelling experiments showed that three groups of cells coexist whatever the considered area. Two expressed both GFA and GS proteins, the last marker at either a low or a high level, and the third was devoid of GS immunoreactivity. Regional differences in GS-specific activity, GS inducibility and GS immunoreactivity exist in the astroglial population, but the factors responsible for these variations are not yet known. PMID- 2897280 TI - [Serological examination of the population of the Far East for the presence of antibodies to human T cell leukemia virus HTLV-1]. AB - Antibodies to HTLV-1 were detected in sera from 1298 healthy adult persons living in the Far East. It is shown that virus infectivity of the Nigidalts was 8%, Nivkhs--2%, Udegeits--2.9%, Oroches--2.4%, Russians--0.9%. However, the incidence of acute leukemia in these regions is low. It is suggested that these regions are not endemic areas for HTLV-1-associated haemoblastoses. PMID- 2897281 TI - [Neurotic inhibition and transnosographic approach. Apropos of a multicenter study of carpipramine]. AB - We have performed a national multicentric atrial in psychiatry, collecting 546 patients with neurotic inhibition. The efficacy of carpipramine was evaluated in this disease. A transnosographic and epidemiologic analysis of this syndrome was realized on this group of out patients. The statistical study by a factorial analysis of correspondences shows the epidemiological and symptomatic characteristics of inhibition. The endpoints were DSM-III criteria of chronic anxiety, adaptation disorders and functional sexual disorders on the first axis and different types of personality on the second axis. PMID- 2897282 TI - The inhibition of stress induced increase of liver enzyme activity by progesterone occurs in rats of both sexes. AB - Adult rats of both sexes were injected an aqueous suspension of progesterone in a dose of 12.5 mg i.p. + 12.5 mg i.m. and 50% of the animals were subjected to immobilization stress for 150 minutes either immediately after the hormone administration or at various time intervals after that. Non injected rats served as controls. After decapitation the plasma corticosterone level and the activity of tyrosine aminotransferase and tryptophan pyrrolase in the liver was determined. It was found that in non immobilized animals all three parameters investigated were increased to a minor degree 3 hours after progesterone injection. In stressed rats the stimulatory effect of stress induced hypercorticosteronaemia on the activity of both enzymes was decreased at 14 and/or 20 hours after progesterone administration, no sex differences being observed. The potential usefulness of progesterone as inhibitor of exaggerated stress is underlined. PMID- 2897283 TI - The inhibition of growth hormone release by gastrin-releasing peptide involves somatostatin release. AB - Injection of gastrin-releasing peptide-27 (GRP) into the third ventricle (IVT) has been shown previously to lower plasma GH levels and block the GH release induced by GRF, suggesting that GRP might act via stimulation of the release of somatostatin (SRIF) into hypophysial portal vessels. Several experiments were performed to test this hypothesis. In the first experiment rat median eminence (ME) fragments were incubated in medium containing concentrations of GRP ranging from 1 pM to 1 microM, and SRIF levels were measured after the 30-min incubation period. GRP significantly stimulated SRIF release at doses of 0.1 nM to 1 microM. Microinjection of SRIF antiserum (3 microliters) IVT prevented GRP (2 micrograms, IVT) from inhibiting the GH surge induced by GRF (1 microgram/kg, iv). A slight but significant decrease in basal plasma GH levels was observed after GRP administration even in the presence of SRIF antiserum. Finally, to rule out a GRP GRF interaction at the pituitary level, tubes containing dispersed rat pituitary cells (2.5 x 10(5) cells/tube) were incubated for 1.5 h in medium containing various concentrations of GRF (0.4-40 nM) alone or with 0.1 microM GRP. The addition of GRP to the medium had no significant effect on the dose-dependent stimulation of GH release by GRF. The results of these studies demonstrate that GRP can directly stimulate SRIF release in vitro. They further suggest that SRIF is a component of the mechanism whereby GRP inhibits GH release in vivo. Finally, the possibility that GRP acts at the pituitary level to inhibit GH release by blocking GRF receptors on somatotrophs has been ruled out. PMID- 2897285 TI - Paradoxical growth-promoting effects induced by patterned infusions of somatostatin in female rats. AB - In previous studies with iv infusions of GH or its releasing factor (GRF), we showed that a pulsatile pattern of GH was more effective than continuous GH exposure in stimulating growth in the rat. Since GH release is profoundly affected by its inhibitory factor, somatostatin (SS), we were interested to know whether the effects of SS on GH secretion and growth were also dependent on its pattern of administration. SS infusions were given iv to conscious chronically cannulated female rats through programmable multichannel infusion pumps. Multiple blood samples were obtained with the use of an automated system of pumps, solenoid fluid valves, and a fraction collector, all controlled by a microcomputer. SS infusions (5, 25, or 50 micrograms/h) suppressed GH secretion and elicited a rapid, short-lived rebound release of GH after stopping the infusion. Sinusoidal SS infusions in female rats produced cyclic episodes of GH secretion, but a male type of regular 3-hourly secretory pulses of GH was best achieved by prolonged infusions in which the delivery of SS was interrupted for a short period every 3 h. This intermittent SS infusion pattern elicited a repetitive series of rebound bursts of GH secretion, which increased body weight gain and pituitary GH content. In contrast, continuous infusions of equivalent amounts of SS had no effect on body weight gain and reduced bone growth significantly. Thus the effects of SS on growth do depend on the pattern in which it is administered, and this peptide, which itself powerfully inhibits GH secretion, paradoxically stimulates weight gain in a normal animal when given in a manner that promotes a more pulsatile GH secretory pattern. PMID- 2897284 TI - Somatostatin rapidly restores rat growth hormone (GH) release response attenuated by prior exposure to human GH-releasing factor in vitro. AB - To clarify the role of somatostatin (SRIF) in pulsatile GH secretion, profiles of the hormone release from intact anterior pituitaries of male rats were examined in an in vitro perifusion system. Infusion of human (h) GRF (0.1 microM) into the perifusion system for 10 min stimulated GH release, which peaked within 30-40 min. Two hours after the first stimulation, when basal GH release had not yet fallen to the original levels, the response to a second hGRF stimulation was attenuated to as low as 47.7 +/- 10.0% (+/- SE) of the first response. However, when GH release after the first stimulation had returned to the basal level after the first stimulation had returned to the basal level after perifusion with the medium for 3 h, the second response to hGRF was restored to a level similar to that of the first response. In contrast, when SRIF (0.1 microM) was infused for 50 min 1 h after the first stimulation to lower the GH baseline, the second response to hGRF was also restored to the level of the first response. Neither SRIF infusion after the first hGRF stimulation nor infusion of SRIF without hGRF caused any rebound increase in GH release after cessation of the perifusion. To determine whether SRIF exerts a direct action on the GH response, a prestimulatory perifusion with SRIF (0.1 microM) for 50 min was performed. The treatment tended to facilitate the pituitary response to hGRF. When 50-min pretreatment with SRIF at a lower concentration (0.05 microM) was given, a significantly facilitated response to the first hGRF stimulation (0.05 microM) was observed. These results suggest that 1) SRIF perifusion rapidly restores the attenuated response to a second hGRF challenge by lowering GH release to basal levels; and 2) SRIF pretreatment facilitates the GH response to the first hGRF challenge. PMID- 2897286 TI - Desensitization of rat pituitary somatotrophs to growth hormone-releasing factor occurs in vitro. AB - Desensitization of rat pituitary somatotrophs to human growth hormone-releasing factor (hGHRF) was investigated using cultured rat anterior pituitary cells. Growth hormone (GH) release decreased but the production of cAMP was still induced in response to subsequently added 10(-9) M hGHRF from cells pretreated with hGHRF at concentrations ranging from 10(-11) to 10(-7) M for 4 h. Desensitization to 10(-9) M hGHRF was also observed in cells pretreated with 10( 9) M hGHRF for 4 h in the presence of 2 mM EGTA, 10 ng/ml nifedipine or 10(-9) M somatostatin-28, which decreased GH release during pretreatment. Forskolin and A23187, at concentrations of 10(-6) M and 10(-4) M, respectively, stimulated GH release from cells pretreated with hGHRF to the same extent as that from the control cells. These results, therefore, suggest that desensitization to GHRF occurs regardless of the presence of releasable GH pool and that some changes such as uncoupling of GHRF receptors with adenylate cyclase and decreased sensitivity to cAMP of cAMP-dependent protein kinase of the secretory mechanism of GH, in addition to the decrease in releasable GH pool and down regulation of GHRF receptors, may be involved in the desensitization mechanism. PMID- 2897287 TI - Effect of uni- and bilateral cryptorchidism on testicular inhibin and testosterone secretion in rats. AB - The effect of uni- and bilateral cryptorchidism on testicular inhibin and testosterone secretion and their relationships to gonadotropins were studied in rats. Mature Wistar male rats weighing approximately 300 g were made either uni- or bilaterally cryptorchid. Testicular inhibin and testosterone content and plasma levels of LH and FSH were examined 2 weeks later. A similar remarkable decrease in testicular inhibin content was found in uni- and bilaterally cryptorchid testes. On the other hand, the testicular testosterone content was significantly decreased only in unilaterally cryptorchid testis with an inverse increase in the contralateral testis. Plasma testosterone levels were normal and plasma LH and FSH increased significantly in both of the cryptorchid groups. These results showed that cryptorchidism impairs both Sertoli and Leydig cell functions. While testosterone production was compensated by increased LH for 2 weeks, neither inhibin secretion nor storage changed in cryptorchid or contralateral testes during the same period. PMID- 2897288 TI - Free amino acids in cerebrospinal fluid from patients with infantile spasms. AB - Profiles of free amino acids in cerebrospinal fluid (CSF) were determined by high performance liquid chromatography for 20 nonneurologic control patients and 12 patients with infantile spasms. Statistical comparisons showed significantly elevated levels of lysine (p less than 0.001) and the excitatory neurotransmitter, glutamate, (p less than 0.01) for the infantile spasms group as compared to the nonneurologic control group. When the infantile spasms patients were subdivided according to the presence or absence of etiologic associations, highly elevated amino acid levels were observed only in CSF from patients of the symptomatic subgroup. The idiopathic subgroup showed levels of free amino acids that were not statistically different from those of the nonneurologic control group. These results indicate that while abnormalities of amino acid metabolism often accompany infantile spasms, no specific pattern of the major free amino acids in CSF appears to be directly related to this seizure disorder. Elevated levels of the excitatory amino acids, aspartate and glutamate, do not necessarily accompany infantile spasms, and in this study were only observed in symptomatic patients. PMID- 2897289 TI - A light-dependent dicyclohexylcarbodiimide-sensitive Ca-ATPase activity in chloroplasts which is not coupled to proton translocation. AB - The early observation of light-dependent Ca-ATPase activity in chloroplast thylakoids [Avron, M. (1962) J. Biol. Chem. 237, 2011-2017] has been reinvestigated. It is demonstrated that in contrast to light-triggered Mg-ATP activity, Ca-ATPase activity is strictly dependent on delta microH+, the transthylakoid membrane electrochemical potential gradient, since (a) there is an absolute requirement for continuous illumination; (b) electron-transport mediators that catalyze proton uptake, like phenazinemethosulphate, methylviologen of ferricyanide, are essential and (c) uncouplers inhibit the activity. The Ca-ATPase activity is essentially unaffected by dithiols, but is inhibited by CF0-CF1 inhibitors including tentoxin, dicyclohexylcarbodiimide and antisera to CF1. Addition of Ca-ATP to thylakoids does not induce delta pH or delta psi (the electrical potential gradient) formation either in the light or following preillumination with dithiols, demonstrating that it is not coupled to proton translocation. It is also demonstrated that Ca-ATP or Ca-ADP does not induce a proton leak through CF0-CF1. It is concluded that the Ca-ATPase activity in chloroplast thylakoid reflects a partial reaction of ATP synthesis catalyzed by CF0-CF1, which is internally uncoupled from proton translocation but is dependent on energization by a transmembrane delta microH+. PMID- 2897290 TI - [Influence of polymerization of D-amino acid oxidase on the behavior of the enzyme immobilized on chitosan by covalent fixation]. AB - D-Amino-acid oxidase is a flavoprotein using FAD as cofactor. The enzyme has been immobilized in the presence of FAD on a non-porous matrix: chitosan. This support is covalently bound to the enzyme with glutaraldehyde as cross-linking reagent. It is characterized by a good mechanical resistance to mechanical stirring. The enzymatic assays have been performed in batch reactor with D-phenylglycine as substrate by a spectrophotometric method which is based on the variation of the absorbance at 252 or 280 nm. The behaviour of the biocatalysts has been studied during repeated assays of 1 h at 25 degrees C in the absence of exogenous FAD. The experimental results have been compared with those obtained with the soluble enzyme tested in the presence or in the absence of FAD. The dependence of D-amino acid oxidase on FAD concentration has been studied. Immobilized enzyme on chitosan appears to be less sensitive to the association-dissociation equilibrium of FAD. This property and the capacity of the enzyme to polymerize spontaneously in solution according to the experimental conditions have been established. The fact that the enzyme can exist in various oligomeric forms is of major importance because its catalytic expression is dependent of this phenomenon. The polymerization is known to be responsible for a decrease of the maximal rate V of the enzyme. It has also been shown that in the same way this decrease was accompanied by an improvement of the affinity of enzyme for substrates. Furthermore, the value of the dissociation constant of the apoenzyme-FAD complex is significantly smaller as the degree of polymerization is high. The conclusion is that the dissociation of the cofactor can be avoided if the immobilization step is carried out at high concentration of enzyme which is favourable to its polymerization. PMID- 2897291 TI - Methanogenesis and ATP synthesis in methanogenic bacteria at low electrochemical proton potentials. An explanation for the apparent uncoupler insensitivity of ATP synthesis. AB - The rate of methane formation from H2 and CO2, the intracellular ATP content and the electrochemical proton potential (delta mu H+) were determined in cell suspensions of Methanobacterium thermoautotrophicum, which were permeabilized for K+ with valinomycin (1.2 mumol/mg protein). In the absence of extracellular K+ the cells formed methane at a rate of 4 mumol min-1 (mg protein)-1, the intracellular ATP content was 20 nmol/mg protein and the delta mu H+ was 200 mV (inside negative). When K+ was added to the suspensions the measured delta mu H+ decreased to the value calculated from the [K+]in/[K+]out ratio. Using this method of delta mu H+ adjustment, it was found that lowering delta mu H+ from 200 mV ([K+]in/[K+]out = 1000) to 100 mV ([K+]in/[K+]out = 40) had no effect on the rate of methane formation and on the intracellular ATP content. At delta mu H+ values below 100 mV ([K+]in/[K+]out less than 40) both the rate of methanogenesis and the ATP content decreased. Methanogenesis completely ceased and the ATP content was 2 nmol/mg when delta mu H+ was adjusted to values lower 50 mV ([K+]in/[K+]out less than 7). The data show that methanogenesis from H2 and CO2 and ATP synthesis in M. thermoautotrophicum are possible at relatively low electrochemical proton potentials. Similar results were obtained with Methanosarcina barkeri. Protonophoric uncouplers like 3,5,3',4' tetrachlorosalicylanilide (TCS) or 3,5-di-tert-butyl-4-hydroxy benzylidenemalononitrile (SF 6847) were found not to dissipate delta mu H+ below 100 mV in M. thermoautotrophicum even when used at high concentrations (400 nmol/mg protein). This finding explains the observed uncoupler insensitivity of methanogenesis and ATP synthesis in this organism. PMID- 2897293 TI - Beta blockers in the nineties. A European workshop. 28 March 1987, Davos, Switzerland. Proceedings. PMID- 2897292 TI - Characterization of covalently cross-linked somatostatin receptors in hamster beta cell insulinoma. AB - The selective binding of somatostatin-28 (SS-28) to beta cells of hamster insulinoma was characterized using HPLC-purified 125I-[Leu8,D-Trp22,Tyr25]SS-28 or 125I-SS-28. A single class of high-affinity sites (Kd = 53 +/- 5 pM) was observed with a binding capacity of 2.85 pmol/mg membrane protein. A large number of relatively low-affinity sites was found also. The order of potency of different peptides to inhibit 125I-SS-28 binding is SS-28 greater than SS-14 greater than SMS-201-995 and the respective half-maximal inhibitory doses are 0.16 nM, 10 nM and 1000 nM. CCK8 and other active pancreatic peptides (glucagon, insulin, gastric inhibitory peptide, vasoactive intestinal peptide, oxyntomodulin) do not inhibit the SS-28 receptor binding. 125I-SS-28-labeled beta membranes were successfully cross-linked using either the cleavable cross-linker dithiobis(succinimidylpropionate) (1 mM) alone or with a heterobifunctional agent, N-hydroxysuccinimidyl-4-azidobenzoate (HSAB). In both cases five molecular components were revealed, after polyacrylamide gel electrophoresis of the membrane proteins and autoradiography, with the following molecular mass: 196 kDa, 132 kDa, 69 kDa, 45 kDa and 28 kDa. The labeling of 196-kDa, 132-kDa and 45 kDa species was specific in that they could be inhibited by unlabeled SS-28. The major labeled species corresponds to the 132-kDa band and no change in the mobility of this HSAB covalently bound SS-28 receptor was found after addition of dithiothreitol, suggesting that this specific receptor does not contain interchain disulphide bonds. The molecular mass of SS-28 receptors differs markedly from that of guinea-pig pancreatic acinar membranes, where a single 93 kDa protein is identified as a 125I-SS-28 receptor site in comparative experiments. Both the binding kinetics and structural differences sustain the selective action of SS-28 in the endocrine pancreas. PMID- 2897294 TI - Duration of action of bisoprolol after cessation of a 4 week treatment and its influence on pulse wave velocity and aortic diameter: a pilot study in hypertensive patients. AB - A pilot study was performed in hypertensive patients (a) to investigate the duration of blood pressure reduction produced by the new beta blocker bisoprolol (10 mg o.d.) after cessation of a 4 week treatment using non-invasive 24 hour ambulatory blood pressure measurements, (b) to study the effects of the drug on large arteries using non-invasive brachio-radial pulse wave velocity and aortic abdominal diameter measurements 3 hours after the last dose of a 4 week treatment. In comparison with the results obtained before treatment a significant reduction of blood pressure and heart rate was observed up to the 40th hour after treatment was terminated. The finding may be relevant for further evaluation of withdrawal phenomena produced by beta-blocking agents. The antihypertensive effect of bisoprolol was associated with significant decreases in brachio-radial pulse wave velocity (from 10.4 +/- 0.4 to 8.6 +/- 0.4 m s-1) and in aortic abdominal diameter (from 18.2 +/- 1.0 to 17.5 +/- 1.3 mm) indicating an increase in arterial distensibility. Further studies are needed to substantiate these observations and to reveal their mechanisms of action. PMID- 2897295 TI - Bisoprolol: a new beta-adrenoceptor blocking drug. AB - Bisoprolol is a new highly beta 1-selective beta-adrenoceptor blocking drug; it is devoid of intrinsic sympathomimetic effects. Its haemodynamic effects are those expected from beta 1-blockade, heart rate is reduced at rest and on exercise, cardiac output falls and peripherial resistance is increased. Consequent on the beta 1-selectivity there is much greater inhibition of exercise tachycardia compared to inhibition of isoprenaline-induced falls of diastolic blood pressure, in contrast to propranolol. Studies in asthmatics confirm the selectivity of bisoprolol. Bisoprolol has similar solubility in water and organic solvents and predictably therefore about half is excreted by the kidneys unchanged, half metabolized by the liver. Estimates of half-life average about 10 12 h, this is in accord with the therapeutic efficacy of once daily administration. Therapeutic studies have demonstrated the efficacy of bisoprolol in angina pectoris, arrhythmias and hypertension. Comparative studies against atenolol and verapamil in angina suggest similar efficacy. In hypertension a similar antihypertensive effect to nifedipine has been found, while a significantly greater lowering of blood pressure was seen than that obtained with a diuretic. Some studies have also suggested more consistent antihypertensive effect from bisoprolol than atenolol 24 h after administration. This may have been a dosage phenomenon or reflects the longer plasma elimination half-life of bisoprolol, and requires confirmation. Bisoprolol has a favourable side-effect profile. PMID- 2897296 TI - Beta-adrenoceptor blocking drugs in primary and secondary prevention of myocardial infarction. AB - Beta-adrenoceptor blocking drugs reduce mortality by about 20% when used to treat patients in the first 1-3 years after a myocardial infarction. There is suggestive evidence of benefit, averaging about 14% reduction in mortality, when they are used acutely in the coronary crisis. The benefits of beta blockade in primary prevention in patients under treatment for hypertension are less clearly established. Two studies have suggested a benefit but only in non-smoking men, a third study has not confirmed the hypothesis. More evidence is needed. As there is little evidence of comparable benefit with other types of drug, e.g. calcium slow-channel inhibitors, it is reasonable to use beta-blocking drugs in male hypertensives (who should be encouraged to stop smoking in any case), unless there are specific contra-indications. PMID- 2897297 TI - The single dose pharmacokinetics of bisoprolol (10 mg) in renal insufficiency: the clinical significance of balanced clearance. AB - The pharmacokinetics of the beta-blocking agents presently available render some subject to accumulation in renal or hepatic failure. Bisoprolol is one of the beta blockers possessing balanced clearance (both renal and hepatic clearance) which prevents such accumulation even in the case of complete failure of kidneys or liver. The single dose pharmacokinetics of bisoprolol were studied in patients with varying degrees of renal impairment and in healthy controls. Correlations were demonstrated between creatinine clearance and elimination half-life, mean residence time, area under the curve, total clearance and maximum concentration in those with renal dysfunction. The elimination half-life increased by a factor of 1.96 in those with severe renal dysfunction. Because of its balanced clearance, it is unlikely that accumulation of bisoprolol would occur beyond a factor of 2 on dosing to a steady state. The 48 hour plasma levels in the patients on dialysis were similar to those of the patients with severe renal dysfunction. This suggest that accumulation is unlikely, even in end stage renal failure. Bisoprolol may be used safely in patients with renal dysfunction. No adjustment of dose is necessary for those with mild to moderate dysfunction, but in severe or end stage renal failure the dose should not exceed 10 mg once daily. PMID- 2897298 TI - Single oral dose pharmacokinetics of bisoprolol 10 mg in liver disease. AB - The pharmacokinetic profile of an oral single dose of the new cardioselective beta-blocking agent, bisoprolol, was studied in patients with moderate and severe liver disease (Pugh group B and C, respectively) and normal subjects. In patients with liver disease a significant increase in the drug elimination half-life, mean residence time, area under the curve, and time to reach maximum plasma concentration (Tmax) was observed with a significant reduction in the oral clearance compared with the control population. There was significant positive correlation between the Pugh Score (an objective measurement of hepatic dysfunction) and the volume of distribution. The drug was well tolerated although a rise in blood urea and creatinine of over 50% was observed in 4 of 9 patients with severe liver disease. In conclusion, the delayed absorption in these patients results in lower plasma concentrations and indicates that dose adjustment is not necessary but it is recommended that the upper limit for the daily dose should be set at 10 mg; this also applies under chronic dosing of bisoprolol. PMID- 2897300 TI - Comparison of the effects of two doses of bisoprolol on exercise tolerance in exercise-induced stable angina pectoris. AB - Recently, bisoprolol has been investigated regarding its effects on exercise tolerance and the duration of action in patients with coronary heart disease (CHD) following single oral administration. It appears, however, that the extent of effects of 5 mg bisoprolol is not fully established yet. Therefore, the effects of 5 and 10 mg bisoprolol and the duration of action were assessed in 12 patients (10 male, 2 female; mean age 60.2 years) with stable angina pectoris due to CHD after repeated administration. Patients were given 5 or 10 mg bisoprolol once daily for 2 weeks according to a double-blind, randomized cross-over design. At entry one exercise tolerance test (ETT) served as baseline measurement and following each treatment period ETTs were performed before (24-hour value) and 3 hours after tablet intake. Exercise capacity (in W X min) was calculated until the onset of angina, 0.1 mV ST-segment depression and at peak exercise. Compared to baseline all workload values during active therapy were significantly improved (P less than or equal to 0.05) except for the workload till onset of angina with bisoprolol 5 mg at 24 hours. The effects at 3 hours were significantly stronger than those after 24 hours for both dosages. Significantly stronger effects were observed 3 hours as well as 24 hours after intake during treatment with 10 mg compared to 5 mg: at peak exercise on heart rate (P less than or equal to 0.05) and exercise capacity (P less than or equal to 0.01), at identical workload on heart rate (P less than or equal to 0.01) and rate-pressure product (P less than or equal to 0.01). It was found that bisoprolol 5 mg once daily leads to therapeutic effects with a clearly maintained duration of action over 24 hours, but further increase of peak exercise capacity may be achieved with 10 mg. PMID- 2897302 TI - Electrophysiological effects of bisoprolol. AB - The aim of this study was the electrophysiological evaluation of bisoprolol, a new highly cardioselective beta blocker, void of intrinsic sympathomimetic activity and without significant membrane stabilizing action. 10 patients (4 males and 6 females, mean age 67.5 years) with cardiac arrhythmias or syncopes of undetermined origin underwent His bundle recording with incremental as well as programmed atrial and ventricular pacing in an electrophysiological study. Electrophysiological parameters were measured at basal conditions and at 15 and 30 minutes after the infusion of bisoprolol 5 mg (for patient 1 to 5) and 10 mg (for patient 6 to 10). All electrophysiological parameters were within normal range at basal evaluation. Bisoprolol prolongs significantly sinus cycle length, corrected sinus node recovery time, AH interval, cycle length inducing AV-node block, effective and functional refractory periods of the AV-node. All these parameters remained within normal limits and were modified to about the same extent by 5 and 10 mg of the drug. No drug-related changes of QT interval were observed. Bisoprolol have been confirmed to have strictly beta-blocking properties. PMID- 2897299 TI - Reduction of exercise tachycardia in man after propranolol, atenolol and bisoprolol in comparison to beta-adrenoceptor occupancy. AB - In a double blind, placebo controlled study, propranolol (240 mg), atenolol (200 mg) or bisoprolol (100 mg) were administered as a single oral dose to groups of 6 healthy male volunteers. Exercise tachycardia was monitored for 84 hours after administration of the drugs to monitor beta blockade in vivo. Plasma samples drawn in parallel with these effects were used to detect beta 1- or beta 2 adrenoceptor occupancy in two subtype selective in vitro receptor binding assays. Reduction of exercise tachycardia parallels beta 1-adrenoceptor occupancy. Furthermore, at comparable beta 1-adrenoceptor occupancy, less beta 2 adrenoceptor occupancy was observed after bisoprolol than after atenolol. The latter finding is in agreement with the two-fold higher beta 1/beta 2-selectivity ratio of bisoprolol (75-fold) versus atenolol (35-fold). It is concluded, that beta blockade observed via the reduction of exercise tachycardia can be delineated from the in vitro occupancy of beta 1-adrenoceptors by an antagonist present in plasma samples. PMID- 2897301 TI - Changes in regional blood flows and myocardial performance after administration of bisoprolol to pigs. AB - The cardioselective beta-adrenoceptor antagonist bisoprolol (4-1024 micrograms kg 1) caused in anaesthetized open-chest pigs a dose-dependent decrease in cardiac output, which was primarily due to a negative chronotropic action as heart rate decreased more than stroke volume. The decrease in stroke volume apparently resulted from a negative inotropic action of the drug, reflected by a decrease in max LV dP/dt in animals both with and without atrial pacing. A mild increase in systemic vascular resistance prevented serious hypotension. Pulmonary artery pressure was not affected, as pulmonary vascular resistance increased although the increase was statistically significant only with the highest concentration. The dose-related decreases in left ventricular blood flow were equally distributed over all myocardial layers and were the consequence of the reduced metabolic needs of the myocardium. Cerebral blood flow was well preserved but the changes in blood flow to some other organs and tissues (kidneys, stomach and skeletal muscle) paralleled that in cardiac output. The systemic haemodynamic effects of bisoprolol (16-1024 micrograms kg-1; i.v.) in conscious pigs resembled closely those observed in anaesthetised animals and were similar to those exerted by propanolol (25-300 micrograms kg-1; i.v.) in the same preparation. The effectiveness of bisoprolol and propranolol in antagonizing isoprenaline-induced changes in heart rate and max LV dP/dt were, however, markedly different. While propranolol inhibited both parameters to the same extent, bisoprolol was more effective in inhibiting max LV dP/dt than heart rate responses in conscious animals, probably due to beta 1-adrenoceptor selectivity. PMID- 2897304 TI - Comparison of pharmacokinetic properties of beta-adrenoceptor blocking drugs. AB - Beta-adrenoceptor blocking drugs can be characterised by their pharmacokinetic properties. One of the most important factors appears to be lipid solubility. Lipophilic beta-adrenoceptor antagonists, such as propranolol, oxprenolol and metoprolol, are cleared by the liver and undergo hepatic 'first-pass' metabolism. This results in low bioavailability, substantial interpatient variability in 'steady-state' plasma drug concentrations, rapid elimination half-lives and the possibility of drug interactions with other drugs such as pentobarbitone and cimetidine which affect hepatic enzymes. In addition, lipid soluble drugs are distributed widely within the body and penetrate the brain easily and rapidly. This may result in centrally mediated adverse effects such as vivid dreams. In contrast, the more water-soluble beta-adrenoceptor blocking drugs, such as atenolol, sotalol and nadolol, are cleared by the kidney unchanged. They show less interpatient variation in plasma levels, have longer elimination half-lives and do not interact with drugs affecting hepatic enzymes. They penetrate the central nervous system less easily and cause less central side-effect. Between these two extremes, there are several drugs like betaxolol, bisoprolol and pindolol, which are cleared partly by the liver and partly by the kidney. Their clearance is only altered by severe renal or hepatic disease, and they do not appear to interact with enzyme inducers or inhibitors. PMID- 2897303 TI - Effects of bisoprolol on local vascular resistance. AB - Changes in systolic and diastolic blood pressure, heart rate, arterial blood flow and vascular resistance in the arm and in the leg were investigated in 9 healthy volunteers (22-40 years) after oral dosing with bisoprolol 10 mg, propranolol 40 mg, and placebo in a randomized double-blind cross-over study. Arterial blood flow and vascular resistance were determined in brachial and femoral arteries with unimpeded circulation, after exclusion of the hand or foot by placing a tourniquet on the wrist or ankle, and during post-ischaemic hyperaemia. Distal arterial occlusion allows one to isolate a predominantly muscular circulation in the forearm or, to a lesser extent, in the leg. Both active drugs induced a significant fall in heart rate and systolic blood pressure versus placebo with no significant difference between the drugs. Brachial and femoral flow rates were reduced by both drugs probably due to a fall in cardiac output, but the two beta blockers produced different effects on vascular resistance: propranolol significantly increased brachial vascular resistance compared with placebo and bisoprolol, both during unimpeded circulation and during occlusion of the hand by a wrist tourniquet. Bisoprolol had no influence on brachial vascular resistance. Both drugs induced small increases in femoral vascular resistance. The different action on local vascular resistance in the brachial artery territory could be interpreted as the expression of the high beta 1 selectivity of bisoprolol leaving the vascular beta 2 receptors unopposed, whereas non-selective propranolol acts on both beta-adrenoceptor subtypes. PMID- 2897305 TI - Bisoprolol versus hydrochlorothiazide plus amiloride in essential hypertension, a randomized double-blind study. AB - Beta blocker monotherapy is often considered to be inadequate in essential hypertension. It was the aim of this study to compare the antihypertensive activity of the new betablocker bisoprolol with the diuretic combination: hydrochlorothiazide plus amiloride. Forty hypertensive patients (DBP 95-120 mmHg) were enrolled in the study, of which 34 were evaluable for efficacy. The patients were, under double-blind conditions, randomly allocated to receive 10 mg bisoprolol (B) or 50 mg hydrochlorothiazide plus 5 mg amiloride (HA) as single daily doses for 30 days. Patients whose DBP had been normalized (less than or equal to 90 mmHg) after 30 days (D 30) continued the monotherapy for another 30 days. Patients whose DBP remained over 90 mmHg were, under single-blind conditions, kept on their initial treatment but received in addition the alternative drug for another 30 days (D 60). Blood pressure measurements were performed 24 hours after drug intake. The two groups comprising 17 patients each were comparable with regard to the patients' characteristics and baseline blood pressure values. After 30 days of treatment supine SBP, DBP and HR were significantly more reduced with B than with HA. The mean reduction of DBP was 16.8 +/- 8.0 mmHg with B and 8.4 +/- 6.4 mmHg with HA (P less than 0.002). After 30 days of monotherapy, blood pressure was within the normal range in 15/17 (88.2%) patients treated with B but in only 4/17 (23.5%) patients treated with HA (B vs HA: P less than 0.001). In the B group, there was a further slight decrease in SBP, DBP and HR during the second 30 day period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897306 TI - Adrenergic arrhythmogenicity. PMID- 2897308 TI - Direct application of a guanylate cyclase activator lowers intraocular pressure. PMID- 2897307 TI - Desenkephalin-gamma-endorphin and neuroleptics counteract the DP-7-ATN-induced hypomotility after intra-accumbens treatment. AB - Injection of the selective presynaptic dopamine agonist N,N-dipropyl-7-hydroxy-2 aminotetralin (DP-7-ATN, 1 fg to 1 microgram) into the nucleus accumbens decreased motor activity. The reduction of motor activity was reversed by pretreatment with haloperidol (10 pg), (-)-sulpiride (10 pg) or desenkephalin gamma-endorphin (DE gamma E) (100 pg). These results support the hypothesis that DE gamma E may interfere with presynaptically located D-2 dopamine receptor systems in the nucleus accumbens. Furthermore, the use of DP-7-ATN in the described test procedure might be a useful model for testing novel neuroleptic compounds in vivo. PMID- 2897309 TI - Evidence for ATP as a cotransmitter in dog mesenteric artery. AB - Contractile responses of the dog mesenteric artery were obtained (after removal of endothelium) to transmural stimulation of the perivascular nerves and to exogenous application of ATP, noradrenaline, dopamine, 5-hydroxy-tryptamine and high potassium solution. The alpha-adrenoceptor antagonists prazosin and phentolamine preferentially reduced the response to noradrenaline and the secondary phase of the biphasic contractile response to nerve stimulation, whilst the addition of alpha, beta-methylene-ATP, which selectively desensitizes P2 purinoceptors, reduced only the contractions to ATP and the portion of the nerve mediated response which was resistant to the alpha-adrenoceptor antagonists. The responses to nerve stimulation were reduced by the selective P1-purinoceptor agonist 2-chloroadenosine, and its effect was reversed by the P1-purinoceptor antagonist 8-phenyltheophylline. These results suggest that in dog mesenteric artery part of the response to sympathetic nerve stimulation is mediated by ATP acting on P1-purinoceptors on the arterial smooth muscle, and that P1 purinoceptors on the sympathetic nerve terminal can inhibit release of the neurotransmitters. PMID- 2897310 TI - Effect of uncouplers of oxidative phosphorylation on transmitter release in dystrophic mice. AB - Intracellular recording was used to study the effect of uncouplers of oxidative phosphorylation on miniature endplate potentials (m.e.p.p.s) in skeletal muscles from dystrophic mice and their clinically normal littermates. Control m.e.p.p. frequency in muscles from dystrophic mice was not significantly different from normal. In the presence of the inhibitors 2,4-dinitrophenol (10(-4) M) or guanidine (5 X 10(-3) M) m.e.p.p. frequency was increased less in muscles from dystrophic mice than that in muscles from normal littermates. In contrast, raising the extracellular calcium concentration, depolarising nerve terminals with potassium or motor nerve stimulation all caused a similar increase in m.e.p.p. frequency in normal and dystrophic muscles. It is suggested that there is a difference in the way in which calcium is stored in dystrophic nerve terminals but that their ability to regulate free calcium is normal. PMID- 2897311 TI - Regulation of tyrosine hydroxylase mRNA levels in rat pheochromocytoma PC12 cells by cell-cell contact. AB - It has previously been shown that cell density increases the specific enzyme activity of tyrosine hydroxylase (TH) in cultures of PC12 cells. The difference in TH activity was shown to be due to cell-cell contact rather than to diffusible factors released by the PC12 cells (C. Lucas, D. Edgar, and H. Thoenen (1979) Exp. Cell Res. 121, 79-86). We have extended these studies and demonstrated that TH is regulated at the transcriptional level. Cells were harvested from confluent high-density cultures and replated at either low (2 x 10(4) cells/cm2) or high density (5 x 10(5) cells/cm2). At low density, the mRNATH and TH enzyme activity decreased to low levels within several hours. The decrease in TH activity resulting from the loss of cell-cell contact appears to be an active process, as it occurs much more rapidly than would be expected from the turnover rate of the protein in cells cultured continuously at high density. In contrast to low density cultures the mRNATH and TH activity levels in replated high-density cultures decreased only slightly and then increased four fold at the mRNATH and five fold at the TH activity levels as compared to low-density cultures 2 days after replating. The increase in mRNATH preceded the increase in TH activity by 1 day. Since alpha-amanitin inhibited the increase in TH levels, we conclude that cell-cell contact regulates TH in PC12 cells at the transcriptional level. PMID- 2897312 TI - [Neuropeptides and the regulation of the nervous system secretion]. PMID- 2897313 TI - [Drug therapy of pituitary neoplasms]. PMID- 2897314 TI - Drugs in dentistry. Opioid analgesics. PMID- 2897316 TI - [Visceral larva migrans: a probable cause of increase in gamma glutamyltransferase]. PMID- 2897315 TI - Induction of nesidioblastosis will reverse diabetes in Syrian golden hamster. AB - Nesidioblastosis, which is the formation of new islets and the differentiation of cells within the islets, represents part of the spectrum of hyperfunctioning states of the islets of Langerhans at the clinical level. Nesidioblastosis in the Syrian golden hamster can be induced by wrapping the head of the pancreas with cellophane tape. Ligation of the duct is not involved, and acinar cell atrophy does not occur. The purpose of this study was to determine whether the induction of nesidioblastosis could be used as a means of reversing streptozocin-induced diabetes. Outbred hamsters (n = 32), 8 wk of age, were rendered diabetic by treatment with 40 mg/kg i.p. streptozocin, administered daily for 3 days. Four days later, 16 animals chosen at random underwent laparotomy with cellophane wrapping of the pancreas. Before surgery, the serum glucose and insulin levels (means +/- SE) in the unoperated control animals (389.0 +/- 18.6, 33.9 +/- 3.8) did not differ from those in the animals awaiting the operation (373.2 +/- 18.6, 37.9 +/- 3.8). After 7 wk, 50% of the operated animals had serum glucose and insulin levels that were normal, compared to only 12% of the unoperated control animals (chi2 = 5.53, P less than .05). Islets from normoglycemic operated animals were characterized by increased numbers, including many small islets, positive immunoreactive insulin staining, and minimal vacuolation of cells. Islets from hyperglycemic operated hamsters and from the unoperated control animals were decreased in number and generally larger in size, demonstrated little or no immunoreactive insulin staining, and exhibited marked vacuolation of cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897317 TI - Intracerebroventricular pressure inhibits gastric antral and duodenal contractility but not acid secretion in conscious rabbits. AB - Acute nausea characteristically accompanies head injury or increased intracranial pressure, or both. The etiology of this symptom is unclear. We studied the effect of increased intracranial pressure on gastric antral and duodenal contractility and gastric acid secretion in conscious rabbits. Intracerebroventricular pressure was maintained at 3, 8, or 13 cmH2O using normal saline perfused into the lateral cerebral ventricle and gastric antral and duodenal contractility was monitored using chronically implanted strain gauge force transducers. Gastric acid secretion was measured in a separate group of rabbits with chronically implanted gastric cannulas. Increased intracerebroventricular pressure (13 cmH2O) resulted in an immediate suppression of the amplitude of gastric and duodenal contractions by greater than 80% and greater than 60%, respectively. After normalization of intracerebroventricular pressure, the contractile pattern returned to basal levels. Intravenous bolus injection of bethanechol reversed the suppression of gastric antral contractility induced by increased intracranial pressure. Increased pressure for 2 h did not modify gastric acid output as compared with normal pressure controls, whereas atropine significantly inhibited and histamine stimulated gastric acid secretion in the same animals maintained at normal pressure. These results demonstrate that acutely increased intracranial pressure rapidly and reversibly inhibits gastric and duodenal motor function in conscious rabbits. PMID- 2897318 TI - Molecular cloning and characterization of homeo-box-containing genes from Atlantic salmon. AB - As the most primitive group among vertebrates, fish might serve as a model system when studying the genetic regulation of embryogenesis in higher animals. To identify genes important for early development, we have constructed a genomic library from Atlantic salmon (Salmo salar) and screened it with homeobox containing probes from Drosophila melanogaster. Five different salmon homeoboxes were isolated. Two of these were located in the same clone, separated by only 7.5 kb. This demonstrates the presence of clustered homeobox genes in fish. The two clustered homeoboxes were sequenced and shown to be closely related to the ANT C/BX-C class of Drosophila, being about 80% homologous to the Ultrabithorax gene (Ubx) homeobox. One of the clustered genes appears to be the salmon equivalent of the mouse Hox-2.1 gene, indicating that some of the vertebrate homeobox containing genes are conserved in evolution. A more diverged homeobox that shares only 60% homology with Ubx, was also sequenced. In analogy to Drosophila, therefore, the salmon genome contains more than one class of homeoboxes. In addition, Northern-blot experiments demonstrated that two of the homeobox genes are expressed in salmon embryos, suggesting their importance for proper development. PMID- 2897319 TI - [Drug therapy of dysmenorrhea]. PMID- 2897320 TI - [Drug therapy of pain]. PMID- 2897321 TI - [Effect of tiapride on the activity of neuroleptics and other kinds of drugs in mice and rats]. AB - Tiapride is a central dopamine receptor specific antagonist, and it has a benzamide chemical structure. This drug is very useful for the treatment of dyskinesia and such abnormal behaviors as delirium and psychomotor excitation in patients with arteriosclerosis. Most of these patients are elderly and generally suffer from other diseases. Since they are apt to be treated with several drugs for such diseases, the effect of tiapride in combination with various kinds of drugs was examined in rats and mice. Tiapride significantly potentiated the catalepsy-inducing effect of haloperidol and chlorpromazine in rats and tended to potentiate the muscle relaxing effect of diazepam at the highest dose in mice. Conversely, tiapride did not enhance or diminish the hypnotic effect of bromvalerylurea, the anticholinergic activity of trihexyphenidyl, the diuretic effect of bromvalerylurea, the anti-cholinergic activity of trihexyphenidyl, the diuretic effect of trichloromethiazide, or the anti-diabetic effect of glibenclamide. Our findings suggest that tiapride should be used with care in patients taking neuroleptics, but can be used freely in patients on other kinds of drugs. PMID- 2897322 TI - [Hypertension therapy of first choice. 3d International Nitrendipine Symposium. 10 February 1988, Basel]. PMID- 2897323 TI - [Hemodynamics and ventricular function in dilated cardiomyopathies following administration of the new beta-blocker ridazolol]. AB - Recent reports in the literature indicate that beta-blockade may improve survival in patients with dilated cardiomyopathy (DCMP). This goal can obviously not be attained if the beta-blocker employed effects deleterious actions on the left ventricular function or hemodynamics. Accordingly, to assess the suitability of the new beta-blocker ridazolol for use in this regard, in nine patients with DCMP NYHA class II/III, studies were performed (by means of balloon-tipped pulmonary artery catheter and radionuclide ventriculography) at rest and during exercise prior to and one hour after oral administration of a 40 mg-dose of the agent. At rest, there was a decreasing tendency in systolic blood pressure from 123 +/- 18.5 mm Hg to 113 +/- 15.2 mm Hg and heart rate from 94 +/- 19 beats/min to 83 +/ 17 beats/min. Pulmonary capillary wedge pressure was not significantly altered at 16.2 +/- 7.9 mm Hg and 17.1 +/- 8.4 mm Hg, respectively. Ejection fraction remained unchanged with 29 +/- 14%. The slight decrease in cardiac output from 5.1 +/- 1.3 l/min to 4.5 +/- 1.3 l/min was not significant. During exercise, there were also decreasing tendencies in the heart rate from 128 +/- 21 beats/min to 102 +/- 22 beats/min and the systolic blood pressure from 148 +/- 20.5 mm Hg to 141 +/- 18.4 mm Hg. Essentially unchanged were the pulmonary capillary wedge pressure (26.1 +/- 7.2 mm Hg/27.8 +/- 5.0 mm Hg) and ejection fraction (30 +/- 10%/27 +/- 8%) during exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897325 TI - Evidence for the release of somatostatin from human thyroid. PMID- 2897324 TI - Insulin-stimulated protein synthesis in submandibular acinar cells: interactions with adrenergic and cholinergic agonists. AB - The effects of insulin and secretory agonists on amino acid incorporation into submandibular gland proteins were studied using isolated acinar cell aggregates. Insulin stimulated the incorporation of 3H-leucine into TCA-precipitable proteins in a rapid, dose-dependent manner (half-maximal response at 1 nM). Isoproterenol, a beta-adrenergic agonist, also stimulated amino acid incorporation, and this effect was mimicked by both dibutyryl cAMP and IBMX, a phosphodiesterase inhibitor. Although insulin further stimulated incorporation in the presence of isoproterenol and IBMX, no additional increase in the rate of synthesis was observed after stimulation by dibutyryl cAMP. High concentrations of carbamylcholine, a cholinergic agonist, inhibited both basal and insulin stimulated incorporation. At low concentrations, however, carbamylcholine stimulated synthesis, and the effects of insulin and carbamylcholine were additive. A23187, a calcium ionophore, also inhibited 3H-leucine incorporation and insulin stimulation, but in contrast to carbamylcholine, low concentrations of A23187 neither inhibited nor enhanced the rate of synthesis. Thus, protein synthesis in the rat submandibular gland is regulated by both insulin and neurotransmitters. Whereas beta-adrenergic stimulation appears to be mediated through cAMP, the intracellular signals mediating the actions of insulin and cholinergic agonists remain to be elucidated. PMID- 2897327 TI - Human T-cell leukemia/lymphoma viruses: ATL and AIDS. PMID- 2897326 TI - Characterization of a CD11c-reactive monoclonal antibody (HC1/1) obtained by immunizing with phorbol ester differentiated U937 cells. AB - A mouse monoclonal antibody (HC1/1) specific for a differentiation marker of human monocytes and granulocytes has been generated by using as immunogen the monocytic cell line U937 differentiated with phorbol esters. This differentiation antigen has been characterized as the p150/95 member of the CD11 family of glycoproteins by cellular distribution studies, immunoprecipitation and competition experiments with MAb 3.9 specific for the CD11c antigen. Immuno alkaline phosphatase staining of normal tissue sections with the HC1/1 MAb demonstrated that the CD11c antigen is a useful macrophage marker. Furthermore, the MAb HC1/1 stains specifically populations of macrophages on skin and lymph node sections from different pathologies such as Sarcoidosis, Granuloma annulare, Lepromatous leprosy and Toxoplasmosis. PMID- 2897328 TI - Preoperative beta blockade for PDA ligation. PMID- 2897329 TI - Generation of L3T4-/Ly-2- T cells in Peyer's patches of mice treated with monoclonal antibody against helper T cells. AB - The effect of in vivo administration of anti-L3T4 monoclonal antibody on the generation of an L3T4-/Ly-2- (CD4-/CD8-) population of Thy-1.2+ cells was examined in Peyer's patches of mice by two-color flow cytometry. Female BALB/c mice aged 8 wk were given 4-6 weekly injections of either anti-L3T4 (1 mg/wk) or phosphate-buffered saline (control group), and dispersed Peyer's patch cells analyzed for the presence and absence of L3T4 and Ly-2 on Thy-1.2+ cells. In anti L3T4 treated mice, L3T4-/Ly-2- T cells accounted for 25-30% of the Thy-1.2+ cells, whereas in control mice these cells represented only 3-4% of the T cells. The remaining 70-75% of the Thy-1.2+ cells after anti-L3T4 treatment were Ly-2+ and not L3T4+. The L3T4-/Ly-2- population of Thy-1.2+ cells is a novel subset which has not been previously found in Peyer's patches and is amplified when helper T cells are depleted. PMID- 2897331 TI - RFLP analysis of SLA class I genotypes in Duroc swine. PMID- 2897332 TI - Amoebicidal activity of nitrovinylindole. PMID- 2897330 TI - Molecular characterization and genetic mapping of class I and class II MHC genes of the domestic cat. AB - The major histocompatibility complex (MHC) of the domestic cat has been poorly characterized to date, primarily because of numerous difficulties in the preparation of allotypic sera. We present here a comparative analysis of class I and class II genes in domestic cat populations using molecular probes of the MHC from man and mouse. The cat possesses a minimum of 20 class I loci and 5 class II genes per haploid genome. Class I genes of the domestic cat expressed limited restriction fragment length polymorphism. The average percent difference of the size of DNA fragments between individual cats was 9.0%, a value five times lower than the value for mice, but comparable to the human DNA polymorphism level. Class I and class II genes were both genetically mapped to feline chromosome B2 using a panel of rodent x cat somatic cell hybrids. Since feline chromosome B2 is syntenically homologous to human chromosome 6 and mouse chromosome 17, these results affirm the linkage conservation of the MHC-containing linkage group in the three mammalian orders. PMID- 2897333 TI - Isolation and nucleotide sequence of the F17-A gene encoding the structural protein of the F17 fimbriae in bovine enterotoxigenic Escherichia coli. AB - The genetic determinant for production of the fimbrial F17 adhesive antigen was isolated from a bovine enterotoxigenic Escherichia coli strain. The F17-A gene, coding for the structural component of the F17 fimbrial adhesin, was cloned and sequenced. An open reading frame of 540 base pairs encoding a polypeptide of 180 amino acids, of which the NH2-terminal 21 residues are characteristic of a signal sequence, has been characterized. The mature protein lacks histidine, methionine, and tryptophan. A possible promoter and ribosome binding site as well as a possible site for termination of transcription are proposed. An important homology of the F17-A protein with fimA and papA fimbrial proteins was found. The N-terminal sequence of the mature F17-A pilin is extremely similar to the N terminal sequence of the G fimbriae identified on human pyelonephritogenic E. coli strains. PMID- 2897334 TI - Phorbol esters specifically enhance the cytolytic activity of Entamoeba histolytica. AB - Entamoeba histolytica causes invasive amebiasis by lysis of host tissue and inflammatory cells. The in vitro cytolysis of target Chinese hamster ovary (CHO) cells by axenic E. histolytica trophozoites (strain HM1:IMSS) is a calcium- and phospholipase A-dependent event initiated by the binding to the target cell of the galactose-inhibitable surface lectin of the parasite. We utilized phorbol esters as a probe to determine whether an amebic protein kinase C has a role in the cytolytic event. The addition of phorbol 12-myristate 13-acetate (PMA) at 10( 6) or 10(-7) M resulted in a greater than twofold enhancement of amebic killing of target CHO cells over 30 min (P less than 0.01). Prior exposure of only the amebae, but not the CHO cells, to PMA produced a similar effect (P less than 0.01). The inactive analog 4-alpha-phorbol had no effect on amebic killing of CHO cells. The PMA-mediated enhancement of amebic cytolysis persisted for up to 60 min after a 5-min exposure; however, after a 30-min exposure to PMA (10(-6) M) there was no augmentation of amebic killing of CHO cells. PMA (10(-6) M) did not promote adherence of parasites to CHO cells but did enhance amebic cytolysis of previously adherent target cells (P less than 0.01). Sphingosine, a specific inhibitor of protein kinase C, abolished both the PMA-stimulated and the basal cytolytic activity of E. histolytica. PMA enhanced CHO cell cytolysis by the less virulent wild-type strain H-303:NIH (P less than or equal to 0.02) but did not augment the activity of the less virulent strain H-200:NIH or two avirulent clones of HM1 (L6 and C919). In summary, these experiments with the phorbol esters and sphingosine as probes to modulate the activity of protein kinase C indicate participation of a parasite protein kinase C in the cytolytic activity of virulent, axenic E. histolytica trophozoites and thus in the pathogenesis of amebiasis. PMID- 2897336 TI - Role of pili in adhesion of Pseudomonas aeruginosa to human respiratory epithelial cells. AB - The ability of pili from Pseudomonas aeruginosa K (PAK) to act as an adhesin to human respiratory epithelial cells was examined using an in vitro adhesion assay. Equilibrium analysis of PAK binding to human buccal epithelial cells (BECs) and tracheal epithelial cells (TECs) by means of a Langmuir adsorption isotherm revealed that the maximum numbers of binding sites per epithelial cell (N) were 255 for BECs and 236 for TECs, with apparent association constants (Ka) of 2.8 x 10(-9) and 5.8 x 10(-9) ml/CFU, respectively. Trypsinization of the BECs before the binding assay increased N to 605 and decreased the Ka to 1.7 x 10(-9) ml/CFU. Addition of homologous pili to the binding assay with BECs or TECs or the addition of anti-pilus Fab fragments inhibited PAK adherence. Binding of purified pili to BECs was shown to reach saturation. Purified pili and PAK competed for the same receptor on the BEC surface. Further, by using peptide fragments of PAK pilin (derived from the native pili or produced synthetically) in the binding assay for PAK to BECs, we have presumptively identified the pilus binding domain in the C-terminal region of the pilin and shown that the C-terminal disulfide bridge is important in maintaining the functionality of the binding domain. PMID- 2897337 TI - Antimicrobial susceptibility of Bordetella pertussis (Part I). AB - In this review of the literature data are collected from the more recent studies on the susceptibility of Bordetella pertussis to penicillins, cephalosporins, other beta-lactam antibiotics, aminoglycosides, tetracyclines, erythromycin, josamycin, co-trimoxazole and various other antibiotics. The methods of susceptibility testing of B. pertussis are discussed and suggestions for standardization are made. PMID- 2897338 TI - Effect of simulated orchiopexy on spermatogenesis in the dog. AB - The poor fertility after orchiopexy can be due either to the previously prolonged high abdominal temperature, to surgical trauma or to congenitally malformed or dissociated testis and epididymis. In order to test whether manipulation of the testis and the spermatic cord in juvenile dogs causes damage to the seminiferous epithelium after puberty, orchiopexy was performed stepwise in 31 normal young dogs. In four dogs, in which traction to the proper testis ligament or biopsy was carried out, a significantly lower relative testis weight was found, together with impaired differentiation of the seminiferous epithelium. From these experiments it was clear that surgical procedures in the inguinal and scrotal region do not necessarily affect the development of the seminiferous epithelium in the dog. However, trauma to the vaginal tunic seemed to be crucial, causing damage to the differentiation of the seminiferous epithelium. PMID- 2897339 TI - Glutathione, L-glutamic acid and gamma-glutamyl transpeptidase in the bull reproductive tissues. AB - The distribution of glutathione (GSH), L-glutamic acid (Glu) and gamma-glutamyl transpeptidase (gamma-GT) was studied in bull reproductive organs and fluids. Glutathione, the physiological substrate of gamma-GT, was localized specifically by a fluorescence method in the testis, epididymis and spermatozoa. Of the reproductive tissues, the testis, caput epididymis and ampulla had the highest levels of GSH, but it was also present in seminal fluid. Washed caput epididymal sperm had three times the GSH content of cauda epididymal or ejaculated sperm. In spermatozoa, GSH displayed maximal staining in the midpiece and tail regions. The highest levels of gamma-GT were encountered in the epididymis. The concentration of Glu was also high in the epididymis. Its formation may be due to the hydrolytic activity of gamma-GT, which, in addition, may have an important role in the transfer of Glu residues to reactive groups on the sperm surface. PMID- 2897335 TI - Relationship of free intracellular calcium to the cytolytic activity of Entamoeba histolytica. AB - Entamoeba histolytica adherence and destruction of host cells is required for in vivo pathogenicity; amebic in vitro adherence is mediated by a galactose- or N acetyl-D-galactosamine-inhibitable surface lectin (Gal/GalNAc adherence lectin). Free intracellular Ca2+ concentration [( Ca2+]i) was measured in living amebae and target cells during amebic cytolysis of Chinese hamster ovary (CHO) cells and human polymorphonuclear neutrophils by utilizing the Ca2+ probe Fura-2 and computer-enhanced digitized microscopy. Motile E. histolytica trophozoites had oscillatory increases in [Ca2+]i in head or tail regions; however, there was no increase in regional or total amebic [Ca2+]i upon contact with a target CHO cell. Target CHO cells and polymorphonuclear neutrophils demonstrated marked irreversible increases in [Ca2+]i within 30 to 300 s following contact by an ameba (P less than 0.01); increased [Ca2+]i preceded the occurrence of nonspecific surface membrane permeability and death of the target cell. Target CHO cells contiguous on a monolayer to a cell contacted by an ameba experienced a rapid but reversible rise in [Ca2+]i (P less than 0.01) and were not killed. Galactose (40 mg/ml) totally abrogated the rise in target CHO cell [Ca2+]i that followed contact by amebae (P less than 0.01); immunoaffinity-purified amebic Gal/GalNAc adherence lectin (0.25 micrograms/ml) induced a rapid and reversible rise in CHO cell [Ca2+]i (P less than 0.01) which was inhibited by galactose. Amebic [Ca2+]i was not elevated following parasite adherence to target cells; a rapid and substantial rise in target cell [Ca2+]i occurred which was mediated, at least in part, by the Gal/GalNAc adherence lectin of the parasite and led to the death of target cells. PMID- 2897341 TI - Influence of cyclosporin A on growth of an acute T-cell leukaemia in PVG rats. AB - Our objective was to examine the effect of cyclosporin A (CsA; 25 or 12.5 mg/kg) on growth of an acute (Roser) T-cell leukaemia in male PVG rats. The leukaemic blasts were shown (by immunocytochemical analysis) to have a mature, T-helper cell phenotype, i.e., OX-19 (CD5) +/- , W3/25 (CD4)+, OX44+, MHC-class I+, OX 26+, corresponding to a population comprising 5% of normal rat medullary thymocytes. Animals received 20 X 10(3) viable tumour cells intramuscularly (day 0) and were given either CsA (25 or 12.5 mg/kg) or drug vehicle by gavage from day 0 or day 14, by which latter time leukaemic blasts normally appeared in the circulation. Administration of the higher dose of CsA from day 0 or day 14 significantly delayed the appearance of leukaemic cells in the peripheral circulation, whereas treatment with 12.5 mg/kg was without significant effect. CsA whole blood levels on day 17 were twice as high in leukaemic rats as in normal controls. Leukaemic infiltration of the spleen and the liver was reduced on day 17 after 25 mg/kg CsA, but no such effect was observed in lymph nodes or kidneys. A heterogeneous, host "reactive" cell population, which developed in response to the leukaemia, was inhibited by CsA, indicating that the effect of the drug was probably not mediated by host defence mechanisms. In CsA-treated leukaemic animals, there was biochemical evidence of synergistic impairment of glomerular and tubular function. PMID- 2897340 TI - Serial transplantation of an HTLV-I-transformed hamster lymphoid cell line into hamsters. AB - A hamster lymphoid cell line, HCT-2, transformed by human T-cell leukemia virus type I (HTLV-I) was serially transplanted for 9 passages in newborn hamsters. A total of 34 newborn hamsters inoculated intraperitoneally (i.p.) with 0.2-2 X 10(7) HCT-2 cells developed fatal lymphomas with dissemination to various organs within 5-10 days. The growth of i.p. inoculated HCT-2 cells was found to be dependent on the age of recipients: all 21 suckling hamsters inoculated when aged 5-10 days succumbed to disseminated lymphomas within 6-7 days, while 4 of 12 older hamsters inoculated at the age of 15-25 days developed less extensive disease with signs of tumor regression. To investigate the effect of immunosuppression on host resistance, 3 adult hamsters treated with anti thymocyte serum were inoculated i.v. with 2-4 X 10(7) HCT-2 cells; all 3 developed fatal leukemias in 5-7 days. Irrespective of whether HCT-2 cells were inoculated into newborn, suckling, or adult hamsters, histopathological findings were similar, with frequent involvement of liver, spleen, lungs, kidneys, lymph nodes, blood, and bone marrow. Cells harvested from tumors and peripheral blood of some tumor-bearing hamsters could be readily recultured as cell lines. Chromosome analysis and Southern blot hybridization showed that tumors were caused by growth of HCT-2 cells. PMID- 2897343 TI - Absence, or low expression, of leukocyte adhesion molecules CD11 and CD18 on Burkitt lymphoma cells. AB - Leukocyte adhesion to cells is mediated by the cell-surface glycoprotein complex CD11a-c/CD18 and, in some cases, the glycoprotein gp84. The process is associated with leukocyte activation and modulates lymphocyte proliferation and maturation. Epstein-Barr virus (EBV)-transformed normal B lymphocytes give rise to lymphoblastoid cell lines (LCLs) which grow as large clusters mediated by adhesion molecules. In contrast, newly explanted EBV-infected Burkitt lymphoma (BL) cells usually grow as single cells or as loose clusters. We now report that EBV positive- and EBV-negative BL lines lack the adhesive protein complex, or have only low levels of it, whereas LCLs, representing various stages of B lymphocyte development, contain considerably higher amounts, as measured by immunofluorescence flow cytometry and immunoprecipitation. The level of gp84 expression is of the same magnitude in both types of cells. PMID- 2897342 TI - Differential effects on expression of IL-2 receptors (p55 and p70) by the HTLV-I pX DNA. AB - Abnormal expression of the low-affinity receptor for interleukin-2 (IL-2R) is a characteristic of the HTLV-I (+) leukemic T cells in adult T-cell leukemia (ATL). Despite the expression of IL-2R bearing Tac antigen (IL-2R/p55), leukemic cells of the majority of ATL patients do not proliferate in response to IL-2. In the human NK cell line, YT, as well as in ATL-derived T cells, the co-expression of IL-2R/p55 and the second IL-2R without the Tac epitope (IL-2R/p70) is required to produce high-affinity IL-2R. To study the effect of HTLV-I on both of the IL-2Rs, we transfected a fragment of HTLV-I containing the p40X gene into YT cells. One of the 2 transfected YT clones (YT/pX-5.1) had an increased level of expression of IL-2R/p55. In contrast, expression of IL-2R/p70 was unaffected, as determined by Scatchard analysis and the cross-linking study using 125I-IL-2. Our results show that the T-cell phenotype is not required for induction of IL-2R/p55 by p40X. We suggest that HTLV-I infection induces a disproportionate induction of IL 2R/p55 without significant enhancement of IL-2R/p70 expression, resulting in the predominant expression of low-affinity IL-2R in ATL. IL-2R/p70 may be a critical parameter determining the IL-2 reactivity of HTLV-I-infected T cells as well as of normal lymphocytes. PMID- 2897344 TI - Repetitive monomorphic ventricular tachycardia aborted by sleep. AB - A 43-year-old woman with a 12-year history of palpitation was found to have recurrent monomorphic ventricular tachycardia resistant to beta-blockade but abolished by sleep. PMID- 2897345 TI - [Endodontic approach to injured teeth]. PMID- 2897346 TI - Multiple endocrine neoplasia type IIb--a case report. PMID- 2897347 TI - Molecular analysis of DQ beta 3.1 genes. AB - HLA class II genes have been implicated in susceptibility to a number of diseases. We have previously identified two allelic variants of DQw3 and have shown that DR4-DQ beta 3.2 haplotypes are associated with increased risk of IDDM whereas DR4-DQ beta 3.1 haplotypes are not. DR5 and DR8 DQw3+ individuals are exclusively DQ beta 3.1 and share numerous restriction sites within the DQ beta genes with DR4-DQ beta 3.1 individuals. In order to compare the DQ beta 3.1 genes associated with different haplotypes, we have sequenced coding and noncoding regions of the DQ beta genes from a DR4-DQ beta 3.1 HTC (ER) and a DR8-DQ beta 3.1 HTC (LUY). LUY and ER DQ beta genes share nucleotide substitutions in both the beta 1 and beta 2 exons, yielding six amino acid replacements distinguishing them from DQ beta 3.2. In the noncoding regions as well, LUY and ER share nucleotide substitutions distinguishing their DQ beta 3.1 genes from DQ beta 3.2. These data support the concept that the DQ beta 3.1 allele was introduced onto different backgrounds via homologous recombination. PMID- 2897348 TI - HLA-DP typing by analysis of DNA restriction fragment length polymorphisms in the HLA-DP beta subregion. AB - HLA class II antigens are encoded in the HLA-D region and are highly polymorphic. Southern hybridization technique was used to analyze restriction fragment length polymorphisms (RFLPs) in the DP beta gene and an attempt was made to correlate these with DP haplotypes derived from primed lymphocyte typing (PLT) analysis. Digestion of DNA from 32 Epstein-Barr virus (EBV)-transformed cell lines (of haplotypes DPw2, DPw3, DPw4, DPw5, and Cp63) with three different restriction endonucleases. Southern transfer, and hybridization to the DP beta cDNA probe revealed multiple fragments in all cell lines tested. The polymorphic patterns of these fragments were found to correlate with DP haplotypes, suggesting the possibility that the analysis of DNA RFLPs (DNA typing) in the HLA-DP beta subregion can distinguish and identify HLA-DP haplotypes. PMID- 2897349 TI - [Scholarship report from the 2d International Conference on Primary Health Care in London. "Health for all by the year 2000"]. PMID- 2897350 TI - Comments on tardive dyskinesia. PMID- 2897351 TI - Use of ultrasonography to diagnose Sertoli cell neoplasia and cryptorchidism in a dog. AB - Unilateral cryptorchidism and Sertoli cell tumor in the descended testis were provisionally diagnosed by use of ultrasonography in a 7-year-old Keeshond. The left testis was thought to have degenerated, but ultrasonography of the scrotum did not reveal evidence of testicular or epididymal tissue. The contralateral testis contained a hypoechoic mass believed to be a testicular tumor. Surgery and histopathologic findings confirmed the diagnosis. Ultrasonography of the scrotum and its contents should be considered for use in animals with suspected testicular neoplasia and/or degeneration. PMID- 2897353 TI - Differential response to the beta-adrenergic agonist cimaterol in mice selected for rapid gain and unselected controls. AB - Male mice selected for rapid 3 to 6 wk postweaning gain (M16) and unselected controls (ICR) were ad libitum fed a stock diet containing 0, 50 or 200 ppm cimaterol, a beta-agonist, from 4 to 7 or 4 to 10 wk of age. Mortality rate was higher in M16 than in ICR mice fed cimaterol (12.5 vs 1.3%; P less than .01). No mortalities occurred in either line fed the control diet. Line M16 exceeded (P less than .01) ICR in growth rate, feed intake, feed efficiency and lean index. Line X cimaterol level interactions (P less than .01) were found for the first three of these traits, although cimaterol level did not change line ranking. Epididymal fat as a percentage of empty body weight decreased at a faster rate in M16 than in ICR as cimaterol level increased. At 0 and 50 ppm, M16 exceeded ICR (P less than .05), but at 200 ppm there was no line difference (P greater than .05). Line M16 exceeded (P less than .05) ICR in blood glucose (5%), nonesterified fatty acids (4%) and lactate at 7 wk (9%), but lactate was higher in ICR at 10 wk (13%). Lines were not different in blood urea-N. Compared to zero cimaterol level, at 50 and 220 ppm glucose decreased (14% and 23%; P less than .05), nonesterified fatty acids decreased (3% and 29%; P less than .05), lactate increased (9% and 11%; P less than .05) and blood urea-N increased (3% and 16%; P less than .05). There were no line X cimaterol level interactions for blood metabolites. Differences in mortality rate, growth, feed consumption, feed efficiency and epididymal fat pad percentage between the high-growth and control lines in response to cimaterol may reflect genetic differences in mechanisms of metabolic regulation. PMID- 2897352 TI - Adult T cell leukemia-like disease experimentally induced in rabbits. AB - An HTLV-I-transformed T cell line, obtained from the peripheral blood of a virus infected (B/J X Chbb:HM) F1 rabbit, was able to kill syngeneic newborn rabbits within 7 days, when inoculated intraperitoneally at a dose of 1 X 10(8) cells. Inoculation of 1 X 10(7) cells killed or rendered moribund 50% of inoculated animals, while surviving animals exhibited cell-mediated cytotoxic activities against the transformed cells. The peripheral blood leukocyte counts increased in all surviving animals, in association with appearance of abnormal lymphocytes with convoluted or lobulated nuclei. Pathological examination of animals that died one week post-inoculation revealed no tumors in the abdominal cavity, but accumulation of ascites containing abnormal lymphocytes. Histological examination showed leukemic infiltration in the liver, lungs, spleen and mesenteric lymph nodes. The same cell line was also able to kill syngeneic adult rabbits in 8-10 days when inoculated intravenously, but not intraperitoneally, at a dose of 1 X 10(8) cells. Leukemic infiltration was observed in the major organs of these animals. Adult animals which were already virus carriers were resistant to this lethal inoculation. This rabbit ATL-like disease may prove to be useful as an experimental model for acute adult T cell leukemia. PMID- 2897355 TI - Effects of almitrine on respiration in unanesthetized newborn rabbits. AB - We previously demonstrated that almitrine, a peripheral chemoreceptor stimulant, increased tidal volume (VT), expired minute ventilation (VE), and respiratory frequency (f) and decreased inspiratory (TI) and expiratory time (TE) in sleeping adult cats. We now hypothesized that almitrine would induce an increase in ventilation in a young animal model. Respiration was studied by the barometric method in 11 unanesthetized New Zealand White rabbit pups between 3 and 6 days of age. Recordings were made in 0.21 FIO2 at base line and after cumulative intraperitoneal infusions of almitrine (2.5, 5.0, and 7.5 mg/kg). The chamber pressure deflection (proportional to VT after appropriate calculation) was computer sampled at 200 Hz. At least 100 breaths for each dose in each animal were analyzed. We found that a 7.5-mg/kg intraperitoneal dose of almitrine increased f to 135 +/- 9% (SE) of base line and decreased TE and TI to 72 +/- 8% and 79 +/- 8% of base line, respectively. Changes in VE, VT/TI, and VT were not significant. Recognizing that apnea is associated with inadequate ventilation and a prolonged TE (failure of the "inspiratory on-switch"), these results, particularly the increase in f and decrease in TE, suggest that almitrine might be useful in treating apnea in preterm infants. PMID- 2897354 TI - Effect of acute oral doses of T-2 toxin on tissue concentrations of biogenic amines in the rat. AB - T-2 toxin [3 alpha-hydroxy-4 beta, 15-diacetoxy-8 alpha-(3-methylbutyryloxy) 12,13-epoxytrichotec-9-ene] is an emetic Fusarium trichothecene mycotoxin known to cause lethargy, ataxia and feed refusal in economically important animals. Experiments were conducted to determine the effect of acute oral doses of T-2 toxin on tissue concentrations of neurotransmitters thought to play some role in regulation of feed consumption. Sixty-seven male weanling rats were intubated with a few grams of diet in a liquid slurry with or without 2.0 mg T-2 toxin per kilogram of body weight. At 1, 2, 4, 6, 8, 12, 24 and 48 h following dosing, rats were killed, and brains, spleens, hearts and adrenal glands were excised and analyzed for concentrations of neurotransmitters and metabolites using high performance liquid chromatography with electrochemical detection. Administration of T-2 toxin caused increases in brain concentrations of tryptophan and serotonin at the early time intervals after dosing. Brain concentrations of dopamine increased, whereas concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) decreased at the later time interals following dosing. Concentrations of dopamine were increased in adrenal glands, whereas epinephrine concentrations decreased. Epinephrine was detected in spleen and heart after administration of T-2 toxin. It was concluded that the increase in brain indoleamines induced by T-2 toxin could contribute to feed refusal in animals suffering from T-2 toxicosis. PMID- 2897356 TI - Cloning and nucleotide sequence of the aroA gene of Bordetella pertussis. AB - The aroA locus of Bordetella pertussis, encoding 5-enolpyruvylshikimate 3 phosphate synthase, has been cloned into Escherichia coli by using a cosmid vector. The gene is expressed in E. coli and complemented an E. coli aroA mutant. The nucleotide sequence of the B. pertussis aroA gene was determined and contains an open reading frame encoding 442 amino acids, with a calculated molecular weight for 5-enolpyruvylshikimate 3-phosphate synthase of 46,688. The amino acid sequence derived from the nucleotide sequence shows homology with the published amino acid sequences of aroA gene products of other microorganisms. PMID- 2897357 TI - Psychopharmacological treatment of elderly demented patients. AB - Elderly demented patients often suffer from accompanying psychiatric symptoms, including disturbances of mood and behavior, that may respond to psychotropic drug treatment. Despite the wide use of several medication groups--including antipsychotics, antidepressants, and sedative-hypnotics--data from double-blind clinical trials are limited. Some relevant controlled studies are reviewed, and guidelines for treatment based on the available data and clinical experience are described. Elderly demented patients can be treated psychopharmacologically. The choice of medication depends partly on its side effects. Initial dosages for the elderly should be lower than for younger adults. PMID- 2897358 TI - On the active site of liver acetyl-CoA. Arylamine N-acetyltransferase from rapid acetylator rabbits (III/J). AB - A covalent, catalytic intermediate of cytosolic liver acetyl coenzyme A: arylamine N-acetyltransferase (EC 2.3.1.5) from rapid acetylator rabbits (III/J) was isolated and chemically characterized. The active site was further studied using two covalent inhibitors, [2-3H]iodoacetic acid and bromoacetanilide. Inhibition experiments with [2-3H]iodoacetic acid at pH 6.9 showed that the incorporation of 0.7 mol of [2-3H]iodoacetic acid/mol of N-acetyltransferase led to rapid, irreversible loss of enzyme activity. Preincubation of the enzyme with acetyl coenzyme A (acetyl-CoA) completely protected against inactivation by [2 3H]iodoacetic acid. After incubating the N-acetyltransferase with [2-3H]acetyl CoA in the absence of an acceptor amine, an acetyl-cysteinyl-enzyme intermediate was isolated and characterized. Preincubation of N-acetyltransferase with iodoacetic acid prevented the incorporation of the [2-3H]acetyl group into the enzyme. The product analog, bromoacetanilide, caused a rapid irreversible loss of N-acetyltransferase activity. The reaction was pseudo first-order and saturated at high bromoacetanilide concentrations (KI = 0.67 mM; k3 = 1 min-1). Preincubation of the enzyme with acetyl-CoA prevented inactivation by the inhibitor. The acceptor amine 4-ethylaniline did not prevent inhibition. Incorporation of the inhibitor was directly proportional to the loss of activity showing a 1:1 stoichiometry of enzyme to inhibitor. The target amino acid was identified as cysteine by amino acid analysis of inhibitor-treated enzyme. PMID- 2897359 TI - Arylamine N-acetyltransferase from chicken liver. I. Monoclonal antibodies, immunoaffinity purification, and amino acid sequences. AB - Five monoclonal antibodies against arylamine acetyltransferase (EC 2.3.1.5) from the chicken liver were established by immunizing a mouse with a partially purified enzyme preparation. None of the antibodies cross-reacted with arylamine N-acetyltransferase from the livers of cow, rabbit, and rat, nor with arylalkylamine N-acetyltransferase from the chicken pineal gland, indicating a high specificity of the antibodies. By using the antibodies, two immunoaffinity purification procedures were elaborated: A partially purified enzyme preparation was incubated with the monoclonal antibody, and the resulting enzyme-IgG complex was separated by a protein A-Sepharose column. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed a single protein band with a molecular mass of 34 kDa in addition to the heavy and light chains of IgG. Secondly, an immunoaffinity column was prepared by immobilizing a monoclonal antibody to Sepharose 4B. After a partially purified enzyme preparation was absorbed on the column, N-acetyltransferase activity was eluted with 1 M NaCl and 1 M urea. The eluted sample contained a single 34-kDa protein. The purified enzyme preferred arylamines to arylalkylamines as substrates, indicating that it was arylamine N-acetyltransferase. The purified protein was subjected to digestion by lysylendopeptidase and separated by high performance liquid chromatography. Partial amino acid sequences of three peptides were determined by a gas-phase sequence analyzer. PMID- 2897360 TI - Arylamine N-acetyltransferase from chicken liver II. Cloning of cDNA and expression in Chinese hamster ovary cells. AB - A cDNA clone encoding the full coding region of chicken liver arylamine acetyltransferase (EC 2.3.1.5) was isolated from lambda gt10 cDNA library by screening with the 32P-labeled oligonucleotide deduced from the amino acid sequence reported in the preceding paper. The complete nucleotide sequence of the cDNA was determined, from which the amino acid sequence of N-acetyltransferase was deduced. It consisted of 1,302 nucleotides including a 861-nucleotide region coding for 287 amino acids with a molecular weight of 32,914. Two methods were applied to confirm that the cDNA encoded arylamine N-acetyltransferase. First, mRNA was synthesized in vitro by Bluescript and subsequently translated in vitro. The molecular mass of the translation product was 34 kDa consistent with that of the enzyme purified from the chicken liver. The translated protein was immunoprecipitated by a monoclonal antibody to N-acetyltransferase. Second, the cDNA was inserted into an expression vector pcDL1 and introduced into Chinese hamster ovary cells. The supernatant of the homogenate of transfected cells showed a high level of N-acetyltransferase activity with a substrate specificity comparable to that of the liver enzyme. Northern blot analysis revealed three mRNAs corresponding to 4.7, 2.0, and 1.4 kilobases. The levels of N acetyltransferase mRNAs were relatively high in the liver and distributed in various tissues. Genomic Southern blot analysis indicated the presence of only one gene in the chicken haploid genome. PMID- 2897361 TI - Steroid regulation of somatostatin mRNA in the rat hypothalamus. AB - The participation of gonadal steroid hormones in the regulation of the expression of the somatostatin gene in the hypothalamus and cerebral cortex was studied by using a quantitative densitometric hybridization assay which allows the direct measurement of specific somatostatin mRNA levels. The levels of somatostatin mRNA in hypothalamus were found to be significantly decreased following gonadectomy in both male and female rats (67% in males and 75% in females). Moreover, with in situ hybridization histochemistry somatostatin mRNA was similarly reduced following gonadectomy in the dorsal portion of the periventricular region and in the ventromedial nucleus. Estradiol dibenzoate treatment reversed the decrease in somatostatin mRNA in females within 24 h and testosterone treatment reversed the decrease in castrated males. In contrast, there was no significant change in cerebral cortex somatostatin mRNA levels after gonadectomy. These results suggest that sex steroids are involved in the regulation of the somatostatin gene in the hypothalamus, possibly at the transcriptional level. PMID- 2897362 TI - X-ray diffraction and time-resolved fluorescence analyses of Aequorea green fluorescent protein crystals. AB - The energy transfer protein, green fluorescent protein, from the hydromedusan jellyfish Aequorea victoria has been crystallized in two morphologies suitable for x-ray diffraction analysis. Hexagonal plates have been obtained in the P6122 or P6522 space group with a = b = 77.5, c = 370 A, and no more than three molecules per asymmetric unit. Monoclinic parallel-epipeds have been obtained in the C2 space group with a = 93.3, b = 66.5, c = 45.5 A, beta = 108 degrees, and one molecule per asymmetric unit. The monoclinic form is better suited for use in a structure determination, and a data set was collected from the native crystal. Time-resolved fluorescence measurements of large single crystals are possible due to the unique, covalently bound chromophore present in this molecule. Fluorescence emission spectra of Aequorea green fluorescent protein in solution and from either the hexagonal or monoclinic single crystal show similar profiles suggesting that the conformations of protein in solution and in the crystal are similar. Multifrequency phase fluorimetric data obtained from a single crystal were best fit by a single fluorescence lifetime very close to that exhibited by the protein in solution. The complementary structural data obtained from fluorescence spectroscopy and x-ray diffraction crystallography will aid in the elucidation of this novel protein's structure-function relationship. PMID- 2897363 TI - Arginine for glycine substitution in the triple-helical domain of the products of one alpha 2(I) collagen allele (COL1A2) produces the osteogenesis imperfecta type IV phenotype. AB - Skin fibroblasts from two affected members of a family with an autosomal dominant form of mild-moderate osteogenesis imperfecta produced two populations of type I collagen molecules. One population was normal and the other population contained alpha 2(I) chains which had a basic charge shift localized to a peptide from the carboxyl-terminal end of the triple-helical domain. The alpha chains in the abnormal molecules had increased post-translational modification along the entire triple-helical domain but the thermal stability was normal. We isolated a 28-kb BamHI fragment from the normal and mutant COL1A2 alleles from an affected family member. DNA sequence determination demonstrated that a single nucleotide change resulted in an arginine for glycine substitution at triple-helical position 1012, the last triple-helical glycine. These data demonstrate the stringent requirement for maintenance of the Gly-X-Y triplet sequence in type I collagen and suggest that point mutations which disrupt Gly-X-Y in alpha 2(I) produce milder clinical effects than similar mutations in alpha 1(I). PMID- 2897364 TI - Postnatal development of rat liver mitochondrial functions. The roles of protein synthesis and of adenine nucleotides. AB - It has been proposed that the acquisition of efficient energy-transducing mitochondria after birth is mediated by an ATP-dependent mechanism "that causes the rapid maturation of mitochondria without requiring either transcription or translation" (Pollak, J. K., and Sutton, R. (1980) Trends Biochem. Sci. 5, 23 27). Investigation of developmental changes in rat liver mitochondria during the first 6 postnatal h showed that fetal mitochondria had low State 4, State 3, and uncoupled rates of respiration, inefficient coupling between respiration and phosphorylation, and low membrane potentials and proton electrochemical gradients under State 4 conditions. In contrast, hepatic mitochondria from 1-h-old neonates showed increased respiratory control and ADP/O ratios and adult proton electrochemical gradient and membrane potential values. In parallel with these changes, mitochondria became enriched in adenine nucleotides and underwent a 50% reduction in matrix volume. During the first postnatal hour, an increase in mitochondrial succinic dehydrogenase, cytochrome c oxidase, and F1-ATPase activities takes place in the neonatal liver concurrent with a preferential postnatal increase in the in vivo rates of protein synthesis for mitochondrial proteins. In particular, the amount of F1-ATPase increased from 109 +/- 9 to 206 +/- 5 ng/microgram of mitochondrial protein in the first hour of postnatal life. Inhibitors of cytosolic protein synthesis present during the first 2 h of life blocked the postnatal increase in respiratory control and ADP/O ratios, succinic dehydrogenase activity, and F1-ATPase content; but they had no effect on the increase in adenine nucleotide concentrations and mitochondrial volume contraction. This indicates that the acquisition of an efficient coupling between respiration and phosphorylation is dependent on de novo protein synthesis and cannot be brought about by the postnatal increase in adenine nucleotides. The increase of State 4 and uncoupled rates of respiration during the first 2 postnatal h was resistant to protein synthesis inhibitors. We suggest that the postnatal increase in these parameters is due to the reduction of mitochondrial volume occurring during that time, which, in turn, may be triggered by the concurrent enrichment in adenine nucleotides. PMID- 2897365 TI - An autocrine factor from Reuber hepatoma cells that stimulates DNA synthesis and acetyl-CoA carboxylase. Characterization of biologic activity and evidence for a glycan structure. AB - Conditioned medium from Reuber H-35 or Fao hepatoma cells contains autocrine factors that both stimulate DNA synthesis and activate acetyl-coenzyme A (CoA) carboxylase in serum-deprived Fao cells. The factor(s), which appears within 4 h of serum-free culture, also increases the cell number and the mitotic index. The effects of the conditioned medium are insulinomimetic, both with respect to stimulation of DNA synthesis and acetyl-CoA carboxylase activity. However, no induction of tyrosine aminotransferase activity or stimulation of aminoisobutyric acid uptake is seen in response to the conditioned medium. Insulin over a 4-h period does not increase the concentration of DNA synthesis stimulating activity that is observed in the medium. This activity is dialyzable and is resistant to acid treatment or to heating to 60-100 degrees C and to trypsin digestion; it is not extracted with chloroform/methanol nor adsorbed by charcoal or by a C18 reverse-phase column. Fractionation of the conditioned medium derived from Reuber H-35 hepatoma cells by gel filtration chromatography reveals two low molecular weight (less than 1000) compounds that both stimulate DNA synthesis in Fao hepatoma cells. The larger compound (peak I) also stimulates the activity of acetyl-CoA carboxylase. The stimulatory effects of the peak I compound are destroyed by nitrous acid deamination, periodate oxidation, and methanolysis. Biosynthetic labeling studies indicate the probable presence of glucosamine, galactose, and perhaps phosphate in the peak I-activating material. No significant incorporation of either myoinositol or mannose into the active material has been observed. These data, taken together, are consistent with a glycan structure for this autocrine factor, which bears strong resemblance to similar insulinomimetic factors generated in BC3H1 myocytes and H-35 hepatoma cells in response to insulin and on digestion of membranes with a phosphatidylinositol-specific phospholipase C. Further characterization of this factor may provide insight into different pathways of insulin action and could provide a strategy to check autocrine-stimulated tumor growth. PMID- 2897366 TI - Characterization of a chloroplast sequence-specific DNA binding factor. AB - The large subunit of ribulose 1,5-bisphosphate carboxylase (rbcL) and the beta subunit of chloroplast ATP synthase (atpB) are encoded by divergently transcribed genes on the plastid genome. We have identified DNA binding factors specific for sequences located in the intergenic region between these two genes. Soluble plastid extracts from pea or whole cell extracts from maize protected a maize chloroplast DNA probe containing the 160-base pair region between the 5' ends of rbcL and atpB genes from exonuclease III digestion between positions -16 and -101 relative to the rbcL gene transcription start site. Competition assay with partial sequences from this intergenic region demonstrated that specific sequence(s) are required for the protection. The borders of the binding domain are conserved among the homologous regions of maize, tobacco, spinach, and pea chloroplast genomes. Gel filtration chromatography revealed a molecular weight of about 115,000 for the active complex involved in DNA binding. Using the exonuclease III protection assay, we have also shown that purified Escherichia coli RNA polymerase protects from +25 to -20 of the rbcL gene and from +21 to -23 of the atpB gene relative to their respective transcription start sites. These regions are analogous to open complexes found when E. coli RNA polymerase interacts with the prokaryotic promoters and are consistent with the ability of E. coli RNA polymerase to initiate transcription correctly on linear templates containing these chloroplast promoters. Possible role(s) for the chloroplast DNA binding factor in chloroplast gene expression and its regulation are discussed. PMID- 2897367 TI - The high molecular weight receptor to transforming growth factor-beta contains glycosaminoglycan chains. AB - Proteoglycans are constituents of the cell surface that may play important roles in the regulation of cell behavior. Here we report that the 250-kDa receptor subunit that binds the multifunctional protein, transforming growth factor-beta 1 (TGF-beta 1), contains chains of heparan sulfate and chondroitin sulfate and thus is a proteoglycan. Digestion of TGF-beta 1-receptor complexes with glycosaminoglycan (GAG)-specific degradative enzymes yield core proteins of 115 140 kDa. Cell monolayers that had been predigested with GAG-specific degradative enzymes were capable of binding high levels of TGF-beta 1, but the size of the binding components was shifted from the high molecular weight species to the lower molecular weight core proteins, indicating that GAG chains are not necessary for TGF-beta 1 binding to the cell. The presence of GAG chains on the receptor subunit indicates that it has the potential for interaction with the extracellular matrix. PMID- 2897368 TI - Fibronectin is a component of the sodium dodecyl sulfate-insoluble transglutaminase substrate. AB - Liver plasma membranes contain a morphologically distinct protein complex which serves as a substrate for the plasma membrane-associated transglutaminase. The complex, which appears as a two-dimensional sheet, is insoluble in sodium dodecyl sulfate and reducing agents and has been named SITS for sodium dodecyl sulfate insoluble transglutaminase substrate (Tyrrell, D. J., Sale, W. S., and Slife, C. W. (1988) J. Biol. Chem. 263, 1946-1951). Polyclonal antibodies raised against SITS were used to probe for soluble constituents of the matrix. Immunoblots showed that proteins of 230, 35, and 32 kDa reacted with the anti-SITS antiserum when the soluble fraction from a liver homogenate was examined. The 230-kDa protein was identified as fibronectin after observing cross-reactivity of anti SITS antiserum with authentic fibronectin and cross-reactivity of anti fibronectin antiserum with the 230-kDa cytosolic protein and purified SITS. Preincubating anti-SITS antiserum with purified fibronectin decreased immunostaining of the 230-kDa cytosolic protein and authentic fibronectin. Immunoblots of the plasma membrane fraction using anti-SITS and anti-fibronectin antisera showed that both antisera reacted with proteins at the top of the stacking gel (SITS) and of 230 kDa. In addition, the anti-SITS antiserum reacted with proteins of 85, 35, and 32 kDa. Immunofluorescence microscopy revealed that the anti-SITS and anti-fibronectin antisera both react with isolated SITS and with the same filamentous structures associated with intact plasma membranes. These studies show that fibronectin is a component of the plasma membrane matrix, SITS. This finding is consistent with the proposed role of this matrix which is to mediate cell-cell adhesion between hepatocytes in the tissue. PMID- 2897369 TI - Purification and properties of a vanadate- and N-ethylmaleimide-sensitive ATPase from chromaffin granule membranes. AB - A vanadate- and N-ethylmaleimide-sensitive ATPase was purified about 500-fold from chromaffin granule membranes. The purified preparation contained a single major polypeptide with an apparent molecular mass of about 115 kDa, which was copurified with the ATPase activity. Immunological studies revealed that this polypeptide has no relation to subunit I (115 kDa) of the H+-ATPase from chromaffin granules. The ATPase activity of the enzyme is inhibited about 50% by 100 microM N-ethylmaleimide or 5 microM vanadate. The enzyme is not sensitive to dicyclohexylcarbodiimide, ouabain, SCH28080, and omeprazole, which distinguishes it from Na+/K+-ATPase and the gastric K+/H+-ATPase. ATP and 2-deoxy ATP are equally effective substrates for the enzyme. However, the enzyme exhibited only 10% activity with GTP as a substrate. UV illumination of the purified enzyme in the presence of [alpha-32P]ATP exclusively labeled the 115 kDa protein. This labeling was increased by Mg2+ and strongly inhibited by Ca2+ ions. Similarly, the ATPase activity was dependent on Mg2+ and inhibited by the presence of Ca2+ ions. The ATPase activity of the enzyme was largely insensitive to monovalent anions and cations, except for F-, which inhibited the vanadate-sensitive ATPase. Incubation of the enzyme in the presence of [14C]N-ethylmaleimide labeled the 115 kDa polypeptide, and this labeling could be prevented by the addition of ATP during the incubation. A reciprocal experiment showed that preincubation with N ethylmaleimide inhibited the labeling of the 115-kDa polypeptide by [alpha 32P]ATP by UV illumination. This suggests a close proximity between the ATP binding site and an essential sulfhydryl group. A possible connection between the isolated ATPase and organelle movement is discussed. PMID- 2897370 TI - The purification and characterization of an acellular pertussis vaccine. AB - An acellular pertussis vaccine manufactured by Biken was investigated for purity, potency and toxicity. The vaccine was composed of almost equal proportions of pertussis toxin (PT) and filamentous hemagglutinin (FHA). The purity of the vaccine was 97-99%. The protective effects of component vaccines containing various ratios of PT and FHA were tested and it was found that the ratio of 1:1 provided the most effective vaccine. PMID- 2897371 TI - Bone cement and the liver. A dose-related effect? AB - The serum liver enzyme levels of 40 consecutive patients before and after cemented hip replacement were compared with a control group having operation without use of cement. Serum gammaglutamyl transferase (SGGT) was abnormally raised, for more than four days, in 12 of the 40 patients (32%) in whom bone cement was used, compared with one of the 36 control patients. The changes in SGGT levels after operation correlated with the weight of cement used (r = 0.66, p less than 0.001), but there was return to normal levels in all patients. A temporary dose-related effect of bone cement on liver function is demonstrated. PMID- 2897373 TI - Pediatric pain management. PMID- 2897372 TI - Interaction between pathogenic amebas and fibronectin: substrate degradation and changes in cytoskeleton organization. AB - Invasion of human tissues by the parasitic protozoan Entamoeba histolytica is a multistep process involving, as a first step, the recognition of surface molecules on target tissues by the amebas or trophozoites. This initial contact is followed by the release of proteolytic and other activities that lyse target cells and degrade the extracellular matrix. In other parasitic diseases, as well as in certain cancers, the interaction of invasive organisms or cells with fibronectin (FN) through specific receptors has been shown to be the initial step in target cell recognition. Interaction with FN triggers the release of proteolytic activities necessary for the effector cell migration and invasion. Here, we describe the specific interaction of Entamoeba histolytica trophozoites with FN, and identify a 37-kD membrane peptide as the putative receptor for FN. The interaction between the parasite and FN leads to a response reaction that includes the secretion of proteases that degrade the bound FN and the rearrangement of amebic actin into "adhesion plates" at sites of contact with FN coated surfaces. The kinetics of the interaction was determined by measuring the binding of soluble 125I-FN to the trophozoites and visualization of the bound protein using specific antibodies. Degradation of FN was measured by gel electrophoresis and the release of radioactivity into the incubation medium. Focal degradation of FN was visualized as black spots under the trophozoites at contact sites with fluorescent FN. We conclude that the interaction of E. histolytica with FN occurs through a specific surface receptor. The interaction promotes amebic cytoskeleton changes and release of proteases from the parasite. The binding and degradation of extracellular matrix components may facilitate the migration and penetration of amebas into tissues, causing the lesions seen in human hosts. PMID- 2897375 TI - Analysis of esmolol in human blood by high-performance liquid chromatography and its application to pharmacokinetic studies. PMID- 2897374 TI - Drugs, learning and cognitive function in children--an update. PMID- 2897376 TI - High-performance liquid chromatographic assay for dilevalol in human plasma and urine using a PRP-1 column and fluorimetric detection. AB - A single high-performance liquid chromatographic (HPLC) assay for the quantitative determination of dilevalol, the R,R isomer of labetalol, was developed for both plasma and urine. A significantly improved limit of detection for dilevalol in plasma was accomplished by extensive modification of an HPLC assay originally developed in our laboratory for labetalol. This simplified method is readily adaptable to urine and represents the first reported HPLC assay for the quantitative determination of dilevalol in this biofluid. Drug was recovered from plasma or urine by partition into diethyl ether under mildly alkaline conditions and back-extraction into dilute acid. Reversed-phase separation of dilevalol and the internal standard was accomplished on a 150 X 4.1 mm column commercially packed with a spherical (5 micron) macroporous copolymer (PRP-1). No interferences were observed in extracts obtained from drug-free plasma or urine. Selectivity for dilevalol in the presence of other beta-blockers was established. This method demonstrated a linear detector response to concentrations of unchanged drug typically observed in urine and plasma following once-a-day treatment with dilevalol hydrochloride (100-800 mg). The lowest limit of reliable quantitation was established at 1 ng/ml in plasma. The intra-assay precision (coefficient of variation) remained less than 6% at all concentrations evaluated from 1 to 800 ng/ml. In urine, the lowest limit of quantitation was validated to 20 ng/ml where the intra-assay precision (coefficient of variation) for unchanged drug was less than 4% at all concentrations evaluated up to 400 ng/ml. This method is suitable for routine quantitation of unchanged drug in human plasma and urine following the administration of therapeutically effective doses of dilevalol hydrochloride. PMID- 2897378 TI - Operative andrology. AB - Surgical corrections of male fertility disturbances are discussed. Following a short historical review, operative treatment of the undescended testicle, the indication and date of surgery and postoperative andrological results are dealt with. Modern principles of varicocoele surgery are discussed with special attention to fertility correction. Surgical treatment of vas deferens obstruction, results and microsurgical interventions concerning vaso-epididymal anastomoses and vasovasostomies are also described together with the ultimate possibilities for surgical therapy of sexual disturbances. PMID- 2897377 TI - Thin-layer chromatographic screening method for the tranquillizers azaperone, propiopromazine and carazolol in pig tissues. AB - A procedure is described for the detection of azaperone, propiopromazine and carazolol in pig muscle, liver and kidney tissue. The method comprises extraction from an alkaline tissue homogenate with diethyl ether, followed by cleaning up and concentration of the extract on a silica gel solid-phase extraction column. Two-dimensional thin-layer chromatography on a silica plate was used for the detection of the tranquillizers. Detection levels were 25 micrograms kg-1 for propiopromazine, 50 micrograms kg-1 for azaperone (or its metabolite azaperol) and 125 micrograms kg-1 for carazolol. In pigs treated with the usual doses the presence of propiopromazine and azaperol could be established in kidney tissue 8 h after administration, whilst in injection sites all three tranquillizers could be detected. PMID- 2897379 TI - View from the Nation's Capital. DEA considers relaxing restrictions on medical use of marijuana. PMID- 2897380 TI - A study of buspirone co-presented with antihistamines in 68 anxious ambulatory patients. PMID- 2897382 TI - Catecholamine neurons in the brainstem of the reptile Caiman crocodilus. AB - Immunohistochemical methods were used to map the distribution of neurons exhibiting tyrosine hydroxylase-like immunoreactivity (TH) in the brainstem of the reptile Caiman crocodilus. The results reveal that many catecholamine systems previously described in mammalian and avian species are present in the brainstem of the caiman. Within the medulla, many immunoreactive neurons surround the central canal. This neuronal field extends rostrally to the level of the dorsal motor nucleus of the vagus. Many TH neurons overlap the region of the solitary nucleus, and an extensive system of fibers derived from these neurons extends ventrally and laterally into the region immediately bordering the descending nucleus of the trigeminal nerve. Some TH neurons are also present in the ventrolateral tegmentum of the medulla at this level. A large number of TH cells are present in the pons and midbrain. These include the locus coeruleus, nucleus subcoeruleus ventralis, nucleus subcoeruleus dorsalis, substantia nigra (Brauth et al., '83), and area ventralis of Tsai. The subcoeruleus nuclei are considerably larger in the caiman than in other reptilian species including turtles and lizards and closely resemble the subcoeruleus nuclei of birds in terms of position and anterior-posterior extent. Within the diencephalon, numerous small, intensely staining, TH-immunoreactive and CSF-contacting neurons were observed within the preoptic recess and in close proximity to the ventricular wall at rostral hypothalamic and preoptic levels. Many intensely stained, immunoreactive cell bodies were observed in the medial hypothalamus similar in position to the A13 cell group of mammals. In the subthalamus, TH neurons completely surround the ventral peduncle of the forebrain bundle (which contains fibers of the ansa lenticularis) and extend into the ventromedial and ventrolateral thalamic areas. A rich plexus of TH-positive axons and terminals invests the external layer of the median eminence. PMID- 2897381 TI - Immunohistochemical and in situ hybridization analysis of the development of the rat somatostatin-containing neocortical neuronal system. AB - The chemical differentiation of somatostatin (SS) neurons in rat neocortex was characterized by molecular biochemical and morphological methods. Northern (RNA) blotting indicates that regional distribution of SS mRNA correlates with the known distribution patterns of SS-containing neurons in the adult, while similar analysis of poly (A)+ RNA isolated from telencephalon at various times postnatally shows an increase between P9 and P15, with a slight decrease in the adult. In situ hybridization with a probe specific to SS mRNA, and immunohistochemistry using antisera specific for the N-terminally extended form of SS, SS28, and SS28(1-12), were used to detect neocortical neurons containing this mRNA or its translation product. The appearance of SS mRNA is coincident with detectable immunoreactivity for SS peptides. The expression of the SS gene by cortical neurons occurs in two waves. From P1 to P11, hybridizing neurons are predominant below the cortical plate in the developing infragranular layers. Immunohistochemical analysis of immunoreactivity to SS28 reveals a significant development of this neocortical system by late gestation (E20). At this point SS28(1-12), the predominant SS form detected, is mainly in neurons of the subplate, with less detectable immunoreactivity in the intermediate zone and cortical plate. By P2, neurons in the subplate exhibit detectable SS28 and SS28(1 12). Although immunoreactive perikarya are no longer detectable at P2 in the cortical plate or marginal zone, a very dense plexus of SS28(1-12) fibers is seen in the subplate, marginal zone, and intermediate zone; relatively few immunoreactive fibers are found in the cortical plate. By P12, a dramatic shift occurs; a large supragranular population of these SS neurons is observed by both mRNA and antibody methods, as is a subsequent decrease in number in the adult. The shift in immunoreactivity occurs with supragranular SS28-containing neurons now prominent, and SS28(1-12)-containing neurons and fibers greatly diminished. The number of neurons containing SS mRNA or SS28 immunoreactivity decreases from P12 to adult, when these neurons exhibit a bilaminar distribution. Neurons immunoreactive for SS28(1-12) are now sparsely distributed throughout the cortex, while SS28(1-12) fibers densely innervate layers I and V/VI. PMID- 2897383 TI - Supraspinal nocifensive responses of cats: spinal cord pathways, monoamines, and modulation. AB - These experiments were conducted to determine (1) whether dorsal and ventral ascending spinal pathways can each mediate unlearned supraspinal nocifensive responses of cats to noxious thermal stimuli and (2) whether interrupting the spinal projection of supraspinal monoaminergic neurons alters the excitability and natural modulation of these responses. In partially restrained cats, thermal pulses (greater than or equal to 47 degrees C) delivered to the hindlimbs of intact cats or rostral to lesions of the thoracic spinal cord elicited abrupt body movements and interruption of eating (or of exploring for) liquified food. These electronically monitored responses automatically terminated the stimulus. Natural modulation of responsiveness was produced by delivering food and thermal stimuli simultaneously; this reduced response probability by an average of 41%. Complete transection of the thoracic spinal cord eliminated both thermally elicited responses and orienting responses to noxious and tactile mechanical stimulation of the hindlimbs. Ventral bilateral thoracic spinal cord lesions that spared only the dorsal funiculus and portions of the dorsolateral funiculus (three cats) significantly reduced orienting responses to all mechanical hindlimb stimuli and reduced, but did not eliminate, movement and interrupt responses to noxious thermal hindlimb stimuli. Response latency was unaffected. Food-induced response suppression persisted although lumbar spinal cord concentrations of serotonin (5HT) and norepinephrine (NE) were markedly reduced. A bilateral lesion of the dorsal funiculi and dorsal portions of the dorsolateral funiculi (one cat) also reduced nocifensive responsiveness, but only the NE concentration in lumbar spinal cord was reduced significantly relative to a matched cervical sample. In contrast, deep bilateral lesions of the dorsolateral funiculi (two cats) produced an increase in the probability of movement and interrupt responses without affecting either response latency or food-induced response suppression. Lumbar spinal cord concentrations of NE and, in one cat, 5HT were reduced. We conclude that (1) the dorsal and ventral spinal funiculi are each sufficient to initiate and necessary to maintain normal supraspinally organized nocifensive behavior in the cat; (2) descending monoaminergic pathways are not necessary for the phasic modulation of these responses; and (3) the tonic excitability, but not the phasic modulation, of these responses is determined in part by fibers in the dorsolateral funiculus. PMID- 2897384 TI - Pemphigus foliaceus-like, immunologically negative dermatosis in a patient with T cell chronic lymphocytic leukemia. AB - A 56-year-old black man developed a pemphigus foliaceus-like bullous eruption as the initial presentation of chronic T cell lymphocytic leukemia. Histologic examination disclosed superficial acantholysis consistent with pemphigus foliaceus and an infiltrate of atypical lymphoid cells in the papillary dermis. Repeated direct and indirect immunofluorescence studies yielded negative results. Acantholysis could be reproduced in vitro by incubation of normal human skin with the patient's serum and plasma but not with blister fluid. In the following months, the course of the bullous eruption paralleled that of the leukemia. PMID- 2897385 TI - Effect of human growth hormone-releasing factor (1-29)NH2 on growth hormone release and milk production in dairy cows. AB - Twelve cows (209 d in lactation, 642 kg BW) were used in an experiment conducted over four 10-d periods (one preinjection, one injection, and two postinjection). Gelatine (n = 6) or 10 mg of growth hormone-releasing factor in gelatine (n = 6) was injected subcutaneously at 1000 h every day on d 11 to 20. Data were averaged for the last 5 d of each period. During the injection period, milk, fat, and protein yields increased by 3 kg.d-1 (14.3%), .14 kg.d-1 (16.7%), and .12 kg.d-1 (15.4%), respectively. Moreover, milk, fat, and protein yields for the treated cows remained higher than for the control cows until the last postinjection period. Growth hormone response was evaluated from blood samples withdrawn from 2 h prior to 8 h postinjection on d 11, 15, and 20 and on d 40. After growth hormone-releasing factor injection, peaks and area under the curve were 24.5, 30.8, and 47.0 ng.ml-1 and 2475, 3979, and 3741 ng.ml-1.min-1 on d 11, 15, and 20, respectively. On d 40, there was no difference in growth hormone concentrations in blood between control and treated cows. These results demonstrate that 10 d of daily injection of a growth hormone-releasing factor increases milk production by 14.3% (3 kg.d-1) and still induces growth hormone release at the end of the injection period without any sign of refractoriness. PMID- 2897386 TI - Treatment of severe social phobia: effects of guided exposure with and without cognitive restructuring. PMID- 2897387 TI - Endogenous opiate system and systematic desensitization. PMID- 2897388 TI - Comparison of the efficacy and safety of loratadine, terfenadine, and placebo in the treatment of seasonal allergic rhinitis. AB - The efficacy and safety of loratadine, 40 mg once daily, were compared with terfenadine, 60 mg twice daily, and placebo in controlling symptoms of ragweed hay fever. The study was a randomized, multicentric, parallel-group, double-blind design involving 280 patients divided into three groups receiving either loratadine, terfenadine, or placebo for a period of 14 days in the autumn of 1984. Both loratadine and terfenadine demonstrated a statistically greater reduction in symptom score compared to placebo. They were not statistically different from each other, and there was no statistical difference in the incidence of side effects between the two drugs. PMID- 2897389 TI - H1 receptor antagonist treatment of chronic rhinitis. AB - In patients with chronic rhinitis, H1 receptor antagonists play an important role in relieving the symptoms of sneezing, itching, and rhinorrhea. New information about the pharmacokinetics and pharmacodynamics of first-generation H1 receptor antagonists such as chlorpheniramine has become available in the past few years. Comprehensive pharmacokinetic and pharmacodynamic studies of new relatively nonsedating H1 receptor antagonists such as terfenadine, astemizole, loratadine, and cetirizine are appearing. An understanding of the differences in pharmacokinetics and pharmacodynamics among H1 receptor antagonists is required for optimal use of these drugs. PMID- 2897390 TI - Topical intranasal corticosteroid therapy in rhinitis. AB - This paper reviews the current clinical information on the newer corticosteroid aerosols used in the management of rhinitis: beclomethasone dipropionate, flunisolide, fluocortin butylester, budesonide, and triamcinolone acetonide. Discussed are their pharmacologic properties, including our most recent understanding of their possible mode of action, comparative efficacy to other agents, indications, side effects, and general educational principles regarding their use. PMID- 2897391 TI - Acute confusional states in elderly patients treated for femoral neck fracture. AB - The aims of this study were to estimate the incidence of acute confusional state (ACS), its predisposing factors and consequences in 111 consecutive patients operated for fractured neck of the femur. The incidence of ACS was 61 percent and the predicting factors were old age and dementia. Drugs with anticholinergic effect, depression, and previous stroke were factors that seemed to be associated with the development of ACS. Ninety-two percent of the patients who had severe perioperative blood pressure drops developed ACS. The consequences of ACS were prolonged ward-stay at the orthopedic department, a greater need for long-term care after discharge, and poor walking ability at discharge and six months after surgery. The confused patients also had more complications, such as urinary problems, feeding problems and decubital ulcers, as compared with the nonconfused patients. PMID- 2897392 TI - The effect of selective electrical stimulation of non-myelinated vagal fibres on heart rate in the rabbit. AB - The bradycardia evoked by electrical stimulation of the peripheral cut end of the rabbit vagus nerve is mediated by both myelinated and non-myelinated fibres. The purpose of this study was to assess the effects of non-myelinated fibres on heart rate in the rabbit using selective electrical stimulation techniques. In 8 rabbits selective activation of non-myelinated fibres using reversed polarity triangular shaped pulses (10 Hz, 20 s), resulted in a slowly developing fall in heart rate of 24.1 +/- 1.1 beats/min which outlasted the period of stimulation by 58.4 +/- 4.2 s. In 4 rabbits stimulation of myelinated fibres at 10 Hz for 20 s resulted in a fall in heart rate of 24.5 +/- 2.6 beats/min. On stimulation of both myelinated and non-myelinated fibres heart rate fell by 39.9 +/- 3.2 beats/min. Heart rate returned rapidly to control value following stimulation of myelinated fibres (5.6 +/- 0.5 s) but only slowly after stimulation of both myelinated and non-myelinated fibres (56.7 +/- 4.9 s). Atropine (5 mg/kg, i.v.) abolished all effects of vagal stimulation on heart rate. Hexamethonium (15 mg/kg, i.v.) abolished the effect of myelinated fibres on heart rate but did not affect the fall in heart rate produced by non-myelinated fibres. We suggest that the prolonged effects on stimulation of non-myelinated fibres may reflect the persistent action of a non-cholinergic excitatory transmitter at the cardiac parasympathetic ganglia. PMID- 2897393 TI - Antigen-presenting cells for Lyt-2+ cells. I. Stimulation of unprimed Lyt-2+ cells by H-2 different Thy-1-Ia- cells prepared from spleen and bone marrow. AB - In agreement with previous studies on Ia- tumor cells, evidence is presented that primary MLR of purified Lyt-2+ T cells to class I alloantigens can be elicited by a minor population of Thy 1- Ia- cells present in normal spleen, bone marrow, and day-13 fetal liver; these cells are non-stimulatory for L3T4+ T cells. The data strengthen the view that primary responses of Lyt-2+ cells do not require the presence of Ia+ cells. PMID- 2897394 TI - Identification of a murine pan-T cell antigen which is also expressed during the terminal phases of B cell differentiation. AB - A new rat anti-mouse mAb, designated S7, is described. The antibody, an IgG2a, reacts with all Thy-1.2-positive cells and all granulocytic cells in the marrow. Resting B cells are non-reactive but, during the terminal phases of LPS-induced B cell differentiation, the S7 determinant appears and reaches high levels of expression. S7 will probably be useful in studies aimed at subdividing the later stages of the B cell maturation process. PMID- 2897395 TI - Defective activation of T suppressor cell function in nonobese diabetic mice. Potential relation to cytokine deficiencies. AB - Nonobese diabetic (NOD) is an inbred mouse strain susceptible to development of T cell-mediated autoimmune diabetes. The strain is characterized by high percentages of T lymphocytes in lymphoid organs. The syngeneic mixed lymphocyte reaction (SMLR), a T cell response to self MHC class II Ag, is reportedly involved in the generation of a number of immunoregulatory cells, including suppressor inducers. A severely depressed SMLR characteristic of certain other autoimmune strains was found in NOD but not in nonautoimmune SWR/Bm mice. Moreover, IL-2 produced by NOD T cells at day 6 in an SMLR was at least one hundredfold reduced compared with SWR, and NOD T cells harvested from an SMLR at day 6 were functionally defective when tested for ability to induce suppression of an allogeneic MLR. However, functionally competent suppressor T cells were generated in NOD splenic leukocyte cultures in response to Con A, and IL-2 release from these was equivalent to that released by Con A-stimulated SWR splenocytes. A deficiency in cytokine release was not limited to IL-2, because peritoneal exudate cells from NOD exhibited a greatly diminished sensitivity to LPS-stimulated IL-1 release in comparison to SWR mice. IL-2 supplementation both in vitro and in vivo restored the ability of NOD T cells to respond in a SMLR, with production of cells capable of inducing suppression. Like SMLR-activated T cells from untreated SWR controls, SMLR blasts from IL-2-treated NOD mice were enriched for the L3T4 phenotype. IL-1 supplementation in vitro resulted in partial restoration of T suppressor activation in a SMLR. The depressed SMLR exhibited by NOD mice was apparently a stimulator cell dysfunction, because NOD stimulator cells failed to activate T cells from (SWR x NOD)F1 mice, whereas stimulators from SWR or F1 mice were capable of doing so. Collectively, these results suggest a defect in suppressor cell activation rather than an absence of this immunoregulatory cell population. PMID- 2897396 TI - Expression of proto-oncogenes in normal and tumor tissues of human skin. AB - The expression of c-fos, c-myc, Ha-ras, N-ras, EGF-receptor, and cardiac actin genes was examined in 7 normal epidermis, 3 cellular nevi, and 8 skin tumors including 6 malignant and 2 benign tumors of human origin. These genes were transcribed in most normal and tumor tissues, though no tumor-specific expression of proto-oncogenes (c-fos, c-myc, Ha-ras, and N-ras) could be detected. However, there was a characteristic parallelism between the expression of c-fos and c-myc in normal epidermis, while the parallelism was not always definite in skin tumors. The ratio of c-fos/c-myc transcripts in normal epidermis was constant compared with the expression of other genes examined. These data suggest that c fos and c-myc are expressed in all normal skin tissues, and that maintenance of a constant ratio of c-fos/c-myc is closely related to ordered cell growth of the tissues. PMID- 2897397 TI - Molecular evolution of pathogenic Escherichia coli. PMID- 2897398 TI - Penicillin resistance and defective lysis in clinical isolates of pneumococci: evidence for two kinds of antibiotic pressure operating in the clinical environment. AB - Seventy percent of clinical isolates of penicillin-resistant pneumococci also exhibit defective lysis when treated with penicillin exceeding the minimal inhibitory concentration (MIC). To provide a possible explanation for the frequent association of these two traits, we exposed penicillin-susceptible pneumococci to two kinds of antibiotic pressures in the laboratory. Treatment of cultures with cycles of high concentrations of penicillin (20 X MIC) followed by growth of the survivors in drug-free medium selected for lysis-defective mutants that died only slowly during antibiotic treatment but had unchanged MICs. Exposure to sustained, low levels of penicillin produced resistant mutants, with elevated MICs, that lysed normally with penicillin. We suggest that the cyclic antibiotic exposure generally used in the clinical setting may select primarily for enhanced survival. From these survivors a second type of antibiotic exposure- sustained antibiotic concentrations just above the MIC (concentrations that may be restricted to the tail-end trough of a dosing interval)--selects for penicillin-resistant mutants. PMID- 2897400 TI - Identification of the antigenic components of Hantaan virus reacting with rabbit antisera and sera from patients with hemorrhagic fever with renal syndrome. PMID- 2897399 TI - Intrathecal synthesis of antibodies to human T lymphotropic virus type I and the presence of IgG oligoclonal bands in the cerebrospinal fluid of patients with endemic tropical spastic paraparesis. AB - Tropical spastic paraparesis (TSP), a neuromyelopathy predominantly involving the pyramidal tract and commonly observed in tropical and equatorial areas, was recently found to be associated with human T lymphotropic virus type I (HTLV-I). We investigated sera and cerebrospinal fluid (CSF) from 19 patients with TSP who were from the Caribbean area, French Guiana, and Africa. Our results showed an elevated intra-blood-brain barrier IgG synthesis rate and an elevated IgG index, with an increased HTLV-I antibody-to-albumin ratio and the presence of CSF oligoclonal bands in the majority of the patients. These data, in association with similar HTLV-I antibody patterns between patients with TSP who were from these three regions, strengthen the probable etiologic role of HTLV-I in the pathogenesis of such chronic neuromyelopathies. PMID- 2897401 TI - The immune response in amoebiasis. PMID- 2897402 TI - Studies on blood sucking insects in Suez City Egypt. PMID- 2897403 TI - [An immunological study of human T-cell-leukemia virus type I (HTLV-I) infection (I)--Detection of low-titer anti-HTLV-I antibodies by HTLV-I associated membrane antigen (HTLV-MA) method]. PMID- 2897404 TI - [An immunological study of human T-cell leukemia virus type I (HTLV-I) infection (II)--Radioimmunoprecipitation and SDS-polyacrylamide gel electrophoretic analysis of antibody of carriers]. PMID- 2897406 TI - Contrasuppression. Symposium. PMID- 2897405 TI - The role of contrasuppressor T cells in the adoptive transfer of contact sensitivity responses to picryl chloride. PMID- 2897407 TI - The role of contrasuppression in tumor regression. PMID- 2897408 TI - Role of contrasuppressor T cells in the antibody response to type III pneumococcal polysaccharide. PMID- 2897409 TI - Phenotypic and functional characterization of human contrasuppressor cell interactions. PMID- 2897410 TI - Function and regulation of SRBC-induced contrasuppressor T cells which modulate suppression of MOPC-315 cell secretory differentiation in vivo and in vitro. PMID- 2897411 TI - Contrasuppression in autoimmunity. PMID- 2897414 TI - Effect of beta 2-stimulant on utero-umbilical blood flow in normal and growth retarded fetuses. PMID- 2897412 TI - Contrasuppression in the mucosal immune system. PMID- 2897415 TI - [Transmission of HTLV-I infection from mothers to children]. PMID- 2897416 TI - [Mother-to-child transmission of human T-lymphotropic virus type-I]. PMID- 2897413 TI - Induction of contrasuppression is restricted by genes mapping to the IgH locus. PMID- 2897417 TI - [Cryptococcal meningitis with human T-cell leukemia virus type I carrier: report of a case]. PMID- 2897419 TI - [Successful therapy of VIPoma with the long-acting somatostatin analogue SMS 201 995]. PMID- 2897418 TI - [10-year clinical course of a patient with chronic adult T-cell leukemia]. PMID- 2897420 TI - Evaluation of sudden death in psychiatric patients with special reference to phenothiazine therapy: forensic pathology. AB - The investigation of sudden unexpected death in psychiatric patients and the ensuing litigation has brought to our attention many unusual features important in the evaluation of such deaths. Certain pathophysiologic mechanisms of death, rarely encountered in routine forensic science practice, may be important in determining the cause of death in psychiatric patients, especially in cases where the autopsy is unrevealing. Of particular concern is a tendency in the current literature to implicate phenothiazines as a cause of death when the death investigation and the autopsies are incomplete. Thus, based on our experience and on a review of the current literature, we have set forth factors that the forensic pathologist should consider when faced with a sudden psychiatric death. A case report illustrates these unique aspects of scene investigation and analysis of terminal events and autopsy findings. PMID- 2897421 TI - 3,4-Methylenedioxymethamphetamine (MDMA) and other amphetamine derivatives. AB - As various substances of abuse come under Drug Enforcement Administration (DEA) Schedule restrictions, slightly modified derivatives (designer drugs) replace them. A series of amphetamine derivatives are discussed in this presentation. Applicable analytical methods are presented. Details of cases handled by the office (hospital patients, driving while under the influence/driving under the influence of drugs [DWI/DUID], and medical examiner cases) are discussed. PMID- 2897423 TI - Effect of local injection of cysteamine and cystamine on somatostatin and neuropeptide Y levels in the rat striatum. AB - Cysteamine and its dimeric form cystamine have been applied to the rat striatum by local injection. Both compounds resulted in a dose-dependent decrease of somatostatin levels. Maximal reduction of somatostatin (by about 50%) was obtained at a dose of 50 micrograms of cysteamine or cystamine after about 6 h. All three molecular weight forms of somatostatin--somatostatin-14, somatostatin 28, and the 13,000 molecular weight form of somatostatin--were reduced, as shown by size exclusion HPLC. Injection of radiolabeled cystamine revealed a fast conversion of the compound to cysteamine, suggesting it is active in the monomeric form. The levels of neuropeptide Y, which is colocalized with somatostatin in striatal neurons, failed to be changed by local or intraperitoneal injection of cysteamine, suggesting that this treatment does not affect vesicles of somatostatin/neuropeptide Y neurons. PMID- 2897422 TI - Regenerated fibers of the lamprey spinal cord can coordinate fictive swimming in the presence of curare. AB - Recently evidence was presented that, following transection, spinal cords of larval lampreys could regenerate functional connections. The demonstration in isolated spinal cord-notochord preparations consisted of fictive swimming coordinated across the lesion site. In the study reported here curare was added to the bath to eliminate the possible contribution from reflexes mediated by contractions from any remaining muscle fibers attached to the notochord. Coordination remained in the presence of curare, adding further evidence that indeed the regenerated fibers formed functionally appropriate connections. PMID- 2897424 TI - Transmitter-like release of endogenous 3,4-dihydroxyphenylalanine from rat striatal slices. AB - Biphasic electrical field stimulation (0.5-5 Hz, 2 ms, 25 V, 3 min) and high K+ (10-30 mM, 5 min) released endogenous 3,4-dihydroxyphenylalanine (DOPA) from superfused rat striatal slices. Characteristics of the DOPA release were compared with those of 3,4-dihydroxyphenylethylamine (dopamine, DA). Electrical stimulation at 2 Hz evoked DOPA and DA over similar time courses. alpha-Methyl-p tyrosine (0.2 mM) markedly reduced release of DOPA but not of DA. Maximal release (0.3 pmol) of DOPA was obtained at 2 Hz and at 15 mM K+. The impulse-evoked release of DOPA and DA was completely tetrodotoxin (0.3 microM) sensitive and Ca2+ dependent and the 15 mM K+-evoked release was also Ca2+ dependent. On L-[3,5 3H]tyrosine (1 microM) superfusion, high K+ (15 and 60 mM) released DOPA and DA together with concentration-dependent decreases in tyrosine 3-monooxygenase (EC 1.14.16.2) activity as indicated by [3H]H2O formation, followed by concentration dependent increases after DOPA and DA release ended. These findings suggest that striatal DOPA is released by a Ca2+-dependent excitation-secretion coupling process similar to that involved in transmitter release. PMID- 2897425 TI - Regional levels of neurotransmitter markers in the pigeon telencephalon: a comparison with possibly homologous areas of the rat telencephalon. AB - The levels of cholinergic, gamma-aminobutyric acidergic (GABAergic), and excitatory amino acid neurotransmitter markers have been measured in 18 regions of the pigeon telencephalon as well as in supposedly homologous areas of the rat telencephalon. Among the basal telencephalic areas, some similar patterns of regional distribution were observed, with the noticeable exception of the ratio of levels of cholinergic markers between the striatum and globus pallidus, which was much larger in the rat than in the pigeon. In the rat cortical areas, some interesting differences were noticed among the archicortex, the paleocortex, and various parts of the neocortex. In particular, the area identified as prefrontal cortex by previous studies was significantly richer in cholinergic and excitatory amino acid markers and poorer in GABAergic activity than other neocortical regions. In the pigeon, presumedly neocortical equivalent areas--in particular, those constituting the dorsal ventricular ridge--were quite variable in levels of cholinergic markers, and some apparently well-established areas homologous to mammalian neocortex showed exceptionally low levels of cholinergic markers. The higher variability in levels of neurotransmitter-related markers shown by cortically equivalent areas of the avian dorsal ventricular ridge, as compared with the more uniform pattern present in basal telencephalic regions, may be the result of a greater plasticity of these structures during evolution, in response to different selective pressures. PMID- 2897426 TI - Alterations in retinal tyrosine and dopamine levels in rats consuming protein or tyrosine-supplemented diets. AB - The ad libitum ingestion of casein diets varying in protein content altered serum and retinal levels of tyrosine. The serum tyrosine level rose when protein ingestion was increased from 6 to 24% casein. In rats consuming high-protein diets (40% casein), no further increase in serum tyrosine level occurred, although the levels of other large neutral amino acids, which compete with tyrosine for retinal uptake, continued to rise. The activity of the liver enzyme tyrosine aminotransferase varied directly with the percentage of protein in the diet and may partially explain the failure of chronic high-protein feeding to increase serum tyrosine levels. The retinal tyrosine concentration was significantly correlated with the serum tyrosine level and with the serum tyrosine ratio at all levels of protein intake. Retinal 3,4 dihydroxyphenylalanine synthesis and dopamine (DA) level varied in parallel with the level of the precursor, tyrosine. Addition of pure L-tyrosine (1, 2, or 4%) to normal protein diets resulted in a stepwise increase in serum and retinal tyrosine levels and retinal DA turnover. Alterations of retinal tyrosine level as a result of change in amount of dietary protein or by its addition to the normal diet can influence retinal DA synthesis and release. PMID- 2897427 TI - Characterization of the inhibitory action of botulinum neurotoxin type A on the release of several transmitters from rat cerebrocortical synaptosomes. AB - Under optimised conditions for intoxication, botulinum neurotoxin type A was shown to inhibit approximately 90% of Ca2+-dependent K+-evoked release of [3H]acetylcholine, [3H]noradrenaline, and [3H]dopamine from rat cerebrocortical synaptosomes; cholinergic terminals were most susceptible. In each case, the dose response curve for the neurotoxin was extended, with about 50% of evoked release being inhibited at approximately 10 nM whereas 200 nM was required for the maximal blockade. This may suggest some heterogeneity in the release process. The action of the toxin was time and temperature dependent and appeared to involve binding and sequestration steps prior to blockade of release. The neurotoxin failed to exert any effect on synaptosomal integrity or on Ca2+-independent release of the transmitters tested; it produced only minimal changes in neurotransmitter uptake although small secondary effects were detected with cholinergic terminals. Blockade by the neurotoxin of Ca2+-dependent resting release of transmitter was apparent; Sr2+, Ba2+, or high concentrations of Ca2+ restored the resting release of 3H-catecholamine but not [3H]acetylcholine. Interestingly, none of the latter conditions or 4-aminopyridine could reverse the toxin-induced blockade of evoked release. This lack of specificity in its action on synaptosomes, and other published findings, lead to the conclusion that toxin sensitive component(s) exist in all nerve terminals that are concerned with transmitter release. PMID- 2897429 TI - Characterisation of Na+-independent L-[3H]glutamate binding sites in human temporal cortex. AB - The binding of L-[3H]glutamate to membranes from human temporal cortex was studied in the absence of Na+, Ca2+, and Cl- ions. Pharmacological characterisation revealed that approximately 35% of specific binding at 50 nM L [3H]glutamate was sensitive to a combination of kainate and alpha-amino-3-hydroxy 5-methylisoxazole-4-propionic acid. The remaining approximately 65% of specific binding was to a single population of sites with a KD of 844 nM and a Bmax of 0.92 pmol/mg protein. The pharmacological characteristics were consistent with an interaction at the N-methyl-D-aspartate subclass of excitatory amino acid receptor. The inclusion of Cl- ions revealed additional glutamate binding; this was sensitive to quisqualate and DL-2-amino-4-phosphonobutyrate, but not to kainate, DL-2-amino-7-phosphonoheptanoate, or alpha-amino-3-hydroxy-5 methylisoxazole-4-propionic acid. PMID- 2897428 TI - Agonist-induced stimulation of inositol phosphates in primary rabbit retinal cultures. AB - Carbachol, noradrenaline, and serotonin stimulated the accumulation of inositol phosphates in a dose-dependent manner and maximally by 172.4%, 71.2%, and 51.6%, respectively, in 3-day-old rabbit retinal cultures. In contrast, dopamine, nicotine, isoproterenol, clonidine, 8-OH-dipropylaminotetralin, and gamma aminobutyric acid were ineffective. In older cultures identified as containing primarily Muller cells, only carbachol and noradrenaline were able to induce a significant stimulatory response. The carbachol-, noradrenaline-, and serotonin induced responses were pharmacologically characterized and shown to be mediated by muscarinic, alpha 1-adrenergic, and 5-hydroxytryptamine2 receptors, respectively. The results of the present study show that primary retinal cultures of 3 days of age give results comparable with those of the intact retina. Furthermore, it is demonstrated for the first time that putative Muller cells in cultures possess functional muscarinic and alpha 1-adrenergic receptors. PMID- 2897430 TI - Selective destruction of cultured dopaminergic neurons from fetal rat mesencephalon by 1-methyl-4-phenylpyridinium: cytochemical and morphological evidence. AB - Dopaminergic neurons in cultures of dissociated cells from fetal rat mesencephalon were exposed to the principal metabolite of the neurotoxin 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenyl-pyridinium ion (MPP+), and several of its structural analogues. At concentrations between 0.01 and 0.1 microM, MPP+ inhibited catecholamine accumulation as visualized by cytofluorescence. Between 0.1 and 10.0 microM, MPP+ resulted in disappearance of tyrosine hydroxylase immunoreactivity without affecting other cells in the cultures. At concentrations higher than 10 microM, MPP+ was toxic to all cells present in the cultures. The effect of low concentrations of MPP+ on catecholamine cytofluorescence of the dopaminergic neurons was partially reversible. The intermediate concentrations produced irreversible structural changes of tyrosine hydroxylase-positive cells, resulting in complete disappearance of these neurons. The morphological changes were specific to the dopaminergic neurons and were not evident in other cells viewed with phase contrast microscopy. Of the structural analogues tested, the 1-ethyl analogue of MPP+ was effective in selectively destroying dopaminergic neurons in our culture system. The antioxidants L-acetyl-carnitine, beta-carotene, and alpha-tocopherol failed to protect against MPP+ neurotoxicity when co-incubated with the toxin. PMID- 2897431 TI - Familial adrenoleukodystrophy: long chain fatty acid levels and analysis with a factor VIII DNA probe. AB - Segregation studies of X-linked adrenoleukodystrophy (ALD) and a cloned desoxyribonucleic fragment (factor VIII gene), which detects polymorphism in the distal end of the long arm of the X chromosome (Xq28), are reported in a large sibship ALD family. The findings should permit better identification of carriers and add a new marker for identifying the ALD gene itself. PMID- 2897432 TI - Effect of benzodiazepines on older women. PMID- 2897434 TI - The effects of acetylcholine on response properties of cat somatosensory cortical neurons. AB - 1. Two-hundred thirty-three single neurons were isolated and studied in somatosensory cortex of cats anesthetized with pentobarbital sodium or urethane. Two-hundred and three were studied during iontophoretic administration of acetylcholine (ACh), 173 during administration of glutamate, and 24 during administration of atropine. 2. Fifty-six percent of the 218 neurons tested responded to somatic stimuli. Another 21% did so during glutamate administration. In 11 cases ACh iontophoresis uncovered a receptive field in a previously unresponsive cell. 3. Forty-six percent of the 160 cells tested responded to thalamic stimulation. Another 17% did so in the presence of glutamate, but 19 cells responded to neither cutaneous nor thalamic stimuli. 4. Sixteen percent of the 203 cells tested were overtly excited by ACh and the responses to somatic stimulation of 29% were modulated by administration of ACh. Cells displaying overt excitation and/or modulation of responses were said to be cholinoceptive and made up 39% of the sample. These cells were located in all cortical layers. 5. Cholinoceptive neurons were more likely than noncholinoceptive cells to be driven by thalamic stimulation. 6. The changes observed during ACh administration tended to be facilitatory: an enhanced responsiveness to somatic stimuli, an increased firing rate, or an increased receptive-field size. However, in 10 of the 203 cases tested one or more of these variables decreased. 7. The enhanced responsiveness during ACh administration was a robust phenomenon; responses were often increased by as much as 200% and the discharge pattern was altered so that bursts of impulses following stimulation were more common. 8. ACh tended to enhance one attribute of a cell selectively rather than to act as a general excitant. 9. ACh is a powerful neuromodulatory agent in somatosensory cortex that, when released in specific behavioral states, should enhance the responsiveness of cortical neurons. PMID- 2897435 TI - Transient and prolonged effects of acetylcholine on responsiveness of cat somatosensory cortical neurons. AB - 1. Two-hundred and seven neurons were examined for changes in their responsiveness during the iontophoretic administration of acetylcholine (ACh) in barbiturate-anesthetized cats. 2. The laminar locations of 78 cells were determined. Cholinoceptive neurons were found in all cortical layers and ranged from 50% of the cells tested in layer I to 78% in layer VI. 3. When the responsiveness of a neuron was measured by the magnitude of the discharge generated by a fixed dose of glutamate, 30 of 47 cases (64%) were potentiated, and 4 (8%) were depressed when ACh was administered during glutamate-induced excitation. 4. ACh administered during glutamate excitation was significantly more effective in altering neuronal responsiveness than was ACh administered alone (P less than 0.001). 5. When the responsiveness of a neuron was measured by the magnitude of the discharge generated by a standard somatic stimulus applied to the receptive field, 42 of 52 cases (81%) were potentiated during ACh application. This was again different from ACh treatment alone where only 4 of 27 tests (15%) resulted in subsequent enhancement of the response to somatic stimuli. 6. ACh generally increased the responsiveness of neurons with peripheral receptive fields and caused the appearance of a receptive field in some cells lacking one. 7. In many cases the changes in excitability, as measured by responses either to glutamate or to somatic stimulation, remained for prolonged time periods. When glutamate was used to test excitability, 34% (16 of 47) of the enhancements lasted more than 5 min. When somatic stimuli were used 29% (15 of 52) lasted more than 5 min. With both measures some neurons still displayed enhanced responses more than 1 h after the treatment with ACh. 8. ACh appears to act as a permissive agent that allows modification of the effectiveness with which previously existing afferent inputs drive somatosensory cortical neurons. 9. This mechanism to alter neuronal responsiveness has many of the characteristics necessary to account for the reorganization observed in somatosensory cortex following alterations in its afferent drive and may be related to some forms of learning and memory. PMID- 2897436 TI - Sipple's syndrome with liver tumors examined by iodine-131 MIBG and technetium 99m(V)-DMSA. AB - This case report describes the localization and categorization of tumors using 99mTc(V)-dimercaptosuccinic acid and [131I]metaiodobenzylguanidine scans in a very uncommon case of medullary thyroid carcinoma associated with pheochromocytoma (Sipple's syndrome) and hepatocellular carcinoma. Technetium 99m(V)-dimercaptosuccinic acid showed accumulation only in medullary thyroid carcinoma, but [131I]metaiodobenzylguanidine scans were positive in both medullary thyroid carcinoma and pheochromocytoma. In advanced Sipple's syndrome, combined use of [99mTc(V)]dimercaptosuccinic acid and [131I]metaiodobenzylguanidine may be useful for the categorization of tumor mass lesions and planning appropriate therapy. PMID- 2897433 TI - Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial. AB - From February 1983 to January 1985, 497 patients with advanced breast cancer were randomly allocated to receive either epirubicin or doxorubicin in the following combination chemotherapy regimen: fluorouracil (5-FU) 500 mg/m2 intravenous (IV) on days 1 and 8; epirubicin or doxorubicin 50 mg/m2 IV on day 1; cyclophosphamide 500 mg/m2 IV on day 1 (FEC or FAC). Cycles were repeated every 21 days until progression or to cumulative doses of 700 mg/m2 for epirubicin and 550 mg/m2 for doxorubicin. Dose reductions were applied according to the standard criteria. Activity was evaluated in 443 patients (222 in the FEC arm and 221 in the FAC arm). The two experimental groups were comparable in age, performance status, menopausal status, histology, previous treatments, and site of the disease. The overall response rate (complete response and partial response [CR + PR]) was not significantly different: 53.6% for FEC and 56.5% for FAC. The median time to progression was 273 days for FEC and 314 days for FAC; the median survival time was 591 and 613 days, respectively. Leukopenia, anemia, nausea, and vomiting were significantly lower in patients treated with FEC. As for cardiotoxicity, four cases of congestive heart failure (CHF) were recorded among patients treated with FAC while only one was observed in the FEC group. These results indicate that epirubicin in a combination chemotherapy regimen is as active as doxorubicin and is significantly less toxic. PMID- 2897437 TI - Effects of selenium and vitamin E status on plasma creatine kinase activity in calves. AB - In four experiments, attempts were made to induce nutritional myopathy in calves given a selenium- and vitamin E-deficient diet (less than 0.01 mg Se/kg, less than 2 mg total vitamin E/kg). In housed calves, combined selenium and vitamin E deficiency was insufficient to provoke the large increase in plasma creatine kinase activity typical of muscle damage. Such increases were only obtained when selenium- and vitamin E-deficient calves were turned out from indoor housing in small pens to open pasture. The rises in plasma creatine kinase activity on turnout were prevented when the calves had consumed diets supplemented with 0.1 mg Se/kg (as Na2SeO3). The percentage of the polyunsaturated fatty acid, linolenic acid (18:3 omega 3), in plasma total fatty acids was up to 10-fold higher in calves consuming fresh grass at pasture or indoors than in those housed indoors and fed purified diet. However, in the housed calves there were no rises in plasma creatine kinase activity, whereas large increases occurred in those turned out to pasture. Thus, because increased dietary polyunsaturated fatty acid at turnout is not the sole trigger for the development of myopathy in selenium- and vitamin E-deficient calves, additional unidentified dietary or environmental factors must also be involved. PMID- 2897438 TI - Continuous subcutaneous infusion of narcotics using a portable disposable pump. PMID- 2897439 TI - Dose-dependency in the exsorption of theophylline and the intestinal dialysis of theophylline by oral activated charcoal in rats. AB - The elimination half-life of theophylline in serum after intravenous (i.v.) administration of aminophylline increased with increase in dose. Exsorption of theophylline from blood to the gastrointestinal tract was investigated after i.v. administration of aminophylline (10-50 mg kg-1) to rats by the in-situ single pass perfusion technique. The exsorption rate of theophylline into the intestinal lumen also increased with increase in dose. When the dose of aminophylline was increased five-fold from 10 to 50 mg kg-1, the amount of theophylline exsorbed in 120 min was proportionally increased from 450 to 2300 micrograms. The average extent of theophylline exsorbed into the intestinal lumen was 12-15% after doses from 10-50 mg kg-1, while the extent of the drug excreted into the bile varied from 0.17-0.30% after doses from 10-50 mg kg-1. However, intestinal and biliary clearance of theophylline did not change significantly in the range 10 to 50 mg kg-1. Oral administration of multiple doses of activated charcoal reduced the serum theophylline levels after i.v. administration of aminophylline (50 mg kg-1) to rats. The serum half-life and the area under the serum concentration-time curve of theophylline were decreased to 52 and 50% by the charcoal treatment, respectively, while the total body clearance of the drug was increased to 188% compared with the corresponding control experiments. The volume of distribution was not significantly different between treated and control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897440 TI - Involvement of prostaglandins in histamine-induced fluid and electrolyte secretion by rat colon. AB - Histamine increased the transmural potential difference across rat colon in-vivo and induced a net secretion of fluid. Both effects were inhibited by indomethacin. Histamine increased the potential difference and short-circuit current, and reduced tissue resistance in colonic sheets in-vitro. This response was reduced in the absence of chloride in the bathing medium or in the presence of serosal frusemide, suggesting that histamine stimulated electrogenic chloride secretion by the colon. The rise in short-circuit current induced by histamine was calcium-dependent since it was reduced in the absence of serosal calcium or in the presence of serosal verapamil. Indomethacin, a cyclo-oxygenase inhibitor, and mepacrine, a phospholipase inhibitor, both caused a dose-dependent inhibition of the electrical response of colonic sheets to histamine, without affecting the rise in short-circuit current induced by prostaglandin E2. The stimulation of chloride secretion induced by histamine in rat colon therefore appears to be mediated by an increased production of prostaglandins. PMID- 2897441 TI - Interaction of memantine with cholecystokinin receptors in mouse brain. AB - The effect of memantine on CCK receptors in mouse brain has been investigated using particles of dissected cortex and striatum. Total binding of radio-labelled CCK33 was one-half maximal within 10 min of incubation and reached a maximum after 30 to 60 min when either cortex or striatum was used. Non-specific binding (presence of 100 microM unlabelled CCK8) was 50 to 80% of total binding at steady state conditions. CCK8 inhibited specific binding of radiolabelled CCK33 in a dose-dependent manner; the IC50 (half-maximal inhibitory concentration) was in the range 3 to 4 nM. Memantine increased CCK binding in a concentration-dependent manner, though at high concentrations. The EC50 (half-maximal effective concentration) of this effect was less than 100 microM. The memantine effect is not due to an inhibition of labelled CCK degradation in the medium. The effect of memantine on CCK binding is unique for brain since it was not observed in pancreatic acinar membranes. These data, therefore, suggest a modulatory effect of memantine on CCK receptors in mouse brain (cortex and striatum) particles. PMID- 2897442 TI - The effect of metoclopramide on the absorption and pharmacology of chlorpromazine in the rat. AB - The mechanism of interaction between metoclopramide (MCP) and chlorpromazine (CPZ) has been examined in rats. MCP given intraperitoneally 30 min before orally administered CPZ significantly enhanced the cataleptic and hypothermic effects of CPZ, and also initially increased its plasma and brain concentrations. However, MCP had no effect on the plasma and brain concentrations of CPZ given as an intravenous bolus, indicating that MCP interacts with CPZ during its intestinal absorption. Furthermore, co-administration of MCP (i.p.) with CPZ (p.o.) markedly accelerated gastric emptying compared with CPZ alone, and MCP (i.v.) did not alter the uptake of CPZ by the intestinal membrane. Therefore, it is concluded that MCP causes an increase in the rate of CPZ absorption, by accelerating the gastric emptying. PMID- 2897443 TI - Different ability of trifluoperazine to inhibit agonist-induced contraction of lung parenchyma strips from control and sensitized guinea-pigs. AB - There is increasing interest in the therapeutic potential of calcium antagonists in asthma. Among them the use of calmodulin antagonists deserves consideration. In the present work the effect of trifluoperazine on contractions generated by different mechanisms (CaCl2, KCl, acetylcholine, histamine and 5 hydroxytryptamine) in lung parenchyma strip isolated from control and actively sensitized guinea-pigs has been studied. Trifluoperazine produced both in unsensitized and sensitized lung strips, a concentration-dependent, right, downward displacement of the concentration-response curves to the agonists used, although the sensitization procedure resulted in a potentiation in the ability of trifluoperazine to inhibit agonist-induced contractions. The basis for this greater potency of trifluoperazine in sensitized tissues remains to be elucidated but raises attention to the future use of selective calmodulin antagonists in the management of asthma. PMID- 2897444 TI - The influence of binder film thickness on the mechanical properties of binder films in tension. AB - The physicomechanical properties of films of different thicknesses, made from methylcellulose and gelatinized maize starch, have been studied in tension. There was a linear relation between film thickness and tensile strength, toughness, elastic resilence and elongation at fracture. Young's modulus increased with decreasing film thickness particularly with films with a thickness of less than 15 micron. PMID- 2897445 TI - The permeability of grafted human transplant skin in athymic mice. AB - Human skin has been transplanted onto athymic mice and its permeability properties assessed to see if this in-vivo model would be of benefit in predicting accurately absorption of drugs or toxic chemicals through human skin. The permeability properties of the skin alone, and grafted and athymic mouse skin were assessed by measuring in-vitro absorption of tritiated water and a permanently charged cationic penetrant, paraquat. The grafted skin and athymic mouse skin had similar permeability to the tritiated water. However, the grafted skin was less permeable to paraquat but was more permeable to it than normal human skin, indicating that although histologically, the transplanted skin appeared normal, its barrier properties were impaired. The model was not, therefore, useful for assessing human percutaneous absorption. PMID- 2897446 TI - Lipid solubility of a series of drugs and its relevance to fatal poisoning. AB - For 11 commonly used drugs, the n-octanol/water partition coefficient (pH 7.4 temperature 37 degrees C) and solubility in n-octanol were determined. The drugs tested were chlorpromazine, amitriptyline, trazodone, dextropropoxyphene, diltiazem, dibucaine, amethocaine, procaine, quinidine, acetylsalicylic acid and paracetamol. For eight of the drugs, the relative lipid saturation corresponding to a fatal plasma concentration was estimated from the two parameters determined above and the median fatal blood concentrations reported in the literature. For five of those eight drugs, the estimated relative saturation in the lipid phase fell within the range 0.001-0.004 which is close to relative saturation figures in aqueous and vapour phases already published for chemicals possessing a non specific or physical mechanism of toxicity. Since this is determined largely by their lipid solubility, it is probable that accumulation in the lipid phase is an important determinant of the lethal toxicity of drugs and chemicals with a non specific mechanism of toxicity. PMID- 2897447 TI - Inhibition of the cataleptic effect of tetrahydrocannabinol by other constituents of Cannabis sativa L. AB - Tetrahydrocannabinol (THC) induced catalepsy in mice, whereas a cannabis oil (6.68% w/w THC), four cannabinoids and a synthetic mixture did not. Cannabinol (CBN) and olivetol inhibited THC-induced catalepsy in the mornings and the evenings, but cannabidiol (CBD) exhibited this effect only in the evenings. A combination of CBN and CBD inhibited THC-induced catalepsy equal to that of CBN alone in the mornings, but this inhibition was greater than that produced by CBN alone in the evenings. PMID- 2897448 TI - Age-dependent pulmonary first-pass elimination of propranolol in rats. AB - Plasma levels of propranolol after 2.5 mg kg-1 given i.v. and i.a. have been compared in 3- to 4-week-old rats to evaluate the effect of age on pulmonary first-pass elimination of the drug. In 5- to 52-week-old rats, the area under the plasma concentration-time curve (AUC) after an intra-arterial dose was always larger than that after the i.v. dose. The plasma elimination half-lives after both routes of administration were almost identical, but tended to increase with age between weeks 7 and 104. First-pass pulmonary clearance and extraction ratio tended to decrease with age between weeks 7 and 52. PMID- 2897449 TI - Agonist profile of ergometrine (ergonovine) on a population of postsynaptic alpha adrenoceptors. AB - Ergometrine (0.02-5 microM) produced concentration-related contractions of the mouse anococcygeus muscle, which were unaffected by cocaine (2 microM) or by pretreatment of mice with 6-hydroxydopamine. Contractions were reduced by alpha adrenoceptor antagonists; the rank order of potency was prazosin greater than phentolamine greater than yohimbine. With phenoxybenzamine as antagonist, the estimated dissociation constant (KD) for ergometrine was 0.41 microM. It is concluded that ergometrine causes direct activation of postsynaptic alpha 1 adrenoceptors, and it is suggested that it acts on the same subtype of the receptor as imidazoline agonists. PMID- 2897450 TI - Determination of rat cerebrospinal fluid concentrations of adenosine, inosine, hypoxanthine, xanthine and uric acid by high performance liquid chromatography. AB - Isocratic reverse-phase high performance liquid chromatography techniques were developed to resolve and quantitate the purine nucleosides adenosine (Ado) and inosine (Ino) and their metabolites hypoxanthine (Hyp), xanthine (Xan), and uric acid (UA) in the cerebrospinal fluid of the rat. The moving phase composition for resolving hypoxanthine, xanthine and uric acid was a 0.22 M, pH 5.8 phosphate buffer. The moving phase composition for resolving adenosine and inosine was a 0.22 M, pH 6.8 phosphate buffer, 7% methanol (v/v) and 2.5 mM tetrabutylammonium phosphate. The observed cerebrospinal fluid concentrations in the rat were: Ado = 35 +/- 9 nM (s.e.m.), Ino = 359 +/- 85 nM, Hyp = 243 +/- 77 nM, Xan = 1340 +/- 423 nM and UA = 6130 +/- 678 nM. PMID- 2897451 TI - The emetic activity of centrally administered cisplatin in cats and its antagonism by zacopride. AB - Cisplatin administered by either the intravenous (i.v.) or intra cerebroventricular (i.c.v.) route produced emesis in cats. The average time to onset of emesis was decreased significantly (4.0 min versus 100.6 min) when cisplatin was administered i.c.v. Zacopride administered either i.c.v. (0.02 mg) or i.v. (0.1 mg kg-1) completely blocked the emesis due to cisplatin given by either route. Their data show that cisplatin possesses a central emetic component and that this is blocked by zacopride. PMID- 2897452 TI - Inhibition of thromboxane biosynthesis by 3-pyridinol carboxypentyl ethers substituted with a hydroxylated octyl chain. AB - Racemic 6-[4-(3'-hydroxy-1'-octenyl)-3-pyridyloxy]hexanoic and 6-[4-(3' hydroxyoctyl)-3-pyridyloxy] exanoic acids have been synthesized and their activity as inhibitors of the biosynthesis of thromboxane A2 in human serum has been studied, in comparison with isomers having the eight-carbon chain in the 2 position. Very high, selective activity was found for the new 4-substituted 3 pyridinol ethers, whereas the 2-substituted compounds showed no action. PMID- 2897453 TI - Action of mefloquine on toad isolated rectus abdominis muscle. AB - The effects of mefloquine and quinine on acetylcholine-induced contractures of the toad rectus abdominis muscle have been investigated. Both drugs depressed acetylcholine-induced contractures in a dose-related and non-competitive manner. A partial reversal of the block was observed in the presence of 4-aminopyridine (10, 50 microM) and increased Ca2+ content (1.25x) of the Ringer solution. In both cases, the mefloquine-induced blockade was more readily reversed than that induced by quinine. Mefloquine and quinine at concentrations greater than 100 and 500 microM, respectively, also elicited a direct contractile response on the muscle. Quantitative differences in their contractile activity have been attributed to the greater lipid solubility and tissue binding affinity of mefloquine. PMID- 2897454 TI - A selective inhibitor of cAMP-specific phosphodiesterase, Ro 20-1724, has no effect on the quantal release of acetylcholine from the mouse phrenic nerve. AB - The indirect twitch response of the mouse isolated phrenic nerve-diaphragm preparation, partially paralysed by tubocurarine, was restored only by about 10% by Ro 20-1724 at 2 to 280 microM. The solvent vehicle, dimethylsulphoxide, also showed the same effect to a similar extent. Intracellular recordings with glass microelectrodes revealed that Ro 20-1724 (40 microM) affected neither the resting membrane potential, the amplitude and frequency of miniature endplate potentials nor the amplitude of nerve-impulse evoked endplate potentials recorded in curarized preparations. The result indicates that Ro 20-1724 at a concentration four times the IC50 of phosphodiesterase inhibition has no effect on the quantal release of acetylcholine from a mammalian motor nerve and suggests that cAMP has no modulatory effect on the transmitter release. PMID- 2897455 TI - Effect of sodium valproate on midazolam distribution. AB - The displacement of midazolam, a new water-soluble, short acting benzodiazepine, from its plasma binding sites by sodium valproate, has been studied in man. An increase of its free fraction (ranging from 2.71 to 5.35%) in plasma from epileptic patients receiving sodium valproate was observed. A similar situation was created in rabbits by pretreatment with sodium valproate (600 mg kg-1 day-1) and posterior hypnosis with midazolam. Due to the interaction, sodium valproate pretreated rabbits showed an increase in midazolam brain levels (130.91 micrograms g-1 in cortex vs 84.55 micrograms g-1 in control animals). Therefore, it seems likely that displacement of midazolam by sodium valproate in epileptic patients could lead to an increase of the midazolam response. PMID- 2897456 TI - N-methylation of nicotine enantiomers by human liver cytosol. AB - Incubation of human liver cytosol with either R-(+)-[3H-N'CH3]nicotine or S-(-) [3H-N'CH3]nicotine results in the formation of the corresponding N-methyl quaternary ammonium metabolite. A substrate stereoselectivity was observed in that the turnover number for the methylation of the S-(-)-isomer was 0.25 pmol mg 1 protein h-1, whereas that for the R-(+)-isomer was 2.11. The latter substrate exhibited an apparent Km value of 20.1 microM. Nicotine N-methylation appears to be species-dependent, since rat liver homogenates contained no 'nicotine N methyltransferase' activity, whereas with guinea-pig liver homogenates, a substrate specificity for only R-(+)-nicotine was observed. PMID- 2897457 TI - Repeated treatment with imipramine and amitriptyline reduced the immobility of rats in the swimming test by enhancing dopamine mechanisms in the nucleus accumbens. AB - Bilateral injections of 1 microgram sulpiride in the rat nucleus accumbens antagonized the effect of a seven-day treatment with 20 mg kg-1 day-1 imipramine or amitriptyline in the swimming test. The data suggest that dopamine mechanisms in the limbic regions of the rat brain are involved in the effect of repeated treatment with imipramine and amitriptyline in that test. PMID- 2897458 TI - Solubilization of vitamin K1 by bile salts and phosphatidylcholine-bile salts mixed micelles. AB - The solubilization of vitamin K1 by bile salts (sodium deoxycholate, sodium cholate and their corresponding glycine conjugates) and phosphatidylcholine (egg) bile salt mixed micelles has been investigated. The solubilization curves were not always linear with increasing bile salts, but the vitamin was appreciably solubilized in the region below their CMCs. In the bile salt solutions (20 mM, phosphate buffered saline, pH 7.5, ions strength 0.2), the solubilized vitamin ranged from 0.3 to 0.9 mM. With increasing phosphatidylcholine, the amount of vitamin solubilized was dramatically increased; at the molar ratio of 1:1 (both 20 mM), the amount of vitamin solubilized was about 25-30 times more than by the corresponding bile salts alone. There is a possibility that exogenous phospholipid given orally as liposomal forms assists the solubilization of vitamin K1, in the intestine. This characteristic is suggested as being responsible, in part, for the enhanced recovery of blood coagulation after oral administration of liposomal vitamin K1 to warfarin-treated rabbits. PMID- 2897459 TI - Compatibility of intravenous fat emulsions with prodrug amino acids. AB - Three prodrugs, N-alpha-acetyl-L-arginine, N-alpha-acetyl-L-histidine and N-alpha acetyl-L-lysine have been examined to see if they could induce significant changes in the stability of an intravenous fat emulsion, the stability being evaluated in terms of physicochemical measurements such as particle size distribution, surface tension, pH and zeta potential. The acetyl amino acids had an excellent stabilizing effect on the emulsion compared with amino acids without acetyl groups. PMID- 2897460 TI - Variation of population release kinetics in polydisperse multiparticulate systems (microcapsules, microspheres, droplets, cells) with heterogeneity of one, two or three parameters in the population of individuals. AB - Release kinetics of active substances from ensembles of microparticles such as microcapsules, cells, droplets and liposomes constituted of individual entities releasing their contents at constant rates may follow zero order, first order, sigmoid or biphasic equations. The release equation observed depends upon the statistical distribution of release-determining parameters among the population. Typical cases are presented in terms of the distribution of two parameters, payload (m infinity) and time for complete payload release (t infinity) which also define the release rate constant (k). Heterogeneity of the two parameters generally leads to first order ensemble behaviour, whereas heterogeneity of one parameter only may lead to different ensemble release equations, viz. zero order (m infinity heterogeneous) or first order (t infinity heterogeneous). Biphasic distribution can lead to an apparent 'burst' effect, with apparent change of kinetics. The presence of a third heterogeneous parameter, lag time, yields a sigmoid ensemble release curve. These conclusions are demonstrated by simulations or experimentally, and are also valid for linearized curves of microparticles following matrix kinetics. PMID- 2897461 TI - Differential retention of doxorubicin in the organs of two strains of rats. AB - Fluorescence microscopy and high pressure liquid chromatography were used to study the decrease of doxorubicin (DXR) concentrations in the liver, spleen, heart, lung, kidney and skeletal muscle of two strains of rats at various times after a single intravenous injection of the drug (8 mg kg-1). DXR was located within the cell nucleus and was mostly undegraded, it persisted, especially in heart, lungs and spleen where it was detectable 10 days after injection. The DXR/DNA ratio, was used as an index of nuclear fixation of the drug. A major difference in the DXR/DNA ratio between the two strains were observed in heart and spleen results; the DXR/DNA ratio was significantly higher in heart and spleen compared with lung, liver and kidney in both strains. PMID- 2897463 TI - Ontogeny of somatostatin binding sites in the rabbit small intestinal epithelial tract. AB - The ontogenic patterns of somatostatin content and its binding sites were studied in small intestine in the developing rabbit from birth until the adult stage. A peak of somatostatin concentration was observed immediately after birth (day 0) and at day 10 in duodenum and jejunum, followed by a decrease at day 15 and a new and gradual augment thereafter. Ileal somatostatin concentrations decreased after birth up to day 15 and then increased progressively with age until the adult period. The somatostatin binding capacity in cytosol of the mucosal layer of duodenum, jejunum and ileum decreased from birth until 10 days and increased thereafter up to the adult period. However, no age differences in dissociation constants were observed. Interestingly, there was an apparent lack of high affinity sites immediately after birth (day 0) whereas two classes of binding sites were seen thereafter. These results suggest that somatostatin may be involved in the functional and anatomical development of the small intestine during the neonatal period. PMID- 2897462 TI - Etintidine-propranolol interaction study in humans. AB - Etintidine HCl is a potent H2-blocker. The effect of clinical doses of etintidine on the disposition of a single oral dose of propranolol was investigated in 12 normal subjects. This was a double-blind, two-way crossover study. Each subject received etintidine (400 mg) or placebo twice a day with meals for 4 days on two occasions (separated by 4 days). On each occasion, the subjects were fasted overnight on Day 3 and were given an oral dose of Inderal (40 mg propranolol hydrochloride) 30 min following the administration of the morning dose of etintidine or placebo on Day 4. Blood samples were collected prior to and up to 24 hr following the administration of propranolol. The plasma samples were analyzed for propranolol and 4-hydroxypropranolol by HPLC. Comparison of the pharmacokinetic parameters of propranolol between etintidine and the placebo groups indicates that etintidine significantly increased the AUC0-infinity values (573.5 vs. 146.4 ng.hr/ml, p = 0.0001) and prolonged the elimination half-life (4.61 vs. 2.33 hr) of propranolol. Statistical evaluation of the pharmacokinetic parameters of 4-hydroxypropranolol indicates that etintidine also increased the AUC0-24 values (43.8 vs. 16.4 ng.hr/ml, p = 0.0028) and prolonged the elimination half-life (4.87 vs. 1.97 hr) of 4-hydroxypropranolol. The data suggest that etintidine, like cimetidine, impaired the elimination of propranolol. Etintidine also protracted the elimination of 4-hydroxypropranolol, an active metabolite of propranolol. PMID- 2897465 TI - Economic aspects of beta-blocker therapy following myocardial infarction. PMID- 2897464 TI - Reversible pulmonary disease and eosinophilia associated with sulphasalazine. PMID- 2897466 TI - Synthesis and oral antiallergic activity of carboxylic acids derived from imidazo[2,1-c][1,4]benzoxazines, imidazo[1,2-a]quinolines, imidazo[1,2 a]quinoxalines, imidazo[1,2-a]quinoxalinones, pyrrolo[1,2-a]quinoxalinones, pyrrolo[2,3-a]quinoxalinones, and imidazo[2,1-b]benzothiazoles. AB - 4H-Imidazo[2,1-c][1,4]benzoxazine-2-carboxylic acid (3) was found to possess potent activity in the IgE-induced rat passive cutaneous anaphylaxis model which may be predictive of clinical antiallergic activity. Compared to disodium cromoglycate (DSCG, 1), 3 was less active following iv administration but unlike DSCG showed very significant oral activity. To explore the structural requirements for this activity, a range of tricyclic compounds was prepared and their activities were measured. Individual 2-carboxylic acids derived from imidazo[1,2-a]quinolines, imidazo[1,2-a]quinoxalines, imidazo[1,2 a]quinoxalinones, pyrrolo[1,2-a]quinoxalinones, pyrrolo[2,3-a]quinoxalinones, and imidazo[2,1-b]benzothiazoles showed iv activities up to 10(3) times as potent as DSCG and many of them showed significant oral activity. From these, imidazo[1,2 a]quinoxaline-2-carboxylic acid 114 has been chosen for further development. PMID- 2897467 TI - Binding of steroids to the progestin and glucocorticoid receptors analyzed by correspondence analysis. AB - The relative binding affinities of over 30 steroids have been measured for the cytosol glucocorticoid receptor (GR) of thymus, liver, and hepatoma tissue culture cells and for progestin, androgen, and mineralocorticoid receptors. The data have been analyzed by correspondence analysis to reveal the singularities among the receptors of different hormonal classes, the similarities in GR of different origins, and the different specificities of the ligands. Additional data on new steroids have been injected into the system as well as results on a further parameter, namely the induction of tyrosine aminotransferase (TAT) activity, to illustrate the power and flexibility of the methodology. The analysis has confirmed previous correlations between GR binding and TAT response but also highlighted the antiglucocorticoid activity of progestins. This method should prove to be a substantial aid to the interpretation of increasingly complex data, in particular with regard to the action of existing and newly synthesized steroids on glucocorticoid systems of differential sensitivity. PMID- 2897468 TI - (Imidazo[1,2-a]pyrimidin-2-yl)phenylmethanones and related compounds as potential nonsedative anxiolytics. AB - Several series of heterocyclic carboxylic esters were found to be active in the benzodiazepine receptor binding assay, a typical example being ethyl 7-ethyl-5 methoxyimidazo[1,2-a]quinoline-2-carboxylate (4b) with an IC50 of 150 nM. The corresponding phenylmethanone 5d was more potent with an IC50 of 14 nM and was orally active in animal models thought to predict anxiolytic effects. The synthesis of a large number of compounds resulted in the optimization of this activity in a series of (imidazo[1,2-a]pyrimidin-2-yl)phenylmethanones of which compounds 7e, 8b, 8h, 8j, and 8k were equipotent with chlordiazepoxide while exhibiting reduced anticonvulsant activity, little or no muscle relaxation, and negligible sedative effects. PMID- 2897469 TI - Increasing correspondence between test items and objectives as part of a physician assistant curriculum evaluation. PMID- 2897470 TI - Adhesion of clinical and environmental Aeromonas isolates to HEp-2 cells. AB - A total of 63 Aeromonas strains isolated from diarrhoeal faeces or water samples were tested for adhesion to HEp-2 cells. An association between diarrhoea and high level adhesion was observed in that 12 of the 34 faecal isolates and none of the 29 environmental isolates yielded greater than 20 bacteria per HEp-2 cell in the adhesion assay. The proportion of high adherers was significantly greater for A. sobria (57%) than for A. hydrophila isolates (19%). Three of the eight faecal A. caviae isolates were also found to be high adherers. All of the environmental isolates were heavily pilated with pili having a mean diameter of 5 nm and a mean length of 420 nm; these were termed type-S pili. Of the 34 faecal isolates, 32% possessed S pili, and 68% were lightly pilated with up to 15 thin, flexible type L pili, of mean diameter 2.5 nm and mean length 960 nm. Type-L pilation was associated with a high level of HEp-2 cell adhesion, and was more common in A. sobria and A. caviae than in A. hydrophila isolates. These results suggest that adherence to HEp-2 cells is a useful model for the investigation of Aeromonas enteropathogenicity, and that adhesion may be pilus-mediated in this organism. PMID- 2897471 TI - T lymphocyte subpopulations and immunoglobulin-containing cells in the colonic mucosa of ulcerative colitis; a morphometric and immunohistochemical study. AB - T lymphocyte subpopulations and immunoglobulin containing cells in the colonic mucosa of 25 patients with ulcerative colitis have been studied using an indirect immunoperoxidase technique. In ulcerative colitis a marked increase in the population of Leu 3a positive cells (helper/inducer T cells) and IgG containing cells was observed in the mucosal lamina propria. In the intraepithelial spaces, a remarkable decrease in the population of Leu 2a positive cells (suppressor/cytotoxic T cells) and a marked increase in the number of Leu 3a positive cells were revealed. There was a very significant correlation between the population of IgG containing cells and the ratio of Leu 3a positive cells to Leu 2a positive cells in the lamina propria of patients with ulcerative colitis. These results suggest that an imbalance of mucosal immunoregulatory T cells and an increased production of IgG occurred in correlation with inflammatory activities of ulcerative colitis. PMID- 2897472 TI - Variation in indirect cell-mediated lympholysis. AB - The ability of an allograft recipient to respond to donor mononuclear cells in an indirect cell-mediated lympholysis (ICML) assay is an in vitro correlate of allograft rejection, but the value of this correlation depends upon the assay's reliability. We had observed inconsistency in the cytotoxic response of normal human mononuclear cells (MNC) to the same allogeneic stimulator MNC when cytotoxicity was measured repeatedly on different occasions by micro-ICML. We, therefore, investigated the extent and reasons for this inconsistency. Method variation, determined by duplicate ICML of 18 stimulator: responder MNC, was not statistically significant. Variation in cytotoxicity over time was greater but still not statistically significant. The contribution to method variation of 51Cr release from 3 different sets of target cells, cultured and labeled in duplicate, was minimal (6.33%). We then asked if in vitro generation of effector MNC under laboratory conditions was a major cause of ICML variation. We tested this using a stable transplant's in vivo sensitized effector cells against donor MNC in a direct CML (DCML) and obtained consistent results. Finally, to gain an understanding of some of the factors which might influence the generation of in vitro cytotoxicity, we measured the frequencies of cell surface antigens (DR, TAC, transferrin, Leu 2 and 3) concomitantly with ICML on day 6 of culture. Statistical analysis of the results led us to conclude that the micro-ICML is reproducible. The magnitude of lysis depends upon activated target cells (TAC- and transferrin-positive) and an increase in the proportion of helper/inducer to cytotoxic/suppressor T-lymphocytes during effector cell generation. PMID- 2897473 TI - Crystallization and preliminary diffraction data for adenosylcobalamin-dependent methylmalonyl-CoA mutase from Propionibacterium shermanii. AB - Pink crystals of methylmalonyl-CoA mutase from Propionibacterium shermanii, a coenzyme B12 (5'-deoxyadenosylcobalamin)-dependent enzyme, have been obtained by the hanging-drop method in two different forms. One form lies in the space group P21, with unit cell dimensions a = 122 A, b = 160 A and c = 90 A, with beta = 104 degrees (1 A = 0.1 nm). There are two alpha beta dimers in the asymmetric unit. The crystals diffract to 3.2 A resolution and are suitable for high resolution X ray diffraction studies. PMID- 2897474 TI - Adenosine deaminase isoenzymes and HIV/HTLV-1 infections. PMID- 2897476 TI - Ureteropyeloscopic removal of ureteral calculi. AB - Ureteroscopy has been used for the treatment of calculi throughout the ureter. The results of ureteroscopic stone removal were reviewed in 100 patients. Similar results were compared in 30 patients undergoing ureterolithotomy and 32 treated by basket manipulation. Success of ureteroscopic removal was related to the location of the calculus: 50 per cent in the proximal, 80 per cent in the mid and 99 per cent in the distal ureter. Hospital stay, costs and narcotic analgesic use were significantly less for ureteroscopic stone removal than for open surgical lithotomy. The success rate for ureteroscopic removal of distal calculi (99 per cent) was higher than for blind basketing procedures (59 per cent). Ureteroscopy should be considered the technique of choice for the removal of distal ureteral calculi. It is an acceptable alternative for treatment of calculi throughout the urinary tract. PMID- 2897477 TI - A case of pediatric ureteroscopic lasertripsy. AB - The standard treatment for ureteral calculi in children has been open surgical removal. Recently, we removed successfully a lower ureteral calculus in a young child with ureteroscopy and the pulsed dye laser. The improvements in smaller rigid and flexible ureteroscopes, in conjunction with lasertripsy, will expand its applications in the treatment of pediatric urolithiasis. PMID- 2897475 TI - Mechanism of c-erbB transduction: newly released transducing viruses retain poly(A) tracts of erbB transcripts and encode C-terminally intact erbB proteins. AB - We have previously shown that avian leukosis virus (ALV) induces erythroblastosis by insertional activation of the c-erbB gene. In 25% of the ALV-induced leukemic samples we have analyzed, acute retroviruses that have captured the activated erbB oncogene were released. The unusually high frequency at which erbB transduction occurs makes this an ideal system for studying the mechanism of oncogene transduction. In addition, these leukemic samples provide a rich source for the isolation of novel erbB-transducing viruses. We report here our characterization of several new erbB-transducing proviruses. The 5' recombination points of all these viruses mapped to the same intron in which proviral insertions cluster, supporting the hypothesis that transduction begins with proviral insertion near the oncogene. The 3' recombination points usually occurred within the 3' untranslated region downstream from the termination codon of the c-erbB gene. Three of the erbB-containing proviruses were molecularly cloned and analyzed in detail. Two of them were capable of releasing acute viruses, and interestingly, both retained poly(A) tracts of erbB messages in their genomes. A stretch of six adenosine residues in the ALV env gene appeared to mediate the 3' recombination events required for the generation of these viruses. These data provide further insight into the mechanism by which oncogenes are transduced into retroviral genomes. PMID- 2897478 TI - Internal mammary artery coronary bypass and leg ischemia. PMID- 2897480 TI - [Mechanism of recurrence and relapse in peptic ulcer after drug therapy; gastric juice and gastric acid secretion]. PMID- 2897479 TI - The effect of metoclopramide treatment on diabetic cystoparesis. PMID- 2897481 TI - [Drug administration schedule of anti-ulcer agents to prevent recurrence of peptic ulcer; intermittent and long-term administration]. PMID- 2897482 TI - [Recent developments in drugs antagonistic to factors causing peptic ulcer- clinical effects and problems; histamine H2 receptor blockaders]. PMID- 2897483 TI - [Various problems on refractory peptic ulcers; ulcers resistant to therapy with H2-receptor antagonists--therapeutic countermeasures]. PMID- 2897485 TI - [Gastroscopic stage classification of peptic ulcer according to drug therapy- regular and magnification gastroscopy]. PMID- 2897484 TI - [Various problems on refractory peptic ulcers; drug therapy of hemorrhagic peptic ulcers--therapeutic efficacy and limitations]. PMID- 2897486 TI - [Comparative studies on recurrence and relapse rate in peptic ulcer treated with various types of anti-ulcer agent; inhibitors of initiating factors causing peptic ulcer]. PMID- 2897487 TI - [Perspectives in the drug therapy of peptic ulcer]. PMID- 2897488 TI - [Follow-up studies of the tissue healing process in peptic ulcer; clinicopathological study of recurrence refractory conditions in peptic ulcer]. PMID- 2897490 TI - [Changes in hepatic gamma-glutamyl transpeptidase (gamma-GTP) in rats with long term ethanol administration]. PMID- 2897489 TI - [Follow-up studies of the tissue healing process in peptic ulcer; characteristics of the modification of the ulcer-healing process with various types of anti-ulcer agents]. PMID- 2897491 TI - [Impression on the 1st International Home Childbirth Congress (1)]. PMID- 2897492 TI - [The 1st International Home Childbirth Congress: my personal learning experience]. PMID- 2897493 TI - [Impressions of the 1st International Home Childbirth Conference. (2)]. PMID- 2897494 TI - [History of public health nurses affiliated with the Osaka Public Health Office. 6. At the start of the establishment of the office (6). The first Congress of the nationwide organization of public health nurses and public health nursing education before and during the second world war (1)]. PMID- 2897495 TI - [Atypical variant of Cushing's syndrome]. PMID- 2897496 TI - [Countdown to 2000. 2. International conference for primary health care of WHO in London]. PMID- 2897497 TI - [Yearly meeting of the European Nursing Student Group in Essen]. PMID- 2897499 TI - [Knee deformities in patients with Larsen syndrome]. PMID- 2897498 TI - Increase in cytoplasmic free calcium concentration initiated by T3 antigen stimulation is imparied in adult T-cell leukemia cells. AB - We studied the change in cytoplasmic free calcium ion concentration ([Ca2+]i) in the peripheral blood leukemic cells from adult T-cell leukemia (ATL) patients stimulated by anti-T3 (CD3) or anti-T11 (CD2) antibodies in order to see whether there is an abnormal response in the early activation processes following T3 or T11 antigen stimulation. Peripheral blood mononuclear cells (PBMC) from four T cell chronic lymphocytic leukemia (T-CLL) patients showed a rapid and clear increase in [Ca2+]i (from 165 +/- 26 nM to more than 299 nM) when stimulated by OKT3 antibody and anti-mouse IgG antibody. This response was comparable to that of PBMC from 10 normal individuals (from 151 +/- 20 nM to 252 +/- 34 nM). In contrast, PBMC from 10 ATL patients showed only a slight increase in [Ca2+]i (from 137 +/- 21 nM to 176 +/- 32 nM) following T3 stimulation. The experiments with higher concentrations of OKT3 antibody suggested that this attenuated increase in [Ca2+]i in ATL cells was not exclusively due to impaired expression of T3 antigen. The [Ca2+]i increase in ATL cells induced by the stimulation with two anti-T11 antibodies recognizing different epitopes of the T11 antigen, however, was comparable to that of normal PBMC. The abnormal response of [Ca2+]i to the T-cell receptor/T3 antigen stimulation in ATL may be related to dysfunction or leukemogenesis of HTLV-I-infected cells. PMID- 2897500 TI - [Correlation between the blood supply and the function of the fingers]. PMID- 2897501 TI - [Therapeutic aspects of the pathology of burn injuries]. PMID- 2897502 TI - [20 years' experience with the Charnley hip prosthesis. The Wrightington experience]. PMID- 2897503 TI - [The Bristow-(Latajet) operation]. PMID- 2897504 TI - [Damage to the articular cartilage during short-time immobilization in various positions]. PMID- 2897505 TI - [External splint constructed for the fixation of osteotomy in the proximal end of the tibia]. PMID- 2897506 TI - [Concomitant leg injuries considerably influencing rehabilitation of cranio cerebral trauma]. PMID- 2897507 TI - [Rare variation of the ramus muscularis nervi mediani]. PMID- 2897508 TI - [From trauma care at the county level to the founding of the Regional Trauma Center of East Hungary]. PMID- 2897509 TI - [Central carpal bone or double pseudoarthrosis of the navicular bone?]. PMID- 2897511 TI - [Undiagnosed posterior dislocation of the shoulder]. PMID- 2897510 TI - [The use of an isoelastic pelvic prosthesis in segmental resection]. PMID- 2897512 TI - Biology of depression. AB - Research over the past three decades has led to a greater understanding of the biologic basis of depression. Observations that certain medications could improve or worsen mood led to the development of hypotheses describing the possible role of specific neurotransmitters in the brain in depression. Modifications of these original hypotheses focused on altered receptor function, failures in the regulation of neurotransmitter systems, and interactions of the monoamines with cholinergic systems. Strategies using endocrinologic measurements in the evaluation of the depressed patient have provided researchers with new clues regarding disordered neuroendocrine function in depression and clinicians with new tests to aid in diagnosis and management. Moreover, the development of standardized sleep EEG methodology has proven useful for the identification of characteristic sleep abnormalities in depression. Although there are many methodologic and clinical problems still to be resolved, the use of biological markers in the assessment of the depressed patient is increasing, and is likely to be of significant importance in the future. Finally, recent advances in molecular genetics hold promise for further advances in our understanding of the inheritance and biochemistry of depression. PMID- 2897513 TI - Recognizing the drug-resistant patient in anxiety and depression. AB - The number and variety of anxiolytic and antidepressant medications available to the modern clinician lend an unparalleled efficacy to the outpatient treatment of anxiety disorders and depression. Where diagnosis is precise and complicating organic factors have been excluded, true treatment resistance in either anxiety disorders or depression is rare. Proper patient education to assist compliance, adequate dosage of individual agents, patience to give the medication time to work, overcoming the reluctance to attribute the patient's problem to a medically treatable disorder rather than to moral or characterologic defect, and the flexibility to shift to other or to additional medications on encountering initial treatment resistance are the keystones to the successful management of more than 90 per cent of all cases. PMID- 2897514 TI - [After pharmacologic blood pressure treatment: only two in ten male hypertensive patients attain the recommended diastolic pressure]. PMID- 2897515 TI - Comparative efficacy of ceftriaxone and rifampicin in eradicating pharyngeal carriage of group A Neisseria meningitidis. AB - During an outbreak of meningococcal meningitis in Saudi Arabia, oral rifampicin (four doses in two days) was compared with a single intramuscular dose of ceftriaxone for prophylaxis in family contacts of patients with meningococcal disease. Pharyngeal samples were taken for culture before and 1 and 2 weeks after administration. Both follow-up cultures indicated that ceftriaxone was significantly more effective. At 1 week the eradication rates for ceftriaxone and rifampicin were 97% and 75%; at 2 weeks they were 97% and 81%, respectively. No serious side-effects were associated with either agent. Ceftriaxone may provide an effective alternative to rifampicin for prophylaxis in meningococcal contacts. PMID- 2897517 TI - Prevention of post-transfusion non-A, non-B hepatitis by non-specific immunoglobulin in heart surgery patients. AB - To evaluate the effectiveness of immune serum globulin (ISG) in preventing non-A, non-B hepatitis, 291 heart surgery patients who received blood from voluntary donors were randomly assigned to receive either ISG or no additional protection. ISG was given intramuscularly before and 1 week after transfusion. 98 controls and 100 in the ISG group completed the study. Post-transfusion non-A, non-B hepatitis developed in 11 (11.2%) controls but in only 3 (3.0%) of the ISG group (p = 0.0203). 8 (72.7%) of control group with hepatitis had symptoms, and in 5 (45.4%) the disease became chronic. The disease was self-limiting in all 3 ISG patients affected, and only 1 of them had symptoms. Among those with non-A, non-B hepatitis aminotransferase levels were higher in the controls than in the ISG patients. Incubation periods longer than 8 weeks correlated with a tendency for the disease to become chronic. ISG recipients had shorter as well as more homogeneous incubation periods. ISG could be a safe, low-cost means for preventing post-transfusion non-A, non-B hepatitis which does not call for the discarding of donated blood. PMID- 2897516 TI - Randomised comparison of two intensities of oral anticoagulant therapy after tissue heart valve replacement. AB - After tissue heart valve replacement 108 patients were randomised to standard anticoagulant control with rabbit brain thromboplastin (Dade C reagent, therapeutic range 18-24 s; international normalised ratio 2.5-40) and 102 to a less intensive regimen controlled with human brain thromboplastin (Manchester Comparative Reagent, therapeutic range 26-30 s; INR 2.0-2.25). Treatment was continued for three months, outcome measures being major or minor embolism or haemorrhage. 2 patients in each group had major embolic events and 11 in each group had minor embolic events. The 95% confidence intervals on the differences are -3.4% to 3.2% for major embolism and -9.3% to 8.2% for minor embolism. Haemorrhagic complications were significantly more frequent with standard treatment (15 patients) than with the less intensive regimen (6 patients); and of the 5 patients with major haemorrhagic complications, all were in the standard treatment group, again a significant difference. The less intensive regimen is thus no less effective and safer than standard anticoagulant therapy in patients with tissue heart valve replacement. PMID- 2897518 TI - Acute meningo-encephalitis on dose reduction of zidovudine. AB - In a study of treatment by zidovudine in 106 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex, an acute meningo encephalitic illness developed in 4 of 21 patients within 17 days after the dose of zidovudine had had to be reduced because of myelotoxicity. 3 of the 4 patients had previous clinical evidence of HIV encephalopathy. AIDS-related opportunist infection of the central nervous system was excluded. This acute meningo encephalitic illness probably results from an increase in HIV replication following dose reduction. PMID- 2897519 TI - Loss of matrix calcium-binding protein-containing neurons in Huntington's disease. AB - In post-mortem brain specimens from patients dying with a clinical diagnosis of Huntington's disease (HD) immunohistochemistry showed a substantial loss from the neostriatum of neurons containing the calcium-binding protein calbindin 28K. These calbindin neurons, and the straital compartment in which they are sited, are particularly damaged in HD, suggesting that a failure of calcium buffering or homeostasis may contribute to cell death in HD. PMID- 2897520 TI - Limitations of care for very-low-birthweight infants. PMID- 2897521 TI - Direction of postgraduate medical education in the UK. PMID- 2897523 TI - Autoimmune thyroid disease and thyroid antibodies. PMID- 2897522 TI - AIDS in sub-Saharan Africa. PMID- 2897524 TI - Cleft palate and glue ear. PMID- 2897525 TI - Livedo reticularis, porcelain-white scars, and cerebral thromboses. PMID- 2897526 TI - Normal ageing, impaired cognitive function, and senile dementia of the Alzheimer's type: a continuum? AB - There is little evidence to support the view that senile dementia of the Alzheimer's type (SDAT) is distinct from the normal ageing process. The changes in brain function found in normal ageing, benign senescent forgetfulness, and SDAT can be seen as a continuum, which may reflect a single underlying process. The failure to account for this possibility in research design may explain why few risk factors for SDAT have been identified. PMID- 2897528 TI - Coagulation factor VIII concentrates and the marketplace. PMID- 2897527 TI - Rheumatic disease, heavy-metal pigments, and the Great Masters. AB - The painters Rubens, Renoir, and Dufy suffered from rheumatoid arthritis and Klee from scleroderma. Analysis of the areas of various colours in randomly selected paintings by these four artists and by eight "controls" (contemporary painters without rheumatic disease) suggests that Rubens, Renoir, Dufy, and Klee used significantly more bright and clear colours based on toxic heavy metals and fewer earth colours containing harmless iron and carbon compounds. These four painters may have been heavily exposed to mercury sulphide, cadmium sulphide, arsenic sulphide, lead, antimony, tin, cobalt, manganese, and chromium, the metals of the bright and clear colours, and exposure to these metals may be of importance in the development of inflammatory rheumatic diseases. Artists today are not so exposed, but heavy metal contamination in food and drinking water exists and experience from the occupational exposure of old masters is still relevant. PMID- 2897529 TI - Gene therapy in man. Recommendations of European Medical Research Councils. AB - 1. The purpose of gene therapy currently under consideration is the correction of genetic defects; attempts to enhance general human characteristics should not be contemplated. Only somatic cell gene therapy, resulting in non-heritable changes to particular body tissues, should be contemplated. Germline therapy, for introduction of heritable genetic modifications, is not acceptable. Further technical improvements in the expression of transferred genes in somatic cells will be necessary before successful gene therapy can be achieved even in animal models; in the meantime trials in man are not justified. 2. The most appropriate "candidate" genetic diseases for early investigation of treatment by gene therapy are single-gene disorders for which the affected gene and its regulation have been characterised. 3. In the near future, it is likely that success in the introduction of normal genes into human cells will be achieved through the use of disabled retrovirus vectors, although other techniques may advance rapidly. Much further work is required in the development of safe species-specific and tissue specific retrovirus vectors. The methods of gene introduction should not result in the spread of gene or vector to other tissues within the body or to people in contact with the patient. The possibility of a significant increase in the predisposition of the patient to cancer should be evaluated in considering the risks and benefits of the treatment. In addition, the expression and regulation of the gene inserted should be stable and sufficient to ensure a therapeutic effect. 4. General ethical considerations applicable to any new clinical treatment apply to human gene therapy and, in the first instance, will require assessment in individual cases. In the near future it is likely that such therapy will be clinically justified in particular patients with invariably fatal or life threatening diseases, provided informed consent is obtained and no alternative treatment is available. 5. A national body should consider all proposals for human gene therapy and ensure the application of agreed national guidelines. Early trials should be monitored by a central body. PMID- 2897530 TI - Embryos and Parkinson's disease. PMID- 2897531 TI - Legionnaires' disease: early lessons from 1988 London outbreak. PMID- 2897532 TI - Legionella: a case for culture. PMID- 2897533 TI - Self-poisoning in eating disorders. PMID- 2897534 TI - Intratracheal drugs. PMID- 2897535 TI - Chronic sinus node disease and coronary artery disease. PMID- 2897536 TI - Deaths during mountaineering at extreme altitude. PMID- 2897537 TI - Calcitonin for postmenopausal bone loss. PMID- 2897538 TI - Treatment of menopausal symptoms in breast cancer patients. PMID- 2897539 TI - Ectopic pregnancy after abortion. PMID- 2897540 TI - Erythraemia in renal transplant recipients treated with cyclosporin. PMID- 2897541 TI - Pneumonia in childhood. PMID- 2897543 TI - Cerebellar diaschisis. PMID- 2897542 TI - Gallstone pancreatitis from intestinal reflux. PMID- 2897544 TI - Influence of inhaled terbutaline on bronchial responsiveness. PMID- 2897545 TI - Successful stimulation and retrieval of oocytes in patient with Mayer-Rokitansky Kuster syndrome. PMID- 2897546 TI - 3-Oxo-delta 4 bile acids in liver disease. PMID- 2897547 TI - Autovaccination plus heat-inactivated autologous plasma in AIDS patients. PMID- 2897548 TI - Antibody-dependent enhancement of HIV infection. PMID- 2897549 TI - What is myalgic encephalomyelitis? PMID- 2897550 TI - Doppler uteroplacental waveforms. PMID- 2897552 TI - Pacemaker policy. PMID- 2897551 TI - IgG subclass deficiencies in chronic fatigue syndrome. PMID- 2897553 TI - Voluntary chemical castration of a mental patient. PMID- 2897554 TI - AIDS and life insurance. PMID- 2897555 TI - Testing for HIV infection. PMID- 2897556 TI - Controlled trial of hypnotherapy in relapse prevention of duodenal ulceration. AB - 30 patients with rapidly relapsing duodenal ulceration were studied to assess the possible benefit of hypnotherapy in relapse prevention. After the ulcer had healed on treatment with ranitidine, the drug was continued for a further 10 weeks during which time patients received either hypnotherapy or no hypnotherapy. The two randomly selected groups were comparable in terms of age, sex, smoking habits, and alcohol consumption. Follow-up of both groups of patients was continued for 12 months after the cessation of ranitidine. After 1 year, 8 (53%) of the hypnotherapy patients and 15 (100%) of the control subjects had relapsed. The results of this study suggest that hypnotherapy may be a useful therapeutic adjunct for some patients with chronic recurrent duodenal ulceration. PMID- 2897557 TI - Increased energy expenditure in young children with cystic fibrosis. AB - To investigate the role of energy expenditure in the altered energy balance in cystic fibrosis (CF), total energy expenditure (TEE) was measured by the doubly labelled water method in 9 clinically well CF infants (body weight 7.3-10.9 kg) without chronic lung disease. CF infants had 25% higher rates of energy expenditure when compared with data derived from measurements of TEE obtained by the same method in 16 healthy infants, matched for age and body weight. Mean TEE (SEM) for CF was 950 (38) kcal, vs 876 (72) kcal for controls matched for age and 758 (46) kcal for controls matched for weight. Although subclinical disease activity cannot be excluded as a determinant of the excess TEE, the possibility of an energy-requiring basic defect is suggested, because further analysis indicated that factors other than body weight, degree of underweight, presence of pancreatic insufficiency, or presence of lung disease were important. Increased TEE may contribute to undernutrition in CF, even in the absence of chronic lung disease. PMID- 2897558 TI - Acetylcholine sweatspot test for autonomic denervation. AB - A test for autonomic denervation based on the local sweat response to 0.1 ml 1% acetylcholine administered intradermally, which depends on an intact local sympathetic supply, is described. Diabetic autonomic neuropathy affects the longest fibres first and thus the test was applied to the feet. After painting a standard site on the dorsum of the foot with iodine and starch, acetylcholine was injected intradermally in the centre. The normal response, visible to the eye, is a uniform distribution of dark spots of iodine discolouration at the sites of sweat production. In diabetic autonomic neuropathy this pattern is lost to a varying degree. In a photographic image magnified x 10, the spots were counted in sixty 2.5 cm squares in a grid centred on the injection site. 50 normal volunteers aged 18-69 were tested. No effect of age or sex was found. Five or more squares with less than 6 spots was the definition of abnormal. 24 diabetic men who complained of impotence were investigated with the sweatspot test, a pupil test, and cardiovascular autonomic function tests. 13 had abnormal sweatspot tests with scores up to sixty squares with less than 6 spots. In keeping with the increased length of the sympathetic fibres to the feet compared with those to the iris, there was a 30% false-negative rate for the pupil test if the sweatspot test is taken as standard. Agreement between the cardiovascular tests and the sweatspot test was seen in only 17 patients. The sweatspot test appears to be a more sensitive indicator of autonomic neuropathy than the commonly used cardiovascular tests. PMID- 2897559 TI - Comparison of once daily ceftriaxone with gentamicin plus cefuroxime for treatment of serious bacterial infections. AB - To compare the efficacy of once daily monotherapy with that of standard combination antibiotic therapy for the initial management of patients suspected of serious bacterial infections, 105 patients were randomised to treatment with ceftriaxone alone (53 patients) or to a combination of cefuroxime and gentamicin (52 patients). There was no difference between the groups in proportions responding to therapy or proportions dying from infection, except when non evaluable patients were excluded from the group with definite bacterial infection, in which case response was better among those treated with ceftriaxone. The groups did not differ in number of side-effects, but therapy had to be discontinued because of treatment failure, an adverse effect, or death in 1 of 53 patients given ceftriaxone and in 11 of 34 given the combination. Use of ceftriaxone was 107.36 pounds ($182.51) cheaper per patient, and saved 40 minutes of nursing and drug administration time per patient per day. Thus 2 g ceftriaxone given once a day is at least as effective and costs less in time and money than gentamicin plus cefuroxime for the initial treatment of patients with serious systemic bacterial infections. PMID- 2897560 TI - Possible benefit of GR43175, a novel 5-HT1-like receptor agonist, for the acute treatment of severe migraine. AB - GR43175, a selective 5-HT1-like agonist, was given as an intravenous infusion in an open dose-ranging study to treat 46 attacks of severe migraine in 34 patients. The highest dose, 2 mg infused over 10 min in 24 severe attacks, resulted in rapid and complete relief of symptoms in 17 attacks (71%) and in improvement to a non-migrainous residual headache in 7 attacks. Treatment was well tolerated, the only adverse effects being transient feelings of heaviness and pressure, predominantly in the head. GR43175 may represent an important advance in the treatment of acute migraine. PMID- 2897561 TI - Congenital abnormalities in infants of diabetic mothers. PMID- 2897562 TI - Pulmonary hypertension: new information from necropsy-based studies. PMID- 2897563 TI - Klinefelter's syndrome. PMID- 2897564 TI - Cutaneous photosensitivity. PMID- 2897565 TI - Where to measure body temperature? PMID- 2897566 TI - Motoneuron disease and past poliomyelitis in England and Wales. AB - Past notification rates for poliomyelitis show a close geographical relation with current mortality from motoneuron disease in England and Wales. The increasing rate of poliomyelitis during the first half of this century and its predilection for affluent places and families were unique amongst infectious diseases. The unusual epidemiology of poliomyelitis is now being paralleled by motoneuron disease. These observations provide new evidence for a causal connection between the two conditions. PMID- 2897568 TI - Does maintenance therapy keep duodenal ulcers healed? AB - 34 patients were endoscopically reexamined once a month while receiving ranitidine 150 mg at night to sustain remission of a duodenal ulcer. The cumulative recurrence rate after 1 year of maintenance treatment was 48%. 71% of recurrences were painless when first detected. The monthly percentage probabilities for asymptomatic ulcers rehealing, remaining unchanged, and causing pain were 33%, 63%, and 4%, respectively. Because painless ulcers may reheal, the number of ulcer recurrences detected during maintenance trials depends on the frequency of endoscopic reexamination of symptomless patients. Endoscopic examination of symptomless patients every 6 months would have failed to detect nearly half of all recurrences in this study. Thus an accurate assessment of the true incidence of asymptomatic (and, therefore, total) recurrences requires frequent endoscopic re-examination of symptomless patients. The clinical value of maintenance treatment should be judged by prevention of symptoms and complications, since it is not possible--either practically or mathematically--to determine the true incidence of ulcer recurrence, and because asymptomatic recurrences are irrelevant, provided maintenance treatment is continued. PMID- 2897567 TI - Piezo-ceramic lithotripsy of gallbladder stones: initial experience in 38 patients. AB - The efficacy, safety, and side-effects of a piezo-ceramic system for extracorporeal shock-wave lithotripsy of gallbladder stones were assessed in the first 38 patients treated. Gallstone fragmentation was achieved in 34 patients; 25 required more than 1 treatment session (range 1-5). Extracorporeal shock-wave lithotripsy, conducted without sedation, analgesia, or anaesthesia, was well tolerated by all patients; no patient reported pain or discomfort either during or after the procedure. Side-effects were negligible: transient microscopic haematuria in 2 patients, transiently abnormal liver function tests in 1, and short-lived cutaneous petechiae in 4. Initial experience shows that lithotripsy with this system is effective, safe, and well tolerated. PMID- 2897569 TI - Lignocaine and ulcerative proctitis. PMID- 2897570 TI - Toxic shock syndrome after a minor surgical procedure. PMID- 2897572 TI - New life for the EEG. PMID- 2897571 TI - High incidence of anaphylactic reactions to cefaclor. PMID- 2897573 TI - Patch up the menopause. PMID- 2897574 TI - Placebos and limb ischaemia. PMID- 2897575 TI - Prone or supine for preterm babies? PMID- 2897576 TI - Aluminium phosphide: worse than Bhopal. PMID- 2897577 TI - Severity index of paraquat poisoning. PMID- 2897578 TI - False positive in prenatal diagnosis of cystic fibrosis. PMID- 2897579 TI - Treatment of osteosarcoma. PMID- 2897581 TI - Growth in children treated for acute lymphoblastic leukaemia. PMID- 2897580 TI - Leukaemia and growth hormone. PMID- 2897582 TI - Breast cancer screening. PMID- 2897583 TI - Factors affecting direct intraperitoneal insemination. PMID- 2897584 TI - Bubble ketoacidosis. PMID- 2897585 TI - Remedies for tropical diseases. PMID- 2897586 TI - Medicine and Israel's occupied territories. PMID- 2897587 TI - Disclosure of inactive drug ingredients. PMID- 2897589 TI - Doctors and torture. PMID- 2897588 TI - Europe's doctors after 1992. PMID- 2897590 TI - Efficacy of dexamethasone in benzodiazepine-resistant delirium tremens. PMID- 2897591 TI - Allergic bronchopulmonary mycosis. PMID- 2897592 TI - Endoscopist protection from biopsy valves. PMID- 2897594 TI - Drug information in Italy. PMID- 2897593 TI - Intoxication by benzodiazepines during pregnancy. PMID- 2897595 TI - Blood pressure increase after erythrocyte transfusion in end-stage renal disease. PMID- 2897596 TI - HIV-1 infection in Norwegian family before 1970. PMID- 2897598 TI - Breast-feeding and HIV infection. PMID- 2897597 TI - Adrenocortical lesions and HIV infection. PMID- 2897599 TI - Representation of the people? PMID- 2897600 TI - Prolongation of prothrombin time with ivermectin. PMID- 2897601 TI - Motoneuron disease as manifestation of lupin seed toxicity. PMID- 2897602 TI - Fetal "soap" addiction. PMID- 2897603 TI - Medicines Act passes crucial test. PMID- 2897604 TI - AIDS in Africa. PMID- 2897605 TI - [Laser-induced shockwave lithotripsy--in vitro trial and animal experiment studies]. AB - Laser induced shock wave lithotripsy is a new procedure to destroy gallstones. Stones of up to 500 mg are destroyed within 5 min. Severe reactions of the soft tissue cannot be observed in animal studies. No perforations, stenoses or thermic lesions after wound healing were observed. The development of an optomechanical transducer replacing the optical lens system at the end of the transmission guide allows its handling in flexible endoscopes. Clinical use is therefore possible from the technical aspect. PMID- 2897606 TI - [Thoracic dissecting aortic aneurysm. Contribution to the differential diagnosis of increased enzymes indicating cholestasis, fever and thoracic pain]. AB - A 68 years old female patient was admitted with thoracic pain and fever (40.0 degrees C). A coronary heart disease was known. The liver was enlarged, the cholestatic enzymes elevated without bilirubinaemia. In the blood culture gram negative bacilli was found. Our diagnosis: septic cholangitis, coronary ischemia. She was better by antibiotic therapy, the fever fell. Few days later she suddenly died. Autopsy demonstrated a serious arteriosclerosis of the aorta, an aneurysm on the aortic arc with chronic bleeding in the environmental tissue with inflammation and coronary arteriosclerosis. The liver was normal. PMID- 2897607 TI - A novel muscarinic receptor antagonist AF-DX 116 differentially blocks slow inhibitory and slow excitatory postsynaptic potentials in the rabbit sympathetic ganglia. AB - Muscarinic, slow postsynaptic potentials (s-epsp and s-ipsp) in the rabbit superior cervical ganglia were shown to be differentially depressed by a novel cardioselective M2-type antagonist AF-DX 116: it antagonized the s-ipsp with IC50 value of 1.5 X 10(-7) M, which is 16-fold more potent in depressing the s-ipsp than the s-epsp. A hyperpolarizing component in the biphasic potential changes induced by a muscarinic agonist, methacholine, was selectively eliminated by this antagonist. AF-DX 116 was thus shown to be an useful tool for discriminating the M2-type muscarinic responses from those of M1-type in the nervous system. PMID- 2897608 TI - Characterization of opioid receptors on isolated canine gallbladder smooth muscle cells. AB - Smooth muscle cells were isolated from the fundus of the canine gallbladder and examined for the presence of opioid receptors. The cells contracted in a concentration-dependent manner in response to three opioid peptides (Met enkephalin, dynorphin1-13 and Leu-enkephalin), which are known derivatives of opioid precursors present in myenteric neurons of the gut. The order of potency was Met-enkephalin greater than dynorphin1-13 greater than Leu-enkephalin. The contractile response to opioid agonists was selectively inhibited by opioid antagonists (naloxone and Mr2266) but not by muscarinic, CCK/gastrin or tachykinin antagonists. Equivalent responses to the three opioid peptides exhibited differential sensitivity to preferential antagonists of mu (naloxone) and kappa (Mr2266) opioid receptors consistent with the presence of the three main types of opioid receptors (mu, delta and kappa) on canine gallbladder muscle cells. PMID- 2897609 TI - Characterization of the putative anxiolytic SM-3997 recognition sites in rat brain. AB - In order to clarify the mechanism of action of the putative nonbenzodiazepine anxiolytic SM-3997 [3a alpha,4 beta,7 beta,7a alpha)-Hexahydro-2-(4-(4-(2 pyrimidinyl)-1- piperazinyl)-butyl)-4,7-methano-1H-isoindole-1,3 (2H)-dione dihydrogen citrate), in vitro binding studies with radiolabeled compound were performed. 3H-SM-3997 bound rapidly, reversibly and in a saturable manner with high affinity to rat brain hippocampal membranes (Kd = 9.4 nM, Bmax = 213 fmol/mg protein). This specific binding was displaced by 5-hydroxytryptamine (5-HT) and related compounds. Especially, 8-OH-DPAT, a 5-HT-1A selective agonist, bound with the highest affinity to these binding sites. 3H-SM-3997 binding, however, was not displaced by a variety of other neurotransmitters, neuropeptides and some other drugs. EDTA and physiological concentration of Na+ inhibited this specific binding, but several divalent cations, Mn2+, Ca2+ and Mg2+, enhanced this binding. GTP decreased the affinity of these binding sites for 3H-SM-3997 without changing the number of binding sites, but GMP and ATP did not influence 3H-SM 3997 binding. Furthermore, 3H-SM-3997 bound with marked regional selectivity to hippocampal membranes. These characteristics and the regional distribution of 3H SM-3997 binding sites were very similar to those of 3H-8-OH-DPAT binding sites (5 HT-1A receptors). Therefore, these results indicate that SM-3997 binds selectively and with high affinity to 5-HT-1A receptors in rat brain and may be an agonist. PMID- 2897610 TI - Polyunsaturated fatty acids in tissues of rats fed trielaidin and high or low levels of linolenic acid. AB - Male and female weanling rats that were born to dams fed a diet low in linolenic acid received diets of 15% lipids by weight containing 45% elaidic acid (as trielaidin) and 8.5% or 0.1% linolenic acid for 10 weeks. Four other groups, in which palmitic or oleic acid replaced elaidic acid in the diet, served as controls. The fatty acid profiles of several lipid classes were determined in adipose tissue, adrenals, testes, heart and brain. Elaidic acid was incorporated into tissue lipids in varying degrees, depending on the organ and on the lipid class. Feeding elaidic acid induced no changes in the polyunsaturated fatty acid (PUFA) profiles of testes lipids but resulted in definite modifications of the PUFA patterns of heart phosphatidylcholine (PC) and phosphatidylethanolamine (PE). In linolenic acid-deprived rats, arachidonic acid was decreased in PC and linoleic acid was increased in both PC and PE; 22:5n-6 was strongly depressed in both PC and PE. In linolenic acid-fed rats, 22:6n-3 was decreased in PC and PE. These changes, on the whole, were more evident in females, and some also were observed in adrenal cholesteryl esters but only slightly in brain phospholipids. The apparent inhibition of the biosynthesis of PUFA induced by dietary elaidic acid appeared to be complex and of greater intensity in the n-6 fatty acid series than in their n-3 homologues. PMID- 2897611 TI - Loss of genes on the long arm of chromosome 22 in human meningiomas. AB - It has been proposed that loss of genes at specific chromosomal loci leads to tumorigenesis in some human tumors. This type of oncogenesis was first demonstrated in retinoblastoma and Wilms' tumor. Recently, it has been reported that acoustic neuroma, ductal breast tumor, and renal cell carcinoma may be caused by the same mechanism. Cytogenetic studies demonstrated that some meningiomas have monosomy of chromosome 22. In addition, human meningiomas are often associated with bilateral acoustic neuroma in which specific loss of alleles on chromosome 22 has been demonstrated. Then, we compared constitutional and tumor genotypes from 14 cases of sporadic human meningiomas, using four polymorphic DNA probes on chromosome 22 (SIS, D22S1, D22S9, IGLC). Loss of constitutional heterozygosity was found in three of 11 informative cases. Two of the three meningiomas maintained constitutional heterozygosity at the IGLC locus and another one showed no loss of heterozygosity at IGLC or D22S9. These results suggest that loss of genes on chromosome 22 caused by either a partial deletion or a mitotic recombination at a locus distal to D22S9 plays an important role in tumorigenesis of the human meningioma. PMID- 2897613 TI - Renal ouabain inhibitable Na-K ATPase activity and myoinositol supplementation in experimental diabetes mellitus. AB - Alterations in ouabain inhibitable Na-K ATPase activity, polyol pathway activity, and myoinositol metabolism are part of a unifying hypothesis proposed to explain the pathogenesis of the chronic complications of diabetes mellitus. Direct measurements of renal ouabain inhibitable Na-K ATPase activity in animals with streptozotocin-induced diabetes show increased or decreased activity, depending on the nephron segment examined and the duration of diabetes. While myoinositol feeding corrects depressed Na-K ATPase activity in peripheral nerve of streptozotocin diabetic rats, the effect of myoinositol feeding on altered renal Na-K ATPase activity is unknown. To assess the effect of experimental diabetes on renal ouabain inhibitable Na-K ATPase activity and test the involvement of the polyol/inositol pathway, we assayed kidneys from normal, streptozotocin diabetic, and myoinositol-supplemented diabetic rats for renal ouabain-inhibitable Na-K ATPase, alkaline phosphatase, and tau-glutamyltranspeptidase (tau-GT) activity. Ouabain inhibitable Na-K ATPase activity, expressed per milligram of protein, is increased in the inner medulla of the diabetic kidney compared with normal and, expressed per microgram DNA, is increased in both the inner medulla and cortex. Myoinositol supplementation did not affect the increase in renal enzyme activity seen with streptozotocin diabetes. These observations suggest that the regulation of renal ouabain inhibitable Na-K ATPase activity, in streptozotocin diabetes, does not depend on supplemental myoinositol. These findings do not exclude the possibility that changes in polyol or myoinositol concentrations in a specific nephron segment may have pathogenetic significance for diabetic nephropathy. PMID- 2897612 TI - Nucleotide sequence analysis of a provirus derived from HTLV-1-associated myelopathy (HAM). AB - Human T-cell leukemia virus type 1 (HTLV-1) is known to be associated with adult T-cell leukemia (ATL). Recently, HTLV-1-associated myelopathy (HAM) was described as a neurological disease with which an etiological association of HTLV-1 is suspected. A provirus genome was cloned from a lymphoid cell line derived from the cerebrospinal fluid of a patient with HAM, in order to examine in detail the etiological virus associated with HAM. The nucleotide sequence of the long terminal repeat (LTR), protease, env and pX regions of the provirus shows over 97% homology with that of HTLV-1 derived from ATL. These results suggest that this provirus, derived from a patient with HAM, belongs to the same species as HTLV-1 derived from patients with ATL. PMID- 2897614 TI - Comparative effect of somatostatin-14 and somatostatin-28 on glucagon-induced glycogenolysis from the perfused rat liver. AB - The effect of somatostatin (SS)-14 and SS-28 on glycogenolysis was studied, using a rat liver perfusion technique. Livers from nonfasted rats were perfused with 5.5 mmol/L glucose or perfusate without the glucose addition. Glucagon-induced glucose output was lower in the presence of 5.5 mmol/L glucose than in glucose free perfusate at every concentration of glucagon. Under glucose free conditions, SS-14 given at five minutes prior to the glucagon addition reduced the glucagon induced glucose output dose-dependently. SS-14 given 15 minutes after glucagon addition also inhibited glucagon-induced glucose output significantly. However, various concentrations of SS-28 failed to affect glucose output. On the other hand, in the presence of 5.5 mmol/L glucose, neither SS-14 nor SS-28 affected glucagon-induced glucose output. It is suggested, therefore, that glycogenolysis induced by glucagon from the liver is reduced by SS-14, but not by SS-28, only under glucose free conditions. PMID- 2897616 TI - Hemagglutination by pilus antigen 987P of enterotoxigenic Escherichia coli. AB - The hemagglutination (HA) by pilus antigen 987P of an enterotoxigenic Escherichia coli strain 987 was examined using fresh and glutaraldehyde (GA)-fixed erythrocytes (RBC) of various animals. Only when GA-fixed RBC was employed, a strain 987 exhibited striking HA activities. This was also demonstrated by using latex heads sensitized with the 987P antigen. The 987P-specific antiserum inhibited HA of strain 987 and 987P sensitized latex beads against GA-fixed RBC. We concluded that HA of strain 987 against GA-fixed RBC was specifically associated with the presence of 987P pilus antigen but do not exclude a possibility that adhesin is distinct from pili antigen. PMID- 2897615 TI - Structure of the Saccharomyces cerevisiae URA4 gene encoding dihydroorotase. AB - The URA4 gene of Saccharomyces cerevisiae, coding for the third enzyme of the pyrimidine pathway, has been cloned through phenotypic complementation of a ura4 mutant of S. cerevisiae. Subcloning of an original 9 kb DNA fragment, carrying the yeast URA4 gene, allowed us to localize the gene on a 2 kb ClaI--BamHI fragment. The sequence of the URA4 structural gene and surrounding DNA was determined by the dideoxynucleotide chain termination method. The URA4 gene encodes a dihydroorotase subunit of calculated molecular weight 40,600. S1 nuclease mapping indicated that transcription of URA4 is initiated at four major start sites located at positions -41, -30, -22 and -18. A set of potentially significant sequences was identified in the 5' OH non-coding region of the gene. The deduced amino acid sequence of dihydroorotase was examined and compared with homologous amino acid sequences of Salmonella typhimurium, Escherichia coli and Drosophila melanogaster. S. cerevisiae dihydroorotase shows 40% homology with the S. typhimurium and E. coli enzymes and 23% homology with the D. melanogaster enzyme. A potential active site has been predicted for dihydroorotase from these comparisons. PMID- 2897617 TI - Role of pili in the pathogenesis of Pseudomonas aeruginosa burn infection. AB - The present study using three isogenic mutants (F+P-, F-P+, F-P-) of Pseudomonas aeruginosa indicates that the presence of pili enhances the virulence of the organisms in experimental P. aeruginosa burn infection of mice. The 50% lethal dose (LD50) value for burned mice inoculated with non-piliated (P-) mutant was at least ten times higher than those inoculated with piliated (P+) bacteria. Meanwhile the LD50 value for burned mice inoculated with non-flagellated (F-) mutant was at least 10(5) times higher than those inoculated with flagellated (F+) bacteria. At 24 hr after inoculation, the bacterial counts in burned skin of mice inoculated with P+ bacteria were ten times higher than those inoculated with P- bacteria; and at 48 hr the bacterial counts became a hundred times higher in the former mice than the latter. At 24 hr after inoculation, P+ bacteria were isolated from blood, liver (F+P+), lung (F+P+), and kidney, while P- bacteria were not present in these tissues. And at 48 hr after inoculation, P+ bacteria were isolated from all tissues, while P- bacteria were isolated from some sites only. These results suggested that pili and flagella each play an important role as virulence factors independently, and that pili-mediated enhancement of virulence of P. aeruginosa was attributed to pili-mediated enhanced colonization of the organisms at the burned skin surfaces. PMID- 2897618 TI - Characterization of a monoclonal antibody to guinea pig T cells that inhibits rosette formation of the cells with rabbit erythrocytes: similarity of the antigen to E-receptor on human T cells. AB - A monoclonal antibody, GPT-1, was prepared by fusion of the splenic cells of mice immunized with guinea pig thymocytes with a mouse myeloma cell line. GPT-1 completely inhibited spontaneous rosette formation of T cells with papain-treated rabbit erythrocytes. GPT-1 reacted with 90% of thymocytes, 70% of peripheral blood lymphocytes, and 45% of splenic lymphocytes, but not with B cells. These results indicate that GPT-1 has pan-T reactivity. The antibody specifically bound to a single polypeptide chain with a molecular size of 50-65 kD. The surface density of the antigen was higher on thymocytes than on peripheral T cells, suggesting that the antigen is a certain differentiation antigen on T cells. Phytohemagglutinin-activated T cells expressed more antigen molecules than resting T cells. In addition, GPT-1 suppressed the proliferation of T cells induced by the mitogen, indicating that GPT-1 recognizes a T cell-specific surface antigen which is associated with T cell activation. Based on these results, it was concluded that GPT-1 reacts with a guinea pig T cell surface antigen which is similar to the E-receptor protein on human T cells (CD2 molecule). PMID- 2897619 TI - DNA probes for presymptomatic diagnosis: keys to biological determinism? PMID- 2897620 TI - Prenatal and adult presymptomatic testing for Huntington's disease. AB - The discovery of a fragment of DNA that is linked closely to the Huntington's disease autosomal locus offers the opportunity for the presymptomatic diagnosis of this dominantly-inherited neurodegenerative disorder. Presymptomatic testing will present individuals and society with difficult choices and responsibilities. A pilot adult presymptomatic test programme is under way for SA families. Presymptomatic testing requires intensive counselling both before and after the test. A form of prenatal test, which is applicable to a significant proportion of couples with one partner at risk of Huntington's disease, is available also. As this form of prenatal test does not change the risk status of the parent, less extensive counselling is required and testing is available nationally through the SA programme. It is anticipated that other states will develop their own diagnostic programmes in the near future. This article explains the basis for the test, its accuracy and the importance of obtaining DNA from key individuals in pedigrees of Huntington's disease. PMID- 2897621 TI - Syrup of ipecac contamination. PMID- 2897622 TI - Stimulation of guanylate cyclase and RNA polymerase II activities in HeLa cells and fibroblasts by biotin. AB - HeLa cells cultured in a biotin-deficient medium showed reduced rates of protein synthesis, DNA synthesis and growth. Continuous synthesis is required for the increase in DNA synthesis observed upon addition of biotin to cells cultured in biotin-deficient medium. The addition of biotin to the biotin-deficient culture medium increased the activity of guanylate cyclase in both HeLa cells and fibroblasts. Both cell types cultured in biotin deficient medium showed reduced activity of RNA Polymerase II. The exogenous addition of biotin to the biotin deficient cell cultures also resulted in increased activity of RNA Polymerase II in HeLa cells and fibroblasts. The maximal response was observed in 4 hours. Significant increase in enzyme activity was observed at 10(-8) M biotin in the culture medium. The growth promoting effect of biotin seems to involve stimulations of cellular guanylate cyclase and RNA Polymerase II activity. PMID- 2897623 TI - [Interaction of acetyl-CoA carboxylase from the rat liver with analogs of activated carbon dioxide and ATP]. AB - The interaction of rat liver Ac-CoA-carboxylase with reactive and stable analogs of carbon dioxide and phosphoric acid mixed anhydrides--hypothetic intermediate of the enzyme reaction--has been studied. Carbamoylphosphate showed substrate properties, whereas phosphonacetic acid and beta-oxopropyl-alpha, alpha diphosphonate inhibited this enzyme (Ki 3.0 and 3.5 mM correspondingly). The analog of another possible intermediate in the reaction of ATP and carbon dioxide, Appp (CH2COOH) also inhibited Ac-CoA-carboxylase (Ki = 0.7 mM). PMID- 2897624 TI - Biased usage of certain Vk gene families by autoantibodies and their polymorphism in autoimmune mice. AB - Of 79 hybridomas derived from stimulated or unstimulated autoimmune disease prone mouse strains, secreting autoantibodies of various specificities more than 65% use V genes from five Vk families, namely, Vk1, Vk4, Vk8, Vk10 and Vk19. Restriction fragment length polymorphism (RFLP) analysis of genomic DNAs from autoimmune prone mouse strains, tight skin, NZB and SJL show marked differences in the polymorphism of the Vk1, Vk10 and Vk19 gene families. PMID- 2897625 TI - Transformation studies on human fibroblasts from familial polyposis coli patients and normal donors. AB - Transformation experiments have been carried out on human diploid fibroblasts derived from normal individuals and those from 2 groups with dominantly inherited cancer predisposition, familial polyposis coli (FPC), and multiple endocrine neoplasia, type 2 (MEN-2). Treatment with a single or multiple doses of the carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), resulted in limited anchorage-independent (AI) growth in both normal and FPC cultures; no permanent cell lines were produced but FPC cells showed increased proliferation with low doses of the carcinogen. Carcinogen treatment followed by application of the tumour promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA), for 38 weeks was insufficient to cause full transformation in cultures derived from normal people or MEN-2 patients although AI growth was induced in all 3 cell types. Three FPC cultures exhibited an extended life span over the solvent controls. Two of these are still actively dividing and have a clonal pseudodiploid karyotype. PMID- 2897626 TI - Theileria parva: genomic DNA studies reveal intra-specific sequence diversity. AB - Theileria parva parva piroplasm DNA was purified from 11 different infections of cattle with 6 different East African isolates of the parasite. Total DNA was also prepared from bovine lymphoblastoid cells infected with schizonts of one of the isolates. Two of the infections were with cloned parasites. The DNA was of high molecular weight and free from protein and RNA, but some of the samples contained a proportion of bovine DNA. The 6 samples least contaminated with bovine DNA had a mean 'melting' temperature (Tm) of 84 degrees C and a mean GC content of 31.3%. Reassociation kinetics gave an estimate of 1.2 x 10(7) base pairs for the genome of T. parva. Repetitive restriction fragments were cloned from two samples, separated from the recombinant vectors and used as probes to demonstrate RFLPs between isolates. Discrimination into five groups was achieved. Schizont and piroplasm DNAs from the same isolate gave identical RFLPs, and one of the cloned parasites appeared to be a sub-population selected from a mixed-infection field isolate. Comparison of RFLPs with monoclonal antibody profiles suggested that neither technique yet provides discrimination between all the isolates which may comprise a strain. The importance of DNA probes for studying the epidemiology of theileriosis and for control programs is discussed. PMID- 2897627 TI - Bedside diagnosis of systolic murmurs. AB - The diagnostic accuracy of bedside maneuvers in the evaluation of patients with systolic murmurs has not been assessed objectively. Therefore, we evaluated 50 patients with documented systolic murmurs and compared all standard bedside techniques. Murmurs originating within the right-sided chambers of the heart were best differentiated from all other murmurs by augmentation of their intensity with inspiration (100 percent sensitivity, 88 percent specificity) and diminution of their intensity with expiration (100 percent sensitivity, 88 percent specificity). The murmur of hypertrophic cardiomyopathy was distinguished from all other murmurs by an increase in intensity with the Valsalva maneuver (65 percent sensitivity, 96 percent specificity) and during squatting-to-standing action (95 percent sensitivity, 84 percent specificity), and by a decrease in intensity during standing-to-squatting action (95 percent sensitivity, 85 percent specificity), passive leg elevation (85 percent sensitivity, 91 percent specificity), and handgrip (85 percent sensitivity, 75 percent specificity). The murmurs of mitral regurgitation and ventricular septal defect had parallel responses to all maneuvers, but could be differentiated from other systolic murmurs by augmentation of their intensity with handgrip (68 percent sensitivity, 92 percent specificity) and during transient arterial occlusion (78 percent sensitivity, 100 percent specificity), and by a decrease in their intensity during the inhalation of amyl nitrite (80 percent sensitivity, 90 percent specificity). No single maneuver identified the murmur of aortic stenosis, but the diagnosis could be made by exclusion. Although no single maneuver is 100 percent accurate in diagnosing the cause of a systolic murmur, its origin can be determined accurately at the bedside by observation of the response to a combination of maneuvers. PMID- 2897628 TI - Hereditary defect of cobalamin metabolism (cblG mutation) presenting as a neurologic disorder in adulthood. PMID- 2897629 TI - Homologous plant and bacterial proteins chaperone oligomeric protein assembly. AB - An abundant chloroplast protein is implicated in the assembly of the oligomeric enzyme ribulose bisphosphate carboxylase-oxygenase, which catalyses photosynthetic CO2-fixation in higher plants. The product of the Escherichia coli groEL gene is essential for cell viability and is required for the assembly of bacteriophage capsids. Sequencing of the groEL gene and the complementary cDNA encoding the chloroplast protein has revealed that these proteins are evolutionary homologues which we term 'chaperonins'. Chaperonins comprise a class of molecular chaperones that are found in chloroplasts, mitochondria and prokaryotes. Assisted post-translational assembly of oligomeric protein structures is emerging as a general cellular phenomenon. PMID- 2897630 TI - Molecular cloning and expression of the major protein kinase C substrate of platelets. AB - In platelets, agonists that stimulate phosphoinositide turnover cause the rapid phosphorylation of a protein of apparent relative molecular mass (Mr) 40-47,000, called P47, by protein kinase C (PKC). Diverse identities have been ascribed to P47 including lipocortin, inositol 1,4,5-trisphosphate 5-phosphomonoesterase, pyruvate dehydrogenase alpha subunit and an actin regulatory protein. We have isolated human P47 clones by immunological screening of a lambda gt11 complementary DNA library from HL-60 cells, a human promyelocytic leukaemia cell line. P47 recombinants thus identified hybridized to a 3.0 kilobase (kb) messenger RNA in mature white blood cell lines; the same mRNA was induced in HL 60 cells during differentiation. A 1,050 base pair (bp) open reading frame that could encode a protein of Mr40,087 was confirmed by comparison with peptide sequences from platelet P47, and by expression of the putative recombinant P47 in E. coli and in vitro. The P47 sequence appears to have been conserved throughout vertebrate evolution, and is not similar to any other known sequence including human lipocortin and the alpha subunit of pyruvate dehydrogenase. The P47 protein contains a potential Ca2+-binding 'EF-hand' structure and a region that strongly resembles known PKC phosphorylation sites. PMID- 2897631 TI - Domain of Ultrabithorax expression in Drosophila visceral mesoderm from autoregulation and exclusion. AB - Domains of differential homeotic gene activity are formed at specific positions along the anteroposterior axis of the early Drosophila embryo. Homeotic genes are required continuously throughout development, so that homeotic gene activity has to be maintained independently of the positional information provided in the early embryo. In the ectoderm, the domains of homeotic gene activity partially overlap, but we have found that in the visceral mesoderm at least three of these genes are expressed in adjacent and mutually exclusive domains. It has been proposed that stable, sharply demarcated domains of this type could be established if a homeotic gene product stimulated its own expression locally and inhibited the expression of other homeotic genes, which Meinhardt has termed autocatalysis and mutual exclusion respectively. Furthermore, autocatalysis of this kind can in principle account for the maintenance of homeotic gene activity throughout development. We find that the unique domain of Ultrabithorax (Ubx) expression in the visceral mesoderm is dependent both on autocatalysis and on an exclusion mechanism: Ubx product is required for its own synthesis, whereas the product of the posteriorly adjacent gene abdominal-A represses Ubx expression. PMID- 2897632 TI - Primary structure and expression of a product from cut, a locus involved in specifying sensory organ identity in Drosophila. AB - In the absence of cut gene activity in Drosophila, external sensory organs are transformed into chordotonal organs. Here we show that the cut locus encodes a large protein containing a homoeodomain and is expressed in nuclei of cells in external sensory organs but not in cells within chordotonal organs. PMID- 2897633 TI - [Neuroleptics as anxiolytics and antidepressants]. PMID- 2897634 TI - [Stable angina pectoris; why has the prognosis changed so much?]. PMID- 2897635 TI - [Treatment of undescended testis with gonadorelin (LH-RH) via intranasal spray]. PMID- 2897636 TI - [Can orchidopexy as treatment of undescended testes be replaced by gonadorelin (LH-RH) via nasal spray?]. PMID- 2897637 TI - [Sharp decrease of the orchidopexy rate on Walcheren]. PMID- 2897638 TI - [Vaginismus, whose problem?]. PMID- 2897639 TI - VIP-sensitive adenylate cyclase, guanylate cyclase, muscarinic receptors, choline acetyltransferase and acetylcholinesterase, in brain tissue afflicted by Alzheimer's disease/senile dementia of the Alzheimer type. AB - Biochemical parameters were determined in autopsy material from several brain regions of thirteen patients with Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) (mean age 75 years) and from brains of ten age-matched controls (mean age 76 years). Choline acetyltransferase specific activity was significantly lower in the nucleus caudatus, putamen, left thalamus, hippocampus and the cortex from gyrus hippocampus and the temporal lobe in AD/SDAT, acetylcholinesterase specific activity was significantly lower in the hippocampus, parietal and left frontal lobe in AD/SDAT samples than in corresponding samples from aged-matched controls. A compensatory increase of muscarinic receptors was found in the nucleus caudatus and left frontal lobe samples in AD/SDAT. Guanylate cyclase activity was not significantly altered in AD/SDAT in the brain regions examined. The basal, non-stimulated activity of adenylate cyclase was significantly (p less than 0.05) elevated in hippocampus samples from AD/SDAT patients and the enzyme activity stimulated by the vasoactive intestinal polypeptide VIP (2 microM) or forskolin (10 microM) was also elevated in AD/SDAT although not significantly. PMID- 2897640 TI - Expression of Thy-1 antigen in reactive endoneurial capillaries of the rat following peripheral nerve damage. AB - Immunohistochemical staining of Thy-1 antigen was studied in rat peripheral nerves shortly after a complete crush lesion and after an epineural depot injection of lysophosphatidylcholine-palmitate (lysoPC). The Thy-1 antigen was expressed in endoneurial capillaries after 20-30 h and was visible previous to alterations in the axolemma or other signs of neural damage with the exception of endoneurial oedema formation. Thy-1 positive capillaries were restricted to the vicinity of degenerating nerve fibres in partially damaged nerves following epineural depot injection of lysoPC. It is therefore concluded that expression of the Thy-1 antigen in response to peripheral nerve damage in reactive endoneurial capillaries is an active process and not due to diffusion from degenerating axolemmata. Thy-1 staining could be used as a marker of reactive endoneurial capillaries in pathological conditions of peripheral nerves. PMID- 2897641 TI - Effect of cholinergic agonists and antagonists on rat hypothalamic corticotropin releasing hormone secretion in vitro. AB - Several lines of experimental evidence suggest that acetylcholine (ACh) is excitatory to the hypothalamic-pituitary-adrenal (HPA) axis. Since previous experiments have shown that ACh does not affect pituitary adrenocorticotropin secretion in vitro, we hypothesized that ACh stimulates the HPA axis by causing hypothalamic corticotropin-releasing hormone (CRH) secretion. We examined this hypothesis using an organ culture system that measures the ability of single rat hypothalami to secrete immunoreactive CRH (IR-rCRH) in vitro. ACh stimulated hypothalamic IR-rCRH secretion in a dose-dependent fashion, at concentrations ranging from 3.3 x 10(-10) to 10(-5) M. This effect was antagonized by the simultaneous presence of atropine and hexamethonium, a muscarinic and a nicotinic receptor antagonist, respectively (p less than 0.05). Further evidence for the cholinergic regulation of the CRH neuron was provided by the findings that both carbachol, a muscarinic receptor agonist, and nicotine, a nicotinic receptor agonist, stimulated IR-rCRH secretion in a dose-dependent fashion. These effects were antagonized by atropine and hexamethonium, respectively, suggesting that both muscarinic and nicotinic receptors are involved in the process. ACh stimulated hypothalamic IR-rCRH secretion in the presence of phentolamine, an alpha-adrenergic antagonist, and ritanserin, a serotonin2 receptor antagonist, suggesting that the cholinergic stimulation of CRH secretion is not mediated by alpha-adrenergic or serotonergic interneurons. We conclude that ACh stimulates hypothalamic CRH secretion via both muscarinic and nicotinic receptor mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897642 TI - Characterization of alpha-adrenoceptors in the nucleus reticularis gigantocellularis involved in the cardiovascular depressant effects of guanabenz in the rat. AB - The participation of alpha-adrenoceptors in the nucleus reticularis gigantocellularis in the hypotensive, negative inotropic and chronotropic effects induced by guanabenz, was examined in rats anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Pretreatment with alpha-adrenoceptor antagonists yohimbine (10 micrograms), phentolamine (2.5 micrograms) and phenoxybenzamine (20 micrograms), which were injected bilaterally into the nucleus reticularis gigantocellularis, significantly antagonized the cardiovascular suppressant effects normally produced by systemic administration of guanabenz (10 micrograms/kg, i.v.). Pretreatment with prazosin (0.25 microgram) did not affect the vasodepressive, but significantly attenuated the bradycardic actions of guanabenz. The general trend of "antagonization potency" shown by the alpha-adrenergic blockers, against the cardiovascular effects of guanabenz, was in the order: yohimbine greater than phentolamine greater than phenoxybenzamine greater than prazosin. It is concluded that while the alpha 2-adrenoceptors in the nucleus reticularis gigantocellularis are more critically involved in the antihypertensive actions of guanabenz, the possibility exists that alpha 1-adrenoceptors may also participate, in part. PMID- 2897643 TI - The pharmacological profile of Org 6906, a potential non-sedative antidepressant that combines monoamine uptake inhibition with alpha 2-adrenolytic activity. AB - (dl)-(5 alpha,8 alpha,9 alpha)-5,8,9,10-Tetrahydro-5,9- methanobenzocycloocten-8 amine hydrochloride (Org 6906) is a potential new antidepressant agent, with a neurochemical profile quite different from that of the classical tricyclic antidepressant drugs. The compound was found active in behavioural tests which are considered to be predictive for antidepressant activity, such as the muricidal test in the rat and the acquired immobility model. Neurochemical studies showed that Org 6906 was an inhibitor of the reuptake of monoamines both in vitro and ex-vivo without having appreciable anticholinergic, antihistaminergic or alpha 1-adrenolytic activity. The facilitatory effect on monoaminergic neurotransmission was confirmed by the reversal of hypothermia induced by reserpine. The drug Org 6906 appeared to have selective alpha 2 adrenolytic properties. It facilitated potassium-stimulated release of noradrenaline from slices of cortex, displaced [3H]rauwolscine and [3H]dihydroergocryptine from their binding sites but only weakly blocked alpha 1 adrenoceptors. The alpha 2-adrenolytic properties were also apparent in behavioural interaction models. The compound antagonized the sleep-inducing effects of clonidine in chicks and mice and it antagonized the mydriasis induced by clonidine in the rat. Finally, it was shown that the two enantiomers of Org 6906 contributed almost equally to the relevant neurochemical and behavioural properties. PMID- 2897644 TI - Effects of neuroleptic treatments on peripheral opioid secretion. AB - The effects of short- and long-term neuroleptic therapy on peripheral secretion of beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) were examined in 25 chronic schizophrenic patients. Haloperidol was given to 8 patients for 10 days (group A: 0.1 mg/kg b.w./day) and to another group of 8 patients for 30 days (group B: 10-18 mg/day). The other 9 patients were given a combination of haloperidol (6-30 mg/day) with either chlorpromazine (25-75 mg/day), clotiapine (40-60 mg/day), or fluphenazine decanoate (25-75 mg/month) for 14-18 months (group C). beta-EP and beta-LPH levels were assayed before and after each treatment. Haloperidol plasma levels were assayed in group B patients at the end of treatment. beta-EP mean basal levels were higher in patients than in controls; however, beta-LPH mean basal levels were higher only for group A patients. After treatment, the mean levels did not differ from those prior to therapy in groups A and B, while beta-LPH levels were significantly higher in group C. Level increases or decreases in single patients did not correlate with drug dose or duration of treatment, with baseline peptide levels or with the clinical effects of the various treatments. PMID- 2897645 TI - Co-localization of proenkephalin- and prodynorphin-derived opioid peptides in laminae IV/V spinal neurons revealed in arthritic rats. AB - By the use of highly selective antisera and an immunohistochemical technique the possible coexistence of proenkephalin- (PRO-ENK)- and prodynorphin (PRO-DYN) derived peptides was examined in 4- to 6-micron thick serial sections of the L4 L5 segments of the spinal cord of non-colchicine-treated polyarthritic rats. In control, non-colchicine treated animals, virtually no cell bodies stained for the PRO-ENK-derived peptides, heptapeptide (MRF) and octapeptide (MRGL), nor for the PRO-DYN-derived peptides, dynorphin A (DYN) and alpha-neoendorphin (NEO). In contrast, in polyarthritic rats, numerous large (15-30 micron) multipolar neurons could be visualized with each antiserum in laminae IV/V. Alternate staining of adjacent sections with either anti-MRF or anti-MRGL antisera, followed by either anti-DYN or anti-NEO antisera, revealed a clear coexistence of PRO-ENK and PRO DYN peptides. It was possible to demonstrate co-localization of all 4 opioids in a single cell. It appeared that all cells staining for PRO-ENK peptides in laminae IV/V also stained for PRO-DYN peptides. PMID- 2897646 TI - An excitatory amino acid projection from ventromedial hypothalamus to periaqueductal gray in the rat: autoradiographic and electrophysiological evidence. AB - The projection from ventromedial hypothalamus (VMH) to periaqueductal gray (PAG) has been implicated in various physiological processes in the rat, but the neurotransmitter mediating the excitatory response in PAG has not been identified. This pathway has been studied using a combination of anatomical and electrophysiological techniques. The retrograde labelling by D-[3H]aspartate in VMH, following injections into PAG, was particularly dense, suggesting that an excitatory amino acid may be the transmitter. This postulate is strengthened since VMH-evoked synaptic responses in PAG were reduced by microelectrophoretically administered antagonists of excitatory amino acids. Receptors of the N-methyl-D-aspartate and non-N-methyl-D-aspartate types appear to have a functional role in this projection. PMID- 2897647 TI - Inactivation of tyrosine hydroxylase in rat striatum by 1-methyl-4 phenylpyridinium ion (MPP+). AB - We report that 1-methyl-4-phenylpyridinium ion (MPP+), the active metabolite of 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), inactivated tyrosine hydroxylase (TH) when MPP+ was directly infused into the striatum. We examined both in vitro TH activity and TH content measured by an enzyme immunoassay in the rat striatum after MPP+ was administered by an in vivo brain microdialysis probe. MPP+ caused the inhibition of TH activity but did not influence TH content in the ipsilateral striatum. These results indicate that MPP+ may cause an acute inactivation of TH after continuous exposure at the high concentrations. PMID- 2897649 TI - Neurotransmitter receptors of the rolling mouse Nagoya: a quantitative autoradiographic study. AB - The distribution of neurotransmitter and neuromodulator receptors was studied in the brain of the rolling mouse Nagoya (RMN) and in controls, using in vitro receptor autoradiography. Quantitative autoradiography was used to map adenosine A1 (labeled with [3H]cyclohexyladenosine), GABAA [( 3H]muscimol), opiate [( 3H]naloxone), L-glutamate [( 3H]L-glutamate), benzodiazepine [( 3H]flunitrazepam), and muscarinic cholinergic [( 3H]quinuclidinyl benzilate) receptors. In the cerebellar cortex, GABAA and adenosine A1 binding sites were significantly reduced in the RMN, whereas other transmitter binding sites were not significantly altered. Adenosine A1 binding sites were also reduced in the cerebral cortex and caudate-putamen. Benzodiazepine binding was significantly decreased in the cerebral cortex and increased in the CA1 subfield of the hippocampus. These results suggest that neurochemical alterations in the caudate putamen as well as in the cerebellar cortex play important roles in the ataxia and motor dysfunction of the RMN. PMID- 2897648 TI - Dextrorphan and dextromethorphan, common antitussives, are antiepileptic and antagonize N-methyl-D-aspartate in brain slices. AB - The antitussive, dextromethorphan (DM), and its metabolite, dextrorphan (DX), were evaluated for antiepileptic properties in vitro. Interictal bursts and prolonged ictal epileptiform afterdischarges, induced by perfusion of guinea pig neocortical brain slices with Mg2+-free solution, were blocked by DX (1-250 microM) or DM (100 microM). Intracellular records showed that these agents blocked N-methyl-D-aspartate (NMDA)-induced depolarizations without altering intrinsic membrane properties. DX blocked NMDA but not quisqualate-evoked multi unit excitatory responses. DM is a widely available, orally effective drug with low toxicity in antitussive doses, which has antiepileptic and NMDA-antagonist properties in vitro. Its toxicity and effectiveness as an anticonvulsant should be expeditiously examined in clinical trials. PMID- 2897650 TI - The glutamate receptor subtype mediating parallel fibre-Purkinje cell transmission in rabbit cerebellar cortex. AB - Responses of Purkinje cells to parallel fibre stimulation and to ionophoretically applied glutamate agonists, L-glutamate, L-aspartate, quisqualate, kainate and N methyl-D-aspartate (NMDA), were extracellularly recorded in a superficial folium of the dorsal paraflocculus of high-decerebrate rabbits. NMDA caused an inhibition of simple spike discharge from Purkinje cells. 2-Amino-5 phosphonovalerate (APV), a selective NMDA receptor antagonist, effectively antagonized this inhibition. However, APV did not antagonize the excitation of Purkinje cells caused by quisqualate or parallel fibre stimulation. By contrast, both kynurenate and gamma-D-glutamylglycine (gamma-DGG) effectively antagonized the excitation of Purkinje cells by parallel fibre stimulation in a dose dependent manner. Both kynurenate and gamma-DGG also antagonized the excitation of Purkinje cells caused by quisqualate, L-glutamate, L-aspartate or kainate. However, the antagonism was more prominent to L-aspartate and kainate than to quisqualate and L-glutamate. Quisqualate response was antagonized to an extent comparable with the response to parallel fibre stimulation. These results indicate that the receptor for the neurotransmitter at parallel fibre-Purkinje cell synapses is of quisqualate-specific type. The present data are consistent with the evidence that L-glutamate is the endogenous transmitter at these synapses. PMID- 2897651 TI - Thyroid-stimulating immunoglobulin as a cause of recurrent intrauterine fetal death. AB - Hyperthyroidism is one of the numerous causes of infertility and recurrent abortion. Little mention has been made, however, of the specific role of thyroid stimulating immunoglobulin (TSIg) as a potential etiology, especially in the clinically euthyroid mother. This report describes a case of intrauterine fetal death in a euthyroid woman with TSIg. PMID- 2897652 TI - [New possibilities for the diagnosis and therapy of ischemic heart disease]. PMID- 2897653 TI - [Initial treatment of amputation injuries]. AB - Emergency treatment of an amputation injury is based on the correct assessment of the extent and functional loss of the amputated part. In addition to choosing the best treatment for the patient and amputated part, timely organization of transport and early contact with the replantation center are of utmost importance. We present the results of our experience based on replantations in 323 patients. PMID- 2897654 TI - Microfilaria density distribution in the human population and its infectivity index for the mosquito population. AB - A new method of computing the infectivity index of microfilariae (mf) for the mosquito population is proposed using the estimated mf density distribution in the human population. the observed density distribution is considered a compound of the Poisson and the gamma distributions. The former distribution describes the probability of a specimen containing a specified number of mf and the latter describes the density distribution of mf in the host population. The mf infectivity index is the probability that a blood meal will include at least 1 mf, conditional on the population-density distribution of mf as specified by the gamma distribution. Actual data indicate that this population-density-based infectivity index can be considerably different from the conventional index based on the survey-density distribution. The level of the carrier rate of mf in a survey is greatly influenced, apart from the sample variation, by the average volume of blood taken from each person. The rate computed on the estimated population-density distribution of mf is convertible to any base amount of blood. PMID- 2897655 TI - Use of restriction fragment length polymorphisms (RFLPs) to distinguish between nematodes of pathogenic significance. AB - The availability of restriction fragment length polymorphisms (RFLPs) would be useful for studying the extent of diversity among morphologically indistinguishable populations of filarial parasites. Such polymorphisms may be useful in correlating various physiological and clinical differences with parasite heterogeneity. In order to identify such RFLPs, we isolated DNA from microfilaria of 6 filarial species (Acanthocheilonema viteae, Brugia malayi, Brugia pahangi, Dirofilaria immitis, Litomosoides carinii and Setaria digitatum), digested the DNA with several restriction endonucleases, prepared Southern blots and probed with 32P-labelled DNA probes. The patterns of fragments generated using two restriction endonucleases, Mbo I and Taq I, in combination with two probes, rDNA from the free-living soil nematode Caenorhabditis elegans, and pBM103, an anonymous DNA probe from B. malayi, unequivocally distinguish between all 6 of the species. To ensure that the differences we observed between the species represent true interspecies variation rather than fortuitous individual variations we analysed DNA from several individual B. malayi and B. pahangi worms. The individual B. malayi worms demonstrated restriction profiles that were invariant, as did the individual B. pahangi worms, demonstrating that the differences we observed were true interspecies variations. PMID- 2897656 TI - The tissue distribution of the 3 alpha-fucosyl-N-acetyl lactosamine determinant recognized by the CD15 monoclonal antibodies CMRF-7 and 27. AB - Two monoclonal antibodies, CMRF-7 and 27, which react with cells of the granulocytic series, were obtained from hybridomas cloned from separate fusions. Biochemical studies indicate that both antibodies are of the CD15 group and react with the antigenic determinant 3 alpha-fucosyl-N-acetyl lactosamine (hapten X) expressed on some glycolipids and several different granulocyte glycoproteins with a wide range of molecular weights. The antigen was found on some promyelocytes and more differentiated granulocytes, including neutrophils and some eosinophils, but not basophils. Monocytes, lymphocytes, and erythrocytes were negative for CMRF-7 but neuraminidase treatment revealed "cryptic" sites on monocytes and some lymphoid cells. The antibody CMRF-7 reacted with the majority of acute myeloid leukemia blasts in the FAB categories M2-M5 but less frequently with M1 blasts and was positive with only 5/43 acute lymphoid leukemias. Immunoperoxidase staining of other normal human tissues indicates that this determinant is found on a range of epithelial cells in skin, the gastrointestinal tract and the genitourinary system. In addition some parts of the central nervous tissue and some endocrine organs stained with these antibodies. PMID- 2897657 TI - Cis-acting sequences affecting the length of the poly(A) head of vaccinia virus late transcripts. AB - Mutations in the sequences flanking the conserved and essential TAAAT motif of vaccinia late gene promoters (consensus: T/A T/A TAAAT G Pu Pu) affect the level of expression. Introduction of a pyrimidine in the purine stretch downstream of the TAAAT motif reduces the level of RNA synthesis. Mature transcripts from the wild-type 11K late promoter have a non-contiguous 5' poly(A) leader of approximately 35 A-residues (referred to as a poly(A) head). We show here by RNA sequencing, primer extension and subsequent m7G cap selection of cDNA/RNA hybrids that the mutations affect the length of the poly(A) head but not the location of the junction between the poly(A) leader and sequences encoded in the genome. These results are consistent with a slippage mechanism underlying the process of 5' poly(A) addition, but are not in agreement with a splicing event. PMID- 2897659 TI - Isolation and mapping of a polymorphic DNA sequence (pMCT128.2) on chromosome 8 [D8S39]. PMID- 2897658 TI - Regulation of in vitro translation by double-stranded RNA in mammalian cell mRNA preparations. AB - Polyadenylated mRNA has been purified from a variety of human and mouse cell sources. These preparations are actively translated in the wheat germ cell-free system but have only poor ability to stimulate the nuclease-treated reticulocyte lysate. The translation of endogenous and exogenous globin mRNA is strongly inhibited by the poly(A)+ RNA preparations in reticulocyte lysates. Both polysomal and non-polysomal RNA have similar effects but poly(A)+ RNA is almost 2000-fold more inhibitory than poly(A)-RNA on a weight basis. The inhibition is abolished in the presence a high concentration of poly(I).poly(C). Analysis of endogenous eIF-2 in the lysate reveals that the subunit becomes extensively phosphorylated in the presence of the inhibitory poly(A)+ RNA. Prolonged incubation of lysate with poly(A)+ RNA also causes some nucleolytic degradation of polysomal globin mRNA. These characteristics suggest that some eukaryotic cell mRNAs contain regions of double-stranded structure which are sufficiently extensive to activate translational control mechanisms in the reticulocyte lysate. PMID- 2897660 TI - Isolation and mapping of a polymorphic DNA sequence (pRMU7.4) on chromosome 7p [D7S370]. PMID- 2897661 TI - Isolation and mapping of a polymorphic DNA sequence (pYNM18.1) on chromosome 15 [D15S35]. PMID- 2897662 TI - Isolation and mapping of a polymorphic DNA sequence (pTHH37) on chromosome 14 [D14S16]. PMID- 2897663 TI - Isolation and mapping of a polymorphic DNA sequence (cMCOC46) on chromosome 13 [D13S54]. PMID- 2897664 TI - Isolation and mapping of a polymorphic DNA sequence (pYNA15.2) on chromosome 15 [D15S36]. PMID- 2897665 TI - Isolation and mapping of a polymorphic DNA sequence (pCMM1.2) on chromosome 12q [D12S15]. PMID- 2897666 TI - Isolation and mapping of a polymorphic DNA sequence (cYNA12) on chromosome 13 [D13S53]. PMID- 2897667 TI - Isolation and mapping of a polymorphic DNA sequence (pTHH59) on chromosome 17q [D17S4]. PMID- 2897668 TI - Apa I and Sst I RFLPs at the insulin-like growth factor II (IGF2) locus on chromosome 11. PMID- 2897669 TI - Magnesium-dependence of in vitro translation programmed by gene-specific mRNAs. PMID- 2897670 TI - Human TaqI RFLP recognized by neurofilament gene probes. PMID- 2897671 TI - RFLP for TaqI at the human neurofilament (NF-L) gene locus. PMID- 2897672 TI - Isolation and mapping of a polymorphic DNA sequence (pYNZ32) on chromosome 4p [D4S125]. PMID- 2897673 TI - Isolation and mapping of a polymorphic DNA sequence (pTB10.171) on chromosome 10 [D10S19]. PMID- 2897674 TI - Isolation and mapping of a polymorphic DNA sequence (pHHH163) on chromosome 18 [D18S21]. PMID- 2897675 TI - Isolation and mapping of a polymorphic DNA sequence (pCMM17.4) on chromosome 10 [D10S23]. PMID- 2897676 TI - Isolation and mapping of a polymorphic DNA sequence (pCMI37) on chromosome 7 [D7S368]. PMID- 2897677 TI - RFLP of the human c-fes proto-oncogene. PMID- 2897678 TI - Gastric secretion and gastrin under progressive doses of somatostatin-14 and -28 administered intraperitoneally to the rat. AB - The actions of progressive doses of intraperitoneally (IP) administered somatostatin-14 (SS-14) and -28 (SS-28) on gastric secretion (acid, pepsin) and mucosal blood flow (MBF) were studied in conscious gastric fistula rats both under basal conditions and under additional administration of pentagastrin. Also, somatostatin-like immunoreactivity was measured in aortal blood in all groups as well as aortal gastrin levels under basal conditions. IP infusion of equimolar doses of SS-14 and SS-28 resulted in an equal and dose-dependent inhibition of basal as well as pentagastrin-stimulated gastric acid secretion. MBF was reduced by either peptide both in the basal and pentagastrin experiments. Under basal conditions pepsin secretion was significantly increased by infusion of SS-14 at the higher doses, by infusion of SS-28 only at the intermediate dose (3.1 nmole kg-1.hr-1). In the pentagastrin experiments, low and intermediate doses of SS-14 tended to lower pepsin outputs but the highest dose of SS-14 stimulated pepsin secretion, whereas SS-28 had no effect on pepsin. Administration of SS-28 inhibited gastrin only at the highest dose (12.3 nmole kg-1.hr-1), and SS-14 had no influence at all on gastrin. After IP infusion of both peptides, plasma SLI rose dose-dependently under basal and stimulated conditions. Gel chromatography indicated an in-vivo conversion of SS-28 to SS-14 or intermediate fragments. It is concluded that SS-14 and SS-28 delivered by IP infusion, inhibit basal and stimulated gastric acid equally in the rat without suppressing gastrin. The mechanism underlying SS-mediated pepsin stimulation is unknown. PMID- 2897680 TI - [The role of neurotransmitters and neuropeptides in the regulation of thyrotropin secretion in rats]. PMID- 2897679 TI - [The factors and mechanisms regulating the number and function of peripheral receptors of the adrenergic system]. PMID- 2897681 TI - Pain management in terminally ill patients. How the primary care physician can help. PMID- 2897682 TI - Amebiasis. The ancient scourge is still with us. AB - Amebiasis is usually contracted in geographic areas where sanitation is poor, but outbreaks can still occur anywhere that drinking water becomes contaminated with sewage. In the majority of persons infected with the parasite, colonization of the intestine is asymptomatic. In others, symptoms of gastrointestinal distress can appear within a week. In rare cases, extra-intestinal amebiasis can cause abscesses in the liver or elsewhere. Many questions about the disease course in different patients remain to be answered. Diagnosis can be made through symptom identification; findings of right-upper-quadrant tenderness, leukocytosis, and an elevated level of alkaline phosphatase; and testing the feces for trophozoites or cysts. Clinicians disagree on whether asymptomatic persons need to be treated, but anyone who is capable of transmitting the disease should be advised of how to avoid exposing others to it. PMID- 2897683 TI - Clostridium difficile, sulphasalazine, and ulcerative colitis. AB - Clostridium difficile has been implicated in the relapse of ulcerative colitis. Controversy exists over this role and its relationship to sulphasalazine exposure. Sixty two of 77 patients with a documented relapse of ulcerative colitis were investigated for the presence of Clostridium difficile, or its toxin, prior to hospitalization. There was a low incidence of detection which was related to antibiotic exposure (2/62). Sampling during the treatment period showed that the occurrence of Clostridium difficile in the stool was related to antibiotic treatment (2/66). Fifty six percent of patients were taking sulphasalazine, none of whom became culture or toxin positive. This study demonstrates that Clostridium difficile is not related to relapse of ulcerative colitis and is not secondarily acquired during relapse unless the patient is exposed to antibiotics. Sulphasalazine does not predispose to acquisition of Clostridium difficile. There is no role for routine screening or treatment of Clostridium difficile in ulcerative colitis. PMID- 2897684 TI - Microvillar enzyme assays in amniotic fluid and fetal tissues at different stages of development. AB - A systematic study of microvillar enzyme activities in the amniotic fluid in correlation with their values in different fetal tissues during development has been undertaken. Microvillar enzymes appeared in the amniotic fluid at the time of disappearance of the anal membrane, 12-13 weeks, and declined from the 18th week until the 24th week. The study of fetal tissues and fluids has shown that gamma-glutamyltranspeptidase is mainly of liver origin. The significant decrease of the activities of these amniotic fluid enzymes has been the basis of prenatal diagnosis of cystic fibrosis. These assays may be useful for the diagnosis of certain digestive tract abnormalities at later stages of pregnancy. PMID- 2897685 TI - First trimester diagnosis of methylmalonic aciduria. AB - We have studied methylmalonyl CoA mutase activity in control chorionic villi to establish the potential use of assays performed directly on this tissue for prenatal diagnosis of methylmalonic aciduria. We report the detection of a fetus affected with the apo-mutase deficient form of this condition at 9 weeks' gestation. Methylmalonyl CoA mutase was markedly deficient in chorionic villi, approximately 2.5 per cent of the mean control value. However, incorporation of label from [14C]-propionate into protein was 10 and 40 per cent of the mean control value, respectively, in two portions of the same biopsy, highlighting potential problems in the use of this indirect assay. Normal results were obtained in chorionic villus samples from four other pregnancies 'at risk' for methylmalonic aciduria which were subsequently shown to be unaffected with this condition. The diagnosis in the affected pregnancy was confirmed by demonstration of a marked deficiency of methylmalonyl CoA mutase activity in villi obtained at termination and in cultured fetal fibroblasts. Reduced incorporation of [14C] propionate label into protein was also found in these tissues. PMID- 2897686 TI - The preparation of poly(A)+mRNA from the hagfish slime gland. AB - The isolation of translatable poly(A)+mRNA from the slime glands of the Pacific hagfish, Eptatretus stouti, is not possible by the commonly used procedures because of the viscous slime that is formed when the contents of the glands are hydrated. This paper reports on a procedure developed to overcome this problem. Briefly, the tissue was powdered in liquid nitrogen, mixed with sodium lauroylsarcosine and proteinase K and lyophilized. The lyophilized powder was then mixed with 0.3 mm diameter glass beads, thoroughly ground and wetted with buffer and digested at 37 degrees C. The RNA from the digest was recovered by ultracentrifugation through a CsCl cushion. Further purification of the RNA was accomplished by the usual methods with slight modifications. PMID- 2897687 TI - Long-acting somatostatin (SMS 201-995) in the management of Zollinger-Ellison syndrome: evidence for sustained efficacy. AB - Five patients with Zollinger-Ellison syndrome (ZES) have been treated during 9-12 months with long-acting somatostatin (SMS 201-995). Basal acid output presented a sustained decrease in 4 of 5 cases, below 10 mmol/h in three patients, allowing ranitidine discontinuation. No escape phenomenon was observed. Maximal acid secretion progressively decreased, suggesting an SMS antitrophic effect. Serum gastrin level was affected in a greater extent, showing a mean 87% decrease throughout the treatment period. Thus three patients kept normal serum gastrin levels in the long-term; one escaped to SMS after 9 months. Associated endocrine neoplasia were poorly influenced by SMS. No convincing evidence of tumor size variation was noted. Tolerance of SMS was excellent in the five patients. SMS' antitrophic and antigastrin properties could be of great interest in long-term management of ZES. PMID- 2897688 TI - Purification of human pancreatic gamma-glutamyltranspeptidase by lectin affinity chromatography. AB - Two types of pancreatic gamma-glutamyltranspeptidase (GGTP) (EC 2.3.2.2), sialic acid poor and sialic acid rich, were purified by the following: anion-exchange chromatography, wheat germ agglutinin (WGA)-Sepharose chromatography, gel filtration chromatography, phenyl-Superose chromatography, and hydroxylapatite chromatography. Among these, WGA-Sepharose chromatography helped to increase the specific activity of the GGTPs by approximately 20-30-fold in one effort. On dodecyl sulfate polyacrylamide gel electrophoresis, the two pancreatic GGTPs had different molecular weights. Sialic acid-rich GGTP had two subunits of Mr 67,000 and 27,000; however, the sialic acid-poor type had two subunits of Mr 72,000 and 29,000. The pI value of the sialic acid-poor GGTP was 5.9, and that of the sialic acid-rich GGTP 3.6. PMID- 2897689 TI - Distinct P-glycoprotein precursors are overproduced in independently isolated drug-resistant cell lines. AB - A family of P-glycoproteins are overproduced in multidrug-resistant cells derived from the murine macrophage-like line J774.2. To determine whether individual family members are overproduced in response to different drugs, the P glycoprotein precursors in several independently isolated cell lines, which were selected for resistance to vinblastine or taxol, were compared. Individual cell lines selected with vinblastine overproduced P-glycoprotein precursors of either 120 or 125 kDa. Taxol-selected cell lines overproduced either the 125-kDa precursor or both precursors simultaneously. Two similar but distinct peptide maps for the mature P-glycoproteins were observed. These maps corresponded to each precursor regardless of the drug used for selection. One vinblastine resistant cell line switched from the 125- to the 120-kDa precursor when grown in increasing concentrations of drug. This change coincided with the overexpression of a distinct subset of mRNA species that code for P-glycoprotein. It is concluded that precursor expression is not drug-specific. These data suggest that individual overproduced P-glycoprotein family members are translated as distinct polypeptides. The results may help to explain the diversity in the multidrug resistant phenotype. PMID- 2897690 TI - Suppression of the Escherichia coli ssb-1 mutation by an allele of groEL. AB - A series of spontaneous suppressors to the temperature-sensitive phenotype of the single-stranded DNA-binding protein mutation ssb-1 were isolated. A genomic library of EcoRI fragments from one of these suppressor strains was prepared by using pBR325 as the cloning vector. A 10.0-kilobase class of inserts was identified as carrying the ssb-1 gene itself. A second class of 8.3-kilobase inserts was shown to contain the groE region by (i) restriction analysis, (ii) Southern hybridization of the 8.3-kilobase insert to groE+ DNA, and (iii) identification of the gene products by similar migration on polyacrylamide gels. Subcloning demonstrated that an intact mutant groEL gene was necessary for suppression and that plasmids carrying the 8.3-kilobase insert could suppress mutants carrying groES- but not groEL- genes for phage lambda growth. The suppressor, designated as groEL411, was specific for the ssb-1 allele. In ssb-1 groEL411 cells, DNA synthesis stopped after a shift to 42.5 degrees C but rapidly recovered within minutes. The data suggest a direct interaction between the single-stranded DNA-binding protein and GroEL proteins in DNA replication. PMID- 2897691 TI - Positive regulation of pertussis toxin expression. AB - Although the genus Bordetella contains several closely related species, pertussis toxin (PT) is produced only by phase I Bordetella pertussis. In this work we have studied the regulation of expression of the PT operon and investigated why PT is produced by phase I and not by phase III B. pertussis despite the presence of the PT genes. We have constructed a vector for Bordetella species that contains the PT promoter fused to the coding region of the chloramphenicol acetyltransferase (CAT) gene, and we have used it to identify the regulatory elements involved in the transcription of the PT operon. Efficient transcription of these genes requires at least two features: (i) the 170-base-pair DNA sequence upstream from the start site of transcription and (ii) a trans-activating factor encoded by the vir locus. Bordetella parapertussis and Bordetella bronchiseptica, although endowed with a functional trans-activating system, do not produce PT because of mutations within their PT promoter regions. In contrast, phase III Bordetella species do not show any trans activity. PMID- 2897692 TI - Insulin growth factors regulate the mitotic cycle in cultured rat sympathetic neuroblasts. AB - While neuronal mitosis is uniquely restricted to early development, the underlying regulation remains to be defined. We have now developed a dissociated, embryonic sympathetic neuron culture system that uses fully defined medium in which cells enter the mitotic cycle. The cultured cells expressed two neuronal traits, tyrosine hydroxylase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] and the neuron-specific 160-kDa neurofilament subunit protein, but were devoid of glial fibrillary acidic protein, a marker for non-myelin-forming Schwann cells in ganglia. Approximately one-third of the tyrosine hydroxylase-positive cells synthesized DNA in culture, specifically incorporating [3H]thymidine into their nuclei. We used this system to define factors regulating the mitotic cycle in sympathetic neuroblasts. Members of the insulin family of growth factors, including insulin and insulin like growth factors I and II, regulated DNA synthesis in the presumptive neuroblasts. Insulin more than doubled the proportion of tyrosine hydroxylase positive cells entering the mitotic cycle, as indicated by autoradiography of [3H]thymidine incorporation into nuclei. Scintillation spectrometry was an even more sensitive index of DNA synthesis, revealing a 4-fold insulin stimulation with an ED50 of 100 ng/ml. Insulin-like growth factor I was 100-fold more potent than insulin, whereas insulin-like growth factor II was less potent, suggesting that insulin growth factor type I receptors mediated the mitogenic responses. In contrast, the trophic protein nerve growth factor exhibited no mitogenic effect, suggesting that the mitogenic action of insulin growth factors is highly specific. Our observations are discussed in the context of the detection of insulin growth factors and receptors in the developing brain. PMID- 2897693 TI - Neurotransmitter release is blocked intracellularly by botulinum neurotoxin, and this requires uptake of both toxin polypeptides by a process mediated by the larger chain. AB - Botulinum neurotoxins (types A and B), which are microbial proteins consisting of two disulfide-linked chains, inhibit specifically and with high potency the release of acetylcholine from peripheral nerve terminals. As a prerequisite for a long-term development of effective treatments for botulism, the internalization and inhibitory action of the toxin and its constituent chains were examined by electrophysiological methods at identified synapses in Aplysia preparations that allow both intracellular and bath application of the neurotoxins. Intracellular recordings from cholinergic cells of the buccal ganglion demonstrated that extra- or intracellular application of low doses of botulinum neurotoxin results in a specific blockade of evoked transmitter release, without changing the quantal size; an intraneuronal site of action has thus been established. In contrast, release from noncholinergic neurons of cerebral ganglion was prevented by the neurotoxin only after injection into the cell. Purified preparations of the individual renatured chains, shown to be nontoxic in a mouse bioassay, failed to affect acetylcholine release when applied extra- or intracellularly. However, inhibition of release was observed after intracellular administration of both chains or when the light chain was injected and the heavy chain was bath-applied. These findings show that both chains are required on the cytosolic side of the neuronal plasma membrane for expression of toxicity and that the cholinergic specificity of the neurotoxin is attributable to its heavy chain, which mediates targeting and subsequent neuronal uptake. PMID- 2897694 TI - Effects of dietary nonspecific nitrogen on [14C]glutamate and [14C]proline incorporation into bone proteins in chicks. AB - The incorporation of [14C]glutamic acid into EDTA-soluble and -insoluble calvaria protein in vitro and [14C]proline into EDTA-insoluble femur protein in vivo was determined in chicks fed inadequate and adequate levels of nonspecific nitrogen (glutamic acid). In each instance, the amount of amino acid incorporated into bone protein was reduced by the low level of nonspecific nitrogen. It was concluded that the high incidence of leg abnormalities observed in chicks fed purified diets containing adequate levels of indispensable amino acids but lacking in total nitrogen might be associated with an inability to form bone matrix protein. PMID- 2897695 TI - Use of analogs of LH-RH and somatostatin for the treatment of hormone dependent cancers. PMID- 2897696 TI - The role of the multichain IL-2 receptor complex in the control of normal and malignant T-cell proliferation. AB - Antigen-induced activation of resting T cells induces the synthesis of interleukin-2 (IL-2), as well as the expression of specific cell surface receptors for this lymphokine. There are at least two forms of the cellular receptors for IL-2, one with a very high affinity and the other with a lower affinity. We have identified two IL-2 binding peptides, a 55-kd peptide reactive with the anti-Tac monoclonal antibody and a 75-kd non-Tac IL-2 binding peptide. Cell lines bearing either the p55, Tac, or the p75 peptide alone manifested low affinity IL-2 binding, whereas cell lines bearing both peptides manifested both high- and low-affinity receptors. Fusion of cell membranes from low-affinity IL-2 binding cells bearing the Tac peptide alone with membranes from a cell line bearing the p75 peptide alone generated hybrid membranes bearing high-affinity receptors. We propose a multichain model for the high-affinity IL-2 receptor in which both the p55 Tac and the p75 IL-2 binding peptides are associated in a receptor complex. The p75 peptide is the receptor for IL-2 on large granular lymphocytes and is sufficient for the IL-2 activation of these cells. In contrast to resting T cells, human T-cell lymphotropic virus I-associated adult T-cell leukemia cells constitutively express large numbers of IL-2 receptors. Because IL 2 receptors are present on the malignant T cells but not on normal resting cells, clinical trials have been initiated in which patients with adult T-cell leukemia are being treated with either unmodified or toxin-conjugated forms of anti-Tac monoclonal antibody directed toward this growth factor receptor. PMID- 2897697 TI - Effect of ethylketocyclazocine on acetylcholine release in guinea-pig brain slices. AB - The effect of ethylketocyclazocine (EKC) on 3H-Choline (Ch) efflux and on endogenous acetylcholine (ACh) release from guinea-pig brain slices was studied. The drug inhibited the 3H-Ch efflux at a low concentration (0.1 mumol/l) in thalamus slices, while only at high concentrations (30-100 mumol/l) did EKC induce deep inhibition in the caudate nucleus and slight reduction in the cerebral cortex. Dynorphin (1-13) and morphine (Mo) inhibited the ACh release from thalamus slices as well. Naloxone (Nx) was more effective in antagonizing Mo than EKC. The experiments carried out with the endogenous ACh bioassay technique confirmed the above results. Mr 2266 and Mr 1452, both proposed as preferential k antagonists, per se enhanced 3H-Ch efflux from thalamus slices, while the dextrorotatory isomer Mr 1453, devoid of opioid properties, did not share such action. The role of k-opioid receptors in cholinergic system modulation in the guinea-pig brain is discussed. PMID- 2897698 TI - Development of gamma-glutamyl transpeptidase activity in primary cultures of neurones and glial cells derived from the cerebral hemispheres of chick embryos. AB - The development of gamma-glutamyl transpeptidase (GGT) activity in neurones and glial cells was studied in primary cell cultures derived from the cerebral hemispheres of chick embryos. GGT activity was found in both basic types of nervous tissue cells. It was always higher in glial cell cultures, where it was up to 2.3-fold the values in neurone-enriched cultures. If the culture medium contained foetal calf serum, the GGT activity of both types of nerve cells was higher than in the presence of inactivated calf serum. Comparison with the in vivo situation showed that the level of GGT activity in nerve cell cultures was significantly lower. Between the seventh day of embryogenesis and the third day of postnatal development of the nerve cells, there were marked differences between the GGT activity of cells maintained under in vitro conditions and cells of the same age in brain tissue homogenate. GGT activity in cerebral hemisphere homogenates from a 17-day-old embryos amounted to 4-fold the activity in a primary glial cell culture and to 16-fold the value in a neurone-enriched culture from hemispheres at the same stage of development. PMID- 2897699 TI - Central mechanisms underlying the neural and neuroendocrine determinants of maternal behaviour. AB - The neuroendocrine and neurochemical events which occur in the brain in the context of maternal behaviour fall into two main categories: 1) Those which simultaneously address wide areas of the brain and lack any specific "coding" for maternal behaviour but are nevertheless essential for it to occur. The steroid hormones and rostrally projecting catecholamine systems fall into this category. The steroid hormones may be viewed as primers, but not just for maternal behaviour, while the amines, specifically noradrenaline, act to synchronise a variety of neural systems associated with maternal behaviour. These include the activation of neuroendocrine mechanisms important for the peripheral changes associated with maternal behaviour, an interaction with the oxytocin and beta endorphin peptidergic systems which are the specific addressing systems, and enhancement of sensory signals and learning contingent upon parturition. Indeed, parturition is the physiological event which activates the noradrenergic system in the context of maternal behaviour. 2) Those which address restricted areas of the brain and may be viewed as specific to maternal behaviour. Their action is dependent on estrogen priming and the noradrenergic synchronisation of other neural events in order for complete maternal behaviour to ensue. The oxytocinergic and beta-endorphin peptidergic systems fall into this category, promoting maternal behaviour and the neural reinforcement associated with this. In order to ensure specificity, these peptidergic systems may be inhibitory to potentially competing behaviours such as sexual behaviour and the reproductive neuroendocrine response associated with it. Although not discussed in this review, the nigrostriatal dopamine projection may be considered both specific, in that it relates only to motor events, and non-specific, in that this relationship exists in all behavioural contexts. Finally, as maternal behaviour progresses, other parts of the brain are called upon to coordinate the different behaviours that become associated with maternalism and ensure protection and feeding of the offspring. The suckling stimulus appears to be important for activating these neural systems by way of the peripeduncular nucleus. PMID- 2897700 TI - Neural basis of maternal behavior in the rat. AB - This article presents a review of the neural and neurochemical regulation of maternal behavior in the rat, emphasizing the role of the medial preoptic area (MPOA) and its neural connections in this regulation. Evidence for the role of the MPOA includes the following and will be discussed: (1) Axon-sparing lesions of the MPOA disrupt maternal behavior, indicating the involvement of MPOA neurons rather than fibers of passage. (2) Estradiol acts on the MPOA to facilitate maternal behavior. (3) An MPOA-to-lateral preoptic area-to-ventral tegmental area circuit may be part of the output pathway by which the MPOA influences maternal behavior. (4) MPOA neural circuitry may interact with olfactory neural circuitry and with the motor system to influence maternal responsiveness. (5) Opioid neural pathways appear to inhibit, and oxytocinergic neural pathways appear to promote, maternal behavior. PMID- 2897702 TI - [A new method for the determination of the multiple molecular forms of gamma glutamyltransferases after electrophoresis on cellulose acetate. Preliminary data]. AB - What is described is a new, sensitive, simple and precise method for the visualization of the multiple molecular forms of the gamma-glutamyltransferase by means of electrophoresis on cellulose acetate in parallel with the serum protein pattern. The isoenzymatic pattern in 100 cases with a normal catalytic activity was mainly represented by two bands, one in the alpha 1 region and one in the alpha 2. Also examined was the serum of 103 cases having various hepatic biliary pathologies and a catalytic activity out of the reference interval, in an attempt to evaluate the diagnostic usefulness of the various isoenzyme patterns. PMID- 2897701 TI - Role of primary sensory neurons in the central effects of nicotine. AB - Utilizing single unit recording techniques the nicotine-induced excitation of noradrenaline (NA)-containing neurons in the locus coeruleus (LC) was analyzed. Low doses of nicotine (40-160 micrograms, IV) were found to dose-dependently increase the LC firing rate. The effect was antagonized by pretreatment with the quaternary ganglionic blockers hexamethonium (12 mg/kg, IP) and chlorisondamine (0.3 mg/kg, IV). Also, neonatal treatment with capsaicin, a procedure that is associated with a selective degeneration of primary sensory C-fibre afferents, clearly antagonized the effect of nicotine on LC neurons. The typical effect of nicotine on LC discharge was, in all essentials, mimicked by the quaternary nicotinic agonist tetramethylammonium (TMA). We here propose that the action of nicotine on central NA neurons is primarily executed peripherally via activation of primary sensory C-fibre afferents. PMID- 2897703 TI - Stimulation of lymphocyte function by monoclonal CD2 (E rosette receptor) specific antibodies. PMID- 2897704 TI - [Pleomorphism of panarteritis nodosa. Considerations on an anatomo-clinical case]. PMID- 2897705 TI - Effects of dietary alpha-linolenic acid deficiency during pregnancy and lactation on lipid fatty acid composition of liver and serum in the rat. AB - The effects of a dietary alpha-linolenic acid (18:3 n-3) deficiency on lipid fatty acid composition of the liver and serum of lactating rats have been studied during three gestations and over three generations. These females were compared to corresponding females which remained sterile. Two lots of female rats received, respectively, a diet containing lipids either in the form of 1.50 g of sunflower oil per 100 g of diet (deficient diet) or as 1.87 g of soya oil per 100 g of diet (control diet). Both diet contained the same amount of linoleic acid (18:2 n-6), i.e. 940 mg/100 g of diet, but the sunflower diet supplied 43 times less 18:3 n-3 than the soja diet, or 3 mg vs 130 mg/100 g of diet. Results show that successive gestations appeared to be more efficient means of depleting material n-3 PUFA stores than successive generations. The 18:3 n-3 deficient diet caused a considerable decrease in the level of n-3 polyunsaturated fatty acids (n 3 PUFA) in liver and serum lipids, and particularly of 22:6 n-3. This decline was compensated by an increase in the level of n-6 polyunsaturated fatty acids (n-6 PUFA), and particularly by a very high augmentation of 22:5 n-6. The ratio n-6 PUFA/n-3 PUFA in liver phospholipids and in serum lipids was a good index of the adequacy of dietary n-3 PUFA supply. However, the ratio 22:5 n-6/22:6 n-3 was a finer index. This ratio appeared to be a reliable index of dietary n-3 PUFA deficiency when it was higher than 1 in serum lipids of a fasting animal. The proportion of 22:5 n-6 as well as the ratios n-6/n-3 and 22:5 n-6/22:6 n-3, were also increased in the liver phospholipids of lactating females receiving the soya oil diet; this suggested that a supply of 130 mg/100 g of diet, corresponding to a ratio of n-6/n-3 = 7.2, was not sufficient for these rats during pregnancy and lactation. A supply of 200 mg of n-3 PUFA/100 g of diet, corresponding to a ratio of n-6/n-3 = 5, is recommended for these animals. PMID- 2897706 TI - Estramustine phosphate inhibits germinal vesicle breakdown and induces depolymerization of microtubules in mouse oocyte. AB - The first meiotic cell division (meiotic maturation) of the dictyate stage of mouse oocytes, removed from the follicle, resumes spontaneously in vitro. This study indicates that estramustine phosphate reversibly blocks meiotic maturation by inhibiting germinal vesicle breakdown. Oocyte cryostat sections were stained with anti-tubulin and two antibodies (anti-MAP1: JA2 and 5051) which decorated the metaphase spindle during meiotic maturation. It was found that (1) estramustine phosphate depolymerized microtubules in ovo and dispersed non tubulin antigens associated with microtubules of the metaphase spindle at various stages of maturation, and (2) estramustine phosphate decreased the ability of taxol to induce cytoplasmic asters. These results suggest that germinal vesicle breakdown and microtubule polymerization may be linked. PMID- 2897707 TI - Somatostatin-gastrin interactions in the rat stomach. AB - Low concentrations of somatostatin and gastrin within or slightly above the range of physiologically circulating levels were perfused in the isolated, vascularly perfused rat stomach preparation. Somatostatin at 10 and 50 pg/ml significantly inhibited acetylcholine-stimulated gastrin secretion by 26% and 45%, respectively, whereas perfusion of 50 and 500 pg/ml exogenous gastrin did not modify gastric somatostatin secretion. Perfusion of somatostatin-antiserum significantly increased gastrin release by 235%. It is concluded that (1) somatostatin is a powerful inhibitor of the gastrin cell under in vitro conditions; the data are in accordance with a concept that endogenous somatostatin could act as a true hormone; (2) the secretory activity of the somatostatin cell is not significantly affected by circulating gastrin. PMID- 2897708 TI - Influence of Clostridium perfringens and its toxin in germ-free chickens. AB - Twenty-one of 56 germ-free chickens died after receiving an oral inoculation of a broth culture of Clostridium perfringens. At necropsy there was detachment and disruption of the epithelial layer at the tips of villi and sloughed epithelial cells in the duodenum. These are characteristic lesions of necrotic enteritis. Germ-free chickens receiving either purified alpha-toxin or the supernatant of broth cultures of C perfringens died, but no bird died after receiving supernatant of broth cultures neutralised by anti-alpha-toxin serum. It was concluded that alpha-toxin of C perfringens was the cause of death in young germ free chickens. PMID- 2897709 TI - [The discovery of S2 blockers]. PMID- 2897711 TI - Histamine inhibits interleukin 1 production by lipopolysaccharide-stimulated human peripheral blood monocytes. AB - Histamine inhibited the production of interleukin 1 (IL-1) induced by lipopolysaccharide (LPS) in cultures of purified human peripheral blood monocytes. The effect of histamine on IL-1 production was dose-dependent and significant at histamine concentrations of 10(-4)-10(-5) M. The histamine H2 receptor agonists dimaprit and 4-methylhistamine, but not the H1 receptor agonists 2-pyridylethylamine, aminoethylthiazole and 2-methylhistamine, modulated the IL-1 production in a similar manner to histamine. The inhibitory effects of histamine could be reversed by the H2 receptor antagonist cimetidine but not by the H1 receptor antagonist mepyramine. This indicates that the inhibitory effects of histamine on LPS-induced IL-1 production are mediated through H2 receptors on human peripheral blood monocytes. PMID- 2897712 TI - Activation of human T lymphocytes through CD3 and CD2 (T11) with anti-CD3-coupled sheep erythrocytes. AB - Proliferative activation of T lymphocytes depends on cell-cell cooperation, i.e. interactions between specific cell surface receptors and their ligands. My co workers and I have recently shown that an activating signal is mediated by interaction between the T cell surface antigen CD2 (T11) and its ligand on sheep erythrocytes (SE), the T11 target structure (T11TS), which is the homologue to the human LFA-3 antigen. Here I demonstrate that the anti-CD3 monoclonal antibody (MoAb) UCHT1 coupled to SE (SE-UCHT1) most efficiently induces accessory cell (AC)-independent T cell proliferation, and that SE can substitute for AC in stiumulation with phytohaemagglutinin (PHA). Inhibition studies with MoAb suggest that (1) concurrent stimulation of CD3 and CD2 is essential for interleukin 2 production and proliferation, since SE-UCHT1 treated with the anti-T11TS MoAb L180/1 are not mitogenic; (2) proximity of CD3 and CD2 is required during the stimulation, since a mixture of SE exposing either anti-CD3 or T11TS is not mitogenic; and (3) that T cell-AC interactions involving LFA-1 can be replaced by LFA-3-CD2 interactions, since the anti-LFA-1 MoAb 60.3 does not inhibit the SE UCHT1 response, and only partly the SE + PHA response. These results demonstrate a functional linkage between the CD3 and CD2 structures, making accessory LFA-1 signals superfluous in proliferative activation of human resting peripheral T cell. PMID- 2897710 TI - Beta-adrenoceptor blockade and exercise. An update. AB - Blockade of beta-adrenoceptors interferes with haemodynamic and metabolic adaptations and ion balance during dynamic exercise. After administration of a beta-blocker exercise heart rate is reduced. Exercise cardiac output and blood pressure are reduced also, but to a lesser extent than heart rate. At submaximal exercise intensities blood flow to the active skeletal muscle is also reduced. The availability of non-esterified fatty acids for energy production is decreased, due to inhibition of beta-adrenoceptor-mediated adipose tissue lipolysis, and possibly also of intramuscular triglyceride breakdown. During submaximal exercise muscle glycogenolysis is unaffected, but there are indications that the maximal glycogenolytic rate at high exercise intensities is decreased. In normally fed subjects plasma glucose concentration is maintained at a normal level during submaximal endurance exercise after beta-blocker administration, although lower glucose concentrations are found in fasting subjects and during high intensity exercise after beta-blocker administration. Plasma lactate concentrations tend to be somewhat lower after beta-blocker administration while plasma potassium concentration during exercise is increased. beta-Blocker administration may also interfere with thermoregulation during prolonged exercise. Maximal aerobic exercise capacity is reduced in normotensive and probably also in hypertensive subjects after beta-blocker administration. Submaximal endurance performance is impaired to a much more important extent in both groups of subjects. In patients with coronary artery disease, on the other hand, symptom-limited exercise capacity is improved during beta-blocker treatment. Studies on trainability during beta-blocker treatment show inconsistent results in healthy subjects, although the majority of studies suggest a similar training-induced increase in VO2max during placebo and beta blocker treatment. In patients with coronary artery disease the training effects are also similar in patients treated with beta-blockers and those without. The negative effects of beta-blockers on maximal and especially submaximal exercise capacity should be considered when prescribing beta-blockers to physically active hypertensive patients. The negative influence is shared by all types of beta blockers, although the impairment of submaximal exercise capacity is more pronounced with non-selective than with beta 1-selective beta-blockers. beta Blockers with intrinsic sympathomimetic activity have similar effects during exercise to those without intrinsic sympathomimetic activity. PMID- 2897713 TI - Hormonal control of prostate function. AB - The intention of this article is to provide an introduction to some of the recent concepts within the subject of hormonal regulation of the prostate gland. PMID- 2897714 TI - [ACE inhibitors in the diagnosis and therapy of various forms of hypertension]. AB - The diagnostic and therapeutic aspects of ACE inhibitors in patients with various forms of hypertension are discussed. The immediate blood pressure reduction after administration of an ACE inhibitor is significantly more marked in patients with renovascular than with essential hypertension. However, analysis of the individual blood pressure response after captopril does not allow a clear distinction between these two forms of hypertension. In patients with moderate hypertension the reduction of blood pressure with ACE inhibitors is similar to that with betablockers. Their use as a first step agent in moderate hypertension, however, is limited to selected patients. In severe drug-resistant hypertension treatment with ACE inhibitors is well established. Cases with renovascular hypertension may suffer a deterioration of renal function under ACE inhibitors. Other side effects are uncommon where renal function is normal or where the dose is adapted to the decreased glomerular filtration rate. PMID- 2897715 TI - Expression of the beta-nerve growth factor gene in hippocampal neurons. AB - In situ hybridization with complementary DNA probes for nerve growth factor (NGF) was used to identify cells containing NGF messenger RNA in rat and mouse brain. The most intense labeling occurred in hippocampus, where hybridizing neurons were found in the dentate gyrus and the pyramidal cell layer. The neuronal identity of NGF mRNA-containing cells was further assessed by a loss of NGF-hybridizing mRNA in hippocampal areas where neurons had been destroyed by kainic acid or colchicine. RNA blot analysis also revealed a considerable decrease in the level of NGF mRNA in rat dentate gyrus after a lesion was produced by colchicine. This lesion also caused a decrease in the level of Thy-1 mRNA and an increase in the level of glial fibrillary acidic protein mRNA. Neuronal death was thus associated with the disappearance of NGF mRNA. These results suggest a synthesis of NGF by neurons in the brain and imply that, in hippocampus, NGF influences NGF-sensitive neurons through neuron-to-neuron interactions. PMID- 2897716 TI - Chloroplast transformation in Chlamydomonas with high velocity microprojectiles. AB - Bombardment of three mutants of the chloroplast atpB gene of Chlamydomonas reinhardtii with high-velocity tungsten microprojectiles that were coated with cloned chloroplast DNA carrying the wild-type gene permanently restored the photosynthetic capacity of the algae. In most transformants of one of the mutants, a fragment with a 2.5-kilobase deletion was restored to normal size by a homologous replacement event; in about 25 percent of the transformants the restored restriction fragment was 50 to 100 base pairs smaller or larger than that of wild type. About one-fourth of the transformants of this mutant contained unintegrated donor plasmid when first examined. This plasmid persisted in four different transformants after 65 cell generations of continuous liquid culture but was lost from all transformants maintained on plates of selective medium. The restored wild-type atpB gene remains in all transformants as an integral part of the chloroplast genome and is expressed and inherited normally. PMID- 2897717 TI - Inhibition of cellular proliferation by antisense oligodeoxynucleotides to PCNA cyclin. AB - The proliferating cell nuclear antigen (PCNA or cyclin) is a nuclear protein recently identified as a cofactor of DNA polymerase delta. When exponentially growing Balb/c3T3 cells are exposed to antisense oligodeoxynucleotides to PCNA, both DNA synthesis and mitosis are completely suppressed. A corresponding sense oligodeoxynucleotide has no inhibitory effects. These experiments indicate that PCNA (cyclin) is important in cellular DNA synthesis and in cell cycle progression. PMID- 2897719 TI - Alfentanil in outpatient ENT surgery. PMID- 2897718 TI - "Bicycle kickstand" phenomenon: prolonged erections associated with antipsychotic agents. AB - The purpose of this paper is to draw attention to the ability of some antipsychotic agents to produce sustained erection short of priapism. They appear to have this effect consistently over time in some individuals. The effect is rapidly reversible on discontinuation of the drug, and appears to be dose dependent. In one of our patients, the "active metabolite" of that same drug could not duplicate the effect. Prevalence and mechanism require clarification. If even a small proportion of patients with the sustained erection phenomenon are found to progress to priapism, this would have profound ramifications. If this phenomenon could be confidently predicted or safely and readily implemented, the benefits for some patients with impotence or premature ejaculation might be considerable. Given all the potential adverse side effects of antipsychotics, it should be appreciated that the potential direct effects on male sexual function are not always adverse. PMID- 2897720 TI - Teratogenicity of N-(4-hydroxyphenyl)-all-trans-retinamide in rats and rabbits. AB - N-(4-hydroxyphenyl)-all-trans-retinamide (HPR) has potential efficacy in the treatment of dermatologic, arthritic, and neoplastic disorders. The teratogenicity of such a compound is of special concern in light of the known adverse effects of retinoids, in general, on the developing conceptus. In these studies, Sprague-Dawley rats and New Zealand White rabbits were treated orally from gestation days 6 to 15 and 6 to 18, respectively, with 0, 20, 125, or 800 mg/kg/day of HPR. In rat fetuses, low incidences of hydrocephaly (mid- and high dosage groups) were observed. Fetal tissue (ng/g) and maternal plasma (ng/ml) concentrations of HPR, its major metabolite (N-[4-methoxyphenyl] retinamide [MPR]) and retinol were determined in separate groups of similarly-treated rats 3 h following the last dose on gestation day 15. Fetal tissue concentrations of HPR and MPR were approximately one-half maternal plasma concentrations. A dose related reduction in maternal plasma and fetal tissue concentrations of retinol were also observed. In mid- and high-dosage rabbit fetuses, a dose-related increase in the incidence of dome-shaped head was observed. Subsequent skeletal evaluation revealed delays in skull bone ossification and a widening of the frontal and frontoparietal sutures. Microphthalmia was also observed in two high dosage fetuses. A dose-dependent and statistically significant reduction in maternal plasma retinol levels was observed across all dosage groups. PMID- 2897721 TI - Prenatal and postnatal thallium exposure in rats: effect on development of vasomotor reactivity in pups. AB - Vasomotor reactivity has been evaluated in rats exposed perinatally and postnatally to thallium sulphate (1 mg/dl in their drinking water ad libitum). Prenatal and postnatal exposure to thallium did not modify the values of the systolic arterial blood pressure on the 30th and 60th day in pups of normotensive and DOCA-hypertensive rats. The hypertensive responses induced by endosinusal carotid hypotension and by 1-noradrenaline in pups of normotensive and DOCA hypertensive rats, exposed or not exposed to thallium sulphate, were more intensive on the 60th than on the 30th day. Similar effects were observed for the hypotensive responses induced by 1-isoprenaline and acetylcholine. Prenatal exposure to thallium did not modify hypertensive responses induced by endosinusal carotid hypotension on the 30th and 60th days, but it caused a decrease of hypertensive responses induced by 1-noradrenaline on the 30th and 60th days and hypotensive responses induced by 1-isoprenaline and acetylcholine exclusively on the 60th day. Postnatal exposure to thallium did not modify hypertensive responses induced by endosinusal carotid hypotension and hypotensive responses induced by acetylcholine, but it caused a decrease of hypertensive responses induced by 1-noradrenaline on the 30th and 60th days in pups of normotensive rats and exclusively on the 60th day in pups of DOCA-hypertensive rats. Moreover, postnatal exposure to thallium caused a decrease of the hypotensive response induced by 1-isoprenaline exclusively on the 60th day. Our findings show that prenatal and postnatal exposure to thallium sulphate modifies the rat's developing vascular autonomic nervous system with a reduction of the alpha, beta adrenergic and muscarinic vasomotor reactivity. PMID- 2897722 TI - Multiple abnormalities in the ultraviolet light response of cultured fibroblasts derived from patients with the basal cell nevus syndrome. AB - Basal Cell Nevus Syndrome (BCNS) is a rare autosomal-dominant inherited disorder associated with a marked hypersusceptibility to spontaneous and radiation-induced skin cancer. We examined the changes in cell survival, unscheduled DNA synthesis (UDS) and the frequency of sister chromatid exchanges (SCE) induced by ultraviolet light (UVL) in confluent normal and BCNS fibroblasts. BCNS cells appeared slightly hypersensitive to the cytotoxic effects of UVL. The rate of UDS induced by UVL exposure in normal cell strains increased linearly following doses up to 30 J/m2, whereas in BCNS cells UDS became saturated at doses of 10 J/m2 showing no further increase with doses up to 30 J/m2. UDS activity persisted for longer periods after UVL exposure in BCNS as compared with normal cells. The dose response relationship for UVL-induced SCE was similar in normal and BCNS fibroblasts. However, the frequencies of UVL-induced SCE declined to near background levels in normal cells following 12-24 hr of confluent holding prior to subculture whereas they remained elevated in BCNS cells with holding times up to 24 hr after UVL exposure. Overall, these results suggest that BCNS fibroblasts may have a diminished capacity for the repair of some type of DNA damage as compared with normal fibroblasts. PMID- 2897723 TI - Mutagenicity and carcinogenicity studies of homemade "rust-proof cutting fluid". AB - A homemade rust-proof cutting fluid (RPCF) used in China was tested for carcinogenicity by an in vivo chronic experiment and for mutagenicity by the Ames Salmonella microsomal assay. Undiluted and threefold water-diluted fluid were given as drinking water to groups of young adult Wistar rats for 2 years. The treatment induced 11/40 malignant tumors with 9/40 acinar adenocarcinomas of the pancreas in the high-dose group. Simultaneous administration of ascorbic acid dissolved in the undiluted fluid at 2 g acid per 1 g sodium nitrite resulted in 1/40 pancreatic carcinoma. The results of the Ames test showed that the technical RPCF was mutagenic to TA100 with or without metabolic activation. It was concluded that the homemade RPCF, which is comprised of sodium nitrite, triethanolamine, and polyethylene glycol, may form direct-acting mutagen(s) upon storage and form, in vivo, e.g., nitrosamines that caused acinar pancreatic carcinoma in Wistar rats. Simultaneous administration of ascorbic acid is suggested for the protection of workers exposed to the rust-proof cutting fluid. PMID- 2897724 TI - Qualitative analysis of chromosomal evolution in a colcemid-treated Chinese hamster population. AB - Colcemid is known to inhibit the spindle formation and to induce polyploidy and chromosomal nondisjunction. Using a V79 Chinese hamster cell line, we have shown that colcemid is able to induce the formation of cells that are numerically diploid but whose karyotype, when analyzed with the G-banding technique, differs from that of the untreated ones. Even though these cells have a normal chromosomal constitution, they carry alterations in the chromosomal balance and, consequently, in gene dosage. This could result in an abnormal expression of cellular genes or in the expression of new or preexisting recessive mutations, even in a diploid chromosomal constitution. PMID- 2897725 TI - Dominant lethality in mice--a test for mutagenicity of influenza X-31 virus. AB - The induction of dominant lethal mutation in germ cells is the cause of embryonic death resulting in the reduction of litter size in the F1 progeny. Dominant lethal mutations were induced when male mice were infected with live A2 influenza virus. The chromosomal aberrations induced in the germ cells were shown to be responsible for the dominant lethality. Killed influenza virus was also potent in inducing chromosomal aberrations in spermatocytes of mice. In light of these observations, the UV-inactivated virus was tested for its potency in induction of dominant lethality in both female and male germ cells. The virus-inoculated females were mated with uninjected males and vice versa. Both the inactivated and live virus were found to induce dominant lethality in both female and male mice, indicating that not only the live virus but also the inactivated virus is capable of bringing about chromosomal damage resulting in dominant lethality. PMID- 2897726 TI - Population dynamics of mosquito-borne disease: persistence in a completely heterogeneous environment. AB - We investigate the persistence of a mosquito-borne disease (malaria) in a system where mosquitoes and hosts are grouped in patches containing any number of individuals. A mosquito from any one of vector patches can bite, and take blood meals, in any one of m host patches. We confirm our earlier result (C. Dye and G. Hasibeder, 1986, Trans. R. Soc. Trop. Med. Hyg. 80, 69-77) that nonhomogeneous host selection by mosquitoes leads to basic reproductive rates (which measure the persistence of infection in the system) greater than or equal to those obtained under uniform host selection. We find, in addition, that strong associations between particular groups of mosquitoes and hosts lead to still higher basic reproductive rates. Exacting fieldwork would be required to find out how much higher. PMID- 2897727 TI - Association of HLA-DRBr with HLA-DQw3. AB - The antigen HLA-DRBr, previously associated with HLA-DQw1, has been found by RFLP to be associated with HLA-DQw3. PMID- 2897728 TI - HLA-DR typing using restriction fragment length polymorphism (RFLP) with one enzyme and two probes. AB - A panel of 43 homozygous and 36 heterozygous highly selected cells, representing the most common DR-specificities, were investigated with the DNA hybridization technique. By using a single restriction enzyme, TaqI, and two probes, DR beta and DQ alpha, it was possible to construct assignment criteria giving a reasonable definition of DR1, 3, 4, 5, 7 + w9, w8, w10 and w11. The criteria sometimes require that certain bands must not be present. Therefore, in certain genotypic combinations, the presence or absence of the particular specificity on one haplotype cannot be decided. This is a problem only for DR2 and DRw6, which for this reason cannot be assigned in about 1/3 to 1/4 of the cases. The association between RFLP assignment and serological assignment is not absolute, the correlation coefficients ranking from 0.62 to 1.0. In the case of false negative RFLP assignment, this may be due to genetic heterogeneity, as in the case of a DR2 individual who proved to be Dw12 and not Dw2 associated. It is often stated that interpretation of the RFLP pattern is particularly difficult in random or heterozygous individuals compared to proven homozygotes. This is not the case in the present study, where in fact correlation coefficients between RFLP and serologically determined DR specificities were higher in the heterozygotes (range 0.79-1.00). PMID- 2897729 TI - Protection against acute hyperammonemia: the role of quaternary amines. AB - The quaternary amine L-carnitine is able to protect Swiss Albino mice from hyperammonemia when administered in high doses before ammonium acetate. This has been explained by its specific ability to shuttle fatty acids into mitochondria. The structure of L-carnitine resembles the chemical structure of other substances that have been described as being able to protect living cells against osmotic stress. We subjected Swiss Albino mice to hyperammonemia after pretreatment with L-carnitine or "osmoprotectants" such as the quaternary amines choline and betaine, and trimethylamine N-oxide. L-Carnitine proved to be the drug of choice to protect against acute hyperammonemia. Nevertheless, the other tested compounds appeared also to be effective, suggesting that osmoregulation plays a major role in protection against hyperammonemia. PMID- 2897730 TI - EEG as a neurotoxicological indicator. AB - In living organisms both chemical agents and physical factors [16] may produce neurophysiological change that affects EEG activity. EEG signals are very suitable for non-invasive measurement of CNS reactions, but quite complicated equipment is necessary for measurement and analysis. We have implemented a system that permits the study of EEG changes both in time and frequency domains using broad-band analysis or fast Fourier transformation (FFT). Experimental animals were influenced by high doses of toxic agents (CO, CS2, barbiturates, pesticides), drugs and both non-ionizing and ionizing radiation. The EEG changes reflecting the influencing factor, respectively its quantity may be divided into several classes: (1) appearance of new activities; (2) disappearance of some activities; (3) increase of amplitudes, respectively spectral power densities (SPD) in certain frequencies; and (4) decrease of amplitudes, respectively SPD in certain frequencies. All changes are related to the controls, i.e. to the relatively normal state of CNS. Furthermore it is possible to investigate the temporal dynamics of these changes. Physiological concordance of these findings is sometimes possible from clinical analogues, but in other cases is unknown and considerable effort will be necessary to elucidate these correlates. Anyhow in some toxic substances, the EEG may be quite insensitive as an indicator of neurotoxicity. The best way to solve these problems is to collect sufficient experimental data for complex analysis. Although few relevant data are currently available, temporal and frequency domain measures of EEG activity appear to have promise as neurotoxicity indicators. PMID- 2897731 TI - Interactions of neurotoxicants with neurotransmitter systems. AB - Many neurotoxic compounds have been shown to interfere with neurotransmission both in vitro and following acute and chronic administration. Various parameters of neurotransmission can be directly affected by neurotoxicants; these include the enzyme(s) synthesizing a neurotransmitter, the release and uptake processes, the enzyme(s) which metabolize the neurotransmitter, the receptors, and post synaptic events associated with receptor activation. Some neurotoxicants can interfere with neurotransmission indirectly, by interacting for example with energy metabolism, sodium channels or ATPases. Furthermore, measured alterations of any parameter of neurotransmission can be the result of neuronal death, due to a cytotoxic effect of the neurotoxicants. Chemicals which have been shown to alter neurotransmission include solvents (e.g. carbon disulfide), metals and organometals (e.g. lead, mercury, trimethyltin) and pesticides (e.g. organophosphates, pyrethroids, organochlorines, formamidines). An example of the various alterations in neurotransmitter parameters, which can occur following acute or chronic administration, is represented by the organophosphates. Organophosphorus insecticides owe their acute toxicity to inhibition of acetylcholinesterase and accumulation of acetylcholine at cholinergic receptors. Chronic exposure to these compounds results in the development of tolerance to their toxicity which is associated with a decrease in the density of muscarinic and nicotinic receptors in both the central and peripheral nervous system. Other examples of the interactions of neurotoxicants with neurotransmitters are also described. PMID- 2897732 TI - [Treatment of soft-tissue injuries of the face and mouth]. PMID- 2897733 TI - Platelet activity and selective beta-blockade in migraine prophylaxis. AB - Migraine is associated with increased platelet activity and an incidence of cerebrovascular ischemic events. Because cerebrovascular events might result from platelet aggregation, enhancing platelet activity further in the treatment of migraine is not desirable. beta-Adrenoceptor blockers effective in migraine prophylaxis include propranolol (nonselective) and metoprolol (beta 1-selective), but it is uncertain how beta-receptor subtype selectivity might influence platelet behavior in migraine. In 29 patients, comparable clinical responses were obtained with therapeutic doses during 1 month of treatment with propranolol, metoprolol, and the beta 2-selective Li 32-468. Propranolol increased and metoprolol decreased platelet aggregation and ATP release, and the effect of Li 32-468 could be related to that of propranolol. These actions can be largely explained in terms of what is known of platelet beta-receptors and therefore can be generalized to other effective beta-blockers. Since altered platelet activity does not account for the efficacy of these agents in migraine, the actions of beta-blockers on platelets should be considered as side effects. Those beta blockers inhibiting platelet activity should be preferred in migraine treatment, assuming equal efficacy, which implies the use of beta 1-selective blockers. PMID- 2897734 TI - [Long-term treatment of acromegaly with a somatostatin analog]. PMID- 2897735 TI - [The treatment of acute myocardial infarct in Denmark]. PMID- 2897736 TI - [Concept in the treatment of pain in patients with cancers]. AB - Pain in cancer patients is shown to arise in different ways, demanding a flexible approach to treatment. The following procedures can be selected from, depending on the origin of the pain. (1) Systemic analgesia with peripheral or central analgesic agents combined with psychotropic preparation; (2) administration of opioids through peridural or intrathecal catheters (for pain responsive to opioids, but side effects considerable); (3) neurolyses, e.g. epigastric tumors, recurrence of rectal carcinoma; (4) cordotomy, e.g. unilateral pain in plexus infiltration; (5) operations (endoprostheses, bridging osteosynthesis in the case of bone metastases with or without fractures); (6) radiotherapy (strontium in the case of multiple bone metastases of some tumors). Other treatment methods, e.g. administration of karsil or cortisone, as adjuvant therapy require further investigation. PMID- 2897737 TI - [Peridural opioid analgesia in the terminal stage of cancer. Indications- implementation--results]. AB - The indications for the application of opioids near the spinal cord are presented and two groups of patients treated with pericutaneous and intracorporeal systems are reported. If indicated, this method offers the possibility of treating patients on an outpatient basis. PMID- 2897738 TI - Haemolytic patterns for presumptive identification of Clostridium perfringens type C. PMID- 2897739 TI - Inheritance of K88-mediated adhesion of Escherichia coli to jejunal brush borders in pigs: a genetic analysis. AB - The transmission and genetic organization of the adhesion of the serological variants of the K88 adhesin in the jejunum of the pig were investigated. The results of 28 matings of 5 boars with 15 sows are presented. On the basis of previous studies it has been accepted that the presence of specific receptor sites for K88ab and K88ac depends on a gene locus with 2 alleles S and s. The presence of additional receptor sites for K88ad is now presumed to depend on a separate locus with the alleles D and d. The expression of the alleles of the S and D loci is not always complete and is likely to be influenced by epistatic genes. Inhibition or modification of the expression of the receptor sites for K88 can result in intermediate phenotypes. PMID- 2897740 TI - Lectin-binding in normal and osteoarthrotic articular cartilage from STR/1N-mouse knee joints. AB - Fluorescein-isothiocyanate (FITC) labeled lectins were used to study the distribution pattern of specific binding-sites in histological sections of normal and osteoarthrotic articular cartilage from the mouse knee joint. Male inbred mice of the STR/1N-strain develop spontaneous arthrotic articular cartilage lesions on the medial condyle of tibia and femur. The varus-deformity of the knee joint leads to a recurrent medial patellar luxation with osteoarthrotic defects on the medial part of the facies patellaris femoris. It was demonstrated that the lectin staining pattern of osteoarthrotic articular cartilage, especially on the facies patellaris femoris, was different from that of normal articular cartilage. The differences in lectin staining corresponded to those observed between normal and fibrillated articular cartilage from human patellae. The normal articular cartilage of the mouse knee joint possessed lectin binding-sites for Concanavalin A (ConA) and wheat germ agglutinin (WGA), but not for Ulex europaeus agglutinin (UEA), soy bean agglutinin (SBA) and peanut agglutinin (PNA). In addition to the completely changed distribution pattern of ConA and WGA in osteoarthrotic cartilage, SBA, PNA and UEA developed distinct staining patterns particular to the fibrillated areas of arthrotic cartilage. The increased lectin-binding to arthrotic articular cartilage may be due to unmasking of sugars in the course of bondage breakdown in fibrillated cartilage or the production of pathological glycoproteins. It is evident that lectins can demonstrate minute differences between normal and arthrotic cartilage and it is concluded, therefore, that lectins are sensitive and specific tools for the study of degenerative joint diseases. PMID- 2897741 TI - Interphasic nucleolar organizer region distribution as a diagnostic parameter to differentiate benign from malignant epithelial tumors of human intestine. AB - The distribution of the interphasic nucleolar organizer regions (NORs) has been investigated in five hyperplastic polyps, five adenomatous polyps and fifteen colonic adenocarcinomas. The study was performed using electron microscopy and paraffin-embedded sections stained for Ag-NOR proteins. Malignant tumor cells were characterized by a large number of NORs which were small in size and showed a scattered distribution. Nuclei of both types of polyp had only a small number of large-sized NORs in a clustered distribution. In two adenomatous polyps, cells were also observed with an NOR distribution pattern intermediate between that of frankly benign and malignant lesions. PMID- 2897742 TI - Morphometric and cytophotometric nuclear analysis of altered hepatocyte foci induced by N-nitrosomorpholine (NNM) and aflatoxin B1 (AFB1) in liver of Wistar rats. AB - The progressive morphological changes in the liver during neoplastic transformation have been studied by histological, cytophotometric and morphometric methods in male Wistar rats treated with two carcinogens: N nitrosomorpholine (NNM) and aflatoxin B1 (AFB1). Cytophotometric and morphometric analysis of hepatocyte nuclei using Feulgen-stained tissue sections were performed in morphologically normal hepatic parenchyma and in early preneoplastic foci composed of altered hepatocytes. Foci of clear cells, mixed cells and large basophilic cells possessed a ploidy distribution similar to the surrounding non transformed parenchyma, while the small hyperbasophilic cell foci were predominantly diploid. These findings confirm that the foci composed of PAS negative, small hyperbasophilic cells with an unique diploid content may represent one of the earliest stages in the neoplastic transformation. PMID- 2897743 TI - The restoration of proliferation and differentiation of peripheral blood mononuclear non-adherent cells into immunoglobulin-secreting cells by autologous synovial adherent cells from patients with rheumatoid arthritis. AB - The ability of enzyme-dissociated synovial adherent cells (SAC) obtained from patients with active rheumatoid arthritis to restore the proliferation and differention of peripheral blood mononuclear non-adherent cells (NAC) into immunoglobulin-secreting cells (ISC) was investigated. Autologous combinations of cells were used in this study to eliminate allogeneic reactions. Peripheral blood NAC, prepared by glass adherence and leucine methylester treatment to remove monocytes, almost completely lost their capacity to proliferate and differentiate into ISC in response to pokeweed mitogen. The response of NAC was restored by adding 12.5% of 'fresh SAC', which was obtained by glass-adherence after an overnight culture of non-rosette forming, enzyme-dissociated rheumatoid synovial cells. Although the response was also restorable by adding more than 25% fresh SAC, this was less satisfactory than adding 12.5% SAC. 'Old SAC', obtained by glass-adherence after 7 days culture of enzyme-dissociated synovial cells, did not restore the response of NAC. Immunohistochemical studies showed that 55% of fresh SAC and 3% of old SAC expressed HLA-DR antigens. When 100 units/ml of interferon gamma was present, 25% of old SAC remained HLA-DR-positive and some of these cells retained a dendritic morphology after 7 days culture. The results indicate that rheumatoid synovia contain macrophage-like cells that can effectively support the ultimate differentiation of lymphocytes to ISC. PMID- 2897744 TI - Short-term effects of carbon tetrachloride on the lipoprotein secretion in isolated rat hepatocytes. AB - Short-term exposure of isolated rat hepatocytes in suspension to a low dose of CCl4 (20 micrograms/ml) leads within minutes to characteristic structural alterations. The earliest reaction is a disappearance of the microvilli border 5 min after starting the incubation. After 10 min the number of Golgi VLDL is decreased by about 80% and reaches zero after 20 min. The reduction in Golgi VLDL is associated with a decrease in the volume density of the Golgi complexes by about 50% compared with controls and by a marked elevation of intracytoplasmic and intralysosomal lipid deposits after 20 min incubation. Concomitantly with these alterations the total number of VLDL particles within single and multiple particle secretory vesicles located along the cell periphery decreases by about 50% 10 min after CCl4 exposure. This is followed 10 min later by a significant increase of about 20% compared with the corresponding controls. The elevation in the total number of VLDL is combined with an increase in the number of the multiple particle secretory vesicles. The particle content per vesicle, however; is significantly lower compared with controls. No reaction is detectable in the mitochondria, whereas the amount of RER appears to be decreased and that of the SER increased. The incubation of 14C-sodium palmitate prelabeled hepatocytes in the presence of CCl4 leads to a significantly higher content of labeled lipids in the total Golgi fraction and in the cytosol 20 min after CCl4 administration, whereas considerably less labeled lipids are secreted into the incubation medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897745 TI - Immunohistochemical localization by monoclonal antibodies of S-100 alpha and beta proteins in mixed tumours and adenomas of the skin. AB - A study using monoclonal antibodies was made to evaluate the immunohistochemical localization of S-100 protein subunits alpha and beta in a total of 41 mixed tumours and adenomas of sweat gland origin. Normal eccrine glands showed positive staining for S-100 alpha in the secretory portion and in epithelial cells located in the transitional area from the coiled duct to the intraepidermal duct, as well as granular deposition of S-100 beta at the luminal surface of the secretory coil and duct. The myoepithelial cells were negative for S-100 alpha and beta. In mixed tumours, the tumour cells were round or oval in shape and displayed markedly positive staining for S-100 alpha and slightly positive or negative staining for S-100 beta. S-100 alpha staining in clear cell tumours was typically more intense than in any other sweat gland tumour. It is possible that clear cell tumours may arise from the transitional area of sweat glands. Spindle cell tumours displayed on abundance of S-100 alpha subunits but little S-100 beta. Occasional spindle cells located in the outer layer of tubular structures within tumours gave positive S-100 alpha staining. This result was different from that seen in pleomorphic salivary adenomas. Cells having undergone chondroidal changes revealed a positive S-100 reaction. PMID- 2897746 TI - [Graves-Basedow disease: current aspects of the diagnosis and treatment]. PMID- 2897747 TI - [Effect of diazepam and analeptics on the structure of sleep in the cat]. PMID- 2897748 TI - [The free myocutaneous latissimus dorsi flap in functional rehabilitation of the lower extremity]. PMID- 2897749 TI - [Microbiological research methods of drinking water regulation in West Germany from 1986. Suitability of the specifications of DIN 38411, Part 7, for the detection of sulfite-reducing, spore-forming anaerobes (Clostridia)]. AB - The drinking-water regulations of the Federal Republic of Germany, from 22.05.1986, contains in paragraph 1 the instructions: "Drinking-water must be free of pathogens", and further in paragraph 11, "Responsibilities of the employer or other owner of a water supplying facility", include that: "The official authority may direct, that the employer...of a water supplying facility has to extend or has to cause to extend the microbiological examinations in order to determine, that...sulfite-reducing, spore-forming anaerobes (Clostridia) can not be detected in 20 ml of water..." The drinking-water regulations do not prescribe a bacteriological examination method in detail. Appendix 1 rules only that the examination for sulfite-reducing, spore-forming anaerobes (Clostridia) has to be performed after heating the sample to 75 degrees C (+/- 5 degrees C) for 10 min, by either the multiple-tube or membrane filtration method and cultivation in DRCM1-medium. If growth occurs, the presence of Clostridia must be confirmed by anaerobic and aerobic subcultivation. Furthermore, a DIN-instruction (DIN 38411, part 7) exists, which prescribes a detailed procedure for multiple tube and membrane filtration methods, but does not provide for strict anaerobiosis. We were, however, unable to detect Clostridia in a multitude of water samples with the methods of the DIN-regulation. In order to examine if neglect of strict anaerobiosis was the reason for these failures, we checked the suitability of the DIN-regulation for the isolation of Clostridia from drinking water. In preliminary tests we examined up to four strains of the species C. botulinum, C. cadaveris, C. cochlearium, C. difficile, C. innocuum, C. perfringens and C. tertium for their ability to form heat-resistent spores in four sporulation media. It was, however, not possible to find a medium, in which all strains could sporulate within one week. In order to characterize the detection of these anaerobes in water, one particularly well-sporulating strain of each of the following, C. cadaveris, C. difficile and C. perfringens, was selected and the multiple-tube and membrane-filtration methods were compared. Counts of C. difficile and C. perfringens detected by the multiple-tube method were identical with counts of test-suspensions determinded by the most probable number (MPN) method. It was found to be decisive that only freshly prepared DRCM medium be used and that, disagreeing with the DIN-instruction, cultivation at 37 degrees C is continued for at least four days.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2897750 TI - [Tardive dyskinesia (review of the literature)]. PMID- 2897751 TI - The possible role of homeotic genes in the causation of malformations in monozygotic twins. AB - It is proposed that the malformations observed to occur with increased frequency in monozygotic twins are similar to the types of malformations caused by mutation in homeotic genes in animals. PMID- 2897752 TI - Immunohistochemical hormone content in medullary and undifferentiated thyroid carcinoma and prognosis after surgery. AB - Immunohistochemical determinations in tissue specimens of medullary and "undifferentiated" thyroid carcinomas were carried out with antisera against calcitonin, calcitonin-gene related peptide (CGRP), somatostatin, and also thyroglobulin, using the PAP method. All 8 samples of medullary carcinoma stained positive with antisera against calcitonin and CGRP, 7 samples were also positive for somatostatin. Out of 22 cases initially diagnosed as "undifferentiated thyroid carcinoma" 3 revealed positivity for calcitonin, 2 for CGRP, and 1 for somatostatin. Congo red stain for amyloid, performed several years ago in 2 of these 3 cases, had been negative. The patients with medullary carcinoma survived longer than those with "undifferentiated" carcinoma. One patient of the latter group, but with calcitonin, CGRP, and somatostatin immunoreactivity in the tumour tissue, is now alive and well, more than 4 a after initial treatment. PMID- 2897753 TI - Opioids in anaesthesia. PMID- 2897754 TI - Reduced tyrosine hydroxylase-like immunoreactivity around cerebral arteries after experimental subarachnoid hemorrhage in rats. An immunohistochemical study. AB - In a subarachnoid hemorrhage (SAH) model of the rat, there is a decreased tyrosine hydroxylase-like immunoreactivity in the adrenergic nerves around cerebral arteries. No altered reactivity is found in the superior cervical ganglion or in the nerve bundles around the internal carotid artery of cervical portion. The results suggest that SAH impairs the initial step of catecholamine synthesis in the adrenergic nerves within the subarachnoid space. PMID- 2897755 TI - [Effects of ginseng root saponins on central transmitters and plasma corticosterone in cold stress mice and rats]. PMID- 2897756 TI - [Radioimmunoassay for dynorphin A 1-13]. PMID- 2897757 TI - [Arrhythmogenic effects of histamine on ischemic hearts of guinea pigs]. PMID- 2897758 TI - The dopamine systems in the brain, functional classification of different dopamine receptors. AB - Dopamine (DA) acts as a neurotransmitter in the central nervous system. The main part of the DA cell bodies are localized in the ventral mesencephalon and their axons run together in the medial forebrain bundle before diverging to different terminal areas in the forebrain, like the nucleus caudatus-putamen, nucleus accumbens, septum, amygdala, and several cortical areas like the cingulate, pyriform, entorhinal and prefrontal cortices. The functions of the dopamine systems are discussed in terms of how dopamine can modulate the functions of the area it innervates. Changes in dopaminergic transmission may be found after animals have been exposed to stress. This has implications for the discussion of whether a changed dopaminergic transmission in schizophrenia is a cause to, or a consequence of the disease. Both theories proposing a single localized anatomical site of action for the antipsychotic effect of neuroleptic drugs as well as those implicating a general effect on a number of different regions have been put forward. It is now widely accepted that there exists two classes of DA receptors, the D-1 and D-2 receptors, which have different physiological, and therefore proposed to have different clinical, characteristics. Other research implies however that a subpopulation of D-2 receptors is most important for the antipsychotic effect. PMID- 2897759 TI - Receptor pharmacology. Its use in neuroleptic research. AB - Dopamine D-1 and D-2 receptors can be labelled selectively by using 3H-SCH 23390 and 3H-Spiperone as ligands, respectively. Neuroleptics are divided into different groups according to their affinity for D-1 and D-2 receptors. Thioxanthenes have comparable affinities for D-1 and D-2 receptors. Phenothiazines have higher affinity for D-2 than for D-1 receptors. Butyrophenones, diphenylbutylpiperidines and substituted benzamides are almost selective inhibitors of D-2 receptors. The affinity of neuroleptics for several other receptor types is mentioned. The use of the receptor binding technique in diseased schizophrenics is discussed. In vivo receptor binding in vitro and ex vivo receptor autoradiography and PET scanning are discussed as alternative methods to evaluate neuroleptics, clinical outcome and treatment strategies. PMID- 2897760 TI - Central dopaminergic mechanisms in schizophrenia. AB - A neurochemical evaluation of the dopamine hypothesis of schizophrenia has been carried out. There was no evidence to suggest that the synthesis or inactivation of dopamine was abnormal in schizophrenia. The brain concentrations of the amine itself, its metabolities and the activities of its related enzymes were similar in controls and schizophrenics. However in vitro and in vivo evidence is presented that suggests that the illness may be associated with an increase in the numbers of dopamine D2 receptors in the brain. PMID- 2897761 TI - Neuroleptic-induced tardive dyskinesia. AB - Prolonged exposure to neuroleptic drugs induces tardive dyskinesia which may be persistent or permanent. Predisposing factors to tardive dyskinesia are not apparent although the aging brain appears more vulnerable. The drug treatment of tardive dyskinesia is at present unsatisfactory. Preventive measures, other than limiting neuroleptic use have not been established. The pathophysiology of tardive dyskinesia may relate to cerebral dopamine overactivity. However, although this may be a primary change responsible for tardive dyskinesia alterations in other neuronal systems such as acetylcholine, 5HT or GABA may be involved. PMID- 2897762 TI - Psychoneuroimmunology and neuroimmunomodulation. An outline of some recent developments presented at the Second International Workshop on Neuroimmunomodulation. AB - Recent developments of Psychoneuroimmunology and Neuroimmunomodulation presented at the Second International Workshop on Neuroimmunomodulation (Dubrovnik 1-6 June 1986) are summarized. The bidirectional nature of the relationship between the central nervous system and the immune system is stressed. PMID- 2897763 TI - Analgesic treatment in acute myocardial infarction. A double-blind comparison of ketobemidone + the spasmolytic A29 (Ketogan) and morphine. AB - The analgesic effect of ketobemidone hydrochloride + the spasmolytic component A29 (Ketogan) and morphine hydrochloride was compared double-blindly in patients with suspect acute myocardial infarction. The test drugs were administered i.v. in an initial dose of 0.5 ml (2.5 mg Ketogan, 5 mg morphine) followed, if necessary, by additional injections of 0.25 ml. Altogether, 309 patients participated in the trial. The total consumption of the test drugs showed that 5 mg Ketogan was equipotent with 10 mg of morphine. Treatment with Ketogan resulted in a significantly higher proportion of patients who were completely free of pain 15 and 30 min after the initial injection: 16% and 15% more, respectively, compared to morphine. Within 2 hours after the initial injection, approximately 15% of the patients in both treatment groups had reported nausea and about 7% had vomited (patients who vomited or were nauseated before treatment were not included in this analysis). The frequency of other side-effects was low, with no differences between the two treatment groups. Morphine caused a greater reduction of the systolic blood pressure than Ketogan. The effect of both drugs on pulse rate and respiration was the same. PMID- 2897764 TI - Responsiveness to diving reflex after acute myocardial infarction. Influence of early beta-adrenoceptor blocker therapy. AB - We studied the influence of beta-adrenoceptor blockade on heart rate responses to facial immersion in ice-cooled water after acute myocardial infarction. Forty patients with acute myocardial infarction were randomized to the double-blind therapy with metoprolol 200 mg daily or matching placebo. Therapy was started as soon as possible after admission to hospital and continued for 15 days. After this initial period all patients were treated with beta-blockade during the subsequent 6 months. Repeated investigations of heart rate responses to facial immersion in ice-cooled water and 24-hour ECG-recordings were performed on day 15 (while patients were on study therapy), after 6 weeks, 3 and 6 months. Throughout the 6-month period, facial immersion elicited significant heart rate reductions in both treatment groups. No differences were found between the two groups or between different examinations during follow-up. There was no correlation between heart rate response to facial immersion and frequency of ventricular arrhythmia on a 24-hour monitoring. In conclusion, acute administration of metoprolol in myocardial infarction does not influence the bradycardial response to facial immersion either in the early postinfarction phase or during 6 months' follow-up. There is no relation between bradycardial response to face immersion and frequency of ventricular arrhythmias. PMID- 2897765 TI - Neurotransmission in the hippocampus. PMID- 2897766 TI - [High resolution ultrasound examination in the diagnosis of the undescended testis in the inguinal region]. AB - Twenty-six undescended testes in 22 patients between 1 and 31 years old were evaluated with ultrasonographic examination between October, 1981 and December, 1985. All 22 patients were operated on, and the accuracy of the ultrasonic diagnosis was evaluated in comparison to that of palpation diagnosis. Fourteen of 26 testes could be palpated preoperatively and these were all identified ultrasonographically and surgically. Twelve testes could not be palpated. On these 12 testes, surgical exploration revealed 9 testes in the inguinal region and absence of 3 testes. Ultrasound examination predicted its presence in 5 of 9 testes and its absence in all 3 testes. Both sonography and palpation failed to identify their presence in 4 tests. Thus, sensitivity of ultrasound examination was 82.6%, specificity 100% and accuracy 84.6% retrospectively. We conclude that ultrasound examination is useful in diagnosis of impalpable undescended testes in inguinal region. PMID- 2897767 TI - Human antibody response to human cytomegalovirus-specific DNA-binding proteins. AB - Human antibody responses to human cytomegalovirus (HCMV) specific DNA-binding proteins were studied in serum samples by the Western blot technique. The molecular weights of six DNA-binding proteins found in HCMV-infected cells, ranged from 52kD to 18kD. The sera obtained from patients with acute HCMV infections reacted well with the six HCMV specific DNA-binding proteins. The strongest reactivity was observed with the 52kD and 35kD proteins. The sera from healthy HCMV seropositive donors reacted only with the 52kD DNA-binding protein as visualized in Western blots, but 2 out of 8 sera failed to react with any HCMV specific DNA-binding proteins. PMID- 2897768 TI - Monoclonal antibodies to monkey pox virus: preparation and application. AB - Two fusion experiments with NSO myeloma cells yielded 30 hybrid cell lines which continuously and actively secreted monoclonal antibodies (MoAb) to monkey pox virus. Eight lines appeared to produce antibodies to specific antigenic determinants. The isotype and serologic reactivity of MoAb to monkey pox virus was characterized and the karyotype of several hybridomas determined. An enzyme labelled conjugate has been prepared from MoAb selectively reacting with monkey pox virus. This conjugate allowed the identification of monkey pox virus in the materials from patients. It also helped to determine that an orthopoxvirus isolated from wild squirrel in the Republic of Zaire was monkey pox virus. PMID- 2897769 TI - Immunofluorescent IgG and IgM antibodies in human sera by enterovirus infections. AB - IgG and IgM antibodies to selected enterovirus serotypes (P2, CB 1-5, E2, 4, 20), to prototype collection strains and to fresh isolates were examined by immunofluorescence in paired sera of 11 children and 4 adults in whom enterovirus had been isolated, or a rise of specific antibodies had been proved by neutralization test. One six-month- and one seven-month-old child had antibodies of both classes to the isolated virus strain and to poliovirus only. Children from eight month onwards and adults had antibodies to the majority of enterovirus serotypes tested. Among all enteroviruses tested, heterologous reactions were observed not only with IgG but also with IgM class antibodies. PMID- 2897770 TI - Treatment of rabies in mice and foxes with antiviral compounds. AB - Thirty four chemical compounds were injected into rabies infected mice by intramuscular (i.m.) route. Twenty four compounds such as well known therapeutic agents: amantadine, lipacids, phenol compounds, didemnin-B, procaine, nucleosides analogues (ribavirin, tiazofurin, pyrazofurin) had no effect. Two compounds had a slight effect not justifying to consider them as possible therapeutic agents: selenazofurin and an analogue of ribavirin (RTA). Eight heteropolyanions (HPA), which have a related chemical structure, were efficient providing 100% protection. Nineteen compounds were injected into rabies infected mice by the intracerebral (i.c.) route. Fourteen compounds such as ribavirin, RTA, selenazofurin, tiazofurin and 9 HPA compounds had no effect. Five other HPA compounds (HPA 23-39-46-51-56) were efficient preventing the development of clinical infection in some mice. Whatever was the treatment route, treated surviving mice developed rabies neutralizing antibodies. No proof of viral multiplication was found in their brains. As some HPA compounds did produce a therapeutic effect in mice, two of them HPA 23 and HPA 39 were administered to rabies-infected foxes. In foxes the compounds prolonged the mean survival time and increased the number of survivors. These data suggest that chemotherapy might be worthwhile when vaccination was impossible. PMID- 2897771 TI - Electron microscopic study of developmental stages of Rickettsiella phytoseiuli in Phytoseiulus persimilis Athias-Henriot (Gamasoidea:Phytoseiidae) mites. AB - Rickettsiella phytoseiuli was found in great amounts in all tissues except of the nervous system of adult Phytoseiulus persimilis mites. Six morphologically different stages (dense, intermediate, bacterial, giant, crystal-forming and small dark particles) of R. phytoseiuli were detected. No rickettsiae were seen in the larvae and in phase 1 and 2 nymphae of these mites. PMID- 2897772 TI - De novo initiation of specific cell-mediated immune responsiveness in chickens by transfer factor (specific immunity inducer) obtained from bovine colostrum and milk. AB - Transfer factors (TF) were prepared from colostrum and milk of bovines previously immunized with antigens obtained from Coccidioides immitis, infectious bovine rhinotracheitis virus, or from the viral agents responsible for avian Newcastle disease, laryngotracheitis disease or infectious bursal disease. The ability of bovine TF to transfer specific cell-mediated immune responsiveness to a markedly xenogenic species was studied using specific pathogen free (SPF) and standard commercial (SC) chickens as model recipients. Cell-mediated immune responsiveness was documented using one or more of the following for each antigen (organism) studied: (a) an in vitro chicken leukocyte (heterophil) migration inhibition assay; (b) delayed-wattle reactivity; or (c) protection from clinical disease. Chicken TFs obtained from spleens of immune donors were evaluated in parallel to bovine TF's in selected comparative studies. Bovine TF also referred to as specific immunity inducer (SII), and chicken TF were found to initiate antigen specific cell-mediated immunity de novo in previously non-immune SPF chickens as well as in SC chickens despite the presence of maternally acquired humoral antibody which may serve as a "barrier" to immunization of SC chickens when commercially available vaccines are administered by parenteral routes. Bovine TF's specific for laryngotracheitis virus or infectious bursal disease virus afforded protection equal to that found for commercially available vaccines. Bovine TF's action was rapid (less than a day) and of relatively long duration at least 35 days. PMID- 2897773 TI - Infectivity assay of bovine rotavirus: evaluation of plaque and end-point methods in comparison with immunofluorescent cell assay. AB - Three different methods, namely plaque assay, immunofluorescent cell (IFC) count and end-point dilution (TCID50) were evaluated for quantitative infectivity assay of the cell culture adapted UK strain of bovine rotavirus in secondary calf kidney (CK) cells and BGM cell line. Plaque and IFC count techniques were found equally efficient for infectivity titration of bovine rotavirus. Addition of trypsin into maintenance medium enhanced the sensitivity of the TCID50 method. Both CK and BGM cells served as efficient assay cells for infectivity assay of bovine rotavirus by IFC count and TCID50 methods, whereas, for plaque assay, only CK cells were found suitable. PMID- 2897774 TI - Application of ELISA in the detection of goat pox antigen and antibodies. AB - Enzyme linked immunosorbent assay (ELISA) was standardized for detection of goat pox virus (GPV) antibodies and antigen using live and inactivated antigens and hyperimmune serum (HIS), convalescent, post-vaccinal, as also post-challenge sera. The ELISA was most sensitive in detection of antibody when compared with agar gel precipitation (AGP) and counterimmunoelectrophoresis (CIE) tests. There was no complete correlation between the antibody status of vaccinated goats and protective immunity as animals having detectable seroconversion were also solidly immune to virulent challenge. The application of ELISA in pox infections of goats has been discussed. PMID- 2897775 TI - Diagnosis of endocarditis in acute Q-fever by immunofluorescence serology. AB - The authors compared two groups of 20 patients suffering from Q fever using microimmunofluorescence (micro IF) serology. One group had endocarditis and the other conventional symptoms of acute Q fever but no endocarditis. Determination of the levels of antibodies against the two phases of rickettsiae in each of the three immunoglobulin classes (IgG, IgM and IgA), allowed to determine the type of infection using a single serum sample. Patients having IgA class antiphase I antibodies at a level equal to/or higher than 1:25 as well as those whose antibody levels fulfilled the conditions for the equation (IgG anti-phase I greater than or equal to IgG anti-phase II) + (IgA anti-phase I greater than or equal to IgA anti-phase II) were suffering from endocarditis. The positive predictive value of these tests was 100% and 94.1%, respectively. PMID- 2897776 TI - Terminal sequences of the replicative form of RNA of the Japanese encephalitis virus. AB - The 5' and 3' terminal sequences of the replicative form (RF) of RNA of a flavivirus, the Japanese encephalitis (JE) virus, strain Ja0ArS982, have been determined by in vitro labelling and mobility shift analysis. The plus strand sequence was 5'AGAAGUUUAUCUGUGUGAA...UCUOH3', while the minus strand sequence was 5'AGAUCCUGUGUUCUUCCUCA...UCUOH3'. These sequences were similar to those of West Nile (WN) virus being identical in 12 nucleotides at the 5'terminal of the minus strand, and in the 5'terminal dinucleotides, 5'AG3'. Somewhat more internal hexanucleotides 5'CUGUGU3' are conserved among 3 flaviviruses, the JE, WN, and yellow fever viruses. PMID- 2897777 TI - Tuftsin a natural peptide with antiviral activity--structural basis of its action. AB - The influence of tuftsin--the natural phagocytosis stimulating tetrapeptide and its elongated analogues--on the mortality of encephalomyocarditis virus-infected NMRI mice was investigated. It seems that amino acids elongation in the parent peptide chain does not result in significant increase of antiviral activity of the compounds tested. PMID- 2897778 TI - Transforming activity of crude extract of pseudorabies virus-transformed cells. AB - Crude extract of pseudorabies virus (PRV)-transformed human (H-PR-1) cells induced transformation in human embryonic lung (HEL) cells. When the extract was removed, the acquired cell morphology remained unchanged, but the saturation density of cells was decreased. The transforming effect of the extract was neutralized with anti-PRV IgG. PMID- 2897779 TI - Attempt to cultivate Rickettsiella phytoseiuli in Dermacentor reticulatus ticks: an electron microscopic study. AB - Rickettsiella phytoseiuli occurring in Phytoseiulus persimilis mites was cultivated in Dermacentor reticulatus ticks. Rickettsiella multiplied similarly as in mites exerting all six developmental stages: dense, intermediate, bacterial, giant, crystal-forming and small dark particles. PMID- 2897780 TI - Comparison of bevantolol and atenolol in chronic stable angina. AB - A randomized, double-blind, parallel-group study design was used to compare the antianginal efficacy of bevantolol (200 to 400 mg) and atenolol (50 to 100 mg) each administrated once daily for 8 weeks in 39 patients with chronic stable angina. Assessments were made using 24-hour ambulatory monitoring and treadmill exercise testing performed 22 to 24 hours after the last dose of medication. Both groups were comparable at the end of the placebo phase. In the bevantolol group, exercise time increased from 7.9 +/- 0.7 minutes with placebo to 9.3 +/- 0.7 minutes with bevantolol (mean +/- standard error of the mean) (p less than 0.05). Time to 1 mm ST depression was unaltered. Rest and exercise heart rate decreased (p less than 0.0001 and less than 0.0005, respectively) as did exercise double product (p less than 0.0001). In the atenolol group exercise time increased from 7.1 +/- 0.7 minutes with placebo to 8.2 +/- 0.8 minutes with atenolol (p less than 0.02). Time to 1 mm ST depression increased (p less than 0.005) and rest and exercise heart rate and double product decreased (p less than 0.0001 and less than 0.05, respectively). When within-group differences between placebo and active drug were compared for bevantolol and atenolol, no significant differences were detected. Both drugs were well tolerated and reduced ambulatory heart rate throughout the 24 hours. This study confirms that both bevantolol and atenolol are effective antianginal agents. Bevantolol compares well with atenolol in the treatment of patients with chronic angina, and there was a similar response to exercise testing with the 2 drugs. PMID- 2897781 TI - Transient myocardial ischemia after abrupt withdrawal of antianginal therapy in chronic stable angina. AB - In 47 patients with chronic stable angina and proven coronary artery disease, abrupt withdrawal of beta-adrenoceptor blocking agents either as monotherapy or in combination with calcium antagonists (group 1, n = 25) was compared with abrupt withdrawal of calcium antagonist monotherapy (group 2, n = 22) as regards the occurrence of cardiac events and total ischemic activity detected by ambulatory monitoring. Reinstitution of medical therapy was required in 6 patients (4 in group 1 and 2 in group 2). Ambulatory monitoring was initiated for 36 hours on 3 occasions: before withdrawal, and again 2 and 5 days after withdrawal. The first 2 monitorings were performed in the hospital and the last during daily activity. In group 1, the frequency of total ischemia increased by 64 and 148% from monitoring occasions 1 to 2 and 1 to 3, respectively (p less than 0.01), and silent ischemia increased by 100 and 129%, respectively (p less than 0.01). However, no significant change in transient myocardial ischemia was noted in group 2. Heart rate at onset of ischemia increased significantly in group 1 (p less than 0.01), in contrast to group 2 which had significant increases only in out-of-hospital values (p less than 0.05). These results indicate that a rebound increase in ischemic activity (mainly silent) occurs after abrupt withdrawal of beta-receptor blockade in patients with chronic stable angina. This increase in ischemic activity may be caused by increased myocardial oxygen demand. PMID- 2897782 TI - Human alpha-linolenic acid deficiency. PMID- 2897783 TI - Current status of maintenance therapy in peptic ulcer disease. The ACG Committee on FDA-Related Matters. PMID- 2897784 TI - Nizatidine and ranitidine in the short-term treatment of duodenal ulcer: a cooperative double-blind study of once-daily bedtime administration. AB - The aim of the present study was to assess the clinical efficacy and safety of a new H2-antagonist, nizatidine (N), administered as a single bedtime dose of 300 mg, compared with ranitidine (R) at the same dosage, in the short-term treatment of duodenal ulcer. One hundred forty one patients were included in the study: 70 were treated with N and 71 with R. During the study, three patients were withdrawn for unwanted effects not related to the treatment, and therefore, 69 patients per group were studied. After 4 wk of treatment, 58 patients treated with N (84.1%) and 55 in the group treated with R (77.5%), showed complete endoscopic ulcer healing (p greater than 0.5). The corresponding figure after 8 wk of therapy was 64 (94.2%) and 65 (94.2%) (p greater than 0.5). A similar effect on pain relief was observed: 42% of patients in both groups became asymptomatic after 4 wk. After 8 wk, the percentage rose to 84.2% in the group treated with N and 87.0% in the R group (p greater than 0.5). In both groups, only minor side effects occurred, not requiring drug discontinuation. These data show that nizatidine in a single bedtime dose of 300 mg is as effective and safe as ranitidine at the same dosage, and represents therefore a valid alternative to the usual H2-antagonists. PMID- 2897785 TI - Role of gluconeogenesis from amino acids in determining fasting and absorptive levels of plasma ammonia in cirrhosis. AB - The aim of this study was to evaluate the contribution of gluconeogenesis from amino acids in the development of fasting and absorptive hyperammonemia in cirrhosis. Somatostatin (SRIF), which is known to inhibit the hepatic disposal of gluconeogenic amino acids, was administered in a continuous infusion (500 micrograms/h) for 90 min before and 5 h after a protein meal (240 g of meat) in 11 overnight fasting patients. Plasma glucagon, insulin, gluconeogenic amino acids (GAA: alanine, serine, glycine, and threonine) and ammonia (NH3) were evaluated before the infusion, immediately before, and at 1, 3, and 5 h after the meal. As control study, the same protocol was randomly repeated in a different day with saline infusion. During the latter, a direct correlation was found between fasting glucagon and ammonia (r = 0.68; p less than 0.05). Fasting glucagon, insulin, and NH3 did not change, whereas alanine (p less than 0.05) and the GAA sum decreased (p less than 0.01). When SRIF was infused, fasting glucagon (p less than 0.05), insulin (p less than 0.05), and NH3 (p less than 0.05) decreased. Alanine did not change, and GAA sum increased (p less than 0.02). No correlations were found by plotting changes in glucagon or GAA sum and NH3. After the meal, SRIF infusion abolished the plasma response of glucagon and markedly reduced that of insulin, so that their area under the curve (AUC0-5) were reduced (p less than 0.005, for both), with respect to control study. Moreover, the AUC0 5 of alanine (p less than 0.005) and GAA sum (p less than 0.005) were increased, suggesting a reduced disposal of these compounds. In spite of this, the meal induced early increase and the AUC0-5 of plasma NH3 observed during SRIF and saline infusion did not differ. Our results do not confirm the importance of gluconeogenesis from alpha-amino-nitrogens in determining the fasting ammonemia of cirrhosis, and suggest that this metabolic pathway does not significantly influence the protein meal-induced exacerbation of plasma ammonia. PMID- 2897786 TI - Linkage disequilibrium between cystic fibrosis and linked DNA polymorphisms in Italian families: a collaborative study. AB - The locus D7S23 includes a CpG-enriched methylation-free island that maps midway between the markers J3.11 and met and is genetically very close to the mutation causing cystic fibrosis (CF). We have studied the linkage disequilibrium between four polymorphic markers from this locus (KM.19, CS.7, XV-2c, and PT-3) and the CF mutation (CF) in 127 Italian families. Strong linkage disequilibrium is found between KM.19, CS.7, and CF, and weaker but significant disequilibrium is found between XV-2c, PT-3, and CF. The disequilibrium between markers and CF for the Italian population provides additional information on the origin and homogeneity of the CF defect. This panel of probes is sufficiently informative to permit accurate prenatal diagnosis of CF in most families with an affected person, and the disequilibrium also allows indirect carrier detection/exclusion in some cases. PMID- 2897787 TI - Determination of the spectrum of beta-thalassemia genes in Spain by use of dot blot analysis of amplified beta-globin DNA. AB - We have delineated the molecular lesions causing beta-thalassemia in Spain, a country that has witnessed the passage of different Mediterranean populations over the centuries, in order to evaluate the extent of heterogeneity of these mutations and to make possible simplified prenatal diagnosis of the disorder in that country. The use of the polymerase chain-reaction (PCR) technique to preferentially amplify beta-globin DNA sequences that contain the most frequent beta-thalassemia mutations in Mediterraneans enabled us to rapidly analyze 58 beta-thalassemia alleles in a dot-blot format either by hybridization with allele specific radiolabeled oligonucleotide probes or by direct sequence analysis of the amplification product. The Spanish population carries seven different beta thalassemia mutations; the nonsense codon 39 is predominant (64%), whereas the IVS1 position 110 mutation, the most common cause of beta-thalassemia in the eastern part of the Mediterranean basin, is underrepresented (8.5%). The IVS1 mutation at position 6 accounts for 15% of the defects and leads to a more severe form of beta+-thalassemia than originally described in most of the patients we studied. In this study, we demonstrate further the usefulness of the dot-blot hybridization of PCR-amplified genomic DNA in both rapid population surveys and prenatal diagnosis of beta-thalassemia. PMID- 2897788 TI - Amelioration of vincristine neurotoxicity by glutamic acid. AB - Neurotoxicity is the principal limiting side effect of the widely used antitumor agent, vincristine. Following evaluation of glutamic acid as a potential modifier of vincristine toxicity in preclinical studies in mice and a preliminary clinical trial, a prospective, double-blind, placebo-controlled, randomized trial was conducted by the Piedmont Oncology Association. Of 87 patients entered into the study, 84 were evaluable, including 42 patients who were randomly assigned to receive vincristine 1.0 mg/m2 weekly for six doses and 42 patients who were assigned to receive glutamic acid 500 mg orally three times daily plus vincristine. The following neurotoxic signs and symptoms were evaluated before each dose of vincristine: reflex changes, paresthesias, constipation, strength, and mental changes. Loss of the Achilles tendon reflex, an objective parameter, was noted in 19 percent of patients receiving glutamic acid and 42 percent of control subjects (p = 0.03). Development of moderate to severe paresthesias, a subjective parameter, occurred in 19 percent of the glutamic acid group and 36 percent of the placebo group (p = 0.09). Overall moderate neurotoxicity (6 units or more), determined by adding the grade of each neurotoxic parameter for the weekly clinic visit in which maximum neurotoxicity occurred, was observed in 21 percent of patients receiving glutamic acid and 43 percent of those in the control group (p = 0.04). Hematologic and gastrointestinal side effects occurred with similar frequency in the two groups. The administration of glutamic acid has decreased vincristine-induced neurotoxicity without any attendant side effects. PMID- 2897789 TI - Benzodiazepine withdrawal: overview and implications for the treatment of anxiety. AB - The authors critically review 20 reports (studies and large case series) detailing the nature, severity, and variability of benzodiazepine withdrawal syndromes. Factors affecting the frequency and intensity of withdrawal are identified, and methodologic problems limiting the generalizability of certain findings are pointed out. Treatment approaches for minimizing withdrawal are reviewed, and implications for the problem of long-term benzodiazepine use and dependence are discussed. PMID- 2897790 TI - Treatment response with bilateral mixed deafness and facial palsy in polyarteritis nodosa. PMID- 2897791 TI - Systemic necrotizing vasculitis causing bone necrosis. PMID- 2897792 TI - Diagnosis of classical steroid 21-hydroxylase deficiency using an HLA-B locus specific DNA-probe. AB - The HLA-B and steroid 21-hydroxylase loci are known to be closely linked. Restriction fragment length polymorphisms seen after digestion of genomic DNA with MspI and TaqI with the HLA-B locus-specific DNA-probe, pHLA-1.1, were examined in 7 nuclear families with classical steroid 21-hydroxylase deficiency. In each family 2 polymorphic hybridizing bands (corresponding to the 2 HLA-B genes) were seen. In all families, TaqI-generated polymorphisms allowed for identification of children previously shown on clinical and biochemical criteria to be affected by 21-hydroxylase deficiency from their unaffected sibs. The results were in complete agreement with the clinical diagnoses. Among the unaffected children, carriers could be distinguished from non-carriers in all cases by TaqI polymorphisms. MspI-generated polymorphisms allowed for full identification of genotypes in 5 families. In one family, MspI-generated polymorphisms could be used to identify affected from unaffected children, but could not distinguish between carriers and non-carriers. In another family, no identification of genotypes was possible by MspI-generated polymorphisms alone. The HLA-B locus-specific DNA-probe, pHLA-1.1, can be used for diagnosis and genotyping of individuals from families with 21-hydroxylase deficiency. This technique can be used as an alternative to HLA-serotyping, or in situations where HLA-serotyping is technically difficult, for example in chorionic villus samples. PMID- 2897793 TI - Direct method for prenatal diagnosis and carrier detection in Duchenne/Becker muscular dystrophy using the entire dystrophin cDNA. AB - DNA sequence polymorphisms (RFLPs) have been widely used as genetic markers for identification of the X chromosome that carries the mutation for Duchenne muscular dystrophy (DMD) in affected families, but serious limitations and pitfalls are associated with this approach [Darras et al., 1987]. The complementary DNA (cDNA) of the DMD gene has recently been isolated and shown to detect partial gene deletions in a large proportion of patients [Koenig et al., 1987]. Two prenatal studies are presented to illustrate how the unambiguous identification of deletion mutations by cDNA probes permits direct DNA-based diagnoses with high accuracy and in otherwise uninformative families. In a single proband family, DNA marker analysis had determined that the Xp21 chromosomal region present in the affected male was also carried by a male fetus in a subsequent pregnancy. Analysis of this family's DNA with probes covering the entire 14 kb cDNA revealed a small deletion in the affected male that was not present in the fetus nor in the mother. In the second family the fetus was a female deletion carrier identified by comparing intensities of restriction fragments. Since 1/3 of all DMD patients are thought to result from new mutations and most families have only single affected males, the cloned cDNA probes now available are likely to revolutionize DNA-based diagnostic studies in this disorder. More reliable, more rapid and less expensive than linkage studies with DNA polymorphisms, this method will be informative in the more than 50% of DMD/BMD cases that have deletion mutations. PMID- 2897794 TI - Relieving pain. An analgesic guide. PMID- 2897795 TI - Modulation of receptor-mediated gonadotropin action in rat testes by dietary fat. AB - The effect of feeding diets enriched with 18:2 omega 6, 18:3 omega 3, or saturated fatty acids on lipid composition and receptor-mediated action of luteinizing hormone/human chorionic gonadotropin (LH/hCG) in rat testicular plasma membranes was investigated. Linoleic and alpha-linolenic acid treatments reduced total phospholipid and cholesterol content of the testicular plasma membrane and altered membrane phospholipid composition. Change in phospholipid and cholesterol content after feeding the polyunsaturated fats decreased cholesterol to phospholipid ratios and binding capacity of the LH/hCG receptor in the testicular plasma membrane. LH-stimulated adenylate cyclase activity was decreased in animals fed the linolenic acid-rich diet. NaF-stimulated adenylate cyclase activity was decreased in animals fed diets high in either polyunsaturated fatty acid. Decreased plasma membrane LH/hCG receptor content was associated with decreased testosterone production in Leydig cells in response to LH in the linolenic acid-fed group. It is suggested that change in cholesterol-to phospholipid ratios alters the physical properties of testicular plasma membranes in a manner that influences accessibility of LH/hCG receptors in testicular tissue. PMID- 2897796 TI - Modulatory effect of glucose on VIP-induced gastric somatostatin release. AB - The present study was designed to examine the effect of increasing perfusate glucose concentrations on vasoactive intestinal peptide (VIP)-induced somatostatin (SLI) release from the isolated rat stomach. The stomach of overnight-fasted rats was perfused with Krebs-Ringer buffer containing 100, 150, or 200 mg/dl glucose, respectively. VIP was administered at 10(-12), 10(-11), 10( 9), and 10(-8) M. At a normal glucose concentration of 100 mg/dl, VIP at doses of 10(-12), 10(-11), and 10(-9) M elicited a small inhibitory effect on SLI release by 200-300 pg/min (P less than 0.01). As reported previously at 10(-8) M, VIP stimulated gastric SLI secretion by 500 pg/min (P less than 0.01). Increasing perfusate glucose to 150 mg/dl resulted in a stimulation of SLI release by all four concentrations of VIP with a maximal effect at 10(-9) M. During 200 mg/dl glucose, VIP had no effect in concentrations below 10(-9) M, and only the two highest doses (10(-9) and 10(-8) M) stimulated SLI release significantly. In the absence of VIP, glucose had no effect on gastric SLI release. In conclusion, the present data demonstrate for the first time that at normal glucose levels VIP has not only stimulatory but also inhibitory effects on gastric SLI, and second, a modest elevation of glucose has a modulatory effect on gastric D-cell function. PMID- 2897797 TI - CNS blockade of acoustic stress-induced gastric motor inhibition by kappa-opiate agonists in dogs. AB - The influence of the kappa-opioid substances dynorphin-(1-13), ethylketocyclazocine (EKC), and U 50488 and mu-opioid substance [D-Ala2-N-Me, p nitro-Phe4-Gly5-ol]enkephalin (DAGO) on gastric motor inhibition induced by acoustic stress (AS) was investigated in fasted dogs with strain-gauge transducers chronically implanted on the antrum and proximal jejunum. AS induced by 1 h of music (80-90 dB) was delivered through earphones. Starting 40-50 min after the last migrating motor complex (MMC), AS delayed by 114% the occurrence of the next gastric MMC, whereas intestinal motility was unaffected. During AS plasma cortisol increased (P less than 0.05) by 215%, 15 min after the beginning of noise and reached a peak at 30 min. When administered intracerebroventricularly at doses higher than 20 ng/kg, dynorphin abolished the AS-induced lengthening of the gastric MMC cycle. Similar blockade was observed for EKC and U 50488 at doses of 10 and/or 20 ng/kg, but DAGO was unable to affect the AS-induced gastric inhibition at any dosage tested (20-200 ng/kg icv). At doses effective against AS-induced hypomotility, both dynorphin-(1-13) and EKC reduced significantly (P less than or equal to 0.05) the associated maximal increase in plasma cortisol level. Plasma cortisol was unmodified by intracerebroventricular administration of DAGO. None of the agonists affected basal plasma cortisol levels or the increase (0-90 min) in response to intravenous adrenocorticotropic hormone (ACTH, 5 IU). Both EKC (50 ng/kg) and U 50488 (20 ng/kg) were unable to antagonize the inhibitory effect of ovine corticotropin-releasing factor (CRF, 100 ng/kg icv).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897798 TI - Sources of calcium for contraction of distal circular muscle or taenia coli in the rabbit. AB - Studies were performed on proximal taenia coli and distal circular muscle from the rabbit to determine if the source of Ca2+ required for bethanechol stimulation of contraction was similar after permeabilizing the tissues with saponin. The EC50 for Ca2+ stimulation of contraction was pCa 6.1 +/- 0.1 for both tissues. The peak response occurred at pCa 4.5. The addition of 1 microM calmodulin did not alter the Ca2+ EC50 or the peak response. Caffeine (20 mM) stimulated contraction of both taenia coli and distal circular muscle. The caffeine-stimulated contractile response was threefold greater in the taenia than in the distal circular muscle (P less than 0.05). Perfusion of thin strips of colonic muscle with buffer, containing 10(-7) M Ca2+, reduced the amplitude of bethanechol-stimulated contraction. The perfusion time to reduce the contraction by 50% was greater in the proximal muscle (2.4 +/- 0.1 min) than in the distal muscle (1.1 +/- 0.5 min) (P less than 0.001). These data suggest that 1) the intracellular Ca2+ concentration necessary for contraction is similar in the proximal and distal colon and 2) the intracellular Ca2+ stores appear to be greater in proximal taenia coli compared with distal circular muscle. PMID- 2897799 TI - Role of glucagon in cholecystokinin-stimulated bile flow in dogs. AB - Although many choleretic agents are known, their physiological roles and interrelationships in increasing bile flow remain largely undetermined. Exogenous cholecystokinin (CCK), glucagon, and insulin are stimulants of hepatic bile flow in animals and humans. Of possible importance in the choleresis produced by CCK is the stimulation by exogenous CCK of glucagon and insulin release from the pancreas. This research evaluates the role of glucagon and insulin in the choleresis produced by CCK. Dogs with chronic biliary and gastric fistulas were used. The synthetic octapeptide of CCK (CCK-8) administered in increasing doses produced progressive increases in bile volume, bile bicarbonate secretion, and bile chloride concentration and output. The choleresis produced by CCK-8 was qualitatively similar to that produced by intravenous glucagon. CCK-8 administration in increasing doses produced progressive increases in plasma glucagon. When bile flow changes during CCK-8 administration were correlated with changes in plasma glucagon, significant correlation existed. CCK-8 significantly increased serum insulin concentration only at the highest dose of CCK-8 administered. Somatostatin is an inhibitor of hormone release. Administration of somatostatin, along with CCK-8, inhibited the choleresis and the increased plasma glucagon produced by CCK-8 administration alone. During acute experiments in anesthetized dogs, the pancreas and stomach were removed to eliminate endogenous glucagon and insulin release. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897800 TI - Developmental regulation of rat intrinsic factor mRNA. AB - Using a full-length rat intrinsic factor (IF) cDNA clone, we have examined gene expression of IF in selected tissues from the adult rat and during postnatal development in the rat stomach. IF mRNA was expressed only in the rat stomach, and in situ hybridization revealed that the expression was limited to the chief cells at the base of the oxyntic glands. IF mRNA concentration in the stomach increased with postnatal age and reached a peak at the 30th day. Postnatally the amount of IF mRNA hybridized increased in both individual cells and in total number of cells. Administration of cortisol to, or adrenalectomy of, rats between 5 and 12 days of age resulted in increase or decrease of IF mRNA levels, respectively. Other hormones tested (pentagastrin, thyroxine, and triiodothyronine) had no significant effect. During the suckling period, IF bound well to the ileal receptor, despite lower than adult levels of activity and different glycosylation, as assessed by binding to concanavalin A-Sepharose beads. These results show that developmental expression of IF activity in rat is closely related to the expression of its mRNA and that corticosteroids play an important role in such an expression. PMID- 2897801 TI - [Beta-adrenomimetics in current obstetrics]. PMID- 2897802 TI - Further studies on the neurochemical mechanisms mediating differences in ethanol sensitivity in LS and SS mice. AB - Long-sleep (LS) and short-sleep (SS) lines of mice were selectively bred for differences in CNS sensitivity to ethanol with LS mice exhibiting much greater sensitivity to hypnotic doses of ethanol (4.0-4.5 g/kg) than SS mice. The influence of peripheral and central catecholamine neuronal systems on ethanol sensitivity (sleep time) in LS and SS mice was examined following administration of reserpine, alpha-methyl-p-tyrosine and 6-hydroxydopamine. Ten days after a single dose of reserpine, tyrosine hydroxylase activity was increased in the brain and adrenal gland of LS mice but only in the brain of SS mice relative to untreated mice. Brain catecholamine levels in the reserpine-treated mice were 25 50% lower in both LS and SS mice compared to levels in untreated mice. These changes were associated with a 41% reduction in LS sleep time, but a 90% increase in SS sleep time. SS mice were also more susceptible to the lethal effects of reserpine. The increased mortality of SS mice may relate to a greater degree of reserpine-induced hypothermia and a slower rate of recovery of brain catecholamine levels. Neonatal LS and SS mice treated with 6-hydroxydopamine exhibited increased levels of catecholamines in the locus ceruleus, decreased levels in the cerebellum and unchanged levels in the hypothalamus at 60 days of age. These changes were associated with a modest decrease (10%) in LS sleep time and a marked increase (200%) in SS sleep time. alpha-Methyl-p-tyrosine decreased brain catecholamine levels of both lines by 30-50% while LS sleep times were unchanged and SS sleep times were increased by 45%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897803 TI - Cardiac mitochondrial abnormalities in a mouse model of the fetal alcohol syndrome. AB - Mitochondrial enzymes and respiration were studied in the hearts of mice exposed to ethanol in utero from gestational Day 8 to parturition. This treatment had previously been shown by electron microscopy to result in myofibril loss and mitochondrial abnormalities. Ethanol was administered to pregnant mice by a liquid diet paradigm and pair-fed dams were used as controls. Ethanol exposure in utero reduced the activities of two mitochondrial inner membrane enzymes, cytochrome c oxidase and succinate dehydrogenase, in the hearts of perinatal mice. Secondly, mitochondrial respiration under both State 3 and 4 conditions with a NAD-linked substrate was depressed in the hearts obtained from the ethanol exposed fetal mice. However, when a flavin-linked substrate was used, State 3 (ADP-stimulated) but not State 4 respiration was depressed. This study illustrates that in utero exposure to ethanol is deleterious to the functioning of cardiac mitochondria in newborn mice, which in turn could contribute to the development of the heart pathologies present in the Fetal Alcohol Syndrome. PMID- 2897805 TI - Anxiety and informed consent. Does anxiety influence consent for inclusion in a study of anxiolytic premedication? AB - Forty-three consecutive patients were interviewed on the eve of elective gynaecological surgery to determine the effect of anxiety on the granting of informed consent to participate in an hypothetical study. Anxiety was assessed using the Spielberger state-trait anxiety inventory and 10-cm linear analogue scale. A standardised explanation of an hypothetical premedication study was given and the patients' consent requested. Results were grouped for those who granted (n = 33) and those who withheld (n = 10) consent: anxiety scores for the latter were significantly higher (p less than 0.01). It is concluded that patients with high pre-operative anxiety levels are more likely to withhold consent for inclusion in premedication studies than are those who are less anxious. Seeking informed consent would introduce bias into studies of anxiolytic premedication. PMID- 2897804 TI - Efficacy of an oral antihistamine, astemizole, as compared to a nasal steroid spray in hay fever. AB - The efficacy and side effects of the oral H1-antihistamine, astemizole, were compared with those of nasal beclomethasone in 158 adult birch-pollen allergic hay fever patients. 148 patients completed the 5-week, controlled trial which took place in Stockholm, May 1986, during the birch pollen season. Daily pollen counts were found to be at a rather low level throughout the study period. The effect and tolerability of both drugs were found to be excellent, although beclomethasone reduced nasal symptoms (sneezing, rhinorrhoea, blocked nose) significantly more effectively than astemizole. Eye symptoms were mild and equal in both groups. The results indicate that oral astemizole is an effective non sedating antihistamine, though less so than nasal beclomethasone, in the treatment of nasal hay fever symptoms. PMID- 2897806 TI - Intranasal sufentanil for pre-operative sedation. AB - Sufentanil, a short-acting and potent narcotic agent, was studied as a premedicant administered by the nasal route. A total dose of 5 micrograms appeared to be too low, while either 10 or 20 micrograms was very effective in producing sedation. Side effects were minor. There appeared to be no differences between nose drops and spray. In a further study, sufentanil nose drops were compared with saline 0.9% in a double-blind fashion. Sedation of rapid onset but of limited duration was observed in the majority of patients who received sufentanil. PMID- 2897807 TI - Pain during injection of vecuronium. PMID- 2897808 TI - Volatile anesthetics attenuate sympathomimetic actions on the guinea pig SA node. AB - The authors examined and compared the direct effects of three volatile anesthetic agents and three sympathomimetic agonists on transmembrane action potential (AP) characteristics and automaticity of sinoatrial (SA) nodal pacemaker cells. SA nodal tissue was isolated from guinea pig hearts and suffused in vitro with oxygenated Krebs-Ringer solution. Electrophysiologic variables measured were: amplitude of the AP, slopes of phase 4 and of phase 0 of the AP, AP duration, and spontaneous sinus rate. The authors found that 1 and 2 MAC equivalents of each anesthetic, 0.8 and 1.6 vol % halothane, 1.4 and 2.8 vol % isoflurane, and 1.7 and 3.4 vol % enflurane similarly depressed the slopes of phase 4 and 0 of the AP, prolonged AP duration, and slowed the sinus rate at 1 and 2 MAC equivalents. Isoproterenol, 0.25 microM, and epinephrine, 50 microM, maximally enhanced the slopes of phase 4 and 0 of the AP, shortened AP duration, and increased the sinus rate, but phenylephrine, 50 microM, only moderately increased the slope of phase 4 and the sinus rate. Each of the three anesthetics caused baseline depressions of phase 4 and phase 0 slopes and of automaticity of SA nodal cells; the fall in sinus rate was counteracted, but was not reversed maximally by increasing the concentrations of isoproterenol, epinephrine, or phenylephrine. Regression analyses of linearly transformed data showed that each of the anesthetics similarly depressed basal sinus rate, so that changes in rate produced with isoproterenol and epinephrine were not different from those observed with beta agonists in the absence of anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897809 TI - Synergistic interaction of alpha 1- and beta-adrenoceptor agonists on induction arrhythmias during halothane anesthesia in dogs. AB - The authors investigated the role of alpha 1- and beta-adrenoceptors on the induction of arrhythmias during halothane anesthesia in the dog. The arrhythmogenic doses (ADs) of various combinations of alpha 1- and beta adrenoceptor agonists were determined in dogs (N = 105) during halothane anesthesia. Isoproterenol (ISP) and phenylephrine (PHE) administered separately failed to induce arrhythmias in doses up to 4 micrograms/kg and 200 micrograms/kg, respectively. The interaction between ISP and PHE in inducing arrhythmias showed typical hyperbolic isoboles. At a systolic pressure of 140 mmHg, the AD of ISP in the presence of PHE was significantly lower than that in the presence of angiotensin II (ANG II). At a systolic pressure of 150, 160, 170, or 180 mmHg, there was no significant difference between the AD of ISP in the presence of PHE and that in the presence of ANG II. Increasing heart rate by electrical pacing did not replace ISP in the arrhythmogenic interaction between ISP and PHE. The results indicate that both alpha 1- and beta-adrenoceptor agonists are important for producing arrhythmias during halothane anesthesia, and that these agonists synergistically interact on the heart by different mechanisms. PMID- 2897810 TI - Altered hemodynamic response to dobutamine in relation to the degree of preoperative beta-adrenoceptor blockade. AB - The relationship between the extent of preoperative beta-adrenoceptor blockade and the hemodynamic properties of dobutamine was investigated in patients scheduled for elective myocardial revascularization during isoflurane-nitrous oxide anesthesia. Twenty patients had been treated with beta-adrenoceptor blocking drugs for at least 4 weeks before the study; 11 unblocked patients served as control group. The extent of clinical beta-adrenoceptor blockade was quantified using the isoproterenol sensitivity test. The dose of isoproterenol required to increase heart rate by 25 beats/min was defined as the CD25 (chronotropic dose 25), representing the degree of beta-adrenoceptor blockade. Geometric mean CD25/70 kg was 3.8 micrograms in the control group, and 24.5 micrograms in the patients receiving beta-adrenoceptor blocking drugs. The authors found a significant inverse relationship between CD25 values and changes in cardiac index in response to three dobutamine infusion rates (1.0, 2.0, and 4.0 micrograms.kg-1.min-1), the correlation coefficients being -0.78, -0.79, and 0.82, respectively. Compared to unblocked patients, almost no change, or even a decrease, of the cardiac index was observed at higher degrees of clinical beta adrenoceptor blockade. Moreover, there was a significant linear correlation (r = 0.66 - 0.75) between CD25 values and the effects of dobutamine on systemic vascular resistance index (SVRI), i.e., SVRI decreased in control patients, but increased in patients with high degrees of preoperative beta-adrenoceptor blockade. This unmasked vasocontrictive response to dobutamine was observed despite the fact that the majority of our patients had received cardioselective adrenergic blocking drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897811 TI - Relative analgesic potency of epidural fentanyl, alfentanil, and morphine in treatment of postoperative pain. PMID- 2897812 TI - Bevantolol vs propranolol: a double-blind controlled trial in essential hypertension. AB - Bevantolol is a novel beta 1-selective beta-adrenoceptor antagonist. The Study Group evaluated its therapeutic utility (100-300 mg bid) compared with propranolol (80-240 mg bid) in 266 patients with mild to moderate essential hypertension (WHO Grades I and II, sitting diastolic blood pressure (DBP) greater than or equal to 95 mmHg). There was no difference in their antihypertensive efficacy over six months, 77% being controlled (DBP less than or equal to 90 mmHg) on bevantolol and 81% on propranolol. Hydrochlorothiazide 25-50 mg bid added later improved BP control in those incompletely controlled on bevantolol monotherapy. Both beta-adrenoceptor antagonists also reduced intraocular pressure. Bevantolol caused significantly fewer adverse effects than propranolol with many fewer withdrawals during long-term therapy. This unique clinical pharmacologic profile of bevantolol enhances its therapeutic usefulness and may relate to alpha-adrenoceptor antagonist activity, as well as to its beta 1 selectivity. PMID- 2897813 TI - Hemodynamic effects of nebivolol in men: comparison of radionuclide angiocardiography with systolic time intervals. AB - In a subacute experiment the authors studied the effects of a fourteen -day treatment with nebivolol, 5 mg once a day, in 10 healthy male volunteers with a mean age of thirty-one, twenty-five to thirty-nine years, by comparing the results of the resting ratio of the preejection period (PEP) to the left ventricular ejection time (LVET), as measured by systolic time intervals (STI), with the results obtained by equilibrium radionuclide angiocardiography (ERNA), using technetium 99m-labeled autologous red blood cells as a marker. A submaximal treadmill exercise test performed before and during treatment demonstrated that nebivolol significantly (p less than 0.01) reduced peak exercise heart rate and systolic blood pressure from a mean value of 158 +/- 5.4 bpm to 131 +/- 4.3 bpm and from 171 +/- 4.9 mmHg to 144 +/- 4.5 mmHg respectively. The data from the STI and ERNA were calculated and analyzed independently by two observers. A highly significant (r = 0.8182, p = 0.0038) correlation was found between the changes of stroke volume (SV) and PEPc/LVETc during treatment with nebivolol. Furthermore end-diastolic volume significantly(p = 0.03) increased from a mean value of 177 +/- 10.1 ml to 198 +/- 6 ml and stroke volume significantly (p = 0.01) increased from 120 +/- 6.8 ml to 136 +/- 6.3 ml. Systemic vascular resistance tended to decrease from a mean value of 11.4 +/- 1.28 units to 10.6 +/- 1.10 units. No changes could be observed either in ejection fraction or in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897814 TI - Identification of bovine kappa-casein genotypes at the DNA level. AB - By using a bovine kappa-Cn cDNA as probe and the PstI endonuclease we demonstrate that the DNA restriction patterns of kappa-Cn AA and kappa-Cn BB cows are different. Besides two invariant fragments (about 6.8kb and 1.1kb) the former shows two fragments of about 4.3 kb and 0.3 kb and the latter one fragment of about 4.6 kb. kappa-Cn AB cows show intermediate pattern. Therefore, it is possible to determine the bovine kappa-Cn genotypes even in absence of gene product. PMID- 2897815 TI - Mechanisms of altered hormone and neurotransmitter action during aging: the role of impaired calcium mobilization. AB - Age-related changes in hormone and neurotransmitter regulation of physiological functions result from various mechanistic alterations. In many cases changes in the receptors for these agents appear to be closely linked to altered responsiveness. In other instances, receptors are unaffected by aging, and various post-receptor changes result in functional deterioration. Examples of the latter situation include stimulation of cyclic AMP production and high-affinity association of steroid receptor-hormone complexes with nuclear acceptor sites in various cell and tissue types. One of the most noteworthy post-receptor changes appears to be an impaired ability to stimulate calcium mobilization in many aged systems resulting in reductions in various biological responses. Although the processes which govern regulation of calcium fluxes vary with cell type, many such dysfunctions can be at least partially reversed if sufficient calcium can be transported to appropriate cellular sites. Thus, elucidation of the molecular mechanisms involved in impaired calcium mobilization may provide the basis for new therapeutic strategies. PMID- 2897816 TI - Immunoregulation in aging. PMID- 2897817 TI - Neurohumoral mechanisms of the formation of antitumoral activity. PMID- 2897818 TI - The relationship of receptor reserve and agonist efficacy to the sensitivity of alpha-adrenoceptor-mediated vasopressor responses to inhibition by calcium channel antagonists. PMID- 2897819 TI - Calcium antagonists for angina pectoris. AB - Angina presents itself to us as a continuous spectrum of ischemic syndromes. The disease is multifactorial, and within the same patient different pathophysiological mechanisms may occur at different times and in succession. Several factors may be causative at a particular moment of the disease process and the very next moment a different mechanism may prevail or spontaneous improvement may occur. Among these are stable atheroma with episodic increased vasomotor tone, fissured plaques with intraluminal and/or intraintimal thrombus, thrombocyte aggregation in greater than 70% intraluminal narrowing from ulcerated plaques, as well as frank spasm of vessels without major atherosclerosis. Consequently, there will never be one therapy for every case of (un)stable angina nor will there ever be a best therapy for all. Rather, a stepped approach appears the most likely to be successful. This begins with bed rest and requires vasodilator therapy with nitrates and/or Ca2+ antagonists and beta blockade. If this triple therapy does not "cool" the symptoms within 6-12 hours, semiurgent arteriography is indicated. Depending on the pathophysiology found, thrombolytic therapy with streptokinase or tissue plasminogen activator, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) must be carried out early. Heparin in the short term and aspirin in the long term protect best against late complications. The moment is now here when infarction or death after an attack of angina pectoris should be rare. PMID- 2897820 TI - A distally based median plantar flap. AB - The first metatarsophalangeal joint area is a very difficult one to reconstruct, needing skin that is thick, sensitive, and resistant to friction. Although the medial plantar island flap was initially described to resurface heel defects, we have used this flap as a cross-foot flap to recover the first metatarsophalangeal joint area. Its use has always required a second surgical procedure. To overcome this inconvenience, we describe the use of a flap based on the principle of reversing the direction of blood flow in a distal vascular pedicle to restore a defect of the anteromedial aspect of the foot. Good functional and aesthetic results were obtained. PMID- 2897821 TI - [Distribution of alanine and aspartate aminotransferases, gamma glutamyltransferase, lactate dehydrogenase, alkaline phosphatases and creatine kinase in the main organs of adult goats and kids]. AB - In adult ewes, the distribution of enzymes in the liver, kidney, spleen, pancreas, muscle, lung and myocardium was very similar to that in cows or sheep: aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), lactate dehydrogenase (LDH) and creatine kinase (CK) were mainly in skeletal muscles and the myocardium, while gamma-glutamyl transferase (GGT) and alkaline phosphatases (PAL) predominated in the kidneys. Age-related changes of tissue enzyme patterns were dominated by a dramatic decrease of liver ALAT in adults whereas this enzyme was liver-specific in one month old animals; a decrease of muscle LDH and CK, and an increase of kidney GGT and ALP were also observed in adults. PMID- 2897822 TI - Cortical somatostatin, neuropeptide Y, and NADPH diaphorase neurons: normal anatomy and alterations in Alzheimer's disease. AB - Somatostatin and neuropeptide Y are two neuropeptides that are of particular interest in Alzheimer's disease because they are reported to be depleted in cerebral cortex. In the present study we examined somatostatin, neuropeptide Y, and nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase neurons in nine cortical regions in both normal and Alzheimer's disease brains. These three neurochemical markers show a high degree of co-localization (greater than 90%) in nonpyramidal neurons that are primarily distributed in cortical layers II-III, V VI, and, most prominently, in infracortical white matter. The highest cell density was in temporal and parietal association cortex. The major morphological abnormality in Alzheimer's disease brains was a marked pruning and distortion of fiber plexuses with an apparent reduction in fiber density. In contrast, perikaryal density was preserved except for a reduction in parietal association cortex. Approximately 10 to 15% of senile plaques in the inferior temporal gyrus contained abnormal neurites. Additional abnormal collections of neurites without plaque cores were frequently found in layers II-III and V-VI. Neuropeptide Y and somatostatin were co-localized in abnormal neurites, suggesting an origin from local intrinsic neurons in which the two peptides are co-localized. Double immunofluorescence staining for both tau protein, a major antigenic component of paired helical filaments, and either somatostatin or neuropeptide Y showed that these neurons do not contain tau-immunoreactive neurofibrillary tangles. The morphological correlate of reduced somatostatin and neuropeptide Y content in Alzheimer's disease brain therefore appears to be a distortion and reduction in fiber plexuses. In addition, it is apparent that these neurons can develop widespread morphological abnormalities in the absence of neurofibrillary tangle formation. PMID- 2897824 TI - X-linked myopathy with excessive autophagy: a new hereditary muscle disease. AB - We report on 3 brothers with a myopathy that also affected their maternal grandfather and great-uncle. Characteristic features are onset in early childhood, very slow progression, normal life expectancy, weakness of proximal limb muscles, especially in the legs, elevation of serum creatine kinase, and no cardiac or intellectual involvement. In biopsy material muscle fibers are almost never necrotic but show excessive autophagic activity and exocytosis of the phagocytosed material. We suggest that this family has an undescribed type of congenital myopathy, for which we propose the name X-linked myopathy with excessive autophagy. PMID- 2897823 TI - Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. AB - Postmortem examination was performed on 137 residents (average age 85.5 years) of a skilled nursing facility whose mental status, memory, and functional status had been evaluated during life. Seventy-eight percent were demented using conservative criteria; 55% had characteristic Alzheimer's disease. Choline acetyltransferase and somatostatin were significantly reduced in the brains of patients with Alzheimer's disease as compared with age-matched nursing home control subjects, although the degree of the reduction was less severe than found in subjects less than 80 years of age. Ten subjects whose functional and cognitive performance was in the upper quintile of the nursing home residents, as good as or better than the performance of the upper quintile of residents without brain pathology (control subjects), showed the pathological features of mild Alzheimer's disease, with many neocortical plaques. Plaque counts were 80% of those of demented patients with Alzheimer's disease. Choline acetyltransferase and somatostatin levels were intermediate between controls and demented patients with Alzheimer's disease. The unexpected findings in these subjects were higher brain weights and greater number of neurons (greater than 90 micron 2 in a cross sectional area in cerebral cortex) as compared to age-matched nursing home control subjects. These people may have had incipient Alzheimer's disease but escaped loss of large neurons, or alternatively, started with larger brains and more large neurons and thus might be said to have had a greater reserve. PMID- 2897825 TI - Is the thought disorder with oculogyric crisis a feature of tardive akathisia or tardive dysphrenia? PMID- 2897826 TI - Carboxypeptidase E. AB - Carboxypeptidase E appears to be involved in the biosynthesis of a wide range of peptide hormones and neurotransmitters. The evidence for this is: (a) CPE is present in tissues that produce bioactive peptides; (b) in tissues that have been subjected to subcellular fractionation, the CPE activity is associated with peptide-containing secretory granules; (c) CPE is able to remove C-terminal basic amino acids from a variety of synthetic peptides without further hydrolyzing the peptide; (d) CPE is active at pH 5.6, the internal pH of secretory granules. The CPE activities in various tissues have similar physical and enzymatic properties. Two forms of CPE, soluble and membrane-bound, are present in most tissues with CPE activity. These two forms differ slightly in molecular weight, but have identical enzymatic properties. Both forms arise from the same precursor, which is encoded by a single gene. This gene is a member of a carboxypeptidase gene family that includes CPA and CPB. At the amino acid level, CPE has approximately 20% homology with bovine CPA and 17% homology with bovine CPB. All of the amino acids in CPA and CPB that are thought to be essential for catalytic activity are present in CPE in comparable positions. The homology of CPE with CPA and CPB suggests a common evolutionary origin for the three enzymes. This relationship fits with the theory that certain peptide hormones may have evolved from serine proteases. Further studies are needed to investigate the processing of proCPE into CPE, and the regulation of CPE activity. While there is some evidence that CPE may be regulated, it does not appear that regulation of CPE activity plays an important role in controlling peptide biosynthesis. However, further studies are necessary before this possibility can be eliminated. PMID- 2897827 TI - Peptides as regulators of gastric acid secretion. AB - Several peptides are important regulators of gastric acid secretion. The best characterized is gastrin. This circulating hormone is produced in the gastric antrum and mediates the gastric phase of acid secretion. Somatostatin is important as an inhibitory regulator of acid secretion, but the relative importance of paracrine versus endocrine delivery to its targets remains to be determined. The mammalian bombesin peptides, GRP27 and GRP10, probably are mediators of neural release of gastrin. Opioid peptides in the gastric wall appear to act as endogenous neurostimulants of gastric acid secretion under some conditions. Other neuropeptides in the gastric mucosa and submucosa, including sensory neuropeptides, may be important regulators of acid secretion. Hormones or nerves activated by fat and other substances in the lumen of the small intestine cause inhibition of acid secretion, but the specific peptides responsible for this effect have not yet been identified from a long list of candidates. The effects of peptides on the parietal cell and the gastrin and somatostatin cells are functionally linked with those of cholinergic and adrenergic nerves and with locally released histamine. PMID- 2897828 TI - Effects of putative neurotransmitters on sympathetic preganglionic neurons. AB - Epinephrine, substance P, and glutamate have all been hypothesized as primary chemical mediators in the descending pathway from the brain stem "vasomotor center" to SPNs. Interestingly, lesions of or antagonists to epinephrine, substance P, glutamate, and 5-HT neurons all abolish sympathetic activity and reduce blood pressure to a level similar to that in a spinal-transected animal. However, it is unlikely that all these substances are primary mediators of sympathetic information carried from the brain stem to the spinal cord. How then do we resolve these findings? A plausible explanation is that monoamines and neuropeptides act in the IML, as in other areas of the central nervous system, as neuromodulators, setting the level of excitability of SPNs rather than relaying sympathetic information over a functionally specific pathway from brain stem sympathetic neurons to the IML. For example, the time course of the norepinephrine-mediated slow EPSPs and IPSPs in SPNs is consistent with a gain setting function. Likewise, the depolarization of SPNs by 5-HT is similar to the depolarization elicited in myenteric and celiac ganglion cells. In these ganglia, 5-HT appears to mediate a slow excitatory potential that enhances incoming fast synaptic potentials. A similar gain-enhancing effect of 5-HT has been demonstrated in facial motoneurons. By analogy, epinephrine is likely to act as a neuromodulator in the IML rather than to serve as the primary mediator of sympathetic information descending from the brain stem. Similarly, it is difficult to imagine that an agent with such a long duration of excitatory action as substance P could serve as the primary descending transmitter in a system where moment to moment changes in activity are essential. It is more likely that substance P aids in setting the excitability of SPNs. Pharmacological antagonism of any of the excitatory neuromodulators (i.e. gain setters) might act to decrease, at least temporarily, the excitability of SPNs to the point where primary sympathetic activity from the brain stem could not excite SPNs. This accounts for the wide variety of pharmacological agents that act to eliminate sympathetic activity and drastically reduce blood pressure. On the basis of the above arguments, the most logical candidate for a transmitter mediating primary excitatory sympathetic information from brain stem "vasomotor centers" would be an excitatory amino acid. Fast EPSPs in SPNs appear to be mediated by glutamate and excitatory amino acid antagonists markedly inhibit sympathetic activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2897830 TI - Activities of Nigerian chewing stick extracts against Bacteroides gingivalis and Bacteroides melaninogenicus. AB - The in vitro activities of extracts of Nigerian chewing sticks against Bacteroides gingivalis and B. melaninogenicus are presented. The greatest inhibitory action was produced by Serindeia werneckei, whereas Fagara zanthoxyloides produced no appreciable inhibitory effect. A generally good correlation was found between the killing curves and MICs. Only extracts of Anogeissus leiocarpus showed acute toxicity in mice. PMID- 2897831 TI - Low concentrations of suramin can reduce in vitro infection of human cord blood lymphocytes with HTLV-I during long-term culture. AB - In vitro infection of human cord blood lymphocytes (CBL) with human T-cell leukemia/lymphoma virus type I (HTLV-I) was found to be reduced by suramin treatment at a concentration ranging from 10-100 micrograms/ml. At higher concentrations (500 micrograms/ml) suramin was toxic to the cells and even resulted in an increased percentage of cells positive for the p19 viral core protein. Suramin treatment at the onset of the CBL coculture with a lethally irradiated HTLV-I donor cell line (MT-2) reduced virus transmission, evaluated as number of p19+ cells, and the consequent amount of integrated provirus in the host genome. The amount of viral RNA transcripts was not reduced in CBL cocultures. On the other hand, suramin affected HTLV-I replication in infected MT 2 cells, when used at a concentration of 50 micrograms/ml, and this might contribute to the reduced infectivity of suramin-treated MT-2 cells. In addition to its antiviral effects, suramin exerted a modest positive regulation on the natural killing activity of CBL and their early proliferative response in mixed lymphocyte/tumor cell culture. PMID- 2897829 TI - Chemotherapy of rhinovirus colds. PMID- 2897833 TI - [A one-year collection of Culicidae in illuminated traps in the park around the Pasteur Institute of Madagascar in Tananarive]. AB - Culicidae captures by light traps have been done, during one year and at regular intervals in the Madagascar Pasteur Institute's park in Tananarive. 3,350 individuals representing twenty species have been caught. Results show a great specific wealth, inter and intraspecific variations in space and time and this, particularly in relation with rain. Culex quinquefasciatus is in a widely commanding position. The Madagascar Pasteur Institute's park can be considered, by number of present species, as representative of Culicidae fauna of the Tananarive's country. PMID- 2897832 TI - Effects of UVB irradiation on epidermal adenylate cyclase responses in vitro: its relation to sunburn cell formation. AB - UVB irradiation augmented the beta-adrenergic adenylate cyclase response of pig skin epidermis in vitro. The effect was observed 2-4 h following the irradiation and lasted at least for 48 h. There was no significant difference in cyclic AMP phosphodiesterase activity between control and UVB-irradiated epidermis at lower irradiation dose (150 mJ/cm2), which is the dose of the most marked beta adrenergic augmentation effect. The augmentation effect was specific to the beta adrenergic system; adenosine and histamine adenylate cyclase responses were unchanged or decreased depending on the irradiation dose. Histologically, marked sunburn-cell formation was observed following the UVB irradiation. It has been suggested that oxygen intermediates generated by ultraviolet radiation participate in sunburn-cell formation. The addition of superoxide dismutase (SOD) in the incubation medium significantly inhibited sunburn-cell formation. On the other hand, the beta-adrenergic augmentation effect was not affected by the addition of SOD. Other scavengers of oxygen intermediates (catalase, catalase + SOD, xanthine, or mannitol) did not inhibit the UVB-induced beta-adrenergic augmentation effect. Further, superoxide-anion generating systems (hypoxanthine xanthine oxidase system and acetaldehyde-xanthine oxidase system) revealed no stimulatory effect on the beta-adrenergic response of epidermis. These results indicate that (a) the UVB-induced beta-adrenergic augmentation effect is inherent to skin and does not depend on systemic factors such as inflammatory infiltrates following UVB irradiation; (b) in contrast to sunburn-cell formation, induction of the beta-adrenergic adenylate cyclase response is not directly associated with oxygen intermediates generated by UVB irradiation. PMID- 2897834 TI - The effects of antihypertensive agents on serum lipids and lipoproteins. AB - Hypertension is a major risk factor for arteriosclerotic vascular disease. Despite intensive antihypertensive intervention, the risk of cardiovascular disease has not declined appreciably. Many of the antihypertensive agents have been shown to elevate total serum cholesterol and triglyceride levels or lower the high-density lipoprotein-cholesterol level. Thus, the antihypertensive agents chosen may negate the beneficial effects of a lower blood pressure. Our purpose is to review all available antihypertensive medications and their influence on lipoprotein metabolism. Choosing the antihypertensive therapy least likely to worsen or precipitate other known cardiovascular risk factors is important. Cost and side effect profiles must also be considered in choosing the best antihypertensive regimen for your patients. PMID- 2897835 TI - Epidermolysis bullosa acquisita and Crohn's disease. A case report with immunological and electron microscopic studies. AB - A review of the literature shows that the association of epidermolysis bullosa acquisita and Crohn's disease is rare. A 27-year-old man developed cutaneous blisters on the trauma-prone areas that were consistent with the diagnosis of epidermolysis bullosa acquisita. Immunological and electron-microscopic studies of the skin showed intense IgG deposits located beneath the basal lamina. Three years later, Crohn's colitis was diagnosed. Prednisolone and sulfasalazine treatment resulted in an improvement of the bowel disease but without appreciable effect on the skin lesions. PMID- 2897837 TI - Somatostatin immunoreactivity in postmortem brain from depressed suicides. PMID- 2897836 TI - Effect of neuroleptics on altered cerebral glucose metabolism in schizophrenia. AB - This study examines whether the duration of treatment with antipsychotic drugs influences the regional distribution of cerebral [18F]2-fluoro-2-deoxy-D-glucose utilization as measured by positron emission tomography. Two groups of schizophrenic patients are compared with normal volunteers (n = 10). One group (n = 5) consisted of patients treated for one year, and the second (n = 12) of patients medicated for four to 14 years (mean +/- SD duration, 7.4 +/- 3.4 years). The first group was also examined before patients received their first dose ever of antipsychotic medication. One year of medication was not sufficient to alter the schizophrenic profile of cerebral cortical glucose activity but did elevate activity of the corpus striatum. Medication for 7.4 years also did not alter the schizophrenic pattern of frontal hyperactivity and posterior hypoactivity, although deviations from control values appeared less marked than after one year. On the other hand, in patients medicated for 7.4 years, there was perhaps an even greater increase in the activity of the corpus striatum and of the thalamus. Thus, duration of exposure to antipsychotic medication may affect the pattern of cerebral glucose activity; possibly, even longer exposure may contribute to the hypofrontality noted by others, although this can be confounded with the duration of illness as a factor. In considering the biological significance of the observed profile of cortical glucose activity, we introduce the concept of cerebral metabolic tone. We suggest that a disturbance of this tonus may account for some symptoms of schizophrenia and could be consistent with the hypothesis of abnormal developmental changes in the brains of schizophrenics. PMID- 2897838 TI - Isolated polyarteritis of testis in hairy-cell leukemia. AB - A polyarteritis nodosalike systemic vasculitis in hairy-cell leukemia was first reported in 1979, and since then at least 30 additional cases of this unusual association have been reported in the literature. Reported herein is, to my knowledge, the first known example of hairy-cell leukemia with necrotizing vasculitis limited to the testis only. PMID- 2897839 TI - [Research on human retroviruses: present status and future outlook]. PMID- 2897840 TI - [Characteristics of morphogenesis of cryptorchism in childhood]. AB - The main morphological features of undescended testes in children of 2-14 years old were incomplete cytodifferentiation of Sertoli cells (absence of transition of Sa = Sb cells into Sc type), reduced number of spermatogonia and dystrophic changes in germ cells. Intense progressive sclerosis developed in the interstitium and walls of seminiferous tubules. The dark Sertoli cells were described as a distinct cell type for the first time. The results of the morphological study indicated that cryptorchism should be surgically corrected during the first two years of life. PMID- 2897841 TI - Mode of action of lipid-lowering drugs. AB - Following the recent demonstration that both cholestyramine and nicotinic acid decrease mortality from coronary heart disease, there is a new enthusiasm for hypolipidaemic therapy. The agents in current use are, however, insufficiently active or are accompanied by unacceptable side effects. An understanding of the mode of action is necessary, both to optimize treatment guidelines (e.g. regarding combination therapy or use in specific subsets of patients) and to develop new agents with preferred actions on rate-limiting steps. A reduction in LDL cholesterol concentration remains the principal desired action, although an elevation in HDL may also be beneficial. The main categories of commercially available agent comprise the anion exchange resins (inhibitors of bile acid absorption); cholesterol absorption inhibitors; fibrates (probably acting by enhancing lipoprotein lipase); and probucol (affecting LDL clearance). The most interesting of the new agents in clinical trials are the beta-hydroxy-beta methylglutaryl-CoA reductase inhibitors, but other types of agent are at an earlier stage of evaluation, e.g. acyl-CoA: cholesterol acyltransferase inhibitors and peptide cofactors. It is not yet certain whether all the approaches to cholesterol lowering have equal validity, although an effect on biological endpoints is obtained for a variety of agents. Future evaluation will be aided by the implementation of noninvasive methods to quantify atherosclerosis and by the use of simple, 'dry-chemistry', cholesterol assays to screen populations. PMID- 2897842 TI - Autonomic responses and neurohumoral control in the human early antenatal heart. AB - Previous sporadic findings and the results of recent, more systematic studies now permit us to make an attempt to outline the contribution of the sympathetic and parasympathetic system to the control of the human early antenatal cardiac function. In the developing heart of man, only acetylcholine and catecholamines have so far been proven to act as true autonomic transmitters. Muscarinic cholinergic responses to acetylcholine and related agents can be detected from the 4th postconception week onwards, i.e. soon after the initiation of the first heartbeats. The same applies to the beta-adrenergic responsiveness to noradrenaline, adrenaline and other adrenergic stimulants in a somewhat later period, commencing at week 5 after conception. The maximum cardiac response to all these agonists becomes stronger as development continues. Evidence is accumulating to suggest that prostaglandins and triiodothyronine might modulate the regulatory function of autonomic transmitters in the human early antenatal heart. Morphological and functional establishment of the autonomic innervation occurs in the human heart well after the appearance of the reactivity to autonomic transmitters. Under 'in vitro' conditions, muscarinic-cholinergic neuro effector transmission can be demonstrated in 10-12 week-old hearts, and cardiac beta-adrenergic transmission can first be detected in weeks 13-14. From these observations and from the appearance of the 'in utero' fetal tachycardiac response to atropine in weeks 15-17 and the bradycardiac response to beta blockers in weeks 23-28, it seems that the parasympathetic-cholinergic control of the developing human heart becomes functional and can play a role in the overall regulation of the antenatal cardiac function earlier than the sympathetic adrenergic neural control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897844 TI - Ketotifen prevents terbutaline-induced down-regulation of beta-adrenoceptors in guinea pig lung. AB - We examined the effect of ketotifen on the down-regulation of beta-adrenoceptors in guinea pig lung chronically treated with terbutaline. There was a significant decrease in the density of beta-adrenoceptors following chronic administration of terbutaline. Ketotifen prevented the decrease in beta-adrenoceptor density induced by terbutaline in a dose-dependent fashion; ketotifen alone, also increased the density of beta-adrenoceptors. However, neither ketotifen nor terbutaline significantly changed the KD values in either group. These findings suggest that ketotifen might be valuable when beta-agonists are administered for long term treatment in asthmatic patients. PMID- 2897843 TI - On the glutamate transport through cell envelope vesicles of Halobacterium halobium. AB - Glutamate uptake by envelope vesicles of Halobacterium halobium was measured. Previous authors showed that the glutamate uptake needs the illumination as well as Na+ gradient across the membrane. The latter is considered to be the driving force for the uptake. No satisfactory explanation for the necessity of the illumination has not been given. We found that in the absence of Cl- in the medium, only Na+ gradient was enough to induce the glutamate uptake, i.e. no illumination was needed. Glutamate uptake was measured with various strains of H. halobium. We found that the envelope vesicles prepared from strains containing no bacteriorhodopsin showed the glutamate uptake in the dark and in the presence of Cl- in the medium provided only that Na+ gradient is imposed. PMID- 2897845 TI - Exact localization of the familial dysbetalipoproteinemia associated HpaI restriction site in the promoter region of the APOC1 gene. AB - An HpaI restriction fragment length polymorphism (RFLP) in the APOE-C1-C2 gene cluster on chromosome 19 is strongly associated with familial dysbetalipoproteinemia (type III hyperlipoproteinemia). Recently we localized this polymorphic HpaI site between the APOE and APOC1 genes. In the present paper we show by molecular cloning and sequencing that the polymorphic HpaI site is located 317 bp upstream of the transcription initiation site of the APOC1 gene. Overlapping cosmid clones allowed the construction of a detailed restriction map of the gene cluster, showing the APOC2 gene to be located 15 kb downstream of the APOC1 pseudogene. PMID- 2897846 TI - IF1 inhibition of mitochondrial F1-ATPase is correlated to entrapment of four adenine- or guanine-nucleotides including at least one triphosphate. AB - This paper demonstrates that the inhibition of F1 ATPase activity by the natural inhibitor protein IF1 is correlated to triphosphate nucleotide entrapment in F1. The complete balance of nucleotides bound after preincubation with Mg-[alpha 32P]GTP or Mg-[alpha-32P]ATP, used to promote IF1 inhibition, has been established on purified F1 containing 0.7 mol of non-exchangeable endogenous nucleotides. As many as 4 mol of labelled guanine- or adenine- nucleotides are trapped in F1; at least one of these nucleotides is a triphosphate. On the contrary, in the absence of IF1, no triphosphate nucleotide is significantly retained and the diphosphate nucleotides bound are mainly exchangeable. PMID- 2897847 TI - Clostridium spiroforme toxin is a binary toxin which ADP-ribosylates cellular actin. AB - We have purified from Clostridium spiroforme strain 246 an heterogeneous population of proteins (Sa) ranging from 43 to 47 kilodaltons exhibiting ADP ribosyl transferase activity as do C. botulinum C2 toxin component I or the ia chain of C. perfringens E iota toxin. C. spiriforme Sa had alone no activity upon injection in mice or inoculated to Vero cells. When spiroforme ADP ribosyl transferase were mixed with a trypsin activated protein (Sb) separated from C. spiroforme bacterial supernatant, a lethal effect in mice and cytotoxicity on Vero cells were recorded. The Sa cross-reacted immunologically with either the light chain of C. perfringens E iota toxin or the ADP-ribosyl transferase from C. difficile 196 strain. No immunological relatedness was observed between Sa and C2 toxin component I. C. spiroforme toxin is thus another binary toxin close to iota. PMID- 2897849 TI - Restriction fragment analysis confirms the position 33 mutation in transthyretin from an Israeli patient (SKO) with familial amyloidotic polyneuropathy. AB - Transthyretin isolated from amyloid fibrils from an Israeli patient with Familial Amyloidotic Polyneuropathy was sequenced by two research groups. One laboratory reported a position 49 Thr----Gly substitution, while the other noted a Phe for Ile interchange at amino acid 33. We used a transthyretin cDNA probe to study DNA from this patient by Southern blotting. The DNA displayed the unique Bcl I restriction site predicted by the mutation in codon 33. Because of the close size of the normal (6.40 kb), and variant (6.27 kb) fragments, the variant was more easily demonstrated after digestion with both Bcl I and Sph I, which generated two easily resolvable fragments of 2.39 and 2.27 kb. PMID- 2897848 TI - Inhibition and photoinactivation of the bovine heart mitochondrial F1-ATPase by the cytotoxic agent, dequalinium. AB - The bovine heart mitochondrial F1-ATPase is inhibited in the dark by the amphipathic cation, dequalinium, with a I0.5 of about 12 microM at pH 7.5. When illuminated at 350 nm in the presence of 1.7 microM dequalinium, the F1-ATPase is inactivated with a pseudo-first order rate constant of 7.9 X 10(-3) min-1. The apparent Kd of the dequalinium-enzyme complex was estimated to be about 12.5 microM by examining the rate of inactivation of the ATPase with 1.7-16.7 microM dequalinium. ATP, ADP, Pi, and Mg2+, singly or in combination, protected the ATPase against photoinactivation, with Mg2+ plus Pi being the most effective. PMID- 2897850 TI - The mosquito larvicidal activity of 130 kDa delta-endotoxin of Bacillus thuringiensis var. israelensis resides in the 72 kDa amino-terminal fragment. AB - Bacillus thuringiensis var. israelensis produces 130 kDa delta-endotoxin which is highly toxic to mosquito-larvae. The mosquito-larvicidal activity was delineated by sequential deletions from ends of the 1136 amino acids delta-endotoxin. A maximum of 459 amino acids could be removed from the carboxy-terminal of the toxin without a significant loss of the larvicidal activity. However, no more than 38 amino acids could be deleted from the amino-terminal without losing the toxicity. The truncated peptide of 72 kDa exhibited similar toxicity to the 130 kDa toxin and was between 39th and 677th amino acids. PMID- 2897851 TI - Site-directed mutagenic replacement of glu-461 with gln in beta-galactosidase (E. coli): evidence that glu-461 is important for activity. AB - Glutamic acid 461 of beta-galactosidase (E. coli) was replaced by gln using site directed mutagenesis. Kinetic studies on the purified Q461-beta-galactosidase showed that it had less than 0.4% of the wild-type activity (with ONPG as substrate), confirming other studies which have suggested that the negative charge on glu-461 is important for activity. The Km values did not increase, indicating that binding of the substrate was not decreased by this change. Thermal denaturation studies showed Q461-beta-galactosidase to be somewhat more susceptible to heat denaturation than the wild-type enzyme. PMID- 2897852 TI - Synergistic cytotoxic effect of tiazofurin and ribavirin in hepatoma cells. AB - Tiazofurin, an anti-cancer drug, which induces remissions in human leukemia, and ribavirin, an anti-viral agent, bind at separate sites (NADH and IMP-XMP sites, respectively) on the target enzyme, IMP dehydrogenase. Now we show that the binding to IMP dehydrogenase of these drugs at two separate sites is translated into synergistic inhibition of de novo guanylate biosynthesis and synergistic toxicity in rat hepatoma 3924A cells. These results may be utilized in the chemotherapy of neoplastic diseases and in the treatment of hepatitis virus infection and hepatocellular carcinoma. PMID- 2897853 TI - Regulation of hepatic cholesterol biosynthesis by fatty acids: effect of feeding olive oil on cytoplasmic acetoacetyl-coenzyme A thiolase, beta-hydroxy-beta methylglutaryl-CoA synthase, and acetoacetyl-coenzyme A ligase. AB - We reported previously that, in the perfused rat liver, oleic acid increased the specific activity of cytosolic enzymes of cholesterol biosynthesis. In this study, we examined the effects of oral administration of olive oil on the activities of HMG-CoA synthase, AcAc-CoA thiolase, AcAc-CoA ligase and HMG-CoA reductase. Olive oil feeding increased the specific activity of hepatic HMG-CoA synthase by 50%, AcAc-CoA thiolase by 2-fold, and AcAc-CoA ligase by 3-fold. Olive oil had no effect on HMG-CoA reductase activity. These data suggest that the enzymes that supply the HMG-CoA required for hepatic cholesterogenesis are regulated in parallel by a physiological substrate, fatty acid, independent of HMG-CoA reductase under these conditions. PMID- 2897854 TI - In vitro and in vivo inhibition of human small cell lung carcinoma (NCI-H69) growth by a somatostatin analogue. AB - An endocrinologically-potent octapeptide analogue of somatostatin (SRIF), 3-(2 naphthyl)-D-Ala-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (BIM-23014 C), was examined for its ability to inhibit the in vitro and in vivo growth of the human small cell lung carcinoma (SCLC) line, NCI-H69. When cultured cells were implanted into athymic nude mice, treatment (500 micrograms/injection, twice daily) resulted in a prolongation of lag time for the appearance of measurable tumors, and there was a marked inhibition of the growth rate. Indeed, peptide injection in the region of the tumor resulted in a complete regression of the NCI-H69 tumors. Withdrawal of BIM-23014 C treatment resulted in an acceleration of tumor growth indicating an antiproliferative rather the oncolytic action. A similar inhibition of tumor growth was also observed when solid tumors obtained from the first implantation were used as the donor tissues. In cell culture, the proliferation in the presence of a low concentration (10nM) of BIM-23104 C was also significantly retarded suggesting a direct mechanism of action. PMID- 2897855 TI - Modulation of guinea-pig lung adenylate cyclase by ovalbumin sensitization. AB - 1. The regulation of lung adenylate cyclase was investigated in guinea pigs sensitized with high dose (300-500 micrograms kg-1) ovalbumin to raise IgG(I) and low dose (2.8-4.0 micrograms kg-1) to raise to IgG/IgE (II) antibodies. 2. Basal activity of sensitized II (IgG/IgE antibodies) lung adenylate cyclase was approximately double that of the control values. 3. Guanosine 5'-triphosphate (GTP) was a potent activator of adenylate cyclase from the sensitized II (IgG/IgE) lung membranes. 4. The sensitivity of lung membrane adenylate cyclase to stimulation by beta-adrenoceptor agonists or VIP was reduced whereas no significant difference was observed with histamine or bradykinin on the sensitized II membranes. 5. Possible mechanisms involved in the increase in basal activity and in the decreased sensitivity to beta-adrenoceptor- and VIP-mediated stimulation of adenylate cyclase by ovalbumin sensitization of guinea-pig lung membranes are discussed. PMID- 2897856 TI - Vasopressin V1 receptors and inter-receptor regulation in vascular smooth muscle cells. PMID- 2897857 TI - Calmodulin antagonists of improved potency and specificity for use in the study of calmodulin biochemistry. AB - Syntheses are described for a range of N-(omega-aminoalkyl)-5-iodo- and -5 cyanonaphthalene-1-sulphonamides. The selective activity of these compounds as inhibitors for calmodulin-dependent phosphodiesterase (EC 3.1.4.17) is compared with their activity for the calmodulin-independent but calcium-dependent enzymes protein kinase C and transglutaminase (EC 2.3.2.13). The results show a drastic improvement in the selectivity of effect for the 5-iodo-compounds compared with the widely-used drug, W7, N-(6-aminohexyl)-5-chloronaphthalene-1-sulphonamide. PMID- 2897859 TI - Successful management of catastrophic gastrointestinal involvement in polyarteritis nodosa. AB - A patient with polyarteritis nodosa developed necrotizing enterocolitis, as indicated by pneumatosis intestinalis seen on computed tomographic scans of the abdomen. Despite immunosuppressive therapy and concomitant resolution of the intramural and portal venous gas and general clinical improvement, on 2 occasions (between 20 and 30 days later) the patient developed bowel infarctions and perforations that necessitated bowel resection. Leaks developed at anastomotic sites, but were not closed surgically. However, these sites and the lower quadrants of the abdomen were drained, and the patient was given total parenteral nutrition. Over a 2-month period the patient completely recovered from this nearly always fatal gastrointestinal complication of polyarteritis nodosa. The medical, surgical, and radiographic approach we used may be applicable to the management of similar cases in the future. PMID- 2897858 TI - Mechanisms of synergistic toxicity of the radioprotective agent, WR2721, and 6 hydroxydopamine. AB - WR2721 is a "prodrug" for a radioprotective thiol which has been proposed for adjunctive use as a free radical scavenger in cancer chemotherapy. When used adjunctively with oxygen radical generating chemotherapeutic agents in mice, however, WR2721 produces synergistic toxicity rather than attenuation of the toxic effects of such agents. The present paper discusses potential mechanisms for such synergistic toxicity. The pathway for glutathione synthesis appeared to be inactivated in mice treated with WR2721. The disulfide metabolite of WR2721 was a potent inactivator of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in glutathione synthesis. The inactivation of the enzyme by this compound was similar to that reported for cystamine, a compound known to form a mixed disulfide with a cysteine residue near the glutamic acid binding site of the enzyme. Oxygen radicals not only inactivated the synthetase, as well, but hastened the oxidation of the free thiol metabolite of WR2721 to its corresponding disulfide. PMID- 2897860 TI - The fractional catabolic rate of low density lipoprotein in normal individuals is influenced by variation in the apolipoprotein B gene: a preliminary study. AB - In a random sample of 22 normolipidaemic male Caucasian individuals, 35-49 years old, homozygosity for the X2 allele (cutting site) of the XbaI RFLP of the apo B gene was associated with higher mean total cholesterol and LDL-cholesterol concentration. These individuals also had significantly lower LDL fractional catabolic rate (P less than 0.03) and a lower degradation of LDL by mononuclear cells in vitro. We propose that the XbaI polymorphism is associated with amino acid changes in the apo B protein which influences LDL binding to the LDL receptor. This modulates catabolism of this lipoprotein and so contributes to variability of plasma cholesterol levels. PMID- 2897861 TI - Fade profiles during spontaneous offset of neuromuscular blockade: vecuronium and gallamine compared. AB - The characteristics of the train-of-four (TOF) response have been studied electromyographically during the onset and the spontaneous offset of neuromuscular blockade induced with vecuronium or gallamine. During the onset of blockade, at 75% depression of initial twitch height, gallamine was associated with significantly more TOF fade than vecuronium. Both agents were associated with significantly less fade during onset than during spontaneous offset. When the two neuromuscular blocking drugs were compared during spontaneous offset they showed a similar degree of fade during early offset (up to 50% recovery of initial twitch height). However, during late spontaneous offset, when the initial twitch height had recovered to 75% of control values, vecuronium was associated with more fade than gallamine. PMID- 2897862 TI - Pulmonary clearance of UICC amosite fibres inhaled by rats during chronic exposure at low concentration. AB - Clearance of UICC amosite asbestos from the lungs during chronic--that is, repeated--exposure was investigated by using the scanning electron microscope to measure lung burdens from rats which had inhaled amosite asbestos at an approximately constant concentration of 0.1 mg/m3 or, equivalently, 20 fibres/ml for seven hours a day, five days a week for up to 18 months. The lung burdens were compared with previous results for higher exposure concentrations of 1 and 10 mg/m3. Those previous lung burdens had been measured using other analytical methods (infrared spectrophotometry) that were not suitable for the new lower lung burdens. Taken together, these results showed lung burdens rising pro rata with exposure concentration and exposure time. This accumulation of lung burden has been described by a kinetic model that takes account of the sequestration of material at locations in the lung from where it cannot be cleared. Unlike some earlier models in which lung burdens eventually reach a plateau with equilibrium between deposition and clearance during chronic exposure, this sequestration model shows lung burdens continuing to rise with exposure time. The latest results reported here support the application of such a model to lower exposure concentrations closer to those of asbestos in workplaces. PMID- 2897863 TI - Expression of a human alpha-tubulin: properties of the isolated subunit. AB - We examined the in vitro expression and biochemical properties of the isolated alpha subunit of tubulin both in rabbit reticulocyte lysates and in Escherichia coli extracts. Both systems produce soluble, full-length human alpha-tubulin polypeptide. When alpha-tubulin mRNA is translated in rabbit reticulocyte lysates, the isolated alpha subunit is fully functional as assayed by coassembly with bovine brain tubulin using temperature-dependent or taxol/salt assembly procedures. The conformation of the isolated alpha subunit was probed by limited proteolytic digestion with chymotrypsin and by reductive methylation. Limited proteolysis studies indicated that the "monomeric" alpha subunit is highly susceptible to chymotrypsin digestion and becomes resistant to chymotrypsin cleavage following incorporation into the heterodimer. Reductive methylation indicated that the unassociated alpha subunit has a highly reactive lysyl residue essential for microtubule assembly similar to that observed in the heterodimer. In contrast, alpha-tubulin expressed in E. coli lysates was incapable of coassemblying with bovine brain tubulin. Differences in assembly competence of the two alpha-tubulin products appear to be related to formylation of the N terminal methionine in the procaryotic synthesized subunit. These findings suggest that the amino-terminal methionine of alpha-tubulin plays an essential role in the isolated subunit and/or in the heterodimer, a hypothesis supported by chemical reactivity studies [Sherman, G., Rosenberry, T.L., & Sternlicht, H. (1983) J. Biol. Chem. 258, 2148-2156] which imply that this residue is in a salt bridge interaction in the dimer. PMID- 2897864 TI - Action of the active metabolites of tiazofurin and ribavirin on purified IMP dehydrogenase. AB - The inhibitory mechanisms of ribavirin 5'-monophosphate (RMP) and thiazole-4 carboxamide adenine dinucleotide (TAD), the active forms of the antimetabolites ribavirin and tiazofurin, were investigated in IMP dehydrogenase purified to homogeneity from rat hepatoma 3924A. The hepatoma IMP dehydrogenase has a tetrameric structure with a subunit molecular weight of 60,000. For the substrates IMP and NAD+, Km's were 23 and 65 microM, respectively. Product inhibition patterns showed an ordered Bi-Bi mechanism for the enzyme reaction where IMP binds to the enzyme first, followed by NAD+; NADH dissociates from the ternary complex first and then XMP is released. XMP interacts with the free enzyme and competes for the ligand site with IMP, while NADH binds to the enzyme XMP complex. RMP exerted the same inhibitory mechanisms as XMP, and the inhibition by TAD was similar to that by NADH. However, the Ki values for RMP (0.8 microM) and TAD (0.13 microM) were orders of magnitude lower than those of XMP (136 microM) and NADH (210 microM). Thus, the drugs interact with IMP dehydrogenase with higher affinities than the natural substrates and products, RMP with the IMP-XMP site and TAD with the NADH site. Preincubation of the purified enzyme with RMP enhanced its inhibitory effect in a time-dependent manner. The enzyme was protected from this inactivation by IMP or XMP. These results provide a biochemical basis for combination chemotherapy with tiazofurin and ribavirin targeted against the two different ligand sites of IMP dehydrogenase. PMID- 2897865 TI - Effects of footshock stress on the sensitivity of the isolated rat pacemaker to catecholamines. AB - The effect of repeated footshock on the sensitivity of the isolated rat pacemaker to the chronotropic effect of catecholamines was studied. Footshock stress caused subsensitivity to noradrenaline and supersensitivity to isoprenaline. The subsensitivity to the neurotransmitter was abolished by cocaine, whereas supersensitivity to isoprenaline was unchanged after blockade of the extraneuronal uptake. The pA2 value of metoprolol was increased by repeated footshock. Butoxamine reversed the supersensitivity to isoprenaline and the alteration of the pA2 value. Repeated footshock stress appears to cause prejunctional subsensitivity to noradrenaline and to increase the function of postjunctional beta 2-adrenoceptors. PMID- 2897866 TI - Health of long term benzodiazepine users. PMID- 2897867 TI - Effects of noradrenaline on the responsiveness of cultured cerebellar neurons to excitatory amino acids. AB - The effects of noradrenaline (NA) on the responsiveness of cultured cerebellar neurons to excitatory amino acids were intracellularly investigated. NA applied to external medium to a final concentration of 10 microM or lower slightly decreased the firing frequency of spontaneous spikes, induced a small hyperpolarization or slightly increased the input resistance of Purkinje cells. In addition, bath-applied NA was found to enhance the depolarizations induced by iontophoretically applied glutamate and aspartate but to a smaller extent for the latter. These direct and modulating effects of NA were also observed when NA was applied by iontophoresis. The sites sensitive to iontophoresed NA were found to be not uniformly distributed but localized in restricted regions on individual Purkinje cells. The enhancement by NA of the glutamate or aspartate response was blocked by beta-adrenergic antagonists, propranolol or pindolol, and extracellularly applied cAMP mimicked the NA action. These results suggest the possibility that NA physiologically modulates excitatory amino acid-mediating synaptic transmission in the cerebellum probably by acting on beta-rather than alpha-adrenergic receptors. PMID- 2897868 TI - NMDA receptor activation and early olfactory learning. AB - Norway rat pups have an enhanced olfactory bulb response to odors which they have learned to prefer early in life. When N-methyl-D-aspartate receptors are blocked pharmacologically before olfactory preference training, both the behavioral preference and the enhanced olfactory bulb response to the learned odor are suppressed. These results implicate the activation of these receptors in the kind of neural and behavioral plasticity that normally occurs during development. PMID- 2897869 TI - Methylmercury-induced movement and postural disorders in developing rat: loss of somatostatin-immunoreactive interneurons in the striatum. AB - Tissue concentrations of the neuropeptide somatostatin and the specific activities of glutamic acid decarboxylase (GAD) were measured in several regions of the central nervous system in young rats, following chronic postnatal administration of methylmercuric chloride. By the beginning of the fourth postnatal week, these animals exhibited clinical signs of a mixed spastic/dyskinetic syndrome with visual deficits. At the onset of neurological impairment, a significant decrease in GAD activity was detected in the occipital cortex (48-49%) and striatum (45-50%) when compared to either normal or weight matched controls. At one subclinical stage of toxicity, decreased GAD activity was detected only in the occipital cortex (29-30%). Tissue levels of somatostatin did not change significantly in the occipital cortex of methylmercury-treated animals at any stage of the experiment. However, somatostatin levels in the striatum were significantly reduced at the onset of neurological impairment (55 57%) and at one subclinical stage of toxicity (49-54%). Immunohistochemistry for somatostatin- and neuropeptide Y-immunoreactive neurons confirmed a marked loss of cells in the dorsolateral region of the striatum with atrophy of the surviving neurons. In the cerebral cortex of methylmercury-treated animals the morphology and distribution of somatostatin-positive neurons appeared normal. In view of the reported co-localization of GAD and somatostatin in some non-pyramidal neurons of the cerebral cortex, these results indicate that methylmercury-induced lesions of the developing cerebral cortex involve a subpopulation of GABAergic neurons which are not co-localized with somatostatin. In the striatum, where GAD and somatostatin are not co-localized within the same neurons, methylmercury-induced lesions involve both GABAergic and somatostatin-positive neurons. PMID- 2897870 TI - Development of somatostatin-containing neurons and fibers in the rat hippocampus. AB - Using a combination of in situ hybridization and immunohistochemistry, the development of somatostatin (SS)-containing neurons and fibers was examined in the rat dorsal hippocampus and dentate gyrus. The major development of this hippocampal peptidergic system occurs postnatally. At postnatal day 1 (P1), neurons containing SS mRNA are evident primarily in the stratum oriens, but also in the hilus of the dentate gyrus. Similar neurons are also immunoreactive for SS28 and SS28(1-12), suggesting a minimal lag in the transcription of SS mRNA and its translation into specific SS peptides. The number of SS neurons increases postnatally to P10, followed by a decrease in number in the adult. This transient change in the number of SS neurons coincides with dramatic changes in SS28(1-12) immunoreactive fibers, which are initially present in the stratum lacunosum moleculare, with no significant immunoreactivity in the dentate gyrus. By P15, the molecular layer of the dentate gyrus is densely innervated, while similar immunoreactivity in the stratum lacunosum moleculare is greatly reduced. These data are consistent with a transient projection from the stratum oriens to the stratum lacunosum moleculare, which is replaced by a projection from the hilus to the molecular layer of the dentate gyrus as this structure matures. PMID- 2897871 TI - Distorted development of intracerebral grafts: long-term maintenance of tyrosine hydroxylase-containing neurons in grafts of cortical tissue. AB - Cortical cells obtained from rat embryos (ED14 to ED20) were implanted in various regions of rat brain and the presence of tyrosine hydroxylase (TH)-, neuropeptide Y (NPY)- and Met-enkephalin (ENK)-immunoreactive neurons within the grafts were tested using an immunohistochemical approach. TH-like immunoreactive (TH-LI) neurons were present within the implants obtained from ED14, but not ED18 or ED20, embryos up to 10 months post-implantation and their presence was not dependent on the age of the host (adult or neonate) at the time of implantation. Furthermore, the density of such cells varied with the site of implantation, being the highest in the dorsomedial corner of the striatum. This distorted development seems to affect also other cell populations, such as NPY-LI neurons which could be observed within the implants in a density much higher than that found in the normal cortex and which presented generally a rather immature morphology. It has been described that the rat cortex contains TH-LI neurons only during a limited period of development. The survival of such neurons within intracerebral grafts of cortical tissue indicates that their disappearance during normal cortical development is dependent upon environmental cues. The survival of TH-LI cells in grafts implanted to neonatal hosts suggests that these cues are not some humoral factors appearing postnatally. On the other hand, the present observations are compatible with several other hypothesis concerning the nature of such cues: humoral factors present during the late embryonic period, signals dependent on neuronal connectivities (input and/or outputs) established during embryonic or postnatal life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897872 TI - The presence of non-neuronal cells influences somatostatin release from cultured cerebral cortical cells. AB - We examined the effect of non-neuronal cells on somatostatin release from cultured cerebral cortical cells. Three culture models were used: (1) neuron enriched cultures obtained from cortex of 17-day-old rat embryos and exposed to 10 microM cytosine arabinoside (Ara C) for 48 h between days 3 and 5 after plating; (2) whole cell cultures obtained by using the same protocol but untreated with Ara C; (3) glial primary cultures obtained from newborn rats. We studied: (i) the cellular composition of the cultures by using two astroglial markers: vimentin and glial fibrillary acidic protein (GFAP); (ii) the spontaneous and forskolin-stimulated somatostatin release. In 8-day-old cultures morphological data revealed that Ara C treatment reduced glial cells to 6%. At 7 and 10 days of culture somatostatin spontaneously released from Ara C-treated cells was higher than that measured from untreated cells. On the 17th day of culture, neuron-enriched cultures contained a lower amount of somatostatin than whole cell cultures. Forskolin elicited a dose-dependent release of somatostatin from whole cell cultures, but had no effect on neuron-enriched cultures. Astroglial released media (ARM) from glial primary cultures exposed to forskolin for 20 min induced somatostatin release from neuron-enriched cultures. HPLC analysis of endogenous amino acids of ARM showed that glutamate, glutamine, glycine and alanine were significantly increased after forskolin stimulation. Our results suggest a functional interaction between glial cells and neurons secreting somatostatin. PMID- 2897873 TI - [Selective reduction by serotonin, of neuronal excitation in the locus coeruleus evoked by glutamate]. AB - In the rat, iontophoretically applied serotonin substantially attenuated the excitation of locus coeruleus neurons evoked by iontophoretic glutamate but not that elicited by acetylcholine. These results occurred independently of serotonin's variable effects on spontaneous discharge, and indicate a neuromodulatory role of serotonin in locus coeruleus. PMID- 2897875 TI - Multifactorial resistance to adriamycin: relationship of DNA repair, glutathione transferase activity, drug efflux, and P-glycoprotein in cloned cell lines of adriamycin-sensitive and -resistant P388 leukemia. AB - Cloned lines of Adriamycin (ADR)-sensitive and -resistant P388 leukemia have been established, including P388/ADR/3 and P388/ADR/7 that are 5- and 10-fold more resistant than the cloned sensitive cell line P388/4 (Cancer Res., 46: 2978, 1986). A time course of ADR-induced DNA double-strand breaks revealed that in sensitive P388/4 cells, evidence of DNA repair was noted 4 h after removal of drug, whereas in resistant clone 3 and 7 cells repair was observed 1 h after drug removal. The earlier onset of DNA repair was statistically significant (p = 0.0154 for clone 3 cells, and p = 0.0009 for clone 7 cells). By contrast, once the repair process was initiated, the rate of repair was similar for all three cell lines. The level of glutathione transferase activity was determined in whole cell extracts. Enzyme activity (mean +/- SE) in sensitive cells was 9.49 +/- 1.00 nmol/min/mg protein, that in resistant clone 3 cells was 13.36 +/- 1.03 nmol/min/mg, and that in clone 7 cells was 13.96 +/- 1.44 nmol/min/mg; the 1.44 fold increase in enzyme activity in resistant cells was statistically significant (p = 0.01). Further evidence of induction of glutathione transferase was provided by Northern blot analysis using a 32P-labeled cDNA for an anionic glutathione transferase, which demonstrated approximately a twofold increase in mRNA in resistant clone 7 cells. Western blot analysis with a polyvalent antibody against anionic glutathione transferase also revealed a proportionate increase in gene product in resistant cells. Dose-survival studies showed that ADR-resistant cells were cross-resistant to actinomycin D, daunorubicin, mitoxantrone, colchicine, and etoposide, but not to the alkylating agent melphalan; this finding provided evidence that these cells are multidrug resistant. Using a cDNA probe for P glycoprotein, a phenotypic marker for multidrug resistance, Northern blot analysis showed an increase in the steady state level of mRNA of approximately twofold in resistant clone 3 and 7 cells. Southern analysis with the same cDNA probe showed no evidence of gene amplification or rearrangement. Western blot analysis with monoclonal C219 antibody demonstrated a distinct increase in P glycoprotein in resistant cells. Efflux of Adriamycin as measured by the efflux rate constant was identical in all three cell lines. Furthermore, the metabolic inhibitors azide and dinitrophenol did not augment drug uptake in either sensitive or resistant cells. These findings suggest that despite the increase in P-glycoprotein, an active extrusion pump was not operational in these cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2897874 TI - A modified m-CP medium for enumerating Clostridium perfringens from water samples. AB - Medium m-CP, designed for the isolation of Clostridium perfringens from water samples, contains indoxyl beta-D-glucoside, an expensive chemical that is present at a high concentration in this medium. The use of m-CP with three concentrations of indoxyl beta-D-glucoside was tested at 0, 60, and 600 mg/L. Lowering the amount of indoxyl beta-D-glucoside to 60 mg/L (1/10 the recommended concentration) reduced the cost of this medium without affecting its sensitivity. PMID- 2897876 TI - The sigma receptor: a novel site implicated in psychosis and antipsychotic drug efficacy. PMID- 2897877 TI - In vivo induction of immunological memory to human tumor extract with poly (A) containing immune RNA. PMID- 2897880 TI - The modulation of excitatory amino acid responses by serotonin in the cat neocortex in vitro. AB - 1. The electrophysiological actions of excitatory amino acids and serotonin were investigated in slices from cat neocortex in vitro. Intracellular recordings were obtained from neurons (mainly in layer V) and the drugs applied extracellularly to the same neurons by microiontophoresis. 2. Serotonin, and to some extent noradrenaline, facilitated the excitatory actions of N-methyl-D-aspartate (NMDA), glutamate, and quisqualate but caused no changes in the passive neuronal membrane properties when presented alone. Serotonin had no effect on evoked excitatory postsynaptic potentials (EPSPs) or spike afterhyperpolarizations. 3. The facilitatory effect of serotonin on the responses to NMDA was observed with both somatic and dendritic applications. It persisted during Mg2+ depletion and in the presence of tetrodotoxin and tetraethylammonium. The effect was attenuated by the serotonin antagonist cinanserin but not by methysergide. A possible underlying receptor modulation is discussed. PMID- 2897881 TI - [The effects of extracellular ATP]. PMID- 2897879 TI - Neuroendocrine gene expression in the hypothalamus: in situ hybridization histochemical studies. AB - 1. We have reviewed recent studies in which in situ hybridization histochemistry (ISHH) was used to investigate the regulation of expression of neurohypophysial peptides and hypothalamic releasing hormones. 2. ISHH is a technique in which the presence and quantity of a specific mRNA can be determined in tissue sections with a high degree of resolution and sensitivity. 3. ISHH has been used to measure changes in cellular levels of mRNAs encoding vasopressin, oxytocin, corticotropin-releasing factor, gonadotropin-releasing hormone, thyrotropin releasing hormone and somatostatin in response to various physiological challenges. 4. A theme emerging from these studies is that changes in levels of mRNA encoding neuroendocrine peptides reflect changes in biosynthesis and secretion. PMID- 2897882 TI - Normal pharmacological and morphometric parameters in the noradrenergic hyperinnervated mutant mouse, "tottering". AB - Pharmacological and anatomical analyses of central monoaminergic and cholinergic neurons were performed in the "tottering" mouse, an autosomal recessive neurologic gene mutation that results in an overproduction of axons of the locus coeruleus and an increase in norepinephrine content in specific terminal fields. Except for the previously reported increase in norepinephrine content, all pharmacological parameters measured, including tyrosine hydroxylase activity, norepinephrine turnover, serotonin content, and choline acetyltransferase activity, in targets hyperinnervated by the locus coeruleus were normal. Immunocytochemical staining for tyrosine hydroxylase demonstrated the pronounced hyperinnervation in the "tottering" brain, whereas both serotonin and choline acetyltransferase immunostaining were similar between "tottering" and wild type. The volume of 3 target areas that are hyperinnervated by the locus coeruleus in the "tottering" mouse, the hippocampus, cerebellum, and cochlear nuclei, were normal. In addition, neuronal number and somal size in the locus coeruleus were found to be unchanged in the mutant genotype. These data demonstrate several features of the effects of the "tottering" gene: 1) compensatory changes in several adrenergic pharmacological parameters do not occur in response to the hyperinnervation of targets by locus coeruleus axons; 2) neither direct effects of the "tottering" gene on, nor compensatory changes in, the extent of cholinergic or serotonergic innervation of several targets of the locus coeruleus appear to occur; and 3) the lack of changes in size of the targets of the locus coeruleus suggest that the hyperinnervation in the "tottering" mouse is due to a direct genetic alteration of axonal growth by the locus coeruleus neurons, rather than to selective shrinkage of targets in the presence of normal terminal arbors. PMID- 2897883 TI - Two populations of somatostatin-immunoreactive neurons in the guinea pig striatum. AB - Two populations of neurons displaying somatostatin-like immunoreactivity were detected immunohistochemically in the guinea pig striatum using a monoclonal antibody. Sparse, well-stained neurons similar to those described in other species were observed throughout the guinea pig caudate-putamen. These neurons contained both neuropeptide Y and NADPH-diaphorase in addition to somatostatin. A second large population of somatostatin immunoreactive neurons in which these other substances did not coexist was found within the putamen. PMID- 2897878 TI - Cellular and molecular mechanisms controlling melatonin release by mammalian pineal glands. AB - 1. The pineal gland is regulated primarily by photoperiodic information attaining the organ through a multisynaptic pathway initiated in the retina and the retinohypothalamic tract. 2. Norepinephrine (NE) released from superior cervical ganglion (SCG) neurons that provide sympathetic innervation to the pineal acts through alpha1- and beta 1- adrenoceptors to stimulate melatonin synthesis and release. 3. The increase in cyclic AMP mediated by beta 1-adrenergic activation is potentiated by the increase in Ca2+ flux, inositol phospholipid turnover, and prostaglandin and leukotriene synthesis produced by alpha 1-adrenergic activation. 4. Central pinealopetal connections may also participate in pineal control mechanisms; transmitters and modulators in these pathways include several neuropeptides, amino acids such as gamma-aminobutyric acid (GABA) and glutamate, and biogenic amines such as serotonin, acetylcholine, and dopamine. 5. Secondary regulatory signals for pineal secretory activity are several hormones that act on receptors sites on pineal cells or at any stage of the neuronal pinealopetal pathway. PMID- 2897884 TI - Novel phenoxyalkylamine derivatives. I. Synthesis and pharmacological activities of alpha-isopropyl-alpha-[(phenoxyalkylamino)alkyl]benzeneaceton itrile derivatives. PMID- 2897885 TI - Immunofluorescent localization of transglutaminase in rat small intestine. AB - The distribution of intestinal transglutaminase was investigated by immunofluorescence microscopy using rabbit anti-guinea pig transglutaminase immunoglobulin. Transglutaminase-related antigen was demonstrated principally in the cytoplasm of villous core interstitial cells with some activity in the brush border region of the villous epithelial cells. Implications for the pathogenesis of coeliac disease are discussed. PMID- 2897886 TI - Agarose isoelectric focusing of arylsulfatase A producing a permanent record on slab gels. PMID- 2897888 TI - [Type 3 multiple endocrine neoplasia]. PMID- 2897887 TI - [Teeth in and around fracture lines treated with bonded silca wire splints]. PMID- 2897889 TI - Electrophysiologic and hemodynamic effects of chronic oral therapy with the alpha 2-agonists clonidine and tiamenidine in hypertensive volunteers. AB - Clonidine can produce symptomatic sinus bradycardia or atrioventricular (AV) block in some patients. Electrophysiologic studies have been performed after intravenous clonidine in patients showing such side effects; these have demonstrated variable depression of sinus and AV nodal function. We have evaluated the electrophysiologic and hemodynamic effects of chronic oral treatment with either clonidine (0.2 to 0.5 mg every 12 hours; n = 7) or another centrally active alpha 2-agonist, tiamenidine (0.5 to 1.5 mg every 12 hours; n = 7), in otherwise healthy hypertensive human volunteers. At dosages that modestly lowered diastolic blood pressure, both agents significantly slowed sinus rate and increased the atrial pacing rate producing AV nodal Wenckebach. Clonidine also significantly increased corrected sinus node recovery time and lowered cardiac output while similar (but statistically insignificant) trends were seen with tiamenidine. We conclude that chronic oral treatment with these alpha 2-agonists depresses sinus and AV nodal function in virtually all subjects, including those without manifest conduction system disease. PMID- 2897890 TI - Nizatidine disposition in subjects with normal and impaired renal function. AB - To test the hypothesis that renal insufficiency alters nizatidine disposition, we determined the pharmacokinetics of nizatidine and its major metabolite after a single oral dose in normal volunteers and patients with various degrees of renal dysfunction, after a single intravenous dose in normal volunteers and patients with severe renal failure and during hemodialysis. After intravenous administration the elimination half-life increased from 1.5 +/- 0.2 hours in normal volunteers to 6.9 +/- 3.3 hours in patients with renal failure. The plasma clearance decreased from 0.59 +/- 0.07 L/kg/hr in normal volunteers to 0.14 +/- 0.02 L/kg/hr in patients with renal failure. Nizatidine bioavailability was nearly 100% in normal volunteers but decreased to 75% in patients with renal failure. The volume of distribution was 1.3 +/- 0.1 L/kg in normal volunteers and was not different in patients with renal failure. Nizatidine protein binding was about 30% in normal and uremic plasma. The drug was not substantially removed by hemodialysis. Patients with creatinine clearances less than 50 ml/min/1.73 m2 should receive 150 mg nizatidine once each evening. Patients with creatinine clearances less than 20 ml/min/1.73 m2 should receive 150 mg nizatidine every other night. PMID- 2897891 TI - Schwann cells and collagen synthesis in taxol-treated nerve crush. An electron microscopic study. AB - The effect of nerve crush on collagen synthesis in rat sciatic nerve was studied by electron microscope. The crushed nerves were treated with taxol which is known to increase the amount of cytoplasmic microtubules at the expense of other cell organelles such as rough endoplasmic reticulum and Golgi complexes. The results were compared to those seen in crushed nerves without taxol treatment. After the injury the amount of collagen fibrils increased at the site of the trauma in both groups when compared to intact controls. Thin (30 mn in diameter) collagen fibrils were often arranged closely to the Schwann cell surface and were connected to deep invaginations in areas where the basal lamina had lost its typical integrity. This was concluded to indicate a probable site of collagen secretion and it provides further evidence that an adult injured nerve Schwann cell is capable of synthesizing fibrous collagen. In taxol-treated nerves additional, abnormally close connection between thin microfibrils of about 10 nm and thin 20-30 nm collagen fibrils appeared in an end-to-end fashion. The microfibrils showed occasional collagenous transverse band like structures. The rough endoplasmic reticulum and Golgi complex play an important role in the posttranslational modifications of the procollagen molecule. Taxol-induced degeneration of cell organelles such as the Golgi complex, which is also essential in the secretion of proteins may thus lead to defective maturation of collagen and may explain partly the altered collagen fibril formation. PMID- 2897892 TI - Lysyl oxidase in osteogenesis imperfecta and Marfan's syndrome. PMID- 2897893 TI - Lithium discontinuation: withdrawal or relapse? AB - The authors review the studies on discontinuation of lithium therapy in terms of subsequent relapse or possible withdrawal symptoms. Withdrawal symptoms following lithium discontinuation including heightened anxiety, sleep disturbances and irritability remain controversial. Relapse of the primary illness following lithium discontinuation is a well documented serious complication. PMID- 2897894 TI - [How to decrease the risk of myocardial infarct in patients with hypertension?]. AB - About half a million of the adult Swiss population has elevated blood pressure (greater than or equal to 160/95 mmHg); about one third of these cases has not yet been identified. In treated hypertensives, the expediency of primary prevention of myocardial infarction (MI) has until recently been questioned. However, the results of newest prospective studies show the favourable influence of blood pressure control not only in terms of reducing the incidence of stroke, but also of MI and sudden death, regardless of the drug applied. In male non smoking hypertensives, administration of beta-blockers contributes to a further reduction of the incidence of MI. With a view to reducing cardiovascular morbidity and mortality, the author recommends--besides improved detection and treatment of hypertension--also a more intensive fight against other risk factors of MI, especially against cigarette smoking and hypercholesterolaemia. PMID- 2897895 TI - Homeo box genes in murine development. AB - Considerable information has accumulated on mouse homeo box gene organization and expression. Homeo box genes are expressed in a wide variety of tissues, developmental stages, and cell lines. How can this be interpreted in view of the relationship of these genes to Drosophila morphogenetic loci? One view is that homeo box genes control determinative decisions by modulating transcription of as yet unidentified target genes. Proponents of this view are faced with two tasks: to identify developmental processes that are controlled by homeo box genes, and to identify the target genes that mediate this control. Such target genes might be identified on the basis of in vitro homeo domain-DNA interactions. Candidate morphogenetic processes might be identified on the basis of the observed patterns of homeo box gene expression. It must be stressed that finding expression in a given tissue in no way demonstrates that the expression is necessary for the determination of that tissue. The role of Drosophila homeo box genes in determinative decisions is based upon analysis of mutants to demonstrate that the pattern of homeo box gene expression determines the morphogenetic outcome. To test whether the expression of a mouse homeo box gene is involved in a determinative decision, one must disrupt the normal pattern of expression of that gene and observe the resulting morphogenetic effect. In mouse this can be approached by looking for allelism with known morphogenetic loci, by isolating mutants in homeo box genes through large-scale mutagenesis screens, or by introducing altered homeo box genes into transgenic mice. One of the most intriguing possibilities is that homeo box genes are involved in regional specification along the anteroposterior axis. In situ hybridization and Northern blot analysis have demonstrated that at least four different homeo box genes display distinct regional patterns of expression along the anteroposterior axis of the developing CNS. The expression of each of these genes has a unique anterior boundary from which expression extends posteriorly within the CNS. Hox 1.5 expression has an anterior boundary within the hindbrain just posterior to the pontine flexure. The anterior boundary of Hox 2.1 expression lies more posteriorly within the medulla of the hindbrain. Weak expression of Hox 2.5 is detected in the spinal cord just posterior to the first cervical vertebra, and maximal expression is found posterior to the second cervical vertebra.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2897896 TI - An RFLP for glycoprotein A (MN) is in linkage disequilibrium with MN and Ss. AB - Using a cDNA for glycophorin A (MN), we screened 10 unrelated Caucasians using 22 restriction enzymes for RFLPs. A common StuI RFLP was identified and shown to be in marked linkage disequilibrium with both the MN and Ss blood-group antigens in a larger group of unrelated Caucasians. This provides a DNA marker for a locus that has been of major importance in genetic and population studies. The demonstrated disequilibrium will prove useful in localizing the gene for glycophorin B and in studies of genetic and physical distances on human chromosomes. PMID- 2897897 TI - Somatic cell mapping and restriction fragment analysis of bovine genes for fibronectin and gamma crystallin. AB - DNAs from cow-hamster and cow-mouse somatic hybrid cells segregating bovine chromosomes have been analyzed by Southern blotting and hybridization with human fibronectin and gamma crystallin probes. Concordancy of retention of these bovine genes was compared to cattle isozyme loci representing previously described syntenic groups. Bovine fibronectin (FNI) and gamma crystallin (CRYG) fragments were concordant with each other and with isocitrate dehydrogenase 1 (IDH1), representing the bovine syntenic group U17. The syntenic relationship of these genes is conserved on human chromosome 2q and also on mouse chromosome 1. In addition, bovine RFLPs were identified with both fibronectin and gamma crystallin probes. These polymorphisms will be used to study recombination between the syntenic loci in pedigreed herds and to mark a segment of the bovine genome that is likely homologous to the Lsh region of mouse chromosome 1, which confers resistance in mice to several intracellular parasites. PMID- 2897898 TI - Gastric, duodenal, and pancreatic somatostatin-like immunoreactivity during hypovolemic shock. AB - Because hypovolemic shock is known to cause gastric ulcers in animals and human beings, we investigated the tissue levels of somatostatin-like immunoreactivity (SLI) in the gastric corpus and antrum, duodenum, and pancreas during hypovolemic shock in rats. We studied male Wistar rats (N = 10 each) 15 min, 2 hr, and 12 hr after hypovolemic shock and compared results to a control group (N = 15). Two rats in both 2-hr and 12-hr groups showed gastric ulcers: three corporal and one antral. One animal developed multiple ulcers. In the gastric corpus and antrum and in the duodenum, tissue SLI showed significant decrease 15 min and 2 hr after shock. Gastric SLI remained low, whereas duodenal SLI recovered and rose above control level at 12 hr. Pancreatic SLI showed no significant changes during hypovolemic shock. Gastric tissue SLI levels that were significantly lower after shock than those of normal controls may have contributed to the peptic ulcer disease induced by hypovolemic shock in this experimental model. PMID- 2897899 TI - [Self-restoring synaptic transmission in the hippocampus]. PMID- 2897900 TI - [Hantaan virus infections as a cause of acute kidney failure. 3 cases in West Germany]. AB - Three cases of Hantaan virus infection (Korean haemorrhagic fever) leading to acute renal failure are described. All three had mild haemorrhagic fever with a renal syndrome. It had started with acute fever followed by oliguria, proteinuria and microhaematuria (in two patients) in the further course of the disease, as well as urea and creatinine retention. One patient needed to be dialysed twice. Hantaan virus-specific IgG antibodies were demonstrated in all three patients; one also had IgM antibodies. PMID- 2897901 TI - [Parkinson disease. The clinical picture and therapy]. PMID- 2897902 TI - The potential for added benefits with beta-blockers and calcium antagonists in treating cardiovascular disorders. AB - Whereas the beta-blockers were heralded as the drugs of the sixties and early seventies, the calcium antagonists have established themselves as the drugs of the eighties. However, despite the widely differing pharmacology of these 2 classes of drugs, they are often used for the management of the same cardiovascular disorders, including angina pectoris, ischaemic heart disease and hypertension. Whether some advantage might be gained from their combined use depends upon a precise understanding of how these drugs interact with the cardiovascular system. It also requires a clear recognition of the different pharmacological profiles displayed by individual members of the same class of drugs. PMID- 2897904 TI - Breast feeding-induced effects on plasma gastrin and somatostatin levels and their correlation with milk yield in lactating females. AB - Maternal gastrin and somatostatin levels have been shown to be influenced during suckling in dogs and pigs. The present study was performed to investigate whether the levels of gastrin and somatostatin are influenced by breast feeding in lactating women. Repeated blood samples were drawn in connection with nursing in 15 females and plasma levels of gastrin and somatostatin were measured by radioimmunoassay. Gastrin levels rose significantly (P = 0.01) within two minutes after onset of suckling. Somatostatin levels either decreased or increased as an effect of breast feeding. The direction of the change was correlated to the pre suckling somatostatin levels (P less than 0.01). The somatostatin level recorded 60 min after start of breast feeding was significantly lower than basal levels (P less than 0.01) indicating a long-term inhibitory effect on somatostatin secretion. The suckling-induced effect on somatostatin levels was correlated with the amount of milk ejected (Rs - 0.52, P less than 0.05). The mechanism by which suckling influences circulating gastrin and somatostatin levels is unknown, but we suggest that suckling leads to a reflex activation of the vagal nerves, which influence the release of these hormones from the stomach. The size of the gastrointestinal tract is increased during pregnancy and lactation, illustrating that the maternal digestive capacity is adapted to the high demand for energy intake occurring during lactation. We speculate that the suckling stimulus enhances gastric functions by influencing the release of gastrin and somatostatin, which stimulate and inhibit gastric functions and growth, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897903 TI - Beta-blockers and calcium antagonists in angina pectoris. The potential role of combination therapy. AB - In coronary heart disease, beta-blockers are beneficial because they limit the increase in heart rate and blood pressure during exercise, and calcium antagonists are useful because they reduce myocardial oxygen demand. Many different pharmacological combinations of a beta-blocker and a calcium antagonist are possible, and beta-blockade may ameliorate reflex tachycardia induced by peripheral vasodilatation due to calcium antagonists, therefore enhancing the benefit. Studies have shown that combination therapy with propranolol and nifedipine, verapamil or diltiazem has greater antianginal efficacy based on symptomatic and objective assessment than either agent alone. A similar result has been reported for nifedipine or verapamil combined with atenolol. In combination, atenolol and nifedipine did not depress cardiac output or change the left ventricular ejection fraction (LVEF) at rest. During exercise atenolol alone resulted in a reduced LVEF response in most patients but the combination did not adversely affect left ventricular function. Nifedipine alone did not significantly change LVEF. When verapamil was combined with atenolol, resting ejection fraction fell, indicating a deterioration in cardiac function. Nifedipine and propranolol combined do not change heart rate significantly. Verapamil and atenolol both reduce resting heart rate and their combination has a greater effect; a combination of propranolol and diltiazem also reduces heart rate to a similar extent. Caution is therefore warranted when prescribing the latter 2 combinations. An increase in side effects can be expected with combination regimens compared with monotherapy; but with the nifedipine-atenolol combination the calcium antagonist can alleviate beta-blocker-induced effects by its vasodilator effect, and beta-blockers may ameliorate nifedipine-induced palpitations and flushing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897906 TI - Neuroendocrine findings in the schizophrenias. AB - A host of abnormalities have been found in responses to neuroendocrine challenges in the schizophrenias. Some, such as dexamethasone suppression, may be associated with pharmacokinetic differences in the handling of agonists or may represent a contamination of a schizophrenic population by patients with affective disorders. Other abnormalities, such as the growth hormone response to thyrotropin-releasing hormone and to luteinizing hormone-releasing hormone in adolescents but not in adults, may reflect developmental changes interacting with disease processes. Still other abnormalities may be more directly reflective of different disease processes: a rapidly neuroleptic-responsive and good-prognosis psychotic disorder appears to be associated with blunted thyrotropin response to thyrotropin releasing hormone and a blunted growth hormone response to apomorphine; a relatively drug-responsive psychotic disorder whose response requires several weeks of neuroleptic treatment appears to be associated with an excessive growth hormone response to apomorphine. The neuroendocrine windows for viewing brain function in the schizophrenias still permit indistinct images of the processes that modulate their release. Nevertheless, the images may provide important clues to the biopathology underlying these diseases. PMID- 2897905 TI - Enzymatic and structural modifications of mitochondrial NADH-ubiquinone reductase with autolysis as experimental model. AB - Complex I (nicotinamide adenine dinucleotide-ubiquinone reductase) is a complex enzyme system located in the inner mitochondrial membrane. It has the ability to catalyze several different enzymatic reactions in electron transport, and is known to be one of the respiratory chain components most sensitive to ischaemia. Mitochondria and two complexes I (complex IA and complex IB) were isolated from normal and ischaemic myocardial tissue. Enzymatic activities, polypeptide composition, as well as other components such as non-haem iron, acid-labile sulphur and ubiquinone, were determined. The results indicated that complex IB reflected the enzymatic changes in the mitochondria during myocardial ischaemia, but complex IA did not. The lesion that resulted from ischaemia was localised as altered enzymatic activities due to a different polypeptide composition, as well as loss of ubiquinone and non-haem iron from complex IB. PMID- 2897907 TI - Neuroendocrine aspects of attention deficit hyperactivity disorder. AB - This article summarizes the existing neuroendocrine literature and reports the growth hormone response to stimulation with L-dopa and clonidine in male children and adolescents with attention deficit hyperactivity disorder. Because growth hormone secretion is regulated by monoamine neurotransmitters, hyposecretion of growth hormone may reflect generalized changes in the neurochemical substrate of this disorder. With refinement, these neuroendocrine challenge tests may become unique biologic markers in identifying attention deficit hyperactivity disorder in children and adolescents. PMID- 2897908 TI - Endocrine changes in Alzheimer's disease. AB - In conclusion, at present, no consistent endocrine abnormalities can be detected in patients suffering from Alzheimer's disease. However, assessment of neuroendocrine function might help identify subpopulations of patients with particular neurotransmission abnormalities who are likely to benefit from a specific pharmacologic strategy. For example, patients in whom cholinomimetic drugs produce the greatest elevation in plasma cortisol concentration appear to derive the most symptomatic benefit from these drugs. PMID- 2897909 TI - The endocrinology of anorexia nervosa and bulimia nervosa. AB - Considerable evidence exists of hypothalamic dysfunction in patients with anorexia nervosa and bulimia nervosa. This dysfunction is reflected in disturbances of endocrine function including abnormalities of gonadotropin, growth hormone, and corticotropin-releasing hormone secretion. Whereas these disturbances are generally reversed with nutritional rehabilitation and weight restoration, it is not evident to what extent nutritional factors are the primary etiology or whether they unmask an otherwise existing but compensated central disturbance. Similarly, endocrine disturbances may be a final common pathway in which disturbances of diet, weight, activity, stress, and mood as well as hypothalamic dysfunction are expressed. PMID- 2897910 TI - Prolactin and neuroleptic drugs. AB - Serum prolactin is reliably elevated by the antipsychotic drugs. Prolactin levels have been followed in psychotic patients during the use of these drugs as an indicator of underlying pathophysiology or as a reflection of drug activity. Considerable research is underway to elucidate further the potential clinical and research utility of the prolactin response to neuroleptic drugs. PMID- 2897911 TI - Effects of psychotropic medications on hypothalamic-pituitary-adrenal regulation. AB - The psychotropic medications reviewed in this paper have widespread clinical applicability in psychiatry and other branches of medicine. These drugs clearly can alter peripheral regulation of hypothalamic-pituitary-adrenal axis hormones. In general, psychotropic medications when administered acutely have a tendency to increase the output of both adrenal and pituitary hormones associated with the axis; the benzodiazepines appear to be the exception and indeed may decrease axis activity. Psychotropic agents may also alter the results of the dexamethasone suppression test as currently used in psychiatry, since they alter the neurotransmitters that regulate corticotropin-releasing hormone secretion and also because they may change the severity of the underlying pathophysiology. Withdrawal of these drugs after long-term administration may cause an elevation of these hormones, potentially increasing the false-positive rate of the dexamethasone suppression test and other neuroendocrine tests. PMID- 2897912 TI - Accelerated onset of non-depolarizing neuromuscular blocking drugs: pancuronium, atracurium and vecuronium. A comparison with succinylcholine. AB - The time of onset and degree of neuromuscular blockade (NMB) in 80 anaesthetized patients, following either a single bolus injection of pancuronium 0.95 mg kg-1, atracurium 0.53 mg kg-1 or vecuronium 0.07 mg kg-1, or divided doses of pancuronium 0.15 mg kg-1, atracurium 0.07 mg kg-1 or vecuronium 0.01 mg kg-1 administered 3 min or 5 min before the second dose of pancuronium 0.08 mg kg-1, atracurium 0.46 mg kg-1 or vecuronium 0.06 mg kg-1, were determined and compared to the same parameters measured following succinylcholine administration (1 mg kg 1). The time to maximum NMB (100%) following the administration of succinylcholine was 58.1 +/- 5.3 s, whereas the time to maximum NMB (100%) following a single bolus injection of either pancuronium, atracurium or vecuronium was 130.6 +/- 22.2, 93.0 +/- 6.4, 127.5 +/- 13.0 s, respectively. These values for time to maximum NMB are significantly longer than the time required for succinylcholine to achieve maximal blockade. The time to attain maximum NMB following divided doses of pancuronium, atracurium or vecuronium separated by 3 min decreased significantly to 77.9 +/- 4.3, 77.5 +/- 7.6, 89.0 +/ 8.6 s, respectively. However, when the two doses of drug were separated by 5 min, only small, non-significant further decreases occurred in the time required to achieve maximum blockade. Although the time to maximum NMB following divided doses of pancuronium, atracurium or vecuronium is significantly longer than that for succinylcholine, divided dosing significantly decreases the time required to reach maximal NMB. PMID- 2897913 TI - Effect of biliary obstruction on muscle relaxation with vecuronium. AB - Vecuronium bromide was used as a muscle relaxant in 30 patients undergoing biliary surgery. Ten patients had biliary obstruction, 10 patients without biliary obstruction were elderly (78 +/- 1.2 yrs; mean +/- SEM) and 10 patients without biliary obstruction were young or middle-aged (35 +/- 3.0 yrs). The muscle response to ulnar nerve stimulation was measured electromyographically. The results indicate that the neuromuscular blocking effect of vecuronium is significantly prolonged in patients with biliary obstruction. The mean total dose of vecuronium was lower in the patients with biliary obstruction (1.2 +/- 0.1 micrograms kg-1 min-1) than in the elderly patients (1.7 +/- 0.2 micrograms kg-1 min-1) and young patients (2.0 +/- 0.2 micrograms kg-1 min-1; P less than 0.05). There were no statistically significant differences in the distribution half lives or in the distribution volumes of vecuronium between the groups. PMID- 2897914 TI - Heart rate reduction--a mechanism of benefit? PMID- 2897915 TI - Effect of ST-567 (a specific bradycardiac agent) in patients with unstable angina and myocardial infarction. AB - At the time of hospital admission the distinction between reversible ischaemia (angina) and myocardial damage (infarction) is often difficult. Thus it would be advantageous when a similar therapeutic approach could be used in both conditions. Alinidine was given intravenously (10-40 mg) to 24 patients with unstable angina. Heart rate decreased as well as systolic and mean arterial pressure, while stroke volume remained constant. One patient developed heart failure due to an overdose of alinidine (80 mg) in combination with a beta blocker. Furthermore, alinidine was administered in 32 patients with acute myocardial infarction, 23 of these suffered from heart failure. Similar haemodynamic effects were observed while a rise of pulmonary capillary wedge pressure occurred in two patients only. Alinidine appears to be a safe drug for reduction of heart rate in patients with unstable angina and acute myocardial infarction. Further studies to verify the clinical benefit of such a treatment are required. PMID- 2897916 TI - Specific bradycardic agents--a novel pharmacological class? AB - Data have been reviewed and presented which suggest that substances from two different chemical groups, congeners of alinidine and falipamil, respectively, can be described as representatives of a novel and distinct pharmacological class: specific bradycardic agents (SBAs). They are characterized by a slowing of the sinus rate within physiological limits as the prominent cardiovascular effect. Involvement of alpha-adrenoceptors, beta-adrenoceptors and cholinergic receptors as mediators of the bradycardic effects have been excluded. Experiments in isolated atrial preparations suggested that drugs of the same type as alinidine or as falipamil have a similar mode of rate lowering action which is different from that of Ca-channel blockers: low external Ca2+ increased and low Na+ as well as high K+ decreased the bradycardic effect of SBA; verapamil behaved in the opposite way. Combination of different SBAs did not result in excessive additive rate-lowering effects; in contrast, addition of verapamil to maximally acting concentrations of SBAs resulted in a further significant reduction in rate. SBAs were much more potent in reducing spontaneous sinus rate than in reducing BaCl2 induced automaticity, whereas Ca-channel blockers behaved in the opposite way. Differences in the cardiovascular profile against other drugs with rate lowering effects have been pointed out: beta-adrenoceptor blocking agents more markedly decrease contractility and Ca-channel blocking agents more markedly decrease contractility, slow down AV conduction and have vasorelaxing properties.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897917 TI - Treatment of the elderly hypertensive: a clinical perspective. AB - The negative effects of high blood pressure on longevity and health in the elderly are considerable. Despite this fact physicians still tend to be reluctant when it comes to exposing elderly hypertensives to antihypertensive treatment. To some extent this cautious attitude can be rationalized because cardiovascular homeostasis becomes less effective with increasing age, particularly in hypertension. Over the past decade, however, several controlled trials have demonstrated a favourable benefit/hazard ratio with respect to the effects of antihypertensive treatment on cardiovascular prognosis in elderly hypertensives. The results of these trials are briefly reviewed, followed by a more extensive report on the trial conducted by the European Working Party on Hypertension in the Elderly (EWPHE). The implications for practice are considered with respect to different classes of hypotensive drugs. Thiazides--with potassium sparing adjuvants--despite their biochemically untoward effects are recommended as the treatment of first choice in view of the trial results. The remainder (beta blockers, calcium channel blockers, ACE inhibitors, ketanserin) are still in the competing stage, although there may be clarification in the near future in terms of subjective side-effects and ancillary properties. PMID- 2897918 TI - Blockade of alpha 2-adrenoceptors by 1-(2-pyrimidinyl)-piperazine (PmP) in vivo and its relation to the activity of buspirone. AB - The effect of 1-(2-pyrimidinyl)-piperazine (PmP) and the parent drug, buspirone in counteracting the behavioral and biochemical effects of clonidine were evaluated in the rat. Intraperitoneal or oral administration of PmP, buspirone and yohimbine, but not of prazosin, antagonized the slowing of gastrointestinal motility induced by subcutaneous clonidine (0.1 mg/kg). The doses that inhibited the effect of clonidine on the transit time by 50% were 0.5 mg/kg i.p. and 0.7 mg/kg p.o. for PmP, 7 mg/kg i.p. and 9 mg/kg p.o. for buspirone and 0.5 mg/kg i.p. for yohimbine. PmP (0.5 mg/kg) did not block the antitransit effect of clonidine when administered by intracerebroventricular injection. The antitransit effect of a low dose of morphine (0.05 mg/kg i.p.) was not blocked by PmP (2 mg/kg i.p.). The prolongation of the hexobarbital-induced loss of the righting reflex that occurs after clonidine (0.25 mg/kg i.p.) administration was inhibited by pretreatment with PmP (0.1-2 mg/kg p.o.) or yohimbine (1 mg/kg i.p.) but not by pretreatment with prazosin (2 mg/kg i.p.). Buspirone (1-20 mg/kg) also reduced the effect of clonidine after oral administration, with a maximal effect at 5 mg/kg, whereas the same dose administered i.v. had less effect. PmP (2 mg/kg) and buspirone (15 mg/kg) raised the levels of total 3-methoxy-4-hydroxyphenylgycol (MHPG) in rat cerebral cortex, and prevented the decrease in MHPG induced by clonidine. These findings show that buspirone, in doses at which it is active as an anxiolytic, suppresses the central and peripheral effects of clonidine. This action occurs through alpha 2-adrenoceptors and is mediated primarily by the metabolite, PmP. PMID- 2897919 TI - Elimination of Na+ and GTP regulation of alpha 2-adrenoceptor-agonist interactions in rat kidney membranes by 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid (DIDS). AB - Pretreatment of rat kidney membranes with 4,4'-diisothiocyano-2,2'-stilbene disulfonic acid (DIDS) did not affect the Bmax but reduced the affinity of the receptors for antagonist by less than 2-fold. However, such treatment reduced the affinity of the receptors for agonist by several fold by preventing the formation of agonist-receptor-Gi-protein complex. The modulatory effects of GTP and Na+ on alpha 2-adrenoceptor-agonist interactions were also abolished. These results suggest that DIDS acts at multiple sites on alpha 2-adrenoceptor-adenylate cyclase complex. PMID- 2897920 TI - Activation of the 5-HT1A receptor subtype increases rat plasma ACTH concentration. AB - Serotonergic (5-HT) neuronal pathways regulate the release of adrenocorticotropin hormone (ACTH) from the pituitary gland probably through the action of hypothalamic corticotropin-releasing hormone (CRH). 8-Hydroxy-2-(di-n propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist, dose dependently (0.016-3 mg/kg s.c.) increased rat plasma ACTH concentration. This response was blocked stereoselectively by (-)-pindolol, known to have 5-HT1 antagonist properties, but not by (+)-pindolol, beta 1-, beta 2- or alpha 1 adrenoceptor, dopamine, muscarinic, 5-HT2 or 5-HT3 receptor antagonists. Similar increases of plasma ACTH were induced by other 5-HT1A receptor ligands (buspirone, ipsapirone and gepirone). These results suggest that activation of the 5-HT1A receptor induces the secretion of ACTH from the rat pituitary gland. PMID- 2897921 TI - Identification of B2 bradykinin binding sites in guinea-pig brain. PMID- 2897922 TI - The acute effects of methylenedioxymethamphetamine on dopamine release in the awake-behaving rat. AB - The effects of the recently classified Schedule I amphetamine analog, 3,4 methylenedioxymethamphetamine [+/-)-MDMA) on caudate and nucleus accumbens dopamine release and metabolism were studied by in vivo voltammetry and HPLC with electrochemical detection. Monitored over a 3 h period, the magnitude of increase in dopamine release and the onset of effect were dose-dependent and similar for both brain areas following the 2.5 and 5 mg/kg dose of the drug. However, responses were different for these brain regions using 10 mg/kg of MDMA; the magnitude of increase was greater and the onset of effect more immediate in caudate. Analysis of dopamine and DOPAC tissue content in both caudate and nucleus accumbens verified the voltammetry results. This study provides the first evidence that MDMA induces dopamine release in vivo and that this effect is region, time- and dose-dependent. PMID- 2897923 TI - Inhibition of post-decapitation convulsions in the rat by dibenzothiepin neuroleptics via alpha 1-adrenoceptor blockade. AB - The mechanisms involved in inhibitory effects of isofloxythepin, a newly synthesized dibenzothiepin neuroleptic, on post-decapitation convulsions were studied in rats. Isofloxythepin (0.05-2.0 mg/kg s.c.) inhibited post-decapitation convulsions in a dose-dependent manner as shown by the decrease in the incidence and the shortening of the duration of convulsions. The convulsions were also inhibited by oxyprothepin, zotepine or chlorpromazine but not by haloperidol. Prazosin and bunazosin, both alpha 1-adrenoceptor antagonists, suppressed the post-decapitation convulsions but a non-selective alpha 2-adrenoceptor agonist, tolazoline, was without effect. The convulsions were inhibited dose dependently by clonidine, an alpha 2-adrenoceptor agonist, but were prolonged in duration by yohimbine, an alpha 2-adrenoceptor antagonist. Yohimbine antagonized the inhibitory effects of isofloxythepin, prazosin and clonidine. The noradrenaline induced contraction of rat vas deferens was inhibited by isofloxythepin, prazosin or chlorpromazine. Isofloxythepin bound to alpha 1-receptors as did chlorpromazine in the rat brain cortex. The results imply that post-decapitation convulsions seem to be inhibited by a block of postsynaptic alpha 1 adrenoceptors, enhanced by a block of presynaptic alpha 2-adrenoceptors and reduced by isofloxythepin via the blocking of postsynaptic alpha 1-adrenoceptors. The convulsions thus could serve as a good model for studying the actions of drugs on the central nervous system alpha-adrenoceptors. PMID- 2897924 TI - Climbing and stereotyped behaviours in mice require the stimulation of D-1 dopamine receptors. AB - Apomorphine-induced climbing and sniffing behaviours in mice were antagonize by low doses of SCH 23390 and metoclopramide. The selective D-2 dopamine receptor agonists, LY 171555 and RU 24926, and some other dopamine agonists (piribedil, lergotrile, bromocriptine) exerted only inhibitory effects on spontaneous behaviours. The selective D-1 dopamine receptor agonist, SK&F 38393, did not modify the climbing score but increased the sniffing and decreased the gnawing scores compared to the scores of control mice. Typical climbing and stereotyped behaviours were produced by the combination of SK&F 39383 with LY 171555, RU 24926 or with the other dopamine agonists tested. These data suggest that the stimulation of D-1 dopamine receptors is required for the induction of climbing and stereotyped behaviours in mice. PMID- 2897925 TI - Scopolamine modulates apomorphine-induced behavior in rats treated with haloperidol or SCH 23390. AB - In acute experiments, scopolamine (1.0 mg/kg) potentiated apomorphine stereotypy and inhibited the antistereotypic effect of both haloperidol (0.5 mg/kg) and SCH 23390 (0.2 mg/kg). Daily administration of either haloperidol (0.5 mg/kg) or SCH 23390 (0.2 mg/kg) for 3 weeks produced enhanced stereotypic responses to apomorphine. Co-administration of scopolamine (1.0 mg/kg) with haloperidol or SCH 23390 significantly reduced the behavioral supersensitivity produced by haloperidol or SCH 23390 alone. It is suggested that both D-1 and D-2 dopamine receptors are linked to a cholinergic mechanism. PMID- 2897926 TI - Effect of ammonium chloride on subcellular distribution of lysosomal enzymes in human fibroblasts. AB - Three subcellular fractions enriched in lysosomal enzyme activities have been isolated recently from human cultured fibroblasts with Percoll gradients: the dense lysosomes (DL), light lysosomes (LL), and light membranous vesicles (LM). They were shown to have different morphological, cytochemical, biochemical, and immunological properties. We now report on the dramatic but different effects of a primary amine, NH4Cl, on these subfractions. The lysosomes, as detected with a specific ultrastructural cytochemical stain for the lysosomal enzyme, arylsulfatase A, were swollen significantly in all these fractions, increasing their volumes by 64% (DL), 53% (LL), and 95% (LM), respectively. When arylsulfatase A enzyme activity was monitored, about half of the DL content was diverted to the LL. However, when newly synthesized arylsulfatase A enzyme protein was monitored with metabolic labeling and immunoprecipitation, about 80% of the enzyme protein was depleted from both the DL and LL. In contrast, neither the enzyme activity nor the newly synthesized enzyme protein of arylsulfatase A was greatly altered in the LM fraction by the treatment. Since primary amines caused newly synthesized lysosomal enzymes to diverge from the lysosomal route to a secretory pathway, it was deduced that (i) the LM fraction corresponded to a prelysosomal compartment whose lysosomal enzyme content was not affected by the amine and was thus proximal to the point of diversion between the secretory and lysosomal pathways; (ii) the LL and DL fractions were distal to the point of diversion since both fractions were depleted of their newly synthesized lysosomal enzyme; and (iii) the sorting of newly synthesized lysosomal enzyme may be different from that of the preexisting pool of the same enzyme since the LL fraction was depleted of its newly synthesized enzyme protein while accumulating excessive enzyme activity. PMID- 2897927 TI - Immunogenicity of specific Bordetella pertussis surface antigens in diphtheria tetanus-pertussis (DTP) vaccines. AB - The predominant causative organism of whooping cough in Australia is of a serotype which has normally been associated overseas with unvaccinated communities. Australian DTP vaccines pass the statutory mouse test for Bordetella pertussis potency but this test is now believed to be relatively insensitive to certain factors, especially the major type-specific agglutinogens, which are presumably also important in the human host-parasite relationship. Because endemic B. bronchiseptica infections make some laboratory animals unsatisfactory for testing B. pertussis agglutinin responses, we have developed a test in which young farm sheep were immunized with vaccines. Type-specific agglutinins in their sera were assayed after absorption of non-specific agglutinins by suspensions of selected bordetella strains. Three well-reputed European DTP vaccines and two recent batches of Australian DTP vaccine were tested and compared thus. All evoked significant agglutinin responses to the main agglutinogens. PMID- 2897928 TI - The nature of posterior hypothalamic projections to cardiorespiratory centers in the brainstem. AB - Focal electrical stimulation of the midlateral posterior hypothalamus in the rat produces rapid shallow respiration accompanied by a rise in arterial blood pressure. Stimulation of presumably intrinsic neurons only by glutamate induces slower deeper respiration associated with a fall in blood pressure. PMID- 2897929 TI - Haplotypes of thalassaemic families from the Po river delta: importance for prenatal diagnosis of beta-thalassaemia. AB - The beta globin haplotypes, corresponding to 50 normal and 50 thalassaemic chromosomes, were determined in 25 families from the Po river delta area who had beta thalassaemia. The haplotypes were obtained by studying the familial segregation of 6 restriction fragment length polymorphisms of the beta globin gene cluster. The results show an almost exclusive presence of 3 haplotypes linked to the beta thalassaemia chromosomes of this area: haplotype I, II and IX according to Orkin's classification. It is therefore possible that only two thalassaemic mutations are present. A wider variety of haplotypes was found to be linked to normal chromosomes. Prenatal diagnosis, by the analysis of polymorphic sites (the 6 plus one other) was possible in 92% of the cases. The probable high homogeneity of the molecular mutations makes the use of specific oligonucleotides practical and applicable to prenatal diagnosis. PMID- 2897930 TI - Y-body study in bone marrow precursors, peripheral blood cells and alveolar macrophages for demonstration of haemopoietic engraftment in allogeneic bone marrow transplantation. AB - The value of Y-body study for assessment of haemopoietic engraftment was analyzed in 50 consecutive patients submitted to allogeneic bone marrow transplantation (BMT) (sex-matched in 28 cases, sex-mismatched in 22). The study was performed weekly on bone marrow and peripheral blood smears in all cases, and alveolar macrophages were also studied in 15 patients in whom bronchoalveolar lavage was carried out because of concurrent respiratory disturbances. The analysis was performed blindly by 2 independent observers. In both sex-matched and sex mismatched cases there was an absolute concordance between recipient and donor Y body results, as well as with the simultaneous cytogenetic study. The engraftment of erythroid and granulopoietic lines was documented at day +14 in all cases of sex-mismatched BMT, whereas megakaryocyte and lymphocyte take was demonstrated at d +21. On the other hand, the results from alveolar macrophages were in accordance with those obtained in the simultaneous study of bone marrow precursors after BMT. The above results indicate that Y-body analysis is a simple and useful tool for the demonstration of bone marrow take in sex-mismatched BMT. PMID- 2897931 TI - [Antihistaminic antiallergy preparations in the quinuclidine series]. PMID- 2897932 TI - [Effect of carbidine, sulpiride and haloperidol on levels of monoamines and their metabolites in the brain structures of rats]. AB - Haloperidol (1 mg/kg) was shown to increase significantly the dopamine (DA) turnover in n. accumbens and striatum and to a lesser degree in frontal cortex and hypothalamus of the rat brain; to decrease the noradrenaline content in hypothalamus. Sulpiride (50 mg/kg) slightly increased DA turnover in striatum and hypothalamus and lowered the serotonin (5-HT) content in frontal cortex. Carbidine (25 mg/kg) was found to increase DA turnover in frontal cortex, striatum and hypothalamus to a greater degree than haloperidol; 5-HT turnover was increased in all the cerebral regions. The results obtained indicated that the atypical neuroleptic drug carbidine exerts the predominant effect on the frontal cortex, the serotoninergic component being clearly pronounced. PMID- 2897933 TI - [Neuropharmacology of the autonomic vestibular syndrome]. AB - It was found during studies on man and experiments on animals that various neuromediator systems of the organism (M-cholinergic, H1-histaminergic, dopaminergic, and opioidergic) are involved in the genesis of VVS. In addition, animal experiments showed that of great importance in the process are different regulatory peptides, in particular, substance P and beta-endorphin. The findings indicate that some neuropeptides may be used in the future in man for VVS prevention. At neuronal level the role of opioid peptides in realization of vestibulovegetative reactions is decoded and a number of possible mechanisms of their action is established. The study of the human hormonal status in VVS revealed complex neuroendocrine changes occurring in the organism. Based on the knowledge of some neurohormonal and neurochemical mechanisms of VVS pathogenesis, a new drug prevention and therapy of seasickness was proposed, efficacy of opioid antagonists naloxone and nalorphine was shown. PMID- 2897934 TI - [Influence of piracetam on the effects of narcotic analgesics and opioid peptides]. AB - Piracetam possesses some properties not related to the nootropic activity. The purpose of the work was to study piracetam influence on effects of narcotic analgesics and opioid peptides at intracerebroventricular administration. In experiments on cats it was found that piracetam in a dose-dependent way prevented the emetic effect of morphine and leu-enkephalin. In experiments on rats (tail flick test) piracetam was shown to be able of blocking the analgesic effect of fentanyl. Experiments on the study of the anticataleptogenic effect of piracetam also showed antagonism between piracetam and agonists of opioid receptors. Thus, it was shown on a number of models that piracetam exhibits antagonistic properties with respect of opioid peptides and narcotic analgesics. PMID- 2897935 TI - [Characteristics of dimedrol, pipolfen and suprastin absorption from the small intestine of rats in systemic anaphylactic shock]. AB - It was shown by the in situ method that absorption of dimedrol, pipolphen and suprastine from the small intestine of the rats immunized parenterally with ovalbumin against the background of intravenous administration of the resolving dose of ovalbumin significantly decreased in connection with the formation in the immunized rats of antiovalbumin antibodies. Administration of euphylline simultaneously with the resolving dose of ovalbumin to the immunized rats partially normalized absorbability of all three drugs. PMID- 2897936 TI - Suppression of clofibrate-induced peroxisome proliferation in rat liver by nicardipine, a calcium antagonist. AB - In vivo administration of nicardipine, nifedipine and diltiazem, known as calcium antagonists, suppressed the clofibrate-evoked induction of activities of peroxisomal enzymes, such as the peroxisomal fatty acyl-CoA oxidizing system and carnitine acetyltransferase. The inhibition activity of nicardipine with respect to clofibrate induction of the two enzyme systems was 62 and 33%, respectively. Induction of the peroxisomal bifunctional protein, enoyl-CoA hydratase/3 hydroxyacyl-CoA dehydrogenase, by clofibrate was suppressed about 60% by nicardipine on analysis of the hepatic protein composition by SDS-polyacrylamide gel electrophoresis. Other drugs also exhibited similar inhibitory activity. These results provide the first demonstration of calcium antagonists, e.g. nicardipine, nifedipine and diltiazem, acting as inhibitors of peroxisome proliferation in animals. Such drugs might become useful as tools for elucidating the mechanism of peroxisome proliferation and for determination of the pathological conditions under which peroxisomal function is impaired. PMID- 2897937 TI - Structural requirements of choline derivatives for 'conversion' of pneumococcal amidase. A new single-step procedure for purification of this autolysin. AB - Tertiary amines appear to be the minimal structure needed to convert in vitro the inactive form (E-form) of pneumococcal amidase to the catalytic active form (C form). Diethylethanolamine was one of the compounds that converted the E-form, a finding that has been used successfully to develop an affinity chromatography system in DEAE-cellulose for the rapid and efficient purification of lytic enzymes of pneumococcus and its bacteriophages. PMID- 2897938 TI - [Cytological method in the prevention and early diagnosis of cancer]. PMID- 2897939 TI - Eicosanoids as pluripotential modulators of pancreatic islet function. AB - Eicosanoids both negatively and positively modulate glucose-induced insulin secretion. Although the identity of the positive modulator is uncertain, the negative modulator appears to be prostaglandin E2 (PGE2), because 1) glucose stimulates PGE2 synthesis from islet cells; 2) exogenous PGE2 inhibits glucose induced insulin secretion; 3) inhibition of beta-cell PGE2 synthesis increases glucose-induced insulin secretion, and this increase is reversed by exogenous PGE2; and 4) PGE2 binds to specific beta-cell receptors that are coupled to inhibitory regulatory components of adenylate cyclase whose activation decreases cAMP levels. Other possible regulatory effects of eicosanoids on islet function include modulation of islet blood flow and its immune responsiveness. From these considerations, the perspective is offered that eicosanoids are pluripotential modulators of islet function. PMID- 2897940 TI - Factors in development of diabetic neuropathy. Baseline analysis of neuropathy in feasibility phase of Diabetes Control and Complications Trial (DCCT). The DCCT Research Group. AB - The Diabetes Control and Complications Trial (DCCT) is a multicenter randomized clinical trial studying the effect of intensive insulin therapy on the early vascular and neurological complications of insulin-dependent diabetes mellitus (IDDM). During the feasibility phase of the DCCT, baseline neurological histories, physical examinations, and laboratory measurements of somatic and autonomic nerve function were obtained in 278 well-characterized IDDM subjects. Subjects were free of advanced complications, including the presence of peripheral or autonomic neuropathy sufficiently severe to require treatment. Analyses of the cross-sectional data reveal that clinically detectable peripheral neuropathy was present in 39% of the subjects. The presence of clinical neuropathy correlated with greater age, longer duration of IDDM, and male gender. The somatic and autonomic test results confirm the relationship between age, diabetes duration, and male gender and diabetic neuropathy. These results support an effect of age and gender on the development of diabetic complications. PMID- 2897941 TI - The psychiatric management of the globus syndrome. AB - Controversy surrounding the term "globus hystericus" points up the historical dichotomy between organic disease and conversion disorder that has hampered the understanding of this syndrome. Regardless of its sometimes incapacitating nature, there is little information in the literature regarding the treatment of globus when an organic cause cannot be established. Regarding the syndrome as psychosomatic in nature, rather than merely hysterical, we suggest the need for an integrated treatment approach. A case study is utilized to illustrate a model for psychiatric management of the globus syndrome. In this model, pharmacologic and psychotherapeutic interventions are integrated into a comprehensive, biopsychosocial treatment plan. Each aspect of the model is reviewed and discussed. PMID- 2897942 TI - An 80-bp cis-acting regulatory region controls cAMP and development regulation of a prestalk gene in Dictyostelium. AB - We have analyzed an 80-bp region containing the cis-acting sequences necessary for regulation of the Dictyostelium discoideum prestalk gene pst-cathepsin at the appropriate stage during multicellular development and in response to cAMP in single-cell culture. The region lies between approximately -280 and -200 bp upstream from the Cap site and contains two intertwined G/C-rich sequences, including a palindromic sequence and a direct repeat of the 3' portion of the palindrome. In a previous set of experiments, we showed that the direct repeat, or G-box, is important in the regulation of pst-cath expression. In this paper, we use a series of nested internal deletions to define other regions within the promoter required for cAMP and developmental expression, to further examine the importance of the two G-boxes, and to examine the functional relationship of the G-boxes with respect to the other regulatory sequences. Analysis of the expression of these constructs in transformed cells showed that both the 5' portion of the palindrome and the two G-boxes are required for promoter function and are capable of developmentally regulating pst-cath expression. An A/T-rich sequence located 5' to the G/C-rich sequence is also essential for maximal expression, whereas insertion of a linker 5' to this region suggests the presence of a negative element functional during multicellular development. The spacing between the G-box sequences proved to be important for the full induction of gene expression. Constructs containing the G-boxes at wild-type spacing or closer show wild-type or near wild-type levels of expression, whereas expansion of the region between the G-boxes leads to a substantial drop in the level of gene expression in response to cAMP. Insertion of an oligonucleotide containing one of the G boxes and surrounding sequences can partially complement deletions in which this region has been removed. Analysis of the expression of the cassette constructs, in some cases, revealed significant differences in the quantitative level of expression under the two developmental conditions. This suggests that there are either qualitative or quantitative differences in the factors controlling the expression of this gene under these two conditions. PMID- 2897944 TI - Effects of psychotropic drugs on memory: Part 2. PMID- 2897943 TI - Temporal and spatial relationships between segmentation and homeotic gene expression in Drosophila embryos: distributions of the fushi tarazu, engrailed, Sex combs reduced, Antennapedia, and Ultrabithorax proteins. AB - The specification of segment number and identity in the Drosophila embryo requires the activity of several classes of genes that may be grouped according to the array of pattern elements that they control. Double-label immunofluorescence was used to simultaneously localize the products of genes representative of the pair-rule segmentation class (fushi tarazu), the segment polarity class (engrailed), and the homeotic class (Sex combs reduced, Antennapedia, and Ultrabithorax) of pattern-regulating genes. The temporal order of appearance of each class of proteins and the precise spatial relationships between the products of the different genes are described with single-cell resolution. Boundaries of gene expression, particularly the parasegmental boundaries, are established by early-acting genes such as fushi tarazu and subsequently respected by the expression patterns of later appearing gene products such as engrailed and Ultrabithorax, suggesting regulatory relationships between certain pairs of genes. In addition, the dynamic transitions observed in spatial relationship among the Sex combs reduced, Antennapedia, and Ultrabithorax homeotic protein patterns during the early period of embryogenesis may reflect cross-regulatory interactions among these genes. Finally, some cells contain a single homeotic product, whereas other cells simultaneously contain several, suggesting that certain cells may be determined by the combinatorial action of homeotic genes. PMID- 2897945 TI - Polymorphic restriction sites of type II collagen gene: their location and frequencies in the Finnish population. AB - Restriction fragment length polymorphism (RFLP) of the cartilage-specific type II collagen gene has been studied in the Finnish population. Two high-frequency alleles, also reported in other populations, were detected. The HindIII allele had a frequency of 0.33, and that detected with PvuII a frequency of 0.46. Both of these frequencies resembled the ones reported for other populations. Also one BamHI allele, not earlier reported, was found at a low frequency. Two other previously reported polymorphisms for BamHI and EcoRI were not detected in the Finnish population. The RFLPs showed a fair agreement with the Hardy-Weinberg equilibrium. A linkage disequilibrium was found between PvuII and HindIII markers. The alpha 1(II) collagen gene seems to be more conserved in populations of various origins than the alpha 2(I) collagen gene. These polymorphic collagen markers would be useful in linkage studies of various inherited cartilage disorders. PMID- 2897946 TI - DNA polymorphisms, identified by an X-chromosome short-arm probe L 1.28 (DXS7), in different racial groups. AB - Restriction fragment length polymorphisms of the L1.28 probe which is closely linked to X-linked disorders, retinitis pigmentosa and Norrie disease, were studied in samples from England, India and Nigeria. The frequency of the A2 allele (9-kb fragment) was 0.23, 0.55 and 0.46 in England, India and Nigeria, respectively. The differences between the English and Indian populations were highly significant. PMID- 2897947 TI - Peer review of research abstracts. PMID- 2897948 TI - Incidence of retroviruses in some Brazilian groups. AB - The prevalence of human T lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV) antibodies was evaluated in Brazil among 116 aboriginal Indians living in a pre-Amazonian region, and in 44 patients with haematological malignant disorders being treated in Rio de Janeiro. Screening for the presence of antibodies to HIV was performed routinely for 17,224 blood donors at the National Cancer Institute, Rio de Janeiro, from January 1986 to May 1987. The results demonstrated that HIV infection was not endemic among Brazilian Indians, as none of them had antibodies to HIV, in contrast with the population of Rio de Janeiro, which showed a high prevalence (0.34%) of positivity among normal individuals. In a small group of patients with haematological disease only one with acute lymphoblastic leukaemia proved to be HIV-positive, the infection having been acquired through previous blood transfusion. None of the serum samples reacted with HTLV-I, including those of 17 non-Hodgkin's lymphoma patients. HTLV-I infection does not seem to be endemic in this country, but further large scale studies are necessary, especially in patients with haematological disorders, homosexual individuals and drug users. PMID- 2897949 TI - Class II genes of miniature swine. I. Class II gene characterization by RFLP and by isolation from a genomic library. AB - Class II genes of miniature swine have been characterized by restriction fragment length polymorphism (RFLP) analysis and by analysis of a series of clones isolated from a lymphocyte genomic library. For RFLP analysis, DNA samples from three independent major histocompatibility complex homozygous lines and three intra-MHC recombinant lines were digested with a variety of restriction enzymes and analyzed in Southern blots using human cDNA probes for DP, DQ, DR, and DZ alpha genes, and DP, DQ, DR, and DO beta genes. One, or at most two, unique fragments were detected by hybridization with each of the human alpha probes tested. In contrast, multiple bands (five to six for most enzymes examined) were detected by each of the human beta probes tested, the majority of which were found to cross-react with at least three of these probes under conditions of moderate stringency. Genomic DNA from the SLAc haplotype was cloned into an EMBL 3 bacteriophage vector, and the corresponding genomic library was screened with each of these human cDNA probes. The class II genes thereby isolated from this library showed characteristics consistent with those anticipated from the RFLP analysis. Thus, unique alpha genes were obtained which showed no evidence of cross-hybridization, while beta genes showed extensive cross-hybridization and were frequently detected in the library by more than one human beta gene probe. These data are consistent with early evolutionary divergence of alpha genes, prior to mammalian speciation, and with continuing evolution of beta genes, with possible shared usage of these genes by different alpha loci. The data also imply that alpha genes can readily be assigned to loci homologous to their human counterparts, but that beta genes will require further mapping and/or sequence analysis to confirm assignments. PMID- 2897950 TI - Genetic mapping of C4 and Bf complement genes in the rat major histocompatibility complex. PMID- 2897951 TI - Evaluation of alphamethrin, a synthetic pyrethroid for insecticidal activity against mosquitoes. PMID- 2897952 TI - Congestive cardiac failure: advances in management. PMID- 2897954 TI - [A 52-year-old patient with fever, massive pericarditis exsudativa and acute mononeuritis multiplex]. PMID- 2897953 TI - Evaluation of oral administration of folic and folinic acid to prevent folate deficiency in patients with inflammatory bowel disease treated with salicylazosulfapyridine. AB - In order to evaluate the efficacy of oral administration of a pharmacological dose of folic or of folinic acid to prevent the folate deficiency in patients with inflammatory bowel disease (IBD) treated with salicylazosulfapyridine (SASP) (1g twice daily at meal times), two groups of 15 patients with IBD received 15 mg/day of folic or folinic acid for one month. In both the groups there were ten patients affected by Crohn's disease and five patients affected by ulcerative colitis. Before starting the treatment, the plasma folate and the red blood cell (RBC) folate concentrations did not statistically differ between the two groups. After one month the mean increase in RBC folate concentration was significantly greater after folinic therapy then after folic acid therapy (910 +/- 383 versus 570 +/- 212 ng/ml; p less than 0.01), while no difference was observed in the mean increase of plasma folate level (19.8 +/- 6.6 versus 18.5 +/- 5.0 ng/ml). It was concluded that: a) both folic and folinic acid could restore and enlarge the body stores of folate in patients with IBD treated with SASP, when administered at the dose of 15 mg daily for one month; b) folinic acid seems to be more efficient in enlarging the body stores of the vitamin than folic acid. PMID- 2897955 TI - Beta-adrenergic receptors in the urinary bladder of adult and developing rats. AB - Specific beta-adrenergic receptors were demonstrated in the urinary bladder of adult and developing rats, by direct tissue binding with LD [125I]-cyanopindolol (CYP). The maximum number of binding sites (Bmax) was 167 +/- 25 fmol/mg membrane protein and the dissociation constant (KD) equalled 61 +/- 33 pM. The Hill slopes of the LD [125I]-CYP binding showed a single class of noncooperative receptor sites. The rank order of potency of agonist competition for LD [125I]-CYP binding suggests that the receptors are mostly of the beta 2 subtype. Beta-adrenergic receptor density was approximately half in the first 10 days of life (Bmax 63 to 77 fmol/mg protein) compared with the older age-groups studied (Bmax 91 to 167 fmol/ng protein). On the 1st day after delivery, the calculated beta-adrenergic receptor number/bladder was 9.4, and it increased significantly with age to 2,496 in the adult rat. This is a 250-fold increase in the number of receptors/bladder, while only a 20-fold increase in membrane protein and a five- to sixfold increase in the bladder weight was observed. Thus, an age-dependent increase of beta adrenergic receptors on the cell membrane surface area occurred in the developing urinary bladder of the rat. PMID- 2897956 TI - Recurrent poststreptococcal cutaneous polyarteritis nodosa. PMID- 2897957 TI - Evaluation of continuing education in health education: the Society for Public Health Education's 1983, 1984 and 1985 mid-year scientific symposia. AB - The Society for Public Health Education's (SOPHE) first three mid-year scientific symposia were evaluated three months after each meeting with questionnaires mailed to all national SOPHE members who attended and a 10% sample of members who did not attend. 3% of SOPHE members attended the first meeting, rising to 7% and 12% in subsequent years. Persons spending their time in direct education and program planning/development and persons less active in health education professional organizations were under-represented at the meetings. About 90% of those who attended the meetings learned something that they had applied to their health education work. A third to a half had made contact with another health educator on health education business, and about one fifth had increased their participation in SOPHE affairs due to the meeting. Those who attended the mid year meetings were significantly more likely to plan attendance at the next annual meeting than those who did not attend. Over half of those polled felt that SOPHE should continue to hold mid-year meetings; most of the rest were not sure. Strengths and weaknesses of the individual meetings are discussed, as well as suggestions for improvement, topics and forums for future meetings. PMID- 2897958 TI - Pathophysiology of ADDH. PMID- 2897959 TI - Beta-adrenoceptor antagonists in neuropsychiatry: an update. AB - Although beta-adrenoceptor antagonists such as propranolol have been used in neuropsychiatry for more than 20 years, their indications, extent of efficacy, and place in therapy remain unclear. In this overview, which concentrates on the recent literature, four indications for use of the drugs are reviewed, with particular reference to efficacy, mode of action, and clinical utility. The indications are anxiety disorders, including performance anxiety; schizophrenia; aggressive behavior; and akathisia. The author concludes that beta-blockers are useful in some forms of anxiety disorder, perhaps those characterized by somatic symptoms and by performance anxiety, and that akathisia seems to be responsive to those drugs. However, the use of high doses of beta-blockers in schizophrenia remains unestablished, and insufficient data are available with respect to their use in aggressive behavior. PMID- 2897960 TI - Relapse rate and low serum neuroleptic levels in schizophrenics treated with fluphenazine: another view. PMID- 2897961 TI - Evidence that glutamic acid 49 of tryptophan synthase alpha subunit is a catalytic residue. Inactive mutant proteins substituted at position 49 bind ligands and transmit ligand-dependent to the beta subunit. AB - Glutamic acid 49 of the alpha subunit of tryptophan synthase from Escherichia coli is an essential residue since 19 mutant proteins substituted at position 49 were found previously to be inactive. Our present findings that five mutants of the alpha subunit, substituted with Asp, Lys, Ala, Phe, or Gly at position 49, bind a substrate analog normally are further evidence that glutamic acid 49 is a catalytic base. Ligands of the alpha subunit also have similar effects on site site interactions between the beta subunit and the wild type or mutant alpha subunits. These effects include inhibition of the activity of the beta subunit, reduction of the dissociation constant for D-tryptophan, and increase of the equilibrium concentration of a quinonoid intermediate formed with L-tryptophan. PMID- 2897962 TI - A homologous sequence between H+-ATPase (F0F1) and cation-transporting ATPases. Thr-285----Asp replacement in the beta subunit of Escherichia coli F1 changes its catalytic properties. AB - A sequence of 10 amino acids (I-C-S-D-K-T-G-T-L-T) of ion motive ATPases such as Na+/K+-ATPase is similar to the sequence of the beta subunit of H+-ATPases, including that of Escherichia coli (I-T-S-T-K-T-G-S-I-T) (residues 282-291). The Asp (D) residue phosphorylated in ion motive ATPase corresponds to Thr (T) of the beta subunit. This substitution may be reasonable because there is no phosphoenzyme intermediate in the catalytic cycle of F1-ATPase. We replaced Thr 285 of the beta subunit by an Asp residue by in vitro mutagenesis and reconstituted the alpha beta gamma complex from the mutant (or wild-type) beta and wild-type alpha and gamma subunits. The uni- and multisite ATPase activities of the alpha beta gamma complex with mutant beta subunits were about 20 and 30% of those with the wild-type subunit. The rate of ATP binding (k1) of the mutant complex under uni-site conditions was about 10-fold less than that of the wild type complex. These results suggest that Thr-285, or the region in its vicinity, is essential for normal catalysis of the H+-ATPase. The mutant complex could not form a phosphoenzyme under the conditions where the H+/K+-ATPase is phosphorylated, suggesting that another residue(s) may also be involved in formation of the intermediate in ion motive ATPase. The wild-type alpha beta gamma complex had slightly different kinetic properties from the wild-type F1, possibly because it did not contain the epsilon subunit. PMID- 2897963 TI - Topography and subunit stoichiometry of the coated vesicle proton pump. AB - We have previously shown that the coated vesicle (H+)-ATPase contains nine polypeptides of molecular weight 17,000-100,000 which form a single, macromolecular complex that can be immunoprecipitated using monoclonal antibodies which recognize the native enzyme (Arai, H., Berne, M., Terres, G., Terres, H., Puopolo, K., and Forgac, M. (1987) Biochemistry 26, 6632-6638). In the present paper, we have calculated from quantitative amino acid analysis that these polypeptides are present in the native complex in a stoichiometry of three copies each of the 73,000- and 58,000-dalton subunits, six copies of the 17,000-dalton subunit, and one copy each of the 100,000-, 40,000-, 38,000-, 34,000-, 33,000-, and 19,000-dalton subunits. To determine the disposition of the (H+)-ATPase subunits with respect to the membrane, we have carried out labeling studies using the membrane impermeant reagents Na125I/lactoperoxidase and 125I-sulfo succinimidyl-3-(4-hydroxyphenyl)propionate and the hydrophobic reagent 3 (trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine [( 125I]TID). Polypeptides exposed to the cytoplasmic surface were identified by labeling with impermeant reagents in intact vesicles from which clathrin had been dissociated followed by immunoprecipitation of the native enzyme. Polypeptides exposed to the luminal surface were identified by increased labeling by these reagents following detergent solubilization under nondenaturing conditions. Labeling by [125I]TID was used to indicate which polypeptides are embedded in the lipid bilayer. Results of these experiments indicate that the principal polypeptides labeled from the cytoplasmic surface are those of molecular weight 73,000 and 58,000, although some cytoplasmic labeling of the 100,000, 40,000, 38,000 and 34,000/33,000 polypeptides was also observed. The polypeptides which show the greatest increase in labeling following detergent solubilization are those of molecular weight 100,000, 19,000, and 17,000, with some increase observed for the 40,000, 38,000, and 34,000/33,000 polypeptides. [125I]TID labeled the 17,000 dalton subunit most heavily, with significant labeling of the 100,000- and 40,000 dalton subunits also observed. In addition, we find that the 73,000-dalton polypeptide can be dissociated from the complex with 0.5 M KI in the absence of detergent, indicating a peripheral association of this subunit with the membrane. We have combined these results to construct a structural model of the coated vesicle (H+)-ATPase. PMID- 2897964 TI - Acetyl-coenzyme A:polysialic acid O-acetyltransferase from K1-positive Escherichia coli. The enzyme responsible for the O-acetyl plus phenotype and for O-acetyl form variation. AB - The capsular polysaccharide of Escherichia coli K1 is a linear polymer of N acetylneuraminic acid in alpha-2,8 linkage. Certain substrains of E. coli K1 (designated OAc+) modify the polysaccharide by O-acetylation of the sialic acids. We demonstrate here an acetyl-coenzyme A: polysialosyl O-acetyltransferase activity that is found only in E. coli K1 OAc+ substrains. When form variation between the O-acetyl-positive and -negative states occurred in strain D698:K1, the fluctuations were accompanied by appropriate changes in the expression of enzyme activity. Thus, expression of this enzyme can account for the OAc+ phenotype and for the form variation between OAc+ and OAc-. The enzyme was solubilized in nonionic detergent and freed of endogenous acceptor activity by DEAE-cellulose chromatography, and its general properties were determined. Analysis of the reaction product showed a highly preferential acetylation reaction that was confined to polysialosyl units of greater than 14 residues. Acetyl groups were shown to be transferred to both the 7- and the 9-positions of the sialic acid residues. The partially purified enzyme was stable even after prolonged incubation at 57 degrees C. In contrast, any further purification resulted in loss of activity, even at 4 degrees C. Treatment of the stable enzyme with a polysialic acid-specific endoneuraminidase caused a similar loss of enzyme stability. This effect of the endoneuraminidase could be protected against by the addition of exogenous polysialic acid. This indicates that the partially purified enzyme contains traces of endogenous polysialic acid substrate that are required for the stability of the enzyme. Finally, the enzyme can O-acetylate the polysialic acid chains on the eucaryotic protein neural cell adhesion molecule, suggesting that enzymatic recognition of the substrate requires only the polysialic acid sequence. PMID- 2897965 TI - The cDNA sequence of the 69-kDa subunit of the carrot vacuolar H+-ATPase. Homology to the beta-chain of F0F1-ATPases. AB - Vacuolar ATPases constitute a novel class of N-ethylmaleimide- and nitrate sensitive proton pumps associated with the endomembrane system of eukaryotic cells. They resemble F0F1-ATPases in that they are large multimeric proteins, 400 500 kDa, composed of three to nine different subunits. Previous studies have indicated that the active site is located on the approximately 70-kDa subunit. Using antibodies to the approximately 70-kDa subunit of corn to screen a carrot root lambda gt11 cDNA library, we have isolated cDNA clones of the carrot 69-kDa subunit. The complete primary structure of the 69-kDa subunit was then determined from the nucleotide sequence of its cDNA. The 69-kDa subunit consists of 623 amino acids (Mr 68,835), with no obvious membrane-spanning regions. The carrot cDNA sequence was over 70% homologous with exons of a Neurospora 69-kDa genomic clone. The protein sequence of the carrot 69-kDa subunit also exhibited 34.3% identity to four representative F0F1-ATPase beta-chains over a 275-amino-acid core stretch of similar sequence. Alignment studies revealed several regions which were highly homologous to beta-chains, including sequences previously implicated in catalytic function. This provides definitive evidence that the vacuolar ATPase is closely related to the F0F1-type ATPases. A major functional difference between the 69-kDa and beta-subunits is the location of 3 critical cysteine residues: two in the putative catalytic region (Cys-248 and Cys-256) and one in the proposed Mg2+-binding site (Cys-279). These cysteines (and two others) probably account for the sensitivity of the vacuolar H+-ATPase to the sulfhydryl reagent, N-ethylmaleimide. It is proposed that the two ATPases may have arisen from a common ancestor by the insertion or deletion of a large stretch of nonhomologous sequence near the amino-terminal end of the subunit. PMID- 2897966 TI - Protein kinase C: subcellular redistribution by increased Ca2+ influx. Evidence that Ca2+-dependent subcellular redistribution of protein kinase C is involved in potentiation of beta-adrenergic stimulation of pineal cAMP and cGMP by K+ and A23187. AB - Phenylephrine is known to stimulate translocation of protein kinase C in rat pinealocytes (Sugden, D., Vanecek, J., Klein, D.C., Thomas, T.P., and Anderson, W. B. (1985) Nature 314, 359-361). In the present study, the receptor mediating this effect was found to belong to the alpha 1-adrenoceptor subclass. Activation of this receptor is also known to produce a sustained increase in [Ca2+]i by increasing net influx (Sugden, A. L., Sugden, D., and Klein, D. C. (1985) J. Biol. Chem. 261, 11608-11612), which points to the possible importance of Ca2+ influx in the subcellular redistribution (activation) of protein kinase C in intact cells. This possibility was investigated by reducing extracellular Ca2+ ((Ca2+]o) with EGTA or by inhibiting Ca2+ influx with inorganic Ca2+ blockers. These treatments reduced alpha 1-adrenoceptor-mediated translocation of protein kinase C. This suggested that elevation of Ca2+ influx alone triggers activation of protein kinase C. In support of this, it was found that treatments which elevate Ca2+ influx, including increased extracellular K+ and addition of the Ca2+ ionophore A23187, cause redistribution of protein kinase C. The effect of K+ was blocked by nifedipine and that of A23187 by EGTA, indicating that effects of these agents are Ca2+-dependent. The possible role of phospholipase C activation in these effects was examined by measuring the formation of [3H]diacylglycerol by cells labeled with [3H]arachidonic acid. Although [3H]diacylglycerol formation was easily detected in the presence or absence of an effective concentration of an inhibitor of diacylglycerol kinase, none of the agents which cause rapid translocation of protein kinase C were found to cause a rapid increase in the generation of [3H]diacylglycerol. These findings establish that an increase in Ca2+ influx is sufficient to trigger translocation of protein kinase C. In addition, we found that a very close correlation exists between translocation of protein kinase C by phenylephrine, K+, and A23187 and their ability to potentiate beta-adrenergic stimulation of cAMP and cGMP accumulation. This provides strong support to the proposal that translocation of protein kinase C is required for potentiation of beta-adrenergic stimulation of pinealocyte cAMP and cGMP accumulation. PMID- 2897967 TI - The multifunctional Ca2+/calmodulin-dependent protein kinase mediates Ca2+ dependent phosphorylation of tyrosine hydroxylase. AB - Stimulation of rat pheochromocytoma PC12 cells with ionophore A23187, carbachol, or high K+ medium, agents which increase intracellular Ca2+, results in the phosphorylation and activation of tyrosine hydroxylase (Nose, P., Griffith, L. C., and Schulman, H. (1985) J. Cell Biol. 101, 1182-1190). We have identified three major protein kinases in PC12 cells and investigated their roles in the Ca2+-dependent phosphorylation of tyrosine hydroxylase and other cytosolic proteins. A set of PC12 proteins were phosphorylated in response to both elevation of intracellular Ca2+ and to protein kinase C (Ca2+/phospholipid dependent protein kinase) activators. In addition, distinct sets of proteins responded to either one or the other stimulus. The three major regulatory kinases, the multifunctional Ca2+/calmodulin-dependent protein kinase, the cAMP dependent protein kinase, and protein kinase C all phosphorylate tyrosine hydroxylase in vitro. Neither the agents which increase Ca2+ nor the agents which directly activate kinase C (12-O-tetradecanoylphorbol-13-acetate or 1-oleyl-2 acetylglycerol) increase cAMP or activate the cAMP-dependent protein kinase, thereby excluding this pathway as a mediator of these stimuli. The role of protein kinase C was assessed by long term treatment of PC12 cells with 12-O tetradecanoylphorbol-13-acetate, which causes its "desensitization." In cells pretreated in this manner, agents which increase Ca2+ influx continue to stimulate tyrosine hydroxylase phosphorylation maximally, while protein kinase C activators are completely ineffective. Comparison of tryptic peptide maps of tyrosine hydroxylase phosphorylated by the three protein kinases in vitro with phosphopeptide maps generated from tyrosine hydroxylase phosphorylated in vivo indicates that phosphorylation by the Ca2+/calmodulin-dependent kinase most closely mirrors the in vivo phosphorylation pattern. These results indicate that the multifunctional Ca2+/calmodulin-dependent protein kinase mediates phosphorylation of tyrosine hydroxylase by hormonal and electrical stimuli which elevate intracellular Ca2+ in PC12 cells. PMID- 2897969 TI - Calmodulin plays a dominant role in determining neurotransmitter regulation of neuronal adenylate cyclase. AB - Ca2+, through the mediation of calmodulin, stimulates the activity of brain adenylate cyclase. The growing awareness that fluctuating Ca2+ concentrations play a major role in intracellular signalling prompted the present study, which aimed to investigate the implications for neurotransmitter (receptor) regulation of enzymatic activity of this calmodulin regulation. The role of Ca2+/calmodulin in regulating neurotransmitter-mediated inhibition and stimulation was assessed in a number of rat brain areas. Ca2+/calmodulin stimulated adenylate cyclase activity in EGTA-washed plasma preparations from each region studied--from 1.3 fold (in striatum) to 3.4-fold (in cerebral cortex). The fold-stimulation produced by Ca2+/calmodulin was decreased in the presence of GTP, forskolin, or Mn2+. In EGTA-washed membranes, receptor-mediated inhibition of adenylate cyclase was strictly dependent upon Ca2+/calmodulin stimulation in all regions, except striatum. A requirement for Mg2+ in combination with Ca2+/calmodulin to observe neurotransmitter-mediated inhibition was also observed. In contrast, receptor mediated stimulation of activity was much greater in the absence of Ca2+/calmodulin. The findings demonstrate that ambient Ca2+ concentrations, in concert with endogenous calmodulin, may play a central role in dictating whether inhibition or stimulation of adenylate cyclase by neurotransmitters may proceed. PMID- 2897970 TI - Genetic counseling: using the information wisely. PMID- 2897968 TI - Assessment of biological activity of synthetic fragments of transforming growth factor-alpha. AB - Transforming growth factor-alpha (TGF-alpha) is a single chain polypeptide hormone of 50 amino acids that stimulates growth of some human cancer cells via an autocrine mechanism. The domain(s) of TGF-alpha that bind and activate its receptor have not been reported. Hydrophilicity plots of TGF-alpha indicate three discrete sequences that are theoretically exposed on the hormone's surface and thus potentially able to interact with the TGF-alpha receptor. Fragments of TGF alpha encompassing these hydrophilic domains were prepared by using solid-phase peptide synthesis (SPPS) techniques and purified by use of high performance liquid chromotography (HPLC). Assessment of biological activity of the TGF-alpha fragments indicated that none of the fragments significantly inhibited binding of EGF to the receptor, stimulated DNA synthesis of cells, inhibited EGF-induced DNA synthesis of cells, stimulated growth of cells in soft agar, or induced phosphorylation of the receptor or p35 protein. These results indicate that the receptor binding domain of TGF-alpha is not totally encompassed by any of the separate fragments tested and probably is formed by multiple separate regions of TGF-alpha. PMID- 2897971 TI - Neurosurgery for the pain of malignancy. PMID- 2897972 TI - Mitogenic activity on parathyroid cells in plasma from members of a large kindred with multiple endocrine neoplasia type 1. AB - We tested plasma from 83 members of a large kindred with familial multiple endocrine neoplasia type 1 (FMEN1) for mitogenic activity on cultured bovine parathyroid cells. We evaluated the age dependency of parathyroid mitogenic activity (PMA) in plasma from affected and unaffected members of the kindred, and we analyzed the relation of plasma PMA to indices of activity of parathyroid, pancreatic islet, and anterior pituitary tissue. Plasma PMA was higher in members expressing the FMEN1 gene than in their unaffected first, second, third, or fourth degree relatives (P less than 0.05), and 10 of 20 members expressing the FMEN1 gene had plasma PMA above the 95% limit of the control range. Plasma PMA was not dependent on sex or age; the lack of age dependency and the high values in FMEN1 gene carriers suggested that plasma PMA is elevated in some FMEN1 gene carriers very early in life. Plasma PMA in known gene carriers varied significantly with one index of parathyroid function [plasma PMA was 2.5 times higher in the group with than in the group without prior parathyroidectomy (P less than 0.005), an indicator of more severe prior parathyroid disease] and correlated positively, although not significantly so, with indices of pancreatic islet function (serum gastrin by RIA) and anterior pituitary function (serum PRL by RIA). In summary, (1) plasma PMA levels are high in many known carriers of the FMEN1 gene, (2) the high plasma PMA levels in FMEN1 may precede overt endocrine hyperfunction; and (3) high plasma PMA levels vary with one index of parathyroid function, but do not correlate with indices of pancreatic islet or anterior pituitary function in members expressing the FMEN1 gene. The high plasma PMA levels in FMEN1 may be the direct cause of hyperfunction of the parathyroids, but the relation of high plasma PMA to hyperfunction of the pancreatic islets and anterior pituitary is uncertain. PMID- 2897974 TI - Plasma insulin-like growth factor-I/somatomedin-C in acromegaly: correlation with the degree of growth hormone hypersecretion. AB - We measured plasma insulin-like growth factor I/somatomedin-C (IGF-I/SmC) concentrations and mean 24-h GH secretion serially before and during therapy with the long-acting somatostatin analog SMS 201-995 in 21 patients with acromegaly. When mean plasma GH was elevated above 12.0 +/- 0.6 (+/- SE) micrograms/L, plasma IGF-I/SmC concentrations were uniformly high, but a decline of mean plasma GH below this value was accompanied by a linear decrease in IGF-I/SmC concentrations (r = 0.89; P less than 0.001). Even mildly abnormal mean GH concentrations (greater than 4.6 but less than 10 micrograms/L) were accompanied by high plasma IGF-I/SmC values. The log dose-response interrelation between mean 24-h plasma GH and IGF-I/SmC concentrations was linear (r = 0.86; P less than 0.001). We conclude that 1) an excellent log dose-response correlation between mean 24-h plasma GH and IGF-I/SmC concentrations is present in patients with acromegaly; 2) normalization of plasma IGF-I/SmC occurs only in patients with mean daily GH output within the normal range; and 3) determination of plasma IGF-I/SmC is an accurate indicator of normalcy of GH secretion and should be used in the diagnosis of active acromegaly as well as in monitoring the progress of therapy. PMID- 2897973 TI - Somatostatin-secreting islet cell tumor (somatostatinoma): suppression of growth hormone (GH) release induced by GH-releasing hormone. AB - A patient with a somatostatin (SRIH)-secreting islet cell tumor, whose only symptoms were dyspepsia and anemia, is described. The diagnosis of somatostatinoma was based on high plasma SRIH concentrations and immunocytochemical findings. The pancreatic exocrine response to secretin was decreased, whereas the insulin and/or glucagon responses to glucose and arginine were normal. Although the basal plasma GH concentration was normal, the plasma GH response to GHRH was subnormal. Gel permeation chromatography studies indicated that SRIH-14 was the predominant form of SRIH in plasma as well as in tumor tissue. PMID- 2897975 TI - Early pregnancy and benzodiazepines. PMID- 2897976 TI - Risks and benefits of long-term benzodiazepine use. AB - Despite a sharp decline in the prescription of benzodiazepines during the past decade, reservations about their use have continued to escalate. This article presents converging data from three diverse sources: national survey data from consumers, laboratory data on the drug preferences of normal subjects, and a controlled clinical study of long-term diazepam treatment and withdrawal. These data suggest that (1) the risks of overuse, dependence, and addiction with benzodiazepines are low in relation to the massive exposure in our society; (2) benzodiazepine addiction can occur when doses within the clinical range are taken regularly over about 6 months; (3) many patients continue to derive benefit from long-term treatment with benzodiazepines; and (4) attitudes strongly against the use of these drugs may be depriving many anxious patients of appropriate treatment. PMID- 2897977 TI - Survey method for post-marketing drug surveillance: a demonstration. AB - Distinguishing characteristics of a community survey method for post-marketing drug monitoring are described, as are results of a pilot study of the method. Representative samples of outpatients treated with tricyclic antidepressants or benzodiazepine anxiolytics were identified in a clinic or pharmacy and interviewed at baseline and specified intervals thereafter in the home or by telephone. Data were collected by lay interviewers trained to use a detailed interview schedule designed with input from experts in pharmacology, relevant clinical disciplines, and survey research. The critical validity question was the degree to which predicted outcomes for the two well-studied drug classes matched observed outcomes. The analytic design involved two contrast groups, three measurement periods, and six key symptom measures. The latter were specific to the disorder (anxiety and depression), to the medications, or to neither the disorders nor the medication (neutral symptoms). Predictions took account of degree and direction of change, as well as differences in profile levels over time. Results conformed precisely to expectations. As one component of a comprehensive system, the method provides an opportunity to examine efficacy as well as safety under conditions that are typically absent or excluded in clinical trials. Data on patterns of prescribing by physicians and use by patients are valuable by-products that are immediately relevant for professional education and product liability. Advantages and limitations of the method are discussed. PMID- 2897978 TI - Comparative neurologic effects of diazepam and suriclone, a cyclopyrrolone anxiolytic. AB - Suriclone selectively displaces benzodiazepines from their binding sites but is structurally unrelated to benzodiazepines. Neurologic effects of suriclone were compared to those of diazepam in 54 subjects in a sequential, double-blind, single dose, randomized study (placebo; diazepam 10 mg; suriclone 0.2, 0.4, 0.6, or 0.8 mg). Data were collected on-line by microcomputer. Suriclone 0.2 mg did not differ from placebo. Suriclone 0.4 mg and 0.6 mg did not differ from diazepam 10 mg. Suriclone 0.8 mg caused significantly more decrement than diazepam 10 mg (p less than 0.05) in manual tracking, force platform stability, and Heath rail walking and in total severity of symptoms. Suriclone 0.8 mg caused nausea (p = 0.02), clumsiness (p = 0.02), and loss of balance (p = 0.01) more frequently than diazepam 10 mg. Suriclone 0.8 mg produced symptoms and signs qualitatively and quantitatively different from diazepam 10 mg, such as vomiting, unusual ocular movement effects, and difficulty walking. Possibly the differences in CNS drug binding for anxiolytics are associated with clinical differences in toxicity. PMID- 2897979 TI - Affective and cognitive problems with the benzodiazepines. PMID- 2897980 TI - The Pisa syndrome: possible role for serotonin and noradrenaline. PMID- 2897981 TI - Immunocytochemical localization of peptides and other neurochemicals in the rat laterodorsal tegmental nucleus and adjacent area. AB - The laterodorsal tegmental nucleus (ntdl) contains a cluster of cells located just medial to the locus coeruleus in the pontine brainstem. The ntdl has been shown to project both rostrally to the forebrain and diencephalon and caudally to the spinal cord. In an effort to characterize this region neurochemically, the present study was conducted to identify a variety of neurochemicals localized within perikarya and fibers of the ntdl and surrounding nuclei. Rats were perfused with formalin, and brain sections were processed for fluorescence immunocytochemistry and acetylcholinesterase (AChE). Of the neurochemicals screened, atrial natriuretic factor (ANF), choline acetyltransferase (ChAT), cholecystokinin (CCK), calcitonin gene-related peptide (CGRP), dynorphin B (Dyn B), galanin, somatostatin, substance P, neurotensin (NT), neuropeptide Y (NPY), vasopressin, vasoactive intestinal polypeptide (VIP), serotonin (5HT), glutamic acid decarboxylase (GAD), and tyrosine hydroxylase (TH) were studied. AChE and ChAT staining revealed that the ntdl contains mostly cholinergic neurons. In addition, brightly reactive substance P and galanin and paler staining CRF, ANF, CGRP, NT, VIP, and Dyn B cell bodies were found within the ntdl. Varicose fibers in this nucleus also contained these peptides in addition to CCK, GAD, TH, 5HT, and NPY. The dorsal tegmental nucleus, dorsal raphe nucleus, locus coeruleus, and the parabrachial region contained a dense and varied assortment of peptides with distinct positions and patterns. This multiplicity of neurochemicals within this area suggests a possible influence on a variety of functions modulated by the ntdl and other closely associated tegmental nuclei. PMID- 2897982 TI - Somatostatin-containing neuron systems in the rat hypothalamus: retrograde tracing and immunohistochemical studies. AB - By employing a combination of the immunohistochemistry for somatostatin (SRIF) and retrograde tracing with biotinylated wheat germ agglutinin (b-WGA) injected into the posterior pituitary (group 1) or into the median eminence (group 2), functional topography of hypothalamic SRIF neurons was determined in the rat hypothalamus. In group 1, large numbers of WGA-labeled neurons appeared in the rostral periventricular region and in the magnocellular division of the paraventricular and supraoptic nuclei; none of them were SRIF immunoreactive. In group 2, WGA-labeled neurons were numerous in the rostral periventricular region, the parvicellular division of the paraventricular nucleus, and the arcuate nucleus; most of the WGA-labeled neurons in the rostral periventricular region and some in the paraventricular nucleus were SRIF immunoreactive, but none in the arcuate nucleus showed immunoreactivity for SRIF. It is concluded that, in the rat hypothalamus, the locations of neurons containing hypophysiotrophic SRIF are confined within the rostral periventricular region and the parvicellular paraventricular nucleus. Our results do not support previous suggestions that SRIF immunoreactive axons innervate the posterior lobe of the pituitary. PMID- 2897983 TI - Report on the European Conference on Septic Shock of the European Society of Intensive Care Medicine and the European Shock Society, Brussels, Belgium, March 1-2, 1987. PMID- 2897984 TI - Masticatory muscle hyperactivity in temporomandibular disorders: is it an extrapyramidally expressed disorder? AB - Masticatory muscle hyperactivity appears to have an important role in temporomandibular disorders. A pathophysiological model for masticatory muscle hyperactivity is proposed that is centrally mediated, yet maintains support for present peripheral causes and therapies. In this hypothesis, masticatory muscle hyperactivity represents a mild extrapyramidal disorder distantly related to orofacial dyskinesias. Experimental evidence suggests a neurotransmitter imbalance in the basal ganglia, involving dopaminergic preponderance, or cholinergic and GABA-nergic hypofunction as the underlying cause. PMID- 2897985 TI - Success of internal mammary bypass grafting can be assessed intraoperatively using myocardial contrast echocardiography. AB - To determine whether the success of internal mammary artery bypass grafting can be assessed intraoperatively using myocardial contrast echocardiography, sonicated Renografin-76 was injected into the aortic root of 11 dogs during the delivery of cardioplegic solution. Studies were performed with the left anterior descending coronary artery patent and totally occluded, and after internal mammary artery bypass grafting distal to the occluded vessel. Flow rate during cardioplegia was constant for all three stages in each experiment. Myocardial contrast echocardiography clearly demonstrated homogeneous myocardial perfusion with the left anterior descending coronary artery patent, lack of perfusion in the left anterior descending artery bed during its occlusion and excellent perfusion of the occluded bed after internal mammary artery bypass grafting distal to the occlusion in 10 of the 11 dogs. In one dog, the bypass graft was technically inadequate and contrast opacification was not noted in the left anterior descending artery bed after internal mammary artery bypass grafting. The exponential function C(t) = Ae-alpha t + Be-beta t was fitted to computer-derived time-intensity curves from the myocardium, where alpha denotes contrast washout and beta denotes contrast appearance. Respective values for alpha and beta (mean + 1 SD) were similar for the patent left anterior descending coronary artery and after internal mammary artery bypass grafting distal to the occluded artery (0.11 +/- 0.10 versus 0.10 +/- 0.10, and 2.5 +/- 2.4 versus 1.1 +/- 0.56). In conclusion, myocardial contrast echocardiography has potential for intraoperative assessment of the adequacy of coronary artery bypass grafting. PMID- 2897987 TI - Effect of theophylline on gastroesophageal reflux in patients with asthma. AB - A possible role of methylxanthines in the high incidence of gastroesophageal reflux (GER) in patients with asthma has been suggested. Therefore, we used a randomized, double-blind, crossover design to compare the effects of a 1-week conventional theophylline treatment and a 1-week placebo treatment in 16 adult patients with asthma. No oral or parenteral glucocorticoids were administered, but seven patients were taking inhaled corticoids. All patients needed inhaled adrenergic drugs. At the end of each period of theophylline or placebo treatment, the patients were carefully questioned with respect to respiratory and digestive symptoms, forced expiratory flows were measured, and GER was assessed by prolonged nocturnal intraesophageal pH monitoring. Peak expiratory flow was measured three times a day throughout the study. No significant increase in GER was found with theophylline compared to placebo, and forced expiratory flows improved with theophylline (p less than 0.05 for FEV1 and p less than 0.01 for peak expiratory flow rate). There was no correlation between GER, the duration of asthma, and forced expiratory flows. Thus, our study failed to demonstrate any adverse effect of a slow-release theophylline preparation on GER in patients with asthma. These results further suggest that the presence of GER is not a contraindication to the use of a slow-release theophylline in subjects with asthma. PMID- 2897986 TI - Hay fever treatment with combined antihistamine and cyclooxygenase-inhibiting drugs. AB - Twenty-eight ragweed-allergic patients with hay fever participated in a clinical trial that examined the pattern of symptom relief resulting from addition of a cyclooxygenase-inhibiting drug to standard antihistamine therapy. In the first week antihistamine use by the subjects was standardized, and subjects were oriented to use of the hay fever symptom diary. They were then allocated, according to symptom severity, to two treatment groups. One group received 120 mg of terfenadine and 300 mg of flurbiprofen (a cyclooxygenase-inhibiting drug) per day. Members of the other group received terfenadine and a placebo that looked like flurbiprofen. This treatment lasted 1 week. Subjects recorded severity of congestion, drainage, running, nose blowing, itching, and sneezing four times each day. The flurbiprofen-treated patients experienced less severe symptoms, demonstrating maximum benefit 3 to 5 days into the drug trial with some loss of effect thereafter. Secretion-related symptoms appeared to benefit most. Combined blockade of histamine and cyclooxygenase products appears to offer improved symptom control in ragweed hay fever. PMID- 2897988 TI - Platelet aggregation in hypertension and the effects of antihypertensive treatment. AB - The major findings of a review of the literature on platelet aggregation in hypertensive human subjects and the effects of antihypertensive agents were as follows: (1) There is an increased platelet aggregatory response to epinephrine and ADP in hypertensives with MAP greater than 120 mmHg. (2) Treatment with propranolol decreases the aggregatory response to ADP, but it may enhance the response to epinephrine. (3) Treatment with calcium blockers in normotensives decreases the aggregatory response to epinephrine. Further work needs to be done to answer the questions raised by this review. Since the major goal, yet unachieved, of antihypertensive therapy is reduction of the incidence of CHD, the anti-thrombotic or thrombotic potential of antihypertensive agents must be known. Future clinical trials of drug therapy for hypertension should be designed to include at least a determination of platelet aggregation in response to both ADP and epinephrine. PMID- 2897989 TI - Desensitization of vascular and platelet alpha 2-adrenoceptors in rabbits with perinephritis hypertension. AB - The effects of infusion of alpha-adrenoceptor agonists on blood pressure, pressor responses to bolus doses of agonists and to platelet aggregation were examined in rabbits with perinephritis hypertension and in sham-operated controls. Pressor responses to bolus doses and infusions of phenylephrine, an alpha 1-selective agonist, were greater in hypertensive rabbits. In contrast, responses to boluses but not infusions of alpha-methylnoradrenaline, a selective alpha 2-agonist, were increased in hypertensives. During alpha-methylnoradrenaline infusions pressor responses to bolus doses of alpha-methylnoradrenaline and the aggregatory response of platelets to adrenaline were attenuated in all rabbits, consistent with alpha 2-adrenoceptor desensitization. Attenuation and recovery were observed within minutes of commencing and ceasing infusion. The extent of attenuation and rate of change were generally increased in hypertensive animals. This could explain the apparent increase in pressor responses to bolus doses but not infusions of alpha-methylnoradrenaline in the hypertensive rabbits. It might also contribute to the lability in blood pressure observed in these animals. PMID- 2897990 TI - The cardiovascular responses to sequential inhibition of alpha-adrenoceptors, the renin-angiotensin system and vasopressin in rats with adrenal regeneration hypertension. AB - The cardiovascular responses to selective alpha 1- and alpha 2-adrenoceptor antagonism (with prazosin and idazoxan, respectively) were assessed in rats 4 weeks after unilateral nephro-adrenalectomy, contralateral adrenal enucleation and the provision of a 1% NaCl solution as drinking fluid (AEN rats) and in sham operated (SON) rats. Measurements were made between 0700 and 1000 h and between 1400 and 1700 h, since we have previously shown that resting blood pressures (BPs) in AEN rats are higher in the morning than in the afternoon. Following prazosin administration (morning or afternoon), BP fell to similar levels in both SON and AEN rats. Idazoxan, given 20 min after the start of prazosin infusion, caused similar transient falls in BP in all four groups of rats. Following the subsequent additional antagonism of angiotensin II (Ang II) production (with captopril) and vasopressin (V1) receptors [with d(CH2)5DAVP], BP in AEN rats studied in the morning was higher than in SON rats at that time of day, and higher than in AEN rats studied in the afternoon. These findings suggest than an additional underlying mechanism capable of increasing BP exists in AEN rats studied in the morning. PMID- 2897991 TI - Identification of suppressor T cells in virgin non-responder spleen cells responsible for primary unresponsiveness to L-glutamic acid60-L-alanine30-L tyrosine10 (GAT). AB - T cell subsets that regulate antibody responses to L-glutamic acid60-L-alanine30 L-tyrosine10 (GAT) in mice that are Ir gene non-responders have been further characterized. We previously defined several T cell subsets in GAT-primed non responder mice. The Lyt-2+ suppressor-effector T cells suppress responses to GAT and GAT complexed to methylated BSA (GAT-MBSA). The Lyt-1+ cell population is complex and can be separated into I-J- Th cells, which support responses to GAT and GAT-MBSA. After priming, the Lyt-1+, I-J+ cell population contains suppressor inducer cells that activate precursors of suppressor-effector cells to suppress responses to GAT and GAT-MBSA as well as Ts cells that directly inhibit responses to GAT but not GAT-MBSA. By contrast, the Lyt-1+ cells from virgin mice contain only cells that directly suppress responses to GAT but not GAT-MBSA. The major question addressed in the present studies was whether the Lyt-1+, I-J+ Ts cells in virgin and primed mice and the suppressor-inducer cells in GAT-primed mice were functionally and serologically distinct subsets. The studies used mAb and panning procedures to separate cell populations and inhibition of PFC cell responses to functionally define the activity of the cell populations. We used the following two mAb that were raised by immunizing rats with GAT-specific suppressor factors: 1248A4.10 (known to react with suppressor-inducer cells) and 1248A4.3, another reagent from the same fusion. Lyt-1+ cells from virgin spleens contained Ts cells that were A4.10-, A4.3+ and no suppressor-inducer T cells, whereas Lyt-1+ cells from GAT-primed spleens contained Ts cells that were A4.10-, A4.3+ as well as A4.10+, A4.3- suppressor-inducer cells. Thus, the Lyt1+, I-J+ cell subset can be divided into two functionally and serologically distinct subsets, direct Ts cells (1248A4.3+), which suppress responses to GAT but not GAT MBSA, and GAT-primed suppressor-inducer T cells (1248A4.10+). PMID- 2897992 TI - Neuroimmunological electron microscopy with microwave-accelerated fixation. AB - Immunoelectron microscopy is an important tool used to determine the precise location of immune complexes. Standard concentrations of glutaraldehyde destroy these complexes. This paper describes a method in which the period of glutaraldehyde fixation is shortened by concomitant microwave treatment. Using 1.25% glutaraldehyde and microwave fixation ideal preservation and demonstration of MHC class I antigen on Schwann cells was obtained by the peroxidase method. PMID- 2897993 TI - Malignant melanoma over the trophic ulcer. AB - One case having trophic ulcer over the heel which on histological examination showed malignant melanoma is reported because of malignant melanoma occurring over the trophic ulcer. PMID- 2897994 TI - In vitro cytotoxic activity of interleukin 2-dependent murine Thy-1+ dendritic epidermal cell lines. AB - Thy-1+ dendritic epidermal cells (Tdec) are bone marrow-derived cells of T-cell lineage. In order to investigate the function of these cells, two interleukin 2 dependent Tdec lines (AU4 and AU16) were established from ear skin of C3H/HeN (MTV-) mice and examined for cytotoxicity against various murine tumor cells. The original phenotype of the Tdec, Thy-1+, AsGM1+, T3+, Lyt-1-, Lyt-2-, Lyt-5+, and L3T4-, was maintained in the cell lines. The Tdec cell lines (AU4 and AU16) lysed a wide spectrum of tumor cell lines in a 4-hr 51Cr-release assay. AU16 was more effective in killing a syngeneic UV-induced skin tumor (UV-2240) and an allogeneic, natural killer cell-resistant tumor (EL-4) than the YAC-1 cell line, which is highly sensitive to natural killer cells. Neither syngeneic nor allogeneic lymphoblasts were killed by AU16. Cytotoxicity was blocked by fixation of AU16 with paraformaldehyde but not by pretreatment of the cells with puromycin or mitomycin C. The finding that two Thy-1+ cell lines derived independently from murine epidermis have unique cytotoxic activity against murine tumor cells suggests that Tdec could play a role in local immune surveillance against skin cancers. PMID- 2897995 TI - Withdrawal of endogenous somatostatin induces secretion of growth hormone releasing factor in rats. AB - Secretion of GH occurs in episodic bursts under the dual control of two hypothalamic peptides, GH-releasing factor (GRF) and GH-inhibiting factor (somatostatin, SRIF). Recent studies in rats suggest that episodic GH secretion is generated by the periodic release of GRF, which is associated with the simultaneous withdrawal of SRIF secretion. To test the possibility that GRF discharge is functionally coupled with the withdrawal of SRIF, we investigated whether acute withdrawal of SRIF can induce GRF release by the rat hypothalamus using highly specific antisera against SRIF and rat GRF. In conscious unrestrained rats, i.v. administration of SRIF antiserum at the period of the GH trough induced a rapid onset of the GH secretory surge with a peak value of 309 +/- 67 micrograms/l (mean +/- S.E.M.) 30 min after injection. Pretreatment with antiserum to rat GRF resulted in a approximately 83% suppression of the GH surge induced by SRIF antiserum without affecting the trough GH values. GRF antiserum also significantly inhibited the spontaneous GH surge. In urethane-anaesthetized rats, as in conscious rats, an acute phasic GH release was caused by SRIF antiserum despite the interference of anaesthesia with spontaneous GH secretion. A further surge-like GH secretion was not restored during the next several hours, however, with the GH secretory profile being characterized by a tonic increase in the baseline levels of GH. In the anaesthetized rat antiserum to rat GRF, having no effect on basal GH levels, similarly inhibited by approximately 66% the acute GH surge induced by SRIF antiserum and decreased by about 30% the later sustained rise in GH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897997 TI - [Polymorphism of restriction fragment length in the detection of the precise status of monosomy 21 in a deformed retarded girl]. AB - The authors used genomic single copy DNA fragments cloned from chromosome 21 to study cytogenetic abnormalities in patients not easily defined by conventional cytogenetic means. Ten restriction fragment length polymorphisms (RLFP) detected by 8 independent probes were used to detect homologous sequences from chromosome 21 in genomic digests of DNA from one patient and her parents. The proband is a 3 1/2-year-old girl who was referred to us at 1 month of age because of hypertonia, hirsutism, flattened nasal bridge, antimongoloid slant of palpebral fissures, high arched palate and bilateral hip dysplasia. The karyotype of the proband was: 46, XX, -3, -21, + ? del (3) (3 pter----3q1:) +? (3qter----3q1:: 21q21----21 pter). GTG banding and the karyotype of her parents were normal (in peripheral blood and skin fibroblasts). She was re-examined by us every three months, because she showed physical and psychomotor retardation. We traced the inheritance of RFLPs from her parents, and familial molecular studies showed in contrast to the cytogenetic analysis that the patient is disomic for all regions of 21q tested by our collection of probes. The use of molecular technology has resulted in a more precise definition of 21 chromosome abnormalities and especially the "complete" monosomy 21 which is extremely rare in live born infants. PMID- 2897996 TI - Involvement of the somatostatin and cholinergic systems in the mechanism of growth hormone autofeedback regulation in the rat. AB - The involvement of the cholinergic system in GH secretion has recently acquired increasing importance. Data have been presented suggesting that in rats the effect of cholinergic modulation on GH secretion takes place through inhibition or stimulation of hypothalamic somatostatin (SRIF) release. To investigate further the significance of cholinergic-SRIF link and its role in the regulation of GH secretion, the action of cholinergic agonist and antagonist drugs in the GH short-loop feedback mechanism mediated by SRIF was investigated. Intracerebroventricular (i.c.v.) infusion of 0.2 or 2.0 micrograms GH/rat into the lateral brain ventricle of adult male rats induced a significant reduction in the GH-releasing hormone (GHRH; 2 micrograms/kg, i.v.)-induced peak GH rise, but only the 2.0 micrograms dose reduced also the GH-integrated area after administration of GHRH. This effect was absent after central administration of 20.0 micrograms GH/rat, due probably to leakage of some GH from the cerebral ventricle into the systemic circulation. Pretreatment with cysteamine (300 mg/kg, s.c.), a known depletor of hypothalamic SRIF, or with anti-SRIF serum (0.5 ml/rat) completely counteracted the lessening of the GH response to GHRH induced by 2.0 micrograms GH injected i.c.v. Similarly, pretreatment with the cholinergic agonist pilocarpine (3 mg/kg, i.v.) completely antagonized the inhibitory effect of central infusion of GH on the GHRH-induced GH response. Atropine (1.0 mg/kg, i.v.), a muscarinic cholinergic antagonist, strikingly inhibited the GHRH-induced GH rise, but when given in combination with i.c.v. infusion of GH there was no additive inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2897998 TI - Evidence for crosstolerance to the analgesic effects between morphine and selective alpha 2-adrenoceptor agonists. AB - Rats were injected subcutaneously (s.c.) with morphine (5 mg/kg) until tolerance developed to its antinociceptive action, or with 0.9% saline which was used as vehicle for morphine. Subsequently, both groups of animals were given an intrathecal (i.th.) dose of either noradrenaline (2 micrograms), clonidine (12.5 micrograms) or guanfacine (12.5 micrograms), that had been found previously to be reliably antinociceptive. In the saline-treated animals, these doses of noradrenaline, clonidine or guanfacine induced clear antinociceptive effects, but not in the morphine-group. It is therefore concluded that cross-tolerance to the antinociceptive effects of systemic morphine and the alpha-adrenoceptor agonists was obtained. The cross-tolerance between morphine on one hand, and noradrenaline, clonidine and guanfacine on the other, implies that a substantial opiate-adrenoceptor interaction exists in antinociceptive processes. PMID- 2897999 TI - Homospecific activity (activity per enzyme protein) of tyrosine hydroxylase increases in parkinsonian brain. AB - Tyrosine hydroxylase (TH) contents in the caudate nucleus, putamen, and substantia nigra from control and parkinsonism brains were measured for the first time by a sandwich enzyme immunoassay. Both the TH protein content and TH activity (Vmax) were decreased in parallel in the parkinsonian brains as compared with those of the control brains. In contrast, TH "homospecific activity" (activity per enzyme protein) was significantly increased in the parkinsonian brains. The results indicate that the decrease of TH activity in parkinsonian brains is due to the decrease of TH protein content as a result of cell death. The increase in the "homospecific activity" of residual TH in parkinsonian brain suggests such molecular changes in TH molecules as result in a compensatory increase in TH activity. PMID- 2898000 TI - Dose-dependent, K+-stimulated efflux of endogenous taurine from primary astrocyte cultures is Ca2+-dependent. AB - The K+-stimulated efflux of endogenous taurine from primary rat cerebellar astrocyte cultures prepared from 7-9-day-old rats was studied at 16-18 days in vitro using HPLC analysis. Taurine efflux was dose-dependent at K+ concentrations between 10 mM and 80 mM, with an EC50 of approximately 50 mM. Maximum stimulation of efflux above basal levels ranged from 56% at 10 mM K+ (204 pmol/min/mg protein) to 470% at 80 mM K+ (960 pmol/min/mg protein). Removal of Ca2+ from the buffer and the addition of either 1 mM EGTA or 10 mM Mg2+ abolished K+-stimulated efflux. Taurine efflux peaked and fell in parallel with the K+ concentration, but with an approximate lag of 3-5 min. The time course and amount of preloaded [3H]taurine released did not differ significantly from that seen for endogenous efflux. Basal taurine efflux varied inversely with the extracellular concentration of Ca2+ over the concentration range 0-5.0 mM. The observed Ca2+ dependence is consistent with a role for Ca2+ in the regulation of taurine release. Furthermore, taurine release from astrocytes in response to elevated K+ may reflect a neuromodulatory role for this amino acid in the CNS. PMID- 2898001 TI - Extracellular amino acid concentrations in the dorsal spinal cord of freely moving rats following veratridine and nociceptive stimulation. AB - In vivo microdialysis was used to sample extracellular concentrations of amino acids in the dorsal lumbar spinal cord of freely moving rats. Changes in the extracellular concentrations of amino acids were measured in response to infusion of veratridine (180 microM), a sodium channel activator, as well as during acute noxious stimulation by an injection of 5% formalin into the metatarsal region of the hindleg. Veratridine produced a tetrodotoxin (TTX)-sensitive increase in the extracellular concentration of Glu. Concentrations of Asp, taurine, Ala, Asn, and Gly were not significantly elevated following veratridine stimulation. Intradermal injection of formalin produced a TTX-sensitive increase in Asp concentration and a non-TTX-sensitive increase in Glu concentration. These data support the hypothesis that Glu and Asp are dorsal horn neurotransmitters involved in nociception. PMID- 2898002 TI - Solubilization of rat brain phencyclidine receptors in an active binding form that is sensitive to N-methyl-D-aspartate receptor ligands. AB - Phencyclidine (PCP) receptors were successfully solubilized from rat forebrain membranes with 1% sodium cholate. Approximately 58% of the initial protein and 20 30% of the high-affinity PCP binding sites were solubilized. The high affinity toward PCP-like drugs, the stereo-selectivity of the sites, and the sensitivity to N-methyl-D-aspartate (NMDA) receptor ligands were preserved. Binding of the potent PCP receptor ligand N-[3H][1-(2-thienyl)cyclohexyl] piperidine ([3H]TCP) to the soluble receptors was saturable (KD = 35 nM), and PCP-like drugs inhibited [3H]TCP binding in a rank order of potency close to that observed for the membrane-bound receptors; the most potent inhibitors were TCP (Ki = 31 nM) and the anticonvulsant MK-801 (Ki = 50 nM). The NMDA receptor antagonist 2-amino-5 phosphonovaleric acid inhibited binding of [3H]TCP to the soluble receptors; glutamate or NMDA diminished this inhibition in a dose-dependent manner. Taken together, the results indicate that the soluble PCP receptor preparation contains the glutamate recognition sites and may represent a single receptor complex for PCP and NMDA, as suggested by electrophysiological data. The successful solubilization of the PCP receptors in an active binding form should now facilitate their purification. PMID- 2898003 TI - Calcium homeostasis in digitonin-permeabilized bovine chromaffin cells. AB - The regulation of cytosolic calcium was studied in digitonin-permeabilized chromaffin cells. Accumulation of 45Ca2+ by permeabilized cells was measured at various Ca2+ concentrations in the incubation solutions. In the absence of ATP, there was a small (10-15% of total uptake) but significant increase in accumulation of Ca2+ into both the vesicular and nonvesicular pools. In the presence of ATP, the permeabilized cells accumulated Ca2+ into carbonyl cyanide m chlorophenyl hydrazone (CCCP)-sensitive and -insensitive pools. The CCCP sensitive pool--mainly mitochondria--was active when the calcium concentration was greater than 1 microM and was not saturated at 25 microM. The Ca2+ sequestered by the CCCP-insensitive pool could be inhibited by vanadate and released by inositol trisphosphate, a combination suggesting that this pool was the endoplasmic reticulum. The CCCP-insensitive pool had a high affinity for calcium, with an EC50 of approximately 1 microM. When the Ca2+ concentration was adjusted to the level in the cytoplasm of resting cells (0.1 microM), the presumed endoplasmic reticulum pool was responsible for approximately 90% of the ATP-stimulated calcium uptake. At a calcium level similar to the acetylcholine stimulated level in intact cells (5-10 microM), most of the Ca2+ (greater than 95%) went into the CCCP-sensitive pool. PMID- 2898005 TI - Effects of protonophores on the synthesis of catecholamines and the intracellular pH in cultured bovine adrenal medullary cells. AB - The protonophores carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) and carbonyl cyanide m-chlorophenylhydrazone (CCCP) stimulated the synthesis of 14C catecholamines from [14C]tyrosine in cultured bovine adrenal medullary cells. The stimulatory effect of CCCP but not of FCCP was partially dependent on extracellular Ca2+. CCCP but not FCCP increased the influx of 45Ca2+ to the cells. When cells were incubated with either CCCP or FCCP (0.01-0.2 microgram/ml), the intracellular pH fell from 7.2 to 6.3-6.5 and catecholamine synthesis increased. Tyrosine hydroxylase activity in a soluble fraction prepared from cultured adrenal medullary cells was measured after incubation of the cells with FCCP or CCCP. Although FCCP did not affect the activity of the enzyme, CCCP caused a stable activation of it which was dependent on extracellular Ca2+. Since the optimal pH of soluble tyrosine hydroxylase is around 6.0 in adrenal medullary cells, FCCP may increase the synthesis of catecholamines by shifting the intracellular pH toward it. In addition to this mechanism, CCCP may enhance the synthesis of catecholamines by a Ca2+-dependent mechanism. PMID- 2898004 TI - Inhibition by forskolin of excitatory amino acid-induced accumulation of cyclic AMP in guinea pig hippocampal slices. AB - The effect of forskolin on the excitatory amino acid-induced accumulation of cyclic AMP was examined in hippocampal preparations of the guinea pig. Forskolin at concentrations of 0.1-10 microM remarkably enhanced the stimulatory effects of histamine and adenosine, whereas it markedly attenuated the stimulation induced by cysteine sulfinate, an excitatory amino acid. Forskolin reduced the maximal response to cysteine sulfinate without affecting the apparent ED50. At a concentration of 1 microM, forskolin also inhibited the stimulatory effects of glutamate, N-methyl-DL-aspartate, and veratridine without affecting those of kainate and quisqualate. Pretreatment of the slices with 0.1 mM N-ethylmaleimide partially prevented the attenuation by forskolin of cysteine sulfinate-induced accumulation of cyclic AMP without affecting the stimulation induced by cysteine sulfinate. Forskolin at concentrations of less than 1 microM did not affect GTP stimulated activity and Cl- -dependent activity of adenylate cyclase of the hippocampal membranes. PMID- 2898006 TI - Evidence that aspartate aminotransferase activity and ketodicarboxylate carrier function are essential for biosynthesis of transmitter glutamate. AB - Based on the selective inhibition of glutamate release in cerebellar granule cells in primary cultures by the aspartate aminotransferase inhibitor, aminooxyacetic acid, and by the ketodicarboxylate carrier inhibitor, phenylsuccinate, a novel model for synthesis of transmitter glutamate is suggested: Glutamate is formed from glutamine in the mitochondrial intramembrane space by phosphate-activated glutaminase, transported across the inner membrane in exchange with aspartate, transaminated in the matrix to alpha-ketoglutarate, which via the ketodicarboxylate carrier is transferred to the cytoplasm, and transaminated to form transmitter glutamate. Such a mechanism would explain the functional role of aspartate aminotransferase in glutamatergic neurons. PMID- 2898007 TI - Alteration in fatty acid composition of adult rat brain capillaries and choroid plexus induced by a diet deficient in n-3 fatty acids: slow recovery after substitution with a nondeficient diet. AB - Wistar rats were fed for three generations with a semisynthetic diet containing either 1.5% sunflower oil (940 mg% of C18:2n-6, 6 mg% of C18:3n-3) or 1.9% soya oil (940 mg% of C18:2n-6, 130 mg% of C18:3n-3). At 60 days of age, the male offspring of the third generation were killed. The fatty acyl composition of isolated capillaries and choroid plexus was determined. The major changes noted in the fatty acid profile of isolated capillaries were a reduction (threefold) in the level of docosahexaenoic acid and, consequently, a fourfold increase in docosapentaenoic acid in sunflower oil-fed animals. The total percentage of polyunsaturated fatty acids was close to that in the soya oil-fed rats, but the ratio of n-3/n-6 fatty acids was reduced by threefold. In the choroid plexus, the C22:6n-3 content was also reduced, but by 2.6-fold, whereas the C22:5n-6 content was increased by 2.3-fold and the ratio of n-3/n-6 fatty acids was reduced by 2.4 fold. When the diet of sunflower oil-fed rats was replaced with a diet containing soya oil at 60 days of age, the recovery in content of n-6 and n-3 fatty acids started immediately after diet substitution; it progressed slowly to reach normal values after 2 months for C22:6n-5 and 2.5 months for C22:6n-3. The recovery in altered fatty acids of choroid plexus was also immediate and very fast. Recovery in content of C22:5n-6 and C22:6n-3 was complete by 46 days after diet substitution. PMID- 2898008 TI - Identification of alpha 2-adrenergic receptors in chicken pineal gland using [3H]rauwolscine. AB - The norepinephrine-induced inhibition of avian pineal N-acetyltransferase activity appears to be mediated by alpha 2-adrenergic receptors. In this study, alpha 2-adrenergic receptors in the chicken pineal gland were directly identified by radioligand binding. Membrane preparations of pineal glands from chickens from 1 to 6 weeks of age were examined using [3H]rauwolscine, a selective alpha 2 adrenergic receptor antagonist, to characterize the binding sites. The results indicate no ontological change in either the affinity (KD) or density of receptor binding sites (Bmax) during the time span examined. The binding was saturable and of high affinity with a mean KD of 0.27 +/- 0.01 nM and a mean Bmax of 242 +/- 12 fmol/mg protein. Further characterization of these binding sites indicated that the alpha 2-adrenergic receptor is of the alpha 2A subtype, since prazosin and ARC-239 bound with low affinities and oxymetazoline bound with high affinity. PMID- 2898009 TI - Modified taxols, 4. Synthesis and biological activity of taxols modified in the side chain. AB - A number of taxol derivatives substituted at the 2' position of the side chain have been prepared and their biological activities determined in KB cell culture and/or the P-388 in vivo assay. The 2'-(t-butyldimethylsilyl)taxol 5 is essentially inactive, indicating the need for a free hydroxyl group at the 2' position for activity. Epimerization of the 2' position occurred on treatment of 2'-acetyltaxol derivatives with 1,5-diazabicyclo[5.4.0]undec-7-ene, but treatment of 2'-(2,2,2-trichloroethyloxycarbonyl) taxol derivatives with DBU yielded the novel cyclization products 11 and 12 and, after deprotection at the 7 position, 13. The derivative 13 is also essentially inactive in the KB test system. Two taxols with increased H2O solubility were prepared, the 2'-(beta-alanyl) derivative 15 and the 2'-succinyl derivative 16. Although both these derivatives were active in vivo and in vitro, the former was too unstable and the latter not active enough to make suitable H2O-soluble derivatives of taxol. PMID- 2898010 TI - Aspartic acid aminotransferase activity is increased in actively spiking compared with non-spiking human epileptic cortex. AB - Increased concentration of the excitatory neurotransmitter aspartic acid in actively spiking human epileptic cerebral cortex was recently described. In order to further characterise changes in the aspartergic system in epileptic brain, the behaviour of aspartic acid aminotransferase (AAT), a key enzyme involved in aspartic acid metabolism has now been examined. Electrocorticography performed during surgery was employed to identify cortical epileptic spike foci in 16 patients undergoing temporal lobectomy for intractable seizures. Patients with spontaneously spiking lateral temporal cortex (n = 8) were compared with a non spiking control group (n = 8) of patients in whom the epileptic lesions were confined to the hippocampus sparing the temporal convexity. Mean activity of AAT in spiking cortex was significantly elevated by 16-18%, with aspartic acid concentration increased by 28%. Possible explanations for the enhanced AAT activity include increased proliferation of cortical AAT-containing astrocytes at the spiking focus and/or a generalised increase in neuronal or extraneuronal metabolism consequent to the ongoing epileptic discharge. It is suggested that the data provide additional support for a disturbance of central excitatory aspartic acid mechanisms in human epileptic brain. PMID- 2898011 TI - Topographical distribution of neurochemical changes in Alzheimer's disease. AB - Biochemical indices of cortical nerve cells affected in Alzheimer's disease have been proposed (excitatory dicarboxylic amino acid, EDAA, sodium-dependent carrier; phosphate-activated glutaminase activity; serotonin type 2 recognition site; somatostatin-like immunoreactivity). These and the content of EDAAs and two related amino acids, and choline acetyltransferase (ChAT) activity have been measured in up to 13 areas of cerebral cortex and the cerebellar cortex from 16 patients with Alzheimer's disease and 17 controls. Reduction of the index of the serotonin recognition site, somatostatin content and another biochemical index of interneurones coincide and indicate a rather unexpected focal loss of such neurones from the parietal lobe. No unequivocal measure of the integrity of pyramidal neurones could be established as the content of no amino acid was reduced, the index of the EDAA carrier showed evidence of change in few brain regions and glutaminase activity was subject to unexplained variability. ChAT activity alone closely paralleled a previous report of the distribution of morphological degeneration. The results are discussed in relation to therapy and positron emission tomography. PMID- 2898012 TI - Effects of alpha- and beta-adrenergic agonists on Trypanosoma cruzi interaction with host cells. AB - We studied the effects of adrenergic agonists on the capacity of blood trypomastigote forms of Trypanosoma cruzi to associate with (i.e., bind and/or penetrate) host cells in vitro. The extent of T. cruzi association with mouse macrophages in the presence of the beta-adrenergic agonist L-isoproterenol was significantly decreased with respect to mock-treated controls. Similar results were obtained when the parasite was pretreated with L-isoproterenol and was then allowed to interact with untreated macrophages. In contrast, pretreatment of trypomastigotes with either L-phenylephrine or methoxamine-alpha-adrenergic agonists--enhanced their reactivity with macrophages. Interaction with a nonphagocytic host cell was also decreased and increased by parasite pretreatment with beta- and alpha-adrenergic agonists, respectively. The L-isoproterenol and L phenylephrine effects were no longer detectable 2 and 3 hr after their removal, respectively, and were therefore reversible. Atenolol, a specific beta 1 adrenoreceptor blocker inhibited the L-isoproterenol effect, whereas butoxamine, a specific beta 2 blocker, did not. Thus, beta 1-like but not beta 2-like binding sites appeared to be expressed on T. cruzi. Both prazosin and yohimbine, preferential alpha 1- and alpha 2-receptor blockers, respectively, abolished the L-phenylephrine effect. The opposite effects of alpha- and beta-adrenergic agonists suggested that the infectivity of T. cruzi may be regulated by activation of surface components comparable to the adreno-receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898013 TI - Morphologic effects of unilateral cryptorchidism on the contralateral descended testis. AB - Unilateral cryptorchidism is frequently accompanied by infertility. Uncertainty exists as to whether the infertility is a genetic effect or is related to an autoimmune reaction to the elevated testis. The effects of unilateral cryptorchidism were evaluated in 50 mice by surgically elevating the left testicle of 21-day-old mice into the abdomen (AT). A sham operation was performed on the left testicle of 50 control mice (SHT). The temperature of the abdominal testes measured 2.5 degrees C higher than the scrotal testes. The testes were removed from both sides at 1, 2, 3, 4 and 6 weeks postoperation. After testicular weights were recorded, seminiferous tubule diameters were measured, and germinal epithelium maturity was graded histologically using a modified Johnson testicular biopsy score. Progressive abnormal changes were seen in the contralateral descended testicles of AT as compared to SHT. By 3 weeks, though testicular weight changes were similar, mean seminiferous tubule diameter was smaller (P less than .001), and the germinal epithelium was less mature (P less than .001). These changes persisted through the sixth week. By changing the physiologic environment of one testicle, we have induced alterations in the histologic appearance of the contralateral testicle during the period of normal maturation. PMID- 2898014 TI - Clinical classification for undescended testes: experience in 1,010 orchidopexies. AB - A clinical classification for undescended testes based on location, size, and mobility of the testis in the inguinal canal was performed. The latter was artificially divided into three sections. The lower portion was considered position I; the mid part, position II; the upper part, position III; and the abdominal (nonpalpable) part, position IV). Normal-size testes were considered as being size A; testes reduced up to 30% in volume, size B; and gonads reduced more than 30% of the estimated normal, size C. According to these criteria, a case of chryptorchidism can then be classified as I, II, III, or IV and A, B, or C and fixed or movable. This classification was used in 1,010 orchidopexies conducted under a uniform surgical technique by the same surgeon and followed annually up to a maximum of 23 years. Retractile testes were excluded from this series. In most cases, the clinical diagnosis matched the surgical findings. Results are presented in two groups, unilateral and bilateral, since the main problem for the latter is fertility, and they should be considered separately in any study. For both groups, the most frequent finding was the normal-sized testis (size A), in location I. For positions II and III, size B was the most common; and in position IV (intraabdominal), size C had a substantially higher incidence. Surgical technique was simpler and the outcome better, as expected, when the testicles were of good size, located in a low position, and operated at an early age. A worthwhile finding was the long-term cosmetic improvement in an important percentage of the surgically descended B-sized testes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898015 TI - Omphalocele, cryptorchidism and brain malformations. PMID- 2898016 TI - In vitro study on corneal permeability to bunazosin. AB - Corneal permeability of bunazosin, one of the alpha-adrenergic receptor antagonists, was investigated in vitro using excised rabbit cornea mounted on a corneal permeability apparatus, and the enhancing effects of various acids on the permeability of bunazosin were evaluated. Caprylic and capric acid elevated octanol/water partition coefficient of bunazosin, and corneal permeability was increased, probably as a result of ion-pair formation between them. Neither bunazosin, these acids, or the ion-pair caused corneal swelling. These acids, in contrast, had little effect on the partition of pilocarpine, or on corneal permeability. PMID- 2898017 TI - Update on tocolytic therapy in the management of preterm labor. PMID- 2898018 TI - Doppler ultrasonography as a guide to management in Takayasu's arteritis. PMID- 2898019 TI - Adverse reaction to sulfasalazine. PMID- 2898020 TI - [Recent advances in neuroendocrinology]. PMID- 2898021 TI - Polydrug abuse among Ethiopian university students with particular reference to khat (Catha edulis). AB - The pattern of use of khat (Catha edulis Forsk), alcohol, cigarettes and tranquillizers among 479 medical and paramedical students in a boarding college in northwestern Ethiopia was studied by an anonymous self-administered questionnaire. The survey coverage rate was 98.8%. The majority of students were males (82.6%) and their average age was 21.2 years. The prevalence rate of current use of alcohol, cigarettes, khat and tranquillizers was 31.1%, 26.3%, 22.3% and 7.7%, respectively. These substances were also used in combinations, the most frequent involved khat, alcohol and cigarettes. Use of khat varied by the type of training (medical/paramedical) and by phase of medical education (preclinical/clinical). These variations were also apparent when data were analysed by sex and frequency of khat use. It appears that the pattern of khat use among university students is similar to that reported for substance abuse in other countries. Because of the economic importance of khat in the Ethiopian economy, its control may be difficult at present. PMID- 2898022 TI - A review of surgical treatment of undescended testes with emphasis on anatomical position. AB - We reviewed our 5-year surgical experience with undescended testes in 295 patients. Surgery had been performed in a standardized fashion to identify accurately testicular position. Before opening the fascia of the external oblique muscle, the superficial inguinal pouch and area beyond the external ring were explored carefully. Testes beyond the external ring were defined as ectopic. Other positions identified included intracanalicular and intra-abdominal. Of 336 testes 66 per cent were ectopic, 16 per cent intracanalicular, 10 per cent abdominal and 3 per cent absent. Maldescent was unilateral in 254 patients and bilateral in 41. In the unilateral cases of 178 testes were ectopic (70 per cent) and the testis was palpable preoperatively in 158 (89 per cent). Bilateral undescended testes were palpable on both sides preoperatively in 25 of 41 cases (61 per cent), including 16 (64 per cent) ectopic testes. There were 10 cases of bilateral nonpalpable testes and in 8 (80 per cent) both testes were intra abdominal. Based on the high incidence of ectopic testes and their associated abnormal attachments, it is our prediction that nonsurgical treatment (hormonal) of undescended testes would not be expected to achieve optimal results. PMID- 2898023 TI - This month in Investigative Urology: what makes bacteria stick to the bladder mucosa? PMID- 2898024 TI - Effects of five alpha-blockers on the hypogastric nerve stimulation of the canine lower urinary tract. AB - Electrical stimulation of the hypogastric nerve increased both urethral and bladder pressures of anaesthetized male dogs, without affecting cardiovascular parameters. Intravenous injections of prazosin, phentolamine, thymoxamine, phenoxybenzamine and yohimbine inhibited the urethral pressure increase in a dose dependent manner, but the increase in bladder pressure was not modified by these alpha-blockers. PMID- 2898026 TI - Leads from the MMWR. Syrup of ipecac contamination. PMID- 2898025 TI - Diabetic retinopathy after two years of intensified insulin treatment. Follow-up of the Kroc Collaborative Study. The Kroc Collaborative Study Group. AB - The progression of retinopathy was reevaluated at two years in 64 of the 68 patients with mild to moderate diabetic retinopathy, originally randomly assigned for an eight-month period either to intensified diabetic control with continuous subcutaneous insulin infusion (CSII) or to unchanged conventional injection treatment. Twenty-three of the 34 patients in the former group and 24 of the 34 in the latter agreed to continue to follow their original treatment assignment for a further 16 months. The others crossed over at the end of the first eight months of the study. During those first eight months, substantial lowering of blood glucose concentration had been achieved in the CSII group, unexpectedly associated with evidence of accelerated progression of retinopathy compared with the conventional injection treatment group. Glycemic separation was maintained at two years between the two groups continuing to receive the assigned treatment; during this time the mean retinopathy level deteriorated with conventional injection treatment and improved with CSII. At two years the degree of retinopathy in the two treatment groups was indistinguishable, with some trend to lesser overall deterioration with CSII. It is concluded that, in diabetics with mild to moderate nonproliferative retinopathy, the acceleration in activity associated with tightened control is not sustained and does not initiate vasoproliferative deterioration in retinopathy. PMID- 2898027 TI - A multicenter comparison of lovastatin and cholestyramine therapy for severe primary hypercholesterolemia. The Lovastatin Study Group III. AB - This study compares lovastatin and cholestyramine resin therapy in patients with severe primary hypercholesterolemia. Two hundred sixty-four patients on lipid lowering diets were randomized equally to receive 12 g of cholestyramine resin, 20 mg of lovastatin, or 40 mg of lovastatin, each twice a day. The mean reductions among the three groups after 12 weeks' treatment in levels of total plasma cholesterol (-17%, -27%, and -34%, respectively) and low-density lipoprotein cholesterol (-23%, -32%, and -42%, respectively) and the median reductions in apolipoprotein B levels (-21%, -28%, and -33%, respectively) were all significantly different between groups. Similar mean increases in high density lipoprotein cholesterol levels (8%, 9%, and 8%, respectively) and median increases in apolipoprotein A-1 levels (7%, 6%, and 11%, respectively) were observed in all treatment groups. Cholestyramine resin treatment had no significant effect on very low-density lipoprotein cholesterol and apolipoprotein A-II levels and produced a median 11% increase in plasma triglyceride concentration; in contrast, administration of either 20 or 40 mg of lovastatin twice a day was associated with median reductions in very low-density lipoprotein cholesterol levels (-34% and -31%, respectively) and plasma triglyceride levels ( 21% and -27%, respectively) and median increases in levels of apolipoprotein A-II (8% and 13%, respectively). Adverse events in all treatment groups were preponderantly in the gastrointestinal tract; gastrointestinal tract symptoms that could be attributed to therapy with a specific drug occurred in 58% of the cholestyramine resin group, 13% of the 20-mg lovastatin group, and 14% of the 40 mg lovastatin group. The only drug-attributable serious adverse event was a reversible myopathy in a patient taking 40 mg of lovastatin twice a day. We conclude that lovastatin is both more effective and better tolerated than cholestyramine resin in the treatment of primary hypercholesterolemia. PMID- 2898028 TI - [Colitis--recent trends and countermeasures. Mycoses, protozoan and parasitic diseases]. PMID- 2898030 TI - Properties of phenytoin binding sites in the rat brain: regional distribution and postnatal development. AB - Specific [3H]phenytoin binding in rat cortical membranes is associated with a micromolar affinity site through which diazepam can exert an enhancing effect. In contrast to diazepam, (+)bicuculline, isoguvacine and pentobarbital inhibited phenytoin binding, while GABA and (-)baclofen had no effect. Decreased phenytoin binding and a loss of the diazepam effect were observed in phospholipase A2 treated membranes. Binding in the absence and presence of diazepam demonstrated differential postnatal development. Furthermore, the degree to which binding was enhanced by diazepam varied from one brain region to another. The regional variations of phenytoin binding, both in the presence and absence of diazepam, did not correlate positively with the regional distribution of either the central benzodiazepine receptors or the peripheral type binding sites in the brain. PMID- 2898029 TI - Reclassification of leukemia among A-bomb survivors in Nagasaki using French American-British (FAB) classification for acute leukemia. AB - The concordance rate for diagnoses of atomic bomb-related cases of leukemia in Nagasaki was determined using the French-American-British (FAB) classification for acute leukemias and myelodysplastic syndromes (MDS). Two Radiation Effects Research Foundation (RERF) hematologists and one of the members (JMB) of the FAB cooperative group reviewed independently the peripheral blood and/or bone marrow smears from 193 people with leukemia or a related disorder. There was 85% agreement in the identification of types and subtypes of acute leukemia. There was almost complete agreement for the diagnoses of non-FAB disorders (chronic myeloid leukemia (CML), adult T-cell leukemia (ATL) and others) resulting in overall concordance of 88.2%. The present study suggests that the previously established leukemia types for about a quarter of the cases of acute leukemia and related disorders except CML should be changed. Considerable numbers of cases of ATL and MDS were involved in this series. The frequency of the former disease was not high in the high-dose irradiated group, but that of the latter was considerably high. All subtypes of AML except M3 and M6 were present in the high dose group. The striking difference in CML incidence between Nagasaki and Hiroshima may continue to be a problem in relation to biological response to radiation exposure. PMID- 2898031 TI - Effects of various drugs on superoxide generation, arachidonic acid release and phospholipase A2 in polymorphonuclear leukocytes. AB - The effects of variety of drugs on metabolic burst and phospholipase A2 in polymorphonuclear leukocytes (PMNs) were investigated. The stimulation of PMNs by n-formyl-methionyl-leucyl-phenylalanine (FMLP) causes arachidonic acid (AA) to be released in the cells concomitantly with the generation of superoxide anion. These variables were effectively diminished with some clinically employed drugs including chlorpromazine, trifluoperazine, azelastine, clemastine and mepacrine at the lower concentration of 20 microM. In contrast, indomethacin and procaine were ineffective even at the higher concentration of 100 microM. Subcellular fractionation of PMNs revealed that phospholipase A2 activity was located both in the plasma membrane-rich fraction as well as the granule-microsome-rich fraction, and the potency of inhibition of membrane-bound phospholipase A2 by the above mentioned drugs was: indomethacin (IC50 = 3 microM) less than chlorpromazine less than azelastine and clemastine (IC50 greater than 100 microM). The low potency of antipsychotropic drugs and antihistaminic drugs in inhibiting the fractionated phospholipase A2 contrast with the high efficiency with which they inhibit the superoxide generation and the AA release from stimulated PMNs. The AA releases from the PMNs stimulated by FMLP or calcium ionophore (A23187) were almost equally diminished by various drugs at the lower concentration. From these observations, it appeared likely that these drugs might inhibit the metabolic stimulations of PMNs at the sites of the Ca2+-dependent activation processes of the enzymes responsible for the AA release and the superoxide generation. PMID- 2898032 TI - Palytoxin-induced K+ efflux from ileal longitudinal smooth muscle of the guinea pig. AB - In guinea-pig ileal longitudinal smooth muscle, both palytoxin (PTX) and carbachol (CCh) increased K+ efflux with an EC50 of 1.8 X 10(-10) M and 4.1 X 10( 7) M, respectively. Atropine (10(-6) M) did not inhibit the K+ efflux due to PTX (3 X 10(-9) M), but completely inhibited the efflux due to CCh (10(-5) M). External Ca2+ removal and verapamil (10(-5) M) did not change the PTX-induced K+ efflux, although the CCh-induced K+ efflux was inhibited about 77% and 71%, respectively. PTX-induced K+ efflux was reduced to 31% by a depletion of intracellular Ca2+. Tetraethylammonium (15 mM) inhibited the K+ efflux due to PTX or CCh to 61% or 75%, respectively. The PTX-induced K+ efflux was also inhibited by cymarin (3 X 10(-8) M), ouabain (10(-5) M) and digitoxin (10(-5) M). These results suggest that the PTX-induced K+ efflux is less dependent on Ca2+ influx than that due to CCh. Furthermore, the binding sites for PTX in the ileal muscle of guinea-pig may be Na+, K+-ATPase, as has been suggested in other types of cells. PMID- 2898033 TI - Interaction of SM-3997 with serotonin receptors in rat brain. AB - The propensity of SM-3997 to displace 3H-ligands was tested in vitro in a number of receptor-binding assays. SM-3997 possessed a high affinity towards 5-HT1A receptors, low affinity towards dopamine (D2) and 5-HT2 receptors, and no affinity towards benzodiazepine (BZ), GABA, 5-HT1B and adrenergic receptors. Moreover, SM-3997 facilitated neither 3H-flunitrazepam binding nor 3H-muscimol binding. These results suggest that the action of SM-3997 may be mediated via central 5-HT1A receptors but not the BZ-GABA receptor complex. PMID- 2898034 TI - Comparison of the effects of benzodiazepine and nonbenzodiazepine anxiolytics on mouse-killing behavior in rats. AB - The present study investigated the effects of nonbenzodiazepine anxiolytics on mouse-killing behavior in rats, compared with the effects of benzodiazepine anxiolytics. Mouse-killing behavior was induced by bilateral olfactory bulbectomy. The following drugs were administered intraperitoneally: chlordiazepoxide, diazepam, ethyl loflazepate, fludiazepam, zopiclone, suriclone, and CL 218,872. Among these drugs, suriclone (ED50 = 1.3 mg/kg) and fludiazepam (ED50 = 5.9 mg/kg) showed potent suppressive effects. Diazepam, ethyl loflazepate, and CL 218,872 showed only weak actions on mouse-killing behavior. PMID- 2898035 TI - [Microflora of the drinking water regenerated from atmospheric moisture condensate in hermetically sealed quarters]. AB - In an enclosed environment the species composition of microorganisms was quantified and metabolic processes in microbial cells isolated from the atmospheric condensate and reclaimed water were investigated. It was demonstrated that indicator microorganisms isolated from water and condensate samples (Alcaligenes faecalis, Citrobacter freundii, Aeromonas hydrophila, Acinetobacter Moraxella) were specific and differed from indicator microorganisms typical of regular tap water. PMID- 2898036 TI - [Interrelation between changes in bone mass and the hematopoietic stem cell count]. PMID- 2898037 TI - Fast black K salt: a visualization reagent for thin-layer chromatography of beta adrenergic blocking drugs. AB - A sensitive visual method for the thin-layer chromatography of beta-adrenergic blocking drugs is described. The Rf values and the detection limits of eleven beta-blockers extracted from urine and as pure drugs are given. Other commonly used cardiovascular drugs are shown not to interfere with the method. The procedure is applicable to both urine and liver extracts. PMID- 2898038 TI - Gastric somatostatin release: evidence for direct mediation by calcitonin gene related peptide and vasoactive intestinal peptide. AB - It has previously been demonstrated that somatostatin (SRIF) directly inhibits parietal cell secretion. However, the significance of SRIF as a paracrine agent and mechanisms of local gastric SRIF release are not clear. Vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) are neuropeptides which have been localized in the gastric fundus and have been demonstrated to inhibit gastric acid secretion in vivo. The present study examines the hypothesis that CGRP and VIP act via the release of gastric fundic SRIF. The study utilized rabbit isolated gastric glands prepared by collagenase digestion. Glands were incubated alone, or with 10(-10)-10(-6) M CGRP or 10(-10)-10(-6) M VIP for 30 min. Supernatant SRIF was measured using a specific radioimmunoassay. Unstimulated SRIF release was 101 +/- 16 fmole/ml. CGRP (10(-7) and 10(-6) M) and VIP (10(-7) and 10(-6) M) resulted in significant SRIF release. The maximum release of SRIF by CGRP (506 +/- 113 fmole/ml) was significantly greater than that by VIP (293 +/- 33 fmole/ml) (P less than 0.05). However, both these concentrations of SRIF are comparable to the ID50 concentration (4.5 X 10(-10) M) for SRIF inhibition of acid secretion by isolated parietal cells as assessed by [14C]aminopyrine accumulation. These results are consistent with the hypothesis that CGRP and VIP inhibition of acid secretion may be mediated, at least in part, by the local release of SRIF from the gastric fundus. These data further support the significance of paracrine interactions in the modulation of cellular secretory function. PMID- 2898040 TI - [Terfenadine (Teldanex)--a review of its adverse effects a year after registration]. PMID- 2898039 TI - Intestinal alkaline phosphatase isoenzyme in patients with primary liver cancer during treatment with N10-propargyl 5, 8-dideazafolic acid (CB 3717). AB - Serum aspartate transaminase (AST), alkaline phosphatase (ALP), and gamma glutamyl transferase (gamma GT) activities and the serum ALP isoenzyme pattern have been measured in eleven patients undergoing treatment with CB3717. There were increases in the activity of all three enzymes. The ALP isoenzyme pattern showed an increased contribution of the intestinal isoenzyme to the serum ALP activity. This may be due to increased intestinal mucosal leakage or impaired uptake and breakdown of the intestinal isoenzyme by the liver. PMID- 2898041 TI - Induction of B-type receptors for platelet-derived growth factor in vascular inflammation: possible implications for development of vascular proliferative lesions. AB - Expression of B-type receptors for platelet-derived growth factor (PDGF) in frozen sections of blood vessels from tissues affected by abnormal vascular cell proliferation was investigated by immunohistochemical techniques and compared with expression of these receptors in blood vessels of normal tissues. Receptors were not expressed, or expressed at low levels, in vessels of normal tissues. In contrast, a pronounced expression of PDGF B-type receptors was seen on vascular smooth muscle cells in atherosclerotic plaques, rejected kidneys, and chronic synovitis. These observations suggest induction of PDGF B-type receptors on vascular smooth muscle cells in inflamed tissues, which would render such cells responsive to growth stimulation by PDGF released from captured platelets, or produced locally (eg, by inflammatory cells or smooth muscle cells). Autocrine or paracrine stimulation of cell growth caused by the effect of PDGF on cells with induced receptors may be important in the formation of the proliferative lesions found in atherosclerosis and in certain forms of chronic inflammation. PMID- 2898042 TI - Simple non-invasive method to obtain DNA for gene analysis. AB - A technique is described which demonstrates that sufficient human DNA for direct gene analysis can be isolated from buccal epithelial cells obtained by mouthwash. This procedure is much simpler and cheaper than existing methods and, combined with DNA amplification by polymerase chain reaction, should allow community screening for carrier status for single gene defects such as cystic fibrosis. PMID- 2898043 TI - Novel modes of action of aminoglycoside antibiotics against Pseudomonas aeruginosa. AB - Several mucoid strains and one non-mucoid strain of Pseudomonas aeruginosa were grown in subinhibitory concentrations of various aminoglycosides, beta-lactams, and ciprofloxacin. At antibiotic concentrations that did not affect bacterial growth, aminoglycosides inhibited the excretion of alginate capsule and the production of the iron-chelating siderophores. The same concentrations also disturbed other aspects of the bacterium's iron metabolism, manifested by reduced cellular levels of cytochromes and catalase. beta-lactams, except for cefotaxime, and ciprofloxacin did not reduce alginate excretion. These effects on virulence factors are likely to contribute to the efficacy of aminoglycosides. PMID- 2898044 TI - Rapid diagnosis of cytomegalovirus infection by in-situ hybridisation in liver grafts. AB - Cytomegalovirus (CMV) is a major cause of hepatic dysfunction after liver transplantation, but proof of infection and distinguishing CMV hepatitis from other causes of impaired liver function can be difficult. In-situ hybridisation for CMV-DNA in liver biopsy specimens was assessed in 25 liver graft recipients in whom CMV was suspected on clinical grounds. CMV-DNA was detected in all 10 patients with primary CMV infection, in whom a close correlation was found between the number of CMV-DNA-positive cells and both the number of cells containing viral inclusions identified by light microscopy and the clinical severity of disease. In contrast, CMV-DNA was not detected in patients with secondary CMV infection, or in those without evidence of CMV infection. In-situ hybridisation for CMV-DNA provides an accurate and rapid diagnosis of CMV infection, and allows specific antiviral therapy to be used earlier. PMID- 2898045 TI - Effect of intranasal glucagon on blood glucose levels in healthy subjects and hypoglycaemic patients with insulin-dependent diabetes. AB - Glucagon in solution with a surfactant (deoxycholic acid 1% w/v) was administered by intranasal spray to 6 healthy fasting subjects and 6 insulin-dependent diabetics with insulin-induced hypoglycaemia. In the normal subjects, intranasal glucagon increased plasma glucose levels, with a dose-response effect. In the diabetic patients, plasma glucose levels showed a mean increase of 100% above nadir values in approximately 26 min in response to 7.5 mg intranasal glucagon; hypoglycaemic symptoms were relieved within about 7 min. These results suggest that intranasal glucagon is effective and may represent an alternative to parenteral glucagon or glucose or to oral sugar as the first-line treatment of hypoglycaemic episodes in insulin-dependent diabetics. PMID- 2898046 TI - Pathogenesis of non-traumatic fat embolism. AB - Like the liposomes of certain intravenous fat emulsions associated with embolic effects in acutely ill patients, chylomicrons and very low density lipoproteins (VLDL) show calcium-dependent agglutination by C-reactive protein (CRP). It is suggested that non-traumatic fat embolism may be caused by agglutination of chylomicrons and VLDL by high levels of plasma CRP. This mechanism may also cause acute pancreatitis in patients with types I, IV, and V hyperlipidaemia, and avascular necrosis of bone in patients with corticosteroid-induced hyperlipidaemia. PMID- 2898047 TI - Prophylactic sclerotherapy of oesophageal varices: is it justified? PMID- 2898048 TI - Ciliary dyskinesia and ultrastructural abnormalities in respiratory disease. PMID- 2898049 TI - DNA diagnosis and the polymerase chain reaction. PMID- 2898051 TI - Blood in the alcohol stream--revisited. PMID- 2898050 TI - Critical questions: critical incidents; critical answers. PMID- 2898053 TI - Allogeneic bone marrow transplantation for leukaemia in Europe. Report from the Working Party on Leukaemia, European Group for Bone Marrow Transplantation. AB - 1957 allogeneic HLA-identical sibling-donor bone-marrow transplants done in 52 European centres between 1979 and 1986 and reported to the European bone-marrow transplant leukaemia registry were analysed. The most important factor influencing leukaemia-free survival, transplant-related mortality, and relapse incidence was the stage of the disease at the time of the transplant. This dominant role of the stage of the disease in all three diagnostic categories- acute myeloblastic leukaemia, acute lymphoblastic leukaemia, and chronic myeloid leukaemia--for all three end-points clearly indicates that resistance of the leukaemia cell to the procedure is more important than bulk of the disease. Additional prognostic factors for leukaemia-free survival and transplant-related mortality were age of the patient, cyclosporin for preventing graft-versus-host disease, and the donor-recipient sex combination. The risk of relapse was highest in patients with acute lymphoblastic leukaemia. In a multivariate analysis leukaemia-free survival was similar for all three major diagnostic categories and has not changed since the introduction of the European registry in 1979. These results show that the biological differences between the three main diagnostic categories of leukaemia are not as great as had been assumed and that the traditional approaches to improving results in recent years have failed. PMID- 2898054 TI - Combined therapies for upper gastrointestinal disorders--any advantage? PMID- 2898052 TI - Impact of B subunit killed whole-cell and killed whole-cell-only oral vaccines against cholera upon treated diarrhoeal illness and mortality in an area endemic for cholera. AB - The impact of B subunit killed whole-cell (BS-WC) and killed whole-cell-only (WC) oral cholera vaccines was assessed in a randomised double-blind trial in rural Bangladesh. 62,285 children aged 2-15 years and women aged over 15 ingested three doses of one of the vaccines or placebo. During the first year of follow-up there was a 26% reduction of all visits for treatment of diarrhoea in the BS-WC group and a 22% reduction in the WC group. The reduction of all admissions for fatal or severely dehydrating diarrhoea was 48% in the BS-WC group and 33% in the WC group. Overall mortality rates were 26% lower in the BS-WC group and 23% lower in the WC group during the first year, and reductions of mortality were observed only in women vaccinated at ages over 15 years. However, no differences in cumulative mortality were evident at the end of the second year of surveillance. PMID- 2898055 TI - Gallstones and glaciers: the stone that came in from the cold. PMID- 2898056 TI - Iodine-deficiency disorders. PMID- 2898057 TI - Selective decontamination in intensive therapy units. PMID- 2898058 TI - Fish oil. PMID- 2898059 TI - Jaundice in patients with gallstones: choledocholithiasis or hepatitis? PMID- 2898060 TI - Complete thrombolysis of mesenteric vein occlusion with recombinant tissue-type plasminogen activator. PMID- 2898061 TI - Mechanical ventilation for the newborn. PMID- 2898062 TI - Severity of anaemia and operative mortality and morbidity. PMID- 2898063 TI - Specific IgE antibodies to Bordetella pertussis after immunisation in infancy. PMID- 2898065 TI - Anonymous testing of women attending antenatal clinics for evidence of infection with HIV. PMID- 2898064 TI - Mediterranean spotted fever presenting as acute leucocytoclastic vasculitis. PMID- 2898066 TI - Breast feeding and HIV infection. PMID- 2898067 TI - HIV transmission by oral sex. PMID- 2898068 TI - Pentamidine: which salt? PMID- 2898069 TI - Overdiagnosis of infective endocarditis. PMID- 2898070 TI - Respiratory syncytial virus infections in adult bone marrow transplant recipients. PMID- 2898071 TI - Dual infection with leptospira and hantavirus. PMID- 2898072 TI - Serological distinction between primary rubella and reinfection. PMID- 2898073 TI - Child abuse registers. PMID- 2898074 TI - Magic of p values. PMID- 2898075 TI - Carcinoembryonic antigen. PMID- 2898077 TI - Pancreas transplantations. PMID- 2898076 TI - Occupational benzene exposure: preventable deaths. PMID- 2898078 TI - Clinical downstaging of uterine cervix by paramedical personnel. PMID- 2898079 TI - Galactosylation of IgG associated oligosaccharides. PMID- 2898081 TI - Radiation-induced cancer risks. PMID- 2898080 TI - Leukaemia and Dounreay. PMID- 2898082 TI - Non-surgical treatment of ectopic pregnancy. PMID- 2898083 TI - Antibiotic resistance in Escherichia coli from patients on sulphasalazine. PMID- 2898084 TI - Acute leukaemia during pregnancy. PMID- 2898085 TI - Analgesia during general anaesthesia. PMID- 2898086 TI - Papillomavirus infection and progress to abnormal cervical smears. PMID- 2898087 TI - Desferrioxamine, anaemia, and haemodialysis. PMID- 2898088 TI - Carotid artery disease presenting as cough headache. PMID- 2898089 TI - Lessons from an anaesthetic accident. PMID- 2898090 TI - AIDS in the UK and globally. PMID- 2898091 TI - Uropathogenic Escherichia coli can express serologically identical pili of different receptor binding specificities. AB - Uropathogenic Escherichia coli frequently express P-pilus adhesins that recognize Gal alpha (1-4)Gal-containing glycoconjugates. The P-pilus adhesin of the E. coli isolate J96 is encoded by the pap gene cluster and has been shown to agglutinate P1-erythrocytes. We now describe a novel gene cluster from J96, prs, which is responsible for the agglutination of sheep erythrocytes. The structurally related gene clusters both expressed pili exhibiting the F13 antigen. Analysis of mutants of cloned prs sequences, together with trans-complementation of pap and prs genes, identified the sheep-specific adhesin as the 37-kD PrsG protein. The prsG gene occupies the equivalent position in prs as occupied by papG, which specifies the Gal alpha (1-4)Gal-specific adhesin of pap. PrsG was shown to be structurally distinct from PapG since PapG-specific antiserum did not cross-react with PrsG. Using a solid phase glycolipid receptor binding assay, PrsG was found to specify preferential binding to the Forssman antigen, a major constituent of sheep erythrocyte membranes. The binding epitope was identified as the GaINAc alpha (1 3)GaINAc moiety. This is the first direct evidence that serologically identical pili may present antigenically distinct adhesins, each capable of binding to a specific receptor. PMID- 2898092 TI - [Hypokalemia and intestinal pseudo-obstruction in a 57-year-old male. Surgically confirmed VIPoma with reference to therapy with somatostatin]. PMID- 2898093 TI - [Clostridium perfringens infection with pronounced hemolysis]. PMID- 2898094 TI - Endocrine changes in Alzheimer's disease. AB - In conclusion, at present, no consistent endocrine abnormalities can be detected in patients suffering from Alzheimer's disease. However, assessment of neuroendocrine function might help identify subpopulations of patients with particular neurotransmission abnormalities who are likely to benefit from a specific pharmacologic strategy. For example, patients in whom cholinomimetic drugs produce the greatest elevation in plasma cortisol concentration appear to derive the most symptomatic benefit from these drugs. PMID- 2898095 TI - Prolactin and neuroleptic drugs. AB - Serum prolactin is reliably elevated by the antipsychotic drugs. Prolactin levels have been followed in psychotic patients during the use of these drugs as an indicator of underlying pathophysiology or as a reflection of drug activity. Considerable research is underway to elucidate further the potential clinical and research utility of the prolactin response to neuroleptic drugs. PMID- 2898096 TI - Effects of psychotropic medications on hypothalamic-pituitary-adrenal regulation. AB - The psychotropic medications reviewed in this paper have widespread clinical applicability in psychiatry and other branches of medicine. These drugs clearly can alter peripheral regulation of hypothalamic-pituitary-adrenal axis hormones. In general, psychotropic medications when administered acutely have a tendency to increase the output of both adrenal and pituitary hormones associated with the axis; the benzodiazepines appear to be the exception and indeed may decrease axis activity. Psychotropic agents may also alter the results of the dexamethasone suppression test as currently used in psychiatry, since they alter the neurotransmitters that regulate corticotropin-releasing hormone secretion and also because they may change the severity of the underlying pathophysiology. Withdrawal of these drugs after long-term administration may cause an elevation of these hormones, potentially increasing the false-positive rate of the dexamethasone suppression test and other neuroendocrine tests. PMID- 2898097 TI - Molecular cloning and analysis of the regulation of cys-14+, a structural gene of the sulfur regulatory circuit of Neurospora crassa. AB - The cys-14+ gene encodes sulfate permease II, which is primarily expressed in mycelia. cys-14+ is one of a set of sulfur-related structural genes under the control of cys-3+ and scon+, the regulatory genes of the sulfur control circuit. We have cloned cys-14+ from a cosmid library of Neurospora crassa DNA. A restriction fragment length polymorphism analysis showed that this clone maps to the region of chromosome IV corresponding to the cys-14+ locus. Northern blot analyses were used to examine the regulated expression of the cys-14+ gene. In the wild type, a 3-kilobase cys-14+ transcript was highly expressed under sulfur derepressing conditions but completely absent during sulfur repression. A cys-3 mutant, which cannot synthesize any of the sulfur-controlled enzymes, including sulfate permease II, did not possess any cys-14+ transcript under either condition. A cys-3 temperature-sensitive revertant completely lacked any cys-14+ mRNA at the conditional temperature but expressed the cys-14+ transcript upon derepression at the permissive temperature. Mutation of a second sulfur regulatory gene, scon(c), causes the expression of sulfur-related enzymes in a constitutive fashion; the scon(c) mutant showed a corresponding constitutive expression of cys-14+ mRNA, such that it was present even in cells subjected to sulfur repression conditions. These results show that the cys-14+ gene is regulated through the modulation of message content by the cys-3+ and scon(c) control genes in response to the sulfur levels of the cells. PMID- 2898099 TI - Synthesis of proteins in Escherichia coli immunoreactive with sera from individuals infected with human T-cell leukemia virus type I. AB - The env-pX IV fused gene of human T-cell leukemia virus type I (HTLV-I) was inserted into lac promoter-directed expression vectors for production of viral proteins in bacteria. Resulting recombinant plasmids, pK13 and pK15, directed synthesis of fused proteins of 59 kDa (Env-p40x) and 100 kDa (Gag-Env-p40x), respectively. Western blot analysis showed that these proteins were reactive with sera of patients with adult T-cell leukemia (ATL) and retained multiple antigenic determinants of viral proteins. In combination with recombinant Gag protein [S. Itamura, K. Shigesada, M. Imai, N. Kobayashi, T. Hamakado, T. Harada and M. Hatanaka, Gene 38, 57-64 (1985)], these bacterially synthesized proteins may provide a useful tool for differential diagnosis of ATL by detecting serum antibodies against individual viral proteins and for analysis of viral gene functions. PMID- 2898100 TI - [Delirium in the general hospital]. PMID- 2898098 TI - Double minute chromosomes can be produced from precursors derived from a chromosomal deletion. AB - Recent experiments have shown that gene amplification can be mediated by submicroscopic, autonomously replicating, circular extrachromosomal molecules. We refer to those molecules as episomes (S. Carroll, P. Gaudray, M. L. DeRose, J. F. Emery, J. L. Meinkoth, E. Nakkim, M. Subler, D. D. Von Hoff, and G. M. Wahl, Mol. Cell. Biol. 7:1740-1750, 1987). The experiments reported in this paper explore the way episomes are formed and their fate in the cell over time. The data reveal that in our system the episomes are initially 250 kilobases, but gradually enlarge until they become double minute chromosomes. In addition, we show that episomes or double minute chromosomes can integrate into chromosomes. Our results also suggest that episomes can be produced by deletion of the corresponding sequences from the chromosome. PMID- 2898101 TI - [Action of doubled derivatives of glutamic acid on mollusk neurons]. AB - Application of doubled derivatives of glutamic and evoked depolarization of the membrane of identified mollusk neurons, whereas glutamate elicited biphasic responses. The effect of these substances depended on the length of the chain (CH2)n between the residues of glutamic acid; it was maximal for n = 8. Changes in membrane conductance were shown to depend on the kind of stereo conformation of these residues. Hill's coefficient for tested compounds was about 0.75. It is suggested that the doubled derivatives of glutamic acid are agonists of glutamate D-receptors. PMID- 2898102 TI - [Action of mediators on pyramidal and nonpyramidal neurons in slices of the guinea pig hippocampus]. AB - Effects of acetylcholine (Ach), norepinephrine (NE), 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) on the background activity were tested in the field CA3 in the guinea pig hippocampal slices. Three groups of neurons were investigated: nonpyramidal neurons of stratum radiatum-moleculare (NSR), neurons with single spike discharges of stratum pyramidale (SD-units) and neurons with complex spike discharges (CD-units) in the same stratum. Effects of Ach and NE were tested also on presumed interneurons of str. oriens-pyramidale (ISP). Similarity between NSR, ISP and SD units and their difference from CD units may be suggested on the basis of the drugs action. Activity of the CD units was suppressed by NE, 5-HT and GABA, while in a half of these cells Ach evoked inhibitory-activatory succession of effects. On the contrary, NSR, ISP and SD units were monophasically activated by NE and Ach. Though 5-HT and GABA suppressed the activity in some of NSR and SD units, many of them were activated. Excitatory influence of Ach, NE and 5-HT on NSR was preserved with the blockade of synaptic transmission, which suggests direct influence of the drugs on the investigated cells. PMID- 2898104 TI - International symposium on Alzheimer's disease. PMID- 2898103 TI - The neurobiology of aging: does it predispose to depression? AB - This review examines the various research approaches undertaken to investigate possible central nervous system correlates of major depressive illness and relates findings from these studies to the alterations in central nervous system and neuroendocrine function that normally accompany aging in humans. The topics reviewed include: epidemiology of depression and suicide in the elderly; monoamine theories of depression; neuroendocrine disturbances in depression; and imaging studies. PMID- 2898105 TI - Brain neurotransmitters and eating behavior in the elderly. AB - Based on published evidence, it is reasonable to propose that disturbances in brain neurotransmitters may contribute to the development of eating disorders in the elderly. The precise nature of these disturbances, however, cannot be defined until further studies are performed in aged animals and more careful attention is given to the specific brain site involved and the exact nature of the neurochemical change. PMID- 2898106 TI - Other likely BBB functions possibly related to aging. AB - In addition to selectively facilitating transport between blood and brain, the BBB appears to carry out other functions. It probably protects the brain from trophic peptides in blood. It also maintains a different electrolyte concentration in the neuronal environment relative to blood plasma. It also prevents the loss of locally produced neurotransmitters and modulator substances in brain. The cytoplasmic enzymes in brain capillary endothelial cells may also alter molecular structure on route between blood and brain. Any of these functions may be disturbed in the aging brain, but we do not understand them well enough to draw any conclusions as yet. PMID- 2898107 TI - Anorexia in the elderly. AB - Weight loss and anorexia occur commonly in the elderly. While in many cases the anorexia can be attributed to associated disease processes, it does appear that a true anorexia of aging exists. Animal studies have suggested that older rodents have an excessive satiety effect of cholecystokinin and a decreased opioid feeding drive. Other older persons develop anorexia in association with depression. In these subjects, excess corticotropin-releasing factor may be the neurotransmitter involved in the pathogenesis of the anorexia. In Alzheimer's disease, decreases in norepinephrine and neuropeptide Y may be involved in the anorexia seen in the these patients. PMID- 2898108 TI - In vivo analysis of cortical amino acid neurotransmitters collected in the rat by a new double lumen push-pull catheter system. AB - The release of both endogenous and newly synthesized amino acid neurotransmitters was examined simultaneously in different areas of the cerebral cortex in the freely moving rat. An array of push-pull guide tubes was implanted permanently to rest above the frontal, parietal, temporal and occipital areas of the cortex of each rat. Then a new double-lumen catheter system, specially adapted for localized push-pull perfusion of the conscious animal, was used to perfuse an artificial cerebrospinal fluid at each cortical site. For the new synthesis experiments, 0.5 microCi of [14C]glucose in a volume of 2.0 microliter was first microinjected into the perfusion site as a precursor to label amino acids. After the site was perfused at a rate of 12.0 microliter/min, each of the samples was assayed by two-dimensional thin-layer chromatography. In a second analysis, the content of six endogenous amino acids present in unlabeled samples of push-pull perfusate was quantified by high-performance liquid chromatography analysis with electrochemical detection. The results showed a notable homogeneity among each of the four cortical areas in the content of four of the six amino acids examined. Endogenous glutamine exhibited the highest proportional content in the cortical perfusates, whereas glutamic acid was proportionally higher in terms of new synthesis. An anatomical analysis revealed that the level of endogenous glutamic acid in the frontal area was significantly lower than that found in the occipital or temporal regions of the rat's cortex. An opposite result was obtained when the proportional synthesis of glutamic acid from [14C] glucose was compared in different cortical regions in that a statistically higher release occurred in the frontal than in the occipital cortex. PMID- 2898110 TI - [125I]dynorphin(1-8) produces a similar pattern of kappa-opioid receptor labelling to [3H]dynorphin(1-8) and [3H]etorphine in guinea pig brain: a quantitative autoradiographic study. AB - kappa-Opioid receptors were radiolabelled with the peptides [125I]dynorphin(1-8) and [3H]dynorphin(1-8) or with [3H]etorphine on guinea pig forebrain and cerebellar sections and visualized by quantitative autoradiography. All three radioligands yielded similar patterns of kappa-receptor localization. However, quantitative analysis showed that using saturating concentrations of the tritiated radioligands the apparent density of specific [3H]etorphine-labelled kappa-sites was 1.5-5.4 times greater than that achieved with [3H]dynorphin(-8). The apparent rank order of regional density of kappa-sites on a quantitative basis with all 3 radioligands was similar. A high density of kappa-receptors was found in the nucleus accumbens, striatum, globus pallidus, cerebral cortex (layers V-VI), hippocampal and cerebellar molecular layers, substantia nigra and substantia gelatinosa of the spinal cord. A lower density of these sites was associated with the thalamus, hypothalamus and the amygdaloid complex. Thus, in view of the advantages of using iodinated ligands in autoradiography this study has shown that [125I]dynorphin(1-8) is an acceptable ligand for labelling kappa receptors in the brain. PMID- 2898109 TI - Striatal grafts in rats with unilateral neostriatal lesions--I. Ultrastructural evidence of afferent synaptic inputs from the host nigrostriatal pathway. AB - Tyrosine hydroxylase immunocytochemistry, in combination with Golgi impregnation, has been used to study the dopaminergic afferent input to striatal suspension grafts implanted into the previously ibotenic acid-lesioned striatum in adult recipient rats. The rats were perfused for combined light- and electron microscopy at 10-11 months after transplantation, at the end of a series of behavioural experiments and a study of in vivo GABA release, reported in the two accompanying papers. A tyrosine hydroxylase-positive fibre network occurred within the grafts in all eight specimens analysed. The tyrosine hydroxylase positive fibres had a distinct "patchy" distribution, throughout the graft tissue, and within these patches the terminal density was similar to that of the normal intact striatum. Ultrastructurally, the tyrosine hydroxylase-positive fibres were seen to make abundant synaptic contacts with neuronal elements within the grafts. As in the normal striatum, they were all of the symmetric type and dendritic shafts and spines were the most usual postsynaptic targets. Sections from three of the grafted animals were taken for combined Golgi-impregnation and immunostaining. Only cells of the medium-sized densely spiny type were impregnated in this material. Six of them, which had portions extending into the immunostained neuropil, were drawn using a camera lucida and processed for electron microscopy. Tyrosine hydroxylase-positive boutons were seen to make symmetrical synaptic contacts onto the shafts and spines of the impregnated dendrites, and in one case also with the perikaryon. The results indicate that the medium-sized densely spiny neuron type (which is a predominant target for the dopaminergic afferents in the normal striatum) is abundant in the grafted tissue, and that these neurons represent a synaptic target also for the tyrosine hydroxylase-positive innervation of the striatal grafts. PMID- 2898111 TI - Bradykinin-induced accumulation of [3H]inositol-1-phosphate in human embryonic pituitary tumour cells by activation of a B2-receptor. AB - Agonist-induced accumulation of [3H]inositol-1-phosphate ([3H]IP1) was studied using human embryonic pituitary tumour cells (Flow 9000). Stimulation of Flow 9000 cells, prelabelled with [3H]inositol, with the nonapeptide bradykinin (BK), or its analogues and fragments produced a differential accumulation of [3H]IP1. BK-related peptides exhibited the following rank order of potency in this assay: BK = [Lys]BK greater than [Met-Lys]Bk much greater than [Des-Arg9]BK much greater than BK(1-6) = BK(2-7) = BK(2-9). BK and [Lys]BK produced half-maximal effects at 2-3 nM. [3H]BK receptor binding studies showed that BK and [Des-Arg9]BK produced a concentration-dependent inhibition of [3H]BK binding with Ki values of 4.8 +/- 1.9 nM (n = 3) and 6.8 +/- 0.7 microM (n = 3) respectively. These studies suggest the presence of B2-bradykinin receptors on the human embryonic pituitary tumour cell-line which appear to be coupled to the phosphatidyl inositol turnover signal transduction mechanism. Cholecystokinin, angiotensin II, vasopressin, thyrotropin releasing hormone and bombesin also stimulated [3H]IP1 production but were generally much weaker than BK. In contrast, substance P, eledoisin, somatostatin, neurotensin, VIP, NPY, CGRP, U50488, DAGO and DADLE appeared inactive in this system at 10 microM. PMID- 2898112 TI - An endogenous substance of the brain, tetrahydroisoquinoline, produces parkinsonism in primates with decreased dopamine, tyrosine hydroxylase and biopterin in the nigrostriatal regions. AB - An endogenous substance of the human brain, tetrahydroisoquinoline (TIQ), that had been increased in the parkinsonian brain, produced parkinsonism in marmosets after daily injection of TIQ (50 mg/kg per day, s.c. for 11 days). Tyrosine hydroxylase activity, total biopterin and dopamine concentrations were also decreased in TIQ-treated marmosets. The results suggest that TIQ is one of the candidates of neurotoxins to produce parkinsonism. PMID- 2898113 TI - Effects of D-(-)-aminophosphonovalerate on behavioral and histological changes induced by systemic kainic acid. AB - In rats, the seizures induced by systemic kainic acid (KA) are followed by extensive neuronal damage, notably in the hippocampal region. We report that the specific N-methyl-D-aspartate (NMDA) receptor antagonist, D-(-) aminophosphonovalerate (D(-)APV), given i.c.v. prior to or 2 h after i.p. KA injection markedly protected CA1 but not other hippocampal neurons against degeneration. In contrast, D(-)APV had no effect on KA-induced wet dog shakes or on behavioral seizures. We conclude that NMDA receptors participate in the neurotoxic but not in the behavioral effects of systemic KA. PMID- 2898114 TI - Evidence of N-methyl-D-aspartate receptor-mediated modulation of the aortic baroreceptor reflex in the rat nucleus tractus solitarii. AB - Microinjections of N-methyl-D-aspartate (NMDA) into the medial area of the nucleus tractus solitarii (NTS) of the rat led to a decrease in arterial pressure and heart rate. The NMDA receptor antagonist 2-amino-5-phosphonovalerate (AP5) reduced the cardiovascular responses to NMDA. Depressor and bradycardic responses to aortic nerve stimulation were reduced by AP5 but not by a substance P antagonist, injected into the NTS. High K+ stimulation caused a calcium-dependent release of glutamate and aspartate from tissues in the area of the NTS. These results provide evidence of NMDA receptor-mediated modulation of the aortic baroreceptor reflex in the rat NTS. PMID- 2898115 TI - NMDA- and kainate-evoked GABA release from striatal neurones differentiated in primary culture: differential blocking by phencyclidine. AB - N-Methyl-D-aspartate (NMDA) stimulated (EC50 = 19.4 +/- 1.9 microM) gamma aminobutyric acid (GABA) release from highly purified striatal neurones differentiated in primary culture. NMDA effect was inhibited (i) in a competitive manner by DL-2-amino-5-phosphonovalerate (APV) and (ii) in a non-competitive manner by phencyclidine (PCP). Kainate (KA) also stimulated GABA release, but this effect was never inhibited by PCP despite the multiple conditions tested (KA stimulation performed, after or not NMDA application, in the presence or not of NMDA). The existence of two distinct receptor-channel complexes on striatal neurones selectively activated by NMDA and KA is discussed. PMID- 2898116 TI - Glutamate and dopamine modulate synaptic plasticity in horizontal cell dendrites of fish retina. AB - Horizontal cell dendrites protruding into the cone pedicles in fish retina exhibit a light-dependent plasticity. In a light-adapted retina they form numerous spinules having membrane densities at their tips. These spinules disappear during dark adaptation. Experiments with light- or dark-adapted retinas which were incubated in glutamate or its agonists and antagonists, respectively, revealed that this putative cone transmitter is able to reduce the expression of spinules in a light-adapted retina. Dopamine, on the other hand, induces the formation of spinules in a dark-adapted retina and haloperidol reduces the expression in a light-adapted retina. These data suggest a control of spinules plasticity through two retinal neurotransmitter systems. PMID- 2898117 TI - Pharmacological characterization of D1 and D2 dopamine receptors in rat limbocortical areas. I. Frontal cortex. AB - The mesolimbocortical dopaminergic system innervates several brain regions including the frontal cortex. The aim of our work was both to identify and to pharmacologically characterize the dopamine receptors located in this brain area. We found that different selective agonists for D1 receptors were able to increase adenylate cyclase activity, and these effects were antagonized by haloperidol and SCH 23390. Moreover different agonists for D2 receptors inhibited the cyclic AMP generating system, and these effects were prevented by (-)-sulpiride. According to the paradigm that D1 receptors are linked with adenylate cyclase in a stimulatory way, while D2 receptors are linked with the same enzyme in an inhibitory way, our results indicate the presence of both D1 and D2 receptors in rat frontal cortex. PMID- 2898118 TI - Pharmacological characterization of D1 and D2 dopamine receptors in rat limbocortical areas. II. Dorsal hippocampus. AB - The mesolimbocortical dopamine (DA) system innervates several brain regions including the hippocampus. The aim of the present study was both to identify and to pharmacologically characterize the DA receptors located in this brain area. The results show that different agonists for D1 DA receptors, such as DA itself, SKF82526 and (-)-apomorphine, were able to increase adenylate cyclase activity, and these effects were antagonized by haloperidol and SCH 23390. Moreover bromocriptine, lisuride and RU 24213, which are agonists for D2DA receptors, inhibited the cyclic AMP generating system and these effects were prevented by ( )-sulpiride. According to the paradigm that D1 DA receptors are linked with adenylate cyclase in a stimulatory way, while D2 DA receptors are linked with the same enzyme in an inhibitory way, our results indicate the presence of both D1 and D2 receptors in rat hippocampus. Localization studies show that both DA receptor subtypes are restricted to the dorsal part of the hippocampus. PMID- 2898120 TI - Drug induced disease as a cause of admission to a country hospital. AB - During 1983, 15% of admissions to the medical ward of Kaitaia Hospital resulted from ill effects of prescribed medication. Tranquillisers, digoxin, beta blockers, other hypotensive drugs, and nonsteroid antiinflammatory drugs were the offending agents in 73% of these admissions. Drug induced illness makes an important contribution to the work-load of a general medical ward, and more care in the prescription of these classes of drugs might substantially reduce this contribution. PMID- 2898121 TI - Beta-2 agonists and asthma morbidity. PMID- 2898119 TI - A quantitative assessment by flow cytometry of the preservation of the Thy-1 antigen by various fixation procedures. AB - A quantitative assessment of the effects of various fixatives upon the preservation of the Thy-1 surface antigen has been undertaken. A panel of 5 monoclonal antibodies (MAbs) have been reacted with mouse lymphocytes treated with various fixatives, and their binding analysed by flow cytometry using a fluorescence activated cell sorter. It was found that 2% paraformaldehyde (PFA) provided the best antigenic preservation, as detected by both the anti Thy-1.1 and anti Thy-1.2 MAbs. The effectiveness of 2% PFA fixation is further demonstrated by the immunohistochemical identification of the Thy-1 antigen in sections of mouse cerebellar cortex. PMID- 2898122 TI - Benzodiazepine addiction. PMID- 2898123 TI - The prescribing of psychoanxiolytic and analgesic drugs. PMID- 2898124 TI - Cerebrospinal fluid activity of dynorphin-converting enzyme at term pregnancy. AB - Cerebrospinal fluid activity of a dynorphin-converting enzyme transforming prodynorphin-derived peptides to [Leu]enkephalin-Arg6 was measured in 12 women at term pregnancy before cesarean section and in eight nonpregnant, nonpuerperal controls. In pregnant women, the dynorphin-converting enzyme activity was significantly lower (mean +/- SD 6.8 +/- 3.8 U/L) than in nonpregnant controls (11.7 +/- 2.6 U/L; P less than .01). Furthermore, prodynorphin-derived [Leu]enkephalin-Arg6-containing polypeptides were significantly increased in samples from pregnant women (P less than .05). This indicates that a reduced activity of opioid peptide-degrading enzymes might contribute to an increased resistance to pain at term pregnancy. PMID- 2898125 TI - Presence of carcinogenic glutamic-acid pyrolysis products in human cataractous lens. AB - The carcinogenic glutamic-acid pyrolysis products, 2-amino-6-methyldipyrido[1,2 a:3',2'-d]imidazole (Glu-P-1) and 2-amino-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P 2), were found to be present in human cataractous lenses, but not in normal bovine lenses. Contents of Glu-P-1 and Glu-P-2 in 35 human cataractous lenses were 832 and 20 ng, respectively. These results indicate that the human cataractous lens is exposed to the fluorescent compounds, carcinogenic glutamic pyrolysis products. PMID- 2898126 TI - The antinociceptive role of a bulbospinal serotonergic pathway in the rat brain. AB - The antinociceptive role of spinal serotonin (5-HT) neurons descending from 5-HT cells near the ventrolateral surface of the medulla oblongata was investigated by stimulating these cells in normal rats, in rats with generalized or selective chemical ablation of 5-HT nerves, and in rats with postsynaptic blockade of 5-HT receptors. Electrical stimulation of the lateral medulla elicited analgesia in normal rats; the increase in pain threshold was proportional to the intensity and to the frequency of stimulation. In addition, microinjection of kainic acid or L glutamate at the same sites also produced analgesia. However, generalized destruction of CNS 5-HT nerves produced by intraventricular injection of 5,7 dihydroxytryptamine (5,7-DHT) or selective destruction of spinal 5-HT nerves produced by intraspinal injection of 5,7-DHT reduced the magnitude of the antinociceptive responses to electrical stimulation. Postsynaptic blockade of CNS 5-HT receptors produced by intraventricular injection of cyproheptadine also reduced the stimulation-produced analgesia. The specificity of the lesions for 5 HT nerves is demonstrated by the lack of effect on the levels of noradrenaline in the same brain regions. The results indicate that the activity of 5-HT nerve cells adjacent to the ventrolateral surface of the medulla oblongata and projecting to the spinal cord serves to elevate pain threshold. PMID- 2898128 TI - A HindIII RFLP demonstrated for the kit oncogene on chromosome 4. PMID- 2898127 TI - Human tyrosine hydroxylase and insulin genes are contiguous on chromosome 11. AB - The gene for the catecholamine biosynthetic enzyme, tyrosine hydroxylase (TH), has been previously mapped to human chromosome 11 p15.5 in the vicinity of the loci for insulin (INS) and for the oncogene Harvey Ras 1 (HRAS). Here we show that gene probes derived from recombinant clones containing either human TH or INS cross-hybridize with each other. Direct DNA sequencing demonstrates that these genes are physically linked on chromosome 11. The TH gene is 5' to INS and is separated by only 2.7 kb of flanking DNA. Both genes have the same transcriptional polarity and form a head-to-tail linkage group with insulin-like growth factor 2 (IGF-2) in the order: 5' - TH - INS - IGF-2 - 3'. Because of the close physical proximity of these genes, previously described polymorphisms for INS are identical to those observed with TH. The localization of TH to the highly polymorphic INS locus provides four new restriction fragment length polymorphisms which should help determine rapidly whether defects in TH are responsible for bipolar affective disorder in the Old Order Amish and other populations. PMID- 2898129 TI - Isolation and mapping of a polymorphic DNA sequence (pJCZ30) on chromosome 6 [D6S37]. PMID- 2898130 TI - Isolation and mapping of a polymorphic DNA sequence (pTHH26) on chromosome 11 [D11S149]. PMID- 2898131 TI - Isolation and mapping of a polymorphic DNA sequence (pEFD70.3) on chromosome 18 [D18S23]. PMID- 2898132 TI - Drug-induced psychosis and depression in the elderly. AB - This article discusses drug-induced psychosis and depression in the elderly population. Selected reports with particular emphasis on the geriatric population are evaluated with histamine blockers, antiparkinson, anti-inflammatory, antituberculosis, antineoplastic, antidepressant, anticonvulsant, cardiac, antihypertensive, and steroid drugs. Particular emphasis is placed on possible mechanisms of these side effects and factors contributing to increased incidence in the elderly population. In review, the clinician is advised to use special caution when prescribing these agents in the elderly considering increasing patterns of drug-induced psychosis and depression. PMID- 2898133 TI - Neuroleptics and alternative treatments. Management of behavioral symptoms and psychosis in Alzheimer's disease and related conditions. AB - Behavioral problems, and even psychotic symptoms, are universally acknowledged as among the most distressing consequences of dementia. A majority of patients experience either or both at some time during the course of dementia. Agitation is so common that accurate prevalence rates are difficult to ascertain; the available data suggest approximately 70 to 80 per cent of patients manifest this behavior in some form. Psychotic symptoms in some form occur less frequently, but perhaps affect up to half of demented patients at some time. Neuroleptic medications are among the psychoactive drugs most frequently prescribed for the demented elderly, yet they carry the risk of considerable morbidity from side effects, both acute (extrapyramidal syndromes, cardiovascular toxicity, anticholinergic effects) and chronic (tardive dyskinesia). They are most widely used for behavioral and psychotic symptoms; however, their efficacy for these problems is far from unequivocally established. The multiple medical problems of the elderly add to the complexity of diagnosing and managing these symptoms. Systematic delineation of the etiology, course, and prognosis of behavioral and psychotic symptoms may clarify the indications for such treatment. Further research on effective adjuncts and alternatives to neuroleptic treatment in the demented elderly may facilitate patient management, maximizing efficacy and reducing potential adverse consequences. PMID- 2898134 TI - Antidepressant drug studies in the elderly. AB - This article reviews the literature on antidepressant drug trials conducted in elderly populations. Only 27 studies of cyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and psychostimulants deal specifically with subjects that were over age 60. Methodologic problems were found in many studies, including lack of diagnostic criteria and inadequate controlling for cognitive impairment, concurrent medical illnesses, and nonpsychotropic medications. Most studies compared second-generation antidepressants against placebo or tricyclic antidepressants (TCAs). Antidepressant drugs are effective treatments for geriatric depression, and limiting side effects are comparable with those seen in younger populations. PMID- 2898135 TI - Psychotropic drug interactions in the patient with late-onset psychosis and mood disorder. Part 1. AB - We have discussed major drug interactions involving neuroleptics and MAOIs. Interactions in the older patients are probably more frequent owing to the larger number of medications used. When interactions do occur in the elderly, the effects may be more severe and of a longer duration than those seen in younger patients. Many (but not all) drug-drug interactions are predictable, given a basic knowledge of the pharmacologic effects of the agents in question. In a number of cases, there are therapeutic alternatives to agents that have been reported to interact with psychotropic medications. The clinician should consider the likelihood of adverse drug interactions to be a significant concern as the age of the patient and the number of concurrently administered medications increase. PMID- 2898136 TI - Psychotropic drug interactions in the patient with late-onset depression or psychosis. Part 2. AB - We now conclude our discussion of psychotropic drug interactions in the late-life depression or psychosis patient. We have attempted to point out the more common drug interactions, while also mentioning less well-reported, yet potentially important interactions. The outcome of such adverse reactions as we have described herein is usually of greater concern in older patients. Accordingly, this population would benefit considerably from accurate reporting of any suspected drug interactions. Although most drug interactions are usually somewhat predictable, it is very important that those interactions that are not expected otherwise be well documented. As stated elsewhere in this review, a good basic knowledge of the pharmacology of the agents in question will serve the clinician and his or her patient well. PMID- 2898137 TI - Association of psychosis and movement disorders in the elderly. AB - There are a number of different relationships among aging, psychosis and movement disorders, most of which have been proposed to involve the neurotransmitter dopamine. Dopamine content and dopamine receptors have been shown to decrease with age, which may relate to the time of onset of different motor and psychotic disorders, as well as to the appearance of these disorders. For example, some so called senile movement disorders, such as senile tremor and senile chorea, may relate to alterations in dopaminergic transmission with age, as might the general findings of increased slowing of movements and mildly increased rigidity with age, although it is not clear how common some of these changes are in the medically healthy elderly. Decrease in dopamine with age may also be associated with the findings that choreiform and psychotic disorders (which have been proposed to be related to excess dopaminergic activity) tend to predominate at younger ages, whereas parkinsonism is more common at later ages. Certain findings support this notion, such as the appearance of both dyskinesia and psychosis in patients treated with L-dopa, the finding that psychosis may be less common in patients with later-onset Huntington's disease, and the fact that neuroleptic induced parkinsonism is often more severe in the elderly. However, the situation is more complicated than this, because there are a number of phenomena that do not fit the pattern, including the observation of an increased incidence of tardive dyskinesia in the elderly. Age-related changes in other transmitters are undoubtedly important in both movements disorders and psychosis, and even dopamine has been proposed to have both trophic and toxic properties over the aging process. In general, care is warranted in the use of any psychotropic medications in the elderly, because there can be widespread and often unpredictable effects of these drugs on both motor and mental function. PMID- 2898138 TI - [The use of DNA recombination technics in human genetics]. PMID- 2898139 TI - Egg yolk paste for determining some food poisoning bacteria. AB - Egg yolk, aseptically prepared from fresh eggs, was partially dehydrated with a 40% high fructose corn syrup solution, and 10% salt was added. This salted yolk paste was added to mannitol salt agar for the detection of Staphylococcus aureus, to NaCl-glycine Kim and Goepfert medium for detection of Bacillus cereus, to Clostridium welchii agar for detection of C. perfringens, and to Gifu anaerobic medium for detection of C. botulinum. These food poisoning bacteria showed the same lecithovitellin (LV) reaction on these media as on the same media prepared with fresh egg yolk. The yolk paste could be stored at -20 C without freezing and did not show any bacterial growth after holding at 25 C for 30 days. The increased salt content resulted from the addition of salted yolk paste to the media did not inhibit the growth of the food poisoning bacteria used in these experiments. For the identification of the food poisoning bacteria used in this work, and which give a LV reaction, salted yolk paste is more convenient to use than yolk separated from fresh shell eggs. PMID- 2898140 TI - [Zona as a predictive element of the infection by human immunodeficiency type 1 virus in Bangui (Central African Republic)]. PMID- 2898141 TI - A histone H1 protein in sea urchins is encoded by a poly(A)+ mRNA. AB - Typical histone genes lack intervening sequences and encode small mRNAs (400-800 nucleotides) with short leader and trailer regions. Most histone mRNAs are not polyadenylylated but rather terminate in a highly conserved stem and loop structure. The early, late, and testis-specific histone genes of sea urchins, described to date, have this typical histone gene structure. We have identified an unusual H1 gene, H1-delta, in sea urchins that encodes a poly(A)+ mRNA. This mRNA is one of a group of polyadenylylated transcripts homologous with H1 gene probes. The sequence of H1-delta had been determined. H1-delta encodes a different H1 protein. Although the temporal expression of H1-delta mRNA is similar to that of other late H1 (beta and gamma) mRNAs, its spatial distribution at the time of maximal accumulation is distinct and confirms that H1-delta is regulated differently than other H1 genes. PMID- 2898142 TI - Structural analysis of the 5' flanking region of the beta-globin gene in African sickle cell anemia patients: further evidence for three origins of the sickle cell mutation in Africa. AB - Haplotype analysis of the beta-globin gene cluster shows two regions of DNA characterized by nonrandom association of restriction site polymorphisms. These regions are separated by a variable segment containing the repeated sequences (ATTTT)n and (AT)xTy, which might be involved in recombinational events. Studies of haplotypes linked to the sickle cell gene in Africa provide strong argument for three origins of the mutation: Benin, Senegal, and the Central African Republic. Nevertheless, the haplotype determination does not give any information about the variable segment and does not totally exclude the possibility of recombination leading to different haplotypes linked to the mutation. The structure of the variable segment in the three African populations was studied by S1 nuclease mapping of genomic DNA, which allows a comparison of several samples. A 1080-base-pair DNA segment was sequenced for one sample from each population. S1 nuclease mapping confirmed the homogeneity of each population with regard to both (ATTTT)n and (AT)xTy repeats. We found three additional structures for (AT)xTy correlating with the geographic origin of the patients. Ten other nucleotide positions, 5' and 3' to the (AT)xTy copies, were found to be variable when compared to homologous sequences from human and monkey DNAs. These results allow us to propose an evolutionary scheme for the polymorphisms in the 5' flanking region of the beta-globin gene. The results strongly support the hypothesis of three origins for the sickle mutation in Africa. PMID- 2898143 TI - A retrovirus carrying an MDR1 cDNA confers multidrug resistance and polarized expression of P-glycoprotein in MDCK cells. AB - A full-length cDNA for the human multidrug resistance gene 1 (MDR1) has been inserted into a retroviral vector containing a murine Harvey sarcoma virus from which the viral oncogene was deleted. Ecotropic and amphotropic virus was produced after transfection of this vector into psi-2 and PA-12 packaging cell lines. This virus conferred the full phenotype of multidrug resistance on mouse and human cell lines. Viral titers of up to 2 X 10(5) drug-resistant colonies per ml were observed. Infected cells became resistant to colchicine, vinblastine, doxorubicin, VP16 (etoposide), and puromycin, but not cisplatin, indicating that the presence of the human MDR1 gene is sufficient to cause multidrug resistance. When the dog kidney cell line MDCK was infected with the MDR1 virus, P glycoprotein was expressed in a polarized manner on the upper surface of the cells, showing that the cloned cDNA also encodes information for polarized expression of P-glycoprotein. The MDR1 virus should be useful for introducing this drug resistance gene into a variety of cell types for biological experiments in vitro and in vivo. PMID- 2898144 TI - Rapid desensitization of glutamate receptors in vertebrate central neurons. AB - We have examined glutamate receptor desensitization in voltage-clamped embryonic chicken spinal cord neurons and postnatal rat hippocampal neurons maintained in culture. Rapid currents that rose in 0.8-3.6 msec were evoked when glutamate was ionophoresed with 0.5- to 1.0-msec pulses. With prolonged pulses or brief, repetitive pulses, glutamate-evoked currents decayed rapidly in a manner that was independent of holding potential. A similar desensitization occurred following close-range pressure ejection of glutamate. The rapid, desensitizing glutamate current exhibited a linear current-voltage relation and it was not blocked by 2 amino-5-phosphonovalerate, suggesting that it was mediated by N-methyl-D aspartate-insensitive (G2) receptors. Desensitization of G2 receptors may be agonist-dependent: currents evoked by kainate, a selective G2 agonist, did not decay, whereas prior application of glutamate did reduce the size of kainate responses. The appearance of the rapid current depended critically on the position of the ionophoretic pipette. Such glutamate-receptor "hot spots" often corresponded to points of contact with neighboring neurites, which raises the possibility that they are located at synapses. PMID- 2898145 TI - Development of stimulus selectivity and functional organization in the suprasylvian visual cortex of the cat. AB - We have recorded from single neurons in the medial bank of the middle suprasylvian sulcus (PMLS) of anaesthetized and paralysed cats aged between nine days and eight weeks. Visual responses were assessed qualitatively, by using conventional projected stimuli, and quantitatively for drifting, high-contrast gratings of optimum spatial and temporal frequencies, but varying in orientation and direction of drift. At 9 days of age, some cells in the PMLS were spontaneously active but in three long penetrations only one visually responsive neuron was isolated. Between 9 and 15 days there was a rapid increase in the proportion of responsive units, which first appeared in small clusters in the lower layers (IV, V, VI). During the second and third postnatal weeks, spontaneous activity and the strength of visual responses increased to adult levels, and the proportion of cells showing rapid habituation to visual stimulation decreased. Even before two weeks of age, at least 85% of responsive cells in the PMLS were selective, by quantitative criteria, for image motion along one particular axis, and a majority of these were clearly direction selective (responding to movement in one direction significantly more strongly than to that in the opposite). By the end of the third postnatal week the proportion of units with strong direction preference reached adult levels. The selective cells were initially more broadly 'tuned', on average, for the direction of motion of a grating (mean half-width in animals of 10-12 days was 32.6 degrees), but the sharpness of tuning improved to reach the adult level (ca. 23 degrees) during the third postnatal week. In animals younger than three weeks a slightly smaller proportion of cells than in adults (but always more than one third of all visually responsive cells) responded to stationary, contrast modulated gratings. The majority of these cells showed clear selectivity for the orientation of a flashed grating. A few 'non-selective' cells were found in the youngest animals but by the end of the third postnatal week virtually all cells responsive to stationary gratings displayed orientation selectivity. There was always good agreement between the preferred orientations for stationary and drifting gratings. Even before two weeks of age, when responsive cells occurred only in small clusters, there was a clear tendency for neighbouring neurons to have similar or opposite preferred directions, just as in adult cats. By 2-3 weeks of age there were clear progressive shifts in stimulus preference along oblique or tangential tracks.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2898146 TI - Analysis of the rat liver gap junction protein: clarification of anomalies in its molecular size. AB - The major gap junction polypeptide in most tissues has an apparent molecular mass of 27 kDa with a 47 kDa dimer present in junction-enriched fractions. However, a 54 kDa protein recognized by gap junction-specific antibodies has been reported and a complementary DNA (cDNA) sequence for both human and rat liver gap junctions codes for a 32 kDa protein. In this paper we show that these are all forms of the same gap junction protein that can be observed on SDS-polyacrylamide gels simply by varying the concentration of acrylamide in the gels. A 64 kDa dimer is also obtainable. Antibodies to the gap junction protein or to a synthetic peptide constructed to match the rat liver gap junction amino-terminal sequence recognize all of these forms. Under some conditions a 54 kDa dimer is 'preferred', explaining the presence of this species in whole tissue homogenate Western blots. These results clarify several controversies and indicate that the protein forming the gap junction channel probably undergoes no major post translational modification as the cDNA sequence codes for a protein of molecular mass 32 kDa and this protein species and its 64 kDa dimer are demonstrable on SDS polyacrylamide gels under appropriate conditions. PMID- 2898147 TI - Responses to GABA, glycine and beta-alanine induced in Xenopus oocytes by messenger RNA from chick and rat brain. AB - Poly (A)+ messenger RNA (mRNA) was extracted from rat and chick brains, and injected into oocytes of Xenopus laevis. This led to the expression of receptors that evoked membrane currents in response to gamma-aminobutyric acid (GABA), glycine and beta-alanine. These currents all inverted at about the chloride equilibrium potential in the oocyte, and showed a marked rectification at negative potentials. Oocytes injected with mRNA from chick optic lobe gave large responses to GABA and beta-alanine, but small responses to glycine. In contrast, one fraction of mRNA from rat cerebral cortex (obtained by sucrose density gradient centrifugation) caused oocytes to develop sensitivity to GABA, glycine and beta-alanine, but very little to GABA. The pharmacological properties of the three amino acid responses also differed. Barbiturate and benzodiazepines potentiated the responses to GABA and beta-alanine, but not to glycine. Strychnine reduced the responses to glycine and beta-alanine, but not to GABA, whereas bicuculline reduced the responses to GABA and beta-alanine, but not to glycine. We conclude that different species of mRNA code for receptors to GABA and glycine, and possibly also for separate beta-alanine receptors. PMID- 2898148 TI - The distribution of the incubation period for the acquired immunodeficiency syndrome (AIDS). AB - This paper contains details of methods and full results of estimates of the incubation period of acquired immunodeficiency syndrome (AIDS) that were outlined in a previous paper by Medley et al. (Nature, Lond. 328, 719 (1987)). The original model is modified to assess the influence of age and sex on the incubation period: age, but not sex, is statistically significant. The difficulties associated with interpretation of these data, and the additional information that would be required to resolve these difficulties are discussed. PMID- 2898149 TI - Effect of amino acids on renal tubular bicarbonate reabsorption by the rat kidney. AB - This study shows that L-arginine, a dibasic amino acid, which decreases in proximal convoluted tubule HCO3 transport, does not inhibit renal Na+/K+ ATPase activity or O2 consumption in vitro. Thus, a mechanism(s) other than inhibition of Na+/K ATPase likely accounts for the inhibitory effect of dibasic aminoacids on HCO3 transport in the superficial proximal convoluted tubule. Neutral and acid aminoacids, unlike dibasic aminoacids, do not inhibit HCO3 transport in this nephron segment. PMID- 2898151 TI - Factors which modify neural control of the airway. PMID- 2898150 TI - Rheogenic transport of basic and acidic amino acids across the brush border of Necturus small intestine. AB - In studies with isolated Necturus intestine, glutamate (Glu-) and Na+ each enhanced the mucosal influx of the other. Measurement of apical membrane potential, Va, with microelectrodes revealed a rapid depolarization with addition of 10 mM mucosal Glu-. This depolarization was Na+ dependent. Upon complete removal of Cl- from the bathing medium Va hyperpolarized and the Glu- -induced depolarization increased significantly. However, removal of Cl- did not alter the total Glu- influx. These data suggest that external Cl- attenuates the rheogenicity of Na+/Glu- cotransport in the apical membrane of the absorptive cells. We have presented a model consistent with these observations in which Cl- competes with one -COO- group of Glu- for its binding site on the carrier. The two complexes which may form, carrier/Glu-/2Na+ or carrier/Glu-/2Na+/Cl-, allow for either electrogenic or electroneutral transport of Glu-, depending on the ratio [Glu-]/[Cl-] in the extracellular fluid. In other experiments, addition of mucosal L-lysine (Lys+) induced a rapid depolarization of Va. In the presence of Na+, the depolarization appeared to be saturable with respect to Lys+ concentration. In Na+-free media, however, the depolarization increased with Lys+ concentration up to a maximum at 10 mM and then decreased to near zero at 30 mM. These data are consistent with a model for Lys+ entry in which an anionic site of the carrier can bind either Na+ or the epsilon-NH3+ group of Lys+. In this model transport of either complex, carrier-/Lys+ or carrier-/Lys+/Na+ (and return of the carrier to the extracellular surface) is rheogenic. However, at higher Lys+ concentrations, the epsilon-NH3+ group of a second Lys+ molecule may bind to the carrier forming a complex, carrier-/2Lys+, which is not transported. PMID- 2898152 TI - Effect of active sensitization on canine airway smooth muscle responsiveness to adrenergic and cholinergic mechanisms in vitro. PMID- 2898154 TI - Fixed dose combination therapy in asthma. The positive case for future therapy. PMID- 2898153 TI - Epithelial dysfunction and airway hyperreactivity in asthma. AB - It is clear that the central airway epithelium plays an important role in restricting access of inhaled solutes to sub-epithelial airway wall structures. Non-specific airway hyperreactivity to spasmogens in asthma may result partly as a consequence of the compromise of the epithelium as a barrier to solute diffusion. However, impaired epithelial production and release of smooth muscle relaxant factor(s) may also contribute to airway hyperresponsiveness. Virally precipitated asthma also involves inflammation-induced epithelial damage. Beta adrenoceptor hypofunction induced by respiratory viruses may also contribute to bronchial obstruction. PMID- 2898155 TI - Inhibition of rat colon motility by stimulation of atypical beta-adrenoceptors with new gut-specific agents. AB - The new putative beta-adrenergic agonists SR 58306A, 2-[(7-hydroxy-1,2,3,4 tetrahydronaphth-2-yl)amino]-1-phenylethanol hydrochloride and SR 58339A, 2-[(7 hydroxy-1,2,3,4-tetrahydronaphth-2-yl)amino]-1- (3-chlorphenyl) ethanol hydrochloride, were studied in vitro in comparison with reference compounds. SR 58306A and SR 58339A, unlike isoprenaline and the beta2 selective adrenergic agonists salbutamol and ritodrine, potently inhibited rat colon spontaneous contractions (EC50 5.9 and 1.1 x 10(-7) M) without increasing guinea-pig atrium frequency or relaxing guinea-pig trachea. The nonselective beta-adrenergic antagonists alprenolol, pindolol and propranolol competitively antagonized the action of SR 58306A on the colon, which was not prevented by either of the selective antagonists atenolol (beta 1) and ICI 118551 (beta 2). In the same preparation only alprenolol competitively antagonized isoprenaline; antagonism by either pindolol or propranolol was not competitive. These results suggest that in the rat colon isoprenaline interacts with different beta-receptor subclasses, whereas our new gut-specific compounds such as SR 58306A inhibit colonic motility by selectively stimulating atypical beta-adrenoceptors. PMID- 2898156 TI - Control of alcohol addiction by SKV therapy--its action on water, food intake, brain function and cell membrane composition. AB - Alcohol being easily permeable through cell membrane causes toxic damage to many tissues. Rats drinking aqueous ethanol (25% v/v) for 120 days and 240 days showed an initial rise in body weight. The reduced rate in weight gain in chronic alcoholism is associated with a fall in food intake. Ethanol ingesting animals showed slow response to stimuli and increase in blood ethanol and serum GGTP levels. Liver plasma membrane, kidney brush-border membrane and pancreatic plasma membrane from alcoholic rats showed significant alterations in cholesterol/phospholipid molar ratio and membrane ATPases. Water retention with the enlargement of liver and kidney associated with increased fluid consumption are also seen during alcoholism. SKV by breaking alcohol dependence reduces drinking, lowers blood ethanol level and fluid intake without developing withdrawal symptoms. Restriction of ethanol intake by SKV therapy resulted in the reversal of organ enlargement and membrane composition in alcoholics. PMID- 2898157 TI - Effect of 2-pyrrolidone on the concentration of GABA in rat tissues. AB - The effects of 2-pyrrolidone, a cyclic lactam of GABA, were studied on blood and organ levels of 2-pyrrolidone, GABA, glutamic acid, glutamate decarboxylase (GAD) and GABA-transaminase (GABA-T). When administered i.p., the only significant effects observed were increases of brain and liver 2-pyrrolidone. In contrast, regular oral administration for 7 months produced significant increases of GABA and glutamic acid in brain and of glutamic acid alone in liver while GAD decreased in brain and increased in liver; GABA-T was unchanged. A new method for the synthesis of radioactive 2-pyrrolidone was set up and the enzymatic conversion of 2-pyrrolidone to GABA was measured by an original procedure. The results obtained in vitro by this method on the conversion of 2-pyrrolidone to GABA catalyzed by tissue slices, together with the observed inhibition of the GABA-dependent oxygen consumption by 2-pyrrolidone, partially explain the effects of the oral administration. PMID- 2898158 TI - Photoaffinity labeling of angiotensin II and bradykinin receptors. PMID- 2898159 TI - Class II antiarrhythmic agents. PMID- 2898160 TI - An immunofluorescent study of insulin-, glucagon-, pancreatic polypeptide- and somatostatin-containing cells in the early ovine fetal pancreas. AB - Using antisera to insulin, glucagon, pancreatic polypeptide (PP) and somatostatin, the localization and cellular distribution of the four hormones were investigated in the sheep fetal pancreas of day 40-45 gestation by immunofluorescence. All four hormones were immunolocalized at this early gestational period. The endocrine cell types had a characteristic distribution and were present in different numbers. Insulin and glucagon immunoreactive cells were seen in larger numbers compared to fetal PP and somatostatin cells and were located either in the developing islets or as single scattered cells in the epithelium of the embryonic ductules. These cells became more confined to the developing islets at later stages of gestation. In the pancreas of day 40-45 fetuses PP cells were less numerous than glucagon and insulin cells while somatostatin cells were seen rarely. However, PP and somatostatin cells became more numerous at later stages of gestation. Our studies demonstrate the presence of insulin, glucagon, PP and somatostatin within distinct cell types in the early sheep fetal pancreas. PMID- 2898161 TI - [Influence of solder on bond strength of metal/ceramic system]. PMID- 2898162 TI - Streamlining operation of an admitting service for interventional radiology. AB - The authors describe how operations of an inpatient admitting service for interventional radiology were improved by developing a clinic and hiring a physician's assistant. The service, begun in 1982, was managed by a senior radiologist and fellows. Because of increasing admissions (from a mean of 52 per year in 1982-1985 to 110 per year in 1985-1987), a 1/2-day, twice-weekly clinic was created in 1985 to evaluate new patients and perform follow-up examinations. In 1986 a physician's assistant was hired to assist in the clinic and during patient admissions. Use of the clinic and physician's assistant streamlined patient flow and management during hospitalization. This resulted in a decrease in mean length of stay for patients undergoing angioplasty (from 3.74 days in 1982-1983 to 2.41 days in 1986-1987). This decrease means cost savings for the hospital under the prospective payment system. Other benefits include improved physician-patient relationships and follow-up, new patients for colleagues (15% of patients had anatomy unsuitable for interventional procedures and were referred to staff surgeons), and increased professional fees. PMID- 2898163 TI - The Milan Congress on Sarcoidosis and Other Granulomatous Disorders. PMID- 2898164 TI - [The operating room nurse at the 89th Congress of Surgery]. PMID- 2898165 TI - Brain evolution and Alzheimer's disease. AB - It is argued that rapid evolution of the hominid brain was accomplished by the molecular mechanisms of "regulatory evolution" and "gene duplication". These genomic processes may have made newly elaborated brain regions--including the association neocortices and parts of the hippocampal formation, nucleus basalis of Meynert and amygdaloid body--vulnerable to Alzheimer's disease, by increasing the value of a disease-specific genomic character function. Trisomy 21, it is proposed, further increases this value. PMID- 2898166 TI - Peripheral vasoconstriction in patients with sleep related periodic leg movements. AB - Two patients complaining of insomnia had sleep-related periodic leg movements (nocturnal myoclonus) on polysomnographic evaluation. Both also complained of cold feet and had abnormal peripheral pulse examinations. Treatment with phenoxybenzamine, alpha-adrenergic blocker, normalized the peripheral pulse responses, reduced the complaint of insomnia, and reduced the sleep related leg movements but resulted in only mild sleep improvements. Peripheral pulse examinations of ten other patients with sleep-related periodic leg movements revealed abnormal responses in four. From these and other results, it is hypothesized that the sympathetic nervous system may mediate the periodicity of sleep related periodic leg movements. PMID- 2898167 TI - Once and twice daily doses of H2 antagonists revisited, using continuous intragastric pH monitoring. AB - Eight patients with previous duodenal ulcer in symptomatic remission underwent continuous intraluminal pH monitoring on five separate occasions to compare the effects on 24-h intragastric acidity of placebo, 300 mg ranitidine at night, 150 mg ranitidine twice daily, 40 mg famotidine at night, and 20 mg famotidine twice daily. All H2 blocker treatments were superior to placebo (p congruent to 0), whereas the twice daily doses of both ranitidine and famotidine were significantly better (p congruent to 0 and p = 0.00006, respectively) than the single ones in reducing 24-h intragastric acidity. The higher acid inhibitory effect of the twice daily dose regimens than of the single ones was evident during the daytime, whereas no difference between them was found during the nighttime (from 2200 to 0800 h). These data are at variance with those previously published, and the slight effect of the single nightly doses of H2 blockers on daytime acidity seems to confirm further that the suppression of nocturnal acidity may really be the decisive factor in the success of this dosing schedule in treating duodenal ulcer. PMID- 2898169 TI - [Pharmacotherapy of cardiogenic shock]. AB - The definition and classification of the various forms of circulatory shock are outlined, together with the causes and management of cardiogenic shock. The pharmacotherapeutic possibilities in patients with shock following myocardial infarction are discussed: over the last 15 years several alpha and beta adrenergic stimulants, as well as alpha-blocking agents, have been included in the treatment of this severe circulatory failure; today the most commonly used drugs in cardiogenic shock are dopamine and dobutamine, sometimes in combination with vasodilators. Dopamine appears to be indicated when low cardiac output, arterial hypotension and oliguria are present; dobutamine, a positive inotropic acting drug, should be used when arterial hypotension is only moderate but combined with elevated filling pressures. Despite the various therapeutic approaches the mortality of cardiogenic shock, which reaches 10-15% of patients with acute myocardial infarction, is still high (70-90%); an improvement may be expected with newer forms of therapy (fibrinolysis, dilatation). Finally, a concept for the management of cardiogenic shock following myocardial infarction is presented. PMID- 2898168 TI - Treatment of malignant endocrine pancreatic tumors with a new long-acting somatostatin analogue, SMS 201-995. AB - Ten patients with malignant endocrine pancreatic tumors were treated with SMS 201 995 at doses of 50 micrograms twice daily, administered subcutaneously. Four out of 10 patients (40%)-1 patient with the Zollinger-Ellison syndrome and 3 of 6 with the watery diarrhea syndrome--responded objectively with more than 50% reduction of peptide levels, with a median duration of 15.5 months. All four patients improved symptomatically, with decreasing dyspeptic symptoms and decreasing diarrhoea. Three additional patients had a clear relief of symptoms without an effect on tumor-secreted peptides. The disease progressed in three patients during treatment. No reduction of tumor mass was seen in any of the patients. The main side effect noted was a slight but maintained increase in fasting blood glucose in four patients. In conclusion, SMS 201-995 had a beneficial effect in more than half of the patients and seems to be a valuable adjunct to other causal therapy in this patient category, especially in acute situations and weak patients because of its very few side effects. PMID- 2898170 TI - DNA fingerprinting takes the witness stand. PMID- 2898171 TI - [Treatment of schizophrenia]. PMID- 2898172 TI - [Beta agonists]. PMID- 2898173 TI - Development and architectonics of the suprachiasmatic nucleus of rats. Immunohistochemical study. PMID- 2898174 TI - Recent advance in the study of multiple sclerosis. PMID- 2898175 TI - Immunogenetic background of intractable disorders. PMID- 2898177 TI - [The tasks of perestroika in dentistry. The resolution of the 8th All-Union Congress of Dentists]. PMID- 2898176 TI - [Use of gangliolytics in maxillofacial surgery]. PMID- 2898179 TI - [Microsurgical transplantation of the testis in cryptorchism]. PMID- 2898178 TI - Serologic HLA-DR typing is not sufficient for definition of class II compatibility. PMID- 2898180 TI - Ipecac-induced emesis and gastric lavage are equally unpleasant. AB - It has been widely held that gastric lavage is more unpleasant than ipecac induced emesis. In fact, patients are occasionally threatened with large rubber tubes in order to persuade them to drink ipecac. To confirm that this assumption exists, we asked 41 emergency physicians and nurses who had never personally undergone either procedure to estimate the discomfort of each using a 10 cm unsegmented visual analog scale. This "naive" group thought that gastric lavage would be significantly more unpleasant than ipecac-induced emesis (mean scores: lavage = 6.46, emesis = 4.94; P less than .001, paired t-test). Using the same methods, we asked 16 health professionals who had undergone both procedures as part of another study to score the recalled unpleasantness of each procedure. Among these who had actually experienced both, there was no significant difference between the mean scores for lavage (4.09) and emesis (4.62) (P greater than 0.5, paired t-test). The mean score difference (lavage minus emesis) for the "naive" group was significantly greater than for the experimental group (1.52 vs .53, P less than .001, unpaired t-test). Among normal volunteers, ipecac-induced emesis and gastric lavage are equally unpleasant gastric emptying procedures. PMID- 2898182 TI - Factors influencing the pathogenicity of Entamoeba histolytica. PMID- 2898181 TI - Fungal transformations of antihistamines: metabolism of methapyrilene, thenyldiamine and tripelennamine to N-oxide and N-demethylated derivatives. AB - 1. Strains of the fungus Cunninghamella elegans ATCC 9245 and 36112 were tested for their ability to transform the antihistamines methapyrilene (I), thenyldiamine (II) and tripelennamine (III). 2. Antihistamine metabolites were isolated by h.p.l.c., and identified by their 1H-n.m.r. and mass spectral properties. 3. All three drugs were transformed by both C. elegans strains to N oxidized and N-demethylated derivatives. Metabolism during 96 h of incubation amounted to 85% for (I), 64% for (II), and 83% for (III). Metabolites soluble in organic solvents amounted to 62% to 86% of the total metabolism; approximately 88% to 95% of the organic-soluble metabolites were N-oxide derivatives of each antihistamine. PMID- 2898183 TI - Purification of r-glutamyltranspeptidase from rat primary hepatoma tissue and preparation of a tumor associated antigen. PMID- 2898184 TI - Sulpiride in Meige's syndrome: possible role of glutamate. PMID- 2898185 TI - [Age-related changes in the blood-brain barrier in the rat with reference to methionine, lysine, glutamic acid and N-methyl-N-nitrosourea]. AB - One possible cause of the decline in brain function with aging might be an age related change in the blood-brain barrier (BBB). Therefore, we assessed the "Brain Uptake Index" (BUI) by the method of Oldendorf (1970) in 99 male Sprague Dawley rats aged 3-4 months (young), 7-11 months (adult) and 28-31 months (old) for the following compounds: methionine, lysine, glutamic acid and N-methyl-N nitrosourea (MNU). The BUIs of methionine and MNU showed marked but contrasting biphasic changes with age: the adult animals had the highest BUIs for methionine and the lowest for MNU, compared with the young and old groups. With lysine, a declining tendency with age was indicated, whereas no differences could be detected with glutamic acid. The results suggest that the BBB undergoes different changes in development and aging, leading to an optimal amino acid transport and minimum penetration of lipophilic agents (MNU) in the adult brain. Thereafter, the opposite takes place, reducing necessary transport and increasing the penetration of lipophilic compounds. PMID- 2898186 TI - [Effect of organophosphate pesticides on the function of the liver and skin via their skin resorptive uptake]. PMID- 2898187 TI - [Involvement of tyrosine hydroxylase in functional characteristics of discrete brain nuclei]. PMID- 2898188 TI - Diurnal changes of plasma and cerebrospinal fluid somatostatin and 24-h growth hormone secretory pattern in man. A study in hydrocephalic patients. AB - Somatostatin concentration was determined in plasma and in cerebrospinal fluid during a 24-h period in 7 male patients suffering from hydrocephalus of differing aetiologies. Blood and ventricular cerebrospinal fluid samples were taken every 2 h during the day (08.00-22.00 h) and every hour during the night (24.00-07.00 h). Simultaneously, plasma growth hormone levels were also evaluated. Plasma SRIH levels showed significant circadian variations with highest values in the daytime and lowest values during the night. Cerebrospinal fluid SRIH did not show any significant time-related circadian changes. Plasma GH levels showed the well known circadian pattern in the majority of patients. No significant correlation was found between the plasma GH and plasma or cerebrospinal fluid SRIH values recorded during the 24-h period. Results suggest that peripheral SRIH does not play any major role in the control of the 24-h GH secretory pattern in man. PMID- 2898189 TI - Preventive action of phentolamine on adrenaline induced blood glucose elevation in humans. AB - A comparison of the action of adrenaline infusion and a combined adrenaline + alpha blocker (phentolamine, Regitine) infusion on blood glucose (BG), plasma immunoreactive insulin (IRI), BG/IRI ratio, C-peptide, and plasma cortisol levels was made in healthy young human subjects. The purpose of the experiment was to check, whether alpha block could abolish adrenaline-induced enhancement of blood glucose levels. The results show that during enhanced adrenaline levels, the use of regitine could indeed normalize blood glucose levels, not so much by increasing the IRI secretion, but by diminishing adrenaline-induced liver glycogenolysis via alpha receptors. This could be a model to prevent stress (adrenaline) induced metabolic deviations in diabetics, especially before and during predictable stress situations, e.g. examinations or surgery. PMID- 2898190 TI - Effects of somatostatin and serotonin on calcitonin secretion from cultured rat parafollicular cells. AB - A primary culture of mammalian parafollicular cells was established from rat thyroid glands in order to investigate the effects of serotonin and somatostatin on calcitonin secretion. Minced rat thyroid glands were dissociated with collagenase and cultured in a Ham's F-12K medium supplemented with calf serum (5%), insulin (1.3 X 10(-6) mol/l), hydrocortisone (10(-8) mol/l), transferrin (6.1 X 10(-9) mol/l), and glycyl-L-histidyl-L-lysin (2.5 X 10(-8) mol/l). Immunohistochemical peroxidase-antiperoxidase method revealed that the cultured parafollicular cells were immunopositive for human calcitonin, and electron microscopy demonstrated the existence of dense secretory granules in the cultured parafollicular cells. Addition of the Ca2+ to the culture medium stimulated calcitonin secretion from the cells dose-dependently as measured by radioimmunoassay. Pre-incubation of serotonin with the cells produced higher calcitonin levels in a dose-dependent manner. On the other hand, pre-incubation of somatostatin with the cells significantly inhibited calcitonin secretion. PMID- 2898191 TI - Secretion of growth hormone-releasing hormone in patients with idiopathic pituitary dwarfism and acromegaly. AB - The plasma levels of immunoreactive-GHRH in patients with idiopathic pituitary dwarfism and acromegaly were studied in the basal state and during various tests by a sensitive and specific RIA. The fasting plasma GHRH level in 22 patients with idiopathic pituitary dwarfism was 6.3 +/- 2.3 ng/l (mean +/- SD), which was significantly lower than that in normal children (9.8 +/- 2.8 ng/l, N = 21), and eight of them had undetectable concentrations (less than 4.0 ng/l). Little or no response of plasma GHRH to oral administration of L-dopa was observed in 7 of 10 pituitary dwarfs, and 3 of the 7 patients showed a response of plasma GH to iv administration of GHRH (1 microgram/kg). These findings suggest that one of the causes of idiopathic pituitary dwarfism is insufficient GHRH release from the hypothalamus. The fasting plasma GHRH level in 14 patients with acromegaly and one patient with gigantism was 8.0 +/- 3.9 ng/l, which was slightly lower than that in normal adults (10.4 +/- 4.1 ng/l, N = 72). One acromegalic patient with multiple endocrine neoplasia type I had a high level of plasma GHRH (270 ng/l) with no change in response to L-dopa and TRH test. In 3 untreated patients with acromegaly L-dopa did not induce any response of plasma GHRH in spite of inconsistent GH release, and in 4 patients with acromegaly, TRH evoked no response of plasma GHRH in spite of a marked GH release, suggesting that the GH responses are not mediated by hypothalamic GHRH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898192 TI - Comparison of thyroid stimulating activities measured by cyclic AMP production, those by radioiodine uptake in FRTL-5 cells and TSH-binding inhibitory activities in patients with hyperthyroid and euthyroid Graves' diseases. AB - By using an assay measuring cAMP production in FRTL-5 thyroid cells, thyroid stimulating antibodies (TSab) were detected in all of 15 patients with euthyroid Graves' disease (EG) and of 26 patients with hyperthyroid Graves' disease (HG). There was no significant difference between TSab activities in EG and in HG. In an effort to elucidate why EG patients remain euthyroid in spite of having TSab, we investigated the effect of the patient's crude immunoglobulin fractions on 125I uptake in FRTL-5 thyroid cells, one of the indices of stimulation subsequent to cAMP production. The 125I uptake stimulating (IUS) activity was positive in 46.7% (7/15) of EG patients and 88.5% (23/26) of HG patients, being significantly lower in the former than in the latter (P less than 0.02). Although the IUS activities significantly correlated with TSab activities in 41 patients with EG and HG (r = 0.784, P less than 0.001), the ratio of IUS to TSab in EG tended to be lower than that in HG. TSH-binding inhibitor immunoglobulins (TBII) activities in EG patients were negative or weakly positive, being significantly lower than those in HG patients (P less than 0.001). Thus, the ratios of TBII to both TSab and IUS activities were significantly higher in HG than in EG (P less than 0.01, P less than 0.001, respectively). The in vitro IUS activities also correlated with TBII activities (r = 0.441, P less than 0.001) and in vivo 99mTc thyroid uptake (r = 0.401, P less than 0.001) in both EG and HG patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898194 TI - Two-generation study of neuroleptic isofloxythepin in rats. AB - The neuroleptic isofloxythepin was tested in a two-generation study in rats in oral doses of 0.1 mg base/kg and 1 mg base/kg. The substance was administered to male and female rats of each generation daily from the weaning onward till the conclusion of the study. The pups of two consecutive generations F0 and F1 were surveilled always in two litters. There were assessed the numbers and body weights of the pups from birth till the weaning, the postnatal developmental milestones, and the results of neuromuscular and locomotor activity tests. In the parents the fertility parameters were followed. --Isofloxythepin at higher dosage, 1 mg/kg, influenced the estrous cycles in the females, prolonging the diestrus stage, but exerted no significant effects upon their fertility and pregnancy. The growth of the offspring of parents treated with isofloxythepin in both generations was slightly retarded. In the F0 generation the pup's mortality increased in the perinatal period. The sedative effect of the neuroleptic manifested itself by a lowering of the locomotor activity. The proved effects of isofloxythepin in the higher dose are mostly connected with the drug's neuroleptic properties. Analogous effects of other substances of this type have been reported in the literature, too. In the course of the study the effects of isofloxythepin did not intensify from the first to the second generation. PMID- 2898193 TI - Psychopharmacologic facilitation of psychosocial therapy of violence and hyperkinesis. AB - Experiments on naturally occurring hyperkinetic and violent dogs and cats demonstrated the usefulness of low dosages of amphetamine (0,2-1,0 mg/kg per os) in inhibiting these nonadaptive forms of behavior, permitting the development of discriminated Pavlovian and operant conditional responses. When amphetamine therapy was combined systematically with conditioning experiments and psychosocial therapy, for long enough periods of time (many weeks), the beneficial effects of this drug persisted in the nodrug state, i.e. the learning was not state-dependent. Amphetamine also ameliorated significantly conditional emotional visceral responses in dogs with low adaptation to psychologically stressful situations. The same low dosage of amphetamine which improved the behavior and learning of hyperkinetic and violent dogs disrupted the behavior and produced disorientation in normal dogs with previously stable conditional responses. PMID- 2898195 TI - On the special occasion of the 40th anniversary of the founding of Pergamon Press: a brief historical background of Acupuncture & Electro-Therapeutics Research. The International Journal. PMID- 2898196 TI - Acupuncture anesthesia in thymectomy on myasthenia gravis patients. AB - Thymectomy is often successful as treatment for the autoimmune disease myasthenia gravis. One complication of the operation on such patients is respiratory difficulty especially post-operatively, due to interference with the already disturbed transmission of signals along damaged nerve-endings. Acupuncture anesthesia offers a solution to that problem. In this series of 90 patients, the results of operation under conventional general anesthesia were compared with those under acupuncture anesthesia. It was found that patients in the latter group suffered fewer complications. PMID- 2898197 TI - Acupuncture for poison ivy contact dermatitis. A clinical case report. AB - Poison ivy contact dermatitis is fairly common in the suburbia of this country among amateur gardeners and children. It commonly inflicts its poison on the exposed parts of the limbs. The vesicular or bullous skin lesions are quite disturbingly itchy. Scratching the itchy lesions often spreads the condition by transplanting the remanent resinous toxin to other parts of the body. Though they are usually self-limiting, the intense itch is the main motivation for a patient to seek medical care. The conventional treatment is basically ineffective. During the summer of 1987 we treated four such cases of dermatitis with acupuncture upon their request to mollify their unbearable itch. They originally consulted with us for other problems. There were three males and one female. Their ages were between 29 and 63. Three cases were relatively mild and the fourth one was fairly severe. In the milder cases, their itch subsided in a few hours and skin lesions were healed in about two days after one treatment. In the severe case the itch subsided in about two days and most of the skin lesions dried up in four days after the first treatment and were healed almost completely after three sessions of acupuncture treatment. The plausible anti-inflammatory mechanism of acupuncture with the involvement of ACTH and/or cortisol was discussed. PMID- 2898198 TI - The use of the "Bi-Digital O-Ring Test" to determine whether or not to give acupuncture in pain conditions. AB - The "Bi-Digital O-Ring Test" was used as a guide in determining the modality of treatment of pain conditions. Seven cases are presented in which patients came primarily for acupuncture. They were not treated with acupuncture; instead, they were given antibiotic therapy because the Bi-Digital O-Ring Test had revealed the presence of infection. The antibiotic therapy resulted in dramatic improvement. PMID- 2898199 TI - Regeneration in the mammalian nervous system using applied electric fields: a literature review. AB - The application of weak electric fields on the damaged peripheral and central nervous systems will promote recovery of function in animal models. The effect of the electric field appears to facilitate the growth and orientation of regenerating neurites towards the cathodal pole in a DC field. Thus, provided the correct parameters are utilized, facilitation of regeneration in the human peripheral and even central nervous system appears possible. PMID- 2898200 TI - Overview of acupuncture in the United States. PMID- 2898201 TI - Effects of dexamethasone on electroacupuncture analgesia and central nervous system metabolism. AB - Many reports have indicated that electro-acupuncture analgesia (EAA) was mediated by endorphins. Among them is B-endorphin which can be released from the anterior lobe of the pituitary. To examine the role of B-endorphin in EAA and observe CNS metabolic (functional) and behavioral effects of dexamethasone the present study employed the (14C) 2-deoxyglycose (2DG) method. Seventeen adult male Sprague Dawley rats in five groups received the following different types of somesthetic stimulation to examine the local cerebral glucose utilization (LCGU) and tail flick response latency: control group (N = 3), pain group (N = 4), EA group (N = 3), pain + EA group (N = 3; from another ongoing study) and dexamethasone group (N = 4). Dexamethasone reduced tail-flick response latency in response to electroacupuncture, and produced metabolic (functional) changes in a number of CNS structures implicated in electroacupuncture produced analgesia effects (some changes were statistically significant, many others were not). Specific brain structures exhibiting statistically significant changes (p less than 0.05) in LCGU when compared to the pain + EA group are: the parafascicular and habennlar nuclei of the thalamus and the posterior cingulate gyrus. In comparison of dexamethasone group with the other four experimental groups of rats, the following trend in LCGU changes was observed: pain + EA group greater than pain group = EA group = dexamethasone group greater than control group. In addition, dexamethasone had a sedative effect. The results suggest that dexamethasone is reducing EAA and having suppressive effects on CNS metabolism and behavior. PMID- 2898202 TI - The role of beta-adrenergic receptors in the cardiac output response during carbon monoxide hypoxia. PMID- 2898203 TI - The physiology and biochemistry of pili. PMID- 2898204 TI - Anxiety disorders. PMID- 2898205 TI - Antihypertensive drug therapy and arrhythmia risk. PMID- 2898206 TI - Spontaneous neurohormonal fluctuation in chronic congestive heart failure. PMID- 2898207 TI - Cardiac catheterization by nonphysicians. PMID- 2898208 TI - Effect of flestolol on ventricular rate during atrial fibrillation in Wolff Parkinson-White syndrome. AB - The ultrashort-acting beta blocker flestolol was studied during atrial pacing and atrial fibrillation (AF) in 10 patients with Wolff-Parkinson-White syndrome. Flestolol was given as a 100-micrograms/kg bolus followed by a 10 micrograms/kg/min infusion for 15 minutes. The drug did not alter the antegrade effective refractory period of the accessory pathway or the atrial paced cycle length at which block occurred in the accessory pathway. After flestolol, the percent of preexcited QRS complexes during AF increased (60 +/- 10 vs 87 +/- 5%, p = 0.01). Despite this, the ventricular rate slowed, with increases in mean RR interval (382 +/- 20 vs 416 +/- 22 ms, p = 0.02) and in the shortest interval between preexcited QRS complexes (251 +/- 18 vs 270 +/- 17 ms, p less than 0.01). The effect of isoproterenol 3 to 5 micrograms/min was studied in 5 patients. During atrial pacing, isoproterenol decreased the antegrade refractory period and the atrial paced cycle length of block in the accessory pathway (p less than or equal to 0.05). During AF, it decreased the percent of preexcited QRS complexes, mean RR interval and shortest interval between preexcited QRS complexes (p less than 0.05). Flestolol reversed the effects of isoproterenol both during atrial pacing and AF. Thus, flestolol does not alter conduction over the accessory pathway during atrial pacing, but during AF it slows conduction over the accessory pathway and prevents isoproterenol-mediated increases in ventricular rate. This suggests that in patients with Wolff-Parkinson-White syndrome sympathetic stimulation after the onset of AF enhances conduction over the accessory pathway and is an important determinant of ventricular rate. PMID- 2898209 TI - Cardiovascular pharmacology of dopexamine in low output congestive heart failure. AB - Dose-response infusions (0.25 to 4.0 micrograms/kg/min) and extended infusions of dopexamine, a new synthetic catechol with beta 2 adrenergic and dopaminergic agonist effects, were performed in 12 patients with low output congestive heart failure (CHF). The central and regional hemodynamic effects and responses in renal function were determined and compared with those of saline-placebo control patients in a randomized, double-blind, crossover design. Dopexamine significantly increased cardiac output at a dose greater than or equal to 0.25 micrograms/kg/min secondary to an increase in stroke volume at greater than or equal to 0.25 micrograms/kg/min and heart rate at greater than or equal to 0.50 micrograms/kg/min. Dopexamine evoked a significant decrease in systemic and pulmonary vascular resistances, with mild reductions noted for systemic and pulmonary diastolic pressures. Right and left ventricular filling pressures decreased over the entire dose range of dopexamine concomitant with a demonstrable improvement in the indexes of ventricular performance. Dopexamine preferentially increased visceral (renal, hepatic-splanchnic) blood flow over that of limb. Urine volume and sodium excretion increased slightly with dopexamine. Dopexamine elicits rather prominent vasodilating effects (particularly of visceral vascular beds), some positive inotropy and chronotropy and favorable responses in renal function. PMID- 2898210 TI - Collagenous enterocolitis: a case of collagenous colitis with involvement of the small intestine. AB - A 78-yr-old previously well caucasian female presented with a 6-wk history of profuse watery diarrhea and weight loss. Clinical investigation showed evidence of mild malabsorption. Multiple biopsies of colonic mucosa revealed a wide subepithelial band of collagen typical of collagenous colitis. Duodenal biopsies showed similar collagen deposition and partial villous atrophy. Some amelioration of symptoms occurred with sulfasalazine therapy. This is the first reported case of collagenous colitis with histological evidence of small intestinal involvement. At least in some patients, collagenous colitis and collagenous sprue appear to be manifestations of a single disease. For such cases, the term collagenous enterocolitis is suggested. PMID- 2898211 TI - Production of transforming growth factor-beta activity by Ki-1 positive lymphoma cells and analysis of its role in the regulation of Ki-1 positive lymphoma growth. AB - The growth of activated human T lymphocytes in response to interleukin-2 (IL-2) is suppressed by transforming growth factor-beta (TGF-beta). This study presents data that show a diminished response of two human lymphoma cell lines to physiologic regulation by TGF-beta. Cell line L-428 was derived from the malignant pleural effusion of a patient with far advanced nodular sclerosing Hodgkin's disease and has been shown to have clonal gene rearrangements characteristic of both B and T lymphocytes. Cell line Mac-1 was derived from the blood of a patient with clinically indolent cutaneous T-cell lymphoma. Both cell lines express the Hodgkin's disease associated antigen, Ki-1. These Ki-1 positive lymphomas are shown to secrete TGF-beta into serum-free culture media. The addition of picogram quantities of exogenous TGF-beta to cell cultures of indolent Ki-1 lymphoma (Mac-1) suppresses IL-2-dependent mitosis; however, the suppression is less than 45%. This suppression correlates with a decrease in the number of IL-2 receptors. No inhibition of Ki-1 positive Hodgkin's cells (L-428) was observed, and proliferation dependent on polyclonal IL-2 was either not affected or was slightly potentiated by TGF-beta. Receptor analysis indicates the absence of IL-2 and TGF-beta receptors on L-428 cells. Thus, these Ki-1 lymphomas derived from activated lymphocytes appear to secrete TGF-beta activity but continue to proliferate because of defective suppression of IL-2 (and related lymphokine)-dependent DNA synthesis. PMID- 2898212 TI - Drug-induced dystonia in young and elderly patients. AB - This retrospective study examined the common notion that neuroleptic-induced dystonia is less frequent in elderly patients. The hospital records of 45 young patients and 45 elderly patients were reviewed. Thirty-one percent of the young patients developed dystonia, compared to 2% of the elderly patients. This significant difference did not appear to be the result of types of neuroleptics used, dose, or concomitant administration of anticholinergic drugs. PMID- 2898213 TI - Exacerbation of psychosis after discontinuation of carbamazepine treatment. AB - Carbamazepine alone or carbamazepine plus neuroleptic was administered to 20 chronic schizophrenic patients. Upon abrupt discontinuation two of the 20 patients had exacerbations of their psychoses characterized by paranoia, hostility, and agitation. The authors discuss the possibility of a carbamazepine withdrawal syndrome. PMID- 2898214 TI - Beta blockers in neuroleptic-induced akathisia. PMID- 2898215 TI - Pharmacologic strategies in schizophrenia. PMID- 2898216 TI - Divided dose for methadone maintenance patients. PMID- 2898217 TI - Spontaneous rupture of the plantar fascia. AB - In this study, rupture of the plantar fascia was seen in five feet, of which four had had plantar fasciitis. At the time of the injury, which is an acceleration type of motion, there is severe pain in the heel followed by the development of ecchymosis in the sole and toward the heel of the foot. With conservative symptomatic care, the acute symptoms as well as the plantar fasciitis symptoms subside, generally allowing full activity in 3 to 4 weeks. PMID- 2898218 TI - Structural elucidation of N-terminal post-translational modifications by mass spectrometry: application to chicken enolase and the alpha- and beta-subunits of bovine mitochondrial F1-ATPase. AB - Peptides generated from enzymatic hydrolysis of chicken enolase and the alpha- and beta-subunits of bovine F1-ATPase were analyzed by mass spectrometry to determine the nature of their modified N-termini. In the case of chicken enolase, a peptide was isolated from a Staphylococcus aureus proteinase digest by HPLC and analyzed directly by fast atom bombardment mass spectrometry (FABMS). In conjunction with mass spectral evidence obtained from the methyl ester derivative and a secondary tryptic peptide, a structure is proposed containing an N-acetyl serine at the N-terminus. The alpha-subunit of bovine mitochondrial ATPase was chromatographed by HPLC after S. aureus proteinase digestion and a single peak was analyzed on the basis of predicted retention times. A Mr 716 was determined by FABMS and pyrrolidone carboxylic acid was deduced on the basis of its amino acid composition and partial Edman sequence data. The beta-subunit of ATPase produced a series of closely eluting peaks on HPLC after limited digestion with trypsin of the alpha 2 beta 2 complex. These peptides were analyzed by both Edman degradation and FABMS. These data showed the N-terminus to be frayed with N terminal sequences beginning in pyro-Glu-Ala-Ser, Gln-Ala-Ser, Glu-Ala-Ser, Ala Ser, and Ser but with no N-acetyl-Ser as was previously thought. PMID- 2898219 TI - Anesthetic and hemodynamic effects of the stereoisomers of medetomidine, an alpha 2-adrenergic agonist, in halothane-anesthetized dogs. AB - The anesthetic-sparing and hemodynamic effects of the stereoisomers of the highly selective alpha 2-adrenergic agonist medetomidine were studied in halothane anesthetized dogs. Male beagles were anesthetized with halothane in oxygen. After a 2-hour equilibration period, halothane MAC and baseline hemodynamic functions were determined. DL-(n = 7), D- (n = 5), or L-medetomidine (n = 5) at 1, 3, and 10 micrograms/kg was administered via a right atrial port over 15 minutes while each dog was given halothane at the MAC dose for that animal. Twenty minutes after the end of infusion (when the hemodynamic variables were stable), hemodynamic function was reassessed. Halothane MAC was then redetermined. MAC for halothane significantly decreased after DL-medetomidine administration in a dose dependent fashion to the extent that at the highest dose (10 micrograms/kg) the halothane MAC was less than 0.1%. This effect could be mimicked by the D-isomer, whereas the L-isomer was without effect. Neither isomer changed the mean arterial pressure, whereas only the D-isomer significantly decreased heart rate and cardiac output. Medetomidine, the highly selective alpha 2-adrenergic agonist, reduces the MAC for volatile anesthesia by a greater degree than with any other physiologic, pharmacologic, or pathologic intervention thus far reported. The fact that this effect is stereospecific suggests a structure activity relation that can be accounted for by a homogeneous receptor population. The role of medetomidine as a supplemental anesthetic agent appears promising and requires further investigation. PMID- 2898221 TI - Anesthesia for a patient with polymyositis undergoing myectomy of the cricopharyngeal muscle. PMID- 2898220 TI - A comparison of the antinociceptive and behavioral effects of intrathecally administered opiates, alpha-2-adrenergic agonists, and local anesthetics in mice and rats. AB - This study was undertaken to compare the antinociceptive and behavioral effects of intrathecally administered opiates, alpha-2-adrenergic agonists, and local anesthetics injected by lumbar puncture in the mouse and rat. Antinociception was determined by observing the response to a clamp applied to the tail (Haffner test) of the mouse and by the rat tail-flick test; log dose-response curves for antinociception were generated for each drug in each test. Motor coordination and other behavioral effects were also observed. Morphine and fentanyl (mu-opiate agonists) as well as ethylketocyclazocine (EKC) and U50488H (kappa-opiate agonists), together with buprenorphine (partial mu-opiate agonist) and the alpha 2-adrenergic agonist clonidine, all produced antinociception in both species without causing significant behavioral or motor dysfunctions at antinociceptive doses. Xylazine (also an alpha-2-adrenergic agonist), ketamine, procaine, and lidocaine inhibited responses but only at doses that also produced motor impairment or paralysis. Nalbuphine (mixed opiate agonist-antagonist) was without any effect in both species. These data suggest that the mu- and kappa-opiate agonists and clonidine are the preferred agents for producing antinociception without compromising motor function. PMID- 2898222 TI - Mechanical and bone ingrowth properties of a polymer-coated, porous, synthetic, coralline hydroxyapatite bone-graft material. AB - CHAG, that is, porous hydroxyapatite hydrothermally converted from the calcium carbonate exoskeleton of a coral (genus Goniopora), has been shown to be effective as a scaffold for bone ingrowth. The large pores in the material, however, resulted in low compressive strengths. Compressive testing was performed to assess the changes in mechanical properties by coating the internal surfaces of CHAG with DL-PLA. Plugs of CHAG with thick (3:1 chloroform to DL-PLA by weight), medium (10:1), and thin (30:1) coatings as well as uncoated CHAG were then implanted transcortically in the proximal third of the diaphysis of rabbit tibiae to assess the in vivo response. The mechanical tests demonstrated significantly improved compressive strength, stiffness, and energy absorption for coated specimens compared with uncoated specimens. Coated specimens were not significantly different from canine tibial cancellous bone in strength and stiffness although they achieved only 36% of the energy absorption capacity. Specimens from rabbit tibiae were harvested at 3, 12, and 24 weeks for interface shear strength determination and contralaterally for histological and histomorphometric assessment. At 12 weeks, uncoated CHAG plugs developed an average ultimate interface shear stress of 26.7 MPa compared with 17 MPa for specimens with 30:1 coatings and 8 MPa for specimens with 10:1 and 3:1 coatings. At 24 weeks, there were no significant differences in shear stress between any of the specimens. Histomorphometric assessments showed that the ratio of area fraction of new bone to area fraction of new bone and void space increased from 68-70% for specimens with 3:1 and 10:1 coatings at 3 weeks to 85.5-89.5% at 24 weeks. In comparison, uncoated and 30:1 specimens had area fraction ratios of about 82% at 3 weeks and 93% at 24 weeks. Histologic sections demonstrated direct apposition of new bone to both the coating and the hydroxyapatite as well as degradation of the coating. PMID- 2898223 TI - Structural basis for arachidonic acid second messenger signal in gamma-interferon induction. PMID- 2898225 TI - Intrathecal somatostatin. PMID- 2898224 TI - Vasomotor effects of leukotrienes C4 and D4 on cavian pulmonary artery and aorta. Characterization and mechanisms. PMID- 2898226 TI - Neuroactive substances in cerebrospinal fluid. Normal and pathological regulatory mechanisms. PMID- 2898227 TI - Intracerebroventricular bethanechol chloride administration in Alzheimer's disease. AB - In June 1983 we began evaluating intracerebroventricular (ICV) cholinergic drug infusion in patients with biopsy-documented Alzheimer's disease (AD). An initial trial in four patients showed this treatment approach to be feasible, but objective improvement in cognitive or social function was not documented. A double-blind, placebo-controlled crossover study involving a larger number of patients has since been done. The results of this study, presented here, document a statistically significant improvement in some neuropsychological test results during periods of drug infusion. However, the degree of improvement is not sufficient to justify further treatment with the presently available drug, bethanechol chloride. PMID- 2898228 TI - New intrathecal drugs in Alzheimer's disease and psychometric testing. AB - Bethanechol chloride, a muscarinic agonist, was administered intrathecally to a sample of AD patients in double-blind crossover and open escalating-dose trials. There was a modest amelioration of disturbed behavior at a moderately high dose level, but no improvement in memory or cognition was seen at any dose. At the highest dose, cognition deteriorated. These findings, in conjunction with the results of the multicenter trial described by Harbaugh, suggest that the clinical efficacy of bethanechol in AD is limited. The disappointing results of trials with varied cholinomimetic therapies suggest that more than one biochemical abnormality is responsible for the AD dementia. The neuropeptide, somatostatin, is also reduced in AD, and the level of reduction is correlated with the degree of dementia. Manipulation of this transmitter, alone or in conjunction with acetylcholine, would appear to be a next logical step in the development of an effective neurotransmitter replacement therapy for AD. Implanted drug pumps will be needed for such clinical trials. The naturally occurring somatostatin-14 is not suitable because of its short half life. Sandostatin, an analog, is chemically stable and not metabolized by brain tissue. It does not cross the blood-brain barrier so that intrathecal administration is necessary. Pharmacological research in AD is complicated by a variety of psychometric problems including the criterion-related and construct validity of the outcome measures. Patients differ in their tolerance of various therapeutic agents and in the extent of the neurochemical pathology. It is critically important, therefore, to evaluate individual, as well as group, responses to treatment. The telephone log method may provide a useful way of generating enough observations for single subject analyses without overburdening the patient with repeated testing. PMID- 2898229 TI - Parkinsonism: candidate disorder for implanted pumps? PMID- 2898230 TI - Dorsal horn neurophysiology of pain. PMID- 2898231 TI - Receptors in the dorsal horn and intrathecal drug administration. PMID- 2898233 TI - Pharmacology of dynorphin. AB - Like other opioids, the dynorphins play a role in wide variety of physiological parameters, including pain regulation, motor activity, cardiovascular regulation, respiration, temperature regulation, feeding behavior, hormone balance, and the response to shock or stress. The dynorphins are unusual if not unique, however, in that they frequently modulate the activity of other opioids, rather than having direct effects themselves. Thus, they are not analgesic in brain, yet they antagonize opioid analgesia in naive animals and potentiate it in tolerant animals. They have little or no effect by themselves on temperature regulation or respiration, but they enhance the acute effects of morphine on these parameters. Their beneficial effects on stroke are like those of opioid antagonists rather than like agonists. Consistent with such a wide variety of physiological effects, the dynorphins bind to all three of the major opioid receptor types in brain, mu, delta, and kappa, though they exhibit some preference toward kappa sites. They also seem to interact with other physiologically relevant sites; though on the basis of their sensitivity to des-Tyr fragments of dynorphine and/or their insensitivity to naloxone, these sites have been termed "non-opioid". No second messenger systems have been directly associated with dynorphine binding, but several likely candidates exist. PMID- 2898232 TI - Diagnosis of familial hypercholesterolaemia using DNA probes for the low-density lipoprotein (LDL) receptor gene. AB - Familial hypercholesterolaemia (FH) is one of the most commonly inherited diseases. It is characterised by an abnormal LDL receptor resulting in a selective elevation of serum LDL and cholesterol levels. The correlation between FH and premature heart disease means that these patients contribute significantly to the number of individuals presenting with coronary heart disease. In the work described here cDNA probes to LDL-receptor were used to assess the usefulness of recombinant DNA technology to diagnose familial hypercholesterolaemia. A 3' probe to the LDL-receptor which detects a restriction fragment length polymorphism (RFLP) in linkage disequilibrium with normal and mutant LDL-receptor genes, was found to be potentially informative in 20% of the families studied. In addition a 5' probe to the LDL-receptor may be capable of directly detecting mutations in some 6% of families. We suggest that until further work has established other RFLP's or oligonucleotide probes are synthesised to directly detect mutant LDL receptor genes, recombinant DNA technology is only of limited value for diagnosing familial hypercholesterolaemia. PMID- 2898234 TI - In vivo assessment of neurotransmitter biochemistry in humans. PMID- 2898235 TI - Gastric H,K-ATPase as therapeutic target. PMID- 2898236 TI - Regulation of the release of coexisting neurotransmitters. PMID- 2898237 TI - Neuroleptics and neuroendocrine function. AB - Neuroleptics have been developed primarily to treat psychoses, but they have become invaluable research tools. Because of their selective action on DA receptors, neuroleptics are commonly employed to study the function and regulation of DA neurotransmission. The relationship between the antipsychotic efficacy and the DA receptor affinity of the various neuroleptic drugs has lead to the development of new DA antagonists in hopes of discovering novel antipsychotic agents. This approach has produced interesting new compounds selective for the DA receptor subtypes. The use of DA receptor antagonism as a measure of the potential antipsychotic efficacy of a compound will undoubtedly change as the mechanisms behind the antipsychotic actions of neuroleptics become better understood. Although endocrine side effects of neuroleptic administration are undesired in the clinic, they have provided insight into the neuroendocrine regulation of pituitary hormones. Through the use of neuroleptics, DA neurons in the hypothalamus have been shown to play a role in the regulation of prolactin, GH, and TSH secretion. The ability of DA to act at the pituitary and thereby inhibit the secretion of these three hormones suggests that other regulatory factors must provide the specificity needed for the differential secretion of the individual hormones during varying physiological states. Future research will certainly explore the interactions of DA and these regulatory factors at the pituitary. The role of DA in neuroendocrine regulation is not limited to the pituitary. The presence of DA neurons within the hypothalamus offers the possibility of DA regulation of hypothalamic neurosecretory activity. PMID- 2898238 TI - The coronary-subclavian steal syndrome: report of a case and recommendations for prevention and management. AB - The coronary-subclavian steal syndrome involves the siphoning of blood from the myocardium through an internal mammary artery graft because of a proximal subclavian artery stenosis or occlusion, and results in myocardial ischemia. With the increased use of the internal mammary artery for myocardial revascularization, the potential exists for recurrence of angina pectoris in patients who have or in whom develops high-grade stenosis or occlusion of the subclavian artery, because of the coronary-subclavian steal syndrome. The coronary-subclavian steal syndrome can be prevented by the identification of patients with or at risk to develop subclavian artery occlusive disease. All patients undergoing cardiac catheterization prior to coronary artery bypass grafting in which use of the internal mammary artery is anticipated should be evaluated for the presence of upper extremity and cerebrovascular ischemia, the presence of cervical or supraclavicular bruits, and an upper extremity blood pressure differential of 20 mm Hg or greater. Patients with these findings or with evidence of diffuse atherosclerotic vascular disease should have brachiocephalic arteriography at the time of coronary arteriography to identify significant subclavian artery occlusive disease. When this is demonstrated, use of the internal mammary artery as a free graft instead of an in situ graft or use of saphenous vein grafts is indicated. Patients in whom recurrent angina develops following coronary artery bypass grafting that included an internal mammary artery graft should have coronary arteriography to evaluate the presence of coronary-subclavian steal syndrome, and brachiocephalic arteriography. Carotid subclavian bypass grafting, probably best done with a prosthetic conduit, is the procedure of choice for management of the coronary-subclavian steal syndrome. PMID- 2898239 TI - Enhancement of desynchronized sleep signs after microinjection of the beta adrenergic antagonist propranolol in the dorsal pontine tegmentum. PMID- 2898240 TI - Desynchronized sleep suppression after microinjection of the beta-adrenergic agonist isoproterenol in the dorsal pontine tegmentum. PMID- 2898241 TI - Necrotizing arteritis of the vermiform appendix. A clinicopathologic study of 12 cases. AB - Necrotizing arteritis of the vermiform appendix (NAVA) is an uncommon condition. There are conflicting reports in the literature about its relationship to systemic polyarteritis nodosa (PAN). In this study, 12 cases of NAVA are described, constituting 0.28% of histologically examined appendixes. Nine of the patients were followed up for a mean of 6.8 years. Systemic necrotizing arteritis was found in three cases, all of which were complicated by secondary ulceration or infarction of the colon. The results strengthen the association between NAVA and systemic PAN. However, it is more meaningful to relate NAVA to the broader group of necrotizing vasculitides rather than exclusively to classic PAN. PMID- 2898243 TI - The effect of opiates upon prostatic carcinoma cell growth. AB - The effect of opiate receptor agonists upon cell growth of the prostatic carcinoma cell line DU145 were studied. Dynorphin-A increased growth significantly with a peak response at 10(-13) M, of 21 +/- 4% (mean +/- SEM). The dose response curve had a typical inverted-U shape. Dynorphin fragments 1-13 and 1-7 also increased growth at 10(-13) M, while the 2-13 fragment failed to increase growth. Naloxone increased growth at high concentration (10(-7) M) suggesting a stimulatory effect, while at the same time blocking the effect of dynorphin-A. This data demonstrates that agents which stimulate opiate receptors, especially the kappa receptor agonist dynorphin, increase the growth of prostatic carcinoma, and that this effect is controlled by changes at the N-terminal end of the peptide. This effect is blocked by Naloxone. PMID- 2898242 TI - Adhesin-receptor interactions mediating the attachment of pathogenic Escherichia coli to chicken tracheal epithelium. AB - Specific adherence of pathogenic Escherichia coli (serotypes O1, O2, and O78) to chicken tracheal epithelium was investigated using adherence-inhibition procedures. The role of pilus as adhesin was studied by blocking the pilus with antipilus antibodies. The nature of the host cell receptor was determined by blocking bacterial adhesion with specific carbohydrates or lectins and destroying the receptor with sodium metaperiodate. Antipilus antibodies to all three serotypes significantly (P less than or equal to 0.05) inhibited their adherence. Sodium metaperiodate considerably inhibited the adhesion of all three serotypes, indicating a role for monosaccharides in the host cell receptor. D-Mannose and its derivative methyl-alpha-D-mannopyranoside inhibited the adhesion of serotypes O1 and O78, indicating a role for these sugars in the host cell receptor; this was further supported by the inhibition of both serotypes after treatment of tracheal epithelium with concanavalin A. None of the sugars or lectins used inhibited adhesion of serotype O2. PMID- 2898244 TI - A controlled trial comparing sulfasalazine, gold sodium thiomalate, and placebo in rheumatoid arthritis. AB - One hundred eight-six patients with active rheumatoid arthritis were evaluated in a double-blind, randomized study that compared treatment with sulfasalazine (SSZ) (2 mg/day), gold sodium thiomalate (GST) (50 mg/week), and placebo (PBO). The 37 week course of therapy was completed by 109 patients. While marked improvement was seen in all 3 treatment groups, the only statistically significant differences between SSZ or GST and PBO were in a decreased erythrocyte sedimentation rate and increased grip strength in the right hand. GST is known to be superior to PBO, and the response of the GST-treated group was similar to that seen in other trials. The response of the PBO group, however, was much greater than in other placebo groups we have studied. SSZ was similar in efficacy to injectable gold, but was better tolerated. Because of adverse drug reactions (most commonly, rash, stomatitis, and proteinuria), 41% of patients were withdrawn from the GST treatment. Untoward drug effects (most frequently, rash and gastrointestinal distress) caused 16% of patients to be withdrawn from SSZ therapy. PMID- 2898245 TI - [Impromidine-analogous guanidines: synthesis and activity at the histamine H2 receptor. 29. Histamine analogs]. AB - 19 impromidine analogous guanidines were synthetized by acid hydrolysis of the corresponding N-cyanoguanidines. The guanidines were tested on the isolated spontaneously beating guinea-pig atrium for histamine H2-receptor affinity. Lengthening the ethyl chain of cysteamine by one methylene group leads to partial agonists of decreased activity. Impromidine congeners containing a branched cimetidine side chain prove to be potent H2-agonists with maximal or near maximal response. Affinity ratios in favour of the (R)-configurated enantiomers are moderate but clearly significant. The interaction between the affinity contributing moiety and the complementary receptor area shows a lower degree of stereoselectivity than does the efficacy contributing (imidazole-4-yl)propyl substituent of impromidine and sopromidine, respectively. Homoisohistamine derivatives dramatically lose both efficacy and affinity. PMID- 2898246 TI - Effect of the H2-blocker famotidine on gastric mucosal prostaglandin levels in water immersion stress in rats. AB - A quantitative and rapid method was developed for determination of tissue prostaglandin (PG) levels using reverse phase high performance liquid chromatography. Using this method, we investigated the effects of famotidine (YM 11170), an H2-blocker, on changes in gastric mucosal PG levels induced by water immersion stress in rats. Gastric mucosal phospholipase (PLase) activity was also estimated. Four kinds of PGs, i.e., 6-keto-PGF1a, PGE2, PGF2a, and PGD2 were detected in gastric mucosa. 6 h water immersion stress induced decreases in all of them at a similar degree, the reduction being about 70% of the control value. Decreases in PLase activity were also observed in rats with 6 h stress. Pretreatment with famotidine prevented decreases in levels of PGs, which are known to have cytoprotective effect, and also maintained PLase activity. These results indicate that famotidine exerts its anti-ulcer action via maintenance of PG levels and PLase activity. PMID- 2898247 TI - Antisecretory and antiulcer activities of a potent new histamine H2-receptor antagonist with an intermediate duration of action. AB - The antisecretory activities of 4-(dimethylamino)- N-[2-[3-[3-(1 piperidinyl)methyl]phenoxy]propyl]amino]- 1,2,5-thiadiazol-4-yl]amino]ethyl] butanamide, S-oxide (AY-29,315) and ranitidine were determined in the rat, dog and monkey. In conscious, chronically cannulated rats, AY-29,315 was 10 and 208 times more potent than ranitidine as an inhibitor of spontaneous gastric acid secretion by the p.o. and i.v. routes, respectively. Tolerance did not develop in the conscious rat with either compound when administered for 8 consecutive days at doses equivalent to 4 times their antisecretory ED50. In lumen-perfused, anesthetized rats, AY-29,315 i.v. was 44 times more potent than ranitidine as an inhibitor of dimaprit-induced acid secretion. In the gastric fistula dog, AY 29,315 was 7.5 times more potent than ranitidine as an inhibitor of dimaprit induced secretion by the i.v. route but 3 times less potent by the oral route. In the monkey, against dimaprit, AY-29,315 was 3 and 12 times more potent than ranitidine by the oral and i.v. routes, respectively. p.o./i.v. ratios indicate that, relative to ranitidine, the bioavailability of AY-29,315 by the oral route was low, particularly in the dog. In the dog, at 4 times the oral ED50 dose, the antisecretory effect of ranitidine lasted 190 +/- 3 min, while that of AY-29,315 lasted more than 9 h. AY-29,315 was 8 times more potent than ranitidine as an inhibitor of acetylsalicylic acid-induced ulcers in the rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898248 TI - Putative neurotransmitters in the red nucleus and their involvement in postlesion adaptive mechanisms. AB - A variety of putative neurotransmitters has been described in the red nucleus (RN). Measurement of neurotransmitter biochemical markers and study of their specific localizations using morphological techniques in lesion and deafferentation of the RN indicate the participation of glutamate (Glu) in corticorubral transmission and the presence of GABA in RN intrinsic neurones. The cerebellorubral projection may contain at least two populations of fibres, the one using acetylcholine and the other Glu as neurotransmitter. The presence of a serotoninergic input was also demonstrated. Selective deafferentations of the RN, particularly from its cerebellar input, result in biochemical and immunohistochemical responses indicative of increased corticorubral glutamatergic and local GABAergic transmission. These adaptive changes of neuronal transmission as well as the previously described sprouting of corticorubral nerve terminals may contribute to functional recovery after cerebellectomy in adult animals. PMID- 2898249 TI - Disappearance of CD4-lymphocyte circadian cycles in HIV-infected patients: early event during asymptomatic infection. AB - Circadian variations have been observed in peripheral blood lymphocyte counts in normal subjects; they usually reflect variations in absolute CD4-cell count. For this population, nadir occurs around 0800 h (basal value) and the peak value occurs at midnight (1.6 times the 0800-h value). This cycle is thought to be of major importance in the efficacy of the immune response because it expresses the migration of lymphocytes into lymphoid organs. PMID- 2898250 TI - Veto cells. PMID- 2898251 TI - Structure, organization, and regulation of the complement genes. PMID- 2898252 TI - V genes encoding autoantibodies: molecular and phenotypic characteristics. PMID- 2898253 TI - Haemorrhagic fever with renal syndrome: a disease of world-wide distribution. PMID- 2898254 TI - Thallium scintigraphy in patients with angina at rest. AB - Sixty six patients with angina at rest were investigated by exercise electrocardiography, thallium scintigraphy, and coronary arteriography. A positive exercise electrocardiogram was highly predictive (93%) but poorly sensitive (52%) of coronary artery disease (greater than or equal to 50% stenosis). Thallium scintigraphy was as predictive of the presence of coronary artery disease (91%) but was also highly sensitive (91%). The diagnostic contribution of the thallium scan was greatest in those patients with an inconclusive exercise electrocardiogram without Q waves. PMID- 2898255 TI - Absence of excess peripheral muscle fatigue during beta-adrenoceptor blockade. AB - 1. In eight normal volunteers, the adductor pollicis (AP) was fatigued using intermittent trains of programmed, supramaximal stimulation at 1, 10, 20, 50, 100 and 1 Hz. Activity protocols were performed both with and without circulatory occlusion, both without and during propranolol 80 mg thrice daily in order to investigate the effects of beta-adrenoceptor blockade on 'peripheral' fatigue mechanisms. 2. The degree of beta-adrenoceptor blockade was assessed by the reduction of exercise tachycardia during cycle ergometry, e.g. pulse rates at 210 watts were reduced from 190 +/- 15 to 127 +/- 5 beats min-1 (mean +/- 1 s.d.) indicating that beta-adrenoceptor blockade was substantial and highly significant (P less than 0.001). 3. Before, during and following fatiguing activity with circulatory occlusion force declines were identical during and without beta adrenoceptor blockade. During and following activity without occlusion, there were slight declines in force which were questionably significantly different at 20 Hz (P less than 0.05). 4. The compound muscle action potential (CMAP) amplitude, measured from the skin surface over the muscle, was unaltered by beta adrenoceptor blockade before, during or after activity whether with or without circulatory occlusion. 5. The maximal relaxation rate (MRR) was not significantly reduced in previously unfatigued muscle during beta-adrenoceptor blockade. During activity, both with and without circulatory occlusion, there was no evidence that MRR was reduced significantly more during beta-adrenoceptor blockade. 6. The absence of a convincing effect of beta-adrenoceptor blockade on peripheral fatigue mechanisms may indicate that central mechanisms are involved or that impairments of peripheral force production, of a specific nature or as a result of exacerbation of limitations of circulatory oxygen transport, though small are detected during voluntary exercise and give rise to increases in motor unit recruitment and/or firing rates, and hence increased perception of fatigue. PMID- 2898256 TI - Effects of the beta 2-adrenoceptor antagonist ICI 118,551 on blood pressure in hypertensive patients known to respond to beta 1-adrenoceptor antagonists. AB - 1. The selective beta 2-adrenoceptor antagonist ICI 118,551, 50 mg orally given thrice daily, did not lower blood pressure in hypertensive patients known to respond to therapy with atenolol or propranolol. 2. This dosage regimen resulted in a small decrease in supine heart rate which might represent partial beta 1 adrenoceptor antagonism by ICI 118,551. 3. The results suggest that beta 2 selective antagonism does not play a role in the hypotensive action of beta adrenoceptor antagonists. PMID- 2898257 TI - Topographical distribution of prostaglandin E receptors in human myometrium. AB - The binding of radiolabelled prostaglandin (PG) F2 alpha and PGE2 by human myometrium was measured in vitro and the distribution and characteristics of the binding sites in non-pregnant and pregnant uteri were studied. PGF2 alpha binding sites were of low affinity (Kd 30 nM) and could be occupied by PG of the E series with higher affinity than PGF2 alpha itself. PGE binding sites were of high affinity (Kd 1.5 nM) and highly specific for PG of the E series, suggesting that they represent true PGE receptors. The concentration of PGE receptors was higher in non-pregnant than in pregnant uteri at term. In non-pregnant uteri the concentration of PGE receptors was highest in the fundus and decreased towards the cervix; in term pregnant uteri the concentration was constant in all areas. In both non-pregnant and pregnant uteri there was a significantly lower PGE binding affinity in cervix than in myometrium from the fundus-corpus area. The concentrations and affinity of PGE receptors were similar during the proliferative and secretory phases of the menstrual cycle and were not influenced by age of the patient. PGE receptors were not influenced by the presence or absence of primary dysmenorrhoea but appeared to be increased in unexplained menorrhagia. PMID- 2898258 TI - Stereochemistry and accessibility of prosthetic groups in flavoproteins. AB - Using 8-demethyl-8-hydroxy-5-deaza-5-carba analogues of the appropriate flavin nucleotides, we determined the stereochemistry of interaction between coenzyme and substrate for several flavoproteins. The enzymes were D-amino acid oxidase, L lactate oxidase, and D-lactate dehydrogenase, all three of which interact with pyruvate, as well as cyclohexanone monooxygenase and 2-methyl-3-hydroxypyridine-5 carboxylic acid oxygenase, which were both probed with nicotinamide nucleotides. L-Lactate oxidase and D-lactate dehydrogenase used the si face of the modified flavin ring while the other three enzymes showed re-side specificity. This selection of flavoenzymes includes FAD- and FMN-dependent enzymes, enzymes that follow a carbanion mechanism, and others that have hydride transfer as an integral part of their reaction pathway. PMID- 2898259 TI - A new kinetic approach for studying phospholipase C (Clostridium perfringens alpha toxin) activity on phospholipid monolayers. AB - The enzymatic activity of purified phospholipase C (alpha toxin) from Clostridium perfringens was investigated with various phospholipid monolayers. A two-step reaction was used. Enzymatic hydrolysis of insoluble lecithin films by phospholipase C, generating 1,2-diacylglycerol and water-soluble phosphocholine, was coupled with the action of pancreatic lipase in order to give rise to fatty acid and 2-monoacylglycerol, which are rapidly desorbed from the interface. With this new procedure, it is possible to obtain continuous and accurate kinetic measurements of the phospholipase C catalyzed reaction with phospholipid monolayers as the substrate. It is thus possible to avoid the use of radiolabeled substrates as necessary in previous studies, and the difficulties caused by diacylglycerol accumulation in the lipid film are minimized. No hydrolysis was detected when either phosphatidylethanolamine, phosphatidylserine, or phosphatidylglycerol films were used as substrates. By means of a film transfer technique, Ca2+ and Zn2+ ions were found to play a specific and critical role. The present study demonstrates clearly for the first time that Ca2+ is essential for enzyme binding to lipid films, whereas Zn2+ is specifically involved in the catalytic hydrolysis of the substrate. PMID- 2898260 TI - Glutathione-mediated transport across intestinal brush-border membranes. AB - Glutathione transport was studied in brush-border membrane vesicles of rabbit small intestine in which gamma-glutamyl transpeptidase (EC 2.3.2.2) had been inactivated by a specific affinity-labeling reagent, L-(alpha S,5S)-alpha-amino-3 chloro-4,5-dihydro-5-isoxazoleacetic acid (AT125). Transport of intact [glycine-2 3H]GSH occurred into an osmotically active intravesicular space of AT125-treated membranes. The 0.1 M NaSCN gradient (Na+ inside greater than Na+ outside) in the transport medium could be replaced with KSCN or NaCl without affecting transport activity. The initial rate of GSH transport followed Michaelis-Menten saturation kinetics (Km = 17 microM). The results suggest that, in these membranes, there was an Na+-independent mediated transport for intact GSH with marked specificity and affinity. In fact glycine, glutamic acid and cysteine did not decrease GSH uptake, as was also true for glycylglycine and glycylglycylglycine; only gamma glutamylcysteinylglycyl ester, a derivative of GSH, partially inhibited GSH transport. PMID- 2898261 TI - Rapid stimulation of liver palmitoyl-CoA synthetase, carnitine palmitoyltransferase and glycerophosphate acyltransferase compared to peroxisomal beta-oxidation and palmitoyl-CoA hydrolase in rats fed high-fat diets. AB - Key enzymes involved in oxidation and esterification of long-chain fatty acids were investigated in male rats fed different types and amounts of oil in their diet. A diet with 20% (w/w) fish oil, partially hydrogenated fish oil (PHFO) and partially hydrogenated soybean oil (PHSO) was shown to stimulate the mitochondrial and microsomal palmitoyl-CoA synthetase activity (EC 6.2.1.3) compared to soybean oil-fed animals after 1 week of feeding. Rapeseed oil had no effect. Partially hydrogenated oils in the diet resulted in significantly higher levels of mitochondrial glycerophosphate acyltransferase compared to unhydrogenated oils in the diet. Rats fed 20% (w/w) rapeseed oil had a decreased activity of this mitochondrial enzyme, whereas the microsomal glycerophosphate acyltransferase activity was stimulated to a comparable extent with 20% (w/w) rapeseed oil, fish oil or PHFO in the diet. Increasing the amount of PHFO (from 5 to 25% (w/w)) in the diet for 3 days led to increased mitochondrial and microsomal palmitoyl-CoA synthetase and microsomal glycerophosphate acyltransferase activities with 5% of this oil in the diet. The mitochondrial glycerophosphate acyltransferase was only marginally affected by increasing the oil dose. Administration of 20% (w/w) PHFO increased rapidly the mitochondrial and microsomal palmitoyl-CoA synthetase, carnitine palmitoyltransferase and microsomal glycerophosphate acyltransferase activities almost to their maximum value within 36 h. In contrast, the glycerophosphate acyltransferase and palmitoyl-CoA hydrolase (EC 3.1.2.2) activities of the mitochondrial fraction and the peroxisomal beta-oxidation reached their maximum activities after administration of the dietary oil for 6.5 days. This sequence of enzyme changes (a) is in accordance with the proposal that an increased cellular level of long chain acyl-CoA species act as metabolic messages for induction of peroxisomal beta-oxidation and palmitoyl-CoA hydrolase, i.e., these enzymes are regulated by a substrate-induced mechanism, and (b) indicates that, with PHFO, a greater part of the activated fatty acids are directed from triacylglycerol esterification and hydrolysis towards oxidation in the mitochondria. It is also conceivable that the mitochondrial beta-oxidation is proceeding before the enhancement of peroxisomal beta-oxidation. PMID- 2898262 TI - Expression of the cytosolic and particulate forms of transglutaminase during chemically induced rat liver carcinogenesis. AB - Transglutaminase (EC 2.3.2.13) activity in chemically induced rat hepatocellular carcinomas was reduced by some 65% when compared to normal rat livers. The majority of the remaining activity (approx. 85%) was found in the particulate fraction. The use of non-ionic detergent to extract the transglutaminase activity present in both normal and tumour tissue followed by its separation on a Mono-Q column revealed two distinct peaks of activity. These peaks of activity were equivalent to those previously identified as a membrane-bound transglutaminase and the more characteristic cytosolic or tissue transglutaminase. The ratio of the activity of the cytosolic enzyme to that of the membrane-bound enzyme in normal liver was calculated as 5:1. In hepatocellular carcinomas, this ratio was reduced to 0.4:1. No significant change in the activity of the membrane-bound enzyme was detectable in tumour tissue. Comparison of the cytosolic enzyme found in hepatocellular carcinomas with that found in normal liver indicated no change in its molecular weight, Km,app for putrescine incorporation into N,N' dimethylcasein and sensitivity to activation by Ca2+. These observations suggest that the reduction in transglutaminase activity observed in the hepatocellular carcinoma is due to a selective reduction in the expression of the cytosolic transglutaminase. PMID- 2898263 TI - [Action of trimethyl 3,3-N-hexene-5-lactam on the mechanical properties of the longitudinal fibers of the rat colon. An in vitro study]. AB - The effects of trimethyl 3,3-N-hexene-5-lactam (T. H. L.) on the mechanical properties of longitudinal muscle strips of the distal rat colon were investigated through stretching, electrical stimulation and addition of pharmacologic agents. T. H. L. abolished the contraction induced by electrical stimulation and decreased amplitude of contractions induced by carbamoylcholine and serotonin. It further reduced the relaxation induced by adrenaline. PMID- 2898264 TI - [Enzyme systems of the substrate and cofactor supply of hyperlipogenesis in non insulin-dependent diabetes]. AB - Enzymatic systems of hepatic hyperlipogenesis supply by substrate (acetyl-CoA) and cofactors (NADPH and ATP) were studied in experiments on diabetic C57Bl/Ks J mice (db/db) that served as a model of non-insulin dependent diabetes. The rise in acetyl-CoA synthetase activity catalyzing the primary step of lipogenesis from acetate has been found, while pyruvate dehydrogenase complex activity did not differ from the control and ATP-citrate lyase activity was lowered. Hyperlipogenesis in non-insulin dependent diabetes was induced by the activation of cellular energy supply revealed in enhanced 2-oxoglutarate dehydrogenase activity and elevated ATP level, as well as changes in the activity ratio of NADPH supply and utilization and the rise in fructose-1,6-diphosphate, allosteric effector of fatty acid synthetase, which resulted in the increase of the enzyme activity and created wider potentials of NADPH utilization as a reducing equivalent in lipogenesis. PMID- 2898265 TI - [Restriction fragment length polymorphism of c-fos and c-src oncogene loci in spontaneously hypertensive (SHR) and control (WKY) rats]. AB - Interstrain restriction fragments length polymorphism (RFLP) was detected after Southern blot hybridization of DNA from spontaneously hypertensive rats (SHR) and WKY rats treated with Bam HI restrictase with c-fos probe. The SHR genome is characterized by an additional miner band of 4.0 kilobase. RFLP was also revealed in c-src locus by Eco RI and Hind III restrictases. The major characteristic bands are 1.6 kb (SHR) and 2.4 kb (WKY) after Eco RI restriction and 3.4 kb (SHR) and 4.1 kb (WKY) after Hind III restriction. These RFLP can be used as mendelian traits in the linkage studies of distribution of blood pressure and other quantitative physiological traits in (SHR x WKY) F2 hybrids. The interstrain polymorphism determined in c-fos and c-src can also appear important in the evaluation of their physiological role in the cell. PMID- 2898267 TI - Management of unstable angina soon after myocardial infarction. AB - The recurrence of angina soon after myocardial infarction is not uncommon and represents areas of viable myocardium at risk from infarct extension and thus a worse prognosis. A better understanding of the pathogenesis of acute ischaemic syndromes and developments in interventional cardiology in the past decade have helped us rationalize our approach to this high-risk subset and achieve maximal myocardial salvage with its short- and long-term benefits. PMID- 2898266 TI - Distribution of somatostatin receptors on murine spleen and Peyer's patch T and B lymphocytes. AB - Recent evidence suggests that the neuropeptide somatostatin (SOM) plays an immunoregulatory role. We demonstrated previously that SOM inhibits concanavalin A-induced cell proliferation and immunoglobulin synthesis by murine Peyer's patch and splenic lymphocytes. Available data suggest that these effects are in part mediated by specific SOM receptors expressed by lymphocytes, but as yet these receptors have not been characterized. Using cytofluorimetry we investigated the distribution and specificity of binding of fluorescent SOM (SOM*) to murine Peyer's patch and splenic T- and B-lymphocyte subpopulations. The specificity of binding was confirmed by radioassay. T and B cells from both organs showed specific binding of SOM*. In Peyer's patches, approximately 50% of all cell populations studied (whole, T- and B-cell-enriched) bound SOM specifically and this was significantly higher than the corresponding splenic lymphocyte populations. Eighty to eighty-four percent of Peyer's patch Thy1.2+, Lyt1+, or L3T4+ cells and 94% of Lyt2+ cells bound SOM. Greater than 80% of B cells from this organ bound SOM (sIgA+ = sIgM+ greater than sIgG+ cells). In spleen, approximately 30% of Thy1.2+, Lyt1+, or L3T4+ cells bound SOM and this was significantly less than the proportion of Lyt2+ cells (53%) which did so. More sIgA+ (89%) than sIgG+ (66%) than sIgM+ (55%) B cells bound SOM*. Although we have previously shown that the effect of SOM on immunoglobulin synthesis was relatively isotype-specific (IgA synthesis was predominantly affected, especially in Peyer's patches) this cannot be explained solely on the basis of preferential expression of SOM receptors by distinct lymphocyte subsets. Instead, it is probably the result of the specific immunological microenvironment in which the lymphocytes reside. PMID- 2898268 TI - Weight loss in obese subjects on a restricted diet given BRL 26830A, a new atypical beta adrenoceptor agonist. AB - A double blind placebo controlled study was carried out in 40 subjects newly referred for treatment for obesity to determine the effects of the new thermogenic beta adrenoceptor agonist BRL 26830A. The subjects were randomised to receive either BRL 26830A, 200 mg daily for two weeks then 400 mg daily, or placebo for 18 weeks, and all were instructed to follow a 3.35 MJ diet that was low in fat and high in fibre. Weight loss was 15.4 (SD 6.6) kg in subjects given BRL 26830A compared with 10.0 (5.9) kg in those given placebo (p = 0.02). The relative weight loss was 0.93 (0.39%) a week with BRL 26830A and 0.61 (0.38)% with placebo (p = 0.02). Urinary excretion of nitrogen was similar in both groups, whereas measurements of skinfold thickness indicated a 4.1 kg difference in the amount of fat lost, suggesting that weight loss with BRL 26830A was mainly from adipose and not lean tissue. BRL 26830A had no effect on resting pulse rate or pressor effects on either diastolic or systolic blood pressure. No significant differences were found between the two groups in serum cholesterol concentration, percentage of high density lipoprotein cholesterol, plasma concentrations of glucose and insulin, the ratio of glucose to insulin, serum concentrations of triiodothyronine and thyroxine, and creatinine clearance. Short term administration of BRL 26830A to six subjects who had taken the drug for 18 weeks showed that the expenditure of energy increased by 11.6% during the second hour after administration, which suggests that BRL 26830A may enhance weight loss thermogenically. BRL 26830A may be a useful drug in the treatment of obesity. PMID- 2898269 TI - Lithium increases dynorphin A(1-8) and prodynorphin mRNA levels in the basal ganglia of rats. AB - The aim of this study was to understand the possible influence of the antimanic drug, lithium, and the neuroleptic, haloperidol, alone or in combination, on the regulation of dynorphin biosynthesis in the striatum. The study was done using male Fisher-344 rats subjected to a regimen of subchronic administration of lithium chloride (4 mEq/kg/day for 1,2,4 or 6 days, i.p.) or a regimen of chronic oral administration of a diet containing lithium carbonate (1.5 g/kg of the diet). Subchronic administration of lithium increased striatal dynorphin A(1-8) like immunoreactivity (DN-LI) in a time-related fashion. Immunocytochemistry revealed an increase in DN-LI in fibers and cells clustered in 'patches' throughout striatum. The increase in DN-LI was reversible on cessation of lithium administration. Concurrent administration of lithium and an opiate antagonist, naltrexone, or a dopamine receptor antagonist, haloperidol, did not influence the changes induced by lithium. Chronic oral administration of lithium for 21 days led to an increase in DN-LI in the striatum. Co-administration of haloperidol with the 21 day regimen of lithium administration failed to affect the increase in DN-LI. The prodynorphin mRNA abundance in the striatum was quantitated by a molecular hybridization procedure using a prodynorphin 32P-cRNA probe generated from the Riboprobe system. Evidence from the Northern blot analysis reveals that lithium increases the prodynorphin mRNA abundance in the striatum. These results indicate that lithium affects the dynamics of prodynorphin biosynthesis in the striatum, presumably increasing transcription and/or translational processes. PMID- 2898270 TI - A cholinergic antagonist blocks cold stress-induced alterations in rat adrenal tyrosine hydroxylase mRNA. AB - The role of nicotinic cholinergic transmission in cold stress-induced alterations in rat adrenomedullary tyrosine hydroxylase (TH) mRNA was investigated by RNA dot blot hybridization, using a cloned TH cDNA probe. Chlorisondamine, a ganglionic blocking agent, greatly attenuated the induction of TH mRNA levels caused by cold exposure, whereas carbachol and nicotine, cholinergic agonists, increased TH mRNA in control animals. These results suggest that cholinergic nicotinic receptors play a key role in the transsynaptic induction of adrenal TH gene expression. PMID- 2898271 TI - Substance K (NKA) increases tyrosine hydroxylase mRNA in cultured substantia nigra. AB - Cultured explants of the mouse substantia nigra were used to analyze mechanisms underlying the depolarization-induced increase in tyrosine hydroxylase activity. Steady-state levels of messenger RNA encoding tyrosine hydroxylase were detected using an antisense riboprobe in an RNase protection assay. Explants exposed to the depolarizing agent, veratridine, exhibited an approximate 2-fold increase in tyrosine hydroxylase messenger RNA. Moreover, the native presynaptic excitatory agonist substance K also elicited a significant increase in tyrosine hydroxylase message. We conclude that depolarizing influences induce tyrosine hydroxylase in the cultured substantia nigra in association with an elevation of enzyme messenger RNA. PMID- 2898272 TI - Brain neurotransmitter systems mediating behavioral deficits produced by inescapable shock treatment in rats. AB - The effect of inescapable footshock (IS) upon rats' motor activity (the open field and forced swim tests) was studied in rats subjected to drugs, and neurotoxin treatments, affecting their central neurotransmitter systems. The agonists of GABA-receptor complex, dopamine, noradrenaline and serotonin neuronal systems, as well as the cholinergic antagonist, partially reversed motor suppression induced by IS, while the dopamine agonist, chlorpromazine, and the cholinergic antagonist, physostigmine, potentiated it. The effects of chemical lesions of the brain monoaminergic neurons with p-chlorophenylalanine (pCPA), N chloro-ethyl-2,2-bromo-benzylamine (DSP-4), 6-hydroxydopamine (6-OHDA) and 5,7 dihydroxytryptamine (5,7-DHT) were more complex, depending upon the extent of monoamine depletion, and the kind of test applied. It is concluded that a decrease in the brain noradrenergic, serotonergic, dopaminergic and GABAergic neuronal activity, as well as the central cholinergic hyperactivity, might contribute to the behavioral suppression after IS. Thus the central mechanisms of behavioral deficits produced by IS involve multiple neurotransmitter systems, and the analysis of their role in more complicated behavioral patterns must also take into account changes in animals' baseline and stimulated motor activity. PMID- 2898273 TI - Orally administered MDMA causes a long-term depletion of serotonin in rat brain. AB - Recent studies suggest that 3,4-methylenedioxymethylamphetamine (MDMA), when administered subcutaneously, is toxic to central serotonergic neurons in rats. Because humans typically self-administer this drug orally, we compared this route to the s.c. route of administration. Orally administered MDMA produced a dose related depletion of serotonin comparable to that produced by the s.c. route. These findings suggest that MDMA, when given orally, retains it neurotoxic activity and that humans using MDMA may be at risk for developing a persistent depletion of brain serotonin. PMID- 2898274 TI - Immunocytochemical localization of somatostatin in the cerebral cortex of lizards. AB - The distribution of somatostatin-like immunoreactivity in the cerebral cortex of two lizards has been studied. Results are similar in both species. Somatostatin positive neurons show variable morphology; they are bipolar, multipolar or pyramidal cells. Their distribution within the cerebral cortex is not homogeneous: they tend to be found in the innermost cortical layer, the deep plexiform layer, where they constitute a constant population in the region of the dorsomedial cortex. All immunoreactive processes observed in the cerebral cortex belong to somatostatin cortical neurons since no immunoreactive fiber is found to reach or leave the telencephalic cortex. Most of the dendrites are smooth or sparsely spinous. Axons are abundant in the deep plexiform layer; in the dorsomedial cortex a prominent terminal field appears in the outermost region of the superficial plexiform layer, which may arise from the neuronal somatostatin immunoreactive population found deeper in the same cortex. PMID- 2898275 TI - In vitro release of somatostatin from cerebral cortical slices: characterization of electrically evoked release. AB - Calcium-dependent, tetrodotoxin (1 microM)-sensitive release of somatostatin-like immunoreactivity (SRIF-LI) could be evoked by electrical field stimulation of vibratome-cut cerebral cortical slices superfused in vitro. The release of SRIF LI from cortical slices was frequency-dependent, and showed facilitation between 5 and 25 Hz. Release was also current-dependent and above a threshold of 10 mA increased to plateau at 80 mA. Addition of peptidase inhibitors did not improve the recovery of SRIF-LI, and HPLC analysis of the released material showed that over 95% of SRIF-LI released corresponded to SRIF-14 (SRIF-28). PMID- 2898276 TI - The developmental appearance of Thy-1 in the avian cerebellum. AB - The cellular localization of the Thy-1 antigen during development of the chick cerebellum has been investigated using a monoclonal antibody SB1-20.11. Improved cellular morphology and retention of both membrane and intracellular antigenicity was achieved by the immunohistochemical labelling of polyester wax sections using an indirect peroxidase visualization protocol. A parallel histological investigation was carried out using a modified silver staining procedure based on that of Bodian. Immunoreactivity was found throughout development in the soma and dendritic tree of the Purkinje cell, in the internal granular layer, white matter and elements of the deep cerebellar nuclei. The antigen's expression closely correlates to the morphological maturation of Purkinje cell population. Furthermore, it appears to reflect the formation of glomeruli and the basket cell interaction with the Purkinje cell. An association of Thy-1 with climbing fibres, as reported previously in rodent species, cannot be unambiguously shown in the chick because of the high levels of Thy-1 expressed throughout development on the Purkinje cell dendrites in the molecular layer. The spatial and temporal pattern of expression in the chick cerebellum suggests that Thy-1 contributes to the definition of synaptic fields. PMID- 2898277 TI - Effect of depolarization on the maturation of cerebellar granule cells in culture. AB - The effect of depolarization on the maturation of granule cells derived from cerebella of 8-day-old rats can be studied in cultures in chemically defined media because their survival is not dependent on elevated K+ as it is when they are grown in serum-containing media. As an index of maturation, stimulus-coupled transmitter release was examined. This was chosen because it is closely associated with the neuronal phenotype and, in contrast to granule cells grown under depolarizing conditions in serum-containing media, it has not been known whether this property is expressed during the development of serum-free cells in culture. Veratrine-induced release of preloaded D-[3H]aspartate (Asp), an analogue of glutamate (Glu; the transmitter of the granule cells), was not detectable in the serum-free cells at a time (8-12 days in vitro) when this property was fully developed in cells grown in a medium containing serum and 25 mM K+ (reference cultures). This finding may be related to the failure of the expression of voltage-sensitive calcium channels in the serum-free granule cells. However, in comparison with reference cultures, voltage-sensitive 45Ca2+ entry was only transiently retarded in the serum-free cells. Furthermore, in contrast to the exogenous D-[3H]Asp, stimulated release of endogenous Glu was detectable, although it was substantially lower than in the reference cultures. Autoradiographic studies indicated that the failure to elicit evoked release of the exogenous amino acid was due to a severe retardation of the expression of the acidic amino acid carrier in the serum-free granule cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898280 TI - Methods to define and locate patterns of motifs in sequences. AB - A method to define and search for complex patterns of motifs in nucleic acid and protein sequences is described. With this method nucleic acid motifs can be defined in eight different ways and protein motifs in six. A pattern is defined by a list of motifs. The motifs in a list are combined using the logical operators AND, OR and NOT. The list also defines the ranges of allowed separations of the motifs in the pattern. Programs to search for patterns in individual sequences and libraries of sequences are described. Patterns are defined by users and stored as annotated disk files. Hence the programming to define and locate new structures can be performed by users and fewer specific novel algorithms should be required. Examples are given of searches for transcription initiation regions, nematode mitochondrial tRNA genes and for members of the globin sequence family. PMID- 2898278 TI - Neurotransmitters in the regulation of neuronal cytoarchitecture. AB - Recent experiments in isolated neurons in cell culture have demonstrated that neurotransmitters and associated electrical activity can directly affect neurite outgrowth. The results indicate that neurotransmitters have considerable potential to control the development of the neuronal circuits in which they participate in information coding in the adult. Cellular mechanisms regulating growth cone motility have been found to be similar to those regulating neurotransmitter release at the synapse and involve electrical activity, calcium and other second messengers. These similarities suggest that the morphological changes in connections observed in adult plasticity may involve the transition of synaptic terminals back to a growth mode. Excitatory and inhibitory neurotransmitters can interact to yield a net effect on neuronal morphology. In the intact nervous system a balance between these neurotransmitter inputs is probably important in maintaining circuits. Studies of neurotransmitter involvement in learning and memory processes indicate that brain function can alter brain structure and that neurotransmitters may control these structural changes. The hippocampus is one brain region in which we are beginning to define roles for neurotransmitters as sculptors of neuronal cytoarchitecture. The neurotransmitter glutamate was found to specifically affect the cytoarchitecture of hippocampal pyramidal neuron dendrites in a graded manner which suggests that glutamate may be involved in: establishing hippocampal circuitry during brain development; maintaining and modifying circuitry in the adult; and inducing neurodegeneration in several disorders including epilepsy, Alzheimer's disease, and stroke. Therapeutic approaches to disorders which affect brain cytoarchitecture may now be devised based upon knowledge of the neurotransmitters and their cellular mechanisms in the pertinent brain region. PMID- 2898279 TI - Convergence of thermal signals on the reticulospinal neurons in the midbrain, pons and medulla oblongata. AB - A total of 670 reticulospinal (RfS) and non-RfS neurons in the mesencephalic, pontile and medullary reticular formation (mRf, pRf and mdRf) were studied for the responsiveness to changes in temperatures of local brain sites, preoptic and anterior hypothalamus (PO/AH) and skin in the urethane anesthetized rat. Local thermoresponsiveness was found in 49.6% of 139 mRf neurons, 61.9% of 160 pRf neurons and 75.4% of 126 mdRf neurons. While the ventromedial region of pRf and mdRf contained predominantly warm-responsive neurons (54.8% and 62.5%), cold responsive neurons were much more frequently found in the mRf (33.8%) and the dorsolateral region of pRf (41.9%) and mdRf (50.0%). Responsiveness to hypothalamic temperature and/or skin temperature was observed in about 40-74% of Rf neurons. Higher incidence of responsiveness to remote temperatures was found among locally thermoresponsive neurons than among locally thermounresponsive neurons in all three areas. Particularly, there was a high degree of convergence of 'cold' signals from local and remote sites on the RfS neurons in the mRf and the dorsolateral pRf and mdRf. Microinjections of procaine and glutamate into these regions decreased and increased the cold-induced increase in EMG activity and shivering without any correlated changes in cardiovascular and respiratory parameters and pilomotor activity. The results suggest that RfS and non-RfS neurons in the mRf and the dorsolateral pRf and mdRf are involved in the control of thermoregulatory muscle tone and shivering. PMID- 2898281 TI - [Quantitative detection of serum free E-receptor and its clinical significance]. PMID- 2898282 TI - Cardiac effects produced by long-term stimulation of thoracic autonomic ganglia or nerves: implications for interneuronal interactions within the thoracic autonomic nervous system. AB - Electrical stimulation of an acutely decentralized stellate or middle cervical ganglion or cardiopulmonary nerve augments cardiac chronotropism or inotropism; as the stimulation continues there is a gradual reduction of this augmentation following the peak response, i.e., an inhibition of augmentation. The amount of this inhibition was found to be dependent upon the region of the heart investigated and the neural structure stimulated. The cardiac parameters which were augmented the most displayed the greatest inhibition. Maximum augmentation or inhibition occurred, in most instances, when 5-20 Hz stimuli were used. Inhibition of augmentation was overcome when the stimulation frequency was subsequently increased or following the administration of nicotine or tyramine, indicating that the inhibition was not primarily due to the lack of availability of noradrenaline in the nerve terminals of the efferent postganglionic sympathetic neurons. Furthermore, as infusions of isoproterenol or noradrenaline during the period of inhibition could still augment cardiac responses, whereas during the early peak responses they did not, the inhibition of augmentation does not appear to be due primarily to down regulation of cardiac myocyte beta adrenergic receptors. The inhibition was modified by hexamethonium but not by phentolamine or atropine. Inhibition occurred when all ipsilateral cardiopulmonary nerves connected with acutely decentralized middle cervical and stellate ganglia were stimulated, whereas significant inhibition did not occur when these nerves were stimulated after they had been disconnected from the ipsilateral decentralized ganglia. Taken together these data indicate that the inhibition of cardiac augmentation which occurs during relatively long-term stimulation of intrathoracic sympathetic neural elements is due in large part to nicotinic cholinergic synaptic mechanisms that lie primarily in the major thoracic autonomic ganglia. They also indicate that long-term stimulation in intrathoracic sympathetic neural elements with frequencies as low as 2 Hz may augment the heart as much as higher stimulation frequencies, depending upon the structure stimulated and the cardiovascular parameter monitored. PMID- 2898283 TI - Postnatal development of beta-adrenergic response in ventricular muscle of the rat heart. AB - In adult mammalian, heart responses to beta- and alpha-adrenergic stimulation are different: the beta-type effect exhibits a larger increase of relaxation than of contraction, while the alpha-stimulation has no selective influence on relaxation. The present results show that the effect of isoprenaline (ISO) on the neonatal rat heart during the 1st postnatal week is not a typical beta-effect in that the relaxant influence of beta-stimulation is lacking. During the 2nd and 3rd postnatal weeks the typical beta-response, with improved relaxation, gradually appears. The absence of the typical beta-effect is not caused by the lack of beta-receptors or cAMP-dependent phosphorylation reactions because in other respects, the positive inotropic effect of ISO is well developed at the moment of birth. In addition to these qualitative changes, also prominent quantitative changes occurred in the ISO response. The dose-response curves were shifted to the right with advancing age, suggesting reduced beta-agonist potency of the maturing tissue. The developed tension (Tmax) abruptly increased between the 12th and 17th postnatal days and then steeply declined during the next 2 weeks. Changes in Tmax correlated fairly well with the general ability of the tissue to generate extra force, as expressed by rest-dependent potentiation of twitch. However, during the 2nd postnatal week cardiac tissue seemed to be subsensitive to ISO, since all contractile parameters except T''max were depressed. The results suggest that the postnatal changes in beta-response are primarily determined by alternations in the electromechanical coupling process of the developing tissue, and less by the proper adrenergic mechanisms. PMID- 2898284 TI - Hypofrontality in schizophrenia. PMID- 2898285 TI - Reversible sellar enlargement due to growth hormone-releasing hormone production by pancreatic endocrine tumors in a acromegalic patient with multiple endocrine neoplasia type I syndrome. AB - A 28-year-old woman presented with hypoglycemia and acromegaly associated with pituitary sellar enlargement. Preoperative plasma levels of insulin and growth hormone (GH) were markedly elevated and there was mild hyperprolactinemia. Laboratory tests suggested hyperparathyroidism. Partial pancreatectomy was performed and two tumors were found. Morphologic examination revealed two well differentiated pancreatic endocrine neoplasms with distinct histologic, immunohistochemical, and ultrastructural features. Immunoreactivity for insulin was present in the larger tumor; the smaller tumor contained glucagon, gastrin, somatostatin, and pancreatic polypeptide. Both neoplasms demonstrated growth hormone-releasing hormone (GRH) immunopositivity and released GRH in vitro. Subsequent studies confirmed abnormally elevated preoperative plasma levels of GRH. Postoperatively, blood glucose, insulin, GRH, and GH normalized and there was regression of acromegalic features with significant reduction in sellar size. The clinicopathologic findings indicate that, in patients with multiple endocrine neoplasia type I (MEN-I), GRH production by pancreatic tumors can stimulate hypophysial somatotrophs resulting in GH excess and acromegaly due to a reversible pituitary lesion, most likely somatotroph hyperplasia. PMID- 2898286 TI - Chromosomal reorganization for the expression of recessive mutation of retinoblastoma susceptibility gene in the development of osteosarcoma. AB - Recent evidence indicates that the mutation of retinoblastoma susceptibility (RB) gene is also involved in the development of osteosarcoma. We studied 30 cases of osteosarcoma for the structural anomalies of the RB gene by Southern hybridization analysis with cDNA probes of the RB gene. Thirteen cases (43%) showed structural anomalies of the RB gene. They included the total or partial deletion, or rearrangement of the RB gene; seven with homozygous deletions and six with hemizygous deletions or rearrangements. By the use of restriction fragment length polymorphism fragments as chromosome markers, those seven tumors having homozygous deletions and four of six tumors having hemizygous anomalies showed the loss of heterozygosity at other loci on chromosome 13. Among those tumors with no apparent structural changes of the RB gene, seven cases showed the loss of heterozygosity on chromosome 13, and altogether the loss of heterozygosity by either homozygosity or hemizygosity was found in 18 (64%) of 28 informative cases. The loss of heterozygosity was also found for nine of 10 other chromosomes, of which chromosome 17 showed the highest frequency (77%). The tumors with loss of chromosome 13 alleles also showed additional losses of alleles on other chromosomes, while tumors retaining heterozygosity of chromosome 13 also retained heterozygosity at the informative loci on other chromosomes. Southern hybridization and karyotype analysis in some selected cases suggest that the concerted loss of heterozygosity at multiple loci may be a consequence of the polyploidization-segregation process. PMID- 2898287 TI - Mechanisms of multidrug resistance in HL60 cells: evidence that a surface membrane protein distinct from P-glycoprotein contributes to reduced cellular accumulation of drug. AB - HL60 cells exhibiting a 140-fold increase in resistance to vincristine contain three surface membrane proteins with molecular weights of 210,000 (P210), 180,000 (P180), and 150,000 (P150) which are highly phosphorylated in vivo and in an in vitro system in the presence of Mn2+ and [gamma-32P]ATP. These phosphorylated proteins are either absent or present in very low levels in membranes of drug sensitive cells. Growth of the vincristine-resistant isolate in the absence of drug results in a decrease in the level of resistance and a major reduction in the phosphorylation of P210 and P180. The phosphorylation of P150 is not altered in the revertant which still exhibits substantial levels of resistance. Further studies show that P210 and P180 are highly reactive with a monoclonal antibody against P-glycoprotein. These two proteins are present in only very low levels in revertant cells. The monoclonal antibody exhibits no reactivity with P150. In HL60 cells isolated for a 25-fold increase in vincristine resistance proteins reactive with P-glycoprotein monoclonal antibody are essentially absent. P150 is however highly phosphorylated in these cells. Additional experiments using lectin binding of 32P-labeled proteins demonstrates that P150 has properties distinct from P210 and P180. Analysis of drug uptake patterns in the vincristine-resistant isolates and the revertant shows that resistance is related to a reduced intracellular accumulation of drug. Reduced accumulation of vincristine is also found in HL60 cells isolated for resistance to Adriamycin. These cells are devoid of P-glycoprotein but contain phosphorylated P150. These results suggest that proteins P150, P180, and P210 may contribute to multidrug resistance in HL60 cells through a mechanism which involves reduced cellular accumulation of drug. P180 and P210 are structurally related whereas P150 is distinct from these two proteins. PMID- 2898288 TI - Multiple restriction fragment length polymorphisms of the human epidermal growth factor receptor gene. AB - We have examined the epidermal growth factor (EGF) receptor gene for structural alterations in fresh human tumors. DNA samples from 92 patients with solid tumors (lung cancer, 37; breast cancer, 24; head and neck cancer, 17; other tumors, 14) were analyzed and compared with those from 22 leukemia patients and 14 individuals without malignant neoplasms. When DNA samples were digested with HindIII restriction endonuclease, Southern blot analysis demonstrated 3 distinct polymorphic bands (9.8, 11, and 12 kilobases) after hybridization to the HER-A64 1 probe and another 2 distinct polymorphic bands (4.9 and 5.2 kilobases) after hybridization to the HER-A64-3 probe. Pedigree analysis of 43 members of a single family and comparative analysis of tumor and normal DNA samples from the same patients demonstrated that the variations in fragment size observed were due to 2 independent restriction fragment length polymorphisms in the region of the EGF receptor gene. Amplification of the EGF receptor gene was detected in 3 cases of breast cancer, but not in other tumors studied. We conclude that the human EGF receptor gene has multiple restriction fragment length polymorphisms and that in fresh human tumor samples rearrangement and amplification of the gene occur infrequently, if ever, within the region encompassed by the 2 complementary DNA probes used. PMID- 2898289 TI - Microtubule changes and cytotoxicity in leukemic cell lines treated with taxol. AB - Taxol, a diterpenoid plant product that enhances the polymerization of tubulin, is currently entering clinical trials in the treatment of human leukemia. In order to develop an in vitro assay to predict tumor sensitivity to taxol, human leukemic cell lines were exposed to clinically achievable concentrations of taxol for relevant exposure periods. Changes in microtubules visualized by indirect immunofluorescence were compared to drug sensitivity measured by a clonogenic assay. Taxol produced either multiple mitotic asters in G2/M or microtubule bundling throughout the cell cycle. In cells that were relatively resistant to taxol, microtubule bundling was reversible while microtubule bundling in relatively sensitive cells persisted in the presence or absence of taxol. In contrast, aster formation was unrelated to cytotoxicity in any cell line. In the future, these microtubule effects may be useful in predicting the chemotherapeutic efficacy of taxol. PMID- 2898290 TI - Note re: January 1, 1988 cover of Cancer Research. PMID- 2898291 TI - The role of biochemical mediators in peripheral nociception and bone pain. AB - There are various substances that mediate or modulate pain, but most of the studies have been in human skin or in laboratory animals. It is not known whether the same substances are involved in the pain of bone metastases, and the tentative conclusions made here are by extrapolation and by inference from the effects of drugs whose actions have been characterized. Prostaglandins E2 and I2 cause hyperalgesia to bradykinin and histamine, and they increase oedema formation. Other lipids may also have a similar potentiating role in pain and inflammation. Pain can be sensed from the periosteum, and from within the bone due to increased pressure. NSAIDs act mainly at peripheral sites to inhibit the formation of prostaglandins, and so lessen the hyperalgesia and oedema production, but a central inhibition of prostaglandin synthesis may also contribute to the analgesia. Opioid peptides have important roles in pain, mainly as analgesic substances, but in contrast some may have a role as algesic agents by an action on different receptors. The importance of these and other possible mediators and modulators of pain has not been fully assessed, but advances will be made when selective antagonists of lipoxygenases and kinins become available for use in humans. PMID- 2898292 TI - Localization of vasopressin-, vasoactive intestinal polypeptide-, peptide histidine isoleucine- and somatostatin-mRNA in rat suprachiasmatic nucleus. AB - Messenger RNAs (mRNA) coding for vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), somatostatin and vasopressin were localized in the suprachiasmatic nucleus (SCN) of the rat hypothalamus using in situ hybridization histochemistry. Specific mRNA coding for each of these peptides was distributed in areas coextensive with the immunohistochemical localization of the appropriate peptide. The autoradiographic signal produced with probes to VIP and PHI created dense concentrations of silver grains over neuronal perikarya in the ventrolateral SCN, and the coextensive distribution of both VIP- and PHI-mRNAs suggests that both peptides are synthesized within the same neurons. The distribution of somatostatin-mRNA was distinct from the of VIP and PHI. Labeled neurons are observed at the interface of the two SCN subdivisions and the distribution of these neurons is identical to those shown to contain somatostatin immunoreactivity. Vasopressin-mRNA is also differentially concentrated within neurons in the dorsomedial subdivision of the SCN in an area that is coextensive with vasopressin-immunoreactive perikarya. The discrete pattern of hybridization for each of these mRNAs indicates that each of these peptides are synthesized in SCN neurons and reaffirms the differential distribution of each of these chemically defined cell populations within cytoarchitecturally distinct subdivisions of the nucleus. PMID- 2898294 TI - Somatostatin-28- and somatostatin-14-like immunoreactivities in the rat pituitary gland. AB - Endogenous SS14- as well as SS28-like immunoreactive materials were detected in both male and female rats by radioimmunoassay and by immunocytochemistry on ultrathin frozen sections. The content of somatostatin-like immunoreactivity was 0.39 +/- 0.08 pg per mg adenohypophysis. Immunoreactivity was localized by immunocytochemistry in three pituitary cell types: somatotrophs, lactotrophs and thyrotrophs, but not in corticotrophs and gonadotrophs. In these three pituitary cell types the SS28- and the SS14-like immunoreactive materials were localized in the cytoplasm and in the nucleus. In the cytoplasm the immunoreactivity was seen in the cytoplasmic matrix and in the secretory granules. In the nucleus it was present mainly in the euchromatin close to the heterochromatin. In somatotrophs and lactotrophs, SS14- and SS28-like immunoreactive materials have been detected at the plasma membrane level. These results suggest that (1) endogenous SS14 and SS28 are present in adenohypophysis in somatotrophs, lactotrophs and thyrotrophs, and (2) the two peptides act on both the cytoplasmic components and the nucleus. PMID- 2898293 TI - Putative neurotransmitters in the retinae of three urodele species (Triturus alpestris, Salamandra salamandra, Pleurodeles waltli). AB - The immunocytochemical localization of several substances with putative neurotransmitter or modulator properties was investigated in the retinae of three urodele species. Gamma-aminobutyric acid-like immunoreactive labelling appeared in different types of amacrine and horizontal cells. In addition, labelled fibres in the optic nerve were detected. It was not possible to determine whether these fibres were ganglion-cell axons or part of an efferent projection. Endogenous serotonin was found in several populations of amacrine cells including stratified and diffuse types. Glucagon-like immunoreactivity appeared in one bistratified amacrine cell type, and neurotensin-like immunoreactivity was detected in a single monostratified amacrine cell type. Metenkephalin-like-immunoreactive labelling was type. Metenkephalin-like-immunoreactive labelling was rare but found in several sublaminae of the inner plexiform layer. Thus each peptide-like immunoreactive cell type makes up a distinct and unique population of cells and probably has a special functional role in retinal processing. There are striking similarities in the peptide-like immunoreactive patterns of Triturus alpestris and Necturus maculosus whereas in Ambystomatidae the peptide-like-immunoreactive systems appear to be differently organized. This supports the hypothesis that Salamandridae and Proteidae are more closely related to each other than to the Ambystomatidae. PMID- 2898295 TI - Neuropeptide distribution in the cervico-thoracic paravertebral ganglia of the cat with particular reference to calcitonin gene-related peptide immunoreactivity. AB - Paraffin sections of cervical and upper thoracic paravertebral ganglia of the cat were investigated by immunohistochemistry using antisera directed against calcitonin gene-related peptide (CGRP). The relationships of CGRP-immunoreactive structures to those exhibiting immunoreactivity to antisera against other regulatory peptides and dopamine-beta-hydroxylase (DBH), respectively, were studied in consecutive sections. Singly scattered CGRP-immunoreactive neuronal perikarya were observed in the superior and middle cervical ganglia as well as in the stellate ganglion. These neurons also displayed immunoreactivity to vasoactive intestinal polypeptide (VIP), and some additionally exhibited faint substance-P immunoreactivity. DBH- and neuropeptide Y-immunoreactive ganglion cells were not identical with CGRP-immunoreactive neuronal cell bodies. According to the immunoreactive properties of varicosities, which abut on CGRP/VIP immunoreactive perikarya, three types of CGRP/VIP-immunoreactive ganglion cells could be distinguished: (1) CGRP/VIP-immunoreactive neurons being surrounded by somatostatin-immunoreactive nerve fibers, (2) neurons being approached by both DBH- and met-enkephalin-immunoreactive varicosities, and (3) neurons receiving both DBH- and neurotensin-immunoreactive fibers. The stellate and upper thoracic ganglia harbored clusters of intensely VIP-immunoreactive somata, which lacked CGRP-immunoreactivity. Fine somatostatin-immunoreactive and coarse CGRP immunoreactive fibers were distributed within these clusters, whereas patches of neurotensin-immunoreactive fibers were complementarily arranged. At all segmental levels investigated, a few postganglionic neurons were approached by both CGRP immunoreactive and substance P-immunoreactive varicosities, but lacked a VIP immunoreactive innervation. Therefore, CGRP/substance P-immunoreactive fiber baskets appeared rather to be of extraganglionic origin than to emerge from intraganglionic CGRP/VIP/SP neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898297 TI - [A study on the early diagnosis of epidemic hemorrhagic fever by ELISA for examining antigens in urine]. PMID- 2898296 TI - [The study on inapparent infection in the endemic areas of the wild and domestic rat types EHF in parts of north-east areas in China]. PMID- 2898298 TI - Disappearance of high-grade left anterior descending stenosis after revascularization. AB - Complete resolution of a high-grade left anterior descending (LAD) stenosis 6 months after revascularization with a left internal mammary artery (IMA) graft and the first reported case of spontaneous IMA graft spasm during repeat cardiac catheterization for continued atypical chest pain in the same patient are reported. Mechanisms involving regression of atherosclerosis and atypical spasm are briefly discussed. PMID- 2898299 TI - Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. AB - We have used transgenic mice that carry an activated c-neu oncogene driven by a mouse mammary tumor virus (MMTV) promoter to assess the stepwise progression of carcinogenesis in mammary epithelium. Unlike the stochastic occurrence of solitary mammary tumors in transgenic mice bearing the MMTV/c-myc or the MMTV/v Ha-ras oncogenes, transgenic mice uniformly expressing the MMTV/c-neu gene develop mammary adenocarcinomas that involve the entire epithelium in each gland. Because these tumors arise synchronously and are polyclonal in origin, expression of the activated c-neu oncogene appears to be sufficient to induce malignant transformation in this tissue in a single step. In contrast, expression of the c neu transgene in the parotid gland or epididymis leads to benign, bilateral epithelial hypertrophy and hyperplasia which does not progress to full malignant transformation during the observation period. These results indicate that the combination of activated oncogene and tissue context are major determinants of malignant progression and that expression of the activated form of c-neu in the mammary epithelium has particularly deleterious consequences. PMID- 2898300 TI - mec-3, a homeobox-containing gene that specifies differentiation of the touch receptor neurons in C. elegans. AB - The mec-3 gene is essential for proper differentiation of the set of six touch receptor neurons in C. elegans. In mutants lacking mec-3 activity, the touch receptors express none of their unique differentiated features and appear to be transformed into other types of neurons. We cloned the mec-3 gene by transposon tagging and showed that a mec-3 mutant can be rescued by germ line transformation using a 5.6 kb genomic DNA fragment. In a strain in which transforming mec-3 DNA is present in about 50 copies per haploid genome, additional cells express a mec 3-dependent phenotype. The putative coding sequence of mec-3 contains a homeobox, suggesting that the mec-3 protein specifies the expression of touch cell differentiation by binding to DNA and regulating transcription of genes that encode the differentiated features of these cells. PMID- 2898301 TI - Interleukin-1 stimulates diacylglycerol production in T lymphocytes by a novel mechanism. AB - We have investigated the biochemical mechanism by which interleukin-1 (IL-1) serves as a comitogen with agents that directly activate the antigen receptor in T lymphocytes. We have studied the human T cell line Jurkat, which can be stimulated to produce Interleukin-2 by treatment with antibodies that bind to the CD3-antigen receptor complex and hence represents a model system for T cell activation. Using highly purified, recombinant human IL-1, we show that IL-1 stimulates rapid diacylglycerol and phosphorylcholine production from phosphatidylcholine (PC) in the absence of phosphatidylinositol turnover in Jurkat cells. This effect is also observed in peripheral blood T cells and a murine T cell line. The EC50 for IL-1 was 28 fM, and PC hydrolysis was detectable within 5 sec at 37 degrees C. The murine cell line had typical high-affinity IL-1 receptors (kd = 7 X 10(-11) M). However, we were unable to detect IL-1 binding to Jurkat cells. This reaction occurs via a novel mechanism and may explain the comitogenic activity of IL-1 in T lymphocyte activation as well as many of the pleiotropic biologic effects of this cytokine. PMID- 2898303 TI - [The ELISA technic in the screening of mosquitoes infected with Plasmodium falciparum]. PMID- 2898302 TI - The physiology of cerebral blood flow during cardiopulmonary resuscitation. PMID- 2898304 TI - gamma-Glutamyltranspeptidase-conferred resistance to hydroquinone induced GSH depletion and toxicity in isolated hepatocytes. AB - Hepatocyte resistance against glutathione (GSH) depleting xenobiotics was studied in an in vitro model. Hepatocytes were isolated from carcinogen treated rats that had received phenobarbital for three weeks. Isolated cells were incubated in GSH containing buffer with hydroquinone, which depleted GSH. Cells were then seeded on collagen coated plates and cultured overnight in complete medium. Attached cells were stained and the proportion of gamma-glutamyltranspeptidase (GGT) positive cells was counted. It was found that toxicity related to GSH depletion increased the proportion of GGT-positive cells from 10-15% up to 40-60%, indicating that the toxicity mainly affected GGT-negative cells. GSH added to the buffer was essential for this effect. It is concluded that GGT may protect GGT positive hepatocytes from GSH depletion and toxicity early during liver carcinogenesis. PMID- 2898305 TI - Effects of SO2 or NOx on toxic and genotoxic properties of chemical carcinogens. II. Short term in vivo studies. AB - Short term in vivo studies were performed to study biological effects of the common air pollutants SO2 or NOx and their influence on the genotoxic activities of nitrosamines. Hepatocytes and lung cells were isolated from Sprague-Dawley rats which had inhaled 50 p.p.m. of SO2 or NOx for 2 weeks. After incubating the cells for 1 h, genotoxicity was determined in hepatocytes by measuring DNA single strand breaks induced by N-nitroso-acetoxymethylmethylamine, N nitrosodimethylamine and N-nitrosomethylbenzylamine. Parameters of toxicity (trypan blue exclusion and leakage of serum enzymes) were determined in both liver and lung cells also following 1 h incubation. The activities of aryl hydrocarbon hydroxylase (AHH), nitrosodimethylamine demethylase (NDMA-D) and glutathione-S-transferase (GST) were determined in subcellular microsomal fractions isolated from lung and liver tissues. Finally, as a measure of overall toxicity, the activities of various serum enzymes were determined in the blood serum of the rats. It was found that the induction of DNA single-strand breaks by three nitrosamines was decreased in hepatocytes from SO2-treated animals. The viability of rat hepatocytes and of rat lung cells, as determined by trypan blue exclusion, was similar in all three treatment groups immediately after isolation, as well as after 1 h incubation with DMSO or with the nitrosamines. In contrast, the leakage of enzymes was different in hepatocytes of SO2-treated rats, since lactate dehydrogenase activity was decreased. Leakage of enzymes from the lung cells did not differ from group to group, but was lower than from hepatocytes. Foreign compound metabolizing enzymes were mainly decreased in NOx-treated animals, namely AHH, NDMA-D and GST in liver and GST in the lung. For SO2-treated animals NDMA-D was increased in liver and GST was decreased in lung. Blood serum enzyme levels were not greatly different from each other, except for lactate dehydrogenase which was elevated in SO2-exposed animals. PMID- 2898307 TI - Protection by beta-blocking agents against free radical-mediated sarcolemmal lipid peroxidation. AB - The effects of beta-blocking and class I antiarrhythmic agents on free radical mediated sarcolemmal lipid peroxidation were examined. Highly purified canine myocytic sarcolemmal membranes were pretreated with 10-800 microM of selected beta-blocking (propranolol, pindolol, metoprolol, atenolol, or sotalol) and class I (quinidine, lidocaine, procainamide, or diphenylhydantoin) antiarrhythmic agents at 37 degrees C for 10 minutes. Subsequently, a superoxide radical (derived from dihydroxyfumarate) driven, Fe3+-ADP catalyzed free radical generating system was added and incubated for up to 45 minutes. Lipid peroxidation of sarcolemma was determined by malondialdehyde formation. Pretreatment of the membranes with the five beta-blockers resulted in various degrees (20-95%) of inhibition of sarcolemmal peroxidation in a concentration- and time-dependent manner. All the class I agents were less effective (less than 20% inhibition). The order of potency of the beta-blockers was propranolol greater than pindolol greater than metoprolol greater than atenolol greater than sotalol and appeared to relate to their degree of lipophilicity. Propranolol, the most potent agent, achieved half-maximal inhibition of peroxidation at about 100 microM and achieved significance (p less than 0.01) at 20 microM. At pH 6.0, the efficacy of pindolol, metoprolol, atenolol, and sotalol diminished by 30-50% compared to pH 7.2, but the potency of propranolol remained unchanged. Since increased free radical production may occur during myocardial ischemia/reperfusion injury, the above findings suggest that the lipophilic beta blockers may provide additional antiperoxidative protection of ischemic tissue. PMID- 2898306 TI - Glutathione and glutathione-dependent enzymes in ovarian adenocarcinoma cell lines derived from a patient before and after the onset of drug resistance: intrinsic differences and cell cycle effects. AB - The regulation of glutathione and various glutathione-dependent enzymes has been studied in two ovarian adenocarcinoma cell lines derived from a patient before (PE01) and after (PE04) the onset of drug resistance to cis-platinum, chlorambucil and 5-fluorouracil. Reduced glutathione levels were higher in the drug resistant cells (PE04). This could possibly be attributed to a much higher (6.5-fold) gamma-glutamyl-transpeptidase activity. In addition, glutathione-S transferase (GST) and glutathione peroxidase were 2.9- and 2.3-fold higher in this cell line. Analysis of the GST subunit composition showed both cell lines contained high levels of the acidic GST and lower concentrations of a basic isozyme. The difference in GST activity between PE01 and PE04 did not appear to be related to the levels of these GST subunits. GSH, glutathione peroxidase and gamma-glutamylcysteinyl synthetase were all found to be regulated during the cell cycle, higher levels being detected in logarithmic versus confluent cultures of PE01 and PE04 and MCF7. This did affect some of the differences between PE01 and PE04 and therefore may be a contributing factor to the differential sensitivity of these cells to cytotoxic compounds. The above data provide the first evidence that tumour cells obtained from a patient before and after the onset of drug resistance have significant differences in glutathione-dependent enzyme content. PMID- 2898308 TI - gamma-Glutamyltransferase reference material: an example of international cooperation. AB - The different steps in the preparation of a certified reference material for gamma-glutamyltransferase are described. A preparation of pig kidney gamma glutamyltransferase, partly hydrolyzed with papain, was prepared and lyophilized in a matrix containing bovine serum albumin. The between-ampoule variability of gamma-glutamyltransferase was estimated to be 0.6%. The predicted degradation at 20 degrees C is 0.00% per year. The certification procedure involved 15 participating laboratories. The certified gamma-glutamyltransferase catalytic concentration of the reconstituted material, using the IFCC proposed method, is 86.8 U/1 with a 0.95 confidence interval of +/- 2.1 U/1. PMID- 2898309 TI - Early diagnosis of clostridial gas gangrene using sialidase antibodies. AB - In order to improve the diagnosis of gas gangrene, especially at an early stage of infection, new ways for the detection of the responsible Clostridia were investigated. Sialidase, known to be excreted in large amounts by the most frequently occurring myonecrotizing clostridial species, Clostridium perfringens, Clostridium septicum, and Clostridium sordellii, was isolated. With polyclonal antibodies raised against these enzymes, two immunological assays were established, which are directed against the sialidase activity (sialidase inhibition test) and the enzyme protein ('sandwich'-ELISA), respectively. Using these assays, species-specific information about the presence of clostridial sialidase was obtained within 50 min or 6 h. Animal tests revealed that both assays are applicable 8-12 h after clostridial infection, using resected tissues or wound fluids for estimations. The assays allow specific, sensitive, and quantitative measurement of clostridial sialidases, and no significant interference by sialidases from other microbes or from host tissues occurred. The applicability of the new assays for an early diagnosis of gas gangrene in human patients is discussed. PMID- 2898310 TI - Monoclonal antibodies to human kidney gamma-glutamyltransferase. AB - Eight hybridoma clones secreting large amounts of monoclonal antibodies against purified human kidney gamma-glutamyltransferase (GGT) were isolated and produced in ascites. None of them inhibits the catalytic activity of GGT. They all bind to the heavy subunit of this dimeric enzyme. Immunoblot analysis showed that these antibodies react with the catalytically active GGT. The monoclonal antibodies also recognize the heavy subunit of the human liver enzyme. This is of interest, as serum GGT is known to originate from the liver. None of the monoclonals reacts with GGTs from rat or pig kidney. After identification of epitopes specificities, the antibodies will be used for the development of immunoassays of GGT especially in human serum. PMID- 2898311 TI - Clinical assessment of beta blockade. AB - This study was undertaken to assess a clinical measurement (leg squats) in order to determine the adequacy of beta-adrenergic blockade (AdBB) utilizing the symptom-limited exercise test heart rate of less than 120 beats/min as the standard. Seventy subjects were tested, 35 receiving beta-adrenergic-blocking drugs in clinically determined maximal doses, and 35 subjects not receiving these agents. Sensitivity (Se), specificity (Sp), and positive (Pv+) and negative (Pv-) predictive values were calculated for post-leg squat heart rates of less than or equal to 100, less than or equal to 110 and less than or equal to 120 beats/min. Other variables analyzed for AdBB were resting heart rates and post-leg squat heart rate increase greater than 50% over baseline. A cost-benefit analysis was also performed. It was concluded that: (1) Neither the resting heart rate or percent increase in heart rate compared to baseline reliably predicted AdBB. (2) In patients receiving beta-blocking drugs, a post-squat heart rate of less than or equal to 100 beats/min had a Se = .82, Sp = .67, Pv+ .70, and Pv- .80, values not high enough to be reliably used in many clinical situations. (3) If the post squat heart rate was greater than 110 beats/min, however, AdBB is probably absent, since no subjects on beta blockers with maximum exercise test heart rate less than or equal to 120 beats/min had a post-leg squat heart rate greater than 110 beats/min. (4) For a reasonable range of cost and test performance estimates, utilization of the leg squat test as described here is favored on the basis of cost-benefit analysis. PMID- 2898312 TI - [HTLV-I associated myelopathy with multiple spotty areas found in the cerebral white matter and brain stem by MRI]. PMID- 2898313 TI - DNA polymorphism of the class II genes in DR4 cells. AB - The restriction fragment length polymorphisms of the DR-beta, DQ-alpha and -beta genes in 11 DR4 homozygous cells of different Dw type were investigated. The results showed that, with the enzyme-probe combination studied, the DR beta restriction polymorphism patterns were constant between the different cell lines. With the DQ alpha and DQ beta probes, variations in restriction patterns were obtained. No absolute correlation was seen between RFLP and Dw types. These differences may be useful in the investigation of the association between RA and specific subsets of DR4. PMID- 2898314 TI - New HLA DNA polymorphisms associated with rheumatoid arthritis. AB - Studies of restriction enzyme fragment length polymorphisms (RFLP) have further clarified two DNA polymorphisms detected in DR4 positive individuals with a DQ beta probe. These patterns have been designated DQ beta omega, characterized in the Dw4 homozygous typing cell (HTC) BM14 and DQ beta phi, characterized in the Dw4 HTC MCF, and so do not correspond with different Dw types. These patterns clearly segregate in families with HLA haplotypes. We suggest that omega and phi may be polymorphisms of the DX beta gene. The previously reported DX alpha polymorphisms U and L were found with all DR types and in association with DQ beta omega (U) and DQ beta phi(L). In addition DQ beta phi was found to be strongly associated with TA10 positively (a subdivision of DQw3) although this association was not absolute. Associations between RFLP and other HLA Class II and I antigens seen in DR4 patients and DR4 controls suggest the existence of at least two preferential allelic associations (PAA), one containing omega/U and the other phi/L. PAA1: DX alpha U-DQ beta omega-TA10 negative-DQw3-Dw4-DR4----Bw62 Bw6-Cw3-A2 PAA2: DX alpha L-DQ beta phi-TA10 positive-DQw3-Dw4-DR4----B44-Bw4-Cw3 A2 The frequency of the omega pattern was higher, although not significantly in the RA patients compared with controls. However, a significantly higher frequency of omega was found in RA patients with extra-articular manifestations (EA) compared (a) with controls (p less than 0.04) and (h) with those patients without EA (p less than 0.05). In addition the frequency of phi was significantly higher in RA patients with nodules and/or erosions (N/ER) compared with patients without these features (p less than 0.008). When cumulative scores were assigned to patients after assessing the number of components fulfilled for each PAA, PAA1 appeared to be pronounced in patients with EA and PAA2 in patients with N/ER. The frequency of a previously reported DQ beta T6 band found with the enzyme Taq 1 and DQ-beta probe was found at a higher frequency in RA patients compared with controls. In addition a significantly higher frequency of this band was found in female RA patients compared to males. PMID- 2898315 TI - Restriction fragment length polymorphism in Felty's syndrome. AB - Southern blot analysis with DR beta and DQ beta cDNA probes was used to compare genomic DNA from Felty's syndrome patients with HLA-DR-matched normal controls. We describe two restriction fragment length polymorphisms putatively associated with Felty's syndrome. PMID- 2898316 TI - The clinical applications of DNA polymorphisms. PMID- 2898317 TI - Detection of sequences that hybridize to human cytomegalovirus DNA in cervical neoplastic tissue. AB - Punch biopsies were taken from patients with cervical intraepithelial neoplasia and the DNA was extracted and examined for sequences which hybridized to human cytomegalovirus DNA by Southern blotting analysis. Two biopsies out of 43 were found to contain DNA which hybridized to human cytomegalovirus DNA. In one biopsy DNA sequences were detected which contained four restriction sites colinear with those of the prototype strain AD169. Evidence of rearranged viral DNA sequences was also found. PMID- 2898319 TI - Clinical evaluation of a new controlled-release formulation of naproxen in osteoarthritis and rheumatoid arthritis. Canadian Multicentre Study Group. AB - A two-part multi-centre study was carried out to assess the efficacy and tolerability of a new controlled-release (CR) naproxen tablet in the treatment of osteoarthritis and rheumatoid arthritis. Patients already receiving naproxen on a regular basis were first enrolled in a 6-week randomized double-blind trial comparing the controlled-release tablet (750 mg or 1000 mg once-a-day) to the standard marketed tablet (375 mg or 500 mg twice-a-day). At the end of this phase, patients in both treatment groups were eligible to enter the long-term phase involving 28 weeks of open-label treatment with controlled-release naproxen at the previously established dose level (750 mg or 1000 mg once-a-day). A total of 404 patients entered the initial double-blind phase, 320 of whom continued into the open-label phase. Twenty-nine (14%) naproxen patients and 23 (11%) naproxen CR patients were withdrawn prematurely from the double-blind phase, 87 (27%) patients from the open-label phase. Parameters of efficacy and tolerability were evaluated at base-line, during the double-blind phase (after 3 and 6 weeks of treatment), and during the open-label phase (after 20 and 34 weeks of treatment). The entire study population showed significant improvements in overall disease activity and severity of pain, but with no statistically or clinically significant differences between the two treatment groups; nor were there significant differences among treatments in incidence of adverse events. The patients treated with naproxen CR for an additional 28 weeks showed either no change or continued improvement in arthritic symptoms and no signs of toxicity. It was concluded that, in osteoarthritis and rheumatoid arthritis patients, once a-day controlled-release naproxen tablets can be substituted for standard naproxen tablets without loss of efficacy or tolerability. PMID- 2898318 TI - Detection of the mRNA to placental alkaline phosphatase by in vitro translation and immunoprecipitation. AB - RNA prepared from human placental syncytiotrophoblast tissue was analysed by in vitro translation and immunoprecipitation. The major polypeptide synthesized from syncytiotrophoblast mRNA was human placental lactogen, accounting for 15-20 per cent of the translated polypeptides. Immunoprecipitation using antibodies to placental alkaline phosphatase (PLAP) specifically precipitated polypeptides of 56 kD and 58 kD. The possible relationship between these polypeptides and those of placental microvillus PLAP is discussed. PMID- 2898320 TI - Controlled study on the anxiolytic activity of a newly-developed benzodiazepine, metaclazepam. AB - A double-blind, parallel group study was carried out in 50 patients with an anxiety disorder to compare the anxiolytic efficacy and tolerability of a recently developed benzodiazepine, metaclazepam, with that of bromazepam. Patients were allocated at random to receive treatment for 2 weeks with either 15 mg metaclazepam or 4 mg bromazepam per day in two divided doses. Assessments were made using the Hamilton anxiety rating scale (physician) on entry and after 7 and 13-days' treatment, and a visual analogue scale (patients) on entry and at the end of the study. The results showed that there was a significant, marked reduction in anxiety rating scores after 1 and 2 weeks in both groups and a significant improvement in the patients' subjective assessment of their condition after treatment. Few side-effects were reported in either group. PMID- 2898321 TI - A double-blind comparison of the anxiolytic activity of two benzodiazepines, metaclazepam and bromazepam, in anxiety neurosis. AB - A double-blind controlled trial was carried out in 50 patients with anxiety neuroses to compare the effectiveness of metaclazepam, a recently developed benzodiazepine with anxiolytic activity, and bromazepam. Patients were allocated at random to receive treatment for 13 days with either 15 mg metaclazepam or 4 mg bromazepam per day, in 2 divided doses. The patients' anxiety status was assessed on entry and after 7 and 13 days of treatment by the physician, using the Hamilton multi-factorial rating scale, and by the patients, using a self assessment rating scale. Both drugs produced a highly significant reduction in mean total scores, improvement being evident by the Day 7 assessment. Correlation between scores on the two scales was significant at all time points. Metaclazepam, however, was rated as producing a significantly greater improvement from baseline than with bromazepam on the self-rating scale. PMID- 2898322 TI - Ring calcification of coronary artery aneurysms. PMID- 2898323 TI - Delayed pleuropulmonary complications following coronary artery revascularization with the internal mammary artery. AB - We have seen four cases of delayed postoperative pleuro-pulmonary complications associated with use of the internal mammary artery (IMA) conduit. In each case the left IMA was used as a bypass conduit to the left anterior descending (LAD) coronary artery. In two of the instances the complications were life-threatening to the patients. Each patient was left with symptomatic residual roentgenographic changes. The IMA is becoming the graft of choice for coronary artery revascularization. The potential for delayed pleuropulmonary complications associated with use of this graft is not well recognized. PMID- 2898324 TI - Orthomolecular therapy: its history and applicability to psychiatric disorders. PMID- 2898325 TI - [Immune-mediated renal damage in epidemic hemorrhagic fever with renal syndrome (Hantavirus nephropathy]. PMID- 2898326 TI - [Transmission of epidemic hemorrhagic fever virus between mice and mites in EHF endemic areas]. PMID- 2898327 TI - Early neonatal drug utilization in preterm newborns in neonatal intensive care units. Italian Collaborative Group on Preterm Delivery. AB - The pattern of drug use in preterm newborns admitted to neonatal intensive care units (NICU) was monitored as part of a large multicenter study including a representative sample of Italian NICUs. All prescriptions from the admission of the mother through the 1st week of the neonate's life were carefully documented on standardized ad hoc forms, with particular attention to the timing and duration of each prescribed drug. The 706 babies included in the surveillance program received an average of 1.7 drugs during the early neonatal period, and were exposed to an average of 3.4 drugs over the whole perinatal period. The most commonly used drugs postnatally were vitamins, antibiotics (ampicillin, gentamicin and tobramycin), methylxanthines (aminophylline and caffeine), phenobarbital and furosemide. The frequency and intensity of the use of these drugs appears to be directly related to the severity of the clinical status, and inversely related to birth weight and gestational age. PMID- 2898328 TI - Metabolic activation of the halothane metabolite, [14C]2-chloro-1,1 difluoroethene, in hepatic microsomes. AB - Halothane is reduced to 2-chloro-1,1,1-trifluoroethane (CTE) and 2-chloro-1,1 difluoroethene (CDE) by cytochrome P-450. These compounds may potentially undergo secondary metabolism in vivo, but their capacity to undergo metabolic activation and bind to macromolecules is unknown. This study, therefore, compared the abilities of CDE and CTE to bind to microsomal components in relation to that of halothane in hepatic microsomes. The results show that CDE, in addition to halothane, binds to microsomes under conditions of cytochrome P-450 activity. While halothane bound predominantly to lipids under nitrogen, CDE bound mainly to protein under oxygen. No CTE binding under any conditions could be detected. On an equimolar basis, CDE binding to protein was approximately one-third of that of halothane under oxidative conditions, however, CDE binding was enhanced in the presence of halothane. The results support the hypothesis that CDE metabolism may contribute to the metabolic binding due to halothane exposures. PMID- 2898330 TI - Regiochemistry and substrate stereoselectivity of O-demethylation of verapamil in the presence of the microsomal fraction from rat and human liver. AB - The oxidative O-demethylation of verapamil (1), a calcium channel antagonist, in the presence of rat and human liver microsomes was examined. By using GC/MS methodology and synthesized regioisomeric standards, we showed that three of the four possible monophenolic metabolites, alpha-[3-([2-(3,4 dimethoxyphenyl)ethyl]methyl-amino) propyl]-3-methoxy-4-hydroxy-alpha-(1 methylethyl)phenyl-acetonitrile (2), alpha-[3-([2-(3,4-methoxyphenyl)ethyl]methyl amino) propyl]-3-hydroxy-4-methoxy-alpha-(1-methylethyl)phenylaceto nitrile (3), and alpha-[3-([2-(3-methoxy-4-hydroxyphenyl)ethyl]methylamino) propyl]-3,4 dimethoxy-alpha-(1-methylethyl)phenylacetonitrile (4) were formed. The other possible regioisomeric monophenolic metabolite 5 was not observed. Substrate stereoselectivity for the O-demethylation process was determined when pseudoracemic verapamil [equimolar (S)-(-)-verapamil-d6 and (R)-(+)-verapamil-d0] was used as substrate. In the presence of rat liver microsomes, significant substrate stereoselectivity was observed for formation of 4 (S/R ratio 2.28), whereas marginal substrate stereoselectivity was observed in the formation of both 3 and 2 (S/R ratio approximately 0.8). Substrate stereoselectivity for the O demethylation process in the presence of human liver microsomes was slight and variable (six samples). Quantitatively, the ratio of O-demethylation products obtained (4:2:3) was similar in the presence of rat and human liver microsomes. In both systems, more than one-half of the total O-demethylation occurred in the aromatic ring of the phenethylamine moiety, and of the total O-demethylation process, more para- than meta-O-demethylation was observed. The similarity of regioselectivity for O-demethylation in the presence of rat and human liver microsomes suggests a similar cytochrome P-450 isozyme or set of isozymes may be responsible for the O-demethylation process. PMID- 2898329 TI - Regioselective and stereoselective metabolisms of pyrene and 1-bromopyrene by rat liver microsomes and effects of enzyme inducers. AB - Due to the symmetrical property of pyrene (Py), trans-dihydrodiols formed at 4,5- and 9,10-positions are identical, as are the monohydroxylated products (phenols) formed at C1, C3, C6, and C8 positions. With a bromo substituent at C1 position of Py, 1-bromopyrene (1-BrPy) trans-4,5-dihydrodiol and 1-BrPy trans-9,10 dihydrodiol are distinctly different products, as are the phenolic products formed at C3, C6, and C8 positions. Products formed in the oxidative metabolism of 1-BrPy by rat liver microsomes were characterized by retention times on reversed-phase high performance liquid chromatography (HPLC), and by ultraviolet visible absorption and mass spectral analyses. We have compared regioselective and stereoselective metabolisms at the K- and non-K-regions of Py and 1-BrPy by liver microsomes from untreated (control), phenobarbital (PB)-treated, 3 methylcholanthrene (MC)-treated, and polychlorinated biphenyls (PCB, Aroclor 1254)-treated rats. The effects of inducers on the relative amounts of non-K region phenols formed in the metabolisms of Py and 1-BrPy by rat liver microsomes were: MC greater than PCB greater than PB greater than control. The relative order was PB greater than PCB greater than MC greater than control for the formation of both 1-BrPy trans-4,5-dihydrodiol and 1-BrPy trans-9,10-dihydrodiol in the metabolism of 1-BrPy. The ratios between metabolically formed 1-BrPy trans 4,5-dihydrodiol to Py trans-4,5-dihydrodiol, using 0.5 mg of microsomal protein per ml of incubation mixture, were between 0.4 and 0.6 in the presence of liver microsomes from untreated, PB-treated, and PCB-treated rats. However, the ratio was approximately 1.5 using liver microsomes from MC-treated rats. The ratios between the sum of 1-BrPy trans-9,10-dihydrodiol and 1-BrPy 9,10-epoxide to Py trans-9,10-dihydrodiol, and to 1-BrPy trans-4,5-dihydrodiol were in the range of 0.1 to 0.5 using four rat liver microsomal preparations. These data revealed the effects of a bromo substituent at C1 of Py on the regioselectivity of various rat liver microsomal enzymes toward the oxidative metabolism at various positions of 1-BrPy. The enantiomeric compositions of K-region dihydrodiols formed by four rat liver microsomal preparations were determined by chiral stationary phase HPLC and circular dichroism spectral analyses; the percentage of R,R-enantiomers were: Py trans-4,5-dihydrodiol, 78-79%; 1-BrPy trans-4,5-dihydrodiol, 74-77%; 1-BrPy trans 9,10-dihydrodiol, 86-97%. PMID- 2898331 TI - In vivo renal tubular secretion and metabolism of the disulfide of 2,3 dimercaptopropane-1-sulfonate. AB - The in vivo renal tubular secretion and metabolism of the disulfide of the heavy metal-complexing agent 2,3-dimercaptopropane-1-sulfonate (DMPS) was examined in the Sperber preparation. DMPS was readily oxidized to DMPS disulfide when incubated with chicken plasma, with whole blood or with urine in the presence of transition metals. Net reduction of the disulfide was not detected when the disulfide was incubated with chicken blood. When the disulfide was infused into the saphenous vein of chickens at a rate of 1 mumol of DMPS equivalents.min-1.kg of body weight-1, 62% of the DMPS disulfide that entered the renal portal circulation of the ipsilateral kidney was excreted in the urine unchanged during a single pass through the peritubular capillaries, 28% was excreted as DMPS, and 9% as an unidentified mixed disulfide. Net reduction of DMPS disulfide to DMPS occurred in vitro in rat kidney cytosol (pH 7.4) supplemented with 0.5 or 5.0 mM reduced glutathione. Reduction of DMPS disulfide to DMPS also occurred in EDTA Tris HCl (pH 9) containing glutathione disulfide and glutathione reductase. Intracellular reduction of DMPS disulfide to DMPS in the kidney, involving a glutathione-disulfide exchange reaction, may be important for the in vivo activity of DMPS as a complexing agent for mercury. PMID- 2898332 TI - The disposition of the hypolipidemic agent, o-(N-phthalimido)acetophenone, in Sprague-Dawley rats. AB - Disposition studies of the potent experimental hypolipidemic agent, o-(N phthalimido)acetophenone, were conducted in the laboratory rat. Intravenous administration of the drug demonstrated a declining biphasic plasma concentration time curve suggesting a rapid distribution into tissues. Less than 5% of the intravenous dose was recovered in urine and feces after 5 days. Oral administration of the drug showed that the maximum blood levels were attained within 15 min. After 48 hr, 92% of the orally administered 14C dose was eliminated either via urine (60%) or feces (40%). 14C in a 0-24-hr urine collection after oral administration showed that urinary radioactivity was composed of 22% of the parent compound o-(N-phthalimido) acetophenone, a benzoic acid metabolite (22%) o-(N-phthalimido)benzoic acid, and an amic acid metabolite (56%) N-(o-acetophenone)phthalamic acid. The two metabolites were unconjugated and possessed less hypolipidemic activity than the parent drug. PMID- 2898333 TI - Dose-dependent pharmacokinetics of recombinant tissue-type plasminogen activator in anesthetized dogs following intravenous infusion. AB - The pharmacokinetics of SK&F recombinant two-chain tissue-type plasminogen activator (tPA) following intravenous (iv) infusion were characterized in anesthetized, open chested mongrel dogs in which artificial intracoronary thrombi were formed. SK&F tPA was infused at rates of 0.5, 1, 2, 4, and 8 micrograms/kg/min (N = 3 to 5 per dose) for 90 min, and arterial blood samples were withdrawn during and after infusion for determination of functionally active tPA concentrations using a modified and validated S-2251 chromogenic assay. At all doses studied, steady state active tPA plasma concentrations were achieved 10 20 min after the onset of infusion. Upon cessation of infusion, active tPA plasma concentrations declined rapidly with a t1/2 of 2-3 min. The active tPA plasma concentration at steady state (Css) and the area under the tPA plasma concentration-time curve (AUC) increased linearly with the dose in the range of 0.5-4 micrograms/kg/min. However, as the dose was increased 2-fold from 4 to 8 micrograms/kg/min, the AUC and the Css increased 2.5-fold. The systemic clearance ranged from 15-16 ml/min/kg at doses of 0.5-4 micrograms/kg/min, but decreased to 11.7 ml/min/kg at the 8 micrograms/kg/min dose. With exceptions in three dogs, the volume of distribution at steady state approached or slightly exceeded the blood volume. Plasma tPA antigen concentrations were also determined in the dogs receiving the 2 micrograms/kg/min dose. At steady state, active tPA accounted for 40-60% of the total tPA antigen. The postinfusion t1/2 of the tPA antigen was considerably longer (13.46 +/- 5.94 min) than that of active tPA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898334 TI - Regioisomeric aromatic dihydroxylation of propranolol. Use of monohydroxylated intermediates for structural assignments of the metabolites formed in vitro. AB - The formation of dihydroxylated propranolol metabolites [(HO)2-Ps], determined as their trimethylsilyl derivatives, was investigated using GC/MS techniques. Tentative structural assignment for the (HO)2-Ps was achieved by matching retention times of the (HO)2-Ps arising from the incubation of synthetic mono-HO P regioisomers in the presence of the rat liver 9000g supernatant. Seven compounds were identified as (HO)2-Ps: 2,3-, 3,4-, 3,7-, 4,6-, 4,8-, 5,6-, and 7,8-(HO)2-P. Five of these regioisomers were observed as metabolites when propranolol was the substrate: 4,8-, 3,4-, 5,6-, and 4,6-(HO)2-P. The pathway for the formation of (HO)2-Ps was investigated by incubating propranolol in the presence of rat liver microsomes under an 18O2 atmosphere. 18O2 was the source of both hydroxyl group oxygen atoms indicating that sequential hydroxylation occurs. Mono-HO-Ps, not having hydroxyl groups at C-4 or C-5, proved to be the best substrates for the second hydroxylation. Propranolol is a better substrate than is 4-HO-P for formation of (HO)2-Ps. The regioselectivity of the second hydroxylation is predictable on the basis of expected sites of electrophilic substitution on the mono-HO-P intermediates. Substrate stereoselectivity in the formation of (HO)2-Ps was determined. PMID- 2898335 TI - Regioisomeric aromatic dihydroxylation of propranolol. Synthesis and identification of 4,6- and 4,8-dihydroxypropranolol as metabolites in the rat and in man. AB - The formation of the three prominent dihydroxylated propranolol [(HO)2-P] metabolites, 4,6-, 4,8-, and 3,4-(HO)2-Ps, was investigated in vivo in rat and in man. Authentic O,O-dibenzyl ethers of 4,6- and 4,8-(HO)2-P were synthesized from the corresponding dihydroxy-l-naphthaldehydes. The l-carboxyaldehyde group was used as the latent side chain l-naphthol ether available by Baeyer-Villiger oxidation and subsequent side chain elaboration. The benzyl ethers were cleaved, and the resulting dihydroxynaphthalenes were immediately derivatized with bis-N,O (trimethylsilyl)trifluoroacetamide. After ip administration of P-3,3-d2 (20 mg/kg) to rats, 4,6-, 5,6-, 3,7-, 3,4-, and 4,8-(HO)2-Ps were identified by GC/MS as urinary metabolites. After administering pseudoracemic propranolol [(2R)-P d0/(2S)-P-3,3-d2] ip to rats (20 mg/kg), parent ions of the (HO)2-Ps as trimethylsilyl derivatives were monitored by GC/MS. While 4,6- and 3,4-(HO)2-P arose stereoselectively from (2S)-propranolol, 4,8-, 4,7-, and 5,6-(HO)2-P arose stereoselectively from (2R)-propranolol. About 3.3% of the dose was converted to (HO)2-Ps. Three (HO)2-Ps, 4,6-, 4,8-, and 3,4-(HO)2-P, were identified as urinary metabolites of propranolol in man after a single oral dose of 80 mg of P-3,3-d2. Less than 1% of this dose was converted to urinary (HO)2-Ps in 24 hr. PMID- 2898336 TI - Regioisomeric products of propranolol metabolism. The monomethyl ethers of 3,4 dihydroxypropranolol and of 3,4-dihydroxypropranolol glycol. AB - Regioisomeric monomethyl ethers of the 3,4-catechol of propranolol (1) and its 3 aryloxypropane-1,2-diol (glycol) metabolite were prepared to prove the structures of these putative products of oxidative metabolism. The ring regioisomer 4 methoxy-3-hydroxypropranolol (3) was prepared from 1-acetoxy-3-acetyl-4 methoxynaphthalene (8). Baeyer-Villiger oxidation was the key step in converting the 3-acetyl functionality to the desired 3-naphthol. The ring regioisomer 4 hydroxy-3-methoxypropranolol (4) was prepared from 3-methoxy-1,4 dihydroxynaphthalene (13) by selective 1-O-acylation with trimethylacetyl chloride. 4-O-Benzylation, followed by hydrolysis, and side chain elaboration afforded the 4-O-benzyl ether of 4. Similar methods afforded glycols 5 and 6, with the side chain obtained by osmium tetroxide oxidation of an O-allyl group. GC/MS analysis using the trifluoroacetyl derivatives of these known standards showed both 3 and 4 were metabolites of 1 in the rat. From a single dose study in man, 4 was identified as a minor urinary metabolite, and both regioisomeric glycol metabolites 5 and 6 were observed. In addition, another regioisomeric hydroxymethoxyglycol metabolite was found. PMID- 2898337 TI - Relationship between the pharmacokinetic and pharmacodynamic profile of nilvadipine in the dog. AB - The purpose of this study was to determine the pharmacokinetic profile of nilvadipine and, using a chronic dog model, determine whether there was a correlation between plasma concentrations of the drug and hemodynamic effects. Nilvadipine was given to four dogs as single intravenous (iv) and oral doses. Pharmacokinetic parameters were estimated after each dose using model-independent methods. The mean elimination half-life was approximately 6 hr after both iv and oral doses. The absolute bioavailability of nilvadipine decreased from 67 to 27% after increasing oral doses (6 and 24 mg), probably because of reduced drug absorption from the gastrointestinal tract. Nilvadipine produced plasma concentration-related decreases in diastolic (DBP) and systolic (SBP) blood pressure and reflex increases in heart rate. The maximum reduction in DBP and SBP ranged from 34 to 53% and 17 to 47%, respectively, from control and was attained at about 0.1 and 0.7 hr after iv and oral doses, respectively. A strong linear correlation between the per cent reduction in both DBP (r = 0.9; p less than 0.001) and SBP (r = 0.66; p less than 0.001) and log plasma concentration of nilvadipine was established. The slopes of the concentration-response relationships were virtually superimposable after both iv and oral routes of administration. A plasma concentration of about 10 and 16 ng/ml was associated with a 14% reduction in DBP or SBP, respectively. There was no clear relationship between plasma concentrations of nilvadipine and changes in heart rate. PMID- 2898338 TI - Dose-dependent tissue uptake of flecainide during chronic administration in rabbits. AB - This study was designed to examine the metabolism of flecainide after repeated administration to rabbits. New Zealand White rabbits were administered either 7.5 mg/kg body weight (dose I) or 20 mg/kg body weight (dose II) flecainide twice daily intraperitoneally for 12-14 days. Serum, heart, liver, lung, kidney, muscle, fat, and brain were collected upon death. Flecainide concentrations in serum and tissues were determined by a liquid chromatographic procedure standardized in our laboratory. Serum and tissue flecainide concentrations showed a significant, dose-dependent increase after chronic administration. Flecainide accumulated in lung, liver, kidney, and heart, its concentration decreasing in that order. Tissue to serum flecainide ratios also followed a similar pattern. Cornea and urine contained flecainide metabolites which were not characterized. Only traces of flecainide were detected in brain and fat tissues. Substantial tissue uptake of flecainide should be considered in long term flecainide therapy. PMID- 2898339 TI - In vitro metabolism and covalent binding among ortho-substituted bromobenzenes of varying hepatotoxicity. AB - A series of ortho-substituted bromobenzene derivatives with widely differing hepatotoxicities were investigated for their tendency to undergo oxidative metabolism and protein covalent binding in the presence of rat liver microsomes in vitro. Compounds studied included o-bromobenzonitrile, o-dibromobenzene, bromobenzene, o-bromoanisole, and o-bromotoluene (names in order of decreasing hepatotoxicity and increasing rate of in vitro metabolism). No correlation was found between net covalent binding and toxicity. However, a good rank order correlation was observed between toxicity and the relative binding index of each compounds, defined as (picomoles covalently bound/nmol metabolized), with values ranging from a low of 7 with o-bromotoluene to a high of 365 with o bromobenzonitrile, Extensive side chain metabolism was observed with o bromotoluene (92-95%) and o-bromoanisole (26-42%), which accounts for their high rate of total metabolism and low relative binding index. The extent of tritium loss, relative to C-14, was assessed for each compound as an index of the "average oxidation state" of those metabolites, presumably epoxides and/or quinones, which covalently bound to protein. Tritium retention ranged from a high of 84% with o-bromobenzonitrile to a low of 21% with o-bromoanisole, and generally paralleled toxicity. These results show that introduction of ortho substituents onto bromobenzene leads to qualitative and quantitative changes in overall oxidative metabolism, as well as important qualitative changes in the nature of reactive metabolites formed. Nevertheless, the relative binding index computed for each compound appears to reconcile these changes to a large degree, giving an in vitro index which correlates well with toxicity. PMID- 2898340 TI - Effect of diet and gavage on the absorption and metabolism of fluperlapine in the rat. AB - Fluperlapine, Sandoz compound NB 106-689, 3-fluoro-6-(4-methyl-1-piperazinyl)-11H dibenz[b,e]azepine, in a 12-week toxicity study exhibited liver toxicity (moderate to severe hyperlipidosis) when administered to rats in the diet at 40 mg/kg/day and at 80 mg/kg/day, but not by gavage at 80 mg/kg/day. In order to elucidate those factors which might explain these differences in toxicological findings, the effect of mode of administration (diet vs. gavage) on the absorption and metabolism was investigated in rats. Although the peak concentration of radioactivity was earlier (2 hr vs. 15 hr) and higher (3.3 micrograms eq/ml vs. 1.6 micrograms eq/ml) by gavage than by diet, the extent of absorption based on AUC values and excretion of radioactivity was the same. Analysis of plasma and liver extracts for metabolites showed that although the metabolic pathways were the same after diet or gavage, the relative composition of drug and metabolites present was a function of the mode of administration. In the liver, the target organ, after multiple oral doses by the diet mode, 96% of the identified products represented hydroxylation; a minor amount of parent drug was present. After gavage, the drug (32%) and desmethylfluperlapine (25%) together accounted for 54% of the mixture, and hydroxylation accounted for 44%. In plasma after multiple oral doses, a similar trend was observed; there was a greater percentage of the hydroxylated metabolites compared to the nonhydroxylated metabolites after diet administration and an almost similar proportion of these products after gavage administration. It is possible that the observed differences in toxicity could be due to a difference in the exposure of the target organ to drug and metabolites. PMID- 2898341 TI - Disposition and metabolism of double-labeled [3H and 14C] N-methyl-2 pyrrolidinone in the rat. AB - The disposition of N-methyl-2-pyrrolidinone (NMP) was studied in the rat using tritium-labeled ([4-3H]NMP) and carbon-14-labeled ([methyl-14C]NMP and [ring 14C]NMP) radioisomers. Male Sprague-Dawley rats were administered a single intravenous dose (45 mg/kg) of 5.0 microCi of 3H or 14C for single-labeled disposition studies or 5.0 microCi of 3H and 2.5 microCi of 14C for double labeled studies (2:1 ratio, 3H:14C). Plasma levels of intact NMP were analyzed by HPLC through 6 hr after dosing and suggested a rapid distribution phase followed by a slow elimination phase. The half-life for the terminal elimination phase from plasma was about 7 hr for both 14C-isomers and 9.9 hr for the 3H-isomer. The major route of excretion of radioactivity was via the urine and accounted for about 70% of the dose within 12 hr. After 24 hr, cumulative excretion in urine represented about 80% of the dose. The 2:1 ratio of administered 3H:14C was maintained in urine through 6 hr. Measurement of radioactivity in tissues at 6 hr showed the liver and intestines to contain the highest accumulations of radioactivity, representing approximately 2% and 3% of the dose, respectively. Tissue distribution of radioactivity was similar for all three radiolabeled isomers and showed that NMP was extensively distributed to all major organs. Radiomonitored HPLC analyses of urine revealed the presence of one major and two minor metabolites. The major metabolite, representing 70-75% of the administered dose of radioactivity, was found to retain all three radiolabeled positions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898342 TI - Quantitative analysis of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine metabolism in isolated rat hepatocytes. AB - The biotransformation of the tertiary amine 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) was studied in isolated rat hepatocytes, in order to assess the relative contributions of the metabolic reactions previously described in studies with subcellular preparations. The oxidative pathway which produces the toxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) via the generation of the 2,3-dihydropyridinium derivative, MPDP+, accounted for approximately 90% of MPTP metabolism by hepatocytes. Mitochondrial monoamine oxidase type B (MAO B) was specifically responsible for the initial step of this conversion. In the endoplasmic reticulum, cytochrome P-450 catalyzed the demethylation of MPTP to form PTP, while the flavin-containing monooxygenase (FMO) was responsible for the generation of MPTP N-oxide. No other metabolite was detected in our hepatocyte incubations under any of the experimental conditions used. After pretreatment with the specific MAO B inhibitor, deprenyl, the rates of production of the two microsomal metabolites were enhanced, but the overall rate of MPTP conversion decreased by more than 60%. On the other hand, no significant difference in the rate of MPTP metabolism was found after the inhibition of cytochrome P-450 by SKF 525-A or with the use of methimazole, a competitive substrate for FMO. The SKF 525-A and methimazole treatments selectively inhibited the formation of PTP and MPTP N-oxide, respectively, but had no significant effect on the rate and extent of MPTP toxicity. MPP+ was the only metabolite which accumulated within the cell compartment under all the experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898343 TI - Cyclosporine-phenytoin interaction. AB - Cyclosporine (CsA), an immunosuppressant, is used widely to prevent rejection of transplanted organs. It is extensively metabolized in the liver by hydroxylation and demethylation. Since phenytoin is used extensively post-transplant as an anti convulsant, we studied the effect of chronic treatment with phenytoin on CsA by determining the disposition of CsA, prior to and after chronic treatment with phenytoin (30 mg/kg, po) for 5 days. CsA was analyzed by HPLC. The clearance (CL) of CsA was significantly enhanced following treatment with phenytoin when compared to the CL values obtained pretreatment (15.46 +/- 0.76 vs. 25.3 +/- 3.11 ml/min/kg). There were no significant changes in the volume of distribution of CsA. From the above data, we conclude that phenytoin probably induces the metabolism of CsA. PMID- 2898344 TI - N-benzylimidazole, a high magnitude inducer of rat hepatic cytochrome P-450 exhibiting both polycyclic aromatic hydrocarbon- and phenobarbital-type induction of phase I and phase II drug-metabolizing enzymes. AB - The effects of N-benzylimidazole on hepatic microsomal and cytosolic drug metabolizing enzymes were compared to the effects produced by phenobarbital, beta naphthoflavone, a polycyclic aromatic hydrocarbon, and Aroclor 1254, a polychlorinated biphenyl mixture. N-Benzylimidazole was a "high magnitude" inducer of male rat hepatic cytochrome P-450, inducing cytochrome P-450 over 3 times above control. N-Benzylimidazole exhibited mixed type induction of cytochrome P-450, producing both polycyclic aromatic hydrocarbon- and phenobarbital-type induction. There was no evidence of imidazole (isoniazid) type induction characteristics. Microsomes from rats treated with either Aroclor 1254 or N-benzylimidazole showed a common pattern of induction of the cytochrome P-450 dependent properties and glucuronosyltransferase activities, and the electrophoretic profiles of proteins were also similar. Cytosolic glutathione transferase activity was also induced similarly after treatment with the two agents. PMID- 2898346 TI - Pharmacokinetics and tissue distribution of recombinant human tumor necrosis factor-alpha in mice. AB - The serum pharmacokinetics and the major organs of accumulation of recombinant human tumor necrosis factor-alpha (rHuTNF) were determined in BDF1 mice after intravenous and intramuscular administration. Serum concentrations of immunoreactive protein were determined by enzyme-linked immunosorbent assay, and radioactivity was quantitated by beta and gamma scintigraphy. The serum pharmacokinetics of labeled and unlabeled rHuTNF were identical when administered by the intravenous route. After intravenous doses of 165 to 320 micrograms/kg, the clearance was 2.9-3.6 ml/hr, the initial volume of distribution was 1.4-1.6 ml (70-80 ml/kg), and the half-life was 18.5-19.2 min. Intramuscular administration of 320 micrograms/kg resulted in a peak serum concentration of 112 ng/ml. The time of the peak concentration was 1 hr, and the bioavailability of the intramuscular dose was 12%. The data suggest that the disposition of this protein may be biexponential. If this is the case, the terminal phase would appear to account for less than 1% of the total AUC. Since serum concentrations in the terminal phase are at the sensitivity limit of the assay, a single half life is reported. 125I-Labeled and metabolically labeled 3H-rHuTNF were used to examine tissue distribution. After intravenous 125I-rHuTNF administration, the rank order of accumulation of the 125I-radiolabel in the major organs (per cent dose per organ over 1440 min) was: liver greater than kidney greater than lung greater than heart greater than spleen. This rank order of accumulation was confirmed by intravenous 3H-rHuTNF administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898345 TI - Cytochrome P-450-dependent formation of ethylene from N-nitrosoethylamines. AB - Ethylene was identified as a metabolite of N-nitrosodiethylamine (NDEA) as well as of N-nitrosomethylethylamine and N-nitrosoethylbutylamine. The formation of ethylene from these carcinogenic compounds is cytochrome P-450- and NADPH dependent. With NDEA, the rate of the reaction in rabbit liver microsomes is increased by treatment of the animals with phenobarbital or ethanol, which are known to induce the synthesis of P-450 form 2 and P-450 form 3a (P-450ALC), respectively, and the activity is inhibited by anti-P-450 form 2 or form 3a IgG. The rate of ethylene formation is about 10-fold higher in nasal microsomes than in hepatic microsomes. In a reconstituted system, P-450 form 3a is the most active in ethylene formation from NDEA, followed by forms 2 and 4. It has been proposed by others that the alpha-hydroxylation of N-nitrosodialkylamines leads to the formation of an aldehyde and an alkyl diazonium ion, which, with the loss of N2, yields an alkyl carbonium ion capable of producing the corresponding alcohol or binding macromolecules through electrophilic reactions. In the case of the N-nitrosoalkylethylamines we have studied, the ethyl carbonium ion produced could, in addition, generate ethylene by proton elimination. PMID- 2898347 TI - Modulation of trans-4-acetylaminostilbene metabolism in the rat by methylcholanthrene and phenobarbital and its relevance for acute toxicity. AB - trans-4-Acetylaminostilbene (trans-AAS) is acutely toxic to rats. Animals can be protected from the effects of a lethal dose by pretreatment with methylcholanthrene (MC), but not with phenobarbital (PB). In order to study the effects of these pretreatments on pharmacokinetic parameters, single, acute toxic doses of 3H-trans-AAS were orally administered to female Wistar rats and metabolism and excretion studied in untreated and PB- and MC-pretreated animals. MC pretreatment enhanced the rate of metabolism and the excretion of metabolites into the bile, but did not alter urinary excretion. After 3 days, 46, 86, and 52% of the administered dose was excreted, respectively, in untreated, MC-pretreated, and PB-pretreated animals. MC pretreatment modified both phase I and phase II metabolism of trans-AAS. Urinary excretion of unconjugated metabolites was decreased accompanied by an increased formation of sulfates. Biliary excretion of glucuronides and conjugated polar metabolites was increased by MC pretreatment. It is concluded that MC protects rats from acute trans-AAS toxicity by increasing the rate of total metabolism and enhancing metabolic (conjugation) pathways of inactivation relative to putative activation by oxidative metabolism. PMID- 2898348 TI - Marked interspecies differences between humans and pigs in cyclosporine and prednisolone disposition. AB - Pigs have been used extensively in various transplantation protocols. Immunosuppressive therapy is usually performed by steroids and cyclosporine A (CyA). For rational dosage of these xenobiotics, their pharmacokinetics should be characterized. Therefore, we investigated the kinetics of prednisolone, an immunobiologically active steroid, after oral and iv administration, and of CyA, after oral and iv dosing, in seven pigs and compared these results with those obtained in 20 renal transplant patients. The mean area under the blood concentration versus time curve of CyA (HPLC measurements) was lower in pigs than in humans after oral (67 +/- 31 micrograms/ml x min vs. 296 +/- 101 micrograms/ml x min) and after iv (358 +/- 71 micrograms/ml x min vs. 858 +/- 292 micrograms/ml x min) doses of CyA. Compared to humans, pigs had lower concentrations of total prednisolone--assessed by HPLC--after oral prednisone (7.1 +/- 4.3 micrograms/ml x min vs. 297.9 +/- 75.6 micrograms/ml x min) and after iv prednisolone (26.8 +/- 9.5 micrograms/ml x min vs. 373.3 +/- 77.7 micrograms/ml x min). The plasma concentrations of both agents, lower in pigs than in humans, were attributable to an increased volume of distribution, an increased clearance, and more of a diminished systemic availability in pigs than in humans. Thus, to obtain the same target concentrations of CyA and prednisolone in both species, pigs require about 2 to 4 times higher iv or oral doses of CyA and 10 to 30 times higher iv or oral doses of steroids. PMID- 2898349 TI - Effect of serum from renal failure and cirrhotic patients on the blood-brain barrier permeability to DL-propranolol in rats. AB - Our previous studies using an in vivo tissue-sampling single-carotid injection method have shown that the transport of DL-propranolol into rat brain is inhibited by the serum from rats with uranyl nitrate-induced acute renal failure. The present studies were designed to examine the effect of serum from patients with renal or liver disease on the transport of DL-propranolol into the rat brain. While the binding of DL-propranolol to serum from cirrhotic patients was significantly decreased compared to normal serum, there was no change for the serum from patients with renal failure. In the carotid injection studies, the brain transport parameters such as the brain uptake index (BUI), the unidirectional extraction ratio (ET), the blood-brain barrier permeability surface area product (PSapp), and PSapp corrected for the unbound fraction (PSuapp) in rats injected with serum from patients with renal failure were significantly reduced to approximately 40-53% of those in controls. No change in BUI, ET, and PSapp was found in rats injected with serum from cirrhotic patients. However, the cirrhotic patients adopted in the present study had relatively mild liver disease (judging from the biochemical blood test), and we cannot refer to the more severe cirrhotic patients only from this study. Moreover, significant correlations were observed between the biochemical parameters (blood urea nitrogen, serum creatinine concentration) representing the degree of renal failure and the transport parameters (ET, PSapp, or PSuapp) of DL propranolol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898350 TI - Metabolism of cyclosporin A. III. Interaction of the macrolide antibiotic, erythromycin, using rabbit hepatocytes and microsomal fractions. AB - The interaction between cyclosporin A (CsA) and the macrolide antibiotic, erythromycin, has been studied in freshly isolated rabbit hepatocytes and in rabbit liver microsomal fractions. In hepatocytes, CsA was rapidly accumulated inside the cells and metabolized to its different groups of derivatives (mono- and/or dihydroxylated and/or N-demethylated metabolites) [Fabre, Bertault-Peres, Fabre, Maurel, Just, and Cano: Drug Metab. Dispos. 15, 384 (1987)]. In the presence of erythromycin in the extracellular compartment, CsA metabolism was inhibited in a concentration-dependent manner. However, erythromycin did not affect intracellular CsA accumulation and binding of CsA to its intracellular protein binding site(s). Since CsA was specifically metabolized by the cytochrome P-450 LM3c isozyme [Bertault-Peres, Bonfils, Fabre, Just, Cano, and Maurel: Drug Metab. Dispos. 15, 391 (1987)], we further studied the effect of erythromycin on CsA metabolism by liver microsomal fractions. In the presence of erythromycin, CsA metabolism was also decreased. Lineweaver-Burk analysis of erythromycin-CsA interaction demonstrated that erythromycin was a competitive inhibitor (Ki = 156 microM) of CsA metabolism (Km = 0.43 microM; Vmax = 4.8 nmol/min). In agreement with these data, CsA inhibited (i) erythromycin N-demethylation to a large extent and (ii) the appearance of the erythromycin-cytochrome P-450 LM3c complex. We could conclude that the interaction between CsA and erythromycin most likely results from the fact that both drugs are extensively metabolized by the same cytochrome P-450 form: P-450 LM3c or P-450 III A4 according to the new nomenclature.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898351 TI - The metabolism and disposition of fenofibrate in rat, guinea pig, and dog. AB - The metabolism and disposition of orally administered single doses of [14C]fenofibrate (isopropyl 2-[4-(4-chlorobenzoyl)phenoxy]-2- methylpropionate) have been studied in rat, guinea pig, and dog. In rats, the urinary excretion of 14C in 5 days varied from 11 to 51% of the dose and was markedly dependent upon the dose form given. The interpretation of these data in terms of factors affecting the absorption of fenofibrate from the gut is complicated by the enterohepatic recirculation of metabolites. The tissue distribution of 14C after oral administration of an ethanolic solution of fenofibrate has been studied in the rat. The only tissues in which the concentration of 14C exceeded that in the blood were the organs of absorption and elimination, the gut, liver, and kidneys. Guinea pigs excreted 53% of the dose in the urine in 5 days, with a further 34% in the feces, while in dogs the corresponding figures were 9% and 81%, respectively. In all three species, all the urinary metabolites were products of ester hydrolysis, and the principal excretion product was "reduced fenofibric acid" which arose by subsequent carbonyl reduction. Glucuronidation of fenofibric acid and "reduced fenofibric acid" was a very minor reaction in the rat and guinea pig and was not detected in the dog. In addition, polar unknown metabolite(s) were detected in all three species, but were not investigated further. The results are discussed in terms of the comparative disposition of fenofibrate and other hypolipidemic agents and the contribution of these findings to the safety assessment of such drugs. PMID- 2898352 TI - Pre- and postweaning development of drug-metabolizing enzyme activities in small intestine and liver of rats. AB - The postnatal development of NADPH-cytochrome c reductase, UDP glucuronosyltransferase, selenium-dependent glutathione peroxidase, glutathione-S transferase activities, total non-protein sulfhydryls, and cytochrome P-450 contents was compared in small intestine and liver of male Wistar rats from 18 to 60 days of life. In the intestine, main age-related changes affected conjugation enzymes which were increased rapidly by a factor of 4 during the weaning time and remained unchanged thereafter. Development in the rat was accompanied by changes in cytochrome P-450 content and NADPH-cytochrome c reductase activity only in the liver. In both organs, glutathione concentration and selenium-dependent glutathione peroxidase activity were not significantly modified between 18 and 60 days. In the liver, we observed discontinuities in the developmental pattern of UDP-glucuronosyltransferase, and the ontogenesis of glutathione-S-transferase activities differed according to the substrate metabolized. PMID- 2898353 TI - The rat biliary and urinary metabolism of the N6-methylated derivative of elliptinium acetate, and antitumor agent. AB - The rat biliary and urinary metabolism of N2,N6-dimethyl-9-hydroxyellipticinium (an N6-methyl derivative of elliptinium acetate, an antitumor agent) is reported. Two main metabolites have been identified: the glucuronide and sulfate derivatives by conjugation of the hydroxy group at position 9. Excretion profiles in bile and urine are also given. It has to be noted that no metabolite corresponding to a demethylation at the indolic nitrogen has been identified. However, the evidence for an increased concentration of the oxidized form of glutathione in bile during the drug excretion supports the hypothesis of an oxidative metabolism of this drug in rat liver. PMID- 2898354 TI - Effect of pH on acyl migration and hydrolysis of tolmetin glucuronide. PMID- 2898355 TI - Identification of two metabolites of a penem (Sch 34343) in human urine. PMID- 2898356 TI - Efflux of cimetidine from the rat cerebrospinal fluid. PMID- 2898357 TI - Inhibition of cimetidine transport by creatinine in luminal membrane vesicles prepared from rabbit kidney. PMID- 2898358 TI - Metabolism of 7-ethoxyresorufin by phenobarbital or Aroclor 1254 pretreated mice. PMID- 2898359 TI - Localization of pancreastatin immunoreactivity in porcine endocrine cells. AB - Pancreastatin is a peptide isolated from the porcine pancreas and shown to inhibit insulin release. We have studied the immunocytochemical distribution of pancreastatin in three porcine endocrine tissues: pancreas, gut, and adenohypophysis. Pancreastatin-specific immunoreactivity was found in all three locations and distributed to numerous cells. In the pancreas, we performed the alternate labeling of consecutive thick (immunofluorescence) or thin (protein A gold) sections and we observed that pancreastatin colocalizes to secretory granules of insulin and somatostatin-containing cells. The relationship of pancreastatin to chromogranin A is discussed. PMID- 2898360 TI - Calmodulin dependence of somatostatin release stimulated by growth hormone releasing factor. AB - Experiments were performed in vitro to examine the possible role of calcium and calmodulin in GRF-induced somatostatin (SRIF) release from the median eminence. Adult male rats were used as tissue donors. The median eminences were first prestimulated in 0.4 ml Krebs Ringer bicarbonate glucose buffer (pH 7.4) containing bacitracin at 37C in an atmosphere of 95% O2, 5% CO2 with constant shaking for 30 min. When calcium was omitted, this medium was used during the prestimulation and stimulation periods. After prestimulation, the medium was discarded and replaced by medium containing the different substances to be tested (GRF, EGTA, calcium channel blockers, and calmodulin inhibitors). The stimulation of SRIF release induced by 10(-10) M GRF was not inhibited by omission of extracellular calcium or when the remaining CA+2 was chelated with 10(-4) M EGTA. The calcium channel blockers, nifendipine and verapamil (10(-6) M), failed to alter the increase of SRIF release induced by rGRF. Three calmodulin inhibitors were employed to examine the possible influence of calmodulin on GRF-induced SRIF release. Trifluoperazine (10(-6) M), triflupromazine (10(-6) M) and penfluridol (10(-7) M) had an inhibitory effect on the stimulation of SRIF release induced by GRF and failed to alter resting release. Thus, GRF can evoke SRIF release independently of extraterminal Ca+2 concentration and Ca+2 influx into the nerve terminals, but the releasing process involves translocation of Ca+2 from intracellular stores. The inhibitory effect of the calmodulin inhibitors on GRF induced SRIF release, suggests that the translocated Ca+2 must bind to calmodulin in order to release SRIF. PMID- 2898361 TI - Decidual prolactin (PRL)-releasing factor stimulates the synthesis of PRL from human decidual cells. AB - Previous studies from our laboratory demonstrated that the acute release of PRL from human decidual tissue is stimulated by a 23.5 kilodalton placental protein which we designated decidual PRL-releasing factor (PRL-RF). To determine whether PRL-RF may also affect the synthesis of PRL and/or cause a secondary increase in PRL release, we have examined the effects of purified PRL-RF on the synthesis and release of PRL over a 96-h period. Exposure of dispersed decidual cells to PRL-RF (0.5 microgram/ml) stimulated a biphasic increase in PRL release with acute transient stimulation during the first 0.5 h and a delayed and sustained stimulation beginning about 8 h after exposure which persisted for the duration of the 96 h. The amounts of PRL released from PRL-RF-exposed cells after 0.5, 8, 12, 24, and 96 h were 321.2 +/- 36.2 (mean +/- SEM, n = 3), 110.2 +/- 5.3, 138.2 +/- 7.2, 194.5 +/- 11.2, and 201.5 +/- 14.2% that of control cells. Studies of the de novo synthesis of [35S]methionyl PRL indicated that the increase in PRL release after the first few hours of exposure to PRL-RF was secondary to an increase in PRL synthesis. Somatostatin (100 nM) inhibited the acute stimulatory effect of PRL-RF, but had no effect on the delayed stimulation of PRL release. On the other hand, cycloheximide (20 microM) completely inhibited the secondary increase in PRL release in response to PRL-RF but had no effect on the acute release. These results demonstrate that PRL-RF stimulates both the synthesis and release of decidual PRL. PMID- 2898363 TI - Secondary prevention reinfarction Israeli nifedipine trial (SPRINT). A randomized intervention trial of nifedipine in patients with acute myocardial infarction. The Israeli Sprint Study Group. AB - The efficacy of nifedipine in the prevention of post-infarction morbidity and mortality was evaluated in a double-blind clinical trial of 2276 survivors of acute myocardial infarction recruited from the cardiac departments of 14 Israeli hospitals. The patients were randomized to either nifedipine 30 mg day-1 or placebo between 7 and 21 days after their hospitalization for the acute event. Baseline characteristics of patients in each group were virtually identical for most pertinent variables. Mortality during an average 10-month follow-up period was 5.7% in the placebo group and 5.8% among those receiving nifedipine. Nonfatal recurrent myocardial infarction occurred in 4.8% and 4.4% of placebo and nifedipine patients, respectively. Administration of nifedipine according to the protocol used in the present study had no effect on cardiac events in survivors of acute myocardial infarction. PMID- 2898365 TI - Successful treatment of tardive and spontaneous dyskinesias with corticosteroids. AB - Three patients, 2 with tardive dyskinesia and 1 with senile chorea, were successfully treated with corticosteroids during an observation period of up to 5 months. Permanent complete relief or pronounced improvement of the dyskinesias was observed at a dosage of 5 mg prednisolone/day. Possible interactions between the putatively hyperactive dopaminergic system and corticosteroids are discussed. PMID- 2898362 TI - Inhibitory effect of platelet-activating factor (PAF) on luteinizing hormone releasing hormone and somatostatin release from rat median eminence in vitro correlated with the characterization of specific PAF receptor sites in rat hypothalamus. AB - Platelet-activating factor (PAF) exhibits a wide range of biological activities, including the stimulation of secretory processes in various cell types. However, little is known regarding its possible influence on the release of brain neuropeptides. In the present study we have examined the effect of PAF on the release of three hypothalamic releasing hormones in adult male rats, and have characterized the presence of specific PAF binding sites in rat hypothalamic membranes. PAF decreased LHRH and somatostatin (SRIF) release from the median eminence with a maximal inhibition at 10(-14) M for both neuropeptides, whereas GRF release was not significantly altered. Moreover, PAF strongly counteracted the Ca2+ ionophore A 23187-stimulated release of LHRH and SRIF from median eminence and medial basal hypothalamus (greater than 50% inhibition). These results suggest an involvement of Ca2+ dependent events in PAF action. This inhibitory effect was specifically exerted at a hypothalamic site because PAF failed to depress LH and GH release from the anterior pituitary. A specific, reversible and saturable binding of [3H]PAF to membrane preparations of rat hypothalamus was demonstrated and two classes of binding sites were characterized. The affinity (KD) of each binding class was 2.14 +/- 0.32 nM and 61.63 +/- 16.4 nM, respectively, and the corresponding maximal number of each binding class was 25.41 +/- 3.2 fmol/mg protein and 146.2 +/- 47.5 fmol/mg protein. In the same conditions no specific binding was observed using rat pituitary membranes. The specificity of PAF analogs for these binding sites was well correlated to their relative effectiveness in altering LHRH and SRIF release (order of potency: L-652,731, kadsurenone greater than BN 52021 greater than Lyso PAF). These data suggest that the binding sites identified in the hypothalamus have the characteristics expected of a specific PAF receptor and that PAF effect on neuropeptides release is a receptor-mediated process. PMID- 2898364 TI - Thyroid uptake of MIBG in Sipple's syndrome. AB - The use of the adrenomedullary tracer metaiodobenzylguanidine (MIBG) in the localization of medullary carcinoma of the thyroid (MCT) is based on the embryologic relationship of the APUD cell series. The authors report the results obtained in six patients with MCT: two had Sipple's syndrome and four sporadic forms of the disease. MIBG uptake by the CMT was observed in both cases of Sipple's syndrome and in only one of the other cases. Scintigraphic detection seems to depend on the clinical features, the size of the tumour and also on the part played by its secretory function. MCT would thus appear to be more frequently visualized by MIBG in cases of Sipple's syndrome than in sporadic cases. The procedure therefore seems useful in the diagnosis, follow up and even in the treatment of MCT. PMID- 2898366 TI - Prediction of neuroleptic on-drug response in schizophrenic in-patients by EEG. AB - The subjects were 34 acutely ill in-patients who met the RDC criteria of schizophrenic psychosis, and 4 EEGs were recorded from each patient before, 2 h and 24 h after oral intake of a single dose of 150 mg perazine, and on the 28th day of the neuroleptic treatment period. As a criterion of clinical response a decrease of at least 66% in the schizophrenia-specific sum score of the Brief Psychiatric Rating Scale on day 28 relative to the baseline value was decided upon. The EEGs were assessed using a newly developed procedure which takes into consideration 4 derivations simultaneously. As we tried to search out EEG variables with predictive value the statistical data analysis underlying our findings should largely by regarded as exploratory. Independent of day, responders (R) showed a tendency towards more low voltage desynchronized epochs (non-A stage) than non-responders (NR). Thus, R exhibited a higher degree of dynamic variability or a broader range of control of the spontaneous vigilance fluctuation (dynamic lability) than NR (dynamic rigidity). Furthermore, R and NR differed with respect to their time-dependent changes of non-A epoch frequencies before medication. While R showed a monotonous increase which is typical for normals, NR did not. Because of considerable inter-individual variability these group differences could not be used for individual prediction of the therapy response. By means of a qualitative data analysis R could be distinguished from NR with regard to various test dose-induced changes of the topographical distribution of absolute alpha power. All the group differentiating variables showed a time course of the same kind: R showed a prompt and ample deflection and the same recovery of baseline; NR, in contrast, showed no significant deflections at all. These findings are in line with the results concerning the dynamics of vigilance and certain claims of earlier authors according to which EEG changeability should be decisive for therapeutic outcome.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2898367 TI - Identification of a multidrug resistance associated antigen (P-glycoprotein) in normal human tissues. AB - The multidrug resistance (NDR) phenotype describes a pattern of cross-resistance to unrelated compounds observed in mammalian cell lines selected in vitro for resistance to a single agent. Overexpression of a 170,000 dalton cell membrane glycoprotein (P-glycoprotein) is associated consistently with this phenotype in these cell lines. Recently, several human tumours have been shown to contain P glycoprotein and expression was greatest in tumours exhibiting clinical drug resistance. To explore further the significance of P-glycoprotein, we examined normal human tissues obtained at autopsy by polyacrylamide gel electrophoresis and immunoblotting using a monoclonal antibody directed against P-glycoprotein. We showed expression of P-glycoprotein in normal liver and small bowel mucosa but not in other organs examined. This suggests there may be significant expression of P-glycoprotein in certain normal human tissues and any plan to exploit P glycoprotein clinically must take these findings into account. PMID- 2898368 TI - Decrease of plasma potassium due to inhalation of beta-2-agonists: absence of an additional effect of intravenous theophylline. AB - The effect on the plasma potassium concentration of inhalation of the beta-2 agonists fenoterol, salbutamol (albuterol), and terbutaline from metered-dose inhalers was studied in normal volunteers. All three drugs caused a significant, dose-dependent decrease, more pronounced for fenoterol and salbutamol than for terbutaline. Relative to the bronchodilating potency (one puff of fenoterol 0.2 mg is considered to be equivalent to two puffs of salbutamol 2 x 0.1 mg, or two puffs of terbutaline 2 x 0.25 mg), fenoterol had a more pronounced effect on plasma potassium than salbutamol or terbutaline. The systemic effect on plasma potassium seems to be related to the structure of the drugs: the more lipophilic the drug (fenoterol) the sooner the systemic symptoms appear and the more pronounced they are. The effects of theophylline alone, and combined with fenoterol, were also studied. The intravenous infusion of theophylline (after placebo inhalation; maximal mean plasma concentration 14.9 +/- 2.2 mg l-1) caused a small but significant decrease of plasma potassium. There was no additive or synergistic effect when theophylline was added to fenoterol. It is concluded that inhalation of beta-agonists induces a decrease of plasma potassium, that this effect is relatively more pronounced for fenoterol than either salbutamol or terbutaline, and that it is not enhanced by the concomitant use of theophylline. Theophylline by itself causes a slight decrease in plasma potassium concentration. PMID- 2898370 TI - CD2 is involved in regulating cyclic AMP levels in T cells. AB - The human T lymphocyte-specific CD2 (T11) molecule, that regulates T cell activation, is capable of mediating increases of intracellular cAMP. Monoclonal antibodies directed to different epitopes of the CD2 molecule which either induce or inhibit T cell proliferation are capable of triggering an increase of cAMP comparable to that induced by reagents which activate adenylate cyclase. These results indicate that there is a relationship between the CD2 membrane molecule and the adenylate cyclase system. PMID- 2898369 TI - Effect of prednisolone and ketotifen on beta 2-adrenoceptors in asthmatic patients receiving beta 2-bronchodilators. AB - In 13 patients with bronchial asthma, who were on beta 2-adrenergic bronchodilator therapy, the effects of prednisolone and ketotifen on lymphocyte beta 2-adrenoceptor density and -responsiveness were investigated. The mean lymphocyte beta 2-adrenoceptor density and -responsiveness was significantly lower than in healthy controls, presumably due to the long-term beta 2-adrenergic bronchodilator treatment. Both prednisolone 100 mg i.v. and ketotifen 1 mg b.d.p.o. for 6 days rapidly improved lymphocyte beta 2-adrenoceptor function. 16 h after prednisolone and about 6 days after the first dose of ketotifen lymphocyte beta 2-adrenoceptor density and -responsiveness had risen to values within the range in normal volunteers. The improvement of lymphocyte beta 2 adrenoceptor function was accompanied by a significant increase in peak expiratory flow rate before and after inhalation of salbutamol. It is concluded that prednisolone and ketotifen may act beneficially on the recovery of beta 2 adrenoceptor responsiveness to beta 2-adrenergic bronchodilators in tolerant asthmatic patients. PMID- 2898371 TI - 'GABA shift' in vivo: enhancement of benzodiazepine binding in vivo by modulation of endogenous GABA. AB - The enhancement of benzodiazepine binding by gamma-aminobutyric acid (GABA) and its analogues has been described in detail in brain membrane preparations, but results in in vivo preparations such as tissue slices or animals treated with GABA modulators are conflicting. This 'GABA shift' in vitro has been reported for compounds with agonist effects at the benzodiazepine receptor but not for antagonists. We examined the effects of modulators of endogenous GABA on benzodiazepine receptor binding in vivo as determined by specific uptake of the benzodiazepine antagonist [3H]Ro 15-1788. Enhancement of radioligand uptake was observed in cortex, hypothalamus, hippocampus and pons-medulla 4 h after treatment with aminooxyacetic acid (AOAA), in cortex, cerebellum, hypothalamus, hippocampus and pons-medulla 0.5 h after treatment with valproic acid, and in cortex, cerebellum, hypothalamus and hippocampus 6 h after treatment with gamma vinyl-GABA. GABA concentrations were increased at each of these points, as were synaptosomal GABA concentrations in prior studies. In contrast, no changes in radioligand uptake or GABA concentrations were observed 12 and 24 h after gamma vinyl-GABA treatment. Increases in binding appeared to be due to increased apparent affinity at the receptor rather than a change in receptor number. These data indicate that binding of a benzodiazepine antagonist undergoes a GABA shift in vivo analogous to that observed with agonists in vitro. PMID- 2898372 TI - Effect of azelastine on the intracellular Ca2+ mobilization in guinea pig peritoneal macrophages. AB - Azelastine, an orally effective anti-allergic agent, has been demonstrated to inhibit the release of histamine and leukotrienes. This suggests that azelastine might alter the mobilization of intracellular Ca2+. We have examined the effect of azelastine on the change in intracellular free calcium concentration ([Ca2+])i) in guinea pig peritoneal macrophages induced by platelet activating factor (PAF-acether) or N-formylmethionyl-leucyl-phenylalanine (FMLP) using a fluorescent Ca2+ indicator, fura2. PAF-acether raised [Ca2+]i from 89 +/- 4 to 243 +/- 26 nM (n = 15) within 20 s after addition of PAF-acether in the presence of 2 mM EGTA. This indicates that the stimulation of macrophages by PAF-acether induced intracellular mobilization of Ca2+, and pretreatment with azelastine reduced the PAF-acether-induced increase in [Ca2+]i in a dose-dependent manner (IC50 = 16 microM). Azelastine also inhibited the FMLP-induced increase in [Ca2+]i. Furthermore, PAF-acether and FMLP both caused the release of prostaglandin E2 from macrophages, and pretreatment with azelastine reduced the PGE2 release dose dependently (IC50 = 10 microM). These results suggest that azelastine inhibits the release of Ca2+ from intracellular storage sites induced by PAF-acether or FMLP, and that this effect possibly causes reduction in the release of PGE2 from the cells. PMID- 2898373 TI - Interaction of calmodulin antagonists with alpha-adrenergic responses in pithed rats and in the perfused hindquarters of the rat. AB - The effect of calmodulin antagonists was studied on the alpha 1- and alpha 2 adrenoceptor-mediated increase in diastolic blood pressure in pithed rats and on the alpha 1-adrenoceptor-mediated reduction of flow in the perfused hindquarters of the rat. B-HT 920 was used as a selective alpha 2-adrenoceptor agonist in the pithed rat experiments, whereas cirazoline was used as a selective agonist for alpha 1-adrenoceptors. The latter was used after pretreatment with nifedipine (1 mg/kg) or phenoxybenzamine (30 micrograms/kg), revealing calcium influx insensitive and -sensitive mechanisms of vasoconstriction, respectively. Papaverine, calmidazolium and W-7 did not influence the dose-response curves for the agonists in the pithed rat experiments. The modest effects of high doses of flunarizine and bepridil on the dose-response curve for B-HT 920 and of trifluoperazine on the dose-response curve for cirazoline can be explained by the well-known calcium entry (flunarizine) and alpha 1-adrenoceptor-blocking (bepridil) effects of these drugs. Bepridil and calmidazolium caused an elevation of the cirazoline dose-response curves in the perfused rat hindquarters; flunarizine and trifluoperazine showed a parallel and dose-dependent displacement of the cirazoline dose-response curve to the right, whereas W-7 was inactive. Our results do not implicate calmodulin-associated effects in the alpha-adrenoceptor mediated vasoconstriction in pithed rats and in the perfused rat hindquarters. PMID- 2898374 TI - Adrenergic effect on the atrial natriuretic peptide secretion and vasoconstriction induced in the perfused rat heart by phorbol ester. AB - Infusion of a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), known to stimulate protein kinase C, caused a gradual, sustained increase in perfusate immunoreactive atrial natriuretic peptide (IR-ANP) concentration and a more rapid increase in perfusion pressure in the isolated perfused rat heart. Administration of isoprenaline resulted in a rapid rise in IR-ANP release whereas methoxamine induced a sustained increase in IR-ANP secretion into the perfusion fluid. Methoxamine, when infused in combination with TPA, enhanced both IR-ANP secretion and the increase in perfusion pressure produced by phorbol ester. Isoprenaline also acted synergistically on TPA-induced IR-ANP release but attenuated the coronary vasoconstriction produced by phorbol ester. The TPA-induced increase in IR-ANP secretion was attenuated significantly by infusion of atenolol and slightly by infusion of prazosin, neither of which affected TPA-induced vasoconstriction. The vasoconstrictor response to infusion of phorbol ester was similar but the secretory response was attenuated in hearts from rats pretreated with reserpine. The results indicate that adrenoceptor stimulation interacts differentially with phorbol ester-induced ANP secretion and vasoconstriction in the perfused rat heart. Our results also suggest that the effect of TPA on perfusion pressure appears to be due to its direct action on vascular smooth muscle cells but that a part of the TPA effect on ANP secretion may be an indirect one. PMID- 2898375 TI - Selectivity of ligand binding to opioid receptors in brain membranes from the rat, monkey and guinea pig. AB - Conditions for the equilibrium binding to opioid receptor of [3H]sufentanil (mu selective), [3H][D-Pen2,D-Pen5]enkephalin (delta selective), and [3H]U69,593 (kappa selective) were established in membranes from rat brain cerebrum, monkey cortex, or guinea pig cerebellum. The selectivity index of various opioid alkaloids and peptides in binding to the mu, delta, or kappa opioid receptors was expressed as the ratio of their EC50 values in displacing two selective radiolabeled ligands: [3H]sufentanil/[3H](D-Pen2,D-Pen5)enkephalin (selectivity: mu/delta), [3H]sufentanil/[3H]U69,593 (selectivity: mu/kappa), or [3H][D-Pen2,D Pen5]enkephalin/[3H]U69,593 (selectivity: delta/kappa). High resolution in binding selectivity was observed: in rat brain the mu/delta selectivity for Tyr-D Ala-Gly-(Me)Phe-Gly-ol and sufentanil were 0.02 and 0.03, whereas for [D-Pen2,D Pen5]enkephalin and ICI 174,864 they were 1,200 and 998. Compared to mu opiates, the specific binding of delta and kappa agonists was less sensitive to sodium. The results describe a routinely applicable methodological approach for the assessment of selective ligand binding to the mu, delta and kappa opioid receptors in rodent and monkey brain membranes. PMID- 2898376 TI - Correlation of inhibitory potencies of putative antagonists for sigma receptors in brain and spleen. AB - The putative sigma receptor antagonists, haloperidol, HR 375, BMY 14802 and BW 234U potently inhibited both [3H]d-N-allylnormetazocine binding to sigma receptors in brain homogenates and [3H]haloperidol binding to sigma receptors in spleen homogenates. An excellent correlation of inhibitory potencies in the two assay systems was obtained. The results support the view that [3H]d-N allylnormetazocine and [3H]haloperidol both label the same receptor populations, and suggest that sigma antagonists may be useful in elucidating physiological role(s) of sigma receptors in the nervous and immune systems. PMID- 2898377 TI - A new and specific non-NMDA receptor antagonist, FG 9065, blocks L-AP4-evoked depolarization in rat cerebral cortex. AB - L(+)-AP4 (2-amino-4-phosphonobutyrate) depolarized slices of rat cerebral cortex, when applied following a 2 min priming application of quisqualate. This response diminishes with time and is not seen after NMDA application. A new selective non N-methyl-D-aspartate (NMDA) antagonist, 6-cyano-7-nitro-2,3-dihydroxyquinoxaline (FG 9065), inhibits the L(+)-AP4 depolarization. It is argued that the response is mediated indirectly by postsynaptic quisqualate receptors. PMID- 2898378 TI - Rods are selectively altered by lead: I. Electrophysiology and biochemistry. AB - In vitro studies have demonstrated that lead selectively and reversibly depresses the rod photoreceptor component of the electroretinogram (ERG). To determine if low-level lead exposure during early postnatal development produced long-term selective rod deficits, we examined rod and cone ERG functions and cyclic GMP and cyclic AMP metabolism in adult control and lead-exposed rats. A-wave and b-wave voltage-log intensity and latency-log intensity functions, generated from single flash ERGs in fully dark-adapted rats, revealed that low-level lead exposure during early postnatal development caused a 23- and 18% decrease in maximum amplitude, a 1.0- and 0.5 log unit decrease in absolute sensitivity and a mean latency increase of 47- and 29%, respectively. Additional ERG experiments, using scotopically balanced stimuli and scotopic and photopic flicker fusion frequency functions, also demonstrated selective rod deficits. Cone ERGs, elicited by 30-Hz white flashes in the presence of a white background adapting light, were similar in control and lead-exposed rats. Lead exposure during early postnatal development caused cGMP levels in dark-adapted and light-adapted retinas to increase 40- and 25%, respectively, above controls whereas cyclic AMP levels remained unchanged. Light-activated cyclic GMP phosphodiesterase (cGMP-PDE) was inhibited 40% while guanylate cyclase activity was unchanged. The retinal lead concentration was 10(-6) M at the end of exposure (day 21) while at the time of ERG testing and biochemical analysis it was 10(-7) M. In vitro studies with adult control retinas incubated with 10(-9)-10(-4) M lead revealed a dose-response inhibition (10-40%) of cGMP-PDE between 10(-6)- and 10(-4) M lead and stimulation of guanylate cyclase (20-158%) only above 10(-4) M lead, indicating that cGMP-PDE is more sensitive to the direct effects of lead than the synthetic cGMP enzyme. These in vitro cyclic nucleotide metabolism results are similar to those we observed in vivo and both are consistent with the observed ERG changes. The selective rod-mediated amplitude, sensitivity and temporal deficits and the lack of effect on the cone ERGs clearly demonstrate that low-level lead exposure during early postnatal development causes a long-term selective disruption of rat rod photoreceptors. The relevance and applicability of these data to subclinical pediatric lead poisoning has yet to be established. PMID- 2898379 TI - Involvement of excitatory neurotransmitters in the damage produced in chick embryo retinas by anoxia and extracellular high potassium. AB - Chick embryo retinas were exposed for 40 min to anoxic conditions and the resulting histological changes were studied by light microscopy. A strong edematous response with severe swelling of the inner nuclear, inner plexiform and ganglion cell layers and numerous cells with pyknotic nuclei but very few dead cells were observed. These changes were qualitatively similar to those observed on retinas exposed to high potassium concentration or to glutamic acid. The deleterious effects of anoxia and high potassium concentration were not affected by the removal of calcium ions from the retina incubation medium but were prevented by gamma-D-glutamylglycine, an antagonist of excitatory amino acid receptors. These results suggest that the damage observed in retinas maintained under anoxia for 40 min is likely to be due to the release, from non-synaptic pools, of excitatory neurotransmitters, possibly glutamic and/or aspartic acids, evoked by the dissipation of the membrane ionic gradients. These events would be the first in a chain of toxic damage leading ultimately to cell death. PMID- 2898381 TI - Biochemical changes in progressive muscular dystrophy. XV. Distribution of radioactive glutamate and proximate composition of various components of skeletal muscle and liver in vitamin E-deficient dystrophic rabbits and 129/ReJ (dy/dy) mice. AB - The proximate composition of skeletal muscle and liver and the incorporation of radioactive glutamate into their various components were investigated in vitamin E-deficient rabbits and genetically dystrophic (dy/dy) mice during various stages of the disease. Total fat content in skeletal muscle was decreased in the early phase and increased in the terminal stage of both types of dystrophy. This component altered only in the liver of dystrophic mice, showing a reduction in the mild stage but returning later to normal values. Carbohydrate content was diminished in the skeletal muscle of both species at each stage of the disease. In the liver, however, it was elevated considerably in vitamin E-deficient rabbits, but was depressed in dystrophic mice. Protein content was decreased in the skeletal muscle of both dystrophic models. Similar results were obtained for amino acids, except that they were increased in the terminal stages of nutritional dystrophy. Analogous values were recorded for hepatic amino acids in nutritionally-induced and hereditary dystrophy (in rabbits and mice respectively). Incorporation of C14-glutamate into various components of skeletal muscle and liver in both models revealed divergent responses, depending upon the nature of the dystrophy, and the component in which incorporation was measured. These data indicate a rapid turnover of C14-glutamate in the skeletal muscle and liver of vitamin E-deficient and genetically dystrophic animals. Also, it is clear that the changes in the various components of skeletal muscle and liver, as well as the pattern of C14-glutamate incorporation, are different in the two types of dystrophy. PMID- 2898380 TI - Mesencephalic dopamine cell deficit involves areas A8, A9 and A10 in weaver mutant mice. AB - The mesencephalic dopamine (DA) cell system was examined in mice homozygous and heterozygous for the weaver (wv) gene and in wild-type controls to estimate the extent of cell losses associated with the genetically determined central DA deficiency observed in weaver homozygotes. Animals of the three genotypes (+/+, wv/+, wv/wv) were studied at postnatal day (P)20 and P90. Serial coronal sections were obtained through the brainstem. Half of the sections were immunolabeled with antiserum to tyrosine hydroxylase (TH). Cell counts were obtained in areas A8 (retrorubral nucleus, RRN), A9 (substantia nigra, SN), and A10 (ventral tegmental area, VTA). The counts were analyzed with repeated measures analysis of variance followed by individual comparisons among group means. In A8, weaver homozygotes did not differ significantly from wild-type controls at P20, whereas there was a significant difference of 56% at P90. In A9, weaver homozygotes differed significantly from wild-type mice by 42% at P20 and by 69% at P90. The decrease in cell number between P20 and P90 in weaver homozygotes was 54%. In A10, weaver homozygotes did not differ significantly from wild-type controls at P20, whereas there was a significant difference of 26% at P90. Cell numbers in all three areas of heterozygotes did not differ significantly from wild-type control values at either age point. These findings demonstrate that by three months of age homozygous weaver mutants exhibit nerve cell losses in all three areas of the mesencephalic DA cell system. Such losses account for the DA deficiency seen in striatal, limbic and cortical projection fields. PMID- 2898382 TI - Synthesis and beta-adrenergic blocking activity of oxipropanolamines of 3,4 dihydro-3-oxo-2H(1,4)benzothiazine. AB - The synthesis of a series of oxypropanolamines of 3,4-dihydro-3-oxo 2H(1,4)benzothiazine is reported. Some of these compounds proved more potent than propranolol and carteolol as beta-adrenergic blocking agents in in vitro tests. The 8-(3-tert-butylamino-2-hydroxy)propoxy-3,4-dihydro-3-oxo-2H(1,4) benzothiazine fumarate (XVI a), which gave better results, confirmed its remarkable activity in in vivo tests. PMID- 2898383 TI - The amino acid substitution in albumin Roma: 321 Glu----Lys. AB - Albumin Roma is an electrophoretically slow moving genetic variant of human serum albumin found in 22 unrelated families. The protein was isolated from the serum of a healthy, heterozygous subject. Analysis of CNBr fragments by isoelectric focusing allowed us to localize the mutation to fragment CNBr IV (residues 299 329). This fragment was isolated on a preparative scale by RP-HPLC and subjected to tryptic digestion. Sequential analysis of two abnormal tryptic peptides, purified by RP-HPLC, revealed that the variant arises from the substitution of glutamic acid 321 by lysine. This amino acid replacement, probably resulting from a point mutation in the structural gene, causes a change in the net charge of +2 units which is in keeping with the decreased electrophoretic mobility of the native protein. PMID- 2898384 TI - Kinetic limitations in the overall reaction of mitochondrial oxidative phosphorylation accounting for flux-dependent changes in the apparent delta GexP/delta mu H+ ratio. AB - Changes in J0, delta muH+ and delta GexP were investigated as a function of load. The flux control coefficients, particularly those of the adenine nucleotide translocator and H+-ATPase at the maximum rate of oxidative phosphorylation were seen to strongly depend on the phosphate concentration accounting in common for the highest share in flux control. There was no unique relationship observed between JP and delta muH+ in load-controlled, well coupled systems, but JP was found to depend on delta muH+ at excessive load and increasing proton leakage. All the results presented can be elucidated on the grounds of delocalized chemiosmotic coupling. PMID- 2898386 TI - The low activity of acetyl-CoA carboxylase in basal and glucagon-stimulated hepatocytes is due to phosphorylation by the AMP-activated protein kinase and not cyclic AMP-dependent protein kinase. AB - Acetyl-CoA carboxylase purified from isolated hepatocytes is activated dramatically by protein phosphatase treatment, concomitant with a reduction of the phosphate content from 3.7 to 1.1 mol/subunit. Glucagon treatment of the cells produces a further inactivation of the enzyme that is totally reversed by phosphatase treatment, and is associated with an increase in phosphate content of 0.8 mol/subunit, distributed in two peptides which contain the sites phosphorylated in vitro by the cyclic AMP-dependent and AMP-activated protein kinases. Sequencing of these peptides shows that the low activity of acetyl-CoA carboxylase is due to phosphorylation by the AMP-activated protein kinase, and not cyclic AMP-dependent protein kinase, even after glucagon treatment. PMID- 2898385 TI - A third human CALC (pseudo)gene on chromosome 11. AB - A genomic locus in man (CALC-III) containing nucleotide sequences highly homologous to both exon 2 and exon 3 of the CALC-I and -II genes, is described in this paper. The CALC-I gene produces calcitonin (CT) (encoded by exon 4) or calcitonin gene-related peptide (CGRP) (encoded by exon 5) in a tissue-specific fashion. The CALC-II gene produces a second human CGRP, but probably not a second CT. The CALC-III gene does not seem to encode a CT- or CGRP-related polypeptide hormone and is probably a pseudogene. Like the other two CALC genes, the CALC-III gene is located on human chromosome 11. PMID- 2898387 TI - Identification of alpha-subunit Lys201 and beta-subunit Lys155 at the ATP-binding sites in Escherichia coli F1-ATPase. AB - Binding of about 1 mol of adenosine triphosphopyridoxal to Escherichia coli F1 ATPase resulted in the nearly complete inactivation of the enzyme [(1987) J. Biol. Chem. 262, 7686-7692]. About two thirds of the label was bound to the alpha subunit, and the rest to the beta-subunit. The present study revealed that Lys201 in the alpha-subunit and Lys155 in the glycine-rich region of the beta-subunit are the major sites labeled with this reagent. Thus, these two residues might be located close to the gamma-phosphate of the bound ATP. PMID- 2898388 TI - Survey of mosquito fauna of northeastern region of India. PMID- 2898389 TI - Mosquito survey in Tirap and Subansiri districts of Arunachal Pradesh. PMID- 2898390 TI - Cutaneous T cell lymphomas and retrovirus infection. PMID- 2898391 TI - Maternal deaths in the less developed world: preventable tragedies. AB - A half million women die yearly around the world as a result of pregnancy. Many of these deaths are inaccurately classified and many others are not reported at all, but new demographic techniques have clarified causes of maternal mortality and improved estimates of rates. New data from several less developed countries suggest that many maternal deaths could be prevented by measures already demonstrated to be effective elsewhere. These include better antenatal and intrapartum care, contraception for women who want no more pregnancies, legal abortion to terminate unwanted pregnancies, and uterine aspiration and antibiotics for treatment of septic abortion. PMID- 2898393 TI - Vaginal birth after cesarean section: management debate. AB - Obstetric performance of 1847 women with previous cesarean section (CS) during the years 1983 and 1984 were studied. Vaginal birth after cesarean section (VBAC) was attempted in 94% of females with one previous CS, 4% in those with two previous CS, and one among the 70 patients with three or more previous CS. VBAC was achieved in 51% of those with one previous CS. It was successful in 60% of parturients with CS for non-recurrent causes, 36% of CS for cephalopelvic disproportion (CPD) and in 64% of those with a prior vaginal delivery. Uterine scar dehiscence was found in 0.9% of all patients with a previous CS. A failed attempt with Ventouse to achieve VBAC caused maximum maternal and perinatal morbidity. PMID- 2898392 TI - Preliminary report of an identification mission for safe motherhood, Senegal: putting the M back in M.C.H. AB - The Government of Senegal, in keeping with the priority given to women and children in its health programs, requested the assistance of the United Nations Development Program (UNDP) in identifying and executing a program to diminish maternal mortality in that country. A UNDP "Mission of Identification" was carried out in response to this initiative. The preliminary results of this mission confirm that the issue of maternal safety is of primary concern not only to the government but also to women in the Republic of Senegal. The methodology employed during this mission allowed the team of national and international experts to confirm the level of this concern and to identify four major potential areas of intervention. Quantitative goals for the program have been set and estimates for the efficacy of each of the intervention areas indicate that intervention through the timely provision of access to emergency surgical services and appropriate prenatal care will yield the largest reduction. The feasibility of providing interventions in each of the four areas was also addressed during the mission. This methodology will be applicable to other settings as Third World countries begin to address the problem of excessive maternal mortality. PMID- 2898394 TI - Obstetric complications of macrosomic babies in African women. AB - A prospective analysis has been made on 145 consecutive deliveries resulting in babies weighing 4.5 kg and above delivered at the University of Nigeria Teaching Hospital (U.N.T.H.), Enugu, over a 1-year period (1985). Babies weighing 4.5 kg and over are regarded as macrosomic babies. The incidence of macrosomic babies in this study is 11 per thousand deliveries or 1 in 90. Factors that predisposed to the birth of macrosomic babies include: excessive weight gain during the course of pregnancy, tall height of the woman, multiparity and prolonged gestation. Diabetes mellitus was not a significant factor. Complications include prolonged labor, post-partum hemorrhage, ruptured uterus, shoulder dystocia and an increased perinatal mortality rate. Maternal mortality was also increased. Ninety percent of the multiparous women achieved spontaneous vaginal delivery while only 42% of the primigravidae achieved vaginal delivery. The implications are discussed. PMID- 2898395 TI - Electronic fetal heart rate monitoring during cesarean section. AB - Fetal heart rate (FHR) response to cesarean section was studied in 65 patients. Induction of anesthesia, skin, fascial, peritoneal and bladder flap incisions were not associated with a change in FHR. Abdominal preparation was associated with FHR decelerations in 15% of cases. Myometrial incision was followed by FHR deceleration in 11% of cases. No correlation between the incision/delivery (I-D) interval and FHR changes was seen. PMID- 2898396 TI - Induction of dead fetus labor with 15-(S)-methyl prostaglandin F2 alpha. AB - This study examines whether labor can be induced with the intramuscular administration of 15-(S)-methyl prostaglandin F2 alpha in cases of intrauterine fetal death. The success rate of labor induction in the studied group was 93.75%, and was the same for primigravid and multigravid patients. The authors conclude that the prophylactic administration of an analgesic potentiator, an anti-emetic and an anti-diarrheal is advantageous to a woman's tolerance of the prostaglandin. PGF2 alpha is a quick and effective drug for use in the induction of labor to terminate pregnancies with intrauterine fetal death and offers tolerable side-effects when used with adjuvant medication. PMID- 2898397 TI - Intrapartum levels of trace metals in maternal blood in relation to umbilical cord blood values: lead, iron, copper, zinc. AB - The study was designed to measure the gradients of lead, iron, copper and zinc from maternal blood to cord blood in pregnant urban and rural women. The concentrations of iron, copper, zinc and lead were measured by means of atomic absorption spectometry (AAS) in whole blood of 100 normal parturients and 92 of their neonates. Levels of lead in cord blood were not significantly different from those in maternal blood. This ratio was associated with similar iron and zinc ratios. Neonatal birth weight was negatively correlated with maternal copper levels, whereas cord blood zinc values positively correlated with placental weight. Rural women showed higher maternal to cord blood lead ratios than urban women. The implications of these findings are discussed. PMID- 2898398 TI - Fetal biparietal diameter and head circumference measurements: results of a longitudinal study in Zimbabwe. AB - In a longitudinal study in Harare, Zimbabwe, 1233 biparietal diameter and 857 head circumference measurements were obtained from the fetuses of 190 women. Weekly mean values and the two standard deviations were calculated for both the biparietal diameter and head circumference from 12 to 40 weeks of pregnancy. There was little difference between these values and some Caucasian and African standards. Comparison was also made of the weekly biparietal diameter growth rate between our results and those from one study in West Africa. The possible reasons for the differences are explained. PMID- 2898399 TI - The hemoglobinopathies and pregnancy in Lagos. AB - Thirty-four patients with abnormal hemoglobin were studied through 42 pregnancies under one obstetrician. There were 30 patients with sickle cell anemia (HbSS), two with sickle cell hemoglobin C disease (HbSC) and two with homozygous hemoglobin C disease (HbCC). There were 39 live births (including one pair of twins), and four perinatal deaths. The patients with HbSC and HbCC had five uncomplicated pregnancies and deliveries. Of the 36 pregnancies in patients with HbSS one aborted at 12 weeks. Intra-uterine growth retardation (14.3%) and pregnancy-induced hypertension (14.3%) were the most serious pregnancy complications. No patient had more than one crisis. Only one out of the 10 patients transfused needed more than two units of blood throughout pregnancy. The mean gestation at delivery was 37.5 +/- 3.2 (S.D.) weeks. The mean birth weight was 2.7 +/- 0.6 (S.D.) kg. The perinatal mortality was 114.3 per thousand live births and there was one maternal death. PMID- 2898400 TI - Evaluation of tolerance of and response to iron dextran (Imferon) administered by total dose infusion to pregnant women with iron deficiency anemia. AB - Six hundred twenty-three pregnant women with iron deficiency anemia received iron dextran Imferon by total dose infusion (TDI). Two dose levels were compared in respect of tolerance and hemoglobin response. The incidence of delayed reactions was significantly higher in the high dose group (P less than 0.01) but there was no significant difference in the incidence of reactions occurring during the infusion. These findings are discussed in relation to the hemoglobin response. PMID- 2898401 TI - Cervical incompetence: a 24-year review. AB - Three hundred nineteen cervical cerclages performed in 264 pregnant women were retrospectively studied. The diagnosis of cervical incompetence was established by the obstetrical history, hysterosalpingography, ultrasound screening and vaginal examination. All cervical cerclages were applied between 14 and 17 weeks gestation according to Shirodkar's technique except 49 emergency cases between 18 and 26 weeks gestation for which other techniques were chosen. The incidence of preterm deliveries (26-37 weeks gestation) decreased from 39.7% to 14.23% (P less than 0.001) and that of full term pregnancies increased from 20.04% to 75.74% (P less than 0.001). The number of neonates weighing less than or equal to 2000 g decreased from 44.20% to 11.38% (P less than 0.001) and those weighing greater than or equal to 2500 g increased from 44.83% to 75.82% (P less than 0.001). Perinatal mortality after cerclage declined from 28.21% to 5.52% (P less than 0.001). There was no increase in congenital defects. An increased rate of breech presentation (5.32%) and cesarean section (20.38%) was noticed. The repeated cerclage in consequent pregnancies did not seem to influence the duration of gestation. In emergency cases the rate of preterm deliveries was 53.06%, of full term pregnancies 12.25%, of newborns with birthweight less than or equal to 2500 g 31.77% and of those with birthweight greater than 2500 g 19.23%. Perinatal mortality in emergency cases was 42.3%. An increase in aerobic and anaerobic pathological flora was noticed in postoperative cervical cultures. PMID- 2898402 TI - Prevalence of urinary incontinence in middle-aged women. AB - An anonymous questionnaire was used to interview 946 premenopausal women (age 29 52 years), previously either hysterectomized or laparoscopically sterilized, concerning disorders of the urinary tract. Of the 750 (79.3%) women that responded, 307 (40.9%) admitted to some degree of urinary disorder. The prevalence of urinary disorders was 170/415 (40.9%) for the women with a previous supravaginal or total hysterectomy and 137/335 (40.8%) for the women in the sterilization group. Of the responding women 85 (11.3%) experienced a urinary loss sufficient to necessitate the wearing of a sanitary napkin or change of underclothing several times a day. PMID- 2898403 TI - A cost-effective but safe protocol for the staging of invasive cervical carcinoma in a third world country. AB - The treatment and prognosis of invasive cervical carcinoma depends on proper clinical staging. The prestaging investigations are time-consuming and costly and 3rd world countries find it difficult to adhere to 1st world protocols. In the search for a more cost-effective but safe protocol for pre-treatment investigation the analysis of some of the special investigations performed on a total of 903 patients with invasive cervical carcinoma have proven beyond doubt that some of these investigations can be omitted without harming the patient. The Gynecologic Oncology Unit of the Tygerberg Hospital R.S.A. propose such a cost effective protocol provided some criteria are strictly adhered to in safe guarding proper health care. PMID- 2898404 TI - Carcinoma of the cervix uteri in Zaria: etiological factors. AB - The study conducted at Ahmadu Bello University Teaching Hospital, Zaria from January to December, 1984 showed that carcinoma of the cervix uteri occurred in 4.18% of new gynecological attendances; 68.9% of the cases occurred in the age range 40-55 years. Early age at marriage (80.0%), and at first pregnancy (77.8%) as well as multiple marriages (48.9%) and low contraceptive usage were identifiable associated factors. The parity of the patient did not seem to be of significance. The earliest presenting symptom was post-coital bleeding occurring 10.8 months prior to attendance for medical advice. However, late presentation (in Stages IIb-IV) in 86.7% of cases was due to illiteracy, shyness, male dominance and non-recognition of the importance of early warning symptoms. PMID- 2898405 TI - The influence of different amounts of clomiphene citrate on follicle-stimulating hormone, luteinizing hormone and estradiol levels and on the number and maturation of follicles. AB - Sixty-eight anovulatory women were divided into three groups according to the administered doses of clomiphene citrate (CC) (A 250 mg, B 500 mg, C 750 mg). Daily follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) measurements were performed. Follicular maturation was monitored by ultrasound. In the high-CC dose group, a statistically significant FSH rise was noted. As a result, earlier selection of the dominant follicle (DF), faster increase in the DF diameter and increased E2 production was found. PMID- 2898407 TI - Puerperal adynamic ileus. AB - Puerperal adynamic ileus includes acute mild and severe clinical manifestations. Acute severe puerperal adynamic ileus may constitute the clinical indication of a serious underlying disease, such as sepsis, rupture of uterus, intra-abdominal or retroperitoneal bleeding, ureteral pathology, intra-abdominal foreign body and internal diseases. Sometimes the diagnosis requires abdominal and chest X-ray, uterine exploration and intravenous pyelography. Surgical treatment requires proper previous general evaluation; and fluids, electrolytes and plasma should be provided. PMID- 2898406 TI - Sonographic detection of an asymptomatic rupture of the uterus due to necrosis during the third trimester. AB - This is a report on the first sonographic detection of a silent rupture of the uterus in the 33rd week of pregnancy of a 35-year-old patient. On the basis of the clear sonographic picture immediate cesarean section was (considered) indicated in spite of lack of clinical symptoms. The intraoperative situs confirmed the sonographic diagnosis of a ruptured uterus related to an old cesarean section, combined with partial necrosis of the lower uterine segment. PMID- 2898408 TI - Estrogen treatment and subsequent pregnancy in two patients with severe hypergonadotropic ovarian failure. AB - The history, diagnosis and management of two patients with premature ovarian failure who responded to estrogen replacement therapy is presented. Both women conceived and had a live healthy baby. PMID- 2898409 TI - Testicular function in rats following immobilization stress. AB - Stress is believed to influence male reproductive activity. Male rats were subjected to immobilization stress for 2 h/day for 30 days to assess the effects of stress on testicular function. Net mass of the testes, epididymes and the seminal vesicles, sperm morphology, number of epididymal sperms and percent progressive motility of the sperms were determined. Adrenal weights were significantly increased (P less than 0.05) in the stressed animals. There was no significant difference between the control and the stressed animals with respect to testicular and epididymal weight, level of sperm production, progressive motility, seminal vesicular weight and abnormal forms. Histological examination also revealed a similarity in the structure of seminiferous tubules, adequacy of cell types of developing germ cells, structure of Leydig cells and epididymal lumina in both the groups. This study demonstrated a lack of significant effect of immobilization stress on testicular function in rats. PMID- 2898410 TI - Activation of four homeobox gene clusters in human embryonal carcinoma cells induced to differentiate by retinoic acid. AB - We have studied the expression of nine homeobox genes from Hox 1, Hox 2, Hox 3 and Hox 5 clusters in human embryonal carcinoma (EC) cell lines analyzed as both stem cells and after exposure to the differentiation-inducing agents retinoic acid (RA), hexamethylenebisacetamide (HMBA) and bromodeoxyuridine (BUdR). None of the homeobox genes was expressed in stem cells, whereas all were activated, although with different kinetics, in cultures of the pluripotent EC cell line NTERA-2, clone D1 (NT2/D1), following differentiation induced by RA. At least some homeobox genes were stably expressed in differentiated cells several weeks after removal of RA from the culture medium. However, the length of initial exposure to RA is a critical factor in achieving stable gene expression, and differs among the different sets of genes and, at least in one case, among different transcripts from the same gene. No homeobox gene expression was detected in NT2/D1 cells induced to differentiate with HMBA or BUdR. Also, no expression was detectable in xenograft tumors generated by NT2/D1 cells in nude mice, even though tumors of this type contain mostly differentiated cells. Other human EC lines tested, i.e., 833KE, 2102Ep or 1156QE, did not differentiate in response to RA and did not express homeobox genes. No expression was detectable in xenograft tumors of 833KE and 2102Ep, containing essentially EC cells. These data indicate that homeobox-gene activation specifically accompanies RA-induced differentiation of NT2/D1 cells, thereby providing an excellent model for studying the molecular basis of homeobox-gene regulation and the possible role of the homeobox in cell differentiation. PMID- 2898412 TI - [Short- and medium-term study of arterial grafts and native coronary circulation after in situ implant of the internal mammary artery]. AB - The internal mammary artery (IMA) is being increasingly utilized as a conduit for myocardial revascularization, based on its higher long-term patency. The aim of this study is the serial assessment of the changes of native coronary vessels after IMA coronary anastomosis. Twenty-six consecutive patients (24 males and 2 females, mean age 56.4 years) received an IMA graft on the left anterior descending (LAD) artery. IMA coronary anastomosis was single in 11 patients and double (LAD and diagonal branch) in the remaining 15 cases. In 23 patients (88.5%) at least one associated saphenous vein graft was inserted. Post operatively, no new Q waves or low-output syndromes were observed. Follow-up angiographic study, including selective opacification of the IMA graft, was carried out after 1 month and after 1 year. The cumulative patency rate of IMA grafts was 97.7% after 1 month. The LAD stenosis proximal to the IMA anastomosis progressed to total occlusion in 6 patients (28.5%), all of them with a preoperative stenosis ranging from 90 to 99%; its diameter remained unchanged in 6 patients (28.5%), while a reduction of the coronary narrowing greater than or equal to 20% was observed in 9 patients (43%). Preoperatively, the LAD stenosis of the latter groups ranged from 70 to 90%. Severity of residual stenosis and relative diameters of LAD artery and IMA graft influenced the competitive flow distribution through these vessels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898411 TI - Modulation of the hydrophobicity of glutamine synthetase by mixed-function oxidation. AB - Oxidative modification of Escherichia coli glutamine synthetase renders the enzyme susceptible to proteolytic degradation by a specific protease purified from the bacterium; native enzyme is not a substrate for the protease. A model oxidizing system consisting of ascorbate, iron, and oxygen was used to generate a series of glutamine synthetases of increasing oxidative modification. We assessed the effect of oxidative modification on the surface hydrophobicity of the glutamine synthetases, utilizing hydrophobic chromatography on a phenyl matrix. Initial exposure to the oxidizing system caused inactivation of the enzyme and generated a protein that was more hydrophilic than the native form; it was not a substrate for the protease. Continued exposure to the oxidizing system yielded a protein with additional oxidative modification. This form was distinctly more hydrophobic than the native form and it was very susceptible to proteolytic attack by the purified protease. Thus, oxidative modification modulates the surface hydrophobicity of glutamine synthetase, and this modulation can control susceptibility to proteolysis. PMID- 2898413 TI - [Effect of the sympathetic activation and its inhibition on left ventricular mechanics in mitral prolapse. Echocardiographic study in 35 patients]. AB - Mitral valve prolapse (MVP) is characterized by arrhythmias, atypical anginal chest pain and left ventricular (LV) wall motion abnormalities. The role of autonomic nervous system (ANS) as the origin of these disturbances is still debated. The aim of the study was to determine the possible interference between left ventricle (LV) mechanics and ANS. 35 consecutive patients with MVP (24 female, 11 male) (mean age 30 +/- 9 years), matched with a homogeneous control group, were examined by means of 2D-Echo during resting conditions and during sympathetic activation induced by passive orthostatism (90 degrees Tilting). At rest, no significant difference was found between the two groups regarding heart rate (HR), LV volume (LVV), ejection fraction (EF). Tilting produced a significant increase in HR (p less than 0.1) and LVV reduction (p less than .01) in both groups; on the other hand, EF did not change significantly. At 2D-Echo, LV abnormal wall motion at rest in 10/35 (29%) MVP, increasing to 17/35 (49%) was found during Tilting. This abnormality consisted in LV wall reduced systolic thickening and motion, localized in the antero-apical region in 11 patients (54%) and in the posterior wall in 6 patients (36%). Thirteen MVP patients with LV abnormal contraction patterns were re-examined after two weeks of beta-adrenergic blockade (200 mg Metoprolol orally per day). In all of them, LV abnormalities disappeared while LVV and EF remained unchanged. These data stress the role of the ANS in inducing LV abnormalities in patients with MVP. PMID- 2898414 TI - [Glaphenine biliary lithiasis. Identification by infrared spectrophotometry]. AB - The authors report the case of a woman, presenting with choledocholithiasis essentially composed of glafenic acid. Identification of the drug and its metabolites was demonstrated using infrared spectrophotometry and thin layer chromatography. To our knowledge, this is the first publication of drug choledocholithiasis. PMID- 2898415 TI - The bioelectrical activity of the body wall of the pulmonate freshwater snail Lymnaea stagnalis: effects of neurotransmitters and the sodium influx stimulating neuropeptides. AB - A method is described to dissect segments of the head skin of Lymnaea stagnalis. These skin segments were used to study the effects of neurotransmitters and of the Lymnaea sodium influx stimulating (SIS) peptides on ion transport, using the Ussing-cell technique. The electrical activity of the segments, with Lymnaea ringer solution at both sides, was low: the mean electrical potential difference (PD) across the skin was 0.7 +/- 0.6 mV (inside positive) at a resistance of 160 +/- 57 ohm.cm2 (inward short-circuit current, SCC, 4.2 +/- 3.0 microA/cm2; n = 25). Acetylcholine, adrenalin, noradrenalin, histamine, dopamine, and GABA, at 10(-5) M, did not affect skin resistance and PD. 5-Hydroxytryptamine-HCl (5-HT), however, in a dose-dependent way, increased the PD, SCC, and, to a much lesser extent, the resistance of skin segments. Extracts of the medium lip nerves, which contain the SIS peptides, had similar effects, but of much longer duration. Effects comparable to those of 5-HT and the SIS peptides could also be brought about by cAMP analogs. The inward current stimulation by 5-HT, SIS peptides, and cAMP was abolished by ouabain. The inward current induced by 5-HT and the SIS peptides was partly (10-25%) inhibited by amiloride. The presence of tetrodotoxin (10(-6) M) did not prevent the inward current stimulation by 5-HT and the SIS peptides. PMID- 2898416 TI - Molecular cloning and characterization of ovine homeo-box-containing genes. AB - The sheep genome contains at least eleven homeo-boxes (hox). Using two hox specific 36-mer oligodeoxynucleotides to screen a sheep genomic library, constructed in lambda Charon28, clones of nine of the hox were identified. Six of the hox clones were analysed by nucleotide sequencing, Southern-blot hybridization and Northern-blot analysis. Two of the hox appear to be cognates of the human Hu-1 (or mouse Hox 2.1) and the mouse Hox 1-3, while another is closely related to the mouse Hox 1-4. These results suggest that there is strong sequence conservation in the hox-containing genes of different mammals, and highlight the possible occurrence of an ubiquitous set of hox-containing genes in mammals. Northern-blot analysis of four sheep hox-containing genes indicates that they are all expressed during embryogenesis and that expression is temporally regulated allowing hierarchical-regulatory interaction. Interestingly, none of the cloned hox-containing sequences contain repetitive sequences. PMID- 2898417 TI - Neurohumoral mechanisms of aging. Symposium. October 14-16, 1986, Kiev. Proceedings. PMID- 2898418 TI - Age-related changes in brain neurotransmission. AB - In experiments on 2-, 10- and 22-month-old rats it was found that the Bmax values of dopamine (DA2), serotonin (5-HT1) and enkephalin (Enk) receptors as well as the 5-HT level in the three brain regions (cortex, striatum and hypothalamus) decreased with age; the DA level in the brain cortex and striatum and the noradrenaline (NA) content in the brain cortex decreased, while the NA level in the striatum and the 5-hydroxyindolacetic acid (5-HIAA) level in the brain cortex and the striatum as well as the MAO-T and MAO-A activities in the three brain structures increased. It is suggested that these and other changes observed in brain neurotransmission are an important element in the neurochemical bases of the age-related changes in behavior. PMID- 2898419 TI - Release of neurotransmitter amino acids from rat brain synaptosomes and its regulation in aging. AB - The release of neurotransmitter amino acids 14C-Asp, 14C-Glu and 14C-GABA from rat brain synaptosomes in aging is studied. It is established that K+-induced Ca2+-dependent and Ca2+-independent release of these amino acids decreases significantly in the old animals. K+ (40 mM) stimulates strongly their release for both ages, but the effect of K+ ions in old animals is less marked. Removal of Ca2+ has a greatly inhibitory effect on synaptosomal release in young as well as in old rats. The degree of inhibition does not depend on age, though it takes place at a lower level in old rats. PMID- 2898420 TI - Neurohumoral control of liver functions during aging. AB - A profound influence of steroidal (and possibly growth) hormone change during aging on the P-450 functions has been found in male rats. Direct and rapid autonomic nervous controls on glycogen metabolism in the liver is also greatly affected by aging. However, neither the responses of isolated rat hepatocyte preparations to adrenergic agonists nor the bindings of hepatocyte surface membrane preparations to adrenergic ligands was found to change with age, suggesting that the age effect on autonomic nervous control may be of central (presumably hypothalamic) origin. The present methodology of evaluating the receptor functions using Scatchard plot analysis does not seem sufficient to explore the functional alterations of receptor systems during aging and a need for new approaches that can determine certain physicochemical alterations of receptor, namely the measurement of the lateral mobility of membrane proteins during aging, is proposed. PMID- 2898421 TI - Laserlithotripsy of common bile duct stones. AB - Endoscopic retrograde laser lithotripsy of common bile duct stones is a new technique which can be carried out through the endoscope without anaesthesia using ordinary endoscopic equipment. In the method described here a flashlamp pulsed Neodymium YAG laser (wave length 1064 nm) was used. Light energy was transmitted along a highly flexible quartz fibre with a diameter of 0.2 mm. This new technique was used in nine patients with concrements in the common bile duct, which could not be removed with the established endoscopic techniques. In eight of the nine the concrements (maximum diameter 4.7 x 3.1 cm) could be fragmented and in six the fragments could be extracted from the common bile duct. The total energy required was 80-300 J; complications were not observed. PMID- 2898422 TI - Controlled trial comparing olsalazine and sulphasalazine for the maintenance treatment of ulcerative colitis. AB - One hundred and sixty four patients with ulcerative colitis in remission were entered into a double blind, double dummy trial comparing olsalazine 500 mg bd and sulphasalazine 1 g bd. Clinical examination, sigmoidoscopy and rectal biopsy were performed at 0, three, and six months. Sixteen of 82 (19.5%) patients relapsed on olsalazine and 10/82 (12.2%) relapsed on sulphasalazine. The difference was not statistically significant (p = 0.1632). Adverse events were minor and were similar in both groups. No haematological or biochemical abnormalities were detected. Thus, olsalazine is as effective as sulphasalazine for preventing a relapse of ulcerative colitis. PMID- 2898423 TI - Long acting somatostatin treatment of paraneoplastic Cushing's syndrome in a case of Zollinger-Ellison syndrome. AB - Cushing's syndrome, caused by ectopic ACTH production during Zollinger-Ellison syndrome, raises difficult therapeutic problems. We report a case of clinical and biological efficacy of long acting somatostatin (SMS) in this condition. In a short term study with 200 micrograms SMS bid, symptoms of hypercorticism disappeared while cortisol and ACTH serum concentrations fell below the normal values. Longterm treatment was instituted with 50 micrograms SMS bid. Excellent clinical efficacy as well as normal cortisol and ACTH serum concentrations were maintained during the nine month follow up. Lipotrophic hormone (LPH) serum concentration remained raised. No decrease in size of hepatic metastases was observed. Long acting somatostatin analogues may be useful in endocrine paraneoplastic syndromes. PMID- 2898424 TI - [Rational treatment of heart rhythm disorders. International symposium on "The Management of Cardiac Arrhythmias: the Role of Encainide and Sotalol". 24-25 March 1988, Wallingford (USA)]. PMID- 2898426 TI - Pancreatic secretagogues regulate somatostatin binding to acinar cell membranes via two-functionally distinct pathways. AB - Pretreatment of pancreatic acini with vasoactive intestinal peptide (VIP) or secretin for 120 min reduced subsequent [125I-Tyr1]somatostatin binding to membranes prepared from these acini, with a maximally reduced binding being 79.2% or 77.4% of control, respectively. In addition, exogenously added cyclic AMP derivatives or a phosphodiesterase inhibitor mimicked the effect of VIP or secretin. Scatchard analysis of [125I-Tyr1]somatostatin binding demonstrated that the decrease in the labeled somatostatin binding induced by VIP or dibutyryl cyclic AMP (dbcAMP) pretreatment was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. The effect of simultaneous pretreatment of acini with VIP and carbamylcholine (carbachol) on subsequent labeled somatostatin binding appeared to be almost equal to the calculated additive value for each peptide. Results obtained, therefore, indicate that the binding of somatostatin to its receptors in the pancreas may be regulated via two functionally distinct pathways. PMID- 2898425 TI - [Studies on the clinical significance concerning the changes in serum pepsinogen I and gastrin levels in aged patients with chronic gastritis]. AB - Of 86 cases of aged patients with chronic gastritis treated with Trimebutine or Flutazolam, we evaluated the changes of serum pepsinogen-I and gastrin levels in their clinical courses from the points of the correlation with severity of chronic gastritis, aging phenomenon and the changes of symptom and endoscopic findings. In order to elucidate the multidimensional interrelation among these items, we used Hayashi's quantification theory II as a conventional analysis method. In aged patients, generally, although the serum gastrin levels were rather high compared with younger generation, the serum pepsinogen-I levels were consistently low throughout their clinical courses. There were some correlation between the levels of serum gastrin and the severity of chronic gastritis. When the drugs were effective on improving the condition of the disease, the level of gastrin revealed gradual decrease. These changes of gastrin were more typical in patients treated with Trimebutine. PMID- 2898427 TI - Postprandial glycaemic effects of a long-acting somatostatin analogue (octreotide) in non-insulin dependent diabetes mellitus. AB - Postprandial changes in blood glucose, insulin and glucagon were examined in 7 non-insulin dependent diabetic patients, before and after 3 days' treatment with the somatostatin analogue, octreotide (50 ug injected subcutaneously thricedaily). After octreotide injection, postprandial rises in plasma insulin and glucagon were significantly flattened. The postprandial glycaemic rise was delayed but the area under the glycaemic curve was not increased. Animal studies have suggested that octreotide inhibits growth hormone and glucagon secretion much more powerfully than native somatostatin, while relatively sparing insulin secretion. However, the present findings suggest that this analogue is not sufficiently selective to be therapeutically useful in non-insulin dependent diabetes. PMID- 2898428 TI - Seven polymorphic loci mapping to human chromosomal region 11q22-qter. AB - Seven polymorphic loci that map to human chromosomal region 11q22-qter are revealed by DNA probes isolated from a chromosome-specific phage library constructed from a human X mouse somatic cell hybrid that has retained an 11q;16q translocation as the only human DNA. Three probes, each of which reveals a two allele polymorphism, and four probes, each of which detects two linked RFLPs, have been characterized. Using a somatic cell hybrid mapping panel that divides 11q into four discrete sections, the seven clones have been localized to specific chromosomal regions. Localization of one of the clones has been confirmed and refined by in situ hybridization. PMID- 2898429 TI - Proteins that appear to be associated with pili in Neisseria gonorrhoeae. AB - Pili of Neisseria gonorrhoeae are thought to be composed entirely of identical subunits, called pilin, that self-assemble in vitro. Previous pilus purification methods have relied on this latter point, and dissociation and reassociation of pilin subunits has yielded pilin preparations of high purity. Such a procedure could result in the loss of any pilus-associated proteins. We have developed a procedure for the isolation of intact native pili in a deoxycholate-urea buffer in which the pili are fractionated on the basis of size and hydrophobicity. Electron microscopy indicates that the pili are largely free from outer membrane vesicles and other cellular material. Electrophoretic analysis has shown that a number of proteins copurify with pilin. Antibodies to these proteins could be removed from an antiserum against whole piliated cells by absorption with piliated cells but not by absorption with nonpiliated cells. Hence, our results indicate that these proteins could be pilus associated. PMID- 2898432 TI - Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. I. Watchkeeping on board ships: a methodological approach. AB - The safety of a ship depends substantially on its bridge watchkeepers, whose alertness and efficiency must be maintained at all hours of the day and night. Fatigue, circadian rhythms, and sleep disruption occasioned by the unusual working hours of these personnel may all affect their performance. A methodology for assessing the magnitude of this problem is proposed. The application of this methodology in a large-scale shipboard study of merchant mariners on extended voyages is then described, and details given of the techniques used to measure sleep and activity, and temporal variations in a range of physiological und psychological parameters. A summary of the data collected in the study is provided as a reference point for the reports on the different aspects of the results that follow in subsequent articles. PMID- 2898430 TI - Mediation of immunity to Eimeria vermiformis in mice by L3T4+ T cells. AB - Immunity to infection with Eimeria vermiformis was transferred in NIH mice by both the nylon wool-adherent (B-cell-enriched) and nonadherent (T-cell-enriched) fractions of lymphocytes (spleen and mesenteric lymph node) taken from infected donors. Transfer was more variable with the adherent fraction, and when contaminating T cells were removed by treatment with anti-Thy1 monoclonal antibody (MAb) and complement, this fraction lost all protective activity. The protective effect of T-cell-enriched populations of mesenteric lymphocytes was abrogated by treatment with anti-L3T4 MAb and complement in vitro before transfer or by opsonization with this MAb in vitro before intravenous inoculation into recipients. Similar treatments of cells with anti-Lyt2 MAb did not have this effect, confirming that Thy1+ L3T4+ cells mediate the adoptive transfer of immunity to E. vermiformis. Thy1+ L3T4+ cells were also shown to limit the replication of E. vermiformis in primary infections: mice depleted of this subset (by thymectomy followed by intravenous injection of anti-L3T4 MAb) passed greater numbers of oocysts over a longer period of time than did mice similarly depleted of Lyt2+ cells. PMID- 2898431 TI - Epidemiological study on the hepatotoxicity of occupational toluene exposure. AB - In a cross-sectional study of 181 male workers of a rotogravure printing plant, most of whom were exposed to toluene levels well above the GDR threshold limit values, 55 subjects revealed pathological liver screening values (activities of serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase; liver size). The differential diagnostic examination showed in 51 out of these 55 subjects an association with competing factors such as alcohol abuse (78%) and overweight (40%), to a slight extent disorders of fat and carbohydrate metabolism and of the gallbladder. Drug intake did not play any role. The variance and regression analyses of the biochemical data have shown that alcohol significantly and considerably increases the activities of all three enzymes tested. Bodyweight had a similar, but less pronounced, significant effect. On the other hand, in subjects with a higher alcohol intake the activities of liver enzymes in highly toluene exposed subgroups were significantly and clearly lower than among slightly toluene exposed workers. PMID- 2898433 TI - Clinical pharmacology of intravenous induction drugs. PMID- 2898434 TI - The prevalence and transmission of hepatitis B virus infection in urban, rural and institutionalized black children of Natal/KwaZulu, South Africa. AB - The sera of statistically selected urban (805), rural (238) and institutionalized (127) black children were tested for markers of hepatitis B virus (HBV) infection. The age-standardized (6-14 years) prevalence rates of HBs antigenaemia for comparison between urban, rural and institutionalized children were 10%, 18.5% and 25.1% and the HBV exposure rates were 31.4%, 62.1% and 72.0% respectively. In the newborn to six years age group the prevalence rates of HBsAg and HBV exposure were 2.5% and 7.1% for urban children and 53.1% and 70.3% for institutionalized children. Peak prevalences of HBsAg occurred in the 6-8 year age group and were 14.4% and 22.6% in urban and rural children respectively. Hepatitis Be Antigen (HBeAg) was detected in 46.5% and antibodies to hepatitis Be antigen (HBeAb) in 10.0% of all HBsAg positive children. Multiple mechanisms involving horizontal rather than vertical transmission appeared to be important in urban children, with HBV exposure in females being significantly associated with ear-piercing (p less than 0.001) and scarification (p less than 0.05). In addition, HBsAg was detected in 25 of 29 pools of bloodfed mosquitoes caught at the children's institution and was negative in all four pools of unfed mosquitoes, suggesting that these arthropods may also be one factor in the horizontal spread of HBV infection. Familial clustering of HBV infection was suggested by a significantly higher (p less than 0.01) prevalence of HBsAg amongst family contacts of HBsAg positive urban children (17.7%) than in the control groups of family contacts of HBsAb positive children (8%) and children who were negative for all HBV markers (2.4%). The significance and implications of these findings are discussed. PMID- 2898435 TI - Laparoscopy in the diagnosis and treatment of pelvic inflammatory disease: a review and discussion. PMID- 2898436 TI - Hydralazine-induced hepatitis in pregnancy. AB - During 1983, 38 patients with pregnancy-induced hypertension were treated with hydralazine-apresoline (1-hydrazinophthalazine). During the course of their treatment, five of these patients showed evidence of the HELLP syndrome described by Weinstein (hemolysis, thrombocytopenia, and elevated liver enzymes). Evidence is presented on the role of hydralazine in producing hepatocellular damage. Liver function is compromised during the natural course of pregnancy-induced hypertension, and 5-10% of preeclamptic patients develop the HELLP syndrome. In many places hydralazine is the drug of choice in the treatment of pregnancy induced hypertension. PMID- 2898437 TI - Mycoplasma, chlamydia, Epstein-Barr, herpes I and II, and AIDS infections among 100 consecutive infertile female patients and husbands: diagnosis, treatment, and results. AB - One hundred consecutive infertile patients were studied to determine the incidence of sexually transmitted diseases (STDs) among middle and upper income patients, most of whom were referred as longstanding failures by other physicians. There were no cases of syphilis, gonorrhea, or AIDS found among these patients. One patient was pregnant when first seen, and was eliminated. Genital mycoplasmas were cultured from 64 wives. Antibodies for past or recent infection with Chlamydia were present in only 23. Antibodies to Epstein-Barr virus and to herpes II were found in 92 and 65, respectively. If only the mycoplasmas, Chlamydia, and herpes II are considered possible causes of human infertility, only 7 of the 99 couples showed no evidence of ever having had any of these three infections. Edometrial histology was positive for the changes associated with Mycoplasma infection in 47 of the 86 patients biopsied. Of the 39 with negative biopsies, 24 yielded positive cultures for Mycoplasma. Hence, only 15 of the 99 patients were negative for Mycoplasma by both culture and/or endometrial histology. Treatment with the antibiotic of choice, as indicated by sensitivity testing of all Mycoplasma-positive cultures, was an important factor in producing 43 pregnancies during the first year of study. Two of these were ectopic; 11 were spontaneous abortions, with one of these women now pregnant again and in mid trimester; 28 have delivered healthy babies; and two are still pregnant and doing well. PMID- 2898438 TI - Diagnosis and treatment of the cervical factor. I. Improvement with a short course treatment of high-dose estrogen. AB - A new technique for improving cervical factor is described. This technique employs the use of high-dose estrogen at the time that a mature follicle is determined by ultrasound in patients who have inadequate postcoital tests despite the use of low-dose estrogen, guaifenesin, and tetracycline. Previously, a technique based on high-dose estrogen early in the follicular phase was employed; this suppressed pituitary gonadotropins, thus requiring the concomitant use of hMG. Seventy-three percent of the patients for whom this more expensive and intricate technique would have been necessary were able to achieve a good postcoital test through this modified technique of merely using high-dose estrogen when the follicle has already matured. Thirty-three percent achieved a pregnancy within 6 months on this therapy. PMID- 2898439 TI - Diagnosis and treatment of the cervical factor. II. Employment of pelvic sonography in diagnosis. AB - A study was performed to evaluate the relationship between the postcoital test, follicle size, and the basal body temperature (BBT). We found 17% of the patients to have good postcoital tests before the rise in the BBT, at which time, however, the follicle was still too small. By the time the follicle reached maturity, the mucus quality regressed to poor. The problem was corrected in 88% of the patients by the human menopausal gonadotropin (hMG)-high-dose estrogen technique, and 53% achieved pregnancies. Twenty-two percent had a poor postcoital test just before the rise in the BBT. However, ultrasound data indicated that ovulation had already taken place, and the mucus had been of good quality a few days before, when the follicle was at the proper size. Thus, ultrasound may be useful in eliminating false positive and negative cervical factor diagnoses, and is also helpful in some new techniques for treating the cervical factor. PMID- 2898440 TI - Failure of uterine withdrawal bleeding following exogenous estrogen and progestin administration. AB - A woman who showed no secretory effect on repeated endometrial samplings, in the absence of Asherman's syndrome on hysteroscopy, conceived on clomiphene administration. The possibility of uterine progesterone receptor decreases in number or affinity as a cause of improper histologic response to endogenous hormone production is discussed. PMID- 2898441 TI - Luteal phase deficiency: an inadequate endometrial response to normal hormone stimulation. AB - Two hundred seventy-four infertile patients and 43 women with two or more previous first-trimester abortions underwent a luteal function evaluation by basal body temperature, plasma progesterone, estradiol and prolactin determination, and endometrial biopsy (repeated in a later cycle when the first was defective). An endometrial luteal phase deficiency was detected in 37 (13.5%) of the infertility cases and in 14 (32.5%) of the patients with recurrent miscarriage. However, the endometrial defect was associated with normal hormonal levels in the great majority of patients (86.3%). PMID- 2898442 TI - Cleavage rate of embryos in the rabbit oviduct following tubal surgery. AB - The effect of tubal surgery upon early embryonic development in the rabbit oviduct was studied. Resection-reanastomosis was performed applying microsurgical techniques. Embryonic cleavage stages were recorded in the surgically altered oviduct, in the contralateral nonoperated tube, and in the tubes of nonoperated control animals. Higher cleavage rates were found in the operated animals compared with nonoperated controls. Early embryonic development was enhanced in both the operated tube and the contralateral nonoperated tube. These findings suggest an embryonic cleavage promoting factor to be active in the operated animals. This factor seems to affect not only the operated tube, but the contralateral control tube as well. PMID- 2898443 TI - Sperm penetration in capillary tubes with albumin-Ringer solutions. AB - Linear penetration of sperm from 65 different semen samples was investigated in Ringer solutions containing 1%, 3%, and 6% bovine albumin and in cervical mucus by use of the capillary tube test. A high degree of correlation was observed between the penetration distances recorded in the Ringer-albumin solutions, particularly in the 3% and the 6% solutions, as compared with those observed in cervical mucus. The relative number of spermatozoa with abnormal configuration was found to be markedly lower in the upper segment of the tubes, indicating a relationship between propulsive motility and normal morphology. PMID- 2898444 TI - The effect of serum prolactin levels on ovarian steroidogenesis. AB - In order to assess the effect of hyperprolactinemia on ovarian steroidogenetic potential, a group of anovulatory hyperprolactinemic patients and a control group of anovulatory normoprolactinemic women were submitted to exogenous gonadotropin (hMG) stimulation under identical experimental conditions. Serum 17 beta estradiol (E2) concentrations were determined before and after hMG stimulation. The mean basal serum E2 levels in the hyperprolactinemic group (22.7 +/- 3.3 pg/mL, mean +/- 1 SE) were significantly lower than in the normoprolactinemic control group (48.7 +/- 8.4 pg/mL, P less than .01). A significant negative correlation (r = -.6157, P less than .01) between basal serum E2 levels and basal serum prolactin (hPRL) concentrations was found. Following hMG stimulation, the serum E2 increment (delta E2) from basal E2 levels in the control group (491 +/- 91 pg/mL) was significantly higher than the increment in the hyperprolactinemic group (182 +/- 48 pg/mL, P less than .01), and a significant negative correlation was observed between basal serum hPRL levels and the logarithm of delta E2 (r = .4744, P less than .05). Our results suggest that chronic hyperprolactinemia induces ovarian refractoriness to exogenous gonadotropin stimulation and substantially reduces its steroidogenetic potential. PMID- 2898445 TI - Second World Conference on Fallopian Tube in Health and Disease. January 27-31, 1987, Dorado Beach, Puerto Rico. Abstracts. PMID- 2898446 TI - Ovulation in uremic women: the reproductive cycle in women on chronic hemodialysis. AB - We studied five uremic women of fertile age and on chronic intermittent haemodialysis over a 3-month period. The purpose of this investigation was to establish how often the hormonal pattern indicated ovulation in uremic women and, thereby, the possibility of an inexpedient pregnancy. The pituitary ovarian axis was estimated by analyzing the serum concentrations of follicle-stimulating hormone, luteotropic hormone, progesterone, estradiol, and prolactin. Forty percent of the investigated cycles seemed to be ovulatory, though with a slightly atypical hormonal pattern. Because of these factors, it is recommended that sexually active women of fertile age and on chronic intermittent hemodialysis consider the use of contraception in order to avoid unwanted pregnancies. PMID- 2898447 TI - Distal tubal occlusion: microsurgery versus in vitro fertilization--a review. AB - The success of in vitro fertilization (IVF) has established it as a viable alternative in the treatment of infertility associated with distal tubal occlusion (DTO). In an attempt to adequately counsel patients with DTO as to whether their primary treatment should be microsurgery or IVF, the authors have performed a comprehensive world-wide literature review. Based on what has been published to date, it would appear that patients with mild to moderate tubal disease should be offered salpingoneostomy as their first treatment modality. For patients with severe disease accompanied by extensive pelvic adhesions, salpingoneostomy should be discouraged. PMID- 2898449 TI - Ovulation induction for in vitro fertilisation using clomiphene citrate and low dose human menopausal gonadotrophin. AB - Ovulation induction using a low dose of human menopausal gonadotrophins and clomiphene citrate for in vitro fertilisation and embryo transfer is described. Sixty-two cycles of ovulation induction were initiated in 37 patients. Forty-six laparoscopies were performed, yielding 116 oocytes. Of these, 90 (77.6%) cleaving embryos developed, and in 36 transfers 10 pregnancies (27.8%) were established. The use of low-dose hMG in conjunction with a programme on an outpatient basis may prove to be optimal for the purpose of in vitro fertilisation and embryo transfer. PMID- 2898448 TI - Nonsurgical management of unruptured isthmic ectopic pregnancy: preliminary experience. AB - Five unruptured isthmic tubal pregnancies diagnosed at laparoscopy were treated with either methotrexate/citrovorum factor rescue (MTX/CF) (n = 4) or observation alone (n = 1). Entry criteria required that the ectopic be fully visualized, no greater than 3 cm in diameter, with intact serosa, and without active bleeding. Treatment selection was based upon preoperative levels of beta-hCG with MTX/CF given to subjects exhibiting a plateaued or rising pattern and observation alone given those with falling levels. Subjects were followed with serial measurements of beta-hCG, complete blood counts, and liver function tests. In all subjects the ectopic pregnancy resolved without further surgery. Time to resolution (first day of treatment to undetectable beta-hCG) ranged from 12 to 55 days. Of the five subjects studied, follow-up hysterosalpingograms in four demonstrated tubal patency on the side of the ectopic gestation. PMID- 2898451 TI - Reproductive performance of dibromochloropropane-treated female rats. AB - Dibromochloropropane (DBCP) is an effective nematocide which has been shown to suppress spermatogenesis and cause infertility in both men and male rats. There are no similar reports concerning the effects of DBCP on female reproduction. The purpose of the present study was to attempt to interfere with the various phases of oogenesis. Proestral or pregnant rats were injected subcutaneously once with 40 mg/kg DBCP on one of each days of L12-L20 of gestation; a double dose (80 mg/kg) was injected in eight consecutive days (L11-L18). In addition, L13 fetuses were injected--directly into the amniotic sac--with 0.1 mg DBCP. Pooled data from the various days of gestation revealed that postimplantation losses were three times as high in the DBCP-treated animals as in DMSO-treated controls. Perinatal deaths were 58% higher and mean pup weights were 30% lower in the DBCP-treated rats than in controls. The reproductive performance of females exposed to DBCP while in utero was affected only to a limited degree (reduced number of ovulations and implantations) as compared with their DMSO counterparts. Doubling the dose (80 mg/kg) seriously reduced the birth weight of pups (50% of controls), all of which died within several hours post-partum. Direct injection of DBCP into embryos or to proestral rats did not have any adverse effects on their future reproductive performance. In contrast to the effect on spermatogenesis, it appears that oogenesis and ova are unaffected by DBCP. PMID- 2898450 TI - Effects of momorcharins on ovarian response to gonadotropin-induced superovulation in mice. AB - Alpha- and beta-momorcharins, which are abortifacient proteins isolated from Momordica charantia seeds, were tested for a possible effect on ovulation and plasma levels of ovarian steroids in mice induced to superovulate by PMSG and hCG. The plant proteins did not affect follicular recruitment and maturation as evidenced by ovarian histology and serum 17 beta-estradiol level. Both proteins diminished the number of oocytes ovulated when given on the day prior to or on the day of PMSG treatment, but not when given after the gonadotropin injection; they also increased the incidence of follicular atresia. The number of corpora lutea was slightly reduced by treatment with the proteins, but there was no long term suppression of the serum progesterone level. After mating, animals which have previously been treated with the plant proteins underwent pregnancy resulting in a litter size similar to that of controls. PMID- 2898452 TI - Maturation of bovine oocytes transplanted into bovine follicles of follicular and luteal phase. AB - Forty-one bovine host follicles with guest oocytes were studied. Fifty of these host follicles from the follicular phase and 26 follicles from the luteal phase of the cycle were cultured in a continuous flux system. No hormones were added to the follicular fluid or the culture medium. After culturing there was no close contact between the oocyte complex and the follicular wall. Of the oocytes cultured in the follicular-phase follicles, 27.2% remained in the germinal vesicle stage and 7.1% reached MII, whereas 9.9% of the oocytes cultured in the luteal-phase follicles remained in germinal vesicle phase and 29.5% reached MII. Of the oocytes cultured in the luteal-phase host follicles, 15.2% were fertilized in vitro; none of the oocytes cultured in follicular-phase follicles were fertilized. PMID- 2898453 TI - Effects of progesterone on postoperative adhesion formation in hysterectomized rabbits. AB - Progesterone has been reported to have an antiinflammatory as well as immunosuppressive effect, and may prevent adhesion formation. In this study, nine treated and seven control rabbits were randomly selected for either pre- and postoperative progesterone treatment or no treatment. All rabbits underwent hysterectomy, focal peritoneal denudation, and intraabdominal instillation of suspended talc. Adhesion formation was evaluated 1 month postoperatively during repeat exploratory laparotomy. Progesterone-treated and control rabbits did not show any significant difference overall in the incidence of adhesion formation. Subgrouping of adhesion formation into adhesions formed by major surgical tissue trauma or minor peritoneal damage revealed a beneficial effect of progesterone in the reduction of only minor adhesion formation. PMID- 2898454 TI - In memoriam Robert B. Greenblatt. PMID- 2898455 TI - Gonadotropin therapy: new trends and insights. PMID- 2898456 TI - The diagnostic value of hysterosalpingography and laparoscopy in infertility investigation. AB - Four hundred and twenty infertile patients had hysterosalpingography (HSG) and laparoscopy as a part of their infertility workup. A comparison of HSG and laparoscopy findings was carried out to study the diagnostic value of each of these two procedures. It was found that the accuracy in the diagnosis of tubal patency or tubal blockage was quite similar for both procedures. However, laparoscopy revealed peritubal adhesions in 29.8% of patients, whereas HSG made an accurate diagnosis in only 8.8%. It is concluded that HSG is as accurate as laparoscopy in the diagnosis of tubal patency or blockage, and should remain an integral part of female infertility investigation. Laparoscopy excels HSG in the diagnosis of pelvic pathology and thus should always be performed whenever a pelvic factor is suspected in female infertility. PMID- 2898457 TI - The effects of a new beta-adrenoceptor agonist BRL 26830A in refractory obesity. AB - Beta-adrenoceptor agonists have recently been shown to promote substantial loss of adipose tissue in laboratory animals. One of these BRL, 26830A, increases thermogenesis in human volunteers and has been shown to enhance the rate of weight reduction in patients adhering to a strict reducing regimen. Forty-three post-menopausal or sterilized female subjects suffering from refractory obesity participated in a double-blind placebo-controlled study, the treatment group receiving BRL 26830A 50 mg qid. Two subjects were withdrawn because they developed an unpleasant sensation of tremor and in all, 17 of the 20 who received BRL 26830A mentioned this side effect. There was no change in erect or supine blood pressure or in resting heart rate. There was no significant difference in weight change during the 6-week study. It is concluded that BRL 26830A does not appear to promote weight reduction in subjects unable to adhere strictly to their dietary regime. PMID- 2898458 TI - Efficient conjugation of DTPA to an IgM monoclonal antibody in ascites fluid. AB - We have developed a simple, rapid, and reproducible method for conjugating the bifunctional metal chelator diethylenetriaminepentaacetic acid (DTPA) to an IgM monoclonal antibody (MoAb) without first isolating the MoAb from the ascites fluid. Treatment of the protein mixture in the ascites fluid with cyclic DTPA anhydride (cDTPAA) followed by HPLC purification on a size exclusion column allowed isolation of the DTPA-IgM conjugate which could then be labeled with 111In in greater than or equal to 80% yield. Over the range of total protein concentrations used (11-44 mg/mL), the number of DTPA molecules per molecule of IgM was approximately one-half the molar ratio of cDTPAA to total protein. We have used this method to prepare an 111In labeled anti-Thy 1.2 IgM, a MoAb with specificity for a murine cell-surface antigen found on normal and malignant T cells and neuroectodermal tissues. Analysis of the DTPA-IgM conjugate prior to and after 111In labeling using indirect immunofluorescence flow cytometry and a target-cell binding assay showed that the antigen specificity of this anti-Thy 1.2 MoAb is not substantially altered by the presence of up to 8 DTPA molecules per IgM molecule. PMID- 2898460 TI - Evidence of the African origin of sickle cell hemoglobin in western Sicily. PMID- 2898459 TI - Non-random association of the Rsa I polymorphic site 5' to the beta-globin gene with major sickle cell haplotypes. AB - There are three main African haplotypes associated with the sickle mutation on chromosome 11. We have examined an Rsa I polymorphism 550 bp 5' to the beta globin gene to study the degree of linkage disequilibrium between this Rsa I site and the three haplotypes. This Rsa I site is contained within the 10.3 kb or less area of randomization separating the 5'- and 3'-haplotype clusters. The beta S containing chromosomes of the Benin and Senegal haplotypes are not cut, while those of the Central African Republic are cleaved by Rsa I at this site. Possible explanations of these findings are discussed. PMID- 2898461 TI - Selected allied health professionals' self-confidence in health promotion counseling skills and interest in continuing education programs. AB - Mail surveys of samples of dental hygienists (n = 90, 36% response), registered dietitians (n = 262, 52% response), and physician assistants (n = 289, 89% response) in Texas and certified nurse midwives (n = 143, 57% response) in the US provided data regarding their confidence that they possess skills and knowledge to counsel patients about selected areas of health promotion (self-efficacy). Also, the surveys gathered information regarding respondents' beliefs that patients will follow through on their recommendations (adherence expectation), and their interest in continuing education programs. Overall, respondents displayed highest self-efficacy with regard to counseling patients about blood pressure and smoking. Confidence was lowest in illicit drug abuse and mental health areas. Certified nurse midwives and physician assistants indicated confidence in many more areas than the other two groups. Respondents consistently expressed less certainty about patient adherence than about their own skills and knowledge. They generally indicated a high degree of interest in continuing education across the several health promotion topics. Modest relationships were observed between self-efficacy and interest in continuing education programs for physician assistants and registered dietitians, indicating that those with greater self-efficacy had a greater interest in building their skills. A similar pattern was observed among physician assistant respondents with respect to adherence expectations. PMID- 2898462 TI - A computerized approach to discipline-specific bibliographies in the allied health sciences. AB - The traditional subject headings in Index Medicus and other standard indexes have frequently proved too broad for researchers in the allied health sciences. Therefore, the Physician Assistant Program at the University of Florida has developed a computerized bibliography program designed to expedite research by using a selected list of keywords as subject headings and subheadings tailored to the interests and concerns of the physician assistant profession. Each subject heading and subheading is translated into a numerical coding system that permits efficient data entry and rapid identification of items in the professional literature as well as reducing the incidence of operator error in data entry. The program can be used for review of the literature, curriculum design, identification of supplementary reading material for education courses, and identification of appropriate resources to enhance the study of the physician assistant profession. Through the development of discipline-specific keywords, the program can be tailored to the educational and research interests of any discipline in the allied health sciences or other educational fields. PMID- 2898463 TI - Defective human immunodeficiency virus (HIV) particles produced by cloned cells of HTLV-I-carrying MT-4 cells persistently infected with HIV. AB - Persistently HIV-infected cell lines were isolated from surviving and proliferating cells after infection of HTLV-I-carrying MT-4 cells with cell-free human immunodeficiency virus (HIV); HTLV-IIIB and LAV. The media of the cloned cell cultures did not cause HIV infection of MT-4, MOLT-4, TALL-1, or HL-60 cells. Most of the constituents of the virus in the media were env proteins and many defective doughnut-shaped particles released from the cells were identified by electron microscopy. PMID- 2898464 TI - A soluble-factor(s) secreted by a human skin cancer cell line supports clonal growth of adult T-cell leukemia cells. AB - Leukemic cells from four out of eight patients with adult T-cell leukemia (ATL) were successfully grown by cocultivation with HSC-I cells, a human skin cancer cell line, in the presence of interleukin-2. Three of these four cultures of growing cells showed rearrangement of the T-cell receptor beta-chain gene like the original leukemic cells in vivo, and also showed conservation of the patterns of HTLV-I integration of the original leukemic cells in vivo. Cell-to-cell contact between HSC-I cells and leukemic cells was not necessary for growth of the leukemic cells. The results indicate that some soluble growth factor secreted by HSC-I cells and interleukin-2 are required for the in vitro growth of leukemic cells from some patients with adult T-cell leukemia. PMID- 2898465 TI - Enzyme-altered liver cell foci in woodchucks infected with woodchuck hepatitis virus. AB - The histochemical characteristics of liver cell foci in woodchucks were investigated. The foci appeared to be distributed throughout the liver and were observed only in the woodchuck hepatitis virus (WHV)-positive animals, including all 19 woodchucks with hepatocellular carcinoma(HCC), and 7 without HCC. No foci appeared in 11 WHV-negative animals. Histochemical studies revealed that liver cell foci and carcinoma cells were characterized by positive gamma-glutamyl transpeptidase (GGT) enzymatic reactions and decreased glucose-6-phosphatase enzyme activity compared to non-neoplastic liver. Furthermore, serum GGT was significantly elevated in almost all of the animals which had larger carcinomas. Ultrastructural findings of foci showed some resemblance to carcinoma cells, being characterized by abundant free ribosomes within the cytoplasm and undeveloped endoplasmic reticulum. These results suggest that the liver cell foci are potential precursors of HCC in WHV-infected animals, and that serum GGT may be a useful marker for indicating the development of carcinoma. PMID- 2898467 TI - Three tests of the hypothesis that glutamate is the sensory hair cell transmitter in the frog semicircular canal. AB - Three series of experiments were devised to test the hypothesis that glutamate is the transmitter released by sensory hair cells of the frog semicircular canal. These three tests were: 1 - The Tolerance experiment (i.e. making the preparation tolerant to injected Glu yet still capable of responding to endogenous transmitter). 2 - The Glu Decarboxylase experiment (i.e. bathing the preparation in sufficient enzyme to prevent the effects of exogenous Glu by degrading it without affecting the response to endogenous transmitter) and; 3 - The Diltiazem experiment (i.e. using the calcium channel antagonist, diltiazem, to prevent the effect of exogenous Glu and yet not to interfere with endogenous transmitter release and action). The Tolerance and Diltiazem experiments produced results indicative of a clear dissociation between exogenous Glu and natural transmitter. The Glu decarboxylase experiment results were not so clear, producing both evidence for and against the hypothesis. PMID- 2898466 TI - HCG treatment increases intratesticular pressure in the abdominal testis of unilaterally cryptorchid rats. AB - Adult, unilaterally cryptorchid rats were given a single subcutaneous injection of hCG. HCG treatment of 100 I.U. (but not 10 I.U.) resulted in a marked increase in intratesticular pressure (approximately 40 mm Hg) in the abdominal testis that was maximal 24 hours after treatment. This increase in pressure is caused by increased vascular permeability coupled with insufficient lymph drainage. In the scrotal testis, hCG treatment resulted in increased vascular permeability and lymph flow, but this did not result in a marked increase in testicular pressure. No morphologic signs of hCG-induced damage were observed in either the abdominal or scrotal testis 10 days after hCG treatment. Testicular microcirculation, as studied by laser doppler flowmetry, was abnormal in the abdominal testis, but hCG treatment inhibited vasomotion in both the abdominal and scrotal testis. PMID- 2898468 TI - Ultrastructural localization of GABA-immunoreactive terminals in the anteroventral cochlear nucleus of the guinea pig. AB - The immunocytochemical distribution of gamma-aminobutyric acid (GABA) was studied by electron microscopy in the anteroventral cochlear nucleus (AVCN) of the guinea pig using affinity-purified antibodies made against GABA conjugated to bovine serum albumin. Our observations confirm that spherical cells are the predominant cell type in the guinea pig AVCN and receive numerous axosomatic contacts (Schwartz and Gulley, (1978) J. Anat. 153, 489-508). Stellate cells receive few axosomatic contacts. Electron microscopic immunocytochemistry shows that GABA immunoreactivity is present in synaptic terminals in the AVCN. Of the several classes of presynaptic terminals present in the AVCN as characterized by vesicle type (large round; oval/pleomorphic; flat; small round) only those containing oval/pleomorphic vesicles were GABA-immunoreactive. However, GABA immunoreactivity may not be present in all these terminals because some oval/pleomorphic terminals are unlabelled. Immunoreactive terminals are widespread in the AVCN; they are abundant on spherical cell bodies, rarely seen on stellate cell bodies and are also found scattered throughout the neuropile. PMID- 2898469 TI - Simplified methods for the microbiological evaluation of bottled natural mineral waters. AB - The conventional methods for the microbiological examination of natural mineral water were compared with a simplified procedure. The results indicate that when indicator micro-organisms are present in water, they may not be detected in the simplified method. An alternative procedure, including the determination of Pseudomonas aeruginosa, is suggested. PMID- 2898470 TI - Genetic analysis of a region of the Bordetella pertussis chromosome encoding filamentous hemagglutinin and the pleiotropic regulatory locus vir. AB - The vir locus of Bordetella pertussis apparently encodes a trans-acting positive regulator that is required for the coordinate expression of genes associated with virulence: pertussis toxin, filamentous hemagglutinin (FHA), hemolysin, and adenylate cyclase toxin. DNA clones of vir and of genes required for the synthesis of some of the factors under vir control were obtained with DNA probes from the chromosomal DNA surrounding sites of Tn5 insertion mutations that inactivated those genes. Two vir clones were found which also contained genes required for the proper expression of FHA in B. pertussis. The plasmids which contained both the fha and vir genes expressed immunologically reactive FHA in Escherichia coli, as detected by colony blots, whereas plasmids which contained only fha or vir were negative in this assay. The regulation of FHA production in E. coli, as in B. pertussis, was temperature dependent and inhibited by high concentrations of either magnesium ions or nicotinic acid, indicating that the sequences cloned in E. coli contained the information required to preserve the physiological responses seen in B. pertussis. Further characterization of the vir fha clones by Tn5 mutagenesis in E. coli and by the return of cloned sequences to B. pertussis in trans and to the B. pertussis chromosome led to the localization of the vir locus, the structural gene for FHA, and genes that are possibly required for the synthesis and export of FHA. PMID- 2898472 TI - Chloroplast and cytosolic glutamine synthetase are encoded by homologous nuclear genes which are differentially expressed in vivo. AB - We have shown that the individual members of the plant gene family for glutamine synthetase (GS) are differentially expressed in vivo, and each encode distinct GS polypeptides which are targeted to different subcellular compartments (chloroplast or cytosol). At the polypeptide level, chloroplast GS (GS2) and cytosolic GS (GS1 and GSn) are distinct and show an organ-specific distribution. We have characterized full length cDNA clones encoding chloroplast or cytosolic GS of pea. In vitro translation products encoded by three different GS cDNA clones, correspond to the mature GS2, GS1, and GSn polypeptides present in vivo. pGS185 encodes a precursor to the chloroplast GS2 polypeptide as shown by in vitro chloroplast uptake experiments. The pGS185 translation product is imported into the chloroplast stroma and processed to a polypeptide which corresponds in size and charge to that of mature chloroplast stromal GS2 (44 kDa). The 49 amino terminal amino acids encoded by pGS185 are designated as a chloroplast transit peptide by functionality in vitro, and amino acid homology to other transit peptides. The cytosolic forms of GS (GS1 and GSn) are encoded by highly homologous but distinct mRNAs. pGS299 encodes the cytosolic GS1 polypeptide (38 kDa), while pGS341 (Tingey, S. V., Walker, E. L., and Coruzzi, G. M. (1987) EMBO. J. 6, 1-9) encodes a cytosolic GSn polypeptide (37 kDa). The homologous nuclear genes for chloroplast and cytosolic GS show different patterns of expression in vivo. GS2 expression in leaves is modulated by light, at the level of steady state mRNA and protein, while the expression of cytosolic GS is unaffected by light. The light-induced expression of GS2 is due at least in part to a phytochrome mediated response. Nucleotide sequence analysis indicates that chloroplast and cytosolic GS have evolved from a common ancestor and suggest a molecular mechanism for chloroplast evolution. PMID- 2898473 TI - A point mutation abolishes binding of cAMP to site A in the regulatory subunit of cAMP-dependent protein kinase. AB - Each regulatory subunit of cAMP-dependent protein kinase has two tandem cAMP binding sites, A and B, at the carboxyl terminus. Based on sequence homologies with the cAMP-binding domain of the Escherichia coli catabolite gene activator protein, a model has been constructed for each cAMP-binding domain. Two of the conserved features of each cAMP-binding site are an arginine and a glutamic acid which interact with the negatively charged phosphate and with the 2'-OH on the ribose ring, respectively. In the type I regulatory subunit, this arginine in cAMP binding site A is Arg-209. Recombinant DNA techniques have been used to change this arginine to a lysine. The resulting protein binds cAMP with a high affinity and associates with the catalytic subunit to form holoenzyme. The mutant holoenzyme also is activated by cAMP. However, the mutant R-subunit binds only 1 mol of cAMP/R-monomer. Photoaffinity labeling confirmed that the mutant R-subunit has only one functional cAMP-binding site. In contrast to the native R-subunit which is labeled at Trp-260 and Tyr-371 by 8-N3cAMP, the mutant R-subunit is convalently modified at a single site, Tyr-371, which correlates with a functional cAMP-binding site B. The lack of functional cAMP-binding site A also was confirmed by activating the mutant holoenzyme with analogs of cAMP which have a high specificity for either site A or site B. 8-NH2-methyl cAMP which preferentially binds to site B was similar to cAMP in its ability to activate both mutant and wild type holoenzyme whereas N6-monobutyryl cAMP, a site A specific analog, was a very poor activator of the mutant holoenzyme. The results support the conclusions that 1) Arg-209 is essential for cAMP binding to site A and 2) cAMP binding to domain A is not essential for dissociation of the mutant holoenzyme. PMID- 2898471 TI - Pilin-gene phase variation of Moraxella bovis is caused by an inversion of the pilin genes. AB - Moraxella bovis Epp63 can express either of two different pilin proteins, called alpha and beta. We have previously cloned and sequenced the beta-pilin gene and now report that DNAs isolated from bacteria expressing alpha pilin have hybridization patterns consistently different from those of bacteria expressing beta pilin. The phase variation between alpha- and beta-pilin gene expression appears to be associated with an inversion of about 2 kilobases of DNA, whose endpoints occur within the coding region of the expressed pilin gene. Comparisons of the beta-pilin gene sequence with those of well-studied bacterial inversion systems revealed a stretch of 58% sequence similarity (21 of 36 base pairs) between the left inverted repeat of the Salmonella typhimurium flagellar hin control region and the amino-terminal portion of the beta-pilin gene. PMID- 2898474 TI - gamma-Glutamyl transpeptidase: a single copy gene in the rat and a multigene family in the human genome. AB - gamma-Glutamyl transpeptidase (GGT) genomic sequences were isolated from rat and human libraries using a rat GGT cDNA as a cross-species hybridization probe. Characterization of the human GGT clones by restriction mapping clearly establishes that at least four different GGT genes or pseudogenes are present in the human genome. All the rat genomic clones cover a 12.5-kilobase sequence and exhibit a unique restriction pattern. A precise quantitation of the rat GGT gene copy number by Southern blot analysis demonstrates that this sequence is present as a single copy/rat haploid genome. Therefore, the GGT gene organization is different between rat and human species; this raises the possibility of different regulatory mechanisms in the two species. PMID- 2898475 TI - Induction of glycogenolysis in cultured Ewing's sarcoma cells by dopamine and beta-adrenergic agonists. AB - This study describes hormonal regulation of glycogen metabolism in Ewing's sarcoma cells. 3H-Glycogen synthesized in cultured Ewing's sarcoma WE-68 cells from 3H-glucose was hydrolyzed in a concentration-dependent manner by various catecholamines. The order of potency for the glycogenolytic effects of catecholamines was isoproterenol greater than or equal to dopamine greater than norepinephrine greater than epinephrine. The concentrations giving half-maximal effectiveness (EC50) were about 2 x 10(-8) M, 3 x 10(-8) M, 8 x 10(-8) M, and 5 x 10(-7) M for isoproterenol, dopamine, norepinephrine, and epinephrine, respectively. Higher concentrations of each of the catecholamines were necessary to elicit EC50 stimulation of cyclic AMP production in Ewing's sarcoma cells. Glycogenolysis induced by dopamine was blocked by chlorpromazine, a dopamine D1 receptor antagonist, but not by haloperidol, a dopamine D2-receptor antagonist. The glycogenolytic action of norepinephrine was markedly reduced by propranolol, a beta-adrenoreceptor antagonist, and was not affected by yohimbine, an alpha adrenoreceptor antagonist. In addition, chlorpromazine also antagonized the glycogenolytic response to norepinephrine. Dibutyryl cyclic AMP, 3-isobutyl-1 methylxanthine, and the diterpene forskolin were also found to induce 3H-glycogen hydrolysis. Our data indicate that catecholamines exert their glycogenolytic effects in Ewing's sarcoma cells by stimulation of cyclic AMP formation via beta adrenergic receptors and dopamine D1-receptors. PMID- 2898476 TI - Antiproliferative effects of somatostatin and the somatostatin analog SMS 201-995 on three human breast cancer cell lines. AB - The antiproliferative effect of somatostatin and the somatostatin analog SMS 201 995 on three human breast cancer cell lines (CG5, T 47 D, and ZR 75-1) is reported. Both peptides markedly inhibited CG5 cell growth with a maximal inhibition of about 40% as compared with control cells. The antiproliferative effect of somatostatin on T 47 D and ZR 75-1 cells was much less evident. These results suggest that somatostatin is a peptide inhibitory factor for human breast cancer cells. Possible therapeutic implications of these findings are still to be investigated. PMID- 2898477 TI - Immunocytochemical localization of mutant low density lipoprotein receptors that fail to reach the Golgi complex. AB - In the low density lipoprotein (LDL) receptor system, blocks in intracellular movement of a cell surface receptor result from naturally occurring mutations. These mutations occur in patients with familial hypercholesterolemia. One class of mutant LDL receptor genes (class 2 mutations) produces a receptor that is synthesized and glycosylated in the endoplasmic reticulum (ER) but does not reach the cell surface. These receptors contain serine/threonine-linked (O-linked) carbohydrate chains with core N-acetylgalactosamine residues and asparagine linked (N-linked) carbohydrate chains of the high mannose type that are only partially trimmed. To determine the site of blockage in transport, we used electron microscope immunohistochemistry to compare the intracellular location of LDL receptors in normal human fibroblasts with their location in class 2 mutant fibroblasts. In normal cells, LDL receptors were located in coated pits, coated vesicles, endosomes, multivesicular bodies, and portions of the Golgi complex. In contrast, the mutant receptors in class 2 cells were almost entirely confined to rough ER and irregular extensions of the rough ER. Metabolic labeling studies with [3H]glucosamine confirmed that these mutant receptors contain core O-linked sugars, suggesting that the enzymes that attach these residues are located in the rough ER or the transitional zone of the ER. These studies establish that naturally occurring mutations in cell surface receptors can cause the receptors to remain trapped in the ER, thereby preventing their normal function and producing a genetic disease. PMID- 2898478 TI - Dissection of the asynchronous transport of intestinal microvillar hydrolases to the cell surface. AB - Novel subcellular fractionation procedures and pulse-chase techniques were used to study the intracellular transport of the microvillar membrane hydrolases sucrase-isomaltase and dipeptidylpeptidase IV in the differentiated colon adenocarcinoma cell line Caco-2. The overall rate of transport to the cell surface was two fold faster for dipeptidylpeptidase IV than for sucrase isomaltase, while no significant differences were observed in transport rates from the site of complex glycosylation to the brush border. The delayed arrival of sucrase-isomaltase in the compartment where complex glycosylation occurs was only in part due to exit from the endoplasmic reticulum. A major slow-down could be ascribed to maturation in and transit of this enzyme through the Golgi apparatus. These results suggest that the observed asynchronism is due to more than one rate-limiting step along the rough endoplasmic reticulum to trans-Golgi pathway. PMID- 2898480 TI - Effects of hypoxia and adrenergic stimulation induced alterations in PGI2 synthesis by diabetic coronary arteries. AB - Before the onset of histologically detectable alterations in diabetic arteries, a considerable decrease in vasodilatory potential is seen. While analyzing this phenomenon, the role of altered PGI2 synthesis in rings of coronary arteries from metabolically healthy and alloxan-diabetic dogs was measured by radioimmunoassay during baseline, under the influence of phenylephrine (100 mumol/L), and during hypoxia with or without the presence of the alpha adrenergic blocker phentolamine (5 mumol/L). Basal levels of PGI2 synthetized by healthy and diabetic coronaries were no different (7.9 +/- 2.1 and 6.4 +/- 1.4 pg/mg vessel). Phenylephrine potentiated PGI2 synthesis in controls (150 +/- 22%), while it proved to be ineffective in the diabetic animals (98 +/- 6%). Under hypoxic conditions, PGI2 production of healthy coronaries (152 +/- 24%) increased, while that in the diabetic ones (82 +/- 7%) decreased (p less than 0.01). In the presence of phentolamine no difference could be detected between the two groups. Given all these data, the decreased ability of the diabetic coronaries to vasodilate develops due to diminished PGI2 production, presumably controlled by adrenergic mechanisms. Furthermore, the more severe outcome of ischaemic heart disease in diabetes mellitus might be explained by the lack of an enhanced coronary PGI2 synthesis under hypoxic conditions. PMID- 2898479 TI - Antihistamines reverse blood-ocular barrier breakdown in experimental diabetes. AB - Retinal and other tissue histamine synthesis is increased in experimental diabetes; histamine infusion causes blood-ocular barrier breakdown in nondiabetic rats. We have examined the hypothesis that antihistamines prevent blood-ocular barrier breakdown in streptozotocin diabetes using male Sprague-Dawley rats held 28 days. During the last 7 days they were divided into these treatment groups: control (C), untreated diabetic (D), diabetic rats receiving diphenhydramine-HCl (B), diabetic rats receiving ranitidine (R) and diabetic rats receiving diphenhydramine and ranitidine (BR). Vitreous albumin content was measured 6 hr following fluorescein isothiocyanate bovine serum albumin (FITCBSA) injection. Data show that D had a 98.3% increase in vitreous body FITCBSA over C (p less than 0.05) while B and R showed respective decreases of 34.9% and 51.4% compared to D, R being significantly lower than D (p less than 0.05). BR showed a decrease of 71% (p less than 0.05) compared to D, and R and BR groups were not significantly different from C (p less than 0.05). Leakage into the vitreous was from the retina, not the ciliary body. These data indicate that 1) experimental diabetes results in elevated blood-ocular barrier permeability, which can be reversed by diphenhydramine-HCl and ranitidine; and 2) histamine H1- and H2 receptor activation and interaction by altered endogenous histamine metabolism may mediate blood-ocular barrier breakdown, implicating a pathogenic role of histamine in diabetic retinopathy. PMID- 2898481 TI - [Pancreatic fistula after left pancreatectomy. Frequency and severity]. AB - In order to study the frequency and complications related to pancreatic fistula following distal pancreatectomy we have reviewed 19 patients operated on between January 1st 1981 and February 28 1986. There was no mortality but the incidence of pancreatic fistula was 52%. 40% of these cases developed a subphrenic abscess (21% of the total number of cases). These fistulas closed after an average post operative period of 42 days. Reoperation for an infected collection was required in 4 cases. The incidence of pancreatic fistula was not related to the initial pancreatic pathology. Splenectomy did not influence the incidence of subphrenic abscess. Different techniques of closure of the distal pancreas after resection have not changed the incidence of this complication. The use of somatostatin appears to favourably influence the course of the fistula. These conclusions tend to confirm the results of other reported series. PMID- 2898483 TI - Qualitative gas chromatographic and gas chromatographic-mass spectrometric screening for beta-blockers in urine after solid-phase extraction using Extrelut 1 columns. PMID- 2898482 TI - [External supramalleolar flap in the reconstructive surgery of the foot]. AB - The external supramalleolar flap is a mixed cutaneoaponeurotic flap removed from the external surface of lower part of leg and with, as its principal vascular pedicle, the anterior perforating branch of the peroneal artery. The flap can be used in two ways: as a rotation flap with distal cutaneous hinge allowing lover third of internal surface of leg and instep to be covered, or as a retrograde flux island flap by anastomosis of perforating artery to arteries of foot. The latter procedure is of interest in that it permits covering of loss of distal substance of foot in the dorsal or plantar region. Results of use of this method in 35 patients situate the place of the external supramalleolar flap in the techniques available for lower limb repair. PMID- 2898484 TI - Specific immunoglobulin A to Bordetella pertussis antigens in mucosal secretion for rapid diagnosis of whooping cough. AB - Specific immunoglobulin A (IgA) to Bordetella pertussis filamentous hemagglutinin (FHA) and pertussis toxin (PT) was determined in mucosal secretions by an enzyme linked immunosorbent assay (ELISA). It took 3 to 4 h to complete the ELISA. The upper limits of normal values for age were determined in nasopharyngeal (NPH) secretions from 23 patients with viral infections and in 10 healthy adults working with pertussis patients or cultures. A significant IgA response to FHA was found in 38 of 54 (70%) and to PT in 28 of 54 (52%) NPH secretions from patients with pertussis confirmed by culture, serology, or both. The rate of positive responses to either antigen (44 of 54 [81%]) was significantly higher than that by culture alone (29 of 54 [54%]; P less than 0.01). The rate of positive responses increased from 65% in patients with symptoms for 1 week or less to 87 to 92% in patients with symptoms for 2 or more weeks. The specific IgA response to PT was found in 100% of NPH samples from 17 unimmunized children less than 3 years of age and in only 30% of adults and immunized children greater than 3 years of age. A response to FHA was found in 65 to 73% of the NPH secretions in all age groups. Saliva samples were found to contain specific IgA to FHA and PT in all age groups, but these were of diagnostic value in 50% (11 of 22) of the adult patients. The specificity of the ELISA was 100% (10 of 10 negatives) in NPH secretions from patients with pertussis-like cough who had negative cultures and serology. The results indicate that determination of specific IgA to PT and FHA in NPH aspirates represents a sensitive and rapid diagnostic method for the detection of pertussis. PMID- 2898485 TI - Evaluation of substrates for radiometric detection of bacteria in blood cultures. AB - Various 14C-labeled substrates were evaluated for their potential use in blood culture media. These uniformly labeled compounds were added to hypertonic and anaerobic formulations of modified Columbia broth and compared with analogous BACTEC media with the BACTEC 460. Different bacterial species gave significant growth indices when 2.0 microCi of labeled glucose, glutamic acid, aspartic acid, arginine, or formate was used alone or in combinations in the experimental media. The combination of glucose, glutamic acid, and sodium formate was selected, and simulated blood cultures with representative aerobic, facultative, and anaerobic bacteria and a yeast were compared with BACTEC vials. Under these conditions, the experimental media often became positive several hours earlier than the BACTEC vials and usually produced higher growth indices. PMID- 2898486 TI - Lytic effector cell function in schizophrenia and depression. AB - Natural killer (NK) cell activity and antibody-dependent cellular cytotoxicity (ADCC) were tested in patients with schizophrenia or depression. It was found that NK activity as well as ADCC were significantly lower in both groups, as compared to healthy control individuals (P less than 0.001). Psychopharmacologic treatment with neuroleptics and antidepressives resulted in a significant increase in NK activity and ADCC (P less than 0.005) in patients with schizophrenia but not in treated patients with depression. In patients with schizophrenia, no correlation could be established between the dose of neuroleptic given and the increase in NK activity. Lithium also did not produce an increase in NK activity and ADCC. The addition of serum, derived from untreated patients with schizophrenia, to cell cultures in concentrations of 10 and 20% had an inhibitory effect upon the ADCC and, to a lesser degree, upon NK activity (20% serum concentration only); sera from treatment schizophrenics produced no inhibition of NK activity, but did affect ADCC. No serum-derived inhibitory effect upon either NK activity or ADCC was found to be present in sera from patients with depression. We conclude that lytic effector mechanisms are impaired in patients with schizophrenia or depression and that this defect is reversed in schizophrenic patients on treatment, but not in depressives on therapy. Patients with schizophrenia also tend to have a reversible serum mediated inhibition of NK activity which is absent in patients with depression. PMID- 2898487 TI - Transient suppression of clonal hemopoiesis associated with pregnancy in a patient with a myeloproliferative disorder. AB - We have used restriction fragment length polymorphism analysis to study the clonal involvement of the blood cells in a woman with myeloproliferative disease, whose initially high platelet count (940,000/microliter) spontaneously decreased during a normal pregnancy but then returned rapidly to the same high level after delivery of her child. Analysis of her erythroid progenitors showed the presence of erythropoietin-independent progenitors before, during, and after her pregnancy, consistent with a diagnosis of myeloproliferative disease, and persistence of the abnormal clone throughout the period of study. Analysis of DNA from her blood granulocytes showed these to be polyclonal at mid-pregnancy, when her platelet count had decreased to normal values, in comparison to the monoclonal pattern exhibited by her blood granulocytes 3 mo postpartum, when her platelet count was again elevated. These results demonstrate a partial conversion to normal, polyclonal hemopoiesis during her pregnancy and suggest a previously unanticipated differential sensitivity of normal and neoplastic hemopoietic cells to physiological changes associated with this state. PMID- 2898488 TI - Rapid diagnosis of whooping cough using monoclonal antibody. AB - A counterimmunoelectrophoresis (CIE) method for antigen detection using monoclonal antibody was assessed for its ability to aid in the rapid diagnosis of Bordetella pertussis in 59 patients. A positive diagnosis from a combination of results from tests of serum and urine was obtained in 51 (87%) of cases. For sera, CIE had a sensitivity of 85% and a specificity of 94%; for urine samples the sensitivity was 81% and a specificity of 100%. Antigen detection by CIE is simple to perform and yields results on the same day, thus allowing treatment to begin at an early stage. PMID- 2898489 TI - Gamma-aminobutyric acid in the medial rat nucleus accumbens: ultrastructural localization in neurons receiving monosynaptic input from catecholaminergic afferents. AB - Neurons containing gamma-aminobutyric acid (GABA) in the medial portion of the adult rat nucleus accumbens were characterized with respect to their ultrastructure, sites of termination, and catecholaminergic input. Antisera against GABA-conjugates and the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), were localized within single sections by means of peroxidase antiperoxidase (PAP) and immunoautoradiographic labeling methods. Peroxidase reaction product indicating GABA-like immunoreactivity (GABA-LI) was seen in medium-size (15-20 microns) perikarya containing either round and unindented or invaginated nuclear membranes. The cells with invaginated nuclei were few in number and usually exhibited more intense peroxidase reaction product in sections collected at the same distance from the surface of the tissue. Reaction product for GABA was also detected in proximal (1.5-3.0 microns) dendrites, axons, and terminals. Terminals with GABA-LI formed symmetric junctions on perikarya, proximal dendrites, and dendritic spines of neurons that usually lacked detectable immunoreactivity. Many of the GABAergic terminals also were apposed directly to other unlabeled terminals and to terminals exhibiting either peroxidase labeling for GABA or immunoautoradiographic labeling for TH. Many of the unlabeled terminals associated with the GABAergic axons formed asymmetric junctions on dendritic spines. From 138 TH-labeled, principally dopaminergic terminals that were examined in the medial nucleus accumbens, 4% were associated with the somata of GABAergic neurons and another 14% formed symmetric junctions with proximal dendrite showing GABA-LI. The remaining TH-immuno-reactive terminals either lacked recognizable densities or formed symmetric synapses on unlabeled dendrites and spines. A few of the unlabeled dendrites, as well as those containing GABA-LI, received symmetric synapses from both catecholaminergic and GABAergic terminals. We conclude that in the medial portion of the rat nucleus accumbens, GABA is localized to two morphologically distinct types of neurons, one or both of which receive monosynaptic input from catecholaminergic afferents, and that GABAergic terminals form symmetric synapses on other principally non-GABAergic neurons. The results also support earlier physiological evidence showing that GABA may modulate the output of other GABAergic and non GABAergic neurons through presynaptic associations. PMID- 2898490 TI - Localization of tyrosine-hydroxylase-like-immunoreactive amacrine cells in the larval tiger salamander retina. AB - Immunocytochemistry was used to localize the populations of tyrosine-hydroxylase like (TH)-immunoreactive cells in the tiger salamander retina. Ninety percent of these cells possessed somas that were situated in the innermost cell row of the inner nuclear layer and were classified as amacrine cells. Ten percent of TH immunoreactive somas were located in the ganglion cell layer and were tentatively designated as those of displaced amacrine cells. The processes of TH immunoreactive cells ramified most heavily in sublayer 1 of the inner plexiform layer, while a relatively small number of TH-labelled processes distributed in sublayers 3 and 5. Less than 1% of TH-immunoreactive cells in the amacrine cell layer exhibited a short process of somal origin that extended distally toward the outer plexiform layer. However, these processes did not cross the whole of the inner nuclear layer, and no immunolabelling was observed in the outer plexiform layer. An examination of retinal whole-mounts revealed that TH-immunoreactive amacrine and displaced amacrine cells were distributed throughout the center and periphery of the retina. The density of TH-immunolabelled amacrine cells was calculated to be 49 +/- 13 (mean +/- standard error) cells per mm2. The vast majority of TH-immunoreactive amacrine and displaced amacrine cells exhibited a stellate appearance and gave rise to three or more primary dendrites. A few TH amacrine and displaced amacrine cells possessed two primary dendrites that emerged from opposite sides of their somas. The processes of TH-immunoreactive cells were generally poorly branched and varicose with terminal branches sometimes appearing thin and beaded. Because some TH-immunolabelled processes were very long, there was considerable overlap between the dendritic fields of neighboring TH-cells. Lastly, individual TH-immunoreactive amacrine and displaced amacrine cells were often observed in whole-mounts to provide processes that ramified at more than one level of the inner plexiform layer. PMID- 2898491 TI - A non-linear mathematical model for computerized analysis of mood curves: construction of the model and its application to the mood curves of depressive and schizophrenic inpatients. AB - A non-linear mathematical model for the computerized description of mood curves is presented. This model reaches a high goodness of fit to the real data and seems superior to a linear model recently proposed. Using this model in a computer program for describing the mood data of a large sample of psychiatric inpatients, significant and clinically meaningful group differences between the mood curves of schizophrenic, endogenous depressive, and neurotic depressive inpatients could be demonstrated. The application of this methodology might be helpful among others in the field of evaluative research. PMID- 2898493 TI - ADA and Foundation command strong presence in international dietetics. PMID- 2898492 TI - Hypochondriacal fears and beliefs in agoraphobia. AB - In order to evaluate hypochondriacal fears and beliefs in agoraphobia, the authors administered the self-rated Illness Attitude Scales to 18 agoraphobic patients. The patients reported hypochondriacal concerns similar to those of patients with hypochondriasis. After agoraphobia had been treated with exposure therapy in ten patients, hypochondriacal concerns did not differ significantly from those of normals. The findings suggest that hypochondriacal concerns are substantial in agoraphobia and that these wane when anxiety decreases. PMID- 2898494 TI - UCLA geriatric grand rounds. Hypertension in the elderly. PMID- 2898495 TI - Complementary distribution of carbamoylphosphate synthetase (ammonia) and glutamine synthetase in rat liver acinus is regulated at a pretranslational level. AB - We studied the distribution of the mRNAs for carbamoylphosphate synthetase (ammonia) and glutamine synthetase in frozen sections of adult rat liver by in situ hybridization to [35S]-labeled cDNA probes. The density of silver grains resulting from hybridization to the labeled cDNA probe for carbamoylphosphate synthetase is highest around the portal venules, decreases towards the central venule, and is virtually absent from an area two to three cells wide that lines the central venules in which mRNA for glutamine synthetase is predominantly localized. Therefore, both mRNAs show the same complementary distribution within the liver acinus that was found for the proteins they encode, demonstrating that compartmentalization of the expression of these enzymes is controlled at a pretranslational level. In addition, we found that carbamoylphosphate synthetase mRNA is present mainly in the epithelium of the crypts of the proximal part of the small intestine, whereas carbamoylphosphate synthetase protein is present in the epithelium of both crypts and villi. PMID- 2898496 TI - Lateral olivocochlear neurons contain both enkephalin and dynorphin immunoreactivities: immunocytochemical co-localization studies. AB - Antibodies to methionine enkephalin and to dynorphin B were used in an immunocytochemical study examining co-containment of enkephalins and dynorphins in olivocochlear neurons in the guinea pig lateral superior olive. Two methods of sequential co-localization were employed: one using primary antibodies from different species, the second using elution of antibodies. Co-localization of enkephalin-like and dynorphin-like immunoreactivities was found in lateral olivocochlear neurons, suggesting co-containment of enkephalins and dynorphins in this projection pathway from the lateral superior olive to the organ of Corti. PMID- 2898497 TI - Copper-H2O2 oxidation strikingly improves silver intensification of the nickel diaminobenzidine (Ni-DAB) end-product of the peroxidase reaction. AB - We propose an improved silver procedure for intensification of peroxidase staining. It utilizes the high argyrophilia of polymerized Ni-DAB as a chromogen of peroxidase histochemistry, and the capacity of Cu++-catalyzed H2O2 oxidation to suppress tissue argyrophilia without influencing the argyrophilia of the polymerized Ni-DAB. This procedure is much more effective than any previously proposed intensification technique. When used in somatostatin histochemistry, it reveals perikarya, fibers, and nerve terminals in locations at which they have never been detected in preparations where only the DAB polymer was silver intensified. PMID- 2898498 TI - Procedures and experiences with preoperative skin preparation in Sweden. AB - The current situation with preoperative skin preparation in Sweden is described. Patients are given two preoperative washes with chlorhexidine scrub, and are sent to theatre on a clean bed, so no extra linen is required. Wound infection rates are acceptably low, and use of chlorhexidine has also assisted in reduction of infection associated with central venous catheters. Use of chlorhexidine scrub is recommended to help healing of infected wounds. PMID- 2898499 TI - Preoperative whole body disinfection--a controlled clinical study. AB - Preoperative whole body washing with chlorhexidine scrub was compared with soap for its effect on prevention of wound infection in clean surgery. Two thousand and fifteen patients were studied using chlorhexidine scrub, placebo or plain soap. The overall infection rate in the control and placebo groups was 12.8% (p less than 0.05) and 11.7% as opposed to 9% (p less than 0.05) in the treated group. Three per cent fewer infections were found in treated 'clean surgery' patients, and the incidence of Staphylococcus aureus infections was reduced from 6% (bar soap) to 3% (chlorhexidine). The saving in bed occupancy from prevention of infection is a significant cost-saving. PMID- 2898500 TI - Studies on perioperative skin flora. AB - Chlorhexidine in spirit is used to reduce the skin bacterial load before surgery; and recently prewashing with chlorhexidine scrub has been advocated. We describe three studies on cardio-thoracic surgical patients--particularly those having coronary artery grafts with long leg and sternal wounds. Two studies compared prewashes with chlorhexidine scrub (Hibiscrub-ICI) or soap. Study Number One (250 patients per group) was of wound infections; and Number Two (25 patients per group) was of alterations in skin flora for 10 days postoperation. Chlorhexidine scrub failed to reduce overall wound infection rates in Study 1, although leg wounds healed more quickly with less inflammation. Study Two showed that the scrub had a significant effect on skin flora that lasted at least 3 days postoperation. Study Number Three was of 100 patients (no chlorhexidine scrub) examined for methicillin-resistant coagulase-negative staphylococci (MRSE) by cultures of swabs from the leg, sternum and chest drain site before and after operation on methicillin agar. Three per cent of patients had MRSE preoperation (1 doctor) and 23% postoperation. One thousand strains were tested by agar dilution against methicillin and chlorhexidine. MRSE had a 2-8-fold increased resistance to chlorhexidine compared to a greater than 256-fold to methicillin. Thus although chlorhexidine has a marked persistent effect on skin flora, emergence of major resistance is unlikely. Use of postoperative chlorhexidine should be investigated further. PMID- 2898501 TI - Preoperative skin preparation and surgical outcome. AB - The use of antiseptics in surgery from Lister to the present day is described. A review of current procedures for preoperative preparation for surgery is given; and some data showing that the effect of chlorhexidine on skin flora is persistent is recorded. PMID- 2898502 TI - Current thoughts on Staphylococcus epidermidis in vascular surgery. AB - Staphylococcus epidermidis (CNS) is a major cause of infection in peripheral vascular surgery. It occurs as commonly in vascular prostheses as in orthopaedic, cardiac and neurosurgical implants. Greater awareness of the possible presence of CNS in initially indolent infections, particularly in the groin, is necessary. More rapid isolation and identification techniques to separate the contaminant from the pathogenic CNS are needed. It seems that better preoperative antiseptic care of vascular patients may reduce the tendency for even 24 h cephalosporin prophylaxis to encourage the emergence of resistant CNS strains. PMID- 2898503 TI - Prevention of intraoperative wound contamination with chlorhexidine shower and scrub. AB - In a prospective, controlled, clinical trial, we found that preoperative showering and scrubbing with 4% chlorhexidine gluconate was more effective than povidone-iodine or triclocarban medicated soap in reducing skin colonization at the site of surgical incision. Mean log colony counts of the incision site were one half to one log lower for patients who showered with chlorhexidine compared to those who showered with the other regimens. No growth was observed on 43% of the post shower skin cultures from patients in the chlorhexidine group compared with 16% of the cultures from patients who had povidone-iodine showers and 5% of those from patients who used medicated soap and water. The frequency of positive intraoperative wound cultures was 4% with chlorhexidine, 9% with povidone-iodine and 14% with medicated soap and water. This study demonstrates that chlorhexidine gluconate is a more effective skin disinfectant than either povidone-iodine or triclocarban soap and water and that its use is associated with lower rates of intraoperative wound contamination. PMID- 2898504 TI - The Ig kappa L chain allelic groups among the Ig kappa haplotypes and Ig kappa crossover populations suggest a gene order. AB - The Ig kappa complex locus of inbred mice found on chromosome 6 contains one constant (C kappa), five joining (J kappa), and 100 to 300 variable (V kappa) exons and spans an estimated 500 to 2000 kbp of DNA. The V kappa exons are organized into groups of highly homologous coding regions (approximately 300 bp) separated by approximately 10 kbp of intervening sequence. A group contains from 1 to 30 or more exons (exon refers to uninterrupted coding region DNA which is capable of encoding all or part of V kappa gene) that can be detected with specific DNA probes in conjunction with restriction endonuclease fragments (REF) from genomic DNA. Thirteen DNA probes specific for different V kappa exon groups and one DNA probe specific for J kappa and C kappa exons were used in conjunction with 55 inbred strains in an attempt to detect RFLP that could be used to establish Ig kappa allelic groups and Ig kappa haplotypes. Each probe detected two to four different REF patterns (allelic groups) among the panel of inbred mice examined. Size estimates of the REF were made, and each probe detected 4.2 to 107.7 kbp of DNA, including faint REF, 675.6 to 723.6 kbp of DNA could be detected within a single haplotype. Based on these allelic groups, seven haplotypes were identified among the 55 inbred strains of mice. No subline differences were detected, and the distribution of allelic groups implied common ancestry among many of the inbred strains examined. The DNA probes were also used in conjunction with recombinant inbred, congenic strains and backcross populations of mice. By using the analysis of known Ig kappa r populations, and assuming a common ancestry among the inbred strains, a gene order was predicted: Centromere-Hd-(Ig kappa-V11, Ig kappa-V24, Ig kappa-V9-26)-(Ig kappa-V1, Ig kappa V9)-(Ig kappa-V4, Ig kappa-V8, Ig kappa-V10, Ig kappa-V12, 13, Ig kappa-V19)-(Ig kappa-V28, Rn7s-6)-Ig kappa-V23-(Ig kappa-V21, Ig kappa-J, Ig kappa-C)-(Ly2, Ly3) wa-1. PMID- 2898505 TI - Slot-machine mutagenesis of a polymorphic residue on the A kappa alpha-chain. AB - This study explores the limitations on variability at a polymorphic position of an MHC class II molecule. Using a convenient and rapid method termed "slot machine mutagenesis," we have converted Glu75 on the A kappa-chain to 15 alternative amino acids. This residue is of interest because it is an immunodominant site on the A kappa alpha chain and because it participates in certain T cell epitopes. The wild-type and mutant A kappa alpha cDNA were transfected into L cells (together with the A kappa beta cDNA and a selection marker), and transfectants displaying high surface levels of the A kappa complex were selected and expanded. We sought to examine three questions: what is the effect of these mutations on the expression and overall conformation of the A alpha: A beta complex? How do these diverse mutations influence mAb epitopes for which Glu75 makes a direct contribution to specificity? Do such substitutions affect T cell recognition of the A kappa alpha:A kappa beta complex? The answers to these three questions are quite different. Position 75 of the A alpha chain can accommodate essentially all chemically divergent amino acids without major consequences for expression and overall A alpha:A beta structure. In contrast, mAb that recognize Glu75-dependent epitopes are extremely particular about the amino acid residing at this position. T cells are less fastidious: those that are affected by the mutations still recognize a number of substitutions. These data emphasize the tolerance of MHC molecules to evolutionary tampering. PMID- 2898506 TI - Phenotypic heterogeneity and cytotoxic activity of Con A and IL-2-stimulated cultures of mouse Thy-1+ epidermal cells. AB - Short-term and long-term cultures of mouse Thy-1+ epidermal cells (EC) were established in order to characterize their phenotypic and functional properties. Concanavalin A (Con A) and Interleukin 2 (IL-2) stimulated Thy-1+ EC mediated non MHC directed cytotoxicity preferentially against the NK-sensitive target, YAC-1 vs the NK-resistant target, P815; these cells also mediated antibody-dependent cell-mediated cytotoxicity (ADCC), indicating the presence of IgG-FcR on at least some of them. Freshly isolated Thy-1+ EC failed to lyse YAC-1 targets; however, this activity was observed after 9 d of culture with Con A and IL-2. While dendritic Thy-1+ EC, in vivo, do not express the T-cell markers, L3T4 and Lyt-2, short-term cultured cells displayed phenotypic heterogeneity with small but significant percentages of Lyt-2+ and L3T4+ cells appearing transiently. The phenotype of the effector cell(s), which mediates cytotoxic activity, was determined by utilizing flow cytometry to sort short-term cultured EC into positively and negatively stained populations. Cells which express L3T4, or which lack asialo GM1, did not lyse YAC-1 targets; maximum cytotoxic activity was found within populations of cells which are asialo GM1+, Lyt-2-, and asialo GM1+, Lyt 2+. These studies indicate that Thy-1+ cells derived from mouse epidermis when cultured in the presence of Con A and IL-2 have the capacity to generate a phenotypically heterogeneous population, some cells of which are capable of mediating cytotoxic activities. PMID- 2898508 TI - Downregulation of cell adhesion molecules LFA-3 and ICAM-1 in Epstein-Barr virus positive Burkitt's lymphoma underlies tumor cell escape from virus-specific T cell surveillance. AB - Some EBV+ BL cell lines continue to grow as single cells on in vitro passage, show an unusually restricted expression of EBV-latent genes and retain a BL biopsy-like cell surface phenotype (group I/II lines); others change to growth in aggregates, show a broader pattern of virus latent gene expression, and develop a cell surface phenotype more characteristic of EBV-transformed LCL (group III lines). Here we show that the cell surface adhesion molecules LFA-1, ICAM-1, and LFA-3 are expressed at very low levels, if at all, on group I/II lines and are coordinately upregulated as BL lines move towards group III. The change to growth in aggregates reflects the increasing availability of LFA-1 and ICAM-1, the two ligands whose mutual interaction underlies homotypic BL cell adhesion in vitro. The low levels of ICAM-1 and LFA-3 on group I/II BL cell lines are also associated with an impaired ability to interact with EBV-specific CTL in the antigen-independent phase of effector/target conjugation. mAb blocking studies show that the small number of conjugates that are formed with group I/II BL targets involve the LFA-1/ICAM-1 adhesion pathway but not the LFA-3 pathway; in contrast, both pathways contribute to the efficient conjugate formation shown by group III BL or LCL targets. Earlier work identified one group III line, WW1 BL, as unusual since is expressed the full spectrum of EBV-latent proteins yet remained insensitive to lysis by EBV-specific CTL. Here we show that this line has an anomalous pattern of adhesion molecule expression with high levels of LFA 1 and ICAM-1 in the absence of detectable LFA-3. The WW1 BL cells form conjugates with EBV-specific CTL through the LFA-1/ICAM-1 pathway, but in the absence of a target LFA-3/effector CD2 interaction these conjugates do not achieve target cell lysis. This may reflect an important role for target LFA-3 molecules in activating EBV-specific CTL function. From these in vitro studies, we postulate that downregulation of the adhesion molecules LFA-3 and ICAM-1 on EBV+ BL underlies the ability of the malignant clone to evade EBV-specific T cell surveillance in vivo. PMID- 2898507 TI - The Ebner glands: a pancreatic-like gland secreting an acid lipase. Secretory regulation in vitro. AB - The lingual serous glands of rat tongue, the Ebner glands, secrete a potent acid lipase that acts in the stomach where it initiates the digestion of dietary fat. The factors affecting its secretion were studied 'in vitro' on Ebner slices. The lipolytic activity was measured in the incubation medium using tributyrine as substrate and by titration at pH: 5.4. Cholecystokinin (10(-9) M) and carbachol (10(-5) M) efficiently stimulated lipase secretion (3 fold over basal rate). The parasympathetic agent triggered secretion involving a calcium dependent system. Atropin (10(-4) M) blocked this cholinergic effect by about 40%. Lipase secretion was stimulated by epinephrine and isoproterenol. Propranolol (beta-antagonist) inhibited the adrenergic stimulation, while phentolamine was ineffective. The inhibitory effect of the selective beta 1-antagonist (Betaxolol) and the lack of effect of the selective beta 2-antagonist (ICI 118551) suggest the participation of beta 1-adrenoceptors in the secretion mechanism. PMID- 2898509 TI - Reactive arthritis following a sting by a Portuguese man-of-war. PMID- 2898510 TI - Astrocytic responses to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) in cat and mouse brain. AB - Glial fibrillary acidic protein immunohistochemistry was used as a selective marker for regional reactive gliosis in the striatum and ventral mesencephalon in cats and mice exposed to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. Thirty mice (C-57 black strain) were injected with 30 mg/kg intraperitoneally (IP) MPTP.HCl for seven days. Five adult cats were injected with 10 mg/kg IP MPTP.HCl for seven days. Animals were killed five to seven days after the last MPTP injection. Reactive gliosis was observed throughout the mouse striatum but not in the substantia nigra. In contrast, reactive gliosis was topographically represented in the cat caudate nucleus with a dorsal-ventral and medial-lateral gradient evident. Gliosis was also observed in the putamen and the substantia nigra, pars compacta. Tyrosine hydroxylase immunocytochemistry revealed a loss of dopamine in the mouse striatum but no loss of substantia nigra neurons. Nigral neurons were destroyed in the cat. These results suggest that MPTP may destroy nigrostriatal dopamine cell bodies and terminals in the cat while destruction in the mouse is at least initially confined to striatal terminals. PMID- 2898511 TI - Synaptic and intrinsic responses of medical entorhinal cortical cells in normal and magnesium-free medium in vitro. AB - 1. Extracellular recordings were made from slices of hippocampus plus parahippocampal regions maintained in vitro. Field potentials, recorded in the entorhinal cortex after stimulation in the subiculum, resembled those observed in vivo. 2. Washout of magnesium from the slices resulted in paroxysmal events which resembled those occurring during sustained seizures in vivo. These events were greatest in amplitude and duration in layers IV/V of the medial entorhinal cortex and could occur both spontaneously and in response to subicular stimulation. Spontaneous seizure-like events were not prevented by severing the connections between the hippocampus and entorhinal cortex, but much smaller and shorter events occurring in the dentate gyrus were stopped by this manipulation. Both spontaneous and evoked paroxysmal events were blocked by perfusion with the N methyl-D-aspartate (NMDA) receptor antagonist, DL-2-amino-5-phosphonovalerate (2 AP5). 3. Neurons in layers IV/V were characterized by intracellular recording. Injection of depolarizing current in most cells evoked a train of nondecrementing action potentials with only weak spike frequency accommodation and little or no posttrain after hyperpolarization. 4. A small number of cells displayed burst response when depolarized by positive current. The burst consisted of a slow depolarization with superimposed action potentials which decreased in amplitude and increased in duration during the discharge. The burst was terminated by a strong after hyperpolarization and thereafter, during prolonged current pulses a train of nondecrementing spikes occurred. The burst response remained if the cell was held at hyperpolarized levels but was inactivated by holding the cell at a depolarized level. 5. Depolarizing synaptic potentials could be evoked by stimulation in the subiculum. A delayed and prolonged depolarization clearly decremented with membrane hyperpolarization and, occasionally, increased with depolarization. 6. Washout of magnesium from the slices resulted in an enhancement of the late depolarization and a reversal of its voltage dependence. Eventually a single shock to the subiculum evoked a large all-or-none paroxysmal depolarization associated with a massive increase in membrane conductance. Similar events occurred spontaneously in all cells tested. The paroxysmal depolarizations, both spontaneous and evoked, were rapidly blocked by 2-AP5. 7. It is concluded that medial entorhinal cortical cells possess several intrinsic and synaptic properties which confer an extreme susceptibility to generation of sustained seizure activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2898512 TI - Seizures induce dramatic and distinctly different changes in enkephalin, dynorphin, and CCK immunoreactivities in mouse hippocampal mossy fibers. AB - Light microscopic immunocytochemical techniques were used to evaluate the influence of recurrent limbic seizure activity on the immunoreactivity for 3 neuropeptides--enkephalin, dynorphin, and cholecystokinin (CCK)--contained within the mouse hippocampal mossy fiber axonal system. Seizures were induced either by the placement of a small unilateral electrolytic lesion in the dentate gyrus hilus or by intraventricular injection of kainic acid. Both treatments induce epileptiform activity in hippocampus lasting several hours. Four days after either lesion placement or injection of 0.05-0.1 microgram kainic acid, immunoreactivity for all 3 peptides was altered throughout the intact mossy fiber system, bilaterally, but in distinctly different ways: enkephalin immunoreactivity (ENK-I) was dramatically elevated, dynorphin immunoreactivity was reduced, and CCK immunoreactivity (CCK-I) was either severely reduced or completely absent in the mossy fiber system. ENK-I was also clearly increased in other areas, including the lateral septum, the entorhinal cortex, and within the entorhinal (perforant path) efferents to temporal hippocampus. In contrast, the loss of CCK seemed restricted to the mossy fiber system in that immunostaining appeared normal in scattered hippocampal perikarya, within the dentate gyrus commissural system, as well as within other limbic structures. Four days after injections of 0.2 or 0.25 microgram kainic acid, mossy fiber ENK-I was greatly elevated, dynorphin immunoreactivity was reduced, but, unlike the situation with lower kainic acid doses, CCK-I was only modestly reduced in the mossy fibers and was clearly reduced in other hippocampal systems as well. These data indicate that epileptiform physiological activity differentially affects the regulation of 3 neuroactive peptides contained within the hippocampal mossy fiber system and suggest a mechanism through which seizurelike episodes can have a lasting influence on the operation of specific hippocampal circuitries. PMID- 2898514 TI - Locomotion produced in mesencephalic cats by injections of putative transmitter substances and antagonists into the medial reticular formation and the pontomedullary locomotor strip. AB - The purpose of this study was to determine the distribution of cells in the medial reticular formation (MRF) and the pontomedullary locomotor strip (PLS), which can induce locomotion when activated. Controlled microinjections of neuroactive substances (Goodchild et al., 1982) into the MRF or PLS were made in order to activate cell bodies in those areas. The ability of trigeminal receptive field stimulation to induce locomotion before and after drug infusion into the PLS was also assessed since the PLS and the spinal nucleus of the trigeminal nerve are similar in their anatomical distribution. Experiments were performed on precollicular-postmamillary decerebrate cats walking on a treadmill. Injections of glutamic acid (GA; 500 nmol) into the MRF produced locomotion that was antagonized by infusion of glutamic acid diethyl ester into the same spot. Decreases in the current threshold for locomotion produced by electrical stimulation of the MRF were observed when the MRF was infused with either GA (40 80 nmol), DL-homocysteic acid (DL-HCA; 200 nmol), or picrotoxin (PIC; 15 nmol). Injections of GA (100 nmol), DL-HCA (700 nmol), PIC (10-50 nmol), and substance P (2 nmol) into the PLS also produced locomotion. Locomotion produced by injections of PIC into the PLS was blocked by infusion of equal amounts of muscimol or GABA. Effective PLS injection sites were all confined to the trigeminal spinal nucleus or immediately ventral and medial to this in the adjacent lateral reticular formation. Trigeminal nerve peripheral field stimulation evoked locomotion after microinjection of PIC into the PLS, although this same facial stimulus was not effective prior to drug injection. We conclude that the MRF and PLS regions of the cat brain stem contain cells that produce locomotion when chemically stimulated, and we suggest that the PLS is closely related to or synonymous with the spinal nucleus of the trigeminal nerve. Furthermore, we suggest that stimulation of trigeminal afferents is analogous to stimulation of segmental afferent pathways in the production of locomotion (Sherrington, 1910; Jankowska et al., 1967; Afelt, 1970; Budakova, 1972; Grillner and Zangger, 1979). PMID- 2898513 TI - Comparison of primary afferent and glutamate excitation of neurons in the mammalian spinal dorsal horn. AB - The actions of L-glutamate and agonists, agents blocking their membrane receptors and dorsal root afferent volleys, were compared on intracellularly recorded neuronal activity in an in vitro horizontal slice preparation of the hamster spinal dorsal horn. Bath-applied L-glutamate or L-aspartate (less than or equal to 1 mM) rapidly depolarized and excited less than a third of the dorsal horn neurons sampled. Bathing solutions containing low Ca2+ eliminated synaptic transmission in the slices but failed to block the excitatory effects of L glutamate for the majority of the neurons tested. N-Acetylaspartylglutamate had no effect on dorsal horn neurons at concentrations up to 1 mM. Neurons excited by L-glutamate were most commonly located in the superficial dorsal horn (laminae I and II). Neurons insensitive to L-glutamate were more broadly distributed, with a number being located in laminae III-V. Kynurenic acid, 2-amino-4-phosphonobutyric acid, and 2,3-piperidine dicarboxylic acid selectively antagonized rapid, short lasting synaptic components of the dorsal cord potentials. Kynurenic acid reversibly antagonized intracellularly recorded L-glutamate-induced excitation, spontaneous synaptic potentials, and fast synaptic potentials evoked by dorsal root volleys. Compounds with strong antagonist actions at the NMDA receptor, 2 amino-5-phosphonovaleric acid and D-alpha-aminoadipic acid, were much less effective in suppressing the effects of L-glutamate or in blocking synaptic potentials. We conclude that a subset of spinal neurons directly excited by dorsal root fibers have excitatory membrane receptors activated by L-glutamate. This conclusion is consistent with the concept that L-glutamate or a substance binding to the receptors it activates is released from the central terminals of some primary afferent fibers and mediates fast synaptic transmission from them to certain spinal neurons in the dorsal horn. PMID- 2898516 TI - Characterization and regional distribution of glutamatergic and cholinergic ligand binding sites in goldfish brain. AB - The binding of several ligands that selectively interact with glutamate receptor subtypes was characterized in extensively washed synaptosomal membrane preparations from goldfish brain. The binding affinity (Kd), an estimate of the number of sites (Bmax), the rank-order potency of glutamatergic ligands at inhibiting binding, and the regional localization of binding sites were determined. In whole brain preparations, 3H-kainate had a Kd of 136 nM and a Bmax of 63 pmol/mg protein, 3H-AMPA had a Kd of 26 nM and a Bmax of 0.4 pmol/mg protein, and 3H-L-glutamate bound with an apparent affinity of 323 nM and a Bmax of 5 pmol/mg protein. Most of the binding sites for each of the glutamate analogs were present in the cortex and the fewest were in the cerebellum, except for 3H kainate binding sites, which were most prevalent in the cerebellum and least abundant in the cortex. The proposed neuronal nicotinic acetylcholine receptor (nAChR) ligands 3H-(-)nicotine and 125I-alpha-Bgt were also investigated. 125I alpha-Bgt had a Kd of 0.08 nM and a Bmax of 132 fmol/mg protein. 3H-(-)nicotine did not bind to the extensively washed membrane preparations, so a less stringently washed P2 tissue fraction was used. In this tissue preparation, 3H-( )nicotine had a Kd of 9 nM and a Bmax of 84 fmol/mg protein. Eye removal resulted in a time-dependent decrease in the number of 3H-(-)nicotine and 125I-alpha-Bgt binding sites in the contralateral optic tectum, but no reduction in the number of binding sites for any of the glutamatergic ligands. The results suggest that both 3H-(-)nicotine and 125I-alpha-Bgt binding sites are similarly regulated in the optic tectum, which supports previously reported data indicating that the binding sites are located on closely related proteins or may, at least partially, be colocalized on the same protein (Henley and Oswald, 1987).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898515 TI - Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons. AB - The present study examined the effects of glutamate on the outgrowth of dendrites and axons in isolated hippocampal pyramidal-like neurons in cell culture. During the first day of culture the survival and outgrowth of these neurons was unaffected by high concentrations (up to 1 nM) of glutamate, quisqualic acid (QA), kainic acid (KA), and N-methyl-D-aspartic acid. Beginning on day 2 of culture high levels of glutamate, KA and QA were toxic to the majority of pyramidal neurons, while subtoxic levels of these agents caused a well-defined, dose-dependent, sequence of effects on dendritic outgrowth. At increasing concentrations of glutamate, QA, and KA, the following events were observed: (1) dendritic outgrowth rates were reduced, while axonal elongation rates were unaffected; (2) dendritic length was reduced, while axons continued to grow; (3) dendrites regressed dramatically, and axonal outgrowth rate was reduced. These dendrite-specific effects of glutamate were apparently mediated at the growth cones since focal application of glutamate to individual dendritic growth cones resulted in suppression of growth cone activity and a regression of the dendrite; axons were unaffected by focal glutamate application. Pharmacological tests using glutamate receptor agonists and antagonists demonstrated that receptors of the KA/QA type mediated the glutamate effects on outgrowth and survival. The calcium channel blocker Co2+ prevented both glutamate neurotoxicity and glutamate-induced dendritic regression. Ionophore A23187 and elevations in extracellular K+ levels each caused a dose-dependent series of outgrowth and survival responses similar to those caused by glutamate. Taken together, these results indicate that activation of glutamate receptors leads to the opening of voltage-dependent calcium channels; the resulting increases in calcium influx lead to the observed alterations in dendritic outgrowth and neuronal survival. PMID- 2898517 TI - Glutamate-like immunoreactivity in identified neuronal populations of insect nervous systems. AB - Glutamate is considered to be the most likely transmitter candidate at excitatory synapses onto skeletal muscles of insects. We investigated the distribution of glutamate-like immunoreactivity (Glu-LI) in identified motor neurons of glutaraldehyde-fixed metathoracic ganglia of the locust in paraffin serial sections. The presumably glutamatergic fast and slow extensor tibiae motor neurons show Glu-LI, whereas other cells, including the GABAergic common inhibitory motor neurons and the cluster of octopaminergic dorsal unpaired median cells, show rather low levels of staining. Immunoreactivity of the fast extensor tibiae motor neuron is located in soma, neurites, axon, and the terminal arborizations. A double-labeling experiment on sections of the locust metathoracic ganglion showed that antisera against glutamate and GABA discriminate between the presumably glutamatergic and GABAergic motor neurons and that GABA-LI-positive neurons are low in Glu-LI. The results suggest that Glu-LI can be used as a marker for detecting potential glutamatergic neurons in insects under the present conditions. Application of the glutamate antiserum to sections of the honeybee brain revealed Glu-LI in motor neurons but also in certain interneurons. The most prominent populations of Glu-LI-positive cells were the monopolar cells and large ocellar interneurons, which are first-order interneurons of the visual and ocellar system. Several groups of descending interneurons also showed Glu-LI. The distributions of Glu-LI and GABA-LI are complementary in locust and bee ganglia. The high level of Glu-LI in certain interneuronal populations, as well as in identified glutamatergic motor neurons, suggests that insect central nervous systems may contain glutamatergic neuronal pathways. PMID- 2898518 TI - Therapeutic basis in cryptorchidism. A clinical and experimental study. PMID- 2898520 TI - Surgical repair of the foot with muscle transposition. A case report. PMID- 2898519 TI - Crohn's disease of the esophagus: a case report and review of the literature. AB - Esophageal involvement with Crohn's disease has been rarely reported and pathologic documentation of granulomatous disease is often missing. A 12-year-old boy who presented initially with dysphagia, odynophagia, and weight loss was found to have granulomatous esophagitis, gastritis, and subsequent colitis by endoscopic examination. Esophageal manometry showed a hypertensive lower esophageal sphincter with normal peristalsis and sphincter relaxation. The esophageal symptoms responded to oral steroids and sulfasalazine without any specific treatment for acid peptic disease. This case is the youngest reported patient with Crohn's disease of the esophagus. A review of the medical literature illustrates salient clinical, radiographic, endoscopic, and pathologic features of esophageal involvement in Crohn's disease. This case and the summarized cases emphasize the potential significance of esophageal symptoms in patients with Crohn's disease. PMID- 2898521 TI - Local actions of trimebutine maleate in canine small intestine. AB - A study of the local actions of trimebutine (TMB) maleate and its N-diesmethyl metabolite (TMB-M) was carried out in the gastrointestinal tract of anesthetized dogs. In the unstimulated small intestine, but not in the stomach or colon, i.a. TMB and TMB-M caused activation of circular muscle. Like the activation by i.a. [Met5]-enkephalin, this was antagonized by naloxone. In field-stimulated segments of stomach and small intestine circular muscle, TMB or TMB-M, like dynorphin-1-13 or [Met5]-enkephalin, inhibited the phasic and tonic contractions which were mediated mostly by cholinergic, postganglionic nerves. However, the inhibitory effects of dynorphin-1-13 or [Met5]-enkephalin on small intestine were antagonized by naloxone whereas those of TMB sometimes or those of TMB-M usually were not. TMB or TMB-M did not affect responses to i.a. acetylcholine, but high doses reduced the contractile responses to subsequent field stimulation and excitatory responses to [Met5]-enkephalin. We concluded that the excitatory local actions of TMB or TMB-M on small intestine involved opioid receptors probably of the mu or delta types. Inhibitory local actions on nerve-mediated responses, however, may not have involved opioid receptors. Comparison of these data to results when TMB or TMB-M were given i.v. suggests that these agents also have peripheral actions to affect gastrointestinal motility at sites outside the gastrointestinal tract. PMID- 2898522 TI - Vasopressin inhibits sympathetic ganglionic transmission but potentiates sympathetic neuroeffector responses in hindlimb vasculature of rabbits. AB - To determine whether vasopressin (AVP) affects vasoconstrictor responses to electrical stimulation of sympathetic nerves or i.a. norepinephrine (NE), changes in perfusion pressure were measured during lumbar sympathetic nerve stimulation (LSNS, 1-8 Hz), or administration of NE (50-200 ng), in the isolated constant flow perfused hind limb of chloralose-anesthetized rabbits (n = 7), before and after i.a. infusion of AVP (0.65 mU/kg/min). AVP significantly potentiated responses to LSNS (relative potency (RP) = 1.59) and to NE (RP = 5.17). The potentiation of LSNS and NE by AVP infusion was abolished by the AVP V1 antagonist, d(CH2)5[Tyr(Me)2]AVP, 400 ng, total dose (n = 6). Because there was a significant difference between the RP of LSNS (stimulation of both preganglionic and postganglionic nerves) and NE (direct effect on the vascular smooth muscle), we verified whether this difference might represent disparate actions of AVP on the ganglia and/or sympathetic neuroeffector sites. To evaluate responses to stimulating only the postganglionic sympathetic nerves, we repeated the above study in animals pretreated with a supramaximal dose of the ganglionic blocking agent hexamethonium (25 mg/kg i.v.). After ganglionic blockade the responses to LSNS were reduced to 22% of control. In the presence of ganglionic blockade, AVP potentiated responses to LSNS (RP = 4.09) (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898523 TI - Elevation of serum prolactin and corticosterone concentrations in the rat after the administration of 3,4-methylenedioxymethamphetamine. AB - The racemic mixture of 3,4-methylenedioxymethamphetamine (MDMA), which has been reported to produce selective destruction of serotonergic neurons in the central nervous system, was studied to determine its neuroendocrine and temperature effects and mechanism of action. MDMA elevated serum concentrations of corticosterone in doses ranging from 3 to 20 mg/kg administered i.p. Serum corticosterone concentrations were elevated 30 min after the administration of MDMA (10 mg/kg i.p.) and remained elevated 4 hr later. Serum prolactin (PRL) concentrations were elevated by administration of MDMA in doses ranging from 1 to 20 mg/kg i.p., and were maximal 60 min after the injection of 10 mg/kg i.p., declining rapidly over the next 4 hr. MDMA also significantly elevated the body temperature of rats maintained at ambient (23 degrees C) temperature. MDMA induced corticosterone secretion and hyperthermia were blocked by the 5 hydroxytryptamine (5-HT) antagonists, ketanserin and mianserin, which have a high affinity for 5-HT2 binding sites. Conversely, neither (-)-pindolol, a beta antagonist that also blocks 5-HT1A-mediated responses, nor the nonspecific 5-HT antagonists, cyproheptadine and metergoline, had an effect on MDMA-induced corticosterone secretion. None of the 5-HT antagonists blocked MDMA-induced PRL secretion. Pretreatment with fluoxetine (10 mg/kg i.p.) 16 hr before MDMA administration significantly blunted the effect of MDMA on corticosterone but not PRL secretion. Pretreatment with p-chlorophenylalanine (150 mg/kg i.p.) for 3 days depleted cortical and hypothalamic 5-HT and 5-hydroxyindoleacetic acid by approximately 80% and significantly attenuated MDMA-induced corticosterone and PRL secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898524 TI - Effects of an alpha-2 adrenoceptor agonist on angiotensin converting enzyme inhibitor-induced hypotension and potentiated allergen-evoked inflammatory skin responses. AB - Angiotensin converting enzyme (ACE) inhibitors have been demonstrated to possess proinflammatory properties. Persistent cough and increased broncho-obstruction have been reported frequently in hypertensive subjects on ACE inhibitor therapy. We have studied the effect of an alpha-2 adrenoceptor agonist, clonidine, on MK 422 (active parent diacid of enalapril)-induced hypotension and potentiated inflammatory skin responses in ovalbumin-sensitized guinea pigs. Clonidine was found to abolish dose-dependently MK 422-potentiated ovalbumin-evoked inflammatory dermal responses and it possesses additive hypotensive effects when combined with the ACE inhibitor. It would therefore be interesting to evaluate further alpha-2 adrenoceptor agonists and ACE inhibitors in a combination therapy in humans when single drug antihypertensive therapy of the drugs is insufficient. PMID- 2898525 TI - Beta adrenoceptors in the canine large coronary arteries: beta-1 adrenoceptors predominate in vasodilation. AB - Beta adrenoceptors of the canine large coronary artery were characterized by observing the effects of the subtype selective antagonists, metoprolol (beta-1) and ICI 118,551 (beta-2), on the vasodilator responses of isolated and perfused preparations to beta adrenoceptor agonists and in the radioligand binding assay. The integrity of the endothelium was checked by acetylcholine-induced vasodilations. Without any precontraction, isoproterenol, norepinephrine, epinephrine and procaterol (selective beta-2 agonist) dilated the canine large coronary artery pretreated with phentolamine (10(-5) M). The rank order of agonist potency was isoproterenol greater than norepinephrine greater than epinephrine greater than procaterol. The pA2 values for metoprolol and ICI 118,551 were determined by the antagonisms of the vasodilator responses to isoproterenol and procaterol. The slopes of Schild plots for metoprolol and ICI 118,551 against isoproterenol and the value for ICI 118,551 against procaterol were not significantly different from unity, but the value for metoprolol against procaterol was significantly less than unity. The pA2 value for metoprolol against isoproterenol was 7.48 and those values for ICI 118,551 against isoproterenol and procaterol was 7.19 and 7.25, respectively. These pA2 values are typical for beta-1 adrenoceptors. The beta adrenoceptors of the canine large coronary artery were examined further using an antagonist [125I]iodocyanopindolol as a ligand for the binding of beta adrenoceptors. The [125I]iodocyanopindolol binding to the canine coronary artery smooth muscle membrane was saturable with a KD of 63.7 pM and a total number of radioligand binding sites of 44 fmol/mg of protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898526 TI - Cholinergic transmission in the superior cervical ganglion reinnervated by peripheral vagal stump cut below the nodose ganglion in cats. AB - In cats, the peripheral stump of the vagus nerve cut below the nodose ganglion was sutured with preganglionically denervated superior cervical ganglion (SCG). Cross-anastomosis were performed in a total of 23 cats, of which 21 survived. In 20 cats, after 9 to 13 weeks of surgery, functional reinnervation of SCG by the vagus was established by contraction of the nictitating membrane in response to stimulation of the vagal preganglionic trunk. This contraction was reduced by the treatment with hexamethonium and atropine. Stimulation of the vagal preganglionic trunk caused release of acetylcholine into perfusate through the anastomosed SCG perfused with Kreb's solution. It is concluded that the vagal afferent fibers do reinnervate the preganglionically denervated SCG and the pharmacological nature of this reinnervated SCG is, at least in part, cholinergic. PMID- 2898528 TI - The post-receptor era or the receptor and beyond. PMID- 2898527 TI - [D-Pro10]-dynorphin(1-11) is a kappa-selective opioid analgesic in mice. AB - The synthetic opioid agonist [D-Pro10]-dynorphin(1-11) (DPDYN) binds kappa receptors with both high affinity and selectivity in vitro. We have examined the in vivo characteristics (i.e., analgesic properties) of the peptide in mice. The analgesic effects of i.c.v. administered DPDYN were determined in two nociceptive tests, involving thermal cutaneous (tail-flick) and chemical visceral (AcOH induced writhing) stimuli, in which mu and kappa receptors are known to be activated differentially. The antinociceptive action of DPDYN was compared with that of 1) morphine and U-50,488H, which are, respectively, the prototypical mu and kappa agonists, 2) dynorphin A which is the endogenous parent peptide and 3) Leu-enkephalin, which represents the N-terminal sequence of DPDYN. DPDYN did not show any activity against thermal stimulus but, in contrast, produced a dose related effect against chemical pain. In the AcOH-writhing test, there was no significant cross-tolerance between morphine and DPDYN in mice made tolerant to morphine. Pretreatment with low doses of s.c. naloxone (less than 1 mg/kg) antagonized completely the antinociceptive action of morphine but only partially reversed the analgesic action of DPDYN. In gastrointestinal studies, DPDYN as well as U-50,488H were ineffective (maximum effect lower than 25%) in inhibiting intestinal transit in mice, in contrast to morphine which produced a dose-related antitransit effect reaching 100%. These data indicate that the in vivo properties, and particularly analgesia, of i.c.v. administered DPDYN are mediated by a "non-mu" (presumably kappa) opioid receptor at the supraspinal level of the opioid system of the mouse. PMID- 2898529 TI - Differentiation of alpha-adrenergic receptors using pharmacological evaluation and molecular modeling of selective adrenergic agents. AB - Subtypes of alpha adrenergic receptors were studied using selective adrenergic agonists. A-53693, A-54741, and related compounds were evaluated for their affinity for alpha receptor subtypes using radioligand binding techniques. Efficacy and potency were also evaluated using in vitro bioassays of alpha-1 receptors in rabbit aorta smooth muscle and alpha-2 receptors in the phenoxybenzamine-pretreated canine saphenous vein. Active and inactive compounds were then submitted for computer-assisted molecular modeling evaluation to ascertain the structural requirements for optimal potency and selectivity. Rigid catecholamines such as A-53693 display a high degree of selectivity for alpha-2 compared to alpha-1 receptors, probably because of the unique regions of space at the ligand binding site occupied by active compounds. Imidazolines such as A 54741 also interact with extremely high affinity and potency for alpha-2 receptors, and to a lesser extent at alpha-1 receptors. The spatial domains occupied by phenethylamines and imidazolines differ, each having unique regions of permissable space at alpha receptors. Compounds such as A-53693 and A-54741 are extremely useful probes of the molecular interactions of alpha agonistic compounds which will help in the design of even more selective drugs for alpha adrenergic receptors. PMID- 2898530 TI - Modulation of ANP receptor-mediated cGMP accumulation by atrial natriuretic peptides and vasopressin in A10 vascular smooth muscle cells. AB - ANP receptor binding and desensitization were demonstrated in the A10 vascular smooth muscle cell (VSMC) line. Concomitantly, the ANP receptor coupled guanylate cyclase activity was reduced by the receptor down-regulation with ANP. The ANP stimulated cGMP accumulation is modulated by arginine-vasopressin, while the arginine-vasopressin mediated cAMP system remained unaffected by ANP. Results suggest negative coupling of arginine-vasopressin receptors to the guanylate cyclase activity, and indicate that the vasorelaxant activity of ANP might be regulated in part by arginine-vasopressin via specific receptor sites. PMID- 2898531 TI - Methotrexate analogues. 34. Replacement of the glutamate moiety in methotrexate and aminopterin by long-chain 2-aminoalkanedioic acids. AB - Eight previously unreported methotrexate (MTX) and aminopterin (AMT) analogues with the L-glutamate moiety replaced by DL-2-aminoalkanedioic acids containing up to 10 CH2 groups were synthesized from 4-amino-4-deoxy-N10-methylpteroic or 4 amino-4-deoxy-N10-formylpteroic acid. All the compounds were potent inhibitors of purified L1210 mouse leukemia dihydrofolate reductase (DHFR), with IC50's of 0.023-0.034 microM for the MTX analogues and 0.054-0.067 microM for the AMT analogues. The compounds were not substrates for, but were inhibitors of, partially purified mouse liver folylpolyglutamate synthetase (FPGS). Activity was correlated with the number of CH2 groups in the side chain. The IC50's for inhibition of cell growth in culture by the chain-extended MTX analogues were 0.016-0.64 microM against CEM human leukemic lymphoblasts and 0.0012-0.026 microM against L1210 mouse leukemia cells. However, the optimal chain length for growth inhibitory activity was species-dependent. Our results suggested that CEM cells were inhibited most actively by the analogue with nine CH2 groups, while L1210 cells were most sensitive to the analogue with six CH2 groups. Among the AMT analogues, on the other hand, the most active compound against L1210 cells was the one with nine CH2 groups, which had an IC50 of 0.000 65 microM as compared with 0.0046 microM for MTX and 0.002 microM for AMT. A high degree of cross resistance was observed between MTX and the chain-extended compounds in two MTX resistant cell lines, CEM/MTX and L1210/R81. All the MTX analogues were active against L1210 leukemia in mice on a qd X 9 schedule, with optimal increases in lifespan (ILS) of 75-140%. Notwithstanding their high in vitro activity, the AMT analogues were more toxic and less therapeutically effective than MTX analogues of the same chain length even though neither series of compounds possessed FPGS substrate activity. These MTX and AMT analogues are an unusual group of compounds in that they retain the dicarboxylic acid structure of classical antifolates yet are more lipophilic than the parent compounds because they have more CH2 groups and are almost equivalent in vivo to MTX on the same schedule even though they do not form polyglutamates. PMID- 2898532 TI - cis-4-Carboxy-6-(mercaptomethyl)-3,4,5,6-tetrahydropyrimidin-2(1 H)-one , a potent inhibitor of mammalian dihydroorotase. AB - A series of cis- and trans-4-carboxy-3,4,5,6-tetrahydropyrimidin-2(1H)-ones possessing either a carboxy, hydroxymethyl, or mercaptomethyl substituent at C-6 were prepared and tested for their ability to inhibit mammalian dihydroorotase. Of these compounds, only the cis-6-mercaptomethyl compound, cis-1, was found to be a potent competitive inhibitor of the enzyme (Ki = 140 nM at pH 7.4 and 8.5) when assayed in the direction of dihydro-L-orotate hydrolysis. These results suggest that the inhibition arises from the ligation of the thiolate to the zinc atom which is thought to be located in the enzyme's active site. Although analysis of cis-1 with 2,2'-dithiobis(5-nitrobenzoic acid) revealed significant loss of the free thiol group under enzymatic assay conditions, the addition of the reducing agent, dithiothreitol, to the enzymatic reaction mixtures afforded cis-1 complete protection against this chemical decomposition, as evidenced by lowering of the inhibition constant in the presence of dithiothreitol. Compound cis-1 had no significant antiproliferative activity against B16 melanoma cells in tissue culture, possibly due to the rapid decomposition of the compound or poor permeability into cells. PMID- 2898534 TI - Syntheses and gastric acid antisecretory properties of the H2-receptor antagonist. N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]thieno[3,4-d]isot hiazol 3-amine 1,1-dioxide and related derivatives. AB - The synthesis and gastric acid antisecretory properties of several N-substituted thieno[3,4-d]isothiazol-3-amine 1,1-dioxides and analogues are described. Two of the more potent compounds, N-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]thieno[3,4 d] isothiazol-3-amine 1,1-dioxide (6a) and N-[4-[3-(1 piperidinylmethyl)phenoxy]propyl]thieno[3,4-d] isothiazol-3-amine 1,1-dioxide, showed greater potencies as H2-receptor antagonists (in vitro) than ranitidine. They also had potent gastric acid antisecretory activities in vivo, inhibiting basal acid secretion in the rat, histamine-stimulated acid secretion in the dog, and food-stimulated acid secretion in the dog. These were selected for further pharmacological evaluation. PMID- 2898533 TI - Polycyclic aryl- and heteroarylpiperazinyl imides as 5-HT1A receptor ligands and potential anxiolytic agents: synthesis and structure-activity relationship studies. AB - A series of polycyclic aryl- and heteroarylpiperazinyl imides were prepared and tested in various receptor-binding and behavioral tests. Parameters measured included in vitro inhibition of D2 and 5-HT1A receptor binding, inhibition of apomorphine (APO) induced stereotyped and climbing behavior, and activity in blocking conditioned avoidance responding (CAR). Several compounds demonstrated moderate to high affinity for the 5-HT1A receptor binding site; compounds 27 and 36 containing the serotonin mimetic (o-methoxyphenyl)piperazinyl moiety and compounds 42 and 50 containing the 2-pyrimidinylpiperazinyl moiety displayed the highest affinity, being equal to that of the 5-HT1A agonist 8-OH-DPAT (Ki = 1-1.3 nM). In addition to affinity at 5-HT1A binding sites, many compounds were active in blocking CAR. Compound 34, 2-[4-[4-(2-pyrimidinyl)-1 piperazinyl]butyl]hexahydro-4,7-etheno-1H- cyclobut[f]isoindole-1,3(2H)-dione, demonstrated 3 times the activity of buspirone, blocking CAR in rats with an AB50 of 13 mg/kg. It also displayed high affinity for the 5-HT1A receptor (Ki = 16 nM), which is at least 20 times higher than its affinity for D2 (Ki = 345 nM) and 5-HT2 (Ki = 458 nM) receptors. Compound 34 was selected for further preclinical and pharmacokinetic evaluations for possible development as an anxiolytic agent. Structure-activity relationships within this series are discussed. PMID- 2898535 TI - Meiotic recombination in the beta globin gene cluster causing an error in prenatal diagnosis of beta thalassaemia. AB - In the course of a prenatal diagnosis for beta thalassaemia by linkage analysis of restriction fragment length polymorphisms, a homozygous beta thalassaemia fetus was misdiagnosed as beta thalassaemia trait. Extensive studies of the polymorphic sites within the beta globin gene cluster in all the members of the family resulted in the conclusion that the paternal chromosome 11 of the newborn was different from that expected. Paternity was confirmed by HLA typing and blood group studies. The analysis of another polymorphic locus on chromosome 11 within the family was in agreement with the possibility of a crossing over between the two paternal chromosomes in a region 5' to the beta gene, previously indicated to contain a 'hot spot' area for recombination. This report underlines the risk of performing prenatal diagnosis using restriction polymorphisms 5' to the beta gene. PMID- 2898536 TI - Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. Gastrointestinal Tumor Study Group. AB - Randomized trials of the Gastrointestinal Tumor Study Group have previously demonstrated enhanced survival of patients with locally unresectable pancreatic cancer treated with 5-fluorouracil in combination with radiation therapy compared with that of patients treated with radiation therapy alone. The present study compared the survival of patients treated with multidrug chemotherapy [streptozocin, mitomycin, and 5-fluorouracil (SMF)] versus radiation combined with 5-fluorouracil followed by the same three-drug SMF combination. In 43 patients randomly allocated between these two arms, an improved median survival for the combined-modality therapy (42 weeks) compared with chemotherapy alone (32 weeks) was demonstrated. Overall survival following this combined-modality treatment program (41% at 1 year) was significantly superior to that following SMF chemotherapy alone (19% at 1 year), by a two-tailed log rank test (P less than .02). Serial studies of the Gastrointestinal Tumor Study Group with patients with locally unresectable pancreatic adenocarcinoma have shown that combined modality therapy is superior to either optimal radiotherapy or chemotherapy alone. PMID- 2898537 TI - Isolation and nucleotide sequence of a cDNA clone encoding bovine adrenal tyrosine hydroxylase: comparative analysis of tyrosine hydroxylase gene products. AB - Investigations into the structure and mechanisms regulating the expression of the genes involved in catecholamine biosynthesis have led to the isolation of a cDNA coding for bovine adrenal tyrosine hydroxylase (TH). The 1,722 bp cDNA contains the complete coding sequence and 3' untranslated region of the TH mRNA. The nucleotide sequence of the cDNA and the deduced amino acid sequence were compared to those reported for rat and human TH. Bovine TH shares 85% and 84% amino acid sequence identity with that of rat and human TH, respectively. Alignment of the amino acid sequences of rat, bovine, and human TH reveals that 79% of the residues are identical in all three species, indicating a strong evolutionary conservation of enzyme structure. Moreover, three of the four putative phosphorylation sites located in the N-terminal region of TH are conserved in these animal species. There are, however, some interspecies differences in TH gene products. The 3' untranslated region of bovine TH mRNA is 56 and 97 nucleotides shorter than rat and human TH mRNA, respectively. Additionally, the bovine protein is 7 and 6 amino acids smaller than its rat and human homologues. All of the absent amino acid residues of bovine TH are missing from an alanine rich region in the N-terminal portion of the rat and human proteins (amino acids 51-68). Comparison of the size of bovine and rat TH mRNA and protein by northern blot and immunoblot analyses yielded differences consistent with those predicted from the nucleotide sequence data. PMID- 2898538 TI - Occult fractures in preschool children. AB - Five hundred consecutive radiographic examinations of acutely limping infants and toddlers were analyzed retrospectively. One hundred of the 500 (20%) had a fracture as the underlying etiology. Although the most common sites of involvement were the tibia/fibula (56 cases) and femur (30 cases), fractures in the pelvis and feet, notably the metatarsals (11 cases), also were seen. We therefore recommend obtaining radiographs of the pelvis and both lower extremities including the feet, when occult trauma is suspected and the exact area of injury cannot be pinpointed clinically. PMID- 2898539 TI - Substance abuse terminology. PMID- 2898540 TI - Amoebic pericardial effusion. PMID- 2898541 TI - [Clinical and epidemiological survey of adult T cell leukemia in Kanagawa Prefecture and HTLV-I infection in hemodialyzed patients]. PMID- 2898542 TI - [A case of adult T-cell leukemia with dual expressions of OKT4 and OKT8: clinical improvement by alpha interferon]. PMID- 2898543 TI - [Adult T-cell leukemia presenting scirrhous-like lesion in the stomach by X-ray examination]. PMID- 2898544 TI - [Adult T cell leukemia associated with antigen-positive cases due to blood transfusion]. PMID- 2898546 TI - [HTLV infection in patients with bone marrow transplantation]. PMID- 2898545 TI - [Measurement of ATLA antibody in patients with leukemia]. PMID- 2898547 TI - [Investigation into the actual conditions of the prevention of HTLV-I infections]. PMID- 2898548 TI - [Carrier detection of hemophilia A in the Japanese population by use of four intragenic and extragenic RFLPs]. PMID- 2898549 TI - [An autopsy case of adult T-cell leukemia with marked melena due to small intestine involvement]. PMID- 2898550 TI - [Chronic adult T-cell leukemia (ATL) complicating disseminated strongyloidiasis]. PMID- 2898551 TI - [Studies of severe pulmonary infection in patients with adult T-cell leukemia lymphoma]. PMID- 2898552 TI - [Chronic adult T cell leukemia with punched out osteolytic lesions: report of a case]. PMID- 2898553 TI - [Studies on immunoreactive somatostatin and gastrin contents in the same biopsy specimen of the gastric mucosa in patients with pernicious anemia]. PMID- 2898554 TI - [A case of aortitis syndrome (Takayasu's arteritis) associated with glomerulonephropathy mimicking lupus membranous glomerulonephropathy]. PMID- 2898555 TI - Selection of non-flagellated and non-piliated mutants from Pseudomonas aeruginosa strain TPB-1. PMID- 2898556 TI - Steroid metabolism in testes of patients with incomplete masculinization due to androgen insensitivity or 17 beta-hydroxysteroid dehydrogenase deficiency and normally differentiated males. AB - For purposes of establishing suitable controls in studies of patients with a suspected enzyme deficiency, activities of enzymes involved in the biosynthesis of testosterone were compared in testes of patients with androgen insensitivity syndrome (AIS) and normally differentiated males with carcinoma of the prostate (Ca prostate) or testis (Ca testis). Activities of 17,20-desmolase and of 3 beta hydroxysteroid dehydrogenase (3 beta-HSD) were higher in the testes of pre-, peri or postpubertal patients with AIS than in elderly men (58-80 yr) with Ca prostate. Activities of 17 beta-HSD (reductive direction) and 3 beta-HSD tended to be higher in peri- or postpubertal than in prepubertal patients with AIS. Activity of 3 beta-HSD was low in the patient with Ca testis. In a peripubertal (12 yr) patient with incomplete masculinization due to a severe deficiency of 17 beta-HSD, reductive activity of 17 beta-HSD was very low compared with that of patients with Ca prostate, Ca testis or AIS. In contrast, in testes from the younger sibling (4 yr), in whom the deficiency of 17 beta-HSD was less severe, 17 beta-HSD reduction of dehydroepiandrosterone was as high as that of men with Ca prostate, yet deficient in comparison with that of more closely age-matched patients with AIS. This emphasizes the desirability of using age-matched tissue for control purposes in enzyme studies. PMID- 2898557 TI - GH response to GRF (1-29) NH2 in female rats treated neonatally with estradiol benzoate or testosterone propionate. PMID- 2898558 TI - Angiographic studies of internal mammary artery grafts 11 years after coronary artery bypass grafting. AB - Of 99 consecutive patients with 101 internal mammary artery grafts, 91 of 97 hospital survivors (94%) underwent angiography 2 weeks after operation, 84 of 96 survivors (88%) after 1 year, 66 of 88 survivors (75%) after 5 years, and 37 of 69 survivors (54%) after 11 years (range 10 to 13 years). Thirty-five of the 37 patients who consented to a fourth postoperative angiographic study (95%, confidence limits 86% to 100%) still reported relieved angina 11 years after the operation, and seven patients (19%, confidence limits 5% to 33%) were completely free of symptoms. Angiographic findings in 30 patients with symptoms of angina were progression of the coronary artery disease in 22, (73%, confidence limits 56% to 91%), occluded or stenosed grafts in nine (30%, confidence limits 12% to 48%), and nonbypassed obstructions in six patients (20%, confidence limits 4% to 36%). The cumulative 11-year patency rate was 88%, confidence limits 81% to 95%, for internal mammary artery grafts and 61%, confidence limits 45% to 76% for saphenous vein grafts. Six of 18 saphenous vein grafts (33%, confidence limits 19% to 58%) occluded in the interval between 5 and 11 years after operation, and gross wall irregularities were observed in six of the 12 patent saphenous vein grafts. Unligated side branches and stenosis of the internal mammary artery did not prevent long-term graft patency. Internal mammary artery graft failures were related to technical errors during the operation and occurred when the internal mammary artery was used to bypass a low-grade coronary artery stenosis. In one patient, regression of a coronary artery stenosis was associated with a marked decrease in luminal size of the internal mammary artery graft before the 5-year follow-up. This single internal mammary artery graft became occluded in the interval between 5 and 11 years after the operation. Eleven of 36 internal mammary artery grafts (31%, confidence limits 14% to 47%) increased 15% to 40% in luminal diameter as a result of increased myocardial blood demand before the 11 year follow-up. PMID- 2898559 TI - Vasilii I. Kolesov. A pioneer of coronary revascularization by internal mammary coronary artery grafting. AB - Vasilii I. Kolesov, a cardiac surgeon from Leningrad, performed the first sutured internal mammary artery-coronary artery anastomosis on Feb. 25, 1964. He used the internal mammary artery pedicle (Kolesov's pedicle, Feb. 25, 1964) and described beadlike nodules and a dimpling of the epicardium over the atherosclerotic coronary artery (Kolesov's groove sign, Jan. 26, 1965). He introduced mechanical suturing to coronary artery surgery (March 22, 1967), internal mammary artery grafting for acute myocardial infarction (Feb. 5, 1968) and for unstable angina (May 17, 1968), and retrograde (Dec. 11, 1968) and bilateral (July 10, 1969) internal mammary artery grafts. Kolesov demonstrated early and long-term clinical and hemodynamic improvement with a 70% survival rate at 5 to 17 years' follow-up after internal mammary artery grafting (1967 to 1987). PMID- 2898560 TI - Vasilii I. Kolesov: pioneer in coronary revascularization. PMID- 2898561 TI - [Therapeutic results in Dupuytren contracture. Views on the surgical method and postoperative care]. PMID- 2898562 TI - [Management of Dupuytren contracture by Z-plasty and fasciectomy]. PMID- 2898563 TI - [The role of the minifixateur in hand surgery]. PMID- 2898564 TI - [Radiologic signs and biomechanical analysis of the progression of dysplastic coxarthrosis]. PMID- 2898565 TI - [Principle and initial results with the Charite Modular type SB cartilage disk endoprosthesis]. PMID- 2898566 TI - [The internal fixator: initial experiences in Hungary with the newest method for the management of thoraco-lumbar spinal injuries]. PMID- 2898567 TI - [Simultaneous fracture of the os capitatum and os scaphoideum]. PMID- 2898568 TI - [Incidence of tendon re-rupture and multiple tendon ruptures]. PMID- 2898569 TI - [Relation between the development of the acetabular roof and valgus re-rotation after varus derotation osteotomy of the femur]. PMID- 2898570 TI - [Results of MacIntosh hemiarthroplasty of the knee]. PMID- 2898571 TI - Determination of thyroid-binding inhibiting immunoglobulins using unextracted serum. PMID- 2898572 TI - Clinical utility of thyrotropin-receptor antibody assays: comparison of radioreceptor and bioassay methods. AB - Thyrotropin (thyroid-stimulating hormone or TSH)-receptor antibodies, important in the pathogenesis of Graves' disease, can be assayed by one of two methods: (1) bioassays that measure stimulation of thyroid cellular activity by patient immunoglobulins or (2) radioreceptor assays that measure inhibition of binding of labeled TSH to TSH receptors by the same substances. In this study, we report our experience with bioassay of thyroid-stimulating immunoglobulins (TSI) based on measurement of generation of cyclic adenosine monophosphate in a clone of the Fisher rat thyroid cell line (FRTL-5) in 279 patients, and we compare, in 163 consecutive samples, the results obtained by a radioreceptor assay for thyrotropin-binding inhibiting immunoglobulins (TBII). Among the untreated, hyperthyroid patients with Graves' disease, TSI were present in 95% (38 of 40), and TBII were present in 85% (17 of 20). In patients with euthyroid Graves' disease, TSI were found in 57% (16 of 28), and TBII were present in 41% (7 of 17). Of 49 nongoitrous and euthyroid controls, only 4% had TSI and 3% had TBII. Extremely high TSI indices were found in all patients who had pretibial dermopathy (N = 10) or severe Graves' ophthalmopathy (N = 19) requiring orbital decompression. We conclude that both assays are highly sensitive and specific in diagnosing Graves' disease. The TSI bioassay was more sensitive (P less than 0.001) than the TBII radioreceptor assay in detection of Graves' disease. In our experience, both assays have proved useful in the diagnosis of euthyroid Graves' disease with ophthalmopathy and atypical manifestations of hyperthyroid Graves' disease. PMID- 2898573 TI - Thyroid-stimulating hormone receptor antibodies--the calm after the storm after the calm? PMID- 2898574 TI - [Enzymes of cholestasis in myotonic dystrophy]. PMID- 2898575 TI - The effect of secretagogue selection on potency determinations for gastric acid antisecretory agents. AB - The most common treatment for gastric and duodenal ulcers is by suppressing the secretion of gastric acid by the parietal cells of the stomach. Two major categories of drugs can accomplish this specifically: histamine H2-receptor antagonist and (H+ + K+)ATPase inhibitors. Using a canine model of gastric acid secretion and either histamine or food as secretagogues, the effects of two drugs from each of these classes were investigated. The two H2-antagonists (ranitidine, Wy-45,727) demonstrated a significantly greater antisecretory potency when acid secretion was stimulated by histamine as compared to a food stimulus. Conversely, the (H+ + K+)ATPase inhibitors (omeprazole, timoprazole) were equipotent regardless of stimulus. PMID- 2898577 TI - [Diagnosis of adult type of polycystic kidney by means of genetic linkage analysis]. PMID- 2898578 TI - [Ecology of mosquito-borne infections in Fennoscandia--a review]. PMID- 2898576 TI - Anticatatonic effect of venoruton. AB - The protective effect of venoruton O-(beta-hydroxy-ethyl) rutoside, HR was investigated against drug induced catatonia in rats. Perphenazine, haloperidol, reserpine and meperidine produced frank catalepsy in rats. The cataleptic effect of these neuroleptics was significantly attenuated when the animals were pretreated with venoruton. The protective effect of venoruton is speculated to be due to its inhibitory action on superoxide formation and free radicals are considered to have a role in the neurotoxicity caused by the above agents. PMID- 2898579 TI - [Alpha-2-agonists in psychiatry--a review]. PMID- 2898580 TI - Diagnostic radionuclide imaging of amyloid: biological targeting by circulating human serum amyloid P component. AB - The specific molecular affinity of the normal plasma protein, serum amyloid P component (SAP), for all known types of amyloid fibrils was used to develop a new general diagnostic method for in-vivo radionuclide imaging of amyloid deposits. After intravenous injection of 123I-labelled purified human SAP there was specific uptake into amyloid deposits in all affected patients, 7 with systemic AL amyloid, 5 with AA amyloid, and 2 with beta 2M amyloid, in contrast to the complete absence of any tissue localisation in 5 control subjects. Distinctive high-resolution scintigraphic images, even of minor deposits in the carpal regions, bone marrow, or adrenals, were obtained. This procedure should yield much information on the natural history and the management of amyloidosis, the presence of which has hitherto been confirmed only by biopsy. Clearance and metabolic studies indicated that, in the presence of extensive amyloidosis, the rate of synthesis of SAP was greatly increased despite maintenance of normal plasma levels. Furthermore, once localised to amyloid deposits the 123I-SAP persisted for long periods and was apparently protected from its normal rapid degradation. These findings shed new light on the pathophysiology of amyloid and may have implications for therapeutic strategies based upon specific molecular targeting with SAP. PMID- 2898581 TI - Effect of bile salts and of fusidic acid on HIV-1 infection of cultured cells. AB - Bile salts completely inactivated human immunodeficiency virus type 1 (HIV-1) in vitro and, unexpectedly, completely destroyed all the cultured persistently HIV-1 infected T cells. Fusidic acid, which likewise possesses the properties of an anionic surfactant, inactivated HIV-1 only at concentrations toxic to uninfected cultured cells. Bile salts or their derivatives, and other anionic surfactants, could be of therapeutic value in HIV-1 infections. PMID- 2898582 TI - Antibody response to pre-S2 and hepatitis B virus induced liver damage. AB - Antibodies to the pre-S2 encoded sequence of the hepatitis B virus (HBV) envelope were detected in 83% of patients recovering from acute hepatitis B. Such antibodies were absent in cases showing chronic evolution and were found in less than 10% of chronic hepatitis B cases, with no relation to liver disease activity. In acute infection anti-pre-S2 became detectable when maximum liver damage had already occurred and was still detectable in 30% of the cases tested 5 7 years after recovery, as well as in 40% of healthy individuals with naturally acquired immunity to HBV. 10 out of 20 recipients of a plasma-derived, pre-S2 containing, HB vaccine acquired anti-pre-S2 and had no evidence of concurrent liver damage or of autoimmune reactions to human albumin or of suppression of the anti-HBs response. These findings indicate that the antibody response to pre-S2 is a marker of HBV clearance and has no role in the pathogenesis of HBV-related liver damage. PMID- 2898583 TI - A new treatment for urethral strictures. AB - A urethral stent, originally developed for endovascular use, was implanted into eight patients with urethral strictures after experimental studies in the canine urethra. The stent is woven in the form of a tubular mesh from surgical grade stainless steel wire and is self-expanding when released from its small-diameter delivery catheter. At follow-up 6 months to 1 year postoperatively (mean 8 months) all had a good calibre urethra. Urethroscopy showed complete epithelial covering of the implant at 4-6 months. PMID- 2898584 TI - Bone marrow transplantation in five children with sickle cell anaemia. AB - Five children with severe sickle cell anaemia underwent an HLA compatible allogeneic bone marrow transplantation. In four children the engraftment was rapid and sustained. The fifth child rejected the bone marrow graft and required a second bone marrow transplantation 62 days after the first one. The outcome was then uneventful. In all cases there was complete cessation of vaso-occlusive episodes and haemolysis. The haemoglobin electrophoretic pattern became similar to that of the donor (AA or AS) and cytogenetic studies in three patients confirmed the donor origin of bone marrow cells. PMID- 2898586 TI - What causes diabetic renal failure? PMID- 2898585 TI - Relaxin as an aetiological factor in diabetic embryopathy. AB - Relaxin, an insulin homologue, has effects on collagen resembling those of certain teratogenic agents. It is suggested that diabetic embryopathy could be due to disturbances of relaxin secretion during fetal organogenesis. PMID- 2898587 TI - Cryptococcosis and AIDS. PMID- 2898588 TI - Virus diagnostic scanning electronmicroscopy. PMID- 2898589 TI - Disposable extended-wear contact lenses. PMID- 2898590 TI - Drug delivery in red blood cells. PMID- 2898591 TI - Pontine and extrapontine myelinolysis following rapid correction of hyponatraemia. AB - Central pontine and extrapontine myelinolysis is caused by the rapid correction of hyponatraemia. Acceptance of this concept has been impeded by recent reports attributing myelinolysis to uncorrected hyponatraemia, overcorrection of hyponatraemia, or hypoxia. Several new names have been proposed for this disease, but all are less specific than pontine and extrapontine myelinolysis. This proliferation of terminology is unnecessary and adds to the confusion surrounding the aetiology of myelinolysis. PMID- 2898592 TI - Pulmonary embolectomy: its place in the management of pulmonary embolism. PMID- 2898593 TI - Outcome of confirmed periconceptional maternal rubella. AB - 61 pregnant women in whom confirmed rubella occurred from 5 weeks before to 6 weeks after the last menstrual period (LMP) were followed up prospectively. In 39, the pregnancy was terminated and the fetal tissues or mixed products of conception were examined for rubella virus. In 22, the pregnancy continued to term and cord serum was tested for specific IgM antibody. No evidence of intrauterine infection was found in 38 pregnancies in which the mother's rash appeared before, or within 11 days after, the last menstrual period. The shortest interval at which fetal infection occurred was when the rash appeared 12 days after the last menstrual period. All 10 pregnancies in which the rash appeared 3 6 weeks after the last menstrual period resulted in fetal infection: 4 of these pregnancies went to term, and all 4 infants were damaged. The risk to the fetus when rubella occurs before the mother's last menstrual period is probably negligible. PMID- 2898594 TI - Rational programme for screening travellers for antibodies to hepatitis A virus. AB - A blood test and a saliva test for antibody to hepatitis A virus (anti HAV) were offered to British travellers seeking human normal immunoglobulin (HNIG) prophylaxis. The specimens were tested by an IgG capture and a competitive radioimmunoassay (GACRIA, COMPRIA). By GACRIA 211 subjects were anti-HAV positive and 358 anti-HAV negative on both serum and saliva. 10 other seropositive subjects had weakly positive saliva reactions. There were three discrepant results. For the population investigated HNIG use could be minimised at no extra cost by first testing the saliva of those greater than 40 years old, frequent or long-stay travellers, those born in HAV endemic areas, and those with a history of jaundice. Of the 51% of travellers tested for these reasons 20% were anti-HAV positive. They made up 76% of all those with antibody. PMID- 2898595 TI - Polycythaemia vera can present with aquagenic pruritus. PMID- 2898596 TI - Six deaths from measles. PMID- 2898597 TI - Penicillin-resistant pneumococci. PMID- 2898598 TI - Penicillin-resistant strains of Neisseria meningitidis in Spain. PMID- 2898600 TI - Tetracycline-resistant meningococci. PMID- 2898599 TI - HIV seroconversion with progressive disease in health care worker after needlestick injury. PMID- 2898601 TI - Increased frequency of haemarthroses in haemophilic patient treated with zidovudine. PMID- 2898602 TI - Severe hypocalcaemia in AIDS patients treated with foscarnet and pentamidine. PMID- 2898603 TI - In vitro inactivation of HIV-1 by contraceptive sponge containing nonoxynol-9. PMID- 2898604 TI - Disseminated intravascular coagulation associated with group A streptococcal infection in pregnancy. PMID- 2898606 TI - Detection of drugs in urine of body-packers. PMID- 2898605 TI - Cyclosporin-associated cerebral lesions in liver transplantation. PMID- 2898607 TI - Indexing bibliographic data bases. PMID- 2898608 TI - Oronasal obstruction, lung volumes, and arterial oxygenation. PMID- 2898609 TI - Red-cell surface charge in patients with nephrotic syndrome. PMID- 2898610 TI - Failure of intravenous immunoglobulin to affect cytotoxic T lymphocyte responses. PMID- 2898611 TI - Differences between benzodiazepines. PMID- 2898612 TI - Season of birth, year of birth, and arthritic disease in later life. PMID- 2898613 TI - Non-tuberculous mycobacteria in gastrointestinal biopsy specimens. PMID- 2898614 TI - Deletions of muscle mitochondrial DNA. PMID- 2898615 TI - Gain of antibiotic sensitivity accompanying emergence of clinical ciprofloxacin resistance. PMID- 2898616 TI - Human herpesvirus 6 and exanthem subitum. PMID- 2898617 TI - Antimitochondrial-positive but anti-M2-negative primary biliary cirrhosis. PMID- 2898618 TI - Overuse syndrome. PMID- 2898619 TI - Cold-chain breaks in Africa. PMID- 2898620 TI - Association of cytomegalovirus infection with autoimmune type 1 diabetes. AB - The lymphocytes from 59 newly diagnosed type 1 diabetic patients and 38 normal control subjects were examined for the presence of human cytomegalovirus (CMV) genome by molecular hybridizations with human CMV specific probe. The CMV specific viral genome was found in 13 (22%) of 59 diabetic patients, but in 1 (2.6%) of 38 control subjects. Of the patients, 39% had islet cell antibody (ICA) and 41% had cytotoxic beta cell surface antibody (CBSA) in their serum; of the controls the corresponding rates were 2.6% and 2.6%. 62% and 69% of CMV genome positive patients had ICA and CBSA, respectively, compared with 33% and 33% of CMV genome-negative patients. The single CMV genome-positive control subject did not have either ICA or CBSA whereas only 1 of the 37 CMV genome-negative control subjects had ICA. The strong correlation between CMV genome and islet cell autoantibodies detected in diabetic patients suggests that persistent CMV infections may be relevant to pathogenesis in some cases of type 1 diabetes. PMID- 2898621 TI - Patent foramen ovale in young stroke patients. AB - The prevalence of patent foramen ovale in patients presenting with non haemorrhagic stroke or transient ischaemic attacks under the age of 40 years was determined by contrast echocardiography. Studies were performed at rest and with a Valsalva manoeuvre in 40 stroke patients and in an age and sex matched control group. Right-to-left shunting was found in 20 (50%) of the stroke patients and 6 (15%) of the controls (p less than 0.001). Paradoxical embolism through a patent foramen ovale may be an under-recognised cause of stroke in young adults. PMID- 2898624 TI - Need we poison the elderly so often? PMID- 2898623 TI - Yin and yang in vasomotor control. PMID- 2898622 TI - Rapid recurrence of mania following abrupt discontinuation of lithium. AB - Fourteen patients with a history of mania satisfying DSM-III criteria were entered into a randomised double-blind placebo-controlled crossover trial, spending four weeks on each of lithium and placebo. All patients had been well and stable on lithium for at least 18 months and were not taking any other psychotropic drugs. Seven patients (50%) had a relapse of their manic illness and a further two had to be withdrawn because they recognised signs of incipient relapse. One of these became overtly manic after restarting lithium. The seven definite and the two possible relapses occurred in the placebo phase; this finding was unlikely to have arisen by chance. The relapses started 13-19 days after placebo substitution. These results have important implications in the management of lithium prophylaxis by all doctors, particularly those who, for any reason, are considering withdrawal of lithium from their patients. PMID- 2898625 TI - Trans-tracheal oxygen. PMID- 2898626 TI - Pacemakers to make the heart beat faster with exercise. PMID- 2898627 TI - Sedation, analgesia, and intranasal sufentanil. PMID- 2898628 TI - Sodium intake, body sodium, and sodium excretion. PMID- 2898629 TI - Investigation of inborn errors of metabolism in unexpected infant deaths. PMID- 2898630 TI - Subgroup analysis. PMID- 2898631 TI - Egypt. Medical care, public and private. PMID- 2898632 TI - First seizure in adult life. PMID- 2898633 TI - Listeria in cook-chill food. PMID- 2898634 TI - Cholesterol in Indian ghee. PMID- 2898635 TI - "Yellowfever" in eastern Nigeria. PMID- 2898637 TI - Fetal "soap" addiction. PMID- 2898636 TI - Quality of life on angina therapy: a randomised controlled trial of transdermal glyceryl trinitrate against placebo. AB - In a randomised controlled trial in 427 men with chronic stable angina continuous use of 5 mg transdermal glyceryl trinitrate (GTN) showed no advantage over placebo in terms of efficacy (anginal attack rates and sublingual GTN consumption) or quality of life (as measured with the sickness impact profile and a health index of disability). Patients on the active drug reported headaches more frequently than patients on placebo, and a higher proportion of them withdrew from the trial because of headache. Quality-of-life measurements showed a significant adverse effect of active treatment, principally in the social interaction dimension of the sickness impact profile. A similar effect was observed in placebo patients when crossed to active treatment in a 4-week single blind period. The results suggest no benefit in the relief of chest pain from 5 mg transdermal GTN when used continuously. PMID- 2898639 TI - Drug users, AIDS, and the government response. PMID- 2898638 TI - Long-term psychiatric sequelae of physical and sexual abuse of females. PMID- 2898640 TI - AIDS, condoms, and prisons. PMID- 2898641 TI - A small outbreak of HIV infection among commercial plasma donors. PMID- 2898642 TI - Breast feeding and premature babies. PMID- 2898643 TI - Coagulation factor VIII concentrates and the marketplace. PMID- 2898644 TI - Cutaneous reactions to aluminium in vaccines: an avoidable problem. PMID- 2898645 TI - Solitary rectal ulcer. PMID- 2898646 TI - Children, paediatrics and South Africa. PMID- 2898647 TI - Ethics of preventive medicine. PMID- 2898648 TI - Erythromycin propionate and estolate. PMID- 2898649 TI - New category of drug allergy. PMID- 2898650 TI - Shigella diarrhoea and treatment. PMID- 2898651 TI - Uraemic thrombocytopathy and parathyroid hormone. PMID- 2898652 TI - Predicting insulin-dependent diabetes. PMID- 2898653 TI - Q-T interval syndromes. PMID- 2898654 TI - Leukaemia in electrical workers in New Zealand: a correction. PMID- 2898655 TI - Myocardial injury after interleukin-2 therapy. PMID- 2898657 TI - Differentiation of glomerular and non-glomerular haematuria. PMID- 2898656 TI - Ursodeoxycholic acid for cholestatic diseases. PMID- 2898658 TI - Indices of angina. PMID- 2898659 TI - Non-meningococcal purpuric sepsis. PMID- 2898660 TI - Congenital abnormalities and congenital hypothyroidism. PMID- 2898661 TI - Y chromosome and sex determination. PMID- 2898662 TI - Synthetic oligonucleotides as diagnostic probes for rhinoviruses. PMID- 2898664 TI - Excessive hours of work. PMID- 2898663 TI - IVth international AIDS conference. PMID- 2898665 TI - A second genetic locus for autosomal dominant polycystic kidney disease. AB - Hitherto, mutations that lead to autosomal dominant adult-type polycystic kidney disease have been found to be linked to the alpha-globin genes on the short arm of chromosome 16. In an Italian family, absence of linkage between the disease mutation and alpha-globin indicates that the condition can be caused by mutations in a second gene. The clinical features of the disease in this Italian family are indistinguishable from those found in the "linked" families. The finding that there are two polycystic kidney disease genes means that linkage must be demonstrated independently in each family before predictive tests with DNA probes can be used reliably. PMID- 2898666 TI - Aspirin, expectations, and the heart. PMID- 2898668 TI - Myalgic encephalomyelitis, or what? PMID- 2898667 TI - Vocal-cord paresis in infants: another use for continuous insufflation of the pharynx. PMID- 2898669 TI - Interferon production in postviral fatigue syndrome. PMID- 2898670 TI - Prenatal diagnosis of cystic fibrosis by DNA amplification for detection of KM-19 polymorphism. PMID- 2898672 TI - Novel viruses in human faeces. PMID- 2898671 TI - Same-day, first-trimester antenatal diagnosis for cystic fibrosis by gene amplification. PMID- 2898673 TI - 99mTc-HMPAO scanning in focal encephalitis. PMID- 2898675 TI - Sleeping position and SIDS. PMID- 2898674 TI - Piezoelectric lithotripsy of gallstones. PMID- 2898677 TI - Acceptability of medical pregnancy termination. PMID- 2898676 TI - Which salt of pentamidine? The case for dosage in substance units. PMID- 2898678 TI - Hepatitis B and blood transfusion. PMID- 2898679 TI - Health warnings and alcoholic drinks. PMID- 2898680 TI - Remedies for tropical diseases. PMID- 2898681 TI - Heatstroke and armed forces training. PMID- 2898682 TI - HIV and aplastic anaemia. PMID- 2898683 TI - HIV antigen testing. PMID- 2898684 TI - HIV testing without permission. PMID- 2898685 TI - Bovine viral diarrhoea. PMID- 2898686 TI - Surgical audit and carotid endarterectomy. PMID- 2898687 TI - Adhesive dressing allergy. PMID- 2898688 TI - Improving elective referral rate for abdominal aortic aneurysm. PMID- 2898689 TI - Meningococcal rash. PMID- 2898690 TI - Raised renal venous pressure: direct cause of renal sodium retention in cirrhosis? PMID- 2898691 TI - Legionella: a case for culture. PMID- 2898692 TI - Ethambutol and the eye. PMID- 2898693 TI - Cerebellar stroke. PMID- 2898694 TI - Treatment of adult systemic mastocytosis with a PAF-acether antagonist BN52063. PMID- 2898695 TI - Importance of HLA antigen splits for kidney transplant matching. AB - Whether matching for HLA antigen "splits" results in better transplant outcome than matching for "broad" HLA antigens was investigated in 30,000 first cadaver kidney transplants. At three years, there was an 18% difference between the survival rates of grafts with 0 or 4 mismatches among transplants typed for HLA-A and B antigen splits whereas the difference in transplants typed for broad antigens was only 2%. Analysis of HLA-A, B antigens together with HLA-DR antigens showed an even greater advantage of matching for antigen splits: the difference in survival at three years between grafts with 0 or 6 mismatches for HLA-A, B, DR was 31% when antigen splits were analysed, in contrast to a 6% difference with broad antigens. These results indicate that typing for HLA antigen splits is important in renal transplantation, that the potential benefit of HLA matching in renal transplantation is greater than currently accepted, and that HLA typing and kidney allocation routines must be refined in order to exploit this potential. PMID- 2898697 TI - Adverse effect of early high-dose adrenaline on outcome of ventricular fibrillation. AB - Resuscitation for cardiac arrest was monitored over 4 years to examine the effect on survival of a change in the ventricular fibrillation (VF) protocol to include the routine early use of "high-dose" intravenous or transbronchial adrenaline. A significant reduction in the immediate survival of patients with VF was seen when the protocol was changed (22% after the change, 43% before). Prior predictors of poor response were similar in each group, except for the number of witnessed arrests, delay until cardiopulmonary resuscitation, and occurrence of endotracheal intubation, but multiple logistic regression showed the use of adrenaline to be an independent predictor of outcome. Early high-dose adrenaline was associated with a reduction in immediate survival in patients with persistent VF. PMID- 2898696 TI - Single dose phenobarbitone prevents convulsions in cerebral malaria. AB - 48 patients over 6 years of age with strictly defined cerebral malaria were randomised to receive either a single intramuscular injection of phenobarbitone (3.5 mg/kg) or placebo in a double-blind, placebo-controlled study. Phenobarbitone significantly reduced the incidence of subsequent convulsions from 54% to 12.5%, without adverse effects. A single intramuscular injection of phenobarbitone is a simple, cheap, and effective method for prevention of convulsions in cerebral malaria. PMID- 2898698 TI - Long-term follow-up of 71 patients with thunderclap headache mimicking subarachnoid haemorrhage. AB - Seventy-one patients with sudden, severe, and unusual headache, but with normal computerised tomographic scan and cerebrospinal fluid, were followed for an average of 3.3 years. Twelve patients (17%) had identical recurrences, but again without evidence of subarachnoid haemorrhage. Findings on cerebral angiography, performed in four patients after the first attack and in two patients after recurrent episodes, were normal. Thirty-one (44%) of the seventy-one patients subsequently had regular episodes of tension headache or common migraine. If the computerised tomographic scan and cerebrospinal fluid findings are normal, this type of headache can be regarded as a benign symptom, and cerebral angiography is not indicated. PMID- 2898699 TI - Alpha-interferon therapy for essential thrombocythaemia. AB - 18 patients with symptomatic essential thrombocythaemia were treated with recombinant alpha interferon (2a or 2b). Subcutaneous dosage regimens, which were well-tolerated, selectively lowered the platelet count and relieved symptoms in all patients, whether previously treated or untreated. Recombinant alpha interferon may offer a non-leukaemogenic alternative therapy for these patients. PMID- 2898700 TI - Enhanced tumour necrosis factor and interleukin-1 in fulminant hepatic failure. AB - Sepsis and endotoxaemia are common in fulminant hepatic failure (FHF) and may contribute to multisystem disease in such patients. Tumour necrosis factor (TNF) is a probable mediator of endotoxic shock and infusion of this monokine into animals causes multi-organ failure that shares features with FHF. In patients with FHF, TNF production was increased and correlated closely with activity of interleukin-1, another cytokine that is released by monocytes/macrophages in response to infection and endotoxin and is produced in increased quantities in FHF. Interleukin-2 activity was impaired in FHF and correlated negatively with TNF production. PMID- 2898702 TI - The NHS at 40: skeletons at the birthday feast. PMID- 2898701 TI - Genesis of breast cancer is in the premenopause. AB - In Britain and other high-risk countries, about a third of patients with breast cancer are premenopausal at diagnosis. In the remainder, tumour initiation might have occurred in the premenopause, even though the clinical presentation was late in life. This possibility has important implications for breast cancer prevention and screening. The relations between the patient's age and tumour kinetics, prognosis, oestrogen receptors, and environmental X-ray carcinogenesis were studied, together with the age-related protection afforded by pregnancy. The findings support the hypothesis that breast cancer is initiated in the premenopause. PMID- 2898703 TI - Headaches and subarachnoid haemorrhage. PMID- 2898705 TI - Another Savage? PMID- 2898706 TI - Isolated reduction of residual volume. PMID- 2898704 TI - The Philadelphia chromosome and chronic myeloid leukaemia. PMID- 2898708 TI - Changing prevalence of juvenile-onset diabetes mellitus. AB - Comparison of age-specific prevalence of juvenile-onset diabetes mellitus between 1946 and 1958 British cohort birth studies (up to the ages of 26 and 23, respectively) suggests that the overall prevalence of diabetes in young life has not increased, but the disease is manifest at an earlier age in susceptible individuals. PMID- 2898707 TI - Value of necropsy in acquired immunodeficiency syndrome. AB - Necropsy findings in 101 adult patients with the acquired immunodeficiency syndrome (AIDS) from two metropolitan hospitals were compared retrospectively with the antemortem clinical diagnoses. 94% of the patients were male and 68% were homosexual or bisexual. 75 (74%) patients had AIDS-related diseases at necropsy that were not suspected clinically. The commonest of the unsuspected AIDS-related diseases were cytomegalovirus infection (49% of all cases), systemic fungal infection (20%), systemic Kaposi's sarcoma (14%), Mycobacterium avium intracellulare infection (11%), and systemic herpes infection (9%). Cryptococcal infection and cytomegalovirus retinitis were always diagnosed antemortem; and Pneumocystis carinii pneumonia went undiagnosed in only 5 of 58 (9%) patients who had proven infection either clinically or at necropsy. 8 patients who died with fungal pneumonia had undergone bronchoscopy; however, in only 1 patient was it diagnosed antemortem. Tuberculosis was undiagnosed in 4 patients. 4 cases of central nervous system lymphoma diagnosed only at necropsy had been treated empirically for toxoplasmosis. Bacterial pneumonias contributed considerably to mortality in 30% of the patients. PMID- 2898710 TI - Meta-analysis. PMID- 2898709 TI - Blood disorders and suicide in patients taking mianserin or amitriptyline. AB - 26,781 patients who had been prescribed mianserin and 42,082 prescribed amitriptyline were followed up by means of a questionnaire addressed to their general practitioners. No patient had aplastic anaemia, agranulocytosis, or leucopenia severe enough to endanger life, and in only 2 patients in each group was a causal association likely. If either drug dose cause leucopenia, the incidence is likely to be in the range of 1 in 10,000 to 1 in 100,000 patients. Among patients who were reported to have attempted suicide, 56 of 246 survivors of amitriptyline overdoses required intensive care, compared with none of 92 patients who overdosed with mianserin. 4 patients who overdosed with amitriptyline alone died, compared with none of the patients who overdosed with mianserin alone. Both drugs are associated with a low risk of blood disorders, but mianserin is appreciably safer than amitriptyline because of its low toxicity in overdosage. PMID- 2898711 TI - Thrombin/antithrombin-III complex level as early predictor of reocclusion after successful thrombolysis. PMID- 2898712 TI - Community-based treatment with ivermectin. PMID- 2898713 TI - Peppermint oil. PMID- 2898714 TI - Indwelling intravenous catheter in a young haemophiliac. PMID- 2898715 TI - Opiate-prostaglandin interactions in the regulation of insulin secretion from rat islets of Langerhans in vitro. AB - The inadequate insulin secretory response to glucose stimulation in non-insulin dependent diabetes has been attributed to many factors including high PGE2 levels blunting the secretory response, and to the existence of inhibitory opiate activity in vivo. The purpose of the present work was to see if there was a connection between these two independent theories. Radioimmunoassayable PGE2 in islets of Langerhans was found to be proportional to islet number and protein content and was typically 4 to 5pg/micrograms islet protein. Indomethacin (2.8 X 10(-5) M), sodium salicylate (1.25 X 10(-3) M) and chlorpropamide (7.2 X 10(-5) M) all lowered islet PGE2 levels and stimulated insulin release in vitro. Dynorphin (1-13), stimulated insulin release at a concentration of 6 X 10(-9) M, while lowering islet PGE2. Conversely, at a higher concentration, (6 X 10(-7) M), dynorphin had no stimulatory effect on insulin secretion and did not lower PGE2 levels in islets or in the incubation media. The stimulatory effects of dynorphin and sodium salicylate on insulin secretion were blocked by exogenous PGE2 (10(-5) M). PGE2 at a lower concentration (10(-9) M) did not exert any inhibitory effect on dynorphin- or sodium salicylate-induced insulin release. This concentration of exogenous PGE2 stimulated insulin release in the presence of 6mM glucose. Results from these experiments suggest that since an opioid peptide can lower endogenous PGE2 production in islets and since the stimulatory effects of the opioid peptide are reversed by exogenous PGE2 there may be interactions between these two modulators of insulin secretion. PMID- 2898716 TI - Quantitative autoradiography of [3H]CTOP binding to mu opioid receptors in rat brain. AB - [3H]H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 ([3H]CTOP), a potent and highly selective mu opioid antagonist, was used to localize the mu receptors in rat brain by light microscopic autoradiography. Radioligand binding studies with [3H]CTOP using slide-mounted tissue sections of rat brain produced a Kd value of 1.1 nM with a Bmax value of 79.1 fmol/mg protein. Mu opioid agonists and antagonists inhibited [3H]CTOP binding with high affinity (IC50 values of 0.2-2.4 nM), while the delta agonist DPDPE, delta antagonist ICI 174,864, and kappa agonist U 69, 593 were very weak inhibitors of [3H]CTOP binding (IC50 values of 234-3631 nM). Light microscopic autoradiography of [3H]CTOP binding sites revealed regions of high density (nucleus of the solitary tract, clusters in the caudate-putamen, interpeduncular nucleus, superior and inferior colliculus, subiculum, substantia nigra zona reticulata, medial geniculate, locus coeruleus and dorsal motor nucleus of the vagus) and regions of moderate labeling (areas outside of clusters in the caudate-putamen, cingulate cortex, claustrum and nucleus accumbens). The cerebral cortex (parietal) showed a low density of [3H]CTOP binding. PMID- 2898717 TI - Effect of subcutaneous injection of a long-acting analogue of somatostatin (SMS 201-995) on plasma thyroid-stimulating hormone in normal human subjects. AB - SMS 201-995 (SMS), a synthetic analogue of somatostatin (SRIF) has been shown to be effective in the treatment of the hypersecretion of hormones such as in acromegaly. However, little is known about the effects of SMS on the secretion of thyroid-stimulating hormone (TSH) in normal subjects. In this study, plasma TSH was determined with a highly sensitive immunoradiometric assay, in addition to the concentration of SMS in plasma and urine with a radioimmunoassay, following subcutaneous injection of 25, 50, 100 micrograms of SMS (4 subjects/dose) or a placebo (6 subjects) to normal male subjects, at 0900 h after an overnight fast. The plasma concentrations of SMS were dose-responsive and the peak levels were 1.61 +/- 0.09, 4.91 +/- 0.30 and 8.52 +/- 1.18 ng/ml, which were observed at 30, 15 and 45 min after the injection of 25, 50 and 100 micrograms of SMS, respectively. Mean plasma disappearance half-time of SMS was estimated to be 110 +/- 3 min. Plasma TSH was suppressed in a dose dependent manner and the suppression lasted for at least 8 hours. At 8 hours after the injection of 25, 50 and 100 micrograms of SMS, the plasma TSH levels were 43.8 +/- 19.4, 33.9 +/- 9.4 and 24.9 +/- 3.2%, respectively, of the basal values. The results suggest that SMS suppresses secretion of TSH from the normal thyrotrophs in man and thus also that attention should be paid to possible hypothyroidism during the long-term treatment of patients such as those with acromegaly with this potent analogue of SRIF. PMID- 2898718 TI - Hypothermic response produced by manassantin A, a novel neuroleptic agent. AB - Manassantin A (MNS-A), a novel neolignoid, neutral compound shown to possess neuroleptic properties, causes hypothermic response in male and female mice of CD 1 strain when administered by the intra-cerebroventricular (icv), (0.1, 1.0, 3.2, 10 micrograms/mouse), intraperitoneal (ip), (0.1, 0.32, 1.0, 3.2 mg/kg) and oral (0.5, 1.6, 5.0, 16 mg/kg) routes. The hypothermia was found to be dose and time dependent, the maximum decrease of temperature being observed by the icv route (P less than 0.001) after 2 hours. However, ip and oral administration of lower and middle order doses were not very effective but higher doses caused significant (P less than 0.001) reduction of body temperature. The centrally-induced hypothermic response by MNS-A may give future leads as a screening model for antidepressant drugs and can be a useful tool for manipulating physiological and pharmacological processes to understand the central thermoregulatory functions. PMID- 2898719 TI - International Congress of Medical Librarians, Tokyo--1985. PMID- 2898720 TI - Insulinoma in a patient with the MEN type I syndrome. PMID- 2898721 TI - [History of nurses' training in the USSR]. PMID- 2898722 TI - [All-around programs of the specialties--a scientific basis for making study plans and standard programs in medical and pharmaceutical schools]. PMID- 2898723 TI - [Beta blockers in acute and chronic phases of myocardial infarction]. PMID- 2898724 TI - [Treatment of chronic obstructive bronchitis with almitrine]. PMID- 2898725 TI - Treatment of Physalia physalis envenomation. PMID- 2898726 TI - [Description of a case: Beckwith-Wiedemann syndrome]. PMID- 2898727 TI - Three sequence-specific DNA-protein complexes are formed with the same promoter element essential for expression of the rat somatostatin gene. AB - We identified three sequence-specific DNA-protein complexes which are formed after in vitro binding of nuclear extracts, derived from neuronal (CA-77, rat brain) or non-neuronal (HeLa) cells, to positions -70 to -29 of the rat somatostatin promoter. The protein(s) responsible for the formation of the three sequence-specific complexes was fractionated from rat brain whole cell extracts by DEAE-Sepharose chromatography. The critical contact residues of the factor(s) in each complex, as determined by methylation interference analyses, are located within positions -59 to -35, which is protected from DNase I digestion; these include the G residues of a TGACGTCA consensus also found in the cAMP-responsive human enkephalin (positions -105 to -76) and E1A-inducible adenovirus type 5 E3 (positions -72 to -42) promoters. Competition assays with these heterologous promoters reveal that the factor(s) of each complex displays approximately 50 fold greater affinity for the somatostatin promoter-binding site. Synthetic oligonucleotides spanning positions -70 to -29 of the somatostatin promoter and containing single-base substitutions of the G residues in the TGACGTCA consensus were utilized in competition assays. The G residues located in the center of the module are the most critical determinants in the formation of the three sequence specific complexes. Deletions disrupting the TGACGTCA consensus abolish not only formation of the three complexes in vitro but also expression of the somatostatin promoter in vivo, suggesting that formation of one or more of these complexes is essential for transcription of the rat somatostatin gene. PMID- 2898728 TI - Determinants of mRNA stability in Dictyostelium discoideum amoebae: differences in poly(A) tail length, ribosome loading, and mRNA size cannot account for the heterogeneity of mRNA decay rates. AB - As an approach to understanding the structures and mechanisms which determine mRNA decay rates, we have cloned and begun to characterize cDNAs which encode mRNAs representative of the stability extremes in the poly(A)+ RNA population of Dictyostelium discoideum amoebae. The cDNA clones were identified in a screening procedure which was based on the occurrence of poly(A) shortening during mRNA aging. mRNA half-lives were determined by hybridization of poly(A)+ RNA, isolated from cells labeled in a 32PO4 pulse-chase, to dots of excess cloned DNA. Individual mRNAs decayed with unique first-order decay rates ranging from 0.9 to 9.6 h, indicating that the complex decay kinetics of total poly(A)+ RNA in D. discoideum amoebae reflect the sum of the decay rates of individual mRNAs. Using specific probes derived from these cDNA clones, we have compared the sizes, extents of ribosome loading, and poly(A) tail lengths of stable, moderately stable, and unstable mRNAs. We found (i) no correlation between mRNA size and decay rate; (ii) no significant difference in the number of ribosomes per unit length of stable versus unstable mRNAs, and (iii) a general inverse relationship between mRNA decay rates and poly(A) tail lengths. Collectively, these observations indicate that mRNA decay in D. discoideum amoebae cannot be explained in terms of random nucleolytic events. The possibility that specific 3' structural determinants can confer mRNA instability is suggested by a comparison of the labeling and turnover kinetics of different actin mRNAs. A correlation was observed between the steady-state percentage of a given mRNA found in polysomes and its degree of instability; i.e., unstable mRNAs were more efficiently recruited into polysomes than stable mRNAs. Since stable mRNAs are, on average, "older" than unstable mRNAs, this correlation may reflect a translational role for mRNA modifications that change in a time-dependent manner. Our previous studies have demonstrated both a time-dependent shortening and a possible translational role for the 3' poly(A) tracts of mRNA. We suggest, therefore, that the observed differences in the translational efficiency of stable and unstable mRNAs may, in part, be attributable to differences in steady-state poly(A) tail lengths. PMID- 2898729 TI - Assembly of a polyadenylation-specific 25S ribonucleoprotein complex in vitro. AB - Extracts from HeLa cell nuclei assemble RNAs containing the adenovirus type 2 L3 polyadenylation site into a number of rapidly sedimenting heterodisperse complexes. Briefly treating reaction mixtures prior to sedimentation with heparin reveals a core 25S assembly formed with substrate RNA but not an inactive RNA containing a U----C mutation in the AAUAAA hexanucleotide sequence. The requirements for assembly of this heparin-stable core complex parallel those for cleavage and polyadenylation in vitro, including a functional hexanucleotide, ATP, and a uridylate-rich tract downstream of the cleavage site. The AAUAAA and a downstream U-rich element are resistant in the assembly to attack by RNase H. The poly(A) site between the two protected elements is accessible, but is attacked more slowly than in naked RNA, suggesting that a specific factor or secondary structure is located nearby. The presence of a factor bound to the AAUAAA in the complex is independently demonstrated by immunoprecipitation of a specific T1 oligonucleotide containing the element from the 25S fraction. Precipitation of this fragment from reaction mixtures is blocked by the U----C mutation. However, neither ATP nor the downstream sequence element is required for binding of this factor in the nuclear extract, suggesting that recognition of the AAUAAA is an initial event in complex assembly. PMID- 2898732 TI - Fatal pulmonary lipid embolism associated with taxol therapy. PMID- 2898733 TI - Costs and effectiveness of routine therapy with long-term beta-adrenergic antagonists after acute myocardial infarction. AB - We analyzed the costs and effectiveness of routine therapy with beta-adrenergic antagonists in patients who survived an acute myocardial infarction. On the basis of data pooled from the literature, this form of therapy resulted in a 25 percent relative reduction annually in the mortality rate for years 1 to 3 and a 7 percent relative reduction for years 4 to 6 after a myocardial infarction. The estimated cost of six years of routine beta-adrenergic-antagonist therapy to save an additional year of life was $23,400 in low-risk patients, $5,900 in medium risk patients, and $3,600 in high-risk patients, assuming that the entire benefit of earlier treatment is lost immediately after six years. Under a more likely assumption--that the benefit of six years of treatment wears off gradually over the subsequent nine years--the estimated cost of therapy per year of life saved would be $13,000 in low-risk patients, $3,600 in medium-risk patients, and $2,400 in high-risk patients. As compared with coronary-artery bypass grafting and the medical treatment of hypertension, routine beta-adrenergic-antagonist therapy has a relatively favorable cost-effectiveness ratio. PMID- 2898731 TI - Complexity of the early genetic response to growth factors in mouse fibroblasts. AB - Genes whose expression is growth factor regulated are likely to be important components in the mechanisms controlling cell proliferation and differentiation. With the aim of identifying some of those genes, a lambda cDNA library was prepared with poly(A)+ RNA from quiescent NIH 3T3 cells stimulated with serum for 4 h in the presence of cycloheximide. Differential screening of approximately 200,000 recombinant phage plaques revealed 2,540 clones that cross hybridized preferentially with [32P]cDNA derived from RNA of stimulated cells rather than with cDNA derived from nonstimulated cells. Cross hybridization of these clones identified 82 independent sequences, including c-fos and c-myc. Seventy-one clones were further studied. Analysis of the changes in transcription and mRNA levels after serum stimulation demonstrated that the kinetics and extent of the induction vary dramatically between the different genes. Cycloheximide in all cases superinduced the mRNA levels by two mechanisms, inhibiting the shutoff of transcription and prolonging the half-lives of the mRNAs. Our results showed that induction of proliferation is accompanied by the onset of a complex genetic program. PMID- 2898730 TI - Infrequent genomic rearrangement and normal expression of the putative RB1 gene in retinoblastoma tumors. AB - Retinoblastoma (RB) tumors develop when both alleles of a gene (RB1) are mutated and unable to function normally. Recently, Friend et al. [S. H. Friend, R. Bernards, S. Rogelj, R. A. Weinberg, J. M. Rapaport, D. M. Albert, and T. P. Dryja, Nature (London) 32:643-646, 1986] reported the cloning of a gene, 4.7R, with some properties expected for the RB1 gene, namely, a high frequency (30%) of genomic rearrangements in tumors and absence of message in all RB tumors examined. To extend the characterization of this gene, we used 4.7R probes to search for genomic rearrangements of DNA and to study the expression of the 4.7R gene in RB tumors, osteosarcoma (OS) tumors arising in RB patients, and other normal and malignant tissues. In 34 previously unreported RB and OS tumors arising in RB patients, we observed only four (12%) with genomic abnormalities. Transcripts of 4.7R were present in 12 of 17 RB tumors, 2 of 2 OS tumors, and all non-RB tumors and normal tissues tested. We were unable to confirm the high frequency of truncated messages of 4.7R in RB tumors reported by Lee et al. (W. H. Lee, R. Bookstein, F. Hong, L. J. Young, J. Y. Shaw, and E. Y. Lee, Science 235:1394-1399, 1987) and Fung et al. (Y. K. Fung, A. L. Murphree, A. Tang, J. Qian, S. H. Hinrichs, and W. F. Benedict, Science 236:1657-1661, 1987) but did confirm the presence of a truncated transcript in the RB cell line Y79. Of the RB and RB-related OS tumors which appeared normal on Southern blots, 2 of 26 or 12% had abnormal transcripts, giving a combined frequency of 22% abnormalities in the 4.7R gene detectable by Southern and Northern (RNA) blot analyses. PMID- 2898734 TI - Neuronal development. Not all about eve. PMID- 2898735 TI - Pattern formation in the developing eye of Drosophila melanogaster is regulated by the homoeo-box gene, rough. AB - Homoeo-box genes play a central role in the regulation of embryogenesis in Drosophila melanogaster. Their widespread phylogenetic distribution, and the tissue and stage specificity of their expression in other organisms, argue that they play a general and significant role in animal development. In D. melanogaster, all homoeo-box genes characterized to date are involved in major aspects of embryogenesis. We report here the molecular characterization of a Drosophila homoeo-box gene that has no apparent involvement in early embryogenesis. The gene appears to be rough, a gene implicated in pattern formation in the developing eye. It is expressed in cells within, and posterior to, the morphogenetic furrow, the site of the primary pattern forming events in the developing retina, and also in a region of the brain of the third instar larva. We have found no genetic or molecular evidence of a role for this gene in other aspects of fly development. PMID- 2898737 TI - [Treatment of severe alcoholic delirium]. PMID- 2898736 TI - [Season-related forms of depression. II. Modification by phototherapy and biological results]. AB - The efficacy of phototherapy with bright, fluorescent, full-spectrum light for treatment of seasonal affective disorders (SAD) has now been widely demonstrated in controlled studies. However, treatment with dim light did not reveal a significant therapeutic improvement. Specific parameters of light treatment are necessary or optimal for producing this response and light intensity and duration in contrast to timing and spectrum seem to be a major importance. The mechanism of action of phototherapy is closely linked to the psychobiology of SAD and has not yet been satisfactorily explained. Among the several theories which have been proposed, the melatonin hypothesis and phase shift hypothesis have been the basis for the earlier studies. Newer theories also include the function of further neuroendocrine systems, as well as neurotransmitter and immune function and electrophysiological mechanisms. Until now, the value of phototherapy in the treatment of other non-seasonal syndromes has not yet been explored thoroughly and this line of research seems worth continuing. PMID- 2898739 TI - Regional distribution of immunoreactive dynorphin A in the human gastrointestinal tract. AB - Immunoreactive dynorphin A (ir-Dyn A) was detected throughout the human gastrointestinal tract by a validated radioimmunoassay. Moreover, the stability of 125I-Dyn A during extraction procedures was confirmed by high performance liquid chromatography. Levels of ir-Dyn A were higher in the stomach and in the small bowel. In tissue samples separated into the main layers composing the gut wall (muscularis externa, submucosa and mucosa) ir-Dyn A was uniformly distributed. An exception was the colon, where concentrations were higher in the muscular portion. Gel permeation chromatography on samples of mucosa and muscularis externa extracts of ileum and gastric fundus, showed immunoreactive material eluting in several forms of apparently higher molecular weight than Dyn A, while only a minor peak was found to coelute with authentic Dyn A. PMID- 2898740 TI - Basic trends in research into the neurochemical mechanisms of learning and memory. PMID- 2898738 TI - Effects of fasting and diabetes on some enzymes and transport of glutamate in cortex slices or synaptosomes from rat brain. AB - Phosphate-activated glutaminase (PAG) and glutamic acid decarboxylase (GAD) were assayed in homogenates and synaptosomes obtained from starved (48 hr or 120 hr) and diabetic (streptozotocin) rat brain cortex. Glutamine synthetase (GS) was assayed in homogenates, microsomal and soluble fractions, from brain cortex of similarly treated rats. L-Glutamate uptake and exit rates were determined in cortex slices and synaptosomes under the same conditions. The specific activity (s.a.) of PAG, a glutamate producing enzyme, decreased (50%) in the homogenate after 120-hr starvation. In synaptosomes it decreased (25%) only after 48-hr starvation. The s.a. of GAD and GS, which are glutamate-consuming enzymes, were progressively increased with time of starvation, reaching 39% and 55% respectively after 120 hr. GS in the microsomes or the soluble fraction and GAD in the synaptosomes showed no change in s.a. under these conditions. Diabetes increased (40%) microsomal GS s.a. and decreased GAD s.a. (18%) in the homogenate. The L-glutamate uptake rate was decreased (48%) by diabetes in slices but no in synaptosomes. It is suggested that a) enzymes of the glutamate system respond differently in different subcellular fractions towards diabetes or deprivation of food and b) diabetes may affect the uptake system in glial cells but not in neurons. PMID- 2898742 TI - Effect of a hydrocolloid dressing on the pain level from abrasions on the feet during intensive marching. PMID- 2898741 TI - Experimental modeling of cellular mechanisms of some psychopathological syndromes. PMID- 2898743 TI - [Ulcer disease: as seen today]. PMID- 2898744 TI - [Zollinger-Ellison syndrome based on our surgically treated cases]. PMID- 2898745 TI - [Experimental pre-eclampsia: neurohormonal reaction of pregnant rabbits to uteroplacental ischemia]. PMID- 2898746 TI - Somatic DNA variability in human breast carcinoma. AB - Bkm-related probe 2[8], consisting mainly of GATA repeats, detects a hypervariable pattern of restriction fragment length polymorphisms in human DNA which is normally developmentally stable. However, specific somatic DNA variability was found in 53% (7/13) of human breast carcinomas, but not in eight cases of bladder carcinoma, when compared with leukocyte DNAs from the same patient under the same conditions. Certain of the restriction fragments detected carry both GATA-related sequences and sequences related to the M13 vector. Comparison of BstN1 digests of tumour and cognate leukocyte DNA revealed a further variable ethidium-stained restriction fragment class, not recognised by the probe, in 93% of breast and in 63% of bladder carcinomas. PMID- 2898747 TI - [Possible entry of fragments of a bacterial genome into the trophozoite nucleus of the dysentery amoeba]. AB - The use of Folgen-like electron microscopy reaction has revealed particles in the cytoplasm and nucleus of the dysentery amoeba trophozoites which in their size and resistance to acidic hydrolysis and in their affinity for uranilacetate are similar to tightly packed elements of the bacterial genome. On this basis a conclusion was drawn that some fragments of genomes of phagocytic bacteria can be preserved in the amoebal cell. The community of microorganisms consisting of trophozoites of the dysentery amoeba and bacteria of the intestinal flora is supposed to be a suitable model for studying the possibility of penetration of transgenetic elements from procaryote to eucaryote. PMID- 2898748 TI - The relationship between stimulant medication and tics. AB - Clinical evidence supports the observation that stimulant drugs increase the severity of tics in 25% to 50% of patients with TS, and occasionally can precipitate TS in a patient who did not previously manifest symptoms of this disorder. As ADD is frequently associated with TS, the clinician is often faced with a dilemma. A conservative approach to the use of stimulant medication, stringent criteria for its use, adequate counseling of the child and parents, and a thorough cost-benefit analysis before initiating treatment are required. Behavior management and environmental manipulation can be useful techniques with the child with ADD, and should be tried before medication is considered. PMID- 2898750 TI - [HTLV-I virus and associated chronic neuromyelopathies. Current data and hypotheses]. AB - Human T cell leukemia/lymphoma virus type I (HTLV-I) isolated in 1980, is a human retrovirus. This CD4+ lymphotropic type C retrovirus is endemic in South Western Japan, the Caribbean region and Africa where it is associated with a rare form of lymphoproliferative disease, adult T cell leukemia. Recently, HTLV-I antibodies has been found in sera and CSF from patients with tropical spastic paraparesis (TSP), a chronic neuromyelopathy of unknown etiology common in tropical areas and in Japanese patients with a similar clinical myelopathy. These data suggest that HTLV-I or an antigenically related virus might be neurotropic or neurovirulent and etiologically linked to such chronic neuromyelopathies. The fact that TSP affects about 10 to 100 persons/100,000 in tropical HTLV-I endemic areas, a prevalence comparable to that of multiple sclerosis in temperate regions, increases considerably the public health interest in HTLV-I and associated diseases. The possible neurotropism or neurovirulence of this retrovirus is discussed. PMID- 2898749 TI - Gamma glutamyltransferase contribution to renal ammoniagenesis in vivo. AB - The role of gamma-glutamyltransferase (gamma-GT) in renal ammoniagenesis and glutamine utilization was evaluated in the intact functioning rat kidney. Total NH4+ released, as the sum of renal venous and urinary NH4+, was measured under conditions of chronic metabolic acidosis and paraminohippurate infusion. Ammonia derived from extracellular gamma-GT hydrolysis of glutamine was differentiated from that produced by intracellular phosphate dependent glutaminase (PDG) by employing acivicin, a gamma-GT inhibitor. In non-acidotic animals acivicin administration inhibited gamma-GT 95% and renal venous NH4+ release 48%; NH4+ release into the urine was not inhibited. Chronic metabolic acidosis elevated total NH4+ release 2.5fold, associated with adaptive increase in both gamma-GT and PDG; acivicin reduced total NH4+ released 36% with both renal venous and urinary release effected. The contribution of gamma-GT to total NH4+ production doubles in metabolic acidosis in agreement with the adaptive rise in the in vitro assayed gamma-GT activity. Luminal ammoniagenesis increases in chronic acidosis associated with a fall in urinary glutamine concentration and a rise in the blood to urine glutamine concentration gradient; gamma-GT inhibition eliminates this gradient suggesting luminal ammoniagenesis is largely dependent upon the paracellular glutamine flux. In support of this, paraminohippurate (PAH) infusion increased total renal NH4+ release due entirely to enhanced NH4+ excretion. PAH stimulated luminal ammoniagenesis was associated with an acceleration of renal glutamine extraction and a steeper blood to urine glutamine diffusion gradient; acivicin blocked this response consistent with PAH secretion coupled to activation of intraluminal gamma-GT and glutamine hydrolysis. PMID- 2898751 TI - [Genetic polymorphism and susceptibility to cancer]. AB - Proto-oncogenes, which have been widely implicated in the pathogenesis of malignant human tumors, frequently demonstrate restriction fragment length polymorphism (RFLP). Population studies of such restriction alleles is of potential interest for genetic analysis of cancer susceptibility. Some of the initial date of Krontiris et al (1985) showing a significant increase of rare c ha-ras-l alleles in individuals with tumors, have been confirmed in certain types of cancer (breast cancer, lung adenocarcinoma), whereas others have been refuted (myelodysplasia, melanoma, colon adenocarcinoma). Other significant associations have been found between other proto-oncogene RLFPs and tumors (c-mos and breast cancer, c-raf and non Hodgkins lymphoma, L-myc and lung carcinoma metastasis). Although they are controversial, these studies should be extended, in order to determine whether the presence of certain alleles is a contributing factor in the development of certain tumors. PMID- 2898752 TI - [Autografts of blood cells at various stages]. AB - Thirty-nine patients with acute myeloblastic or lymphoblastic leukaemia had peripheral blood mononuclear cells collected by 3 continuous-flow leukapheresis as they entered first remission after induction chemotherapy. CFU-GM were assayed as a measure of the number of haemopoietic stem cells in each collection. Numbers of CFU-GM harvested varied among the patients (for example 0.27 to 155.10(4)/kg for ANLL patients). Nineteen patients underwent peripheral blood stem cells autografts after a conditioning regimen with high dose cyclophosphamide and TBI. The patients were transfused with a median of 2.2.10(4)/kg CFU-GM cells (0.28 to 100.10(4) CFU-GM/kg). Only 1 patient had a graft failure. The rate of haemopoietic recovery was studied for our patients and those reported in the literature. A strong correlation exists between the numbers of CFU-GM transfused and the rate of granulocytes and platelets recovery. Very rapid recovery are regularly obtained when the number of CFU-GM transfused is superior to 5.10(4)/kg. PMID- 2898753 TI - [Adult T-cell leukemia associated with HTLV1 and positive HIV2 serology in an African woman]. AB - We report a case of acute adult T-cell leukemia associated with HTLV1 infection in a young African woman. The leukemic proliferation consisted of CD4-, CD25 positive lymphoid cells with typically convoluted nuclei and monoclonal integration of the HTLV1-proviral DNA. The clinical course was characterized by a rapid progression of the leukemia with development of hypercalcemia, resistance to chemotherapy, and the presence of multiple opportunistic infections. The additional finding of a seropositivity for HIV2 raises the problem of the respective contribution of the two retroviruses in this patient's disease. PMID- 2898756 TI - Isolation and mapping of a polymorphic DNA sequence (pTHH22) on chromosome 9 [D9S12]. PMID- 2898755 TI - Complete cDNA sequence coding for the human T cell receptor alpha chain HPB-ALL. PMID- 2898757 TI - Isolation and mapping of a polymorphic DNA sequence (pHHH157) on chromosome 6p [D6S29]. PMID- 2898754 TI - Trans-activation of transcription, from promoters containing immunoglobulin gene octamer sequences, by myeloma cell mRNA in Xenopus oocytes. AB - To study factors required for immunoglobulin gene transcription hybrid promoters were made by linking octamer elements to a Xenopus albumin gene construct containing only 50bp of the albumin gene promoter. When injected into oocytes these hybrid promoters directed transcription far less efficiently than the unmodified 50bp albumin gene promoter fragment. Activity of the hybrid promoter, but not the unmodified albumin promoter, could be stimulated by preinjection of poly(A)+ RNA from NS1 myeloma cells. This stimulation may be caused by translation of the NS1 poly(A)+ RNA into transcription factors that act on the octamer. Both the reduction in transcription caused by octamer insertion and the extent of the inducibility by NS1 RNA are greater when two, rather than one, octamers are inserted. PMID- 2898758 TI - Isolation and mapping of a polymorphic DNA sequence (pHHH106) on chromosome 1 [D1S67]. PMID- 2898759 TI - Isolation and mapping of a polymorphic DNA sequence (pCMI40) on chromosome 13 [D13S49]. PMID- 2898760 TI - Isolation and mapping of a polymorphic DNA sequence (pCMM62) on chromosome 14 [D14S21]. PMID- 2898762 TI - Isolation and mapping of a polymorphic DNA sequence (pCMM6) on chromosome 20 [D20S19]. PMID- 2898761 TI - Isolation and mapping of a polymorphic DNA sequence (pEFZ31) on chromosome 22 [D22S32]. PMID- 2898763 TI - Isolation and mapping of a polymorphic DNA sequence (pCMM86) on chromosome 17q [D17S74]. PMID- 2898764 TI - RFLP for the human erb-A beta locus. PMID- 2898765 TI - An RFLP in the gene for the human pro-alpha 2 chain of type V collagen (COL5A2). PMID- 2898766 TI - SnR30: a new, essential small nuclear RNA from Saccharomyces cerevisiae. AB - The gene for a previously unidentified small nuclear RNA has been cloned from Saccharomyces cerevisiae and its nucleotide sequence has been determined. The RNA, snR30, was mapped to a unique coding sequence 605 nucleotides long. SnR30 appears to be one of the most abundant snRNAs of S, cerevisiae in that it can be resolved by ethidium bromide staining on one-dimensional denaturing gels of total yeast RNA. Like other snRNAs, snR30 is enriched in nuclei preparations and possesses a trimethyl guanosine cap structure at its 5' end. After substituting one allele of the wild type gene in a diploid strain for a deleted gene, after sporulation, haploid strains carrying the deletion were unable to grow, indicating that snR30 is required for an essential, but as yet, unknown function. The nucleotide sequence close to the initiation site of the SNR30 gene is similar to that of other yeast SNR genes whose transcripts are associated with pre-rRNA, suggesting that snR30 is related to this group of snRNAs. PMID- 2898767 TI - Components required for in vitro cleavage and polyadenylation of eukaryotic mRNA. AB - We have studied in vitro cleavage/polyadenylation of precursor RNA containing herpes simplex virus type 2 poly A site sequences and have analyzed four RNA/protein complexes which form during in vitro reactions. Two complexes, A and B, form extremely rapidly and are then progressively replaced by a third complex, C which is produced following cleavage and polyadenylation of precursor RNA. Substitution of ATP with cordycepin triphosphate prevents polyadenylation and the formation of complex C however a fourth complex, D results which contains cleaved RNA. A precursor RNA lacking GU-rich downstream sequences required for efficient cleavage/polyadenylation fails to form complex B and produces a markedly reduced amount of complex A. As these GU-rich sequences are required for efficient cleavage, this establishes a relationship between complex B formation and cleavage/polyadenylation of precursor RNA in vitro. The components required for in vitro RNA processing have been separated by fractionation of the nuclear extract on Q-Sepharose and Biorex 70 columns. A Q-Sepharose fraction forms complex B but does not process RNA. Addition of a Biorex 70 fraction restores cleavage activity at the poly A site but this fraction does not appear to contribute to complex formation. Moreover, in the absence of polyethylene glycol, precursor RNA is not cleaved and polyadenylated, however, complexes A and B readily form. Thus, while complex B is necessary for in vitro cleavage and polyadenylation, it may not contain all the components required for this processing. PMID- 2898769 TI - A new Sst 1 RFLP associated with human insulin receptor locus. PMID- 2898768 TI - At least three human homeoboxes on chromosome 12 belong to the same transcription unit. AB - Mammalian homeoboxes show a clustered chromosomal organization. In the mouse, at least seven homeoboxes on chromosome 6 and at least six on chromosome 11 identify the murine Hox-1 and Hox-2 loci, respectively. A number of homeoboxes on chromosome 7 define the human HOX-1 locus and homeoboxes on chromosome 17 define the human HOX-2 locus. We studied the genomic organization of three homeobox sequences of the HOX-3 locus on chromosome 12 and analyzed transcripts from this region. Structural characterization and sequencing of several cDNA clones reveal that the three homeobox sequences present in this chromosomal region identify a single transcription unit. Primary transcripts are alternatively processed to give mature messengers with a common 5' noncoding exon encoding different proteins containing one of the three homeodomains. PMID- 2898770 TI - Isolation and mapping of a polymorphic DNA sequence (pTHIZ53) on chromosome 12 [D12S18]. PMID- 2898771 TI - Isolation and mapping of a polymorphic DNA sequence (pYNZ15) on chromosome 2 [D2S50]. PMID- 2898772 TI - Isolation and mapping of a polymorphic DNA sequence (pMHZ13) on chromosome 9q [D9S13]. PMID- 2898773 TI - Isolation and mapping of a polymorphic DNA sequence (pYNH3) on chromosome X [DXS287]. PMID- 2898774 TI - [DNA restriction fragment length polymorphism (RFLP) of insulin and apolipoprotein A-I (apo A-I) genes in patients with diabetes mellitus coexistent with polyendocrinopathy]. PMID- 2898775 TI - Pancreatic endocrine tumors. AB - In this review the current state of our understanding of endocrine tumors of the pancreas is considered. It is based on the experience with a series of 365 tumors. The first part of the article focuses on origin and classification, markers, frequency, criteria of malignancy as well as general structural features of the pancreatic endocrine tumors. In the second half of the article the functioning tumors, i.e. tumors that cause hormonal syndromes, and the nonfunctioning tumors as well as the endocrine tumors associated with multiple endocrine neoplasia type 1 are dealt with in detail. Special emphasis is put on the immunocytochemical profile and the biological features of the respective tumors. PMID- 2898777 TI - [Drug-induced lithiasis of the choledochus]. PMID- 2898776 TI - Elevated level of beta-adrenoceptors in intact hepatocytes from partially hepatectomized rats. AB - The binding characteristics of 125I-iodocyanopindolol (125I-ICYP) and 3H-CGP 12177 to intact hepatocytes and a particulate fraction prepared from hepatocytes from sham-operated and partially hepatectomized rats were compared. In the particulate fraction, the beta-adrenoceptor number increased 4-10-fold after partial hepatectomy. 125I-ICYP binding to intact cells demonstrated a high fraction of non-specific binding, although phentolamine was included in the assay to reduce non-specific binding. 3H-CGP-12177 binding to intact cells also demonstrated a higher fraction of non-specific binding than in most cell types. In intact cells, the beta-adrenoceptor number increased 5-6-fold after partial hepatectomy. The number of receptors was comparable in intact cells and the broken cell preparation, indicating that receptors are conserved during the preparation of the particulate fraction. PMID- 2898778 TI - The effects of drugs on the formation of Theileria annulata merozoites in vitro. AB - The effects of colchicine, taxol, dinitrophenol, sodium azide, TLA-144, and obioactin on Theileria annulata schizonts were tested in vitro and studied by means of light and electron microscopy. Colchicine (0.001-5 microM) and taxol (1 microM) completely inhibited the mitosis of the host cell. This resulted in higher numbers of schizont nuclei after 96 h, since the division of the parasites was apparently not affected. Increasing numbers of schizont nuclei were also obtained after incubation of parasitized lymphocytes for 7 day at 41 degrees C with a daily medium exchange. PMID- 2898779 TI - Cholecystokinin (CCK)-4 and CCK-8 stimulate islet hormone secretion in vivo in the pig. AB - It is known that cholecystokinin (CCK) stimulates islet hormone secretion under a variety of experimental conditions. Since CCK occurs in several different molecular forms, with 58, 39, 33, 12, 8, or 4 amino acid residues, the question has evolved as to which is the shortest active form of CCK. We therefore investigated the influences of the C-terminal octapeptide of CCK, CCK-8 (sulfated form) and of the C-terminal tetrapeptide, CCK-4, on the secretion of insulin, glucagon, and somatostatin from the pig pancreas in vivo by infusing each of the two peptides into the superior pancreatic artery. We found that islet hormone secretion increased promptly upon infusion of both CCK-8 and CCK-4. Thus, the secretion of insulin was stimulated from 51 +/- 12 to 295 +/- 70 microU/min during the first 2 min after injection of CCK-8 and from 40 +/- 12 to 240 +/- 78 microU/min after injection of CCK-4. Similarly, the secretion of glucagon was stimulated from 240 +/- 45 to 357 +/- 38 pg/min after CCK-8 and from 282 +/- 44 to 335 +/- 43 pg/min after CCK-4, and somatostatin secretion was stimulated from 112 +/- 7 to 226 +/- 12 pg/min by CCK-8 and from 105 +/- 11 to 246 +/- 16 pg/min by CCK-4. With regard to the efficiency to stimulate the secretion of these three islet hormones, CCK-8 and CCK-4 were equipotent. We conclude that in pigs, CCK-8 and CCK-4 both stimulate the secretion of insulin, glucagon, and somatostatin from the pancreas in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898780 TI - In vitro expression in eukaryotic cells of a prion protein gene cloned from scrapie-infected mouse brain. AB - It has been proposed that the causative agent of scrapie represents a class of infectious particle that is devoid of nucleic acid and that an altered form of the endogenous prion protein (PrP) is the agent. However, it has been difficult to exclude the possibility that PrP purified from scrapie tissues might be contaminated with a more conventional viral agent. To obtain PrP uncontaminated by scrapie-infected tissues, PrP cDNA cloned from a scrapie-infected mouse brain was expressed in mouse C127 cells in vitro. mRNA and protein encoded by the cloned PrP gene were identified. The expressed PrP polypeptides appeared to be glycosylated and were released from the cell surface into the medium. Homogenates of the cells expressing the cloned PrP gene were inoculated into susceptible mice but failed to induce clinical signs of scrapie. Thus, either PrP is not the transmissible agent of scrapie or the expressed PrP requires additional modification to be infectious. PMID- 2898783 TI - Lack of evidence for association of meiotic nondisjunction with particular DNA haplotypes on chromosome 21. AB - The hypothesis of a predisposition to meiotic nondisjunction for chromosome 21 carrying a specific molecular haplotype has been tested. The haplotype in question is defined by the restriction fragment length polymorphisms for the D21S1/D21S11 loci. Our results obtained on a sample of Northern Italian families with the occurrence of trisomy 21 (Down syndrome) failed to support this hypothesis, contradicting a previous study [Antonarakis, S. E., Kittur, S. D., Metaxotou, C., Watkins, P. C. & Patel, A. S. (1985) Proc. Natl. Acad. Sci. USA 82, 3360-3364]. These findings rule out an association between any specific D21S1/D21S11 haplotype (as well as other haplotypes for the D21S13, ETS2, and D21S23 loci) and a putative cis-acting genetic element favoring the meiotic missegregation of chromosome 21. For this reason, no preventive screening for couples at risk for trisomy 21 may be based on any of the haplotypes tested. PMID- 2898782 TI - Hox-5.1 defines a homeobox-containing gene locus on mouse chromosome 2. AB - We have isolated a murine homeobox-containing gene, Hox-5.1, by virtue of its relatedness to the Hox-1.4 gene. In situ hybridization to metaphase spreads mapped Hox-5.1 to band D of mouse chromosome 2. Sequence comparisons indicate that Hox-5.1 is the murine homolog of the human C13 homeobox-containing gene. Hox 5.1 also bears significant similarity to the Xenopus Xhox-1A homeobox-containing gene and the Drosophila deformed homeotic gene at N-terminal and homeobox regions. Hox-5.1 transcripts were detected in mouse embryos, in adult mouse testis, kidney, heart, and intestine, and in mouse embryonal carcinoma cells treated with retinoic acid. In situ hybridization to sections from whole mouse embryos revealed Hox-5.1 expression in spinal cord and prevertebrae. PMID- 2898781 TI - Nuclear posttranscriptional processing of thymidine kinase mRNA at the onset of DNA synthesis. AB - The posttranscriptional regulatory mechanism(s) underlying thymidine kinase (TK) mRNA accumulation was investigated in BALB/c 3T3 cells during their progression from G0 into S phase of the cell cycle. Very little TK mRNA could be detected in either the nuclear or the cytoplasmic compartment from cells harvested in G0 or G1. At the onset of S phase, however, the level of nuclear TK mRNA precursors and mature TK mRNAs increased dramatically. The high molecular weight TK heterogeneous nuclear RNA species detected in the nuclei of S-phase cells were polyadenylylated and hybridized to intron sequences derived from the TK gene. A series of high molecular weight precursors could be chased to lower molecular weight species in the presence of actinomycin D, suggesting an ordered removal of intron sequences with the kinetics of a precursor-product relationship. These results demonstrate a striking change in the nuclear posttranscriptional processing of TK heterogeneous nuclear RNA at the G1-S boundary and, furthermore, define a model system for the examination of RNA-processing events in vivo. PMID- 2898784 TI - Identification of carbohydrate structures that are possible receptors for Neisseria gonorrhoeae. AB - Different strains and isogenic variants of Neisseria gonorrhoeae were assayed for their ability to bind glycolipids extracted from various sources. Among a large number of reference glycolipids, binding was observed only to lactosylceramide [Gal(beta 1-4)Glc(beta 1-1)Cer], isoglobotriaosylceramide [Gal(alpha 1-3)Gal(beta 1-4)Glc(beta 1-1)Cer], gangliotriaosylceramide [GalNAc(beta 1-4)Gal(beta 1 4)Glc(beta 1-1)Cer], and gangliotetraosylceramide [Gal(beta 1-3)GalNAc(beta 1 4)Gal(beta 1-4)Glc(beta 1-1)Cer]. The latter two glycolipids bound gonococci with the highest affinity. Lactosylceramide and gangliotriaosylceramide were found in glycolipid preparations from ME180 cells, an epithelial cell line derived from a human cervical carcinoma, and thus are possible receptors for gonococci. The gonococcal surface component that bound the above glycolipids is a protein distinct from pilin and protein II. PMID- 2898785 TI - Requirement of GTP on somatostatin-induced K+ current in human pituitary tumor cells. AB - The role of GTP on somatostatin-induced K+ current increase was examined in dissociated human pituitary tumor cells obtained from three acromegalic patients. Pituitary cells in culture were voltage-clamped by using the patch clamp technique in the whole-cell configuration. Somatostatin (100 nM) increased the membrane permeability to K+ ions and inhibited hormone secretion. A current voltage relation of the somatostatin-induced K+ current showed an inward rectification when the concentration of extracellular K+ ions was increased. The amplitude of the somatostatin-induced K+ current decreased during recording when the patch pipette solution did not contain GTP; addition of 100 microM GTP to the patch pipette solution prevented this reduction. Intracellular application of 100 microM guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S] evoked an inward rectifying K+ conductance in the absence of somatostatin. After the GTP[gamma S] induced K+ conductance reached a steady level, application of somatostatin did not further increase the K+ conductance. In pertussis toxin-treated cells GTP[gamma S] did not evoke K+ conductance. It was concluded that somatostatin induced K+ channels were regulated by a GTP-binding protein. PMID- 2898787 TI - Neuropeptide Y as an autonomic neurotransmitter. PMID- 2898786 TI - Expression of receptors for cholecystokinin and other Ca2+-mobilizing hormones in Xenopus oocytes. AB - The expression of receptors for cholecystokinin (CCK) and other similar acting Ca2+-mobilizing hormones was studied in Xenopus laevis oocytes. Poly(A)+ RNA was prepared from pancreatic AR42J cells, which normally express receptors for CCK and bombesin and the RNA injected into oocytes. The presence of these pancreatic receptors on the oocytes was then demonstrated by hormone-induced mobilization of 45Ca2+. CCK receptors were present 1 day (maximum, 2 days) after injection of RNA and were generally proportional to the amount of poly(A)+ RNA injected (1-50 ng). Oocyte CCK receptors retained selectivity for CCK analogs (CCK8 greater than unsulfated CCK8 greater than CCK4) and were blocked by the specific CCK receptor antagonist CR 1409. When poly(A)+ RNA was subjected to size fractionation on sucrose gradients, activity-inducing CCK receptors showed a single peak centered at 3 kilobases. The generality of this oocyte system for expressing Ca2+ mobilizing hormone receptors was further shown by expression of a response to bombesin after injection of AR42J cell RNA and a response to vasopressin and angiotensin II when poly(A)+ RNA from rat liver was injected. No response to CCK was demonstrable after injection of liver RNA, demonstrating the specificity of this assay. PMID- 2898788 TI - [Treatment of attention deficit disorders in adulthood using psychostimulants and low-dose neuroleptics--a critical case report]. AB - Psychiatric research and therapy recently evinced increasing interest in patients suffering from attention deficit disorder. "Attention deficit disorder" is a category of mental disorders listed in DSM III, with a separate diagnostic subgroup for attention deficit disorders persisting in adults who had been hyperkinetic in childhood ("attention deficit disorder-residual type"); however, this does not feature in a corresponding manner in the ICD 9 version. Since there are practically no therapy studies in existence within the ICD range that can be relevant for such disorders, we studied the treatment of an adult patient with the psychostimulant fenetylline under clinical conditions and found a significant improvement in attention performance. However, on integration in a long-term day clinic rehabilitation programme we found that low-dose neuroleptic treatment was on the whole of greater benefit than fenetylline treatment. PMID- 2898789 TI - The mode of action of bromocriptine following pretreatment with reserpine and alpha-methyl-p-tyrosine in rats. AB - The ability of bromocriptine (BRC), a selective dopamine D-2 receptor agonist, to induce yawning responses was studied in rats pretreated with reserpine and alpha methyl-p-tyrosine (alpha-MPT). BRC (1 20 mg/kg IP) evoked yawning responses, which were pronounced at 2.5 mg/kg and characterized by the head moving downward. Higher doses of BRC (5 20 mg/kg) dose-dependently delayed the onset and peak time of yawning. A low dose of the selective D-1 dopamine receptor agonist SK&F38393 did not induce yawning but enhanced the BRC-induced response. Pretreatment with reserpine (1 and 5 mg/kg SC), alpha-MPT (100 and 300 mg/kg IP) and reserpine (1 mg/kg) plus alpha-MPT (100 mg/kg) was able to significantly reduce BRC-induced yawning. The inhibitory effects were prevented by a low dose of SK&F38393 (0.5 mg/kg IP). In particular, combined treatment with reserpine (5 mg/kg) and BRC (10 and 20 mg/kg) elicited upright fighting and jumping behaviors which were inhibited by haloperidol (1 mg/kg IP), a non-selective D-1 and D-2 receptor antagonist, SCH23390 (0.05 mg/kg SC). a selective D-1 receptor antagonist, or sulpiride (20 mg/kg IP), a potent D-2 receptor antagonist, and were potentiated by SK&F38393 (0.5 mg/kg). SCH23390 (0.05 mg/kg) decreased BRC-induced yawning and the apomorphine (low doses)-induced potentiation of BRC yawning, and prevented the apomorphine (high doses)-induced reduction of BRC yawning. SCH23390 also inhibited apomorphine-induced stereotypy and BRC-induced potentiation of apomorphine stereotypy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898790 TI - The threshold lowering effects of MDMA (ecstasy) on brain-stimulation reward. AB - 3,4-Methylenedioxymethamphetamine (MDMA) is a psychoactive phenylisopropylamine which is structurally similar to both amphetamine-related sympathomimetics and the hallucinogen, mescaline. MDMA produces pleasurable effects which include euphoria, and recent reports continue to demonstrate its widespread recreational use. The aim of the present study was to assess the effects of racemic MDMA on the threshold for rewarding intracranial self-stimulation, an animal model used to assess a drug's abuse liability in man. Rewarding electrical stimulation was delivered via electrodes stereotaxically implanted in the medial forebrain bundle lateral hypothalamic area of the rat brain. Thresholds were determined by means of a rate-independent psychophysical method. MDMA produced a dose-related lowering of the reward threshold in all four animals tested. Given that increased sensitivity for rewarding brain stimulation, measured as a lowering of the reward threshold, is an animal model of drug-induced euphoria these results suggest a similar mode of action for its reinforcing effects as other abused substances. PMID- 2898792 TI - Clinical profile of gepirone, a nonbenzodiazepine anxiolytic. PMID- 2898791 TI - Drug discrimination studies with MDMA and amphetamine. AB - The term entactogen has recently been introduced to describe a new pharmacological class of compounds best represented by 3,4 methylenedioxymethamphetamine, MDMA, and its alpha-ethyl homologue MBDB. The present study was designed to test the similarities of the discriminative stimulus properties produced by MDMA and MBDB, as well as to elaborate further the distinction between entactogens, hallucinogens and stimulants. Two groups of rats were trained to discriminate saline from either racemic MDMA hydrochloride (1.75 mg/kg) or S-(+)-amphetamine sulfate (1.0 mg/kg) in a two-lever drug discrimination task. The (+/-)-MDMA cue completely generalized to S-(+)-MDMA, S (+)-amphetamine, (+/-)-MDA, S-(+)-MBDB, (+/-)-MBDB, R-(-)-MDMA, and R-(-)-MBDB, but not to LSD or DOM. The S-(+)-amphetamine cue generalized to (+/-) methamphetamine, but not to racemic MDMA or MBDB, nor to their optical isomers. The S-(+)-isomers of both MDMA and MBDB were more potent than the R-(-)-isomers. The results indicate that MDMA and MBDB may share a component of their discriminative stimulus properties which is different from both stimulants and hallucinogens. Although MDA and MDMA have been shown to be amphetamine-like, the lack of stimulant effects for MBDB suggests that amphetamine-like stimulant activity is not necessary for a compound to share discriminative stimulus properties with MDMA. PMID- 2898793 TI - Pilot study of alpidem, a novel imidazopyridine compound, in anxiety. PMID- 2898794 TI - A 5-HT1A ligand with both antidepressant and anxiolytic properties. PMID- 2898795 TI - Neuroleptic treatment and prediction of response. PMID- 2898796 TI - Kraepelinian schizophrenia: a subgroup of schizophrenia? PMID- 2898797 TI - Stimulant treatment for adolescents with attention deficit disorder. PMID- 2898798 TI - [Electron microscopy of damaged solder]. PMID- 2898799 TI - Effects of antidepressants on monoamine transporters. AB - 1. Using [3H]antidepressants, high affinity binding sites associated with the neuronal transporter for serotonin, noradrenaline, dopamine and adrenaline have been identified. 2. The association of high affinity [3H]imipramine binding with the serotonin transporter in brain and platelets is well established. Although the exact relationship between the [3H]imipramine recognition site and the serotonin transporter remains to be elucidated, it appears that the [3H]imipramine labelled component of the serotonin transporter represents a novel receptor that functions to modulate serotonin uptake. 3. Most data available to date support the hypothesis that [3H]imipramine binding to platelet represents a biological marker in depression. The majority of studies indicate that the Bmax of platelet [3H]imipramine binding is lower in depressed, untreated patients than in the control population and that this finding is relatively specific to depression. 4. Among the [3H]antidepressant binding sites associated with the other monoaminergic transporters, the recent identification of [3H]desipramine binding to the neuronal transporter for adrenaline offers novel perspectives. Thus, given the high affinity for [3H]desipramine binding to the adrenaline transporter in the frog heart for not only desipramine but also imipramine and the atypical antidepressants mianserin and iprindol, it is possible that an interaction with the adrenaline transporter is of significance to the clinical effects of antidepressant drugs. PMID- 2898800 TI - [Reactions to withdrawal of benzodiazepines: implications for the practitioner]. PMID- 2898801 TI - [Springtime rhinoconjunctivitis: current findings]. PMID- 2898802 TI - [The status, objectives and prospects of rheumatological services in the RSFSR in the light of the resolutions of the 27th Congress of the CPSU]. PMID- 2898803 TI - [Study of the effect of DDT analogs on the activity of selected enzymes in rats in an acute experiment]. PMID- 2898804 TI - [Genetics of type 1 diabetes: study of the polymorphism of DNA restriction fragments]. PMID- 2898805 TI - Biologically ineffective gonadotropin secretion: two cases. AB - Symptoms of gonadal insufficiency, in the presence of high serum levels of gonadotropins, generally indicate primary gonadal failure. An exception to this generalization is the secretion of ineffective gonadotropic hormone secretion by the pituitary. One such case was reported in 1979. However rare it may be, this disorder should still be taken into consideration when evaluating hypogonadal patients. In fact, it may not be so rare as it is supposed. In this report, two such cases are presented. They both show signs of gonadal insufficiency in the presence of high serum gonadotropin concentrations, but responding normally to exogenously administered chorionic gonadotropin. PMID- 2898806 TI - Sulfasalazine and 5-aminosalicylic acid inhibit contractile leukotriene formation. AB - Sulfasalazine, used therapeutically in the treatment of ulcerative colitis, is cleaved in vivo to form 5-aminosalicylic acid (5-ASA) and sulfapyridine. In an isolated preparation of rat peritoneal cells both sulfasalazine (IC50 = 0.15 mM) and 5-ASA (IC50 = 2.3 mM), but not sulfapyridine, inhibited calcium ionophore stimulated formation of contractile leukotriene activity. This activity, although not identified directly, is attributable to a mixture of leukotriene C4 and leukotriene D4 (commonly referred to as SRS-A, or slow-reacting substance of anaphylaxis). Reference compounds evinced expected activities (IC50 = 0.024 mM for phenidone, IC50 = 0.3 microM for nordihydroguaiaretic acid, IC50 = 0.033 mM for BW 755C), whereas para-aminosalicylic acid and thiosalicylic acid were inactive. These properties of sulfasalazine may contribute to its therapeutic efficacy in vivo. PMID- 2898807 TI - Sulphasalazine in the treatment of reactive arthritis. PMID- 2898808 TI - A two year prospective study of rearrests for drunken driving. AB - 393 drunken drivers, arrested within a six-month period in 1984/85, were selected for a prospective study of rearrests for drunken driving. Within the following two years, 119 (30%) of the drivers were rearrested. They were responsible for 232 detected drunken driving offences. The rearrest rate increased with increasing blood alcohol concentration (measured at the time of selection). The rearrest rate was greater for those with elevated blood gamma glutamyltransferase (a marker of excessive alcohol consumption), and was markedly greater for those with more than one arrest for drunken driving preceding the observation period. PMID- 2898809 TI - [Drug treatment of chronic inflammatory diseases of the intestine]. PMID- 2898810 TI - Purification and characterization of mouse hematopoietic stem cells. AB - Mouse bone marrow hematopoietic stem cells were isolated with the use of a variety of phenotypic markers. These cells can proliferate and differentiate with approximately unit efficiency into myelomonocytic cells, B cells, or T cells. Thirty of these cells are sufficient to save 50 percent of lethally irradiated mice, and to reconstitute all blood cell types in the survivors. PMID- 2898811 TI - [Mutual potentiation of the analgesic effects of [MET5] enkephalin, dynorphin A (1-13) and morphine in the spinal cord of the rat]. PMID- 2898812 TI - [Effect of starvation on the secretion of insulin and its mechanism in rats]. PMID- 2898813 TI - Pharmacological control of gastric acid secretion. PMID- 2898814 TI - [Attack on education meets with increased activities]. PMID- 2898815 TI - [Mass of paper dominates students meeting in Korsor]. PMID- 2898816 TI - Anticoagulant activity in cell homogenate of adult T cell leukemia. AB - The hemostatic abnormality in 18 patients with adult T cell leukemia (ATL) was studied. Activated partial thromboplastin time (APTT) was slightly prolonged and prekallikrein activity was markedly low in these patients. The leukemic cell homogenate from these patients prolonged the recalcification time (RCT) of normal plasma; homogenates containing more than 3 x 10(3) cells/microliter prolonged it, although a lower cell concentration shortened it. The crude anticoagulant fraction from the gel filtration, with a molecular weight of about 34,000, prolonged RCT. The crude anticoagulant did not affect prothrombin time (PT), thrombin activity or activated X activity at any concentration, but prolonged the contact activation test, inhibited the activation of prekallikrein and prolonged RCT of Fletcher trait, Fitzgerald trait and F XII deficient plasma. These effects of ATL cell homogenate were stronger on platelet poor plasma than on platelet rich plasma. Although ATL cells had low procoagulant activity, increase of leukemic cells made anticoagulant activity predominant, might be the cause of hemostatic abnormality or amplify the bleeding tendency in patients with ATL. PMID- 2898817 TI - Monocytes of patients congenitally deficient in plasma factor XIII lack factor XIII subunit a antigen and transglutaminase activity. AB - Monocytes isolated from patients with severe deficiency in plasma Factor XIII of blood coagulation (FXIII) were tested for FXIII antigen and transglutaminase activity. By immunoperoxidase method the patients' monocytes, in contrast to normal controls, showed no reaction with a monospecific antibody against FXIII subunit a. This result was confirmed by immunoblotting technique, as well. In addition, tissue macrophages tested in one of the patients were also exempt of FXIII subunit a antigen. The transglutaminase activity in FXIII deficient monocytes was below the limit of the detection of the dansylcadaverine incorporation assay. The results suggest that FXIII subunit a of monocytes/macrophages and its plasma and platelet counterparts are closely related or identical proteins and demonstrate that the transglutaminase activity in monocytes is of FXIII origin and tissue transglutaminase is present, if at all, only in insignificant amount. PMID- 2898818 TI - Phospholipase C from clostridium perfringens induces human platelet aggregation in plasma. AB - We studied the aggregating effect of different concentrations of phospholipase C (PLC) (extracted from Clostridium perfringens) on human platelet-rich plasma (PRP). PRP was preincubated with PLC for 3 min at 37 degrees C and the platelet aggregation was followed for 10 min. The threshold aggregating concentration (TAC) of PLC was 3-4 U/ml. We also studied the potentiation of PLC with other stimuli on platelet aggregation. Potentiating stimuli, such as arachidonic acid (AA), ADP. Platelet Activating Factor (PAF) and U-46619 (a stable analogue of cyclic endoperoxides) were all used at subthreshold concentrations. We also studied the possible inhibitory effect of aspirin, apyrase, TMQ, a prostaglandin endoperoxide/thromboxane receptor antagonist and BN-52021, a PAF receptor antagonist. Only aspirin and apyrase were able to reduce aggregation induced by PLC alone and PLC + AA and PLC + ADP respectively. TMQ and BN-52021 were inactive. In ex vivo experiments oral aspirin (500 mg) partially inhibited platelet aggregation induced by PLC alone, PLC + AA and PLC + ADP 2 and 24 h after administration. Aspirin 20 mg for 7 days also reduced aggregation induced by PLC + AA. PMID- 2898819 TI - [Do beta-blockers protect against myocardial infarction?]. PMID- 2898820 TI - [Treatment of anaphylaxis]. PMID- 2898821 TI - [Undescended testes in adulthood. A special case]. PMID- 2898822 TI - [Undescended testes in adulthood. Statistics and tactics]. PMID- 2898823 TI - [Beta agonists]. PMID- 2898824 TI - Use of an in vitro system to study the effects of lead on astrocyte-endothelial cell interactions: a model for studying toxic injury to the blood-brain barrier. AB - We investigated the effect of inorganic lead on the interaction of immature rat astrocytes and bovine adrenal endothelial cells. The two cell types were cultured alone and in coculture in the presence or absence of lead acetate for up to 1 week. A battery of cell specific markers was used for cell identification. Newborn Sprague-Dawley rat brain astrocytes were more sensitive than bovine adrenal endothelial cells to the cytotoxic effects of 10-50 microM lead acetate, as demonstrated by a decrease in cell number and by the presence of intracellular vacuoles and detached cells. The number of astrocytes decreased to 50% of control after 4 days in culture at a concentration of 10 microM lead. In contrast, a mitogenic effect of lead was observed on the endothelial cells at this concentration, with an increase in cell number to 110% of control. In coculture, the two cell types demonstrated a distinctive cellular organization and the astrocytes were less sensitive to the cytotoxic effects of lead than when they were cultured alone. A lead-enhanced induction of a neural capillary enzyme activity, gamma-GTP, was detected histochemically in the coculture system. These results are consistent with a maturing or differentiating effect of the endothelial cells on the astrocytes, making them less susceptible to lead and mature enough to induce gamma-GTP activity in the endothelial cells. PMID- 2898825 TI - [Utilization of the cardio-selective beta receptor blocker Cordanum as premedication in dental-surgical interventions in the ambulatory]. PMID- 2898826 TI - [Atracurium and vecuronium. Advantages and disadvantages]. PMID- 2898827 TI - [Acid secretory function of the kidneys in patients with hemorrhagic fever with the renal syndrome]. PMID- 2898829 TI - Immunoelectron microscopic localization of hepatic transferrin receptors in human liver with and without iron overload. AB - The expression of transferrin receptors (TfR's) has been investigated in eight liver biopsy specimens (four from patients without demonstrable iron and four from patients with iron storage due to primary hemochromatosis (HC)) using immunoelectron microscopy to demonstrate TfR's by the simultaneous application of two specific monoclonal antibodies (OKT9 and B3/25) to tissue chopper sections. In the four specimens without iron overload, hepatocytes, but not sinusoidal lining cells, stained positively and immunoreactivity was mainly localized in the cytoplasm. Positively stained cisternae of the endoplasmic reticulum indicated synthesis of the TfR. The presence of TfR's on segments and coated invaginations of the sinusoidal membrane and in small, but otherwise unidentified vesicles in the cytoplasm is compatible with endo-/exocytotic transport and recycling of TfR's as demonstrated by biochemical studies. Occasional positively stained material in canalicular lumina together with positively stained canalicular microvilli and pericanalicular vesicles suggest that transcellular transport may be an additional pathway for TfR's. In three biopsies showing severe iron overload due to HC, TfR immunoreactivity was completely absent. The remaining specimen showing HC, exhibited relatively mild iron overload and showed only a few positively stained hepatocytes. This supports the previously reported disappearance of hepatic TfR expression in HC when iron overload is severe. PMID- 2898828 TI - Protein degradation in lysosomes from chemically induced malignant rat hepatoma. AB - Hepatocellular carcinomas were induced in rat liver by exposing the animals to diethylnitrosamine and 2-acetylaminofluorene in combination with partial hepatectomy. Light and electron microscopy demonstrated that the general appearance of the tumour tissue was that of highly differentiated malignant hepatocytic cells. Morphometrically there was a difference between normal and malignant cells in that the entire lysosomal apparatus was twice as large in malignant cells as in normal cells. This was mainly due to an increase in the fractional volume of autophagic vacuoles. A total lysosomal fraction (dense bodies and autophagic vacuoles) was isolated and characterized from both control and tumour livers. Marker enzyme analysis showed that the lysosomal enzyme activities were significantly lower in malignant liver tissue. Injection of leupeptin, an inhibitor of cathepsins B, H, and L, into rats did not increase the fractional volume of autophagic vacuoles in tumour tissue as much as in normal liver tissue. The proteolytic rate was lower in the lysosomal fraction from hepatoma cell tissue compared with the lysosomal fraction from normal cell tissue. This could conceivably be due to the lower activities of lysosomal enzymes. However, if the recovery of lysosomes is taken into account no clear-cut difference in lysosomal proteolysis between control and malignant liver tissue was noted. Accordingly, in malignant liver tissue a proteolytic balance is obtained characterized by an increased fractional volume of AVs and lower rate of protein degradation in individual lysosomes. PMID- 2898830 TI - Interdigitating reticulum cells in dermatopathic lymphadenitis: freeze-fracture and ultrathin-section morphology. AB - Dermatopathic lymphadenitis is a non-neoplastic lesion found with various chronic skin lesions and associated with hyperplasia of the thymus-dependent (T) areas. These areas consist chiefly of interdigitating reticulum cells (IDC's), which are known to be accessory cells for T-cell-dependent immune reactions. The most characteristic features of IDC's are the bizarre-shaped cell nucleus, numerous cytoplasmic processes, deep cytoplasmic invaginations, and a close topographical relationship to surrounding (T) lymphocytes. The cytoplasmic processes of IDC's do not interdigitate with adjacent lymphocytes, as previously reported in the literature, but show close interdigitations with the processes of neighboring IDC's. With the freeze-fracture technique it can be seen that IDC's exhibit a characteristic distribution of intramembranous particles (IMP). While, for example, macrophages, epithelioid cells and lymphocytes display a clearly greater number of IMP on the P face than on the E face, IDC's show an equally high particle density on both the P face and the E face. The organelle content of IDC's in dermatopathic lymphadenitis varies considerably. Tubular profiles, the Golgi apparatus and vesicles may be increased in number. Birbeck granules are also found in IDC's, but only rarely. Variations in the numbers of the different cytoplasmic organelles may be a reflection of varying degrees of metabolic activity of IDC's. PMID- 2898831 TI - Unimpaired membrane dynamics in parathyroid cells in insulin deficient rats. AB - The responsiveness of parathyroid cells in insulin deficient and short-term diabetic rats was investigated by morphometric analysis. Insulin deficiency was produced by intravenous injection of D-mannoheptulose and short-term (7 days) diabetes mellitus by intraperitoneal application of streptozotocin. Parathyroid glands were stimulated for parathyroid hormone secretion by decreasing the serum calcium concentration through intravenous infusion of EGTA. Parathyroid cells of controls, insulin deficient, and short-term diabetic rats responded to reduced serum calcium by a 45% increase of the cell surface area. This increase is assumed to be the result of the membrane-bound transport of parathyroid hormone from the Golgi complex and secretory granules to the plasma membrane and subsequent exocytic release of parathyroid hormone induced by the low serum calcium concentration. Therefore, the unimpaired increase in the cell surface area of parathyroid cells in insulin deficient and short-term diabetic rats indicates that insulin does not modulate the release of parathyroid hormone. It is also considered likely that synthesis of parathyroid hormone is not suppressed in short-term diabetes but that fat metabolism is disturbed leading to accumulation of lipid vacuoles. PMID- 2898833 TI - Histogenesis and morphogenesis of epidermoid metaplasia in hamster tracheal organ explant culture. AB - The formation of epidermoid metaplasia was studied in hamster tracheal epithelium in long-term serum-free organ explant culture. Explants were cultured up to 5 weeks in CMRL 1066 with antibiotics and amphotericin B. At 3 weeks there were rare small foci of epidermoid metaplasia and they became larger and more numerous at 4 and 5 weeks. Three dimensional reconstructions from serial sections demonstrated that the small deep-seated foci were discrete and did not reach the epithelial surface, whereas the larger foci were expansive and involved the full thickness of the explant epithelium. Each small focus consisted of a few swollen electron-lucent basal cells attached to the basal lamina, covered by a layer of flattened electron-dense secretory cells which formed a tight-fitting cap over the basal cells. The altered secretory cells displayed moderately well-developed rough endoplasmic reticulum and tonofilament bundles. During the early stages of formation the deep-seated metaplastic foci were completely covered by a layer of normal appearing cuboidal to low-columnar secretory and ciliated cells. Expansion of the metaplastic foci occurred by addition of flattened, electron-dense secretory cells to the cap so that multiple layers of altered secretory cells covered a core of basal cells, analogous to the structure of an onion. The secretory cells became cornified and with time the foci broke through the columnar mucociliary surface layer. In well-advanced foci, the uppermost cornified squames (metaplastic secretory cells) exfoliated into the tracheal lumen. The study emphasizes similarities and differences between the morphogenesis and histogenesis of epidermoid metaplasia in vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898832 TI - Dual secretory and myoepithelial differentiation in the transplantable R3230AC rat mammary carcinoma. AB - The hormone-responsive R3230AC mammary carcinoma, serially transplantable in Fisher rats, shows striking functional and morphological similarities to the normal mammary gland. We have studied its cellular composition by both light and electron microscopy, employing markers of myoepithelial and epithelial cells. We identified two cell types: the major cellular component corresponded to epithelial milk-protein secreting cells, while a second component showed immunocytochemical and ultrastructural characteristics of the myoepithelial cells. These cells were positive with a monoclonal antibody detecting alpha smooth muscle actin. The dual differentiation which normally occurs in breast ducts is therefore reproduced in a malignant experimental tumor. The coexistence of neoplastic cell populations, divergent in morphology and function, that persist in a tumor despite many transplant generations, leads to reconsideration of the relationship between cellular differentiation and malignant transformation. PMID- 2898834 TI - Nuclear growth and chromatin relaxation-condensation cycle in hepatocytes during the proliferative activation of rat liver. AB - In order to quantify the changes in nucleolar and nuclear volumes and in chromatin condensation produced during proliferative activation we have carried out morphometric studies on hepatocyte nuclei during rat liver regeneration using electron microscopy. To minimize the artefactual effects produced by fixation on subcellular structures we have fixed the livers by perfusion with glutaraldehyde. The mean values for the nucleolar and nuclear volumes were progressively increased until 28 h after 66% partial hepatectomy. The maximum values raised for the nuclei and nucleoli at this time were 3 and 4.28 times, respectively, those of controls. Later, nuclear and nucleolar volumes progressively declined. Two waves of diminution in nuclear electron-dense material were produced after hepatectomy. The first occurred between 0 and 12 h, with minimum values 1.34 times lower than those from control animals at 8 h. The second occurred between 12 and 28 h, with minimum values 2.56 times lower than those from control rats at 24 h. These two waves in chromatin relaxation correlate very well with the transcriptional changes described by other authors during the pre-replicative, replicative and mitotic phases of liver regeneration. PMID- 2898836 TI - Polyarteritis nodosa in Jamaicans. PMID- 2898835 TI - [Regulatory effects of terminal products and intermediates of aromatic pathways on rifamycin biosynthesis in Nocardia mediterranei]. PMID- 2898837 TI - A re-examination of the mechanism of ackee-induced vomiting sickness. PMID- 2898838 TI - Electron microscope localization of some enzymes in the blood microvessels supplying the sensory nerve endings. PMID- 2898839 TI - Monoamine-containing islet cells of the pancreas in the pigmented domestic fowl. Fluorescence microscopy and immunohistochemistry. PMID- 2898840 TI - Structure of the ATP-synthase from chloroplasts and mitochondria studied by electron microscopy. AB - The structure of the ATP-synthase, F0F1, from spinach chloroplasts and beef heart mitochondria has been investigated by electron microscopy with negatively stained specimens. The detergent-solubilized ATP-synthase forms string-like structures in which the F0 parts are aggregated. In most cases, the F1 parts are arranged at alternating sides along the string. The F0 part has an approximate cylindrical shape with heights of 8.3 and 8.9 nm and diameters of 6.2 and 6.4 nm for the chloroplast and mitochondrial enzyme, respectively. The F1 parts are disk-like structures with a diameter of about 11.5 nm and a height of about 8.5 nm. The F1 parts are attached to the strings, composed of F0 parts, in most cases, with their smallest dimension parallel to the strings. The stalk connecting F0 and F1 has a length of 3.7 nm and 4.3 nm and a diameter of 2.7 nm and 4.3 nm for the chloroplast and mitochondrial enzyme, respectively. PMID- 2898841 TI - Alternative model for Neisseria gonorrhoeae pilin variation. AB - The pilus of Neisseria gonorrhoeae, a dominant outer membrane organelle, is a major virulence factor. The pilus undergoes phase variation and antigenic variation has also been observed, both in vitro and in vivo. The current model of pilus variation invokes a gene conversion type recombination between a silent pilin locus and the pilin expression site. Experimental results which led to the creation of this hypothesis are reviewed and data are presented which support an alternative model based on DNA transformation. PMID- 2898842 TI - Tip proteins of pili associated with pyelonephritis: new candidates for vaccine development. AB - Escherichia coli strains associated with extra-intestinal infections frequently express carbohydrate binding adhesins which are present as minor components of pili. The adhesin protein, PapG, and at least two other minor pilus subunits, PapE and PapF, are associated with the tips of Gal alpha (1-4)Gal-binding Pap pili or P fimbriae of uropathogenic E. coli. The structural and antigenic variation of these tip-associated proteins is discussed and evidence is presented showing that serologically identical pili may contain antigenically distinct adhesins each capable of binding to a specific receptor. One approach to the purification of these tip-associated proteins is presented and involves complex formation with the periplasmic transport protein PapD. PMID- 2898844 TI - Progress towards a vaccine against enterotoxigenic Escherichia coli. AB - A variety of approaches are being investigated in the development of a vaccine against enterotoxigenic Escherichia coli (ETEC). These approaches include purified fimbriae vaccines, toxoid vaccines, live attenuated E. coli vaccine strains and ETEC antigens expressed in carrier organisms. Studies of the pathogenesis and immune response to ETEC indicate that development of a vaccine against human ETEC is a realistic goal but considerable work remains before this goal is realized. PMID- 2898843 TI - Safe, live Vibrio cholerae vaccines? AB - Mutants of Vibrio cholerae defective in intestinal colonization have been constructed. Characterization of these mutants has led to the identification of a gene cluster involved in the assembly of a pilus colonization factor called TCP. The tcp operon has been cloned and strains of V. cholerae have been constructed that overproduce this pilus and the B subunit of cholera toxin. Together these studies may contribute to the eventual construction of efficient live and killed, oral cholera vaccines. PMID- 2898845 TI - [Neuropathophysiological and neuroimmunopathological approaches to understanding the mechanisms and establishing the principles of the pathogenetic therapy of alcoholism]. PMID- 2898846 TI - [Perazine-induced agranulocytosis--case report]. AB - This complication normally arises between the 5th and 10th weeks of treatment and is most commonly seen in middle-aged and elderly women. The risk is estimated to be between 0.04% and 2%, depending on the type of medication and the method of assessment. The present report describes a 16-year-old boy who developed agranulocytosis after 4 weeks of treatment with perazine. The problem was complicated by acute toxoplasmosis. After perazine was discontinued the neutrophils recovered within 5 days; the boy did develop fever, but the infectious disease had a mild course. This case report once again confirms the importance of regular blood control during the early phases of treatment with psychopharmacological agents. PMID- 2898847 TI - [Pathogenic properties of freshly isolated strains of the pertussis microbe]. AB - The serovar composition, toxicity, virulence and lymphocytosis stimulating activity (LSA) of B. pertussis strains circulating in the 1980-ies were studied in comparison with the strains circulating in previous years. The study revealed changes in the toxic properties of B. pertussis: their decrease in the years of the intensive immunization of children against whooping cough and rise at the period when the number of immunized children was reduced. The toxic properties and LSA in most B. pertussis strains were less pronounced in the 1980-ies than in the 1960-ies. The serovar composition of the circulating strains remained stable for 15 years with the prevalence of serovar 1.0.3. PMID- 2898848 TI - [Effect of weather conditions in an epidemic season on the nature of the morbidity of hemorrhagic fever with renal syndrome]. AB - The epidemic manifestation of the most active natural foci of HFRS in the USSR on the territory of Bashkiria is described. The authors compare two epidemic seasons of 1975-1976 and 1977-1978. Besides the number of rodents, the rise of morbidity is influenced by their early multiplication and weather conditions. The early appearance of the stable snow cover facilitates a rapid drop in the number of NFRS cases as early as in October, while prolonged autumn with rains, snow, periods of thaw and ice-covered ground leads to a rise in NFRS morbidity occurring in autumn and winter and ending only in March. Weather conditions also influence the epidemiological structure of morbidity. PMID- 2898849 TI - [The structure of immunoregulatory cells as a reflection of their interaction in infectious diseases]. AB - Analysis of the structure of immunoregulatory cells (IRC) as the reflection of cell interaction in healthy persons and in patients with typhoid fever, tick borne encephalitis, or chronic opisthorchiasis has shown that the characteristics under study (information entropy, structural information, the coefficient of ecological-genetic correspondence) are highly sensitive and specific, which makes it possible to use them quite effectively for differentiating health from disease and for identifying this disease. The study of IRC structure as the reflection of cell interrelations helps evaluate the changes in the organization of IRC system as a whole in different infectious diseases. PMID- 2898850 TI - [Effect of phosphaden and unithiol on the cyclase system of the small intestine mucosa in rabbits in experimental salmonellosis]. AB - The study was made on 59 chinchilla rabbits. S. typhimurium 1847 live culture was introduced into the lumen of an isolated loop of the thin intestine. The activity of adenylate cyclase (AC), guanylate cyclase (GC), the levels of cyclic adenosine 3,5-monophosphate (cAMP), cyclic guanosine 3,5-monophosphate (cGMP), the activity of cAMP- and cGMP-phosphodiesterases were determined in the mucous membrane of the ligated part of the intestine. Considerable fluid accumulation in the loop, activation of AC and cGMP-phosphodiesterase, a rise in the level of cAMP and a drop in the level of cGMP in the mucosa of the ligated part of the intestine were registered. In one group of the animals phosphadene and in the other group unitiol were introduced into the infected intestinal loop; as a result, a decrease in the accumulation of fluid in the loop, on the average, by 40% and a tendency to an increase in the level of cAMP and a drop in the level of cGMP in the mucous membrane of the ligated part of the intestine were observed. Changes in the level of cGMP play, seemingly, a more important role in the development of diarrhea in salmonellosis. PMID- 2898851 TI - The use of gene probes to investigate the etiology of hyperlipidaemia and arterial diseases. PMID- 2898852 TI - Chronic GnRH administration in prepubertal male pigs. A model to evaluate the effects of GnRH treatment in cryptorchidism. AB - The effect of chronic pulsatile low-dose GnRH treatment on the juvenile testis and associated structures was evaluated in relation to hormonal parameters in the peripheral blood in the pig. Starting at 8 weeks of age, male pigs (crossbreds of Dutch Landrace and Yorkshire breeds) were injected 6 times daily im with 0, 75 or 250 ng GnRH/kg body weight during 4 weeks. Immediately after the treatment period, a GnRH stimulation test with 750 ng GnRH/kg iv was carried out. Samples for plasma LH, FSH, testosterone and 5 alpha DHT measurement were obtained weekly (basal level) and after GnRH stimulation. The pigs were castrated at 12 weeks of age and the weights and lengths of the testis, epididymis and cremaster muscle were recorded. Intratesticular testosterone and 5 alpha DHT concentrations were determined, and the testis and epididymis were evaluated for histological changes. Basal plasma hormone concentrations, intratesticular androgen concentrations and the response of the pituitary gland to stimulation had not been affected by GnRH treatment. Pigs receiving the higher treatment dose of GnRH showed less increase in testosterone levels in response to the stimulation dose at 12 weeks of age than the other pigs. Morphologically, no changes were observed in the epididymis and cremaster muscle after GnRH treatment and no signs of reactivation of structures that can provoke testicular descent could be seen. The development of the seminiferous epithelium was more advanced in the GnRH-treated groups, apparently in a dose-dependent manner. PMID- 2898853 TI - Peripheral and hepatic resistance to insulin and hepatic resistance to glucagon in uraemic subjects. Studies at physiologic and supraphysiologic hormone levels. AB - To characterize endogenous glucose production in uraemia, nondialyzed uraemic patients and controls were exposed to two major modulating hormones, insulin and glucagon. Nineteen uraemic and 15 healthy subjects underwent either a 2-step (insulin infusion rates: 0.45 and 1.0 mU.kg-1.min-1) or a 3-step (insulin infusion rates: 0.1, 0.2 and 0.3 mU.kg-1.min-1) sequential euglycaemic insulin clamp. Average steady state serum insulin concentrations were almost identical during all five infusion rates in uraemic patients (16, 22, 26, 31 and 66 mU/l) and controls (15, 19, 24, 33 and 68 mU/l). At all steps, insulin infusion was accompanied by significantly lower glucose disposal rates [( 3(-3)H]glucose) in uraemic patients compared with controls (P less than 0.05 or less). Moreover, the restraining potency of insulin on endogenous glucose production was much more prominent in healthy than in uraemic subjects at the lowest three infusion rates (0.6 +/- 1.0 versus 1.4 +/- 0.3 (mean +/- 1 SD), -0.3 +/- 0.7 versus 0.7 +/- 0.3, and -1.1 +/- 0.7 versus 0.2 +/- 0.6 mg.kg-1.min-1; P less than 0.05, P less than 0.01 and P less than 0.01, respectively), implying a shift to the right of the dose-response curve in uraemia. In contrast, basal values were comparable (2.4 +/ 0.3 versus 2.2 +/- 0.6 mg.kg-1.min-1) as the difference vanished at higher infusion rates, i.e. peripheral insulinaemia above approximately equal to 30 mU/l. Another 7 uraemic patients and 7 controls were infused with glucagon at constant rates of 4 or 6 ng.kg-1.min-1, respectively, for 210 min concomitant with somatostatin (125 micrograms/h) and tritiated glucose. The ability of glucagon to elevate plasma glucose was markedly attenuated in uraemic patients compared with controls during the initial 60 min of glucagon exposure. This difference was entirely due to diminished hepatic glucose production (3.5 +/- 0.8 versus 4.8 +/- 1.0 mg.kg-1.min-1; P less than 0.05). In conclusion, in addition to insulin resistance in peripheral tissues, uraemia is also associated with hepatic insulin resistance. Furthermore, glucagon challenge implies impaired early endogenous glucose release in uraemia suggesting a superimposed hepatic resistance to glucagon. PMID- 2898854 TI - Augmentation of glucose induced insulin secretion by pertussis vaccine, phentolamine and benextramine: involvement of mechanisms additional to prevention of the inhibitory actions of catecholamines in rats. AB - Pertussis vaccine, pertussis toxin, and the alpha-adrenoceptor blocking drug phentolamine augment glucose-induced insulin secretion. The present study was carried out to determine the relationship between this action and the ability of these agents to prevent the inhibitory actions of adrenaline. Pertussis vaccine augmented glucose-induced insulin secretion in rat islets ex vivo and prevented the inhibitory actions of adrenaline and clonidine. Incubation of islets with phentolamine or the irreversible alpha-adrenoceptor blocking agent benextramine also augmented glucose-induced insulin secretion. However, the alpha-adrenoceptor blocking drugs idazoxan, yohimbine or phenoxybenzamine, in concentrations that prevented the inhibitory effects of adrenaline and/or clonidine, did not modify glucose-induced insulin release in vitro. Benextramine (1 X 10(-5) mol/l) blocked the inhibitory effect of clonidine, whilst having no significant effect on the response to adrenaline. It is concluded that stimulation of insulin secretion by certain alpha-adrenoceptor blocking drugs can be dissociated from their alpha adrenoceptor properties. The ability of pertussis vaccine, phentolamine or benextramine to augment glucose-induced insulin release in vitro is unlikely to be due to the prevention of the inhibitory action of endogenous catecholamines. PMID- 2898855 TI - Somatostatin reduces posthypoglycemic insulin resistance in insulin-dependent diabetes mellitus. AB - In order to study whether somatostatin reduces posthypoglycemic insulin resistance, hypoglycemia was induced between 7.00 and 8.00 h by an iv infusion of insulin with and without somatostatin (250 micrograms/h) in 6 male patients with insulin-dependent diabetes mellitus (IDDM). Exogenous glucagon was infused to substitute for the suppression of its endogenous release (1.0-1.5 ng.kg-1.min-1). Insulin resistance was assessed by a somatostatin-insulin-infusion test (SIGIT) between 11.00 and 15.00 h. In the study without hypoglycemia, blood glucose was kept close to 6 mmol/l from 8.00 h until start of the SIGIT. In both hypoglycemic studies similar nadir blood glucose levels were achieved and hypoglycemia evoked the same increase of plasma epinephrine and cortisol, whereas plasma glucagon remained at its basal level. The growth hormone response to hypoglycemia was suppressed by somatostatin. At the onset of the SIGIT, the plasma levels of the counterregulatory hormones had returned to basal, and blood glucose and plasma free insulin concentrations were almost identical. During the SIGIT there were no differences in plasma free insulin or counterregulatory hormone levels. Insulin resistance, as seen following hypoglycemia, was not demonstrable in the study with somatostatin. It is concluded that somatostatin reduces insulin resistance following hypoglycemia in patients with IDDM. It is therefore suggested that an analogue with a specific GH release inhibiting property may be useful in reducing glycemic instability when given as adjunct therapy to insulin in patients with labile glycemic control. PMID- 2898856 TI - Blood levels, clearance rates and effects of epinephrine and norepinephrine on insulin and metabolites during alpha- and beta-adrenergic blockade in cattle in vivo, and in vitro degradation of dopamine in bovine blood. AB - To study possible modifications of norepinephrine and epinephrine kinetics (metabolic clearance rate and half-times) by inhibition of binding to alpha- and/or beta-adrenergic receptors, norepinephrine and epinephrine were iv infused in the absence or presence of the alpha-adrenergic blocking agent phentolamine, the beta-adrenergic blocking agent propranolol, and during the combined administration of phentolamine and propranolol. In addition, recovery experiments were performed to investigate the in vitro degradation of dopamine, norepinephrine and epinephrine. Blood levels and kinetics of epinephrine were not modified by alpha- and beta-adrenergic blockade, whereas norepinephrine clearance was reduced by alpha-adrenergic blockade, and was greater than epinephrine clearance. alpha- and beta-adrenergic blockade markedly modified insulin, glucose and non-esterified fatty acid responses to epinephrine and norepinephrine. Norepinephrine and epinephrine could fully be recovered when added to bovine blood plasma. In contrast, dopamine obviously was immediately destructed by bovine, but not by human blood plasma, and should therefore barely be detectable in blood of cattle in vivo. PMID- 2898858 TI - Distribution of adult T-cell leukemia and HTLV-I carriers in Kochi prefecture, Japan. PMID- 2898857 TI - Immunocytochemical changes in hypothalamic and pituitary hormones after acute and prolonged stressful stimuli in the anestrous ewe. AB - We studied the effect of short (acute (20 min/h, for 4 h) and intermittent, long term (20 min/h for 9 h on 3 consecutive days) electric foot shocks on the immunocytochemical localization of CRH and SRIH in the hypothalamus and of ACTH, beta-endorphin, GH and PRL in the pituitary of the anestrous ewe. Acute stress greatly reduced immunoreactive (ir) CRH in the median eminence and cellular irACTH, beta-endorphin and PRL, as well as the proportion of these cell types in the pituitary. A slight reduction of irSRIH in the median eminence was also observed. After long-term stress, reduction of irCRH in the median eminence was still observed. However, ACTH/beta-endorphin cells in the pituitary gland displayed increased secretory activity, manifested by hypertrophy and hyperplasia. A marked depletion of irSRIH in the nerve terminals of the median eminence was observed. The proportion of PRL cells but not their ir content returned to control levels. No effects were observed on the features of the GH cells. This study indicates that there are differences in the effect of short- and long-term stressful stimuli on the activity of hormonal systems in the anestrous ewe. Short-term stress immediately activates the CRH/ACTH/beta endorphin axis. Prolonged stress appears to augment the activation of the SRIH hypothalamic system and probably has a restraining effect on ACTH/beta-endorphin release. PMID- 2898859 TI - A comparison of betaxolol and timolol in open angle glaucoma and ocular hypertension. AB - In a randomized, double-masked study, 41 patients with primary open-angle glaucoma or ocular hypertension were treated with betaxolol 0.5% or timolol 0.5% drops for 26 weeks. The average decrease in intraocular pressure (IOP) over the total study period was significant with both betaxolol (-6.3 mmHg) and timolol ( 7.2 mmHg) in patients receiving no adjunctive therapy. There was no difference between betaxolol and timolol with respect to changes from baseline IOP. Significantly decreased mean brachial arterial pressure (MAP) was seen only with timolol, although the difference between the two groups was not significant. Pulse, pupil size, and basal tear secretion were unchanged in both groups. Burning upon instillation of the drops was more frequent with betaxolol. PMID- 2898860 TI - Relations between blood flow and mucociliary activity in the rabbit maxillary sinus. AB - The effects of two sympathomimetic drugs on mucociliary activity and mucosal blood flow in the rabbit maxillary sinus were investigated by using a photo electric technique (mucociliary activity) and laser Doppler flowmetry (blood flow). The responses produced were compared with effects of ligation of the external carotid artery. The alpha 1-agonist phenylpropanolamine (0.1-100 micrograms/kg) had no effect on the mucociliary activity, whereas the blood flow was reduced by 33.8 +/- 8.9% (mean +/- SE) when the dose was 100 micrograms/kg. The alpha 2-agonist xylometazoline (0.01-10.0 micrograms/kg) reduced mucociliary wave frequency by 21.6 +/- 4.6% (mean +/- SE) (maximum) for the dose 10 micrograms/kg. The blood flow was reduced by xylometazoline in the interval 1.0 to 10.0 micrograms/kg, with a maximum decrease of 65.8 +/- 2.6% (mean +/- SE) for the dose of 10 micrograms/kg. Ligature of the external carotid artery reduced blood flow by 76.0 +/- 4.6% (mean +/- SE), but did not significantly influence the mucociliary wave frequency. It is concluded that the decrease in mucociliary activity induced by alpha 2-adrenoceptor agonists is not due to a reduced blood flow. PMID- 2898861 TI - DNA typing of a cystic fibrosis family with borderline sweat tests. PMID- 2898862 TI - Long-term use of somatostatin analogue SMS 201-995 in the treatment of hypoglycaemia due to nesidioblastosis. AB - An infant presented with hypoglycaemia secondary to nesidioblastosis. Subtotal pancreatectomy failed to prevent recurrent post-operative hypoglycaemia. Subcutaneous somatostatin analogue (SMS 201-995) was shown to increase the blood concentrations of glucose and B-hydroxybutyrate while lowering serum insulin levels. Regular use of somatostatin analogue was helpful in long term management without causing significant side effects. PMID- 2898863 TI - [Studies on crystal structures and structure-activity relationships of the 4 substituted fentanyl derivatives]. PMID- 2898864 TI - New selective dopamine D-2 antagonists as antipsychotic agents. Pharmacological, chemical, structural and theoretical considerations. PMID- 2898865 TI - Effects of ganglion blocking agents on post-train facilitation in the rabbit superior cervical ganglion. AB - The effect of ganglion blocking agents, hexamethonium and tubocurarine, on post train facilitation and ganglionic transmission was studied and compared in isolated superior cervical ganglion of the rabbit, using electrophysiological technique--the conditioning-testing methodology. The preganglionic nerve trunk was stimulated, with either a single unconditioned stimulus (UR)-or a train of conditioning stimuli at 10 or 30 Hz, followed by a post-train test stimulus (PTR). The transmitted postganglionic, compound action potential (PCAP) was recorded following single and trains of stimuli, in the presence and absence of ganglion blocking drugs, hexamethonium (1-100 microM) and tubocurarine (1-100 microM). Hexamethonium and tubocurarine produced concentration-dependent reduction in the amplitude of the transmitted PCAP, increased post-train facilitation values and proportionately reduced those of the subliminal fringe (SF). The mean IC50 values (concentration to produce 50% block of PCAP) of hexamethonium and tubocurarine-induced blockade of the single unconditioned response were 15 +/- 1 microM and 26 +/- 2 microM (n = 6, P less than 0.01) respectively. A dose-ratio (tubocurarine)/hexamethonium) of 1.7 was obtained. PMID- 2898866 TI - Somatostatin-induced inhibition of lipolysis: in vitro studies. AB - Incubation of epididymal fat tissue slices with somatostatin (SS) led to the inhibition of epinephrine-induced release of free fatty acids (FFA) and glycerol in a dose-dependent manner. The SS administration did not suppress the lipolysis evoked by dibutyryl cAMP. The experimental findings indicate that SS exerts an inhibition of catecholamines-induced lipolysis at the level of adipocytes although the mechanism of action requires further investigations. PMID- 2898867 TI - Effect of intraarterial somatostatin infusion on SMA blood flow. AB - Experiments were carried out on anaesthetized cats to study the effect of somatostatin on the mesenteric circulation. Intraarterial infusions of somatostatin were applied into the superior mesenteric artery. The effect of atropine, propranolol and phentolamine were investigated. Catecholamine release or uptake of the mesenteric vascular bed during somatostatin infusions were also measured. We found dose dependent vasodilatory effect of somatostatin on the mesenteric vasculature that was not influenced by atropine and by the adrenoreceptors or by denervation. A direct effect of somatostatin on the vascular smooth muscle membrane is assumed. PMID- 2898868 TI - Effects of neurohypophyseal hormones on food-reinforced classical conditioning in the rat. AB - The effects of different doses of lysine vasopressin (LVP) and oxytocin (OXT) were studied on the six-day acquisition or extinction of a food-reinforced classical conditioning reflex (conditional stimulus: light) when intraperitoneal (ip.) injections were carried out 20 min prior to the behavioural sessions. The highest (600 mU/kg) dose of LVP inhibited acquisition, and all LVP doses tested (150, 300 and 600 mU/kg) facilitated the extinction of conditioned behaviour. These same mU doses of OXT did not significantly affect the food-reinforced conditioning, although a consequent tendency towards increased performance (the opposite action to vasopressin) was observed. When 2.5 or 25 micrograms/kg doses of desglycinamide-arginine-vasopressin (DGAVP), a 500 micrograms/kg dose of prolyl-leucyl-glycinamide (PLG) or a 1200 mU/kg dose of OXT was injected during the extinction sessions, 2.5 micrograms/kg DGAVP and 1200 mU/kg OXT significantly facilitated extinction; the other treatments were without effect. LVP in a dose of 300 or 600 mU/kg and OXT in a dose of 300, 600 or 1200 mU/kg did not influence the food intake of 22 h food-deprived rats in a nonconditional situation. The present results indicate that the effects of LVP and OXT on memory display reinforcement-dependent characteristics, and are thus indirect or non-specific in nature. PMID- 2898869 TI - Pharmacological profile and mechanism of action of antidepressant drugs. PMID- 2898870 TI - Tardive dyskinesia. AB - Tardive dyskinesia (TD) is a syndrome of involuntary movements that develops in predisposed individuals during neuroleptic drug treatment, with an average prevalence of 15%. Neuroleptic (antidopaminergic) drugs are the predominant etiological factor. Although no simple correlation can be established, both dosage and treatment duration seem to be of importance for the development of dyskinesia. It is still uncertain whether some neuroleptics carry a higher risk than others, but it appears that the atypical neuroleptic clozapine, which causes no or minimal dystonia, parkinsonism, or akathisia, also carries no or minimal risk of TD. The pathophysiological mechanisms underlying TD are unclear. The traditional dopamine hypersensitivity theory is no longer viable, whereby new hypotheses have been advanced: TD can be due to the blockade of a subset of striatal dopamine receptors, while parkinsonism is due to the blockade of another such subset, and/or can be due to a reduced GABA turnover in a subgroup of neurons connecting striatum with globus pallidus and substantia nigra. TD is best prevented by a course of neuroleptic medication involving as little antidopamine effect as possible, including minimal doses and shortest possible length of treatment. The main TD treatment principle consists of a gradual dose reduction, possibly over years. It should be added, however, that more recent investigations indicate that traditional antidopaminergic treatment in moderate doses may be safely continued over a long period without an increased risk of TD progression. PMID- 2898871 TI - Topographical distribution of absolute alpha-power in the EEG and psychopathology in schizophrenic outpatients. AB - In 36 schizophrenic outpatients (Research Diagnostic Criteria) under neuroleptic maintenance treatment the EEG was recorded under resting conditions. The absolute alpha-power (7.5-13 Hz) was estimated by Fast Fourier Transform as the mean of 300 2-second epochs for the leads F3/A1, F4/A2, 01/A2 and 02/A2. Two lateralization quotients (anterior, posterior) and two anteriorization quotients (left, right) were calculated from the absolute alpha-power. Clinical status was assessed cross-sectionally with BRPS, GAS and CGI. The main findings are: 1) A linear relationship between the left/right ratio of absolute alpha-power over posterior regions and anxiety/depression--the more the alpha-power is left lateralized, the higher the anxiety/depression score; 2) a curvilinear, inverted U-shaped relationship between the left/right ratio of absolute alpha-power over posterior regions and the score of schizophrenia-specific symptomatology; 3) the amount of daily neuroleptic dose (mgCPZ) has no impact on EEG-parameters. Results are discussed with respect to hemisphere asymmetry models of psychopathology. PMID- 2898872 TI - [Measurement of pain intensity in surgery patients for the purpose of evaluating the effects of analgesics]. PMID- 2898873 TI - [Cryptorchism III. A: The gubernaculum in testicular descent. Experimental study]. PMID- 2898874 TI - [Cryptorchism III. B: Qualitative and quantitative changes in experimentally induced cryptorchid testis]. PMID- 2898875 TI - [Indications for the interlocking nailing in open fractures]. AB - The history of intramedullary nailing leads us to assume that septic complications arising from the treatment of open fractures through marrow nailing are largely due to reaming and need no longer to a full extent be put down to treatment by locking nailing. Locking nailing of an open fracture (all three degrees) of the femur can be recommended as long as the periosteum is not exposed over large segments, and coverage with soft tissue is possible. Locking nailing of the lower leg can only be recommended with open fractures of the first degree. With fractures of the second and third degrees the fixateur externe is the treatment of choice. PMID- 2898876 TI - [Para-articular fracture of the hip joint in the aged--an indication for immediate operation?]. AB - 177 patients with fractures near the hip joint were operated on between January 1983 and December 1985. The fractures were treated with Ender pinnings, total endoprostheses and dynamic hip screws (compression screw fixation). Up to June 1984 surgery was performed after the patients had been allowed a stabilisation phase of 4 days on the average, but from July 1984 onwards we aimed at performing immediate surgery within 12 hours. The second group was compared with the first group in a retrospective study in respect of recumbent period and mortality (hospital mortality and mortality after 8 months). The period during which the patients had to remain recumbent in the hospital was found to be considerably shorter, but there were no statistically significant differences in respect of mortality. The causes and consequences are discussed. PMID- 2898877 TI - [Subcutaneous tendon ruptures of the upper arm]. AB - 25 subcutaneous tendon ruptures of the upper arm were operatively treated between 1982 and 1985. The long biceps tendon was ruptured fifteen times, the distal biceps tendon eight times and the triceps tendon twice. Operative procedures and the functional results are described. The follow-up investigation was undertaken on an average of 14 months after operation. Mechanism of injury and variations of histological findings in the different tendons are compared. The functional results are good. The operative treatment of subcutaneous tendon ruptures of the upper arm is therefore recommended. PMID- 2898878 TI - [Isolated fractures of the shoulder blade in childhood and adolescence]. AB - Fractures of the scapula in childhood and youth are very rare injuries. Despite the few number of cases one can clearly distinguish, with regard to the cause of the accident, the sort of forces involved and the type of fracture, between those injuries received by adults and those of children. In the case of children and youths isolated scapular injuries and a larger number of isolated fractures of the acromial and the coracoid processes can be found. For an accurate diagnosis a thorough radiological examination must be undertaken, and if necessary further special x-ray projections or on-target x-ray spot exposures. PMID- 2898879 TI - [Intra- and postoperative fractures in alloarthroplastic knee replacement]. AB - In contrast to aseptic and septic loosening intra- and postoperative fractures of the femur rsp. the tibia represent rare complications of total knee replacement. Between 1971 und 1986 we implanted altogether 163 knee prostheses; 7 times (6 patients) happened a fracture of the femur or the tibia (3 times intra-, 4 times postoperatively). Those complications are described by special case reports. Intraoperative fractures are mainly referred to not very subtle operative technique. Concerning postoperative fractures prosthesis specific factors and non specific circumstances have to be differentiated. PMID- 2898880 TI - [Concentration of metronidazole in bones]. AB - Bone and serum concentrations of metronidazole were determined in 16 patients receiving a single dose of metronidazole before total hip replacement. The patients gave written informed consent to the procedure. Bone specimens were taken during the operation. Metronidazole was determined in serum and bone by high-performance liquid chromatography (HPLC). 30 to 85 minutes after i.v. infusion of 0.5 g metronidazole (infusion period 20 min.) concentrations in bone ranged from 3 to 25 mg/l. Metronidazole appears suitable for treatment of mixed infections of bone by anaerobes with proven sensitivity. Metronidazole should always be given in combination with another suitable antibiotic. PMID- 2898881 TI - [Fixation of the cervical spine with a new halo fixation system]. AB - The stable fixation of the cervical spine by means of a halo external fixator is superior in terms of stability compared with alternative methods. A new Halo external fixator system is being introduced which enables uncomplicated handling with which optimal possibilities for positional correction are achieved by means of lockable ball joints. By using carbon enhanced connection rods radiolucency is given. PMID- 2898883 TI - [A simple instrument for distal intramedullary nailing]. PMID- 2898882 TI - [The infected hip joint]. AB - The deep infection of a hip joint (after operative treatment of a fracture, after corrective osteotomy or as a haemtogeneous joint infection) is a severe, locally and systemically dangerous sickness; her treatment ist difficult because of the multifactorial genesis. In the accident hospital of Tubingen were treated 35 empyemas of hip joint (excluding after implantation of a prosthesis) within 10 years. The therapeutic management normally needs three steps: 1. Control of acute empyema or septicaemia (Debridement, Drainage, antibiotic treatment) 2. Achievement of fracture or osteotomy stability (by changing of osteosynthesis or bone-grafting under continuous drainage) 3. Definitive healing by removing of metal, resection of a destroyed or necrotic femoral head, by arthrodesis of the joint or--in special cases--by implantation of a prosthesis. In this way it was possible to control all of the 35 deep hip joint infections and to maintain function in 28 cases. Within the follow up (in the average 4 years) all the patients were free of infection. PMID- 2898884 TI - [The synthesis of catecholamines in bovine iris in vitro]. PMID- 2898885 TI - [Buccal ulceration in a case of periarteritis nodosa]. PMID- 2898886 TI - [Clinical studies against chronic prostatitis and prostatitis-like syndrome (2). Evaluation of therapeutic effect]. AB - We treated 229 cases of chronic prostatitis (bacterial in 29, non-bacterial in 200) and 238 cases of prostatitis-like syndrome and evaluated the clinical efficacy. Clinical efficacy was seen in 77.3% of the chronic prostatitis cases (82.8% bacterial, 76.5% non-bacterial) and 53.8% of the prostatitis-like syndrome cases, with a statistical difference between these two types of disease (p less than 0.01). Treatment included chemotherapy, anti-inflammation agents and minor tranquilizers. None of them were effective against the prostatitis-like syndrome. On the other hand, combination usage (chemotherapies and anti-inflammation agent) was satisfactory on chronic bacterial prostatitis. Also on chronic non-bacterial prostatitis, chemotherapy was significantly effective (p less than 0.05%). Chemotherapeutic effectiveness against chronic prostatitis (both bacterial and non-bacterial) was high with sulfamethoxazole-trimethoprim, tetracyclines, cephalosporins, nalidixic acid and penicillins in this order. There was no difference among these drugs. Prostatic massage was generally effective especially for chronic non-bacterial prostatitis (p less than 0.05) and prostatitis-like syndrome (p less than 0.01). Light psychological treatment was significantly effective toward some cases of prostatitis-like syndrome with strong psychosomatic factors (p less than 0.01). PMID- 2898887 TI - [Risk factors of undescended testis]. AB - A study on possible association of maternal factors with undescended testis was undertaken. A comparison was made using mothers of boys with the disease (No. = 108) and mothers of boys without the disease (No. = 108). The boys without the disease were selected from outpatients by individually matching the birth year with the case. A smaller proportion of mothers having babies with the disease experienced vomiting during the index pregnancy (the estimated relative risk RR = 0.51, P = 0.02). A larger proportion of them had delivered by vacuum extractor delivery, cesarean section, or breech extraction (RR = 2.10, P = 0.04). A higher proportion of cases were complicated with inguinal hernia (RR = 9.00, P = 0.03), congenital cardiac diseases (RR = infinity, P = 0.008), or other various kinds of congenital disorders. A larger proportion of these mothers had never breastfed for the cases (RR = 3.75, P = 0.02). Exposure to external estrogen in the utero was not noted to be associated with undescended testis. PMID- 2898889 TI - Pharmacologic management of chronic pain in the cancer patient. PMID- 2898888 TI - [A case of Kallmann's syndrome]. AB - A 13-year-old boy visited our hospital with the chief complaint of right undescended testis and retardation of secondary sexual characteristics. Central hyposmia and sensorineural hearing loss were found. The plasma levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were low and the reaction to LH-releasing hormone (RH) test was poor. After repeated LH-RH tests, a good response in plasma levels of LH and FSH was observed. The diagnosis of Kallmann's syndrome was made from the above findings. The testicular biopsy specimen from him showed immature testis without any developed Leydig or Sertoli cells. To induce secondary sexual characteristics, 2000 I.U. of human chorionic gonadotropin (hCG) was administered to him twice a week for 3 months. The administration of hCG resulted in elevation of plasma testosterone level, swelling of testes, increase of pubic hair and spurt of height. PMID- 2898890 TI - Effect of drug therapy on survival in chronic congestive heart failure. AB - A review of the current evidence on the effects of various agents on survival among patients with congestive heart failure (CHF) suggests that angiotensin converting enzyme inhibitors probably offer the greatest potential for benefit. Trials undertaken before the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) revealed favorable trends among patients in New York Heart Association functional classes II to IV who received angiotensin-converting enzyme inhibitors. Data from CONSENSUS clearly demonstrate that enalapril reduces mortality rates among patients in New York Heart Association class IV, but conclusions regarding effects in patients with mild or moderate CHF must await the results of future studies. In contrast, the large data base on alpha adrenergic blockers suggests that these drugs are not likely to improve survival. Information on inotropic agents is sparse, but it is possible that these drugs may not improve survival and, in fact, may have a harmful effect. Mortality data on CHF patients treated with beta blockers and calcium channel blockers are likewise limited; conclusions concerning effects on survival must be postponed until further studies are conducted. Many of the investigations undertaken thus far to examine survival in patients with CHF have been small and of short duration, so any comparisons of the effects of various drugs must be interpreted with caution. PMID- 2898892 TI - Adrenal sympathetic efferent nerve and catecholamine secretion excitation caused by capsaicin in rats. AB - Capsaicin enhances adrenal medullary catecholamine secretion. The participation of the central nervous system on this enhancement by capsaicin was investigated in alpha-chloralose-urethan- or halothane-anesthetized rats. Intravenous administration of capsaicin caused a rapid and marked increase in adrenal sympathetic nerve activity. The nerve activity began to show an increase with the administration of capsaicin at a dosage of 20 micrograms/kg and significantly increased with a dosage of 200 micrograms/kg, i.e., capsaicin was found to cause a dose-dependent increase in adrenal nerve activity. Cholinergic blocking with hexamethonium bromide and atropine sulfate (1 and 5 mg/kg iv, respectively) attenuated the adrenal epinephrine secretion caused by capsaicin. The direct action of capsaicin on adrenal catecholamine secretion was examined using a retrograde perfusion system of left adrenal gland. Up to 8.2 X 10(-5) M capsaicin did not enhance catecholamine secretion from the adrenal gland. These results suggest that the enhancement of physiological catecholamine secretion by capsaicin is mainly through activation of the central nervous system. PMID- 2898891 TI - Human T-cell lymphotropic virus I and adult T-cell leukemia: report of a cluster in North Carolina. AB - PURPOSE: Human adult T-cell leukemia-lymphoma is a malignant, proliferative disease of CD4+ lymphocytes associated with infection with human T-cell lymphotropic virus type I (HTLV-I). Following the presentation of a patient who was infected with the virus, we undertook a study of his family members and sexual contacts to see if a cluster of infected persons could be identified. CASE REPORT: A black heterosexual North Carolina native with a history of drug abuse presented with jaundice, and pancytopenia subsequently developed. He then became hypercalcemic and leukemic, with high numbers of circulating, morphologically abnormal CD4+ lymphocytes. RESULTS: As determined by radioimmunoassay and immunoblot analyses, the serum of the index case contained antibodies against core proteins (p19 and p24) of HTLV-I. When cultured in vitro with interleukin-2, the lymphocytes expressed HTLV-I specific core proteins. The virus recovered from these T cells was transmitted to cord blood T cells, which became immortalized for continuous growth in vitro, expressed HTLV-I p19 protein, and displayed characteristic C-type particles by electron microscopy. Studies of family members and sexual contacts, all of whom were black, heterosexual central North Carolina natives, revealed five of 28 whose serum had anti-HTLV-I antibodies as determined by radioimmunoassay and immunoblot. Neither the patient nor the seropositive family/contacts had antibodies against human immunodeficiency virus proteins. Four of the six people with HTLV-I infection had no history of intravenous drug abuse. Three of the five seropositive family/contacts had circulating, morphologically abnormal lymphocytes suggestive of "preleukemic" or "smoldering" human adult T-cell leukemia-lymphoma. PMID- 2898893 TI - Physiological insulin action is opposed by beta-adrenergic mechanisms in dogs. AB - To investigate the possible role of adrenergic mechanisms in modulating glucose homeostasis during physiological insulin changes, we studied the effects of alpha , beta-, or combined alpha- and beta-adrenergic blockade on glucose production (Ra) and utilization (Rd) via isotope ([3-(3)H]glucose) dilution during nonstressful, nonhypoglycemic conditions in response to physiological insulin changes in conscious dogs. Without adrenergic blockade, infusion of insulin at 0.275 mU.kg-1.min-1 (control) caused glucose to fall from 92 +/- 4 to 82 +/- 4 mg/dl over 30 min, because of transient fall in Ra from 2.8 +/- 0.4 to 2.3 +/- 0.3 mg.kg-1.min-1, which recovered to base line by 30 min. There was a later rise in Rd to 3.9 +/- 0.4 mg.kg-1.min-1 at 45 min, but no counter-regulatory hormonal changes (glucagon, cortisol, epinephrine, and norepinephrine) to account for these findings in glucose kinetics. alpha-Blockade alone led to an initial rise in base-line insulin and consequent fall in glucose, associated with a transient fall in Ra but no change in Rd; infusion of insulin led to a further small fall in glucose, with no change in Ra, but with a rise at 30 min in Rd similar to controls. beta-Blockade alone led to an initial fall in insulin and modest rise in glucose; insulin infusion led to a greater rate of fall in glucose than in controls (from 112 +/- 6 to 78 +/- 7 mg/dl over 30 min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898894 TI - Effects of somatostatin and glucose infusion on glucose kinetics in fetal sheep. AB - We examined the contribution of glucose, independently of insulin, on fetal glucose kinetics in the sheep by infusing somatostatin (SRIF), followed by SRIF plus glucose (protocol A) or reversing the initial infusion sequence (protocol B). In protocol A (n = 8), infusion of SRIF at 200 micrograms/h decreased plasma insulin (IRI) and blood glucose (G) by 2.8 +/- 1.0 microU/ml and 1.34 +/- 0.2 mg/dl from their respective basal concentrations of 6.8 +/- 1.4 microU/ml and 16.47 +/- 0.91 mg/dl (P less than 0.05; P less than 0.005). There were no significant changes in plasma glucagon (IRG) or the rates of umbilical G uptake or of G utilization, but G turnover decreased by 1.77 +/- 0.34 mg.kg-1.min-1 (P less than 0.005). Addition of G at a rate of 5.6 +/- 0.8 mg.kg-1.min-1 had no effect on IRI and IRG. Total G uptake (G infusion rate plus umbilical G uptake) increased from 6.37 +/- 0.77 to 10.25 +/- 1.0 mg.kg-1.min-1 (P less than 0.01), despite suppression of umbilical G uptake by 33%. Fetal G reached a new steady state of 23.08 +/- 1.37 mg/dl, and G turnover increased by 4.81 +/- 0.96 mg.kg 1.min-1 from its SRIF-induced nadir (P less than 0.005). Since G concentration was maintained at steady state, the rate of G utilization was equivalent to the rate of total G uptake, an increase of 60% from basal despite suppressed IRI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898895 TI - Functional somatostatin receptors on a rat pancreatic acinar cell line. AB - Somatostatin receptors from a rat pancreatic acinar cell line, AR4-2J, were characterized biochemically, structurally, and functionally. Binding of 125I [Tyr11]somatostatin to AR4-2J cells was saturable, exhibiting a single class of high-affinity binding sites (Kd = 0.55 +/- 0.06 nM) with a maximal binding capacity of 258 +/- 20 fmol/10(6) cells. Somatostatin receptor structure was analyzed by covalently cross-linking 125I-[Tyr11]somatostatin to its plasma membrane receptors. Gel electrophoresis and autoradiography of cross-linked proteins revealed a peptide (Mr 80,000) containing the somatostatin receptor. Somatostatin inhibited vasoactive intestinal peptide (VIP)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation in a dose-dependent manner. The concentration of somatostatin that caused half-maximal inhibition of cAMP formation (IC50 = 0.4 nM) was close to the receptor affinity for somatostatin. Pertussis toxin pretreatment of AR4-2J cells prevented somatostatin inhibition of VIP-stimulated cAMP formation as well as somatostatin binding. We conclude that AR4-2J cells exhibit functional somatostatin receptors that retain both specificity and affinity of the pancreatic acinar cell somatostatin receptors and act via the pertussis toxin-sensitive guanine nucleotide-binding protein Ni to inhibit adenylate cyclase. PMID- 2898896 TI - Immunoneutralization of somatostatin and neurotensin: effect on gastric acid secretion. AB - Cell lines producing monoclonal antibodies to somatostatin and neurotensin, designated S-10 and NT-C5, respectively, have recently been generated. The purpose of the present immunoneutralization study in urethan-anesthetized gastric fistula rats is 1) to examine the ability of these antibodies to block the inhibitory effect of their target peptides on meal-stimulated gastric acid secretion and 2) to use these antibodies as probes to determine whether somatostatin and/or neurotensin are involved in the inhibition of gastric acid secretion produced by intraduodenal, intra-ileal, and intracolonic fat infusions. The results demonstrate that both S-10 and NT-C5 successfully bound exogenous somatostatin and neurotensin in vivo. S-10 but not NT-C5 prevented the inhibition of gastric acid secretion produced by intraduodenal fat. NT-C5 but not S-10 prevented the inhibition of gastric acid secretion produced by intra-ileal fat. Neither S-10 nor NT-C5 prevented the inhibition of gastric acid secretion produced by intracolonic fat. We conclude that somatostatin is associated with proximal and neurotensin with distal small bowel intestinal fat-induced inhibition of gastric acid secretion. PMID- 2898897 TI - ATL opportunistic infections. PMID- 2898898 TI - [Roentgen photogrammetry of the artificial hip joint acetabulum]. PMID- 2898899 TI - Interactions of ACTH4-10 and ACTH1-24 with L-[3H]glutamate binding sites and GABA/benzodiazepine/picrotoxin receptor complexes in vitro. AB - The effects of ACTH4-10 and ACTH1-24 on L-[3H]glutamate (Glu) binding sites and GABA/benzodiazepine/picrotoxin receptor complexes in vitro were investigated. ACTH4-10 and ACTH1-24 inhibited [3H] Glu and [3H] muscimol binding concentration dependently, while [3H] flunitrazepam (FNP) and [35S] t butylbicyclophosphorothionate (TBPS) binding were not affected. These ACTH fragments also inhibited GABA-stimulated [3H] FNP binding. These results suggest that ACTH and its fragments may act as anticonvulsants by antagonizing glutamate binding, their interaction with GABA-A sites may relate to the other central nervous effects of ACTH than the anticonvulsant activity. PMID- 2898900 TI - Enhancement by pain and stress of analgesia produced by epidural sufentanil in the rat. AB - This study examined whether pain or stress can enhance the analgesic effects of spinally administered opiates. The experiments determined the effects of mechanically produced pain and of the stress of being restrained on the analgesic effects of 0.63 microgram of epidural sufentanil in rats using a tail-withdrawal procedure. The painful, as well as the stressful, conditions appeared to increase the duration of opiate analgesia 3.7- and 3.0-fold, respectively. The data offer initial evidence that pain and other stressful conditions can enhance the analgesia produced by spinally administered opiates. PMID- 2898901 TI - Analgesic and respiratory effects of epidural sufentanil in patients following thoracotomy. AB - Immediately following thoracotomy, 22 patients were entered into a randomized, double blind study comparing the effects of three lumbar epidural doses of sufentanil on postoperative pain and respiratory pattern. Patients were given either 30 micrograms (group I), 50 micrograms (group II), or 75 micrograms (group III) of epidural sufentanil in 20 ml N saline. Repeat doses were given on request for the 24-h study period. Linear analogue pain score (PS), heart rate (HR), and mean arterial pressure (MAP) were measured at 15-min intervals after each dose. Respiratory depression was assessed by the presence of: 1) slow respiratory rate (SRR--less than 10 breaths per minute for greater than 5 min), 2) apnea (AP- cessation of tidal ventilation for greater than 15 s), and 3) increased PaCO2 in arterial blood gases (ABG) drawn at regular intervals. SRR and AP were measured using respiratory inductive plethysmography (RIP). A further group of ten patients (group IV) underwent preoperative RIP monitoring during sleep and in the absence of any drug. Maximum analgesia was achieved within 15 min after a dose of sufentanil for all groups. Analgesia was not significantly prolonged by increasing the dose of sufentanil. SRR occurred in all four groups (group I: 2/9; group II: 2/6; group III: 7/7; group IV: 2/10 P less than 0.05 I, IV:II, I, IV:III, II:III). The number of episodes of SRR/hr was highest in group II (group I: 0.6 +/- 0.8, group II: 4.12 +/- 0.6, group III: 1.8 +/- 2.0, group IV: 0.5 +/- 0.2) (NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898902 TI - Structure:action relationships among some desacetoxy analogues of pancuronium and vecuronium in the anesthetized cat. AB - The hypothesis that the neuromuscular blocking potency of pancuronium and vecuronium depends on the two acetylcholine moieties present at positions 3 and 17 was tested in cats by examining the neuromuscular profile of several desacetoxy analogues. Blockade of sciatic nerve-induced contraction of the tibialis and soleus muscles, as well as the effects on vagal-induced bradycardia and on sympathetically induced contractions of the nictitating membrane, were studied. The bis-desacetoxy analogue of pancuronium (ORG 7931) was one-fifth as potent as the parent compound as a neuromuscular blocking drug and as a vagolytic agent, but the neuromuscular block was faster in onset and shorter in duration than that produced by pancuronium. The desacetoxy analogues of vecuronium (ORG 8730 and ORG 8764) also were less potent neuromuscular blocking drugs, and, in addition, produced more vagal block than did vecuronium itself. The neuromuscular block produced by these desacetoxy analogues was of more rapid onset and shorter duration than that produced by vecuronium. The results thus showed that the greater neuromuscular blocking potency of pancuronium and vecuronium is lost after removal of one or both of the acetylcholine moieties. An analysis of the relationship between neuromuscular blocking dose and duration of action revealed that it was reciprocal, and it is suggested that a nondepolarizing equivalent of suxamethonium, when discovered, may necessarily be a drug of relatively low potency. PMID- 2898903 TI - Vecuronium inhibits histamine N-methyltransferase. AB - Although there have been clinical reports of significant hypotension and flushing associated with the use of vecuronium, it produces minimal cardiovascular effects in the vast majority of patients. In addition, there is no evidence that vecuronium stimulates the release of histamine. The authors performed in vitro kinetic studies to determine the effect of vecuronium on histamine N methyltransferase (HNMT), the primary catabolic enzyme for histamine in humans. They also examined plasma from patients who had received vecuronium (0.1 or 0.2 mg/kg) to determine whether clinically used concentrations of the drug could inhibit HNMT. It was determined that vecuronium is a strong inhibitor of HNMT; apparent Ki = 1 microM. The inhibition is competitive with respect to methyl donor and noncompetitive with respect to histamine. Vecuronium, in doses greater than or equal to 0.1 mg/kg, may delay the metabolism of histamine by HNMT in vitro. PMID- 2898904 TI - Importance of the level of paralysis recovery for a rapid antagonism of vecuronium with neostigmine in children during halothane anesthesia. PMID- 2898905 TI - Effect of terfenadine on the bronchoconstriction induced by ultrasonically nebulized distilled water. AB - Ultrasonically nebulized distilled water (UNDW) has been shown to induce bronchoconstriction in asthmatics. The proposed mechanism is through changes in osmolarity of the airway fluids and subsequent release of mediators from airway mast cells. We investigated whether terfenadine has a protective effect on UNDW challenges. Twelve mild-to-moderate asthmatics responded to screening a methacholine and UNDW challenge. For four hours after the ingestion of 0, 120, and 240 mg of terfenadine pulmonary responses were performed, followed by a UNDW challenge. Nine of 12 subjects dropped 20% after 120 mg and after 240 mg. There was a suggestion of a protective effect at 120 mg (P = .054), which was significant at 240 mg (P = .012) when the areas under the dose-response curves were compared. Bronchoconstriction induced by UNDW may in part be caused by histamine release and was attenuated by an oral antihistamine. PMID- 2898906 TI - A double-blind study of astemizole and terfenadine in the treatment of perennial rhinitis. PMID- 2898908 TI - Colocalization of VIP with other neuropeptides and neurotransmitters in the autonomic nervous system. PMID- 2898907 TI - Coronary artery disease, lipid disorders and genetic polymorphisms. AB - Coronary artery disease (CAD) is the leading cause of morbidity and mortality in most industrialized countries, accounting for one out of every two deaths in the United States. Disorders of the lipid transport system resulting from complex interactions among nutritional, environmental and genetic factors, play a very important role in the development of this disease. It has been proposed that low density lipoproteins (LDL) cause cholesterol deposition in the arterial wall, whereas high density lipoproteins (HDL) promote efflux of cholesterol from this site. Thus, low levels of HDL and/or high levels of LDL, have been associated with increased risk of CAD. Apolipoprotein A-I (Apo A-I) is the major protein component of HDL, and it has been proposed that the levels of this protein are a better predictor of risk of CAD than the level of cholesterol in HDL. The human Apo A-I gene has been characterized, and it has been found to be adjacent to the genes for apolipoproteins C-lll and A-lV on the long arm of chromosome 11. The cloning of these genes provides the appropriate tools to apply molecular genetic techniques to find differences between individuals at the gene level (restriction fragment length polymorphisms, RFLP) and to identify specific alleles at this particular gene locus which may be associated with a clinical phenotype, more specifically, premature CAD and familial hypoalphalipoproteinemia. In a preliminary study we have identified a Pst I restriction-endonuclease site flanking the human apolipoprotein A-I gene at its 3' end that is polymorphic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898910 TI - Role of vasoactive intestinal peptide and peptide histidine isoleucine in the cerebral circulation. PMID- 2898909 TI - Vasoactive intestinal peptide. Transmitter of inhibitory motor neurons of the gut. PMID- 2898911 TI - Neuroendocrine significance of vasoactive intestinal polypeptide. AB - The new data reported here, and available in the literature, are interpreted to indicate that acute release of PRL in stress is probably mediated by secretion of VIP and PHI arising from a subpopulation of paraventricular cells in the tuberoinfundibular system, and that this secretion is under serotonergic control, presumably by way of the raphe nuclear projection to the hypothalamus. The acute PRL response to suckling response is only partially under VIP/PHI control, and may be regulated by an as yet unidentified neural lobe hormone. In addition to the hypothalamic component of PRL regulation, there is a well-defined population of VIP cells within the pituitary, representing the only known example of VIP expression outside of nerve cells. This population of VIP cells is exquisitely responsive to thyroid status, and in common with the thyrotrope cell, is activated by hypothyroidism. Since VIP secretion is enhanced in the hypothyroid pituitary, and VIP release is stimulated by TRH, it is reasonable to postulate that paracrine VIP secretion may play a role in the reasonable to postulate that paracrine VIP secretion may play a role in the hyperprolactinemia prolactinemia that occurs in the hypothyroid human, although this is clearly not the case for the rat in whom hyperprolactinemia was not demonstrable. The role of VIP/PHI in human pituitary disease is unknown. We have been unable to identify any tumors that contain immunoreactive material using tissues prepared by standard methods. It may be that the demonstration of VIP/PHI is more demanding and will require better techniques for staining. The role of tuberoinfundibular VIP hypersecretion remains to be established but the evidence for stress-induced PRL hypersecretion in man encourages us to believe that at least some cases may be due to excessive hypothalamic activity. Additional potential neuroendocrine actions of VIP are in the secretomotor control of the ovary and thyroid, and in the regulation of somatostatin secretion and synthesis. In dispersed cell cultures (but not in whole hypothalamic slices from adult animals), VIP stimulates somatostatin secretion and independently stimulates the formation of somatostatin mRNA, an effect that can be duplicated in mixed cultures by treatment with forskolin, a postreceptor cAMP stimulator. In work carried out by Montminy and colleagues, the cAMP action has shown to be mediated by formation of a soluble protein that appears to activate the somatostatin gene promotor through interaction with a specific gene sequence. PMID- 2898912 TI - Vasoactive intestinal peptide in the lung. PMID- 2898914 TI - Dysfunction of the gastrointestinal tract. Vasoactive intestinal peptide in peristalsis and sphincter function. PMID- 2898913 TI - Somatostatin and analogues in the treatment of VIPoma. PMID- 2898915 TI - Antineoplastic activity of two taxol derivatives on an ovarian tumor xenografted into nude mice. AB - In order to compare the antineoplastic activities of taxol A, taxol B, a mixture of the two (taxol A 72%) and vinblastine, a human ovarian tumor serially transplanted into 104 female athymic mice was used. In the first experiment (11th passage), the antineoplastic activities of taxol A, taxol B and the mixture taxol AB were tested. The same dose was used in each case (12.5 mg/kg i.e. 1/20 of the evaluated LD50 value). It was administered subcutaneously for 5 consecutive days. Three courses of treatment were performed, with 2 rest periods of 1 week in between. All the taxol derivatives produced a statistically significant delay in the tumor growth. However, taxol B had the lowest chemotherapeutic response. In the second experiment (18th passage), different dose levels were administered (mixture 12.5 mg/kg/day x 4 - taxol A 8.8. mg/kg/day x 4 - taxol B 3.5 mg/kg/day x 4 - vinblastine 0.5 mg/kg/day x 2). For all the taxol derivatives 4 treatment courses with 3 rest periods of 4 days were used, and for vinblastine 4 treatment courses with 3 rest periods of 1 week. At the end of the second experiment, vinblastine, taxol A and a mixture of the two showed similar significant activity, whereas no objective antitumor response was observed following the taxol B treatment at the dose level chosen. The experimental results obtained clearly demonstrate that, in the taxane system, the greatest degree of antineoplastic activity can be attributed to taxol A. PMID- 2898916 TI - Antimigraine drug interactions with serotonin receptor subtypes in human brain. AB - The interactions of antimigraine agents with serotonin (5-hydroxytryptamine, 5 HT) receptor subtypes were analyzed in human frontal cortex membranes. The drugs studied included 5-HT antagonists, beta-adrenergic antagonists, and calcium channel blockers. At 5-HT1A sites labeled by 3H-8-hydroxy-2-(N,N-dipropylamino) tetralin, (-)pindolol, alprenolol, (-)propranolol, methysergide, cyproheptadine, and pizotifen are similar in that they display affinities of approximately 100 nM for this receptor. By contrast, only methysergide displays relatively high affinity (120 +/- 60 nM), whereas all other drugs have affinities greater than 1,000 nM for non-5-HT1A sites labeled by 3H-5-HT in human cortex. Finally, at 5 HT2 receptors labeled by 3H-spiperone, cyproheptadine, methysergide, and pizotifen are extremely potent agents (affinity constants of 1 to 10 nM), whereas amitriptyline (23 +/- 4 nM), verapamil (140 +/- 50 nM), and nifedipine (320 +/- 80 nM) are moderately potent. All other drugs are inactive at concentrations below 1,000 nM. These data demonstrate that most antimigraine drugs display high affinity for the 5-HT1A and/or 5-HT2 receptor subtypes in human brain. However, antimigraine efficacy cannot be explained by drug interactions with a single 5-HT receptor subtype. PMID- 2898917 TI - Abnormal physiology of the dorsal horn as related to the deafferentation syndrome. AB - The spinal cord dorsal horn has been implicated in the generation of pain and dysesthesias following nerve and nerve root damage and/or avulsion, as well as following damage in adjacent spinal cord regions. Alterations in the functional properties of dorsal horn neurons occur after deafferentation and may underlie the occurrence of abnormal sensations referred to the denervated body part. Abnormal activity following deafferentation has also been noted at thalamic and cortical levels. Some of these post-denervation functional changes, determined anatomically and/or electrophysiologically, are reviewed as well as the results of behavioral studies of the deafferentation syndrome in the rat. PMID- 2898918 TI - Neurochemistry of the dorsal horn. AB - The dorsal horn region of the spinal cord, particularly the dorsal root entry zone (DREZ), represents the first central integration center for nociceptive afferent impulses. Here, the excitatory neurotransmitters/modulators, products of the primary sensory neurons, are released, the segmental interneuronal influences pertain, and the descending bulbospinal tracts terminate. A vast variety of compounds are thus involved in the processing of nociceptive information in these areas, among which are the 'classical' neurotransmitters and the more recently described neuropeptides. A continued vast interest exists concerning the chemistry of the dorsal horn/DREZ region. The current developments and understanding regarding the pharmacology of this region are presented. Particular emphasis is given to the interactions among the various compounds, the coexistence of some of these within single neuronal populations, the importance of the opiate receptor subtypes, and the actions and localizations of some of the newly discovered neuropeptides. PMID- 2898919 TI - Growth of Clostridium perfringens in cooked chili during cooling. AB - U.S. Department of Agriculture regulations require that brick chili be cooled from 48.9 degrees C to 4.4 degrees C within 2 h of cooking, but processors may not always be able to comply. Studies were conducted to evaluate the extent of bacterial multiplication resulting from outgrowth of germinated Clostridium perfringens spores experimentally inoculated into chili and incubated at various temperatures. Inoculated samples were heated (75 degrees C for 20 min) to activate spores, quickly equilibrated, and held at one of five desired temperatures for 6 h. No growth was observed for C. perfringens in samples held at 26.7 degrees C and below for 6 h, but growth was observed by 6 h in samples held at 32.2 degrees C and after 2 h in samples held at temperatures between 37.8 degrees C and 48.9 degrees C. Using isothermal growth data, we developed a simple model for predicting the growth of bacteria with time under exponential cooling conditions. The model predicts both the lag phase and the numbers of bacteria at specific times during the growth phase. It was developed by using isothermal growth data and tested by using temperature-varying growth data from experiments with spores of C. perfringens in chili. Actual data agreed closely with predicted results. The results should be useful for evaluating the hazard potential for growth of C. perfringens in chili. PMID- 2898920 TI - [Therapeutic approach targeting the proteins involved in mechanisms of multidrug resistance]. AB - Recently, the mechanisms of multidrug resistance have been partly elucidated. Based on these resistant mechanisms, therapeutic approaches targeting the proteins involved in the mechanisms of multidrug resistance are under investigation. These include therapies with monoclonal antibodies, drug resistant genes and agents interacting with the proteins of resistant tumor cells. PMID- 2898921 TI - [Cancer-associated carbohydrate antigens available for serum diagnosis]. AB - Many of the recently developed tumor antigens detected by monoclonal antibodies are sugar chains and frequently associated with blood group substance. By immunohistological studies, we evaluated mainly the clinical usefulness and significance of the serum assay of CA-50 classified as a type 1 sugar chain, sialyl SSEA-1 classified as a type 2 sugar chain, and ST-439 with an undetermined structure, as well as their clinicopathological significance. In addition, the value of measurement of CA 19-9 and ST-439 in pancreatic juice was studied. The incidence of serum CA-50 was highest in pancreatic cancer (86%) and biliary tract cancer (66%), but relatively low in benign diseases. Moreover, the positivity and specificity of CA-50 as a tumor marker were no less useful than those of CA 19-9. However, comparison of serum levels of CA-50 with those of CA 19-9 in the same samples revealed a highly positive correlation in malignant diseases. Thus, improvement of the diagnostic rate through a combination assay of CA-50 and CA 19 9 seems unlikely. Both serodiagnostic and immunohistological studies showed that sialyl SSEA-1 and ST-439 were highly specific for tumor, whereas their appearances in serum or tumor were lower than CA 19-9 or CA-50 carrying the type 1 sugar chain. In addition, an appreciable number of sialyl SSEA-1 or ST-439 positive patients were found among those negative for CA 19-9 or CA-50. These results indicate that assay of sialyl SSEA-1 or ST-439 improves the diagnostic rate in combination with CA 19-9 or CA-50. Although the concentration of CA 19-9 in pancreatic juice from pancreatic cancer patients was highest, it was also significantly higher in patients with chronic pancreatitis than in controls. Furthermore, the overlap between the values in patients with cancer and those with chronic pancreatitis was great. On the other hand, the concentration of ST 439 in pancreatic juice was significantly higher only in patients with pancreatic cancer. These results indicate that the measurement of ST-439 in pancreatic juice is more useful as a tumor marker than measurement of CA 19-9, and that moreover, the assay of CA 19-9 in pancreatic juice could be used as a sensitive marker for nonspecific pancreatic injury. PMID- 2898923 TI - Clinical diagnosis of cryptorchidism. John Radcliffe Hospital Cryptorchidism Study Group. AB - We examined 3534 boys for cryptorchidism at birth, and, if present, again at 3 months of age. We compared Scorer's standard criterion for cryptorchidism, based on measurement of the testis from the public tubercle, with the simpler criterion of whether the testis was in the normal position, well down in the scrotum. At birth 210 (5.9%) boys were cryptorchid by measurement and 220 (6.2%) by position. By 3 months of age the cryptorchidism rate was identical (1.6%) whichever criterion was used. We therefore recommend that position be used as the sole criterion for diagnosing cryptorchidism. There was a clear decrease in the cryptorchidism rate with increasing birth weight. A testis that was undescended at birth was more likely to descend spontaneously by 3 months the lower its position along the normal pathway of descent. For a given position of the testis, cryptorchid babies weighing less than 2500 g had a greater chance of spontaneous descent by 3 months than larger babies. An independent effect of gestation is suggested; cryptorchid babies of less than 37 weeks' gestation were more likely to have normally descended testes at 3 months than babies of longer gestation. PMID- 2898922 TI - Possible association between breast cancer and malignant melanoma. PMID- 2898924 TI - Growth hormone releasing hormone or growth hormone treatment in growth hormone insufficiency? AB - Sixteen prepubertal children who were insufficient for growth hormone were treated with growth hormone releasing hormone (GHRH) 1-40 and GHRH 1-29 for a mean time of nine months (range 6-12 months) with each peptide. Eleven children received GHRH 1-40 in four subcutaneous nocturnal pulses (dose 4-8 micrograms/kg/day) and eight (three of whom were also treated with GHRH 1-40) received GHRH 1-29 twice daily (dose 8-16 micrograms/kg/day). Altogether 73% of the children receiving GHRH 1-40 and 63% receiving GHRH 1-29 showed a growth response. Double the daily dose of GHRH 1-29 was required to obtain equivalent growth response to pulsatile GHRH 1-40. A significant linear correlation was shown between growth hormone secretion and height velocity on GHRH 1-40 but not on GHRH 1-29 and there was a significant correlation between plasma GHRH and serum growth hormone concentrations during GHRH 1-40 administration. Response to conventional growth hormone treatment in a matched group of children was significantly better than the response after GHRH. A significant improvement in height velocity was observed in the children transferred to growth hormone replacement. Growth hormone remains the treatment of choice in growth hormone insufficiency. GHRH treatment may be of benefit in children with less severe growth hormone insufficiency in the presence of pulsatile endogenous growth hormone secretion. PMID- 2898925 TI - Acute confusional state and hyponatraemia due to inappropriate antidiuretic hormone secretion in polyarteritis nodosa. AB - An acute confusional state, which developed in a patient with polyarteritis nodosa (PAN), proved to be secondary to inappropriate secretion of antidiuretic hormone and consequent hyponatraemia. This is a very unusual complication of PAN and may well reflect a direct stimulation of the supraoptic nuclei owing to cerebral vasculitis. PMID- 2898926 TI - [Sequential development of vitamin D metabolites under isoniazid and rifampicin therapy]. AB - A sequential study of 25-hydroxy vitamin D (25-OH-D), 1.25 dihydroxy vitamin D [1.25 (OH)2-D], PTH, alkaline phosphatase and gammaglutamyl transpeptidase (gamma GT) was undertaken in a series of 46 children with asymptomatic tuberculosis treated by isoniazid (INH) alone or associated with rifampin (RMP). These parameters were measured before treatment, 1 month, 3 months after the onset and at the end of treatment (6 months). In order to reduce the influence of the time of the year on the 25-OH-D levels, 22 patients were selected for whom the whole treatment took place between October and May of the following year. In this group, 13 children were treated by INH and RMP, 9 by INH alone. A statistically significant decrease in 25-OH-D levels could be demonstrated after 3 months of treatment in 13 patients under INH and RMP as well as a significant increase in alkaline phosphatase and gamma GT levels. In 9 patients given INH alone, 1.25 (OH)2-D levels decreased after 3 months without significant changes in 25-OH-D, alkaline phosphatase or gamma GT levels. These results emphasize the need for regular biochemical supervision, even if no sign of rickets is observed in these patients. PMID- 2898927 TI - [Flumazenil: a useful antagonist in pediatrics]. PMID- 2898928 TI - [Growth of children treated for leukemia or malignant lymphoma. Influence of cranial radiotherapy]. AB - We studied the height growth of 96 children presenting with acute leukemia or non Hodgkin lymphoma, together with an investigation of GH and TSH in 41 of them. There were 2 groups: group I consisting of 19 patients without brain irradiation and group II consisting of 77 patients with prophylactic brain irradiation. Initial average height was identical in both groups. Growth rate was significantly decreased in group II but not in group I (p less than 0.01). There is a correlation between the decrease of growth rate and the decrease of GH to arginine stimulation test (p less than 0.03). A lack of response to GRF-44 was noted in 4 of 11 investigated patients. TSH and prolactin secretions were unchanged. PMID- 2898929 TI - Enzyme immuno assay for the detection of virus specific IgG and IgM antibody in patients with haemorrhagic fever with renal syndrome. AB - Consecutive serum samples collected from 235 patients with Haemorrhagic Fever with Renal Syndrome (HFRS), between two days and two years after onset of disease, have been analysed for the presence of IgG and IgM type of antibodies specific for Hanta-viruses. The sera were screened in parallel by a newly developed indirect Immuno Enzyme Assay (EIA) in parallel with Indirect Immunofluorescent Antibody Assay (IFA). In both tests the Hantaan virus strain 76 118 was used as the antigen. The EIA was much more sensitive than the IFA test for the detection of IgM type antibodies. With the indirect EIA IgM type antibodies against Hantaan virus 76-118 have been detected in HFRS patient's sera from the second day of illness indicating the usefulness of this test for the early serological diagnosis of this disease. PMID- 2898930 TI - Introduction of foreign strains of Suid herpesvirus 1 (Aujeszky's disease virus) documented by restriction fragment pattern (RFP) analysis. AB - Six isolates of Suid herpesvirus 1 (SHV-1) collected from clinical outbreaks of Aujeszky's disease (AD) in Jutland in January-February, 1985, were compared by restriction fragment pattern (RFP) analyses with older SHV-1 isolates from Jutland as well as with SHV-1 isolates from different parts of West Germany and Ireland. The RFP analysis indicated that the outbreaks were caused by SHV-1 isolates introduced from abroad. PMID- 2898931 TI - Comparison of a cheetah herpesvirus isolate to feline herpesvirus type 1. AB - A cytopathogenic virus with size and structural characteristics of a Herpesviridae was isolated from a cheetah with severe ulcerative dermatitis. Restriction endonuclease analysis and cross-hybridization studies revealed that the isolate was related to feline herpesvirus type 1 (FHV-1). Antigenic comparison studies using anti-FHV-1 serum demonstrated the presence of common antigens in the FHV-1 and the isolate from the cheetah. PMID- 2898932 TI - Topical beta-blocker therapy and central nervous system side effects. A preliminary study comparing betaxolol and timolol. AB - Topical beta-blocking agents have been associated with adverse central nervous system (CNS) effects, including depression, emotional lability, and sexual dysfunction. Two studies were done to determine if patients who develop CNS effects while using timolol maleate would improve with betaxolol hydrochloride. In one study, 18 patients with CNS symptoms during timolol therapy were switched to betaxolol. Sixteen of the 18 patients noted symptomatic improvement with betaxolol. The second study involved seven patients with CNS symptoms during timolol therapy who were entered into a double-masked cross-over study. In two patients CNS symptoms resolved with betaxolol; in three patients symptoms improved; and in one patient symptoms worsened with betaxolol. Although factors influencing beta-blocker activity in the CNS are not well understood, there may be some advantage to a selective agent. PMID- 2898933 TI - Postjunctional alpha 2-adrenoceptors in blood vessels of human nasal mucosa. AB - Human nasal mucosa has various types of blood vessels and is a good tissue for demonstrating receptors for many vasoactive substances, including alpha adrenoceptors. In contrast to the large contractile response induced by alpha 1 agonists, our studies have shown that alpha 2-agonists produce a small maximal contraction. This alpha 2-induced response was easily blocked by alpha 1 antagonists, indicating that it is evoked, at least partially, by the stimulation of alpha 1-adrenoceptors. Noradrenaline (NA)-induced contractions could not be abolished by either alpha 1- or alpha 2-antagonists alone, but were almost completely blocked by the combination of both antagonists. This suggests the presence of postjunctional alpha 2-adrenoceptors. The low-maximal responsiveness to alpha 2-agonists and calcium independency of NA-induced contractions were distinct from our former results obtained on canine nasal specimens. PMID- 2898934 TI - Human gut neuroanatomy: methodology for a quantitative analysis of nerve elements and neurotransmitter diversity in the human "enteric nervous system". AB - After a few decad of neglect, the "enteric nervous system" has recently regained the attention of investigators. Indeed, various studies, such as those which led to the isolation from the gut of a number of neuropeptides, subsequently demonstrated throughout the nervous system, have prompted major advancements of modern neuroscience. In spite of a wealth of animal investigations and a number of human studies, however, available information concerning the human "enteric nervous system" is comparatively sparse. In the opinion that such lack of information was largely due to unavailability of appropriate techniques, we have initiated and developed a new comprehensive methodology. This way, a quantitative analysis was made possible of both nerve structure and transmitter status, point to-point along the gut, as well as within the various, functionally heterogeneous components of the gastrointestinal wall itself. After a general introduction, the present review is intended to summarize such methodology, with the addition of a few illustrative examples of application and a practically-oriented guideline to its use, in the form of technical appendix. PMID- 2898935 TI - Medullary and mesencephalic neuronal groups reacting to antibodies against VIP, somatostatin and bombesin in adult Gallus gallus domesticus. AB - The caudo-cranially intermediate one-third of medullary dorsal region, the periaqueductal grey and the rostro-ventral portion of the midbrain tegmentum of adult chickens were studied in detail by means of the PAP-DAB procedure, to define further the main morphological features of the neuronal populations that in previous studies had shown VIP (Vasoactive Intestinal Polypeptide), Somatostatin (SRIF)-, and Bombesin-like immunoreactivities. In the medulla, VIP like immunoreactivity was detected within neuronal bodies and processes and extended down to the cervical spinal cord. SRIF-like immunoreactivity was seen only within nerve cell processes, at least a part of which could be sensitive fibre terminals. Bombesin-like immunoreactivity was observed only within neuronal processes. In the periaqueductal grey, all 3 immunoreactivities were detected within perikarya and neuronal processes, with a higher density cranially. In the rostro-ventral portion of the midbrain tegmentum, VIP-like and Bombesin-like immunoreactivities were detected (the latter being located somewhat more cranially) both in neuronal bodies and in processes. SRIF-like immunoreactivity was found in this region only in long neuronal processes. PMID- 2898936 TI - Kinetic studies of chicken and turkey liver mitochondrial aspartate aminotransferase. AB - The kinetic behaviour of chicken liver and turkey liver aspartate aminotransferases (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) was studied. Steady-state data were obtained from a wide range of concentrations of substrates and product L-glutamate. The data were fitted by rational functions of degree 1:1, 1:2 and 2:2 with respect to substrates and 0:1, 1:1, 0:2 and 1:2 with regard to product (L-glutamate), by using a non-linear regression program that guarantees the fit. The goodness of fit was improved by the use of a computer program that combines model discrimination parameter refinement and sequential experimental design. It was concluded that aspartate aminotransferase requires a minimum velocity equation of degree 2:2 for L-aspartate, 2:2 for 2-oxoglutarate and 1:2 for L-glutamate. Finally, a plausible kinetic mechanism that justifies these experimental results is proposed. PMID- 2898937 TI - Affinity purification and biochemical characterization of histolysin, the major cysteine proteinase of Entamoeba histolytica. AB - We report a one-step method for the purification to homogeneity of a cysteine proteinase of Entamoeba histolytica (histolysin) by affinity chromatography of the soluble extract of the parasite on immobilized phenylalanyl(2 phenyl)aminoacetaldehyde semicarbazone. The enzyme has an apparent Mr of 26,000 by SDS/polyacrylamide-gel electrophoresis and 29,000 by gel chromatography. Its pH optimum varies widely, from 5.5 with azocasein to approx. 7 with other protein substrates and benzyloxycarbonylphenylalanyl-L-citrullylaminomethylcourmarin++ + (Z-Phe-Cit-NHMec), and to 9.5 with benzyloxycarbonylphenylalanylarginylaminomethylcoumarin (Z-Phe-Arg-NHMec) and benzyloxycarbonylarginylarginylaminomethylcourmarin (Z-Arg-Arg-NHMec). Values of Km, kcat. and kcat/Km are 1.5 microM, 130 s-1 and 87 X 10(6) M-1.s-1 for Z-Arg Arg-NHMec, and 32 microM, 0.4 s-1 and 0.012 x 10(6) M-1.s-1 for Z-Phe-Arg-NHMec, respectively, at pH 7.5 and 37 degrees C. The enzyme is inhibited by leupeptin and such inhibitors of cysteine proteinases as L-transepoxysuccinyl-L-leucylamido 4-(guanidino)butane, peptidyldiazomethanes, iodoacetic acid and chicken cystatin. The tentative N-terminal amino acid sequence of the enzyme closely resembles that of papain. Histolysin does not degrade type I collagen or elastin, but it is active against cartilage proteoglycan and kidney glomerular basement-membrane collagen. It also detaches cells from their substratum in vitro, and could well play a role in tissue invasion. PMID- 2898938 TI - Homoeostatic control of membrane cholesterol and fatty acid metabolism in the rat liver. AB - Experiments were designed to assess the effect of cholesterol feeding, with or without high levels of either saturated (coconut oil) or unsaturated (sunflower seed oil) fat on the fatty acid composition of hepatic microsomal membrane lipids, as well as on the activities of several membrane-bound enzymes of cholesterol synthesis and metabolism. Administration of 2% (w/w) cholesterol in the rat diet inhibited hydroxymethylglutaryl-CoA reductase activity, and this inhibition was much more pronounced when cholesterol was fed in combination with unsaturated rather than with saturated fat. Cholesterol 7 alpha-hydroxylase activity was increased by all the high-cholesterol diets and inhibited by both the high-fat diets. Cholesterol esterification, as assessed by acyl CoA:cholesterol acyltransferase (ACAT) activity, was enhanced after unsaturated fat feeding. Cholesterol supplement, without any added fat, failed to elicit any significant increase in ACAT activity, whereas consumption of cholesterol in combination with unsaturated fat led to the greatest increase in ACAT activity. After cholesterol feeding, C18:1 and C18:2 fatty acids in the microsomal phospholipids were increased, with concomitant decreases in C18:0, C20:4 and C22:6 fatty acids, leading to an overall decrease in membrane unsaturation, irrespective of the particular fat supplement. It can be concluded that the inhibition of cholesterol biosynthesis and the enhancement of cholesterol utilization, either by increased bile formation or by increased cholesterol esterification, after cholesterol feeding, may not be enough to prevent cholesterol accumulation in the microsomal membranes. Then, to compensate for the altered fluidity resulting from cholesterol enrichment, the unsaturation of membrane phospholipids is decreased, which would in turn have an effect on membrane lipid fluidity opposite to that of increased cholesterol. PMID- 2898939 TI - The induction, desensitization and de-induction of tyrosine aminotransferase by 8 bromo-cyclic AMP in rat hepatoma cells. AB - Addition of 1-3 mM-8-bromo-cyclic AMP to monolayer cultures of H-4 rat hepatoma cells resulted in a rapid but short-lived increase in tyrosine aminotransferase (EC 2.6.1.5) activity. The transient nature of this induction is due to desensitization to 8-bromo-cyclic AMP. Throughout this time course of induction and desensitization, removal of 8-bromo-cyclic AMP resulted in a rapid and significant decrease in tyrosine aminotransferase activity, a process referred to as 'de-induction' in this study. We showed that the changes in tyrosine aminotransferase activity in its induction, desensitization and de-induction by 8 bromo-cyclic AMP were directly attributable to changes in the synthesis rate of the protein, and the amount of translatable and hybridizable mRNA encoding for tyrosine aminotransferase (mRNATAT). We further showed that this desensitization was specific to cyclic AMP. First, only active analogues of cyclic AMP and agents which increased cellular concentrations of cyclic AMP elicited this desensitization. Second, the desensitized cells were refractory only to the effects of 8-bromo-cyclic AMP; dexamethasone and insulin induced the tyrosine aminotransferase activity in the 8-bromo-cyclic AMP-desensitized cells in a manner similar to that of the controls. Studies on the metabolism of 8-bromo cyclic AMP suggest that neither its degradation nor the accumulation of its primary metabolite, 8-bromoadenosine, played a significant role in modulating the expression of tyrosine aminotransferase during the time course of action of 8 bromo-cyclic AMP. These results provide evidence for a specific pretranslational mode of action of cyclic AMP in the control of tyrosine aminotransferase expression in its desensitization and de-induction, in addition to the early phase of induction. PMID- 2898940 TI - Characterization of atrial-natriuretic-factor-receptor-coupled membrane guanylate cyclase from rat and mouse testes. AB - Studies with isolated adrenal cells and mouse testicular cells have supported a mediatory role of cyclic GMP in ANF (atrial natriuretic factor)-dependent steroidogenic signal transduction. This concept has been strengthened by the purification and biochemical characterization of a 180 kDa protein, which appears to contain both ANF receptor and guanylate cyclase activities, from rat adrenocortical carcinoma cells. Utilizing the antibody to 180 kDa membrane guanylate cyclase as a probe, we now demonstrate the direct presence of ANF dependent membrane guanylate cyclase in mouse and rat testes. The antibody blocks the ANF-dependent guanylate cyclase activity in isolated membranes, and Western blot analysis of the partially purified enzyme reveals a single 180 kDa protein. The presence of this enzyme in mouse and rat testes, together with its previous demonstration in rat adrenocortical carcinoma, represent an important potential biochemical role for this enzyme in receptor-mediated steroidogenic signal transduction. PMID- 2898941 TI - Effects of indole alkaloids on multidrug resistance and labeling of P glycoprotein by a photoaffinity analog of vinblastine. AB - Multidrug resistant cells are characterized by decreased drug accumulation and retention, thought to be mediated by a high molecular weight glycoprotein, P glycoprotein (P-gp). Agents such as verapamil have been shown to increase anticancer drug cytotoxicity and increase the amount of drug accumulated and retained by such cells. We show here that in addition to verapamil, reserpine, chloroquine, quinine, quinacrine, yohimbine, vindoline, and catharanthine also enhance the cytotoxicity of vinblastine (VLB) in a multidrug resistant, human leukemic cell line, CEM/VLB1K, described here for the first time. These cells express P-gp as a doublet that is photoaffinity labeled by the analog of VLB, N(p azido-[3-125I]salicyl)-N'-beta-aminoethylvindesine ([125I]NASV). Both reserpine and, to a lesser extent, verapamil, compete with [125I]NASV for binding to P-gp. We also found that chloroquine, quinacrine, vindoline, and catharanthine, each of which enhanced VLB cytotoxicity in CEM/VLB1K cells by 10- to 15-fold, similarly inhibited [125I]NASV labeling of P-gp. However, neither quinine nor yohimbine inhibited this labeling, and the inhibition produced by catharanthine and vindoline was the greatest or exclusively on the lower band of the P-gp doublet. Our results suggest a complex relationship between the ability of a compound to modulate MDR and its ability to compete for binding to P-gp. PMID- 2898942 TI - Selective incorporation of n-3 and n-6 fatty acids in essential fatty acid deficient rats in response to short-term oil feeding. AB - Essential fatty acid deficient male Sprague Dawley rats were fed for 7 days a fat free semi-synthetic diet supplemented with 10% by weight of different oil supplements. The oil supplement was a mixture of olive, safflower and linseed oils prepared at different proportions so the dietary n-9/n-6/n-3 ratios were approximate 2/1/1, 1/2/1, 1/1/2, and 1/1/1. The fatty acid compositions of plasma and liver lipids were then examined. Our results show polyunsaturated n-6 and n-3 fatty acids were selectively incorporated into plasma and liver phospholipids, and also into plasma cholesteryl esters. A preferential incorporation of n-6 over n-3 fatty acids into plasma cholesteryl esters and phospholipids was also observed. PMID- 2898943 TI - Increase of daunorubicin and vincristine accumulation in multidrug resistant human ovarian carcinoma cells by a monoclonal antibody reacting with P glycoprotein. AB - An overexpression of plasma membrane 170-180 kDa P-glycoproteins is consistently found in multidrug-resistant (MDR) cell lines. In this study MRK-16, a monoclonal antibody (mAb) reacting with P-glycoprotein is used to study the putative functional role of this protein in vincristine (VCR) and daunorubicin (DNR) cellular accumulation in the MDR human ovarian carcinoma cell line 2780AD. We established that this cell line is highly cross-resistant to vincristine and daunomycin, related to a greatly reduced drug accumulation. Verapamil (Vp) (8 microM) caused a 3.6-fold increase in DNR as well as VCR accumulation. Exposition of 2780AD cells to MRK-16 led to an increase of 30% in cellular accumulation of VCR, both in normal growth medium as well as in medium without added glucose and with sodium azide, which largely depleted cellular ATP levels. No increase in DNR accumulation was found under these conditions. However, in the presence of 8 microM Vp, MRK-16 increased not only VCR but also DNR accumulation with about 30%. The relative increase of DNR accumulation was constant in a concentration range of 0.2-4 microM DNR. These data indicate that mAbs against P-glycoprotein might potentiate the action of calcium antagonists like Vp to increase cellular anthracycline accumulation. PMID- 2898944 TI - N-alkyl colchiceineamides: their inhibition of GTP or taxol-induced assembly of tubulin. PMID- 2898945 TI - Serum biochemical and haematological markers of alcohol abuse in patients with femoral neck and intertrochanteric fractures. AB - Excessive alcohol intake causes bone loss. Alcohol abuse is a commonly associated disorder in femoral neck fractures in men, but little attention is given to such an association in women. Using serum biochemical and haematological markers (mean red cell volume MCV, gamma-glutamyl transpeptidase GGT, aspartate transaminase AST, uric acid UA and triglyceride TG) alcohol abuse was assessed in 14 men and 93 women with non-violent fractures of the hip. Abnormal elevations in one or more of the five test pairs known to correlate with increasing alcohol consumption (GGT/MCV, GGT/AST, AST/MCV, MCV/UA) were found in 7.1% of men, and 11.8% of women. When abnormal results in other test pairs were included the prevalence rose to 14.3% in men and 20.4% in women. These figures are higher than those reported for the general population of elderly people. PMID- 2898946 TI - [Formation of a multicenter study conducted during the 1986 pollen season]. AB - A multicentre study was conducted in France during the 1986 pollen season. 186 patients who were diagnosed as suffering from allergic rhinitis (seasonal and perennial) were admitted to the trial. The treatment that was administered was: RHINAAXIA, nasal solution, applied as a double spray in each nostril, five times daily during one or two months. On the 14th day, at the first assessment, the treatment was found to have been effective or very effective (63.3% of physicians). This good result was confirmed by the later evaluations (67.8% on day 30 and 69.9% on day 60). The diary cards showed that patients who had severe symptoms at the start were greatly improved (2/3 in 4 days). In addition, good tolerance of RHINAAXIA is confirmed in this study and makes it the treatment of choice for allergic rhinitis. PMID- 2898948 TI - Structure and chromosomal localization of the human renal kallikrein gene. AB - Glandular kallikreins are a family of proteases encoded by a variable number of genes in different mammalian species. In all species examined, however, one particular kallikrein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. This kallikrein is found in the kidney, pancreas, and salivary gland, showing a unique pattern of tissue-specific expression relative to other members of the family. We have isolated a genomic clone carrying the human renal kallikrein gene and compared the nucleotide sequence of its promoter region with those of the mouse renal kallikrein gene and another mouse kallikrein gene expressed in a distinct cell type. We find four sequence elements conserved between renal kallikrein genes from the two species. We have also shown that the human gene is localized to 19q13, a position analogous to that of the kallikrein gene family on mouse chromosome 7. PMID- 2898949 TI - 1H Fourier transform NMR studies of insulin: coordination of Ca2+ to the Glu(B13) site drives hexamer assembly and induces a conformation change. AB - 1H Fourier transform NMR investigations of metal ion binding to insulin in 2H2O were undertaken as a function of pH* to determine the effects of metal ion coordination to the Glu(B13) site on the assembly and structure of the insulin hexamer. The C-2 histidyl regions of the 1H NMR spectra of insulin species containing respectively one Ca2+ and two Zn2+/hexamer and three Cd2+/hexamer have been assigned. Both the Cd2+ derivative (In)6(Cd2+)2Cd2+, where two of the Cd2+ ions are coordinated to the His(B10) sites and the remaining Cd2+ ion is coordinated to the Glu(B13) site [Sudmeier, J.L., Bell, S.J., Storm, M. C., & Dunn, M.F. (1981) Science (Washington, D.C.) 212, 560], and the Zn2+-Ca2+ derivative (In)6-(Zn2+)2Ca2+, where the two Zn2+ ions are coordinated to the His(B10) sites and Ca2+ ion is coordinated to the Glu(B13) site, give spectra in which the C-2 proton resonances of His(B10) are shifted upfield relative to metal free insulin. Spectra of insulin solutions (3-20 mg/mL) containing a ratio of In:Zn2+ = 6:2 in the pH* region from 8.6 to 10 were found to contain signals both from metal-free insulin species and from the 2Zn-insulin hexamer, (In)6(Zn2+)2. The addition of either Ca2+ (in the ratio In:Zn2+:Ca2+ = 6:2:1) or 40 mM NaSCN was found to provide sufficient additional thermodynamic drive to bring about the nearly complete assembly of insulin hexamers. Cd2+ in the ratio In:Cd2+ = 6:3 also drives hexamer assembly to completion. We postulate that the additional thermodynamic drive provide by Ca2+ and CD2+ is due to coordination of these metal ions to the Glu(B13) carboxylates of the hexamer. At high pH*, this coordination neutralizes the repulsive Coulombic interactions between the six Glu(B13) carboxylates and forms metal ion "cross-links" across the dimer-dimer interfaces. Comparison of the aromatic regions of the 1H NMR spectra for (In)6(Zn2+)2 with (In)6(Zn2+)2Ca2+, (In)6(Cd2+)2Cd2+, and (In)6(Cd2+)2Ca2+ indicates that binding of either Ca2+ or Cd2+ to the Glu(B13) site induces a conformation change that perturbs the environments of the side chains of several of the aromatic residues in the insulin structure. Since these residues lie on the monomer-monomer and dimer-dimer subunit interfaces, we conclude that the conformation change includes small changes in the subunit interfaces that alter the microenvironments of the aromatic rings. PMID- 2898947 TI - Changes in postprandial release patterns of gastrointestinal hormones in late pregnancy and the early postpartum period. AB - Intestinal transit time increases and gastrointestinal incretin effect is reported to decrease in pregnancy. The release patterns of gastrointestinal hormones related to these functions were studied in eight women before and after ingestion of a standardized meal at 32-34 weeks gestation and at 4 days postpartum. Basal plasma motilin and the integrated meal response of motilin, pancreatic polypeptide (PP) and gastric inhibitory polypeptide (GIP) were significantly lower in pregnancy than postpartum. The meal-induced rise of somatostatin and vasoactive intestinal polypeptide (VIP) was, however, absent in late pregnancy; whereas the somatostatin response recovered postpartum, and the plasma VIP concentrations stabilized at significantly higher levels postpartum without any meal response. Basal and meal-induced plasma insulin were significantly higher in pregnancy. PMID- 2898950 TI - The rotation of the alpha subunit of F1 relative to minor subunits is not involved in ATP synthesis. Evidence given by using an anti-alpha subunit monoclonal antibody. AB - To test whether ATP synthesis could occur via a mechanism of rotational catalysis in which the alpha and beta subunits of F1 would rotate with respect to the minor subunits, we have measured the rate of ATp synthesis after binding various masses of antibodies to F1. If the rotation was an essential feature of the mechanism, the rate of ATP synthesis should be inhibited either completely or proportionately to the load carried by F1. Bivalent immunoglobulins (IgG) or monovalent Fab fragments of an anti-alpha monoclonal antibody (7B3) were bound to F1 present in electron-transport particles in a ratio of 2 Fab or 2 IgG per F1. This binding similarly inhibited the rate of ATP synthesis by a maximum of about 50%. When anti-mouse immunoglobulins were added to the F1-7B3 (IgG) complex, no significant change in the rate of inhibition was observed. In conclusion, the rate of ATP synthesis was the same when F1 was loaded with 100 kDa (2 Fab), 300 kDa (2 IgG, 7B3) or 900 kDa (2 IgG + 4 ant-mouse IgG). It is concluded that the rotation of the alpha subunits is extremely unlikely to play an essential role in the mechanism of ATP synthesis. PMID- 2898951 TI - [Characteristics of K+ uptake in S. enteritidis bacteria]. AB - Bacterial Salmonella enteritidis var. Issatchenko in media without exogenic energy source uptakes K+ in one step with Km 2.1 mM and Vmax 0.08 mM min-1/10(12) cells. This K+ uptake does not depend on pH and osmotic shock and is not inhibited by DCC. Endogenic energy source (glucose) leads to K+ uptake with Km 2.8 mM and Vmax 0.10 mM min-1/10(12) cells, and secretion of H+. The ratio of the DCC-sensitive fluxes of H+ to K+ equals 2. Arsenate and protonophores depress the K+ uptake. Valinomycin decreases the rate of K+ uptake. It is assumed that K+ uptake takes place via the Trk-like system, which works as a separate system as supercomplex with the H+-ATPase complex. PMID- 2898952 TI - [Effects of cordanum and propranolol on coronary resistance]. AB - The effects of cordanum and propranolol on the coronary resistance were studied in isolated cat hearts. The infusion of cordanum and propranolol may be followed by both reduction or enlargement of the coronary resistance. The alterations of the coronary resistance are in most cases parallel with the weakening of the isolated heart function. In some cases cordanum infusion is followed by a short term reduction in the coronary resistance, which precedes the alteration of the heart function and thus may be due to direct cordanum effect on the coronary vessels. PMID- 2898953 TI - Molecular genetic analysis of porcine von Willebrand disease: tight linkage to the von Willebrand factor locus. AB - von Willebrand disease (vWD), one of the most common bleeding disorders in humans, is manifested as a quantitative or qualitative defect in von Willebrand factor (vWF), an adhesive glycoprotein (GP) with critical hemostatic functions. Except for the rare severely affected patient with a gene deletion as etiology of the disease, the molecular basis for vWD is not known. We studied the molecular basis for vWD in a breeding colony of pigs with a disease closely resembling the human disorder. The porcine vWF gene is similar in size and complexity to its human counterpart, and no gross gene deletion or rearrangement was evident as the pathogenesis of porcine vWD. A restriction fragment-length polymorphism (RFLP) within the porcine vWF gene was identified with the restriction endonuclease HindIII, and 22/35 members of the pedigree were analyzed for the polymorphic site. Linkage between the vWF locus and the vWD phenotype was established with a calculated LOD score of 5.3 (1/200,000 probability by chance alone), with no crossovers identified. These findings indicate that porcine vWD is due to a molecular defect within (or near) the vWF locus, most likely representing a point mutation or small insertion/deletion within the vWF gene. PMID- 2898954 TI - A second BamHI DNA polymorphism and haplotype association in the factor IX gene. AB - A second BamHI DNA polymorphism has been identified in the factor IX gene in an American black population at an allelic frequency of 0.13. This site has been localized within 500 basepairs (bp) 5' to the XmnI intron 3 polymorphic site and increases the heterozygosity of black females at the factor IX gene locus. In addition, haplotype analysis of factor IX genes at five polymorphic loci indicates that although there is conservation of sequences between the races, factor IX genes show more heterogeneity in an American black population and thus more heterozygosity is observed in black females compared with whites. This increased heterogeneity is due to DNA polymorphisms unique to black populations and to linkage equilibrium between the most 5' and 3' polymorphic sites in factor IX genes in blacks. PMID- 2898955 TI - Beta thalassemia in Melanesia: association with malaria and characterization of a common variant (IVS-1 nt 5 G----C). AB - Data on the distribution of beta thalassemia among over 6,000 Melanesians reveals a major difference in the carrier rates between populations in the malarious coastal regions of New Guinea and those living in the historically malaria-free Highlands. The island of Maewo in Vanuatu has a particularly high incidence of beta + thalassemia associated with a single restriction enzyme haplotype. Direct cloning into a plasmid vector and sequence analysis demonstrate that the mutation is a G to C transversion at position 5 of intron 1 of the beta-globin gene. Oligonucleotide probe surveys indicate that this variant accounted for all cases of beta thalassemia studied from Maewo. It is also common in coastal Papua New Guinea where haplotype and oligonucleotide probe data suggest that the molecular basis of beta thalassmia is more heterogeneous. PMID- 2898956 TI - Differential effects of beta-endorphin fragments on human natural killing. AB - The endogenous opiate peptide, beta-endorphin, has two effects on human natural killing (NK). Preincubation of effector lymphocytes with between 10(-7) and 10( 11) M beta-endorphin increases NK. Preincubation with lower concentrations results in a reduction in NK. Endorphin peptides containing an unmodified N terminal sequence, and which are known to bind only to opiate receptors, increase NK. Sequences reported to bind only to nonopiate receptors reduce NK. PMID- 2898957 TI - Effect of artificial respiratory volume on the cardiovascular responses to an alpha 1- and an alpha 2-adrenoceptor agonist in the air-ventilated pithed rat. AB - 1. The effect of varying artificial respiratory volume (at a fixed rate of 54 min 1) on cardiac output, its distribution and tissue blood flows were determined with tracer microspheres in control pithed rats or during pressor responses to either the alpha 1-adrenoceptor agonist phenylephrine or the alpha 2-agonist xylazine. Phenylephrine was investigated in the presence of propranolol (3 mg kg 1). The rats were pithed under halothane anaesthesia. 2. A respiratory volume of 15 ml kg-1 produced modest hypercapnia (PaCO2 = 47 mmHg), hypoxia (PaO2 = 60 mmHg) and acidosis (pH = 7.35) relative to control animals respired at 20 ml kg-1 (PaCO2 = 32 mmHg; PaO2 = 77 mmHg; pH = 7.47). In rats respired at 15 ml kg-1, total peripheral resistance was lower, and cardiac output greater (due to increased stroke volume), than in the controls. Lowering respiratory volume reduced distribution of cardiac output to the kidneys, increased it to the large intestine and also increased blood flow through the gastrointestinal tract, skin and spleen. A respiratory volume of 30 ml kg-1 gave mild hypocapnia (PaCO2 = 19 mmHg), hyperoxia (PaO2 = 101 mmHg) and alkalosis (pH = 7.59) compared to 20 ml kg 1 but had no effect on cardiac output distribution or organ blood flow although heart rate was 29% greater at 30 ml kg-1. 3. Xylazine (500 micrograms bolus followed by 100 micrograms min-1 infusion) at all three respiratory volumes gave well-sustained mean pressor responses of 62-64 mmHg by increasing both total peripheral resistance and cardiac output (resulting from increased stroke volume). It increased the proportion of cardiac output passing to the liver, reduced that going to the spleen and gastrointestinal tract and increased cardiac, renal and hepatosplanchnic blood flows. 4. The secondary, relatively sustained, pressor effect of phenylephrine (5 micrograms bolus followed by 0.4 micrograms min-1 infusion, i.v.) varied at the 3 respiratory volumes with mean values from 32 to 53 mmHg. This response was due to both increased total peripheral resistance and cardiac output (resulting from greater stroke volumes and/or heart rates). Phenylephrine increased the proportion of cardiac output passing to the gastrointestinal tract, heart, kidneys and hepatosplanchnic bed and increased cardiac, hepatosplanchnic, renal and gastrointestinal blood flows. 5. Respiratory volume had no effect on the cardiovascular effects of xylazine. However, respiratory volume modified the effects of phenylephrine on heart rate and changed the relative contributions of stroke volume and heart rate to the increased cardiac output. It also influenced the effects of phenylephrine on cardiac output distribution to the liver, epididimides and hepatosplanchnic bed and on blood flow through skeletal muscle and the large intestine. 6. Changes in respiratory volume of air ventilated pithed rats thus influence cardiac output, its distribution and regional blood flows. Such changes can also differently influence the responses of various vascular beds to phenylephrine whilst having no effect on their responses to xylazine. PMID- 2898958 TI - Excitatory amino acid antagonists and endogenous aspartate and glutamate release from rat hippocampal slices. AB - 1. The effect of excitatory amino acid agonists and antagonists on the efflux of endogenous aspartate and glutamate from the rat hippocampus in vitro was studied. 2. None of the compounds tested had any effect on the basal efflux of endogenous aspartate and glutamate. 3. 2-Amino-5-phosphonovaleric acid (APV), 2-amino-7 phosphonoheptanoic acid (APH) and MK-801 all reduced the potassium-evoked efflux of aspartate and glutamate by between 14.9% and 34.3% (P less than 0.05). 4. The depression of efflux brought about by APV was still observed in the presence of tetrodotoxin. 5. Neither N-methyl-D,L-aspartate nor quinolinic acid had any effect on the potassium-evoked efflux of aspartate and glutamate. 6. These results imply the existence of presynaptic amino acid receptors that are capable of modulating the efflux of endogenous aspartate and glutamate. PMID- 2898959 TI - Quinolinic acid effects on amino acid release from the rat cerebral cortex in vitro and in vivo. AB - 1. The effect of quinolinic acid, N-methyl-D,L-aspartate (NMDLA) and kainate on the release of endogenous and exogenous amino acids from the rat cerebral cortex in vitro and in vivo was studied. 2. Neither quinolinic acid nor NMDLA had any effect on the basal or potassium-evoked release of [3H]-D-aspartate from slices of rat cerebral cortex either in the presence or absence of magnesium. Kainic acid failed to modify the basal efflux of [3H]-D-aspartate but significantly inhibited (by 34.4% +/- 0.04%, P less than 0.05) the potassium-evoked release. 3. Neither quinolinate nor NMDLA had any effect on the basal efflux of endogenous amino acids from rat cortical slices either in the presence or absence of magnesium ions at concentrations between 10 microM and 5 mM. 4. Both NMDLA (1 mM) and quinolinate (5 mM) produced an efflux of endogenous aspartate (371.4% +/- 11.6%; 389.3% +/- 12.1%) and glutamate (405.4% +/- 13.6%; 430.1 +/- 8.7%) respectively from the rat cerebral cortex in vivo (P less than 0.01). The quinolinic acid-evoked efflux was abolished by the NMDLA antagonist, 2-amino-5 phosphonovaleric acid (200 microM). 5. Kainic acid also caused an efflux of endogenous amino acids from the rat cerebral cortex in vivo. However, the profile of this release was different from that produced by quinolinate and NMDLA. 6. The results add further support to the suggestion that quinolinic acid acts at the NMDLA-preferring receptor and may also explain the requirement for intact afferent projections for the neurotoxic effects of quinolinate to be manifested. PMID- 2898962 TI - Testicular torsion after orchidopexy. PMID- 2898960 TI - Effects of an intrathecally administered benzodiazepine receptor agonist, antagonist and inverse agonist on morphine-induced inhibition of a spinal nociceptive reflex. AB - 1. The effects of an intrathecally administered benzodiazepine receptor (BZR) agonist (midazolam, up to 50 micrograms), antagonist (flumazenil, Ro 15-1788, 5 micrograms) and inverse agonist (Ro 19-4603, 15 micrograms) on nociception and on morphine-induced antinociception were studied in rats. 2. By themselves, none of these compounds significantly altered pain threshold. 3. The BZR agonist midazolam enhanced the morphine-induced antinociceptive effect whereas the antagonist flumazenil did not alter it. In contrast, the BZR inverse agonist Ro 19-4603 decreased the morphine-induced antinociceptive effect. 4. Naloxone (1 mg kg-1 i.p.) completely reversed all these effects. 5. These results demonstrate that BZR agonists and inverse agonists are able to affect, by allosteric up- or down-modulation of gamma-aminobutyric acidA (GABAA)-receptors, the transmission of nociceptive information at the spinal cord level, when this transmission is depressed by mu-opioid receptor activation. PMID- 2898961 TI - The potential anxiolytic activity of GR38032F, a 5-HT3-receptor antagonist. AB - 1. The highly selective 5-HT3-receptor antagonist, GR38032F, has been tested in five animal models predictive for anxiolytic activity. 2. In the social interaction test in the rat and in a light/dark exploration test in the mouse, GR38032F dose-dependently released suppressed behaviour without modifying locomotor activity. 3. In the cynomolgus monkey and the marmoset, GR38032F reduced anxiety-related symptoms without causing sedation. In the marmoset, the effects were clearly dose-related. 4. GR38032F did not have any detectable activity in the water-lick conflict test in the rat. 5. We conclude that GR38032F is potentially a very potent anxiolytic agent without sedative, anticonvulsant or hypnotic activity. PMID- 2898964 TI - Effects of somatostatin antiserum on growth hormone levels in rats with periventricular lesions in the anterior hypothalamus. AB - To determine whether residual inhibitory control of growth hormone (GH) secretion in rats with lesions of the periventricular nucleus (PVN) and depleted median eminence content of somatostatin (SRIF) is due to SRIF, PVN-lesioned rats were treated with SRIF antiserum. Such treatment, in contrast to normal sheep serum, caused increased (P less than 0.0001) plasma GH in lesioned and control groups. These results indicate that biologically important amounts of SRIF are available in the PVN-lesioned rat. PMID- 2898963 TI - Activated charcoal, emesis, and gastric lavage in aspirin overdose. PMID- 2898965 TI - The origins and trajectories of somatostatin reticulospinal neurons: a potential neurotransmitter candidate of the dorsal reticulospinal pathway. AB - Somatostatin (SOMA)-immunoreactive neurons present in the nucleus gigantocellularis and nucleus raphe magnus formed the origins of a descending pathway from the rostral medulla to the spinal cord. This descending pathway was traced through the central medullary tegmentum and dorsolateral funiculus to innervate the dorsal horn. The location, trajectories and presumed inhibitory nature of SOMA in the spinal cord suggest that SOMA maybe a potential neurotransmitter candidate for the classic dorsal reticulospinal pathway. PMID- 2898966 TI - A simple two-step immunocytochemical method using protein A-peroxidase to stain immunoreactive cell antigens. AB - We report a simple two-step immunocytochemical method that uses staphylococcal protein A conjugated to horseradish peroxidase and the H2O2-3,3'-diaminobenzidine chromogenic reaction to stain neurons and fibers containing immunoreactive cell antigens. Our protein A-peroxidase method was found to produce stains of equal or superior quality to those of the classical 3-step peroxidase-anti-peroxidase (PAP) technique. Since the chromogenic reaction with protein A-peroxidase has low non-specific tissue binding, the reaction can be carried out at acidic pH with higher horseradish peroxidase activity and no significant increase in background. Using this method, we were able to produce clear stains of neurons and fibers containing tyrosine hydroxylase or fibers containing methionine-enkephalin. The use of protein A-peroxidase conjugate substantially simplified the immunocytochemistry procedure, and reduced both the time and cost of experiments. PMID- 2898968 TI - [Localization of proteases in the brain of rats after insulin coma]. PMID- 2898967 TI - Somatostatin(14) and -(28) but not somatostatin(1-12) hyperpolarize CA1 pyramidal neurons in vitro. AB - The three major prosomatostatin-derived peptides found within CNS neurons are a 28-amino acid peptide (SS28), a cyclic 14 amino acid peptide (SS14) and a 12 amino acid peptide (SS1-12). Immunohistochemical studies demonstrate a differential distribution of these related forms of somatostatin within CNS neurons and have led to the suggestion that SS1-12 may represent the predominant neurotransmitter form of this family of peptides. Intracellular recordings from CA1 pyramidal neurons in the in vitro rat hippocampal slice revealed that application of SS14 and SS28 in nanomolar concentration produced neuronal hyperpolarization; synaptic responses, recorded extracellularly, were also reduced. In contrast, we were unable to demonstrate a pre- or postsynaptic action of SS1-12 on these neurons. These results do not support the hypothesis that SS1 12 functions as a central neurotransmitter in area CA1 of the hippocampus. PMID- 2898969 TI - Surgical correction of burn scar contractures of the foot in children. AB - The results of reconstructive procedures for the treatment of burn scar contractures of the feet in 55 children undergoing 90 operations were reviewed. The patients were treated in all but one case by release of the contracture band with placement of a skin graft in the resulting defect. There was an overall recurrence rate of 15 per cent that was not affected by the use of split thickness versus full-thickness grafts. The time delay from the thermal injury to the reconstructive procedure was also found not to affect the outcome. Postoperative immobilization by the use of either a dynamic or an adynamic splint was found to be important both for preventing graft loss and for decreasing the rate of contracture recurrence. PMID- 2898971 TI - Infections and head injury: a potentially lethal combination. PMID- 2898970 TI - Simultaneous modeling of pharmacokinetics and pharmacodynamics: an improved algorithm. AB - An algorithm and computer program is presented that fits a largely non-parametric model to pharmacokinetic (PK) and pharmacodynamic (PD) data; it is an extension of a recently proposed approach. A PK model relates dose to plasma concentrations (Cp), a link model relates plasma concentrations to the concentration in the effect site (Ce), a PD model relates Ce to the effect. Both the PK and the PD model are non-parametric, but the link model is parametric. The extension presented here allows modeling of PK/PD data arising from non-steady-state experiments after arbitrary dosage. In addition, several data sets from the same individual (or from different individuals) can now be analyzed simultaneously, assuming the same link model for all, but allowing either all the PD models to be the same, or all to be different. PMID- 2898973 TI - Release of CMA statement on AIDS to highlight 1988 annual meeting. PMID- 2898972 TI - Alcohol, barbiturate and benzodiazepine withdrawal syndromes: clinical management. AB - The symptoms and clinical management of alcohol, barbiturate and benzodiazepine withdrawal syndromes are discussed in this article. People who suffer alcohol withdrawal should be admitted to hospital if they have medical or surgical complications or severe symptoms; supportive care and pharmacotherapy, especially diazepam loading, are the essential components of treatment. Barbiturate withdrawal requires pharmacotherapy and admission to hospital for patients who have taken more than 0.4 g/d of secobarbital or an equivalent amount of another barbiturate for 90 days or longer, or 0.6 g/d or an equivalent dose for 30 days or longer, or who have had withdrawal seizures or delirium; phenobarbital loading is recommended. Regular benzodiazepine therapy that has lasted at least 3 months should be gradually stopped. Short-acting agents should be replaced with long acting ones, such as diazepam, to avoid withdrawal symptoms. Most of these patients can be managed on an outpatient basis. PMID- 2898975 TI - Biochemistry of the human brain in old age and dementia. PMID- 2898974 TI - Production of bone-resorbing activity corresponding to interleukin-1 alpha by adult T-cell leukemia cells in humans. AB - The physicochemical properties and relationship of bone-resorbing activity and interleukin 1 (IL-1) produced by adult T-cell leukemia (ATL) cells and cell line were studied in vitro. The culture supernatant of ATL cell line, MT2, and peripheral blood lymphocytes freshly obtained from ATL patients had both IL-1 activity detected by the stimulation of murine thymocyte-proliferative responses and bone-resorbing activity detected by the stimulation of 45Ca release from prelabeled murine fetal bones. By Sephacryl S-200 column chromatography, both activities were eluted as a single peak at approximately Mr 15,000. By the chromatofocusing technique, the isoelectric point values of both activities were estimated as pH 4.8 and 5.2. Furthermore, both activities were absorbed with rabbit anti-IL-1 alpha antiserum, but not with anti-IL-1 beta antiserum. These results suggest that ATL cells and cell line produce bone-resorbing activity which corresponds to IL-1 alpha and that this IL-1 alpha is one of the most important causes of hypercalcemia in ATL patients. PMID- 2898976 TI - Drug consumption in patients with hip fractures compared with controls. AB - All drugs in a prospective series of 309 consecutive patients with cervical fractures and 300 with trochanteric fractures were recorded and compared with an age- and sex-matched randomly selected group from the city population files. A greater consumption of drugs was observed in the hip fracture group compared with the control group. Significant differences were observed for men regarding selective beta 2-adrenergic stimulants and xanthines, laxatives, phenothiazines and anti-psychotic drugs, as well as anti-glaucoma drugs. Women with hip fractures had a significantly greater consumption of diuretics, laxatives, insulin, phenothiazines and other antipsychotic drugs. PMID- 2898977 TI - Age-related prescribing patterns in general practice. AB - To examine differences in prescribing patterns in relation to patient age, all drugs dispensed during 1 week in a sample of community pharmacies were recorded. The mean number of drugs per prescription increased linearly from 1.5 in children aged 0-9 years to 2.8 in patients 80 years and over. The rate of prescribing of diuretics, benzodiazepines, non-steroidal antiinflammatory agents and drugs acting on the cardiovascular system increased markedly with advancing age. Drugs with a low therapeutic ratio were also prescribed more frequently for patients over 65 years. Psychotropic agents (15.9%), diuretics (13.8%) and cardiovascular drugs (13.7%) were the most commonly prescribed drugs in this age group. While a minority of elderly patients were prescribed a large number of drugs, prescribing rates overall did not appear excessive. PMID- 2898978 TI - Inheritance of allelic blueprints for methylation patterns. AB - We have developed a strategy to distinguish between the methylation patterns of homologous chromosomes in tissues, and to follow these patterns in human pedigrees. This genetic approach uncovered evidence of variation in the methylation of allelic sites on homologous chromosomes. This variation was tissue specific and reproducible after transmission through the germ line, demonstrating that homologous chromosomes have distinct blueprints for the tissue-specific regulation of methylation. Furthermore, this approach can be used to study the relationship between parental imprinting and methylation in native mammalian loci. PMID- 2898979 TI - Regulation of mucosal IgA production in vitro by autoreactive immunoregulatory T cells from murine Peyer's patches. AB - In this study, we investigated whether Peyer's patch-derived T-cell subsets participate in vitro in self major histocompatibility (MHC) class II antigen (Ag) mediated immunoregulatory circuits for gut-mucosal IgA isotype selection in the presence of Peyer's patch (PP)-derived syngeneic surface immunoglobulin M (sIgM) bearing B cells. When fresh (in vitro unstimulated) sIgM-bearing B cells were cocultured with fresh, PP-derived L3T4+ Vicia villosa-nonadherent (VV-) T cells (T helper (Th) cells), the production of all class-specific immunoglobulins (Ig), but, in particular, IgA, was enhanced two- to sixfold. This augmented Ig production was, however, reduced by nearly 50% when fresh PP-derived Lyt2+ VV-T cells (suppressor T cells) were added. Furthermore, addition of PP-derived L3T4+ VV+ and Lyt 2+ VV+ T cells abrogated, by nearly 100%, the suppression induced by the Lyt 2+ VV-T cells (contrasuppression). When lipopolysaccharide (LPS) stimulated, PP-derived sIgM-bearing B cells were cocultured with the Th cells, the production of each class-specific Ig was similarly enhanced, but Ig levels exceeded those obtained with cultures of the unstimulated B cells (P less than 0.001). Anti-I-A or anti-I-E monoclonal antibody (mAb) inhibited the induction of each immunoregulatory T-cell effector activity (P less than 0.001), and anti-I A/E inhibited it synergistically. Thus, unstimulated fresh PP-derived T cells appear to be activated and then to exert T-cell effector functions in the sequential development of helper, suppressor, and contrasuppressor immunoregulatory networks in the presence of PP-derived sIgM B cells and, particularly, LPS-preactivated sIgM B cells. Based on the blocking effect of anti I-A and/or anti-I-E mAb on the induction of each T-cell-mediated immunoregulatory function in class-specific Ig production, it appears that the autoreactive (self MHC class II Ag-reactive) activation of PP T cells evoked by Ia Ag on PP sIgM B cells largely controls mucosal IgA production by the latter cells. Furthermore, this immunoregulation by autoreactive effector T cells, especially the L3T4+ VV- helper T cell, may play a significant role in vivo in gut-mucosal IgA isotype production. PMID- 2898980 TI - Leg and foot injuries in racquet sports. AB - Injuries to the lower extremity are common in racquet sports. The acute injuries usually respond well to treatment. Chronic injuries may require more patience and sometimes a change of playing habits on the part of the player. Some chronic injuries will respond well to operative intervention but most will do well with conservative care. PMID- 2898981 TI - Urinary D-glucaric acid and serum hepatic enzyme levels in chronic alcoholics. AB - Urinary D-glucaric acid (DGA) and the activities of gamma-glutamyl transferase (GGT) and other hepatic enzymes in serum were determined in 33 noncirrhotic male alcoholics who had continued to consume alcohol until at least 24 h prior to the taking of samples. DGA excretion was significantly greater in them than in a group of 30 healthy controls (p less than 0.001), exceeding the upper reference level in 38% of the alcoholic cases (as compared with 88% for GGT). In the alcoholic patients, there was highly significant correlation between urinary DGA and serum GGT (r = 0.613, p less than 0.001), suggesting that in both cases the increased levels are due to enzyme induction. None of the biochemical variables studied were significantly correlated with estimated daily alcohol consumption. Urinary DGA levels fell off rapidly with abstinence, and in 31 alcoholic patients who had consumed no alcohol for 5 days, there was no statistically significant correlation between DGA excretion and serum GGT (r = 0.158, p congruent to 0.4). PMID- 2898983 TI - Pharmacological bases of the medical treatment of gastroesophageal reflux disease. PMID- 2898984 TI - Role of eicosanoids in diarrheal diseases. PMID- 2898982 TI - Alanine aminopeptidase in serum: biological variations and reference limits. AB - We studied the effect of various factors on the biological variation of alanine aminopeptidase (AAP, EC 3.4.11.2) in serum in a population of 2178 apparently healthy subjects and in subjects taking specific drugs. To measure AAP, we used an automated assay, with alanyl-4-nitroanilide as substrate. AAP activity concentrations were significantly higher in males than in females in all age groups between 10 and 55 years. The highest mean AAP values were found for children between 10 and 14 years. In male heavy smokers, AAP values were 8% higher than in moderate or nonsmokers (P less than 0.001); in females, this effect was less pronounced. AAP concentrations were higher in subjects consuming over 44 g of ethanol a day than in those consuming less (P less than 0.01 for men, P less than 0.05 for women). The use of oral contraceptives increased AAP values by 12% (P less than 0.001). Hypolipidemic drugs caused lower values for AAP in men (P less than 0.001). Subjects showing induction of gamma glutamyltransferase (EC 2.3.2.2) by anticonvulsant drugs had also higher AAP activities (by 23%). Taking these data into account, we established reference limits for AAP in serum. PMID- 2898985 TI - The role of alpha-adrenoceptor blockade in the antihypertensive effects of fenoldopam in humans. AB - Fenoldopam, a dopamine-1 receptor agonist, has been reported to exhibit alpha adrenoceptor-blocking actions in intact and isolated animal preparations. To determine whether alpha-adrenoceptor blockade contributes to its antihypertensive properties in humans, the effects of fenoldopam on the pressor responses to norepinephrine and angiotensin II were compared in eight normal volunteers. Fenoldopam (0.5 micrograms/kg/min) shifted the dose-response curves for both agonists to the right (p less than 0.05). Dose ratios for an increase in mean blood pressure of 10 mm Hg were 3.3 +/- 0.9 for norepinephrine and 3.2 +/- 0.6 for angiotensin II (p not significant). Consequently, fenoldopam is not a selective alpha-adrenoceptor antagonist at therapeutic concentrations in humans. PMID- 2898986 TI - Cumulative dose-response with infusion: a technique to determine neuromuscular blocking potency of atracurium and vecuronium. AB - The ability of cumulative dose-response techniques to obtain accurate data is most likely limited by redistribution and elimination of the drug during the study period. Therefore the usefulness of these techniques would be improved by replacing the amount of drug lost. This hypothesis was assessed for the intermediate-duration neuromuscular blockers vecuronium and atracurium, and calculations were made based on a pharmacokinetic model with an effect compartment. Sixty patients received either single doses (SD) (n = 36), cumulative doses (CD) (n = 12), or CD of vecuronium or atracurium with an infusion (CDI) to replace eliminated or redistributed drug (n = 12). The force of contraction of the adductor pollicis muscle in response to train-of-four stimulation was measured and recorded. Linear regressions were obtained between the logit transformation of neuromuscular blockade at the adductor pollicis and log dose. The potencies obtained with all three methods were within 20% of each other. For vecuronium the ED90 was (mean +/- SE) 0.034 +/- 0.002 (SD), 0.037 +/- 0.003 (CD), and 0.036 +/- 0.003 mg/kg (CDI). For atracurium the ED90 was 0.175 +/ 0.009 (SD), 0.206 +/- 0.019 (CD), and 0.179 +/- 0.015 mg/kg (CDI). Calculated values corresponded well with measured values. The calculations predicted that the agreement between single- and cumulative-dose techniques would be improved if (1) the dose increment was increased, (2) the elimination half-life was increased above 20 minutes, or (3) an infusion was added.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2898987 TI - Lymphoid tissue responses to perfluorocarbon emulsion in rats: time course effects relative to immune challenge. AB - 1. The effects of either intraperitoneal (i.p.) or intravenous (i.v.) injection of low doses (10 ml/kg) of the commercial emulsion, Fluosol-DA 20% (F-DA), on lymphoid tissues and antibody production against sheep red blood cells (SRBC) have been studied relative to the timing of immunization in rats. 2. Spleen and liver weights were significantly increased in response to injection of F-DA although no consistent pattern was observed. 3. Thymus weight was decreased following F-DA injection in some experimental groups whereas mesenteric lymph node (MLN) weights were unchanged throughout. 4. The mean plasma antibody titre to SRBC was significantly increased in some groups of animals injected with F-DA both before or after immunization; maximum titres were observed following injection of emulsion simultaneously with SRBC. 5. These results show that lymphoid tissue weights and plasma antibody titres in rats immunized with SRBC vary according to the timing and route of a previous or subsequent injection of F DA. PMID- 2898989 TI - The cardiac effects of arginine vasotocin in amphibians. AB - 1. The cardiac effects of arginine vasotocin (AVT) on isolated atria were examined in three anuran and one urodele species. 2. AVT produced dose-related positive chronotropic and inotropic responses. 3. The responsiveness of the atrial tissue varied among species. 4. Both the basal atrial rate (AR) and tension (T) were attenuated in the presence of phentolamine and propranolol, alpha- and beta-adrenergic antagonists. Isoproterenol, a beta-adrenergic agonist, increased both AR and T, an effect which would be inhibited by propranolol. 5. The effects of AVT on both AR and T were not inhibited by alpha- and beta adrenergic blockers, nor by verapamil and imidazole with the dosages used in the present study. 6. On the contrary, the effects of AVT on AR, but not T, was enhanced in the presence of both alpha- and beta-adrenergic blockers. 7. The mechanism of action of AVT on the amphibian atrium remains unknown. PMID- 2898988 TI - Actions of dopamine and related amines on reserpinized and chronically denervated vasa deferentia of the rat. AB - 1. Reserpine, chronic guanethidine denervation and alpha-adrenoceptor antagonists were used to distinguish between presynaptic and postsynaptic actions of exogenous dopamine (DA), octopamine (OA), tyramine (TA) and noradrenaline (NA) on the rat vas deferens. 2. TA has only a presynaptic action while DA and OA have mixed presynaptic actions (releasing endogenous NA) and postsynaptic actions. 3. The postsynaptic actions of DA and OA are likely to be mediated by alpha adrenoceptors rather than by specific receptors. PMID- 2898990 TI - Hepatic drug metabolizing enzyme activity in the channel catfish, Ictalurus punctatus. AB - 1. Several pathways of drug metabolizing enzymic activity were measured in hepatic fractions of the channel catfish and rat using model substrates. The pathways examined included the O-demethylation of p-nitroanisole, microsomal ester hydrolysis of procaine and glucuronidation of p-nitrophenol, and the cytosolic acetylation of sulfamethazine and sulfation of 2-naphthol. Catfish liver preparations were incubated at both 25 degrees C and 37 degrees C. 2. The oxidative metabolism of p-nitrophenol was only one-eighth that of the rat at 37 degrees C and one-twelfth that of the rat at 25 degrees C. 3. Procaine ester hydrolysis was negligible in catfish microsomal preparations. 4. At 37 degrees C, p-nitrophenol glucuronidation was equivalent in catfish and rat microsomes. 5. Catfish cytosolic preparations exhibited N-acetyltransferase and arylsulfotransferase nearly comparable to those of the rat. 6. Rates of glucuronidation and sulfation were higher at 37 degrees C than at 25 degrees C in hepatic fractions of catfish. PMID- 2898991 TI - B-naphthoflavone induction and its effect on hepatic phospholipid metabolism in rainbow trout (Salmo gairdneri). AB - 1. B-naphthoflavone (BNF) induction of microsomal cytochrome P-488 and its effect on liver phospholipid metabolism were examined in rainbow trout (Salmo gairdneri) 24 and 96 hr after intraperitoneal injection. 2. Cytochrome P-448 content increased at 96 hr to approximately double the cytochrome content of control fish. 3. Computer-analyzed laser densitometry scans of LDS-polyacrylamide gels of 96 hr BNF-treated liver microsomes showed a 90% increase in cytochrome P-448 levels. 4. A 34% increase in microsomal phospholipid (mumol/mg protein) was observed 24 hr after BNF injection, with a marked increase in choline, ethanolamine and inositol phospholipids. 5. Following 96 hr of exposure to BNF some differences in enzyme activity were noted; choline kinase and cytidylyltransferase activities were reduced, while a marked increase was observed in choline phosphotransferase activity. In light of current information on induction of liver microsomal phospholipid metabolism in mammals, the results of the this study suggest that trout do not respond like mammals to inducers of monooxygenase activity. PMID- 2898993 TI - Recovery of acetylcholinesterase activity after irreversible inhibition by organophosphorous compounds in embryonic development. AB - 1. Recovery of acetylcholinesterase (AChE) activity was studied using the embryos of sea urchins Strongylocentrotus intermedius and S. nudus, embryos of axolotl Ambystoma mexicanum and in the chick embryo muscle culture treated by "irreversible" organophosphorous inhibitors (OPI). 2. AChE activity was assayed by a modified Ellman's procedure. 3. It follows from the data obtained that, unlike the plutei of sea urchins and the monolayer culture of chick embryo muscle cells, the embryos of axolotl show a compensatory increase in AChE biosynthesis after inhibition by OPI. 4. This mechanism is assumed to be related to the presence of a well developed neuromuscular system in the A. mexicanum embryos. 5. It is possible that acetylcholine accumulated as a result of partial AChE inhibition is responsible for the compensatory increase in AChE biosynthesis. PMID- 2898992 TI - Deltamethrin induced changes in choline transport and phosphorylation activities in synaptosomes from the optic lobe of squid, Loligo pealei. AB - 1. Deltamethrin, a powerful synthetic pyrethroid causes a significant change in choline transport in freshly prepared synaptosomes from squid optic lobes. 2. At resting state (nondepolarized) such an effect manifested as a reduction of 14C choline uptake in a short term (1 min) uptake experiment. 3. At depolarized state, or under conditions where synaptosomes are subjected to osmotic, aging and other stress conditions, deltamethrin caused stimulation of 14C-choline uptake, resulting in elevation of the levels of total radiocarbons in synaptosomes. 4. Such changes are accompanied with changes in overall phosphorylation activities in synaptosomes. PMID- 2898994 TI - Effect of 2-mercaptoethanol on the electrophoretic behavior of rat and dogfish metallothionein and chromatographic evidence of a naturally occurring metallothionein polymerization. AB - 1. Metallothionein behavior in SDS-PAGE has been characterized. 2. It has been found that metallothionein behavior in this electrophoretic system depends upon the reducing environment. Migration as a well-defined protein band is only achieved in the presence of 2-100 mM 2-mercaptoethanol. 3. Within those 2 mercaptoethanol levels, both rat and dogfish metallothionein migrate as a protein with a molecular weight several times higher than that expected by amino acid analyses. This is not due to molecule oxidations, since this effect is promoted by the presence of 2-mercaptoethanol. 4. No effect of 2-mercaptoethanol on metallothionein behavior is found in conventional PAGE. 5. The present results suggest that to study the effect of 2-mercaptoethanol in SDS-PAGE is a simple and accurate way to identify a protein as metallothionein. 6. It has also been found that metallothionein aggregates naturally in the absence of ionic strength. PMID- 2898995 TI - Noradrenaline, dopamine, 5-hydroxytryptamine and tryptophan concentrations in the brains of four cohabiting species of fish. AB - 1. The concentrations of the neurotransmitters noradrenaline, dopamine and 5 hydroxy-tryptamine and the amino acid tryptophan were determined in the telencephalon, optic lobes and rest of the brains of four species of fish collected from a stream in central Saskatchewan. 2. The species investigated were white sucker (Catostomus commersoni), longnose sucker (Catostomus catostomus), longnosed dace (Rhinichthys cataractae) and northern pike (Esox lucius). 3. Significant differences were found in the concentrations of amines in different regions of the brain within species and within the same brain region between species. 4. These results may be related to the phylogenetic differences or to patterns in brain development evolved by fish species to adapt to particular lifestyles. PMID- 2898996 TI - Peroxidation of mullet and rat liver lipids in vitro: effects of pyridine nucleotides, iron, incubation buffer, and xenobiotics. AB - 1. Lipid peroxidation was observed in homogenates of mullet and rat livers and was affected by the specific conditions used for the in vitro assays. 2. Lipid peroxidation was altered by the buffer used in the assays and was dependent on the amount of Fe added to the assay. 3. Lipid peroxidation was stimulated by both NADH and NADPH and by the xenobiotics, CCL4 and DEM. 4. Lipid peroxidation was observed in microsomes of mullet livers and was inhibited by addition of cytosol. PMID- 2898997 TI - A comparison of toxins isolated from the cyanobacteria Oscillatoria agardhii and Microcystis aeruginosa. AB - 1. A toxin isolated from a strain of Oscillatoria agardhii var. was compared to a peptide toxin isolated from Microcystis aeruginosa. 2. The Oscillatoria toxin possessed similar hepatotoxic properties on mice as the Microcystis toxin but had a higher LD50 than the latter; 320 micrograms/kg compared to 43 micrograms/kg (i.p. mouse), respectively. 3. Ultra-violet and infra-red spectra showed that the Oscillatoria toxin is a peptide which is not identical to the Microcystis toxin. 4. The spectra also indicated some structural similarities in these toxins. PMID- 2898998 TI - Influence of lead exposure on catecholamine metabolism in discrete rat brain nuclei. AB - 1. Using the rat exposed both acutely and chronically to lead as a model of lead neurotoxicity, various parameters of catecholamine metabolism were investigated. 2. The steady-state concentrations of noradrenaline, adrenaline and dopamine together with the activities of tyrosine hydroxylase and phenylethanolamine N methyl transferase were measured in discrete brain nuclei--periventricular, paraventricular, median eminence, posterior and anterior hypothalamus, caudate putamen and globus pallidus. 3. Lead exposure resulted in significant fall in the activity of the rate-limiting enzyme of catecholamine synthesis, tyrosine hydroxylase which was associated with alterations in concentrations of catecholamines in the median eminence, periventricular nucleus and anterior hypothalamus. 4. No other brain nuclei investigated exhibited any effect of lead on the catecholaminergic nervous system and, therefore, the effect of lead on rat brain can be considered to be regionally specific. PMID- 2898999 TI - Effects of lead exposure on rat brain catecholaminergic neurochemistry. AB - 1. The effects of lead on catecholaminergic neurotransmission have been investigated. 2. Using the rat as a model, animals were exposed both acutely and chronically to lead. The levels of catecholamines, noradrenaline, adrenaline, and dopamine along with the activities of tyrosine hydroxylase and phenylethanolamine N-methyl transferase were measured in 5 brain regions--cerebral cortex, brainstem, hippocampus, anterior and posterior hypothalamus. 3. A lead related reduction in the activity of tyrosine hydroxylase was observed in association with alterations in steady-state levels of the catecholamines in the posterior and anterior hypothalamus. 4. Thus, lead exposure, known to result in behavioural changes, is associated with localised neurochemical effects on the hypothalamus. PMID- 2899000 TI - Sampling and storage conditions of rainbow trout liver affects monooxygenase and conjugation enzymes. AB - 1. The effect of storage conditions of rainbow trout (Salmo gairdneri) liver on monooxygenase and conjugation enzyme activities was studied. Fish livers or whole fish were frozen and stored for various periods of time at -4, -20 or -80 degrees C. 2. Freezing the whole fish at -20 degrees C affected the biotransformation enzyme activities dramatically. The loss of monooxygenase activity exceeded up to one-tenth of the initial rate in 17 days. UDP-Glucuronosyltransferase activity increased 50%. Glutathione S-transferase appeared to be the most durable enzyme. 3. When the whole fish were stored in an ice-bath at -4 degrees C for up to 24 hr the activities measured decreased only half of that when frozen for 3 days. 4. When it is impossible to freeze the tissues studied in liquid nitrogen the activities are best preserved when whole, decapitated, bled fish are kept in an ice-bath for less than 24 hr. PMID- 2899001 TI - A comparative study of some oxidative and conjugative drug metabolizing enzymes in liver, lung and kidney of sheep. AB - 1. The comparative distribution of cytochrome P-450 monooxygenase system, glucuronyltransferase, glutathione S-transferase and N-acetyltransferase was studied in the liver, lung and kidney of young male sheep. 2. The sheep liver was characterized by a lack in glutathione S-transferase activity with isoniazid as substrate. 3. The oxidative drug metabolizing enzymes of lung were generally close to those of liver; benzphetamine N-demethylase and ethoxycoumarin O deethylase were even found to be higher in lung (213 and 148%, respectively). 4. Pulmonary conjugative and both renal oxidative and conjugative systems accounted only for 9-38% of hepatic corresponding enzymes. 5. The enzyme determination in various sampling sites of the three organs, demonstrated the homogeneous distribution of all investigated monooxygenases and transferases in liver, lung and kidney of sheep. PMID- 2899002 TI - Evolution of neurotransmitter-related markers in the vertebrate telencephalon. Comparative microchemical study in discrete brain regions of a frog and a turtle. AB - 1. Neurochemical markers related to cholinergic, GABAergic and glutamatergic/aspartatergic neurotransmission have been measured in telencephalic areas obtained by microdissection from frog (Rana esculenta) and turtle (Pseudemys scripta elegans) brain. 2. In both species, pallial areas showed remarkably higher levels of synaptosomal D-3H-aspartate high affinity uptake than basal regions. Conversely, striatal and septal areas possessed higher levels of the GABAergic marker glutamate decarboxylase (GAD) than the pallium. 3. A differential distribution of GAD was noticed in striatal regions, highest levels of the enzyme being present in the ventral striatum, followed by the nucleus accumbens and the dorsal striatum. 4. Cholinergic markers choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were rather uniformly distributed in the frog telencephalon, while, in the turtle, cholinergic markers were several-fold higher in the basal telencephalon, particularly in the striatum, than in the pallium. 5. The turtle dorsal ventricular ridge possessed ChAT levels more similar to the striatal than to the cortical ones. On the contrary, D-3H-aspartate uptake in the dorsal ventricular ridge was close to the highest levels found in cortical areas. 6. The quantitative neurochemical approach adopted for the present study appears to be a useful tool to investigate the problem of homologies and to gain new information on the evolution of neuron populations and neuronal connections in the vertebrate telencephalon. PMID- 2899003 TI - Occurrence and effects on motility of bombesin related peptides in the gastrointestinal tract of the Atlantic cod, Gadus morhua. AB - 1. Low levels of bombesin-like immunoreactivity (less than 1.10 pmol/g tissue), eluting at the same position as synthetic bombesin and litorin, have been measured in muscle and mucosa of the gastrointestinal canal of the cod, Gadus morhua. 2. Immunohistochemistry showed bombesin-like material in endocrine cells and nerves throughout the gut. Intensity and absorption controls indicated a difference in character between the peptides present in stomach and intestinal muscle respectively. 3. Stomach motility was stimulated by bombesin (pD2 = 8.27 +/- 0.19), litorin (8.03 +/- 0.04) and (less potently) GRP (less than 7.46 +/- 0.22). Litorin (8.21 +/- 0.31) had an inhibitory effect on intestinal motility. 4. In conclusion, one or several bombesin-like peptides may be involved in the control of gastrointestinal motility in the cod, causing opposite effects on stomach and intestine. The structure of the peptide in gastric nerves may differ from that in intestinal nerves. PMID- 2899004 TI - Monoamine oxidase and semicarbazide sensitive amine oxidase activities in toad liver mitochondria. AB - 1. The deamination of 5-HT and PEA has been assayed by a radiochemical method in mitochondria isolated from toad liver. 2. Time courses of 5-HT and PEA deamination indicate that when PEA is used as the substrate, higher specific activities are obtained. 3. 5-HT is deaminated by MAO A and partially by a SSAO like enzyme. 4. PEA is deaminated exclusively by SSAO and, MAO B activity, at least under the adopted experimental conditions, is not detectable. PMID- 2899005 TI - Histamine-induced potentiation of cholinergic transmission in chick oesophagus (Gallus gallus). AB - 1. The effects of histamine on cholinergic nerve transmission were investigated in the oesophagus of the chick (0-29 days old). 2. Histamine potentiated the contractile responses produced by vagal or transmural nerve stimulation and by the ganglionic stimulant (DMPP) with the increase of tonus of oesophagus. On the other hand, a selective H2 agonist, 4-methylhistamine, did not have any effect. 3. The sensitivity of oesophagus to ACh did not change in the presence of histamine (0.2-2 microM). 4. Mepyramine but not metiamide antagonized the contractile and potentiating effects of histamine. 5. From these findings, it is concluded that histamine preferentially acts on H1-receptors located in cholinergic neurones to facilitate cholinergic transmission in the chick oesophagus, potentiating the nerve-mediated contraction. PMID- 2899007 TI - The effect of feeding tall fescue seed infected by Acremonium coenophialum on pregnancy and parturition in female rats. AB - 1. Female Sprague-Dawley rats (Rattus norvegicus) were randomly assigned to various dietary treatments containing: (1) 100% Purina rodent chow, ad libitum; (2) same as 1, but restricted to daily intake of 7; (3) 50% rodent chow (w/w) and 50% endophyte-free tall fescue (Festuca arundinacea) seed; (4) same as 3, but restricted to intake of 5; (5) 50% rodent chow, 25% endophyte-free tall fescue seed and 25% endophyte-infected (Acremonium coenophialum) tall fescue seed; (6) 50% rodent chow, 12.5% endophyte-free and 37.5% endophyte-infected tall fescue seed; and (7) 50% rodent chow and 50% endophyte infected tall fescue seed. 2. Average daily feed intakes and average daily weight gains decreased with higher levels of endophyte infected seed. 3. Frequency of litter production was affected by all endophyte-infected containing diets. 4. Conception was reduced only in dietary treatment (7). 5. Litter weights, number of pups per litter and weight per pup were proportionally reduced as higher levels of infected seed were incorporated in the ingested diets. PMID- 2899006 TI - Effects of a testicotoxic dose of cadmium on the liver and drug metabolism in the rat. AB - 1. The effect of an acute testicotoxic dose of cadmium (CdCl2.H2O, 2.0 mg/kg i.p.) on liver morphology and drug-metabolizing enzyme activities were studied in adult male and female rats. 2. Cd treatment to female rats caused a slight and reversible decrease in hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and aminopyrine N-demethylase (APND) activities. 3. No significant changes were noted in the liver morphology, serum alanine aminotransferase activities, enzyme induction by phenobarbital and 3-methylcholanthrene, and glucuronosyl-transferase (GT) and glutathione S-transferase (GST) activities. 4. The same Cd treatment to male rats, however, resulted in a much more pronounced and prolonged reduction in AHH and APND activities, which was attributable to a Cd-induced testicular necrosis and, hence, impairment of androgen secretion. 5. Accordingly, Cd treatment to castrated male rats did not lower the enzyme activities any further, and full recovery of activities was obtained after the administration of testosterone. 6. Both GT and GST, the two sex-independent enzymes, were not significantly affected by either Cd or gonadectomy in the male rat. 7. The present data show that a low acute dose of Cd induces chemical castration without severely altering hepatic function. PMID- 2899008 TI - Myocardial responsiveness to isoproterenol and calcium: a comparison of SD and F344 rats. AB - 1. Inotropic effects of isoproterenol and extracellular Ca2+ were compared in left atrial muscle isolated from F344 and SD rats. Preparations from the F344 strain were more sensitive to the actions of both agents. 2. The chronotropic action of isoproterenol was not different in right atria isolated from the two strains. 3. This suggests that the strain-related difference in responsiveness to the inotropic effect of isoproterenol is not caused by heterogeneity in the beta adrenoceptor/adenylate cyclase system but rather by variations in excitation contraction coupling. PMID- 2899009 TI - Enzymatic histamine catabolism in vertebrate ontogenesis. A comparative study. AB - 1. The synthesizing and degrading activities of histamine were determined in the liver and small intestine of developing guinea pig and chick embryos. 2. Though increasing with age, HDC values were always 2-3 orders of magnitude lower than those of degrading enzymes. 3. DAO activity on the other hand was 10-100 fold higher than HMT at all ages studied, suggesting a decisive role for oxidative deamination in control of tissue histamine levels. 4. Generally histamine levels were higher in tissues of developing guinea pig than chick embryo, however, in the laying hen intestine histamine concentration was approximately 5 times greater than in the adult guinea pig intestine. PMID- 2899010 TI - The effects of DDE, PCB and chlordane on the binding of progesterone to its cytoplasmic receptor in the eggshell gland mucosa of birds and the endometrium of mammalian uterus. AB - 1. The specific binding of progesterone to its cytoplasmic receptor in the mucosa of the shell gland from egg-laying ducks, domestic fowls and from the endometrium of the rabbit uterus was compared. The effect of DDE, PCBs and chlordane added in vitro was also studied. 2. The KD value for progesterone with regard to its receptor was about four times lower in the domestic fowl and the rabbit than in the duck. 3. The chlorinated hydrocarbons decreased the binding of progesterone to its receptor. Their potency was higher in the duck than in the domestic fowl. In rabbit uterine mucosa their effects were similar to those observed in the duck. 4. DDE is an inhibitor of calmodulin: other calmodulin inhibitors as calmidazolium and trifluoperazin also reduced the binding of progesterone in similar concentrations. It is suggested that DDE reduced the progesterone binding by inhibiting calmodulin. PMID- 2899011 TI - Hypomagnesaemia, hypoalbuminaemia and plasma lipid changes in rats following the oral administration of ciclosporin. AB - 1. The effects of orally administered ciclosporin (40, 50 or 80 mg/kg body wt) on plasma magnesium, albumin, total cholesterol and triglycerides have been studied in male Wistar rats. 2. Plasma magnesium and albumin were significantly lower in rats dosed with ciclosporin (40, 50 or 80 mg/kg) after 14 days. 3. Variable changes of plasma cholesterol and triglycerides were observed. Some implications of the inter-relationships of magnesium, albumin and plasma lipids in ciclosporin treatment are discussed. PMID- 2899014 TI - Effect of ionic contents in saline on depolarizing afterpotential induced by phenothrin and methoxychlor. AB - 1. The depolarizing afterpotential induced by phenothrin and methoxychlor in crayfish giant axons was measured intracellularly. 2. Changes in the K+ ion concentration did not affect the depolarizing afterpotential when evaluated as the membrane potential. 3. Addition of tetrodotoxin or replacement of the Cl- ions by OAc- ions or of the Na+ ions by choline ions reduced the depolarizing afterpotential and the action potential. 4. A ratio of the reduction of the depolarizing afterpotential in saline that contained OAc- ions to that of the action potential was similar to that measured in the saline containing tetrodotoxin. 5. With the increase in the choline concentration, the relative value of the depolarizing afterpotential to that measured before the replacement decreased almost linearly with that of the decrease in the action potential. PMID- 2899012 TI - The actions of phenol and pentachlorophenol (PCP) on axonal conduction, ganglionic synaptic transmission, and the effect of pH changes. AB - 1. A comparison of phenol, pentachlorophenol (PCP) and procaine effects on axonal conduction were studied in vitro in the sciatic nerves of toad. PCP and procaine were respectively 6.3 and 3.15 times more potent than phenol in blocking axonal conduction. 2. Effects of PCP on synaptic transmission were studied in vitro in the eighth sympathetic ganglion of toad. 3. Axonal conduction block and synaptic transmission block by phenol was reversible, but not that by PCP. 4. When the PCP ionization was increased, a lesser per cent reached the site of action, reducing its capacity to block the axonal conduction and ganglionic transmission. 5. PCP plus, 3,4-Diaminopyridine (3,4-DAP) decreased synaptic transmission block from post-ganglionic compound action potential (CAP) responses to supramaximal preganglionic stimulation. PMID- 2899013 TI - Pharmacologically induced changes in the latency of digastric reflexes in 1-7 day old rabbits. AB - 1. The naturally occurring change in latency of the digastric reflex from long (40-70 msec) to short (15-35 msec) in the first week of life was studied in rabbits using drugs known to affect GABAergic and glycinergic transmission. 2. Usually the long or the short latency reflex response appeared alone but after strychnine both appeared together. 3. The long latency responses were favoured by the GABA blockers bicuculline and picrotoxin; periodically rhythmic activity was also elicited. 4. The short latency responses were favoured by the GABA agonists pentobarbitone and diazepam. PMID- 2899015 TI - Chromosome aberrations in cultured central mudminnow heart cells and Chinese hamster ovary cells exposed to polycyclic aromatic hydrocarbons and sediment extracts. AB - 1. Genotoxicity experiments were conducted with cultured fish cells to determine if the high frequency of epidermal papillomas observed in lemon sole from Sturgeon Bank, where a sewage treatment plant discharges, could be correlated with contamination of the sediments with chemicals such as 3,4-benzopyrene. 2. The frequency of chromosome aberrations was measured in cultured Umbra limi heart (U1-H) and Chinese hamster ovary (CHO) cells following exposure to the polycyclic aromatic hydrocarbons (PAH) 3,4-benzopyrene (BP), 1,2,5,6-dibenzanthracene (DBA), 1,2-benzanthracene (BA), and pyrene (PY), activated using S9 prepared from rainbow trout liver. 3. An increase in the chromosome aberration frequency was only observed following exposure to fish S9-activated BP in both cell lines. 4. Following exposure of the cells to both Sturgeon Bank and Spanish Bank sediment extracts, it was determined that a higher level of toxic and genotoxic activity was associated with the Sturgeon Bank sediments. 5. Since the detection of PAH genotoxicity requires the presence of S9, and since a higher level of genotoxic activity was noted following sediment extract exposures with no S9 present, this suggests that the extracts contain a complex mix of chemicals, some of which express genotoxic activity. 6. An assessment using the micronucleus test failed to indicate in vivo genotoxicity in fish collected from Sturgeon and Spanish Banks. 7. It was, therefore, difficult to associate the observed sediment genotoxicity with the previously noted high incidence of epidermal papillomas in lemon sole from this area. PMID- 2899016 TI - Identification of tissues and cells producing erythropoietin in the anemic mouse. PMID- 2899017 TI - Beta-blocker action on lymphocyte proliferative response in essential hypertension. AB - The proliferative response of phytohaemagglutinin (PHA) - stimulated lymphocytes of healthy donors and hypertensive subjects was analysed according to 3H thymidine incorporation and cell cycle phase position on a flow cytofluorimeter. 3H-thymidine uptake and the percentage of cells in (S + G2) phase were significantly lower in hypertensive patients. After short-term propranolol administration the lymphocyte blastogenic response in essential hypertension increased by 30--100%. The data suggest that the change in mitogenic response of lymphocytes in essential hypertension results from changes in the distribution of lymphocyte subclasses. The connection between the sympathoadrenal and immune system is discussed. PMID- 2899018 TI - Undissolved sulfasalazine tablets. PMID- 2899019 TI - Effect of SMS 201-995 in rapidly progressive diabetic retinopathy. PMID- 2899020 TI - Glutamergic transmission and cardiovascular apparatus in normotensive rats. AB - The cardiovascular effects induced by L-glutamic acid (G) on the cardiovascular apparatus of normotensive ethyl urethane-anaesthetized rats have been evaluated. (a) When administered i.v. (1 to 100 mg/kg) G induced a transitory and dose dependent increase of arterial pressure (AP) with very moderate sinus bradycardia. It was antagonized by L-glutamic acid diethyl ester (GDEE, 0.1 to 100 mg/kg i.v.). (b) The intracerebroventricular (i.c.v.) administration of G (third ventricle, right lateral ventricle, posterior hypothalamus and striatum) at a dose of 0.1 to 10 mg/an induced a transitory and dose-dependent increase of AP, abolished by i.c.v. GDEE (1 to 10 mcg/an). (c) G hypertension was reduced by several procedures, i.e. catecholamine depletion, alpha 1, alpha 1 and alpha 2 or beta adrenergic blocks, alpha 2 central adrenergic stimulation, Ca2+ transmembrane or gangliary block, surrenectomy, and spinal transection at C7. (d) Atropine, bilateral vagotomy and sinus carotidal denervation increased G hypertension. (e) Therefore the bradycardia does seem to be due to a reflex mediated effect via sinus carotid and aortic baroreceptors. (f) These data show that glutamergic transmission also participates through a central mechanism in the regulation of cardiovascular function in rats, via an increase in central sympathetic efferent activity. PMID- 2899021 TI - Neuroleptic plasma concentrations and clinical response: in search of a therapeutic window. AB - There is much interest in finding a therapeutic window for commonly used neuroleptics so that dosage can be individualized and side effects minimized. The authors review specific requirements of good study design and survey the literature that has investigated the relationship between therapeutic response and plasma concentrations of neuroleptics. The evidence from a number of fixed dose haloperidol studies suggests, but does not yet prove, the existence of a therapeutic window for this compound. PMID- 2899022 TI - [Antibodies to the human T-cell leukemia virus in the blood serum of the inhabitants of Sakhalin and Iuzhno-Kuril'sk]. AB - Two immunological tests were used in testing of 808 blood serum samples from inhabitants of Sakhalin and of the city of Yuzhno-Kurilsk for antibodies against HTLV-1 etiologically associated with human T-cell leukemia. Antibodies to HTLV-1 were detected in 4.2% of Nivkhs, 1.2% of Oroks and 1.5% of Russians. The highest level of virus-carriers reaching 6.0% was detected in Nivkhs from the middle part of Sakhalin. The antibodies were detected more often in persons of old age and in women. PMID- 2899023 TI - [Antimetastatic effect of the delta-sleep peptide during stress in mice with Lewis' lung carcinoma]. AB - The experiments on C57Bl mice with metastatic Lewis lung carcinoma have shown that peptide delta-sleep (DSIP) lowers the stimulation of metastatic spreading which is observed in combination of the surgical removal of the tumour with the emotional-painful stress. The antimetastatic effect is accompanied by stabilization of neurohumoral indices, by a decrease in the intensity of lipid peroxidation and of the acid cathepsin activity in the blood vessels and in the lung tissue. PMID- 2899024 TI - [Immunity, neuropeptides and psychiatry]. AB - The author proposes and defends new lines in psychiatric research, aimed not primarily at the study of etiology but of pathogeny. Two systems recognize self from non self: the nervous and the immune systems. These communicate with each other by means of hormones, growth factors, neurotransmitters and neuromodulators. The biochemical family of the neuropeptides therefore plays an important role in the transmission of this information and participates in the complex regulatory mechanisms which insure the physical and psychical equilibrium of the individual. Disorders of such regulation lead to or participate in the psychosomatic diseases and to psychiatric pathology. The author proposes that, in order to elucidate the normal complex regulatory mechanisms, one should first carry out studies on neuropeptides in primitive living organisms and observe the functional capacities of lymphocytes and thymocytes from psychiatric patients. PMID- 2899025 TI - Transglutaminase activity along the rat small bowel and cellular location. AB - A recent report indicates a relationship between human transglutaminase (TG) jejunal mucosa activity and celiac disease. We investigated the enzyme distribution along six consecutive small bowel segments of mucosa and tested TG activity on brush border membranes obtained from whole mucosa homogenate in Wistar rats. TG activity was significantly present in jejunal mucosa even if mostly detected in the distal part of small intestine. Our study indicates highest enzymatic activity in the subcellular fraction containing organelles and cellular membranes (66.8%) while a 7% activity was associated with the brush border fraction. PMID- 2899026 TI - Role of the N-terminus of rat pheochromocytoma tyrosine hydroxylase in the regulation of the enzyme's activity. AB - Activation of rat pheochromocytoma tyrosine hydroxylase by limited tryptic proteolysis was investigated. The modifications produced upon the enzyme's structure were analyzed with the use of sodium dodecyl sulfate/polyacrylamide gel electrophoresis and tyrosine hydroxylase activity was measured all through the digestion. During the proteolysis the activity of tyrosine hydroxylase was elevated threefold at the same time as a 56-kDa tryptic fragment was formed. When the enzyme was phosphorylated, at its N-terminal region, by a kinase copurified with tyrosine hydroxylase, the major 56-kDa species did not appear to be phosphorylated on the autoradiograph, suggesting that it was derived from the native subunit by cleavage of the N-terminal of the protein. The reactivity of the 2/40/15 anti-(tyrosine hydroxylase) monoclonal antibody with the N-terminal of tyrosine hydroxylase was also investigated, using the Western-blot technique. This antibody reacted with the 62-kDa hydroxylase subunit but not with the 60-kDa tryptic fragment; the amino acid sequences of these two species showed that the 60-kDa fragment lacked the first 16 N-terminal amino acids of the native molecule. These results suggest that the N-terminal region of tyrosine hydroxylase is apparently responsible for an inhibition of the hydroxylase activity and that the first N-terminal amino acids of the hydroxylase are necessary for the recognition of the enzyme by its antibody. PMID- 2899027 TI - Antibody response to pertussis toxin in patients with clinical pertussis measured by enzyme-linked immunosorbent assay. AB - Serum antibody response to pertussis toxin was measured by enzyme-linked immunosorbent assay in 172 patients with clinical symptoms typical of whooping cough. The diagnosis was verified by culture in 100 patients. Serum antibodies were either not detectable or present only at low levels in sera obtained in the early stage of disease. Significant changes in serum levels of IgG, IgM and/or IgA were demonstrated in 143 patients (83%). The lack of comparable increases in most of the other patients may be due to inappropriate timing of serum collection. Thus, detection of antibodies against pertussis toxin in paired serum samples can be used for serological diagnosis of pertussis. However, the presence of IgM and/or IgA in a single serum sample does not confirm a diagnosis of pertussis, since such antibodies were found in healthy adults as well as in patients two years after the disease. High levels of these antibodies are, however, suggestive of on-going or recent disease. PMID- 2899028 TI - Growth hormone releasing factor and somatostatin concentrations in the milk of lactating women. AB - The concentrations of growth hormone releasing factor (GRF) and somatostatin, two hypothalamic neuropeptides involved in the regulation of growth hormone secretion, were measured in human milk samples. The study was performed in healthy women within 48 h of delivery or during established lactation (between 1 and 64 weeks post delivery). No statistically significant correlation was found between the levels in milk of either of the neuropeptides and the gestational age at birth. However, lower values of GRF (23 +/- 4.7 pg/ml vs. 40.5 +/- 4.9 pg/ml) were found in milk obtained during established lactation than in milk obtained close to delivery. A positive correlation was observed between somatostatin and GRF concentrations in milk. The possible involvement of milk neuropeptides in the control of growth hormone secretion in the neonate, as well as in the regulation of other physiological processes, are evaluated. PMID- 2899029 TI - Fundic, antral and pancreatic D-cell population changes following oophorectomy and sex hormone administration in guinea pigs. Experimental immunocytochemical study. AB - Twelve female guinea pigs were given estradiol and another 12 testosterone for 18 days. A third group of 15 animals underwent oophorectomy and a group of 8 animals served as controls. Gastric and pancreatic D-cells were quantitated in all four groups. Oophorectomy and androgens significantly increased and estrogens significantly decreased gastric D-cell populations. Additionally, estrogens significantly decreased D-cell population in pancreatic islets. It is concluded that the alterations in gastric and pancreatic D-cell populations, which are induced by sex hormone administration and oophorectomy, possibly reflect a hormonal adaptive attempt to restore gastric secretory functions within the normal range. PMID- 2899030 TI - Pluripotent stem cells with normal or reduced self renewal survive lethal irradiation. AB - Transfusion with 10,000 or 20,000 marrow cells resulted in 30+ days survival of 15%-50% of mice exposed to an Ld90 or LD100 or radiation. The use of congenic mice with alloenzyme markers permitted the identification of host and donor cells in the peripheral blood of transfused animals. Donor cells were present initially in all hosts. Between 55% and 92% of the animals became 100% host type by 12-24 weeks after transfusion in three separate experiments. To explore whether the temporary repopulation by donor cells was due to short-lived stem cells, the marrows of several primary hosts were transfused into secondary, lethally irradiated hosts. Some of the retransplanted primary donor and host cells persisted only temporarily. It is suggested that some of the donor stem cells in both the primary and secondary hosts had an intrinsically shortened life span. PMID- 2899031 TI - DSP-4 treatment produces abnormal tyrosine hydroxylase immunoreactive fibers in rat hippocampus. AB - DSP-4 has been used as selective toxin for central norepinephrine (NE) systems. The depletion of NE by DSP-4 is though to result from neurotoxic destruction of locus coeruleus terminals and axons. We have used tyrosine hydroxylase immunocytochemistry (TH-IR), silver stains for neural degeneration, and electron microscopy to examine the morphological effects of DSP-4 treatment on the rat hippocampus. Animals survived for either 2 or 5 weeks after DSP-4 treatment. DSP 4 depleted hippocampal norepinephrine levels to 15% of control values. Abnormally enlarged TH-IR fibers were found in the hippocampus of DSP-4-treated animals. No evidence of fiber degeneration was found following light or electron microscopic examination of the dentate hilus in DSP-4-treated animals. These data suggest that DSP-4 treatment does not destroy NE terminals, but may produce an intraneuronal lesion leading to an accumulation of TH and a depletion of norepinephrine within the terminal fields. PMID- 2899032 TI - Role of peptide substrate structure in the selective processing of peptide prohormones at basic amino acid pairs by endoproteases. AB - Three putative processing enzymes, each with defined action in a prohormone system, a 'pro-ocytocin-neurophysin convertase' from bovine neurohypophysis secretory granules, a 'Leu-enkephalin Arg6 generating enzyme' from human CSF and the endoprotease from the 'S-28 convertase' complex of rat brain cortex, were tested for their ability to hydrolyze peptides deriving from pro-ocytocin, pro enkephalin B and pro-somatostatin, respectively at pairs of basic amino acids. The observations suggest that structural parameters specified by the peptide region around the dibasic moieties govern recognition by the enzyme and define which peptide bond is hydrolyzed. PMID- 2899033 TI - Inhibition of vacuolar H+-ATPases by fusidic acid and suramin. AB - The vacuolar system of eukaryotic cells is energized by a few ATP-driven ion pumps. One of these, the H+-ATPase, plays a major role in providing the protonmotive force for several organelles, as well as maintaining the proper pH inside the organelles. Formation of the protonmotive force in organelles isolated from the vacuolar system was inhibited by fusidic acid. The inhibition results from a combination of uncoupling the proton pumping and inhibition of the H+ ATPase activity. Suramin is also a potent inhibitor of the H+-ATPase from chromaffin granules. A possible connection between these activities and inhibition of HIV infection is pointed out. PMID- 2899034 TI - Kinetic analysis of proton translocation catalyzed by F0F1 ATPase. AB - Kinetic analysis of both proton translocating and steady-state ATP hydrolytic activities catalyzed by F0F1 ATPase in submitochondrial particles were carried out over an ATP concentration range of 1-2000 microM. The results were examined in relation to the prediction based on the alternate binding change model proposed by Gresser et al. [(1982) J. Biol. Chem. 257, 12030-12038] in which energy transduction occurs only at the tri-site catalytic cycle. The present results essentially contrast with the model and rather indicate that if the alternate binding mechanism holds for the ATP hydrolytic reaction, the proton translocation should be coupled to at least both bi-site and tri-site cycles. PMID- 2899035 TI - [The level of feldsher training at feldsher-midwife centers for the hygiene instruction and education of the population]. PMID- 2899036 TI - [Somatostatinomas]. AB - Somatostatinomas are endocrine tumors which prevailing secretion is somatostatin. They are localized in the pancreas and digestive tract or not often in tissues unusually secreting somatostatin, as bronchi. Forty three cases have been described until now. The endocrine syndrome, not very specific and inconstant, is the result of the somatostatin hypersecretion. Diabetes mellitus, cholelithiasis, pancreatic exocrine insufficiency, gastric hypochlorhydria and anemia are the main symptoms of pancreatic somatostatinoma. On the other hand, they are not found in digestive tumors. Somatostatinomas often secrete other hormonal peptides which may change the clinical manifestations. Radioimmunoassay of plasma somatostatin (basal level and/or after stimulation by tolbutamid) is a more successful diagnostic test; but only immunocytochemistry of the tumor can proved the diagnosis. They a bad prognosis but are not a contra-indication to make a curative treatment; surgical resection and chemotherapy by streptozotocin and 5 FU are the two treatments. PMID- 2899038 TI - The giant common duct stone: still a hard nut to crack. PMID- 2899037 TI - Restriction-fragment-length polymorphism in insulin-receptor gene and insulin resistance in NIDDM. AB - Restriction-enzyme analysis of genomic DNA from 52 White and Hispanic nondiabetic subjects and 51 subjects with non-insulin-dependent diabetes (NIDDM) was carried out with insulin-receptor cDNA probes. A polymorphic 5.8-kilobase SstI fragment was found in 12 (23.5%) of 51 NIDDM subjects but only in 4 (7.7%) of 52 nondiabetic control subjects. This association is significant by chi 2-analysis (P less than .05). Furthermore, the nondiabetic subjects with the polymorphism were found to have hyperinsulinemia and/or nondiagnostic glucose tolerance. The polymorphism is a genetic marker for a phenotype that is neither necessary nor, by itself, sufficient for NIDDM. Nevertheless, it may indicate that insulin resistance functionally related to an insulin-receptor gene polymorphism is the proximal cause of NIDDM in at least one subset of the population. PMID- 2899039 TI - Physician assistant training and practice in geriatric medicine. PMID- 2899040 TI - [The development of a high sensitivity and high linearity fluorescence microphotometry system for distribution analysis of neurotransmitter in the brain]. AB - A new fluorescence microphotometry system was developed for analysis of the distributions and amounts of neurotransmitter and its related chemical substances in the smaller brain regions. This system can measure fluorescence intensity of 10,000 points in animal brain slices which were immunohistochemically and histochemically stained. This system mounts a photomultiplier tube of high sensitivity and high linearity to a detector; therefore, this system surpasses in quantitative capability by two figures compared with an image analyzer which uses a high-sensitivity TV camera. The high-precision step-motor scanning stage moves under the objective lens of the fluorescence microscope and analyzes the entire surface of the slice: measuring speed, 250 points/min; maximum measuring area, 76 X 52 mm. The data of fluorescence intensity and position (X and Y value) on the slice are transmitted to a computer, calculated statistically and displayed two- and three-dimensionally. In this study, immunohistochemical distribution and intensity of acetylcholine, choline acetyltransferase and acetylcholinesterase in the rat cervical spinal cord were measured. The distributions of their chemical substances are consistent with previous observations. This system is applicable to a wide range of neuroscience studies. PMID- 2899041 TI - [Adrenergic therapy of glaucoma]. PMID- 2899043 TI - [Effects of 3 topically administered beta blockers on the rabbit crystalline lens]. PMID- 2899042 TI - [Corneal sensitivity after single doses of timolol, betaxolol or placebo in persons with healthy eyes--a randomized, prospective double-blind study]. PMID- 2899045 TI - [Immunodeficiency and virus infection]. PMID- 2899046 TI - [Blood donation and HTLV-1 and HIV]. PMID- 2899044 TI - Spontaneous transmitter release at the neuromuscular junction. AB - The classical studies of Katz and co-workers have shown that nerve impulses release quanta of acetylcholine at the neuromuscular junction. This release is regulated by presynaptic calcium and accounts for the trans-synaptic transmission of nerve impulses. In resting conditions it gives rise to small spontaneous potentials, i.e. miniature endplate potentials. In addition these investigators described a spontaneous molecular leakage of acetylcholine from the motor nerve. I have studied a third type of acetylcholine release. It is a spontaneous intermittent secretion of acetylcholine which postsynaptically causes large, generally slow rising potentials. This release is unaffected by presynaptic calcium and is therefore not influenced by nerve activity. The acetylcholine responsible for these potentials comes from the same pool of transmitter as that liberated by nerve impulses. The observation that the release is blocked by drugs that prevent the accumulation of acetylcholine into synaptic vesicles indicates that the secretion originates from clusters of vesicles or large vesicle-like structures in the nerve terminal. This type of release is present at a low frequency at normal neuromuscular junctions. It is markedly accelerated whenever the calcium-dependent quantal release of acetylcholine is blocked or impaired. The drug 4-aminoquinoline selectively stimulates this release. I speculate that this type of transmitter secretion is important for the development of synaptic connexions. PMID- 2899047 TI - [Seroepidemiological and clinical studies of adult T cell leukemia in Hokkaido]. PMID- 2899048 TI - [Clinical findings of adult T cell leukemia/lymphoma in Hokkaido]. PMID- 2899050 TI - Alterations of hepatic enzyme levels and of the acinar distribution of glutamine synthetase in response to experimental liver injury in the rat. AB - Glutamine synthetase shows a striking heterogeneous distribution in normal rat liver as consistently revealed by immunohistochemistry using a specific antiserum against the rat liver enzyme or a cross-reacting antiserum. The effects of zonal liver injury induced by allylformate or CCl4 on this distribution and on the activity of glutamine synthetase as well as of enzymes with different acinar distribution were investigated. Treatment with allylformate or CCl4 at appropriate concentrations led to severe hepatocyte necrosis in the periportal and perivenous zone, respectively, as revealed by histological examination and by the levels of serum marker enzymes. Exposure to allylformate (50 to 100 microliter per kg) for less than 1 day did not change the distribution and activity of glutamine synthetase but reduced the specific activities of the urea cycle enzymes. In contrast, treatment with CCl4 (1,000 microliter per kg) strongly reduced the activity and the acinar region covered by glutamine synthetase but not, for instance, the activities of the urea cycle enzymes. These results in conjunction with the data obtained for other enzymes indicate that a short exposure to these hepatotoxins affects different enzyme activities in close accord with their preferential acinar localization. During prolonged exposure this initial response was often modified due to adaptation. In the case of glutamine synthetase, however, no adaptive appearance of glutamine synthetase in other parts of the acinus could be detected even if the cell population originally expressing this phenotype was destroyed. This extremely inflexible distribution suggests that glutamine synthetase expression is a matter of cell differentiation rather than of modulation by nutritional and hormonal factors (or their acinar gradients) as found for many other hepatic enzymes. PMID- 2899049 TI - The effect of dexamethasone and glucagon on the expression of hepatocyte plasma membrane proteins during development. AB - The regulation of different maturational processes in the liver is believed to be influenced by the hormonal system. The aim of this study was to investigate the effect of two hormones, glucagon and dexamethasone, on levels of plasma membrane proteins in rat liver cells during late fetal and early postnatal stages of development. For this purpose, 18-day-old rat fetuses and 1-day-old newborns were treated with glucagon or dexamethasone and killed at 22 days of gestation and 3, 5 and 7 days of age, respectively. Postnuclei liver membranes were isolated using a sucrose gradient method and assessed for levels of specific membrane proteins. Asialoglycoprotein receptor and 110,000 Mr glycoprotein, denoted GP 110, representing the sinusoidal and bile canalicular domains, respectively, were quantitated using the immunoblot method. Membrane enzymes alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl transferase were evaluated using enzymatic methods. The data showed that glucagon and dexamethasone have a differential effect on membrane constituents according to the stage of development. Glucagon increased the levels of membrane enzymes during the late fetal stage but had no effect on liver membrane proteins in the newborn animal. In contrast, although dexamethasone elevated GP 110 in fetal rat livers, none of the other marker proteins was significantly affected. On the other hand, in newborns dexamethasone reduced the amount of asialoglycoprotein receptor and alkaline phosphatase and leucine aminopeptidase enzyme activities but greatly augmented the level of gamma-glutamyl transferase. Thus, glucagon primarily affects plasma membrane proteins in late gestation while dexamethasone does so during the early postnatal period. The roles that these two hormones may play during ontogeny is discussed with respect to liver development. PMID- 2899052 TI - High efficiency in the attribution of parental origin of non-disjunction in trisomy 21 by both cytogenetic and molecular polymorphisms. AB - The precise origin of the supernumerary chromosome can be defined in the majority of trisomy 21 cases. This is achieved by evaluating the chromosome 21 short arm polymorphism and analysing restriction fragment length polymorphisms (RFLPs) of multiple chromosome 21 loci. We report a study on 37 Italian families with Down's syndrome. In 35 cases (94.6%) both the parental and the meiotic stage of non disjunction could be established. Knowledge of the origin of the extra chromosome 21 is a pre-requisite for investigations of genetic or environmental factors that may affect the meiotic process. PMID- 2899051 TI - Prognostic evaluation in cirrhosis. PMID- 2899053 TI - Restriction fragment length polymorphisms associated with factor VIII:C gene in Chinese. AB - Twenty-six unrelated hemophilia A and 70 unrelated normal chromosomes in 184 subjects were studied to determine the frequencies of intragenic and intergenic restriction fragment length polymorphisms associated with the factor VIII:C gene. The incidences for positive BclI and BglI polymorphic sites in the Chinese were 82% and 100%, respectively. Both were higher than in other ethnic groups, while the incidence for XbaI polymorphism was 57%, which is similar to that reported in Caucasians. Using the St14.1 probe, two polymorphic TaqI allelic systems in the DXS52 region were detectable, with heterozygous rates of 0.712 (for system I, alleles 1 to 8) and 0.495 (for system II, alpha and beta alleles), respectively. Thus, using a combination of four polymorphisms, it would be possible to offer carrier detection or prenatal diagnosis in 96% of Chinese females at risk. PMID- 2899054 TI - Chromosome localization and polymorphism of an oestrogen-inducible gene specifically expressed in some breast cancers. AB - The BCEI gene codes for a small secreted protein and is expressed in the human mammary tumour cell line MCF7 under oestrogen control and in some breast cancers. We have mapped the gene to chromosome 21 using a panel of somatic hybrid lines, and in situ hybridization has allowed a precise assignment to band 21q223. Two restriction fragment length polymorphisms (RFLP) are described that should be of use in linkage or population studies to test a possible involvement of the BCEI gene in genetic predisposition to breast cancer. This gene should also be a useful marker for the genetic and physical mapping of chromosome 21, and for a better definition of the region involved in the clinical phenotype of Downs syndrome. PMID- 2899055 TI - Prenatal diagnosis of alpha-1-antitrypsin deficiency using oligonucleotide probe analysis. AB - Prenatal diagnosis of a pregnancy at risk for alpha-1-antitrypsin deficiency was performed by oligonucleotide probe analysis using M- and Z-specific oligonucleotides. The result was confirmed by the alternative approach utilizing restriction fragment length polymorphisms. Application of oligonucleotide analysis requires only fetal tissue if proteinase inhibitor types are accurately determined within the family. Our modified protocol is easy to carry out and is practicable in all laboratories where the Southern blot procedure has been established. PMID- 2899056 TI - In vitro killing of Entamoeba histolytica trophozoites by interferon-gamma activated mouse macrophages. AB - The effect of murine interferon gamma (IFN-gamma) on macrophage activation for amoebicidal activity was examined. Peritoneal macrophages were harvested from C57BL/6 mice and preincubated with IFN-gamma and/or lipopolysaccharide (LPS). In vitro amoebicidal activity of these macrophages was determined by trypan blue exclusion test against a virulent strain of E. histolytica (IP:0682:1). It was found that in vitro amoebicidal activity was evident in macrophage monolayers treated with both IFN-gamma and LPS. Macrophages treated with IFN-gamma alone did not develop cytotoxic activity unless they were exposed to LPS as a second triggering signal. The ability of IFN-gamma to prime macrophages to respond to trigger signals of LPS and develop cytotoxicity increased with time of incubation, the highest response being observed after 24 h. There was a dose dependent relationship between the concentrations of both IFN-gamma and LPS used to activate macrophages and the number of dead trophozoites. These data suggest that macrophages are important in host defense against amoebiasis. PMID- 2899057 TI - Studies on the adjuvant action of beryllium. IV. The preparation of beryllium containing macromolecules that induce immunoblast responses in vivo. AB - Solutions of BeSO4 were added to soluble macromolecules and the mixtures brought to neutrality. Under appropriate conditions much of the beryllium did not precipitate out as insoluble hydroxides but became attached to naturally occurring sulphated proteoglycans and polysaccharides (e.g. heparin, chondroitin sulphate, fucoidan, etc.) and to synthetic, sulphonated aromatic dyestuffs (e.g. trypan, Evans and Coomassie blues, Suramin, etc.). At physiological conditions of pH and ionic strength, these addition compounds were relatively stable and did not dissociate during dialysis. When such materials were injected s.c. into sheep (in doses containing about 50 micrograms Be), rapid lymphoproliferative responses took place in the regional nodes so that immunoblasts appeared in the efferent lymph in numbers that exceeded those provoked by powerful conventional antigenic stimuli. Significant amounts of the injected materials passed through the nodes and, in intact animals, became systematized. A method was devised for attaching beryllium to particulate carriers, such as lymphocytes or red cells that had been fixed with glutaraldehyde. The injection of suspensions of such materials also provoked vigorous immunoblastic responses, but the particulate materials did not pass beyond the regional node. In the doses usually used, none of these materials was grossly toxic and they may be suitable for consideration for development into a new type of immunostimulator cum adjuvant. PMID- 2899058 TI - Role of the nucleus ambiguus in the regulation of heart rate and arterial pressure. AB - The present study examined the effect of lesion of cell bodies in the nucleus ambiguus area on the development of neurogenic hypertension and further explored the cardiovascular responses produced by chemical and electrical stimulation of the nucleus ambiguus and the neighboring C1 region. Three days after chemical lesion of the nucleus ambiguus with kainic acid, arterial pressure and heart rate were unchanged; however, subsequent sinoaortic deafferentation produced a significantly greater increase of arterial pressure (157 +/- 7 vs 132 +/- 5 mm Hg) and heart rate (436 +/- 10 vs 374 +/- 10 beats/min) compared with those produced by sham lesion. Glutamate injected into the nucleus ambiguus increased arterial pressure and heart rate at 20 nmol/100 nl and decreased heart rate at 50 nmol/100 nl. Glutamate injected into the C1 area increased arterial pressure and heart rate at both doses. Gamma-Aminobutyric acid at 50 nmol/100 nl produced bradycardia and a fall in arterial pressure when injected into both the nucleus ambiguus and C1 area. The heart rate responses to gamma-aminobutyric acid and glutamate were attenuated in sinoaortic-deafferentated rats. The nucleus ambiguus and the C1 region were mapped using electrical stimulation with microelectrodes. All points stimulated in three anteroposterior sections in the nucleus ambiguus and the C1 area produced increases in arterial pressure, whereas bradycardia was restricted to the middle of three lateral coordinates associated with the center of the nucleus ambiguus and the C1 area ventral to the nucleus ambiguus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899059 TI - Vascular and sympathoadrenal responses to bradykinin and a bradykinin analogue. AB - These experiments were designed to assess the interaction of bradykinin and its antagonist (Arg-Pro-Hyp-Gly-Phe-Ser-DPhe-Phe-Arg-trifluoroacetic acid) with the sympathoadrenal system. Three groups of male Wistar rats received 5-minute intra arterial infusions of either dextrose (Group 1, n = 6), bradykinin, 250 micrograms/min (Group 2, n = 5), or bradykinin, 25 micrograms/min (Group 3, n = 4). Six other groups received a similar infusion of the bradykinin antagonist at 250 micrograms/min. They were either intact rats (Group 4, n = 10) or rats previously submitted to chemical sympathectomy (Group 5, n = 17), to adrenal enucleation (Group 6, n = 8), to combined alpha-adrenergic and beta-adrenergic blockade (Group 7, n = 7), to alpha 1-adrenergic receptor blockade (Group 8, n = 8), or to alpha 2-adrenergic receptor blockade (Group 9, n = 8). Bradykinin infusion produced a sustained fall in mean arterial pressure (MAP) in Groups 2 and 3 (by -48 +/- 3 and -36 +/- 7 mm Hg, respectively) associated with similar increases in plasma epinephrine levels (100-fold), and norepinephrine (sevenfold) as compared with Group 1. The bradykinin antagonist infusion in intact rats produced a 23 +/- 4 mm Hg rise in MAP associated with a sixfold increase in epinephrine and a twofold increase in norepinephrine. Group 5 rats with lower baseline catecholamine levels had an even larger MAP rise (30 +/- 6 mm Hg) accompanied by a rise in epinephrine and norepinephrine proportionally similar to that of intact animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899060 TI - Geographic distribution of HTLV-I and identification of a new high-risk population. AB - Epidemiologic studies indicate that human T-cell lymphotropic virus type I (HTLV I), the causative agent of most cases of adult T-cell leukemia/lymphoma (ATLL) in Southeast Japan and the Caribbean islands and the probable cause of a progressive neurological disorder often referred to as tropical spastic paraparesis, occurs with unusual geographic clustering. The current large-scale serosurvey was undertaken to improve our understanding of HTLV-I prevalence in different parts of the world. We analyzed 43,445 serum samples collected from various geographic locales worldwide; 76% of these sera came from clinically healthy donors. Samples were initially screened by an enzyme-linked immunosorbent assay (ELISA) and 4,353 were further evaluated by means of competition assays. In this study, which did not include sera from endemic areas of Japan, a high prevalence of infection was observed in several countries in the Caribbean basin. A significant age-sex difference was observed between populations in the Caribbean and non-endemic regions of Japan. The reason for the male excess in non-endemic areas of Japan will require further study, while the female excess in the Caribbean basin is compatible with the previously described pattern for other HTLV-I-endemic areas. A newly recognized area of possible endemicity was southern Florida, where evidence of infection with HTLV-I or a related virus was found in a group of native Americans whose sera were collected in 1968. In certain parts of the world, particularly sub-Saharan Africa, important problems in determining specificity of reactivity occurred, probably because of cross-reacting antibodies. No pattern was detected that could explain the cross-reactivity solely on the basis of geographic areas, specific patterns of non-viral parasitic infection, or methods of handling the specimens. It is possible that these cross reactivities are antibodies to proteins from HTLV-I-related retroviruses yet to be discovered. PMID- 2899061 TI - Edmund Lesser and the International Congress of Dermatology. PMID- 2899063 TI - Beyond the bottom line. PMID- 2899062 TI - Comparison of thermogenic activity induced by the new sympathomimetic Ro 16-8714 between normal and obese subjects. AB - In a previous study, we demonstrated that the new beta-adrenoceptor agonist Ro 16 8714 possesses thermogenic property in normal male volunteers. The aim of the present study was to compare the metabolic response of lean vs obese individuals to a similar dose of this compound. Following an overnight fast, Ro 16-8714 (0.17 mg/kg fat free mass) or a placebo was given per os to six normal-weight subjects and to six moderately obese subjects. The rate of energy expenditure (EE) and the substrate utilization were determined by indirect calorimetry (hood system) before and for 6 h following the drug administration. Heart rate and blood pressure as well as plasma glucose, insulin and free fatty acid (FFA) concentrations were also measured at regular intervals throughout the study. The increment relative to base-line (mean +/- s.e.m.) in EE was similar in the two groups and averaged 4.0 +/- 1.4 per cent and 12.2 +/- 1.4 per cent with placebo and with Ro 16-8714 respectively in lean subjects, whereas the values reached 3.5 +/- 1.2 per cent and 14.4 +/- 2.0 per cent in obese subjects. Heart rate, systolic blood pressure, insulin and FFA were increased without any significant difference between the two groups. This study shows that Ro 16-8714 is a potent thermogenic agent both in normal and obese subjects. PMID- 2899064 TI - Aging: a new fad. PMID- 2899065 TI - A case for a tickler file. Will you renew your contract or will it renew itself? PMID- 2899067 TI - Clinicopathologic correlations of eighty nonpalpable breast lesions. PMID- 2899066 TI - Balloon dilatation for mitral stenosis. PMID- 2899068 TI - Dorothea Lynde Dix. A pioneer in mental health care. PMID- 2899069 TI - Go West young man! Correspondence from an Illinois frontier physician. By Orlando M. Bryan. Sycamore, January 26, 1847. PMID- 2899071 TI - Neuroleptic-induced supersensitivity psychosis: retrospective study of schizophrenic inpatients. AB - Chouinard has suggested that a significant number of schizophrenic outpatients may rapidly relapse after discontinuing or abruptly reducing antipsychotic drugs, and he has hypothesized that this relapse reflects a supersensitivity psychosis related to mesolimbic postsynaptic dopamine supersensitivity caused by drug therapy. Using Chouinard's criteria, the authors found 12 probable but no definitive cases of this syndrome while conducting a chart review of 265 hospitalized schizophrenic patients. Six of the 12 patients were subsequently rediagnosed as schizoaffective. Four patients had tardive dyskinesia, but this condition did not worsen after the drug dosage was decreased. Although supersensitivity psychosis was not common among this population, further study of the syndrome is needed to determine if neuroleptics are causing a subgroup of patients to relapse early or if the early relapses are a manifestation of the natural course of illness in these patients. PMID- 2899070 TI - Primary liver cell cultures grown on gas permeable membrane as source for the collection of primary bile. AB - Isolated rat hepatocytes maintained in primary culture on gas permeable membrane for 20 h form monolayers and establish at their cell borders a network of canaliculi (approximate diameter 3.5 micron). In the presence of the known choleretic bile acid dehydrocholate, dilation of canaliculi occurs. When nonfluorescent carboxyfluorescein diacetate ester is added to the culture medium, fluorescent carboxyfluorescein appears in the intracanalicular space. In the dilated state, fluid containing the fluorescent compound could be collected from the canaliculi by puncture with a micropipette. The intracanalicular space shows a negative electrical potential difference of 31 mV in reference to the bath solution and is 13.5 mV more positive with reference to recordings from the cytosol of cultured rat hepatocytes. Cultured rat hepatocytes grown on gas permeable membrane are energetically stable over 3 d. On Day 4, ATP levels increase markedly, whereas Na+-K+-ATPase activity declines. Ionic composition of hepatocytes, as measured by electronprobe element analysis on cryosection samples, does not change markedly during monolayer formation. With formation of bile canaliculi, the activity of alkaline phosphatase rapidly increases within 24 h and is stable for the next 3 d. Within that time the activity of gamma glutamyltranspeptidase, however, increases steadily, reaching a 1.6-fold higher activity than freshly isolated hepatocytes. Bile acids appear in the culture supernatant after 1 d. When unconjugated [14C]cholic acid is added to the cultures the supernatant contains also [14C]tauro- and [14C]glycocholic acid, indicating the preservation of conjugation capacity in these cultures. Total bile acid concentrations in the supernatant increase from 5 to 26 microM on Day 4. The cultures do not secrete alpha-fetoprotein. Monolayer cultures of hepatocytes in the presence of choleretic bile acids seem to be a suitable model system to collect and to analyze the composition of primary bile. In conjunction with the electrical parameters, it is possible to describe directly properties of bile secretion at the canalicular pole of the intact hepatocyte. PMID- 2899072 TI - Membrane-bound trypsin-like enzyme functioning in degradation of dynorphin in neuroblastoma cells. Purification and characterization. AB - A trypsin-like enzyme has been purified to apparent homogeneity from neuroblastoma cell membranes by a procedure including extraction with Triton X 100, soybean trypsin inhibitor-immobilized Sepharose 4B affinity chromatography, and gel filtration. SDS-polyacrylamide gel electrophoresis under reducing conditions of the purified enzyme gave a single band corresponding to a molecular weight of 28,000. The molecular weight of the enzyme was also estimated to be 32,000 by gel filtration. The pH optimum of the activity was 8.5-9.0. The purified enzyme was inhibited by diisopropylphosphorofluoridate, p aminobenzamidine, and leupeptin, and moderately by chymostatin, but not, or only scarcely, by bestatin, phosphoramidon, p-chloromercuribenzoate, and N ethylmaleimide. The substrate subsite specificity of the purified enzyme was broad toward various peptidyl-arginine (or lysine) 4-methylcoumaryl-7-amides, but it cleaved dynorphin(1-17) only at two sites, i.e., between the Arg6-Arg7 and Lys11-Leu12 bonds, both of which correspond to the initial cleavage sites of dynorphin with a membrane preparation of neuroblastoma cells. A trypsin-like enzyme was also purified from a synaptic membrane preparation of rat brain, which shows almost the same properties as those of the enzyme from the neuroblastoma cell membrane. Thus, the trypsin-like enzyme present in the synaptic membrane would participate in the degradation of dynorphin. PMID- 2899073 TI - Intrinsic membrane sector (Fo) of H+-ATPase (FoF1) from Escherichia coli. Mutations in the alpha subunit give Fo with impaired proton translocation and F1 binding. AB - Mutant alleles for the alpha subunit of H+-translocating ATPase (FoF1) were cloned from Escherichia coli strains isolated in this laboratory. Determination of their DNA sequence revealed four nonsense mutations (KF3 and KF9, Gln-20--- end; KF24, Trp-111----end; KF2, Trp-231----end; KF70, Gln-252----end) and one missense mutation (KF45, Pro-143----Ser). The membranes of all the mutants except strain KF9 (KF3) had 50-70% of ATPase activities of the wild-type. Unlike the F1 ATPase of the wild-type, those of the mutants were insensitive to dicyclohexylcarbodiimide and were easier to solubilize from membranes. As membranes of strain KF24 had F1-ATPase activity, these results suggest that at least a part of the F1-binding sites could be formed without a region between residues 111 and the carboxyl terminus of the alpha subunit. However, normal interactions between Fo and F1 require regions between residues 252 and 271 (carboxyl terminus) and in the vicinity of Pro-143. Membranes of strain KF45 were capable of forming a low ATP-driven H+ gradient, whereas other membranes were not. The possibility that the region between residues 252 and 271 is involved in H+ translocation is discussed. PMID- 2899074 TI - Isoprenoid synthesis during the cell cycle. Studies of 3-hydroxy-3-methylglutaryl coenzyme A synthase and reductase and isoprenoid labeling in cells synchronized by centrifugal elutriation. AB - The activities of 3-hydroxy-3-methylglutaryl-coenzyme A synthase and reductase were assayed in exponentially growing LM fibroblasts and Friend murine erythroleukemia cells isolated at various stages of the cell cycle by centrifugal elutriation. The activities of these enzymes were similar in all phases of the cell cycle, regardless of whether the cells were cultured in the presence or absence of serum. These observations were confirmed in murine erythroleukemia cells synchronized by recultivation of pure populations of G1 cells. The incorporation of [14C]acetate or 3H2O into sterols decreased by 30-50% in later stages of the cell cycle, whereas the incorporation of [14C]acetate into ubiquinone increased as the cells progressed toward mitosis. Similar changes in the labeling of sterols compared to ubiquinone and dolichol were observed when [3H]mevalonate was used, suggesting that cell cycle-dependent alterations may occur in the flux of farnesyl pyrophosphate into the various branches of the isoprenoid pathway. Synchronized murine erythroleukemia cells incorporated [3H]mevalonate into protein-bound isoprenyl groups at all stages of the cell cycle, and there were no substantial changes in the electrophoretic profiles of these labeled polypeptides. The finding that the activities of the enzymes regulating mevalonate synthesis did not vary substantially during the cell cycle implies that changes in the endogenous mevalonate pool probably do not play a limiting role in regulating cell cycle traverse when cells are undergoing exponential growth. Although small cell cycle-dependent changes may occur in the relative activity of various post-mevalonate branches of the isoprenoid biosynthetic pathway, there is no evidence that synthesis of any major isoprenoid end product is confined exclusively to a specific phase of the cell cycle. PMID- 2899075 TI - Regulation of the proliferating cell nuclear antigen cyclin and thymidine kinase mRNA levels by growth factors. AB - The enzymes of the DNA synthesizing machinery constitute a group of gene products that are generally expressed co-ordinately at the G1/S boundary of the cell cycle. We have investigated how growth factors regulate the steady-state mRNA levels of two of these genes, the PCNA (proliferating cell nuclear antigen)/cyclin and the thymidine kinase genes. To detect the PCNA/cyclin mRNA, we isolated a cDNA clone from a human library. Two different cell lines were used for these studies: BALB/c3T3 cells, which are exquisitely sensitive to growth factors, and ts13 cells, a temperature-sensitive (ts) mutant of the cell cycle, which arrests in G1 at the restrictive temperature. The steady-state levels of the RNAs for these two genes under different growth conditions were also compared with the levels of histone H3 RNA which are good indicators of the fraction of cells in S phase. Both PCNA/cyclin and thymidine kinase genes share two fundamental characteristics, i.e. they are not inducible in a G1-specific ts mutant of the cell cycle at the restrictive temperature and their expression is inhibited by cycloheximide, indicating that unlike early growth-regulated genes, they require the previous expression of other growth-regulated genes. However, the two genes also show differences, the most notable being that PCNA/cyclin is inducible by epidermal growth factor alone, while thymidine kinase is not. PMID- 2899077 TI - Factor XIII cross-linking of fibronectin at cellular matrix assembly sites. AB - We describe the effect of activated Factor XIII (Factor XIIIa, plasma transglutaminase) on the incorporation of plasma fibronectin into extracellular matrix by cultured human fibroblasts. In the absence of added Factor XIIIa, fibronectin binds to cultured fibroblast cell layers and is assembled into disulfide-bonded multimers of the extracellular matrix. When Factor XIIIa was included in the binding medium of skin fibroblasts, accumulation of 125I fibronectin in the deoxycholate-insoluble matrix was increased. Fibronectin accumulating in the cell layer was cross-linked into nonreducible high molecular weight aggregates. The 70-kDa amino-terminal fragment of fibronectin inhibited the binding and cross-linking of 125I-fibronectin to cell layers, whereas fibrinogen had little effect. When 125I-fibronectin was incubated with isolated matrices or with cell layers pretreated with cytochalasin B, it did not bind and could not be cross-linked by Factor XIIIa into the matrix. HT-1080 human fibrosarcoma cells bound exogenous fibronectin following treatment with dexamethasone; Factor XIIIa cross-linked the bound fibronectin and caused its efficient transfer to the deoxycholate-insoluble matrix. These results indicate that exogenous fibronectin is susceptible to Factor XIIIa-catalyzed cross-linking at cellular sites of matrix assembly. Thus, Factor XIIIa-mediated fibronectin cross-linking complements disulfide-bonded multimer formation in the stabilization of assembling fibronectin molecules and thus enhances the formation of extracellular matrix. PMID- 2899076 TI - Conserved aspartic acid residues 79 and 113 of the beta-adrenergic receptor have different roles in receptor function. AB - Deletion mutagenesis experiments have demonstrated that the binding site of the beta-adrenergic receptor involves the hydrophobic core of the protein (Dixon, R. A. F., Sigal, I. S., Rands, E., Register, R. B., Candelore, M. R., Blake, A. D., and Strader, C. D. (1987) Nature 326, 73-77). Single amino acid replacements for the conserved Asp79 and Asp113 within this putative transmembrane region had profound effects on the ability of the receptor to bind radiolabeled ligands (Strader, C. D., Sigal, I. S., Register, R. B., Candelore, M. R., Rands, E., and Dixon, R. A. F. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 4384-4388). In this report we have analyzed the ability of these mutant receptors to stimulate adenylyl cyclase in the presence of agonists. The substitution of Asp79 with Ala caused 10-fold increases in both the Kd for isoproterenol binding and the Kact for adenylyl cyclase stimulation. The substitution of Asp113 by Asn or Glu resulted in 8,000-40,000 and 300-1,500-fold increases, respectively, in the Kact values for agonist stimulation of adenylyl cyclase without altering the maximum level of stimulation. Whereas the binding of antagonists to the receptor was not affected by substitution of Asp79, substitution of Asp113 decreased the affinity for the antagonist propranolol by 10,000-fold. These data are consistent with overlapping but not identical binding sites for agonists and antagonists on the beta-adrenergic receptor, in which the carboxylate group of Asp113 interacts with the amino group of the ligand. The sequence similarity among the family of G protein-linked receptors suggests that the presence of an Asp residue at the analogous position of one of these receptors is predictive of the ability of the receptor to bind amines as ligands. PMID- 2899078 TI - Characterization of a protein serine kinase from yeast plasma membrane. AB - A casein kinase activity, which copurifies with the H+-ATPase activity during isolation of plasma membranes Saccharomyces cerevisiae and during centrifugation of the solubilized membrane extract through a sucrose gradient, is separated from the Mr = 100,000 ATPase catalytic polypeptide by subsequent DEAE-cellulose chromatography. The purified casein kinase activity exhibits a low Km of 12 microM MgATP, is maximally stimulated by 6 mM free Mg2+, and is 50% inhibited by 300 microM Zn2+, by 7.5 micrograms of heparin/ml, and by 300 microM orthovanadate. It phosphorylates only seryl residues. The purified casein kinase contains two polypeptides of Mr = 45,000 and 39,000 which yield antibodies which do not cross-react to each other. The two polypeptides seem to originate from a precursor of Mr = 85,000 which is detected by both antibodies in partly purified fractions. In the absence of casein, a zinc and heparin-sensitive phosphorylation of the ATPase polypeptide is observed in partly purified ATPase fractions, and a peptide of similar mobility is phosphorylated, among others, in isolated plasma membranes. The purified ATPase activity is markedly inhibited by incubation in the presence of acid phosphatase. In agreement with a recent report that the purified active ATPase molecule is largely phosphorylated (Yanagita, Y., Abdel Ghany, M., Raden, D., Nelson, N., and Racker, E. (1987) Proc. Natl. Acad. Sci. U. S. A. 894, 925-929) this data suggests that dephosphorylation leads to deactivation of ATPase activity. PMID- 2899079 TI - Sequence and characterization of two auxin-regulated genes from soybean. AB - The auxin-regulated expression of two poly(A)+ mRNAs in soybean hypocotyl was demonstrated by cloning of the cDNAs and Northern blot hybridization analyses (Walker, J.C., and Key, J.L. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 7185-7189). The corresponding genes, designated Aux28 and Aux22, have been isolated, and the cDNAs and genes have been sequenced. The Aux28 and Aux22 genes are present at one to two copies per haploid genome, contain four and two introns, and encode hydrophilic proteins of 26.8 and 21.5 kDa, respectively. Although the cDNAs were isolated independently and do not cross-hybridize under stringent hybridization conditions, the protein coding sequences of the two cDNAs have several colinear regions of high homology at the nucleic acid (77-80%) and the amino acid (80 100%) levels; together these regions constitute approximately a third of the protein coding sequences of the cDNAs. These data, together with genomic Southern blot hybridization analysis and hybrid-select translations of mRNAs homologous to the cDNAs, show that these genes belong to two related multigene families. We have identified two sequences, TGATAAAAG and GGCAGCATGCA, that occur at similar distances upstream of the transcription start site in each gene, and the spacing between these two elements is essentially identical in the two genes. The possible significance of these sequences is under evaluation. PMID- 2899080 TI - Regulation of malate dehydrogenase activity by glutamate, citrate, alpha ketoglutarate, and multienzyme interaction. AB - Binding experiments indicate that mitochondrial aspartate aminotransferase can associate with the alpha-ketoglutarate dehydrogenase complex and that mitochondrial malate dehydrogenase can associate with this binary complex to form a ternary complex. Formation of this ternary complex enables low levels of the alpha-ketoglutarate dehydrogenase complex, in the presence of the aminotransferase, to reverse inhibition of malate oxidation by glutamate. Thus, glutamate can react with the aminotransferase in this complex without glutamate inhibiting production of oxalacetate by the malate dehydrogenase in the complex. The conversion of glutamate to alpha-ketoglutarate could also be facilitated because in the trienzyme complex, oxalacetate might be directly transferred from malate dehydrogenase to the aminotransferase. In addition, association of malate dehydrogenase with these other two enzymes enhances malate dehydrogenase activity due to a marked decrease in the Km of malate. The potential ability of the aminotransferase to transfer directly alpha-ketoglutarate to the alpha ketoglutarate dehydrogenase complex in this multienzyme system plus the ability of succinyl-CoA, a product of this transfer, to inhibit citrate synthase could play a role in preventing alpha-ketoglutarate and citrate from accumulating in high levels. This would maintain the catalytic activity of the multienzyme system because alpha-ketoglutarate and citrate allosterically inhibit malate dehydrogenase and dissociate this enzyme from the multienzyme system. In addition, citrate also competitively inhibits fumarase. Consequently, when the levels of alpha-ketoglutarate and citrate are high and the multienzyme system is not required to convert glutamate to alpha-ketoglutarate, it is inactive. However, control by citrate would be expected to be absent in rapidly dividing tumors which characteristically have low mitochondrial levels of citrate. PMID- 2899081 TI - Heterodimeric transforming growth factor beta. Biological properties and interaction with three types of cell surface receptors. AB - Type beta transforming growth factors (TGF) are disulfide-linked homo- and heterodimers of two related polypeptide chains, beta 1 and beta 2. The homodimers TGF-beta 1 and TGF-beta 2 are widely distributed, but the heterodimer TGF-beta 1.2 has been found only in porcine platelets (Cheifetz, S., Weatherbee, J.A., Tsang, M.L.-S., Anderson, J.K., Mole, J.E., Lucas, R., and Massague, J. (1987) Cell 48, 409-415). Here we characterize the receptor binding and biological properties of TGF-beta 1.2 and compare them with those of TGF-beta 1 and TGF-beta 2. Three types of cell surface receptors previously identified by affinity labeling with 125I-TGF-beta 1 are available for binding to TGF-beta 1.2. These three types of receptors are detected as 65-kDa (type I), 85-95-kDa (type II), and 250-350-kDa (type III) affinity-labeled receptor complexes on electrophoresis gels. They co-exist in many cell types, have high affinity for TGF-beta 1, and varying degrees of affinity for TGF-beta 2. Of the 11 cell lines screened in the present study none showed evidence for additional receptor types that would bind TGF-beta 2 but not TGF-beta 1. In receptor competition studies, TGF-beta 1, TGF beta 1.2, and TGF-beta 2 competed for binding to type I and type II receptors with a relative order of potencies of 16:5:1 and 12:3:1, respectively, whereas all three forms of TGF-beta were equipotent as ligands for the type III receptors. The three forms of TGF-beta were equally potent at stimulating the biosynthesis of extracellular sulfated proteoglycan in BRL-3A rat liver epithelial cells, a response that presumably involves the type III receptor present in these cells. In contrast, the ability of the three ligands to inhibit the growth of B6SUt-A multipotential hematopoietic progenitor cells which display only type I receptors decreased in the order TGF-beta 1, TGF-beta 1.2, and TGF beta 2 with a relative potency of 100:30:1. The results indicate that the presence of one beta 1 chain in TGF-beta 1.2 increases (with respect to TGF-beta 2) the biological potency and binding affinity toward receptor types I and II, but the presence of a second beta 1 chain in the dimer is required for full potency. PMID- 2899082 TI - A linear analog of atrial natriuretic peptide (ANP) discriminates guanylate cyclase-coupled ANP receptors from non-coupled receptors. AB - Atrial natriuretic peptide (ANP) contains a disulfide which is generally considered to be required for biological activity. A truncated linear ANP analog, des-Cys105,Cys121-ANP-(104-126) (referred to as analog I), that lacks the 2 cysteine residues of the parent peptide was synthesized. In competition binding studies using rabbit lung membranes, ANP-(103-126) and analog I displaced bound 125I-ANP-(103-126) from specific ANP binding sites 100 and 73%, respectively. The concentrations of ANP-(103-126) and analog I that produced 50% inhibition of radioligand binding to the membranes were 0.26 +/- 0.07 and 0.31 +/- 0.09 nM, respectively. Radioiodinated ANP-(103-126) and analog I were chemically cross linked to binding sites on rabbit lung membranes, and the labeled membrane proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. 125I-Analog I specifically labeled a 65,000 dalton protein and a 135,000-dalton protein which, under reducing conditions, dissociated into 65,000-dalton subunits. In contrast, 125I-ANP-(103-126) labeled specifically a nonreducible 135,000-dalton protein, in addition to the 65,000 dalton species and the reducible 135,000-dalton species. ANP-(103-126) (100 nM) stimulated rabbit lung particulate guanylate cyclase activity, whereas analog I, at the same concentration, had no effect on cyclic GMP production and did not antagonize the effect of ANP-(103-126). From these observations, we conclude that analog I is a selective ligand which binds to approximately 73% of the total ANP binding sites present in rabbit lung membranes. Unlike ANP-(103-126), analog I does not bind to the remaining 27% of the binding sites and does not activate guanylate cyclase. Binding to the cyclase-linked ANP receptor correlates with the specific labeling by 125I-ANP-(103-126) of the nonreducible 135,000-dalton membrane protein. PMID- 2899083 TI - Comparison of the effects of NGF, activators of protein kinase C, and a calcium ionophore on the expression of Thy-1 and N-CAM in PC12 cell cultures. AB - The addition of nerve growth factor (NGF) to PC12 cells induces an approximate doubling in the cell surface expression of the Thy-1 glycoprotein and the neural cell adhesion molecule (N-CAM) after 24 h of culture. Although both responses are measured at the same time point, their sensitivity to NGF differed with half maximal induction of Thy-1 apparent at NGF concentrations (approximately 0.1 ng/ml NGF) that had little effect on N-CAM expression. Phorbol ester derivatives capable of activating Ca2+/phospholipid-dependent protein kinase (protein kinase C) and the calcium ionophore A23187 were found to mimic the NGF induction of Thy 1, but not N-CAM. Similar results were observed when a synthetic diacylglycerol was added to PC12 cell cultures. Increased expression of Thy-1 consequent to phorbol ester, calcium ionophore, or NGF treatment was associated with an increase in the expression of the mRNA species that encodes Thy-1. Increased expression of Thy-1 consequent to all three treatments was also reduced by treatment with the transcription inhibitor cordycepin. Treatment of PC12 cells with high concentrations of phorbol esters was found to inhibit the NGF induction of Thy-1, but not N-CAM. Whereas the above results are consistent with activation of protein kinase C underlying the NGF induction of Thy-1, the same data are not consistent with this pathway being important in the N-CAM response. PMID- 2899084 TI - [The role of surgery in the treatment of duodenal ulcer]. AB - If duodenal ulcer surgery has been limited since introduction of anti-H2, it keeps an important position. For chronic duodenal ulcer, surgery currently represent a reasonable alternative to medical treatment, owing to two operations, fundic vagotomy and more recently anterior lesser curve sero-myotomy + posterior truncal vagotomy; the permanent effect of surgery contrast with the only suspensive effect of medical treatment on ulcer disease. For ulcer complications, surgery is often mandatory, but in emergency, truncal vagotomy + drainage keeps a predominant position. PMID- 2899085 TI - The new genetics and clinical medicine: a summing up. PMID- 2899086 TI - Assay of gamma-L-glutamylcyclotransferase activity in rat brain synaptosomes by high-performance liquid chromatography. PMID- 2899087 TI - Rapid and sensitive high-performance liquid chromatographic determination of bisoprolol in plasma and urine. PMID- 2899088 TI - Inhibition of thyrotropin-stimulated iodide uptake in FRTL-5 thyroid cells by crude immunoglobulin fractions from patients with goitrous and atrophic autoimmune thyroiditis. AB - We studied the effects of crude immunoglobulin (Ig) fractions of serum from patients with goitrous and atrophic autoimmune thyroiditis on TSH-, thyroid stimulating immunoglobulin (TSI)-, forskolin-, and dibutyryl cAMP-stimulated 125I uptake by FRTL-5 thyroid cells. TSH-stimulated 125I uptake was inhibited by the Ig fractions from 15 patients with atrophic thyroiditis who had serum TSH binding inhibitor Igs (TBII), 10 (62.5%) of 16 TBII-negative patients with atrophic thyroiditis, 7 (43.8%) of 16 hypothyroid patients with goitrous thyroiditis who had no TBII activity, and only 2 (15.4%) of 13 euthyroid patients with goitrous thyroiditis who were negative for TBII. The mean inhibition of TSH-stimulated 125I uptake produced by the crude Igs from the former 3 groups of hypothyroid patients was statistically significant (P less than 0.001, P less than 0.001, and P less than 0.01, respectively) and correlated closely with the ability of the Ig fractions to inhibit TSI-stimulated 125I uptake (r = 0.882) and TSH-stimulated cAMP accumulation (r = 0.929). The inhibition of TSH- or TSI-stimulated 125I uptake by Ig samples containing TBII correlated significantly with the TBII activities. On the other hand, in the presence of Igs from TBII-negative hypothyroid patients, the inhibition of TSH-stimulated 125I uptake correlated significantly with that of forskolin-stimulated 125I uptake (r = 0.685). Although 6 (12.8%) of 47 Ig samples from hypothyroid patients inhibited dibutyryl cAMP stimulated 125I uptake, the activities were marginal. These findings suggest that at least 2 types of antibodies are involved in the inhibition of TSH- or TSI stimulated 125I uptake: 1 being a competitive inhibitor of TSH binding to its receptors, and another exerting influence on a step subsequent to TSH or TSI binding, presumably through adenylate cyclase inhibition. PMID- 2899089 TI - Medical management of acromegaly due to ectopic production of growth hormone releasing hormone by a carcinoid tumor. AB - A 59-yr-old woman with a disseminated carcinoid tumor was evaluated for acromegaly. She had previously undergone a hypophysectomy for acromegaly and an enlarged pituitary, with a reduction in her serum GH levels from 100 to 4 micrograms/L. Recurrence of acromegalic symptoms 2 yr later was accompanied by elevated serum GH (16 micrograms/L) and insulin-like growth factor I (IGF-I; 528 micrograms/L) and plasma GHRH levels (12 micrograms/L; normal, less than 30 ng/L). Computed tomographic scan did not reveal pituitary enlargement. Metastatic carcinoid tissue in bone removed at biopsy contained GHRH (100 pg/mg tissue). High performance liquid chromatography of plasma GHRH revealed predominantly GHRH (3-40)-OH, a biologically inactive GHRH metabolite, along with mature GHRH forms, while carcinoid tissue contained both GHRH-(1-40)-OH and GHRH-(1-44)-NH2. Treatment with pergolide initially resulted in reduction in serum GH and IGF-I levels and amelioration of symptoms of acromegaly. However, after 14 months of pergolide therapy, serum GH levels increased despite administration of up to 1000 micrograms pergolide/day. Plasma GHRH levels remained elevated throughout the treatment period. Subsequent treatment with SMS 201-995, a long-acting somatostatin analog, for over 1 yr resulted in sustained reductions of ectopic GHRH secretion, GH hypersecretion, and IGF-I levels. Plasma GHRH levels correlated with simultaneously measured serum GH levels in response to acute SMS 201-995 administration. SMS 201-995 was an effective medical treatment for acromegaly caused by ectopic GHRH production in this patient. PMID- 2899090 TI - Somatostatin enhances insulin-mediated glucose disposal in elderly subjects. AB - Somatostatin (SRIH) infusion has been widely used in metabolic studies of carbohydrate metabolism. While the effects of SRIH itself on various aspects of carbohydrate economy have been assessed in young adults, such studies have not been conducted in the elderly, which represent an increasingly important study group. To examine the effect of SRIH on insulin-mediated glucose disposal in the elderly, we studied 12 (7 men and 5 women) healthy nonobese subjects, aged 65-80 yr. Paired 3-h euglycemic insulin clamp studies were performed in random order employing insulin alone (22 mU/m2.min) or insulin with SRIH (250 micrograms/h) and glucagon (0.4 ng/kg.min) to maintain normal basal plasma glucagon levels. Basal plasma insulin, glucose, glucagon, GH, and glucose production and disappearance were similar on each occasion. Steady state (10-180 min) mean plasma insulin [insulin alone, 298 +/- 12 (+/- SE); insulin; glucagon, and SRIH, 304 +/- 15 pmol/L] and glucagon (insulin alone, 85 +/- 7; insulin, glucagon, and SRIH, 96 +/- 9 ng/L) concentrations were similar. At steady state (150-180 min) glucose production was suppressed to similar levels (insulin alone, 26 +/- 7; insulin, glucagon, and SRIH, 36 +/- 13 mumol/kg.min). However, steady state glucose disposal was significantly higher during the SRIH infusion (insulin alone, 295 +/- 26; insulin, glucagon, and SRIH, 346 +/- 32 mumol/kg.min; P less than 0.02). We conclude that SRIH augments insulin-mediated glucose disposal in healthy older subjects at physiological levels of insulin. PMID- 2899091 TI - Myogenic and neurogenic regulation of myosin gene expression in cat jaw-closing muscles regenerating in fast and slow limb muscle beds. AB - Immunocytochemical techniques were used to study changes in myosin gene expression during the regeneration of the cat posterior temporalis muscle transplanted into the bed of either the fast extensor digitorum longus (EDL) or the slow soleus muscle. Strips of the posterior temporalis, a homogeneously superfast muscle, were treated with Marcaine and then transplanted into limb muscle beds which had been completely cleared of host muscle fibres. The regenerates were examined 6 to 224 days after surgery. Early regenerates in both muscle beds reacted with antibodies against the heavy chain of foetal, slow and superfast myosins, but not with antibodies against fast myosin. In the long-term, regenerates innervated by the EDL nerve expressed only superfast myosin whereas in the regenerates innervated by the soleus nerve most fibres expressed only slow myosin and only a few fibres reacted exclusively with the anti-superfast myosin antibody even after 210 days. In contrast, EDL and soleus muscles regenerating in their own beds expressed foetal, slow and fast myosin, but did not express superfast myosin. The isometric contraction times of the various types of regenerates reflected the types of myosin synthesized. It is concluded that jaw and limb muscle cells exist as two distinct allotypes, each having a distinct repertoire for the expression of adult isomyosins, and that within that repertoire isomyosin gene expression can be modulated by the nerve. Thus, myosin gene expression in skeletal muscle fibres is regulated by both myogenic and neurogenic mechanisms. PMID- 2899093 TI - Torsion of a teratoma in an undescended intra-abdominal testis: ultrasonographic findings. PMID- 2899094 TI - Secretion of dilevalol in breast milk. AB - The pharmacokinetics of unchanged and total (unchanged plus Glusulase [Biotechnology Systems, Boston, MA]) released dilevalol and secretion into human breast milk was studied in six healthy breast-feeding female volunteers administered a single 400-mg dilevalol hydrochloride capsule. In plasma, the mean Cmax for unchanged dilevalol, 485 ng/mL was reached at 0.8 hour (tmax) and the AUC(48 hours) was 1435 hr X ng/mL. Pharmacokinetic analysis of unchanged dilevalol in plasma showed that dilevalol was distributed and eliminated with half-lives of 0.9 and 8.2 hours, respectively. Breast milk concentrations of unchanged dilevalol as a function of time, paralleled those of plasma but were consistently lower. The milk Cmax, 149 ng/mL, occurred during the 0 to 2 hour collection interval; the AUC(42 hours) for unchanged dilevalol in milk was 663 hr X ng/mL. The mean milk to plasma concentration ratio was 0.46. The unchanged dilevalol plasma concentrations were 12 to 18% those of total drug suggesting that the drug is extensively conjugated. By contrast, the concentrations of unchanged dilevalol in breast milk, based on Cmax and AUC data were 63 to 94% those of total drug, indicating that very little conjugated drug is secreted into breast milk. Through 48 hours, a mean of only 27 micrograms dilevalol or 0.007% of the administered dose was secreted into breast milk, which is much less than that reported for other beta blockers. PMID- 2899092 TI - In vivo administration of lymphocyte-specific monoclonal antibodies in nonhuman primates. IV. Cytotoxic effect of an anti-T11-gelonin immunotoxin. AB - The cytotoxic effect of a lymphocyte-specific immunotoxin formed by disulfide conjugation of an anti-T11 monoclonal antibody with the ribosome-inactivating protein gelonin was assessed in vitro on peripheral blood T cells and in vivo on splenic and lymph node T cells of macaque monkeys. This immunotoxin was cytotoxic to proliferating peripheral blood T cells in vitro as measured by both direct and indirect assays. Two sequential intravenous infusions into macaque monkeys achieved plasma concentrations of immunotoxin far in excess of those shown to be cytotoxic for cultured T cells and coated all T cells in lymph nodes and spleen with intact immunotoxin for four days. However, the cytotoxic effect of the immunotoxin on T cells in vivo was considerably less than that predicted by the in vitro studies. Further experiments suggested that the state of activation of the targeted T cell population in vivo, or the appearance of anti-immunotoxin antibodies, which occurred in all infused monkeys, might attenuate immunotoxin mediated cell killing in vivo. These studies illustrate the significant differences between the action of immunotoxin conjugates in vitro, and those seen when these conjugates are utilized as therapeutic agents in vivo. PMID- 2899095 TI - Pharmacokinetics of cetamolol in hypertensive patients with normal and compromised renal function. AB - The efficacy, safety, and pharmacokinetic parameters of a 30-mg oral dose of cetamolol hydrochloride (Betacor), a new synthetic cardioselective beta adrenoceptor antagonist, with intrinsic sympathomimetic activity, were evaluated by studying 32 hypertensive patients with normal renal function or different degrees of renal impairment. After administration of cetamolol, serial blood and urine sample collections, as well as vital sign determinations for the next 48 hours, were performed in all patients (with the exception of urine collection, which was not possible in hemodialysis patients). Results indicate that cetamolol's pharmacokinetic parameters are significantly changed in patients who have moderate or severe renal impairment. Specifically, as the severity of renal impairment increased, the maximum serum concentration (Cmax) and the area under the serum concentration-time curve (AUC) increased, whereas the renal clearance (CLR), urinary excretion, and total body clearance (CL) decreased. Additionally, significant direct or inverse correlations for AUC, CL, CLR, and urinary excretion with creatinine clearance (CLCR) were demonstrated. In the subjects with mild renal impairment, the trends toward changes in the cetamolol pharmacokinetic parameters were evident, though small and not statistically significant. Although anuric, patients on hemodialysis still retained the ability metabolically to clear cetamolol at a rate of about one-third of that found in normal subjects. Reductions in blood pressure and heart rate also were found to be greater and more prolonged as the severity of renal impairment increased. There were no adverse drug or toxic effects noted in any of the study patients. Based on these findings, dosing recommendations are suggested for patients who have compromised renal function because of the effects of renal function on the pharmacokinetics of cetamolol. PMID- 2899096 TI - Effects of L-glutamine on tyrosinase and gamma-glutamyl transpeptidase of B-16 melanoma cells in culture. PMID- 2899097 TI - The distribution of 2,4-dinitrophenyl groups on Thy-1 positive cells in the epidermis of mouse following skin painting with 2,4-dinitrochlorobenzene. PMID- 2899098 TI - Is neurohormonal activation deleterious to the long-term outcome of patients with congestive heart failure? I. Introduction. PMID- 2899099 TI - Is neurohormonal activation deleterious to the long-term outcome of patients with congestive heart failure? II. Protagonist's viewpoint. PMID- 2899100 TI - Is neurohormonal activation deleterious to the long-term outcome of patients with congestive heart failure? III. Antagonist's viewpoint. PMID- 2899101 TI - Do positive inotropic agents adversely affect the survival of patients with chronic congestive heart failure? III. Antagonist's viewpoint. PMID- 2899102 TI - Inhibitory effect of oral cetirizine on in vivo antigen-induced histamine and PAF acether release and eosinophil recruitment in human skin. AB - The use of a noninvasive skin chamber technique in vivo in pollen-sensitive patients allowed us to quantify the time-course release of histamine and the recruitment of inflammatory cells (i.e., neutrophils, monocytes, and eosinophils) in skin sites challenged with pollen, histamine, and compound 48/80. The new H1 receptor antagonist, cetirizine 2 HCl, orally administered with 10 mg once a day to pollen-sensitive patients in a double-blind, crossover study versus placebo, induced a significant decrease in the wheal-and-flare cutaneous reaction induced by intradermal injection of pollen, histamine, and compound 48/80. It also significantly inhibited the immediate histamine release occurring in skin chambers after pollen introduction, whereas it did not significantly inhibit the late release. In patients receiving placebo, we detected platelet-activating factor-acether in media collected at the sixth hour from chambers filled with pollen. With cetirizine 2 HCl treatment, platelet-activating factor-acether was not detected in chamber media. Interestingly, cetirizine 2 HCl significantly reduced the eosinophil recruitment observed on the superficial dermis 24 hours after pollen challenge. PMID- 2899103 TI - Hypodense eosinophils in allergic rhinitis. AB - Based on density, function, and membrane receptors, peripheral blood eosinophils are a heterogeneous population of cells. Importantly, hypodense eosinophils (HE) are metabolically more active and likely to contribute to tissue injury. In the following study, peripheral blood from patients with allergic rhinitis (AR) was evaluated for the presence of HE. To accomplish this, blood was obtained from patients with ragweed AR, granulocytes were isolated and fractionated by continuous density Percoll gradients, and the density distribution of these cells was determined after centrifugation. A significantly higher percentage of peripheral blood eosinophils were hypodense (defined as density less than 1.081 gm/ml) in patients with AR when these patients were compared to control subjects, 30.0 +/- 5.0% versus 9.0 +/- 1.9%, p less than 0.01. Moreover, we also noted that an increased percentage of HE was found more often in patients with moderate-to severe AR than in subjects with none-to-mild disease (p less than 0.01). These data suggest that the appearance of HE in the circulation may relate to the development of allergic symptoms. Furthermore, our observations suggest that the HE, because of its enhanced metabolic activity and now its association with more symptomatic hay fever, may participate in the pathophysiology of AR. PMID- 2899104 TI - Enterobacter: an emerging nosocomial pathogen. PMID- 2899105 TI - Microbiological evaluation of a hospital delivered meals service using precooked chilled foods. AB - A delivered meals service supplying centrally produced, precooked, chilled foods to 24 hospitals was introduced in Plymouth Health District between August 1985 and July 1986. Over 18 months, 3393 food items were examined microbiologically, using the criteria recommended by the Department of Health and Social Security (DHSS) (1980). No Salmonella spp., Staphylococcus aureus or Clostridium perfringens were detected. Seventy-five (8.6%) of 876 cooked vegetable items had total viable counts (TVC) greater than 1 x 10(5) cfu g-1 (the recommended limit) after aerobic incubation at 37 degrees C for 48 h, whereas only 2.6% (66) of 2517 foods other than vegetables had TVC above this limit. Reasons for high counts were investigated and mostly corrected so that, whereas 8.4% of samples had TVC above recommended limits in the first 4 months of the study, only 1.6% exceeded this limit in the last 3 months. The value of microbiological standards for cook chill food and their use in hygiene control are assessed. PMID- 2899106 TI - Effect of chlorhexidine-containing detergent, non-medicated soap or isopropanol and the influence of neutralizer on bacterial pathogenicity. AB - In handwashing experiments with Salmonella typhimurium the effect of chlorhexidine (CHX) on the pathogenicity of surviving bacteria was assessed with and without a neutralizer in a mouse model of infection. Without neutralizer the LD50 of CHX handwash fluids was raised. Neutralizer in suspensions of untreated bacteria caused a reduction of LD50 up to 1.2 logs. Thus, in contrast to soap or alcohol, CHX without neutralizer exerted a slight 'depathogenizing' action and neutralizer a slight 'pathogenizing' effect in the experimental model used. However, in comparison to the efficiency of handwashing procedures which reduce the number of bacteria available for transfer by at least 3.0 to 4.2 logs, the size of these effects seems to be negligibly small and unpredictable. Therefore, the single most important parameter in assessing the potency of disinfectants remains the reduction of viable counts with time. PMID- 2899108 TI - Computer assisted analysis of wound infection in neurosurgery. AB - The effect of 10 variables on the development of postoperative infection in 536 clean elective neurosurgery patients was calculated using correlational, regression and discriminant analyses. The time of shaving the operation site, type of theatre ventilation and duration of operation were found to have a highly significant effect on the infection rate. The influence of season and age of patient was not evident on simple analysis, but both were found to be significant factors using regression analysis. The sex of patient, carriage of Staphylococcus aureus, airborne bacterial count, presence of bacteria in the wound and the use of prophylactic antibiotics did not have a significant effect on infection rates. PMID- 2899107 TI - Hand disinfection: a comparison of various agents in laboratory and ward studies. AB - The efficacy of 14 handwashing or disinfectant preparations was compared in laboratory tests on staff volunteers. The test organism, Escherichia coli, was applied to the fingertips and log reductions (LR) were measured following treatment with the test agent and control preparations (70% isopropanol and non medicated bar soap). Alcoholic preparations, particularly n-propanol and isopropanol were the most effective showing LRs of 3.1-3.8. Chlorhexidine (LR 2.9) and povidone-iodine detergent preparations were significantly more effective than non-medicated soap (LR 2.1), but triclosan products were not. In addition the residual effect of several of these formulations was assessed after 10 applications by comparing the survival of E. coli on the fingertips over a 32-min period. This number of handwashes compares favourably with those recorded during an 8 h nursing shift. Chlorhexidine-detergent consistently showed the best residual activity. Alcoholic formulations showed little or no residual effect. The survival studies show that on the whole gram-positive organisms (Staphylococcus aureus and Candida albicans) survive better on the skin than Gram negative bacilli (GNB). However, it would seem that GNB which are considered to be residents (Acinetobacter calcoaceticus and Enterobacter spp.) survive much better than many other GNB (Pseudomonas aeruginosa, E. coli and Proteus vulgaris). The Klebsiella species varied in survival times. Random sampling of ward staff hands showed that contamination with S. aureus and GNB was greater in dermatological and general wards than in an isolation unit, where handwashing or disinfection was carried out after every patient contact. No cross-infection occurred in the isolation ward during periods of study in which 70% alcohol, chlorhexidine-detergent and non-medicated soap were used. PMID- 2899109 TI - Bacteriuria during indwelling urethral catheterization. AB - The incidence of bacteriuria and the risk factors related to its acquisition were determined in a prospective study of 220 hospitalized patients. Bacteriuria was recorded in 97/220 (44%) of patients, in 42 cases within 48 h (Group A) and in 55 cases more than 48 h (Group B) after catheterization. The results of a multivariate analysis of Group A demonstrated that the reason for catheterization, the use of antimicrobial chemotherapy and the medical specialty of care were the only variables of those assessed associated with the acquisition of bacteriuria. In a similar analysis of Group B the number of days the catheter was in situ and the use of antimicrobial chemotherapy were the only factors which achieved statistical significance. PMID- 2899110 TI - 'Cialit' as a tissue preservative: a microbiological assessment. AB - We describe bacterial contamination of a 'Cialit'-preserved cartilage bank which continued after a variety of changes to the harvesting and preservation protocols during a 3-year prospective study. Our results emphasize the importance of adequate tissue bank microbiological screening. Alternative methods of tissue preservation should be considered. PMID- 2899111 TI - Assessment of the suitability of food colouring materials as indicators of bacterial contamination of enteral feeds. AB - The suitability of using food colouring materials in enteral feeds as indicators of bacterial contamination was examined. Experiments using Triosorbon, Clinifeed ISO or Vivonex Standard plus amaranth, carmoisine, ponceau 4R, sunset yellow FCF, tartrazine or erythrosine demonstrated that although the change in appearance of coloured feed could be linked with the presence of high numbers of bacteria in the feed, the converse was not always true. PMID- 2899112 TI - Evaluation of three disinfectants after in-use stress. AB - Solutions of 2.0% and 3.4% glutaraldehyde, and of 0.5% phenate with 0.18% glutaraldehyde were stressed with a microbial and organic soil load for the periods advocated by the respective manufacturers. The disinfecting efficacy of the stressed solutions was challenged with Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis, Mycobacterium bovis (BCG), a water Mycobacterium sp. and Candida albicans. The three disinfectants were active against the fast growing bacteria in appropriate dilutions; lesser dilutions of the glutaraldehyde solutions killed the mycobacteria and the yeast, while stressed phenate with glutaraldehyde did not. One hour exposure of the stressed disinfectants failed to kill the spore preparations while reducing the number of survivors. PMID- 2899114 TI - Eczema and skin lesions in health care staff. PMID- 2899113 TI - Survey of antibiotic prophylaxis in gastrointestinal surgery in Scotland--5 years on. AB - The results of a 5-year follow-up survey of the use of prophylactic antibiotics in gastrointestinal surgery in Scotland are reported. There have been significant increases in the routine use of prophylactic antibiotics during elective cholecystectomy (21% to 53% of surgeons; P less than 0.001) and appendicectomy (49% to 79% of surgeons; P less than 0.001). In addition a substantial number of surgeons used prophylactic antibiotics in selected high risk patients undergoing biliary tract surgery and gastroduodenal surgery. PMID- 2899115 TI - Vancomycin resistant lactobacilli. PMID- 2899117 TI - Ethylene oxide sterilization at 37 degrees C. PMID- 2899116 TI - Bacteraemia and coagulase-negative staphylococci. PMID- 2899118 TI - Air, antibiotics and sepsis in replacement joints. AB - Reducing bacterial contamination of the wound by limiting dispersal from the operating staff through the wearing of special occlusive clothing and by employing directional flow ventilating systems substantially reduces the risk of later joint sepsis. Inhibiting growth of those bacteria which reach the wound, by means of perioperative antibiotics, further reduces the incidence of joint sepsis. When all three means are used together the sepsis rate in the years after operation can be reduced to no more than a few per thousand. The hospital costs of any or all of these measures, in terms of the cases of sepsis avoided, are several times less than the costs of treating a septic joint. PMID- 2899119 TI - The role of clothing and drapes in the operating room. PMID- 2899120 TI - The role of antibiotics in preventing infections following total hip replacement. AB - The incidence of infection in hip replacement surgery from the MRC trial was less than 1% and it should be the aim of every centre to remain within this range. Some 50,000 total hip replacements are performed in the United Kingdom each year, and even this incidence would produce a significant number of revision arthroplasties. Perhaps the ideal combination of prophylaxis is to use an ultraclean air system together with short-course high-dose antibiotics delivered at the time of surgery. However, probably more important than anything else is the enforcement of a theatre discipline; large numbers of people should be prevented from moving around in the theatre and the theatre should remain a closed system allowing the clean air plenum ventilation to function. PMID- 2899121 TI - Surgical management of the infected arthroplasty. PMID- 2899122 TI - The choice between prophylactic agents for orthopaedic surgery. PMID- 2899124 TI - Restriction fragment mapping of Branhamella catarrhalis: a new tool for studying the epidemiology of this middle ear pathogen. PMID- 2899123 TI - [Long-term efficacy of anticholinergic and alpha-blockader drugs on the detrusor muscle in children with myelomeningocele]. AB - Pharmacological agents, essentially anticholinergic and alpha-blocking drugs, occupy an important place in the stabilization of congenital neurogenic bladders. In actual fact, the functional characteristics of the detrusor, contractility, compliance and functional capacity, are important factors in the prognosis of these neurogenic bladders, both for the future of the upper urinary tract and for the possibilities of continence. This behaviour of the detrusor may be pharmacologically modified not only by anticholinergic drugs, but also by alpha blockers due to the adrenergic innervation of foetal bladders by short neurones. This study compared the activity of these 2 drugs prescribed separately over a minimal period of 2 years to 54 children with congenital neurogenic bladder. The amplitude of vesical contraction was reduced in about 75% of cases with both drugs, but this result was obtained more rapidly with anticholinergic drugs than with alpha-blockers. No escape phenomenon over time was observed. Anticholinergic drugs were more effective on phasic contractions while alpha-blockers were more effective on rhythmic contractions. In contrast, they had an insignificant action on hypertonia. The increase in functional vesical capacity was 4 times greater with anticholinergic drugs than with alpha-blockers, possibly because of a simultaneous reduction in peripheral resistance with alpha-blockers. PMID- 2899125 TI - Characterization of enteroadherent-aggregative Escherichia coli, a putative agent of diarrheal disease. AB - Escherichia coli that exhibit the aggregative pattern of adherence to HEp-2 cells (enteroadherent-aggregative E. coli [EA-AggEC]) have been epidemiologically incriminated as a cause of diarrhea. We undertook a preliminary microbiological and pathogenetic characterization of 42 isolates of this putative pathogen. The strains were negative by tests with DNA probes for enteropathogenic, enterotoxigenic, enteroinvasive, and enterohemorrhagic E. coli and, by serotype, did not fit these categories. Thirty-nine of 42 strains had a 55-65-megadalton plasmid; many shared DNA homology. With one representative strain, plasmid transfer was accompanied by transfer of smooth lipopolysaccharide, fimbriae expression, and the aggregative property. EA-AggEC caused characteristic lesions in rabbit and rat ileal loops. The intestinal lesions and (Shiga-like) limb paralysis and death in rabbits inoculated with live organisms suggest toxin involvement; assays for Shiga-like toxins were negative. These preliminary results support the contention that EA-AggEC may represent a distinct category of diarrheagenic E. coli. PMID- 2899126 TI - [Metabolism of peptidoleukotrienes by leukocytes]. PMID- 2899127 TI - [Structure of biotin-binding site of biotin-dependent carboxylases]. PMID- 2899128 TI - Molecular cloning and complete nucleotide sequence of an adult T cell leukaemia virus/human T cell leukaemia virus type I (ATLV/HTLV-I) isolate of Caribbean origin: relationship to other members of the ATLV/HTLV-I subgroup. AB - We report the first complete nucleotide sequence of an adult T cell leukaemia virus/human T cell leukaemia virus type I (ATLV/HTLV-I) isolate from a British patient of Caribbean origin. Sequence comparisons of our proviral clone (HS-35) with other molecular clones are shown. We note the strong sequence conservation between isolates of Caribbean and Japanese origin (2.3% divergence), but demonstrate the higher homologies existing between isolates originating from similar geographical areas (approximately 1% divergence). Implications for the origin, evolution and dissemination of the ATLV/HTLV-I subgroup are discussed. Analysis of defective proviral clones isolated from the same genomic library is also reported, and suggests a pattern of proviral sequence deletions during the biogenesis of defective proviruses. PMID- 2899129 TI - Replication of the scrapie agent in hamsters infected intracerebrally confirms the pathogenesis of an amyloid-inducing virosis. AB - Following intracerebral infection of hamsters with scrapie agent replication started with or without a very short lag phase. Infectivity titres increased exponentially within 35 to 40 days post-infection to a maximum level of 3 x 10(9) LD50 per brain and then remained constant until death. Minimal detectable amounts of scrapie-associated fibrils (SAF) appeared at 42 days and reached high levels 56 days after inoculation. The first clinical symptoms were diagnosed at about 65 days and animals died after 85 to 95 days. These data confirm earlier results in which peripheral infection first revealed agent replication, then SAF formation and finally clinical disease. Unconventional virus diseases, therefore, can best be described as virus-induced, organ-specific amyloidoses. PMID- 2899130 TI - Enzymes of fatty acid beta-oxidation in developing brain. AB - Developmental profiles were determined for the activities of eight enzymes involved in fatty acid beta-oxidation in rat brain. The enzymes studied were the palmitoyl-CoA, octanoyl-CoA, butyryl-CoA, glutaryl-CoA, and 3-hydroxyacyl-CoA dehydrogenases, the enoyl-CoA hydratase (crotonase), and the C4- and C10 thiolases. With the exception of the thiolases, all of the activities (expressed on the basis of brain weight) increased during the postnatal period of brain maturation. The activity of octanoyl-CoA dehydrogenase was elevated markedly compared to that of palmitoyl-CoA dehydrogenase at all developmental stages and in all brain regions in the rat. A similar relationship between these enzymes was observed in various regions of adult human brain. Comparisons of the activities of the beta-oxidation enzymes in human brain versus human skeletal muscle and in cultured neural cell lines (neuroblastoma and glioma) versus cultured skin fibroblasts revealed that the elevated activity of octanoyl-CoA dehydrogenase relative to palmitoyl-CoA dehydrogenase was specific to the neural tissues. This relationship was particularly evident when the enzyme activities were normalized to the activity of crotonase. The data support previous findings with radiochemical tracers, indicating that the brain is capable of utilizing fatty acids as substrates for oxidative energy metabolism. The relatively high activity of the medium-chain fatty acyl-CoA dehydrogenase in neural tissue may represent an adaptive mechanism to protect the brain from the known encephalopathic effects of octanoate and other medium-chain fatty acids that readily cross the blood brain barrier. PMID- 2899131 TI - Chaotropic ions affect the conformation of quisqualate receptors in rat cortical membranes. AB - Binding of [3H](R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA) to quisqualate receptors in the presence of SCN- ions produced curvilinear Scatchard plots. Kinetic investigations of [3H]AMPA binding showed that the curvilinearity cannot be explained by assuming binding to two separate binding sites or by considering it due to cooperative interaction. A more likely explanation is that the quisqualate receptors exist in two states, one with high and one with low affinity for [3H]AMPA. Chaotropic ions change the relaxation constant between the two states. PMID- 2899133 TI - Properties of quisqualate-sensitive L-[3H]glutamate binding sites in rat brain as determined by quantitative autoradiography. AB - Quisqualate, a glutamate analogue, displaced L-[3H]glutamate binding in a biphasic manner, corresponding to "high-affinity" and "low-affinity" binding sites. High-affinity quisqualate sites were termed "quisqualate-sensitive L [3H]glutamate" binding sites. Quisqualate-sensitive L-[3H]glutamate binding was regionally distributed, with the highest levels present in the cerebellar molecular layer. This binding was stimulated by millimolar concentrations of chloride and calcium. The stimulatory effects of calcium required the presence of chloride ions, whereas chloride's stimulatory effects did not require calcium. All of the L-[3H]glutamate binding stimulated by chloride/calcium was quisqualate sensitive and only weakly displaced by N-methyl-D-aspartate, L-aspartate, or kainate. At high concentrations (1 mM), the anion blockers 4-acetamido-4' isothiocyanostilbene-2,2'-disulfonic acid and 4,4'-diisothiocyanatostilbene-2,2' disulfonic acid both reduced, by 41 and 43%, respectively, the stimulatory effects of chloride. At concentrations of 100 microM, kynurenate, L-aspartate, (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and L-2 amino-4-phosphonobutyric acid (L-APB) failed to displace quisqualate-sensitive L [3H]glutamate binding in the cerebellar molecular layer. In the presence of KSCN, however, 100 microM AMPA displaced 44% of binding. Quisqualate-sensitive L [3H]glutamate binding was not sensitive to freezing, and, in contrast to other chloride- and calcium-dependent L-[3H]glutamate binding sites that have been reported, quisqualate-sensitive binding observed by autoradiography was enhanced at 4 degrees C compared with 37 degrees C. Quisqualate-sensitive L-[3H]glutamate binding likely represents binding to the subclass of postsynaptic neuronal glutamate receptors known as quisqualate receptors, rather than binding to previously described APB receptors, chloride-driven sequestration into vesicles, or binding to astrocytic membrane binding sites. PMID- 2899132 TI - Differential control by N-methyl-D-aspartate and kainate of striatal dopamine release in vivo: a trans-striatal dialysis study. AB - Using the technique of trans-striatal dialysis in halothane-anesthetized rats, we have studied the effects of intrastriatally infused N-methyl-D-aspartate (NMDA), kainate, and quisqualate on the liberation of endogenous striatal dopamine. The striatal infusion of NMDA (10(-3)-10(-2) M) or kainate (10(-4)-10(-2) M) but not of quisqualate (up to 10(-2) M) for one 20-min fraction provoked a dramatic increase in striatal dopamine efflux up to a maximum of 1,200 and 3,400% of basal levels for NMDA and kainate, respectively. NMDA (10(-3) M) evoked liberation of striatal dopamine was totally blocked by coinfusion of 2-amino-5 phosphonovalerate (2-APV; 5 X 10(-4) M) and by the systemic injection of phencyclidine (3 mg/kg i.p.). The effects of NMDA (10(-3) M) were also totally antagonized in a dose-dependent manner by the striatal coinfusion of atropine (10(-7)-10(-4) M), and abolished in rats that had received bilateral striatal ibotenate lesions (10 micrograms/1 microliter) 1 week prior to implantation of the dialysis fiber. The striatal infusion of tetrodotoxin (10(-6) M) reduced basal dopamine efflux by 60-70% and abolished the NMDA (10(-3) M)-evoked liberation of striatal dopamine. The effects of kainate (10(-3) M) on striatal dopamine efflux were only partially reduced by doses of 2-APV or atropine that totally blocked the NMDA response, and were also partially resistant to tetrodotoxin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899134 TI - Cyclic AMP analogues potentiate kappa-opiate and attenuate alpha 2-adrenoceptor agonist effects on intrasynaptosomal free calcium. AB - The intrasynaptosomal free calcium concentration ([Ca2+]i) was measured in quin2 loaded synaptosomes prepared from rat cerebral cortex. Membrane-permeant cyclic adenosine-3',5'-monophosphate (cAMP) analogues [8-bromo-cyclic adenosine-3',5' monophosphate (8-Br-cAMP) and dibutyryl-cyclic adenosine-3',5'-monophosphate (db cAMP)] increased [Ca2+]i in a dose-dependent manner; The maximal increases were approximately 50% for 8-Br-cAMP and 35% for db-cAMP and occurred at approximately 10 microM with both analogues. Clonidine (1 microM) alone reduced [Ca2+]i by 26.5%; db-cAMP and 8-Br-cAMP attenuated this reduction to 14.2 and 8.2%, respectively. In contrast, the reduction (19.9%) in [Ca2+]i induced by the preferential kappa-opiate agonist dynorphin A(1-13) was not attenuated by the cAMP analogues; in fact, db-cAMP and 8-Br-cAMP potentiated the effect of dynorphin A(1-13) (1 microM), producing decreases in [Ca2+]i of 33.6 and 29.6%, respectively. We conclude that although alpha 2-adrenergic and kappa-opiate receptors both reduce [Ca2+]i, the alpha 2-adrenoceptor-mediated response and the kappa-opiate receptor-mediated response involve different effector mechanisms. It appears that presynaptic alpha 2-adrenoceptor agonist effects are linked to reductions in adenylate cyclase activity and cAMP production and a resultant increase in Ca2+ sequestration, Ca2+-channel blockade, or both. On the other hand, the kappa-opiate-mediated effects possibly involve an increase in cAMP production and a blockade of Ca2+ entry. PMID- 2899135 TI - Predicted amino acid sequence of bovine tyrosine hydroxylase and its similarity to tyrosine hydroxylases from other species. AB - The previously obtained cDNAs coding for bovine tyrosine hydroxylase (TH) mRNA (mRNATH) were further analyzed, and the entire nucleotide sequence was determined. The mRNATH consists of 1,706 nucleotides with an open reading frame for 491 amino acids, which corresponds to a calculated molecular weight of 55,011. The predicted amino acid sequence of bovine TH is compared with that of rat TH and shows a similarity of 66% in the amino terminal (amino acids 1-157) and 91% in the carboxy terminal (amino acids 158-491) region of the TH protein molecule. The carboxy terminal region has been shown to make up the catalytic site of TH and, therefore, is conserved to a greater extent in different species than the amino terminal region, which has been shown to be mainly responsible for the regulation of the catalytic activity of TH. Three of the four serine residues (Ser 8, 19, and 40) that have been shown to be substrates for various protein kinases in rat TH are also present in bovine TH and are located near the amino terminal end of the molecule. The amino acids from position 60 to position 66 of rat TH are not present in bovine TH, resulting in the absence of a predicted hydrophobic region as compared with rat TH. This difference could result in an altered degree of regulation by posttranslational phosphorylation and also association to cell organelle membranes of bovine TH as compared with rat TH. PMID- 2899137 TI - Multiple human tyrosine hydroxylase enzymes, generated through alternative splicing, have different specific activities in Xenopus oocytes. AB - A single human tyrosine hydroxylase (HTH) gene has been shown previously to generate four species of mRNA by alternative splicing. The four different HTH mRNAs were independently synthesized in vitro, using the SP6 transcription system. Each of these mRNA species was able to direct the synthesis of an active form of TH following injection into Xenopus oocytes. Quantitation of synthesized HTH polypeptides allowed the determination of the relative specific activity of each individual HTH form. A significant difference in specific activity was found between each form, suggesting that alternative splicing may play a role in regulating HTH activity in vivo. PMID- 2899136 TI - alpha-[3H]Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid binding to rat striatal membranes: effects of selective brain lesions. AB - The binding of alpha-[3H]amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA), a structural Glu analog, to rat striatal membranes was studied. In the absence of potassium thiocyanate and Cl-/Ca2+, saturation-curve analysis of [3H]AMPA binding suggested that a single class of noninteracting binding sites with a KD value of 340 +/- 27 nM was involved, although AMPA inhibition of [3H]AMPA binding set at a concentration of 100 nM suggested, in contrast, the presence of multiple populations of striatal binding sites. Several other excitatory amino acid receptor agonists and antagonists were tested, and the most potent and selective quisqualic acid (QA) receptor agonists (QA, L-Glu, and AMPA) were found to represent the most potent inhibitors of [3H]AMPA binding. N-Methyl D-aspartate receptor agonists and antagonists were ineffective as displacers of the [3H]AMPA binding. Lesions of intrastriatal neurons (using kainic acid local injections) and of corticostriatal afferent fibers led 2-3 weeks later to large decreases (63 and 30%, respectively) in striatal [3H]AMPA binding, whereas selective lesion of the nigrostriatal dopaminergic pathway (using nigral injection of 6-hydroxy-dopamine) was without any influence. Taken together, these results suggest that [3H]AMPA binding is primarily associated with postsynaptic intrastriatal neurons. Some [3H]AMPA binding sites may also be located presynaptically on corticostriatal nerve endings. So, in addition to the possibility that [3H]AMPA binding sites may be involved in corticostriatal synaptic transmission, it is interesting that these putative QA-preferring excitatory amino acid receptor sites may also play some role in autoregulatory processes underlying this excitatory synaptic transmission. PMID- 2899138 TI - Interleukin 2 promotes conjugate formation by purified LAK precursors and T lymphocytes: evaluation of conjugates using flow cytometric techniques. AB - The capacity of null cells, enriched in natural killer cells and lymphokine activated killer (LAK) cell precursors, and T cells to conjugate with tumor targets was analyzed using a flow cytometric assay. Both purified null and T lymphocytes had a similar capacity to conjugate with uncultured and cultured tumor targets prior to interleukin-2 (IL-2) stimulation. In addition, the frequency of conjugation did not correlate with the cytotoxicity expressed by these purified lymphocyte subpopulations, as null but not T cells were highly lytic for the K562 target. Following incubation in IL-2, however, the level of conjugation with tumor targets of both null and T lymphocytes was increased. Both effector populations formed stable conjugates within 6 min at 37 degrees C. The promotion of conjugation was associated with the induction of LAK activity by null but not T lymphocytes. No differences were apparent between the capacity of either IL-2-activated null or IL-2-activated T lymphocytes to conjugate with tumor targets, although only the former efficiently lysed them. Conjugation of both null and T effectors with tumor targets required the presence of Mg2+ cations because it was inhibited by the presence of EDTA (38-72% inhibition) but not EGTA. Conjugation was also inhibited by an antibody (MHM 23) recognizing the beta-chain shared by LFA-1, MAC-1, and P150/95 molecules. These observations demonstrate that both null and T lymphocytes responded to IL-2 with an increase in their ability to conjugate with tumor targets. The frequent formation of stable conjugates under these conditions by cells with both cytolytic and noncytolytic capacity failed to define conjugation as the only major condition proximate to LAK lysis. PMID- 2899139 TI - Diagnostic factors in intermediate and high-grade lymphomas: pathologic, immunologic, and clinical. PMID- 2899140 TI - Major prognostic factors of adult patients with advanced T-cell lymphoma/leukemia. AB - Eighty-one adult patients with advanced T-cell lymphoma/leukemia including 54 with adult T-cell leukemia/lymphoma (ATL), who were treated between 1981 and 1983 with vincristine, cyclophosphamide, prednisolone, and doxorubicin (VEPA) or VEPA plus methotrexate (VEPA-M) in randomized fashion, were evaluated for pretreatment characteristics. The overall complete response (CR) and the 4-year survival rates were 39.5% and 19.4%, respectively, and 69% of 32 CR patients had relapses, indicating the need for development of new effective regimens for the disease. In a multiple logistic regression analysis, only three factors, leukemic manifestation, poor performance status (PS), and a high lactate dehydrogenase (LDH) level, were significantly associated with the poor response rate. In a Cox proportional hazards model analysis, shortened survival was again significantly associated with poor PS and a high LDH level, but not with a clinical diagnosis of ATL. The two factors, PS and LDH level, that were found to be significantly associated with both CR and survival rates, were used to construct a model containing six categories of patients at increasing risk for poor response and shortened survival. These categories divided the patients into three groups with respective CR and 4-year survival rates of 75% and 53% for low-risk, 45% and 15% for moderate-risk, and 15% and 0% for high-risk. The results indicate that PS and LDH levels were the most important in predicting the response and survival of an adult patient with advanced T-cell lymphoma/leukemia. The prognosis of patients with usual peripheral T-cell lymphoma, excluding ATL, was comparable with that of advanced B-cell lymphoma. These results have important implications for the design of new prospective therapeutic trials. PMID- 2899141 TI - Potential for dietary amino acid precursors of neurotransmitters to overcome neurochemical changes in acute T-2 toxicosis in rats. AB - Experiments were conducted to determine the potential for overcoming T-2 toxin induced changes in brain neurotransmitter concentrations through dietary manipulation. Rats were fed either a tryptophan-deficient, gelatin-based diet or the same diet supplemented with a mixture of large neutral amino acids for 4 d. Rats were then dosed with 0 or 2.0 mg T-2 toxin/kg body weight and killed 4, 8 or 12 h after dosing. The large neutral amino acid supplements successfully reduced brain concentrations of tryptophan and serotonin in control rats, but this was not enough to overcome the acute effects seen in T-2 toxin-treated rats. A further experiment was then conducted to monitor the effect of T-2 toxin on the ratio of free to protein-bound tryptophan in plasma. Total plasma tryptophan increased in T-2 toxin-treated rats, although there were no significant differences in the ratio of free to protein-bound tryptophan. A final experiment was conducted to determine the specificity of the T-2 toxin effect on concentrations of plasma amino acids. Concentrations of amino acids that use the large neutral amino acid transport system into the brain were higher in T-2 toxin treated animals. The only other amino acid that had a higher concentration was arginine. It was concluded that acute doses of T-2 toxin may selectively alter membrane transport of amino acids. PMID- 2899142 TI - The dissolution rate and bioavailability of hydrochlorothiazide in pellet formulations. AB - The influence of non-active ingredients in the manufacture of pellets on in-vitro dissolution rate and on bioavailability of hydrochlorothiazide has been studied. Pellets were formulated using either microcrystalline cellulose or microcrystalline cellulose-carboxymethylcellulose sodium blends as matrix, and hydrochlorothiazide as the active ingredient. In-vitro drug release from the different pellet formulations was retarded in comparison to a conventional tablet formulation and was dependent on the nature of the non-active ingredient and, for the microcrystalline cellulose-carboxymethylcellulose sodium blend, of the dissolution medium. In-vivo bioavailability of both pellet formulations was low compared with that of the conventional tablet and the plasma concentration-time profiles did not suggest slow release. PMID- 2899143 TI - Vesicular systems (niosomes and liposomes) for delivery of sodium stibogluconate in experimental murine visceral leishmaniasis. AB - Suppression of Leishmania donovani liver amastigotes by sodium stibogluconate has been determined in a murine model of experimental visceral leishmaniasis. Niosomal and liposomal drug formulations were equiactive and both increased drug efficacy by an order of magnitude compared with that of free drug. Niosomes containing 30 mol % cholesterol were prepared from three different non-ionic surfactants and no significant difference in activity was detected among the different drug-loaded niosomes. Both negatively charged and neutral vesicles were found to be equally effective. However, vesicle cholesterol content had a slight influence on the antiparasitic activity of the drug-loaded niosomes. Empty vesicles produced a dose-dependent parasite suppression for all vesicles studied. Studies of antimony distribution in the mouse using neutron activation analysis showed high liver levels after i.v. administration of the carrier forms of the drug. PMID- 2899144 TI - Evaluation of reconstituted Sendai virus envelopes as intra-articular drug vectors: effects on normal and experimentally arthritic rabbit knee joints. AB - Fusogenic vesicles reconstituted from the envelopes of Sendai virus particles were injected into rabbit knee joints (both normal and experimentally arthritic) to evaluate the in-vivo biocompatibility of these putative drug carriers. The reconstituted Sendai virus envelopes (RSVE) were greater than 80% retained within the arthritic knee joints after 24 h and studies with 125I- and fluorescein labelled RSVE both showed association of the vesicles with the synovia of arthritic and healthy joints. However, RSVE were found to cause inflammation after intra-articular injection, as judged by joint swelling and histological assessment, and these effects were exacerbated by successive administrations. RSVE-entrapped methotrexate, whether free or conjugated to human serum albumin, was ineffective in preventing the irritancy of RSVE or in reducing the chronic inflammation in joints affected by an experimentally induced arthritis. PMID- 2899145 TI - Association of liposome-entrapped [3H]methotrexate with thioglycollate-elicited macrophages in-vitro. AB - The association of free or liposome-entrapped [3H]methotrexate [( 3H]MTX) with thioglycollate-elicited macrophages was investigated in-vitro. [14C]Cholesteryl oleate was incorporated into the liposomes as a lipid marker. [3H]MTX association with the macrophages was 5 to 9-fold higher with liposome-entrapped [3H]MTX than with the free drug. Macrophage-liposome association was biphasic, temperature dependent and saturable at high liposomal lipid concentration. A high liposome cholesterol (CH) content or the presence of 2,4-dinitrophenol or colchicine also reduced macrophage-liposome association. PMID- 2899146 TI - Transport characteristics of propantheline across rat intestinal brush border membrane. AB - The transport mechanism of propantheline, an anti-acetylcholine quaternary ammonium compound, has been studied using brush border membrane vesicles isolated from rat small intestine. The uptake of propantheline was facilitated by the transmembrane electrical potential difference (cell interior negative) induced by NaSCN, NaI or valinomycin. But this effect was a secondary action; in the initial phase of propantheline uptake (less than 5 min), there was no facilitating effect. When the transmembrane potential difference was induced after propantheline uptake had reached a steady state, there was an overshoot of the drug. Therefore, it is suggested that the transport of propantheline across the brush border membrane consists of at least two processes. In the first, propantheline rapidly binds to the brush border membrane, in the second it enters into epithelium driven by the negative transmembrane electrical potential difference. Cationic tertiary amines such as chlorpromazine, imipramine and promethazine markedly inhibited propantheline uptake. These results suggest that there is a common absorption process for tertiary amines and quaternary ammonium compounds. PMID- 2899147 TI - Depolarizing effect of various local anaesthetics on the Helix aspersa neurons: dose-response relationship. AB - The depolarizing effect of various local anaesthetics (LA) on the membrane potential of Helix central neurons has been examined. There is a relation between depolarizing effect and concentration of LA in the bath that is linear over a range of concentrations. The slope of the curve is significantly higher for amethocaine (tetracaine) than for procaine while for dibucaine the dose-response relation is not linear. The blockade of a response to acetylcholine (ACh) is about two fold higher for dibucaine and amethocaine than for procaine. These results suggest that both amethocaine and procaine act at the ACh-site in addition to their binding with specific sites located within the ionic channel lumen; dibucaine appears to act through another mechanism. PMID- 2899148 TI - Evaluation of different drugs in two models of immediate hypersensitivity. AB - The effect of the calcium antagonists, verapamil, nicardipine and diltiazem, the two cromones, disodium cromoglycate and SM-857 (11-oxo-11H-pyrido[2,1 b]quinazoline-2-carboxylic acid), and the anthelmintic, diethylcarbamazine citrate, have been compared on the ovalbumin (OA)-induced contraction of the isolated trachea and longitudinal muscle-myenteric plexus (LM-MP) from sensitized guinea-pigs. The calcium antagonists prevented the OA-induced contractions in LM MP and to a lesser degree the OA-induced contractions in trachea. Similar doses of SM-857 protected both tissues but neither cromoglycate (10(-5)M) nor diethylcarbamazine (10(-5)M) affected these contractions. The OA-induced contraction in trachea had a tonic phase that was not present in the LM-MP response. Only the calcium antagonists succeeded in relaxing this OA tonic component, diltiazem being the more potent. These results unmask different mechanisms of drug action on immediate hypersensitivity and specific sensibilities, depending on the kind of tissue. PMID- 2899149 TI - Paroxetine, a selective 5-hydroxytryptamine uptake inhibitor with antidepressant properties, lacks amphetamine-like stimulus properties in an operant drug discrimination bioassay in rodents. AB - To evaluate whether the novel antidepressant paroxetine has any possible amphetamine-like actions, rats were trained to discriminate (+)-amphetamine sulphate in a standard two lever operant drug discrimination (DD) procedure using a fixed ratio 10 schedule of food reinforcement with a quantal, lever selection, index of the amphetamine stimulus. The 'training' dose of amphetamine was 1 mg kg 1, i.p. Rats trained with this dose of amphetamine (n = 15) learned the drug discrimination rapidly over 30 training sessions and discriminative performance in these animals was subsequently maintained at a high level of accuracy (90% correct) over a prolonged time. In tests in these trained animals, amphetamine itself and the antidepressant agents nomifensine and tranylcypromine all produced clear, unequivocal dose-related generalization to amphetamine with ED50s of 0.2, 0.5 and 1.6 mg kg-1 respectively (as determined by probit analyses). In tests with paroxetine hydrochloride it was established that, over the dose range 0.3 to 10 mg kg-1, no evidence was seen of generalization to the amphetamine stimulus. These data confirm earlier studies which suggested that some antidepressants may possess abuse potential because of their ability to induce amphetamine-like internal states. In contrast, paroxetine is devoid of such properties. PMID- 2899150 TI - The anxiolytic and anxiogenic actions of ethanol in a mouse model. AB - The administration to mice of ethanol in the drinking water for 7 days modified exploratory activity (rearings/line crossings) in an anxiety testing box separated into white and black sections with an interconnecting door. During ethanol intake mice exhibited reduced anxiety responding, shown as increased rearings and line crossings in the white section, to which the mice are normally averse, with corresponding decreased behaviour in the black section. When naive mice were presented with a choice between normal drinking water and drinking water containing ethanol, they consumed sufficient of the latter to secure a full anxiolytic response, making up the total volume of fluid required by also drinking the former. A 48 h withdrawal from a 14 day treatment with ethanol caused a reversed profile of exploratory behaviour, directed preferentially at the black section of the test box, and indicative of an anxiogenic response. Diazepam, tiapride or clonidine given twice daily during withdrawal from ethanol could each secure a reduction in the withdrawal anxiogenesis. It is concluded that the simple model of anxiety described in the mouse may be useful for eludicating the mechanisms involved in the anxiolytic and anxiogenic potential of ethanol and may aid the search for novel agents having potential to suppress withdrawal anxiogenesis. PMID- 2899152 TI - Gastric emptying of large single unit dosage forms. AB - The gastrointestinal transit of two single unit dosage forms has been followed in healthy subjects under different feeding conditions. Transit was affected by the size of the meal administered. When two tablets were given concurrently they often emptied from the stomach at or about the same time, but in a number of cases the two units were seen to empty at widely different times. PMID- 2899151 TI - Interfacial tensions and partition coefficients in water/heptane systems containing 2,6-diisopropylphenol, n-alkylphenols and cycloalkanols. AB - The free energies of absorption, dehydration, and transfer in a heptane-water system for a set of phenolic compounds and a series of cycloalkanols have been investigated. The free energy of adsorption depends only upon the molecular surface area of the hydrophobic fraction of the molecule, whereas the free energy of dehydration is independent of this fraction. PMID- 2899153 TI - Contractile activity of calcitonin gene-related peptide on pulmonary tissues. AB - Rat calcitonin gene-related peptide was shown to be a very potent contractile agent on guinea-pig trachea, contractions being observed at 10 pM and maximal contractions (32-36% of the methacholine maximum) being observed between 0.3 and 13.3 nM. The response was largely inhibited (88%) by pretreatment with indomethacin indicating that the effect was mediated through the secondary generation of cyclooxygenase products. PMID- 2899154 TI - Kinetic mechanism for the intestinal absorption of ofloxacin. AB - The absorptive behaviour of ofloxacin, a quinolone antibacterial agent, was studied following recirculation in small intestine of both male and female rats, at initial doses ranging from 0.125 to 5 mg mL-1. A saturable Michaelis-Menten process is suggested to explain the intestinal absorption. No significant differences were found in the absorption parameters per metabolic weight unit. PMID- 2899155 TI - In-vivo studies with the opioid antagonist, 16-methylcyprenorphine. AB - The effect of the opioid antagonist, 16-methylcyprenorphine (RX8008M), on the antinociceptive action of the mu-selective agonist, morphine, and the kappa selective agonist, U50488H, has been investigated in the mouse abdominal constriction test. RX8008M produced a dose-dependent antagonism of the antinociceptive effect of morphine, but did not antagonize the response to U50488H. RX8008M should prove a useful probe for the in-vivo characterization of the receptor selectivity of opioid drugs. PMID- 2899156 TI - A modified transmembrane migration method for evaluating the spermicidal potency of some nonoxynol compounds. AB - The transmembrane migration technique, a simple method in-vitro for quantitatively assessing the effects of a drug on human sperm motility, has been evaluated. The original method has been modified to include a preincubation step, and the incubation time has been reduced to 90 min. In semen samples possessing sperm concentrations of less than 75 x 12(6) spermatozoa mL-1 the volume of the lower reservoir has been reduced to 1 mL. This modified method has been used to compare the spermicidal potency of the widely employed non-ionic surfactant nonoxynol-9, with nonoxynol-5 and nonoxynol-15 (containing, respectively, fewer and more ethylene oxide units per molecule). The rank order of spermicidal potency of the compounds evaluated was nonoxynol-9 = nonoxynol-5 greater than nonoxynol-15. PMID- 2899157 TI - A method for stabilization of monoamine oxidases in homogenates of rat intestine epithelium. AB - In a homogenate of epithelium isolated from the small intestine of male Wistar rats, the amine oxidase activity with 10(-3)M tyramine was 9200 +/- 200 nmol (g tissue)-1 h-1 of which 91% was due to the A form of monoamine oxidase (MAO) and 9% to the B form. Semicarbazide-sensitive amine oxidase activity was not detected with either 10(-3)M tyramine or 10(-4)M benzylamine as substrate. However, it was detectable in the homogenate of the gut residue where the activity with 10(-4)M benzylamine was 3600 +/- 200 nmol (g tissue)-1 h-1. The MAO activity, in homogenates of epithelium prepared with 0.1 M sodium phosphate pH 7.4, was stable at 4 degrees C for at least 6 h whilst at minus 20 degrees C it decreased by 70% within 24 h. Incorporation of 10% (v/v) glycerol into the homogenization medium stabilized the enzymes. The total activity and proportions due to MAO-A and MAO-B and kinetic constants for tyramine and 5-hydroxytryptamine, did not alter during 5 weeks storage at -20 degrees C. The ability to store tissue homogenates should facilitate studies of intestinal amine oxidases. PMID- 2899158 TI - Beta-adrenoceptor stimulating effects of phenylephrine and noradrenaline in the rat pulmonary vascular bed. AB - The effects of phenylephrine and noradrenaline have been investigated on the perfusion pressure of the rat isolated lung. Both drugs (0.3-30 micrograms) produced a dose-dependent decrease in perfusion pressure elevated by 20 mM KCl, which was reversed to a dose-dependent increase after addition of propranolol (1 x 10(-7) M) to the perfusion fluid. Increments due to both agonists in the presence of propranolol were antagonized by prazosin (1 x 10(-6) M). Propranolol, but not prazosin, elevated the basal perfusion pressure. The results indicate that phenylephrine and noradrenaline are more effective in stimulating beta adrenoceptors than alpha-adrenoceptors in the rat pulmonary vascular bed and that beta-adrenoceptors may regulate the vascular tone of the rat pulmonary circulation. PMID- 2899159 TI - Dopamine-mediated behaviours produced in naive mice by bromocriptine plus SKF 38393. AB - The ability of bromocriptine and SKF38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1 phenyl-1H-3-benzazepine) to produce some dopamine-mediated behaviours has been assessed in mice. Soon after injection, SKF38393 produced moderate increases in grooming and sniffing which were not very intense, while bromocriptine (with or without SKF38393) inhibited all grooming behaviour. Bromocriptine alone also depressed rearing and sniffing in the first hour and SKF38393 alone was without effect on rearing, but the combination produced a marked increase in the incidence of both rearing and sniffing, both of which behaviours appeared to be stereotyped. When bromocriptine-induced locomotor stimulation was peaking about 3 h after injection, as measured in automated activity cages in previous studies, there was an increase in sniffing and rearing, the incidence of which was unaffected by the addition of SKF38393, perhaps due to the shorter duration of action of SKF38393 than of bromocriptine. The data indicate that the D-1 agonist SKF38393 can qualitatively and quantitatively alter the behavioural spectrum produced by the D-2 agonist bromocriptine. PMID- 2899160 TI - High doses of L-naloxone but neither D-naloxone nor beta-funaltrexamine prevent hyperthermia-induced seizures in rat pups. AB - The effects of the non-specific opiate antagonist L-naloxone and the inactive isomer D-naloxone, as well as the specific mu receptor antagonist beta funaltrexamine, have been examined on hyperthermia-induced seizures in unrestrained 15 days old rats. Saline-injected animals exposed to an ambient temperature of 40 degrees C showed a gradual increase in body temperature reaching a maximum of 42 +/- 0.1 degrees C at 50 min exposure. At this time all the pups had seizures and died. Similar results were obtained when the animals were pretreated with different doses of D-naloxone and beta-funaltrexamine. Rats pretreated with L-naloxone also showed an increase in rectal temperature; but the temperature was lower than in saline-injected animals. Only high doses of L naloxone prevented seizures and deaths. These data indicate that endogenous opioid peptides may play a role in seizures induced by hyperthermia and that receptors other than mu receptors could be involved in hyperthermia-induced seizures. PMID- 2899161 TI - The effect of repeated oral doses of azelastine hydrochloride on antipyrine half life in normal volunteers. AB - Treatment with azelastine 4.4 mg twice daily for 21 days did not produce any change in salivary antipyrine elimination in 8 normal volunteers. PMID- 2899162 TI - Proteoglycan biosynthesis as a determinant of patella damage in the murine antigen-induced arthritis model. AB - The incorporation of 35SO4 into cartilage proteoglycan has been employed as a measure of patella damage in the murine antigen-induced arthritis model. In a preliminary set of experiments, where both the proteoglycan concentration and 35SO4 incorporation were determined in control and arthritic patella over a 2 day to 6 day week period, the arthritic joint contained significantly higher levels of radioactivity compared with the controls. A subsequent study over an extended period of 10 weeks confirmed the earlier results, and indicated that the 6 week samples showed the greatest difference (71%) in 35SO4 incorporation between the arthritic and control patella. PMID- 2899163 TI - The serum amyloid P response in the mouse air pouch. AB - Levels of the acute phase reactant serum amyloid P (SAP) have been measured in the mouse pouch model of rheumatoid arthritis. Implantation of cartilage resulted in a significant and rapid elevation in the SAP concentration, which remained high for the duration of the experiment (14 days). Initial studies with several clinically employed antirheumatic drugs indicated that dexamethasone and cyclosporin A had a marked inhibitory effect. PMID- 2899164 TI - Alpha adrenoceptor-mediated vasoconstriction in rat hindlimb: innervated alpha-2 adrenoceptors in the saphenous arterial bed. AB - The alpha adrenoceptor subtypes mediating vasoconstriction to exogenous agonists and to spinal sympathetic nerve stimulation have been characterized in the autoperfused (constant flow) femoral (predominantly skeletal musculature) and saphenous (predominantly cutaneous) vascular beds of the pithed rat. Intra arterial infusion of the alpha-1 adrenoceptor agonist, methoxamine, increased perfusion pressure in both vascular beds over the same range of infusion rates, and the maximum responses were similar. The selective alpha-2 adrenoceptor agonist, B-HT 933, also increased perfusion pressure in both beds, although the maximum response to B-HT 933 in the saphenous bed was approximately twice that observed in the femoral bed. Responses to methoxamine were blocked by the alpha-1 adrenoceptor antagonist, prazosin (0.1 mg/kg), but not the alpha-2 adrenoceptor antagonist, rauwolscine (1 mg/kg), or by the selective postjunctional alpha-2 adrenoceptor antagonist, SK&F 104078 (1 mg/kg). Conversely, responses to B-HT 933 were blocked by rauwolscine and by SK&F 104078, but not by prazosin. Vasopressor responses to B-HT 933 in both vascular beds of the rat hindlimb also were reduced markedly by the calcium channel blocker, nifedipine (1 mg/kg), whereas responses to methoxamine were relatively resistant to inhibition by nifedipine. In the femoral bed, as in the systemic arterial circulation, responses to sympathetic nerve stimulation were strongly inhibited by prazosin, were potentiated by rauwolscine and were unaffected by SK&F 104078. In contrast, in the saphenous arterial bed, the responses to sympathetic nerve stimulation were inhibited by all three antagonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899165 TI - Tertatolol ameliorates renal function in rats with chronic renal failure. AB - Tertatolol is a new beta-blocking agent which induces renal vasodilation in experimental animals and humans and increases glomerular filtration rate (GFR), diuresis and natriuresis. The mechanisms underlying renal effects of tertatolol are not known. Our aims were to establish whether tertatolol influences renal function by a systemic or by an intrarenal effect and to assess whether tertatolol could maintain GFR in chronic renal failure. Tertatolol but not propranolol when given as i.v. bolus injection at the dose of 25 and 50 micrograms/kg. b.w. induces a significant increase in GFR and perfusate flow rate (PFR) in an isolated perfused kidney model [GFR: tertatolol, 25 micrograms/kg; preinjection: 0.477 +/- 0.077 ml/min/g of kidney; 30 min postinjection: 0.996 +/- 0.114 ml/min/g of kidney. Tertatolol (50 micrograms/kg) preinjection: 0.517 +/- 0.040 ml/min/g of kidney; 30 min postinjection: 0.879 +/- 0.035 ml/min/g of kidney. Propranolol (500 micrograms/kg) preinjection: 0.574 +/- 0.045 ml/min/g of kidney; 30 min postinjection: 0.538 +/- 0.029 ml/min/g of kidney. PFR: tertatolol, 25 micrograms/kg, preinjection: 30.00 +/- 0.79 ml/min; 30 min postinjection: 36.20 +/- 2.58 ml/min. Tertatolol (50 micrograms/kg) preinjection: 29.30 +/- 1.44 ml/min; 30 min postinjection: 38.01 +/- 1.87 ml/min. Propranolol (500 micrograms/kg) preinjection: 28.70 +/- 1.04 ml/min; 30 min postinjection: 28.30 +/- 0.91 ml/min]. In the same preparation tertatolol significantly increases urine flow rate and Na+ excretion [urine flow rate: tertatolol (25 micrograms/kg) preinjection: 28.28 +/- 4.10 microliter/min; 60 min postinjection: 38.23 +/- 6.74 microliter/min. Tertatolol (50 micrograms/kg) preinjection: 24.02 +/- 0.63 microliter/min; 60 min postinjection: 33.18 +/- 2.07 microliter/min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899166 TI - Pronounced supersensitivity of postjunctional alpha adrenoceptors after denervation of fish melanophores. AB - The aggregation of melanosomes within melanophores (pigment cells) attached to isolated scales from the cuckoo wrasse (Labrus ossifagus L.) can be elicited either by stimulation of intrinsic nerves (electrical field stimulation of K+ depolarization) or by adrenoceptor agonists. The melanophores of isolated scales survived in a culture medium for up to 20 days. During this period a progressive increase in sensitivity to exogenously applied noradrenaline took place. After 8 days of isolation there was an about 300-fold increase in sensitivity to noradrenaline. The increased sensitivity was accompanied by a progressive loss of the nerve-elicited response during the first days of isolation. Before and during this early period cocaine was found to potentiate the effect of noradrenaline about 8-fold. On the 3rd day after isolation the effect of cocaine was lost, which coincided fairly well with the time when the nerve-mediated response was lost. The early developing increase in sensitivity to noradrenaline (8-fold) is therefore most likely caused by loss of presynaptic amine uptake, but the main part (50-fold) of the increase in sensitivity presumably has other explanations, like changes in the receptor population. PMID- 2899167 TI - Altered pharmacokinetic-pharmacodynamic relationship of heptabarbital in experimental renal failure in rats. AB - The purpose of this investigation was to determine whether renal dysfunction is associated with an alteration in the concentration-anesthetic effect relationship of heptabarbital (HB). Adult female rats were pretreated with uranyl nitrate (5 mg/kg i.v.) to produce renal dysfunction. Saline-injected rats served as controls. The concentration-effect relationship of HB was determined both at onset of loss of righting reflex (LRR) during an i.v. infusion (0.563 mg/min) and at offset of LRR after administration of a bolus dose (82 and 111 mg/kg in renal failure and controls, respectively, inducing similar durations of effect). In renal failure HB concentrations in serum (total and free) and in brain and cerebrospinal fluid (CSF) both at onset and offset of LRR were reduced significantly. When HB was infused at different rates (0.225, 0.563 and 1.50 mg/min) rats with renal impairment had slightly increasing HB concentrations at onset of LRR with increasing infusion rate, not only in serum and brain but also in CSF. When HB was administered in different bolus doses (71, 77, 80 and 96 mg/kg i.v.) the duration of effect increased linearly with the logarithm of the dose, but HB concentrations in serum (both total and free), brain and CSF at offset of LRR were similar, indicating the absence of (inter)active metabolites. The results indicate that renal dysfunction is associated with an increased sensitivity of the brain to HB, which is unrelated to changes in the disposition of HB. PMID- 2899168 TI - Psychopharmacological consequences of activation of beta adrenergic receptors by SOM-1122. AB - SOM-1122 was found to be a high-affinity, partial agonist for beta adrenergic receptors. SOM-1122 inhibited the binding of [125I]iodopindolol to membranes prepared from rat cerebral cortex and cerebellum. GTP regulated the binding of SOM-1122 by increasing the Hill coefficient in both tissues and reducing the affinity of the receptor for SOM-1122 in the cerebellum. SOM-1122 increased the concentration of cyclic AMP in slices of rat cerebral cortex in a dose-dependent manner; this effect was antagonized by propranolol. Two lines of evidence suggested that SOM-1122 was centrally active after peripheral administration. First, SOM-1122 inhibited the binding of [125I]iodopindolol in vivo in a dose dependent manner. Second, after chronic infusion with SOM-1122 for 7 days, the density of beta adrenergic receptors in the cerebellum was reduced; receptor density also was reduced 18 hr after acute administration of SOM-1122, although to a lesser extent. SOM-1122 was found to be behaviorally active. It reduced locomotor activity and reduced response rate under a multiple fixed-interval, fixed-ratio schedule in a dose-dependent manner. SOM-1122 also reduced response rate and increased reinforcement rate under a differential-reinforcement-of-low rate schedule. These behavioral actions of SOM-1122 appeared to be due to an interaction of the agonist with beta adrenergic receptors, as they were antagonized by propranolol. The behavioral changes produced by stimulation of beta adrenergic receptors with SOM-1122 were generally similar to those caused by other centrally acting beta adrenergic agonists and by antidepressant drugs. PMID- 2899169 TI - Regulation of the metabolism of striatal dynorphin by the dopaminergic system. AB - The purpose of this study was to explore the dopaminergic control of the striatonigral dynorphin system. Seven daily injections of a dopamine (DA) agonist, apomorphine (APO, 5 mg/kg, b.i.d., s.c.), caused a significant increase of dynorphin A (1-8)-like immunoreactivity (DN-LI) in the striatum (140% over control) and substantia nigra (41% over control) without changing DN-LI in frontal cortex, hypothalamus and hippocampus. Immunocytochemistry revealed intense dynorphin A (1-17)-like immunostaining in striatal "patch" neurons and striatonigral fibers after APO treatment. In order to understand the mechanism of increase in the peptide level, the abundance of preprodynorphin mRNA was quantified by Northern blot hybridization with a 32P-labeled cRNA probe coding for rat preprodynorphin. Seven daily injections of APO increased the abundance of striatal preprodynorphin mRNA by 60%. In another experiment, rats received a single injection of various doses of APO (0.5-2.5 mg/kg s.c.). Striatal DN-LI was decreased by 15% 1 hr after injection of a dose of 2.5 mg/kg of APO. Seven daily injections or a single injection of D-amphetamine produced effects similar to those elicited by APO. These studies reveal that the nigrostriatal DA system plays an important role in modulating the metabolism of striatonigral dynorphin containing neurons. PMID- 2899170 TI - CGS 19755, a selective and competitive N-methyl-D-aspartate-type excitatory amino acid receptor antagonist. AB - CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylic acid) was found to be a potent, stereospecific inhibitor of N-methyl-D-aspartate (NMDA)-evoked, but not KCl-evoked, [3H] acetylcholine release from slices of the rat striatum. The concentration-response curve to NMDA was shifted to the right by CGS 19755 (pA2 = 5.94), suggesting a competitive interaction with NMDA-type receptors. CGS 19755 inhibited the binding of [3H]-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid to NMDA-type receptors with an IC50 of 50 nM, making it the most potent NMDA-type receptor antagonist reported to date. CGS 19755 failed to interact with 23 other receptor types as assessed by receptor binding, including the quisqualate- and kainate-type excitatory amino acid receptors. In crude P2 fractions, no evidence was obtained to suggest that CGS 19755 is taken up by an active transport system. Furthermore, CGS 19755 failed to affect the uptake of L-[3H]glutamate, or to interact with aconitine-induced inhibition of L-[3H]glutamate uptake, the latter finding suggesting a lack of membrane-stabilizing or local anesthetic properties. CGS 19755 selectively antagonized the excitatory effect of iontophoretically applied NMDA in the red nucleus of the rat without affecting the excitatory effects of quisqualate. CGS 19755 blocked the harmaline-induced increase in cerebellar cyclic GMP levels at a dose of 4 mg/kg i.p. with a duration of action exceeding 2 hr. CGS 19755 inhibited convulsions elicited by maximal electroshock in rat (ED50 = 3.8 mg/kg i.p. 1 hr after administration) and in mouse (ED50 = 2.0 mg/kg i.p. 0.5 hr after administration). Likewise, convulsions elicited by picrotoxin were inhibited by CGS 19755, whereas the compound was relatively weak in protecting against convulsions elicited by pentylenetetrazole or strychnine. CGS 19755 produced retention performance deficits in a dark avoidance task. However, CGS 19755 did not show a unique propensity for learning and memory disruption compared to other anticonvulsants. PMID- 2899171 TI - Presynaptic effects of d-tubocurarine on neurotransmitter release at the neuromuscular junction of the frog. AB - 1. Presynaptic effects of d-tubocurarine on neurotransmitter release were examined at the frog neuromuscular junction, using intracellular and extracellular recording techniques. 2. d-Tubocurarine in concentrations of 10(-7) 10(-6) M decreased the quantal content (m) measured by the coefficient of variation and failure methods. 3. d-Tubocurarine produced a shift to the right of the curve relating log quantal content to log [Ca2+]o without changing the slope. 4. The duration of twin-impulse facilitation was not affected by 5 x 10(-7) M-d tubocurarine. Early facilitation was higher in d-tubocurarine. 5. d-Tubocurarine altered the synaptic delay histogram. The peak of the histogram was shifted to longer delays. Prolongation of the minimal delay was seen in most but not all experiments. 6. These results suggest that d-tubocurarine inhibits release of neurotransmitter by affecting a stage in the process of release, which occurs after the entry of Ca2+ ions. PMID- 2899172 TI - Rate of ingestion by mosquito larvae (Diptera: Culicidae) as a factor in the effectiveness of a bacterial stomach toxin. PMID- 2899173 TI - What happened to the RN First Assistant Bill? PMID- 2899174 TI - Engineering, mosquitoes and filariasis: a case report. AB - The results of larval surveys were used to assess the relative numbers of mosquitoes breeding in different types of habitat and in different parts of the town of Pondicherry, India. The results illustrate an effective method to set priorities for mosquito control by identifying the most significant breeding sites in a town, and show that they are not necessarily the most obvious, the most extensive or those intuitively most likely. PMID- 2899175 TI - Analyses of frequency of infection, specific infectivity, and prion protein biosynthesis in scrapie-infected neuroblastoma cell clones. AB - Scrapie, a spongiform encephalopathy of sheep and goats, is caused by a poorly understood transmissible agent in which no nucleic acid has been conclusively identified. Biochemical characterization of agent derived from animal tissues has not been precise because of the tenacious association of the agent with tissue components. As an approach toward obtaining homogeneous preparations of agent generated in vitro, we cloned scrapie-infected neuroblastoma cells. By frequency analysis, nearly every cell in expanded cultures contained scrapie agent. We also analyzed cell-dose infectivity relationships and developed a standard curve which allowed various cultures to be compared. Since a proteinase K (PK)-resistant form of a protein designated prion protein (PrP) has been found in partially purified preparations of scrapie agent from infected animal spleens and brains, we sought to identify this protein in cell cultures. No PK-resistant PrP was found in infected or uninfected cultures, although the PK-sensitive PrP was readily detected. These results suggested that PK-resistant PrP may not be an essential component of the infectious scrapie agent. PMID- 2899177 TI - Acute effect of TRH, flunarizine, lithium and zotepine on amygdaloid kindled seizures induced with low-frequency stimulation. AB - We assessed the acute effects of various drugs on amygdaloid kindled seizures induced with low-frequency stimulations. We used the number of stimulating pulses required for the induction of epileptic afterdischarge (pulse-number threshold; PNT) as an indicator of the seizure generating threshold and the duration of induced seizures (AD duration; ADD) as an indicator of the seizures. TRH increased the PNT without affecting the ADD at a high dose (1.2 mg/kg). Flunarizine decreased the PNT and ADD simultaneously at a high dose (50 mg/kg). Lithium increased the PNT without affecting the ADD at two doses (100 mg/kg, 200 mg/kg). Zotepine decreased the PNT without affecting the ADD at two doses (8 mg/kg, 16 mg/kg). We propose that the technique of low-frequency kindling is a useful experimental model in assessing the effects of antipsychotic or antiepileptic drugs on the excitability of the limbic regions. PMID- 2899176 TI - Human T-cell leukemia virus type I infection of CD4+ or CD8+ cytotoxic T-cell clones results in immortalization with retention of antigen specificity. AB - The human T-cell leukemia virus type I (HTLV-I) is capable of chronically infecting various types of T cells and nonlymphoid cells. The effects of chronic infection on the specific functional activities and growth requirements of mature cytotoxic T lymphocytes (CTL) have remained poorly defined. We have, therefore, investigated the results of HTLV-I infection of both CD4+ and CD8+ human CTL clones. HTLV-I infection resulted in the establishment of functional CTL lines which propagated indefinitely in culture many months longer than the uninfected parental clone. The infected cells became independent of the need for antigen (target cell) stimulation as a requirement for proliferation and growth. Like their uninfected counterparts, however, these HTLV-I-infected clones remained strictly dependent on conditioned medium from mitogen-stimulated T lymphocytes for their growth. This growth factor requirement was not fulfilled by recombinant interleukin-2 alone. Furthermore, the infected lines remained functionally identical to their uninfected parental CTL clones in their ability to specifically recognize and lyse the appropriate target cells. Our findings indicate that the major effects of HTLV-I infection on mature CTL consist of (i) the capacity for proliferation in the absence of antigen stimulation and (ii) a prolonged or immortal survival in vitro, but they also indicate that the fine specificity and cytolytic capacity of these cells remain unaffected. PMID- 2899178 TI - [Effect of the Russian alpha-adrenergic blockader tropafen on the coagulative and rheological properties of the blood in patients with acute myocardial infarction]. PMID- 2899179 TI - [Pathogenesis of pain in the cardiac area in patients with neurocirculatory asthenia and the problems of its treatment]. PMID- 2899180 TI - [Urocaninase activity of the blood of patients with decompensated diabetes mellitus]. PMID- 2899181 TI - Determination of beta adrenoceptor density on rabbit mononuclear leukocytes. AB - The purpose of the present study was to devise a technique for the isolation of a relatively homogeneous mononuclear leukocyte (MNL) preparation from rabbit whole blood and determine the density and affinity of beta-adrenoceptors on MNL. A modified method based upon that by Boyum was developed to maximize isolation of MNL from red blood cells (RBC), granulocytes, and platelets. The method involved an initial centrifugation to remove platelets and two centrifugations with a Ficoll solution to eliminate RBC and granulocytes. beta-Adrenoceptor density as determined with [125I]cyanopindolol and MNL membrane or whole cell preparations ranged between 317 and 360 sites per cell. Affinity for the binding sites was dependent upon whether membrane or whole cell preparations were studied, being 56.3 +/- 9.9 and 11.4 +/- 1.4 pM, respectively. Binding sites were found to be saturable and noncooperative. In addition, the binding sites demonstrated selectivity and stereospecificity for beta-adrenoceptor ligands. It is concluded that the modified method of harvesting MNL from rabbit whole blood provides a relatively homogeneous cell suspension that can be used to study the beta adrenoceptor system. PMID- 2899182 TI - Membrane transferrin receptor (TfR) and nuclear proliferation-associated Ki-67 expression in hemopoietic malignancies. AB - The expression of membrane transferrin receptors (TfRs), as defined by monoclonal antibody OKT9, and the nuclear proliferation-associated antigen Ki-67 were examined in 159 cases of hematological malignancy. Of the "chronic" B and T cell leukemias studied (n = 85), 61% showed less than 5% OKT9-positive cells and only 7% of cases were TfR+ (defined as greater than 20% positive cells). For comparison, the acute leukemias (n = 62) showed higher (p less than 0.001) TfR expression with 39% TfR+ cases, although there was considerable variation within diagnostic subgroups. Nuclear Ki-67 expression was generally insignificant (less than 1%) in chronic leukemias (78 of 88 cases), although two of eight B cell-type prolymphocytic leukemia and four of four cases of plasma cell leukemia showed greater than 10% Ki-67+ components. In contrast, 47% (31 of 66) acute leukemias had greater than 10% Ki-67+ cells, although there appeared to be no relationship between Ki-67 expression and leukemic type. Combined assessments of TfR and Ki-67 expression revealed a Ki-67- TfR- phenotype in 82% of chronic leukemias, compared with 28% of acute type, and a Ki-67+ TfR+ pattern was found in 27% of acute proliferations but not in any case of chronic leukemia. The determination of membrane TfR expression appears to have little value in the diagnostic differentiation of leukemias, whereas Ki-67 is considered to be a useful supplementary investigation in defining high grade tumors, in the recognition of prognostically poor cases of otherwise well defined low grade malignancy, and of potential value in resolving discrepancies between morphological and immunophenotypic features in leukemias of "intermediate" type. PMID- 2899183 TI - Quantitative and qualitative enzyme studies of Hodgkin's disease-derived cell lines. AB - Any extensive analysis of Hodgkin (H) and Reed-Sternberg (RS) cells is limited by the scarcity of available material and by the common contamination with "by stander" cells. The establishment of Hodgkin's disease-derived cell lines provides the opportunity to undertake studies in which large numbers of cells are required, as these cell lines are by definition monoclonal populations with unlimited cell growth. In this study, we analyzed the enzyme profiles of eight Hodgkin's disease cell lines (Co, Ho, Fox, HDLM-2, KM-H2, L428, L540, and L591) whereby cellular alpha-naphthyl acetate esterases, acid phosphatases, and dipeptidylpeptidase IV were examined quantitatively or qualitatively by IEF or chromatographic techniques. The results indicate that all of the H-RS cell lines examined had enzymatic features typical for lymphoid cells and, in particular, a monocyte/histiocyte origin of the cell lines could be excluded. Extrapolation of the available immunological, molecular biological, and enzymological evidence gained in vitro on cultured representatives of H-RS cells suggests a lymphoid origin for in vivo H-RS cells. PMID- 2899184 TI - Molecular/cytogenetic alterations accompanying the development of multidrug resistance in the J774.2 murine cell line. AB - Mouse macrophage-like J774.2 cells were selected for resistance to colchicine and examined by molecular/cytogenetic analysis to determine whether the acquisition of the multidrug resistant (mdr) phenotype was associated with specific chromosomal rearrangements. Cytogenetic studies of the J774.2 parental and two colchicine-resistant (CLCR) sublines--J7.Cl-30 (770-fold CLCR) and J7.Cl-100 (2500-fold CLCR)--demonstrated specific numeric and structural karyotypic alterations accompanying the emergence of mdr. The parental cells demonstrated a modal chromosome number of 63, while the modal number of the J7.Cl-30 subline was 53. The most striking difference between the parental and J7.Cl-30 subline was the presence of an average of 60 double minutes (DMs) per cell in the CLCR cells. The 2500-fold resistant J7.Cl-100 subline displayed a modal number of 50, which included structural rearrangements involving chromosomes 2 and 7 and concomitant replacement of DMs by a homogeneously staining region (HSR). Southern blotting analysis demonstrated a approximately 35-fold amplification of P-glycoprotein homologous sequences in the J7.Cl-30 subline and approximately 70-fold amplification in the J7.Cl-100 subline. Chromosomal in situ hybridization localized the amplified P-glycoprotein sequences to DMs (J7.Cl-30) and the HSR (J7.Cl-100) in these CLCR sublines. Our results suggest that CLCR in J774.2 cells results from overexpression of P-glycoprotein via gene amplification which was accompanied by chromosomal evolution from DMs to an HSR. PMID- 2899185 TI - Management of patients on psychotropic drugs in primary care clinics. AB - While nonpsychiatrist physicians account for the majority of prescriptions written for psychotropic drugs, little is known about the quality of their drug management strategy. We studied this issue using data from 16 academic internal medicine group practices. Data on treatment, abstracted from medical records, were compared to criteria for quality care. Eighteen percent of patients used minor tranquilizers or antidepressants. The only individual factor independently associated with use of minor tranquilizers was mental health status. Nonwhites were less likely than whites to be diagnosed as depressed or receive antidepressants, even after controlling for baseline mental and physical health status. Mental and physical health status were also independently associated with antidepressant drug use. Quality of care was low for formulating a treatment plan for either drug group and for follow-up plans for antidepressants. Documentation of an adequate treatment plan for minor tranquilizers was poorest for patients who visited a house staff or nonphysician rather than a faculty member. For antidepressants, the patients with the poorest general health status tended to have the best documentation of treatment plans. PMID- 2899186 TI - The Northwick Park "functional" psychosis study: diagnosis and treatment response. AB - Functional psychosis is conventionally subdivided into schizophrenia and manic depressive psychosis. Response to treatment is assumed to be a validating criterion for these diagnoses. The efficacy of pimozide (a dopamine antagonist neuroleptic), lithium, and a combination of the two was compared with that of placebo in a 4 week trial in 120 functionally psychotic patients each of whom was assessed for psychotic symptoms, manic symptoms, and depressive symptoms. The sample was subdivided into patients with predominantly elevated mood, predominantly depressed mood, and no consistent mood change. Pimozide reduced psychotic symptoms in all groups of patients. The only significant effect of lithium was to reduce elevated mood. Thus dopamine blockade seems relevant to the resolution of psychotic symptoms in all types of "functional" psychosis but the mode of action of lithium in psychotic patients concerns only mood. Application of standardised classifications of functional psychosis to these data did not change this conclusion. PMID- 2899187 TI - Evaluation of simple clinical signs for the diagnosis of acute lower respiratory tract infection. AB - The reliability of clinical signs that might be used by village health workers in distinguishing acute lower respiratory infection (LRI) from upper respiratory infections (URI) in children was evaluated. 142 infants and 108 preschool children with LRI and 151 infants and 281 preschool children with URI, attending hospital, were studied. Respiratory rates of over 50/min in infants and over 40/min in children 12-35 months of age, as well as a history of rapid breathing and the presence of chest retractions in both age groups, were found to be sensitive and specific indicators of LRI. Increased respiratory rates and history of rapid breathing were also sensitive in diagnosis of less severe LRI that did not necessitate admission to the wards, whereas chest retraction was not. All these clinical signs had a low sensitivity in diagnosing LRI in children aged 36 months and over. PMID- 2899189 TI - Symptomatic cytomegalovirus infection in seropositive kidney recipients: reinfection with donor virus rather than reactivation of recipient virus. AB - 74 patients receiving cadaver kidney grafts were investigated prospectively for cytomegalovirus (CMV) infection. Among seropositive recipients CMV infection, especially symptomatic and disseminated infection, occurred significantly more frequently when kidneys came from seropositive than from seronegative donors. Since seropositive recipients can become infected with donor virus, the excess is probably accounted for by reinfection. This conclusion was supported by restriction enzyme typing of virus isolates from recipient pairs receiving kidneys from the same donor; proven reinfection with donor strain virus was significantly commoner than proven reactivation of recipient virus. Furthermore, symptoms occurred only in the proven reinfection group. Although the proportion of reinfections that caused symptoms was less than that seen in primary infections, prior natural infection with CMV clearly does not prevent symptomatic reinfection in seropositive recipients, a point which has profound implications for future vaccination strategies in renal allograft recipients and choice of donors. PMID- 2899190 TI - Encapsulation of tumours as a modified wound healing response. AB - Tumour capsules may arise as the result of a modified wound healing response, consequent upon disturbance of the normal tissue architecture caused by an expanding tumour. PMID- 2899188 TI - Effect of a low-fat high-carbohydrate diet on symptoms of cyclical mastopathy. AB - 21 patients with severe persistent cyclical mastopathy of at least 5 years' duration were randomised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15% of calories while increasing complex carbohydrate consumption to maintain caloric intake. Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels. Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen. After 6 months there was a significant reduction in the intervention group in the severity of premenstrual breast tenderness and swelling. Physical examination showed reduced breast swelling, tenderness, and nodularity in 6 of 10 patients in the intervention group and 2 of 9 patients in the control group. PMID- 2899191 TI - Child abuse after Cleveland. PMID- 2899192 TI - Midazolam--is antagonism justified? PMID- 2899193 TI - What causes cerebral palsy? PMID- 2899194 TI - HIV infection, breastfeeding, and human milk banking. PMID- 2899195 TI - Preventing travellers' diarrhoea. PMID- 2899196 TI - Impact of the National Control of Diarrhoeal Diseases Project on infant and child mortality in Dakahlia, Egypt. National Control of Diarrheal Diseases Project. AB - The Egyptian National Control of Diarrheal Diseases Project (NCDDP) started in 1983. A field trial done in Dakahlia Governorate in 1980 to promote oral rehydration therapy showed that the mortality rate for the under-fives during the diarrhoea season was 18.1/1000 in control villages and 10.5/1000 in "outreach" villages (p less than 0.001). In 1986 mortality rates had become similar in the two areas and lower than in 1980 (6.5/1000 and 6.0/1000, respectively), even though there were no significant changes in diarrhoea incidence. Virtually all the reduction in mortality was due to a decline in diarrhoea-associated deaths. The principal differences between 1986 and 1980 were better case-management by mothers and doctors, in both outreach and control villages, and far greater television ownership. Village civil registers showed only slight changes in under five mortality from all causes after 1980, but an accelerating decline from 1983. Governorate-wide civil registration data showed slowly falling infant death rates from 1970 onward, accelerating after 1982, with most of the decline corresponding to the seasonal pattern of diarrhoea-associated mortality throughout the year. Thus NCDDP promotion of better treatment seems to have been responsible for the decline in mortality. PMID- 2899197 TI - Dracunculiasis eradication: the tide has turned. PMID- 2899198 TI - Continuous arteriovenous haemodialysis in critically ill patients. AB - Continuous arteriovenous haemodialysis (CAVHD) is a new treatment for critically ill patients with renal failure that combines convective and diffusive solute removal. The clearance of urea (14.8-22.1 ml/min) is sufficient to achieve a steady-state urea concentration of 22 mmol/l, even in patients with a high catabolic rate and cardiovascular instability. The technique is simple and does not involve the use of blood pumps or specialised staff. Initial experience in 36 critically ill patients with renal failure indicates that it is safe and reliable, with less associated morbidity than other techniques. PMID- 2899199 TI - Prevention of disease in the poor world. PMID- 2899200 TI - Ethical and medical considerations for a blood donation programme in a refugee population. PMID- 2899201 TI - Psychiatric profile of shoplifters. PMID- 2899202 TI - Skin absorption of lead. PMID- 2899203 TI - Reversible chorea due to ranitidine and cimetidine. PMID- 2899204 TI - Treatment of Budd-Chiari syndrome by percutaneous transluminal angioplasty. PMID- 2899205 TI - Hypnotherapy for duodenal ulcer. PMID- 2899206 TI - Viruses of enterically transmitted non-A, non-B hepatitis. PMID- 2899207 TI - Airway hyperreactivity. PMID- 2899208 TI - Influence of inhaled terbutaline on bronchial responsiveness. PMID- 2899209 TI - Sustained effects of oestrogen implant overdose. PMID- 2899210 TI - Implantation of embryos after partial opening of oocyte zona pellucida to facilitate sperm penetration. PMID- 2899211 TI - Monitoring of cyclosporin by monoclonal radioimmunoassay in cardiac transplantation. PMID- 2899212 TI - Serological discrimination between HIV-1 and HIV-2. PMID- 2899213 TI - AIDS in sub-Saharan Africa. PMID- 2899214 TI - Growth in children treated for acute lymphoblastic leukaemia. PMID- 2899215 TI - Treatment of menopausal symptoms in breast cancer patients. PMID- 2899216 TI - Biological differences in the three major leukaemias. PMID- 2899218 TI - Gallstone pancreatitis. PMID- 2899217 TI - Correction of anaemia by desferrioxamine in a patient with alcoholic cirrhosis. PMID- 2899220 TI - Legionnaires' disease. PMID- 2899219 TI - Deterioration in primary biliary cirrhosis in patient on ursodeoxycholic acid. PMID- 2899221 TI - Variation in antibody isotype responses in clinically covert toxocariasis. PMID- 2899222 TI - Neonatal intensive care: trends in morbidity. PMID- 2899223 TI - Resource allocation review. PMID- 2899225 TI - Child abuse registers. PMID- 2899226 TI - Alpha-interferon in thrombocytopenic purpura. PMID- 2899224 TI - Avoidable deaths. PMID- 2899228 TI - Torsade de pointes and Q-T prolongation in secondary hypothyroidism. PMID- 2899227 TI - Impaired ability of peroxisomes to activate very-long-chain fatty acids in X linked adrenoleukodystrophy. PMID- 2899229 TI - T waves in long Q-T syndromes. PMID- 2899230 TI - Screening for early ovarian cancer. PMID- 2899232 TI - Extreme labile blood pressure in Guillain-Barre syndrome. PMID- 2899231 TI - Mechanism of nitrate vasodilators. PMID- 2899233 TI - Occupational cancer and radiation. PMID- 2899234 TI - The Nottingham study of neurotic disorder: comparison of drug and psychological treatments. AB - 210 psychiatric outpatients with generalised anxiety disorder (71), or panic disorder (74), or dysthymic disorder (65) diagnosed by an interview schedule for DSM-III were allocated by constrained randomisation to one of five treatments: diazepam (28), dothiepin (28), placebo (28), cognitive and behaviour therapy (84), and a self-help treatment programme (42). All treatments were given for 6 weeks and then withdrawn by 10 weeks. Ratings of psychopathology were made by psychiatric assessors blind to both treatment and diagnosis before treatment and at 2, 4, 6, and 10 weeks after randomisation. 18 patients had insufficient data for analysis because of early drop-out. There were no important differences in treatment response between the diagnostic groups, but diazepam was less effective than dothiepin, cognitive and behaviour therapy, or self-help, these three treatments being of similar efficacy. Significantly more patients in the placebo group took additional psychotropic drugs in the 10 week period, and those allocated to dothiepin and cognitive and behaviour therapy took the least. PMID- 2899235 TI - Association of Ureaplasma urealyticum infection of the lower respiratory tract with chronic lung disease and death in very-low-birth-weight infants. AB - Endotracheal aspirates from 200 infants who weighted less than or equal to 2500 g and who had evidence of respiratory disease were cultured within 24 h of birth for mycoplasmas, chlamydiae, viruses, and bacteria to evaluate the relation between lower respiratory tract infection and development of chronic lung disease and/or death. Ureaplasma urealyticum, an organism not visible on gram stain, not recovered on routine bacteriological media, and not susceptible to antibiotics commonly used to treat neonatal infections, was the single most common organism isolated. 14% of isolates were from infants born by caesarean section with intact membranes, which indicated that infection had occurred in utero. The findings probably represented true infection of the lower respiratory tract because the organism was recovered in pure culture in numbers greater than 10(3) from 85% of the infants, and also from the blood in 26% of infants. Those infants less than or equal to 1000 g with Ureaplasma urealyticum infection of the lower respiratory tract were twice more likely to have chronic lung disease or to die than were infants of similar birth-weight but who were uninfected, or infants greater than 1000 g. Very-low-birth-weight infants infected with ureaplasmas did not differ from those uninfected, either in demographic features or in potential risk factors for chronic lung disease. PMID- 2899236 TI - Effects of intermittent treatment with aspirin on thromboxane and prostacyclin formation in patients with acute myocardial infarction. AB - Thromboxane and prostacyclin formation were monitored in twenty patients with acute myocardial infarction. Ten received 500 mg acetylsalicylic acid (ASA) orally starting 12 h after admission and then intermittently every third day for one month; the other ten did not receive ASA or any other drug known to interfere with the synthesis of prostanoids. In the ASA group thromboxane formation, initially raised, fell rapidly and remained low. In the control group thromboxane formation decreased very slowly and was not normal by the end of the study period. Prostacyclin formation seemed identical in the two groups. Thus intermittent ASA, in this dosage, efficiently inhibited the enhanced thromboxane formation in acute myocardial infarction without interfering with prostacyclin formation. PMID- 2899237 TI - Efficacy of multiple-dose halofantrine in treatment of chloroquine-resistant falciparum malaria in children in Kenya. AB - Halofantrine hydrochloride given to 46 Kenyan children with falciparum malaria at 10 mg/kg for two doses, and to 60 other children at 8 mg/kg for three doses, resulted in rapid parasite clearance, mean parasite clearance times being 45.4 h and 54.8 h, respectively. In-vitro chemosensitivity tests showed that most infections were due to chloroquine-resistant parasites, and that parasite maturation was inhibited by considerably lower concentrations of halofantrine than of chloroquine. PMID- 2899238 TI - Clinical trials with halofantrine hydrochloride in Malawi. AB - Two clinical trials of the phenanthrene methanol compound halofantrine in the treatment of Plasmodium falciparum were conducted in Malawi, in areas where the parasite was known to be chloroquine resistant. In the first trial all 46 patients had symptoms of malaria and parasite densities ranging from 2500/microliter to 212,000/microliter. They were given a single dose of halofantrine hydrochloride, 16 mg/kg body weight. The recrudescence rate on day 14 of follow up was unacceptably high (38%). In the second trial the dose given was 8 mg/kg 6 hourly for three doses. Of the 49 children followed up for 14 days, 47 became aparasitaemic--ie, the cure rate was 96%. In both trials the drug was very well tolerated. Halofantrine hydrochloride seems to be effective against P falciparum chloroquine sensitive and resistant strains in Africa. PMID- 2899239 TI - Prevention of exercise-induced bronchoconstriction by inhaled frusemide. AB - To determine whether inhaled frusemide, a diuretic able to interfere with ion and water movement across airway epithelium, can modify exercise-induced bronchoconstriction, a three-part randomised, double-blind, placebo-controlled study was done in asthmatic patients who had a fall in FEV1 of at least 20% after running up and down a corridor. In the first part the effect of approximately 28 mg frusemide given as an aerosol was compared with that of a placebo. In the second part two doses of inhaled frusemide (approximately 14 mg and 28 mg) were examined. In the third part the effect of 20 mg oral frusemide was tested. Inhaled frusemide had a good and dose-related protective effect, whereas oral frusemide was ineffective. The mean (95% CI) maximum percentage falls in the FEV1 were: 11.5 (14.3-8.7) with frusemide and 33.8 (39.1-28.5) with placebo in the first part of the study; 13.6 (21.6-6.0) with 28 mg frusemide, 19.7 (28.2-11.3) with 14 mg frusemide, and 34.6 (39.4-30.0) with placebo in the second part of the study; and 15.2 (19.9-10.5) with inhaled frusemide, 38.2 (47.1-29.3) with oral frusemide, and 35.3 (45.9-24.7) with placebo in the last part of the study. The findings lend support to the hyperosmolarity hypothesis of exercise-induced asthma and may have therapeutic implications. PMID- 2899240 TI - Measurement of cardiac output. PMID- 2899241 TI - Kava. PMID- 2899242 TI - Another shock to the system for the NHS? PMID- 2899243 TI - Gastro-oesophageal reflux and apparent life-threatening events in infancy. PMID- 2899244 TI - Obesity and the autonomic nervous system. PMID- 2899246 TI - Trends in dental health of ten-year-old school children in south-west Scotland after cessation of water fluoridation. AB - The prevalence of dental caries in 10-year-old children in Stranraer has increased since the withdrawal of water fluoridation, with a 115% increase in the mean cost of restorative dental work due to caries and a 21% increase in the mean cost of all dental treatment. In Annan, a similar town which has never had fluoride added to the water supply, caries prevalence fell significantly, with little change in the cost of dental treatment. The findings suggest an association between cessation of water fluoridation and the increased prevalence of caries in Stranraer children. PMID- 2899245 TI - Candida and AIDS: evidence for protective antibody. AB - Clinical observation and animal models of candidosis suggest that, although T lymphocytes are important in preventing superficial candidosis, defence against systemic candidosis depends upon humoral immunity. An antibody response to the immunodominant 47 kD antigen of Candida albicans is invariably associated with recovery. The presence of this antibody in patients with chronic mucocutaneous candidosis and the acquired immunodeficiency syndrome (AIDS) could account for the rarity of disseminated candidal infection in these conditions. Polyclonal B cell activation may be responsible for the frequency with which this antibody is produced in AIDS. Antibody to the 47 kD antigen could be useful in the treatment and prevention of systemic candidosis, though not in the superficial candidosis of AIDS. PMID- 2899247 TI - Physicians, triage, and nuclear war. PMID- 2899248 TI - Exploding head syndrome. PMID- 2899249 TI - Antiphospholipid antibodies and thrombosis. PMID- 2899251 TI - Prosthetic heart-valve occlusion. PMID- 2899250 TI - Treatment of systemic lupus erythematosus by extracorporeal immunoadsorption. PMID- 2899252 TI - Near-pure xylene causing reversible neuropsychiatric disturbance. PMID- 2899254 TI - Cryoglobulinaemia and alpha-interferon. PMID- 2899253 TI - Seroconversion against human herpesvirus-6 (and other herpesviruses) and clinical illness. PMID- 2899255 TI - H2-receptor antagonist non-responders. PMID- 2899256 TI - Management of ruptured and unruptured ectopic pregnancies by videopelviscopy. PMID- 2899257 TI - Management of unruptured tubal pregnancy by aspiration of sac under ultrasound control. PMID- 2899259 TI - Treatment of severe hypercalcaemia with mithramycin and aminohydroxypropylidene bisphosphonate. PMID- 2899258 TI - Renal failure during dissolution of gallstones by methyl-tert-butyl ether. PMID- 2899260 TI - HIV infection, breastfeeding, and human milk banking. PMID- 2899261 TI - Polymerase chain reaction and in-vitro antibody production for early diagnosis of paediatric HIV infection. PMID- 2899262 TI - In-vitro secretion of HIV-specific antibodies by peripheral blood cells. PMID- 2899263 TI - Myelopathy after stopping zidovudine. PMID- 2899264 TI - Genetic recombination between tuberous sclerosis and oncogene v-abl. PMID- 2899265 TI - Cibenzoline and hypoglycaemia. PMID- 2899266 TI - Listeriosis associated with antithymocyte globulin treatment. PMID- 2899267 TI - Optochin-resistant Streptococcus pneumoniae. PMID- 2899268 TI - Quinolones and multiresistant Plasmodium falciparum. PMID- 2899269 TI - Scintigraphic demonstration of myocardial ischaemia. PMID- 2899270 TI - New approach to capitation fees. PMID- 2899271 TI - Notifying drug addicts. PMID- 2899272 TI - Prevention of disease in the Third World. PMID- 2899273 TI - Remedies for Third World diseases. PMID- 2899274 TI - Alcohol intake in the UK. PMID- 2899276 TI - Rapids, rafts, and rats. PMID- 2899275 TI - Strategies for control of malaria in Africa. PMID- 2899277 TI - Fetal blood sampling in investigation of chromosome mosaicism in amniotic fluid cell culture. PMID- 2899278 TI - Non-tuberculous mycobacteria in gastrointestinal biopsy specimens. PMID- 2899279 TI - Cyclosporin and erythraemia. PMID- 2899280 TI - Dietary fatty acids and ischaemic arrhythmias. PMID- 2899281 TI - Haemochromatosis screening. PMID- 2899282 TI - Will falling death rates from acute and chronic bronchitis continue? PMID- 2899283 TI - Childhood leukaemia and Dounreay. PMID- 2899284 TI - Import of psittacine birds and chlamydial infections in Finland. PMID- 2899285 TI - Galactosylation of IgG associated oligosaccharides. PMID- 2899287 TI - Mitochondrial dysfunction, energy expenditure, and cystic fibrosis. PMID- 2899286 TI - Bleeding in renal failure. PMID- 2899288 TI - Global AIDS figures. PMID- 2899290 TI - [Regulation of the transcription of the tyrosine aminotransferase gene by glucocorticoids in Morris hepatoma 7777 and 8994 cells]. AB - Kinetics of tyrosine aminotransferase (TAT) mRNA synthesis in Morris rat hepatoma cell lines 7777 and 8994 after dexamethasone treatment (10(-7) M) was studied by molecular hybridization of the RNA with cloned fragments of TAT gene from rat liver cells. It was demonstrated that initiation of TAT gene transcription increased 20 minutes after glucocorticoid treatment. The level of TAT mRNA was not induced by dexamethasone in rat hepatoma cell line 8994. Actinomycin D prevented the deinduction of TAT by stabilization of TAT mRNA. PMID- 2899291 TI - The diffuse neuroendocrine system: a molecular perspective. AB - This review seeks to illustrate that the concept of a 'diffuse neuroendocrine system' arises from a series of ontogenetic, phylogenetic and functional overlaps borne out at the molecular level, which engender an apparent global unit. Extrapolation from the overlaps should lead to the discovery of new facets in the relationships between molecular components of the DNES, and this approach will lead to a spectrum of markers and probes with a variety of clinical applications. Initial approaches progressed from cellular function toward molecular anatomy, but converse questions starting from anatomical markers are now arising. PMID- 2899289 TI - Asthma in the elderly: a brief report. AB - Asthma in the elderly may present difficult management problems. We reviewed 46 elderly patients with corticosteroid dependent asthma who have been managed on our ambulatory service for an average of nine years. We present our therapeutic regimens which resulted in better control for the majority of patients. The goals of therapy were control of asthma to prevent status asthmaticus which is potentially fatal asthma. In those patients who did not improve, inability to comply with our regimens was a major factor. PMID- 2899292 TI - Progressive destructive mycetoma caused by Madurella mycetomi. PMID- 2899293 TI - Infection with human T-cell leukemia virus type I in patients with leukemia. PMID- 2899294 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 31-1988. A 51-year-old man with fever, painful legs, and a rash. PMID- 2899295 TI - Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease. AB - In idiopathic Parkinson's disease massive cell death occurs in the dopamine containing substantia nigra. A link between the vulnerability of nigral neurons and the prominent pigmentation of the substantia nigra, though long suspected, has not been proved. This possibility is supported by evidence that N-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite MPP+, the latter of which causes destruction of nigral neurons, bind to neuromelanin. We have directly tested this hypothesis by a quantitative analysis of neuromelanin pigmented neurons in control and parkinsonian midbrains. The findings demonstrate first that the dopamine-containing cell groups of the normal human midbrain differ markedly from each other in the percentage of neuromelanin-pigmented neurons they contain. Second, the estimated cell loss in these cell groups in Parkinson's disease is directly correlated (r = 0.97, P = 0.0057) with the percentage of neuromelanin-pigmented neurons normally present in them. Third, within each cell group in the Parkinson's brains, there is greater relative sparing of non-pigmented than of neuromelanin-pigmented neurons. This evidence suggests a selective vulnerability of the neuromelanin-pigmented subpopulation of dopamine-containing mesencephalic neurons in Parkinson's disease. PMID- 2899296 TI - Augmentation of the indirect sympathomimetic action of tyramine by cardioactive steroids is a consequence of elevated intracellular sodium. AB - The augmentation by the cardioactive steroid acetylstrophanthidin of neurotransmitter release evoked by tyramine, and the dependence of the augmentation upon Na+, has been investigated in dog saphenous vein rings in which monoamine oxidase activity and uptake2 had been inhibited with pargyline and corticosterone respectively. High extracellular Na+ (Nao; 263 mmol/l) reduced basal efflux of 3H-compounds from the rings and also reduced tyramine-evoked efflux. Low Nao (25 mmol/l) increased basal efflux of 3H but reduced tyramine evoked efflux. The increment in basal 3H-efflux caused by low Nao was cocaine sensitive. A presumed increase in intracellular Na+ (Nai), produced by preincubating rings with acetylstrophanthidin in normal (143 mmol/l) or high Nao, augmented 3H-efflux evoked by subsequent incubation with tyramine in normal Nao. Pre-incubating rings with acetylstrophanthidin in low Nao, conditions which would not be expected to increase Nai, did not cause augmentation of the subsequent tyramine-evoked 3H-efflux. An increase in Nai, produced either as above or by pre incubating rings in high Nao alone, reduced subsequent neuronal 14C-tyramine uptake. Low Nao present only during incubation reduced neuronal 14C-tyramine uptake, but high Nao present only during incubation did not increase neuronal 14C tyramine uptake from that measured in normal Nao. The data are consistent with the following hypotheses: that tyramine uptake is dependent upon the prevailing inwardly directed Na+-gradient, that consequent noradrenaline efflux is Na+ gradient dependent and that the enhancement by acetylstrophanthidin of tyramine evoked 3H-efflux is a consequence of the raised Nai caused by Na+,K+-ATPase inhibition. PMID- 2899297 TI - Octreotide: Jack-of-all-trades or expensive orphan? PMID- 2899298 TI - Successful treatment of ophthalmoplegia in acromegaly with the somatostatin analogue SMS 201-995. PMID- 2899299 TI - Closure of a high-output external pancreatic fistula by SMS 201-995, a long acting analogue of somatostatin. PMID- 2899300 TI - Selective damage in striatum and hippocampus with in vitro anoxia. AB - An in vitro model of anoxia-induced brain damage was utilized to help elucidate the biochemical basis of cell damage due to reduced oxygen availability. Previous studies suggest that anoxia-induced damage may vary presynaptically, post synaptically or in the cell body. Thus, the consequences of an anoxic treatment incubation were examined with hippocampal slices, which contain cholinergic nerve terminals but not cell bodies, and with slices from whole striatum or its subregions, which contain both cholinergic cell bodies and nerve terminals. Slices were preincubated with either oxygen or nitrogen (treatment incubation) and the persistent effects of this treatment on [14C]acetylcholine and 14CO2 production from [U-14C]glucose were assessed in a subsequent incubation under optimal conditions (test incubation). An anoxic treatment incubation reduced the subsequent test incubation production of CO2 about 40% in the hippocampus and striatum. The anoxic treatment incubation diminished ACh production by 46% in the striatum, but only minimally affected that in the hippocampus. Anoxic treatment incubations of synaptosomes did not alter test-incubation ACh synthesis or CO2 production. Omission of calcium from the anoxic treatment incubation increased striatal ACh synthesis by 88% and CO2 production in both regions. These results suggest that anoxia produces persistent changes in postsynaptic processes or cell bodies (in this model cholinergic ones) that differ from those in nerve terminals and that calcium is important in the production of these deficits. PMID- 2899301 TI - Glutaminase in neurons and astrocytes cultured from mouse brain: kinetic properties and effects of phosphate, glutamate, and ammonia. AB - Phosphate activated glutaminase comprises two kinetically distinguishable enzyme forms in cultures of cerebellar granule cells, of cortical neurons and of astrocytes. Specific activity of glutaminase is higher in cultured neurons compared with astrocytes. Glutaminase is activated by phosphate in all cell types investigated, however, glutaminase in astrocytes requires a much higher concentration of phosphate for half maximal activation. One of the products, glutamate, inhibits the enzyme strongly, whereas the other product ammonia has only a slight inhibitory action on the enzyme. PMID- 2899302 TI - Application of serial sampling of cerebrospinal fluid in pharmacodynamic studies with a drug active in the CNS: heptabarbital concentrations at onset and offset of loss of righting reflex in rats. AB - As cerebrospinal fluid (CSF) possesses unique characteristics in order to explore concentration-pharmacological response relationships of drugs active in the CNS, the practicability of serial sampling of CSF was tested in a study with heptabarbital. Concentrations in CSF and plasma were measured simultaneously in individual rats during and after an intravenous infusion for 30 min. At the end of the infusion, the distribution equilibrium was attained with a CSF/plasma concentration ratio of 0.38, roughly equal to the fraction unbound to protein. When concentrations in blood and CSF were determined at the onset and offset of loss of righting reflex concentrations in blood were significantly greater at onset (146 +/- 19 mg/l) than at offset (108 +/- 16 mg/l, n = 6), whereas concentrations in CSF were identical (39 +/- 5 and 38 +/- 5 mg/l, respectively). This confirmed the earlier observation that the CSF is pharmacokinetically indistinguishable from the site of action. When the duration of the loss of righting reflex was varied, concentrations of heptabarbital in CSF at onset and offset were similar, independent of the duration of the loss of righting reflex (1-5 hr). These findings demonstrate the absence of the development of acute tolerance and confirmed that no (inter)active metabolites interfered with the pharmacological response. In a total number of 26 rats the concentrations in CSF at onset and offset of loss of the righting reflex were compared. The interindividual variation was 13-15% and the intra-individual variation was only 4-6%. The results demonstrate the usefulness of serial sampling of CSF in pharmacodynamic studies with centrally acting drugs. PMID- 2899303 TI - The effect of long-term treatment with amine-depleting drugs or chlorpromazine on alpha-adrenoreceptors and 5-HT2 receptors in the brain of the rat. AB - The effect of chlorpromazine, oxypertine, tetrabenazine or reserpine on alpha adrenoreceptors and 5-HT2 receptors in the brain of the rat was studied both in vitro and after the administration to animals for up to 12 months. In vitro, chlorpromazine and oxypertine potently displaced the specific binding of [3H]WB 4101 to alpha 1 adrenoreceptors in the cortex and of [3H]ketanserin to 5-HT2 receptors in the frontal cortex. Both drugs were moderately effective in displacing the specific binding of [3H]clonidine from cortical alpha 2 adrenoreceptors. Tetrabenazine only weakly displaced the specific binding of [3H]WB 4101, [3H] clonidine and [3H]ketanserin. The incorporation of reserpine into tissue incubates had little effect on the binding of any of these ligands. Administration of chlorpromazine (33-36 mg/kg/day) to rats for up to 12 months reduced the number of specific binding sites (Bmax) for [3H]ketanserin in the frontal cortex, but did not alter the specific binding of [3H]WB 4101 or specific [3H]clonidine to cortical membranes. In contrast, treatment with oxypertine (6.3 7.3 mg/kg/day), tetrabenazine (6.0-6.7 mg/kg/day) or reserpine (0.28-0.30 mg/kg/day) increased the Bmax for the specific binding of [3H]WB 4101, but did not alter the specific binding of [3H]clonidine or [3H]ketanserin. Oxypertine resembles chlorpromazine in its ability to interact with alpha-adrenoreceptors and 5-HT2 receptors in brain. Tetrabenazine and reserpine have few direct actions on post-synaptic monoamine receptors. However, on long-term administration, oxypertine, like tetrabenazine and reserpine, predominantly altered alpha 1 adrenoreceptors, whereas chlorpromazine influenced the population of 5-HT2 receptors. PMID- 2899304 TI - Transmitter phenotype is a major determinant in the specificity of synapses formed by cholinergic neurons transplanted to the hippocampus. AB - Embryonic habenular or striatal cholinergic tissues were transplanted to the hippocampal formation of adult rats. The connectivity of these grafts with the host hippocampal formation was analysed using acetylcholinesterase histochemistry and immunocytochemistry with a monoclonal antibody to choline acetyltransferase. Both graft types produced laminar arrangements of acetylcholinesterase-positive fibers in the hippocampal formation that closely resembled the native pattern of cholinergic innervation. In addition, graft-derived choline acetyltransferase immunoreactive synapses were found in the host hippocampal formation. These synapses were formed on non-immunoreactive dendritic structures and were similar to the types of cholinergic synapses found in the hippocampal formation of normal animals. These data indicate that the cholinergic transmitter phenotype is a major determinant of whether a neuron will form typical cholinergic synapses with hippocampal targets. PMID- 2899305 TI - Both synaptic and antidromic stimulation of neurons in the rat superior cervical ganglion acutely increase tyrosine hydroxylase activity. AB - Electrical stimulation of the preganglionic cervical sympathetic trunk produces an acute increase in the rate of DOPA synthesis in the rat superior cervical ganglion. The present study was designed to test the possibility that this acute transsynaptic stimulation of catechol biosynthesis could be, at least in part, a consequence of an increase in the firing rate of the postganglionic sympathetic neurons. For this purpose, the effect of stimulation in vitro of the preganglionic cervical sympathetic trunk was compared to that of stimulation of the predominantly postganglionic internal and external carotid nerves. Stimulation of the cervical sympathetic trunk at 10 Hz for 30 min produced a 4.6 fold increase in DOPA synthesis, while simultaneous stimulation of the two postganglionic trunks produced a 3.1-fold increase. The internal carotid nerve is known to contain a small population of preganglionic fibers that synapse on principal neurons in the ganglion before entering this nerve trunk. To eliminate the possibility that the effect of stimulation of the internal carotid nerve is mediated by synaptic stimulation via these preganglionic "through fibers", the effect of stimulation of previously decentralized ganglia was examined. While decentralization reduced the magnitude of the effect of stimulation of the internal and external carotid nerves, a 2.0-fold increase in DOPA synthesis was still seen. In addition, when these nerve trunks were stimulated in control ganglia that had been maintained in organ culture for 48 h to allow time for the degeneration of afferent nerve terminals, DOPA synthesis increased 4.1 fold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899306 TI - Immunohistochemistry of tyrosine hydroxylase and phenylethanolamine N methyltransferase in the human brain stem: description of adrenergic perikarya and characterization of longitudinal catecholaminergic pathways. AB - Using immunocytochemical method in conjunction with antibodies to tyrosine hydroxylase and phenylethanolamine N-methyltransferase, catecholaminergic cell groups and axon pathways are mapped in the human hind brain. Adrenergic perikarya are located mainly in the rostral medulla, as in lower animals, and contribute a subset of axons to the main longitudinal catecholaminergic bundle which runs through the medulla oblongata, pons and midbrain such as the dorsal part of the central nucleus of the medulla oblongata, the parvocellular reticular formation ventromedial to the facial nerve and ventrolateral to the locus coeruleus. Adrenergic terminals are present in the locus coeruleus and other medullary and pontine structures. The locus coeruleus contains only tyrosine hydroxylase immunoreactive cells and appears to be the source of a discrete dorsal catecholaminergic bundle which runs through the central tegmental field just ventrolateral to the periaqueductal gray of the rostral pons and mesencephalon and which does not contain adrenergic axons. A ventral catecholaminergic bundle arising in the medullary cells does contain a subset of adrenergic axons in the mesencephalic tegmental field. These two longitudinal axon bundles run near each other in the mesencephalic reticular formation. Additional descriptions are provided of catecholaminergic axons near the dorsal and ventral surface of the human medulla. PMID- 2899307 TI - The mode of action of guanidine on mouse motor nerve terminals. AB - The action of guanidine on presynaptic membrane currents has been investigated to elucidate its facilitatory effect on phasic transmitter release at the mouse neuromuscular junction. Guanidine (2-10 mM) produced a near complete inhibition of the fast voltage-dependent K current. This effect is expected to allow an increase in Ca2+ influx and, thereby, in transmitter release upon nerve stimulation. Guanidine failed to block the Ca-dependent K current of the nerve terminals. PMID- 2899308 TI - CNQX blocks acidic amino acid induced depolarizations and synaptic components mediated by non-NMDA receptors in rat hippocampal slices. AB - 6-Cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX; FG 9065) is a new excitatory amino acid antagonist. In the spinal cord it has been reported to selectively block responses to acidic amino acids acting at receptors of the non-N-methyl-D aspartate (non-NMDA) type. Here we report that in rat hippocampal slices bathed in Mg2+-free medium 10 microM CNQX reversibly blocks responses to alpha-amino-3 hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), quisqualate and kainate but not NMDA. The synaptic response evoked by low frequency stimulation of Schaffer collateral-commissural fibres in 1 mM Mg2+-containing medium is completely blocked by this concentration of CNQX. In contrast the synaptic response evoked in Mg2+-free medium is not fully blocked by CNQX. The CNQX-insensitive component is, however, abolished by addition of a selective NMDA antagonist. The use of CNQX has allowed for the first time selective synaptic activation of NMDA receptors in the hippocampus. PMID- 2899310 TI - Effect of the 1-methyl-4-phenylpyridinium ion on phosphorylation of tyrosine hydroxylase in rat pheochromocytoma PC12h cells. AB - Effects of the 1-methyl-4-phenylpyridinium ion (MPP+) on DOPA formation and phosphorylation of tyrosine hydroxylase (TH) of rat pheochromocytoma PC12h cells were examined after the cells were cultured with MPP+. DOPA formed from endogenous tyrosine in PC12h cells after a 3-day culture with 100 microM MPP+ was decreased to less than 50% as compared to that in the control cells cultured without MPP+. Kinetical study showed that two apparent forms of TH with different Km existed in the cells cultured with 100 microM MPP+ but one form in that of control. Incorporation of radioactive phosphate into TH molecule was also reduced to 50% of its control value following a 3-day exposure to 100 microM MPP+. These results suggest that MPP+ acutely inhibits the phosphorylation of TH to decrease cellular DOPA formation. PMID- 2899309 TI - NMDA antagonists: lack of protective effect against hypoxic damage in CA1 region of hippocampal slices. AB - Rat hippocampal slices were exposed to a hypoxic insult in control medium or while exposed to the N-methyl-D-aspartate (NMDA) receptor antagonists DL-2-amino 7-phosphonoheptanoic acid (100 microM) or DL-2-amino-5-phosphonovaleric acid (25 or 100 microM). Synaptic transmission between Schaffer collaterals and CA 1 pyramidal cells was evaluated before and after the hypoxic period, and the DC potential in the CA 1 pyramidal cell layer was monitored during the hypoxic period. Neither antagonist significantly increased the proportion of slices in which synaptic transmission recovered following hypoxia, nor did they increase the latency of the spreading depression-like anoxic depolarization. We suggest that NMDA receptors are not involved in neural damage caused by severe hypoxia with sudden onset, while they may play a role in the effects of more moderate, gradual onset hypoxia and in post-ischemic reperfusion effects. PMID- 2899311 TI - Prognostic variables in treating vaginismus. AB - Twenty-three patients with vaginismus were seen in a Sexual Dysfunction Program over five years. Twenty of these patients continued in therapy and had successful outcomes. Length of therapy was analyzed and seen to be related to the following factors: duration of the dysfunction, and patient's conception of the etiology of the problem, history of previous attempts at operative treatment, motivational factors, the husband's degree of acceptance of the unconsummated marriage, previous organic abnormalities, extent of sexual knowledge, fear of sexually transmitted diseases, parental attitudes regarding sex, and the patient's attitude toward her genitalia. Follow-up of one to four years has revealed maintenance of sexual functioning in 95% of the couples. The three patients who dropped out and were considered failures all had had previous operative therapy and would not relinquish the idea that there was an anatomic abnormality causing their dysfunction. The method of therapy is reviewed. PMID- 2899312 TI - Effect of terfenadine on the response to exercise and cold air in asthma. AB - To assess the role of histamine as a mediator in the response to exercise and isocapnic hyperventilation of cold air (IHCA) in asthma, we studied nine asthmatic subjects, age 13 to 25 years. All had exercise induced asthma (EIA) and positive responses to IHCA. Baseline lung function was measured before standardized challenges with histamine, exercise and IHCA. On separate days, these tests were repeated 3 h after a single oral dose of 120 mg terfenadine (TF). Histamine responsiveness decreased significantly, with a provocative concentration, producing a greater than or equal to 20% fall in FEV1 (PC20), of 1.1 +/- 0.8 mg/ml (mean +/- SEM) before and 12.0 +/- 4.9 mg/ml after the antihistamine. EIA was significantly less after TF, with 53 +/- 5% mean maximal falls in FEV1 from baseline before, and 29 +/- 9% after treatment (P less than 0.01, paired t-test). In contrast, the effect of TF on the response to IHCA was insignificant, with mean maximal falls of 45 +/- 7% in FEV1 before, and 41 +/- 7% after treatment. There was a correlation between PC20 and lowest FEV1 (% predicted) for EIA (r = 0.56, P less than 0.05), but not for IHCA (r = 0.34, NS). This study indicates a role of histamine as a mediator in EIA but not in IHCA, supporting different mechanisms for both stimuli. PMID- 2899313 TI - Physiological assessment of growth hormone secretion in the diagnosis of children with short stature. AB - Many advances characterize the research into the diagnosis of short stature in children. Increasing evidence shows a continuous spectrum of growth hormone (GH) output among GH-deficient patients and short normal children. Although biosynthetic human GH could theoretically offer the chance of treating most slowly growing children, it is not certain that all short normal children with a poor height velocity could benefit from therapy. Indeed, besides auxological findings, the assessment of GH secretion remains essential in selecting candidates for therapy. In this respect the evaluation of GH secretion by means of tests that can explore the physiological pathways involved in the hormone output appears important. Moreover some clinical evidence suggests that pharmacological stimuli cause the pituitary release of stored GH perhaps unavailable in physiological conditions. Among the classical physiological tests, the exercise test, the standardization of which has been debated, is commonly used in clinical practice. The sleep test, i.e. the evaluation of sleep associated GH secretion, is the most important. It has no side effects and does not require the administration of exogenous stimuli. Several studies have demonstrated its reliability in diagnosing growth disorders in childhood, mainly if performed with EEG monitoring. Among the new physiological diagnostic approaches the most reliable test is the evaluation of 24-hour GH secretion. Knowledge of the integrated hormone concentrations appears particularly important in studying children who may have more subtle disturbances in GH secretion. These cases show normal GH response to provocative stimuli but show a reduced hormone output over 24 h. Indeed they respond well to human GH treatment. PMID- 2899314 TI - Regulation of growth hormone secretion. Relevance to the pediatrician. AB - The regulation of human growth hormone secretion is complex involving both a hypothalamic stimulating and inhibiting hormone. These neurohormones are further regulated by neurotransmitters. Abnormalities in growth hormone secretion may occur in neurologic, psychiatric and metabolic disorders not related to short stature. In addition, the diagnosis of deficiency states of growth hormone secretion can often be very difficult. Guidelines for the work-up of short children are given. PMID- 2899315 TI - [Effect of alpha- and beta-adrenoreceptor blockaders on thyroid function in rats of various ages]. AB - The effect of alpha-adrenoblocker dibenamine and beta-adrenoblocker propranolol on the blood level of thyroid hormones (TH) and TH production by isolated thyroids (T) was investigated in adult and old male rats. Isolated T were incubated for 4 h in medium 199 with or without TSH (100 mU/ml). TH blood concentration and specific TH production by isolated T was decreased with age. TSH stimulated thyroid hormone production in isolated T only in adult rats. Alpha or beta-adrenoblockers administration resulted in a decrease in the TH blood concentration, basal and TSH-stimulated thyroid hormone production in adult rats. The results obtained suggested that aging was accompanied by decreased adrenergic control of thyroid function. PMID- 2899316 TI - Discriminative and analgesic effects of mu and kappa opioids: in vivo pA2 analysis. AB - This paper illustrates the use of antagonists to study receptor mediation of the discriminative stimulus effects of opioids and to determine if their analgesic effects are mediated in a similar manner. Analysis by pA2 was used to quantify interactions between the opioid antagonist quadazocine and several opioid agonists. Interactions were examined under a drug discrimination procedure and under a tail withdrawal analgesia procedure. Values of pA2 for quadazocine in combination with the kappa agonists bremazocine, ethylketazocine, and U50,488 ranged between 6.1 and 6.4 under the drug discrimination and tail withdrawal procedures. In contrast, the pA2 values for the mu agonists etorphine, fentanyl, and morphine under these procedures ranged between 7.6 and 8.2. The difference between these pA2 values indicates that the affinity of quadazocine for the receptors mediating the effects of the kappa agonists is over one log unit lower than its affinity for the receptors mediating the effects of the mu agonists. This suggests that the discriminative stimulus and analgesic effects of kappa opioid agonists are mediated at the same opioid receptor type, which is different from the type of opioid receptor at which mu agonists produce their discriminative stimulus and analgesic effects. PMID- 2899317 TI - Receptor mediation of the discriminative stimulus properties of phencyclidine and sigma-opioid agonists. AB - Evidence has accumulated that the discriminative stimulus effects of phencyclidine (PCP) may be transduced by a specific receptor in mammalian brain. Two major lines of evidence support this hypothesis. One is the structure activity correlation that arylcyclohexylamine analogs of PCP have for PCP-like discriminative effects and displacement of [3H]PCP binding. The other, even stronger, evidence is that representatives of some nonarylcyclohexylamine classes of drugs are both generalized from PCP and have activity at PCP-binding sites. These include the psychotomimetic sigma-agonist opioids such as (+)-N allylnormetazocine (NANM), the 1,3-substituted dioxolanes dexoxadrol and etoxadrol and some benz(f)isoquinolines. Early evidence suggested that there may be a complete overlap in the discriminative effects and receptor systems for PCP and sigma-agonists, and there continues to be evidence to support the commonality of these drug groups. On the other hand, binding studies with radiolabeled sigma agonists have revealed a non-PCP site. The role of this site in the behavioral actions of sigma-agonists is at present unknown. PCP analogs and other PCP-like drugs also can function as reinforcers for self-administration behavior, suggesting that the same cellular mechanisms may be responsible for both discriminative and reinforcing stimulus effects of these drugs. PCP has been shown to block many of the in vitro and in vivo effects of N-methyl-D-aspartate (NMDA), a putative specific agonist for a subtype of excitatory amino acid receptor. Recent evidence that NMDA antagonists are generalized from PCP in rats and pigeons provides evidence that modification of excitatory amino neurotransmission may be a physiological function of the PCP receptor and that this receptor complex may be involved in PCP's discriminative stimulus effects. PMID- 2899318 TI - Central nervous system stimulants: neuropharmacological mechanisms. AB - The mechanisms underlying CNS-stimulant drug discrimination are discussed. Although different doses of CNS stimulants may produce qualitatively different cues, it appears that a relatively low dose of d-amphetamine (e.g., 1 mg/kg) elicits a "general" CNS-stimulant cue. Presynaptically, this cue may primarily depend on release of endogenous dopamine whereas inhibition of dopamine reuptake, per se, is insufficient to elicit the cue. Postsynaptically, the involvement of both dopamine D-1 and D-2 receptors is implicated. Furthermore, in the drug discrimination situation, D-1/D-2 receptors may be coupled differently than in dopamine-dependent locomotor activation. Anatomically, CNS-stimulant drug discrimination may depend primarily on mesolimbic dopamine systems. PMID- 2899319 TI - Discriminative stimulus properties of anxiolytic and sedative drugs: pharmacological specificity. AB - In the first set of experiments rats were trained to discriminate a dose of 5 mg/kg chlordiazepoxide from saline. The chlordiazepoxide cue was antagonized by flumazepil (Ro 15-1788) and by CGS 8216, and generalized to a variety of anxiolytic and sedative drugs including the benzodiazepine receptor ligands zopiclone, suriclone, CL 218,872, CGS 9896, and ZK 91296. The novel imidazopyridine hypnotic, zolpidem, which also displaces benzodiazepines from their binding sites, failed to produce high levels of responding on the chlordiazepoxide-associated level except at a dose which greatly reduced rates of lever pressing. In further experiments rats were trained to discriminate a dose of 2 mg/kg zolpidem from saline. This dose produced reductions in response rates but an attempt to establish a lower dose of zolpidem as a discriminative stimulus was largely unsuccessful. Zolpidem-appropriate responding was produced by pentobarbital, chlordiazepoxide, triazolam, CL 218,872, clorazepate, lorazepam, quazepam, and zopiclone but only at doses which reduced response rates. The zolpidem cue was antagonized by flumazepil, CGS 9896, and ZK 91296. While the discriminative stimulus produced by chlordiazepoxide may be related to its anxiolytic action, the zolpidem stimulus is probably more closely associated with sedation. It was also tentatively concluded that the stimulus properties of chlordiazepoxide and zolpidem are produced by activity at different subtypes of benzodiazepine receptors. PMID- 2899320 TI - Comparison of discriminative stimuli produced by full and partial benzodiazepine agonists: pharmacological specificity. AB - Benzodiazepines produce discriminative stimuli that are stereospecific and antagonized by specific benzodiazepine receptor antagonists. The potency of these stimuli correlate with the ability of these compounds to bind to the benzodiazepine receptor complex. These data indicate that benzodiazepine stimuli are transduced via the benzodiazepine receptor. The underlying basis of these stimuli is unclear. Results with novel compounds that produce preclinical anxiolytic effects without the sedation and muscle relaxation of the classical benzodiazepines suggest that muscle relaxation may contribute to these stimuli. A direct comparison of discriminative stimuli established on a classical benzodiazepine agonist with the stimuli established on a partial benzodiazepine agonist supports the possibility that the classical benzodiazepine cue is mediated by a muscle relaxant effect, while the partial agonist cue is related to the anxioselectivity of the compound. PMID- 2899321 TI - Down-regulation of beta-adrenergic receptors: agonist-induced reduction in receptor mRNA levels. AB - Incubation of DDT1 MF-2 hamster vas deferens cells with beta-adrenergic agonists results in a time- and concentration-dependent decreases in both beta-adrenergic receptor (beta AR) responsiveness and receptor number. Receptor mRNA levels were quantified by DNA-excess solution hybridization by using a 170-nucleotide single stranded probe derived from the hamster beta 2AR cDNA. RNA blot analysis of poly(A)+-selected RNA with the solution probe revealed a 2.2-kilobase species. Digestion of the RNA/solution probe mixture with S1 endonuclease revealed a single species of RNA (170 bases) that was protected by the solution probe. DDT1 MF-2 cells were found to contain 0.38 pg of beta AR mRNA per microgram of total cellular RNA. Incubation (16 hr) with isoproterenol decreased beta AR mRNA levels in cells by 40%. This agonist-induced decrease in receptor mRNA levels was found to be dependent on the time of incubation and the dose of agonist. The decrease in beta AR mRNA was half-maximal at 0.1-0.5 microM isoproterenol. The beta adrenergic antagonists CGP 20712A (beta 1-selective) and ICI 118,551 (beta 2 selective) blocked in a dose-dependent fashion the ability of isoproterenol to effect receptor mRNA levels. The beta 2-adrenergic antagonist displayed a potency 25-fold greater than that of the beta 1-adrenergic antagonist, in agreement with the subtype of receptor (beta 2) expressed by these cells. For down-regulated cells in which receptor mRNA levels declined in response to agonist, the addition of the antagonist ligand (-)-propranolol (1 microM) was able to restore receptor mRNA levels to 90% of the control value within 12 hr. Full recovery of steady state beta AR mRNA was achieved within 60 hr. These studies provide a molecular explanation for the down-regulation of GTP-binding regulatory protein (G protein) linked cell-surface receptors that accompanies desensitization. PMID- 2899322 TI - Isolation of a cDNA clone encoding a biologically active thyroid hormone receptor. AB - We have isolated a c-erbA cDNA clone from a GH3 cell library. The clone, denoted erb62, is 4.5 kilobases long and encodes a 461-amino acid beta-type c-erbA protein. This c-erbA protein binds 3,5,3'-triiodothyronine (T3) and T3 analogs with affinities similar to those of the authentic T3 receptor. By RNA gel blot analysis, erb62 hybridizes to a 6-kilobase RNA found in organs that express T3 receptors--e.g., heart, kidney, and brain. A COS-cell transient cotransfection system was used to show that erb62 encodes a biologically active T3 receptor. An oligonucleotide, corresponding to a portion of the rat growth hormone gene 5' flanking region that contains a T3 response element, was inserted on the 5' side of the herpes simplex virus thymidine kinase promoter in a chloramphenicol acetyltransferase-expressing plasmid. Reporter gene expression directed by this hybrid promoter was T3 inducible only if this plasmid was cotransfected with an erb62-expressing plasmid. PMID- 2899323 TI - Amplified expression of the HER2/ERBB2 oncogene induces resistance to tumor necrosis factor alpha in NIH 3T3 cells. AB - Functional characterization of oncogene products that induce cellular transformation has progressed rapidly in recent years. However, less is known about the mechanism(s) by which the transformed cells may escape destruction by host immune defenses and form tumors. A recently described oncogene that has an important association with aggressive human breast carcinoma is "HER2," for human epidermal growth factor receptor 2. The oncogene has also been called NGL and human c-erbB-2 (ERBB2). In this paper we show that amplification of HER2 oncogene expression can induce resistance of NIH 3T3 cells to the cytotoxic effects of recombinant tumor necrosis factor alpha (rTNF-alpha) or macrophages. Resistance is accompanied by an increased dissociation constant for rTNF-alpha binding to high-affinity receptors on the HER2-transformed NIH 3T3 cells. The resistance phenotype is independent of transformation since NIH 3T3 cells transformed by the activated human homologue of the Harvey-ras oncogene (HRAS) retain high-affinity binding sites for rTNF-alpha as well as sensitivity to its cytotoxic effects. These results suggest that HER2 may potentiate tumorigenesis by inducing tumor cell resistance to host defense mechanisms. PMID- 2899324 TI - Molecular evidence for somatic recombination in the ribosomal DNA of Tetrahymena thermophila. AB - The ribosomal DNA (rDNA) in Tetrahymena thermophila is a 21-kilobase-pair palindromic DNA molecule that replicates autonomously in the macronucleus and is maintained at the level of about 10,000 copies per macronucleus. The rDNA of inbred strain C3 outreplicates the rDNA of inbred strain B in most B/C3 heterozygous macronuclei, generating macronuclei containing exclusively C3 rDNA sequences. In 1% or less of the B/C3 heterozygous macronuclei, however, rDNA sequences derived from both B and C3 strains persist in the macronucleus (co maintainers). We report here that long-term culture of co-maintainers has yielded recombinant rDNA molecules combining sequences from both parental inbred strains. The genetic structure of such molecules also gives us virtual certainty that the differential replication of C3 rDNA with respect to B rDNA is due to the DNA sequence difference previously reported in domain 2 of the rDNA replication regions of the two strains. PMID- 2899325 TI - Two mutant alleles of the human cytochrome P-450db1 gene (P450C2D1) associated with genetically deficient metabolism of debrisoquine and other drugs. AB - The "debrisoquine polymorphism" is a clinically important genetic defect of drug metabolism affecting 5-10% of individuals in Caucasian populations. It is inherited as an autosomal recessive trait. A full-length cDNA for human cytochrome P-450db1, the deficient enzyme (also designated P450IID1 for P450 family II subfamily D isozyme 1), has recently been cloned. Leukocyte DNA from "extensive metabolizers" (EMs) or "poor metabolizers" (PMs) of debrisoquine was examined by Southern analysis. Two polymorphic restriction fragments were associated with the PM phenotype when DNAs from 24 unrelated PM and 29 unrelated EM individuals were probed with P-450db1 cDNA after digestion with Xba I restriction endonuclease and Southern blotting: a polymorphic 44-kilobase (kb) fragment was found in 58% of PMs but only in 3.4% of EMs, and a polymorphic 11.5 kb fragment was present in 33% of PMs but in none of the EMs. Seventy-five percent of PMs had either the 44-kb or the 11.5-kb fragment or both. Segregation of these restriction fragment length polymorphisms in the families of six PM probands demonstrated that each of the two fragments is allelic with the 29-kb fragment present in all EM individuals and suggests that they identify two independent mutated allels of the P-450db1 gene (designated P450C2D1). At least a third mutated allele not detected by these restriction fragment length polymorphisms must be present in the population. The Xba I 44-kb fragment and 11.5-kb fragment were in linkage disequilibrium with restriction fragment length polymorphisms generated by four and five additional restriction endonucleases, respectively, which can be used to identify the same mutant alleles for the P 450db1 gene. PMID- 2899326 TI - Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. AB - The effect of various drugs on the extracellular concentration of dopamine in two terminal dopaminergic areas, the nucleus accumbens septi (a limbic area) and the dorsal caudate nucleus (a subcortical motor area), was studied in freely moving rats by using brain dialysis. Drugs abused by humans (e.g., opiates, ethanol, nicotine, amphetamine, and cocaine) increased extracellular dopamine concentrations in both areas, but especially in the accumbens, and elicited hypermotility at low doses. On the other hand, drugs with aversive properties (e.g., agonists of kappa opioid receptors, U-50,488, tifluadom, and bremazocine) reduced dopamine release in the accumbens and in the caudate and elicited hypomotility. Haloperidol, a neuroleptic drug, increased extracellular dopamine concentrations, but this effect was not preferential for the accumbens and was associated with hypomotility and sedation. Drugs not abused by humans [e.g., imipramine (an antidepressant), atropine (an antimuscarinic drug), and diphenhydramine (an antihistamine)] failed to modify synaptic dopamine concentrations. These results provide biochemical evidence for the hypothesis that stimulation of dopamine transmission in the limbic system might be a fundamental property of drugs that are abused. PMID- 2899328 TI - Benzodiazepine abuse in patients of doctors in domiciliary practice in the Basle area. AB - In the city of Basle with a catchment area of 300,000 inhabitants a significant number of physicians were asked for observations concerning benzodiazepine abuse by their patients. In 1985, 31 patients abusing benzodiazepine only were observed, which represents an incidence of 1:10,000 or 0.01%. In addition, concrete information on 88 patients with multiple abuse was obtained. Demographic data, diagnosis and main reason of abuse, data on most frequently abused drugs, consequences of abuse, as well as measures against the abused are described in relation to the two main groups of abusers. PMID- 2899327 TI - L-glutamate-induced depolarization in solitary photoreceptors: a process that may contribute to the interaction between photoreceptors in situ. AB - L-Glutamate is a leading candidate for the vertebrate photoreceptor transmitter. In addition to the signal transmission to second-order neurons, photoreceptors communicate with each other not only electrically but also chemically. In the present study, by using solitary turtle photoreceptors, we examined the possibility that L-glutamate mediates interreceptor communication. L-Glutamate evoked an inward current in all subtypes of photoreceptors voltage-clamped to the resting potential. The highest glutamate sensitivity was located at the axon terminal. Both stereoisomers of aspartate were effective, whereas kainate, quisqualate, N-methyl-D-aspartate, and D-glutamate were ineffective. The presence of Na+ was essential to response generation; even Li+ could not substitute for Na+. The relation between L-glutamate-induced current and the membrane voltage was strongly inward-rectifying. These results favor the hypothesis that the L glutamate-induced response is generated by an electrogenic uptake carrier. However, L-glutamate-induced current was always accompanied by an increase in current fluctuations, a phenomenon commonly observed in ion channels but not expected for an uptake carrier. Although the underlying mechanism needs further elucidation, it seems likely that L-glutamate is a transmitter for communication between photoreceptors. PMID- 2899329 TI - Antidepressant combination therapy of endogenous depressions with benzodiazepines or neuroleptics--a study comparing adjuvant treatment with oxazolam versus chlorprothixene. AB - Antidepressants are routinely administered in combination with benzodiazepine tranquilizers or low-potency neuroleptics. A controlled study was conducted involving 40 endogenous depressive inpatients who were treated with maprotiline in combination with the benzodiazepine oxazolam or the neuroleptic chlorprothixene. After a period of two weeks there was no significant difference in the clinical ratings (HRSD, Bf-S, BL, CGI) of the two groups studied. Only in the factor "anxiety" and the adjective mood scale scores was there a tendency toward quicker onset of action (third day) in the patient group treated with oxazolam, though it was not statistically significant. The clinical global evaluation (efficacy, tolerability) showed more favorable ratings for oxazolam than for chlorprothixene. Both substances were generally tolerated well; oxazolam hardly ever caused any side effects. However, a slight deterioration of some patients' conditions was observed after discontinuation of oxazolam. PMID- 2899330 TI - High-dose infusion therapy for severe depressions. AB - The present paper reports the results of high-dose intravenous antidepressive treatment performed at the Psychiatric Department of the Hungarian Central Hospital in Budapest. Based on the differences in the comparative dexamethasone suppression tests (DSTs), prolactin (PRL) responses and Fischer Symptom Check List (FSCL) scores, it is hypothesized that a high parenterally administered dose of dibenzepine acts differently in comparison to oral drugs, which are extensively metabolized in the hepatic microsomal system. The results obtained so far suggest that the effect of high-dose intravenous dibenzepine in endogenous depressive states is comparable to that of electroconvulsive therapy (ECT), as far as the regression of symptoms and biochemical changes are concerned. PMID- 2899331 TI - Positron emission tomography and subcortical glucose metabolism in schizophrenia. AB - Our previous observation of a disturbed subcortical-to-cortical gradient of activity in schizophrenia was further elucidated by examining glucose metabolism in three subcortical structures: lenticular nucleus, caudate nucleus, and thalamus. Local cerebral glucose metabolism was determined with 18F fluorodeoxyglucose using positron emission tomography (PET) in a sample of 20 unmedicated schizophrenics and 18 normal volunteers. Repeated evaluations were performed for 12 schizophrenics following treatment with psychotropic medications and for 11 controls. Unmedicated schizophrenics had lower cortical and caudate absolute metabolic rates. Subcortical-to-cortical ratios for the lenticular nucleus and thalamus were increased in schizophrenics compared with controls, reflecting a preservation of activity in these structures relative to decreased cortical metabolism. When patients were grouped by length of medication-free period before the initial study, there was a trend for patients who had been medication free less than 6 months to have higher subcortical ratios. However, there were no consistent effects of medication in the subsample of patients whose PET studies were repeated following treatment. The results demonstrate relative hypermetabolism in structures implicated in dopamine pathways. An understanding of the physiological significance of this finding awaits the combined measurement of metabolic activity and neuroreceptors in schizophrenics. PMID- 2899332 TI - Neuroleptic effects on electrodermal responsivity to soft tones and loud noise in schizophrenia. AB - Electrodermal procedures have consistently yielded two groups of schizophrenic patients--responders and nonresponders--on the basis of their electrodermal responsivity to auditory stimuli. The reliability of this finding has proved to be a cornerstone of autonomic research in schizophrenia. Previous investigators have reported that neuroleptic medications have little or no effect on electrodermal responsivity to mild tones. The current research found that patients receiving neuroleptics with high anticholinergic properties showed significantly less electrodermal responsivity compared with those receiving low anticholinergic neuroleptics. This was true for both loud and mild auditory stimuli. PMID- 2899333 TI - Central mu, delta- and kappa-opioid influences on intestinal water and electrolyte transport in dogs. AB - The effects of intracerebroventricular (i.c.v.) administration of opioid peptides with mu-(DAGO), mu- and delta-(DALAMIDE, DADLE) and kappa-(dynorphin) properties on normal and stimulated (cholera toxin) net fluxes of water, Na+ and K+ through a jejunal Thiry-Vella loop were investigated in conscious dogs. Basal net water absorption was slightly, but significantly (P less than 0.05) increased during i.c.v. infusion of DALAMIDE or DAGO (0.5 ng/kg/min) but not DADLE and dynorphin (1-13) at the same rate; DALAMIDE and DAGO also markedly reduced (by 72.3 and 79.5% respectively) the secretory effects of cholera toxin (0.4 micrograms/ml). Similar effects were obtained with DALAMIDE and DAGO when injected i.c.v. as a bolus (100 ng/kg) prior to cholera toxin infusion; they were suppressed after i.v. pretreatment with naltrexone (0.3 mg/kg) but also with propranolol (0.2 mg/kg). In contrast, i.v. phentolamine (0.2 mg/kg) and bilateral truncal vagotomy, were unable to block their effects. These results suggest that Met enkephalin can act centrally to affect intestinal transport of (i) water and (ii) electrolytes in dogs. They act probably at central mu-receptors which are involved in the regulation of intestinal secretion mediated through a central or peripheral beta-adrenergic pathway. PMID- 2899334 TI - Effect of vagotomy and atropine on plasma somatostatin response to a meal in conscious dogs. AB - In 4 conscious dogs with gastric fistulas the somatostatin responses to a meal were measured and compared to the responses seen after i.v. infusion of atropine sulfate (20 and 50 micrograms.kg-1.h-1) or cimetidine (8 mg.kg-1.h-1). The experiments were repeated after truncal vagotomy. The somatostatin responses to bombesin (0.5 micrograms.kg-1.h-1) were also measured before and after vagotomy. Vagotomy decreased basal and postprandial somatostatin levels and reduced the somatostatin responses to feeding during the first 30-min period following the ingestion of the meal but not during subsequent periods. Bombesin-induced somatostatin release was increased after vagotomy. Atropine decreased the somatostatin responses to the meal before and after vagotomy. Cimetidine had no significant effect. These studies suggest that, in conscious dogs, somatostatin released into the circulation is partly under vagal control and that, as for gastrin release, vagal pathways for stimulation and inhibition are present. Our studies also suggest that cholinergic mechanisms are involved in the control of postprandial somatostatin release. PMID- 2899335 TI - [Pharmacologic effect of a new synthetic analog of somatostatin (SMS 201-995) on fasting intragastric pH in subjects with duodenal ulcer]. PMID- 2899336 TI - Enhancing effect of bucolome on biliary excretion of ouabain and digoxin in the rat. AB - The effect of bucolome (1-cyclohexyl-5-n-butyl-2,4,6-trioxoperhydropyrimidine) on the biliary excretion of intravenously administered ouabain and digoxin was examined in rats. The intravenously administered [3H] ouabain (0.1 mg/100 g b wt) was more rapidly excreted in the bile in female rats than in males. Intraperitoneal administration of bucolome induced a two fold increase in bile flow rate, accompanied by a significant increase in biliary recovery of ouabain during first 10 min (by 100% in males and 50% in females) resulting in significantly higher 60-min total biliary recoveries in both sexes. In female rats 80% of radioactivity was recovered in the bile as an unmetabolized form after 10 min of intravenous administration of [3H] digoxin. Biliary excretion of the parent drug, digoxin, was also enhanced by intraperitoneal administration of bucolome. Although the underlying mechanism(s) remains unknown, it was shown that biliary excretion of both ouabain and digoxin was enhanced by bucolome, as was previously shown for ouabain in male rats. PMID- 2899337 TI - Methylmercury-cysteinylglycine constitutes the main form of methylmercury in rat bile. AB - The chemical form of methylmercury (MM) in bile was studied by gel filtration and ion exchange chromatography using male rats of various ages. EDTA was added to all mixtures used throughout the experimental procedures in order to prevent oxidation of non-protein sulfhydryl compounds (NPSHs). MM-cysteinylglycine (CysGly) was found to be a predominant chemical form of MM in bile of 4 to 22 week-old rat exposed to methylmercuric chloride. The ratio of MM-glutathione (GSH) tended to increase with age after 4 weeks until 12 weeks of age, reflecting the age-dependent increase in the ratio of GSH to total NPSHs in bile. In 8-week old rats, although the biliary concentration of GSH was about three times higher than that of CysGly, MM-CysGly was still one of the main chemical forms of MM in bile. This suggests that CysGly has a higher affinity for MM than GSH. In fact, when MM was mixed in vitro with GSH and CysGly in the same molar ratio as that in the bile of 8-week-old rat, MM-CysGly was found to be a predominant mercury-thiol complex. Thus, age-dependent changes in the molar ratio of biliary NPSHs together with their affinity to MM seems to determine the biliary chemical form of MM administered or added into the bile in vitro. PMID- 2899338 TI - New method for easy labeling of beta-2-agonists in the metered dose inhaler with technetium 99m. AB - The actual deposition pattern of micronized drugs from metered dose inhalers (MDI) is incompletely known because there are no methods available to label the drugs (beta 2-agonists) with gamma-emitters. Indirect measurements of the distribution of the drug in man differed greatly due to the method used. Our method uses the better solubility of 99mTcO4- in the beta 2-agonist-micronized drug in relation to the propellant with surfactant. The principle is to extract the 99mTcO4- from the original water phase into the liquid phase of the propellant with ethyl methyl ketone. For labeling the micronized drug particles, the original MDI must be cooled to -60 degrees C and some labeled propellant (including surfactant) with high specific activity of 99mTcO4- is added through an aperture in the bottom of the container. The aperture is sealed with a screw. After rewarming the MDI, more than 90% of the added 99mTcO4- is dissolved in the beta 2-agonist-micronized drug in relation to its volume. This is proved by comparing the distribution of the radioactivity component with chemical analysis. The pattern of deposition of both MDIs - placebo and beta 2-agonist-micronized drug - was shown to be similar in healthy volunteers. With a labeled MDI a preliminary study with 2 different inhaling maneuvers was performed in 7 volunteers: inhaling from residual volume after a pause of 2 s the intrabronchial deposition was 18.7%, and inhaling at 50% of vital capacity maneuver the intrabronchial deposition was 33.0%. The data obtained with actual measurement of the inhaled drug from MDI suggest greater intrabronchial deposition than was assumed before in the literature. PMID- 2899339 TI - [Takayasu's arteritis: study of 11 cases]. PMID- 2899340 TI - [Bioequivalency of salazosulfapyridine tablets]. PMID- 2899341 TI - [Pharmaceutical characteristics of depot neuroleptics. Their use and efficacy in the psychiatric clinic]. PMID- 2899342 TI - [Hematology: biomedical discipline and interdiscipline constantly updated]. PMID- 2899343 TI - [Importance of immunoserological research in the diagnosis and follow-up of the evolution of autoimmune hemolytic anemias]. PMID- 2899345 TI - [Blast study in acute leukemia using monoclonal antibodies]. PMID- 2899344 TI - [Acute promyelocytic leukemia. A study of 119 cases and a review of the literature]. PMID- 2899346 TI - [The staging of chronic lymphatic leukemia. Its prognostic value and therapeutic implications]. PMID- 2899347 TI - [Treatment by the CHOP protocol in malignant non-Hodgkin lymphomas with high malignancy]. PMID- 2899348 TI - [Malignant non-Hodgkin's lymphomas. The working morphological classification of the Hematology Clinic]. PMID- 2899349 TI - [The value of an in vitro method of granulomonocytic colonies for the diagnosis and prognosis of myelodysplastic syndromes]. PMID- 2899350 TI - [Erythrocytic fragmentation--a sign of disseminated intravascular coagulation]. PMID- 2899351 TI - [Hemorrhagic thrombocythemia: a clinical study of 30 cases and a review of the literature]. PMID- 2899352 TI - [Pathogenetic mechanism of the DIC syndrome]. PMID- 2899353 TI - [Chronic refractory anemia with manifestations of nocturnal paroxysmal hemoglobinuria and chronic disseminated coagulopathy preceding the onset of acute myelomonocytic leukemia]. PMID- 2899354 TI - Activation of human T cells by neuraminidase-galactose oxidase-treated erythrocytes involving CD2 (T11) and its complementary structure. AB - Human T lymphocyte proliferation induced by neuraminidase-galactose oxidase (NAGO)-treated autologous erythrocytes (HENAGO) plus polyethylene glycol (PEG) has previously been shown to be independent of accessory cells. Here, we show that the response to HENAGO + PEG was accompanied by interleukin 2 (IL-2) release and was inhibited by anti-IL-2 and anti-IL-2 receptor antibodies. HENAGO alone initiated DNA synthesis together with phorbol ester (12-O-tetradecanoyl-phorbol 13-acetate; TPA). To elucidate the nature of the stimulatory signals NAGO-treated sheep erythrocytes (SENAGO) were used in additional experiments. In parallel to the superior rosetting capacity of SE compared to HE. SENAGO were by themselves stimulatory, and the response was further enhanced by PEG or TPA. Antibody L180/1, specific for the T11 (CD2) target structure (T11TS) on SE, homologous to the human CD2 ligand LFA-3, abolished the response to SENAGO alone or when combined with PEG or TPA. The results suggest that ENAGO induce T-cell response through CD2-LFA-3-T11TS interaction, and via other surface antigens bound by the oxidatively induced aldehyde groups on ENAGO. PMID- 2899355 TI - [Advances in research on sleep mechanisms]. PMID- 2899356 TI - Carboxyl terminal domain of Gs alpha specifies coupling of receptors to stimulation of adenylyl cyclase. AB - The alpha subunits of Gs and Gi link different sets of hormone receptors to stimulation and inhibition, respectively, of adenylyl cyclase. A chimeric alpha i/alpha s cDNA was constructed that encodes a polypeptide composed of the amino terminal 60% of an alpha i chain and the carboxyl terminal 40% of alpha s. The cDNA was introduced via a retroviral vector into S49 cyc- cells, which lack endogenous alpha s. Although less than half of the hybrid alpha chain is derived from alpha s, its ability to mediate beta-adrenoceptor stimulation of adenylyl cyclase matched that of the normal alpha s polypeptide expressed from the same retroviral vector in cyc- cells. This result indicates that carboxyl terminal amino acid sequences of alpha s contain the structural features that are required for specificity of interactions with the effector enzyme, adenylyl cyclase, as well as with the hormone receptor. PMID- 2899357 TI - Sphenopalatine ganglion blocks for the treatment of nicotine addiction. AB - The purpose of this study was to investigate the effects of sphenopalatine ganglion block upon the physical symptoms of nicotine withdrawal in a double blind placebo-controlled study. Seventeen patients completed a course of treatment which involved daily intranasal application of local anesthetic (bupivacaine or cocaine) or saline over the sphenopalatine ganglion. The reported numbers of daily symptoms of physical discomfort were recorded during the preprocedure period. Analysis of variance results indicated that patients in all three groups experienced a significant decline in the number of symptoms of physical discomfort over the six-day withdrawal period. Further findings provided evidence of significantly fewer symptoms of discomfort for patients in the anesthetic treatment groups than in the placebo control group, though no statistically significant difference emerged between the two anesthetic treatment groups. Accelerated alleviation of discomfort during nicotine withdrawal may increase the success of smoking cessation. PMID- 2899359 TI - The International Working Party for the Diagnosis and Treatment of Carcinoma of the Cervix. PMID- 2899358 TI - Neuroleptic malignant syndrome: guidelines for treatment and reinstitution of neuroleptics. AB - The neuroleptic malignant syndrome (NMS) is a dangerous, often fatal, idiosyncratic disorder presumably of the basal ganglia and hypothalamus. It is usually associated with neuroleptic medications, and it is believed to be related to blockage of dopamine receptors in the brain. The NMS has also been reported in patients with Parkinson's disease after withdrawal of antiparkinsonian agents during "drug holidays." Cardinal features include fever, muscular rigidity, an elevated serum level of creatine phosphokinase, changes in mental status, and autonomic dysfunction. Although treatment has been largely supportive, dopamine agonists, such as bromocriptine, and a direct-acting muscle relaxant, dantrolene, have been used with good clinical outcome. Guidelines for reinstitution of neuroleptics are suggested. PMID- 2899360 TI - [The basic therapy of rheumatoid arthritis]. PMID- 2899361 TI - Cryptorchidism, and epidemiologic study with emphasis on the relationship to central nervous system dysfunction. AB - This case-control study examines the relation of cryptorchidism to central nervous system dysfunction. Elevated odd ratios were found for cerebral palsy (RR = 34), low IQ (RR = 2.7), and low motor function measured by the Bayley test (RR = 3.6). Low IQ and cerebral palsy were independent risk factors for cryptorchidism. Breech labor (RR = 2.6), a gestation less than 34 weeks (RR = 2.0), and being a twin (RR = 4.1) were also independent risks. Other risk factors were estrogen use by the mother (RR = 3.3) and a maternal Quetelet index less than 24 (RR = 1.6). All of these risks were statistically significant. These factors suggest that cryptorchidism may be caused either by sex steroid action directly on the testes or by CNS damage, which in turn causes suppression of pituitary gonadotropins. The increased occurrence of cryptorchidism in twins and small babies indicates that retarded general fetal development can be another mechanism for maldescent of the testes. PMID- 2899362 TI - Immunosuppression of graft rejection with idarubicin-monoclonal antibody conjugates by elimination of T cell subsets in vivo. AB - Idarubicin, a more therapeutically effective derivative of daunomycin, when coupled to monoclonal antibodies that react with murine and human tumors has the ability to specifically target and eradicate tumor cell populations in vitro and in vivo. In this study the in vitro and in vivo efficacy of idarubicin coupled to monoclonal antibodies reactive with distinct subpopulations of lymphocytes (L3T4+, Ly-2+) has been characterized. Using a tumor allograft model in vivo the potential use of drug-monoclonal antibody conjugates to prevent graft rejection has been investigated. Three to five molecules of Idarubicin could be coupled to the monoclonal antibodies (anti-Ly-2.1, anti-L3T4, or anti-Thy-1) with retention of protein solubility and antibody activity. Some loss of idarubicin activity (4 10-fold) occurred upon conjugation to the monoclonal antibodies--however, selective cytotoxicity for antibody reactive cell lines was observed. All three conjugates demonstrated the capacity to significantly deplete reactive subsets of spleen cells--further evidenced by the ability of combined idarubicin-anti-L3T4 and Idarubicin-anti-Ly-2.1 treatment of idarubicin-anti-Thy-1 treatment to prolong the survival of (Ly-2-, L3T4-) P388D1 tumor grafts in CBA mice in the presence of H-2 and non H-2 antigenic differences. This form of selective immunosuppression may have relevance for the treatment of graft rejection in man. PMID- 2899363 TI - An anti-human-T-cell monoclonal antibody with specificity for a novel determinant. AB - A new antihuman T cell monoclonal antibody, MAb 22, recognizes an antigen that is present on all mature T cells, but detected on only a subset of thymocytes. Dual color flow microfluorimetry (FMF) demonstrates that MAb 22 staining has concordant distribution with pan-T MAb specific for CD3 and CD5 and includes the CD4 and CD8 subsets; other FMF studies confirm T cell specificity of MAb 22 expression by cells of hematopoietic origin. The antigen recognized by MAb 22 is expressed on only a subset of thymocytes and by dual FMF is expressed at a mature thymocyte stage. Immunoprecipitation by MAb 22 demonstrates a series of molecules with a predominant 45 KD protein and associated 12 and 95 KD proteins under reducing conditions, while a 92 KD protein predominates under nonreducing conditions. Comparisons of expression on a variety of T cell lines, including a mutant line defective in the expression of the T cell receptor, by FMF analysis further distinguishes the determinant recognized by MAb 22 from those detected by MAb of defined T cell specificity. PMID- 2899364 TI - Study of murine T cell migration using the Thy-1 allotypic marker. Demonstration of antigen-specific homing to lymph node germinal centers. AB - We describe the use of Thy-1 alloantigen as a marker for in vivo T lymphocyte homing studies. Following transfer of 5 x 10(7) peripheral node T cells i.v., 32% of the transferred cells could be recovered in the host lymphoid organs (spleen, lymph nodes, Peyer's patches, and thymus); 11% of the T cells in the lymph nodes were donor derived. The transferred T cells assume the same microenvironmental and immunophenotypic distribution as the host T cells. The transferred T cells are identifiable in peripheral lymph nodes up to 170 days posttransfer, gradually declining in number during this time without evidence of rejection. This Thy-1 transfer technique permits T lymphocyte homing studies to be performed under physiologic conditions without problems of loss of lymphocyte subsets, selective labeling of lymphocyte populations, or long-term marker loss or dilution. We then employ this technique to demonstrate the antigen-directed homing of peripheral T cells to lymph node germinal centers. PMID- 2899365 TI - Medical management of ulcerative colitis and indications for colectomy. PMID- 2899366 TI - Medical management: its accomplishments in Crohn's disease and indications for surgery. PMID- 2899367 TI - [The occurrence of antibiotic-resistant Aeromonas and Vibrio species in river water]. AB - 262 samples of river water had been analysed for the occurrence of antibiotic resistant Aeromonas and Vibrio strains. The bacteria were cultured on selective media containing the antimicrobial chemotherapeutic agents oxytetracycline, chloramphenicol, streptomycin, ampicillin, kanamycin, gentamycin or trimethoprim. Although it was not possible to identify antibiotic resistant bacteria of the genus Vibrio, resistant strains of Aeromonas hydrophila with a wide variety of resistance patterns could be cultured in many cases. R plasmids were found by means of conjugation in 21.2% of the 826 tested Aeromonas hydrophila strains. They were characterized with the aid of the fin- and pili test. The majority of the R plasmids were fin-negative, and the sex pili could be assigned strikingly often to sex pilus group C with the phages we used. 15 strains of Aeromonas hydrophila had been tested in agarose gel electrophoresis on plasmid DNA. In 11 Aeromonas hydrophila strains with transferable and in 3 from 4 strains with non transferable multiple antibiotic resistance plasmid DNA with 100 Megadalton had been found. PMID- 2899368 TI - Glucagon and glucose tolerance in liver cirrhosis. AB - The present study was undertaken in order to establish the significance of glucagon in glucose intolerance in liver cirrhosis. The plasma glucose response to an oral glucose load (75 g) was determined in 10 control subjects and in 10 cirrhotic patients, after infusions of: glucagon (3 ng.kg-1.min-1) or saline (154 mmol/l); somatostatin (SRIH) (500 micrograms/h); and SRIH plus glucagon (3 ng.kg 1.min-1). Glucagon infusion did not impair glucose tolerance, neither in normal subjects nor in patients with cirrhosis. On the other hand, in both groups glucose tolerance was impaired by SRIH infusion, presumably owing to an absolute insulin deficiency. Both in normal subjects and in cirrhotic patients, SRIH plus glucagon infusion further impaired glucose tolerance, presumably as a result of excess glucagon and concomitant insulin deficiency. In conclusion, our data show that hyperglucagonemia is not an important factor in the development of the glucose intolerance in patients with hepatic cirrhosis. PMID- 2899369 TI - Pancreatic hormone secretion in chronic pancreatitis without residual beta-cell function. AB - Hormonal responses (glucagon, pancreatic polypeptide and somatostatin) to iv glucagon, iv arginine, and ingestion of a mixed meal were investigated in 6 patients with insulin-dependent diabetes secondary to chronic pancreatitis without beta-cell function, in 8 Type I (insulin-dependent) diabetics without beta-cell function, and 8 healthy subjects. No significant differences were found between the two diabetic groups regarding glucagon responses to arginine and meal ingestion. In the patients with diabetes secondary to chronic pancreatitis compared with Type I diabetics and normal controls, the pancreatic polypeptide concentrations were significantly lower and somatostatin concentrations were significantly higher after glucagon, arginine and a mixed meal. Thus, pancreatic glucagon secretion was preserved in patients with insulin-dependent diabetes secondary to chronic pancreatitis, having no residual beta-cell function. These findings suggest that pancreatic glucagon deficiency is not absolute in insulin dependent diabetes secondary to chronic pancreatitis. A high level of somatostatin may contribute to a lower blood glucose level in patients with chronic pancreatitis. PMID- 2899370 TI - Islet secretion of immunoreactive thyrotropin-releasing hormone and the 'paracrine-like' effects of its exogenous administration. AB - In order to know more about the secretory pattern of islet TRH in response to glucose and its possible physiological relevance, the release of this hormone as well as that of insulin, glucagon, and somatostatin was radioimmunologically measured. Whereas the secretion of immunoreactive insulin and somatostatin by incubated rat islets is known to be dose-dependently stimulated by glucose, that of glucagon and TRH was inhibited by glucose. Similarly, palmitate dose dependently inhibited islet glucagon and TRH release. Exogenous TRH exerted strong and dose-dependent effects on islet secretion of the other hormones at the same concentration range at which its hypophysiotropic effects are produced (10( 10) to 10(-8) mol/l). It inhibited the insulin response to glucose and blocked that of glucagon, whereas it enhanced glucose-induced stimulation of somatostatin. These results are suggestive of a possible paracrine inhibitory role of islet TRH, either directly exerted on the secretion of insulin and glucagon or partially mediated through the stimulation of somatostatin release. PMID- 2899371 TI - Decision making in the routine management of myocardial infarction. PMID- 2899372 TI - Difficulties with tooth protectors in endotracheal intubation. AB - The suitability of three tooth protectors for routine use during endotracheal intubation was studied in 300 consecutive patients undergoing elective operations under general anaesthesia. The main disadvantages of the protectors were lack of space and the consequent difficulty of guiding the endotracheal tube into the larynx, and poor visibility, especially when the Camo protector was used. These difficulties could be avoided in most cases by cutting off the right angle of the Camo protector. The less experienced anaesthesiologists especially had difficulties with the protectors: 20% of patients in the Camo group were considered impossible to intubate unless the protector was removed. The silicone inlay of the Camo protector melts and becomes adhesive at body temperature, which makes its prolonged use hazardous. Two patients lost a maxillary incisor despite the proper use of a protector (Denex). Thus the use of a tooth protector alone does not guarantee avoidance of dental trauma. Better results could be obtained by improving the design of the protectors and by careful pre-anaesthetic dental examination. PMID- 2899373 TI - The acute response of Schwann cells to taxol after nerve crush. AB - The effect of taxol, an antimitotic drug which stabilizes microtubules and promotes their assembly, was studied with regard to Schwann cells over a 4-week period following a crush injury to rat sciatic nerve. A single intraneural injection of taxol in dimethyl sulfoxide (DMSO) was given immediately after the crush into the site of injury in one sciatic nerve and was compared with the other side which was crushed but injected with DMSO only. Sampled sites were taken proximal and distal to the lesion, as well as from the lesion itself, and studied by light and electron microscopy. The Schwann cell response was most marked during the degenerative phase immediately following the crush. At this time, there was a decrease of all cytoplasmic structures except microtubules and smooth endoplasmic reticulum. At the site of the crush lesion in taxol-treated nerves, Schwann cells possessed accumulations of myelin debris and lipid droplets. Mitotic Schwann cells were also engorged with myelin breakdown products. Multinucleated Schwann cells, believed to be the result of abnormal mitotic activity, were also apparent and were filled with large numbers of cytoplasmic microtubules. The latter were sometimes regularly arranged around phagocytosed or intracytoplasmic debris. Some recovery from the crush injury was noted with time, although the number of Schwann cells was much lower than would have been anticipated in the absence of taxol, in that long stretches of naked axon bundles were common and microtubule-related abnormalities persisted up to 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899375 TI - Gastric aspirates of newborn infants: pH, volume and levels of gastrin- and somatostatin-like immunoreactivity. AB - The aim of the present investigation was to study volume, pH and the levels of gastrin- and somatostatin-like immunoreactivity in gastric aspirates obtained immediately after birth from 25 healthy infants. In addition, the same parameters were measured in amniotic fluid collected from 11 of the mothers. The median volume of the gastric contents was 4 ml (range 0-11) and median pH was 6.96 (range 2.77-9.58). Gastrin and somatostatin median concentrations were 8 pM (range 0-52) and 67 pM (range 15- greater than 1,000), respectively. The corresponding levels in amniotic fluid were 8.2 +/- 3.6 pM and 28.4 +/- 5.3 pM, median pH was 9.22 (range 8.05-9.58). There was a significant correlation between volume and pH of gastric contents. The pH of the gastric aspirate was inversely correlated with the somatostatin levels. No correlation could be demonstrated as regards levels in amniotic fluid and gastric content. Gastric content and amniotic fluid were not correlated regarding pH, gastrin and somatostatin. It is suggested that the foetus drinks about 10 ml portions of amniotic fluid which are gradually emptied from the stomach and that these drinking episodes are associated with gastric exocrine and endocrine secretion normally seen following feeding after birth. PMID- 2899374 TI - The acute effects of taxol upon regenerating axons after nerve crush. AB - The effects of taxol, a compound renowned for its ability to promote microtubule assembly, were studied upon axons after its injection into rat sciatic nerve immediately following a local nerve crush injury. The single injection of taxol was delivered into the lesion site and the animals were sampled up to 4 weeks post-injection (PI) for morphological study. At the lesion site, Wallerian degeneration was encountered and this was followed by axonal sprouting by 5 days PI. In contrast to axonal sprouting seen in uninjected controls (crush-only), sprouts in taxol-injected nerves rapidly became swollen due to an increasing number of axoplasmic microtubules. By 2 weeks PI, this led to the formation of giant axonal bulbs from which by 3 weeks PI, a secondary wave of regenerative growth occurred consisting of thin, haphazardly twisted axonal twigs largely lacking Schwann cell investment. These were most numerous after 3 and 4 weeks PI. Within the affected axoplasm, microtubules occasionally formed occasional channels around mitochondria. The present results, characterized by the more rapid appearance of taxol-induced giant axonal bulbs in regenerating sprouts than seen after taxol injection of intact nerve, suggest that regenerating PNS axons are exquisitely sensitive to and dramatically affected by taxol. The conclusions support previous observations on a crucial role for microtubules during early axonal growth. PMID- 2899376 TI - Outbreak of infections due to P-fimbriated Escherichia coli O16:K1 in a neonatal intensive care unit. PMID- 2899377 TI - Antipsychotic withdrawal symptoms: phenomenology and pathophysiology. AB - The authors review the literature discribing non-dyskinetic antipsychotic withdrawal phenomena. Withdrawal of these agents can cause nausea, emesis, anorexia, diarrhea, rhinorrhea, diaphoresis, myalgia, paresthesia, anxiety, agitation, restlessness, and insomnia. Psychotic relapse is often presaged by increased anxiety, agitation, restlessness and insomnia, but the temporal relationship of these prodromal symptoms to reduction in the dosage or discontinuation of neuroleptics distinguishes them from the effects of abrupt withdrawal. PMID- 2899378 TI - Do concentrations of neurotransmitters measured in lumbar cerebrospinal fluid reflect the concentrations at brain level? AB - CSF concentrations of vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), noradrenaline (NA) and dopamine (DA) were measured in the lateral ventricles and at the lumbar level in patients with normal pressure hydrocephalus (NPH). The concentrations of VIP (n = 15), NA (n = 10) and DA (n = 10) were significantly higher at the lumbar level than at the ventricular level, whereas the concentrations of CCK (n = 9) were similar at the two sites. A significant positive correlation between the concentrations measured at the two levels was found for VIP (rs = 0.65; p less than or equal to 0.01) and DA (rs = 0.94; p less than or equal to 0.001). The results indicate that the concentrations of transmitter substances measured in CSF at the lumbar level not necessarily are indicative for concentrations measured more centrally. The negative correlations between Evans ratio and L-CSF VIP (rs = -0.76; p less than or equal to 0.001), and between resistance to outflow and V-CSF as well as L-CSF CCK (rs = -0.75); p less than or equal to 0.05) might be explained by a reduction in number of cortical neurons or by disturbances in CSF dynamics in patients with NPH. PMID- 2899379 TI - Structure and expression of genes involved in T lymphocyte recognition and activation. PMID- 2899380 TI - On the relationship between incorporation of 32P into phospholipids and binding of beta-adrenoceptor blocking drugs to isolated mast cells. AB - The lipophilic beta-adrenoceptor blocking drugs exaprolol and propranolol significantly decreased the incorporation of 32P into phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol of isolated rat mast cells. In contrast, the hydrophilic drugs metipranolol, practolol and atenolol increased the incorporation of 32P into phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol. The inhibition of 32P incorporation by lipophilic drugs correlated with the high binding of these drugs to mast cells. PMID- 2899381 TI - Histamine dependent cyclic AMP generating system in rabbit CNS: interaction with neuroregulators and forskolin. AB - Histamine (HI) potently stimulated, through H2-receptors, cAMP accumulation in rabbit cerebral cortical slices but not in retinal pieces. The action of HI in the cerebral cortex was not significantly affected by dopamine, serotonin, melatonin and GABA-ergic drugs. Forskolin markedly stimulated cAMP accumulation both in the cerebral cortex and retina. There was a synergistic interaction between HI and forskolin in the cerebral cortex, whereas in the retina HI decreased the forskolin-activated cAMP accumulation. PMID- 2899382 TI - Action of histamine on nerve mediated responses of the guinea-pig ileum. AB - The effect of histamine on the responses of the guinea-pig ileum to stimulation of intramural nerves and to some potential nonadrenergic, noncholinergic (NANC) neurotransmitters was analysed. During sustained tonic histamine contraction, electrical stimulation of all intramural nerves elicited a biphasic response (contraction followed by after-relaxation) and application of ATP and bradykinin caused relaxation of the ileum in contrast to their contractile effect on basal tension. Histamine reduced contractile and augmented relaxatory NANC responses, and prevented capsaicin from producing any contractile effect and from significantly influencing the NANC contractions. The present results suggest that, besides its direct effect, histamine activates intramural nerve fibres, mainly the sensory ones, and unmasks NANC relaxation thus modifying the mechanical activity. PMID- 2899383 TI - Central effects of histamine H2-receptor agonists and antagonists on nociception in the rat. AB - The effects of intracerebroventricular injection of histamine H2-receptor agonists (4-methylhistamine, 4-MeH; dimaprit, DIM), H2-antagonists (cimetidine, CIM; ranitidine, RAN; famotidine, FAM) and of the DIM chemical analogue SK&F 91487 on hot-plate latency in rats were examined. Both DIM (0.4-0.8 mumol/rat) and 4-MeH (0.4-0.8 mumol/rat) significantly enhanced the pain threshold, whereas SF&F 91487 (0.8 mumol/rat) had no effect, indicating that DIM antinociception is specifically due to its activity on histamine (HA) receptors. The H2-antagonists CIM (0.8 mumol/rat) and RAN (0.6 mumol/rat) also enhanced the pain threshold, while FAM (0.03 mumol/rat) did not modify pain latency. When injected before 4 MeH, FAM reduced the antinociceptive effect of 4-MeH. These findings suggest that the antinociceptive activity of CIM and RAN is not related to specific blockade of H2-receptors and that the activation of HA-H2-receptors is inhibitory to nociception. PMID- 2899384 TI - The possibilities of predicting allergic effects of new antirheumatics. AB - The new antirheumatic drugs Benzofenac and Flobufen were assessed for their possible influence on various immunological parameters. They were shown to enhance passive cutaneous anaphylaxis (PCA) to ovalbumin in rats and to suppress the numbers of helper and suppressor T-lymphocytes in mice. The effect of Benzofenac in the latter system was found to be more pronounced. The drugs had no effects in any of the other test systems, including the development of delayed hypersensitivity, mitogen-induced lymphocyte proliferation in vitro and the production of antisera (as tested by PCA). PMID- 2899385 TI - Pulmonary reactions induced by drugs: a clinical compendium. AB - With the increasing number of drugs, the list of agents which are capable of inducing pulmonary reactions continues to lengthen. This article is a compendium of presently available information on drug induced pulmonary reactions which we have found clinically useful. We have divided the drugs in groups on the basis of two features, pharmacologic actions and type of pulmonary reactions. A total of 109 drugs are cited. Categories of pharmacologic actions include cytotoxic drugs, analgesic and antirheumatic drugs, antimicrobial agents, vasoactive drugs, tranquilizers, anticonvulsants, antidepressants, antiarrhythmics, oral antidiabetics and a group of miscellaneous drugs. Type of pulmonary reactions include pulmonary eosinophilia, bronchoconstriction, acute interstitial pulmonary disease, mediastinic involvement, pleural effusion, pulmonary hypertension, pulmonary calcifications, pulmonary infections and drugs reported to cause drug induced Systemic Lupus Erythematosus. PMID- 2899386 TI - Secondary prevention in elderly survivors of heart attacks. AB - More than 200,000 elderly patients survive myocardial infarctions each year. Thus, the achievement of even minimal decreases in reinfarction and mortality rates will benefit large numbers of patients. Secondary prevention strategies include smoking cessation; the control of hyperlipidemia, obesity and diabetes; the management of hypertension and stress; exercise; the use of drugs such as beta blockers and aspirin, and increased attention to general health. PMID- 2899387 TI - New alpha 1-adrenergic receptor antagonists for the treatment of hypertension: role of vascular alpha receptors in the control of peripheral resistance. AB - The pharmacology, clinical efficacy and safety of new alpha-adrenergic receptor antagonists for the treatment of hypertension was reviewed (Table XIV). Although all these agents block alpha 1 receptors, some of them have additional effects on histamine, serotonin, dopamine, and alpha 2 receptors. These other actions account for the differences in the side effect profiles observed, i.e., increased incidence of central nervous system side effects found with indoramin, ketanserin, and urapidil, as well as for some additional beneficial effects of ketanserin (i.e., antiplatelet aggregation activity). The magnitude of BP reduction observed with antagonists of alpha 1-adrenergic receptors is modest. In most studies, the degree of BP reduction is comparable to that of prazosin, but less than that achieved with thiazide diuretics, beta-receptor antagonists, or methyldopa. Studies on the comparative efficacy and safety of new alpha 1 antagonists with converting enzyme inhibitors or calcium-channel blockers are not available. In general, alpha 1 antagonists produce greater reductions in standing than in supine BP, an effect due to the venodilatory action of these drugs. New alpha 1 antagonists appear to have equal efficacy in black and white hypertensive individuals. Their comparative efficacy and safety in young vs elderly hypertensive individuals requires further investigation. No information about the possible development of tolerance during treatment with new alpha 1 blockers was encountered. The effects of alpha 1 antagonists on HR are variable and depend on how long after the oral dose the measurements were obtained. In most studies, no significant HR changes are noticed for readings obtained 24 hours post dose; whereas tachycardia has been observed at the time of peak hypotension. Since alpha 1 antagonist-induced tachycardia is most likely of reflex nature, i.e., mediated to an increase in sympathetic activity, the increased HR may be associated with increases in myocardial contractility and in myocardial oxygen consumption. Consequently, a 24-hour HR monitoring during treatment with alpha 1 antagonists should be required for evaluation of new agents. The hemodynamic, humoral, and hormonal effects of the newer alpha 1-receptor antagonists are comparable to those of prazosin. The most consistent finding is a reduction in total peripheral resistance associated with either no change or with only small increases in cardiac index. These agents have been shown either not to change or to increase renal blood flow.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2899388 TI - Pathophysiologic and pharmacotherapy considerations in the management of the black hypertensive patient. AB - The mortality and morbidity of hypertension-related diseases among blacks are much higher than in age- and sex-matched white counterparts. New data show that the incidence of renal damage may be 18 to 20 times greater in blacks than in whites. Some preliminary data also indicate that coronary heart disease is much more prevalent in blacks than previously suspected and that coronary heart disease mortality among blacks may indeed not be declining, as it is for white populations. Major contributors to these findings in blacks are an increased prevalence and severity of hypertension, a possibly increased susceptibility to end-organ damage, socioeconomic factors and beliefs that affect hypertension control, and very possibly some obsolete treatments that focus on blood pressure numbers and do not emphasize the black person and the associated risk factors. Diuretic therapy has long been the mainstay treatment for black hypertensives, but the effects of diuretics on lipid levels and left ventricular hypertrophy, among other factors, should be carefully assessed. A recent study of beta blockers in blacks showed that metoprolol was effective and well tolerated. Consideration of epidemiologic, pathophysiologic, and pharmacotherapeutic features of hypertension in blacks may require traditional views of this disease and its treatment in this special population to be reevaluated. PMID- 2899389 TI - Central nervous system considerations in the use of beta-blockers, angiotensin converting enzyme inhibitors, and thiazide diuretics in managing essential hypertension. AB - The most common mild side effects occurring with use of beta-blockers, thiazide diuretics, and angiotensin-converting enzyme inhibitors for blood pressure control are central nervous system symptoms, specifically lethargy, sedation, and fatigue. These symptoms affect 5% to 10% of patients taking these drugs. The mechanism by which beta-blockers may induce central nervous system effects is uncertain. Relative lipophilicity as a factor affecting penetrance of the blood brain barrier has not proved to be a reliable predictor of whether the drug will cause such disturbances. Comparisons of atenolol (hydrophilic) and metoprolol (lipophilic) have shown no differences between these drugs with respect to side effects of the central nervous system. The incidence of central nervous system effects with angiotensin-converting enzyme inhibitors is similar to that for most beta-blockers. The precise role of the angiotensin-converting enzyme in the central nervous system is not well defined. Most thiazide diuretics are not associated with major complications of the central nervous system, although electrolyte imbalance may occasionally lead to complaints of neurologic symptoms. Because the incidence of central nervous system effects with these three classes of drugs is so low, concern for the side effects of the central nervous system is not a prime consideration in the choice of an initial antihypertensive agent. PMID- 2899390 TI - Impact of beta-blockade on complex cognitive functioning. AB - Fifty adult men with mild to moderate hypertension were recruited to participate in a double-blind crossover study. Each subject received 14 days of drug treatment and 14 days of placebo treatment (random order). Half the subjects were assigned to a metoprolol (150 mg/day) vs placebo treatment regimen and half to an atenolol (100 mg/day) vs placebo regimen. Blood pressure levels as well as measures of simple (proofreading), intermediate (visual-motor task), and complex (management simulation) task performance were obtained at the end of the drug and placebo treatment periods. Metoprolol treatment generated better scores than did placebo or atenolol treatment for proofreading, visual-motor performance, and several measures of complex managerial competence. Atenolol treatment generally resulted in performance levels that did not differ from those observed with placebo. However, atenolol-treated subjects made more errors than did placebo treated subjects in the visual-motor task and also showed some deterioration on one measure of complex managerial functioning. PMID- 2899391 TI - The role of sympathetic activity in atherogenesis: effects of beta-blockade. AB - Clinical and experimental evidence points to potential antiatherosclerotic effects of certain beta-adrenoreceptor antagonists. Long-term treatment with metoprolol resulted in significant reductions of total and cardiovascular mortality or morbidity due to decreased incidence of coronary and cerebrovascular complications both in a primary prevention trial in hypertensive patients and in a secondary prevention trial in patients surviving myocardial infarction. The observations suggest that a retardation of atherosclerosis development might have contributed to the reduced incidence of cardiovascular complications. An antiatherosclerotic effect of beta-blockers has been directly demonstrated in animal studies. In cholesterol-fed rabbits, metoprolol significantly reduced the development of atherosclerotic plaques in the aortic intima in the absence of any changes in blood lipids. Similar findings were reported for propranolol, which prevented psychosocial stress-induced atherosclerosis of the coronary artery in monkeys. Furthermore, beta-blockers have been shown to prevent stress-induced endothelial injury and platelet accumulation to intima at atherosclerotic predilection sites in animal models. These antiatherogenic effects may be due to biochemical and hemodynamic factors. Two biochemical effects of beta-blockade may lead to reduced cholesterol accumulation in arterial intima at unchanged serum cholesterol levels. One is a beta-blocker-induced increase of prostacyclin biosynthesis, and the other a metabolic change of low-density lipoprotein, reducing its potential for deposition in the arterial wall. The antiatherogenic effect of these factors may be reinforced by beta-blocker-induced hemodynamic changes leading to reductions of arterial flow aberrations and pressure-related wall stress. PMID- 2899392 TI - Effects of stress and the sympathetic nervous system on coronary artery atherosclerosis in the cynomolgus macaque. AB - Epidemiologic evidence increasingly implicates psychosocial variables in the development of coronary heart disease in human beings, an association that appears to be independent of the effects of other coronary disease risk factors. It has been hypothesized that behavioral influences on coronary heart disease are mediated by activation of the sympathetic nervous system, perhaps through exacerbation of coronary artery atherosclerosis. This article summarizes several studies of the effects of stress and sympathetic arousal on atherosclerosis in a nonhuman primate model of atherogenesis. The application of a behavioral stressor involving periodic reorganization of social group memberships resulted in worsened coronary atherosclerosis among male cynomolgus monkeys (Macaca fascicularis) fed a cholesterol-containing diet, relative to control animals housed in groups of fixed (stable) membership, but only among those monkeys that retained dominant social status during the course of the study. This effect could not be attributed to concomitant variability in blood pressure or serum lipid concentrations. When the same experimental procedures were applied to males fed a diet low in saturated fat and cholesterol, the manipulation of group memberships similarly led to development of greater atherosclerosis in the coronary arteries. In related observations, monkeys that exhibited the largest heart rate responses to a standardized behavioral challenge had more extensive coronary atherosclerosis than animals showing a less pronounced cardiac responsivity to stress. In a final investigation, we observed that the exacerbated atherosclerosis of dominant monkeys consuming an atherogenic diet and housed in unstable social groups could be prevented by long-term administration of a beta adrenoreceptor-blocking agent, propranolol hydrochloride. PMID- 2899393 TI - A comparison of the identification of group A streptococci and enterococci by two rapid pyrrolidonyl aminopeptidase methods. AB - Group A streptococci and enterococci can be differentiated from other streptococci by their ability to cleave L-pyrrolidonyl-beta-napthylamide (PYR). The authors evaluated two pyrrolidonyl aminopeptidase (PYRase) systems--Minitek (BBL Microbiology Systems, Cockeysville, MD) and Identicult-AE (Scott Laboratories, Inc., Fiskeville, RI)--for the presumptive identification of Group A streptococci and enterococci. Eighty-three Group A streptococci, 77 beta hemolytic non-Group A streptococci, 74 enterococci, 56 nonenterococcal non-beta hemolytic streptococci, 1 Streptococcus pneumoniae, and 1 Aerococcus were tested. Compared with results obtained with reference methods (bile esculin agar and 6.5% [w/v] sodium chloride for identification of enterococci, and latex agglutination tests by Streptex [Burroughs Wellcome, NC] for grouping of beta-hemolytic streptococci) both the Identicult-AE and MInitek systems were 100% sensitive and specific for identification of both enterococci and Group A beta-hemolytic streptococci. Advantages of the Identicult-AE system compared with Minitek were the use of a smaller inoculum for which subculture was not necessary, incubation at room temperature rather than at 37 degrees C, and lower cost. Both PYRase kits tested, and in particular the Identicult-AE system, were very easy to use and should be considered as rapid, reliable, and cost-effective alternative methods for the presumptive identification of Group A streptococci and enterococci in the clinical laboratory. PMID- 2899394 TI - Entomologic studies after a St. Louis encephalitis epidemic in Grand Junction, Colorado. AB - In 1986, after a St. Louis encephalitis epidemic in Grand Junction, Colorado, in 1985, vector mosquitoes in the city were surveyed to correlate their bionomics and infection rates with the occurrence of human disease. No human cases were reported, but mosquito surveillance disclosed St. Louis encephalitis virus in Culex tarsalis and Culex pipiens pipiens. Mosquitoes were collected with gravid traps designed to attract Cx. p. pipiens and with Centers for Disease Control light traps. Culex p. pipiens was the predominant vector mosquito collected and was captured chiefly in gravid traps. The Culex tarsalis population emerged and expanded approximately one month earlier than did the Cx. p. pipiens population. Consequently, Cx. p. pipiens was the predominant vector species after August. Infection rates throughout the surveillance period (June to September) were severalfold higher in Cx. tarsalis than in Cx. p. pipiens; however, in late summer, diminished numbers of Cx. tarsalis and a persistent population of Cx. p. pipiens resulted in relatively larger numbers of infected Cx. p. pipiens. Thus, the participation of Cx. p. pipiens as a St. Louis encephalitis vector would have been underestimated in previous studies employing light traps alone. These studies provide further evidence that Cx. p. pipiens-associated urban St. Louis encephalitis and rural Cx. tarsalis-associated St. Louis encephalitis cycles may coexist in the West. PMID- 2899395 TI - Placental transfer of beta-adrenergic antagonists studied in an in vitro perfusion system of human placental tissue. AB - Maternofetal transfer of five beta-blockers differing in molecular weight, solubility, and binding to albumin was studied using a dual in vitro perfusion system of an isolated cotyledon of human placenta. At steady state the diffusion rate of the lipid-soluble propranolol, timolol, and labetalol was three to four times higher than that of the hydrophilic atenolol and celiprolol. Albumin binding had no significant effect on diffusion when equal concentrations were used in the two perfusion circuits. With increased albumin concentration on the fetal side an acceleration of the diffusion of propranolol could be shown. Propranolol and labetalol showed considerable binding to placental tissue. After bolus injection transfer was clearly suppressed, as a result of tissue binding, and there was a delay until a steady state of diffusion was reached when constant concentrations were maintained in the maternal compartment. With recirculation of the fetal and maternal compartments propranolol rapidly equilibrated in the two perfusion circuits at 35% of the initial level in the maternal circuit. Atenolol after 4 hours of recirculation had not reached full equilibration between the two compartments, and the fetal concentration was at 55% of the initial level on the maternal side. PMID- 2899396 TI - Entry level education inadequate for practice in pediatrics. PMID- 2899397 TI - Effect of PGE2 and alpha-adrenergic agonists on AVP-dependent cAMP levels in rabbit and rat CCT. AB - The effect of prostaglandins and alpha-adrenergic agonists on arginine vasopressin-induced adenosine 3',5'-cyclic monophosphate (cAMP) production was investigated in microdissected rat and rabbit cortical collecting tubules (CCT) incubated in vitro. In rabbit CCT, addition to all media of a prostaglandin synthesis inhibitor increased this production; exogenous prostaglandin E2 (PGE2) induced a reproducible dose-dependent inhibition of cAMP accumulation. Maximal inhibition (mean: 57.5%) was observed with 0.3 microM PGE2, and threshold inhibition was observed with concentrations ranging from 3 to 10 nM PGE2. Inhibition of cAMP levels in rabbit CCT was also obtained with 0.3 microM PGF2 alpha (mean inhibition: 44.3%) but not with alpha-adrenergic agonists studied under the same conditions. The opposite was observed in rat CCT studied in parallel: the alpha-agonists inhibited cAMP production by up to 80%, but PGE2 had no effect. PMID- 2899398 TI - Alpha 2-agonists block ADH action in toad bladder and this inhibition is not modified by indomethacin. AB - To identify the type of alpha-adrenoceptors involved in the inhibition of the hydrosmotic effect of antidiuretic hormone (ADH) on the toad bladder, we studied the effect of different alpha-adrenergic agonists and antagonists on ADH-induced water transport. Serosal addition of epinephrine (10(-6) M) and norepinephrine (10(-6) M) in the presence of 10(-4) M propranolol significantly inhibited the hydrosmotic effect of ADH (arginine vasopressin). This inhibitory effect of the catecholamines was completely reversed by 10(-5) M yohimbine but not by prazosin. Clonidine did not block ADH-induced water transport, but guanabenz, another alpha 2-agonist, inhibited water transport in response to ADH. In bladders pretreated with indomethacin to block prostaglandin synthesis, basal water permeability was increased, and even in this condition epinephrine inhibited ADH-induced water transport. These studies indicate that alpha 2-adrenergic receptors are involved in the inhibitory effect of catecholamines on ADH-mediated water permeability in the toad bladder. However, this effect was not mimicked by clonidine, as in the case of rabbit cortical collecting tubule. The inhibitory effect of epinephrine appears to be exerted independently of prostaglandin synthesis. PMID- 2899399 TI - Regulation of cholesterol metabolism in fetal rabbit aorta: role of amniotic fluid factors. AB - This study shows that amniotic fluid enhances cholesterol esterification in arterial wall, as measured by in vitro assay of acyl-CoA:cholesterol acyltransferase (ACAT) activity and by incorporation of oleic acid to cholesteryl esters in cultured fetal aortas and smooth muscle cells. This property is mostly evident in the fraction of molecular weight greater than 100,000, and it is abolished by delipidation, indicating that stimulating factor is probably lipoprotein in nature. Despite an increased cholesterol esterification by the presence of amniotic fluid in medium of cultured fetal aortas, the content of cholesterol and cholesteryl esters was much lower. The cellular structures are better preserved in explants cultured with amniotic fluid than in control animals. This study indicates that amniotic fluid contains factors that may have a pronounced effect on arterial wall during development. PMID- 2899400 TI - Circulatory and metabolic responses to carbon monoxide hypoxia during beta adrenergic blockade. AB - The role(s) of beta-adrenoceptors in whole body and hindlimb skeletal muscle cardiovascular and metabolic responses during carbon monoxide hypoxia (COH) was studied in anesthetized dogs. One group of animals was beta-blocked with propranolol (beta 1- and beta 2-blockade), a second was given ICI 118,551 (beta 2 blockade), and a third served as a time control. Immediately after a control sampling period, COH was induced (about a 63% decrease in arterial O2 content), and additional measurements were then obtained at 30 and 60 min of hypoxia. Cardiac output values were not different between the three series at control; an increase (P less than 0.05) occurred in all groups during COH. This rise was greatest in the COH group; the values for the propranolol- and ICI 118,551 blocked groups were not different from each other during COH. Hindlimb blood flow rose (P less than 0.05) during COH only in the control group. Both whole body (30 min) and hindlimb (30 and 60 min) resistance values were greater during hypoxia in the beta-blocked groups (P less than 0.05) than in the control series. Furthermore, whole body oxygen uptake decreased (P less than 0.05) in both beta blocked groups during COH. We conclude that approximately 35% of the rise in cardiac output occurring during COH depended on peripheral vasodilation mediated through beta 2-adrenoceptors. PMID- 2899401 TI - Creatine kinase elevation after neuroleptic treatment. AB - Two cases of asymptomatic elevation of creatine kinase levels after oral neuroleptic treatment are described. One patient was successfully challenged with a different neuroleptic. The authors discuss possible reasons for creatine kinase elevation. PMID- 2899402 TI - Long-term claustrophobia following magnetic resonance imaging. PMID- 2899403 TI - Efficacy of anticholinergic prophylaxis for neuroleptic-induced acute dystonia. AB - The authors analyzed data from nine studies comparing the incidence of acute dystonia induced by neuroleptic agents with and without concomitant use of anticholinergic agents. Anticholinergic agents reduced the rate of dystonia by 1.9-fold in all patients treated with different neuroleptics and by 5- to 8-fold in patients treated with high-potency neuroleptics. In addition, the incidence of dystonia and the efficacy of anticholinergic prophylaxis were related inversely to age. These results support the efficacy of anticholinergic agents in preventing neuroleptic-induced dystonia, particularly in young male patients treated with high-potency neuroleptics. PMID- 2899404 TI - Total intravenous anaesthesia using propofol infusion--50 consecutive cases. AB - Fifty consecutive patients in the authors' practice were anaesthetised with a total intravenous technique using propofol infusion, fentanyl, vecuronium and oxygen in air. Patients were predominantly elderly and undergoing major upper gastrointestinal surgery for a mean duration of 133 minutes (range 20 minutes to 7 hours). Twenty-one patients had significant concomitant medical illness. Propofol was found to give a rapid, smooth induction with wide variation in dose requirement (0.5 to 2.9 mg/kg). There was a mean systolic blood pressure fall of 27% from preoperative values, greatest in elderly patients. Depth of anaesthesia was readily adjusted by alteration in infusion rate according to standard clinical criteria. The dose of propofol required for maintenance was highly variable (range 2-15 mg/kg/hr in the first hour). Three patients reported dreaming and two of these had shown signs of light anaesthesia. Recovery was rapid, with few side-effects, and a mean time to open eyes on command of 8.5 minutes from the end of infusion. Propofol was considered to be a satisfactory intravenous agent for the induction and maintenance of anaesthesia in the majority of patients studied. The most significant problem was hypotension following the induction dose. PMID- 2899405 TI - Dental damage and laryngoscopy. PMID- 2899406 TI - Acetyl coenzyme A synthetase catalyzed reactions of coenzyme A with alpha, beta unsaturated carboxylic acids. AB - alpha, beta-Unsaturated coenzyme A (CoA) thioesters including acrylyl CoA, methacrylyl CoA, and propiolyl CoA were synthesized by catalysis with acetyl CoA synthetase (EC 6.2.1.1.). After isolation from the enzymatic reactions, the products were found to be the result of 1,4 addition of CoASH to the double bond and addition of water to the triple bond of the initial acyl CoA adducts. Structural determinations of these products by 1H NMR, 13C NMR, and the chemical reactions leading to their formation are described. PMID- 2899407 TI - Electrophoresis of DNA restriction fragments in poly-N-acryloyl-tris gels. AB - Poly-N-acryloyl-tris(hydroxymethyl)aminomethane (NAT) gels were evaluated as a matrix for DNA electrophoresis. The resolution of DNA restriction fragments in three poly(NAT)-N,N'-methylenebisacrylamide (Bis) gels (4, 5, and 6%) was compared with the resolution in polyacrylamide (AA)-Bis gels of the same percentage. Poly(NAT) gels were found to give a substantially improved separation of DNA fragments larger than 200 bp. In contrast to poly(AA) gels, DNA fragments of up to 4 kbp were well resolved in the new matrix. By pulse-field electrophoresis the useful separation range of poly(NAT) gels was expanded to at least 23 kbp. For DNA fragments below 10 kbp, the resolution was better than that in a 0.7% agarose gel. Thus poly(NAT) gels are most suitable for the electrophoretic separation of DNA molecules whose size is out of the optimal fractionation range of poly(AA) or agarose gels. PMID- 2899408 TI - The increase in urinary alanine aminopeptidase excretion associated with enflurane anesthesia is increased further by aminoglycosides. AB - Urinary excretion of alanine aminopeptidase (AAP) is an extremely sensitive indicator of drug-induced renal tubular damage. The urinary excretion of AAP was determined in patients after enflurane anesthesia with or without concurrent aminoglycoside administration to determine if enflurane enhances the nephrotoxic potential of aminoglycosides. Twenty-two patients with normal renal function were studied. Ten received enflurane alone, eight received enflurane plus gentamicin or tobramycin, and four patients who underwent nitrous oxide and narcotic anesthesia were the control group. Preoperative values ranged from 1010 to 2461 microU/24 hour. Urinary AAP excretion increased significantly in both enflurane groups 2 days postoperatively (P less than 0.025). Patients who received both enflurane and aminoglycosides had significantly greater urinary AAP excretion on postoperative day 2 than did patients given enflurane alone: 21,342 +/- 4074 microU/24 hour and 6336 +/- 1496 microU/24 hour, respectively (mean +/- SEM, P less than 0.005). There was no change in AAP excretion in the control group compared to baseline; on day 3 AAP was 1412 +/- 710 microU/24 hour. No changes in blood urea nitrogen or serum creatinine levels were observed. These data suggest that enflurane increases the renal tubular effects of aminoglycosides, possibly increasing the risk of aminoglycoside renal toxicity. PMID- 2899409 TI - A simple and rapid high-pressure liquid chromatographic assay for pentobarbital and other barbiturates in serum. AB - A single extraction technique for measuring pentobarbital and other barbiturates in serum involved high-pressure liquid chromatography and UV detection yielding a sensitivity for pentobarbital of about 1 microgram/ml. We concluded that the assay provides a practical method for use in pharmacokinetic studies and in serum concentration monitoring in experimental animals. PMID- 2899410 TI - Elevated serum levels of soluble Tac peptide in adult T-cell leukemia: correlation with clinical status during chemotherapy. AB - Adult T-cell leukemia associated with human T-cell leukemia virus type I (HTLV-I) is characterized by a clonal expansion of a CD4-positive subset of T lymphocytes that constitutively express high numbers of interleukin-2 receptors and that frequently infiltrate the skin; osteolytic bone lesions, and hypercalcemia. Using an enzyme-linked immunosorbent assay (ELISA) test, we measured the level of soluble Tac peptide, one chain of the human interleukin-2 receptor, in the serum of 50 patients with adult T-cell leukemia (38 Japanese and 12 American patients), 8 patients with other hematologic malignancies, 8 asymptomatic HTLV-I-antibody positive carriers, and 17 normal controls. The serum level of soluble Tac peptide (geometric mean U/mL, 95% CI) was elevated at presentation in all patients with adult T-cell leukemia (16,461; 819 to 330,896) when compared with normal controls (238; 112 to 502), patients with other hematologic malignancies (1302; 475 to 3569), and healthy HTLV-I antibody-positive carriers (490; 115 to 2086). The highest levels were seen in patients (n = 33) with acute (32,154; 2587 to 399,598) compared with chronic (5464; 661 to 45,156) disease (n = 14). Serum levels of Tac peptide also tended to be more elevated in patients with adult T cell leukemia with hypercalcemia (32,072; 2461 to 417,908) compared with normocalcemic patients (13,885; 496 to 388,436). Serial measurements of soluble Tac peptide levels in serum were done in four patients with adult T-cell leukemia during chemotherapy and the levels reflected disease activity. These observations suggest that the measurement of soluble Tac peptide levels in patients with adult T-cell leukemia is useful as a noninvasive measure of tumor burden and will help in the diagnosis of the disease and management of these patients. PMID- 2899411 TI - [Early biochemical indicators of renal injury]. PMID- 2899412 TI - Plasma somatostatin behaviour in diabetes. PMID- 2899413 TI - [Comparison of the efficacy of two H2 antagonists of histamine in allergic rhinitis. Considerations on the mechanism of action]. AB - A random study has been made on perennial atopic rhinitis patients divided into two homogeneous groups and treated with HH2 antagonists of different chemical structure: Cimetidine and Ranitidine. An identity of clinical and humoral results was noted in the two groups. This leads us to believe that the effects induced by the two drugs are linked to the properties of H2 antagonists and not to other potential action as hypothesised for Cimetidine by Drazen. The improvement in all subjective and objective parameters, decrease in total serum IgE, the delayed onset of clinical improvement and its duration in time, suggest that the vascular type action mechanism hypothesised by some Authors is quite secondary to the immunomodulatory one. H2 antagonists in fact induce, together with the clinical improvement and the total serum IgE decrease, a modulatory effect on the T lymphocyte subsets with a variation in the OKT4/OKT8 ratio towards the latter subset that identifies the suppressor cells. Since lymphocyte histamine receptors are uniquely present on suppressor T-cell, it is on these the H2 antagonists would act, modulating the suppressive function positively. PMID- 2899414 TI - [Synthesis of new beta-blockaders analogs of bevantolol or alprenolol]. PMID- 2899415 TI - [Synthesis and pharmacological study of glutamic acid palmitamide and linoleamide]. PMID- 2899417 TI - Quantitation by immunoblotting of the in vivo induction and subcellular distribution of hepatic acetyl-CoA carboxylase. AB - The in vivo induction of rat liver acetyl-CoA carboxylase (ACC) the rate-limiting enzyme of fatty acid biosynthesis, has been examined by immunoblotting, avidin blotting, and enzyme isolation. Three high-molecular-weight immunoreactive bands (Mr 220,000-260,000) were recognized in liver extracts by an anti-carboxylase polyclonal antiserum. Two bands, A and B, comigrated on sodium dodecyl sulfate polyacrylamide gels with purified acetyl-CoA carboxylase, were avidin binding, and were dramatically induced following high carbohydrate refeeding. Only band A was recognized on immunoblots using a monoclonal antibody directed against acetyl CoA carboxylase, suggesting that band B is a proteolytic fragment in which the epitope recognized by the monoclonal antibody is absent. Following refeeding, approximately 57% of acetyl-CoA carboxylase mass (band A + band B) was present in the high-speed supernatant fraction, while 34 and 9% were in the high-speed (microsomal) and low-speed pellet fractions, respectively. Refeeding caused a large increase in total acetyl-CoA carboxylase mass, the magnitude of which differed in the various fractions. In the low-speed supernatant, a 20-fold increase in ACC mass was observed, while a 12-fold increase was seen in the high speed supernatant. The fold increase in the high-speed pellet was even greater (greater than 27-fold). Acetyl-CoA carboxylase purified by avidin-Sepharose chromatography from fasted/refed rats had an approximate 4-fold higher Vmax and a significantly lower Ka for citrate than enzyme purified from fasted animals. The results of this study indicate that the induction of hepatic ACC that occurs during high carbohydrate refeeding of the fasted rat predominantly involves increases in enzyme content in both cytosol and microsomes, but is also accompanied by an increase in enzyme specific activity. PMID- 2899416 TI - Isolation and characterisation of dog uropathogenic Escherichia coli strains and their fimbriae. AB - A number of Escherichia coli strains have been isolated from dogs with urinary tract infections. These strains have been characterised with respect to their O, K, H, and fimbrial antigens, colicin production, antibiotic resistance, plasmid content and their ability to haemagglutinate erythrocytes from various species. Crossed immunoelectrophoresis of fimbrial extracts, as well as the reaction of partly purified fimbriae of a number of these strains with monoclonal antibodies revealed homology or a strong crossreaction with an F12 fimbrial subunit protein of human uropathogenic E. coli strains. Unlike human F12 fimbriae producing strains, the dog isolates did agglutinate dog erythrocytes in the presence of D mannose but not human erythrocytes, indicating that the adhesin carried by these strains is different from the adhesin on fimbriae of human uropathogenic E. coli. Similar indications were obtained from experiments with latex beads coated with the receptor for P-fimbriae. These beads were agglutinated by Escherichia coli strains from human urinary tract infections, but not by the dog isolates described here. Preliminary adhesion experiments of human and dog Escherichia coli to human bladder epithelial and canine kidney epithelial cells also showed differences in adhesion depending on the origin of the strain tested. PMID- 2899418 TI - Ca2+-dependent activation of the malate-aspartate shuttle by norepinephrine and vasopressin in perfused rat liver. AB - The role of Ca2+ in stimulation of the malate-aspartate shuttle by norepinephrine and vasopressin was studied in perfused rat liver. Shuttle capacity was indexed by measuring the changes in both the rate of production of glucose from sorbitol and the ratio of lactate to pyruvate during the oxidation of ethanol. (T. Sugano et al. (1986) Amer. J. Physiol. 251, E385-E392). Asparagine (0.5 mM), but not alanine (0.5 mM) decreased the ethanol-induced responses. Norepinephrine and vasopressin had no effect on the ethanol-induced responses when the liver was perfused with sorbitol or glycerol. In the presence of 0.25 mM alanine, norepinephrine, vasopressin, and A23187 decreased the ethanol-induced responses that occurred with the increase of flux of Ca2+. In liver perfused with Ca2+-free medium, asparagine also decreased the ethanol-induced responses, but norepinephrine and vasopressin had no effect. Aminooxyacetate inhibited the effects of norepinephrine, A23187, and asparagine. Regardless of the presence or absence of perfusate Ca2+, the combination of glucagon and alanine had no effect on the ethanol-induced responses. Norepinephrine caused a decrease in levels of alpha-ketoglutarate, aspartate, and glutamate in hepatocytes incubated with Ca2+. The present data suggest that the redistribution of cellular Ca2+ may activate the efflux of aspartate from mitochondria in rat liver, resulting in an increase in the capacity of the malate-aspartate shuttle. PMID- 2899419 TI - Sites of action of glucagon and other Ca2+ mobilizing hormones on the malate aspartate cycle. AB - Data from a number of laboratories suggest that the exchange of glutamate for aspartate across the mitochondrial inner membrane is stimulated by glucagon and by Ca2+-mobilizing hormones. The purpose of this study was to determine the site of action of these hormones. Two possibilities were considered and tested. The first hypothesis is that the mitochondrial membrane electrical potential gradient (delta psi m) in the cells is increased by the hormones; and that the putative increase in delta psi m stimulates aspartate efflux. The second possibility is that Ca2+ mediates decreases in cellular levels of alpha-ketoglutarate, secondary to stimulation of alpha-ketoglutarate dehydrogenase, and that the decrease in alpha-ketoglutarate stimulates aspartate production by mitochondria. The effect of glucagon on delta psi m was estimated in intact hepatocytes using the lipophilic cation tetraphenyl phosphonium. No increase in delta psi m was observed due to hormone treatment. On the other hand, alpha-ketoglutarate was found to be an effective competitive inhibitor of aspartate formation via glutamate transamination by isolated liver mitochondria (Ki = 0.55 mM). PMID- 2899420 TI - Nutritional management of patients undergoing long-term antipsychotic and antidepressant therapies. PMID- 2899421 TI - Endocrinological parameters and cell-mediated immunity postoperation for cryptorchidism. AB - Andrological and endocrinological parameters and cell-mediated immunity (CMI) were assessed in 25 postpubertal males who had undergone repair of unilateral or bilateral cryptorchidism in childhood or early adolescence. Among 20 patients with unilateral cryptorchidism, approximately 30% had decreased sperm density, whereas among 5 bilaterally affected, 1 was azoospermic and 2 oligozoospermic. In most patients the motility and viability values were normal, although the percentage of morphologically pathological sperm was higher than normal. Levels of testosterone, dihydrotestosterone, LH, and prolactin were within normal ranges in all the patients. Levels of FSH were slightly elevated. These findings may suggest a better fertility prognosis of postcryptorchid oligozoospermic patients than in patients with oligozoospermia of other etiology. CMI toward autologous semen revealed a positive reaction in 80% of the bilateral group and in 45% of the unilateral group. This response might be due to the damage of seminiferous tubules of undescended testis causing unmasking and exposure of antigenic determinants. PMID- 2899422 TI - Effects of ifenprodil tartrate on alpha-adrenoceptors and Ca2+ movement in isolated canine saphenous veins. AB - The effect of ifenprodil tartrate (IFT) on 2 subtypes of postsynaptic alpha 1- and alpha 2-adrenoceptors was investigated. For this purpose, changes in the tension of isolated canine saphenous veins were measured isometrically, and Ca2+ uptake in these veins was also measured. IFT displaced the dose-contractile response curves for phenylephrine and clonidine in a competitive manner, and the activity sequence of antagonists against phenylephrine was IFT greater than phentolamine greater than prazosin greater than yohimbine. On the other hand, the activity sequence of antagonists against clonidine was IFT greater than phentolamine greater than yohimbine greater than prazosin. The effect of IFT as well as that of phentolamine were different from the other antagonists and of approximately the same specific activities against both agonists. The IFT-induced relaxations of the veins contracted by phenylephrine and clonidine were relatively unchanged in both normal and Ca2+-free solutions. IFT inhibited phenylephrine- and clonidine-induced Ca2+ uptake in the saphenous veins. The results suggest that IFT does not possess a relative selectivity toward postsynaptic alpha 1- and alpha 2-adrenoceptors, and that these actions reflect the vasorelaxing effects on phenylephrine- and clonidine-induced contraction in the canine saphenous veins. PMID- 2899423 TI - Hypoxic stress-induced convulsion and death: protective effect of alpha 2 adrenoceptor and benzodiazepine receptor agonists and Ro 5-4864. AB - Various alpha 2-agonists such as clonidine, guanfacine, B-HT 920 and ICI 106270 were investigated for their effect in hypoxic stress in rats and mice. Pretreatment with alpha 2-adrenoceptor agonists exhibited a yohimbine sensitive antistress effect as they prolonged the latencies for convulsion and death due to hypoxia. Intracerebroventricular administration of clonidine and ICI 106270 also shared the protective effect, indicating the involvement of central alpha 2 adrenoceptors. However, their protective effect, though comparable to diazepam and CL 218872, was more pronounced. The peripheral benzodiazepine receptor agonist, Ro 5-4864, also had a marked antihypoxic stress effect. PMID- 2899424 TI - [Interaction of Entamoeba histolytica and antibodies in situ]. PMID- 2899425 TI - Electroconvulsive treatment compared with lithium in the management of manic states. AB - Thirty-four hospitalized manic patients were randomized to treatment with either lithium carbonate or an average series of nine bilateral electroconvulsive treatments (ECTs), followed by maintenance with lithium carbonate. Weekly ratings of manic, depressive, and psychotic symptoms were obtained for eight weeks, and patients were followed up monthly for up to two years. Ratings by nonblind and blind observers indicated that the patients who underwent ECT improved more during the first eight weeks than did patients who were treated with lithium carbonate. This was especially true of patients with mixed symptoms of mania and depression and/or extreme manic behavior. Clinical ratings after eight weeks showed no significant differences between the lithium carbonate- and ECT-treated patients. Likewise, the two groups had comparable rates of relapse, recurrence, and rehospitalization during the follow-up period. PMID- 2899426 TI - Pheochromocytoma multisystem crisis. A surgical emergency. AB - Three of 27 patients treated for pheochromocytoma between 1974 and 1987 presented with pheochromocytoma multisystem crisis (PMC). This unusual presentation consists of multiple organ system failure, temperature often greater than 40 degrees C, encephalopathy, and hypertension and/or hypotension. Although urgent medical therapy achieved blood pressure control in all three patients, the other manifestations of PMC progressed rapidly in spite of alpha and even beta blockade. The first patient died during attempts to localize a septic focus. The other two patients underwent urgent adrenalectomy and had postoperative improvement in their multiple organ system failure. All three tumors were large and produced markedly elevated levels of epinephrine. In conclusion (1) PMC is an unusual presentation of pheochromocytoma; (2) its manifestations include multiple organ system failure, high fever, encephalopathy, and vascular lability; (3) it may result from increased epinephrine secretion; and (4) successful treatment of PMC demands prompt diagnosis, vigorous medical preparation, and emergency tumor removal if the patient's condition continues to deteriorate. PMID- 2899427 TI - Influence of di-butyltin dilaurate on brain neurotransmitter systems and behavior in rats. AB - Exposure to DBTL (20, 40 or 80 mg/kg body weight) caused a decrease in levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) at all treatment levels. Hypothalamus and frontal cortex appeared to be most affected, since levels of all the three amines examined showed changes in these areas. Maximum decrease of DA was found in corpus striatum, NA in pons medulla and of 5-HT in frontal cortex. These animals also showed a decrease in spontaneous locomotor activity and learning at all the doses. The data indicates involvement of hypothalamus and frontal cortical regions of the brain in the neurotoxicity of DBTL. PMID- 2899428 TI - Gastritis with valproate therapy. AB - We have identified ten children who developed gastritis after prolonged anticonvulsant therapy that included either valproic acid or divalproex sodium. Presenting symptoms were primarily feeding difficulties, including anorexia and refusal to eat. Vomiting was present in two thirds of the patients, with diarrhea, weight loss, and abdominal pain occurring less frequently. Occult blood in stool samples was a late development. All patients responded to therapy with H2-receptor antagonists, oral antacids, or both, with prolonged treatment often necessary to prevent relapse. Although gastrointestinal tract side effects are common with the initiation of valproate sodium therapy, feeding difficulties after long-term treatment are less common. Gastritis should be suspected in children receiving valproate therapy when feeding difficulties arise, particularly if the symptoms are persistent or recurrent. PMID- 2899429 TI - Inhibitory effect of somatostatin on the basal and TSH-stimulated 3H-thymidine incorporation into rat thyroid lobes incubated in vitro. AB - The effects of somatostatin on the spontaneous and TSH--stimulated incorporation of tritiated thymidine into the rat thyroid lobes incubated in vitro were investigated. The rate of 3H-thymidine incorporation was used as an index of thyroid follicular cells (TFC) proliferation. It was shown that: 1) somatostatin, at a concentration of 10(-7)M, decreased 3H-thymidine incorporation into DNA of TFC, 2) the highest somatostatin concentration, as tested in this study (10( 6)M), produced a similar decreasing effect; the decrease, in this case, did not attain significance vs. controls, 3) somatostatin, when employed together with TSH, suppressed the stimulatory effect of the latter hormone on 3H-thymidine incorporation into DNA of thyroid lobes. PMID- 2899430 TI - Toxicity of polycyclic aromatic hydrocarbons. IV. Effects of diphenaldehyde, a major product of ozonized phenanthrene, in rats. AB - Diphenaldehyde is the major product of phenanthrene ozonized on silica gel. Male Sprague-Dawley rats were treated with a single ip injection of DMSO (3.0 ml/kg) or diphenaldehyde (90 mg/kg) in DMSO. Diphenaldehyde produced significant alterations in levels of serum aspartate aminotransferase, alanine aminotransferase, sorbitol dehydrogenase, gamma-glutamyl transpeptidase, and lactate dehydrogenase relative to DMSO-injected rats 24 hr after injection. These results, as well as gross observations on necropsy, suggest that diphenaldehyde exhibits significant hepatotoxicity. PMID- 2899431 TI - Effects of drugs on the activity of histamine-N-methyltransferase from guinea pig skin. PMID- 2899432 TI - Stimulatory effect of angiotensin II on the electric properties of the isolated toad skin. AB - In 1982 we showed that angiotensin II (Agt II) stimulates the bioelectric properties of the isolated toad skin and that this effect is blocked by pretreatment of the skin with indomethacine [J. B. Concha et al., IRCS Med. Sci. 10, 584 (1982)]. Ussing's technique and several inhibitors were used to continue this study on the isolated Pleurodema thaul skin. Serosal Agt II produced a dose dependent increase in electrical parameters: a maximal concentration of 6 X 10( 6) M Agt II increased potential difference by 43 +/- 7.8% and short-circuit current by 51.5 +/- 7.7%. The responses were not affected by either alpha or beta blockers or by atropine. Indomethacine blocked responses to the calcium ionophore A23187 and to Agt II which were similar to each other. Additive effects of Agt II and of the calcium ionophore A23187 were found. No response to Agt II was obtained when Ca2+-free Ringer was used on the serosal side. Calcium channel blockers (nifedipine, verapamil, manganese), pentobarbitone and saralasin blocked the response to Agt II. This pharmacological evidence is in favour of the hypothesis that Agt II activates specific membrane receptors, leading to Ca2+ release and formation of prostaglandins which stimulate adenyl cyclase. This increases cAMP secretion, which in turn increases apical membrane permeability to sodium and enhances the active transport system. PMID- 2899433 TI - In vitro studies on the interaction of famotidine with liver microsomal cytochrome P-450. PMID- 2899434 TI - Beta-2-agonists of third generation. AB - Beta-adrenergic agents have been used for a long time in the treatment of asthma. For the purpose of bronchodilation the better results would be attained with the increase in Beta-2-selectivity. From the newer Beta-agonists the mot currently used are TERBUTALINE, FENOTEROL, SALBUTAMOL, CLEMBUTEROL, TOLBUTEROL, CARBUTEROL, PROCATEROL, RIMITEROL and REPROTEROL, this last combining in its molecule the structure of a beta-agonist with a Xanthine group. These agents could be used in different ways, by mouth, injection and inhalation (with a exception of Clembuterol which is effective only by oral route). The authors have, some years ago, comparatively studied the bronchodilating effect of Salbutamol and Fenoterol including 18 patients. The main increase of PFR was slightly higher after FENOTEROL but this difference was not significant. The authors have studied REPROTEROL by inhalation and oral routes in 11 asthmatic patients. After inhalation of 400 mcg of REPROTEROL the bronchodilator effect was comparable to others inhaled bronchodilators. However they could not confirm that REPROTEROL acts also as a Xanthine and only traces of Theophylline have been detected in blood of subjects taking it. These data seem to indicate that REPROTEROL do not release Theophylline in the body or only release a Xanthine like compound not detected by "EMIT" of high pressure liquid chromatography. PMID- 2899435 TI - [Treatment of chronic urticaria with ketotifen]. AB - Ketotifen, an inhibitor of the mastocytes degranulation is used in the treatment of allergic asthma. The use of this drug in chronic urticaria is proposed because histamine play a major role in the production of the lesions. In this study, 36 patients with chronic urticaria of various aetiology are treated with ketotifen (2 mg/d). 12 patients were healed, 11 good results and 12 failure were obtained. The best results are obtained in cold urticaria and in food related urticaria. This result were compared with data concerning the treatment of chronic urticaria. PMID- 2899436 TI - Influence of acute ethanol administration on hepatic glutathione metabolism in the rat. AB - The effect of acute ethanol administration on the hepatic metabolism of glutathione was studied in male Wistar rats. Animals fasted for 18 hr received ethanol (5 g/kg body wt.) through a gastric tube as a 20% (w/v) solution in 0.154 NaCl. Four hours after administration of ethanol liver glutathione content was decreased by 21% when compared to saline-treated controls. A significant reduction (28%) was also found in gamma-glutamylcysteine synthetase activity and plasma glutathione levels were increased non significantly by 17% with respect to control rats. Glutathione S-transferase activity in the liver of ethanol-treated animals was decreased by 28% but no change was found in total glutathione peroxidase activity. The results indicate that the lowered glutathione synthesis could be an important factor contributing to the reduction of hepatic glutathione concentration following the acute ingestion of ethanol. PMID- 2899437 TI - gamma-Glutamyltransferase: normal cortical levels in Alzheimer disease. AB - gamma-Glutamyltransferase (EC 2.3.2.2; gamma-GT) may be important in the transport of amino acids or peptides across the blood-brain barrier. Gamma-GT activities were the same in cortical samples from Alzheimer and age-matched control brains, and there was no correlation between gamma-GT and choline acetyltransferase (ChAT) or acetylcholinesterase (AChE) levels, both of which were significantly reduced in the Alzheimer samples. ChAT and AChE activities were significantly correlated in both groups. ChAT showed a negative correlation with age in the controls and a positive correlation in the Alzheimer group. The opposite was true for gamma-GT, although the correlations were of low significance. The results do not lend any support to the hypothesis of a defect in the blood-brain barrier in Alzheimer disease. PMID- 2899438 TI - In vitro susceptibility of diarrhoea producing gram negative enteric bacteria to sulfasalazine, 5-aminosalicylic acid, sulfapyridine and four quinolones. Brief report. AB - The in vitro susceptibility of diarrhoea producing Gram negative enteric bacteria to sulfasalazine, 5-aminosalicylic acid, sulfapyridine and four quinolones was investigated using an agar dilution method. All strains were resistant to 1600 micrograms/ml of sulfasalazine and 5-aminosalicylic acid. MIC range of sulfapyridine for Y. enterocolitica was 3.1-25 micrograms/ml (median:6.2) and for Salmonella 25-100 micrograms/ml (median: 100) Campylobacter jejuni/coli were less susceptible to sulfapyridine with MIC values ranging from 200 to 800 micrograms/ml. Shigella and three of five E. coli strains were resistant to 1600 micrograms/ml of sulfapyridine. Two strains of E. coli were inhibited by 25 micrograms/ml. All strains were fairly susceptible to enoxacin, ciprofloxacin, pefloxacin and ofloxacin. Cirpofloxacin was the most active drug on weight basis. PMID- 2899439 TI - Importance of ancillary properties of beta blockers in angina: a study of celiprolol and atenolol. AB - Celiprolol (400 mg) and atenolol (100 mg) were given once a day to 16 patients with stable angina pectoris in a double blind placebo controlled crossover study. Celiprolol produced less suppression of heart rate both at rest and during exercise than atenolol. Both drugs were equally effective in reducing the frequency of angina and in delaying the onset of ischaemia during exercise. Radionuclide ventriculography showed that atenolol but not celiprolol lowered cardiac output at rest and during exercise. Thus the ancillary properties of celiprolol, including partial beta 2 agonist activity and direct vasodilating activity, have detectable effects on cardiac function that may be beneficial in patients with angina. PMID- 2899440 TI - Depression of early phase of HTLV-I infection in vitro mediated by human beta interferon. AB - Natural human interferon beta (beta-IFN) was tested during the early phase of in vitro infection with HTLV-I virus of human cord blood mononuclear cells (CBL), to evaluate whether its antiviral and immunomodulating effects might prevent spreading of infection in the host. beta-IFN was found to reduce HTLV-I transmission and integration in CBL cultures. Moreover, beta-IFN had no effect in preventing virus transmission and integration in K562 and a very limited effect in HL60 and Molt-4 human tumour lines, suggesting a cell-type specific mode of action. beta-IFN induced a 'priming' response on CBL, since overnight pretreatment of recipient cells or one single treatment at the onset of the coculture were almost equally effective in protecting against HTLV-I infection. During the early days post infection (p.i.), IFN-treated CBL showed a pattern of phenotypic markers that was closer to that of non-infected CBL. In contrast, untreated CBL exposed to HTLV-I showed a percent increase of Tac+, M3+ and Leu 11+ subpopulations. Cell-mediated immune responses of CBL were depressed after coculturing with HTLV-I producer MT-2 cells. beta-IFN was able to boost the cell mediated cytotoxicity of fresh and infected CBL against both K562 and MT-2 target cells. Leukocyte blastogenesis in mixed lymphocyte/tumour cell cultures, evaluated in terms of 3H-thymidine incorporation during the first week p.i., was also enhanced by IFN when macrophages and lymphocytes were reconstituted at an optimal 1:20 ratio. It is conceivable that this overall enhancement of the immune response induced by beta-IFN could contribute to reduce HTLV-I infection in vitro. PMID- 2899441 TI - Inactivation of the F1-ATPase from the thermophilic bacterium PS3 by 5'-p fluorosulfonylbenzoylinosine at 65 degrees C is accompanied by modification of beta-tyrosine-364. AB - A major radioactive peptide, T1, was resolved by high-performance liquid chromatography from a tryptic digest prepared from the F1-ATPase from the thermophilic bacterium PS3 which had been inactivated with p fluorosulfonylbenzoyl[3H]inosine. Two radioactive peptides, T1P1 and T1P2, were isolated from a peptic digest of T1 by high-performance liquid chromatography. The sequences of T1P1 and T1P2 were shown to be E-E-H-X-Q-V-A-R and E-E-H-X-Q, respectively, where X corresponds to derivatized Tyr-364 of the beta subunit. PMID- 2899442 TI - Mechanism of multidrug resistance. PMID- 2899444 TI - Almitrine as a long term treatment for chronic obstructive pulmonary disease. PMID- 2899443 TI - [Changes in the activity of adenylate- and guanylate cyclase in different rat tissues after chronic administration of ACTH or cortisol]. AB - The state of adenylate and guanylate cyclases in the adrenals, suprarenal fat and ventricular myocardium of the rat was studied under conditions of chronic administration of ACTH or cortisol. By the end of ACTH injections the weight of the adrenals and the DNA content in them increased 6 and 3 times, respectively; both parameters showed a gradual increase. The corticosteroid level in the blood changed throughout the experiment. The changes in the DNA content in the adrenals and in the corticosteroid level in the blood were oppositely directed. This was paralleled with cyclic changes in the basal and stimulated activities of adenylate and guanylate cyclases occurring with a periodicity of 15 days. The peaks of the cyclase activity preceded the increase in the DNA content. Similar cyclic changes in the enzyme activity were observed in the adipose tissue and myocardium. It was supposed that periodic changes in the cyclase activity are the main prerequisites for the growth and replication of cells under conditions of changed hormonal status of the organism. PMID- 2899445 TI - Effects of enalapril on changes in cardiac output and organ vascular resistances induced by alpha 1- and alpha 2-adrenoceptor agonists in pithed normotensive rats. AB - 1. Cardiac output, its distribution and regional vascular resistances were determined with tracer microspheres in pithed rats in the presence of the angiotensin converting enzyme inhibitor enalapril. The effects of enalapril on the cardiovascular responses elicited by either the alpha 1-adrenoceptor agonist phenylephrine or the alpha 2-adrenoceptor agonist xylazine were determined. 2. Enalapril decreased diastolic and mean blood pressure by decreasing cardiac index and total peripheral resistance. It induced vasodilatation in the kidney, epididimides, epididimidal fat and pancreas/mesentery. Vasoconstriction in the lungs, testes and liver was evident following enalapril administration as well as a decrease in the proportion of cardiac output passing to them, whilst the pancreas and mesentery received a greater proportion of the cardiac output. All the above effects of enalapril were reversed by infusion of angiotensin II at a rate of 75 ng kg-1 min-1. 3. Xylazine increased blood pressure by increasing both cardiac output and total peripheral resistance. Enalapril did not affect the increase in cardiac output caused by xylazine but decreased the effect of the alpha 2-agonist on blood pressure by preventing the increase in total peripheral resistance. Inhibition by enalapril of xylazine-induced vasoconstriction in the kidneys, testes, fat and gastrointestinal tract contributed to the decrease in total peripheral resistance. Enalapril also inhibited xylazine-induced changes in cardiac output distribution to the liver, lungs and heart. All the above effects of enalapril were reversed by infusion of angiotensin II. 4. Enalapril decreased the sustained phase of the pressor response to an infusion of phenylephrine whilst having no effect on the initial peak pressor response to a bolus injection of phenylephrine. Phenylephrine increased both cardiac output and total peripheral resistance and enalapril abolished its effect on total peripheral resistance whilst having no effect on the increase in cardiac output. Enalapril inhibited phenylephrine-induced vasoconstriction in the testes, fat, muscle, spleen and gastrointestinal tract. Enalapril also inhibited phenylephrine-induced changes in cardiac output distribution to the lungs and liver. The infusion of angiotensin II did not fully reverse the inhibitory effect of enalapril either on the phenylephrine-induced increases in diastolic blood pressure or on the vasoconstriction in the fat, spleen and gastrointestinal tract, but did reverse all other effects of enalapril. PMID- 2899446 TI - Somatosensory neurons in partially deafferented rat hindlimb granular cortex subsequent to transection of the sciatic nerve: effects of glutamate and acetylcholine. AB - The effects of drugs administered iontophoretically were studied on 302 neurons isolated from partially deafferented hindlimb granular cortex of the rat and were compared to a previously studied sample from normal granular cortex. The proportions of cells affected by glutamate and acetylcholine (ACh) were not markedly different after partial deafferentation, but the cells were more readily depolarized by glutamate and their responses to a fixed dose of glutamate were larger. Fewer cells were excited strongly by ACh (up to the point of depolarization block) and the amplitudes of responses to test pulses of ACh were reduced in infragranular layers after partial deafferentation. Fifteen cells (5.9%) were inhibited by ACh administration, whereas in normal cortex this value was less than 1%. Fewer receptive fields were uncovered by glutamate after partial deafferentation, but more receptive fields were enlarged by this substance after nerve transection. These data were interpreted to mean that the cells from deafferented cortex had fewer excitatory inputs and as well, were apparently under a comparatively weaker degree of inhibitory control after deafferentation. The administration of ACh uncovered fewer somatic inputs than in normal animals. Responses were enhanced by ACh less frequently, and repeated treatments with ACh often led to a reduction in the effectiveness of the afferent stimulus. Increases in neuronal thresholds for somatic stimuli also were observed. The laminar distribution of the effects of ACh was similar to the distribution observed in normal animals. The responses to iontophoretically administered ACh and its agonists appeared to be mediated through both nicotinic and muscarinic receptor processes after partial deafferentation. Often the time course of the effects of ACh was abnormal, being characterized by oscillations between silence and very high rates of discharge with a period of 6-12 s. These observations are consistent with the hypothesis that after a major deafferentation (i) there is a reduction of the inhibitory controls normally present in the somatosensory cortex, and (ii) neuronal responses to ACh are modified in partially deafferented cortex. The magnitude of the responses of cells to ACh in the supragranular layers are larger after deafferentation whereas the magnitude of responses in the infragranular layers are reduced by this procedure. These changes may be related to changes induced by deafferentation in the distribution of receptors and/or in their pharmacological properties. PMID- 2899447 TI - The dopaminergic innervation of monkey prefrontal cortex: a tyrosine hydroxylase immunohistochemical study. AB - The distribution of tyrosine hydroxylase (TH)-immunoreactive fibers was characterized immunohistochemically in the prefrontal cortical regions of both Old World cynomolgus monkeys (Macaca fascicularis) and New World squirrel monkeys (Saimiri sciureus). In both species, differences in the density and/or laminar distribution of TH-labeled fibers were detected both across and within almost every prefrontal cytoarchitectonic region. In cynomolgus monkeys, areas 9 and 24 had the greatest density of TH-labeled fibers, areas 11, 12, 13 and 25 were of intermediate density, and areas 10 and 46 had the lowest density of immunoreactive fibers. Differences in fiber density within many of these regions were also consistently observed. On a laminar basis, the distribution of labeled fibers in a given area of cynomolgus prefrontal cortex was systematically related to the overall fiber density of that area. For example, in the lightly innervated fundus of the principal sulcus (area 46), labeled fibers were primarily present in layer I and layers V-VI, whereas in area 9, the most densely innervated region, TH-labeled fibers were present in all cortical layers. Similar regional differences in the density and laminar distribution of TH-immunoreactive fibers were also present in squirrel monkey prefrontal cortex. In previous studies, we have analyzed the regional and laminar distributions of fibers immunoreactive for TH and dopamine-beta-hydroxylase (DBH), a specific marker for noradrenergic cortical fibers, in multiple areas of cortex from both normal and locus ceruleus lesioned animals. These comparisons, which have been confirmed in the present report, indicate that anti-TH and anti-DBH label distinct populations of axons in monkey neocortex, which presumably are dopaminergic and noradrenergic, respectively. Thus, the distribution of TH immunoreactivity described in the present report suggests that dopaminergic fibers are distributed in a very heterogeneous fashion in monkey prefrontal cortex. The distinctive innervation patterns exhibited by these fibers reveal the regions and layers that may be the principle sites of action of dopamine in exerting its effects on prefrontal cortical function. PMID- 2899448 TI - Levels of neurotransmitter and cytoskeletal protein mRNAs during nerve regeneration in sympathetic ganglia. AB - The present study examines levels of neurotransmitter messenger RNA (mRNA) at various stages after crush of postganglionic nerves in the superior cervical ganglia. Using complementary DNA (cDNA) probes, we demonstrated a reduction in ganglionic mRNA levels for tyrosine hydroxylase (TH) after axotomy. Concomitantly, actin and tubulin mRNA levels in ganglia were increased. Thus, in neurons of sympathetic ganglia, axotomy appears to be associated with a selective reduction in levels of TH mRNA, and, in turn, alters levels of protein and enzyme activities. PMID- 2899449 TI - Characterization of opioid binding sites in murine neuroblastoma. AB - The binding of [3H] [D-Ala2, MePhe4, Gly-ol5]enkephalin ([3H]DAGO), [3H]D-Ala2,D Leu5]enkephalin ([3H]DADLE) and (+/-)-[3H]ethylketocyclazocine ([3H]EKC) to neurotumor tissues derived from S20Y neuroblastoma cells transplanted into A/Jax mice was examined. Specific and saturable binding to [3H]DADLE and [3H]EKC was detected, and the data fit a single homogeneous binding site for each ligand. Scatchard analysis for [3H]DADLE and [3H]EKC yielded Kd values of 0.65 and 0.45 nM, respectively, and Bmax values of 9.2 and 116 fmol/mg protein. Binding was dependent on time, temperature, and pH, and was sensitive to Na+ and guanine nucleotides. Pretreatment of the tumor homogenates with trypsin markedly reduced binding to both ligands, suggesting that the binding sites were proteinaceous in character. Displacement experiments indicated that delta (delta) receptor related compounds (e.g. DPDPE, ICI 174,864) avidly displaced [3H]DADLE, whereas kappa (kappa) related compounds (e.g. U50,488, dynorphin) markedly competed with [3H]EKC. Mu (mu) receptor drugs (e.g. DAGO, beta-FNA, morphine) were not potent in displacing either [3H]DADLE or [3H]EKC. These results are the first to characterize opioid binding sites in tumor tissue. The function of these sites is unclear, but previous evidence as to the growth regulatory properties of endogenous opioid systems may suggest that either one, or both, binding sites may be involved in carcinogenic events. PMID- 2899450 TI - Enhancement of opioid cataleptic response by cortical frontal deafferentation or intrastriatal injection of NMDA-receptor antagonists. AB - The cataleptic activity of morphine and methadone was markedly potentiated in frontally decorticated rats with no apparent changes in the onset or duration of action. Enhancement of the opioid cataleptic response was not due to changes in the availability of the drugs in the brain. The potentiation of methadone-induced catalepsy in decorticated rats was mimicked in naive rats by intrastriatal (i.s.) application of 2-amino-7-phosphonoheptanoic acid (AP7), a potent and selective antagonist of N-methyl-D-aspartate (NMDA) receptors. Therefore, degeneration of glutamatergic synapses following decortication could be responsible for the changes in behavioral effects caused by opioids. The failure of AP7 to elicit an effect after injection into the n. accumbens fits with the possibility of a selective involvement of the striatum in this phenomenon. That the striatum plays a critical role in the expression of opioid-induced catalepsy was substantiated by the findings that: (1) naloxone, an opioid antagonist, injected i.s., prevents the potentiation of catalepsy induced by methadone and morphine in decorticated animals, (2) oxotremorine, a muscarinic agonist, injected i.s., reverses the enhancement of opioid-catalepsy in decorticated rats, (3) earlier studies by others showed that ablation of the striatum had a facilitatory action on opioid induced catalepsy. In conclusion, evidence is given that the corticostriatal pathway exerts an inhibitory effect upon narcotic-induced cataleptic behavior. The possibility that this effect is mediated through striatonigral GABAergic output is discussed. The data further suggest that the neuronal mechanisms through which the corticostriatal pathway mediates narcotic catalepsy is operative through activation of NMDA receptors within the striatum. PMID- 2899451 TI - Esmolol in the treatment of supraventricular tachyarrhythmias. AB - Infusion of esmolol, an ultra short acting beta-blocker was used in the acute management of 48 patients with supraventricular tachyarrhythmias. Following acute control of the heart rate, patients received maintenance of esmolol infusion for 6 h when they were transferred to alternate oral antiarrhythmic agents. Prompt control of heart rate (mean +/- SD, 15 +/- 8.8 mins) was achieved in 85% of patients with esmolol at a dose rate of 80 +/- 59 micrograms/kg/min. Ninety percent of these subjects were successfully transferred to alternate oral therapy. Five subjects experienced transient side effects. Esmolol was highly effective and particularly suitable for the acute management of patients with supraventricular tachyarrhythmias. PMID- 2899452 TI - Common sports injuries to the foot and leg. AB - Running related injuries to the leg and foot account for approximately 45 per cent of the total injuries to the lower extremity. The incidence of running injuries has increased significantly in the past decade, thus, creating a demand for increased proficiency in treating runners. Specifically, overuse injuries account for most of the runner's complaints. The goal of sports medicine as mentioned previously is to keep the athlete active and injury free. To achieve this goal the etiologies of the injuries must be recognized and treated. Common, preventable causes of overuse injuries would include training errors and biomechanical factors. The biomechanical factors as they relate to foot and leg have been addressed within this article. Early recognition and biomechanical treatment will decrease the vast majority of the lower limb injuries. PMID- 2899453 TI - Presence of HTLV-I proviral DNA in patients with adult T-cell leukemia/lymphoma in Taiwan. AB - Human T-lymphotropic virus-I (HTLV-I) proviral DNA was demonstrated in the leukemic cells of two newly identified cases of adult T-cell leukemia/lymphoma (ATL) in Taiwan by the Southern blot hybridization method. Therefore, the ATL cases diagnosed clinicopathologically in Taiwan were, for the first time, documented to be definitely related to HTLV-I. PMID- 2899454 TI - Amino acids modulate calcium permeability of the plasma membrane of human neuroblastoma cells. AB - Four different amino acids (kainate, N-methyl-D-aspartate, L-cysteine sulfinate and D,L-2-amino-5-phosphonovalerate) have been observed to stimulate uptake of 45Ca2+ into human neuroblastoma cells. This stimulation of uptake is specific and many amino acids which are structural analogs of the above compounds are without activity. The calcium movement is not inhibited by compounds which block voltage dependent calcium channels. Biological specificity is observed in which some cell lines respond to the amino acids and others do not. It is concluded that these amino acids are acting on a class of receptors whose physiological role is modulation of neuronal metabolism by modulating the calcium permeability of the plasma membrane. The amino acids can substitute for the, as yet, unidentified natural agonists, albeit with low affinity. PMID- 2899455 TI - Properties of verapamil-hypersensitive multidrug-resistant Chinese hamster ovary cells. AB - Two vincristine-resistant Chinese hamster ovary cell lines have been shown previously to be hypersensitive to the calcium channel blocker, verapamil. They are now shown to be hypersensitive to the membrane-active agent quinidine sulfate and to the calcium channel blockers diltiazem and nicardipine. Hypersensitivity to quinidine sulfate implies that calcium channels are not the primary target for these drug effects on these cell lines and is consistent with our previous observation that their calcium accumulation is normal in the presence and absence of verapamil. The two cell lines have elevated levels of membrane P-glycoprotein and of two cytosolic proteins, Mr 27,000 and pI 6.0 and 6.4. Revertants have normal levels of these cytosolic proteins, suggesting that these proteins may play a role in conferring resistance. [3H]Verapamil accumulation by the two cell lines is lower than in controls. One of the cell lines has been hybridized to normal cells and the vincristine resistance and verapamil sensitivity of three hybrid clones has been determined. Vincristine resistance is semidominant but verapamil hypersensitivity is completely recessive. PMID- 2899456 TI - Apparent stronger expression in the human adrenal cortex than in the human adrenal medulla of Mr 170,000-180,000 P-glycoprotein. AB - A monoclonal antibody (MAb), MRK 16, specific to Adriamycin-resistant human myelogenous leukemia cell line K562, was used to examine whether the antigen molecules (P-glycoprotein) recognized by the MAb are present in the adrenals. The materials examined included 61 human adrenals and several cell lines. Immunohistochemical analysis revealed that almost all of the human adrenal specimens (59 out of 61) were stained positively with MAb MRK 16 and that the antigen was strongly expressed even in cases where anticancer agents had not been given. Immunoprecipitation showed that the Mr 170,000-180,000 glycoprotein was present in all of the adult adrenals but not in fetal and neonatal adrenals. Furthermore, fluorescence image analysis revealed that the P-glycoprotein was more strongly expressed in the cortex than in the medulla, showing a tendency to occur in cell clusters in the latter area. The cell lines derived from animal adrenals (SW-13, Y-1, and PC-12) showed no positive staining with MAb MRK 16. It is suggested that this glycoprotein may be related to maturation of the adrenal, in which it possibly plays a physiological role. PMID- 2899457 TI - Contrasting actions of staurosporine, a protein kinase C inhibitor, on human neutrophils and primary mouse epidermal cells. AB - Staurosporine, a recently described microbial alkaloid, is uniquely potent as an inhibitor of protein kinase C in vitro, being active at nM concentrations rather than the microM concentrations typical of other inhibitor classes. Like these other inhibitors, however, staurosporine exhibits only limited selectivity among different protein kinases. We report here that, in intact human neutrophils, nM concentrations of staurosporine blocked the action of the phorbol ester tumor promoters. In mouse primary epidermal cells, on the other hand, staurosporine failed to block the effects of phorbol 12,13-dibutyrate on epidermal growth factor binding and on induction of ornithine decarboxylase and epidermal transglutaminase. Unexpectedly, staurosporine induced morphological changes in keratinocytes to a dendritic shape resembling that induced by the phorbol esters. It also induced epidermal transglutaminase and cornified envelope production, markers of the differentiative pathway in the epidermal cells. We conclude that the effectiveness of staurosporine as a protein kinase C inhibitor in intact cells may depend markedly on the cell system. Other actions of staurosporine may predominate, and, in keratinocytes, its activity is suggestive of a tumor promoter rather than of an inhibitor of tumor promotion. PMID- 2899458 TI - Partial inhibition of the growth of transplanted dunning rat prostate tumors with the long-acting somatostatin analogue sandostatin (SMS 201-995). AB - The growth-inhibiting effects of the long-acting somatostatin analogue Sandostatin on the transplanted Dunning R3327-H androgen-sensitive rat prostate tumor were investigated. Recipient animals were male Copenhagen x Fischer F1 rats (N = 36). When mean tumor volume reached 700 mm3 (20 weeks following transplantation), the rats were divided into four groups: control; Sandostatin (100 micrograms/kg s.c. twice a day); castrate; castrate/Sandostatin. Tumor size was assessed by magnetic resonance imaging 21, 42, 63, 105, and 138 days subsequently. Administration of Sandostatin was interrupted between days 43 and 62. As assessed by transplant volume, Sandostatin caused a moderate (up to 50%) but highly significant (P less than 0.001) suppression of tumor growth in the intact rats; the effect was reversed when drug administration was stopped. In the castrates, in which tumor growth was markedly less than in intact rats, no significant effect of Sandostatin was seen. Analysis of the tumor growth rate demonstrated that Sandostatin led to a 19% reduction (P less than 0.05) in growth rate in intact rats and a 9% decrease (not significant) in castrates. These findings extend previous reports of partial suppression of various types of tumors in vivo with Sandostatin and other somatostatin analogues. Their relevance with regard to the possible use of Sandostatin in the treatment of prostatic carcinoma in humans is discussed. PMID- 2899460 TI - [Incidence and clinical forms of hemorrhagic fever with renal syndrome in Eastern Slovakia]. PMID- 2899459 TI - [Celiprolol tolerance in patients with left ventricular function disorders]. PMID- 2899461 TI - Certain beta-blockers can decrease beta-adrenergic receptor number: I. Acute reduction in receptor number by tertatolol and bopindolol. AB - We have previously reported that a potent new beta-blocker, tertatolol, when given at therapeutic doses to healthy volunteers, rapidly reduced the number of human mononuclear leukocyte beta-receptors. In the present study, the mechanism of receptor regulation by beta-antagonists incubated with target cells in vitro was investigated. Two different cell types (human mononuclear leukocytes and S49 murine lymphoma cells) were used, and beta-adrenergic receptors were measured using either the hydrophilic ligand 3H-CGP 12177 (specific for surface receptors) or lipophilic 125I-pindolol (which measures total receptors). In a comparison between beta-blockers, tertatolol and bopindolol, but not propranolol and pindolol, were found to rapidly (1 hour at 37 degrees C) reduce the number of beta-adrenergic receptors. This was paralleled by a reduction in isoproterenol stimulated cyclic AMP accumulation. The reduction in receptors was the same whether surface or total receptors were measured; thus, it was not due to receptor sequestration. This effect was not caused by partial agonist activity (bopindolol is a weak partial agonist); in parallel experiments, tertatolol and bopindolol, but not pindolol (potent partial agonist) and isoproterenol (full agonist), reduced beta-adrenergic receptors. Finally, this effect was not due to irreversible binding: the receptor reduction induced by the irreversible blocker bromo-acetyl-alprenolol-methane (BAAM) was stable for several hours, while the effect of tertatolol and bopindolol was slowly reversed over the same time course. We suggest that tertatolol and bopindolol have two effects on beta adrenergic receptors: they bind competitively, and then they modify the receptors so that they are no longer available for binding by ligands or catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899462 TI - Certain beta-blockers can decrease beta-adrenergic receptor number: II. Down regulation of receptor number by alprenolol and propranolol in cultured lymphoma and muscle cells. AB - We have used two different cultured cell lines--S49 lymphoma cells and BC3H-1 muscle cells--to examine the regulation of beta-adrenergic receptors by receptor antagonists. Rather than an increase ("up-regulation") of receptor number that such antagonists often produce, we found that certain beta-blockers elicit a decrease ("down-regulation") of beta-adrenergic receptors. Alprenolol and propranolol, but not sotalol or ICI 118,551, at concentrations of 10-100 nM down regulated beta-adrenergic receptors 20-70% following 16-20 hours of treatment of S49 or BC3H-1 cells. Several observations suggest that this phenomenon depends upon beta-receptor interaction, including stereoselectivity [(-)-enantiomers more potent than (+)-enantiomers], blockade of the effect by ICI 118,551, absence of down-regulation of alpha-adrenergic receptors in BC3H-1 cells, and lack of a decrease in beta-adrenergic receptor-independent (forskolin-stimulated) cyclic AMP accumulation in S49 cells. The possibility of retained antagonist interfering with receptor measurement was precluded by the fact that the antagonist-induced decrease in receptor number required several hours incubation and occurred without a prominent change in receptor affinity. The ability of the beta-blockers to elicit down-regulation did not correlate with hydrophobicity of the drugs. Antagonist-induced down regulation of beta-adrenergic receptors did not occur in S49 lymphoma cells that lack the alpha-subunit of Gs, the guanine nucleotide binding regulatory protein, thus implying a requirement for receptor-alpha s interaction in eliciting beta-receptor down-regulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899463 TI - Neurohumoral responses to chronic myocardial infarction in rats. AB - In chronic cardiac failure, various neurohumoral mechanisms are activated to sustain blood volume, blood pressure, and organ perfusion. Using the coronary artery ligation model of heart failure in the rat, we have measured changes in vasoactive hormone secretion and related these changes to salt and water status during a 1-month period. When compared with controls, rats with infarction had a marked rise in plasma atrial natriuretic peptide (294 +/- 59 vs. 79 +/- 10 pg/ml, p less than 0.001) although there was no increase in total exchangeable body sodium. Plasma renin activity and plasma aldosterone concentrations were the same for both rats with infarction and controls. Similarly, there were no significant differences in plasma arginine vasopressin, plasma osmolality, or plasma sodium concentration in rats with infarction. Ventricular norepinephrine levels were reduced in animals with infarction (p less than 0.01). Plasma atrial natriuretic peptide levels were raised in this model of chronic left ventricular failure. However, there was no salt retention and little stimulation of the renin angiotensin-aldosterone system or vasopressin. The results suggest that high circulating atrial natriuretic peptide levels may prevent or limit salt and water retention, either directly or indirectly, by inhibiting the renin-angiotensin aldosterone system. PMID- 2899464 TI - The rate of loss of CR1 from ageing erythrocytes in vivo in normal subjects and SLE patients: no correlation with structural or numerical polymorphisms. AB - The stability of CR1 (complement receptor type 1) on ageing erythrocytes in vivo was examined in a group of normal subjects who had been genotyped using a restriction fragment length polymorphism (detected using a cDNA probe for CR1) that correlates with the numerical expression of CR1 on normal erythrocytes (H = allele correlating with high expression, L = low). Erythrocytes were separated into 5 fractions of increasing age on discontinuous Percoll gradients. Mean CR1 numbers on erythrocytes fell from 636 molecules per cell in the first fraction to 384 in the fifth in the HH group and from 478 to 315 in the LL group. There was no difference in the rate of decline of CR1 numbers between the groups. A group of nine SLE patients was also studied in the same way; their genotypes were HH (four) and HL (five). Mean CR1 numbers amongst all of these patients fell from 477 to 232, a faster rate of decline than in a genotypically matched group of normal subjects. There was no difference in the prevalence of the different structural allotypes amongst 30 SLE patients compared with 21 normal subjects. These data provide further evidence that there are enhanced extracellular mechanisms for the removal of CR1 from erythrocytes of SLE patients and do not support the hypothesis that inherited variation in CR1 expression on erythrocytes increases disease susceptibility to SLE. PMID- 2899465 TI - Isocitrate dehydrogenase in D. melanogaster imaginal discs: pattern development and alteration by homoeotic mutant genes. AB - The distribution of the soluble form of NADP+-dependent isocitrate dehydrogenase (ICDH) was examined in Drosophila melanogaster imaginal discs. Development of the enzyme patterns and the specific transformations of the patterns by homoeotic mutants were studied. ICDH pattern formation was followed in eye-antennal discs and wing discs from the late 2nd instar stage through 3rd instar and 8 hours into prepupal development. The patterns formed gradually in both disc types. The most interesting pattern developed in the eye portion of the eye-antennal disc complex. ICDH distribution as well as staining intensity correlated well with differentiation of the ommatidia. The spatial distribution of ICDH within the discs was under genetic control. The patterns reflected the state of determination of the disc. When the presumptive tissue type was transformed via mutant homoeotic genes to different determinative states, the ICDH pattern likewise transformed to the pattern characteristic of the newly acquired structure. PMID- 2899466 TI - Reliability of QT intervals as indicators of clinical hypercalcemia. AB - Reliability of corrected QT intervals (QoTc, QaTc, and QeTc) as indicators of clinical hypercalcemia was assessed in 14 hypercalcemic patients. Hypercalcemia was severe to extreme (serum calcium 14.9 to 22.8 mg/dl) in 11, moderate (13.4 mg/dl) in 1, and mild (12.2 and 11.8 mg/dl) in 2 patients. QT intervals during hypercalcemia were compared with those during normocalcemia either before or after development of hypercalcemia. QeTc interval showed neither significant correlation with serum calcium nor any consistent pattern of change with development of hypercalcemia or normalization of serum calcium. In contrast, QoTc and QaTc intervals shortened with development of hypercalcemia and returned toward normal with normalization of serum calcium in all the patients, and showed significant correlation with serum calcium (QoTc: r = -0.77, p less than 0.001, n = 35; QaTc: r = 0.82, p less than 0.001, n = 35). QaTc was short (less than 0.30 s) in all the ECGs in severe and moderate hypercalcemia and in 2 of the 5 ECGs in mild hypercalcemia. Combination of short QoTc (less than 0.18 s) and short QaTc was found to be highly specific for, and was present in 65% of ECGs, in moderate and severe hypercalcemia. Combination of normal QoTc (greater than 0.18 s) and normal QaTc (greater than 0.30 s) was not observed in moderate or severe hypercalcemia. We conclude that QoTc and QaTc intervals are reliable indicators of clinical hypercalcemia. PMID- 2899467 TI - Fatal bone marrow toxicity in a patient treated with methotrexate and glafenine for rheumatoid arthritis. PMID- 2899468 TI - Takayasu's arteritis and bilateral sacroiliitis. PMID- 2899469 TI - The predictive value of computed tomography and Haemophilus influenzae capsular antigen in subdural fluid collections. AB - A study was made of 52 patients with Haemophilus influenzae type B meningitis complicated by subdural collections of fluid to determine which of these collections were sterile (effusions) and which infected (empyema). This differentiation is important for the treatment which differs in the two conditions. Cranial computed tomography (CT) alone was not as reliable as the combination of CT associated with detection of Haemophilus influenzae capsular antigen, in accurately predicting if a subdural fluid collection was infected, or had a high probability of becoming infected. PMID- 2899470 TI - Effects of nonionizing radiation on birds. AB - 1. With the ability to fly comes a greater probability of direct irradiation by nonionizing radiation. The effect of nonionizing radiation on birds is, therefore, of environmental significance. 2. Most biological effects of exposure to nonionizing radiation in avian species are a result of radiation-induced temperature increases. 3. The incubating avian egg provides a model to study nonthermal effects of microwave exposure since ambient incubation temperature can be adjusted to compensate for absorbed thermal energy. 4. Some studies have shown that exposure to nonthermal levels of nonionizing radiation affect a bird's ability to recover from acute physiological stressors. 5. Although earlier research indicated that modulated radiofrequency radiation increased calcium-ion efflux in chick forebrain tissue, criticism of experimental techniques and contradictory results between related studies have made final conclusions elusive. 6. Birds have been shown to be able to reliably detect magnetic fields in both the field and laboratory. Some researchers have reported malformations in chicken embryos exposed to a sinusoidal bipolar oscillating magnetic field. PMID- 2899471 TI - Serum enzymes in hemorrhaged Japanese quail after microwave irradiation during embryogeny. AB - 1. Japanese quail eggs were exposed to 2.45 GHz continuous wave microwave radiation at an incident power density of 5 mW/cm2 and a specific absorption rate of 4.03 mW/g during the first 12 days of embryogeny. 2. After hatching, serum biochemical changes in response to hemorrhagic stress were measured following a hemorrhage of 30% of the calculated total blood volume. 3. Lactate dehydrogenase, beta-glucuronidase, acid phosphatase, glucose and protein were not affected by microwave irradiation during embryogeny either before or after hemorrhage. 4. Microwave irradiation in ovo affected the response of serum glutamic oxaloacetic transaminase activity to hemorrhagic stress in Japanese quail. PMID- 2899472 TI - Kidney function in response to salt feeding in rainbow trout (Salmo gairdneri Richardson). AB - 1. The effect of high levels of dietary salt up to 12% NaCl on kidney function in freshwater rainbow trout was investigated. 2. Renal response to dietary NaCl load includes increases in urinary flow rate and glomerular filtration rate, together with a slight reduction in ionic reabsorption capacity. 3. The renal salt excretion rate, which was doubled to about 100 microM/kg/hr, in fish fed the high salt diet, is not entirely a consequence of a reduction in tubular ionic reabsorption but also of increased glomerular filtration. 4. The role of the endocrine system in control of renal salt excretion is discussed. PMID- 2899473 TI - The effect of alkaline earth cations and of ionic strength on the dissociation of earthworm hemoglobin at alkaline pH. AB - 1. The effect of alkaline earth cations on the dissociation of the extracellular hemoglobin of Lumbricus terrestris and the effect of ionic strength on the dissociation of the hemoglobins of L. terrestris and Tubifex tubifex at concentrations of ca 2.5 mg/ml, over the pH range 9.0-10.5 was investigated using ultracentrifugation to separate the dissociated from the undissociated molecules. 2. Mg(II), Ca(II) and Sr(II) at concentrations of up to 0.2 M, decreased the dissociation of Lumbricus oxyhemoglobin from 70% at pH 9.0 and 100% at pH 9.5 and higher, to 20-30% at 0.05 M. The three cations were equally effective in decreasing the extent of dissociation of L. terrestris oxyhemoglobin over the pH range 9.0-10.5, with a K1/2 of ca 10 mM. 3. The dissociation of L. terrestris oxyhemoglobin over the pH range 9.0-10.5 was decreased only to 50-60% in the presence of up to 0.5 M NaCl or KCl; there was no further decrease in dissociation at concentrations of the two salts up to 1.5 M. 4. The dissociation of T. tubifex oxyhemoglobin over the pH range 9.0-10.0 was decreased from 100% to ca 40-50% in the presence of 0.5 M NaCl or KCl with little or no change at higher concentrations. At pH 10.5 and 11.0 the decrease in dissociation was more gradual, reaching ca 50% at 1.5 M NaCl. PMID- 2899475 TI - Oxygen transport properties of blood in two different bovine breeds. AB - 1. The whole oxygen dissociation curve of oxyhemoglobin has been determined in double-muscled cattle of the Belgian White Blue breed and in Friesian cattle of different body weight. 2. In calves, P50 values are low and DPG level is high (4 20 mumol/g Hb). 3. P50 values of 25 +/- 1.4 mm Hg (mean +/- SD) and a level of DPG less than 1.5 mumol/g Hb have been found in animals weighing more than 80 kg. 4. Effects of temperature and pH on the oxygen dissociation curve have been measured at all levels of saturation. The temperature coefficient (dlog P50/dT) and the Bohr effect expressed as dlog P50/dpH were 0.017 and -0.40, respectively. 5. Hematocrit, hemoglobin concentrations and oxygen capacity of hemoglobin have been measured. 6. No difference between both breeds has been observed. 7. These data can be used to correct measured values of oxygen tension for temperature and pH and to measure oxygen content of blood in cattle. PMID- 2899474 TI - Comparative quantitation of the physiological response to acute stress in impala and roan antelope. AB - 1. The concentrations of 8 variables in the blood of impala and roan antelope exposed to acute stress were investigated. 2. An objective measure of the acute stress response, based on the % maximal change of the 8 variables, is suggested. 3. The method takes into account the species specificity of the stress response and is based on changes in the concentration of variables which reflect the (general) hormonal and (neuro-) endocrine balance of an animal at a given time. 4. The species-specific experimental response to stress (SSERTS), thus obtained, is time and procedure dependent. PMID- 2899476 TI - Iron-binding properties and amino acid composition of marsupial transferrins: comparison with eutherian mammals and other vertebrates. AB - 1. Some physicochemical properties of transferrin from three marsupials, viz a possum (Trachosurus vulpecula), a kangaroo (Macropus fuliginosus) and the quokka (Setonix brachyurus) were studied and compared with those of transferrins from mammalian and non-mammalian vertebrate species. 2. The molecular weight of the marsupial transferrins fell within the range of 76,000-79,000 daltons. 3. The marsupial transferrins were similar to the transferrins of eutherian mammals with respect to optical spectral properties, iron binding capacity and the pH dependence of iron binding, and iron release mediated by 2,3-DPG. 4. The amino acid compositions of the marsupial transferrins were compared with each other and with the transferrins from the other vertebrate species. The compositions of the marsupial transferrin were closely related to each other, and also showed similarities with transferrins from eutherian mammals and chicken ovotransferrin. PMID- 2899477 TI - Metabolism and evaporative heat loss in the dik-dik antelope (Rhynchotragus kirki). AB - 1. Under controlled conditions, the rate of oxygen consumption (VO2) respiratory frequency, evaporative water loss, heat balance, rectal (Trec) and surface temperatures were determined in the dik-dik antelopes at ambient temperatures (Ta) ranging from 1 to 44 degrees C. 2. The thermal neutral zone was found to be between 24 and 35 degrees C. 3. Respiratory frequency ranged between 27 and 630 breaths/min. 4. At a Ta of 44 degrees C, 95% of the heat produced by the dik-dik was lost via respiratory evaporation. Despite an increase in Trec, cutaneous evaporation did not increase. 5. During panting, VO2 increased in accordance with the expected Q10 effect, contrary to earlier findings. 6. Measurements of circadian rhythm [LD 12:12 (7-19) CT26 degrees C] in VO2 showed that the minimum VO2 (0.42 ml O2/g/hr) occurred at midnight while the maximum (0.78 ml O2/g/hr) occurred at midday. The 24 hr mean VO2 was 0.61 ml O2/g/hr. 7. These measurements suggest that in nature, determinants other than light may be responsible for triggering the variations observed in VO2. PMID- 2899478 TI - Non-gonadal mediated effect of photoperiod on hibernation and body weight cycles of the European hamster. AB - 1. Sexually active male European hamsters raised under short photoperiod display high levels of plasma testosterone, high body weight and do not hibernate. 2. Castrated males in May, raised under the same conditions, do not hibernate and do not present the physiological body weight rhythm. 3. Normal and castrated animals under natural conditions enter hibernation and display a normal body weight rhythm. 4. Normal and castrated animals not submitted to the natural succession of long and short days do not enter hibernation. 5. Photoperiod directly controls body weight and hibernation gonadal interactions. PMID- 2899479 TI - The pneumostome rhythm in slugs: a response to dehydration controlled by hemolymph osmolality and peptide hormones. AB - 1. One response of the terrestrial slug, Limax maximus to dehydration is the initiation and modulation of the pneumostome rhythm. When a slug has lost 15-20% of its initial body weight by evaporation, the frequency of pheumostome closures, which is less than 0.5 closures/min in fully hydrated slugs, begins to increase. 2. The frequency increases with further dehydration, but the average duration of each closure remains constant. Thus, the proportion of time during which the pneumostome is closed increases. Simultaneously, the area of the pneumostome opening decreases. 3. This behavior appears to be controlled in part by both the osmolality of the slug's hemolymph and by a peptide closely related to arginine vasotocin (AVT) and arginine vasopressin (AVP). Injecting intact slugs with mannitol, which increases the osmolality of the hemolymph, or with AVT or AVP, can initiate the pneumostome rhythm. 4. Mannitol injections, however, do not provoke the decrease in the area of the pneumostome opening which is induced by natural dehydration or by AVT or AVP injection. This suggests that at least two systems may be involved in the overall control of the pneumostome. PMID- 2899480 TI - A simple and inexpensive tonometry system for use with microlitre blood samples. AB - The construction of a blood tonometering system based on the vibrating action of a firebell is described. Its performance has been assessed with human blood at 37 degrees C and in use with Antarctic fish blood (Pagothenia borchgrevinki) at -1.5 degrees C. PMID- 2899481 TI - Electrical currents associated with rhythmic contractions of the blastoderm of the medaka, Oryzias latipes. AB - 1. We used a vibrating probe to measure extracellular electrical currents near the surface of dechorionated Oryzias latipes eggs as contraction waves moved slowly across the blastoderm. 2. Although we found no detectable current outside dechorionated embryos, we recorded large current pulses near the edge of wounds made in the surface of the blastoderm. 3. The maximum net inward current--or in some cases, the least net outward current--correlated temporally with the contraction of cells near the edge of the wound. 4. The current pulses were superimposed on steady currents of variable magnitude and polarity. 5. We discuss possible mechanisms for the initiation and propagation of the contraction wave. PMID- 2899482 TI - An investigation of an estrogen-binding component in the liver and plasma of brook char, Salvelinus fontinalis. AB - 1. Estrogen-binding activity was investigated in liver nuclear and cytosolic preparations of sexually mature female brook char, Salvelinus fontinalis. Nuclear salt extracts of estrogen-injected fish were found to contain high affinity binding sites (Kd = 1.6 nM, capacity = 2.8 fM/ug DNA). 2. Low levels of high affinity specific binding activity were found in the cytosol of both injected and untreated fish (Kd = 7.5 nM, capacity = 16.1 fM/mg protein). 3. Binding sites in both preparations were specific for estrogens with no significant competition by 5 alpha-dihydrotestosterone, progesterone, or cortisone. 4. A plasma-binder was found to have distinctive differences with regard to structural specificity compared to the estrogen-binding component in liver. It was found to have no affinity for diethylstilbestrol while having some affinity for both 5 alpha dihydrotestosterone and progesterone. 5. The brook char liver estrogen-binding component was observed to have characteristics in common with estrogen receptors found in other vertebrates. PMID- 2899483 TI - Olfactory deprivation in pigeons: examination of methods applied in homing experiments. AB - 1. Effectiveness of three methods of olfactory deprivation or impairment was tested by means of unconditioned cardiac acceleration in response to odorous stimuli. 2. Occlusion of nostrils reduced stimulus intensity to approx. 20-30% of the level in unimpeded state. Capability of stimulus quantification remained unimpaired. 3. Bilateral olfactory nerve section and backward bending of the nerve stumps irreversibly eliminated responses to weaker stimuli. With higher concentrations of the odorant, pigeons responded at a reduced level, most likely due to trigeminal reception. 4. Spraying the nasal cavities with an anaesthetic largely abolished sensitivity to odorous stimuli. However, its effect was quite variable depending on the kind of application (which cannot be fully standardized). The time course of effectiveness is shown. 5. The relevance of these findings to experiments on pigeon homing is discussed. Conclusions on involvement of unspecified non-olfactory stimuli can only be drawn if methods are applied that reliably isolate the birds from airborne environmental odours. PMID- 2899484 TI - Intra-arterially administered vasopressin inhibits nocturnal pineal melatonin synthesis in the rat. AB - 1. In order to investigate the possible involvement of arginine-vasopressin (AVP) in the inhibition of nocturnal pineal melatonin synthesis following electrical stimulation of the hypothalamic paraventricular nuclei, adult male rats received injections of 5 micrograms/100 g body weight of the peptide during either day- or night-time. Following survival times of 30 or 120 min, animals were killed and the activity of the melatonin synthesis enzyme N-acetyltransferase (NAT) was determined. 2. At night, NAT activity was significantly decreased 30 and 120 min following AVP injection. 3. During the daytime, NAT activity was unchanged following AVP administration. 4. It is suggested that pineal melatonin synthesis may be affected by PVN stimulation not only via neural pathways but possibly also by PVN-released blood-borne AVP. PMID- 2899486 TI - The relationship between food intake, body fat and reproductive inhibition in prairie deermice (Peromyscus maniculatus bardii). AB - 1. Reproductively-inhibited deermice selected from four laboratory populations consumed significantly less food than reproductively-proven pairs. 2. Reproductively-inhibited animals predominantly, but not consistently, had reduced total body fat compared with reproductively capable deermice. 3. The per capita food consumption rate of two populations followed for 26 weeks since founding, decreased over time to about 65% of the daily intake of the proven animals used to found the populations. 4. An aggregation or "huddling" behaviour with concomitant reduction in thyroid hormone activity, possibly in response to the density of the "huddle", is suggested as an explanation for these observations. PMID- 2899485 TI - Effects of cholecystokinin peptides on digestive enzymes in killifish in vivo. AB - 1. The abilities of cholecystokinin-like peptides to elicit lipase secretion were examined in the stomachless killifish, Fundulus heteroclitus. 2. Cholecystokinin octapeptide, caerulein, and nonsulfated caerulein stimulated lipase secretion in vivo, with caerulein and nonsulfated caerulein being the most potent peptides tested. 3. Lipase secretion was not induced by carbachol, and peptide stimulated lipase secretion was not inhibited by atropine. 4. These data suggest digestive enzyme secretion constitutes an evolutionary primitive role for CCK. PMID- 2899487 TI - Characteristics of the water response across the dorsal epithelium of frog tongue. AB - 1. Dorsal epithelium of the frog tongue produced a change in potential difference across the tissue in response to removal of NaCl from the adapting Ringer solution on the mucosa. 2. The response was not caused by an osmotic decrease in the stimulus, and its profile was in many respects similar to that of the receptor potential in frog taste cells. 3. In conclusion, the response may influence or modify water reception in frogs. PMID- 2899488 TI - Lactate utilization and influx in resting and working rat red muscle. AB - 1. The behavior of lactate was studied during electrical stimulation and influx was measured under resting conditions of rat soleus muscle. 2. Lactate utilization was measured with (U-14C) lactate and results from electrical stimulation of the soleus muscle present evidence that this substance is mainly oxidized. 3. Under resting conditions, lactate influx showed a saturable transport system with an apparent Km of 11 mM. This low affinity for lactate suggests that lactate transport has a limiting factor for the muscle. 4. The increased lactate utilization under electrical stimulation (1,114 +/- 344 mumol/g/hr, at 20 mM lactate) corresponds to increased lactate permeability as compared to the influx rate (20.81 +/- 1.65 mumol/g/hr at 20 mM lactate) in resting conditions. 5. Alanine, epinephrine or S.I.T.S. 4-amino 4'isothiocyanostilbene-2-2'-disulphonate) do not affect lactate permeability in the soleus muscle. PMID- 2899489 TI - Thermoregulation in the largest African cricetid, the giant rat Cricetomys gambianus. AB - 1. Thermoregulation, metabolism and minimum conductance in Africa's largest cricetid, Cricetomys gambianus (1870.9 +/- 194.2 g), were investigated. 2. A mean minimal resting metabolic rate of 0.61 +/- 0.09 ml O2/g/hr (139% of that predicted), a minimal conductance of 0.04 +/- 0.01 ml O2/g/degrees C/hr (195% of that predicted), a thermoneutral zone from 21 to 34 degrees C and a mean body temperature of 35.6 +/- 1.1 degree C below an ambient temperature of 20 degrees C were found. 3. It was concluded that giant rats are physiologically adapted to burrowing habits, but only within cool environments, and are precluded from exploiting drier areas. PMID- 2899490 TI - Prazosin, an adrenergic blocking agent inadequate as male contraceptive pill. AB - The purpose of this study was to investigate the efficacy and the acceptability of Prazosin as a male contraceptive pill. Acceptable antifertility drugs for men are proving difficult to produce, and the possibility of using pharmacological agents to block selectively or to inhibit normal sperm transport through the male genital tract is an interesting approach. Prazosin administered in doses up to 10 mg/day did not cause azoospermia following ejaculation. In conclusion, we have not been able to confirm either the efficacy or the acceptability of the alpha 1 adrenoceptor antagonist Prazosin as a male contraceptive drug. Homonnai et al. confirmed the fact that phenoxybenzamine blocks ejaculation, but it should be noted that although both drugs are alpha 1-adrenoceptor blocking agents, they are not chemically identical. PMID- 2899491 TI - Use of histamine2-receptor blocking agents and sucralfate in a health maintenance organization following continued clinical pharmacist intervention. AB - The effect of continued clinical pharmacist intervention on the proper use of histamine2-receptor blocking agents and sucralfate in a health maintenance organization was studied. New prescriptions written for cimetidine, famotidine, ranitidine, and sucralfate in January 1986 (preintervention), October 1986 (postintervention), and February 1987 (follow-up), and the medical record of each patient were analyzed for appropriateness using approved criteria. Clinical pharmacist intervention occurred throughout the study. There was a significant decrease (p less than 0.005) in the rate of inappropriate prescribing in the postintervention (42.4 percent) and follow-up (48.7 percent) periods versus the preintervention period (81.5 percent), and in the average number of refills authorized per patient in the postintervention (1.2 +/- 1.54) and follow-up (1.3 +/- 1.00) periods versus the preintervention period (3.0 +/- 3.67). There were no significant differences in these areas between the postintervention and follow-up periods (p greater than 0.05). A benefit-to-cost ratio of 4.3:1 was generated from this study which demonstrated that continued clinical pharmacy interventions can have a positive, cost-effective impact on the proper use of these commonly prescribed medications. PMID- 2899492 TI - Neuroleptic rechallenge after neuroleptic malignant syndrome: case report and literature review. AB - Neuroleptic malignant syndrome (NMS) is associated with essentially all of the currently available antipsychotic agents. The signs and symptoms associated with the syndrome are hyperpyrexia, defined by body temperature greater than 38 degrees C; extreme muscle rigidity, with or without elevated creatine phosphokinase or hyperreflexia; and other symptoms such as altered level of consciousness and/or autonomic dysfunction as manifested by labile blood pressure, tachycardia, tachypnea, urinary or fecal incontinence, pallor, or diaphoresis. This potentially fatal syndrome complicates the treatment of patients with recurrent psychotic symptoms because of the possibility for recurrence of the NMS. A case of recurrent NMS is presented in which the patient was rechallenged with an antipsychotic agent. In addition, 41 reported cases of antipsychotic rechallenge after NMS are reviewed. The results of the review suggest that neuroleptic rechallenge following NMS is associated with an acceptable risk of recurrence in most patients. However, close monitoring for NMS and careful selection of patients for antipsychotic rechallenge is mandatory. A minimal time period of five days before rechallenge may also reduce the risk of recurrent NMS. Recurrence was not associated with patient age or gender, nor the antipsychotic agent used. PMID- 2899493 TI - Generalized convulsions in a patient receiving ultrashort-acting beta-blocker infusion. AB - Beta-receptor blocking agents are commonly used to treat patients with heart disease, and generalized seizures due to therapy with these agents are rare. All reported cases of seizures due to beta blocking agents have occurred only in those subjects who ingested large doses of the drugs. We observed generalized convulsions in a patient who was receiving therapeutic doses of an ultrashort acting beta-blocking agent (esmolol hydrochloride) intravenously. A literature survey and possible mechanisms by which these agents induce seizures are presented. PMID- 2899494 TI - Antihypertensive treatment according to age, plasma renin and race. AB - Recent large scale antihypertensive treatment trials emphasise the importance of blood pressure control in reducing both cerebrovascular accidents and myocardial infarction. Obviously therefore, the drug that best normalises blood pressure while producing the fewest adverse effects should be sought. On the basis of studies demonstrating cellular membrane and calcium homeostatic derangements and an age-dependent transition of overall cardiovascular regulation and peripheral vasoconstrictor forces during the course of essential hypertension, this review proposes an alternative treatment. Under this treatment scheme angiotensin converting enzyme inhibitors or beta-blockers should be used in younger patients and in those with high plasma renin activity, while calcium antagonists are used in place of diuretics in older low-renin or Black patients. Age-oriented 2-way drug selection enables a normalisation of blood pressure without untoward effects in about 80% of patients with essential hypertension and helps to optimise drug combinations in those patients who are difficult to treat. PMID- 2899496 TI - Cefotaxime lavage in children undergoing appendicectomy. AB - In an attempt to reduce postoperative sepsis, a series of randomised, double blind studies was begun in 1982, using cefotaxime as backbone therapy. Up to 1985 (stages I and II), the best results were obtained using a combination of cefotaxime (75 mg/kg intravenously in 3 doses at 12-hourly intervals) plus metronidazole (10 mg/kg intravenously in 3 doses), both drugs administered 1 hour before surgery (preoperatively) or at anaesthetic induction (peroperatively). In 300 consecutive cases, the wound infection rates were 1% in uncomplicated acute appendicitis and 5% in perforated/gangrenous appendices. The present study (stage III) reports the findings in 401 consecutive patients: 215 treated with the above regimen, either pre- or perioperatively (group 1) and 186 who additionally had peritoneal lavage with cefotaxime 2 g/L during surgery (group 2). There were 16 wound infections overall, 2 among patients administered prophylaxis preoperatively and 14 in those administered prophylaxis perioperatively. All produced mixed cultures, with Escherichia coli, Streptococcus milleri and Bacteroides fragilis predominating. The overall figures for postoperative sepsis are 12/215 (5.6%) in the non-lavage group and 8/186 (4.3%) in the lavage group. Among patients with a perforated and/or gangrenous appendix, the wound infection rate was 8/72 (11.1%) in the non-lavage group (group 1) and 4/66 (6.1%) in the lavage group (group 2). Each group had 2 cases of pelvic abscess. PMID- 2899497 TI - Immunoreactive growth hormone-releasing hormone in rat placenta. AB - It has been shown that immunoreactive and biologically active GH-releasing hormone (GHRH)-like material is present in rat placenta. To investigate the role of placental GHRH, we measured it in human and rat placenta of different gestational stages, using specific RIA systems. GHRH and somatostatin contents in median eminence, pituitary GH contents, and plasma GHRH levels were also quantified in rats. Immunoreactive GHRH was detectable in rat placenta [13 days of gestation, 1.4 +/- 0.4 (+/- SD); 16 days, 1.4 +/- 0.2; 20 days, 1.7 +/- 0.4 ng/g] but not in human placenta (less than 0.06 ng/g in both full-term and mid term placenta). GHRH concentrations in rat placenta did not change significantly during pregnancy, but total contents increased progressively in relation to placental growth. GHRH and somatostatin contents in median eminence of pregnant rats were not different from those of control female rats. In contrast, rat pituitary GH contents in pregnant rats were significantly lower than those of control female rats. Immunoreactive GHRH was not detectable in plasma of either pregnant rats or nonpregnant rats. Molecular sieve chromatography revealed two peaks of immunoreactive GHRH in rat placental extracts: a major peak eluted in the position of synthetic rat GHRH and a minor peak in the higher molecular weight region. In contrast, a single peak in the position of rat GHRH was observed in rat median eminence extracts. Detection of immunoreactive GHRH in rat placenta but not in human may suggest that the mechanism of GHRH gene expression in placenta is species specific. Failure of detection of immunoreactive GHRH in rat maternal circulation suggests that placental GHRH may not affect the maternal hypothalamic pituitary axis. Presence of high molecular weight materials of immunoreactive GHRH in rat placenta but not in median eminence suggests that posttranslational processing of the GHRH precursor molecule may be different in the two organs. Placental GHRH may have a paracrine function or may be secreted into fetal circulation and contribute to fetal growth. PMID- 2899495 TI - Doxazosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in mild or moderate hypertension. AB - Doxazosin is a long-acting selective alpha 1-adrenoceptor antagonist structurally related to prazosin. Like prazosin, doxazosin exerts its antihypertensive effect by reducing total peripheral resistance by selective postsynaptic alpha 1 blockade, without reducing cardiac output, and similarly, doxazosin appears to have a negligible effect on heart rate. Doxazosin differs from prazosin in that its long half-life enables once-a-day oral administration. Doxazosin significantly lowers both standing and supine blood pressure and appears to maintain this antihypertensive effect over a 24-hour dosing interval. Doxazosin 1 to 16 mg once daily has been found to be comparable in efficacy to atenolol 50 to 100 mg and prazosin 1 to 20 mg daily. Characteristic of alpha 1-adrenoceptor antagonists, doxazosin also has favourable effects on the plasma lipid profile in that it decreases total cholesterol and triglycerides, and increases high density lipoprotein (HDL) cholesterol as well as the HDL/total cholesterol ratio. Although further long term trials are needed to clarify the role of doxazosin in multidrug regimens in more severe hypertension, it appears to be a suitable drug for consideration as first-line therapy in mild to moderate essential hypertension. PMID- 2899498 TI - Inhibitory effect of hypothalamic medial preoptic area somatostatin on growth hormone-releasing factor in the rat. AB - Possible inhibitory effects of somatostatin (SRIF) on GRF were studied by assessing spontaneous GH secretion and GRF content and release in adult male rats depleted of hypothalamic SRIF by anterolateral hypothalamic deafferentation (AHD) or electrolytic lesions in the medial preoptic area (MPO). Plasma GH levels were measured 7 days postoperatively every 20 min in conscious animals with indwelling iv cannulae. Median eminence SRIF was markedly reduced 8 days postoperatively in both AHD and MPO rats, as determined by immunohistochemistry and RIA (P less than 0.01). Although GRF immunoreactivity in the median eminence of AHD and MPO animals appeared well preserved immunocytochemically, hypothalamic GRF content by RIA was significantly decreased at 8 days (P less than 0.01). Spontaneous GH secretion was pulsatile in sham-operated animals. In contrast, basal GH levels in AHD and MPO animals were markedly elevated (P less than 0.01), and secretory pulses were absent. Intravenous injection of specific anti-GRF serum into MPO animals decreased the elevated plasma GH levels (P less than 0.01), indicating increased hypothalamic GRF secretion. GRF release from hypothalamic median eminence-arcuate nucleus complexes in vitro was significantly greater in AHD and MPO animals than in control animals 4 and 8 days postoperatively in response to 30 mM K+ (P less than 0.01), but not under basal conditions. These results suggest that hypothalamic medial preoptic area somatostatinergic neurons play a tonic inhibitory role in the regulation of GRF release and that GH hypersecretion observed after MPO and AHD is attributable to changes in both SRIF and GRF. PMID- 2899499 TI - Distribution of progestin-concentrating cells in rat brain: colocalization of [3H]ORG.2058, a synthetic progestin, and antibodies to tyrosine hydroxylase in hypothalamus by combined autoradiography and immunocytochemistry. AB - The anatomical distribution of progestin-concentrating cells in rat brain was investigated by thaw-mount autoradiography. Fifteen 23-day-old ovariectomized and adrenalectomized female Holtzman rats were injected sc with 5 micrograms 17 beta estradiol in oil/100 g BW daily for 4 days. On the fifth day, all animals were injected iv with 1 microgram/100 g BW [3H]ORG.2058, a synthetic progestin. The animals were killed after 30 or 60 min, and the brains were frozen and processed for autoradiography. Nuclear concentration of radioactivity was found in certain cells of the forebrain and midbrain and was prevented by prior injection (15 min) of excess unlabeled ORG.2058. In the preoptic-septal region, progestin-labeled neurons were observed in the nucleus (n.) septi lateralis, n. interstitialis striae terminalis, n. preopticus medialis, n. preopticus lateralis, n. preopticus periventricularis, and n. preopticus suprachiasmaticus. In the hypothalamus, labeled neurons were seen in n. periventricularis hypothalami, n. arcuatus hypothalami, n. ventromedialis hypothalami, n. dorsomedialis hypothalami, n. premammillaris ventralis, n. premammillaris dorsalis, and lateral hypothalamus. In the extrahypothalamic region, a few labeled cells were found in the central, medial, and cortical nuclei of the amygdala, the organum subforniculare, the lateral geniculate nucleus, the parietal and entorhinal cortex, and the central gray of the midbrain. Some of the progestin-concentrating cells were characterized with combined autoradiography and immunocytochemistry. Tyrosine hydroxylase-containing cells of the arcuate nucleus and the hypothalamic periventricular nucleus (group A12) showed nuclear concentration of radioactivity. Tyrosine hydroxylase cells in groups A11, A13, and A14; the substantia nigra (group A9); and the ventral tegmental area (group A10) did not show nuclear concentration of [3H]ORG.2058. The autoradiographic study demonstrates specific progestin-binding sites in nuclei of neurons in select areas of the rat brain. The results of combined autoradiography and immunocytochemistry suggest, for the first time, a direct action of progestin on tuberoinfundibular dopaminergic neurons. PMID- 2899500 TI - Photoperiodic adjustments in hypothalamic amines, gonadotropin-releasing hormone, and beta-endorphin in the white-footed mouse. AB - This study was undertaken to examine short photoperiod (SD; 8 h of light, 16 h of darkness)-induced alterations in reproductive endocrine and neuroendocrine parameters in the male white-footed mouse, Peromyscus leucopus. Exposure to SD for 8 weeks caused dramatic reductions in testis and seminal vesicle weights, decreased circulating LH and testosterone levels, and lowered the content of LH in the pituitary gland relative to those in mice under long photoperiod (LD; 16 h of light, 8 h of darkness). These changes were associated with significant increases in content of radioimmunoassayable GnRH in the mediobasal hypothalamus (MBH) and anterior hypothalamus at two time points in the light/dark cycle: 2100 h (dark phase) and 0900 h (light phase), respectively. Exposure to SD also caused an increase in radioimmunoassayable beta-endorphin in the MBH and preoptic area of the hypothalamus (POA) at 2100 h, but not at 0900 h. Mice exposed to SD also had a significantly higher metabolism of serotonin in the MBH at 0900 and 2100 h compared to mice under LD. The concentration of noradrenaline in the hypothalamus was unaffected by exposure to SD. However, the metabolism of dopamine (DA) in the POA at 0900 h was significantly increased relative to that in mice maintained under LD at this time. This increase in DA metabolism was associated with enhanced immunocytochemical staining for tyrosine hydroxylase in nerve fibers of the POA. Conversely, staining for tyrosine hydroxylase in tuberoinfundibular DA cell bodies of the arcuate nucleus was less intense under SD exposure. From these data it is concluded that exposure to SD caused regional and time-dependent alterations in the activities of hypothalamic amines (serotonin and DA) and neuropeptides (beta-endorphin and GnRH). These changes may be part of the neuroendocrine mechanism for SD-induced seasonal adaptations. PMID- 2899501 TI - Decrease in number of somatostatin receptors in rat brain after adrenalectomy: normalization after glucocorticoid replacement. AB - The effects of adrenalectomy on somatostatin (SS) concentration and specific binding in cerebral cortex, hippocampus, striatum, and hypothalamus were examined using [125I-Tyr11]SS as the binding ligand. Adrenalectomy did not affect the concentration of SS-like immunoreactivity in the brain areas studied. Nevertheless, the number of SS receptors was significantly decreased in membrane preparations from hippocampus, striatum, and hypothalamus, but not in cerebral cortex. No significant differences in the apparent binding affinity values were seen after adrenalectomy. The adrenalectomy-induced decreases in [125I-Tyr11]SS receptors were completely reversed by glucocorticoid replacement with dexamethasone. These results demonstrate that adrenalectomy modulates SS receptors in discrete brain areas, suggesting the existence of a possible relationship between corticosteroids and SS in the neuronal activity of these structures. The physiological significance of these findings remains to be clarified. PMID- 2899502 TI - Atrial natriuretic peptide in bovine corpus luteum. AB - Atrial natriuretic peptide (ANP) has been demonstrated to exert endocrine functions, including the modulation of steroid synthesis. This prompted investigations to search for ANP receptors in the corpus luteum, a tissue that produces progesterone. The studies revealed a single binding site for [125I] ANP with similar characteristics (Kd, 122 pM; maximum binding, 18 fmol/mg protein) in all four stages of corpus luteum development. These receptors were demonstrated to stimulate cGMP production upon activation with synthetic ANP. Maximal cGMP synthesis was observed at 10(-7) M ANP, 5 min after activation of receptors. An acidic extract of corpus luteum contained immunoreactive ANP (approximately 220 fmol/g tissue), as indicated by gel chromatography, HPLC, and identification by means of a highly specific ANP antibody. The data do not permit definition of a specific endocrine role of ANP in the corpus luteum. PMID- 2899503 TI - Thyroid hormone action on biosynthesis of somatostatin by fetal rat brain cells in culture. AB - Thyroid hormone (TH) action on somatostatin (SRIF) secretion and synthesis by fetal rat brain cells in culture was studied. Cortical and hypothalamic brain cells were maintained as monolayer cultures for 7-10 days. T3, T4, and [3H] phenylalanine [( 3H]Phe) (40 microCi/plate) were added simultaneously for 48 h. Alternately, cultures were pulse labeled with [3H] Phe for only the last 3 h, after being exposed to TH for 45 h. 3H-Labeled SRIF-like material [( 3H]IR-SRIF) was purified by immunoaffinity chromatography and further characterized by gel filtration in Bio-Gel P-10. Total protein synthesis was determined by the incorporation of [3H]Phe into trichloroacetic acid precipitable proteins. Forty eight-hour T3 treatment had a biphasic effect on secretion of IR-SRIF by both cortical and hypothalamic cells. In cortical cells, low doses of T3 (10(-11) M) significantly increased (P less than 0.01) and high T3 doses (10(-7) M) significantly decreased (P less than 0.05) total IR-SRIF (nanograms per plate); control: 2 +/- 0.25; T3 (10(-11) M): 3 +/- 0.3; T3 (10(-7) M): 1.3 +/- 0.1. Similarly, T4 had a significant stimulatory action at 10(-9) M, being inhibitory at 10(-7) M (picograms/plate); control: 290 +/- 20 T4 (10(-9) M): 510 +/- 40; T4 (10(-7) M): 201 +/- 10. When [3H]Phe was added during the 48 h of the experiment, [3H]IR-SRIF synthesis in response to T3 by cortical cells significantly increased after exposure to 10(-11) M (P less than 0.05) and decreased with 10(-7) M (P less than 0.05). When [3H]Phe was added for only the last 3 h or incubation with T3, the action was inhibitory at both 10(-11) M and 10(-7) M. Trichloroacetic acid precipitable material decreased in a dose response manner between T3, 10( 11) M and 10(-7) M. These findings suggest that at this time of brain development, SRIF synthesis by cortical and hypothalamic cells is affected by TH. PMID- 2899504 TI - A case of active acromegaly with reduced height and type 1 renal tubular acidosis. AB - A 41-year-old man with acromegaly was suffering from chronic, progressive backache and aware of reduction in his body height. Endocrine studies revealed increased glucose non-suppressible serum growth hormone (GH) and serum prolactin (PRL). Pituitary microadenoma was detected by a computerized axial tomogram and subsequently resected by trans-sphenoidal adenomectomy. The tumor proved to be a mixed GH- and PRL-secreting adenoma by electron microscopy and immunoperoxidase staining. Concurrent investigation of backache and reduced height disclosed markedly reduced radiodensity of the spinal bones, bilateral nephrocalcinosis, and hypercalciuria, which were ascribed to renal tubular acidosis (RTA) demonstrated by reduced urinary excretion of acids and insufficient reduction of urinary pH following oral administration of ammonium chloride. From the analogy to certain endocrinopathies, it appears likely that enhanced calcium metabolism and resultant hypercalciuria due to excess GH and PRL have led to the development of RTA, which further enhanced calciuria. Such enhanced calcium metabolism and consequent hypercalicuria conceivably led to accelerated demineralization of the spine and resulted in the reduced height of this patient in his early forties. PMID- 2899505 TI - Ectopic growth hormone-releasing hormone (GHRH) syndrome in a case with multiple endocrine neoplasia type I. AB - A 36-yr-old man with multiple endocrine neoplasia (MEN) type I had an ectopic growth hormone-releasing hormone (GHRH) syndrome due to a GHRH-secreting pancreatic tumor. The immunoreactive (IR)-GHRH concentration in his plasma ranged from 161 to 400 pg/ml (299 +/- 61 pg/ml, mean +/- SD; normal, 10.4 +/- 4.1 pg/ml), and a significant correlation was found between his plasma IR-GHRH and GH (r = 0.622, p less than 0.02). After removal of the pancreatic tumor, the high plasma GH concentration returned to nearly the normal range (42.2 +/- 31.3 to 9.6 +/- 3.8 ng/ml). These changes paralleled the normalization of his plasma IR-GHRH (16.1 +/- 3.8 pg/ml) and some of his symptoms related to acromegaly improved. However, plasma GH (7.7 +/- 1.3 ng/ml) and IGF-I (591 +/- 22 ng/ml) concentrations were high at 12 months after surgery, suggesting adenomatous changes in the pituitary somatotrophs. Before surgery, exogenous GHRH induced a marked increase in plasma GH, and somatostatin and its agonist (SMS201-995) completely suppressed GH secretion, but not IR-GHRH release. No pulsatile secretion of either IR-GHRH or GH was observed during sleep. An apparent increase in the plasma GH concentration was observed in response to administration of TRH, glucose, arginine or insulin, while plasma IR-GHRH did not show any fluctuation. However, these responses of plasma GH were reduced or no longer observed one month and one year after surgery. These results indicate that 1) a moderate increase in circulating GHRH due to ectopic secretion from a pancreatic tumor stimulated GH secretion resulting in acromegaly, and evoked GH responses to various provocative tests indistinguishable from those in patients with classical acromegaly, and 2) the ectopic secretion of GHRH may play an etiological role in the pituitary lesion of this patient with MEN type I. PMID- 2899506 TI - Effect of physical training on immunoreactive gamma-glutamyltransferase in human plasma. AB - The effects of 10-week physical training on both the activity and concentration of gamma-glutamyltransferase (gamma-GT) in plasma were investigated on 7 sedentary healthy male students. The training consisted of running over 5 km, 6 times/week. The maximal oxygen uptake (Vo2max) and 12-min field performance increased significantly after training, from 43.5 and 2,683.7 to 48.1 ml.kg-1.min 1 and 2,931.1 m, respectively. After training the resting plasma gamma-GT concentration decreased to half, whereas the gamma-GT activity did not vary substantially. The training did not affect the response to the Vo2max test of either concentration or activity of gamma-GT. These results may suggest that plasma gamma-GT concentration is useful as an index of the extent of physical training. PMID- 2899507 TI - Comparison of evoked electromyography and mechanical activity during vecuronium induced neuromuscular blockade. AB - The relationship of compound electromyography to mechanical myography was investigated in 20 patients given vecuronium in a dose of 0.1 mg kg-1. Mechanical response was affected less quickly and recovered faster than the electrical response. Although there was a good correlation between the two throughout the study, a shift towards mechanical responses was observed in all cases for the onset of blockade and recovery from blockade. Moreover, during recovery the mechanical responses became greater than the control value in all patients. This was also reflected in the statistically significant difference (P less than 0.05) of the regression lines relating tension and electromyography (TI as well as train-of-four ratio) between onset of, and recovery from, neuromuscular block. PMID- 2899508 TI - DNA analysis of ornithine transcarbamylase deficiency. AB - By analysing the restriction fragment length polymorphism (RFLP) detected by an ornithinetranscarbamylase (OTC) gene specific DNA probe, we followed the segregation of the defective gene in two families with OTC deficiency (X-linked disease). We were able to exclude some female family members as carriers. In one case a doubtful result obtained in a biochemical carrier detection test (by examining the renal orotic acid excretion after a protein load) could be clarified by DNA analysis. In every family with OTC deficiency, carrier detection should be biochemical with additional DNA analysis. Previous results of the biochemical carrier test should be controlled by DNA analysis, especially when "normal" results were obtained. PMID- 2899509 TI - Influence of xamoterol, a partial beta 1-selective agonist, on physical performance capacity and cardiocirculatory, metabolic and hormonal parameters. AB - In a double-blind, random, cross-over study, 14 healthy male volunteers received xamoterol 200 mg (Corwin; C) twice daily or placebo (P) for two seven-day medication periods to investigate effects on physical performance, cardiocirculatory parameters, metabolism and hormone levels during exercise. An oral glucose tolerance test (OGTT) was also done. C showed a positive inotropic effect up to an exercise intensity of 100 W, corresponding to a heart rate of about 100 beats.min-1. Chronotropic regulation of the heart remained unchanged, but the increase in systolic blood pressure was more pronounced and the catecholamines behaved as after P. From 150 W onwards, C exhibited beta-blocking properties; heart rate was reduced by up to 8 beats.min-1; systolic blood pressure remained unchanged; and the catecholamines showed a more pronounced increase than after P. Diastolic blood pressure behaved almost identically under all test conditions. With the exception of a slightly increased level of free fatty acids at rest, the parameters of physical performance, lipid and carbohydrate metabolism and the hormone levels under all conditions after C showed similar behaviour to that after as P. The findings indicate that physical performance capacity, cardiocirculatory system, metabolism and hormones were not negatively influenced by C. PMID- 2899510 TI - Beta-blockade antagonism of tyramine-induced rise in blood pressure. AB - The effect beta-adrenoceptor blockade on the pressor response to tyramine has been investigated in 6 healthy volunteers, each submitted to an i.v. tyramine pressor test before and after 7 days of propranolol 40 mg b.d. or indenolol 60 mg o.d. Tyramine was given as i.v. boluses of 1-6 mg, alternating with saline, in a randomized, single blind fashion. Prior to treatment tyramine caused a temporary, dose-dependent increase in systolic and diastolic blood pressure, whilst the heart rate remained unaffected. Both propranolol and indenolol reduced the pressor response to tyramine, as shown by a significant increase in ED15, i.e. the dose of tyramine required to increase systolic blood pressure by 15%. PMID- 2899512 TI - Effects of somatostatin on self-stimulation behaviour in rats pretreated with a receptor blocker. AB - The effects of somatostatin on lateral hypothalamic self-stimulation were investigated in rats pretreated with haloperidol, bicuculline, phenoxybenzamine or propranolol. Somatostatin decreased the rate of self-stimulation. Halperidol, bicuculline and phenoxybenzamine potentiated the somatostatin-induced depression of self-stimulation behaviour. Propranolol had no effect. It is suggested that dopaminergic, GABAergic and noradrenergic systems are involved in the somatostatin-induced depression of self-stimulation. PMID- 2899511 TI - Serum magnesium, calcium, phosphate and PTH following long-term beta-blockade in ischaemic heart disease. AB - In 40 patients with ischaemic heart disease the serum levels of magnesium, parathyroid hormone (PTH), phosphate, calcium, and ionized calcium remained unchanged and within normal limits following treatment for 12 months with alprenolol (n = 20) or placebo (n = 20). No changes occurred during a 2 week withdrawal period. The clinical implication is that the non-cardioselective betablocker alprenolol can be given to patients with ischaemic heart disease without the risk of inducing potentially cardiotoxic disturbances in serum magnesium and serum calcium levels. Whether this applies to cardioselective beta blockers remains to be established. PMID- 2899513 TI - Pharmacologic profile of MDMA (3,4-methylenedioxymethamphetamine) at various brain recognition sites. AB - We report here an in vitro pharmacologic profile for MDMA (3,4 methylenedioxymethamphetamine) at various brain recognition sites. The rank order of affinities of MDMA at various brain receptors and uptake sites are as follows: 5-HT uptake greater than alpha 2-adrenoceptors = 5-HT2 serotonin = M-1 muscarinic = H-1 histamine greater than norepinephrine uptake = M-2 muscarinic = alpha 1 adrenoceptors = beta-adrenoceptors greater than or equal to dopamine uptake = 5 HT1 serotonin much greater than D-2 dopamine greater than D-1 dopamine. MDMA exhibited negligible affinities (greater than 500 microM) at opioid (mu, delta and kappa), central-type benzodiazepine, and corticotropin-releasing factor receptors, and at choline uptake sites and calcium channels. PMID- 2899514 TI - Intracerebral SCH 23390 and catalepsy in the rat. AB - Stereotaxic injection of SCH 23390 (D-1 antagonist), but not water or ritanserin (5-HT antagonist), into all parts of the caudate-putamen, elicited an immediate and often long-lasting catalepsy in 79% of rats. Similar results were obtained with SCH 23390 delivered into the nucleus accumbens and globus pallidus, but not into a variety of other brain sites. The results support the idea that SCH 23390 induced catalepsy is related to the occlusion of dopamine D-1 receptors in the forebrain, particularly the striatum, although the topography of the catalepsy evoked by intrastriatal SCH 23390 did not match the distribution of D-1 sites labelled in autoradiographic studies. PMID- 2899515 TI - Long-term motor stimulant effects of (+)-4-propyl-9-hydroxynaphthoxazine (PHNO), a dopamine D-2 receptor agonist: interactions with a dopamine D-1 receptor antagonist and agonist. AB - Rats were given continuous infusions of (+)-4-propyl-9-hydroxynaphthoxazine (PHNO, 5 micrograms/h), a dopamine D-2 receptor agonist, using subcutaneous implants of ALZET osmotic minipumps. It was observed that tolerance occurred to the motor stimulant effects of PHNO during the light cycle of each day, but not during the dark cycle. Rather, the motor stimulant actions of PHNO were gradually augmented during successive nights. Daytime tolerance to the stimulant actions of PHNO was reversed by a mild environmental stress or by administration of the D-1 receptor agonist, SKF 38393 (6 mg/kg i.p.). Co-administration of the dopamine D-1 receptor antagonist, (SCH 23390, 20 micrograms/h s.c. by ALZET osmotic minipumps), initially blocked the motor stimulant actions of PHNO and also attenuated the reversal of tolerance to PHNO produced by stress, without blocking the actions of stress on activity in vehicle-infused animals. These results indicate that tolerance to the behavioural effects of PHNO may result from a loss of activation of D-1 receptors by endogenous DA. PMID- 2899516 TI - Alpha 2-antagonistic effect of N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride (LON-954). AB - The effect of N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride (LON 954) on alpha 2-adrenoceptors was studied in in vivo and in vitro preparations. Like yohimbine, LON-954 antagonised the clonidine-induced inhibition of twitch responses in the Auerbach's plexus of guinea pig ileum and rat vas deferens preparations. It also reversed the anti-convulsant effect of clonidine on pentylenetetrazol (PTZ)-induced convulsions in the rat, a property shared by yohimbine. However LON-954 failed to prevent the hypothermic response to clonidine in mice. The dissimilarity in action of LON-954 and yohimbine on clonidine-induced hypothermia could be due to the fact that the anticlonidine effect of yohimbine on hypothermia is mediated through its antiserotonin action. The results indicate that LON-954 acts as an alpha 2-antagonist both centrally and peripherally. PMID- 2899517 TI - Entamoeba histolytica: virulence potential and sensitivity to metronidazole and emetine of four isolates possessing nonpathogenic zymodemes. AB - The pathogenic potential of four Entamoeba histolytica isolates obtained from asymptomatic carriers and possessing nonpathogenic zymodemes was compared to four E. histolytica strains obtained from invasive cases of amebiasis and having pathogenic zymodemes. Both xenic and axenic cultures of a number of strains were tested. Determinations of cytopathogenicity were done in vitro by measuring the rates of destruction of tissue cultured monolayers of baby hamster kidney cells by intact amebae or by its cell-free extracts. The in vivo virulence was tested by assessing their capacity to form hepatic abscesses in hamsters or cecal ulcerations in rats. The results obtained show that two of the isolates from asymptomatic carriers (strains SAW 1734R clAR and WI:0385:191) were as virulent as three of the invasive ones (HM-1:IMSS, 200:NIH, and SAW 408). Two other isolates from asymptomatic carriers and one from a dysentery case were avirulent. All the E. histolytica isolates tested were similarly sensitive to metronidazole and emetine (IC50 1-10 micrograms/ml). The results indicate that the pathogenic potential of E. histolytica varies between isolates and can be affected by culture conditions and by the presence or absence of bacterial cells. These findings suggest that virulence does not necessarily correlate with a pathogenic zymodeme. PMID- 2899518 TI - Entamoeba histolytica: potent in vitro antiamoebic effect of gossypol. PMID- 2899519 TI - Effect of high doses of somatostatin on adenylate cyclase activity in peripheral mononuclear leukocytes from normal subjects and from acute leukemia patients. AB - In normal lymphocytes somatostatin non-competitively inhibited basal (ID50 5 x 10(-4) M) and isoproterenol- and forskolin-stimulated adenylate cyclase activity (Ac). In acute leukemia blasts, non-responsive to isoproterenol, forskolin, which activates the catalytic subunit, stimulated and somatostatin inhibited Ac, thus indicating the leukemic enzyme, though defective, retains the inhibitory pathway and catalyst function. PMID- 2899520 TI - Synthesis and dopamine receptors binding affinity of 2-(3-fluoro-4 hydroxyphenyl)ethylamine and its N-alkyl derivatives. AB - The 2-(3-fluoro-4-hydroxyphenyl)ethylamine and its N,N-dialkyl derivatives were synthesized. The affinity of new compounds for dopamine binding sites was measured in a test involving displacement of [3H]SCH 23390 (D-1 selective) and [3H]spiperone (D-2 selective) from homogenized rat striatal tissue. No compound proved effective in displacing [3H]SCH 23390. Two derivatives are selective displacers of [3H]spiperone. PMID- 2899521 TI - [Regional vascular effects of a decrease in adrenergic activity under conditions of a resting state in animals and during immobilization]. AB - Regional changes of circulation after injection of pirroxan, obsidan and ornid depended on functional state of rats. The differences were significant in systemic hemodynamic and regional changes of resistive, transcapillary exchange and the blood volume function of the circulation. PMID- 2899522 TI - [Formation of the regulator factor activating Na,K-ATPase and neuronal uptake of 3H-norepinephrine under the effect of heat shock]. PMID- 2899523 TI - [Clinical studies on abnormal thyroid stimulators in patients with Graves' disease. I. A sensitive assay for thyroid-stimulating antibodies using cultured porcine thyroid cells and polyethylene glycol precipitation of serum]. AB - The activities of thyroid-stimulating antibody (TSAb) in serum from patients with Graves' disease were measured by a sensitive assay, using cultured porcine thyroid cells and the precipitation from serum with polyethylene glycol (PEG), and the activities were compared with those of thyrotropin binding inhibitor immunoglobulin (TBII), measured by the commercial assay kit. Porcine thyroid cells after digestion were cultured for 15-18 hours with TSH of 1-10,000 microU/ml or the precipitations of sera from normal subjects and patients with Graves' disease or Hashimoto's thyroiditis, and then the cAMP levels in the culture medium were determined by the commercial RIA assay kit (Yamasa). The precipitation was obtained by adding 0.5 ml of 30% PEG solution to 0.5 ml serum, and was resuspended with 0.6 ml of Hanks' medium without NaCl, containing 1.5% bovine serum albumin, 20mM Hepes and 0.5 mM 3-isobutyl-1-methylxanthine. The precipitation contained about 85% of immunoglobulin and 63% of albumin of the original amount of the serum, as well as substantial TSH, when the original serum contained TSH more than 40 microU/ml. When the PEG precipitations from 10 normal subjects were incubated with the thyroid cells of 4 X 10(5) cells, the cAMP releases into the medium ranged from 83 to 124%, when the mean value was calculated as 100%. Therefore, the cAMP release of more than 130% of the amount released into the culture medium incubated with normal IgG was judged as positive TSAb activity. The minimum detectable quantities were regarded as about 5 microU/ml TSH equivalent. TSAb and TBII activities were detected in 48 (92%) and 50 (96%) of 52 patients with untreated hyperthyroid Graves' disease, respectively, and either TSAb or TBII activities were detected in 16 (80%) of 20 patients with Graves' disease maintained in a clinically euthyroid state by treatment with antithyroid drugs. TBII was positive in 10(50%) of these patients. Some patients showed distinct discrepancies in these two activities, although there was a significant positive correlation between TSAb and TBII activities (r = 0.53, p less than 0.01) in patients with untreated Graves' disease. In these patients, TSAb activities showed a significant positive correlation with values for 99mTc thyroid uptake, determined 30 min after the injection. However, they did not show any significant correlation with serum T4 or T3 concentrations. Similarly, TBII showed significant correlations with goiter size and 99mTc thyroid uptake. To conclude, the present assay for TSAb is sensitive and reproducible.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2899524 TI - Cholinergic stimulation of phosphoinositide hydrolysis in rat anterior pituitary. AB - The production of inositol phosphates in response to carbachol was studied in rat anterior pituitary tissue prelabelled with [3H]inositol. Carbachol (10 microM) stimulated inositol mono-, bis- and trisphosphate production (IP1, IP2 and IP3) by 360 +/- 49, 338 +/- 49 and 503 +/- 49 (mean +/- SEM, P less than 0.001) percent respectively during a 30 min incubation. Mean basal production was 5.4 +/ 0.3, 4.1 +/- 0.5 and 0.9 +/- 0.3 expressed as a percent of total [3H]inositol lipid for IP, IP2 and IP3 respectively. Stimulated inositol phosphate production was dose dependent and detectable after 5 min. Atropine prevented this stimulation indicating mediation via muscarinic receptors. Removal of extracellular Ca2+ reduced both basal and stimulated total inositol phosphate production by 60% and 56% respectively but did not impair carbachol-induced phosphoinositide hydrolysis per se. Pretreatment of pituitary tissue with either somatostatin (5 micrograms/ml) or pertussis toxin (1 microgram/ml) had no effect on either basal or stimulated inositol phosphate production. These results demonstrate a cholinergic stimulation of phosphatidylinositol bisphosphate (PIP2) hydrolysis in the anterior pituitary which may be important in the action of cholinergic agonists on pituitary hormone secretion. PMID- 2899525 TI - Uterotropic 6-methoxybenzoxazolinone is an adrenergic agonist and a melatonin analog. AB - 6-Methoxybenzoxazolinone (MBOA) is a compound isolated from grasses which has gonadotropic effects in a variety of animals. The weak beta-adrenergic agonist character of MBOA is shown by its in vitro stimulation of adenylate cyclase from several tissues. Tritiated MBOA bound specifically to particulate fractions from uterus is also displaced by alpha- and beta-adrenergic compounds. The adrenergic properties of MBOA suggest it may exert diverse effects including direct actions on gonadotropin synthesis and release. The mixed adrenergic agonist ephedrine and the antidepressant imipramine were also found to be uterotropic in the vole Microtus montanus following injection protocols used with MBOA. MBOA is structurally similar to melatonin (5-methoxy-N-acetyltryptamine); [3H]melatonin which binds to uterine and pineal membranes is displaced by MBOA and by other adrenergic agents. The fact that MBOA is a beta-adrenergic agonist and a melatonin analog can account for stimulatory and inhibitory effects of this compound on sexual development. PMID- 2899526 TI - Calcitonin gene-related peptide and somatostatin inhibit insulin release from individual rat B cells. AB - Hormone secretion from single, rat pancreatic B cells was visualised by a reverse haemolytic plaque assay for C-peptide. Quantitative analysis of the size and number of haemolytic plaques indicated that exposure to 3, 5, 10 and 20 mM glucose resulted in a dose-dependent increase in both the magnitude of C-peptide, and thus, insulin release by individual B cells and the recruitment of activity secreting B cells. Somatostatin and calcitonin gene-related peptide, fragment 28 37 (CGRP28-37) were shown to inhibit glucose-stimulated insulin release as assessed by the size of individual plaques and the number of recruited B cells, and hence to reduce the total area of plaques formed. In the presence of 15 mM glucose, a dose-dependent effect of CGRP28-37 on the secretion of insulin was observed, with the size of plaques formed by individual B cells reduced at concentrations of CGRP28-37 between 10(-5) and 10(-11) M. Thus, both somatostatin and CGRP28-37 can act directly on individual B cells to inhibit their secretory response to increasing levels of glucose. We suggest that these peptides which can be immunolocalised in islet cells may have a role in the regulation of insulin secretion. PMID- 2899527 TI - Malignant pancreatic somatostatinoma in a patient with dermatitis herpetiformis and coeliac disease. AB - A case of malignant somatostatinoma is reported in a patient with long-standing dermatitis herpetiformis and coeliac disease. The patient had non-specific abdominal pain of several years duration and came to attention because of weight loss despite strict adherence to a gluten-free diet. Plasma somatostatin levels were raised, and laparotomy showed a pancreatic tumour with metastases, which on histology, electron microscopy and immunohistochemistry proved to be a somatostatinoma. After a promising initial response to streptozotocin, she died 30 months later. This is the first reported occurrence of a somatostatinoma in a patient with coeliac disease, adding to the growing list of neoplastic complications in this condition. PMID- 2899528 TI - Diet counselling improves the clinical course of patients with Crohn's disease. AB - A prospective study was undertaken to establish the role of individualized diet counselling in the management of 137 outpatients with Crohn's disease. Individualized dietary counselling for 6 months was associated with a significant decrease in the Crohn's disease activity index, an increased incidence of disease remission, a decreased need for prednisone and Salazopyrin therapy, a reduction in the number of days spent in hospital, and a reduction in the amount of time lost from work due to Crohn's disease, when compared with control patients who did not receive dietary counselling but who were seen regularly in follow-up under similar circumstances. Improvement with diet counselling was more likely to occur in patients who had not previously been subjected to small bowel resection, and occurred in patients with active or inactive disease. The effect of counselling 58 patients was assessed over a further 6 months (for a total 12 month period); there was a persistently reduced Crohn's disease activity index and a continued decreased number of lost days of work. The mechanism for these beneficial effects of diet counselling was not established. It is suggested that individualized diet counselling, aimed at optimizing the patient's nutritional status, may play a role in the management of patients with Crohn's disease. PMID- 2899529 TI - Teratology studies of compound LY171883 administered orally to rats and rabbits. AB - The teratogenic potential of the leukotriene antagonist LY171883, a novel antiasthma agent, was investigated in CD rats and Dutch Belted rabbits. Mated female rats were dosed with 0, 10, 65, or 425 mg/kg/day on gestation days 6 through 15 and killed on gestation day 20. Mated female rabbits were dosed with 0, 20, 65, or 200 mg/kg/day on gestation days 6 through 18 and killed on gestation day 28. Maternal toxicity was indicated at 425 mg/kg in rats and 200 mg/kg in rabbits by depressed body weight gain and food consumption. In the rabbit study four abortions occurred at 200 mg/kg, most likely secondarily to maternal toxicity. LY171883 did not cause embryo/fetal toxicity or teratogenicity in rats or rabbits at doses up to and including those that were maternally toxic. PMID- 2899530 TI - Absence of somatostatin receptors in human exocrine pancreatic adenocarcinomas. AB - Somatostatin receptor frequency was evaluated in 12 human exocrine pancreatic carcinomas taken after surgery. The tumors were analyzed by receptor autoradiography on tissue sections and by in vitro binding techniques on tumor homogenates. None of the tested human pancreatic carcinomas was shown to possess specific somatostatin receptors. In comparison, five single tumors taken from rats transplanted with the rat pancreatic adenocarcinoma CA 20948 were found to contain specific high-affinity somatostatin receptors. Also, human endocrine pancreatic tumors, i.e., two insulinomas, did contain somatostatin receptors under identical experimental conditions. These data confirm previous results with other tumors, documenting the absence of somatostatin receptors in highly malignant human carcinomas. They also may represent an explantation at the molecular level for the lack of therapeutic effect of somatostatin analogues such as SMS 201-995 seen in patients with advanced exocrine pancreatic carcinomas. PMID- 2899531 TI - Regulation of gastric somatostatin secretion. PMID- 2899532 TI - Mhc class II DNA polymorphisms within and between chromosomal species of the Spalax ehrenbergi superspecies in Israel. AB - Restriction fragment length polymorphisms (RFLPs) of two major histocompatibility class II genes (P alpha 1 and Q beta) were studied in 13 populations of four chromosomal species (2n = 52, 54, 58 and 60) of the mole rat, Spalax ehrenbergi superspecies in Israel. A substantial frequency of allelic fragments was found in both genes for all populations, including a desert isolate. In the P alpha 1 gene, one allelic fragment is a result of a deletion mutation which is diagnostic of the 2n = 52 chromosomal species. All other ten allelic variants are the result of point mutations. All mutations are located in a short region flanking the 3' end of the gene. Based on Mhc polymorphisms we confirm earlier evidence that gene flow does not occur between the older chromosomal species (2n = 52, 54, 58), and that reproductive isolation decreases, progressively from the oldest to the youngest species (2n = 60). PMID- 2899534 TI - [Use of a method of color writing in assessing the functional status of 6-year old children]. PMID- 2899533 TI - An engrailed class homeo box gene in sea urchins. AB - The homeo box, a conserved DNA element first recognized in Drosophila development controlling genes, is present in the genomes of many higher metazoan species and provides a valuable probe for the isolation of regulatory genes from diverse phylogenetic groups. We have employed these probes to isolate and study the homeo box genes in sea urchins. As in other species, the sea urchin homeo boxes fall into at least two classes defined by nucleotide sequence similarity to the homeo boxes of the Drosophila Antennapedia (Antp) and engrailed (en) genes. In this study, we characterize the only detectable sea urchin en class homeo box. Its nucleotide sequence similarity and lack of an intron indicate that it is more closely related to the two mouse en class homeo boxes than to the two Drosophila en class homeo boxes. These relationships are most parsimoniously explained if the single sea urchin en class homeo-box gene represents the primitive condition and the two mouse and the two Drosophila en class homeo-box genes represent independent duplications which occurred in the evolutionary lines leading to the vertebrates and arthropods, respectively. The most abundant en class gene transcripts detected by gel transfer analysis of RNA extracted from sea urchin tissues were found in Aristotle's lantern. Rare transcripts were present in ovary, testis and coelomocytes. PMID- 2899535 TI - Effects of fasting and refeeding on somatostatin concentration and binding to cytosol from rabbit gastric mucosa. AB - Somatostatin like immunoreactivity and the density of somatostatin binding sites were measured in stomach (fundus and antrum) from either fed, 12 to 96 hours fasted, or 96 hours fasted plus 48 hours refed rabbits. The somatostatin concentration increased in fundic and antral mucosa after 24 h and reached its highest value after 96 h of fasting. The number of specific somatostatin binding sites with high and low affinity decreased with the duration of fasting. Refeeding of fasted animals resulted in a normalisation to control values of gastric mucosal somatostatin and somatostatin binding. PMID- 2899537 TI - Gastric carcinoid tumour and parathyroid adenoma. AB - A case involving a gastric carcinoid in association with parathyroid adenoma is reported and the question of a possible link between these two ailments is discussed. PMID- 2899538 TI - Hormonal regulation of biliary calcium excretion in rats: inhibition of calcitonin action by alpha 1-adrenergic stimulation. AB - The effect of synthetic [Asu1,7] eel calcitonin (CT) and other hormones on biliary calcium excretion was investigated in rats cannulated bile duct. Administration of CT (80 mU/100 g body weight) produced a significant increase in liver calcium and a corresponding elevation of bile calcium content. The increase in bile calcium content was also caused by administration of insulin (0.1 U/100 g), epidermal growth factor (10 micrograms/100 g), glucagon (10 micrograms/100 g), epinephrine (10 micrograms/100 g), norepinephrine (10 micrograms/100 g), 4 beta-phorbol 12-myristate-13-acetate (10 micrograms/100 g) and ATP (1.0 mg/100 g), suggesting that this increase may be a receptors-mediated response. Of these hormones and drugs, norepinephrine, a alpha-receptor mediator, clearly prevented CT effect on biliary calcium excretion. Moreover, phenylephrine, a alpha 1 receptor agonist, caused an inhibition of the CT effect, while the agonist significantly increased biliary calcium excretion. The present study clearly demonstrates that biliary calcium excretion is stimulated by various hormones which increase calcium influx into liver cells, and suggests that the CT action may be inhibited by alpha 1-adrenergic stimulation. PMID- 2899536 TI - Comparison of delayed release 5 aminosalicylic acid (mesalazine) and sulphasalazine in the treatment of mild to moderate ulcerative colitis relapse. AB - Oral formulations of 5-aminosalicylic acid (mesalazine) appear less toxic than sulphasalazine. We have therefore compared sulphasalazine, low dose mesalazine and high dose mesalazine in the treatment of mild to moderate relapse of ulcerative colitis. Sixty one patients (32 men, aged 20-78 years) were randomly allocated to sulphasalazine 2 g daily, mesalazine 800 mg daily, or mesalazine 2.4 g daily in a double blind, double dummy, four week trial. Groups were comparable for age, sex, extent of disease, and pretrial sulphasalazine intake. Four patients were unable to complete the study because of treatment failure (two taking sulphasalazine and two high dose mesalazine). A further two patients taking sulphasalazine developed side effects necessitating withdrawal. Within treatment comparisons revealed significant improvement of: sigmoidoscopic grade in the sulphasalazine group; rectal bleeding, sigmoidoscopic and histological grade in the low dose mesalazine group; stool frequency, rectal bleeding and sigmoidoscopic grade in the high dose mesalazine group. Greater improvement in rectal bleeding (p less than 0.05) and sigmoidoscopic appearances (p less than 0.05) occurred in patients taking high dose mesalazine than in those taking sulphasalazine. In two patients taking high dose mesalazine minor rises of plasma creatinine concentrations occurred, suggesting the need to monitor renal function. PMID- 2899539 TI - The analgesic effect and development of dependency to somatostatin analogue (octreotide) in headache associated with acromegaly. PMID- 2899540 TI - Congenital absence of insulin-secreting cells. AB - A male infant was diagnosed as having diabetes mellitus 1 d after birth and died on the third day. Histological examination of the pancreas showed small and inconspicuous islets of Langerhans that were completely devoid of insulin secreting cells. There was no evidence of insulitis. PMID- 2899541 TI - Conservation and reorganization of loci on the mammalian X chromosome: a molecular framework for the identification of homologous subchromosomal regions in man and mouse. AB - By means of cross-reacting molecular probes, some 18 loci specific for the X chromosome of both man and mouse have been localized on the mouse X chromosome using an interspecific mouse cross involving the inbred SPE/Pas strain derived from Mus spretus. Comparison of the localizations of these loci on the mouse X with their positions on the human X chromosome suggests that intrachromosomal rearrangements involving at least five X chromosome breakage events must have occurred during the period of evolutionary divergence separating primates from rodents. Within the five blocks of chromosomal material so defined, there is for the moment little or no evidence that either chromosomal inversion events or extensive rearrangements have occurred. These data confirm the remarkable evolutionary conservation of the X chromosome apparent in mammalian species, compared to autosomal synteny groups in which both inter- and intrachromosomal rearrangement events appear to have occurred frequently. The breakage events described here for the X chromosome should therefore provide a minimal estimate for the frequency of chromosomal rearrangement events, such as breakage and inversion, which have affected autosomal synteny groups during the evolutionary period separating man from mouse. The definition of the number of chromosome breakage events by which the X chromosomes of these species differ, together with their localization, provides a framework for the use of interspecies mouse crosses for further detailed mapping of particular subchromosomal regions of the human X chromosome and for defining loci in the mouse homologous to those implicated in human congenital diseases. PMID- 2899542 TI - Multiple restriction site polymorphism at the human somatostatin locus: a population study in Italy. AB - Three Italian populations were examined for a multiple restriction fragment length polymorphism tightly linked to the human somatostatin gene. No difference was observed between the three samples. The haplotype frequencies in Italy were found to be: SST ESBS = 0.836, SST ESBF = 0.072, SST EFBS = 0.091 and SST EFBF = 0.001. PMID- 2899543 TI - Studies on the human chromosome 3 centromere with a newly cloned alphoid DNA probe. AB - Starting from a chromosome-specific DNA library, we have isolated a human chromosome-specific satellite DNA sequence. This sequence of 635 base pairs (bp) consists of 3.7 alpha DNA monomers of 170-171 bp. Under high stringency it hybridizes to the centromere of chromosome 3 in a region composed of 2,750 bp tandem repeats characterized by the regular spacing of Hind III and TaqI restriction enzyme recognition sites. It has diverged and undergone amplification after the human speciation. The amplification allows an easy monitoring of the chromosome 3 centromere by in situ hybridization with a nonradioactive probe. PMID- 2899544 TI - Genetic variations of insulin-like growth factor I in Italy. AB - Four Italian populations were examined for a HindIII RFLP associated with the human insulin-like growth factor I gene. No differences were observed among the four samples. The allele frequencies in Italy were: IGF-I HF = 0.834; IGF-I HS = 0.166. The polymorphism appears to be due to a 400-bp sequence insertion-deletion mechanism. PMID- 2899545 TI - Central modulation of peripheral inflammation. PMID- 2899546 TI - Restriction fragment length polymorphism of the major histocompatibility complex of the dog. AB - Human major histocompatibility complex (HLA) cDNA probes were used to analyze the restriction fragment length polymorphism (RFLP) of the DLA-D region in dogs. Genomic DNA from peripheral blood leucocytes of 23 unrelated DLA-D-homozygous dogs representing nine DLA-D types (defined by mixed leucocyte reaction) was digested with restriction enzymes (Bam HI, Eco RI, Hind III, Pvu II, Taq I, Rsa I, Msp I, Pst I, and Bgl II), separated by agarose gel electrophoresis, and transferred onto Biotrace membrane. The Southern blots were successively hybridized with radiolabeled HLA cDNA probes corresponding to DR, DQ, DP, and DO beta genes. The autoradiograms for all nine enzyme digests displayed multiple bands with the DRb, DQb, and DPb probes while the DOb probe hybridized with one to two bands. The RFLP patterns were highly polymorphic but consistent within each DLA-D type. Standard RFLP patterns were established for nine DLA-D types which could be discriminated from each other by using two enzymes (Rsa I and Pst I) and the HLA-DPb probe. Cluster analysis of the polymorphic restriction fragments detected by the DRb probe revealed four closely related supertypic groups or DLA-DR families: Dw3 + Dw4 + D1, Dw8 + D10, D7 + D16 + D9, and Dw1. This study provides the basis for DLA-D genotyping at a population level by RFLP analysis. These results also suggest that the genetic organization of the DLA-D region may closely resemble that of the HLA complex. PMID- 2899547 TI - Duplications and deletions of Vh genes in inbred strains of mice. AB - The evolution of variable region (Vh) gene family copy number and polymorphism was investigated by the analysis of the immunoglobulin heavy chain variable region (Igh-V) locus in 74 inbred strains and substrains of mice. Several strains were found to have slight differences from Igh-V haplotypes previously identified, usually involving the gain or loss of one or a few members of a single Vh gene family. These results indicate that the evolution of copy number in the mouse Igh-V locus proceeds largely by the accumulation of incremental changes, reflecting the clustered organization of the mouse Igh-V locus. We have found no evidence of very large or frequent duplication or deletion events indicative of rapid expansion or contraction processes. The existence of one or more particularly large Vh gene families most likely reflects random copy number variation, rather than selection for the amplification of their members. The identification of strains with recombinant Vh gene arrays demonstrates that recombination, both within and between haplotypes, appears to be the predominant mechanism generating the high restriction fragment length polymorphism in the Igh V locus. PMID- 2899548 TI - Limited polymorphism of both classes of MHC genes in four different species of the Balkan mole rat. AB - We analyzed the restriction fragment length polymorphism of class I and class II MHC genes in DNA from 20 individuals belonging to the four different species of the complex of species of Balkan mole rats Spalax leucodon captured at four different localities in Yugoslavia. All populations were tested with four restriction enzymes and one conserved mouse probe for each of the two classes of MHC genes. The probes employed detect either limited polymorphism of class I genes or lack of polymorphic bands containing class II genes. Of the two other subterranean rodents that have been studied, four karyotype forms of the Israeli mole rat show polymorphism in both classes of MHC genes similar to the one found in all other mammals (Nizetic et al. 1985), and the Syrian hamster shows limited polymorphism of class I genes and high polymorphism of class II genes (McGuire et al. 1985). Balkan mole rats belong to a new group in this respect, different from all mammals studied so far, since they apparently show limited polymorphism of both classes of MHC genes. PMID- 2899550 TI - Field trials on the relative efficacy of three repellents against Mansonia mosquitoes. PMID- 2899549 TI - Linked genetic markers of the rabbit kappa light chain are not linked to the Tcr beta chain genes. AB - In order to investigate linkage, we used serum allotypes of the two rabbit C kappa isotypes and restriction fragment length polymorphisms (RFLPs) of the genes for V kappa, C kappa, and T-cell receptor C beta. The inheritance of these genetic markers was studied through backcross and F2 matings. Southern analysis and hybridization of genomic DNA with a C kappa probe detected a 5 kb Pst I fragment linked to expression of the K2bas1 allotype and the presence of the kappa 1bbas gene and a 6.6 kb Pst I fragment linked to the expression of the K1b9 allotype, the presence of the kappa 2bas2 gene and lack of expression of the K2bas1 allotype. A V kappa probe detected a 1.3 kb Eco RI fragment linked to the presence of the kappa 1bbas gene and expression of the K2bas1 allotype. In contrast, the 9 or 14 kb Eco RI RFLP (C beta a or C beta b) detected with a Tcr beta chain probe segregated independently from C kappa allotypes and RFLPs. It has previously been found that C kappa and C beta are also unlinked in man, whereas in the mouse they are linked at a distance of approximately 8 centimorgans. PMID- 2899551 TI - Clonal population structure of encapsulated Haemophilus influenzae. AB - Chromosomal genotypes of 2,209 isolates of the six polysaccharide capsule types of Haemophilus influenzae recovered from human hosts worldwide were characterized by an analysis of electrophoretically demonstrable allelic profiles at 17 metabolic enzyme loci. For 222 representative isolates, restriction fragment length polymorphism patterns produced by digestion of cap region DNA were also determined. With few exceptions, isolates belonging to individual phylogenetic lines or groups of allied lineages identified by multilocus enzyme electrophoresis had characteristic cap region restriction fragment length polymorphism patterns and characteristic combinations of cap region patterns and outer membrane protein types. The occurrence of strong associations of characters and the recovery of isolates with identical genetic properties in widely separated geographic regions and over a 40-year period indicated that the population structure of encapsulated H. influenzae is clonal. Recombination of chromosomal genes, including those mediating capsule synthesis, apparently is not a major factor in the short-term evolution of these pathogenic organisms and, therefore, may be of minor clinical significance. PMID- 2899552 TI - Characterization of the plasmid from Escherichia coli RDEC-1 that mediates expression of adhesin AF/R1 and evidence that AF/R1 pili promote but are not essential for enteropathogenic disease. AB - RDEC-1, an Escherichia coli strain that adheres to rabbit mucosa and causes an attaching, effacing lesion, expresses the pilus adhesin AF/R1 which determines in vitro attachment to rabbit intestinal brush borders. In order to determine the role of AF/R1 pili in the pathogenesis of enteropathogenic diarrhea in rabbits, we localized the genes for AF/R1 expression, constructed an AF/R1- strain, and compared the virulence of the AF/R1+ and AF/R1- strains with particular attention to the development of attaching, effacing lesions. We introduced Tn5 into the 86 megadalton (MDa) conjugative plasmid known to mediate expression of AF/R1 pili and transferred the derivative plasmids into laboratory strain HB101. Transconjugant M5 was found to contain the 86-MDa plasmid from RDEC-1 and to express AF/R1 pili. Pilus expression on M5 was confirmed by reaction with antiserum raised against purified AF/R1 pili and allowed the bacteria to adhere to the rabbit ileum in an in vitro assay. Three Tn5 insertions in the 86-MDa plasmid were obtained which resulted in loss of AF/R1 expression. Part of the plasmid was mapped, including a region necessary for AF/R1 pilus expression. AF/R1- mutant strain M34 was constructed, and its pathogenesis was investigated. M34 produced disease in rabbits but was less virulent than the parent. The characteristic effacing lesions of RDEC-1 and enteropathogenic E. coli developed in the intestine of rabbits infected with either M34 or RDEC-1, although with M34 they were much less frequent and did not involve the small bowel. We conclude that AF/R1 pilus expression is not essential for the attaching, effacing lesion but serves as an accessory virulence factor which promotes an initial interaction of RDEC-1 with normal epithelial cells. PMID- 2899553 TI - CS31A, a new K88-related fimbrial antigen on bovine enterotoxigenic and septicemic Escherichia coli strains. AB - The nature of the common surface antigen of six hemagglutinating and adhesive piliated Escherichia coli strains isolated from diarrheic or septicemic calves was studied. By electron microscopy studies, the E. coli surface antigen designated CS31A was found on bacterial cells and in purified form to consist of thin (2-nm) "fibrillar" fimbriae. E. coli 31A, which was cured of a 105 megadalton plasmid, failed to express CS31A fimbriae, but retained the ability to hemagglutinate and to adhere in vitro on intestinal cells. Conversely, E. coli K 12, harboring the 105-megadalton plasmid originating from strain 31A, produced CS31A fimbriae but was not able to hemagglutinate or adhere on intestinal cells. A single fimbrial subunit of 29 kilodaltons was observed when purified fimbriae from the 105-megadalton plasmid-containing E. coli K-12 strain was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis or eluted by gel filtration after dissociation by 8.5 M guanidium hydrochloride from an S300 Sephacryl column. Western immunoblot analysis and the N-terminal sequence and amino acid composition of CS31A indicate structural and immunological relatedness between CS31A and K88 protein subunits. PMID- 2899554 TI - Rationale for a new triphasic oral contraceptive. AB - The association of progestogen and estrogen with certain undesirable effects led investigators to seek oral contraceptive (OC) formulations containing reduced amounts of both. Evidence is presented from studies of the triphasic regimen of 0.5 mg norethindrone plus 35 micrograms ethinyl estradiol on the first seven menstrual cycle days, 0.75 mg norethindrone plus 35 micrograms ethinyl estradiol the second seven days, followed by 1 mg norethindrone plus 35 micrograms ethinyl estradiol for the final seven days. This OC formulation appears to be highly effective and relatively free of the side effects commonly associated with low dose OC regimens. PMID- 2899555 TI - Update: The biological effects of hormonal contraceptives. Proceedings of a symposium held at the XIth World Congress of Gynecology and Obstetrics. Berlin, West Germany, September 18, 1985. PMID- 2899556 TI - Arteriosclerosis risk in women and the role of oral contraceptive progestins. AB - Recent studies are reviewed to develop a perspective on the risk of arteriosclerotic heart disease occurring in women using various oral contraceptive (OC) formulations and postmenopausal estrogens. Evidence is provided in support of the following points: (1) arteriosclerosis risk increases in women after age 40 at a rate parallel to that in men; (2) arteriosclerosis risk is related to small changes in lipoprotein concentration, specifically LDL, HDL, and a subfraction of HDL, HDL2; (3) OC formulations alter LDL, HDL, and HDL2 concentrations in relation to the relative biologic effects (potency) of the estrogen and progestin components of the oral contraceptive pill, and/or the associated androgenic effect of the progestin component, with estrogen producing putatively favorable changes, and progestin, unfavorable changes; and (4) arteriosclerosis and myocardial infarction (MI) risk in young women using OC steroids is associated with increasing progestin potency, while postmenopausal women experience a reduced MI-related mortality and all-cause mortality, the latter attributable in part to an increase in HDL cholesterol concentrations. CLINICAL IMPLICATIONS: It is presently advisable to screen all subjects for hypercholesterolemia as a general measure, particularly those subjects who are contemplating the use of OCs. This national mandate is important in light of the data from the Lipid Research Clinics Coronary Primary Prevention Trial. This ten year study showed that a 1% reduction in cholesterol yielded a 2% reduction in coronary risk. Therefore, small changes in a patient's lipid profile can have major ramifications later in life. OC steroids should be used with circumspection by women with existing cardiovascular disease risk factors and should be selected so as to minimize potentially adverse effects on lipoprotein physiology. PMID- 2899557 TI - Progestins and carbohydrate metabolism. AB - The effect of hormonal oral contraceptives (OCs) on carbohydrate metabolism depends on the amount of estrogen (ethinyl estradiol or mestranol), type and amount of progestin, formulation of the pill (monophasic, sequential, or triphasic), duration of use, mode of administration (oral v parenteral), and race and genetic predisposition of the user. The progestin megestrol has minimal effect on carbohydrate metabolism but is no longer available due to its carcinogenic effects in beagle dogs. Combination pills with norethindrone and its derivatives (norethindrone acetate, norethynodrel, and ethynodiol diacetate) show moderate impairment of glucose tolerance with definite hyperinsulinemia. The lowest metabolic effect was observed with triphasic formulations. The effect of levonorgestrel depends on the formulation; the highest impairment of glucose and insulin response after oral glucose loading is found in sequential and combined formulations with doses of 50 micrograms ethinyl estradiol, whereas with doses of 30 micrograms ethinyl estradiol only minor effects on glucose tolerance are seen. Few effects were observed while using triphasic preparations. Therefore, to minimize disturbances of carbohydrate metabolism, low-dose formulations and triphasic preparations should be used. PMID- 2899558 TI - Biological activity of oral contraceptives. AB - The synthetic steroid hormones used in oral contraceptives differ in their effects and potencies. Because all low-dose preparations currently sold in the United States contain the same estrogen, the differences among progestin components are of clinical significance. Synthetic progestins may have progestational, estrogenic, antiestrogenic, and androgenic effects; all have antiovulatory effects. Means for measuring the different effects of steroid hormones, ranging from animal assays to human studies, are reviewed. The problems of generalizing from effects of one steroid in an animal system to combination steroids in the human system are emphasized. Our evolving concept of desirable and undesirable effects of progestins is reviewed, the concept of minimal effective dose introduced, and a conclusion suggested from the limited human data available. A plan for the selection of contraceptive steroids for human use is proposed. PMID- 2899559 TI - Lipid, carbohydrate, and androgen metabolism in women using a triphasic oral contraceptive containing norethindrone for one year. AB - A clinical trial was conducted to determine the effects of a norethindrone containing triphasic oral contraceptive, Ortho-Novum 7/7/7, on lipid, carbohydrate, and androgen metabolism in 22 women during 12 cycles of use. Examinations were made in two consecutive cycles before treatment and after 3, 6, 9, and 12 cycles of treatment. Treatment consisted of ethinyl estradiol, 35 micrograms/d for 21 days, together with norethindrone in stepwise-increasing doses of 0.5, 0.75, and 1.0 mg/d, with each dose given for seven days. Only a minimal impact on lipid metabolism was observed during treatment. There were no unfavorable changes in any HDL-related measurement. HDL-cholesterol and alpha levels were not altered in any cycle. The HDL:LDL ratio was not significantly altered during treatment. LDL cholesterol levels were also unaltered during treatment, but there were slight elevations in other LDL-related measurements in some cycles. Total cholesterol, phospholipid, and triglyceride levels were elevated in cycle 9, and triglyceride levels also increased in cycle 3, but no significant changes were observed in these levels at any other sampling times. Carbohydrate metabolism did not change significantly as indicated by mean fasting levels of glucose, insulin, and HbA1c or by levels of these parameters after a glucose load. Changes observed in androgenic parameters indicate the lack of androgenicity. The results of this study demonstrate that Ortho-Novum 7/7/7 use results in a minimal impact on lipid metabolism, no change in carbohydrate metabolism, and no potential for androgenic side effects. PMID- 2899561 TI - Communicating uteri: description and classification of a new type. AB - A case of bicornuate-bicervical communicating uterus with atresia of the right hemicervix is reported. This cannot be included in any of the nine groups of Toaff's classification of uterine malformations proposed in 1984, and should be classified as a new, tenth type. PMID- 2899560 TI - Early endocrine events in induced pregnancies. AB - Progesterone (P) and human chorionic gonadotropin (beta-hCG) levels were measured randomly or serially in 141 single clinical intrauterine pregnancies resulting from treatment of infertility. Seventy (group I) were conceived during spontaneous cycles, 36 (group II) with clomiphene citrate, and 35 (group III) with menotropins (hMG). Each group was subdivided into subgroup A (normal pregnancies) and B (pregnancies ending in abortion). Thirteen percent of patients in group I aborted, 19% in group II, and 31% in group III (P less than .05). The overall mean (+/- SD) P level in group IA was 25.8 +/- 10.3 ng/mL and in group IB, 16.6 +/- 9.9 ng/mL (significantly lower, P less than .001); in group IIA the mean P level was 37.8 +/- 21.9 ng/mL and in group IIB, 22.9 +/- 17.9 ng/mL, again significantly lower (P less than .01). In subgroups IB and IIB, 11 of 16 patients showed early abnormal beta-hCG patterns; these findings suggest defective embryonic development and/or deficient corpus luteum function as the cause of abortion. There was no significant difference between mean P in group IIIA (71.1 +/- 43.7 ng/mL) and IIIB (75.7 +/- 55.9 ng/mL). In group IIIB, the mean "peak" P level of 101.1 +/- 73.6 ng/mL was followed by a mean "nadir" of 35.4 +/- 24.8 ng/mL at 6-9 weeks. In group IIIB, 7 of 11 patients showed normal beta-hCG patterns. Three patients with precipitous P decline aborted karyotypically normal fetuses in spite of normally rising beta-hCG levels and the presence of fetal cardiac activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899562 TI - Infertility in a patient with abnormal spermatogenesis and in utero DES exposure. AB - A young azoospermic patient is described whose spermatogenesis reflected an abnormality of meiosis. A diagnosis of asynapsis of chromosomes during early spermatogenesis was made by cytogenetic examination of a testicular biopsy. Standard histologic examination gave no indication of this abnormality. An incidental history of intrauterine diethylstilbesterol (DES) exposure of the patient was elicited. Attention is called to the dearth of cytogenetic studies of spermatogenesis in DES-treated male progeny and the usefulness in general of meiotic cytogenetic studies for obtaining accurate diagnoses in human infertility. PMID- 2899563 TI - Comparison of semen quality and follicular growth between conception and non conception cycles after artificial insemination by donor using cryopreserved semen. PMID- 2899564 TI - Excretion of estrone-3-glucuronide in urine in spontaneous and induced ovulatory cycles. AB - Response of the ovary to ovulation-inducing agents, such as clomiphene citrate and gonadotropin, was assessed using estimations of urinary estrone-3-glucuronide (E1G) by an ELISA test. Baseline data collected over 58 cycles from regularly menstruating women were used as reference. Further, the pattern of E1G excretion was compared with ultrasound assessment of follicular growth. In ovulatory cycles, a good correlation is seen between follicular growth and follicular function. However, when cystic follicles develop after treatment, the correlation is poor: the follicle increases in size without a corresponding increase in E1G excretion. It is suggested that ultrasound examination and hormonal pattern should be used concurrently to assess the response of the ovary to ovulation inducing agents. PMID- 2899565 TI - Desensitization of both luteal and pituitary function in baboons with nafarelin, a potent LH-RH agonist. AB - Acute responsiveness in vivo of the baboon corpus luteum to a course of twice daily injections of human chorionic gonadotropin (hCG) has been studied with and without concomitant injections of nafarelin, a potent luteinizing hormone releasing hormone (LH-RH) agonist. HCG injection alone caused an acute (1 hour) rise in circulating levels of progesterone (P), confirmed to be a direct effect at the luteal level, since no change in circulating levels of endogenous LH was detected. When hCG was coadministered with a low dose of nafarelin (50 micrograms per injection), circulating levels of LH rose, but the rise in serum P levels was blunted. However, when hCG was coadministered with a high dose of nafarelin (250 micrograms per injection), serum LH levels rose only in response to the first injection and serum levels of P were not elevated, suggesting a desensitization of the pituitary to the LH-RH agonist and of the corpus luteum to the hCG. The profile of luteal P during the luteal phase in response to combined treatment with hCG and nafarelin also reflected these effects, being intermediate between vehicle controls and hCG treatment alone. This first demonstration of a luteal desensitization to gonadotropin by an LH-RH agonist in primates may account for previously noted successful interception of pregnancy in baboons treated with these agents. PMID- 2899566 TI - Technical improvement for ultrasonic study of the endometrium. AB - Ultrasound imaging has evolved technically. Large-aperture, multielement array systems achieve improved spatial, contrast, and temporal resolutions. These advances are useful for detailed study of the endometrium, especially for early detection of neoplastic disease and premalignant risk factors, assessment and management of infertility, monitoring the course of early pregnancy at--and about -the time of implantation and, possibly, for increasing knowledge about symptomatic conditions, such as dysmenorrhea. Referring physicians should be aware of the level of study that instrumentation advances have now made possible. PMID- 2899567 TI - Application of the quantitative sperm immobilization test for follow-up study of sperm-immobilizing antibody in the sera of sterile women. AB - For quantitative estimation of sperm immobilizing antibody, a new assay method was developed and applied to a follow-up study of antibody titers in the sera of sterile women. The 50% sperm immobilization units (SI50) estimated by the quantitative method ranged from 1.2 to 97.3 in the sera from 16 sterile women who showed relatively high antibody activities in the previous semiquantitative sperm immobilization test. When the quantitative antibody titers, SI50, were followed over 3 years in sterile women with the sperm immobilizing antibody, the antibody titers were found to be unstable, and undulated over a period of several months. Therapy consisting of use of a condom seemed to be ineffective in decreasing the antibody titers. PMID- 2899568 TI - A comparison between the hamster egg penetration test and the seminal parameters in men of infertile couples. AB - The zona-free hamster egg penetration test was performed on 74 random consecutive semen samples from men of infertile couples and on 7 men of proven fertility (semen donors). Of these 74 men, 31 had never before delivered a semen sample (Group I), while the remaining 43 had delivered samples before (Group II). The penetration rates were correlated with the parameters of the semen analysis. In Group I, the mean penetration rate was 59%, in Group II, 42%, and among the fertile donors, 52%. No strong correlation was found between hamster egg penetration rates and the various semen parameters. Only the proportion of motile spermatozoa in Group II correlated significantly with the egg penetration test (P less than .05). Differences in methodology make comparison with the results from different laboratories difficult. It is likely that the egg penetration test measures some separate quality of the spermatozoa that may not be clear from the routine semen analysis. The role of the hamster egg penetration test in the investigation of the causes of infertility should be evaluated further. PMID- 2899569 TI - Estrogen formation from cholesterol in rabbit preimplantation blastocysts and corpora lutea in vitro. AB - Rabbit blastocysts and corpora lutea (CL) obtained six days after coitus were incubated with [4-14C]cholesterol. In the CL, the conversion of [4 14C]cholesterol to radioactive progesterone was about twice that to radioactive estrone. On the other hand, in the preimplantation blastocyst, estrone formation from the substrate was far higher than progesterone formation. Both in the blastocyst and CL, [4-14C]cholesterol was least incorporated into estradiol among the steroids identified. It is suggested that steroids biosynthesized in rabbit preimplantation blastocysts and CL are quite different both in quality and in quantity at the time of implantation. PMID- 2899570 TI - Psychoanalysis and Germany: a re-encounter fifty years after Hitler. PMID- 2899571 TI - Chemistry, histochemistry and microscopy of the organic matrix of spicules from a gorgonian coral. Relationship to alcian blue staining and calcium binding. AB - Alcian blue dye normally binds to polyanionic, polymeric substances. Such structures are often associated with calcium binding portions of the organic matrix in calcifying tissues. The organic matrix of spicules prepared from the gorgonian Pseudoplexaura flagellosa (Houttuyn) is alcianophilic. The dye is very tightly bound to the lipoid portion of the insoluble spicule matrix. No acidic substances (sulfated or acidic polysaccharides or phospholipids) were demonstrable in this material, suggesting an unusual but unknown interaction between dye and substrate. On a microscopical basis, inclusion of Alcian blue (or Ruthenium red) is an essential co-requisite to glutaraldehyde fixation. Without the dye the morphological integrity of the spicule is lost on decalcification. The fragmented matrix is still alcianophilic suggesting that the dye may substitute for material solubilized by the decalcifying agents. Examination of post-decalcification supernatants demonstrate that approximately 13% of the matrix is solubilized on demineralization, releasing 93% of the carbohydrate but less than 20% of the protein. Liberated protein takes the form of peptides ranging from 1100-1500 daltons. The composition of these peptides is a function of the demineralizing agent. Acidic demineralizers produce peptides proportionately high in acidic amino acids, that do not bind calcium. Peptides produced by chelator decalcification appear to bind calcium but other evidence strongly suggests that the binding is due to adsorbed chelator rather than by soluble matrix. PMID- 2899572 TI - Hypothesis for prediction of stimulant drug effectiveness utilizing sensory integrative diagnostic methods. PMID- 2899573 TI - Clearing the air. PMID- 2899574 TI - A look at indemnification. Plain talk about who pays. PMID- 2899575 TI - A reassessment of education. PMID- 2899576 TI - Poor resident participation. Who's to blame? PMID- 2899577 TI - Effect of cimaterol on sheep adipose tissue lipid metabolism. AB - Effects of dietary cimaterol (5 mg/kg) on adipose tissue metabolism of wether lambs were studied. Lipogenesis, lipolysis, fatty acid composition and adipocyte size and number were measured. Cimaterol feeding increased lipogenesis; however, this effect was not statistically significant. Insulin (1,000 microU/ml) stimulated lipogenesis of adipose tissue from control sheep. However, this elevated rate was abolished by in vitro cimaterol. Insulin had no stimulatory effect on lipogenesis in cimaterol-fed sheep. Lipolysis was depressed by cimaterol feeding. However, 10(-4) M cimaterol stimulated lipolysis in the adipose tissue from both control and cimaterol-fed sheep. Insulin inhibited stimulated lipolysis in adipose tissue from control sheep but had no effect on the stimulated lipolysis in cimaterol-fed sheep. Mean adipocyte diameter was smaller (from 74 to 70 microns) and adipocyte size distribution also was changed in the cimaterol-fed sheep. Adipocyte number per gram of tissue was not affected by cimaterol. There was a significant increase in percentage of unsaturated fatty acids in adipose tissue from cimaterol-fed sheep. These results indicate that lipogenic and lipolytic responses to insulin and cimaterol in sheep adipose tissue were altered by cimaterol feeding. The carcass fat content decrease in cimaterol-fed sheep may be attributed to the reduction in adipocyte size. PMID- 2899578 TI - Sodium butyrate preserves aspects of the differentiated phenotype of normal adult rat hepatocytes in culture. AB - We have determined that sodium butyrate and, to a lesser extent, dimethylsulfoxide (DMSO) and 3-aminobenzamide (3-AB) preserve aspects of the differentiated phenotype of primary cultures of adult rat hepatocytes. The histone deacetylase inhibitor, butyrate, inhibits the increase in gamma glutamyltranspeptidase (GGT) activity and the decrease in basal tyrosine aminotransferase (TAT) activity normally observed when hepatocytes are cultured under appropriate conditions. The effects of butyrate on GGT and TAT activities are accompanied by parallel changes in GGT and TAT mRNA levels. The poly(ADP)ribose-synthetase inhibitor, 3-aminobenzamide, has effects similar to butyrate on GGT activity and mRNA levels, while both 3-AB and DMSO increase basal TAT activity in cultured hepatocytes. Under appropriate conditions all three agents--butyrate, 3-AB, and DMSO--extend the length of time cultured hepatocytes can be maintained as confluent monolayers. However, under all the conditions studied, butyrate extended the length of time hepatocytes could be maintained as monolayers more than any other treatment used. Butyrate-treated hepatocytes maintained ultrastructural features that were more similar to those of hepatocytes in vivo than hepatocytes treated with any other of the agents tested. Histone acetylation levels of primary cultures of adult rat hepatocytes declined concomitant with the loss of the differentiated phenotype of the cells. These results suggest that histone acetylation may play a role in the changes in gene expression observed when hepatocytes are placed in culture. PMID- 2899579 TI - Research on psychotherapy integration: recommendations and conclusions from an NIMH workshop. PMID- 2899580 TI - Privatisation and other problems. PMID- 2899581 TI - Epidemiological typing: a user's view. PMID- 2899583 TI - Prior antimicrobial therapy and resistance of Enterobacter Citrobacter and Serratia to third generation cephalosporins. AB - During a 6-month period all inpatients from whom Enterobacter, Citrobacter or Serratia. had been isolated were reviewed and information on selected variables recorded. Two groups, one including 19 patients with organisms resistant to third generation cephalosporins and the other 111 patients with susceptible organisms were compared. In the initial analysis, the mean number of antimicrobials received in the prior 2 months was the variable most strongly associated with isolation of resistant organisms (2.6 +/- 1.5 vs 1.5 +/- 1.6; P = 0.002). When patients who had received no antimicrobials were omitted from the analysis, the mean number of antimicrobials was similar (2.6 +/- 1.5 vs 2.3 +/- 1.5; P = 0.19). Comparisons of antimicrobials received in the prior 2 months showed only cefoxitin (9/70 vs 7/19; P = 0.016) and cefotaxime (4/70 vs 5/19; P = 0.008) to be associated with isolation of resistant organisms. These data suggest that, at our institution, antimicrobial therapy with an extended spectrum cephalosporin is an important risk factor for subsequent acquisition of an organism resistant to third generation cephalosporins. PMID- 2899582 TI - A comparison of the effects of preoperative whole-body bathing with detergent alone and with detergent containing chlorhexidine gluconate on the frequency of wound infections after clean surgery. The European Working Party on Control of Hospital Infections. AB - In a prospective, randomized, double-blind, placebo-controlled study involving 27 surgical units in six European countries, the effect of preoperative whole-body bathing on two occasions with a detergent containing chlorhexidine (CHX+) on the incidence of wound infection in elective, clean surgery was compared with two bathings with a detergent without chlorhexidine (CHX-). In the CHX+ group 2.62% of 1413 patients and in the CHX- group 2.36% of 1400 patients subsequently became infected. The infection rate in the CHX+ group was 1.11 times that in the CHX- group with 95% confidence limits ranging between 0.69 and 1.82. Consequently, bathing patients twice preoperatively with chlorhexidine-detergent did not reduce the incidence of infection of clean wounds. PMID- 2899584 TI - National prevalence survey of hospital-acquired infections in Czechoslovakia. AB - A nationwide 1-day prevalence survey of a total of 12,260 patients in 23 hospitals across Czechoslovakia yielded 751 cases of hospital-acquired infection (HAI), a prevalence of 6.1%. Analysis of the data revealed that the prevalence of HAI amongst surgical patients was almost twice that amongst medical patients (8.2% vs. 4.4%). Persons aged over 60 on the urological and surgical wards were at highest risk of acquiring infection. The most frequent site of HAI was the urinary tract (25%), followed by surgical wounds (15%) and the upper respiratory tract (13%). Fifty per cent of infection in gynaecological patients occurred within 6 days of admission compared with 15% in urological patients, and a wide variation was seen in other specialties. PMID- 2899585 TI - Gastrointestinal carriage rate of Clostridium difficile in elderly, chronic care hospital patients. AB - The carriage rate of Clostridium difficile in patients at a chronic care hospital was determined by two point prevalence surveys at 6-monthly intervals. In the first survey C. difficile or its toxin was present in stool samples from five symptomless patients on three of the four wards studied. All of these colonized patients had been in hospital for at least 2 months, but there was no relationship between carriage of the organism and antibiotic use. When the survey was repeated 6 months later, no symptomless carriers were found but one symptomatic patient had C. difficile and its toxin present in the stool. The results suggest that C. difficile should always be considered as a possible cause of diarrhoea in long-stay hospitalized patients. PMID- 2899587 TI - Influence of age on faecal carriage of P-fimbriated Escherichia coli and other gram-negative bacteria in hospitalized neonates. AB - The aerobic faecal flora of 953 infants aged over 5 days was studied on discharge from 22 neonatal wards in Swedish hospitals. Klebsiella/enterobacter was isolated from 74% of infants and dominated the aerobic gram-negative flora in 19 wards. Escherichia coli was carried by 42% and showed a slight dominance in two wards. Initially klebsiella/enterobacter dominated the flora but became increasingly mixed with and taken over by E. coli, carriage increasing from 21% in infants discharged after 5-7 days to 57% after 3 weeks or later. Among infants with E. coli, P-fimbriated strains were demonstrated in 23% (range 0-67) and were independent of age. Occasional clustering of such strains was observed in 3/22 wards during the study period. It is postulated that the general and local colonization patterns observed reflect differences between individual strains of E. coli and klebsiella in both their capacity for transmission and their persistence in the newborn gut. The role of P-fimbriae in intestinal colonization of neonates by E. coli was, however, not supported. PMID- 2899586 TI - A multicentre study to compare piperacillin with the combination of netilmicin and metronidazole for prophylaxis in elective colorectal surgery undertaken in district general hospitals. AB - We have conducted a multicentre randomized study to compare piperacillin with the combination of netilmicin and metronidazole in patients undergoing elective colorectal surgery. There was no significant difference in the incidence of operation-related infection, chest or urinary tract infection. Major life threatening sepsis occurred in 6% and the overall incidence of operation-related infection was 24%. Organisms which normally inhabit the bowel lumen were cultured from most of the postoperative infections; however, Staphylococcus aureus was isolated as a causative organism in nine patients in the piperacillin group compared with none in the netilmicin and metronidazole group. We are concerned at the high incidence of infection in both groups, and we believe that other factors in addition to prophylactic antibiotics need to be evaluated if the incidence of infection is to be reduced further. PMID- 2899588 TI - A prospective randomized controlled trial of perioperative antibiotic prophylaxis in renal transplantation. AB - We have carried out a prospective, randomized controlled trial of perioperative prophylaxis with cefuroxime and piperacillin in 53 recipients of renal allografts. Twenty-seven patients received antibiotic prophylaxis with three doses of cefuroxime 750 mg and piperacillin 4 g, and 26 patients received no prophylaxis. Risk factors for infection were well matched. Infection rates were analysed for the periods 0-5 days and 0-14 days post-transplant. In the first 5 days, patients receiving antibiotics had fewer infections (3 vs. 11, P = 0.04) but by 14 days this difference was no longer apparent (21 vs. 30, P = NS). There was a total of 15 wound infections, which were more common in the control group both at 5 days (1 vs. 5, P = NS) and at 14 days (4 vs. 11, P = 0.027). Urinary infections were unaffected by prophylaxis. We conclude that perioperative antibiotic prophylaxis results in a modest but worthwhile reduction in the incidence of wound infections after renal transplantation. PMID- 2899589 TI - The effect of handling procedures on microbial contamination of enteral feeds. AB - Three of the most commonly used delivery systems in enteral feeding were evaluated for potential routes of contamination during assembly and delivery of feeds. Assembly of systems wearing sterile gloves gave no contamination in the feeds but all systems were contaminated when assembled either with bare unprotected hands or with hands experimentally contaminated with bacterial cells. Delivery of contamination-free feed was only possible with the use of sterile gloves. PMID- 2899590 TI - Short-term cephradine prophylaxis in elective transurethral prostatectomy. AB - A prospective randomized trial was conducted to assess the value of short-term antibiotic prophylaxis in elective transurethral resection of the prostate. Two hundred patients were randomized to receive 1.5g cephradine intramuscularly preoperatively and 1g cephradine orally before removal of the urethral catheter or to receive no antibiotic prophylaxis. Fifty-eight patients were excluded because of occult neoplasm or protocol violation. There was no difference in time to removal of catheter, incidence of pyrexial episodes, length of hospital stay or minor complication rate between the two groups. We conclude that a short-term antibiotic regime is of no value in the elective patient with sterile urine. PMID- 2899591 TI - Assessment of 'cold Sterilog glutaraldehyde monitor'. AB - A new monitor, used in conjunction with an ultraviolet spectrophotometric difference method to determine glutaraldehyde concentration was tested with 2% alkaline solutions of varying concentrations and pH. Glutaraldehyde solutions with a concentration below 1.6% were rejected by the monitor, which reflected deterioration of glutaraldehyde quite closely, but failed to yield satisfactory results with fresh 2% alkaline solutions. PMID- 2899592 TI - Current problems with methicillin-resistant Staphylococcus aureus. PMID- 2899593 TI - The prevention and control of superficial wound infection in a military training establishment: a comparative study of two different strengths of povidone-iodine dry powder spray. PMID- 2899594 TI - MIC tests are not suitable for assessing antiseptic handwashes. PMID- 2899595 TI - Unusual pathogens in neutropenic patients. PMID- 2899597 TI - Thymocyte subpopulations during early fetal development in the BALB/c mouse. AB - Phenotypic analysis of thymocytes during murine fetal development may be of use in determining the pathways of thymocyte differentiation. The expression of the functionally significant molecules Lyt-2 (CD8), L3T4 (CD4), and the TCR has already been described. However, mAb specific for several other murine lymphocyte surface markers are now available and, although these have been used to characterize adult thymocytes, a detailed analysis of fetal thymocytes with these antibodies has not previously been undertaken. In this study, we have used mAb specific for Thy-1, J11d, Pgp-1, and the IL-2R, in addition to those for Lyt-2 and L3T4, to identify subpopulations of early fetal thymocytes. By using two color flow cytometric analysis of cells obtained from fetal thymuses on sequential days of gestation, we have been able to follow the development of various subpopulations through early fetal ontogeny. Our data indicate that the earlier thymocytes are found in the J11d+/Pgp-1+ subset which is abundant at fetal day 14 but constitute a numerical minority by day 16. PMID- 2899596 TI - CD11a-c/CD18 and GP84 (LB-2) adhesion molecules on human large granular lymphocytes and their participation in natural killing. AB - Effect of mAb against the CD11a-c, CD18, and GP84 adhesion molecules on the binding and cytotoxicity of human NK cells was studied. The target cells were K562, MOLT-4, Raji, and fresh uncultured autologous endometrial carcinoma cells. Antibodies against adhesion relevant epitopes of CD11a(TA-1/LFA-1), CD11b(Mol/OKM1/Mac1), or CD11c (Leu-M5) did not inhibit NK function. The mAb 60.3 against CD18, the common beta-chain associated to CD11a-c, strongly inhibited both the binding and cytotoxicity of large granular lymphocytes (LGL) against all the target cells tested. Also the antibody LB-2 against the GP84 adhesion molecule inhibited NK function to some degree. 60.3 and LB-2 antibodies exerted an additive effect in the inhibition of both binding and cytotoxicity. However, even this antibody combination did not completely block NK activity, suggesting a heterogeneity of adhesion structures in the NK system. According to both FACS analyses and immunoprecipitation studies, all the tested antibodies recognized either a subpopulation or all of LGL. On the other hand, antibodies against CD11b, CD11c, and LB-2 showed only marginal reactivity with highly purified LGL free T cells. PMID- 2899599 TI - Human T lymphotropic virus I infection deregulates surface expression of the transferrin receptor. AB - Human T-lymphotropic virus I (HTLV-I) is an etiologic agent in adult T cell leukemia. In an effort to understand the relationship between HTLV-I infection and malignant transformation, we have examined transferrin receptor expression in HTLV-I-infected cells. Transferrin receptor expression in normal T cells is tightly regulated and essential for cell proliferation. We have used matched T cell sets originating from a normal donor, consisting of tetanus toxoid-specific normal T cell clones (TM3 and TM5) and their in vitro HTLV-I-infected counterparts (TM3H and TM5H). Using these matched sets of virus-infected and normal T cells, we have determined that HTLV-I infection leads to hyperexpression of surface transferrin receptors (five- to six-fold higher than normal counterparts). Although the growth rates of the virus-infected cells did not differ significantly from their normal controls, HTLV-I-infected cells constitutively hyperexpressed surface transferrin receptors, whereas the level of surface receptor expression of normal counterpart cells varied during the cycle of antigenic stimulation. Immunoprecipitation of total (surface plus cytoplasmic) transferrin expression showed that the HTLV-I-infected cells did not possess a greater total number of transferrin receptors than their normal counterparts. This data was supported by Northern blot analysis, which showed equivalent transferrin receptor mRNA expression in HTLV-I-infected and uninfected cells. Functional analysis revealed a marked defect in 59Fe-transferrin internalization in the HTLV-I-infected cells. Furthermore, the HTLV-I-infected cells showed markedly decreased transferrin receptor phosphorylation and internalization in response to active phorbol ester. Thus the data demonstrate that in peripheral blood T cells, HTLV-I infection is accompanied by surface transferrin receptor overexpression secondary to subcellular redistribution and defective internalization. PMID- 2899598 TI - The murine IgA-secreting plasmacytoma MOPC-315 expresses somatostatin receptors. AB - We have previously shown that some neuropeptides had a profound effect on in vitro Ig synthesis (especially IgA) and mitogen-driven murine lymphocyte proliferation. MOPC-315, an IgA-secreting plasmacytoma line, has been extensively used in studies of the regulation of IgA synthesis. In this report we show that the neuropeptide somatostatin (SOM) inhibits proliferation ([3H]thymidine uptake) of MOPC-315 and also inhibits IgA synthesis in vitro. MOPC-315 cells bind both fluorescent SOM and [125I]SOM specifically. On cytofluorimetric analysis, 68 +/- 6.8% (mean +/- SE, n = 7) of MOPC 315 cells labeled with fluorescent SOM and this staining was compatible by incubation with an excess of unlabeled peptide. Specific [125I]SOM binding increased linearly with cell concentration, was rapid and achieved equilibrium after 20 min at 4 degrees C. It was temperature dependent, readily reversible, and under equilibrium conditions demonstrated a dissociation constant of 1.6 +/- 0.7 nM (mean +/- SE, n = 5). Scatchard analysis showed that MOPC-315 cells had 40,733 +/- 16,050 (mean +/- SE) binding sites for SOM per cell. The characteristics of the interactions of SOM with MOPC-315 cells suggest a specific receptor-mediated mechanism whereby this neuropeptide may modulate lymphocyte function. PMID- 2899600 TI - Activation of MHC-restricted rat T cells by cloned syngeneic thyrocytes. AB - We have previously demonstrated that rat thyrocytes express MHC class II Ag (RT1.B&D) in response to IFN-gamma. To determine whether MHC class II-positive thyrocytes can be recognized by MHC-restricted T cells, we used our clone of rat thyroid cells (1B-6) derived from the Fisher rat thyroid cell line (FRTL-5) and known to express MHC class II Ag in response to recombinant rat IFN-gamma. CD4+ and CD8+ normal syngeneic Fisher rat spleen T cells were selected by flow cytometry and averaged greater than 96% purity. We demonstrated that irradiated MHC class II-positive but not class II-negative 1B-6 thyrocytes stimulated CD4+ T cells in a primary sensitization reaction over 4 days. In contrast, CD8+ T cells had no response in similar experiments. This stimulation of CD4+ T cells was dose dependent for 1B-6 thyrocytes and was abrogated by anti-rat MHC class II mAb (MRC OX-6). Autoreactive (Fisher) and alloreactive (Buffalo) T cell lines and isolated CD4+ T cells derived from these lines, which were developed against Fisher rat spleen cells, similarly recognized MHC class II Ag expressed on 1B-6 cells but had no detectable response to 1B-6 MHC class II-negative thyrocytes or MHC class II-positive human thyroid cells. The CD4+ T cell recognition of 1B-6 cells via MHC class II Ag supports our previous data with autologous human thyroid T cell co-cultures and is indicative of an autospecific role for thyrocytes in the development of autoimmune thyroiditis. PMID- 2899601 TI - Expression of the J11d marker on peripheral T lymphocytes of MRL-lpr/lpr mice. AB - MRL-lpr/lpr (lpr) mice spontaneously develop massive lymphadenopathy resulting from the expansion of a unique population of Thy-1+ cells which are CD4- and CD8- (double negative) and the nature of which is not clear. The antibody J11d has been shown to define a differentiation Ag found on immature thymocytes but not on mature and functional peripheral CD4+ or CD8+ T cells. To analyze the possible relationship between the lpr double-negative T cells and the thymocytes, we investigated the simultaneous expression of J11d and Thy 1 Ag on the double negative lpr lymph node cells by using two-color immunofluorescent staining technique. We observed that lpr mice at 3 to 4 weeks of age, before the onset of lymphadenopathy, did not have significant numbers (less than 4%) of J11d+ T cells in the periphery, similar to the number found in the control MRL +/+ mice. However, with increasing age of approximately 8 to 10 weeks and coinciding with the appearance of lymphadenopathy, a significant number (approximately 35%) of J11d+ Thy-1+ cells started appearing in the periphery of lpr mice and was maintained until the mice died at 20 to 24 weeks of age. The J11d+ T cells belonged to the abnormal double-negative T cell pool, inasmuch as J11d+ CD4+ or J11d+ CD8+ cells were absent in the lymph nodes of 20-wk-old lpr mice. Furthermore, 20-wk-old lpr mice demonstrated increased numbers (approximately 41%) of double-negative T cells in the thymus, a significant proportion of which were J11d+. In contrast, the 20-wk-old +/+ mice or 4-wk-old lpr mice had only 4% double-negative T cells in the thymus. The present study suggests that a significant number of peripheral double-negative T cells of lpr mice bear the immature thymic differentiation Ag J11d. The possibility that the accumulation of double-negative T cells results from abnormal peripheralization of double negative J11d+ thymocytes, before complete differentiation into CD4+ or CD8+ T cells, is discussed. PMID- 2899602 TI - IL-2 production in human T lymphotropic virus I-infected leukemic T lymphocytes analyzed by in situ hybridization. AB - In situ hybridization studies were performed with 35S-labeled anti-sense RNA probes to study IL-2 mRNA expression in three human T lymphotropic virus I infected T cell lines at the single cell level. In HuT 102, MT-2, and MT-4 cells, IL-2 mRNA-expressing cells were identified, occurring at frequencies of 2 x 10( 2), 8 x 10(-3), and 5 x 10(-3), respectively. In these cell lines, IL-2 mRNA was not detectable in RNA extracted from whole adult T cell leukemia cell populations because of dilution by other RNA species from the vast majority of cells that do not contain IL-2 mRNA. The data indicate the possibility of paracrine growth stimulation via IL-2 and its receptor even in those human T lymphotropic virus I infected T cell populations that apparently lack IL-2 activity when analyzed by conventional assay procedures. PMID- 2899603 TI - Idiotype vaccines against human T cell leukemia. II. Generation and characterization of a monoclonal idiotype cascade (Ab1, Ab2, and Ab3). AB - Previously, we had generated anti-Id mAb (Ab2) binding to a hybridoma SN2 (Ab1), which recognizes a glycoprotein, gp37, expressed by human leukemic T cells. To characterize these anti-idiotopes further, they were used to immunize mice and rabbits. Several murine anti-anti-Idiotype mAb (Ab3), mostly of IgM-k isotype, were obtained. mAb3 and sera from rabbits immunized with Ab2 contained antibodies that bind to gp37 Ag and leukemic MOLT-4 and JM cells. Also, mAb3 and immune sera from rabbits competed with Ab1 for binding to MOLT-4 cells. They inhibited the binding of iodinated Ab1 to Ab2 indicating that Ab3 in mice and rabbits shares idiotopes with Ab1 (SN2). Furthermore, both the murine mAb3 and rabbit polyclonal Ab3 immunoprecipitated the same gp37 Ag as SN2 (Ab1). The production of Ag specific Ab3 (Ab1') in mice and rabbits in absence of any exposure to gp37 indicates that these Ab2 may indeed carry the internal image of the gp37 Ag. Such anti-idiotopes (Ab2 beta) may be useful as Ag substitute for the induction of therapeutic immunity in T cell leukemia patients. PMID- 2899604 TI - Beta-adrenergic agonists blocked the expression of IL-2 receptors on mitogen stimulated lymphocytes and IL-2-dependent T cell lines. PMID- 2899605 TI - Comparative study of intravenous metronidazole and intramuscular dehydroemetine in amoebic liver abscess. PMID- 2899606 TI - The dose-response for low-LET radiation-induced DNA double-strand breakage: methods of measurement and implications for radiation action models. AB - There is considerable controversy over the form of the dose-response for DNA double-strand breakage (dsb) induction in mammalian cells by low-LET type radiation. This controversy centres on the techniques used for measuring DNA dsb. The applications and shortcomings of the four major techniques for estimating DNA size--sedimentation, viscoelastometry, electrophoresis, and non-denaturing filter elution--are examined. In particular, the criticisms of the results obtained using the non-denaturing filter elution technique, which have suggested that the DNA dsb dose-response is non-linear, are discussed. It is concluded that these results may require a re-evaluation of the basic assumptions of many radiation action models. PMID- 2899607 TI - Cell proliferation in the murine epidermis and subcutaneous vascular endothelium after hyperthermia. AB - The skin of mouse legs was exposed to 44 degrees C hyperthermia using a thermostatically controlled waterbath. Treatment at 44 degrees C, for 15 or 30 min, led to oedema in the dermis immediately after treatment and to an infiltration by neutrophils within 7 h. The oedema disappeared in 2 days. Treatment for 60 min at 44 degrees C led to subepidermal blistering and as a result of this a considerable area of the tissue became necrotic 4 days after treatment. A repair reaction followed, and 3 weeks after heating for 60 min at 44 degrees C the epithelium was again completely or almost completely covering the underlying tissue. Shortly (7 h) after 15 or 30 min at 44 degrees C an increase was observed in the number of basal cells in the epithelium incorporating [3H]thymidine. This increase declined slowly with time: 3 weeks after treatment the number of labelled basal cells was not significantly different from that in untreated skin. Shortly after 60 min at 44 degrees C some basal cells of the epidermis still incorporated [3H]thymidine. The labelling index dropped to near zero at day 2 after 60 min at 44 degrees C. Thereafter repopulation started and in the areas next to the granulation tissue the labelling index of basal cells reached values close to 100 per cent, 2 or 3 weeks after treatment. Treatment for 15 min at 44 degrees C did not lead to a stimulation of the proliferation of subcutaneous endothelial cells. Both 30 min and 60 min at 44 degrees C led to a greatly enhanced proportion of labelled subcutaneous endothelial cells after 2 days and 4 weeks, respectively (labelling index between 35 and 40 per cent). After this peak value the labelling index declined rapidly. However, in granulation tissue it remained high for about 10 days after the peak on day 4. The stimulated proliferation of subcutaneous endothelial cells after heating for 30 and 60 min at 44 degrees C correlated well with the finding that these heat treatments, given after or shortly before X-irradiation, led to a greatly reduced (X-ray-induced) tumour bed effect. PMID- 2899608 TI - SEM autoradiography: aggregation of inhaled 239PuO2. AB - Aggregation of inhaled 239PuO2 particles in the pulmonary region of the lung may be required for promotion of pulmonary carcinogenesis in rats. Female Wistar rats were exposed to an aerosol of 239PuO2 and their lungs examined by scanning electron microscopic (SEM) autoradiography. SEM autoradiography provides a rapid and inexpensive method for viewing a large lung tissue volume for alpha tracks. Evidence of particle aggregation was seen by 28 days postinhalation and was marked by 90 to 150 days post-inhalation. Subpleural plutonium particles resulted in exposure into the pleural cavity. Peribronchiolar, alveolar plutonium particles and particle aggregates gave the greatest radiation dose to the bronchiolar epithelium. High-dose, overlapping, alpha-track, radiation zones in bronchiolar epithelium may be required for maximum development of lung tumors. PMID- 2899609 TI - Oxidation of iodide by the intense acoustic bursts of an extracorporeal lithotripter. PMID- 2899610 TI - Does incomplete repair explain the apparent failure of the basic LQ model to predict spinal cord and kidney responses to low doses per fraction? AB - Recent evidence indicates that isoeffect doses for spinal cord and kidney may be overestimated for fraction sizes as small as 1 or 2 Gy when calculated from a linear-quadratic (LQ) model fitted to data obtained for fraction sizes larger than 2 Gy. Reasons for this are unknown, but possible interpretations include exhaustion of repair capacity and incomplete repair in experiments designed to study the response to these small doses. The latter interpretation is motivated by the relatively short intervals between multiple daily doses given to the spinal cord (4 h) and kidney (5 h) when fraction sizes were small. The possibility that overestimation of isoeffect dose could be explained by incomplete repair during short intervals between doses was assessed by fitting experimental data to the incomplete-repair model. For the spinal cord the data could be interpreted by assuming that a repair process with a half-time of 1.7 h was incomplete; this half-time is negligibly different from the estimate obtained from repair-kinetics experiments with larger doses per fraction. The deviation from the (complete-repair) LQ model could be interpreted for the kidney in terms of a half-time of repair of 2.8 h (a negligibly different fit was obtained with the value 1.5 h). The clinical implication could be that multiple-fractions-per day treatment would benefit from use of the longest feasible interfraction interval when late reactions are dose limiting. PMID- 2899611 TI - Combined action of phthalocyanine photosensitization and gamma-radiation on mammalian cells. AB - The response of Chinese hamster cells and human lymphocytes to the combined action of photosensitization by chloroaluminium phthalocyanine tetrasulfonate and gamma-radiation was studied using colony-forming ability and [3H]thymidine incorporation following mitogenic stimulation respectively, as endpoints. The action of both treatments was usually additive regardless of the sequence of application. However, in human lymphocytes irradiated at low temperature, the photosensitization interacted synergistically with the subsequent ionizing radiation; in this experiment the initial photosensitization reduced the yield of micronuclei produced by gamma-radiation. PMID- 2899612 TI - Relationship between sedimentation behaviour of DNA-protein complexes and DNA single- and double-strand breaks after irradiation with gamma-rays, pulsed neutrons and 12C ions. AB - The sedimentation behaviour of DNA-protein complexes was studied following irradiation of Chinese hamster cells (V79-4) and human lymphocytes over a wide dose range of 137Cs gamma-rays, pulsed neutrons and accelerated 12C ions. We have shown that the decrease of relative sedimentation velocity of the complexes at low doses is related to the occurrence of single-strand breaks in DNA. Rejoining of the breaks during a repair period increases the sedimentation velocity. At higher doses of radiation, double-strand breaks lead to an increase of sedimentation velocity of DNA-protein complexes. A new method can be devised on the basis of these results enabling estimation of the yields of single- and double-strand breaks in DNA. PMID- 2899614 TI - Radiosensitive xrs-5 and parental CHO cells show identical DNA neutral filter elution dose-response: implications for a relationship between cell radiosensitivity and induction of DNA double-strand breaks. AB - The purpose of this work was to investigate a possible correlation between DNA elution dose-response and cell radiosensitivity. For this purpose neutral (pH 9.6) DNA filter elution dose-response curves were measured with radiosensitive xrs-5 and the parental Chinese hamster ovary (CHO) cells in the logarithmic and plateau phase of growth. No difference was observed between the two cell types in the DNA elution dose-response curves either in logarithmic or plateau phase, despite the dramatic differences in cell radiosensitivity. This observation indicates that the shape of the DNA elution dose-response curve and the shape of the cell survival curve are not causally related. It is proposed that the shoulder observed in the DNA elution dose-response curve reflects either partial release of DNA from chromatin, or cell cycle-specific alterations in the physicochemical properties of the DNA. PMID- 2899613 TI - Unusual alkaline elution pattern induced in mammalian cell DNA by fast neutrons p(34) + Be. AB - Syrian hamster fibroblasts (cell line BHK 21/13) were exposed to p(34) + Be fast neutron irradiation and their DNA analysed by the alkaline elution technique. The elution profiles showed an unusual tailing off, characteristic of neutron irradiated samples, suggesting the presence of a modification in DNA induced by the neutrons. This was not seen with 60Co gamma-irradiation. In neutron irradiated samples the alteration of DNA appeared to persist even after 2 h of post-treatment incubation (37 degrees C) indicating the absence of repair. The modification of DNA induced by neutrons provides a possible explanation for the reduction of the shoulders in survival curves obtained with neutrons, and the high RBE of neutrons. PMID- 2899615 TI - Critical DNA target size model of ionizing radiation-induced mammalian cell death. AB - A new model of mammalian cell killing by ionizing radiation is presented. This model, termed the critical DNA target size model, postulates that DNA double strand breakage is the critical radiation-induced lesion and that the dose response for such breakage can be non-linear due to the action of a saturable chemical repair process. DNA double-strand breakage occurring within critical targets (proto-oncogene- or common fragile site-associated sequences) is postulated to initiate recombination events with undamaged sequences, leading to chromosomal aberrations. The subsequent loss of acentric fragments at mitosis is postulated to prevent the continuity of the genome and to produce cell death by the induction of chromatin structural changes. Experimental evidence contrary to other radiation action models is examined, and the hypotheses of the model are justified. PMID- 2899616 TI - Effect of X-ray dose protraction and a tumor promoter on transformation induction in vitro. AB - We have investigated the effects of X-rays given in a brief exposure (1 min or less) or protracted over 5 h, on cell survival and the induction of neoplastic transformation in C3H/10T1/2 cells with an emphasis on latent transformation damage remaining after protracted irradiation. This latent damage and its expression were investigated at accumulated doses of 0.25 to 4 Gy by chronic treatment with TPA (12-O-tetradecanoyl-phorbol-13-acetate or phorbol myristate acetate) at 0.1 microgram/ml beginning after irradiation. Transformation incidence from protracted as well as brief X-irradiations was linearly related to X-ray dose in the presence of 0.1 microgram/ml TPA/ml. In the absence of TPA, the best fits were obtained with cubic rather than quadratic functions. The effect modifying factors due to dose protraction were similar with or without TPA and averaged 4.6 at low doses (up to 2 Gy). Also within this dose range average transformation enhancement due to TPA was approximately 4. Our results indicate that dose protraction does not change the shape the dose-response curve for transformation, and that the shape change induced by TPA is also independent of dose protraction. PMID- 2899617 TI - Cure, cell killing, growth delay and fragmentation of X-irradiated human melanoma HMV-I multicellular spheroids. AB - Human melanoma, HMV-I, multicellular spheroids were irradiated and cure was determined by the absence of cellular outgrowth. Their cellular radiosensitivity was measured by the colony-forming ability of cells dispersed from the spheroid. Analysis of radiocurability of spheroids in terms of their cellular radiosensitivity predicted three necessary conditions: a linearity of dose versus the double-minus logarithm of curability; constancy of a critical cell number; and constancy of cellular radiosensitivity. These conditions were found to exist in the observed data for each of three size classes of spheroids. Analysis suggests that cellular radiosensitivity in multicellular spheroids with diameters of 250 and 400 microns was different from that of monolayers, and that the increase of spheroid-control doses was found to be a function of cellular radiosensitivity, total cell number per spheroid and a critical cell number. The critical cell number increased from 0.8 in a 150 microns spheroid to 4 in a 250 microns spheroid and to 57 in 400 microns spheroid. This number is a unique characteristic of multicellular systems and is one important factor in determining their radiocurability. X-ray-induced growth delay of spheroid size was increased with increasing dose. At high doses a sharp increase in delay time was seen, sometimes accompanying fragmentation of spheroids at late postirradiation times. The clonogenic activity of these fragments may serve as a model of exfoliation, the first step of radiation-induced metastasis. PMID- 2899618 TI - Polyarteritis nodosa: report in a newborn infant. PMID- 2899619 TI - Split tolerance induced by the intrathymic adoptive transfer of thymocyte stem cells. AB - The intrathymic transfer of semiallogeneic CD4/CD8 double-negative (DN) thymocyte stem cells into irradiated host mice resulted in a transient state of chimerism in adoptive host thymus, spleen, and lymph nodes. Host-derived T cells, isolated from the thymus and periphery of the chimeric mice, were found to be specifically nonresponsive to the MHC antigens of the semiallogeneic DN donor in cytotoxicity assays. This nonresponsiveness was not permanent, but persisted as long as appreciable numbers of Thy-1 alloantigen-positive progeny of the DN donor cells could be detected in the spleen and lymph nodes of adoptive host mice. FACS sorting of DN donor cells before intrathymic transfer indicated that nonresponsiveness could be induced by Thy-1+ cells and was therefore not attributable to contaminating thymic macrophages, dendritic cells, or B cells. When FACS-sorted Thy-1+ (bm5 x bm12)F1 DN cells were transferred intrathymically into C57BL/6 hosts, nonresponsiveness to DN donor MHC class I but not class II alloantigen (split tolerance) was observed. These experiments were repeated using FACS-sorted Thy-1+ DN donor cells that were semiallogeneic to the irradiated adoptive host at either MHC class I or class II locus with similar results. Limiting dilution analysis showed that host-derived CTL precursors were tolerant of DN donor MHC class I alloantigen and no evidence for the involvement of suppressor T cells was found. The data indicate that murine thymocytes themselves are capable of tolerizing to MHC class I but not class II alloantigen after intrathymic transfer. The implications for intrathymic T cell differentiation and maintenance of self tolerance are discussed. PMID- 2899620 TI - Receptor analogs and monoclonal antibodies that inhibit adherence of Bordetella pertussis to human ciliated respiratory epithelial cells. AB - The adherence of Bordetella pertussis to human respiratory cilia is critical to the pathogenesis of whooping cough. To explore the development of agents that could interrupt adherence, the structure of the receptor on the ciliary surface was investigated. Using an in vitro adherence assay to human ciliated epithelial cells, galactose, lactose, and complex carbohydrates containing lactose eliminated adherence when preincubated with the bacteria. 10(-2) M galactose eluted adherent bacteria from cilia. B. pertussis and its two purified adhesins bound specifically to natural lactose-containing glycolipids in a TLC assay. mAbs to eukaryotic glycoconjugates with specificity for substituted galactose-glucose moieties blocked adherence when preincubated with ciliated cells. The carbohydrates that serve as receptors for B. pertussis on human cilia are galactose-glucose-containing glycolipids. Receptor analogs and anti-receptor antibodies effectively block adherence of B. pertussis to cilia and thus should be considered candidates for therapeutic intervention against disease. PMID- 2899621 TI - Nonnutritive sucking in tube-fed preterm infants: effects on gastric motility and gastric contents of somatostatin. AB - The present study investigated the way that sucking of a pacifier influences gastric secretory and motor functions in connection with tube feeding. Experiments were performed on eight preterm infants who were tube fed twice--once with and once without sucking of a pacifier. The time for tube feeding was significantly decreased and gastric retention decreased in five of seven infants when sucking a pacifier. Maternal milk was found to contain gastrin-17, somatostatin-14, and a somatostatin-like peptide larger than somatostatin-28. Somatostatin levels were significantly reduced in connection with non-nutritive sucking. Gastrin levels were increased in six of ten experiments 2 h and/or 3 h after bolus feeding, suggesting that these peptides were not only supplied by the milk, but were also released from the gastric mucosa. The presence of gastrin and somatostatin in gastric aspirates was established by use of chromatographic methods. The results indicate that somatostatin and gastrin are released into the gastric lumen in preterm infants and that sucking of a pacifier, in connection with bolus feeding, stimulates the gastric motor functions and facilitates the digestion process, probably via activation of vagal mechanisms. PMID- 2899622 TI - Role of type 1 somatic pili (fimbriae) in mucosal attachment of the enteroadherent Escherichia coli, strain RDEC-1, in rabbits. AB - We have previously shown that attachment of the rabbit enteroadherent Escherichia coli, strain RDEC-1, to ileal brush borders in vitro is mediated by both mannose resistant, AF/R1 pili and mannose-sensitive, type 1 pili. Because the role of type 1, somatic pili as adhesins that mediate bacterial enteroadherence in vivo remains controversial, we examined adherence of RDEC-1 expressing either type 1 pili or AF/R1 pili to rabbit ileum in ligated loops and after oral infection of rabbits. A rabbit fecal commensal E. coli, 640, which also expressed type 1 pili was used as a control. After oral infection of rabbits we evaluated: (a) diarrhea, (b) fecal shedding of organisms, (c) luminal colonization of jejunum and ileum, and (d) mucosal adherence of bacteria to jejunum, ileum, and colon. RDEC-1 expressing either type 1 or AF/R1 pili adhered to enterocytes both in ileal ligated loops and in the distal ileum, cecum, and proximal colon of infected rabbits. In contrast, enteroadherence of 640 was not observed. Diarrhea developed in rabbits challenged with either type 1 or AF/R1 piliated RDEC-1, but not in rabbits fed 640. Seven days after infection of rabbits with RDEC-1 bearing type 1 pili, luminal colonization of jejunum (4.22 +/- 0.55 CFU/g, X +/- SE) and ileum (6.34 +/- 0.55) was the same as after infection with AF/R1 piliated RDEC-1 (jejunum 4.47 +/- 0.20, ileum 5.81 +/- 0.70) and significantly greater than luminal colonization by type 1 piliated 640 (jejunum less than 2.22 +/- 0.14, ileum less than 2.06 +/- 0.15).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899623 TI - Characterization of sodium carboxymethylcellulose-gelatin complex coacervation by chemical analysis of the coacervate and equilibrium fluid phases. AB - The complex coacervation of sodium carboxymethylcellulose (SCMC) and gelatin has been characterized by chemical analyses of the coacervate and equilibrium fluid phases. The phenol-sulphuric acid (for SCMC) and Lowry (for gelatin) assays were used. Chemically analysed coacervate yield was used to predict optimum coacervation conditions, which occurred at a SCMC-gelatin mixing ratio of 3:7 at pH 3.5. The effects of pH, colloid mixing ratio and total colloid concentration on coacervate yield and composition were studied. The colloid mixing ratio, at which the peak coacervate yields occurred varied with coacervation pH. Increase in the total colloid concentration suppressed coacervation, resulting in a coacervate of higher water content. A similar coacervation mechanism was seen for two viscosity grades SCMC. However, because of the different degree of substitution of these two grades the SCMC-gelatin coacervates had different SCMC contents. PMID- 2899624 TI - The effects of inclusions and conditions of storage on the mechanical properties of maize starch and methylcellulose films. AB - Films of methylcellulose and gelatinized maize starch were tested in tension, with and without 0.01-10% of additive in the film. The effects of these inclusions on the physical properties of the films have been found to be statistically significant in almost every case. The films, with and without inclusions, have also been conditioned at four different relative humidities and the behaviour of these films has also been considered. In general films were weakened by the presence of additives particularly at higher concentrations. The properties of methylcellulose films were changed most at specific concentrations of the inclusions, this effect was not found with maize starch films. Plasticization of maize starch films was not achieved. PMID- 2899625 TI - Stereospecific absorption and degradation of cephalexin. AB - Stereospecific absorption and degradation of two stereoisomers about the alpha amino group at the 7-position of cephalexin (CEX) have been investigated in the rat intestine. The L-isomer (L-CEX) was not found to be present either in serum or urine after oral administration, but the D-isomer (D-CEX) was well absorbed. In contrast to the saturable uptake of D-CEX (Kt = 10.54 +/- 1.73 mM, pH = 6.0) by the in-vitro everted intestinal sac, no appreciable uptake of L-CEX was observed. However, L-CEX competitively inhibited the uptake of D-CEX by the in vitro everted intestine and the inhibitory constant (Ki) of L-CEX was determined to be 0.67 +/- 0.09 mM. L-CEX was rapidly degraded in-vitro in the intestinal tissue homogenate, serum and urine, while there was no appreciable degradation of D-CEX. Analysis of the major metabolite of L-CEX by high-performance liquid chromatography identified it as 7-aminodeacetoxycephalosporanic acid (7-ADCA). Furthermore, 7-ADCA was detected in serum after oral administration of L-CEX, indicating significant absorption of L-CEX as well as D-CEX. The results obtained suggest that both L- and D-CEX can be absorbed through the intestinal brush border membrane via the same mechanism, most likely through the dipeptide transport system, and that the affinity of L-CEX to the carrier system is higher than that of D-CEX.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899626 TI - Toxicity of solubilized and colloidal amphotericin B formulations to human erythrocytes. AB - The toxicity of a number of solubilized or colloidal amphotericin B formulations to human erythrocytes has been studied in-vitro. All the solubilized formulations studied, using poloxamer F127 or L92, or sodium deoxycholate as solubilizing agents, showed similar toxicity, erythrocyte lysis being greater than 90% for amphotericin B concentrations between 4 to 8 micrograms mL-1. Emulsion formulations stabilized by poloxamers showed reduced toxicity, while those stabilized by egg lecithin showed less than 5% erythrocyte lysis up to an amphotericin B concentration of 200 micrograms mL-1. The mechanisms of the differential toxicity is considered to be due to the differences in the equilibrium concentration of free amphotericin B in the aqueous phase. PMID- 2899627 TI - Rate-controlled absorption enhancement of rectally administered cefazolin in rats by a glyceride mixture (MGK). AB - The enhancing effect of the medium chain glyceride preparation MGK on the rectal absorption of the cephalosporin antibiotic cefazolin sodium was evaluated in relation to the rate of delivery. Cefazolin sodium proved to be absorbed to a small extent (15 to 27%) after rectal administration without MGK. Bolus administration with MGK enhanced rate and extent of cefazolin sodium absorption, resulting in a bioavailability of 57 +/- 26%. Linear infusion of 3 mg cefazolin sodium with MGK in 32 min produced complete absorption of the antibiotic (102 +/- 7%), but absorption occurred slower in comparison with bolus delivery. The rate of administration proved to be an important variable of the absorption enhancing effect of MGK. PMID- 2899628 TI - Glycogenolysis in the rat isolated perfused liver as a measure of chemically induced liver toxicity. AB - The relationship between chemically induced glycogenolysis and decreased thiol content in the rat isolated, perfused liver has been examined. Chemicals such as 2,4-dinitrophenol (DNP), diethyl maleate, alcohols and anti-inflammatory agents (except for sodium salicylate) accelerated glycogenolysis. Protein thiol loss correlated well with a marked increased rate of glucose release. Non-protein thiol loss, without significant loss of protein thiol, caused by a slight increase in the rate of glycogenolysis compared with controls. Since it has been reported that protein thiol loss rather than non-protein thiol loss is correlated to liver cell injury, a marked glucose release from the perfused liver may be a convenient measure of hepatic toxicity for a variety of chemicals. PMID- 2899630 TI - Tissue distribution and excretion of amodiaquine in the rat. AB - 14C-Labelled amodiaquine ([14C]AQ) has been administered to male Wistar rats by oral and intravenous routes (n = 6 for each route of administration). Excretion of total 14C-activity was predominantly in the faeces after both oral and intravenous administration. After oral administration 86 +/- 8.3% (mean +/- s.d.) of the 14C administered had been excreted (77 +/- 9% in the faeces, 7 +/- 1% in the urine and 2 +/- 2% in cage washings) over 72 h. Of the 14C administered, 4 +/ 1% was recovered from the tissues, and this was widely distributed, with the main organs of accumulation being kidney, liver, red bone marrow and spleen. After intravenous administration, 102.6 +/- 9.7% of the 14C had been excreted (90.9 +/- 9.6% in faeces, 10.9 +/- 0.8% in urine and 0.5 +/- 0.2% in cage washings) over 72 h. High-performance liquid chromatographic analysis of urine and faeces samples following oral administration of 14C-AQ (8.6 mg kg-1; base) revealed recoveries of 210 +/- 70 micrograms amodiaquine (AQ) and 123 +/- 32 micrograms desethylamodiaquine (AQm) in the faeces, and 2.4 +/- 0.5 micrograms AQ and 18.5 +/- 4.1 micrograms AQm in the urine. Female Wistar rats (n = 6) each received [14C]AQ orally and were killed at the following times: 0.5, 1, 3, 6, 24 and 48 h. Autoradiographs were prepared from each animal and these revealed significant amounts of radioactivity in the tissues at 48 h. This was accumulated maximally by liver and kidney. Radioactivity was detected in bone marrow at 48 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899631 TI - The effects of fructose 1,6-diphosphate, caffeine and dantrolene sodium on suxamethonium-induced contractures in denervated rat skeletal muscle. AB - Previously unidentified forms of suxamethonium-induced contractures have been investigated in chronically denervated rat extensor digitorum longus (EDL) muscle at 20 degrees C. Contractures were assigned to groups 1-6 on the basis of the peak tension (Tp1) during 0-10 min exposure to the drug (3.0 x 10(-5) M), (7.0 x 10(-6) M), and (3.5 x 10(-6) M) and the subsequent retention, increase, or decrease in tension (Tp2), during the further 10 min. It is proposed that four stages exist in the development of contractile changes at 1-7, 8-35, 36-70 and 70 130 days after denervation (DPD) and that contractility is lost at 147 days after denervation. Initial changes, although present in EDL muscles in group 1 at 2.0 DPD s.d. +/- 1 (n = 7) in response to the drug (3.0 x 10(-5) M), were more apparent in EDL muscles in group 2 which were identified at 5.5 DPD s.d. +/- 1.6 (n = 7) by an excessive contracture response (Tp2) to the drug (3.0 x 10(-5) M), 18.3 mN s.d. +/- 10.6. At 5.0 DPD s.d. +/- 2.7 (n = 5) contracture tension (Tp2) was commensurate with membrane depolarization, 13.1 mN/33.1 mV, but residual tension increased to 23.3 mN during the Krebs wash (80 min) whilst membrane depolarization decreased to 9.2 mV. Also, at 4.3 DPD s.d. +/- 2.3 (n = 5) tension (Tp2) increased significantly (P less than or equal to 0.05) in the presence of caffeine (4.1 x 10(-3) M).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899629 TI - The distribution of doxorubicin in mice following administration in niosomes. AB - Large multilamellar non-ionic surfactant vesicles (niosomes) with diameters of around 800-900 nm prepared from a C16 triglyceryl ether with and without cholesterol and containing doxorubicin (Adriamycin) were administered to S180 tumour-bearing NMRI mice by bolus injection. Although in-vitro drug release from cholesterol-containing niosomes is delayed, in-vivo there was little difference between the two preparations when plasma levels were compared. As previously observed, half-lives of the drug were prolonged compared with free solution profiles. Liver uptake was not significantly affected by niosome encapsulation of doxorubicin. There is minor accumulation of drug in the lung, perhaps because of aggregation of the vesicles and their physical entrapment. Tumour levels of drug were higher following administration of cholesterol-containing niosomes and this was reflected in the more effective reduction in tumour growth. Metabolism of doxorubicin is altered by niosomal administration, but more studies are required before the significance of the metabolic data can be assessed. PMID- 2899632 TI - Particulate contamination in solutions of antibiotics packed as dry powders in vials. AB - The particulate contamination in 12 formulations of antibiotic solutions in vials packed as dry powders from five South African sources has been analysed quantitatively using a HIAC PC 320 light blockage particle analyser linked to a CMB 60 sensor. Results showed that the level of particulate contamination fell well within the limits set by the USP XXIst Edition for Small Volume Parenterals although four formulations contained some particles greater than or equal to 50 micron. There was no apparent difference between the quality of the same antibiotics from different sources or between vials of the same antibiotics packed in different strengths. PMID- 2899633 TI - The effect of moisture on the cohesive properties of microcrystalline celluloses. AB - A comparative evaluation of two microcrystalline celluloses, Avicel PH101 and Emcocel, revealed some differences in their cohesive properties at different moisture contents. A new method of sandwich rheometry was used to evaluate the cohesive properties of different powder masses. The force required to cause shear failure of a rough-surfaced blade in a powder bed was recorded. Avicel PH101 was found to be more cohesive than Emococel at moisture contents less than 30 wt%, whereas at higher moisture contents the cohesive behaviour was comparable. PMID- 2899634 TI - Presynaptic changes promoted by alloxan diabetes in the cat isolated heart. AB - Adrenergic presynaptic functions were evaluated in the cat isolated perfused heart preparation. The sympathetic nerve endings were labelled with [3H]noradrenaline ([3H]NA) and the effect of electric neural stimulation was determined in the presence of drugs which inhibit neuronal or extraneuronal uptake, or which antagonize alpha-adrenoceptors. [3H]NA overflow was measured in control and diabetic cats and was significantly increased by electric neural stimulation on both conditions. Perfusion with 0.1 microM phentolamine increased transmitter overflow in control hearts but failed to do so on organs obtained from alloxan-treated cats. The data provide evidence that in alloxan diabetic cats there is an abnormality of the adrenergic synapse. PMID- 2899635 TI - Differences in the development of tolerance to two anticonvulsant benzodiazepines in the amygdaloid kindled rat. AB - The effects of chronic treatment with two benzodiazepines were studied on kindled amygdaloid seizures in rats. Clobazam (4 mg kg-1), clonazepam (0.3 mg kg-1) or vehicle (1 mL kg-1) was administered, by intraperitoneal injection, to fully kindled rats twice daily for nineteen days. Each rat was electrically stimulated 30 min after the morning dose on alternate days of treatment. Tolerance developed rapidly to the anticonvulsant effects of clobazam after only three days of treatment, following which only a small residual protection was maintained. Tolerance to clonazepam developed gradually over the course of the experiment, although this effect was relatively minor. PMID- 2899637 TI - The therapeutic effect of sodium stibogluconate in BALB/c mice infected with Leishmania donovani is organ-dependent. AB - A study of the antileishmanial efficacy of sodium stibogluconate was carried out in BALB/c mice. The drug was administered to Leishmania donovani-infected animals on days 7 and 8 post-infection in one of three forms; free (40-50 mg Sbv Kg-1), liposomal, or niosomal (6.4-8.0 mg Sbv Kg-1) drug. On day 14 post-infection counts of the number of parasites present in the liver, spleen and bone marrow of treated and control animals showed that although all three drug preparations significantly reduced parasite numbers in the liver (approximately equal to 99% suppression) they had little effect on those residing in the spleen or bone marrow. The carrier forms of the drug were therefore significantly more effective than free drug in reducing liver parasite burdens. Increasing the concentration and the number of doses of free drug (maximum of 500 mg Sbv Kg-1), and reducing the size of the vesicles used to deliver the drug had a minimal effect on parasite numbers in the spleen and bone marrow. It is proposed that because of the resistance of spleen and bone marrow parasites to drug therapy, the BALB/c mouse infected with L. donovani provides an excellent model system for the study of drug delivery to these deeper tissue sites. PMID- 2899636 TI - Intracerebroventricularly administered bradykinin augments carrageenan-induced paw oedema in rats. AB - Intracerebroventricular (i.c.v.) administered bradykinin (2.5 and 5.0 micrograms/rat) was found to augment carrageenan-induced acute paw oedema throughout the 4 h post-carrageenan observation period. The effect was statistically significant with the higher dose. The pro-inflammatory effect of i.c.v. bradykinin was antagonized following pretreatment with hemicholinium and atropine ethoiodide administered i.c.v., drugs that reduce central cholinergic activity. Similarly, central administration of drugs that inhibit the synthesis of eicosanoids, hydrocortisone, diclofenac and paracetamol, also attenuated the pro-inflammatory effect of bradykinin. The findings indicate that the inflammation-promoting effect of centrally administered bradykinin involves the central prostaglandin and cholinergic neurotransmitter systems. PMID- 2899638 TI - Prolonged apparent half-life of delta 1-tetrahydrocannabinol in plasma of chronic marijuana users. AB - The aim of this study was to characterize the elimination half-life of delta 1 tetrahydrocannabinol in blood plasma in chronic marijuana users. The subjects smoked four cigarettes during a two day period, each cigarette containing 15 mg deuterium-labelled delta 1-tetrahydrocannabinol. The plasma concentrations of deuterium-labelled tetrahydrocannabinol were measured for 13 days using gas chromatography-mass spectrometry equipped with selected ion monitoring. The elimination half-life for delta 1-tetrahydrocannabinol in blood plasma was calculated to be 4.1 +/- 1.1 days (range 2.9-5.0 days) from the two week plasma level curves. Albeit the present results are based upon a small sample, an elimination half-life of delta 1-tetrahydrocannabinol in blood plasma of about 4 days is more in line with apparent half-life excretion of delta 1 tetrahydrocannabinol metabolites in the urine of chronic marijuana smokers. PMID- 2899639 TI - The effect of capsule size and density on transit through the proximal colon. AB - Colonic transit of radiolabelled capsules has been monitored in 18 healthy subjects using gamma scintigraphy. The capsules ranged in volume from 0.3-1.8 cm3 and in density from 0.7-1.5 gcm-3. The capsules were administered after an overnight fast and entered the colon, on average, 5 h after dosing. Transit rates through the proximal colon were independent of capsule density. Any effect due to capsule volume was small when compared with intersubject variations in transit rates. Within 10 h of entering the colon 80% of the units had reached the splenic flexure. These findings have implications in the design of non-disintegrating, sustained release dosage forms. PMID- 2899640 TI - The effects of the selective kappa-opioid agonist MR 2034 on the guinea-pig ileum. AB - The effects of the selective kappa-opioid agonist MR 2034 on the guinea-pig ileum were compared with those produced by the mu-agonist morphine. MR 2034 induced acute tolerance and inhibited electrically evoked contractions to the same extent as morphine. The slope of the concentration-effect curve to MR 2034 was not significantly different from that of morphine. However, MR 2034 and morphine may act at their respective receptors since naloxone was 6.57 times more effective at inhibiting responses to morphine than MR 2034. MR 2034, like morphine, induced acute dependence as revealed by naloxone-induced contractions of tissues that had been incubated with MR 2034 for 5 h. The functional properties of kappa-opoid receptors are the same as mu-receptors in the guinea-pig ileum. PMID- 2899641 TI - "The influence of conformational factors on the metabolic conjugation of aryloxyacetates"--a comment. PMID- 2899642 TI - Freeze-fracture study of the trophozoite and the cyst of Entamoeba histolytica. AB - The fine structure of the trophozoite and cyst of Entamoeba histolytica from the stool of a patient was compared using the freeze-fracture method. The intramembranous particles (IMP's) were heterogeneously distributed on the plasma membrane of the trophozoite and their density was 1139 +/- 105/micron 2 on the P face. Particle-rich depressions and linear particle arrays, reported by other investigators on cultured trophozoites, were also observed on the P face while on the E face such special particle arrangement was not recognized. Particle-free, small protrusions were frequently observed on the P face of the trophozoite membrane. The existence of these protrusions is a new finding. In the cyst, the IMP's were also distributed heterogeneously on both the P and E faces of the plasma membrane. The density of the IMP's, however, was much lower than in the trophozoite: 6 +/- 2/micron 2 on the P face and averaging less than 1/micron 2 on the E face. In freeze-fracture images, the plasma membrane of the cyst showed a variety of configurations from smooth to uneven or ridged surfaces. These morphological alterations of the plasma membrane may be attributed to the aging of the cyst. The thick wall of the cyst had a filamentous tri- or tetra-lamellar structure. The cytoplasm of the cyst was similar in structure to that of the trophozoite and the diameter of the nuclear pores was equal in both trophozoites and cysts. PMID- 2899643 TI - Growth hormone and its modulation. AB - Our knowledge of the mechanisms involved in the regulation of somatotroph cell growth is scanty and much work is still needed to elucidate the role of different growth factors and the mechanisms involved in oncogene activation in both normal and tumour cell growth. However, there are several recent, important clinical ramifications from our improved understanding of GH neuroregulation. The use of long-acting SS analogues is valuable in the treatment of acromegaly, probably in acute variceal haemorrhage and it also produces symptomatic improvement in patients with vipomas and glucagonomas. GHRH may be of value in the treatment of short stature due to hypothalamic GHRH deficiency but further definitive studies are now required to provide convincing evidence that this line of treatment is of greater benefit than the use of synthetic recombinant human GH. Inhibition of GH release may be of value in prevention of both acute and chronic complications of insulin-dependent diabetes mellitus. The use of cholinergic muscarinic receptor blockade in this context may be particularly useful because of a probably sparing of the counter-regulatory GH response to hypoglycaemia. In view of the relative ease with which nocturnal GH secretion can be abolished, we think it reasonable to consider the possible existence of a permissive or mediating role of GH in other disease states, either directly or by maintaining production of either local tissue or circulating growth factors or both. PMID- 2899644 TI - Role of the fetal pituitary in cryptorchidism induced by exogenous maternal oestrogen during pregnancy in mice. AB - A single subcutaneous injection of 5 or 1 mg oestradiol given to pregnant female mice on Day 14 of pregnancy resulted in all male offspring being cryptorchid. Pituitary LH content, testicular weights and structure, seminal vesicle weights and the structure of the reproductive tract as a whole were monitored on the day of birth and at 2, 4, 8 and 14 weeks of age. Apart from an initial significant reduction in pituitary LH at the time of birth, no other marked differences were seen between control and treated animals except that all oestrogen-treated males lacked a gubernaculum and the testes were freely mobile within the abdomen. Hypogonadal (hpg) male mice lacking GnRH are cryptorchid but have a normal gubernaculum and their testes develop and descend normally if treated with gonadotrophins. When the mothers of hpg mice were treated with oestradiol the male offspring lacked a gubernaculum. These results indicate that perturbations of the fetal hypothalamic/pituitary axis play no significant part in oestrogen induced cryptorchidism in mice. PMID- 2899645 TI - Sulfasalazine treatment and lymphocyte function in patients with rheumatoid arthritis. AB - Sulfasalazine is now an established 2nd line agent in the treatment of rheumatoid arthritis (RA) but its mode of action is unknown. Two separate studies have investigated the possibility that it works in RA by influencing lymphocyte function. After 12 weeks of treatment with sulfasalazine, elevated levels of circulating activated lymphocytes and abnormal ex vivo mitogen response to concanavalin A (Con-A) in 11 patients with RA reverted to normal. An in vitro study investigated the effect of sulfasalazine and its metabolites on mitogen response by healthy and RA peripheral blood mononuclear cells (PBMC). Sulfapyridine (SP) and 5-hydroxy SP suppressed the response of RA PBMC to Con-A. Sulfasalazine, SP and N-acetyl SP suppressed the response of healthy PBMC to pokeweed mitogen. 5-aminosalicylic acid also affected mitogen response and cell viability, which may be relevant to actions of this metabolite within the gut. PMID- 2899646 TI - In vitro immunomodulatory effects of sulfasalazine and its metabolites. AB - We assessed the in vitro effects of sulfasalazine and its 2 main metabolites, sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA) on functional aspects of peripheral blood lymphocytes (PBM) of normal controls and patients with rheumatoid arthritis (RA). Sulfasalazine, but not its 2 main metabolites, inhibited mitogen induced proliferative responses of PMB at high drug concentrations (100 micrograms/ml). Similar results were obtained with purified B lymphocytes. Sulfasalazine depressed, in a dose dependent manner, pokeweed mitogen induced Ig synthesis by PBM of normals and patients with RA. Moreover, synthesis of IgM rheumatoid factor was depressed to a greater degree than total IgM at low sulfasalazine concentrations (10-25 micrograms/ml). Both SP and 5-ASA were not inhibitory at the concentrations tested. Experiments with purified lymphocyte subpopulations indicated that sulfasalazine exerted its major inhibitory activity on the B lymphocyte. These studies indicate that sulfasalazine, but not its 2 main metabolites, has immunomodulatory characteristics which may be related to its therapeutic activity in RA. PMID- 2899647 TI - Dopamine autoreceptor agonists as potential antipsychotics. 1. (Aminoalkoxy)anilines. AB - The synthesis and pharmacological properties of a novel type of [(arylpiperazinyl)alkoxy]anilines with dopaminergic properties are described. One of these compounds, 3-[3-(4-phenyl-1-piperazinyl)propoxy]benzenamine (4c), has been identified as a selective dopamine (DA) autoreceptor agonist in tests that include [3H]haloperidol binding, inhibition of striatal DA synthesis, inhibition of DA neuronal firing, inhibition of spontaneous locomotor activity, and reversal of reserpine-induced depression in rats. In addition, 4c possesses good oral activity in the Sidman conditioned avoidance test in squirrel monkeys, which is indicative of antipsychotic activity. In a primate model, 4c was found to lack the liability for extrapyramidal side effects usually associated with antipsychotic drugs. PMID- 2899648 TI - Differentiation of phase I and variant strains of Bordetella pertussis on Congo red media. AB - The addition of Congo red, Trypan blue or haemin to the growth medium allowed the differentiation of phase-I and variant strains of Bordetella pertussis. Phase-I strains produced red (CR+), blue or dark brown colonies on a modified cyclodextrin solid medium containing Congo red, Trypan blue or haemin, respectively, whereas variant (Vir- and phase IV) strains grew as pale (CR-) colonies. Spontaneous CR- variants were isolated and characterised and had a phenotype like that of Vir- or phenotypically modulated, C-mode strains in that they did not produce the haemolysin, haemagglutinin(s), histamine-sensitising factor (pertussis toxin), heat-labile toxin and two major envelope polypeptides associated with phase-I strains. Two such variants had reduced virulence for mice. CR+ strains, when grown on a high nicotinic acid medium to induce modulation, gave CR- colonies. Thus the CR+ phenotype is a characteristic of phase-I B. pertussis and its expression appears to be controlled in a manner similar to that of other phase I-related factors. CR- variants of B. parapertussis and B. bronchiseptica were also deficient in these factors. Four isolates of B. avium were CR-. PMID- 2899649 TI - Complications of Crotalidae antivenin therapy. AB - Polyvalent antivenin is the mainstay of treatment of serious snake envenomation. Its use, however, has been challenged as being unnecessary in minor envenomations and potentially hazardous due to allergic complications. Our institution routinely uses antivenin, and this report focuses on the allergic complications of this therapy. Forty patients with Crotalidae snake bites were evaluated and treated over a 7-year period. Twenty-six patients received a total of 507 vials of antivenin, the dose correlating with the clinical severity of envenomation. All patients were skin tested. Immediate hypersensitivity reactions occurred in six patients (23%). Cutaneous manifestations alone occurred in three of these patients, while systemic anaphylaxis occurred in three. Twenty patients were available for followup, and ten (50%) developed serum sickness. Skin testing was not reliable in predicting the development of immediate (anaphylaxis) or delayed (serum sickness) hypersensitivity reactions. Treatment of antivenin allergic reactions was uniformly effective, with no mortality, minimal morbidity, and no chronic sequelae. PMID- 2899650 TI - Bethanechol supersensitivity test, rhabdosphincter electromyography and bulbocavernosus reflex latency in the diagnosis of neuropathic detrusor areflexia. AB - A total of 57 patients with neuropathic or nonneuropathic detrusor areflexia was studied with the bethanechol supersensitivity test, electromyography of the urethral rhabdosphincter and bulbocavernosus reflex latency. The sensitivity of these tests in detecting neuropathic areflexia was 90, 87.5 and 78.1 per cent, respectively, and the specificity was 95.6, 76 and 80 per cent, respectively. When all 3 tests were performed together the combined accuracy approached 100 per cent. These combined tests are useful in the diagnosis of patients with equivocal bladder neuropathic conditions and in those with subtle neurological lesions. PMID- 2899651 TI - [A chronic ATL patient showing epidermal eruptions with a leaking of ATL cells from hair pouches]. PMID- 2899652 TI - [Epididymal abnormalities associated with cryptorchidism]. PMID- 2899653 TI - [A case of periarteritis nodosa with bronchial asthma simulating a tumor of the stomach]. PMID- 2899654 TI - Adult T-cell leukemia/lymphoma: a retroviral malignancy endemic in South Carolina. PMID- 2899655 TI - Inverse correlation between dexamethasone 21-mesylate agonist activity and sensitivity to dexamethasone for induction of tyrosine aminotransferase in rat hepatoma cells. AB - Previous results demonstrated that both the level of induction of the liver specific enzyme tyrosine aminotransferase (TAT) by the irreversible antiglucocorticoid dexamethasone 21-mesylate (Dex-Mes) and the concentration of the reversible glucocorticoid dexamethasone (Dex) required for 50% of maximal TAT induction (i.e. EC50) were different in HTC and Fu5-5 rat hepatoma culture cells. In the present study, a retrospective analysis of these two parameters over an 8 yr period indicates that the absolute values of both parameters varied within each cell line over time in a reversible manner. The variation of both parameters appears to be causally related since a linear, reciprocal relationship exists between the amount of Dex-Mes agonist activity and log10 (Dex EC50) in both cell lines (correlation coefficient is -0.896 for n = 46). This relationship was independent of changes in basal TAT level, culture medium, and serum lot. Results with cloned HTC cells indicate that these temporal variations are not due to fluctuations in the relative abundance of two cell populations displaying either high or low amounts of agonist activity with Dex-Mes. While these analyses relied on the detection of enzyme levels, the amount of TAT mRNA is shown to parallel the enzyme levels. Thus the variation in parameters of TAT induction by Dex and by Dex-Mes appears to be modulated at a pre-translational step. Such variations have not previously been observed for the control of specific gene transcripts by other steroid hormones and may be related to the known differences in agonist activity seen for most antisteroids in various systems. PMID- 2899656 TI - Young domestic pigs for the cardiovascular assessment of inotropic drugs. Comparison with dogs. AB - A comparison is made of cardiovascular response to cardiotonic drugs in young domestic pigs and dogs, and the use of pigs as an alternative to dogs in cardiovascular investigations is described. PMID- 2899657 TI - [Neurofibromatosis, glioma of the optic nerve and multiple endocrine tumors. Presentation of a case]. PMID- 2899658 TI - [Management of insulinoma with the somatostatin analog SMS 201-995]. PMID- 2899659 TI - Potentiation of the gastric antisecretory activity of histamine H2-receptor antagonists by clebopride. AB - The substituted benzamide, clebopride, at doses (0.03-3 mg kg-1 i.p.) that were without effect per se on the secretion of gastric acid in pylorus ligated (Shay) rats, potentiated the antisecretory effects of the histamine H2 receptor antagonists cimetidine and ranitidine in this model but not those of the muscarine receptor antagonist pirenzepine nor those of the proton pump inhibitor omeprazole. By contrast, clebopride was without influence on the inhibitory effects of cimetidine on pentagastrin-induced secretion in perfused stomach (Ghosh and Schild) preparations in anaesthetized rats. The significance of these findings is discussed in relation to the previously described potentiating effects of clebopride on the anti-ulcer activity of cimetidine in various experimental models, and the potential beneficial effects of such combined therapy in the clinic. PMID- 2899660 TI - Double-masked trial of azathioprine in multiple sclerosis. British and Dutch Multiple Sclerosis Azathioprine Trial Group. AB - 354 patients with multiple sclerosis were randomised to receive either azathioprine 2.5 mg/kg daily or placebo in a double-masked trial. During follow up of at least 3 years only small differences emerged between the groups. After 3 years the mean deterioration in Kurtzke disability score was 0.62 in the azathioprine group and 0.80 in the placebo group, a difference of 0.18 (95% confidence intervals [CI] -0.15 to +0.52) and in the ambulation index it was 0.84 and 1.25, respectively, difference 0.41 (95% CI 0.03 to 0.80). After 3 years there had been slightly fewer relapses in the azathioprine group (average 2.2) than in the placebo group (average 2.5) but the difference of 0.3 (95% CI -0.2 to +0.9) was not significant. Although the results favour a small beneficial effect from azathioprine the benefit is so small that the use of azathioprine cannot be generally recommended for most patients with multiple sclerosis. Analysis of subgroups (by sex, age, severity, rate of progression, HLA status, relapsing or progressive course) has not revealed any that have shown clear clinical benefit. PMID- 2899661 TI - Lytic anti-endothelial cell antibodies in haemolytic-uraemic syndrome. AB - Sera from 13 of 14 children with acute haemolytic uraemic syndrome (HUS) contained complement-fixing IgG and IgM antibodies that lysed cultured human umbilical vein endothelial cells. In 3 of 3 sera tested, no lysis of dermal fibroblasts was observed. The endothelial cell antigen was lost after treatment of the cells with gamma interferon. In contrast, only 3 of 5 adult patients with acute, non-relapsing, thrombotic thrombocytopenic purpura (TTP) had lytic anti endothelial antibodies and only 1 of these recognised an antigen lost upon gamma interferon treatment. None of 32 control sera contained lytic anti-endothelial cell antibodies. These data suggest that HUS involves a disorder of immunoregulation and that a unique class of anti-endothelial cell antibodies is produced that may take part in the pathogenesis of vascular injury in HUS. PMID- 2899662 TI - Virus safety of solvent/detergent-treated antihaemophilic factor concentrate. AB - The safety of an antihaemophilic factor concentrate treated with the organic solvent tri-(n-butyl)phosphate and sodium cholate (factor VIII-SD) was assessed for transmission of non-A, non-B (NANB) hepatitis and human immunodeficiency virus (HIV). Patients enrolled in the study had no previous exposure to blood products made from plasma pools, although 5 had received small quantities of single-donor products. All but 1 had normal alanine aminotransferase (ALT) levels, none had markers of HIV infection, and all had been vaccinated against hepatitis B. After treatment with factor VIII-SD, serum ALT levels and HIV antibody were monitored for up to 1 year. 20 patients received 625 to greater than 40,000 U (total 163,000 U, median dose 3900 U), and 17 of these were followed up for at least 6 months: transmission of either NANB hepatitis or HIV was not observed. PMID- 2899664 TI - Heart-lung transplantation for cystic fibrosis. AB - 13 patients with severe lung disease and cor pulmonale from cystic fibrosis were accepted for heart-lung transplantation (HLT). 6 have had the operation, of whom 5 are well, with normal lung function, 3-29 months after operation. 1 patient died from adult respiratory distress syndrome after reoperation to control persistent chest-wall bleeding: at necropsy, this patient proved to have cirrhosis. Respiratory tract infections and acute lung rejection after HLT for cystic fibrosis were no more common than in other HLT patients. Of the 7 patients for whom suitable donor organs were not found, 3 died within 3 months of assessment. Initial severity of disease had been similar to that in the transplant group. The cost of assessment, operation, and 1 year's treatment after HLT is similar to that of medical treatment for such patients. PMID- 2899665 TI - The shock of the new. PMID- 2899663 TI - Randomised double-blind placebo-controlled trial of feverfew in migraine prevention. AB - The use of feverfew (Tanacetum parthenium) for migraine prophylaxis was assessed in a randomised, double-blind, placebo-controlled crossover study. After a one month single-blind placebo run-in, 72 volunteers were randomly allocated to receive either one capsule of dried feverfew leaves a day or matching placebo for four months and then transferred to the other treatment limb for a further four months. Frequency and severity of attacks were determined from diary cards which were issued every two months; efficacy of each treatment was also assessed by visual analogue scores. 60 patients completed the study and full information was available in 59. Treatment with feverfew was associated with a reduction in the mean number and severity of attacks in each two-month period, and in the degree of vomiting; duration of individual attacks was unaltered. Visual analogue scores also indicated a significant improvement with feverfew. There were no serious side-effects. PMID- 2899667 TI - The MRC's muffler. PMID- 2899666 TI - HIV testing in the workplace. PMID- 2899668 TI - Seronegative (reactive) arthropathy: precipitating factors. PMID- 2899669 TI - Physical therapy in spastic diplegia. PMID- 2899671 TI - Physicians and the bomb. PMID- 2899670 TI - Nebulisers and paradoxical bronchoconstriction. PMID- 2899672 TI - Looking back, seeing ahead. PMID- 2899673 TI - Survival of the smallest. Time trends and determinants of mortality in a very preterm population during the 1980s. AB - In a regionally representative preterm birth cohort, the fetal to first year survival of very preterm infants born at 32 weeks' gestation or less increased from 54% to 66% between 1978 and 1986. This improvement was due to a fall in numbers of stillbirths while neonatal mortality either declined or remained the same. Only among extremely immature preterm babies born at 26 weeks or less was improvement in fetal survival counteracted by an increase in neonatal mortality. Fewer than 5% of complete fetal to first year deaths occurred postneonatally. After the age of 26 gestational weeks, intrauterine growth retardation was a major unfavourable factor, associated with a 3-fold increase in neonatal mortality. PMID- 2899674 TI - Amblyopia--factors influencing age of presentation. AB - In the 47 months from September, 1981, 1531 new cases of amblyopia were identified in the ophthalmic clinics of Leicestershire. Amblyopia was due to strabismus in 689 (45%), combined strabismus and anisometropia in 540 (35%), anisometropia alone in 252 (17%), and form deprivation in 50 (3%). The median age at presentation for strabismic amblyopia (3.64 years) was significantly lower than for combined strabismus and anisometropia (4.68 years) and anisometropia (6.27 years). Boys presented later than girls, as did Asians compared with Caucasians. Only 38 (15%) of children with a visual defect without strabismus (anisometropia) were identified before the age of 5 years. The major reason for this late identification is the lack of a reliable single test for preschool vision assessment. PMID- 2899675 TI - Window of opportunity. PMID- 2899676 TI - Continuous intrapartum measurement of fetal oxygen saturation. PMID- 2899677 TI - Lithotripsy of inaccessible salivary duct stone. PMID- 2899678 TI - Clinical significance of penicillamine antibodies. PMID- 2899679 TI - Missed diagnosis of infective endocarditis. PMID- 2899681 TI - Polycystic ovarian syndrome treated by laser through the laparoscope. PMID- 2899680 TI - Low-dose aspirin improves fetal weight in umbilical placental insufficiency. PMID- 2899682 TI - Assessing the hypothalamo-pituitary-adrenal axis. PMID- 2899683 TI - Dissolution of calcified gallbladder stones by treatment with methyl-hexyl ether and urea-EDTA. PMID- 2899684 TI - Intranasal glucagon for hypoglycaemia. PMID- 2899685 TI - Natural history of localised prostatic cancer managed by conservative therapy alone. PMID- 2899686 TI - In-vitro production of human platelets. PMID- 2899687 TI - Ciprofloxacin vs ceftriaxone for eradication of meningococcal carriage. PMID- 2899688 TI - Differences in HLA types in children with insulin-dependent diabetes diagnosed in 1960s, 1970s, and 1980s. PMID- 2899689 TI - Life-threatening psoriasis relapse on withdrawal of cyclosporin. PMID- 2899690 TI - Anaemia and aluminium chelation therapy in dialysis patients. PMID- 2899691 TI - Colloids, anaphylaxis, and the heart. PMID- 2899692 TI - Cryptococcosis and AIDS. PMID- 2899693 TI - HIV-2-associated AIDS in the 1970s. PMID- 2899694 TI - HIV antibody on paper-dried sera. PMID- 2899695 TI - Autoimmunity in stiff man syndrome. PMID- 2899696 TI - Ultrasound in diagnosis of infantile hypertrophic pyloric stenosis. PMID- 2899698 TI - Fetal "soap" addiction. PMID- 2899697 TI - Eat fat hen carefully? PMID- 2899700 TI - Drug promotion in the Third World. PMID- 2899699 TI - Pulmonary hypertension in gestational choriocarcinoma: a west London syndrome? PMID- 2899701 TI - Inactive ingredients in medicines. PMID- 2899702 TI - Litigation and private practice. PMID- 2899703 TI - Cover charge. PMID- 2899704 TI - Cytology services. PMID- 2899705 TI - Support for South African paediatricians. PMID- 2899706 TI - Gut bacterial metabolism. PMID- 2899707 TI - Is Alzheimer's disease distinct from normal ageing? PMID- 2899708 TI - Magnetic resonance imaging and magnetic eye implants. PMID- 2899709 TI - Toxic-shock syndrome after a minor surgical procedure. PMID- 2899711 TI - Lung-sound transmission and reliability of chest signs. PMID- 2899710 TI - Factor-VIII-related antigen and vasculitis. PMID- 2899712 TI - Cimetidine plus cisapride for reflux oesophagitis. PMID- 2899713 TI - Renal transplantation in sickle cell disease. PMID- 2899714 TI - Soft egg shells--carpal tunnel syndrome or sign of pollution? PMID- 2899715 TI - Failure of a deputising service. PMID- 2899717 TI - AIDS in the UK. PMID- 2899716 TI - Restricted discharge of mental patients. PMID- 2899718 TI - Randomised controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism. AB - The effect of intravenous recombinant human tissue-type plasminogen activator (rt PA) was compared with that of urokinase in 45 patients with angiographically documented pulmonary embolism (PE) in a randomised controlled trial. The two principal end-points were clot lysis at 2 h, as assessed by angiography, and pulmonary reperfusion at 24 h, as assessed by perfusion lung scanning. All patients received the full dose of rt-PA but urokinase infusions were terminated prematurely (on average after 18 h) in 9 patients because of allergy in 1 and uncontrollable bleeding in 8. By 2 h, 82% of rt-PA-treated patients showed clot lysis, compared with 48% of urokinase-treated patients (p = 0.008; 95% CI for the difference = 10-58%). Improvement in lung scan reperfusion at 24 h was identical in the two treatment groups. The reduction in fibrinogen did not differ significantly between the rt-PA and urokinase groups (45% vs 39% at 2 h and 34% vs 40% at 24 h). The results indicate that in the dose regimens employed, rt-PA acts more rapidly and is safer than urokinase in the treatment of acute PE. PMID- 2899719 TI - Long-term follow-up in a randomised controlled trial of recombinant alpha 2 interferon in Chinese patients with chronic hepatitis B infection. AB - 72 Chinese patients who had been positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) for more than six months with stable serum hepatitis B virus DNA were randomised to receive recombinant alpha 2-interferon at doses of 2.5, 5, or 10 X 10(6) U/m2 intramuscularly thrice weekly for 12-24 weeks, or no treatment. 6 (11%) of 54 treated and 1 (6%) of 18 control patients became HBeAg-negative at the end of therapy or after 24 weeks of follow-up. 9 (17%) of treated but none of the control patients became HBeAg-negative between completion of therapy and 12 months. Reactivation of HBV replication subsequently occurred in 7 (13%) of the treated patients and in 1 control. Thus, sustained clearance of HBeAg was achieved only in 8 (15%) of treated patients at 12 months. Between 12 and 24 months 3 (9%) of treated patients and 1 control became negative for HBeAg. None of the patients became HBsAg-negative. alpha 2-interferon in the dose regimen used has little long-term effect in the suppression of HBV replication in Chinese patients with chronic HBV infection. PMID- 2899720 TI - Cytomegalovirus infection and donor/recipient HLA antigens: interdependent co factors in pathogenesis of vanishing bile-duct syndrome after liver transplantation. AB - The contribution of cytomegalovirus (CMV) infection and its interrelation with HLA antigens in the development of chronic rejection (vanishing bile-duct syndrome--VBDS) was investigated in 101 patients surviving for at least 3 months after liver transplantation. A 1-2 antigen match for HLA DR antigens (30.9% vs 4.5% for zero DR match; p less than 0.002), a zero match for HLA A/B antigens (27.5% vs 10.9% for 1 or more A/B match; p less than 0.05), and active CMV infection (26.3% vs 4.4% for no CMV infection; p less than 0.005) were independently associated with an increased risk of VBDS. The coexistence of a 1-2 HLA DR match and CMV infection carried the highest relative risk (10.1) of VBDS; these two variables were probably interdependent since either alone was associated with a low relative risk (0.45 and 0.5). The association between VBDS and active CMV infection was not a consequence of alterations in immunosuppressive therapy. The findings would be consistent with precipitation of chronic rejection by CMV-induced HLA antigen expression in patients rendered susceptible by the donor/recipient HLA antigen match. PMID- 2899721 TI - Multicentre, cross-sectional study of ventricular arrhythmias in chronically haemodialysed patients. Gruppo Emodialisi e Patologie Cardiovasculari. AB - 127 patients on ambulatory in-hospital haemodialysis (HD) were randomly selected from 13 centres. The prevalence of ischaemic heart disease was 14%, 17% had left ventricular dysfunction, and 37% had left ventricular hypertrophy. Ventricular arrhythmias, assessed by continuous 48 h Holter monitoring, were present in 76% of patients. 29% had greater than or equal to 2 premature ventricular complexes (PVC)/h; 21% had Lown classes 4A or B; and 6% had greater than or equal to 3 consecutive beats of ventricular tachycardia. Risk factors for ventricular arrhythmias were age greater than or equal to 55 yr and left ventricular dysfunction, independent of age. The frequency of ventricular arrhythmias rose significantly during the third hour of HD, and this effect lasted for at least 5 h after dialysis, and was associated with age greater than or equal to 55 yr, left ventricular dysfunction, and the presence of ventricular arrhythmias before dialysis. Ventricular arrhythmias are present in a large proportion of patients with end-stage renal failure and HD has an arrhythmogenic effect. PMID- 2899722 TI - Diagnostic significance of octadeca-9,11-dienoic acid in cervical neoplasia. AB - The percentage molar ratio (%MR) of the 9,11 and 9,12 isomers of octadecadienoic acid was determined in cervical exfoliated cells from 148 subjects, of whom 27 had cytologically proven intraepithelial neoplasia and in cervical biopsy specimens from 43 subjects, of whom 24 had histologically diagnosed cervical intraepithelial neoplasia. The %MR in both cervical biopsy specimens and exfoliated cells did not significantly differ in subjects with or without cervical intraepithelial neoplasia. The measurement of the %MR of 9,11:9,12 octadecadienoic acid has no role in the detection of cervical intraepithelial neoplasia. PMID- 2899723 TI - Defective bile acid amidation: predicted features of a new inborn error of metabolism. AB - Biochemical and clinical features are predicted for an as yet unreported inborn error of metabolism, in which bile acids cannot be conjugated with glycine or taurine. Unconjugated cholic acid will be secreted into bile, be absorbed from the intestine, and become the predominant bile acid in bile and plasma. Other bile acids will be esterified with glucuronate and secreted into bile, but undergo little enterohepatic circulation. Cholestasis will not be present; the bile acid pool will be diminished and lipid absorption, especially that of fat soluble vitamins, will be impaired. A secretory diarrhoea may occur, caused by increased bile acid concentrations in the colon. Awareness of this possible syndrome should aid in its identification; oral administration of bile acids conjugated with glycine or taurine should correct the metabolic and clinical abnormalities. PMID- 2899724 TI - Radiation protection in the UK: an opportunity missed. PMID- 2899725 TI - Health care inequity in the USA. PMID- 2899726 TI - Lung function in children after neonatal meconium aspiration. PMID- 2899727 TI - Ubiquitin, protein degradation, and dynamic neuropathology. PMID- 2899728 TI - Escargots and eosinophilic meningitis. PMID- 2899729 TI - Role of infected food handler in hotel outbreak of Norwalk-like viral gastroenteritis: implications for control. AB - Investigation of an outbreak of viral (Norwalk-like) gastroenteritis amongst staff (40 cases), resident guests (over 70 cases), and persons attending functions (54 cases) at one hotel over 8 days suggested that the main vehicle of infection was cold foods prepared by a food handler during and after a mild gastrointestinal illness. He was excreting Norwalk-like virus particles 48 hours after the illness. In addition, ill kitchen staff vomited in the kitchen area and may have contaminated surfaces and stored foods. It is recommended that food handlers should be regarded as potentially infectious until at least 48 hours after clinical recovery from viral gastroenteritis. Stored foods that may have been contaminated should be immediately discarded and areas of the work place which may have been affected should be identified and decontaminated. PMID- 2899730 TI - Nuclear threat and health in the Pacific Ocean. PMID- 2899731 TI - EEC supranational drug regulatory authority by 1992? PMID- 2899732 TI - The academic task. PMID- 2899733 TI - Bone-marrow transplantation for sickle-cell anaemia. PMID- 2899734 TI - Indications for pulmonary embolectomy. PMID- 2899736 TI - Neurofibromatosis. PMID- 2899735 TI - Octadeca-9-11-dienoic acid in diagnosis of cervical intraepithelial neoplasia. PMID- 2899738 TI - Laboratory-acquired mycobacterial infection. PMID- 2899737 TI - New inhibitor of platelet aggregation in onion oil. PMID- 2899739 TI - Lung function tests in survivors of the piper alpha oil-platform disaster. PMID- 2899740 TI - IVF surrogacy and absent uterus syndromes. PMID- 2899741 TI - Withholding intensive care from premature babies. PMID- 2899742 TI - Toxicity of cyclosporin metabolites. PMID- 2899743 TI - Quality of life on angina therapy. PMID- 2899744 TI - Effect of oral folate on duration of acute infantile diarrhoea. PMID- 2899746 TI - Oral contraceptives and gallstones. PMID- 2899745 TI - Can children's intelligence be increased by vitamin and mineral supplements? PMID- 2899747 TI - Almitrine and peripheral neuropathy. PMID- 2899748 TI - Open access mammography. PMID- 2899749 TI - Finding alternatives to benzodiazepines. PMID- 2899750 TI - Carnitine and gangliosides. PMID- 2899751 TI - Clobazam in chronic epilepsy. PMID- 2899752 TI - Renoir and Monet. PMID- 2899753 TI - "Doctor" in Europe. PMID- 2899754 TI - Birth control vaccine. PMID- 2899755 TI - Continuing problems in the National Health Service. PMID- 2899756 TI - Odds ratios and relative risks. PMID- 2899757 TI - Academic freedom and the MRC. PMID- 2899758 TI - Urethral lubrication and trauma, a possible mechanism. PMID- 2899759 TI - Acetylcholine sweatspot test. PMID- 2899760 TI - Haptoglobin to protect against renal damage from ethanolamine oleate sclerosant. PMID- 2899761 TI - Delayed CSF reaction to praziquantel. PMID- 2899762 TI - Acyclovir-resistant herpes in AIDS treated with foscarnet. PMID- 2899763 TI - HLA haplotype and HIV infection. PMID- 2899764 TI - Could platelet-derived growth factor have a role in the pathogenesis of lupus nephritis? PMID- 2899766 TI - Chloramphenicol-resistant Haemophilus ducreyi in southern Africa. PMID- 2899765 TI - Hyperinsulinaemia and hypertension in diabetes. PMID- 2899767 TI - Treatment of menopausal symptoms in breast cancer patients. PMID- 2899768 TI - Endotoxaemia in neutropenic patients. PMID- 2899769 TI - Surgery, tamoxifen, and breast cancer in the elderly. PMID- 2899771 TI - BMA advice on insurance AIDS tests. PMID- 2899770 TI - Surgical lesions, parkinsonism, and brain graft operations. PMID- 2899772 TI - Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. AB - 17,187 patients entering 417 hospitals up to 24 hours (median 5 hours) after the onset of suspected acute myocardial infarction were randomised, with placebo control, between: (i) a 1-hour intravenous infusion of 1.5 MU of streptokinase; (ii) one month of 160 mg/day enteric-coated aspirin; (iii) both active treatments; or (iv) neither. Streptokinase alone and aspirin alone each produced a highly significant reduction in 5-week vascular mortality: 791/8592 (9.2%) among patients allocated streptokinase infusion vs 1029/8595 (12.0%) among those allocated placebo infusion (odds reduction: 25% SD 4; 2p less than 0.00001); 804/8587 (9.4%) vascular deaths among patients allocated aspirin tablets vs 1016/8600 (11.8%) among those allocated placebo tablets (odds reduction: 23% SD 4; 2p less than 0.00001). The combination of streptokinase and aspirin was significantly (2p less than 0.0001) better than either agent alone. Their separate effects on vascular deaths appeared to be additive: 343/4292 (8.0%) among patients allocated both active agents vs 568/4300 (13.2%) among those allocated neither (odds reduction: 42% SD 5; 95% confidence limits 34-50%). There was evidence of benefit from each agent even for patients treated late after pain onset (odds reductions at 0-4, 5-12, and 13-24 hours: 35% SD 6, 16% SD 7, and 21% SD 12 for streptokinase alone; 25% SD 7, 21% SD 7, and 21% SD 12 for aspirin alone; and 53% SD 8, 32% SD 9, and 38% SD 15 for the combination of streptokinase and aspirin). Streptokinase was associated with an excess of bleeds requiring transfusion (0.5% vs 0.2%) and of confirmed cerebral haemorrhage (0.1% vs 0.0%), but with fewer other strokes (0.6% vs 0.8%). These "other" strokes may have included a few undiagnosed cerebral haemorrhages, but still there was no increase in total strokes (0.7% streptokinase vs 0.8% placebo infusion). Aspirin significantly reduced non-fatal reinfarction (1.0% vs 2.0%) and non-fatal stroke (0.3% vs 0.6%), and was not associated with any significant increase in cerebral haemorrhage or in bleeds requiring transfusion. An excess of non-fatal reinfarction was reported when streptokinase was used alone, but this appeared to be entirely avoided by the addition of aspirin. Those allocated the combination of streptokinase and aspirin had significantly fewer reinfarctions (1.8% vs 2.9%), strokes (0.6% vs 1.1%), and deaths (8.0% vs 13.2%) than those allocated neither. The differences in vascular and in all-cause mortality produced by streptokinase and by aspirin remain highly significant (2p less than 0.001 for each) after the median of 15 months of follow-up thus far available. PMID- 2899773 TI - Risk-benefit ratio of sodium fluoride treatment in primary vertebral osteoporosis. AB - The risk-benefit ratio of combined fluoride-calcium therapy in primary vertebral osteoporosis was examined prospectively in patients with at least one vertebral fracture. 257 patients were randomised to receive sodium fluoride 25 mg twice daily plus elemental calcium 1 g daily and a vitamin D2 supplement, and 209 received one of the alternative therapies usually prescribed in France. After a follow-up of 24 months the fluoride-calcium group showed a significantly lower rate of new vertebral fractures, the main adverse effect of the regimen being a higher incidence of osteoarticular pains in the ankle and foot; the risk of non vertebral fractures was not increased, and digestive disorders arose with equal frequency in the two groups. Sodium fluoride 50 mg daily seems to represent a reasonable compromise in terms of anti-fracture effectiveness and side-effects. PMID- 2899774 TI - Infant feeding and childhood cancer. AB - A case-control study was used to assess whether inadequate exposure to the immunological benefits of human milk may affect infants' response to infection and make them more susceptible to childhood malignancies. 201 Denver children with cancer diagnosed at 1.5-15 years of age were compared with 181 controls, who were selected to be similar to cases for age, sex, and area of residence. Infant feeding categories were: breast feeding (BF) greater than 6 months; BF less than or equal to 6 months; and artificial feeding (AF, or exclusive non-human milk feeding). Compared with BF greater than 6 months, a raised risk for total cancers was found in both BF less than or equal to 6 month and AF groups. This increased risk was largely due to an increased incidence of lymphoma (n = 26). PMID- 2899775 TI - Association of genetic variant of the glucose transporter with non-insulin dependent diabetes mellitus. AB - A DNA sequence polymorphism, revealed by digestion of genomic DNA with the endonuclease Xba1 and hybridisation with a complementary DNA clone for a human glucose transporter, yields two alleles (sizes 6.2 kbp, the X1 allele; or 5.9 kbp, the X2 allele). The genotype frequencies were investigated in three non insulin-dependent diabetic populations. The frequencies (%) of X1.X1, X1.X2, and X2.X2 were 13, 51, and 36 among 89 North European diabetic subjects, and 8, 38, 54 among their 104 controls (chi 2 test p less than 0.02; G-test p less than 0.02). For 53 South European diabetic patients the frequencies were 19, 50, 31, and for their 41 controls they were 2, 58, 40 (chi 2 test p less than 0.02; G test p less than 0.01). The corresponding figures were 6, 55, 39 for 45 Japanese patients and 0, 28, 72 for a further 49 controls (chi 2 test p less than 0.01; G test p less than 0.001). The occurrence of the association of the X1 allele with diabetes in three separate populations suggests that the polymorphic site may be close to a diabetogenic locus on chromosome 1. PMID- 2899776 TI - Severe premenstrual exacerbations of asthma: effect of intramuscular progesterone. AB - Three patients with severe premenstrual exacerbations of asthma are reported. None had responded to conventional treatment, including high-dose corticosteroids. In all cases there was a striking fall premenstrually in peak flow rate. The addition of intramuscular progesterone (100 mg daily in two cases and 600 mg twice a week in one) to the regimen eliminated the premenstrual dips in peak flow, and daily doses of prednisolone were reduced in the three patients. PMID- 2899777 TI - Treatment of syndromes or of symptoms in psychiatry? PMID- 2899778 TI - Progression of chronic renal failure. PMID- 2899779 TI - Prognosis of psoriatic arthritis. PMID- 2899780 TI - Bovine somatotropin and human health. PMID- 2899781 TI - Imipenem/cilastatin. PMID- 2899782 TI - Self-measurement of blood pressure. PMID- 2899783 TI - School screening for scoliosis. PMID- 2899784 TI - Trial of anonymous versus confidential human immunodeficiency virus testing. AB - Before December, 1986, all public human immunodeficiency virus (HIV) testing in Oregon was done confidentially (using names). In December, clients were offered the option of either anonymous or confidential services. As judged by questionnaire responses, the availability of anonymity increased overall demand for testing by 50%: 125% for homosexual/bisexual (gay) men, 56% for female prostitutes, 17% for intravenous drug users, and 32% for other clients. The number of gay clients who had tests increased from a mean of 42 per month during the 4 months before anonymity was available to 108 per month during the 4 months after, whereas, at public sites in Colorado or California and private sites in Oregon, the number of gay clients tested did not increase. Twice as many seropositive persons were identified during the 3 1/2 months after anonymity became available (n = 85) as in the 3 1/2 months before (n = 36). Thus, availability of anonymous HIV testing and counselling drew gay men who had not sought services under a confidential testing system. PMID- 2899786 TI - The enemy system. PMID- 2899785 TI - Colic, "overfeeding", and symptoms of lactose malabsorption in the breast-fed baby: a possible artifact of feed management? AB - Curtailing the time for which a baby feeds at the first breast, in order to encourage intake from the second breast, may maximise milk production by the mother. With escalation of this situation a point may be reached at which the infant, because of the constraint of his stomach capacity, is unable to consume sufficient calories at a feed, since foremilk is lower in calories than hindmilk. The result will be symptoms of hunger (crying, fretfulness) and maybe even failure to thrive. The low fat content of the diet may cause rapid gastric emptying. This in turn may lead to lactose reaching the small bowel in concentrations that may tax the infant's lactase potential, with resulting diarrhoea. A simple change in breastfeeding patterns may alleviate some instances of undernutrition or diarrhoea. PMID- 2899788 TI - Time trends in juvenile-onset diabetes. PMID- 2899787 TI - Midazolam antagonism. PMID- 2899789 TI - Hyperlipidaemia after renal transplantation. PMID- 2899790 TI - Ultrasound and pyloric stenosis. PMID- 2899792 TI - Oestrogen implant overdose. PMID- 2899791 TI - Abnormal cortisol response in Alzheimer's disease linked to hippocampal atrophy. PMID- 2899793 TI - Motoneuron disease and past poliomyelitis. PMID- 2899794 TI - Potency of ergometrine in tropical countries. PMID- 2899795 TI - Ceftriaxone in relapsing fever. PMID- 2899796 TI - Risk to UK heterosexuals of contracting AIDS abroad. PMID- 2899797 TI - HIV monitoring via general practice. PMID- 2899798 TI - HIV testing without permission. PMID- 2899799 TI - Fall in human herpesvirus 6 seropositivity with age. PMID- 2899800 TI - Antibody to human herpesvirus 6 in HIV-1 positive and negative homosexual men. PMID- 2899801 TI - Dippers and non-dippers. PMID- 2899802 TI - Prenatal diagnosis at 6 weeks. PMID- 2899803 TI - Child abuse after Cleveland. PMID- 2899804 TI - Cytology services. PMID- 2899805 TI - Categories of drug allergy. PMID- 2899806 TI - Inactive ingredients in medicines. PMID- 2899807 TI - T-lymphocyte activation and allergy. PMID- 2899808 TI - In-vitro production of human platelets. PMID- 2899809 TI - Rectal sucralfate in radiation proctitis. PMID- 2899810 TI - Syncope while vomiting during migraine attack. PMID- 2899811 TI - Digitalis: still under suspicion? PMID- 2899812 TI - Safety of mianserin. PMID- 2899813 TI - Acute viral hepatitis 5 years after start of vaccination campaign in Zurich. PMID- 2899814 TI - Tumour necrosis factor and hairy cell leukaemia. PMID- 2899815 TI - Biological differences in the three major leukaemias. PMID- 2899816 TI - Recombinant interferon-alpha for treatment of polycythaemia vera. PMID- 2899817 TI - Release of PAF-acether and precursors during allergic cutaneous reactions. PMID- 2899818 TI - Fluctuating serum cholesterol: implications for coronary prevention. PMID- 2899819 TI - Lipoprotein (a) and coronary heart disease in familial hypercholesterolaemia. PMID- 2899820 TI - Prevention of post-transfusion infectious complications. PMID- 2899821 TI - Subcutaneous erythropoietin. PMID- 2899822 TI - General Medical Council Tests and Race Relations Act. PMID- 2899823 TI - Safety of blood products for haemophilia patients. PMID- 2899824 TI - [The jellyfish (Pelagia noctiluca) as a health problem in the Adriatic and Mediterranean Seas]. PMID- 2899825 TI - Nicotine enhances delayed matching-to-sample performance by primates. AB - The non-human primate provides an excellent model for studies of learning and memory, and one particular test, the delayed matching-to-sample task, is performed in a similar manner by both humans and non-human primates. Five young adult macaques were employed in this study, displaying variable capacities for retention in the task. Baseline performance was very consistent and three levels of performance difficulties (95-100%, 80-85% and 65-75% correct choices) were employed by including several delay intervals (0-60 sec) in each session. A reproducible enhancement in performance by nicotine in macaques performing a delayed matching-to-sample task was demonstrated. Nicotine enhanced performance with an average increase of 10% at the longest retention delay interval. This beneficial effect of nicotine was abolished in animals pretreated with a low dose (0.5 mg/kg) of mecamylamine to block central nicotinic receptors. Selective blockade of peripheral nicotinic receptors with hexamethonium was without effect on the nicotine response. A high dose (2 mg/kg) of mecamylamine itself induced a marked inhibition of performance, while an equivalent dose of hexamethonium was without effect. These experiments point to the possibility that central nicotinic receptors may be exploited pharmacologically to enhance memory performance. In this respect it is interesting that nicotine was most effective at enhancing performance when recall was more difficult, that is, on the longer retention interval delays. This could signify that nicotine might be particularly effective in the most impaired individuals. Lastly, it is encouraging that the mecamylamine induced decrease in cognitive performance might provide a new model of memory impairment from which to study the pathogenesis and develop new pharmacological strategies for the dementias. PMID- 2899826 TI - Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. AB - In vitro binding affinities of chlorpromazine, fluphenazine, levomepromazine, perphenazine and some of their metabolites for dopamine D2 receptors, alpha 1- and alpha 2 adrenoceptors in rat brain were previously reported from our laboratories. The present study reports the in vitro binding affinities of the same compounds for muscarinic cholinergic receptors and for histamine H1 receptors in rat brain, using 3H-quinuclidinyl benzilate and 3H-mepyramine as radioligands. Chlorpromazine, levomepromazine, and their metabolites had 5-30 times higher binding affinities for muscarinic cholinergic receptors than fluphenazine, perphenazine and their metabolites. Levomepromazine was the most potent and fluphenazine the least potent of the four drugs in histamine H1 receptor binding. 7-Hydroxy levomepromazine, 3-hydroxy levomepromazine and 7 hydroxy fluphenazine had only 10% of the potency of the parent drug in histamine H1 receptor binding, while the 7-hydroxy-metabolites of chlorpromazine and perphenazine had about 75% of the potency of the parent drug in this binding system. Their histamine H1 receptor binding affinities indicate that metabolites may contribute to the sedative effects of chlorpromazine and levomepromazine. PMID- 2899827 TI - Suncus murinus as a new experimental model for motion sickness. AB - Characteristics of motion sickness and effects of possible prophylactic drugs were studied using Suncus murinus (house musk shrew) for its potential use as an experimental model in motion sickness. Mild reciprocal shaking (amplitude: 10-40 mm; frequency: 0.5-3.0 Hz) induced vomiting in most of Suncus murinus within 2 min. Adaptation was observed when the motion stimulus was repeated with an interval of 2 to 3 days. During the repetitive motion training, both the ratio of sensitive animals and the number of vomiting episodes decreased, and the time from the start of shaking to the first vomiting was extended. Subcutaneous injection of scopolamine (100 mg/kg), chlorpromazine (8 mg/kg), promethazine (50 mg/kg), diphenhydramine (20 mg/kg), chlorphenylamine (20 mg/kg) and methamphetamine (2 mg/kg) decreased the emetic effect of motion sickness, but pyrilamine (20 mg/kg), meclizine (20 mg/kg) and dimenhydrinate (32 mg/kg) were not effective or very weak. These results indicate that the Suncus murinus is sensitive to the motion stimulus and antiemetic drugs are effective as prophylaxis. The Suncus murinus is useful as a new experimental animal model for motion sickness. PMID- 2899828 TI - High affinity binding of [125I-Tyr11]somatostatin-14 to human small cell lung carcinoma (NCI-H69). AB - The in vitro binding of [125I-Tyr11]somatostatin-14 (SRIF-14) to membranes prepared from cultured human small cell lung carcinoma (SCLC) cells (NCI-H69) has been characterized. Binding to SCLC was monophasic and of high affinity (Kd = 0.59 +/- 0.02 nM, n = 3). The estimated Bmax was 173 +/- 2.4 fmol/mg protein. Receptors were also present on solid NCI-H69 tumors grown in vivo in the athymic nude mouse. However, the concentration was only about 10% of that observed in cell culture. Biologically-active SRIF analogues were potent inhibitors of [125I Tyr11]SRIF-14 binding, and an analysis of the pharmacological specificity indicated that the SCLC receptor was of the peripheral (e.g., non-neural) subtype. The presence of SRIF receptors on SCLC membranes may indicate that SRIF has a role in regulation of SCLC function. PMID- 2899829 TI - Stable analogs of acyl adenylates. Inhibition of acetyl- and acyl-CoA synthetase by adenosine 5'-alkylphosphates. AB - Adenosine 5'-alkylphosphates are potent inhibitors of acetyl- and acyl-CoA synthetase. In each case, the most effective inhibitor in the series is homologous with the tightly bound acyl adenylate intermediate. Adenosine 5' ethylphosphate (Ki = 33 nM) is 88-fold more potent than adenosine 5' methylphosphate (Ki = 2900 nM) as a competitive inhibitor of acetyl-CoA synthetase; the contribution of a single carbon to the observed binding energy ( 11 kJ/mol) is much larger than is typically observed. PMID- 2899830 TI - Flow dependent changes in the effective surface area of microdialysis probes. AB - The relative efficiencies of microdialysis probes were determined both in vitro and in vivo using tritiated water. Tritiated water (THO) freely distributes throughout the fluid spaces of an experimental animal and, at equilibrium, the brain extracellular concentration of THO is the same as the plasma concentration. Microdialysis probes were inserted into the right caudoputamen of anesthetized rats. The rats were injected with THO and after one hour microdialysis samples were collected at flow rates between 0.2 and 10.0 ul/min. The in vitro relative efficiency for THO was computed as the ratio of the THO concentration in the dialysate to that of the solution the probe was immersed in. The in vivo relative efficiency was computed as the ratio of the concentration of THO in the brain dialysate to that measured in the plasma of the rat. Both the in vitro and in vivo relative efficiencies for THO decrease with increasing flow rates, but they differ from each other except at very low flow rates (less than 0.25 ul/min). The in vitro relative efficiency at a given probe flow is the maximum efficiency that can be attained in vivo at that flow. The surface of effective exchange (Se) is the fraction of that maximum which is attained in vivo. This study also demonstrates how the effective surface area can be computed at any probe flow rate and how it can be used as a correction factor. PMID- 2899832 TI - Midgestational exposure of pregnant BALB/c mice to magnetic resonance imaging conditions. AB - The potential for producing reproductive toxicity or teratogenesis in mice by exposure to magnetic resonance imaging (MRI) conditions was evaluated by means of reproduction studies and the homeotic shift test. Embryos from pregnant BALB/c mice were exposed in vivo for 16 hours beginning on gestation day 8.75 to MRI conditions of modest field strength (static field, 0.35 tesla (T); pulsed gradients, 2.3 X 10(-4) T/cm for 2.5 to 10 msec; and radio frequency, 15 MHz at an average of 61.2 mW). Unexposed, sham-exposed (both MRI and X-ray) and X irradiated (0.5 Gy) animals were the control groups. Neither placental resorptions nor stillbirths were increased by MRI. Fetal weight at birth and crown-rump length were proportional; however, crown-rump length was significantly less (p less than 0.001) in the MRI-exposed fetuses (respective mean values for MRI-exposed fetuses were 21.8 +/- 0.2 mm compared to 22.4 +/- 0.1 for sham exposed fetuses). Both crown-rump length and fetal weight were significantly reduced after X-irradiation. The percentage of homeotic skeletal shifts was scored for each of eight anatomic sites. Only X-radiation produced significant increases in skeletal shifts. Prolonged midgestational exposure of mice to MRI conditions currently used for human clinical imaging, therefore, failed to reveal overt embryotoxicity (resorptions, stillbirths) or teratogenicity (homeotic shifts), consistent with the non-ionizing properties of MR. However, the slight but significant reduction in fetal crown-rump length after prolonged exposure justifies further study of higher MRI energy levels and consideration of other endpoints for establishing with greater confidence the safety of MRI during pregnancy. PMID- 2899831 TI - Attenuation of growth hormone gene expression in desensitized somatotropes. AB - The effects of GRF-induced desensitization of somatotropes on GH gene expression were investigated on pituitary cells derived from male rats. Pretreatment of monodispersed cells for 18 hr with GRF abolished both the acute release of GH and the stimulation of GH gene expression in response to a subsequent 4 hr challenge with GRF. Concomitant preincubation with GRF and SS resulted in restoration of the ability of GRF to stimulate release of GH but not to augment GH gene expression. These results demonstrate that desensitization by GRF affects both the release of GH and GH gene expression, whereas the resensitizing effects of SS appear to be directed exclusively at the release mechanism. PMID- 2899833 TI - Serum amyloid A (SAA) gene variations in familial Mediterranean fever. AB - Novel structural changes in members of the serum amyloid A (SAA) gene family have been found in four patients of varied ethnic backgrounds with familial Mediterranean fever. Since the genes for these small acute phase proteins are generally well conserved, these observations suggest that alterations of serum amyloid A genes, their protein products and/or their regulation may be responsible for familial Mediterranean fever. PMID- 2899834 TI - The "Irukandji syndrome" and acute pulmonary oedema. PMID- 2899835 TI - Nizatidine (AXID). PMID- 2899836 TI - Purification and properties of the Drosophila zen protein. AB - The zen protein is encoded by the zerknullt gene required for normal early development in Drosophila. Like many regulatory proteins of this type, zen contains a 60 amino acid homeobox sequence. We have purified the zen protein and studied its solution behavior and its interaction with DNA. The zen protein exists as a monomer in solution with a molecular weight of about 40,000. It binds specifically to a site about 900 bases upstream from the zen gene. Within this binding site DNase protection experiments indicate that binding is confined to two regions approximately 11 and 14 bases in length that are separated by about 30 base pairs. The protein concentration dependence of the binding curve suggests that protein binding is non cooperative. PMID- 2899838 TI - Molecular analysis of membrane gamma 2b heavy chain expression. AB - In order to study T cell regulation of B cell isotype differentiation we have developed a model system consisting of clonal populations of T and B cells. Using this system we have shown that the murine B cell lymphoma, 70Z/3, can be induced to express membrane IgG2b by exposure to a T cell hybridoma derived from the Peyer's patch (termed HAJ-3). The membrane bound IgG2b (mIgG2b) expression is associated with induction of gamma 2b-mRNA, but switch region rearrangement and C mu deletion does not occur. While LPS-stimulated 70Z/3 B cells also express considerable amounts of gamma 2b-mRNA they do not express detectable mIgG2b, indicating that T cell influence is necessary for the production of translatable gamma 2b-specific mRNA. Both the LPS and T cell induced gamma 2b mRNA transcripts lack VH sequences, implying that the surface IgG2b detected lacks a variable region. These findings lend support to a two step model of B cell isotype switching and provide evidence that T cells can regulate early events involved in B cell isotype differentiation. PMID- 2899837 TI - Structure and evolution of somatostatin genes. AB - A bovine pancreatic preprosomatostatin cDNA clone has been isolated and sequenced. Although it encodes a predicted 116 amino acid preprosomatostatin that is very similar in primary structure to those deduced from other mammalian preprosomatostatin cDNAs, there are some differences in amino acid composition. Hybridization of this clone to Northern blots of fetal bovine pancreatic poly(A+) RNA reveals a mRNA of 700 nucleotides. Evolution of the preprosomatostatin genes was studied by statistical analysis of anglerfish, catfish, bovine, rat, and human cDNA sequences. The results suggest that the two somatostatin genes present in both anglerfish and catfish were the result of a gene duplication event in a common ancestor of anglerfish and catfish. PMID- 2899839 TI - HLA-DR and DQ DNA polymorphisms in subjects of Asian Indian and white Caucasian origin. AB - There is a close correspondence between serologically defined DR types and DR beta chain restriction fragment length polymorphisms (RFLPs). There is also an association between DR types and DQ alpha and DQ beta RFLPs because of linkage disequilibrium. We present the results of an analysis of DR beta, DQ alpha and DQ beta RFLPs in Asian Indians and white Caucasian subjects. DR beta RFLPs were similar in the two groups. Clearly distinguishable DR beta patterns were observed for DR1, 2, 3, 4, 5, 7 and w10. The DR beta patterns associated with DR3 were, however, also found with w6. The DR7 DR beta patterns were also found with w9. For DR specificities 1, 3, 4, 5, 7 and w10, the associated DQ alpha and DQ beta RFLPs were similar in both racial groups, but for DR2, however, marked differences were found. The DR2-positive white Caucasian subjects all possessed a single DQ alpha/DQ beta combination whereas the DQ alpha/DQ beta patterns in DR2 positive Asian Indians showed considerable heterogeneity. The pattern seen in white subjects was present in only a minority of Asians. DR-DQ relationships clearly vary in different racial groups. RFLP analysis of HLA-linked diseases in different populations should prove to be an important technique in identifying the primary genetic factor(s) in these disorders. PMID- 2899841 TI - Localization and seizure-induced alterations of opioid peptides and CCK in the hippocampus. PMID- 2899840 TI - The effect of diltiazem on mortality and reinfarction after myocardial infarction. AB - We studied the effect of diltiazem on mortality and reinfarction in 2466 patients with previous infarction from 38 hospitals in the United States and Canada. The patients were randomly assigned to receive diltiazem (240 mg per day, n = 1234) or placebo (n = 1232) and followed for 12 to 52 months (mean, 25). Total mortality rates were nearly identical among the two treatment groups (167 and 166, respectively), as were cumulative mortality rates. There were 11 percent fewer first recurrent cardiac events (death from cardiac causes or nonfatal reinfarction) in the diltiazem group than in the placebo group (202 vs. 226; Cox hazard ratio, 0.90; 95 percent confidence limits, 0.74 and 1.08). A significant (P = 0.0042) bidirectional interaction between diltiazem and pulmonary congestion was observed on x-ray examination. In 1909 patients without pulmonary congestion, diltiazem was associated with a reduced number of cardiac events (hazard ratio, 0.77; 95 percent confidence limits, 0.61 and 0.98); in 490 patients with pulmonary congestion, diltiazem was associated with an increased number of cardiac events (hazard ratio, 1.41; 95 percent confidence limits, 1.01 and 1.96). A similar pattern was observed with respect to the ejection fraction, which was dichotomized at 0.40. Thus, diltiazem exerted no overall effect on mortality or cardiac events in this population of patients with previous infarction. This neutral effect reflected a diltiazem-related reduction in cardiac events in the majority of patients without left ventricular dysfunction and an increase in such events in the minority of patients with left ventricular dysfunction. PMID- 2899842 TI - Seizure-induced alterations in the metabolism of hippocampal opioid peptides suggest opioid modulation of seizure-related behaviors. AB - The evidence accumulated so far indicates that seizure activity exerts profound changes on the metabolism of opioid peptides in the hippocampus. Our data consistently show a large transient decrease in dynorphin and a modest decrease in enkephalin in the hippocampus following either a single ECS or KA injection. These initial reductions, which are indicative of increased release, may trigger the biosynthetic process of hippocampal opioids and result in an overproduction of the peptides seen in the rebound phase. However, the amount and timing of the rebound in enkephalin and dynorphin levels in response to repeated ECS, amygdaloid kindling, or KA differ drastically: a rapid and sustained increase in ME-LI follows all three treatments, in contrast to a slow recovery after a large and sustained decrease in DN-LI induced by repeated ECS and amygdaloid kindling. These results, which are unique to the hippocampus, suggest that differential mechanisms are operative in regulating the metabolism of these two opioid peptides in the hippocampus. It is likely that a well-coordinated regulation of hippocampal function can be achieved through the differential release of enkephalin and dynorphin and their subsequent interactions at different subtypes of opioid receptors following seizure activities. From a functional point of view, our data provide a neurochemical correlate of previous reports that brain opioid peptides may mediate ECS-induced behavioral alterations, such as changes in seizure threshold, postictal depression, and retrograde amnesia. The robust changes in the levels of opioid peptides in kindled rats, plus shortening of the kindling process by pretreatment with mu opioid antagonists, strongly suggest the involvement of brain opioid peptides in the development of kindling. Finally, these studies show clear evidence that enkephalin in the hippocampus is important in KA-induced WDS, a component of the opiate withdrawal syndrome in rodents (Isaacson and Lanthorn 1981). Further studies should help distinguish the regulatory mechanisms responsible for changes in opioid peptide metabolism during states of hyperexcitability in the hippocampal formation. PMID- 2899843 TI - Opioid receptor mechanisms in the rat hippocampus. PMID- 2899845 TI - [Depression in Parkinson disease]. PMID- 2899844 TI - Mapping of mutation causing Friedreich's ataxia to human chromosome 9. AB - Friedreich's ataxia is an autosomal recessive disease with progressive degeneration of the central and peripheral nervous system. The biochemical abnormality underlying the disorder has not been identified. Prompted by the success in localizing the mutations causing Duchenne muscular dystrophy, Huntington's disease and cystic fibrosis, we have undertaken molecular genetic linkage studies to determine the chromosomal site of the Friedreich's ataxia mutation as an initial step towards the isolation and characterization of the defective gene. We report the assignment of the gene mutation for this disorder to chromosome 9p22-CEN by genetic linkage to an anonymous DNA marker MCT112 and the interferon-beta gene probe. In contrast to the clinical variation seen for the disorder, no evidence of genetic heterogeneity is observed. PMID- 2899846 TI - [Benzodiazepine receptors in the central nervous system of mammals]. AB - The review describes benzodiazepine receptor in CNS of mammalians. There are two types of benzodiazepine receptors--"central" and "peripheral" with different pharmacological properties. Besides, it is possible to consider that "central" benzodiazepine receptors are not homogeneous, and are presented by two populations which fulfil different physiological role. PMID- 2899847 TI - Age-related changes in growth hormone releasing factor and somatostatin in the rat hypothalamus. AB - Distribution and staining intensities of growth hormone releasing factor (GR (GRF) and somatostatin (SRIF) were examined in young (3 months of age) and old (24 months of age) male rats of Sprague-Dawley strain, using the PAP immunocytochemical procedure. Some animals of each age group were intraventricularly injected with colchicine to demonstrate immunoreactive neuronal perikarya. GRF-immunoreactive intensities of old rats were markedly reduced in the median eminence as compared with those of young rats. No remarkable difference could be detected between SRIF immunoreactivities in the young and old animals, since intensive SRIF immunoreactivities were found in the external layer of the median eminence of both groups of animals. Between two age groups injected with colchicine, we also found no difference in the distribution and staining intensities of immunoreactive perikarya of GRF and SRIF in the hypothalamus and also detected no significant difference in total neuron numbers of each peptide. These findings suggest that the synthesis and/or release of GRF in GRF-containing neurons are decreased, though GRF-containing neurons themselves remain alive and have the capacity to synthesize GRF. PMID- 2899848 TI - Relationship of alpha-1- and alpha-2-adrenergic-binding sites to regions of the paraventricular nucleus of the hypothalamus containing corticotropin-releasing factor and vasopressin neurons. AB - To investigate catecholamine regulation of adrenocorticotropic hormone (ACTH) and vasopressin (VP) release, the relationship of alpha-adrenergic receptor-binding sites to corticotropin-releasing factor (CRF) and VP-containing cell populations within the paraventricular nucleus (PVN) of the hypothalamus was studied. Immunohistochemistry for CRF and neurophysin-vasopressin (NP-VP) was combined with receptor autoradiography. The adrenergic antagonist [3H]-prazosin was used to visualize alpha-1-binding sites and the agonist [3H]-p-aminoclonidine to visualize alpha-2-binding sites. To determine if changes in adrenergic binding accompanied experimentally induced increased activity of CRF- and VP-containing neurons, adrenalectomy was used as a stimulus for CRF release and dehydration as a stimulus for VP release. Quantitative assessment of autoradiograms revealed a greater density of alpha-1- and alpha-2-binding sites over the medial, parvocellular, CRF-containing region of PVN as compared to the lateral, magnocellular, NP-VP-containing region of the nucleus in all animal groups. Following 10 days of dehydration, the density of alpha-1- and alpha-2-binding sites associated with the CRF- and NP-VP-containing regions of PVN decreased. At 14 days postadrenalectomy the density of alpha-2-binding sites associated with CRF- and NP-VP-containing regions of the nucleus decreased, but the density of alpha-1-binding sites was unchanged. Results of this study support the hypothesis that epinephrine and/or norepinephrine regulate the release of ACTH and vasopressin via alpha-1- and alpha-2-adrenergic receptors associated with CRF- and VP-containing somata within the PVN. PMID- 2899849 TI - Somatostatin-28 effects on central nervous system regulation of vasopressin secretion and blood pressure. AB - Somatostatin-28 (SS-28) acted within the central nervous system (CNS) to produce a dose-dependent elevation of mean arterial pressure (MAP), a reduction of heart rate (HR), and an elevation of the plasma concentration of vasopressin. SS-28 given intravenously did not affect MAP or HR. Furthermore, these changes of cardiovascular functions were not prevented by systemic passive immunization against SS-28, thus supporting a CNS site of action. Microinjections of SS-28, in amounts ineffective when given into the lateral cerebroventricle or other brain parenchymal areas, into the paraventricular nucleus of the hypothalamus produced significant elevations of MAP. Neither ganglionic blockade with chlorisondamine nor treatment with the alpha-adrenergic receptor antagonist, phentolamine, prevented SS-28-induced changes of cardiovascular function; however, treatment of animals with the vasopressin antagonist [1-deaminopenicillamine, 2-(0-methyl)Tyr] vasopressin completely prevented SS-28-induced elevation of MAP and slowing of HR. These results suggest that SS-28 acts within the CNS to increase MAP and decrease HR by stimulating pituitary vasopressin secretion. PMID- 2899850 TI - Superior protective effects of phenytoin against hypoxia in a pharmacological screening test. AB - The selection of drugs to prevent the development of pathology in cerebral infarction remains an important problem. For the selection of effective drugs from among a large number of possible candidates, widely-used test screening techniques are sufficient for obtaining a good understanding of candidate drug effects. The effects of various drugs on the survival time of mice made hypoxic by exposure to a 4% O2-96% N2 gas have been examined. The survival time of 110 control animals was 170 +/- 6 s, showing a nearly normal distribution pattern. No control mouse had a survival time beyond 8 min. The survival time after the drugs were administered was as follows: suloctidil (12.5 mg/kg, n = 11), 1833 +/- 487 s; vitamin E (200 mg/kg, n = 15), 1160 +/- 342 s; pentobarbital (50 mg/kg, n = 12), 602 +/- 74 s; and phenytoin (100 mg/kg, n = 10), 2667 +/- 452 s. In contrast, administration of vitamin C, coenzyme Q, cytochrome c, beta-methasone, mannitol or germanium-132 did not result in prolongation of survival time. Comparison of the percentage of animals in each group which survived for more than 1 h showed 0% in the control group, 45.5% in the suloctidil group (12.5 mg/kg), 23.5% in the vitamin E group (200 mg/kg), 0% in the pentobarbital group (50 mg/kg) and 70% in the phenytoin group (100 mg/kg). These findings suggest that phenytoin is the most effective drug in combatting the effects of hypoxia (survival time was expressed as mean +/- SE). PMID- 2899851 TI - Freeze-fracture cytochemistry of cholesterol content in neuronal plasma membrane following cerebral ischaemia. AB - Minor changes on the neuronal perikaryon cytoplasm and large alterations in neuronal processes have been demonstrated with transmission electron microscopy after 60 minutes of focal and selective cerebral ischaemia. The distribution of cholesterol in neuronal plasma membrane and perikarya plasmalemma of normal and ischaemic caudate nucleus was investigated with the polyene antibiotic filipin, a morphological probe for membrane cholesterol domains in freeze-fracture replicas. After filipin incubation of prefixed vibratome slices, filipin-cholesterol complexes appeared as 20-30 proturberances and pits on P- and E-faces. Distinct patterns of filipin-cholesterol complexes were found in non-ischaemic and ischaemic neuronal membrane. The filipin-treated specimens showed a 35-40% drop in cholesterol content in the neuronal plasmalemma one hour after cerebral ischaemia. PMID- 2899852 TI - Regional differences in inhibition and recovery of protein synthesis after transient hindbrain ischaemia of gerbils. AB - Regional protein synthesis was estimated autoradiographically in a model of transient hindbrain ischaemia of gerbils. In studies of 5 min ischaemia followed by 5 min recirculation, incorporation of [14C]valine into the TCA-insoluble protein fraction was not affected. In studies of 15 min ischaemia followed by 5 min recirculation, incorporation of the tracer into the protein fraction was severely depressed in the ischaemic lesion of the brain stem and cerebellum. However, the granular layer of the cerebellar cortex had partially preserved protein synthesis. When recirculation time was extended to 2 h after 30 min ischaemia, protein synthesis of the cerebellar cortex almost recovered to the full level of the control. However, in the pontine grey matter, inferior colliculus and vestibular nucleus, a significant reduction in protein synthesis persisted. These results indicate that protein synthesis in the pontine grey matter, inferior colliculus and vestibular nucleus are selectively inhibited by ischaemia. Further its recovery after recirculation is slow. The cerebellar cortex is less vulnerable to ischaemia, and recovery is relatively fast. The regional heterogeneity of protein synthesis is neither due to the degree of ischaemia in this model nor the extent of postischaemic hypoperfusion. Factors that influence protein synthesis in this ischaemic model are discussed. PMID- 2899853 TI - Revascularization surgery for moyamoya disease. AB - Moyamoya disease is a disease characterized by chronic occlusion of the circle of Willis with subsequent development of fine vascular networks in the ganglionic region, which is common in Japanese people. The term of 'moyamoya' means puff of smoke in the Japanese language and represents the characteristic angiographic findings of subsequent development of fine vascular networks in the ganglionic region. Although reconstructive surgery for moyamoya disease has been widely accepted nowadays, there is still no definite consensus as to a surgical indication for patients with an haemorrhagic attack and as to the selection of an operative method for each individual patient. This paper presents our overall surgical results and introduces a new operation, devised by Y. Nakagawa (i.e. EMAS). It refers also to surgical intervention for patients with haemorrhagic attacks. PMID- 2899854 TI - Neuroradiological study of human brain in the fetal period. AB - Craniocerebral CT scans were performed on 50 subjects including embryos, fetuses and newborns. Fetuses were divided into three stages based upon CT findings. The first stage ranged from the 8th gestational week to the 12th week, and the second stage from the 13th to 23rd week. Beyond 24 gestational weeks, fetuses were classified as the third stage. In the first stage, it is difficult to recognize the intracranial structure on CT scans. In the second stage, the intracranial structures on CT scans become clearer. Around the lateral ventricle a symmetrical high-density area appears, which corresponds to the germinal matrix. However, at the third stage, the high-density area disappears. The morphological changes of the ventricular system with growth are ascribed to a remarkable development of the cerebral parenchyma. PMID- 2899855 TI - Subarachnoid haemorrhage produces differential effects on transmitter kinetics at cerebral periarterial noradrenergic terminals. AB - The functional states of cerebral perivascular noradrenergic terminals were investigated following experimental 'closed-space' subarachnoid haemorrhage (SAH) in cat. The left middle cerebral artery (L-MCA) was compared to the ruptured right (R-MCA) one. Permeability kinetics of 3H-NA (noradrenaline) were measured simultaneously in isolated segments of paired R- and L-MCAs, testing responses to electrical field stimulation and the presence of the alpha-adrenoceptor antagonist, phentolamine, at different concentrations and times post-SAH. Fractional 3H-NA efflux from ruptured R-MCAs was reduced to undetectable levels at 18 h to at least 3 d post-SAH. Response to electrical stimulation partially recovered at 10 d and approached the controls by 16 to 30 d. In the L-MCAs, 3H-NA efflux was decreased up to 90% at 18 h, but recovered to control level by 3 d, unless it too became involved by encroachment of blood from the SAH side. The fractional 3H-NA efflux in the controls was typically augmented by phentolamine, reaching a peak at 0.3 microM of the drug. This overflow response was completely lost between 0.03 and 3.0 microM phentolamine in the R-MCAs for at least 30 d post-SAH, whereas uninvolved L-MCAs regained drug-induced overflow at 10 to 16 d post-SAH. Uptake of 3H-NA after SAH was also decreased 30 to 50% for both MCAs at 18 h and 3 d post-SAH. Control 3H-NA uptake was regained by 10 d post-SAH in the L-MCA but not until 16 d in the R-MCA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899856 TI - Haemodynamic evaluation of the cerebral circulation by periorbital Doppler examination and cerebral blood flow (CBF) measurement in carotid artery disease. AB - To assess the haemodynamic significance of an internal carotid artery (ICA) stenosis, angiography or direct ultrasound examination should be supplemented by indirect physiologic testing of the collateral circulation. Among the tests proposed, we used the periorbital flow direction, assessed by Doppler technique, and cerebral blood flow reactivity to vasodilation, by i.v. xenon-133 technique, in 35 patients before carotid endarterectomy. The results were related to the actual perfusion pressures, measured during surgery in the distal ICA. All 15 patients with normal orthograde periorbital flow had normal cerebral blood flow (CBF) vasoreactivity and no, or only minor, reduction in ICA perfusion pressure. Of the 20 patients with inverted flow, 12 had normal and 8 had abnormal CBF reactivity. These 8 patients proved to have significantly lower cerebral perfusion pressures, as compared with the remaining 12 patients with inverted periorbital flow (p less than 0.001), who in turn had lower perfusion pressures than the 15 patients with orthograde flow (p less than 0.005). Based on these results, we suggest periorbital Doppler examination as a haemodynamic adjunct to direct ICA visualization. A normal orthograde flow will most certainly rule out any severe pressure reduction. By measuring CBF at rest and following vasodilation in cases with inverted flow, most patients with severe reduction in cerebral perfusion pressure may be identified. PMID- 2899857 TI - Middle cerebral artery occlusion in presence of low perfusion pressure increases infarct size in rats. AB - A model was set up in order to evaluate the importance of hemispheric perfusion pressure when the middle cerebral artery (MCA) is occluded in anaesthetized rats. In 6 animals the internal carotid artery (ICA) was occluded prior to ipsilateral MCA occlusion; in 17 animals the MCA only was occluded; 6 animals underwent the same preparation, but the vessels were left unoccluded. Four days after surgery the infarct volume was measured with a computerized image analyser. The infarcted areas were significantly larger in the ICA + MCA occluded group compared with the MCA occluded group (p less than 0.005), which in turn had larger infarcts than the sham-operated animals (p less than 0.001). These results indicate that patients with hypoperfusion, due to severe ICA stenosis and impaired collateral blood supply, are at higher risk of developing major stroke, when embolism into a cerebral artery occurs, as compared to patients with no, or only minor, reduction in hemispheric perfusion pressure. PMID- 2899859 TI - GABAergic innervation of somatostatin-containing neurosecretory cells of the anterior periventricular hypothalamic area: a light and electron microscopy double immunolabelling study. AB - Double immunolabelling on semithin sections revealed glutamate decarboxylase immunopositive dots surrounding somatostatin-containing cell sections in the rat periventricular hypothalamic area. Up to 12 appositions were observed per cell section with an average number of 2-3 and a unimodal distribution. At the electron microscopical level pre-embedding staining of glutamate decarboxylase showed that most immunoreactive elements consisted of immunolabelled axonal endings. Most of these glutamate decarboxylase immunopositive boutons were found within the neuropil where they frequently made synapses on unidentified dendrites. Some of them were apposed to somatostatin-containing cell bodies that were identified according to the presence of immunolabelled granules using combined immunogold post-embedding staining. In many instances glutamate decarboxylase immunoreactive endings were also found to be involved in synaptic contact with somatostatin-labelled perikarya, or neuronal processes. These contacts provide the morphological basis for a direct GABAergic control of the somatostatin-containing cells regulating the secretion of growth hormone. PMID- 2899858 TI - Near-infrared monitoring of cerebral oxygen sufficiency. I. Spectra of cytochrome c oxidase. AB - Near-infrared (NIR) difference spectra were obtained for oxidized cytochrome c oxidase of isolated mitochondria in vitro and of cerebral tissue in situ observed through scalp and skull. The broad peaks of maximal absorption observed in both were not inconsistent with the customary assignment of an 830 nm peak. However, the ratios of the intensity of the NIR band to that of the visible peak (605 nm), which we found to be identical for in-vitro and in-situ spectra, were consistently and significantly higher than those of the various purified enzyme preparations reported in the literature. In addition the half-band widths of our in-vitro and in-situ preparations were narrower. Haemoglobin spectra in the NIR obtained in clear and in highly light-scattering media showed almost total absence of band distortion in this spectral region, suggesting that the differences observed are not due to scattering effects. Anoxia and the specific oxidase inhibitors, cyanide and carbon monoxide, caused the expected disappearance of the band in both the mitochondria in vitro and the cerebrum in situ. The 830 nm band observed in intact, well-oxygenated animal preparations was therefore identified with the NIR absorption band of oxidized cytochrome c oxidase, notwithstanding the differences with the observations on purified preparations. This points to the possibility of developing instrumentation and techniques for the non-invasive monitoring of the redox state of cytochrome c oxidase as an index to cerebral oxygen sufficiency, i.e. adequate delivery and utilization of oxygen to and by brain tissue. PMID- 2899861 TI - Multiple sulfatase deficiency. AB - Multiple sulfatase deficiency is an inherited disorder characterized by a deficiency of several sulfatases and the accumulation of sulfatides, glycosaminoglycans, sphingolipids, and steroid sulfates in tissues and body fluids. The clinical manifestations represent the summation of two diseases: late infantile metachromatic leukodystrophy and mucopolysaccharidosis. We present a 9 year-old girl with a phenotype similar to a mucopolysaccharidosis: short stature, microcephaly, and mild facial dysmorphism, along with dysphagia, retinal degeneration, developmental arrest, and ataxia. We discuss the importance of measuring the sulfatase activities in the leukocytes, and the instability of sulfatases in the cultured skin fibroblasts. PMID- 2899860 TI - Adrenal secretion of catecholamines evoked by chemical stimulation of trigeminal nucleus caudalis in the cat. AB - Microinjections of the neuroexcitatory substance L-glutamate, were made directly into various laminae of trigeminal nucleus caudalis to examine the influence of medullary dorsal horn neurons on the adrenal secretion of catecholamines in the anesthetized cat. Microinjections into the marginal layers (lamina I-II) or into the deep magnocellular portion (lamina V-VI) of nucleus caudalis ipsilateral to the adrenal vein sample evoked a prompt increase in the secretion of epinephrine and a smaller, yet consistent, increase in the secretion of norepinephrine. Injections into the magnocellular layers (lamina III-IV) had no significant effect on secretion of catecholamines. Injections into nucleus caudalis, contralateral to the adrenal vein sample, had no consistent effect on secretion suggesting that the central pathway from nucleus caudalis to the spinal cord for control of adrenal secretion of catecholamines is mainly ipsilateral. Changes in the adrenal secretion of epinephrine were not correlated with changes in adrenal venous blood flow, in arterial pressure or in heart rate. Arterial pressure was transiently increased by L-glutamate injections into the marginal layers, whereas injections into other laminae had no consistent effect. Heart rate increased regardless of the laminar site injection. The results indicate that local excitation of nucleus caudalis, in laminae that contain the majority of nociceptive neurons, evokes a consistent increase in the adrenal secretion of catecholamines, whereas excitation of neurons in laminae that mainly process non noxious sensory input has no significant effect. It is concluded that secondary trigeminal neurons that contribute to the autonomic responses to noxious trigeminal stimuli have a similar distribution within nucleus caudalis as those that underlie the sensory-discriminative aspects of nociceptive. PMID- 2899862 TI - Spontaneous proliferation of peripheral blood lymphocytes increased in patients with HTLV-I-associated myelopathy. AB - We found unstimulated (spontaneous) peripheral blood lymphocyte (PBL) proliferation significantly increased in 14 patients with human T-lymphotropic virus (HTLV)-I-associated myelopathy (HAM) compared with findings in HTLV-I seropositive non-HAM carriers (N = 8) or HTLV-I seronegative controls (N = 16). The proliferative response to phytohemagglutinin, concanavalin A, or pokeweed mitogen was decreased in the HAM patients. Cell clusters were frequent in cultures of unstimulated PBL from the HAM patients, but much less common in the controls or carriers. This spontaneous PBL proliferation was depressed when adherent-cell populations were depleted from the cultures. IL-2 activity increased in the supernatant of 3-day cultured cells from HAM patients, but not in cultured cells from the controls. Since IL-2 receptor positive cells increased in HAM, this spontaneous PBL proliferation is probably a response to IL-2 through the expression of IL-2 receptors. PMID- 2899864 TI - Effects of the NMDA antagonist 2AP5 on complex spike discharge by hippocampal pyramidal cells. AB - The N-methyl-D-aspartate receptor antagonist D,L-2-amino-5-phosphonopentanoate (2AP5) was administered intraventricularly to determine its effect on the complex spike firing pattern of spontaneously active hippocampal pyramidal cells recorded in urethane anaesthetized rats. Following 2AP5 delivery, complex spike firing decreased by a mean 36%, while only a 5% decrease was observed after saline injection. This effect could not be explained by changes in firing rate per se but appeared to be related to the degree of blockade of commissurally induced long-term potentiation. Thus 2AP5 not only disrupts synaptic plasticity in the hippocampus but can also alter the pattern of ongoing activity of the pyramidal cells. PMID- 2899863 TI - Use of the selective benzodiazepine-1 (BZ-1) ligand [3H]2-oxo-quazepam (SCH 15 725) to localize BZ-1 receptors in the rat brain. AB - Receptor autoradiographic techniques have been used to localize benzodiazepine-1 (BZ-1) receptor sites by employing a tritiated form of 2-oxo-quazepam (SCH 15 725), a metabolite of the benzodiazepine quazepam (SCH 16-134). Labeling of the receptors was quantitatively determined to be most abundant in areas of the rat brain known through previous autoradiographic studies to bind preferentially with BZ-1 selective ligands. These areas include lamina IV of the parietal cortex, substantia innominata, anterior amygdaloid nucleus, substantia nigra, zona incerta, and molecular layer of the cerebellum. Autoradiographic localization of binding sites for [3H]2-oxo-quazepam provides additional support for the hypothesis that this compound identifies the BZ-1 receptor subtype and demonstrates the utility of this ligand for quantitation of the distribution and density of these sites. PMID- 2899865 TI - [Meetings for reflexion of the Organizacion Colegial de Enfermeria. Restructuring]. PMID- 2899866 TI - T cell depletion of bone marrow for clinical marrow allografting: optimalization of conditions for depletion by anti-CD2 and anti-CD8 monoclonal antibodies with rabbit complement, and for detection of residual T cell content. AB - Normal bone marrow obtained at harvest for bone marrow transplantation was passed over a Ficoll density gradient to obtain the mononuclear cell fraction. These cells were incubated with anti-T cell monoclonal antibodies (MAb) anti-HuLym-1 and anti-HuLym-8 plus rabbit complement, washed, and the degree of T cell depletion was assessed by culture in phytohemagglutinin, by flow cytometry and by limiting dilution analysis. The optimal protocol for T cell depletion was found to be a 2-stage incubation with 2 cycles of complement treatment, using a bone marrow cell concentration as low as possible. The precise conditions of complement dilution and incubation temperature depended on the batch of complement used, and had to be assessed for each batch. Of the 3 methods used for assessing T cell contamination, culture in PHA was found to be inappropriate due to large variation in background proliferation of treated and untreated bone marrow cells. Flow cytometry was accurate for residual T cell content of greater than 1% (corresponding to a 90-95% depletion of T cells) but could not detect lower levels of T cell contamination. The limit dilution assay was found to be by far the most sensitive, being capable of detecting a T cell contamination of 1 in 10,000 cells. When combined with flow cytometry on untreated marrow for calculation of the cloning efficiency, it gave very accurate determinations of residual T cell content of marrow. PMID- 2899867 TI - Retroviruses: new viral infections in man. PMID- 2899868 TI - Both presynaptic nicotinic-like and muscarinic-like autoreceptors regulate acetylcholine release at an identified neuro-neuronal synapse of Aplysia. AB - The possible involvement of cholinergic presynaptic receptors regulating evoked quantal acetylcholine (ACh) release was investigated at an identified cholinergic neuro-neuronal synapse in the buccal ganglion of Aplysia, using cholinergic agonists (carbachol, pilocarpine, oxotremorine) and/or antagonists (curare, atropine, hexamethonium). Bath applied carbachol or pilocarpine (10(-8) M to 10( 4) M) induced a decrease in the evoked quantal release of ACh. As the effects of carbachol were prevented by atropine (5.10(-6) M) and not by curare (10(-5) M), it was concluded that carbachol activated presynaptic muscarinic-like receptors implicated in a negative feed-back on ACh release. On the contrary, oxotremorine (up to 10(-4) M) induced a potentiation of ACh release which was suppressed by curare (4.10(-6) M) or hexamethonium (10(-5) M) but not by atropine (5.10(-6) M) pointing to the activation of presynaptic nicotinic-like receptors implicated in a positive feed-back on ACh release. Moreover, in the presence of curare, oxotremorine decreased ACh release: this suggested that oxotremorine also activated the presynaptic muscarinic-like receptors. These results revealed the conjoint presence, on the same terminal, of both muscarinic-like and nicotinic like autoreceptors. PMID- 2899869 TI - Effects of serotonin on electrical properties of Madin-Darby canine kidney cells. AB - The present study has been performed to test for the influence of serotonin on the potential difference across the cell membrane (PD) of Madin-Darby canine kidney (MDCK)-cells. Under control conditions PD averages -48.6 +/- 0.6 mV (n = 98). Increasing extracellular potassium concentration from 5.4 to 10 and 20 mmol/l depolarizes the cell membrane by +6.3 +/- 0.6 mV (n = 6) and +14.1 +/- 1.0 mV (n = 12), respectively. The cell membrane is transiently hyperpolarized to 67.8 +/- 0.8 mV (n = 63) by 1 mumol/l serotonin. In the presence of serotonin, increasing extracellular potassium concentration from 5.4 to 20 mmol/l depolarizes the cell membrane by +26.4 +/- 1.0 mV (n = 11). 1 mmol/l barium depolarizes the cell membrane by +15.7 +/- 1.3 mV (n = 17) and abolishes the effect of step increases of extracellular potassium concentration from 5.4 to 10 mmol/l. In the presence of barium, serotonin leads to a transient hyperpolarization by -26.3 +/- 1.0 mV (n = 16). During this transient hyperpolarization, the cell membrane is sensitive to extracellular potassium concentration despite the continued presence of barium. 10 mumol/l methysergide hyperpolarize the cell membrane by -7.2 +/- 2.0 mV (n = 6). In the presence of 10 mumol/l methysergide, the effect of serotonin is virtually abolished (+0.4 +/- 0.9 mV, n = 6). 1 mumol/l ketanserin, a 5-HT2 receptor blocking agent, ICS 205 930, a 5-HT3 receptor blocking agent, and phentolamine, an unspecific alpha receptor blocking agent, do not significantly modify the effect of serotonin. In the nominal absence of extracellular calcium, the effect of serotonin is markedly reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899871 TI - Cloning and nucleotide sequence of the gene encoding yeast ribosomal protein YS25. PMID- 2899872 TI - Sequence of the gene encoding the mitochondrial F1-ATPase alpha subunit from Nicotiana plumbaginifolia. PMID- 2899870 TI - A novel human cytochrome P450 gene (P450IIB): chromosomal localization and evidence for alternative splicing. AB - We have isolated from a single human liver cDNA library two clones which are highly homologous (78% over the coding region) to the major phenobarbital inducible P450 from rat (P450IIB1). This is the first direct demonstration of the presence of the P450IIB gene subfamily in humans. This subfamily is much less extensive than the rodent homologues, but does appear to contain at least two genes. Of the cDNA clones isolated one is apparently normally spliced, whereas the other lacks exon 8 and retains all or part of intron 5. Both clones contain transcribed Alu sequences. The human P450IIB gene has been located to chromosome 19q12----19q13.2 using a probe derived from intron 5, and is close to the CYP 2A locus encoding cytochrome P450IIA2. Restriction fragment length polymorphisms have been found with the enzymes BamHI and MspI which will enable linkage to be determined between these two loci. PMID- 2899873 TI - RFLPs revealed by cosmid 131 [HGM9 no. D17S78]. PMID- 2899874 TI - Cosmid 128 defines three RFLPs on chromosome 17q23-qter. [HGM9 no. D17S77]. PMID- 2899875 TI - A PstI RFLP for the human retinoic acid receptor in 17q21. PMID- 2899876 TI - Two EcoT14I RFLPs at the human renin (REN) gene locus. PMID- 2899877 TI - Isolation and mapping of a polymorphic DNA sequence (pCMM66) on chromosome 14 [D14S22]. PMID- 2899879 TI - Isolation and mapping of a polymorphic DNA sequence (pMCOC12) on chromosome 14 [D14S20]. PMID- 2899878 TI - Isolation and mapping of a polymorphic DNA sequence (pEFD85.7) on chromosome 15 [D15S37]. PMID- 2899880 TI - Isolation and mapping of a polymorphic DNA sequence (cMCOE32) on chromosome 2 [D2S53]. PMID- 2899881 TI - EcoT14I RFLP found at the human amyloid beta protein gene locus. PMID- 2899882 TI - Calf thymus DNA polymerase delta: purification, biochemical and functional properties of the enzyme after its separation from DNA polymerase alpha, a DNA dependent ATPase and proliferating cell nuclear antigen. AB - We have established a novel procedure to purify calf thymus DNA polymerase delta from cytoplasmic extracts. The enzyme has typical properties of DNA polymerase delta including a 3' - greater than 5' exonuclease activity and efficiently replicates natural occurring genomes such as primed single-stranded M13 DNA and single-stranded porcine circovirus DNA, this last one thanks to an associated or contaminating primase activity. A processivity of at least a thousand bases was evident and this in the apparent absence of proliferating cell nuclear antigen. The enzyme was purified through a procedure that allows the simultaneous isolation of DNA polymerase delta, DNA polymerase alpha-primase and a DNA dependent ATPase. All these enzymes coeluted from a phosphocellulose column. After chromatography on hydroxylapatite DNA polymerase delta separated from the coeluting DNA polymerase alpha and DNA dependent ATPase. Separation of the latter two was achieved on heparin-Sepharose. DNA polymerase delta was further purified by heparin-Sepharose and fast protein liquid chromatography. Purified DNA polymerase delta was resistant to the DNA polymerase alpha inhibitors BuPdGTP and BuAdATP and did not react with DNA polymerase alpha monoclonal and polyclonal antibodies. Based on this isolation protocol we can start to test biochemically the hypothesis whether DNA polymerase delta and DNA polymerase alpha might act coordinately at the replication fork as leading and lagging strand replicases, respectively. PMID- 2899883 TI - Mammalian cyclin/PCNA (DNA polymerase delta auxiliary protein) stimulates processive DNA synthesis by yeast DNA polymerase III. AB - Human cyclin/PCNA (proliferating cell nuclear antigen) is structurally, functionally, and immunologically homologous to the calf thymus auxiliary protein for DNA polymerase delta. This auxiliary protein has been investigated as a stimulatory factor for the nuclear DNA polymerases from S. cerevisiae. Calf cyclin/PCNA enhances by more than ten-fold the ability of DNA polymerase III to replicate templates with high template/primer ratios, e.g. poly(dA).oligo(dT) (40:1). The degree of stimulation increases with the template/primer ratio. At a high template/primer ratio, i.e. low primer density, cyclin/PCNA greatly increases processive DNA synthesis by DNA polymerase III. At low template/primer ratios (e.g. poly(dA).oligo(dT) (2.5:1), where addition of cyclin/PCNA only minimally increases the processivity of DNA polymerase III, a several-fold stimulation of total DNA synthesis is still observed. This indicates that cyclin/PCNA may also increase productive binding of DNA polymerase III to the template-primer and stabilize the template-primer-polymerase complex. The activity of yeast DNA polymerases I and II is not affected by addition of cyclin/PCNA. These results strengthen the hypothesis that yeast DNA polymerase III is functionally analogous to the mammalian DNA polymerase delta. PMID- 2899886 TI - Mosquito transmission of HIV remains unsupported. PMID- 2899885 TI - The phenomenon of analgesic tolerance in cancer pain management. PMID- 2899884 TI - The Drosophila engrailed protein is phosphorylated by a serine-specific protein kinase. AB - The engrailed gene is required during embryogenesis of Drosophila melanogaster for normal segmental development and for differentiation of posterior compartments. The protein encoded by the engrailed gene contains a homeodomain, has sequence specific DNA binding activity, and has been proposed as a transcriptional regulator. We show here that the engrailed protein, isolated from both cultured cells and embryos, has been modified by a serine-specific protein kinase. This is the first report that homeobox proteins are post-translationally modified. Phosphorylation of the engrailed protein may directly or allosterically modify its function, and offers the possibility that the engrailed protein becomes phosphorylated in response to extracellular, mitogenic or positional stimuli. PMID- 2899887 TI - [Presence of benzodiazepines in the serum of patients after accidents. Relation to alcoholism]. AB - In a study of 2.021 injured persons (accidents at home or at work, road accidents), qualitative assays of serum benzodiazepines by the EMIT method were positive in 9.6 per cent of the cases, including 3.2 per cent who had blood alcohol levels in excess of 0.10 g/l. Benzodiazepines were more frequently found in accidents at home and on roads than in accidents at work. These results raise the question of the role played by benzodiazepines as a possible risk factor of accidents, notably road accidents. PMID- 2899888 TI - [Remission of recurrent Cushing's disease with an analog of somatostatin]. PMID- 2899889 TI - Phosphorylation process induced by epidermal growth factor alters the oncogenic and cellular neu (NGL) gene products. AB - The rat neu oncogene encodes a cell surface glycoprotein, p185, that possesses tyrosine kinase activity. The p185 polypeptide exhibits structural similarity to the epidermal growth factor receptor (EGFR) at both the deduced amino acid and nucleic acid level. However, the neu oncogene and the gene encoding the EGFR have been shown to reside on distinct chromosomes. Comparative analysis of the sequences of the normal neu cDNA and of the neu cDNA from neuroblastomas has revealed a single point mutation leading to a valine-to-glutamic acid substitution in the transmembrane anchoring domain. This mutation converts the neu gene to a transforming gene in rodents. In humans, the gene is called ERBB2 (also NGL and HER2), and amplification and over-expression of its products have been detected in certain tumors. The rat embryonal fibroblast cell line (Rat-1) appears to express both EGFR and cellular p185 polypeptides. We have found that EGF stimulates the phosphorylation of p185 in these cells at tyrosine as well as serine and threonine residues in a specific and dose-dependent manner. This activity occurs even though radiolabeled EGF cannot bind to immunopurified p185. The EGF effect is apparently unique since platelet-derived growth factor, insulin, and transforming growth factor beta all fail to phosphorylate p185 at tyrosine. The EGF-induced effect requires interaction of the EGFR and its cognate ligand because cell lines that lack EGFR cannot be shown to phosphorylate p185, even when exposed to large amounts of EGF. Oncogenic rodent p185 and the human p185 homologue ERBB2 that is overexpressed in human breast tumor cells also can be shown to become phosphorylated on tyrosine residues by the action of EGF. Collectively, these data demonstrate that EGF mediates phosphorylation of p185 at tyrosine as well as serine/threonine through cellular kinases by a receptor specific mechanism. PMID- 2899890 TI - Increased tyrosine kinase activity associated with the protein encoded by the activated neu oncogene. AB - A single mutation altering the transmembrane domain of the receptor-like p185 protein encoded by the rat neu gene converts the normal neu gene into a potent oncogene. The biochemical consequences of this mutation were studied by examining phosphorylation of the normal and transforming p185 molecules in membrane preparations. Here we show that the transforming p185 is phosphorylated to a much higher extent in vitro than its normal counterpart. This preferential phosphorylation has the properties that would be expected of p185 autophosphorylation: it takes place on tyrosine and requires intact p185 kinase activity. The normal p185 protein does not demonstrate increased phosphorylation even when it coexists in a transformed cell with the transforming p185 protein. These data show that transforming p185 is specifically associated with an active tyrosine kinase activity and suggest that this activity is intrinsic to the transforming protein. Thus, the transmembrane domain of p185 appears to directly regulate its kinase activity. PMID- 2899891 TI - Insulin stimulates the dephosphorylation and activation of acetyl-CoA carboxylase. AB - The mechanism underlying the ability of insulin to acutely activate acetyl-CoA carboxylase [acetyl-CoA: carbon-dioxide ligase (ADP-forming), EC 6.4.1.2; AcCoA Case] has been examined in Fao Reuber hepatoma cells. Insulin promotes the rapid activation of AcCoACase, as measured in cell lysates, and this stimulation persists to the same degree after isolation of AcCoACase by avidin-Sepharose chromatography. The insulin-stimulated enzyme, as compared with control enzyme, exhibits an increase in both citrate-independent and -dependent activity and a decrease in the Ka for citrate. Direct examination of the phosphorylation state of isolated 32P-labeled AcCoACase after insulin exposure reveals a marked decrease in total enzyme phosphorylation coincident with activation. The dephosphorylation due to insulin appears to be restricted to the phosphorylation sites previously shown to regulate AcCoACase activity. All of these effects of insulin are mimicked by a low molecular weight autocrine factor, tentatively identified as an oligosaccharide, present in conditioned medium of hepatoma cells. These data suggest that insulin may activate AcCoACase by inhibiting the activity of protein kinase(s) or stimulating the activity of protein phosphatase(s) that control the phosphorylation state of the enzyme. PMID- 2899892 TI - Interleukin 1 prevents loss of corticotropic responsiveness to beta-adrenergic stimulation in vitro. AB - Corticotropin (ACTH) secretion by the anterior pituitary is stimulated by catecholamines in vivo and in vitro. The nature of the response in vivo is controversial but appears to be mediated by beta-adrenergic receptors, whereas the response is dependent on alpha-adrenergic receptors in cultured anterior pituitary cells. In the present studies, by using a superfusion technique, we demonstrate that catecholamine stimulation of ACTH release from rat anterior pituitaries changes with time from a predominantly beta-adrenergic-mediated event to a predominantly alpha-adrenergic-mediated event. From 0 to 2 hr after initiating the superfusion, release of ACTH from anterior pituitary glands is stimulated up to 2.4-fold by the beta-adrenergic agonist l-isoproterenol. However, the ACTH secretory response to the alpha-adrenergic agonist l phenylephrine is less than or equal to 5% of that to l-isoproterenol during the same time period. Beginning 2 hr after the start of the superfusion, the responsiveness to the beta-adrenergic agonist declines, and the response to the alpha-adrenergic agonist increases until, 10 hr after removal, greater than 95% of the catecholamine-inducible ACTH release is mediated by an alpha-adrenergic pathway. The addition of interleukin 1 alone to the medium from the beginning of the superfusion does not modify basal ACTH secretion rates and does not affect the acquisition of the response to phenylephrine. However, the presence of interleukin 1 does allow the maintenance of the full ACTH secretory response to isoproterenol. This effect of interleukin 1 is reversed by an interleukin 1 antagonist. These observations suggest an additional way in which immune regulators might interact with the hypothalamic-pituitary-adrenal axis. PMID- 2899895 TI - Evidence for the connections between a clutch cell and a corticotectal neuron in area 17 of the cat visual cortex. AB - Evidence is presented for the synaptic connectivity between a physiologically characterized and intracellularly filled GABAergic interneuron and a corticotectal pyramidal neuron in area 17 of the cat visual cortex. The interneuron was located in layer 4 and had the morphological characteristics of a clutch cell. The physiological data demonstrated that the clutch cell received direct X-type innervation from the dorsal lateral geniculate nucleus. These results indicate that a GABAergic neuron is directly involved during the first cortical stages of geniculocorticotectal interactions. Furthermore, the proximal location of the clutch-cell inputs to the labelled dendrite suggests a strategic siting of intracortical feedforward inhibition. PMID- 2899894 TI - Radioimmunoassay for octapeptide analogs of somatostatin: measurement of serum levels after administration of long-acting microcapsule formulations. AB - The development of a long-acting delivery system for D-Phe-Cys-Tyr-D-Trp-Lys-Val Cys-Trp-NH2 (RC-160), an octapeptide analog of somatostatin, required the establishment of a method for determining the concentration of this analog in serum during treatment. A sensitive and specific radioimmunoassay (RIA) for RC 160 was developed and used for following the rate of liberation of this peptide from microcapsules of poly(DL-lactide-coglycolide). Antibodies were generated in a rabbit against RC-160 conjugated to bovine serum albumin with glutaraldehyde. At an antiserum dilution of 1:100,000, the antibodies bound approximately 25% of added radiolabeled RC-160. Somatostatin octapeptide analogs that had a disulfide bridge showed crossreactivity with the antiserum, but analogs without the disulfide bridge and other peptides tested did not crossreact. The minimum detectable dose of RC-160 was 10 pg. Intra- and interassay coefficients of variation ranged from 9.1% to 12.8% and from 14% to 30%, respectively. The RIA was suitable for direct determination of RC-160 in serum. Eleven prototype batches of microcapsules were tested in rats, and the rate of release of the analog from the microcapsules was followed. An improved batch of microcapsules made from RC-160 pamoate maintained high serum levels of RC-160 for more than 30 days after intramuscular injection. The RIA should be of value for monitoring levels of this analog in serum during long-term therapy. PMID- 2899896 TI - Receptor kinetics pertaining to blockade of nerve-released transmitter at synapses. AB - The question is raised as to whether competitive inhibitors should block responses of tissue to nerve-released neurotransmitter to the same extent as they block equivalent responses to exogenous agonist. From a simple dynamic model of synaptic events, which takes into account non-constancy of transmitter concentration in space and time, it is deduced that equal blockade of responses to nerve-released and exogenous transmitter substance will occur if: (i) there are locally many more receptor molecules than transmitter molecules; (ii) the active agonist-receptor complex, AnR, has n = 1; and (iii) tissue response is insensitive to spatial or temporal inhomogeneity of AR. In such a case there will also be equal sensitivity of responses to other modes of inhibition: irreversible competitive, uncompetitive, and non-competitive. Equal blockade of responses to equi-effective endogenous and exogenous agonist will also occur if nerve stimulation gives rise to a steady uniform concentration of agonist, so that equilibrium kinetics are applicable. When n greater than 1 and/or when tissue responses reflect local peak AnR, response to nerve-released transmitter will be relatively insensitive to receptor blockade by a competitive inhibitor. The same is true for irreversible competitive blockade or for modulation of receptor density. However, an uncompetitive inhibitor (e.g. a 'channel blocker') may be more effective against nerve-released agonist than against exogenous agonist. PMID- 2899893 TI - Structure and expression of Hox-2.2, a murine homeobox-containing gene. AB - The Hox-2.2 gene is one of a cluster of homeobox-containing genes on mouse chromosome 11. A cDNA clone containing the Hox-2.2 homeobox has been isolated from an adult spinal cord library. Our analysis of the Hox-2.2 cDNA and genomic clones indicates that there are at least two oxons and one intron. The largest open reading frame includes the homeobox and codes for a 224 amino acid protein of molecular weight 25,312. Comparisons of the predicted Hox-2.2 protein with other homeodomain-containing proteins revealed four regions of sequence similiarity: an N-terminal octapeptide, a hexapeptide upstream of the homeodomain, the homeodomain, and a glutamic acid-rich region at the C terminus. Possible functions of these regions are discussed. The Hox-2.2 gene is expressed in 13.5-day embryos in the developing hindbrain and spinal cord. The expression patterns of Hox-2.2 and Hox-2.1 in 13.5-day embryos are compared. PMID- 2899897 TI - Biochemical hypotheses on antidepressant drugs: a guide for clinicians or a toy for pharmacologists? AB - The development of knowledge about the mechanism of action of tricyclic and the so-called 'atypical' antidepressants (AD) is reviewed. The discovery of clinically active antidepressants with little or no effect on noradrenaline or serotonin uptake has disproved the widely accepted concept that inhibition of monoamine uptake is a prerequisite for antidepressant activity. Another serious objection to this hypothesis is that blockade of monoamine uptake occurs in a matter of minutes after administration while 2-3 weeks of repeated treatment are necessary for the clinical AD effect. Nevertheless, the effect of repeated treatment with AD is compatible with the hypothesis that changes in central monoamine transmission are involved in the clinical activity of these drugs. Major changes in monoamine function after repeated treatment with AD include: desensitization and reduced density of noradrenaline receptors coupled to the adenylcyclase system, opposite changes in the sensitivity of alpha 1 (increased) and alpha 2-adrenoreceptors (decreased), down regulation of serotonin2 receptors and complex changes in the behavioural and electrophysiological responsiveness to serotonin agonists, subsensitivity of presynaptic dopamine receptors and enhanced activity of the mesolimbic dopamine system, decreased and increased density of GABA-A and GABA-B receptors respectively and down regulation of [3H]benzodiazepine binding. It remains to be clarified whether some of these changes have larger roles than others or whether they all contribute to the AD activity. An important role of dopamine in the activity of AD drugs is suggested by findings in the forced swimming test, whereas both catecholamines seem to be involved in the attenuation of escape deficit provoked by inescapable shock (learned helplessness).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899899 TI - [Regulation of Thy-1 gene expression]. PMID- 2899898 TI - Cognitive impairment in long-term benzodiazepine users. AB - In view of the very extensive and often prolonged use of benzodiazepines in therapeutic practice, this study was designed to investigate whether or not cognitive ability is impaired in long-term benzodiazepine users, and to determine the nature and extent of any deficit. Fifty patients currently taking benzodiazepines for at least one year, thirty-four who had stopped taking benzodiazepines, and a matched control group of subjects who had never taken benzodiazepines or who had taken benzodiazepines in the past for less than one year were administered a battery of neuropsychological tests designed to measure a wide range of cognitive functions. It was found that patients taking high doses of benzodiazepines for long periods of time perform poorly on tasks involving visual-spatial ability and sustained attention. This is consistent with deficits in posterior cortical cognitive function. PMID- 2899900 TI - [Pregnancy and asthma]. AB - One in a hundred pregnant females has asthma. Pregnancy may change the course of the asthma and inversely foetal and obstetric prognosis may be affected by the illness and by the potentially deleterious effect of treatment. The maternal physiological changes which occur during pregnancy throw little light on the variations in asthma during pregnancy. Clinical studies in the literature suggest that the quality of follow-up and treatment in patients allows for a satisfactory outcome in pregnancy and that it is an important prognostic factor. Overall, taking account of the pregnancy and confinement the therapeutic approach of the thoracic physician differs little from that in management outside pregnancy. The first objective is to relieve the bronchial obstruction. Broncho-dilator therapy with beta-agonist and by theophylline remains usable in most cases. The side effects of steroid therapy ought to be balanced against the advantages, in order to maintain a normal physiological state. Immunotherapy, and antibiotics should be adapted appropriately for the pregnancy and for their respective contra indications. Finally, the prevention of atopy should be envisaged. PMID- 2899902 TI - [A new therapy for acromegaly]. PMID- 2899901 TI - [TSH-secreting pituitary adenomas]. PMID- 2899903 TI - [Reverse genetics and prenatal diagnosis]. AB - "Reverse" genetics is a research process consisting in finding the gene of a disease, then in "descending" toward the final product that it codes. This reasoning is the reverse of the one normally used which "ascends from the protein to the gene" and can be applied to the discovery of the pathogenic mechanism of a disease. There are numerous spin-offs of this new type of approach for prenatal diagnosis (PND). Thus, the discovery of polymorphic tracers surrounding the gene enables an indirect PND in informative families. Reliability is great if we have many probes at our disposal. Then, discovery of the gene itself permits a direct PND with the use of intragenic probes and synthetic oligonucleotides. PMID- 2899904 TI - [Somatostatinoma of the pancreas]. PMID- 2899905 TI - Monoclonal autoantibodies specific for kidney proximal tubular brush border from mice with experimentally induced chronic graft-versus-host disease. AB - Nine hybridomas producing monoclonal autoantibodies specific for kidney proximal tubular brush border were found in 600 hybridomas derived from (C57BL/6J X DBA/2)F1 mice injected with DBA/2 T cells. None of the 1100 hybridomas derived from nonautoimmune (C57BL/6J X DBA/2)F1 mice produced antibodies with a similar specificity. Four of these nine monoclonal antibodies were characterized further. They did not bind to cryosections of liver, lung, stomach, or intestine. Three bound to kidney proximal tubular brush border of mouse, cattle, sheep, pigs, rabbits, rats, and humans, whereas the fourth was specific only for murine brush border. All four precipitated from mouse kidney microvilli, a protein with an apparent molecular weight of 160,000 under reducing as well as nonreducing conditions. Removal of asparagine-linked carbohydrate with EndoF reduced the molecular weight of the 160,000 protein by about 20,000. One of the three multi species-specific antibodies bound to pig kidney aminopeptidase, a glycosylated enzyme located on the microvilli of kidney proximal tubular brush border. Three antibodies have a heavy-chain variable region encoded by VH genes of the J558 family, whereas the heavy-chain variable region of the fourth is encoded by a VH gene of the 7183 family. Attempts to passively transfer immune complex glomerulonephritis to normal mice by injection of the purified monoclonal antibodies or by growth of the corresponding hybridoma cells in mice have so far been unsuccessful. However, antibodies recognizing the 160,000 molecule are present in the serum of mice with chronic graft-versus-host disease and can be eluted from kidneys with immune complex glomerulonephritis. PMID- 2899906 TI - Efficacy and safety of once daily versus intermittent dosing of tobramycin in rabbits with acute pyelonephritis. AB - Unilateral pyelonephritis was induced in 50 rabbits by injecting Escherichia coli (minimum inhibitory concentration of tobramycin 0.25 mg/l) into the left kidney and by obstructing the ureter temporarily. Tobramycin treatment (daily dose 10 mg/kg) was started 4 days after surgery, either in a single daily dose or in 3 divided doses at 8 h intervals, for 2, 3, 5, 7 or 10 days. Comparison of bacteriology, renal morphology, and renal functions (BUN, serum creatinine, alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, cathepsin B, sphingomyelinase) suggests better efficacy and renal tolerance of the single daily dose regimen in the treatment of experimental acute pyelonephritis. PMID- 2899907 TI - Management of postoperative pain after abdominal surgery. PMID- 2899908 TI - HIV-1-infected T cells show a selective signaling defect after perturbation of CD3/antigen receptor. AB - The binding of antigen or monoclonal antibody to the T cell receptor for antigen or the closely associated CD3 complex causes increases in the concentration of intracellular ionized calcium and subsequent cell proliferation. By measuring second messenger production in primary cultures of human immunodeficiency virus (HIV-1)--infected T cells stimulated with monoclonal antibodies specific for either CD3 or CD2, a specific impairment of membrane signaling was revealed. The HIV-1--infected T cells were unable to mobilize Ca2+ after stimulation with anti CD3, whereas CD2-induced calcium mobilization remained intact. Furthermore, the HIV-1--infected cells proliferated poorly after CD3 stimulation, although the cells retained normal DNA synthesis in response to interleukin-2 stimulation. These results show that the signals initiated by CD2 and CD3 can be regulated independently within the same T cell; uncoupling of signal transduction after antigen-specific stimulation provides a biochemical mechanism to explain, in part, the profound immunodeficiency of patients with HIV-1 infection. PMID- 2899910 TI - [Corrective osteotomies of the foot in post-traumatic deformities]. PMID- 2899911 TI - [Antacids, histamine H2 receptor antagonists]. PMID- 2899909 TI - Quinoxalinediones: potent competitive non-NMDA glutamate receptor antagonists. AB - The N-methyl-D-aspartate (NMDA)-subtype of glutamate receptors has been well described as a result of the early appearance of NMDA antagonists, but no potent antagonist for the "non-NMDA" glutamate receptors has been available. Quinoxalinediones have now been found to be potent and competitive antagonists at non-NMDA glutamate receptors. These compounds will be useful in the determination of the structure-activity relations of quisqualate and kainate receptors and the role of such receptors in synaptic transmission in the mammalian brain. PMID- 2899912 TI - Characterization, evolutionary relationships, and chromosome location of processed mouse HPRT pseudogene. AB - Studies on a cell line with amplified copies of the mouse hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene and HPRT gene transfer experiments revealed the existence of a nonfunctional HPRT-related sequence in the mouse genome. This sequence was isolated and found to be a processed HPRT pseudogene. With the exception of a small internal deletion, the pseudogene is believed to comprise a complete reverse transcript of HPRT mRNA, although the 3' end of the pseudogene was lost in the cloning process. A probe from a region flanking the mouse pseudogene was used to investigate the evolutionary relationships of mammalian HPRT pseudogenes. The pseudogenes in mouse and Chinese hamster appear to have a common origin, but no homology to any of the four known human HPRT pseudogenes was detected. A pseudogene-linked restriction fragment length polymorphism was used to map the pseudogene to the distal end of mouse chromosome 17. PMID- 2899913 TI - Rapid reversal of life-threatening hypoglycaemia with a somatostatin analogue (octreotide). A case report. AB - A patient with life-threatening hypoglycaemia caused by metastatic malignant insulinoma is described. Treatment with octreotide (SMS 201-995, Sandostatin; Sandoz) resulted in immediate sustained improvement of the hypoglycaemia despite persistent high levels of insulin. The possible mechanisms of action, other indications and contraindications of octreotide are discussed. PMID- 2899914 TI - Discrimination between alpha 1- and alpha 2-adrenergic receptors in the isolated perfused ileum. AB - Adrenergic control over intestinal homeostasis has been associated with changes in intestinal vascular resistance, motility, and transport. With the use of selective alpha-adrenergic agents, this study was designed to discriminate between the vascular and transport effects. Rabbit 20 cm ileal segments (n = 31) were vascularly perfused at a rate of 1.5 ml/min by means of a modified Krebs solution containing 15% to 20% red cells. The intestinal lumen was perfused with an isotonic solution containing carbon 14-polyethylene glycol as a nonabsorbable marker. Net fluxes of water and electrolytes were calculated during 20-minute basal, experimental, and recovery periods. Norepinephrine (mixed alpha 1- and alpha 2-agonist) significantly increased intestinal absorption and vascular resistance. Phenylephrine (alpha 1-agonist) significantly increased vascular resistance without altering transport. Clonidine (alpha 2-agonist) stimulated intestinal absorption without changing vascular perfusion pressure. Yohimbine (alpha 2-antagonist) prevented norepinephrine-induced absorption but had no effect on norepinephrine-induced increases in perfusion pressure. In this isolated perfused whole gut model, alpha 1-adrenergic stimulation was responsible for increases in vascular resistance, and alpha 2-adrenergic stimulation was responsible for increases in the absorption of water and electrolytes. The ability to discriminate between alpha 1- and alpha 2-effects has potential therapeutic implications in patients with malabsorption and diarrhea. PMID- 2899915 TI - Influence of total nitrogen, asparagine, and glutamine on MCA tumor growth in the Fischer 344 rat. AB - Previous studies from this laboratory have demonstrated that growth of the methylcholanthrene (MCA) sarcoma is dependent on total nitrogen substrate availability in vivo and on the specific amino acids asparagine and glutamine in vitro. This experiment determines whether these two phenomena can be used to selectively depress tumor growth and maintain host carcass. Sixty-two rats were inoculated with sarcoma and were infused for 10 days with isocaloric (60 kcal/day) TPN solutions at 100%, 16%, 10%, and 5% of normal nitrogen levels, either with (W) or isonitrogenously without (WO) the amino acids asparagine, glutamine, aspartic acid, and glutamic acid. W solutions contained 33% of these amino acids. Mean weights of 100 W tumors were significantly greater (p = 0.002) than all other groups. Total body weights minus tumor weights were similar in W versus WO animals at each rate of nitrogen infusion. Mean venous plasma concentrations of asparagine, aspartic acid, glutamine, and glutamic acid were similar in all eight groups. These data indicate that the same degree of tumor depression produced by nitrogen deprivation can also be produced by removal of asparagine, glutamine, and their precursors from nutrient solutions without adverse effects on carcass mass. The mechanisms involved are not readily explained by analysis of venous plasma amino acid concentrations. PMID- 2899916 TI - Control of gastrin release in cultured gastrinoma-derived G cells. AB - Functional gastrin-containing tumor cells (GT cells) have been maintained in short-term culture on microporous membranes, and their response to selected agents has been determined. After dispersion of gastrinoma by collagenase-DNAase digestion coupled with mechanical disruption, dispersed cells were depleted in stromal material by selective attachment to a plastic substrate, then cultured for 72 hours on porous cellulose membranes. Cultures contained 68 +/- 5% GT cells with a viability of 92 +/- 2%. Secretin stimulated the rate of gastrin release from cultured GT cells in both a time- and a dose-dependent fashion. To examine the possible involvement of adenylate cyclase- and protein kinase C-mediated mechanisms in regulating gastrin release from the neoplastic GT cells, we evaluated the effects of 8-bromoadenosine 3':5'-cyclic monophosphate (8-BrcAMP; 10(-4) - 10(-2) mol/L), the diterpene forskolin (10(-5) mol/L), 12-0 tetradencanoylphorobol 13-acetate (TPA; 10(-8) - 10(-6) mol/L), and 4 alpha phorbol 12,13-didecanoate (4 alpha PDD; 10(-8) - 10(-6) mol/L) on gastrin release. Among all compounds tested, 8-BrcAMP (10(-2) mol/L) was the most potent, stimulating the rate of gastrin release 263% above basal. Both 8-BrcAMP and TPA stimulated gastrin release in a dose-dependent fashion. The biologically inactive phorbol ester, 4 alpha PDD, was without effect at all concentrations. Somatostatin (10(-8) - 10(-6) mol/L) inhibited 8-BrcAMP-stimulated gastrin release in a dose-dependent fashion to a maximum of 75%. PMID- 2899917 TI - Regulatory decision making and the need for and the use of exposure data on pesticides determined to be teratogenic in test animals. AB - Major efforts have been made in the development of a system that takes the reviewer step-by-step by the use of the developmental toxicity and exposure assessment data to a recommended risk assessment and risk management position. Thereupon a set of regulatory decisions can be arrived at that are backed up by sound scientific analysis. Examples of pesticides that have been found to be teratogenic in animal testing are provided to demonstrate the process of use of exposure data in making risk assessment and management decisions. PMID- 2899918 TI - Effects of N-acetylcysteine on fetal development and on phenytoin teratogenicity in mice. AB - The teratogenicity of phenytoin may result from its enzymatic bioactivation to a reactive intermediate, which interacts irreversibly with fetal tissues. Since glutathione (GSH) is involved in the detoxification of many reactive intermediates, N-acetylcysteine (NAC), a glutathione precursor, was evaluated for its effects on murine fetal development and phenytoin teratogenicity. NAC, 100 to 275 mg/kg, was given intraperitoneally (ip) or per os (po), or as 266 to 410 mg/kg in the drinking water, at various times before or after phenytoin, 65 to 75 mg/kg ip, on gestational days 12 and 13. Dams were killed on gestational day 19, fetal resorptions were noted, and fetuses were examined for anomalies. Significant reductions in phenytoin-induced fetal weight loss and cleft palates were observed when NAC was given by gavage 6 hours after phenytoin or in the drinking water with the lower dose of phenytoin. NAC administered in the drinking water also reduced the incidence of resorptions produced by the higher dose of phenytoin and enhanced postpartum survival in fetuses exposed to 65 or 75 mg/kg phenytoin (P less than .05). Conversely, the incidence of resorptions increased when NAC was given by gavage at other times before or after phenytoin, by single or repetitive ip injections, or in high concentrations in the drinking water (P less than .05). When given with the higher dose of phenytoin, NAC administered via the drinking water significantly increased the incidence of phenytoin-induced cleft palates and fetal weight loss (P less than .05). Similar results were obtained with a single ip injection of NAC and a lower dose of phenytoin. Thus, when given orally, NAC can partially reduce phenytoin teratogenicity and embryopathy. However, altering the route of NAC administration, or increasing the dose of phenytoin and/or NAC, enhanced phenytoin embryotoxicity, and NAC alone at higher doses had embryopathic effects. PMID- 2899919 TI - Effect of smokeless tobacco on the development of the CD-1 mouse fetus. AB - The objective of this study was to examine the effect of smokeless tobacco (ST) on the development of the CD-1 mouse fetus. ST was administered continuously via Alzet osmotic minipumps during the critical gestational days 7-14 and 6-13. Two ST dosages were administered, 3.2 mg/ml (Dosage I) and 6.4 mg/ml (Dosage II), which yielded plasma nicotine levels within the range comparable to those of an average ST user or smoker (36.0 ng/ml). Plasma nicotine levels were maintained in the range of 29.4 +/- 4.8 ng/ml to 44.3 +/- 16.0 ng/ml for the Dosage I group of dams, and in the range of 34.6 +/- 10.9 ng/ml of 75.5 +/- 19.9 ng/ml for the Dosage II group of dams. The main effect on the fetus was weight reduction, with Dosage I producing a tendency toward weight reduction (p = .08). Dosage II produced a significant 8.6% weight reduction from normal (p less than .0001) and an increase in fetal deaths (p less than .03). Dosage I produced an increase in the incidence of hemorrhages and supernumerary ribs, and a significant delay (p less than .05) in ossification of the supraoccipital bone, the sacrococcygeal vertebrae, and the bones of the forefoot and hindfoot. There were no significant differences between placental weights. Weights of dams were significantly reduced only at the higher ST exposure levels. We conclude that at plasma nicotine levels comparable to those of an average ST user, ST produces weight reduction, delayed ossification, and increase in hemorrhages and fetolethality in the CD-1 mouse fetus. PMID- 2899920 TI - Stage-related induction of chromosomal aberrations and SCE in mouse embryos treated transplacentally during organogenesis with MMC and DMBA. AB - During organogenesis, mouse embryos were treated transplacentally with MMC and DMBA. The clastogenic and SCE-inducing effects of MMC and the clastogenic effects of DMBA were analyzed in metaphases from whole embryo suspensions. Positive effects were observed on all the days of pregnancy on which the embryos were analyzed, i.e., on days 10, 11, 12, and 13. Whereas the MMC-induced SCE frequencies did not change significantly during the tested period, the clastogenic effects of MMC and DMBA varied drastically. Extremely high aberration rates were observed in embryos on day 11; on the other days the aberration rates were much lower. Factors that might have given rise to these stage-related effects are discussed. PMID- 2899921 TI - Tissue injury and proliferative response induced in rat kidney by cis diamminedichloroplatinum (II). AB - Cis-diamminedichloroplatinum (II) (cisplatin), an inorganic platinum salt used in cancer chemotherapy, is characterized by a renal toxicity recognized both in experimental animals and in patients treated with the compound. The purpose of the present study was to explore by both light and electron microscopy the morphological alterations induced in the rat kidney by cisplatin administration and, in particular, to analyse the tissue repair reaction following nephrotoxic injury. Experimental animals (four rats per group) were treated i.p. with 2, 4 or 8 mg/kg cisplatin administered in four consecutive daily injections. The rats were sacrificed 4 days after the last injection. In addition, the persistence of renal lesions and the duration of the repair reaction were determined in rats given 8 mg/kg cisplatin and killed 4, 7, 14 or 21 days after the last injection. The cell proliferation associated with tissue repair was estimated both quantitatively (rate of DNA synthesis) and qualitatively (histoautoradiography and electron microscopy examination) 1 h after in vivo exposure to [3H] thymidine. Renal tissue alterations and the repair reaction were minimal after the administration of 2 or 4 mg/kg cisplatin. In contrast, 8 mg/kg cisplatin caused a spectrum of morphological abnormalities affecting proximal, distal and collecting tubules, and ranging from sublethal cell alterations to tubular necrosis and cystic dilatation. The latter degenerative change primarily involved the straight portion of proximal tubules and seemed to develop over the weeks following cisplatin administration. Concomitantly with the tissue lesions, a burst of cell proliferation, associated with stimulation of DNA synthesis, was apparent in the renal cortex and outer medulla. Whereas a very high incidence of S-phase cells was encountered in seemingly undifferentiated tubules, they also appeared in differentiated proximal, distal and collecting tubules, but were infrequent in cystic tubules. Proliferation of fibroblasts was also stimulated in the renal interstitium. The proliferative response persisted for the whole duration of the experiment, indicating incomplete tissue repair. The long-lasting tubular injury and the slowness of repair are consistent with the chronic renal dysfunction (polyuria and hypomagnesemia) that cisplatin is known to induce in both man and experimental animals. PMID- 2899922 TI - Hodgkin cells in freeze-fracture replicas. AB - Lymph nodes from six patients with Hodgkin's disease (three with the nodular sclerosing subtype, one with mixed cellularity and two with the lymphocyte predominant subtype) were analysed by electron microscopy in freeze-fracture replicas and thin sections. Two main variants of Hodgkin cell could be identified in the nodular sclerosing and mixed cellularity subtypes. (1) Hodgkin cells with wide cytoplasm and short, smooth- and rough-surfaced tubular profiles of endoplasmic reticulum (ER) unevenly scattered in the cytoplasm. (2) Hodgkin cells with well developed rough ER. In freeze-fracture replicas the ER was seen to consist of both short and long tubules, some of the latter forming anastomoses with each other. Both cell types possessed branching cytoplasmic processes. A P face rich in intramembrane particles (IMP) and an E-face with few IMP were common to both Hodgkin cell types. These cells do not, therefore, possess the membrane features characteristic of interdigitating reticulum cells, thus refuting the previously held belief that Hodgkin cells, in particular lacunar cells, are related to interdigitating reticulum cells. The cytoplasmic structures and membrane characteristics of Hodgkin cells in the lymphocyte-predominant subtype (L & H cells) are similar to other Hodgkin cells in that they may show a high content of rER, and the P-face of these cells contains more IMP than the E-face. Both characteristics support the theory put forward in the literature (based on immunohistochemical findings) that these are lymphoid cells (immunoblasts or immature plasma cells). PMID- 2899923 TI - Structure and motility of primary cilia in the follicular epithelium of the human thyroid. AB - In order to clarify contradictory reports concerning ciliary structure and function, follicular epithelium from macroscopically normal portions of 37 surgical specimens of human thyroid were processed for video-microscopy and/or transmission electron microscopy. The cilia of living cells were immotile. In transverse sections the cilia revealed a 9 + 0 pattern at the base of the shaft, whereas towards the distal end the number of microtubular doublets diminished. Dynein arms, radial spokes and central microtubules were absent. The immotility and structure of these primary cilia implies that their function is not related to motility. The phylogenetic and ontogenetic development of the thyroid suggests that tumor cells of follicular origin displaying abnormal secondary cilia may represent a pathological variant of differentiation. PMID- 2899924 TI - Effects of all-trans retinol and cigarette smoke condensate on hamster tracheal epithelium in organ culture. I. A cell proliferation study. AB - The effects of cigarette smoke condensate (CSC) and all-trans retinol on the cell proliferative activity of vitamin A-deprived hamster tracheal epithelium have been studied in vitamin A-deficient, serum-free, hormone-supplemented medium in organ culture. In the absence of retinol, CSC induced a dose-dependent increase in labeling index (LI) during 12 days of culture. The basal cells were more sensitive to CSC exposure than non-basal cells during the first 6 to 8 culture days. However, in squamous metaplastic foci developing after culture day 6, both basal and non-basal cells in the mid-part of the epithelium were labeled. Physiological concentrations of all-trans retinol stimulated the non-basal LI and inhibited the basal cell LI. Compared with dimethylsulfoxide (DMSO), all retinol concentrations used in the present study inhibited the basal cell LI at each time point examined (4-12 days culture). Exposure of tracheal rings to retinol, either before or after exposure to CSC, or simultaneous exposure to retinol and CSC, clearly decreased the CSC-induced basal cell proliferative activity depending on the retinol concentration used. It is concluded from the present study that squamous metaplasia induced by vitamin A-deficiency or by CSC originates mainly from basal cells and that for the maintenance of these lesions, both basal and non-basal cells play a role. Furthermore, all-trans retinol inhibited CSC-induced basal cell proliferation. PMID- 2899925 TI - Effects of all-trans retinol and cigarette smoke condensate on hamster tracheal epithelium in organ culture. II. A histomorphological study. AB - The effects of all-trans retinol and cigarette smoke condensate (CSC) on tissue morphology and cellular differentiation were investigated in vitamin A-deprived tracheal epithelium cultured in vitamin A-and serum-free hormone-supplemented medium. Physiological retinol concentrations prevented the development of hyperplasia and squamous metaplasia with or without keratinization, and induced differentiation to mucous cells. Squamous metaplastic foci with keratinization were observed during 12 days of culture with low retinol concentrations and with dimethylsulfoxide (DMSO) which was accompanied by an increased number of basal and indeterminate cells. CSC induced a dose-related hyperplasia and irregularly shaped foci of squamous metaplasia with atypical epithelial proliferation. In non metaplastic epithelium, CSC exposure increased the number of ciliated cells. Hyperplasia and squamous metaplasia were inhibited if the tracheal rings were first treated with retinol followed by CSC exposure, or if the tracheas were simultaneously treated with retinol and CSC. CSC-exposure prior to retinol treatment induced similar histomorphological alterations as CSC alone. PMID- 2899926 TI - [The resolution of the 3d All-Union congress of specialists in physical therapy and sports medicine]. PMID- 2899927 TI - [Comparison of guanylate cyclase activity of the heart and thrombocytes in normal states and in experimental allergic myocarditis]. AB - Activity of soluble forms of guanylate cyclase from rabbit heart and thrombocytes was studied under conditions of normal state and in dynamics of heart allergic impairment: at the step preceding the impairment (step of sensitization), at the acute period (I-st day of the allergy) and at the step of reparation (14 day of the disease). The enzymatic activity was found to be 15-20-fold higher in thrombocytes as compared with that of heart muscle. Two-fold activation of the thrombocyte guanylate cyclase was detected at the step of sensitization; at the acute period the enzyme activity was distinctly decreased (below the values of normal state) an then normalized to the step of reparation. The similar but less distinct trend was observed in alterations of activity of myocardial guanylate cyclase. The data obtained suggest the conformity of the enzymatic properties in myocardium and thrombocytes under conditions of normal and pathological states. PMID- 2899929 TI - [Serum amine oxidases and gamma-glutamyl transpeptidase activity in burns]. AB - Activities of amine oxidases (benzylamine, 4-nitrobenzylamine, 4-dimethylamine methylbenzylamine used as substrates) and of gamma-glutamyl transpeptidase were studied in blood serum of 72 patients with thermic burns of various intensity and degree. Severity of the disease correlated with the rate of amine oxidases activity alteration. Distinct and long-term decrease in oxidation of benzylamine as well as simultaneous stimulation of 4-dimethylamine methylbenzylamine oxidation were observed in severe forms of the burns disease, thus suggesting the increase in diamine oxidase activity. This phenomenon proved to be an unfavourable prognostic indication of the disease. Alterations in activity of gamma-glutamyl transpeptidase corresponded to severity of the burns disease. Estimation of the enzymatic activity might be used in evaluation of the impairments severity as well as in prognosis of burns disease development. PMID- 2899928 TI - [Serum amine oxidase activity in children with mental deficiency]. AB - Correlation between a degree of mental deficiency and an activity of amine oxidase in blood serum as well as therapeutic efficiency of encephabole were found in children with mental deficiency of various genesis. Nootropile decreased the blood serum amine oxidase activity in the patients as well as the drug lowered the monoamine oxidase activity in brain mitochondria of young rats with antenatal hypoxia. PMID- 2899930 TI - [Use of signopam in the complex treatment of patients with mental disorders]. PMID- 2899932 TI - The pharmacokinetics and metabolism of idazoxan in the rat. AB - 1. [2'-14C]Idazoxan was rapidly and completely absorbed after its oral administration to rats. 2. After administration of either [2'-14C] or [6,7 3H]idazoxan, radioactivity was taken up by a wide range of tissues and became localized, especially in the organs of metabolism and excretion. Quantitative distribution patterns were route-dependent such that oral dosing resulted in lower radioactivity concentrations in all tissues apart from liver. 3. Clearance of idazoxan (94-144 ml/min per kg) was due mostly to metabolism and was independent of dose. Oral bioavailability in male rats at low oral doses of idazoxan (10 mg/kg) was about 1%, but increased with increasing dose to 23% at 100 mg/kg. Oral bioavailability in female rats was considerably higher than in male rats, at all doses studied. Brain idazoxan levels were in equilibrium with those in plasma, but ten-fold higher. 4. Elimination of radioactivity after administration of 14C-idazoxan was via the urine and the faeces (about 75% and 20% of dose respectively) and occurred essentially in the 24 h period immediately after dosing. By 96 h after dosing, elimination was virtually complete, with less than 0.5% dose remaining in the carcasses. 5. Biotransformation was by hydroxylation at positions 6 and 7 to form phenolic metabolites, which were excreted as glucuronide and sulphate metabolites in urine, but unconjugated in faeces. Other minor metabolic routes were 5-hydroxylation or oxidative degradation of the imidazoline ring, but these pathways were of quantitatively minor importance in the rat. PMID- 2899931 TI - Differential inhibition of human liver phenacetin O-deethylation by histamine and four histamine H2-receptor antagonists. AB - 1. The effects of histamine and four histamine H-2 receptor antagonists on phenacetin O-deethylation by microsomal preparations of four human livers was quantified by a radiometric-thin layer chromatographic method. 2. Histamine and three of these drugs, namely cimetidine, ranitidine and famotidine, were weak inhibitors of this cytochrome P-450-catalysed O-deethylation, but mifentidine was a potent competitive inhibitor with a Ki in the range 40-70 microM. 3. Cimetidine, histamine and mifentidine are all 4(5)-substituted imidazole derivatives, and the contrast between the very weak inhibitory effects of cimetidine and histamine, and the more potent effect of mifentidine, suggests that the imidazole moiety may play little role in the inhibition of phenacetin O deethylase by mifentidine. 4. The demonstration that cimetidine, ranitidine and histamine were all poor inhibitors of phenacetin oxidation further suggests the possible lack of identity between the human liver cytochrome P-450 isoenzymes responsible for catalyzing the oxidation of metoprolol and phenacetin. This follows from recognizing that metoprolol oxidation is known, from both in vivo and in vitro studies, to be strongly inhibited by both of these H-2 receptor antagonists and from in vitro studies also to be inhibited by histamine. PMID- 2899933 TI - [Effect of physical training on the aerobic-anaerobic transition in chronic liver diseases]. AB - 7 males, aged 30 to 60 years, with bioptically ascertained chronic liver diseases underwent a four-week preservance training programme on the bicycle ergometer in the aerobic-anaerobic transitional area (performance at 2-4 mmol 1(-1) lactate). The training caused a significant amelioration of the aerobic functional capacity of the test persons. The hypothesis of a liver-protective effect of the perserverance training was confirmed. The inclusion of a dosed physical training in the therapy and rehabilitation programme, respectively, of patients with chronic liver diseases can be recommended, particularly, since there is no causal medicamentous therapy of chronic liver diseases possible at present. PMID- 2899934 TI - [Characteristics of research on the mechanisms of the conditioned reflex in higher invertebrate animals (gastropod mollusks)]. PMID- 2899935 TI - [Analgesia and sedation of ventilated patients in intensive care medicine]. AB - Any patient admitted to an intensive care unit requires individual analgetic and sedative treatment, depending on type and severity of the disease with its associated physical and psychic problems. There is a wide range of possible medicaments and combinations of these from among which the authors investigated combinations of the short-action opiates fentanyl and alfentanyl and midazolam, a benzodiazepine, short-action as well. These were tested for their effects on several circulatory parameters, intracranial pressure, wake-up behaviour, and selected hormonal parameters of mechanically ventilated patients. Both analgosedation schemes yielded best results, when compared to other combinations also continuously administered through perfusion. Individually adapted synchronisation of the patients to respirator and therapeutic concept proved to be practicable at any time, in spite of that fixed combination of analgetic with sedative. PMID- 2899937 TI - Drugs recently released in Belgium. Recombinant DNA yeast-derived hepatitis B vaccine-terazosin. PMID- 2899936 TI - Inhibition of the mitochondrial F1-ATPase by rose bengal mediated photooxidation. Interaction of the Fe2+ chelate of bathophenanthroline with the sensitizer. AB - Rose Bengal mediated photooxidation of mitochondrial F1-ATPase and its beta subunit resulted in inactivation and loss of about 50 and 60% of their histidine residues, respectively. The beta-subunit was not cleaved upon photooxidation. Photooxidation of histidine probably results in changes in the conformational stability of F1-ATPase leading to its inactivation. The participation of singlet molecular oxygen during the photooxidation process is suggested by the selective loss of histidine residues, while other amino acids, also sensitive to singlet oxygen attack, were not affected. Photochemical damage of F1-ATPase was prevented by various phenanthroline compounds, the order of efficiency being bathophenanthroline-Fe chelate greater than bathophenanthroline greater than orthophenanthroline-Fe chelate greater than bathophenanthroline-sulfonate-Fe chelate. The prevention by bathophenanthroline-Fe chelate of photochemical damage is interpreted on the basis of its interaction with the photosensitizer, Rose Bengal, probably implying a chemical reaction which decreases the actual concentration of the sensitizer and, thereby, the extent of photoinactivation. PMID- 2899938 TI - Sequential presentation of a case of hyperthyroidism with autonomously functioning nodules and Graves' disease in the presence of IgG thyroid stimulators. AB - The rare occurrence of hyperthyroidism with an autonomously functioning nodule which following 131I therapy presented as toxic diffuse goitre (Graves' disease) is described in a 60 year old male. This progression was characterised by the presence of varying concentrations of IgG thyroid stimulators, thyroid stimulating immunoglobulins and thyroid growth stimulating immunoglobulins, as measured by cytochemical bioassay. It is postulated that the presence of the nodule and its associated hypersecretion of thyroid hormones may have protected the gland from the effects of IgG stimulators by bringing about inhibitory short loop feedback on normal thyroid cells. It is further suggested that following therapeutic ablation of the nodule, normal thyroid cells became sensitive to the thyroid stimulators with the evolution of typical features of toxic diffuse goitre. PMID- 2899939 TI - Pituitary-dependent effects of estradiol-17-beta on catecholamine turnover rates, gamma-aminobutyric acid and glutamate concentrations in various hypothalamic and limbic brain structures. AB - Estrogens exert many effects in a variety of hypothalamic and mesolimbic structures. Whether the actions of the estrogens are direct or indirect, possibly involving anterior pituitary hormones, is largely unknown. We therefore studied catecholamine turnover rates, gamma-aminobutyric acid and glutamate concentrations in various hypothalamic and mesolimbic structures in estrogen treated hypophysectomized (hypox) rats and compared the measured parameters with those in sham hypophysectomized (sham) animals. Results clearly demonstrate that many of the effects of estrogen require an intact pituitary. Dopamine turnover rates in hypox rats were significantly reduced in the hypothalamus and the striatum, whereas they increased in the medial septum and medial preoptic area in comparison with sham rats. Norepinephrine turnover rates were reduced in the anterior mediobasal hypothalamus, somatosensory cortex and the nucleus accumbens of hypox animals in comparison with the sham-operated animals. In contrast, norepinephrine turnover was accelerated in the mediocortical amygdala and posterior medial basal hypothalamus of hypox rats. A significant reduction of epinephrine turnover was evident in the nucleus accumbens of hypox rats. Gamma aminobutyric acid concentrations increased in the medial septum, anterior and posterior part of the mediobasal hypothalamus, but decreased in the mediocortical amygdala of hypox animals. Concentrations of glutamate were also decreased in the mediocortical amygdala in hypox animals. These results indicate that many direct effects of estrogens in the brain are accompanied by indirect effects which require an intact pituitary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899940 TI - Response of luteinizing hormone secreting pituitary adenoma to a long-acting somatostatin analogue. AB - A large pituitary tumour was discovered in a 20 year old man who came to medical attention because of grand-mal seizures. The tumour produced biologically active LH as demonstrated by supranormal plasma LH and plasma testosterone values. Free alpha-subunit values were also elevated. In contrast, plasma FSH was in the lower normal range. Transsphenoidal operation failed to remove all tumour tissue. Detailed studies were carried out in the postoperative period. TRH and GnRH administration were associated with a rise of plasma LH and alpha-subunit, whereas plasma FSH was low and unresponsive. Bromocriptine treatment was ineffective. In contrast, both during and after treatment with SMS 201-995 for 6 weeks, a decrease of basal plasma LH values was observed. Furthermore, the administration of a single dose of SMS 201-995 reproducibly induced a decrease of plasma LH lasting for a period of about 6 h. The study suggests that SMS 201-995 may be useful in the treatment of patients with gonadotrope cell adenomas. PMID- 2899941 TI - A new approach in evaluation of fertility in surgically treated cryptorchids. AB - In this study twenty two operated cryptorchids were followed up (average period 12.02 years) and various indices of function like size, semen analysis and histology were assessed. FNAC as an index of spermatogenic potential of testis was added and compared with other investigations. The fertility potential in operated unilateral cryptorchids was 86.7 percent and in bilateral 42.9 percent. As an investigation in cryptorchids, FNAC correlated well with semen analysis and histology in all respects--the two gold standards. When done in a child FNAC would hence give an excellent idea of spermatogenic potential of that testis, regardless of age. We recommend that FNAC being the least traumatic but equally reliable modality should replace biopsy in the intraoperative as well as subsequent follow up evaluation of cryptorchids. PMID- 2899942 TI - Age-related changes in regulatory peptides in rectal mucosa. PMID- 2899943 TI - Vecuronium in the management of tetanus. Is it the muscle relaxant of choice? AB - Two cases of severe tetanus admitted to ITU with muscle rigidity and convulsions and needed mechanical ventilation had a continuous infusion of vecuronium as muscle relaxant. The cardiovascular changes of the two patients are described. It is concluded that vecuronium because of its minimal cardiovascular effects is the relaxant of choice in the management of severe tetanus. PMID- 2899944 TI - Medullary carcinoma of the thyroid. Common and uncommon morphological features. PMID- 2899945 TI - Management of medullary thyroid carcinomas. PMID- 2899946 TI - Three-dimensional arrangement of ductular structures formed by oval cells during hepatocarcinogenesis. AB - The three-dimensional arrangement of ductular structures formed by oval cells in rats fed 2-acetylaminofluorene (2-AAF) was studied by scanning electron microscopy (SEM) of biliary tract casts and light microscopy of sections of liver injected with india ink via the biliary tract. Both resin and india ink were well injected up to bile ductules, and the findings of each method correlated with each other. By the second week after 2-AAF administration, a few oval cells appeared in the periportal areas forming ductular structures which connected with the portal bile ducts. At the 4th week, increased ductular structures occupied two thirds of the lobule and formed networks communicating with each other, and with the portal bile ducts. At the 8th week, such ductular structures were compressed around hyperplastic nodules and appeared like a basket in biliary casts examined by SEM. Although a histochemical study of gamma-glutamyl transpeptidase revealed activity both on the luminal side of the ductular structures and hepatocytes in hyperplastic nodules, no transition was observed between these two cell populations. These results suggest that oval cells have characteristics more similar to those of biliary epithelia than of hepatocytes, and have no relation to the development of hyperplastic nodules. PMID- 2899947 TI - Neuroendocrine properties of the immune system. PMID- 2899948 TI - Kaposi's sarcoma and nitrite inhalants. PMID- 2899949 TI - Evaluation of amino acid neurotransmitters, related compounds, and precursors in dystonia. PMID- 2899951 TI - An evaluation of sustained postural abnormalities in rats induced by intracerebro ventricular injection of chlorpromazine methiodide or somatostatin as models of dystonia. PMID- 2899950 TI - Dystonia clinical research center tissue resource facility: investigations on collected tissue. PMID- 2899953 TI - Meige syndrome: primary and secondary forms. PMID- 2899952 TI - Animal models of neuroleptic-induced acute dystonia. PMID- 2899954 TI - Molecular genetics of an autosomal dominant form of torsion dystonia. PMID- 2899955 TI - Pharmacological consideration of intracavernous drug injection in the treatment of impotence. PMID- 2899956 TI - Antibody production against BLV-p24 in calves following application of cell extracts from tumorous lymph nodes of cattle with enzootic bovine leukosis. AB - In the cell extract from tumorous lymph nodes of bovine leukosis virus (BLV) infected cattle (tumour cell extract) and from lymph nodes of BLV-free cattle (control cell extract) neither the gp51 nor the p24 antigens were detectable. The tumour cell extract contained receptors for the BLV antigens gp51 and p24. The immunogenicity of the cell extracts was tested in calves. All calves treated with the tumour cell extract developed antibodies against p24 but not against gp51. Administration of the control cell extract, in contrast, induced no antibodies against p24. PMID- 2899958 TI - Resistance of mice to reinfection after E-aminocaproic acid treatment of primary influenza virus infection. AB - The effect of proteolysis inhibitors on the formation of resistance to virus challenge has been studied in experimental influenza of mice. E-aminocaproic acid (E-ACA) when used in the treatment of influenza decreased the virus reproduction in lungs and also enhanced the humoral immune response. The antibody titre on days 14 to 21 post infection (p.i.) was significantly higher in the treated animals. On day 30 after challenge with the homologous strain (H3N2) the virus reproduced to low levels in the lungs of untreated convalescent mice, but no virus was detected in the lungs of mice which had been treated with E-ACA during primary infection. Marked increase of the antibody level was found in such mice. Upon challenge with lethal doses of the virulent strain (H1N1), the protection was significantly higher among animals treated with E-ACA during primary infection with a sublethal virus dose. We believe that the immunomodulatory action of E-ACA may play an important role in the increased resistance to challenge exhibited by such treatment. PMID- 2899957 TI - Simultaneous determination of the level of antibodies to influenza virus surface and internal proteins by enzyme-linked immunosorbent assay. AB - Enzyme-linked immunosorbent assay (ELISA) has been adopted for simultaneous determination of the levels of antibodies to different influenza virus proteins in human sera with known haemagglutination-inhibition (HI) titre. Whole virus of serotypes H1N1 and H3N2, haemagglutinin (HA), matrix (M) and nucleoprotein (NP) proteins have been used as antigens. For detection of antibodies bound to the antigen, peroxidase labelled Staphylococcus protein A conjugate has been used. Correlation of the ELISA and HI titres of anti-HA antibody has been demonstrated. The use of isolated HA as antigen increased the specificity of ELISA. The analysis of human reconvalescent sera has shown that increase in the titre of antibodies to internal proteins does not always coincide with the increase of antibody level to HA. Out of 8 sera with significant increase of the HI titre to the H3 subtype 5 specimens showed 4-fold increase of antibody titre to NP protein. The antibody titre to M protein was elevated in 2 sera only, while 1 serum showed no rise of antibody response to the tested viral proteins. PMID- 2899959 TI - Comparative clinico-morphological investigations of the CNS of monkeys and of the eye teguments of guinea pigs infected with different measles virus strains. AB - Measles virus strains Edmonston and L-16 have been studied in 10 intracerebrally (i.c.) infected monkeys and in 155 guinea pigs infected into the anterior eye chamber. The strains appeared to differ in pathogenicity for monkeys and guinea pigs. The more pathogenic Edmonston strain caused encephalitis in monkeys, whereas in guinea pigs it caused iridocyclitis, keratoconjunctivitis and follicular conjunctivitis. Strain L-16 was not neurovirulent for monkeys, while in guinea pigs it caused follicular conjunctivitis. Specific pathohistological changes detected in the CNS of monkeys and in the eye teguments of guinea pigs were confirmed by virologic and serologic findings. PMID- 2899960 TI - Dependence on the birth season of the antibody level against West Nile virus in the Pakistani population. AB - Variation of antibody level against West Nile (WN) virus depending on the season of birth was followed among 151 paired serum samples of healthy Pakistani persons in Karachi, collected twice in July and October, 1985. The persons born during the months between February and June had lower positive antibody rate and lower responsiveness in haemagglutination inhibition and neutralizing tests against WN virus than those born during the other months. This phenomenon implies that the ability to produce antibodies against WN virus among Pakistani persons may depend on their birth season. PMID- 2899962 TI - Herpes simplex type 1 defective interfering particles do not affect the antiviral activity of acyclovir, foscarnet and adenine arabinoside. AB - The concentration of defective interfering particles (DI-particles) of herpes simplex type 1 virus was analysed by electron microscopy and plaque titration. Fifteen consecutive passages of undiluted virus in green monkey kidney cells were followed. No relationship was found between the concentration of DI-particles and the activity of antiviral substances such as acyclovir, foscarnet and adenine arabinoside. PMID- 2899961 TI - Human interferon alfa therapy and hepatitis B virus markers in the serum of patients with chronic course of illness. AB - Dynamics of serum levels of HBsAg, HBeAg and anti HBc were followed during human interferon alpha (Hu IFN alpha) therapy of patients with chronic active or chronic persistent hepatitis B. More or less expressed oscillations of HBsAg serum levels seen in two out of our six treated patients seemed to occur due to IFN effect. Little and seldom changes were observed in HBeAg and anti HBc serum levels. The profiles of HBsAg serum levels of interferon-treated patients compared with the profiles of "conventionally" treated patients disclosed occurrence of spontaneous or perhaps interferon-induced cyclic elevations and depressions of HBsAg blood levels. The possible significance of this phenomenon is discussed. PMID- 2899963 TI - Analysis of electrophoretypes of rotavirus from diarrhoeic faeces of neonatal buffalo calves in India. AB - Two distinct rotavirus RNA electrophoretypes were revealed by polyacrylamide gel electrophoresis followed by silver staining (PAGE-SS). The rotavirus was sampled from the faeces of buffalo calves in India from October, 1986 to January, 1987. In the buffalo farm under study one electrophoretype was prevalent first and then the second appeared after the disappearance of the first electrophoretype. For the detection of rotavirus in the diarrhoeic faeces of buffalo calves PAGE-SS was found more sensitive when compared with agar gel immunodiffusion and discontinuous counter immunoelectrophoresis tests. PMID- 2899964 TI - Induction of Epstein-Barr virus antigens by hydroxyurea. AB - Treatment of the Epstein-Barr virus (EBV)-transformed, virus-producer P3HR-1 cell line with hydroxyurea (HU) resulted in increased synthesis of the EBV-specific early antigen (EA) and viral capsid antigen (VCA). The induction was noted already at a 200 mumol/l and reached plateau at a 1500 mumol/l HU concentration. At plateau concentration, the percentage of cells expressing EA and VCA was about 5 times higher than in the absence of the drug. PMID- 2899965 TI - Detection of the antigen and antibodies to the eastern subtype of haemorrhagic fever with renal syndrome virus in small rodents in Slovakia. AB - Direct enzyme-linked immunosorbent assay (ELISA) was used for the demonstration of haemorrhagic fever with renal syndrome (HFRS) virus antigen in lung tissue of small rodents trapped in Eastern and Western Slovakia. The eastern subtype of HFRS virus antigen was demonstrated in the lungs of Apodemus agrarius and of the western subtype in the lungs of Microtus arvalis. Antibodies to HFRS virus antigen have been detected in Apodemus species (A. agrarius and A. flavicollis) in higher titres to the Eastern subtype. PMID- 2899966 TI - The role of cytoskeleton and nuclear matrix in virus replication. AB - In the light of the cytoarchitecture concept, the presented review attempts to cover what is known of the involvement of cytoskeletal and nucleoskeletal elements in the replication cycle of various viruses and in cell transformation. Our knowledge on the relationship of virus replication with cell architecture has rapidly progressed during the recent years in association with studies on composition of various filaments within cells, their spatial organization and possible functions which focussed much interest on the cytoskeleton and nuclear matrix. The new results indicated that highly specialized elements for normal cell function may be coopted for virus growth. Recently, using various methodical approaches it has been possible to obtain information about the association of virus-structural proteins with cytoskeletal and nucleoskeletal elements, about the reorganization of cytoskeleton during virus replication, about the role of tubulin in transcription and RNA synthesis of negative-strand viruses, about the involvement of cytoskeletal filaments in the transport of viral proteins, virus penetration, virus assembly and release from the infected cell. The role of cytoskeleton in cell transformation and in initiation of DNA synthesis and intracellular signaling to cell proliferation has been also investigated. PMID- 2899967 TI - Anti-LCMV immune serum preparation and its testing by complement fixation test and immunoelectroosmophoresis. PMID- 2899968 TI - First isolation of Soldado virus in southern France. PMID- 2899969 TI - Analysis of hamster lymphomas for the presence of hamster papovavirus DNA. AB - The hamster papovavirus (HaPV) is a polyomavirus isolated from skin epitheliomas arising spontaneously in young Syrian hamsters. It can induce lymphomas and leukaemias in newborn hamsters. Although no virus particles are detectable by electron microscopy, high amounts of monomeric and oligomeric forms of extrachromosomal HaPV DNA molecules are found in the lymphoma cells. These molecules display deletions of about 300 nucleotides in length. Their role in the lymphoma induction is discussed. PMID- 2899970 TI - Hemodynamic, renal, and neurohumoral effects of a selective oral DA1 receptor agonist (fenoldopam) in patients with congestive heart failure. AB - Fenoldopam mesylate (SK&F 82526-J) is a novel benzazepine derivative. It has selective agonist activity at post-junctional (DA1) vascular dopaminergic receptors, which normally subserve renal artery vasodilation. Previous studies in normal subjects and in patients with hypertension indicate that fenoldopam increases renal blood flow and promotes a sodium diuresis. Drug efficacy was clinically evaluated in eight patients with chronic congestive heart failure (CHF) after a single oral dose of 100 mg of fenoldopam and following 3 days of therapy (100 mg four times daily). Stroke volume index acutely increased from 26 +/- 7 (mean +/- SD) to 30 +/- 4 ml/beat/m2 (p less than 0.05) and left ventricular filling pressure decreased from 26 +/- 13 to 23 +/- 11 mm Hg (p less than 0.05). Systemic vascular resistance decreased from 1513 +/- 159 to 1128 +/- 319 (p less than 0.05). Hemodynamic changes were seen as early as 30 minutes following fenoldopam and returned to control levels by 4 hours. Forearm blood flow, hepatic blood flow, and venous capacitance did not significantly change acutely, but renal blood flow index was significantly reduced (34 +/- 4 to 30 +/- 3 min-1 X 1000, p less than 0.01). Plasma norepinephrine, plasma renin activity, plasma arginine vasopressin, and plasma aldosterone did not significantly change acutely. After 3 days of treatment, 100 mg of fenoldopam again reduced the renal blood flow index (35 +/- 7 to 26 +/- 7 min-1 X 1000, p less than 0.01) and tended to increase plasma renin activity (11.7 +/- 8 to 21.2 +/- 19.4 ng/ml/hr, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899971 TI - Beta-adrenergic blocker withdrawal syndromes in hypertension and other cardiovascular diseases. PMID- 2899972 TI - Gm typing by immunoglobulin heavy-chain gene RFLP analysis. AB - This study was undertaken to investigate a means of assigning Gm allotypes to Caucasians by RFLP analysis. A single immunoglobulin heavy-chain gamma-4 cDNA probe (HU gamma 4) was hybridized with genomic DNA digested separately with two restriction enzymes, TaqI and PvuII. Results showed excellent correlation (P less than .001) between serologically defined Gm allotypes G1m(1), G1m(2), G2m(23), and G1m;G3m (3;5,10) and RFLPs identified with the (HU gamma 4) probe. We conclude that it is now possible to define common Gm haplotypes in Caucasians by RFLP analysis. This method provides a useful adjunct to serological allotyping and indeed has several important advantages over traditional serology: it allows confident Gm assignment and the definition of homozygous and heterozygous Gm arrangements, is highly reproducible, and is readily executed in any molecular genetic laboratory. PMID- 2899973 TI - Recurrent parotitis with H2 receptor antagonists in a patient with Sjogren's syndrome. PMID- 2899974 TI - Parallel changes of atrial natriuretic factor and catecholamines during surgery for pheochromocytoma. PMID- 2899976 TI - Achondroplasia is not caused by mutation in the gene for type II collagen. AB - Achondroplasia is the most common human skeletal dysplasia. It is inherited as an autosomal dominant trait but the underlying biochemical cause is unknown. Genomic DNA from 49 affected individuals and two multiplex families with achondroplasia was studied using probes spanning COL2A1, the structural gene for type II collagen. Two lines of evidence speak against mutation in COL2A1 as the cause of achondroplasia: (1) no gross rearrangements are seen on Southern blot analysis of DNA from probands, and (2) linkage studies in multiplex families demonstrate discordant inheritance of achondroplasia and COL2A1 alleles. PMID- 2899975 TI - Ileal carcinoid tumor complicated by retroperitoneal fibrosis and a prolactinoma. AB - A patient with mid-gut carcinoid tumor and the unusual complication of retroperitoneal fibrosis was also found to have a prolactinoma. This case brings the number of reported mid-gut carcinoid tumors complicated by a second endocrine neoplasm to five. Three of the second tumors were parathyroid in origin, and the fourth was an insulinoma. In view of the rarity of second tumors and in the absence of documented familial occurrence, it is inappropriate to exhaustively study each person with mid-gut carcinoid tumor, or their families, for a second endocrine neoplasm; however, physicians caring for patients with mid-gut carcinoid should be aware that second tumors are possible. Retroperitoneal fibrosis is also a rare complication of carcinoid, but can be associated with renal failure that can be prevented by surgical intervention. Thus, physicians caring for patients with the carcinoid syndrome should also be aware of this complication. PMID- 2899977 TI - Comparative efficacy of the beta-blockers for the prevention of increased intraocular pressure after cataract extraction. AB - We conducted a randomized, double-masked study of intraocular pressure in 80 patients treated with betaxolol, levobunolol, timolol, or placebo after extracapsular cataract extraction. Intraocular pressures were measured preoperatively and early (four to seven hours) and late (20 to 24 hours) postoperatively. There was a significant mean increase in pressure from the preoperative period to the early postoperative period for the placebo group (5.35 mm Hg), betaxolol group (6.73 mm Hg), and the timolol group (3.83 mm Hg). However, the levobunolol group had a mean decrease in pressure (0.43 mm Hg). There was no significant difference between preoperative and late postoperative pressures for any of the groups. One-way analysis of covariance of the changes in pressure from the preoperative to early postoperative period showed a significant increase for the placebo and betaxolol groups compared to the levobunolol group, without significant difference between the levobunolol and timolol groups. Overall, levobunolol proved most effective in preventing an increase in intraocular pressure after extracapsular cataract extraction; timolol was partially effective. PMID- 2899979 TI - [Benzodiazepine and benzodiazepine antagonists in anesthesia and intensive medicine]. PMID- 2899978 TI - Human infections with Tensaw virus in south Florida: evidence that Tensaw virus subtypes stimulate the production of antibodies reactive with closely related Bunyamwera serogroup viruses. AB - Maguari virus, a member of the Bunyamwera serogroup (family Bunyaviridae, genus Bunyavirus) has not been isolated north of Trinidad. Anecdotal information from other investigators has indicated the presence of antibody to Maguari virus in human residents of south Florida. We attributed such antibody to either cross reactivity with Tensaw virus, the only Bunyamwera serogroup virus known in south Florida, or to cross-reactivity to an antigenic subtype or variant of Tensaw virus. Five strains, identified as Tensaw virus when they were isolated from mosquitoes collected in south Florida more than 20 years ago, were retrieved from storage. They were compared by serum dilution-plaque reduction neutralization tests with Bunyamwera serogroup prototypes Tensaw, Maguari, Cache Valley, and Tlacotalpan viruses. The south Florida isolates were shown to be most closely related to prototype Tensaw virus and most distantly related to prototype Maguari virus. One isolate could not be distinguished from prototype Tensaw virus, and the other 4 appeared to be subtypes of prototype Tensaw virus. More than 300 serum samples from humans in south Florida were tested for neutralizing antibody to prototypes Tensaw and Maguari viruses and to 3 of the field isolates. Thirteen had antibody to prototype Tensaw virus only, 19 to prototype Maguari virus only, and 39 to both. Antibody to all but 6 of these 71 was attributed to infection with Tensaw virus, to a subtype of Tensaw virus, or to travel or birth outside the United States. It is likely that those with antibody to Maguari virus only had been infected with yet another subtype of Tensaw virus, although another, undiscovered, Bunyamwera serogroup virus may exist in south Florida. PMID- 2899980 TI - [Effects and side effects of benzodiazepines]. AB - Due to the wide margin of safety and their pharmacological properties benzodiazepines are among the most widely used drugs in anaesthesiology and intensive care. Onset, duration and intensity of action depends mainly on their pharmacokinetic characteristics which exhibit some differences between the numerous compounds. All benzodiazepines possess dose-dependently anxiolytic, sedative-hypnotic, muscle relaxant and anticonvulsive properties. Likewise, the profile of side effects is almost identical, because all central actions of the benzodiazepines are based on a common molecular mechanism. CNS-depressant reactions, such as sedation, (hang-over) fatigue, ataxia, impairment of motor coordination and intellectual functions including memory (amnesia!) are most frequent, especially in the elderly if dosage has not been reduced accordingly. Rapid injection of higher doses should be avoided because these drugs (especially midazolam) can suppress ventilation. However, if benzodiazepines are properly used in patient-adjusted dosage they will represent valuable drugs in anaesthesiology and intensive care. PMID- 2899981 TI - [Benzodiazepines in premedication]. AB - Benzodiazepines have an anxiolytic, sedative, amnesic, muscle relaxant and anticonvulsive action. An analysis of the literature shows that benzodiazepines are the most important substances for premedication. They are preferred the evening before surgery for sleep induction. At the day of surgery they reduce stress better than any other substances or combinations. The different characteristics of different substances are presented. The way of application is discussed. Benzodiazepines, especially midazolam, offer new perspectives in the premedication of small children. Especially this group of patients remains to be a severe anaesthesiological problem. PMID- 2899982 TI - [Hemodynamic effects of benzodiazepines]. AB - Benzodiazepines are of major interest in anesthesiology and intensive care medicine; they are indicated world-wide pre-, intra- and postoperatively. Application of these drugs is influenced by their side-effects such as hemodynamic changes, limiting their indication. The paper is focusing on general hemodynamic changes caused by benzodiazepines; the most important intravenous derivatives are reviewed with specific reference to their hemodynamic profile. PMID- 2899983 TI - [The immune system and benzodiazepines]. AB - Alterations of the immune-system by benzodiazepines are of minor degree in dependence of their central or peripheral activity. Regarding their central effects a modulation may be assumed via the endocrine system. In vitro and in vivo studies lead to the assumption, that benzodiazepines have a mutagenic effect, even though this hypothesis could not be confirmed by in vitro investigations. In vivo a possible mutagenic action could only be found in two patients after long term therapy. A more mitosis-inhibiting effect of diazepam was shown in in vitro studies. In animal experiments this observation could not be confirmed for the thymus. With regard to specific immunity, diazepam seems to have a stimulating effect on the T-helper cells. Locomotion and chemotaxis of human polymorphonuclear granulocytes is not influenced by anaesthetic doses of benzodiazepines. It is questionable whether benzodiazepines are of clinical importance for the immune-system of patients receiving anaesthetic doses. However, the presently generous use of benzodiazepines, e.g. on intensive care units, should be reconsidered in respect to immunological consequences. PMID- 2899985 TI - [Antagonism of the effects of benzodiazepines using flumazenil (Ro 15-1788)]. AB - Flumazenil (Ro 15-1788) proved to be a very efficacious competitive antagonist of benzodiazepines that reliably counteracts their pharmacological actions within 1 2 min as could be demonstrated in clinical and EEG studies. In general, a total dose of 0.3-0.8 mg will be sufficient in clinical practice, avoiding side effects like nausea, tremor, sweating, or transient anxiety that could be observed when higher dosages were administered. Its therapeutic range is very high as could be demonstrated in experimental animal in which up to 8.000-fold the clinical dose was administered. The total volume of distribution (Vdes) amounts to nearly 1.000 ml/kg BW and the total clearance exceeds 1.200 ml/min, resulting in a biological half-life of less than 60 min. According to the benzodiazepine dosage and the rapid plasma concentration decline of flumazenil, in some cases a resedation could be observed. Hence, a careful observation of the antagonised patient on the ward is mandatory for 1.5-2 h, even if at first sight the antagonization seemed successful and the patient fully awake and cooperative. In anaesthesia, indications to administer flumazenil are adverse drug reactions and prolonged recovery after adequate benzodiazepine dosage. In intensive care medicine, the antagonist may be used in the treatment of benzodiazepine overdose as well as in the differential diagnosis of a coma of unknown origin. Additionally, the antagonist may be administered to interrupt benzodiazepine sedation e.g. for neurological examination. PMID- 2899984 TI - [Neurophysiological monitoring (electroencephalogram, evoked potentials) and the effects of benzodiazepines]. AB - Since the introduction of diazepam, flunitrazepam and midazolam into clinical practice benzodiazepines have been increasingly used for premedication, induction of anesthesia, and long-term sedation in the intensive care unit utilizing their anxiolytic and sedative components. Intraoperative monitoring of central nervous structures has to take into account the effects of benzodiazepines on the electroencephalogram (EEG) and evoked potentials (EP) before their contribution to alterations in brain electrical activity during balanced anesthesia with combination of different drugs can be evaluated. EEG reflects the spontaneous brain electrical activity whereas EP are the averaged time-locked electrical responses to external stimulation. They are thus able to assess the functional integrity of afferent neuronal pathways from peripheral nerves to cortical areas. The specific benzodiazepine antagonist flumazenil binds competitively to benzodiazepine receptors and is able to induce a change in pharmacodynamic parameters, which i.e. can be measured by EEG- and EP-recordings. Characteristical changes in the EEG after benzodiazepine medication consist in an activation of higher EEG-frequencies simultaneous to a decrease in alpha activity. A facultative increase in delta-activity seems to be dependent on the absolute dose administered and on the speed for intravenous injection. Benzodiazepine-induced EEG-alterations can be reversed by flumazenil almost completely but in the time course will change again in correspondence to the plasma levels of the benzodiazepines and the half-time of flumazenil. Cortical EP components are suppressed by benzodiazepines whereas subcortical generated potentials are not altered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899986 TI - Sinus arrest and beta blockade. PMID- 2899987 TI - [Energy and amino acid metabolism in the human brain under Disoprivan anesthesia with various paCO2 values]. AB - Propofol like thiopental and etomidate, suppresses cortical electrical activity in a dose-related manner, which leads to a 36% decrease in cerebral oxygen uptake and a 51% decrease in cerebral blood flow after an induction dose of 2 mg/kg followed by a maintenance dose of 0.2 mg/kg per min. In this study, the effects of propofol and varying paCO2 values on cerebral energy and amino acid metabolism were examined. METHODS. Eleven male patients between 49 and 63 years of age who were about to undergo coronary artery bypass surgery were studied. Measurements were performed with the patient awake (I), during steady-state maintenance anesthesia after propofol 2 mg/kg as an induction dose with 0.2 mg/kg per min by infusion with normocapnia (paCO2 39.9 +/- 3.1 mm Hg) (II), during hypocapnia (paCO2 29.9 +/- 2.6 mmHg) (III), and during hypercapnia (paCO2 50.6 +/- 3.3 mmHg) (IV). Cerebral blood flow was measured using the argon wash-in technique. A catheter was advanced into the superior bulb of the right internal jugular vein for measurement of cerebral oxygen, glucose, lactate, and amino acid uptake and release, which were calculated by multiplying the arterial-cerebral venous oxygen and substrate difference by the cerebral blood flow. Lactate/glucose index was calculated from the equation. Formula: see text. where a-vD lactate and a-vD glucose represent the arterial-cerebral venous substrate differences in mmol/l. Cerebral electrical activity was recorded by Fourier analysis of the EEG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899988 TI - [Onset of the effect and intubation conditions following atracurium, verocuronium and suxamethonium]. AB - 1. The onset of neuromuscular blockade following i.v. injection of atracurium 0.3, 0.4, or 0.5 mg/kg; vecuronium 0.08 or 0.1 mg/kg; and succinylcholine 1.0 mg/kg was studied in 205 adult patients during induction of anesthesia by means of the compound action potential (EMG) of the hypothenar muscle, which was indirectly stimulated via the ulnar nerve above the wrist, using the Datex Relaxograph. At the same time, the intubation conditions at 0.5, 1, 2, or 3 min after injection were assessed using a scoring system (Crul 1983) related to ease of laryngoscopy, movement of vocal cords and coughing, and reflex movements of the extremities. 2. Neuromuscular blockade and intubation conditions 2 min after administration of atracurium 0.3 mg/kg were 60 +/- 10% and 8.7 +/- 0.3; after 0.4 mg/kg 74 +/- 4% and 10.3 +/- 0.3; and after 0.5 mg/kg 86 +/- 5% and 11.8 +/- 0.2. After 0.08 mg/kg vecuronium 76 +/- 3% and 7.4 +/- 0.5 were recorded and after 0.1 mg/kg 85 +/- 6% and 10.5 +/- 0.4. Motor blockade 1 min after succinylcholine was 98 +/- 2% and intubation conditions scored 11.3 +/- 0.3. Relating intubation conditions to neuromuscular blockade yielded a close correlation and surprisingly good or very good intubation conditions (score more than 10) at a motor blockade of 80% (resp. 20% transmission). 3. Although succinylcholine is still the muscle relaxant with the most rapid onset of action, the new drug atracurium seems to satisfactorily facilitate tracheal intubation within an acceptably short time interval of 2 min after injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2899989 TI - Management of acute elevated intraocular pressure: Part II. Treatment. PMID- 2899990 TI - [Surgery of peptic ulcer 10 years after the introduction of anti-H2 agents]. AB - To evaluate the actual rate of both elective and emergency surgical operations for peptic ulcer, a questionnaire on the incidence of these operations was sent to 60 european departments of digestive surgery. 28 centers entered the trial, with the following results: 1,800 patients operated on; marked decrease of elective operations (100 percent of the centers); High decrease of emergency operations for hemorrhagic ulcer (80 percent of the centers). Decrease of emergency operations for perforation (50 percent of the centers). Decrease of operations for stenosis (70 percent of the centers). No-responders ulcers (ever more rare) and acute complications of patients with acute ulcer (elderly patients, under steroid or chemotherapy or intensive care) represent the resting indications to surgery. These results confirm the decline of surgery ten years after the introduction of H2 receptor antagonists. PMID- 2899991 TI - The influence of cysteamine and propionitrile on duodenal phosphoprotein phosphatase in rats. AB - Cysteamine and propionitrile cause severe duodenal ulcers with perforation within 24-48 h after a single injection in rats. These animal models were used to gain insight into the early, preulcerogenic biochemical changes in the duodenal mucosa. The results indicate that a single sc injection of cysteamine and propionitrile induced dose- and time-dependent decreases in the activity of phosphoprotein phosphatase (PPPase) in homogenate and particulate fractions of rat duodenal mucosa. The decrease in enzyme activity was detectable 4 h after the injection of the ulcerogens, it was maximal at 12 h, and hardly detectable at 24 h. No effect on the enzyme activity was found under in vitro conditions. PPPase activity in the liver was not influenced by either cysteamine or propionitrile. Furthermore, the toxic but nonulcerogenic derivative of cysteamine ethanolamine had no effect on PPPase in the duodenum. Thus, the effect of the duodenal ulcerogens on PPPase activity was indirect and organ specific, related only to the target organ (i.e., duodenal mucosa). The effect of the drugs was also selective at the level of mucosal cells: both duodenal ulcerogens depleted protein and alkaline phosphatase but not lysosomal acid phosphatase. The decrease of PPPase activity could be a general property of the duodenal ulcerogens since it is independent of their effect on endogenous somatostatin. PMID- 2899992 TI - Seronegative spondarthritis associated with Takayasu's arteritis. AB - A young woman presented with an aortic arch syndrome a few years after the onset of ankylosing spondylitis. Tissue typing showed HLA-B27. The possibility of an association between ankylosing spondylitis and Takayasu's arteritis is suggested. PMID- 2899993 TI - Growth hormone stimulates protein synthesis during hypocaloric parenteral nutrition. Role of hormonal-substrate environment. AB - The influence of growth hormone (GH) on protein metabolism and fuel utilization was investigated in eight paired studies of normal volunteers. GH (10 mg) was given daily during one period, and saline was injected during control studies. For 6 days, subjects received parenteral nutrition that provided adequate dietary nitrogen, vitamin, and minerals, but energy intake varied to provide 30-100% of requirements. On Day 7, the feedings were discontinued and an oral glucose load (100 g) was administered. The level of energy intake did not markedly influence the actions of GH. During nutrient infusions, GH caused positive nitrogen balance (1.0 +/- 0.3 g/m2/day vs. -1.2 +/- 0.3 in controls, p less than 0.001) and increased protein synthesis (16.8 +/- 0.7 g N/m2/day vs. 13.9 +/- 0.8, p less than 0.01). No change in the rate of protein breakdown or excretion of 3 methylhistidine occurred. GH was associated with an increase in insulin and insulin-like growth factor-I concentrations (IGF-I, 9.1 +/- 0.6 IU/ml vs. 3.3 +/- 0.5, p less than 0.001). After discontinuation of the parenteral nutrition and administration of the oral glucose load, glucose concentrations tended to be higher after GH; however, despite a two- to threefold increase in insulin response, muscle glucose uptake was attenuated (1.10 +/- 0.19 g/kg forearm vs. 1.64 +/- 0.30 in controls, p less than 0.05). Compared with control conditions, GH appeared to attenuate the increase in amino acid nitrogen efflux from muscle after the administration of oral glucose. These data demonstrate that the protein anabolic effect of GH, which occurs even during hypocaloric feedings, is related to multiple mechanisms that favor protein synthesis. These include the increase in plasma concentrations of GH, insulin IGF-I and fat utilization. GH administration results in a hormonal-substrate environment that favors nitrogen retention and protein synthesis. GH may be beneficial in promoting protein synthesis in surgical patients, particularly in association with hypocaloric glucose infusions that allow utilization of body fat as an energy source. PMID- 2899995 TI - Retrograde flow in the internal mammary artery. PMID- 2899996 TI - High-frequency ventilation during dissection of the internal mammary artery. PMID- 2899994 TI - Susceptibility of hamsters to caecal amoebiasis by oral infection. AB - A method is described for successfully establishing caecal amoebiasis in hamsters which were not fed and which were pretreated with 1 ml of magnesium sulphate every 24 hours for three days and then given 12 x 10(5) trophozoites of the HM-1 axenic strain or 18 x 10(5) trophozoites of the HK-9 axenic strain of Entamoeba histolytica by the oral route. All the animals developed diarrhoea within 24 hours of infection. When the animals were killed on the fifth day after infection the caecum was swollen and fused. Large macroscopic ulcers full of pus could be seen in the caecum. None of the control animals showed any of the changes mentioned above. PMID- 2899997 TI - [Circadian rhythm in myocardial infarct]. AB - In order to determine if the beginning of the Myocardial Infarction (MI) is at random along the day or if it follows a circadian rhythm, we analyzed the clinical charts of 819 patients admitted to the Coronary Care Unite. Among them, 645 were male and 174 female. It was established that the beginning of the MI follows a circadian rhythm with maximal frequency between 8 and 9 a.m. and minimal at 0 hours (p greater than 0.01). This rhythm is sex independent. In patients younger than 45 years as well as those who received beta-block agents in less than 24 hours previous the MI no circadian rhythm was observed. PMID- 2899998 TI - Possible involvement of receptors in the entry of Kunjin virus into Vero cells. AB - The results obtained from electron microscopy, adsorbed and internalised virus assays and immunofluorescence studies supported that the most likely mode of entry of Kunjin virus into Vero cells was by receptor-mediated endocytosis. This was deduced indirectly from the time sequence of events that occurred. Electron microscopy revealed that endocytosis of the virus through coated vesicles had occurred. The adsorbed and internalised virus assay and immunofluorescence studies showed that there were two factors being recycled during endocytosis: the receptor for the virus and clathrin, the protein found on coated pits and vesicles. The study showed that clathrin was recycled first, followed by the receptor. PMID- 2899999 TI - Immunocytochemical and ultrastructural characterization of human T-lymphotropic virus type I (HTLV-I)-producing rabbit lymphoid cell lines. AB - Fine structural and immunocytochemical characterization of rabbit lymphoid cell lines transformed by human T-lymphotropic virus type I (HTLV-I) was carried out. All nine cell lines tested were reactive with anti-HTLV-I-positive human, monkey, and rabbit sera and monoclonal antibody to HTLV-Ip 19, but not with anti-HTLV-I negative sera and monoclonal antibodies to human Ia and pan-T antigens. All cell lines were strongly positive for monoclonal antibodies to rabbit Ia and pan-T antigens. Ultrastructurally, each cell line contained C-type virus particles in varying numbers in the extracellular space. These particles showed replication patterns similar to those in HTLV-I or simian T-lymphotropic virus type I (STLV I)-producing human or monkey cells. In addition, anti-HTLV-I-positive rabbit serum gave positive immunoreactivity to HTLV-I or STLV-I by indirect immunoferritin method. These results indicate that the ultramorphology and replication patterns of HTLV-I in rabbit cell lines are indistinguishable from those of HTLV-I in human and monkey cell lines, HTLV-I in rabbit cells shares the common surface antigenic determinants with HTLV-I or STLV-I in human or monkey cells, and that these cells are definitely rabbit T cells bearing their own Ia antigens. PMID- 2900000 TI - Expression of pili and capsule by the avian strain P-1059 of Pasteurella multocida. AB - The avian strain P-1059 of Pasteurella multocida was grown on blood agar (BA), on dextrose-starch agar (DSA), or in Heddleston's hydrogen sulfide test broth. Cells were examined for the presence of pili using electron microscopy after staining with phosphotungstic acid, and they were examined for capsule after ruthenium red staining. Pili were found on the capsulated iridescent type, P-1059I, and on two non-capsulated variants, the blue, P-1059B, and the gray, P-1059G. Many cells grown on BA were heavily piliated. In contrast, fewer cells grown on DSA had pili, and piliation was only slight to moderate. The P-1059I, P-1059B, and P 1059G produced pellicles when grown on broth medium. Pili were found on the circumference of the cells grown on either agar or broth medium. Occasionally a pilus connecting two cells was seen on cells cultured in broth. Cultivation of the P-1059I on DSA containing the iron-chelating agent alpha,alpha'-bipyridyl produced a non-capsulated blue variant. The non-capsulated variant reverted to P 1059I when grown on BA but did not revert when grown on DSA. PMID- 2900001 TI - Vasopressin modulates the activity of nicotinic cholinergic mechanisms during memory retrieval in mice. AB - Lysine vasopressin (0.03 micrograms/kg, sc) enhanced retention test performance on a one-trial step-through inhibitory avoidance task when injected into male Swiss mice 20 min before the retention test. Tests were done 48 h following training. A low dose of the vasopressin antagonist AAVP (0.01 microgram/kg, sc, 20 min prior to testing) did not significantly affect retention test performance, whereas a higher dose (0.03 microgram/kg, sc) impaired it. Neither lysine vasopressin nor AAVP when given prior to testing modified latencies to step through of mice that had not received a footshock during training. The simultaneous administration of AAVP (0.01 microgram/kg, sc) prevented the enhancement of retention test performance induced by lysine vasopressin. The influence of lysine vasopressin on retention test performance was antagonized by the simultaneous administration of mecamylamine (5 mg/kg, sc) but not by hexamethonium (5 mg/kg, sc), atropine (0.5 mg/kg, sc), or methylatropine (0.5 mg/kg, sc). A modulatory role of vasopressin on the activity of central cholinergic nicotinic mechanisms which probably operate at the time of testing is suggested. PMID- 2900002 TI - Functional shift from muscarinic to nicotinic cholinergic receptors involved in inositol trisphosphate and cyclic GMP accumulation during the primary culture of adrenal chromaffin cells. AB - Specificities of cholinergic receptors for the accumulation of inositol trisphosphates (InsP3) and cyclic GMP and mobilization of intracellular Ca2+ in relation to culture periods were investigated in primary cultures of bovine adrenal chromaffin cells. At 0.5 day in culture, muscarine, a specific agonist for muscarinic receptors, caused a greater effect on intracellular Ca2+ mobilization and the accumulation of Ins(1,3,4)P3 than did the nicotinic-specific agonist nicotine. On the contrary, at 5 days, nicotine produced a greater effect on the accumulation of Ins(1,3,4)P3 and intracellular calcium mobilization than did muscarine. Furthermore, at 0.5 day, the muscarinic antagonist atropine strongly inhibited the increase in InsP3 accumulation that was induced by the nonspecific agonist carbachol, whereas at 5 days the inhibitory effect of atropine was greatly lowered. On the other hand, the nicotinic receptor antagonists hexamethonium and d-tubocurarine showed a much higher inhibitory potency at 5 days compared with 0.5 day in culture. Cholinergic receptor subtypes involved in cyclic GMP accumulation showed functional shifts similar to those in InsP3 formation. Binding experiments with a muscarinic ligand excluded the possibility that the reduction in muscarinic effects on InsP3 and cyclic GMP formation and intracellular Ca2+ mobilization were due to disappearance of the muscarinic receptor itself. These data show that cholinergic receptors linked to the accumulation of InsP3 and cyclic GMP and Ca2+ mobilization functionally shift from muscarinic to nicotinic during primary culture of adrenal chromaffin cells. PMID- 2900004 TI - Evidence for the bioactive conformation in a cyclic hexapeptide analogue of somatostatin containing a cis-peptide bond mimic. AB - N-methyl- alpha -benzyl-o-aminomethylphenylacetic acid was incorporated into a cyclic somatostatin analogue in order to mimic a cis-peptide bond configuration. The high biological potency of one of the isomers of the cyclic peptide strongly argues in favour of the proposed cis-configuration of the peptide bond at that position in the parent peptide. This represents the first cis-peptide bond mimic which has high biological activity. PMID- 2900003 TI - Chronic ethanol administration depresses fatty acid synthesis in rat adipose tissue. AB - Administration of ethanol as part of a nutritionally adequate liquid diet to female Wistar rats was found to depress markedly incorporation of labelled glucose into adipose-tissue acylglycerol fatty acids. Similar results with labelled pyruvate and acetate suggested inhibition of the fatty-acid-synthesis pathway at, or distal to, the acetyl-CoA carboxylase step. Activities of acetyl CoA carboxylase and fatty acid synthetase were markedly lower in ethanol-fed animals. The activity of another lipogenic enzyme, phosphatidate phosphohydrolase, was not affected by chronic ethanol feeding. These findings suggest that chronic ethanol administration has marked effects on adipose-tissue lipogenesis. PMID- 2900005 TI - Effects of azadirachtin on insect cytochrome P-450 dependent ecdysone 20 monooxygenase activity. AB - The effects of the insect growth and ecdysis inhibitor azadirachtin on ecdysone 20-monooxygenase activity were examined in three insect species. Homogenates of wandering stage third instar larvae of Drosophila melanogaster, or abdomens from adult female Aedes aegypti, or fat body or midgut from last instar larvae of Manduca sexta were incubated with radiolabelled ecdysone and increasing concentrations of azadirachtin and the ecdysone 20-monoxygenase activity quantified by radioassay. Azadirachtin was found to inhibit in a dose-response fashion the ecdysone 20-monooxygenase activity associated with all the insect preparations. The concentration of azadirachtin required to elicit approximately 50% inhibition of the ecdysone 20-monooxygenase activity ranged from a low of 1 x 10(-4) M for Drosophila to a high of 4 x 10(-4) M for Manduca midgut. PMID- 2900006 TI - Beta-endorphin modification by transglutaminase in vitro: identification by FAB/MS of glutamine-11 and lysine-29 as acyl donor and acceptor sites. AB - FAB-Mapping strategy was successfully exploited to characterize the reaction products of the transglutaminase-mediated modifications of human beta-endorphin in vitro. The GLN-11 residue of the neuropeptide was shown to be an effective acyl donor site for the enzyme, being able to bind spermine in the presence of Ca2+. Moreover, only one out of five lysyl residues (LYS-29) was demonstrated to act as acyl acceptor crosslinking with GLN-11. PMID- 2900007 TI - Palmitoyl carnitine: an endogenous promotor of calcium efflux from rat heart mitochondria. AB - The effects of the fatty acid ester palmitoyl carnitine (PC) on mitochondrial Ca2+ handling and ATP synthesis are described. At low concentrations (5-40 microM) PC was found to produce changes in mitochondrial Ca2+ handling, the most significant effect (P less than 0.05) being the promotion of Ca2+ efflux (EC25 = 1.19 +/- 0.11 microM). Studies on mitochondrial substrate oxidation in the presence of either glutamate plus malate, or succinate, confirmed the ability of PC (10-100 microM) to cause loss of respiratory control as shown by reductions in the Respiratory Control Index for each substrate. It was concluded that the effect of PC on Ca2+ transport was due to a direct action on the Na+-Ca2+ antiporter system, whilst the effect on respiration was due to an uncoupling action. PMID- 2900008 TI - Phorbol esters and thyroliberin have distinct actions regarding stimulation of prolactin secretion and activation of adenylate cyclase in rat pituitary tumour cells (GH4C1 cells). AB - The phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) enhances the effects of TRH on phase II of prolactin secretion as well as on hormone synthesis at both low and high TPA receptor occupancy. Furthermore TPA, but not the biologically inactive substance 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), stimulates the particulate bound adenylate cyclase with a time course paralleling that of TRH activation. However, the combined additions of TRH and TPA activate this cyclase in an additive manner while the Gpp(NH)p- and the forskolin sensitive enzyme are unaffected by TPA addition. Polymyxin B, which inhibits protein kinase C, abolishes activation of adenylate cyclase by TPA without interfering with the stimulatory action of TRH. Also, when phosphatase activity is preferentially inhibited by pretreatment of the cells with sodium vanadate, the TRH-sensitive cyclase is unaltered, while TPA activation is obliterated. Maximal stimulation of adenylate cyclase by cholera toxin pretreatment, obliterated the actions of TRH and TPA. Cells pretreated with pertussis toxin retained their TRH-sensitive cyclase, however, TPA-responsiveness was lost. We therefore suggest that the action of TPA as it relates to activation of adenylate cyclase, is probably mediated via the Gi component of the adenylate cyclase complex, while TRH stimulates the enzyme via the classical pathway involving the stimulatory GTP binding protein (Gs). PMID- 2900009 TI - Effects of heterocyclic amines in food on dopamine metabolism in nigro-striatal dopaminergic neurons. AB - We investigated the effects of 14 heterocyclic amines in food on nigro-striatal dopaminergic neurons. Among 14 compounds tested, 3-amino-1,4-dimethyl-5H pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P 2) caused substantial decreases in 3,4-dihydroxy-phenylalanine (DOPA) formation in striatal tissue slice system. When Trp-P-1 or Trp-P-2 was unilaterally infused in the rat striatum by an in vivo micro-dialysis technique, both compounds produced a transient increase of dopamine (DA) and continuous decreases in the metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the perfusate. This suggests that the two compounds inhibit monoamine oxidase (MAO) in vivo. Indeed they were found to be very potent inhibitors of MAO in vitro. Systemic administration of Trp-P-1 to C57 Black mice caused a marked decrease of DOPAC content and a significant increase of DA in the striatum, indicating inhibition of MAO in vivo. These results suggest that Trp-P-1 and Trp P-2 contained in food could alter the metabolism of DA in the brain. PMID- 2900010 TI - [Alkyl- and alkoxy-substituted lamtidine analogs: synthesis and H2-antagonistic activity. 38. H2-antihistaminics]. AB - In studies on the structure-activity relationships of histamine H2-receptor antagonists, lamtidine analogous derivatives of ortho-, meta- und para substituted piperidinomethylphenoxypropylamines bearing an additional substituent on the aromatic ring were prepared and tested for their H2-antagonistic activity on the isolated guinea-pig atrium. An additional substituent decreases the H2 antagonistic activity of the 3-(3-piperidinomethyl-phenoxy)-propylamine derivatives, while 2-membered substituents neighboring the connecting chain increase the activity of the ortho- and para-piperidinomethyl-substituted phenoxypropylamine derivatives. PMID- 2900011 TI - Absence of amnesia induction in mice with hydroxyzine in comparison with three other minor tranquillizers. AB - Hydroxyzine (Atarax) was compared with three traditional anxiolytics (diazepam, meprobamate, triazolam) for potential amnesic activity in a step-through passive avoidance task in the mouse. The doses investigated were: hydroxyzine (4, 8 and 16 mg/kg); diazepam (0.25, 0.5 and 1 mg/kg); meprobamate (8, 16 and 32 mg/kg); triazolam (0.0015, 0.003 and 0.006 mg/kg). The doses investigated were chosen on the basis of prior experiments for not having sedative effects as measured in a photo-cell activity meter. All drugs were administered i.p. 30 min before the first trial of the passive avoidance task. The compounds were also investigated for eventual analgesic activity using the hot plate test. The results indicated that hydroxyzine up to sedative doses was devoid of amnesic activity, whereas clear signs of amnesia were induced by diazepam, meprobamate and triazolam at doses at least 8 times lower than those which reduced spontaneous motor activity. None of the compounds showed analgesic activity in the hot plate test suggesting that the signs of amnesia observed in the passive avoidance test were not due to reduced sensitivity to aversive stimulation. PMID- 2900012 TI - Effect of food on absorption of chlordemethyldiazepam. AB - The kinetics of a single 1-mg oral dose of chlordemethyldiazepam (CDDZ, En) was determined on two occasions in 8 healthy volunteers. CDDZ was given in the fasting state on one occasion and following a standard meal on another. Compared with the fasting state, administration of CDDZ with food prolonged the time to reach peak concentration (1.5 vs. 6.8 h after dosage, p less than 0.01) and the absorption half-life (28 vs. 231 min, p less than 0.01). Total area under the curve was not influenced, nor was CDDZ elimination half-life (84.2 vs. 88.7 h). Thus administration of CDDZ with food slows the rate of its absorption but does not alter the completeness of absorption. PMID- 2900013 TI - [Long-term beta adrenergic antagonists in spastic bronchopathies]. AB - Beta-blockers are usually contra-indicated or reluctantly prescribed in cases of chronic obstructive bronchopathy. The aim of this study is firstly to show their tolerance in the long term in this pathology when the condition is stable and secondly to judge their efficacy in controlling side effects caused by bronchodilators (trembling, tachycardia) which are often administered at the same time. This study concerned 21 patients: 8 asthmatics and 13 spastic bronchitics, treated over a period of 4 months in a cross-over, double-blind test by 2 cardio selective beta-blockers (2 months: betaxolol, 2 months atenolol). During the study, respiratory tolerance proved to be good and side effects of bronchodilators were controlled. PMID- 2900014 TI - Intra-cerebral cysteamine infusions attenuate the motor response to dopaminergic agonists. AB - Previous studies have suggested that somatostatin neurons in the basal ganglia may be involved in motor activity. In the present experiments, the effects of cysteamine, a drug which reduces somatostatin levels, on the basal and dopamine mediated motor activities were examined in the rat. Neither intra-striatal nor intra-accumbens infusions of cysteamine had any effect on motor activity prior to the administration of dopamine agonists. However, intra-striatal cysteamine infusions reduced the duration of the stereotypic behavior induced by systemic apomorphine. In addition, intra-accumbens infusions of cysteamine produced a slight reduction in the locomotor response induced by amphetamine. The direct intra-cerebral infusion of cysteamine produced a significant depletion in the levels of somatostatin at the site of injections as measured by radioimmunoassay. These results indicate that somatostatin neurons in the basal ganglia may modulate the motor responses following dopaminergic activation, and further support the presence of a dopamine-somatostatin interaction in this region. PMID- 2900015 TI - Behavioral and neurochemical profile of the spontaneously diabetic Wistar BB rat. AB - The overall objective of the present investigation was to examine the behavioral and neurochemical profile of long-term diabetes (2-4 months), in the spontaneously diabetic Wistar BB rat (SDR). This animal model mimics the salient symptomatology of Type-I diabetes in man and circumvents confounds attributed to non-specific effects encountered in the chemically-induced models of diabetes. The first set of experiments were designed to investigate the effects of dopamine (DA) agonists and circadian cycle on the following spontaneous behaviors: locomotion, floor activity, rearing frequency and rearing duration. The results demonstrated that the SDR manifests (1) a blunted response to D-amphetamine (0.5 3.0 mg/kg; i.p.), and (2) lower levels of spontaneous locomotor and rearing activity in the latter part of the dark cycle, particularly at the transition of the cycle from dark to light. The next set of experiments assessed the status of brain catecholamine and metabolite levels in the insulin maintained and deprived SDR. The regional catecholamine and metabolite levels of the insulin-maintained SDR were not significantly different from those of the non-diabetic or the genetically distinct controls. However, the cessation of insulin administration to the SDR for 4 days resulted in significant increases in the levels of norepinephrine in the cortex and the hypothalamus, DA in the hippocampus, and homovanillic acid in the striatum. PMID- 2900016 TI - Human erythrocyte transglutaminase: purification and preliminary characterisation. AB - Erythrocyte transglutaminase was purified by anion-exchange chromatography, size exclusion and affinity chromatography. Homogeneity was achieved by an additional step of HPLC size-exclusion chromatography. The molecular mass of the purified enzyme was calculated to be 65,000 Da by size-exclusion chromatography and sucrose-gradient centrifugation, and 92,000 Da by SDS-PAGE, thus suggesting a high degree of asymmetry. The amino-acid composition of erythrocyte transglutaminase differed substantially from that of the guinea-pig liver enzyme, notably with respect to the number of histidine, cysteine and acidic amino-acid residues. The enzyme has an absolute requirement for divalent cations for activity: calcium, manganese, and the lanthanides terbium and gadolinium activate the enzyme in decreasing order of efficacy, while no activity is displayed in the presence of magnesium. In the presence but not in the absence of calcium ions, the enzyme is rapidly inactivated by N-ethylmaleimide and by diethylpyrocarbonate suggesting that the cation influences the reactivity of amino acids essential for catalysis. When erythrocyte proteins are employed as amine acceptors in the presence of calcium, the erythrocyte transglutaminase appears to preferentially modify membrane-associated proteins, although, in the absence of calcium ions and exogenous amines, it displays a pH-dependent interaction with soluble proteins. PMID- 2900017 TI - Studies on protein phosphorylation using subcellular fractions from insulin treated white adipose tissue of rats. AB - In these studies the incorporation of 32P into proteins within subcellular fractions, obtained from rat white adipose tissue upon incubation in the presence of [gamma-32P]ATP, was investigated. A stable increase in the activity of protein serine(threonine) kinase in high-speed supernatant fractions was observed following treatment of intact tissue with insulin. Protein kinase activity associated with the plasma membrane fraction of cells was diminished in response to insulin, but the decrease was apparently insufficient to account for increases observed in corresponding supernatant fractions. A range of assay conditions was employed to characterize the insulin-stimulated protein serine(threonine) kinase in in supernatant fractions. The insulin-stimulated protein serine(threonine) kinase displays properties that indicate it is distinct from a number of well characterized protein kinases, including those regulated by cAMP, calcium ions (in the presence or absence of calmodulin or mixtures of phosphatidylserine diacylglycerol), polyamines, or heparin. There were no apparent effects of insulin on incorporation of 32P into added casein or histones II-S or III-S. The protein serine(threonine) kinase activity (or activities) described here displays properties that also appear to differ from the properties of previously described insulin-stimulated activities able to catalyze the phosphorylation of the ribosomal protein S6. The differences in properties may, in part, be explained by the use of different cell types, but may also indicate that treatment of cells with insulin leads to activation of more than one protein serine(threonine) kinase. PMID- 2900018 TI - In vitro cross-linking of gluten into high-molecular-weight polymers with transglutaminase. AB - From the amino acid composition of gluten proteins and the substrate specificity of transglutaminases (TGase) we concluded that gluten proteins can be favourable substrates for TGases due to their high glutamine content. By use of sodium dodecyl sulfate polyacrylamide gel-electrophoresis it was demonstrated that from gluten-ES and gluten-TS high-molecular-weight proteins developed in the presence of Ca2+ and red blood cell lysate containing TGase. When ovalbumin or deamidated gluten were applied as substrates no high-molecular-weight products were formed. Upon spectrophotometric measurements we found that covalent cross-links (isopeptide bonds) formed under the effect of TGases presumably cause a change in the position of chromophore groups in the substrates. Absorption decrease was detected between 274-276 nm as a result in the case of gluten-TS and gluten-ES used as substrates for TGase. No such change occurred in ovalbumin and deamidated gluten, applied as controls, under the influence of TGase. On the basis of our experiments it is postulated that the first step in gluten toxicity is presumably the binding of gluten to the intestine mucosa. In this binding the high transglutaminase activity in the intestines of coeliac patients and the high glutamine content of gluten may have an important role. PMID- 2900019 TI - Mode of action of Clostridium perfringens initiation protein (spore-lytic enzyme). AB - The extracellular initiation protein (IP; spore germination enzyme) produced by Clostridium perfringens was further purified and characterized. IP hydrolysed spore cortical fragments with the release of free amino groups. End group analysis of hydrolysed fragments indicated the presence of N-terminal alanine but no reducing sugars. Molecular weight analysis of IP- and lysozyme-treated fluorescamine-labelled cortical fragments indicated that IP acts only on peptidoglycan chains containing cross-linked peptide subunits. IP failed to hydrolyse a number of nitrophenyl-conjugated glucopyranosides and galactopyranosides. The results indicate that IP is an N-acetylmuramyl-L-alanine amidase. PMID- 2900020 TI - A comparative serological and molecular study of linear IgA disease and dermatitis herpetiformis. AB - The class I and class II HLA serologically defined antigens and DQ alpha and DX alpha restriction fragment length polymorphism (RFLP) in 23 patients with linear IgA disease (LAD) were determined and their frequencies compared with those in a group of patients with dermatitis herpetiformis (DH) and healthy controls. In LAD there was a significant increase in HLA-B8 and DR3 and a larger increase in the DQw1-DR2/DRw6 related DQ alpha 6.2 kb and 6.8 kb RFLP. In DH there was a significantly increased frequency of HLA-A1, B8, DR3, and DQw2 with a concomitant increase in the DR3-DQw2 related DQ alpha 4.6 kb RFLP. The difference in DR3 frequencies and the increased frequency of DQw1 rather than DQw2 in LAD indicates that different susceptibility genes operate in the two diseases. PMID- 2900021 TI - Interim report of the Medical Research Council/Royal College of Obstetricians and Gynaecologists multicentre randomized trial of cervical cerclage. MRC/RCOG Working Party on Cervical Cerclage. AB - Overall 905 pregnant women whose obstetricians were 'uncertain' whether to recommend cervical cerclage, chiefly because of a history of early delivery or cervical surgery, were randomly allocated to cerclage or no surgery; 92% were treated as allocated. The overall preterm delivery rate was 30%. The results for those allocated cerclage were marginally statistically significant, more favourable in terms of fewer deliveries before 33 weeks [59 (13%) compared with 82 (18%), P = 0.03] and correspondingly for birthweight under 1500 g [48 (11%) compared with 73 (16%), P = 0.01] and for miscarriage, stillbirth or neonatal death [37 (8%) compared with 54 (12%), P = 0.06]. There were similar numbers of deliveries between 33 and 36 weeks [65 (14%) compared with 64 (14%)]. These results suggest that the operation had an important beneficial effect in one in 20 to 25 cases in the trial. But because the observed differences are not strongly statistically significant and because no such benefit has been seen in other randomized trials, there remains uncertainty about how much (if any) of this apparent benefit is real. So, the trial still remains open for randomization of more women whose obstetricians are uncertain about the advisability of cerclage. PMID- 2900022 TI - Inhibition by heparin of the oxidation of lysine in collagen by lysyl oxidase. AB - The generation of covalent cross-linkages in collagen is initiated by the deamination by lysyl oxidase of specific lysine residues in this connective tissue protein. Since lysyl oxidase activity is influenced by ionic ligands bound to its protein substrates, the effect of heparin, an anionic glycosaminoglycan known to bind to collagen, was explored by using collagen and elastin substrates and highly purified lysyl oxidase. Concentrations of heparin up to 1 mg mL-1 had little effect on the enzymatic rate of oxidation if it was added prior to the addition of enzyme to a preformed fibrillar collagen substrate or to an insoluble elastin substrate. However, collagen oxidation was inhibited by 85% if this glycosaminoglycan was present at 0.4 mg mL-1 during collagen fibril formation before addition of the enzyme. Similarly, the rate and extent of collagen fibrillogenesis in the absence of lysyl oxidase were each markedly inhibited in the presence of 0.4 mg mL-1 heparin. Heparin also inhibited the extent of tight binding of lysyl oxidase to preformed fibrils by about 40% under conditions where enzyme activity against preformed fibrils was hardly affected. These results suggest that heparin may modulate the oxidation and thus the insolubilization of extracellular collagen fibers, possibly under conditions where elastin fiber synthesis is not affected, and that the tight binding of lysyl oxidase to collagen is not completely related to the expression of enzyme activity toward this substrate. These results also have mechanistic implications for the retarding effect of heparin on postoperative wound healing. PMID- 2900023 TI - Amino acid sequence of guinea pig liver transglutaminase from its cDNA sequence. AB - Transglutaminases (EC 2.3.2.13) catalyze the formation of epsilon-(gamma glutamyl)lysine cross-links and the substitution of a variety of primary amines for the gamma-carboxamide groups of protein-bound glutaminyl residues. These enzymes are involved in many biological phenomena. In this paper, the complete amino acid sequence of guinea pig liver transglutaminase, a typical tissue-type nonzymogenic transglutaminase, was predicted by the cloning and sequence analysis of DNA complementary to its mRNA. The cDNA clones carrying the sequences for the 5'- and 3'-end regions of mRNA were obtained by use of the sequence of the partial-length cDNA of guinea pig liver transglutaminase [Ikura, K., Nasu, T., Yokota, H., Sasaki, R., & Chiba, H. (1987) Agric. Biol. Chem. 51, 957-961]. A total of 3695 bases were identified from sequence data of four overlapping cDNA clones. Northern blot analysis of guinea pig liver poly(A+) RNA showed a single species of mRNA with 3.7-3.8 kilobases, indicating that almost all of the mRNA sequence was analyzed. The composite cDNA sequence contained 68 bases of a 5' untranslated region, 2073 bases of an open reading frame that encoded 691 amino acids, a stop codon (TAA), 1544 bases of a 3'-noncoding region, and a part of a poly(A) tail (7 bases). The molecular weight of guinea pig liver transglutaminase was calculated to be 76,620 from the amino acid sequence deduced, excluding the initiator Met. This enzyme contained no carbohydrate [Folk, J. E., & Chung, S. I. (1973) Adv. Enzymol. Relat. Areas Mol. Biol. 38, 109-191], but six potential Asn linked glycosylation sites were found in the sequence deduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900024 TI - Effect of different insulin secretagogues and blocking agents on islet cell Ca2+ ATPase activity. AB - Plasma membrane Ca2+-ATPase activity was measured in rat islet homogenates. The enzyme was inhibited, in a dose-dependent manner, when the islets were preincubated for 5 min with different concentrations of glucose (2 to 16 mM). This inhibition disappeared almost entirely after 15 min incubation, regardless of the glucose concentration in the medium. Simultaneous measurement of insulin in the medium revealed a stimulatory effect of glucose upon insulin secretion. The Ca2+-ATPase activity was also inhibited when the islets were preincubated for 3 min with other stimulators of insulin secretion such as gliclazide (76 microM), tolbutamide (1.5 mM), glucagon (1.4 microM) + theophylline (10 mM) and ketoisocaproic acid (15 mM). Conversely, the activity of the enzyme was significantly enhanced when the islets were preincubated briefly with the insulin secretion blocker, somatostatin (1.4 microM). Neither glucose nor any of the other substances tested when added directly to the enzyme assay medium modified significantly the Ca2+-ATPase activity measured in the islet homogenates. These results would suggest that the activity of the islet plasma membrane is modulated by one or more of the intracellular metabolites produced when the islets are challenged by the insulin stimulator or blocking agents. PMID- 2900025 TI - Reaction mechanism of the reconstituted aspartate/glutamate carrier from bovine heart mitochondria. AB - A functional model for the aspartate/glutamate carrier of the inner mitochondrial membrane was established based on a kinetic evaluation of this transporter. Antiport kinetics were measured in proteoliposomes that contained partially purified carrier protein of definite transmembrane orientation (Dierks, T. and Kramer, R. (1988) Biochim. Biophys. Acta 937, 122-126). Bireactant initial velocity analyses of the counterexchange reaction were carried out varying substrate concentrations both in the internal and the external compartment. The kinetic patterns obtained were inconsistent with a pong-pong mechanism; rather they demonstrated the formation of a ternary complex as a consequence of sequential binding of one internal and one external substrate molecule to the carrier. Studies on transport activity in the presence of aspartate and glutamate in the same compartment (formally treated as substrate inhibition) clearly indicated that during exchange only one form of the carrier at either membrane surface exposes its binding sites, for which the two different substrates compete. In the deenergized state (pH 6.5) both substrates were translocated at about the same rate. Aspartate/glutamate antiport became asymmetric if a membrane potential was imposed, due to the electrogenic nature of the heteroexchange resulting from proton cotransport together with glutamate. Investigation of the electrical properties of aspartate/aspartate homoexchange led to the conclusion that the translocating carrier-substrate intermediate exhibits a transmembrane symmetry with respect to the (negative) charge, which again only is conceivable assuming a ternary complex. Thus, an antiport model is outlined that shows the functional complex of the carrier with two substrate molecules bound, one at either side of the membrane. The conformational change associated with the transition of both substrate molecules across the membrane then occurs in a single step. Furthermore the model implicates a distinct proton binding site, which is derived from the different influence of H+ concentration observed on transport affinity and transport velocity, respectively, when glutamate is used as a substrate. PMID- 2900026 TI - Effect of glycerol on gluconeogenesis in isolated rabbit kidney cortex tubules. AB - In renal tubules isolated from fed rabbits glycerol is not utilized as a glucose precursor, probably due to the rate-limiting transfer of reducing equivalents from cytosol to mitochondria. Pyruvate and glutamate stimulated an incorporation of [14C]glycerol to glucose by 50- and 10-fold, respectively, indicating that glycerol is utilized as a gluconeogenic substrate under these conditions. Glycerol at concentration of 1.5 mM resulted in an acceleration of both glucose formation and incorporation of [14C]pyruvate and [14C]glutamate into glucose by 2 and 9-fold, respectively, while it decreased the rates of these processes from lactate as a substrate. In the presence of fructose, glycerol decreased the ATP level, limiting the rate of fructose phosphorylation and glucose synthesis. As concluded from the 'cross-over' plots, the ratios of both 3 hydroxybutyrate/acetoacetate and glycerol 3-phosphate/dihydroxyacetone phosphate, as well as from experiments performed with methylene blue and acetoacetate, the stimulatory effect of glycerol on glucose formation from pyruvate and glutamate may result from an acceleration of fluxes through the first steps of gluconeogenesis as well as glyceraldehyde-3-phosphate dehydrogenase. As inhibition by glycerol of gluconeogenesis from lactate is probably due to a marked elevation of the cytosolic NADH/NAD+ ratio resulting in a decline of flux through lactate dehydrogenase. PMID- 2900027 TI - Somatostatin-28 and pro-ocytocin/neurophysin convertases: basic pair selective endoproteases involved in pro-hormone processing in the rat brain cortex and bovine corpus luteum. AB - Two neuropeptide precursor processing enzyme systems were characterized in the rat brain cortex and bovine neurohypophysis and corpus luteum. The first one combines the action of a 90 kDa endoprotease which cleaves somatostatin-28 before the Arg-Lys doublet and that of an aminopeptidase B-like enzyme. The second system associates the action of a 58 kDa endoprotease cleaving pro ocytocin/neurophysin (1-20) after the Lys-Arg dibasic moiety and a carboxypeptidase B-like activity. Both systems appear to be located in membrane limited secretory vesicles of the producing organs, and to exhibit the properties of metallo-enzymes sensitive to divalent cation chelators. In contrast, they do not show the characteristics of serine-proteases and of trypsin-like enzymes. Studies with substrate analogs selectively modified at the basic doublet indicated that the integrity of both basic amino acids is essential but that conformational parameters, probably governed by the amino acid sequences flanking the basic doublet, play an important role. These data will be discussed in relation to a hypothesis on the predicted preferred secondary structure of these restriction loci. PMID- 2900028 TI - Smoking and tardive dyskinesia. PMID- 2900029 TI - [Physiological role of pancreatic D-cells (mathematical study)]. AB - The physiological role of pancreatic D cells has been studied by the method of mathematical simulation. D cells were proved to produce a sparing effect both on B and A cells, bringing about a more economical secretory response to these cells. The suppression of insulin secretion by pancreatic somatostatin is substantial at lower glucose concentration and is insignificant at higher glucose concentration. Vice versa, the effect of D cells on glucagon secretion is especially considerable at higher glucose concentration, being slight at lower glucose concentration. The presence of D cells is absolutely necessary for the Langerhans islets to function as an organ regulating the deposition and mobilization of the biological fuel. PMID- 2900030 TI - Chromosome translocations involving band 7q35 or 7p15 in childhood T-cell leukemia/lymphoma. AB - In a chromosome study in childhood T-cell leukemia/lymphoma, we found t(7;11)(q35;p13) in 2 patients, t(7;14) (q35;q11) in one patient, and t(7;14)(p15;q32) in 1 patient. Southern blotting and in situ chromosomal hybridization studies in one patient with the t(7;11) demonstrated that both alleles of the T-cell antigen receptor beta-subunit gene (TCRB) were rearranged, and that one TCRB allele had relocated from 7q35 to the fusion point in band p13 of the involved chromosome 11 (11p-). These findings suggest that juxtaposition of TCRB with the putative oncogene tcl-2 located in band 11p13 may be a critical step toward development of this T-cell leukemia/lymphoma. In the other two translocations, all breakpoints were sites for lymphocyte function genes, ie, 7q35 for TCRB, 14q11 for T-cell antigen receptor alpha-subunit gene (TCRA), 7p15 for T-cell antigen receptor alpha-subunit gene (TCRG), and 14q32 for immunoglobulin heavy-chain gene (IGH). Thus, the findings in these cases allow us to expand the above hypothesis and propose that the juxtaposition of TCRB or TCRG with tcl-2, TCRA, or IGH through chromosomal translocation may activate a mechanism for the genesis of T-cell leukemia/lymphoma with these chromosome translocations. PMID- 2900031 TI - B-cell proliferative and differentiative responses after autologous peripheral blood stem cell or bone marrow transplantation. AB - In this study the authors have evaluated B-cell function after autologous peripheral-blood stem cell transplantation (ABSCT) and autologous bone marrow (ABMT) transplantation. The B-enriched fractions of peripheral blood from ten normal subjects and 22 autografted patients (11 patients after ABMT, eight patients after ABSCT, and three patients after ABSCT followed by ABMT) were investigated. Time postgrafting ranged from 1 to 34 months. Proliferative responses to anti-mu antibody, Staphylococcus aureus Cowan 1 (SAC), and low molecular weight (mol wt) 12-Kd B-cell growth factor (BCGF) were measured. Differentiative responses to the same factors were assessed by quantifying in vitro immunoglobulin (IgG/IgM) production. The authors found no difference in B cell function between the ABMT and the ABSCT patient groups. Compared to the B cells of normal subjects, only five out of 22 autografted patients showed a normal proliferative response to all agents used, while nine out of 22 did not respond to any signals. Eight out of 22 patients displayed various defects of B cell response. However, in vitro IgG/IgM secretion of predominantly IgG subclass was normal in 19 out of 22 patients. This in vitro ability to produce Ig was reflected by the patients' normal serum IgG/IgM levels, whereas serum IgA levels were low. The authors speculate that there may be 2 B-cell populations: the normal in vitro Ig production and in vivo serum IgG may come from the stimulation of a small number of re-infused pre-committed memory B cells while, in parallel, immature B cells develop from autografted hematopoietic progenitor cells. PMID- 2900033 TI - Brain damage and alcohol abuse: where do we go from here? PMID- 2900032 TI - Distribution of Ha-RAS-1 proto-oncogene alleles in breast cancer patients and in a control population. AB - The frequencies of 13 different Ha-ras proto-oncogene alleles have been estimated in 92 breast cancer patients and 60 unaffected individuals. The Ha-ras alleles can be identified using a DNA restriction fragment length polymorphism (RFLP) closely linked to the 3' end of the gene, and are characterized by a different length due to a region of sequences repeated a variable number of times (variable tandem repeats, VTR). The statistical analysis of the data obtained shows that the frequency of alleles ranging between specific length limits is significantly higher in breast cancer patients than in controls. The same applies to specific genotypes bearing the aforementioned alleles. This suggests that the inheritance of these alleles may be associated with an increased risk of developing breast cancer. PMID- 2900034 TI - The concurrent use of alcohol, cigarettes and caffeine in British benzodiazepine users as measured by a general population survey. PMID- 2900035 TI - Blockade of vasopressor and vas deferens responses by alpha,beta-methylene ATP in the pithed rat. AB - 1. The pressor responses produced by the intravenous administration of alpha,beta methylene ATP were tachyphylactic. 2. alpha,beta-Methylene ATP can attenuate pressor responses to sympathetic nerve stimulation both in the presence and in the absence of alpha-adrenoceptor blocking agents. 3. alpha,beta-Methylene ATP has no effect on the pressor responses produced by bolus injections of noradrenaline. 4. In the presence of alpha-adrenoceptor blocking agents, alpha,beta-methylene ATP further attenuates contractions of the vas deferens produced by nerve stimulation. 5. The results, together with previous data, suggest that the vasopressor response to stimulation of the sympathetic outflow in the rat is partly purinergic and partly alpha-adrenergic and that this occurs as co-transmission. The same applies to rat vas deferens, confirming in vitro data. The pithed rabbit had an alpha-blocker-resistant vasopressor nerve-mediated response but this was resistant to alpha,beta-methylene ATP. PMID- 2900036 TI - Vasodilator response to dopamine in the ferret pulmonary circulation. AB - 1. The isolated perfused lung of the ferret was used to study the effects of dopamine receptor agonists and antagonists. Under constant flow, a fall in pulmonary artery pressure reflects a vasodilator response. Since tone is normally low, agonists were given during hypoxic pulmonary vasoconstriction to enable detection of dilator responses. 2. Vasodilator responses were produced by bolus doses of dopamine over the range 0.1 to 5.0 micrograms kg-1, and by the selective DA1 agonist SK&F 38393 (1-phenyl-7,8-dihydroxy-2,3,4,5-tetrahydro-1H-3 benzazepine hydrochloride). 3. The dopamine response was blocked by low doses of the selective DA1-antagonist SCH23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl 5-phenyl-1H-3-benzazepine-7- ol maleate), and by sulpiride. 4. The vasodilator response to the relatively selective DA2-agonist N,N-di-n-propyl dopamine occurred only at high dose and was incompletely blocked by the selective DA2 antagonist domperidone at a cumulative dose of 10 mg kg-1. 5. Thus dopamine receptors of the DA1 type may mediate vasodilatation in the ferret pulmonary circulation, but no evidence was obtained for the existence of DA2-receptors. PMID- 2900037 TI - Correlation between log POCT/H2O and pKB estimates for a series of muscarinic and histamine H2-receptor antagonists. AB - 1. With histamine used as agonist, pKB values were estimated for seventeen histamine H2-receptor antagonists on assays involving acid secretion by the mouse isolated stomach and contraction frequency of the guinea-pig right atrium. 2. With the exception of oxmetidine, SK&F 94,826 and SK&F 94,206 on the right atrium assay, the compounds behaved as simple competitive antagonists on both assays. Although the former three compounds produced concentration-dependent, parallel, displacement of the histamine concentration-effect curves, subsequent analysis indicated Schild plot slope parameters significantly less than unity. However, the application of a combined dose-ratio analysis indicated that their antagonistic behaviour did not differ from expectations for simple competition at dose-ratios of approximately 20, and pKB values were estimated on this basis. 3. In accordance with previously reported data, pKB values were found to be consistently lower on the stomach than atrial assays. The pKB value for tiotidine was underestimated to the same extent on the stomach assay when impromidine was used as agonist. 4. The removal of the serosal muscle from the mouse stomach, achieved by using an isolated, perfused, mucosal sheet preparation, did not significantly affect the underestimation of the pKB value for metiamide. 5. Linear regressional analysis indicated a significant, positive, correlation between lipophilicity (log POCT/H2O) of the antagonists and the degree of antagonist pKB value underestimation on the gastric secretion assay. PMID- 2900038 TI - Bradykinin analogues: differential agonist and antagonist activities suggesting multiple receptors. AB - Bradykinin analogues with specific antagonist activity in several bioassays were evaluated for effects on [3H]-bradykinin receptor binding sites and inositol phosphate production in neuroblastoma N1E-115 cells. The analogues varied in their affinities for bradykinin receptors in guinea-pig ileum and N1E-115 cell membranes, in their effects on uterine and ileal contractions and in their agonist or antagonist activity on phosphoinositide turnover in N1E-115 cells. These tissue specific effects suggest the presence of multiple bradykinin receptor subtypes. PMID- 2900040 TI - Perspectives in the aetiology of seronegative polyarthritis. AB - The concept of seronegative polyarthritis is reviewed in relation to its clinical, immunogenetic, pathological and therapeutic features. PMID- 2900039 TI - The inhibitory effect of somatostatin peptides on the rat anococcygeus muscle in vitro. AB - 1. Electrically evoked contractions of the rat anococcygeus muscle were inhibited in a concentration-dependent manner by somatostatin-14 (SS14), -28 (SS28) and two synthetic hexapeptide analogues: L-363,301 (Pro-Phe-D-Trp-Lys-Thr-Phe) and L 363,586 (N-Me-Ala-Tyr-D-Trp-Lys-Val-Phe), with pIC50 values of 7.41, 7.38, 7.07 and 8.34, respectively. 2. The inhibitory effects of SS14 were dependent on stimulation frequency and external calcium ion concentration. Calcium behaved as a non-competitive antagonist of SS14, it reduced the maximal inhibitory effect of the peptide and at a concentration of 5.08 mM it significantly affected the pIC50 value. 3. SS14 (3 x 10(-7) M) did not affect the tonic actions of bath-applied noradrenaline in the absence of field stimulation. 4. The effects of SS14 persisted in naloxone (10(-5) M) and were, therefore, not due to an action at opiate receptors. Furthermore, experiments involving the lyophilization of bath contents, showed no evidence to support an indirect mechanism involving the release of an endogenous inhibitory substance. 5. High concentrations (10(-5) M) of SS14 or L-363,301 inhibited the relaxation response evoked by electrical stimulation of guanethidine (3 x 10(-4) M)-treated preparations. 6. These results are consistent with similar actions of SS14 on other smooth muscle preparations and are presumed to reflect a presynaptic inhibition of transmitter release by a direct action on somatostatin receptors. The antagonistic effect of calcium on this response is discussed with reference to a possible role in receptor desensitization. PMID- 2900041 TI - Lasertripsy for ureteric stones in 120 cases: lessons learned. AB - The pulsed dye laser has proved to be an effective and safe method of treating ureteric stones; 120 patients have been treated. Ureteroscopic lasertripsy (107 cases) had an overall success rate of 84%. The failures were due to mobile stones inadvertently flushed back into the kidney (14%) and 2% of patients required open ureterolithotomy after failure of two ureteroscopic procedures. "Blind" lasertripsy (13 cases) was safe but not as efficient, the success rate being only 23%. PMID- 2900042 TI - BRL 26830A and weight loss. PMID- 2900043 TI - Regulation of tyrosine hydroxylase and phenylethanolamine N-methyltransferase mRNA levels in the sympathoadrenal system by the pituitary-adrenocortical axis. AB - The pituitary-adrenocortical axis plays a complex role in the regulation of the levels of enzymes of the catecholamine biosynthetic pathway. In this report we have explored molecular mechanisms of these regulations, by examining the effects of hypophysectomy (HPX) and dexamethasone (DEX) on tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) mRNA levels in the adrenal medulla (AM) and superior cervical ganglia (SCG). Three weeks after hypophysectomy weights (-48%), total RNA (-49%), and DNA (-22%) contents in AM were significantly reduced, when compared to sham-operated animals (SO). In SCG decreases in weight (-23%) and in the ratio of RNA/DNA (-25%) were also found. TH mRNA contents paralleled decreases in total RNA levels and no significant change in the relative abundance of TH mRNA was found. When HPX rats were injected for 5 days with DEX (1 mg/kg, i.p.), TH mRNA levels in the SCG (+51%) and in the AM (+74%) were significantly increased when compared to saline-treated HPX animals. DEX given to SO rats increased TH mRNA in SCG (+49%); a 27% increase in TH mRNA in the AM was also observed. The relative abundance of PNMT mRNA in the AM was reduced after hypophysectomy (-64%). This decrease was completely reversed by DEX. In contrast, DEX did not affect PNMT mRNA levels in the AM of SO rats. PNMT mRNA was not detected in SCG of saline- or DEX-treated rats. In conclusion, our findings suggest that the pituitary-adrenocortical axis is involved in the regulation of the steady-state levels of TH and PNMT mRNAs. This regulation involves: (1) induction of TH mRNA contents in AM and SCG by increased plasma glucocorticoid levels; and (2) maintenance of the steady-state levels of PNMT mRNA in AM by glucocorticoid-dependent mechanisms. PMID- 2900044 TI - Histamine H1-receptors mediate phosphoinositide hydrolysis in astrocyte-enriched primary cultures. AB - Astrocyte-enriched primary cultures of newborn rat brain hemispheres, prelabeled with [3H]inositol, accumulated [3H]inositol phosphate but not [3H]inositol bis- and tris-phosphate, after exposure to histamine for 60 min in the presence of 10 mM LiCl. The response to histamine was not a function of contaminating meningeal fibroblasts since no accumulation of [3H]inositol phosphate was elicited by histamine in meningeal cultures. The stimulation of phosphoinositide hydrolysis by histamine in astrocytes was dose-dependent (EC50 = 1.7 microM, maximal effect = 345% over basal levels) and was mimicked by several H1-receptor agonists. The use of selective receptor antagonists confirmed that the histamine response was the result of activation of H1-receptors. The histamine-induced [3H]inositol phosphate accumulation was completely abolished by omission of Ca2+ from the incubation medium. Astrocyte membranes specifically bound the radiolabeled H1 antagonist, [3H]mepyramine with an affinity (Kd = 5.9 nM) and a density of binding sites (Bmax = 113 fmol/mg protein) similar to rat brain. These results demonstrate the presence of functional histamine H1-receptors in rat brain astrocytes and suggest a role for histamine as a neuromodulator of astrocyte function. PMID- 2900045 TI - The mechanism of cytosine arabinoside toxicity on quiescent astrocytes in vitro appears to be analogous to in vivo brain injury. AB - Neuronal cultures derived from the septal diagonal band region of the embryonic rat brain and grown in a chemically defined medium contained a very small number of contaminating astroglial cells. During the first week in culture, these cells were well dispersed in the form of a single isolated cell with fine fibrous branched processes. Treatment with 4 microM cytosine arabinoside for 24 h failed to kill these astrocytes (most probably present in quiescent form), as judged by glutamine synthetase activity and glial fibrillary acidic protein-positive cell count. On the other hand, the exposure of cultures to cytosine arabinoside resulted in a marked increase in choline acetyltransferase enzyme activity. The overall results, together with our previous findings, are consistent with the proposal that a brief exposure to a relatively low concentration of cytosine arabinoside induces quiescent astrocytes to produce a large quantity of a neurotrophic factor that is involved in the regulation of cholinergic cells. PMID- 2900046 TI - Role of microtubules in the cytoplasmic compartmentation of neurons. II. Endocytosis in the growth cone and neurite shaft. AB - We investigated the role of microtubules in the compartmentation of motility and endocytosis in the neurite shaft and growth cone of cultured chick sensory neurons. As reported previously by Letourneau and Ressler (J. Cell Biol., 98 (1984) 1355-1362), stimulating microtubule polymerization with taxol inhibits growth cone motility. In neurons that had grown for 18-30 h, taxol treatment caused growth cones to round up forming an obvious varicosity (taxol bulb) at the terminal. Removal of taxol allowed nearly immediate resumption of cortical motility in all 17 neurons observed by time-lapse videomicroscopy. However, only one of the 17 neurites was observed to elongate measurably even after 5 h of observation. In 14 cases taxol was rinsed out and the concentration of nerve growth factor was increased 10x, 11/14 neurites retracted within the next hour. Endocytic activity was investigated by incubating control and taxol treated neurons in either cationized ferritin or horseradish peroxidase for 30 min. The number and area of label-containing vesicles was measured along with the total area of the growth cone or taxol bulb. We found that taxol treatment caused a 7 fold decrease in the ratio of the area of the labeled vesicles to the area of growth cone or taxol bulb. Conversely, in neurite shafts, normally relatively quiescent with respect to endocytosis, those regions devoid of microtubules in both control and nocodazole-treated cells contained a high concentration of label containing vesicles. We conclude that the presence of microtubules plays a role in regulating endocytic activity by the overlying cell cortex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900047 TI - Differential afferent regulation of dopaminergic and GABAergic neurons in the mouse main olfactory bulb. AB - Peripheral deafferentation of the mouse main olfactory bulb following intranasal irrigation with ZnSO4 produced profound decreases in tyrosine hydroxylase activity and immunoreactivity in intrinsic dopamine neurons normally localized to the juxtaglomerular region of the bulb. In contrast, only modest alterations in GABA-immunoreactivity and glutamic acid decarboxylase (GAD) activity were observed in the same region. In fact, when GAD activity was expressed per mg tissue, a reflection of enzyme concentration, no changes in activity were observed 3 weeks postlesion and only relatively modest decreases in specific activity were found following long survival times (4 months). When the data were expressed per bulb, as an indication of the total amount of enzyme present, GAD activity and bulb weight exhibited similar reductions. Olfactory marker protein levels, determined as an indication of the completeness of the deafferentation, were at or below the limits of detection in all lesioned mice. These data indicate that afferent regulation of transmitter expression in the juxtaglomerular neurons of the olfactory system is phenotype specific. PMID- 2900048 TI - Effects of excitatory amino acids on the oxygen consumption of hippocampal slices from the guinea pig. AB - The effects of excitatory amino acids such as glutamate (Glu) and aspartate (Asp), and their receptor agonists, kainate (Ka), N-methyl-D-aspartate (NMDA), and quisqualate (Quis) on the neuronal activity and the oxygen consumption were investigated using hippocampal slices of the guinea pig. Bath application of these excitants elevated the amplitude of the postsynaptic field potential (PSP) to approximately 120% of the original level at low concentrations, although effective doses varied for the different excitants (Ka greater than NMDA greater than Quis greater than Glu greater than Asp). At concentrations over each effective dose the PSP was diminished and subsequently abolished. The application of Ka (1 x 10(-8) to 1 x 10(-6) M), NMDA (1 x 10(-8) to 1 x 10(-4) M), Quis (1 x 10(-7) to 1 x 10(-4) M), Glu (1 x 10(-5) to 5 x 10(-4) M), and Asp (1 x 10(-5) to 5 x 10(-3) M) enhanced the oxygen consumption dose-dependently, to a maximum of 120-146% of the resting level (8.43 mumol/g protein/min). It was notable that the initial increase in the oxygen consumption was associated with neuronal excitation and the doses of the excitants producing maximal oxygen consumption was in good agreement with those demonstrating disappearance of the PSP, probably because of massive depolarization of the neurones. The increase of the oxygen consumption and the neuronal activity induced by the excitants were specifically inhibited by their antagonists, such as glutamic acid diethylester (GDEE), DL-2 amino-5-phosphonovaleric acid (APV), and Joro spider toxin (JSTX). The present results strongly suggest that the enhancement of oxygen consumption due to the excitatory amino acids and agonists must reflect the neuronal activation induced by them. PMID- 2900049 TI - Role of somatostatin in the regulation of vasopressin secretion. AB - Intracerebroventricular (i.c.v.) administration of somatostatin-28 (SS-28) (30 ng 1 micrograms) resulted in a dose-dependent elevation of plasma concentrations of vasopressin. Continuous i.c.v. infusion of SS-28 produced a depletion of vasopressin-like immunoactivity within the paraventricular and supraoptic of the hypothalamus as determined by immunocytochemistry. To evaluate the role of endogenous brain somatostatin in the regulation of vasopressin secretion, animals were treated with cysteamine. Cysteamine (90 mg/kg) treatment given s.c. produced a 50% depletion of endogenous brain somatostatin-like peptide concentrations. Pretreatment of animals with cysteamine attenuated hemorrhage-induced elevation of plasma vasopressin levels. The elevation of plasma vasopressin concentrations following the i.v. administration of hypertonic saline or the i.c.v. administration of angiotensin-II were not altered by cysteamine treatment. These results are consistent with the conclusion that an endogenous brain somatostatin may be involved in the physiologic regulation of vasopressin secretion following hemorrhage. PMID- 2900050 TI - The response of striatal neuropeptide Y and cholinergic neurons to excitatory amino acid agonists. AB - The effect of excitatory amino acid antagonists on antagonist on neuropeptide Y (NPY) and cholinergic neurons in the striatum of the rat was studied by means of NPY immunocytochemistry, DFP histochemistry for acetylcholinesterase (AChE), and biochemical determinations of choline acetyltransferase (ChAT). Intrastriatal infusion of drugs revealed that striatal neurons containing NPY are more sensitive than cholinergic neurons to the neurotoxic actions of kainic acid (KA), quinolinic acid (QA) and L-glutamic acid (GA); all 3 compounds produced a marked loss of NPY neurons, but only a moderate decrease in the number of AChE neurons or ChAT activity. Co-injection experiments showed that the neurotoxicity of QA and GA, but not that of KA, can be antagonized by the specific N-methyl-D aspartate (NMDA) receptor antagonist 3-((+/-)-2-(carboxypiperazine-4-yl))-propyl 1-phosphonic acid (CPP). Destruction of the glutamatergic corticostriatal projection by cerebral decortication protected striatal NPY and cholinergic neurons against KA neurotoxicity. These results indicate that striatal NPY and cholinergic neurons receive prominent cortical amino acid afferents, and that the neurotoxic effect of QA and GA on these neurons is mediated through NMDA receptors. PMID- 2900051 TI - Neuropeptides and neuropathology in the amygdala in Alzheimer's disease: relationship between somatostatin, neuropeptide Y and subregional distribution of neuritic plaques. AB - This study examined the amygdaloid complex in Alzheimer's disease (AD). We compared the distribution and morphology of somatostatin (SOM-) and neuropeptide Y-immunoreactive (NPY-IR) neurons in the amygdala with the distribution of neuritic plaques (NP) and acetylcholinesterase (AChE) staining patterns in various subnuclei. We found that in AD, there was an increase in the number of small, atrophic neurons for both SOM and NPY, and subregional analysis revealed similar size reductions in all subnuclei. In contrast, the highest density of NP was found in the corticomedial nuclei and densest staining for AChE in the basal nucleus. Although NPY- and SOM-IR fibers were occasionally associated with NP, a dense, morphologically preserved peptidergic fiber-network was found in all areas including subnuclei with high numbers of NP. Our study indicates that atrophic SOM- and NPY-IR neurons are not correlated with the subregional distribution of NP or cholinesterase staining pattern of the amygdala, and suggests that alterations in SOM and NPY neurons are not characteristics of the primary pathogenic process that underlie the formation of NP or cholinergic cell loss in AD. PMID- 2900052 TI - Regional distribution of pre- and postsynaptic glutamatergic function in Alzheimer's disease. AB - Ca2+/Cl- -independent L-[3H]glutamate- and sodium-dependent D-[3H]aspartate binding assays were used to assess the integrity of N-methyl-D-aspartate (NMDA) receptors and glutamate uptake sites in a number of areas from control and Alzheimer's diseased brain. NMDA receptor densities were unchanged in all areas tested. In contrast, significant reductions in the number of glutamate terminals were seen in the hippocampus of the Alzheimer's samples. A smaller reduction was seen in the caudate nucleus but this failed to reach significance. No such reductions were seen in either the frontal or parietal cortices. PMID- 2900053 TI - Immunohistochemical evidence for a possible somatostatin-containing amygdalostriatal pathway in normal and Alzheimer's disease brain. AB - Somatostatin (SOM) immunohistochemistry was used to map SOM-containing fibers, perikarya and terminal-like structures in the human forebrain of 8 control and 8 Alzheimer's diseased patients. Immunohistochemically processed tissue revealed a somatostatin-immunoreactive amygdalostriatal fiber pathway apparently originating from SOM-positive neurons of the central amygdaloid nucleus. This pathway coursed dorsomedially between the optic tract and the internal segment of the globus pallidus within the ansa peduncularis-ventral amygdalofugal fiber system en route to the substantia innominata-nucleus basalis complex, the bed nucleus of the stria terminalis, the medial preoptic hypothalamic area, the nucleus accumbens and the olfactory tubercle. Somatostatin fibers associated with this pathway appeared as coarse heavily stained 'wooly fibers'. At the light microscopic level, there was no apparent difference in this somatostatin containing amygdalostriatal pathway between neurologically normal and Alzheimer's diseased brains. PMID- 2900054 TI - Cardiovascular responses elicited by electrical and chemical stimulation of the rostral medullary raphe of the rabbit. AB - Electrical stimulation of the rostral medullary raphe (RMR) of the rabbit elicited pressor responses that were accompanied by tachycardia or bradycardia. Stimulation of dorsal sites (the dorsal raphe obscurus) evoked a pressor/tachycardia response and stimulation of ventral sites (the ventral raphe obscurus, raphe magnus and raphe pallidus) produced a pressor/bradycardia response. Electrical stimulation of the RMR after sinoaortic denervation led to an increase in the magnitude of the pressor response elicited from all stimulation sites, a decrease in the magnitude of the bradycardia produced by stimulation at the ventral sites, but had no effect upon the magnitude of the tachycardia observed from stimulation of the dorsal sites. These findings suggest that electrical stimulation of the dorsal sites leads to inhibition of the cardiomotor component of the baroreceptor reflex. The results of vagal blockade experiments demonstrated that baroreceptor attenuation of the pressor responses at ventral sites was mediated primarily by parasympathetic input to the heart. Chemical stimulation of the RMR with L-glutamate also led to a pressor/tachycardia response at the dorsal sites and a pressor/brachycardia response at the ventral sites. This finding provides evidence that neuronal cell bodies, not axon of passage, mediated the responses elicited by electrical stimulation. PMID- 2900056 TI - Neurons of the subthalamic nucleus in primates display glutamate but not GABA immunoreactivity. AB - Immunohistochemical studies undertaken with a highly specific antiserum raised against gamma-aminobutyric acid (GABA)-glutaraldehyde-lysyl-protein conjugate showed that cell bodies of the subthalamic nucleus in the squirrel monkey (Saimiri sciureus) were closely surrounded by several GABA-positive terminals but were not themselves immunoreactive. In contrast, after incubation with a monoclonal antibody directed against carbodiimide-fixed glutamate, virtually all cell bodies of the subthalamic nucleus displayed an intense immunoreactivity. They were surrounded by various neuronal processes that also stained for glutamate. These results suggest that the neurons of the subthalamic nucleus in primates utilize the excitatory neurotransmitter glutamate instead of the inhibitory neurotransmitter GABA. PMID- 2900055 TI - Cholinergic brainstem sites for gain control of vestibulospinal reflexes in cats. AB - Decerebrate cats were injected with carbachol into the locus coeruleus (LC) or with carbachol or bethanechol into the dorsal pontine reticular formation (pRF) of one side; recordings were made of the tonic contraction of forelimb extensor muscles of both sides and of their responses to sinusoidal roll tilt of the animal. Both drugs had similar effects when injected into the pRF: a decrease in the tonic contraction of limb extensors and a greatly enhanced amplitude and gain with slightly decreased phase lead in the responses to animal tilt of the forelimb extensor, triceps brachii, ipsilateral to the side of injection. Injected into the LC, carbachol produced a response opposite to the above: it increased the tonic contraction of limb extensors ipsilateral to the side of injection, but decreased the amplitude and gain of the EMG responses of limb extensor muscles to labyrinth stimulation induced by sinusoidal tilt. These findings did not depend on changes in posture since they were still observed when postural EMG activity was maintained constant by appropriate changes in static stretch of the muscle. Moreover, the magnitude of the effects increased in a dose dependent manner. Results suggest that cholinergic activation of dorsal pRF neurons through muscarinic receptors increases the background discharge of medullary inhibitory reticulospinal (RS) system neurons, thus increasing their modulatory influence. Further, it is postulated that cholinergic activation of LC neurons would cause them to inhibit this tonic facilitatory drive by the pRF. Common to both sites of carbachol injection is the increase in phase lag of the EMG response of limb extensors to animal tilt.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900057 TI - Differential activation of spinal cord dynorphin and enkephalin neurons during hyperalgesia: evidence using cDNA hybridization. AB - A unilateral experimental inflammation of the hindlimb produces hyperalgesia to both mechanical and radiant thermal stimuli that is rapid in onset. During this period, parameters of dynorphin biosynthesis are elevated to a much greater degree than those of the enkephalin system. An increase in the content of the peptide dynorphin A(1-8) occurs in the spinal cord segments that receive sensory input from the affected limb. This is accompanied by a rapid (within 24 h) and pronounced increase in the levels of mRNA coding for the dynorphin protein precursor. Maximum elevations (6- to 8-fold) of preprodynorphin mRNA are observed between days 2 and 5 subsequent to the induction of inflammation. Compared to the increase in mRNA, the increase in dynorphin A(1-8) peptide was appreciably delayed and proportionately less; maximal increases in peptide (3-fold) were seen at day 5 of inflammation. Dorsal spinal cord preproenkephalin mRNA is elevated to a lesser degree (50-80%). However, the increase in preproenkephalin mRNA is apparently not enough to yield a measurable increase in the proenkephalin-derived peptide met5-enkephalin-Arg6-Gly7-Leu8, the levels of which showed no significant change during the 14-day inflammatory period. These data suggest the active participation of opioid neurons, especially those containing dynorphin, at the spinal level, in the modulation of sensory afferent input during peripheral inflammatory pain states. PMID- 2900058 TI - Chronic nicotine treatment counteracts the disappearance of tyrosine-hydroxylase immunoreactive nerve cell bodies, dendrites and terminals in the mesostriatal dopamine system of the male rat after partial hemitransection. AB - Male Sprague-Dawley rats were partially hemitransected at the mesodiencephalic junction and treated with nicotine (nicotine hydrogen (+)-tartrate) using Alzet minipumps implanted subcutaneously. Nicotine was delivered for 2 weeks in a dose of 0.125 mg/kg/h resulting in a serum nicotine level of 50.0 +/- 5.1 ng/ml. Three other groups of rats were analyzed: hemitransected rats receiving saline treatment and sham-operated animals receiving nicotine and saline, respectively. The effects of hemitransection and nicotine rostrally as well as caudally to the lesion were evaluated with image analysis of tyrosine hydroxylase (TH) immunoreactive (IR) nerve cell body and dendrite profiles in the rostral and caudal substantia nigra and of TH-IR nerve terminal profiles in the striatum. Adjacent sections were taken to Nissl staining. [3H]Nicotine binding in the midbrain and forebrain was studied by means of receptor autoradiography on partially hemitransected rats receiving no treatment. Catecholamine (CA) levels in the frontal cortex were measured using high-performance liquid chromatography (HPLC). Striatal dopamine (DA) function was analyzed studying apomorphine-induced (1.0 mg/kg) ipsilateral rotational behavior. The spontaneous behavior of the rats was evaluated with a hole board. Furthermore, body temperature and body weight were measured. The results demonstrated a lesion-induced disappearance of TH-IR cell body and dendrite profiles in the substantia nigra and of TH-IR nerve terminal profiles in the striatum. Similar findings were seen after Nissl staining. A significant counteraction of this disappearance was found in the nicotine-treated animals. On the lesioned animals a marked reduction of [3H]nicotine binding in the striatum and the substantia nigra was found. In the functional experiments an enhancement of the apomorphine-induced ipsilateral rotational behavior was demonstrated. The degree of rotation was positively correlated with the serum nicotine level. The study on spontaneous activity in the hole board showed a slower restoration of total activity in the hemitransected nicotine-treated rats. All these results are compatible with the hypothesis that the protective action of nicotine on the mesostriatal DA system may be due to a desensitization of excitatory nicotine cholinoceptors located on the nigral DA nerve cells, leading to a reduction of firing rate and reduced energy demands. Such an action of nicotine could be of importance for a possible anti-parkinsonian effect. PMID- 2900059 TI - Single thalamic dopaminergic neurons project to both the neocortex and spinal cord. AB - Cells in the rat subparafascicular thalamic nucleus (Spf) belonging to the diencephalic A11 cell group, were immunohistochemically stained with antibodies against tyrosine hydroxylase (TH) and dopamine itself. Employing a combination of retrograde fluorescent double-labeling and TH immunofluorescence techniques, we revealed the existence of dopaminergic Spf cells, giving rise to collateral projections to the neocortex and spinal cord. PMID- 2900060 TI - Ethanol potentiates GABA- and glycine-induced chloride currents in chick spinal cord neurons. AB - The effects of acute ethanol exposure of chick spinal cord neurons were studied in tissue culture, using whole-cell voltage-clamp techniques. Results indicate that ethanol produces a persistent increase in the sensitivity of spinal neurons to GABA and glycine, with no change in input resistance or resting membrane potential. Glutamate responses, in contrast, are unaffected by ethanol. PMID- 2900062 TI - The time of origin of somatostatin-immunoreactive neurons in the rat hippocampal formation. AB - Experiments utilizing a combination of [3H]thymidine autoradiography and immunohistochemistry were conducted to determine the time of origin of somatostatin-immunoreactive (SSIR) neurons in the hippocampal formation of the rat. A quantitative and topographic description of neurogenesis in this peptide containing neuronal system was generated using a computer-aided system to plot the position of labeled cells. Dissected and 'flattened' hippocampal preparations were used to facilitate the analysis of spatial gradients of SSIR cell development. The results indicate that most SSIR hippocampal cells are generated during a short embryonic period which extends from the 12th through the 15th day of gestation (E12-E15). Within this period of development, the distribution of SSIR cells follows a spatial gradient along the transverse or subiculo-dentate axis of the hippocampus. The earliest formed SSIR neurons, generated on E12 and E13, are preferentially distributed to the subiculum, those generated on E14 are most commonly observed throughout the CA1-CA3 fields of the hippocampus and SSIR neurons which become postmitotic on E15 are more heavily represented in the hilar region of the dentate gyrus than cells born at other stages of development. There was no clear-cut neurogenic gradient along the septotemporal axis of the hippocampus. These results indicate that somatostatin cells in the rat hippocampal formation are generated during the same prenatal period when glutamic acid decarboxylase (GAD)-positive neurons become postmitotic. These studies also suggest that quantitative developmental analyses of chemically specific cell types can reveal prominent features of cortical ontogeny that are not readily apparent in standard [3H]thymidine preparations. PMID- 2900061 TI - Morphological and physiological properties of rat cerebellar neurons in mature and developing cultures. AB - Immunohistochemical techniques and antibodies to gamma-aminobutyric acid (GABA), parvalbumin, and cyclic guanosine monophosphate-dependent protein kinase were used to identify populations of cerebellar neurons in culture that exhibit morphological features and immunoreactivity characteristic of neuronal types present in the cortical region of the cerebellum in vivo. The cultures were examined at 3 culture ages: 6-9, 12-15 and greater than 15 days in vitro, reflecting early, intermediate and late periods in cerebellar development. Neurons identified as Purkinje neurons (PNs), granule cells or inhibitory interneurons (stellate, basket, Golgi and Lugaro cells) were present at all culture ages. The granule cells (GCs) and inhibitory interneurons (INs) were morphologically well developed at the youngest culture age studied; morphological features did not change dramatically during the culture period. In contrast, the PNs were morphologically immature at 6-9 DIV (DIV = days in vitro) and exhibited dramatic changes in morphological structure with culture age. Extracellular recordings from PNs. GCs and INs in living cultures revealed that all classes of neurons exhibited spontaneous activity, but that only a portion of the GCs and INs were spontaneously active. The spontaneously active GCs and INs exhibited variable patterns of activity and low firing rates (approximately 2-6 Hz) at all culture ages studied. At 6 DIV, PNs exhibited firing rates and patterns similar to that of the interneurons. At older culture ages, the firing rate and pattern of PNs was significantly different from the GCs and INs and was characterized by high frequency (greater than 10 Hz) spike activity usually in a regular pattern. All cerebellar neurons by excited by the transmitter glutamate (Glu). The Glu response in the GCs and INs consisted of a brief burst of single spikes; in PNs, the response to Glu was prolonged and multiphasic. These data indicate that the cerebellar GCs and INs express morphological, physiological and developmental properties that are significantly different from the PN. PMID- 2900063 TI - The influence of neuronal cells on the development of glutamine synthetase in astrocytes in vitro. AB - The influence of neurons on the development of astroglial cells was examined in vitro using glutamine synthetase (GS) activity as an index of metabolic maturation. The GS activity in forebrain astrocytes was significantly increased (about 70%) when they were co-cultured with forebrain neuronal cells. A similar effect was also observed when astrocytes from the immature septum, hippocampus or cerebellum were co-cultured with neurons derived from the septal-diagonal band region. The magnitude of the effect was not uniform; the cerebellar astrocytes, with relatively low GS activity, showed a greater (about 290%) quantitative response to the subcortical nerve cells than did the septal (about 115%) or the hippocampal (about 120%) astroglial cells. The addition of conditioned medium derived from neuronal cultures or plating the cells on a substratum of heat killed nerve cells, elevated the GS activity of astroglial cells by 33% and 39%, respectively. Our results indicate that a trophic factor secreted by neurons and direct contact with the nerve cell matrix, are both involved in the regulation of the differentiation of astrocytes. PMID- 2900064 TI - Pain control during the intensive care phase of burn care. AB - Pain management in burned patients is a controversial topic. Early effective pain management in these patients requires that the physician and nurse be aware of the advantages and disadvantages of various pharmacologic and nonpharmacologic measures that may be used. Newer approaches to assessing and managing pain in these patients must be explored. PMID- 2900065 TI - MK 458, a selective and potent D2 receptor agonist in advanced Parkinson's disease. AB - MK 458 is a potent and selective D2 receptor agonist. MK 458 consists of (+)-4 propyl-9-hydroxynaphthoxazine (PHNO) in a hydroxypropyl-methylcellulose-lactose matrix. MK 458, mean dose 8.1 mg (range 2.5 to 13.5 mg), was administered to 14 patients with advanced Parkinson's disease (PD) who were no longer satisfactorily responding to levodopa. The duration of the study was 4 weeks with a titration to maximum dose in 2 weeks. The addition of MK 458 resulted in a mean reduction in levodopa of 41% (range 0 to 81%). This degree of levodopa reduction was not seen in previous studies with other DA agonists. While the reduction in signs of PD was comparable to those on levodopa, MK 458 did not induce dyskinesias or dystonias. It is postulated that MK 458 may be able to replace levodopa as the primary treatment for PD. PMID- 2900066 TI - Detergent-accelerated hydrolysis of bacterial endotoxins and determination of the anomeric configuration of the glycosyl phosphate present in the "isolated lipid A" fragment of the Bordetella pertussis endotoxin. AB - Due to the formation of micelles, severance of the hydrophilic (poly- or oligosaccharide) and hydrophobic ("Lipid A") domains of bacterial lipopolysaccharides at pH 3.4 or 4.5 and 100 degrees is slow and sometimes does not proceed at all; partially degraded fragments are usually formed. At pH 3.4 (100 degrees) in aqueous 1% sodium dodecylsulphate (SDS), both lipopolysaccharides of the Bordetella pertussis endotoxin are cleaved within 20 30 min, but 80% of the glycosidically bound phosphate present in the hydrophobic domain is lost. Other endotoxins behave similarly. At pH 4.5 (100 degrees) and in the absence of detergent, hydrolysis of the glycosidic bonds of 3-deoxy-D-manno-2 octulosonic acid residues of the B. pertussis endotoxin is negligible but, in aqueous 1% SDS, severance of the two regions of LPS 1 is complete within 1 h (that of LPS-2 requires 3-4 h), and the glycosidically bound phosphate of the isolated hydrophobic region is preserved. Comparison of the rate of acid catalysed hydrolysis of the glycosidically bound phosphate present in this "isolated Lipid A" preparation with that of 2-deoxy-2-[(3R)-3 hydroxytetradecanamido]-alpha- and -beta-D-glucopyranose 1-phosphates established that the former 1-phosphate was the alpha anomer. PMID- 2900067 TI - Synthesis of the glucuronide of carazolol. PMID- 2900068 TI - The pathophysiology and management of primary pulmonary hypertension. AB - Primary pulmonary hypertension is a relatively rare disease with a poorly understood pathophysiology, limited therapeutic options, and a dismal prognosis. The advantages and disadvantages of different pharmacologic approaches for this condition are discussed in this article. PMID- 2900069 TI - Beta-adrenergic blockade in children. AB - Beta-adrenergic blockers are often used in children to treat a variety of cardiovascular and noncardiovascular medical problems. The clinical experiences with beta-blockers in neonates, children, and adolescents are discussed in this comprehensive review. PMID- 2900070 TI - Cardiovascular drugs in pregnancy. AB - Cardiovascular drugs are often used in pregnancy for the treatment of maternal and fetal conditions. The complex physiologic changes occurring during pregnancy may significantly affect the pharmacokinetics of many drugs and, consequently, the toxicity and therapeutic response. Of special concern are the effects of maternal therapy on the fetus and the undesired translactal passage of drugs to newborns. Although the body of information regarding cardiovascular therapy in pregnancy is incomplete, some of the available data are summarized in this article. PMID- 2900071 TI - Dual regulation of ACTH secretion by guanine nucleotides in permeabilized AtT-20 cells. AB - 1. We have examined the effects of guanine nucleotides on ACTH secretion from digitonin-permeabilized AtT-20 cells, with the aim of analyzing the involvement of GTP-binding proteins (G proteins) in the secretory process. 2. AtT-20 cells permeabilized with 20 microM digitonin displayed calcium-dependent secretion. The EC50 of calcium was approximately 2 microM and the maximal stimulation was 350% of basal release. 3. Nonhydrolyzable guanine nucleotides also stimulated ACTH release, in a virtually Ca2+-free medium. The EC50 of guanosine 5'-(3-O thio)triphosphate (GTP gamma S) was approximately 15 microM and the maximal stimulation was approximately 230% of basal release. The effects of calcium and guanine nucleotides were not additive. 4. In the presence of the inhibitory hormone, somatostatin guanine nucleotides inhibited the calcium-stimulated secretion. 5. Both the stimulatory and the inhibitory effects on secretion of guanine nucleotides were independent of changes in cyclic AMP (cAMP) and calcium. It is suggested that G proteins influence an unknown step in the secretion process, which would be near or at the exocytotic site. 6. The results can be explained by assuming the existence of two types of G proteins, one with stimulatory effects on exocytotic release (GeS) and another with inhibitory effects (GeI). PMID- 2900073 TI - A role for the cytoplasmic domain in transferrin receptor sorting and coated pit formation during endocytosis. AB - The cytoplasmic domain of transferrin receptor (TR) is essential for endocytosis of this transmembrane protein. We have investigated by electron microscopy the association of wild-type and cytoplasmic deletion mutant human TR with coated pits at the surface of transfected L cell lines. Approximately 15% of wild-type TR was concentrated in coated pits, regardless of the level of TR expression. In contrast, only 2% of deletion mutant TR was present in these structures. We also correlated the frequency of coated pits with the level of TR expression in different transfected L cell lines. Expression of more than 3 x 10(6) wild-type TR per cell was accompanied by up to a 4-fold increase in coated pits compared with nontransfected Ltk- cells. No such increase was observed in a cell line expressing a similarly high level of cytoplasmic deletion mutant TR. These results indicate that the cytoplasmic domain plays an active role in sorting and endocytosis of TR by providing an assembly site for coated pit formation. PMID- 2900072 TI - Presynaptic regulation of dopaminergic transmission in the striatum. AB - 1. In vitro studies have indicated that several transmitters present in the striatum can regulate presynaptically the release of dopamine (DA) from nerve terminals of the nigrostriatal DA neurons. 2. The receptors involved in these local regulatory processes are located or not located on DA nerve terminals. 3. Recent in vivo investigations have demonstrated that the corticostriatal glutamatergic neurons facilitate presynaptically the release of DA and have allowed the analysis of the respective roles of presynaptic events and nerve activity in the control of DA transmission. PMID- 2900074 TI - The role of CD18 in phorbol ester-induced human monocyte-mediated cytotoxicity. AB - Monocyte cell surface molecules play an important role in the regulation of monocyte function. To investigate the molecular basis of monocyte-mediated cytotoxicity, we tested the ability of a variety of mediators to stimulate human monocyte-mediated cytotoxicity. Phorbol myristic acetate (PMA) stimulated significant monocyte-mediated killing of tumor cells in an 18-hr indium-111 release assay. Five other cytoactive substances did not induce monocyte-mediated cytotoxicity. The acquisition of monocyte cytotoxicity was associated with nearly a twofold increase in surface expression of three CD18-bearing cell surface molecules (CD11a, CD11b, CD11c). The direct involvement of the CD18-bearing molecules in monocyte-mediated cytotoxicity was investigated using monoclonal antibody (MAb) inhibition. MAb recognizing the CD18 subunit significantly inhibited monocyte-mediated killing. The inhibition by anti-CD18 MAb could not be attributed to LFA-1 (CD11a) alone, suggesting that CR3 (CD11b) and p150,95 (CD11c) may also participate in monocyte-mediated cytotoxicity. In contrast, seven of eight other cell surface structures were not affected by PMA treatment, and MAb to all eight cell surface structures did not inhibit killing. These findings suggest that CD18-bearing molecules are upregulated with monocyte activation and may play a functional role in monocyte-mediated killing. PMID- 2900075 TI - Foot and foot-related injuries in the young athlete. AB - This article discusses the more common pediatric problems of the foot associated with microtrauma. In the author's experience, most pediatric foot problems in sports are related to the biomechanics of the foot and lower extremity and most of their treatment is directed toward improving the immediate problem at hand and either at the same time or at a future time improving the biomechanics associated with the problem. It is the author's opinion that much of the macrotrauma is alos related to the biomechanical parameters of the foot type and lower leg function, indirectly or directly contributing to the mechanism of injury. This article elaborates on these mechanisms. PMID- 2900076 TI - Cloning, sequencing and analysis of the yeast S. uvarum ERG10 gene encoding acetoacetyl CoA thiolase. AB - The ERG10 gene specific to S. uvarum, a brewing yeast, has been cloned by complementation of an S. cerevisiae erg10 mutant. S. uvarum contains two different ERG10 genes. One of these is similar to the S. cerevisiae ERG10 gene; they are structurally different, but functionally homologous. The cloned ERG10 gene has been located on chromosome XVI, and we have shown that it is allelic to the previously isolated tsm0115 mutants. Northern blot and sequence analysis indicate that the ERG10 gene is highly expressed, and biochemical and genetic evidence show that it encodes the cytoplasmic acetoacetyl CoA thiolase. PMID- 2900079 TI - [Ultrastructural study of megakaryocytes in 4 patients with epidemic hemorrhagic fever]. PMID- 2900078 TI - Extensive restriction fragment length polymorphisms in a new isolate of Chlamydomonas reinhardtii. AB - A new field isolate of the unicellular green alga Chlamydomonas reinhardtii with useful properties for restriction fragment length polymorphism mapping is described in this report. The isolate, S1-D2 (mating type -), was the only strain found among 24 Chlamydomonas isolates taken from many locations which was interfertile with laboratory strains of C. reinhardtii. It mates at high efficiency, giving tetrads with excellent viability. Using cloned probes for both nuclear and chloroplast genes, we have found numerous restriction fragment length polymorphisms between S1-D2 and laboratory strains of C. reinhardtii. PMID- 2900077 TI - Isolation of a DNA fragment which complements glutamine synthetase deficient strains of S. pombe. AB - From a gene bank of S. pombe DNA, a 5.6 kb clone was isolated which complemented mutants defective in glutamine synthetase (GS) activity. Sub-cloning fragments of this 5.6 kb clone showed that the complementing activity was localised in a 1.6 kb HindIII-AvaI fragment and a partial DNA sequence revealed an open reading frame preceded by TATA sequences and a TGACTA sequence. Plasmid constructs carrying up to 3.4 kb of DNA used to transform gln- strains gave transformants which showed a wide range of GS activity, in some cases 100 times the wild-type level. These constructs identify DNA sequences lying downstream from the putative coding sequence which have effects on the total amount of enzyme activity, but do not affect the control imposed by the nitrogen source on which the cells are grown. PMID- 2900080 TI - [Monitoring of mosquito vectors at international airports of the South Pacific region]. AB - A survey conducted in eight airports of the South pacific, yielded 2,044 larvae and 136 adult forms, belonging to 25 Culicidae species. Breeding places were found in every airport, either within the perimeter (6 airports) or in the protective zone. Some potentially dangerous vectors were identified: Aedes aegypti (4 airports), Ae. polynesiensis, Ae. vigilax, Anopheles farauti (2 airports), Culex annulirostris, C. p. quinquefasciatus. Vector control measures should be strengthened to suppress every breeding place within the airport perimeter. PMID- 2900081 TI - [Sero-epidemiological study in Mauritania (1985-1986): incidence of treponematosis, hepatitis B virus, HIV virus and viral hemorrhagic fevers]. AB - A serological serosurvey was made in different ethnic groups of Mauritania in 1985. A very high prevalence of hepatitis B markers was found with more than 20% of HBs antigen carriers. Treponema specific antibodies in low-age classes observed is a reflect of endemic syphilis. The seroprevalence of antibody against HIV and viral haemorrhagic fever viruses (Rift Valley fever, Crimean-Congo haemorrhagic fever and haemorrhagic fever with renal syndrome) was very low. PMID- 2900082 TI - [Arboviroses in the region of Nosy-Be, Madagascar. Serologic and entomologic data]. AB - Since 1977, the Pasteur Institute of Madagascar has been studying, during six surveys, the arboviruses of Nosy-Be area, in the north-west of Madagascar. 47.2% out of 271 human sera and 11.3% out of 151 sera of Lemurs, tested for antibodies to 16 arboviruses by the haemagglutination inhibition test, are positive. The results show an important prevalence of Flaviviruses. West Nile and Dengue 1 viruses were probably circulating some years before the surveys. Antibodies against Sindbis and Rift Valley Fever viruses, were found only in few subjects. Bunyamwera and California groups of virus are absent. The rate of positive Lemurs is weak, particularly in Lemur macaco macaco. Flaviviruses are the most frequent. 12,262 haematophagous diptera (11,965 Culicidae belonging to 40 species) were caught. Aedes aegypti and Aedes albopictus are both present. Arbovirus isolation attempts from 394 mosquito pools failed; only Mengo virus was isolated from four pools of Eretmapodites quinquevittatus and one pool of Aedes (Skusea) sp. PMID- 2900083 TI - Large doses of vecuronium and plasma histamine concentrations. AB - The authors studied 20 surgical patients to determine the effect of large doses of vecuronium on plasma histamine concentrations. Patients were unpremedicated and anaesthetized with nitrous oxide and halothane via a mask. Tracheal intubation was performed without the use of muscle relaxants. Fifteen min later and before surgery had begun, vecuronium, in doses of 0.1 and 0.2 mg.kg-1 (n = 10 for each dose), was administered as an IV bolus. Arterial blood samples were obtained prior to and 2, 5, and 10 min after vecuronium administration and analyzed for plasma histamine by a radioenzymatic method. Arterial blood pressure and heart rate were measured continuously. In one patient who received 0.1 mg.kg 1 of vecuronium, plasma histamine concentrations at 2 min were 275 per cent of the control histamine value but fell below control at 10 min. This increase in plasma histamine was not associated with clinically important changes in blood pressure or heart rate. As a group, study patients had no significant changes in plasma histamine concentrations with either dose of vecuronium. In addition, mean plasma histamine values for each sampling interval did not differ between the two patient groups. Mean arterial blood pressure (MAP) decreased significantly at 10 min in patients receiving vecuronium 0.1 mg.kg-1, and at 2 and 10 min in patients receiving 0.2 mg.kg-1 of vecuronium. However, these decreases in MAP were not clinically important. Changes in plasma histamine concentrations did not correlate with corresponding changes in MAP. Heart rate did not change significantly in any patient during the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900086 TI - Cancer promoting potential of different strains of Fusarium moniliforme in a short-term cancer initiation/promotion assay. AB - A short-term cancer initiation/promotion bioassay was established to screen 10 toxic strains of Fusarium moniliforme for their cancer promoting activity in rats. The assay consisted of a four week 'promoting' treatment, effected by incorporating culture material (5%) of each strain into the diet, commencing one week after an initiation treatment with diethylnitrosamine (DEN, 200 mg/kg). The appearance of gamma-glutamyltranspeptidase-positive (GGT+) foci was used as an indication of promoting activity. Three out of 10 strains of F. moniliforme obtained from corn from a high risk area for esophageal cancer in Transkei, southern Africa, had significant cancer promoting activity. A highly significant correlation was found between toxicity expressed as reduction in body weight gain and cancer promoting activity. This finding suggests that the compounds responsible for the hepatotoxicity and hepatocarcinogenicity of F. moniliforme could be identical. PMID- 2900084 TI - Low-dose sufentanil as a supplement to halothane/N2O anaesthesia in infants and children. AB - Sufentanil as a supplement to halothane/N2O anaesthesia was evaluated in 32 unpremedicated infants and children age 6 months to 9 yr undergoing elective orthopaedic surgery. Patients were randomly assigned in a double-blind manner to receive one of four intravenous supplements: placebo, sufentanil 0.5, 1.0 or 1.5 micrograms.kg-1. Systolic arterial pressure (SAP), heart rate (HR) and end-tidal halothane concentration were recorded before and after induction, supplement administration, tracheal intubation, incision and every 15 min during the procedure. Venous catecholamine samples were obtained before and after incision. A pain score was assigned to the patients in the postanaesthesia care unit (PACU). Sufentanil at all three doses prevented increases in SAP and HR with intubation and incision, provided superior pain relief in the PACU and did not prolong wake-up time. Sufentanil 1.0 and 1.5 micrograms.kg-1 allowed for a reduction in the halothane requirements. Sufentanil 1.5 micrograms.kg-1 was associated with lower catecholamine levels than in the placebo group following incision. Sufentanil supplementation at 1.0 and 1.5 micrograms.kg-1 was associated with bradycardia and/or hypotension during induction and an increased incidence of vomiting during the first 24 hours postoperatively. One patient in the sufentanil 1.0 micrograms.kg-1 group whose surgical time was less than 45 min exhibited respiratory depression in the PACU requiring narcotic reversal. In conclusion, sufentanil 0.5 micrograms.kg-1 improved immediate postoperative pain relief and is acceptable as a supplement during halothane anasethesia in infants and children. The associated side effects of larger doses of sufentanil (1.0 and 1.5 micrograms.kg-1) make their use as a supplement to halothane anaesthesia unacceptable. PMID- 2900085 TI - Pre-treatment with somatostatin in the anaesthetic management of a patient with carcinoid syndrome. AB - Carcinoid syndrome produces flushing, bronchoconstriction and gastrointestinal hypermotility secondary to serotonin, histamine, bradykinin and prostaglandin release. A variety of drugs, foods and anaesthetic agents may provoke this syndrome. Under anaesthesia, the flushing produced may be associated with acute hypotension and cardiovascular collapse; this phenomenon is called a carcinoid crisis. Recently, somatostatin analogue has been used successfully to treat intraoperative carcinoid crisis. In this report, we present a 66-year-old lady with carcinoid syndrome who was pre-treated with 50 micrograms somatostatin analogue IV and IM prior to surgical manipulation. The anaesthetic course was relatively uneventful and the patient did well postoperatively. PMID- 2900087 TI - On standardization of the radioreceptor assay for anti-thyrotropin receptor antibody. PMID- 2900088 TI - Prenatal treatment: medical and gene therapy in the fetus. PMID- 2900089 TI - Scintigraphic portrayal of the syndrome of multiple endocrine neoplasia type-2B. AB - The scintigraphic appearance of the neoplasms in multiple endocrine neoplasia type 2B (MEN-2B) and the interpretations of the image patterns are described. An 18-year-old male patient with the MEN-2B syndrome underwent TI-201 imaging that showed concentrations of TI-201 in the primary medullary thyroid carcinoma (MTC) tumor and in cervical lymph node metastases. After total thyroidectomy and lymph node dissection, the TI-201 image was normal. Catecholamine levels in the blood and urine were only borderline elevated. Yet, greater than normal concentrations of I-131 metaiodobenzylguanidine (I-131 MIBG) were present in both adrenal glands. Computed tomography of the abdomen showed normal adrenal glands. These results were consistent with the diagnosis of adrenal medullary hyperplasia, a precursor of pheochromocytoma. No operation was indicated to remove the adrenal glands. Imaging with TI-201 appears to be useful in identifying sites of MTC in patients with the MEN-2B syndrome. I-131 MIBG imaging, in conjunction with computed tomography of the adrenal glands and appropriate catecholamine measurements, should be performed in patients with the MEN-2B syndrome to determine the status of the adrenal medullae, which then may be classified as normal, hyperplastic, or tumorous with pheochromocytoma. PMID- 2900090 TI - Somatostatin increases hepatic insulin extraction. AB - Somatostatin has been widely employed in studies of hepatic metabolism to suppress the endogenous secretion of the pancreatic hormones, insulin and glucagon. The possibility of somatostatin having hepatic effects has been considered before, but not decisively demonstrated. Eleven anesthetized dogs were used to assess the effect of somatostatin on hepatic insulin extraction (HIE) and hepatic glucose production (HGP). Insulin was infused by peripheral vein alone and during somatostatin (800 ng/kg/hr) in one series (I) of experiments and in the reverse sequence in another series (II). Portal vein and hepatic artery blood flow were measured electromagnetically, and blood samples were taken from the hepatic artery, portal vein, hepatic vein and a peripheral vein. HIE was increased in the presence of insulin plus somatostatin infusion. The combined results in Series I and II were 72.0 +/- 3.0% compared in insulin alone (64.0 +/- 4.0%, p less than 0.01). HGP was decreased in the presence of insulin and somatostatin infusion compared to insulin infusion alone both in Series I and II (1.71 +/- 0.25 to 3.72 +/- 4.0%, combined results, p less than 0.01). Whether this reduction in HGP indicates a direct effect of somatostatin on the liver, in addition to the inhibition of glucagon secretion, remains to be clarified. However, a decrease in hepatic glucose production is consistent with increased insulin extraction during somatostatin observed in the present study. We conclude that somatostatin increases the hepatic extraction of exogenous insulin. This effect of somatostatin is associated with decreased hepatic glucose production. PMID- 2900091 TI - Some evolutionary relationships of the primary biological catalysts glutamine synthetase and RuBisCO. PMID- 2900092 TI - The origins of Comparative Biochemistry and Physiology (written in celebration of the 40th anniversary year of the foundation of Pergamon Press, 1948-1988). PMID- 2900093 TI - Temperature mediated processes in teleost immunity: differential abilities of channel catfish T and B lymphocytes to cap membrane antigen. AB - 1. The effect of both in vivo acclimation temperature and in vitro assay temperatures on channel catfish T and B lymphocyte membrane antigen (mAg) capping were investigated to determine if capping might be the temperature sensitive step involved in the low temperature immunosuppression of channel catfish T cell responses. 2. Flow cytometry was used to monitor the kinetics of capping induced by a mouse monoclonal antibody (mAb 11G3) specific for a common antigenic determinant present on channel catfish T and B cells. Results indicated that the kinetics of mAg capping were dependent on in vitro assay and in vivo acclimation temperatures and the length of time of in vivo acclimation. 3. T cells from fish appropriately acclimated to 27 degrees C cap mAg more efficiently at low assay temperatures than do B cells. 4. Activation energies were 32 and 47 kcal/mol for B and T cells, respectively, from fish acclimated to 17 degrees C for 3 weeks, but were significantly lower (14 and 22 kcal/mol, respectively) after acclimation for 5 weeks. 5. In summary, it appears that after appropriate in vivo acclimation, channel catfish T cells are better able to cap mAg at low assay temperatures than are B cells. These results suggest that mAg capping is not the low temperature sensitive step involved in T cell immunosuppression in channel catfish. PMID- 2900094 TI - The protein content of extracellular fluids and its relevance to the study of ionic regulation: net charge and colloid osmotic pressure. AB - 1. Protein net charge in blood plasma and haemolymph is relevant to overall anion cation balance, Donnan equilibria, colloid osmotic pressures (COPs), buffering and liquid junction potentials, but its definition and measurement are not always straightforward. 2. Normal values of protein net charge in man and other animals are discussed, as is their dependence on pH. 3. Although it is clear that charge on a protein augments COP, the theory of COP is still incomplete. 4. The dependence of COP on protein and salt concentrations and on pH are therefore considered empirically. 5. Normal values for COP in various animals are given and the regulation of COP is discussed. PMID- 2900095 TI - Haematology and iron status of the Egyptian fruit bat, Rousettus aegyptiacus. AB - 1. Haematological values and iron status of wild and captive fruit bats (Rousettus aegyptiacus) were determined. 2. Plasma iron concentrations were 175 micrograms/dl in wild males, and 286-316 micrograms/dl in captive bats. 3. Total splenic stores were small (around 100 micrograms) in relation to hepatic stores (3 mg) and total haem iron (2.6 mg). 4. Haemoglobin levels, red cell counts and haematocrits were unusually high and mean corpuscular volumes low. 5. Lactating wild bats showed no deficits in iron status or in haematological values. 6. It is concluded that the ascorbic acid content of fruit, together with the bats' high food requirement, has ensured an ample iron supply in this vegetarian species. PMID- 2900096 TI - Studies on renal excretion of potassium in the dik-dik antelope. AB - 1. In a study on the renal handling of potassium by the dik-dik antelope, plasma and urine samples were analysed for potassium, sodium and creatinine concentrations and osmolality during dehydration and intra-ruminal loading of potassium solutions. 2. The fractional excretion of potassium was 0.64 during the control period and rose up to as high as 2.3 during potassium loading. Urinary osmolality and potassium concentration decreased as the urine volume increased but the total amounts of potassium excreted were independent of urine volume. 3. Potassium loading led to a steady increase in its urinary excretion but a decrease in plasma potassium concentration was observed. This observation casts doubt on the hypothesis that alterations in potassium intake produce parallel alterations in plasma potassium concentration (which supposedly stimulates or depresses potassium excretion) and thereby maintain potassium homeostasis. 4. A possible alternative signal for increased potassium excretion following increased intake is discussed. PMID- 2900097 TI - Plasma cathepsin activity and the role of hypovolemic shock in dehydrational death in the toad, Bufo marinus. AB - 1. The pH- and activator-dependence of toad plasma cathepsin activity assayed by hemoglobin digestion was characteristic of cathepsins B1 and D. 2. Dehydration, even to the point of death, did not produce a significant elevation of plasma cathepsin activity over controls. 3. Toads were remarkably resistant to the effects of splanchnic artery ligation, which also did not produce significantly higher plasma cathepsin levels. 4. Cardiac depression via the production of a myocardial depressant factor by cathepsins does not appear to be an important factor in dehydrational death in toads. PMID- 2900098 TI - Consumption of blood, renal function and utilization of free water by the vampire bat, Desmodus rotundus. AB - 1. Captive vampires consume blood to an average of 59.5% of their body weight in a period no longer than 30 min. 2. Fluid consumption by the vampire is mainly dependent on the presence of plasma in fluid. 3. Ingestion of blood is accompanied and followed by diuresis, urine flow attained a peak 20-25 min after feeding. 4. Urine osmolality increased with time after feeding. Vampires concentrate urea in urine to 2630 mmol/l but cannot concentrate electrolytes beyond 453 mmol/l. 5. Inorganic salts other than sodium chloride never contribute more than 9% to the total osmotic activity. 6. Na to Cl ratio and concentration of non-nitrogenous organic acids increase with urine osmolality. 7. Vampires drink free water if available. PMID- 2900099 TI - Spectral sensitivity of melanophores of a freshwater teleost, Zacco temmincki. AB - 1. The melanophores of a freshwater teleost, Zacco temmincki, responded to changes in illumination: in darkness the melanophores induced a melanosome aggregation and when subjected to light they caused a melanosome dispersion. 2. Using monochromatic light, the spectral sensitivity of the melanophores was examined. 3. The melanophores showed a different sensitivity to light between 400 and 600 nm with a maximum at about 525 nm. 4. The action spectrum closely resembled a porphyropsin absorbance curve, suggesting a porphyropsin or similar photopigment is active in the melanophore light response of Zacco temmincki. PMID- 2900101 TI - A comparison of postnatal thermal physiology and energetics in an altricial (Gerbillus perpallidus) and a precocial (Acomys cahirinus) rodent species. AB - 1. Daily weight increase is polyphasic in Gerbillus perpallidus whereas it follows a linear pattern in Acomys cahirinus. 2. Young A. cahirinus achieve full homeothermic capacities much earlier (less than or equal to 12 days old) than G. perpallidus (19-21 days old). 3. The differences in the development of the two species are reflected in the alterations of their metabolic rates. 4. In both species, age-dependent phases of development are obvious, beginning, however, much later in G. perpallidus. 5. It is concluded that, by postponing functional maturity, considerably more energy can be allocated to growth. This may be a precondition for the altricial mode of development. PMID- 2900100 TI - Metabolic rate of feeding and fasting juvenile midland painted turtles, Chrysemys picta marginata. AB - 1. Resting metabolic rates at 25 degrees C were determined for juvenile midland painted turtles that had recently been fed or fasted for 1, 2, 4, 6, 10, 14 or 19 days. 2. Recently fed turtles had an oxygen consumption rate of 211 microliter O2/g/hr. This decreased by 32% on the first day of the fast and by 69% by the 19th day. 3. Mass of the turtles (4.91-14.30 g) did not affect the rate of oxygen consumption (VO2). PMID- 2900102 TI - Hormonal regulation of preputial gland function in male Microtus montanus, the montane vole. AB - 1. Preputial gland function in male Microtus montanus is androgen-dependent, both in terms of preputial weights and in the production of a series of lipids which are present in M. montanus and absent from Microtus pennsylvanicus. 2. Production of these species-typical lipids is decreased but not eliminated in castrates, as well as in adrenalectomized castrates treated with corticosterone. Therefore, in the total absence of androgens, a low level of these lipids is still produced. 3. 5 alpha-dihydrotestosterone and 17 beta-estradiol enanthate have limited effects on maintenance of preputial weight, suggesting that testosterone itself is the active steroid in the preputial gland of this species. PMID- 2900103 TI - Digestion, assimilation and metabolism of captive estuarine crocodiles, Crocodylus porosus. AB - 1. Digestion, assimilation and metabolism of lean and fatty pork were studied in immature C. porosus. 2. Up to 92% of protein was digested but protein digestion was adversely affected by high levels of dietary fat. 3. Protein was catabolized in preference to fat, much of which was stored, although the ratio between metabolizable energy and protein retention was still 2.73 g/100 kJ. 4. 56.8% of ingested energy was stored, maintenance requirements taking as little as 7.7%. 5. Up to 13.8% energy was spent digesting and assimilating food. PMID- 2900104 TI - Thyroid function in a lizard, a tortoise and a crocodile, compared with mammals. AB - 1. Thyroid activity was examined in the lizard, Trachydosaurus rugosus, the tortoise Chelodina longicollis and the crocodile, Crocodylus johnstoni, acclimated to 20-22 degrees C and 30-32 degrees C. Thyroidal uptake and release of 125I, plasma concentrations of T3 and T4 were measured as was resting oxygen consumption (at 30 degrees C) before and after both thyroidectomy and thyroxine injections. 2. All three species showed 125I uptake at both temperatures and showed no thyroidal release of 125I at 20-22 degrees C but exhibited thyroidal release of 125I (and presumably hormone secretion) at 30-32 degrees C. 3. Plasma concentrations of thyroxine ranged from 0.55 nM to 3.24 nM and triiodothyronine from 0.14 nM to 0.51 nM. 4. Neither thyroidectomy nor thyroxine injections had any effect on metabolic rate in 20-22 degrees C acclimated lizards. Thyroidectomy resulted in a significant decrease in metabolic rate in 30-32 degrees C acclimated lizards and tortoises and thyroxine injections resulted in significant increases in metabolism in 30-32 degrees C acclimated lizards, tortoises and crocodiles. 5. A comparison of thyroid parameters in reptiles and mammals concluded that although the reptilian thyroid is active at high temperatures it is still considerably less active than it is in mammals. PMID- 2900105 TI - Chemical composition of blood and seminal plasma of Barbus aeneus (Cyprinidae). AB - 1. The chemical composition of the seminal and blood plasma of Barbus aeneus (smallmouth yellowfish) were determined. 2. Various concentration differences between the components of the seminal and blood plasma were noted. 3. Differences found can be ascribed to the existence of a blood-testis barrier. PMID- 2900106 TI - Possible evolutionary futures for mankind. AB - 1. With the development of techniques of gene transfer, human genetic defects such as sickle cell anaemia, phenylketonurea, cystic fibrosis, haemophilia, Huntington's chorea, etc. will be eliminated. Ninety nine percent of humans in the year 2500 will be much the same as at present, but healthier. 2. Studies of Comparative Biochemistry and Physiology show that many strategies have been developed in the Animal Kingdom that could be advantageous in furthering human survival. Some of these strategies are discussed in the present article. 3. Commensal algae that will live in the epidermis of domestic animals (pigs, goats, cattle) will be developed enabling these animals to live in dry environments with minimal demands for food and water. Once successful in domestic animals, the algae could be adapted to live in some humans, i.e. the "Green Man". 4. Commensal protozoa and bacteria that digest cellulose and lignin will be developed so that they can live in the human gut and convert the material to sugars, volatile fatty acids and amino acids that can be absorbed and metabolized by Man, thus making many inexpensive vegetable food resources available. 5. Mammalian embryos will be able to develop through to full term in vitro in a cleidoic egg; and the in vitro fertilized egg will have to depend on finding a surrogate mother. 6. Some people will have an altered pattern of sexual activity. Many patterns will be available; one suggested here is of protogynous hermaphroditism, i.e. the individuals would be female for the first 30 years of life and male for the remaining years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900107 TI - Cardiovascular correlates of exercise in snapping turtles, Chelydra serpentina. AB - 1. Heart rate increased with a rise in body temperature (10-30 degrees C) and with induced physical exercise in snapping turtles. 2. Maximum heart rate increment occurred at 30 degrees C. 3. Standard oxygen pulse did not change with a rise in temperature. 4. Oxygen pulse during exercise and oxygen pulse increment were maximal at 10 degrees C and minimal at 20 degrees C. 5. The increase in heart rate with exercise accounted for only 9-22% of the increase in oxygen transport during activity; the remainder was provided by a rise in cardiac stroke volume and/or A-V difference. PMID- 2900108 TI - Orientation responses of American eels, Anguilla rostrata, to varying magnetic fields. AB - 1. The locations of freshwater yellow eels in an eight-chambered octagonal behavior tank were videotaped during six-day intervals while the animals were being subjected to normal and experimental magnetic fields. 2. The earth's magnetic field (0.5 g) was utilized for two control periods at the start and completion of each run for each animal. 3. During each run, the sequence of applied magnetic fields was +1.0, 0.0, -0.5 and -1.0 g, each being applied for a period of 24 hr. 4. Under the influence of the earth's magnetic field, the eels showed a preference for a northeast direction (27.01%). During the second control period (i.e. after being subjected to variations in the magnetic field), the animals showed a dual preference for north and northwest directions (23.02% and 25.9%, respectively). 5. In a 0.0 g field, the eels preferred the north chamber (24.43%) and the vestibule of the behavior tank (19.46%); a preference for north was also obtained with a field of +1.0 g (25.95%). 6. The preferred direction with the -0.5 and -1.0 g fields was southeast (20.93 and 26.71%, respectively). PMID- 2900109 TI - Nonfaecal and faecal losses of Pomadasys commersonni (Teleostei: Pomadasyidae) feeding on the surf clam, Donax serra. AB - 1. The nonfaecal and the faecal production of Pomadasys commersonni, a marine teleost, were investigated at 15, 20 and 25 degrees C. 2. Nonfaecal nitrogen excreted by starved and fed P. commersonni consisted mainly of ammonia-N. 3. The mass component b of the equation, AE = aMb (AE, ammonia-N in Mg-N/hr; M, fish mass in g) ranged from 0.68-0.72 and 0.71-0.75 for starved and fed fish, respectively, and was temperature-independent. 4. The mean percentage of the food energy lost as nonfaecal energy (exogenous plus endogenous) was 4.38 +/- 2.68%. 5. The faeces had a low energy content and ranged from 2.09 to 4.25 kJ/g. 6. Assimilation efficiencies showed some variation and ranged from 7.34 to 99.34% for dry matter and from 96.02 to 99.89% for energy. 7. The mean combined energy loss was 11.77% of the ingested energy. PMID- 2900110 TI - Nonfaecal and faecal losses of the marine teleost, Lichia amia (Linnaeus, 1758), feeding on live southern mullet, Liza richardsonii (Smith, 1846). AB - 1. Nonfaecal and faecal losses of Lichia amia were determined under controlled laboratory conditions at 15, 20 and 25 degrees C. 2. Ammonia-N was the major form of nonfaceal nitrogen excreted by L. amia and excretion rates were temperature dependent. 3. The mass component b of the mass/ammonia-N excretion equation was temperature-independent and ranged from 0.63-0.65 and from 0.66-0.73 for starved and fed fish, respectively. 4. Mean nonfaecal energy loss (exogenous plus endogenous) was 3.78 +/- 1.99% of the ingested energy. 5. Assimilation efficiencies varied between individual fish and ranged from 61.24-93.79% (mean 80.76 +/- 7.14%) for dry matter and 87.52-98.22% (mean 94.09 +/- 2.22%) for energy. 6. The mean nonfaecal and faecal energy loss was 23.11 +/- 1.67% of the ingested energy. PMID- 2900111 TI - Physiology of chemoreceptor cells in the legs of the freshwater prawn, Macrobrachium rosenbergii. AB - 1. Chemoreceptor cells in the first pereiopods (legs) of the freshwater prawn, Macrobrachium rosenbergii, were investigated using single-unit, extracellular electrophysiological recording techniques on an isolated, perfused leg preparation. 2. The cells were responsive to aqueous extracts of food (shrimp, mullet, trout chow), a salt mixture (artificial sea-water), amino acids (L arginine HCl, taurine), a quaternary ammonium compound (betaine HCl) and ammonium chloride. 3. The response specificity of individual cells ranged from narrow to broad, but on average was broad, being more similar to chemoreceptor cells of freshwater crayfish than of marine spiny or clawed lobsters. 4. Responses were generally excitatory. However, some responses were inhibitory, the first such demonstration in aquatic crustaceans. 5. These electrophysiological results highly correlate with results of feeding behavioral assays carried out on M. rosenbergii. PMID- 2900112 TI - Water balance during saline imbibition in the Mongolian gerbil (Meriones unguiculatus). AB - 1. There were few changes in the water balance of gerbils drinking 0.25 and 0.50 M NaCl solutions for 5 days. 2. Imbibition of 0.75 and 1.0 M saline resulted in some dehydration of the body fluids and considerable depletion of the neural lobe vasopressin store. 3. Although large amounts of NaCl were excreted, the maximum urine osmolality was considerably less than that found following water deprivation. 4. The imbibition of 1.0 M saline caused similar changes in water balance to water deprivation showing that little, if any, water was gained from this solution. PMID- 2900113 TI - Cooling rates of living and killed chicken and quail eggs in air and in helium oxygen gas mixture. AB - 1. In a helium atmosphere, heat is dissipated from a surface 3.5 times faster than it is in air. Eggs in a helium-oxygen atmosphere cool only 1.4 times faster than they cool in air. This signifies that internal resistance to heat flow is a significant factor in the cooling rates of eggs. 2. Heat flow occurs inside an egg in two ways: by conduction through the tissues and in flowing blood. Killing an embryo stops the latter, but not the former. Eggs cool more slowly after they have been killed, signifying that blood flow can be an important component in an egg's internal flows of heat. 3. Blood flow should be a relatively more important component of heat flow in large eggs than in small eggs. The difference in conductance between living and killed eggs is larger in 60 g chicken eggs than it is in 10 g quail eggs. PMID- 2900114 TI - The evolutionary origin of eukaryotic transmembrane signal transduction. AB - 1. A comparison was made of transmembrane signal transduction mechanisms in different eukaryotes and prokaryotes. 2. Much attention was given to eukaryotic microbes and their signal transduction mechanisms, since these organisms are intermediate in complexity between animals, plants and bacteria. 3. Signal transduction mechanisms in eukaryotic microbes, however, do not appear to be intermediate between those in animals, plants and bacteria, but show features characteristic of the higher eukaryotes. 4. These similarities include the regulation of receptor function, adenylate cyclase activity, the presence of a phosphatidylinositol cycle and of GTP-binding regulatory proteins. 5. It is proposed that the signal transduction systems known to operate in present-day eukaryotes evolved in the earliest eukaryotic cells. PMID- 2900116 TI - Glycosylated haemoglobin: an indicator of long-term blood glucose in domestic sheep and goats. AB - 1. Percentages of glycosylated Hb were determined in (32) Najidi sheep (Ovis ovies) and (20) Nubian goats (Capra hiscas) from Saudi Arabia, using the thiobarbituric acid (TBA) method. 2. The levels of glycosylated Hb in sheep (3.24%) and in goats (3.96%) differ significantly from human controls (4.9%) (P greater than 0.001). 3. Generally, low blood glucose and shorter erythrocyte life span in sheep and relatively in goats are reflected in a lower value for glycosylated Hb, indicating that glycosylated Hb may be used as a valid index of long-term mean blood glucose in sheep and goats. PMID- 2900115 TI - Some effects of water deprivation on dorcas gazelle (Gazella dorcas) in the Sudan. AB - 1. The effects of dehydration for 10 days and subsequent rehydration for 2 days on some physiological and biochemical parameters were studied in the Dorcas gazelle. 2. At the end of the 10 days of dehydration, feed intake and body weight were decreased by 42 and 29% of the control values, respectively. Rehydration restored most of the loss in feed intake and body weight. 3. Dehydration decreased the water content in the faeces of the gazelles by 41%. Rehydration restored 36% of the lost faecal water. Urine volume in dehydrated animals decreased by 66%, an effect which was readily reversed by rehydration. 4. Blood haemoglobin of dehydrated gazelles decreased by 22% but this effect was not reversed by rehydration for 2 days. 5. Dehydration for 10 days decreased the concentration of serum glucose by 34% and increased that of urea and albumin by 34 and 18%, respectively. Dehydration for 2 days reversed these effects completely. 6. The serum concentrations of sodium, potassium and chloride were increased by dehydration by 23, 44 and 18% respectively. After 2 days of rehydration the values returned to normal. 7. No change in the heart rate, pulse or temperature was found during the dehydration period. 8. The gazelles survived the 10 days of dehydration, although they tended to be drowsy, weak and emaciated during the last 2 days of dehydration. The animals appeared normal after rehydration. PMID- 2900117 TI - The intestinal epithelial cells of ground squirrel (Citellus undulatus) accumulate at G2 phase of the cell cycle throughout a bout of hibernation. AB - 1. The mitotic index was found to be greatly reduced in the intestinal crypt cells of ground squirrel during bout of hibernation. The percentage of mitosis rose abruptly at least 2 hr after arousal. 2. An increase in the number of G2 cells was found in the intestinal tract of ground squirrel during bouts of hibernation. 3. The conclusion can be drawn that the cells are progressing steadily through the cell cycle. The cells accumulate at G2 in hibernation. 4. It was assumed that the block in G2 prevents the cells from possible damage in mitosis under hypothermia accompanying hibernation and, therefore, it represents an adaptive reaction. PMID- 2900118 TI - The Arabian race camel normal parameters--I. Haemogram, enzymes and minerals. AB - 1. Racing camels' (Camelus dromedarius) normal blood parameters were determined in Al-Ain, U.A.E. The parameters were: packed cell volume, haemoglobin, total red and white blood cells, the activities of glutamate oxaloacetate (GOT), creatinine kinase (CK), gamma-glutamyl transferase (gamma-GT) and CK muscle-brain isoenzyme and the concentrations of creatinine, urea, total protein, albumin, calcium, magnesium, phosphorus, sodium, potassium, zinc, copper and iron. 2. Most blood parameters were found to differ from those of other domestic animals and from non race camels. 3. The data are discussed in relation to the management system practised. PMID- 2900119 TI - Developmental study of digestive motor response to dietary pattern in young broilers. AB - 1. Gastrointestinal (GI) morphometry and motility were measured in young broilers (3, 8 and 15 days old) when they were submitted to three dietary patterns (ad libitum food, acute 48-hr fast and cumulative semi-starvation). 2. All GI regions were hypertrophied when acute or intermittent starvation were applied; lightly when acute starvation was applied and strongly with intermittent starvation. 3. All the 3-, 8- and 15-day-old acutely and intermittently starved chickens increased GI motility at the shortest times (0.5 and 1 hr) after the marker administration, but decreased GI motility at the longest times (2 and 4 hr). 4. The GI motor response of intermittently starved chicks was faster than the observed one in acutely starved chicks. The GI tract of intermittent starved chicks increased its motor response proportionally to the broilers age, while acutely starved chicks decreased their GI motility when the broilers age was increased. 5. A relationship between morphometrical and motor GI responses to dietary pattern has been inferred. From the gizzard and small bowel hypertrophy caused by intermittent starvation, an increased reflex GI motor response can be expected. Acute starvation only caused a light increase of GI motility, because it only increased the gizzard morphometry. 6. We concluded that young chicks respond to acute starvation by means of a short-term mechanism (an increase of GI motor reflexes) and responds to intermittent starvation by means of a medium- and long-term mechanism (a hypertrophy of GI tract and its subsequent increase of GI motor reflexes). PMID- 2900120 TI - Drinking induced by cellular dehydration in the quail, Coturnix coturnix japonica. AB - 1. Drinking was induced in water-replete quail 5-10 min after intravenous injection of hypertonic NaCl (0.69 osmol/l) or sucrose (1.06 osmol/l), but hypertonic urea (2.78 osmol/l) failed to induce drinking. 2. The birds drank approximately the amount required to dilute the injected solutes to isotonicity for each given dose of NaCl or sucrose. 3. The plasma angiotensin II level decreased after injection of 7% NaCl (2.5 osmol/l), but it increased after injection of an equi-osmolar solution of sucrose (65%). 4. Plasma osmolality and Na+ concentration returned quickly to control levels, and then decreased further, after injection of 7% NaCl or 65% sucrose. 5. Blood volume and blood pressure increased immediately after injection of 7% NaCl or 65% sucrose. 6. These results show that drinking is induced after injection of hypertonic solutions exclusively by cellular dehydration, and other regulatory mechanisms for thirst, such as extracellular dehydration and the renin-angiotensin system, are rather inhibitory after injection of hypertonic NaCl. PMID- 2900121 TI - Plasma levels of beta-endorphin in white-tailed deer: seasonal variation and the effect of thyroxine, GnRH, dexamethasone and ACTH administration. AB - 1. A distinct seasonal cycle of beta-endorphin (beta-E) was detected in plasma of four intact, male white-tailed deer. Peak levels (around 11 pg/ml) were observed in August and minimal concentrations (around 5 pg/ml) were detected in January and February. 2. The seasonal variation (which corresponds to intensity of antler growth) was more pronounced in the two mature bucks, as compared to the immature ones. 3. Intramuscular administration of synthetic thyroxine (in doses of 500, 750 and 1000 micrograms/deer) and GnRH (100 micrograms/deer) had generally no significant effect on the beta-E levels. 4. I.v. administration of dexamethasone (5 mg/deer) as well as i.m. injection ACTH (20 Int. Units/deer) significantly reduced beta-E levels. PMID- 2900122 TI - Biliary and pancreatic exocrine secretions via endogenous secretin by intestinal infusion of propionate and propionate analogues in piglets. AB - 1. The secretory responses of hepatic bile and exocrine pancreas by intraduodenal infusion of propionate (PA), 3Cl-PA, 2Cl-PA, 3Br-PA and 2Br-PA solutions were examined in anesthetized piglets. 2. Pancreatic juice and protein secretions were enhanced by infusion of PA and PA analogue solutions of pH 2.0 following increase of plasma secretin level but not pH 7.0. The order of response time was as follows: 3Br-PA greater than 2Cl-PA greater than 2Br-PA greater than 3Cl-PA greater than PA. 3. The response of bile flow depended on endogenous secretin and showed almost the same pattern as that of pancreatic juice secretion. 4. The results suggested that pancreatic exocrine secretion via endogenous secretin was not always dependent on the dissociation constant of weak acids. PMID- 2900123 TI - Changes in plasma thyroid hormones, luteinizing hormone (LH), estradiol, progesterone and corticosterone of laying hens during a forced molt. AB - 1. Circulating concentrations of iodothyronines, luteinizing hormone(LH), estradiol(E2), progesterone and corticosterone were measured in hens before, during, and after a forced molt induced by fasting. 2. Corticosterone increased at the onset of molt, peaked at the maximal molt and returned to pre- and post molt levels. LH, E2 and progesterone declined during the molt, and the decline was coincident with the cessation of egg production. 3. Thyroxine(T4), triiodothyronine (T3) and reverse triiodothyronine(rT3) increased during the molt. The increases of T4 and T3 were not abolished even if the forced molt was conducted in mild weather. PMID- 2900125 TI - The effect of hypoglycemic sulfonylureas on human red blood cell transglutaminase activity. AB - We have examined the effect of glipizide, a hypoglycemic sulfonylurea, upon transglutaminase activity in human red blood cells. In a first series of experiments the in vitro effect of the drug was assessed. The results obtained showed that glipizide inhibits transglutaminase activity in human red blood cells. In a second approach, glipizide was administered orally to six type 2 diabetic patients during 3 months, in order to evaluate the long-term effect upon transglutaminase activity. Again, glipizide induced a significant decrease in the enzyme activity in blood red cells (P less than 0.01). We suggest that treatment of type 2 diabetes mellitus with hypoglycemic sulfonylureas could improve insulin effects by inhibiting cellular transglutaminase activity. PMID- 2900124 TI - The effect of beta-blocker on ERG c-wave of the rabbit. AB - The toxicity of beta-blocker, Befunolol HCl (BFE), to the retinal pigment epithelium was investigated electrophysiologically. Rabbit in vivo ERG b- and c waves were recorded after intravitreal injections of 0.1 ml of 0.25, 1, 2, 4, 6 and 10% BFE solutions with osmolalities of 304, 340, 383, 432, 493 and 618 mOsm respectively. Phosphate solutions with osmotic pressure corresponding to the BFE solutions were injected as control. In eyes injected with 0.25% BFE, amplitude of either b- and c-waves were unchanged for 60 min, while in eyes injected with BFE with a higher concentration than 1%, the b-waves attenuated but the c-waves enhanced in proportion to the BFE concentrations. In the control group, the b waves attenuated and the c-waves enhanced by the injection of the high osmotic phosphate solutions up to 500 mOsm, which corresponded to the osmotic pressure of 6% BFE, but attenuated by the phosphate solutions higher than 600 mOsm. Based on the above result, no acute toxicity of BFE to the retina was suggested in dose of its therapeutic use. The attenuation of b-waves by BFE was likely due to the influence of osmotic pressure since no significant difference in the b-waves amplitudes was found between BFE and equimolar phosphate solutions. However, high concentration of BFE itself was suggested to exhibit an effect to enhance the c wave because a manifest difference was observed in the c-wave amplitudes between the group at higher BFE concentrations and the correspond control group. PMID- 2900126 TI - [Murine radiation chimeras with mosaic hematopoietic tissue from several species of rodent]. PMID- 2900127 TI - [Drug-induced alveolitis caused by salazosulfapyridine]. AB - At onset of chronic rheumatoid arthritis a 36-year-old woman was started on a course of sulphasalazine. During the first four weeks the treatment she developed severe dyspnoea, mild fever, dry cough with chest pain, marked hypoxaemia and severely abnormal restrictive lung functions. Chest x-ray demonstrated diffuse alveolar-interstitial infiltrates. After discontinuing the drug and short-term administration of corticosteroids, blood gases and the chest x-ray reverted to normal within four weeks, but the abnormal lung functions persisted. The course of the illness and published reports on the side effects of sulphasalazine point to the need of carefully watching out for possible side effects during the first three months of treatment with this drug. PMID- 2900128 TI - Cytological effects of khat (Catha edulis) in somatic and male germ cells of mice. AB - Cytological effects of khat (Catha edulis), a popular drug of abuse from Southern Arabia and Eastern Africa, have been studied in Swiss albino mice. The studies on the somatic system involved the use of micronucleus test and the cytological analysis of the mitotic index in the femoral cells of mice. In the micronucleus test, the mice were treated with different doses of khat extract (125, 250 and 500 mg/kg, p.o.) 30 and 6 hours before sacrificing the animals. The polychromatic erythrocytes were screened for the induction of micronuclei. For the analysis of bone marrow cytotoxicity, the mice were treated with the dose of 125, 250 and 500 mg/kg, body weight, p.o. daily for 5 consecutive days. The animals were sacrificed and the femoral cells were microscopically examined for the mitoses. Following the same schedule of treatment, studies on the cytogenetic analysis of meiotic chromosomal aberrations and the sperm head abnormality were undertaken. Khat extract significantly increased the frequency of micronucleated polychromatic erythrocytes, induced bone marrow depression and reduced the mitotic index of the somatic cells. It induced significant chromosomal aberrations viz., aneuploids, autosomal univalents, univalents of the sex chromosomes and polyploids. The frequency of abnormal sperms was also increased. PMID- 2900129 TI - Experimental studies on the neurocardiovascular effects of urapidil. AB - The major purpose of our study was to determine whether urapidil acts in the central nervous system (CNS) to lower arterial blood pressure. Once demonstrating a CNS antihypertensive action of urapidil we further set out to determine: (1) the relative role of a CNS antihypertensive action to the total antihypertensive effect of urapidil; (2) the brain site of action for the antihypertensive effect of urapidil; and, (3) the receptor mechanism whereby urapidil acts in the CNS to lower arterial blood pressure. Studies were conducted in chloralose-anaesthetised cats, and arterial blood pressure and heart rate were monitored. Drugs were administered intravenously (IV), into the cerebral ventricles (ICV), topically by application to the ventral surface of the medulla and by microinjection into specific nuclei. Receptor binding studies were also conducted using rat cerebral cortex homogenates. We found that injection of urapidil into the fourth ventricle decreased arterial pressure. Local application of urapidil to the ventral medullary surface also decreased arterial blood pressure. Microinjection of urapidil into one of the nuclei associated with the ventral surface of the medulla, the rostral part of the nucleus reticularis lateralis (rLRN), produced a similar degree of antihypertensive effect. The effect of urapidil was not altered by alpha 1-receptor blockade. Instead, the urapidil effect resembled that produced by drugs that stimulate serotonin (5-hydroxytryptamine)-1A receptors (B695-40 and 8-OH-DPAT). Furthermore, urapidil was found to have the highest potency for binding to serotonin-1A receptor sites (as compared to alpha 1- and alpha 2-receptor sites). Urapidil administered IV was shown to lower arterial blood pressure in part by blocking peripheral alpha 1-adrenoceptors but also, in high doses, by acting in the CNS to decrease central sympathetic outflow. These data indicate that urapidil is a unique drug, possessing both peripheral and CNS actions which contribute to its antihypertensive effect. Urapidil may also be unique in that its central action may involve activation of serotonin-1A receptors. PMID- 2900130 TI - Effects of alpha-adrenoceptor blockers on renal function and blood pressure adjustment in human hypertension. AB - In this paper the different aspects of the role played by alpha-adrenoceptors in the control of renin secretion from the juxtaglomerular apparatus and renal sodium and water reabsorption, and the effects of alpha-adrenoceptor antagonists on systemic haemodynamics, will be investigated. Animal experiments suggest that the renal alpha-adrenoceptors exert a restraining action on renin secretion while increasing tubular reabsorption of sodium and water. A recent study in man has confirmed the alpha-adrenoceptor-mediated inhibition of renin secretion. Previously available ganglion blocking and antiadrenergic agents, while causing a significant supine blood pressure reduction, can cause at the same time clinically relevant side effects such as orthostatic hypotension, sedation, drowsiness etc. The advent of selective alpha 1-adrenoceptor blockers, such as prazosin and urapidil, allow a significant blood pressure reduction without significant interference on haemodynamic adjustments and only induce a limited incidence of side effects. PMID- 2900131 TI - Systemic and regional haemodynamic profile of diuretics and alpha- and beta blockers. A review comparing acute and chronic effects. AB - The influence of the acute and chronic administration of antihypertensive agents on blood flow to various organs which are known targets of hypertension is important in the determination of drug therapy for this disorder. In association with the frequently observed fall in cardiac output and increase in total peripheral resistance in response to acute administration, beta-blockers may induce a decrease in blood flow to the brain and kidney. However, during chronic treatment it has been widely shown that total peripheral resistance returns to pretreatment levels (except for labetalol, a beta-blocker with alpha-blocking properties) whilst renal and cerebral blood flows are unaffected. Although alpha blockers acutely lower blood pressure and induce a baroreflex-mediated increase in heart rate and cardiac output while not affecting cerebral blood flow, during chronic treatment no change in systemic or cerebral or renal blood flow is observed. Diuretics and dietary sodium restriction, which are the most widely used therapeutic interventions, are usually well tolerated; however, in aged patients in whom renal adaptation to sodium depletion is impaired, deterioration of renal function may be observed. PMID- 2900132 TI - Renal haemodynamic and neurohumoral responses to urapidil in hypertensive man. AB - In order to evaluate the acute effects of urapidil on renal vascular tone and on pressor systems we performed a randomised placebo-controlled crossover study in 8 patients with uncomplicated essential hypertension. Each subject received, on two separate days one week apart, an intravenous injection of either placebo or urapidil (25 mg, to be increased to 50 mg if blood pressure did not fall within 5 minutes). Before and following this injection we measured blood pressure and heart rate (Dinamap), renal plasma flow (125I-hippuran), renin, angiotensin II, aldosterone, and catecholamines. The results show that urapidil, when compared to placebo, significantly reduced blood pressure, while increasing heart rate, renal blood flow, noradrenaline and adrenaline. Dopamine levels, on the other hand, were suppressed. While renin and angiotensin II were only mildly stimulated, aldosterone levels increased markedly. It is concluded that urapidil, given intravenously, has an immediate blood pressure lowering effect associated with a fall in renal vascular tone and an increase in renal perfusion. As a consequence both the sympathetic system and the renin-angiotensin system are stimulated, although the latter only to a mild degree. The rise in aldosterone may be related to withdrawal of dopaminergic tone. PMID- 2900133 TI - [Therapeutic indications of S-adenosyl methionine in neuropsychiatry]. AB - Studies conducted by Italian and Anglo-saxon authors underline the thymoanaleptic properties of a transmethylant biological substance, the S-adenosyl methionine (SAMe). The authors discuss a review of literature concerning the use of SAMe in neuro-psychiatry, particularly in the treatment of affective disorders. The many physiopathological implications are subtended by the biological inter-relations of SAMe with other biological substances. Some hypotheses are proposed on the role played by phospholipid methylation, the folate metabolism and the purinergic transmission in mental diseases. PMID- 2900134 TI - [Medicolegal aspects of tardive dyskinesia in the United States]. AB - Tardive dyskinesia is by definition a neurological complication resulting from neuroleptic treatment. The exact role of neuroleptic drugs in the etiopathogenicity of this syndrome is discussed. The manifestation of dyskinesia in a patient who is under neuroleptics may involve the responsibility of a physician. The evolution of jurisprudence in the United States is analysed. PMID- 2900135 TI - Combined effects of human growth hormone (GH)-releasing factor-44 (GRF) and somatostatin (SRIF) on post-SRIF rebound release of GH and prolactin: a model for GRF-SRIF modulation of secretion. AB - Somatostatin (SRIF) and GRFs play key roles in regulating GH secretion. We previously presented a model of SRIF-cAMP interaction; SRIF blocks rat (r) GH release without preventing its accumulation in a potentially releasable pool. This phenomenon may represent a mechanism whereby tonic SRIF inhibition and its subsequent reduction or withdrawal can modulate the magnitude if not the initiation of rGH pulses. Herein we test that model using human GRF-44 (hGRF-44). Tritium-prelabeled rat anterior pituitary fragments were perifused until stored [3H]rGH and [3H]rPRL release rates were stable. SRIF (10 or 25 nM), with and without hGRF-44 (3 or 10 nM), was added in short (1-h hGRF-44) and long (3-h hGRF 44) protocols; SRIF was then withdrawn while hGRF-44 was continued. Release of stored prelabeled [3H]rGH and [3H]rPRL was assessed by immunoprecipitation. Effects on PRL release were followed for comparison. SRIF-induced inhibition of release was only partially reversed by hGRF-44. At these concentrations and so long as SRIF was present, hGRF-44 could not stimulate the rate of hormone release to values above pre-SRIF basal rates. On the other hand, the amplitude of post SRIF rebound release was increased by prolonging exposure to SRIF alone, by including hGRF-44 with SRIF, by increasing the amount of hGRF-44 included with SRIF, by prolonging exposure to hGRF-44 plus SRIF, and by using a smaller concentration of SRIF during exposure to hGRF-44. Interaction of hGRF-44-SRIF effects generated peak rates of hormone release after SRIF withdrawal which exceeded the maximum rates achieved using hGRF-44 alone in this system. Lactotroph responses were much smaller, but qualitatively resembled somatotroph responses. We conclude that the interplay of simultaneous hGRF-44 and SRIF effects can regulate the amplitude of rGH pulses. Although GRF can initiate physiological GH release, and GRF antisera can block GH pulses, we suggest that the surge of release that follows reduction of SRIF-induced inhibitory tone in vitro represents a potential mechanism that could contribute to the initiation of some pulses of release. Finally, we also present a theoretical model of secretagogue interactions at the cellular level to explain our results. The model is compatible with either a homogeneous cell population in which each secretory cell has multiple capabilities or a heterogeneous cell population composed of cell subgroups with complementary secretory abilities. PMID- 2900136 TI - The nonhuman primate as a model of growth hormone physiology in the human being. AB - Our review confirms the close correlation of the physiology of GH secretion in the nonhuman primate and the human subject which has not been seen in any other animal model, at least from the studies available to date. Except for a discrepancy in the relationship of GH secretion during early sleep, there are no significant differences between the species that can not likely be explained by methodological differences. Even the discrepancy between nighttime GH secretion may be due to methods of studying the nonhuman subjects. But methodological problems are at the heart of the problem in primate research. Primates are expensive to buy ($800-$1200 is not unusual for an adult male), expensive to house ($2-$3 per day is customary), dangerous to work with (bodily injury and serious infections are equally worrisome to handlers), exquisitely sensitive to environmental factors (as noted above), and above all, the subject of appropriate concern from animal use committees: these factors easily explain the relative dearth of primate studies on GH physiology compared to rodent studies. Problems of handling the animals and ensuring their stable state are helped to large degree by facilities such as the Regional Primate Facilities in the United States. The studies reviewed above should clearly demonstrate that the primate model, in spite of all the difficulties involved, is invaluable in investigating physiological phenomenon impossible to pursue in the human being. But only studies offering fastidious attention to detail in this potentially unstable model of GH physiology are likely to answer more questions than they raise. PMID- 2900137 TI - Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease. AB - The precursor of the Alzheimer's disease-specific amyloid A4 protein is an integral, glycosylated membrane protein which spans the bilayer once. The carboxy terminal domain of 47 residues was located at the cytoplasmic site of the membrane. The three domains following the transient signal sequence of 17 residues face the opposite side of the membrane. The C-terminal 100 residues of the precursor comprising the amyloid A4 part and the cytoplasmic domain have a high tendency to aggregate, and proteinase K treatment results in peptides of the size of amyloid A4. This finding suggests that there is a precursor-product relationship between precursor and amyloid A4 and we conclude that besides proteolytic cleavage other events such as post-translational modification and membrane injury are primary events that precede the release of the small aggregating amyloid A4 subunit. PMID- 2900139 TI - Insulin and phorbol ester stimulate phosphorylation of acetyl-CoA carboxylase at similar sites in isolated adipocytes. Lack of correspondence with sites phosphorylated on the purified enzyme by protein kinase C. AB - 1. The phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) stimulates fatty acid synthesis from glucose in isolated adipocytes with a half-maximal effect at 0.72 microM. In seven batches of cells, the maximal effects of TPA and insulin were 8.5 +/- 1.1-fold and 27.1 +/- 2.1-fold respectively. Insulin also stimulated fatty acid synthesis from acetate 8.9 +/- 0.5-fold (three experiments), but TPA did not significantly increase fatty acid synthesis from this precursor. 2. In contrast to insulin, TPA treatment of isolated adipocytes did not produce an activation of acetyl-CoA carboxylase which was detectable in crude cell extracts. 3. The total phosphate content of acetyl-CoA carboxylase, isolated from adipocytes in the presence of protein phosphatase inhibitors, was estimated by 32P-labelling experiments to be 2.6 +/- 0.1 (5), 3.4 +/- 0.2 (5), and 3.8 +/- 0.2 (3) mol/mol subunit for enzyme from control, insulin- and TPA-treated cells respectively. Insulin and TPA stimulated phosphorylation within the same two tryptic peptides. 4. Purified acetyl-CoA carboxylase is phosphorylated in vitro by protein kinase C at serine residues which are recovered in three tryptic peptides, i.e. peptide T1, which appears to be identical with the peptide Ser Ser(P)-Met-Ser-Gly-Leu-His-Leu-Val-Lys phosphorylated by cyclic-AMP-dependent protein kinase, and peptides Ta and Tb, which have the sequences Ile-Asp-Ser(P) Gln-Arg and Lys-Ile-Asp-Ser(P)-Gln-Arg respectively, and which appear to be derived from a single site by alternative cleavages. None of these correspond to the peptides whose 32P-labelling increase in response to insulin or TPA. Peptides Ta/Tb are not significantly phosphorylated in isolated adipocytes, even after insulin or TPA treatment. Peptide T1 is phosphorylated in isolated adipocytes, but this phosphorylation is not altered by insulin or TPA. 5. These results show that TPA mimics the effect of insulin on phosphorylation, but not activation, of acetyl-CoA carboxylase, i.e. that these two events can be dissociated. In addition, phorbol ester stimulates phosphorylation of acetyl-CoA carboxylase in isolated adipocytes, but this is not catalyzed directly by protein kinase C, and acetyl-CoA carboxylase does not appear to be a physiological substrate for this kinase. PMID- 2900138 TI - Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase. AB - We have examined the sites phosphorylated on acetyl-CoA carboxylase by three protein kinases which have been shown to inactivate the enzyme, i.e. cyclic-AMP dependent protein kinase, acetyl-CoA carboxylase kinase-2 (ACK2, purified from rat mammary gland) and the AMP-activated protein kinase (formerly called acetyl CoA carboxylase kinase-3, purified from rat liver). Each protein kinase phosphorylates two out of three sites (termed 1-3) which have been established by amino acid sequencing. The two sites phosphorylated by each kinase can be recovered on separate peptides, TC1 and TC2, derived by combined digestion of the native enzyme by trypsin and chymotrypsin: TC1 = Ser-2Ser(P)-Met-3Ser(P)-Gly-Leu; TC2 = Arg-Met-1Ser(P)-Phe- Cyclic-AMP-dependent protein kinase phosphorylates sites 1 and 2 exclusively, whereas the AMP-activated protein kinase phosphorylates sites 1 and 3, plus at least one other minor site. ACK2 phosphorylates site 1 and, more slowly, an unidentified site(s) within TC1. We have also established the structures of the single major phosphopeptides (T1 and C1 respectively) which are recovered by HPLC after acetyl-CoA carboxylase phosphorylated by cyclic-AMP-dependent protein kinase is digested with trypsin or chymotrypsin alone. T1 is related to TC1, and has the structure: Ser-Ser(P)-Met Ser-Gly-Leu-His-Leu-Val-Lys. C1 is identical with TC2. We have carried out studies on the correlation of the activity of acetyl-CoA carboxylase with the occupancy of sites 1, 2 and 3 during phosphorylation by each of the three protein kinases. The results suggest that phosphorylation of site 3 is primarily responsible for the large decrease in Vmax produced by the AMP-activated protein kinase, while phosphorylation of site 1 may be primarily responsible for the increase in A0.5 for citrate and more modest depression of Vmax produced by cyclic-AMP-dependent protein kinase and ACK2. Our results emphasize that amino acid sequence information is essential in the unequivocal interpretation of data from phosphopeptide mapping experiments and allow a more complete interpretation of previous data on phosphorylation of acetyl-CoA carboxylase in intact cells. They also open the way to experiments which could establish the physiological roles of these protein kinases in the control of fatty acid synthesis. PMID- 2900140 TI - Analysis of sites phosphorylated on acetyl-CoA carboxylase in response to insulin in isolated adipocytes. Comparison with sites phosphorylated by casein kinase-2 and the calmodulin-dependent multiprotein kinase. AB - We have examined the sites phosphorylated on acetyl-CoA carboxylase in response to insulin in isolated adipocytes. Two tryptic peptides derived from the enzyme become more radioactive after treatment of 32P-labelled cells with insulin. One of these (T4a) accounts for a large part of the total increase in phosphate observed after insulin treatment, and comigrates with the peptide containing the sites phosphorylated in vitro by casein kinase-2. The other may correspond to the 'I' site peptide originally described by Brownsey and Denton in 1982: labelling of this peptide is stimulated at least threefold by insulin treatment, but it is a minor phosphopeptide and, even after insulin treatment, accounts for only about 2.5% of the enzyme-bound phosphate (equivalent to less than 0.1 mol phosphate/mol 240-kDa subunit). Two other major tryptic phosphopeptides (T1 and T4b) labelled in adipocytes do not change significantly in response to insulin, and comigrate with peptides containing sites phosphorylated in vitro by cyclic-AMP-dependent protein kinase and calmodulin-dependent multiprotein kinase respectively. We have sequenced peptides T4a and T4b from acetyl-CoA carboxylase derived from control and insulin-treated adipocytes, and also after phosphorylation in vitro with casein kinase-2 and the calmodulin-dependent multiprotein kinase. The results show that T4a and T4b are forms of the same peptide containing phosphate groups on different serine residues: Phe-Ile-Ile-Gly-Ser4-Val-Ser5-Gln-Asp-Asn-Ser6-Glu Asp -Glu-Ile-Ser-Asn-Leu-. Site 5 was phosphorylated by the calmodulin-dependent protein kinase and site 6 by casein kinase-2. Migration in the T4a position was exclusively associated with phosphorylation in site 6, irrespective of the presence of phosphate in sites 4 and 5. Sites 5 and 6 were partially phosphorylated in control adipocytes, and there were also small amounts of phosphate in site 4. On stimulation with insulin, phosphorylation appeared to occur primarily at site 6, thus accounting for the increase in 32P-labelling of T4a. We were unable to isolate sufficient quantities of the other insulin sensitive peptide to determine its sequence. Our results are consistent with the idea that insulin activates either casein kinase-2, or a protein kinase which has the same specificity as casein kinase-2. The function of this modification is not clear, since phosphorylation by casein kinase-2 has no direct effect on acetyl CoA carboxylase activity. PMID- 2900141 TI - The enantiomeric error frequency of aspartate aminotransferase. AB - The enantiomeric error frequency of aspartate aminotransferase (mitochondrial isoenzyme from chicken) was assessed by adding the enzyme in high concentration (0.89 mM) to a mixture of L-glutamate and 2-oxoglutarate (12 and 1.2 mM, respectively, at pH 7.5 and 25 degrees C). The substrates continuously undergo the transamination cycle under these conditions. Thereby, L-glutamate is progressively racemized, a 1:1 ratio of two enantiomers being reached within 240 h. The enantiomeric error frequency, i.e. the ratio of the rate of D-glutamate production and the rate of the transamination reaction with glutamate and 2 oxoglutarate as substrates, is 1.5 x 10(-7). D-Glutamate is also converted to a 1:1 racemic mixture. The racemizing activity of a mixture of free pyridoxal 5' phosphate and pyridoxamine 5'-phosphate is about two orders of magnitude lower than that of aspartate aminotransferase. The error frequency of the enzyme in the case of the C4 substrate pair aspartate and oxalacetate is 3.4 x 10(-8), i.e. 4 times lower than that with the C5 substrate pair. PMID- 2900142 TI - Microcirculatory effects of somatostatin in acute pancreatitis. AB - Somatostatin, a 28-amino-acid inhibitory polypeptide has been advocated for the treatment of upper gastrointestinal bleeding and acute pancreatitis. This study examines the effect of somatostatin in acute hemorrhagic pancreatitis in piglets (n = 12), weighing 8-12 kg. Six animals served as controls, and received only fluid resuscitation (0.9%, NaCl, 20 ml/kg/h). Six animals received somatostatin treatment consisting of a 15 micrograms/kg bolus i.v. given simultaneously with the induction of pancreatitis, and treatment continued with an intravenous infusion (15 micrograms/kg/h) for 5 h. Cardiac output, heart rate, blood pressure, arterial pO2, hematocrit and serum amylase were recorded before and each hour during the experiment. Regional blood flow in the gastrointestinal area was measured using the microsphere method. The microspheres labelled with three different isotopes were administered before the experiment and at 2 and 5 h, respectively. There was a significant decrease in the cardiac output (p less than 0.05) and an increase in systemic blood pressure in the somatostatin-treated group (p less than 0.025). Pancreatic blood flow decreased by 43% following somatostatin infusion. The decreases at 2 and 5 h were highly significant (p less than 0.005). Blood flow to the mucosal but not muscular region of the stomach was decreased by somatostatin. This study suggests that somatostatin might be harmful in acute pancreatitis due to its adverse effects on pancreatic blood flow and cardiac output. However, somatostatin may be effective in reducing gastrointestinal bleeding. If the drug is used clinically, careful monitoring of the cardiac output is necessary. PMID- 2900143 TI - Comparison of the acute haemodynamic effects of bopindolol and propranolol at rest and during supine exercise. AB - The acute cardiovascular effects of two beta-adrenoceptor blocking agents, bopindolol and propranolol, were compared in a randomized study in 16 male patients with coronary heart disease. All patients had had an uncomplicated acute myocardial infarction at least 8 weeks earlier. The two drugs reduced the arterial blood pressure to the same extent, both at rest and during exercise. As heart rate and stroke volume were also decreased, cardiac output was reduced, whereas systemic vascular resistance was increased at rest and during exercise. Left ventricular filling pressure was increased. No statistically significant differences in these variables were seen between the two groups. PMID- 2900144 TI - Ethnic differences in response to beta-blockade: fact or artefact? A study with bisoprolol and propranolol. AB - A randomized, double-blind, placebo-controlled study was performed in 8 white and 8 black volunteers matched for sex, age and mass. The effect of 3 intravenous doses of a new, cardioselective beta-adrenergic blocker, bisoprolol, on the heart rate increase after standardized exercise was compared to that of 3 doses of propranolol. As described previously for propranolol, black volunteers showed less response than whites to beta-blockade assessed in terms of the reduction in exercise-induced tachycardia. The effects of the two beta-blockers were similar and the apparent ethnic difference was seen with both drugs. It has previously been shown that black volunteers have a higher intrinsic heart rate (i.e. heart rate after parasympathetic and beta-adrenergic blockade of the heart) than whites, but their resting heart rates are similar because of greater parasympathetic tone in blacks. When exercise-load was calculated as increase in heart rate above that after atropinization, no ethnic differences were seen. It is suggested that in populations that are heterogenous in terms of the heart rate increase after atropine, work load should be standardized in terms of the increase in heart rate over the atropine heart rate rather than on absolute heart rate. The apparent ethnic difference represents a flaw in methodology as applied to a heterogenous volunteer population. PMID- 2900145 TI - Variation in serum binding of tertatolol mediated by disease-induced modification of alpha-acid glycoprotein concentration. AB - The serum concentrations of alpha 1-acid glycoprotein (AAG), albumin (HSA) and non-esterified fatty acids, and the serum binding of tertatolol were measured in four groups of individuals: healthy control subjects (n = 24), and patients with inflammation (n = 28), and hepatic (n = 20) and renal (n = 27) insufficiency. Serum binding of tertatolol was increased in patients with inflammation (94.6%), decreased in patients with hepatic insufficiency (88.8%) and it was unchanged in patients with renal insufficiency (92.8%) as compared to controls (92.7%). Multivariate analysis indicated that the changes were mainly related to concomitant changes in AAG concentration, which could account for 57% of intersubject variability in the bound/free ratio, and to a lesser extent in HSA, which accounted for only 4% of the variability in the binding. The data show that the free fraction of the basic drug tertatolol in serum is affected by pathological conditions that cause changes in AAG concentration. PMID- 2900147 TI - Definition of the RFLP alleles in the human immunoglobulin IGHG gene locus. AB - In order to define more precisely the polymorphism of the human immunoglobulin IGHG (C gamma) genes and, consequently, to understand the structure and evolution of this multigene family, we have investigated the Restriction Fragment Length Polymorphisms (RFLP) of the IGHG genes in 113 unrelated individuals and 18 families. Using the restriction enzymes Bam HI, Sac I and Eco RI, and hybridization to a IGHG probe and to a specific IGHG3 (C gamma 3) probe, we describe 47 different restriction fragments (RF) in the IGHG locus, allowing us to define at least 15 RFLP alleles for the different IGHG genes. Our data demonstrate that the restriction fragment length polymorphism is occasionally due to the presence or absence of a given restriction site as a consequence of a point mutation, such as the creation of an Eco RI site, at the codon 3 of exon 2 in one IGHG4 allele (IGHG4*D2). However, most of the RFLP we observed seem to result from the insertion or deletion of a few hundred base pairs as illustrated by the IGHG3 polymorphism. PMID- 2900146 TI - Haemodynamic effects of short-term treatment with bopindolol in essential hypertension. AB - Ten patients (mean age 53 years) with essential hypertension have been studied at rest and during exercise following oral treatment for 6 weeks with a new beta adrenoceptor blocking agent, bopindolol. The treatment caused a significant decrease in systolic and diastolic arterial blood pressure and heart rate, both at rest and during exercise. Stroke volume fell, too, and therefore so did cardiac output, whereas the systemic vascular resistance was increased. Left ventricular filling pressure was elevated both at rest and during exercise following bopindolol therapy. However, a different haemodynamic pattern was noted in patients with elevated total peripheral resistance prior to therapy (Group 1) compared to patients with normal or subnormal peripheral resistance (Group 2). A decrease in systemic vascular resistance seemed to be the cause of the fall in blood pressure in Group 1, as the expected increase in vascular resistance did not occur, whereas a reduction in cardiac output was of greater importance in Group 2. During exercise the lowering of arterial blood pressure in both groups was mediated by a reduction in cardiac output. PMID- 2900148 TI - Restriction fragment haplotypes in the human immunoglobulin IGHG locus and their correlation with the Gm polymorphism. AB - Of the four human IgG subclass heavy chain (IGHG) genes, three--IGHG1, IGHG2 and IGHG3--have allelic forms which encode antigenic determinants called G1m, G2m and G3m allotypes for markers of the IgG1, IgG2 and IgG3 molecules. The alleles at these three closely linked loci are transmitted as Gm haplotypes, together with the IGHG4 and the IGHGP (or pseudo gamma) genes. Restriction Fragment Length Polymorphisms (RFLPs) have been described for all these IGHG genes, allowing us to define at least 15 RFLP alleles (N. Ghanem et al., Eur. J. Immunol. 1988. 18:1059). In this article, we determine unambiguously the Gm alleles and haplotypes and the associated RFLPs in French, Lebanese and Tunisian families, chosen for the various Gm phenotypes of their members, in order to correlate both these polymorphisms and to know the evolution of the IGHG multigene family. We were able to assign all the IGHG alleles to the Gm alleles and to their linked IGHG4 and IGHGP genes allowing us to define restriction fragment haplotypes of the IGHG gene family. PMID- 2900149 TI - Activation signals via CD2 molecule and interleukin 2 receptor act in synergy for helper function induction. AB - The membrane CD2 molecule appears to play an important role in T cell activation. Indeed, T cell stimulation by some combinations of anti-CD2 monoclonal antibodies (mAb) can result in antigen-independent expression of helper function as assessed by proliferation and lymphokine secretion. We report here that T cell stimulation by a combination of two anti-CD2 mAb recognizing GT2 and T11(1) epitopes, respectively, cannot alone induce T helper clones to proliferate when preincubated in culture medium devoid of exogenous interleukin 2 (IL2). The concerted action of both anti-GT2 + T11(1) mAb and exogenous recombinant IL2 is required to induce cloned helper T cells to produce IL 2 and interferon-gamma to significantly increase IL2 receptors (IL2R) and finally to divide by an autocrine mechanism, whereas each signal alone has no effect. This therefore suggests that, under some conditions of CD2 stimulation, two minimal signals may be delivered through CD2 and IL2R and act synergistically to achieve a complete expression of T helper cell functions. Moreover, analysis of phosphatidylinositol and phosphatidic acid metabolic changes mediated by each signal separately or together suggests that, in this model, IL2 increases the phosphoinositide turnover induced by anti-CD2 antibodies up to a level required for helper function acquisition. PMID- 2900150 TI - T cell activation: distinct pathways involve phosphorylation of different cellular proteins. AB - The murine T cell clone D10.G4.1 can be induced to proliferate by monoclonal antibodies (mAb) to the T cell receptor (TcR) or to Thy-1 molecules. When cells were stimulated by anti-TcR mAb, a group of 4 proteins (19-25 kDa) was specifically phosphorylated. This effect was completely mimicked by the Ca2+ ionophore A23187, whereas only two of these proteins (19 kDa and 25 kDa) were phosphorylated after cell exposure to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate. By contrast, anti-Thy-1 mAb had no effect on the phosphorylation of these proteins, but induced specifically the phosphorylation of a protein of 32 kDa. These results therefore demonstrate that distinct activating pathways in T cells involve the phosphorylation of different proteins, suggesting that the stimulation of protein kinases in T lymphocytes is an early event in cell activation. PMID- 2900152 TI - Vascular postsynaptic effects of some 5-HT1-like receptor agonists in the pithed rat. AB - 5-HT induced an increase in blood pressure in the pithed rat which was antagonized by LY 53857 a selective 5-HT2 receptor antagonist. It was not antagonized by spiroxatrine, MDL 72222, idazoxan or AR-C 239, respectively 5-HT1 like and 5-HT3 receptor antagonists, alpha 2- and alpha 1-adrenoceptor antagonists. 5-MeODMT also induced an increase in blood pressure which was antagonized by LY 53857 but not by the other 5-HT receptor antagonists and alpha adrenoceptor antagonists used, suggesting a 5-HT2 component in the pressor effect of 5-MeODMT. The maximal effect of 5-MeODMT was less marked than that of 5-HT. 8 OH-DPAT, RU 24969 and TFMPP were far less effective than 5-HT and 5-MeODMT to increase blood pressure. In contrast, 5-CT induced a vasodepressor effect. It is therefore suggested that the vasoconstriction induced by 5-HT and by 5-MeODMT in pithed rats could be due mainly to the selective stimulation of postjunctional 5 HT2 receptors because selective alpha 1- and alpha 2-adrenoceptor antagonists were ineffective against the vasoconstrictor effects of 5-HT and 5-MeODMT. The relative lack of effect of 8-OH-DPAT, RU 24969 and TFMPP to increase blood pressure suggested that postjunctional 5-HT1-like receptors play only a minor role - if any - in 5-HT induced vasoconstriction in the pithed rat. PMID- 2900151 TI - Development of autoreactive L3T4+ T cells from double-negative (L3T4-/Ly-2-) Thy 1+ spleen cells of normal mice. AB - Thy-1+/L3T4-/Ly-2- spleen cells were purified from normal C57BL/6 (B6) and C,B-17 mice. Cells within this subset expressed the T cell receptor (TcR) for antigen: the majority of cells in this subset were CD3+; a fraction of the cells was stained with the monoclonal antibody (mAb) F23.1; and the TcR molecule was immunoprecipitable with mAb F23.1 from cells within this subset. In limiting dilution analyses, about 1/30 cells within this subset were growth inducible in vitro by stimulation with phorbol myristate acetate (PMA) plus ionomycin; conditioned media containing interleukin (IL) 1, IL2, IL3 or IL4 activity neither triggered nor promoted in vitro growth of these cells. The in vitro generated T cells displayed the Thy-1+/L3T4+/Ly-2- surface phenotype and were self-reactive, i.e., proliferated preferentially in response to syngeneic stimulator cells, and secreted IL2 and IL3 only in response to syngeneic but not allogeneic stimulator cells. The proliferative response of these cells to syngeneic stimulator cells was blocked by anti-self Ia mAb. This autoreactive helper T cell subset was not inducible in purified Thy-1+ spleen cell subsets from athymic nude mice or scid mice. Autoreactive helper T cells did not express detectable levels of the IL2 receptor (IL2R), and their proliferative response was not blocked by anti-IL2R mAb. From PMA plus ionomycin-stimulated double-negative Thy-1+ spleen cells, 14 T cell clones were established in long-term culture which displayed the CD3+CD4+CD8 surface phenotype and were self-reactive. PMID- 2900153 TI - Continuous slow release of low levels of diazepam produces tolerance to its depressant and anxiolytic effects on the startle reflex. AB - Development of tolerance to the depressant effects of diazepam on the acoustic startle reflex and to the blockade of fear-potentiated startle, a measure of fear or anxiety in rodents, was evaluated after chronic administration via continuous release from implanted diazepam-filled silastic capsules or daily intraperitoneal (i.p.) injections. After continuous exposure to diazepam via capsule implants, complete tolerance occurred to the depressant effects of diazepam on startle and partial tolerance occurred to the antifear effects. In contrast, no tolerance was observed after daily i.p. injection with comparable amounts of diazepam (5 mg/kg) although tolerance could be produced by daily i.p. injections of a much higher dose of diazepam (20 mg/kg). These data suggest that tolerance to at least some behavioral effects may be much easier to produce with continuous rather than intermittent occupation of benzodiazepine receptors. PMID- 2900154 TI - Characterization of the selectivity, specificity and potency of medetomidine as an alpha 2-adrenoceptor agonist. AB - Medetomidine (4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole) was tested for alpha 2-adrenoceptor agonist activity and compared to several reference agents. In binding studies carried out with rat brain membrane preparations, medetomidine showed high affinity for alpha 2-adrenoceptors, as measured by the displacement of [3H]clonidine (Ki 1.08 nM compared to 1.62, 3.20, 6.22 and 194 nM for detomidine, clonidine, UK 14,304 and xylazine, respectively). The affinity of medetomidine for alpha 1-adrenoceptors, as measured by [3H]prazosin displacement, was much weaker, yielding a relative alpha 2/alpha 1 selectivity ratio of 1620 which is 5-10 times higher than that of the reference compounds. Medetomidine caused a concentration-dependent inhibition of the twitch response in electrically stimulated mouse vas deferens with a pD2 value of 9.0 compared to that of 8.6, 8.5, 8.2 and 7.1 for detomidine, clonidine, UK 14,304 and xylazine, respectively. The effect of medetomidine was antagonized by idazoxan. In anaesthetized rats, medetomidine caused a dose-dependent mydriasis which could be reversed by alpha 2-adrenoceptor blockade. In receptor binding experiments and isolated organs medetomidine had no affinity or effects on beta 1-, beta 2-, H1, H2, 5-HT1, 5-HT2, muscarine, dopamine, tryptamine, GABA, opiate and benzodiazepine receptors. Based on these results, medetomidine can be classified as a potent, selective and specific alpha 2-adrenoceptor agonist. PMID- 2900155 TI - Evaluation of stem cell reserve using serial bone marrow transplantation and competitive repopulation in a murine model of chronic hemolytic anemia. AB - Serial transplantation and competitive repopulation were used to evaluate any loss of self-replicative capacity of bone marrow stem cells in a mouse model with increased and persistent hemopoietic demands. Congenic marrows from old control and from young and old mice with hereditary spherocytic anemia (sphha/sphha) were serially transplanted at 35-day intervals into normal irradiated recipients. Old anemic marrow failed or reverted to recipient karyotype at a mean of 3.5 transplants, and young anemic marrow reverted at a mean of 4.0 transplants, whereas controls did so at a mean of 5.0 transplants. In a competitive assay in which a mixture of anemic and control marrow was transplanted, the anemic marrow persisted to 10 months following transplantation; anemic marrow repopulation was greater if anemic marrow sex matched with the host. It is possible that lifelong stress of severe anemia decreases stem cell reserve in the anemic sphha/sphha mouse marrow. However, marginal differences in serial transplantation number and the maintenance of anemic marrow in a competition assay would suggest that marrow stem cells, under prolonged stress, are capable of exhibiting good repopulating and self-replicating abilities. PMID- 2900156 TI - High-affinity uptake of L-[3H]glutamate and D-[3H]aspartate during postnatal development of the hippocampal formation: a quantitative autoradiographic study. AB - Quantitative autoradiography was used to determine the topographical and time patterns of L-[3H]glutamate and D-[3H]aspartate high-affinity uptake system in the hippocampal formation of the rat during postnatal development. Extended control experiments were performed to verify the specificity of labelling. For short incubation periods of 3-10 min, the data demonstrated a conspicuously low rate of glutamate accumulation in the hippocampal formation of newborn animals and a marked increase in labelling of hippocampal neuropil areas during the first weeks of postnatal life. Our autoradiographic data on developmental increase in glutamate high-affinity uptake levels are consistent, in terms of time and topography, in many ways with other parameters of maturation of glutamatergic and/or aspartatergic structures in the hippocampal formation. PMID- 2900157 TI - Bradykinin activates tyrosine hydroxylase in rat pheochromocytoma PC-12 cells. AB - Tyrosine hydroxylase is activated in PC-12 cells by bradykinin in a concentration dependent manner with maximal stimulation occurring at 1 microM. This stimulatory effect occurs within 15 s and is maximal at 5 min. This stimulation is due to an increase in the affinity of tyrosine hydroxylase for its pterin cofactor, and can be blocked by a specific bradykinin receptor antagonist. These data indicate that bradykinin can regulate the activity of tyrosine hydroxylase in PC-12 cells. PMID- 2900158 TI - Negative interactions between phosphorylation of acetyl-CoA carboxylase by the cyclic AMP-dependent and AMP-activated protein kinases. AB - We have reported previously that cyclic AMP-dependent protein kinase phosphorylates two sites on acetyl-CoA carboxylase (site 1: Arg-Met-Ser(P)-Phe, and site 2: Ser-Ser(P)-Met-Ser-Gly-Leu), while the AMP-activated protein kinase also phosphorylates site 1, plus site 3 (Ser-Ser-Met-Ser(P)-Gly-Leu), the latter being two residues C-terminal to site 2. We now report that prior phosphorylation of site 2 by cyclic AMP-dependent protein kinase prevents the subsequent phosphorylation of site 3 and the consequent large decrease in Vmax produced by the AMP-activated protein kinase. Similarly, prior phosphorylation of site 3 by the AMP-activated protein kinase prevents subsequent phosphorylation of site 2 by cyclic AMP-dependent protein kinase. PMID- 2900159 TI - Neurotransmitters, cytokines, and the control of alveolar bone remodeling in orthodontics. AB - This article described research aimed at testing the hypothesis that tissue remodeling during orthodontic tooth movement is modulated, at least in part, by factors derived from the nervous and vascular (immune) systems. Specifically, the neurotransmitters SP and VIP and the cytokines IL-1 alpha and IL-1 beta were localized immunohistochemically in paradental tissues of cat canines that had been treated by the application of an 80 g tipping force for 1 hour to 14 days. Increased staining (concentrations) of these agents were found in areas of PDL tension and compression at different time periods. Moreover, administration of SP and IL-1 beta to human PDL fibroblasts in vitro for 1 to 60 minutes resulted in significant increases in the levels of the intracellular "second messenger" cAMP, as well as of PGE2, a plasma membrane-associated fatty acid believed to serve as a local regulator of bone cell activity. Taken together, these results tend to support the hypothesis that neurotransmitters and cytokines play a regulatory role in orthodontic force-induced alveolar bone remodeling. Consequently, determination of the cytokine synthetic activity by leukocytes of orthodontic patients may inform about their alveolar bone remodeling potential. PMID- 2900160 TI - Safe motherhood. PMID- 2900161 TI - Maternity care in developing countries: relevance of new technological advances. AB - It is suggested that improved maternity care in the developing world depends primarily on the increased provision of cost-effective, basic, easily accessible maternity care services. Expensive new technologies should be judged by their effectiveness, safety, technical feasibility, cost (including operating and maintenance expenses) and local need. After identifying the major causes of morbidity and mortality, priority should be given to interventions applicable at the local level and which do not require highly or specially trained educated personnel. PMID- 2900162 TI - The problem of grandmultiparity in current obstetric practice. AB - A retrospective analysis of 646 Arab grandmultiparas who booked for hospital confinement between 1983 and 1985 was carried out. The results were compared with that of non-grandmultiparas during the same period. In the grandmultiparas, the incidences of gestational diabetes, hypertension rheumatic heart disease, antepartum, postpartum hemorrhage and macrosomic infants were increased. However, contrary to some previous reports the incidences of anemia, cesarean sections, induced labor, dysmaturity and perinatal deaths were decreased. This is thought to be due to the provision of modern specialist perinatal care and improved socioeconomic standards. PMID- 2900163 TI - How does pre-eclampsia influence thermal conductivity of the skin? AB - To evaluate the thermal conductivity characteristics in relation to pre eclampsia, deep body temperature (DBT) was measured using the zero-heat flow method in non-pregnant healthy subjects, normal pregnant subjects, pregnant subjects with essential hypertension and in pre-eclamptics. The duration of the initial rise in peripheral DBT was significantly prolonged in the pre-eclamptics, as compared with findings in the other three groups. The results indicate that pre-eclamptics have a decrease of thermal conductivity of the skin. PMID- 2900165 TI - The impact of diagnostic ultrasound on the prediction of intrauterine growth retardation in developing countries. AB - The purpose of this report is to throw light on the problem of intrauterine growth retardation in our society, and to show how this situation could be affected by the introduction of diagnostic ultrasound in our antenatal service. A series of 828 pregnant women were serially examined by ultrasound during the course of pregnancy. Among the whole series (no. 828) there were 98 growth retarded neonates (11.8%). Antenatal ultrasonic evaluation could predict 89.7% of these cases, while only 34.7% of cases could have been predicted by fundal palpation. Among the different etiological factors, maternal anemia was the most common (25%). PMID- 2900164 TI - Maternity care monitoring: a contrast at two levels of health care delivery in Ibadan, Nigeria. AB - The obstetric performance of women delivering at two hospitals in Ibadan is compared in this study. The prevalence of high-risk pregnancies at the tertiary level hospital (University College Hospital) was higher than that of the secondary level hospital (Oluyoro Catholic Hospital). Consequently, the cesarean section rate of the UCH (21.8%) was higher than that at the OCH (2.3%). Similarly, the maternal mortality (3.5 per 1000) and perinatal mortality (60.2 per 1000) at the UCH were significantly higher than at the OCH, 2.0 per 1000 and 9.8 per 1000, respectively. The need for a national birth survey based on a representative sample of all the different types of health establishments in Nigeria was stressed. PMID- 2900166 TI - Risk factors for low birthweight in Singapore: strategies for prevention. AB - An analysis of 9399 consecutive singleton births delivered at this unit is presented. The incidence of low birthweight (less than 2500 g) was 7.4%. Further analysis of the 698 low birth weight babies indicated that a variety of socio demographic risk factors are operational in the etiology of low birthweight. Many of these are preventable before pregnancy so that the implementation of preventive Public Health measures utilising appropriate technology at least in developing countries may be socially and economically preferable to continued financial investment in intensive perinatal services. PMID- 2900167 TI - Serum complement levels in normal pregnancy and pregnancy-induced hypertension. AB - Serum complement assay (CH50) was carried out in urban low-income women belonging to the following groups: (i) non-pregnant and non-lactating women; (ii) pregnant women in different periods of gestation; (iii) women suffering from pregnancy induced hypertension. Serum CH50 titers showed significant increase in the second and third trimester pregnancies as compared to non-pregnant, non-lactating women. There were no differences in CH50 levels between women suffering from pregnancy induced hypertension and those with normal pregnancy of comparable period of gestation. Nutritional status did not seem to have any influence on complement titers. PMID- 2900168 TI - Outcome of cesarean section in twin pregnancy. AB - In an 8-year period (January 1978 to December, 1985), the 17,379 deliveries at the University of Benin Teaching Hospital (UBTH) consisted of 2089 cesarean sections (12.0%), 56 of which were associated with twin pregnancy. The main indications for cesarean section on the twin pregnancies were antepartum hemorrhage (placenta previa), malpresentation, cervical dystocia and previous cesarean section. The maternal mortality rate was 2% for all twin mothers delivered by cesarean section. There was no statistical difference in perinatal mortality rates (PMR) for all twin deliveries, vaginal twin deliveries and deliveries by cesareans section which were 111,113 and 100 per 1000 births, respectively. In the case of a retained second twin, however, recorded PMR was significantly higher (133 per 1000 births). Consideration of more liberal recourse to cesarean section in all cases of twins may reduce these unacceptably high perinatal death rates in twin pregnancy. PMID- 2900169 TI - Perinatal mortality at King Fahd Hospital of the University Al-Khobar, Saudi Arabia. AB - The perinatal deaths of all singleton births that occurred at King Fahd Hospital of the University, Al-Khobar, Saudi Arabia during a 4-year period are analysed. The causes of death are classified into 12 groups using an extended modification of the Aberdeen classification. There were 165 perinatal deaths in 8057 singleton births, giving a perinatal mortality rate of 20.47 per 1000 total births. Fetal malformations occurred in 29 (17.57%) cases. Of the remaining 136 normal infants, 77 (56.6%) were stillbirths and 59 (43.4%) died within 1 week of delivery. Spontaneous premature labor was the commonest cause of death (23.52%) followed by birth trauma (11%) and maternal diseases (9.55%). The cause of death was not known in 22 (16.17%) cases. In conclusion, prevention of premature labor, better intrapartum fetal monitoring, early recognition of fetal distress and improvement of neonatal care should reduce the perinatal mortality rate. PMID- 2900170 TI - Four-year follow-up of electrocoagulation and tubal ring sterilizations in Costa Rica. AB - An earlier analysis of 299 laparoscopic sterilizations comparing electrocoagulation and tubal ring occlusion techniques found no significant differences in rates of surgical complications. The risk of potentially serious complications, such as bowel/bladder burns, was considered higher with electrocoagulation be the preferred technique. Examination of the same women through 48 months poststerilization between the two techniques with respect to the incidence of gynecologic surgery performed subsequent to sterilization. Gynecologic abnormalities were similar for women in both groups. The rate of pregnancy was higher for tubal rings than for electrocoagulation (2.1 compared to 0.7 at 48 months) but this difference was not statistically significant. PMID- 2900171 TI - A clinico-pathologic study of ovarian neoplasm. AB - A series of 96 patients who were diagnosed with 120 ovarian neoplasms at surgery have been reviewed. Nine types of benign ovarian cysts were encountered. Benign cystic teratoma with an incidence of 30% was the commonest tumor. The majority of these were in the 20-30 year age range. The mean age of the patients with mucinous cyst adenoma and benign cystic teratoma was significantly less (P less than 0.05) than those with serous cyst adenoma. The incidence of ovarian malignancies of 8.3% was low, and none of the malignancies was bilateral. There was a high incidence of 8.3% of malignant change in benign cystic teratomas. Abdominal pain and swelling were the symptoms most frequently experienced in patients with benign ovarian neoplasms. PMID- 2900172 TI - Effect of human menopausal gonadotrophin on the non-pregnant uterine response to intrauterine administration of prostaglandin E2. AB - The effect of intrauterine instillation of 50 micrograms of prostaglandin E2 (PGE2) on the non-pregnant human uterus was evaluated in 10 volunteers, before and after systemic administration of human menopausal gonadotrophin (HMG). The cases were either in the early proliferative (n = 5) or late secretory (n = 5) phases of the cycle. Before HMG administration, the uterus responded to local PGE2 by stimulation in all the cases. After HMG treatment, no response to PGE2 was detected in eight cases and a decrease in uterine tonus was observed in two cases. The implications of these findings in certain physiological and pathological conditions relating to reproduction are discussed. PMID- 2900173 TI - Infertility in Central Africa: infection is the cause. AB - Determinants of infertility were studied in 340 women in Eastern Gabon, an area situated in the "infertility belt" of Central Africa. Fallopian tube occlusion was diagnosed in 82.8% of cases, showing the importance of infection-related causes. Women with tubal occlusion did not differ significantly from women with normal tubes in obstetrical history or prevalence of Neisseria gonorrhoeae or Chlamydia trachomatis on endocervical culture. Antecedents of pelvic inflammatory disease or a pelvic mass were significantly more common in the group with tubal occlusion. This group also had a significantly higher prevalence of serum chlamydial antibodies at a titer of 1/64 or higher. Hormonal factors were found in 31.7% of women, a cervical factor in 29.0% and mechanical factors in 5.6%. No diagnosis could be made in 12.2% of cases. During the investigation, 4.4% of women became pregnant. The predominance of infectious related causes of infertility makes it imperative to focus resources on prevention programs of upper genital tract infections in women. PMID- 2900175 TI - Abortion-related morbidity and mortality in Benin City, Nigeria: 1973-1985. AB - In a 13-year review of maternal deaths at the University of Benin Teaching Hospital, Benin City, abortion was one of the three major causes of death, accounting for 37 (22.4%) out of the 165 deaths. Induced abortion was responsible for 34 (91.9%) of these deaths. The usual victim is the teenage, inexperienced school girl who has no ready access to contraceptive practice. Death was mainly due to sepsis (including tetanus), hemorrhage and trauma to vital organs, complications directly attributable to faulty techniques by unskilled abortion providers, a by-product of the present restrictive abortion laws. Total overhaul of maternal child health services and the family health education system, as well as integration of planned parenthood at primary health care level into the health care delivery system, are suggested. Contraceptive practice should be made available to all categories of women at risk, and the cost subsidised by governmental and institutional bodies. Where unwanted pregnancies occur, the authors advocate termination in appropriate health institutions where lethal and sometimes fatal complications are unlikely to occur. In effect, from the results of this study and a review of studies on abortion deaths in Nigeria and other developing countries, it is obvious that a revision of abortion laws as they operate, notably in the African continent, is overdue. PMID- 2900174 TI - The role of the levonorgestrel intrauterine device in the prevention and treatment of iron deficiency anemia during fertility regulation. AB - Hematocrit and blood ferritin were assayed in 43 women using a levonorgestrel intrauterine device (LevoNg-IUD), 49 using the Copper T-380 Ag (T-Cu 380 Ag), 27 using the Lippes loop and 30 non-IUD users as controls. The mean duration of use was 41 months for the three IUD groups. Women not using IUDs and with similar age, parity, years of schooling and family income as users had a normal mean hematocrit and ferritin, but 30% had low hematocrit (below 38%) and 43% had low ferritin (below 11 ng/ml). After prolonged use of the IUDs, 26% of users of Lippes loop, 22% of users of T-Cu 380 Ag and only 2% of users of LevoNg-IUD had subnormal hematocrit; 70%, 55% and 14%, respectively, had low ferritin. Thus, in a population with high incidence of anemia, the use of LevoNg-IUD appears to reduce the proportion of women with clinical anemia and with depletion of their iron store. PMID- 2900176 TI - Endocrine and morphological study of a case of ovarian sex-cord tumor with annular tubules in a woman with Peutz-Jeghers syndrome. AB - A bilateral ovarian sex-cord tumor with annular tubules (SCTAT) was incidentally discovered in an amenorrheic patient with Peutz-Jeghers syndrome during conservative surgery in which a small non-capsulated mass was removed from each ovary. Ovulation was then induced over two consecutive cycles with urinary gonadotropins; the couple did not conceive because of a male infertility factor. Hysterectomy and bilateral oophorectomy were performed to prevent recurrence and avoid the possibility of a cervical malignant adenoma. Immunohistochemistry of the SCTAT showed positivity for estradiol and testosterone similar to that of Sertoli and granulosa cell tumors; progesterone was not detected in any cellular component of the neoplasia. Electron microscopy showed that the neoplasm consisted of numerous solid cords of cells surrounded by fibrillary layers of basal lamina, as well as central hyaline bodies. Two types of cells, clear and dark, were noted; clear cells were predominant and intermixed with scattered dark cells. No crystalloids or Charchot-Bottcher filaments were detectable in the tumors. PMID- 2900177 TI - Management of vesico-uterine fistulae: a report of six cases. AB - Six cases of vesico-uterine fistulae caused by cesarean section in four and pelvic trauma in two cases were treated during the past 15 years. Both the cases of vesico-uterine fistulae due to pelvic trauma and one case of vesico-uterine fistula due to cesarean section in whom the fistula was detected in the early post-operative period, could be managed successfully by suprapubic urinary diversion and control of infection. Two patients who were seen more than 1 year after the cesarean section, were cured by trans-abdominal closure of the fistula with omental interposition. One patient who reported 3 months after the cesarean section was managed by estrogen and progesterone-induced amenorrhea. The management protocol for vesico-uterine fistula should thus be individualised taking into consideration the etiology, and time interval between its occurrence and institution of treatment regimen. PMID- 2900178 TI - Pelvic fibromatoses--a rare gynecological entity. AB - A rare case of pelvic fibromatoses is reported. This condition is rarely encountered in gynecological practice but when encountered, creates a diagnostic and therapeutic challenge. The reported patient highlights the difficulties encountered in surgical excision (done twice) and illustrates the local aggressive growth behavior of this entity. PMID- 2900179 TI - WHO issues statement on social aspects of AIDS control. PMID- 2900181 TI - [Oral sedation in dental practice: personal experience]. PMID- 2900180 TI - [Hepatic involvement in HIV 1 virus infection]. AB - One hundred consecutive patients with serum antibodies against HIV 1 were evaluated for the prevalence and the type of liver injury. According to the CDC classification, 16 patients belonged to group II (asymptomatic patients), 47 to group III (persistent generalized lymphadenopathy) and 37 to group IV (11 constitutional disease, 19 secondary infectious diseases, 5 secondary cancers, one chronic lymphoid interstitial pneumonitis and one visceral leishmaniasis). Liver histology was studied in 32 patients. Clinical, biological and histologic abnormalities were assessed according to the clinical group and to the number of T4 lymphocytes. The prevalence of HBV infection was determined by HBV DNA and monoclonal antibodies. Clinical hepatic abnormalities were rare (13 p. 100) and no difference was found between groups. Transaminases or GGT activities were elevated in 60 p. 100 of all cases. Serum GGT activity was higher and serum albumin lower in patients in group IV. HBV infection markers were less frequently found in patients with opportunistic infection (74 p. 100) than in asymptomatic patients (100 p. 100; p less than 0.05). Prevalence of serum HBsAg detected by poly- or monoclonal antibodies was very high (29 p. 100) in all clinical groups. Prevalence of serum HBsAg detected only by monoclonal antibodies (10 p. 100) suggest infection of these patients by an HBV variant. Of the 32 patients undergoing liver histology, only 5 (16 p. 100) had signs of activity. There was no association between clinical or histologic signs and the number of T4 lymphocytes per ml. Alkaline phosphatase, ASAT and GGT activities were higher and serum albumin lower in patients with less than 200 T4 lymphocytes per ml. PMID- 2900183 TI - [Prenatal diagnosis of cystic fibrosis with molecular genetic methods]. PMID- 2900184 TI - [Osteoporosis: an avoidable fate]. PMID- 2900182 TI - Functional hyperthermia due to central dopaminergic impairment. AB - The clinical cases described are characterized by rigidity, mutism and hyperthermia, with cutaneous pallor and diaphoresis. This symptomatology marks the "malignant neuroleptic syndrome" and can be found, at times, in parkinsonians on "drug holiday". The cases described, which comprehend patients with both disorders, lead us to a single pathogenetic hypothesis: a central dopaminergic impairment. Hyperthermia, secondary to functional hypothalamic deficiency, is maintained by defective heat dispersion due to the lack of cutaneous vasodilation. PMID- 2900185 TI - Clinical evaluation of the cardiovascular effects and the pharmacokinetics of benalfocin and its metabolite in healthy subjects during repeated dosing. AB - The cardiovascular effects and the pharmacokinetics of a new selective alpha-2 adrenoceptor antagonist, benalfocin, and its active metabolite, both compounds with a similar receptor affinity profile, were examined in healthy volunteers during repeated dosage. Significant diastolic blood pressure lowering effects were observed on the first and the last day of the treatment persisting throughout the dosage interval. Furthermore, heart rate reductions were found on these days which were significantly correlated with both the parent compound's and the metabolite's plasma concentrations and their sum. Pharmacokinetics remained unchanged after a 1-wk oral dosing as compared to a single oral dose; the plasma half-life of the metabolite was 3-fold longer than that of the parent compound. In normotensive subjects, benalfocin produced blood pressure and heart rate reducing effects, the latter being more correlated with the metabolite's plasma concentrations. Furthermore, results suggest that the compound's known cholinergic effects may be particularly related to the metabolite and that this molecule is an interesting cardiovascular compound. PMID- 2900186 TI - Somatostatin in the management of gastrointestinal hemorrhage: bleeding ulcers. AB - Stress ulcers are characterized by difficult management and poor prognosis. They currently represent a complication in the clinical course of other conditions, mainly shock states. The pathogenesis of stress ulcers is not well understood although the role of hypovolemia leading to energetic deprivation and insaturation of anaerobic cellular metabolism have been carefully studied. Somatostatin has been found to reduce the incidence of experimental stress ulcers. In the clinic, patients with duodenal ulcers were found to exhibit a low number of antral D cells and a significant decrease in tissue somatostatin. In a multicenter trial, patients with bleeding peptic or stress ulcers were treated with somatostatin or cimetidine plus pirenzepine. Results were favorable to the former substance on account of the time required to stop the hemorrhage and the demands for blood replacement. Thus, medical management of bleeding ulcers with somatostatin may represent an alternative to more radical surgical intervention. PMID- 2900187 TI - Prevention of pancreatic reactions by bolus somatostatin administration in patients undergoing endoscopic retrograde cholangio-pancreatography and endoscopic sphincterotomy. AB - Mild pancreatitis is a common complication of endoscopic retrograde cholangio pancreatography (ERCP) and endoscopic sphincterotomy. Knowing that a bolus injection of natural somatostatin (SRIF) dramatically reduces pancreatic secretion, a study was conducted in 33 subjects undergoing invasive diagnostic procedures. A placebo (n = 16) or SRIF (n = 17; 4 micrograms/kg) were injected before cannulation. Enzymatic rise was observed in 16 (94%) subjects receiving placebo and in 8 (50%) injected previously with SRIF. In the former group 65% reported abdominal pain whereas only 19% had this complaint in the SRIF series. Results suggest that a bolus injection of SRIF may attenuate pancreatic irritation caused by diagnostic procedures or sphincterotomy. PMID- 2900188 TI - Size changes of a growth hormone- and prolactin-producing adenoma during and after sandostatin treatment. AB - A 46-year-old woman with acromegaly and marked hyperprolactinemia was treated chronically with sandostatin (50 micrograms b.i.d. up to 100 micrograms t.i.d.). Plasma growth hormone (GH) was reduced by 90% of basal values and prolactin (PRL) dropped from initially 204 to 74 ng/ml. Serial CAT scans detected a volume reduction of the pituitary adenoma of 46.7%, but discontinuation of therapy was followed by re-expansion of the tumor. Tissue collected at transsphenoidal adenomectomy was examined by immunohistology and found positive for both GH and PRL. This characteristic would explain the dual hormonal response to the specific GH inhibitor sandostatin. PMID- 2900189 TI - Long-term management of acromegaly with sandostatin. AB - The present report illustrates the effectiveness of a long-acting somatostatin analog, SMS 201-995 (Sandostatin), in the chronic treatment of acromegaly. Daily doses of 50-300 micrograms were administered subcutaneously to 37 patients. Gradual dose increments induced a progressive GH decrease accompanied by a parallel reduction in plasma somatomedin C concentrations. There was a concomitant amelioration of clinical signs and symptoms throughout the investigational period. No escape phenomenon or tachyphylaxis was observed. It is concluded that chronic therapy with SMS 201-995 represents a promising medical alternative for the treatment of active acromegaly. PMID- 2900190 TI - Somatostatin analog treatment of acromegaly: new aspects. AB - Ten acromegalics received daily doses of 200-300 micrograms of a long-acting somatostatin analog, SMS 201-995 (Sandostatin, SMS), for an average of 64 weeks. Basal mean GH values of 44 +/- (SE) 7.8 ng/ml had fallen into the normal range at the end of the observation period (mean 64 weeks). This effect was accompanied by a substantial drop in somatomedin-C values. Reduction of pituitary tumor size could be documented in 3 of 6 patients. Whereas SMS did not affect high plasma PRL in 4 microprolactinoma patients, lactotrophs turned sensitive to this agent in mixed GH/PRL tumors. In a comparative study between SMS and bromocriptine, the former normalized circulating GH in 10 of 17 acromegalics in an acute trial, whereas bromocriptine was effective in only 5. A combination of both substances was effective in 2 of 3 patients who were insensitive to single drug administration. Cultures of GH-secreting tumor cells showed a statistically significant hormone decrease in the medium when exposed to SMS. However, in some instances, a diminution of the GH contents of the tumor cells was also observed, presumably as the basis for intracellular breakdown and clinical tumor shrinkage. PMID- 2900191 TI - Somatostatin analogs in the management of gastrointestinal tumors. AB - Experience with SMS 201-995 (Sandostatin), a somatostatin analog, in the treatment of endocrine active gastrointestinal tumors is reviewed. Best immediate results were obtained in vipomas and insulinomas but a scape phenomenon was frequently observed. A positive and persistent effect was recorded in a case of nesidioblastosis. It was striking that good clinical control could be obtained in some instances despite insufficient suppression of hormone secretion by the tumor. This finding suggests peripheral actions of somatostatin and SMS independently of its primary effect on hormone release. PMID- 2900192 TI - Treatment of inappropriate secretion of thyrotropin with somatostatin analog SMS 201-995. AB - Inappropriate thyrotropin secretion (IST) may originate from either neoplastic disease (nIST) or non-neoplastic resistance to thyroid hormone (nnIST). An inhibitory effect of somatostatin on TSH secretion has been documented. In an attempt to elucidate the possible therapeutic effect of this peptide on nIST and nnIST, a study was conducted in 7 such patients. Sandostatin (SMS 201-995) was administered in daily doses of 100 micrograms for several days to 1 month. Four patients with nIST responded with a fall in circulating TSH as well as alpha subunit with concomitant normalization of free thyroxine and clear symptomatic improvement. In the 3 nnIST patients this effect was considerably less apparent and a partial TSH escape was observed on long-term treatment in 2 cases. The importance of somatostatin and its analogs in the management of thyroid malignancy is stressed. PMID- 2900194 TI - Somatostatin. Recent advances in basic research and clinical applications. An international symposium of the European Neuroendocrine Association. Madrid, October 7-8, 1986. Proceedings. PMID- 2900193 TI - Influence of somatostatin and growth hormone-releasing factor on behavior. Clinical and therapeutic implications in neuropsychiatric disorders. AB - Administration of hypothalamic peptides has been reported to induce behavioral changes and to modify neurological functions such as locomotor activity and learning. Somatostatin (SS) and growth hormone-releasing factor (GRF) exert opposite effects on anterior pituitary secretion. Similarly, at the central nervous system (CNS) level, SS and GRF display antagonistic actions on behavioral parameters. The authors were able to confirm these effects in male Wistar rats by means of a computerized electronic maze measuring locomotor activity and learning. SS concentration is reduced in specific areas of the CNS in patients with late onset of senile dementia of the Alzheimer's type (SDAT). In early onset SDAT a GRF test elicits a growth hormone response much greater than that observed in normal controls of the same age or in patients with late onset SDAT. Thus, administration of GRF to patients with early onset SDAT has been followed by a significant improvement in locomotion, appetite, mental performance and social interaction. A possible therapeutic role of GRF in the management of patients with dementia remains to be explored. PMID- 2900195 TI - Somatostatin: a historical perspective. AB - Following the discovery and biochemical characterization of natural somatostatin its action profile has been thoroughly investigated. Although the name somatostatin was coined in virtue of its growth hormone release-inhibiting properties, a number of central and peripheral endocrine and paracrine actions have been ascribed to this peptide. Its inhibitory effect on a series of pituitary and gastrointestinal hormones has characterized somatostatin as a classical brain-gut hormone. Circulating and tissue levels of somatostatin and its possible physiological role are analyzed and clinical implications are drawn. PMID- 2900196 TI - Structure-function relationships of somatostatin analogs. AB - Objective of peptide chemistry has always been the production of analogues for clinical application. Advantages sought over natural peptides are (a) reduced molecular size; (b) prolonged biological half-life, and (c) enhanced specificity. After elucidation of the active core of somatostatin a number of analogues have been synthetized. Among them SMS 201-995, an octapeptide, was selected for further development because of its high potency and prolonged plasma clearance. Procedures extending the duration of action of somatostatin derivatives such as enhancement of lipophilicity and amino acid substitution are described, and factors influencing the specificity of such substances are succinctly analyzed. PMID- 2900198 TI - Somatostatin receptors in normal and tumoral tissue. AB - Somatostatin receptors have been visualized with autoradiography and characterised biochemically in various somatostatin target tissues, such as brain, pituitary, pancreas and gastrointestinal tract, where they are likely to mediate the somatostatin actions. With the same methods, somatostatin receptors have been detected also in tumors originating from somatostatin target tissues: high receptor incidence is found in GH-producing pituitary adenomas as well as in some hormone-producing gastrointestinal tumors. These tumors are often highly responsive to somatostatin analogs in vivo. Among brain tumors, meningiomas usually contain a high density of receptors, suggesting a novel function for somatostatin in the human meninges. Among other human tumors tested, prostate, ovarian and endometrial carcinomas were free of receptors whereas 3 out of 39 mammary tumors contained somatostatin receptors. PMID- 2900197 TI - Mechanism of action of somatostatin. AB - The chain of events leading to the manifestation of the biological action of somatostatin are described. Internalization is mediated by cytoskeletal proteins in the presence of calmodulin. Transduction of the somatostatin message at the membrane level takes place through inhibition of cyclic AMP accumulation and blockade of cytosol calcium increases. The influence of central and peripheral factors upon these processes is discussed and the importance of the Ni/Ns components is stressed. Thus, somatostatin also suppresses phosphoinositide turnover and stimulates soluble phosphodiesterase, thus reinforcing its negative effect on cyclase generation. PMID- 2900199 TI - Somatostatin as a physiological regulator of pulsatile growth hormone secretion. AB - Somatostatin plays an important role in the regulation of the episodic and ultradian rhythm of growth hormone (GH) secretion. Passive immunization of rats with specific antibodies to the 14 and 28 amino acid sequences caused a significant GH elevation. The fact that somatostatin antiserum was unable to block episodic GH surges indicates that this hormone's release must be regulated by a dual mechanism. Indeed, GH-releasing factor (GRF) seems to be instrumental in the maintenance of pulsatile GH secretion. Moreover, exogenous GRF induced a further GH increase predominantly during the period of active secretion. Neutralization of endogenous somatostatin eliminated this time-dependent effect, indicating that this peptide blocks periodical spontaneous GH release. Food deprivation and changes in glucose homeostasis virtually obliterate the ultradian GH rhythm. In this context, peripheral somatostatin seems to play an important role. Also the central GRF/somatostatin interplay is responsible for a short-loop feedback control on pituitary somatotrops. PMID- 2900200 TI - Physiological significance of gastrointestinal somatostatin. AB - Somatostatin participates in the regulation of nutrient entry from the intestinal tract into the circulation. Thus, dietary fats and proteins may elicit significant increases of gastropancreatic somatostatin. Regulation of postprandial somatostatin secretion may occur via neural, hormonal and humoral factors. This peptide, in pharmacological doses, inhibits virtually all gastrointestinal exo- and endocrine functions as well as local motor activity. Neutralization of endogenous circulating somatostatin with specific antiserum is followed by increases in GH and enteroglucagon, augmenting also the postprandial rise of gastrin, insulin and pancreatic polypeptide. Somatostatin deficiency can be observed in obese subjects with hyperinsulinism. Concomitant elevation of insulin and gastrin levels can be antagonized by exogenous somatostatin. These findings confirm the importance of somatostatin as a peripheral regulator in experimental and human biology. PMID- 2900201 TI - Somatostatin structure-activity studies in the stomach. AB - Somatostatin may inhibit gastric exocrine functions independent of blockade of gastrin secretion. In order to further investigate this suppressive effect, somatostatin derivatives were injected to cats bearing a cannulated gastric fistula under pentagastrin stimulation. Results showed that somatostatin-14 was more potent than somatostatin-28 in this particular model. Analogues with substituted residues exhibited a variable spectrum of actions on hormone release and gastric function. A cyclic pentapeptide was deprived of gastric or GH inhibitory properties whereas the related peptide with a benzyl-protecting group on Thr was only devoid of gastric effect. The octapeptide SMS 201-995 was described as a potent inhibitor of gastric secretion in comparison with natural somatostatin in rats and also in humans, but was unable to induce maximal suppression of acid output in the cat model. Differences in gastric effect of different derivatives could be explained on the basis of binding to a selective subset of receptors, since at least two binding sites have been identified in the stomach mucosa. Serial studies with short cyclic somatostatin should help to establish a clear relationship between peptide structure and inhibition of gastric secretion. PMID- 2900202 TI - Hormonal and nonhormonal cytoprotective effect by somatostatins. AB - Beside its known hormonal activity, somatostatin exerts cytoprotective action. Thus, its favorable effect on the course of experimental pancreatitis, liver and lung lesions, and gastric ulcerations cannot be explained solely on the basis of hormone-mediated mechanisms. Cytoprotection is only observed when somatostatin is administered prior to toxin exposure or tissue damage, and the structure/activity of the substance is important in determining this effect. Thus, the non-hormonal biological effects of somatostatin can be summarized as follows: (a) Natural somatostatin-14 has been shown, in addition to its full endocrine effect, to block the uptake of toxic substances into liver cells. (b) Analogues with superactive cytoprotection may be devoid of endocrine activity. In turn, this effect is commonly found in the low-molecular derivatives. (c) Although the mechanism leading to tissue protection has not been clarified, stabilisation of cell membranes may play a role as well as changes in the aminoacid sequence. PMID- 2900203 TI - Measurement of somatostatin. AB - Biological activity of somatostatin can be altered by modifications in the amino acid sequence. Thus, a number of bioassays have been developed in order to measure the potency and specificity of analogues and heterogeneous molecular forms of somatostatin. These procedures may assist in the estimation of somatostatin contents of tissue extracts but measurements in blood are limited by the presence of other substances masking the biological response to somatostatin. Recently, radioimmunoassay procedures have been developed and their usefulness in experimental and clinical medicine is reviewed. PMID- 2900204 TI - Clinical applications of somatostatin. AB - Because of its wide distribution in the organism, natural somatostatin (SRIF) demonstrates an ample spectrum of actions, involving mainly the central neuroendocrine system and the enteropancreatic area. In the former, this peptide may find its field of application in conditions characterized by excessive GH, TSH or ACTH secretion, depending on the central or peripheral cause of the inappropriate hormone control. The inhibitory effect of SRIF on gastrointestinal and pancreatic hormones may be useful in the management of tumors originating in this system and also in the treatment of inflammatory processes such as pancreatitis, in malignant diarrhea, and in gastrointestinal bleeding. A complex action of SRIF and its derivative on insulin release and glucose homeostasis may offer some advantages in the control of unstable diabetes. Dampening of organic functions in the upper digestive tract may also render SRIF and its analogues useful in the exploration of the gallbladder, gastric and pancreatic functions. The effect of such peptides on tissue growth and on the regulation of blood pressure are the subject of present investigations. Cytoprotection, an interesting aspect of SRIF application, is discussed elsewhere in this compendium. Finally, some comments on the possible use of SRIF as an additive to the conventional treatment of burns and sepsis close this review. PMID- 2900205 TI - Effect of a long-acting somatostatin derivative SMS 201-995 (sandostatin) on glucose homeostasis in type I diabetes mellitus. AB - The infusion of natural somatostatin (SRIF) has been able to partially correct postprandial hyperglycemic reactions in insulin-dependent diabetes mellitus (IDDM). SMS 201-995 (Sandostatin) is a long-acting derivative with a growth hormone-suppressive effect 10-60 times more potent than the native peptide. The effect of SMS 201-995 (50 micrograms s.c.) on glucose control by exogenous insulin has been documented in a series of type I diabetics after stabilization of blood sugar by an artificial pancreas. Inhibition of counterregulatory mechanisms significantly diminished the postprandial hyperglycemia, and insulin requirements, both total and 2 h after meals, were markedly decreased. Also the effect of a single s.c. injection of 100 micrograms SMS 201-995 on the dawn phenomenon in a patient with poorly adjustable diabetes was investigated. The glucose escape observed during the control night was blocked by SMS 201-995. Thus, the stabilizing action of this peptide on postprandial and nocturnal hyperglycemia in unstable diabetes warrants further studies. PMID- 2900206 TI - Preliminary experience on treatment of insulin-dependent diabetes mellitus with a long-acting somatostatin analogue (L363,586). AB - L363,586 is a potent, long-acting, somatostatin derivative. Intravenous and intranasal administration to diabetic subjects was effective in reducing both fasting and postprandial hyperglycemia. Also in patients stabilized on a closed loop insulin infusion device, the intranasal administration of L363,586 was able to improve the glucose imbalance known as dawn phenomenon. Therefore, this analogue associated to standard insulin replacement could be useful in the control of unstable diabetes. PMID- 2900207 TI - Effects of somatostatin in patients with portal hypertension. AB - Portal hypertension is a common complication of chronic liver disease. Conventional therapy consists of surgery and palliative measures for the hemodynamic problem. It has been recently reported that somatostatin may reduce portal pressure without altering the systemic circulation and so reducing hepatic blood flow. This peptide also causes a significant fall in azygos circulation in patients with esophageal varices. The mechanism of this effect is unclear although suppression of intestinal vasodilating hormones and of glucagon have been claimed to play a role. Comparative clinical studies have shown somatostatin to be superior to the standard vasopressin treatment. Recent findings suggest that the efficacy of somatostatin can be increased by administering this peptide in repeated intravenous bolus injections. New derivatives, specially long-acting peptides, may eventually prove beneficial in the chronic treatment of this complication. PMID- 2900208 TI - C-cell hyperplasia in thyroid tissue adjacent to follicular cell tumors. AB - An immunohistochemical study was conducted on the number and distribution of C cells in the nonneoplastic thyroid tissue adjacent to tumors of follicular cell origin. It consisted of 49 cases, of which 25 were papillary carcinomas, 22 were follicular adenomas, and 2 were follicular carcinomas. Twenty normal adult thyroids from the Broward's Medical Examiner's morgue served as controls. In 17 of the 49 cases (34.6%), there was a statistically significant increase in the number of C-cells in the normal-appearing thyroid tissue adjacent to follicular cell tumors, with at least 50 C-cells in one low power field, while only one of 20 normal thyroids had a similar number of cells. (P = .02; chi 2 = 5.05). In two tumor cases there were more than 100 C-cells in several low power fields with formation of small C-cell nodules similar to those described in the type II Multiple Endocrine Neoplasia Syndrome (MEN). It was concluded that the nonneoplastic thyroid tissue adjacent to 34.6% of tumors with follicular cell phenotypes contains significantly more C-cells than those present in normal adult thyroids. The possible pathogenesis and clinical significance of these findings are discussed. PMID- 2900209 TI - Factor XIIIa and the classic histiocytic markers in malignant fibrous histiocytoma: a comparative immunohistochemical study. AB - Fifteen cases of malignant fibrous histiocytoma (MFH) and 79 cases of differential-diagnostically related soft tissue tumors were evaluated for immunoreactive cells for the subunit A of factor XIII (F-XIIIa) in comparison with the staining obtained by the classic histiocytic markers: lysozyme, alpha 1 antitrypsin (AAT) and alpha 1-antichymotrypsin (AACT). Ubiquitous and focal staining patterns were distinguished. Only three cases of MFH were characterized by an ubiquitous positive reaction for AAT and AACT, in contrast to the obligatory positive staining of MFH for F-XIIIa. This low ratio is probably related to the high proportion of predominantly fibroblastic and myxoid types of MFH (11/15). In the three cases of MFH characterized by ubiquitous positive reactions for both antiproteases and for F-XIIIa, the frequency of positive cells for AAT and AACT exceeded that for F-XIIIa. Thus, the positive cells for antiproteases and those for F-XIIIa represent different levels of fibro histiocytic differentiation; the F-XIIIa-positive cells are fibro-histiocyte precursors. F-XIIIa-positive stromal cells are present in the normal mesenchyme, but their significance is unknown. The fact that these cells are a constant feature of MFH argues for a histiocytic pathway of their differentiation. The ubiquitous presence of F-XIIIa-positive cells in MFH distinguishes them from the histologically similar soft tissue tumors. However, the focal presence of F-XIIIa positive cells indicate only a host response to an unspecified tissue injury that may occur in all kinds of soft tissue tumors. PMID- 2900210 TI - Lymph node enlargement in patients with unsuspected human immunodeficiency virus infections. AB - The histologic findings in lymph nodes were used to identify eight patients, who are not in a high-risk group, with human immunodeficiency virus (HIV) infection. In order to determine the specificity of these findings, the histologic and clinical findings in these patients were compared with the histologic and clinical findings in 40 patients whose lymph nodes exhibited reactive follicular hyperplasia and who received biopsies before 1981. While a definitive diagnosis of HIV infection cannot be made from the histologic changes in lymph nodes because the organisms cannot be identified, our findings indicate that HIV infection can be suggested, and appropriate testing warranted, when marked reactive follicular hyperplasia with mononuclear cells (and a small number of neutrophils) in parafollicular sinuses is found in a patient with unexplained lymph node enlargement at two or more noncontiguous, noninguinal sites for several months, with or without systemic symptoms. PMID- 2900211 TI - An autopsy case of human T-lymphotropic virus type I-associated myelopathy. AB - This report describes the first autopsy case of human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM). The disease mainly affected the spinal cord, particularly the lateral and anterior columns, where loss of myelin and axon was observed. The changes were bilateral and occurred mainly along the tract. Perivascular and parenchymal infiltration with lymphocytes and macrophages, as well as astrocytosis, were observed in the white and grey matters of the spinal cord. Blood vessels in the spinal cord and in the subarachnoid space of the spinal cord showed hyalinoid thickening of media and adventitia associated with infiltration of lymphocytes. These findings are similar to those of tropical spastic paraparesis (TSP). PMID- 2900214 TI - Restriction fragment length polymorphisms detected by anonymous DNA probes mapped to defined intervals of human chromosome 16. AB - Three anonymous DNA probes ACH207, ACH224, and ACH202, isolated from a flow purified chromosome 16 library and mapped to defined intervals of human chromosome 16, detected restriction fragment length polymorphisms (RFLPs). The RFLPs were of simple two allele types. The ACH207 (D16S4) probe detected a TaqI and an MspI RFLP with polymorphism information content (PIC) values of 0.30 and 0.27; the ACH224 (D16S5) probe detected an RsaI RFLP, PIC value of 0.34; and the ACH202 (D16S4) probe detected an XbaI RFLP, PIC value of 0.22. PMID- 2900213 TI - Analysis for linkage between F13A and three chromosome 6 marker loci: evidence for 6pter:F13A:HLA:GLO1:cen gene order. AB - The results of the present study provide independent support for F13A:HLA linkage and refine the F13A:HLA and F13A:GLO1 linkage relationships. Analysis of the corresponding recombination fractions for the total paternal F13A:HLA and F13A:GLO1 peak lod scores (z) indicates a locus order of 6pter:F13A:HLA:GLO1:cen. Lod scores between F13A and PLG, a locus recently assigned to chromosome 6, exclude close linkage between these loci. PMID- 2900212 TI - Polymorphism of MHC class III genes: definition of restriction fragment linkage groups and evidence for frequent deletions and duplications. AB - The loci for the complement proteins BF and C2 and the two loci for C4 are closely linked to one another, as are the duplicated steroid 21 hydroxylase (21 OHase) genes to the C4A and C4B loci. The alleles of these four loci occur in specific combinations termed "complotypes". We have studied the gene frequencies of their different products in the Lebanese population and compared these values with those found in other populations. We observed a novel complotype (S B 4 6) in one family and a complotype with a so far undescribed variant of the C4A locus. Using several restriction fragment length polymorphisms (RFLPs), we have defined restriction fragment linkage groups. The combined use of C4 and 21-OHase probes allowed us to detect different types of deletions and duplications at these loci in the Lebanese population. PMID- 2900215 TI - Isolation of the gene for Duchenne muscular dystrophy. PMID- 2900216 TI - Pharmacokinetics of paracetamol, diclofenac and vidarabine during plasma exchange. AB - In order to establish guidelines for prescribing drugs in patients treated with plasma exchange (PE), we studied the pharmacokinetics of paracetamol (5 patients), diclofenac (4 patients) and vidarabine (3 patients) during one or several PE. Results were compared with those obtained without PE. Diclofenac and paracetamol were chosen because they presented different volume distribution and protein binding characteristics. Vidarabine was studied because we use it for the treatment of patients with polyarteritis nodosa related to hepatitis B virus. Diclofenac (100 mg) and paracetamol (1000 mg) were given 1 hour before PE. Samples were obtained 60 and 30 min before PE, every 15 min during PE and hourly for 2 hours after the end of PE. Vidarabine was given in continuous infusion, 15 mg/kg/d during the first week of treatment and 7.5 mg/kg/d during subsequent weeks. Samples were obtained before PE, 3 times during PE and every 30 min for 4 hours after the end of PE. Paracetamol, diclofenac, vidarabine and hypoxanthine arabinoside were assayed by high performance liquid chromatography. During each PE 60 ml/kg were removed and replaced by albumin. We found that 17% of diclofenac, 4.3% of paracetamol and 4.9% of vidarabine were removed during each session. Plasmapheresis clearance was 51% of plasma clearance for diclofenac, 15% for paracetamol and 10% for vidarabine. Drugs which are mainly removed during PE are those which are bound to proteins with a small distribution volume. Those drugs, such as diclofenac, must be administered after the end of each PE session. Drugs which present a large distribution volume and low protein binding can be given before the session. Vidarabine can be administered during PE without loss of effectiveness due to drug removal. PMID- 2900218 TI - Pharmacotherapy of the aggressive adult patient. PMID- 2900217 TI - The electrophysiologic properties of esmolol, a short acting beta-blocker. AB - Although beta-blockers have established efficacy in treating ventricular ectopy and PSVT, their applicability for acute antiarrhythmic interventions in patients with organic heart disease or COPD, is frequently limited by negative inotropic or bronchospastic side effects. The development of an ultrashort acting beta blocker with rapid reversibility of its side effects would widen their applicability. Therefore, we tested the electrophysiologic properties of such a new short acting beta-blocker, esmolol, in 14 patients (10 with organic heart disease) with a mean EF of 47.6 +/- 17%, undergoing standard clinical electrophysiologic studies for various indications. Like most other beta blockers, esmolol's major direct effects were on sinus node function and AV nodal conduction characteristics; significantly prolonging sinus cycle length, cycle length to Wenckebach and AH interval in sinus rhythm and at a paced cycle length of 600 ms. In contrast to most other beta-blockers, following termination of its infusion, esmolol shortened parameters of sinus node function and AV nodal refractoriness, with respect to the control values, suggesting a possible rebound phenomena. These effects occurred within 5 min of terminating the intravenous drug infusion. Esmolol had no significant effect on systolic blood pressure, electrocardiographic intervals and had rare adverse reactions. We conclude that esmolol is an ultra-short acting beta-blocker, with typical direct electrophysiologic effects on sinus node and AV nodal function, and a possible rebound phenomena following its discontinuation that may make it particularly suited to acute antiarrhythmic interventions in patients susceptible to adverse beta-blocker side effects. PMID- 2900220 TI - Recent research in neuroimmunomodulation: some highlights of the second international workshop, and some clinical implications of behavioral immunology. PMID- 2900219 TI - Neuroleptic-mediated hypothalamic deregulation of central insulin and peripheral glucose metabolism in tardive dyskinesia: a hypothesis. AB - In the following communication we discuss evidence that impaired peripheral and central glucose and insulin metabolism may be significant in the pathophysiology of neuroleptic-induced tardive dyskinesia. Such an association between alterations in glucose metabolism and pathophysiology of tardive dyskinesia may open new avenues in the prevention and pharmacological management of this often therapy-resistant chronic neurological disorder. PMID- 2900221 TI - Dopaminergic stimulation of the immune reaction: interaction of serotoninergic and dopaminergic systems in neuroimmunomodulation. PMID- 2900222 TI - [Carcinoid syndrome with a course of more than 10 years]. PMID- 2900223 TI - [Receptors for neurotransmitters and psychiatric diseases]. PMID- 2900224 TI - Gamma-glutamyltranspeptidase isoenzyme forms and lipoproteins in normal and pathological sera. AB - The molecular nature of serum (from normal subjects and from patients affected by various hepatobiliary diseases) gamma-glutamyltranspeptidase (GGT) isoenzymes has been studied by selective lipoprotein precipitation. Some fractions co precipitate with LDL + VLDL (pre-beta-, beta-, beta/gamma-, gamma-, and dep-GGT fractions) or with HDL (partial precipitation of alpha 1-GGT in cirrhosis). Alpha 1-GGT + alpha 2-GGT in normal subjects, and Alb-GGT did not precipitate with either of the precipitation treatments. Total GGT and its isoenzymes were stable at 4 degrees C and at -20 degrees C for at least 20 days, with the exception of Alb-GGT which at -20 degrees C decreased by 20%. The percentage of GGT associated with LDL + VLDL appeared to be a possible marker to discriminate liver tumors from cirrhosis. A cut-off value of 20 U/L of this marker yielded a diagnostic sensitivity of 87% and a diagnostic specificity of 85%. PMID- 2900225 TI - Pisa syndrome. Report of a case. AB - Very few cases of Pisa syndrome have been reported. The syndrome consists of dystonic symptoms, namely, tonic flexion of the trunk to one side and its slight rotation. It appears to be a side effect of prolonged antipsychotic therapy. We report on a case of Pisa syndrome in which withdrawal significantly improved the dystonic symptoms. However, a severe exacerbation of schizophrenic symptoms required the immediate resumption of neuroleptic therapy which was followed by the reappearance of dystonic symptoms. Associated anticholinergic medication led to only a slight improvement. PMID- 2900226 TI - Effect of chlorpromazine (CPZ) on cholecystokinin-induced gallbladder contraction: the role of calcium. AB - Smooth muscle contraction is initiated by a rise in intracellular calcium, which binds to calmodulin resulting in myosin phosphorylation. CPZ impairs smooth muscle contraction by either interfering with calcium influx at low concentrations (less than 1.25 x 10(-5) M) or inactivating calcium-calmodulin at higher levels. This chlorpromazine effect was used to determine if gallbladder agonists act through different intracellular mechanisms. Guinea pig gallbladders were mounted in an organ bath and auxotonic contractions induced by bethanechol, KCl and the octapeptide of cholecystokinin (CCK). Bethanechol and KCl-induced contractions were profoundly inhibited by 1.25 x 10(-5) M CPZ throughout the dose response curve. In contrast, CPZ did not affect CCK-mediated contractions at CCK concentrations less than 5.7 x 10(-8) M. At maximal CCK doses (3 x 10(-7) M), CPZ had only a modest inhibitory effect of 20%, compared with tension losses of 62 and 80% for bethanechol and KCl, respectively. This inhibition with high-dose CCK was offset by increasing extracellular calcium in the organ bath. The resistance of CCK to CPZ inhibition at low doses within the physiologic range implies that CCK acts independently of extracellular Ca2+ unlike the other agonists. Higher CPZ concentrations, greater than or equal to 1.25 x 10(-4) M, markedly suppressed CCK throughout the dose-response curve. Cholecystokinin may act via myosin phosphorylation, but unlike other agonists any rise in cytoplasmic calcium likely originates from an intracellular site. PMID- 2900227 TI - Binding of mouse red blood cells (MRBC) by human thymocytes: augmentation of rosette formation by phospholipase C treatment. AB - The formation of rosettes with MRBC is not an exclusive property of chronic lymphocytic leukemia cells and of human B-lymphocytes. Human thymus cells and the HD-MAR T-cell line were also found to be capable of forming rosettes with MRBC. The binding of MRBC by thymocytes differed from that of sheep (SRBC), rabbit (RRBC) and human (HRBC) erythrocytes by a number of parameters: monoclonal antibodies against the E-receptor inhibited the attachment of SRBC, RRBC, and HRBC, but not of MRBC to thymus cells. The presence of EDTA had the opposite effect, abrogating only the attachment of MRBC to thymus cells but not of RBC from the other sources. Exposure of thymus cells to pronase eliminated their capacity to bind SRBC, RRBC, and HRBC, but only slightly inhibited the attachment of MRBC. Treatment with Vibrio cholerae neuraminidase enhanced the formation of rosettes with SRBC, RRBC, and HRBC, but had no effect on the formation of rosettes with MRBC. Exposure of thymus cells and of the HD-MAR cells to phospholipase C enhanced the proportion of rosettes formed with MRBC, but had no effect on the binding of other RBC. Treatment with either phospholipase A2 or phospholipase D had no such effect. The binding of MRBC by Raji cells was not increased by phospholipase C treatment. The present study indicates that the binding of MRBC by human thymus cells is mediated by receptors distinct from those involved in the binding of SRBC, RRBC, and HRBC and also from those mediating the binding of MRBC to human B-cells. PMID- 2900228 TI - HTLV-1 seroconversion in a 56-year-old Japanese woman undergoing chemotherapy for acute nonlymphocytic leukemia. PMID- 2900229 TI - Synaptic communication between somatostatinergic axons and growth hormone releasing factor (GRF) synthesizing neurons in the arcuate nucleus of the rat. AB - Growth hormone (GH) production of the anterior pituitary gland is controlled by inhibiting and releasing hormones that are synthesized in the diencephalon. In order to elucidate the possible interrelationships between somatostatin and growth hormone-releasing factor (GRF) synthesizing neurons at the hypothalamic level, immunocytochemical double labelling studies were performed on sections containing the arcuate nucleus (ARC) of the rat. Somatostatin producing neurons were located in the dorsomedial part of the ARC, while somatostatin immunoreactive (IR) axons were found in the ventro-lateral part of the nucleus, an area containing GRF-synthesizing cells. The use of the dual antigen localization technique revealed the approach and juxtaposition of somatostatin containing axons to dendrites and cell bodies of GRF-synthesizing neurons. At the light microscopic level, several somatostatinergic axon varicosities were clustered around single GRF-synthesizing cells. Ultrastructural analysis of the ventro-lateral part of the ARC showed that (i), somatostatinergic axons established synaptic connections (ii), GRF-producing neurons received axons terminals on their somata and dendrites and (iii), somatostatin-IR axons formed asymmetric synaptic specializations with both dendrites and somata of GRF synthesizing neurons. These morphological findings indicate that the hormone production and release of hypophysiotrophic GRF-IR neurons can be influenced by the central somatostatin system via direct synaptic mechanisms. The data support the concept, that the interaction of inhibiting and releasing hormones, which determines responses of the pituitary target cells, may take place also at the hypothalamic level. PMID- 2900230 TI - Auditory evoked potentials as possible predictors of outcome in schizophrenic outpatients. AB - As part of a follow-up study on long-term neuroleptic treatment, 36 schizophrenic out-patients under neuroleptic treatment were studied in an 'auditory oddball' event-related potential paradigm after a 3-month stabilization phase following clinical discharge. In the first cross-sectional analysis, we evaluated the influences of age and gender and tried to find auditory evoked potential (AEP) variables, which might be promising as potential predictors of the course of illness. Compared with healthy age-matched controls, the patients showed smaller N1/P3-amplitudes. Males and females showed only minor AEP-differences, the amplitude N1/P2 being slightly higher in females. Age correlated positively with the latency P3 and negatively with the latency P2R. The interpeak latency P3-P2R showed the highest correlation with age. Test/re-test reliability was measured and variables with r less than 0.60 were rejected. The amplitudes N1/P2 and N1/P3 showed the highest test/re-test correlations. The more severely disturbed patients (global assessment scale [GAS]-score less than 65) had shorter interpeak latencies P2F-N1F than the less disturbed patients (GAS greater than or equal to 65). Patients with a high rate of relapse tended to have shorter interpeak latencies P2F-N1F than patients with low rates of relapse. Our results indicate that the interpeak latency P2F-N1F has an acceptable test/re-test reliability (C3: r = 0.72; C4: r = 0.80) and is related to clinical variables characterizing the course and outcome of illness. This leads to the hypothesis that a short interpeak latency, P2F-N1F, might be a predictor of poor prognosis. PMID- 2900231 TI - Serum soluble interleukin-2 receptor levels in patients with adult T-cell leukemia and human T-cell leukemia/lymphoma virus type-I seropositive healthy carriers. AB - Using an enzyme-linked immunosorbent assay (ELISA) technique, we measured the soluble interleukin 2 receptor (s-IL-2R) levels in the sera of patients with adult T-cell leukemia (ATL) in Japan. The s-IL-2R levels in the sera of the ATL patients were markedly higher (range 540-310, 400 U/ml, mean +/- SD = 62,800 +/- 81,000 U/ml, n = 42) than those in normal individuals (range 42-950 U/ml, mean +/ SD = 322 +/- 198 U/ml, n = 35, P less than 0.01). The patients with acute-type or lymphoma-type ATL had high s-IL-2R levels (range 11,900-310,400 U/ml, mean +/- SD = 110,340 +/- 370 U/ml, n = 15; range 26,400-214,400 U/ml, mean +/- SD = 90,170 +/- 59,040 U/ml, n = 7, respectively). All of the patients with hypercalcemia (Ca greater than 10 mg/dl) or elevated serum LDH levels (LDH greater than 500 IU/liter) also had s-IL-2R levels above 10,000 U/ml. The high s IL-2R levels in the sera of ATL patients indicate abnormal IL-2 receptor production and its release from the leukemic cells in vivo. Thus, the serum s-IL 2R level may be a sensitive and useful marker to monitor the total amount of tumor cells in ATL, especially in the lymphoma type. We next examined the serum s IL-2R levels in human T-cell leukemia/lymphoma virus type-I (HTLV-I) seropositive healthy carriers to investigate whether there might be abnormal IL-2 receptor expression in such individuals. However, there was no statistically significant difference between the s-IL-2R level of 71 HTLV-I seropositive healthy carriers (range 65-880 U/ml, mean +/- SD = 394 +/- 212 U/ml) and that of 71 age- and sex matched normal individuals (range 33-950 U/ml, mean +/- SD = 357 +/- 224 U/ml) who lived in Okinawa Prefecture. PMID- 2900233 TI - Role of beta 2-adrenergic receptors on coronary resistance during exercise. AB - The effects of regional alpha- and specific beta 2-adrenergic receptor blockade on measurements of late diastolic coronary resistance (LDCR) and mean coronary blood flow velocity (CBFV) during exercise were examined in 14 conscious adult mongrel dogs. Specific beta 2-adrenergic receptor blockade (ICI 118.551) significantly decreased CBFV and increased LDCR by blockade of beta 2-vasodilator tone independent of alpha-adrenergic receptor-mediated tone and independent of altering myocardial metabolism. alpha-Adrenergic receptor blockade (phentolamine, 1 mg) significantly increased CBFV and decreased LDCR by blocking sympathetically mediated vasoconstrictor tone. There was no significant difference in the magnitude of response between alpha- and beta 2-adrenergic receptor blockade. These results demonstrate that alpha- and beta 2-adrenergic receptors have a significant and evidently equal influence on CBFV and LDCR during exercise. Four weeks of daily exercise and left stellate ganglionectomy (LSGx) prevented phentolamine-induced vasodilation but not ICI 118.551-induced vasoconstriction. This suggests that daily exercise and LSGx significantly decreased the alpha adrenergic receptor-mediated vasoconstrictor tone on the coronary circulation, resulting in an apparently greater role for the coronary vascular beta 2 adrenergic receptor on the control of CBFV and LDCR during exercise. PMID- 2900232 TI - Characterization and localization of beta-adrenergic receptors in control and cryptorchidized rat testis by in vitro autoradiography. AB - beta-adrenergic receptors were localized and characterized in control and cryptorchidized rats to investigate further their role in testicular function. Slide-mounted cryostat sections were incubated with [125I]cyanopindolol, a specific ligand for beta-adrenergic receptors. The subtypes were characterized by the displacement of [125I]cyanopindolol binding by practolol, which binds preferentially to the beta 1 subtype, and zinterol, which is preferential for beta 2 receptors. Labeling was detected by autoradiography, first by exposing sections to Ultrofilm (LKB) and second by dipping slides in NTB-2 Kodak photographic emulsion. The histologic distribution of receptors was analyzed by counting silver grains overlying the testicular structures. It was found that the vast majority of receptors were of the beta 2-subtype. In intact rats, the greatest density of receptors was found in interstitial cells, with some specific labeling over the seminiferous tubules. However, in cryptorchidized animals, the proportion of beta 2 receptors in tubules that contained mainly Sertoli cells appeared to be markedly increased. The results obtained suggest that catecholamines have multiple sites of action in the testis. PMID- 2900234 TI - Effects of beta-adrenergic agents in lungs of normal and air-embolized awake sheep. AB - It is unclear whether beta-adrenergic agonists or antagonists affect lung liquid and protein exchange by changing pulmonary hemodynamics or microvascular leakiness. In 23 unanesthetized, instrumented sheep with long-term lung lymph fistulas, we assessed the effect of the beta-agonist terbutaline or the beta antagonists propranolol, nadolol, and atenolol, all infused intravenously, on lung lymph flow under base-line conditions and during the acute lung injury caused by 4 h of venous air embolism. Under base-line conditions, neither beta stimulation nor blockade had any effect. During air embolism, terbutaline decreased pulmonary vascular resistance and lymph flow by 25%. Propranolol and nadolol (non-selective beta 1,beta 2-antagonists) but not atenolol (selective beta 1-antagonist) also decreased lymph flow by 22% on average. We favor the more conservative (hemodynamic) over the more liberal (altered permeability) explanation for our results. First, beta-stimulation clearly caused vasodilation, which lowered the pulmonary microvascular pressure at the site of injury. beta blockade caused changes similar to alpha-stimulation (J. Appl. Physiol. 62: 2147 2153, 1987). We therefore interpret the beta-blockade as unmasking pulmonary arterial alpha-receptors stimulated by the air-embolism injury, thus allowing vasoconstriction upstream to the site of injury. We do not believe the explanation of the beta-agent effects requires any modulation of lung microvascular leakiness by beta-adrenergic agents. PMID- 2900235 TI - Purification of the Escherichia coli type 1 pilin and minor pilus proteins and partial characterization of the adhesin protein. AB - Type 1 pili of Escherichia coli contain three integral minor proteins with apparent molecular weights (Mr) of 28,000 (28K protein), 16,500, and 14,500 attached to rods composed of Mr-17,000 pilin subunits (Hanson and Brinton, Nature [London] 322:265-268). We describe here an improvement on our earlier method of pilus purification, which gives higher yields and higher purity. Also reported are methods allowing fractionation of intact type 1 pili into rods of pure pilin and free minor proteins, as well as fractionation of the 28K tip adhesion protein from the 16.5K and 14.5K proteins. We have determined the amino acid composition and amino-terminal sequence of the adhesion protein. This sequence shows limited homology with the amino-terminal sequences of several E. coli pilins, including type 1. PMID- 2900236 TI - Genes encoding the alpha, gamma, delta, and four F0 subunits of ATP synthase constitute an operon in the cyanobacterium Anabaena sp. strain PCC 7120. AB - A cluster of genes encoding subunits of ATP synthase of Anabaena sp. strain PCC 7120 was cloned, and the nucleotide sequences of the genes were determined. This cluster, denoted atp1, consists of four F0 genes and three F1 genes encoding the subunits a (atpI), c (atpH), b' (atpG), b (atpF), delta (atpD), alpha (aptA), and gamma (atpC) in that order. Closely linked upstream of the ATP synthase subunit genes is an open reading frame denoted gene 1, which is equivalent to the uncI gene of Escherichia coli. The atp1 gene cluster is at least 10 kilobase pairs distant in the genome from apt2, a cluster of genes encoding the beta (atpB) and epsilon (atpE) subunits of the ATP synthase. This two-clustered ATP synthase gene arrangement is intermediate between those found in chloroplasts and E. coli. A unique feature of the Anabaena atp1 cluster is overlap between the coding regions for atpF and atpD. The atp1 cluster is transcribed as a single 7-kilobase polycistronic mRNA that initiates 140 base pairs upstream of gene 1. The deduced translation products for the Anabaena sp. strain PCC 7120 subunit genes are more similar to chloroplast ATP synthase subunits than to those of E. coli. PMID- 2900237 TI - Molecular characterization of the type 3 (MR/K) fimbriae of Klebsiella pneumoniae. AB - The expression of type 3 (MR/K) fimbriae by Klebsiella pneumoniae requires the production of at least four polypeptides with molecular masses of 20.5, 25, 34, and 78 kilodaltons. The genes encoding these polypeptides are located on a gene cluster 5,500 base pairs in length. The nucleotide sequence of the major fimbrial structural gene was determined, and its transcription was shown to initiate in vitro 157 base pairs upstream of the translational start site. The predicted amino acid sequence for the fimbrial subunit comprised 202 residues, including a signal peptide of 22 amino acids. Despite similarities in the organization of the gene cluster, the nucleotide and the amino acid sequence of the major fimbrial subunit revealed little agreement with other known fimbrial subunit sequences. PMID- 2900238 TI - Cloning and sequence of the gene encoding the major structural component of mannose-resistant fimbriae of Serratia marcescens. AB - Serratia marcescens US46, a human urinary tract isolate, exhibits mannose resistant hemagglutination and agglutinates yeast cells, thereby indicating that it has two types of adhesins. We constructed a cosmid library for the DNA of this organism and isolated DNA clones carrying genes for mannose-sensitive (MS) and mannose-resistant (MR) fimbriae. On introduction of the cloned genes into Escherichia coli K-12, MS and MR fimbriae were formed. These fimbriae were functionally and morphologically indistinguishable from those of S. marcescens. Subcloning of these gene clusters revealed that the genes encoding MS fimbriae reside on a 9-kilobase (kb) DNA fragment, while those encoding MR fimbriae are present on a 12-kb fragment. Transposon insertion and maxicell analyses revealed that formation of MR fimbriae is controlled by several genes which reside on the 9-kb fragment. The nucleotide sequence of smfA, the gene encoding the major structural component of MR fimbriae, revealed that this gene encodes a 174-amino acid polypeptide with a typical procaryotic signal peptide. The primary structure of the smfA product showed significant homology with the primary structure of the E. coli fimbrial subunit. PMID- 2900240 TI - Adenine nucleotides as allosteric effectors of pea seed glutamine synthetase. AB - The effects of adenine nucleotides on pea seed glutamine synthetase (EC 6.3.1.2) activity were examined as a part of our investigation of the regulation of this octameric plant enzyme. Saturation curves for glutamine synthetase activity versus ATP with ADP as the changing fixed inhibitor were not hyperbolic; greater apparent Vmax values were observed in the presence of added ADP than the Vmax observed in the absence of ADP. Hill plots of data with ADP present curved upward and crossed the plot with no added ADP. The stoichiometry of adenine nucleotide binding to glutamine synthetase was examined. Two molecules of [gamma-32P]ATP were bound per subunit in the presence of methionine sulfoximine. These ATP molecules were bound at an allosteric site and at the active site. One molecule of either [gamma-32P]ATP or [14C]ADP bound per subunit in the absence of methionine sulfoximine; this nucleotide was bound at an allosteric site. ADP and ATP compete for binding at the allosteric site, although ADP was preferred. ADP binding to the allosteric site proceeded in two kinetic phases. A Vmax value of 1.55 units/mg was measured for glutamine synthetase with one ADP tightly bound per enzyme subunit; a Vmax value of 0.8 unit/mg was measured for enzyme with no adenine nucleotide bound at the allosteric site. The enzyme activation caused by the binding of ADP to the allosteric sites was preceded by a lag phase, the length of which was dependent on the ADP concentration. Enzyme incubated in 10 mM ADP bound approximately 4 mol of ADP/mol of native enzyme before activation was observed; the activation was complete when 7-8 mol of ADP were bound per mol of the octameric, native enzyme. The Km for ATP (2 mM) was not changed by ADP binding to the allosteric sites. ADP was a simple competitive inhibitor (Ki = 0.05 mM) of ATP for glutamine synthetase with eight molecules of ADP tightly bound to the allosteric sites of the octamer. Binding of ATP to the allosteric sites led to marked inhibition. PMID- 2900239 TI - Isolation and characterization of Escherichia coli mutants that lack the heat shock sigma factor sigma 32. AB - The product of the Escherichia coli rpoH (htpR) gene, sigma 32, is required for heat-inducible transcription of the heat shock genes. Previous studies on the role of sigma 32 in growth at low temperature and in gene expression involved the use of nonsense and missense rpoH mutations and have led to ambiguous or conflicting results. To clarify the role of sigma 32 in cell physiology, we have constructed loss-of-function insertion and deletion mutations in rpoH. Strains lacking sigma 32 are extremely temperature sensitive and grow only at temperatures less than or equal to 20 degrees C. There is no transcription from the heat shock promoters preceding the htpG gene or the groESL and dnaKJ operons; however, several heat shock proteins are produced in the mutants. GroEL protein is present in the rpoH null mutants, but its synthesis is not inducible by a shift to high temperature. The low-level synthesis of GroEL results from transcription initiation at a minor sigma 70-controlled promoter for the groE operon. DnaK protein synthesis cannot be detected at low temperature, but can be detected after a shift to 42 degrees C. The mechanism of this heat-inducible synthesis is not known. We conclude that sigma 32 is required for cell growth at temperatures above 20 degrees C and is required for transcription from the heat shock promoters. Several heat shock proteins are synthesized in the absence of sigma 32, indicating that there are additional mechanisms controlling the synthesis of some heat shock proteins. PMID- 2900241 TI - Gene structure of the human mitochondrial adenosine triphosphate synthase beta subunit. AB - The mitochondrial ATP synthase beta subunit is encoded by a nuclear gene and assembled with the other subunits encoded by both mitochondrial and nuclear genes. As the next step in the analysis of the molecular mechanisms coordinating the two genetic systems, the gene for the human beta subunit was cloned, and its structure was determined. The gene contains 10 exons, with the first exon corresponding to the noncoding region and most of the presequence which targets this protein to the mitochondria. Eight Alu repeating sequences including inverted repeats were found in the 5' upstream region and introns. An S1 nuclease protection experiment revealed two initiation sites for the transcription. A typical TATA box was not present at about 30 base pairs upstream from either initiation site. Three CAT boxes (CCAAT) were found between the two initiation sites. In addition, one CAT box was found 41 base pairs upstream from the first initiation site. Two GC boxes (potential Sp1 binding sites) were located in the 5' upstream region, one of them linked to Alu repeating sequences. For determination of the promoter activity, fragments of various length from the 5' upstream region were fused to a chloramphenicol acetyltransferase gene and transfected into cultured cells. This experiment showed the existence of an enhancing, structure(s) for transcription between nucleotide -400 and -1100 in the upstream region. PMID- 2900242 TI - The molecular basis of retinoic acid action. Transcriptional regulation of tissue transglutaminase gene expression in macrophages. AB - Retinoic acid acts as an acute and specific inducer of tissue transglutaminase in mouse resident peritoneal macrophages. We have isolated cDNA clones for this enzyme and used them to demonstrate that this induction is due to the accumulation of tissue transglutaminase mRNA that occurs within minutes of exposure of macrophages to retinoic acid. The retinoic acid-induced increase in tissue transglutaminase mRNA is independent of concurrent protein synthesis and is due to an increased transcription of the tissue transglutaminase gene. Our results demonstrate that retinoic acid is capable of inducing acute transcriptional activation of gene expression in myeloid cells. PMID- 2900243 TI - Evidence for a reactive gamma-carboxyl group (Glu-418) at the herbicide glyphosate binding site of 5-enolpyruvylshikimate-3-phosphate synthase from Escherichia coli. AB - Incubation of 5-enolpyruvylshikimate-3-phosphate synthase, a target for the nonselective herbicide glyphosate (N-(phosphonomethyl)glycine), with 1-ethyl-3-(3 dimethylaminopropyl)carbodiimide in the presence of glycine ethyl ester resulted in a time-dependent loss of enzyme activity. The inactivation followed pseudo first order kinetics, with a second order rate constant of 2.2 M-1 min-1 at pH 5.5 and 25 degrees C. The inactivation is prevented by preincubation of the enzyme with a combination of the substrate shikimate 3-phosphate plus glyphosate, but not by shikimate 3-phosphate, phosphoenolpyruvate, or glyphosate alone. Increasing the concentration of glyphosate during preincubation resulted in decreasing the rate of inactivation of the enzyme. Complete inactivation of the enzyme required the modification of 4 carboxyl groups per molecule of the enzyme. However, statistical analysis of the residual activity and the extent of modification showed that among the 4 modifiable carboxyl groups, only 1 is critical for activity. Tryptic mapping of the enzyme modified in the absence of shikimate 3-phosphate and glyphosate by reverse phase chromatography resulted in the isolation of a [14C]glycine ethyl ester-containing peptide that was absent in the enzyme modified in the presence of shikimate 3-phosphate and glyphosate. By amino acid sequencing of this labeled peptide, the modified critical carboxyl group was identified as Glu-418. The above results suggest that Glu-418 is the most accessible reactive carboxyl group under these conditions and is located at or close to the glyphosate binding site. PMID- 2900244 TI - Site-directed mutagenesis of Petunia hybrida 5-enolpyruvylshikimate-3-phosphate synthase: Lys-23 is essential for substrate binding. AB - Chemical modification of Escherichia coli 5-enolpyruvylshikimate-3-phosphate synthase, a target for the nonselective herbicide glyphosate (N phosphonomethylglycine), with pyridoxal 5'-phosphate suggested that Lys-22 (equivalent to Lys-23 of the Petunia hybrida enzyme) is a potential active site residue (Huynh, Q. K., Kishore, G. M., and Bild, G. S. (1988) J. Biol. Chem. 263, 735-739). To investigate the possible role of this residue in the reaction mechanism, we have used site-directed mutagenesis to replace Lys-23 of the P. hybrida enzyme with 3 other amino acid residues: Ala, Glu, and Arg. Analysis of these mutant enzymes indicates that of these only the Lys-23 to Arg mutant enzyme is active; the other two replacements (Ala and Glu) result in inactivation of the enzyme. Two of the mutant enzymes (Lys-23 to Arg and Ala) were purified to homogeneity and characterized. The purified Lys-23 to Arg mutant enzyme is less sensitive than the wild type enzyme to pyridoxal 5'-phosphate. It showed identical Km values for substrates and a 5-fold higher I50 value for glyphosate in comparison with those from the wild type enzyme. Binding studies using fluorescence measurements revealed that the substrate shikimate 3-phosphate and glyphosate were able to bind the purified Lys-23 to Arg mutant enzyme but not to the purified catalytically inactive Lys-23 to Ala mutant enzyme. The above results suggest that the cationic group at position 23 of the enzyme may play an important role in substrate binding. PMID- 2900245 TI - Proton/product time course ratios: a new approach to transient-state kinetic analysis. AB - The usefulness of the indicator dye method for the detection of transient enzyme product intermediates has been very limited due to the near impossibility of resolving the apparent single exponential time courses resulting from sequences of steps linked by rather similar rate constants. We propose here a novel approach, the proton-product time course method, a procedure which can extract a great deal of the mechanistic information which remains buried in conventional proton release-time course measurements. The method involves nothing more than measuring the ratio, r, of the moles of H+ released to the moles of product formed as a function of time. We derive the theory relating this r function to mechanisms of varying complexity, explore the theoretical behavior of the function in various possible mechanistic situations, and employ the new approach in an experimental system. We demonstrate the fact that the proton/product time course ratio method can provide evidence of the existence of hidden steps in transient state kinetic studies, that it can determine accurate thermodynamic pK values of the intermediate complexes involved in those steps, and that it can produce time courses of individual intermediates which are obscure to conventional kinetic methods. PMID- 2900246 TI - Remodeling of a rat hepatocyte plasma membrane glycoprotein. De- and reglycosylation of dipeptidyl peptidase IV. AB - The present paper demonstrates the terminal de- and reglycosylation of a rat hepatocyte plasma membrane glycoprotein, dipeptidyl peptidase IV (DPP IV). Cultured hepatocytes were used in pulse-chase experiments with [3H]L-fucose and [14C]N-acetyl-D-mannosamine as markers for terminal carbohydrates, [3H]D-mannose as marker of a core-sugar, and [35S]L-methionine for labeling the protein backbone. Membrane DPP IV was immunoprecipitated with a polyclonal antibody which bound selectively at 4 degrees C to the cell-surface glycoprotein. The times of maximal labeling of hepatocyte plasma membrane DPP IV were 6-9 min for [3H]L fucose, 20 min for [3H]D-mannose, and 25 min for [35S]L-methionine. When antibodies were bound to cell-surface DPP IV at 4 degrees C, the immune complex remained stable for more than 1 h after rewarming to 37 degrees C, despite ongoing metabolic and membrane transport processes. This was shown by pulse labeling with [35S]L-methionine at 37 degrees C, followed by cooling to 4 degrees C, and addition of antibody against plasma membrane DPP IV. During rewarming, the radioactivity in the complex remained constant. In a similar experiment with [3H]L-fucose, the radioactivity in the immune complex declined rapidly, indicating a defucosylation of the plasma membrane glycoprotein. Using the same experimental design with [3H]D-mannose, the radioactivity in the immune complex remained constant, showing that the core-sugar D-mannose is not cleaved from the membrane glycoprotein. Terminal reglycosylation (refucosylation and resialylation) was demonstrated as follows. Hepatocytes were maintained at 37 degrees C in a medium supplemented with tunicamycin in order to block the de novo synthesis of N-glycosidically bound carbohydrate chains. At 4 degrees C the antibody against DPP IV bound only to cell surface glycoprotein. During the rewarming period at 37 degrees C, radioactivity from [3H]L-fucose and [14C]N acetyl-D-mannosamine became incorporated into the immune complex. This indicates a fucosylation and sialylation of the glycoprotein originally present at the cell surface. The mechanisms whereby terminal de- and reglycosylation of plasma membrane glycoproteins may occur during membrane recycling are discussed. PMID- 2900247 TI - Novel streptococcal mutants defective in the regulation of H+-ATPase biosynthesis and in F0 complex. AB - In Streptococcus faecalis (faecium), the cytoplasmic pH is regulated by proton extrusion via a proton translocating F1F0-ATPase; the level of this enzyme increases in response to cytoplasmic acidification (Kobayashi, H., Suzuki, T., and Unemoto, T. (1986) J. Biol. Chem. 261, 627-630). We describe here two novel acid-sensitive mutants, designated AS8 and AS17, that contain ATPase activity but fail to grow on acid media. Our data suggested that in mutant AS17, acidification of the cytoplasm stimulates synthesis of the F0 sector of the ATPase but not the F1 sector. The accumulation in the plasma membrane of F0 sectors devoid of F1 results in enhanced proton permeability, and as a consequence mutant AS17 is unable to regulate the cytoplasmic pH in acid media. The genetic defect may reside in a gene that regulates expression of the F1F0-ATPase. Mutant AS8 does not generate a proton motive force. Our results suggest that the F1F0-ATPase can hydrolyze ATP but fails to translocate protons due to a defect in one of the subunits of the F0 sector. PMID- 2900248 TI - Comparative susceptibility of a peptidoglycan monomer from Brevibacterium divaricatum and its anhydromuramyl analogue to hydrolysis with N-acetylmuramyl-L alanine amidase. Isolation and characterization of anhydromuramyl-peptidoglycan monomer. AB - Peptidoglycan monomer, GlcNAc-beta-(1----4)-MurNAc-L-Ala-D-iGln[ (L)-meso-A2pm (D)-amide-(L)-D-Ala-D-Ala] (PGM), from Brevibacterium divaricatum is composed of the disaccharide pentapeptide containing muramic acid with a reducing end (ca. 90 95%) and of the anhydromuramyl analogue (anhydromuranyl-PGM; ca. 5-10%), according to analysis by high-performance liquid chromatography (HPLC) and fast atom bombardment mass spectrometry (FAB-MS). The two peptidoglycan analogues cannot be separated by simple physico-chemical procedures. The enzyme N acetylmuramyl-L-alanine amidase (mucopeptide amidohydrolase, E.C. 3.5.1.28) cleaves the bond between N-acetylmuramic acid and L-alanine in the PGM molecule. It is shown that anhydromuramyl-PGM is also a substrate for the amidase. In a preparation containing both analogues, the amidase hydrolyses preferentially PGM rather than anhydromuramyl-PGM. The experimental conditions for treatment with the amidase were adjusted with respect to time and enzyme concentration to allow hydrolysis to proceed for several hours. The course of hydrolysis was followed by analysis of the unhydrolyzed substrate by HPLC, and FAB-MS at predetermined time intervals; after 6 h, the amount of anhydromuramyl-PGM in the unhydrolyzed substrate increased to 25% as compared to the starting material containing only 6%. Such a mixture was suitable for separation of components by preparative thin layer chromatography and for isolation of completely purified PGM and the corresponding anhydromuramyl analogue containing an intramolecular 1,6 anhydromuramyl end. The separated purified compounds were characterized by HPLC and their structure confirmed by FAB-MS-MS. PMID- 2900249 TI - Entamoeba histolytica antigens as possible vaccinogens? A short review. AB - A few key papers which have recently been published on the characterization of amoeba antigens are reviewed. Immunofluorescence tests and immunoelectron microscopy have demonstrated the localization of certain surface antigens on axenically cultured trophozoites. Most of the surface antigens have largely been shown to elicit a humoral response. The elicitation of cellular response has not been well illustrated. The localization of a large number of antigens in cytoplasmic vacuoles and plasma membrane indicates that a greater stimulus to the host would be provided by intracellular antigens than by those located on the surface of amoeba trophozoites. In a few inoculation studies, amoeba antigens, in combination with several adjuvants, have been successfully employed for inducing protective immunity in various animal model systems. These and other results clearly demonstrate that amoeba antigens are fully capable of generating humoral and as well as CMI responses. A combination of these two effector limbs of immunity can be fully exploited through effective use of future vaccines. PMID- 2900250 TI - Determination of clenbuterol and mabuterol in equine plasma by ion-pair liquid chromatography with electrochemical detection. Chromatographic and electrochemical characteristics. AB - A method for the routine determination of the beta-adrenergic drugs clenbuterol and mabuterol in equine plasma has been developed. The drugs were isolated from alkalinized plasma by liquid-liquid extraction. The organic phase was evaporated to dryness and the residue was dissolved in the mobile phase prior to injection. The recoveries were 98% and 95% for clenbuterol and mabuterol, respectively. The drugs were separated by reversed-phase high-performance liquid chromatography and quantitated by a use of a coulometric detector set at +0.75 V vs. the internal reference electrode. The influence of pH and amounts of organic modifier and ion pairing agent on the retention times was investigated. The relationship between peak current and concentration was linear up to 1 microgram/ml for both compounds. The limits of detection were 0.5 ng/ml for clenbuterol and 2 ng/ml for mabuterol with a signal-to-noise ratio of 3. A brief discussion of the electrochemistry of the compounds is given. PMID- 2900251 TI - [Growth hormone (GH) secretion during a 6-hour continuous infusion of GH releasing factor (GRF) in monosodium glutamate (MSG) administered rats]. PMID- 2900254 TI - Porous hydroxyapatite as a bone graft substitute in maxillary augmentation. An histometric study. AB - A porous HA matrix, which is available for clinical use, was compared with split rib autografts after maxillary contour augmentation in 17 dogs. Specimens were retrieved at 3, 6, 12, 24 and 48 months and undecalcified sections were prepared for microscopy and histometry. The implant and graft cross sectional areas did not change with time, although mechanical trauma caused early changes in implant area in some specimens. In all implants, union with the maxillary cortex occurred along with substantial bone ingrowth. An area under the periosteum contained soft tissue ingrowth. In all grafts, except one, union also occurred. However, bone ingrowth into the cancellous spaces was not apparent, or minimal. The implant specimens were composed of 34.7% HA matrix, 23.9% bone and 41.3% soft tissue. The bone ingrowth remained permanent for the study duration. A 6.5% decrease in HA matrix occurred between the 24 and 48 month time intervals, suggesting the presence of microporous surface resorption. The graft specimens were composed of 55.8% bone and 44.2% non-mineralized tissue, without change over time. The similarity in mineralized tissue composition of the implants (58.6%) and grafts (55.8%) supported the thesis that a porous HA matrix can function as a bone graft substitute. PMID- 2900253 TI - Restriction fragment length polymorphism studies show consistent loss of chromosome 3p alleles in small cell lung cancer patients' tumors. AB - Previous karyotypic analysis of human small cell lung cancer cell lines has demonstrated a consistent deletion of a portion of the short arm of chromosome 3(p14-23). DNA prepared from tumors and normal tissues obtained from 24 small cell lung cancer and two extrapulmonary small cell cancer patients was hybridized to four probes that detect restriction fragment length polymorphisms within chromosome region 3p14-21. Of the 25 patients who were heterozygous for at least one marker in this region in the DNA from normal tissue, 23 (92%) showed an unequivocal loss of heterozygosity in the DNA from their tumor tissue. From these studies we conclude that loss of alleles from the short arm of chromosome 3 is a consistent finding in unselected small cell lung cancer patients' tumor DNA. PMID- 2900255 TI - Endocrine-skin interactions. Cutaneous manifestations of adrenal disease, pheochromocytomas, carcinoid syndrome, sex hormone excess and deficiency, polyglandular autoimmune syndromes, multiple endocrine neoplasia syndromes, and other miscellaneous disorders. AB - Endocrinologic disorders occasionally manifest themselves by their associated and/or induced cutaneous abnormalities. In some instances, the initial and most prominent complaints of the patient are related to alterations in the skin, and therefore the dermatologist will at times be the first physician consulted. In this review we describe the cutaneous lesions that occur in patients with Cushing's syndrome, adrenal insufficiency, pheochromocytomas, carcinoid syndrome, sex hormone excess or deficiency, polyglandular autoimmune syndromes, and multiple neoplasia syndromes. Additionally, we discuss the relationship of acanthosis nigricans and xanthomas to endocrinologic disorders and the skin lesions that occur in association with the spotty pigmentation, myxoma, endocrine overactivity syndrome, and the polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome. PMID- 2900252 TI - Direct muscarinic cholinergic inhibition of hepatic glucose production in humans. AB - To explore the potential role of the parasympathetic nervous system in human glucoregulatory physiology, responses to the muscarinic cholinergic agonist bethanechol (5.0 mg s.c.) and antagonist atropine (1.0 mg i.v.) were measured in normal humans. There were no changes in the plasma glucose concentration or rates of glucose production or utilization following atropine administration. After bethanechol administration there were no changes in the plasma glucose concentration or fluxes despite increments in plasma glucagon (75 +/- 7 to 103 +/ 10 pg/ml, P less than 0.02). There were no changes in insulin or C-peptide levels. To test the hypothesis that direct muscarinic inhibition of glucose production was offset by an indirect action of the agonist, specifically increased glucagon secretion with consequent stimulation of glucose production, bethanechol was administered while glucagon levels were held constant with the islet clamp technique (somatostatin infusion with insulin, glucagon and growth hormone replacement at fixed rates). Under that condition the muscarinic agonist induced a 25% decrement in the plasma glucose concentration (101 +/- 8 to 75 +/- 8 mg/dl, P less than 0.05). When compared with separate clamp control studies (with placebo rather than bethanechol injection) both the rate of glucose production and the glucose concentration were reduced (P less than 0.05) following bethanechol injection; the rate of glucose utilization was unaltered. Thus, we conclude: Withdrawal of parasympathetic tone does not appear to be an important glucoregulatory process in humans. Direct muscarinic cholinergic inhibition of hepatic glucose production occurs in humans but during generalized muscarinic activation this is offset by an indirect muscarinic action, increased glucagon secretion with consequent stimulation of glucose production. Thus, particularly if regional neuronal firing occurs, the parasympathetic nervous system may play an important role in human glucoregulatory physiology. PMID- 2900256 TI - Efficacy and safety of loratadine (10 mg once daily) in the management of idiopathic chronic urticaria. PMID- 2900257 TI - Chronic treatment with beta adrenergic agonists and antagonists alters the composition of proteins in rat parotid saliva. AB - This investigation was undertaken to determine the role of beta-adrenergic receptors in the regulation of the protein composition of rat parotid saliva. Chronic treatment of rats with dobutamine, a beta 1-adrenergic agonist, resulted in changes in parotid saliva volume, protein concentration, and composition which were essentially the same as those changes which occurred following chronic treatment with isoproterenol, a non-specific beta-adrenergic agonist. Chronic treatment with the beta 2-adrenergic agonist, terbutaline, had no effect on parotid saliva volume, protein concentration, or composition. Chronic treatment of rats with a beta 1-adrenergic antagonist, metoprolol, had different effects on saliva dependent on the manner by which the drug was delivered. Twice-daily injections of metoprolol led to a decrease in flow rate, but protein concentration and composition were unaltered. When metoprolol was delivered by surgically implanted osmotic minipumps, neither the flow of parotid saliva nor its concentration of protein was altered; however, there was a reduction in the proportion of proline-rich proteins in saliva. Comparable changes in parotid saliva protein composition occurred when the minipumps delivered propranolol, a non-specific beta-adrenergic antagonist. Chronic treatment of rats with an alpha 2-adrenergic agonist (clonidine) or antagonist (yohimbine) was without effect on parotid saliva flow rate, protein concentration, or composition. These findings suggest that the synthesis of proline-rich proteins is regulated, in part, by beta-adrenergic receptor stimulation, and primarily by the beta 1-receptor subtype. PMID- 2900258 TI - Nonselective beta-receptor blocker effect on high density lipoprotein cholesterol after chronic exercise. AB - High density lipoprotein (HDL) cholesterol changes were followed in 45 men with coronary heart disease who underwent 12 weeks of monitored aerobic exercise. Twenty-five patients who were taking a nonselective beta-receptor blocking drug (Group 1) did not demonstrate a significant change in HDL cholesterol after exercise (mean difference 2.8 +/- 11.5 mg/dl), whereas patients who had not received a beta-blocking drug for greater than or equal to 3 months (Group 2) showed a significant increase (mean difference 8.4 +/- 5.5 mg/dl; p less than 0.05). However, for those patients in each group who had an initial HDL cholesterol level less than 35 mg/dl before exercise, there was a significant increase in HDL cholesterol levels (mean difference 8 +/- 6.9 mg/dl [p less than 0.02] and 11 +/- 3 mg/dl [p less than 0.001] for Group 1 and Group 2, respectively) and a significant decrease in the low density lipoprotein (LDL/HDL cholesterol ratio (mean difference -1.2 +/- 1.6 [p less than 0.05] and -0.9 +/- 0.57 [p less than 0.001], respectively). Patients in both groups who started exercise with an HDL cholesterol level greater than 35 mg/dl did not show a significant change after exercise. Patients in Groups 1 and 2 achieved similar levels of exercise training after 12 weeks and were closely matched in age, medications, alcohol intake and smoking. The results indicate that among high risk patients (with an abnormally low HDL cholesterol level) exercise training can induce an augmentation of HDL cholesterol in those receiving a beta-blocking drug similar to that of patients not receiving such a drug. PMID- 2900259 TI - Use of an ultrashort-acting beta-receptor blocker (esmolol) in patients with acute myocardial ischemia and relative contraindications to beta-blockade therapy. AB - The hemodynamic responses to esmolol, an ultrashort-acting (t1/2 = 9 min) beta 1 adrenergic receptor antagonist, were examined in 16 patients with myocardial ischemia and compromised left ventricular function as evidenced by a mean pulmonary capillary wedge pressure of 15 to 25 mm Hg. Esmolol was infused intravenously to a maximal dose of 300 micrograms/kg body weight per min for less than or equal to 48 h in 16 patients: 9 with acute myocardial infarction, 6 with periinfarction angina and 1 with acute unstable angina. The sinus rate and systolic arterial pressure declined rapidly in all patients from baseline values of 99 +/- 12 beats/min and 126 +/- 19 mm Hg to 80 +/- 14 beats/min (p less than 0.05) and 107 +/- 20 mm Hg (p less than or equal to 0.05) during esmolol treatment. Rate-pressure product decreased by 33% and cardiac index by 14% during esmolol treatment, but pulmonary capillary wedge pressure was not significantly altered by drug infusion (19 +/- 3 mm Hg at baseline versus 19 +/- 5 during treatment, p = NS). In all patients there was a rapid return toward baseline hemodynamic measurements within 15 min of stopping administration of esmolol, and virtually complete resolution of drug effect was evident within approximately 30 min. During infusion of esmolol, four of nine patients receiving intravenous nitroglycerin required downward adjustment of nitroglycerin infusion rate to maintain systolic blood pressure greater than 90 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900260 TI - Beta adrenergic blocking agents for open-angle glaucoma. AB - Beta adrenergic blocking agents have gained wide acceptance among practitioners and patients alike as extremely useful drugs for the treatment of open-angle glaucoma. This new class of antiglaucoma agents usually is effective in reducing elevated intraocular pressure and is generally well tolerated. This paper is intended to provide an understanding of the ophthalmic beta adrenergic blocking agents to optometrists who are actively involved in the treatment of glaucoma and/or in the monitoring of glaucoma patients. The clinical pharmacology of the three FDA-approved beta blockers -- timolol, levobunolol, and betaxolol, is evaluated and the drugs are compared. PMID- 2900262 TI - The significance of impaired performance. PMID- 2900261 TI - Complications following traumatic incidents with STA-peg procedures. AB - The authors describe use of a Silastic plug to limit subtalar joint motion in symptomatic pediatric flatfeet. Three patients sustained postoperative injury resulting in pedal complications. Successful resolution of these cases is discussed. PMID- 2900264 TI - Immunocytochemical localization of aromatic L-amino acid decarboxylase in human, rat, and mouse bronchopulmonary and gastrointestinal endocrine cells. AB - Aromatic L-amino acid decarboxylase (AADC) catalyzes the cellular decarboxylation of L-aromatic amino acids and is therefore involved in the synthesis of several biogenic amines. Application of the indirect immunoperoxidase method on human, rat, and mouse tissues using specific antibodies to AADC revealed all AADC containing cells. Besides mast cells and adrenergic nerve fibers, the following cells were immunostained: neuroendocrine cells in the tracheobronchial epithelium; neuroepithelial bodies in the bronchopulmonary epithelium; Kultschitzky cells in the small intestine and appendix as well as adrenal chromaffin cells. All the latter cells belong to the so-called APUD system, the "D" in the acronym standing for the activity of the enzyme aromatic L-amino acid decarboxylase. Immunocytochemistry for AADC may become an additional tool not only to highlight APUD cells in tissue sections but also to differentiate the sites of cellular amine synthesis from those of amine storage. PMID- 2900263 TI - Detection of receptors for sulfated polysaccharides in human placenta by biotinylated probes. AB - Histochemical detection of binding sites for sulfated polysaccharides believed to be important mediators within recognitive interactions was carried out by application of biotinylated probes such as heparin, native and desulfated fucoidan, dermatan sulfate, and two types of carrageenans. The probes were derivatized by mild cyanogen bromide activation and subsequent aminoalkylation to allow incorporation of biotin, inserted with an epsilon-aminocaproic acid spacer to reduce charge-related and steric impediments. Specific labeling could be detected in different cell types of human placenta, dependent on the developmental stage. Sulfated polysaccharides bound predominantly to leucocytes in full-term placenta, whereas demonstration of specific binding sites in decidua, syncytiotrophoblasts, and cytotrophoblasts was restricted primarily to heparin and, less intensely, fucoidan, although not desulfated fucoidan. Heparin binding in the placenta after 8 weeks of gestation was reduced for epithelia that, at this stage of development, revealed carrageenan binding sites. Fucoidan binding was at this developmental stage measurable only for leucocytes. These results provide definite histochemical evidence for the presence and developmental regulation of expression of receptors for sulfated polysaccharides in different cell types of human placenta. PMID- 2900265 TI - Sandwich enzyme immunoassay of tumor-associated antigen sialosylated Lewisx using beta-D-galactosidase coupled to a monoclonal antibody of IgM isotype. AB - Enzyme conjugates with antibody of IgG type have been used extensively in immunohistochemistry, but conjugates with antibody of IgM type have not been reported. This paper describes the beta-D-galactosidase (Gal) labeling of a monoclonal IgM antibody designated CSLEX1 (for cytotoxic sialosylated Lewisx), which is directed against a tumor-associated antigen sialosylated Lewisx (S-Lex). The antibody was first acylated with a heterobifunctional agent N-(gamma maleimidobutyryloxy)succinimide (GMBS) to introduce the maleimide groups into the molecule; excess reagent was removed by gel filtration and then the activated antibodies were crosslinked to the thiol groups of Gal. The conjugates were partially purified of free Gal by DEAE-Toyopearl column chromatography with an increasing linear concentration of NaCl. The conjugates thus prepared retained almost full enzyme activity and were demonstrated to be free of CSLEX1 by affinity chromatography using anti-galactosidase antibody bound to Sepharose 4B. The conjugates were used as a label in a sandwich enzyme immunoassay (SEIA) to detect the antigen at concentrations as low as 0.2 U/well. The SEIA was used to measure serum S-Lex levels in both healthy subjects and lung cancer patients and mean concentrations of 70 U/ml and 198.6 U/ml were detected respectively. PMID- 2900266 TI - Binding and internalization of rat colonic mucins by the galactose/N-acetyl-D galactosamine adherence lectin of Entamoeba histolytica. AB - Purified rat colonic mucins inhibit Entamoeba histolytica in vitro adherence to and lysis of colonic epithelial cells by binding to the amoebic galactose/N acetyl-D-galactosamine (Gal/GalNAc)-inhibitable adherence lectin. We found that 125I-labeled mucins demonstrated saturable Gal-specific binding to E. histolytica trophozoites (strain HM1:IMSS), with 2.8 x 10(3) binding sites per amoeba and a dissociation constant of 8.20 x 10(-11) M-1. Inhibition of parasite protein synthesis completely abrogated mucin binding; elevation of amoebic vesicle pH with ammonium chloride (10 mM) had no effect. Surface-bound 125I-labeled mucins were rapidly internalized and released from amoebae without evidence of proteolytic degradation. Three avirulent HM1 clones contained immunoreactive Gal/GalNAc lectin molecules with high-affinity binding of 125I-labeled mucins but exhibited markedly reduced rates of uptake and exocytosis of bound mucins. High affinity binding by the Gal/GalNAc adherence lectin was followed by rapid internalization and eventual release of the colonic mucins. Additionally, defects in lectin surface expression and endocytosis were found in the avirulent clones. PMID- 2900267 TI - Asymptomatic bacteriuria in elderly women. PMID- 2900268 TI - Expression of P fimbriae in urine. PMID- 2900269 TI - [IgM anti-ATLA antibodies in HTLV-I healthy carriers and patients with adult T cell leukemia and HTLV-I associated myelopathy]. PMID- 2900270 TI - [Combined treatment of plasmapheresis and methylprednisolone pulse therapy to polyarteritis nodosa with rapidly progressive glomerulonephritis]. PMID- 2900271 TI - [Evaluation of lymphocyte-subset of the cerebrospinal fluid and the peripheral blood in a case with adult T-cell leukemia meningitis]. PMID- 2900272 TI - The repairability of oxidative free radical mediated damage to DNA: a review. AB - Many DNA repair enzyme activities are present in both prokaryotic and eukaryotic organisms. Among these are DNA exo- and endonucleases and DNA glycosylases which remove oxidatively damaged portions of the DNA molecule, thereby initiating excision-repair. The existence of these enzymes may be taken as evidence that cellular DNA is continuously subject to endogenous oxidative stress. Many of the lesions introduced by ionizing and ultraviolet radiation are identical to those introduced into DNA by reactive oxygen species generated by activated white cells, and are substrates for the repair enzymes. The chemical nature of the lesions, their biologic effects, and the mechanism of their repairability are described. PMID- 2900273 TI - Radiation doses in Sweden resulting from the Chernobyl fallout: a review. AB - The risk associated with the Chernobyl fallout is the product of radiation dose and risk factor per dose unit. The radiation doses originate from inhalation of radioactive particles, ground irradiation from deposited nuclides and internal irradiation caused by contaminated food. In Sweden the largest dose contribution is due to external radiation. The deposition has been mapped by aerial measurements and in situ high-resolution gamma measurements at ground level over the whole country. On the basis of these measurements, population-weighted doses for external radiation have been estimated. Whole-body measurements on randomly selected individuals have been performed in order to estimate the average dose from internal irradiation. The collective dose, i.e. the sum of all individual doses, has been estimated to be about 1500 man-Sievert for the first year after Chernobyl and 5000-7000 man-Sievert for a 50-year period. Using a risk factor of 0.02 fatal cancers per man-Sievert the Chernobyl fallout over Sweden might cause 100-200 fatal cancers. PMID- 2900274 TI - 131I dose to the human fetal thyroid in the Zagreb district, Yugoslavia, from the Chernobyl accident. AB - The 131I activity was measured in 30 human fetal thyroids in Zagreb district after the Chernobyl accident. A model of radioiodine metabolism in the mother and human fetus which takes into account the age dependence of the uptake and retention of radioiodine in the fetal thyroid was developed. Having assessed that the total intake by the average mother was about 1330 Bq, a good correlation between calculated and measured fetal thyroid activities was found (r = 0.77, P less than 0.001). The fetal thyroid dose reached the maximum of 0.43 micro Gy/Bq intake at about the fifth month of gestation. It was concluded that the risk of having a child with a harmful trait due to 131I absorbed by the mother was negligible. PMID- 2900275 TI - Superoxide radical reactions in aqueous solutions of pyrogallol and n-propyl gallate: the involvement of phenoxyl radicals. A pulse radiolysis study. AB - The reactions of O2-. in aqueous solutions of pyrogallol 1 and the antioxidant n propyl gallate 2 have been studied. In both cases the initial reaction gives hydrogen peroxide and the corresponding phenoxyl radical (k(1 + O2-.) = 3.4 x 10(5), k(2 + O2-.) = 2.6 x 10(5) dm3 mol-1S-1). These phenoxyl radicals have been produced independently by reacting 1 and 2 with Br2-. and their spectra and first pKa values measured (pKa(phenoxyl radical from 1) = 5.1, pKa(phenoxyl radical from 2) = 4.1). It is necessary to correct the observed spectra for the contribution of the H-adducts, formed by the reaction of radiolytically produced H atoms with the substrates (k(1 + H) = 2.5 x 10(9), k(2 + H) = 3.8 x 10(9) dm3 mol-1 S-1). The H-adduct spectra are given. In the reactions of O2-. with the substrates the initial transient absorbances are characteristic of the phenoxyl radicals; however at longer times a new transient absorbing around 500 nm (epsilon congruent to 10(4) dm3 mol-1 cm-1) appears. This is believed to be the deprotonated hydroxy-orthoquinone, formed by the reaction of phenoxyl radicals with O2-. (k congruent to 1.5 x 10(8) dm3 mol-1 S-1, from kinetic curve-fitting). The absorbance due to the hydroxy-orthoquinones decays by first-order kinetics (1.6 x 10(2) in the case of 1 and 1.1 x 10(2) s-1 in the case of 2). This is thought to be mainly the result of the conversion of the hydroxy-orthoquinone into its hydrate. Similar experiments were carried out with catechol and ethyl protocatechuate. The chemistry appears to be similar to that of the pyrogallol derivatives. The rate constant for reaction of these compounds with O2-. is, however, only less than or equal to x 10(4) dm3 mol-1 s-1. PMID- 2900276 TI - Effect of DNA conformation on the hydroxyl radical-induced formation of 8,5' cyclopurine 2'-deoxyribonucleoside residues in DNA. AB - Reactions of hydroxyl radicals with DNA form a variety of base and sugar products and 8,5'-cyclopurine 2'-deoxyribonucleoside residues in DNA. Here we report the effect of DNA conformation on the yields of 8,5'-cyclopurine 2'-deoxynucleosides and the ratios of their (5'R)- and (5'S)-diastereomers. Calf thymus DNA in native (double-stranded DNA) or heat-denatured form (single-stranded DNA) was exposed to hydroxyl radicals generated by ionizing radiation in nitrous oxide-saturated phosphate buffer. Doses ranging from 10 to 40 Gy were used to ensure low levels of damage to DNA and thus to preserve its secondary structure in experiments with double-stranded DNA (ds-DNA). After irradiation, DNA was hydrolysed enzymatically to 2'-deoxyribonucleosides. The hydrolysates were dried, trimethylsilylated, and analyzed by capillary gas chromatography-mass spectrometry with selected-ion monitoring. An internal standard was used for quantitative measurements and added to DNA samples prior to enzymatic hydrolysis. The yields of 8,5'-cyclo-2' deoxyadenosine and 8,5'-cyclo-2'-deoxyguanosine in single-stranded DNA (ss-DNA) were higher than those in ds-DNA. The (5'R)-diastereomers of both compounds were found to predominate over their (5'S)-diastereomers in ss-DNA. In contrast, the yields of the (5'S)-diastereomers in ds-DNA were slightly higher than those of the (5'R)-diastereomers. The G values of 8,5'-cyclo-2'-deoxyadenosine in ss-DNA and ds-DNA were 0.042 and 0.025, respectively. Those of 8,5'-cyclo-2' deoxyguanosine in ss-DNA and ds-DNA were 0.038 and 0.017, respectively. PMID- 2900277 TI - Induction of double-strand breaks following neutron capture by DNA-bound 157Gd. AB - Irradiation of plasmid DNA/Gd3+ mixtures with thermal neutrons induces DNA double strand breaks (dsb). However, the extent of breakage is markedly reduced by sequestering the Gd3+ from DNA by addition of EDTA. Since the 157Gd neutron capture event involves some internal conversion, we suggest that the DNA dsb induction results from Auger electron emission. PMID- 2900278 TI - DNA strand breaks induced by gamma irradiation and alkaline treatment: a computer program for the analysis of the influence of the sequence. AB - Deoxyoligonucleotides 32P-labelled at one end have been used to probe the DNA chain breakage induced by external gamma-irradiation and alkali treatment. The fragments were separated according to their chain lengths by polyacrylamide gel electrophoresis and their radioactivity counted. Quantitative analysis of the distribution pattern of the intensity fragments was performed by computer. In this article the principles of the calculation program are given. The basic units corresponding to adenine, thymine, cytosine and guanine exhibited different radiosensitivities. It was possible to estimate the mean chain rupture per nucleotide and per Gray for G, T, C and A. These coefficients were derived from experimental values by iteration. Thus, it is possible to simulate very accurately the oligonucleotide fragment intensities. The relative error was usually less than 10 per cent for most of the nucleotide units. In this way small differences in the band intensities may be demonstrated. They can be explained by variations of the local conformation of the biopolymer. PMID- 2900279 TI - Repair of potentially mutagenic damage, sensitive to anisotonic treatment, in actively growing Chinese hamster cells. AB - Using exponentially growing Chinese hamster V79 cells we studied the effect of anisotonic phosphate-buffered saline (PBS) treatment on the frequency of mutation following X-irradiation. Induction of mutants was studied at the hypoxanthine guanine phosphoribosyl transferase locus (HGPRT). When cells were X-irradiated and immediately followed by 0.5 M NaCl/PBS treatment for 20 min at 37 degrees C, cell survival was significantly decreased and a concomitant increase in the number of mutants was observed, indicating that postirradiation treatment with anisotonic salt solution caused conversions of potentially lethal damage and potentially mutagenic damage to lethal and mutagenic damage, respectively. The repair kinetics of potentially mutagenic damage expressible by 0.5 M NaCl/PBS after 5.86 Gy of X-rays were similar to those of potentially lethal damage. The repair of both types of damage was essentially complete within 40 min after X irradiation. PMID- 2900280 TI - Modification of radiation dose-rate sparing effects in a human carcinoma of the cervix cell line by inhibitors of DNA repair. AB - The in vitro cell survival of a human cervix carcinoma cell line (HX156c) has been assessed using 60Co gamma-rays administered at either high (150 cGy/min) or low (3.2 cGy/min) dose rate. Recovery during low dose-rate irradiation was observed; the dose reduction factor at 10(-2) cell kill for 150 versus 3.2 cGy/min was around 1.3. An insight into the possible underlying mechanisms of this recovery process has been investigated by addition of non-toxic concentrations of various agents thought to inhibit eukaryotic DNA repair. Agent were added 2 h prior to irradiation and removed after 24 h exposure. Differential effects among the inhibitors were observed; aphidicolin had no effect on cell survival, novobiocin, hydroxyurea and 3-aminobenzamide reduced survival by a similar extent at both dose rates, beta-ara A and caffeine reduced survival to a greater extent during low dose-rate irradiation. beta-ara A and caffeine seemed to exert their effects mainly by increasing the alpha component of the acute survival curve. Since survival curves obtained at dose rates of around 3 cGy/min help define a dominant component of the initial slope of the acute curve we have demonstrated that beta-ara A and caffeine modify the initial slope, probably by inhibiting DNA repair processes involved in the sparing of tumour cells during protracted irradiation. PMID- 2900281 TI - Regulation of DNA repair kinetics in proliferative and quiescent tumor cells. AB - The radiosensitivity and kinetics of repair of radiation-induced DNA damage were determined for proliferative (P) and quiescent (Q) cells of the mouse mammary adenocarcinoma line 67. 67 Q cells are more radiosensitive than 67 P cells. Radiation induced the same amount of DNA damage in both 67 P and 67 Q cells. Both 67 P and 67 Q cells repaired their DNA damage with biphasic kinetics, but the half-times for the fast and slow phase were longer in 67 Q cells. Q cell DNA appeared to be in a more compact or condensed chromatin structure and was less accessible to enzymatic digestion than P cell DNA. These data suggest that 67 Q cells are more sensitive to ionizing radiation than 67 P cells because they repair their radiation-induced DNA damage more slowly, perhaps as a result of their more condensed chromatin structure. PMID- 2900282 TI - G2 arrest in mouse zygotes after X-irradiation: reversion by caffeine and influence of chromosome abnormalities. AB - The effect of caffeine was studied on mouse zygotes blocked in the G2 phase of the first cell cycle after X-irradiation. Caffeine (2 mM) effectively reversed the G2 arrest when zygotes were incubated in its presence at the time when first mitosis normally takes place. This effect of caffeine was inhibited by cycloheximide (5 micrograms ml-1). In embryos escaping the G2 arrest the frequencies of chromosome aberrations varied as a function of the time of irradiation, showing a clear relationship with the varying rates of lethality occurring from the morula stage. Blocked zygotes suffered major chromosome damage: however, this did not appear to be the only cause of the G2 arrest. Triploid zygotes were preferentially blocked, suggesting that nuclei contain the target for this X-ray effect. Mouse zygotes are a useful model for studies on G2 arrest and normal cell division regulation. PMID- 2900283 TI - Radioprotection of cultured Chinese hamster ovary cells by WR-255591. AB - We examined the radioprotective effect of the aminothiol WR-255591 and its phosphorothioate derivative WR-3689 on aerated cultured Chinese hamster ovary cells. At concentrations up to 10 mmol dm-3, WR-3689 afforded little protection from the lethal effects of gamma-radiation. The free thiol WR-255591, on the other hand, efficiently protected these cells, giving a protection factor (PF) for cell survival of 2.3 at a concentration of 6 mmol dm-3. The effects of WR 255591 on the induction and rejoining of gamma-ray-induced DNA single-strand breaks (ssb) and double-strand breaks (dsb) were measured using alkaline (pH 12.1) and neutral (pH 7.0 or 9.6) elution, respectively. PFs calculated from these data were compared with the PFs measured for cell survival. WR-255591 (6 mmol dm-3) protected against the induction of both DNA ssb and dsb; however, the magnitude of the modification of both ssb (PF of 1.23) and dsb (PF of 1.83 at pH 7.0 and 1.70 at pH 9.6) was less than that for cell survival (PF of 2.3) measured under identical conditions (irradiation on ice). Treatment of cells with WR 255591 prior to irradiation retarded the subsequent rate of ssb rejoining but had no effect on dsb rejoining. Postirradiation treatment with the drug slightly retarded ssb rejoining but had no effect on cell survival. The observation of lower PFs for DNA strand breaks than for cell survival suggests that radioprotection by WR-255591 probably does not result from a uniform decrease in the induction of all types of DNA lesions. Rather, the drug may differentially protect against the induction of subclasses of DNA damage--which could also explain the effects on the kinetics of ssb rejoining--and/or enhance cellular recovery processes. PMID- 2900285 TI - Influence of heat treatment on osmotic fragility of carp erythrocytes. PMID- 2900284 TI - DNA damage does not appear to be a trigger for thermotolerance in mammalian cells. AB - The hypothesis that DNA damage is the trigger for thermotolerance in mammalian cells was tested in Chinese hamster ovary cells by looking for evidence of thermotolerance after ionizing radiation or ultraviolet light exposure. As previous studies have demonstrated that relatively non-toxic radiation exposures do not induce thermotolerance in mammalian cells (Li et al. 1976), higher doses, comparable to those used in yeast to induce thermotolerance (Mitchel and Morrison 1984), were tested in this study. Doses of this magnitude are lethal to mammalian cells, thereby precluding the use of clonogenic survival as an endpoint. We therefore used three alternative assays which are indicators of the subsequent development of thermotolerance. These were; (a) heat-induced inhibition of total protein synthesis, (b) heat-induced uptake of dansyl lysine, and (c) synthesis of heat shock proteins. Only total protein synthesis revealed evidence of a small degree of thermotolerance which occurred immediately after ionizing radiation exposure. By 4 h postirradiation the tolerance, as measured by this assay, was no longer evident. No evidence of thermotolerance was seen following UV exposure. In addition, when a large radiation dose was given either immediately before or after a heat treatment used to induce thermotolerance, there was no alteration in the level of heat-induced tolerance, despite the extensive number of DNA stand breaks caused by the radiation. Our data therefore suggest that, in mammalian cells, the type of DNA damage caused by ionizing radiation is not the trigger for the induction of thermotolerance. PMID- 2900286 TI - Evaluation of random cDNA clones as probes for human restriction fragment length polymorphisms. AB - We constructed two human cDNA libraries and selected clones hybridizing with more than five fragments of digested genomic DNA. We assume that these cDNAs detect sequences belonging to gene families. Compared with cDNAs derived from mRNAs of other tissues, the cDNAs of lymphocytes contained a higher proportion of these selected species of cDNA. We assume that these extra cDNAs are tissue-specific. In parallel tests, cDNAs belonging to gene families detected more restriction fragment length polymorphisms than did genomic probes, due to the larger number of restriction sites that can be checked using one probe. However, the chromosomal assignment of these polymorphisms often proved to be very difficult. In addition, we noticed that the mean length of EcoRI fragments hybridizing with our cDNAs is greater than the mean length of fragments hybridizing with randomly chosen genomic probes, possibly due to methylation connected with the inactivation of related active gene sequences. PMID- 2900287 TI - A multicentre study of the new Reflotron system for the measurement of urea, glucose, triacylglycerols, cholesterol, gamma-glutamyltransferase and haemoglobin. AB - Reflotron, a solid phase reagent technology capable of measuring a wide range of analytes on whole blood, plasma or serum samples has been evaluated with reference to urea, glucose, cholesterol, triacylglycerols, haemoglobin and gamma glutamyltransferase analyses. The results show good concordance with conventional wet chemistry methods, with comparable imprecision. Performance is not affected by variations in haematocrit up to 0.55 or bilirubin concentrations at least up to 250 mumol/l. PMID- 2900288 TI - Measurement of activation energy of gamma-glutamyltransferase as a marker for enzyme heterogeneity. AB - In order to detect differences between various multiple forms of gamma glutamyltransferase, the activation energy was measured. In the serum of patients with liver diseases, activation energy was measured. In the serum of patients with liver diseases, activation energy of the serum enzyme is higher than in normal individuals (41.9 +/- 1.2 vs. 38.9 +/- 1.5 kJ/mol, p less than 0.05). Neuraminidase treatment resulted in a reduction of activation energy. Various multiple forms of serum gamma-glutamyltransferase, as prepared by lectin affinity chromatography (concanavalin A, Ricinus communis I and II, wheat germ agglutinin) showed activation energy differences between binding and nonbinding fractions. Similar results were observed in seminal plasma gamma-glutamyltransferase, when patients with accessory gland infection were compared with a reference population. Our results suggest that the activation energy depends upon differences in the carbohydrate part of the enzyme. The low gamma glutamyltransferase activation energy of tissue extracts increased significantly after butanol extraction and was then comparable with serum activation energy values, which suggests that lipid-binding is a factor in activation energy variation. In most cases, gamma-glutamyltransferase activities measured at a certain temperature can be easily converted to a corresponding activity at another temperature, but in severe liver disease significant errors may be introduced when simple temperature conversion factors are used. PMID- 2900289 TI - Conservation of antigenic properties and sequences encoding the envelope proteins of prototype Hantaan virus and two virus isolates from Korean haemorrhagic fever patients. AB - Viruses isolated from the blood of two Korean haemorrhagic fever patients were propagated in cell culture and compared to prototype Hantaan virus which was isolated from Apodemus mice. The antigenic properties of the human isolates were found to be closely related to Hantaan virus by plaque reduction neutralization, haemagglutination inhibition and fluorescent antibody staining with both polyclonal and monoclonal antibodies. The medium genome segment of each human isolate was sequenced and compared to that of Hantaan virus. Nucleotides comprising the Hantaan virus G1 and G2 envelope protein-coding regions differed from those of the other viruses by only 5.4% and 5.7%. The human isolates differed from one another by 1.6%. The nucleotide differences resulted in predicted amino acid variations of 1.3% to 2.3% among the three viruses, with the majority occurring as conservative substitutions in G1. PMID- 2900290 TI - The aortic alpha 1-adrenergic receptor in familial amyloidotic polyneuropathy. AB - To assess the pathophysiology of the sympathetic nervous system in familial amyloidotic polyneuropathy (FAP), we used 3H-bunazosin to identify and characterize the alpha 1-adrenergic receptor in human aortic membranes. The binding of 3H-bunazosin was rapid, readily reversible, stereospecific, and saturable. The Scatchard analysis described a single class of binding sites with a dissociation constant (KD) of 0.370 +/- 0.035 nM and a maximal binding capacity (Bmax) of 11.8 +/- 1.30 fmol/mg protein in control patients. Competition analysis demonstrated the alpha 1-adrenergic specificity of the 3H-bunazosin binding sites in human aortic membranes. The KD and Bmax of 3H-bunazosin binding in four FAP patients was 0.274 +/- 0.052 nM and 7.79 +/- 0.15 fmol/mg protein, respectively; these values did not differ significantly from those in 14 control patients. An increase in Bmax or affinity of alpha 1-adrenergic receptors may not be the cause for denervation supersensitivity in FAP. PMID- 2900291 TI - Receptor changes during chronic dopaminergic stimulation. AB - The underlying cause of the long term complications of L-DOPA or dopamine agonist therapy in Parkinson's disease remains unknown. Previous studies of repeated administration of L-DOPA or bromocriptine to rodents have shown increases, decreases or no change in brain dopaminergic activity. For this reason we have re examined the effects of chronic L-DOPA or dopamine agonist administration on brain dopamine receptor function in rats. Repeated intraperitoneal administration of L-DOPA to rats for 21 days followed by 3 days drug withdrawal caused an enhancement of apomorphine-induced stereotypy but no apparent alteration in striatal dopamine receptor numbers or affinity (as judged by 3H-spiperone; 3H-NPA and 3H-piflutixol binding). Chronic oral administration of L-DOPA plus carbidopa to rats for one year was without effect on apomorphine-induced stereotypy or striatal D-2 dopamine receptors. Similarly, no effects were observed on striatal dopamine function following one year's administration of bromocriptine. Pergolide produced an enhancement of apomorphine-induced stereotypy but a decrease in D-2 receptor density as judged by 3H-spiperone binding. In rats with a unilateral 6 OHDA lesion of the medial forebrain bundle the oral administration of L-DOPA plus carbidopa for 4 weeks, followed by 4 days withdrawal, enhanced the rate of apomorphine-induced contraversive rotation. It appears difficult, at least in rats, to manipulate striatal dopamine receptors with L-DOPA or dopamine agonist drugs. An enhancement of motor behaviour can occur in the presence of no change or a decrease in dopamine receptor numbers identified by in vitro ligand binding to tissue homogenates. PMID- 2900292 TI - Somatostatin content and receptors in the cerebral cortex of depressed and control subjects. AB - Somatostatin-like immunoreactivity is reduced in the cerebrospinal fluid in depression and this is presumed to reflect alterations in cerebral somatostatinergic systems. We have examined this hypothesis by measuring this immunoreactivity and somatostatin receptors in post-mortem cortical tissue from depressed patients and control subjects. There was no significant difference in the temporal and occipital cortex in somatostatin-like immunoreactivity or in somatostatin receptor affinity and binding capacity between depressed and control groups. It is concluded that there may not be an alteration of cortical somatostatin function in depression. PMID- 2900293 TI - Neuroleptic-induced Parkinson's syndrome: clinical features and results of treatment with levodopa. AB - Twenty six consecutive patients with neuroleptic-induced Parkinson's syndrome (NIPS) are described. Their median age was 61 years, 60% were female, and most had received chronic neuroleptic medication for psychiatric indications. The clinical features were indistinguishable from idiopathic Parkinson's disease, except for the presence of co-existing orofacial chorea, limb dyskinesia or akathisia which provided an aetiological clue in 11 cases. Complete resolution of NIPS occurred in only two patients, one of whom later developed Parkinson's disease. Sixteen patients were treated with 300-1000 mg levodopa/benserazide for up to 4 years with few adverse effects but therapeutic response was disappointing. PMID- 2900294 TI - Involuntary orofacial movements in hospitalised patients with mental handicap or epilepsy: relationship to developmental/intellectual deficit and presence or absence of long-term exposure to neuroleptics. AB - Among 42 adult patients with mental handicap who had received treatment with neuroleptic drugs, the prevalence of orofacial dyskinesia increased with age and those with such involuntary movements were characterised by a considerably greater degree of mental handicap. Similar associations were found among a group of 15 patients with epilepsy. Two of seven other mentally handicapped patients and one of eight other epileptic patients showed indistinguishable orofacial dyskinesia, despite no record of them having received neuroleptic drugs. PMID- 2900295 TI - Contribution of GABAergic inhibition to the response characteristics of auditory units in the avian forebrain. AB - 1. We tested the contribution of GABAergic inhibition to the response characteristics of 213 neurons in the auditory telencephalon of chronically prepared nonanesthetized chickens. Extracellular recordings were obtained with multibarrel glass electrodes containing a tungsten wire. Auditory stimuli consisted of tones, two-tone combinations, and noise bursts presented either free field or via earphones. 2. Response properties of the neurons were studied both before and during iontophoretic application of GABA, glutamate, bicuculline methiodide (BIC), and acetylcholine. 3. During BIC application excitatory responses were facilitated. With the exception of transient off-responses, which occasionally appeared only in the BIC condition, the temporal response patterns to tone stimuli at the units' best frequency usually were unaltered. In no case was an inhibitory response component to binaurally presented pure tones antagonized by BIC. 4. BIC iontophoresis enlarged the isointensity-response areas of the vast majority of neurons in the structures of the auditory forebrain lying postsynaptic to the thalamorecipient layer L2. This effect was not obtained when neurons were depolarized to perithreshold levels with glutamate. 5. Two-tone stimulation resulted in a suppression of the excitatory response to a neuron's best frequency when the second frequency lay outside the excitatory response area. In lamina L2, the frequency range inducing two-tone suppression was narrow, and the suppressive effect was not antagonized by BIC. In the postsynaptic layers, frequencies up to three octaves from the neurons' best frequency induced two-tone suppression that was sensitive to BIC. In addition, these neurons also displayed a BIC-insensitive suppression similar to the one seen in layer L2. 6. Neurons displaying no or only a poor response to white-noise stimulation strongly responded to this wide-band stimulus during BIC iontophoresis. 7. Neurons without tone responses usually displayed clear response areas to tones during BIC application. Iontophoretic application of acetylcholine, but not glutamate, also induced such tone responses. Two-tone combinations with frequencies lying within the response areas observed in the BIC condition elicited excitatory responses after full recovery from the BIC application. 8. During BIC iontophoresis nonmonotonic intensity-response functions were converted to monotonic functions in most of the neurons studied. 9. A model of GABAergic inhibitory interactions is proposed that is based on two independent GABAergic systems.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2900297 TI - Importance of pulmonary blood volume and aortic blood pressure in regulation of left ventricular function. PMID- 2900298 TI - Rhythms in pineal immunoreactive somatostatin in the Syrian hamster, mouse, and gerbil. AB - Immunoreactive somatostatin (IRS) has been previously demonstrated in the pineal gland of different rodent species, and we observed a 24-hr rhythm in rats. Recent data suggest that the peptide may represent a neurotransmitter in the so-called peptidergic nerves of the central, pinealopetal innervation of the epiphysis, which may modulate the activity and secretion of the gland. We investigated whether 24-hr changes of pineal IRS content occurred in Syrian hamsters, gerbils, and mice. Adult males, kept in a 14:10 LD photoperiod, were decapitated at 4-hr intervals throughout a 24-hr period. Pineals and median eminences were analyzed for IRS by radioimmunoassay. No significant changes in the median eminence content of IRS with time was observed. As previously described in rats, a statistically significant rhythm of IRS was observed in the pineal of hamsters and mice, with a peak at 2000 hr (mice 51.7 +/- 5 pg/pineal; hamsters 26.3 +/- 4.6) and a nadir at 2400 hr (mice 30.8 +/- 1.4) or 0400 hr (hamsters 8.6 +/- 1). However, in the gerbil pineal IRS content remained unchanged throughout the period of study. Since the three species examined have very different melatonin cycles, it is suggested that the melatonin and IRS rhythms are unrelated and independently regulated events within the pineal gland. PMID- 2900299 TI - Solubilization kinetics of a triglyceride/n-alkane mixture in a non-ionic surfactant solution. AB - The kinetics of solubilization in a non-ionic surfactant solution of pure n hexadecane, pure triolein and a mixture of the two oils have been investigated. The rates were determined from observations of the dissolution of a single, microscopic droplet, using a drop-on-fibre technique. Conditions were such that negligible saturation of the micellar surfactant with solubilizate occurred. The rate of solubilization of each of the pure oils was found to be independent of time, hexadecane solubilization on a volume basis being about 8 times as rapid as that for triolein. The rate of solubilization of a mixture of the two oils, having a volume fraction 0.69 for triolein, was found to vary in the medium term, the rates apparently being steady both initially and (at a lower value) in the long term. These observations can be related quantitatively to the rates found for the pure oils. PMID- 2900296 TI - Vascular headache. PMID- 2900300 TI - Characterization of sodium carboxymethylcellulose-gelatin complex coacervation by viscosity, turbidity and coacervate wet weight and volume measurements. AB - A sodium carboxymethylcellulose (SCMC) and gelatin coacervation system has been evaluated and characterized and the effects of pH and colloid mixing ratio on the coacervation process investigated. The colloid mixing ratio at which optimum coacervation occurred varied with the coacervation pH. A viscometric investigation of various isohydric SCMC-gelatin mixtures was used to predict optimum conditions for complex coacervation. Optimum coacervation occurred at pH 3.5 at a SCMC-gelatin weight ratio of 3:7 for the SCMC complex coacervation system. Turbidity data confirmed these viscometric results. Coacervate wet weight and volume measurements could not be used to predict optimal coacervation conditions due to changes in the coacervate morphology with mixing ratio. At pH values where coacervation did not occur, the viscosity showed unexpected positive deviations from additive behaviour. PMID- 2900301 TI - Effect of butylated hydroxyanisole on hepatic glucuronidation and biliary excretion of drugs in mice. AB - Inhibition of glucuronidation by depletion of UDP-glucuronic acid from liver impairs the hepatobiliary transport of glucuronidated xenobiotics. However, it is not known if enhancement of hepatic glucuronidation increases the biliary excretion of these compounds. Therefore, the effect of treatment with butylated hydroxyanisole (BHA), which increases hepatic glucuronidation capacity, on the biliary excretion of compounds undergoing glucuronidation was studied in mice. BHA-feeding (1% for 10 days) increased hepatic UDP-glucuronic acid content by 240% and enhanced hepatic UDP-glucuronosyltransferase activities (expressed per kg body weight) toward valproic acid, phenolphthalein, iopanoic acid and bilirubin 220, 180, 120 and 60%, respectively. BHA treatment did not influence the biliary excretion of unmetabolized cholephils, phenol-3,6-dibromphthalein disulphonate and phenolphthalein glucuronide, but enhanced that of phenolphthalein (+108%), iopanoic acid (+63%) and bilirubin (+33%) as glucuronides. However, these increases were apparent only in the initial phase of excretion. In contrast, BHA markedly decreased (-43%) the biliary excretion of valproic acid glucuronides. Simultaneously, BHA increased the urinary excretion of the glucuronides of phenolphthalein (+48%), iopanoic acid (+450%) and valproic acid (+150%). A shift in the distribution of iopanoic acid and valproic acid and metabolites from liver to kidney was also apparent in BHA-fed mice. Thus, enhanced glucuronidation does not facilitate the biliary excretion of all glucuronidated compounds and only transiently increases others. It is likely that this phenomenon is the result of the glucuronides readily entering the plasma and being excreted by the kidney. PMID- 2900302 TI - Biochemical characterization of a new highly cardioselective beta-adrenoceptor antagonist. AB - P0160 (1-phenyl-3-(2-(3-(2-cyanophenoxy)-2-hydroxypropyl)amino) ethylhydantoin HCl) is an aryloxypropanolamine which contains a ureido group as part of the hydantoin ring. This molecule was synthesized to obtain a more cardioselective beta-adrenoceptor blocker. Preliminary data have shown that it is as potent as propranolol and four times more cardioselective than atenolol in pharmacological tests in-vitro and in the conscious rat. In the present study we evaluated the interaction of P0160 with beta-adrenoceptors by radioreceptor binding studies and by measuring adenylate cyclase activity coupled to beta-adrenoceptors. The data indicate that P0160 binds with nanomolar affinity to beta-adrenoceptors labelled with [3H]DHA in the rat heart, but with micromolar affinity in the rat lung. Its binding is stereospecific, the S-(-)isomer being 200 times more active than the R (+) form. P0160's selectivity between cardiac beta 1- and beta 2-receptors was 1388, about 60 times that for metoprolol. Analysis of the thermodynamic characteristics of P0160's interaction with rat heart beta-adrenoceptors indicated antagonist properties of the same order of magnitude as propranolol, as confirmed by adenylate cyclase studies. These data indicate that P0160 is a potent, specific and selective beta 1-adrenoceptor antagonist, and give a molecular explanation for the cardioselective activity found in pharmacological tests. PMID- 2900303 TI - Mechanisms of the antiallergic action of N-methylmequitazine (LG 30435). AB - LG 30435 (N-methylmequitazine) was assayed in passive lung (PLA) and cutaneous (PCA) anaphylaxis in guinea-pigs and rats. At doses from 0.3 to 3 mumol kg-1 i.v., it produced a dose-dependent inhibition of guinea-pig PLA and of rat PCA and PLA, while the parent compound was ineffective or poorly effective up to 3 mumol kg-1. An attempt was made to elucidate the mechanism of LG 30435's action in these anaphylactic models, by means of various antagonists. It was tentatively concluded that different mechanisms are involved in the protective action of LG 30435 in each of the three models: histamine antagonism, possibly accompanied by an inhibition of the effects of peptido-leukotrienes in guinea-pig PLA; histamine antagonism in rat PCA and 5-hydroxytryptamine antagonism in rat PLA, possibly accompanied by a mast-cell stabilizing action in both cases. LG 30435 is devoid of smooth muscle relaxant effects on the airways and its demonstrated anticholinergic and anti-PAF effects do not appear to be involved in its antiallergic action. PMID- 2900304 TI - The use of a perfluorochemical emulsion as a vascular perfusate in drug absorption. AB - In-vitro simultaneous luminal and vascular perfusion using the perfluorochemical emulsion, FC-43 emulsion, as a vascular perfusate, was examined for drug absorption in rat jejunum. The intestinal membrane in this system was found to retain its normal barrier functions for drug transport, as evident from the following: (i) stable absorption clearance of tritiated water and salicylic acid at steady-state, (ii) agreement of this clearance with that by in-situ single pass luminal perfusion, (iii) active transport of D-glucose and its inhibition by phloridzin and (iv) normal glutamate pyruvate transaminase activity in the intestinal mucosa. FC-43 emulsion gave a more normal absorption site blood flow than the usual vascular perfusate containing erythrocytes and albumin in Krebs Henseleit bicarbonate buffer solution. Consequently, this emulsion was useful for examining the contribution of blood flow resistance toward drug absorption. The rate-limiting steps of absorption of tritiated water, antipyrine and salicylic acid were examined by perfusion using FC-43 emulsion. The absorption of tritiated water was almost completely blood flow-limited and its absorption clearance may possibly be an approximated absorption site blood flow. The contribution of blood flow resistance to total resistance for antipyrine absorption exceeded that for salicylic acid absorption. PMID- 2900305 TI - Increase in mouse brain regional noradrenaline turnover after L-dopa administration. AB - Noradrenaline (NA) and its major metabolite, 3-methyl-4-hydroxyphenylethylene glycol (MHPG) were measured by HPLC with electrochemical detection in five mouse brain regions after L-dopa treatment. Noradrenaline concentration increased significantly, by 30-40%, in the three terminal regions of the locus coeruleus; cortex, hippocampus and cerebellum, but did not change in hypothalamus and brainstem. In mice whose central NA levels had been depleted by prior treatment with the neurotoxin, DSP-4, remaining NA neurons in these terminal regions were still able to respond with an increase in NA after L-dopa loading. The NA metabolite, MHPG, increased several-fold in all five regions in both saline and DSP-4-pretreated mice. Thus, L-dopa may be a useful precursor of NA in specific brain regions, particularly when NA is depleted. PMID- 2900306 TI - The response of the intestinal mucosa to prostaglandin E2 during withdrawal from morphine. AB - Experiments were designed to determine whether the diarrhoea characteristic of morphine withdrawal results from an enhanced sensitivity of the intestinal mucosa to PGE2. Rats (250-300 g) were made morphine-dependent by subcutaneous injection of an emulsion releasing 300 mg morphine HCl over 48 h. In-vivo, the transintestinal potential difference (PD) responses to PGE2 (4.6-46 micrograms kg 1 i.v.), which reflect increased Cl secretion, were significantly larger in withdrawn (morphine emulsion, 10 mg kg-1 naloxone s.c.) compared with non dependent animals (emulsion only, naloxone s.c., P less than 0.05). Muscle stripped intestinal sheets from dependent animals incubated with naloxone (10(-5) mol L-1) in-vitro did not demonstrate a greater electrical response (PD, short circuit current) to PGE2 (1.4 x 10(-6) mol L-1) than sheets taken from non dependent animals. In-vitro preparations from animals withdrawn in-vivo did not respond differently from tissue taken from non-dependent animals (naloxone 10 mg kg-1 s.c., 10(-4) mol L-1 in medium, in both groups). This occurred in whole sheets of intestine as well as sheets without attached muscle. Jejunal fluid absorption in-vivo was lower in withdrawn animals than in non-dependent animals. However, the responses to intra-arterial infusion of PGE2 were similar in both groups with 2 micrograms min-1 inhibiting absorption and 4 micrograms min-1 inducing secretion. In-vivo, PGE2-induced Cl secretion appears to be enhanced during withdrawal although net fluid transport is not altered, suggesting different effects of the withdrawal process on the electrogenic Cl secretory and neutral NaCl absorptive mechanisms. PMID- 2900307 TI - The biochemical actions of phentolamine and papaverine on rat perfused skeletal muscle. AB - The direct actions of the vasodilators, papaverine and phentolamine, on skeletal muscle metabolism were investigated in an isolated perfusion system. Eviscerated male rats were hemisected above the diaphragm and perfused, via the aorta, with a physiological perfusion medium containing erythrocytes. Papaverine, but not phentolamine, reduced vascular resistance throughout the 80 min study. Papaverine caused marked reductions in muscle concentrations of ATP and phosphocreatine, when compared with muscle from preparations without added vasodilators. This was accompanied by elevations in lactate concentrations. Water content of papaverine treated muscle was also higher than values in unperfused muscle taken in-vivo. Phentolamine, in contrast, had no effect on muscle ATP, phosphocreatine, lactate or water content. The metabolism of the entire preparation was also investigated. Papaverine induced increases in lactate output while phentolamine treatment caused an initial uptake, followed by an increased output of lactate. There was no significant effect of either papaverine or phentolamine on the metabolism of K+ and glucose. Arteriovenous differences in oxygen-saturation of haemoglobin and pH were also unaltered. Investigations on aspects of protein metabolism demonstrated that papaverine and phentolamine caused significant reductions in muscle protein synthesis when compared with control perfusions or in-vivo values. The reductions in synthesis were not due to reductions in cAMP or limitations in branched-chain amino acid supply. However, there was the suggestion that phentolamine caused a decrease in protein breakdown. The overall data indicated that papaverine and phentolamine may cause impairment of skeletal muscle metabolism. This has important implications for their therapeutic or experimental use. PMID- 2900308 TI - Inhibitory effect of glycyrrhetinic acid derivatives on arachidonic acid-induced mouse ear oedema. AB - The inhibitory effects of glycyrrhetinic acid and its derivatives were examined on arachidonic acid (AA)-induced ear oedema in mice. Of the compounds, dihemiphthalate derivatives of 18 beta-olean-12-ene-3 beta, 30-diol (IId, IId'), 18 beta-olean-9(11)12-diene-3 beta, 30-diol (IIIa, IIIa') and olean-11, 13(18) diene-3 beta, 30-diol (IVa, IVa') showed a strong inhibition of ear oedema on both tropical (ID50, 1.9, 2.8 and 1.7 mg/ear, respectively) and oral (ID50, 90, 130 and 88 mg kg-1, respectively) administration. Topical ID50 values were approximately the same potency as nordihydroguaiaretic acid (ID50, 2.1 mg/ear). Given topically these compounds were also capable of inhibiting PGE2 and LTC4 formation at an early stage of AA-induced ear oedema. However, glycyrrhetinic acid (Ia) and deoxoglycyrrhetol (IIa), the fundamental skeletons of the derivatives, showed no detectable inhibition of oedema at a dose of 1 mg/ear (topical) or 200 mg kg-1 (oral). The most effective time for the topical administration of the compound IId against ear oedema was 0-30 min before AA application; this is different from dexamethasone which requires a time lag for reaction. The results suggest that the inhibitory effect of the hemiphthalate compounds (IId, IId', IIIa, IIIa', IVa and IVa') is a direct action, and does not involve the anti-inflammatory action of steroids mediated by the secondary formation of a reactive protein. PMID- 2900309 TI - The effects of interacting variables on the tensile strength, disintegration and dissolution of paracetamol tablets. AB - A factorially designed scheme has been used to analyse the separate and combined effects of packing fraction (P), nature of binder (N) and concentration of binder (C) on the tensile strength, disintegration and dissolution (t50%) times of paracetamol tablets. In general, P has the greatest effect on tensile strength, disintegration and dissolution times followed by C then N. For the variables in combination, the ranking of the effects on tensile strength, for the PVP/gelatin formulations, are P x N greater than N x C greater than P x C and for the PVP/tapioca formulations are P x C = N x C greater than P x N. For disintegration and for dissolution, the ranking for the PVP/gelatin formulations are P x C greater than P x N = N x C and P x N greater than P x C greater than N x C, respectively, and for the PVP/tapioca formulations are P x N greater than N x C = P x C. The results also show that tapioca acts as a binding agent when included in paracetamol tablet formulations, but it is a weaker binder than either PVP or gelatin. It is thus required in a higher concentration to produce tablets of comparable physical properties with those formulated with PVP or gelatin. PMID- 2900310 TI - Investigation into substrate cracking of a film-coated bilayered tablet. AB - Substrate cracking occurred during film coating of a bilayered tablet. The cause was traced to differences in the expansion characteristics of the two layers upon exposure to heat. Thermal mechanical analysis was used to determine the coefficients of thermal expansion of the respective layers. PMID- 2900311 TI - Pharmacokinetic evaluation of local drug delivery: the intratesticular and intrarenal administration of acenocoumarol in the rat. AB - According to theory, the regional increase in drug concentration during target organ directed drug delivery as compared with systemic drug delivery is related to the quotient of the clearance of the drug and the blood flow of the target organ. We investigated the steady-state pharmacokinetic disposition of S acenocoumarol in plasma, liver, testis, and kidney following its administration (constant rate infusion by an osmotic minipump) directly into the testis or the kidney of rats. The effects of clearance induction (phenobarbitone treatment) on the disposition of the drug were also investigated. The results confirm the theory of target-directed drug delivery. PMID- 2900312 TI - The effect of hydrochlorothiazide on the composition of renal papillary interstitial fluid in the rat. AB - The effect of chronic hydrochlorothiazide administration on the composition of renal papillary interstitial fluid was investigated in the rat. Hydrochlorothiazide alone had no effect on papillary composition. However, when the sodium depletion that usually accompanies thiazide treatment was minimized by allowing the rats access to hypertonic NaCl solution, hydrochlorothiazide administration resulted in significant reductions in papillary osmolality, and sodium and potassium concentrations. It is suggested that the effects of hydrochlorothiazide on the renal papilla might be mediated by thiazide-induced hypokalaemia, and that under normal circumstances these effects are masked by the concomitant sodium depletion. PMID- 2900313 TI - Binding studies on two functional cardioselective antimuscarinic compounds. AB - Vecuronium and himbacine are antimuscarinic compounds which in functional studies exhibited a ca 6- and 10-fold higher potency at cardiac muscarinic receptors than at ileal muscarinic receptors. However in binding studies both compounds failed to differentiate between [3H](-)-QNB binding sites in guinea-pig atrial and ileal muscle homogenates. In the latter experiments, the dissociation constants of vecuronium in atria and ileum and that of himbacine in ileum were lower than the values determined functionally. The basis for the lack of cardioselectivity in binding studies is not known. These compounds add to the list of functional cardioselective muscarinic receptor antagonists that failed to display selectivity in binding studies with [3H](-)-QNB. PMID- 2900314 TI - Twenty-one hormones fail to inhibit the brain to blood transport system for Tyr MIF-1 and the enkephalins in mice. AB - Tyr-MIF-1 (Tyr-Pro-Leu-Gly-amide) and methionine enkephalin are transported intact across the blood-brain barrier by a saturable, stereospecific system. This system has been found to be modulated by a few non-peptide substances and by certain conditions such as ageing and some stresses. We investigated the possibility that hormones structurally unrelated to Tyr-MIF-1 and the enkephalins might also be capable of modulating this transport. Twenty-one hormones were tested including steroids, proteins, glycoproteins, peptides, and thyroid hormones, in doses ranging from 0.01 pmol to 1 nmol/mouse by injecting each hormone directly into the lateral ventricle simultaneously with [125I]Tyr-MIF-1. No clear effect on transport could be established for any of the substances at the doses tested. None of these substances seemed able to act as competitive inhibitors, to share their respective transport systems with Tyr-MIF-1, or to modulate immediately the saturable transport system. PMID- 2900315 TI - Differential displacement of opioids from plasma protein binding sites by di isopropylfluorophosphate in the mouse. AB - Di-isopropylfluorophosphate (DFP) displaced the opioid drug, alfentanil, from plasma proteins in-vivo and in-vitro in mice but was without effect on the structurally related compound, fentanyl. This action probably accounts for the enhanced entry of alfentanil into the brain of DFP-treated animals and its enhanced antinociceptive activity. PMID- 2900316 TI - Flavonoids, leucocyte migration and eicosanoids. AB - Quercetin reduced the concentration of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the pleural exudate induced in rats by 1% carrageenan given intrapleurally. Leucocyte migration in the exudate was also reduced by the flavonoid. Inhibition of eicosanoids and leucocytes in the exudate was dose related. Quercetin also reduced LTB4 synthesis in cells stimulated with ionophore A23187, either ex-vivo or in-vitro. A similar, though less active, mode of action was found with quercitrin, while apigenin and luteolin reduced leucocyte accumulation and PGE2 formation, but not LTB4-formation. PMID- 2900317 TI - Oral absorption of metronidazole in rabbits irradiated with cobalt-60 gamma radiation. AB - The absorption of oral metronidazole in control rabbits and in rabbits irradiated with cobalt-60 gamma radiation was studied. It was observed that the bioavailability of metronidazole was significantly reduced in irradiated animals the reduction being dependent on the dose of radiation. The maximum decrease in absorption was seen 48 h post-irradiation. PMID- 2900318 TI - Naltrexone and the behavioural action of clonidine in normotensive and spontaneously hypertensive rats. AB - The present experiments were aimed at the behavioural effects of clonidine and the possible involvement of opiate systems therein. Previous work had shown that opiate antagonists could block the effects of clonidine on blood pressure. In the open-field, clonidine treatment induced a decrease in ambulation and rearing activity. This effect was similar in normotensive Wistar and Wistar-Kyoto rats and in spontaneously hypertensive rats. In neither strain did naltrexone pretreatment influence the behavioural action of clonidine, however. These results do not lend support to the proposed interaction between opiate systems and the central effects of clonidine. PMID- 2900319 TI - Zacopride, a potent 5-HT3 antagonist. AB - The substituted benzamide derivative zacopride was found to antagonize competitively the effects of 5-hydroxytryptamine (5-HT) on the guinea-pig ileum, the rabbit vagus nerve and the von Bezold Jarisch reflex in the rat. The potency of zacopride was comparable with that of ICS 205-930 and it is concluded that zacopride possesses 5-HT3 receptor antagonizing properties. PMID- 2900320 TI - Zacopride: anxiolytic profile in rodent and primate models of anxiety. AB - Zacopride, a substituted benzamide derivative, was compared with diazepam in three models of experimental or provoked anxiety. The drug's action (i) in reducing aversion to a brightly lit environment was assessed in mice using a two compartment black and white test box system, (ii) in disinhibiting a suppressed behaviour was measured in the rat social interaction test under high light/unfamiliar conditions and (iii) in antagonizing a defensive response in the marmoset was assessed using the threat of a human presence. Both zacopride and diazepam enhanced exploratory behaviour and social interaction in the mouse and rat models and antagonized the defensive response in the marmoset, zacopride being 100 times more potent than diazepam. It is concluded that the 5-HT3 receptor antagonist, zacopride, alters rodent and primate behaviour in a manner consistent with that of an anxiolytic agent. PMID- 2900321 TI - Anticholinesterase activity of prolactin: correlation with analgesia. AB - The possible inhibitory effect of prolactin on serum cholinesterase activity has been examined. Prolactin given to mice inhibited the enzyme's activity in a dose related fashion. This inhibition was not reversed by naloxone. A significant correlation was observed between the anticholinesterase and analgesic activity of prolactin. The findings suggest that prolactin may exert its cholinomimetic activity by inhibition of cholinesterase. A significant contribution by the cholinergic activity, which was independent of the opioid system, was indicated in the analgesic effect. PMID- 2900322 TI - Dopamine and apomorphine do not modulate the uptake of [3H]D-aspartate in the rat striatum in-vitro. AB - Sodium-dependent [3H]D-aspartate uptake was measured in rat striatal homogenates. The uptake was inhibited by both L- and D-glutamate, with IC50 values of 5.6 and 224 microM, respectively. Dopamine (10(-7)-10(-4) M), apomorphine (10(-7) M), sulpiride (10(-6) M) or a combination of dopamine and sulpiride were found not to affect the observed uptake of [3H]D-aspartate. Thus, the in-vitro dopaminergic modulation of high affinity glutamate uptake reported in the literature is not found when [3H]D-aspartate is used instead of [3H]L-glutamate. PMID- 2900323 TI - Degloving injuries of the foot. Case presentation and review of the literature. PMID- 2900324 TI - Antinociceptive action of intracerebroventricularly administered dynorphin and other opioid peptides in the rat. AB - Using a rat tail-flick analgesic assay that uses a cold water-ethylene glycol mixture (-10 degrees C) as the noxious stimulus, we have been able to demonstrate a dose-related, naloxone-reversible analgesic effect for dynorphin A (1-17), the proposed endogenous ligand for the kappa receptor. Male Sprague-Dawley rats were implanted surgically with cannulas in the right lateral ventricle at least 1 week before testing. Five microliters of either drug or saline, followed by a 3 microliter saline flush, were administered. Nociceptive threshold was measured as the latency for the rat to flick or remove its tail from the bath solution after immersion. Dynorphin produced a dose-related analgesia at doses of 1 to 50 micrograms i.c.v., reaching 100% maximum possible analgesia (compared to predrug base line) at the highest dose. We found similar dose-related analgesia when we tested the selective mu agonist [Try-D-Ala-Gly-NMe-Phe-Gly-ol] (0.01-1 microgram), the selective kappa receptor ligand U-50,488H (100-500 micrograms), the selective delta agonist [D-Pen2,5]-enkephalin (50-200 micrograms) and beta endorphin (0.1-10 micrograms). Naloxone (1.0 mg/kg) was able to block the antinociceptive effect of all but the highest doses of dynorphin, which required 10.0 mg/kg of naloxone. When we compared the same dosages of dynorphin using hot water (55 degrees C) as the noxious stimulus, no antinociception was observed. Although we do not known the mechanisms responsible for the differences between the hot and cold water tests, it may be that the cold water tail-flick test, which is able to assess the antinociceptive activity of both opioid agonists and mixed agonist-antagonists, is a more sensitive measure of the type of analgesia mediated by kappa receptors. PMID- 2900325 TI - Cardiovascular effects of cocaine in conscious dogs: importance of fully functional autonomic and central nervous systems. AB - The cardiovascular effects of i.v. cocaine were studied in conscious dogs with chronically implanted arterial and venous catheters. The effects of i.v. cocaine on arterial blood pressure, heart rate and rate-pressure product were studied at doses ranging from 0.063 to 8 mg/kg. To avoid any possibility that development of acute tolerance to the actions of cocaine might interfere with our results, each dose of cocaine was administered on a separate day. Cocaine-induced changes in mean arterial blood pressure ranged from an increase of 11.8 +/- 2.1 mmHg at a dose of 0.063 mg/kg to an increase of 95.8 +/- 11 mmHg at a dose of 8 mg/kg. Similarly, cocaine-induced changes in heart rate ranged from a decrease of 4.5 +/ 0.9 beats/min to an increase of 83 +/- 10 beats/min at the 0.063 and 8 mg/kg cocaine doses, respectively. Although the rate-pressure product was not significantly altered by doses of cocaine below 0.25 mg/kg, doses above that level produced dose-dependent increases in this parameter. The rate-pressure product, which was increased approximately 27% by the 0.25 mg/kg dose of cocaine, was more than doubled by the 2 mg/kg cocaine dose and was increased almost 4-fold by the 8 mg/kg dose of cocaine. The blood pressure response observed after cocaine administration was significantly decreased by pretreatment with 10 mg/kg hexamethonium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900326 TI - Influence of dynorphin (1-13) on spinal reflexes in the rat. AB - Previously, we showed that intrathecal administration of dynorphin A (1-13) (dynorphin) in rats produced, within 5 min, a reversible inhibition of tail-shock vocalization, a reversible hind-limb paralysis and an irreversible loss of the tail-flick reflex. The selective loss of the tail-flick reflex was investigated using electrophysiologic methods and a dose of dynorphin effective in 90% of the rats. These studies revealed that intrathecal administration of dynorphin resulted in loss of the C-fiber initiated reflex when assayed 1 to 30 days after injection. On the other hand, reflexes initiated by Group I and III afferents were not obviously different from those seen in saline-injected animals. Application of dynorphin in situ on to the cord during stimulation of the dorsal root and recording of ventral root potentials demonstrated a rapid onset of peptide action. Initially the C-fiber evoked reflex was potentiated selectively with a decrease in conduction time. These responses were followed by inhibition of all reflexes for a short period of time after which the reflexes initiated by Group I and III afferents reappeared whereas the C-fiber reflex did not recover. This time course paralleled closely the time course of the loss of the tail-flick reflex suggesting that the two effects may be causally related. Furthermore, the selective N-methyl-D-aspartate antagonist DL-2-amino-5-phosphonovalerate applied directly to the spinal cord during recording resulted in a reversible inhibition of the C-fiber-initiated reflex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900327 TI - Noradrenergic denervation alters serotonin2-mediated behavior but not serotonin2 receptor number in rats: modulatory role of beta adrenergic receptors. AB - Recent behavioral evidence suggests that enhancement of noradrenergic neurotransmission may alter the functional sensitivity of serotonin2 (5-HT2) receptors in the central nervous system. The present studies have examined the effects of two types of noradrenergic denervation [neurotoxic: via N-(2 chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) treatment; and pharmacologic: via chronic beta adrenergic receptor blockade] on the 5-HT2-mediated head shake response and cortical beta adrenergic and 5-HT2 receptor number in the rat. No changes in quipazine-induced head shakes were observed 3 days after DSP4 lesion. However, the frequency of head shakes was significantly enhanced 10 days after DSP4 treatment in the presence of a 39% up-regulation of beta adrenergic receptors. Pretreatment with propranolol 10 days after DSP4 lesion selectively antagonized the enhancement of the behavioral response to quipazine without altering base-line response rate, whereas pretreatment with the 5-HT2 antagonist ketanserin totally blocked head shakes in both control and DSP4-treated rats. Pharmacologic denervation achieved by continuous (14 day) administration of the beta adrenergic antagonist propranolol also resulted in a potentiation of the head shake response (274% of control) and an upregulation of beta adrenergic receptors (44%). Conversely, continuous treatment with the beta adrenergic agonist clenbuterol resulted in a marked reduction in head shakes (36% of control) with a concomitant 29% down-regulation of beta adrenergic receptors. 5 HT2 receptor binding was not modified by either DSP4 lesion or continuous administration of beta adrenergic agonists or antagonists. These studies demonstrate that changes in cortical beta adrenergic receptor density may modify 5-HT2-mediated behavior in a manner that is independent of changes in 5-HT2 receptor number. PMID- 2900328 TI - The beta adrenoceptor blocker tertatolol causes vasodilatation in the isolated perfused vasoconstricted rat kidney. AB - The activity of the beta adrenoceptor antagonist tertatolol on renal vasoconstrictions was investigated. Infusion of increasing concentrations of tertatolol (10(-8) to 10(-5) M) progressively inhibited the constrictor responses to bolus injections of norepinephrine and to electrical stimulation in isolated perfused kidneys of both normotensive and spontaneously hypertensive rats. Also, in kidneys of normotensive rats the vasoconstrictions caused by serotonin and barium chloride were inhibited by tertatolol. During sustained vasoconstrictions induced by infusion of norepinephrine (6 X 10(-7) M) increasing doses of tertatolol (2.5 X 10(-7) g to 2 X 10(-5) g) caused rapid, reversible dilatations in the rat kidneys. The inhibitory responses caused by tertatolol were not antagonized by propranolol, atropine, hexamethonium, SCH23390, metoclopramide, mepyramine, cimetidine, naloxone, cocaine or indomethacin. During constrictions caused by norepinephrine, methylene blue significantly inhibited the renal vasodilatations caused by tertatolol, acetylcholine, papaverine and nitroglycerin but not those caused by atrial natriuretic factor. Unlike the other vasodilators, tertatolol did not inhibit the constrictions induced by prostaglandin F2 alpha (5 X 10(-6) M) in the rat kidneys. In canine renal arteries with endothelium, tertatolol (10(-9) to 10(-5) M) did not cause relaxations during contractions induced by norepinephrine, electrical stimulation or prostaglandin F2 alpha. Our data illustrate that tertatolol has potent vasodilator properties in the isolated perfused vasoconstricted rat kidney. The dilator response to the beta blocker cannot be inhibited by a variety of classical receptor blockers but ultimately seems to depend on the formation of cyclic GMP. PMID- 2900329 TI - Cardioprotective action of alpha-blocking agents, phentolamine and bunazosin, on hypoxic and reoxygenated myocardium. AB - The present study was undertaken to determine whether alpha-blocking agents, phentolamine and bunazosin, may exert a cardioprotective effect on hypoxic and subsequently reoxygenated hearts. For this purpose, rabbit hearts were perfused for 20 min under hypoxic conditions, followed by a 45 min-reoxygenation. Agents were administered between the 8th and 20th min of hypoxic perfusion. Hypoxic perfusion for 8 min resulted in a decline of cardiac contractile force and myocardial high-energy phosphates and a loss of adenine nucleotide metabolites from the heart, whereas a rise in resting tension was not observed. Neither increase in perfusion pressure, release of creatine kinase from hearts nor increase in tissue calcium was observed. At 20 min-hypoxia, significant changes in resting tension and perfusion pressure of the heart and release of creatine kinase from the heart were observed. Cardiac contractile force after 45 min of reoxygenation was less than 10% of the initial value. Treatment with 83 microM phentolamine or 46 microM of bunazosin resulted in a significant suppression of hypoxia-induced increase in tissue calcium, release of creatine kinase and adenine nucleotide metabolites and rise in perfusion pressure and resting tension. Treatment with either phentolamine or bunazosin resulted in appreciable recovery of cardiac contractile force. Reoxygenation-induced release of creatine kinase was also suppressed significantly. Two possible mechanisms for the protective effect of this treatment are considered; 1) preservation of ATP metabolites which may be utilized as substrates for a salvage synthesis of ATP during reoxygenation and 2) prevention of a nonselective transmembrane flux of cellular constituents due to changes in cell membrane permeability. PMID- 2900330 TI - Comparative effects of alpha-1 and alpha-2 adrenoceptors in modulation of coronary flow during exercise. AB - During submaximal exercise, an alpha adrenergic vasoconstriction that opposes metabolic dilation exists in the coronary circulation. Fifteen dogs were given i.c. injections of prazosin (0.5 mg) or yohimbine (0.7 mg) to determine the participation of alpha 1 and alpha 2 adrenoceptors in the vasoconstriction during exercise. All dogs were chronically instrumented to measure left circumflex blood flow, heart rate, regional left ventricular function and global left ventricular function. The experimental protocol consisted of a graded exercise regimen during which, at the highest level of exercise an alpha antagonist was given i.c. Exercise significantly increased heart rate, left ventricular pressure, dP/dt, systolic shortening and rate of shortening, and coronary blood flow. After the prazosin injection there was an increase in circumflex blood flow (25 +/- 3%) as well as regional (38 +/- 6%) and global (20 +/- 3%) contractile function. However, there was no change in circumflex blood flow or myocardial function after yohimbine. These data indicate that during exercise the sympathetic constrictor tone in the coronary circulation is mediated primarily by alpha 1 adrenoceptors, with little or no involvement from alpha 2 adrenoceptors. PMID- 2900331 TI - Pertussis toxin modifies the characteristics of both the inhibitory GTP binding proteins and the somatostatin receptor in anterior pituitary tumor cells. AB - The effects of pertussis toxin treatment on the characteristics of somatostatin receptors in the anterior pituitary tumor cell line AtT-20 were examined. Pertussis toxin selectively catalyzed the ADP ribosylation of the alpha subunits of the inhibitory GTP binding proteins in AtT-20 cells. Toxin treatment abolished somatostatin inhibition of forskolin-stimulated adenylyl cyclase activity and somatostatin stimulation of GTPase activity. To examine the effects of pertussis toxin treatment on the characteristics of the somatostatin receptor, the receptor was labeled by the somatostatin analog [125I]CGP 23996. [125I]CGP 23996 binding to AtT-20 cell membranes was saturable and within a limited concentration range was to a single high affinity site. Pertussis toxin treatment reduced the apparent density of the high affinity [125I]CGP 23996 binding sites in AtT-20 cell membranes. Inhibition of [125I]CGP 23996 binding by a wide concentration range of CGP 23996 revealed the presence of two binding sites. GTP predominantly reduced the level of high affinity sites in control membranes. Pertussis toxin treatment also diminished the amount of high affinity sites. GTP did not affect [125I]CGP 23996 binding in the pertussis toxin-treated membranes. The high affinity somatostatin receptors were covalently labeled with [125I] CGP 23996 and the photoactivated crosslinking agent n-hydroxysuccinimidyl-4-azidobenzoate. No high affinity somatostatin receptors, covalently bound to [125I]CGP 23996, were detected in the pertussis toxin-treated membranes. These results are most consistent with pertussis toxin uncoupling the inhibitory G proteins from the somatostatin receptor thereby converting the receptor from a mixed population of high and low affinity sites to only low affinity receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900332 TI - Synaptic activation of N-methyl-D-aspartate receptors in the Schaffer collateral commissural pathway of rat hippocampus. AB - 1. The involvement of N-methyl-D-aspartate (NMDA) receptors in the response to single-shock (0.033 Hz) stimulation of the Schaffer collateral-commissural pathway in hippocampal slices has been investigated using current- and voltage clamp techniques. 2. In the presence of Mg2+ (1 or 2 mM) at membrane potentials near rest, the selective NMDA antagonist D-2-amino-5-phosphonovalerate (APV) had no effect on the excitatory postsynaptic potential (EPSP) and the biphasic inhibitory postsynaptic potential (IPSP) evoked by Schaffer collateral commissural stimulation. The recurrent IPSP evoked by antidromic stimulation of alvear fibres was also unaffected by APV. 3. The introduction of a Mg2+-free perfusate led, at high stimulus intensity, to an orthodromically evoked epileptiform discharge but little change in the recurrent IPSP. APV suppressed a large proportion of the enhanced response in Mg2+-free perfusate. 4. EPSPs and excitatory postsynaptic currents (EPSCs) evoked in Mg2+-free perfusate invariably had both APV-resistant and APV-sensitive components. Both synaptic components had similar thresholds and latencies to onset. The APV-sensitive component had a long time to peak and long duration. 5. Under current-clamp conditions in Mg2+ containing medium, an APV-sensitive component was recorded at membrane potentials of between -30 and -10 mV, but not at potentials more negative than -55 mV. 6. Under voltage-clamp, but not current-clamp, conditions in Mg2+-containing medium, a small APV-sensitive component was recorded at resting membrane potentials and increased with membrane depolarization. The difference between the current- and voltage-clamp data is attributed to the hyperpolarizing influence of conjointly activated IPSPs. 7. In the presence of Mg2+ and picrotoxin, a dual-component EPSC was recorded between -30 and +30 mV in all cells examined. The APV-resistant and APV-sensitive components had similar latencies to onset. They both had reversal potentials of between -8 and 0 mV. The APV-sensitive component had a longer latency to peak and duration than the APV-resistant component. 8. It is suggested that NMDA receptors can contribute a low-threshold and long-duration monosynaptic component of the response evoked by low-frequency stimulation of the Schaffer collateral-commissural pathway. However, under physiological conditions significant expression of this component is prevented by concurrently activated IPSPs which rapidly hyperpolarize neurones into a region where Mg2+ substantially blocks NMDA channels. PMID- 2900334 TI - Electrical activity at the sympathetic neuroeffector junction in the guinea-pig vas deferens. AB - 1. The relationship between the nerve terminal action potential and transmitter release from sympathetic postganglionic nerve terminals has been studied in vitro by focal extracellular recording. 2. In the absence of stimulation, 'spontaneous excitatory junction currents' (SEJCs) were recorded with amplitudes up to 500 microV, durations of 50-80 ms and frequencies of occurrence of 0.3-0.05 Hz; SEJCs of unusually long time course were also observed. The SEJCs were not recorded in tissues pre-treated with 6-hydroxydopamine to destroy sympathetic nerves, were unaffected by tetrodotoxin (TTX), the competitive alpha-adrenoceptor antagonists, prazosin and phentolamine, the irreversible alpha-adrenoceptor antagonist benextramine but were blocked by alpha,beta-methylene ATP which desensitizes P2 purinoceptors. 3. During trains of supramaximal stimuli at 0.1-4 Hz stimulus locked 'excitatory junction currents' (EJCs) were evoked intermittently from the population of varicosities located under the suction electrode with a probability of occurrence of 0.005-0.8. Although EJCs occurred intermittently, they were always preceded by an associated, non-intermittent, nerve impulse (delay less than or equal to 3 ms). 4. The EJCs reflect transmitter release from nerves because they were abolished by TTX, removal of calcium from the bathing medium, exposure to alpha-beta-methylene ATP and exhibited frequency-dependent facilitation. 5. Amplitude distributions of SEJCs and EJCs recorded in the same attachment were similar and skewed towards low-amplitude events. Individual SEJCs and EJCs could be found which were identical in amplitude and time course. 6. Locally applied TTX blocked impulse propagation and transmitter release in the terminal region; electrotonic invasion of the terminals from the point of block did not activate the transmitter release process. 7. These studies indicate that (1) intermittence of transmitter release is caused by a low probability of release in the invaded varicosity and is not caused by conduction failure in the terminal regions, (2) only a single quantum is normally secreted when the release mechanism of a varicosity is activated by the nerve impulse and (3) active invasion of the terminals is necessary for transmitter release to occur. PMID- 2900333 TI - Frequency-dependent N-methyl-D-aspartate receptor-mediated synaptic transmission in rat hippocampus. AB - 1. The effects of the N-methyl-D-aspartate (NMDA) antagonist, D-2-amino-5 phosphonovalerate (APV) were examined on synaptic responses evoked by high frequency stimulation of the Schaffer collateral-commissural pathway, in the presence of Mg2+ (1 or 2 mM) and functional synaptic inhibition. 2. The synaptic response evoked by 100 Hz stimulation comprised fast excitatory postsynaptic potentials (EPSPs) evoked by each shock and a slow depolarization. APV reduced the size of the depolarization without depressing the fast EPSPs. 3. The mean (+/ 1 S.E.) amplitude of the APV-sensitive component (3.0 +/- 0.3 mV), evoked by 100 Hz stimulation at membrane potentials near rest, was invariably smaller than the first fast EPSP (9.8 +/- 0.7 mV). Both of these synaptic components had similar thresholds and increased in amplitude as the stimulus intensity was raised. There was a positive correlation between the amplitude of the two components (r = 0.57, P less than 0.01). 4. The amplitude of the APV-sensitive component was positively correlated (r = 0.97, P less than 0.05) with the frequency of stimulation during the trains (between 10 and 100 Hz). The threshold frequency for evoking an APV sensitive component was approximately 10 Hz. 5. In contrast to the fast EPSPs the amplitude of the APV-sensitive component increased with depolarization, and decreased with hyperpolarization, of a neurone from its resting membrane potential. The component was no longer present in some cells which had been hyperpolarized sufficiently. 6. It is suggested that during high-frequency stimulation a neurone may become depolarized for a sufficient time to reduce the Mg2+ block of NMDA channels. This enables the NMDA receptor system to contribute transiently to the synaptic response, despite the inhibitory synaptic mechanisms which prevent its activation during single-shock stimulation. The characteristics of the NMDA receptor-mediated synaptic response may explain properties relating to the induction of long-term potentiation (LTP). PMID- 2900335 TI - Midline cerebral defects and Kallmann's syndrome. PMID- 2900337 TI - A predevelopment mosquito survey in the Mahaweli Development Project area, Sri Lanka: adults. PMID- 2900336 TI - Giant gastrinoma in a patient with multiple endocrine adenopathy (type 1). PMID- 2900338 TI - A predevelopment mosquito survey in the Mahaweli Development Project area, Sri Lanka: immatures. PMID- 2900339 TI - Efficacy of a single dose of secnidazole in the treatment of acute and chronic amoebiasis. AB - An open study was carried out to determine the clinical efficacy of secnidazole in the treatment of acute and chronic cases of amoebiasis. Patients were given 2 g of secnidazole in a single dose or in two divided doses within a 4 h interval. Details were recorded daily by patients of complaints such as fever, lumbar pain, LBM, dizziness, body weakness, bloody mucoid stools, epigastric pains and other symptoms, before and after treatment. Results were analysed for 45 chronic and five acute cases and showed clinical cure of 98% in chronic and 80% in acute cases. The acute group showed a non-significant change (P greater than 0.05) which could be attributed to the small sample size. The treatment regimen proved effective for the eradication of E. histolytica and only two (4%) remained positive after treatment out of the 50 patients initially positive. PMID- 2900340 TI - Observations on the interpretation of amoebic serology in endemic areas. AB - Antibody to Entamoeba histolytica antigen was evaluated in cases of proven and suspected intestinal amoebiasis as well as in extra-intestinal cases from an endemic area. Screening methods included the gel diffusion precipitation test (GD), counter immunoelectrophoresis (CIE) and the indirect haemagglutination test (IHA). Control populations consisting of asymptomatic cyst passers, non-amoebic individuals, patients with giardiasis and cases of enteric fever were also screened using the above tests. All (100%) cases of amoebic liver abscess and 75 80% of hepatic amoebiasis without overt abscess formation could be detected by serology, with good correlation between the tests used. However, the interpretation of serology in cases of proven and suspected intestinal amoebiasis posed two main problems. The presence of low antibody levels even in proven cases and the persistence of antibodies due to past infection was found to reduce the diagnostic efficiency of serology for acute intestinal amoebiasis. There was no statistical difference between intestinal cases and controls when comparing either percentage of cases detected or titre of antibody obtained. The results of this study indicate that serology for acute intestinal amoebiasis can be unreliable; however, it is of undoubted value as an adjunct to clinical diagnosis in cases of hepatic amoebiasis. PMID- 2900342 TI - [Progress in the study of lipoprotein metabolism and atherosclerosis: progress in the molecular genetic study of apolipoproteins and hyperlipidemia]. PMID- 2900343 TI - [Endogenous C-type retroviridae and autoimmune diseases]. PMID- 2900341 TI - Immunological analysis of host and agent effects on Creutzfeldt-Jakob disease and scrapie prion proteins. AB - Creutzfeldt-Jakob disease (CJD) and scrapie are degenerative neurological diseases caused by unusual infectious pathogens. The term prion has been introduced to underscore the apparent distinctness of these agents from viruses and viroids. The only macromolecule shown to be associated with the infectious agent, the CJD or scrapie prion protein (PrPCJD or PrPSc, respectively), is encoded by the same gene as a normal cellular protein. In several studies biochemical differences have been reported in PrPScs derived from a common host species infected with different putative strains of the scrapie agent, suggesting agent-specific characteristics independent of the host. We analyzed various agent host combinations by Western blotting of PrPs that were separated by size or charge. The profile of immunoreactive proteins for CJD prions isolated from mice, guinea pigs, and humans appeared distinct. Importantly, PrPCJDS purified from a human brain and from the corresponding first-passage mouse brains were clearly distinguishable. PrPCJDs isolated from CJD prions propagated in NAMRU or B10.Q mice, which are homozygous for a short-incubation-time gene; from the short incubation-time backcross progeny of (B10.Q x I/LnJ)F1 x B10.Q; or from NAMRU mice inoculated with I/LnJ prions were identical to each other but distinguishable from those of I/LnJ mice, which are homozygous for the long incubation-time gene. The PrPs from human CJD and ovine scrapie propagated in the same mouse strain appeared the same, but they were distinct from the same isolate of scrapie passaged in hamsters. Lastly, PrPScs purified from five different strains of scrapie propagated in C57BL mice were identical, including strains, ME7 and 139A, which were previously reported to be distinct. This evidence does not support, although it does not exclude, agent-mediated characteristics independent of host-mediated ones for scrapie and CJD. PMID- 2900344 TI - [Marker antibodies of autoimmune diseases and their clinical significance]. PMID- 2900345 TI - [Clinical study of autoimmune diseases: recent trends--with special reference to progress in immunological tests and therapeutic methods. Systemic autoimmune diseases. 5) Periarteritis nodosa and necrotic vasculitis]. PMID- 2900346 TI - PstI fragment polymorphism in the gene of the human ATP synthase beta subunit. PMID- 2900347 TI - [Effect of beta-blockers on retinal function in vitro]. AB - In an attempt to identify possible beta-adrenergic mechanisms in the cat retina the authors extended their previous studies on the effects of beta-agonists (Graefe's Arch. clin. exp. Ophthalmol. 225: 33-38, 1987) to three beta-adrenergic antagonists: propranolol, ICI 118.551, and timolol were applied in micromolar concentrations to the arterially perfused, dark-adapted cat eye. The rod ERG b wave was generally depressed, sometimes enhanced after initial depression (propranolol), without showing any clear-cut dose-dependency. In contrast, the rod-mediated optic nerve action potential exhibited dose-dependent depression of the plateau and OFF components. All effects were reversible within 60-80 minutes. These results, in conjunction with earlier data on the effects of beta-agonists and recent biochemical and autoradiographic studies, strongly support the theory that there are beta-adrenergic synaptic mechanisms located in the inner layers of the mammalian retina. PMID- 2900348 TI - Effects of low amine diet on gastric endocrine cell proliferation in the rat. AB - The effects of a liquid diet low in amines on gastrin cell and somatostatin cell functions were studied in the rat. Significant decreases in portal gastrin levels (44% at 5 days) were noted in animals maintained on a liquid diet (Vivonex). Refeeding solid rat chow resulted in a significant, but transient, hypergastrinemia. Portal somatostatin levels were significantly increased during ingestion of the liquid diet. With refeeding, portal somatostatin promptly returned to baseline values. Gastrin cell density decreased progressively during liquid diet ingestion (37% decline by Day 5). Antral somatostatin cell numbers were increased during this time period (86% versus controls). With solid chow refeeding, both gastrin cell and somatostatin cell densities returned to baseline. PMID- 2900349 TI - L-glutamic acid as a neurotransmitter in the CNS. PMID- 2900350 TI - The enteric nervous system--an overview. PMID- 2900351 TI - First results on mortality reduction in the UK Trial of Early Detection of Breast Cancer. UK Trial of Early Detection of Breast Cancer Group. AB - Between 1979 and 1981 the UK Trial of Early Detection of Breast Cancer enrolled women aged 45-64 living in eight locations in the United Kingdom. Annual screening by clinical examination of the breast, with mammography in alternate years, was provided over 7 years for 45,841 women; 63,636 were offered teaching in breast self-examination and were provided with a self-referral clinic; and 127,117, for whom no extra services were provided, form a comparison population. Over the 7 years from the start of the trial a reduction in the risk of dying from breast cancer in women offered screening relative to that in the comparison population was observed. The reduction was 14% (RR 0.86, 95% CI 0.69-1.08) when no allowance was made for underlying differences in breast cancer mortality between the populations, but rose to 20% (RR 0.80, 95% CI 0.64-1.01) when adjusted for differences in pretrial mortality rates. These differences fall short of statistical significance. No reduction in mortality was observed during the first 5 years but thereafter the gap widens. These results, though in themselves inconclusive, are consistent with the hypothesis that screening can achieve a worthwhile mortality reduction. No difference in mortality has so far been observed between women offered teaching in breast self-examination and the comparison population. PMID- 2900352 TI - Does prolonged breastfeeding adversely affect a child's nutritional status? AB - In 202 children who visited a children's hospital in the city of Accra, Ghana, breastfeeding beyond the age of 19 months was found to be associated with malnutrition. The effect of weaning on food intake was then studied in 15 breastfed malnourished children in a rural community. Before weaning (complete cessation of breast-feeding) protein and energy intakes of all the malnourished children were about half those of 5 normal children. 10 of the malnourished children were weaned, and their intakes rose to the levels of the normal children; the 5 who continued breastfeeding maintained their low intakes. These results indicate that prolonged breastfeeding can reduce total food intake and thus predispose to malnutrition. They also suggest that in Ghana and other developing countries the proper weaning age may be about 18 months. PMID- 2900353 TI - Identification of HIV-infected seronegative individuals by a direct diagnostic test based on hybridisation to amplified viral DNA. AB - There is a need for direct detection of the virus in people infected with human immunodeficiency virus (HIV), independently of a serological response. In this study, after enzymic amplification of a specific segment of the HIV genome, a simple slot-blot hybridisation procedure allowed unequivocal identification of HIV DNA in all seropositive subjects tested. More importantly, the hybridisation test allowed the detection of HIV DNA in several seronegative subjects from very high risk groups. This new direct approach towards the diagnosis of HIV infection, which can easily be carried out on a large scale, is therefore capable of identifying HIV-infected individuals before the development of antibodies. PMID- 2900355 TI - Gene studies in newborn males with Duchenne muscular dystrophy detected by neonatal screening. AB - 18,000 newborn males were screened for Duchenne muscular dystrophy (DMD) by creatine kinase (CK) analysis of filter paper blood spots between Jan 1, 1986, and Dec 31, 1987. 5 affected boys have been identified, and in 3 of 5 probands molecular deletions or duplications have been found. 3 of 5 mothers were judged highly likely to be carriers of DMD because of repeatedly raised CK levels, identified gene rearrangements, or both abnormalities. 1 mother has a very low probability of being a carrier and 1 is at an intermediate risk. The use of DNA analyses in new DMD probands identified by neonatal screening has allowed confirmation of the diagnosis and accurate assignment of carrier status in mothers and female relatives in over half the cases studied, and may help to reduce the population incidence of DMD by avoiding delay before clinical diagnosis. PMID- 2900354 TI - Participation of cell-mediated immunity in deposition of fibrin in glomerulonephritis. AB - Fibrin deposition is prominent in delayed-type hypersensitivity (DTH) reactions and is initiated by antigen-specific, T-lymphocyte-directed macrophage expression of human tissue factor (HTF). To examine the role of DTH in glomerular fibrin deposition, 10 fibrin-positive and 24 fibrin-negative biopsy specimens from patients with glomerulonephritis (GN) and samples from normal controls were studied with monoclonal antibodies against T cells, macrophages, and HTF. Fibrin positive sections showed intense glomerular staining for HTF and significantly more T cells and macrophages than fibrin-negative specimens. All the essential elements of DTH reactions can therefore be simultaneously demonstrated within glomeruli from patients with fibrin-related GN. These findings suggest a role for cell mediated immunity in GN. PMID- 2900356 TI - Dystrophin. PMID- 2900357 TI - Risking less treatment in cancer patients: lessons from germ-cell tumours. PMID- 2900358 TI - Complications of chronic volatile substance abuse. PMID- 2900359 TI - Routine vaginal examination at antenatal booking. PMID- 2900360 TI - Secretory IgA in recurrent urinary tract infections in childhood. PMID- 2900361 TI - Nodular hyperplasia and Cushing's syndrome. PMID- 2900362 TI - Diagnosis and treatment of presymptomatic Wilson's disease. AB - In ninety families with at least one proven case of Wilson's disease, seen over 32 years, all close relatives were examined and "presymptomatic" disease was diagnosed in 30. 11 had one or more abnormal physical signs when examined and 7 of these had Kayser Fleischer rings. In a further 10 patients the abnormalities of copper metabolism were so pronounced as to leave no doubt as to the diagnosis. 6 patients were not seen until they had been on treatment for 2 years or more; in some, much of the evidence on which the diagnosis was based is not available. In 3 patients there were only minor histological abnormalities in the liver and no increase in urinary copper but other indices of copper metabolism pointed to a diagnosis of Wilson's disease. 2 patients had transient neurological signs after starting treatment; otherwise, all but one (who died in an accident) have remained well for up to 26 years. PMID- 2900363 TI - Effect of antischistosomal chemotherapy on prevalence of Symmers' periportal fibrosis in Sudanese villages. AB - Almost all mortality caused by Schistosoma mansoni is secondary to Symmers' periportal fibrosis of the liver which can now be diagnosed by ultrasonography. This study assessed the usefulness of ultrasonography in measuring the effect of chemotherapy on the prevalence of Symmers' periportal fibrosis in Sudanese villagers. The prevalence of Symmers' fibrosis in 318 randomly selected patients from two villages not receiving systemic antischistosomal chemotherapy was compared with that in 168 patients from a village where antischistosomal chemotherapy had been systematically applied since 1979. The prevalence of Symmers' fibrosis was two to three times lower among treated villagers, with an eight-fold difference for villagers aged 10-20 years. PMID- 2900364 TI - Clinical effect of admission chest X-rays in Zimbabwe. AB - The independent effect of admission chest X-rays on clinical management of 432 consecutive patients admitted to general medical wards was prospectively evaluated. Diagnosis, investigations, and treatment were recorded on the basis of clinical findings alone. A chest X-ray was then taken and clinical effect measured by the resultant changes. Although 226 (53%) admission chest X-rays were abnormal, only 9% changed management. In patients with no clinical evidence of cardiorespiratory disease ("routine" X-rays, n = 214) the clinical effect was slight; management was changed in 5% and patient benefit resulted in 1.4%. Clinical effect was greatest in patients (n = 172) with definite signs of new cardiorespiratory illness (altered management 14%, patient benefit 6%) and patients (n = 34) with "possible" chest disease (altered management 9%, patient benefit 9%). Omission of admission chest X-rays in patients with no clinical evidence of chest disease, those with clinically stable, known chest disease, and those with isolated cardiomegaly or hyperinflated lungs would result in a 60% reduction in the number of admission chest X-rays. PMID- 2900365 TI - The arms race as a threat to health. PMID- 2900366 TI - Premorbid neuropathology in schizophrenia. PMID- 2900367 TI - Falling incidence of Reye's syndrome in Northern Ireland. PMID- 2900368 TI - Ultrasonic restoration of severely calcified aortic valve. PMID- 2900369 TI - Differentiating glomerular and non-glomerular haematuria. PMID- 2900370 TI - Anti-pre-S2 antibodies in clearance of hepatitis B virus. PMID- 2900371 TI - Age and obesity as risk factors in perioperative atrial fibrillation. PMID- 2900373 TI - Hypovitaminosis A of follicular duct as cause of acne vulgaris. PMID- 2900372 TI - Renal transplantation for dialysis arthropathy. PMID- 2900374 TI - Persistent virus infection and type 1 diabetes. PMID- 2900375 TI - Abnormalities of corpus callosum in patients with inherited metabolic diseases. PMID- 2900376 TI - Linkage heterogeneity in autosomal dominant polycystic kidney disease. PMID- 2900377 TI - HIV transmission to a blood donor. PMID- 2900378 TI - Severe group A streptococcal infection. PMID- 2900379 TI - HIV infection, breastfeeding, and human milk banking. PMID- 2900380 TI - Cat-scratch disease in patient with AIDS: atypical skin manifestation. PMID- 2900381 TI - No cat-scratch disease bacilli in sporadic epithelioid haemangiomas. PMID- 2900382 TI - Granulocytopenia due to fusidic acid. PMID- 2900383 TI - Irradiated neuroblastoma in childhood as potential risk factor for subsequent thyroid tumour. PMID- 2900384 TI - "Doctor" in Spain. PMID- 2900385 TI - Academic freedom. PMID- 2900386 TI - Facial injuries to restrained drivers caused by steering wheels. PMID- 2900387 TI - Excessive hours of work. PMID- 2900388 TI - Cyanide and fire victims. PMID- 2900389 TI - Gallstone lithotripsy. PMID- 2900390 TI - Central pontine myelinolysis not associated with rapid correction of hyponatraemia. PMID- 2900391 TI - Continuous arteriovenous haemodialysis in critically ill patients. PMID- 2900392 TI - Cyclosporin radioimmunoassay and cardiac transplantation. PMID- 2900393 TI - Bonney's blue. PMID- 2900394 TI - Legionnaires' disease following immersion in a river. PMID- 2900395 TI - Physical therapy in spastic diplegia. PMID- 2900396 TI - Hantavirus and Leptospira. PMID- 2900397 TI - Lysis in detection of intracellular organisms. PMID- 2900398 TI - Management of breast cancer in the elderly. PMID- 2900399 TI - General Medical Council advice on testing for HIV infection. PMID- 2900400 TI - AIDS in the UK. PMID- 2900401 TI - Safety, immunogenicity, and efficacy of recombinant live oral cholera vaccines, CVD 103 and CVD 103-HgR. AB - The genes encoding the A (toxic) subunit of cholera toxin were deleted from pathogenic Vibrio cholerae O1 strain 569B by recombinant techniques, leaving intact production of immunogenic, non-toxic B subunit. The resultant strain, CVD 103, evaluated for safety, immunogenicity, and efficacy as a live oral vaccine, was highly attenuated and elicited strong antibacterial and antitoxic immune responses; a single dose significantly protected volunteers against challenge with pathogenic V cholerae O1 of either serotype or biotype. A further derivative, CVD 103-HgR, which has an Hg++-resistance gene to differentiate it from wild-type vibrios, was also well-tolerated, immunogenic, and protective; moreover, faecal excretion of this derivative was significantly lower than that of CVD 103, which should minimise environmental spread of the vaccine. CVD 103 HgR is a candidate for expanded clinical trials in endemic areas. PMID- 2900403 TI - Does Sc1-70 modulate collagen production in systemic sclerosis? AB - Sc1-70, an autoantigen in systemic sclerosis, may accelerate collagen gene transcription by virtue of its activity as a topoisomerase I (topo I), a DNA template-modifying enzyme. A survey of sequences corresponding to all or part of the known topo I binding sequence AGAACTTAGAGAAAATTTAAA in four fibrillar collagen genes (three of them dermal) and sixteen non-collagen genes showed a striking preponderance of the tetramer 5'-CTTA-3', comprising the core of this binding sequence, at the exon-intron junctions of the fibrillar collagen genes (59% compared with 16% in the control group). In addition, a non-random clustering of three potential topo I binding sites was seen within 350 base-pairs of 5' flanking DNA in the dermal collagen gene alpha 2(I), and a fourth site occurred in the promoter region of the alpha 1(III) gene. The findings suggest that a selective vulnerability to the action of Sc1-70/topo I is built into the structure of the dermal collagen genes. PMID- 2900402 TI - Use of recombinant granulocyte-macrophage colony stimulating factor in the Brazil radiation accident. AB - 8 patients with bone marrow failure after a caesium-137 radiation accident were treated with recombinant human granulocyte-macrophage colony stimulating factor (rHuGM-CSF). The 7 who were evaluable had prompt increases in granulocytes and bone marrow cellularity. 2 patients died of radiation toxicity and haemorrhage and 2 of bacterial sepsis acquired before the start of rHuGM-CSF treatment. 4 patients survive, including 2 who were treated early and never became infected. This therapeutic approach to radiation-induced granulocytopenia may therefore be useful after radiation and nuclear accidents. PMID- 2900404 TI - Reduced felodipine bioavailability in patients taking anticonvulsants. AB - Felodipine is a dihydropyridine calcium antagonist, structurally related to nifedipine, which undergoes extensive first-pass hepatic metabolism and normally has an oral bioavailability of 15%. Felodipine disposition was studied in 10 patients who had microsomal enzyme induction due to chronic anticonvulsant therapy, and in 12 normal volunteers matched for age and sex. Plasma felodipine concentrations after a 5 mg oral dose were grossly reduced in the epileptic patients: the mean peak concentration was 1.6 (vs 8.9) nmol/l, and the area under the curve was only 2.0 (vs 30.0) nmol.h/l. The relative bioavailability of felodipine in the epileptic patients was thus only 6.6% of that in the normal subjects, and less than 1% of the oral dose was systemically available. Patients on anticonvulsant treatment will require substantially higher doses of felodipine to achieve plasma concentrations equivalent to those in non-induced subjects. PMID- 2900405 TI - Resection of haematogenous metastases. PMID- 2900406 TI - Chemotherapy of leprosy. PMID- 2900408 TI - Economics of the illicit drug market in the UK. PMID- 2900407 TI - Food and H2 blockade. PMID- 2900409 TI - Williams syndrome--the enigma continues. PMID- 2900411 TI - Gastro-oesophageal reflux and respiratory disorders in adults. PMID- 2900410 TI - Improved recovery and reduced postoperative stay after therapeutic suggestions during general anaesthesia. AB - The clinical value of therapeutic suggestions during general anaesthesia was assessed in a double-blind randomised placebo-controlled study. 39 unselected patients were allocated to suggestion (n = 19) or control (n = 20) groups who were played either recorded therapeutic suggestions or a blank tape, respectively, during hysterectomy. The patients in the suggestion group spent significantly less time in hospital after surgery, suffered from a significantly shorter period of pyrexia, and were generally rated by nurses as having made a better than expected recovery. Patients in the suggestion group, unlike those in the control group, guessed accurately that they had been played an instruction tape. PMID- 2900412 TI - Nuclear weapons test ban 1988. PMID- 2900413 TI - Air travel and thrombotic episodes: the economy class syndrome. PMID- 2900414 TI - Non-A, non-B hepatitis transmission by intravenous immunoglobulin. PMID- 2900415 TI - What causes diabetic renal failure? PMID- 2900416 TI - Are neonatal necropsies useful in developing countries? PMID- 2900417 TI - Epidemiology of listeriosis, England and Wales. PMID- 2900418 TI - Lack of effect of topical retinoic acid on sebum excretion rate in acne. PMID- 2900419 TI - Isotretinoin dose and teratogenicity. PMID- 2900420 TI - Dependence potential of benzodiazepines. PMID- 2900421 TI - Benzodiazepines and convulsions. PMID- 2900422 TI - Reversal of hepatic coma with flumazenil with improvement in visual evoked potentials. PMID- 2900423 TI - In-utero platelet transfusion for alloimmune thrombocytopenia. PMID- 2900424 TI - Guthrie cards for detection of point mutations in phenylketonuria. PMID- 2900425 TI - Bone-marrow transplantation for severe genetic anaemia. PMID- 2900426 TI - Triptorelin to prevent hysterectomy in patients with leiomyomas. PMID- 2900427 TI - Value of necropsy in AIDS. PMID- 2900428 TI - Zidovudine overdose. PMID- 2900429 TI - Simplified confirmatory HIV testing. PMID- 2900430 TI - No clinical signs 14 years after HIV-2 transmission via blood transfusion. PMID- 2900431 TI - Short-term buspirone treatment in disinhibition with dementia. PMID- 2900432 TI - Bacterial antigenic cross-reactions and haemolytic uraemic syndrome. PMID- 2900433 TI - Prazosin contraindicated in patients with narcolepsy. PMID- 2900434 TI - Anosmia. PMID- 2900435 TI - Anxiety and panic during magnetic resonance scans. PMID- 2900436 TI - Sleeping position and SIDS. PMID- 2900437 TI - Delayed seroconversion in Legionnaire's disease. PMID- 2900438 TI - Psoriasis and cyclosporin withdrawal. PMID- 2900440 TI - Fish oil and ischaemic heart disease in Greenland. PMID- 2900439 TI - Energy expenditure in children with cystic fibrosis. PMID- 2900441 TI - Salt and pregnancy-induced hypertension. PMID- 2900442 TI - Is Alzheimer's disease distinct from normal ageing? PMID- 2900443 TI - Hydrocortisone myopathy. PMID- 2900444 TI - Measurement of cardiac output. PMID- 2900445 TI - Renal failure during dissolution of gallstones by methylbutyl ether. PMID- 2900446 TI - Single photon emission computed tomography in diagnosis of herpes simplex encephalitis. PMID- 2900447 TI - Continuous intrapartum measurement of fetal oxygen saturation. PMID- 2900449 TI - The Khartoum floods and diarrhoeal diseases. PMID- 2900448 TI - Pulse oximetry and methaemoglobinaemia. PMID- 2900450 TI - Human herpesvirus-6 infection and disease. PMID- 2900451 TI - Chemotherapy and the circulating progenitor cell compartment. PMID- 2900452 TI - Coronary thrombolysis and myocardial salvage by tissue plasminogen activator. PMID- 2900453 TI - Wrong blood transfusion and Rhesus incompatibility. PMID- 2900454 TI - Bad professional relations and risks to patients. PMID- 2900455 TI - AIDS counselling. PMID- 2900456 TI - Parotid cysts and HIV infection. PMID- 2900457 TI - Evidence for involvement of the astrocytic benzodiazepine receptor in the mechanism of action of convulsant and anticonvulsant drugs. AB - The anticonvulsant drugs carbamazepine, phenobarbital, trimethadione, valproic acid and ethosuximide at pharmacologically relevant concentrations inhibit [3H]diazepam binding to astrocytes in primary cultures but have much less effect on a corresponding preparation of neurons. Phenytoin as well as pentobarbital (which is not used chronically as an anticonvulsant) are equipotent in the two cell types. The convulsants picrotoxinin and pentylenetetrazol, the convulsant benzodiazepine RO 5-3663 and the two convulsant barbiturates DMBB and CHEB similarly inhibit diazepam binding to astrocytes but have little effect on neurons. On the basis of these findings it is suggested that these convulsants and anticonvulsants owe at least part of their effect to an interaction with the astrocytic benzodiazepine receptor, perhaps by interference with a calcium channel. PMID- 2900458 TI - Dynorphin A [1-17] induces "reward" in rats in the place conditioning paradigm. AB - Intracerebroventricular (i.c.v.) administration of dynorphin A [1-17] induced significant place preference conditioning in male, Sprague-Dawley rats. Place preferences were induced by 2.3 and 3.5 nmole, but not 1.2 nmole of dynorphin A. Co-administration of naloxone, 27.5 nmole but not 5.5 nmole, antagonized the reward response induced by 2.3 nmole of dynorphin A. Leu-enkephalin, 5 or 25 nmole, and dynorphin A [2-17], 2.3 or 3.5 nmole, had no effect in the place conditioning paradigm. PMID- 2900459 TI - B-HT 920 stimulates postsynaptic D2 dopamine receptors in the normal rat: electrophysiological and behavioral evidence. AB - The putative autoreceptor-selective dopamine (DA) agonist B-HT 920 was tested using electrophysiological and behavioral models thought to reflect actions at postsynaptic D2 DA receptors. Direct iontophoretic application of B-HT 920 onto nucleus accumbens neurons caused a current-dependent inhibition of firing which could be attenuated by pretreatment with alpha-methyl-p-tyrosine (to deplete DA) and reinstated (enabled) by concurrent administration of the selective D1 DA receptor agonist SKF 38393. These findings suggest that, like other selective D2 DA receptor agonists, the postsynaptic effects of B-HT 920 require concurrent stimulation of D1 DA receptors. Behavioral indices of postsynaptic D2 DA receptor stimulation (stereotyped sniffing and rearing) were also evident following combined treatment with B-HT 920 and SKF 38393. Moreover, similar "low-level" stereotyped behaviors were also observed when B-HT 920 was administered alone following pretreatment with the alpha-2 adrenoceptor antagonists idazoxane and piperoxane, suggesting that alpha-2 agonist actions of B-HT 920, in some way, mask the expression of D2 receptor-mediated stereotyped responses. When B-HT 920 was combined with SKF 38393 following pretreatment with idazoxane, both the intensity and form (continual licking and gnawing) of stereotyped behavior was enhanced. Taken together, these electrophysiological and behavioral findings indicate that B-HT 920 possesses the properties of a selective D2 DA receptor agonist and cannot be considered as a DA autoreceptor-selective compound. PMID- 2900460 TI - Regulation of pyrC expression in Salmonella typhimurium: identification of a regulatory region. AB - Deletion analysis of a plasmid carrying the entire pyrC gene of Salmonella typhimurium served to localize the regulatory region within a 120 base pair DNA fragment comprising the promoter-leader region and the first 10 codons of pyrC. A region of dyad symmetry is present in the leader DNA and may result in the formation of a stable hairpin in the transcript with part of the Shine-Dalgarno sequence included in the stem. Four independently-isolated regulatory mutants, overexpressing pyrC, were found to have point mutations within the symmetry region and, significantly, the mutations occurred in sequences pertaining to either side of the stem of the putative hairpin of the transcript. All four mutations would decrease the stability of the hairpin, suggesting that pyrC expression is controlled at the level of translation. Additional evidence for translational control was provided by the finding that synthesis of galactokinase mediated from a pyrC-galK transcriptional fusion is not regulated by pyrimidines. The importance of the symmetry region in the leader was further emphasized by showing that pyrC expression is strongly affected when this region is deleted, inverted, or structured as a tandem duplication. PMID- 2900461 TI - Genes that modify expression of major urinary proteins in mice. AB - A survey of major urinary proteins (MUPs) from eight BALB/c mouse substrains by isoelectric focusing identified a common pattern with about 10 protein bands in males. One substrain, BALB/cJPt, differed in that it expressed two variant MUP patterns, designated 4.1lo and null. To find the chromosomal location of the gene which determines the 4.1lo phenotype, BALB/cJPt-MUP-4.1lo was crossed with a wild derived Mus musculus domesticus inbred strain (CLA) that expresses the common BALB/c MUP pattern. The F1 phenotype revealed that the gene(s) controlling the MUP-4.1lo trait was recessive. A restriction fragment polymorphism between these strains found with a MUP cDNA probe allowed us to establish that a gene determining the MUP-4.1lo trait was not linked to the MUP structural genes on chromosome 4. Assays for other chromosomal marker loci revealed that a gene determining the MUP-4.1lo trait, designated Mupm-1, was closely linked to Myc-1 on chromosome 15. To determine the genetic basis of the null trait, BALB/cJPt-MUP null mice were crossed with BALB/cJPt-MUP-4.1lo mice. A MUP restriction fragment polymorphism between these two lines was tightly linked to a gene or genes involved in determining the MUP-null phenotype. The two variant MUP phenotypes in BALB/cJ mice are determined by separate genes, one of which is located on chromosome 4 and the other on chromosome 15. The chromosomal location of Mupm-1 suggests that it produces a trans-acting factor which regulates MUP expression. PMID- 2900462 TI - [Isolation and characteristics of the bacteriophage from the vaccine strain Tohama phase I]. AB - Some properties of bacteriophage phi T isolated from the vaccine strain Bordetella pertussis Tohama phase I and propagated in Bordetella parapertussis 504 cells are presented. Phage phi T belongs to the IV group in accordance with Tikhonenko classification. The diameter of head and length of noncontractile tail sheath are 49.5 +/- 0.5 and 145 +/- 7 nm, respectively. Diameter of the tail sheath is 3.2 +/- 0.6 nm. Molecular mass of the phage DNA is 37 +/- 3 kb. Population of phi T phage is polymorphous and consists of particles the genomes or which vary from each other by the "insert" located 6.8 +/- 0.6 kb from the end of molecule. The blot hybridization has demonstrated that the bacteriophage genome is not inserted into the chromosome of the lysogenic strain. Autonomous location of the phage genome in the host cell is suggested. The temperature and hydrogen ions concentration effects on bacteriophage phi T stability were studied. The conditions for phage suspension storage are described. PMID- 2900463 TI - Report and recommendations of the San Antonio Conference on Diabetic Neuropathy. American Diabetes Association. PMID- 2900464 TI - Role of glucocorticoids in increased muscle glutamine production in starvation. AB - The influence of glucocorticoids on muscle glutamine production in starvation was studied by using cortisol-treated or non-cortisol-treated, starved, adrenalectomized rats. Administration of cortisol at physiological doses in vivo (1 mg/100 g body weight) to fasted, adrenalectomized rats increased the muscle ratio of glutamine/glutamate and the activity of glutamine synthetase after only 6 hours. Prior treatment of fasted, adrenalectomized animals with actinomycin D or proflavine abolished these increases by cortisol. Therefore, cortisol induces muscle glutamine synthetase, and this induction can be detected by changes in the fresh-muscle ratio of glutamine/glutamate. Using this ratio as a qualitative indicator of muscle glutamine synthesis, the role of glucocorticoids in modifying muscle glutamine production in starvation was studied. In fresh-frozen soleus, extensor digitorum longus, and diaphragm muscle, starvation led to greater ratios of glutamine/glutamate and higher levels of tyrosine, which are indicative of enhanced muscle protein turnover. These effects were not apparent in starved, adrenalectomized animals but were restored, at least partially, by administering a physiological dose of cortisol. Therefore, glucocorticoids seem essential for promoting muscle glutamine production in starvation probably by inducing the activity of glutamine synthetase. PMID- 2900465 TI - Seroprevalence of human T-cell lymphotropic virus type 1 among homosexual men in the United States. PMID- 2900466 TI - The discriminative stimulus properties of midazolam in pigeons. PMID- 2900467 TI - Precipitation of spinally mediated withdrawal signs by intrathecal administration of naloxone and the mu-receptor antagonist CTP in morphine-dependent mice. AB - We evaluated the ability of naloxone and the mu receptor antagonist CTP (D-Phe Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2) to precipitate withdrawal in morphine dependent mice after intrathecal (i.t.) administration. The withdrawal syndromes elicited by naloxone and CTP given i.t. were compared to those of CTP or naloxone injected intracerebroventricularly (i.c.v.). When given i.t. or i.c.v., naloxone produced the classical syndrome of events including jumping, wet dog shakes, urination, defecation followed by diarrhea, and weight loss. There was no significant difference in the potency or efficacy of naloxone when it was given i.t. or i.c.v. The profile of withdrawal effects produced by i.t. CTP resembled that caused by i.c.v. CTP; both were different from that of naloxone. The withdrawal signs seen following both i.t. or i.c.v. CTP included wet dog shakes and defecation. Mice treated with i.t. CTP lost significantly less body weight than those treated with i.c.v. CTP. In addition, i.t. and i.c.v. CTP did not stimulate jumping behaviors or diarrhea. In contrast, while i.c.v. CTP resulted in increased incidence of urination, CTP given i.t. did not. These finding indicate that naloxone given spinally acts on mu receptors to precipitate wet dog shaking and defecation, but acts on other non-mu opioid receptors (i.e. delta and/or kappa) to cause jumping, urination, diarrhea and weight loss. The differential effects of CTP given i.c.v. or i.t. suggest that supraspinal mu receptors are more involved in gastrointestinal and urinary bladder function during dependence/withdrawal than their spinal counterparts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900468 TI - Biological evaluation of compounds for their physical dependence potential and abuse liability. XI. Drug testing program of the Committee on Problems of Drug Dependence, Inc. (1987). PMID- 2900469 TI - Increased pH and tumorigenicity of fibroblasts expressing a yeast proton pump. AB - A common early response of eukaryotic cells to stimuli which activate their proliferation is an increase in intracellular pH (ref. 1). In animal cells this is caused by the activation of an Na+/H+ exchange system; in fungi and plants an H+-pumping ATPase is involved. The critical question is whether this intracellular alkalinization is merely coincident with the activation of cell proliferation or whether it is a regulatory signal. To increase intracellular pH bypassing the usual physiological stimuli (growth factors, hormones etc.) alkaline media or ammonia have been used in the past. Both approaches suffer from long-term toxicity effects and cannot be used in tumorigenic assays with whole organisms. We introduce here a more specific approach which involves expressing the gene for the yeast plasma membrane H+-ATPase in fibroblasts. The resulting cells have an elevated intracellular pH and acquire tumorigenic properties, suggesting that the yeast ATPase gene behaves as an oncogene in mammalian cells. These experiments support a crucial role of intracellular pH in the growth control of animal cells. PMID- 2900470 TI - Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB. AB - A nuclear protein, CREB, has been isolated from rat brain and shown to stimulate transcription of the cyclic AMP-responsive gene somatostatin as a dimer. Biochemical analysis suggests that dimerization and transcriptional efficacy of CREB protein in vitro are regulated by phosphorylation. These findings demonstrate that cellular signals can modulate gene expression by regulating the covalent modification of pre-existing nuclear factors. PMID- 2900471 TI - Prevention of guanine nucleotide-induced reductions in muscarinic agonist binding to rabbit ileal submucosal membranes by lidamidine and tetracaine. AB - The effects of low concentrations (less than = 1 microM) of the anti-diarrhoeal drug lidamidine and sub-anaesthetic concentrations (less than = 1 microM) of tetracaine on the binding of the muscarinic antagonist [3H]N-methylscopolamine ([3H]NMS) and the high affinity muscarinic agonist, [3H]oxotremorine-M ([3H]oxo M) to broken cell preparations of rabbit ileal submucosal membranes were investigated. High affinity [3H]NMS binding (KD = 0.79 +/- 0.05 nM, Bmax = 1.75 +/- 0.13 pmoles.mg-1) was unaffected by either lidamidine or tetracaine. Inhibition of NMS binding by the muscarinic agonist carbachol was reduced by the nonhydrolyzable analogue of GTP, GppNHp. This effect of GppNHp was partially prevented by lidamidine. Analysis of equilibrium binding of the muscarinic agonist [3H]oxotremorine-M revealed that the binding of oxotremorine-M could be best described by the presence of the least two populations of sites with affinities of 0.9 +/- 0.2 and 27.7 +/- 0.9 nM respectively. High affinity [3H]oxotremorine-M binding was markedly reduced by GppNHp, GDP beta S and fluoride (5 mM). Neither lidamidine, nor tetracaine had any effect on the binding of oxotremorine-M when added alone. However, lidamidine and tetracaine prevented GppNHp, GDP beta S and fluoride-induced reductions in oxotremorine-M binding. The present findings are consistent with an allosteric interaction between lidamidine or tetracaine and GppNHp-induced reductions in oxotremorine-M binding to submucosal muscarinic receptors. These effects are discussed in relation to the observed action of lidamidine in potentiating presynaptic inhibition of acetylcholine release by muscarinic agonists. PMID- 2900472 TI - Comparison of the effects of haloperidol, remoxipride and raclopride on "pre"- and postsynaptic dopamine receptors in the rat brain. AB - The ability of the dopamine receptor antagonists haloperidol, raclopride and remoxipride to prevent the B-HT 920-induced decrease in striatal and limbic L DOPA accumulation in gamma-butyrolactone (GBL)- and NSD 1015-treated rats (termed 'GBL-reversal') was used to define the effects of these compounds on "presynaptic" dopamine receptors. The doses of the dopamine antagonists producing antagonism of GBL-reversal were in each case roughly similar to the doses required to increase dopamine turnover in striatal and limbic areas. The potencies of haloperidol, raclopride and remoxipride in the GBL model were compared with their potencies in behavioural models for postsynaptic dopamine receptors. Haloperidol produced antagonism of GBL-reversal over a similar dose range to that required for antagonism of apomorphine-induced hyperactivity and stereotypy syndromes. Raclopride was effective in the order of potency: antagonism of apomorphine-induced hyperactivity greater than antagonism of GBL reversal greater than antagonism of apomorphine-induced stereotypy. For remoxipride, the dose-response curve for antagonism of GBL-reversal was superimposable over that for antagonism of apomorphine-induced stereotypies, with an ED50 value about 12 times higher than that for antagonism of apomorphine induced hyperactivity. Thus, the relative potencies of dopamine receptor antagonists at "pre-" and postsynaptic dopamine receptors vary considerably from compound to compound. PMID- 2900473 TI - Presynaptic beta 2-adrenoceptors on the sympathetic nerve fibres of the human saphenous vein: no evidence for involvement in adrenaline-mediated positive feedback loop regulating noradrenergic transmission. AB - Spirally cut strips of human saphenous veins preincubated with 3H-noradrenaline were superfused in the presence of corticosterone and, unless stated otherwise, of cocaine or desipramine. Tritium overflow was stimulated electrically (2 Hz). Adrenaline (in the presence of rauwolscine), isoprenaline and the preferential beta 2-adrenoceptor agonist procaterol concentration-dependently increased the electrically evoked tritium overflow. Prenalterol, a beta-adrenoceptor agonist with moderate preference for beta 1-adrenoceptors, was ineffective. The concentration-response curve of isoprenaline was shifted to the right by the nonselective beta-adrenoceptor antagonist propranolol and by the preferential beta 2-adrenoceptor antagonist ICI 118,551, but was not affected by the beta 1 selective antagonist atenolol. In experiments on strips preexposed to adrenaline 10 nmol/l (i.e. a concentration higher than that which normally occurs in vivo) for 32 min in the absence of cocaine or desipramine, the electrically evoked 3H overflow was not affected 12 and 44 min after withdrawal of adrenaline, irrespective of whether propranolol was absent or present in the superfusion fluid. In veins incubated with 3H-adrenaline, a considerable amount of the radioactivity was accumulated. During subsequent superfusion with 3H-adrenaline free solution, electrical stimulation induced tritium overflow in a tetrodotoxin sensitive manner. Propranolol failed to modify the evoked tritium overflow. It is concluded that the sympathetic nerve fibres of the human saphenous vein are endowed with facilitatory presynaptic beta 2-adrenoceptors. These receptors do not seem to play a substantial role in a local adrenaline (previously taken up) mediated positive feedback loop regulating noradrenergic transmission, at least under the present in vitro conditions. PMID- 2900474 TI - Effect of alpha 1-adrenoceptor stimulation with methoxamine and phenylephrine on spontaneously beating rabbit sino-atrial node cells. AB - Effects of methoxamine and phenylephrine on the action potential and the membrane currents in spontaneously beating rabbit sino-atrial node cells were examined by means of a two-microelectrode voltage-clamp technique. Both methoxamine and phenylephrine (10(-4) mol/l) prolonged the cycle length (CL) and the action potential duration (APD), significantly. At concentrations higher than 3 x 10(-4) mol/l, phenylephrine increased the maximum rate of rise of action potential (Vmax) but methoxamine reduced it. Both agents depolarized the maximum diastolic potential (MDP). These changes in the action potential parameters occurred in a concentration-dependent manner. In the presence of phentolamine (10(-5) mol/l), methoxamine (3 x 10(-4) mol/l) did not modify the action potential parameters. Also, phenylephrine did not affect them during exposure to phentolamine (10(-5) mol/l) and pindolol (10(-7) mol/l). In voltage-clamp experiments, at 10(-3) mol/l both methoxamine and phenylephrine slightly increased the slow inward current (Isi), but decreased the time-dependent outward current (Ik). The steady-state activation variable of Ik (p infinity) was unaffected by these agents. The hyperpolarization-activated current (Ih) was suppressed in the presence of methoxamine, but enhanced in the presence of phenylephrine. An additional application of pindolol (10(-7) mol/l) during exposure to phenylephrine (10(-3) mol/l) depressed the action potential amplitude (APA) and Vmax, and prolonged CL slightly. Under the same condition, all the membrane currents (Isi, Ik and Ih) were decreased. In addition, the time courses of decay for Isi were not modified in the absence and the presence of phenylephrine (10(-3) mol/l) and phenylephrine plus pindolol (10(-7) mol/l).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900475 TI - Inhibition of vascular smooth muscle relaxation by LY83583. AB - The ability of LY83583 to antagonize vascular smooth muscle relaxation elicited by a number of vasodilators was examined in rings of rat aorta. LY83583 (0.3-10 microM) inhibited relaxant responses to acetylcholine, calimycin (A23187), adenosine triphosphate (ATP) and sodium nitroprusside, whereas responses to atriopeptin III an activator of particulate guanylate cyclase, and papaverine were unaffected. For acetylcholine and calimycin the major effect of LY83583 (0.3 10 microM) was to reduce the maximal response without appreciably altering the EC50 values whereas for ATP the EC50 values were markedly increased by low concentrations of LY83583 (0.3-1 microM) with depression of maximal responses occurring at higher concentrations (10 microM) of the antagonist. In contrast LY83583 produced nonparallel rightward shifts of the curve for sodium nitroprusside without altering the maximal response. In addition, LY83583 (10 microM) reduced basal levels of cyclic GMP and prevented acetylcholine and sodium nitroprusside-induced elevations of cyclic GMP, in parallel with reductions in the relaxant responses. In the presence of LY83583 (10 microM) higher concentrations of sodium nitroprusside restored both the relaxant response and the elevation of cyclic GMP. The results of this study show that LY83583 antagonises only those vasodilators which are thought to act via stimulation of soluble guanylate cyclase. The nonsurmountable inhibition of relaxation to acetylcholine, calimycin and ATP probably reflects a limited maximal capacity of the endothelium to release EDRF in response to these agents. PMID- 2900476 TI - Critical thinking and fatigue: how do nurses on 8- & 12-hour shifts compare? PMID- 2900477 TI - [New aspects of Huntington disease. The neurotoxin hypothesis, genetic diagnosis and psychological sequelae]. PMID- 2900478 TI - [Metachromatic leukodystrophy. Results of laboratory chemical, neurophysiologic, histologic and imaging procedures within the scope of a family study]. AB - Examining the members of a family the validity of chemical analysis, neurophysiology and neuroimaging for the diagnosis of metachromatic leukodystrophy (MLD) is discussed. As the arylsulfatase A is not decreased in all cases, the neuroimaging (cranial computerized tomography--at a less extend magnetic resonance imaging) gains a particular diagnostic significance. But neither for neuroimaging nor for neurophysiological findings the results are specific. The histological findings have to back up the diagnosis. PMID- 2900479 TI - Spontaneous release of endogenous aspartate and glutamate from rat striatal slices is increased following destruction of local neurons by ibotenic acid. AB - We sought to determine in rat striatum whether the release of neurotransmitter amino acids aspartate (Asp), glutamate (Glu) and gamma-aminobutyric acid (GABA) were affected by local neurons. To do so, unilateral microinjections of ibotenic acid, and excitotoxin that destroys local neurons without affecting fibers of passage, were made into the striatum. Release of endogenous amino acids from lesioned and intact striatal slices were measured by HPLC one week later. The effectiveness and specificity of the lesion were confirmed by measuring the enzyme activity associated with extrinsic dopamine neurons (tyrosine hydroxylase; 111 +/- 14%), intrinsic GABA neurons (glutamic acid decarboxylase; 19 +/- 7%) and intrinsic acetylcholine neurons (choline acetyltranferase; 37 +/- 10%). Destruction of local striatal neurons markedly attenuated the release of GABA (41 +/- 12% of control) elicited by depolarization with K+ (35 mM), but did not significantly reduced the K+-evoked release of Asp (80 +/- 17%) and Glu (92 +/- 8%). However, spontaneous release of Asp and Glu was significantly greater than that observed in unlesioned tissue (159 +/- 18% and 209 +/- 27%, respectively), while the spontaneous release of GABA was not significantly reduced (75 +/- 43%). Although release of the neurotransmitter amino acids Asp, Glu and GABA were affected by the lesion, the release of the non-neurotransmitter amino acid tyrosine was unaffected. These data are consistent with the hypotheses that: 1) the predominant source of releasable stores of endogenous Asp and Glu in the striatum arises from extinsic neurons, and 2) that the spontaneous release of Asp and Glu from axon terminals in the striatum may be regulated, at least in part, by local inhibitory neurons. PMID- 2900480 TI - Postmortem stability of somatostatin in brain tissue. AB - The stability of somatostatin (SS) in brain tissue was studied in human material obtained post-mortem and in the rat. In both human and rat brain, loss of SS was found to occur in tissue frozen to -70 degrees C. In the rat, this loss varied from 26 to 70 percent depending on the type of tissue processing used. These data suggest that, for the study of SS in post-mortem brain, use of frozen material should be avoided. PMID- 2900481 TI - Effects of neuroleptics on glutaminase from rat synaptosomes. AB - Phosphate-activated glutaminase was isolated from synaptosomes from three areas of rat brain. Glutamine utilization phosphate activation and inhibition by glutamate or ammonia were assessed in the absence or presence of haloperidol, chlorpromazine, or clozapine. All three drugs (at 1 micromolar concentration) elevated the Km for glutamine using preparations from the amygdala, hippocampus, or striatum. They interfered with phosphate activation only in the amygdala preparation. No drug affected end-product inhibition. The data suggest that neuroleptics may depress the release of glutamic acid from synaptosomes by interfering with the activation of glutaminase by phosphate. PMID- 2900483 TI - Alprazolam compared to clobazam and placebo in anxious outpatients. AB - In this double-blind study we compared alprazolam, clobazam, and placebo for the treatment of outpatients suffering from generalized anxiety disorder. At the end of the treatment, the three groups were significantly improved without showing differences among them. However, both active-drug groups were much improved at the end of week 1 in contrast to the placebo group. We were unable to find any difference on efficacy evaluations between alprazolam and clobazam, but alprazolam reached a consistently better outcome on some ratings compared to placebo. Although benzodiazepines share many common properties, it is necessary to identify selected groups of patients that can be helped by specific compounds or even placebo. PMID- 2900482 TI - Certain neuroleptics reduce bone mineralization in schizophrenic patients. AB - A significant increase of urinary Ca and hydroxyproline levels and a decrease of urinary alkaline phosphatase activity were found in 12 schizophrenic patients receiving certain neuroleptic drugs. In these patients, the levels of active metabolites of vitamin D3 were decreased, while the levels of midmolecule parathyroid hormone were within the normal range, except for 2 cases. These results suggest that certain neuroleptics induce the increased urinary Ca excretion through suppression of active vitamin D3 formation and that chronic treatment with certain neuroleptics may induce abnormal bone mineralization. PMID- 2900484 TI - Long-term replicability of EEG spectra and auditory evoked potentials in schizophrenic and normal subjects. AB - The spectral characteristics and average, auditory evoked potentials (AEPs) were determined from EEGs repeatedly recorded over a span of several years. Data from a vertex lead is presented for 4 chronic schizophrenic patients and 5 normal subjects. Measurements were made under identical conditions. For each subject characteristic spectra and AEPs were exhibited despite the passage of time. Patients had recordings performed both on and off antipsychotic medication. While receiving antipsychotic medication the patients' EEG spectra showed an increase in alpha activity. Less consistently there was a decrease in delta or an increase in beta activity; theta activity was unchanged. These latter effects are different from those generally reported for an acute antipsychotic dose and may be more representative of antipsychotic effects (which occur after days or weeks of treatment). Psychopathology tended to be inversely related to alpha power, the magnitude of the AEP N100, and medication. PMID- 2900485 TI - Adult T-cell leukemia/lymphoma in pregnancy. AB - Adult T-cell leukemia/lymphoma, a lymphocytic leukemia caused by human T-cell lymphoma virus-I (HTLV-I), is prevalent in southwestern Japan. A Japanese woman with adult T-cell leukemia/lymphoma in the third trimester of pregnancy was delivered of an infant by cesarean section. She did not breast-feed the child, who has remained free from HTLV-I infection. PMID- 2900486 TI - Medical management of pheochromocytoma in pregnancy. AB - A pregnant patient presented with a history of diagnosed pheochromocytoma. Despite excision of the extra-adrenal tumor before pregnancy, the patient's urine catecholamine levels and blood pressure remained elevated. Subsequent attempts at localizing the tumor, including repeat laparotomy, were unsuccessful. The patient was medically managed with alpha blockade from the first trimester and was delivered by cesarean section after demonstration of fetal lung maturity at 35 weeks' gestation. She represents one of the few reported cases of successful medical management of pheochromocytoma throughout the entire course of a pregnancy. PMID- 2900487 TI - The pathology of intrauterine thyrotoxicosis: two case reports. AB - The autopsy findings are described in two infants of hyperthyroid mothers in whom the clinical symptomatology, laboratory data, and autopsy findings strongly suggested intrauterine thyrotoxicosis secondary to transplacental thyroid stimulating immunoglobulin. Documented intrauterine thyrotoxicosis is extremely rare, and we believe these to be the first detailed pathologic descriptions of the entity. Autopsy findings included slim habitus, massive thyromegaly, hypertrophic cardiomegaly, congestive visceromegaly, pulmonary hypertension, adenopathy, and prominent amniotic fluid aspiration. Both cases illustrate the positive contribution that a carefully performed autopsy, even in the severely macerated stillborn, can make toward better understanding of intrauterine disease. PMID- 2900488 TI - [In vitro activity of roxithromycin against hospital bacteria and the concordance curve]. AB - This study was set up to establish the regression curve for roxithromycin inhibition zone diameters (disks 15 micrograms) and MIC to create a strain distribution plot, in order to allow accurate interpretation of the disk diffusion method for testing susceptibility to roxithromycin. 373 bacterial strains were studied in three university hospital. Roxithromycin was active against erythromycin sensitive Staphylococcus aureus and coagulase negative Staphylococci at concentrations of 0.06 to 4 micrograms/ml (mode 0.5). Erythromycin resistant strains were also resistant to roxithromycin. Enterococci could be divided into two populations, one resistant (MIC greater than 128 micrograms/ml) and the other with MIC of 0.5 to 32 (mode 1-2). This was also the case for Streptococci and Pneumococci with MIC lower for susceptible strains (mode 0.06-0.12). Roxithromycin was active on Haemophilus at concentrations of 0.12 to 32 micrograms/ml; MIC for beta-lactamase producing strains were comparable to those of strains not producing. MIC for Gonococci were low (less than 0.008 to 0.12), except for three strains. They were higher for Meningococci (0.03 to 32) with a majority of strains inhibited by 0.5 to 4 micrograms/ml. MIC were 4 for Clostridium perfringens; Bacteroides fragilis strains were inhibited by 0.5 to 2 micrograms/ml. The correlation coefficient for regression curve was 0.79; for critical concentrations less than or equal to 1 and greater than 4 micrograms/ml, critical diameters are greater than or equal to 22 and less than 17 mm. PMID- 2900489 TI - [Demonstration of seasonal variations of circadian rhythm in gentamicin-induced chrono-nephrotoxicity in rats]. AB - The present study investigates the chronobiological approach of the gentamicin induced nephrotoxicity in rats treated with a single sublethal dose administered at different times of day and season of year. The nephrotoxicity is appreciated by gamma-glutamyl-transferase and alanine-amino-peptidase, two enzymes of the brush border cells and N-acetyl-beta-D-glucosaminidase, a lysosomal enzyme. These excretions peak out at 8 p.m. and reach a through at 8 a.m. for the experimentation in january-february. In contrast, for the experimentation in June July, we evidence gamma-glutamyl-transferase and alanine aminopeptidase excretion increased at 2 p.m. and decreased at 8 p.m. So, we evidence with gentamicin not only a circadian but also a seasonal susceptibility in rats. PMID- 2900490 TI - [Hyperammonemia in childhood. II. Enzymopathies not related to the urea cycle]. PMID- 2900491 TI - Chronic ipecac poisoning in infancy: a case report. PMID- 2900492 TI - Intentional ipecac poisoning: Munchausen syndrome by proxy. AB - The intentional poisoning of two children with ipecac by their mothers is described. Intractable vomiting and diarrhea were the initial symptoms in both patients. In addition, one patient had clinical and laboratory evidence of skeletal and cardiac myopathy. Both children were subjected to extensive and invasive diagnostic evaluations before the correct diagnosis of chronic ipecac poisoning was made. These cases illustrate the toxic effects of ipecac ingestion and serve to alert physicians to child abuse by ipecac poisoning. PMID- 2900493 TI - In defense of retaining ipecac syrup as an over-the-counter drug. PMID- 2900494 TI - Ascendancy of the 'black bottle'. PMID- 2900495 TI - Human estrogen receptor (ESR) gene locus: PssI dimorphism. PMID- 2900498 TI - A high frequency MspI RFLP at the human vitamin D binding protein (hDBP) locus. PMID- 2900496 TI - RFLP for Duchenne muscular dystrophy cDNA clone 44-1. PMID- 2900497 TI - Phage 8-10 identifies an RFLP on 11q23-qter [HGM9 no. D11S286]. PMID- 2900499 TI - RFLP for an EGF-receptor related gene associated with the melanoma oncogene locus of Xiphophorus maculatus. PMID- 2900500 TI - An anonymous DNA probe (LAMP 92) detects a Pvu II polymorphism on human chromosome 9 [D9S29]. PMID- 2900501 TI - RFLPs upstream of the low-density lipoprotein receptor (LDLR) gene. PMID- 2900502 TI - Human LDL receptor gene: HincII polymorphism detected by gene amplification. PMID- 2900503 TI - A Taq 1 polymorphism for the human platelet glycoprotein IIIa gene (GP3A). PMID- 2900504 TI - Human amyloid beta protein gene locus: HaeIII RFLP. PMID- 2900505 TI - [Autologous transplantation of hematopoietic stem cells]. PMID- 2900506 TI - [Gamma-glutamyltransferase activity in the plasma of patients with alcoholic and opiate abstinence syndromes]. PMID- 2900507 TI - Influence of age, strain, and beta-adrenergic agonist on insulin sensitivity in chicks as determined by an adaptation of the euglycemic clamp technique. AB - The euglycemic clamp technique has been widely used to examine changes in in vivo insulin sensitivity during physiological changes in mammals. The technique offers the advantage that the tissue uptake of glucose induced by a set dose of insulin is determined at the normal (steady state) circulating concentration of glucose (euglycemia). The euglycemic clamp technique has been modified to examine in vivo sensitivity to insulin in chickens. Insulin sensitivity is determined by the rate of infusion of exogenous glucose required to maintain euglycemia. Young (6 to 8 wk-old) male chickens (White Leghorn) are more sensitive to insulin than adult males of the same strain. There is, however, no difference in insulin sensitivity between young male chicks of broiler and White Leghorn strains. Chronic administration of beta-adrenergic agonist (L-640,033, donated by Merck, Sharp, and Dohme Research Laboratories, Rahway, NJ) in the diet, at levels of 0, .25, 1.0, and 4.0 ppm for 3 to 5 days also did not influence in vivo insulin sensitivity. PMID- 2900508 TI - Substrate specificity of duckling hepatic and renal D-amino acid oxidase. AB - The substrate specificity of duckling hepatic and renal D-amino acid oxidase (DAAO; D-amino acid: O2 oxidoreductase [deaminating], E.C. 1.4.3.3) was determined using a method based on the combination of coupled enzyme reactions and a colorimetric procedure. When activities were averaged across tissues, D proline was the most reactive substrate, followed by (in order) D-phenylalanine, D-alanine, D-methionine, D-leucine, D-isoleucine, D-valine, D-tryptophan, D arginine, and D-lysine. Compared with D-alanine, duckling DAAO had minimal or no reactivity with D-asparagine, D-glutamine, D-histidine, D-threonine, D-cysteine, glycine, or D-serine. These results were in general agreement with data from other vertebrate species. PMID- 2900509 TI - [Tropical spastic paraparesis related with HTLV1 in Guadeloupe]. PMID- 2900510 TI - Maxillofacial and dental injuries in contact team sports. PMID- 2900511 TI - Transdifferentiation of human neuroblastoma cells results in coordinate loss of neuronal and malignant properties. PMID- 2900512 TI - Differential expression of intermediate filaments and fibronectin in human neuroblastoma cells. PMID- 2900513 TI - Ewing's sarcoma is an undifferentiated neuroectodermal tumor. PMID- 2900514 TI - Double-blind randomized trial of the benzodiazepine derivative metaclazepam as compared with placebo treatment of outpatients with anxiety syndromes. AB - In a double-blind randomized study the therapeutic anxiolytic efficacy and the tolerance of metaclazepam were tested in comparison with placebo. The study was performed according to the model of the "Study Group - Psychotropic Drugs in Medical Practice" (Laakmann and Hippius, 1981; Laakmann et al., 1982). A total of 121 male and female patients aged between 18 and 50 years were treated either with placebo, or with 15 mg or with 30 mg metaclazepam/day for two weeks, during which period they were examined on Day 0, Day 7 and Day 14. The patients suffered from a neurotic anxiety syndrome. In the physician's rating metaclazepam showed a therapeutic effect significantly superior to that of placebo, both in the Clinical Global Impressions (CGI) and in the Hamilton Anxiety Scale (HAMA). This effect was already noticeable at the end of the first week. Similarly, a significantly superior anxiolytic activity of metaclazepam as compared with placebo was observed in the patients' ratings in the course of treatment. This was true for the Erlangen Anxiety Scale (EKSA) as well as for the Scale of Well being (Befindlichkeits-Skala [Bf-S]) and the List of Complaints (Beschwerden Liste [B-L]) by von Zerssen. No difference in efficacy could be found between the doses of 15 mg and 30 mg metaclazepam/day, neither in the physicians' nor in the patient's ratings. Compared with placebo, twice as many undesirable side effects were recorded with 15 mg metaclazepam and three times as many with 30 mg metaclazepam. This was clearly demonstrated by the significantly higher frequency of daytime fatigue after 30 mg metaclazepam.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900515 TI - The prevention and avoidance of genetic diseases. PMID- 2900516 TI - The importance of genetic disease and the need for prevention. AB - Until recently the effects of disease could only be reduced by prevention and treatment. It is now possible to interrupt development after fetal diagnosis. This prevents birth, but not the cause of the disease, and is usefully termed 'avoidance'. Genetic disorders are the consequence of mutational events in the past, including the remote and the immediate past, and prevention, in its true sense, can only be applied to preventing further mutations. This requires a knowledge both of the mechanism of mutation and of the mutagens to which populations and individuals are exposed, and the maintenance of public health requires the collection of data relevant to mutational disease. PMID- 2900517 TI - The human gene map. AB - Mapping started exactly 50 years ago when Bell & Haldane (Proc. R. Soc. Lond. 123, 119 (1937] measured the genetic distance between colour blindness and haemophilia. In their Discussion they wrote 'if...an equally close linkage were found between the genes determining blood group membership and that determining Huntington's chorea, we should be able, in many cases, to predict which children of an affected person would develop this disease, and to advise on the desirability or otherwise of their marriage'. Progress in this direction has proceeded through the discovery of autosomal linkages by family studies, and the assignment of genes to particular chromosomes by somatic-cell hybridization techniques. Recombinant DNA technology has been successfully used in both approaches, with the result that many chromosomes are now roughly mapped. In practice, the map can already be used for prenatal diagnosis of several diseases, and may provide 'take-off' points for some molecular approaches to poorly defined genes. More fundamentally, it is beginning to provide insights into the nature of the meiotic process and the organization of the genome. PMID- 2900518 TI - Progress in the molecular cytogenetics of man. AB - Recombinant DNA technology has contributed greatly to the precision of chromosome analysis in man. Breakpoints of chromosome deletions and rearrangements may be defined on a chromosome map whose landmarks are the loci of DNA sequences rather than Giemsa bands. Flow cytogenetics allows the extent of chromosome duplications and deletions to be measured more precisely than has hitherto been possible. DNA probes can reveal hidden translocations through the application of in situ hybridization, and may be used as markers to determine the parental origin of non disjunction. It is evident that a study of the pathology of human chromosomes now requires the combined skills of recombinant DNA and cytology. PMID- 2900519 TI - The role of cloned genes in the prevention of genetic disease. AB - The application of recombinant DNA technology to the study of human genetic disease promises to increase the scope for carrier detection and prenatal diagnosis. Here we summarize current experience with prenatal diagnosis of single gene disorders by DNA analysis and highlight some of the technical and organizational problems that remain to be solved. PMID- 2900520 TI - Progress towards cloning the cystic fibrosis gene. AB - Genetic linkage analysis with polymorphic DNA markers (restriction fragment length polymorphisms: RFLPS) has allowed the assignment of the cystic fibrosis (CF) locus to the long arm of chromosome 7, within the region of band q31. Two of these markers, MET and D7S8, are tightly linked to the disease locus. Although recent data suggest that they are located on opposite sides of CF, the two can be separated by as much as 5 centimorgans. To obtain a better description of the CF locus and, eventually, to identify the affected gene, additional DNA markers are required to connect MET and D7S8, physically. We have screened the flow-sorted chromosome-7-specific library and thus far isolated 28 new probes from the 7q31 region by DNA hybridization analysis that uses a series of somatic cell hybrids containing various portions of human chromosome 7. Together with the previously identified markers, MET, D7S8, D7S13 and D7S16, these new markers should provide a fine genetic and physical map for the chromosomal region surrounding CF. DNA segments can then be sequentially cloned by chromosome walking from points closest to the CF locus and examined for genes that are preferentially expressed in tissues known to be affected in the disease. PMID- 2900521 TI - The problem of Duchenne muscular dystrophy. AB - Duchenne muscular dystrophy (DMD) is a lethal X-linked muscular disorder. The biochemical defect remains unknown, but the gene responsible has been mapped to band Xp21. The gene has now been cloned in two laboratories solely from knowledge of its map location. L. M. Kunkel and his colleagues isolated genomic sequences (PERT 87) from within a large deletion causing DMD, whereas our group isolated genomic sequences (XJ) spanning the junction of an X-autosome translocation causing the disease. Chromosome walking by both groups has led to the isolation of over 400 kilobases of the PERT 87 and XJ region. Subclones of PERT 87 and XJ reveal restriction fragment length polymorphisms that segregate with the DMD gene in 95% of meioses, and fail to hybridize with DNA from about 8% of male patients. Selected subclones of PERT 87 and XJ contain exons that hybridize to muscle derived complementary DNA (cDNA) clones. The cDNA clones detect a large (16 kilobase) message. Analysis of deletions, mutations and translocations suggests a DMD gene of between two million and three million base pairs. The clones obtained so far are useful for attempts to generate antibody against the gene product and for carrier identification and prenatal diagnosis. PMID- 2900523 TI - Prospects for a complete molecular map of the human genome. AB - Linkage maps are limited by the number of recombinations that can be scored in human pedigrees to a resolution of ca. 1 centimorgan (relative distance between genes on a chromosome having a crossover value of 1%) which is estimated to be about 10 megabases. Molecular maps can be formed at any resolution down to the base sequence. To complement the linkage approach, the most useful molecular map would be one that helped to locate disease loci, by using restriction fragment length polymorphisms (RFLPS) and accurate localization of recombinations, and which then helped to find candidate genes in this region, by providing the positions of coding sequences. This paper discusses the appropriate form and scale of such a map, how it can be produced with methods now available, and the most efficient strategy for building the map, based on present knowledge of the organization of the human genome. PMID- 2900522 TI - Huntington's disease: prediction and prevention. AB - The identification of a DNA restriction fragment length polymorphism closely linked to Huntington's disease on the short arm of chromosome 4 has for the first time allowed presymptomatic prediction to be undertaken in first-degree relatives at risk. The late and variable onset of this dominantly inherited disorder makes such prediction a powerful and potentially valuable aid in genetic counselling, but in the absence of effective therapy there are serious ethical reservations concerning such a predictive test. The new developments have stimulated an active and informative debate among professionals and family members on whether and how predictive tests should be used. Guidelines have emerged which should be useful not only for Huntington's disease, but for other serious late-onset neurogenetic disorders. Meanwhile, studies in Wales and elsewhere have not only confirmed the original linkage but have excluded multi-locus heterogeneity as a significant problem. Genetic prediction for the individual at risk remains critically dependent on a suitable family structure, present in only a minority of families in Wales. A more feasible alternative for most families is prenatal exclusion, which can allow risk prediction for a pregnancy without altering the situation for the person at risk. This approach has already been applied in Wales; the experience gained will be useful in full prediction, which is currently being introduced. PMID- 2900524 TI - Prevention and avoidance of congenital malformations. AB - Many congenital abnormalities do not have either a Mendelian pattern of inheritance or an identifiable chromosome abnormality and are described as 'multifactorial' as it is assumed they are determined by several genes, each with added effects and modified to a greater or lesser extent by environmental factors. They include spina bifida and anencephaly, cleft lip or cleft palate or both, congenital heart defect and congenital dislocation of the hip, and they constitute a major community health problem. Developments in genetics, biochemistry and cytogenetics have presented new approaches to the prevention and avoidance of congenital abnormalities. The approaches available for the avoidance of congenital malformations include the avoidance of harmful environmental factors, the screening of the newborn and early treatment, genetic counselling and antenatal monitoring with selective termination. The prevention of neural tube defects in 'high risk' mothers can be achieved by periconceptional vitamin supplementation. In Northern Ireland, of 438 fully supplemented women, only 4 (0.98%) infants or fetuses among 407 infants and fetuses examined had a neural tube defect, whereas of 356 unsupplemented women, 16 (4.7%) infants or fetuses among 337 infants or fetuses examined had a neural-tube defect. PMID- 2900525 TI - The incidence of Down's syndrome and progress towards its reduction. AB - Down's syndrome is the most common autosomal aberration and single cause of mental retardation in man. There is a close relation between advanced maternal age and Down's syndrome. The limitation of family size has made a considerable impact on the incidence of Down's syndrome. In Denmark in the 1950s, 50% of Down's syndrome cases were born to mothers over the age of 35. The percentage went down to 25% in the 1970s and was reduced by prenatal diagnosis to 8% in the 1980s. For the period 1980-85 we followed the birth prevalence closely for different maternal age groups. The birth prevalence was lowered for the age group over 35, but there was a steady rise for the age groups below 35. Early diagnosis, high rate of survival of light-for-date babies and babies with congenital heart defect, and, possibly, exogenous factors working on gametogenesis might be an explanation. To achieve a reduction in incidence, maternal alpha-fetoprotein (AFP)-serum screening for low values may be a possibility. So far, avoidance, but not primary prevention, of Down's syndrome is available. PMID- 2900526 TI - Mutation as a cause of genetic disease. AB - Mutational changes can be conveniently classified into two sorts: those that appear to involve single genes and are generally referred to as gene mutations, and those that involve chromosomal segments containing many genes, or even whole chromosomes, and are referred to as chromosomal mutations. Both of these kinds of mutation occur in germ-cell lineages and contribute substantially to inherited disease, or pre-disposition to disease, and both also occur in somatic cells and contribute to acquired disease. The mutation rates for inherited disease ascribed to mutation in a single gene differ for different genes and are age-dependent. Moreover, a single disease entity, such as haemophilia B, may be the result of any one of a number of different alterations within the gene responsible for the disease. The mutation rate for inherited chromosomal mutation is also age dependent, particularly so in the case of mutations involving alterations in chromosome number. Studies in experimental animals demonstrate that exposure to physical or chemical mutagens results in increasing the incidence of inherited gene and chromosomal mutations. However, such increases have not been unequivocally demonstrated in human populations exposed to known mutagens. Studies on mutation in human lymphoid or epithelial somatic cells clearly demonstrate an increased frequency in cells taken from people exposed to ionizing radiations or chemical mutagens or in cells exposed in vitro. The consequences of such mutations will depend upon their nature and the origins and functions of the cells in which they occur. Of particular importance are mutations influencing cell growth and proliferation, and both gene and chromosomal mutations are implicated as causal factors in the development of human cancers. PMID- 2900527 TI - Experimental work on induced mutations. AB - The detection of changes in mutation rate in human populations remains extremely difficult. Thus estimation of genetic hazards of mutagens to man depends on extrapolation from experimental systems. Germ cells of animals show complex variations in sensitivity to mutagenic effects. Some agents predominantly affect stem cells or other immature germ cells, whereas others mainly affect later germ cell stages. Dose-response relations also vary both with the agent and with the stage or sex of germ cell treated. In man, in addition to single-gene defects and chromosome anomalies, conditions of complex or uncertain inheritance, such as congenital malformations, are clinically important. Genetic theory leaves unclear whether the incidence of these would be affected by a change in mutation rate. Recent research has shown that in mice the incidence of malformations is increased by exposure of the parents to mutagens, but the effect is small. Chromosomal non-disjunction is also clinically important. Again, recent research shows that its frequency can be changed by mutagens, but the effects vary with germ-cell stage. Thus, further research is needed to elucidate the relative contributions of different environmental mutagens to human genetic disease. PMID- 2900528 TI - Diagnosis of human heritable defects by recombinant DNA methods. AB - Recombinant DNA methods provide highly sensitive means for the detection of DNA alterations that lead to human disease mutations. In this paper I shall illustrate the approaches currently available and discuss new technologies that show promise of replacing the present methods. Medical diagnosis by means of recombinant DNA methods has an expanding role in clinical medicine. PMID- 2900529 TI - The prevention and avoidance of genetic disease: summing up. AB - The preceding papers have dealt with major advances in understanding and detecting the mutational basis of human disease. If these advances are to be of practical benefit, systems of effective, efficient and acceptable delivery of the technology to the relevant population groups will need to be planned. In these delivery systems, the key figure is likely to be the clinical geneticist, still a somewhat shadowy figure, difficult to define: a doctor among scientists, and a scientist among doctors. The clinical geneticist, among other duties, acts as a user-friendly interface between the public (including the medical profession) and the conceptually quite difficult fields of modern genetics. Few people in this age of transition to computer literacy will underestimate the importance of a user-friendly interface, without which even the most powerful analytical machines are underused, error prone, or even incomprehensible. PMID- 2900530 TI - Bi-directional changes in sham feeding in the rat produced by benzodiazepine receptor ligands. AB - Both the real and sham intake of a 5% sucrose solution were increased by midazolam (3 mg/kg IP), a benzodiazepine agonist. In contrast, both the real and sham intakes of a 20% sucrose solution were reduced by Ro15-3505 (a benzodiazepine antagonist with weak inverse agonist properties) and by FG 7142 (a beta-carboline inverse agonist). These data demonstrate that drugs acting at benzodiazepine receptors can bi-directionally alter ingestional responses, probably by modulation of the oropharyngeal control of consumption. PMID- 2900531 TI - Plant based antiamoebic drugs; Part II. Amoebicidal activity of parthenin isolated from Parthenium hysterophorus. PMID- 2900532 TI - Medication decisions and the risk of tardive dyskinesia. PMID- 2900534 TI - Recent developments in neurobiology: Part II. Neurotransmitter receptors and psychopharmacology. PMID- 2900533 TI - CSF somatostatin in anorexia nervosa and bulimia: relationship to the hypothalamic pituitary-adrenal cortical axis. AB - The eating disorders, anorexia nervosa and normal weight bulimia, are associated with disturbances of hypothalamic-pituitary-adrenal cortical (HPA) and growth hormone function. Because somatostatin (SRIF) is one of the neuropeptides known to modulate feeding behavior and neuroendocrine systems, we measured cerebrospinal fluid (CSF) concentrations of this peptide in patients with eating disorders. CSF SRIF concentrations in patients with anorexia nervosa, both at low weight and after weight recovery, were similar to those in controls. When normal weight bulimic women stopped binging, they had a modest but significant increase in CSF SRIF. CSF SRIF was not related to plasma growth hormone concentrations but did show relationships to HPA axis hormones. Healthy volunteer women had a significant positive relationship between CSF SRIF and CSF corticotropin releasing hormone (CRH). In underweight anorectics, CSF SRIF was negatively related to both 24-hr urinary free cortisol and plasma cortisol concentrations after dexamethasone, but it was not significantly related to CSF CRH. These relationships more closely resembled those of healthy controls after weight correction. In bulimics, CSF SRIF was positively related to CSF CRH and negatively related to plasma cortisol. Our findings support a previously described relationship between CSF SRIF and HPA axis activity. The differences in SRIF-HPA relationships in anorectics and bulimics may constitute or reflect pathophysiological distinctions between these disorders. PMID- 2900535 TI - The role of molecular biology in psychiatry. PMID- 2900536 TI - The role of adenosine in the central actions of the benzodiazepines. AB - 1. Evidence is presented which indicates that the central actions of the benzodiazepines cannot be fully accounted for by assuming an action only at the GABAA-Cl- channel supramolecular complex. 2. The hypothesis is presented, together with supporting evidence, that inhibition of adenosine uptake can account for many of the actions of the benzodiazepines. 3. New findings showing that Ro 15-1788 and Ro 5-4864 have both potentiative and antagonistic interactions with adenosine are discussed. 4. The proconvulsant beta-carbolines are shown to be adenosine antagonists. 5. The concept that benzodiazepine action may involve several mechanisms is presented. PMID- 2900537 TI - Glutamate transmission and toxicity in Alzheimer's disease. AB - 1. Despite intensive research, the cause of Alzheimer's disease is unknown. 2. Glutamate is the major excitatory transmitter of the cerebral cortex and hippocampus and it appears to have an important role in learning and memory. In addition to its transmitter function, glutamate is a neurotoxin which has been implicated in the pathogenesis of a variety of neurodegenerative disorders. 3. Glutamate toxicity may play a role in the pathogenesis of Alzheimer's disease. 4. Disruption of glutamatergic neurotransmission may account, in part, for the learning and memory deficits of Alzheimer's disease. 5. Labeling of the glutamate receptor complex may allow in vivo diagnosis by positron emission tomography. 6. Glutamate receptor ligands may provide a means of therapeutic intervention in Alzheimer's disease. PMID- 2900538 TI - Blockade of hippocampal dopamine (DA) receptors: a tool for antipsychotics with low extrapyramidal side effects. AB - 1. 32 neuroleptics (NL) and a Ciba-Geigy antipsychotic (savoxepine, CGP 19 486 A) were tested on adult male rats and mice. 2. Interaction with D2 DA receptors was assessed using in vivo (3H)spiperone (SPI) binding in rat hippocampus and striatum. 3. Antipsychotic efficacy of NL was checked by their ability to antagonize apomorphine-induced climbing behavior in mice. 4. We found a good correlation between blockade of DA receptors in hippocampus and antagonism of climbing with both classical and atypical NL. 5. No correlation was found between blockade of DA receptors in striatum and climbing with the atypical NL. 6. It is suggested that NL exerting preferential blockade of hippocampal as compared to striatal DA receptors may show a better dissociation between antipsychotic efficacy and induction of extrapyramidal side effects (EPS) in the clinic. The antipsychotic agent savoxepine, displayed such a favourable profile of action. PMID- 2900539 TI - Benzodiazepine dependent patients and their psychological treatment. AB - 1. 91 patients were referred to a tranquilizer withdrawal clinic. 44 of these entered a withdrawal programme. The characteristics of the patients are described. 2. 72% of patients accepted for benzodiazepine withdrawal had a history of previous psychiatric contact. They also had significantly higher scores on S.T.A.I. than control groups of non-psychotic psychiatric out-patients indicating a considerable psychiatric morbidity prior to withdrawal. 3. 12 patients were treated with psychological group therapy using anxiety management techniques. The outcome of this pilot study showed that 50% of subjects were able to discontinue their benzodiazepines despite previous failures. 4. Patients found learning to cope with symptoms, sharing problems with others and learning to change thoughts the most useful components of the anxiety management package during withdrawal. PMID- 2900540 TI - Super high affinity 3H-para-aminoclonidine binding to platelet adrenoceptors in depression. AB - 1. An assay was developed using sucrose gradient purified platelet plasma membranes which allowed detection, for the first time in patients, of both super high affinity (KD = 17 pM) and high affinity (KD = 1.7 nM) binding sites. 2. Limited Scatchard plot analyses were performed on platelet membranes from depressed patients and controls using 10 pM-2.5 nM 3H-p-aminoclonidine (3H-PAC). 3. Patients (n = 9) were age-paired with healthy control subjects for simultaneous blood drawing, platelet preparation and analysis. 4. All patients were endogenous depressives with Hamilton-Depression scores ranging from 19 to 30 at the time of pre-treatment. Seven of the nine patients were analyzed again at six weeks of treatment with antidepressant medication. 5. Using 60 pM 3H-PAC (a concentration determined to bind predominantly to the super-high affinity receptor state) pre-treatment patient values were higher then paired controls (p = 0.06). Post-treatment analysis of seven of the patients and paired controls showed no differences (p = 0.5) suggesting a normalization of receptor binding following treatment. 6. No differences were observed in platelet yield or morphology or in the percent of other blood cell contaminants in the platelet preparations between patients at pre-treatment and controls. However, the platelet yield was significantly lower in patients post-treatment (p = 0.06). 7. These results are in agreement with two previous studies showing elevated 3H clonidine binding to high affinity sites from depressed patients. The data presented herein suggest that there is a modest 1.25-fold elevated super-high affinity platelet adrenoceptor binding in depressed patients pre-treatment. Receptor binding becomes normal post-treatment. PMID- 2900541 TI - [Somatostatin and its effect in closing intestinal fistulas]. PMID- 2900542 TI - Influence of the autonomic nervous system in the horse urinary bladder. AB - alpha and beta-adrenergic receptors in detrusor muscle and bladder base of horses were investigated by in vitro responses of smooth muscle strips to exogenous agonist and antagonist drugs. Noradrenaline, isoprenaline and salbutamol induced relaxation of detrusor muscle strips which was significantly inhibited by propranolol and butoxamine suggesting that the response is mediated by beta-2 adrenergic receptors. In the urinary bladder base noradrenaline, phenylephrine and B-HT 920 induced strong contractile effects. These contractile responses were inhibited by the alpha antagonist phenoxybenzamine, the alpha-1 selective antagonist prazosin and the alpha-2 selective antagonist yohimbine. The inhibitory action of prazosin was more potent than that observed with yohimbine suggesting that the response in the bladder base of horses is mediated predominantly by alpha-1 adrenergic receptors, although alpha-2 receptors also participate. PMID- 2900543 TI - Further studies on the diagnostic value of gamma-glutamyl transpeptidase and 5' nucleotidase in cattle, sheep and horses. AB - The distribution of 5'-nucleotidase (5'-NT) and gamma-glutamyl transpeptidase (gamma-GT) is similar in the tissues of the sheep, calf and horse, except that there is relatively less gamma-GT in calf liver than in the liver of the other two species. The liver lesion produced by the oral administration of chloroform is similar in the three species and is accompanied by the release of 5'-NT into the plasma of the sheep and calf but not of the horse. Conversely, gamma-GT is released into plasma of the horse but not of the sheep or calf. This difference is not related to the tissue distribution of the two enzymes. The kidney lesion in sheep produced by the intravenous administration of mercuric chloride is accompanied by a reduction in the rate of excretion of an injected dose of inulin and by an increase in the concentration of urea in plasma and in the activity of gamma-GT in plasma and urine. There was no increase in 5'-NT activity in plasma or urine. PMID- 2900544 TI - Use of a monoclonal antibody to detect the F41 fimbrial adhesion of enterotoxigenic Escherichia coli. AB - A monoclonal antibody that identifies a specific epitope on the F41 fimbrial adhesin was used in coagglutination and enzyme-linked immunosorbent assay (ELISA) tests, to identify successfully strains of Escherichia coli expressing the F41 adhesin. The antibody also bound to frozen sections of ileum from piglets infected with an F41 positive E coli demonstrating that the epitope is expressed in vivo. PMID- 2900545 TI - [Value of oral premedication with a non-sedative anxiolytic agent for performing electrophysiological hearing tests. Apropos of 100 cases of patients treated with bromazepam]. PMID- 2900546 TI - [Effect of histamine H2-antagonists on serum gastrin levels in gastric lumen perfused rats]. AB - The effect of histamine H2-antagonists on serum gastrin concentration and histamine-stimulated gastric acid secretion was studied in gastric lumen-perfused rats in which changes in the intragastric pH were limited by using 2.5 mM propionate-succinate buffer as perfusate. The gastric acid secretion was measured by the titration of the acidity of gastric juice with 0.05 N NaOH. The serum gastrin levels were determined in the blood that was obtained simultaneously with gastric juice by radioimmunoassay. The gastric acid secretion was inhibited by these histamine H2-antagonists--cimetidine, famotidine, ranitidine and TZU-0460 administered intravenously. Within the dose-response range of the inhibition of gastric acid secretion, cimetidine and ranitidine increased significantly the serum gastrin levels, but famotidine and TZU-0460 did not. The doses of famotidine and TZU-0460 which were used to increase the serum gastrin levels were found to be higher than those for the maximal inhibition of gastric acid secretion. They also presented a dose-response curve to the serum gastrin levels similar to cimetidine and ranitidine. The findings suggest that histamine H2 antagonists have a potency to increase serum gastrin levels to that of the inhibition of gastric acid secretion. PMID- 2900547 TI - [Clostridium perfringens septicemia]. AB - We report 3 cases of Clostridium perfringens bacteremia with uterine gas gangrene. Clinical presentation included severe infectious syndrome, hemoglobinemia and hemoglobinuria, jaundice, uterine tenderness and hypertension. All 3 cases were first seen with installed renal failure. Diagnosis and modalities of therapy were reviewed. Clostridium perfringens bacteremia with uterine gas gangrene still occur in developing countries. PMID- 2900548 TI - Education and training in gastroenterology. Report from the OMGE symposia at the International Congress of Gastroenterology, Lisbon, Portugal, September 1984, and at the 8th World Congress of Gastroenterology, Sao Paulo, Brazil, September 1986. AB - Gastroenterology is recognized as a speciality in most countries, especially in Europe and North America. The requirements for being acknowledged as a specialist vary from 1 1/2 to 4 years of training and education in gastroenterology in addition to 1-6 years of training and education in internal medicine/surgery. The requirement of theoretical education varying from 40 to 300 h is practiced in some countries only. In some countries training in endoscopy is separated from gastroenterology. A formal examination and post-specialization training program is required in only some of the countries answering the questionnaire. The number of centres per million inhabitants recognized for training and education also varied greatly. The number of specialists per million inhabitants was 3.6 to 15. In the Middle and Far East the organisation of gastroenterology was much inferior to that in Europe and North America because of insufficient education and organization programs and lack of economic support to perform them. The answers from the gastroenterological associations and personal reporters agreed on the following: A speciality in medical and surgical gastroenterology should be established in all countries around the world. Programs for training and education should be agreed upon in recognized teaching and training institutions of gastroenterology, probably of 3 years' duration in combination with a speciality in internal medicine. A gastroenterologist will in most cases be dealing with other diseases as well. The number of specialists per million inhabitants may be estimated to 10, the exact number not being possible to determine at present. In most countries the post-specialization programs were not required but were offered, a problem that has to be clarified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900549 TI - Reports from gastroenterological societies and individual gastroenterologists. PMID- 2900550 TI - Hemorrhagic fever with renal syndrome in Yugoslavia: detection of hantaviral antigen and antibody in wild rodents and serological diagnosis of human disease. AB - Lung tissues from 547 rodents and 26 insectivores captured between 1981 and 1984 in central Bosnia (Fojnica) and central Serbia (Cacak), 2 regions known to be endemic for hemorrhagic fever with renal syndrome (HFRS), were examined for hantaviral antigen by the indirect immunofluorescent antibody technique. Antigen was detected in 17/231 Apodemus flavicollis, 3/187 A. sylvaticus, 1/46 A. agrarius, 4/32 Mus musculus, and 3/28 Clethrionomys glareolus. In addition, antibodies against Hantaan and Puumala viruses were found in serum pooled from 2 C. glareolus captured in Fojnica and 6 Pitimys subterraneus caught in Cacak. Sera of 27 HFRS patients from different parts of Yugoslavia were tested against 3 serotypes of hantavirus. Patients from Bosnia and Serbia had highest titers against Hantaan virus, while patients from Croatia had highest titers against Puumula virus, the agent of nephropathia epidemica. PMID- 2900552 TI - Hematological aspects of infectious diseases II. PMID- 2900553 TI - Infection with HTLV-I and HTLV-II: evolving concepts. PMID- 2900551 TI - Hemorrhagic fever with renal syndrome (nephropathia epidemica) in Norway: seroepidemiology 1981-1985. AB - An indirect fluorescent antibody technique (IFAT) was applied to serologically confirm the clinical diagnosis in 507 nephropathia epidemica (NE) suspected patients. Hantaan virus (HV), the agent of Korean hemorrhagic fever, which is serologically related to the NE agent, was used as antigen. Both IgG and IgM reactions were detected. High levels of IgG antibodies to HV were common, even in the acute phase of illness. Over a 5-year period, a total of 35% of the NE suspected patients revealed antibodies to HV, but this varied considerably in the different years. In 2 endemic areas the serological confirmation of the NE diagnosis was 60%. 82% of the seropositive NE patients lived in 4 endemic areas. The bank vole (Clethrionomys glareolus) was common in all areas and predominant in 2. The wood mouse (Apodemus sylvaticus) was abundant in the other 2. In years with high bank vole population, the number of seropositive NE cases increased, with a peak in October/November. When the bank vole population was low, the relatively few seropositive NE cases occurred more regularly throughout the year. Subclinical infections were common. Antibodies to HV were detected in 74% male and 26% female NE patients, but the ratio varied between age groups. PMID- 2900554 TI - Neuroleptic malignant syndrome--report of a case. PMID- 2900555 TI - Efficacy of histamine H1 and H2 receptor blockers in the anesthetic management during operation for hydatid cysts of liver and lungs. AB - We studied the effects of preoperative administration of histamine (H1 and H2) receptor blockers on hemodynamic changes in two groups of patients having operation for hydatid cyst. Patients in group 1 received no antihistaminics, whereas those in group 2 were pretreated with both H1 (diphenhydramine) and H2 (cimetidine) receptor blockers. Even though there were significant hemodynamic responses associated with spillage of hydatid cyst contents in both groups, the hemodynamic changes were significantly less in the patients who had received histamine receptor blockers. We conclude that the preoperative administration of H1 and H2 receptor blockers to patients having hydatid cyst surgery is beneficial. PMID- 2900556 TI - P-fimbriated E coli urinary tract infection. PMID- 2900557 TI - Application of biotechnology in the identification of filarial larva in mosquitoes. AB - Current methods for detecting and identifying filariae in mosquitoes are laborious and time consuming. With today's technology, we can reasonably expect development of rapid, sensitive and specific assays for detecting and identifying filariae in naturally infected mosquito populations. Progress in developing such assays is reviewed. PMID- 2900558 TI - Drugs in sport. The first 5 years of testing in South Africa. AB - Since 1983 screening procedures have been developed to detect prohibited substances in urine specimens collected from competitors in sport. Gas chromatography is used for the detection of stimulant drugs and gas chromatography/mass spectrometry for the detection of anabolic steroids. Of 679 urine samples analysed, a positive result was obtained for 45 (6.6%). Fencamfamine was the stimulant most frequently detected, while the ephedrines as a group accounted for 18 positive samples. These findings indicate the necessity to continue the monitoring of drug use and abuse in sport. PMID- 2900559 TI - Health implications of petroleum distillate ingestion. AB - The authors discuss the clinical approach to the management of hydrocarbon ingestions, including the role, implementation, and type of gastric decontamination utilized; the extent of medical evaluation, observation or hospitalization required; and the appropriate therapy for hydrocarbon pneumonitis. An appendix covers myocardial sensitization following inhalation abuse of hydrocarbons. PMID- 2900561 TI - Pericarditis due to Bacteroides melaninogenicus secondary to a teratoma. PMID- 2900560 TI - Effect of azelastine on bronchoconstriction induced by histamine and leukotriene C4 in patients with extrinsic asthma. AB - Azelastine, a new oral agent with antiallergic and antihistamine properties, has been shown to inhibit the effect of histamine and leukotriene (LT) in vitro, though not a specific leukotriene receptor antagonist. The effect of both a single dose (8.8 mg) and 14 days' treatment (8.8 mg twice daily) with azelastine on bronchoconstriction induced by LTC4 and histamine has been examined in 10 patients with mild asthma in a placebo controlled, double blind, crossover study. LTC4 and histamine were inhaled in doubling concentrations from a dosimeter and the results expressed as the cumulative dose (PD) producing a 20% fall in FEV1 (PD20FEV1) and 35% fall in specific airways conductance (PD35sGaw). The single dose of azelastine produced a significantly greater FEV1 and sGaw values than placebo at 3 hours, but this bronchodilator effect was not present after 14 days of treatment. Azelastine was an effective H1 antagonist; after a single dose and 14 days' treatment with placebo the geometric mean PD20FEV1 histamine values (mumol) were 0.52 (95% confidence interval 0.14-1.83) and 0.54 (0.12-2.38), compared with 22.9 (11.5-38.3) and 15.2 (6.47-35.6) after azelastine (p less than 0.01 for both). LTC4 was on average 1000 times more potent than histamine in inducing bronchoconstriction. Azelastine did not inhibit the effect of inhaled LTC4; the geometric mean PD20FEV1 LTC4 (nmol) after a single dose and 14 days' treatment was 0.60 and 0.59 with placebo compared with 0.65 and 0.75 with azelastine. The PD35sGaw LTC4 was also unchanged at 0.66 and 0.73 for placebo compared with 0.83 and 0.74 for azelastine. Thus prolonged blockade of H1 receptors did not attenuate the response to LTC4, suggesting that histamine and LTC4 act on bronchial smooth muscle through different receptors. Four patients complained of drowsiness while taking azelastine but only one who was taking placebo and three patients complained of a bitter, metallic taste while taking azelastine. PMID- 2900562 TI - [Cardiovascular effects of timolol, carteolol, metipranolol, betaxolol collyres in the aged patient]. PMID- 2900563 TI - Purification of Chironex fleckeri venom components using Chironex immunoaffinity chromatography. AB - A comparison of the purification of the nematocyst venom of Chironex fleckeri by affinity immunochromatography using 13 different monoclonal antibodies was made. Varying degrees of purification of mouse lethal factor, hemolysin and dermonecrotic factors, as well as antigen positive proteins were achieved with each of the monoclonal antibodies. Although the protein curves of the chromatography were similar, each of the monoclonal antibody columns had a distinctive pharmacological and SDS-PAGE profile. At least two hemolysins (120,000 and 70,000 molecular weight), two dermonecrotic principles (120,000, less than 120,000) and three lethal factors (120,000, 70,000 and 14,500 molecular weight) were detected. The degree to which aggregation and fragmentation affects the molecular weights of these proteins is not known. It appears that multiple pharmacological activities are present within the same molecule since it is only with great difficulty that a pharmacological activity can be assigned to a specific molecular weight. PMID- 2900564 TI - Antihypertensive effect of beta blockade in renal transplant recipients with or without host kidneys. AB - Host kidneys may contribute considerably to hypertension after renal transplantation. Their role in sustaining hypertension is more prominent if glomerulonephritis (GN) than if interstitial nephritis (IN) is the original renal disease. We compared the antihypertensive effect of beta-blockade in IN (n = 10) and GN (n = 19) hypertensive renal transplant recipients with host kidneys in situ with those who had undergone bilateral nephrectomy (BN, n = 10). Pretreatment blood pressures were comparable in BN, IN, and GN patients, being 165 +/- 6/108 +/- 3, 172 +/- 5/104 +/- 3, and 161 +/- 3/104 +/- 1, mmHg, respectively. Blood pressure did not change on beta-blockade in BN patients, whereas it decreased significantly more (P less than 0.001) in GN than in IN patients, changes of mean arterial pressure being -107 +/- 1.0, -14.9 +/- 1.3, and -6.8 +/- 1.6%, respectively. This failure to respond to beta-blockade in patients without host kidneys may be related to low activity of the renin angiotensin system or to functional denervation of the grafted kidney. Further investigations of this phenomenon may clarify the mechanism of antihypertensive action of beta-blockade as well as the nature of hypertension after renal transplantation. PMID- 2900565 TI - Frequency of HLA-DRBr in renal patients awaiting transplantation. PMID- 2900566 TI - Use of the Candela laser in the ureter. AB - The Candela pulsed dye laser is safe and effective. Complications are few and related more to the ureteroscopy than to the laser. Current results in the lower ureter utilizing primarily ultrasound as a method of power lithotripsy have been excellent, and it is difficult to see how lasertripsy will improve on these. The importance of the laser is related to its small size and its flexibility. This will permit simpler access to the stone employing instruments such as small caliber rigid ureteroscopes and small steerable flexible instruments. If these instruments can be passed without ureteral dilatation, access to the stone will be safer, and they may well extend the range of stones regularly susceptible to ureteroscopic removal. PMID- 2900567 TI - Use of pulsed Nd:YAG laser in the ureter. AB - An Nd-YAG laser of 1064-nm wavelength, 8-nanosecond pulse duration, and single pulse energy of 20 to 80 mJ can create shock waves with a peak pressure of 1000 bar in less than 4 nanoseconds. The safety of this laser has been demonstrated in cultured cells, whole blood, and porcine urothelium. Clinically, ureteral calculi have been removed from 24 of 27 patients. PMID- 2900568 TI - The impact of laparoscopy on modern urologic practice. AB - The original concept of laparoscopy developed as a branch of cystoscopy. Since the use of the Nitze cystoscope at its inception, laparoscopy has kept pace with the innovations in our cystoscopic inventory. The recently emerging interest of urologists in utility of the laparoscope for a variety of urologic surgery is a welcome renascence of this procedure, which has been used mainly by our gynecologic colleagues, in part because of our own lack of pursuit in its development. Laparoscopy should now become an integral part of our urologic teaching and practice. PMID- 2900569 TI - Effects of pulsed dye laser lithotripsy on tissues. Experimental study in the canine ureter. AB - This experimental study demonstrates the absence of irreversible tissue damage after lithotripsy with a pulsed dye laser. The absence of thermal damage with this laser is due to the beam divergence capacity at the end of the fiber and to the short pulse, which generates very low thermal effect. These results as a whole confirm the safety of the pulsed dye laser and indicate that it can be used for clinical treatments in humans. PMID- 2900570 TI - MRI of the scrotum. AB - Surface coil magnetic resonance (MR) imaging of the scrotum allows differentiation of the testis, epididymis, and spermatic cord. Intratesticular and extratesticular lesions are demarcated by the tunica albuginea. The sensitivity of MR is very high for detection of scrotal abnormalities but is non specific since it is unable to distinguish primary testicular tumors from benign lesions. Undescended testes which lie proximal and distal to the internal inguinal ring are well visualized by MR imaging. The advantages of MR imaging in locating undescended testes is that it is noninvasive, without ionizing radiation, and capable of multiplanar images. PMID- 2900571 TI - Use of the muscle relaxant vecuronium in a myasthenic dog. PMID- 2900572 TI - The intraclonal and interclonal phenotypic heterogeneity in a rhabdomyosarcoma cell line with abortive imitation of embryonic myogenesis. AB - Three distinct subpopulations (A, B, C) derived from a dimethylbenzanthracene induced rat rhabdomyosarcoma were established as permanent cell lines. Although the clonal nature of each of these subpopulations was confirmed by repeated recloning procedures, a striking intraclonal phenotypic heterogeneity was observed. By means of immunofluorescence microscopy and transmission electron microscopy, it could be shown that these subpopulations closely recapitulate stages of embryonic rhabdomyogenesis both in vitro and in vivo, but differ in their particular range of maximum differentiation. Embryonic rhabdomyogenesis is imitated most perfectly by subpopulation C, in which multinuclear myotubes are formed in vitro by fusion of mononuclear cells, and alpha-sarcomeric actin is expressed in the multinuclear cells and in a few mononuclear cells. After retransplantation in vivo, subpopulation C further proceeds in fine structural differentiation, now exhibiting myofibrils with a sarcomeric organization in the myotube-like giant cells. The cells of subpopulation B do not exceed the stage of mononuclear desmin-positive cells in vitro, but synthesize thin and thick myofilaments after retransplantation in vivo. The cells of subpopulation A recapitulate embryonic rhabdomyogenesis least successfully being confined to the stage of mononuclear desmin-positive cells. Thus, the coexistence of diverse subpopulations and the cellular maturation within these subpopulations together contribute to the phenotypic heterogeneity of rhabdomyosarcomas. PMID- 2900573 TI - Intravesical BCG administration in the guinea pig. A histomorphological study. AB - Intravesical BCG administration is used as an adjuvant therapy after transurethral resection for superficial bladder cancer in man. The mechanisms of its antitumor activity are not known. The aim of this study was to characterize the histomorphological changes in various organs of the guinea pig after intravesical BCG administration. The BCG preparation used was BCG-RIVM, a Dutch BCG preparation. Instillations were performed in previously undamaged bladders weekly for 6 consecutive weeks and lasted 30 min or 1 h. Different doses were used ranging from 10(3) culturable particles (c.p.) to 5 x 10(7) c.p. of BCG. After 6 weeks, the animals were killed and postmortem examination was performed. The bladder wall, retroperitoneal lymph nodes, spleen, liver, lungs and distant lymph nodes were examined histologically. The BCG therapy, with a dose of 10(6) culturable particles and higher, induced an inflammatory reaction consisting of mononuclear infiltrates in the subepithelial tissue of the bladder wall. In approximately 50% of the animals investigated, the infiltrates were accompanied by non-caseating granulomatous lesions indicated by the presence of epithelioid cells. In general, the epithelial layer of the bladder showed no visible alterations. Similarly, a granulomatous inflammatory reaction was observed in the first retroperitoneal (iliac) lymph nodes draining the bladder. Granulomatous lesions were occasionally also present in liver and lung. In three of the 29 animals investigated, lesions were present both in liver and lungs, and in two of these three animals a granulomatous reaction was observed in the spleen and distant lymph nodes indicating a generalized inflammatory response induced by BCG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900575 TI - Stereological estimates of nuclear volume in normal mucosa and carcinoma in situ of the human urinary bladder. AB - The nuclear volume of the epithelial cells in the human urinary bladder mucosa has been estimated using point sampled intercepts in vertical sections (local vertical windows). The study included 27 specimens: ten from normal bladder mucosa, five from inflamed mucosa, seven from mucosa with flat grade II lesions and five from mucosa with flat grade III lesions. After standard fixation, embedding, sectioning and haematoxylin-eosin staining an unbiased estimate of the mean volume of nuclei sampled with a chance proportion to the volume = vV = pi/3 x (l0)3 was calculated using a frame for orientating the linear test probe in vertical sections. Here l0 is the length of the intercept through a test point hitting a nucleus measured in a random direction through the test point. The weighted mean nuclear volume of bladder mucosa with grade II and grade III lesions (537 microns 3 and 494 microns 3 respectively) was significantly larger than the weighted mean nuclear volume of normal (133 microns 3) and inflamed bladder mucosa (182 microns 3). This simple and fast estimation of nuclear volume seems to provide objective data useful in discriminating between neoplastic and non-neoplastic lesions of the bladder mucosa. PMID- 2900574 TI - Developmentally regulated expression of the calcitonin gene related peptide (CGRP) in rat lung endocrine cells. AB - Calcitonin (CT) and the calcitonin gene-related peptide (CGRP) are generated by alternative RNA processing from a single CT/CGRP gene. Recently, we reported the existence of CGRP-immunoreactivity and CGRP mRNA in endocrine cells or Kulchitsky (K) cells of human and rat lung [Wada et al. 1987b]. In this report, an examination was made of developmental changes in the expression of the CGRP gene in rat lungs by immunohistochemistry, radioimmunoassay (RIA) and Northern hybridization. CGRP-positive K-cells in lung tissue appeared on the 18th day of gestation. Their number was greatest on the 20th day of gestation and then decreased postnatally. The level of CGRP in rat lung was found to be highest in a 1-day-old neonate by RIA. In the Northern hybridization of rat lung using the CGRP 3' non-coding region (exon 6) of the first human CT/CGRP gene as the probe, 1.0 kilobase (kb) CGRP mRNA was found to be abundant on the 20th day of gestation and in a 1 day-old neonate. It thus appears that CGRP in rat lung is essential for pulmonary adaptation at birth and/or from the last intrauterine stage to the early neonatal period. PMID- 2900576 TI - Sex chromatin analysis of lymphocytes invading host organs in transfusion associated graft-versus-host disease. AB - We report a method of sex chromatin analysis of lymphocytes separated from host organs in transfusion-associated graft-versus-host disease (GVHD), which enabled the demonstration of invasion by donor lymphocytes. The lymphocytes examined were separated from deparaffinized tissue blocks of skin, spleen and bone marrow from two female patients with transfusion-associated GVHD by incubation in 0.5% pepsin. The tissues had been removed at autopsy and fixed in formalin. Sex chromatin analysis was performed by fluorescence microscopy on separated lymphocytes stained with 0.005% quinacrine dihydrochloride. By this means Y chromatin-positive (i.e. male) lymphocytes were demonstrated in the skin, spleen and bone marrow of both female patients. PMID- 2900577 TI - Morphological changes in a human scirrhous gastric carcinoma cell line (KATO-III) when cultured in collagen-coated dishes. AB - The morphological differences between cells of a human scirrhous gastric carcinoma cell line (KATO-III) cultured in plastic dishes and in collagen-coated dishes were examined by phase-contrast and electron microscopy. When KATO-III cells were inoculated into plastic dishes, a few cells became attached to the surface of the dishes and the rest remained in suspension. However, when they were inoculated into collagen-coated dishes, they all remained in suspension. In both types of dish, most of the cells in suspension were single although a few were in clusters. The cells in suspension in collagen-coated dishes differed in morphology from those in the plastic dishes. They had abundant cytoplasm, well developed Golgi complexes, and many microvillus-like cell protrusions. Moreover, they had hemidesmosome-like and desmosome-like structures on their surface and an increased amount of intracytoplasmic desmosome-like structures. The cells in clusters in the collagen-coated dishes were closely connected by junctional complexes, such as tight junctions, desmosomes and interdigitations, whereas those in plastic dishes were linked only by desmosomes. These results suggest that collagen affects the morphology of human scirrhous carcinoma cells. PMID- 2900578 TI - LaCrosse virus gene expression in mammalian and mosquito cells. AB - LaCrosse virus infection of mammalian BHK cells is highly cytopathic, whereas that of mosquito C6/36 cells is asymptomatic and persistent. When the individual mRNAs and their genome segments are followed in parallel infections, cytopathic effects were found to correlate with the rate of synthesis, but not the accumulation, of the viral RNAs. The change from the acute to the persistent phase of the infection in C6/36 cells was found to take place at 24 hr p.i., at which time genome and N protein synthesis was severely reduced, even though mRNA levels remained high. When the persistent infection was followed for 72 days, the total amounts of genomes and their relative proportions were found to fluctuate greatly, whereas mRNA levels were either severely reduced or undetectable. DI genomes could not be detected during this time. The self-limiting nature of the mosquito cell infection appears to be due the translational control of N protein synthesis. PMID- 2900579 TI - [Histochemical studies of lipid metabolism in Entamoeba histolytica (Schaudinn, 1903)]. PMID- 2900580 TI - [Reintervention in C-cell carcinoma]. AB - Cervical re-exploration in persistent medullary thyroid cancer usually fails to normalize serum calcitonin levels, which is the most sensitive criterion of tumour-free status (2 out of 21 patients in our re-exploration series). Positive lymph nodes - even at an early tumour stage - seem much more important (postoperative normal serum calcitonin: 86% in the occult tumour group, 71% in patients with palpable primary tumour and negative lymph nodes, as opposed to only 18% with a palpable cervical mass and positive lymph nodes). However, local re-exploration in case of persistent medullary thyroid cancer seems to offer a possible curative chance for the control of recurrence, especially after inadequate primary surgery. In cases without visible distant metastases a marked reduction in serum calcitonin level may be expected (21% of the preoperative level for stages N1 and N2 and 16% for stage N3 on average). In patients with elevated calcitonin levels after stimulation as sole indicator of persistent tumour the indication for reoperation should be handled cautiously. Thus, in 3 out of 5 patients with occult medullary thyroid cancer diagnosed only on the basis of venous sampling who were subjected to multiple cervical re-explorations, distant metastases were subsequently found during follow-up. PMID- 2900581 TI - Reoperative parathyroid surgery. AB - Reoperation for persistent or recurrent primary hyperparathyroidism immediately connotes a complex clinical management problem. Successful cure of hypercalcemia is less frequent whereas complications are more common compared to initial explorations. Of 212 patients operated on at the Mayo Clinic from 1978 through 1986, 189 (89%) were cured. Sporadic disease, multiple endocrine neoplasia, and familial hyperparathyroidism were found in 183 (87%), 20 (9%), and 9 (4%) patients, respectively. Prior to the most recent reoperation, these patients had undergone from one to five operations. Preoperative localization examinations were performed in 192 patients (91%). Cervical high-resolution, real-time ultrasonography, computed tomography, and thallium-technetium scintigraphy had sensitivity rates of 87%, 56%, and 71%, respectively. When the tumor was localized preoperatively, the operative time and cost were significantly reduced compared to nonlocalized tumors. Cervical reexploration only was required in 154 (72%), combined cervical and mediastinal exploration occurred in 46 (22%), and mediastinal exploration only was performed in 12 (6%). There was no perioperative mortality; permanent hypoparathyroidism developed in 33 patients (16%), and six patients (2.9%) suffered permanent unilateral vocal cord paralysis. Anatomically, the most frequent site to find a missed parathyroid adenoma was in the normal location. The large majority of these glands were removed through a cervical incision although, on occasion, they were retracted from the anterior superior mediastinum or the low tracheoesophageal space. These data confirm that reoperative parathyroid surgery can be performed safely, with a rather high degree of success, but too-frequently results in a lifetime morbidity of hypoparathyroidism. PMID- 2900582 TI - [Reinterventions for hyperparathyroidism in multiple endocrine adenopathy]. AB - Six out of a series of 10 patients with hyperparathyroidism associated with an MEA type I syndrome were treated by subtotal parathyroidectomy with resulting normocalcaemia over a follow-up time of one to 7 years. Three patients with repeated previously unsuccessful operations underwent total parathyroidectomy with simultaneous autotransplantation. The first type of operation remains our first choice, while the radical approach with forearm transplantation is reserved only for recurrent surgery for various reasons. PMID- 2900583 TI - Insulinoma: the value of intraoperative ultrasonography. AB - Ideally, surgical exploration for insulinomas would be met with uniform success in both finding and removing the tumor, incurring no postoperative mortality or morbidity. In reality, however, insulinomas remain undetected by even experienced surgeons in 10 to 20% of patients, including present-day series. Additionally, postoperative complications may occur in 10 to 25% of patients, principally related to the pancreatic dissection. Although dispensing with any attempt to preoperatively localize the tumor has been advocated, most authors agree that localization efforts are necessary and helpful. To review the results and surgical implications of current localization techniques, 41 adult patients who were surgically treated for insulinomas at the Mayo Clinic from 1980 through June 1987, were reviewed. Tumor size ranged from 5 mm to 4 cm, and the sensitivity of tumor localization using arteriography, computed tomography, preoperative and intraoperative ultrasonography were 55%, 27%, 59%, and 90%, respectively. Since the introduction of intraoperative ultrasonography into our clinical practice in 1982, all 29 of our adult patients' insulinomas have been identified with a combination of this technique and palpation by an experienced surgeon. There were no false positive interpretations with intraoperative ultrasonography, and tumors were imaged in four patients that were not palpable. In 18 of these 29 (62%) patients, the information gleaned from the images appeared to influence the surgical management. While there is no substitute for exploration by an experienced surgeon, his ability is enhanced by the addition of both preoperative and intraoperative ultrasonography. PMID- 2900584 TI - [Ofloxacin in therapy of "resistant" duodenal ulcer. A pilot study]. AB - Since its description in 1983 Campylobacter pylori (C.p.) has been discussed as possible pathogenic factor at least in duodenal ulcer disease. The therapeutic combination of H2-receptor-antagonists (= H2-RA) and ofloxacin (Tarivid) has shown to heal resistant duodenal ulcers in some preliminary cases, which did not respond to a three month standard dosage treatment with H2-RA. This paper describes the results of twelve patients whose duodenal ulcers were resistant to H2-RA. C.p. was detected in all patients before therapy. The combined treatment with ofloxacin and H2-RA healed the duodenal ulcers within 2 weeks in 6 patients, within 4 weeks in 2, and within 6 weeks in 4 patients as proven by fortnightly performed endoscopic controls. At the end of therapy C.p. was not detected in 11 of 12 patients. The MIC's of ofloxacin for C.p. ranged from 0.5-1 microgram/ml in six investigated patients. The results suggest a possible pathogenic role of C.p. in duodenal ulcer disease. PMID- 2900585 TI - [Treatment of chronic non-secretory diarrhea in ileostomy with the long-acting somatostatin analog SMS 201-995]. AB - A patient with chronic refractory non-secretory diarrhea following ileostomy was treated with the long acting somatostatin analogue SMS 201-995. Under treatment with somatostatin stool weights were drastically reduced and electrolyte dysbalance was normalized within a few days. This case report shows that somatostatin is also therapeutically effective in non-secretory diarrhea. PMID- 2900586 TI - Modern screening strategies in analytical toxicology with special regard to new benzodiazepines. AB - Screening procedures for the detection of toxicologically relevant substances have become of ever-increasing importance due to the rapid development of new substances. Identification methods must be simple, sensitive, and practicable. This article describes standardized chromatographical (corrected Rcf values, retention indices) and immunological methods (enzyme-multiplied immunoassay technique, fluorescent polarization immunoassay) with special regard to the screening of some newer benzodiazepines, a class of substances that is still expanding. Some of these new compounds may be integrated in well-known screening procedures (via aminobenzophenones and detection by the Bratton-Marshall reagent); others require special concepts for detection. The problems are indicated and discussed, including the use of high-pressure-liquid chromatography and mass spectrometry; recommendations are given. PMID- 2900588 TI - Effects of the alpha-adrenoceptor antagonists phentolamine, phenoxybenzamine, and idazoxan on sympathetic blood flow control in the periodontal ligament of the cat. AB - Blood flow changes in the periodontal ligament (PDL) were measured indirectly by monitoring the local clearance of 125I- during electric sympathetic nerve stimulation or close intra-arterial infusions of either noradrenaline (NA) or adrenaline (ADR) before and after administration of phentolamine (PA), phenoxybenzamine (PBZ), or Idazoxan (RX). At the doses used in the present study, PA was the only antagonist that significantly reduced the blood flow decrease seen on activation of sympathetic fibers, although PBZ also reduced this response. Idazoxan, however, did not induce the consistent effect on blood flow decreases seen on sympathetic activation. All three alpha-adrenoceptor antagonists almost abolished the effects of exogenously administered NA and ADR. The results suggest the presence of functional post-junctional adrenoceptors of both the alpha 1 and alpha 2 subtypes in the sympathetic regulation of blood flow in the PDL of the cat. A component of the response elicited by electrical sympathetic stimulation appeared to be resistant to alpha-adrenoceptor blockade. Administration of guanethidine (which inhibits further release of NA and neuropeptide Y) after PA abolished this residual sympathetic response. PMID- 2900589 TI - [Alloplastic replacement of the anterior cruciate ligament in chronic instability -indications and technic]. AB - Since August 1980, missing or no longer present cruciate ligament structures have been replaced in many patients suffering from chronic instability of knee-joint ligaments, by an implanted ligament made from Trevira hochfest. 158 operations of this kind were supervised by the author. Although results have been good so far, the indication for such an operation should be extremely restricted. The isolated replacement of the anterior cruciate ligaments in chronic instability is an ideal application field. Detailed attention is given to the implantation technique aiming at restoring permanent stability. PMID- 2900587 TI - Neuropathology of Rett syndrome. AB - Rett syndrome is an increasingly recognized progressive disorder in females, commencing in infancy and characterized by autistic behavior, gait ataxia, stereotyped movements, seizures and generalized growth and mental retardation, possibly associated with disorders of central biogenic amine synthesis. The gene locus and pathogenesis of Rett syndrome are unknown. Autopsy studies in nine girls dying between 4 and 17 years, and sural nerve and muscle biopsies from two girls aged 3 and 17 years showed: (1) diffuse cortical atrophy/micrencephaly, with a decrease in brain weight by 12% to 34% of age-matched controls, apparently related to the duration of the disorder; (2) mild diffuse cortical atrophy with increased amounts of neuronal lipofuscin and occasional mild gliosis, but without signs of a storage disorder; (3) underpigmentation of the zona compacta nigrae, which showed fewer well-pigmented neurons for age and fewer melanin granules per neuron, while total numbers of nigral neurons and the substructure of neuromelanin were normal for age. No pathological changes were seen in other transmitter-specific brain stem nuclei; (4) immunoreactivity for tyrosine hydroxylase was slightly reduced in nigral and hypothalamic neurons, and the pituitary gland showed decreased immunoreaction for prolactin and growth hormone; (5) ultrastructurally, in frontal cortex and caudate nucleus, isolated abnormal neurites and reactive or degenerative axonal swellings were seen; the latter are possibly related to the nigral changes, suggesting some dysfunction of the dopaminergic nigrostriatal system, which is supported by neurochemical data; (6) preliminary biochemical studies revealed increased beta-endorphines in thalamus and cerebellum; (7) peripheral nerves demonstrated increase in small fibers without demyelination and increased numbers of neurofilaments in axons, suggesting distal axonopathy, while skeletal muscle showed alterations in the sarcoplasmic reticulum with circular profiles in the Z-filaments. These nonspecific changes may be interpreted as early signs of denervation. The variety of lesions in the central, neuroendocrine and peripheral neuromuscular systems in Rett syndrome are discussed with regard to their clinical and biochemical significance. PMID- 2900590 TI - [Assessment of axis deviation following tibial intramedullary nailing in the standard roentgen image]. AB - Evaluation of 87 fixations of the lower leg revealed that standard x-ray film safely enables accurate determination of defective axial and lateral positioning. Assessment of rotatory malpositioning is unsafe and not likely to yield accurate results. The only possibility is to take the x-ray film of the fixed foot; this enables conclusions from measurements performed on the x-ray film with the metal still implanted and the fixation still in place, as reference parameters. Detailed analysis of the x-ray films, however, revealed even further results: delayed and disturbed healing of bone fractures can be detected early from the mechanical measurement data on the x-ray film, so that correction of the fixation nail can be made well in time. Cases treated in this way healed properly and in a well-adjusted manner. Corrections performed with the fixation nail were pseudoarthroses (5 cases), 4 of which healed without complications whereas one healed after removal of the nail and conservative aftercare. Fractures in the distal part of the lower leg seem to be particularly critical. Because of the close proximity of the ankle joint, unsatisfactory stability will result if the nail end is too short. PMID- 2900591 TI - [Principles of intramedullary nailing of the femur and tibia]. AB - The interlocking nail technique is a perfected method to stabilise even complex shaft fractures of tibia and femur. There are some advantages of this technique compared with Kuntscher's intramedullary nailing, such as avoidance of telescoping and rotation of the fragments. In view of the principles of interlocking nailing and some hints on indication, as given here, the orthopaedic surgeon will obtain good results in the treatment of shaft fractures when proceeding as described. PMID- 2900592 TI - [Bundle nailing--an evaluation after 27 years]. AB - The development of modern osteosynthetic procedures has made the use of bundle nailing uncommon. Bundle nailing is restricted to extraordinary situations, but when indication is correct, it is superior to alternative procedures. From a current viewpoint only two indications remain: one are the fractures of the humeral shaft which cannot be treated conservatively, and the second are fractures of the femur in children if serious complications endanger conservative treatment. Simple instruments and implants as well as simple technique produce excellent results in the hands of experienced surgeons even if seldom performed. The rate of relevant complications for the above mentioned indications was 0.91% in a total of 560 bundle nailings; those were complications which either led to reoperation or negative effects on function. PMID- 2900594 TI - [Polytrauma and femoral fracture]. AB - From 1976 to 1986 1.003 polytraumatized patients were treated at our institution. 88% had suffered fractures of spine, pelvis and limbs. Of particular relevance are the femoral fractures (36% of all cases) in the management of those patients. In not adequately immobilized femoral fractures the rate of general and local complications in this group is elevated. Impaired microcirculation and the required high doses of analgesics can lead to an increased risk of eventually lethal ARDS. From 1976 to 1983 we used the conventional approach and stabilized femoral fractures using plates and IM nails. Due to the time required for the operation, the eventual blood loss and the invasiveness of the operation, we could operate only on 44% of the femoral fractures within the first 24 hours. In 1984 we introduced the DAF device in our service and used it in compound femurs and unstable patients with femoral fractures. In the other cases the locking nail (GK Nail) was used. With this concept we managed to increase the rate of surgery of femoral fractures in polytrauma victims within the first 24 hours to 80%. Further assessment of the date showed a significant drop of 27.3% in mortality, mainly due to a decreased rate in late ARDS-related deaths. The advantage of the DAF concept in the stabilization of these fractures in polytrauma victims we see in the less time consuming fixation, the minimal blood loss, easier ICU care and fewer local complications. The DAF device is used as a definitive management tool and does not generally require a change to another method of fixation. PMID- 2900593 TI - [Indications and osteosynthesis procedures in humeral shaft fractures]. AB - In the therapy of fractures of the humeral shaft, the individual patient's total condition should be taken into consideration when selecting the adequate method of treatment. Conservative treatment of humeral shaft fractures is still preferred, and Sarmiento's functional therapy has expanded the therapeutic possibilities. The decision for operative treatment is clarified by dividing the indications into the following categories: absolute, relative and recommended indications. In order to reduce complication rates and to ensure stability, we chose among three osteosynthetic procedures: 1. Bundle nailing. 2. Compression plate. 3. Fixateur externe (De Bastiani's mono-fixateur). In simple fractures of the shaft, bundle nailing is an effective and low-risk treatment. Compression plate is indicated in the presence of radial nerve palsy and in very distal shaft fractures. In open fractures and fractures with accompanying blood vessel damage, we favour stabilization with the De Bastiani's unilateral fixateur externe. PMID- 2900595 TI - [Results of surgical treatment of pelvic fractures in polytraumatized patients]. AB - High-speed accidents involving automobiles and two-wheeled vehicles with resultant entrapment and crush injuries have led to an ever-increasing incidence of pelvic fracture within the realm of multiple trauma. Between the years 1982 and 1986 ninety-eight cases of pelvic fracture were operatively stabilised by the Department of Surgery and the Outpatient Department of the Technical University, Klinikum Rechts der Isar, Munich, West Germany. This paper is a report on fifty five of these patients who were discovered to have suffered additional multitrauma. Independent from those patients found to have sustained multitraumatisation, twenty-four cases of isolated acetabulum fracture as well as four instances of pelvic ring fracture and one fracture of the pelvic brim were also documented. Combinations of the above mentioned fractures were uncovered in twenty-six patients. With fifty-four of the fracture injuries, osteosynthesis was carried out while in one case primary alloarthroplasty was deemed necessary. Following a mean post-treatment period of twenty-six months forty-five of the patients were objectively evaluated for results of treatment according to the methodology of Merle d'Aubigne. 70% of those patients assessed were rated with a "good" result. At the time of follow-up thirty-five (78%) of the forty-five reexamined individuals reported to be once again employed. Early operative treatment along with internal stabilisation and prompt initiation of physiotherapy have proved decisive in obtaining a favourable postoperative result. PMID- 2900596 TI - [Use of arthrosonography in the diagnosis of Tossy injuries of the shoulder joint]. AB - In a pilot study specificity and sensibility of ultrasonics on Tossy III lesions were tested, and that in 20 cases of guaranteed intact acromioclavicular joints and 22 cases of radiologically diagnosed Tossy III lesions with a following operative control. Additionally in these 22 cases the contralateral acromioclavicular joints were also examined by ultrasonics. All examinations were registered on video tape. With it in a single blind test the exact diagnosis was made in all cases. The diagnosis was based on ultrasonic findings as visible instability, unevenness of the joint line, haematoma formation with ligament stumps. Compared to radiologic diagnostics ultrasonics do not demand cooperative patients or special postures for the examination. A proved accuracy in the diagnosis and the capability of further extension of this technique are of clinical importance. A differentiation of various grades of Tossy lesions is possible. PMID- 2900597 TI - [Subcapital correcting humerus osteotomy in post-traumatic malposition of the humerus head]. PMID- 2900598 TI - New ranitidine analogues containing the 2-aminobenzimidazole moiety: in vivo and in vitro histamine H2-receptor blocking activity. AB - The paper reports the pharmacological profile of a new series of ranitidine analogues in which the diaminonitroethene group is replaced by the 2-amino-5(6) substituted and unsubstituted benzimidazole moieties. These derivatives show a histamine H2-receptor blocking activity comparable to that of the model both in vitro (KB on atria 0.16-1.15 microM) and in vivo (ID50 on the perfused stomach of the anaesthetized rat from 0.34 to 4.10 mumol kg-1 i.v.). The results are consistent with the hypothesis that, at least in the ranitidine analogues, the "urea equivalent" moiety may be replaced by a polar group partially ionized at physiological pH without loss of H2-blocking activity. PMID- 2900600 TI - A symposium: Focus on heart failure--current experiences in basic research and clinical studies on dopexamine hydrochloride (Dopacard). September 12-13, 1987, Paris, France. Proceedings. PMID- 2900599 TI - Polyarteritis nodosa: an unusual cause of facial pain and swelling. PMID- 2900601 TI - The functional importance of beta 1 and beta 2 adrenoceptors in the human heart. AB - Radioligand binding studies have demonstrated convincingly the coexistence of beta 1 and beta 2 adrenoceptors in the human heart. Both subtypes are involved in the increase in tissue levels of cyclic adenosine monophosphate in isolated, electrically driven, human right atria and in the activation of adenylate cyclase in human cardiac membrane preparations. In isolated, electrically driven strips of human right atria, isoproterenol increased contractile force through stimulation of both beta 1 and beta 2 adrenoceptors, while the selective beta 2 adrenoceptor agonist, procaterol, caused its positive inotropic effect predominantly through beta 2-adrenoceptor stimulation. Norepinephrine, however, increased contractile force solely via beta 1-adrenoceptor stimulation. In this preparation, dobutamine also acted as a full agonist, producing a positive inotropic effect through stimulation of both beta-adrenoceptor subtypes. Dopexamine hydrochloride, on the other hand, having an approximately 10-fold greater affinity for right atrial beta 2 than for beta 1 adrenoceptors, acted as a partial agonist (maximal positive inotropic effect: about 30% that of isoproterenol). Similar effects have been obtained in human right and left ventricular strips; thus, there can be no doubt that cardiac beta 2 adrenoceptors can contribute to the positive inotropic effects of beta-adrenoceptor agonists in the human heart. Besides mediating positive inotropic effects, right atrial beta 2 adrenoceptors may be involved in the regulation of heart rate since, in healthy volunteers, the selective beta 2-adrenoceptor antagonist, ICI 118,551, was more potent than the selective beta 1-adrenoceptor antagonist, bisoprolol, in antagonizing isoproterenol-induced tachycardia, when both antagonists were administered in doses that selectively occupied more than 90% of beta 2 and beta 1 adrenoceptors, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900602 TI - An introduction to the pharmacologic properties of Dopacard (dopexamine hydrochloride). AB - Dopexamine hydrochloride (Dopacard) has been developed as a peripherally acting dopamine receptor agonist with afterload reducing properties for use in the acute management of low cardiac output states. Dopexamine hydrochloride is one-third as potent as dopamine in stimulating DA1 receptors but 60 times as potent as a beta 2-adrenoceptor agonist. Unlike dopamine, it is a weak beta 1-adrenoceptor agonist and does not stimulate vascular alpha adrenoceptors. Its stimulant properties at vascular DA1 receptors and at vascular beta 2 adrenoceptors endow it with the ability to improve renal blood flow and to increase cardiac output secondary to afterload reduction. In addition, mild positive inotropic activity arises from stimulation of cardiac beta 2 adrenoceptors, potentiation of endogenous norepinephrine due to uptake-1 blockade, and activation of the baroreceptor reflex. Other features of dopexamine hydrochloride that should enhance its clinical use are lack of arrhythmogenicity and rapid responsiveness to alterations in infusion rate. PMID- 2900603 TI - Antiarrhythmic strategies for the chronic management of supraventricular tachycardias. PMID- 2900604 TI - Spontaneous mutation in the male gamete as a cause of hemophilia A: clarification of a case using DNA probes. AB - The carrier status of two sisters of the mother of a hemophilic boy was clarified by the use of DNA probes in a family with a single case of hemophilia A and no family history of the disease. The extragenic polymorphic site demonstrated by probe DX13 (locus DXS15) and the intragenic polymorphic site demonstrated by BgI I digestion and a factor VIII partial cDNA probe indicated that the mother of the index case carried a mutation in the X-chromosome received from her nonhemophilic father rather than the X-chromosome received from her mother. In spite of equivocal coagulation data, the mother's two sisters were shown not to be carriers of hemophilia A. PMID- 2900605 TI - Synaptic behavior of myenteric neurons in guinea pig distal colon. AB - Intracellular recording methods were used in vitro to analyze the synaptic behavior of neurons in myenteric ganglia of guinea pig distal colon. Fast excitatory postsynaptic potentials (EPSPs) were observed in a variety of types of colonic neurons. Both spontaneous and stimulus-evoked EPSPs were abolished or suppressed by addition of hexamethonium, tetrodotoxin, or elevation of Mg2+ and reduction of Ca2+ in the bathing medium. Individual neurons usually received inputs from several fiber tracts and multiple EPSPs were sometimes evoked by electrical stimulation of single-fiber tracts. Stimulus-evoked fast EPSPs were always of greater amplitude, longer duration, and longer decay time than were spontaneous fast EPSPs in the same neurons. No rundown of the fast EPSPs occurred during prolonged stimulation at frequencies up to 10 Hz. Repetitive stimulation evoked slow depolarizing potentials (slow EPSPs) in 25% of the neurons. Characteristics of the slow EPSPs were 1) slow rise times, 2) duration in the seconds time domain, 3) enhanced excitability, 4) increased input resistance, and 5) reduction of hyperpolarizing after-potentials. In general, the variety of synaptic potentials and the properties of the events were the same as found in myenteric neurons of the guinea pig small bowel. Compared with synaptic behavior of small intestinal myenteric neurons, the notable differences were absence of the rundown phenomenon for fast EPSPs in the colonic neurons and a greater incidence of spontaneously occurring fast EPSPs. PMID- 2900606 TI - Mechanism of alpha 2-adrenoceptor agonist-induced diuresis. AB - In vivo and in vitro studies were performed to assess the mechanism of the diuretic effect of B-HT 933, a selective alpha 2-adrenoceptor agonist. In conscious Sprague-Dawley rats whose plasma vasopressin (AVP) levels were increased by infusion of hypertonic NaCl, B-HT 933 had no effect on AVP secretion. In Brattleboro homozygous (DI) rats, the antidiuretic dose response to AVP was shifted to the right by B-HT 933. In addition, a sustained antidiuresis induced in rats by infusion of 10 pg/min AVP was attenuated by B-HT 933 in a concentration-dependent manner. Pretreatment of DI rats with pertussis toxin (2 micrograms/kg iv) 4-5 days before testing abolished the inhibitory effect of B-HT 933 on AVP-induced antidiuresis. In outer medullary collecting ducts of DI rats, norepinephrine and B-HT 933 produced significant inhibition of AVP-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation. In contrast, the selective alpha 1-adrenoceptor agonist cirazoline had no effect on AVP-induced cAMP formation. The inhibitory effect of norepinephrine was antagonized by the selective alpha 2-adrenoceptor antagonist rauwolscine but not by prazosin, a selective alpha 1-antagonist. In outer medullary collecting ducts dissected from the pertussis toxin-treated DI rats used in the in vivo studies, the inhibitory effect of norepinephrine and B-HT 933 on AVP-stimulated cAMP accumulation was abolished. The results indicate that the hydrosmotic action of AVP is inhibited by alpha 2-agonists via a pertussis toxin-sensitive mechanism. PMID- 2900607 TI - Neural control of shark rectal gland. AB - Veratrum alkaloids stimulated salt secretion by the isolated perfused rectal gland of Squalus acanthias. Stimulation by veratrine was prevented by the nerve channel blockers tetrodotoxin and procaine and was not evident in a preparation of dispersed rectal gland cells. Vasoactive intestinal peptide (VIP)-like immunoreactivity was detected by histological techniques in neuronal tissue within the rectal gland. Veratrine stimulation caused the release of immunoreactive VIP into the venous effluent of perfused glands. The stimulatory action of veratrine was inhibited by somatostatin, another neuropeptide known to be present in nerves of Squalus rectal gland. These findings suggest the likelihood of neural modulation of rectal gland function. PMID- 2900608 TI - Recovery of neuromuscular function and postoperative morbidity following blockade by atracurium, alcuronium and vecuronium. AB - Recovery of neuromuscular function and postoperative morbidity were studied in 51 fit female patients who had nonemergency gynaecological laparoscopy as inpatients. They were allocated randomly to one of three groups to receive either atracurium 0.31 mg/kg, alcuronium 0.25 mg/kg, or vecuronium 0.06 mg/kg as part of an otherwise standard anaesthetic technique. There were neither differences in intubation conditions nor in the occurrence of postoperative diplopia whichever muscle relaxant was used. Deficits in grip strength and expiratory force were seen at one hour after reversal with atropine 1.2 mg and neostigmine 2.5 mg in all patients, deficits which persisted for 3 hours in those who received alcuronium. The recovery of inspiratory force was slower and less complete at up to 3 hours in those who received alcuronium and there was a high incidence of minor postoperative morbidity at up to 24 hours in each of the three groups. The only statistical difference in symptomatic morbidity was an increase in muscle weakness in those who received alcuronium compared with atracurium at 3 hours after laparoscopy. Only 25%, 20% and 31% of the patients who received atracurium, alcuronium and vecuronium respectively said that they would have liked to be day stay patients. PMID- 2900609 TI - Suxamethonium for penetrating eye injuries. PMID- 2900610 TI - The pharmacodynamics and pharmacokinetics of vecuronium in patients anesthetized with isoflurane with normal renal function or with renal failure. AB - The duration of action and the pharmacokinetics of vecuronium were compared in patients with and without renal function. Twenty patients were studied: 12 with renal failure who were to receive kidney transplants from cadaveric donors, and eight with normal renal function. After oral premedication with diazepam, 10 mg, anesthesia was induced with thiopental, 4 mg/kg iv, and maintained with the inhalation of 60% nitrous oxide and 0.9-1.1% isoflurane, end-tidal concentration, in 40% oxygen. The force of thumb adduction in response to supramaximal ulnar nerve stimulation was monitored and recorded. An intravenous bolus of vecuronium, 0.1 mg/kg, was administered after 15 min of a stable end-tidal isoflurane concentration, as measured by mass spectrometry. Venous blood was then sampled at frequent intervals for 4 h following the bolus. Vecuronium concentrations in plasma were quantified by a sensitive and specific gas chromatographic assay. Data were analyzed by nonlinear least squares regression and described by a two compartment model. The duration of neuromuscular blockade was longer in patients with renal failure than in those with normal renal function. This increased duration may be related to both a decreased plasma clearance and a prolonged elimination half-life of vecuronium in the renal failure group. PMID- 2900611 TI - The effect of two genes on anesthetic response in the nematode Caenorhabditis elegans. AB - The authors studied the wild type strain, N2, and three mutant strains of the nematode, Caenorhabditis elegans, in order to measure genetically produced changes in responses to nine volatile anesthetics. They determined the anesthetic ED50s of N2 for thiomethoxyflurane, methoxyflurane, chloroform, halothane, enflurane, isoflurane, fluroxene, flurothyl, and diethylether. The log-log relationship of the oil-gas partition coefficients (O/G) and the ED50s of these agents for N2 yields a straight line with a slope of -.997 with a R2 of .98 over a range of O/G (at 37 degrees C) from 48 to 7230. When the O/Gs are corrected to 22 degrees C, the slope is -.964 with an R2 of .98. This relationship is similar to that found in other animals. Two mutant strains, unc-79 and unc-80, show altered responses to these anesthetics. These strains are two to three times more sensitive than N2 to anesthetics with an O/G greater than that of halothane (220 at 37 degrees C), yet they differ little from N2 in response to anesthetics with lower O/Gs. unc-79 and unc-80 are about 30% more sensitive than N2 to diethylether. The double mutant unc-79; unc-80 is more sensitive to halothane, isoflurane, and fluroxene than is either mutant alone. The authors believe these data indicate an alteration at the site of action of volatile anesthetics in unc 79 and unc-80. They also postulate that the interaction of unc-79 and unc-80 indicate these genes code for enzymes in a common pathway, and that unc-79 precedes unc-80 in this pathway. PMID- 2900612 TI - Postoperative neuromuscular blockade: a comparison between atracurium, vecuronium, and pancuronium. PMID- 2900613 TI - [Effect of ganglionic blockaders on hemodynamics during eye surgery under local anesthesia]. PMID- 2900614 TI - Pressor responses from noncardioselective beta-blockers. AB - This study reviews more than fifty papers dealing with pressor responses from noncardioselective beta-blockers. It is concluded that the responses are usually mild. They occur mainly in situations of increased sympathetic activity. Therefore some patients seem to be at risk, eg, patients with unstable diabetes type 1, sportsmen performing isometric exercise, and heavy smokers. In orthostatic hypotension, noncardioselective beta-blockers may be beneficial. Cardiac output tends, however, to decrease, and patients with orthostatic hypotension will probably not benefit from this effect. PMID- 2900616 TI - Cystic fibrosis: recent advances in genetics and molecular biology. AB - Cystic fibrosis (CF) is the most common lethal hereditary disease of Caucasians, occurring once for every 2,000 live births. One out of 20 persons in the United States white population is a heterozygous carrier. An autosomal recessive pattern of inheritance is well established. The disease affects the respiratory and digestive tracts most severely. Despite the clearcut hereditary nature of the disease, insight into the biochemistry of CF has been almost totally lacking until very recently. New evidence strongly indicates that abnormal chloride ion transportation underlies the clinical manifestations. Recent advances in molecular genetics have established that the CF disease gene is located on the long arm of chromosome 7. Several restriction fragment length polymorphisms (RFLP) markers are closely linked to the CF gene. These markers permit antenatal testing of samples from fetuses at risk for CF with a high probability of disease prediction. One laboratory has isolated a desoxyribonucleic acid (DNA) sequence from chromosome 7 which is a candidate for the CF gene itself. A protein called the CF antigen is coded by a gene on chromosome 1. Patients with CF and carriers have abnormally high serum levels of this protein. In the normal state, the product of the CF gene on chromosome 7 may interact with the product of the gene on chromosome 1, enabling its normal catabolism and function. The structure of the CF antigen suggests that it may regulate ion transport. PMID- 2900615 TI - [How should a toxic accident be treated?]. AB - Local anaesthetic systemic toxicity is a rare but often dramatic complication of regional anaesthesia. Convulsions often follow warning signs, easily recognized when looked for; but they may occur from the first. They are rapidly followed by hypoxia and hypercapnia which greatly enhance the risk of severe cardiac depression, mainly with bupivacaine or etidocaine. Thiopentone is able to stop convulsions quickly, but may further depress the cardiovascular system. Diazepam has been shown to be effective in the treatment of local anaesthetic-induced convulsions. It gives less myocardial depression, but is much slower in effect. Midazolam, a new short-acting benzodiazepine, should be the best choice. Should tracheal intubation become necessary, suxamethonium can be used. Indeed, the principal use of these drugs is to make ventilation easier, so as to restore rapidly correct oxygenation. Severe cardiac depression, often leading to cardiac arrest, may occur from the first or after the appearance of convulsions. It generally follows a regional block carried out with bupivacaine. A few antiarrhythmic drugs have been used to treat ventricular arrhythmias, either in experimental studies (lidocaine, bretylium) or after clinical accidents (lidocaine). Their efficacy and innocuity have to be proved before they can be proposed to treat these accidents. Bradycardia only needs treatment with atropine when it causes severe haemodynamic disturbances. When cardiac arrest occurs, cardiopulmonary resuscitation must be carried out; its mainstays are: oxygen, sodium bicarbonate, adrenaline, calcium and perhaps glucagon. This must be continued for a long time, as late successes have been published. PMID- 2900618 TI - [Medullary cancer of the thyroid. Apropos of 20 years' experience in France]. AB - The majority (1013) of cases of medullary carcinoma of the thyroid observed in France in the last twenty years have been registered in a national file. Once overcome the difficulty of diagnosing the index case, all first degree parents at least should undergo a pentagastrin stimulation test and calcitonin estimation. Though such a policy involves difficulties of several types, it has resulted in the detection of 203 cases belonging to 61 families. 29 families suffered only from isolated MCT; in the 32 other families this cancer was a part of polyendocrinopathies of type 2a (28 cases) or type 2b (4 cases). The tumour was apparently of the sporadic type in 208 subjects. In 602 other cases the data were insufficient for a correct classification. An epidemiological enquiry of the disease is in progress since 1986. Though the number of complete files analysed is still insufficient, this study will be essential in understanding the natural history of the disease, the causes of its heterogeneity and in deducing eventually preventive measures even if in meantime a genetic marker is available. PMID- 2900617 TI - Effects of peroxidized polyunsaturated fatty acids on mitochondrial function and structure: pathogenetic implications for Reye's syndrome. AB - Linoleic acid, a polyunsaturated fatty acid, is a constituent of margosa oil which has been implicated as a cause of Reye's syndrome (RS) in infants. Increased concentrations of polyunsaturated fatty acids have been found in sera from patients with RS. Isolated rat liver mitochondria exposed to the peroxidized (but not unperoxidized) methyl esters of linoleic (C18:2) or linolenic (C18:3) acids showed decreases in state 3 and uncoupled respiratory rates and in respiratory control and ADP/O ratios. In addition, they caused mitochondrial swelling as demonstrated spectrophotometrically. Between the two, the peroxidized methyl ester of linolenic acid was more toxic and was capable of inducing high amplitude swelling ultrastructurally similar to that seen in the hepatocytes of RS victims. The ability of rat liver mitochondria to oxidize glutamate was inversely related to the peroxide concentration in the medium. This accords with the reports of reduced glutamic dehydrogenase activities in the livers of both patients with Reye's syndrome and rats treated with margosa oil. PMID- 2900619 TI - [Endocrine polyadenomatosis of 2a type (MEN 2a). Clinical and genetic study of a family]. AB - In a large kindred with multiple endocrine neoplasia type 2a (MEN 2a) (137 members, 5 generations), bilateral thyroid medullary carcinoma was found in all affected members. Pheochromocytoma was present in 59% of the cases, and was responsible at least for 4 out the 5 deaths related to MEN 2a. Hyperparathyroidism was less frequent (41%). Family screening leads to a reduction in age for diagnosis and to an improvement in the prevalence of complete healing after surgery. Linkage between HLA loci and a dominant gene for MEN 2a was investigated in this kindred. Lod scores for recombination fraction were all negative (-0.47 for a recombination fraction of 0.05). These results comfort the lack of linkage between MEN 2a and the HLA complex. PMID- 2900620 TI - [Tumor markers of medullary cancer of the thyroid body. Basic and endocrine aspects]. AB - MTC is characterized by multiple humoral and hormonal manifestations. Although calcitonin is the specific marker of the disease, somatostatin, the pro opiomelanocortin derived peptides and bombesin--among hormones produced by the tumor--can represent an exacerbation of normal C cells potentialities through genome derepression induced by the cancer. In this paper, the functional polymorphism of princeps tumoral markers and the endocrinological aspects of this neoplasia are reviewed. Molecular biology has been instrumental in discovering new tumoral peptides ("ancestral" CT forms, cryptic peptide and CGRP) and methods of CT detection; therefore, the role of CT could be better evaluated. In addition to its calciotropic role, CT acts also as a neuromodulator on some hypophyseal hormones. Conversely, CT secretion is also regulated by amines and neuropeptides, providing the basis of potential hormonal treatment. PMID- 2900621 TI - [The genetics of medullary cancer of the thyroid]. AB - 10% of patients with medullary thyroid carcinoma have a family history of this cancer. The genetic nature is much more marked in the associations known by the name of multiple endocrine neoplasms (MEN) type II. Type IIa is compatible with autosomal dominant inheritance. The clinical symptoms may be revealed later, but the response of calcitonin to pentagastrin should allow the diagnosis of all carriers of the gene before the age of 35 years. The incomplete nature of clinical penetrance (probably 80%) may lead to errors of omission in the screening. The disease appears to be less aggressive in certain lines, without any explanation at the present time. The locus of MEN is probably on chromosome 10, in the centromere region or nearby on the long arm. The mechanism of tumourigenesis has not yet been elucidated. Hopefully, in the near future, reliable markers for the identification of children at risk will be available together with an understanding of the genetic heterogeneity of the disease. PMID- 2900622 TI - Somatostatin and neuropeptide Y concentrations in pathologically graded cases of Huntington's disease. AB - Somatostatin and neuropeptide Y concentrations have previously been reported to be increased in the basal ganglia in Huntington's disease (HD). In the present study we have extended these findings by examining both somatostatin-like immunoreactivity (SLI) and neuropeptide Y-like immunoreactivity (NPYLI) in cases of HD, which were graded according to the severity of pathological degeneration in the striatum. In addition, we surveyed a large number of subcortical nuclei and cortical regions for alterations. Both SLI and NPYLI were significantly increased about threefold in the caudate, putamen, and the nucleus accumbens. Increases in mild and severe grades were similar, which is consistent with a relative but not absolute sparing of striatal aspiny neurons in which somatostatin and neuropeptide Y are colocalized. Significant increases of NPYLI were also found in the external pallidum, subthalamic nucleus, substantia nigra compacta, claustrum, anterior and dorsomedial thalamus, bed nucleus of the stria terminalis, and locus ceruleus. SLI was significantly increased in the external pallidum, red nucleus, and locus ceruleus. Measurements of both neuropeptides were made in 24 regions of the cerebral cortex. Significant increases in both NPYLI and SLI were found in the frontal cortex (Brodmann areas 6, 8, 9, 10, 11, and 45) and temporal cortex (Brodmann area 21), whereas NPYLI was also increased in Brodmann areas 12, 20-22, 25, and 42. Alterations in the cerebral cortex were as pronounced in cases with mild striatal pathological changes as in those with severe striatal pathological changes. These alterations may occur early in HD and could reflect a selective sparing of somatostatin-neuropeptide Y cortical neurons combined with cortical atrophy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900623 TI - DNA and protein polymorphism: application to anthropology and human genetics. AB - In this paper, the author analyses the different approaches of the DNA polymorphism. Mitochondrial DNA, RFLP haplotypes associated with serum protein polymorphism, variability of some small regions of the genome detected by minisatellite probes are now well developed and often adapted to population analysis. The data gathered are used to build phylogenic or genealogic trees. Despite the limited number sampled in these investigations, it is obvious that they were obtained to establish a beginning of geographical map distribution of the DNA polymorphisms and to answer basic questions in Anthropology. In this sense, DNA polymorphism is a new way to obtain a large amount of information not available through the different polymorphisms previously performed. Today, the interpretation of the data on DNA polymorphism is based on archeological and prehistorical hypotheses. It is highly probable that for a long time, no phylogenic analysis will be able to determine the step of speciation, the period of emergence of primitive man and of his geographical origins. In some fields of anthropological investigations, studies on the DNA structure and organisation may bring new information on the genetic of skin pigmentation, eye and hair colours, body size, etc. But the essential aim of studies on humans cannot exist out of multidisciplinary follow up including sociology, biology, linguistics, behaviour and economy. Molecular biology of DNA is an additional method from which we can learn a lot about human genetic heterogeneity but man is a group, a society, a population, a tribe and not a certain amount of allele frequencies. PMID- 2900624 TI - Treatment of severe psoriasis with somatostatin: four years of experience. AB - Over a period of 4 years, 20 patients suffering from severe forms of psoriasis (erythrodermic, sub-erythrodermic, resistant generalized forms and/or forms associated with acute arthropathy) were treated with 96 h of continuous i.v. infusion of somatostatin (Stilamin, Serono) diluted in D5W at 250 micrograms/h. In addition to the usual blood chemistry parameters, circadian levels of growth hormone (GH) and epidermal growth factor (EGF) were measured before, during, and after therapy. Approximately 2-3 weeks after termination of therapy, erythrodermic and suberythrodermic symptoms had disappeared. In some patients, a few lesions of psoriasis vulgaris remained, although they were much less severe. Remission of acute arthropathy was impressive. Blood chemistry parameters were unchanged after therapy. Circadian levels of GH and EGF, normal before therapy, were significantly decreased after therapy. The infusion was well-tolerated. Infusion rates of greater than 250 micrograms/h caused only some complaints of abdominal pain, nausea, and vomiting. During the 4 years, erythrodermic symptoms reappeared only in seven patients, three of whom were also arthropathic. After 6 8 months, they underwent a second course of somatostatin therapy with good results. The other patients are still able to control their disease with tar based products alone or with low-dose 8-methoxypsoralen + UVA (PUVA) or UV therapy. The arthropathic patients control their symptoms with periodic low-dose nonsteroidal antiinflammatory drug therapy. PMID- 2900625 TI - [Congenital heart diseases and urinary malformations]. AB - The purpose of this study was to evaluate the advisability of a systematic search for uropathy in patients with malformative heart disease. Thirty-three cases of urinary tract malformation associated with congenital cardiopathy are reported. These cases represent 2.8 p. 100 of all cardiac patients seen during the same period. The congenital heart diseases were varied, with a predominance of ventricular septal defect (48 p. 100) followed by dextrocardia, single ventricle and coarctation of the aorta. UT abnormalities included vesico-ureteral reflux (36 p. 100), renal agenesis (5 cases), renal dysplasia or hypoplasia (4 cases), upper UT obstruction (4 cases), hypospadias (3 cases), renal ectopia (3 cases), lower UT obstruction (2 cases), polycystic kidney, megaloureter, horseshoe kidney and supernumerary kidney (1 case each). A study of the literature showed that the two uropathies with a risk of associated cardiopathy are renal agenesis and horseshoe kidney. The cardiopathy-uropathy association was found in isolation (11 cases) or combined with cryptorchidism (2 cases) or with multiple malformations (20 cases). The malformations were diverse, the most frequent being neurosensorial malformations (70 p. 100), followed by skeletal malformations (55 p. 100) equally divided between apine and limbs, genital malformations (35 p. 100) and digestive tract malformations (25 p. 100). A study of the cardiopathy uropathy concordances failed to elicit any predominant association; in the literature, ventricular septal defect is usually associated with horseshoe kidney.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900626 TI - [Postnatal development of somatostatin neurons in the rabbit visual cortex. Quantitative and morphological study]. PMID- 2900627 TI - Beta-blocker effects on sexual function in normal males. AB - Among the antihypertensives currently in use, the sympatholytic drugs (e.g., central alpha-agonists, beta-blockers) and diuretics are most commonly associated with sexual side effects. Previous reports of sexual dysfunction associated with these drugs have been based entirely on retrospective and self-report data. This is the first study to date to investigate beta-blocker effects on sexual function by means of physiological (NPT), subjective, and hormonal measures. Four beta blockers with different ancillary properties (atenolol, metoprolol, pindolol, propranolol) were evaluated in a placebo-controlled, double-blind, Latin-square design. Thirty healthy male volunteers received, in counterbalanced order, each of the four drugs and 1 week of placebo testing. Significant drug effects on both total and free testosterone were found during treatment with all four beta blockers, although it appeared that the nonselective drugs (pindolol, propranolol) were associated with the greatest reduction in testosterone. No significant effects were found on measures of cortisol or cholesterol. Analysis of NPT and self-report data yielded inconclusive results, perhaps due to the confounding effects of sleep disruption and the brief duration of treatment in this study. Inspection of individual records, however, suggested that some subjects may be especially vulnerable to sexual dysfunction in association with propranolol. PMID- 2900628 TI - [The morphology of amebiasis]. AB - Amebiasis--a protozoan human disease caused by Entamoeba histolytica--occurs in the USSR sporadically in particular geographic regions and in particular populations. The paper reports morphologic findings made in patients with amebiasis involving the intestine or other organs. In typical cases, amebiasis affects the large intestine, particularly the cecum and ascending colon, and has the development of distinctive ulcers as its characteristic feature. As the disease progresses, these appear in all parts of the large intestine; less commonly, the terminal portion of the small intestine is also involved. The most frequent complications of amebic colitis are perforation and phlegmon, which result in peritonitis. Not infrequently, amebic abscesses arise in the liver or other organs through hematogenous dissemination of amebas. Histologic diagnosis of amebiasis may be difficult. Recommendations on how to detect amebas and the tissue changes peculiar to amebiasis are given. PMID- 2900629 TI - [Preventive effects of L-alanine and L-glutamic acid on acute toxicity of acetaldehyde in mice]. PMID- 2900630 TI - HLA B27 positive helicopter pilot with reactive arthritis responsive to sulfasalazine. AB - An aviator with prolonged right sided low back pain is described. The diagnostic workup is presented leading to diagnosis of HLA B27 positive reactive sacroiliitis. Trial of sulfasalazine lead to resolution of his pain. The spondylarthropathies are briefly reviewed. Implications on his aeromedical status are discussed. PMID- 2900631 TI - Inherited forms of rickets and osteomalacia. PMID- 2900632 TI - Synthesis of human factor XIIIa in bacterial cells. AB - The coding sequence for human factor XIIIa (FXIIIa) was introduced into Escherichia coli expression vectors. Bacterial cells transformed with the recombinant plasmids synthesized fusion proteins of the expected molecular weights and the proteins were shown to be immunoreactive with anti-FXIII antibodies. Furthermore, with the help of oligodeoxynucleotide synthesis, we constructed a plasmid which directs the synthesis of the human FXIIIa protein in the unfused form. Sequence determination at the aminoterminus of this protein revealed the identical sequence compared to placental FXIIIa. The protein is expressed intracellularly in a denatured and biologically inactive form. It constitutes approximately 2% of total cellular protein and can easily be purified by standard methods. PMID- 2900633 TI - Panic, fear reduction and habituation. PMID- 2900635 TI - In vitro translation and processing of human hepatoma cell (Hep G2) gamma glutamyl transpeptidase. AB - Human hepatoma cell (Hep G2) gamma-glutamyl transpeptidase (gamma-GT), a 120 ka single-chain glycoprotein, is much larger than the expected precursor of the dimeric enzyme in other human tissues. However, the Hep G2 gamma-GT mRNA encodes a 63 kDa peptide, similar to that of rat gamma-GT mRNA product and to the predicted, unglycosylated precursor of the enzyme in human tissues. Translation in presence of dog pancreas microsomes results in processing of the 63 kDa to an 80 kDa core-glycosylated species which is subsequently cleaved to 58 and 22 kDa subunits resembling those in other human tissues. The unusually large Mr of gamma GT in Hep G2 would thus seem to be due to further glycosylation and processing in the Golgi. A deficiency of the processing protease is the most likely reason for the persistence of the single-chain form of gamma-GT in Hep G2 cells. PMID- 2900636 TI - Evidence for a FSH dependent secretion of a receptor reactive transforming growth factor beta-like material by immature Sertoli cells in primary culture. AB - Type beta Transforming Growth Factor (TGF beta)-like activity was identified in conditioned medium obtained from immature porcine Sertoli cell-enriched cultures using the following criteria: (i) stimulation of anchorage independent growth of mesenchymal cell lines, (ii) competition with pure human TGF beta in a radioreceptor assay. The secretion of the receptor reactive TGF beta-like material in Sertoli cell conditioned medium is decreased to very low or undetectable levels by Follicle Stimulating Hormone, one of the major hormones involved in the physiological testicular activities. The effects of this factor are probably exerted in the context of the local control of the male gonad functions. PMID- 2900634 TI - Identification of the junction between the glutamine amidotransferase and carbamyl phosphate synthetase domains of the mammalian CAD protein. AB - The hamster CAD gene encodes a protein that catalyzes the first three steps of pyrimidine biosynthesis. We have sequenced a portion of a CAD cDNA and determined the location of the carbamyl phosphate synthetase II coding region. Subdomains coding for the glutamine hydrolyzing and carbamyl phosphate synthesizing functions have been identified through their high degree of similarity to carbamyl phosphate synthetase genes from a variety of organisms. The proline-rich junction between the glutaminase and synthetase domains, however, does not appear to be conserved among carbamyl phosphate synthetases. PMID- 2900637 TI - Tightly bound 2-azido-adenine nucleotides at catalytic and noncatalytic sites of the rat liver F1 ATPase label adjacent tryptic peptides of the beta subunit. AB - UV irradiation of rat liver F1 ATPase, previously exposed to Mg2+ and [beta, gamma-32P]-2-azido-ATP and separated from medium nucleotides, covalently modifies two tyrosine residues in adjacent tryptic peptides of the beta subunit. This results from the occupancy by 2-azido-ATP or 2-azido-ADP of two distinct types of nucleotide binding sites, the catalytic and noncatalytic sites. The two modified peptides are identical to the ones modified by 2-azido-adenine nucleotides in the beef heart F1 ATPase. Both catalytic and noncatalytic sites are labeled when the ATPase is exposed to [beta-32P]-2-azido-ADP in the presence or the absence of 5' adenylyimidodiphosphate (AMP-PNP), showing that two distinct types of ADP binding sites are present on the liver enzyme. Similar incorporation of 2-azido-adenine nucleotides is obtained when membrane-bound rat liver F1 ATPase is incubated with Mg2+ and [beta, gamma-32P]-2-azido-ATP. PMID- 2900638 TI - Adenine nucleotides regulate the functional transition in mitochondrial H+-ATPase and the kinetic behaviour of its ATP-synthetase form. AB - The kinetics of the SMP-catalyzed Pi-ATP exchange and oxidative phosphorylation was studied at variable [MgATP] + + [MgADP] and [MgATP]/[MgADP]. The existence on F1 of a center with a low affinity was demonstrated (KM = 0.4-2.7 mM). Saturation of this center with the Mg2+-complex of one of the nucleotides is obligatory for H+-ATPase to exhibit its ATP synthetase activity. It was found that with a decrease of [MgATP]/[MgADP] the lag periods, tau, of the reactions and KM(Pi) also show a decrease. Besides, in the Pi-ATP exchange reactions delta microH+ (steady-state) diminishes and SMP coupling is enhanced (the Vhydr/Vsynth ratio is decreased). Preincubation of SMP with MgADP eliminates the lags but does not affect the course of the steady-state reaction. It is concluded that F1 when bound to MgATP or MgADP changes to a "more" or "less coupled" conformational state, thus determining the rate of conversion to the ATP-synthetase functional state (ko = tau-1), the threshold potential of this conversion and the kinetic behaviour of ATP-synthetase (KM for Pi). PMID- 2900639 TI - Acromegalic arthropathy. Characteristics and response to therapy. AB - Arthropathy was assessed in 19 patients with active acromegaly. Axial or peripheral arthropathy was present in 10 patients, was located most often in large joints or the lumbosacral spine, and was osteoarthritic in nature. The mean duration of acromegaly in patients with arthropathy was 21.6 years, while the mean duration in patients without arthropathy was 7.9 years. A mild-to-moderate improvement in symptoms, estimated functional ability, and crepitus occurred in 8 of 9 patients who were prospectively examined during therapy to lower production of growth hormone. We conclude that this therapy did improve the symptoms of acromegalic arthropathy. Whether objective structural improvements occur remains unclear. PMID- 2900640 TI - Adult T cell leukemia presenting with proliferative synovitis. PMID- 2900641 TI - [General review of a non-sedative antihistaminic, astemizole (Hismanal), a H1 receptor antagonist]. AB - The non-sedating antihistamine Astemizole seems to approach all the major characteristics of the ideal histamine H1 antagonist, according to a comprehensive review of 54 clinical trials and clinical use in over 6,500,000 patients worldwide. The following statements concerning Astemizole can now be made: Astemizole is more potent than any other known antihistamine, following Astemizole therapy, H1 blockade is complete in the main target tissues, such as nasal and ocular mucosa, this blockade is also specific, since all histamine mediated signs and symptoms respond to the drug, this blockade is maintained, since tolerance does not appear during long-term treatment. Astemizole is a non sedative and non-toxic drug, even during chronic use. Astemizole is very effective in patients with chronic urticaria. Astemizole has well-documented beneficial protective effects on histamine-induced bronchoconstriction. PMID- 2900642 TI - Taxol-induced reorganization of the microtubule system in murine splenic lymphocytes inhibits response to allogeneic cells but not to concanavalin A. AB - The exposure of mouse splenic lymphocytes to the microtubule assembly-promoting drug taxol (10 microM for 4 h) results in an extensive reorganization of the microtubule system to form one to a few large bundles of microtubules, which extend from the centrosome. Lymphocytes pretreated with taxol for 4 h, or cultured in the continued presence of taxol, respond normally to the mitogen concanavalin A up to, and including, the stage of DNA replication. In contrast, the induction of DNA synthesis during the alloactivation of lymphocytes is inhibited when taxol is present in the mixed leukocyte culture. If the stimulators are pretreated with this drug, the mixed leukocyte reaction occurs normally, but pretreatment of the responders inhibits the proliferative response markedly. Microscopic observations of nuclear morphologies in these populations and autoradiography indicate that taxol inhibition occurs early in alloactivation, prior to DNA replication. The responding ability of taxol-treated lymphocytes is not restored to control levels by the addition of interleukin 2, leading to the suggestion that interleukin 2 receptors do not emerge or function normally in these cells. We conclude that the capacity to respond to allogeneic cells, but not to a mitogen, is dependent on the presence of the normal submembranous organization of the microtubule system. PMID- 2900643 TI - Normal and anomalous structures simulating retroperitoneal lymphadenopathy at computed tomography. AB - The present report illustrates normal and anomalous anatomic structures which may represent pitfalls in diagnosis when computed tomography of the abdomen is performed in the search for enlarged retroperitoneal lymph nodes. PMID- 2900644 TI - Failure of dopexamine to maintain haemodynamic improvement in patients with chronic heart failure. AB - Ten patients with chronic heart failure were given a continuous infusion of dopexamine after an initial stage of dose titration. On the dose selected the cardiac index initially rose by 56%, as a result of an increase in both heart rate and stroke volume index. Systemic vascular resistance fell by 34% and the mean arterial pressure did not change. Within 18 hours of the start of the continuous infusion, however, all the variables except heart rate had returned to preinfusion values. Nine of the 10 patients were withdrawn from the 48 hour study, six because of haemodynamic deterioration and two because of side effects. If the premature loss of therapeutic effect reflects an intrinsic property of this agent, dopexamine may be of limited clinical value. PMID- 2900645 TI - Myocardial ischaemia: progress in drug therapy. PMID- 2900646 TI - Cyclophosphamide and tamoxifen as adjuvant therapies in the management of breast cancer. CRC Adjuvant Breast Trial Working Party. AB - In 1980 the Cancer Research Campaign launched a multi-centre breast cancer trial; aimed at repeating the Scandinavian Chemotherapy Study Group's cyclophosphamide trial, and the NATO tamoxifen study; thereby further evaluating the role of these two adjuvant regimens in patients with early breast cancer. Two thousand two hundred and thirty women were randomized into this trial between 1980 and 1985 and preliminary analyses demonstrate a significant improvement in event-free survival for both regimens. Results from this study closely parallel the two trials it set out to repeat. PMID- 2900647 TI - Controlled trial of tamoxifen as a single adjuvant agent in the management of early breast cancer. 'Nolvadex' Adjuvant Trial Organisation. AB - At a maximum follow up of 8 years (median 5 years 6 months) in a randomised trial of adjuvant tamoxifen versus no treatment as therapy for early breast cancer, a significant advantage persists for patients receiving 20 mg of tamoxifen daily for 2 years. This advantage is independent of menopausal status, stage, grade and ER status. Log hazard rate analysis fails to demonstrate a rebound effect on stopping the drug and suggests that more prolonged treatment might further improve results. PMID- 2900648 TI - Treatment of chronic urticaria with cetirizine dihydrochloride a non-sedating antihistamine. AB - The efficacy of cetirizine dihydrochloride, a new H1-antagonist with minimal sedative or anticholinergic side effects was evaluated in 30 patients with chronic idiopathic urticaria. In the first part of the study, cetirizine 10 mg and placebo were compared in a double-blind cross-over trial. In the second part, patients who did not respond adequately in the first part were randomized, still double-blind, to receive 10 mg cetirizine either once daily or twice daily. In the first part, treatment was discontinued by 17 patients on placebo and two patients on cetirizine because of lack of efficacy. Cetirizine dihydrochloride was found significantly to reduce occurrence of weals, erythema and pruritus compared with placebo (P less than 0.001). Twenty-six of the patients improved on cetirizine and two on placebo. Mild sedation was noted by two patients on cetirizine and by one on placebo. PMID- 2900649 TI - Transplantation of embryonic haemopoietic stem cells without prior recipient X irradiation. AB - Allogeneic day 7 mouse embryonic cells can colonize the haemopoietic system of normal, non-irradiated recipient mice. Donor embryonic cells are disaggregated and injected intravenously resulting in colonization in 40% of recipients, as shown by the presence of electrophoretic markers, characteristic of the donor cells. Donor type haemoglobin (Hb) and donor type glucose phosphate isomerase (GPI) demonstrates the presence of donor type erythrocytes and lymphocytes respectively. Repeat grafts in recipients not showing donor makers did not result in colonization. Recipient type haemopoiesis was dominant in all types of recipient. Skin grafts of allogenic donor type skin onto successfully grafted embryonic cell recipients did not survive. Allogeneic donor embryonic cells therefore survive in recipients where adult skin allografts do not. Donor embryonic cells, homozygous for T6 marker chromosomes, were used to assess the site of colonization of intravenously grafted cells. Donor chromosomes were seen in recipient liver and bone marrow at low levels. This distribution of donor cells persists for up to 64 d post-graft. PMID- 2900650 TI - Effects of the beta-agonist, cimaterol, on growth, body composition and energy expenditure in rats. AB - 1. Male Sprague-Dawley rats weighing 146.5 (SE 4.3) g were fed on a semi synthetic diet containing 0, 25 or 150 mg cimaterol/kg for 12 d. Net changes in weight and composition of carcass, liver, heart, gastrointestinal tract, gastrocnemius plus plantaris muscles, skin and remainder were estimated by comparative slaughter. 2. Cimaterol increased protein gains in gastrocnemius plus plantaris muscles from 0.09 g in controls to 0.14 and 0.12 g in 25 and 150 mg cimaterol/kg groups respectively. Carcass protein gains increased from 6.27 g in controls to 8.00 and 7.05 g in 25 and 150 mg cimaterol/kg groups respectively. 3. Rats treated with cimaterol either gained less fat or actually lost fat from all tissues studied, whilst control rats gained fat. These changes were reflected in lower energy retention in cimaterol-fed rats. 4. Energy intake was not affected by treatment. Cimaterol increased heat production from 776 kJ/kg body-weight0.75 in controls to 863 kJ/kg body-weight0.75 in both treated groups. Gross efficiency was reduced from 17.4% in controls to 8.0 and 7.7% in rats fed on 25 and 150 mg cimaterol/kg diets respectively. 5. These results indicate that cimaterol increases protein gain at the expense of fat in rats. In addition, subcutaneous adipose tissue appears to be more sensitive than abdominal fat, whilst protein gains are particularly enhanced in skeletal muscle relative to other body tissues. PMID- 2900651 TI - Multiple sites and synergism in the binding of inhibitors to microsomal aminopeptidase. AB - The active site of microsomal aminopeptidase has been probed by studying the inhibition of the enzyme in the simultaneous presence of two ligands. The results have been analyzed with the Yonetani-Theorell plot to quantitate the degree of interaction between the two inhibitors. As expected, the enzyme contains a strong binding site for the alpha-amino group and the hydrophobic side chain of specific substrates. In addition, however, the enzyme can interact with another amine and a second hydrophobic group. Evidence suggests that this extra amine may bind to the zinc in an unprotonated form and that one of the hydrophobic sites is located in the vicinity. Another unexpected finding in this work is a strong synergism between the binding of ammonia and that of zinc ligands such as hydroxamates. This synergism may reflect an induced-fit mechanism that brings the catalytically important zinc atom into the optimal state only in the presence of specific substrates. PMID- 2900652 TI - Function of tightly bound nucleotides on membrane-bound chloroplast coupling factor. AB - The kinetic behavior of tightly bound nucleotides on chloroplast coupling factor from spinach was determined under phosphorylating and nonphosphorylating conditions. Chloroplast coupling factor 1 (CF1) was labeled with tightly bound radioactive ADP and/or ATP at two specific sites and reconstituted with thylakoid membranes depleted of CF1 by treatment with NaBr. The initial incorporation and dissociation of ADP from one of the sites requires light but occurs at the same rate under phosphorylating and non-phosphorylating conditions. The initial rate is considerably slower than the rate of ATP synthesis, but nucleotide exchange is very rapid during steady-state ATP synthesis. A direct correspondence between this nucleotide binding site and a site on soluble CF1 that hydrolyzes ATP was demonstrated. A second site binds MgATP very tightly; the MgATP does not dissociate during ATP synthesis nor does its presence alter the rate of ATP synthesis. This is analogous to the behavior found for soluble CF1 during ATP hydrolysis. These results demonstrate that the tight-binding nucleotide sites on soluble CF1 and membrane-bound coupling factor are essentially identical in terms of binding properties and kinetic behavior during ATP hydrolysis and synthesis. PMID- 2900653 TI - Uncoupling protein in embryonic brown adipose tissue--existence of nonthermogenic and thermogenic mitochondria. AB - Embryonic development of mouse and rat brown adipose tissue was characterized by electron microscopy and by quantifying the mitochondrial oxidative, phosphorylating and thermogenic capacities immunochemically, using antibodies against cytochrome oxidase, F1-ATPase and uncoupling protein, respectively. Mitochondria and cytochrome oxidase were detected from the 15-16th day of pregnancy and their amounts continuously increased toward birth. F1-ATPase was also found on the 15th day but it reached a maximum level already on the 19th day when the uncoupling protein appeared and rapidly increased during further maturation of brown adipose tissue. It thus appears that mitochondria in early prenatal brown adipose tissue lack completely uncoupling protein and are nonthermogenic. They transform into typical thermogenic mitochondria abruptly only 2 days before birth. PMID- 2900654 TI - Protection of tyrosine aminotransferase against proteolytic digestion by nucleotide derivatives. AB - The abilities of several nucleotides to protect tyrosine aminotransferase (L tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) against proteolytic inactivation in vitro have been examined as part of an ongoing investigation of the role of cyclic GMP in the intracellular degradation of the hepatic enzyme. Although neither cyclic GMP nor cyclic AMP was found to exert such a protective effect, certain nucleotide analogs were observed to inhibit the inactivation of tyrosine aminotransferase by trypsin and chymotrypsin. The nucleotides which conferred the strongest protection were the dibutyryl derivatives of cyclic GMP and cyclic AMP. This phenomenon appears to require a purine nucleotide with hydrophobic substituent(s), while the cyclic phosphate is not essential. The nucleotides probably act by direct interaction with tyrosine aminotransferase as indicated by changes in kinetic properties and heat stability of the enzyme and by their failure to inhibit trypsin when other protein substrates, including another aminotransferase, were used. Dibutyryl cyclic AMP was shown to block the appearance of a characteristic 43 kDa tryptic cleavage product of tyrosine aminotransferase but not the conversion of the native 54 kDa form to a size of 50 kDa. Arguments are presented against the involvement of the protective effect in the actions of dibutyryl cyclic nucleotides on tyrosine aminotransferase in cells. PMID- 2900655 TI - Extracellular cAMP formation from host cell ATP by Bordetella pertussis adenylate cyclase. AB - The effect of exogenously added adenylate cyclase from Bordetella pertussis (strain 114) has been investigated in Y-1 mouse adrenal tumor, chinese hamster ovary (CHO) and several other cells. A partially purified adenylate cyclase was found not to enter cells but, nevertheless, produced large amounts of cAMP in the medium. We could show that this resulted from release of ATP (and not larger molecules). The ATP released by the cells could be (1) directly measured and was replenished after each change of medium; (2) was reciprocally related to the cAMP produced; and (3) was competed for by ATPases present in added serum or by hexokinase and, less effectively, by exoenzymes on the cell surface. The extent of ATP leakage varied widely between different cell lines, being marked in CHO and Y-1 adrenal cells but negligible in transformed lymphocyte lines. The uncertainty of the origin of cAMP found in media of cultured cells requires separate analysis of cell and medium cAMP and an assessment of ATP leakage. PMID- 2900656 TI - TRH test and DST in schizoaffective mania, mania, and schizophrenia. AB - The thyrotropin-releasing hormone (TRH) test and the Dexamethasone Suppression Test (DST) were given to 10 patients who met Research Diagnostic Criteria (RDC) for schizoaffective disorder, manic type, 9 who met the criteria for mania, and 27 who met the criteria for schizophrenia. A blunted thyrotropin (TSH) response to TRH was observed in 3 of the 10 schizoaffective manics, 4 of the 9 manics, and 3 of the 27 schizophrenics. Nonsuppression on the DST was observed in 5 of the 10 schizoaffective manics, 2 of the 9 manics, and 2 of 22 schizophrenics. The schizoaffective manic and the manic patients had similar rates of TSH blunting and DST nonsuppression, and these were significantly higher than the rates in the schizophrenic patients. This difference was not attributable to baseline TSH and cortisol levels or to neuroleptic treatment. It is suggested that patients with RDC schizoaffective mania and mania have more disturbance in the hypothalamic pituitary adrenal and thyroid axes than patients with schizophrenia. PMID- 2900657 TI - Gamma-glutamyl transpeptidase, glutathione, and L-glutamic acid in the rat epididymis during postnatal development. AB - During postnatal development, gamma-glutamyl transpeptidase (gamma-GT), reduced glutathione (GSH), and L-glutamic acid (L-Glu) were assayed in the epididymides of rats at 5-day intervals between 10 and 60 days of age and compared to adult levels. gamma-GT activity (with gamma-glutamyl-p-nitroanilide as substrate) and L Glu (nicotinamide adenine dinucleotide conversion-dependent assay) were measured photometrically, while GSH (o-phthalaldehyde reaction) was quantified with a fluorometric assay. In immature rats, the epididymal gamma-GT was very low but increased after 25 days of age in the caput and after 50 days of age in the cauda. The enzyme level in the epididymal caput was by far the highest in the adult rat reproductive tissues. The postnatal increase of gamma-GT in epididymal caput and cauda was associated with a decline of its substrate GSH and an accumulation of the product L-Glu. These observations provide evidence for the in vivo hydrolytic activity of gamma-GT and explain the high levels of L-Glu found in the epididymis of rats and other mammals. PMID- 2900658 TI - Classification and treatment of systemic vasculitis. PMID- 2900660 TI - Quantitative correlation between tetanus-induced decreases in extracellular calcium and LTP. AB - Decreases in the extracellular calcium concentration ([Ca2+]o), induced by tetanization of the Schaffer collaterals in rat hippocampal slices, were measured by means of Ca2+-sensitive microelectrodes. The amount of long term potentiation (LTP) of the evoked field potentials, induced by this tetanus, was determined. A positive correlation was found between the amplitude of the tetanus induced decrease in [Ca2+]o and the amount of LTP that was elicited. The N-methyl-D aspartate (NMDA) receptor antagonist 2-amino-phosphonovalerate decreased both the tetanus-induced decreases in [Ca2+]o and the amount of LTP that was induced. We conclude that the amount of Ca2+ that enters the cell during a tetanus is of major importance in the induction process of LTP. PMID- 2900659 TI - Clinical findings and prognosis of polyarteritis nodosa and Churg-Strauss angiitis: a study in 165 patients. AB - Factors influencing the prognosis were studied in 165 patients with polyarteritis nodosa (PAN) and Churg-Strauss angiitis. One hundred and forty-seven of the patients fulfilled histological and/or arteriographic diagnostic criteria, and in 18 patients the diagnosis was based on clinical criteria. The patients' mean age on diagnosis was 48.4 +/- 16.4 years. The main symptoms were fever (69%), weight loss (66%), arthritis (44%), mononeuritis multiplex (67%), cutaneous signs (46%), renal involvement (26%), gastrointestinal symptoms (31%), asthma (29%), hypertension (31%) and cardiac failure (18%). Ninety-two per cent of the patients survived for at least 1 year after diagnosis of the disease, 79% for 2 years, and 63% for 5 years. The immediate causes of death were gastrointestinal bleeding or peritonitis in 11 cases, pancreatitis in two, renal insufficiency in six, cardiac failure in five, infectious complications in four, stroke in three and other causes in 11. We studied the prognosis of necrotizing angiitis in relation to clinical symptoms and laboratory findings. The association of four conditions were associated with a poor prognosis: age over 50, gastrointestinal problems, cardiomyopathy and renal signs. The survival rates in patients with these conditions were: for gastrointestinal problems, 55% 5-year survival (versus 67%); and for age over 50, 68% 3-year survival (versus 78%; p less than 0.09). One hundred and fifty-nine patients were treated with steroids for at least 18 months. Forty-eight also received cytotoxic agents (27%) and 46 plasma exchange. Patients who were treated with plasma exchange and prednisone were randomly assigned to additional treatment with cyclophosphamide. Survival rates were comparable in both groups. PMID- 2900661 TI - Electrophysiological properties of paraventriculo-spinal neurones in the rat. AB - In rats anaesthetized with urethane, electrical stimulation of the thoracic cord at T9-10 evoked antidromic response in neurones in the parvocellular portion of the ipsilateral paraventricular nucleus. Estimated conduction velocities in the spinally-projecting axons ranged from 0.6-5.9 m/sec. The majority (97%) of spinally projecting neurones were quiescent. Increases or decreases in the level of baroreceptor stimulation produced by intravenous injection of phenylephrine (1 5 micrograms) or sodium nitroprusside (10-15 micrograms) inhibited and excited amino acid-induced activity in 5/8 and 4/11 neurones respectively. Stimulation of vagal afferent endings by rapid bolus injection of 5-HT, to evoke the Bezold Jarisch reflex. inhibited amino acid-induced activity in 15/18 cells. Activation of gastric vagal afferents by distension of the stomach had no effect on paraventriculo-spinal cells. It is suggested that at rest the excitability of paraventriculo-spinal neurones is depressed by a tonic inhibitory input which arises from vagal afferent fibres in the heart. PMID- 2900662 TI - Age-related decrements in the muscarinic enhancement of K+-evoked release of endogenous striatal dopamine: an indicator of altered cholinergic-dopaminergic reciprocal inhibitory control in senescence. AB - Previous experiments have indicated that the release of striatal dopamine (DA) is controlled by inhibitory DA autoreceptors which are mediated by inhibitory cholinergic heteroreceptors (HTRs). Activation of the HTRs by muscarinic or nicotine agonists potentiates the K+-evoked release of DA from the striatum. Present experiments were carried out to determine if this relationship is altered as a function of aging. Cross-cut striatal tissue slices obtained from 3 age groups (6, 12-18 and 24 months) Wistar rats were superfused with a modified Krebs Ringer basal release medium containing 2.5 mM KCl. After a 30-min equilibration period, a 5-min baseline fraction was collected from each chamber. The medium was then switched to one containing 30 mM KCl, and depending upon the experiment, 1 of 4 concentrations of a particular muscarinic (oxotremorine, pilocarpine, carbachol or bethanecol) or nicotinic (nicotine) agonist. In some experiments DA autoreceptor function was assessed directly with haloperidol. Six 5-min fractions were taken during depolarization. DA release was assessed using high performance liquid chromatography coupled to electrochemical detection. Results indicated that the efficacy of the muscarinic agonists was reduced in an age-dependent manner with the oldest age groups showing the smallest enhancement. The age at which the decline was seen was dependent on the muscarinic agonist that was applied. Deficits were seen as early as 12 months when full agonists (e.g. carbachol) were applied, but did not appear until 18 months when partial agonists (e.g. oxotremorine) were applied. These age-related alterations were not seen when haloperidol or nicotine were used to enhance the K+-evoked release of DA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900663 TI - Cryopreservation of human fetal adrenal medullary cells. AB - Cryopreservation of human fetal adrenomedullary cells was performed, after dissociation of the gland and purification of chromaffin aggregates, using 10% dymethyl sulfoxide as cryoprotectant. More than 90% of thawed cultured clusters appear morphologically intact, showing extensive neurite outgrowth and absence of appreciable cellular loss. Immunoreactivity for tyrosine hydroxylase and response to nerve growth factor were demonstrated. These findings indicate that human medullary cells maintain their distinctive functional characteristics after cryopreservation. PMID- 2900664 TI - Diurnal alterations in retinal tyrosine level and dopamine turnover in diabetic rats. AB - Retinal tyrosine level is correlated not only to its serum concentration, but also to the serum tyrosine ratio (the ratio of serum tyrosine to the sum of 5 neutral amino acids, leucine, isoleucine, valine, tryptophan and phenylalanine which compete with it for tissue uptake). In control animals, serum tyrosine ratio, retinal tyrosine, dopamine (DA) and its metabolites, and DOPA synthesis exhibit roughly parallel daily rhythms with night-time lows and peak levels occurring in the early portion of the daily light phase (L + 4 HR). In rats made diabetic by streptozotocin injection serum leucine, isoleucine and valine are elevated, lowering the serum tyrosine ratio and retinal tyrosine level by about 50% throughout the daily cycle. Parameters of DA turnover are still highest in the light phase but normal peak levels are delayed by 4 h until the latter half of the light phase (L + 8 HR). In diabetic rats, the normal increase in retinal DA synthesis and release upon exposure to light may be compromised by the decreased availability of its precursor, tyrosine. PMID- 2900665 TI - Differential effects of N-methyl-D-aspartic acid and L-homocysteic acid on cerebellar Purkinje neurons. AB - The effects of N-methyl-D-aspartic acid (NMDA) and L-homocysteic acid (LH) were measured on cerebellar Purkinje neurons. In urethane-anesthetized rats, iontophoretic application of NMDA elicited 3 different effects on the spontaneous activity of Purkinje cells: excitation, inhibition and biphasic responses consisting of excitation followed by inhibition. On the other hand, LH elicited excitation, only, regardless of the actions of NMDA on the same neurons. We also examined the effects of various excitatory amino acid antagonists on NMDA- and LH mediated responses. Excitatory effects of NMDA were antagonized effectively by D.L-2-amino-5-phosphonovalerate (APV), ketamine, gamma-D-glutamylglycine (DGG), D,L-2-amino-7-phosphonoheptanoate (APH), and were not influenced significantly by L-glutamate diethylester (GDEE). Inhibitory responses of NMDA were antagonized by APV, APH and ketamine. LH-mediated excitations were influenced significantly by DGG and ketamine whereas GDEE, APV and APH failed significantly to attenuate the effects of LH. Based on the differential actions of LH and NMDA and the selectivity of NMDA antagonists for NMDA rather than LH-mediated excitations, it appears that the major actions of LH may not be mediated through NMDA receptor sites, at least in the cerebellum. PMID- 2900666 TI - Inactivation of mammalian brain glutamine synthetase by oxygen radicals. AB - Oxygen free radicals have been implicated in ischemic-reperfusion injury to the central nervous system. Ischemic injury to tissue is exacerbated in the presence of the excitatory neurotransmitter, glutamate. Glutamine synthetase is responsible for the conversion of glutamate to its non-toxic metabolite, glutamine, in the CNS. The present paper presents evidence for the inactivation of brain glutamine synthetase by oxygen radicals in vitro and in vivo, and suggests that such a mechanism may underlie the exacerbation of tissue injury in the reperfusion which follows an ischemic insult. PMID- 2900667 TI - Bethanechol-induced increase in hypothalamic estrogen receptor binding in female rats is related to capacity for estrogen-dependent reproductive behavior. AB - Neuroactive agents associated with different neurotransmitter systems can modulate the number of hypothalamic estrogen binding sites. It has been demonstrated previously that the muscarinic cholinergic agonist, bethanechol, administered 30 min prior to in vitro estrogen receptor assays increases the concentration of hypothalamic estrogen binding sites by 30-35% in female rats. Bethanechol was without effect on male hypothalamic preparations. In order to investigate further this sex difference and in an attempt to determine a relationship between the modulation of estrogen binding sites and a sexually differentiated function, bethanechol was given to female rats rendered either anovulatory and capable of displaying lordosis or anovulatory and behaviorally insensitive to estrogen. The results showed that bethanechol significantly increased the number of estrogen binding sites in females capable of displaying lordosis but not in females which did not show this estrogen-dependent behavior. It is possible that the capacity for drug-induced modulation of estrogen binding sites could be related functionally to the ability to display lordosis behavior. PMID- 2900668 TI - Facilitation of hippocampal long-term potentiation in slices perfused with high concentrations of calcium. AB - The effect of increased extracellular calcium on long-term potentiation (LTP) of synaptic transmission has been examined in the CA1 region of guinea pig hippocampal slice preparation using extracellular recordings from the dendritic layer. The application of high calcium (4 mM) led to an increase in the initial slope of the field potential that reversed following return to control (2 mM calcium) solution. The magnitude of the field potential change was unaffected by prior induction of LTP, and inputs tetanized after return to control solution showed the same amount of LTP as those tetanized before the high calcium application. These results suggest that the calcium application by itself did not induce LTP. Inputs tetanized in the high calcium solution showed a greater amount of potentiation than in control solution, any given train producing about twice as much potentiation. However, using long trains (40 impulses) at high strength (2 x test strength) gave similar LTP values in the two solutions. The facilitatory effect of high calcium on LTP was completely blocked by raising extracellular magnesium from 2 to 4 mM. As in control solution. LTP evoked in the high calcium solution was blocked by 2-amino-5-phosphono-valerate. The results support the view that calcium influx through postsynaptic N-methyl-D-aspartate receptor channels is directly involved in the induction of LTP. PMID- 2900669 TI - Maturational changes in retinal excitatory amino acid receptors. AB - The appearance, kinetics and pharmacological properties of receptors for n-methyl D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainate (KA), L-glutamate (Glu) and L-aspartate (Asp) was investigated using 3H-ligand binding during the development of chick embryo retina. Receptors for AMPA are maximally concentrated at embryonic day 7 (ED 7) and decline 50% in subsequent days; L-Glu receptors are low until ED 11, and the same is true for Asp and NMDA receptors which increase at ED 14 and 18 respectively. All receptors studied underwent an increase in pharmacological specificity, whereas only AMPA receptors showed an important change in affinity during ontogeny. Results demonstrate that receptors for excitatory amino acids in the retina suffer maturational changes and suggest that while NMDA and aspartate could interact with the same receptor, AMPA and glutamate seem to bind to different sites. PMID- 2900670 TI - Regeneration of adult rat retinal ganglion cell processes in monolayer culture: comparisons between cultures of adult and neonatal neurons. AB - The aim of the present study was to develop a model culture system for the study of factors controlling regeneration of axons from injured adult mammalian central nervous system. We show, for the first that retinal ganglion cells (RGC) dissociated from adult rat retina, regrow processes in vitro over long distances under over appropriate conditions in monolayer culture. Most importantly, adult RGC depend completely upon the presence of a preformed layer of neonatal cortical astrocytes, whereas RGC from neonatal retinae are supported by indigenous retinal glia which spread and proliferate to form a monolayer of cells upon which RGC regrow processes. Adult retinal glia fail to spread on the culture surface and proliferate in the same way and we suggest that this is a major factor in limiting the survival of adult RGC on an acellular substrate such as polylysine. Laminin does not substitute for the presence of a glial monolayer. These findings indicate that at least one type of adult CNS neuron is capable of regenerating its processes in vitro in an environment which includes a cellular component of CNS tissue. PMID- 2900671 TI - Effects of stimulation of the hypothalamic paraventricular nucleus on blood pressure and renal sympathetic nerve activity. AB - Effects of electrical and chemical stimulation of the paraventricular nucleus (PVN) of the hypothalamus on blood pressure were examined in rats anesthetized with urethane-chloralose. Focal electrical stimulation (10-25 microA, 50 Hz, 0.5 msec) within the PVN consistently decreased blood pressure. Microinjection of L glutamate (0.5 M, 80 n1) into the PVN led to a decrease in blood pressure, while the same amount of saline injection had no effect. The depressor response was not affected by cervical vagotomy. In order to obtain direct evidence for involvement of sympathetic nerve activity in the PVN-induced depressor response, effects of PVN stimulation on renal sympathetic nerve activity were examined. Low intensity electrical stimulation of the PVN inhibited renal sympathetic nerve activity, whereas the high intensity stimulation evoked a transient excitation followed by long lasting inhibition in renal sympathetic nerve activity. Latencies of the inhibitory and the excitatory responses were about 200 msec and 50-100 msec, respectively, judged by peristimulus time histograms. The result suggests that activation of PVN neurons produces a decrease in blood pressure due to inhibition of sympathetic outflows. PMID- 2900672 TI - Neural control of blood glucose homeostasis; effect of microinjection of glucose into hypothalamic nuclei on efferent activity of pancreatic branch of vagus nerve in the rat. AB - Efferent discharges were recorded from the nerve filament dissected from the central cut end of the pancreatic branch of the vagus nerve in the rat. Microinjections of 5% glucose solution (100-200 nl) into the LHA caused an increase in efferent activity, however, those into VMH caused no change in discharge rate. The results of experiments indicate that activation of vagal pancreatic efferents in hyperglycemic situation is originated in LHA and transmitted to the vagal pancreatic motoneurons. The role played by the neural network on blood glucose homeostasis was also discussed. PMID- 2900673 TI - Transmitter and peptide actions on hypothalamic neurons in vitro: implications for lordosis. AB - This article summarizes a series of studies using brain tissue slices of rats to record single-unit activity from the hypothalamic ventromedial nucleus (VMN) and preoptic area (POA), both of which are crucial for the regulation of the estrogen dependent feminine mating behavior, lordosis. In these studies the actions of acetylcholine (ACh), serotonin (5HT), norepinephrine (NE), luteinizing hormone releasing hormone (LHRH), arginine-vasopressin (AVP), and oxytocin (OXY) on neuronal activity were investigated. The results show that these agents could evoke either direct responses or neuromodulatory changes from VMN or POA cells in vitro. Comparison of the net neuronal actions of each of these agents with their effects on lordosis behavior revealed interesting correlations. All the excitatory agents, i.e., ACh, AVP, OXY, and LHRH, have been indicated by intracerebral application studies to be facilitatory on lordosis. The inhibitory agent, 5HT, could inhibit lordosis, when applied to the VMN and its vicinity. Such correlations indicate that these transmitters and peptides can facilitate or inhibit lordosis by increasing or decreasing, respectively, the frequency of action potentials in the types of hypothalamic neurons recorded here. PMID- 2900674 TI - [Ganglionic synapses of Aplysia as a model for the study of the mechanism of action of botulinum neurotoxins]. AB - The action of type A and type B botulinum neurotoxin on neurotransmitter release was studied on identified ganglionic synapses of Aplysia. Using this model, we have shown that botulinum neurotoxins at concentrations used in vertebrate preparations had the same specificity of action and that both heavy and light chains of these toxins are intracellularly required to inhibit neurotransmitter release. PMID- 2900675 TI - [Prenatal diagnosis of phenylketonuria (with a report of 10 cases)]. PMID- 2900676 TI - Effect of microtubule disorganizing or overstabilizing drugs on the proliferation of rat 3T3 cells and their virally induced transformed derivatives. AB - Drugs that disorganize or overstabilize cytoplasmic microtubules (colchicine, vinblastine, griseofulvin, or taxol) can at certain concentrations totally block proliferation of SV40 and polyoma virus transformants with only a minimal effect on the proliferation of the parental rat 3T3 cells. This difference in sensitivity is not due to a more active drug uptake by transformed cells. Examination of cytoplasmic microtubules in actively proliferating normal or transformed cells reveals two categories in each case: cells with microtubules and cells without distinct microtubules. The proportion of cells without distinct microtubules did not differ much between normal and transformed cells. However, transformed cells with a clear microtubule network appear to have fewer microtubules than normal cells. This may contribute to the higher sensitivity of transformed cells. These results render even more rational the use of antimicrotubule drugs in cancer chemotherapy. PMID- 2900677 TI - Characterization of the ATPase activity of the Mr 170,000 to 180,000 membrane glycoprotein (P-glycoprotein) associated with multidrug resistance in K562/ADM cells. AB - The Mr 170,000 to 180,000 membrane glycoprotein associated with multidrug resistance (P-glycoprotein) is involved in drug transport mechanisms across the plasma membrane of multidrug-resistant cells. We have recently reported the purification of P-glycoprotein. The purified P-glycoprotein was found to have an ATPase activity, which might be coupled with the active efflux of anticancer drugs. In the present study, we have further studied the properties of the P glycoprotein ATPase activity by an immobilized enzyme assay procedure using a P glycoprotein-antibody-Protein A-Sepharose complex. GTP was also hydrolyzed by the P-glycoprotein, although less efficiently than ATP. The ATPase activity of P glycoprotein had an optimal pH range around neutrality (pH 6.5-7.4). The detergent concentration of 3-[(3-cholamidopropyl)dimethyl-ammonio]-1-propane sulfonate used for protein solubilization was essential for enzyme recovery. Maximum activity was obtained when 0.1-0.2% 3-[(3-cholamidopropyl)dimethyl ammonio]-propane sulfonate was used, while higher concentrations markedly inhibited the ATPase activity. The ATPase activity was dependent on Mg2+; maximum activity was obtained at 2-10 mM. Manganese and cobalt could substitute for magnesium as ionic cofactors. Divalent cations such as Ca2+, Zn2+, Ni2+, Cd2+, and Cu2+ inhibited the Mg2+-catalyzed ATP hydrolysis. N-Ethylmaleimide and vanadate inhibited the ATPase activity, while sodium azide or ouabain had no effect. Anticancer agents such as vincristine and Adriamycin did not affect the enzyme activity. In contrast, verapamil and trifluoperazine, agents which inhibit active drug efflux and restore drug sensitivity in resistant cells, caused an increase in the P-glycoprotein ATPase activity suggesting that P-glycoprotein might be the target molecule of these agents. PMID- 2900678 TI - Seroepidemiology of human T-cell lymphotropic virus type I infection in Taiwan. AB - The epidemiological characteristics of human T-cell lymphotropic virus type I infection in Taiwan have been explored by an island-wide community-based survey, which was carried out among residents in 19 townships and metropolitan precincts randomly selected through stratified sampling. Serum specimens of 7278 healthy subjects were screened by enzyme-linked immunosorbent assay and confirmed by Western blot method. A total of 103 subjects showed positive or weak reactions by enzyme-linked immunosorbent assay, but only 35 of them were confirmed to be positive by Western blot analysis. The anti-human T-cell lymphotropic virus type I antibody positive rate was 4.81/1000. The seropositive rate increased with age in both males and females, and females had a greater seropositive rate than males for all the age groups. Aborigines and Hakka Taiwanese had higher seropositive rates than Fukien Taiwanese and Mainland Chinese. Those people with lower educational levels were found to be associated with higher anti-human T-cell lymphotropic virus type I seropositive rates. PMID- 2900679 TI - Modulation of hormonal induction of tyrosine aminotransferase and glucocorticoid receptors by aflatoxin B1 and sterigmatocystin in Reuber hepatoma cells. AB - Employing Reuber rat hepatoma cells, H4-II-E, the effects of aflatoxin B1 (AFB1) and sterigmatocystin (STC), which exhibit a similar cytotoxicity but a marked difference in hepatocarcinogenicity, on the hormonal induction of tyrosine aminotransferase (TAT), on glucocorticoid receptors, and on their nuclear acceptor sites were investigated. AFB1 strongly inhibited hydrocortisone inducible TAT activity. The IC50 value was 0.2 micrograms/ml. AFB1 also showed weak inhibitory effects on insulin- and dibutyryl cyclic AMP-inducible TAT activities. In contrast, the IC50 of STC on hydrocortisone-inducible TAT activity was 3.5 micrograms/ml, about 10 times higher than that of AFB1. Dibutyryl cyclic AMP- and insulin-inductions were not depressed by STC. AFB1 inhibited the formation of cytosolic glucocorticoid receptor-hormone complexes (GRCs) but STC did not. Moreover, AFB1, activated in vitro by the microsomal cytochrome P-450 system, interfered more markedly in the formation of cytosolic GRCs than STC did. Sucrose density gradient analysis of GRCs and Scatchard analysis revealed that AFB1 and STC mainly impaired glucocorticoid receptors and GRC-acceptor sites, respectively. The present data suggest a marked difference between AFB1 and STC with regard to the inhibition of hormonal induction of liver specific enzymes. PMID- 2900680 TI - Comparison of constitutive and inducible levels of expression of peroxisomal beta oxidation and catalase genes in liver and extrahepatic tissues of rat. AB - Previous studies from our laboratories have shown that carcinogenic peroxisome proliferators significantly increase the mRNA levels of peroxisomal beta oxidation genes in the rat liver by enhancing the transcriptional activity. Because of a good correlation between the inducibility of peroxisome proliferation and carcinogenicity of this class of xenobiotics, we proposed that sustained induction of peroxisomal beta-oxidation system and the resultant oxidative stress form the basis for carcinogenesis. Since this concept implies that tumors should develop only in tissues which display maximal peroxisome proliferation, we have now assessed the degree to which catalase and the three beta-oxidation genes are expressed in liver and 12 extrahepatic tissues of adult rats fed for 2 weeks a diet containing 0.025% ciprofibrate (w/w), a peroxisome proliferator. In the ciprofibrate-treated rats, the levels of catalase mRNA increased to less than 2-fold in liver, kidney, intestine, and heart, but no change was detected in other tissues. The mRNA levels of the three genes of beta oxidation system in the liver of adult rats treated with ciprofibrate increased greater than 20-fold. In contrast, in the kidney, small intestine, and heart the increases in the mRNA levels of all three beta-oxidation genes were small and varied from 2- to 4-fold following ciprofibrate treatment. Ciprofibrate did not significantly increase the levels of these mRNAs in the other nine tissues. These results correlated well with the levels of peroxisomal beta-oxidation activity, peroxisome volume density, and the immunologically quantified proteins in various tissues. These results provide evidence for the presence of beta-oxidation enzymes in peroxisomes of many tissues of rat and for tissue (cell)-specific differences in the inducibility of mRNAs of these beta-oxidation genes. The marked inducibility of beta-oxidation genes in liver and subsequent development of liver tumors support the hypothesis that tumors develop in tissues that show inducibility of peroxisome proliferation vis a vis beta-oxidation system following exposure to peroxisome proliferators. PMID- 2900681 TI - The neuropharmacology of epileptic falling spells. PMID- 2900682 TI - Therapeutic response to progabide in neuroleptic- and L-dopa-induced dyskinesias. AB - The results of two trials conducted in human dyskinesia with progabide, a specific gamma-aminobutyric acid (GABA) receptor agonist, are reviewed. In one trial, 13 parkinsonian patients with L-DOPA-induced dyskinesia (LDD) and "on-off" fluctuations were included in a double-blind controlled trial progabide versus placebo. No change was observed during this trial in the severity of dyskinesia on progabide treatment but the drug significantly extended the "on" period as compared with placebo. In the second trial, 20 patients with neuroleptic-induced dyskinesia (TD) entered an open dose ranging trial with progabide. Fourteen of the 16 patients who completed the trial had a good-to-excellent therapeutic response. According to these results, progabide does not seem to have the same therapeutic benefit in LDD as TD. These data suggest that the hypothesis of a dopaminergic supersensitivity as a similar pathogenic substrate for both clinical conditions should be reconsidered. If this hypothesis remains the most consistent to explain the occurrence of LDD, the therapeutic effect of progabide in TD is an argument for an implication of the GABAergic system in the appearance of TD. PMID- 2900683 TI - Drug levels and antiparkinsonian drugs in neuroleptic-treated schizophrenic patients. AB - The limitations of antiparkinsonian treatment strategy when using anticholinergic drugs are determined by their side effects induced through excessive inhibition of parasympathetic functions. In the present study we have investigated the peripheral effects of antiparkinsonian agents on blood levels of concomitantly administered neuroleptic drugs. We have compared the anticholinergic and a dopamine mimetic antiparkinsonian agent in their effects on serum neuroleptic activity (SNA) and serum anticholinergic activity (SAA). Sixteen schizophrenic patients on chronic neuroleptic therapy with steady state neuroleptic levels were receiving either amantadine, 200 mg/day, or anticholinergic drugs (trihexyphenidyl, 10 mg/day, or benztropine, 6 mg/day) for the first 2 weeks, after which the amantadine group was crossed over to anticholinergic and the anticholinergic group to amantadine for the following 2 weeks. Blood samples were obtained once a week along with clinical testing. The results indicate that SAA was fivefold higher with benztropine than with trihexyphenidyl and that amantadine had no effect on SAA. Moreover, SNA was not altered either by anticholinergics or amantadine coadministration, indicating that the therapeutic blood neuroleptic levels are not compromised by antiparkinsonian administration. PMID- 2900685 TI - [Study on the geographic epidemiology of epidemic hemorrhagic fever in Fujian]. PMID- 2900686 TI - Percutaneous angioplasty of coronary bypass grafts: an emerging consensus. PMID- 2900684 TI - Cell-specific immuno-probes for the brain of normal and mutant Drosophila melanogaster. I. Wildtype visual system. AB - We have screened antibodies for immunocytochemical staining in the optic lobes of the brain of Drosophila melanogaster. Seven polyclonal antisera and five monoclonal antibodies are described that selectively and reproducibly stain individual cells and/or produce characteristic staining patterns in the neuropile. Such antisera are useful for the cellular characterization of molecular and structural brain defects in visual mutants. In the wildtype visual system we can at present separately stain the following: the entire complement of columnar "T1" neurons; a small set of presumptive serotonergic neurons; some 3000 cells that contain and synthesize gamma-amino butyric acid (GABA); and three groups of cells that bind antibodies to Ca2+-binding proteins. In addition, small groups of hitherto unknown tangential cells that send fine arborizations into specific strata of the medulla, and two patterns of characteristic layers in the visual neuropile have been identified by use of monoclonal antibodies generated following immunization of mice with homogenates of the brain of Drosophila melanogaster. PMID- 2900687 TI - Effects of beta-adrenergic blockade on nitroglycerin-induced augmentation of regional coronary blood flow in patients. AB - Although beta-adrenergic blockade may increase coronary vascular resistance in some patients with severe ischemic heart disease, the effects of beta blockade on the nitroglycerin (NTG)-induced augmentation of coronary blood flow have not been elucidated. Therefore, systemic hemodynamic and anterior left ventricular regional coronary blood-flow (thermodilution) data were measured during administration of NTG into the left coronary artery, before and 10 min after intravenous propranolol (0.1 mg/kg) in 22 patients. Six patients (Group 1) had normal left coronary arteries and nine (Group 2) had severe coronary artery disease with at least greater than 70% narrowing of the left anterior descending artery. In seven additional patients (three without and four with greater than 70% left anterior descending coronary artery disease), measurements were obtained with constant-paced heart rates (Group 3). Before beta blockade, NTG (200 mcg) significantly increased anterior regional great-vein flow [for Group 1, 84 +/- 38% (81 +/- 20 to 140 +/- 60 ml/min); Group 2, 39 +/- 41% (61 +/- 26 to 83 +/- 38 ml/min); and Group 3, 87 +/- 55% (75 +/- 36 to 144 +/- 86 ml/min)]. In Groups 1 and 2, beta-adrenergic blockade reduced heart rate 10% (p less than 0.01) but did not affect mean arterial or pulmonary artery pressures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900688 TI - Cyclin in fission yeast. PMID- 2900689 TI - Crosslinking CD3 with CD2 using sepharose-immobilized antibodies enhances T lymphocyte proliferation. AB - T lymphocyte proliferation can be triggered through interactions with either CD3:Ti, the target of antigen-specific activation, or CD2, the target of an antigen-independent activation pathway. Sepharose-immobilized antibody reactive with CD3 was used to aggregate the T cell receptor complex resulting in T lymphocyte activation. When CD3 was simultaneously crosslinked with CD2 using Sepharose beads coupled to antibodies directed at both determinants, T cell proliferation was markedly enhanced (stimulation index = 8- to 11-fold). A smaller enhancement was induced when CD3 was crosslinked with several other functionally relevant T cell surface molecules. The relative mitogenic potency of the accessory molecules tested was CD2 greater than CD4 greater than CD8 greater than 2H4. Little or no increased proliferation resulted from crosslinking CD3 with class I or class II major histocompatibility antigens. The added proliferation induced by CD3: CD2 crosslinking did not occur in the presence of soluble antibodies directed against CD2. Human thymocytes, the majority of which express both CD3 and CD2, were similarly activated by Sepharose-immobilized antibodies. Our results suggest that specific interactions between T cell surface molecules may play a role in the regulation of lymphocyte activation. PMID- 2900690 TI - Characterization of IL-2-induced murine cells which exhibit ADCC activity. AB - The incubation of murine splenocytes in recombinant interleukin 2 (IL-2) gives rise to both lymphokine-activated killer (LAK) cells capable of lysing fresh tumor cells and cells capable of mediating antibody-dependent cellular cytotoxicity (ADCC) in the presence of anti-H2 allosera. A similarity between these two IL-2-induced cell populations was found. The precursors of the cells mediating these activities were shown to be ASGM1 positive, Thy 1 negative, and radiosensitive. Cells taken from the spleen, thymus, and bone marrow were able to mediate ADCC after culture in IL-2. The effector cell was either Thy 1 positive or negative and was less affected by anti-Thy 1 plus C' treatment than cells which mediated LAK activity. In addition ADCC was exhibited in IL-2-cultured splenocytes from various murine strains and correlated with their LAK activity with one exception. While IL-2-cultured C57BL/6 splenocytes exhibited LAK activity similar to that of C3H LAK cells, no ADCC activity could be demonstrated in C57BL/6 cells. Study of the difference in the ability of these two strains to mediate ADCC revealed that IL-2-induced FcR+ cells in C3H thymocytes, but not in C57BL/6 thymocytes. Based on FACS analysis and on the radiosensitivity of the induction of both FcR+ cells and ADCC, it was suggested that IL-2 was expanding a small FcR+ cell population rather than inducing an increase in FcR density on the cell surface. The relationship between the IL-2-induced ADCC mediator and other IL-2-induced cells, as well as ADCC effector cells, and the possible implications of the results for the in vivo therapy of cancer based on ADCC are discussed. PMID- 2900691 TI - IgE antibody-forming cells in rats infected with Nippostrongylus brasiliensis and immunized with antigens. AB - The distribution of IgE antibody-forming cells was examined in rats infected with Nippostrongylus brasiliensis (Nb) or immunized with Nb antigen or with OA. The frequency of antigen-specific IgE antibody-forming cells was detected by a passive cutaneous anaphylactic (PCA) reaction using cell extract from lymphoid organs. In Nb-infected rats, anti-Nb and anti-4th stage larvae (L4) IgE-forming cells distributed mainly in the mesenteric and the bronchial lymph nodes (LN) near the parasite-harboring sites. After intraperitoneal (ip) immunization with Nb antigen mixed with Al(OH)3 and Bordetella pertussis (Bp) as adjuvants, anti-Nb IgE antibody-forming cells were detected in the mesenteric and the bronchial LN. Anti-Nb or OA IgE antibody-forming cells after subcutaneous (sc) immunization were found in the inguinal and the axillary LN. An effect of Bp on the distribution of IgE antibody-forming cells seems to be ruled out. The distribution of IgG2a antibody-forming cells was similar to that of IgE antibody forming cells, indicating that the distribution of the IgE antibody-forming cells is not preferential. IgE antibody-forming cells were stimulated in the regional LN near the site of antigen administration. IgE antibody-forming cells induced by potentiated IgE antibody production were also examined. Rats were immunized ip or sc with OA and infected with Nb. Anti-OA IgE antibody-forming cells were found in all of the lymphoid organs and especially in the regional LN near the Nb parasite harboring and antigen administration sites. PMID- 2900692 TI - Foot and ankle injuries. PMID- 2900693 TI - Foot and ankle injuries in dancers. AB - Dancing is not dangerous; however, dancers must recognize their limitations and learn to do the best they can with what they have to work with. This article discusses some of the more common acute and chronic foot and ankle problems in dancers for the benefit of the treating physician. PMID- 2900694 TI - The rehabilitation of overuse foot injuries in athletes and dancers. AB - Overuse injuries in athletes and dancers provide a challenge to the diagnostic acumen and rehabilitative and preventive skills of the medical community. The challenge is intensified when the primary lesion is located in the foot, whose levers, arches, and pulleys are responsible for absorbing shock, as well as converting a mobile adapter into a rigid lever for propulsion. A thorough knowledge of these active and passive mechanisms is essential for the appropriate and expeditious management of overuse syndromes. Sports and dance medicine health practitioners must also explore and comprehend the kinesiology of the sports and/or dance activity prevalent among their clientele. Furthermore, in order to determine the etiology and make judicious recommendations, clinicians must familiarize themselves with the density and inclines of popular running and dancing surfaces within their referral area. Rehabilitation of the foot requires a multifaceted approach. Physical therapists dealing with these problems need to develop expertise in manual techniques, along with clinical competency in laser, electrical, and thermal modalities. Reduction of predisposing factors is of utmost importance in the successful management of overuse injuries, and often requires greater skill and attention than does the treatment of the primary lesion. PMID- 2900695 TI - The epidemiology of foot and ankle injuries in sports. AB - A 6 1/2-year review of 16,754 injuries seen in a multispecialty sports medicine clinic found that 25 per cent of the 12,681 injuries in the top 19 sports occurred at the ankle and foot. The percentages of foot and ankle injuries varied substantially from sport to sport, as did the proportion of sprains versus overuse injuries at each location. An appreciation of the patterns and numbers of injuries presenting to a sports medicine facility can be helpful in patient management and can aid the planning of both clinical investigations and educational programs. PMID- 2900696 TI - Polymorphic variations in the ori sequences from the mitochondrial genomes of different wild-type yeast strains. AB - We determined the restriction maps and primary structures of two as yet poorly characterized regions of the mitochondrial genomes of different wild-type strains of Saccharomyces cerevisiae. These regions respectively comprised the ori1 sequence and the newly identified ori8 sequence. Ori1 and ori8, together with their flanking sequences, exhibit a large polymorphism, resulting from specific variations due to insertions or deletions of optional GC clusters at different locations. The mechanisms underlying such sequence rearrangements are discussed. PMID- 2900697 TI - The mitochondrial genome of fertile maize (Zea mays L.) contains two copies of the gene encoding the alpha-subunit of the F1-ATPase. AB - In contrast to the situation in animals and fungi the alpha-subunit of the mitochondrial F1-ATPase is encoded by two identical mitochondrial genes (ATP A) in male fertile maize (Zea mays L.). Cytoplasmic male sterile (T, C and S) maize mitochondrial genomes only contain a single copy of the gene. Sequence analysis reveals that the uninterrupted coding region of both copies of the gene is 1,524 bp long and encodes a polypeptide of 508 amino acids with a molecular weight of 55,117. The predicted amino acid sequence shares over 60% homology with the nuclear encoded alpha-subunit from yeast and bovine ATPase and approx. 50% with the corresponding chloroplast and bacterial polypeptides. PMID- 2900698 TI - Studies on metabolic reduction of befunolol in rabbit liver and kidney. PMID- 2900699 TI - Effect of 3-[2-[4-(o-methoxyphenyl)-1-piperazinyl]ethyl]-2,4(1H,3H)- quinazolinedione monophydrochloride (SGB-1534), an antihypertensive agent, on 3H prazosin and 3H-p-aminoclonidine binding to alpha 1- and alpha 2-adrenoceptors in dog brain and aorta. PMID- 2900701 TI - Qualitative and quantitative effects on epidermal Langerhans (Ia+) and Thy-1+ dendritic cells following topical application of phorbol diesters and mezerein. AB - Repeated twice-weekly applications of promoting doses of 12-O tetradecanoylphorbol-13-acetate (TPA) to the dorsal skin of female adult SENCAR mice led to a reduction in numbers per unit area of epidermal Thy-1+ dendritic cells. Although no parallel effect was observed on Ia+ Langerhans cells, a concurrent reduction of dendritic morphology of both cell types was observed. Topical administration of TPA (2 micrograms) twice weekly for 4 or 8 weeks led to reductions in Thy-1+ cell numbers of 52 and 61%, respectively, whereas a single treatment was without effect. Similar effects were observed in animals initiated with 10 nmol 7,12-dimethylbenz[a]anthracene suggesting that the response was specific to the promotion, rather than the initiation, phase of two-stage tumorigenesis. All initiated animals bore tumors after 16 promoter treatments. In comparison with the potent promoter TPA, the weak overall, but stage-specific promoters 4-O-methylTPA and mezerein showed no effects on number or morphology of either dendritic cell type. These findings are therefore consistent with an important role for quantitative and qualitative alterations in epidermal non keratinocytes of immune function in tumor promotion. PMID- 2900700 TI - Studies on the mechanism of 3-deazaguanine cytotoxicity in L1210-sensitive and resistant cell lines. AB - 3-Deazaguanine (3-DG), a purine analogue, has unusual antitumor activity against experimental mammary tumor models and a number of other solid tumors. Others have shown that mutant CHO cells deficient in hypoxanthine guanine phosphoribosyl transferase (HGPRTase) or adenine phosphoribosyl transferase (APRTase) are resistant to 3-DG. We developed a L1210 cell line resistant to 3-DG, L1210/3-DG, by subculturing the parent L1210/0 cells in the presence of increasing concentrations of 3-DG. The IC50 was 3.5 microM and 620 microM for L1210/0 and L1210/3-DG, respectively. Cytotoxicity studies proved the resistance to be stable. Examination of the baseline-specific activity of HGPRTase and APRTase showed that the former was 118-fold lower in L1210/3-DG than in L1210/0, and the latter demonstrated no difference. A 4-h treatment of the cell lines at IC50 doses showed 48% and 23% reductions in IMP dehydrogenase in L1210/0 and L1210/3 DG, respectively. The rate of de novo purine biosynthesis was studied by using [14C]formic acid. Formate flux increased 2-fold in L1210/3DG in concert with the observed deficiency of HGPRTase in the cell line. 3-DG uptake was studied with [14C]-labelled compound. The total radioactivity was 9-fold higher in L1210/0 than in L1210/3-DG at 2 h. Subsequent chromatographic separation of radioactivity showed the 3-DG and 3-deazaguanosine pools of the drug to be equal in both lines. However, 3-DG nucleotide pools at 1 min and 2 h were 2.5-fold and 16-fold lower, respectively, in L1210/3-DG than in L1210/0. 3-DG incorporation studies with radiolabelled drug demonstrated that 3-deazaguanine is incorporated in the acid insoluble fraction of the cell. These studies conclude that HGPRTase, and not APRTase, is required for the activation of drug. Inhibition of IMP dehydrogenase is partially responsible for antitumor activity of the drug. The incorporation of drug into nucleic acids may be a major mechanism for its antitumor activity. Further studies using a cloned cDNA probe for hypoxanthine guanine phosphoribosyltransferase (HGPRT) demonstrated no change in the DNA arrangements of the L1210/3-DG cell line, and Northern blot analysis showed approximately equal expression of mRNA in both cell lines. PMID- 2900703 TI - Current drug therapy for Tourette's syndrome. PMID- 2900702 TI - Metabolic predisposition of a novel mutant (LEC rats) to hereditary hepatitis and hepatoma: alterations of the drug metabolizing enzymes. AB - Previously we established that 'LEC rats' have displayed spontaneous fulminant hepatitis with severe jaundice, which progressed to liver cancer, and a single autosomal recessive gene is responsible for the cause of the diseases. The activities of drug metabolizing enzymes were assayed in livers from LEC and control (LEA) rats at 4 weeks and 3 months before the onset of liver cancer. At 4 weeks the cytochrome P-450 content of the LEC rat livers was 43% of the control (LEA) value. At 3 months the level was 65% of the control. Epoxide hydrolase, gamma-glutamyltranspeptidase and UDP-glucuronyltransferase activities were 2.6-, 6.9- and 2.4-times higher than those in the LEA rats at 4 weeks, respectively, while glutathione S-transferase activity was not significantly different between the two strains. The enzyme changes in the LEC rats are quite similar to those observed in hyperplastic foci and nodules in chemical carcinogenesis of hepatocytes. PMID- 2900704 TI - Glycemic control and raised serum alanine aminotransferase activity in treated diabetes mellitus. AB - The prevalence of raised serum liver-associated enzyme activity in stabilised, treated diabetic outpatients without concurrent hepatobiliary disease was investigated using a retrospective computer search of biochemical data. The frequency of raised alanine aminotransferase, aspartate aminotransferase, or gamma glutamyl transferase activity found among diabetic, general medical and respiratory outpatients was compared with that found in apparently healthy controls. It was established that a raised activity of any of the three enzymes occurred with a similar frequency in each outpatient group. However, only with alanine aminotransferase did the frequency of elevation (7.1%) in the patients with previously diagnosed hepatobiliary disease exceed that of healthy controls. A raised alanine aminotransferase activity in diabetic outpatients was associated with good glycemic control (hemoglobin A1 less than 8%, p less than 0.02) and treatment with oral hypoglycaemic agents (p less than 0.001). PMID- 2900705 TI - Behaviour of L-gamma-glutamyl-4-nitroanilide and L-gamma-glutamyl-3-carboxy-4 nitroanilide with respect to gamma-glutamyltransferases of different origin. AB - In this paper we compare the measurement of catalytic activity concentrations of gamma-glutamyltransferase with the non-carboxylated and the carboxylated substrate in preparations of different origin. Fresh human sera, commercial test sera and preparations of gamma-glutamyltransferase purified from human liver, porcine kidney and bovine kidney were used as sample materials. When assayed with both substrates preparations of gamma-glutamyltransferase from bovine kidney behaved in a different manner as did the enzyme in preparations from human liver or porcine kidney and the enzyme in fresh human sera. On account of the results obtained with both substrates we classified the commercial test sera for their enrichment using multi-inductive component analysis. The differences observed for the various methods of determination seem to have significance in quality control. PMID- 2900706 TI - gamma-Glutamyl-transpeptidase in diabetics: a case control study. AB - Several investigators have reported high levels of gamma-glutamyl-transpeptidase (GGT) in the diabetic population. Therefore, we undertook a study to see the prevalence of 'isolated' high GGT in a large population of diabetics without chronic liver disease (CLD), as compared to an age- and sex-matched control group of non-diabetic subjects without CLD, and the role of extrahepatic factors in 'isolated' high GGT, as possible etiopathogenetic causes. We selected 351 diabetics with normal hepatologic screening, without echographic abnormalities of the hepatic parenchyma or the biliary tract. Age, duration and therapy of diabetes, body mass index (BMI), alcohol consumption, glycosylated hemoglobin (HbA1), and the presence of hepatitis B virus (HBV) were studied to see if they are related to high GGT. The control group included 260 age- and sex-matched non diabetic subjects. We did not find any significant difference between diabetics and the control group in the prevalence of high GGT (mean: 17.5% vs. 23%; women: 16% vs. 14.5%). Multiple regression analysis showed that alcohol consumption plays the major role in the high GGT of both men and women. PMID- 2900707 TI - The gene for incontinentia pigmenti: failure of linkage studies using DNA probes to confirm cytogenetic localization. AB - Probes for restriction fragment length polymorphisms mapping between Xp21 and Xq22.3 have been used in a linkage study of incontinentia pigmenti (IP). Six independent sporadic cases of disorders resembling IP with X-autosome translocations involving the same X chromosome breakpoint (Xp11) have been reported. These observations suggest that the IP gene may be located in the Xp11 chromosomal region. However, the linkage study with DNA probes has failed to confirm this localisation. PMID- 2900708 TI - Recombinational event between Norrie disease and DXS7 loci. AB - We have identified a family affected with X-linked recessive Norrie disease, in which a recombinational event occurred between the disease locus and the DXS7 locus identified by the probe L1.28. The addition of our family brings the total of published informative families to seven, with a maximum lod score of 7.58 at a recombination frequency of 0.038 +/- 0.036. This finding indicates that the L1.28 probe is useful but may not be completely reliable for prenatal diagnosis and that the gene for Norrie disease is not within the DNA sequence identified by the L1.28 probe. PMID- 2900709 TI - Dynamic heterogeneity: metastatic variants to liver are generated spontaneously in mouse embryonal carcinoma cells. AB - Mouse embryonal carcinoma (EC) cells derived from F9 cells form predominantly liver tumors following the intravenous injection (i.e. experimental metastasis assay) of EC cells into syngeneic 129/J male mice. In this study, EC cells (OTF9) expressing stage-specific embryonic antigen-1 (SSEA-1) are compared with cells (SOTF9) lacking SSEA-1 antigen in the experimental liver metastasis assay. When parallel clones of EC cells were grown to a measured cell number and tested in the experimental metastasis assay, it was observed that the frequency of experimental liver metastases increases with the population size. When the clonal population size is less than the critical number of cells (approximately 2 x 10(5) cells), the frequency of liver tumors is reduced relative to that of the parent EC population. The metastatic ability of clones derived from individual liver metastases did not differ from that of the parental cells. An analysis of the recessive biochemical and immunochemical markers of parental cells and of independent liver metastases suggests that somatic hybridization to host cells by the EC cells is not involved. These results are consistent with predictions from our dynamic heterogeneity model that was formulated by examining the experimental lung metastasis of KHT fibrosarcoma and B16 melanoma cells. Mathematical analysis of the results indicates that the effective rate of generation of the liver metastasizing variant cells is (7 +/- 3) x 10(-6) per cell per generation for both OTF9 and SOTF9 cells. PMID- 2900710 TI - [Somatostatin-immunoreactive neurons in the amygdaloid complex in patients with Alzheimer type dementia and aged controls]. PMID- 2900711 TI - Pharmacotherapy of the hospitalized young adult schizophrenic patient. AB - The authors surveyed pharmacotherapy in a group of hospitalized 18 to 35-year-old young adult patients (N = 286) with a DSM-III diagnosis of schizophrenia. Drug use comparisons were made between patients with a 180 day or less hospitalization (short-stay, N = 226) and those with a 366+ day hospitalization (long-stay, N = 60). Psychotropic drug usage during the initial 180 and most-recent 180 days of treatment of the long-stay group was compared with the total episode of the short stay group. Antiepileptic, antidepressant, lithium and anxiolytic/sedative/hypnotic agents, were used in significantly more of the long stay than short-stay patients. This increase was not observed between the two groups for the initial 180 days of the long-stay group but was observed during the most recent 180 days of treatment. Antipsychotic mean daily doses and patterns of use in the two length of stay groups were similar. Chlorpromazine (CPZ) dosage was significantly increased in long-stay patients compared with short-stay patients (P less than .05). PMID- 2900712 TI - Psychosis, behavioral disturbance, and the use of neuroleptics in dementia. AB - Despite the widespread use of psychotropic agents in patients with dementia, there is little available research on the nature and prevalence of psychiatric disturbance and behavioral syndromes requiring this treatment, and the results of such therapy. The authors suggest strategies to overcome difficulties inherent in attempting to obtain symptom profiles in demented patients. There is weak evidence to support the use of neuroleptics in the treatment of symptoms like suspiciousness, hallucinations, sleeplessness, agitation, emotional liability, and aggressiveness; no individual neuroleptic can be considered superior to any other for this purpose. Few studies have evaluated the effect of neuroleptics on activities of daily life (ADL), and no study has used detailed neurophsychological evaluation to examine their effects on cognitive function in dementia. PMID- 2900713 TI - Significance of mixed features in acute mania. AB - We studied a group of 23 manic patients to ascertain the prognostic significance of mixed affective features. Eight patients (34.8%) presented with a mixed manic state. This mixed state correlated with a longer hospitalization and significantly worse disposition outcome. In the light of previous conceptual models the authors speculate about the meaning of DSM-III defined mixed bipolar disorder. PMID- 2900715 TI - Experimental study on the effects of adrenergic blockade to multiple organ failure. PMID- 2900714 TI - Effect of sulfasalazine and its analogs on fertility in male rats. AB - Several derivatives of sulfasalazine were tested for their antifertility activity in male rats. The compounds were administered to groups of rats daily by oral gavage for 28 days. Fertility of the rats treated with sulfasalazine or compound CH 74A was reduced, while other compounds had no effect. In a subsequent experiment, therefore, only the active compounds were studied further. Fertility of rats treated with sulfasalazine, compound CH 74A, CH 99A or sulfapyridine was reduced during 40 days of treatment. At the end of treatment, body weights were reduced in higher dose groups of sulfasalazine, CH 74A and sulfapyridine compared to control animals. The weights of the testes, prostate or seminal vesicle were not altered by any of the treatments. On the other hand, weight of the epididymides decreased in all higher dose groups except in CH 99A-treated animals. Sperm motility decreased in all the treated rats except in animals treated with low dose of sulfapyridine, whereas epididymal sperm count decreased in all but CH 99A-treated animals. These results suggest that sulfasalazine and its derivatives bring about their antifertility effects by decreasing sperm motility and/or number of spermatozoa. PMID- 2900716 TI - Developmental regulation of prion protein mRNA in brain. AB - During development of the hamster brain, synthesis of the cellular isoform of the scrapie prion protein (PrPC) was found to be regulated. Low levels of PrP poly(A)+ mRNA were detectable one day after birth. PrP poly(A)+ mRNA reached maximal levels between 10 and 20 days post-partum; thereafter, no change in its level could be detected at ages up to 13 months. In contrast, myelin basic protein poly(A)+ mRNA was shown to reach maximal levels by 30 days of age and thereafter steadily declined in adult brain. Using monospecific PrP antisera, immunoprecipitable cell-free translation products were detected at low levels two days after birth and progressively increased up to 10 days of age. How the PrP mRNA participates in brain development and its function in scrapie prion infection are being investigated. PMID- 2900717 TI - Scrapie: a virus-induced amyloidosis of the brain. AB - We have studied the pathogenesis of scrapie in hamsters, in particular the increase of infectivity and the formation of scrapie-associated fibrils in relation to clinical disease. The results of such studies after intraperitoneal or intracerebral infection are consistent with the idea that transmissible spongiform encephalopathies are a type of virus-induced, brain-specific amyloidosis. Therefore, an appropriate name for the class of viruses that cause these diseases might be amyloid-inducing viruses. PMID- 2900718 TI - Scrapie-associated fibrils, PrP protein and the Sinc gene. AB - Scrapie-associated fibrils (SAF) are disease-specific structures found in extracts of the brains of animals affected with scrapie. These structures are pathological aggregates of a normal host protein called PrP. In collaboration with Konrad Beyreuther (Heidelberg), we have characterized the multiple forms of PrP found in SAF fractions from mouse brain affected by the ME7 strain of scrapie. There is no in vivo N-terminal cleavage of the most abundant forms of PrP. However, N-terminal cleavage of some minor forms of PrP does occur in vivo within a domain of repetitive sequences at sites similar to but distinct from those cut by proteinase K in vitro. We suggest that such covalently modified forms of PrP may be the result of enzymic degradation occurring as a consequence rather than as a cause of disease. We also found a novel, as yet unidentified, amino acid derivative of the arginine residue at position 3 in both hamster and mouse PrP 33-35, which may predispose PrP to form SAF. Carlson and colleagues have discovered a linkage between the PrP gene and the murine gene provisionally called Prn-i which, from the work of Carp and coworkers, appears identical to the Sinc gene. The Sinc gene is the major gene determining the incubation period of all strains of scrapie in mice. We have evidence for a linkage of the PrP gene and Sinc using inbred mice of known Sinc genotype, including VM(Sincp7) and VM(Sincs7) congenic mice. PrP may even be the protein product of the Sinc gene. PMID- 2900719 TI - Properties of scrapie prion proteins in liposomes and amyloid rods. AB - The scrapie prion protein (PrP 27-30) has been demonstrated to be required for infectivity. Aggregates of PrP 27-30 form insoluble amyloid rods which resist dissociation by non-denaturing detergents. Mixtures of the detergent cholate and phospholipids were found to solubilize PrP 27-30 with full retention of scrapie prion infectivity. No evidence for a prion-associated nucleic acid could be found when the phospholipid vesicles with PrP 27-30 were digested with nucleases and Zn2+. Under digestion conditions which allowed hydrolysis of exogenous nucleic acids, no diminution of prion infectivity was observed. Tobacco mosaic virions added to the liposomes at a concentration 100 times lower than the scrapie prion titre could be seen by electron microscopy. These studies indicate that there is no subpopulation of filamentous scrapie viruses hidden amongst the prion rods - indeed, they would have been observed among the liposomes. The partitioning of PrP 27-30 and scrapie infectivity into phospholipid vesicles argues for a central role of PrP 27-30 in scrapie pathogenesis and establishes that the prion amyloid rods are not essential for infectivity. PMID- 2900721 TI - Genetic control of prion incubation period in mice. AB - The prion gene complex (Prn) is located on mouse chromosome 2 between the beta-2 microglobulin (B2m) and agouti (A) genes. Within this complex are the prion protein gene (Prn-p), which encodes the only identified macromolecule (PrP) that purifies with infectious scrapie agent, and a scrapie incubation time gene (Prn i). Using a variety of restriction endonucleases, six allelic forms of the Prn-p gene have been distinguished by their patterns of restriction fragment length polymorphisms. We had previously shown that the exceptionally long scrapie incubation period of I/LnJ mice inoculated with the Chandler isolate (over 200 days) was due to the effects of a scrapie incubation time gene tightly linked to Prn-p. So far, this long scrapie incubation time allele has been found only in those inbred mouse strains (I/LnJ, P/J and IM) that have the b allele of Prn-p. It is not known whether the incubation time gene and prion protein gene are two distinct loci or are one and the same. Putative recombinants between the incubation time phenotype and Prn-p genotype have been observed, but this could be due to effects of other genes segregating in the population. Regardless of whether or not the incubation time and PrP genes are identical, if any differences were found in the amino acid sequences of PrP encoded by the different Prn-p alleles there would be important implications for interpretation of results on 'strains' of scrapie agent. It would not be necessary to invoke nucleic acid as the informational macromolecule of the scrapie agent because differences in prion 'strains' recovered from mice with different Prn-p genotypes need not be the result of host selection but could be due to differences in host encoded PrP. PMID- 2900722 TI - Enzymatic hydrolysis of retinamides. AB - Enzymatic activity present in liver microsomes from rats slowly hydrolyzed N-(4 hydroxyphenyl)retinamide (4HPR). A product of the reaction was all-trans-retinoic acid. The reaction, which had a pH optimum greater than 8.6, was stimulated by divalent cations, particularly Mn2+. Enzyme activity was highest in liver microsomes but was also present in kidney microsomes, liver cytoplasm, and spleen cytoplasm. Of 10 possible substrates tested, the 13-cis- and all-trans-forms of N ethylretinamide were most active. The all-trans-form of 4HPR was much more active than the 13-cis-form. Neither 13-cis- nor all-trans-retinoyl leucine was a substrate. Because no detectable [14C]all-trans-retinoic acid could be found in the livers of rats after doses of [14C]4HPR, we conclude that this enzyme is not extensively active in intact animals. PMID- 2900720 TI - Novel mechanisms of degeneration of the central nervous system--prion structure and biology. AB - Prion is a term for the novel infectious agents which cause scrapie and Creutzfeldt-Jakob disease; these infectious pathogens are composed largely, if not entirely, of prion protein (PrP) molecules. No prion-specific polynucleotide has been identified. Considerable evidence indicates that PrP 27-30 is required for and inseparable from scrapie infectivity. PrP 27-30 is derived from a larger protein, denoted PrPSc. A cellular isoform, designated PrPC, and PrPSc are both encoded by a single copy chromosomal gene and both proteins appear to be translated from the same 2.1 kb mRNA. Monoclonal antibodies to PrP 27-30 as well as antisera to PrP synthetic peptides, react with both PrPC and PrPSc, establishing the relatedness of these proteins. PrPC is completely digested by proteinase K; PrPSc is converted to PrP 27-30 under the same conditions. Detergent extraction of microsomal membranes isolated from scrapie-infected hamster brains solubilizes PrPC but induces PrPSc to polymerize into amyloid rods. This procedure allows separation of the two prion protein isoforms and the demonstration that PrPSc accumulates during scrapie infection while the level of PrPC does not change. The prion amyloid rods generated by detergent extraction are identical morphologically, except for length, to extracellular collections of prion amyloid filaments which form plaques in scrapie- and CJD-infected brains. The prion amyloid plaques stain with antibodies to PrP 27-30 and PrP peptides. Prion rods composed of PrP 27-30 dissociate into phospholipid vesicles with full retention of scrapie infectivity. The murine PrP gene (Prn-p) is linked to the Prn-i gene, which controls the length of the scrapie incubation period. Prolonged incubation times are a cardinal feature of scrapie and CJD. While the central role of PrPSc in scrapie pathogenesis is well established, the chemical and conformational differences between PrPC and PrPSc are unknown but presumably arise from post-translational events. PMID- 2900724 TI - Suppression of acetaminophen conjugation and of conjugate elimination in the rat by metyrapone, a classical P-450 inhibitor. AB - This study examined the effects of metyrapone on the overall elimination of acetaminophen and on the individual processes principally responsible for elimination, the formation of acetaminophen sulfate and glucuronide. Because acetaminophen pharmacokinetics are nonlinear above a threshold dose, experiments were designed to investigate acetaminophen elimination in the linear (30 mg/kg) and nonlinear (150 mg/kg) ranges to assess possible effects of metyrapone on conjugating enzymes and on cofactor availability. Prior treatment with 400 mg/kg metyrapone tartrate decreased total clearance of acetaminophen over 30% in the linear range (25.4 +/- 2.0 vs. 36.2 +/- 3.7 ml/min/kg in controls; p less than 0.01) and over 40% in the nonlinear range of disposition (4.42 +/- 1.07 vs 7.76 +/- 1.37 ml/min/kg in controls, p less than 0.01). Partial clearance to acetaminophen glucuronide was decreased by metyrapone in each dose range. Partial clearance to acetaminophen sulfate also declined in each dose range but statistically so only after 150 mg/kg. Metyrapone decreased the renal clearance of acetaminophen sulfate and glucuronide when these conjugates were formed in vivo after acetaminophen administration. However, metyrapone failed to impair the renal clearance of acetaminophen glucuronide when preformed metabolites were administered directly. The utility of metyrapone as a specific inhibitor of oxidative drug metabolism appears to be limited for drugs such as acetaminophen by concomitant inhibition of competing conjugation pathways, which account for the majority of drug elimination. PMID- 2900723 TI - Genetic control of acetyl coenzyme A-dependent arylamine N-acetyltransferase, hydrazine N-acetyltransferase, and N-hydroxy-arylamine O-acetyltransferase enzymes in C57BL/6J, A/J, AC57F1, and the rapid and slow acetylator A.B6 and B6.A congenic inbred mouse. AB - Acetyl coenzyme A-dependent N-acetyltransferase and O-acetyltransferase activities were examined in liver cytosols derived from homozygous rapid acetylator C57BL/6J and A.B6 congenic inbred mouse strains, from homozygous slow acetylator A/J and B6.A congenic inbred mouse strains, and from the (C57BL/6J x A/J)F1 heterozygous acetylator hybrid mouse strain. Acetylator genotype-dependent N-acetyltransferase activity was exhibited for the N-acetylation of p aminobenzoic acid, 2-aminofluorene, and 4-aminobiphenyl. In contrast, levels of isoniazid N-acetyltransferase and N-hydroxy-3,2'-dimethyl-4-aminobiphenyl O acetyltransferase activities in mouse liver cytosol appeared to be independent of the arylamine Nat acetylator gene. Although cytosolic N-acetyltransferase activities differed about 2-fold between the parental C57BL/6J and A/J strains for p-aminobenzoic acid, 2-aminofluorene, and 4-aminobiphenyl, the same N acetyltransferase activities differed about 6-7-fold between the homozygous rapid acetylator A.B6 and the homozygous slow acetylator B6.A congenic inbred strains. Partial purification of acetyl coenzyme A-dependent arylamine N-acetyltransferase activity in the five inbred mouse strains showed one major paraoxon-resistant enzyme in liver cytosol in each of the rapid and slow acetylator mouse strains examined. Levels of partially purified 2-aminofluorene and 4-aminobiphenyl N acetyltransferase activity were about 7-fold higher in the A.B6 than the B6.A congenic inbred strain. Partial purification of acetyl coenzyme A-dependent isoniazid N-acetyltransferase activity showed catalysis by a paraoxon-resistant enzyme(s) distinct from the major arylamine N-acetyltransferase enzyme(s). These results suggest that isoniazid N-acetyltransferase(s) in mouse liver cytosol is a product of a separate gene that segregates independently of the arylamine Nat gene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900725 TI - Inhibition of the metabolism of urethane by ethanol. AB - Ethanol has been shown to inhibit the localization of [ethyl-1-14C] urethane in the male mouse, but the effect of ethanol on the metabolism of urethane has not been clarified. Consequently, the concentration of unchanged urethane was determined in the blood of male mice up to 11 hr after oral administration of urethane with or without ethanol. A high and constant blood level of urethane persisted for 8 hr after the administration of an ethanolic solution of [ethyl-1 14C] urethane (125 mumol/kg, 10 muCi/20 g of mouse, 5 g of ethanol per kg, po); the blood level of ethanol was at or above 150 mg/dl during these 8 hr. In contrast, rapid clearance of radioactivity was observed in mice treated with [ethyl-1-14C]urethane dissolved in water. Coadministration of ethanol with urethane decreased the rate of 14CO2 expiration; furthermore, covalent binding with liver protein was delayed about 8 hr and was less than that in the group treated with urethane in water. The metabolism of urethane and production of 14CO2 from [carbonyl-14C]urethane by mouse liver homogenate in vitro were inhibited by the presence of ethanol (greater than 10 mM); these concentrations of ethanol in vitro are about the same as those that are inhibitory in vivo, but the extent of inhibition suggests that the liver is not the only site of metabolism of urethane. These results indicate that ethanol can inhibit the initial metabolism of urethane, prevent the formation of active metabolites, and allow urethane to persist in blood. PMID- 2900726 TI - Benzazepine metabolism revisited. Evidence for the formation of novel amine conjugates. AB - Three novel metabolites of the benzazepine SK&F 86466 (6-chloro-2,3,4,5 tetrahydro-3-methyl-1H-3-benzazepine) have been isolated from dog urine and characterized by tandem mass spectrometry, using fast atom bombardment and thermospray ionization, and 1H and 13C NMR spectroscopy. The parent drug undergoes oxidation to yield an N-oxide or N-demethylation to yield the primary metabolite SK&F 101055 (6-chloro-2,3,4,5-tetrahydro-1H-3-benzazepine). This desmethyl metabolite then undergoes N-sulfoconjugation to yield 6-chloro-2,3,4,5 tetrahydro-1H-3-benzazepine-3-N-sulfonate. Two glucuronide conjugates derived from the desmethyl metabolite were also isolated and characterized. One glucuronide is formed from an intermediate carbamic acid, formally derived from the addition of CO2 to the desmethyl benzazepine. A second glucuronide is derived from an intermediate hydroxylamine metabolite. Methodology for characterizing the carbamyl glucuronide was developed, using an ethanolysis reaction to give a stable ethyl carbamate derivative that can then be characterized by GC-MS. This methodology should prove useful in establishing whether such carbamylation reactions occur with other amines. PMID- 2900727 TI - Pharmacokinetics of a series of 6-chloro-2,3,4,5-tetrahydro-3-substituted-1H- 3 benzazepines in rats. Determination of quantitative structure-pharmacokinetic relationships. AB - To aid in the effort to discover novel agents for the treatment of cardiovascular disease, the relationships between pharmacokinetic parameters in the rat and lipophilicity and basicity were studied for a series of 6-chloro-2,3,4,5 tetrahydro-3-substituted-1H-3-benzazepines. Eight compounds, ranging in lipophilicity from log P = 1.64 to 3.50 and basicity from pKa = 6.75 to 9.36, were studied. The compounds were administered iv to rats, and the pharmacokinetic parameters were calculated from the plasma concentration-time curves. Plasma protein binding was determined in vitro using equilibrium dialysis to allow calculation of steady state volume of distribution of unbound drug, Vss,u; and tissue binding. Stepwise regression analysis with each pharmacokinetic parameter as the dependent variable and log P and pKa as the independent variables was performed. In no case was there a significant relationship between a pharmacokinetic parameter and both of the independent variables. Statistically significant linear relationships were found between pKa and Vss and t 1/2z. Lipophilicity was found to correlate with the free fraction in plasma and the free fraction in tissues. The clearance parameters did not correlate with either of the physicochemical parameters. The pharmacokinetics of the one secondary amine in the series were clearly different from those of any of the tertiary amines. The clearance of the secondary amine was lower and the volume of distribution higher than any of the tertiary amines. These results demonstrate that alteration of the lipophilicity of 3-substituted benzazepines does not alter their pharmacokinetics in a predictable fashion but that the pharmacokinetics of secondary amines may be substantially different than tertiary amines. PMID- 2900728 TI - Pharmacokinetic procedures for the estimation of organ clearances for the formation of short-lived metabolites. Acetaminophen-induced glutathione depletion in hamster liver. AB - Several approaches have been developed to estimate in vivo the intrinsic clearances of enzymes that catalyze the formation of chemically reactive metabolites that do not escape the organs in which they are formed. Two basic models are considered. Model 1 is a general model in which the chemically reactive metabolite is inactivated by a combination of a pseudo-first order reaction, such as a reaction with large pools of protein, and a second order reaction with a depletable endogenous substance, such as glutathione or an enzyme. Model 2 is a special case, in which at low doses of the parent compound the reactive metabolite preferentially reacts with a depletable endogenous substance, such as glutathione. In developing both models we have assumed that the rate of formation of reactive metabolite follows first order kinetics and that the concentration of reactive metabolite in liver reaches a steady state almost instantaneously. In developing Model 2 we also have assumed that the depletion of hepatic reduced glutathione is due solely to the formation of glutathione conjugates. The uses of the approaches based on Model 2 were illustrated by studying the effects of a marginally toxic dose of acetaminophen on the depletion and subsequent repletion of hepatic glutathione in hamsters. From the calculated rate of synthesis of glutathione in liver, the fraction of the dose of acetaminophen converted to the glutathione conjugate in liver, and the clearance for the formation of glutathione conjugate in vivo was estimated and was found to be similar to that obtained with hepatic 9,000 g supernatant preparations. Other uses of the models are described. PMID- 2900729 TI - Hydroxy metabolites of phencyclidine. Identification and quantitation of two novel metabolites. AB - A new sensitive and specific GC-MS assay was developed to quantify monohydroxy metabolites of phencyclidine (PCP) from biological samples. The method is based on the two-step extraction of PCP and related basic metabolites in an organic solvent followed by a capillary column GC separation and mass selective detection of the extract derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide. The detection limit of the method is about 5 pmol with a linear standard curve to 3 nmol/injection. The assay was used for the quantification of monohydroxy metabolites in the urine of PCP-dosed mice and rats. A new compound (specifically selected for this study), 1-phenyl-1-(1-[3-hydroxymethyl]piperidinyl)cyclohexane, was used as the internal standard. The internal standard was selected to closely mimic the chemical characteristics of potential alicyclic hydroxy metabolites of PCP. The in vitro biotransformation of PCP by mouse and rat liver microsomes also was studied. The presence of a recently identified metabolite, 3-phenyl-3-(1 piperidinyl)-trans-cyclohexanol was confirmed. A new metabolite, 1-phenyl-1-(1 piperidinyl-3-ol)cyclohexane, was identified and quantified in the urine and liver microsomal preparations. PMID- 2900730 TI - Differential renal handling of angiotensin-converting enzyme inhibitors enalaprilat and lisinopril in rats. AB - Enalaprilat, the active metabolite of enalapril, and its lysine analogue lisinopril are potent nonsulfhydryl angiotensin-converting enzyme inhibitors. Earlier studies from our laboratories demonstrated that neither drug is significantly metabolized, and both are almost exclusively eliminated by renal excretion. This report compares the renal excretory mechanisms for these structurally related compounds in the rat. After an iv, 1-mg/kg dose, ratios of renal clearance (CLR) of unbound drug to glomerular filtration rate (GFR) for enalaprilat and lisinopril were 2.72 +/- 0.70 and 1.01 +/- 0.18, respectively, suggesting that enalaprilat, but not lisinopril, was actively secreted by the kidneys. Treatment with probenecid and p-aminohippuric acid, potent competitive inhibitors for the renal anionic transport system, caused a profound decrease in the renal clearance of enalaprilat to the level of GFR. The CLR/fu.GFR, where fu is the unbound fraction, became 1.10 +/- 0.09 and 1.25 +/- 0.25, respectively. These results and the fact that quinine, a potent inhibitor for the cationic transport system, had little effect on the renal clearance of enalaprilat indicated that enalaprilat is secreted by the organic anion transport system. On the other hand, probenecid, p-aminohippuric acid, and quinine had no effect on the renal clearance of lisinopril, suggesting that lisinopril is eliminated exclusively by glomerular filtration. PMID- 2900731 TI - Metabolism-dependent covalent binding of (S)-[5-3H]nicotine to liver and lung microsomal macromolecules. AB - Incubation of (S)-[5-3H]nicotine with rabbit liver microsomes in the presence of dioxygen and NADPH results in the formation of metabolites that bind covalently to microsomal macromolecules (250-550 pmol/mg of protein/hr). The partition ratio [(S)-nicotine metabolized/(S)-nicotine equivalents covalently bound] ranged between 250:1 and 500:1. The addition of SKF 525-A, cytochrome c, or n-octylamine inhibited both (S)-nicotine metabolism and covalent binding whereas phenobarbital pretreatment increased the rates of metabolism and covalent binding. Sodium cyanide, which forms stable adducts with the cytochrome P-450-generated iminium ion metabolites of (S)-nicotine and a variety of other tertiary amines, inhibited covalent binding but also decreased the rate of (S)-nicotine metabolism. The metabolism-dependent covalent binding of (S)-nicotine and its conversion to the delta 1',5'-iminium species were observed also in microsomal incubations prepared from rabbit lung and human liver tissues. PMID- 2900732 TI - Excretion and biotransformation of cisapride in dogs and humans after oral administration. AB - The excretion and biotransformation of cisapride, a novel gastrokinetic drug, were studied after a single po dose of [14C]cisapride in dogs and humans. The excretion of radioactivity amounted to 97% within 4 days after a 1 mg/kg dose in dogs (72% in feces and 25% in urine). After a 10-mg dose in humans, 44% was excreted in the 0-24-hr urine and 37% in the 0-35-hr feces; excretion was complete within 4 days. Excretion of the parent drug was greater in dogs (0.4 1.3% of the dose in urine, 23% in feces) than in humans (0.2% in urine, 4-6% in feces). This was due, at least in part, to a larger proportion of amine glucuronidation and sulfation in dogs. N-Deal-kylation at the piperidine nitrogen resulting in the main urinary metabolite, norcisapride, and aromatic hydroxylation of the 4-fluorophenyl ring were major metabolic pathways in both species. Norcisapride excretion accounted for 14% of the dose in dogs and 41-45% in humans. Minor metabolic pathways were O-dealkylation at the 4-fluorophenoxy group and piperidine oxidation. Peak plasma levels and AUC values of norcisapride in humans were 8-9 times lower than those of cisapride. Apart from more amine conjugation in dogs, the biotransformation of cisapride was similar in dogs and humans. PMID- 2900733 TI - Excretion and biotransformation of cisapride in rats after oral administration. AB - The excretion and biotransformation of cisapride, a novel gastrokinetic drug, were studied after single (10, 40, and 160 mg/kg) and repeated (10 mg/kg/day) po administration to rats, using three different radiolabels. In fasted rats, cisapride was absorbed almost completely, except for the 160 mg/kg dose. Cisapride was metabolized extensively to at least 30 metabolites. The excretion of the metabolites amounted to more than 80% of the dose at 24 hr and was almost complete at 96 hr after dosing. In bile duct-cannulated rats, 60% was excreted in the bile within 24 hr, 45% of which underwent enterohepatic circulation. The main urinary metabolites, 4-fluorophenyl sulfate and norcisapride, primarily resulted from the N-dealkylation at the piperidine. Another major metabolic pathway was aromatic hydroxylation, occurring on either the 4-fluorophenoxy or the benzamide rings. The resulting phenolic metabolites were eliminated as conjugates in the bile; a large portion of them were subjected to a rapid enterohepatic circulation before their final excretion in the feces. Minor metabolic pathways included piperidine oxidation, O-dealkylation, O-demethylation of the methoxy substituent at the benzamide, and amine glucuronidation. Only minor quantitative dose- and sex-dependent differences could be observed for the mass balance of the metabolites. Upon repeated po dosing, steady state excretion rates were already attained after two to three doses, and excretion and metabolite patterns were very similar to those after single dose administration. PMID- 2900734 TI - Stereoselectivity and regioselectivity of purified human glutathione transferases pi, alpha-epsilon, and mu with alkene and polycyclic arene oxide substrates. AB - The stereoselectivities of three biochemically distinct human glutathione transferases, the acidic isoenzyme (pi) purified from placenta and the basic (alpha-epsilon) and the near-neutral (mu) isoenzymes purified from liver, were determined with (+/-)-benzo(a)pyrene-4,5-oxide, pyrene-4,5-oxide, and (+/-) styrene-7,8-oxide as substrates. Transferase mu was highly selective (greater than 95%) for reaction of glutathione with R-configured oxirane carbon atoms of (+/-)-benzo(a)pyrene-4,5-oxide and pyrene-4,5-oxide, whereas transferase pi was highly stereoselective (greater than 95%) for S-configured epoxide carbon atoms of (+/-)-benzo(a)pyrene-4,5-oxide and pyrene-4,5-oxide. The basic transferases (alpha-epsilon) showed relatively low stereoselectivity with these polycyclic arene oxide substrates; glutathione reaction at R-configured oxirane carbons was preferred, but only by about 2-fold. With (+/-)-benzo(a)pyrene-4,5-oxide as substrate, transferases mu and alpha-epsilon were enantioselective for (4R,5S) benzo(a)pyrene-4,5-oxide (about 6-fold), whereas transferase pi showed little enantioselectivity. With (+/-)-styrene-7,8-oxide as substrate, transferases mu and pi were selective for (7S)-styrene-7,8-oxide, but this enantioselectivity was not great (1.3- to 1.8-fold); enantioselectivity could not be accurately determined with alpha-epsilon due to the low enzymatic turnover. Transferase pi selectively catalyzed the reaction of glutathione with the benzylic oxirane carbon (C-7) of (+/-)-styrene-7,8-oxide whereas alpha-epsilon preferentially catalyzed reaction with the terminal epoxide carbon (C-8) atom.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900735 TI - Species differences in the stereoselective hydrolysis of esmolol by blood esterases. AB - The stereoselective hydrolysis of esmolol was examined in blood from several species including humans. Blood esmolol esterase activity was in the order of guinea pigs greater than rats greater than rabbits greater than dogs greater than rhesus monkeys greater than humans. Dog and rat blood esterases hydrolyzed the ( )-enantiomer of esmolol faster than the (+)-enantiomer whereas rhesus monkey, rabbit, and guinea pig blood esterases hydrolyzed the (+)-enantiomer faster. Human blood esterases did not demonstrate stereoselectivity. Dog liver esterases also showed stereoselectivity towards the (-)-enantiomer but dog skeletal muscle esterases did not. Studies in mongrel dogs indicated that during esmolol infusions the concentration ratio of (-)-esmolol/(+)-esmolol was approximately 0.85. After termination of the esmolol infusion the (-)/(+) concentration ratio continuously decreased until (-)-esmolol was no longer quantifiable. These results indicate that stereoselective hydrolysis of esmolol occurs in vitro and in vivo. PMID- 2900736 TI - Metabolism and disposition of n-butyl acrylate in male Fischer rats. AB - Butyl acrylate (BA) is one of the major monomers used in the manufacture of polymers and resins. Because little is known regarding its metabolic fate in animals, it was of interest to study the metabolism and disposition of BA in the rat. After oral administration, butyl [2,3-14C]acrylate was rapidly absorbed and metabolized. The acrylate moiety was metabolized primarily to CO2, accounting for elimination of up to 75% of the administered radiolabel. Elimination in urine and feces accounted for approximately 10 and 2% of the dose, respectively. Initial clearance of radioactivity from the tissues was very rapid and then decreased to a negligible rate 2 hr after iv administration. Total radioactivity in the major tissues was relatively constant from 2 to 24 hr. The majority of the radioactivity in the blood at 24 hr was found to be covalently bound to the protein fraction of the red blood cell membranes. There was some evidence of a first-pass effect when BA was administered by gavage because iv administration resulted in less metabolism to CO2 and quantitative differences in urinary metabolites. The two major metabolites in urine were identified as N-acetyl-S-(2 carboxyethyl)cysteine and N-acetyl-S-(2-carboxyethyl)cysteine-S-oxide. Results of this study indicated that the major portion of a BA dose was hydrolyzed to acrylic acid, which was further metabolized to compounds available for oxidative metabolism. Radiolabeled carbons from the BA molecule were excreted as CO2 or incorporated in trace amounts into lipids, proteins, and other products of de novo synthesis. A smaller portion of the BA dose was conjugated with endogenous glutathione.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900737 TI - Methyl carbamate. Species-dependent variations in metabolism and clearance in rats and mice. AB - Studies of the chronic toxicity and carcinogenicity of methyl carbamate (MC) in F344 rats and B6C3F1 mice indicate that this compound is more toxic to rats than mice. MC was also a carcinogen for rats but not a carcinogen for mice even when administered at a higher dose. The present study of the comparative metabolism and disposition of MC in these two species was conducted to determine possible sources of these varying responses. Results of this study indicate that, although the initial distribution of MC in the two species is similar, the mouse metabolizes and clears MC much more rapidly than does the rat. In the mouse, clearance was primarily by metabolism to CO2 and elimination in exhaled air, which accounted for approximately 70% of the dose in 48 hr. On the other hand, the rat eliminated approximately 18% of the dose as CO2 in 48 hr and a similar amount in urine. The parent compound accounted for approximately 90% of the material excreted in urine of both rats and mice. Only the parent compound was detected in tissues of either species. Less than 4% of the dose was excreted in feces of either species. The lesser ability of the rat to metabolize and eliminate MC as CO2 results in bioaccumulation of this compound on repeat exposure. Therefore, bioaccumulation of MC by the rat on chronic exposure probably results in both greater total exposure and higher peak exposure of most rat tissues vs. those of mice and may thus account for the greater toxicity and possibly carcinogenicity of MC to rats. PMID- 2900738 TI - Mechanism of azoreduction of dimethylaminoazobenzene by rat liver NADPH cytochrome P-450 reductase and partially purified cytochrome P-450. Oxygen and carbon monoxide sensitivity and stimulation by FAD and FMN. AB - We have reported that the hepatocarcinogen dimethylaminoazobenzene (DAB) is reduced by rat liver microsomes in an oxygen- and carbon monoxide-insensitive manner and that activity is induced by clofibrate but no other recognized inducers of cytochrome P-450 activity. In the present study we have shown that the reaction proceeds in a partially purified reconstituted cytochrome P-450 system as well as with purified NADPH-cytochrome P-450 reductase alone. In the latter system, activity is totally inhibited in air whereas the former system is active in air as well as in a carbon monoxide atmosphere. Although clofibrate induces both DAB azoreductase and laurate hydroxylase activities, the suicide substrate 10-undecynoic acid blocks the latter but not the former, implying catalysis by distinct enzymes. FAD and FMN stimulate DAB azoreduction 40-50-fold by both NADPH-cytochrome P-450 reductase alone and by the reconstituted cytochrome P-450 system. However, it was shown that these flavins facilitate electron flow to DAB only from reductase and not from cytochrome P-450. The fact that the reconstituted system, which contains NADPH-cytochrome P-450 reductase, is oxygen insensitive suggests that there is an obligatory electron flow through cytochrome P-450 to DAB, bypassing the oxygen-sensitive step. PMID- 2900739 TI - Metabolism of 1-chloro-2-methylpropene. Evidence for reactive chloroaldehyde intermediates. AB - Recent metabolism and disposition studies of 1-chloro-2-methylpropene (dimethylvinyl chloride) revealed cysteine and N-acetylcysteine conjugates of 3 chloro-2-methylpropenoic acid as the major metabolites. In the present studies we have investigated various steps in the metabolic pathway to determine which step was responsible for the observed trans (E)-stereochemistry of these metabolites. In vitro incubation studies of dimethylvinyl chloride with rat liver microsomes indicated cytochrome P-450-catalyzed aliphatic hydroxylation to be only stereoselective. Both (E)- and (Z)-3-chloro-2-methylpropenols formed in an identical ratio of 2:1 in incubations with microsomes from untreated male and female rats and phenobarbital-treated male rats. No alcohol formation was observed in incubations using microsomes from beta-naphthoflavone-treated male rats. Investigation of the subsequent conjugation reactions of sulfur nucleophiles with haloenoic carbonyl compounds showed that both (E)- and (Z)-3 chloro-2-methylpropenals reacted rapidly with N-acetylcysteine, the E-adduct being the sole product in either case. In contrast, the Michael reaction of the corresponding acids with N-acetylcysteine was very sluggish. Also, whereas the E acid yielded exclusively the corresponding E-adduct, the Z-isomer afforded both Z and E-conjugates in the ratio of 3:4. Glutathione S-transferases had poor activity towards conjugation of glutathione with these acids. Formation of only an E-glutathione conjugate could be observed from either the E- or Z-acid in these enzymatic reactions. Direct Michael reaction of glutathione with (E)-3 bromo-2-methylpropenoic acid, used in chemical synthesis of the conjugates, yielded both the E- and Z-adducts in the ratio of 95:5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900740 TI - Determination and metabolism of dithiol chelating agents. III. Formation of oxidized metabolites of 2,3-dimercaptopropane-1-sulfonic acid in rabbit. AB - Disulfide metabolites of 2,3-dimercaptopropane-1-sulfonic acid (DMPS), a heavy metal chelating agent, have been found in the urine of catheterized rabbits after a single dose of DMPS. After treating the urine with a reducing agent such as NaBH4, a 20-fold increase in DMPS was observed within 6 hr after administration. This suggested the presence of disulfide metabolites of DMPS. The disulfide metabolites were isolated from urine by extraction and were further purified by ion-interaction reverse phase HPLC. Upon reduction with NaBH4 or dithiothreitol, the isolated disulfides converted to DMPS. The isolated metabolites were not chelates of copper or zinc as determined by atomic absorption. Negative ion fast atom bombardment mass spectra indicated that the isolated metabolites were cyclic and acyclic polymeric disulfides of DMPS. The cyclic polymeric disulfides consisted of dimeric and trimeric forms of DMPS. One of the acyclic polymeric disulfides was identified as a DMPS dimer. Urinary excretion profiles of rabbits revealed that the majority of the altered DMPS consisted of cyclic and acyclic polymeric disulfides of DMPS. The cyclic disulfides increased with time while the acyclic disulfides decreased with time, suggesting that the acyclic forms are intermediates and oxidize to the cyclic forms. The rapid formation of stable 8 membered cyclic dimeric and 12-membered cyclic trimeric disulfides of DMPS strongly suggests that oxidation-reduction reactions are occurring. Both spontaneous and enzymatic oxidation mechanisms appear to be involved. PMID- 2900741 TI - Disposition of ethanol and its proximate metabolite, acetaldehyde, in the near term pregnant ewe for short term maternal administration of moderate-dose ethanol. AB - The effect of short term maternal ethanol administration on the disposition of ethanol in the ovine maternal-fetal unit was determined. Eleven conscious instrumented near-term pregnant ewes (between 125 and 134 days of gestation; term, 147 days) received 1-hr iv infusion of 1 g of ethanol.kg of maternal body weight-1.day-1 for six days (N = 6 ewes) or an equivalent volume of saline for six days (N = 5 ewes). On the seventh day, the ethanol- and saline-pretreated animals were administered 1 g of ethanol.kg of maternal body weight-1. Ethanol and acetaldehyde concentrations were determined by headspace GLC in maternal blood, fetal blood, and amniotic fluid samples obtained at selected times during the 14-hr study. The data demonstrated that short term maternal administration of once-daily moderate dose ethanol did not produce major changes in the disposition of ethanol and its proximate metabolite, acetaldehyde, in the maternal, fetal, and amniotic fluid compartments during near-term ovine pregnancy. PMID- 2900742 TI - Pharmacokinetics of cannabidiol in dogs. AB - Cannabidiol (CBD) is one of the major nonpsychoactive cannabinoids produced by Cannabis sativa L. Recent studies have shown that CBD has a high protective index, comparable to that of phenobarbital and phenytoin. Because CBD has been reported to possess both anticonvulsant and antiepileptic activity, its pharmacokinetics were studied in dogs after the administration of two iv doses (45 and 90 mg) and one oral dose (180 mg) to dogs. After iv administration, CBD was rapidly distributed, followed by a prolonged elimination. It has a terminal half-life of 9 hr. CBD plasma levels declined in a triphasic fashion. The total body clearance of CBD was 17 liters/hr (after the 45-mg dose) and 16 liters/hr (after the 90-mg dose). This clearance value, after its normalization to blood clearance using mathematical equations, approaches the value of the hepatic blood flow; the extraction ratio in the liver is 0.74. CBD was observed to have a large volume of distribution, approximately 100 liters. In the dose range of 45 to 90 mg, the increase in the AUC was proportional to the dose, a fact that indicates that the pharmacokinetic profile of CBD in this dose range was not dose dependent. In three of the six dogs studied, CBD could not be detected in the plasma after oral administration. In the other three, the oral bioavailability ranged from 13 to 19%. The results of this study show that CBD is barely absorbed after oral administration to dogs. This low bioavailability may be due to a first pass effect. PMID- 2900743 TI - Distribution of [3H]colchicine in brain and spinal cord areas following its intracerebroventricular or intra-spinal cord injection in rats. AB - Intracerebroventricular or intra-spinal cord (at lumbar level) injection of low doses of colchicine leads to irreversible urine retention. To learn whether colchicine induces this effect by diffusing from the sites of injection, we studied, using the above-mentioned routes of administration, the distribution of [3H]colchicine in brain and spinal cord areas as a function of time. The release of [3H]colchicine into the blood and its elimination via the renal route was studied as well. The results of these experiments show that after its intracerebroventricular injection, [3H]colchicine diffuses to brain areas that normally exert a facilitatory or inhibitory action on urine excretion but reaches the lumbar region in only modest amounts (0.02%). On the other hand, after its intra-spinal cord injection, [3H]colchicine remains at the site of injection, where the sacral micturition center is located. This suggests that intracerebroventricular or intra-spinal cord injected colchicine induces urine retention by exerting its action at two different levels of the neuronal pathway that regulates micturition, depending on the site of injection. PMID- 2900744 TI - Biotransformation of organic nitrate esters in vitro by human liver, kidney, intestine, and blood serum. AB - The biotransformation of glycerol trinitrate (GTN), isosorbide dinitrate (ISD), pentaerythritol tetranitrate (PETN), erythritol tetranitrate (ETN), and mannitol hexanitrate (MHN) by extracts from human liver, small intestine mucosa, kidney, and blood serum was investigated. The glutathione-dependent organic nitrate ester reductase activity of the intestinal mucosa was 21, 4, 4, and 2 times higher than the liver activity for ISD, PETN, GTN, and ETN, respectively. The liver enzymatic activity for MHN was 35% higher than the intestinal activity and 56% higher than kidney enzyme activity. The order of increasing enzymatic rates was: ISD = PETN less than GTN less than ETN less than MHN in the intestinal mucosa; ISD less than PETN less than GTN less than ETN less than MHN in the liver; and ISD less than PETN = GTN less than ETN less than MHN in the kidney. Human serum also metabolized these organic nitrates at lower rates than the studied organs. Thus, the serum specific activities were 1/5 for MHN, 1/30 for ETN, 1/40 for GTN, 1/44 for ISD, and 1/2000 for PETN of the activity present in kidney. On the other hand, the activity of human albumin was lower than that of blood serum. The serum and albumin activities were not modified by reduced glutathione or sulfhydryl inhibitors. These results suggest that small intestine may play an important role in the biotransformation of these drugs at their absorption site, after oral administration. They also demonstrate the possible participation of various human tissues in the overall metabolism of organic nitrate esters. PMID- 2900745 TI - Glucuronides of hydroxylated metabolites of amitriptyline and nortriptyline isolated from rat bile. AB - Polar conjugates were isolated from the bile of rats given amitriptyline (AT, unlabeled or labeled with 14C), nortriptyline (NT), or 10-hydroxy (10-OH) derivatives of the drugs. The procedure involved extraction on a column of polystyrene resin, elution with methanol, and separation by preparative TLC followed by reversed phase HPLC. Individual metabolites were characterized by NMR spectroscopy and fast atom bombardment mass spectrometry and by enzymatic or acid deconjugation with subsequent identification of aglycones and glucuronic acid. Conversely, they were compared with conjugates obtained from hydroxy compounds by incubation with rat liver microsomes and UDP-glucuronic acid. Glucuronides isolated from the bile of rats given AT were derived from 2-OH-AT, (E)- and (Z) 10-OH-AT, 2-hydroxy-3-methoxy- (or 3-hydroxy-2-methoxy) AT, 10, 11-(OH)2-AT, and some of the N-demethylated analogues of these compounds. In most cases, 10-OH compounds form two diastereoisomeric glucuronides produced from the enantiomeric alcohols; 10, 11-(OH)2 metabolites occur as cis- and trans-isomers that are conjugated with glucuronic acid. Administration of synthetic (E)- and (Z)-10-OH AT and -NT leads to the excretion of their glucuronides along with conjugates formed after demethylation and/or introduction of a second OH group. NT gives rise to 2-OH-NT glucuronide besides those conjugates derived from (E)-10-OH-NT. No glutathione conjugates could be detected. PMID- 2900746 TI - Influence of a platelet-activating factor antagonist on circulating levels of cyclosporine in the dog. PMID- 2900747 TI - Quantitative metabolic profile of tripelennamine and pyrilamine in the rat. PMID- 2900748 TI - The effect of pindolol on the transport of L-lysine in renal brush border membrane vesicles. PMID- 2900749 TI - Identification of a quaternary ammonium-linked glucuronide of chlorpromazine in the urine of a schizophrenic patient treated with chlorpromazine. PMID- 2900750 TI - Enantioselective formation and disposition of (E)- and (Z)-10 hydroxynortriptyline. PMID- 2900751 TI - Intervention of nitrite in the metabolism of quaternary ammonium compounds. PMID- 2900752 TI - [Vibrational loads of human teeth during grinding with a dental turbine]. PMID- 2900753 TI - [Soldering, microplasma and laser welding of dental alloys]. PMID- 2900754 TI - [Tests on laser-welded or laser-soldered gold and Co/Cr/Mo dental alloys]. PMID- 2900755 TI - [Anti-insulin, proinsulin, pancreatic polypeptide, glucagon and somatostatin antibodies in patients with insulin-dependent diabetes mellitus treated with conventional insulin preparations]. PMID- 2900756 TI - The efficacy of flumazenil versus physostigmine after midazolam-alfentanil anaesthesia in man. AB - The effects of flumazenil and physostigmine were studied in adult surgical patients recovering from midazolam-alfentanil anaesthesia. Thirty-two patients were anaesthetized with midazolam (0.2 mg kg-1 and 0.36-0.66 mg kg-1 h-1 by infusion) and alfentanil (0.15 mg kg-1 and 0.03-0.15 mg kg-1 h-1 by infusion), vecuronium, 50% nitrous oxide in oxygen, intubated and ventilated. The midazolam and alfentanil infusions were stopped at the end of surgery. Residual neuromuscular blockade and ventilatory depression were antagonized and the patients were extubated. In the recovery room, patients received either flumazenil 1 mg or physostigmine 2 mg i.v. over 10 min in a randomized, double blind way. Before and up to 2 h after injection, patients were asked to perform two psychomotor tests. The degree of sedation and orientation in time and space were also determined. Seventeen patients received flumazenil and 15 patients received physostigmine. Before injection all patients were heavily sedated. After flumazenil, patients were fully awake within 6-7 min but sedation recurred 10-20 min later. After physostigmine, the degree of sedation did not change. The difference in the degree of sedation was significant until 30 min after injection. The time-course of test scores and orientation were similar to that of sedation. No serious side-effects or haemodynamic changes were observed after flumazenil. After physostigmine, seven patients had an increase in heart rate to 140 beats min-1 and blood pressure decreased in three patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900758 TI - Alzheimer's disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell contact. AB - The cloned cDNA encoding the rat cognate of the human A4 amyloid precursor protein was isolated from a rat brain library. The predicted primary structure of the 695-amino acid-long protein displays 97% identity to its human homologue shown previously to resemble an integral membrane protein. The protein was detected in rodent brain and muscle by Western blot analysis. Using in situ hybridization and immunocytochemistry on rat brain sections, we discovered that rat amyloidogenic glycoprotein (rAG) and its mRNA are ubiquitously and abundantly expressed in neurons indicating a neuronal original for the amyloid deposits observed in humans with Alzheimer's disease (AD). The protein appears in patches on or near the plasma membranes of neurons suggesting a role for this protein in cell contact. Highest expression was seen in rat brain regions where amyloid is deposited in AD but also in areas which do not contain deposits in AD. Since amyloid deposits are rarely observed in rat brain, we conclude that high expression of AG is not the sole cause of amyloidosis. PMID- 2900757 TI - Primary structure and developmental expression pattern of Hox 3.1, a member of the murine Hox 3 homeobox gene cluster. AB - The murine Hox 3.1 gene maps to a cluster of homeobox-containing genes on chromosome 15. We report the primary structure of the Hox 3.1 protein, as deduced from cDNA sequences, and the expression of Hox 3.1 mRNA during embryogenesis. In addition, a second member of the gene cluster, Hox 3.2, is characterized. The predicted Hox 3.1 protein consists of 242 amino acid residues and has a calculated mol. wt of 28 kd. Besides the homeodomain, it shares with other murine homeodomain proteins a conserved hexapeptide, a region rich in glutamic acid residues at the carboxy terminus and homology at the amino terminus. During embryogenesis, Hox 3.1 transcripts are detected first in the posterior neural tube of 9.5 days post-coital embryos. At later developmental stages, a ventral dorsal gradient of Hox 3.1 transcript accumulation is established. Hox 3.1 transcripts also are detected in the thoracic sclerotomes from the 6th to the 10th thoracic pre-vertebrae. The data support the hypothesis that the Hox 3.1 gene specifies positional information during murine embryogenesis. PMID- 2900759 TI - Processing at immunoglobulin polyadenylation sites in lymphoid cell extracts. AB - We have developed an in vitro system for polyadenylation of RNA substrates in cell-free nuclear extracts prepared from murine cells of lymphoid origin. RNA substrates containing the adenovirus L3, murine immunoglobulin (IgM) secreted and membrane polyadenylation sites were accurately polyadenylated in these extracts. Kinetic analysis showed that the rate of polyadenylation in vitro responds proportionally to the substrate concentration. Quantitation of the initial rate of polyadenylation at the three sites permitted comparison of the activities of extracts prepared from HeLa cells, B cells (Wehi 231) and plasmacytoma cells (P9.37.11). From this analysis, we concluded that in all three extracts the polyadenylation activity at the L3 site was higher than that of either of the IgM sites. In contrast to the preferential utilization of the secreted site in vivo in plasmacytomas, this site was not selectively processed in plasmacytoma as compared to B cell extracts. The efficiency of polyadenylation at both IgM sites in the plasmacytoma extract was significantly lower than that in the B cell extract. The common low activity at the IgM sites in the plasmacytoma cell extract suggests that the rate-limiting step for polyadenylation at these two sites differs from that at the L3 site. PMID- 2900760 TI - The mouse ribosomal gene terminator consists of three functionally separable sequence elements. AB - The structural requirements for 3' end formation of mouse pre-rRNA have been studied. Three sequence elements are shown to be required for accurate and efficient transcription termination by RNA polymerase I (pol I) assayed both in a cell-free transcription system and in vivo after transfection of rDNA minigene constructs into 3T6 cells. The essential termination signal is the previously identified 18-bp conserved element (AGGTCGACCAGATTANTCCG) that contains a SalI restriction site. This sequence motif (the 'Sal box') interacts with a specific nuclear protein that directs transcription termination. Here we demonstrate that the 'Sal box' sequence motif is sufficient for termination of pol I transcripts and the release of the nascent RNA chains from the template. However, in addition to this termination signal, pyrimidine-rich sequences flanking the box at the 5' and 3' side play a role in the efficient and correct formation of authentic pre rRNA termini. Downstream sequences contribute to the efficiency of the termination reaction, whereas the position of 3' end formation (i.e. 21 bp upstream of the 'Sal box') is affected by 5' flanking regions. These flanking regions are recognized by at least two different nuclear factors which specifically bind to DNA sequences located upstream and downstream of the 'Sal box'. PMID- 2900761 TI - Four mating-type genes control sexual differentiation in the fission yeast. AB - The mating-type region of fission yeast consists of three components, mat1, mat2 P and mat3-M, each separated by 15 kb. Cell-type is determined by the alternate allele present at mat1, either P in an h+ or M in an h- cell. mat2-P and mat3-M serve as donors of information that is transposed to mat1 during a switch of mating type. We have determined the nucleotide sequence of each component of mat. The P and M specific regions are 1104 and 1128 bp, respectively, and bounded by sequences common to each mating-type cassette (H1; 59 bp and H2; 135 bp). A third sequence is present at mat2-P and mat3-M but absent at mat1 (H3; 57 bp), and may be involved in transcriptional repression of these cassettes. mat1-P and mat1-M each encode two genes (Pc; 118 amino acids, Pi; 159 amino acids, Mc; 181 amino acids and Mi; 42 amino acids). Introduction of opal or frame-shift mutations into the open-reading-frame of each gene revealed that Pc and Mc are necessary and sufficient for mating and confer an h+ or h- mating type respectively. All four genes are required for meiotic competence in an h+/h- diploid. The transcription of each mat gene is strongly influenced by nutritional conditions and full induction was observed only in nitrogen-free medium. The predicted product of the Pi gene contains a region of homology with the homeobox sequence, suggesting that this gene encodes a DNA binding protein that directly regulates the expression of other genes. PMID- 2900762 TI - Molecular analysis of formaldehyde-induced mutations in human lymphoblasts and E. coli. AB - The molecular nature of formaldehyde (HCHO)-induced mutations was studied in both human lymphoblasts and E. coli. Thirty HPRT- human lymphoblast colonies induced by eight repetitive 150 microM HCHO treatments were characterized by Southern blot analysis. Fourteen of these mutants (47%) had visible deletions of some or all of the X-linked HPRT bands, indicating that HCHO can induce large losses of DNA in human lymphoblasts. In E. coli, DNA alterations induced by HCHO were characterized with use of the xanthine guanine phosphoribosyl transferase (gpt) gene as the genetic target. Exposure of E. coli to 4 mM HCHO for 1 hr induced large insertions (41%), large deletions (18%), and point mutations (41%). Dideoxy DNA sequencing revealed that most of the point mutations were transversions at GC base pairs. In contrast, exposure of E. coli to 40 mM HCHO for 1 hr produced 92% point mutations, 62% of which were transitions at a single AT base pair in the gene. Therefore, HCHO is capable of producing different genetic alterations in E. coli at different concentrations, suggesting fundamental differences in the mutagenic mechanisms operating at the two concentrations used. Naked pSV2gpt plasmid DNA was exposed to 3.3 or 10 mM HCHO and transformed into E. coli. Most of the resulting mutations were frameshifts, again suggesting a different mutagenic mechanism. PMID- 2900763 TI - Bordetella pertussis adenylate cyclase. Penetration into host cells. AB - Exposure of Chinese hamster ovary, mouse adrenal cortex tumor (Y-1), THP-1 and U 937 cells and human erythrocytes to adenylate-cyclase-containing urea extracts of Bordetella pertussis (strain 114) organisms promotes the formation of large concentrations of intracellular cAMP. Accumulation is dependent on dose and temperature, with significant accumulation occurring at 4 degrees C, and is virtually instantaneous, with a doubling at 1 min. There is an absolute Ca2+ requirement but external calmodulin (the activator of cyclase activity) has no effect except in erythrocytes and U-937 cells, where it reduces cAMP accumulation. However, calmodulin antagonists inhibit cAMP accumulation. In Y-1 adrenal cells the urea-extract adenylate cyclase stimulates steroidogenesis. Anti (B. pertussis) antibodies inhibit cyclase activity and prevent further cAMP accumulation after 10 min in cells previously exposed to urea extract. The same effect is obtained by washing. This suggests that a portion of the cyclase is associated with cells in a form not accessible to antibody or washing but accessible to substrate, which we interpret as internalized enzyme with a short lifetime. Continuing cAMP accumulation thus appears to need a continuing source of external cyclase. Inhibitors of the effect of diphtheria toxin, such as NH4Cl, methylamine, chloroquine or monensin, have no inhibitory effect on the accumulation of intracellular cAMP promoted by the internalized adenylate cyclase of urea extracts of B. pertussis organisms. We conclude that entry of the cyclase into cells is not by receptor-mediated endocytosis. PMID- 2900764 TI - Effect of intracellular pH and potassium ions on a primary transport system for glutamate/aspartate in Streptococcus mutans. AB - We have studied the mechanism of L-glutamate/L-aspartate transport in a fermentative oral bacterium of Streptococcus mutans (strain Ingbritt). The transport rate stays virtually constant throughout the pH range 5.5-8.5 and followed Michaelis-Menten type kinetics. At high pH values from 7 to 8.5, transport was essentially insensitive to N,N'-dicyclohexyl-carbodiimide (DCCD), an inhibitor of ATPase, and to carbonyl cyanide-p-trifluoromethoxyphenyl hydrazone (FCCP), an ionophore dissipating proton motive force indicating that S. mutans transports glutamate by a primary transport system at the expense of ATP or an alternative energized metabolite. At lower external pH (7-5.5), DCCD (100 microM) or FCCP (10 microM) significantly inhibited L-glutamate transport while the intracellular ATP level was hardly affected, indicating that the activity of the primary transport system was decreased at lower intracellular pH. The glutamate transport was stimulated in the presence of potassium ion at an external pH of 6. The stimulation can be explained partly by the regulation of intracellular pH with concomitant potassium ion movement. PMID- 2900765 TI - 8-Bromo cyclic GMP mimics the actions of nitroglycerin in modulating responses produced by full and partial alpha-adrenoceptor agonists in canine saphenous vein. AB - The purpose of the present study was to determine whether 8-bromo cyclic GMP (8 Br cGMP) mimics the actions of nitroglycerin (GTN) in inhibiting alpha-1 versus alpha-2 adrenoceptor-mediated constrictor responses in canine saphenous vein. Phenylephrine (PE) and L-dobutamine were used as full and partial alpha-1 adrenoceptor agonists, respectively, and B-HT 920 was employed as a selective alpha-2 adrenoceptor agonist. The ability of 8-Br cGMP and GTN to inhibit vasoconstrictor responses to a standard agonist concentration of PE, L-dobutamine and B-HT 920 was determined. 8-Br cGMP like GTN produced a selective antagonism of alpha-2-mediated responses of B-HT 920 and had minimal effects on alpha-1 induced constrictor responses of phenylephrine. However, when a portion of the alpha-1-adrenoceptor pool was inactivated by phenoxybenzamine (POB) (5 x 10(-8) M, 1 x 10(-7) M) 8-Br cGMP like GTN produced a significant depression of responses to PE. In addition, contractions produced by L-dobutamine, a selective partial alpha-1 adrenoceptor agonist (no alpha receptor reserve), were highly sensitive to inhibition by 8-Br cGMP and GTN. These results suggest that the presence of a large alpha-1-adrenoceptor reserve to PE concealed an underlying functional antagonism to alpha-1-adrenoceptor-mediated responses by GTN and 8-Br cGMP. The similarity in the efficacy and potency of these two agents (8-Br cGMP and GTN) suggests that the effects of GTN in canine saphenous vein may be the result of an increase in the intracellular concentration of cGMP. PMID- 2900766 TI - Explanation of the discrepancy between the degree of organic nitrate decomposition, nitrite formation and guanylate cyclase stimulation. AB - We continuously studied the quantitative formation of nitric oxide (NO), nitrite and nitrate ions from several organic nitrate esters in the presence of various thiol-containing compounds by spectroscopy and HPLC. The results indicate that there are different pathways of decomposition depending on the chemical nature of the mercaptan tested. The amino acid cysteine is known to function as an essential cofactor for guanylate cyclase activation by organic nitrates in vitro. For comparison we investigated several structural analogues with respect to their nitric oxide or nitrite ion releasing potency. Both were found to represent the main products resulting from nitrate ester breakdown besides the respective alcohols. We found that only those compounds were able to activate the enzyme in the presence of nitroglycerin (GTN) which induce the release of NO as well. On the other hand, nearly all other thiols tested caused an in vitro decomposition of organic nitrates by producing excess nitrite and the corresponding disulfide without the formation of NO. Thus, the decomposition of organic nitrates to nitrite ions does not contribute at all to activation of guanylate cyclase. Our results confirm that the liberation of nitric oxide is the common principle of action for all nitrovasodilators. In addition, our results suggest that the thiol consuming transformation of organic nitrates into nitrite ions (ratio NO/nitrite 1:10) may lead to a depletion of cysteine stores, resulting in a decreased formation of NO and, consequently, in a decrease of guanylate cyclase activation, clinically arising as nitrate tolerance. PMID- 2900767 TI - Problems encountered using temazepam syrup for sedation in infants. AB - Six infants with a history of wheezing were given temazepam syrup as sedation, to allow lung function tests to be performed. Despite doses ranging from 2.5 mg/kg 4.5 mg/kg only one infant remained a sleep for 1 h, the time taken for full lung function to be assessed. All other infants awoke within 15 min before test could be completed. Three infants developed hiccoughs and three were very irritable after awaking from sedation. PMID- 2900768 TI - Spinal subarachnoid injection of somatostatin causes neurological deficits and neuronal injury in rats. AB - The tetradecapeptide somatostatin produced dose-related neurological deficits following subarachnoid injection in the lumbar spinal cords of rats. Lower pharmacological doses (1.6 and 3.1 nmol, i.t.) of somatostatin caused only transient deficits, while higher doses (6.2-25 nmol, i.t.) caused persistent deficits characterized by motor and sensory impairments in hindlimbs and tail, hindlimb edema, priapism, bladder atony with infarction, and urinary incontinence. Pretreatment with 0.3 nmol of the somatostatin receptor antagonist cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)] blocked the hindlimb paralytic effects of 3.1 and 6.2 nmol of somatostatin, and significantly improved neurological recovery injection of 12.5 nmol of somatostatin. Higher doses of the antagonist produced hindlimb paralysis by itself. Neuroanatomical evaluations revealed extensive cell loss and necrosis in the lumbosacral spinal cords of rats paralyzed by 25 nmol of somatostatin. Collectively, these results suggest that through interactions with a receptor, somatostatin destroys neurons involved in diverse spinal cord functions. PMID- 2900769 TI - Essential fatty acids modulate apomorphine activity at dopamine receptors in cat caudate slices. AB - We have used a classical neurotransmitter release model to investigate the effect of dietary polyenoic fatty acids on the sensitivity of the presynaptic dopamine autoreceptor in slices of cat caudate nucleus. Maximum inhibition of [3H]dopamine release was seen only in animals fed a diet containing post delta-6-desaturation fatty acids of both the w3 and w6 series. The removal of either or both groups of fatty acids resulted in attenuation of sensitivity of the autoreceptor to apomorphine. We propose that a balance of w3 and w6 fatty acids is required to maintain normal dopaminergic function in the cat caudate nucleus. PMID- 2900770 TI - Presence of dopamine-dependent adenylate cyclase activity in human renal cortex. AB - The effects of dopamine (DA) and of two selective DA DA1 agonists (SKF 38393 and SKF 82526) on adenylate cyclase activity were studied with human kidney cortex membrane preparations. DA elicited a dose-related stimulation of adenylate cyclase activity with an EC50 of 60 microM. The selective DA DA1 antagonist SCH 23390 behaved as a competitive antagonist, shifting the dose-response curve to the right. The non-selective beta-adrenoceptor antagonist (-)-propranolol did not affect the EC50 of the dose-response curve to DA but attenuated the maximal stimulatory effect of DA at concentrations higher than 100 microM. (+)-Sulpiride inhibited DA-induced adenylate cyclase stimulation in a dose-dependent manner with an IC50 of 4.6 X 10(-8) M but (-)-sulpiride was without effect. Both SKF 38393 and SKF 82526 stimulated the adenylate cyclase activity of human kidney cortex; this effect was completely antagonized by SCH 23390. Our results, demonstrating the presence of DA-sensitive adenylate cyclase activity, strongly suggest the presence of a DA receptor of the DA1 subtype in human kidney cortex. PMID- 2900771 TI - Coexistence of somatostatin-immunoreactivity in an adrenal pheochromocytoma and a thyroid medullary carcinoma (Sipple syndrome). AB - The presence of somatostatin-immunoreactivity in tumor tissue of adrenal pheochromocytoma and thyroid medullary carcinoma identified by peroxidase antiperoxidase technique is reported in one case of Sipple syndrome. This patient was found to have a high concentration of somatostatin-immunoreactivity in the peripheral blood (40 ng/l, normal 0-20 ng/l). After removal of the tumors, the plasma somatostatin-immunoreactivity fell within normal range (12.5 ng/l). This seems to be the first report of Sipple syndrome that produces somatostatin immunoreactivity in both: pheochromocytoma and thyroid medullary carcinoma. PMID- 2900772 TI - The effect of temperature on recombination activity in testes of rodents. AB - An extractable enzyme system capable of catalyzing recombination in vitro was described in murine spermatocytes [Hotta et al. (1985) Chromosoma 93, 140-151]. The system is specific to meiosis, its activity increasing 400-fold between the premeiotic S-phase and mid-pachytene. The present study examines the effect of temperature on this system since the elevation of testicular temperature is one of the major factors causing impairment of testicular function. A strong depression of in vitro recombination activity occurred immediately after raising the testicular temperature in vivo by translocating the testes into the abdominal cavity (cryptorchid). The in vitro study also showed that the extract from spermatocytes preferred lower temperatures (30-32 degrees C) than somatic cells (37 degrees C) for maximal activity of recombination. These results suggest that the strong depression of recombination activity may be an important factor which causes degeneration of testes by heat. PMID- 2900773 TI - Direct evidence for the binding of rat liver DPP IV to collagen in vitro. AB - Previous studies have shown that the tripeptide Gly-Pro-Ala, a substrate for dipeptidyl peptidase IV (DPP IV, EC 3.3.14.5), interferes with initial spreading of hepatocytes on a matrix consisting of fibronectin and denatured collagen. In the present investigation we report that the tripeptide as well as the anti-DPP IV antibody inhibits the initial spreading of hepatocytes also on native collagen. This effect appears to be due to the interaction of DPP IV from hepatocyte plasma membrane with native collagen. It is shown in vitro by immunohistochemistry, catalytic histochemistry, and by affinity chromatography of solubilized plasma membrane on collagen-Sepharose that DPP IV has a binding affinity to collagen. This binding does not affect the activity of DPP IV. PMID- 2900774 TI - Acylation and deacylation of phospholipids in isolated bovine rod outer segments. AB - Isolated bovine rod outer segments (ROS) were incubated under different conditions with radiolabeled fatty acid-Coenzyme A (CoA) compounds, fatty acids and phospholipids in order to further investigate the rates, mechanisms and function of phospholipid metabolism within that organelle. ROS contain acyl CoA synthetase, acyl transferase, acyl CoA hydrolase, and phospholipase A activities. Although different radiolabeled fatty acid CoAs were esterified to the major ROS phospholipids (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine) at the same rate, different free fatty acids were esterified at different rates. There was no correlation between these estimates of in vitro rates of incorporation of fatty acids and the fatty acid composition of ROS phospholipids. Both the deacylation of radiolabeled phospholipids (phospholipase A activity) and the acylation of endogenous phospholipids (acyl transferase activity) were maximally stimulated when ATP, CoA, Mg2+ and Ca2+ were present, and both processes were stimulated by pro-oxidizing conditions and exposure to light. Under phospholipase A-stimulatory conditions, there was preferential hydrolysis of polyenoic fatty acids from endogenous ROS phospholipids. Both the acylation and deacylation reactions were primarily at the sn-2 position of ROS phospholipids. PMID- 2900775 TI - Selective failure of long-term survival of isolated photoreceptors from both homozygous and heterozygous rd (retinal degeneration) mice. AB - Retinas from homozygous rdle/rdle and heterozygous rdle/++ C57BL/6J mice were dissected and dissociated on postnatal day 2, when they are still essentially indistinguishable. The resulting cell suspensions were seeded on highly adhesive substrata, to which the cells attach as individual units, and grown in vitro for 2 weeks in serum-free, chemically defined media. The behavior of neurons and photoreceptors in vitro was investigated with several techniques; essentially no differences were found between rdle/rdle and rdle/++ cells. Three distinctive cell types could be recognized in cultures of both genotypes towards the end of the first week in vitro: process-free cells, multipolar neurons and rod photoreceptors. There were similarities between rdle/rdle and rdle/++ cultures in the number and morphology of photoreceptor cells, to include the presence of a cilium and a short neurite terminating in a spherule-like body. Moreover, in cultures of both genotypes, only photoreceptors showed opsin immunoreactivity and the antigen recognized by the rod-specific monoclonal antibody RET-P1. Biochemical and autoradiographic studies demonstrated that rdle/rdle and rdle/++ cells also showed similar uptakes of the putative amino acid neurotransmitters glutamate and aspartate (associated with most of the photoreceptors and only some neurons), and gamma-aminobutyric acid (associated with neurons but absent in photoreceptors). Thus, according to several parameters, the properties shown by photoreceptor cells were similar in rdle/rdle and rdle/++ cultures during the first week in vitro. Massive photoreceptor cell death was observed in both genotypes during the second week in vitro, coinciding with the time when photoreceptor degeneration occurs in vivo in rd/rd, but not in rd/+ retinas. Photoreceptor death in culture appeared to be specific, since approx. 80% of the non-photoreceptor neurons survived normally during the period when photoreceptor degeneration took place. Several reports from the literature suggest that the period around postnatal days 8-10 represents a critical stage for rd/rd photoreceptors, since they survive until this time but degenerate thereafter. Genetically normal photoreceptors apparently undergo a comparable crisis during maintenance in primary culture, suggesting the involvement of cell-cell contacts and/or retina-derived environmental signals in the survival or rod visual cells. PMID- 2900776 TI - Fine structure histochemical study of the distribution of dipeptidylpeptidase IV (DPP IV) in the meningeal lamellae of the rat. AB - DPP IV was localized in the meningeal lamellae of the spinal cord sheaths of the rat by light and electron microscopy. A membrane-bound reaction product of DPP IV was found in the internal, intermediate and external meningeal lamellae which delineated the CSF-filled meningeal spaces. The cells of the marginal glia displayed heterogeneous localization of the reaction product for DPP IV. DPP IV distribution in the spinal cord sheaths suggests its possible participation in the interactions of the meningeal cells with the neuropeptides in cerebrospinal fluid. PMID- 2900777 TI - [Evaluation of the immunotoxicity of sulfanilamide, anti-inflammatory and antihistaminic preparations]. AB - The effects of 15 widely used drugs on the production of IgE-antibodies and the development of anaphylactic sensitization of rat skin were studied. Some drugs were shown to be able to increasing antibody titres in the blood and prolonging skin sensitization. PMID- 2900778 TI - Three adenine nucleotide binding sites in F1-F0 mitochondrial ATPase as revealed by presteady-state and steady-state kinetics of ATP hydrolysis. Evidence for two inhibitory ADP-specific noncatalytic sites. AB - Preincubation of submitochondrial particles with ADP in the presence of Mg2+ results in the complete inhibition of ATPase which is slowly reactivated in the assay mixture containing ATP and the ATP regenerating system. Significantly, the rate of activation increases as the concentration of ADP in the preincubation mixture rises from 1 microM to 20 microM and reaches a constant value at higher ADP concentrations. The first-order rate constant for the activation process in the assay mixture is ATP-dependent at any level of inhibitory ADP. The data obtained strongly suggest that two ADP-specific inhibitory sites and one ATP specific hydrolytic site are present in F1-F0 ATPase. Taking into account the (3 alpha.3 beta).gamma.delta.epsilon structure of F1, it is concluded that the synchronous discharge of ADP from two inhibitory sites during the activation occurs after ATP binds to the ATPase catalytic site. PMID- 2900779 TI - Studies on the import into mitochondria of yeast ATP synthase subunits 8 and 9 encoded by artificial nuclear genes. AB - Direct fusions have been constructed between each of subunits 8 and 9 from mitochondrial ATPase of Saccharomyces cerevisiae, proteins normally encoded inside mitochondria, and the cleavable N-terminal transit peptide from the nuclearly encoded precursor to subunit 9 of Neurospora crassa mitochondrial ATPase. The subunit 8 construct was imported efficiently into isolated yeast mitochondria and was processed at or very near the fusion point. When expressed in vivo from its artificial nuclear gene, this cytoplasmically synthesized form of subunit 8 restored the growth defects of aap 1 mutants unable to produce subunit 8 inside the mitochondria. The subunit 9 construct was, however, unable to be imported into isolated mitochondria and could not, following nuclear expression in vivo, complement growth defects in mitochondrial oli 1 mutants. This behaviour is contrasted with the previously demonstrated import competence of another yeast subunit 9 fusion, bearing the first five residues of mature N. crassa subunit 9 interposed between its own transit peptide and the yeast subunit 9 moiety. PMID- 2900780 TI - [Organization at feldsher-midwife centers of medical and social care for single elderly persons]. PMID- 2900781 TI - [The role of the feldsher in fighting drug abuse]. PMID- 2900782 TI - Multiple endocrine neoplasia--type I syndrome and hyperprolactinemia. PMID- 2900783 TI - [Mechanisms of the regulation of immunologic memory]. PMID- 2900784 TI - [The role of glucagon, somatostatin and somatotropin in the physiological regulation of carbohydrate balance]. PMID- 2900785 TI - [Effect of beta-adrenoactive substances on the secretory function of the stomach]. PMID- 2900786 TI - [Alternative metal bonding. Composite cement for durable bond]. PMID- 2900787 TI - [Insufficient filling, casting and gas-inclusion solders are also unsafe due to existing diffusion]. PMID- 2900788 TI - Regulation of glycogenolysis by neurotransmitters in the central nervous system. AB - Neurotransmitters are the molecules that neurons use to communicate with each other and with the other cell types of the nervous system, such as glial cells and cells of the vasculature. The best characterized actions of neurotransmitters are the alterations in excitability that they elicit in other neurons. These changes in neuronal firing rate are due to the opening or closing of transmembrane channels selectively permeable to given ionic species. We have however recently demonstrated that certain neurotransmitters can regulate energy metabolism within discrete regions of the central nervous system. In particular we have observed that Vasoactive Intestinal Peptide stimulates glycogenolysis in the cerebral cortex. This action is also exerted by the monoamines noradrenaline, serotonin and histamine. Studies in primary cultures indicate that the glycogenolysis elicited by neurotransmitters may take place in astrocytes, which are glial cells and where glycogen is predominantly stored in the nervous system. These observations suggest that the primary function of certain neuronal circuits may be to regulate the availability of energy substrates within discrete neuronal ensembles. PMID- 2900789 TI - [Does somatostatin have a role in the treatment of diabetes?]. PMID- 2900790 TI - [A method for determining the error rate in evaluating the size of a test object]. PMID- 2900791 TI - Calcitonin gene-related peptides I and II and calcitonin: distinct effects on gastric acid secretion in humans. AB - The human calcitonin gene-related peptides I and II (CGRP I and CGRP II) are two neuropeptides that have been recognized throughout the gastrointestinal system including the stomach. The present study was undertaken to compare in healthy volunteers the effects of intravenous infusions of CGRP I and CGRP II (79 pmol/kg.h) on pentagastrin-stimulated acid secretion to those of calcitonin (88 pmol/kg.h). Calcitonin gene-related peptide I did not inhibit basal or pentagastrin-stimulated acid secretion. However, CGRP II and calcitonin inhibited pentagastrin-stimulated acid responses by 20% and 28%, respectively (p less than 0.05 and p less than 0.01), whereas basal acid output was only reduced with calcitonin (p less than 0.05). These effects were recognized with low doses of pentagastrin, and absent with high doses suggesting competitive inhibition. Furthermore, step-doses of CGRP I and CGRP II (79-320 pmol/kg.h) were given intravenously on continuous pentagastrin stimulation and compared with calcitonin (88-352 pmol/kg.h). Calcitonin gene-related peptide II and calcitonin induced a dose-dependent decrease of acid output, whereas CGRP I was ineffective. The inhibitory effects of CGRP II and calcitonin are not due to increased gastric alkaline secretion or to somatostatin release, as neither peptide stimulated gastric bicarbonate secretion or induced an increase in circulating somatostatin. In conclusion, CGRP II, unlike CGRP I, inhibits gastric acid secretion in humans. Inhibitory effects of CGRP II and of calcitonin were comparable. The results imply that CGRP I and II, at the level of the stomach, have distinct biological properties in humans. PMID- 2900792 TI - Calcitonin gene-related peptide: enteric and cardiovascular effects in the dog. AB - We have measured the effects of intravenous infusion of calcitonin gene-related peptide at doses of 2.5, 10, and 50 pmol/kg.min on net jejunal water and solute fluxes and on plasma somatostatin concentrations in dogs. The hemodynamic effects and the pharmacokinetics of the peptide were also assessed. Using the triple lumen perfusion technique in unsedated restrained animals it was shown that the highest dose of the peptide stimulated a transient net jejunal water and electrolyte secretion, and induced diarrhea in 4 of 6 animals receiving it. The peptide also induced dose-dependent tachycardia, hypotension, and increases in plasma immunoreactive somatostatin. All three doses of calcitonin gene-related peptide produced plasma immunoreactive peptide levels within the elevated range previously measured in human patients with medullary thyroid carcinoma. Calcitonin gene-related peptide may have a major role in the pathogenesis of secretory diarrhea in medullary thyroid carcinoma. PMID- 2900793 TI - Effects of chromosomal inversion on cell fitness in Escherichia coli K-12. AB - In an effort to learn what factors might mitigate the establishment of Escherichia coli variants bearing major chromosomal rearrangements, we have examined the effects on cell growth of two inversions between rRNA operons. One of these inversions, IN(rrnD-rrnE), had been propagated in a commonly used subline of E. coli K-12 for approximately 30 yr before its discovery, a fact that illustrates the absence of obvious detrimental effects associated with the inversion. We found that culturing under conditions requiring repeated transition from stationary phase to rapid growth led to the replacement of IN(rrnD-rrnE) cells by cells that had undergone either of two types of additional chromosomal inversion: one type fully restored the wild-type order, while the other partially restored it. The partial reinversion was also between rrn operons, but it left a small transposition. The tendency for overgrowth by these revertants persisted through several rounds of periodic selection. In contrast, the other inversion, IN(rrnG-rrnE), was associated with severe, detrimental effects. The effects of IN(rrnG-rrnE) were also alleviated by full or partial reinversion. The probable relationship between the severity of the effects caused by the inversions and the degree of displacement of the replication origin is discussed. Spontaneous inversion events between rrn operons separated by 18% of the chromosome were estimated to occur at a frequency of roughly 10(-5). If extended to natural situations, the growth disadvantage together with the relatively high frequency of reinversion suggest that clones of cells with an inversion between these rrn operons would be readily overgrown by revertants. PMID- 2900795 TI - Linkage disequilibrium in human ribosomal genes: implications for multigene family evolution. AB - Members of the rDNA multigene family within a species do not evolve independently, rather, they evolve together in a concerted fashion. Between species, however, each multigene family does evolve independently indicating that mechanisms exist which will amplify and fix new mutations both within populations and within species. In order to evaluate the possible mechanisms by which mutation, amplification and fixation occur we have determined the level of linkage disequilibrium between two polymorphic sites in human ribosomal genes in five racial groups and among individuals within two of these groups. The marked linkage disequilibrium we observe within individuals suggests that sister chromatid exchanges are much more important than homologous or nonhomologous recombination events in the concerted evolution of the rDNA family and further that recent models of molecular drive may not apply to the evolution of the rDNA multigene family. PMID- 2900794 TI - The rosy region of Drosophila melanogaster and Drosophila simulans. I. Contrasting levels of naturally occurring DNA restriction map variation and divergence. AB - A 40-kb region around the rosy and snake loci was analyzed for restriction map variation among 60 lines of Drosophila melanogaster and 30 lines of Drosophila simulans collected together at a single locality in Raleigh, North Carolina. DNA sequence variation in D. simulans was estimated to be 6.3 times greater than in D. melanogaster (heterozygosities per nucleotide of 1.9% vs. 0.3%). This result stands in marked contrast to results of studies of phenotypic variation including proteins (allozymes), morphology and chromosome arrangements which are generally less variable and less geographically differentiated in D. simulans. Intraspecific polymorphism is not distributed uniformly over the 40-kb region. The level of heterozygosity per nucleotide varies more than 12-fold across the region in D. simulans, being highest over the hsc2 gene. Similar, though less extreme, variation in heterozygosity is also observed in D. melanogaster. Average interspecific divergence (corrected for intraspecific polymorphism) averaged 3.8%. The pattern of interspecific divergence over the 40-kb region shows some disparities with the spatial distribution of intraspecific variation, but is generally consistent with selective neutrality predictions: the most polymorphic regions within species are generally the most divergent between species. Sequence length polymorphism is observed for D. melanogaster to be at levels comparable to other gene regions in this species. In contrast, no sequence length variation was observed among D. simulans chromosomes (limit of resolution approximately 100 bp). These data indicate that transposable elements play at best a minor role in the generation of naturally occurring genetic variation in D. simulans compared to D. melanogaster. We hypothesize that differences in species effective population size are the major determinant of the contrasting levels and patterns of DNA sequence and insertion/deletion variation that we report here and the patterns of allozyme and morphological variation and differentiation reported by other workers for these two species. PMID- 2900796 TI - Cloning and sequencing of rhesus monkey pepsinogen A cDNA. AB - The complete nucleotide sequence of Rhesus monkey (Macaca mulatta) pepsinogen A (PGA) cDNA was determined from two partially overlapping cDNA clones, covering the whole coding sequence and part of the flanking sequences. The nucleotide and deduced amino acid sequences were compared to known PGA sequences from other species. The degree of similarity with human PGA appeared to be 96% at the nucleotide sequence level and 94% at the amino acid sequence level. In the coding region the divergence was highest in the activation peptide. The amino acid sequence similarity between Japanese monkey (Macaca fuscata) PGA and Rhesus monkey PGA was shown to be 99%. Using the cDNA as probe in Southern hybridization of EcoRI-digested human and Rhesus monkey genomic DNAs, PGA patterns with inter individual differences were observed. The hybridization patterns are compatible with the existence of a PGA multigene family in both species. PMID- 2900797 TI - Psychoactive drugs in the elderly: antipsychotics and anxiolytics. AB - Psychiatric disorders in the elderly are common and often overlap with multiple medical problems. If used inappropriately, psychotropic drugs can further compromise a difficult clinical situation. Management of elderly patients with agitation, psychosis, anxiety, and insomnia are reviewed with a discussion of the optimal use of antipsychotic, anxiolytic, and sedating drugs. Initial attempts to control symptoms should involve nonpharmacologic techniques, but, when absolutely required, psychotropic drugs will often relieve symptoms with a minimum of side effects. Dangers in the chronic use of neuroleptics are stressed. PMID- 2900798 TI - [Effects of terazosin on the blood pressure responses to tilting in conscious animals: comparison with prazosin]. AB - Inhibitory effects of terazosin on the compensatory blood pressure responses to tilting were studied in conscious rabbits and spontaneously hypertensive rats (SHR). In rabbits, doses which reduced the mean blood pressure by 15 mmHg were 330 micrograms/kg, i.v., for terazosin and 42 micrograms/kg, i.v., for prazosin, while those which depressed the blood pressure responses to tilting by 30 mmHg were 180 micrograms/kg, i.v., for terazosin and 54 micrograms/kg, i.v., for prazosin. In SHR, almost equal decreases in the mean blood pressure (about 30%) were observed by 1 mg/kg prazosin, p.o., 20 mg/kg hexamethonium, i.p., 3 mg/kg hydralazine, p.o., or 3 mg/kg nicardipine, p.o. In these conditions, prazosin and hexamethonium markedly depressed the blood pressure responses to tilting, whereas hydralazine and nicardipine showed little effect. The results with these antihypertensive drugs closely paralleled the established orthostatic profiles seen clinically. In this SHR tilting model, when the mean blood pressure was reduced by 15%, prazosin significantly depressed the tilting reflexes; however, terazosin produced no depression. Considering the dose ratio of terazosin to prazosin for antihypertensive effects and inhibitory effects on the tilting reflexes, the orthostatic liability of terazosin was about 3 times as low as that of prazosin. On the basis of these results, it is expected that terazosin causes less orthostatic hypotension than prazosin in clinical use. PMID- 2900800 TI - Increased frequency of specific alleles of the c-Ha-ras gene in Japanese cancer patients. AB - We have examined the c-Ha-ras locus in 145 cancer patients of a mixed group and 164 normal individuals in Japan for restriction fragment length polymorphisms and compared the allele distributions in normal and cancer populations. The c-Ha-ras gene is highly polymorphic in Japanese as previously reported in Caucasians. Two rare alleles were found to be present with increased frequencies in Japanese cancer patients. These results suggest that genotype analysis of the c-Ha-ras gene could be used to detect cancer-prone individuals. PMID- 2900799 TI - Psychopharmacologic approaches to the borderline patient. AB - Five case examples are presented to illustrate the role of psychopharmacology in the treatment of patients diagnosed as Borderline Personality Disorders. The cases range from organic through affective and schizophrenic syndromes which are not infrequently at the "border" of personality disorders, and which often respond to specific pharmacologic interventions. The importance of looking for and recognizing drug treatable syndromes within the wide array of patients who satisfy DSM-III criteria for Borderline Disorders is discussed. PMID- 2900801 TI - DNA haplotype distribution in Algerian beta thalassaemia patients. An extended evaluation by family studies and representative molecular characterization. AB - An evaluation of beta thalassaemia mutations and the associated chromosomal haplotypes has been made among Algerian thalassaemic patients in this extended series. The major features of our findings are: (i) due to elevated proportion of consanguinity, the frequency of true homozygotes for a defect is high; (ii) Despite this high homozygosity within families, the number of molecular defects resulting in beta thalassaemia are very heterogeneous within this population. This is exemplified not only by the high heterogeneity of haplotypes and associated mutations, but also by the definition of several new haplotypes, among which two of them were found to be associated with novel mutations. Family studies have been performed in parallel to evaluate the degree of feasibility of antenatal diagnosis in this population. PMID- 2900802 TI - Origin of the extra chromosome in trisomy 18. A study on five patients using a restriction fragment length polymorphism. AB - The parental origin of an extra chromosome in five patients with trisomy 18 was traced using a restriction fragment length polymorphism (RFLP) of the human prealbumin (PA) gene, localized to 18p11.1-q12.1, as a genetic marker. MspI digests of the genomic DNAs of the five patients, their parents and normal controls were hybridized with the PA-cDNA. Densitometric analysis on the gene dose of the polymorphic fragments of these patients revealed that three had originated from a maternal meiotic error. The other two patients were uninformative for the parental origin of trisomy 18. Our results indicate that nondisjunctional errors leading to trisomy 18 may occur predominantly at the maternal meiosis, consistent with the results of previous studies on the parental origin of trisomies 21 and 13. PMID- 2900803 TI - DNA polymorphisms within the porphobilinogen deaminase gene in two Swedish families with acute intermittent porphyria. AB - Two unrelated families with acute intermittent porphyria (AIP), an autosomal dominant disease related to a defect in porphobilinogen deaminase (PBG-D, EC 4.1.3.8.), were studied with regard to three restriction fragment length polymorphisms (RFLPs) (MspI, PstI, BstNI) within the PBG-D gene. The results indicate that linkage analysis of RFLPs within the gene can be used as a complement to PBG-D analysis for the diagnosis of gene carriers in families with AIP. PMID- 2900805 TI - A deletion hot spot in the Duchenne muscular dystrophy gene. AB - We have made a detailed study of a deletion hot spot in the distal half of the Duchenne muscular dystrophy (DMD) gene, using intragenic probe P20 (DXS269), isolated by a hybrid cell-mediated cloning procedure. P20 detects 16% deletions in patients suffering from either DMD or Becker muscular dystrophy (BMD), in sharp contrast to the adjacent intragenic markers JBir (7%) and J66 (less than 1%), mapping respectively 200-320 kb proximal and 380-500 kb distal to P20. Of the P20 deletions, 30% start within a region of 25-40 kb, the majority extending distally. P20 was confirmed to map internal to a distal intron of the DMD gene. This region was recently shown by both cDNA analysis (M. Koenig et al., 1987; Cell 50: 509-517), and field inversion electrophoresis studies (J.T. Den Dunnen et al., 1987, Nature (London) 329: 640-642) to be specifically prone to deletions. In addition, P20 detects MspI and EcoRV RFLPs, informative in 48% of the carrier females. Together, these properties make P20 useful for carrier detection, prenatal diagnosis, and the study of deletion induction in both DMD and BMD. PMID- 2900804 TI - Linkage relationship between retinoschisis and four marker loci. AB - The linkage relationship between the locus for juvenile retinoschisis (RS) and four X-chromosomal marker loci DXS9 (RC8), DXS16 (XUT23), DXS41 (99-6), and DXS43 (D2) has been studied in six families showing a history of this disease. Recombination with RS was found for all marker loci except DXS9. The maximum lod score is zeta = 2.66 for RS vs. DXS9 at a recombination fraction of theta = 0.0. Multipoint linkage analysis was performed and the locus order best supported by our data is: RS - DXS9 - DXS43 - DXS16 - DXS41. PMID- 2900806 TI - Linkage analysis of the properdin deficiency gene: suggestion of a locus in the proximal part of the short arm of the X chromosome. AB - Properdin is a component of the alternative pathway of complement activation. Inherited deficiency of the protein predisposes an individual to develop meningococcal disease. A family segregating for properdin deficiency (McKNo 31206), in a manner consistent with X-linked recessive inheritance, was studied by RFLP analysis using 24 X-chromosome-specific DNA probes of known regional assignments. Linkage was observed to the OTC locus and the DXS7 locus. These results suggest that the properdin gene is located on the short arm of the X chromosome in the region Xp21.1-Xcen. PMID- 2900807 TI - Restriction fragment length polymorphism analysis and assignment of the metalloproteinases stromelysin and collagenase to the long arm of chromosome 11. AB - Collagenase and stromelysin are two metalloproteinases produced mainly by connective tissue cells and involved in the breakdown of the extracellular matrix. cDNA clones for both of these genes have been isolated and sequencing has shown them to be closely related. The collagenase and stromeylsin cDNA clones have been used to assign these genes to the long arm of chromosome 11 in the regions 11q21-22.1 and 11q22.2-22.3, respectively. This has been achieved using somatic cell hybrids and in situ hybridization. In addition a Taq1 restriction fragment length polymorphism has been demonstrated using the stromelysin cDNA. PMID- 2900808 TI - Fine mapping of gene probes and anonymous DNA fragments to the long arm of chromosome 16. AB - The fragile site, FRA16B, at 16q22.100 and four different translocations with breakpoints at 16q22.102, 16q22.105, 16q22.108, and 16q22.3 were used to locate and order DNA probes. This was achieved by Southern analysis of a somatic cell hybrid panel containing portions of chromosome 16 and by in situ hybridization. The anonymous DNA fragments D16S6, D16S10, and D16S11 were proximal to FRA16B and located at 16q13----q22.100. D16S4 and LCAT were located at 16q22.100----q22.102. TAT and HP were located at 16q22.105----q22.108. CTRB was located distal to 16q22.105 and therefore is in the distal half of 16q22. The order of markers in this region was determined as centromere-D16S6, D16S11, D16S10, MT-FRA16B-D16S4, LCAT-HP,TAT,CTRB-APRT- telomere. Linkage studies to determine map distances between the closest markers flanking the fragile site are now in progress. PMID- 2900809 TI - A primary genetic map of markers of human chromosome 10. AB - We have constructed a primary genetic map for human chromosome 10 from 13 polymorphic marker systems defining 11 loci, using a new gene mapping algorithm implemented in the computer program GMS. The loci form a continuous genetic map that spans approximately 116 cM in males and 170 cM in females. These loci provide regularly spaced anchor points for linkage studies, except for one interval that is 28 cM in males and 64 cM in females. PMID- 2900810 TI - Polymorphic Bgl II restriction sites of DR alpha demarcate a novel HLA-DR1 antigen. AB - Mechanisms to account for the unusual properties of a DR1 alpha beta complex (designated DRgp50) that is resistant to dissociation under normal conditions utilized were investigated. Expression of this DRgp50 complex is highly correlated with the failure of cells from certain DR1 individuals (DR1x) to stimulate specific DR1-restricted or alloreactive T-cell clones. Pulse/chase experiments demonstrated that this DRgp50 complex was not detectable until approximately 1 h of chase. The DR1 alpha and beta chains associated into the heterodimer in the absence of glycosylation and alterations in the number of oligosaccharides or sialylation of cell surface forms were not evident when compared with normal DR1 alpha and beta chains. Restriction fragment length polymorphism patterns of DR beta genes from normal (DR1n) and DR1x individuals were indistinguishable. However, a difference in the alpha chain genes between DR1n and DR1x individuals was revealed using Bgl II. This Bgl II restriction site mapped to the 3' untranslated region of DR alpha and represents a new genomic marker to distinguish this functional and biochemical variant of DR1. PMID- 2900811 TI - First domain encoding sequence mediates human class II beta-chain gene cross hybridization. AB - HLA class II molecules are surface heterodimers which are essential in the initiation of immune responses. The amount of polymorphism expressed by the different class II molecules is largely dependent on the polymorphic structure of their beta chains. Cross-hybridization between class II beta genes frequently hampered restriction fragment length polymorphism analysis of donor genomic DNA. In this report we show that the cross-hybridization between human class II beta genes is mediated by a region of high homology, rich in C and G residues, between the first domain encoding sequences of DP, DQ, and DR genes. The removal of the DNA segment containing this region from the fragments used as labeled probes against the corresponding fragments of the genes at other loci or against endonuclease digested genomic DNA completely eliminated or drastically reduced the cross-hybridization. Also, the RFLP patterns generated with the shortened probes were more informative and much simpler to interpret than were these generated with probes made from the original genes. PMID- 2900812 TI - Expression of K99 adhesion antigen controlled by the Escherichia coli tryptophan operon promoter. AB - The genetic determinant for the K99 adhesin of enterotoxigenic Escherichia coli B41 [O101:K99] has been cloned as a 7.0-kilobase BamHI-generated DNA fragment into the vector pBR322 by us and others (J. D. A. van Embden, F. K. de Graaf, L. M. Schouls, and J. S. Teppma, Infect. Immun. 29:1125-1133, 1980). Cells harboring one such construction, known as pK99-64, are capable of expressing K99 antigen on the cell surface. We replaced the natural promoter sequence for the gene encoding the K99 pilus subunit with a strong, inducible exogenous promoter, the E. coli tryptophan (trp) operon promoter, to construct the plasmid pBR-TrpK99. E. coli cells harboring pBR-TrpK99 or a similar construction in the plasmid pDR540, known as pKO-TrpK99, upon induction with 3-beta-indoleacrylic acid, produced about fourfold more K99 antigen than did cells bearing pK99-64 with the natural promoter. Expression of the pilus antigen was found to be under control of the tryptophan promoter. Plasmid instability was encountered, however, in cells bearing pKO-TrpK99 when the trp promoter was derepressed. Introduction of the aminoglycoside 3'-phosphotransferase gene of transposable element Tn5 into pKO TrpK99 to generate pKON-TrpK99 effectively stabilized the plasmid in cells grown under identical conditions in medium containing kanamycin. PMID- 2900813 TI - Detection of pilus subunits (pilins) and filaments by using anti-P pilin antisera. AB - P pilus filaments are important in binding to globoside through an adhesin located at the tip of the pilus. There is considerable antigenic variation among P pili, and the immunologic response is usually serotype specific. We purified denatured pilin subunits and used them as immunogens to prepare more broadly cross-reactive antisera. Although antifilament antisera (AFA) detected predominantly the homologous strain, antisubunit antisera (ASA) prepared from two different strains detected P pili in 16 of 16 and 14 of 16 P-piliated strains by Western blotting (immunoblotting). The binding of ASA to the homologous pilus filament was inhibited by only 3 of 17 strains. ASA agglutinated only two of nine heterologous strains and immunoprecipitated pili from one of three heterologous strains. By immunoelectron microscopy ASA was seen to bind to pilus filaments but not as strongly as AFA. Antiserum raised to the denatured pilin subunit was not substantially more reactive with pilus filaments derived from heterologous strains than was AFA. ASA was, however, a very useful probe for detecting most P pilins. PMID- 2900814 TI - Morphological differences in Neisseria meningitidis pili. AB - Disease and carrier isolates of Neisseria meningitidis were examined for their ability to adhere to human buccal epithelial cells and human cell lines and to hemagglutinate human erythrocytes, properties thought to be associated with the presence of pili. Seventy percent (7 of 10) of carrier isolates were found to be highly adherent to human buccal epithelial cells and to agglutinate human A, B, O, Rh-, and Rh+ erythrocytes. In contrast, 60% of the disease isolates adhered poorly to human buccal epithelial cells and 80% failed to agglutinate human erythrocytes. No adherence of either disease or carrier isolates was observed when several human cell lines were tested. When the meningococcal strains were examined by electron microscopy, 7 of 10 disease isolates were found to possess large bundles of aggregated pili (alpha-type pili), while 7 of 10 carrier isolates were found to have numerous unaggregated pili (beta-type pili). A monoclonal antibody against meningococcal pili and one against gonococcal pili reacted with 6 of 10 piliated carrier isolates and 4 of 10 piliated disease isolates. These results suggest that meningococci, like gonococci, possess different types of pili which differ in morphological, antigenic, and binding properties. In addition, antigenic and morphological differences between pili from carrier and disease isolates were observed as well as differences in adherence and hemagglutinating properties. PMID- 2900815 TI - Effect of unilateral cryptorchidism on the intertubular tissue of the adult rat testis: evidence for intracellular changes within the Leydig cells. AB - Adult male rats were made unilaterally cryptorchid for 1, 2 or 4 weeks, and the morphological response of the Leydig cells was then studied using morphometric assessment of total Leydig cell volume and number per testis in abdominal and scrotal testes. Serum hormone levels were measured and the steroidogenic properties of isolated Leydig cells were evaluated by in-vitro stimulation with hCG and interstitial fluid (IF) obtained from normal rat testes. Total Leydig cell volume and number per testis were not altered in abdominal vs scrotal testes, although the volume of the abdominal testis was 46, 29 and 21%, respectively, of the volume of the contralateral scrotal testis after 1, 2 and 4 weeks. This reduction was accompanied by significant (P less than 0.05) elevation of the serum levels of FSH and LH, although serum testosterone levels were unchanged from the normal range. Despite the lack of quantitative alterations in Leydig cell morphology, hCG- and IF-stimulated testosterone production was significantly (P less than 0.01) greater by abdominal Leydig cells when compared with scrotal Leydig cells derived from the same animals. Ultrastructural examination of Leydig cells in situ suggested an increase in volumetric density of mitochondria in abdominal Leydig cells. Together with the enhanced steroidogenic responses of these cells, these findings suggest that disruption of spermatogenesis in the cryptorchid testis is accompanied by intracellular activation of Leydig cells. Since these effects were not exhibited by Leydig cells from the scrotal testis it is concluded that local factors within the cryptorchid testis are responsible, at least in part, for regulation of Leydig cell activity. PMID- 2900816 TI - A comparison of the bronchodilator effects of broxaterol and salbutamol. AB - In 12 adult patients with reversible bronchospasm (7 bronchial asthma and 5 chronic obstructive bronchitis) the bronchodilator activity and tolerability of 200 and 400 mcg of broxaterol hydrochloride (Z 1170) were compared to those of 200 mcg of salbutamol administered by metered-dose inhaler. A single dose of the drugs was compared in a double-blind balanced latin square cross-over design. FEV1, FVC, MMEF, MEF25, heart rate and blood pressure were measured just before and 7.5, 15, 30, 60, 120, 180 and 240 min after each treatment. At these times clinical evaluation was also carried out to ascertain the presence of side effects. In the doses employed, broxaterol and salbutamol caused significant increases over baseline FEV1, MMEF and MEF25 from 7.5 to 240 min and FVC from 7.5 to 120 min. The difference between the effects of the two doses of broxaterol on FVC, MMEF and MEF25 was significant at 15 min. No significant difference was observed in the activity curves of 400 mcg of broxaterol and salbutamol. The effects of salbutamol were significantly greater than those of 200 mcg of broxaterol on FEV1 at 7.5 and 15 min and on FVC, MMEF and MEF25 at 15 min. All three treatments were well tolerated. No significant changes were observed in heart rate or blood pressure and tremors were not reported in any patient. PMID- 2900817 TI - The effect of food or milk on the bioavailability of etintidine in healthy subjects. AB - A three-way crossover study was conducted in 24 normal, male volunteers to compare the bioavailability of etintidine from capsules (2 X 200 mg) taken under fasting conditions, with food and with milk. Blood samples were collected prior to and at various times after each treatment and plasma levels of etintidine were determined by high performance liquid chromatography. Statistical analysis of the plasma etintidine concentration data indicated that while neither food nor milk had an apparent effect (p greater than 0.05) on the rate of etintidine absorption, both food alone and milk alone slightly decreased the extent of etintidine absorption. Mean bioavailability parameters of etintidine obtained following the administration of etintidine with food, milk or under fasting conditions are 5.28, 5.26 and 5.88 micrograms.h/ml, respectively (for AUC) and 1.75, 2.18 and 2.59 micrograms/ml, respectively (for Cmax), and 1.23, 1.01 and 0.91 h, respectively (for tmax). Symmetrical 95% confidence interval analyses showed that the observed decreases of less than 11% in the AUC values of etintidine following the concomitant administration of food or milk were within 17% of the fasting value and, therefore, may not be of clinical significance. PMID- 2900818 TI - Esmolol: a short-acting titratable beta-blocker in acute myocardial ischemia. AB - Esmolol (Brevibloc) is a potent, titratable, cardioselective beta-blocker with a short elimination half-life (t1/2 = 9.2 min) and no intrinsic sympathomimetic activity. It was designed for use in critically ill patients who would benefit from the short duration of beta-adrenergic blockade. Esmolol's short duration of action allows for rapid onset and control of hemodynamic effects. Its safety and efficacy has been demonstrated in patients with acute myocardial ischemia. This review provides a brief summary of the pharmacology of esmolol, as well as experimental and clinical evidence on the use of esmolol in acute myocardial ischemia. PMID- 2900819 TI - Esmolol attenuates tachycardia caused by tracheal intubation: a double-blind study. AB - A new cardioselective and rapidly metabolized beta-blocker, esmolol (E), was given to prevent post-intubation tachycardia in 40 ASA Class PS I-II patients induced with thiopental, succinylcholine, N2O: O2 and enflurane sequence. The control group (A, n = 10) received 5% D/W. Three study groups received E loading doses of 500 micrograms/kg/min for 1 min (B, n = 8), 2 min (C, n = 10) and 4 min (D, n = 12); the continuous i.v. maintenance doses were 100, 200 and 300 micrograms/kg/min for a total of 10 min, respectively. The pre-esmolol heart rates were 85 +/- 4 in group A, 80 +/- 5 in B, 77 +/- 5 in C, 83 +/- 5 in D; at anesthetic induction and at 4 min after E-infusion, heart rates were 93 +/- 5, 65 +/- 4, 71 +/- 4, 70 +/- 5, respectively; three min post-intubation heart rates were in the control group 111 +/- 4 and 82 +/- 5, 93 +/- 5, 85 +/- 4, respectively, in the E-treated groups. Group A showed marked tachycardia (p less than or equal to 0.001) not observed in the treated groups B, C, D. A significant blockade of HR increases at all infusion rates of E (p less than or equal to 0.05) was found. E at all doses reduced the significant increase in BP observed in Group A. Catecholamine increases were identical and not significantly different among the groups. No adverse effects e.g. bradycardia, arrhythmias and hypotension caused by E or intubation were seen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900820 TI - Peptide conformation. 48. Conformation and biological activity of proline containing cyclic retro-analogues of somatostatin. AB - Six cyclic retro-analogues of the peptide hormone somatostatin have been synthesized using the solid phase technique. The peptides cyclo(-Xaa1-Phe2-Thr3 Lys4-Ybb5-Phe6-) and cyclo(-Phe1-Xaa2-Thr3-Lys4-Ybb5-Phe6-) with Xaa = D- or L Pro and Ybb = D- or L-Trp were cyclized via the azide method. The conformations of the cyclic hexapeptides in DMSO-d6 solution were determined by a number of homo- and heteronuclear two-dimensional n.m.r.-techniques including 2D rotating frame NOE-spectroscopy. Two-step coherence transfers, ROE and chemical exchange, are observed for the first time in ROESY spectra. The backbone conformation of the all-trans cyclopeptides consists of a beta-turn containing the Pro residue in the position i + 1. These retro-analogues of somatostatin exhibit a high activity in the inhibition of cholate and phalloidin uptake by liver cells (cytoprotective effect); however, the hormonal activities of the natural hormone are completely suppressed. The constitutional and conformational requirements for the cytoprotective activity are discussed. PMID- 2900821 TI - Identification of messenger RNA for nucleocapsid protein of Lassa virus in infected cells. AB - Single-stranded RNAs from Lassa virus-infected cells were fractionated by affinity chromatography on an oligo(dT)-cellulose column as well as by sucrose gradient centrifugation. Fractionated RNAs were translated in rabbit reticulocyte lysates, and translation products were precipitated with monoclonal antibodies to the nucleocapsid protein of Lassa virus. It has been shown that mRNA for the nucleocapsid protein is 15-16S and the RNA does not contain long if any poly(A) sequences. PMID- 2900822 TI - HTLV-I and human disease. PMID- 2900823 TI - HTLV-I-associated T-cell leukemia/lymphoma in Israel. AB - Human T-cell lymphotrophic virus Type I (HTLV-I)-associated adult T-cell leukemia/lymphoma (ATL) is a relatively new clinical entity. The disease is endemic in southwestern Japan, the Caribbean basin, the southeastern United States and Africa. We report the identification of this disease in Israel and review previous cases of HTLV-I infection and ATL in this region. The disease was initially indolent and later clinically aggressive, characterized by hypercalcemia, osteolytic bone lesions, leukemic skin and organ infiltration and opportunistic infection. PMID- 2900824 TI - Physiologic effects of alpha 2-adrenergic receptors. PMID- 2900825 TI - Induction and promotion of gamma-glutamyltranspeptidase-positive foci in the rat liver by methylglyoxal. AB - The effect of pre-(initiation) and post-(promotion) administration of methylglyoxal (MG) on the induction of gamma-glutamyltranspeptidase (GGT) positive foci in the liver of F344 male rats was investigated. GGT-positive foci were produced in dose-related amounts by 0.05 and 0.2% MG in drinking water, either when administered to uninitiated rats or when given in the promotion phase. PMID- 2900826 TI - Amplified allele of the human N-myc oncogene in neuroblastomas. AB - The N-myc amplification unit was investigated using two restriction fragment length polymorphisms for SphI and PvuII which we previously found to occur in the 2nd intron and in the 3' region of the human N-myc oncogene, respectively. All the three haplotypes which are dominant in the Japanese population were observed in the amplified DNA after analyses of a total of 22 DNA samples of fresh neuroblastomas with N-myc amplification. We conclude that only one of the alleles was amplified and that either allele could be amplified with respect to both the SphI and PvuII polymorphisms. PMID- 2900827 TI - No correlation between L-myc restriction fragment length polymorphism and malignancy of human colorectal cancers. AB - The correlation of the restriction fragment length polymorphism (RFLP) pattern of L-myc with the progressive state of cancer and metastases to lymph nodes or other organs were examined in 35 cases of human colorectal cancer by chi 2 analysis. No significant correlation was found. PMID- 2900828 TI - Regulation of glucocorticoid receptors and Na-K ATPase activity by hydrocortisone in proximal tubular epithelial cells. AB - The effect of hydrocortisone (HC) in modulating glucocorticoid receptors (GR) and sodium-potassium adenosine triphosphatase (Na-K ATPase) activity was studied in primary cultures of immunoisolated murine proximal tubular epithelial cells (PTEC). Utilizing monoclonal antibody against stage-specific embryonic antigen-1, a homogeneous population of PTEC was obtained in high yield. The cells were cultured to confluence and further treated for 48 h in serum-free growth medium containing no HC (control); 50 nM HC; or 50 nM HC plus 20 nM of the antiglucocorticoid, RU 38486. PTEC treated with 50 nM HC had 56% of GR binding and 160% Na-K ATPase activity as compared to controls (P less than 0.01). GR binding was abolished by incubation in RU 38486 whereas Na-K ATPase fell below control values (P less than 0.05). Brief incubations of HC-treated PTEC with 0.5 mM ouabain resulted in a fall in GR binding without a change in Na-K ATPase activity. These data indicate that in PTEC, HC regulates GR binding and they suggest that stimulation of Na-K ATPase activity is a direct biological response to this receptor-hormone interaction. Thus, primary cultures of immunoaffinity isolated PTEC offer a good model system for investigating the molecular basis underlying the regulation of GR binding and postreceptor events influenced by glucocorticoids. PMID- 2900829 TI - Cloning and nucleotide sequence of a gene for Actinomyces naeslundii WVU45 type 2 fimbriae. AB - A genomic library of Actinomyces naeslundii WVU45 DNA in Escherichia coli was screened for antigen expression with rabbit antibody against A. naeslundii fimbriae. Western blotting (immunoblotting) of one recombinant clone carrying a 13.8-kilobase-pair insert revealed a 59-kilodalton (kDa) immunoreactive protein. A protein of similar electrophoretic mobility was detected from the isolated fimbrial antigen. Expression of the 59-kDa cloned protein in E. coli was directed by a promoter from the insert. The DNA sequence of the subunit gene was determined, and an open reading frame of 1,605 nucleotides was identified which was preceded by a putative ribosome-binding site and followed by two inverted repeats of 14 and 17 nucleotides, respectively. The reading frame encoded a protein of 534 amino acids (calculated molecular weight, 57,074), and the N terminal sequence resembled that of a signal peptide. The presence of a 32-amino acid signal peptide was indicated by amino-terminal sequencing of the fimbriae from A. naeslundii. The sequence, as determined by Edman degradation, was identical to that deduced from the DNA sequence beginning at predicted residue 33 of the latter sequence. Moreover, the amino acid composition of the predicted mature protein was similar to that of the isolated fimbriae from A. naeslundii. Thus, the cloned gene encodes a subunit of A. naeslundii fimbriae. PMID- 2900831 TI - Gene clusters for S fimbrial adhesin (sfa) and F1C fimbriae (foc) of Escherichia coli: comparative aspects of structure and function. AB - Fimbrial adhesins enable bacteria to attach to eucaryotic cells. The genetic determinants for S fimbrial adhesins (sfa) and for F1C ("pseudotype I") fimbriae (foc) were compared. Sfa and F1C represent functionally distinct adhesins in their receptor specificities. Nevertheless, a high degree of homology between both determinants was found on the basis of DNA-DNA hybridizations. Characteristic differences in the restriction maps of the corresponding gene clusters, however, were visible in regions coding for the fimbrial subunits and for the S-specific adhesin. While a plasmid carrying the genetic determinant for F1C fimbriae was able to complement transposon-induced sfa mutants, a plasmid carrying the genetic determinant for a third adhesin type, termed P fimbriae, was unable to do so. Proximal sfa-specific sequences carrying the S fimbrial structural gene were fused to sequences representing the distal part of the foc gene cluster to form a hybrid cluster, and the foc proximal region coding for the structural protein was ligated to sfa distal sequences to form a second hybrid. Both hybrid clones produced intact fimbriae. Anti-F1C monoclonal antibodies (MAbs) only recognized clones which produced F1C fimbriae, and an anti-S adhesin MAb marked clones which expressed the S adhesin. However, one of four other anti S fimbriae-specific MAbs reacted with both fimbrial structures, S and F1C, indicating a common epitope on both antigens. The results presented here support the view that sfa and foc determinants code for fimbriae that are similar in several aspects, while the P fimbriae are members of a more distantly related group. PMID- 2900830 TI - Formation of the chlorophyll precursor delta-aminolevulinic acid in cyanobacteria requires aminoacylation of a tRNAGlu species. AB - In the chloroplasts of higher plants and algae, the biosynthesis of the chlorophyll precursor delta-aminolevulinic acid (ALA) involves at least three enzymes and a tRNA species. Here we demonstrate that in cell extracts of the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 ALA was formed from glutamate in a series of reactions in which activation of glutamate by glutamyl tRNAGlu formation was the first step. The activated glutamate was reduced by a dehydrogenase which displayed tRNA sequence specificity. Fractionation of strain 6803 tRNA by reverse-phase chromatography and polyacrylamide gel electrophoresis yielded two pure tRNAGlu species which stimulated ALA synthesis in vitro. These tRNAs had identical primary sequences but differed in the nucleotide modification of their anticodon. The 6803 tRNAGlu was similar to the sequences of tRNAGlu species or tRNAGlu genes from Escherichia coli and from chloroplasts of Euglena gracilis and higher plants. Southern blot analysis revealed at least two tRNAGlu gene copies in the 6803 chromosome. A glutamate-1-semialdehyde aminotransferase, the terminal enzyme in the conversion of glutamate to ALA in chloroplasts, was detected in 6803 cell extracts by the conversion of glutamate-1-semialdehyde to ALA and by the inhibition of this reaction by gabaculin. PMID- 2900833 TI - The multidrug transporter, a double-edged sword. PMID- 2900832 TI - Cloning and expression of a Salmonella enteritidis fimbrin gene in Escherichia coli. AB - A gene bank of DNA from a human isolate of Salmonella enteritidis was constructed in the cosmid pHC79 in Escherichia coli HB101. Five clones containing 35- to 45 kilobase inserts of S. enteritidis DNA reacted in colony immunoblot assays with a polyclonal antiserum prepared against purified S. enteritidis fimbriae. Electron microscopy showed that none of the five fimbrin-producing clones produced fimbriae, yet radioimmunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis located the 14,400-molecular-weight S. enteritidis in the outer membrane fraction of three of the clones and in the periplasmic fraction of all five clones. By using an oligonucleotide probe homologous to the 5' region of the fimbrin structural gene, the fimbrin gene was located on a 5.3-kilobase HindIII fragment. In vitro transcription-translation analysis verified that this HindIII fragment subcloned into plasmid pTZ18R produced unprocessed S. enteritidis fimbrin of molecular weight 16,400. Dot blot hybridization against a selection of strains of the family Enterobacteriaceae indicated a limited distribution of the S. enteritidis fimbrin gene. PMID- 2900834 TI - Short-term metabolic fate of 13N-labeled glutamate, alanine, and glutamine(amide) in rat liver. AB - Tracer quantities (in 0.2 ml) of 13N-labeled glutamate, alanine, or glutamine(amide) were administered rapidly (less than or equal to 2 s) via the portal vein of anesthetized adult male rats. Liver content of tracer at 5 s was 57 +/- 6 (n = 6), 24 +/- 1 (n = 3), and 69 +/- 7 (n = 3)% of the injected dose, respectively. Portal-hepatic vein differences for the corresponding amino acids were 17 +/- 6, 26 +/- 8, and 19 +/- 9% (n = 4), respectively, suggesting some export of glutamate and glutamine, but not of alanine, to the hepatic vein. Following L-[13N]glutamate administration, label rapidly appeared in liver alanine and aspartate (within seconds). The data emphasize the rapidity of nitrogen exchange via linked transaminases. By 30 s following administration of either L-[13N]glutamate or L-[13N]alanine, label in liver glutamate was comparable; yet, by 1 min greater than or equal to 9 times as much label was present in liver glutamine(amine) following L-[13N]glutamate administration than following L-[13N]alanine administration. Conversely, label in liver urea at 1 min was more pronounced in the latter case despite: (a) comparable total pool sizes of glutamate and alanine in liver; and (b) label incorporation from alanine into urea must occur via prior transfer of alanine nitrogen to glutamate. The data provide evidence for zonal differences in uptake of alanine and glutamate from the portal vein in vivo. The rate of turnover of L-[amide-13N]glutamine was considerably slower than that of L-[13N]alanine or of L-[13N]glutamate, presumably due in part to the higher concentration of glutamine in that organ. Nevertheless, it was possible to show that despite occasional suggestions to the contrary, glutamine(amide) is a source of urea nitrogen in vivo. The present findings continue to emphasize the rapidity of nitrogen exchange reactions in vivo. PMID- 2900835 TI - Primary structure of the multifunctional alpha subunit protein of yeast fatty acid synthase derived from FAS2 gene sequence. AB - The yeast fatty acid synthase consists of two multifunctional proteins, alpha and beta, arranged in an alpha 6 beta 6 complex with a molecular weight of 2.4 x 10(6). Five of the seven enzymatic activities reside in the beta subunit, while the remaining two activities, beta-ketoacyl synthase and beta-ketoacyl reductase, and the domain of the acyl carrier protein, with its prosthetic group, 4' phosphopantetheine, are in the alpha subunit. The genes FAS1 and FAS2 coding for beta and alpha subunits, respectively, have been cloned and the sequence of FAS1 has been reported (Chirala, S. S., Kuziora, M. A., Spector, D. M., and Wakil, S. J. (1987) J. Biol. Chem. 262, 4231-4240). In this study, we present the nucleotide sequence of the FAS2 gene. The sequence has an open reading frame, coding for a protein of 1894 amino acids with a calculated molecular weight of 207,863. The location of the serine site of attachment of the prosthetic group of the acyl carrier protein domain and the active cysteine-SH site of beta-ketoacyl synthase have been identified at residues 180 and 1312, respectively, in the deduced amino acid sequence. A putative NADPH binding site of beta-ketoacyl reductase has been suggested at residue 1038 based on the similarities to the consensus amino acid sequences -Gly-Ser-Ala- of the pyridine nucleotide enzymes. We could not find any sequence homology in the 5' flanking sequence of the FAS1 and FAS2 genes that would suggest common regulatory function. However, in the sequence of these two genes there is an identical eight-base pair sequence TCATTATG at the translational initiation site suggesting that the subunit stoichiometry probably results from equal translational efficiency of the mRNAs of both FAS1 and FAS2 genes. The S1 endonuclease mapping suggests that there is a transcriptional initiation site at about 40 nucleotides upstream of the first ATG codon and a transcriptional termination site about 300 nucleotides downstream of the TAG stop codon. The gene does not contain introns as no intron consensus TACTAAC have been found in the sequence. PMID- 2900836 TI - Phosphorylation of bovine adrenal chromaffin cell tyrosine hydroxylase. Temporal correlation of acetylcholine's effect on site phosphorylation, enzyme activation, and catecholamine synthesis. AB - Tryptic peptide fragments of tyrosine hydroxylase isolated from 32PO4-prelabeled bovine adrenal chromaffin cells are resolved into seven phosphopeptides by reverse phase-high performance liquid chromatography. All seven of the peptides are phosphorylated on serine residues. Three of these putative phosphorylation sites, peptides 3, 5, and 6, are rapidly phosphorylated (5-fold in 15 s) by both acetylcholine stimulation and potassium depolarization of the cells, and this phosphorylation is accompanied by a similarly rapid activation of the enzyme. Both phosphorylation and activation are transient and do not account for the prolonged increase in catecholamine biosynthesis produced by these stimuli. Peptides 4 and 7 show a much slower and sustained increase in phosphorylation (3 fold in 4 min) in response to acetylcholine and potassium. Phosphorylation of these peptides correlates with the sustained increase in catecholamine biosynthesis rather than enzyme activation. Peptides 1 and 2 are not stimulated by any agonist yet employed and thus show no relation to enzyme activation or catecholamine biosynthesis. Phosphorylation of all five peptides by acetylcholine or potassium is calcium-dependent. In contrast to the stimulation of phosphorylation of tyrosine hydroxylase on multiple sites, forskolin stimulates the phosphorylation of only peptide 6, and this is accompanied by a coordinated activation of tyrosine hydroxylase and increased catecholamine biosynthesis. These findings show that the phosphorylation of tyrosine hydroxylase in intact cells is more complex than predicted from in vitro results, that at least two protein kinases are involved in the secretagogue-induced phosphorylation of tyrosine hydroxylase, and that the regulation of catecholamine biosynthesis, in response to phosphorylation, appears to involve both tyrosine hydroxylase activation and other mechanisms. PMID- 2900837 TI - Beta-adrenergic receptor stimulation induces inositol trisphosphate production and Ca2+ mobilization in rat parotid acinar cells. AB - In dispersed rat parotid gland acinar cells, the beta-adrenergic agonist (-) isoproterenol, but not its stereoisomer (+)-isoproterenol, induced a transient 1.6-fold (at maximum stimulation, 2 x 10(-4) M) increase in cytosolic free calcium ([Ca2+]i) within 9 s, which returned to resting levels (approximately 190 nM) by 60 s. This [Ca2+]i response was not altered by chelating extracellular Ca2+ with [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) and could be completely blocked by the beta-adrenergic antagonists propranolol (beta 1 + beta 2) and ICI 118,551 (beta 2) but not by atenolol (beta 1). The muscarinic cholinergic agonist carbachol (at maximum stimulation, 10(-5) M) induced a 3-4 fold elevation in [Ca2+]i within 6 s, which slowly returned to resting levels by 8-10 min. The peak carbachol [Ca2+]i response was not substantially altered by the addition of EGTA to the extracellular medium. However, if the cells were first stimulated with isoproterenol in the EGTA-containing medium, the peak carbachol response was decreased approximately 54%. When carbachol was added to cells in the presence of high extracellular calcium, at the isoproterenol stimulated [Ca2+]i peak, the resulting [Ca2+]i level was equal to that achieved when carbachol was either added alone or added after propranolol and isoproterenol. 8-Bromo-cyclic AMP induced a [Ca2+]i response similar to that elicited by isoproterenol, which was not additive to that by carbachol. Carbachol induced a approximately 3.5-fold increase in inositol trisphosphate (IP3) production in parotid cells within 30 s. 8-Bromo-cAMP, N6,O2'-dioctanoyl-cAMP, and isoproterenol consistently induced a significant stimulation in IP3 production. The half-maximal concentration of isoproterenol required for [Ca2+]i mobilization and IP3 production was comparable (approximately 10(-5) M). Isoproterenol-induced IP3 formation was blocked by propranolol. The data show that in rat parotid acinar cells, beta-adrenergic stimulation results in IP3 formation and mobilization of a carbachol-sensitive intracellular Ca2+ pool by a mechanism involving cAMP. This demonstrates an interaction between the cAMP and phosphoinositide second messenger systems in these cells. PMID- 2900838 TI - Characterization of a hydrophilic form of Thy-1 purified from human cerebrospinal fluid. AB - Thy-1 is a developmentally regulated cell surface glycoprotein in nervous tissue. An inositol-containing glycolipid structure is covalently attached to its carboxyl terminus, which anchors the protein to the cell membrane. In the present paper we report the characterization of a water-soluble form of Thy-1, purified from human cerebrospinal fluid (CSF). In contrast to the membrane-bound form of Thy-1 (M-Thy-1) isolated from human brain cerebral cortex, CSF-Thy-1 behaved like a completely hydrophilic glycoprotein, as analyzed by charge-shift electrophoresis in the presence of detergents and by liposome incorporation experiments. CSF-Thy-1 displayed a slightly higher apparent molecular weight in sodium dodecyl sulfate-polyacrylamide gel electrophoresis than M-Thy-1. Digestions with endoglycosidases demonstrated that this difference in size was correlated to different processing of the three N-linked oligosaccharides, and the mobilities of the deglycosylated molecules were indistinguishable in sodium dodecyl sulfate gels. A Pronase-resistant carboxyl-terminal fragment was isolated from the CSF-Thy-1 after trypsin digestion and compared with the corresponding structure of M-Thy-1, obtained by treatment either with bacterial phosphatidylinositol-specific phospholipase C or with human serum (as a source of phosphatidylinositol-specific phospholipase D). The major fragment from CSF-Thy-1 behaved identically, with respect to size and charge, to the carboxyl-terminal fragment from M-Thy-1 solubilized by phospholipase D. These findings suggest an in vivo release of phosphatidylinositol-anchored Thy-1 glycoprotein from brain cells by the action of an endogenous phospholipase D. PMID- 2900840 TI - Quantitation of pancuronium, 3-desacetylpancuronium, vecuronium, 3 desacetylvecuronium, pipecuronium and 3-desacetylpipecuronium in biological fluids by capillary gas chromatography using nitrogen-sensitive detection. AB - A sensitive and specific capillary gas chromatographic (GC) assay was developed for the quantitation of the quaternary ammonium steroidal neuromuscular blocking drugs pancuronium (PANC), vecuronium (VEC) and pipecuronium (PIP), as well as the metabolites 3-desacetylpancuronium (3-desPANC) and 3-desacetylvecuronium (3-des VEC) in plasma, bile and urine; the putative metabolite 3-desacetylpipecuronium (3-des PIP) was extracted and quantitated only in urine. The procedure employed a single dichloromethane extraction of the iodide ion-pairs of the monoquaternary or bisquaternary ammonium compounds (including internal and external standards) from acidified, ether-washed biological fluid followed by the formation of stable O-tert.-butyldimethylsilyl derivatives at the 3-hydroxy steroidal position of the metabolites. An automated capillary GC system fitted with a nitrogen-sensitive detector and an integrator was then used to analyze and quantitate both parent compounds and their derivatized metabolites. Optimal extraction, derivatization and GC conditions, as well as short-term stability and recoveries of these drugs and metabolites in plasma, are reported. Electron ionization mass spectrometry combined with GC was used to confirm the identities of compounds eluted from the column. The assay demonstrated a 10(3)-fold linear range up to 5000 ng/ml for PANC, VEC, 3-des VEC and PIP, and lower limits of detection with adequate precision of 2 ng/ml for PANC, VEC and PIP, and 4 ng/ml for 3-des VEC; 3-des PANC was linear from 8 to 500 ng/ml while 3-des PIP was linear from 25 to 1000 ng/ml. The precision (coefficient of variation) of the calibration curves for underivatized drugs and their derivatized metabolites over the linear ranges was 2-20% and the reproducibility of the assay over a range of clinical concentrations of these drugs found in human plasma was 5-16% for PANC, 2-4% for VEC and 6-11% for PIP. No interferences were detected in the assay of plasma samples from 106 surgical patients. PMID- 2900841 TI - Simple assay procedure for tyrosine hydroxylase activity by high-performance liquid chromatography employing coulometric detection with minimal sample preparation. AB - A simple assay procedure for tyrosine hydroxylase activity in crude tissue samples was devised that requires minimal sample preparation and use of high performance liquid chromatography with coulometric electrochemical detection. After incubation of enzyme samples, such as human brain homogenates or rat pheochromocytoma PC12h cells, with L-tyrosine and a tetrahydropterin cofactor, in the presence or absence of p-bromobenzyloxyamine, an inhibitor of aromatic L amino acid decarboxylase, the reaction was terminated by addition of an equal volume of 0.1 M perchloric acid. For quantitation of L-DOPA produced, the sample was centrifuged, filtered and directly applied to the chromatographic apparatus connected to a coulometric electrochemical detector. This method makes redundant a time-consuming step in the previous methods, purification and concentration of L-DOPA or dopamine using alumina. The reaction conditions for the assay of tyrosine hydroxylase activity in brain homogenates and PC12h cells were re examined by this method. Both tyrosine hydroxylase samples required a naturally occurring cofactor, (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin [(6R)BH4], catalase and NSD-1055 for the full activity, and tyrosine hydroxylase in human brain homogenates required Fe2+ ions for its full activity. (6R)BH4 proved to be a more effective cofactor than a synthetic cofactor, (6RS)-methyl-5,6,7,8 tetrahydropterin, which is commonly used for this assay. PMID- 2900839 TI - Time-dependence and differential induction of rat and guinea pig peroxisomal beta oxidation, palmitoyl-CoA hydrolase, cytosolic and microsomal epoxide hydrolase after treatment with hypolipidemic drugs. AB - Fischer-344 rats and Hartley guinea pigs received a diet containing 0.01% (w/w), 0.05% (w/w), or 0.25% (w/w) of the hypolipidemic drug fenofibrate. Rats were treated for 4, 7, 14, or 21 days, and a clear dose-dependent and weak time dependent increase in liver/body weight ratio was observed. The specific activity of peroxisomal beta-oxidation increased linearly with time at all concentrations used. A dose-dependent increase in cEH was observed, but the activity remained constant after treatment for 7 days. Enhancement of palmitoyl-CoA hydrolase was dose-dependent, but was similar at all 4 time points investigated. In contrast to the other enzyme activities, mEH was not or only minimally (less than 1.5-fold) induced. In contrast to the rat, treatment of guinea pigs with fenofibrate for 1 week did not change liver weight or enzyme activities. Prolonged treatment of guinea pigs (4 weeks) with fenofibrate did not result in an increase in enzyme activities. This was also observed with clofibrate whereas tiadenol caused a slight increase in enzyme activities (1.5- to 2.6-fold). In contrast to the guinea pig each of the three hypolipidemic drugs led to an increase in enzyme activities in the rat liver after treatment for 1 week. PMID- 2900842 TI - Effective high-performance liquid chromatographic determination of glafenine in plasma: pharmacokinetic application. AB - A high-performance liquid chromatographic method for an effective determination of glafenine and its main metabolite, glafenic acid, is described. The assay involves separate extraction procedures for glafenine and for its metabolite, but the same internal standard (floctafenine) and the same chromatographic conditions (including a 5-micron C8 column, a quaternary solvent mixture of water acetonitrile-diethylamine-acetic acid and an ultraviolet detector set at 360 nm). For 1 ml of plasma, the detection limit is 0.05 mg/l for glafenine and 0.25 mg/l for glafenic acid. Compared with previously described techniques, this assay uses a very low glafenine linearity range, which allows the true pharmacokinetics of this drug to be described for the first time. PMID- 2900843 TI - A persistent pattern of varying pituitary responsivity to exogenous growth hormone (GH)-releasing hormone in GH-deficient children: evidence supporting periodic somatostatin secretion. AB - The pattern and degree of variation in pituitary responsivity to GHRH was examined in four GH-deficient children (two boys and two girls, aged 4 3/12 to 10 4/12 yr). All children were studied before and on multiple (three to six per child) occasions during long term GHRH therapy (1 or 2 micrograms/kg, sc, every 3 h) in an identical fashion. Each study comprised withdrawal of blood for serum GH measurements every 20 min between 2000 and 0800 h. All subjects received GHRH at 2000, 2300, 0200, and 0500 h as well as at 0800, 1100, 1400, and 1700 h throughout the long term treatment period (6-18 months). Although all children had low level (less than 7.0 micrograms/L) pulsatile GH secretion during baseline studies, the maximal peak values occurred at times other than 0500 h. Before GHRH treatment, serum GH levels rose significantly in response to 91% (62 of 68) of the GHRH doses administered. GH pulse amplitudes varied throughout the studies in all children, and this variability persisted despite 1300-3600 consecutive doses in each child. In all 17 study periods the highest serum GH concentration occurred shortly after the 0500 h GHRH dose. The mean peak GH concentration after the 0500 h GHRH dose [18.4 +/- 3.5 (+/- SE) micrograms/L] was significantly higher than those after the 2000 h (5.3 +/- 1.0 micrograms/L; P = 0.0001), 2300 h (7.4 +/- 2.1 micrograms/L; P = 0.0003), and 0200 h (10.9 +/- 2.5 micrograms/L; P = 0.011) doses. These results demonstrate that the responsivity of the pituitary to GHRH varies throughout the night in some GH-deficient children. There appears to be a direct relationship between the time of night and the degree of pituitary responsivity to GHRH. We suggest that this variable responsivity may be due to intermittent hypothalamic somatostatin secretion. PMID- 2900845 TI - New, practical approach to detecting antibody to pertussis toxin for public health and clinical laboratories. AB - A new, practical method for determining antibody to pertussis toxin (PT) by enzyme-linked immunosorbent assay for public health and clinical laboratories is possible because of recent advances in understanding the pathobiology of Bordetella pertussis and the physicochemical properties of PT. The new approach does not require the use of highly purified PT antigen, which is difficult and expensive for most laboratories to obtain. Moreover, it employs only reagents that are commercially readily available. The method combines the purification of PT antigen and an assay for PT antibody into one process. It depends on (i) growth of B. pertussis in a simple, defined medium to obtain a PT-rich supernatant with little contamination of cellular antigens; (ii) a simple, one step concentration of PT in the culture supernatant with Affi-Gel Blue (Bio-Rad Laboratories, Richmond, Calif.); and (iii) specific adsorption of PT as the test antigen to microtiter wells coated with fetuin for the enzyme-linked immunosorbent assay. The procedure is sensitive and specific for PT antibody. It is technically simple, reproducible, and can be performed in a modestly equipped laboratory. PMID- 2900844 TI - Entamoeba histolytica antigen-specific induction of human immunodeficiency virus replication. AB - Replication of human immunodeficiency virus (HIV) may be initiated in infected lymphocytes by antigenic or mitogenic stimulation. A soluble protein derived from an invasive strain of Entamoeba histolytica (amoebic antigen [AA]) was used to study the lymphoblastic responses of T lymphocytes derived from 8 HIV seronegative homosexual men (controls) and 15 HIV-seropositive homosexual men (patients). The soluble protein was also used in long-term cultures as a stimulus for HIV replication. No control or patient produced detectable lymphoblastic responses to AA in a 6-day tritiated-thymidine incorporation assay. Of 15 patients, 5 (33%) produced HIV p24 (ranging from 31 pg/ml to 151 ng/ml) in response to AA in 30-day cell cultures. HIV p24 was expressed in three of seven patients in response to AA but not to the T-lymphocyte mitogen phytohemagglutinin. Implications for managing HIV-infected patients are discussed. PMID- 2900848 TI - Net portal-drained visceral and hepatic metabolism of glucose, L-lactate, and nitrogenous compounds in lactating holstein cows. AB - Net portal-drained visceral and hepatic flux of glucose, L-lactate, alpha-amino N, NH3N, urea N, glutamate, and glutamine were measured in four Holstein cows. Cows were fed a 60:40 corn silage: concentrate diet ad libitum and milked at 12-h intervals. Six to 16 d postpartum chronic catheters were established in hepatic portal, hepatic, and mesenteric veins and a carotid artery was elevated. Twelve Measurements of net flux, the mathematical product of blood flow (measured by p aminohippurate dilution) and venous-arterial concentration difference, were obtained for each cow at hourly intervals during 1 d of wk 4 and 8 postpartum. Dry matter, N, and energy digestion trials began 1 to 2 d after blood sampling. Dry matter intake and milk yield averaged 15.6 and 32.2 kg/d. Portal-drained visceral blood flow averaged 80% of hepatic blood flow (2041 L/h). Net flux of NH3N, urea N, and alpha-amino N across portal-drained viscera represented 68, 54, and 51% of N apparently digested. There was net use of glucose by portal-drained viscera. Hepatic glucose production (3.1 kg/d) exceeded calculated mammary glucose requirements. Net hepatic removal of L-lactate, alpha-amino N, and NH3N represented 115, 43, and 101%, respectively, of their net absorption by portal drained viscera. Net hepatic L-lactate and alpha-amino N removal could account maximally for 17.4 and 16.5% of glucose produced. PMID- 2900847 TI - Cutaneous Crohn's disease and progressive vitiligo. AB - A patient with Crohn's colitis rapidly developed violaceous papules and plaques on the thigh, breast, and back during an exacerbation of colitis. Biopsy specimens of lesional bowel and skin showed noncaseating granulomatous inflammation consistent with Crohn's disease. The rare occurrence of granulomatous skin lesions widely separated from the perirectal area, previously reported as metastatic Crohn's disease, is reviewed, and the additional finding of concomitant vitiligo with a possible linked pathogenesis is briefly discussed. PMID- 2900846 TI - Immunoblot analysis of humoral immune responses following infection with Bordetella pertussis or immunization with diphtheria-tetanus-pertussis vaccine. AB - To help develop better diagnostic tests for pertussis, we examined the serologic response to whole-cell proteins of Bordetella pertussis after natural infection or vaccination with diphtheria-tetanus-pertussis vaccine. Serum specimens collected during a pertussis outbreak investigation and from uninfected persons were used in Western blot (immunoblot) analyses to determine the presence of immunoglobulin G (IgG) and IgA antibodies to specific B. pertussis proteins. IgG antibodies to proteins of molecular masses 220 and 210 kilodaltons (kDa) were detected in 14 of 18 serum samples obtained from patients with culture-confirmed pertussis greater than or equal to 40 days after the onset of coughing. IgA antibodies were detected in 15 of the 18 samples. Of 19 serum samples obtained from patients who had not been ill with pertussis, 6 contained IgG antibodies to these proteins and 1 contained IgA antibodies. The two proteins bound antiserum specific for filamentous hemagglutinin and comigrated with purified filamentous hemagglutinin. IgG antibodies to two additional protein bands of molecular masses 84 and 75 kDa were associated with previous vaccination. Antibody to the 84-kDa protein was detected in 15 of 17 vaccinated, never-infected persons, and antibody to the 75-kDa protein was detected in 16 of the 17. None of 11 nonvaccinated, never-infected persons tested had antibodies to either protein. All seven fully vaccinated persons with culture-documented infection had antibodies to both proteins. Antibodies to the 84-kDa protein were detected in 6 of 22 nonvaccinated and infected persons, and antibodies to the 75-kDa protein were detected in 8 of the 22. Use of Western blot analysis in this study allowed us to distinguish antibody responses to infection and immunization. PMID- 2900849 TI - Scope and significance of eating disorders. PMID- 2900850 TI - Biological aspects of anorexia nervosa and bulimia nervosa. PMID- 2900851 TI - Measurement of TSAb directly in serum using FRTL-5 cells. AB - FRTL-5 cells were shown to be suitable for the measurement of thyroid stimulating antibody (TSAb) present in sera of patients with Graves' disease. Current methods for the assay of TSAb require the separation of immunoglobulin G (IgG) from patient sera. In this report the possibility to measure TSAb directly on serum was evaluated using FRTL-5 cells. To this purpose cells were seeded in 96-well plates and cultured for 4 days in medium deprived of TSH. Using this system bovine TSH was able to produce a significant stimulation of cAMP production at 1 microU/ml. Whole normal serum completely inhibited the stimulation of TSH as well as that of TSAb, while diluted serum was devoid of any effect. Heat inactivated sera and IgGs, prepared by DEAE Sephadex separation, were diluted in hypotonic medium and incubated with cells for 1 h at 37 C. After incubation cAMP was measured in the assay medium by RIA. In some experiments the effects of graded dilutions of sera and IgGs with known TSAb activity were compared. Sera as well as IgGs increased the cAMP production, but, at the highest concentrations, an inhibitory effect was evident. For this reason sera were tested after appropriate dilution. Thirteen/27 (48%) sera and 22/27 (81%) IgGs from patients with Graves' disease were TSAb positive. The effect of Graves' sera on adenylate cyclase stimulation was completely inhibited by an anti-human IgG. The results of stimulation produced by Graves' sera and IgGs were highly correlated (r = 0.97, p less than 0.001). In conclusion it is possible to measure TSAb directly in serum using FRTL-5 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2900852 TI - On the in vitro neutralization test of Clostridium perfringens type A toxin. AB - Data are presented on the detection in crude animal and human sera of Cl. perfringens phospholipase C (PLC) inhibitor. When the level of Cl. perfringens type A antitoxin is determined in the in vitro toxin neutralization test the inhibitor is found to decrease PLC activity in the test dose of experimental homologous toxin. The extent of decrease accounts for the variation of results obtained in the in vitro and in vivo toxin neutralization tests. The variation may be cancelled out by introducing a corresponding coefficient to calculate the level of alpha-antitoxin. It is suggested that the isolation and investigation of the PLC inhibitor will contribute to the development of preparations for treatment of gas gangrene due to Cl. perfringens type A. PMID- 2900853 TI - The association of DNA variants at or near the IgH locus with rheumatoid arthritis. AB - DNA samples from 78 patients with classical or definite rheumatoid arthritis (RA) and 132 healthy controls were analysed by the Southern blotting method, using two DNA probes: the first to the immunoglobulin mu heavy-chain switch region (S mu), in conjunction with the SstI restriction endonuclease, and the second to the D14S1 region, in conjunction with the HindIII restriction endonuclease. The homozygous phenotype for the 6.9 kb S mu fragment was decreased in the patient group (7.8%) compared to controls (19.1%) (P = 0.04). The homozygous phenotype for the 10.3 kb D14S1 fragment was increased in the patient group (38.5%) compared to controls (21.2%) (P = 0.02). The increase was more pronounced in the DR4-positive patients (51.2%) (P versus DR4-positive controls = 0.009). These results suggest that genes on chromosome 14 are involved in the genetics of RA. PMID- 2900854 TI - IgA2 allotypes determined by restriction fragment length polymorphism in IgA deficiency. Re-expression of the silent A2m(2) allotype in the children of IgA deficient patients. AB - IgA2 allotyping was performed on DNA from 60 IgA-deficient Caucasian individuals. The frequency of A2m(2) was not statistically different from that of normal controls. Two informative families were selected for further studies. In both families, the A2m(2) allotype (derived from the IgA-deficient parent) was inherited by some of the children, as determined by Southern blotting experiments. In all cases the 'silent' IgA2m2 gene was re-expressed, as judged by conventional serological allotyping of serum proteins. These data strongly argue against structural gene deletions or mutations as a cause of IgA deficiency. PMID- 2900855 TI - Heterogeneity and linkage of equine C4 and steroid 21-hydroxylase genes. AB - The fourth component of complement (C4) is polymorphic in most species studied, and is encoded by a gene or genes within the MHC. In man and mouse there are two closely linked C4 and steroid 21-hydroxylase (21-OH) genes. Therefore we have used Southern blotting to determine whether equine C4 and 21-OH genes are linked. C4 restriction fragment length polymorphism (RFLP) was found with the enzymes EcoRI and BamHI. Comparison of the sizes of EcoRI-digested fragments of genomic DNA hybridizing with C4 and 21-OH probes revealed that equine C4 and 21-OH genes are separated by no more than 13 kb. Further, there is no evidence of C4 and 21 OH gene duplication in the horse. Segregation of ELA and different polymorphic forms of equine C4 suggest that C4 and 21-OH genes are within the MHC. It is likely that equine MHC supratypes will provide improved markers of disease susceptibility. PMID- 2900856 TI - Seroepidemiology of human T lymphotropic viruses and hepatitis viruses among prostitutes in Taiwan. PMID- 2900857 TI - [Epidemiology of adult T-cell leukemia in Ehime Prefecture]. PMID- 2900858 TI - The molecular genetics of the incision step in the DNA excision repair process. AB - This review describes the evolution of research into the genetic basis of how different organisms use the process of excision repair to recognize and remove lesions from their cellular DNA. One particular aspect of excision repair, DNA incision, and how it is controlled at the genetic level in bacteriophage, bacteria, S. cerevisae, D. melanogaster, rodent cells and humans is examined. In phage T4, DNA is incised by a DNA glycosylase-AP endonuclease that is coded for by the denV gene. In E. coli, the products of three genes, uvrA, uvrB and uvrC, are required to form the UVRABC excinuclease that cleaves DNA and releases a fragment 12-13 nucleotides long containing the site of damage. In S. cerevisiae, genes complementing five mutants of the RAD3 epistasis group, rad1, rad2, rad3, rad4 and rad10 have been cloned and analyzed. Rodent cells sensitive to a variety of mutagenic agents and deficient in excision repair are being used in molecular studies to identify and clone human repair genes (e.g. ERCC1) capable of complementing mammalian repair defects. Most studies of the human system, however, have been done with cells isolated from patients suffering from the repair defective, cancer-prone disorder, xeroderma pigmentosum, and these cells are now beginning to be characterized at the molecular level. Studies such as these that provide a greater understanding of the genetic basis of DNA repair should also offer new insights into other cellular processes, including genetic recombination, differentiation, mutagenesis, carcinogenesis and aging. PMID- 2900859 TI - Radiation-induced mating-type switching in the yeast Saccharomyces cerevisiae. AB - Haploid yeast cells possess two different mating types which are controlled genetically by the MAT locus. Information of the opposite mating type is stored on the same chromosome but not expressed. Radiation may initiate a gene conversion event leading to 'mating-type switching'. This was studied by using X rays and 254 nm ultraviolet light. X-ray-induced mating type switching shows an oxygen enhancement ratio of 2.9 which is higher than that for survival (1.8) and equals that for double-strand break induction. Mating-type switching by UV is not photoreactivable and depends on a functioning excision repair system. The results are compatible with the interpretation that mating type switching is initiated by a double-strand break in the MAT coding region. PMID- 2900860 TI - Analysis of structural and numerical chromosomal anomalies at the first, second, and third mitosis after irradiation of one-cell mouse embryos with X-rays or neutrons. AB - One-cell mouse embryos were irradiated with X-rays or neutrons. Analysis of the first, second, and third postradiation mitoses revealed that the yields of structural aberrations increased linearly after exposure to both radiation qualities. For X-rays the aberration frequency decreased from the first to the third mitosis, whereas after neutrons it decreased from the first to the second mitosis but then increased in the third mitosis. RBEs of 4.7, 4.8, and 7.4 were calculated for the corresponding mitoses. It was clearly demonstrated that new aberrations were produced after the first postradiation mitosis and expressed during the second and third mitosis. Chromosome loss also increased with increasing radiation dose at the second mitosis. An RBE of 2 was calculated for this effect. Comparing the presented data with previous investigations on embryonic and fetal death after prenatal irradiation, it was concluded that the high radiosensitivity of the one-cell embryo is due to the induction of structural as well as of numerical chromosome aberrations. PMID- 2900861 TI - Chromosome aberrations induced in human lymphocytes by an X-radiation accident: results of a 4-year postirradiation analysis. AB - After occupational and medical radiation exposures structural chromosome aberrations may be induced in the lymphocytes of the irradiated persons. Many authors have estimated the radiation dose from the yields of dicentric aberrations. We analysed the influence on the dicentric yield of increasing time intervals between irradiation and blood sampling from a person involved in an X radiation accident (radiography). During a 4-year follow-up we observed an approximately 7-fold decline of the dicentric yield up to the 25th month and thereafter an almost constant value. Since the decline did not commence until around the 10th month after the exposure, an exponential decrease of dicentric yield with time should be considered with reservation in this study, although it cannot be entirely ruled out. We conclude that in 'biological dosimetry' blood should be sampled as early as possible after the exposure. Furthermore, computation of 'half-times' of lymphocytes to allow for a delay in blood sampling seems uncertain after partial body exposures to high doses. Therefore in such cases dose estimates obtained 1 or more years after irradiation should be considered as minimum values. PMID- 2900862 TI - Radiation chemistry of d(TpApCpG) in oxygenated solution. AB - The radiation chemistry of the DNA tetranucleoside triphosphate d(TpApCpG) was investigated. The tetramer was X-irradiated in oxygenated aqueous solution and the various products separated by high-performance liquid chromatography. The principal modifications of the tetramer were analysed intact using nuclear magnetic resonance (NMR) spectroscopy and in some instances also by fast atom bombardment (FAB) mass spectrometry. The principal radiation-induced lesions of d(TpApCpG) were found to be a formamido modification derived from the thymine base, two stereoisomeric forms of a 1-carbamoyl-2-oxo-4,5-dihydroxyimidazolidine modification derived from the cytosine base and an 8-hydroxyguanine modification. PMID- 2900863 TI - Radicals produced by the reactions of SO4- with uridine and its derivatives. Studies by pulse radiolysis and gamma-radiolysis. AB - Using a pulse radiolysis technique, the sulphate radical, SO4-, has been demonstrated to react with uridine, 3'-UMP and 5'-UMP to produce intermediates of a new type, decaying according to a first-order rate law with k = 2.1, 4.1, 3.0 x 10(5) s-1 respectively at pH 7. The rate for uridine increases slightly with increasing pH. With deoxyuridine and 2', 3'-isopropylidene uridine, on the other hand, OH adduct radicals with longer lives (second-order decay) were found in accordance with the known fact that similar radicals are produced from N(1) methylated uracils with SO4-. On gamma-irradiation of similar solutions containing the substrates that produce such short-lived species, chain reactions and high yields of unaltered uracil were found. Some optical properties are detailed and a probable structure of the short-lived species is discussed in relation to the substituent effect at the 2' position of the sugar part and to its strong reducing ability revealed by the rapid reaction with TNM. PMID- 2900864 TI - Repair kinetics in mouse lung after multiple X-ray fractions per day. AB - The potential advantage for sparing normal tissue damage by hyperfractionation of low-LET radiation may be limited by the repair kinetics of tissues in the irradiated field. Tissues with slow repair kinetics will limit the number of fractions that may be given on the same day. Results are presented for mouse lung treated with a range of doses per fraction using either two or three fractions per day in multiple X-ray fractionation schedules. The results are analysed to determine whether the repair kinetics follow a single exponential function of time. The calculated repair rate (T1/2) was about 1.2 h for two fractions per day of 2 Gy (10F/5d) but slightly less (T1/2 = 0.8 h) for two fractions of 9 Gy (2F/1d). For smaller doses per fraction of 1.1 Gy, given three times per day (39F/13d), the T1/2 was not significantly less (T1/2 = 0.3-0.7 h). For three fractions per day of 1.1 Gy per fraction an unsatisfactory fit is achieved using a single exponential function of time, and a better fit is obtained using two components of repair. The repair kinetics are slow for lung, in comparison to acute reacting tissues (except skin), and may require that 6-8 h (i.e. four or five half-times) should be allowed between fractions on the same day so that more than 95 per cent of the repairable dose is repaired. At present the variation in repair kinetics with doses per fraction between 1.1 and 9 Gy are not significantly different, so no reduction of interfraction interval should be proposed. PMID- 2900865 TI - Structure of hydroxyl radical-induced DNA-protein crosslinks in calf thymus nucleohistone in vitro. AB - Hydroxyl radicals are known to produce DNA-protein crosslinks in chromatin in vivo and in vitro. Here we investigated DNA-protein crosslinks formed between aliphatic amino acids and thymine in calf thymus nucleohistone exposed predominantly to hydroxyl radicals in gamma-irradiated N2O-saturated aqueous solution. Aliphatic amino acids are the predominant types of amino acids in the core histones of calf thymus, and thus are likely to form crosslinks with DNA. For identification of the crosslinks we first investigated hydroxyl radical induced crosslinking of thymine to aliphatic amino acids in model systems, i.e. an aqueous mixture of thymine and a single amino acid. Samples were analyzed for possible thymine-amino acid crosslinks by gas chromatography-mass spectrometry. Using this approach the structure of the crosslinks was elucidated, and information on their gas chromatographic and mass spectral properties was obtained. Gas chromatography-mass spectrometry with selected-ion monitoring (GC MS/SIM) was then used to identify DNA-protein crosslinks in acidic hydrolysates of calf thymus nucleohistone exposed to ionizing radiation in buffered aqueous solution. DNA-protein crosslinks involving thymine and the amino acids Gly, Ala, Val, Leu, Ile and Thr were identified. In some cases several isomers of the same crosslink were observed. The yield of the crosslinks was measured by GC-MS/SIM and was found to be a linear function of radiation dose in the range 49 to 436 Gy. The mechanism for the formation of these DNA-protein crosslinks is thought to involve hydrogen atom abstraction by hydroxyl radicals from the aliphatic amino acid followed by addition of the amino acid radical to the carbon(6)-position of thymine and subsequent oxidation of the adduct radical. PMID- 2900866 TI - Modification of potentially lethal damage repair by some intrinsic intra- and extracellular agents: I. Proteinases and proteinase inhibitors. AB - The effects of nine intra- and extracellular proteinases and six proteinase inhibitors on the repair of potentially lethal damage (PLDR) induced by gamma rays in plateau-phase V79 cells were examined. It was demonstrated that these agents, which are intrinsic factors produced within mammalian cells, can modify PLDR activity. A stimulatory effect on PLDR was seen with calf liver neutral proteinase, and to a lesser extent, with inhibitor pepstatin A. Other proteinases which belong to serine, cysteine and aspartic superfamilies, as well as proteinase inhibitors, inhibited PLDR to different degrees. The effects of some of these agents, present during the PLDR period, on the rate of tritiated thymidine incorporation into the acid-insoluble cell fraction was also examined. They can modify the DNA synthesis of cells when subcultured from plateau phase for the assessment of colony-forming ability. There is no clear evidence that the effects observed are entirely attributed to the alteration of cellular proliferative processes. It seems more likely that many serine and cysteine proteinases and their inhibitors can adversely affect the PLDR process by modulating the activity of proteinase(s) and other enzymes involved more directly in PLDR because of interrelationships of the entire intracellular proteinase system. PMID- 2900868 TI - Charge potential of the 125Te daughter nuclide from 125I decay. PMID- 2900867 TI - Effect of free radicals induced by ultrasonic cavitation on cell killing. AB - The present study was undertaken to elucidate the mechanism of in vitro cell killing induced by 1.0 MHz continuous wave ultrasound at an intensity of 5.8 W/cm2. The chemical effects and mechanical effects arising from acoustic cavitation were determined by the amount of liberated iodine and the number of DNA double-strand breaks, respectively. The survival of mouse L cells immediately after irradiation was estimated by counting the number of cells which are not stained by trypan blue and the clonogenicity of surviving cells remaining immediately after irradiation was monitored by colony-forming ability. The effectiveness of the dissolved gases in liberating iodine was in the order O2 greater than Ar greater than N2 greater than N2O approximately 0. However, the effect of dissolved gases on the yield of double-strand breaks of DNA and on the two kinds of end points of cell killing was in the order O2 = Ar = N2 greater than N2O approximately 0. These results suggest that the different amounts of free radicals induced by ultrasound are not directly related to the ultrasonically induced cell killing. The presence of cysteamine (2 mmol dm-3) during sonication completely inhibited a decrease in clonogenicity of surviving cells, but did not inhibit that of cell survival immediately after sonication. These results suggest that the decrease of survival immediately after sonication is due to mechanical shear stress arising from cavitation, while the decrease of clonogenicity of the remaining surviving cells is due to free radicals induced by cavitation. The contribution of free radicals to total cell killing was estimated as about 1 per cent at the level of 95 per cent cell killing immediately after sonication. PMID- 2900869 TI - Re. Clonogenicity of the progeny of surviving cells after irradiation. PMID- 2900870 TI - Carrier detection in Japanese hemophilia A by use of three intragenic and two extragenic factor VIII DNA probes: a study of 24 kindreds. AB - The three factor VIII intragenic restriction fragment length polymorphisms (RFLPs), Bcll, Xbal, and Bgll and the two extragenic RFLPs, Bglll/DX13 and Taql/St14, were analyzed in 60 normal Japanese subjects and 24 families with hemophilia A. The allele frequencies were determined and the extent of linkage disequilibrium among the polymorphisms was assessed. In contrast to intragenic RFLPs of the factor IX gene, intragenic and extragenic RFLPs of the factor VIII gene in Japanese were similar to those observed in whites. As in whites, marked linkage disequilibrium severely compromised the value of the Bgll RFLP. The combination of the Bcll, Xbal, and Taql/St14 RFLPs gave 100% carrier detection in the hemophilia A families analyzed. PMID- 2900872 TI - Destruction of cell surface polarity by colchicine in rat salivary gland acinar cells: reevaluation of the microtubular function. PMID- 2900871 TI - Human fat cell beta-adrenergic receptors: beta-agonist-dependent lipolytic responses and characterization of beta-adrenergic binding sites on human fat cell membranes with highly selective beta 1-antagonists. AB - Beta-adrenergic receptors were characterized in human fat cell membranes using 125I-labeled cyanopindolol (125I-labeled CYP) and highly selective beta 1 antagonists. The iodinated radioligand bound saturably and specifically to a single class of high affinity binding sites. The number of binding sites determined with 125I-labeled CYP closely agreed with that determined with two other tritiated radioligands: [3H]dihydroalprenolol and [3H]CGP-12,177. Since 125I-labeled CYP does not discriminate between beta 1- and beta 2-adrenoceptors, the densities of the two receptor subtypes were determined from the competition curves of 125I-labeled CYP by highly selective beta 1-antagonists (bisoprolol, ICI-89,406, CGP-20,712A, and LK-204,545). Moreover, in order to enable correlation with binding data, the regulation of adenylate cyclase activity and of lipolysis was tested with various beta-agonist and antagonist compounds. The results obtained on fat cell membranes from abdominal subcutaneous adipose tissue demonstrated the following. 1) 125I-labeled CYP represents a valuable tool for the quantification and the delineation of beta-receptor subtypes. 2) The presence of sodium ions in binding buffers causes a modification of the affinity of beta sites for some beta-antagonists. 3) The human fat cell beta adrenergic receptor population defined by nonselective radioligands is composed of two subtypes that can be interpreted in terms of classic beta 1- and beta 2-adrenergic receptor subtypes as assessed by competition studies with highly selective antagonists; beta 2-sites are predominant (60-70% of 125I-labeled CYP sites) in the adipocytes of slightly overweight women. 4) Results support the idea that beta 1- as well as beta 2-adrenergic receptors are coupled with adenylate cyclase and involved in the induction of lipolysis. 5) The results focus on the interest in some beta 2 agonist drugs (zinterol, clenbuterol) as partial inductors of lipolysis, with the lipolytic efficacies of these compounds being well correlated with their efficacies at 125I-labeled CYP sites. PMID- 2900873 TI - [Treatment of the tall stature of Marfan disease with a delayed-action analog of somatostatin (SMS 201-995)]. PMID- 2900874 TI - Spatial learning potentiates the stimulation of phosphoinositide hydrolysis by excitatory amino acids in rat hippocampal slices. AB - Stimulation of phosphoinositide (PI) hydrolysis by excitatory amino acids (glutamate and ibotenate) or norepinephrine was potentiated in hippocampal slices from rats trained in an eight-arm radial maze, used as a test of spatial learning. No difference in basal or carbamylcholine-stimulated PI hydrolysis was found between control and trained animals. An increased PI response to excitatory amino acids and norepinephrine was not found in hippocampal slices prepared from animals trained in a shock conditioning avoidance test. These results suggest a possible involvement of specific glutamate receptors coupled with PI hydrolysis in the synaptic mechanisms underlying formation and/or storage of spatial memory. PMID- 2900875 TI - Selective protection of benzomorphan binding sites against inactivation by N ethylmaleimide. Evidence for kappa-opioid receptors in frog brain. AB - Selective binding of [3H]bremazocine and [3H]-ethylketocyclazocine to kappa opioid receptor sites in frog (Rana esculenta) brain membranes is irreversibly inactivated by the sulfhydryl group alkylating agent N-ethylmaleimide (NEM). Pretreatment of the membranes with kappa-selective compounds [ethylketocyclazocine (EKC), dynorphin (1-13), or U-50,488H] but not with [D Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO; mu specific ligand) or [D-Ala2,N-Me Phe4,Gly5-ol]enkephalin (DADLE; delta specific ligand) strongly protects the binding of the radioligands against NEM inactivation. These results provide more evidence for the existence of kappa-opioid receptors in frog brain. The relatively high concentrations of NEM that are needed to decrease the specific binding of [3H]bremazocine together with the observation of an almost complete protection of its binding sites by NaCl suggest that bremazocine may act as an opioid antagonist in frog brain. PMID- 2900876 TI - Muscarinic agonists evoke neurotransmitter release: possible roles for phosphatidyl inositol bisphosphate breakdown products in neuromodulation. AB - Carbachol (CCh), a muscarinic agonist that elicits the formation of inositol trisphosphate (IP3) and diacylglycerol (DG), induces a calcium-dependent [3H]norepinephrine ([3H]NE) release [IC50 = (2.7 +/- 0.5) X 10(-4) M] in rat brain slices. Similarly, other muscarinic agonists evoke [3H]NE release which is specifically inhibited by muscarinic antagonists such as 3-quinuclidinyl benzilate, atropine, and N-methyl-4-piperidyl benzilate. The atropine-sensitive evoked release is effectively inhibited by neomycin (IC50 = 50 microM), a phospholipase C inhibitor that interferes with IP3-dependent cellular processes. In addition, polymyxin B, a rather selective inhibitor of protein kinase C (PK C), abolishes the agonist-mediated release with a half-maximal effective concentration of 0.53 microM (750 ng/ml). These results have a significant implication for the mechanism by which agonists generating IP3 and DG act as inducers of neurotransmitter release in the CNS. However, since both neomycin and polymyxin B act also as N-calcium-channel blockers, other possible mechanisms are discussed. The CCh-induced release suggests that in the CNS an agonist-receptor interaction leads to a calcium-dependent neurotransmitter release, most likely via promoting the IP3/DG as second messengers followed by activation of PK-C. PMID- 2900877 TI - Restoration of catecholamine content of previously depleted adrenal medulla in vitro: importance of synthesis in maintaining the catecholamine stores. AB - The functional integrity of adrenal chromaffin storage vesicles was studied in the perfused rat adrenal gland subjected to intense exocytosis. Continuous perfusion with 55 mM K+-Krebs solution produced a large and uninterrupted secretion of catecholamines. Total amounts secreted within 45 min were 4.66 micrograms and represented almost 30% of the total tissue catecholamine content. If perfusion with excess K+ was extended to 90 min, the secretion increased further to 5.76 micrograms. Despite such a large secretory response, the catecholamine content of the K+-stimulated adrenal medulla was comparable to that of unstimulated control, suggesting an enhanced resynthesis to maintain the normal levels. Pretreatment of rats with alpha-methyl-p-tyrosine, and including this agent in the perfusion medium during stimulation with K+, caused a marked reduction in catecholamine content. The degree of depletion depended on the extent of stimulation with K+ (45% in 45 min and 60% in 90 min). Although depleted catecholamine stores did not show spontaneous recovery in 2 h, inclusion of tyrosine, L-3,4-dihydroxyphenylalanine or dopamine (but not epinephrine or norepinephrine) completely restored the catecholamine content of previously depleted adrenal medulla. Repletion achieved by tyrosine was time dependent (evident in 30 min and maximum in 2 h) and blocked by alpha-methyl-p-tyrosine but not by calcium deprivation. The ratio of epinephrine to norepinephrine remained constant during various stages of the experiment, suggesting both types of vesicles were equally affected by different treatments. The secretory response (10 Hz for 30 s) was unaffected even though tissue catecholamine stores were significantly depleted (50%). In summary, we have demonstrated that catecholamine content of the isolated perfused adrenal gland can be reduced by stimulation of exocytotic secretion in the presence of tyrosine hydroxylase inhibitor. Since the depleted stores can be fully refilled by synthesis of catecholamines from its precursors, it is suggested that chromaffin vesicles may be reutilized for the purpose of synthesis, storage, and secretion of adrenal medullary hormones. PMID- 2900878 TI - Astrocyte metabolism of [15N]glutamine: implications for the glutamine-glutamate cycle. AB - The metabolism of glutamine was studied in cultured astrocytes by incubating these cells with [2-15N]-glutamine and using gas chromatography-mass spectrometry to quantitate the transfer of 15N to other amino acids. We found that astrocytes simultaneously synthesize and consume [2-15N]glutamine, with the respective synthetic and utilization rates being approximately equal (ca. 13.0 nmol min-1 mg protein-1). Considerable 15N was transferred to alanine and a significant amount to the essential amino acids leucine, tyrosine, and phenylalanine, the latter process denoting active reamination of cognate ketoacids. A net export of alanine into the medium was noted. Astrocyte glutamine utilization appeared to be mediated via both the phosphate-activated glutaminase (PAG) pathway and the glutamine aminotransferase pathway, the activity of which was about half that of PAG. The glutamine concentration in the incubation medium determined whether net synthesis or utilization of this amino acid occurred. When glutamine was omitted from the medium, net synthesis occurred. When it was present at a high (5 mM) level, net consumption was observed. At a physiologic (0.5 mM) concentration, neither net synthesis nor consumption was noted, although the 15N data indicated that glutamine was actively metabolized. An implication of this work is that astrocytes clearly are capable of both synthesizing and utilizing glutamine, and current concepts of a glutamate-glutamine cycle functioning stoichiometrically between astrocytes and neurons may be an oversimplification. PMID- 2900879 TI - Glucose and synaptosomal glutamate metabolism: studies with [15N]glutamate. AB - The metabolism of [15N]glutamate was studied with gas chromatography-mass spectrometry in rat brain synaptosomes incubated with and without glucose. [15N]Glutamate was taken up rapidly by the preparation, reaching a steady-state level in less than 5 min. 15N was incorporated predominantly into aspartate and, to a much lesser extent, into gamma-aminobutyrate. The amount of [15N]ammonia formed was very small, and the enrichment of 15N in alanine and glutamine was below the level of detection. Omission of glucose substantially increased the rate and amount of [15N]aspartate generated. It is proposed that in synaptosomes (a) the predominant route of glutamate nitrogen disposal is through the aspartate aminotransferase reaction; (b) the aspartate aminotransferase pathway generates 2 oxoglutarate, which then serves as the metabolic fuel needed to produce ATP; (c) utilization of glutamate via transamination to aspartate is greatly accelerated when flux through the tricarboxylic acid cycle is diminished by the omission of glucose; (d) the metabolism of glutamate via glutamate dehydrogenase in intact synaptosomes is slow, most likely reflecting restriction of enzyme activity by some unknown factor(s), which suggests that the glutamate dehydrogenase reaction may not be near equilibrium in neurons; and (e) the activities of alanine aminotransferase and glutamine synthetase in synaptosomes are very low. PMID- 2900880 TI - Treating fearful dental patients: a practical behavioral approach. PMID- 2900882 TI - Catecholamine toxicity in cerebral cortex in dissociated cell culture. AB - Identification of endogenous toxins and characterization of the mechanisms by which toxins produce cell injury and death may help understand both normal modeling of cell populations and connections in the CNS as well as abnormal cell loss. The toxicity of catecholamines intrinsic to the CNS was investigated using the model system of rat cerebral cortex in dissociated cell culture. All catecholamines tested, including norepinephrine (NE), dopamine, and epinephrine, were toxic to neurons as well as glia at a concentration of 25 microM when added to cultures 24 hr after plating. Toxicity was evident after 48 hr exposure to NE, as monitored by loss of cells from the cultures. Toxicity did not seem to be mediated by adrenergic receptors because, although the beta-adrenergic agonist isoproterenol (but not the alpha-adrenergic agonist phenylephrine) was similar in its toxic effect to NE, the beta-adrenergic antagonist atenolol did not block the toxic effect of NE. Toxicity could be mimicked by hydrogen peroxide, a product of the oxidative degradation of catecholamines. Toxicity of NE was blocked by catalase. The neurotoxin 6-hydroxydopamine (6-OHDA), supposedly selective for catecholaminergic neurons, was found to be toxic over the same concentration range as NE. These results suggest that endogenous catecholamines may play a role in normal and abnormal cell death, and suggest that caution be used in relying on the specificity of 6-OHDA and other supposedly selective neurotoxins. PMID- 2900881 TI - Interactions between the lateral hypothalamus and the periaqueductal gray. AB - Anatomical and physiological experiments were conducted to characterize the interactions between the lateral hypothalamus (LH) and the periaqueductal gray (PAG) and to determine the role of neurotensin in their interaction. Anatomical studies using injection of Phaseolus vulgaris leucoagglutinin into the LH showed an extensive projection to the ventromedial and the ventrolateral PAG and a less dense projection to the medial and dorsal parts of this region. Physiological experiments were performed on both deeply and lightly anesthetized animals. Electrical stimulation of the LH caused excitation of PAG cells with an onset latency of approximately 14 msec. There was a strong correlation between the response of PAG cells to electrical stimulation and injection of glutamic acid into the LH. Electrical or chemical stimulation of the LH produced an increase in tail flick latency in the lightly anesthetized animals that outlasted the stimulation period. There was a strong correlation between the response of PAG cells to electrical and chemical stimulation of the LH and their response to pressure-injected neurotensin. It is concluded that an excitatory projection from the LH to PAG exists which may involve neurotensin. This pathway may be involved in the analgesia produced by LH stimulation. PMID- 2900884 TI - Increased intracellular levels of calcitonin gene-related peptide-like immunoreactivity in pulmonary endocrine cells of hypoxic rats. AB - The mammalian respiratory tract contains innervated groups of endocrine cells which are believed to respond to hypoxia. We have demonstrated the involvement of a specific regulatory peptide produced by the cells, calcitonin gene-related peptide (CGRP), in this response. Cells immunoreactive for CGRP or for protein gene product 9.5 (PGP 9.5), a general marker of nerves and endocrine cells, were quantified in sections of lungs from hypoxic (21 days, 10 per cent O2) and normoxic rats. An immunostaining method employing supra-optimal dilutions of primary antiserum was used. This detects variations in antigen concentration which may be masked if the routine, optimal dilution is used. The number of CGRP immunoreactive endocrine cells was significantly (P less than 0.001) greater in the lungs of hypoxic rats (76.9 +/- 10.1 cells/cm2, mean +/- SEM) compared with controls (19.7 +/- 2.4). However, the numbers of PGP 9.5-immunoreactive cells were the same in both groups (81.3 +/- 12.2, hypoxic; 79.5 +/- 9.8 control), suggesting that the total number of endocrine cells did not change. It is concluded therefore that the apparent increase in CGRP-immunoreactive endocrine cells in hypoxic rat lungs is due to increased intracellular levels of the peptide. Since CGRP is a vasodilator, this could have important implications in the vasoconstrictor response to hypoxia. PMID- 2900883 TI - Glutamate-positive corticocortical neurons in the somatic sensory areas I and II of cats. AB - Combined retrograde transport-immunocytochemical experiments were carried out on cats to study the morphology, laminar distribution, and percentages of corticocortical projecting neurons of somatosensory area I (SI) and II (SII) showing immunoreactivity to an antiserum raised against the amino acid glutamate (Glu). A previously characterized anti-Glu serum (Conti et al., 1987a, b; Hepler et al., 1987) was used in conjunction with HRP. This tracer was injected either in SI to label retrogradely neurons in ipsilateral SII (SII-SI association neurons) and contralateral SI (SI-SI callosal neurons) or in SII to label retrogradely neurons in ipsilateral SI (SI-SII association neurons) and contralateral SII (SII-SII callosal neurons). In sections from SI and SII processed for simultaneous visualization of Glu and HRP (Bowker et al., 1982), and containing the cells from which every one of the 4 corticocortical projections arise, 3 types of labeled neurons were observed: (1) single-labeled neurons showing the homogeneous brown immunoreaction product of Glu (Glu-positive neurons); (2) single-labeled neurons containing the granular black reaction product of retrogradely transported HRP (Glu-negative, association or callosal neurons); and (3) double-labeled neurons in which both the black HRP granules and the brown immunostaining were present (Glu-positive, association or callosal neurons). Double-labeled neurons were all pyramidal in shape and were distributed intermingled with Glu-negative corticocortical neurons in all layers of SI and SII known to give rise to association and callosal projections. Counts from 25 micron-thick sections showed that of 432 association and callosal neurons sampled from SI and SII, 214 (49.5%) were Glu-negative and 218 (50.5%) Glu-positive. In counts carried out on 5-micron-thick sections, the percentage of Glu-positive corticocortical neurons raised to about 70%. The 2 populations of single- and double-labeled corticocortical neurons showed no difference in their perikaryal cross-sectional areas. The present results show that a large fraction of association and callosal neurons of SI and SII are immunoreactive for Glu, and, therefore, these neurons probably use this excitatory amino acid, or a closely related compound, as neurotransmitter. PMID- 2900885 TI - Management of pediatric pain with opioid analgesics. AB - We have attempted to dispel many of the myths and misconceptions surrounding the use of narcotic analgesics in the treatment of childhood pain. Our hope is that an improved understanding and the application of effective, safe therapy will minimize the suffering of the child with acute or chronic pain. PMID- 2900886 TI - Phenylalanine hydroxylase expression in liver of a fetus with phenylketonuria. AB - The expression and activity of phenylalanine hydroxylase was studied in the liver of a fetus aborted after prenatal diagnosis of phenylketonuria. No phenylalanine hydroxylase enzymatic activity or immunoreactive protein was detectable in the PKU liver specimen, though both enzymatic activity and immunoreactive protein were detectable in control specimens of similar gestational age. Phenylalanine hydroxylase messenger RNA of normal size was present in the PKU fetal liver at normal abundance. These results confirm the genetic diagnosis of PKU in this fetus and indicate that the mutations in this fetus affect translation or stability of the phenylalanine hydroxylase protein. PMID- 2900887 TI - [Reactions and interactions of drugs]. PMID- 2900888 TI - Corneal permeability to bunazosin in rabbits. AB - Topical and systemic absorption of bunazosin after topical instillation was investigated in rabbits. Corneal permeability of bunazosin in vivo was increased by the addition of caprylic acid in amounts equimolar to bunazosin. Aqueous humor levels of bunazosin were significantly elevated. These results correlated well with those obtained in vitro experiments. Contrarily, the levels of plasma were not significantly affected and only slightly lowered by caprylic acid. PMID- 2900889 TI - Differential control of sympathetic fibres supplying hindlimb skin and muscle by subretrofacial neurones in the cat. AB - 1. Simultaneous recordings were made from postganglionic sympathetic fibres supplying hindlimb skin and skeletal muscle in chloralose-anaesthetized, artificially ventilated cats. Single-fibre activity was either isolated by dissection or discriminated from few-fibre preparations of fascicles in the left superficial peroneal or sural nerve (innervating hairy skin) and common peroneal nerve (innervating muscle). Vasoconstrictor fibres were identified by their spontaneous activity as well as their responses to stimulation of the lumbar sympathetic chain and to changes in baroreceptor activity. The baroreceptors were then denervated by bilateral section of the vagi, carotid sinus and aortic nerves. 2. In five cats, neurones in the region of the subretrofacial nucleus were activated chemically by microinjections of 2-10 nl 0.5 M-sodium glutamate from a micropipette inserted into the ventral surface of the medulla. Both skin and muscle vasoconstrictor fibres were activated by glutamate injections into this region on either side of the medulla. Arterial pressure also rose. 3. Glutamate injections at forty-two sites evoked a positive response, defined as an increase in cutaneous and/or muscle vasoconstrictor fibre activity of at least 25%. This response was evoked only in the cutaneous fibre at sixteen of these sites ('skin points'), only in the muscle fibre at seven sites ('muscle points'), and in both fibres in the remainder ('mixed points'). The largest percentage increases in activity of either type of fibre were obtained from mixed points. 4. The blood pressure rises following glutamate stimulation of muscle points were significantly greater than those produced by stimulation of skin points. Analysis of all positive responses showed that the evoked rise in blood pressure was significantly correlated with muscle sympathetic activity but not with cutaneous sympathetic activity. 5. Glutamate stimulation at different sites could evoke differential responses in skin and muscle vasoconstrictor fibres without any detectable change in the pattern of phrenic nerve discharge. 6. Skin points were grouped in the medial part of the subretrofacial region, and muscle points in the lateral part. In addition, for all positive responses there was a highly significant correlation between the ratio of muscle to cutaneous sympathetic activity evoked, and the distance from the mid-line of the corresponding injection site. 7. These results demonstrate a functional differentiation among subretrofacial neurones in their relative control of the sympathetic vasoconstrictor supply to skin and skeletal muscle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2900890 TI - Naloxone excites oxytocin neurones in the supraoptic nucleus of lactating rats after chronic morphine treatment. AB - 1. Lactating rats were implanted with a cannula in a lateral cerebral ventricle to deliver morphine (up to 50 micrograms/h) chronically from a subcutaneous osmotically driven mini-pump. After infusion of morphine for 5 days the rats were anaesthetized with urethane and prepared with ventral surgery for recording the electrical activity of single, antidromically identified neurones in the supraoptic nucleus. 2. A single I.V. injection of naloxone (5 mg/kg) in these rats provoked a long-lasting, large increase in intramammary pressure, but in control rats had negligible effects. Concentrations in plasma of oxytocin, measured by radioimmunoassay in samples of femoral arterial blood, rose from 44.7 +/- 2.5 to 1072.1 +/- 89.5 pg/ml (means +/- S.E.M.) 6 min after naloxone in the morphine-treated rats. In control rats, the concentration of oxytocin in plasma rose only from 42.1 +/- 2.9 to 125.1 +/- 28.2 pg/ml after naloxone. 3. Naloxone produced a transient increase in arterial blood pressure in morphine-treated but not control rats. Concentrations in plasma of vasopressin, measured by radioimmunoassay in samples of femoral arterial blood, rose in morphine-treated rats from 7.4 +/- 2.4 to 29.2 +/- 3.7 pg/ml after naloxone, but did not rise significantly in control rats. 4. Naloxone (1-5 mg/kg) produced a prompt and prolonged increase in the discharge rate of each of ten continuously active (putative oxytocin) cells recorded from ten morphine-treated rats. The discharge rate of the six cells tested at the highest dose (5 mg/kg) increased by an average of 6.3 Hz (360%) within 5 min, and the firing rate remained elevated for at least 30 min; the discharge rate of six continuously active supraoptic neurones recorded in control rats was not affected by naloxone. 5. The firing activity of five phasic (putative vasopressin) supraoptic neurones in morphine treated rats was increased for at least 30 min by the injection of naloxone; these increases were the result of a raised intraburst firing rate with no change in burst duration or frequency. One phasic neurone was inhibited for 15 min, and one phasic neurone was unaffected. 6. The excitatory effects of naloxone on neurones in the supraoptic nucleus of morphine-treated rats were not explained by changes in blood pressure or osmolarity and did not depend on suckling or a cholinergic pathway. 7. The concentrations of oxytocin in plasma and the operation of the milk-ejection reflex were similar in the controls and morphine treated rats, prior to naloxone. These findings indicate tolerance to initial inhibitory effects of morphine on oxytocin secretion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2900891 TI - The effects of vasoactive intestinal polypeptide on gastric motility in the lamb. AB - 1. Intra-arterial infusions of vasoactive intestinal polypeptide (VIP) were made in anaesthetized lambs in which activity of the reticulo-omasal orifice (ROO) was recorded manometrically and in conscious lambs in which activity of the reticulum, ROO and abomasum were recorded by electromyographic (EMG) techniques. 2. Spontaneous rhythmic opening and closing movements of the ROO occurred in anaesthetized lambs at 3-5 min-1. Infusions of VIP into the left gastric artery at rates of 0.5-3.0 nmol min-1 produced changes in activity of the ROO. Within 120 s of commencement of the infusions there was an increase in frequency and magnitude of the movements of the ROO for up to 120 s. This was followed with infusion of VIP at the lower levels (0.5-1.0 nmol min-1), by a marked reduction and sometimes complete loss of the rhythmic movements. There was always complete cessation of activity of the ROO with infusion of VIP at 1.5-3.0 nmol min-1. 3. In conscious lambs the frequency of the diphasic reticular EMG bursts which recur at intervals of ca. 1 min was not affected by infusions of VIP at 3.0 nmol min-1 for 10 min. 4. Between each diphasic reticular EMG burst in the conscious lamb there was normally phasic activity of the ROO consisting of EMG bursts of long (ca. 4 s) and short (ca. 1 s) duration. Within 90 s of commencement of infusion of VIP at 3.0 nmol min-1 short-burst EMG activity disappeared with the remaining long bursts being of greater duration (5.4 +/- 1.2 s) than before infusion. After a series of four to fifteen such more prolonged long bursts there was quiescence of the EMG of the ROO. After infusion of VIP EMG activity recommenced first as a series of eight to fourteen long bursts which was followed by the reappearance also of short-burst activity. Infusions of VIP at 8-10 nmol min-1 produced a more prompt cessation of EMG activity of the ROO. Of other peptides which were infused only PHI (a peptide with N-terminal histidine and C-terminal isoleucine amide) produced cessation of the EMG activity of the ROO. However, on a molar basis VIP was 2-3 times more potent than PHI in causing cessation of activity of the ROO. 5. Infusion of VIP at 3.0 nmol min-1 produced a cessation or diminution of EMG activity of the body, antrum and pylorus of the abomasum.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2900892 TI - Slow excitatory postsynaptic currents mediated by N-methyl-D-aspartate receptors on cultured mouse central neurones. AB - 1. Monosynaptic excitatory postsynaptic potentials (EPSPs) evoked between pairs of cultured neurones from either hippocampus or spinal cord were examined using the tight-seal whole-cell recording technique. 2. Using the selective N-methyl-D aspartate (NMDA)-receptor antagonist, 2-amino-5-phosphonovaleric acid (APV), two components of the EPSP could be resolved in cultures from both brain regions. The APV-sensitive (slow) component had the same latency, but a much slower time-to peak and longer duration than the APV-resistant (fast) component. Other NMDA antagonists such as ketamine also selectively blocked the slow component of the EPSP. 3. In Mg2+-free medium, the dual-component EPSP had a duration lasting up to 500 ms, greatly exceeding the membrane time constant of the postsynaptic neurone, suggesting that persistent activation of NMDA receptors was responsible for the long duration of the APV-sensitive component. 4. Under voltage clamp the excitatory postsynaptic currents (EPSCs) also showed fast and slow components, both of which had a reversal potential near 0 mV in physiological saline. The synaptic current could be fitted with a sum of two exponentials with a decay time constant for the slow EPSC near 80 ms. The slow current contributed approximately 50% of the total charge transfer during the EPSC. 5. In Mg2+-containing medium, the peak of the fast component was voltage insensitive, whereas the synaptic current measured at a latency of 10-50 ms was voltage dependent with a region of negative slope conductance at membrane potentials hyperpolarized to -30 mV. 6. Raising [Ca2+]o from 1 to 20 mM resulted in a shift of the reversal potential of the APV-sensitive component from near 0 mV to + 10 mV, but the reversal potential of the fast component remained near 0 mV. This suggests that conductances with different ionic permeability underlie the two components of the EPSC and that the slow component is highly permeable to Ca2+ as well as to monovalent cations. 7. Our results demonstrate that two functionally distinct excitatory amino acid receptor channels are simultaneously activated by transmitter release from a single presynaptic neurone. The conductance mechanism underlying the slow component of the EPSP displays the voltage dependence and Ca2+ permeability expected for NMDA-receptor channels. We suggest that the available conductance generating the slow EPSP may be sufficient, even at low firing rates, to influence excitability on both a short-term and more long-lasting basis. PMID- 2900893 TI - Synaptic connections in the dorsal cochlear nucleus of mice, in vitro. AB - 1. Intracellular recordings were made from the dorsal cochlear nucleus (DCN) in slices that contained the root of the auditory nerve and parts of the dorsal and ventral cochlear nuclei. Probably the largest and most common cells were impaled. 2. Weak shocks to the nerve usually evoked an excitatory postsynaptic potential (EPSP) that lasted about 90 ms and whose latency was often less than 1.2 ms, indicating monosynaptic input. 3. Stronger shocks elicited a larger EPSP and a later train of inhibitory postsynaptic potentials (IPSPs). Increasing the stimulus voltage shortened the latency of the train of IPSPs and increased its efficacy so that at large stimulus strengths inhibition dominated the synaptic response. 4. To determine whether any of the neuronal circuitry which generated the synaptic responses involved the ventral cochlear nucleus, recordings were made from slices containing only the dorsal nucleus. Synaptic responses to stimulation of the pial surface of the isolated DCN resembled those driven from the nerve root. That is, weak shocks evoked long-lasting, monosynaptic EPSPs and stronger stimuli elicited a larger EPSP followed by trains of IPSPs. The DCN, therefore, contains intrinsic inhibitory interneurones. 5. The parallel fibres of the DCN course superficially, near the stimulating electrodes, whereas the axons of the auditory nerve terminate in deeper areas. Thus, the monosynaptic EPSPs evoked from the pial surface are probably generated by parallel fibres. Apparently the inhibitory interneurones are also excited by a circuit including parallel fibres. 6. The putative neurotransmitter of parallel fibres, glutamate, excited all neurones tested. 7. Cells were sensitive both to glycine and to gamma aminobutyric acid (GABA). Only strychnine, however, not picrotoxin or bicuculline, blocked IPSPs. PMID- 2900894 TI - The effect of temperature on neuromuscular transmission in the main caudal artery of the rat. AB - 1. Excitatory junction potentials (EJPs) recorded in isolated segments of the proximal main ventral artery of the rat tail were reduced in amplitude and prolonged in time course as temperature was lowered from 35 to 15 degrees C. 2. The slow depolarization that followed the EJPs after supramaximal or repetitive perivascular stimulation was markedly slowed in time course, but little affected in amplitude, as temperature was lowered. 3. The time constant (tau EJP) of the exponential decay phase of the EJP recorded from cells deep in the media was similar to the membrane time constant, so that the increase in tau EJP at low temperatures is consistent with a decrease in membrane conductance. 4. The value of tau EJP was also prolonged if the EJP was evoked at the time of the peak of the slow depolarization; this effect was blocked by idazoxan (10(-7) M) but not by prazosin (10(-6) M). 5. During repeated short bursts of high-frequency stimulation, action potential initiation was facilitated by both the prolongation of EJPs and summation of slow depolarizations; these effects were greater at 25 than at 35 degrees C. 6. The interactions between EJPs and alpha-adrenoreceptor mediated membrane conductance changes are considered with respect to the electrical events occurring during sympathetic neuromuscular transmission at the natural temperatures of the rat tail. PMID- 2900895 TI - Cellular distribution, developmental changes and effects of cryptorchidism on uridine kinase in the rat testis. AB - High specific activity of uridine kinase was found in cultured peritubular cells (3.0 nmol/min per mg protein) which was more than 3-fold higher than that found in cultured Sertoli cells (0.79 nmol/min per mg protein). In the various classes of germ cells a decrease in specific uridine kinase activity was associated with increased maturity of the cells, primary spermatocytes, round spermatids and spermatozoa showing 1.3, 0.65 and 0.16 nmol/min per mg protein, respectively. A relationship between uridine kinase activity and the rate of RNA synthesis in these cells is suggested. A decrease in specific uridine kinase activity in testis with increasing age supports the finding of lower uridine kinase in mature germ cells than in earlier germ cells and somatic cells. This finding is further supported by the observation that cryptorchidism, which is associated with a time dependent depletion of germ cells, resulted in an increase in specific uridine kinase activity. The results indicate that pyrimidine salvage is important in earlier germ cells, as well as in somatic cells in the testis, to produce substrates for nucleic acid synthesis. PMID- 2900896 TI - Chronic muscle contraction headache: the importance of depression and anxiety. PMID- 2900897 TI - Substituted benzamides with conformationally restricted side chains. 2. Indolizidine derivatives as central dopamine receptor antagonists. AB - The substituted benzamides metoclopramide (1) and clebopride (3) are stimulants of gastric motility. They are also central dopamine receptor antagonists with 3 being the more potent. This is presumed to be due to an additional interaction of its N-benzyl group with the receptor. The effect of restricting the conformation of this group by replacing the N-benzylpiperidine side chain of 3 by phenyl substituted quinolizidines and indolizidines has been investigated. Only the indolizidines had significant activity, the nature of which depended upon the orientation of the phenyl substituent. The 2 alpha-phenyl isomers 5d-h were potent central dopamine D2 receptor antagonists with 5h showing selectivity for the limbic system. The 2 beta-phenyl isomer 5c was a gastric motility stimulant devoid of significant central dopamine receptor antagonist activity. Implications on receptor models are discussed. PMID- 2900898 TI - Retro-inverso concept applied to the complete inhibitors of enkephalin-degrading enzymes. AB - Peptide retro-inverso modification was applied to the complete hydroxamate inhibitors of the three zinc metallopeptidases (neutral endopeptidase 24-11 (NEP, EC 3.4.24.11), aminopeptidase N (APN, EC 3.4.11.2), and a dipeptidylaminopeptidase (DAP) involved in the in vitro enkephalin degradation by brain tissues. Compounds corresponding to the general formula RN(OH)CO(CH2)nCH(CH2Ph)NHCOCH(R')COOH (n = 0, 1) were synthesized. In the first series of inhibitors (n = 0), the "retro-inverso" modification induced a large decrease in inhibitory potency for NEP as compared to that of the parent compounds. In contrast, the presence of a methylene group between the hydroxamate and CH alpha in the second series (n = 1) led to derivatives with inhibitory potencies in the nanomolar range, similar to their analogues with a natural amide bond. On the other hand, the retro-inverso modification led to a slight improvement in the inhibition of DAP and APN, in the first series of inhibitors, while the inverse result occurred in the second series. Thus, compounds containing an alpha-amino acid moiety in P'1 position behave as weak inhibitors of the three enzymes, with IC50 values in the micromolar range, and compounds bearing a beta-amino acid moiety in the same position are more specific than the parent compounds for NEP inhibition. PMID- 2900899 TI - Structure-activity relationships among benextramine-related tetraamine disulfides. Chain length effect on alpha-adrenoreceptor blocking activity. AB - Several N'-substituted N,N''-(dithiodi-2,1-ethanediyl)bis(1, omega alkanediamines) were prepared and evaluated for their blocking activity on alpha adrenoreceptors in the isolated rat vas deferens and human blood platelets. The results were compared with those obtained for benextramine (N,N''-(dithiodi-2,1 ethanediyl)bis[N'-[(2-methoxyphenyl)-methyl]- 1 ,6- hexanediamine], 10). Bendotramine (N,N''-(dithiodi-2,1-ethanediyl)bis[N'-[(2-methoxyphenyl)- methyl] 1,12-dodecanediamine], 16) proved to be as active as 10 on alpha 1 adrenoreceptors, showing that optimum activity is associated with two carbon chain lengths separating inner from outer nitrogens of tetraamine disulfides. On the other hand, 16 had no activity up to 20 microM at alpha 2-adrenoreceptors. The optimum activity at this receptor subtype was associated with a six to eight carbon chain (10-12). Furthermore, 10 proved to be more selective toward alpha 2 adrenoreceptors whereas 16 was a selective alpha 1-antagonist. The tetraamine disulfides were shown also to be potent inhibitors of human platelet aggregation induced by ADP or epinephrine. The potency increased with the carbon chain length. However, the results on platelets did not parallel those found in the rat vas deferens, indicating that differences exist between the alpha-adrenoreceptor subtypes investigated. In conclusion, 10 may be a useful tool in characterizing alpha 2-adrenoreceptors whereas 16 might help in investigating alpha 1 adrenoreceptors. PMID- 2900900 TI - Role of the autonomic nervous system in reperfusion arrhythmias. PMID- 2900901 TI - Triazinate and platinum efficacy in combination with 5-fluorouracil and doxorubicin: results of a three-arm randomized trial in metastatic gastric cancer. Gastrointestinal Tumor Study Group. AB - The Gastrointestinal Tumor Study Group compared three regimens in a controlled prospectively randomized trial for the treatment of patients with advanced gastric cancer. All regimens contained 5-fluorouracil and doxorubicin (FA) but differed in the third drug: semustine (Me), triazinate (T), or cisplatin (P). FAT produced significantly superior overall survival (P less than .01) compared to FAMe. One-year survival rate for the FAT regimen was 30% compared to 15% for the FAMe regimen, and median survival times were 30 versus 24 weeks, respectively. The FAP regimen demonstrated a similar survival advantage compared to the FAMe regimen. The improved survival was observed despite decreased 5-fluorouracil and doxorubicin dosages for patients on the FAT and FAP arms. Severe toxicity rates were 42% for FAT, 69% for FAP, and 62% for FAMe. The FAT regimen produced significantly less hematologic toxicity than either FAP or FAMe, while mild neurotoxicity was the limiting toxicity of cisplatin in this study. Two classes of drugs, without known risks of potentially fatal long-term toxic effects, appear to be effective substitutes for long-acting alkylating agents such as Me or mitomycin in the treatment of advanced gastric cancer. These findings identify new approaches to therapy for this common disease. PMID- 2900902 TI - Abdominal polyorchidism: an unusual variant. AB - We describe an 18-month-old boy with polyorchidism in whom both ipsilateral testes were located intra-abdominally. To our knowledge no prior reports have documented a similar case in the literature to date. This case has important implications pertaining to the treatment of intra-abdominal cryptorchid testes. Intra-abdominal polyorchidism and its management are discussed briefly. PMID- 2900903 TI - Role of Escherichia coli adhesins in urethral colonization of catheterized patients. AB - Escherichia coli is a major cause of catheter-associated urinary tract infection and frequently colonizes the urethra prior to invading the urinary tract. Bacterial pili, filamentous protein cell surface-associated appendages, have been shown to mediate colonization of epithelial cells. Pili associated adhesins can be detected in vitro by their ability to mediate bacterial hemagglutination of erythrocytes. We have assessed the role of bacterial adhesins in supporting urethral colonization by determining the hemagglutination reactions of 56 E. coli isolates from the urethra of patients with indwelling urethral catheters. The adhesin detected most frequently was the type 1 mannose-sensitive hemagglutinin (43%), and 43% of isolates failed to hemagglutinate guinea pig or human erythrocytes. E. coli hemagglutinins were no more common on urethral isolates from patients that were persistently colonized (E. coli present 70% of the time catheterized), than from those that were transiently colonized (E. coli present 30% of the time catheterized). Analysis of the HA reactions and DNA plasmid profiles of multiple isolates from persistently colonized patients suggested that the E. coli strain colonizing the urethra changed over time. The data suggest that bacterial colonization of the urethra is mediated in part by adhesins and changes over time. PMID- 2900904 TI - Infections with Francisella tularensis biovar palaearctica in hares (Lepus timidus, Lepus europaeus) from Sweden. AB - The occurrence of tularemia was studied in 1,500 hares submitted to the National Veterinary Institute, Uppsala, Sweden for postmortem examination during 1973 through 1985. A total of 109 tularemia cases was recorded based on the fluorescent antibody (FA) test for Francisella tularensis and on the gross and microscopic pathology. Tularemia was diagnosed only in the varying hare (Lepus timidus) and not in the European brown hare (Lepus europaeus). The geographical distribution of the 109 cases indicates that tularemia has not spread in Sweden during the last 45 yr, with the exception of an endemic occurrence of the disease on the island of Stora Karlso in the Baltic sea. The disease was most frequent in the autumn and only a few cases were recorded during winter. Cases were not seen in the spring. The annual prevalence varied, with several cases in 1974 and 1981, but there were no cases in 1976 and 1980. The postmortem findings in hares dying of tularemia in the autumn were characterized by focal coagulative necrosis in liver, spleen and bone marrow, with high numbers of bacteria FA-positive for F. tularensis. In hares dying during winter months, the most characteristic findings were hemorrhagic enteritis and typhlitis, although necrotic lesions could occur in liver, spleen and bone marrow. Diseased hares on the island of Stora Karlso were demonstrated to be infected with ticks, while hares on the mainland of Sweden generally were fed upon by mosquitoes. Twenty-six of the 109 hares with tularemia were examined bacteriologically and F. tularensis biovar palaearctica was isolated from eight. The lung extract antibody test for F. tularensis was performed in 18 of the 109 hares. All were negative. In addition to the field study, an experimental study with F. tularensis biovar palaearctica was performed. Four varying hares and three European brown hares were inoculated. None of the hares died from tularemia, and generalized infection was not demonstrated. PMID- 2900905 TI - [Epidural anesthesia for a patient with Takayasu arteritis]. PMID- 2900906 TI - [Concepts and future prospects in HTLV-I-associated myelopathy]. PMID- 2900907 TI - Prevalence of hepatitis B markers, antibodies to adult T cell leukemia/lymphoma virus and antibodies to human immune deficiency virus in prostitutes in Fukuoka, Japan. AB - Prevalence of hepatitis B (HB) markers, antibodies to human T cell leukemia virus (HTLV-1) and antibodies to human immune deficiency virus 1 (HIV-1) in prostitutes working in Fukuoka city were studied. Sera were collected from 237 prostitutes during January-September, 1986. Among them, 9 (3.8%) were HB virus surface antigen (HBs Ag) positive, of whom, 3 were HBe antigen positive and the remaining 6 were anti-HBe positive. The positive rate of anti-HBs was 34.2%. The incidence of anti-HTLV-1 in the prostitutes was 5.9%. These incidences are considered to be within the usual range in Kyushu district. No seropositive case for anti-HIV was found. PMID- 2900908 TI - Effects of caffeine on gluconeogenesis and urea synthesis induced by alpha adrenergic stimulation in suspensions of rat hepatocytes. AB - Effects of caffeine on gluconeogenesis and urea synthesis of rat isolated hepatocytes were investigated in the presence of hormonal agonists. Phenylephrine at 10 microM stimulated 1.7-fold gluconeogenesis and 1.9-fold (compared to control) urea synthesis from 4 mM glutamine. Stimulative effects of caffeine in the range from 0.1 to 10 mM were biphasic depending on its concentration, and it showed maxima at about 1 mM. Caffeine at 1 mM stimulated 2.1-fold gluconeogenesis and 2.4-fold urea synthesis. Caffeine without phenylephrine did not stimulate both syntheses. These effects of caffeine and phenylephrine diminished in the absence of extracellular Ca2+. Results on uptake of 45Ca2+ into hepatocytes and change in quin-2 fluorescence indicated that phenylephrine induced Ca2+ influx into the cell and consequently increased the intracellular Ca2+ concentration, [Ca2+], and that the addition of caffeine did not further stimulate the effect of phenylephrine on [Ca2+]. Therefore, we suggest that stimulation of gluconeogenesis and urea synthesis by phenylephrine is due to increase in [Ca2+]. Since caffeine is known to inhibit phosphodiesterase, the additional stimulation of both syntheses by caffeine plus phenylephrine may be due to the synergistic effect of increases in cAMP and [Ca2+]. The increase in the rates of gluconeogenesis and urea synthesis similarly depended on the caffeine concentration. Furthermore, the ratio of [acetoacetate]/[3-OH-butyrate] which shows intramitochondrial redox state, also depended on the caffeine concentration, indicating a possible coupling of the redox function of mitochondria with [Ca2+]. PMID- 2900909 TI - Different responses to beta-adrenoceptor blocking drugs of the blood pressure and heart rate in the urethane-anesthetized dog and rat. AB - I.v. propranolol (Prop) produced sustained pressor responses in rats but not in dogs under urethane anesthesia. In the dogs there was a progressive reduction in systolic blood pressure (SBP) in accordance with a significant heart rate (HR) reduction. Even at the i.v. dose (5 mg/kg) where vasoconstrictor response to i.v. norepinephrine (NE) is changed to the vasodilator one in rats, phenoxybenzamine could not completely suppress the NE-induced vasoconstriction in dogs. In pithed dogs, unlike pithed rats, i.v. Prop augmented neither sympathetic nerve stimulation- nor i.v. epinephrine (Epi)-induced pressor responses. Urethane anesthesia brought much higher concentrations in plasma Epi and NE in the dog than in the rat. In comparison with their respective values under the conscious state, SBP and HR of the dog were higher and those of the rat were lower under urethane anesthesia. As in urethane-anesthetized dogs, i.v. Prop elicited remarkable HR reduction accompanied by progressive hypotension in coronary ligated rats with high sympathetic activity. Thus the reason for the absence of pressor response to beta-receptor blockage in the dog may be due to less functional significance of beta 2-adrenoceptor-mediated vasodilation in determining the peripheral vascular tone; and also, the possibility that there may be the involvement of an inverse influence of urethane on the cardiovascular regulatory system in terms of enhancing sympathetic nervous activity in the dog and a decreasing one in the rat can not be ruled out. PMID- 2900910 TI - [Effect of clopheline on thrombocyte aggregation]. AB - Data on clopheline effect on platelet aggregation, both spontaneous and ADP- or adrenaline-induced, in normal donors are reported. Clopheline is shown to slightly increase aggregation in normal subjects, exhibiting properties of a weak aggregation inductor. Where adrenaline is present in the aggregating system, clopheline undermines its platelet aggregation-inducing effect and, consequently, shows properties of a more competitive antagonist, as compared to adrenaline. PMID- 2900911 TI - A simple and rapid method to screen for mutant mice lacking D-amino-acid oxidase activity. AB - A simple and rapid method to screen for mutant mice (Mus musculus) lacking D amino-acid oxidase activity has been devised. Mice were given water containing small amounts (0.02%) of either D-methionine or D-phenylalanine. Urinary levels of the D-amino acid were examined using thin-layer chromatography. Some mice excreted substantial amounts of the D-amino acid through the urine. None of them had detectable D-amino-acid oxidase activity. PMID- 2900912 TI - Neuropeptide Y: a candidate neurotransmitter for biliary motility. AB - Neuropeptide Y (NPY) is a recently discovered polypeptide found in neurons throughout the gastrointestinal tract and in especially high concentrations in the biliary tree. This study was designed to test the functional significance of these high concentrations in the biliary tree by determining the effect of intravenous NPY on sphincter of Oddi and gallbladder motility. In adult male prairie dogs a side-hole, pressure-monitored perfusion catheter was placed through a choledochotomy into the duodenum and positioned in the sphincter of Oddi. A perfusion catheter was also placed in the gallbladder fundus. Sphincter of Oddi and gallbladder pressures were recorded before and during intravenous infusions of NPY at doses of 10, 100, and 500 ng/kg/min. Each dose was administered to seven separate animals. No effects were seen at the 10 or 100 ng/kg/min doses. NPY at the 500 ng/kg/min dose significantly increased sphincter of Oddi phasic wave frequency, amplitude, and motility index (MI = F X A). In addition, gallbladder pressure was significantly increased after 20 min of intravenous infusion of NPY at the 500 ng/kg/min dose. No significant changes in blood pressure were noted. These data suggest that in the prairie dog, systemic intravenous infusion of NPY significantly increases sphincter of Oddi phasic wave activity and gallbladder pressure. These findings are similar to those observed with intravenous cholecystokinin but opposite of those seen with peptide YY in this species. We hypothesize that neuropeptide Y may be an important neurotransmitter or neuromodulator regulating bile flow. PMID- 2900913 TI - A new method for determination of in vivo pA2 using infusions of naloxone to steady-state blood concentrations. AB - A method is described for the measurement of pA2 in vivo for the opioid antagonist naloxone, infused to predicted steady-state blood concentrations in rats. The method has been applied to antagonism of the respiratory depressant effects of opioid agonists. The basis of the technique rests upon determination of the plasma clearance of the antagonist whence appropriate loading doses and zero order infusion rate constants are calculated. The predicted concentrations of naloxone were verified by direct plasma measurement. Using the infusion protocol pA2 determinations by Schild analysis were significantly different from those obtained by bolus injection. The approach described provides more accurate estimates of in vivo pA2 and could be applied to other antagonists, species, and biological responses, overcoming many of the problems inherent in the use of bolus antagonist dosing, which is currently widely employed. PMID- 2900914 TI - Effects of bicuculline on the changes of pain threshold and some neurotransmitters of brain in rats induced by EAA. PMID- 2900915 TI - Human T-cell leukemia virus type I (HTLV-I) and blood transfusion. AB - Human T-cell leukemia (or T-lymphotropic) virus type I (HTLV-I) is a human exogenous infectious retrovirus of the family Retroviridae. This virus has been associated with adult T-cell leukemia and endemic myelopathies (tropical spastic paraparesis and HTLV-I associated myelopathy). HTLV-I is transmitted by sexual contact, from mother to child, by intravenous drug abuse, and by blood transfusion. The estimated lifetime risk of developing disease in antibody positive patients is 1 in 80, and a latency period as long as 20 years can intervene. No case of transfusion-transmitted disease has been reported to date. Currently, no testing of blood donors for HTLV-I is required in the United States, and no such test has been approved by the Food and Drug Administration. Because data on the natural history of this virus may take years to accumulate, it is probably wise to begin excluding anti-HTLV-I-positive units from the blood supply in the United States as soon as a licensed test is available. PMID- 2900916 TI - A cytostatic drug (taxol) which does not inhibit monocyte phagocytosis. AB - Taxol is a new cytotoxic agent which arrests cell division in the G2 and the M phases, due to its unique property of inhibiting microtubule function by stabilization. In contrast to other microtubule antagonists except griseofulvin, taxol did not inhibit monocyte phagocytosis. It is suggested that lack of interference with the function of mature leukocytes may reduce the immunosuppression induced by a cytotoxic agent. PMID- 2900917 TI - Diagnosis of alcoholism. AB - Alcoholism is among the most prevalent of the difficult diseases to establish diagnoses in medicine. This article outlines a number of steps to help in identifying the alcoholic patient. These include: a careful history, several laboratory blood tests, simple paper-and-pencil tests, and recognition of alcohol related medical disorders. PMID- 2900918 TI - Effects of ethyl loflazepate (CM 6912) on sleep in normal humans. AB - The effects of 2 mg and 4 mg of ethyl loflazepate (CM 6912), a new anxiolytic benzodiazepine, on sleep were studied in 12 healthy male subjects. Polygraphic recordings were made for 6 consecutive nights from each subject. An inert placebo was given on the first 3 nights and on the sixth night, and 2 mg or 4 mg of CM 6912 was administered on the fourth and fifth nights to 6 subjects, respectively. The drug and placebo were administered orally 30 min after supper, and the record of polysomnograms started at 22:30 hr and continued until the natural awakening of the subjects the next morning. The polysomnograms were evaluated by computerized automatic analysis using the method of interval histogram. Both doses of CM 6912 increased total sleep time, and reduced sleep latency and total awakening in a dose-dependent manner. Both doses slightly decreased stage 1 sleep, significantly increased stage 2 sleep, but slightly decreased stages 3, 4 and REM sleep. These changes continued into the sixth recovery night. No obvious changes were observed in subjective assessments after administration of CM 6912. These results suggest that CM 6912 is an efficacious compound and has minimal adverse effects on sleep. PMID- 2900919 TI - Trial of tissue plasminogen activator for mortality reduction in acute myocardial infarction. Anglo-Scandinavian Study of Early Thrombolysis (ASSET). AB - 13,318 patients admitted to fifty-two coronary care units with suspected acute myocardial infarction were considered for inclusion in a double-blind study comparing recombinant tissue-type plasminogen activator (rt-PA) 100 mg plus heparin with placebo plus heparin. 8307 (62%) were excluded, mainly because their symptoms had begun more than 5 h previously, but all excluded patients were followed up at least until hospital discharge. 2516 patients were randomly allocated to rt-PA and 2495 to placebo. At one month the overall case fatality rates were 7.2% and 9.8%, respectively, a relative reduction of 26% (95% confidence interval 11-39%). 6.3% of patients given rt-PA had a bleeding complication (1.4% major) compared with 0.8% given placebo (0.4% major). However, the incidence of stroke was similar--1.1% in the rt-PA group and 1.0% in the placebo group. Subset analysis showed that patients who had a normal electrocardiogram (ECG) at the time of randomisation (17.5% of the whole trial population) had a low case fatality rate (1.6% in those given rt-PA compared with 3.0% in those given placebo). In those with an abnormal ECG at entry, rt-PA was associated with a 24.5% relative reduction in 1 month fatality (95% confidence interval 9-37%). PMID- 2900920 TI - Microalbuminuria as predictor of vascular disease in non-diabetic subjects. Islington Diabetes Survey. AB - The relation between urinary albumin excretion rate (AER) and vascular disease was studied in 187 subjects aged over 40 selected from 1084 cases attending a diabetic screening project. AER exceeded 20 micrograms/min in 3 of 13 newly diagnosed diabetic subjects (23%) and 16 of 171 non-diabetic subjects (9.4%). There was a weak relation between AER and both systolic and diastolic blood pressures. Coronary heart disease was found in 54 of 164 (32.9%) subjects with AER of 20 micrograms/min or less and in 14 of 19 (74%) with AER above this. Peripheral vascular disease was present in 16 of 165 (9.7%) subjects with AER of 20 micrograms/min or less and 8 of 18 (44%) with a high AER. Logistic regression, including diabetes, impaired glucose tolerance, systolic and diastolic blood pressures, smoking, age, sex, ethnic origin, and body mass index, demonstrated the independence of this relation between AER above 20 micrograms/min and coronary heart disease (odds ratio [OR] 6.38, 95% confidence interval 1.91-21.4) and peripheral vascular disease (OR 7.72, 2.14-27.8). After a mean of 3.6 (SD 0.19) years, 167 subjects (89.3%) were traced. There had been 9 deaths, 3 (2.0%) among 149 subjects with normal AER and 6 (33%) among 18 microalbuminuric subjects (OR 24.33, 5.40-109.7). PMID- 2900921 TI - Cerebral anaerobic glycolysis and reduced cerebral oxygen transport in human cerebral malaria. AB - In 12 patients comatose with cerebral malaria, cerebral blood flow was 52.2 (SE 4.0) ml/100 g per min, within the reported range for healthy controls, but cerebral vascular resistance was raised at 1.66 (0.19) mm Hg/ml per 100 g per min. Cerebral oxygen consumption (1.90 [0.23] ml/100 g per min), and cerebral arteriovenous oxygen content difference (3.5 [0.43] ml/dl) were subnormal, while cerebral venous pO2 (5.7 [0.2] kpA) was raised. After recovery of consciousness there were significant decreases in arterial lactate concentration (2.44 [0.45] to 1.19 [0.45] mumol/l) and cerebral lactate production (17.4 [7.9] to 5.6 [1.1] mmol/100 g per minute). These results provide evidence of cerebral anaerobic glycolysis associated with inadequate oxygen delivery to the brain consistent with either inhibition of cerebral oxidative metabolism or the microcirculatory obstruction envisaged in the "mechanical" hypothesis for cerebral malaria. PMID- 2900922 TI - Detection of HIV1 DNA in infants and children by means of the polymerase chain reaction. AB - The polymerase chain reaction (PCR) assay was used to investigate the possibility of HIV1 DNA detection in uncultured peripheral blood mononuclear cells from newborn infants and children of HIV-infected mothers. HIV1 DNA sequences were detected in mononuclear cells of six of fourteen symptom-free newborn infants of seropositive mothers. Only one of these infants had detectable HIV antigenaemia. In addition, HIV1 DNA was identified in the mononuclear cells of five of ten children (2-5 years old) of infected mothers who had become seronegative 12-15 months after birth; among these, four children had only mild clinical features related to HIV infection, while the other had none. HIV1 DNA was shown in all of eight seropositive children with HIV infection and none of fifteen normal seronegative controls. The PCR assay thus provides an early and direct identification of HIV infection in newborn infants and seronegative children born to infected mothers. PMID- 2900923 TI - Effect of fenamates on prostaglandin E receptor binding. AB - The effect of fenamates on prostaglandin E receptor binding was examined in myometrial samples collected at hysterectomy. Sodium meclofenamate and mefenamic acid inhibited binding of PGE2 to its specific receptor in a dose-dependent manner, with an ED50 of 20 mumol/l and 200 mumol/l, respectively. PMID- 2900924 TI - Catheter and wire guided endoscope exchange for biliary stents. PMID- 2900925 TI - Retinoids and control of cutaneous malignancy. PMID- 2900926 TI - Fatigue. PMID- 2900928 TI - Benign familial haematuria. PMID- 2900927 TI - Biochemical assessment of birth asphyxia. PMID- 2900929 TI - The right to die. PMID- 2900930 TI - Recurrent pulmonary oedema in hypertension due to bilateral renal artery stenosis: treatment by angioplasty or surgical revascularisation. AB - 11 patients with atheromatous renovascular hypertension had a history of multiple episodes of pulmonary oedema. 7 had stenosis of both renal arteries, 2 had stenosis of the artery to a solitary kidney, and 2 had unilateral stenosis with an intact contralateral kidney. Successful revascularisation (by angioplasty in 8, and surgery in 3) improved blood pressure and renal function, and virtually eliminated pulmonary oedema. In a second series of 55 consecutive patients with azotaemia and renovascular hypertension, pulmonary oedema occurred in 13 (23%). Blood pressure and renal function were not significant predictors of pulmonary oedema, but coronary heart disease and bilateral (vs unilateral) renal artery stenosis were. Bilateral renal artery stenosis may be a specific and treatable predisposing factor to pulmonary oedema in azotaemic hypertensive patients. PMID- 2900931 TI - Diagnosis and management of dysentery by community health workers. AB - To develop guidelines for community health workers in the treatment of patients with diarrhoea, diarrhoea prevalence was actively surveyed for a year in a remote rural community of 915,000 persons, and the enteric pathogens and clinical features associated with diarrhoeal illness were determined in a sample of 300 patients. Bloody diarrhoea accounted for 39% of all diarrhoea episodes and 62% of diarrhoea-associated deaths. 51 (50%) of 101 patients with a history of bloody diarrhoea had Shigella infection, compared with 31 (16%) of 199 patients with other types of diarrhoea. A history of bloody diarrhoea was as predictive of the presence of shigella infection (positive predictive value 50%, negative predictive value 86%) as more complex prediction schemes incorporating other clinical features or stool microscopic examination. In the area of Bangladesh where the study was done reduction of diarrhoea-related morbidity and mortality will depend on control and treatment of shigellosis, and community health workers have been instructed to provide antibiotics for patients with a history of bloody dysentery. PMID- 2900932 TI - Choice of non-steroidal anti-inflammatory drug in persons treated for dyspepsia. AB - Prior use of analgesics among 1327 new users of cimetidine over the age of 65 at Group Health Cooperative of Puget Sound was much more common than among 5308 members of similar age and sex who had never taken cimetidine. The excess included not only most non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin, but also extended to paracetamol. New users of cimetidine who had not received analgesics in the preceding 2 years were preferentially given recently introduced NSAIDs if an NSAID was subsequently prescribed. Review of prior studies of analgesic use and ulcer diseases reveals a regular association between ulcer and preceding use of paracetamol, a drug for which no causal association to ulcer is thought to exist. General increases in use of analgesics by elderly dyspeptic patients may have given rise to artefact in reported associations between manifestations of ulcer disease and NSAIDs. PMID- 2900934 TI - Tamoxifen as risk factor for carcinoma of corpus uteri. PMID- 2900933 TI - Inadvertent nuclear war. PMID- 2900935 TI - Intrathecal beta-interferon in multiple sclerosis. PMID- 2900936 TI - Frusemide and prevention of bronchoconstriction. PMID- 2900937 TI - Parkinson's disease after antithyroid treatment. PMID- 2900938 TI - Clobazam for epilepsy. PMID- 2900940 TI - Use of midazolam in children. PMID- 2900939 TI - Familial polyposis coli. PMID- 2900941 TI - Glyceryl trinitrate in skin necrosis caused by extravasation of parenteral nutrition. PMID- 2900942 TI - Management of oral bleeding in haemophilic patients. PMID- 2900943 TI - Human parvovirus B19 infection in pregnancy. PMID- 2900944 TI - Management of ectopic pregnancy. PMID- 2900945 TI - Spontaneous abortion and assisted conception. PMID- 2900946 TI - Deletion of blood mitochondrial DNA in pancytopenia. PMID- 2900947 TI - Thalidomide for severe acute graft-versus-host disease. PMID- 2900948 TI - Haloperidol and cardiac arrest. PMID- 2900949 TI - Cytomegalovirus matching in renal transplantation. PMID- 2900950 TI - Death from hyperglycaemic ketoacidosis in a man with no history of diabetes. PMID- 2900951 TI - HTLV-I and malignant hypereosinophilic syndrome. PMID- 2900952 TI - Defective handling of mycobacteria. PMID- 2900954 TI - Almitrine and peripheral neuropathy. PMID- 2900953 TI - Persistence of heptachlor in serum of people consuming contaminated dairy products. PMID- 2900955 TI - New method specific for acetylcholinesterase in cerebrospinal fluid: application to Alzheimer's disease. PMID- 2900956 TI - Hyponatraemia and hypo-osmolality. PMID- 2900958 TI - "Doctor" in Europe. PMID- 2900957 TI - New treatment for urethral strictures. PMID- 2900959 TI - Koryagin and psychiatric coercion. PMID- 2900960 TI - Medical defence and insurance. PMID- 2900961 TI - The 1987 Athens heatwave. PMID- 2900962 TI - Seroconversion to HIV-1 negative regulation factor. PMID- 2900964 TI - Lung-sound transmission and reliability of chest signs. PMID- 2900963 TI - Acute meningoencephalitis on dose reduction of zidovudine. PMID- 2900965 TI - Fundus fluorescein angiography in adult respiratory distress syndrome. PMID- 2900966 TI - Potentially fatal splenic involvement in infective endocarditis. PMID- 2900967 TI - Postoperative wound scoring. PMID- 2900968 TI - Carboplatin or cisplatin? PMID- 2900969 TI - Campylobacter enteritis during doxycycline prophylaxis for malaria in Thailand. PMID- 2900970 TI - Platelet serotonin concentration in patients with finger-clubbing. PMID- 2900971 TI - Anti-LEA1 monoclonal antibody and bone marrow graft rejection in adults. PMID- 2900972 TI - Pathogenesis of haemolytic uraemic syndrome. PMID- 2900973 TI - Spontaneous adverse reaction reporting in the elderly. PMID- 2900974 TI - Three anaesthetic deaths. Leaving the anaesthetised patient. PMID- 2900976 TI - Too great expectations. PMID- 2900975 TI - BMA view on HIV prevalence screening. PMID- 2900977 TI - Effects of routine one-stage ultrasound screening in pregnancy: a randomised controlled trial. AB - 4997 of 7354 pregnant women had no clinical indication for an elective ultrasound examination at 12 weeks' gestation. 2482 of these women were randomly selected for ultrasound screening at 15 weeks and the remainder received the same standard antenatal care without the scan. Labour was less often induced among screened women both for all reasons (5.9% vs 9.1%, p less than 0.0001) and for suspected post-term pregnancy (1.7% vs 3.7%, p less than 0.0001). Earlier detection of twins had no effect on neonatal outcome. Among babies born to screened women, fewer were of birthweight less than 2500 g (59 vs 95, p = 0.005) and mean birthweight was 42 g higher (p 0.008). For babies born to screened women who smoked it was 75 g higher (p 0.012) and for those of non-smokers 26 g (not significant). The reason for the differences in mean birthweight could be that screened women reduced smoking in response to watching their fetus on the scan. PMID- 2900978 TI - Oesophageal ischaemia in motility disorders associated with chest pain. AB - The cause of chest pain in diffuse oesophageal spasm and "nutcracker" oesophagus is not clear. Spasm of the oesophageal muscle itself is probably not the cause, because pain and spasm are frequently not coincident. It is suggested instead that oesophageal ischaemia may be the cause of the pain, since the rewarming rate of the oesophagus after a standardised cold challenge was significantly longer in 9 patients with these motility disorders than in 21 normal controls. As rewarming time in other sites correlates with blood flow, these results are consistent with the hypothesis that the oesophagus is ischaemic in these patients. PMID- 2900979 TI - Direct detection of HIV RNA expression in seropositive subjects. AB - The polymerase chain reaction (PCR) and reverse transcription were used to assess human immunodeficiency virus type 1 (HIV1) RNA expression in peripheral blood mononuclear cell samples from seropositive subjects. HIV RNA was detected from seropositive subjects who had no symptoms, lymphadenopathy syndrome, and acquired immunodeficiency syndrome. DNA PCR of the samples used for RNA extraction showed that seventeen of eighteen (94%) contained HIV proviral DNA. Eleven (65%) of the seventeen DNA-positive samples were also positive for HIV RNA, including samples from four patients undergoing antiviral drug treatment. Serum HIV antigen assays detected only six (32%) of the nineteen PCR-positive samples. Owing to the speed and high sensitivity of PCR for HIV detection, this technique will be suitable for monitoring antiviral therapy and the virus load of people with HIV infections. PMID- 2900981 TI - Mutation in cystatin C gene causes hereditary brain haemorrhage. AB - Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disorder in which a cysteine proteinase inhibitor, cystatin C, is deposited as amyloid fibrils in the cerebral arteries of patients and leads to massive brain haemorrhage and death in young adults. A full length cystatin C cDNA probe revealed a mutation in the codon for leucine at position 68 which abolishes an Alu I restriction site in the cystatin C gene of HCCAA patients. The Alu I marker has been used to show that this mutation is transmitted only in affected members of all eight families investigated, and that the mutated cystatin C gene causes HCCAA. PMID- 2900980 TI - Failure of second-look laparotomy to influence survival in epithelial ovarian cancer. AB - The survival benefit of second-look laparotomy after completion of primary chemotherapy in patients with epithelial ovarian cancer has been assessed in a prospective randomised trial of 166 patients. Patients were randomised into three groups. All were initially treated with cisplatin (100 mg/m2 x 5) after primary laparotomy. Group A (n = 53) was scheduled to have a second-look laparotomy, followed by cyclical oral chlorambucil. Group B (n = 56) was scheduled to have a second-look laparotomy, followed by total abdominal and pelvic irradiation, and group C (n = 57) received oral chlorambucil as for group A but had no second-look operation. With a median follow up of 46 months (range 21-64), no differences in survival were noted between the three groups. The median survival for group A was 21 months (95% CI 11-31 months), for group B 15 months (11-19), and for group C 17 months (8-26). Thus second-look laparotomy after completion of first-line single-agent cisplatin chemotherapy did not confer any survival benefit on patients with epithelial ovarian cancer. PMID- 2900983 TI - Ovalocytosis and malaria. PMID- 2900982 TI - BSE and scrapie: agents for change. PMID- 2900984 TI - Bedside detection of intracardiac shunts. PMID- 2900985 TI - Are insect repellents safe? PMID- 2900986 TI - Disposal of the previable fetus. PMID- 2900987 TI - Sports medicine--is there lack of control? PMID- 2900988 TI - Oxford screening programme for abdominal aortic aneurysm in men aged 65 to 74 years. AB - 824 men aged 65 to 74 were invited for ultrasound screening of the aorta and 426 (51.7%) attended. An abdominal aortic aneurysm was discovered in 23 (5.4%), and in 10 (2.3%) the aneurysm was 4.0 cm or more in diameter. 2 other patients had a common iliac artery aneurysm. The 36 men who had objective evidence of occlusive arterial disease of the lower limbs were twice as likely to be tobacco smokers and accounted for 5 (20%) of the aneurysms discovered. Extension of this screening programme to England and Wales could be expected to identify 52,500 men with an abdominal aortic aneurysm. If elective surgical replacement of the aneurysm were to be accepted by 60% of those with aneurysms 4 cm or more in diameter, 6000 unnecessary deaths from aortic aneurysm rupture could be prevented. PMID- 2900989 TI - Family outbreaks of psittacosis in Israel. AB - Eight family outbreaks of clinical or subclinical psittacosis in Israel after exposure to infected birds were studied. Throat cultures for Chlamydia psittaci and serological tests for Chlamydia species, including strain TWAR, were obtained from 37 people. Cloacal smears and cultures of internal organs for C psittaci were taken from 9 dead birds. 62% of the people studied had symptoms, and 67% of the birds that died had previously been sick. Evidence for acute C psittaci infection was found in 81% of patients (30/37). Diagnosis was established in 22 by isolation of the causal organism from throat cultures and in 8 by positive IgM serology (reciprocal titre greater than or equal to 8) with evidence of acute seroconversion or clinical findings compatible with the disease, or both. No serological evidence for acute TWAR infection was found. All birds studied had microbiological evidence of C psittaci infection, and most had abnormal findings on necropsy. PMID- 2900990 TI - Youth and the threat of nuclear war. The psychological task of venturing into unknown territory. PMID- 2900992 TI - Nottingham study of neurotic disorder. PMID- 2900991 TI - Indigenised pharmaceuticals in developing countries: widely used, widely neglected. PMID- 2900993 TI - Diagnosis and treatment response in "functional" psychosis. PMID- 2900994 TI - Gamma-interferon and chronic fatigue syndrome. PMID- 2900995 TI - Astemizole-induced torsade de pointes. PMID- 2900996 TI - Thunderclap headache. PMID- 2900997 TI - Exploding head. PMID- 2900999 TI - Syncope, vomiting, and migraine. PMID- 2900998 TI - Successful treatment of prosthetic heart-valve thrombosis with high short-term doses of streptokinase. PMID- 2901000 TI - Simple signs and acute respiratory infections. PMID- 2901001 TI - Ethambutol and the eye. PMID- 2901002 TI - Predicting insulin-dependent diabetes. PMID- 2901003 TI - Treatment of essential thrombocythaemia by alpha-interferon. PMID- 2901004 TI - Diagnostic value of plasma D-dimer in suspected pulmonary embolism. PMID- 2901005 TI - Safety of bovine somatotropin. PMID- 2901006 TI - Immunosuppressive therapy and Sneddon's syndrome. PMID- 2901007 TI - Leukaemia in young children in Scotland. PMID- 2901008 TI - Antibody to both human herpesvirus 6 and cytomegalovirus. PMID- 2901009 TI - Natural history of early gastric cancer. PMID- 2901010 TI - 2-Amino-3 (methylamino)-propionic acid in cycad-derived foods is an unlikely cause of amyotrophic lateral sclerosis/parkinsonism. PMID- 2901011 TI - HLA antigen splits for kidney matching. PMID- 2901012 TI - New role for the serum bactericidal test. PMID- 2901013 TI - Surveillance for stage 1 non-seminomatous germ cell testicular tumours--a potential threat to employment? PMID- 2901014 TI - Importance of electrocardiography for coronary risk factor surveys. PMID- 2901015 TI - Mortality reduction in ISIS-2 too optimistic because of unstable angina? PMID- 2901016 TI - In-situ hybridisation for detection of cytomegalovirus in liver from patients after marrow grafting. PMID- 2901017 TI - Measurement of cardiac output. PMID- 2901018 TI - Acute volume loading, atrial natriuretic peptide release and cardiac function in healthy men. Effects of beta-blockade. AB - Release of ANP is dependent on right atrial distension and pressure, which in turn are dependent on both venous return and left ventricular function. These two latter parameters are both modulated by beta-receptors. In the present study, the effects of selective beta-blockade vs non-selective beta-blockade on hypertonic volume expansion induced changes in ANP release and systemic hemodynamics were assessed in 8 healthy normotensive male volunteers. On placebo, infusion of hypertonic saline (1200 ml of 2.5% NaCl) caused an intravascular volume expansion of 10-11%, and small non-significant increases in cardiac performance (LVEDV, SV, or CI), but it provoked a 2-fold increase in plasma ANP. Beta-blockade by either atenolol or propranolol blunted the increase in cardiac volume load (reflected by LVEDV) as compared to placebo, but did not affect the ANP response to volume expansion. The increase in ANP correlated closely with the intravascular volume expansion on placebo and to a lesser extent on beta-blockade. In healthy men, therefore, intravascular volume expansion that caused only small changes in cardiac activity, resulted in clear increases in release of ANP. Inhibition of the increase in cardiac volume load by beta-blockade did not interfere with ANP increase, suggesting a role for extra-cardiac receptors in the release of ANP or a change in the pressure/volume relationship. PMID- 2901019 TI - Effects of morphine and opioid peptides on plasma levels of atrial natriuretic peptide. AB - The effect of opiate ligand administration on plasma levels of atrial natriuretic peptide (ANP) was studied in awake, freely moving Sprague-Dawley rats. Prior to and following the intracerebroventricular (icv) or central venous (iv) injection of morphine (MS), leu-enkephalin (Leu-enk), dynorphin (Dyn) or beta-endorphin (B endor), plasma samples were obtained for measurement of ANP concentrations by radioimmunoassay. MS was 10 times more potent when given icv than when given iv to increase plasma ANP levels. Icv injection of Leu-enk decreased plasma ANP concentrations. Dyn and B-endor administration (iv or icv) did not alter the plasma concentration of ANP. These effects of MS and Leu-enk on plasma concentrations of ANP appear to be mediated through actions on the central nervous system. MS, Leu-enk, B-endor, and Dyn given icv, produced elevations of plasma norepinephrine (NE) and epinephrine (Epi) concentrations. When MS was given icv, mean Epi and NE plasma levels increased 10-50 times the increases noted with B-endor, Leu-enk and Dyn. A role of catecholamines in mediating MS stimulated ANP release is supported by the observation that ganglionic blockade with chlorisondamine significantly attenuated the increase of plasma ANP levels. MS, but not B-endor, Leu-enk and Dyn, acts within the brain to increase plasma levels of ANP. MS-induced elevations of plasma ANP levels may be dependent on an intact autonomic nervous system. PMID- 2901020 TI - Influence of D-1 receptor system on the D-2 receptor-mediated hypothermic response in mice. AB - The hypothermia induced by apomorphine, a mixed dopamine (DA) agonist in male Swiss-Webster mice, was not blocked by the selective D-1 antagonist SCH 23390 but was completely blocked by the selective D-2 antagonists haloperidol, sulpiride and YM-09151-2. The selective D-1 agonist SKF 38393 did not elicit hypothermic response but the selective D-2 agonist quinpirole caused a marked lowering of rectal temperature. D-2 antagonists blocked this response to quinpirole. SCH 23390 enhanced and SKF 38393 attenuated the hypothermia induced by quinpirole. Ineffective doses of haloperidol and SKF 38393, when given together, completely blocked the effect of quinpirole. It was concluded that hypothermia is a D-2 receptor mediated response but modulated by the D-1 receptor system. In another series of experiments the influence of neuroleptics and antidepressants on the hypothermic effect of apomorphine and quinpirole was investigated. The hypothermic effect of a low dose (1 mg/kg) of apomorphine was blocked by the D-2 receptor antagonists, but not by classical antidepressants. However, the response to a high dose (10 mg/kg) of apomorphine was blocked by both classical antidepressants and D-2 antagonists (except haloperidol). These drugs did not show similar effect on quinpirole-induced hypothermia. It is clear that the hypothermic response, especially that of quinpirole, is not a suitable model for testing either neuroleptics or antidepressants. PMID- 2901021 TI - An improved and rapid HPLC-EC method for the isocratic separation of amino acid neurotransmitters from brain tissue and microdialysis perfusates. AB - An improved, HPLC with electrochemical detection method for the isocratic separation and determination of amino acids from post-mortem brain tissue and from microdialysates of awake-behaving animals is described. Optimal conditions that maximize stability, resolution, and sensitivity were determined for the pre column derivatization of amino acids using o-phthalaldehyde and B mercaptoethanol. Ten different amino acids including aspartate, glutamate, taurine, tyrosine and GABA were effectively resolved within 18 min. Tissue measurements from caudate, globus pallidus and substantia nigra showed regional variations in amino acid content. Microdialysis of the striatum yielded significant amounts of all amino acids examined, including GABA, from only 25 microliter of perfusate. PMID- 2901022 TI - Feeding elicited by dynorphin (1-13) microinjections into the ventral tegmental area in rats. AB - Both the endogenous opioid peptide, dynorphin (1-13) (DYN), and morphine elicited dose-dependent feeding when microinjected into the ventral tegmental area of food satiated rats. DYN was 50,000 times more potent than morphine in producing feeding. Whereas the ED50 for morphine was in the nanomole range, the ED50 for DYN was in the femtomole range. Administration of a narcotic antagonist attenuated DYN-elicited feeding. These data suggest a possible role for DYN in the VTA in opioid modulation of feeding behavior. PMID- 2901023 TI - Differences in the time course of haloperidol-induced up-regulation of rat striatal and mesolimbic dopamine receptors. AB - Regional differences in the onset and persistence of increased dopamine D2 receptor density in rat brain were studied following daily injections of haloperidol for 3, 7, 14, or 28 days. Striatal [3H]-spiroperidol Bmax values were significantly increased following 3-28 days of haloperidol treatment, as compared to saline controls. Olfactory tubercle Bmax values were significantly increased only after 14 or 28 days of haloperidol treatment. Nucleus accumbens Bmax values were significantly increased only in the 14-day drug treatment group, suggesting that dopamine D2 receptor up-regulation in nucleus accumbens may reverse during ongoing neuroleptic treatment. These findings suggest that important differences in adaptive responses to chronic dopamine blockade may exist between dopaminergic synapses located in various rat brain regions. PMID- 2901024 TI - [Medical workers of Ulyanovsk Province during World War II]. PMID- 2901025 TI - Circadian monitoring of gastric juice mutagenicity. AB - The circadian monitoring of intragastric pH and of the mutagenicity of 440 gastric juice samples collected hourly from 22 subjects provided evidence that, irrespective of diagnosis and treatment, a weak yet consistent increase in revertants can be detected in his- Salmonella typhimurium strains during the 3-4 h periods following each meal. The recorded mutagenic activity was not related to the histidine content of gastric juice, was due to thermostable components and was not significantly inhibited by administration of vitamin C. Various genetic mechanisms were involved, which were different from those consequent to the artificial supplementation of gastric juice with sodium nitrite. Treatment with a histamine H2-receptor antagonist (famotidine), either at dinner or at bedtime, was followed by a nocturnal plateau of mutagenicity. However, such effect was not due to mutagenicity of the drug or of its derivatives, but to the therapeutic rise in pH associated with its antisecretory activity. PMID- 2901026 TI - Characterization of an epithelial, nearly diploid liver cell strain, from Chinese hamster, able to activate promutagens. AB - Epithelial liver cells of the Chinese hamster (CHEL cells) were propagated in culture for 35 passages. At favourable cell densities, the population doubling time in normal medium, was 20 h. L-Tyrosine amino transferase activity was retained at a measurable level, but its enhancement by dexamethasone was detected solely in cells of early passages. Pyruvate kinase was strongly activated by fructose-1,6-biphosphate at low substrate concentrations. These enzymatic properties suggest that the CHEL cells are derived from a sub-population of parenchymal hepatocytes or from cells closely related to parenchymal hepatocytes. With a lag period of a few hours, CHEL cultures metabolized benzo[a]pyrene. In cell homogenates the various monooxygenase activities investigated were below the detection limits. However, other xenobiotic-metabolizing activities, such as cytochrome P-450 reductase, glutathione transferase and UDP-glucuronosyl transferase were high, with levels comparable to those observed in freshly isolated rat parenchymal cells. Epoxide hydrolase activity was also detected, but was lower than in the liver. The CHEL cells were able to activate benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene and aflatoxin B1 to mutagens, as shown in a co culture assay with V79 cells, in which acquisition of resistance to 6-thioguanine was studied. At early passages, the CHEL cells had a near diploid set of chromosomes. Then, gradually the frequency of cells with slight changes in the number of chromosomes and the frequency of tetraploids were increased. During the observation period (up to passage 20) the modal number of chromosomes shifted from 22 to 23. No gross morphological changes in the cultures were noticed during the 20 passages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901027 TI - [Spreading of the virus of hemorrhagic fever with renal syndrome among small mammals of a meadow-field complex and its epidemiological significance]. PMID- 2901029 TI - Effects of thiol-reagents on [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4 propionic acid binding to rat telencephalic membranes. AB - The binding of [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA), a ligand for the quisqualate subtype of excitatory amino acid receptors, was measured after chemical modifications of rat brain synaptic membranes. Treatment with oxidizing or thiol-alkylating agents did not modify [3H]AMPA binding, whereas treatment with several sulfhydryl reagents produced marked increases in binding. The involvement of free sulfhydryl groups in the regulation of the properties of [3H]AMPA binding sites was suggested by the specificity of p-chloromercuribenzoic acid (PCMB), its sulfonate analog p chloromercuriphenyl-sulfonic acid (PCMBS), and HgCl2, plus the reversal of their effects after reduction with dithiothreitol. Pretreatment of synaptic membranes with the oxidizing agent 5,5'-dithiobis(2-nitrobenzoic acid) or the alkylating agent N-ethylmaleimide did not significantly affect [3H]AMPA binding but markedly reduced the enhancing effect of PCMBS. On the other hand, the increase in [3H]AMPA binding produced by PCMBS was not prevented by treatment with agonists such as quisqualate or L-glutamate and was produced equally well in resealed postsynaptic membranes with both lipophilic or nonlipophilic SH-reagents. Using filtration assays, two types of binding sites could be detected with high and low affinity for [3H]AMPA. Treatment with SH-reagents produced an increase in the Bmax for the high affinity component and a decrease in the Bmax for the low affinity component, accompanied by an increase in its affinity for the ligand. Using centrifugation assays, the same two types of sites could be detected under control conditions but treatment with SH-reagents produced an increase in affinity of the large component that prevented the analytical differentiation of the two sites. Treatment with SH-reagents also increased the binding of [3H] glutamate to the N-methyl-D-aspartate receptors but did not modify the binding of [3H]kainate to the kainate receptors or the strychnine-insensitive [3H]glycine binding. These results suggest that free sulfhydryl groups allosterically modulate the affinity of the quisqualate subtype of excitatory amino acid receptors and also indicate that different types of glutamate receptors might be differentially affected by chemical modification. PMID- 2901028 TI - Pilins of Bacteroides nodosus: molecular basis of serotypic variation and relationships to other bacterial pilins. PMID- 2901030 TI - The effect of lysosomotropic agents and secretory inhibitors on anthracycline retention and activity in multiple drug-resistant cells. AB - The effect of lysosomotropic agents and secretory inhibitors were compared with verapamil for their effect on the activity of doxorubicin (DOX) in multiple drug resistant (MDR) P388 leukemia cells (P388R) and in blocking anthracycline efflux from these cells. Agents known to interact with the plasma membrane did not potentiate DOX activity in P388R cells unless these same agents were also capable of interacting with acidic compartments within the cell. The lysosomotropic detergent Triton WR-1339, for example, potentiated DOX activity in P388R cells and stimulated the net accumulation of daunorubicin (DAU) in P388R cells by inhibiting drug exodus. However, another detergent, deoxycholate, and two membrane active antibiotics, amphotericin B and filipin, had no effect on DOX activity and/or DAU efflux in P388R cells. Lysosomotropic agents such as chloroquine and secretory inhibitors such as monensin, cytochalasin B, and vinblastine all inhibited DAU efflux from P388R cells. In a MDR B16 melanoma cell line, the activity of DOX was potentiated by both verapamil and reserpine. These same two agents also inhibited melanin secretion from this same cell line. Based on these observations, we propose that secretory vesicles derived from the Golgi apparatus might be involved in the MDR phenomenon. We further suggest that drugs such as DOX might be concentrated in these acidic vesicles, where they would be released to the outside of the cell by exocytosis. PMID- 2901031 TI - Differential sensitivity of HTC and Fu5-5 cells for induction of tyrosine aminotransferase by 3',5'-cyclic adenosine monophosphate. AB - The two independently derived hepatoma cell lines (HTC and Fu5-5) have previously been shown to display different sensitivities for the induction of tyrosine aminotransferase (TAT) enzyme activity and mRNA levels by glucocorticoids with the enzyme being half-maximally induced at approximately 7-fold higher concentrations of dexamethasone in HTC cells than in Fu5-5 cells. In the present study we investigated the induction of TAT activity by cAMP in order to see whether the difference is limited to the steroidal induction. Using the stable cAMP derivative (8-(4-chlorophenylthio)-cAMP) as an inducer, we found that a 6 fold higher cAMP concentration was needed in HTC cells to achieve the same extent of enzyme induction as in Fu5-5 cells. The induction of TAT enzyme activity could be accounted for by an increased amount of TAT mRNA. Further experiments involving sequential addition of both inducers in general showed a synergism of steroids and cAMP for TAT induction in HTC cells only at submaximal concentrations of steroid; in Fu5-5 cells, the occurrence of synergism depended on the order of addition of inducers. The maximal response in HTC cells was limited to the value that could be achieved by induction with steroid alone. In Fu5-5 cells, however, the steroid response could be augmented when cAMP was added to cells already maximally induced by steroid. This demonstrates that the effect of a combination of cAMP and steroids depends on their concentration, the sequence of their addition, and the rat hepatoma cell line used. Collectively the data suggest that a common pretranslational event determines the differential sensitivity of TAT induction by glucocorticoids and by cAMP in HTC and Fu5-5 cells. Furthermore a second, or possibly the same, common event also regulates the maximum level of TAT induction that is obtainable under most conditions with glucocorticoids and/or cAMP. PMID- 2901032 TI - Structural organization and regulation of the chicken estrogen receptor. AB - We have cloned the chicken estrogen receptor (ER) from a chicken oviduct lambda gt11 library using the human ER cDNA sequence. This chicken ER sequence is virtually identical to the recently published sequence. One noteable difference is an amino acid change from glutamine to arginine located toward the central region of the sequence. The size of the ER protein predicted from the 589 amino acids is approximately 66,000 which fits well with the range of molecular weights previously published for the calf uterine and human ER (65,000-70,000). We observed the size of the chicken ER mRNA to be approximately 7.8 kilobases which is in agreement with the previously published size of 7.5 kilobases. In vivo secondary stimulation of chicken oviduct total RNA with diethylstilbestrol does not induce chicken ER mRNA. A time course following the chicken ER mRNA levels after secondary stimulation with diethylstilbestrol indicated a decrease in mRNA levels 8 h after DES administration. A similar study was performed using progesterone for the secondary stimulation. An increase in the chicken ER mRNA levels was observed 24 h after stimulation with progesterone. Two regions of very high homology were delineated by analyzing the sequence of this chicken ER cDNA and comparing it to the sequences of the human ER, human glucocorticoid, and chicken progesterone receptors and the P75-erbA fusion product of the avian erythroblastosis virus. The first concensus region is 72 amino acids in length and the second region of high homology is 62 amino acids long. Detailed comparisons of these regions for the steroid hormone receptors and v-erb A are presented. Possible functions for the individual regions of high homology are discussed. PMID- 2901033 TI - Developmental regulation of somatostatin gene expression in the brain is region specific. AB - Developmental regulation of somatostatin (SRIF) gene expression was studied in five regions of rat brain and in rat stomach. Total RNA was isolated from hypothalamus, cortex, brainstem, cerebellum, and olfactory bulb, as well as stomach at eight stages of development from prenatal day 16 to postnatal day 82. Hybridization of a 32P-labeled rat SRIF cDNA probe to Northern blots of total RNA from the above tissues during development demonstrated a single hybridizing band approximately 670 base pairs in length. When SRIF mRNA levels from each stage of development were quantified and normalized by the amount of poly (A)+ RNA present at that stage of development, a unique pattern of SRIF gene expression was seen in each region. In brainstem and cerebellum, SRIF mRNA levels peaked early in development between prenatal day 21 and postnatal day 8 and then declined until postnatal day 82. Hypothalamus and cortex, on the other hand, showed a progressive increase during development with peak levels occurring between postnatal days 13 and 82. In contrast, stomach and olfactory bulb showed SRIF mRNA levels which were low during early development and which rose late in development (postnatal days 13 to 82). Marked differences in the amount of SRIF mRNA within each region were present as well. These data suggest that there is differential expression of the SRIF gene in different regions of the brain and in the stomach during development. Further study of this phenomenon may provide insight into the in vivo control of SRIF gene expression and the role of SRIF in the developing brain. PMID- 2901034 TI - Nervous and immune system cooperation during newt limb regeneration. A new look on old problems. PMID- 2901035 TI - Mutagenicity of amino acid and glutathione S-conjugates in the Ames test. AB - The mutagenicity of the glutathione S-conjugate S-(1,2-dichlorovinyl)glutathione (DCVG), the cysteine conjugates S-(1,2-dichlorovinyl)-L-cysteine (DCVC) and S (1,2-dichlorovinyl)-DL-alpha-methylcysteine (DCVMC), and the homocysteine conjugates S-(1,2-dichlorovinyl)-L-homocysteine (DCVHC) and S-(1,2-dichlorovinyl) DL-alpha-methylhomocysteine (DCVMHC) was investigated in Salmonella typhimurium strain TA2638 with the preincubation assay. DCVC was a strong, direct-acting mutagen; the cysteine conjugate beta-lyase inhibitor aminooxyacetic acid decreased significantly the number of revertants induced by DCVC; rat renal mitochondria (11,000 X g pellet) and cytosol (105,000 X g supernatant) with high beta-lyase activity increased DCVC mutagenicity at high DCVC concentrations. DCVG was also mutagenic without the addition of mammalian activating enzymes; the presence of low gamma-glutamyltransferase activity in bacteria, the reduction of DCVG mutagenicity by aminooxyacetic acid, and the potentiation of DCVG mutagenicity by rat kidney mitochondria and microsomes (105,000 X g pellet) with high gamma-glutamyltransferase activity indicate that gamma-glutamyltransferase and beta-lyase participate in the metabolism of DCVG to mutagenic intermediates. The homocysteine conjugate DCVHC was only weakly mutagenic in the presence of rat renal cytosol, which exhibits considerable gamma-lyase activity, this mutagenic effect was also inhibited by aminooxyacetic acid. The conjugates DCVMC and DCVMHC, which are not metabolized to reactive intermediates, were not mutagenic at concentrations up to 1 mumole/plate. The results demonstrate that gamma glutamyltransferase and beta-lyase are the key enzymes in the biotransformation of cysteine and glutathione conjugates to reactive intermediates that interact with DNA and thereby cause mutagenicity. PMID- 2901036 TI - Metabolism of phospholipids and lysophospholipids by Trypanosoma brucei. AB - African trypanosomes (Trypanosoma brucei brucei) rapidly metabolize exogenous 1 acyl-lysophospholipids by at least two routes: (1) hydrolysis by a phospholipase A1; (2) acylation by an acyl-CoA-dependent acyltransferase. In contrast to lysophospholipids, exogenous phospholipids are not rapidly metabolized by T. brucei. The acyltransferase (EC 2.3.1.23) converts exogenous 1-acyl lysophosphatidylcholine and exogenous acyl-CoA to phosphatidylcholine and CoA-SH. It is a membrane-bound enzyme and shows maximal activity within the first 2 min of exposure of trypanosomes to the exogenous substrates. The acyltransferase specificity for lysophospholipids is lysophosphatidylcholine greater than lysophosphatidylinositol greater than lysophosphatidylethanolamine greater than lysophosphatidate. Phosphatidylcholine enhances the enzyme activity towards lysophosphatidylethanolamine and lysophosphatidic acid. The preference for CoA acyl thioesters is oleoyl greater than palmitoyl greater than myristoyl greater than stearoyl greater than arachidonoyl, and this specificity distinguishes the protozoan enzyme from those of cells of mammalian hosts, which are specific for arachidonoyl-CoA. When the acyltransferase converts exogenous lysophosphatidylethanolamine to phosphatidylethanolamine, the latter is rapidly methylated to form dimethylphosphatidylethanolamine. There is also rapid hydrolysis of exogenous oleoyl-CoA by a thioester hydrolase in living trypanosomes, to yield free oleate and CoA-SH. PMID- 2901037 TI - Combination adjuvant chemotherapy for node-positive breast cancer. Inadequacy of a single perioperative cycle. AB - We studied the timing and duration of adjuvant chemotherapy for operable breast cancer with axillary-node involvement in a randomized trial including 1229 patients divided into three treatment groups. One group received a single perioperative course of adjuvant combination chemotherapy beginning within 36 hours of mastectomy; a second received six cycles of conventionally timed adjuvant chemotherapy starting 25 to 32 days after operation; and a third received both the perioperative cycle and the conventionally timed regimen. The chemotherapy consisted of cyclophosphamide, methotrexate, and fluorouracil. Tamoxifen was added to the conventionally timed regimen in postmenopausal women. At a median follow-up of 42 months, the estimated four-year disease-free survival was 40 percent for the single perioperative cycle, 62 percent for the longer, conventionally timed regimen, and 60 percent for the combined program (P less than 0.0001). Overall survival differences also favored the longer treatments (P = 0.011). We conclude that a single perioperative cycle of adjuvant combination chemotherapy is less effective than prolonged therapy in patients with operable breast cancer and involved axillary nodes. Furthermore, starting the prolonged therapy perioperatively is no more effective than starting treatment four weeks after mastectomy. PMID- 2901038 TI - P-glycoprotein in acute nonlymphoblastic leukemia and in the blastic crisis of myeloid leukemia. PMID- 2901040 TI - The molecular genetics of embryonic pattern formation in Drosophila. AB - Analysis of the genes that control the early events of Drosophila embryogenesis is providing details of the molecular processes underlying the positional specification of cells. There are two distinct phases: the first precedes the cellularization of the blastoderm embryo and is associated with a cascade of interactions between transcriptional regulators; the second occurs after cellularization and depends on communication between cells. These processes may be conserved in a wide range of invertebrates and vertebrates. PMID- 2901039 TI - Membrane guanylate cyclase is a cell-surface receptor with homology to protein kinases. AB - Guanylate cyclase has been strongly implicated as a cell-surface receptor on spermatozoa for a chemotactic peptide, and on various other cells as a receptor for atrial natriuretic peptides. Resact (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly Gly-Gly-Arg-Leu-NH2), the chemotactic peptide released by sea urchin Arbacia punctulata eggs, is specifically crosslinked to A. punctulata spermatozoan guanylate cyclase. After the binding of the peptide the state of guanylate cyclase phosphorylation modulates enzyme activity. We report here that the deduced amino-acid sequence of the spermatozoan membrane form of guanylate cyclase predicts an intrinsic membrane protein of 986 amino acids with an amino terminal signal sequence. A single transmembrane domain separates the protein into putative extracellular and cytoplasmic-catalytic domains. The cytoplasmic carboxyl-terminal 95 amino acids contain 20% serine, the likely regulatory sites for phosphorylation. Unexpectedly, the enzyme is homologous to the protein kinase family. PMID- 2901041 TI - Mosquito release blocked by fearful California residents. PMID- 2901042 TI - Calcitonin gene-related peptide acts as a novel vasodilator neurotransmitter in mesenteric resistance vessels of the rat. AB - Systemic blood pressure is controlled by changes in the resistance of the peripheral vascular bed for example in the mesenteric blood vessels. The tone of peripheral blood vessels is primarily maintained by sympathetic vasoconstrictor nerves. Although vasodilator innervation has been identified in certain isolated elastic arteries, it is not known whether vasodilator nerves contribute to the regulation of the peripheral resistance vessels. We present pharmacological evidence for the existence of nonadrenergic, noncholinergic (NANC) vasodilator nerves in the mesenteric resistance vessel of the rat and that the resistance is controlled by not only sympathetic vasoconstrictor nerves but also NANC vasodilator nerves. We also show that the neurogenic vasodilation was selectively abolished by depleting endogenous calcitonin gene-related peptide (CGRP), a potent vasodilator neuropeptide, from perivascular nerves. This indicates that CGRP is a novel vasodilator neurotransmitter and may play a role in control of the total peripheral resistance of systemic circulation through a local reflex mechanism. PMID- 2901043 TI - A mitotic inducer matures. PMID- 2901044 TI - Presynaptic regulation of the electrically evoked release of endogenous dopamine from the isolated neurointermediate lobe or isolated neural lobe of the rat pituitary gland in vitro. AB - Isolated neurointermediate lobes (NILs) or isolated neural lobes (NLs) of the rat pituitary gland were incubated in Krebs-HEPES solution which contained pargyline and the dopamine uptake inhibitor GBR 12921. The release of endogenous dopamine was determined by HPLC with electrochemical detection. Electrical stimulation of the pituitary stalk induced a frequency-dependent release of dopamine. The release of dopamine from the combined NIL evoked by stimulation at 15 Hz was increased by 130% in the presence of the dopamine D2 receptor antagonist, (-) sulpiride; the (+)-enantiomer of sulpiride had virtually no effect. When the stimulation frequency was 3 Hz (-)-sulpiride caused an increase in dopamine release by 230%. A similar increase was observed in the presence of domperidone, another dopamine D2 receptor antagonist. The dopamine receptor agonists, apomorphine and quinpirole, had no significant effects on the evoked release of dopamine indicating that under the present incubation conditions endogenous dopamine may have been maximally activating the autoinhibition. However, in the presence of 1 mumol/l (-)-sulpiride, apomorphine as well as quinpirole reduced the evoked release of dopamine in a concentration-dependent manner. The dopamine D1 receptor selective antagonist, SCH 23390, had no effect on the evoked release of dopamine at a concentration of 1 mumol/l. Only at a concentration of 10 mumol/l did SCH 23390 cause a small increase in dopamine release; this effect was, however, abolished in the presence of 1 mumol/l (-)-sulpiride.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901045 TI - Alpha-adrenoceptor activation of nictitating membrane and iris in cats. AB - Intra-arterial administration of (+)- and (-)-isomers of adrenaline and noradrenaline produced dose-related contraction of the nictitating membrane (NM) and dilation of the pupil in anesthetized cats. The relative potencies were (-) adrenaline greater than (+)-adrenaline = (-)-noradrenaline greater than (+) noradrenaline. Observations of the effects of alpha-adrenoceptor antagonists on ( )-noradrenaline activation of these two effectors were made simultaneously. All of the alpha 1-adrenoceptor antagonists tested produced a dose-related blockade of the NM with the relative potencies being prazosin greater than WB-4101 greater than phentolamine greater than phenoxybenzamine. In contrast, the iris dilator was blocked by WB-4101 and phenoxybenzamine but was refractory to antagonism by doses of prazosin and phentolamine that reduced the (-)-noradrenaline evoked NM response by 75-80% in the same animals. The alpha 2-adrenoceptor antagonist, yohimbine, produced significant inhibition of the NM only at high dose (1 mg/kg) but even at this level had no effect on pupil diameter. These results suggest that activation of the NM by exogenous noradrenaline is due solely to stimulation of alpha 1-adrenoceptors. alpha 2-adrenoceptors do not seem to significantly contribute to noradrenaline induced activation of either the NM or iris dilator muscle in vivo. In contrast, the alpha-adrenoceptors on the iris dilator muscle that are stimulated by exogenous noradrenaline can not easily be classified pharmacologically as either alpha 1- or alpha 2-adrenoceptors. PMID- 2901047 TI - [Neuroleptics in anxiety, depression and poorly understood physical symptoms]. PMID- 2901046 TI - Precontraction-induced contractile response of isolated canine portal vein to alpha-2 adrenoceptor agonists. AB - The responses of isolated canine portal veins, in either transverse or longitudinal strip, to alpha-2 adrenoceptor agonists were examined. B-HT920, a selective alpha-2 adrenoceptor agonist, did not elicit an appreciable response in the transverse strips of the portal vein under resting tone (0.5 g/mm width). When the preparation was partially precontracted with phenylephrine, prostaglandin F2 alpha, KCl, Bay K 8644, acetylcholine, 5-hydroxytryptamine, histamine, or A23187, B-HT920 evoked concentration-dependent contractile responses (3 x 10(-9)-10(-6) M). Maximum contractions, which depended on the precontraction levels and the precontracting substances, ranged from 10-35% of those evoked by norepinephrine 10(-5) M. Similar precontraction-dependent contractile responses were obtained in the longitudinal strips. Concentration response curves of B-HT920 in the transverse strips precontracted with prostaglandin F2 alpha were shifted by yohimbine to the right, but not by prazosin. Schild analysis yielded a slope of unity and a pA2 of 8.79. Clonidine also showed a similar precontraction-dependent contractile response. The lower part of the concentration-response curve of clonidine was shifted by yohimbine. These results may be explained by the presence of postsynaptic alpha-2 adrenoceptors in canine portal vein, which mediate a contractile response under certain conditions. PMID- 2901048 TI - [Depression induced by salazosulfapyridine in cyclothymia and Crohn disease]. PMID- 2901049 TI - Energy metabolism in glutamatergic neurons, GABAergic neurons and astrocytes in primary cultures. AB - Several aspects of energy metabolism (glucose utilization, lactate production, 14CO2 production from labeled glucose, glutamate or pyruvate, oxygen consumption and contents of ATP and phosphocreatine) were measured in cerebellar granule cells (glutamatergic) in primary cultures and compared with corresponding data for cerebral cortical neurons (mainly GABA-ergic) and astrocytes. Cerebellar granule cells and astrocytes were metabolically more active than cerebral cortical neurons. Glutamate which is utilized as a major metabolic fuel as astrocytes and, to a lesser extent, in cerebral cortical neurons, was virtually not oxidized in cerebellar granule cells. PMID- 2901051 TI - The effect of fluorocitrate on transmitter amino acid release from rat striatal slices. AB - In order to study the role of glutamine from glial cells for the synthesis of transmitter amino acids, the effect of the gliotoxic-substance fluorocitrate on amino acid release from slices was investigated. In vivo treatment with 1 nmol fluorocitrate reduced the Ca2+ dependent K+ evoked release of endogenous glutamate and GABA from the slices, whereas the glutamine efflux decreased and alanine efflux increased. The K+ evoked release of [3H]D-aspartate increased during fluorocitrate treatment. The latter is consistent with an inhibited uptake of D-aspartate into glial cells. Incubation of striatal slices with fluorocitrate (0.1 mM) decreased the glutamine efflux and increased the alanine efflux. Similar to the in vivo condition, fluorocitrate increased the K+ evoked [3H]D-aspartate release, but the K+ evoked release of endogenous glutamate and GABA increased rather than decreased. The ratio between the K+ evoked release of exogenous D aspartate to endogenous glutamate increased in both cases. The results suggest an important role of glial cells in the synthesis and inactivation of transmitter amino acids. PMID- 2901050 TI - Peroxidative block of glucose utilization and survival in CNS neuronal cultures. AB - The search for neuronotrophic factors addressing CNS neurons requires CNS neuronal cell cultures to quantitate putative effects on neuronal survival. Investigation of neurons dissociated from several embryonic CNS tissues have shown that their short-term survival requires supplementation of the culture medium with either pyruvate or the enzyme catalase. Pyruvate can be replaced with alpha-ketoglutarate or oxaloacetate, or with amino acids capable to transaminate to these three metabolites in the presence of exogenous alpha-ketoacid acceptors. Experiments were designed to evaluate the ability of cultured CNS neurons to utilize glucose as their primary source. We show that: (1) catalase requires the availability of glucose in the medium in order to exert its neuronal maintenance effect, (2) in the absence of catalase, the cells are unable to metabolize glucose through the tricarboxylic acid cycle, (3) catalase restores the neuronal ability to utilize glucose for oxydative metabolism, and renders redundant the use of other sources such as glutamate conversion to alpha-ketoglutarate, (4) graded concentrations of glucose in the medium affect in parallel these metabolic activities and the viability of the cultured neurons, and (5) anti-oxidant agents other than catalase mimic the catalase effects. We conclude that dissociated embryonic CNS neurons suffer from a block in glucose utilization which results from an imbalance between free radical attack and cellular defenses to it and speculate on a more general involvement of peroxidation damage in the trophic requirements for neuronal survival. PMID- 2901053 TI - CSF somatostatin is elevated in patients with postzoster neuralgia. AB - We evaluated the concentration of the neuropeptide somatostatin (SOM) in the CSF of patients with several neurologic diseases. Since SOM is localized in high concentrations in primary sensory pathways, such as the dorsal root ganglia and dorsal horn of the spinal cord, it might be involved in conditions of chronic pain due to functional alterations of nociceptive neurons, such as postinfectious zoster neuralgia. Our study indicated a marked elevation of SOM in patients suffering from postzoster neuralgia compared with controls. Comparison with other neurologic diseases revealed decreased CSF SOM levels in Parkinson's and Alzheimer's disease, unchanged values in patients with amyotrophic lateral sclerosis, and increased concentrations in patients with brain tumors. In neurodegenerative disorders, SOM levels in CSF seemed to reflect the anatomic distribution as well as a reduction or preservation of the peptide in certain brain areas affected by the disease process. In postzoster patients, postinfectious degeneration of dorsal root ganglia cells might cause deafferentation of dorsal horn neurons and activation of SOM-containing systems with increased release either locally from neurons in the dorsal horn of the spinal cord or from descending fiber projections. The results suggested that SOM may take part in the modulation of nociceptive responses. PMID- 2901052 TI - Time courses of amnesia development in two areas of the chick forebrain. AB - The roles of different forebrain structures in stages of memory formation were investigated by injecting agents into either the left medial hyperstriatum ventrale (MHV) or right lateral neostriatum (LNS) close to the time of one-trial taste-avoidance training. With L-glutamate injected into either the left MHV or right LNS 5 minutes pretraining, retention was good 1 minute posttraining but significantly impaired at 5 minutes and each subsequent time point. With emetine injected into either area, retention was still good 60 minutes posttraining but significantly impaired at 90 minutes. With ouabain, retention declined more slowly following injection into the right LNS (at 45 minutes) compared to injection in the left MHV (at 30 minutes). A second experiment confirmed the regional difference in amnesia development produced by ouabain. These results indicate that the duration of short-term memory is longer following inhibition of intermediate-term memory (ITM) in the right LNS, compared to inhibition of ITM in the left MHV. PMID- 2901054 TI - [Clotiazepam vs flunitrazepam in premedication in a day hospital regimen]. PMID- 2901056 TI - Changes in glutamate-evoked currents of frog motoneurones by extracellular Mg2+. AB - Responses of frog motoneurones to glutamate were studied using a single electrode voltage clamp method. At resting membrane potential glutamate evoked biphasic effects: firstly a transient outward current with reversal potential between -90 and -100 mV. Secondly an inward current with reversal potential near 0 mV and non linearly related to the holding potential. Mg2+ (1 mM) had no effect on the outward current but reduced the inward current and its slope conductance at holding potentials more negative than -60 mV. These data indicate that the operation of the inward current activated by glutamate was partly but not solely controlled by extracellular Mg2+. PMID- 2901055 TI - Catecholaminergic parasympathetic efferents within the dorsal motor nucleus of the vagus in the rat: a quantitative analysis. AB - Catecholaminergic vagal motor neurones were identified within the dorsal motor nucleus of the vagus, by retrograde tracing of True blue from the stomach followed by immunocytochemistry using antibodies directed against tyrosine hydroxylase. Presumed dopaminergic efferents were largely confined to caudal regions, where they averaged as much as 30% of the labelled efferents. Most but not all of these were also identified on the basis of acetylcholinesterase histochemistry. PMID- 2901057 TI - Formation of inositol trisphosphate by muscarinic agents does not stimulate transmitter release in cultured sympathetic neurons. PMID- 2901058 TI - Immunohistochemical evaluation of the neurotoxic effects of 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) on dopaminergic nigrostriatal neurons of young adult mice using dopamine and tyrosine hydroxylase antibodies. AB - The recovery of dopamine (DA) neurons in young adult mice from 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) damage was analyzed at various times after MPTP treatment with DA and tyrosine hydroxylase (TH) immunohistochemistry and also by chemical DA assay. A remarkable discrepancy in the recovery rate of DA and TH reactivities of the nigral neurons was observed: the TH immunoreactivities of both cell bodies in the substantia nigra and terminals in the neostriatum were markedly reduced 4 days after MPTP. However, these reactivities progressively improved and almost fully recovered after 25 days, while the DA immunoreactivities were maximally depleted 10 days after, and the depletion continued even through the 25th day. The alteration of DA levels was correlated with that of DA immunoreactivity. These findings suggest that a major effect of MPTP on the DA neurons of young adult mice is a transient neurotoxicity, and that the TH content improves more promptly than that of DA. PMID- 2901059 TI - Intracerebral dopaminergic transplants are not activated by electrical footshock stress activating in situ mesocorticolimbic neurons. AB - Male rats received a dopaminergic implant aimed either at the nucleus accumbens or the ventral tegmental area (VTA) following 6-hydroxydopamine lesion of their mesocorticolimbic dopaminergic system. Exposure to electrical footshock stress 6 months later markedly activated the mesocorticolimbic neurons in control animals as shown by the increase of dihydroxyphenylacetic acid (DOPAC) levels both in the nucleus accumbens and the VTA. However, no stress-induced activation was seen for the grafted neurons, irrespective of the area of implantation. These results indicate the lack of reinnervation and modulation of the grafted dopaminergic neurons by one of the important afferent systems regulating the activity of endogenous mesencephalic dopaminergic neurons. PMID- 2901060 TI - Codeine and homebake. PMID- 2901061 TI - Sulphasalazine and inflammatory bowel disease. PMID- 2901062 TI - Beta-adrenergic receptor antagonism in myopia. AB - A previous study has demonstrated that timolol maleate (0.5%), a non-selective beta-adrenergic antagonist, produces in emmetropes a significant reduction in accommodative convergence (AC) during the initial four minutes of a near-vision task. The present study has examined the effect of timolol on AC for three refractive groups (each comprising N = 20): emmetropes, early-onset myopes (EOMs), i.e. myopia onset prior to 15 years of age and late-onset myopes (LOMs), i.e. myopia onset after 15 years. A double-blind protocol was adopted between timolol and a saline control. AC was derived from accommodation stimuli of 3.3, 4.1 and 4.8 D with changes in heterophoria being assessed using a Maddox rod and tangent scale. The relationship between the ocular hypotensive effect of timolol and anterior corneal curvature was also investigated using a Goldmann applanation tonometer and a two-position keratometer (Haag-Streit). Timolol produced a significant reduction in AC in emmetropes but did not induce significant changes in AC in LOMs or EOMs. The timolol-induced reduction in IOP did not result in any changes in anterior corneal curvature. PMID- 2901063 TI - Epidural analgesia in the orthopaedic patient (continuing education credit). PMID- 2901064 TI - Nucleotide sequence of rat glutamine synthetase mRNA. PMID- 2901065 TI - A polymorphic DNA clone which maps to 19p13.2----19q12 (D19S27). PMID- 2901066 TI - A chromosome 1 BglI RFLP for the LR67 anonymous DNA segment [D1S26]. PMID- 2901067 TI - BglII polymorphism of the epidermal growth factor receptor (EGF-R) gene. PMID- 2901068 TI - A polymorphism of the beta 1 adrenergic receptor gene (BADR) detected with Bgl I. PMID- 2901069 TI - A retinoic acid receptor cDNA probe (RAR2) identifies a moderately frequent RFLP on chromosome 17. PMID- 2901070 TI - A cDNA probe (PheA12) from the hc-(ERBA) gene on chromosome 3 detects a high frequency RFLP. PMID- 2901071 TI - BanII and ScaI RFLPs at the human p53 gene locus. PMID- 2901073 TI - A new TaqI BO variant detected with the p49 probe on the human Y chromosome. PMID- 2901072 TI - Taq I RFLP in the human cellular retinol-binding protein (CRBP) gene. PMID- 2901074 TI - Human tyrosine hydroxylase (TH) genomic fragment (pHGTH4) identifies a PstI polymorphism. PMID- 2901076 TI - [Effect of somatostatin on phenazone pharmacokinetics in healthy men]. PMID- 2901075 TI - [Value of determining gamma-glutamyltransferase, alkaline phosphatase and aspartate and alanine aminotransferase activities in the evaluation of liver damage in alcoholics]. PMID- 2901078 TI - Peptide neurotransmitters--redundant vestiges? PMID- 2901077 TI - Transdermal scopolamine-induced psychosis. AB - Transdermal scopolamine (Transderm-Scop) is being increasingly used for effective prophylaxis of motion sickness. It is reported to have a lower incidence of CNS side effects than orally administered scopolamine. Although uncommon, such side effects occur more often in the elderly, in those with preexisting psychiatric disease, and in patients concurrently taking other medications with anticholinergic activity. Correct diagnosis may be delayed by the occult location of the delivery system, delayed onset of symptoms, prolonged action, absence of peripheral manifestations, and negative toxicologic screening tests. Treatment is usually supportive. Physostigmine should be reserved for the treatment of severe symptoms. PMID- 2901079 TI - Trophozoite and nuclear size, DNA base composition, and nucleotide sequence homology of several Entamoeba strains in axenic culture. AB - We carried out a comparative study of nuclear and trophozoite diameters and of DNA thermal denaturation in eight Entamoeba strains cultured axenically (four of them E. histolytica, two initially designated as E. invadens, one E. moshkovskii, and one E. histolytica-like), as well as an analysis of the overall DNA sequence homology of the non-E. histolytica strains. The average nuclear (N) and trophozoite (T) diameters (in micron) were, respectively: global averages +/- SD for E. histolytica strains, 6.5 +/- 2.5 and 28.8 +/- 3.7; E. invadens IP101, 5.8 and 27.5, and PZ, 7.8 and 33.6; E. moshkovskii FIC, 4.1 and 12.9; E. histolytica like Laredo strain, 5.0 and 20.6. The GC content of DNA, estimated by thermal elution in hydroxyapatite, was around 23% in HK9 and its clone HK9-1 and around 27% in the HM2 and HM3 E. histolytica strains; it was 37% in the Laredo strain, 26% in IP101, 35% in PZ, and 33% in FIC. The reassociation kinetics of PZ strain DNA showed that it consists of 40% repeated sequences and 60% unique sequences. By means of DNA association experiments in which one of each pair of DNAs tested had been labeled in vitro with 125I, we found the following overall sequence homology among the strains tested: PZ-FIC, 38%; IP101-Laredo, 38%; IP101-FIC, 47%; PZ-Laredo, 49%; Laredo-FIC, 69%; and IP101-PZ, 83%. We conclude that trophozoites of different E. histolytica strains have similar nuclear size and GC content, whereas these parameters and the nucleotide sequences are clearly different in every other Entamoeba species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901080 TI - Long-term treatment of anxiety: benefits and drawbacks. AB - Anxiety disorders are common conditions, often chronic, occurring in the general population with a prevalence of about 3%. Long-term use of tranquilizers varies from 0.5% of the total adult population in Sweden and 1.3% in Denmark to 3.1% in Great Britain and 5% in France. This use is tending to become more and more long term. Long-term efficacy of benzodiazepine medication has not been established. Adverse effects include psychomotor and cognitive impairment, especially in the elderly; some, but not all, effects show tolerance. Some impairment can be demonstrated even after years of use. Rebound and withdrawal reactions after long term use are common. Practical guidelines to minimize long-term use are suggested. PMID- 2901081 TI - Future directions in anxiety research. AB - More than 3.5 million patients suffer from anxiety in the United States of America alone. While our knowledge of the basic biological mechanisms of anxiety is very poor, we have a good understanding of the mechanism of action of various anxiolytic drugs at the molecular level. Their mechanism of action often relates to the inhibitory neurotransmitter GABA and it might be speculated that GABA has a role in anxiety. Future research will concentrate on designing better anxiolytic drugs, based for example on the discovery of partial benzodiazepine receptor agonists, and also on GABA uptake inhibitors as enhancers of GABAergic function. Furthermore, scientific studies will focus on a search for putative biological defects related to anxiety, such as defects in the GABA/benzodiazepine receptor chloride channel complex. PMID- 2901082 TI - Pharmacokinetics of neuroleptic drugs and the utility of plasma level monitoring. AB - Variability in response to antipsychotic drug treatment may be caused by variable patient compliance, interactions with other drugs, pharmacokinetic variations and variations in concentration-response relationships at the receptor level. Pharmacokinetic variations may in some cases be compensated by individual dosage adjustments based on plasma drug level measurements. The interpatient variability in response to a certain time-course of drug concentrations at the receptor site could hitherto only be assessed by clinical judgement. New methods for in vivo assessment of receptor occupancy hold promise for possible measurement of parameters accounting for at least part of the interindividual variation in drug response at the receptor level. Monitoring of fluphenazine, perphenazine, thiothixene and sulpiride plasma levels by specific chemical assay methods seems to offer some guidance to individualization of drug doses. Definite therapeutic plasma level ranges have not been established for chlorpromazine and haloperidol. However, monitoring plasma levels of chlorpromazine or haloperidol might be of value when drug-induced toxicity is suspected, and as a means of controlling patient compliance. PMID- 2901083 TI - Neuroleptic drugs in the treatment of acute psychosis: how much do we really know? AB - The efficacy of neuroleptic antipsychotic drugs has been well demonstrated and neuroleptics are the standard treatment of acute psychosis. However, important aspects of neuroleptic treatment, including course of response, optimal doses, and mechanism of action, remain poorly studied or controversial. Placebo controlled studies of the onset of the response of acute psychosis to neuroleptics are few and yield conflicting results. Studies of the relationship of doses and blood levels to the therapeutic effects of neuroleptics suggest that the optimal range of doses and levels is narrow and that commonly used doses are too high. Finally, studies of the mechanism of action of neuroleptics suggest that the dopamine hypothesis is based on unsupported assumptions concerning drug effects, drug distribution, and effective doses of drug. Alternative hypotheses, that the antipsychotic effects of the neuroleptics are mediated, at least in part, through alpha 1-adrenergic or serotonin 5-HT2 receptor antagonism, are reviewed. The evidence regarding these issues and controversies is discussed, and specific approaches to increase our understanding and enhance our use of the neuroleptics are suggested. PMID- 2901084 TI - Observations on the use of depot neuroleptics in schizophrenia. AB - This paper reviews some of the advantages and disadvantages of long-term maintenance therapy with neuroleptics in schizophrenia. The need to separate first-illness schizophrenia from chronic schizophrenia is illustrated. The reduction in the risk of a further acute relapse with continued medication and the likely duration of maintenance therapy are discussed. The true meaning of a further relapse to the patient in terms of reduced social and work function is also discussed. The advantages of using long-acting depot injections for drug administration are stressed. The complex issue of the correct dosage for maintenance is reviewed, with no proven advantage for either very high doses or very low doses. The frequency of depressive symptoms in schizophrenia is reviewed and the possible aetiologies discussed. The decision to use short- or long-term drug therapy, and whether to use a particular method of drug administration (oral or long-acting depot injections) should be separate issues. Depot injections may, on occasions, be the appropriate method of drug administration for short-term therapies, just as oral drugs have a place in the longer-duration maintenance treatments. PMID- 2901085 TI - Neuroleptic side effects: acute extrapyramidal syndromes and tardive dyskinesia. AB - The neuroleptic-induced motor system side effects of acute extrapyramidal syndromes (EPS) and tardive dyskinesia (TD) are the major limitations of these drugs. Effective strategies for managing these problems are based on the clinical presentations, pathophysiological processes, and a complex interaction of patient and treatment variables. New concepts about the causes and long-term outcome of acute EPS and TD are emerging to challenge some of the commonly held views about these syndromes. The primary method of preventing undue side effects is to use the lowest effective dose of both neuroleptic and anti-EPS drugs. The pressing need is for novel compounds which treat schizophrenia and are free of the undesirable motor system effects (a nonneuroleptic neuroleptic). PMID- 2901086 TI - Future treatment of schizophrenia. AB - In spite of 35 years of experience with antipsychotic drugs, the psychiatrists are still faced with the limitations of these drugs: no or minimal therapeutic effect in hallucinations and delusions in about 25% of schizophrenic patients; persisting anergia and emotional withdrawal in otherwise successfully treated patients; a great spectrum of side effects, some irreversible. Quo vadis? An incidental discovery of a completely new drug, a new "chlorpromazine" would be the ideal solution, but for the present, one has to continue with the small pragmatic steps, especially within the following areas: (a) the selective antidopaminergic drugs, especially the substituted benzamides, may be further developed in the direction of antipsychotic selectivity with fewer and fewer extrapyramidal side effects; (b) the atypical clozapine ought soon to have successors, hopefully without the risk of bone marrow depression and cardiovascular side effects; (c) the D1 antagonists as well as the D1 agonists may imply therapeutically valuable effects; (d) the dopamine autoreceptor has long been in focus, but until now, no pure agonist has been found, and the drugs available, including (-)3-PPP, appear to have many side effects; (e) serotonin antagonists may be an interesting possibility; and (f) when it may be possible to influence brain peptides more efficiently than up to now, this area will probably provide us with several psychotropic drugs. Furthermore, during the search for new antipsychotic drugs, one must not forget to improve the practical use of available neuroleptics and of nonpharmacological, psychosocial treatment modalities. PMID- 2901087 TI - p21ras-induced responsiveness of phosphatidylinositol turnover to bradykinin is a receptor number effect. AB - Proteins encoded by ras genes have recently been reported to couple certain growth factor receptors to phospholipase C, the enzyme catalyzing phosphatidylinositol breakdown. To investigate this hypothesis, the normal and the transforming Ha-, Ki-, and N-ras genes were each transfected into Rat-1 fibroblasts under the control of strong promoters. Several cell lines, both normal and transformed, were selected that expressed high levels of p21ras. Phosphatidylinositol turnover was measured in these cells in response to a wide variety of peptide factors; bradykinin was found to have a greatly enhanced effect on the p21ras overexpressors relative to the parental and control cells. Bradykinin receptor numbers were measured in these lines and found to be up to 40 fold higher in the p21ras overexpressors than in the parental cells. This was found to be the case for both normal and transforming forms of all three varieties of ras genes. Receptor number correlated well with the bradykinin dependent phosphatidylinositol turnover response in all cases. These data indicate that the effects of p21ras on cellular responses to the peptide hormone bradykinin are due to changes in receptor number rather than to direct coupling by p21ras between the receptor and phospholipase C. PMID- 2901088 TI - Structure of the coding sequence and primary amino acid sequence of acetyl coenzyme A carboxylase. AB - Acetyl-coenzyme A carboxylase (Ac-CoA carboxylase; EC 6.4.1.2) catalyzes the rate limiting reaction in long-chain fatty acid biosynthesis. To investigate the mechanism of genetic control of expression of Ac-CoA carboxylase and the relationship between its structure and function, cDNA clones for Ac-CoA carboxylase were isolated. The complete coding sequence contains 7035 bases; it encodes a polypeptide chain of 2345 amino acids having a Mr of 265,220. The sequences of several CNBr peptides of Ac-CoA carboxylase were localized within the predicted protein sequence as were those peptides that contain the sites for phosphorylation. The deduced protein contains one putative site for biotinylation in the NH2-terminal half. The "conserved" biotinylation site peptide, Met-Lys Met, is preceded by valine, whereas alanine is found in a similar position in all other known biotin-containing proteins. The primary sequences of Ac-CoA carboxylase and carbamoyl phosphate synthetase exhibit substantial identity. PMID- 2901089 TI - Cloning, nucleotide sequence, and potential regulatory elements of the glutamine synthetase gene from murine 3T3-L1 adipocytes. AB - Glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming); EC 6.3.1.2] specific activity, cellular content, mRNA abundance, and gene transcription rate increase by greater than 100-fold during adipocyte differentiation of 3T3-L1 cells. In 3T3-L1 adipocytes dexamethasone increases, whereas insulin as well as N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate decrease, glutamine synthetase gene expression. We analyzed the nucleotide sequence of a 1.9-kilobase Sal I-EcoRI restriction fragment from a 3T3-L1 glutamine synthetase genomic clone. This genomic fragment is composed of 1851 base pairs (bp) and includes the first exon and 1029 bp of the 5' flanking sequence. The 600 bp at the 3' end of the 1.9-kb Sal I-EcoRI restriction fragment constitute an open reading frame. We identified the transcription start site at a location 222 bp upstream of the glutamine synthetase coding sequences. The 5' flanking region of the gene encompasses several potential regulatory elements including TATA and CAAT sequences and a 40-bp poly(dT-dG).poly(dC-dA) putative enhancer element. Potential hormone and fat-specific regulatory elements are also located upstream of the transcription start site; they include glucocorticoid and cAMP response elements and fat-specific elements. These potential regulatory elements could account for the differentiation-associated changes and hormone-mediated changes seen in glutamine synthetase gene transcription and mRNA abundance. PMID- 2901090 TI - Alternative splicing generates messages encoding rat c-erbA proteins that do not bind thyroid hormone. AB - The nucleotide and predicted amino acid sequences of two variant cDNAs [rat brain thyroid hormone receptor (rTR alpha) vI and vII], isolated from a rat brain cDNA library by using the Pst I fragment of v-erbA, showed virtual identity with the rat brain thyroid hormone receptor (rTR alpha) [Thompson, C. C., Weinberger, C., Lebo, R. & Evans, R. M. (1987) Science 237, 1610-1614] in the putative DNA binding domain and in the first 180 amino acids of the hormone binding domain but no similarity except for 5 amino acids at the extreme 3' end. Isolation and sequencing of the 3' end of the gene coding for rTR alpha, vI and vII mRNAs revealed that the 3' heterogeneity is due to alternative splicing of the primary transcripts of the same gene. RNA transfer blot analyses with probes unique to rTR alpha, rTR alpha vI, and rTR alpha vII showed that only the variant mRNAs are abundantly expressed in rat brain, contrary to the previously reported high-level expression of rTR alpha. Since in vitro translation products of rTR alpha vI and rTR alpha vII did not bind thyroid hormones specifically, our findings explain the discrepancy between the reported abundance of the receptor mRNA and the low receptor levels determined by ligand binding studies in rat brain. These variant mRNAs are also expressed in kidney, heart, spleen, and liver, albeit at lower levels. The presence of an intact DNA binding domain in rTR alpha vI and rTR alpha vII suggests that the variants might have modulating functions in thyroid hormone action. PMID- 2901091 TI - Characterization of the gene for the a subunit of human factor XIII (plasma transglutaminase), a blood coagulation factor. AB - Factor XIII (plasma transglutaminase, fibrin stabilizing factor) is a glycoprotein that circulates in blood as a tetramer (a2b2) consisting of two a and two b subunits. The primary structures of the a and b subunits of human factor XIII have been reported by a combination of cDNA cloning and amino acid sequence analysis. To establish the gene structure of the a subunit for factor XIII, several human genomic libraries were screened by using the cDNA encoding the a subunit as a probe. Among approximately equal to 5 x 10(7) recombinant phage, 121 have been shown to contain an insert encoding a portion of the a subunit. Twenty-five unique clones were then characterized by restriction mapping, Southern blotting, and DNA sequencing. Overlapping clones encoding the a subunit of factor XIII span greater than 160 kilobases. The gene was found to contain 15 exons separated by 14 introns. All the sequences of the introns at the intron-exon boundaries were GT-AG, which are the same as those found in other eukaryotic genes. DNA sequence analysis revealed that the activation peptide released by thrombin, the active site cysteine region, the two putative calcium binding regions, and the thrombin cleavage site leading to inactivation are encoded by separate exons. This suggests that the introns may separate the a subunit into functional and structural domains. A comparison of the amino acid sequence deduced from the genomic DNA sequence with those deduced from cDNA or determined by amino acid sequence analysis of the plasma and placental proteins revealed apparent amino acid polymorphisms in six positions of the polypeptide chain of the a subunit. PMID- 2901092 TI - Specific dephosphorylation of phosphoproteins by protein-serine and -tyrosine kinases. AB - Five protein kinases are shown to serve as specific phosphatases in the absence of ADP. Although the rates of hydrolysis are very slow compared to the forward phosphorylation rates under optimal conditions, they are of the same order as the reverse reaction in the presence of ADP. Because cells contain approximately equal to 3 mM ATP, neither the reverse reaction nor the phosphatase is likely to play a physiological role. beta-casein B phosphorylated by the catalytic subunit of cAMP-dependent protein kinase (protein kinase A) is specifically dephosphorylated by protein kinase A but not by polypeptide-dependent protein kinase (protein kinase P). beta-casein B phosphorylated by protein kinase P is specifically dephosphorylated by protein kinase P but not by protein kinase A. Histone H1 phosphorylated by protein kinase C is dephosphorylated by the same enzyme in the absence of ADP. In all cases tested addition of ADP and F1-ATPase accelerates moderately the rate of dephosphorylation. Native H+-ATPase from yeast plasma membranes is isolated mainly in the phosphorylated form. It is dephosphorylated and rephosphorylated by protein kinase P but not by protein kinase A. Protein-tyrosine kinase of the epidermal growth factor receptor phosphorylates the random synthetic polypeptide poly(Glu80Tyr20). The phosphorylated polymer is specifically dephosphorylated in the absence of ADP by epidermal growth factor receptor preparations but not by insulin receptor preparations. The same polymer phosphorylated by insulin receptor is dephosphorylated by insulin receptor but not by epidermal growth factor receptor preparations. By using a cycle of dephosphorylation-rephosphorylation, it is possible to identify proteins that are phosphorylated by these protein kinases in vivo. Should this method be applicable to additional protein kinases, it should be possible to estimate the quantitative contribution of each protein kinase to a single phosphoprotein. PMID- 2901093 TI - Parathyroid hormone modulates transforming growth factor beta activity and binding in osteoblast-enriched cell cultures from fetal rat parietal bone. AB - Transforming growth factor beta (TGF-beta) is produced by bone cells, is abundant in bone matrix, and regulates bone cell biochemical processes. In osteoblast enriched fetal rat parietal bone cell cultures, low TGF-beta doses increase DNA synthesis, whereas higher levels are less mitogenic, stimulate collagen production, and decrease alkaline phosphatase activity. Parathyroid hormone by itself has minimal effects on these processes, but it opposes the effects of TGF beta and alters TGF-beta binding to its receptors in osteoblast-enriched cultures. Some functions ascribed to parathyroid hormone in bone may therefore result from alterations in TGF-beta activity, suggesting that the local effects of TGF-beta in bone are under systemic hormonal control. PMID- 2901094 TI - Cell contacts are required for induction by cortisol of glutamine synthetase gene transcription in the retina. AB - In embryonic neural retina the enzyme glutamine synthetase [GS; L glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] is a glia-specific differentiation marker inducible with cortisol. We show that cortisol elicits GS mRNA accumulation by stimulating transcription of the GS gene and that this stimulation requires cell contacts: in dissociated and separated retina cells GS gene transcription was not induced; when the separated cells were reassembled into multicellular aggregates, restoring cell contacts, accumulation of GS mRNA was again inducible. In cells dissociated from retina tissue that had been preinduced with cortisol, GS gene transcription rapidly declined, despite continued hormone availability. In the separated cells transcription of the histone H3.3 gene and accumulation of carbonic anhydrase II mRNA were unaffected; therefore, cell separation selectively precluded induction of the GS gene. These findings provide direct evidence for the regulatory role of cell contacts in hormonal control of gene transcription. PMID- 2901095 TI - Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17. AB - Mouse trisomy 16 has been proposed as an animal model of Down syndrome (DS), since this chromosome contains homologues of several loci from the q22 band of human chromosome 21. The recent mapping of the defect causing familial Alzheimer disease (FAD) and the locus encoding the Alzheimer amyloid beta precursor protein (APP) to human chromosome 21 has prompted a more detailed examination of the extent of conservation of this linkage group between the two species. Using anonymous DNA probes and cloned genes from human chromosome 21 in a combination of recombinant inbred and interspecific mouse backcross analyses, we have established that the linkage group shared by mouse chromosome 16 includes not only the critical DS region of human chromosome 21 but also the APP gene and FAD linked markers. Extending from the anonymous DNA locus D21S52 to ETS2, the linkage map of six loci spans 39% recombination in man but only 6.4% recombination in the mouse. A break in synteny occurs distal to ETS2, with the homologue of the human marker D21S56 mapping to mouse chromosome 17. Conservation of the linkage relationships of markers in the FAD region suggests that the murine homologue of the FAD locus probably maps to chromosome 16 and that detailed comparison of the corresponding region in both species could facilitate identification of the primary defect in this disorder. The break in synteny between the terminal portion of human chromosome 21 and mouse chromosome 16 indicates, however, that mouse trisomy 16 may not represent a complete model of DS. PMID- 2901096 TI - Interleukin 4 induces membrane Thy-1 expression on normal murine B cells. AB - Thy-1, a cell-surface glycoprotein of undetermined function, is expressed in relatively large amounts on mouse thymocytes, peripheral T cells, and neurons. It is widely used as a marker to distinguish peripheral T cells from B cells in mice. We show here that, in five distinct mouse strains, recombinant interleukin 4 (IL-4/B-cell stimulatory factor 1) strikingly induces membrane expression of Thy-1 on the vast majority of lipopolysaccharide (LPS)-stimulated normal murine B cells. Thy-1+ B cells are precursors for immunoglobulin-secreting cells. RNA blot analysis indicates that B cells express a Thy-1 mRNA of 1.8 kilobases, the same size as that found in T cells. Cell mixing experiments show that only cells derived from Thy-1.2+ donors express Thy-1.2, indicating that B cells expressing Thy-1 have not passively absorbed the glycoprotein from another cell source. Recombinant interferon-gamma inhibits Thy-1 induction by B cells stimulated with LPS and IL-4. Thy-1 is also induced on B cells that have been stimulated as a result of the specific activation of an IL-4-producing T-helper clone. Anti-IL-4 monoclonal antibody inhibits the induction of B-cell Thy-1 in this T-cell-B-cell interaction. PMID- 2901098 TI - Chromosome jumping from D4S10 (G8) toward the Huntington disease gene. AB - The gene for Huntington disease (HD) has been localized to the distal portion of the short arm of human chromosome 4 by linkage analysis. Currently, the two closest DNA markers are D4S10 (G8), located approximately equal to 3 centimorgans centromeric to HD, and D4S43 (C4H), positioned 0-1.5 centimorgans from HD. In an effort to move closer to the HD gene, with the eventual goal of identifying the gene itself, we have applied the technique of chromosome jumping to this region. A 200-kilobase jumping library has been constructed, and a jump from D4S10 has been obtained and its approximate distance verified by pulsed field gel electrophoresis. Two restriction fragment length polymorphisms have been identified at the jump locus, which is denoted D4S81. Linkage analysis of previously identified recombinants between D4S10 and HD or D4S10 and D4S43 shows that in two of five events the jump has crossed the recombination points. This unequivocally orients D4S10 and D4S81 on the chromosome, provides additional markers for HD, and suggests that recombination frequency in this region of chromosome 4 may be increased, so that the physical distance from D4S10 to HD may not be as large as originally suspected. PMID- 2901097 TI - Interleukin 1 amplifies receptor-mediated activation of phospholipase A2 in 3T3 fibroblasts. AB - Human recombinant interleukin 1 alpha (IL-1 alpha) and IL-1 beta stimulated prostaglandin E2 synthesis in 3T3 fibroblasts in a time- and concentration dependent manner. Enhanced prostaglandin E2 synthesis after IL-1 treatment was apparent by 1 hr and continued to increase for at least 2 days. Half-maximal stimulation occurred at 0.5 pM IL-1 alpha or IL-1 beta, and both interleukins were equally effective, with maximal stimulation occurring in response to 5-10 pM IL-1. In contrast to IL-1, bradykinin stimulation of prostaglandin E2 synthesis is rapid; its effect is maximal by 5 min. In cells that had been pretreated with IL-1 for 24 hr, prostaglandin E2 synthesis in response to bradykinin was amplified more than 10-fold. IL-1 also amplified the receptor-mediated formation of prostaglandin E2 by bombesin and thrombin. The lymphokine did not affect bradykinin receptor number or affinity. IL-1 treatment induced phospholipase A2 and cyclooxygenase but not phospholipase C or prostaglandin E isomerase. It also enhanced bradykinin-stimulated GTPase activity, suggesting possible induction of the GTP-binding regulatory protein coupled to the bradykinin receptor. Thus, IL-1 enhanced receptor-mediated release of prostaglandin E2 in response to bradykinin, bombesin, and thrombin by increasing the cellular levels of phospholipase A2, cyclooxygenase, and GTP-binding regulatory protein(s). PMID- 2901099 TI - HLA-DQ rather than HLA-DR region might be involved in dominant nonsusceptibility to diabetes. AB - Since HLA-DRw15 (a subdivision of the HLA-DR2 specificity previously called DR2 long) is associated with dominant nonsusceptibility to insulin-dependent diabetes mellitus (IDDM), while HLA-DRw16 (another subdivision of HLA-DR2, previously called DR2 short) is positively associated with the disease, we looked for particular characteristics of HLA products encoded by the DR2 haplotypes of IDDM patients. The results show the following: (i) HLA-DQ molecules of HLA-DRw15 positive IDDM patients are different from those of HLA-DRw15-positive controls, suggesting that the HLA-DQ gene of DRw15 haplotypes is involved in a protective effect. (ii) HLA-DR and -DQ products of DRw16-positive IDDM are functionally indistinguishable from those of HLA-DRw16-positive controls. Furthermore, our data provide evidence that the residue at position 57 on the DQ beta chain could play a crucial biological role in antigen presentation to T cells as far as the DRw16 haplotype is concerned. This observation fits with the recent observation of correlation between DQ beta allelic polymorphism at position 57 and both susceptibility and resistance to IDDM. PMID- 2901100 TI - Induction of erythroid differentiation and modulation of gene expression by tiazofurin in K-562 leukemia cells. AB - Tiazofurin (2-beta-D-ribofuranosyl-4-thiazole-carboxamide; NSC 286193), an antitumor carbon-linked nucleoside that inhibits IMP dehydrogenase (IMP:NAD+ oxidoreductase; EC 1.1.1.205) and depletes guanylate levels, can activate the erythroid differentiation program of K-562 human leukemia cells. Tiazofurin mediated cell differentiation is a multistep process. The inducer initiates early (less than 6 hr) metabolic changes that precede commitment to differentiation; among these early changes are decreases in IMP dehydrogenase activity and in GTP concentration, as well as alterations in the expression of certain protooncogenes (c-Ki-ras). K-562 cells do express commitment-i.e., cells exhibit differentiation without tiazofurin. Guanosine was effective in preventing the action of tiazofurin, thus providing evidence that the guanine nucleotides are critically involved in tiazofurin-initiated differentiation. Activation of transcription of the erythroid-specific gene that encodes A gamma-globin is a late (48 hr) but striking effect of tiazofurin. Down-regulation of the c-ras gene appears to be part of the complex process associated with tiazofurin-induced erythroid differentiation and relates to the perturbations of GTP metabolism. PMID- 2901101 TI - Central mammalian neurons normally resistant to glutamate toxicity are made sensitive by elevated extracellular Ca2+: toxicity is blocked by the N-methyl-D aspartate antagonist MK-801. AB - It is widely held that a glutamate-like toxin that resembles N-methyl-D-aspartate may be responsible for the death of nerve cells seen after severe neurological insults including stroke, seizures, and degenerative disorders, such as Huntington disease, Alzheimer disease, and the amyotrophic lateral sclerosis parkinsonism-dementia complex found on Guam. One puzzling fact about these maladies is the differential vulnerability of specific groups of neurons peculiar to each condition. We report here that an identified population of central neurons, rat retinal ganglion cells, are resistant to the neurotoxic effects of millimolar concentrations of glutamate under otherwise normal culture conditions. Patch-clamp experiments show that this resistance is associated with a very small ionic current response to N-methyl-D-aspartate. Varying the ionic milieu by increasing the extracellular Ca2+ concentration, however, results in a striking increase in glutamate-induced cell death in this population. Under these conditions, Mg2+ or the amino acid antagonist MK-801 [(+)-5-methyl-10,11-dihydro 5H-dibenzo-(alpha,gamma)-cyclohepten-5 ,10-imine maleate], blockers of N-methyl-D aspartate receptor-coupled ion channels, completely abrogate the lethal effects of glutamate. These findings strongly suggest that Ca2+ entry through N-methyl-D aspartate-activated channels is responsible for this type of neuronal death and suggest strategies that may be clinically useful in the treatment of various neurological disorders. PMID- 2901102 TI - The same substitution, glutamic acid----lysine at position 501, occurs in three alloalbumins of Asiatic origin: albumins Vancouver, Birmingham, and Adana. AB - A strategy is described for identifying structural changes in genetic variants of human serum albumin (alloalbumins). By use of this strategy we have determined an amino acid substitution in three alloalbumins of Asiatic origin. The same amino acid exchange, glutamic acid----lysine at position 501, occurs in albumins Vancouver and Birmingham, both from families that migrated from northern India, and also in albumin Adana from Turkey. This exchange corresponds to a single base mutation in the codon GAG to AAG and accords with the slow mobility of the three albumins at pH 8.6. Each of the three alloalbumins had been reported to be a new variant, yet they have the same substitution. These results emphasize the need for structural study of genetic variants that have been differentiated only by nonspecific physical criteria such as dye binding and electrophoretic mobility. We know of no other description of the substitution involved in an alloalbumin originating from the Indian subcontinent. However, the same change of glutamic acid----lysine at position 501 may be present in several other named variants reported for populations in north India and the surrounding regions. PMID- 2901103 TI - Acetyladenylate plays a role in controlling the direction of flagellar rotation. AB - Cells of Escherichia coli deleted for genes that code for the transducers and all the known cytoplasmic Che proteins except CheY responded reversibly to the addition of acetate by spinning their flagellar motors clockwise. By varying growth conditions and using metabolic inhibitors and mutants deficient in acetate metabolism, this effect was shown to require acetate-CoA synthetase [acetate:CoA ligase (AMP-forming); EC 6.2.1.1], an enzyme that catalyzes the formation of acetyl-CoA from acetate by an acetyladenylate intermediate. A mutant deficient in this enzyme but retaining the chemotaxis genes was deficient for chemotaxis. Thus, acetyladenylate appears to play a role in generating clockwise rotation at the level of CheY or the motor. PMID- 2901104 TI - Antibodies to synthetic peptides from the tubulin regulatory domain interact with tubulin and microtubules. AB - The carboxyl-terminal region of tubulin alpha and beta subunits plays a major role in regulating its assembly into microtubules and constitutes an essential domain for the selective interaction of microtubule-associated proteins (MAPs). With the goal of understanding the structural basis of the regulatory function of the carboxyl-terminal domains of tubulin subunits, we have produced rabbit antisera against two MAP-interacting peptides Lys-Asp-Tyr-Glu-Glu-Val-Gly-Val-Asp Ser-Val-Glu of alpha-tubulin and Tyr-Gln-Gln-Tyr-Gln-Asp-Ala-Thr-Ala-Asp-Glu-Gln Gly of beta subunit. The affinity-purified alpha and beta anti-peptide antibodies interacted specifically with tubulin and with the respective peptide antigens but did not interact with MAPs. Substoichiometric amounts of both antibodies showed the capacity to inhibit in vitro MAP-induced tubulin assembly and to promote a fast depolymerization of preassembled microtubules. Taxol-promoted assembly of pure tubulin was not inhibited by the antibodies. In the presence of MAP-2 and taxol, the antibodies decreased the MAP-2 content of taxol-promoted microtubules. The interaction with microtubules was corroborated by immunofluorescence experiments in HeLa and NE-18 lung carcinoma cells. The epitopes recognized by the alpha and beta anti-peptide antibodies appear to be located in the outer surface of the microtubular structure. PMID- 2901105 TI - Pharmacologically different Na/H antiporters on the apical and basolateral surfaces of cultured porcine kidney cells (LLC-PK1). AB - Proximal tubule cells of the kidney contain, on their apical surface, an amiloride-sensitive Na/H antiporter that functions in Na reabsorption and proton secretion. We have investigated the localization of the antiporter in a cloned cell line of porcine renal origin, LLC-PK1/Cl4, which is often considered to be a useful model of the proximal tubule. Transport measurements were performed with differentiated monolayers grown on Nuclepore filters, permitting independent access to the apical and basolateral cell surfaces. In control experiments with LLC-PK1/Cl4 monolayers, three marker transport systems showed the expected polarity: 87% of ouabain-sensitive Rb uptake was at the basolateral surface, and 99% of Na-dependent alpha-methylglucoside transport and 93% of Na-dependent D aspartate (L-glutamate) transport were at the apical surface. By contrast, the monolayers displayed significant Na/H antiporter activity (assayed as ethylisopropylamiloride-sensitive 22Na uptake) at both cell surfaces, with an apical uptake rate amounting to 44% and a basolateral rate amounting to 56% of the total. Significantly, the apical and basolateral antiporters could readily be distinguished from one another on the basis of ethylispropylamiloride sensitivity. The apical system had an IC50 of 13 microM, close to that reported for kidney brush border vesicle preparations, whereas the basolateral system had an IC50 of 44 nM, similar to values seen in undifferentiated LLC-PK1 cells and other cultured cell lines. The PKE20 mutant, previously selected from LLC-PK1/Cl4 on the basis of resistance to ethylisopropylamiloride, was found to overexpress the more resistant antiporter both during rapid growth and on its apical cell surface at confluence; normal amounts of the more sensitive antiporter were seen on the basolateral surface of confluent PKE20 cells. Taken together, these results suggest that there are two distinct forms of the Na/H antiporter, which are under separate genetic control. PMID- 2901106 TI - Detection of DNA "fingerprints" of cultivated rice by hybridization with a human minisatellite DNA probe. AB - A human minisatellite DNA probe detects several restriction fragment length polymorphisms in cultivars of Asian and African rice. Certain fragments appear to be inherited in a Mendelian fashion and may represent unlinked loci. The hybridization patterns appear to be cultivar-specific and largely unchanged after the regeneration of plants from tissue culture. The results suggest that these regions of the rice genome may be used to generate cultivar-specific DNA fingerprints. The demonstration of similarity between a human minisatellite sequence and polymorphic regions in the rice genome suggests that such regions also occur in the genomes of many other plant species. PMID- 2901107 TI - Restriction fragment length polymorphism linkage map for Arabidopsis thaliana. AB - We have constructed a restriction fragment length polymorphism linkage map for the nuclear genome of the flowering plant Arabidopsis thaliana. The map, containing 90 randomly distributed molecular markers, is physically very dense; greater than 50% of the genome is within 1.9 centimorgans, or approximately 270 kilobase pairs, of the mapped DNA fragments. The map was based on the meiotic segregation of markers in two different crosses. The restriction fragment length polymorphism linkage groups were integrated with the five classically mapped linkage groups by virtue of mapped mutations included in these crosses. Markers consist of both cloned Arabidopsis genes and random low-copy-number genomic DNA clones that are able to detect polymorphisms with the restriction enzymes EcoRI, Bgl II, and/or Xba I. These cloned markers can serve as starting points for chromosome walking, allowing for the isolation of Arabidopsis genes of known map location. The restriction fragment length polymorphism map also can associate clones of unknown gene function with mutant phenotypes, and vice versa. PMID- 2901108 TI - In vitro reinnervation of adult rat muscle fibres by foreign neurons and transformed chromaffin PC12 cells. AB - Adult rat muscle fibres were dissociated by using collagenase and maintained in culture. One to nine days later, neurons obtained from stages 22-30 Xenopus laevis embryos, or neonatal spinal cord, or pheochromocytoma (PC12) cells treated with nerve growth factor were added. Subsequently, the co-cultures were maintained for up to eight days. Functional synapses were formed with variable efficiency: 12% in rat-Xenopus nerve-muscle co-cultures, 23% in rat-rat and 33% in PC12 co-cultures. Miniature endplate potentials (MEPPs) and currents (MEPCs) were recorded, at frequencies ranging from 0.01 to 0.9 Hz. Their mean amplitude was smaller than in normal mammalian muscles. The rise time and time-constant of decay of MEPCs was about seven to ten times longer than that found in the original muscle, resembling immature synapses. (+)-Tubocurarine abolished the MEPPs in the rat-PC12 neuromuscular junctions. It is concluded that dissociated adult rat muscle fibres retain their ability of being reinnervated, and can form functional synapses with foreign neurons and transformed chromaffin cells. PMID- 2901109 TI - The reaction-limited kinetics of membrane-to-surface adhesion and detachment. AB - Biological adhesion is frequently mediated by specific membrane proteins (adhesion molecules). Starting with the notion of adhesion molecules, we present a simple model of the physics of membrane-to-surface attachment and detachment. This model consists of coupling the equations for deformation of an elastic membrane with equations for the chemical kinetics of the adhesion molecules. We propose a set of constitutive laws relating bond stress to bond strain and also relating the chemical rate constants of the adhesion molecules to bond strain. We derive an exact formula for the critical tension. We also describe a fast and accurate finite difference algorithm for generating numerical solutions of our model. Using this algorithm, we are able to compute the transient behaviour during the initial phases of adhesion and detachment as well as the steady-state geometry of adhesion and the velocity of the contact. An unexpected consequence of our model is the predicted occurrence of states in which adhesion cannot be reversed by application of tension. Such states occur only if the adhesion molecules have certain constitutive properties (catch-bonds). We discuss the rational for such catch-bonds and their possible biological significance. Finally, by analysis of numerical solutions, we derive an accurate and general expression for the steady-state velocity of attachment and detachment. As applications of the theory, we discuss data on the rolling velocity of granulocytes in post-capillary venules and data on lectin-mediated adhesion of red cells. PMID- 2901110 TI - Mechanism of synaptic inhibition by noradrenaline acting at alpha 2 adrenoceptors. AB - The actions of agonists at alpha 2-adrenoceptors were investigated on single cells of the submucous plexus of the guinea pig small intestine. Intracellular recordings were made from neurons in vitro, and noradrenaline and other agonists were applied by adding them to the superfusion solution. The actions of noradrenaline released from terminals of sympathetic nerves was also studied by stimulating the nerves and recording the inhibitory postsynaptic current; this current can be mimicked by brief applications of noradrenaline from a pipette tip positioned within 50 micron of the neuron. The alpha 2-adrenoceptor-bound noradrenaline with an apparent dissociation constant of 15 microM, determined by the method of partial irreversible receptor inactivation: clonidine and 5-bromo-6 (2-imidazolin-2-ylamino)-quinoxaline (UK 14304) had dissociation constants of 36 nM and 2.5 microM respectively. Noradrenaline and UK 14304 caused maximal hyperpolarizations, or outward currents; clonidine was a full agonist in only 4 of 35 cells, a partial agonist in 25 cells, and without effect in 4 cells. Clonidine acted as a competitive antagonist of noradrenaline in those cells in which it lacked agonist action; its dissociation equilibrium constant determined by Schild analysis was about 20 nM. The potassium conductance increased by the alpha 2-adrenoceptor agonists, whether they were applied exogenously or released by stimulation of presynaptic nerves, showed marked inward rectification. The neurons showed inward rectification also in the absence of agonist; both types of rectification were eliminated by rubidium (2 mM), barium (3-30 microM) and caesium (2 mM). When the recording electrodes contained the nonhydrolysable derivative of guanosine 5'-triphosphate (GTP), guanosine 5'-O-(3 thiotriphosphate, GTP-gamma-S), the effects of applied alpha 2-adrenoceptor agonists did not reverse when they were washed from the tissue, implying that GTP hydrolysis is necessary for the termination of agonist action. Pretreatment with pertussis toxin abolished the inhibitory synaptic potential (IPSP) and agonist induced hyperpolarizations. Phorbol 12,13-dibutyrate, forskolin, cholera toxin and sodium fluoride did not affect the responses to alpha 2-adrenoceptor agonists. The synaptic hyperpolarization resulting from sympathetic nerve stimulation, or the hyperpolarization evoked by a brief (3-5 ms) application of noradrenaline, began after a latency of about 30 and 60 ms respectively.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2901112 TI - 5-Hydroxytryptamine1A receptor-mediated effects of buspirone, gepirone and ipsapirone. AB - The effects of the nonbenzodiazepine anxiolytic agents, buspirone, gepirone and ipsapirone on body temperature and corticosterone secretion were studied in the rat. The administration of buspirone, gepirone and ipsapirone resulted in dose related decreases in body temperature and increases in the plasma concentration of corticosterone. Spiperone produced a dose-related inhibition of the hypothermic and corticosterone responses to gepirone. Spiperone also inhibited ipsapirone-induced changes in body temperature and hormone secretion. Although spiperone also blocked the buspirone-induced stimulation of corticosterone, it did not attenuate the hypothermic response to buspirone at the dose tested. (-) Pindolol, a potent 5-HT1A antagonist, prevented gepirone- and ipsapirone-induced hypothermia and corticosterone secretion. (-)-Pindolol also blocked the hypothermic but not the corticosterone response to buspirone. Ketanserin, a 5-HT2 antagonist, did not inhibit the hypothermic or corticosterone responses produced by these novel anxiolytic agents. It is concluded that buspirone, gepirone and ipsapirone produce hypothermia and increase plasma concentrations of corticosterone by activating 5-HT1A receptor mechanisms. PMID- 2901111 TI - Prostaglandin E1: a review. AB - Work on the structure of prostaglandin E1 (PGE1), isolated from natural sources, was completed 25 years ago (1). Shortly after, methods for the chemical synthesis of PG with their natural configuration were developed in the laboratories of the UpJohn Company (2) and of E. J. Corey (3) and, by the late sixties, PGE1 became widely available. The information since accumulated about its biological and clinical effects is more substantial than for any other PG. This review will draw together some of this information, focusing on recent studies of its mechanisms of action. PMID- 2901113 TI - Opioid and nicotinic medullary hyperalgesic influences in the decerebrated rat. AB - The effects of ethylketazocine (EKC) administered intraperitoneally and the nicotinic ligands (-)- and (+)-nicotine, (-)-cytisine, (-)-lobeline, and (+)-2 methylpiperidine administered into the 4th ventricle on the latency of the thermally evoked withdrawal reflex of the decerebrate rat were investigated. EKC administered intraperitoneally produced both hyperalgesia and analgesia. (-) Nicotine administered into the 4th ventricle produced a biphasic dose related effect on the latency of the withdrawal reflex; low doses produced a dose related analgesia while higher doses produced hyperalgesia. (-)-Cytisine and (-)-lobeline administered into the 4th ventricle produced biphasic effects. (+)-2 Methylpiperidine administered into the 4th ventricle produced a significant degree of hyperalgesia. Both the analgesic and hyperalgesic effects of (-) nicotine were antagonized by mecamylamine (1 mg/kg) and naltrexone (5 mg/kg). The hyperalgesic action of (+)-2-methylpiperidine was antagonized by naltrexone but not by mecamylamine. These observations suggest that there are both medullary opioidergic and nicotinic cholinergic mechanisms for modulating both analgesic and hyperalgesic processes and that nicotinic ligands have multiple mechanisms of action in the brain. PMID- 2901114 TI - Behavioural and neural-system analyses of the actions of anxiolytic drugs. AB - Anti-anxiety drugs (including benzodiazepines, barbiturates and alcohol) have a distinctive profile of behavioural action in animal species ranging from goldfish to chimpanzee. This profile may be summarised as a blockade of three kinds of reaction (behavioural inhibition, preparation for vigorous action, and increased attention to the environment) in response to any of three kinds of stimuli (novelty, stimuli associated with punishment, or stimuli associated with frustrative nonreward). On this basis, one may postulate a 'behavioural inhibition system' in the brain, responsible for organising the above reactions in response to appropriate stimuli; activity in this system would then constitute 'anxiety.' One may attempt to describe the brain structures that constitute the behavioural inhibition system either by enquiring about the neurochemical mode of action that is common to anti-anxiety drugs, or by seeking for structures with appropriate behavioural functions. The latter approach has implicated a number of structures in the limbic system (including the hippocampal formation, the septal area, and ascending monoaminergic pathways). Possible information-processing functions of these structures are described. PMID- 2901115 TI - Pharmacology and anxiety: inadequacies of current experimental approaches and working models. AB - Current models concerning the mechanisms of punishment suppression and anxiolytic drug effects fail to account for several treatment-test interactions in pharmacological studies. This applies in the first place to some important "double dissociation" phenomena. For example, in rats benzodiazepines are effective in conflict tests (Geller- and Vogel-type) but not in go-no go avoidance discriminations, while the converse is true in the case of antimuscarinics. Such a situation makes it necessary to postulate a plurality of mechanisms which can serve punishment suppression in various conditions, and can operate at least partly "in parallel" rather than "in series". In addition, different varieties of a particular test can show quite different sensitivities to the same type of agent and/or different profiles in studies using various types of anxiolytics and antagonists. This does not preclude the use of one or the other test as a convenient assay. It appears, however, that we have only limited knowledge on the mechanisms involved in the production of behavioral effects which are assumed to be typical of the anxiolytic profile. PMID- 2901116 TI - Preclinical studies with pyrazolopyridine non-benzodiazepine anxiolytics: ICI 190,622. AB - Tracazolate is a pyrazolopyridine anxiolytic that enhances the binding of [3H] flunitrazepam [( 3H]FLU) to brain tissue. The discovery that a metabolite of tracazolate, desbutyltracazolate, was a weak inhibitor of [3H]FLU binding led to the synthesis of a series of potent anxiolytics. From this series, ICI 190,622 emerged as a viable drug candidate, being a potent anxiolytic in rats and monkeys. This anxiolytic agent appears to produce only minimal sedation. Furthermore, ICI 190,622 appears less likely to potentiate the actions of ethanol than diazepam. ICI 190,622 is also a potent anticonvulsant (anti-metrazol ED50 = 1.1 mg/kg, PO) in rodents. Neurochemically, ICI 190,622 is similar to the benzodiazepine anxiolytics. In vitro, ICI 190,622 competitively inhibited [3H]FLU binding in cerebral cortex with an IC50 of 81 nM and was 4.3-fold more potent in the cerebellum (IC50 = 19 nM). This suggests a selectivity for the Type 1 benzodiazepine binding site. In contrast, diazepam showed similar affinities in both regions (cerebral cortex = 7 nM and cerebellum = 9 nM). Following oral administration, ICI 190,622 displaced [3H]FLU binding from cerebellar membranes more potently than diazepam (ED50 = 3 and 6 mg/kg, respectively, 1 hour after administration). Thus, ICI 190,622 should be an effective anxiolytic with significant advantages over benzodiazepines. PMID- 2901117 TI - Modifications of brain electrical activity after activation of the benzodiazepine receptor types in rats and rabbits. AB - The present study reports a comparative electroencephalographic (EEG) study of drugs belonging to different chemical classes which share the property to bind at benzodiazepine (BDZ) recognition sites. The EEG patterns are recorded from the neocortex of rats and rabbits as well as from dorsal hippocampus and red nucleus in rabbits after intravenous administration of diazepam (0.1-10 mg/kg), clonazepam (0.02-2.5 mg/kg), zopiclone (0.3-3 mg/kg), flunitrazepam (0.03-2.5 mg/kg), CGS 9896 (0.1-3 mg/kg), zolpidem (0.1-3 mg/kg) and Cl 218,872 (0.1-10 mg/kg). The most relevant differences are observed at the level of the neocortex. All drugs induced appearance of 7-12 Hz spindle bursts. On the contrary, the presence of 15-30 Hz waves (defined beta-like activity) mainly occurs after diazepam, clonazepam and zopiclone. Scarce beta-like activity is present after CGS 9896, zolpidem and Cl 218,872. According to the selectivity of these drugs for the various types of BDZ receptor, one can speculate that activation of BDZ2 is relevant for the appearance of the beta-like activity. Flunitrazepam, diazepam, and zolpidem increase the amplitude of the red nucleus waves. Such an effect is less marked after zopiclone and CGS 9896, whereas is almost absent after clonazepam and Cl 218,872. A reduction of the frequency is observed after flunitrazepam, diazepam, clonazepam, CGS 9896 and zolpidem, whereas it is almost absent after zopiclone and Cl 218,872. Finally, all drugs induce a reduction of the amplitude of the hippocampal theta rhythms, whereas after diazepam, flunitrazepam, zolpidem and CGS 9896 a slowing of the record also occurs. PMID- 2901118 TI - Electroencephalographic changes after short-term exposure to agonists of benzodiazepine receptors in the rat. AB - Naive rats receiving IV diazepam (10 mg/kg), flunitrazepam (2.5 mg/kg) and clonazepam (2 mg/kg) show electroencephalographic (EEG) changes consisting of lengthening of the spindle bursts (7-12 Hz; 200-300 microV) and appearance of 15 30 Hz waves (beta-like activity). These EEG manifestations are associated with signs of behavioral sedation (crouched, eyes open and myorelaxation) and stimulation (gnawing, running, ear twitches and sometimes wet-dog shakes), respectively. Bursts of 2-4 Hz waves can be occasionally observed associated with either marked sedation (lying down, eyes closed and presence of righting reflex) or sleep (stretched in the side with absence of righting reflex). Measurements of the periods spent by the animals in the two EEG patterns within the first hour after intravenous injection show the large preponderance of the spindle bursts over the beta-like activity. After the triazolopyridazine Cl 218,872 (10 mg/kg) the beta-like activity is almost absent, and in no case loss of the righting reflex can be observed. These agonists of BDZ receptors have been injected at the above reported doses for 5 days, once-a-day. At the 5th day, animals receiving diazepam exhibit a preponderance of the EEG and behavioral activation within the first hour after injection. Rats receiving flunitrazepam show a significant increase of the periods of stimulation and a slight decrease of the periods of sedation. These phenomena of "habituation" are absent in animals treated with clonazepam and Cl 218,872. PMID- 2901119 TI - Clinical pharmacology of non-benzodiazepine anxiolytics. AB - Non-benzodiazepine anxiolytics can be conveniently divided into those which are not primarily used as anxiolytics, those which pharmacologically but not chemically resemble benzodiazepines, and those which are novel both chemically and pharmacologically. The former include antidepressants, antipsychotic drugs, antihistamines and beta-adrenergic antagonists. The second group comprises a variety of compounds which act on the benzodiazepine/GABA complex and include alpidem and zuriclone. The most important of the non-benzodiazepine anxiolytics is buspirone, which seems to act on 5-HT mechanisms. The field of anxiolytic therapy is changing rapidly. New drugs are being introduced and the use of old ones questioned. It is hoped that drugs will be developed which are not only effective and safe with no sedation, but also with little or no propensity to dependence and abuse. PMID- 2901120 TI - Clinical studies with the new anxiolytic alpidem in anxious patients: an overview of the European experiences. AB - Alpidem is a new imidazopyridine compound which has been selected in animal pharmacology for its anxiolytic and anticonvulsant activity, and for its high therapeutic index. In healthy volunteers, alpidem was well tolerated up to doses of 300 mg and appeared to be devoid of CNS toxic effects. An extensive clinical development plan has been carried out in Europe to test its efficacy and safety in anxious patients. In a series of 5 double-blind placebo controlled parallel group studies, alpidem was administered as a single dose in a situation of stress induced anxiety where the stress was represented by diagnostic investigations such as gastroscopy, cardiac catheterisation or minor surgical operations. In these studies, 188 patients received placebo and 188 received alpidem; their anxiety was assessed before and after the drug administration by means of visual analogue scales and state anxiety inventories. Alpidem at 50 and 75 mg was significantly better than placebo in reducing stress induced anxiety. Alpidem was then administered to patients suffering from severe generalized anxiety in doses from 50 to 150 mg/day for 3-4 weeks in 3 double-blind placebo controlled studies: 127 patients received alpidem and 80 received placebo. Patients were assessed by means of rating scales and visual analogue scales. Alpidem did show an anxiolytic activity in this patient population and was well tolerated especially with regard to CNS side-effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901121 TI - Remoxipride--a new potential antipsychotic drug. Pharmacological effects and pharmacokinetics following repeated oral administration in male volunteers. AB - Remoxipride, a new potential antipsychotic drug, was administered over 4 days at two dose levels, 70 and 140 mg t.i.d., to eight healthy male volunteers. Pharmacokinetics, safety, tolerability, and effect on plasma prolactin levels were evaluated. Remoxipride exhibited essentially linear pharmacokinetics. Only minor deviations in biochemical and physiological safety parameters were found. The drug was well tolerated by all subjects at the 70 mg dose level. At 140 mg akathisia appeared in seven subjects. The drug induced a rapid and transient increase in plasma prolactin concentrations at both dose levels after single doses. During steady state, a significant reduction in the prolactin response was observed as compared to after the first dose. PMID- 2901122 TI - Anxiolytic effects of acebutolol and atenolol in healthy volunteers with induced anxiety. AB - Acebutolol (400 mg once daily), atenolol (100 mg once daily) and placebo were self administered to 12 healthy male volunteers in a double-blind crossover study. Each drug treatment was administered for 4 days so that subjects' plasma levels of the drug were at steady state. Subjects were tested on the 4th day. On each of the 3 test days subjects underwent an anxiety induction procedure involving both easy and difficult versions of the Stroop test and syntactic reasoning. Measures of state anxiety were taken during the difficult task, an easy version of the task and after a period of quiet relaxation. High, medium and low levels of anxiety corresponded to the three levels of task difficulty. Highly significant differences were exhibited in state anxiety between high, medium and low anxiety induction procedures with both Stroop test and syntactic reasoning. This was shown by highly significant main effects for task difficulty with both tasks. There was no significant anxiolytic action of either acebutolol or atenolol when compared to placebo (there were no drug effects or any interaction of drugs with task difficulty). There were no significant drug effects upon any of the cognitive test measures. Overall, there was no evidence of either anxiolysis or sedation with either of these two relatively hydrophilic drugs. PMID- 2901123 TI - Behavioral evidence for the role of noradrenaline in putative anxiolytic and sedative effects of benzodiazepines. AB - The effects of clonidine on the antianxiety and sedation of benzodiazepines (BZD) were assessed respectively in rats trained in a two-lever diazepam cue discrimination procedure and in single-lever fixed-ratio (FR) water-reinforced performance. Clonidine (10-60 micrograms/kg) significantly shifted to the left the dose-effect curves of diazepam in the discrimination paradigm. This treatment also shifted generalization dose-effect curves of the diazepam cue to chlordiazepoxide and CL 218,872 to the left in the drug discrimination procedure. The diazepam cue was antagonized in a dose-related manner by Ro 15-1788, but not by bicuculline. Clonidine also potentiated the rate-decreasing effects of diazepam on the FR schedule when the dose of diazepam was increased to 0.3 mg/kg, but not the milder rate-decreasing effect of CL 218,872 until the dose of CL 218,872 was increased to 10 mg/kg. The potentiating effects of clonidine on the stimulus control and depression of diazepam were antagonized by yohimbine. Yohimbine (1.0 mg/kg) also significantly shifted the dose-effect curve of diazepam cue to the right. Bicuculline (3 mg/kg) completely antagonized the rate decreasing effect of diazepam (1 mg/kg), but significantly potentiated the rate suppressant effect of clonidine (10 micrograms/kg). These results suggest that the central noradrenaline (NA) system may be involved not only in the antianxiety, but also the sadative action of BZD. The nature of NA involvement in relation to the different subtypes of BZD receptors requires further exploration. PMID- 2901124 TI - Antagonism by exifone, a new cognitive enhancing agent, of the amnesias induced by four benzodiazepines in mice. AB - Exifone is a novel compound proposed for treating cognitive decline associated with age and shows corrective effects in animal models of memory dysfunction. The present experiments examined the antagonism by exifone of the amnesias induced in mice in a passive avoidance test by four benzodiazepines: bromazepam, diazepam, lorazepam and triazolam. Subsequent experiments investigated the specificity of exifone's antagonism of benzodiazepine-induced amnesia by examining its interaction with the effects of the benzodiazepines in the staircase test (anxiolytic/sedative activity) and the electroshock test (anticonvulsant activity). The results indicated that exifone clearly antagonised the amnesias induced by the four benzodiazepines, but was without intrinsic effects in the staircase or electroshock test and did not antagonise the effects of the benzodiazepines in these two tests. These results suggest that exifone might be useful for decreasing the amnesias induced by commonly used benzodiazepines without affecting their anxiolytic or anticonvulsant activity. PMID- 2901125 TI - Objective and subjective assessments of the effects of flupentixol and benzodiazepines on human psychomotor performance. AB - The aim of this double-blind crossover trial was to compare the objective and subjective effects of flupentixol and lorazepam on human performance, and to reveal possible interactions between flupentixol and diazepam. Twelve healthy students received at 1-week intervals oral single doses of flupentixol 1 mg, flupentixol 2 mg, lorazepam 2.5 mg, placebo, and diazepam 15 mg alone and with flupentixol 1 mg. After the baseline measurements, the drugs were given in capsule form, and the tests were repeated 1.5, 3 and 4.5 h later. Diazepam was given at 1.5 h, to time its peak effect to coincide with that of lorazepam. Drug effects were measured objectively (two tracking tests, digit substitution, letter cancellation, flicker fusion, Maddox wing, tapping, memory) and subjectively (visual analogue scales, questionnaire). Blood samples were taken after each test time. Flupentixol 1 mg did not differ from placebo objectively or subjectively. Flupentixol 2 mg proved nearly inert objectively and on visual analogue scales. Lorazepam impaired objectively measured test performance, the clearest effects occurring at 3 and 4.5 h. It also impaired subjectively assessed performance. Diazepam impaired objective performance less than lorazepam, its effects peaking at 1.5 h after intake. Diazepam caused subjective drowsiness, clumsiness, mental slowness etc. as much as or more than lorazepam. The combination of 1 mg flupentixol and diazepam modified performance as much as diazepam alone. After the administration of 1 mg flupentixol, plasma concentrations were undetectable and levels after 2 mg were hardly detectable. Concentrations of lorazepam exceeded those of diazepam in direct bioassay, but they were much lower when bioassayed after solvent extraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901126 TI - Evidence for postsynaptic dopamine agonist effects of B-HT 920 in the presence of the dopamine D-1 agonist SKF 38393. AB - The ability of B-HT 920, a selective dopamine (DA) D-2 agonist, to stimulate postsynaptic DA receptors in brain was evaluated by assessing its ability to induce stereotypy and to increase locomotor activity in rats. When administered alone, B-HT 920 (0.03-3.0 mg/kg) did not induce stereotypy and produced only inhibition of locomotor activity, suggesting a lack of postsynaptic DA agonist actions. However, a different pattern of effects emerged when B-HT 920 was administered in combination with the selective DA D-1 agonist SKF 38393 (10 mg/kg): stereotypies (sniffing, licking, and gnawing) were induced and there was an inverted U-shaped function for locomotor activity. These data are consistent with the hypothesis that B-HT 920 has postsynaptic DA D-2 receptor agonist effects in normal rats that are revealed when D-1 receptor stimulation is also increased. PMID- 2901127 TI - Single-dose kinetics of the neuroleptic drug perazine in psychotic patients. AB - Eight male and two female unmedicated psychotic patients received 100 mg perazine orally and seven blood samples were taken within 25 h. Plasma levels of perazine and its demethylated metabolite were analyzed by HPLC with electrochemical detection. They exhibited large interindividual variations, with maximal concentrations as well as AUC values of perazine differing more than 10-fold. From the decay of plasma levels during the last 12-18 h half-lives were estimated to be between 7.5 and 10 h; they did not correlate with AUC. There was a significant positive correlation between AUC and age. Desmethylperazine was consistently present at lower concentrations than the parent drug during the first 12 h. PMID- 2901128 TI - Changes in behavioural responses to the combined administration of D1 and D2 dopamine agonists in normosensitive and D1 supersensitive rats. AB - The selective D1 receptor stimulant SKF 38393 dose-dependently increased grooming time in rats without affecting locomotor activity or eliciting stereotyped behaviour. The selective D2 receptor agonist LY 171555 induced a dose-dependent increase in rat motility, a marked decrease in grooming time and a low occurrence of stereotyped behaviour. Concurrent administration of the two selective agonists induced high-degree stereotyped responses and reductions in locomotor and grooming behaviours. Rats withdrawn from repeated treatment with the selective D1 receptor blocker SCH 23390 (0.05 mg/kg twice daily for 21 days; 7 days of washout) did not exhibit any change of locomotor and grooming responses to threshold doses of LY 171555 and SKF 38393 given alone or in combination. On the contrary, a significantly greater occurrence of high-degree stereotyped responses to the combination of the two selective agonists was observed. The data support the view that D1 and D2 receptors have a cooperative role in the generation of stereotypies and suggest that D1 receptor supersensitivity needs D2 stimulation to be revealed. PMID- 2901129 TI - The alpha 2-adrenoceptor antagonists idazoxan and yohimbine increase rates of DRL responding in rats. AB - Previous studies have reported that antidepressant drugs exert specific effects on responding maintained by DRL schedules of reinforcement, giving rise to increased frequencies of reinforcement. In order to investigate whether the alpha 2-adrenoceptor antagonist idazoxan would produce similar effects, the actions of this compound were compared with those of yohimbine, imipramine, mianserin and d amphetamine in rats trained to lever press for food reinforcement on a DRL 60-s schedule. Neither imipramine nor mianserin produced any effects on response rate or reinforcement frequency, except at the highest doses. In contrast, both idazoxan and yohimbine gave rise to dose-related increases in rates of responding and consequent decreases in reinforcement frequencies. Amphetamine also increased responding, but higher doses of this drug produced marked hyperactivity and stereotyped movements which were not observed after idazoxan and yohimbine. Although the present behavioural baseline was not sensitive to antidepressants, it demonstrated an unexpected activity of two alpha 2-adrenoceptor antagonists which deserves further investigation. PMID- 2901130 TI - Blockade of the discriminative stimulus effects of cocaine in rhesus monkeys with the D1 dopamine antagonist SCH 23390. AB - To investigate the role of D1 dopamine receptors in the discriminative stimulus effects of cocaine, two rhesus monkeys were trained in a two-lever, food reinforced, drug discrimination paradigm to discriminate cocaine (0.2 mg/kg, IM) from saline. Administration of various doses of cocaine resulted in a dose related increase in the percentage of responses that occurred on the drug appropriate lever. Administration of the D1 antagonist SCH 23390 20 min before cocaine reduced drug-appropriate responding from 100% to 0% in all subjects and increased by 4-8-fold the cocaine dose necessary to induce drug-appropriate responding. A mutual antagonism of the rate-decreasing effects of cocaine and SCH 23390 was also observed. These findings suggest that D1 receptors play a significant role in the discriminative stimulus and rate-decreasing effects of cocaine. PMID- 2901131 TI - The advent of malaria research in The Netherlands. PMID- 2901132 TI - [Science of labor--really useful?]. PMID- 2901133 TI - Somatostatin response to glucose before and after prolonged fasting in lean and obese non-diabetic subjects. AB - Insulin, glucagon, and somatostatin concentrations were measured in 7 lean and 7 obese non-diabetic subjects over 7 days of fasting. In addition each subject was given a 75 g oral glucose tolerance test after fasts of 12 h and 7 days. In lean subjects complete food deprivation induced a significant decrease in the circulating levels of both insulin and somatostatin, while glucagon nearly doubled by 48 h and then remained constant for the duration of starvation. Refeeding with oral glucose suppressed the increased plasma glucagon, but insulin and somatostatin responses were enhanced in comparison with the prefast values, as assessed by the integrated areas of change. In obese subjects peripheral insulin and somatostatin levels were significantly lowered, but plasma glucagon level was unchanged at the end of the starvation period. In the same group glucose-induced insulin and somatostatin release were greater than in the fed state. Suppression of plasma glucagon by glucose appeared less complete in obese than in lean subjects. It is concluded that prolonged starvation enhances D-cell responsiveness to glucose in lean and obese subjects. PMID- 2901134 TI - Cysteamine-induced reduction in gastrointestinal somatostatin: evidence for a region-specific loss in immunoreactivity. AB - Administration of cysteamine (beta-mercaptoethylamine; 2-aminoethanethiol) to rats has been shown to decrease the levels of somatostatin-like immunoreactivity (SLI) in the gastrointestinal tract and pancreas but its mode of action is unclear. In the current study the effect of cysteamine on gastrointestinal and pancreatic SLI has been studied using two antisera with different regional specificities. In addition, the in vitro effect of cysteamine on SS-14 and SS-28 has been studied by high-performance liquid chromatography (HPLC). Characterization of the two antisera (AS 26.3.2 and AS 1001) with a range of analogs of SS-14 revealed that both were directed against the midportion of the molecule but that AS 1001 was also sensitive to changes at the N- and C-termini. Tissue extracts from cysteamine-treated rats measured with AS 26.3.2 showed no significant change for the stomach, jejunum or pancreas but duodenal levels were reduced. With AS 1001 SLI levels were reduced in all tissues. Gel permeation chromatography of stomach extracts measured with AS 1001 showed a reduction in both SS-14 and SS-28. With AS 26.3.2 an increase in SLI eluting prior to the SS 14 peak occurred explaining why no significant reduction in total SLI was detected. With duodenal extracts the elution profiles with AS 1001 reflected the large reduction in total SLI whereas with AS 26.3.2 a smaller reduction occurred. Both SS-14 and SS-28 were reduced. HPLC analysis of SS-14 and SS-28 following incubation with cysteamine in vitro showed a time-dependent decrease in both somatostatin species with absorbance at 280 nm was measured. New peptide peaks which developed were not all detectable by radioimmunoassay with either antibody. The results suggest that cysteamine causes a change in the structure of somatostatin which probably first involves a reduction of the disulphide bridge and then the N- and C-terminal regions of the molecule thus making it unmeasurable by antisera sensitive to changes in these regions. PMID- 2901135 TI - Luminal receptors for bradykinin on the canine tracheal epithelium: functional subtyping. AB - Luminal addition of bradykinin (BK) to the open-circuited canine tracheal epithelium produces a biphasic response in transmucosal potential difference (P.D.): a rapid, transient decrease (dip) followed by a subsequent, more sustained increase (rise), both phases being associated with an increase in conductance. We have attempted to characterise the receptor subtype mediating the bradykinin response. Lys-bradykinin (Lys-BK) elicited a similar response, and its EC50 as judged from concentration-response relations was similar to that of BK. Cross-tachyphylaxis between the two peptides confirmed a common receptor. Des Arg9-BK (a B1-agonist) neither elicited a response nor inhibited responses to BK. The novel B2-antagonist [Thi6,9-D-Phe8]kallidin reversibly inhibited responses to both BK and Lys-BK. The rapid changes in P.D. (dips) were unaffected by Na+ removal, but were eliminated by replacing luminal Cl- with isethionate. Thus, BK, acting on B2-receptors, transiently increases anion permeability of the luminal membrane of the canine tracheal epithelium. PMID- 2901136 TI - [Response of growth hormone to the acute test using GH-releasing factor 1-29 in acromegaly. Comparison in the baseline situation and under treatment with prolonged-action somatostatin]. PMID- 2901137 TI - [Buprenorphine: pharmacologic and clinical aspects]. PMID- 2901138 TI - [Attraction of mosquitoes (Diptera: Culicidae) by the Cuban miniature CDC light trap using lactic acid as an additional attractant]. PMID- 2901139 TI - [Anatomo-clinical conference. Apropos of a case of Zollinger-Ellison syndrome]. PMID- 2901140 TI - [The blood pressure profile, or how to establish the minimal effective dose of an antihypertensive agent]. PMID- 2901141 TI - [Alpha-linolenic acid and its metabolites EPA and DHA]. PMID- 2901142 TI - [In situ hybridization histochemistry and its use in the neurosciences]. PMID- 2901143 TI - Subunit stoichiometry and interaction of F1-ATPase of beef heart mitochondria. AB - By incubating soluble F1 of the beef heart mitochondria with radio active 7 chloro-4-nitro-2,1,3-benzoxadiazole (14C)-NBD-C1 in the dark, a labeled F1 with NBD/F1 molar ratio of 1:1 (0.995:1) was obtained, but 98% of the ATPase activity was inhibited. The inactivated ATPase activity of the NBD-labeled F1 may be restored by DTT, suggesting that an essential tyrosine residue of F1 (O-NBD-F1) may be labeled. By exposure of O-NBD-F1 with 0.83 NBD label per F1 molecule and a stable 82.5% inhibition of the ATPase activity even in the presence of DTT. Urea PAGE analysis clearly showed that a 63.4% of the total radio activity was associated with the beta-subunit. In the beta-fraction from N-NBD-F1 only a 19.90 20% of the labeling was detected. It is calculated that F1 of the beef heart mitochondria contains 3 (2.63-2.64) beta-subunits. The results obtained are discussed in connection with the subunit-subunit and site-site interactions and three-site model for F1 catalysis proposal by Boyer and his group. PMID- 2901144 TI - Gallo meeting a mecca for AIDS researchers. PMID- 2901145 TI - [Treatment of open leg fractures using external fixation with a compression distraction apparatus]. PMID- 2901146 TI - [The regulation of growth hormone secretion]. PMID- 2901147 TI - Protective effects of selenium on acetaminophen-induced hepatotoxicity in the rat. AB - Experiments were undertaken to examine the ability of selenium to protect against acetaminophen-induced hepatotoxicity and to examine possible mechanisms for this protective effect. Pretreatment of male, Sprague-Dawley rats with sodium selenite (12.5 mumol Se/kg, ip) 24 hr prior to acetaminophen administration produced a significant protection against the hepatotoxic effects of acetaminophen as assessed by a decrease in the plasma appearance of alanine aminotransferase and aspartate aminotransferase activities following acetaminophen. This was accompanied by an increase in the hepatic glutathione levels in selenium-treated animals and an inhibition in the decrease in hepatic glutathione content observed in animals receiving hepatotoxic doses of acetaminophen. Selenium pretreatment decreased the in vivo covalent binding of acetaminophen metabolites to hepatic protein, but did not alter hepatic microsomal cytochrome P-450 content or NADPH cytochrome c reductase activity, suggesting that selenium does not significantly alter the metabolism of acetaminophen to reactive electrophilic metabolites by the cytochrome P-450-dependent mixed-function oxidase enzyme system. Selenium produced an increase in the activity of gamma-glutamylcysteine synthetase which may account for the increased glutathione availability in selenium-treated animals and increased the activities of glutathione S-transferase and glucose-6 phosphate dehydrogenase. Examination of the urinary metabolite profile in selenium-treated animals revealed that the urinary excretion of acetaminophen and its metabolites was significantly increased over a 72-hr period. The increase occurred in the AAP-glucuronide metabolite while parent AAP and AAP-sulfate were actually decreased in selenium-treated rats. No change in recovery was observed in the AAP-glutathione or AAP-mercapturate urinary metabolites. While the glutathione conjugating system is enhanced by selenium treatment, amelioration of acetaminophen toxicity is most likely the result of enhanced glucuronidation which effectively diverts the amount of acetaminophen to be converted by the cytochrome P-450 system to the toxic metabolite. PMID- 2901148 TI - Antagonism of bromobenzene-induced hepatotoxicity by the alpha-adrenergic blocking agents, phentolamine and idazoxan. AB - The coadministration of phentolamine, an alpha-adrenoreceptor antagonist, was found to be effective in antagonizing the hepatotoxicity produced by bromobenzene in B6C3F1 mice. Multiple doses of phentolamine, administered in dosages of 10 mg/kg, attenuated almost completely the acute lethality resulting from a 0.5 ml/kg dosage of bromobenzene. Consistent with this decline in lethality, the coadministration of phentolamine significantly altered the magnitude of hepatocellular necrosis, the elevation of serum alanine aminotransferase activity, and the glutathione depression normally produced by this dose of bromobenzene. These protective effects were not limited to phentolamine. Idazoxan, an adrenergic antagonist more specific for alpha 2-receptors, was equally effective in antagonizing the bromobenzene-induced hepatotoxicity. Measurements of serum catecholamine levels revealed that the administration of hepatotoxic doses of bromobenzene elevates serum epinephrine levels. Furthermore, the phentolamine antagonism of the bromobenzene hepatotoxicity could be correlated to elevated serum epinephrine levels in both a temporal and dose dependent manner. Although the mechanism of the phentolamine antagonism remains to be established, one promising hypothesis involves its prevention of an epinephrine-mediated compromise in the glutathione-dependent detoxification of bromobenzene. PMID- 2901149 TI - Antagonism of bromobenzene-induced hepatotoxicity by phentolamine: evidence for a metabolism-independent intervention. AB - A previous study has revealed that phentolamine markedly antagonizes the bromobenzene-induced hepatotoxicity and lethality in B6C3F1 mice. One potential mechanism by which phentolamine may diminish the bromobenzene-induced hepatotoxicity is by a direct or indirect interference with the metabolism of bromobenzene to toxic metabolites. In the present study, phentolamine cotreatment failed to alter the elimination of bromobenzene from serum or the distribution of bromobenzene to liver. This suggests that phentolamine cotreatment does not indirectly interfere with bromobenzene bioactivation secondary to changes in bromobenzene absorption, distribution, or elimination. Further, a phentolamine concentration 10- to 20-fold greater than those measured in vivo failed to alter the in vitro metabolism of bromobenzene to its ortho- and para-phenolic metabolites. It is believed that para-bromophenol represents the rearrangement product of the hepatotoxic 3,4-epoxide and that ortho-bromophenol is a product of the nonhepatotoxic 2,3-epoxide pathway. Thus, it appears that phentolamine does not antagonize bromobenzene-induced hepatotoxicity by inhibiting the formation of hepatotoxic intermediates, nor by enhancing metabolism via the nonhepatotoxic pathway. On the basis of these studies, we conclude that phentolamine antagonism of bromobenzene-induced hepatotoxicity occurs through a mechanism independent of bromobenzene bioactivation. PMID- 2901150 TI - Effects of AT-125 on the nephrotoxicity of hexachloro-1,3-butadiene in rats. AB - The role of gamma-glutamyl transpeptidase (gamma-GTP) in the nephrotoxicity of hexachloro-1,3-butadiene (HCBD) was studied using male Sprague-Dawley rats pretreated with AT-125 (Acivicin; L-(alpha S, 5S)-alpha-amino-3-chloro-4,5 dihydro-5-isoxazoleacetic acid). Inhibition of gamma-GTP by more than 95% did not affect urine output, glomerular filtration rate, or tubular reabsorption of filtrate, sodium, or glucose. Nephrotoxicity observed during the first 24 hr after HCBD was not decreased by inhibition of gamma-GTP and beyond 24 hr nephrotoxicity was increased, rather than decreased, in the AT-125-pretreated group. HCBD impairs glucose reabsorption and this was greatly increased in the AT 125-pretreated group, indicating that function of the initial segment of the nephron is impaired by HCBD. Since inhibition of gamma-GTP did not protect against HCBD nephrotoxicity, it is concluded that gamma-GTP inhibition does not limit the formation of metabolites(s) which cause HCBD nephrotoxicity. Therefore, distribution of gamma-glutamyltranspeptidase does not account for the selective nephrotoxicity of hexachloro-1,3-butadiene. PMID- 2901151 TI - [Clinical classification of traumatic teeth injuries]. PMID- 2901152 TI - [Effect of Argiope lobata venom and its components on L[3H)glutamate binding with locust muscle membranes]. AB - The Argiope lobata venom is shown to block synaptic potential at locust neuromuscular junctions and inhibit the high-affinity sodium independent L[3H]glutamate binding site in locust muscle membranes. The data obtained due to fractionation of venom evidence that it contains components which block synaptic potential and inhibit the binding of L[3H]glutamate (5 kDa and more) as well as components which block synaptic potential but do not inhibit the binding of L[3H]glutamate less than 5 kDa. These observations indicate that spider venom contains at least two components with different mechanism of action. PMID- 2901153 TI - [Subcutaneous tunnelling of epidural catheters]. PMID- 2901154 TI - [Undescended testis--when is optimal time for treatment?]. PMID- 2901155 TI - Renal proton ATPase activity. PMID- 2901156 TI - [Testing the effectiveness of a combination of glutamic and citric acid against the lethal effects of urea and ammonia in sheep]. PMID- 2901157 TI - Effects of pancreatic acinar cell surface antibodies and complement on isolated rat acinar cells in vitro. AB - Surface directed pancreatic acinar cell antibodies raised by immunization of rabbits with suspensions of viable isolated rat acinar cells were utilized to study immune cytolytic processes as a model of in vitro pancreatic injury. The antibodies produced were bound to rat pancreatic acinar cell surface determinants and significantly damaged freshly separated acinar cells by immune cytolytic mechanisms. Addition of complement accelerated the cytolytic effects on the target cells in a dose-dependent manner. The decline of acinar cells was dependent only on the presence of the immune cytolytic potential and not on the number of already damaged cells. Morphologic changes in the cells induced by the agents applied were revealed by both transmission and scanning electron microscopy. The presented experimental model seems a valuable tool for further investigations at the cellular level into the contribution of primarily occurring acinar cell injury in triggering the subsequent pathophysiological mechanisms initiating autodigestion of the pancreatic gland in the pathogenesis of acute pancreatitis. PMID- 2901158 TI - Immunocytochemical study of S-100 protein in human pituitary adenomas. AB - The S-100 protein was localized by immunocytochemistry in 70 pituitary tumors including 30 prolactin, 16 growth hormone, two corticotropin and 22 non functioning adenomas. Positive immunostaining was observed in only one case (prolactin adenoma). It is concluded that in functioning and non-functioning pituitary tumors there is no particular involvement of S-100 protein-containing cells, at least under the conditions of this study. PMID- 2901159 TI - Colonization of the rat liver by syngeneic tumor cells. An experimental approach by in vivo and in situ studies. AB - Syngeneic colon carcinoma cells and glioma cells were injected into the portal vein of BD IX rats. After various time periods the animals were sacrificed and the livers and lungs were fixed and prepared for histology. Atypical cells were observed in the liver 4 and 7 days after the injection of tumor cells, whereas distinct colonies of both colon carcinoma and glioma cells were demonstrated after 14 days. Lung metastases of both tumor cell types were seen after 14 and 30 days. Furthermore, injection of glioma and carcinoma cells into the tail vein gave detectable lung metastases after 7 and 4 days respectively. Intraperitoneal injection of tumor cells resulted in the accumulation of large tumor masses, particularly in the mesentery. By in situ perfusions of the liver with tumor cells included in the perfusion medium it was possible to establish that all the tumor cells were arrested in the course of 4 min. In contrast, normal rat leukocytes were not trapped in the liver, whereas trypsin-treated leukocytes were, suggesting the importance of trypsin-sensitive structures for binding to hepatic tissue. The binding of both glioma and carcinoma cells to the liver and the ensuing growth of tumor nodules in this organ indicate a lack of specificity on part of the malignant cell types for metastasis to the liver in the rat. Both tumor cell types colonized the first organ encountered after injection. PMID- 2901160 TI - N-terminal amino acid sequence analysis indicates that isolated atrial amyloid is derived from atrial natriuretic peptide. AB - Isolated atrial amyloid, the most frequent senile cardiac amyloid type, was chemically analysed. Amyloid fibrils obtained from a patient (NIP) were extracted and the predominant low-molecular-weight polypeptide (approximately 3.5 kDa, designated ASc2 NIP) was isolated by size exclusion high performance liquid chromatography in 60% formic acid. N-Terminal amino acid sequence analysis of this polypeptide was identical to that of the atrial natriuretic peptide alpha hANP for the first 12 residues determined. PMID- 2901161 TI - Signal transduction in cells following binding of chemoattractants to membrane receptors. AB - Binding of chemoattractants to specific cell surface receptors on human polymorphonuclear leukocytes (PMNs) initiates a variety of biologic responses, including directed migration (chemotaxis), release of superoxide anions, and lysosomal enzyme secretion. Chemoattractant receptors belong to a large class of receptors which utilize the hydrolysis of polyphosphoinositides to initiate Ca2+ mobilization and cellular activation. Receptor occupancy leads to phospholipase C mediated hydrolysis of polyphosphoinositol 4,5-bisphosphate (PIP2) yielding inositol 1,4,5-trisphosphate (IP3) and 1,2 sn-diacylglycerol (DAG). These products synergize to initiate cell activation via calcium mobilization (IP3) and protein kinase C activation (DAG). Pertussis toxin, which ADP-ribosylates and inactivates some GTP binding proteins (G proteins), abolishes all chemoattractant induced responses, including Ca2+ mobilization, IP3 and DAG production, enzyme secretion, superoxide production and chemotaxis. Direct evidence for chemoattractant receptor: G protein coupling was obtained using PMN membrane preparations which contain a Ca2+-sensitive phospholipase C. Hydrolysis of polyphosphoinositides at resting intracellular Ca2+ levels (100 nm) was only observed when the membranes were stimulated with the chemoattractant N-formyl methyl-leucyl-phenylalanine (fMet-Leu-Phe) in the presence of GTP. Myeloid cells contain two distinct pertussis toxin substrates of similar molecular weight (40 and 41 kD). The 41 kD substrate resembles Gi, whereas a 40 kD substrate is physically associated with a partially purified fMet-Leu-Phe receptor preparation and may therefore represent a novel G protein involved in chemoattractant stimulated responses. Metabolism of 1,4,5-IP3 to inositol proceeds via two distinct pathways in PMNs: (1) degradation to 1,4-IP2 and 4-IP1 or (2) conversion to 1,3,4,5-IP4, 1,3,4-IP3, 3,4-IP2 and 3-IP1. Initial formation (0-30 s) of 1,4,5 IP3 and DAG occurs at ambient intracellular Ca2+ levels, whereas formation of 1,3,4-IP3 and a second sustained phase of DAG production (30 s-10 min) require elevated cytosolic Ca2+ influx. The later peak of DAG, which is not derived from phosphoinositides, appears to be required for stimulation of respiratory burst activity. Products formed during activation can feed back to attenuate chemoattractant receptor-mediated stimulation of phospholipase C by uncoupling receptor-G protein-phospholipase C interaction. PMID- 2901162 TI - Limited short term effects on number of nuclei after electron irradiation of mouse bladder urothelium. A morphometric study. AB - By use of morphometry the number of urothelial nuclei per mouse bladder on days 1 and 7 after electron irradiation with 0, 10, 20 and 30 Gy was calculated. The results indicate only limited cell loss. PMID- 2901163 TI - Stereological studies of the parathyroids in the young rat with hypercalcemia induced by severe phosphate depletion. AB - In order to suppress the parathyroid glands by inducing hypercalcemia, young rats were fed a diet containing a low (0.02%) phosphate content. After 28 days blood samples were taken for estimation of serum calcium, phosphate and immunoreactive parathyroid hormone levels. Both parathyroids from each animal were subjected to serial sectioning so that the total glandular volume could be calculated by light microscopy. Volume and surface densities of cells and organelles were measured according to conventional stereological principles, so that the total volumes and surface areas could be estimated. Phosphate depletion caused marked growth retardation. The animals also developed hypophosphatemia, but in spite of pronounced hypercalcemia the levels of circulating immunoreactive parathyroid hormone remained unchanged. The volume of the parathyroids was reduced, but only to an extent commensurate with the reduced body mass. In the experimental group the volume density of cells was unchanged, but that of nuclei was increased; the volume density of Golgi complexes was reduced. The densities of the other cell components measured, namely the volume density of mitochondria and the surface densities of secretory cells, nuclear membranes and rough endoplasmic reticulum were unchanged. When the volumes and surfaces were expressed in absolute terms and related to total body mass, no differences between the groups were apparent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901164 TI - Detection of human cytomegalovirus DNA and viral antigens in tissues of different manifestations of CMV infection. AB - Biopsy and autopsy specimens from 22 patients with cytomegalovirus (CMV) infections were investigated by means of in situ hybridization (ISH) to detect viral DNA and by immunohistochemistry (IHC) to visualize viral proteins. Both methods proved to be valuable tools for histopathology. ISH sometimes recognized cells that did not show typical CMV inclusions. An antiserum against the full spectrum of viral proteins (non-infectious enveloped particles) detected most cytomegalic cells in disseminated and organ-limited infections. An antiserum against a recombinant polypeptide (XP1) was particularly useful in connatal CMV infections and organ-limited infections. We have demonstrated that IHC and ISH studies in parallel are the best approach to the detection of CMV infections in pathological specimens. PMID- 2901165 TI - Terminally differentiated postmitotic tumor cells in a rat rhabdomyosarcoma cell line. AB - A permanent rat rhabdomyosarcoma cell line (BA-HAN-1C) has been established, the phenotype of which is characterized by the coexistence of undifferentiated mononuclear cells and differentiated multinuclear myotube-like giant cells. The failure of attempts to separate these two cell types by repeated recloning procedures indicates their close histogenetic relationship and suggests that differentiation in this tumor proceeds in a similar manner to that in normal striated muscle where postmitotic myotubes arise from mononuclear myoblasts by fusion. The morphologically undifferentiated mononuclear tumor cells were shown to be actively proliferating and to incorporate thymidine methyl-3H(3H-TdR). The myotube-like giant cells neither incorporated 3H-TdR nor underwent mitosis or exhibited any clonogenic potential. After retransplantation into syngenic rats, tumor growth was markedly retarded when the tumor cell inoculum contained a high percentage of myotube-like giant cells. These data show that proliferative activity in this rhabdomyosarcoma cell line is confined to the mononuclear tumor cell compartment, the multinuclear myotube-like giant cells having withdrawn from the cell cycle and represent terminally differentiated postmitotic cells. This cell line should provide a valuable tool for further investigation of coherent aspects of proliferation and differentiation using various differentiation inducers. PMID- 2901166 TI - Chemically induced rhabdomyosarcomas in rats. Ultrastructural, immunohistochemical, biochemical features and expression of alpha-actin isoforms. AB - A series of 14 primary and two metastatic rat rhabdomyosarcomas (RMS) induced with nickel sulfide was studied by light microscopy, transmission electron microscopy, indirect immunofluorescence, avidin-biotin-peroxidase immunohistochemistry and two-dimensional gel electrophoresis. Monoclonal or affinity-purified polyclonal antibodies were used for the immunohistochemical demonstration of vimentin, desmin, alpha-smooth muscle (alpha-sm) actin and alpha sarcomeric (alpha-sr) actin. By histological and ultrastructural studies, four categories of RMS were diagnosed on the basis of the neoplastic cell types. These were: (1) well-differentiated RMS (n = 2), (2) pleomorphic RMS (n = 8), (3) embryonal RMS (n = 4), and (4) embryonal myosarcomas (n = 2). Immunohistochemically, all these neoplasms expressed desmin and alpha-sr actin, reflecting their rhabdomyoblastic origin. Two dimensional gel electrophoresis performed on five neoplasms demonstrated alpha, beta and gamma actins spots in all cases. This study demonstrates that the alpha-sr actin antibody represents a good marker for rhabdomyoblastic differentiation is useful in the diagnosis of RMS since it was present in all morphologically confirmed RMS and in two ultrastructurally undifferentiated sarcomas positive for desmin. Neoplastic cells positive for alpha-sm actin were noted in 11 confirmed RMS. Double indirect immunofluorescence showed that all alpha-sm and alpha-sr positive cells also contained desmin. Co-expression of alpha-sr and alpha-sm actins was studied in serial sections of formalin-fixed, paraffin-embedded tumor tissue. Both alpha-sm and alpha-sr actins were localized in some rhabdomyoblasts. This study confirms our previous observations in human tumors and shows, for the first time, that alpha-sr and alpha-sm actins can be present in the same neoplastic cell in vivo. PMID- 2901167 TI - Morphometric and cytochemical evaluation of clofibrate-induced peroxisomal proliferation in adult rat hepatocytes cultured on floating collagen gels. AB - The present ultrastructural morphometric and cytochemical studies demonstrate clofibrate induced changes in peroxisomes in adult rat hepatocytes maintained for 14 days in primary culture on floating collagen gels. Catalase activity and the number and diameter of peroxisomes were reduced in hepatocytes cultured for between 2/3 and 7 days. However, hepatocytes cultured for 7-14 days had well developed peroxisomes containing crystalloid nucleoids. The number of anucleoid peroxisomes in hepatocytes treated with 2 mM Na clofibrate increased with culture age, and by day 14 the number was 2.9 times greater than in freshly isolated hepatocytes. Catalase activity, as well as the number of nucleoid-containing peroxisomes were much greater in treated hepatocytes than in untreated controls, but decreased slightly with culture age. The diameter of peroxisomes was not reduced in the treated cells. These results suggest that the treatment with Na clofibrate is effective both for proliferation and maintenance of peroxisomes and for enhancing catalase activity. In treated hepatocytes, matrical plates were formed in peroxisomes from days 5 to 14 and the number of plate-containing peroxisomes increased with culture age. PMID- 2901168 TI - Multiple myeloma associated with multilobated plasma cell nuclei. AB - Ten cases of multiple myeloma are reported in which there were a large number of plasma cells with excessively convoluted or lobulated nuclei. These cases represent 3% of the 297 evaluable multiple myeloma patients treated at our institution over a 22-year period. All 10 had intermediate or advanced stage disease at the time of diagnosis, and all have died after a mean survival of 19.5 months. Ultrastructural features of 2 cases are described. When found in abundance, such cells can cause difficulty in establishing a morphologic diagnosis of multiple myeloma because of their resemblance to other cell types. Therefore, it may be necessary to perform immunoperoxidase staining and/or electron microscopy to confirm the plasmacytic identity of these cells. The findings add further support to the contention that the presence of excessive nuclear convolutions is not a completely reliable indication of T-cell, as opposed to B-cell, lineage. PMID- 2901170 TI - Well differentiated and small cell neuroendocrine carcinomas of the lung. Two related but distinct clinicopathologic entities. AB - Twenty-two resected pulmonary well differentiated neuroendocrine carcinomas (WDNC) were re-evaluated histologically as were 28 resected intermediate-small cell neuroendocrine carcinomas (IC-SCNC). WDNC were distinguishable from IC-SCNC by their consistently recognizable organoid architecture, and by the absence or limited extent of necrosis. Furthermore, WDNC could be subclassified into 3 subsets based upon the degrees of pleomorphism, local and vascular invasion, and stromal fibrosis, the mitotic count, and the extent of tumor necrosis. Whereas all those parameters were important in discriminating between WDNC and IC-SCNC, the quality of the organoid architecture, and the extent and pattern of necrosis emerged as the most significant. WDNC with the more aggressive histologic features (subset III) had, as a group, a distinctly worse clinical course that those displaying blander features (subsets I and II). Nevertheless, even subset III of WDNC had, as a group, a longer survival than similarly treated Stages I and II IC-SCNC. We conclude that the histologic spectrum of WDNC is broader than generally recognized. Moreover, 3 subsets of WDNC are definable based on conventional histologic criteria provided sufficient, well preserved samples are examined. Even the most aggressive subset of WDNC can be thus histologically discriminated from IC-SCNC, and, given comparable stages, has a better prognosis than the latter. PMID- 2901169 TI - Extracellular matrix of cultivated, poorly differentiated human gastric adenocarcinoma cells promotes attachment and spreading of mesenchymal cells. AB - To clarify interactions between carcinoma and mesenchymal cells, we examined the extracellular matrix-substance remaining on culture dishes after confluent growths of gastric carcinoma cells were removed with EDTA. The matrix synthesized by poorly differentiated adenocarcinoma cells (cell lines KATO-III and MKN-45) cultivated in serum-free medium has a fibroblast (cell line WI38)-attachment activity, which is not detected in the matrix synthesized by a well differentiated adenocarcinoma (cell line MKN-28). This activity was not observed in KATO-III-matrix extracted with 6 M urea, but could be detected in a 1% SDS extract from the remaining matrix on the culture dishes after 6 M urea extraction. The activity was abolished by treatment with pronase (16 micrograms/ml), trypsin (0.005%) or alkali, but was unaffected by collagenase (80 micrograms/ml, 4 h) or chondroitinase ABC (1 U ml, 1 h). It is conceivable that the fibroblast-attachment activity of the matrix produced by poorly differentiated adenocarcinoma cells is related to the proliferation of interstitial connective tissue in vivo. PMID- 2901171 TI - [Changes in serum ferritin levels after gallbladder surgery in patients with diabetes]. PMID- 2901172 TI - [Effect of the mosquito iridovirus on the calmodulin content of the larval tissues of the honeycomb moth]. AB - The influence of iridovirus infection on the content of calmodulin in cells of honeycomb moth was studied, and a significant increase in the content of calmodulin in the infected cells was established which may indicate increased transcription of this protein gene. PMID- 2901173 TI - [Bronchial hyperreactivity in bronchial asthma]. PMID- 2901174 TI - [Cloning and gene expression of the leukocytosis (lymphocytosis) stimulating factor of Bordatella pertussis in Escherichia coli by bringing the PT genes close to the lactose promoter of plasmid pUC19]. AB - The 4.7 Kb EcoRI-fragment of phase I B. pertussis 475 (serovar 1.2.3.) chromosome carrying all five genes of the pertussis toxin (PT) operon was cloned on plasmid pUC19 in E. coli. The resulting hybrid plasmid pRH119 contained the PT operon in the same orientation of transcription as the lac promoter of plasmid pUC19. Nevertheless, the expression of the PT operon was not observed even after induction with isopropyl thio-beta-D-galactopyranoside (IPTG), which suggested either the inability of the PT operon to work in E. coli, or the presence of a transcription terminator between the lac promoter and the PT operon in plasmid pRH119. The expression was determined by the incubation of the clones harboring plasmid pRH119 with antiserum to PT and their subsequent in situ treatment with 125I-labeled protein A. Three deletion variants of plasmid pRH119 were constructed with the aim of approaching the PT genes to the lac promoter: pRH121 (the 0.45 Kb KpnI-fragment deleted), pRH122 (the 0.95 Kb SalGI-fragment deleted) and pRH123 (the 1.35 Kb XbaI-fragment deleted). In all these cases different levels of expression were observed (but only in the presence of IPTG). Site KpnI in the 4.7 Kb fragment was found to be localized in the -57 b. p. region in relation to the PT promoter, i. e. to lie, seemingly, in the promoter zone; for this reason, the expression of the PT genes in plasmid pRH121 proved the existence of a transcription terminator between the lac promoter and the PT operon in plasmid pRH119.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901175 TI - [Detection of the gene sequences of the leukocytosis (lymphocytosis)-stimulating factor of Bordetella pertussis in Bordetella parapertussis and Bordetella bronchiseptica by using molecular hybridization]. AB - The 4.7 Kb EcoRI-fragment of phase I B. pertussis 475 (serovar 1.2.3) chromosome DNA carrying the pertussis toxin (PT) operon was cloned on vector plasmid pUC19 in Escherichia coli. Three fragments (1.14 Kb KpnI-PstI, 1.27 Kb PstI-PstI, and 0.96 Kb PstI-PstI) were obtained from the resulting hybrid plasmid, coded pRH119, by electrophoretic techniques and used as a combined molecular probe for analysis of the EcoRI-digested and PstI-digested chromosomal DNA of B. pertussis strain 475 in phase I, B. pertussis in phase IV, B. parapertussis strains 504 and 17903, B. bronchiseptica strain 214, and B. parapertussis strain 17903 (a convertant obtained by means of B. pertussis phage 134), as well as B. pertussis phage 134. Southern blot hybridization under the conditions of 100% DNA-DNA homology showed the presence of DNA sequences characteristic of the PT operon in all cases except the DNA of phage 134; moreover, the use of the above-mentioned probe made it possible to hybridize all EcoRI-fragments of chromosomal DNA, having the same molecular size (4.7 Kb). Consequently, the PT genes in the above Bordetella species were mapped in identical loci.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901176 TI - [Characteristics of the clinical picture and of neuromediator metabolism in reactive depression]. AB - The so-called "pure" depressive states in the structure of psychogenic diseases occur less frequently nowadays. Therefore, the pathomorphosis of mental disorders which has been observed recently in clinical manifestations of different mental diseases complicates the differential diagnosis. To obviate this difficulty one of the most important diagnostic methods, namely measurement of the blood levels of neuromediators (noradrenaline, acetylcholine) in patients with reactive depression was used to study the neuromediator metabolism which is most closely related to changes in the emotional sphere. This is of great significance for the understanding of mechanisms of the formation of the clinical pattern of various depressive states and approaches to the disease diagnosis. These characteristics may be of use in selecting the mode of therapy. PMID- 2901177 TI - [Neurohumoral regulation of immune homeostasis in alcoholic patients]. AB - The effect of neuromediators (DA, GABA) of the neostriatum on the immunogenesis has been studied in 50 noninbred white rats of both sexes weighing 150-200 g, using a new non-cannula method of microinjection of substances into the predetermined brain structures. The results obtained have demonstrated that stimulation of the dopaminergic or blocking of the GABA-ergic system mediated through the impact on the function of neurohormones and cyclic nucleotides increase the body's immunological resistance. In contrast, blocking of the dopaminergic or stimulation of the GABA-ergic systems via the same mechanisms adversely affect immunogenesis. On the basis of the elucidated neurohumoral and immunological impairments the author recommends a pathogenetic treatment of alcoholism taking into account the patients' clinical status. The author points to inadvisability of the use of neuroleptics and GABA-positive drugs for suppressing the pathological craving for alcohol. PMID- 2901178 TI - [Effect of psychotropic preparations on the properties of tubulin in the brain]. AB - Neuroleptics (chlorpromazine, triftazin, haloperidol) inhibited the tubulin polymerization on supernatant of rat brain proteins in vivo at concentrations which corresponded to the therapeutic ones. The electron microscope studies demonstrated that these drugs inhibited the assembly of tubulin in microtubules. As this effect was the same in vivo and in vitro, it was considered specific. Colchicine-binding capacity of tubulin was suppressed only at higher doses of tranquilizers (250 microM). Antidepressant drug melipramine inhibited neither tubulin polymerization in vivo nor its colchicine-binding activity in vivo or in vitro. PMID- 2901179 TI - [Torpid schizophrenia with a predominance of asthenic disorders]. AB - The article deals with the typology of asthenic disturbances that determine for a long time the clinical picture of slowly progressive schizophrenia. Two types of asthenia (extensive and limited) have been identified as a result. With regard to clinical peculiarities these manifestations can be collated respectively with "pseudoneurasthenia" and "autochtonous asthenia". The author has analyzed the dynamics of these variants of the asthenic symptom complex to which, with the progression of the process, disturbances of the non-delirious hypochondria type are added. The author has established the relationship between clinical features of asthenia and the degree of progression of the process and a differing structure of negative changes formed at late stages of the disease. The first type (extensive asthenia) is observed in the framework of slowly progressive neurosis-like schizophrenia with manifestations of a moderate asthenic defect. The second type (limited asthenia) is noted in psychopathy-like slowly progressive schizophrenia associated with signs of greater progression and psychopathy-like changes of the "verschoben-type" with intellectual reduction. PMID- 2901180 TI - Acute effects of medetomidine, a selective alpha 2-adrenoceptor agonist, on anterior pituitary hormone and cortisol secretion in man. AB - Single iv doses (25, 50 and 100 micrograms) of medetomidine, a selective alpha 2 adrenoceptor agonist of the imidazole type, were administered to 8 healthy male volunteers in a randomized, double-blind, placebo-controlled study. The concentration of hGH in plasma was powerfully and dose-dependently increased. The plasma level of cortisol was dose-dependently decreased, whereas TSH showed a slight but statistically significant increase. Plasma levels of PRL, FSH and LH were unaffected by the drug. Medetomidine appears to resemble other alpha 2 adrenoceptor agonists, notably clonidine, in its endocrine effects. Its high selectivity and short duration of action make it a suitable tool for studies of the physiology and pharmacology of alpha 2-adrenoceptors in man. PMID- 2901181 TI - Treatment of hyperthyroidism with a small single daily dose of methimazole. AB - A prospective randomized trial with the conventional divided doses (10 mg 3 times daily, N = 29) and a small single daily dose (15 mg once daily, N = 25) of methimazole for the treatment of Graves' hyperthyroidism was performed. Within 8 weeks, almost 80% of the patients in both groups became euthyroid. The mean time required to achieve the euthyroid state was 6.0 +/- 2.8 and 6.0 +/- 3.8 weeks, respectively. TSH binding inhibitor immunoglobulin was found in about 90% of the patients in both groups before methimazole treatment. However, a gradual fall of its levels was observed in nearly all patients after treatment. There was no difference in the mean levels of TSH binding inhibitor immunoglobulin between the two groups during therapy. We conclude that the single daily dose regimen of 15 mg of methimazole will control Graves' hyperthyroidism in most patients, and TSH binding inhibitor immunoglobulin levels decrease in this regimen in the same way as with the conventional divided dose regimen (10 mg 3 times daily). PMID- 2901182 TI - Effect of insulin on basal pancreaticoduodenal output of somatostatin in normal and diabetic dogs. AB - The effect of insulin on basal pancreaticoduodenal output of SRIH was investigated in vivo and compared in normal and alloxan diabetic dogs. The experiments were performed on anesthetized dogs having a T-shaped catheter inserted into the pancreaticoduodenal vein just at the exit of the pancreas for blood sampling. In normal dogs, an insulin infusion (1 IU/kg for 20 min) or an iv insulin injection (0.2 IU/kg over 30 sec) produced, before any change in glycemia, an immediate reduction of the venous pancreaticoduodenal output of SRIH. Then pancreaticoduodenal output of SRIH rose close to starting values and decreased again when blood glucose level became very low. In alloxan-diabetic dogs, insulin infusion (1 IU/kg for 20 min) also induced an immediate inhibitory effect on pancreaticoduodenal SRIH output; the effect was more transient and from 20 min, unlike in normal dogs, an increase in pancreaticoduodenal output of SRIH was observed. In conclusion, exogenous insulin induces an immediate reduction in pancreaticoduodenal SRIH secretion both in normal and diabetic dogs, independently of basal blood glucose level and before any change in glycemia. In contrast, the delayed effect is different: SRIH secretion is reduced in normal dogs, whereas it is enhanced in diabetic dogs. PMID- 2901183 TI - Ornithine decarboxylase and transglutaminase activities in rat placenta during pregnancy. AB - Ornithine decarboxylase (L-Orbithine carboxylase, E.C. 4.1.1.17) and transglutaminase (R-glutaminylpeptide: amine gamma-glutamyltransferase, E.C. 2.3.2.1.13), enzymes implicated in the regulation of growth processes, were studied in rat placenta during pregnancy; the specific activity of TGase increased from the 15th day until the 21st day of pregnancy while no significant difference of ODC activity was observed; moreover, the ODCase/TGase ratio decreased significantly in rat term placenta. PMID- 2901185 TI - 6th international meeting of the International Society for Developmental Neuroscience. 8-12 July 1986, Queretaro, Mexico. Program and abstracts. PMID- 2901184 TI - The synthetic peptide GRF (1-29)-NH2 with growth hormone releasing activity penetrates human epidermis in nitro. PMID- 2901186 TI - Serum gamma-glutamyltransferase in a Swedish female population. Age-related reference intervals; morbidity and prognosis in cases with raised catalytic concentration. AB - We determined the catalytic concentration of gamma-glutamyltransferase in serum from a population sample of 1408 women in seven age strata between 26 and 72 years. The range in healthy individuals for the different age groups was found to increase with age with a maximum of the central 0.95 fractile interval at 58 years (0.17-1.68 microk/l). The serum gamma-glutamyltransferase activity correlated with body mass index, blood pressure and concentrations of blood glucose and serum ferritin, triglycerides and cholesterol. During follow-up of women with gamma-glutamyltransferase activity greater than 1.20 microk/l, no woman developed any disease possibly related to the original finding of raised serum gamma-glutamyltransferase activity, several individuals being apparently healthy. Apparently, the serum gamma-glutamyltransferase assay is an unspecific indicator of several metabolic abnormalities. High values may be found in individuals in whom all commonly done investigations have given results within the health-associated reference interval. PMID- 2901187 TI - Modulation of cellular transglutaminase: protease-induced activation. AB - Multiple molecular forms of transglutaminase are found in cells and each form is widely distributed. We find a 95 K dalton enzyme associated with membrane fractions. A 50 K dalton enzyme occurs primarily in epidermis and hair follicles. Cells after treatment with proteases show greater transglutaminase activity. The activated enzyme in rat chondrosarcoma cells is one of 95 K daltons, whereas mouse epidermal cells and rabbit endometrium cells after protease activation display enzymes of both 95 K daltons and 50 K daltons. The 95 K dalton enzyme, but not that of 80 K daltons, can be activated by proteases or sulfhydryl compounds after cell lysis. In cells that undergo terminal differentiation, e.g., reticulocytes, megakaryocytes, monocytes, chondrocytes, and epidermal cells, the forms of transglutaminase are modulated. Our findings suggest that these modulations in differentiating cells are the results of transglutaminase post translational modifications that cause pronounced changes in catalytic activity. PMID- 2901188 TI - Transglutaminase, donor age, and in vitro cellular senescence. PMID- 2901189 TI - Searching for the function of tissue transglutaminase: its possible involvement in the biochemical pathway of programmed cell death. AB - Although several details are still missing, the biological role of two of the three well characterized transglutaminases in mammals, namely blood coagulation factor XIII and keratinocyte transglutaminase, is established. The function of the third one called the tissue type is still an enigma. Its constant localization in endothelial and smooth muscle cells of all organs, in heart muscle, in medullary interstitial and mesangial cells of kidney, and its induction in a number of other cell types under a variety of conditions suggest multiple functions. According to our results its participation in the biochemical pathway leading to programmed cell death (apoptosis), a basic cellular phenomenon of physiological significance, may be one of these functions. PMID- 2901190 TI - Modulation of cellular response to antigens by uteroglobin and transglutaminase. PMID- 2901191 TI - Transglutaminase-catalyzed crosslinking of an immunosuppressive and anti inflammatory protein secreted from the rat seminal vesicles. PMID- 2901192 TI - Macrophage transglutaminases: characterization of molecular species and measurement of enzymatic modification by cigarette smoke components. PMID- 2901193 TI - Implication of transglutaminase in mitogen-induced human lymphocyte blast transformation. PMID- 2901194 TI - Biosynthesis of factor XIII A and B subunits. PMID- 2901195 TI - Retinoid--regulated expression of tissue transglutaminase in normal and leukemic myeloid cells. PMID- 2901196 TI - Transglutaminase-mediated cross-linking of proteins and cell ageing: the erythrocyte and lens models. PMID- 2901197 TI - Post-translational modifications of eye lens crystallins: crosslinking, phosphorylation and deamidation. PMID- 2901198 TI - Differential growth requirements of several Leishmania spp. in chemically defined culture media. AB - 17 strains of Leishmania from 4 species: brasiliensis, mexicana, donovani and garnhami have been continually cultured at 26 degrees C, in the absence of proteins, in a medium containing salts, glucose, D-ribose, 2-deoxyribose, hemin, tricine, HEPES, 34 amino acids and intermediates of amino acid metabolism, 23 vitamins, 6 nucleotides and tetrahydrofolic acid. A wide variation in growth requirements was observed among leishmaniae which permitted the preparation of different minimum culture media for each Leishmania spp. Virulence of parasites was maintained after 30 passages in these chemically defined media. The requirements for differentiation to amastigotes also varied among the species as a function of the temperature of incubation and the protein content of the culture medium. Bovine serum albumin tryptic peptides substituted fetal bovine serum as growth factors at 30-34 degrees C. PMID- 2901199 TI - Interaction of Trypanosoma cruzi with macrophages. Involvement of surface galactose and N-acetyl-D-galactosamine residues on the recognition process. AB - The ability of the surface galactose (Gal)/N-acetyl-D-galactosamine (GalNAc) receptor of mouse peritoneal macrophages to recognize bloodstream trypomastigotes of Trypanosoma cruzi was examined. The parasite's uptake is improved by its desialylation and impaired by its treatment with Gal or GalNAc-binding lectins. Further incubation of asialoparasites with lectins for Gal-blockage (PNA and RCA I) reverses, in a dose-dependent way, 35-80% of the neuraminidase effect on the endocytosis of T. cruzi. Similar effects were observed when lectins for GalNAc blockage (PHA, WPA and DBA) were used. Asialoerythrocytes or galactosyl oligosaccharides added during the parasite-cell interaction assays, also competed with the normal or desialylated tryptomastigotes for receptors on the host cell surface, inhibiting their uptake and reversing the effect of neuraminidase. Although indirect, these results are strongly suggestive that the Gal/GalNAc recognition system of the macrophages is involved in the interiorization of T. cruzi. PMID- 2901200 TI - Suppression of cyclical development of Trypanosoma brucei brucei in Glossina morsitans centralis by an anti-procyclics monoclonal antibody. AB - Five hundred and sixty teneral male Glossina morsitans centralis were fed, at the height of parasitaemia, on a goat infected with Trypanosoma brucei brucei. Thereafter, the tsetse were divided into 4 equal groups. Group I was fed in vitro once weekly for 4 weeks and Group II twice weekly for 4 weeks on fresh defibrinated ox blood containing 2 mg/ml purified monoclonal antibody against T. b. brucei procyclics, while Group III was fed twice a week for 4 weeks on blood containing 2 mg/ml anti-T. vivax monoclonal antibody. The last group was fed on a rabbit. The tsetse were dissected on day 31 and the percent salivary gland infection rates observed were 18.2, 18.6, 39.8 and 40.8, respectively. In another experiment, 2 groups of tsetse, 120 per group, were fed on fresh defibrinated ox blood containing 2 mg/ml anti-T. b. brucei (test group) or anti-T. vivax (control group), on days 3, 6 and 9 following the infected feed. Dissection of the tsetse on day 31 revealed salivary gland infection rates of 0% in the test group and 6.5% in the control group. Thus the monoclonal antibody had a marked, specific suppression of the cyclical development of T. b. brucei in the tsetse vector. PMID- 2901201 TI - Infection rates in sterile males of morsitans, palpalis and fusca groups Glossina for pathogenic Trypanosoma species from East and West Africa. AB - Infection rates in sterile male Glossina morsitans centralis, G. austeni, G. palpalis palpalis, G.p. gambiensis, G. fuscipes fuscipes, G. tachinoides and G. brevipalpis for Trypanosoma vivax, T. congolense and T. brucei isolated from East and West Africa, were studied. Five groups of the sterile males, together with the five groups of sexually fertile males, of each of the respective species and subspecies were allowed to feed for 24 days on a Boran calf or goats infected with T. vivax or T. congolense, or with T. brucei for 34 days, after which they were dissected. The results showed that the infection of the pathogenic Trypanosoma species became better established in some tsetse species than in others. Also, the infection rates of T. vivax, T. congolense and T. brucei for sterile and sexually fertile males of any of the above Glossina did not differ significantly. These results indicate that releases of sterile male tsetse in the tsetse control programme will potentially increase the risk of trypanosomiasis during the period of tsetse releases in the affected areas, unless in the areas with low tsetse density the sterile male tsetse are rendered refractory to trypanosome infection prior to their releases while in the areas with medium to high tsetse densities, the resident tsetse populations are initially reduced with insecticides, traps and/or targets. PMID- 2901202 TI - Assessment of sensitivity of Trypanosoma congolense to isometamidium chloride: a comparison of tests using cattle and mice. AB - The sensitivities of 3 strains of Trypanosoma congolense to isometamidium chloride (Samorin) were determined in mice and cattle, with the objective of evaluating sensitivity testing in mice as a means of predicting curative doses in cattle. Comparison of mouse effective dose 80% (ED80) or curative dose 80% (CD80) values with cattle minimum curative dose (MCD) values demonstrated a wide variation between trypanosome strains. Although a mouse test may give a broad indication of the sensitivity of a strain, it cannot be used to predict curative doses for cattle. It was concluded that care should be exercised in extrapolating the results of a mouse test to cattle. PMID- 2901203 TI - Solid-phase extraction and ion-pair reversed-phase HPLC of isometamidium in bovine serum and tissues. AB - An analytical method has been developed for the determination of isometamidium in bovine serum and tissues. Samples were enzymatically hydrolysed and cleaned up on a solid-phase system (C8 Bond Elut column). The drug was chromatographed by an ion-pair reversed-phase technique using heptane sulphonate as a pairing-ion and triethylamine as a counter-ion reagent. Detection was by fluorescence at 593 nm (excitation = 380 nm). The method is more sensitive and specific than existing methods and it is currently being used in evaluating the pharmacokinetics of isometamidium in cattle. PMID- 2901204 TI - Bancroftian filariasis in the Igwun Basin, Nigeria. An epidemiological, parasitological, and clinical study in relation to the transmission dynamics. AB - A 12-month field and laboratory study was carried out to determine the epidemiology, clinical features, and transmission dynamics of bancroftian filariasis in the Igwun Basin, Nigeria. A total of 1,418 individuals (768 males, and 650 females) were examined for clinical signs of filariasis. 690 day provocative blood samples (DPS), and 728 night blood samples (NBS) were examined for microfilaremia. 14.3% of males and 11.1% of females were mf positive. 5.8% of DPS, and 19.5% of the NBS were mf positive. An overall microfilaria rate of 12.8% was recorded in the basin. Prevalence and microfilarial density increased with age. The highest average density of 35 mf/20 ml NBS occurred in the 40-59-year old male individuals. The mean microfilarial density in DPS and NBS were 7.9 and 28.0 per 20 ml blood in males, respectively, and 6.2 and 20.0 per 20 ml DPS and NBS in females, respectively. Disease rates of 55.5% were recorded for males, and 68.1% for females. The clinical signs observed were: Chyluria (9.1% for males, 16.7% for females); hydrocele (15.5%); elephantiasis (15.5% in males, 29.2% in females); and enlarged groin glands (15.5% in males, 22.2% in females). All clinical signs were associated with microfilariae. Anopheles gambiae s.I., and Culex pipiens s.I. were the two mosquito vectors identified. The estimated mean annual biting rates were 5508 and 10448 for A. gambiae s.I. and C. pipiens s.I., respectively. Their respective mean infection rates were 21.7% for A. gambiae s.I. and 22.7% for C. pipiens s.I.; with microfilarial densities of 4.1 and 6.6.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901205 TI - In vitro culture of Trypanosoma brucei gambiense isolated from human cerebro spinal fluid. Short communication. PMID- 2901206 TI - Trypanosome infection rates in tsetse midguts using a short-term in vitro culture technique. Short communication. PMID- 2901207 TI - Further studies on the Trypanosoma brucei group trypanosome, isolated from a patient infected in Anger-Didessa Valley, West Ethiopia, using the blood incubation infectivity test (BIIT). Short communication. PMID- 2901208 TI - Serum from the cotton rat (Sigmodon hispidus) lacks lytic activity against some Trypanosoma vivax stocks. Short communication. PMID- 2901209 TI - A survey of aminotransferase activities in bloodstream Trypanosoma brucei brucei. Short communication. PMID- 2901210 TI - Investigations of filarial worms of man in metropolitan Lagos. Short communication. PMID- 2901211 TI - Requirements of defined cultivation conditions for standard growth of Leishmania promastigotes in vitro. AB - The growth characteristics of L. chagasi (MHOM/BR/79/LI01) and L. braziliensis (MHOM/BR/72/1670), the causative agents of visceral and muco-cutaneous leishmaniases, respectively, were compared. Inoculum size clearly influences the growth course of both Leishmania species, whatever the culture medium used (serum supplemented media: GLSH or RPMI, and a chemically defined medium: LITR9). Cultures initiated with low concentrations failed to promote cell growth, while typical growth curves were obtained when higher promastigote inocula were used. For all the species tested, the higher the initial density of flagellates in the medium, the shorter were the periods covered by the latent and particularly by the logarithmic growth phases. In contrast, using constant inocula, variations in the volume of the incubation medium did not change the time-course of the different culture phases of either Leishmania species, provided that the ratio of incubation medium to total flask volume was comparable. Only cell division time significantly increased with the culture volume. We also determined whether or not the growth characteristics of the promastigotes of L. chagasi or L. braziliensis could be generalized to other members of the genus. Our results show that, whatever the culture medium used, L. infantum behaves in the same way as does L. chagasi, whereas L. panamensis, L. guyanensis, L. mexicana and L. amazonensis display growth patterns similar to that of L. braziliensis. PMID- 2901212 TI - [Late consequences of dental injuries]. PMID- 2901213 TI - Bacterial adhesion and pathogenicity. AB - Bacteria adhere to almost any surface via specific surface molecules of recognition through which a firm union is established for successful colonization of the host. Studies have shown that adhesion plays an important and critical early role in the pathogenesis of infectious diseases, and a series of adhesins have been well documented in a certain number of strains and species of bacteria of medical importance. Attempts have been made to interfere with, or prevent adhesion of, harmful bacteria to the host tissue, using receptor analogues or bacterial adhesin-vaccines as prophylactic measures to protect recipients from specific bacterial diseases. Although much success has been reported from such procedures in laboratory animals and livestock, extensive clinical trials are required to assess the efficacy of such procedures in humans. However, reports from limited studies have shown some encouraging results. Future studies must also be directed to the isolation and characterization of more adhesins and receptors and their specific interactions, which would provide fuller understanding of mechanisms of bacterial adhesion, especially at molecular level. PMID- 2901214 TI - The role of nitrates, beta blockers, and calcium antagonists in stable angina pectoris. AB - Numerous controlled studies have shown that nitrates, beta blockers, and calcium antagonists are effective in the treatment of stable angina pectoris. The pharmacokinetics, pharmacodynamics, and hemodynamic effects of these agents are different, and thus combination therapy offers additive improvement and also counterbalancing of the undesirable side effects of each drug. The choice of therapy depends on the severity of symptoms, associated diseases, compliance, side effects, and status of left ventricular function. The main mechanism of improvement is a decrease in myocardial oxygen consumption, though an increase in coronary blood flow is another potential reason for the use of calcium blockers. This review considers the properties of these drugs, their mechanism of action, and the results of randomized studies. PMID- 2901215 TI - Effect of maximal exercise testing on serum cholesterol in healthy subjects undergoing exercise training and on beta-adrenergic blockade. PMID- 2901216 TI - Contributions of neuroendocrine and local autocrine-paracrine mechanisms to the pathophysiology and pharmacology of congestive heart failure. AB - The degree of activation of neurohormonal mechanisms appears to depend on the severity and acuteness of cardiac impairment as well as the status of the extracellular fluid volume. Vasoconstrictive antinatriuretic mechanisms are markedly activated in severe decompensated cardiac failure. These are accompanied by parallel increases in endogenous vasodilatory natriuretic activities that modulate the powerful vasoconstrictive mechanisms. During chronic compensation, many of these neuroendocrine mechanisms returned to the baseline normal level. In addition to endocrine and neurogenic mechanisms, local autocrine-paracrine systems in the blood vessel wall may also contribute to the regulation of vascular tone. The role of these systems in congestive heart failure has not been systematically studied. It is possible that they may contribute to the long-term regulation of vascular tone and therefore may play an increasing role in the pathogenesis of ventricular remodeling, dilatation and progressive congestive heart failure. PMID- 2901217 TI - Regional blood flow responses to vasodilators and inotropes in congestive heart failure. AB - Regional blood flow and the distribution of cardiac output is an important aspect of the pathophysiology and pharmacology of human congestive heart failure. This study presents the cumulative experience and data from our laboratories with specific reference to (1) the regional blood flow responses, some rather unique, to various vasodilators and inotropes in patients with congestive heart failure (CHF), and (2) the pharmacophysiologic conclusions and concepts that have evolved from these data. Certain drugs and drug groups evoke rather consistent changes in the blood flow of certain organ systems in CHF. Renal blood flow is augmented by hydralazine, an effect that persists with chronic administration. The converting enzyme inhibitors, captopril and enalapril, increase renal blood flow; this implies that the renin-angiotensin II-aldosterone axis plays a major role in modifying renal blood flow and regional blood flow distribution in human CHF. Nitrates either reduce or do not change renal blood flow. Augmentation of hepatic splanchnic blood flow occurs after first-dose alpha 1-adrenoceptor blockade suggesting that alpha-adrenergic agonism plays an important role in modifying hepatic-splanchnic flow and the regional distribution of cardiac output in CHF. A number of drugs and drug groups increase limb blood flow (e.g., dobutamine, dopexamine, intravenous nitrates, nitroprusside, hydralazine and nifedipine). With respect to regional blood flow and the distribution of cardiac output in CHF, major differences have been shown to exist between drug groups, between drugs within a group and between different doses of a drug. Certain agents can cause a redistribution of systemic flow without changing cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901218 TI - Androgen receptors in boys with isolated bilateral cryptorchidism. AB - A study was conducted in boys with bilateral cryptorchidism, who were to undergo surgical orchiopexy, to determine if target-organ androgen insensitivity might play a role in the failure of the testes to descend into the scrotum. Nine boys older than 1 year in whom bilateral undescended testes was the only genitourinary abnormality were evaluated. Each subject was administered a six-week course of human chorionic gonadotropin (hCG), 3000 U/m2 of body surface area, intramuscularly injected daily for five days and then twice per week. Basal and hCG-stimulated levels of testosterone were normal. However, hCG administration failed to induce testicular descent in all cases. At the time of surgery, scrotal skin and testicular biopsy specimens were obtained for propagation of cells in tissue culture. Androgen receptor levels and binding affinity were normal for the androgen-specific ligands dihydrotestosterone and metribolone in both skin fibroblasts and testicular cells. In addition, 5 alpha-reductase activity was normal in scrotal skin fibroblasts. Nine boys with bilateral cryptorchidism and normal testicular androgen biosynthesis had normal androgen receptor-binding activity and 5 alpha-reductase activity in cultured scrotal skin fibroblasts and testicular cells. Therefore, bilateral maldescent of the testes in these boys with cryptorchidism was not due to androgen insensitivity. PMID- 2901219 TI - Usefulness of serum thyrotropin-binding inhibitory index measurements in infantile hypothyroidism. Relationship to serum thyrotropin concentrations. AB - Transplacental passage of thyrotropin (TSH)-binding inhibitory immunoglobulins may result in transient congenital hypothyroidism. We measured serum TSH-binding inhibitory index (TBII) in 11 infants with abnormal screening findings using a commercially available kit. Two of the infants, who were siblings, had markedly elevated TBII values (90% and 100%, respectively), as did their mother (89%, 100%), and had a clinical course consistent with transient antibody-mediated hypothyroidism. Four other infants had a borderline or mildly elevated TBII that was not present in maternal serum, suggesting that endogenous TSH was being measured in this assay. The TBII was measured in the sera of 18 additional children with primary hypothyroidism and in human TSH standards from 25 to 2000 mU/L. Increasing concentrations of TSH were associated with a linear increase in TBII. Measurement of TBII by this method may identify infants with transient antibody-mediated hypothyroidism, although simultaneous assessment of maternal serum is necessary. PMID- 2901221 TI - Acid suppression and ulcer healing: dichotomy, degree, and dilemma. PMID- 2901220 TI - Overnight comparable anacidity by standard large and half-single bedtime doses of H2 antagonists in duodenal ulcer patients: a clinical pharmacological study. AB - We continuously monitored 24-h intragastric pH in eight ulcer patients--who received orally at 10 PM in double-blind, randomized fashion either placebo, ranitidine 150 mg and 300 mg, or famotidine 20 mg and 40 mg, on five separate occasions--in order to determine whether half the commonly used bedtime doses of the H2 antagonists would suppress overnight acidity to the same extent as the large doses. Our results show that, during the nocturnal period (from 11 PM to 8 AM), significantly higher pH values were obtained with the large doses than with the half doses of both ranitidine (p = 0.00005) and famotidine (p = 0.00004). However, hydrogen ion activity was virtually nil with each H2 blocker dose regimen, and the percent inhibition of acidity over placebo was 100% for all of them (p = approximately equal to 0). Further more, with regard to the nocturnal period elapsed in min above 5.0 pH units, there was no significant difference between the two ranitidine doses (p = 0.39) and the two famotidine doses (p = 0.81). Therefore, the two dosing schedules of each H2 antagonist increased intragastric pH differently, but both the half and the standard large regimens produced similar overnight virtual anacidity. It is suggested that ranitidine and famotidine should be evaluated in the acute treatment of duodenal ulcer, using single bedtime doses half those commonly employed. PMID- 2901222 TI - Prevalence of HTLV-1 antibodies in hemodialysis patients in Japan. AB - The southwestern region of Japan is known as a very high endemic area of human T cell lymphotropic virus type 1 (HTLV-1), the etiologic agent for adult T-cell leukemia (ATL) and probable causative agent for tropical spastic paraparesis and its Japanese version, HTLV-1-associated myelopathy (HAM). Hemodialysis (HD) patients seem to be at high risk for HTLV-1 infection even in other regions of Japan because they sometimes receive multiple blood transfusions. We examined antibody against ATL-associated antigen (ATLA-Ab) in 1,132 HD patients, including 1,066 patients in nonendemic areas (Chubu and Tokyo) and 66 in a highly endemic area (Okinawa). The HD patients in Okinawa showed the highest prevalence, 21.2% (14/66), while those in the Chubu area showed the lowest, 1.1% (10/846), and those in the Tokyo area an intermediate value, 2.7% (6/220). The prevalence of HD patients in each area was significantly higher than that of local blood donors, reflecting an increased prevalence roughly corresponding to the respective endemic rate. The average prevalence of ATLA-Ab among the HD patients was 2.7% (30/1,132), which was similar to that of HBs antigen (3.2%). In the nonendemic areas, 15 of 16 patients with ATLA-Ab had a history of blood transfusions, showing a significant correlation to the presence of ATLA-Ab (P less than 0.01), although four had family histories related to the endemic area. The relative risk of the presence of ATLA-Ab for HD patients with a history of blood transfusions was calculated as 10.3. In the endemic area of Okinawa, the relationship to blood transfusion was not so close, probably masked by the high background prevalence. PMID- 2901223 TI - A new hypervariable marker for the human alpha-globin gene cluster. AB - We have located a highly polymorphic region of DNA approximately 100 kb upstream of the human alpha-globin genes (the alpha-globin 5' hypervariable region; 5'HVR). The element responsible is a minisatellite sequence comprising a variable copy number tandem repeat array of a G/C-rich 57-bp sequence. This increases the number of minisatellite elements in the vicinity of the alpha-globin genes to five, all of which share a region of sequence identity, thus raising questions concerning the distribution and origins of such tandem repeat sequences. The 5'HVR is highly polymorphic and, together with other hypervariable regions at this locus, provides a valuable genetic marker on the short arm of chromosome 16. PMID- 2901224 TI - Maternal duplication associated with gene deletion in sporadic hemophilia. AB - Sporadic occurrences of X-linked disorders can give insights into mutagenesis in man. In a case of sporadic hemophilia, associated with a partial deletion of the factor VIII gene, an unexpected inheritance pattern of gene rearrangements was observed. The factor VIII gene was found to be partially duplicated in the hemophiliac's mother. A pedigree analysis indicates that the mother has contributed both aberrant genes as well as the normal gene to her offspring. One simple model for the evolution of the deletion in this family is that the duplication is the precursor to the deletion. PMID- 2901225 TI - The gene CYP3 encoding P450pcn1 (nifedipine oxidase) is tightly linked to the gene COL1A2 encoding collagen type 1 alpha on 7q21-q22.1. AB - CYP3, the gene which encodes the hepatic cytochrome P450pcn1, the isozyme responsible for the metabolic oxidation of the calcium channel-blocking drug nifedipine, has recently been mapped to human chromosome 7 using somatic cell hybrids. Using multilocus linkage analysis in CEPH families, we examined the linkage of a cDNA probe (hPCN1) for CYP3 to the oncogene MET, the pro-alpha 2(1) collagen gene COL1A2, and the T-cell receptor beta-chain gene TCRB, together with three arbitrary loci D7S8, D7S13, and D7S16, defined by the anonymous DNA probes pJ3.11, pB79a, and p7C22, respectively. From 70 CEPH parents screened with a StyI RFLP for hPCN1, four informative families were found each with both parental and maternal grandparents and 6-11 children per family. Tight linkage emerged between CYP3 and COL1A2, with a maximum combined lod score of 5.72 at theta = 0, suggesting the most likely subchromosomal localization of CYP3 is 7q21.3-q22.1. PMID- 2901227 TI - Coexistence of thyroid-stimulating and thyroid-blocking antibodies in a patient with Graves' disease who had transient hypothyroidism. PMID- 2901228 TI - Isospora belli enteric infection in patients with human T-cell leukemia virus type I-associated adult T-cell leukemia. PMID- 2901226 TI - Characterization of the gene and protein of the common alpha 1-antitrypsin normal M2 allele. AB - The normal M2 variant of alpha 1-antitrypsin (alpha 1AT) was cloned from a genomic DNA library of an individual homozygous for this allele. Sequencing of all coding exons of the M2 gene revealed it was identical to the common M1(Val213) gene except for two bases (M1(Val213) CGT Arg101, M2 CAT His101; M1(Val213) GAA Glu376 M2 GAC Asp376). Analysis of the sequence of the M1(Val213) and M2 genes around residue 101 revealed the M1 Arg101----M2 His101 caused a loss of the cutting site for the restriction endonuclease RsaI. Using this enzyme, as well as 19-mer oligonucleotides probes centered at residues 101 and 376, evaluation of genomic DNA from 22 M1 alleles and 14 M2 alleles revealed that residue 101 was Arg in all M1 alleles and His in all M2 alleles, while residue 376 was Glu in all M1 alleles and Asp in all M2 alleles. Despite the differences in sequence at two amino acids, the M1(Val213) and M2 proteins function similarly as assessed by quantification of the association rate constant of each for their natural substrate neutrophil elastase. In the context that there are two mutations separating the M1(Val213) and M2 alleles, it is likely that there is another alpha 1AT variant that was an intermediate in the evolution of these genes. PMID- 2901229 TI - Effects of plasma amino acid and hormone levels on renal hemodynamics in humans. AB - The effect of plasma amino acid and hormone (insulin, glucagon, and growth hormone) levels on renal hemodynamics was studied in 18 healthy subjects. The following four protocols were employed: study 1, a balanced amino acid solution was infused for 3 h to increase plasma amino acid concentrations two to three times base line; study 2, the same amino acid solution was infused with somatostatin (SRIF) and infusions of insulin, glucagon, and growth hormone were concomitantly administered to replace the time sequence of increase in peripheral concentrations of these hormones as observed during study 1; study 3, the same amino acid infusion was administered with SRIF plus infusions of insulin, glucagon, and growth hormone to maintain plasma hormone concentrations constant at the basal level; study 4, SRIF was infused with insulin, glucagon, and growth hormone to reproduce the time sequence of increase of these hormones as observed in study 1; amino acids were not infused in this study. During study 1, glomerular filtration rate (GFR) and renal plasma flow (RPF) rose by 19 and 21%, respectively. During study 2 both the time sequence of and magnitude of rise in GFR and in RPF were similar to the changes observed during study 1. In studies 3 and 4 neither RPF nor GFR changed significantly from base line. These results indicate that 1) hyperaminoacidemia stimulates insulin/glucagon/growth hormone secretion and causes a modest rise in GFR and RPF; and 2) if hyperaminoacidemia is created while maintaining basal hormone levels constant or if plasma insulin/glucagon/growth hormone levels are increased while maintaining the plasma amino acid concentration at basal levels, neither RPF nor GFR rise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901230 TI - Guanosine 3',5'-cyclic monophosphate as a mediator of inhibition of renin release. AB - The role of guanosine 3',5'-cyclic monophosphate (cGMP) as an inhibitory mediator of tissue renin release was examined in two different in vitro preparations. In rat superficial cortical slices, renin release stimulated by isoproterenol (10( 5) M) was ablated by atriopeptin III (ANP, 2.1 x 10(-8) M), nitroprusside (NP, 10(-3) M), and 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 10(-3) and 10(-6) M). Arachidonic acid (10(-3) M)-stimulated renin release was also inhibited by ANP and 8-BrcGMP (10(-3) and 10(-6) M). Both ANP and NP increased tissue cGMP concentrations significantly (P less than 0.05), but neither had an effect on adenosine 3',5'-cyclic monophosphate (cAMP) concentrations. When methylene blue (10(-5) M), an inhibitor of guanylate cyclase, was added to slices incubated with isoproterenol and ANP, the inhibition of renin release by ANP was abolished. These results were confirmed in a preparation of isolated cultured rat juxtaglomerular cells. In these cells, isoproterenol induced a significant increase (58%, P less than 0.01) in renin release, which was inhibited by the addition of 8-BrcGMP (10(-6) M). These data demonstrate a direct inhibitory effect of ANP on isoproterenol- and arachidonic acid-induced renin release. The results with NP, 8-BrcGMP, and methylene blue suggest that cGMP is an intracellular mediator of this inhibition. PMID- 2901231 TI - Adrenergic and histaminergic neural interactions in dog paws. AB - The mechanisms underlying the vascular responses of superficial fibular nerve stimulation (SFNS) have not been defined. Right hindpaws of anesthetized heparinized dogs were vascularly and neurally isolated, enclosed in a volume recorder, and perfused with controlled pressure. Vascular volume (VV) (131I labeled albumin) and rate of tissue volume changes (VT) (plethysmography) were determined. SFNS increased blood flow resistance, reduced capillary filtration coefficient (CFC) and permeability-surface area product (PS) of 86Rb, increased VV, and reduced 131I-albumin recovery. VT increased at the rate of 3.35 +/- 0.45 ml/min. SFNS during terbutaline increased resistance, CFC, PS, and VV were unchanged, 131I-albumin recovery was complete, and VT increased at one-fourth the control rate. Phentolamine and yohimbine blocked all responses to SFNS. Prazosin with SFNS attenuated hemodynamic changes and VT increased to two-thirds of control, decreased VV, albumin, and Rb recovery but not PS and CFC. SFNS during pyrilamine maleate reduced VT increase to two-thirds of control rate and blocked decreases in PS and CFC. Metiamide did not change the SFNS responses, except to reduce vascular volume and VT. The combined histamine H1 and H2 blockers reduced VT increase to one-third of control and attenuated albumin loss, prevented histamine dilation, attenuated vasopressin and norepinephrine but not angiotensin constriction. SFNS stimulation increased precapillary resistance by alpha 1- and alpha 2-receptors and venous resistance by alpha 2-receptors and increased permeability by histamine release from endothelium. PMID- 2901232 TI - Support of arterial blood pressure by major pressor systems in conscious dogs. AB - The roles of the autonomic nervous system, vasopressin, and angiotensin II in support of blood pressure were evaluated in seven conscious, resting dogs while hydrated or dehydrated. Mean arterial blood pressure (MAP) was monitored, and the dogs were given hexamethonium to block autonomic ganglia. Thirty minutes later, they were given captopril, and after another 30 min, a vasopressin V1 antagonist, d(CH2)5TyrMeAVP, was given. The order okf administration of captopril and d(CH2)5TyrMeAVP was alternated in different experiments. Hexamethonium had no effect on steady-state MAP in either hydrated or dehydrated dogs. In hydrated dogs, the average MAP was 100 mmHg; d(CH2)5TyrMeAVP decreased MAP by approximately 12 mmHg, and captopril decreased MAP by 24 mmHg. The magnitude of the effect of these two inhibitors was independent of the order of their administration. Dehydration doubled the effect of d(CH2)5TyrMeAVP on MAP but had no effect on the response to captopril. The results suggest that 1) autonomic function is not essential for maintenance of arterial blood pressure in resting dogs; 2) during autonomic ganglionic blockade, arterial blood pressure is supported by both angiotensin II and vasopressin; and 3) dehydration increases the role of vasopressin in control of blood pressure. PMID- 2901235 TI - Acetylcholine to measure total vascular pressure-volume relationship. PMID- 2901233 TI - Pentobarbital anesthesia modifies pulmonary vasoregulation after hypoperfusion. AB - Our objectives were 1) to investigate the extent to which the pulmonary vascular response to increasing cardiac index after a period of hypotension and hypoperfusion (defined as reperfusion) measured in conscious dogs is altered during pentobarbital sodium anesthesia, and 2) to determine whether pentobarbital anesthesia modifies autonomic nervous system (ANS) regulation of the pulmonary circulation during reperfusion. Base-line and reperfusion pulmonary vascular pressure-cardiac index (P/Q) plots were generated by stepwise inflation and deflation, respectively, of an inferior vena caval occluder to vary Q in conscious and pentobarbital-anesthetized (30 mg/kg iv) dogs. During pentobarbital anesthesia, controlled ventilation (without positive end-expiratory pressure) allowed matching of systemic arterial and mixed venous blood gases to conscious values. Marked pulmonary vasoconstriction (P less than 0.01) was observed during reperfusion in pentobarbital-anesthetized but not in conscious dogs. Both sympathetic alpha-adrenergic receptor block and total ANS ganglionic block attenuated, but did not abolish, the pulmonary vasoconstriction during reperfusion in pentobarbital-anesthetized dogs. Neither sympathetic beta adrenergic receptor block nor cholinergic receptor block enhanced the magnitude of the pulmonary vasoconstrictor response to reperfusion during pentobarbital anesthesia. Thus, in contrast to the conscious state, the pulmonary vascular response to reperfusion is characterized by active, non-flow-dependent pulmonary vasoconstriction during pentobarbital anesthesia. This response is primarily, but not exclusively, mediated by sympathetic alpha-adrenergic vasoconstriction and is not offset by either sympathetic beta-adrenergic or cholinergic vasodilation. These results indicate, that, compared with the conscious state, pentobarbital anesthesia modifies pulmonary vasoregulation, during reperfusion following hypotension and hypoperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901234 TI - Time course of sympathetic denervation supersensitivity in canine ventricular recovery. AB - We studied the timing of the electrophysiological effects of sympathetic supersensitivity with chronically implanted electrodes in the anterior and posterior left ventricular free wall in 10 dogs. We produced denervation of the anterior wall in six dogs by application of phenol surrounding the anterior electrode. Drug infusions that were performed under pentobarbital sodium anesthesia included norepinephrine, isoproterenol, and methoxamine. In four controls there was no difference in response of the two sites. Presynaptic supersensitivity was manifest as early as 2 days and as late as 64 days by a parallel left shift (greater than or equal to 8.3 ms) in the norepinephrine dose to effective refractory period shortening response curve in the anterior compared with posterior left ventricle, P less than 0.01. The isoproterenol dose-response curve was also shifted to the left by 5.6 ms (P less than 0.01) but was manifest only after 10 days and only until 28 days from the denervation procedure. Local repolarization in the denervated areas shortened more than the innervated areas with both drugs. The methoxamine dose-response curve was flat, and the anterior denervated area was not different than the posterior-innervated area. We conclude that recovery properties in ventricular muscle demonstrate evidence of supersensitivity, which is neurotransmitter and beta- but not alpha-receptor specific. PMID- 2901236 TI - DSM-III personality disorders and the outcome of treated panic disorder. AB - Fifty-two patients with panic disorder who had been receiving active benzodiazepine treatment for 8 weeks were assessed by using the outcome measures of spontaneous and situational panic attacks, scores on the Hamilton scales for anxiety and for depression, and scores on self-rated disability scales. Although spontaneous panic attacks were not affected by the presence of any personality disorder, the remaining outcome measures showed a strong and negative association with DSM-III antisocial, borderline, histrionic, and narcissistic personality disorders. There was also a mild negative association with avoidant personality disorder. A subgroup of patients with both major depression and panic disorder appeared more strongly affected. PMID- 2901237 TI - Neuroleptic malignant syndrome and malignant hyperthermia. PMID- 2901238 TI - Treatment of tardive dyskinesia. PMID- 2901239 TI - Molecules on activated human T-cells. AB - Recent technical advances in immunology (such as the development of monoclonal antibodies, FACS analysis, molecular biology techniques, etc.) have enormously expanded our understanding of the process of T-cell activation. In this paper, we review some of the characteristics of surface molecules of activated human T cells. PMID- 2901240 TI - Dose-response curves for succinylcholine: single versus cumulative techniques. AB - This study was performed to determine the potency of succinylcholine using the single-dose technique, and to test the ability of the cumulative dose technique for generating dose-response data. Thirty-eight adult patients received single doses (n = 18), cumulative doses (n = 10), or cumulative doses of succinylcholine with an infusion to replace metabolized drug (n = 10). During opiate-thiopental nitrous oxide anesthesia the force of contraction of the adductor pollicis in response to train-of-four stimulation was measured and recorded. Linear regressions were obtained between the logit transformation of neuromuscular blockade and log dose. Similar potencies were obtained with single dose and cumulative dose with infusion techniques with an ED90 of 0.27 +/- 0.03 and 0.26 +/- 0.02 mg/kg (mean +/- SEM) respectively. However, cumulative dose without infusion significantly underestimated potency with an ED90 of 0.42 +/- 0.06 mg/kg (P less than 0.05 compared with the other two techniques). It is concluded that cumulative dose techniques can be accurately employed to determine the potency of succinylcholine if an infusion is utilized to compensate for eliminated drug. The data suggest that clinically used doses of succinylcholine (1.0-1.5 mg/kg) are equivalent to 3-5 times the ED90 and may explain the excellent intubating conditions provided by this drug. PMID- 2901241 TI - Urinary retention following spinal opiates. PMID- 2901242 TI - Restriction fragment length polymorphism of DQ and DR class II genes of the bovine major histocompatibility complex. AB - DQ alpha, DQ beta, DR alpha and DR beta class II genes of the bovine major histocompatibility complex (MHC) were investigated by Southern blot hybridizations using human probes. Hybridizations of these probes to genomic DNA, digested with PvuII or TaqI, revealed extensive restriction fragment length polymorphisms (RFLPs). The polymorphisms were interpreted genetically by analysing a family material, comprising five sires, 48 dams and 50 offspring, and a population sample comprising 197 breeding bulls. The analysis resolved 20 DQ alpha, 17 DQ beta, 5 DR alpha and 25 DR beta RFLP types. The segregation data were consistent with simple Mendelian inheritance of the RFLPs. The analysis of the bull sample showed that it is possible to apply the RFLP method for routine typing of class II polymorphism in population samples. The linkage disequilibrium in the DQ-DR region was found to be extremely strong as only about 20 DQ and about 30 DQ-DR haplotypes were observed despite the large number of possible haplotypes. Close linkage to the blood group locus M was also found; the M' allele occurred in strong linkage disequilibrium with the class II haplotype DQ1BDR alpha 4DR beta 1B. A population genetic analysis of the DQ data in the sample of breeding bulls revealed that the frequency of homozygotes was significantly lower than Hardy-Weinberg expectation and that the allele frequency distribution deviated significantly from the one expected for selectively neutral alleles. PMID- 2901243 TI - [Treatment strategies of psychotic states using low-dose neuroleptics: immediate and long-term course]. AB - Low doses of potent neuroleptics are introduced. Different strategies of treatment using low doses in schizophrenia are described. Long term effects on relapse development of supersensitivity psychosis and compliance issues are discussed. PMID- 2901244 TI - [Solian: evaluation of 10 years' experimentation and clinical practice]. PMID- 2901245 TI - [Bronchial carcinoid tumors in children. Apropos of 2 cases]. PMID- 2901246 TI - Surgeons' attitudes to the operative management of duodenal ulcer perforation and haemorrhage. AB - The currently preferred operative management of duodenal ulcer haemorrhage and perforation was assessed by means of a questionnaire sent to 274 consultant general surgeons in England. A 70% response rate was achieved. Simple closure, with or without H2 antagonist treatment, was the most popular management of a perforated acute duodenal ulcer. For perforation of a chronic duodenal ulcer occurring during H2 antagonist therapy, truncal vagotomy and drainage was the definitive procedure of choice. There was no consensus about the operative management of perforation complicating non-steroidal anti-inflammatory drug treatment in the elderly patient. Proximal gastric vagotomy appears to have few advocates in the definitive management of either duodenal ulcer perforation or haemorrhage. Of our sample 70% selected truncal vagotomy and drainage with underrunning of the ulcer as the operative treatment of choice for bleeding. Endoscopic coagulation appears to be used only rarely. PMID- 2901247 TI - Fumonisins--novel mycotoxins with cancer-promoting activity produced by Fusarium moniliforme. AB - Cultures on corn of Fusarium moniliforme MRC 826 are known to cause leukoencephalomalacia in horses and to be toxic and hepatocarcinogenic in rats. Culture material of this F. moniliforme isolate has also been shown to exhibit cancer-promoting activity in a short-term cancer initiation-promotion bioassay with diethylnitrosamine-initiated rats and the induction of gamma-glutamyl transpeptidase-positive (GGT+) foci as an endpoint after 4 weeks of promotion. This bioassay was used as a monitoring system to isolate cancer-promoting compounds from cultures of F. moniliforme MRC 826. Culture material was successively extracted with ethyl acetate and CH3OH-H2O (3:1). Most of the cancer promoting activity was recovered in the CH3OH-H2O extract and remained in the aqueous phase following partitioning of this extract between CH3OH-H2O (1:3) and CHCl3. The CH3OH-H2O fraction was chromatographed on an Amberlite XAD-2 column, and the active fraction was eluted with CH3OH. This fraction was chromatographed on a silica gel column with CHCl3-CH3OH-CH3COOH (6:3:1) as eluent and further purified on a C18 reverse-phase column. Two pure compounds were isolated, and these have been chemically characterized and given the trivial names fumonisin B1 and B2. At least 2 g of the major compound fumonisin B1 was purified from 1 kg of culture material. Fumonisin B1 in the diet (0.1%) significantly (P less than 0.001) induced the formation of GGT+ foci in the livers of initiated as well as noninitiated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901248 TI - Kinetic characterization, stereoselectivity, and species selectivity of the inhibition of plant acetyl-CoA carboxylase by the aryloxyphenoxypropionic acid grass herbicides. AB - The selective grass herbicides diclofop, haloxyfop, and trifop were found to be potent reversible inhibitors of acetyl-CoA carboxylase from the susceptible species barley, corn, and wheat. Kis values with variable concentrations of acetyl-CoA ranged from 0.01 to 0.06 microM at pH 8.5 depending on the species of grass. Inhibition of the wheat enzyme by diclofop was noncompetitive versus acetyl-CoA with Kis less than Kii and noncompetitive versus MgATP and bicarbonate, but with Kis approximately equal to Kii. Since the apparent inhibition constant was most sensitive to the level of acetyl-CoA, these compounds probably interact with the transcarboxylase site rather than the biotin carboxylation site. With the wheat enzyme the Kis value for the R-(+)-enantiomer of trifop was 1.98 +/- 0.22 times lower than that of the racemic mixture. This confirms the stereoselectivity observed in the whole plant. The enzyme from tolerant broadleaf species (spinach and mung bean) was much less sensitive to these herbicides (Kis values varied from 16 to 515 microM). These data confirm that acetyl-CoA carboxylase is the site of action for the aryloxyphenoxypropionic acid herbicides and may explain their selectivity for monocotyledenous species. PMID- 2901250 TI - [Pathways of the synthesis of glutamic acid by cephalosporin C-producing Acremonium chrysogenum]. AB - There were observed two pathways of glutamic acid formation in two strains of Acremonium chrysogenum differing in the production levels of cephalosporin C. The pathway involving glutamate dehydrogenase is known. The other pathway involved amination catalyzed by glutamine synthetase. Activity of both the enzymes during intensive synthesis of the antibiotic was higher in the highly productive strain. Under conditions of limited nitrogen content in the medium production of glutamate during the antibiotic biosynthesis depended on glutamine synthetase. When there was an excess of nitrogen in the medium the main role in production of glutamic acid at the phase of cephalosporin synthesis was played by the other enzyme i. e. glutamate dehydrogenase. By the dynamics the curve of the glutamate dehydrogenase activity correlated with that of the antibiotic production. PMID- 2901249 TI - Adjunct endarterectomy of the left anterior descending coronary artery. AB - During a three-year period, complete revascularization of diffusely diseased left anterior descending (LAD) coronary arteries was accomplished by extensive endarterectomy in conjunction with bypass grafting in 37 patients in whom conventional bypass was not feasible. This group constituted 7.0% of all patients undergoing nonemergency coronary revascularization during this period. The left internal mammary artery was used to bypass the endarterectomized LAD artery in 22 patients. There was 1 (2.7%) operative death and 1 perioperative myocardial infarction. At follow-up, which was 100% with a mean of 41.4 months, all endarterectomy patients were in New York Heart Association Functional Class I or II. Twenty-four endarterectomy patients underwent first-pass radionuclide angiographic stress testing 20 months after operation. Twenty patients (83%) had excellent postoperative exercise tolerance, achieving 5 to 7 mets on treadmill testing. Left ventricular functional reserve was preserved, as evidenced by an increase of global ejection fraction from 48 +/- 15% at rest to 59 +/- 18% (p less than 0.005) with exercise. A similar increase was measured in the proximal and distal anterior wall segmental ejection fractions. No difference in response to exercise was found between the internal mammary artery and the vein graft groups. Thus, complete revascularization of the diffusely diseased LAD artery can be accomplished by adjunct endarterectomy without added morbidity or mortality and with excellent functional results. PMID- 2901251 TI - Methylphenidate-induced information processing dysfunction in nonschizophrenic patients. AB - To examine the relationship of aminergic overactivity to information processing, we gave methylphenidate hydrochloride, oxazepam, or placebo to 12 nonpsychotic patients in one-week blocks in a double-blind, randomized design. Methylphenidate induced a pattern of information processing dysfunction similar to that seen in schizophrenic patients, strengthening the linkage of the schizophrenia information processing dysfunction-aminergic overactivity relationship. Further, the time course of the observed deficits in both schizophrenic and methylphenidate-induced states is strikingly compatible with the temporal mapping pattern of monoaminergic neuronal systems. More research is needed to identify definitively the aminergic influences on attentional functioning. A psychophysical task-pharmacologic probe strategy should prove useful. PMID- 2901252 TI - The effect of neuroleptics and tardive dyskinesia on smooth-pursuit eye movement in chronic schizophrenics. AB - We sought to determine whether such state-related factors as neuroleptic treatment and facio-oral tardive dyskinesia (TD) influence smooth-pursuit eye movement (SPEM) in chronic schizophrenics. The design involved 100 schizophrenics, 64 of whom showed "abnormal" eye tracking. Experimentally drug withdrawn patients, some of whom were clinically relapsed, were compared with control patients who continued taking medication in prewithdrawal and postwithdrawal SPEM tests. All groups showed a slight worsening in eye-tracking performance on two postwithdrawal tests, but significant group-by-test session "interactions" were not demonstrable. We also determined that patients with TD tend to substitute large, nontracking saccades for SPEM to a significantly greater extent than nondyskinetic patients. Our findings strengthen the supposition that impaired SPEM is a trait in many schizophrenics but suggest that patients with TD be excluded in future studies of SPEM addressed to trait issues. PMID- 2901253 TI - Who should receive clozapine? PMID- 2901254 TI - [H2-Antihistaminics. 39. Basic substituted aryloxyalkylguanidine derivatives and analogs with H2-antagonistic action]. PMID- 2901255 TI - [Effect of dietary alpha-linolenate/linoleate balance on the formation of leukotrienes in rat polymorphonuclear leukocytes]. PMID- 2901256 TI - [Recovery of the spermatogenic layer]. PMID- 2901258 TI - News from Washington AIDS meeting 1987. PMID- 2901257 TI - Alzheimer's disease. Aminergic-cholinergic alterations in hypothalamus. AB - To better understand the role of the hypothalamus in Alzheimer's disease (AD), we have measured dopamine, norepinephrine (NE), and serotonin (5HT) levels, tritiated spiperone and tritiated serotonin blinding, and choline acetyltransferase (ChAT) and acetylcholinesterase activity in seven subregions of the hypothalamus from 18 normal control subjects and ten patients with AD. We have found a significant reduction of 5HT in the anterior hypothalamus, lateral hypothalamus, and posterior lateral hypothalamus and a decline in spiperone binding in the anterior hypothalamus of patients with AD. The ChAT activity was found to be diminished only in the posterior lateral hypothalamus of patients with AD. No NE or dopamine alterations were found in any region of the AD hypothalamus. In the normal hypothalamus, dopamine, NE, and 5HT were found to be regionally distributed. Our study documents region-specific neurotransmitter abnormalities in the AD hypothalamus and raises the question of the relationship of these changes, especially in 5HT, to some of the noncognitive clinical alterations observed in AD. PMID- 2901259 TI - Enzymatically inactive forms of acetyl-CoA carboxylase in rat liver mitochondria. AB - Biotinyl proteins were labelled by incubation of SDS-denatured preparations of subcellular fractions of rat liver with [14C]methylavidin before polyacrylamide gel electrophoresis. Fluorographic analysis showed that mitochondria contained two forms of acetyl-CoA carboxylase [acetyl-CoA:carbon dioxide ligase (ADP forming) EC 6.4.1.2], both of which were precipitated by antibody to the enzyme. When both forms were considered, almost three-quarters of the total liver acetyl CoA carboxylase was found in the mitochondrial fraction of liver from fed rats while only 3.5% was associated with the microsomal fraction. The remainder was present in cytosol, either as the intact active enzyme or as a degradation product. The actual specific activity of the cytosolic enzyme was approx. 2 units/mg of acetyl-CoA carboxylase protein while that of the mitochondrial enzyme was about 20-fold lower, indicating that mitochondrial acetyl-CoA carboxylase was relatively inactive. Fractionation of mitochondria with digitonin showed that acetyl-CoA carboxylase was associated with the outer mitochondrial membrane. The available evidence suggests that mitochondrial acetyl-CoA carboxylase represents a reservoir of enzyme which can be released and activated under lipogenic conditions. PMID- 2901260 TI - Effect of 2-hydroxy-5-nitrobenzyl bromide on proton translocation by the mitochondrial H+-ATPase. AB - 2-Hydroxy-5-nitrobenzyl bromide, a highly reactive reagent towards tryptophan residues in proteins, is shown to activate the passive proton flux through the inner mitochondrial membrane of bovine heart submitochondrial particles (ETPH). When added at low concentrations, the reagent increased both the ATPase activity of the particles and the passive proton transport rate through the membrane. The presence of oligomycin reduced the extent of the 2-Hydroxy-5-nitrobenzyl bromide action on the proton conductivity suggesting that it acted primarily on the H+ ATPase complex. Similar effects were observed on F1-depleted particles, whilst no effect was observed on the isolated F1-ATPase activity. The results suggest that polypeptides bearing tryptophan residues may be involved in the gating function of proton channels of the mitochondrial membrane and this is particularly evident for the F0F1-ATPase complex. PMID- 2901261 TI - A new method for the isolation of fresh hepatocytes from periportal and pericentral regions of the liver lobule. AB - A simple method which avoids the use of perfusion with calcium free buffer, hydrolytic enzymes and detergents has been developed to obtain fresh hepatocytes from periportal and pericentral regions of the liver lobule. Cylindrical plugs (200 x 500 microns) of periportal and pericentral areas of the rat liver lobule weighing about 1 mg were collected with a micropunch from fresh or perfused liver. Ninety percent of cells were intact as assessed from trypan blue staining. Glutamine synthetase activity was detected predominantly (ca. 85%) in plugs isolated from pericentral regions indicating that this method allows selective harvesting of pure sublobular zones of the liver lobule. Rates of oxygen uptake measured at 25 degrees C by plugs from livers perfused in the anterograde direction were 56 +/- 5 and 33 +/- 7 mumol/g/h by periportal and pericentral plugs, respectively, values similar to data obtained from the intact organ. This method provides new opportunities to study the regulation of basic metabolic processes in cells from sublobular areas under nearly physiological conditions. PMID- 2901262 TI - Resolution and pharmacological properties of the enantiomers of the potent alpha adrenoceptor antagonist 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy phenyl)piperazine. AB - Resolution of the optical isomers of the alpha-adrenoceptor antagonist IP-66 (1 [2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl)piperazine) and its intermediate IP-30 (1-[2-hydroxy-2-(3'-pyridyl)ethyl]-4- (2'-methoxy phenyl)piperazine have been carried out. Optical purity was assayed by high pressure liquid chromatography. The antagonistic potencies of racemic mixtures and stereoisomers toward phenylephrine- and norepinephrine-induced contraction in isolated rat aortic strips have been compared. (+)-IP-66 and (+)-IP-30 were resp. 363 and 170 times more potent than respective (-) isomers in eliciting competitive alpha 1-adrenoceptor blockade. Similarly IP-66 (+) or (+/-) were extremely more effective than the (-) isomer in antagonizing norepinephrine induced pressor responses in pithed rat. PMID- 2901263 TI - Analytical profile of the new diuretic beta-blocking agent tienoxolol hydrochloride. AB - Physicochemical properties, i.e. elemental analysis, spectra (NMR, MS, IR, UV), solubilities, pKa, partition coefficient, melting point, HPLC, and data on purity and stability of ethyl 2-(3-[(1,1-dimethylethyl)amino]-2-hydroxy-propoxy)-5-[(2- thienylcarbonyl)amino]benzoate hydrochloride (tienoxolol), a new drug with antihypertensive properties are reported. PMID- 2901264 TI - Effects of moderate drinking and alcohol abstinence on urinary dolichol levels. AB - Urinary dolichols were studied during a period of 10 days of moderate drinking (60 g of alcohol daily), preceded and followed by a period of abstinence, in 10 healthy volunteers. No significant changes were observed in dolichol levels during this time. Thus, moderate alcohol consumption does not affect urinary dolichols. Furthermore, to establish the time of abstinence needed for elevated urinary dolichol levels to return to normal, 17 alcoholic patients entering a detoxification unit and with initially increased urinary dolichols, were followed for seven days. Mean urinary dolichol level, which was clearly elevated in the beginning of detoxification, returned to normal by the 5th day of the treatment. Half-life decay for increased urinary dolichols was found to be about 3 days. PMID- 2901265 TI - Transdermal beta-blocker therapy in essential hypertension. AB - Transdermal drug delivery has been applied to various agents in an effort to decrease the frequency of drug administration and increase the patients compliance. In our study, we demonstrated that transdermal application of a beta blocker (20 mg mepindolol) in patients with essential hypertension led to effective blood pressure lowering effect within 1 week (160.1 +/- 6.1 mm Hg/95.8 +/- 8.3 mm Hg vs 136.8 +/- 7.2 mm Hg/84.3 +/- 5.0 mm Hg; P less than 0.05). A controlled study of transdermal versus oral beta-blocker administration in hypertensives is necessary before this new therapeutic system is introduced in antihypertensive treatment. PMID- 2901267 TI - Terazosin, a new selective alpha 1-adrenergic blocking agent. Results of long term treatment in patients with essential hypertension. AB - The long-term treatment of essential hypertension with terazosin, a new once-a day alpha 1-adrenergic blocking agent, was evaluated in 364 hypertensive patients who received total daily doses of 1 to 40 mg for 3 weeks to 56 months. Consistent mean decreases in supine and standing systolic and diastolic blood pressures were observed throughout the study for patients treated with terazosin as monotherapy (supine, 9 to 12/10 to 13 mm Hg; and standing, 12 to 18/11 to 14 mm Hg) or in combination with other antihypertensive agents (supine, 12 to 16/12 to 15 mm Hg; and standing, 16 to 22/13 to 19 mm Hg). The most commonly reported adverse experiences were dizziness, headache, asthenia, cold symptoms, and nasal congestion. Adverse effects and metabolic disorders often associated with diuretics and beta blockers such as sexual dysfunction, hyperglycemia, hyperuricemia, hypokalemia, or adverse lipid effects were seen infrequently during long-term treatment with terazosin as monotherapy. Overall, terazosin was shown to be effective, safe, and well tolerated by most patients. PMID- 2901266 TI - Comparison of betaxolol, a new beta 1-adrenergic antagonist, to propranolol in the treatment of mild to moderate hypertension. AB - A double-blind, multicenter study compared the safety and efficacy of oral betaxolol 10 to 40 mg once daily (n = 68) with propranolol 40 to 160 mg twice daily (n = 73) in the treatment of mild to moderate essential hypertension. Both agents produced significant (P less than 0.01) and comparable reductions in mean supine systolic and diastolic blood pressures (7/11 mm Hg on betaxolol and 9/10 mm Hg on propranolol). Both betaxolol and propranolol significantly (P less than 0.01) reduced mean supine heart rate by 9 beats per minute. Patients achieved a more significant (P less than 0.01) reduction in blood pressure earlier (weeks 2 and 4 of the titration period) with betaxolol. By the end of treatment there was no significant difference in response between treatment groups. A higher incidence of central nervous system side effects (insomnia, bizarre dreams, depression, hallucinations, dizziness), however, was seen with propranolol than with betaxolol. Overall, the data show that in patients with mild to moderate essential hypertension, betaxolol 10 to 40 mg administered once daily is as effective as and better tolerated than propranolol 40 to 160 mg administered twice daily. PMID- 2901269 TI - Ontogeny of blood pressure in the inbred Dahl hypertension-sensitive and resistant rat. AB - The inbred S/JR rat is characterized by a genetic predisposition to NaCl-induced hypertension. Although mature S/JR but not R/JR rats develop hypertension when fed a high NaCl-containing diet, this effect has not been examined during early neonatal development. S/JR and R/JR dams were maintained on 0.15% (w/w) or 8% (w/w) NaCl diets throughout gestation and lactation. Measurements of mean abdominal aortic blood pressure (MAP) were obtained in anesthetized offspring at 5, 15, and 25 days of age. This was greater in neonatal S/JR rats than R/JR rats at 5, 15, and 25 days of age. A hypertensinogenic effect of 8% NaCl was seen in R/JR at 5 and 15 days. The results indicate that the ontogeny of MAP can be influenced by pre- and postnatal dietary NaCl. More importantly, elevated MAP in the S/JR strain is a distinguishing characteristic evident throughout the neonatal period of development. PMID- 2901268 TI - Effects of beta-blockade on muscle metabolism during prolonged exercise. A short review. AB - Endurance during prolonged exercise decreases more markedly with nonselective than beta 1-selective beta-blockade. Because both types of blockers exert comparable effects on cardiac performance, oxygen supply to the working muscle, and extramuscular substrate mobilization, the difference in exercise capacity is apparently due to other factors. The available information in the literature along with experimental results from our laboratory suggests that inhibition of intramuscular lipolysis only occurs with nonselective beta-blockade and may partly account for this difference. In addition, alterations in potassium fluxes are particularly induced by nonselective beta-blockade and result in more pronounced decreases in the intracellular-extracellular potassium ratio during exercise than caused by placebo or beta 1-selective blockade. In contrast to what was initially proposed, intramuscular glycogenolysis appears not to be affected by either type of beta-blockade, and a decrease is unlikely to be involved in the reduced exercise capacity. PMID- 2901270 TI - Comparison of large dose of vecuronium with pancuronium for prolonged neuromuscular blockade. AB - Dose-duration relationships for vecuronium were determined and the duration of action produced by vecuronium 0.3 mg kg-1 shown to equal that of pancuronium 0.1 mg kg-1. Using these doses, the neuromuscular blocking properties and cardiovascular effects of the two drugs were compared. With large dose administration of vecuronium (0.3 mg kg-1), both the onset time (mean 81 s) and the 25-75% recovery index (mean 13.9 min) were about one-half those associated with pancuronium (mean 168.5 s and 29.3 min, respectively). The duration of action until 25% recovery was similar with both drugs. There was no evidence of cardiovascular instability with the large dose of vecuronium. Heart rate, however, was significantly slower (range 89.7-94.2% of control) 2-20 min after the injection of vecuronium. Vecuronium 0.3 mg kg-1 may have more favourable neuromuscular blocking effects than pancuronium 0.1 mg kg-1 and may be preferable to pancuronium when prolonged neuromuscular blockade is required. PMID- 2901271 TI - Bradycardia following vecuronium. PMID- 2901273 TI - Partial purification of the sodium- and potassium-coupled L-glutamate transport glycoprotein from rat brain. AB - The sodium- and potassium-coupled L-glutamate transporter from rat brain has been solubilized with cholate and 10-20-fold purified using Wheat Germ Agglutinin Sepharose 4B. Transport activity--as determined upon reconstitution of the fraction into liposomes--was retained on the column and eluted by N acetylglucosamine. When the glycoprotein fraction was depleted of the N acetylglucosamine and applied to a second round of lectin-chromatography, the L glutamate transport activity was retained and again could be eluted by the sugar. The transporter activity reconstituted from the glycoprotein fraction exhibited the same features as that in synaptic plasma membranes, including electrogenicity, an absolute dependence on external sodium and internal potassium, affinity and stereospecificity. Furthermore, efflux and exchange properties of the reconstituted preparation were also unchanged by the solubilisation and lectin-chromatography. These observations indicate that the sodium- and potassium-coupled L-glutamate transporter is a glycoprotein and is predominantly reconstituted in the 'right-side-out' conformation. PMID- 2901272 TI - Conversion of coupling factor 1 of Rhodospirillum rubrum from a Ca2+-ATPase into a Mg2+-ATPase. AB - Isolation of F1-ATPase from Rhodospirillum rubrum by chloroform extraction of chromatophores, followed by purification on a glycerol gradient, results in a very pure enzyme preparation containing five subunits with high Ca2+-ATPase activity (15 mumol per min per mg protein). Furthermore, conditions are reported under which the purified F1 exhibits Mg2+-dependent ATPase activity of about 35 mumol per min per mg protein. NaHCO3 stimulates the Mg2+-activity from 1.5 mumol per min per mg protein to 5 mumol per min per mg protein giving a maximal activity at a concentration of about 60 mM NaHCO3. Lauryl dimethylamine oxide (LDAO), octyl glucoside and nonanoyl N-methylglucamide enhance the Mg2+-ATPase activity from 1.5 to 14, 22 and 35 mumol per min per mg protein, respectively, in the absence of NaHCO3, and from 5 to 34, 30 and 37 mumol per min per mg protein, respectively, in the presence of 50 mM NaHCO3. The Vmax is increased, but the Km for ATP remains the same, about 0.22 mM, both in the absence of activators and in the presence of NaHCO3, LDAO or NaHCO3 plus LDAO. Ca2+-dependent ATPase activity is slightly stimulated by NaHCO3 but strongly inhibited by octyl glucoside. PMID- 2901274 TI - Lyophilized Clostridium perfringens 3 alpha- and Clostridium bifermentans 7 alpha hydroxysteroid dehydrogenases: two new stable enzyme preparations for routine bile acid analysis. AB - Preparations of 3 alpha-hydroxysteroid dehydrogenase (EC 1.1.1.50) from Clostridium perfringens were successfully lyophilized into a stable powder form. Purification of the enzyme was achieved using triazine dye affinity chromatography. C. perfringens 3 alpha-hydroxysteroid dehydrogenase was purified 24-fold using Reactive Red 120 (Procion Red) -cross-linked agarose (70% yield). Quantitative measurement of bile acids with the purified enzymes, 3 alpha hydroxysteroid dehydrogenase and 7 alpha-hydroxysteroid dehydrogenase (EC 1.1.1.159) from Clostridium bifermentans (strain F-6), was achieved spectrophotometrically. Standard curves with chenodeoxycholic acid (CDC) and cholic acid were linear within a concentration range of 20-100 microM. Analysis of mixtures of ursodeoxycholic acid and CDC showed the additive nature of the 3 alpha-hydroxysteroid dehydrogenase and showed also that 7 alpha-hydroxyl groups were independently quantified by the 7 alpha-hydroxysteroid dehydrogenase. Bile acids in Folch extracts of human bile samples were measured using purified preparations of Pseudomonas testosteroni 3 alpha-hydroxysteroid dehydrogenase, C. perfringens 3 alpha-hydroxysteroid dehydrogenase, Escherichia coli 7 alpha hydroxysteroid dehydrogenase and C. bifermentans (strain F-6) 7 alpha hydroxysteroid dehydrogenase. Statistical comparison validated the use of C. perfringens 3 alpha- and C. bifermentans 7 alpha-hydroxysteroid dehydrogenases for the quantification of bile acids in bile. PMID- 2901275 TI - b-chains prevent the proteolytic inactivation of the a-chains of plasma factor XIII. AB - While the transglutaminase activity is associated exclusively with the thrombin cleaved a chains of plasma Factor XIII, there is little information regarding the role of the b-chains. The present investigations were undertaken to clarify the role of the b-chains during proteolytic activation of plasma factor XIII a chains. The a-chains of platelet Factor XIII (a2) were extremely sensitive to alpha-thrombin proteolysis, especially in the presence of 5 mM EDTA, resulting in two major fragments with molecular masses 51 +/- 3 kDa and 19 +/- 4 kDa. Furthermore, fibrin enhanced the alpha-thrombin proteolysis of thrombin-cleaved platelet Factor XIII a-chains in presence of CaCl2 or EDTA, resulting in several peptide fragments with molecular masses from 51 +/- 3 kDa to 14 +/- 4 kDa. By contrast, thrombin-cleaved a-chains of plasma Factor XIII (a2b2) were not further degraded by alpha-thrombin in presence of 5 mM EDTA. Even in the combined presence of 5 mM EDTA and 0.1 mg/ml fibrin, alpha-thrombin proteolysis of plasma Factor XIIIa was limited to the formation of a 76 kDa fragment (= Factor XIIIa), a 51 +/- 3 kDa fragment and trace amounts of a 14 +/- 4 kDa species. Platelet Factor XIII proteolyzed by 500 nM alpha-thrombin in presence of 5 mM EDTA expressed less than 20% of enzymatic activity obtained when platelet Factor XIII was activated in presence of 5 mM CaCl2. In contrast, plasma Factor XIII activated by 500 nM apha-thrombin in presence of 5 mM EDTA expressed nearly 65% of original transglutaminase activity. Likewise, when plasma Factor XIII was proteolyzed by 100-1000 nM gamma-thrombin in presence of 5 mM CaCl2 or 5 mM EDTA, maximal transglutaminase activity was observed. However, when platelet Factor XIII was similarly treated with gamma-thrombin in presence of 5 mM EDTA, only one half the original transglutaminase activity was obtained. The b-chains thus appear to mimic the function of Ca2+ in preserving transglutaminase activity of thrombin-cleaved a-chains. The b-chains of plasma Factor XIII were not degraded by either alpha- or gamma-thrombin treatment, in presence of 5 mM EDTA or 5 mM CaCl2. Both platelet and plasma Factor XIII a-chains were degraded by trypsin to fragments with molecular masses of 51 +/- 3 kDa and 19 +/- 4 kDa in presence of 5 mM CaCl2 and to fragments with molecular masses of 19 +/- 4 kDa and lower, in presence of 5 mM EDTA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2901276 TI - Adverse effects of drugs on the immature kidney. AB - The immature kidney may be adversely affected by a variety of vasoactive or diuretic drugs, either administered to the mother during pregnancy, or to the neonate. Inhibitors of the angiotensin-converting enzyme administered to the hypertensive pregnant woman can severely and sometimes definitely impair renal function in the fetus, leading to postnatal anuria. Pathogenesis involves interference with the renin-angiotensin system and the prostaglandins. Beta adrenergic agents administered during labor depress glomerular filtration rate transiently. Tolazoline, an alpha-adrenergic blocking agent useful in the treatment of persistent pulmonary hypertension of the neonate induces intense renal vasoconstriction with consequent hypoperfusion. Indomethacin, a prostaglandin synthetase inhibitor used for the pharmacological closure of a patent ductus arteriosus, also increases renal vascular resistance, and decreases urine output. Furosemide, the drug most often used in oliguric neonates, may also adversely affect the newborn infant. Its use has been associated with an increase in the incidence of patent ductus arteriosus, hypercalciuria, nephrocalcinosis and secondary hyperparathyroidism. These observations demonstrate that the proper use of drugs requires that the therapeutic endpoint be clearly defined and the predictable side effects be anticipated. PMID- 2901277 TI - [Comparative study of the relative hydrophobicity and interaction with striatal dopamine receptors in the bull of representative dialkylaminoalkyl and dialkylaminoacyl phenothiazine derivatives]. AB - Physicochemical properties and ability of some dialkylaminoalkyl (DAL) and dialkylaminoacyl (DAC) phenothiazine derivatives to interact with bovine striatal dopamine receptors have been investigated. DAC analogs were significantly less effective for the inhibition of [3H]-spiperone-specific binding to D2-receptors. The decrease in lipophilicity observed in DAC agents, as compared to DAL, may be one of the causes for the loss of affinity to these receptors. PMID- 2901278 TI - [Decreased ethanol consumption by rats as affected by central alpha adrenoblockaders: the role of liver aldehyde dehydrogenase isoenzymes]. AB - It has been shown in the experiments on rats that subcutaneous administration of central alpha-adrenoblockers IEM-611 (30 mg/kg and 15 mg/kg) and phenoxybenzamine (10 mg/kg) for one or two weeks brings about a decrease in voluntary ethanol consumption at early stages of experimental alcoholism (3-week alcoholization). In rats with chronic alcoholization for 6 months only IEM-611 had a remarkable inhibitory effect on alcohol consumption. Moreover, it has been stated that IEM 611 reduced threefold the activity of liver aldehyde dehydrogenase (AlDH) by the inhibition of AlDH isoenzymes with low and high Km for acetaldehyde. Phenoxybenzamine inhibited slightly only low Km AlDH. It is suggested that differences in IEM-611 and phenoxybenzamine effects may be associated with specific drug inhibition of AlDH isoenzymes. PMID- 2901279 TI - [Structural bases of the induction of immune reactions in emotional stress]. AB - Immobilization stress in rats can provoke damages of the brain parenchymal vessels, which are most pronounced in the reticular formation of the midbrain. In this case the blood plasma and cells enter the brain and the blood elements of brain tissue enter the circulation. Some experimental animals exhibit the serum complement-fixing brain antibodies and specific reactions of basophils to brain antigens 14 days after exposure to stress. Most of the rats reveal immune reactions and neurosensitivity a month later. Some of them exhibit the autoantibodies to norepinephrine and serotonin. It is suggested that stress induced brain vascular damages may play an important role in the mechanisms of immune reaction induction. PMID- 2901280 TI - 2-Chlorodeoxyadenosine: an effective new agent for the treatment of chronic lymphocytic leukemia. AB - 2-Chlorodeoxyadenosine, a new lymphocyte-selective, anti-neoplastic drug was administered to 18 patients with advanced chronic lymphocytic leukemia of B-cell origin. All patients were resistant to conventional treatment. A total of 44 courses of 2-chlorodeoxyadenosine were completed with minimal toxicity. An overall response rate of 55% was achieved with four of 18 patients demonstrating partial response and six of 18 patients experiencing clinical improvement. Only minor bone marrow suppression occurred during administration of the drug, indicating a high degree of lymphocyte selectivity. Reduction of lymphocyte infiltration in bone marrow occurred in treated patients including one patient who experienced normalization of the bone marrow. Three of four patients with concurrent autoimmune hemolytic anemia experienced resolution of hemolysis, as indicated by elimination of transfusion requirement, fall in reticulocyte count, elevation of hemoglobin, and ability to taper prednisone without recurrence of hemolysis. Duration of responses ranged from 2 to 15 months without maintenance therapy. PMID- 2901281 TI - Treatment of pancreatic fistula with the somatostatin analogue SMS 201-995. PMID- 2901282 TI - Evidence that activation of in vitro hippocampal theta rhythm only involves muscarinic receptors. AB - The present study was conducted for two purposes: the first was to evaluate whether activation of nicotinic receptors in the hippocampal formation in vitro (slice) preparation was capable of producing type 2 (atropine-sensitive) theta rhythm. The cholinergic nature and involvement of muscarinic receptors in this type of theta has been previously well documented. The second purpose was to determine whether perfusion of a number of (other) putative neurotransmitters shown to be present in the hippocampal formation could elicit type 1 (atropine resistant) theta in the slice preparation. Further experiments were conducted to determine if these agents interacted in any manner with cholinergically-induced type 2 theta. Electroencephalic (EEG) theta activity was not induced by nicotine, providing evidence for an exclusive muscarinic receptor involvement in this cholinergically-induced type 2 theta. In addition, theta activity was not elicited by the application of gamma-aminobutyric acid (GABA), glutamate, norepinephrine, dopamine or serotonin. The application of any of these agents did not significantly alter the production of cholinergically-induced theta. These results suggest that type 1 theta originates in regions extrinsic to the hippocampus, or is the result of the interaction of several neurotransmitters on different receptors. PMID- 2901284 TI - Comparison of two groups of tardive dyskinesia patients--antipsychotic medication reduced vs unchanged. PMID- 2901283 TI - Kindling does not cause persistent changes in firing rates or transmitter sensitivities of substantia nigra pars reticulata neurons. AB - These studies were undertaken to determine whether the kindling process induces persistent alterations in the functional status of neurons of the substantia nigra pars reticulata, a brain area identified previously as a site important in regulating the expression of generalized motor seizures. Extracellular, single unit recordings of pars reticulata neurons were made in chloral hydrate anesthetized, fully kindled rats (2-3 weeks after the last seizure), or unkindled control rats of the same age and weight. Kindling caused no alterations in several electrophysiological parameters examined. For instance, neither the number of active pars reticulata cells encountered, nor their firing rates, were significantly different between kindled and control groups. In addition, kindling failed to alter the sensitivities of pars reticulata neurons to iontophoretic application of two inhibitory transmitters, gamma-aminobutyric acid and glycine, and two transmitters that excite these cells, glutamate and acetylcholine. These results suggest that while kindling produces enduring increases in seizure susceptibility, it causes no persistent interictal changes in either basal activity or several measures of transmitter sensitivity of substantia nigra pars reticulata neurons. PMID- 2901285 TI - Effect of hormones on hydrolase activities and DNA synthesis in kidney of the developing mouse. AB - The postnatal development of brush border enzyme activities, namely maltase, trehalase, alkaline phosphatase, gamma-glutamyltranspeptidase, and leucylnaphthylamidase, as well as the ontogenic profile of DNA synthesis has been determined in the mouse kidney. In addition, these parameters were evaluated following daily administration of hormones during 3 days to 8-day-old mice. Insulin or epidermal growth factor induced a 34% increase of maltase activity over that of 11-day-old controls. Trehalase activity was precociously and significantly augmented by cortisone alone or combined with thyroxine (p less than 0.05), although thyroxine alone had no influence. Only epidermal growth factor had a significant effect on alkaline phosphatase activity. gamma Glutamyltranspeptidase activity was significantly decreased when insulin and thyroxine were given simultaneously, but was not modified by any of the hormones injected separately. The level of leucylnaphthylamidase activity was enhanced by 70% after cortisone injection, but it was significantly reduced by thyroxine injected in combination with insulin or cortisone. The incorporation of [3H]thymidine into DNA was increased by 107% after epidermal growth factor administration, but it was decreased by 33% after the cortisone treatment. In spite of this precocious reduction, the level of incorporation was still 2 times higher than that in adult mice. These results show that hormones act separately or in cooperation to accelerate or retard the maturation of the suckling mouse kidney. PMID- 2901286 TI - The action of agonists and antagonists at the histamine H1 receptor and receptor protection studies in guinea pig ileum. AB - We have examined the ability of histamine and the competitive reversible antihistamines to protect the histamine H1 receptor against alkylation with the 2 haloalkylamines, phenoxybenzamine and SY-14. In isolated guinea pig ileum these irreversible antagonists produce a parallel shift in the dose-response curve to histamine with retention of the maximum response if they are used at concentrations less than about 10(-6)M. Treatment with these 2-haloalkylamines in the presence of a high concentration of histamine did not alter the blocking activity. Thus histamine appears to be unable to protect its own receptor against irreversible blockade. The competitive reversible antagonists, on the other hand, did provide effective protection against irreversible blockade. It is likely that the competitive reversible H1 receptor antagonists have at least some part of their attachment site in common with irreversible antagonists of the 2 haloalkylamine type, while the inability of histamine to provide self-protection suggests that its primary attachment site is different from that of the antagonists. PMID- 2901287 TI - Restriction fragment length polymorphism and multiple copies of DNA sequences homologous with probes for P-fimbriae and hemolysin genes among uropathogenic Escherichia coli. AB - Hemolysin and P-fimbriae are two virulence traits frequently found together in uropathogenic Escherichia coli. Previous studies have discovered evidence both for linkage between the genes for these traits and for their duplication in the chromosomes of a limited number of strains. To test whether these observations are characteristic of uropathogenic Escherichia coli, the method of DNA hybridization to DNA restriction fragments separated by electrophoresis and transferred to nylon was used to determine copy number of genes for P-fimbriae (pap) among 51 E. coli strains isolated from symptomatic urinary tract infections. Twenty percent of the strains had more than one copy of pap homologous sequences. Fifteen strains, each representing a unique clone, were examined for the presence of sequences homologous with cloned hemolysin genes (hly). Samples of DNA from 14 of the 15 strains hybridized with hly probes. In eight strains the number of copies of pap equalled the number of copies of hly, including one strain with two apparent copies of each. Five strains appeared to have one more copy of pap than of hly, and one strain had an extra copy of hly. PMID- 2901288 TI - Clonal genomic alterations in glioma malignancy stages. AB - Comparison of constitutional and tumor genotypes at chromosomal loci defined by restriction fragment length alleles has proven useful in determining the genomic position and tissue specificity of recessive mutations that predispose to cancer (Hansen, M.F., and Cavenee, W.K. Cancer Res., 47:5518-5527, 1987). Here we have applied this approach to 53 unrelated patients with glial tumors of varying histological malignancy grade. Loss of constitutional heterozygosity for loci on chromosome 10 was observed in 28 of 29 tumors histologically classified as glioblastoma (malignancy grade IV) whereas no similar losses were observed in any of 22 gliomas of lower malignancy grade. Examination of restriction fragment length alleles on other chromosomes revealed that loss of sequences on chromosomes 13, 17, or 22 had occurred at nonrandom frequencies and in at least one instance of each malignancy grade of adult glioma. The tumors in which loss of constitutional heterozygosity was observed were composed of one or a mixture of glial cell subtypes displaying astrocytic, oligodendrocytic, and/or ependymal differentiation. These results demonstrate a close association of the loss of chromosome 10 sequences with the most malignant histological stage of glioma and that glioblastoma arises as the clonal expansion of an earlier staged precursor. Furthermore they suggest that glioblastoma is a common phenotypic and malignancy terminus for glial tumors of various cellular subtypes which is reached through a common molecular pathway. This approach which involves the identification of malignancy stage specific somatic losses of heterozygosity provides a genotypic, rather than phenotypic, analysis of tumor progression. PMID- 2901289 TI - Predicting return to work after acute myocardial infarction. Significance of clinical data, exercise test variables and beta-blocker therapy. AB - Among 66 full-time employed men surviving an acute myocardial infarction (AMI) and participating in the Norwegian postinfarction study with timolol, 50 (75.7%) resumed their previous work within 12 months, and 16 (24.3%) retired. Stepwise logistic regression analysis of clinical data and of results from an exercise test 3 months post AMI revealed the following factors of independent predictive value for enhanced return to work: previous labor characterized as light or moderately heavy (p = 0.001), low age at the time of infarction (p = 0.001), timolol treatment (p = 0.009), ability to stop smoking post AMI (p = 0.006), and a high exercise capacity on the exercise test (p = 0.016). It is concluded that the clinical history and an exercise test 3 months after AMI can identify patients who are more likely to resume work, and that post-AMI beta-blocker treatment with timolol and ability to stop smoking are predictive of an enhanced return to work. PMID- 2901290 TI - Enterochromaffin (EC-) cells of the mammalian gastro-entero-pancreatic (GEP) endocrine system: cellular source of pro-dynorphin-derived peptides. AB - It has long been disputed whether mammalian enterochromaffin (EC-) cells contain a peptide in addition to serotonin. Previous immunohistochemical studies have provided evidence for the presence of enkephalins in EC-cells. These findings, however, are equivocal. Therefore, the problem of opioid peptides in EC-cells has been re-examined in the gastro-intestinal mucosa of dog, guinea-pig and man. A battery of antisera against derivatives of pro-opiomelanocortin, pro-enkephalin and pro-dynorphin have been applied to semithin serial sections of the tissues, in combination with fluorescence histochemistry and serotonin immunocytochemistry. Our findings indicate that EC-cells of the investigated species contain pro-dynorphin-related peptides, i.e. dynorphin A and alpha-neo endorphin, but no derivatives from pro-opiomelanocortin or pro-enkephalin. Since remarkable interspecies variations occur with respect to the number and staining characteristics of opioid immunoreactive EC-cells, it is concluded that pro dynorphin shows specific routes of post-translational processing depending upon the species and the gastro-intestinal segment investigated. Future studies should focus on the mutual relationships between serotonin and dynorphins and on the physiological significance of these peptides in the gastrointestinal tract. PMID- 2901292 TI - Ectopic expression of Thy-1 in the kidneys of transgenic mice induces functional and proliferative abnormalities. PMID- 2901291 TI - Selective decrease of immunoreactive tyrosine hydroxylase in nigrostriatum of adult male rats after N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment. AB - Several laboratories have reported that N-methyl-4-phenyl-1,2,3,6 tetrahydropyridine causes damage to the nigral dopamine neurons of man, monkey, and mouse. Controversial data suggest that a rat model of Parkinsonism may be possible. Although loss of dopamine cells has not been detected in the rat brain, our immunocytochemical studies show that immunoreactive tyrosine hydroxylase, the rate-limiting enzyme which synthesizes dopamine, is significantly reduced in concentration, or its antigenicity altered, in substantia nigra/pars compacta as well as the caudate nucleus. Optical density measurements demonstrate the reduction or alteration of immunoreactive tyrosine hydroxylase in nigro-striatal neurons, indicating that axonal terminals, as well as parent perikarya, may be sensitive to the drug. After treatment, abnormal morphological remodelling may result in the affected neuronal processes, perhaps indicating sublethal toxicity, followed by slow recovery. Despite the lack of nigral cell death, it is proposed that the present data support the use of the rat as a model to investigate the early effects of Parkinsonism induced by this agent, and the biological mechanisms of cellular recovery. PMID- 2901293 TI - A role in transmembrane signaling for the cytoplasmic domain of the CD2 T lymphocyte surface antigen. AB - The CD2 antigen can mediate mitogenesis of T lymphocytes after binding combinations of monoclonal antibodies. To examine the importance of the cytoplasmic domain in signaling, rat CD2 cDNA has been transfected into the human Jurkat cell line and triggering of an increase in cytoplasmic free Ca2+ concentration [( Ca2+]i) has been assayed. In cells expressing full-length CD2, a clear signal was triggered with anti-CD2 monoclonal antibodies. In contrast, a barely detectable increase in [Ca2+]i occurred with mutant rat CD2 molecules that included only 6 or 40 amino acids of the full-length cytoplasmic domain of 116 residues. It thus appears that the CD2 cytoplasmic domain plays a role in the signaling event. PMID- 2901294 TI - The pharmacology and biochemical action of second-line agents. PMID- 2901296 TI - Syntheses of the optical isomers of befunolol.HCl and their beta-adrenergic blocking activities. PMID- 2901295 TI - The oliC3 gene of Aspergillus niger: isolation, sequence and use as a selectable marker for transformation. AB - The oliC3 gene of Aspergillus niger has been isolated and sequenced. This gene encodes an oligomycin-resistant variant of the mitochondrial ATP synthase subunit 9. In transformation experiments the gene can serve as a semi-dominant selectable marker for A. niger. It was possible to recognize transformants in which oliC3 had integrated at the homologous oliC locus, as opposed to elsewhere in the genome, by observation of phenotypes on medium containing oligomycin. DNA sequencing has allowed comparison of the deduced amino acid sequence with subunit 9 proteins from other species and comparison of 5' untranslated sequences with those from other fungi. PMID- 2901297 TI - [The concept of tropical neuromyelopathy]. AB - Since the beginning of this century, the concept of tropical neuromyelopathy (T. N. M.) was progressively elaborated in tropical areas. This disorder is constituted by three main clinical syndromes (e.g.: polyneuropathy, spastic paraplegia, ataxia). Abnormal clinical, electrophysiological and pathological features, observed in all clinical forms argue in favor of a diffuse pathobiological process of the nervous system. The association with positive HTLV 1 serology, has recently induced a great interest for the spastic forms of T. N. M. Tropical spastic paraplegia tend to be individualized. This attitude differs from the global concept of T. N. M. which allows gathering similar clinical syndromes. This T. N. M. group should be kept intact until the discovery of new etiologies. Toxic (manioc, lathyrism) or deficiency (hypovitaminosis, malabsorption) causes are incriminated. Otherwise etiologies are unknown. PMID- 2901298 TI - Analysis of idiotypic and anti-idiotypic antibodies as models of receptor and ligand. AB - Antibodies to small bioactive ligands and peptides may mimic the binding characteristics of the natural receptor; in turn, the anti-idiotypic antibodies generated against the binding sites of such anti-ligand antibodies may mimic some aspects of small bioactive ligands and peptides. Among the several levels of investigation of such antibody-receptor networks are (a) the quantitative structure-activity relationships of ligand binding to antibody as compared with natural receptor; (b) the molecular modeling of antibody-receptor binding sites and the genomic basis for such structures; and (c) the characteristics of the molecular mimicry exhibited by "mimetopes" on anti-idiotypic antibodies. To illustrate the analysis encountered at each of these levels, we discuss here antibody and anti-idiotypic systems that are directed to small neuroactive ligands and their receptors. PMID- 2901299 TI - Liver-function studies in heart-transplant recipients treated with cyclosporin A. AB - Cyclosporine (CsA) hepatotoxicity has been reported but has not been studied systematically. This study includes 17 patients undergoing heart transplantation (HTx) and being treated with CsA, azathioprine, and corticosteroids. We assessed liver function in these patients before HTx and during the following month by five biological tests: total bile acids (BA), alkaline phosphatase (AP), gamma glutamyltransferase (GGT), and total bilirubin in serum, and the aminopyrine breath test (ABT). With these tests we could classify the patients into three groups before HTx: normal (group I), mildly altered (group II), and severely altered (group III) liver function. During CsA therapy we did not observe any changes in any test results except for BA and GGT, and these only in group III. The ABT improved significantly in this group. During kinetic studies in patients without liver dysfunction, we confirmed a direct interference of CsA on BA secretion mechanism, but not the GGT increase, which remains to be explained. PMID- 2901300 TI - Plasma amino acid pattern of patients with HIV infection. AB - We measured the free amino acids in plasma of 58 patients with HIV infection and in six persons in the risk group. The HIV+ patients had significantly increased concentrations of arginine, phenylalanine, and glutamate in comparison with both age- and sex-matched controls and the members of the risk group. Glutamate concentrations increased only in an advanced stage of the disease (WR 5 and 6 of the Walter Reed staging classification), whereas arginine and phenylalanine increased independently of the stage. There was no correlation between the amino acid concentrations and the number of T4 and T8 lymphocytes, the sedimentation rate, and the existence or absence of Kaposi's sarcoma. The amino acid pattern of HIV-infected persons is similar to that of cancer patients or those with other immune deficiencies. PMID- 2901301 TI - Growth hormone releasing factor stimulates and somatostatin inhibits prolactin release from human mixed somatotroph-lactotroph adenomas in perifusion. AB - The effects of human growth hormone-releasing factor (hGRF) and somatostatin on growth hormone (GH) and prolactin (PRL) secretion in perifusion of dispersed cells of human GH-secreting adenomas, obtained from seven acromegalic patients with hyperprolactinaemia, were examined. Six adenomas stained for both GH and PRL on immunohistochemical examination, and one contained only GH. GH release was consistently stimulated in a dose-dependent manner by hGRF (0.01, 0.1 and 1.0 nM) in all seven adenomas studied. PRL release was undetectable in two adenomas. In the other five, hGRF stimulated PRL release and the response was dose related. Furthermore, the PRL response was significantly correlated with the GH response to hGRF. When cells were perfused with somatostatin (1 nM), GH and PRL secretion induced by hGRF was completely antagonized. We also evaluated the effect of hGRF pretreatment on the subsequent GH response to hGRF in two adenomas. hGRF pretreatment (1 nM) for 210 min reduced the GH response to a subsequent hGRF challenge (100 nM) in one tumour but not in the other. In conclusion, the PRL response is similar to the GH response in mixed GH and PRL-secreting adenomas after exposure to GH release-stimulating and inhibiting hormones. After prolonged exposure to hGRF, some adenomas remain responsive to further stimulation with hGRF, whereas others do not. PMID- 2901302 TI - GH feedback occurs through modulation of hypothalamic somatostatin under cholinergic control: studies with pyridostigmine and GHRH. AB - We have studied the effect of increased cholinergic tone on the GH response to growth hormone-releasing hormone (GHRH) and on GH feedback, using pyridostigmine, an acetylcholinesterase inhibitor. In six healthy male adult volunteers 120 mg oral pyridostigmine increased basal GH secretion compared to placebo and augmented the GH response to 100 micrograms i.v. GHRH (1-29) NH2; the effect was more than the additive effect of pyridostigmine and GHRH when each was given alone. Pretreatment with 2 IU methionyl-hGH given i.v. abolished the serum GH response to GHRH given 3 h later, demonstrating a negative feedback loop of GH on the response to GHRH; this inhibited response to GHRH was restored in subjects given pyridostigmine as well as methionyl-hGH. The data demonstrate that enhanced cholinergic tone releases GH, augments the serum GH response to GHRH and unblocks the negative feedback effect of methionyl-hGH pretreatment on the GH response to GHRH. These results suggest that GH negative feedback effects on its own secretion occur predominantly through increased hypothalamic somatostatin secretion; this somatostatin secretion is under inhibitory cholinergic control. PMID- 2901303 TI - Sulphasalazine in rheumatoid arthritis: combination therapy with D-penicillamine or sodium aurothiomalate. AB - This open study examined the safety of adding a second slow-acting anti-rheumatic drug (SARD) - D-penicillamine or sodium aurothiomalate - to the therapy of 38 rheumatoid patients already established on sulphasalazine. Combined anti rheumatic therapy given in this way was generally well-tolerated and the incidence of adverse reactions was not increased. During the first year none of the reactions were serious although 9 of the 29 patients (31%) given D penicillamine and 3 of the 9 patients receiving aurothiomalate developed side effects requiring withdrawal of the second SARD. Reactions attributed to D penicillamine were: gastro-intestinal - 6, rashes - 2, and blurring of vision - 1. All 3 reactions occurring with gold were rashes, 2 associated with proteinuria and one with increased liver enzymes. During the second year D-penicillamine was withdrawn in 4 patients due to thrombocytopenia - 2, and rashes - 2. In addition an overall favourable clinical response was achieved in 70% of patients. This approach for combination therapy whereby a second SARD is given to patients already established on a single SARD, appears to minimise the toxicity which is a problem when 2 SARDs are started simultaneously. PMID- 2901304 TI - How reliable is ESR as a measure of disease activity in rheumatoid arthritis treated with hydroxychloroquine? AB - Forty-two patients with active rheumatoid arthritis treated with hydroxychloroquine sulphate (400 mg day-1) for six months have been compared with patients treated with D-penicillamine (n = 14), aurothiomalate (n = 13), sulphasalazine (n = 15) and chloroquine (n = 17) to compare the changes in articular index, plasma viscosity and ESR. Results indicate that while articular index and plasma viscosity show significant improvement for all treatments, the ESR fails to improve during hydroxychloroquine therapy. PMID- 2901305 TI - The use of body mass loss to estimate metabolic rate in fasting sea birds: a critical examination based on emperor penguins (Aptenodytes forsteri). AB - 1. The validity of the body mass loss (BML) method to estimate incubation and molting metabolic rate (MR) in sea birds is examined on the basis of data in emperor penguins (Aptenodytes forsteri). 2. The BML composition of emperors during mid incubation is revised (61.7% fat, 5.9% protein and 32.4% water; energy equivalent of BML = 25.5 kJ/g). 3. Using these data in short-term fasting petrels and penguins, or with BML obtained at the beginning or at the end of the fast in long-term fasting species, may lead to up to 2-fold overestimates of incubation metabolic rate (IMR). Similarly, molting MR may be overestimated by up to three times. 4. The use of the 25.5 kJ/g energy equivalent with BML obtained during middle part of the incubation shift seems valid in long-term fasting species. It is suggested that IMR within the thermoneutral zone might be close to basal MR in most antarctic and sub-antarctic sea birds. PMID- 2901306 TI - Phosphoadenylate concentrations and adenylate energy charge of largemouth bass (Micropterus salmoides): relationship with condition factor and blood cortisol. AB - 1. Concentrations of phosphoadenylate nucleotides and adenylate energy charge in the dorsal muscle and blood of largemouth bass from a reservoir receiving heated effluent were investigated. These values were compared with the length, weight, body condition and blood cortisol concentrations. 2. Body condition of the largemouth bass ranged from 1043 to 2544, reflecting the range of condition due to starvation of some fish in the population. 3. Blood cortisol concentrations ranged from 4.0 to 23.1 micrograms/100 ml with a mean of 6.3 micrograms/100 ml. 4. The adenylate energy charge of muscle (MATP) and blood ranged from 0.37 to 0.98 and 0.74 to 0.99, respectively. 5. Blood cortisol concentration was positively correlated with body condition but not correlated with the adenylate energy charge of either blood or muscle. 6. Blood cortisol concentration was negatively correlated with concentration of adenylates in both muscle and blood. PMID- 2901308 TI - Physical composition of the semen of Barbus aeneus, the smallmouth yellowfish (Cyprinidae). AB - 1. The physical composition of the semen of Barbus aeneus (smallmouth yellowfish) was determined. 2. The mean values and standard deviations for some of the physical properties were as follows: sperm count = 8.41 x 10(6)/mm3 +/- 2.55; percentage live cells = 92.5% +/- 9.92; spermatocrit = 61.9% +/- 5.74 and the total motility = 65 +/- 8.95. The colour of the sperm samples were white while the viscosity varied between 2 and 3 on the scale 1-3. PMID- 2901307 TI - Development of glucose active transport in embryonic chick intestine. Influence of thyroxine and hydrocortisone. AB - 1. Glucose active transport is detectable in 12-day-old embryonic chick duodenum and increases at least 11-fold after 4 days of postnatal life. 2. Glucose active transport develops at the in vivo rate in 72-hr cultures of 14-day embryonic duodenum. 3. In the presence of either 1 nM thyroxine or 1 microM hydrocortisone in vitro, glucose active transport reaches levels approximately 200% of control values (equivalent to 18-19 day levels in vivo). 4. Thyroxine and hydrocortisone act by different mechanisms based on their antagonistic interaction and differences in time course of action, requirement for protein synthesis and modulation by extracellular calcium. PMID- 2901309 TI - Sexual maturity and physical exercise alter fibrinolytic activity in birds (chickens). AB - 1. Sexual maturity in the domestic hen is accompanied by hyperlipidaemia. This study examined effects of hyperlipidaemia on fibrinolytic activity at rest and following prolonged treadmill exercise. 2. In immature hens the mean pooled plasma fibrinolytic activity was 50 mm2 and following 90 min continuous exercise this rose to 114 mm2. In contrast, fibrinolytic activity in mature hens was undetectable but rose to 51 mm2 after exercise. 3. The fibrinolytic response of mature and immature cocks was comparable to that of the immature hens. 4. The resting plasma triglyceride concentration in mature hens was approximately seven times that of the immature hens, immature and mature cocks. Exercise induced significant increases in plasma non-esterified fatty acid concentrations but had no significant effect on triglyceride or cholesterol levels. 5. The results demonstrate that prolonged exercise in birds, as in man, evokes hyperfibrinolysis. However, the response is impaired in mature females and this may be associated with increased blood lipid levels. PMID- 2901310 TI - Concentrations of serum cortisol, progesterone, estradiol-17 beta, cholesterol and cholesterol ester in the doe during the reproductive stadium, in the fetal serum, in the amniotic fluid and in the milk of rabbits, as well as correlations between these parameters. AB - 1. Serum progesterone, estradiol-17 beta and cortisol, as well as cholesterol and cholesterol ester concentrations in pregnant and lactating rabbits (New Zealand white hybrids, n = 9), were measured. These parameters were also studied in the amniotic fluid, the milk and the fetal serum (28-day old fetuses). 2. Serum progesterone and estradiol-17 beta were significantly enhanced during gestation, while the content of cortisol showed a marked elevation at the end of pregnancy. The concentrations of these hormones decreased before parturition. 3. Serum cholesterol and cholesterol ester concentrations markedly decreased in the second half of gestation (74 and 76%, respectively) and elevated after parturition and in the first week of lactation. PMID- 2901311 TI - Levels of calcium and soluble collagen in turkey egg shell membranes. AB - 1. This experiment examined the effect of weeks in egg production and type of housing confinement of turkey hens on calcium and soluble collagen levels in egg shell membranes; and discussion was given to their apparent relationship to gas exchange in turkey eggs. 2. The high level of acid-soluble collagen in inner and outer egg shell membranes of aging caged hens compared with the same aged floor penned hens may have a relationship with the low hatchability generally recognized in caged hens. 3. The levels of calcium found in the outer shell membrane are low and appeared to decrease with the age of the hen. 4. There were no differences over time in levels of total collagen and neutral salt-soluble collagen (newly formed collagen) found in egg shell membranes of turkey hens confined in cages or floor pens. 5. It is suggested that the acid-soluble collagen levels found in inner shell membranes may have a relationship in limiting respiratory gas exchange during latter incubation time, and thus limit embryo survival. PMID- 2901312 TI - Oxygen consumption and feeding rates of the sabellid polychaete, Myxicola infundibulum (Renier). AB - 1. Rates of respiration and feeding were measured for the sabellid polychaete, Myxicola infundibulum. 2. Basal rates of respiration were 1.5 times lower than routine rates. 3. Clearance and irrigation rates were independent of cell type when the worms were fed on monocultures of algae; however, preferential selection was seen when the algal species were offered simultaneously. 4. Calculations indicate that this species can meet its energetic needs at rather low cell densities. 5. It is suggested that these low energy requirements, coupled with the capacity for high pumping/clearing rates may be of adaptive significance in reducing competition for food resources. PMID- 2901313 TI - The effect of somatic and gonadal size on the rate of oxygen consumption in the subantarctic echinoid Abatus cordatus (Echinodermata) from Kerguelen. AB - 1. The rate of oxygen consumption of this burrowing spatangoid was measured for individuals ranging in size from 3-month old 2.5-mm long juveniles to 39-mm long adults. 2. The decrease in the rate of oxygen consumption/dry weight with increasing body size is greater among mature adults than among juveniles because the increase in aerobic tissue (primarily the test) with body size is less than the increase in anaerobic tissues (mainly the gonads). 3. The rate of oxygen consumption/ash-free dry weight decreased more slowly with increasing body size because of the increase in the level of inorganic material. 4. Replacement of the common fresh weight or dry weight specific oxygen consumption by a more synthetic value calculated from ash-free dry weight specific oxygen consumption measurements, to annulate the body-size effect, is proposed for interspecific comparison over a wide range of body size, taking into account parameters such as temperature. PMID- 2901314 TI - Seasonal energetics of opossums (Didelphis virginiana) in Ohio. AB - 1. Female opossums acclimatized to each of the four seasons were not significantly different (P greater than 0.05) in oxygen consumption at a Ta of 0 degrees C; the overall average was 0.66 +/- 0.1 ml O2/g-hr. 2. Body weight decreased by 27% from autumn to spring; pelage density increased in winter, but thermal conductance changed very little between seasons. 3. Respirometry revealed no evidence of thermoregulatory adjustments in opossums acclimatized to winter in Ohio. PMID- 2901315 TI - Comparative effects of sugars on the hemolytic activity of Schistosoma mansoni and other hemolytic agents. AB - 1. The rate of red blood cell lysis by the hemolytic agent in adult worm homogenates of Schistosoma mansoni is slowed in the presence of added sugars (50 mM). 2. Trisaccharides were the most effective in slowing and reducing lysis. Disaccharides were more effective than monosaccharides. 3. The addition of sodium, potassium or lithium chloride salts (25 mM) stimulated hemolysis by the S. mansoni agent. 4. Hemolysins with known mechanisms were tested to determine the effects of added sugars (50 mM) or salts (25 mM). 5. The S. mansoni hemolytic agent responds to the addition of sugars and salts in a manner similar to small membrane pore formers. PMID- 2901316 TI - Comparative lactation in two species of rat-kangaroo (Marsupialia). AB - 1. Milk composition and energy content was measured in two related marsupials, Bettongia gaimardi and Potorous tridactylus. 2. Although protein content was consistently higher in bettong milk, lactational trends in both species are similar to those reported for other marsupials. 3. The faster relative growth rate of the bettong may be correlated with the increased protein and a higher milk intake. PMID- 2901317 TI - Lack of effect of rat atrial natriuretic factor (rANF) on the renal function in frogs. AB - 1. The aim of the present experiments was to examine the question whether the rat atrial natriuretic factor (rANF 1-28) could alter the fractional excretion of sodium (FENa) and other solutes in the frog (Rana esculenta). 2. Although experiments were performed throughout the year possible seasonal changes in the animals were considered in particular. 3. In all frogs, a hypotonic diuresis was induced. 4. Under these conditions in winter frogs, the control FENa was 8.8 +/- 5.8% (15) [means +/- SD (n)], and during rANF administration 7.7 +/- 6.6% (13) (NS). 5. In summer frogs, the control and experimental FENa was 5.2 +/- 2.8% (5) and 6.0 +/- 2.5% (5), respectively (NS). 6. These results show that there was no significant effect of this polypeptide on the fractional excretion of sodium in the frog. PMID- 2901318 TI - Reabsorption of inorganic sulfate in the frog kidney: saturation of transport mechanism. AB - 1. Clearance experiments were performed to study reabsorption of inorganic sulfate (SO4) in the frog kidney. 2. During stepwise elevation of the SO4 concentration in plasma by i.v. sulfate administration (SO4 titration), the absolute reabsorption of SO4 did not increase but kept constant during mild SO4 loading. 3. The maximal reabsorptive capacity for SO4 (TmSO4) was about 0.37 mumol/30 min in this species. 4. The present results do not indicate renal net secretion of SO4 in the frog. PMID- 2901319 TI - N-acetylglucosamine binding activity in extracts of adult newt skin. AB - 1. Extracts of the dermis of the adult newt, Notophthalmus viridescens, contain hemagglutination activity which is specifically inhibited by N-acetylglucosamine. 2. The activity is soluble and is associated with a doublet in sodium dodecyl sulfate polyacrylamide gels, the bands of which have relative molecular weights of 51,000 and 57,000 under both reducing and non-reducing conditions. 3. The activity requires magnesium but not calcium, cobalt, or manganese and is inhibited by barium. 4. The activity is also dependent on pH with a pH optimum between 7.0 and 7.6. PMID- 2901320 TI - Elevated intra-rumen pressure and secondary rumen contractions in sheep (Ovis aries). AB - 1. Sheep rumens were insufflated with nitrogen to 5, 10, 15, and 20 cm water pressure and sustained at each pressure for 10 min. 2. Measurements included rumen motility, reticulorumen myoelectric activity, eructation frequency and volume, changes in tracheal pressure and rumen contraction amplitude. 3. As intra rumen pressure increased, contractions designated as special secondary contractions appeared. 4. At a pressure of approximately 15 cm water, most of the special secondary contractions became regular secondaries; therefore, the special secondaries were called pro-secondary contractions. 5. Increased intra-rumen pressure was associated with respiratory distress. The recovery phase following, rumen insufflation was accompanied by hyperpnea. PMID- 2901321 TI - Long-term starvation in Xenopus laevis Daudin--II. Effects on several organs. AB - 1. The effect of starvation for 12 months on organo-somatic indices, glycogen, protein and water contents of several organs and the Na+/K+ ratio in muscle was studied in the South African clawed toad Xenopus laevis Daudin. 2. The liver- and ovary-somatic index were reduced by 30 and 70% of the initial value after 12 months. Fat bodies had disappeared after approximately 6 months of starvation. The indices of heart and kidney were not changed. 3. Glycogen concentration of the liver, ovaries and muscle were depleted nearly totally during the first half of the experimental time, whereas glycogen in the kidney seemed to be unaffected. 4. Protein concentration increased in the liver, decreased in the muscle and remained constant in the kidney. 5. Starvation caused an increase of the water concentration of the whole animal and different organs, especially at the end of the experiment. 6. The Na+/K+ ratio of the muscle increased significantly after 6 months of starvation and reached a maximum after 10 months. PMID- 2901322 TI - Reproduction of rock pigeon exposed to extreme ambient temperatures. AB - 1. The breeding biology of rock pigeon (Columba livia) exposed to ambient temperatures (Ta) between 50 and 60 degrees C was investigated. 2. Four families accomplished three complete life cycles after long term daily exposure to extreme Ta, with about 100% success. 3. The steady state temperatures in the nest were 60, 58, 53 and 44.6 degrees C in the air, substrate surface, underwing, and in the egg's microenvironment, respectively. 4. At thermal conditions between 30 and 60 degrees C, egg temperature (Tegg) was regulated between 36.8 +/- 0.8 (S.D.) and 41.7 +/- 0.4 (S.D.). Tegg increases by 0.163 degrees C/1 degree C rise in Ta. 5. Mean Tb of the nonincubating parent exposed to 30-60 degrees C is 41.6 +/- 0.6 degrees C (S.D.). Under the same conditions the incubating parent regulated a significantly (P less than 0.01) lower Tb (38.8 degrees C) at 45 degrees C Ta and about 1 degree C lower Tb at 30 and 60 degrees C Ta, respectively. 6. By comparing the differences between fast (5 min) cooling of hot egg (44.8 degrees C) to slow heating (60-90 min), we could demonstrate the high sensitivity of the incubating parent to the danger of embryo overheating. 7. The significance of the adaptive behavioral and physiological mechanisms in breeding under extreme thermal conditions are discussed. PMID- 2901324 TI - A molecular characterization of BALB/c congenic C.D2-Idh-1b, Lshr, Rep-1b, Pep-3b mice. PMID- 2901323 TI - Circannual fluctuations of the serum cortisol in the European ground squirrel, Citellus citellus L. AB - 1. Serum cortisol levels were measured throughout an annual cycle in male European ground squirrels, Citellus citellus L. 2. A circannual rhythm of these levels in euthermic animals was found: the highest being in late October, November and December, the lowest in May, early October and March. 3. The levels varied in the hibernating period as well: strongly reduced during the first part (October-December) and significantly elevated in the second one (January-March). 4. A significant elevation of the cortisol levels was marked 18-20 hr after full arousal from hibernation in October. PMID- 2901326 TI - Murine Hox genes--a multigene family. PMID- 2901325 TI - Identification of a linkage group including the Bcg gene by restriction fragment length polymorphism analysis. PMID- 2901327 TI - Expression of the homeobox genes Hox 2.1 and 2.6 during mouse development. PMID- 2901328 TI - Molecular studies of the parental origin and nature of human X isochromosomes. AB - X-chromosome restriction fragment length polymorphisms were used to determine the parental origin of the isochromosome in nine individuals with an i(Xq) or idic(Xq). We were able to specify the parental source of eight of the nine isochromosomes, with six being maternal and two paternal in origin. In two cases, one i(Xq) and one idic(Xq), we used Xq markers to determine the level of heterozygosity in the isochromosome. Each was homozygous at all tested loci, suggesting that each originated from a single X chromosome and not from an exchange of material between two X's. PMID- 2901330 TI - [Genes of Bos taurus caseins. Cloning and restriction analysis]. PMID- 2901329 TI - The effects of the somatostatin analogue SMS 201-995 on carbohydrate homeostasis of insulin-dependent diabetics as assessed by the artificial endocrine pancreas. AB - On the basis of the inhibitory actions of the somatostatin analogue SMS 201-995 on growth hormone (GH) and glucagon (IRG) secretion we investigated its effects on carbohydrate metabolism of insulin-dependent diabetics. Six patients with no residual insulin secretion were connected to the artificial endocrine pancreas (AEP) and after the establishment of a steady state overnight they were injected either normal saline or 50 micrograms of SMS 201-995 s.c., t.i.d., or 100 micrograms of the same compound b.i.d. Insulin requirements were assessed by the AEP and compared during the 24 h and after the main meals. The inhibition of GH and IRG secretion was evaluated as well. 50 micrograms of SMS analogue t.i.d. induced a significant reduction of insulin requirement (mean +/- SEM) while no significant difference was observed between control and 100 micrograms s.c., b.i.d., nor between 50 micrograms and 100 micrograms. The curve of glucose fluctuations was smoother after 50 micrograms than after 100 micrograms and control. Postprandial IRG secretion was inhibited by both regimens of SMS after lunch and dinner. GH secretion was significantly inhibited after all meals during the days of analogue administration. SMS 201-995 analogue appears to have a remarkable antidiabetic activity as shown by the sparing of administered amount of insulin, suppression of counter-insulin hormones and smoothing of blood glucose curve. It may constitute a safe and effective adjunctive measure in the management of insulin-dependent diabetics. PMID- 2901331 TI - [The growth of hematopoietic stem cells is inhibited by natural killers only in a non-syngeneic microenvironment]. PMID- 2901332 TI - Antihistaminic properties of cicletanine in human isolated coronary arteries. AB - Cicletanine was tested as an antagonist of the various actions of histamine in coronary artery rings isolated from old (mostly atherosclerotic) and young (non atherosclerotic) patients. Histamine mainly induced concentration-dependent contractions in arteries from old patients. Cicletanine antagonized this effect with a pA2 value of 6.9 (slope factor of 0.94), revealing in some cases a relaxant effect of histamine. In addition, cicletanine increased the threshold concentration of histamine required to trigger spastic, indomethacin-sensitive rhythmic contractions in (some) rings of the oldest patient. At variance with what occurred in coronary rings from old patients, the predominant effect of histamine in rings from young patients was relaxation. This relaxation remained unaltered by cicletanine (1 microM). As a whole, these results extend the histamine H1 antagonistic activity of cicletanine to human coronary arteries. If histamine is involved in the promotion of vasospasm, then cicletanine could be of potential benefit to patients, without apparently affecting the relaxant response to histamine in non-cardiac patients. PMID- 2901334 TI - [The 1987-88 epidemiological trend in HIV-1 and HIV-2 infections in Stuttgart and surroundings]. PMID- 2901333 TI - The effects of cicletanine, a new antihypertensive compound, on the flare and weal response to histamine. AB - This was an open experimental pilot study in five volunteers to identify any useful effect of cicletanine in the prevention or relief of the flare and weal response to histamine injection on the forearm. Areas of the flare and weal responses to three different concentrations of intradermal histamine injection were determined. Choice reaction time was measured to assess CNS performance. Heart rate, blood pressure and visual near-point were measured as indices of autonomic response. Oral cicletanine (200 mg) reduced the flare and weal response below pretreatment values for at least 8 h (p less than 0.05). There were no apparent changes in heart rate or visual near-point, nor any sedative effects. Diastolic blood pressure was significantly elevated 6 and 8 h after cicletanine (p less than 0.05) but systolic blood pressure was not affected. These results show that cicletanine is a potent non-sedative antihistamine compound. PMID- 2901335 TI - Coding sequence and expression of the homeobox gene Hox 1.3. AB - We have characterized Hox 1.3 (previously described as m2), a murine homeobox containing gene, which is a member of the Hox 1 cluster located on chromosome 6. A cloned cDNA was isolated from an Okayama-Berg library generated from the chemically transformed cell line MB66 MCA ACL6. The protein sequence of 270 amino acids was deduced from the nucleotide sequence of an open reading frame containing the homeobox. The open reading frame is interrupted at the genomic level by a 960 bp intron and is organized in two exons. The Hox 1.3 protein was found to contain extensive sequence homology with the murine homeodomain protein Hox 2.1, which is encoded on chromosome 11. There are two homology with the regions in the first exon, i.e. a hexapeptide conserved in many homeobox containing genes and the N-terminal domain, which was found to be homologous only to Hox 2.1. Furthermore, in exon 2 the homologies of the homeodomain regions are extended up to the carboxy terminus of Hox 1.3 and Hox 2.1. During prenatal murine development, maximal expression of Hox 1.3 is observed in 12-day embryonic tissue. The two transcripts carrying the Hox 1.3 homeobox are 1.9 kb and about 4 kb in length. An abundant Hox 1.3-specific 1.9 kb RNA is also found in F9 cells which were induced for parietal endoderm differentiation, whereas F9 teratocarcinoma stem cells do not stably express this specific RNA. Induction of the transcript occurs immediately after retinoic acid/cAMP treatment and the RNA level remains high for 5 days. Thus, the kinetics are different from the previously described homeobox transcripts Hox 1.1 and Hox 3.1. Interestingly, by analogy to the F9 cell system a negative correlation between transformation and Hox 1.3 expression is observed in 3T3 fibroblasts also. Untransformed 3T3 cells carry abundant 1.9 kb Hox 1.3 RNA, whereas the methylcholanthrene-transformed MB66 and LTK- cells or 3T3 cells transformed by the oncogenes src, fos or SV40 T antigen express only low levels. PMID- 2901337 TI - [At what point is premature labor to be arrested?]. PMID- 2901336 TI - Regulation of neurotransmitter metabolic enzymes and tyrosine hydroxylase mRNA level by nerve growth factor in cultured sympathetic neurones. AB - The survival of new-born rat sympathetic neurones in culture was increased in a dose-dependent manner by 7S nerve growth factor (NGF). NGF also increased, in a parallel manner, the specific activities of tyrosine hydroxylase (TOH) and choline acetyltransferase (CAT). Total acetylcholinesterase (AcChE) activity increased with NGF concentration, although less distinctly than TOH and CAT. However, NGF caused a large induction of the asymmetric A12 form of AcChE, and to a lesser extent of the globular G1 and G2 forms, whereas the globular G4 form was little affected. This suggests that NGF differentially regulates the synthesis and/or assembly of the various AcChE molecular forms. The levels of TOH mRNA in neurone cultures grown with increasing NGF concentrations were measured by Northern blot analysis with a rat cDNA probe. To correct for variations in the total mass of RNA per neurone, the filters were rehybridized with an 18S rRNA probe. The level of TOH mRNA, measured by the ratio (TOH:18S) of the hybridization signals increased 3.4-fold between 92 and 740 ng ml-1 7S NGF. Increases of TOH specific activity of the same order of magnitude were observed in sister cultures. The deficit in the level of mature TOH mRNA at low NGF concentration was not accompanied by a compensatory accumulation in unprocessed TOH transcripts. As TOH induction is insensitive to RNA polymerase inhibitors, we suggest that NGF regulates the maturation of TOH pre-mRNAs, and that the unprocessed transcripts are rapidly degraded. The long-term regulation of TOH by NGF may thus constitute a case of process-versus-discard control, as defined by J.E. Darnell. PMID- 2901338 TI - Delayed release formulation of the somatostatin analog RC-160 inhibits the growth hormone (GH) response to GH-releasing factor-(1-29)NH2 and decreases elevated prolactin levels in rats. AB - Recently, we have developed a long-acting delivery system for our somatostatin (SS) analog RC-160 based on injectable microcapsules in poly-(D,L-lactide coglycolide). We studied the capacity of this formulation to repeatedly block the GH secretion induced by administration of GRF-(1-29)NH2 (GRF) on different days. Male rats anesthetized with pentobarbital were injected iv with 2.5 micrograms/kg BW GRF-(1-29)NH2 or saline. Five minutes later, blood samples were taken for GH measurement, and the animals were injected im with RC-160 microcapsules at a dose calculated to release 25 micrograms/day of the analog for 7 days or with the vehicle. The GRF stimuli were repeated 48 h, 96 h, and 8 days after administration of SS analog in microcapsules. GRF administration increased GH levels at the four times tested (P less than 0.01) in the control group injected with vehicle, while RC-160 microcapsules inhibited the GH response for more than 96 h (P less than 0.01). The GH levels augmented by pentobarbital were also decreased by the RC-160 microcapsules (P less than 0.01). Animals treated with microcapsules showed smaller increases in their body weight than untreated rats (P less than 0.05). We also investigated the effect of RC-160 microcapsules on hyperprolactinemic female rats implanted with pituitary glands under the kidney capsules. High PRL levels in rats bearing pituitary grafts showed a significant decrease when measured 4 days after the administration of RC-160 microcapsules. These results demonstrate the efficacy of the long-acting delivery system of the SS analog RC-160 and suggest the possible clinical usefulness of this formulation for lowering GH and PRL levels. PMID- 2901339 TI - Norepinephrine is a possible neurotransmitter stimulating pulsatile release of luteinizing hormone-releasing hormone in the rhesus monkey. AB - The hypothesis that norepinephrine (NE) plays a facilitatory role in controlling the pulsatile release of LHRH was tested with a modified push-pull perfusion technique in conscious rhesus monkeys. The in vivo LHRH release in perfusate samples collected from the stalk-median eminence of ovariectomized females was pulsatile and synchronous with pulsatile LH release. Catecholamines measured in aliquots of perfusate samples revealed that in vivo NE release was also pulsatile and was synchronous with LHRH release. Local infusion of NE or methoxamine (an alpha 1-adrenergic stimulant) through a push cannula stimulated LHRH release, while iv injection of prazosin (an alpha 1-adrenergic blocker) suppressed LHRH release. It is concluded that NE is a possible neurotransmitter stimulating pulsatile LHRH release. PMID- 2901340 TI - Physiological role of growth hormone (GH)-releasing factor and somatostatin in the dynamics of GH secretion in adult male rat. AB - To investigate the physiological role of GRF and somatostatin (SRIF) in GH secretion in adult male rats, we prepared in vitro models using the perifusion system of cultured rat anterior pituitary cells exposed to various combinations of human GRF-(1-44)NH2 (hGRF) and SRIF. We studied the following three models on GRF secretion: 1) pulsatile GRF secreted at 1-h intervals, 2) pulsatile GRF secreted at 3-h intervals, and 3) GRF continuously secreted. When 5-min pulses of 20 nM GRF were delivered at 1-h intervals, the responses to GRF gradually declined. The addition of continuous 20 nM SRIF with short pauses prevented this attenuated response and produced high peaks of GH at 3-h intervals. When 5-min pulses of 20 nM GRF were delivered at 3-h intervals, three high peaks of GH were observed regardless of the addition of SRIF. Pretreatment with GRF pulses enhanced the peaks of GH during SRIF pauses. When 20 nM GRF was continuously delivered, a rapid attenuated response to GRF was observed. Although the addition of continuous 20 nM SRIF with short pauses produced three small peaks of GH, these results were caused by the post-SRIF rebound release. These observations suggest that preexposure to prolonged SRIF can prevent an attenuated response to repeated GRF pulses, and that pretreatment with GRF pulses enhances post-SRIF rebound release. PMID- 2901341 TI - Effect of truncated glucagon-like peptide-1 [proglucagon-(78-107) amide] on endocrine secretion from pig pancreas, antrum, and nonantral stomach. AB - We studied the effect of truncated glucagon-like peptide-1 [naturally occurring GLP-1; proglucagon-(78-107) amide], a potent insulinotropic peptide from the pig ileum, on endocrine and exocrine secretion of potential gastrointestinal target organs using isolated perfused preparations of the porcine pancreas, antrum, and nonantral part of the stomach. Truncated GLP-1 significantly increased somatostatin secretion from the pancreas at 10(-10) mol/liter and more than doubled the secretion at 10(-9) mol/liter, but had no effect on either somatostatin or gastrin secretion from the antrum or on somatostatin secretion from the nonantral stomach in concentrations up to 10(-8) mol/liter. Insulin secretion from the pancreas (with 7 mmol/liter glucose in the perfusate) increased 2-fold with truncated GLP-1 at 10(-10) mol/liter and almost 5-fold at 10(-9) mol/liter. Pancreatic glucagon secretion was inhibited by 50% at 10(-10) mol/liter and by 70-80% at 10(-9) mol/liter. Full-length GLP-1 [proglucagon-(72 107)] and GLP-2 [proglucagon-(126-159)] had no effect on hormone secretion from any of the perfused organs. It is concluded that truncated GLP-1 may participate in an entero-insular control of pancreatic endocrine secretion. PMID- 2901342 TI - Identification of a cellular receptor for transforming growth factor-beta in rat ventral prostate and its negative regulation by androgens. AB - Scatchard analyses of the binding of transforming growth factor-beta (TGF beta) to membranes from rat ventral prostate revealed the presence of high affinity (Kd = 140 pM) saturable binding sites for [125I]TGF beta. The binding of [125I]TGF beta to prostatic membranes, while displaced in the presence of excess unlabeled TGF beta, is unaffected by epidermal growth factor, nerve growth factor, fibroblast growth factor, or insulin, indicating the specificity of binding. Affinity labeling of these membrane receptors by covalent attachment to [125I]TGF beta with bis-(sulfosuccinimidyl)suberate and subsequent electrophoretic analysis of the labeled complexes revealed the specific binding of [125I]TGF beta to a macromolecule that predominantly migrates as a 260,000 mol wt band in 7.5% acrylamide gels. Castration-induced androgen deprivation produced a significant increase in [125I]TGF beta binding to prostatic membranes with no apparent change in the affinity of membrane receptors for TGF beta. TGF beta receptor levels per total gland increased approximately 2-fold by 3 days after castration, reached a peak value by day 4, and then declined during the subsequent 10 days. Androgen administration to 4-day castrated animals decreased the number of TGF beta receptors to a value similar to that in the intact controls. These results demonstrate the presence of specific binding sites for TGF beta in the rat ventral prostate. Furthermore, the TGF beta receptor levels seem to be under negative androgenic regulation, indicating a potential role for this growth factor in the mechanism of activation of castration-induced death of androgen dependent epithelial cells in the ventral prostate. PMID- 2901343 TI - Both positive and negative regulatory elements mediate expression of a photoregulated CAB gene from Nicotiana plumbaginifolia. AB - We have analyzed promoter regulatory elements from a photoregulated CAB gene (Cab E) isolated from Nicotiana plumbaginifolia. These studies have been performed by introducing chimeric gene constructs into tobacco cells via Agrobacterium tumefaciens-mediated transformation. Expression studies on the regenerated transgenic plants have allowed us to characterize three positive and one negative cis-acting elements that influence photoregulated expression of the Cab-E gene. Within the upstream sequences we have identified two positive regulatory elements (PRE1 and PRE2) which confer maximum levels of photoregulated expression. These sequences contain multiple repeated elements related to the sequence-ACCGGCCCACTT . We have also identified within the upstream region a negative regulatory element (NRE) extremely rich in AT sequences, which reduces the level of gene expression in the light. We have defined a light regulatory element (LRE) within the promoter region extending from -396 to -186 bp which confers photoregulated expression when fused to a constitutive nopaline synthase ('nos') promoter. Within this region there is a 132-bp element, extending from -368 to -234 bp, which on deletion from the Cab-E promoter reduces gene expression from high levels to undetectable levels. Finally, we have demonstrated for a full length Cab-E promoter conferring high levels of photoregulated expression, that sequences proximal to the Cab-E TATA box are not replaceable by corresponding sequences from a 'nos' promoter. This contrasts with the apparent equivalence of these Cab-E and 'nos' TATA box-proximal sequences in truncated promoters conferring low levels of photoregulated expression. PMID- 2901344 TI - Interdependence of CD3-Ti and CD2 activation pathways in human T lymphocytes. AB - Human T lymphocytes can be activated through either the antigen/MHC receptor complex T3-Ti (CD3-Ti) or the T11 (CD2) molecule to proliferate via an IL-2 dependent mechanism. To investigate the relationship of these pathways to one another, we generated and characterized Jurkat mutants which selectively express either surface CD3-Ti or CD2. Here we show that CD3-Ti- mutants fail to be stimulated by either pathway to increase phosphoinositide turnover, mobilize calcium or induce the IL-2 gene. The activation capacity of these mutants via CD2 as well as CD3-Ti can be restored following reconstitution of surface CD3-Ti expression upon appropriate DNA transfer (e.g. Ti beta subunit cDNA into Ti beta- Jurkat variants). Collectively, these results demonstrate that CD3-Ti and CD2 pathways are interdependent and that phosphoinositide turnover is linked to the CD3-Ti complex. PMID- 2901345 TI - Oncogenic activation of the neu-encoded receptor protein by point mutation and deletion. AB - The rat neu gene, which encodes a receptor-like protein homologous to the epidermal growth factor receptor, is frequently activated by a point mutation altering a valine residue to a glutamic acid residue in its predicted transmembrane domain. Additional point mutations have been constructed in a normal neu cDNA at and around amino acid position 664, the site of the naturally arising mutation. A mutation which causes a substitution of a glutamine residue for the normal valine at residue 664 leads to full oncogenic activation of the neu gene, but five other substitutions do not. Substituted glutamic acid residues at amino acid positions 663 or 665 do not activate the neu gene. Thus only a few specific residues at amino acid residue 664 can activate the oncogenic potential of the neu gene. Deletion of sequences of the transforming neu gene demonstrates that no more than 420 amino acids of the 1260 encoded by the gene are required for full transforming function. Mutagenesis of the transforming clone demonstrates a correlation between transforming activity and tyrosine kinase activity. These data indicate that the activating point mutation induces transformation through (or together with) the activities of the tyrosine kinase. PMID- 2901346 TI - Expression of multiple homeobox genes within diverse mammalian haemopoietic lineages. AB - Several mouse and human genes encoding the DNA-binding homeobox domain are implicated here in haematopoiesis, a differentiation process maintained throughout life. Four homeobox cDNA clones were isolated from bone marrow and spleen of adult mice and two from the human leukaemia cell line K562. They derive from the Hox 1.1, Hox 2.3, Hox 6.1 genes and two previously undescribed genes, one of a type (paired) not found before in vertebrates. A survey of 36 cell lines of the lymphoid, myeloid and erythroid lineages revealed that certain homeobox transcripts were almost ubiquitous, while others were restricted to certain lineages or even particular cell lines. The expression pattern altered in a myeloid and an erythroid line induced to terminal differentiation, and in novel lines that had switched from a lymphoid to a myeloid phenotype. Altogether, the haemopoietic compartment may contain up to 20 homeobox transcripts. In one myeloid leukaemia, DNA rearrangement has perturbed expression. These findings suggest that homeobox genes may influence developmental decisions within the haemopoietic system. PMID- 2901347 TI - Differential utilization of the same reading frame in a Xenopus homeobox gene encodes two related proteins sharing the same DNA-binding specificity. AB - Xenopus XlHbox 1 produces two transcripts during early development. One encodes a long open reading frame (ORF) and the other a short ORF sharing the same homeodomain, but differing by an 82 amino acid domain at the amino terminus. The long protein amino terminus is conserved with many other homeodomain proteins, and its absence from the short protein could have functional consequences. Some viral genes also utilize a single ORF to encode transcription factors of antagonistic functions. The overall organization of the homologous genes in frog and man is similar, supporting the notion that both transcripts are of functional significance. Studies on XlHbox 1 function show that the region common to the long and short proteins has a sequence-specific DNA-binding activity, and that microinjection of specific antibodies into embryos results in the loss of structures derived from cells normally expressing XlHbox 1. PMID- 2901350 TI - Effects of beta-adrenergic blockade on training-induced structural adaptations in rat left ventricle. AB - The study was designed to evaluate the effects of eight weeks of exercise training or training-beta-adrenergic blockade combination on gross and microscopic alterations of rat cardiac muscle and microvascular bed. Rats were randomly assigned to either sedentary control (C), trained (T), metoprolol trained (MT), or propranolol-trained (PT) groups. The training protocol involved treadmill running for 8 weeks at 0.5 ms-1, 20% grade. Earlier experiments by us showed this training protocol to be effective in producing significant changes in selected skeletal muscle enzyme activities in all trained groups. In the current study an absolute reduction in left ventricular (LV) weight was observed in the PT compared to the C group (0.91 +/- 0.02 vs. 1.04 +/- 0.04 g, P less than 0.05). LV weight in the T and MT groups was no different from C so that LV to BW ratio (mg.g-1) was significantly increased (P less than 0.05) due to a similar reduction in body weight (BW) in all three training groups. Morphometric analysis of LV myocardium revealed no significant differences in myocyte mean cross sectional area (micron 2) in any of the groups (289 +/- 16-C, 332 +/- 20-T, 281 +/- 44-MT, and 273 +/- 12-PT). Capillary density independently calculated by light and electron microscopy was unchanged by training or training-beta-blockade combination. It was concluded that training of sufficient intensity and duration to produce skeletal muscle enzyme adaptations does not necessarily produce myocyte hypertrophy or alter LV capillarity. Additionally functioning beta adrenergic receptors appear to play a role in both the central and peripheral adaptations to endurance exercise training. PMID- 2901351 TI - Permeation of hydrophilic molecules through the outer membrane of gram-negative bacteria. Review on bacterial porins. PMID- 2901348 TI - A novel, tissue-specific, Drosophila homeobox gene. AB - The homeobox gene family of Drosophila appears to control a variety of position specific patterning decisions during embryonic and imaginal development. Most of these patterning decisions determine groups of cells on the anterior-posterior axis of the Drosophila germ band. We have isolated a novel homeobox gene from Drosophila, designated H2.0. H2.0 has the most diverged homeobox so far characterized in metazoa, and, in contrast to all previously isolated homeobox genes, H2.0 exhibits a tissue-specific pattern of expression. The cells that accumulate transcripts for this novel gene correspond to the visceral musculature and its anlagen. PMID- 2901349 TI - Protein/DNA architecture of the DNase I hypersensitive region of the Drosophila hsp26 promoter. AB - Genomic footprinting on the Drosophila hsp26 promoter in isolated nuclei has shown that a TATA box binding factor is present before and after induction by heat shock, while three of the seven heat shock consensus sequences 5' of the gene are occupied (presumably by heat shock factor, HSF) specifically on heat shock. The sites of HSF interaction are separated by greater than 200 bp of which approximately 150 bp are bound to the surface of a nucleosome. The juxtaposition of these various macromolecules on the DNA suggests a basis for the major DNase I hypersensitive site 5' of hsp26 and a novel tertiary structure for the promoter complex. PMID- 2901352 TI - Protease-nicked theta-toxin of Clostridium perfringens, a new membrane probe with no cytolytic effect, reveals two classes of cholesterol as toxin-binding sites on sheep erythrocytes. AB - A nicked theta-toxin (C theta), obtained by limited proteolysis with subtilisin Carlsberg, causes almost no hemolysis while it retains a nearly intact cholesterol binding site below 20 degrees C. Neither electron microscopic evidence for the formation of arc- and ring-shaped structures on the membrane nor toxin-stimulated influx of extracellular Ca2+ are detected in C theta-treated cells below 20 degrees C. Thus, event(s) in the lytic process are responsible for the temperature dependency of hemolysis, which is also supported by the observation that C theta requires higher Arrhenius activation energy for hemolysis than the native toxin. Using C theta as a probe due to its high affinity for membrane cholesterol without causing any obvious membrane changes, we demonstrated the possible existence of high- and low-affinity sites for theta toxin on sheep erythrocytes. Both binding sites disappear by simultaneous treatment of the cells with sublytic doses of digitonin. Furthermore, C theta binds only to cholesterol among the chloroform/methanol-extractable, lipid components of sheep and human erythrocytes but not to the protein components derived from them. These results strongly suggest that cholesterol is an essential component of the both high- and low-affinity sites, and also imply that the modes of existence of cholesterol in the red cell membrane are heterogeneous. PMID- 2901354 TI - Radiation sensitivity and study of glutathione and related enzymes in human colorectal cancer cell lines. AB - A panel of 13 human colorectal cell lines was studied, with these lines exhibiting a histological profile similar to that observed in clinical practice. In the five lines tested, variable sensitivity to radiation was observed, from the relatively sensitive NCI-H716 to the highly resistant line NCI-H630, with the latter cell line derived from a patient who had previously received radiation treatment. Glutathione levels and glutathione related enzyme activity varied widely between all 13 cell lines, showing no relationship to radiation sensitivity. The variability observed suggests that some colonic tumours may be responsive to radiation, although their identification remains difficult. However, this may prove possible by incorporation of recently developed cell adhesive matrix assays using survival following a 2 Gy radiation dose as a parameter of radiation sensitivity. This panel of human cancer cell lines offers an ideal model for the study of parameters affecting the radiosensitivity and chemosensitivity pattern of colorectal cancer cells. PMID- 2901353 TI - Diethylstilbestrol. Interactions with membranes and proteins and the different effects upon Ca2+- and Mg2+-dependent activities of the F1-ATPase from Rhodospirillum rubrum. AB - The hydrophobic compound diethylstilbestrol inhibits the generation of the proton gradient and the membrane potential in chromatophores from Rhodospirillum rubum and dissipates proton gradients over asolectin vesicle membranes. The Ca2+-ATPase activity of chromatophores, of purified F0F1-ATPase and of purified F1-ATPase is also decreased in the presence of diethylstilbestrol. Other repressed activities are the pyrophosphatase activity of soluble pyrophosphatase from yeast and the NADH oxidation by L-lactate:NAD oxidoreductase. We have previously reported that also ATP synthesis, PPi synthesis and PPi hydrolysis of R. rubrum chromatophores are inhibited by diethylstilbestrol [Strid et al. (1987) Biochim. Biophys. Acta 892, 236-244]. Addition of bovine serum albumin reverses or prevents diethylstilbestrol-induced inhibition of the activities tested. On the other hand, the Mg2+-ATPase activity of chromatophores, purified F0F1-ATPase and purified F1-ATPase are stimulated by low concentrations of diethylstilbestrol. On the basis of its hydrophobicity and the reversal of its inhibition by bovine serum albumin, diethylstilbestrol is proposed to act unspecifically on membranes and at hydrophobic domains of proteins. Such an attack upon the subunits of the F1-ATPase, altering the subunit interactions, is proposed to explain the different results obtained for the Ca2+-ATPase and the Mg2+-ATPase. PMID- 2901356 TI - Species conservation of the T cell lymphocyte CD2 cell surface antigen. AB - A rabbit polyclonal antiserum was raised against a synthetic peptide, termed CD2 300, comprizing 18 amino acid resides which are conserved among the cytoplasmic domains of the human, rat and mouse CD2 antigens. Cross-depletion experiments showed that the CD2 monoclonal antibody OKT11 and purified CD2-300 antibodies (Ab) precipitated the same molecules from the surface of human T lymphoblasts. The results of immunoprecipitation analyses indicated that the purified CD2-300 Ab were specific for human and mouse CD2, and that the CD2-300 peptide competitively and specifically inhibited precipitation by CD2-300 Ab in both species. When employed to stain murine tissues, the CD2-300 Ab gave the anticipated pattern of distribution for the CD2 antigen, although there was some nonspecific labeling of non-T cells. PMID- 2901355 TI - The required interaction between monocytes and peripheral blood T lymphocytes (T PBL) upon activation via CD2 or CD3. Role of HLA class I molecules from accessory cells and the differential response of T-PBL subsets. AB - Previously, we have shown that paraformaldehyde-fixed monocytes are able to fully complement, in terms of [3H]dThd incorporation, a primary stimulus delivered to purified T cells by monoclonal antibodies (mAb) reacting with CD3 or CD2 molecules. Here, we show that depending on the stimulus used (CD3 mAb or different pairs of CD2 mAb) HLA class I molecules from monocytes are directly involved in complementary signals provided to T cells. This was evidenced by the following observations: (a) mAb reacting with the heavy or light chain of class I molecules, or their Fab fragments, completely blocked proliferation of peripheral blood lymphocytes (PBL) activated by CD3 mAb; (b) mAb against the heavy chain of HLA class I but not against beta 2-microglobulin partially blocked (approximately equal to 50%) PBL activation by the CD2 "GT2 + T111" mAb pair but did not block activation by CD2 "D66 + T111" mAb; (c) this pattern of inhibition was observed when anti-class I mAb were used in the soluble phase or when they were bound to monocytes subsequently fixed with paraformaldehyde and cultivated with purified autologous T cells; (d) fixed monocytes are able to restore interleukin (IL) 2 receptor expression on purified T cells stimulated by CD3 mAb or CD2 "GT2 + T111", contrary to anti-HLA class I mAb-pretreated monocytes. The inhibitory effects of anti-HLA class I mAb bound to monocytes were not found to be reversed by recombinant IL2 or recombinant IL1. We assume that HLA class I would be involved in two or more signals delivered to T cells by monocytes, the requirement in those signals depending on the initial stimulus applied to T cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901357 TI - Clorgyline treatment differentially affects m-chlorophenylpiperazine-induced neuroendocrine changes. AB - Intravenous administration of the 5-HT1B agonist, m-chlorophenylpiperazine (m CPP) to rats produced increases in plasma prolactin (peak effect at 15 min), corticosterone (peak effect at 30 min) and a decrease in plasma growth hormone (peak effect at 15 min) concentrations. Short-term or long-term clorgyline treatment did not affect baseline levels of prolactin, corticosterone or growth hormone. Short-term clorgyline treatment attenuated m-CPP's effect on corticosterone but not on prolactin or growth hormone. On the other hand, long term clorgyline treatment attenuated m-CPP's effect on prolactin but not on corticosterone or growth hormone. These findings are compatible with development of functional subsensitivity of 5-HT1B receptors mediating prolactin release following long-term clorgyline treatment. Attenuation of m-CPP's effect on corticosterone following short-term clorgyline treatment suggests either early adaptational changes in a 5-HT receptor subtype mediating corticosterone release, or clorgyline-induced increases in other neurotransmitters such as norepinephrine which may be responsible for attenuating m-CPP's effect on corticosterone. PMID- 2901358 TI - Central effects of the potent and highly selective mu opioid antagonist D-Phe-Cys Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) in mice. AB - The ability of the selective cyclic mu-opioid receptor antagonist, D-Phe-Cys-Tyr D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), to inhibit the acute and chronic effects of morphine in vivo was studied in mice. Intracerebroventricular (i.c.v.) administration of CTOP antagonized the analgesic effect of morphine in a dose dependent manner, as measured by the heat-irradiant (tail-flick) method. CTOP was more effective than naloxone in inhibiting analgesia on a molar basis. CTOP also antagonized the acute morphine-induced hypermotility. CTOP caused withdrawal hypothermia and a loss of body weight in morphine-dependent animals. After the development of morphine-induced chronic dependence, CTOP administered i.c.v. caused a dose-dependent loss of body weight and hypothermia, and was about 10-400 times more potent than naloxone. CTOP administered alone to drugnaive mice did not cause antinociception, changes in body weight or body temperature. PMID- 2901359 TI - Corticotropin-releasing factor activates tyrosine hydroxylase in rat and mouse striatal homogenates. AB - Corticotropin-releasing factor (CRF) caused a concentration-dependent increase in dopamine (DA) synthesis measured in rat striatal synaptosomes. The concentrations of CRF producing half-maximal and maximal stimulation were 40 and 300 nM, respectively. The maximal effect corresponded to a 34% increase from the control level of DA synthesis. CRF 1 microM increased DA synthesis in synaptosomes of mouse striatum by 48%. Pretreatment of striatal synaptosomes with CRF produced a persistent activation of tyrosine hydroxylase assayed in extracts of lysed synaptosomes. These results suggest that CRF may play a modulatory role in striatal DA synthesis by acting on receptors located on DA terminals. PMID- 2901360 TI - Long-term benzodiazepine treatment reduces neuronal responsiveness to cholecystokinin: an electrophysiological study in the rat. AB - Acute benzodiazepine administration has been reported to antagonize the effect of cholecystokinin both in the periphery and in the central nervous system. A two week treatment with either diazepam (5 mg/kg per day) or flurazepam (15 mg/kg per day) markedly reduced the excitatory effect of microiontophoretically applied sulphated cholecystokinin octapeptide-(26-33) on rat CA3 hippocampal pyramidal neurons but not that of acetylcholine. In view of the sustained anxiolytic activity of benzodiazepines that contrasts with their transient sedative effect, the present results suggest that the reduction of neuronal responsiveness to cholecystokinin by these drugs might be related to their anxiolytic property. PMID- 2901361 TI - Glycine reverses antagonism of N-methyl-D-aspartate (NMDA) by 1-hydroxy-3 aminopyrrolidone-2 (HA-966) but not by D-2-amino-5-phosphonovalerate (D-AP5) on rat cortical slices. PMID- 2901362 TI - A proconvulsant action of selective alpha 2-adrenoceptor antagonists. AB - The effects of alpha 2-adrenoceptor agonists and antagonists were examined on seizure thresholds determined by intravenous infusions of convulsants in rodents. alpha 2-Adrenoceptor antagonists were proconvulsant; dose dependently reducing the threshold for pentylenetetrazol- or bicuculline-induced tonic seizures. Strychnine-induced tonic seizures were unaffected. The alpha 2-adrenoceptor agonists clonidine, BHT-933 and UK 14,304 did not modify pentylenetetazol-induced seizures at low or moderate doses but at high doses clonidine and BHT-933 were proconvulsant. The facilitatory effect of alpha 2-adrenoceptor antagonists on pentylenetetrazol-induced tonic seizures was blocked by clonidine or UK 14,304. The proconvulsant action of alpha 2-adrenoceptor antagonists was contrasted with that of ethyl-beta-carboline-3-carboxylate, a benzodiazepine receptor contragonist, which markedly reduced the threshold for seizure initiation rather than the tonic seizure threshold. The selective facilitatory action of alpha 2 adrenoceptor blockade on tonic seizures suggests that a noradrenergic mechanism is involved in the control of seizure propagation rather than seizure initiation. PMID- 2901363 TI - Behavioural and neurochemical effects of antipamezole, a novel alpha 2 adrenoceptor antagonist. AB - The effects of antipamezole (MPV-1248), a novel selective and specific alpha 2 adrenoceptor antagonist, were studied on monoamine metabolism in rat brain and CSF. In addition, the ability of the drug to antagonize the behavioural and neurochemical effects of two alpha 2-adrenoceptor agonists, detomidine and medetomidine, was assessed. Atipamezole, 0.03-3.0 mg/kg, had no gross behavioral effects on the rats. Above 3 mg/kg, the rats showed increased vocalization and some hostility, rapid breathing and piloerection. The drug caused dose-dependent, rapid and relatively long-lasting increase in the central turnover of noradrenaline (NA) as reflected by increases in the levels of the major metabolites of NA in brain and CSF and an increase in the depleting effect of alpha-methyl-para-tyrosine on brain NA levels. An increase in the turnover of serotonin (5-HT) in brain was indicated by a decrease in the concentration of 5 HT and a corresponding increase in the level of its metabolite, 5 hydroxyindoleacetic acid. Atipamezole was able to antagonize the sedative, hypothermic and neurochemical effects of two potent alpha 2-agonists, detomidine and medetomidine. These results give support for the characterization of atipamezole as a potent antagonist at central alpha 2-adrenoceptors with a rapid onset of action. PMID- 2901364 TI - [Elevated immunoreactive-somatostatin levels in the brain of ataxic mutant mice]. AB - Immunoreactive-somatostatin (IR-SRIF) levels were investigated in the brain of 4 types of ataxic mice (Rolling Mouse Nagoya, Weaver, PCD, Staggerer) with different cerebellar pathologies. IR-SRIF concentrations (ng/mg) were found to be significantly elevated in both cerebellum and cerebrum of all ataxic mutant mice, IR-SRIF (ng/organ) was found to be increased in the cerebellum and cerebrum in Rolling Mouse Nagoya and PCD compared with control mice. The gel-filtration profile (Sephadex G-50) in the cerebellar extracts of Rolling Mouse Nagoya proved to be identical to that of control mice. Three peaks of IR-SRIF were found to be uniformly elevated in Rolling Mouse Nagoya, with the highest peak coinciding with authentic somatostatin-14. The present results suggest that elevated levels of IR SRIF in the brain may play a role in the mechanism underlying the manifestation of ataxia in ataxic mutant mice, especially in Rolling Mouse Nagoya and PCD. PMID- 2901365 TI - [A modified Tanabe-Chiba medium for detection of Entamoeba histolytica]. AB - Tanabe-Chiba's (T-C) medium, which has been routinely used for detection of Entamoeba histolytica in feces in Japan, was modified by adding some commercially available enrichments to the liquid part and by eliminating the agar slant. This is tentatively called M medium. M medium and T-C medium were compared for their efficiency for detecting E. histolytica in the feces of monkeys. No significant difference in the detection rate was found between the two media. However the rate of multiplication of the amoebae in M medium was significantly higher than that in T-C medium within the limited time of 24-48 h of cultivation. PMID- 2901366 TI - A sigmoidal relationship between liver stearoyl CoA desaturase activity and serum hormone concentrations caused by streptozocin and its antagonists. AB - Stearoyl CoA desaturase activity in liver microsomes, and insulin, thyroxine, and triiodothyronine levels in serum were measured after administration of streptozocin (STZ) and its antagonists to rats. The effect of STZ, which caused hyperglycemia and inhibited the desaturase activity, was antagonized by 2 desoxyglucose and 3-O-methyl-glucose; 1-O-methyl-3-desoxyglucose and 1-O-methyl-3 O-methylglucose were without any effect. The enzyme activity plotted against insulin levels showed a broad sigmoidal curve, whereas the activities versus thyroid hormone levels showed steeper sigmoidal curves. PMID- 2901367 TI - [The anti-H1-histaminic and antimuscarinic effect of 2- and 4-[benzyl-(2 dimethylaminoethyl)amino]pyrimidine compounds]. AB - This paper reports the synthesis of 2- and 4- [benzyl-(2 dimethylaminoethyl)amino]pyrimidine compounds and the evaluation of their inhibitory properties against histamine (H1), acetylcholine and barium chloride, on guinea pig isolated ileum. 4-[p.Methoxybenzyl-(2-dimethylaminoethyl)amino]-2 methoxy-pyrimidine (VIII) is shown to possess H1 receptor antagonist activity, with a potency similar to that observed for Tonzylamine. By contrast, a specific, although weak, antimuscarinic effect is displayed by 4-[benzyl-(2 dimethylaminoethyl)amino]-2-methoxy-5-methylthio-pyrimidine (XII). PMID- 2901368 TI - Medications in angina. PMID- 2901370 TI - [Autoregulation of the cerebral blood flow in normo- and hypertensive rats under beta-adrenoreceptor blockade]. AB - A disorder in the autoregulation of cerebral blood flow due to a drop of arterial blood pressure (shift to the right) occurred earlier in hypotensive rats than in normotensive ones. A beta-adrenergic blockade (obsidan) improved the autoregulation (shift to the left) in both normo- and hypertensive animals. PMID- 2901369 TI - [Excitatory beta-adrenoreceptors on cholinergic interneurons of the myenteric plexus]. AB - Contractile responses of small intestine segments to isopropylnoradrenaline (INA) disappeared after the blockade of M- and N-cholinoreceptors, beta-adrenoreceptors and increased after the blockade of alpha-adrenoreceptors. Infusion of acetylcholine in subthreshold doses enhanced the small intestine contractile responses to the INA. The blockade of beta-adrenoreceptors with propranolol reduced contractile responses to exogenous (i. a. administration) and endogenous (electrical stimulation of the n. vagus' efferent fibers) acetylcholine, histamine and bradykinin. Stimulation of beta-adrenoreceptors with the INA enhanced contractile responses to exogenous acetylcholine and histamine and reduced the responses to bradykinin. The data obtained suggest the existence of activating beta-adrenoreceptors, apart from alpha- and beta-inhibitory adrenoreceptors, in the small intestine. Activating beta-adrenoreceptors are situated on cholinergic interneurons of the myenteric plexus and mediate the activating effect of endogenous catecholamines upon cholinergic neurons of small intestine. PMID- 2901372 TI - [Mechanisms of "warm" tachycardia and "cold" bradycardia in cats]. AB - The infusion of a small volume of blood with temperature higher ("warm") or below ("cold") the temperature of atrial blood into the right atrium induced "warm" tachycardia and "cold" bradycardia, resp., in anesthetized and in alert cats. Infusion of the blood with temperature equal to that of atrial blood induced no changes of the heart rate. Infusion of the same volume of "cold" or "warm" blood after adreno- and cholinoreceptor-blocking agents was accompanied by a less severe tachycardia or bradycardia. There seem to be two mechanisms in the initiation of the above effects: the neural and the myogenic ones. PMID- 2901371 TI - [Influence of a blockade of adrenergic and M-cholinergic structures on the hemodynamic effects of prostaglandin E2]. AB - In 22 dogs, blockade of adrenergic and M-cholinergic structures reduced hemodynamic effect of prostaglandin E2. After blockade of beta-adrenoreceptor the injection of prostaglandin E2 induced lesser changes in hemodynamic values than after blockade of alpha-adreno- and M-cholinoreactive structures. PMID- 2901373 TI - [Effect of dopamine on the blood flow in various zones of the kidney cortex and medullary layer in rats]. AB - Phentolamine and propranolol did not alter the kidney response to dopamine whereas haloperidol completely prevented the dopamine vascular and channel effects. The agents inhibiting cyclooxygenase and kallikrein-kinin system do not interfere with an increase in the blood flow or depressing action of the neurotransmitter upon sodium transport in the nephron. The hemodynamic shift occurring under the effect of dopamine in different areas of renal tissue seems to be due to a selective stimulation of vascular DA-receptors and unrelated to an increase in the production of prostaglandins and kinins in the kidneys. PMID- 2901374 TI - Species specificity in cell-substrate interactions in medusae. AB - A new system is described for the study of ECM-tissue interactions, using the ECM (called mesogloea) of various cnidarians and isolated striated muscle and endodermal tissue of jellyfish. The mesogloea consists mainly of water and collagen. It is present in all cnidarians and can be isolated without enzyme treatment. It can be used as a substrate to which cells and tissues adhere and on which they spread and migrate. Tissues of striated muscle and endoderm adhere and spread not only on mesogloea from regions they normally cover, but also from other regions of the animal. However, adhesion and spreading are highly species specific. Species-specific adhesion is found throughout the whole mass of mesogloea even at regions where cells do not occur naturally. The cell adhesion factor can be extracted from the mesogloea so that the mesogloea no longer shows any cell adhesion properties. The extract consists mainly of a cysteine containing collagen. PMID- 2901375 TI - Association of susceptibility to spontaneous diabetes in rat with genes of major histocompatibility complex. AB - This study was designed to map the diabetes susceptibility gene(s) associated with the rat major histocompatibility complex (MHC) RT1. We have crossed spontaneously diabetic male rats bearing the recombinant RT1r8 haplotype with female rats of the AC1.1r4 congenic strain. Three diabetic rats were determined to be homozygous for the r4 haplotype by serotyping. The absence of recombination within the MHC was confirmed by inspection of restriction-fragment-length patterns of the diabetic animals and the parental strains. In conjunction with previous breeding studies, this study maps the diabetes susceptibility gene to the right of the RT1-A locus and to the left of the RT1-C locus. A low incidence of diabetes in the F2 (4.5%) emphasizes the multifactorial nature of the susceptibility. The presence of depressed responsiveness of peripheral blood lymphocytes to concanavalin A stimulation increases the prevalence of the overt disease. An unusual feature of the diabetic syndrome in this study is the sparse or absent pancreatic lymphocytic inflammatory response, with true insulitis being a rare finding. PMID- 2901376 TI - Glucoregulatory function of glucagon in hypo-, eu- and hyperthyroid miniature pigs. AB - The glucoregulatory function of glucagon was investigated in hypo-, eu- and hyperthyroid miniature pigs. Infusion glucagon, (3 ng x kg body weight-1.min-1) transiently increased blood glucose (p less than 0.01) and hepatic glucose production (p less than 0.01) in euthyroidism, but was without effect in hyperthyroidism. Infusing glucagon plus somatostatin (2 ng x kg body weight-1.min 1 and 0.2 microgram x kg body weight-1.min-1) transiently increased blood glucose (delta 3.0 to 4.3 mmol/l) and hepatic glucose production (delta 3.3 to 7.7 mumol x kg body weight-1.min-1) in all thyroid states, the effect was less pronounced in hyperthyroid pigs. By contrast, hypoglucagonaemia (74 to 107 pg/ml) at basal insulin (28 to 35 microU/ml) provoked hypoglycaemia (1.4 to 2.2 mmol/l) and a fall in glucose production (delta 4.7 to 8.3 mumol x kg body weight-1.min-1), which was independent of the thyroid state; the effect was most pronounced in hyperthyroidism (p less than 0.01). Hepatic glycogen content, arterial gluconeogenic precursor concentrations as well as the glycaemic response (delta 0.60 mmol/l) to alanine infusion (23 mumol x kg body weight-1.min-1) were all unaffected by hyperthyroidism. We conclude that moderate experimental hyperthyroidism reduces glucagon action due to reduced glycogen mobilisation. This may in part result from increased insulin sensitivity. PMID- 2901377 TI - First phase of insulin secretion stimulated by glucose plus theophylline and inhibitory effect of somatostatin in genetically diabetic mice (C57BL/KsJ-mdb). AB - In a previous study in C57BL/KsJ mdb/mdb mice aged 4 to 12 days we observed a diminished first phase of glucose-induced insulin secretion in vitro, and alterations in the inhibitory effect of somatostatin on insulin secretion. This study explores, using perifused pancreatic slices, whether the reduced B-cell responsiveness to somatostatin in mdb/mdb mice can be overcome upon induction of a biphasic insulin release by using theophylline. Under these conditions our results show: (1) in mdb/mdb mice aged 4 to 6 days, the restoration of the first peak of insulin secretion overcomes the reduced B-cell sensitivity to somatostatin; and (2) in mdb/mdb mice aged 7 to 12 days, the addition of theophylline only causes a partial restoration of B-cell responsiveness to somatostatin, suggesting that other mechanisms could be involved in the progressive impairement of B-cell sensitivity to somatostatin inhibitory effect. PMID- 2901378 TI - Metformin enhances certain insulin actions in cultured rat hepatoma cells. AB - The effect of the oral antidiabetic agent metformin on insulin regulation of glycogen metabolism, tyrosine-aminotransferase activity, and [1 14C]aminoisobutyric acid uptake was studied in H4IIE cultured rat hepatoma cells. Metformin enhanced both basal (from 0.213 +/- 0.016 to 0.262 +/- 0.024 nmol/mg protein, p less than 0.01) and insulin stimulated [3H] glucose incorporation into glycogen in a time-dependent and dose-dependent manner. A small effect of metformin was seen at 1 mumol/l, and its greatest effects were obtained at 10 mumol/l. At the same concentrations, metformin did not influence basal tyrosine aminotransferase activity but it potentiated insulin stimulated tyrosine aminotransferase activity (+29.2 +/- 1.4%, p less than 0.01) and prevented the loss of tyrosine-aminotransferase responsiveness to insulin in H4IIE cells desensitised by a previous exposure to insulin. In contrast, metformin had no effect on basal or insulin-stimulated [1-14C]aminoisobutyric acid uptake. Over the concentrations of metformin that enhanced insulin action in H4IIE cells, the drug had no significant effect on insulin binding to its receptor. These studies suggest, therefore, that metformin may influence cellular metabolism by potentiating certain insulin actions through mechanisms that may be beyond insulin receptor binding. PMID- 2901379 TI - Beta-adrenoceptor function in asthmatic bronchial smooth muscle. PMID- 2901380 TI - The genetically epilepsy-prone rat. AB - 1. The genetically epilepsy-prone rat (GEPR) is a valuable model for investigating mechanisms involved in epilepsy because of the controllable nature of the convulsions and their genetic origin. 2. The GEPR exhibits audiogenic seizures (AGS) and also displays higher than normal sensitivity to convulsant drugs, kindling, electroshock and hyperthermic seizures. 3. An abnormal electroencephalographic pattern and increased thresholds for auditory evoked potentials from the cochlea and brainstem are observed in the GEPR. 4. Afterdischarge-like responses and decreased sound-induced inhibition are observed in neurophysiological recordings from neurons of the inferior colliculus (IC) in the GEPR. 5. Significant deficits of norepinephrine and serotonin are observed in many regions of the GEPR brain. 6. Increases in the number of GABAergic neurons and a reduced effectiveness of iontophoretically-applied GABA are observed in the IC of this animal. 7. GABA agonists or an excitant amino acid (EAA) antagonist block AGS susceptibility when microinjected into brainstem auditory nuclei of the GEPR up to the level of IC. 8. A GABA antagonist or an EAA agonist induces susceptibility to AGS in normal rats following microinjection into IC. An increase in EAA release in IC during AGS in the GEPR is also observed. 9. This increased release of EAA and the reduced effectiveness of GABA in IC may be important seizure initiation mechanisms in the GEPR. 10. The AGS pathway in the GEPR appears to involve the auditory nuclei up to the IC as well as the brainstem reticular formation and substantia nigra but not the entopenduncular nucleus or hippocampus. PMID- 2901381 TI - Potential use of drugs modulating 5HT activity in the treatment of anxiety. AB - 1. It has been long suggested that central 5HT-mediated systems may be involved in modulation of anxiety and in the anxiolytic effect of benzodiazepines. However, recent evidence has questioned this hypothesis, particularly with respect to the mode of action of benzodiazepines. 2. Development of 5HT agonists and antagonists selective for different 5HT receptor sub-types (5HT1A, 5HT1B, 5HT2, 5HT3) has opened a new avenue for investigation of the potential role of 5HT in anxiety. 3. Buspirone is clinically active in the treatment of anxiety and it, and other anxiolytic candidates, gepirone and isapirone, may act as agonists (or perhaps partial agonists) on 5HT1A receptors. 4. The prototype 5HT1A agonist 8OH-DPAT may also have potential anxiolytic effects. 5HT1A agonists may act to suppress the activity of 5HT neurones as a major part of their action. 5. Although there is some supporting evidence, there is no clear indication of anxiolytic activity with agonists with some selectivity for 5HT1B sites (RU24969, mCPP, TMPP). 6. A selective 5HT2 antagonist, ritanserin, has anxiolytic effects in clinical studies but, like the 5HT1A agonists, does not show a similar profile to benzodiazepines in models of anxiety. 7. This raises the question of clinical predictivity of the various models used. 8. A recently developed 5HT3 antagonist, GR38032F, has been claimed to possess potential anxiolytic activity but its mode of action in this respect requires further elucidation. PMID- 2901382 TI - Droperidol enhances fentanyl and sufentanil, but not morphine, analgesia. AB - 1. The effect of droperidol pre-treatment on the analgesic potency of morphine, fentanyl and sufentanil was assessed in mice. 2. Acetic acid writhing test and tail immersion test were used to measure the analgesic response. 3. The neuroleptic augments the effects of sufentanil and fentanyl. 4. Thus, the dose response curves for fentanyl and sufentanil were shifted to the left and the ED50 of the analgesics lowered in droperidol pre-treated animals. 5. However, morphine analgesia was not influenced by droperidol. 6. The results suggest that combination of sufentanil or fentanyl with droperidol may be better than morphine to produce neuroleptanalgesia and anesthesia. PMID- 2901383 TI - Treating dental fears using nitrous oxide oxygen inhalation and systematic desensitization. PMID- 2901384 TI - Thyrotrophin-releasing hormone-induced growth hormone secretion in ducks: independence of peripheral plasma somatostatin, insulin, and glucagon. AB - In young, but not old, ducks the iv infusion of thyrotrophin-releasing hormone (TRH) markedly increased peripheral plasma growth hormone (GH) concentrations, which remained elevated throughout the 30-min period of infusion. This GH response to TRH was suppressed by the simultaneous infusion of somatostatin, which increased the level of circulating somatostatin-like immunoreactivity (SLI) to supraphysiological levels. Basal concentrations of plasma SLI in both young and old birds were suppressed by TRH infusion. Concentrations of glucagon-like immunoreactivity (GLI) were increased by the infusion of TRH in young birds but not in adults, whereas plasma immunoreactive insulin (IRI) was decreased in young birds and increased in adults following TRH infusion. These results indicate that TRH-induced GH secretion in ducks is unrelated to changes in peripheral plasma SLI, GLI, or IRI induced by TRH infusion. PMID- 2901385 TI - Genome evolution in mosquitoes: intraspecific and interspecific variation in repetitive DNA amounts and organization. PMID- 2901386 TI - The positive and negative transcriptional regulation of the Drosophila Gapdh-2 gene. AB - One of the genes encoding glyceraldehyde 3-phosphate dehydrogenase of Drosophila melanogaster, Gapdh-2, is expressed in all cell types examined, but its level of expression is regulated developmentally. Here we report the analysis of the regulatory sequences for the transcription of Gapdh-2. We have generated Gapdh-2 LacZ fusion genes in which the 5'-flanking sequence of Gapdh-2 has been mutated. Examination of the expression of these fusion genes, which have been introduced by transfection into the Schneider II cell line and by germ-line transformation into flies, led to the identification of two distinct regulatory regions, URS-1 and URS-2, within the first 145 bp of the 5'-flanking sequence of Gapdh-2. URS-1 activates transcription throughout the development of Drosophila. However, URS-2 exhibits a dual function during the development. It clearly represses transcription in Schneider II cells, and perhaps also in mid-stage embryos. In contrast, it activates transcription in larvae and adult flies. Thus, URS-2 plays a key role in the developmental regulation of Gapdh-2. Additionally, the efficient transcription of Gapdh-2 in larval and adult stages appears to depend on a synergistic function of URS-1 and URS-2. PMID- 2901387 TI - Nucleotide sequence of the gene coding for a 130-kDa mosquitocidal protein of Bacillus thuringiensis israelensis. AB - The nucleotide sequence of pVB131 containing the gene coding for a 130-kDa Bacillus thuringiensis israelensis (B.t.isr) mosquitocidal protein was determined. The pVB131 plasmid was constructed by Sekar and Carlton [Gene 33 (1985) 151-158]. Our sequencing revealed only one open reading frame large enough to code for a protein of 130 kDa. The translation start site was determined by sequencing the protein isolated from B.t.isr. The amino acid sequence of the protein was deduced from the nucleotide sequence, and its Mr was determined as 128,505. Immunological and biochemical analyses of B.t.isr mosquitocidal proteins indicated that the 130-kDa protein coded by pVB131 was indeed expressed in B.t.isr. Comparing the peptide sequence of the 130-kDa B.t.isr toxin with the sequences of other B.t. toxins having activities specific to lepidopteran species showed that several domains were highly homologous. This suggests that they are evolutionarily related to each other, and in the evolutionary process the sequences in the homologous domains that are important to the insecticidal activity have been conserved. PMID- 2901388 TI - Isolation of genes expressed in specific tissues of Arabidopsis thaliana by differential screening of a genomic library. AB - The small genome size of Arabidopsis thaliana allows the isolation of genes expressed in specific tissues and under controlled conditions by the differential screening of a genomic library, as has been shown previously for yeast and Drosophila. cDNA probes, based on poly(A)+ mRNA isolated from different Arabidopsis organs, were used in colony hybridizations with 1145 randomly chosen genomic clones, representing 27,000 kb of Arabidopsis DNA. Twenty percent of the clones containing low-copy-number sequences hybridized with one or more of the cDNA probes that were synthesized from mRNA isolated from leaves, stems, seed pods, inflorescences, callus tissue, and light-grown and dark-grown plants. Comparison of the colony hybridizations led to the identification of a large variety of clones which contain differentially expressed genes. The pattern of expression was confirmed by Northern analysis. The advantage of the described method is that it yields directly genomic sequences that contain specifically expressed or induced genes. In particular, it circumvents the construction and differential screening of cDNA libraries for every tissue or environmental parameter to be analyzed. PMID- 2901389 TI - [Objectives of the Journal with regard to the realization of the resolutions of the CPSU Central Committee and the USSR Council of Ministers: "The main trends in the development of public health and the reorganization of the public health system in the 12th five-year period and up to the year 2000"]. PMID- 2901391 TI - [A mild antibiotic for acne. Josamycin--a classic drug with new indications]. PMID- 2901390 TI - [Dale's principle and the one neuron-one transmitter concept]. AB - Dale's principle was first proposed by Eccles in 1954 based on 3 lectures given by Dale in 1934 and 1952. Many authors in the literature define Dale's principle as the "one neuron-one transmitter concept". The origin of such an idea, however, is rather vague. Neither Dale nor Eccles stated literally the one neuron-one transmitter concept. It seems now appropriate to define Dale's principle according to Eccles (1976) as follows: "at all the axonal branches of a neuron there is liberation of the same transmitter substance or substances". Recent studies showed examples that are not in accord with the "one neuron-one transmitter concept". Many cases were shown in which a neuron contains more than one transmitter. Whether this is a common rule or exceptional remains to be clarified by future studies. PMID- 2901392 TI - Hepatitis delta virus and primary hepatocellular carcinoma in Jordan. PMID- 2901393 TI - TaqI polymorphism in the LDL receptor gene and a TaqI 1.5-kb band associated with familial hypercholesterolemia. AB - The low density lipoprotein (LDL) receptor gene was analyzed in 67 unrelated healthy Japanese and 38 members of six consecutive families with familial hypercholesterolemia (FH) by Southern blot hybridization with TaqI, an LDL receptor cDNA fragment containing exons 1 to 8 being used as a probe. A new TaqI RFLP at the LDL receptor locus was detected with allele frequencies of 0.67 and 0.33. The data obtained with smaller cDNA subfragment probes revealed that the TaqI RFLP site is located within 1.1 kb of the 5' side of the EcoRI site of exon 5. The TaqI RFLP was in linkage disequilibrium with the PstI RFLP but showed no significant linkage disequilibrium with the RFLPs for AvaII, ApaLI/I15, PvuII, NcoI, and ApaLI/3'. Among the seven RFLPs at the LDL receptor locus, the TaqI RFLP was the only useful genetic marker in one of the six families with FH. Furthermore, the association of an additional TaqI 1.5-kb band with a mutant LDL receptor gene was observed in another family with FH in which the proband was homozygous for all of the seven RFLPs. The data obtained with various restriction enzymes and smaller cDNA subfragments probes suggested that a minor change in nucleotide sequences in the region including exons 5 to 8 is present in the mutant gene. These data suggest that the TaqI RFLP is a useful genetic marker at the LDL receptor locus and that TaqI serves for the analysis of some mutant LDL receptor genes, when used with small LDL receptor cDNA probes. PMID- 2901395 TI - BglII RFLPs in the COL1A2 gene in the Finnish population. PMID- 2901394 TI - Heterozygosity and localisation of normal allelic fragments for an alpha 1 antitrypsin homologous sequence. AB - Approximately 10 kb downstream of the alpha 1-antitrypsin (AAT) gene is a homologous sequence. Two polymorphisms detected with the restriction enzymes BglII and EcoRI have been reported previously. We describe two additional polymorphisms with the restriction endonucleases TaqI and HindIII and, for all four restriction enzymes, we have mapped the fragments corresponding to the normal alleles in a cosmid clone. PMID- 2901396 TI - Deletion of chromosome region 13q14 is transmissible and does not always predispose to retinoblastoma. AB - During routine screening of retinoblastoma patients for esterase D activity in red blood cell lysates a patient was identified with only 50% of normal enzyme activity. Chromosome analysis showed that this patient had a small deletion within chromosome region 13q14. Parental studies showed that, whereas the father had normal enzyme levels, the mother had esterase D levels which were also 50% of normal and a similar small 13q14 deletion. Ophthalmological examination failed to demonstrate any retinal abnormality in either parent. Thus we present the first case not only of the direct transmission of a 13q14 deletion within a family but also of an individual in whom the deletion has not predisposed to tumour formation. PMID- 2901397 TI - Allelic association of the cystic fibrosis locus and two DNA markers, XV2c and KM19, in 55 German families. AB - Allelic association between cystic fibrosis and two linked markers is demonstrated in a sample of 55 German families. It is shown by example how these observations can be used for genetic risk calculation. PMID- 2901398 TI - [Oxatomide in the therapy of urticaria]. PMID- 2901399 TI - HLA-DQ system and insulin-dependent diabetes mellitus in Japanese: does it contribute to the development of IDDM as it does in Caucasians? AB - Fifty-six unrelated Japanese patients with insulin-dependent diabetes mellitus (IDDM) were HLA-typed, and restriction fragment length polymorphism (RFLP) analysis was performed after enzyme digestion with Bam HI and Taq I by using both DR and DQ probes. As previously reported, increased frequencies of Bw54, Cw1, DR4, and DRw53, which are in strong linkage disequilibrium in the Japanese population and make the characteristic Japanese haplotype, were confirmed. DQw4, a new allele of the DQ system recognized by the monoclonal antibody HU-46 and in linkage disequilibrium with this haplotype, presented the highest IDDM association. The RFLP analysis also showed the strongest correlation to IDDM when the DQ probe was applied. These results indicate that HLA-DQ might play the most important role in the development of IDDM in Japanese as well as in Caucasians. The correlation of DQ beta amino acid sequences strongly associated with IDDM in Japanese are discussed in this study, and contrasting results were found when such sequences were compared with those of Caucasians. PMID- 2901400 TI - Genomic organization of the mouse Tla locus: study of an endogenous retroviruslike locus reveals polymorphisms related to different Tla haplotypes. AB - A retrovirus element (TLev1) is located within the Thymus leukemia antigen (Tla) locus of the C57BL/10 mouse major histocompatibility complex. Low-copy probes have been isolated from sequences flanking the TLev1 integration site to examine the distribution of TLev1 among inbred mouse strains having genotypically determined variations in TL-antigen expression. It was found that the low-copy probes cross-hybridize to regions within the Tla locus in a genotype-specific manner. Although a strong association was found between TL mouse strains and TLev1, the presence or absence of the TLev1 locus did not exclusively correlate with expression or nonexpression of TL antigens. Analysis of different Mus subspecies indicates that TLev1 integrated into a common ancestor of the species Mus musculus. It is suggested that the loss of the TLev1 locus from certain mouse genomes reflects evolutionary rearrangements in the TL region; the resulting diversity may relate to the differential expression of TL antigens among mouse strains. The probes described here provide a useful tool for examining the genomic expansions and contractions which have occurred during the evolution of the Tla locus. PMID- 2901401 TI - Mapping of the Sod-2 locus into the t complex on mouse chromosome 17. AB - A human DNA probe specific for the superoxide dismutase gene was used to identify the corresponding mouse gene. Under the chosen hybridizing conditions, the probe detected DNA fragments most likely carrying the mouse Sod-2 gene. Mapping studies revealed that the Sod-2 gene resides in the proximal inversion of the t complex on mouse chromosome 17. All complete t haplotypes tested showed restriction fragment length polymorphism which is distinct from that found in all wild-type chromosomes tested. The Sod-2 locus maps in the same region as some of the loci that influence segregation of t chromosomes in male gametes. The possibility that the Sod-2 locus is related to some of the t-complex distorter or responder loci is discussed. The data indicate that the human homolog of the mouse t complex has split into two regions, the distal region remaining on the p arm of human chromosome 6, while the proximal region has been transposed to the telomeric region of this chromosome's q arm. PMID- 2901402 TI - Attachment of Escherichia coli via mannose- or Gal alpha 1----4Gal beta containing receptors to human colonic epithelial cells. AB - The role of bacterial adhesion for the maintenance of the large-intestinal microflora has not been established. In this study, colonic cells from the adenocarcinoma cell line HT-29 or from surgical specimens were tested for the ability to bind Escherichia coli. The E. coli strains were manipulated by transformation or by mutagenesis to express either mannose-specific type 1 fimbriae (strains 506 MS and HU742) or Gal alpha 1----4Gal beta-specific P fimbriae (506 MR and HU824). Binding to HT-29 cells was seen with strains of either receptor specificity and was inhibited by alpha-methyl mannoside or globotetraosylceramide (GalNAc beta 1----3Gal alpha 1----4Gal beta 1----4Glc ceramide), respectively. The Gal alpha 1----4Gal beta-specific strains interacted with a loosely surface-associated substance, which was sensitive to mechanical treatment and incubation at 37 degrees C, while the mannose-specific strains bound both directly to the cell and to the loosely associated substance. Isolated colonic epithelial cells bound the mannose-specific bacteria in high numbers, while the attachment of the Gal alpha 1----4Gal beta-specific strains depended on the elution method. Cells eluted sequentially with magnetic stirring were unable to bind the Gal alpha 1----4Gal beta-specific bacteria, while elution by a more gentle method resulted in binding of these strains to material loosely associated with the epithelial cells. Thus, the binding pattern of isolated colonic epithelial cells paralleled that of the HT-29 cell line. Conceivably, binding to mannose- and Gal alpha 1----4Gal beta-containing receptors could contribute to the maintenance of E. coli in the human large intestine. PMID- 2901403 TI - Isolation and comparison of Escherichia coli strains from canine and human patients with urinary tract infections. AB - We analyzed Escherichia coli strains isolated from dogs with urinary tract infections (UTIs) in an attempt to determine if any of these strains were similar to E. coli isolated from humans with UTIs. Using genotypic and phenotypic traits, we identified four canine and six human E. coli UTI isolates that all appeared to be closely related or identical. All isolates shared similar DNA sequences for pyelonephritis-associated pili (pap), alpha-hemolysin (hly), and insertion sequence 5 (IS5), on the basis of Southern blot analysis. Similar outer membrane protein, pilin, and plasmid profiles were obtained for each of the isolates, although minor heterogeneity was observed. All of these isolates expressed a neuraminidase-sensitive binding phenotype in contrast to the majority of human isolates, which are known to express an adhesin that recognizes terminal digalactoside residues. Taken together, these results suggest that similar E. coli uropathogens may be capable of infecting both dogs and humans. To determine if the intestinal tracts of dogs were a reservoir for uropathogenic E. coli, eight paired rectal and urine pap+ E. coli strains were cultured from dogs with UTIs. By using the same genotypic and phenotypic criteria described above as a basis for strain identity, seven of eight urine-rectal pairs showed intrapair identity. However, each urine-rectal pair displayed a unique overall profile and could be distinguished from the other pairs. We conclude that the uropathogen colonizing the bladders of dog can also be the predominant strain colonizing the intestinal tracts. PMID- 2901404 TI - Binding characteristics of Escherichia coli adhesins in human urinary bladder. AB - We studied domains in the human bladder that acted as receptors for Escherichia coli P, S, type 1, type 1C, and O75X fimbriae or adhesin and domains in the human kidneys that were receptors for E. coli type 1C fimbriae. Binding sites in frozen tissue sections were localized by direct staining with fluorochrome-labeled recombinant strains and by indirect immunofluorescence with the purified adhesins. In the bladder, the P and S fimbriae showed closely similar binding to the epithelial and muscular layers, and the S fimbriae also bound to the connective tissue elements. Type 1 fimbriae bound to vascular walls and to muscle cells, whereas the O75X adhesin bound avidly to connective tissue elements and to some extent to epithelial and muscle cells of the bladder. The type 1C fimbriae bound to distal tubules and collecting ducts of the kidney and to vascular endothelial cells in both the kidney and bladder. The binding of all adhesin types was inhibited by specific receptor analogs or Fab fragments. The results reveal a possible mechanism by which the type 1C fimbriae may help invasion of E. coli in the kidneys but do not support a pathogenetic role for type 1 fimbriae. Similar tissue specificity of P and S fimbriae in the human urinary tract indicates that the presence of binding sites on uroepithelia does not fully explain the virulence properties of P fimbriae in human urinary tract infections. PMID- 2901406 TI - Catecholamine synthesis in Ascaridia galli (Nematoda) PMID- 2901405 TI - Identification of factors in human urine that inhibit the binding of Escherichia coli adhesins. AB - Earlier studies on the binding of Escherichia coli adhesins to the human urinary tract have indicated that the ability to recognize binding sites on the urinary tract epithelial cells is not a characteristic for P fimbriae only, but is also shared by some other adhesins that are not associated with pyelonephritis, especially S fimbriae. In the present study we have investigated whether human urine contains inhibitors of the binding of E. coli adhesins. Normal human urine was found to inhibit hemagglutination by S and type 1 fimbriae but not P fimbriae. The major inhibitor of S fimbriae in normal urine was identified as Tamm-Horsfall glycoprotein, and the interaction with S fimbriae is probably mediated by its sialyloligosaccharide chains. No significant variation was observed in the inhibitory effect of T-H glycoprotein preparations originating from different individuals. In contrast to S fimbriae, the major inhibitors of type 1 fimbriae in urine were identified as low-molecular-weight compounds. Gel filtration and ion-exchange chromatography and alpha-mannosidase treatment indicated that they were neutral alpha-mannosides, probably manno oligosaccharides with three to five saccharides. Studies of urine samples collected from several individuals indicated the common occurrence of these inhibitory alpha-mannosides. Type 1 fimbriae bound to immobilized T-H glycoprotein, but, unlike S fimbriae, their binding was poorly inhibited by soluble T-H glycoprotein. Some urine samples were also found to contain low molecular-weight inhibitors for the O75X adhesin of E. coli. These results emphasize that to function as a virulence factor in human urinary tract infections, an adhesin must evidently recognize such receptor structures at the infection sites that are not excreted in soluble form in urine. This prerequisite is filled by P fimbriae but not by type 1 or S fimbriae. PMID- 2901407 TI - Treatment of anxiety associated with electrophysiologic studies. AB - Programmed electrical stimulation, also known as electrophysiologic studies (EPS), is a cardiologic technique used to help guide physicians in their management of selected patients with cardiac arrhythmias. Data are presented for 14 consecutive patients undergoing EPS seen in psychiatric consultation who had a diagnosis related to anxious mood. Successful management strategies, which evolved from work with these patients, included psychologic approaches (supportive psychotherapy and education) and psychopharmacologic agents (most commonly alprazolam). EPS and related physiologic aspects of anxiety and stress are briefly reviewed. PMID- 2901408 TI - Mapping of a restriction fragment length polymorphism associated with defective DR beta 4 chain expression to the HLA-DRB1 gene. AB - The HLA-DR beta 4 chain, encoded by the DRB4 gene, carries two DRw53 determinants normally expressed by DR4, DR7, and DR9 individuals. However, some DR7 individuals (DR7, Dw11) fail to express the DR beta 4 chain. At the genomic level, a HindIII restriction fragment length polymorphism can be detected in these individuals with a DR beta cDNA probe. The association of this altered HindIII fragment with defective beta 4 chain expression suggested the possibility that the polymorphic fragment was derived from the DRB4 gene and might, therefore, be related to the defect in expression. However, detailed Southern blot analysis has now mapped the polymorphic fragment to the 3' end of the DRB1 gene, approximately 100 kb away from the defective DRB4 gene. Although the alteration in the DRB1 gene might involve sequences important in regulating the expression of the DRB4 gene, it is more likely that the association results from strong positive linkage disequilibrium between these DR beta chain genes. PMID- 2901409 TI - Intraabdominal retraction and entrapment of testicle associated with indirect inguinal hernia. AB - A 19-year-old man presented with an acute retraction and entrapment of the left testicle into the abdomen through an indirect inguinal hernia. No previous case reports were found in the literature. The evaluation and treatment of the disappearing or absent testicle are briefly reviewed. PMID- 2901410 TI - 3'-O-(5-fluoro-2,4-dinitrophenyl)ADP ether and ATP ether. Affinity reagents for labeling ATPases. AB - The affinity reagents 3'-O-(5-fluoro-2,4-dinitrophenyl)ADP ether (FDNP-ADP) and 3'-O-(5-fluoro-2,4-dinitrophenyl)ATP ether (FDNP-ATP) were synthesized and characterized. FDNP[14C]ADP was found to label the active site of mitochondrial F1-ATPase slowly at room temperature but with high specificity. F1 was effectively protected from the labeling reagent by ATP or ADP. An average number of 1.3 covalent label per F1 is sufficient for 100% inhibition of the ATPase. About 73% of the radioactive label was found covalently attached to beta subunits, 9% on alpha, practically none on gamma, delta, and epsilon. Cleavage of the labeled enzyme by pepsin and sequencing of the major radioactive peptide showed that the labeled amino acid residue in beta subunit was Lys beta 162. These results show that Lys beta 162 is indeed at the active site of F1 as assumed in the recently proposed models (Fry, D. C., Kuby, S. A., and Mildvan, A. S. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 907-911; Duncan, I. M., Parsonage, D., and Senior, A. E. (1986) FEBS Lett. 208, 1-6). PMID- 2901411 TI - Mutational analysis of domain I of Pseudomonas exotoxin. Mutations in domain I of Pseudomonas exotoxin which reduce cell binding and animal toxicity. AB - Pseudomonas exotoxin (PE) is a single polypeptide chain that contains 613 amino acids and is arranged into three structural domains. Domain I is responsible for cell recognition, II for translocation of PE across membranes and III for ADP ribosylation of elongation factor 2. Treatment of PE with reagents that react with lysine residues has been shown to lead to a reduction in cytotoxic activity apparently due to a modification of domain I (Pirker, R., FitzGerald, D. J. P., Hamilton, T. C., Ozols, R. F., Willingham, M. C., and Pastan, S. (1985) Cancer Res. 45, 751-757). To determine which lysine residues are important in cell recognition, all 12 lysines in domain I were converted to glutamates by site directed mutagenesis. Also, two deletion mutants encompassing almost all of domain I (amino acids 4-252) or most of domain I (amino acids 4-224) were studied. The mutant proteins were produced in Escherichia coli, purified, and tested for their cytotoxic activity against Swiss 3T3 cells and in mice. The data indicate that conversion of lysine 57 to glutamate reduces cytotoxic activity towards 3T3 cells 50-100-fold and in mice about 5-fold. Deletion of amino acids 4 224 causes a similar reduction in toxicity towards cells and mice. Deletion of most of the rest of domain I (amino acids 4-252) causes a further reduction in toxicity toward cells and mice indicating this second region between amino acids 225 and 252 of domain I is also important in the toxicity of PE. Competition assays indicated that the ability of PEGlu57 to bind to 3T3 cells was greatly diminished, accounting for its diminished cytotoxic activity. PMID- 2901412 TI - Transport-deficient mutations in the low density lipoprotein receptor. Alterations in the cysteine-rich and cysteine-poor regions of the protein block intracellular transport. AB - Certain individuals with familial hypercholesterolemia (FH) produce mutant forms of the low density lipoprotein (LDL) receptor that fail to move from the endoplasmic reticulum to the Golgi complex. Here, we describe the cloning and expression of one such mutant allele, FH 429. The mutation causes a substitution of a Val for a Gly at residue 544. When recreated in an expressible cDNA, this substitution gives rise to an LDL receptor that is not transported to the cell surface and is rapidly degraded. Three previously mapped transport-deficient alleles of the LDL receptor were traced to the cysteine-rich repeats of the protein, suggesting that the generation of non-disulfide-bonded (free) cysteines might cause the block in transport. The FH 429 mutation is not located in a cysteine-rich region, however. We have attempted to test the role of cysteine by expressing mutant cDNAs that encode proteins blocked in transport and predicted to contain free cysteines. The results suggest that free cysteines are not obligatory for the blocked intracellular movement of mutant LDL receptors. PMID- 2901413 TI - Bordetella pertussis adenylate cyclase. Identification of multiple forms of the enzyme by antibodies. AB - Two forms of Bordetella pertussis adenylate cyclase of 200 and 47 kDa have been purified from dialyzed urea extract of the bacteria to specific activities of 466 and 1685 mumol.min-1.mg-1, respectively. Both forms are activated 50-200-fold by calmodulin. The half-maximum concentration required for the activation of the 200 kDa catalyst is 5.4.10(-9) M, whereas the one required for activation of the 47 kDa catalyst is 1.8.10(-10) M. Polyclonal antibodies raised against the 47-kDa catalyst specifically recognize both forms of the enzyme in purified state as well as in bacterial extracts on immunoblots. The antibody inhibits at similar titer adenylate cyclase activity of the purified forms as well as the activity present in dialyzed urea extract of the bacteria. It also prevents the penetration of the invasive B. pertussis adenylate cyclase into human lymphocytes. The inhibition induced by the antisera is specific to B. pertussis enzyme, since both calmodulin-dependent brain and sperm adenylate cyclase are not affected by the antibody. PMID- 2901414 TI - Glucagon gene expression in vertebrate brain. AB - An increasing number of regulatory peptide genes are known to be transcribed in neuroendocrine cells of the intestine and neurons of the central and peripheral nervous system. The discovery of the expression of peptide hormone genes in the nervous system has led to the suggestion that these peptides may function as neurotransmitters, neuromodulators, and releasing or inhibiting factors in different regions of the brain. Glucagon and the glucagon-like peptides are derived from proglucagon in the pancreatic islets and intestine. A role for these peptides in the central nervous system has been proposed, but evidence for the biosynthesis of proglucagon in brain has been lacking. We now report that the glucagon gene is expressed in the brainstem and hypothalamus and that a glucagon mRNA transcript identical to that produced in pancreas and intestine gives rise to proglucagon-related peptides in the brain. PMID- 2901415 TI - The kinetic mechanism of beef kidney D-aspartate oxidase. AB - The mechanism of action of the flavoprotein D-aspartate oxidase (EC 1.4.3.1) has been investigated by steady-state and stopped flow kinetic studies using D aspartate and O2 as substrates in 50 mM KPi, 0.3 mM EDTA, pH 7.4, 4 degrees C. Steady-state results indicate that a ternary complex containing enzyme, O2, and substrate (or product) is an obligatory intermediate in catalysis. The kinetic parameters are turnover number = 11.1 s-1, Km(D-Asp) = 2.2 x 10(-3) M, Km(O2) = 1.7 x 10(-4) M. Rapid reaction studies show that 1) the reductive half reaction is essentially irreversible with a maximum rate of reduction of 180 s-1; 2) the free reduced enzyme cannot be the species which is reoxidized during turnover since its reoxidation by oxygen (second order rate constant equal to 5.3 x 10(2) M-1 s-1) is too slow to be of relevance in catalysis; 3) reduced enzyme can bind a ligand rapidly and be reoxidized as a complex at a rate faster than that observed for the free reduced enzyme; 4) the rate of reoxidation of reduced enzyme by oxygen during turnover is dependent on both O2 and D-aspartate concentrations (second order rate constant of reaction between O2 and reduced enzyme-substrate complex equal to 6.2 x 10(4) M-1 s-1); and 5) the rate-limiting step in catalysis occurs after reoxidation of the enzyme and before its reduction in the following turnover. A mechanism involving reduction of enzyme by substrate, dissociation of product from reduced enzyme, binding of a second molecule of substrate to the reduced enzyme, and reoxidation of the reduced enzyme-substrate complex is proposed for the enzyme-catalyzed oxidation of D aspartate. PMID- 2901416 TI - A novel type of short- and medium-chain acyl-CoA hydrolases in brown adipose tissue mitochondria. AB - Acyl-CoA hydrolase activities were studied in brown adipose tissue from hamsters. A latent activity was observed in isolated mitochondria. Two peaks of activity were clearly visible in mitochondria, one with an optimum at propionyl-CoA ("short-chain hydrolase") and one with an optimum at nonanoyl-CoA ("medium-chain hydrolase"); there was only low activity toward palmitoyl-CoA and longer-chain acyl-CoAs. In subcellular fractionation experiments, the activity of the short chain and the medium-chain hydrolase fully followed that of the mitochondrial matrix marker enzyme 2-oxoglutarate dehydrogenase. The specific activity of the hydrolases in the mitochondrial fraction was doubled after cold acclimation. beta NADH inhibited the short- and medium-chain hydrolases; alpha-NADH, NADPH, and NAD+ were without effect. ADP stimulated the short- and medium-chain hydrolases; ATP and AMP were practically without effect. Evidence is presented to indicate that NADH and ADP interact on the enzyme at the same site and that ADP is essential for the maintenance of the short- and medium-chain enzyme activities. A positive effect of KCl was found on the short- and medium-chain hydrolase activities. Also, the divalent ions Ca2+ and Mg2+ were stimulatory, but only Ca2+ was able to overcome NADH inhibition, possibly due to interaction directly with NADH. It is concluded that brown adipose tissue mitochondria, besides a conventional type of acyl-CoA hydrolase, contain two species of a novel type of acyl-CoA hydrolases which are characterized by being regulated by ADP and NADH (interacting at a common site) and by having an obligatory requirement for ADP. PMID- 2901417 TI - ADP-ribosylated actin caps the barbed ends of actin filaments. AB - The mode of action on actin polymerization of skeletal muscle actin ADP ribosylated on arginine 177 by perfringens iota toxin was investigated. ADP ribosylated actin decreased the rate of nucleated actin polymerization at substoichiometric ratios of ADP-ribosylated actin to monomeric actin. ADP ribosylated actin did not tend to copolymerize with actin. Actin filaments were depolymerized by the addition of ADP-ribosylated actin. The maximal monomer concentration reached by addition of ADP-ribosylated actin was similar to the critical concentration of the pointed ends of actin filaments. ADP-ribosylated actin had no effect on the rate of polymerization of gelsolin-capped actin filaments which polymerize at the pointed ends. The results suggest that ADP ribosylated actin acts as a capping protein which binds to the barbed ends of actin filaments to inhibit polymerization. Based on an analysis of the depolymerizing effect of ADP-ribosylated actin, the equilibrium constant for binding of ADP-ribosylated actin to the barbed ends of actin filaments was determined to be about 10(8) M-1. As actin is ADP-ribosylated by perfringens iota toxin and by botulinum C2 toxin, it appears that conversion of actin into a capping protein by ADP-ribosylation is a pathophysiological reaction catalyzed by bacterial toxins which ultimately leads to inhibition of actin assembly. PMID- 2901418 TI - Studies of the phosphoenzyme intermediate of the yeast plasma membrane proton translocating ATPase. AB - The yeast plasma membrane proton-pumping ATPase forms a phosphorylated intermediate during the hydrolysis of ATP. The fraction of enzyme phosphorylated during steady-state ATP hydrolysis was studied as a function of substrate concentration (MgATP), Mg2+ concentration, and pH. The dependence of the fraction of enzyme phosphorylated on the concentration of MgATP is sigmoidal, and the isotherms can be fit with parameters and mechanisms similar to those used to describe ATP hydrolysis. The isotherm is significantly more sigmoidal at pH 5.5 than at pH 6.0, with the limiting percentage (100.mol of phosphate/mol of enzyme) of enzyme phosphorylated being 70% and 6%, respectively, at the two pH values. The maxima in the steady-state rate of ATP hydrolysis occur at higher concentrations of Mg2+ and higher pH than the maxima in the fraction of enzyme phosphorylated. This suggests that the rate-determining step for ATP hydrolysis is different from that for enzyme phosphorylation and the hydrolysis of phosphoenzyme is enhanced by Mg2+ and high pH. The rate of phosphoenzyme formation was investigated with the quenched-flow method, but only a lower bound of 140 s-1 could be obtained for the rate constant at MgATP concentrations greater than 2.5 mM. Since the turnover number for ATP hydrolysis under similar conditions is 14 s-1, the rate-determining step in ATP hydrolysis occurs after enzyme phosphorylation. PMID- 2901419 TI - Transcriptional regulation of the leukocyte adherence protein beta subunit during human myeloid cell differentiation. AB - Adherence reactions involving human leukocytes are mediated by a family of glycoprotein surface antigens composed of three different alpha subunits designated alpha L, alpha M, and alpha X, each of which is associated with a single beta subunit in an alpha 1 beta 1 heterodimer structure. We cloned the cDNA for the common beta subunit and investigated beta subunit mRNA expression in HL-60 promyelocytic leukemia cells and human granulocytic cells. Leukocyte adherence receptor beta subunit mRNA transcripts were present in low levels in HL 60 myeloblasts and promyelocytes and increased 10-fold or greater with chemically induced differentiation to more mature granulocytes (using retinoic acid and dimethylformamide) or monocyte/macrophages (using phorbol myristate acetate). Levels of beta subunit mRNA expression were also increased both in normal human peripheral blood granulocytes and in granulocytes from patients with chronic myelogenous leukemia. Nuclear run-off assays indicated that the increased steady state level of the beta subunit mRNA in retinoic acid-differentiated HL-60 cells was secondary to enhanced beta subunit gene transcription. We conclude that mRNA levels for the beta subunit of the receptor on human leukocytes that mediates cellular adherence are increased in more mature granulocytic cells compared to immature myeloid precursors and that this enhanced mRNA expression is transcriptionally regulated. PMID- 2901420 TI - High-pressure water-gun injection injuries to the extremities. A report of six cases. AB - High-pressure water-gun injection injuries are different from injection injuries that are caused by other agents, in that they are associated with extensive subcutaneous emphysema but only slight soft-tissue inflammation or destruction. The cases of six patients who had such an injury were reviewed. It was found that local irrigation and debridement, together with a short course of penicillin or a broad-spectrum cephalosporin, resulted in complete recovery from this relatively benign variant of high-pressure injection injury. PMID- 2901421 TI - The UGI series in renal transplant candidates. AB - We reviewed the charts of 115 renal transplant recipients who had pre-transplant upper gastrointestinal (UGI) barium examinations to assess this examination as a predictor of post-transplant ulceration and hemorrhage. In the past surgical therapy for peptic ulcers was recommended before transplantation because of the risk of life-threatening hemorrhage after transplantation. Peptic ulcer disease was found in 22 patients. Fifteen of these were treated with histamine H2 receptor antagonists and none had ulceration post-transplantation. Three of the seven not so treated had recurrent peptic ulceration. The other 93 examinations were normal. Twelve of the patients with normal examinations developed post transplant peptic ulceration. We conclude that: (a) the pre-transplant UGI series may not distinguish those patients at risk of UGI ulceration post-transplantation and (b) treatment with H2-receptor antagonists obviates the need for surgical therapy of peptic ulcer disease in these patients before transplantation. PMID- 2901423 TI - Development of macrociliary cells in Beroe. I. Actin bundles and centriole migration. AB - Differentiation of macrociliary cells on regenerating lips of the ctenophore Beroe was studied by transmission electron microscopy. In this study of early development, we found that basal bodies for macrocilia arise by an acentriolar pathway near the nucleus and Golgi apparatus, in close association with plaques of dense fibrogranular bodies. Procentrioles are often aligned side-by-side in double layers with the cartwheel ends facing outward toward the surrounding plaques of dense granules. Newly formed basal bodies then disband from groups and develop a long striated rootlet at one end. At the same time, an array of microfilaments arises in the basal cytoplasm. The microfilaments are arranged in parallel strands oriented toward the cell surface. The basal body-rootlet units are transported to the apical surface in close association with the assembling actin filament bundle. Microfilaments run parallel to and alongside the striated rootlets, to which they often appear attached. Basal body-rootlet units migrate at the heads of trails of microfilaments, as if they are pushed upwards by elongation of their attached actin filaments. Near the apical surface the actin bundle curves and runs below the cell membrane. Newly arrived basal body-rootlets tilt upwards out of the microfilament bundle to contact the cell membrane and initiate ciliogenesis. The basal bodies tilt parallel to the flat sides of the rootlets, and away from the direction in which the basal feet point. The actin bundle continues to enlarge during ciliogenesis. These results suggest that basal body migration may be driven by the directed assembly of attached actin filaments. PMID- 2901422 TI - Identification of peroxisomal targeting signals located at the carboxy terminus of four peroxisomal proteins. AB - As part of an effort to understand how proteins are imported into the peroxisome, we have sought to identify the peroxisomal targeting signals in four unrelated peroxisomal proteins: human catalase, rat hydratase:dehydrogenase, pig D-amino acid oxidase, and rat acyl-CoA oxidase. Using gene fusion experiments, we have identified a region of each protein that can direct heterologous proteins to peroxisomes. In each case, the peroxisomal targeting signal is contained at or near the carboxy terminus of the protein. For catalase, the peroxisomal targeting signal is located within the COOH-terminal 27 amino acids of the protein. For hydratase:dehydrogenase, D-amino acid oxidase, and acyl-CoA oxidase, the targeting signals are located within the carboxy-terminal 15, 14, and 15 amino acids, respectively. A tripeptide of the sequence Ser-Lys/His-Leu is present in each of these targeting signals as well as in the peroxisomal targeting signal identified in firefly luciferase (Gould, S.J., G.-A. Keller, and S. Subramani. 1987. J. Cell Biol. 105:2923-2931). When the peroxisomal targeting signal of the hydratase:dehydrogenase is mutated so that the Ser-Lys-Leu tripeptide is converted to Ser-Asn-Leu, it can no longer direct proteins to peroxisomes. We suggest that this tripeptide is an essential element of at least one class of peroxisomal targeting signals. PMID- 2901424 TI - Development of macrociliary cells in Beroe. II. Formation of macrocilia. AB - Two patterns of macrociliary growth occur in Beroe. Early differentiation described previously (Tamm & Tamm, 1988) leads to the first pattern of ciliogenesis. A tuft of 10-20 single cilia initially grows out from basal bodies that have migrated to the cell surface and are axially aligned. Ciliary membranes then begin to fuse along their length, except at the base, resulting in thicker groups of cilia on each cell. Progressive fusion of ciliary membranes, together with addition and elongation of new axonemes, finally results in mature macrocilia, 5 microns thick and 40 microns long, enclosed by a single membrane distally. The second pattern of ciliogenesis begins with the simultaneous appearance of several hundred ciliary buds on the apical surface. The short cilia possess individual membranes with bulbous tips, and are not axially aligned. Subsequent elongation is accompanied by progressive fusion of neighbouring ciliary membranes, except at the base, leading to flat-topped 'stumps' surrounded by a single membrane distally. Further elongation then proceeds asymmetrically within each stump. Axonemes on the aboral side of the macrocilium stop elongating, while those towards the oral side increase progressively in height, resulting in a slanted profile. Basal feet and central-pair microtubules are now uniformly aligned. Unequal elongation of axonemes on the oral and aboral sides of the macrocilium continues until the macrocilium resembles a lobster's claw, with a long slender shaft projecting from a broad base. Finally, the polarity of unequal growth reverses: the shorter axonemes on the aboral side elongate and almost catch up with the longer ones on the opposite side, resulting in a mature macrocilium of uniform diameter. The unusual membrane architecture of the macrocilium is thus a consequence of selective fusion of the distal regions of originally separate ciliary membranes. The polarized, asymmetrical growth of axonemes on the two sides of the macrocilium illustrates a remarkable control of microtubule elongation at the subcellular level. PMID- 2901425 TI - Focal cerebral ischaemia in the cat: treatment with the glutamate antagonist MK 801 after induction of ischaemia. AB - The effects of the glutamate N-methyl-D-aspartate receptor antagonist MK-801 in reducing ischaemic brain damage have been examined in anaesthetised cats, with drug treatment being initiated 2 h after the induction of cerebral ischaemia. Focal cerebral ischaemia was produced by permanent occlusion of one middle cerebral artery, and the animals were killed 6 h later. The amount of early irreversible ischaemic damage was assessed at 16 predetermined stereotactic planes. Treatment with MK-801 (5 mg/kg, i.v.) 2 h after middle cerebral artery occlusion reduced significantly the volume of ischaemic damage (from 1,625 +/- 384 mm3 of the cerebral hemisphere in vehicle-treated cats to 792 +/- 385 mm3 in MK-801-treated cats). The demonstration of reduced ischaemic brain damage with MK 801, when the agent is administered after the induction of ischaemia, extends the therapeutic potential of such agents in the treatment of focal cerebral ischaemia in humans. PMID- 2901427 TI - The neurobiology of infantile autism. PMID- 2901426 TI - CRH defects in Alzheimer's and other neurologic diseases. PMID- 2901428 TI - Thyrotropin (TSH) receptor modulation by specific TSH receptor antibodies in Graves' disease. AB - In Graves' disease (GD), an antireceptor autoantibody disease, individual variability in the pathogenic interaction between TSH receptors and autoantibodies has been reported. This variability can be due to allotypic (person to person) variability in the receptors or differences in autoantibody amount or specificity. This fundamental issue was investigated by evaluating immunoglobulin G (Ig)-induced TSH receptor modulation in thyroid tissue from 19 patients with GD. TSH receptor modulation by Graves' Ig was defined as the appearance of 1 class of high affinity binding sites, instead of the usual 2 classes of binding sites. Ig-induced modulation of receptors occurred in 9 of 19 (47%) experiments with autologous (patient's own) tissues and correlated with the presence of TSH receptor antibodies, measured as TSH binding inhibitor Igs. Of these 9 receptor-modulating Graves' Ig preparations, 7 (78%) also had a receptor modulating effect in other patient's (homologous) thyroid tissue. Nine of the 10 Graves' Ig preparations that were negative for TSH receptor-modulating activity in autologous thyroid tissue were tested with other patients' thyroid tissues; 7 (78%) were negative, and all were TSH binding inhibitor Ig negative. We conclude that variability in the occurrence of TSH receptor modulation was associated with the presence or absence of TSH-binding inhibitor Ig. No evidence for allotypic differences in TSH receptors in GD was found. PMID- 2901429 TI - Detection of the thyroxine-binding globulin (TBG) gene in six unrelated families with complete TBG deficiency. AB - T4-binding globulin (TBG) is a glycoprotein of hepatic origin which transports thyroid hormone in serum. Inherited TBG defects in man are X-chromosome linked and are expressed in hemizygotes as complete deficiency, partial deficiency, or excess. Since TBG is not necessary for thyroid hormone action, affected subjects are healthy. Using DNA probes for human TBG, we searched for restriction fragment length polymorphisms in six affected males belonging to 6 unrelated families with inherited complete TBG deficiency and an equal number of normal males. TBG could not be detected in the serum of any of the TBG-deficient males by a specific and sensitive RIA capable of detecting as little as 5 micrograms TBG/L or 0.031% of the average normal serum TBG concentration. DNA isolated from white blood cells was digested with 11 restriction endonucleases, and the digests were submitted to DNA blot analysis using two cloned TBG-DNA probes which together covered the entire protein coding and the 5'-flanking sequences of the TBG gene. A total of 26 different bands were detected on DNA blots, identifying 18 restriction sites located within the 4.2-kilobase TBG gene, which includes intronic, exonic, and 5' flanking sequences. This analysis, which sampled 2.3% of the total TBG genome, failed to reveal differences in fragment size among the 6 TBG-deficient and 6 normal males examined. One restriction endonuclease (NcoI) identified normal sequences at the putative promoter region of the gene, and four other endonucleases (TaqI, SstII, MspI, and HpaII) recognized the cytosine-guanine dinucleotide phosphate sequences representing potential mutation hot spots. Although C was methylated at these sites, no C to T (thymidine) transitions were found. These data suggest that large deletions, insertions, or rearrangements of the TBG gene, or mutations at sites of methylated cytosine-guanine dinucleotide phosphate dimers are not common mechanisms for inherited complete TBG deficiency in man. PMID- 2901430 TI - Medullary thyroid carcinoma: prognosis of familial versus sporadic disease and the role of radiotherapy. AB - A retrospective study of 202 patients with medullary thyroid carcinoma (MTC) diagnosed between 1943 and 1987 was done to compare the prognosis of patients with sporadic disease and those with the familial form of multiple endocrine neoplasia type II and to study the effect of radiotherapy. Patients with multiple endocrine neoplasia type II had a significantly higher survival rate than did patients with the sporadic variety (P less than 0.005), but most patients with sporadic tumors were older and had more advanced disease. No differences in survival rates were found when patients from these 2 groups were matched for age and involvement of the thyroid gland only (P greater than 0.3), involvement of the thyroid gland plus cervical nodes (P greater than 0.3), and involvement of the thyroid gland, cervical nodes, and soft tissue (P greater than 0.7). When patients with MTC who received radiotherapy were matched for age, extent of disease, and surgery with patients who had had no radiotherapy, the latter group was found to live significantly longer (P less than 0.05). We conclude that 1) the apparently poor prognosis of patients with the sporadic variety of MTC may be related to the patients' older age at detection rather than to inherent differences in the two forms of disease, and 2) radiotherapy has little effect on MTC. PMID- 2901431 TI - Reciprocal regulation of antral gastrin and somatostatin gene expression by omeprazole-induced achlorhydria. AB - Gastric acid exerts a feedback inhibition on the secretion of gastrin from antral G cells. This study examines whether gastrin gene expression is also regulated by changes in gastric pH. Achlorhydria was induced in rats by the gastric H+/K+ ATPase inhibitor, omeprazole (100 mumol/kg). This resulted in fourfold increases in both serum gastrin (within 2 h) and gastrin mRNA levels (after 24 h). Antral somatostatin D cells probably act as chemoreceptors for gastric acid to mediate a paracrine inhibition on gastrin secretion from adjacent G cells. Omeprazole induced achlorhydria reduced D-cell activity as shown by a threefold decrease in antral somatostatin mRNA levels that began after 24 h. Exogenous administration of the somatostatin analogue SMS 201-995 (10 micrograms/kg) prevented both the hypergastrinemia and the increase in gastrin mRNA levels caused by omeprazole induced achlorhydria. Exogenous somatostatin, however, did not influence the decrease in antral somatostatin mRNA levels seen with achlorhydria. These data, therefore, support the hypothesis that antral D cells act as chemoreceptors for changes in gastric pH, and modulates somatostatin secretion and synthesis to mediate a paracrine inhibition on gastrin gene expression in adjacent G cells. PMID- 2901432 TI - Catabolic rate of low density lipoprotein is influenced by variation in the apolipoprotein B gene. AB - This study examines the potential influence of genetic variation on the metabolism of LDL. Restriction fragment length polymorphisms (RFLP) of the gene coding for apo B were identified using the endonucleases Xba I, Eco RI, and Msp I in a group of 19 subjects with moderate hyperlipidemia. There was a significant association between the Xba I polymorphism and the total fractional clearance rate (FCR) of LDL. The individuals with the X1X1 genotype had, on average, a 22% higher FCR (P less than 0.025) than those with the genotype X2X2 (X2 allele = presence of Xba I cutting site). This difference was attributable to increased clearance by the receptor-mediated pathway of LDL catabolism. In this group of subjects, there was no association of LDL kinetic parameters and RFLPs of the LDL receptor gene or the AI- CIII- AIV gene cluster. The data suggest that variation in apo B itself, presumably acting through variable binding to the LDL receptor, makes a significant contribution to the rate of catabolism of LDL. PMID- 2901433 TI - Catecholamine effects upon rat hypothalamic corticotropin-releasing hormone secretion in vitro. AB - To further our understanding of the functional role of catecholaminergic systems in regulating hypothalamic corticotropin-releasing hormone (CRH) secretion, we assessed the direct effects of a multiplicity of catecholamine agonists and antagonists on hypothalamic CRH secretion. To accomplish this, we used an in vitro rat hypothalamic organ culture system in which CRH secretion from single explants was evaluated by a specific RIA (IR-rCRH). Norepinephrine (NE) stimulated IR-rCRH secretion dose dependently, with peak effects in the nanomolar range. The effect of NE was antagonized by the mixed alpha antagonist phentolamine, the alpha 1 antagonist prazosin, and the alpha 2 antagonist yohimbine, but not by the beta blocker, L-propanolol. Compatible with these data were the findings that the alpha 1 agonist phenylephrine and the alpha 2 agonist clonidine both stimulated IR-rCRH secretion in a dose-dependent fashion. On the other hand, whereas the beta agonist, isoproterenol, caused a weak, non-dose dependent increase in IR-rCRH secretion, this effect could not be antagonized by L-propanolol. Despite pretreatment with serotonin and acetylcholine antagonists, the effect of NE upon IR-rCRH secretion was undiminished, suggesting that NE induced CRH secretion is not mediated by either neurotransmitter. On the other hand, pretreatment with gamma-aminobutyric acid (GABA) attenuated NE-induced IR rCRH secretion. Whereas epinephrine (E) stimulated IR-rCRH secretion, this occurred only at higher concentrations, and was antagonized by phentolamine, but not by L-propanolol. Dopamine (DA) had a weak stimulatory effect that could be antagonized by the DA1 receptor antagonist, SCH 23390, but not by phentolamine. We conclude that NE and E stimulate hypothalamic IR-rCRH secretion via alpha 1 and alpha 2 receptors. The effect of NE upon IR-rCRH secretion is not apparently mediated by serotonergic or cholinergic interneurons, but is modulated by the inhibitory neurotransmitter, GABA. These data support the idea that the central catecholaminergic systems are excitatory rather than inhibitory upon CRH secretion when acting directly at the hypothalamic level. PMID- 2901434 TI - Inference of a molecular defect of apolipoprotein B in hypobetalipoproteinemia by linkage analysis in a large kindred. AB - Heterozygous hypobetalipoproteinemia is characterized by reduced plasma concentrations of LDL cholesterol, total triglycerides, and apo B to less than 50% of normal values. The molecular basis of this disorder remains unknown. The phenotype cosegregates with a DNA haplotype of the apo B gene in an Idaho pedigree, with a maximum decimal logarithm of the ratio (LOD) score of 7.56 at a recombination rate of zero. Individuals carrying this haplotype had total cholesterol levels of 96 mg/dl, LDL cholesterol levels of 37 mg/dl, triglycerides levels of 51 mg/dl, and apo B levels of 38 mg/dl. This study strongly suggests that apo B mutations underlie hypobetalipoproteinemia, and demonstrates the power of the candidate gene approach in linkage analysis for unraveling genetic determinants in metabolic disorders of undefined etiology. PMID- 2901435 TI - Cardioselectivity of cetamolol compared with atenolol and nadolol. AB - The selectivity of the beta-adrenoceptor blockade produced by single oral doses of cetamolol, atenolol, and nadolol was compared in normal male subjects. Study 1 established the dose at which each drug provides equivalent beta-1 blockade. Beta 1 blockade was estimated using the degree of inhibition of the increased heart rate (HR) response to graded exercise. Cetamolol (30 mg), atenolol (100 mg), and nadolol (80 mg) all attenuated the HR response to a comparable extent. This result established that the dose ratio of cetamolol:atenolol:nadolol of 1.00:3.33:2.67 provides equipotent beta-1 blockade. This ratio of doses was used in Studies 2 and 3 to evaluate the antagonism of beta-2-mediated responses to titrated doses of intravenous isoproterenol (ISO) by low and high doses of each drug. Beta-2 blockade was assessed using the attenuation of ISO-induced reductions in diastolic blood pressure (DBP) in Study 2 and ISO-induced increases in specific airway conductance (sGAW) in Study 3. For within drug comparisons, antagonism of the HR increase induced by ISO (a response mediated by both beta-1 and beta-2 receptors) was also examined. Treatments included cetamolol (15 and 60 mg), atenolol (50 and 200 mg), and nadolol (40 and 160 mg in Study 2; 40 mg only in Study 3). All drugs tested suppressed the HR, DBP, and sGAW responses to ISO, and this blockade was dose dependent. Cetamolol and nadolol produced approximately equipotent beta-1 blockade, whereas cetamolol at both doses produced a less potent beta-2 blockade. Atenolol antagonized ISO effects on all parameters less than either cetamolol or nadolol. Quantitative cardioselectivity indices revealed that cetamolol 60 mg was the most cardioselective and nadolol 40 mg the least. Data from the three studies demonstrate that cetamolol is cardioselective relative to nadolol and that, in contrast to atenolol, cardioselectivity appears to increase at the higher dose. PMID- 2901436 TI - Geriatric medicine in the United States: new roles for physician assistants. AB - The problem of adequate medical care for the nation's elderly is mounting as this population grows in numbers. While the overall U.S. population has tripled since 1900, the segment over 65 has increased eightfold. Because of the high incidence of chronic illness in persons over 65, they consume a disproportionate amount of health care. Contributing to the problem are pervasive attitudes of ageism in the U.S. culture (including those of physicians), with the result that old people in the U.S. receive fragmented and often substandard medical care, particularly in nursing homes. Although some stirrings of activity in geriatric medicine are apparent in medical schools, not nearly enough faculty are available to teach courses and the interest of medical students is low. Several trends indicate that physician assistants are prepared to help fill the gaps in health care of the elderly. First, as physician extenders, these allied health professionals have demonstrated that they can perform approximately 80% of primary care tasks carried out by physicians at no sacrifice of quality. Second, a large proportion of the current caseload of physician assistants is patients over the age of 65. Third, physician assistant training programs have incorporated a fivefold increase in geriatric courses into their curricula since 1980, and both students and graduates show a high interest in this field. Finally, reimbursement policies of third party payers indicate a trend toward underwriting more physician assistant services. For example, Medicare Part B recently included payment of physician assistants in nursing homes and hospitals. PMID- 2901437 TI - Neuropeptide- and neurotransmitter-related immunoreactivities in the developing rat olfactory bulb. AB - The development of neuropeptide and neurotransmitter-related immunoreactivities in the rat olfactory bulb were investigated immunohistochemically by using antisera raised against substance P (SP), cholecystokinin-8 (CCK), neurotensin (NT), leucine-enkephalin or methionine-enkephalin-Arg6-Gly7-Leu8 (ENK), somatostatin (SOM), neuropeptide Y (NPY) and tyrosine hydroxylase (TH). Results obtained for the adult olfactory bulb confirmed previous observations, except for SP-like immunoreactive (SP-IR) granule cells in the main olfactory bulb (MOB) and NT-IR neurons around the modified glomerular complex (MGC) (Teicher et al., Brain Res. 194:530-535, 1980). SP-, CCK- and NT-IR neurons were observed in the MOB of the rat fetus. SP-IR neurons also appeared in the accessory olfactory bulb (AOB). Among them, NT-IR neurons in the MOB and SP-IR neurons in the AOB were observed on embryonic day 16. SP- and CCK-IR neurons in the MOB appeared on embryonic day 18. Most of these neurons were presumed to be projecting neurons. SOM-, NPY-, ENK and TH-IR neurons appeared in the newborn rats. The number and intensity of immunostaining of these neurons continued to increase with age, producing the adult pattern, except for NT-IR neurons in the MGC and SP-IR neurons in the mitral cell layer of the AOB, which were more numerous and intensely stained in young animals. PMID- 2901438 TI - Neurochemical organization of the hypothalamic projection to the spinal cord in the rat. AB - The hypothalamus provides a major projection to the spinal cord that innervates primarily lamina I of the dorsal horn and the sympathetic and parasympathetic preganglionic cell columns. We have examined the chemical organization of the neurons that contribute to this pathway by using combined retrograde transport of fluorescent dyes and immunohistochemistry for 15 different putative neurotransmitters or their synthetic enzymes. Our results demonstrate that 5 cytoarchitectonically distinct cell groups in the hypothalamus contribute to the spinal projection and that each has its own predominant chemical types. In the paraventricular nucleus, substantial numbers of hypothalamo-spinal neurons stain with antisera against arginine vasopressin (25-35%), oxytocin (20-25%), and met enkephalin (10%). About 25% of the neurons with spinal projections in the retrochiasmatic area stain with an antiserum against alpha-melanocyte-stimulating hormone. Nearly 100% of the hypothalamo-spinal neurons in the tuberal lateral hypothalamic area stain with this same antiserum, but these cells do not stain for other proopiomelanocortin-derived peptides, and so probably contain a cross reacting peptide. This population must be distinguished from an adjacent cell group, in the perifornical region, where many spinal projection neurons stain with antisera against dynorphin (25%) or atrial natriuretic peptide (20%). Finally, in the dorsal hypothalamic area as many as 55-75% of the neurons with spinal projections are dopaminergic, on the basis of their staining with an antiserum against tyrosine hydroxylase. These 5 neurochemically distinct projections from the hypothalamus to the spinal cord are discussed in the context of their possible functional significance. PMID- 2901439 TI - Catecholaminergic neurons in the ventrolateral medulla and nucleus of the solitary tract in the human. AB - Catecholaminergic neurons in the ventrolateral medulla (VLM) and nucleus of the solitary tract (NTS) are important because of their presumed roles in autonomic regulation, including the tonic and reflex control of arterial pressure, neuroendocrine functions, and the chemosensitivity associated with the ventral medullary surface. However, little is known about the connections of these neurons in the human brain. As a first step in analyzing the functional biochemical anatomy of catecholamine neurons in the human, we used antisera against tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) to localize medullary catecholamine-containing neurons and processes in the VLM and the NTS. Cells staining for TH were located throughout the VLM. Most cells staining for TH and PNMT, which are therefore adrenergic, occurred in an area of the VLM probably corresponding to the rostroventrolateral reticular nucleus. Axons of TH-immunoreactive neurons in the VLM projected (1) dorsally, in a series of parallel transtegmental trajectories, toward the dorsomedial reticular formation, the NTS, and vagal motor nucleus, (2) longitudinally, through the central tegmental field, as fascicles running parallel to the neuraxis, (3) ventrolaterally toward the ventral surface (VS) of the rostral VLM where they appeared to terminate, and (4) medially into the raphe, where they arborized. Similar systems of fibers were labeled for PNMT; the longitudinal bundles of PNMT-labeled axons were limited to the principal tegmental bundle and concentrated dorsally. Fibers containing PNMT were also identified in the medullary raphe, on the medullary ventral surface, and contacting intraparenchymal blood vessels. In the NTS, neurons exhibited immunoreactivity to both TH and PNMT: Four principal subgroups of TH-immunoreactive neurons were seen: a ventral, an intermediate, a medial, and a dorsal group. Perikarya containing PNMT were restricted to the dorsolateral aspect of the NTS. Processes containing TH and PNMT immunoreactivity were identified in the medial and dorsolateral NTS; others appeared to project between the NTS and the VLM and within the solitary tract. The presence of catecholaminergic fibers of the VLM interconnecting with the NTS, raphe, intraparenchymal microvessels, VS, and possibly the spinal cord suggests that the autonomic and chemoreceptor functions attributed to these neurons also may apply to the human. PMID- 2901440 TI - Diagnostic approach and proposed criteria for the clinical diagnosis of Takayasu's arteriopathy. AB - The criteria proposed for the clinical diagnosis of Takayasu's disease (chronic inflammatory arteriopathy of unknown origin) were based on clinical and angiographic data from 108 Japanese patients: 96 with Takayasu's disease and 12 with another disease of the aorta. The criteria consist of one obligatory criterion (age less than or equal to 40 years), two major criteria (left and right mid subclavian artery lesions) and nine minor criteria (high erythrocyte sedimentation rate, common carotid artery tenderness, hypertension, aortic regurgitation or annuloaortic ectasia and lesions of the pulmonary artery, left mid common carotid artery, distal brachiocephalic trunk, thoracic aorta and abdominal aorta). In addition to the obligatory criterion, the presence of two major criteria or of one major plus two or more minor criteria, or of four or more minor criteria suggests a high probability of the presence of Takayasu's disease. The criteria had an 84% sensitivity in 96 patients with this disease: 52 (96%) of 54 patients in the active young group, 8 (80%) of 10 in the active older group, 14 (67%) of 21 in the inactive young group and 7 (64%) of 11 in the inactive older group fulfilled the criteria; however, none of the 12 patients with other aortic diseases did so. Use of these criteria has shortened the delay of an accurate diagnosis in patients with Takayasu's disease. PMID- 2901441 TI - 5-Hydroxytryptamine and catecholamines in developing sympathetic cells of the rat. AB - Appearance of 5-hydroxytryptamine (5-HT) in developing sympathetic cells of prenatal rats was studied using the indirect immunofluorescence method. In consecutive sections, tyrosine hydroxylase (TH) immunoreactivity was considered as a marker for catecholamine-synthesizing cells in general, while phenylethanolamine N-methyltransferase (PNMT) immunoreactivity was used as an indicator of adrenaline synthesis. 5-HT immunoreactivity was observed for the first time in 12.5-day-old embryos in developing sympathetic chain ganglia. On day 13.5, 5-HT-immunoreactive cells were first seen on the preaortic region and on day 14.5 in the developing adrenal gland. Comparison with consecutive sections stained for TH revealed that all TH-immunoreactive cells were also 5-HT immunoreactive. During later development, however, 5-HT immunoreactivity was retained by some cell types in each sympathetic tissue. In the ganglia, most developing principal nerve cells gradually lost their 5-HT immunoreactivity, while all so-called small intensely fluorescent (SIF) cells remained intensely 5 HT-immunoreactive. In the adrenal medulla, all catecholamine-containing cells showed 5-HT immunoreactivity until day 16.5. The first adrenaline-synthesizing cells appeared at this stage. Occasionally on day 16.5 and constantly on day 17.5 noradrenaline cell islets were distinguished among adrenaline cells. The adrenaline cells retained intense 5-HT immunoreactivity, while the noradrenaline cells were non-reactive to it. In the main retroperitoneal paraganglion, two noradrenaline cell populations were distinguished from day 15.5, one being 5-HT immunoreactive and the other non-reactive. A third population appeared in this tissue at the time of birth, consisting of adrenaline-synthesizing cells which were also 5-HT-immunoreactive. These results indicate that the 3 sympathetic tissues undergo similar developmental changes: 5-HT immunoreactivity occurs in conjunction with the initiation of catecholamine synthesis and appears first in all catecholamine cells. During maturation it is confined to certain subpopulations in each tissue, i.e. the SIF cells and some principal nerve cells of the ganglion, the adrenaline cells of the adrenal medulla, the adrenaline cells and some noradrenaline cells of the paraganglionic tissue. PMID- 2901442 TI - Olsalazine as an alternative therapy in a patient with sulfasalazine-induced eosinophilic pneumonia. AB - A man with Crohn's colitis developed eosinophilic pneumonia after treatment with sulfasalazine. Challenge with sulfapyridine revealed that this component of sulfasalazine was the likely causative agent. Treatment with olsalazine, a 5 aminosalicylic acid compound (disodium-azodisalicylate), was well tolerated without recurrence of pulmonary symptoms. PMID- 2901443 TI - Does sulfasalazine induce alopecia? PMID- 2901444 TI - Evidence for multigene control of cryptorchidism in swine. AB - The mode of inheritance of cryptorchidism was investigated in Duroc swine. Matings of cryptorchid males with females whose full-sib brothers were cryptorchids were done. Sixteen of these litters were farrowed, and 54 males were born, of which 8 were cryptorchid. Two hypotheses were examined: first, that this trait is controlled by homozygosity of a recessive gene at a single locus; second, that it is controlled by homozygosity of recessive genes at two loci. The single-locus recessive hypothesis was rejected (P less than .01), but the two locus model was not. Culling to reduce the incidence of cryptorchidism is discussed. PMID- 2901445 TI - All CD2-positive human lymphocytes rosette with sheep erythrocytes in the presence of polyethylene glycol. AB - The efficiency of rosette formation between human peripheral resting lymphocytes and sheep erythrocytes (E) is remarkably increased in the presence of 1-4% polyethylene glycol of MW 10,000 (PEG). In fact, all CD2 ('sheep E receptor') positive lymphocytes formed rosettes. CD2 positivity was assayed by immunofluorescence staining with the monoclonal antibody (mAb) Leu 5b. PEG also induced autologous E rosetting which otherwise did not take place under the usual conditions. The specificity of the rosettes was assessed by blocking CD2 with mAb Leu 5b and by blocking the CD2 target structure (T11TS) on the sheep E with the mAb L180/1. The mAb Leu 5b abolished all rosette formation, but mAb L180/1 only abolished the sheep E rosettes as this mAb is specific for sheep E and does not cross-react with human E. The results indicate that sheep E in the presence of PEG specifically rosette with all CD2-positive lymphocytes. PMID- 2901446 TI - Evaluation of enzyme-linked immunosorbent assay (ELISA), indirect hemagglutination (IHA), counterimmunoelectrophoresis (CIEP), and immunodiffusion (ID) in the serodiagnosis of amebiasis. PMID- 2901447 TI - Advances in cancer pain management: a review of patient-controlled analgesia. PMID- 2901448 TI - Molecular aspect on regulation of HTLV-1 replication and leukemogenesis. PMID- 2901449 TI - Bacterial adherence in urinary tract infections. PMID- 2901450 TI - HTLV-1 infection due to mother milk and blood transfusion. PMID- 2901451 TI - HTLV-1 associated myelopathy (HAM). PMID- 2901452 TI - Comments on adult T cell leukemia. PMID- 2901453 TI - Strongyloides infection and bacterial meningitis in immunocompromised host, especially anti-HTLV-1 antibody positive patients. PMID- 2901454 TI - Testicular cancer in young men: the search for causes of the epidemic increase in the United States. AB - A case-control study of 271 men with testicular cancer and 259 controls was conducted in the Washington, DC area to evaluate whether suggested risk factors could be responsible for the epidemic increases in testicular cancer in young men. No substantial risks were associated with a history of groin hernia operation, the common childhood diseases, allergies, x rays below the waist, venereal disease, vasectomy, or external means of elevating the temperature of the testis. Excess risks were associated with a history of undescended testis (RR = 3.7, CI = 1.5-9.5), testicular trauma (RR = 2.6, CI = 1.6-4.2), and mumps orchitis (RR = 5.8, CI = 0.7-129.7). It is unlikely, however, that any of these conditions has increased sufficiently over time to markedly affect the testicular cancer incidence patterns. Therefore, while the risk factors identified in this paper are of epidemiological interest, they do not account for the increase in testicular cancer in young men. PMID- 2901455 TI - The value of England and Wales congenital malformation notification scheme data for epidemiology: male genital tract malformations. AB - Data from the England and Wales national congenital malformation notification scheme were examined for associations of male genital tract malformations. For some of the malformations comparison of notification rates with the literature suggested gross undernotification. There was also evidence suggesting bias: examination of the relationships of the malformations to birth weight, maternal parity, and maternal age at delivery showed some highly significant trends in risk, most of which were at variance with findings in the literature, and several potential mechanisms for bias could be adduced. Direct investigation is needed, for this and other similar data sets, of the extent and mechanisms of biased undernotification. PMID- 2901456 TI - Release of neuroactive substances: homocysteic acid as an endogenous agonist of the NMDA receptor. AB - Sulfur containing amino acids such as homocysteic acid (HCA), cysteinsulfinic acid, homocysteinsulfinic acid are released by depolarization of slices from various rat brain regions in a Ca++-dependent manner. L-HCA excites caudate neurons through their N-methyl-D-aspartic acid (NMDA) receptor and potentiates their cortically evoked excitatory postsynaptic potentials. 35S-methionine can label the releasable pool of HCA, and thus appears as a precursor of HCA. Thus HCA is a transmitter candidate which acts predominantly on the NMDA receptor. PMID- 2901457 TI - Anticonvulsant drug action and regional neurotransmitter amino acid changes. AB - The role played by the inhibitory transmitters, GABA, glycine and taurine, and by excitatory (aspartate/glutamate) antagonists in mediating anticonvulsant action will be documented. This study provides examples of one anticonvulsant compound that affects glycine metabolism (milacemide), and another that affects aspartate metabolism (beta-methylene-aspartate). Beta-Methylene-aspartate, a selective inhibitor of glutamate-aspartate transaminase activity, protects against sound induced seizures in audiogenic DBA/2 mice, with an ED50 value of 1.9 mumoles (icv; clonic phase). Forebrain and cerebellar aspartate, glutamate and GABA levels are reduced by 15-30% following the administration of beta-methylene aspartate. Milacemide, a glycinamide derivative with experimental and clinical anticonvulsant activity, is ineffective against sound-induced seizures in DBA/2 mice. Following the ip administration of milacemide (100 mg/kg; 3 hours) there were significant increases in rat brain glycine levels in the cerebellum (+137%), cortex (+45%) and hippocampus (+59%). PMID- 2901458 TI - A two-dimensional electrophoresis study of phosphorylation and dephosphorylation of chromaffin cell proteins in response to a secretory stimulus. AB - Phosphorylated proteins of bovine chromaffin cells, radioactively labeled with [32P]orthophosphate, have been analyzed by two-dimensional polyacrylamide gel electrophoresis and autoradiography. Complex two-dimensional electrophoretograms were studied with the aid of computer-assisted image analysis (CAIA). A database map of 32P-labeled proteins was constructed; approximately 500 polypeptides have been detected, numbered, and characterized according to the intensity of labeling, molecular weight, and isoelectric point. The database was constructed from cells kept in resting conditions or stimulated with 59 mM K+ in 2.5 mM Ca2+ or in 0 Ca2+ solution. These manipulations caused statistically significant changes in the degree of phosphorylation of 20 proteins; they were classified as Ca2+-dependent substrates for the phosphorylation or dephosphorylation processes. These changes were also shown in cells stimulated in the presence of the Ca2+ channel activator Bay K 8644. New proteins that show as much as a fivefold increase in their phosphorylation state during cell stimulation have been located with this methodology, as well as many others that had not previously been detected with conventional methods. These experiments provide the first CAIA database of chromaffin cell phosphoproteins; the map constructed with these data will allow the location of specific phosphoproteins and serve as a reference for future ongoing studies. The database will continue to grow to identify more proteins and to facilitate the comparison of complex patterns obtained in different laboratories for normal and transformed pheochromocytoma PC12 cells. PMID- 2901459 TI - Phorbol esters attenuate glutamate-stimulated inositol phospholipid hydrolysis in neuronal cultures. AB - The phorbol diesters 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and phorbol 12,13-dibutyrate, but not 4-alpha-phorbol-didecanoate, inhibited the stimulation of inositol phospholipid hydrolysis by excitatory amino acids and carbamylcholine in primary cultures of cerebellar neurons. This inhibition was mimicked by the synthetic diacylglycerol 1,2-dioleoyl-rac-glycerol (DOG) and was selective for a specific glutamate-phosphoinositide receptor subtype (GP2 receptor) activated by glutamate and quisqualate. TPA was nearly inactive in inhibiting the stimulation of inositol phospholipid hydrolysis by N-methyl-D-aspartate, a selective agonist of the GP1 receptor. Phorbol diesters and DOG attenuated the stimulation of inositol phospholipid hydrolysis by glutamate and quisqualate also in cerebellar slices from 9-15-day-old rats; however, using this preparation, their action was weak and required high concentrations (greater than 1 microM). The inhibition of signal transduction by phorbol diesters was not consequent to a reduced binding of glutamate to its membrane recognition sites. In fact, TPA induced only a small increase in the KD but no change in the Bmax of [3H]glutamate binding in cerebellar membranes. Phorbol diesters may act to inhibit specific GTP-binding proteins or particular molecular forms of phosphoinositidase C associated with GP2 or muscarinic cholinergic receptors. PMID- 2901460 TI - ATP-dependent glutamate uptake into synaptic vesicles from cerebellar mutant mice. AB - The ATP-dependent glutamate uptake system in synaptic vesicles prepared from mouse cerebellum was characterized, and the levels of glutamate uptake were investigated in the cerebellar mutant mice, staggerer and weaver, whose main defect is the loss of cerebellar granule cells, and the nervous mutant, whose main defect is the loss of Purkinje cells. The ATP-dependent glutamate uptake is stimulated by low concentrations of chloride, is insensitive to aspartate, and is inhibited by agents known to dissipate the electrochemical proton gradient. These properties are similar to those of the glutamate uptake system observed in the highly purified synaptic vesicles prepared from bovine cortex. The ATP-dependent glutamate uptake system is reduced by 68% in the staggerer and 57-67% in the weaver mutant; these reductions parallel the substantial loss of granule cells in those mutants. In contrast, the cerebellar levels of glutamate uptake are not altered significantly in the nervous mutant, which has lost Purkinje cells, but not granule cells. In view of evidence that granule cells are glutamatergic neurons and Purkinje cells are GABAergic neurons, these observations support the notion that the ATP-dependent glutamate uptake system is present in synaptic vesicles of glutamatergic neurons. PMID- 2901461 TI - Source and physiological significance of plasma 3,4-dihydroxyphenylalanine in the rat. AB - To elucidate the source and physiological significance of plasma 3,4 dihydroxyphenylalanine, the immediate product of the rate-limiting step in catecholamine biosynthesis, plasma 3,4-dihydroxyphenylalanine was quantified in conscious rats after administration of reserpine, desipramine, clorgyline, or forskolin, treatments that affect tyrosine hydroxylase activity. Plasma 3,4 dihydroxyphenylalanine was also examined during infusions of norepinephrine with or without clorgyline, reserpine, or desipramine pretreatment. After reserpine, the plasma 3,4-dihydroxyphenylalanine level decreased by 22% and then increased by 40%, a result consistent with modulation of tyrosine hydroxylase activity first by an increased axoplasmic norepinephrine content and then by depletion of norepinephrine stores. After desipramine, the plasma 3,4-dihydroxyphenylalanine level decreased by 20%, reflecting the depressant effect of neuronal uptake blockade on norepinephrine turnover. Forskolin increased the plasma 3,4 dihydroxyphenylalanine level by 30%, consistent with activation of tyrosine hydroxylase by cyclic AMP-dependent phosphorylation. Acute administration of clorgyline was without effect on the plasma 3,4-dihydroxyphenylalanine level. Norepinephrine infusions decreased the plasma 3,4-dihydroxyphenylalanine concentration, as expected from end-product inhibition of tyrosine hydroxylase. Pretreatment with desipramine prevented the norepinephrine-induced decrease in plasma dihydroxyphenylalanine content, indicating that inhibition of tyrosine hydroxylase required neuronal uptake of norepinephrine. Both reserpine and clorgyline augmented the norepinephrine-induced decrease in plasma 3,4 dihydroxyphenylalanine level, suggesting that retention of norepinephrine in the axoplasm--due to inhibition of norepinephrine sequestration into storage vesicles or catabolism--caused further inhibition of tyrosine hydroxylase. Changes in plasma 3,4-dihydroxyphenylalanine concentration during norepinephrine infusions were negatively correlated with those in plasma 3,4-dihydroxyphenylglycol level, a finding consistent with modulation of tyrosine hydroxylase activity by axoplasmic norepinephrine. In reserpinized animals, clorgyline and norepinephrine infusion together decreased the plasma 3,4-dihydroxyphenylalanine content by 50%, a result demonstrating that hydroxylation of tyrosine was depressed by at least half. The results indicate that quantification of plasma 3,4 dihydroxyphenylalanine can provide a simple and direct approach for examination of the rate-limiting step in catecholamine biosynthesis. PMID- 2901462 TI - Butyrylcholinesterase in human brain and acetylcholinesterase in human plasma: trace enzymes measured by two-site immunoassay. AB - Enzyme-linked immunosorbent assays for acetylcholinesterase (AChE) and for butyrylcholinesterase (BuChE) were markedly more specific than conventional assays using selective enzyme inhibitors. The new assays were used with blood and brain samples containing traces of one enzyme dominated by large amounts of the other. The results showed that human plasma does contain AChE (8 ng/ml), even though its major cholinesterase is BuChE (3,300 ng/ml). BuChE immunoreactivity was not detected in human red blood cells but occurred in all brain regions. The cerebellum was the richest region tested (540 ng of BuChE/g of tissue), whereas the cerebral cortex was the poorest (240 ng of BuChE/g). However, because of the small local AChE content (99 ng/g), BuChE was the major cortical cholinesterase. The picture was reversed in the putamen, where BuChE immunoreactivity (340 ng/g) was far outweighed by that of AChE (6,100 ng/g). PMID- 2901463 TI - Inactivation of tyrosine hydroxylase activity by ascorbate in vitro and in rat PC12 cells. AB - Tyrosine hydroxylase activity is reversibly modulated by the actions of a number of protein kinases and phosphoprotein phosphatases. A previous report from this laboratory showed that low-molecular-weight substances present in striatal extracts lead to an irreversible loss of tyrosine hydroxylase activity under cyclic AMP-dependent phosphorylation conditions. We report here that ascorbate is one agent that inactivates striatal tyrosine hydroxylase activity with an EC50 of 5.9 microM under phosphorylating conditions. Much higher concentrations (100 mM) fail to inactivate the enzyme under nonphosphorylating conditions. Isoascorbate (EC50, 11 microM) and dehydroascorbate (EC50, 970 microM) also inactivated tyrosine hydroxylase under phosphorylating but not under nonphosphorylating conditions. In contrast, ascorbate sulfate was inactive under phosphorylating conditions at concentrations up to 100 mM. Since the reduced compounds generate several reactive species in the presence of oxygen, the possible protecting effects of catalase, peroxidase, and superoxide dismutase were examined. None of these three enzymes, however, afforded any protection against inactivation. We also examined the effects of ascorbate and its congeners on the activity of tyrosine hydroxylase purified to near homogeneity from a rat pheochromocytoma. This purified enzyme was also inactivated by the same agents that inactivated the impure corpus striatal enzyme. Under conditions in which ascorbate almost completely abolished enzyme activity, we found no indication for significant proteolysis of the purified enzyme as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. We also found that pretreatment of PC12 cells in culture for 4 h with 1 mM ascorbate, dehydroascorbate, or isoascorbate (but not ascorbate sulfate) also decreased tyrosine hydroxylase activity 25 50%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901464 TI - Identification and function of octopamine and tyramine conjugates in the Limulus visual system. AB - Major metabolites of octopamine and tyramine in the Limulus nervous system are identified here as gamma-glutamyl octopamine and gamma-glutamyl tyramine. We show that these conjugates are normal products of amine metabolism in Limulus, and that they are normally present in octopamine-rich Limulus tissues. The synthesis of these conjugates is not restricted to nervous tissue, but the highest activity of gamma-glutamyl amine synthetase was measured in the CNS. Our interest in these molecules stems from our previous observations which showed that they were synthesized and stored in, and released from, the efferent fibers to Limulus eyes which modulate the sensitivity of the eyes to light. Here we provide direct evidence for the release of the conjugates from Limulus eyes in response to depolarization, and that gamma-glutamyl octopamine can increase the sensitivity of the lateral eye to light. Our observations lend support to the hypothesis that gamma-glutamyl octopamine may serve as an intercellular messenger in the Limulus visual system. PMID- 2901466 TI - Madreporic coral: a new bone graft substitute for cranial surgery. AB - Since 1985, the authors have been using madreporic coral fragments (genera Porites) as a bone graft substitute. Of the 167 coral grafts implanted, 150 were coral "corks" used to obliterate burr holes (diameter 10 mm), five were large implants (length 20 to 40 mm) to repair skull defects, and 12 were coral blocks to reconstruct the floor of the anterior cranial fossa. Previous experimental studies suggested that coral grafts would be well tolerated and become partially reossified as the calcific skeleton was resorbed. The authors describe their experience and detail the main biological properties of these materials, which appear to be very promising for use in cranial reconstructive surgery. PMID- 2901465 TI - Importance of glutamine for gamma-aminobutyric acid synthesis in rat neostriatum in vivo. AB - This work was carried out to evaluate the importance of glial cells in providing precursors for the in vivo synthesis of gamma-aminobutyric acid (GABA). Fluorocitrate, which selectively inhibits the tricarboxylic acid cycle in glial cells, was administered locally in rat neostriatum. Inhibition of the glial cell tricarboxylic acid cycle led to a decrease both in glutamine level and in gamma vinyl GABA (GVG)-induced GABA accumulation, an observation indicating reduced GABA synthesis. The role of glutamine, which is synthesized in glial cells as a precursor for GABA, was further investigated by inhibition of glutamine synthetase with intrastriatally administered methionine sulfoximine. In this case, the glutamine level was reduced to near zero values, and the GVG-induced GABA accumulation was only half that of normal. The results show that glutamine is an important precursor for GABA synthesis, but it cannot be the sole precursor because it was not possible to depress the GVG-induced GABA accumulation completely. PMID- 2901467 TI - Evaluation of the sorbent suspension reciprocating dialyser in the treatment of overdose of paracetamol and phenobarbitone. AB - Poisoning with paracetamol (acetaminophen) and phenobarbitone is a common occurrence in the United States and Europe. The removal efficiency of these drugs by a sorbent suspension reciprocating dialyser (SSRD) has been investigated. The SSRD is a parallel plate dialyser with a reciprocating blood flow and free mobile sorbent suspension composed of charcoal and zeolites. This arrangement provided a system with minimal sorbent saturation. High performance liquid chromatography was used for the quantification of the drugs in aqueous and serum fluids. The in vitro removal efficiency of the dialyser was studied by dialysing a large volume of the drug in solution for 12 to 16 h. The removal efficiency remained relatively constant up to 10 h of dialysis. The in-vivo dialysis studies were performed using normal dogs. Large doses of the drugs were administered orally or intravenously to achieve high blood levels. The clearance values obtained from these studies were comparable with, or in excess of, the values reported in the literature for conventional dialysers. The major advantage of the SSRD is the ability of the unit to be used for prolonged dialysis and to provide a system with minimal sorbent saturation due to mixing and interchange of sorbent granules next to the membrane surface. PMID- 2901468 TI - Theophylline metabolism by human, rabbit and rat liver microsomes and by purified forms of cytochrome P450. AB - The capacity of human, rabbit and rat liver microsomes and purified isozymes of cytochrome P450 to metabolize theophylline has been assessed. In all three species the 8-hydroxylation of theophylline to 1,3-dimethyluric acid (1,3-DMU) was the major pathway. In human, control rabbit and rat liver microsomes this metabolite accounted for 59, 77 and 94%, respectively, of the total metabolites formed. In both human and control rabbit liver microsomes the N-demethylation of theophylline to 1-methylxanthine (1-MX) accounted for 20% of the total metabolites formed. N-demethylation of theophylline to 3-methylxanthine (3-MX) accounted for 21% of theophylline metabolism in human microsomes but was a minor pathway in control rabbit and rat microsomes. Acetone and phenobarbitone pretreatment markedly increased the formation of 1,3-DMU by rabbit liver microsomes. Rifampicin and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administration caused a slight but significant increase in this pathway. In general the N-demethylation pathways in rabbit liver microsomes were refractory to induction. In the rat, the metabolism of theophylline to 1-MX, 3-MX and 1,3 DMU were all significantly increased in Aroclor 1254, dexamethasone, phenobarbitone and 3-methylcholanthrene-treated microsomes. In reconstitution experiments the polycyclic hydrocarbon inducible rabbit cytochrome P450 Forms 4 and 6 and the constitutive Form 3b all metabolized theophylline to its three metabolites. In human liver microsomes from four subjects anti-rabbit cytochrome P450 Form 4 IgG inhibited the metabolism of theophylline to 1-MX, 3-MX and 1,3 DMU by approximately 30%. These data indicate that theophylline is metabolized by multiple forms of cytochrome P450 in human, rabbit and rat liver microsomes. PMID- 2901469 TI - The effect of varying percentages of haemodilution with fluosol-DA or normal saline on antipyrine metabolism in the rat. AB - Antipyrine disposition and metabolism in conscious, unrestrained rats after 25 or 50% haemodilution with Fluosol or normal (0.9% NaCl) saline is reported. Rats received an intravenous antipyrine dose (20 mg kg-1) 0.5, 24, 48, or 72 h after haemodilution and its pharmacokinetic parameters have been compared with non exchanged control animals. Haemodilution 25% with Fluosol initially depressed antipyrine metabolism for 24 h by decreasing the antipyrine urinary excretion rate constant and the formation rate constants of 4-hydroxyantipyrine (4-OH) and 3-hydroxymethylantipyrine (3-OHME). Metabolism was then increased for 48 and 72 h with a slight increase in all rate constants. Haemodilution 50% with Fluosol produced a similar pattern but with significant increases in the 3-OHME formation rate constant found at 48 and 72 h. Haemodilution 25% with saline reduced 4-OH formation for 48 h. Haemodilution 50% with saline significantly reduced antipyrine urinary excretion at all times. After a significant increase in the 4 OH and 3-OHME formation rate constants at 24 h following 50% haemodilution with saline, the rate constants were significantly decreased at 48 and 72 h. Haemodilution 25% with Flusol significantly reduced the antipyrine Vd at 0.5 and 72 h. After haemodilution 50% with Fluosol, the Vd alternated between values greater and less than control throughout the 72 h. Haemodilution 25 or 50% with saline had little influence on Vd. PMID- 2901470 TI - The oral disposition of zinc following the use of an anticalculus toothpaste containing 0.5% zinc citrate. AB - Zinc is retained in the mouth after use of a toothpaste containing 0.5% zinc citrate. More than one third of the dose was found to be retained after normal brushing. Elevated zinc levels were also found in plaque. Saliva zinc levels were significantly above background for at least 2 h after brushing. In-vitro experiments demonstrated that zinc can bind to the pellicle-coated tooth surface and can subsequently adsorb into saliva. Plaque can calcify to form calculus containing appreciable levels of hydroxyapatite. Zinc adsorbs to hydroxyapatite inhibiting crystal growth. Levels of zinc in plaque were found to be considerably higher than those taken up by hydroxyapatite in an in-vitro test of crystal growth inhibition indicating the potential of zinc to inhibit calculus formation. PMID- 2901471 TI - Sex-related differences in disposition and response to phenprocoumon in rats. AB - The pharmacokinetics and the pharmacological response to phenprocoumon have been studied in female and male inbred Lewis-Wistar rats. A significantly lower clearance was found in female than in male rats (7.9 +/- 1.4 vs 24.5 +/- 2.5 mL h 1 kg-1, respectively; t = 15.09, P less than 0.001) as well as a lower apparent volume of distribution (288 +/- 46 vs 617 +/- 105 mL kg-1; t = 7.58, P less than 0.001) and a longer half-life (25.5 +/- 3.4 vs 17.5 +/- 1.8 h; t = 5.16, P less than 0.001). The binding of phenprocoumon was higher in female than in male rats (fu: 0.0096 +/ 0.0008 vs 0.0124 +/- 0.0007, respectively; t = 6.66, P less than 0.001). The total (C) as well as the unbound concentration (Cu) needed to elicit a 50% decrease in the prothrombin complex synthesis rate was substantially higher in female rats: C50 was 377 +/- 98 ng mL-1 in female and 155 +/- 29 ng mL-1 in male rats (t = 5.32, P less than 0.001), whereas Cu50 was 3.6 +/- 0.7 ng mL-1 in female and 1.9 +/- 0.3 ng mL-1 in male rats (t = 5.50, P less than 0.001). However, because of the lower clearance and volume of distribution and the longer half-life in female rats, the female rats experienced a higher cumulative effect than male rats to 0.34 mg kg-1 i.v. doses. PMID- 2901472 TI - Cardiovascular and renal actions of calcium channel blocker chemical subgroups: a search for renal specificity. AB - The diuretic and natriuretic responses to structurally distinct classes of Ca2+ channel blockers have been compared, to determine whether any agent provoked K+ sparing natriuresis, and to assess the relation of such responses with drug effects on blood pressure. Conscious normotensive Sprague-Dawley rats received vehicle or one of the following drugs in an oral saline load (40 mL kg-1) nifedipine, nimodipine, nitrendipine, prenylamine, cinnarizine, flunarizine, diltiazem, verapamil, hydrochlorothiazide, amiloride, or hydralazine, at doses from 0.316 to 100 mg kg-1. Urine was collected for 6h. Blood pressure was monitored directly in parallel studies. Diltiazem (31.6, 100 mg kg-1) and flunarizine (100 mg.kg-1) enhanced urine and electrolyte excretion in spite of marked hypotension; diltiazem was the only drug to produce dose-related renal responses. In contrast, equihypotensive doses of hydralazine and nifedipine produced overt urine and electrolyte retention. Nitrendipine and prenylamine (0.316 mg kg-1 each) produced slight diuresis or natriuresis without altering blood pressure; higher doses had no effect. The 31.6 mg kg-1 doses of verapamil, nitrendipine, and nimodipine markedly reduced blood pressure, but neither enhanced nor limited urine and electrolyte excretion. Cinnarizine failed to produce any cardiovascular or renal effects. Diuretic responses evoked by the Ca2+ channel blockers were not class-specific, showed no tendency towards sparing K+, were generally weaker than those produced by low doses of amiloride or hydrochlorothiazide, and were dissociable from drug-induced changes in blood pressure. PMID- 2901473 TI - Comparison of the in-vitro receptor selectivity of substituted benzamide drugs for brain neurotransmitter receptors. AB - The in-vitro selectivity of a group of substituted benzamide drugs for brain neurotransmitter receptors was determined to assess the most appropriate drugs for use in human PET studies. All substituted benzamide drugs studied inhibited [3H]haloperidol and [3H]spiperone binding to rat striatal membranes. The most potent compounds were YM 09151-2, clebopride and raclopride. However, these substances also interacted in differing degrees with alpha-1, alpha-2, beta adrenergic, 5-HT-1, 5-HT-2, and opiate sites. Sulpiride, alizapride, SL 74205, TER 1546 and tiapride were specific for D-2 receptors, but these drugs were active only in the 10(-7)-10(-6) M range. Raclopride, amisulpiride and sultopride showed a 100-1000 differentiation between action on dopamine sites compared with other neurotransmitter receptors. No such selectivity was observed for clebopride or YM 09151-2. Specific substituted benzamides such as alizapride, may be appropriate in high concentrations for defining the interaction of PET ligands with brain dopamine receptors. More potent, but selective, drugs such as raclopride and amisulpiride, may be effective in low concentrations as ligands for labelling dopamine receptor sites. However, the ability of these various substituted benzamide drugs to penetrate into brain and in-vivo to identify dopamine receptors in all brain areas must be assessed. PMID- 2901474 TI - A three dimensional receptor model of the dopamine D2 receptor from computer graphic analyses of D2 agonists. AB - Four potent D2 agonists were employed to define a primary pharmacophore for the D2 receptor. Hypothetical receptor points, representing interaction points on a receptor were built on to each molecule. These points and the nitrogen atom were averaged to give the coordinates (A) of the primary pharmacophore: R1 (0.00, 3.50, 0.00), R2 (0.00, -3.50, 0.00), R3 (5.79, 2.06, 0.00), and nitrogen (5.13, 0.63, 0.37). Eight structural classes of D2 agonists were then superimposed on to the primary pharmacophore to aid in the location of secondary binding sites. The secondary sites include two lipophilic clefts, an area of steric bulk, a region to hydrogen bond 'meta' hydroxy groups and a 'critical region' accepting methoxy and halogen substituents but not hydroxy substituents. The model has the potential to design and predict activity of novel D2 agonist compounds. PMID- 2901475 TI - High speed photographic analysis of aerosols produced by metered dose inhalers. AB - The design of pressurized metered dose inhalers (MDI) used to assess asthma is variable. We have examined the aerosol spray flumes generated by four commercially available MDI products using high speed video photography. For this purpose a moulded jacket was designed which could hold the inhaler in an immovable position during actuation. Fresh inhalers were fitted in the jacket after thorough shaking and three successive actuations 30 s apart were filmed with a high speed video camera (200 frames s-1). The aerosol, ejected at high velocity into calm room air, was seen to have a 'jet' phase followed by a 'cloud' phase as a result of particle dispersion. Filming was continued till the flume could no longer be visualized on the TV monitor. High speed photography was used to record flumes seen on the video monitor, to enable characterization of flume appearance, dimensions and mean velocity. PMID- 2901476 TI - Time-dependent distribution and excretion of radiolabelled, semipermeable, stable magnetic microcapsules. AB - The time-dependent excretion and potential body retention of magnetic polyethyleneimine (PEI) microcapsules, methylated with [14C]methyl iodide have been investigated after intragastric administration to mice. Gastric emptying was rapid but about 10% of the administered dose was still present in the stomach after 6 h; the number of microcapsules within the small intestine remained approximately constant over 1-6 h. Excretion of microcapsules in the faeces was virtually complete (98.7% excretion within 72 h), with small amounts of radioactivity excreted via the urine or as [14C]CO2. There was no detectable adsorption or retention of microcapsules within the body as measured by either a whole-body autographic study or by direct quantitation of tissue radioactivity. PMID- 2901477 TI - Prodrug behaviour of nicotinoylmorphine esters. AB - Morphine and its nicotinoyl esters, dinicotinoylmorphine (nicomorphine), 6 mononicotinoylmorphine (6-MNM) and 3-mononicotinoylmorphine (3-MNM) were tested in mice for central activity to obtain time-effect profiles of these compounds in rats. Two effects, analgesia with the hot plate test and locomotor stimulation in activity cages were measured and nicomorphine, 6-MNM and 3-MNM were found to have a faster onset of action compared with morphine. The effects of 3-MNM and morphine lasted longer than the effect of nicomorphine and 6-MNM. The prodrug behaviour of 3-MNM and nicomorphine for morphine and 6-MNM, respectively, is discussed. PMID- 2901478 TI - Excitatory P1-purinoceptors on pre- and post-ganglionic cholinergic nerve terminals in the chick oesophagus. AB - The mechanism of action of ATP and the purinoceptors involved have been investigated on the chick oesophagus. The susceptibility of the excitatory responses to ATP/adenosine to tetrodotoxin indicates that their action is neurally mediated. Blockade of ATP/adenosine responses by atropine suggests the involvement of endogenous acetylcholine. ATP action depends on breakdown to AMP/adenosine, since theophylline blocks ATP/adenosine responses. The inhibition of ATP responses by pentolinium implies the involvement of preganglionic fibres. PMID- 2901479 TI - Enhancement of capsaicin-induced contraction of guinea-pig tracheal smooth muscle by vanadate. AB - Contractions of guinea-pig isolated tracheal smooth muscle by submaximal capsaicin (0.1 microM) were enhanced by 43% (P less than 0.01) after vanadate (10 microM for 10 min) preincubation. Contractile responses to acetylcholine (0.1-100 microM), histamine (1-100 microM) or substance P (0.01-1 microM) were, in contrast, not affected by prior vanadate exposure. It is suggested that tachykinin release from capsaicin-sensitive afferent nerve endings within the airways was enhanced by vanadate while airway smooth muscle reactivity remained unchanged. PMID- 2901480 TI - Propranolol uptake with high capacity by rat perfused lung. AB - Lung isolated from 7-week-old rats was perfused with pH 7.4 Krebs-Ringer bicarbonate buffer solution (35 mL) containing 1 to 100 micrograms mL-1 of propranolol and 3% BSA at the recirculation rate of 8 mL min-1. Almost parallel bi-exponential drug concentration-time curves were obtained at the initial load lower than 10 micrograms mL-1, whereas relatively slow, mono-exponential decline was found after perfusion at 100 micrograms mL-1. Pharmacokinetic analysis for the perfusate propranolol concentration-time curves when loaded at 1 to 10 micrograms mL-1 yielded almost comparable values for the pulmonary perfusion clearance (0.387 +/- 0.092 to 0.486 +/- 0.095 mL min-1 g-1). In contrast, this parameter was significantly reduced at 100 micrograms mL-1 (0.113 +/- 0.042 mL min-1 g-1). The present findings suggest a trend towards saturation kinetics in the in-vitro pulmonary clearance of propranolol. PMID- 2901481 TI - The role of adrenoceptors in the mechanism of reserpine-induced stimulation of gastric acid secretion in the rat. AB - The role of alpha- and beta-adrenoceptors in the mechanism of reserpine-induced stimulation of gastric acid secretion in the rat has been examined. After 6 h reserpine (0.1 mg kg-1 i.p.) significantly stimulated acid secretion relative to control values (176 +/- 4 vs 60 +/- 3 mumol, mean +/- s.e.m., n = 10, P less than 0.001). Neither coeliac ganglionectomy nor propranolol (5-15 mg kg-1) influenced this action. Vagotomy prevented acid stimulation by reserpine and was associated with H+ output similar to that of vagotomy controls (13 +/- 1 vs 14 +/- 1 mumol, mean +/- s.e.m., n = 10). Dose-dependent inhibition of the reserpine-induced acid secretion was produced by phenoxybenzamine or phentolamine; an inhibition similar to that achieved by vagotomy was noted with the 15 mg kg-1 dose (13 +/- 1 and 15 +/- 1 mumol, respectively, vs 176 +/- 4 mumol, mean +/- s.e.m., n = 10, P less than 0.001). The similarity in action between vagotomy and large doses of phenoxybenzamine or phentolamine suggests that, in the rat, vagal alpha adrenoceptor stimulation is directly involved in the mechanism of reserpine induced stimulation of gastric acid secretion. PMID- 2901482 TI - Chronic antidepressant treatment increases the apomorphine-induced elevation of plasma corticosterone in rats. AB - Plasma corticosterone concentrations in response to subcutaneous administration of apomorphine (25 and 200 micrograms kg-1) have been assessed in rats treated acutely (2 days) or repeatedly (15 days) with saline, clomipramine, electroshock and clomipramine + electroshock. Chronic, but not acute, antidepressant treatment decreased the corticosterone level which remained unchanged in control and in rats acutely treated with apomorphine. Chronic antidepressant treatment significantly increased the corticosterone response to apomorphine. Neuroendocrine evidence is provided for an increased responsiveness of dopamine receptors which are thought to mediate the apomorphine effect on corticosterone secretion following chronic antidepressant treatment. PMID- 2901483 TI - Pharmacological mechanisms of action of flupirtine: a novel, centrally acting, nonopioid analgesic evaluated by its discriminative effects in the rat. AB - Rats were trained to discriminate the novel analgesic flupirtine (10.0 mg/kg i.p., 10 min) from no drug under a two-choice fixed-ratio 5 shock-termination schedule. Flupirtine yielded a dose-response curve with an ED50 of 3.87 mg/kg. The opioid analgesics pentazocine, codeine and tramadol failed to produce flupirtine appropriate responding. The opioid antagonist naltrexone did not antagonize the discriminative effects of flupirtine. The mixed alpha-1/alpha-2 adrenergic agonist clonidine and the highly specific alpha-2 adrenergic agonist UK-14304, both partially and dose-dependently produced flupirtine appropriate responding. The mixed alpha-1/alpha-2 antagonist yohimbine and the highly specific alpha-2 antagonists idazoxan and L-654,284 all partially and dose dependently antagonized flupirtine appropriate responding. Neither of the alpha-1 agonists phenylephrine or ST 587 produced flupirtine appropriate responding, nor did the alpha-1 antagonist prazosin antagonize flupirtine responding. It is concluded that the discriminative effects of flupirtine are neither of opioid nor of alpha-1 adrenergic type, but are primarily mediated through alpha-2 adrenergic mechanisms. PMID- 2901484 TI - Pharmacological characterization of the hyperglycemia induced by alpha-2 adrenoceptor agonists. AB - The selective alpha-2 adrenoceptor agonist UK 14.304 induced in the mouse a dose dependent hyperglycemic response which was accompanied by a concomitant inhibition of insulin secretion. Similar effects were observed with the preferential alpha-2 receptor agonists clonidine and guanabenz whereas less pronounced effects were found with (-)-epinephrine. No significant effects on blood glucose levels were observed with the alpha-1 adrenoceptor agonist methoxamine. Adrenalectomy or depletion of catecholamine stores by reserpine, alpha-methylparatyrosine or DSP4 failed to modify the hyperglycemic response to UK 14.304. However, streptozotocin diabetic mice did not respond to UK 14.304. The hyperglycemia induced by submaximal doses of UK 14.304 was antagonized by the centrally and peripherally acting alpha-2 adrenoceptor antagonists rauwolscine, yohimbine, idazoxan and phentolamine, by the peripheral antagonist benextramine but not by prazosin (alpha-1 selective) or propranolol (beta adrenergic). Thus, it may be suggested that the alpha agonist-induced hyperglycemia is mediated via postsynaptic alpha-2 adrenoceptors located on pancreatic beta cells and that it is mediated through the inhibition of insulin secretion. PMID- 2901485 TI - Alpha and beta adrenoceptor blocking action of carvedilol in the canine mesenteric artery and vein. AB - We observed the effects of carvedilol, a novel beta adrenoceptor blocker, on electrical responses of smooth muscle cells produced by endogenous and exogenous norepinephrine (NE) in isolated canine mesenteric artery and vein. Carvedilol inhibited the NE-induced depolarization in the artery but not in vein, with potencies equivalent to prazosin, i.e., carvedilol blocked alpha 1 adrenoceptors in arterial smooth muscles. Stimulation of perivascular nerves evoked an excitatory junction potential (e.j.p.) and a slow depolarization in these vascular smooth muscles. Carvedilol inhibited the slow depolarization evoked in the artery but not in the vein, with no marked inhibition of the e.j.p.s. High concentrations (10(-5) M) of carvedilol inhibited the e.j.p., slow depolarization, and also the compound action potentials of sympathetic nerve bundles running along the mesenteric vessels, suggesting that these inhibitions were due to local anesthetic actions. The e.j.p. amplitude was increased by isoprenaline and was decreased by NE. The NE and isoprenaline actions were antagonized by yohimbine and propranolol, respectively. Carvedilol inhibited the isoprenaline-actions but not the NE actions on the e.j.p., suggesting that this drug blocked prejunctional beta adrenoceptors but not the alpha 2 adrenoceptors. These results indicate that carvedilol blocks alpha 1 and beta adrenoceptors but not alpha 2 adrenoceptors in vascular tissues. PMID- 2901486 TI - Neurological dysfunction after intrathecal injection of dynorphin A (1-13) in the rat. I. Injection procedures modify pharmacological responses. AB - In rats, the spinal subarachnoid injection of the kappa opioid agonist Dynorphin A (Dyn A)(1-13) and the delta opioid receptor antagonist ICI 174864 produced dose related flaccid paralysis of hindlimbs and tail that were influenced appreciably by injection procedures. When injected through indwelling intrathecal (i.t.) catheters terminating at L1 to L2, both peptides were significantly more potent producing paralysis 1 day, rather than 10 to 14 days, after i.t. catheterization. Other rats received direct subarachnoid injections of these peptides through 30 gauge needles placed in the L4 to L5 intervertebral space. In naive, uncatheterized and acutely catheterized rats, direct intervertebral injection of these peptides, as well as D-Ala2-Dyn A (1-13) amide (a metabolically stable analog of Dyn A (1-13), produced hindlimb paralysis with potencies comparable to those recorded after injections through acutely implanted catheters. In contrast, chronically catheterized rats showed significantly reduced responsivity to direct intervertebral injections of all three of these peptides. Loss of hindlimb motor function was associated with loss of nociceptive responsiveness. Elevations in tail-flick latencies were only seen with doses of Dyn A (1-13) which produced motor dysfunction, and were not blocked or reversed by high doses of the opioid antagonist naloxone. These results indicate that: 1) indwelling i.t. catheters induce spinal cord alterations which complicate their experimental usefulness, 2) Dyn A (1-13) does not alter responsiveness to thermal nociceptive stimuli through opioid mechanism and 3) Dyn A (1-13) causes parallel disruptions of spinal cord motor and nociceptive function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901487 TI - Neurological dysfunction after intrathecal injection of dynorphin A (1-13) in the rat. II. Nonopioid mechanisms mediate loss of motor, sensory and autonomic function. AB - The kappa opioid agonist dynorphin A (Dyn A) (1-13) produced dose-related neurological deficits after subarachnoid injection in the lumbar spinal cords of rats. Whereas the neurological dysfunctions produced by low doses of Dyn A (1-13) were transient, higher doses caused persistent deficits, characterized by motor and nociceptive impairment in hindlimbs and tail, hindlimb edema, priapism, bladder infarction and atony and urinary incontinence. These deficits appeared to result from nonopioid actions of Dyn A (1-13), as they were: 1) not blocked by the opioid antagonists naloxone or WIN 44,441-3; 2) shared by Dyn A (3-13), which lacks opioid activity; and 3) not produced or altered by the selective kappa opioid agonist U 50,488. Coinjection of a combination of peptidase inhibitors, shown previously to enhance the actions of Dyn A fragments in vitro, significantly increased the paralytic actions of Dyn A (1-13). The peptidase inhibitors did not by themselves cause neurological dysfunction, and they did not alter the paralytic potency of the peptidase-resistant delta opioid antagonist ICI 174864. These findings indicate that Dyn A effects were: 1) limited appreciably by its rapid enzymatic degradation after injection and 2) most likely the result of actions of the intact peptide rather than proteolytic products generated after injection. Neuroanatomical evaluations revealed extensive neuronal and axonal injury in the lumbosacral spinal cords of rats injected with 25 nmol of Dyn A (1-13). Collectively, these results indicate that Dyn A (1-13) acts through nonopioid mechanisms to cause the injury and death of neurons involved in diverse spinal cord functions. PMID- 2901488 TI - Differences in the stimulus properties of 3,4-methylenedioxyamphetamine and 3,4- methylenedioxymethamphetamine in animals trained to discriminate hallucinogens from saline. AB - The stimulus properties of 3,4-methylenedioxyamphetamine (MDA), 3,4 methylenedioxymethamphetamine (MDMA) and several related compounds were compared to those of (+)-lysergic acid diethylamide (LSD) and mescaline (3,4,5 trimethoxyphenylethylamine) in a two-lever, water-reinforced, drug discrimination task. In animals trained to discriminate LSD (0.08 mg/kg) from saline (n = 8), LSD-like responding occurred during substitution (generalization) tests with sufficiently high doses of (+/- )-2,5-dimethoxy-4-methylamphetamine, LSD, mescaline, psilocybin and (-)-MDA; saline appropriate responding occurred after (+)-MDA and both (+)- and (+)- and (-)-MDMA. In animals trained to discriminate mescaline (10 mg/kg; n = 8), (-)-MDA, (+)-MDA, (-)-MDMA and (+)-MDMA as well as (+/- )-2,5-dimethoxy-4-methylamphetamine, LSD, mescaline and psilocybin mimicked the training drug. Neither (+)-amphetamine nor cocaine produced mescaline-like responding; fenfluramine substituted partially for mescaline but not LSD. Because all of the phenylisopropylamine enantiomers mimicked the potent hallucinogen mescaline (10 mg/kg), these results do not support suggestions that similarities in the behavioral effects of "designer" drugs such as MDA and MDMA to those of hallucinogens are limited to (-)-MDA. They also indicate that, although LSD and mescaline may be pharmacologically similar (in other assays), these compounds do not have identical stimulus properties. PMID- 2901489 TI - Muscarinic cholinergic receptor subtype on frog esophageal peptic cells: binding and secretion studies. AB - The muscarinic receptors coupled to pepsinogen secretion on isolated frog esophageal peptic cells have been characterized using functional and radioligand binding techniques. N-[3H]methylscopolamine [( 3H]NMS) binding to intact cells was complex and indicative of a high affinity, low capacity site and a high capacity uptake site. Binding to the high capacity site was inhibited by atropine with high affinity (IC50, 3 nM) and by imipramine and propranolol with IC50 values of 70 and 270 nM, respectively. After inhibition of uptake by 30 microM propranolol, [3H]NMS bound to a single population of high affinity sites (KD, 125 +/- 16 pM), which exhibited binding site maximum of 2.1 fmol/10(6) cells, equivalent to 1260 sites/cell. Binding to these sites was reversible, stereoselective and inhibited by muscarinic receptor agonists with an order of potency: oxotremorine greater than acetylcholine greater than carbachol greater than bethanechol and by antagonists with an order of potency:atropine greater than 4-diphenylacetoxy-N-methylpiperidine methobromide greater than pirenzepine greater than AF-DX 116 (11-2[2-[[diethylamino) methyl]-1-piperidinyl]acetyl]-5, 11-dihydro-6H-pyrido[2,3-b][1,4]-benzodiazepine-6-one). Pepsinogen secretion was stimulated by the agonists with an order of potency: acetylcholine greater than or equal to carbachol greater than oxotremorine greater than bethanechol. Atropine, pirenzepine and AF-DX 116 competitively inhibited carbachol-stimulated pepsinogen secretion with pA2 values of 9.58, 7.37 and 6.68, respectively, which correlated with their log (inhibition constants) for receptor binding. By contrast, agonists with significant efficacy exhibited EC50 values which were 20 to 90 times lower than their inhibition constants for binding which suggests the possibility of "spare" muscarinic receptors. Our findings indicate that functional muscarinic receptors on peptic cells exhibit similar characteristics to the high affinity sites labeled by [3H]NMS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901491 TI - Activation of protein kinase C promotes glutamate-mediated transmission at the neuromuscular junction of the mealworm. AB - 1. Actions of protein kinase C activators, 1,2-oleoylacetylglycerol (OAG) and 12 O-tetradecanoylphorbol-13-acetate (TPA), on the glutamate-mediated neuromuscular transmission in the mealworm, Tenebrio molitor, were studied by the microelectrode current-clamp and voltage-clamp techniques. 2. The activators OAG and TPA stimulate the evoked and spontaneous transmitter releases from the presynaptic terminal, as evidenced by an increase in the quantum content estimated by the number of failures of extracellular excitatory postsynaptic potentials (EPSPs), and in the frequency of miniature EPSPs. 3. Both OAG and TPA act on the postsynaptic membrane to enhance responses to the transmitter L glutamate. Protein kinase C activators increased the apparent maximum of the ionophoretic dose-response curve for glutamate-induced depolarization, without affecting the reversal potential and the voltage-dependent decay rate for the excitatory postsynaptic current (EPSC) under voltage-clamp conditions. 4. The postsynaptic effect of OAG and TPA is distinctly different from that of activators of cyclic nucleotide-dependent protein kinases, such as octopamine, forskolin, CPT-cyclic AMP (8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate), and 8-bromo-cyclic GMP (8-bromoguanosine 3',5'-cyclic monophosphate) which decreased the postsynaptic sensitivity to L-glutamate. 5. I suggest that the responsiveness of the receptor to L-glutamate is under the control of these counteracting enzyme systems in the insect neuromuscular junction. PMID- 2901490 TI - Direct dependence studies in rats with agents selective for different types of opioid receptor. AB - The objective of this study was to describe, quantitate and compare naloxone induced abstinence syndromes in rats infused centrally (Sylvian aqueduct) with agonists that are currently the most selective for mu [( D-Ala2, MePhe4, Gly ol5]enkephalin), delta [( D-Pen2, D-Pen5]enkephalin) and kappa (3,4-dichloro-N methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]benzeneacetamide) (U-50,488H) opioid receptors, respectively. Morphine, ethylketazocine and dynorphin A served as reference compounds. After 70 hr of infusion from s.c. implanted osmotic minipumps, three levels of abstinence were associated with the injection of naloxone (3 mg/kg s.c.): 1) negligible syndromes (scores of less than 21) were obtained in rats on water or the kappa-directed ligands, U-50,488H and dynorphin A; 2) a low-to-moderate abstinence score (37-38) was recorded with rats receiving [D-Pen2, D-Pen5]enkephalin and ethylketazocine; and 3) a high abstinence score (64-73) was obtained with rats on morphine and DAGO. These results reinforce the concept of developing selective, nonbenzomorphan kappa agonists as clinically useful analgesics and emphasize that, when evaluating new analgesics, high selectivity for delta receptors does not, in itself, guarantee freedom from physical dependence. PMID- 2901492 TI - Intra-uterine perforation of Meckel's diverticulum with undescended testis (a case report). PMID- 2901493 TI - Control of cell division by sex factor F in Escherichia coli. III. Participation of the groES (mopB) gene of the host bacteria. AB - Cell division of F+ bacteria is coupled to DNA replication of the F plasmid. Two plasmid coded genes, letA (ccdA) and letD (ccdB) are indispensable for this coupling. To investigate bacterial genes that participate in this coupling, we attempted to identify the target of the division inhibitor (the letD gene product) of the F plasmid. Two temperature-sensitive growth defective mutants were screened from bacterial mutants that escaped the letD product growth inhibition that occurs in hosts carrying an FletA mutant. Phage P1-mediated transduction and complementation analysis indicated that the temperature sensitive mutations are located in the groES (mopB) gene, which is essential for the morphogenesis of several bacteriophages and also for growth of the bacteria. The nucleotide sequence of the promoter region of the gene in which the temperature-sensitive mutations had occurred was virtually identical with that of the groES gene of Escherichia coli; furthermore the sequence of the first five amino acid residues and the overall amino acid composition predicted from the nucleotide sequence of the gene match those of the purified GroES protein. The temperature-sensitive mutants did not allow the propagation of phage lambda at 28 degrees C and formed long filamentous structures without septa at 41 degrees C, as is observed in the case of groES mutants. Growth of the two groES mutants tested was not inhibited by the F plasmid with the letA mutation. These observations suggest to us that the morphogenesis gene groES plays a key role in coupling between replication of the F plasmid and cell division of the host cells. PMID- 2901494 TI - Localization of corticotropin-releasing factor, somatostatin, and vasoactive intestinal polypeptide in the parabrachial nuclei of the human brain. AB - The immunocytochemical localizations of corticotropin-releasing factor (CRF), somatostatin (SRIF), and vasoactive intestinal polypeptide (VIP) were studied in the human parabrachial nuclei (PBN) using the avidin-biotin complex (ABC) technique. The brains were obtained from seven adult male human subjects of 38-74 years. In three cases, the brains were fixed within 2 hr, in four cases within 5 hr, postmortem. All of these peptides were detected in fibers through the orocaudal extent of the lateral PBN, whereas the medial nucleus contained only CRF immunoreactive fibers. Immunoreactive fibers were distributed unevenly within the lateral nucleus with the highest density in the dorsal and much fewer in the ventral part of the lateral subdivision. The highest to lowest density of immunostained processes were detected using CRF, SRIF, and VIP antisera, respectively. Since NPB is known as an important relay nucleus for the central autonomic pathway, the presence of the above noted neuropeptides in nerve fibers in this area may suggest a neurotransmitter or neuromodulatory role of CRF, somatostatin, and VIP in certain autonomic nervous mechanism of the human brain. PMID- 2901495 TI - Localization of glial cell antigens in the brains of young normal mice and the dysmyelinating mutant mice, jimpy and shiverer. AB - Tissue sections from the brains of normal, jimpy, and shiverer mice were immunostained by the peroxidase antiperoxidase method for carbonic anhydrase (CA) and the putative astrocytic "markers" glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP). The cells in normal gray matter that immunostained with anti-CA and anti-GS were similar to one another in size and process elaboration. In the normal gray matter there were relatively few GFAP positive astrocytes. When present, these cells resembled the CA- and GS-positive cells; however, the GFAP appeared to be concentrated in the astroglial processes, as distinguished from the cell bodies. Glial cell processes, immunostained for CA or GS, surrounded blood vessels and unstained neurons in the normal gray matter. The glial cells in shiverer gray matter were similar to those in the normal gray matter. When stained for GS or GFAP, the glial cells in the jimpy gray matter appeared to be somewhat hypertrophied, and when the glial cells in this mutant were stained for CA, the nuclei appeared to be swollen. It was concluded that some of the CA-positive cells in the gray matter of the normal and of each mutant mouse brain could be astrocytes. The patterns of immunostaining in the white matter emphasized the different complements of glial cells in the mutants. In the normal and shiverer mouse corpus callosum, CA, in particular, was detected only in the oligodendrocytes, their processes, and myelin. However, the data concerning the jimpy mouse suggested that the few CA-positive cells in the corpus callosum of that mutant could be astrocytes. PMID- 2901496 TI - Modulation of tyrosine hydroxylase gene expression in rat brain and adrenals by exposure to cold. AB - The long-term changes in tyrosine hydroxylase (TH) activity induced by chronic exposure to cold in brain noradrenergic neurons of the locus coeruleus (LC) were analyzed and compared to those measured in a peripheral tissue such as adrenals. This analysis was made possible at the level of one single tissue corresponding to one animal by the use of sensitive methods that allow assay of TH activity, protein, and mRNA levels in parallel from the same homogenate. The three parameters were measured in brain structures and adrenals of rats maintained at 4 degrees C during 4 days and were compared to those of control animals kept at normal housing temperature (22 degrees C). LC of rats exposed to cold contained 200% more TH mRNA than controls. The amount of TH protein in this area rose to as much as 164% that of controls. Similarly, the activity of the enzyme increased to 140% of the normal value. Thus, these observations show that 1) the increase in TH mRNA was much higher than the increase in protein levels, and that 2) the newly synthesized molecules have about the same activity as that present under normal conditions. In contrast to the LC, no variation of these parameters was observed in the substantia nigra. In the adrenals, the variations in the different parameters were qualitatively similar to that observed in the LC, although they were quantitatively higher: TH mRNA, TH protein, and TH activity levels were respectively 330%, 182%, and 167% that of control adrenals. Altogether, these results demonstrate that exposure to cold induces an alteration in TH synthesis in brain noradrenergic neurons as well as in adrenals. PMID- 2901497 TI - Fatality from illicit phendimetrazine use. AB - Phendimetrazine is an anorectic agent which recently has been detected in three medical examiner's cases. In one instance death was attributed to this drug. Methods of detecting and identifying this drug in urine and blood are discussed. In the one instance where death was attributed to this substance, the blood concentration was 300 ng/ml. PMID- 2901498 TI - Mutation of a protein kinase C phosphorylation site in the erbB protein of avian erythroblastosis virus. AB - Tumor promoter-stimulated phosphorylation of threonine 98 of the erbB protein of avian erythroblastosis virus (AEV) correlates with inhibition of erbB-dependent mitogenesis. To more clearly define the role of phosphorylation of this residue in regulation of the activity of the erbB protein, we have constructed erbB mutations which encode alanine (Ala-98), tyrosine (Tyr-98), or serine (Ser-98) at position 98. The biosynthesis and stability of the three mutant proteins were similar to those of the wild-type erbB protein, and all three retained the ability to transform chicken embryo fibroblasts. Treatment of transformed CEF with 12-tetradecanoylphorbol-13-acetate (TPA) stimulated incorporation of 32Pi into wild-type and mutant erbB proteins and resulted in a slight decrease in the electrophoretic mobilities of all the erbB proteins. Tryptic maps of erbB phosphopeptides showed no endogenous or TPA-stimulated phosphorylation of alanine 98 or tyrosine 98 in cells transformed by the Ala-98 and Tyr-98 mutants. Analysis of tryptic phosphopeptides by high-pressure liquid chromatography revealed that TPA treatment of cells stimulated phosphorylation of other sites of the erbB protein in addition to threonine 98. A high endogenous level of phosphorylation of serine 98 of the Ser-98 mutant protein was found, and TPA treatment of cells did not result in further phosphorylation of this residue. Cells transformed by wild-type and mutant AEV were equally sensitive to TPA-dependent inhibition of growth in soft agar and TPA-dependent inhibition of [3H]thymidine incorporation. TPA treatment inhibited tyrosine phosphorylation to a similar extent in cells transformed by wild-type or Ala-98 AEV. These data indicate that phosphorylation of threonine 98 of the erbB protein is not responsible for TPA-dependent inhibition of growth of AEV-transformed cells or TPA-induced inhibition of erbB dependent tyrosine phosphorylation. TPA-stimulated phosphorylation of the erbB protein at other sites may mediate these effects. The data also show that subtle changes in a phosphorylation site (i.e., changing threonine to serine) can drastically alter recognition by protein kinases. PMID- 2901500 TI - Massive renal hemorrhage owing to polyarteritis nodosa. AB - We report a case of massive renal hemorrhage owing to unsuspected polyarteritis nodosa. The bleeding was ultimately controlled by embolization of the renal artery. The findings on renal angiography and enhanced computerized tomography were characteristic of the disorder and they should be familiar to all urologists. PMID- 2901499 TI - Genetic polymorphism of natural Epstein-Barr virus isolates from infectious mononucleosis patients and healthy carriers. AB - We analyzed Epstein-Barr virus (EBV) genomes from lymphoblastoid cell lines isolated from patients with infectious mononucleosis and from healthy subjects from California, Hawaii, and Hong Kong between 1970 and 1987. Using genetic polymorphism as epidemiological markers, we found that several genotypes of EBV cocirculate in a community and that although most EBV strains isolated from California and Southern China may be differentiated genotypically, there was no specific association between genotype and disease or time of isolation. PMID- 2901501 TI - Overview of results of randomized clinical trials in heart disease. I. Treatments following myocardial infarction. PMID- 2901502 TI - [Follow-up study of HIV-I antigen (p 24) and HIV-I antibody (gp 41, p 24) in hemophiliacs with HIV-I infection]. PMID- 2901503 TI - [Various pathophysiological conditions seen in glomerulonephritis. Urinary proteins and urinary enzymes]. PMID- 2901504 TI - [Coronary artery bypass grafting to the diagonal branch]. PMID- 2901505 TI - [Coronary artery bypass surgery utilizing an internal mammary artery graft in a 6 year-old boy with Kawasaki disease]. PMID- 2901506 TI - [Cryptorchism and germinal tumors of the testis]. PMID- 2901507 TI - [Cyclase activity, lipid peroxidation and function of the endogenous antioxidative system of the gastric mucosa during the treatment of peptic ulcer]. PMID- 2901508 TI - [Evaluation of the effect of enterosorption on the human body in a changed gaseous medium]. AB - The effect of enterosorption on biochemical and physiological parameters of 18 normal men was studied. The test subjects spent 7 days in an enclosed environment where the content of CO2 reached 3% and that of CO-40 mg/l3 during the last 8 hours of isolation. Beginning with the first day of enclosure 12 test subjects were given an enterosorbent at a dose of 0.75 g/kg 3 times a day. It is shown that a regular intake of an enterosorbent during exposure to increased concentrations of CO2 and CO affects beneficially central hemodynamics, reduces significantly plasma toxicity, content of C2-C5 hydrocarbons in the exhaled air and carboxyhemoglobin in blood. These findings may be very important for space and marine medicine because they demonstrate the efficacy of enterosorbents in protecting the human body from stress effects of an extreme environment. PMID- 2901509 TI - [Products of microbiological biodegradation of polymer materials as a factor of possible contamination of the atmosphere of hermetically sealed compartments with toxic substances]. AB - The purpose of the present investigation was to determine hygienic relevance of microbial degradation of polymers in an enclosed environment. Experiments were carried out to study the growth and development of microorganisms--molds and bacteria--on polymers. It was found that the process may be accompanied by the formation of volatile toxic substances, i.e. biodegradation products resulting from microbial decomposition of polymer components. Polymer ingredients are the major factor that determines the qualitative and quantitative composition of volatile substances. The accumulation of these substances on polymers leads to the deterioration of their sanitary-chemical properties and consequently to the contamination of the environment. It is shown that the basic products of biodegradation of polyurethane foam are ethanol and acetaldehyde and those of polyvinyl chloride plates, isooctanol (2-ethyl hexanol). The environmental parameters affect the microbial activity and therefore the rate of biodegradation processes. PMID- 2901510 TI - [Interaction between chemical substances contaminating a gaseous medium of hermetically sealed compartments]. AB - We have analyzed pertinent literature data and hypothesized that chemicals in an enclosed environment may interact (products of polymer outgassing, volatile metabolites of man). We have demonstrated that photochemical processes, thermochemical degradation and oxidation of chemicals in an enclosed atmosphere may lead to the formation of new highly toxic substances. The chemical composition of an enclosed atmosphere may be influenced by the technological processes of air purification. We have carried out experiments in a small enclosure to study ammonia and carbon dioxide interaction. When the concentration of ammonia is about 100 mg/m3, that of carbon dioxide is 2.5 vol. % and relative humidity of the atmosphere is 40-50%, the formation reaction of ammonia carbonate compounds proceeds very slowly, producing no significant changes in the environmental toxicological characteristics. It is recommended to continue the study of the interaction of chemicals at low concentrations in an enclosed environment. PMID- 2901511 TI - [Circadian rhythm of psychomotor reactions in humans exposed to the combined effects of 18-hour day schedule and increased levels of carbon dioxide]. PMID- 2901512 TI - Presynaptic alpha 2-adrenoceptors mediate inhibition of cholinergic transmission in rabbit vesical parasympathetic ganglia. PMID- 2901513 TI - Assessment of the adrenergic beta-blocking activity of Inula racemosa. AB - Inula racemosa root powder was investigated in patients with proven ischaemic heart disease. The powder prevented ST-segment depression and T-wave inversion as observed in the post-exercise electrocardiogram. The petroleum ether extract of roots lowered plasma insulin and glucose levels within 75 min of oral administration to albino rats and it significantly counteracted adrenaline induced hyperglycaemia in rats. The extract further showed negative inotropic and negative chronotropic effects on frog heart. All these findings indicate that one of the constituents of Inula racemosa may have adrenergic beta-blocking activity. PMID- 2901514 TI - [The neurobiology of anxiety: current assessment and perspectives]. PMID- 2901515 TI - Effect of carbon dioxide in acute mountain sickness: a rediscovery. AB - The effect of adding CO2 to inhaled air in six subjects with acute mountain sickness was investigated during a medical expedition to 5400 m.3% CO2 in ambient air increased ventilation and resulted in a rise in PaO2 of between 24% and 40%. There was a 9-28% increase in PaCO2 and a reduction of the respiratory alkalosis normally seen at high altitude. Symptoms of acute mountain sickness were rapidly relieved. In three subjects cerebral blood flow increased by 17-39%, so that oxygen delivery to the brain would have been considerably improved. This study confirms earlier suggestions of the beneficial effect of CO2 inhalation at high altitude. PMID- 2901517 TI - Xenobiotic metabolism in motor neuron disease. AB - Debrisoquine, carbocysteine, and paracetamol were selected as safe drugs to investigate the ability of the liver's microsomal system to oxidise carbon, oxidise sulphur, and conjugate sulphate in patients with motor neuron disease (MND), other hospital patients, and healthy volunteers. Subjects with poor sulphur-oxidising and sulphur-conjugating activities were heavily over represented in the MND group. PMID- 2901516 TI - What is the best predictor of the severity of ABO-haemolytic disease of the newborn? AB - In 80 newborn infants ABO-incompatible with their mothers, the lysis-inducing effect of the maternal IgG anti-A or anti-B antibodies in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay and the antigen density of A or B antigens on the red cells of the children were measured. On the basis of the results, the children were divided into two groups--24 children in whom increased haemolysis was to be expected, and 56 children in whom it was not. Signs of haemolysis and serological features of ABO haemolytic disease of the newborn (ABO HDN) were compared in these two groups and a control group of 120 ABO-compatible infants. The effect of the maternal antibodies in the ADCC assay, the titres of maternal IgG anti-A or anti-B antibodies, the results of the direct antiglobulin test on the red cells in the cord blood, and the titre of IgG anti-A or anti-B antibodies in the serum of the infants were compared for their ability to predict the severity of ABO-HDN. This was also done for the combination of the ADCC assay results plus the A or B antigen density and the direct antiglobulin test plus the titre of maternal IgG anti-A or anti-B antibodies. The ADCC assay with maternal serum was the most sensitive assay to predict ABO-HDN, and the combination of the ADCC assay with A or B antigen density determination the most specific test. PMID- 2901518 TI - Passive immunoneutralization of human immunodeficiency virus in patients with advanced AIDS. AB - Infusions of 55-500 ml plasma from one of two donors selected for high anti-p24 antibody titre and neutralising capacity were given to six patients with advanced AIDS. Human immunodeficiency virus (HIV) antigenaemia cleared immediately and the recipients' serum acquired the HIV antibody profile of the donor together with HIV neutralising activity. The passive antibody effects persisted for up to eleven weeks depending upon the volume of plasma given, which had a half-life of about 12 days. The infusions were followed by fewer symptoms, a transient increase in T lymphocytes, a reduction in the frequency of opportunistic infections, and a decline in the rate at which HIV could be cultured from plasma or lymphocytes. PMID- 2901520 TI - Guillain-Barre syndrome. PMID- 2901519 TI - Effect of cigarette smoking on cervical epithelial immunity: a mechanism for neoplastic change? AB - Langerhans' cells in cervical epithelium in colposcopic biopsy specimens were identified by immunocytochemical staining for S100 protein and T6 (CD1) antigen, and their density was quantified. Possible cofactors for the development of cervical neoplasia were examined for any effect on the cell counts per unit area. Current cigarette smoking was associated with a significant decrease in the Langerhans' cell population in both normal epithelium and lesions due to cervical intraepithelial neoplasia. Ex-smokers tended to have cell counts between those of smokers and non-smokers. There was a dose-response relation between number of cigarettes smoked daily and effect on cell counts. These findings of a local immunological effect of smoking on cervical epithelium may explain the means by which cigarette smoking contributes to the development of cervical neoplasia. PMID- 2901521 TI - Do T cells cause IDDM? PMID- 2901522 TI - Limb salvage surgery. PMID- 2901523 TI - Searching MEDLINE. PMID- 2901524 TI - Who needs an intragastric balloon for weight reduction? PMID- 2901525 TI - Risk of cancer among children exposed in utero to A-bomb radiations, 1950-84. AB - This study examines the risk of cancer (incidence) over 40 years among the in utero exposed survivors of the atomic bombing of Hiroshima and Nagasaki, and adds eight years of follow-up to a previous report confined to mortality. Only two cases of childhood cancer were observed among these survivors in the first 14 years of life; both had been heavily exposed. Subsequent cancers have all been of the adult type. Not only did the observed cancers occur earlier in the 0.30 + Gy dose group than in the 0 Gy dose group but also the incidence continues to increase, and the crude cumulative incidence rate, 40 years after the A-bombing, is 3.9-fold greater in the 0.30 + Gy group. In the observation period 1950-84, based on the absorbed dose to the mother's uterus as estimated by the 1986 dosimetry system (DS86), the relative risk of cancer at 1 Gy is 3.77 with a 95% confidence interval of 1.14-13.48. For the entire 0.01 + Gy dose group the average excess risk per 10(4) person-year-gray is 6.57 (0.07-14.49) and the estimated attributable risk is 40.9% (2.9-90.2%). These results, when viewed in the perspective of fetus doses, suggest that susceptibility to radiation-induced cancers is higher in prenatally than in postnatally exposed survivors (at least those exposed as adults). However, definitive conclusions must await further follow-up studies. PMID- 2901526 TI - Evaluation of ultraviolet light for disinfection of hospital water contaminated with Legionella. AB - An epidemic of nosocomial Legionella micdadei pneumonia occurred among renal transplant patients in the University of Virginia hospital between 1978 and 1982. Although no further cases were diagnosed after 1982, filters and ultraviolet light (UVL) fittings were installed in 1985 as an attempt to disinfect water piped to rooms of transplant patients, because of concern about persistence of L micdadei in hospital water. Water samples were obtained from eight UVL-treated rooms and eight control rooms. 26 of 95 control samples were culture positive for L micdadei compared with 0 of 71 samples of filtered, UVL-treated water (p less than 0.0001, Fisher's exact test). After the UVL fitting and filter had been bypassed because of a leak, 9 of 33 samples from the UVL rooms were positive (p less than 0.0001). These data suggest that UVL treatment may be useful in continuous disinfection of water in the hospital rooms of high-risk patients. PMID- 2901527 TI - Implications of the new genetics for screening for cystic fibrosis. PMID- 2901528 TI - Could we safely negotiate a treaty banning all nuclear tests? PMID- 2901529 TI - Yohimbine alters regional cerebral blood flow in panic disorder. PMID- 2901530 TI - Surgical management of biliary atresia. PMID- 2901531 TI - Diet and cyclical mastopathy. PMID- 2901532 TI - False-positive results and the polymerase chain reaction. PMID- 2901533 TI - Branched-chain aminoacids in amyotrophic lateral sclerosis. PMID- 2901534 TI - Family outbreak of Chlamydia trachomatis. PMID- 2901535 TI - Variation in serum cholesterol. PMID- 2901536 TI - Gallstones and glaciers: hypothesis melting at the equator. PMID- 2901537 TI - Safety of midazolam. PMID- 2901538 TI - Safety of mianserin. PMID- 2901539 TI - Progesterone for premenstrual exacerbations of asthma. PMID- 2901540 TI - Reye's syndrome and aspirin. PMID- 2901541 TI - Subcutaneous erythropoietin. PMID- 2901542 TI - Early detection of breast cancer. PMID- 2901543 TI - Drug regulation in the EEC. PMID- 2901545 TI - Sunlight and drinking water. PMID- 2901544 TI - Health education and traditional cultures. PMID- 2901546 TI - Resource allocation. PMID- 2901547 TI - Measuring cardiac output. PMID- 2901548 TI - Monitoring of cyclosporin by monoclonal radioimmunoassay. PMID- 2901549 TI - Clinical heterogeneity of central pontine myelinolysis. PMID- 2901550 TI - Borna disease virus-specific antibodies in patients with HIV infection and with mental disorders. PMID- 2901551 TI - Zidovudine-associated myopathy. PMID- 2901552 TI - AIDS case definitions for African children. PMID- 2901553 TI - HIV antigen and virus-safety studies. PMID- 2901554 TI - Urokinase versus tissue plasminogen activator in pulmonary embolism. PMID- 2901555 TI - Cardiac metabolism during exercise measured by magnetic resonance spectroscopy. PMID- 2901556 TI - Guthrie spots for DNA-based carrier testing in cystic fibrosis. PMID- 2901557 TI - Toxic shock syndrome after a minor surgical procedure. PMID- 2901558 TI - Falling death rates from bronchitis. PMID- 2901559 TI - Joint hypermobility syndrome and anxiety disorders. PMID- 2901560 TI - Laparoscopic management of ectopic pregnancies. PMID- 2901561 TI - Blood group substances in pneumococcal vaccine. PMID- 2901562 TI - Percutaneous angioscopy of peripheral arteries. PMID- 2901563 TI - AIDS in the UK and globally. PMID- 2901564 TI - Wild chimps rocket statisticians. PMID- 2901565 TI - Effects of prolonged naloxone infusion in septic shock. AB - Fourteen patients suffering sixteen episodes of septic shock requiring inotrope and/or vasopressor support were randomised to receive a 30 micrograms/kg naloxone intravenous bolus followed by a 30 micrograms/kg/h infusion or an equivalent volume placebo bolus and infusion for 8-16 h in a double-blind study. pH and pulmonary wedge pressure were kept constant, and inotrope and/or vasopressor were titrated to maintain a preselected mean blood pressure. Inotrope/vasopressor requirements in the naloxone-treated group were significantly lower than those in the control group at 8 h (eight patients in each group, p less than 0.005) and at 16 h (five patients in each group, p less than 0.02). Late but significant improvements in stroke volume (p less than 0.02) and heart rate (p less than 0.05) were also noted in the eight naloxone-treated patients. PMID- 2901566 TI - Randomised, double-blind, placebo-controlled trial of ditiocarb sodium ('Imuthiol') in human immunodeficiency virus infection. AB - 83 patients with human immunodeficiency virus (HIV) infection (CDC groups II, III, or IV-A) were randomised in a crossover trial of sodium diethyldithiocarbamate (ditiocarb sodium, 'Imuthiol') (10 mg/kg body weight given orally once a week) against placebo. Each arm of the trial lasted 16 weeks. The disease did not progress to CDC-defined acquired immunodeficiency syndrome in the ditiocarb group but did so in 4 patients in the placebo group (3 between week 0 and 16, 1 between week 17 and 32). Ditiocarb was also associated to a significantly greater extent than placebo with relief of constitutional symptoms, improvement in clinical status (including shrinkage of enlarged spleen and lymph nodes), and improvement in immune function (as measured by CD4+ cell count and skin test reactivity). When placebo was replaced by ditiocarb, similar improvements were observed, whereas symptoms slowly reappeared and CD4+ cell levels progressively declined when ditiocarb treatment was replaced by placebo. PMID- 2901567 TI - Correlation of plasma interleukin 1 levels with disease activity in rheumatoid arthritis. AB - The mean plasma level of interleukin 1 beta (IL-1 beta), measured by immunoassay, was significantly higher in 51 patients with rheumatoid arthritis (RA) than in 21 healthy controls of similar age. Further, in the RA group, plasma IL-1 beta correlated positively with Ritchie joint index, pain score, and erythrocyte sedimentation rate and correlated negatively with haemoglobin concentration. In individual patients with active disease who had serial measurements, plasma IL-1 beta also correlated with clinical disease activity. These results support the idea that IL-1 beta has a central role in the pathogenesis of RA. PMID- 2901568 TI - Hypohaptoglobinaemia as an epidemiological and clinical indicator for malaria. Results of two studies in a hyperendemic region in West Africa. AB - Hypohaptoglobinaemia is a common phenomenon in tropical countries, where it is probably due to malaria-induced haemolysis. Two studies were carried out in a hyperendemic zone of West Africa to test its specificity and usefulness as an epidemiological indicator for measuring malaria endemicity. The first study evaluated the prevalence of hypohaptoglobinaemia before and after courses of antimalarial chemotherapy of varying duration. The second monitored haptoglobin levels in an untreated population during a whole year to compare its seasonal variations with those of several classic indicators of malaria. These studies suggest that in regions where malaria is endemic the prevalence of hypohaptoglobinaemia could be as useful an indicator as the parasitic index but would be much easier to establish and to monitor. PMID- 2901569 TI - Effect of electrical nerve stimulation on healing of ischaemic skin flaps. AB - Blood circulation was measured by laser doppler flowmetry in fasciocutaneous flaps of 24 patients who underwent reconstructive surgery for mammary carcinoma. 19 of the 24 patients had clinical signs of deficient circulation in the flaps. 14 patients were treated with electrical nerve stimulation (ENS) and 10 with placebo-ENS. Varying degrees of necrosis developed in 8 of the 10 patients who received placebo stimulation but in none of those treated with ENS. In the 5 patients with good capillary refilling and no signs of stasis or oedema before treatment, only minor increases in blood flow occurred after ENS. PMID- 2901570 TI - Treatment of anismus in intractable constipation with botulinum A toxin. AB - In seven patients with anismus the striated sphincter muscle complex was selectively weakened by local injection of Clostridium botulinum type A toxin. Symptom scores improved significantly and correlated with a significant reduction in the maximum voluntary and canal squeeze pressure and a significant increase in the anorectal angle on straining. Botulinum A toxin seems to be promising treatment for some patients with anismus. PMID- 2901571 TI - Genetic markers for neurofibromatosis. PMID- 2901572 TI - Salmonella enteritidis phage type 4: chicken and egg. PMID- 2901573 TI - Virological screening for herpes simplex virus during pregnancy. PMID- 2901574 TI - Optimistic strategy for prevention. PMID- 2901575 TI - Epstein-Barr virus and T-cell lymphoma. PMID- 2901578 TI - A view from a nation less likely to be a target for nuclear weapons. PMID- 2901576 TI - Campylobacter pylori in abattoir workers: is it a zoonosis? AB - Sera from 98 abattoir workers were tested for IgG to Campylobacter pylori, C jejuni, and klebsiella. Clerical workers had significantly lower C pylori and C jejuni IgG titres than any of the groups in direct contact with freshly cut animal parts. No difference was found for antibodies to klebsiella. 28 non clerical workers with high-titre C pylori IgG consented to upper gastrointestinal endoscopy. C pylori associated gastritis was found in all 28, and four weeks of colloidal bismuth subcitrate (240 mg twice daily) was prescribed. On repeat testing at three months all showed a decrease in IgG titres to C pylori but not to C jejuni, whereas 18 untreated non-endoscoped workers showed no change. These findings raise the possibility that C pylori infection is a zoonosis. PMID- 2901577 TI - Death takes a holiday: mortality surrounding major social occasions. AB - To determine whether death can be postponed until after an important social occasion the number of deaths before and after the Jewish holiday of Passover (1966-84) were compared. Passover was chosen for study because it allows comparison of the participating and non-participating (control) groups, and it moves around the calendar (thus allowing separation of the effects of the holiday from the effects of the seasons). In the total Jewish sample (n = 1919), the number of deaths was lower than expected in the week before Passover and higher than expected in the week after (p = 0.045). This dip-peak pattern of mortality was concentrated among people with unambiguously Jewish surnames (p = 0.003) and did not appear in various control groups, including Blacks, Orientals, and Jewish infants. The pattern was most pronounced in the years when the holiday fell on a weekend, when it is most likely to be celebrated by the largest number of people (n = 183; p = 0.001). This pattern was statistically significant by binomial tests and by regression analyses of the data. The Passover pattern of mortality was found in each of the three leading causes of death. PMID- 2901580 TI - Energy expenditure and cystic fibrosis. PMID- 2901579 TI - No fault compensation Finnish style. PMID- 2901582 TI - Resting energy expenditure and energy intake in cystic fibrosis. PMID- 2901581 TI - Thioridazine: a radiation enhancer in advanced cervical cancer? PMID- 2901583 TI - Growth during early teenage pregnancy. PMID- 2901585 TI - Self-measurement of blood pressure. PMID- 2901584 TI - Sleeping position, cot mattresses, and cot deaths. PMID- 2901586 TI - Continuous tissue plasminogen activator infusion to maintain patency of recurrently narrowing coronary artery. PMID- 2901587 TI - Aspirin, infarction, and platelet/vessel-wall interactions. PMID- 2901588 TI - Is absence of atheroma in Down syndrome due to decreased homocysteine levels? PMID- 2901589 TI - Profound fetal thrombocytopenia in Rhesus disease: serious hazard at intravascular transfusion. PMID- 2901591 TI - Respiratory tract chlamydial infection and importation of psittacine birds. PMID- 2901590 TI - Simple clinical signs for diagnosis of acute lower respiratory infections. PMID- 2901593 TI - The enemy system. PMID- 2901592 TI - Health priorities and the developing world. PMID- 2901594 TI - Vitamins, minerals, and IQ. PMID- 2901595 TI - Prenatal diagnosis of cystic fibrosis where single affected child has died. PMID- 2901596 TI - Amyloid precursor protein in senile plaques of Alzheimer disease. PMID- 2901597 TI - Herpesviruses as co-factors in AIDS. PMID- 2901598 TI - False-positive Paul-Bunnell test in HIV seroconversion. PMID- 2901599 TI - Cimetidine (but not ranitidine or famotidine) affects histamine determination. PMID- 2901600 TI - CMV, HIV, and the pancreas. PMID- 2901601 TI - Another strain of methicillin-resistant Staphylococcus aureus epidemic in London. PMID- 2901602 TI - High-dose adrenaline and cardiac arrest. PMID- 2901603 TI - Spaced administration of antibiotic combinations to eliminate pseudomonas from sputum in cystic fibrosis. PMID- 2901604 TI - Patch testing and menstruation. PMID- 2901605 TI - Serological differences between verocytotoxin 2 and shiga-like toxin II. PMID- 2901606 TI - Rapid spontaneous postpartum clearance of Plasmodium falciparum parasitaemia in African women. PMID- 2901607 TI - Anonymous testing for HIV. PMID- 2901608 TI - UK coordinated AIDS research. PMID- 2901609 TI - Circadian variation of total ischaemic burden and its alteration with anti anginal agents. AB - 6264 hours of ambulatory ST segment monitoring of 150 unselected patients with proven coronary artery disease, who were off all routine anti-anginal treatments, showed 598 ischaemic episodes, of which 446 (75%) were silent (symptom-free). Most (68%) ischaemic episodes occurred between 0730 and 1930, with a peak in the morning and a lesser peak in the evening. Two subgroups were studied further in double-blind controlled trials: 33 patients had a total of 1313 hours of ST segment monitoring while treated with nifedipine; and 41 patients a total of 1581 hours while treated with atenolol. Nifedipine did not alter the circadian pattern of ischaemic episodes; atenolol abolished the morning peak, and the peak incidence of ischaemia then occurred in the evening. Circadian patterns for total duration of ischaemic episodes corresponded closely to those of episodes of ischaemia, and were similarly altered by treatment. The circadian pattern of silent ischaemic episodes and their total duration were very similar to those of total ischaemia for the group as a whole and the different subgroups. This circadian distribution of ischaemic episodes and the observed changes with treatment resemble the reported circadian variation of acute myocardial infarction and sudden death. PMID- 2901610 TI - Controlled clinical trial of complete open surgical drainage and of prednisolone in treatment of tuberculous pericardial effusion in Transkei. AB - 240 patients with active tuberculous pericardial effusion received a 4-drug daily antituberculosis regimen for 6 months and have been studied for 24 months or longer. Those willing were randomly allocated to open pericardial biopsy and complete drainage of pericardial fluid on admission or percutaneous pericardiocentesis as required. All patients were randomly allocated to prednisolone or matching placebo for the first 11 weeks, on a double-blind basis. Complete open drainage on admission abolished the need for pericardiocentesis (p less than 0.01) but did not influence the need for pericardiectomy for subsequent constriction or the risk of death. Among patients who did not have open drainage on admission, 2 (3%) of 76 given prednisolone compared with 10 (14%) of 74 given placebo died of pericarditis (p less than 0.05), 6 (8%) and 9 (12%) respectively required pericardiectomy, 7 (9%) and 17 (23%) repeat pericardiocentesis (p less than 0.05), and 3 (4%) and 7 (9%) open surgical drainage. By 24 months, apart from the 16 who died from pericarditis, all but 3 patients (2%) had a favourable status. PMID- 2901612 TI - Prevention of disuse muscle atrophy by means of electrical stimulation: maintenance of protein synthesis. AB - The effect of percutaneous electrical stimulation in preventing immobilisation induced muscle atrophy was determined from measurements of quadriceps mass, composition, and rate of protein synthesis in seven men who had a fracture of one tibia immobilised in a long-leg cast for 6 weeks. These features were compared with those of fourteen men with similar injuries who did not use an electrical stimulator. In men who did not use the stimulator, quadriceps cross-sectional area (CSA) at midthigh, measured by ultrasonography, fell by a mean (SD) 17 (10)% and the rate of muscle protein synthesis was 23 (10)% lower on the immobilised than on the control side (0.037 [0.016] vs 0.048 [0.02]%/h). In contrast, in those who used the stimulator, quadriceps CSA (55.5 [7.3]) cm2 control leg, 50.9 [9.0] cm2 immobilised leg) and the rate of muscle protein synthesis (0.053 [0.009] %/h control leg, 0.059 [0.012] %/h immobilised leg) were similar on the two sides. The results suggest that brief periods of low-voltage percutaneous electrical stimulation will reduce quadriceps atrophy secondary to knee immobilisation, and that the mechanism includes prevention of the fall in muscle protein synthesis that usually occurs on immobilisation. PMID- 2901611 TI - Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus. AB - In a preliminary study, carriers of hepatitis B virus were treated with a preparation of the plant Phyllanthus amarus for 30 days. 22 of 37 (59%) treated patients had lost hepatitis B surface antigen when tested 15-20 days after the end of the treatment compared with only 1 of 23 (4%) placebo-treated controls. Some subjects have been followed for up to 9 months. In no case has the surface antigen returned. Clinical observation revealed few or no toxic effects. The encouraging results of this preliminary study recommend continued evaluation of this plant and the active principles isolated from it. PMID- 2901614 TI - Selective fetal reduction. PMID- 2901613 TI - Cotside measurement of cerebral blood flow in ill newborn infants by near infrared spectroscopy. AB - A new method of quantifying cerebral blood flow which allows repeated cotside measurements is described. 31 observations were made on nine ill, mostly very preterm, infants. Cerebral blood flow was usually about 18 ml.100 g-1.min-1, but ranged from 7 ml.100g-1.min-1 (after the administration of indomethacin to a very preterm infant) to 33 ml.100 g-1.min-1 in a birth-asphyxiated post-term infant. PMID- 2901615 TI - Diuretics or paracentesis for ascites? PMID- 2901616 TI - Measuring stiffness in rheumatoid arthritis. PMID- 2901617 TI - A diamond jubilee. PMID- 2901618 TI - Genetics of pre-eclampsia. PMID- 2901621 TI - Nuclear winter. PMID- 2901622 TI - A threat to medicine's professional mandate. PMID- 2901620 TI - Virucidal treatment of clotting factor concentrates. PMID- 2901623 TI - Value of prolonged breastfeeding. PMID- 2901619 TI - Association of sporadic listeriosis with consumption of uncooked hot dogs and undercooked chicken. AB - In 1986-87 the Centers for Disease Control conducted an active population-based survey of Listeria monocytogenes infections in six regions of the United States. Listeriosis was reported in 154 patients: one-third of cases were perinatal and the remaining two-thirds occurred in the elderly and immunosuppressed. 28% of cases were fatal. 82 cases and 239 controls matched for age and underlying disease were enrolled in a study of risk factors for listeriosis. Cases were significantly more likely than controls to have eaten uncooked hot dogs or undercooked chicken, with 20% of the overall risk of listeriosis attributable to consumption of these foods. No other risk factors were identified. PMID- 2901624 TI - Amenorrhoea/depression in famine. PMID- 2901625 TI - Acetylcholine sweatspot test. PMID- 2901626 TI - Pregnancy after transfer of sperm under zona. PMID- 2901627 TI - Syncope and vomiting. PMID- 2901628 TI - Two rabies deaths after corneal grafts from one donor. PMID- 2901629 TI - Malaria chemoprophylaxis and traveller's weight. PMID- 2901630 TI - Do health workers recognise tuberculosis in Burkina Faso? PMID- 2901631 TI - Clinical signs of pneumonia in children. PMID- 2901632 TI - Glucose transporter gene and non-insulin-dependent diabetes. PMID- 2901633 TI - Resolution, by DNA probes, of uncertain diagnosis of inheritance of hypercholesterolaemia. PMID- 2901634 TI - Timing of seroconversion in Legionnaires' disease. PMID- 2901635 TI - Screening for toxoplasma in pregnancy. PMID- 2901636 TI - Cyanide and fire victims. PMID- 2901637 TI - Infant feeding and childhood cancer. PMID- 2901639 TI - Thromboembolism and air travel. PMID- 2901638 TI - Hypovitaminosis A and acne. PMID- 2901640 TI - Health care inequity in USA. PMID- 2901641 TI - Right to die. PMID- 2901642 TI - Time-expired drugs. PMID- 2901643 TI - Medical defence premiums. PMID- 2901644 TI - Consent to AIDS testing. PMID- 2901645 TI - Intranasal glucagon for hypoglycaemia. PMID- 2901646 TI - Almitrine and peripheral nerve function. PMID- 2901647 TI - Staphylococcal peritonitis following selective decontamination of digestive tract. PMID- 2901648 TI - Clinical cure of haemophilia A by liver transplantation. PMID- 2901649 TI - Multiple sclerosis: a T-cell disease? PMID- 2901650 TI - Neonatal necropsy in developing countries. PMID- 2901651 TI - Dialysis amyloidosis with massive popliteal deposition of beta 2-microglobulin amyloid. PMID- 2901652 TI - Risk of relapse upon withdrawal of cyclosporin therapy for psoriasis. PMID- 2901653 TI - Dietary modification as cause of anticoagulation instability. PMID- 2901654 TI - Human herpesvirus 6 and the Henle-Koch postulates. PMID- 2901655 TI - Malignant thyroid tumours following childhood cancer. PMID- 2901656 TI - Routine one-stage ultrasound screening in pregnancy. PMID- 2901657 TI - Williams syndrome and renal failure. PMID- 2901658 TI - The extension of AIDS. PMID- 2901659 TI - Alpha-adrenergic agonists stimulate neonatal glucose production less than beta adrenergic agonists in the lamb. AB - Epinephrine, a catecholamine with both alpha (alpha)- and beta (beta)-adrenergic agonist effects, may produce clinical hyperglycemia in the adult by increasing glucose production and decreasing glucose clearance. However, the relative contribution of alpha v beta adrenergic agonists in control of neonatal glucose kinetics has not been defined. Twenty-three term lambs (weighing 4.4 +/- 0.2 kg, mean +/- SEM, and aged 3.8 +/- 0.4 days) were infused with 0.9% NaCl at 0.6 mL.kg 1 min-1 + 100 microCi/kg D[6-3H]-glucose by prime plus constant infusion for 210 minutes. Ra (rate of production) was measured during infusion of variable doses of epinephrine with or without variable doses of propranolol, a competitive beta adrenergic antagonist to isolate the alpha-adrenergic agonist effects. All basal kinetic data were comparable. Under conditions of epinephrine infusion, the plasma glucose concentration increased from 95 +/- 10 mg/dL to 129 +/- 18 mg/dL (50 ng.kg-1 min-1 epinephrine; P less than .0001) and from 85 +/- 6 mg/dL to 253 +/- 8 mg/dL (500 ng.kg-1 min-1 epinephrine; P less than .00001) compared with controls (96 +/- 7 mg/dL to 95 +/- 8 mg/dL). When epinephrine and propranolol were infused simultaneously, plasma glucose concentration increased from 95 +/- 10 mg/dL to 122 +/- 12 mg/dL (50 ng.kg-1 min-1 epinephrine + 1.1 micrograms.kg-1 min-1; P less than .0001) and from 78 +/- 9 mg/dL to 134 +/- 12 mg/dL (500 ng.kg 1 min-1 epinephrine + 11 micrograms.kg-1 min-1; P less than .0001) compared with controls (no epinephrine, no propranolol).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901660 TI - Functional and structural homology among regulatory cistrons of pili-adhesin determinants in Escherichia coli. AB - Expression of the digalactoside-binding Pap pili involves two trans-acting regulatory genes, papB and papI. Using pap-lac operon fusions and DNA hybridization probes derived from pap DNA we tested whether or not other pili adhesin determinants from different Escherichia coli strains encode homologs to the pap regulatory genes. Digalactoside-specific clones of serotypes F72 and F11 complemented papB and papI mutants of the Pap (serotype F13) clone and DNA hybridization analysis showed that the clones are homologous in the DNA sequences encoding the two regulatory genes. Similar results were obtained with an S-pili determinant which mediates binding to sialic acid-containing receptors and the findings suggest that the regulatory regions may be more conserved than other genes in different pili-adhesin gene clusters. Determinants for type 1-pili (mannose-specific binding) and for pili associated with enterotoxigenic E. coli (K88, K99, CFAI, CFAII) did not appear to contain DNA sequences homologous to papB or papI. E. coli strain J96, which was the origin of the pap DNA, was found to carry two additional copies of papB-papI homologous sequences in the chromosome. In strains expressing more than one kind of pili the trans-active gene products thereby may allow for regulatory interaction between separate pili adhesin gene systems. PMID- 2901661 TI - Restriction fragment polymorphism in the sex-determining region of the Y chromosomal DNA of European wild mice. AB - Using 32P-labeled probe consisting mainly of (GATA)n we have shown that a male specific Alu1 DNA blot pattern which defines the Y chromosome sex-determining locus in inbred mice is highly polymorphic in wild mice, indicating substantial sequence evolution in this region under field conditions. In all cases examined by in situ hybridization, the region concerned is paracentromeric. In contrast, the blot pattern of another probe (M 34) which detects repeated sequences specific to the mouse Y chromosome but outside the sex-determining locus, remains constant between different isolates. PMID- 2901662 TI - Excitatory amino acid receptors expressed in Xenopus oocytes: agonist pharmacology. AB - The properties of excitatory amino acid (EAA) receptors transplanted into Xenopus oocytes were investigated by voltage clamp 48 hr to 5 days after oocytes had been injected with mRNA isolated from rat brain. The application of EAA agonists to mRNA-injected cells, but not to uninjected or water-injected cells, produced several different inward currents, two of which are characteristic of neuronal EAA receptors. Currents with properties expected from activation of N-methyl-D aspartate (NMDA) receptors were evoked by L-glutamate (EC50 = 2.3 microM), D aspartate (10 microM), L-aspartate (13 microM), NMDA (31 microM), and ibotenate (35 microM). Inward currents activated by these agonists were blocked by Mg2+ in a voltage-dependent manner and antagonized by 10-50 microM D-2-amino-5 phosphonovaleric acid (D-APV). The D-APV block was not voltage dependent. A second type of inward current was produced by kainate, domoate, (RS)-alpha-amino 3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and L-glutamate. This smooth inward current was insensitive to Mg2+ and D-APV. L-Glutamate and domoate were equipotent for activating this current (EC50 = 14 microM) whereas kainate was less potent (98 microM). The kainate potency was somewhat voltage dependent, inasmuch as the EC50 was 33% lower when measured at +38 mV than when measured at 60 mV in the same cells. Quisqualate (50 microM) and AMPA (50 microM) drastically reduced the kainate current, suggesting these agonists also interact with this receptor. Some mRNA preparations encoded only receptors for the kainate response, which argues for distinct NMDA and non-NMDA receptors. A third type of inward current was produced by quisqualate. This current, consisting of oscillating and smooth components, was carried by chloride and not evoked by AMPA, suggesting it is not likely caused by activation of the conventional neuronal quisqualate receptor. The utility of the oocyte preparation for quantitative pharmacological studies of EAA receptors is discussed. PMID- 2901663 TI - Opiate binding in calf thalamic membranes: a selective mu 1 binding assay. AB - In the present study, we examined the binding of [3H][D-Ala2,D-Leu5]enkephalin ([ 3H]DADL) to bovine thalamic membranes. Scatchard plots were linear with a KD of 0.7 nM. However, competition experiments suggested binding heterogeneity. Approximately 20% of [3H]DADL binding was easily inhibited by [D-Pen2,D Pen5]enkephalin (DPDPE) and was insensitive to morphine, implying labeling of delta receptors. The remaining 80% of binding was quite sensitive to both morphine and [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAGO) and insensitive to DPDPE, consistent with a mu receptor. However, this binding did not correspond to classical morphine-selective mu receptors. Unlike morphine-selective receptors, this binding had similar affinities for morphine, DAGO, DADL and [D Ser2,Leu5]enkephalin-Thr6 (DSLET). In addition, it was far more sensitive to naloxonazine's wash-resistant inhibition and magnesium-induced enhancement of binding than either the morphine-selective (mu 2) or delta sites. [3H]DSLET binding yielded results very similar to those using [3H]DADL. In conclusion, approximately 80% of [3H]DADL binding in thalamus corresponds to a mu receptor distinct from the classical morphine-selective site. Based upon the results of our studies, we feel that this binding represents mu 1 receptors. DPDPE (10 nM) can effectively inhibit the binding of [3H]DADL to delta receptors, leaving a relatively homogeneous labeling of mu 1 sites. The availability of this selective binding assay should facilitate additional studies of mu 1 receptors. PMID- 2901664 TI - Evidence for alpha 1-adrenergic receptor internalization in DDT1 MF-2 cells following exposure to agonists plus protein kinase C activators. AB - Agonist-induced sequestration and internalization of alpha 1-adrenergic receptors were examined in DDT1 MF-2 cells. Pretreatment of cells with epinephrine or norepinephrine alone, but not with phorbol 12-myristate 13-acetate alone, resulted in a marked decrease in [3H]prazosin binding to intact cells at 4 degrees. These pretreatments resulted in little or no change in the fraction of alpha 1-adrenergic receptors exhibiting limited accessibility to the hydrophilic competing ligand epinephrine in short-time competition binding assays with intact cells and little or no change in the subcellular distribution of alpha 1 adrenergic receptors between the plasma membrane and light vesicle compartments as assessed by sucrose density gradient centrifugation assays. Pretreatment with a combination of agonist plus phorbol 12-myristate 13-acetate resulted in a greater decrease in [3H]prazosin binding at 4 degrees than was observed when cells were pretreated with agonist alone, induced the conversion of about half of cell surface alpha 1-adrenergic receptors to a form exhibiting limited accessibility to epinephrine in short-time assays, and induced a shift of about half of alpha 1-adrenergic receptors from the plasma membrane fraction to a light vesicle fraction on sucrose density gradients. A similar shift of alpha 1 adrenergic receptors was observed on sucrose density gradients after exposure to agonist plus either mezerein or beta-phorbol didecanoate, but not with agonist plus alpha-phorbol didecanoate, indicating involvement of protein kinase C. These results suggest that pretreatment with agonist alone induces the sequestration of alpha 1-adrenergic receptors into a compartment that is inaccessible to [3H]prazosin at 4 degrees but that is accessible to hydrophilic ligands at 37 degrees and remains associated with the plasma membrane. In contrast, alpha 1 adrenergic receptors are apparently internalized from the plasma membrane to a separate compartment, presumably an intracellular vesicle, when cells are pretreated simultaneously with a combination of agonist plus a protein kinase C activator. PMID- 2901665 TI - The potency and kinetics of the beta-adrenergic receptors on human neutrophils. AB - The binding to catecholamines to the beta-adrenergic receptors on human polymorphonuclear leukocytes rapidly inhibits cell responses stimulated by chemoattractant ligands. As a first step in understanding the mechanism of the inhibition, we investigated the number of beta-receptors required to optimally block superoxide anion production, a response that is measured kinetically by a convenient spectrophotometric assay for the reduction of cytochrome c. We found that after blockade of 50-60% of the beta-adrenergic receptors with an irreversible antagonist, maximal inhibition of the response was still elicited by isoproterenol (ISO). Next we investigated the kinetics with which superoxide generation is inhibited. We found that half-maximal inhibition was observed at 3 x 10(-8) M ISO, which approximates the Kd because many of the receptors are involved. Cell responsiveness recovered when propranolol was added between the time of ISO and chemoattractant addition. From the recovery we estimated that the half-time for ISO dissociation is less than 10 sec. Finally, we examined the rate at which cell responses decay following ISO administration after chemoattractant. Optimal rates of inhibition, turning off oxidant production in seconds, occur at ISO concentrations greater than or equal to 3 x 10(-7) M. Taken together, these observations are consistent with an association rate constant for ISO estimated to be greater than or equal to 10(8) M-1min-1 and a dissociation rate constant greater than or equal to 4 min-1. These results are discussed in terms of the available data concerning the binding of agonists to beta-adrenergic receptors. PMID- 2901666 TI - Effect of tumor necrosis factor on acetyl-coenzyme A carboxylase gene expression and preadipocyte differentiation. AB - Tumor necrosis factor (TNF) is secreted by macrophages in response to various stimuli and blocks lipid accumulation during the conversion of preadipocytes to adipocytes in culture. In the present report, we investigate the effect of recombinant TNF on the expression of acetyl-coenzyme-A (CoA) carboxylase, the rate-limiting enzyme for long-chain fatty acid biosynthesis. We used a preadipocyte cell line, 30A-5, derived from 10T1/2 mouse fibroblasts after treatment with 5-azacytidine. Treatment of the preadipocyte cell line with dexamethasone and insulin triggers the conversion of these cells to mature adipocytes as evidenced by the accumulation of lipid. The mRNA and enzyme levels of acetyl-CoA carboxylase as well as the enzyme activity increase markedly during the conversion process. TNF prevents the conversion of preadipocytes to adipocytes with a concomitant inhibition in the accumulation of acetyl-CoA carboxylase mRNA and decrease in enzyme activity. This observed reduction in acetyl-CoA carboxylase mRNA levels is reversible upon removal of TNF. Acetyl-CoA carboxylase mRNA levels and enzyme activity also decrease when fully differentiated adipocytes are exposed to TNF but to a much lesser extent. These results suggest that TNF affects de novo lipid synthesis in part by altering the mRNA levels of acetyl-CoA carboxylase. PMID- 2901667 TI - Regulation of two c-erbA messenger ribonucleic acids in rat GH3 cells by thyroid hormone. AB - There is recent evidence suggesting that c-erbA is the thyroid hormone nuclear receptor, and that there may be multiple c-erbA genes. We investigated the effect of T3 on two c-erbA mRNAs present in GH3 cells. A partial cDNA was isolated from rat GH3 cells which is nearly identical (99.6% nucleotide identity) to rat c-erbA alpha, except for a unique 3'-region corresponding to the carboxyl terminal region of the predicted protein sequence. This cDNA (c-erbA alpha-2), like rat c erbA alpha, hybridizes to a 2.6 kilobase (kb) mRNA which is distinct from a 6.2 kb species that hybridizes to c-erbA beta. Since nuclear T3-binding is down regulated by T3, we hypothesized that one or both c-erbA mRNAs might be regulated by T3. GH3 cells were treated with 10 nM T3 for up to 24 h, a manipulation known to decrease nuclear T3 binding by approximately 2-fold in GH cells. Both the 6.2 kb and 2.6 kb mRNA species decreased to nearly 50% of control values at 24 h. These data indicate that these two c-erbA mRNAs are regulated by T3 and suggest that the T3 effect on T3 binding-activity in GH cells may be mediated, in part, by down-regulation of c-erbA mRNA levels. PMID- 2901668 TI - Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia. A randomized, controlled clinical trial. AB - In a double-blind study, we randomly assigned 84 patients with chronic lymphocytic leukemia who were judged to be at increased risk of bacterial infection to receive intravenous immunoglobulin G (400 mg per kilogram of body weight) or a placebo every three weeks for one year. Eligible patients had hypogammaglobulinemia, a history of infection, or both. The patients receiving immunoglobulin had significantly fewer bacterial infections during the study period than those receiving placebo (23 vs. 42; P = 0.01). This reduction was most striking in the patients who completed a full year of treatment (14 vs. 36; P = 0.001). The period from study entry to the first serious bacterial infection was significantly longer in the patients receiving immunoglobulin (P = 0.026). There was no significant difference between the two groups in the incidence of nonbacterial infection. Immunoglobulin therapy was tolerated well; there were no serious adverse reactions, and the incidence of minor reactions was low. We conclude that selected patients with chronic lymphocytic leukemia who are at risk of bacterial infection can be substantially protected from this complication by the regular intravenous administration of immunoglobulin. PMID- 2901669 TI - Membrane potential has no direct role in evoking neurotransmitter release. AB - Neurons communicate by secreting a transmitter that excites or inhibits other neurons at synapses. The role of presynaptic membrane potential in triggering transmitter release is still controversial. In one view, presynaptic action potentials trigger the release by the entry of calcium ions into presynaptic terminals through voltage-dependent calcium channels. Calcium acts at high local concentrations at release sites near channel mouths to cause neurosecretion. An opposing view is that, in addition to elevating presynaptic calcium, presynaptic potential stimulates transmitter release by a distinct direct action. The relative importance of depolarization and calcium entry in neurosecretion cannot be determined because the two events are tightly linked. To delineate the roles of presynaptic potential and calcium entry in transmitter release, we have used nitr-5, a photolabile calcium chelator, and a voltage-clamp technique to control intracellular calcium and membrane potential independently at a synapse formed between cell bodies of cultured neurons of the fresh water snail Helisoma trivolvis. We found transmitter release occurred when presynaptic calcium levels were elevated to concentrations of a few micromolar, and that presynaptic voltage had no direct effect on neurosecretion. PMID- 2901670 TI - Electrogenic glutamate uptake in glial cells is activated by intracellular potassium. AB - Uptake of glutamate into glial cells in the CNS maintains the extracellular glutamate concentration below neurotoxic levels and helps terminate its action as a neurotransmitter. The co-transport of two sodium ions on the glutamate carrier is thought to provide the energy needed to transport glutamate into cells. We have shown recently that glutamate uptake can be detected electrically because the excess of Na+ ions transported with each glutamate anion results in a net current flow into the cell. We took advantage of the control of the environment, both inside and outside the cell, provided by whole-cell patch-clamping and now report that glutamate uptake is activated by intracellular potassium and inhibited by extracellular potassium. Our results indicate that one K+ ion is transported out of the cell each time a glutamate anion and three Na+ ions are transported in. A carrier with this stoichiometry can accumulate glutamate against a much greater concentration gradient than a carrier co-transporting one glutamate anion and two Na+ ions. Pathological rises in extracellular potassium concentration will inhibit glutamate uptake by depolarizing glial cells and by preventing the loss of K+ from the glutamate carrier. This will facilitate a rise in the extracellular glutamate concentration to neurotoxic levels and contribute to the neuronal death occurring in brain anoxia and ischaemia. PMID- 2901671 TI - Effects of zolantidine a brain-penetrating H2-receptor antagonist, on naloxone sensitive and naloxone-resistant analgesia. AB - The action of zolantidine, a histamine H2-receptor antagonist which penetrates the brain, was characterized on the analgesia elicited by brief continuous footshock of 3 intensities. Zolantidine inhibited the analgesia elicited by exposure to 3.5 mA for 3 min, with maximum inhibition observed 30 min after a dose of 5 mg/kg. This inhibition was not dose-related, possibly due to inhibition of the metabolism of histamine in brain by this drug at larger doses. While zolantidine alone, or in combination with naloxone, attenuated this analgesic response, naloxone alone had no such effect, further supporting the non-opiate nature of this response. Conversely, naloxone, but not zolantidine, strongly inhibited the analgesia elicited by 2.0 mA for 3 min, confirming the apparent opiate nature of this analgesic mechanism. Although a combination of zolantidine and naloxone still significantly attenuated this response, a tendency toward reversal of the antagonism by naloxone was observed with this combination of drugs, consistent with previous findings. Furthermore, the analgesia elicited by 2.5 mA for 3 min was resistant to both naloxone and zolantidine, alone or in combination. These results further strengthen the hypothesis that histamine and H2-receptors in brain are important mediators of endogenous antinociception and also support the possible existence of an additional non-opiate, non-H2-analgesic mechanism. PMID- 2901672 TI - Chronic benzodiazepine treatment increases the effects of the inverse agonist FG7142. AB - A schedule of treatment with the benzodiazepine, flurazepam, in mice for 7 days caused a significant enhancement of the convulsive effects of the partial inverse agonist FG7142. Full convulsions were seen with FG7142 after the chronic administration of flurazepam, although this compound does not cause convulsions in normal mice of the strain used. The change appeared to be maximal at 24 hr after the last dose of flurazepam and lasted for up to a week. The chronic treatment with flurazepam caused tolerance to the effects of flurazepam, but the tolerance was of shorter duration than the increase in the effects of FG7142. When the benzodiazepine antagonist, Ro 15-1788, was given with the flurazepam, the incidence of convulsions induced by FG7142 was no longer significant. Repeated administration of midazolam also slightly increased the effects of FG7142. Single doses of flurazepam or midazolam did not significantly alter the effects of FG7142, although some convulsions were seen. PMID- 2901673 TI - Concurrent monitoring of central carbamazepine and transmitter amine metabolism and motor activity in individual unrestrained rats using repetitive withdrawal of cerebrospinal fluid. AB - A method for repeated withdrawal of cerebrospinal fluid (CSF) from the cisterna magna was used in a pharmacokinetic and behavioural study of conscious, freely moving rats, given the antiepileptic drug carbamazepine (35 mg/kg i.p.). Pharmacokinetic constants (i.e. time to peak concentration, peak concentration, area under the curve and t 1/2) for the drug and its primary metabolite carbamazepine-10,11-epoxide and also concentrations of acidic metabolites of 5 hydroxytryptamine and dopamine were obtained for the CSF of individual rats. A pharmacodynamic constant, the effective concentration of drug in CSF for 50% inhibition of motor activity was also determined for each animal. The above data provides good indices of the corresponding values for carbamazepine and its metabolite in brain insofar as a separate experiment showed good correlations between CSF and brain for concentrations of both the drug and its metabolite. Carbamazepine appeared to be largely responsible for the depression of motor activity as the metabolite, at the levels attained, seemed to have little effect. The changes in motor activity were not associated with altered concentrations of the metabolites of 5-hydroxytryptamine or dopamine in the CSF. While the investigation did not reveal major advantages in monitoring the drug under study in CSF rather than in serum it illustrates the potential of the CSF method as a simple way to obtain neuropharmacokinetic and neuropharmacodynamic profiles of the action of drugs in individual rats. PMID- 2901674 TI - Evidence for a peripheral action of thyrotropin releasing hormone on gastrointestinal transit in mice. AB - The effect of the two analogs of thyrotropin-releasing hormone (TRH), namely MK 771 and DN-1417, administered peripherally, on the actions of morphine and loperamide on gastrointestinal transit, was investigated in mice. The actions of naltrexone and methyl naltrexone on these effects were also determined in order to assess the central or peripheral mechanism of action. The administration of morphine sulfate (5 mg/kg) inhibited gastrointestinal transit, as measured by the charcoal meal test. The effect of morphine was potentiated by MK-771 and DN-1417 at the 10 mg/kg dose. The peripheral administration of DN-1417 inhibited gastrointestinal transit but MK-771 had no effect. Naltrexone antagonized the potentiating effect of the peptides on the effect of morphine on gastrointestinal transit. Methyl naltrexone, which crosses the blood-brain barrier with difficulty, also antagonized the potentiating effect of the peptides on the action of morphine on gastrointestinal transit. A subthreshold dose (0.5 mg/kg) of loperamide, a peripherally acting opiate, which had no effect on gastrointestinal transit by itself, when combined with MK-771 or DN-1417 significantly inhibited gastrointestinal transit. The administration of methyl naltrexone had little effect on loperamide-induced inhibition of gastrointestinal transit but antagonized the potentiating effect of MK-771 and DN-1417. It is concluded that the effects of analogs of thyrotropin releasing hormone on gastrointestinal transit involve peripheral sites of action, the effect of DN 1417 was not antagonized by naloxone and that the inhibitory effect of DN-1417 on gastrointestinal transit is not mediated by opiate receptors. PMID- 2901675 TI - Stimulation of D-1 dopamine receptors facilitates D-2 dopamine receptor recovery after irreversible receptor blockade. AB - The hypothesis that stimulation of the D-1 dopamine receptor subtype affects the recovery of the D-2 subtype after alkylation by EEDQ was investigated. Animals were pretreated with either SCH23390, to protect D-1 receptors, or saline, before administration of EEDQ. After EEDQ one group of saline pretreated animals received 12 hourly injections of the D-1 agonist SKF38393. Animals were sacrificed at 6, 24 and 48 hours after EEDQ and Kd and Bmax of striatal D-1 and D 2 receptors measured. The concentration of D-2 receptors in the groups in which D 1 receptors had been protected by SCH23390 or stimulated by SKF38393 were significantly greater than that of the EEDQ alone group. PMID- 2901676 TI - Epileptiform activity induced by magnesium-free solution in slices of rat amygdala: antagonism by N-methyl-D-aspartate receptor antagonists. AB - The effects of the N-methyl-D-aspartate (NMDA) receptor antagonists, D-2-amino-5 phosphonovalerate (D-APV) and phencyclidine (PCP), were studied in vitro on epileptiform activity induced in magnesium-free solution in neurons of the basolateral amygdala of the rat, using intracellular recording techniques. Twenty to 30 min after switching to magnesium-free medium, spontaneous interictal-like events were observed in 33 out of 37 amygdala slices. The spontaneous interictal like events consisted of an initial burst followed by a number of afterdischarges. Superfusion with D-APV, a competitive NMDA receptor antagonist, reversibly reduced the duration of the events was also reduced. The IC50, estimated from the graph of the concentration-response relationship, was approximately 10 microM which is close to the IC50 for the binding of D-AVP to the NMDA receptor in other regions of the brain. The effect of phencyclidine, a noncompetitive NMDA receptor antagonist, was similar to that of D-APV. These results suggest that activation of NMDA receptors plays an intrinsic role in the induction or propagation of epileptiform activity seen in magnesium-free solution in the neurons of the amygdala. PMID- 2901678 TI - Learning impairment in rats by N-methyl-D-aspartate receptor antagonists. AB - 2-Amino-5-phosphonovalerate (APV, icv) phencyclidine (PCP, ip) and scopolamine (sc) dose-dependently disrupted short term working memory in radial maze. These drugs injected before, but not after training attenuated retention of long term memory in passive avoidance task. A relation of PCP action to its antagonism at NMDA receptors may be suggested. PMID- 2901677 TI - The importance of dopaminergic neurotransmission in the hypermotility response produced by the administration of N-methyl-D-aspartic acid into the nucleus accumbens. AB - The bilateral injection of N-methyl-D-aspartic acid (NMA) into the nucleus accumbens of rats has been shown to stimulate locomotor activity. This response is antagonized by drugs that interfere with dopaminergic neurotransmission, such as reserpine, alpha-methyl-p-tyrosine (AMPT) and haloperidol, suggesting that NMA may exert its effects by stimulating the release of dopamine (DA) from nerve terminals. To test this hypothesis, the ability of NMA to release endogenous DA from slices of nucleus accumbens, which were incubated in magnesium-free medium was evaluated. It was found that NMA, at concentrations of 0.1 and 1 mM, did not stimulate the release of endogenous DA from slices in magnesium-free normal medium, medium containing pargyline (to inhibit monoamine oxidase) or medium containing methylphenidate (to block the reuptake of released DA). In contrast, both amphetamine (10(-5) M) and a high potassium (20 and 40 mM) stimulated the release of endogenous dopamine. The lack of effect of NMA on the release of endogenous DA was supported by in vivo studies which showed that the injection of NMA into the nucleus accumbens, in a dose that stimulated locomotor activity, did not increase the turnover of dopamine as reflected by an increase in the concentration of DOPAC. In contrast, the direct administration of haloperidol (13 nmol) into the nucleus accumbens produced a marked increase in the concentration of DOPAC. To determine the role of activation of DA receptors in the hypermotility response to NMA, NMA was administered together with subthreshold doses of either DA or apomorphine into the nucleus accumbens of rats pretreated with AMPT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901679 TI - The pharmacology of excitatory transmission in the rat olfactory cortex slice. AB - The pharmacology of excitatory transmission in slices of olfactory cortex of the rat, perfused with solution containing picrotoxin, has been studied by assessing the effects of cis-2,3-piperidine dicarboxylate, a nonselective antagonist of excitatory amino acid receptors, 2-amino-5-phosphonopentanoate, a selective antagonist of N-methyl-D-aspartate (NMDA) receptors and 2-amino-4 phosphonobutyrate (APB) and baclofen, which act at APB and GABAB sites, respectively, on evoked surface field potentials. Monosynaptic excitatory transmission was monitored by measuring the amplitude of the N'a'-wave, evoked on stimulation of the lateral olfactory tract, whilst di-/polysynaptic excitatory transmission was evaluated by calculating the areas of the potentials evoked on direct stimulation of the superficial and deep-lying association fibre systems. On the basis of the effects of the drugs in this and earlier studies, it is concluded that: (i) transmission at the lateral olfactory tract-pyramidal cell synapse is mediated by kainate/quisqualate but not NMDA receptors and is regulated by inhibitory APB receptors, located on the tract terminals; (ii) NMDA receptors are involved in mediating excitatory transmission at the synapses of superficial association fibres with the proximal apical dendrites of pyramidal cells with inhibitory APB receptors playing a regulatory role; (iii) transmission at synapses of association fibres with basal dendrites of pyramidal cells, is mediated in part by NMDA receptors with (presynaptic?) GABAB receptors exerting a strong inhibitory influence. These proposed roles of NMDA receptors have been confirmed in experiments in which the effects of magnesium ions on field potentials evoked in slices perfused in magnesium-free solution were monitored. PMID- 2901680 TI - Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B agonists: a comparative study with dorsal raphe neurons. AB - In low cerveau isole transected rats, the effects of microiontophoretic application of putative serotonin 5-HT1A and 5-HT1B agonists on the spontaneous firing rate of CA1 pyramidal cells were compared to those of 5-HT. In contrast to the large current-dependent suppression of unit activity observed with 5-HT, the 5-HT1A compounds, ipsapirone, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)-tetralin) and LY 165163 (p-aminophenylethyl-m-trifluoromethylphenylpiperazine) and the 5 HT1B compounds, mCPP (m-chlorophenylpiperazine) and TFMPP (trifluoromethylphenylpiperazine), produced only weak inhibition of spontaneous firing. Conversely, using identical ejection parameters, ipsapirone and LY 165163 (previously reported) and 8-OH-DPAT were as effective as 5-HT in inhibiting markedly the baseline activity of serotonergic dorsal raphe neurons; mCPP and TFMPP (previously reported) were only weakly active. In view of the minor suppressant effects of the 5-HT1A agonists on the firing of pyramidal cells, a modulatory role for these compounds was sought. Excitation of pyrimadal cells, induced by microiontophoretic application of glutamate, was attenuated by ipsapirone and 8-OH-DPAT; however, when directly compared in the same cells, ipsapirone was no more effective than the 5-HT1B agonist, mCPP. In summary, the inability of CA1 pyramidal cells to distinguish the actions of 5-HT1A and 5-HT1B ligands is in sharp contrast to the striking differences observed for these compounds with dorsal raphe neurons. Consistent with these findings is the idea that 5-HT1A compounds are full agonists on dorsal raphe neurons but only partial agonists on pyramidal cells. PMID- 2901681 TI - Depletion of monoamine transmitters by tetrabenazine in brain tissue in Huntington's disease. AB - The neurochemical effect of tetrabenazine was assessed by determining the levels of dopamine, noradrenaline and 5-hydroxytryptamine and their metabolites in post mortem brain from Huntington's disease patients with or without a history of tetrabenazine treatment. The tetrabenazine-treated group showed a general description of monoamines in all regions studied, the greatest reduction being dopamine in the caudate. This provides the basis for the effect of tetrabenzine on chorea, while monoamine losses in limbic regions may mediate the production of side effects, such as depression. PMID- 2901682 TI - Pharmacological characteristics of the postsynaptically mediated contractile responses of guinea-pig ileum to long-lasting electrical field stimulation. AB - The contractile responses of the longitudinal smooth muscle layer of the isolated guinea-pig ileum which were elicited by long-lasting (40 sec train duration) electrical field stimulation (0.8 msec, 20 V), applied at a frequency of either 5 or 30 Hz, comprised an initial phasic component followed by a secondary tonic contraction, were studied against the background of postsynaptically-acting receptor antagonists. Atropine and apamin reduced both components of the responses while prazosin produced no change. Propranolol induced a slight reduction, decreasing mainly the responses evoked by stimulation at a frequency of 5 Hz. The simultaneous application of cholinoceptor and adrenoceptor blockers revealed a non-cholinergic, non-adrenergic component of the responses. The putative prostaglandin antagonist, SC 19220 was found to reduce mainly the tonic component of the non-cholinergic, non-adrenergic contractions evoked by stimulation at both frequencies used. These results demonstrated that the two component contractile responses of the guinea pig ileum to long-lasting electrical stimulation were due to the release of more than one neurotransmitter and/or spasmogenic substance. It is concluded that the initial phasic component was evoked by acetylcholine and by a non-cholinergic, non-adrenergic neurotransmitter, while the tonic component was maintained predominantly by prostaglandins released during stimulation. PMID- 2901683 TI - Changes in neurotransmitter release at a neuromuscular junction of the lobster caused by cannabinoids. AB - In vitro intracellular recording techniques were used on an excitatory neuromuscular junction of a walking-limb stretcher muscle of the lobster in order to define the synaptic pharmacology of delta-9-tetrahydrocannabinol (THC), 11 hydroxy-THC and cannabidiol. Delta-9-tetrahydrocannabinol and 11-hydroxy-THC, in relatively small concentrations, increased the amplitude of the excitatory junctional potential and the mean quantum content of a muscle fiber, whereas larger concentrations produced depression. In contrast, cannabidiol reduced the excitatory junctional potential and the mean quantum content. All three cannabinoids, however, depressed the amplitude of the spontaneous miniature junctional potential. The changes in mean quantum content point to a presynaptic site of action for the drug, while the reduction of the amplitude of the miniature junctional potential presumes a postsynaptic site. Such findings suggest synaptic mechanisms and sites of action for the central excitatory and depressant properties of the cannabinoids. PMID- 2901684 TI - Dynorphin (1-8) inhibits stimulated release of oxytocin but not vasopressin from isolated neurosecretory endings of the rat neurohypophysis. AB - The effects of the opioid peptide dynorphin (1-8) on oxytocin and vasopressin release at the level of isolated neurosecretory endings were investigated. Neurosecretory endings prepared by homogenization and centrifugation were placed on a filter and constantly superfused. Stimulated hormone release was evoked by potassium depolarization (30 mM) and simultaneous increase of the osmolarity (20 mosmol/1). Stimulation resulted in two peaks of hormone release--a short first peak and a longer second one. Addition of dynorphin (1-8) (10(-7) M) to the superfusion buffer significantly diminished the first peak of oxytocin release and totally abolished the second. There was no effect of dynorphin (1-8) on vasopressin release. PMID- 2901685 TI - The ionic mechanisms underlying opioid actions. AB - Recent experiments using intracellular recording techniques in vitro have revealed that common ionic mechanisms may explain the actions of opioid drugs. Evidence is now available from studies on guinea pig gut myenteric and submucous plexi, from preparations of spinal cord and dorsal root ganglia, from brain slices including the locus coeruleus and from neuroblastoma/glioma hybrid cells. The concensus is that mu opioid receptors activate an outward potassium conductance, possibly by way of adenylate cyclase. Activation of the receptor increases the membrane permeability to potassium ions and thus produces a membrane hyperpolarisation and conductance increase, plus an indirect inhibition of calcium entry during the action potential. Kappa opioids appear to inhibit directly the entry of calcium through voltage-dependent calcium channels, although to date there is no conclusive evidence that this mechanism of action can be extended to neurones of the central nervous system. The mechanism of action of delta opioids has only recently been investigated and initial evidence suggests they increase a potassium conductance similar to that increased by mu opioids. However, work in neuroblastoma x glioma hybrid cells has suggested that in these cells at least, receptor activation depress a component of voltage dependent calcium current. The link between the receptor and the calcium channel involves a G-protein, Go. PMID- 2901686 TI - Measurement of dynorphins with 3H-etorphine and canine limbic system receptors. AB - A canine limbic system preparation was used as the source of opioid peptide receptors to screen biologic extracts for the presence of opioid receptoractive peptides following their gradient RP-HPLC separation. Eight synthetic dynorphin peptides were studied for their ability to displace the commonly-used ligand 3H etorphine from the canine limbic system P2 preparation. The peptides studied included the dynorphins 1-7, 1-8, 1-9, 1-10, 1-12, 1-13, 1-17, and dynorphin B. Two different types of opioid peptide molecules were utilized for the determination of the level of non-specific binding. In one study, methionine enkephalin, and in the second study each one of the eight corresponding dynorphins, was used for determination of non-specific binding. The experimental data indicated that 3H-etorphine bound to the canine limbic system P2 receptors, and that those dynorphins displaced effectively the 3H-etorphine from those receptors. PMID- 2901687 TI - Occurrence of pyroglutamyl peptidase II, a specific TRH degrading enzyme in rabbit retinal membranes and in human retinoblastoma cells. AB - Pyroglutamyl peptidase II, a highly specific thyrotropin releasing hormone (TRH) degrading enzyme is found in highest concentration in brain where it is localized to synaptic membranes. Retina contains relatively high concentrations of both immunoreactive TRH and TRH receptors. We report that the specific activity of pyroglutamyl peptidase II in rabbit retinal membranes exceeds that of all non-CNS tissues thus far studied. Nine clonal cell lines were screened for this enzymatic activity. The specific activity of pyroglutamyl peptidase II in Y79 retinoblastoma cells was greater than the highest activity found in other cell lines by approximately one order of magnitude. These studies further support a functional relationship between pyroglutamyl peptidase II and TRH and identify a cell line suitable for studies on the regulation of this enzyme. PMID- 2901688 TI - Effects of neuronotrophic factors on adrenal medulla grafts implanted into adult rat brains. AB - The effects of neuronotrophic factors (NFs) on adult adrenal medulla grafts transplanted into the rat caudate nucleus after the destruction of the nigrostriatal dopaminergic pathways were investigated. Two months after implantation, all of the adrenal medulla grafts treated with NFs, but only 45% of the untreated grafts, had survived. The levels of tyrosine hydroxylase activity in the caudate nucleus however, were not significantly different between the sham operated control and either NF-treated or untreated grafted groups. These results indicate that treatment with NFs significantly enhances the survival rate of the grafts. PMID- 2901689 TI - [3H]D-2-amino-5-phosphonopentanoate as a ligand for N-methyl-D-aspartate receptors in the mammalian central nervous system. AB - Tritiated D-2-amino-5-phosphonopentanoate has been prepared and evaluated as a radioligand for investigating N-methyl-D-aspartate receptors in rat brain membranes. A radioactive impurity, which was more acidic than 2-amino-5 phosphonopentanoate, interfered with the binding assay for [3H]D-2-amino-5 phosphonopentanoate in preliminary experiments and developed progressively with time of storage of the ligand, was isolated by ion-exchange purification and its binding site characterized. Binding of the 3H-impurity was increased in the presence of calcium ions, with a maximum effect at a concentration of 1-3 mM, but not by sodium, potassium or magnesium ions. It was inhibited by omega-phosphonate analogues of D-2-amino-5-phosphonopentanoate and by inorganic phosphate but not by L-glutamate or any other omega-carboxylates, omega-sulphinates or omega sulphonates tested. The site of binding for the 3H-impurity was not identified, but from its pharmacological profile it appears to be unrelated to any excitatory amino acid receptor so far described. Binding of purified [3H]D-2-amino-5 phosphonopentanoate to rat cerebral cortical membranes was saturable (KD, 0.53 microM; Bmax, 4.3 pmol/mg protein), was maximal at pH 7.3, but was not particularly temperature sensitive. Dissociation of the receptor-ligand complex was very rapid. Magnesium ions had an inhibitory effect on the binding of [3H]D-2 amino-5-phosphonopentanoate, but the mechanism of this action was not clear. For a wide range of competitive excitatory amino acid antagonists with different potencies and receptor specificities there was a direct relationship between their Ki values as inhibitors of [3H]D-2-amino-5-phosphonopentanoate binding and their KD values for antagonism of N-methyl-D-aspartate induced depolarizations. Thus, [3H]D-2-amino-5-phosphonopentanoate binds to electrophysiological N-methyl D-aspartate receptors. Among endogenous agonists, L-glutamate had the highest affinity (Ki 0.9 microM) for the [3H]D-2-amino-5-phosphonopentanoate binding site; L-homocysteate and S-sulpho-L-cysteine also had high affinity. However, quinolinate and N-acetylaspartylglutamate had relatively low affinity. It is considered that L-glutamate is the most likely substance to be the transmitter activating N-methyl-D-aspartate receptors physiologically. A study of the regional distribution of [3H]D-2-amino-5-phosphonopentanoate binding sites showed the hippocampus and cerebral cortex to have the highest density of these sites, while the cerebellum and spinal cord had the lowest.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2901690 TI - [3H]SCH 23390 binding to D1 dopamine receptors in the basal ganglia of the cat and primate: delineation of striosomal compartments and pallidal and nigral subdivisions. AB - The distribution of D1 dopamine receptors was studied autoradiographically in the basal ganglia of the cat, monkey and human. These receptor binding sites were labeled directly with the D1-selective antagonist [3H]SCH 23390, and ligand binding assays were performed concurrently. Serial- or same-action analysis permitted comparisons among D1 binding distributions, acetylcholinesterase staining and tyrosine hydroxylase immunoreactivity. In all species studied, the dorsal striatum exhibited patches of particularly dense D1 binding in correspondence with acetylcholinesterase-poor striosomes. Highly patterned binding was present in the ventral striatum. Distinctions in binding density were observed among the subdivisions of the globus pallidus and of the substantia nigra. The external segment of the pallidum was extremely sparse in D1 binding, whereas the internal segment (or entopeduncular nucleus in the cat) was a site of high D1 binding density. The binding density was greatest in the core of the internal segment, and tyrosine hydroxylase-positive fibers surrounded and weakly dispersed themselves through this core. Weak binding was present in the ventral pallidum. In the substantia nigra, the pars reticulata demonstrated the densest binding, particularly medially. The pars compacta showed much sparser binding, though some of its tyrosine hydroxylase-positive neurons had dendrites extending ventrally into the zone of dense D1 binding in the pars reticulata. We conclude that [3H]SCH 23390-defined D1 binding is compartmentalized in the dorsal striatum and that, particularly in relation to the reported distributions of striatal D2 dopamine receptors, this is likely to be of functional significance in the dopaminergic modulation of intrastriatal neurotransmission as well as of afferent and efferent neurotransmission. The segregated localizations of D1 receptors in the substantia nigra suggest predominant activation of the pars reticulata, including ventral and medial regions adjacent to the densocellular zone. Specific pathways from compartments in the striatum to subdivisions of the pallidum may also be differentially modulated by dopamine acting via distinct receptor subtypes. At the level of the pallidum, such D1 modulation appears to be restricted to the internal segment, which projects to the thalamus, rather than to the external pallidum, which projects to the subthalamic nucleus. PMID- 2901691 TI - Structure/activity relations of N-methyl-D-aspartate receptor ligands as studied by their inhibition of [3H]D-2-amino-5-phosphonopentanoic acid binding in rat brain membranes. AB - Structure/activity relations of agonists and antagonists for the N-methyl-D aspartate receptor have been investigated by measuring the ability of a large range of substances to inhibit binding of [3H]2-amino-5-phosphonopentanoate to rat brain membranes. A major difference between optimum structures for agonist and antagonist activity lay in the differential effectiveness of sulphonic and phosphonic acid groups as the omega-acidic terminal in these two types of compound. The sulphonic acid moiety was an effective omega-acidic terminal in short chain agonists, but not in longer chain antagonists, while the phosphonic acid group was the most effective omega-acidic terminal in longer chain antagonists, but was only very weakly active in short chain agonists. It is proposed that the binding site of the omega-acidic terminal of antagonists is different from that for the omega-acidic group of agonists. Other structural features conducive to effective interaction of ligands with the receptor are discussed. PMID- 2901692 TI - The distribution of neuropeptide Y-like immunoreactive neurons in the human medulla oblongata. AB - We have described the distribution of neuropeptide Y-like immunoreactive neurons in the medulla oblongata of the adult human. The majority of neuropeptide Y-like immunoreactive cells were found in four regions of the medulla: the ventrolateral reticular formation, the dorsomedial medulla, the secondary sensory nuclei and the rostral raphe nuclei. The morphology of neuropeptide Y-like immunoreactive cells varied in each of these regions. In the ventrolateral reticular formation, the labelled neurons were round and pigmented caudal to the obex but elongated and non-pigmented rostral to the obex; in the dorsomedial medulla, they were triangular and pigmented caudal to but not rostral to the obex; in the secondary sensory nuclei, they were multipolar, non-pigmented and significantly smaller than in the other areas; in the rostral raphe nuclei, they were bipolar and non pigmented. Colocalization studies revealed that many neuropeptide Y-like immunoreactive cells also synthesize monoamines, consistent with conclusions based on a quantitative comparison of their distributions. Neuropeptide Y-like immunoreactivity was present in about 25% of presumed noradrenaline-synthesizing cells in the caudal ventrolateral medulla (corresponding to the A1 region); about 50% of adrenaline- and 70% of presumed serotonin-synthesizing cells in the rostral ventrolateral medulla (C1 and B2-3 regions); 90-100% of presumed noradrenaline-synthesizing cells in the dorsomedial medulla at and above the obex (A2 region); about 50% of adrenaline-synthesizing cells in the rostral dorsomedial medulla (C2 region); about 5% of presumed serotonin-synthesizing cells in the rostral raphe nuclei (B2-3 region). The largest of these groups was the presumed serotonin-synthesizing cells that contained neuropeptide Y-like immunoreactivity in the rostral ventrolateral medulla. This is the first report of such a cell group in the medulla of any mammal, and emphasizes the neuroanatomical differences between humans and other species. PMID- 2901693 TI - Glucose deprivation depolarizes plasma membrane of cultured astrocytes and collapses transmembrane potassium and glutamate gradients. AB - Primary cultures of astrocytes were used to investigate the effects of glucose deprivation on plasma membrane potential, on the respiration and on the energy status of these cells. Plasma membrane potential, as monitored with a cyanine dye, 3,3'-diethylthiadicarbocyanine, hyperpolarized by about 100% when glucose was added to substrate-deprived cells. The effect of glucose was prevented by iodoacetate or ouabain. In the absence of glucose, cellular adenosine triphosphate/adenosine diphosphate ratio was extensively reduced and pyruvate was unable either to restore energy status or to hyperpolarize the plasma membrane of astrocytes, although it was the preferential substrate for mitochondria within the cells. Glucose deprivation and inhibition of glycolysis or respiration in the presence of glucose caused dramatic decrease in transmembrane potassium ion and L glutamate gradients. The gradients were not restored in the presence of pyruvate. Thus, aerobic glycolysis, rather than oxidation of pyruvate, is required to maintain maximal plasma membrane potential, adenosine triphosphate/adenosine diphosphate ratios as well as K+ and L-glutamate gradients. This evidence, together with the unresponsiveness of astrocyte respiration to ouabain, indicates a functional dissociation between energy dissipation at the plasma membrane and mitochondrial synthesis of adenosine triphosphate. The results are discussed with regard to the vulnerability of glia at low levels of blood glucose and the contribution of glial dysfunction to development of hypoglycaemic encephalopathy. PMID- 2901694 TI - Cyclic GMP and cell death in rat cerebellar slices. AB - Incubated slices of young rat cerebellum were used to examine the possible relationship between the neurotoxic effects of excitatory amino acids and their ability to elicit large increases in the levels of cyclic GMP in this tissue. No cell death was detectable following exposure of the slices to the guanylate cyclase activator, nitroprusside (up to 0.3 mM), the phosphodiesterase inhibitor, isobutylmethylxanthine (0.5 mM), or to cyclic GMP (10 mM) and its dibutyryl and 8 bromo derivatives (0.5 mM). However, incubation of the slices with tbe guanylate cyclase inhibitors, N-methylhydroxylamine and hydroxylamine (0.1-1 mM), methylene blue (10-100 microM), ethacrynic acid (300 microM) and retinol (1 mM) caused a progressive destruction of the differentiating cells. The damage induced by N methylhydroxylamine and hydroxylamine was inhibited by nitroprusside, cyclic GMP and isobutylmethylxanthine. It could also be reduced by lowering the partial pressure of oxygen, by oxygen radical scavenging enzymes and by omitting Ca2+ from the medium. Oxygen radical generating enzyme systems mimicked the pattern of toxicity of the guanylate cyclase inhibitors but their effects were not reduced by nitroprusside or omission of Ca2+. The results indicate that guanylate cyclase/cyclic GMP does not mediate amino acid neurotoxicity but, instead, may be part of a protective mechanism against oxygen free radicals. PMID- 2901695 TI - Antibodies against GABA and glutamate label neurons with morphologically distinct synaptic vesicles in the locust central nervous system. AB - Antibodies raised against GABA and glutamate were used to stain sections through locust thoracic ganglia for light and electron microscopy. Using a peroxidase antiperoxidase method for light microscopy, the GABA antibody was shown to label inhibitory motor neurons thought to use GABA as their neurotransmitter, and the glutamate antibody to label excitatory motor neurons thought to use glutamate. An immunogold method was used to reveal labelled neuropilar processes in the electron microscope. Each antibody specifically labels a particular population of processes. With the GABA antibody, labelling is equally clear whether the processes concerned contain synaptic vesicles or not and is strongly contrasted against very low background levels. With the glutamate antibody, most processes show some affinity for the antibody, probably reflecting the presence of metabolic glutamate, however one population can be clearly distinguished by the presence of a much greater density of gold particles over synaptic vesicles. In the locust it appears, therefore, that the antibody can distinguish clearly between the metabolic and neurotransmitter pools of glutamate. It has been proposed that synaptic vesicles in GABAergic neurons have a different shape to those in glutamatergic neurons. This was supported by the electron microscope immunocytochemistry. Those showing GABA-like immunoreactivity contain predominantly pleomorphic agranular vesicles approximately 21 x 30 nm in diameter. Those showing glutamate-like immunoreactivity contain round agranular vesicles of about 38 nm in diameter. The GABA antibody appears to label all processes containing pleomorphic agranular vesicles. By contrast, some processes containing round agranular vesicles are not labelled by the glutamate antibody, even though the vesicles they contain are statistically identical in size to those in labelled profiles. With neither antibody was the labelling of glial cells greater than the background level. PMID- 2901696 TI - CNS amyloid proteins in neurodegenerative diseases. AB - The amyloid plaques found in neurodegenerative diseases show considerable morphologic diversity. Two amyloidogenic proteins have been isolated from the brains of humans and animals with neurodegenerative diseases--beta-protein from Alzheimer's disease (AD) and Down's syndrome, and prion protein (PrP) from scrapie and Creutzfeldt-Jakob disease (CJD). Using monoclonal antibodies to a synthetic peptide corresponding to a portion of beta-protein and rabbit antiserum to hamster scrapie PrP 27-30, we examined in situ amyloid plaques on sections from cases of neurodegenerative diseases, including cases with a spectrum of plaque types. Anti-beta-peptide stained cerebrovascular and plaque core amyloid in all AD cases as well as cerebrovascular amyloid and senile plaque core amyloid in five elderly CJD cases. Anti-PrP stained plaques in CJD, kuru, and Gerstmann Straussler syndrome cases but not cerebrovascular amyloid or plaques in AD. Dual localization experiments showed that in cases with a mixture of plaque types, the antibodies identified different populations of plaques that showed anatomic heterogeneity. Colocalization of the two proteins was not observed in any plaque type. The data suggest that in neurodegenerative diseases two major plaque types exist, which have different etiologic origins. Our results emphasize the need for classification of CNS amyloids based not on their morphology but on the macromolecular components comprising these pathologic polymers. PMID- 2901697 TI - PHNO [(+)-4-propyl-9-hydroxynaphthoxazine]: a new and effective anti-Parkinson's disease agent. AB - PHNO [(+)-4-propyl-9-hydroxynaphthoxazine] is a chemically novel and highly potent dopamine (D2) receptor agonist without D1 activity. It had significant antiparkinsonism effects when used as open-label monotherapy in ten patients who were Hoehn and Yahr stage 2 or 3. The standard formulation of PHNO produced a 3- to 4-hour therapeutic effect in most patients; the response to the time-release formulation lasted up to 10 hours. Side effects were similar to those of other dopamine agonists but dyskinesia was seen in only one patient. PMID- 2901698 TI - Elevated serum antibody titers to Epstein-Barr virus in HTLV-I-associated myelopathy (HAM). AB - We studied the serum antibody titers to Epstein-Barr virus (EBV) in 11 patients with HTLV-I-associated myelopathy (HAM). HAM patients showed significant increases in IgG antibodies to EBV-capsid antigen (VCA) and -early antigen (EA) and in VCA-specific IgA compared with 25 seronegative subjects. However, there were no significant differences in antibodies to EBV-nuclear antigen (EBNA) or to other viruses between the two groups. In HAM patients, altered antibody responses occurred specifically to EBV-associated antigens, not to other viruses. PMID- 2901699 TI - A population of very small striatal neurons in the cat displays vasoactive intestinal polypeptide immunoreactivity. AB - Cells displaying vasoactive intestinal polypeptide (VIP) immunoreactivity were demonstrated in the feline striatum using a monoclonal antibody raised against natural porcine VIP. The VIP-immunoreactive neurons in the cat striatum were very small, (8 microns diameter) bipolar and multipolar cells. The VIP-positive neurons were more numerous than the cholinergic neurons but less common than the somatostatin-immunoreactive cells in the cat caudate-putamen. The VIP immunoreactive cells were localized predominantly in the striatal matrix and tended to avoid enkephalin-immunoreactive patches. Thus VIP-immunoreactive cells comprise another neurochemically defined neuronal population which appears to observe striosomal organization. PMID- 2901701 TI - Low-magnesium epilepsy in rat hippocampal slices: inhibitory postsynaptic potentials in the CA1 subfield. AB - Spontaneous, synchronous epileptiform discharges were recorded in both CA3 and CA1 subfields of rat hippocampal slices perfused with Mg2+-free medium. Surgical separation of the two areas abolished the spontaneous discharges only in the CA1 subfield. However, epileptiform responses in the isolated CA1 subfield could still be evoked by orthodromic stimulation. Intracellularly these stimulus induced responses were characterized by a depolarization associated with a burst of action potentials. Stimulation of the alveus still evoked a hyperpolarizing potential, presumably a recurrent inhibitory postsynaptic potential (IPSP) in CA1 pyramidal cells. Both spontaneous and stimulus-induced epileptiform discharges were blocked by the selective antagonist of N-methyl-D-aspartate (NMDA) receptors DL-2-amino-phosphonovalerate (APV). APV also reduced the amplitude and duration of the IPSP induced by alveus stimulation. Thus, epileptiform discharges evoked by lowering Mg2+ in the CA1 subfield are associated with a preservation of inhibitory mechanisms. Furthermore the effects exerted by APV upon the IPSP implicate that NMDA receptors might be involved in the neuronal circuit responsible for the hyperpolarizing IPSP generated by CA1 pyramidal neurons. PMID- 2901700 TI - An intracellular analysis of amino acid induced excitations of deep dorsal horn neurones in the rat spinal cord slice. AB - The rat spinal cord slice preparation has been used to investigate the sensitivity of deep dorsal horn neurones to the excitatory amino acids N-methyl-D aspartate (NMDA), quisqualate and L-glutamate. Intracellular recordings were made from 44 neurones in laminae III-VI of 14- to 16-day rats. Superfusion of quisqualate (30 microM) excited all neurones, NMDA (50 microM) excited 72% and L glutamate (0.5-1 mM) 63% of the neurones. Depolarizations were retained after tetrodotoxin but with a reduced amplitude. The NMDA antagonist D aminophosphonovalerate (D-APV, 10 microM) reduced NMDA and L-glutamate depolarizations by 66% and by 40%, respectively, while the quisqualate responses were enhanced by 27%. Dorsal root stimulation elicited two main patterns of activity; short-latency single/double spikes followed by subthreshold excitatory postsynaptic potentials (EPSPs) or a burst of spikes rising from a long duration composite EPSP. D-APV reduced the long-latency components of the first type and reduced the amplitude and duration of the composite EPSP of the second. These results support a specialized role for NMDA receptors in synaptic transmission in the dorsal horn. PMID- 2901702 TI - Dopamine release in the nucleus accumbens of freely moving rats determined by on line dialysis: effects of apomorphine and the neuroleptic-like peptide desenkephalin-gamma-endorphin. AB - This study examined the effects of apomorphine, sulpiride, desenkephalin-gamma endorphin (DE gamma E) and a combination of DE gamma E with apomorphine on the release of dopamine (DA) and its main metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens of freely moving rats. A fully automated on-line brain dialysis system was used. A small dose of s.c. administered apomorphine induced a decrease in the output of DA and DOPAC. Sulpiride, infused into the nucleus accumbens, induced a 2-fold increase in the output of DA, DOPAC and HVA. DE gamma E hardly modified either the basal release of DA, DOPAC and HVA or the apomorphine-induced attenuation of the release of DA and DOPAC. These results indicate a dissociation between the behavioural effects of DE gamma E and its effect on the release of DA in vivo. PMID- 2901703 TI - Pertussis toxin blocks the effects of alpha 2-agonists and antagonists on locus coeruleus activity in vivo. AB - This study assessed the effects of pertussis toxin, which is known to inactivate G proteins and therefore to block receptors linked to G proteins, on electrophysiological activity of the locus coeruleus in vivo. Pertussis toxin was injected into the lateral cerebral ventricle of rats, and locus coeruleus activity was then recorded. Compared to vehicle-injected control animals, pretreatment with pertussis toxin markedly increased the spontaneous firing rate of locus coeruleus neurons. In addition, the alpha 2-antagonist idazoxan was no longer able to augment either spontaneous or evoked locus coeruleus activity after pretreatment with pertussis toxin. Finally, pretreatment with pertussis toxin made locus coeruleus neurons resistant to inhibition by the alpha 2-agonist clonidine. These results are consistent with the view that pertussis toxin blocks alpha 2-receptors, receptors linked to G proteins, in vivo. PMID- 2901704 TI - Glutamine-induced membrane currents in cultured chick spinal cord neurons. AB - The effects of L-glutamine (GLN) on cultured spinal cord neurons from the chick were studied in the whole cell mode of the patch clamp technique. GLN induced membrane currents rectified at positive membrane potentials (m.p.) and reversed polarity close to zero m.p. The dose-response curve was nearly linear at a semilogarithmic scale for concentrations of 10(-5) M-10(-2) M. Summation of the responses evoked by GLN (10(-3) M) and glycine (10(-3) M) was observed when these two amino acids were applied together, while no significant increase of the responses was present when GLN was applied together with L-glutamate (10(-3) M) or kainate (10(-3) M). It is suggested that GLN binds to the glutamate receptors and activates the same type of ionic channels as glutamate and kainate. PMID- 2901705 TI - Haemophilia carrier detection using DNA analysis. PMID- 2901706 TI - [Our journal--its tasks during perestroika in the light of the resolutions of the 27th Congress of the CPSU]. PMID- 2901707 TI - Glutamate activation of neurons within trigeminal nucleus caudalis increases adrenocorticotropin in the cat. AB - The role of trigeminal nucleus caudalis (Vc) in control of the autonomic and endocrine correlates of nociception was assessed in chloralose-anesthetized cats. Microinjections of the neuroexcitatory agent, L-glutamate (0.5 M), were directed at the marginal layers, at the central magnocellular portion, and at the deep magnocellular portion of Vc. Changes in the plasma concentration of adrenocorticotropin (ACTH), in mean arterial pressure, and in heart rate were examined. Glutamate excitation of neurons within the marginal layers of Vc evoked a significant (+143 +/- 52 pg/ml, P less than 0.01) increase in plasma ACTH during the 10 min postinjection sampling period. Glutamate injections into the deep magnocellular portion of Vc also increased plasma ACTH (+97 +/- 28 pg/ml, P less than 0.05), whereas activation of neurons in the central magnocellular portion of Vc had no consistent effect on plasma ACTH (-25 +/- 29 pg/ml, P greater than 0.10). Arterial pressure increased transiently after glutamate injections into the marginal layers or central magnocellular portion of Vc, whereas injections into the deep magnocellular portion of Vc did not affect arterial pressure. Heart rate increased transiently regardless of the laminar site of injection within Vc. These data indicate that activation of neurons in laminar regions of Vc that process nociceptive information cause an increase in plasma ACTH, whereas activation of neurons in laminae of Vc that process mainly non-nociceptive input have no significant influence on plasma ACTH. PMID- 2901708 TI - Effects of a drug that blocks the vascular beta 2-receptors on blood prostanoid levels during physical exercise. PMID- 2901709 TI - [Mosquito net barriers for sample collection of zoophilic Culicidae]. AB - Mosquito net fences 2.30-2.50 m high placed around cowsheds at their night resting sites have been successfully utilized to obtain large samples of malaria vectors of the Anopheles gambiae complex and of other mosquito species. Collections of blood-fed mosquitoes were carried out during the night by inspecting regularly the net side facing the animal enclosure. This sampling procedure has important advantages over alternative procedures based on direct collection on animal or on the use of animal-baited traps. PMID- 2901710 TI - Photobinding of some 7-chloro-1,4-benzodiazepines to human plasma protein in vitro and photopharmacology of diazepam in the rat. AB - The extent to which diazepam, diazepam-N4-oxide and N4-desoxychlordiazepoxide irreversibly bind to plasma protein upon UV irradiation was determined. Comparison with the results for chlordiazepoxide leads to the conclusion that the N4-oxide function is essential for the occurrence of irreversible binding in vitro. Investigation of the photopharmacology of diazepam in the rat gave results similar to those for N4-desoxychlordiazepoxide: in contrast with what already had been found for chlordiazepoxide no difference was observed between the pharmacology of diazepam in UV-A irradiated rats and those kept in the dark. Both in vitro and in vivo data expand the hypothesis to other 7-chloro-1,4 benzodiazepines, according to which the presence of an N4-oxide group is a prerequisite for the occurrence of phototoxicity and that an oxaziridine is the toxic intermediate. PMID- 2901711 TI - Methylated DNA-binding protein is present in various mammalian cell types. AB - A DNA-binding protein from human placenta, methylated DNA-binding protein (MDBP), binds to certain DNA sequences only when they contain 5-methylcytosine (m5C) residues at specific positions. We found a very similar DNA-binding activity in nuclear extracts of rat tissues, calf thymus, human embryonal carcinoma cells, HeLa cells, and mouse LTK cells. Like human placental MDBP, the analogous DNA binding proteins from the above mammalian cell lines formed a number of different low-electrophoretic-mobility complexes with a 14-bp MDBP-specific oligonucleotide duplex. All of these complexes exhibited the same DNA methylation specificity and DNA sequence specificity. From the extracts of rat and calf tissues, oligonucleotide protein complexes formed that also had the same specificity as human placental MDBP although they had a higher electrophoretic mobility probably due to digestion by proteases in the nuclear extracts. Although MDBP activity was found in various mammalian cell types, it was not detected in extracts of cultured mosquito cells and so may be associated only with cells with vertebrate type DNA methylation. PMID- 2901712 TI - Duplication of the bcr and gamma-glutamyl transpeptidase genes. AB - The Philadelphia (Ph') translocation involves rearrangement of the bcr gene located on chromosome 22. Hybridization experiments revealed the presence of multiple bcr gene-related loci within the human genome. Two of these were molecularly cloned and characterized. Both loci contain exons and introns corresponding to the 3' region of the bcr gene. Restriction enzyme and DNA sequence analysis indicate a very high degree of conservation between bcr and the two related genomic sequences. Both bcr-related loci are located on chromosome 22, one centromeric, the other telomeric, of the bcr gene. Within the two bcr related genomic sequences, fragments or the complete coding sequences of an unrelated gene were found to be present. This gene was identified; it encodes gamma-glutamyl transferase, an enzyme involved in the glutathione metabolism. PMID- 2901714 TI - Phage 8-9 defines a cluster of site polymorphisms on chromosome 16q22-q24 [HGM9 no. D16S20]. PMID- 2901715 TI - A highly polymorphic locus is detected by probe CARLP II6.3 [D5S88]. PMID- 2901713 TI - Use of RecA protein to enrich for homologous genes in a genomic library. AB - RecA protein-coated probe has been utilized to enrich genomic digests for desired genes in order to facilitate cloning from genomic libraries. Using a previously cloned HLA-B27 gene as the recA-coated enrichment probe, we obtained a mean 108x increase in the ratio of specific to nonspecific plaques in lambda libraries screened for B27 variant alleles of estimated 99% homology to the probe. Class I genes of lesser homology were less enriched: 6.7x for non-B27 genes of estimated greater than 95% homology and 3.7x for other-Class I genes of greater than 80% homology. Loss of genomic DNA during the enrichment procedure can, however, restrict application of this technique whenever starting genomic DNA is very limited. Nevertheless, the impressive reduction in cloning effort and material makes recA enrichment a useful new tool for cloning homologous genes from genomic DNA. PMID- 2901716 TI - HindIII polymorphism in the human c-sis proto-oncogene. PMID- 2901717 TI - XmnI RFLP at 5q13 detected by a 0.49 kb Xmn I fragment of human hexosaminidase (HEXB) cDNA. PMID- 2901718 TI - A new RFLP at the human vitamin-D binding protein (hDBP) locus. PMID- 2901719 TI - Restriction fragment length polymorphism near the IgH locus on mouse chromosome 12. PMID- 2901720 TI - A BglI polymorphism for the interleukin-2 receptor gene (IL2R) on chromosome 10. PMID- 2901721 TI - RFLP for the human transforming growth factor beta-1 gene (TGFB) on chromosome 19. PMID- 2901722 TI - A TaqI RFLP detected by the human haptoglobin (HP) cDNA probe, pULB1148. PMID- 2901723 TI - Four RFLPs of the human insulin receptor gene: PstI, KpnI, RsaI (2 RFLPs). PMID- 2901724 TI - Intrinsic polymorphism of variable number tandem repeat loci in the human genome. AB - In the human genome, short tandem repetitive (STR) DNA sequences often show restriction fragment length polymorphisms (RFLPs) due to variation in the number of copies of the repeat unit. For a subset of these sequences known as minisatellites or variable number tandem repeat loci (VNTR), it has been proposed that a homologous "core" sequence of 10-12 nucleotides is involved in the mechanism(s) generating the polymorphism. In our present study we have prepared oligonucleotide probes complementary to one or two repeat units of several VNTR loci. Under stringent hybridization and wash conditions these probes hybridize locus specifically thus allowing the evaluation of the intrinsic polymorphism of individual loci. Our results indicate that not all of the loci having STR DNA sequences are polymorphic despite the fact that they share the "core" sequence. This suggests that more than the DNA sequence of the locus is involved in the mechanism(s) generating the polymorphism. PMID- 2901725 TI - Identification of DNA sequences required for mouse APRT gene expression. AB - The mouse aprt promoter contains four GC boxes, which bind transcription factor Spl in vitro, and lacks both TATA and CCAAT boxes. Removal of the two most distal GC boxes of this promoter had little effect on APRT enzyme levels produced in a transient expression assay. Deletion of the distal three GC boxes resulted in a 50% reduction, and deletion of all GC boxes resulted in essentially complete loss of APRT activity. There are two predominant transcription start sites which are located within the region containing the GC boxes. The promoter behaved as a relatively strong promoter when compared to the RSV LTR promoter in a transient CAT assay, and operated in one orientation only. No upstream anti-sense transcripts were detected in either mouse CAK or liver cells, confirming that the mouse aprt promoter, unlike some other GC-rich promoters appears not to support bidirectional transcription. PMID- 2901726 TI - Nucleoside imidodiphosphates synthesis and biological activities. AB - The synthesis of imidodiphosphate analogues of natural nucleoside 5'-diphosphates including adenosine 5'-imidodiphosphate (4a), guanosine 5'-imidodiphosphate (4b), 2'-deoxyadenosine 5'-imidodiphosphate (4c), and 2'-deoxy-guanosine 5' imidodiphosphate (4d) has been accomplished for the first time. These compounds are the products of the reaction between nucleosides and trichloro [(dichlorophosphoryl)imido] phosphorane in trimethyl phosphate. Some of the major by-products of the reaction including 5'-deoxy-5'-chloro nucleosides are discussed. Compounds 4b, 4c, and 4d are potent inhibitors of ecto-5'-nucleotidase whereas compound 4a also active but less potent inhibitor. Compound 4b is the most potent inhibitor of phosphoribosyl pyrophosphate (PPRP) synthetase which follows by 4c, 4d and 4a. All of these compounds were more potent inhibitor of PPRP-synthetase than ADP or GDP. Ribavirin imidodiphosphate (4e) was also synthesized and tested for its inhibitory effect on ecto-5'-nucleotidase, PPRP synthetase as well as IMP dehydrogenase. Compound 4e is the most potent inhibitor of IMP dehyrogenase but was a weak inhibitor of the other two enzymes. compound 4a, 4b, 4c and 4d are weak inhibitors of IMP dehydrogenase. PMID- 2901727 TI - Highly polymorphic locus D15S24 (CMW-1) maps to 15pter-q13. [HGM9 provisional no. D15S24]. PMID- 2901728 TI - A deletion/insertion polymorphism in the human BCR gene on chromosome 22. PMID- 2901729 TI - HincII and KpnI RFLPs for laminin B1 (LAMB1) gene on chromosome 7. PMID- 2901730 TI - NcoI RFLP at the creatine kinase-muscle type gene locus (CKMM, chromosome 19). PMID- 2901731 TI - NcoI and TaqI RFLPs for human M creatine kinase (CKM) PMID- 2901732 TI - An EcoRI polymorphism for pMet G in inbred mice. PMID- 2901733 TI - Two new ApoB gene polymorphisms: Rs1 and Rs2. PMID- 2901735 TI - RsaI polymorphism of a human immunoglobulin VH5 subclass locus. PMID- 2901734 TI - Two new ApoB gene polymorphisms: Rs3 and Rs4. PMID- 2901736 TI - pmcf.2-11, a single copy clone from chromosomal region 12q12-q13.1 [D12S32]. PMID- 2901738 TI - Neuronal interactions between neuropeptide Y (NPY) and catecholaminergic systems in the rat arcuate nucleus as shown by dual immunocytochemistry. AB - Several recent studies have suggested interactions between catecholamine (CA) and neuropeptide Y (NPY) neuronal systems in the rat brain. In order to obtain morphological evidence for such CA/NPY interactions in the arcuate nucleus, we have used a double immunostaining procedure using an anti-tyrosine hydroxylase (TH) antiserum as a marker for catecholamine neurons and an anti-NPY antiserum. This double staining, where the first staining is silver-gold intensified, was detectable at both light and electron microscopic levels. In semi-thin sections, a substantial overlap and close proximity of TH-immunopositive neurons and NPY neuronal elements could be seen within the arcuate nucleus. At the electron microscopic level, direct appositions between TH- and NPY-immunoreactive structures could be detected. These appositions were of axosomatic, axodendritic or axoaxonic types without any synaptic membrane differentiation. Moreover, direct appositions between NPY-immunoreactive structures have also been observed. This morphological study showing appositions between TH and NPY neuronal systems suggest direct interactions between these two systems in the arcuate nucleus. PMID- 2901737 TI - Superactive somatostatin analog decreases plasma glucose and glucagon levels in diabetic rats. AB - The action of the new analog of somatostatin, D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp NH2 (RC-160), on plasma glucagon and glucose levels was evaluated in streptozotocin-diabetic rats. The effect of this analog on the insulin-induced hypoglycemia in diabetic rats was also investigated in order to evaluate the risk of exacerbating hypoglycemia. Administration of analog RC-160, in a dose of 25 micrograms/kg b. wt. SC, inhibited plasma glucagon secretion and decreased plasma glucose levels. This effect also occurred when plasma glucagon and glucose levels were first elevated by arginine infusion, 1000 mg/kg/hr for 30 min. Subcutaneous injection of regular insulin, 15 U/kg b. wt., produced hypoglycemia with a progressive increase in glucagon levels. Analog RC-160 completely suppressed the hypoglycemia-induced glucagon release for up to 150 min after injection of the analog or insulin. A greater decrease in the plasma glucose level was observed in the group treated with insulin and the analog than in the group injected only with insulin. These results indicate that somatostatin analog RC-160 can produce a marked and prolonged inhibition of glucagon release and a decrease in the plasma glucose level in diabetic rats. This analog may be useful as an adjunct to insulin in the treatment of diabetic patients, although caution should be exercised, to prevent hypoglycemia when using somatostatin analogs together with insulin. PMID- 2901739 TI - Identification of immunoreactive somatostatin in the rat harderian gland: regulation of its content by growth hormone, beta-adrenergic agonists and calcium channel blockers. AB - Immunoreactive somatostatin (IRS) was identified in the male rat Harderian gland (HG) by radioimmunoassay. Tissue was extracted and a displacement curve performed; there were no significant differences between values obtained with serial dilutions of extracted tissue and those from purified somatostatin standard used in the radioimmunoassay. Basal values of HG-IRS were found to be in the nanomolar range (10.8 +/- 3.5 ng IRS/mg protein). Hypophysectomy did not change the HG-IRS but, in vivo growth hormone (GH) treatment led to a dramatic increase (6-7-fold) in the levels of IRS in the HG. Isoproterenol, a beta adrenergic agonist, when administered in vivo significantly decreased the HG-IRS content. The effect of two different calcium channel blockers on the isoproterenol-induced decrease of HG-IRS was studied; no changes were observed with nifedipine but verapamil, injected one hour after isoproterenol administration, prevented the drop in HG-IRS levels. These data demonstrate the existence of IRS in a new location, the rat Harderian gland, and support a classical endocrine regulation for its tissue concentration. PMID- 2901741 TI - The quest to establish the neural substrates of anxiety. AB - Recent developments in neuroanatomic, lesion and stimulation, and functional brain mapping studies offer great promise in the search for the neural substrates of anxiety. Animal studies have provided important clues about the neural pathways that underlie certain aspects of the evaluative and expressive components of anxiety. As a brain-imaging technique that safely permits the study of the living human brain, positron emission tomography is likely to provide additional information about the neural structures that underlie the evaluation, expression, and experience of anxiety in each of its normal and pathologic forms. The quest to establish the neural substrates of anxiety has two parts: identification of the elementary psychophysiologic operations that define anxiety and identification of the precise neural pathways that underlie each of these operations. To paraphrase an investigator who is involved in this quest, the challenge and charm of this field are that studies of both the mind and the brain are required. PMID- 2901740 TI - Cortical amino acid neurotransmitter release is altered by CCK perfused in frontal region of unrestrained aged rats. AB - The purpose of this study was to investigate in the aged animal the functional interaction between cholecystokinin (CCK) and amino acid neurotransmitter activity in the frontal cortex, a structure of importance in age-related disabilities. Guide cannula for repeated push-pull perfusion were implanted bilaterally in the superficial frontal cortex of male Sprague-Dawley rats. Two groups of animals were selected on the basis of their age at the time of stereotaxic surgery: 90 days and two years. Following post-operative recovery, an artificial CSF solution was perfused repeatedly within the cortex of each animal for a 5.0 min interval. The rate of perfusion was 25 microliters/min and a 5.0 min period elapsed between the collection of each sample of perfusate. After the initial control perfusions, CCK octapeptide was incorporated in a concentration of 6.0 or 18.0 ng/microliter in the CSF and perfused for 5.0 min under identical conditions. Each sample of perfusate was assayed by high performance liquid chromatography with electrochemical detection (HPLC-EC) for its content of glutamate (Glu), aspartate (Asp), glutamine (Gln), glycine (Gly), taurine (Tau) and gamma-amino-butyric acid (GABA) with homoserine used as an internal standard. Although CCK in the lower 6.0 ng/microliter concentration failed to alter significantly the profile of amino acids in the frontal cortex, the higher 18.0 ng/microliter solution of CCK enhanced the efflux of Glu as well as Asp, but only in the aged rats. Both concentrations of CCK tended also to augment the release of Gln in the older animals but these changes were not statistically significant. Both Gly and Tau were unaffected by CCK in either dose in both the young and old groups. GABA was not detectable in any of the samples of perfusate throughout the experiments. These results suggest that CCK-8 exerts a selective effect on amino acid neurotransmitter activity in the frontal cortex which is clearly age dependent. In the older animal, this sensitivity of the cortical cells to CCK may reflect a functional attribute of the peptide in the aging process. PMID- 2901742 TI - Collagenous colitis with rapid response to sulphasalazine. AB - A case of collagenous colitis in a young female with a rapid response to sulphasalazine both symptomatically and histologically is reported. This is only the third such response to be reported. In most published accounts, collagenous colitis fails to respond to treatment and runs a very prolonged course. PMID- 2901744 TI - Intermittent treatment of duodenal ulcer for long term medical management. AB - Most patients with duodenal ulcer relapse but in individuals the events is unpredictable and complications are rare. Two methods of long term treatment have been developed: daily maintenance treatment to prevent relapse; and intermittent treatment, in which individual symptomatic relapses are treated with a short healing course. Pooling the results of three studies on intermittent treatment where cimetidine was used, the number of relapses in one year and the proportion of patients who relapsed were: no relapse, 26%; 1 relapse, 33%; 2 relapses, 24%; greater than or equal to 3 relapses, 17%. Thus, 83% of patients on average have less than or equal to 2 attacks per year, which can be rapidly controlled with a short course of treatment. In comparative trials, relapse on maintenance treatment is much less than on intermittent treatment, as would be expected, but the clinical advantage of the former is relatively small and obtained at a much higher cost in drugs. However, in practice, the two treatments are complementary, not competitive, and patients in whom maintenance treatment (or surgery) is necessary would not be considered for intermittent treatment. Most work on intermittent treatment has been done with histamine H2 receptor antagonists. Theoretically, better results might be achieved by increasing the healing rate with omeprazole or more effectively, by reducing the spontaneous relapse rate by healing with colloidal bismuth. Intermittent treatment is contraindicated in the one-third who are either 'high-risk' patients or those who have aggressive ulcer disease. It is suitable for the two-thirds who meet all the following criteria: age <60 years; no associated serious illness; no previous haemorrhage or perforation; not on regular treatment with non-steroidal anti-inflammatory drugs; symptoms develop gradually (se that treatment can be started before pain worsens); less than or equal 2 relapses per year; ulcer is non-refractory. It is essential to establish an accurate diagnosis before starting therapy. Treatment is given for a month and repeated when typical symptoms recur. Repeat endoscopy is not needed except in special circumstances. For the majority of patients, intermittent treatment is an effective, simple and economical way of providing long term treatment. PMID- 2901743 TI - Protective effects against alcohol insult: does somatostatin play any role? AB - This study evaluated the cytoprotective properties of misoprostol, a synthetic prostaglandin E1 analogue and cimetidine, against alcohol-induced gastric mucosal injury and examined the role of increased gastric juice somatostatin in cytoprotection. Forty-give healthy adult male volunteers were enrolled in a randomized, double-blind, placebo-controlled endoscopic study. Screening endoscopy was done to exclude subjects with asymptomatic gastric mucosal abnormality. Misoprostol (200 micrograms) intragastrically, cimetidine (300 mg) orally or placebo were administered prior to ethanol challenge. Injury to the gastric mucosa was produced by spraying it with 80% ethanol solution instilled intragastrically. Endoscopic evaluation of gastric mucosa was conducted 15 and 30 minutes after ethanol by two endoscopists independently according to a seven point scale. Thirty minutes following the instillation of ethanol, gastric contents were aspirated and analysed for immunoreactive somatostatin. The gastric mucosa of placebo-treated subjects showed marked damage with endoscopic score (mean +/- standard deviation) of 5.5 +/- 0.9. Cimetidine partially prevented gastric mucosal damage with endoscopic score of 4.5 +/- 1.7 as compared to placebo (P = 0.04). Misoprostol prevented significant gastric mucosal injury, (endoscopic score of 1 +/- 1.7) when compared to placebo (P = 0.0001) and to cimetidine (P = 0.0002). The gastric juice somatostatin concentration (pg/ml) was 75.79 +/- 13.59 in the misoprostol group, 64.71 +/- 8.06 in the cimetidine group and 34.34 +/- 5.66 in the placebo group. Both misoprostol and cimetidine showed significant (P = 0.05) increase in gastric juice somatostatin when compared to placebo treatment. The degree of gastric mucosal protection afforded by misoprostol was significantly greater than cimetidine. Since gastric juice somatostatin in the misoprostol group was not significantly different from the cimetidine group, it was concluded that gastric juice somatostatin is not solely responsible for the cytoprotective ability of misoprostol. PMID- 2901745 TI - [In pursuit of excellence: raising the standards of clinical practice in nursing]. PMID- 2901746 TI - Mechanism of action of the mitochondrial proton pumping ATPase in ATP synthesis and hydrolysis. PMID- 2901747 TI - Rapid kinetics measurements of Mg2+ and Ca2+ ions release from CF1-ATPase. PMID- 2901748 TI - The vacuolar H+-ATPase, a proton pump controlled by a slip. PMID- 2901749 TI - Allosteric short-term regulation of ATP synthase: a plausible model. PMID- 2901750 TI - High yield incorporation of the Neurospora plasma membrane H+ATPase into proteoliposomes: lipid requirement and secondary structure of the enzyme by IR spectroscopy. PMID- 2901751 TI - Proton-ATPases: universal catalysts in biological energy conservation. PMID- 2901752 TI - Structure of the ATP-synthase from chloroplasts as revealed from biochemical studies and electron microscopy. PMID- 2901753 TI - Structure of the ATP-synthase from chloroplasts studied by electron microscopy and image processing. PMID- 2901754 TI - Dissociation-reconstitution experiments with NBD-modified F1: support for the presence of two catalytic beta-subunits. PMID- 2901755 TI - Mitochondrial ATP synthase: role of metal binding in structure and function. PMID- 2901756 TI - Behavioural and EEG effects of some excitatory amino acid antagonists. PMID- 2901757 TI - Evidence for a regulatory role of alpha-2 receptors on gastric acid secretion and gastrin release in the dog. PMID- 2901758 TI - Antagonism of clonidine-induced hypothermia by alpha adrenoceptor antagonists in electrically stimulated mice. AB - The involvement of receptor subtypes in clonidine-induced hypothermia in electrically stimulated mice was studied using various alpha-adrenoceptor antagonists. Yohimbine, the selective alpha 2-adrenoceptor antagonist significantly blocked the action of low dose (50 micrograms/kg i.p.) of clonidine pretreated with Minimal Threshold Shock (12 mA, 0.2 Sec), while prazosin, selective alpha 1-adrenoceptor antagonist partially blocked the action, suggesting predominant involvement of alpha 2 and partial involvement of alpha 1 adrenoceptors. Under similar conditions when clonidine was used in higher dose (500 micrograms/kg i.p.), its action was blocked by prazosin, phenoxybenzamine and yohimbine suggesting involvement of both alpha 1 and alpha 2-adrenoceptors. In case of animals pretreated with Maximal Threshold Shock (36 mA, 0.2 Sec) the hypothermic action of clonidine in lower dose was blocked by all the three antagonists viz. prazosin, phenoxybenzamine and yohimbine, suggesting involvement of both alpha 1 and alpha 2-adrenoceptors, however, when clonidine was used in the higher dose, the action was significantly antagonised by prazosin and partially by yohimbine, suggesting predominant involvement of alpha 1 and partial involvement of alpha 2-adrenoceptors. PMID- 2901759 TI - Differential alteration in striatal dopaminergic and cortical serotonergic receptors induced by repeated administration of haloperidol or centbutindole in rats. AB - Centbutindole is a new neuroleptic drug having a pharmacological profile similar to haloperidol, but it does not cause hypothermia and has a higher separation between doses causing catalepsy and neurolepsy. The interactions of centbutindole with striatal dopamine and cortical 5-HT2 receptors have been studied along with haloperidol following 3 weeks of administration. Rats received haloperidol (1.0 mg/kg, p.o.), centbutindole (0.5 mg/kg, p.o.) or saline daily for 21 days. Following drug withdrawal for 3 days, apomorphine (0.1-1.0 mg/kg, i.p.) or 5 hydroxytryptamine (5-HTP, 50-200 mg/kg, i.p.) was injected. Apomorphine-induced stereotyped behaviour was potentiated in the haloperidol-treated rats, while the 5-HTP-induced behavioural syndrome was increased in centbutindole-treated rats. Receptor binding studies indicated an increase in the maximal binding capacity Bmax of striatal dopamine receptor (29.4%) in haloperidol-treated and of cortical 5-HT2 receptor (17.8%) in centbutindole-treated animals. No change in the apparent dissociation constant Kd was observed. It is concluded that repeated treatment with haloperidol produced striatal dopamine receptor supersensitivity while centbutindole treatment produced cortical serotonergic receptor supersensitivity. PMID- 2901760 TI - Mutational analysis of the yeast coenzyme QH2-cytochrome c reductase complex. AB - The synthesis of cytochrome b in yeast depends on the expression of both mitochondrial and nuclear gene products that act at the level of processing of the pre-mRNA, translation of the mRNA, and maturation of the apoprotein during its assembly with the nuclear-encoded subunits of coenzyme QH2-cytochrome c reductase. Previous studies indicated one of the nuclear genes (CBP2) to code for a protein that is needed for the excision of the terminal intervening sequence from the pre-mRNA. We show here that the intervening sequence can promote its own excision in the presence of high concentrations of magnesium ion (50 mM), but that at physiological concentrations of the divalent cation (5 mM), the splicing reaction requires the presence of the CBP2-encoded product. These results provide strong evidence for a direct participation of the protein in splicing, most likely in stabilizing a splicing competent structure in the RNA. The conversion of apocytochrome b to the functional cytochrome has been examined in mutants lacking one or multiple structural subunits of the coenzyme QH2-cytochrome c reductase complex. Based on the phenotypes of the different mutants studied, the following have been concluded. (i) The assembly of catalytically active enzyme requires the synthesis of all except the 17 kDa subunit. (ii) Membrane insertion of the individual subunits is not contingent on protein-protein interactions. (iii) Assembly of the subunits occurs in the lipid bilayer following their insertion. (iv) The attachment of haem to apocytochrome b is a late event in assembly after an intermediate complex of the structural subunits has been formed. This complex minimally is composed of apocytochrome b, the non haem iron protein and all the non-catalytic subunits except for the 17 kDa core 3 subunit. PMID- 2901761 TI - Import of proteins into mitochondria. AB - A mounting body of evidence suggests that cytoplasmically synthesized proteins destined to be imported into the mitochondrial interior must at least partly unfold to penetrate across the mitochondrial membranes. During post-translational import, this unfolding process appears to be a major rate-limiting step. It can be blocked by ligands that stabilize the protein's native conformation and appears to be accompanied by the cleavage of ATP outside the mitochondrial inner membrane. PMID- 2901762 TI - A path from mitochondria to the yeast nucleus. AB - We have identified a path in yeast, from mitochondria to the nucleus, which may have a regulatory function in mitochondrial biogenesis. This path is evident as an elevated expression of a number of nuclear DNA sequences in response to specific defects in the mitochondrial genome, including the absence of mitochondrial DNA in rho 0 petites. Among those nuclear sequences preferentially expressed in certain respiratory-deficient cells are stable poly(A)+ transcripts derived from the so-called non-transcribed spacer region of the nuclear ribosomal DNA repeat, where they are most abundant in the rho 0 petite. Although the function of these unusual RNAs is unclear, the observations may reflect the presence of a mitochondrial homeostatic control system in yeast, which we suggest could function to adjust the mass of mitochondria and mitochondrial DNA in the cell in response to inequities in organelle apportionment during cell budding. PMID- 2901763 TI - Organization and expression of algal (Chlamydomonas reinhardtii) mitochondrial DNA. AB - The mitochondrial genome of Chlamydomonas reinhardtii, a unicellular green alga, is a linear 15.8 kilobase pair (kbp) molecule. In gene arrangement and mode of expression, as well as in size, it differs radically from the large (200-2400 kbp) mitochondrial genomes of higher plants. Heterologous hybridization experiments and nucleotide sequence analysis have revealed that C. reinhardtii mitochondrial DNA (mtDNA) is a compactly organized genome specifying at least eight proteins, a minimum of three transfer RNAs, and large subunit (LS) and small subunit (SS) ribosomal RNAs. Both strands of the mtDNA encode genetic information, with genes organized into perhaps a single transcriptional unit on each strand. Stable transcripts have been identified by Northern hybridization analysis, and transcript termini have been mapped by primer extension and S1 nuclease protection experiments. The results suggest that mature RNAs, which virtually saturate the genome, are generated by precise endonucleolytic cleavage of long precursors, with specific motifs (both primary sequence and secondary structure) implicated as processing signals. Codon usage in C. reinhardtii mitochondria is highly biased, with eight codons entirely absent from all protein coding genes; however, even though codon usage is restricted, it appears that C. reinhardtii mtDNA cannot encode the minimum number of tRNAs needed to support mitochondrial protein synthesis. The most striking feature of C. reinhardtii mtDNA is the division of SS and LS rRNA genes into a number of separate subgenic coding segments ('modules') that are interspersed with one another and with protein-coding and tRNA genes. We have identified abundant small RNAs, transcribed from these modules, that approximate to the latter in size. This indicates that splicing of rRNA 'pieces' does not occur in this system. Rather, the mature rRNAs apparently exist and function as non-covalent complexes of small RNAs (four in SS rRNA, at least eight in LS rRNA), held together by intermolecular base pairing. These complexes contain all the conserved elements of the minimal secondary structures that define the functional core of conventional LS and SS rRNAs. PMID- 2901764 TI - Recombination is associated with polymorphism of the mitochondrial genomes of maize and sorghum. AB - Extensive recombination events characterize higher-plant mitochondrial DNAs. Numerous recombination events resulted in the appearance of an unusual mitochondrial open reading frame, urf13-T, which encodes a 13 kDa polypeptide in the male-sterile T cytoplasm of maize. Maize lines with T cytoplasm are unusually susceptible to two fungal pathogens which produce host-selective toxins. Mutants derived from tissue culture expressing male fertility and toxin-insensitivity are characterized by truncation or deletion of urf13-T. These events result from a frameshift associated with a tandem 5 base pair repeat, placing a premature stop codon in frame, or from a recombination event, apparently limited to tissue culture, resulting in the deletion of urf13-T. Neither class of mutants produces the 13 kDa gene product. Repeated sequences that participate in recombination in sorghum appear to be randomly distributed among male-fertile or male-sterile cytoplasms. Processes involved in the evolution of mitochondrial DNAs in higher plants therefore include the generation and deletion of configurations through recombination. PMID- 2901765 TI - Mitochondrial biogenesis. PMID- 2901766 TI - Translational regulation of mitochondrial gene expression by nuclear genes of Saccharomyces cerevisiae. AB - We describe several yeast nuclear mutations that specifically block expression of the mitochondrial genes encoding cytochrome c oxidase subunits II (COXII) and III (COXIII). These recessive mutations define positive regulators of mitochondrial gene expression that act at the level of translation. Mutations in the nuclear gene PET111 completely block accumulation of COXII, but the COXII mRNA is present in mutant cells at a level approximately one-third of that of the wild type. Mitochondrial suppressors of pet111 mutations correspond to deletions in mtDNA that result in fusions between the coxII structural gene and other mitochondrial genes. The chimeric mRNAs encoded by these fusions are translated in pet111 mutants; this translation leads to accumulation of functional COXII. The PET111 protein probably acts directly on coxII translation, because it is located in mitochondria. Translation of the mitochondrially coded mRNA for COXIII requires the action of at least three nuclear genes, PET494, PET54 and a newly discovered gene, provisionally termed PET55. Both the PET494 and PET54 proteins are located in mitochondria and therefore probably act directly on the mitochondrial translation system. Mutations in all three genes are suppressed in strains that contain chimeric coxIII mRNAs with the 5'-untranslated leaders of other mitochondrial transcripts fused to the coxIII coding sequence. The products of all three nuclear genes may form a complex and carry out a single function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901767 TI - Hybridization analysis of the class P tetracycline resistance determinant from the Clostridium perfringens R-plasmid, pCW3. AB - The tetracycline resistance determinant from pCW3, a conjugative plasmid from Clostridium perfringens, has been identified and the structural gene localized to within a 1.4-kb region. Hybridization analysis, which utilized an internal 0.8-kb specific gene probe, showed that eight nonconjugative tetracycline resistant C. perfringens strains all carried homologous resistance determinants. No homology was detected in DNA prepared from tetracycline resistant isolates of Clostridium difficile or Clostridium sporogenes. However, the one strain of Clostridium paraputrificum that was tested did contain an homologous determinant. No homology was found to any of the recognized classes of tetracycline resistance determinants. The C. perfringens tetracycline resistance determinant represents a new hybridization group, Class P. PMID- 2901768 TI - Complete nucleotide sequence and genetic organization of the bacteriocinogenic plasmid, pIP404, from Clostridium perfringens. AB - The complete nucleotide sequence of the bacteriocinogenic plasmid, pIP404, from Clostridium perfringens has been determined. The plasmid genome comprises 10,207 bp and has a dA + dT content of 75%. Functions have been tentatively assigned to 6 of the 10 open reading frames and an origin-like region of repeated sequence identified. The codon usage of this extremely dA + dT rich plasmid is highly unusual and displays a pronounced preference for codons with the lowest dG + dC content. Only one of the genes from pIP404 was expressed at a significant level in Escherichia coli, suggesting that the atypical codon usage could represent a major obstacle to heterologous gene expression. PMID- 2901769 TI - Identification and molecular genetic analysis of replication functions of the bacteriocinogenic plasmid pIP404 from Clostridium perfringens. AB - The replication functions of the bacteriocinogenic plasmid pIP404, from Clostridium perfringens, were localized to a 2.8-kb EcoRI-EcoRV fragment by cloning into a vector deficient for replication in Bacillus subtilis. This fragment contains two genes, cop and rep, which encode proteins and an 800-bp noncoding segment of complex structure consisting of multiple tandemly repeated sequences. The Cop protein is involved in copy number control, whereas the rep gene product is essential for plasmid replication. By deletion analysis the minimal origin of replication was defined as the rep gene plus most of the repeated sequences. A powerful promoter producing a 150-nucleotide RNA molecule, RNA1, that could act as an anti-sense RNA to the rep gene was detected in the "origin-like" region. In contrast to most other small plasmids of gram-positive bacteria, pIP404, and its derivatives, does not appear to replicate via a single stranded intermediate in either C. perfringens or B. subtilis. PMID- 2901770 TI - The Clostridium perfringens chloramphenicol resistance transposon Tn4451 excises precisely in Escherichia coli. AB - Nucleotide sequence analysis of the Tn4451-deletion derivatives, pJIR47 and pJIR86, which were derived from Escherichia coli and Clostridium perfringens, respectively, showed that the deletion events that led to the formation of these plasmids were identical and precise. The results also showed that the termini of this C. perfringens-derived transposon contained imperfect 12-bp inverted repeat sequences which had some sequence similarity with the termini of Tn3-like transposons. PMID- 2901771 TI - Cloning and partial characterization of three small cryptic plasmids from Bacillus thuringiensis. AB - The strain H1.1 of Bacillus thuringiensis var. thuringiensis harbors three small cryptic plasmids: pGI1, pGI2, and pGI3 (8.2, 9.2, and 10.6 kb, respectively). Two of these plasmids (i.e., pGI2 and pGI3) were successfully cloned in their entirety into the vector pBR322, whereas only overlapping DNA fragments covering pGI1 were obtained in Escherichia coli. A curing-hybridization technique was used to obtain isolates of B. thuringiensis missing one or another small cryptic plasmid. These derivatives were examined for any change in a phenotypic trait, but no specific function could be assigned to one of these plasmids. Hybridization and restriction mapping data revealed that the transposon Tn4430 accounts for 45% of the pGI2 plasmid DNA. PMID- 2901772 TI - Introduction of the Streptococcus faecalis transposon Tn916 into Bacillus thuringiensis subsp. israelensis. AB - The conjugative Streptococcus faecalis transposon Tn916 was introduced into Bacillus thuringiensis subsp. israelensis by filter matings with S. faecalis. B. thuringiensis transconjugants resistant to tetracycline (Tetr) were detected at a frequency of approximately 7.0 X 10(-7) per recipient cell during filter matings, whereas transfer of Tn916 was not observed in broth matings. The Tetr phenotype in subsp. israelensis was stable in the absence of antibiotic selection. Southern hybridization analysis revealed that Tn916 had inserted into several different sites on the B. thuringiensis subsp. israelensis chromosome but insertion into plasmid DNA was not observed. Movement of Tn916 was demonstrated when Tetr B. thuringiensis transconjugants were mated with isogenic recipients. Southern hybridizations, however, showed that the resulting Tetr isolates contained Tn916 junction fragments that were nearly identical to the donor, suggesting that this movement resulted from transfer of chromosomal DNA from donor to recipient or from a fusion of mating cells, rather than conjugative transposition of the Tn element. PMID- 2901773 TI - Familial and sporadic medullary thyroid carcinoma: clinical and immunohistological findings. AB - We have studied the clinical and thyroid immunohistological features of 19 patients with sporadic medullary thyroid carcinoma and 16 patients with the hereditary syndrome multiple endocrine neoplasia 2a (MEN 2a). Both groups were identified by family screening using serum calcitonin determinations before and after pentagastrin stimulation. Pheochromocytoma and hyperparathyroidism were associated both with multiple endocrine neoplasia 2a and some cases of sporadic medullary thyroid carcinoma. Hereditary medullary thyroid carcinoma was invariably associated with C-cell hyperplasia, but C-cell hyperplasia was also associated with some sporadic tumours. All tumours were positive for calcitonin and carcinoembryonic antigen (by immunohistological staining) (CEA) and most tumours stained for somatostatin. C-cell hyperplasia also stained for calcitonin, CEA and somatostatin. We conclude that sporadic and familial medullary thyroid carcinoma cannot always be discriminated by clinical or immunohistological methods. Family screening is essential in the diagnosis of hereditary medullary thyroid carcinoma. PMID- 2901774 TI - Simultaneous localization of a classical neurotransmitter (GABA) and a peptide transmitter candidate (proctolin) in the nervous system of the cockroach, Periplaneta americana. AB - The distribution of the neurotransmitter gamma-aminobutyric acid (GABA) in the 6th abdominal ganglion of the cockroach Periplaneta americana was investigated using an antiserum against GABA. The high number of GABA immunoreactive neurons refer to the important function of this transmitter substance. The relation between the GABAergic system and the proctolinergic system in the 6th abdominal ganglion was examined by means of an immunohistochemical double staining technique. The results show that probably GABA and proctolin do not coexist within one neuron. PMID- 2901775 TI - [Immunocytochemical studies of the development of basal cell types of human islet organs]. AB - The investigations are carried out in 19 human fetal pancreases. The detection of the 4 islet hormones insulin, glucagon, somatostatin and PP ist carried out in PAP-technique. The parts of these 4 types of islet cells are estimated quantitatively. In the 10th to 15th week of development insulin-producing B-cells are present. Moreover glucagon-, somatostatin- and PP-cells in the islet organ are present. In the group of 16th to 20th week of gestation insulin-, glucagon- and somatostatin-cells are increased compared to the first group. PP-cells are not altered. The increase of 3 types of islet cells is a result of fetal development. PMID- 2901776 TI - Long-lasting changes after perinatal exposure to antidepressants. PMID- 2901778 TI - Neurotransmitters as morphogens. PMID- 2901777 TI - Alcohol as a social teratogen. PMID- 2901779 TI - Use of toxins to disrupt neurotransmitter circuitry in the developing brain. PMID- 2901781 TI - [The enzymes and genes participating in DNA replication of animal cells. PCNA/DNA polymerase delta auxiliary protein and molecular cloning of the gene]. PMID- 2901780 TI - Prenatal neurotransmitter programming of postnatal receptor function. PMID- 2901782 TI - [Abdominal aortic aneurysm, retroperitoneal fibrosis and vasculitis]. PMID- 2901783 TI - The nurse's guide to cardiovascular drugs. Part II (continuing education credit). PMID- 2901784 TI - Effect of acid inhibition on Campylobacter pylori. AB - Campylobacter pylori (Cp) infection has been demonstrated in 59 of 65 (91%) patients with gastric or duodenal ulcer. Patients were included in a double blind study with ranitidine or famotidine for 4-8 weeks. After therapy, all gastric and duodenal ulcers healed but Cp remained in all previously infected patients, associated with chronic inflammation of gastric mucosa. Our results suggest that H2 antagonists do not have any effect either on Cp infection or on concurrent chronic gastritis. At the same time we observed that Cp infection does not disturb the ulcer healing process. However, Cp may be implicated in the persistence of the chronic gastritis and relapses of ulcers. PMID- 2901785 TI - Cytoprotective agents and C. pylori associated acid peptic diseases. PMID- 2901786 TI - The assay for thyroid stimulating immunoglobulin using cultured human thyroid cells and its clinical application. AB - A new technique for the determination of the serum level of thyroid stimulating immunoglobulins (TSI) is described. TSI may be detected by measuring cyclic AMP increases in cultures of isolated thyroid epithelial cells in response to added normal or patient's serum. Our results showed that the serum level in the normal control group was mostly lower than 110%, however, in 9.1% of normal human sera, TSI showed a positive result. In abnormal position, activity of TSI was higher than 110% of the rate of the normal control group. The positive result was 86% and the serum TSI levels were 270 +/- 176.6% in patients with Graves' disease before receiving antithyroid drug. After treatment with antithyroid drugs from one to thirty months, the positive results dropped to 35% and the serum TSI level decreased to 117.0 +/- 113%, which was significantly lower than that in untreated patients. In conclusion, TSI can be detected in the majority of the sera in patients with Graves' disease using this technique. It is helpful to the diagnosis and treatment of the Graves' disease. PMID- 2901787 TI - HTLV-I-associated myelopathy in Natal. PMID- 2901788 TI - Splenectomy for immune thrombocytopenia related to human immunodeficiency virus. AB - From 1 January 1984 to 31 August 1987, 11 patients underwent splenectomy for treatment of thrombocytopenia related to human immunodeficiency virus (HIV). Six of the patients had been previously treated with prednisone, five of whom showed some response. None of those who responded to the prednisone had a sustained response and, thus, all required splenectomy. All 11 patients had an excellent response to splenectomy. The average preoperative and postoperative platelet counts were 19,700 and 498,000, respectively. All patients have maintained normal platelet counts at an average follow-up period of 12.4 months (range of one to 37 months). There were no postoperative deaths. Morbidity was minimal; in two patients, wound seromas developed. In one patient, acquired immunodeficiency syndrome (AIDS) developed 12 months after splenectomy, but none of the other patients have evidence of AIDS. Splenectomy is a safe and effective therapy for HIV-related immune thrombocytopenia. PMID- 2901789 TI - Transplantation of cultured human adrenal chromaffin cells into 6-hydroxydopamine lesioned rat brain. AB - Adult young rats were subjected to a unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine pathway and then given intrastriatal grafts of human fetal adrenal chromaffin cell cultures. Amphetamine-induced ipsiversive turning behavior in the lesioned rats was largely reversed in four of eight rats given such transplants when tested at 1.5 and 4.5 months post-transplantation. Two rats showed a transient recovery at 1.5 months followed by deterioration at 4.5 months, while two other rats showed continuous deterioration. Six rats given sciatic nerve grafts as controls all showed deterioration from the pretransplantation levels. Catecholamine fluorescent and immunohistochemical examination of chromaffin-cell-transplanted brains demonstrated neurons and neuronal processes positive for catecholamines or tyrosine hydroxylase in the transplanted area. This transplantation of cultured human fetal cells to an animal model may provide the necessary basic experimental system for assessing the possible utility of human neuronal transplants. PMID- 2901790 TI - Changes in synaptic morphology associated with presynaptic and postsynaptic activity: an in vitro study of the electrosensory organ of the thornback ray. AB - The influence of synaptic activity on synaptic structure was studied by selectively stimulating the presynaptic or postsynaptic membranes of ribbon synapses in an in vitro preparation, and examining the ultrastructure of synapses with conventional electron microscopic methods. Functionally significant changes in synaptic morphology were observed after direct depolarization of the presynaptic membrane or incubation with the neurotransmitter glutamate to depolarize the postsynaptic membrane. After depolarizing the presynaptic membrane for 30 seconds, the depth of the postsynaptic trough was reduced, and other morphological changes correlated with decreased sensitivity and spontaneous activity were evident. Depolarizing the postsynaptic membrane by incubating synapses with the neurotransmitter glutamate, produced opposite effects. These results suggest that synapses can undergo functionally significant morphological changes in response to certain patterns of activity. The mechanism for these changes might include synaptic vesicle recycling processes, changes in ion concentration, or cytoskeletal alterations in the presynaptic, postsynaptic, or support cells. These mechanisms could operate in association with long-term changes in synaptic efficacy or account for some physiological phenomena such as synaptic fatigue or accommodation. PMID- 2901791 TI - Glutamic acid decarboxylase- and peptide-immunoreactive neurons in cortex cerebri following development in isolation: evidence of homotypic and disturbed patterns in intraocular grafts. AB - Fetal parietal cerebral cortex was transplanted to the anterior eye chamber of adult Sprague-Dawley rats. After two to three months the grafts, with or without colchicine treatment, were subjected to immunohistochemical analysis using antibodies against cholecystokinin (CCK), somatostatin (SOM), neuropeptide tyrosine (NPY), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI) and the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). Cerebral cortex in situ of untreated and colchicine-treated rats was always analyzed in parallel. A dense plexus of CCK-immunoreactive fibers was distributed in all parts of the transplants, and after colchicine treatment a large number of CCK-positive cells was observed. These cells were markedly increased in number as compared to normal cortical tissue in colchicine pretreated rats. The amount of NPY-immunoreactive cells was also markedly increased, whereas somatostatin-positive cells were found in numbers similar to those seen in cortex in situ. In the grafts only a few VIP- and PHI-positive fibers were seen with a few VIP-positive cell bodies, but no clearly discernible PHI-positive cells. A very dense plexus of GAD-positive fibers with an even distribution throughout the grafts was observed. Cortex in situ exhibited a lower density of GAD-immunoreactive fibers. Even after colchicine treatment the number of GAD-positive cells in the grafts was low. Using double-staining techniques, it was found that most of the few GAD-positive cells in the grafts were also NPY positive, SOM-positive or, to a minor extent, CCK-positive. The present results demonstrate that several peptides and transmitter markers are expressed in cortical grafts in oculo, but marked differences in their expression can be observed in cortical tissue that has developed in isolation. Thus, the intraocular cortex graft, alone and in combination with other brain areas, should provide a useful model in which to study factors that regulate brain development. PMID- 2901792 TI - Organization of glutamate-like immunoreactivity in the rat superficial dorsal horn: light and electron microscopic observations. AB - Glutamate has been shown to be a neurotransmitter in the central nervous system of vertebrates, and it has been hypothesized that glutamate is functional as a neurotransmitter in the spinal cord dorsal horn. A monoclonal antibody to fixative-modified glutamate was used in this study to examine the light microscopic and ultrastructural profiles of glutamate-like immunoreactivity in the superficial dorsal horn of the rat spinal cord. Glutamate-like immunoreactivity was observed in neurons, fibers, and terminals of both laminae I and II. Marginal zone immunoreactive neurons ranged from 10 to 30 micron in diameter and received many nonimmunoreactive somatic synapses. In substantia gelatinosa, immunoreactive neurons were observed in both inner and outer layers, ranged 5 to 10 micron in diameter, and received few nonimmunoreactive somatic synapses. Glutamate-like immunoreactive dendrites were observed in both laminae and were contacted primarily by nonimmunoreactive synaptic terminals that generally contained small clear vesicles. Both myelinated and unmyelinated immunoreactive axons were observed in Lissauer's tract. Immunoreactive terminals contained small (40 nm) clear vesicles and generally formed simple synaptic contacts with nonimmunoreactive dendrites in laminae I and II. The results of this study corroborate the importance of glutamate as a neurotransmitter in spinal sensory mechanisms. PMID- 2901793 TI - Changes in neurotransmitter uptake in the spinal cord following peripheral nerve injury. AB - Changes in neurotransmitter systems of the spinal cord were studied in response to peripheral nerve injury. The uptake and compartmentalization of radiolabeled spinal cord neurotransmitters and transmitter precursors were examined as a function of time following unilateral sciatic nerve crush in adult mice. Accumulation of transmitter was measured within synaptosomally enriched fractions prepared using combinations of differential and density gradient centrifugations. The amount of transmitter substance recovered from these fractions was strongly dependent upon the amount of time following nerve injury and on the specific transmitter or precursor being examined (GABA, glutamate, glycine, and choline chloride). However, for each of these substances, uptake values returned to control levels within nine to twelve days after nerve crush. Localization of GABA changes postcrush revealed reciprocal differences between ipsilateral and contralateral sides of the spinal cord, as well as differences between segmental levels. Altered GABA uptake may reflect changes in the postcrush microchemical environment present during tissue processing, but may also be related to direct changes in the synaptic binding, transport, and compartmentalization of transmitter substance. The time course, magnitude, and direction of these neurochemical changes follow those observed neurophysiologically, and may thus underlie injury-induced short-term (days) alterations reported in primary afferent depolarizations, cross cord responses, and other spinal mechanisms. PMID- 2901794 TI - [Visual hallucinations and carpipramine]. PMID- 2901795 TI - [Use of IR spectrophotometry for establishing cordanum in cadaveric material]. PMID- 2901796 TI - Malaria and urbanization in central Africa: the example of Brazzaville. Part II: Results of entomological surveys and epidemiological analysis. AB - 92 night-bite collections on human bait (550 man-nights) and 234 collections of the house-resting fauna were carried out from October 1982 to May 1984 in Brazzaville. A total of 19,531 Culicidae were captured, of which 1,893 were Anopheles, almost exclusively A. gambiae. An average sporozoite rate of 3.41% was found from dissection of 1,291 A. gambiae: one female A. moucheti was also found to be infected. Considerable differences in the intensity of transmission of malaria were observed in the different districts of the town. Whereas the inhabitants of Brazzaville received on average 22.5 infective bites per person per year, in reality this number varies according to the district, from over 100 infective bites per person per year, to less than one infective bite per person every three years. With the help of classical quantitative epidemiological models, the authors analyse here the over-all results, as well as those of two areas of the town, the first area characterized by a high anopheline density, and the second by the rarity of anopheles. PMID- 2901797 TI - Lymphokine-activated killer cell purging of leukemia cells from bone marrow prior to syngeneic transplantation. AB - We have studied the effect of using lymphokine-activated killer (LAK) cells as an in vitro means for eliminating leukemic cells from normal bone marrow prior to transplantation of experimental animals. Rat LAK cells exhibit broad cytolytic activity against a variety of hematopoietic neoplasms, but do not kill normal bone marrow cells or lectin-stimulated blasts. Bone marrow was harvested from normal Fischer 344 rats, combined with increasing numbers of CRNK-16 tumor cells, and then incubated with LAK cells. The BM/tumor/LAK mixture was then administered to untreated Fischer rats, and the ability of the LAK cells to purge the bone marrow of neoplastic cells and prevent the transmission of the leukemia to recipient animals monitored. Our results demonstrate that LAK cells are capable of efficiently purging the bone marrow of neoplastic cells. Treatment of the BM/tumor mixtures with LAK cells is associated with significant prolongation of survival in the higher tumor doses (10(5) tumor cells/recipient) and complete elimination of the tumor in a high percentage of recipients at lower tumor levels (10(3)-10(4) tumor cells/recipient). At levels of BM transfer comparable to that used in humans, there was no evidence of a failure of LAK-treated bone marrow to reconstitute lethally conditioned recipient animals. However, with lower numbers of BM cells, there was an increased mortality in animals receiving LAK-treated BM, suggesting a minimal inhibition of pluripotent hematopoietic stem cell function when suboptimal numbers of BM cells are used for reconstitution. These experiments demonstrate that LAk cells are capable of eliminating neoplastic cells in bone marrow without significant destruction of immature syngeneic stem cells. LAK cells display a broad range of cytolytic activity against hematopoietic and solid tissue tumors, and are therefore capable of eliminating small numbers of tumor cells from a wide variety of neoplastic diseases of the marrow. The ability to detect and eliminate malignant cells, without interfering with reconstitution with donor marrow, suggests that immune therapy with LAK cells can be a relatively simple and efficient method to purge bone marrow prior to autologous transplantation in patients following high-dose chemotherapy for neoplastic diseases. PMID- 2901798 TI - Pathogenesis of urinary tract infections: host susceptibility and bacterial virulence factors. PMID- 2901799 TI - [The effect of early visual deprivation on the synthesis of glutamic and aspartic acids in mitochondria of central structures of the visual analyzer in the dog]. AB - After 45 days visual deprivation synthesis via direct reductive amination and transamination of glutamic and aspartic acids was inhibited in mitochondria of dog visual cortex, colliculi anterioris and corpus geniculatum externus. Under conditions of long-term (90 days) visual deprivation synthesis of glutamic and aspartic acids was less effectively inhibited in mitochondria of the brain areas studied via the reductive amination and transamination, except of the aspartic acid synthesis by means of transamination, the rate of which was maintained at the level similar to the values observed after 45 days of visual deprivation. PMID- 2901800 TI - [Effect of pyrilene and temechin on central and pulmonary hemodynamics in the treatment of hemoptysis]. PMID- 2901801 TI - Spectrum of pheochromocytoma in the 131I-MIBG era. PMID- 2901802 TI - First workshop of the MRC AIDS-directed programme, 9-10 November 1987, Central Public Health Laboratory, Colindale, London, UK. PMID- 2901803 TI - [Fimbrial formation, antibiogram, plasmid content, lysotype and biotype of Salmonella]. PMID- 2901804 TI - Early expression of MCS2 (CD13) in the cytoplasm of blast cells from acute myeloid leukaemia. AB - The expression of two myeloid antigens identified by the monoclonal antibodies (McAb) MCS2 (CD13) and MY9 (CD33) was investigated in 136 cases of leukaemia. MCS2 was positive in blast cells of 78 of 88 (88.5%) and MY9 in 51 of 81 (64%) cases of acute myeloid leukaemia (AML) and chronic granulocytic leukaemia in myeloid blast crisis. One or other McAb, or both, were positive in all but 2 (2.3%) of these cases. MCS2 was more sensitive than MY9 to detect blasts of the myeloid lineage due to its most frequent reactivity in the cytoplasm of fixed cells by the immunoperoxidase (IP) technique compared with its membrane expression on cell suspensions by immunofluorescence (IF). MY9 was not suitable for tests on fixed cells. MCS2 was positive by IP but not by IF in 24% of AML, but the reverse was not observed. This suggests that the antigen detected by MCS2 is expressed in myeloblasts first in the cytoplasm and later on the cell membrane, pattern which is similar to that of the early antigens CD3 and CD22 in T and B lineage lymphoblasts, respectively. MCS2 was always positive in FAB types of AML-involving myeloblasts (M1-M4), including cases of undifferentiated morphology (M0), whilst MY9 was more frequently positive in monocytic leukaemia (M5). On the other hand, MCS2 was positive in 4 of 33 cases of acute lymphoblastic leukaemia and MY9 in 1. We conclude that both McAb, particularly MCS2, contribute to the better characterisation of myeloid leukaemias but that other tests are required to clarify the nature of the blasts when unexpected reactivities are observed. PMID- 2901805 TI - A study of the dipeptidylpeptidase IV activity in cat fungiform papillae: light and electron microscope histochemistry. AB - The present paper describes histochemical study of the dipeptidylpeptidase IV activity in the nerve structures of cat fungiform papillae at the light and electron microscope levels. The dipeptidylpeptidase IV activity was found in blood vessels and nerve bundles entering the connective tissue stroma of fungiform papillae. The taste buds exhibited a moderate staining for the dipeptidylpeptidase IV activity. Ultracytochemical findings revealed this enzyme as membrane-bound in the endothelium of blood vessels, in plasma membrane of the Schwann cells at the axon-Schwann cell interface as well as in the taste bud cells. A possible function of the dipeptidylpeptidase IV activity in the peripheral nerve structures is discussed in view of the ability of this enzyme to cleave the substance P to the minor fragments with inherent physiological roles. PMID- 2901806 TI - Beta-adrenoceptor blockade and anesthesia. PMID- 2901807 TI - Psychophysiological aspects of central fatigue. PMID- 2901808 TI - [Synthesis of higenamine derivatives and their open-ring analogs]. PMID- 2901809 TI - Oxidative metabolism in cultured astroglial cells from rat brain. AB - Growth, morphology, glutamine synthetase activity, cytochrome C oxidase activity and respiratory activity of rat brain cultures enriched in astrocytes were studied during four weeks in culture. Two different polarographic methods were used for measurement of respiratory activity: one newly developed perfusion method leaving the cellular monolayer morphologically intact and still attached to the culture dish, and one traditional stirring method involving the removal of cells from the culture vessel. Regardless of the method used, a stable respiratory activity was registrated throughout the four weeks of culturing. Also the cytochrome C oxidase activity remained unchanged. In perfusion all absolute values for respiration were found to be higher than those obtained with the stirring method. The use of the stirring technique resulted in a doubling of oxygen consumption upon succinate addition. No such effect was seen in perfusion. It can thus be concluded that the removal of cultured astrocytic cells from their substratum alters their respiratory activity and their response to added substrates. PMID- 2901810 TI - Postnatal development of gamma-GT activity in rat brain microvessels corresponds to capillary growth and differentiation. AB - It has been demonstrated histochemically that endothelial cells of the cerebral capillaries show a high activity in gamma-glutamyl transpeptidase (gamma-GT), an enzyme which takes part in the transfer of large neutral amino acids across the blood-brain barrier. Reports of the disappearance of enzyme activity in endothelial cells (EC) grown in culture suggest that the presence of astroglial cells (AG) is required for the expression of gamma-GT in these cells. The present study deals with the developmental changes in gamma-GT activity in capillaries of rat cerebral cortex during ontogenesis (i.e. on days 2, 7, 11, 14, 21 and 60 after birth). gamma-GT activity is determined by measuring the enzyme kinetics of the histochemical reaction on isolated brain capillaries using a flying spot microscope densitometer. Enzyme activity is expressed as an increase in relative optical density (at 500 nm) in arbitrary units/min/micron 2 during the 2 min immediately after initiating incubation and corresponds to the gamma-GT active area (in micron 2) of the capillary segment. During early postnatal development, a biphasic change of gamma-GT activity in capillaries of rat cerebral cortex is observed. The first phase (i.e. the postnatal period between the 2nd and 12th day) is characterized by a significant decrease in gamma-GT activity, which coincides with the onset of the rapid mitotic proliferation of cortical endothelial cells. During the second phase (i.e. the postnatal period between the 12th and 21st day), a fast increase in the gamma-GT activity can be measured. Then enzyme activity reaches the adult level between the 21st and 60th postnatal day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901811 TI - Disodium azodisalicylate and sulfasalazine. PMID- 2901812 TI - Isolated amebic appendicitis: a pathologic rarity. PMID- 2901813 TI - Regulation of corticotropin-releasing factor secretion in vitro by glucose. AB - The neurosecretory responses of the isolated rat hypothalamus were assessed in vitro. Rat hypothalamic blocks were incubated for 30 min in a N-2 hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered salt solution with 5.5 mM glucose (base-line collection period). The blocks were transferred to fresh buffer with a new concentration of glucose with or without various additions (test period); corticotropin-releasing factor (CRF) and other hormones in the media were determined by radioimmunoassay. CRF secretion was maximally increased to approximately 200% of base line at glucose concentrations less than 4 mM and decreased to 65% of base line at higher glucose concentrations. The increase in CRF secretion at low glucose (0.55 or 1.38 mM) was Ca2+ dependent and completely reversible. Hexamethonium, cyproheptadine, and atropine partially blocked the CRF response to 0.55 mM glucose. Glucose concentrations from 0 to 11 mM had no effect on the CRF response to 47.5 mM KCl. The inhibitory effects of high glucose were completely reversed by the addition of 2-deoxy-D-glucose (3-49 mM). Glucose levels did not alter secretion of either gonadotropin-releasing hormone or arginine vasopressin from hypothalamic blocks. The results suggest that the isolated rat hypothalamus is extremely sensitive to the level of glucose and that CRF is rapidly and reversibly secreted in response to slight reductions in glucose concentrations. These concentrations are consistent with those observed during moderate to severe hypoglycemia in vivo. The rise in glucocorticoids observed in vivo during hypoglycemia may result at least in part from the ability of the hypothalamus to directly sense glucose levels and promote secretion of CRF. PMID- 2901814 TI - Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles. AB - The regulation of glutamine synthetase expression by dexamethasone was studied in rat skeletal muscles. Daily administration of dexamethasone caused striking enhancement of glutamine synthetase activity in plantaris, soleus, and diaphragm muscles. Northern blot analysis revealed that the dexamethasone-mediated increase of glutamine synthetase activity was associated with dramatically increased levels of glutamine synthetase mRNA. Both glutamine synthetase activity and mRNA levels were significantly elevated in plantaris muscle at 0.5 mg.kg-1.day-1 of dexamethasone, a dose that approximates endogenous corticosteroid levels in animals under severe stress. Quantification of changes in glutamine synthetase mRNA on the basis of total mRNA (by oligo dT hybridization) also revealed a major increase in glutamine synthetase mRNA. Dexamethasone was without effect on beta tubulin mRNA levels, indicating that glutamine synthetase induction is not part of a global response to glucocorticoids. Dexamethasone treatment resulted in only an approximately 15% increase in glutamine synthetase activity in heart; there was no change in glutamine synthetase mRNA level in this tissue. Thus glucocorticoids regulate glutamine synthetase gene expression in rat skeletal muscles. PMID- 2901815 TI - Premedication with oral slow release morphine in dental anaesthesia. A comparison with temazepam. AB - Oral slow release morphine 30 mg and temazepam 30 mg given as premedication 2 hours before operation were compared in 62 patients who underwent extraction of four third molar teeth in a randomised double-blind trial. There was no significant difference in pre-operative sedation; the majority were mildly or moderately sedated. Patients in the morphine group woke up significantly faster and had significantly reduced requirements for analgesics after operation. PMID- 2901816 TI - Combined use of calcium-channel and beta-adrenergic blockers for the treatment of chronic stable angina. Rationale, efficacy, and adverse effects. AB - During the past decade, the therapy for stable angina pectoris has greatly expanded with the introduction of the calcium-channel blockers. Initially studied as monotherapy, these agents have been regularly used in combination with other antianginal medications, most notably the beta-adrenergic blockers. Although there are pharmacologic rationales for combining these agents, in daily practice, the major impetus for combination therapy is continuing angina during monotherapy. At least one well-conducted double-blind study was done to confirm that diltiazem, verapamil, and nifedipine each can markedly improve both subjective and objective measures of efficacy when used in combination with a beta-blocker. However, individual patient responses are of chief importance. Many persons do better with monotherapy than with combination treatment. The offsetting hemodynamic effects of nifedipine and a beta-blocker generally work well together; however, minor side effects are not infrequent. In the patient with underlying conduction system disease, this combination is clearly preferable. Diltiazem with a beta-blocker is usually well-tolerated, with a low incidence of adverse effects, similar to the experience with diltiazem monotherapy. Verapamil in conjunction with a beta-blocker warrants the greatest concern; approximately 10% to 15% of patients will have significant bradycardia, heart block, hypotension, or congestive failure. When these agents are used concurrently, reduced dosages, especially of the beta-blocker, will likely result in a lower incidence of adverse effects with maintained efficacy. PMID- 2901817 TI - Bronchoalveolar lymphocytosis in patients with tropical spastic paraparesis associated with human T-cell lymphotropic virus type 1 (HTLV-1). Clinical, immunologic, and cytologic studies. AB - STUDY OBJECTIVE: To determine the features of pulmonary involvement in patients with tropical spastic paraparesis associated with human T-cell lymphotropic virus type 1. DESIGN: Nonrandomized prospective case series. SETTING: Tertiary care units in two university medical centers. PATIENTS: Consecutive sample of 21 patients with tropical spastic paraparesis associated with human T-cell lymphotropic virus type 1 infection. INTERVENTIONS: Chest roentgenogram and bronchoalveolar lavage were done in all patients. Fifteen patients had pulmonary function tests. Alveolar T-lymphocyte subsets were analysed in 10 patients and thoracic computed tomographic scans were done in 10 patients. MEASUREMENTS AND MAIN RESULTS: All patients were free of clinical pulmonary symptoms and had normal chest roentgenograms. Thoracic computed tomographic scans were normal in 9 of 10 patients and showed mild interstitial pneumonitis in 1. Pulmonary function tests were within the normal range in 13 patients and showed a mild restrictive syndrome in 2. Eighteen patients had increased absolute numbers of alveolar lymphocytes (mean, 77 +/- 39 X 10(3) lymphocytes/mL; range, 13.5 X 10(3) to 259 X 10(3) lymphocytes/mL). Sixteen patients had percentages of alveolar lymphocytes higher than 20% of all alveolar cells (mean, 33.5 +/- 12.7; range, 9 to 69). In all 10 patients tested, 64.2% +/- 13.2% of alveolar lymphocytes were CD8+ cells. CONCLUSIONS: Excessive absolute numbers and percentages of alveolar lymphocytes were observed in 18 and 16 patients, respectively. Most alveolar lymphocytes were CD8+ cells. PMID- 2901819 TI - SMS 201-995, a somatostatin analogue, and diarrhea in the acquired immunodeficiency syndrome (AIDS) PMID- 2901818 TI - Hypertension, exercise, and beta-adrenergic blockade. AB - STUDY OBJECTIVE: To determine whether beta-adrenergic blocking agents affect exercise tolerance, exercise conditioning response, and blood pressure response to conditioning in hypertensive patients. DESIGN: Randomized, double-blinded, placebo-controlled trial with a 10-week exercise period. SETTING: Outpatient, monitored exercise program at a community-based, university-sponsored cardiac rehabilitation facility. PATIENTS: Thirty adults with mean resting blood pressure of 145 mm Hg or greater (systolic), 95 mm Hg or greater (diastolic), or a combined systolic and diastolic pressure of 140/90 mm Hg or greater. Mean systolic pressure of 170 mm Hg or more or mean diastolic pressure of 105 mm Hg or more was exclusionary. Mean blood pressure was 145/95 mm Hg; mean age was 46.5 years. INTERVENTION: The beta-1-nonselective blocker was propranolol, 80 mg twice daily. The beta-1-selective blocker was metoprolol, 100 mg twice daily, compared with placebo. All patients did exercise conditioning consisting of 40 sessions of aerobic exercise with heart rate monitoring. MEASUREMENTS AND MAIN RESULTS: Resting systolic blood pressure measured without drug therapy was lowered markedly after exercise conditioning on placebo (146 to 135 mm Hg) and on metoprolol (144 to 133 mm Hg) (P less than 0.05), but not on propranolol (no change). Acutely, propranolol decreased both maximal oxygen consumption (VO2max) and exercise duration compared with metoprolol and placebo. Chronically, VO2max increased 24% (95% CI, 8 to 40) in response to training on placebo and 8% on metoprolol (95% CI, 3 to 14); it did not increase on propranolol (95% CI, -10 to 15). CONCLUSIONS: If an exercise program is to be recommended as an adjunct to pharmacologic beta-blockade for hypertension, blood-pressure-lowering effects are preserved and exercise capacity is less affected with a beta-1-selective agent than with a beta-1-nonselective agent. Antihypertensive medications may be avoided altogether for selected patients who sustain an aerobic exercise program. PMID- 2901820 TI - [Central neurotransmitters and control of specific appetite for the macronutrients]. AB - Studies of brain monoamines and neuropeptides have provided extensive evidence in support of their role in the control of food intake, meal patterns and appetite for specific macronutrients. In this process, the medial and lateral portions of the hypothalamus have a critical responsibility in balancing signals for hunger and satiety. Via its rich and biologically active neurotransmitter substances, the hypothalamus monitors and integrates the complex sensory and metabolic input concerning the nutritional status of the organism and transduces this information into appropriate quantitative and qualitative adjustments in food intake. The specific neurotransmitters for which there is the most extensive evidence for a physiological function include the eating-stimulatory substances norepinephrine, opioid peptides, pancreatic polypeptides, galanin and gamma-aminobutyric acid; and the eating-inhibitory substances dopamine, epinephrine, serotonin and several gut-brain peptides. From biochemical, pharmacological and anatomical studies, hypotheses have been generated to explain the role of these various monoamines and neuropeptides in controlling total energy intake, in determining the amount and pattern of macronutrient selection, and in maintaining normal energy and nutrient stores under dynamic conditions within the external environment. PMID- 2901821 TI - [New treatments of hemorrhagic rectocolitis]. AB - The treatment of ulcerative colitis has benefited from the development of new molecules (azo-disalicylates) or new galenic forms (Pentasa, Azacol...) permitting, via oral administration, to supply the colon with 5-aminosalicylic acid without the sulfapyridine with which it was combined in salazosulfapyridine and was responsible for most side effects. Pentasa and steroids which are moderately absorbed by the colonic mucosa (tixocortol pivalate, prednisolone metasulfabenzoate may also be used un an enema form or, for some, in ointment form, to treat mild attacks in the distal forms of the disease. PMID- 2901822 TI - Investigation on cerebrospinal fluid opioids and neurotransmitters related to spinal cord stimulation. AB - The purpose of this study was to assess the biochemical mechanisms underlying spinal cord stimulation (SCS). Seventeen patients with chronic pain were investigated by measuring cerebrospinal fluid concentrations of endogenous opioids and biogenic amines before and during dorsal column stimulation. Basal cerebrospinal fluid beta-endorphin levels were below the normal range. No significant change of norepinephrine, epinephrine, dopamine, beta-endorphin, beta lipotropin, or adrenocorticotropic hormone levels were found after SCS. A 50% increase of cerebrospinal beta-endorphin and beta-lipotropin levels occurred in 6 out of 16 patients, namely those where SCS gave the major pain relief. These data confirm the derangement of the endogenous opioid system in chronic pain conditions and suggest that the beta-endorphin response to SCS could have clinical value in predicting the success of treatment. PMID- 2901823 TI - The amino acid sequence of bovine thymus prothymosin alpha. AB - Prothymosin alpha has been purified from calf thymus and its amino acid sequence determined. It contains 109 amino acid residues and closely resembles human prothymosin alpha, with only two substitutions, glutamic acid for aspartic acid at position 31 and alanine for serine at position 83. This is in contrast to six differences between rat and bovine prothymosins, including four substitutions and two deletions. The structural similarity of the bovine and human polypeptides makes the former a good candidate for studies on the evaluation of the biological activities of prothymosin alpha in human systems. PMID- 2901824 TI - Effect of SM-2470, a newly synthetized alpha 1-adrenoceptor antagonist, on sympathetic nerve activity in anesthetized rats. AB - The newly synthetized alpha 1-adrenoceptor antagonist, SM-2470 (4-amino-2-[4 (bicyclo(2,2,2)oct-2-ene-5-carbonyl)-1-piperazinyl]-6,7- dimethoxyquinazoline hydrochloride), is a prazosin-like quinazoline derivative. The present study was undertaken to elucidate the effect of SM-2470 on sympathetic nerve activity and baroreceptor afferent nerve activity in anesthetized rats. Intravenous administration of SM-2470 (10, 30 and 100 micrograms/kg) produced a dose dependent reduction of mean arterial pressure without any significant change in heart rate. SM-2470 caused decreases in both renal and cardiac sympathetic nerve activity along with this hypotension. Preganglionic adrenal nerve activity and aortic depressor nerve activity were also decreased by SM-2470. When equi hypotensive doses of SM-2470 and clonidine were compared, the sympathoinhibitory potency of SM-2470 was less than that of the centrally acting antihypertensive drug, clonidine. Pretreatment with SM-2470 (30 micrograms/kg, i.v.) shifted the methoxamine-induced pressor response curve to the right. These findings suggest that SM-2470 may possess a central sympathoinhibitory action. This central action may play a role in its anti-tachycardic effect and may be substantially responsible for the hypotensive action. PMID- 2901825 TI - Inhibition via muscarinic M-1 receptor stimulation of TRH-induced prolactin release in estrogen-primed rats. AB - The cholinergic mechanism involved in the regulation of prolactin secretion induced by thyrotropin-releasing hormone (TRH) in estrogen-primed male rats was investigated. Intraperitoneal injections of pharmacological doses of TRH (20 mg/kg), MK-771 (2 mg/kg) and DN-1417 (10 mg/kg) increased serum prolactin levels in estrogen-primed male rats, but not in nonprimed male rats. This increase was reduced by pilocarpine, a muscarinic M-1 receptor agonist, but not by carbachol, a M-2 receptor agonist. Pirenzepine, a peripheral M-1 receptor antagonist, did not affect TRH-induced prolactin release, but antagonized the inhibitory effect of pilocarpine. The results indicate that TRH and TRH analogues increase prolactin secretion in the estrogen-primed male rats and that a stimulation of muscarinic M-1 receptors exerts an inhibitory effect on the prolactin release induced by TRH in the estrogen primed male rats. PMID- 2901826 TI - Pharmacological activity of novel alkylsulfonylaryl-1-substituted-1,4 benzodiazepine derivatives. AB - A series of 1-alkylsulfonylaryl-1,4-benzodiazepine derivatives were synthesized and assayed for their pharmacological profile. All the compounds tested exhibited a competitive antagonism of 3H-diazepam binding in cerebellum, cerebrum and submaxillary gland. Compound II (rec. INN tolufazepam) had a Ki of 12.7 nM in cerebrum and 400 nM in the submaxillary gland. It was very potent in preventing convulsions elicited by pentylenetetrazol (ED50 p.o.: 16.5 and ED50 i.v.: 20 mg/kg). This anticonvulsant action was suppressed by previous administration of Ro 15-1788. Compound II was also active in inhibiting suppressive behaviour in the test of Vogel. This compound has a relative low hypnogenic activity as well as a low potency to produce motor incoordination. Our results show that tolufazepam has a potential clinical usefulness. PMID- 2901827 TI - Antisomatostatin IgG in major depressive disorder. A preliminary study with implications for an autoimmune mechanism of depression. AB - IgG reactive with somatostatin 1-14 was identified in human plasma by enzyme linked immunosorbent assay. From a sample of 25 subjects, six (60%) of ten individuals with major depressive disorder demonstrated antibody reactive with somatostatin 1-14, in contrast to one (7%) of 15 controls. Overall, antisomatostatin reactivity was significantly higher in patients with major depressive disorder (0.233 +/- 0.177) than in the normal volunteers (0.084 +/- 0.039; t = 3.18, P less than .01). Antisomatostatin IgG was isolated by affinity chromatography. The recognition site for somatostatin was retained by F(ab)'2 fragments. Although there has been little previous exploration of the existence of antibodies to endogenous neuropeptides, such antibodies could prove of relevance to neuropsychiatric and other human disorders. PMID- 2901828 TI - Hospital play specialists. PMID- 2901829 TI - Enkephalin is liberated from metorphamide and dynorphin A1-8 by endo oligopeptidase A, but not by metalloendopeptidase EC 3.4.24.15. AB - It has been previously reported that both the cysteinyl-endo-oligopeptidase A and the metalloendopeptidase EC 3.4.24.15 are able to generate enkephalin from a number of enkephalin-containing peptides, including dynorphin A1-8. The present study shows that only endo-oligopeptidase A is able to generate [Leu5]enkephalin and [Met5]enkephalin from dynorphin A1-8 and from metorphamide respectively. It is also shown that endo-oligopeptidase A neither hydrolyses the specific EC 3.4.24.15 substrate alpha-N-benzoyl-Gly-Ala-Ala-Phe p-aminobenzoate, nor is inhibited by the specific EC 3.4.24.15 inhibitor N-[1(RS)-carboxy-2-phenylethyl] alpha-Ala-Ala-Phe p-aminobenzoate. PMID- 2901830 TI - Evidence of functional alpha 2-adrenergic receptors in adult-rat adipocytes by using the agonist UK 14304. AB - The aim of this study was to re-assess whether alpha 2-adrenergic receptors were present in rat adipocytes, by using UK 14304, a new and very selective alpha 2 agonist. The following observations demonstrate the presence of functional alpha 2-adrenoceptors in rat adipocytes. (1) Adipocyte lipolysis was dose-dependently inhibited by UK 14304 (maximal effect 80% at 1 microM-UK 14304, 45% at 10 microM UK 14304, under basal or theophylline-stimulated conditions respectively). (2) UK 14304 bound specifically to purified plasma membranes, with Bmax. = 744 fmol/mg of protein and KD = 9 nM. (3) The effect of UK 14304 was suppressed by alpha 2 antagonists. (4) Adrenaline inhibited lipolysis upon beta-adrenergic blockade (propranolol). (5) The anti-lipolytic effect of UK 14304 was modulated by the age of the rats. PMID- 2901831 TI - A collagen-binding glycoprotein on the surface of mouse fibroblasts is identified as dipeptidyl peptidase IV. AB - A dipeptidyl aminopeptidase (DPP) was detected in plasma membranes from normal (3T3) and transformed (3T12) mouse fibroblasts. This enzyme was active in cleaving the prolyl bond in the synthetic dipeptide nitroanilide Gly-Pro-NH-Np, which is a specific substrate for DPP IV (Km 0.63 mM and Vmax 6.1 nmol/min per mg at pH 6.0 and 37 degrees C). However, it did not degrade Pro-NH-Np or other dipeptide nitroanilides such as Gly-Arg-NH-Np or Val-Ala-NH-Np. The enzyme was totally inhibited by di-isopropyl phosphorofluoridate (Pri2-P-F) and by phenylmethanesulphonyl fluoride, indicating a serine catalytic site for the proteinase. DPP IV is a glycoprotein that specifically recognized immobilized gelatin and type I collagen. Upon molecular exclusion chromatography, the proteinase exhibited an apparent Mr of 100,000. SDS/polyacrylamide-gel electrophoresis under non-reducing and reducing conditions revealed that the [3H]Pri2-P-protein was exclusively represented by a polypeptide of Mr 55,000. This suggested that DPP IV consists of two non-covalently linked 55,000-Mr subunits. Fibroblast adhesion to native or denatured collagen was significantly inhibited by the two dipeptide inhibitors of DPP IV, Gly-Pro-Ala and Ala-Pro-Gly, but not by the peptides Gly-Pro and Gly-Gly-Gly, which are not inhibitors of the proteinase. Moreover, preliminary fractionation of DPP IV by molecular exclusion chromatography and affinity chromatography indicated that this material was active in disrupting cell adhesion to collagens. Taken together, the above data suggest that a fibroblast membrane-associated collagen-binding glycoprotein, DPP IV, may play a role in cell attachment to collagen. PMID- 2901832 TI - Retinoic acid-induced modulation of rat liver transglutaminase and total polyamines in vivo. AB - The effect of a single intraperitoneal injection of retinoic acid on liver transglutaminase (EC 2.3.2.13) activity and total putrescine, spermidine and spermine was studied. The results demonstrate that: (1) transglutaminase activity is increased over control values as early as 4-6 h after treatment, reaching a maximum (2-fold increase) at 12 h and returning to control values at 36 h; (2) the retinoic acid-induced form of enzyme is the soluble tissue transglutaminase; (3) actinomycin D treatment does not completely inhibit the early (6 h) increase of activity, while suppressing that at 12 h; (4) the immunoassay of the soluble transglutaminase shows that, 6 h after treatment, there is no increase in the protein, whereas at 12 and 24 h a significant increase is observed; (5) putrescine, but not spermidine and spermine, increases (5-7-fold) 6 and 18 h after the retinoic acid treatment. The possibility also that the expression of soluble transglutaminase is modulated in vivo by retinoic acid and the relationship to polyamine levels are discussed. PMID- 2901833 TI - Cloning and characterization of an alpha 1-antitrypsin like gene 12 KB downstream of the genuine alpha 1-antitrypsin gene. AB - Cosmid clones containing alpha 1-antitrypsin (alpha 1AT) gene sequences were observed to contain alpha 1AT-like sequences approximately 12 kb downstream of the authentic alpha 1AT gene. Restriction mapping suggested the alpha 1AT-like gene lacks promoter sequences. Cosmid clones from one library contained a truncated alpha 1AT-like gene with a deletion encompassing 1745 bp, including the whole exon IV and part of exon V. Sequencing of exon II of this truncated gene revealed a nucleotide homology of 76% but included critical mutations in the start codon (ATG - greater than ATA) and the 3' exon-intron junction. These results strongly suggest that the truncated alpha 1AT-like gene is a pseudogene, which is present at a frequency of 0.30 in the Dutch population. PMID- 2901834 TI - Reduction to homozygosity at the SIS/PDGF-2 locus in human mesenchymal tumors. AB - Enhanced expression of the human SIS/PDGF-2 gene has been reported in a number of human cell lines, sarcomas, and glioblastomas. We have analyzed the SIS/PDGF-2 gene for structural alterations in fresh human tumors. DNA samples from 79 patients with solid tumors (63 mesenchymal tumors, 12 lung carcinomas, 4 breast carcinomas) were examined and compared with DNA samples from 50 leukemia patients and 14 unrelated individuals without malignant neoplasms. When DNA samples were digested with a HindIII restriction endonuclease, Southern blot analysis demonstrated two distinct bands (21kb and 18kb) after hybridization to the SIS/PDGF-2 gene probe. A pedigree analysis of a 43-member family indicated that these allelic variants segregated in a Mendelian fashion. There was, however, tumor specific allele loss in 18% of the mesenchymal tumors analyzed, which may indicate a common etiology for this tumor type. PMID- 2901835 TI - Expression of a P-glycoprotein gene is inducible in a multidrug-resistant human leukemia cell line. AB - A human T lymphoblastoid CCRF-CEM cell line exhibiting cross resistance to a variety of drugs was selected with increasing doses of actinomycin D. A subline, designated CCRF ACTD400+, was permanently cultured in the presence of 400 ng/ml Actinomycin D for several months. Using a fragment of the human mdr1 cDNA we found high expression of a 5 kb mRNA species which was not detectable in the sensitive parental CCRF-CEM cell line. The extent of the mdr-mRNA expression in resistant cells, however, depended on the presence or absence of actinomycin D in the culture medium: when the inhibitor was omitted, the expression decreased to about 60% after one month. In reverse, the steady state level of the P glycoprotein mRNA increased about 2.5-fold within 72 h after the original dose of the drug was added again. In further experiments we recorded the actinomycin D or adriamycin dose response curves of the variously treated sublines by evaluation of [3H]uridine or [3H]thymidine incorporation, respectively, into acid insoluble material. Consistently, the drug sensitivity of the respective macromolecular synthesis was found to decrease with increasing mdr-mRNA levels. PMID- 2901836 TI - Rapid detoxification of infused ammonium by the anesthetized rat. AB - Anaesthetized rats were given an i.v. overload of 200 mmoles of ammonium acetate. Plasma ammonium levels were not altered for up to 20 minutes after the end of the infusion. The load of ammonium, however, increased the overall non-protein nitrogen content of circulating plasma, as for the increase in urea and amino acids (alanine, phenylalanine, aspartate + asparagine and glutamate + glutamine). The activities of glutamine synthetase was found increased in liver, muscle and kidney; and glutamate dehydrogenase increased in liver and decreased in muscle and kidney. Adenylate deaminase decreased in all the studied tissues. The fast enzyme and plasma metabolite adaptations to ammonium overload were all in the sense of favoring the incorporation of ammonium into amino acids (later into urea) as well as to avoid their deamination, thus effectively removing the excess ammonium from the bloodstream. PMID- 2901837 TI - Toxicity of polycyclic aromatic hydrocarbons. VI. Effects of 1-nitropyrene on serum enzyme levels in rats, and protection against it by beta-naphthoflavone and dimethyl sulfoxide. AB - Male Sprague-Dawley rats were pretreated i.p. with corn oil or DMSO (1.5 ml/kg/day), or with beta-naphthoflavone (BNF, 40 mg/kg/day) in corn oil or DMSO for 3 days. 1-Nitropyrene (1-NP, 150 mg/kg) in DMSO was injected i.p. 24 hr after pretreatment. A significant increase in the levels of several serum enzymes was seen in rats pretreated with corn oil alone 24 hr after 1-NP injection. The increase in enzyme activities was significantly reduced by a 3-day pretreatment with DMSO or BNF. PMID- 2901838 TI - Toxicity of aromatic hydrocarbons. VII. Hepatotoxicity of 9-nitrophenanthrene, and protection against it by beta-naphthoflavone. AB - Male Sprague-Dawley rats were treated with a single i.p. injection of DMSO (3.0 ml/kg) or 9-nitrophenanthrene (9-NP, mg/kg) in DMSO. 9-NP produced a significant elevation of serum aspartate aminotransferase, alanine aminotransferase, sorbitol dehydrogenase, and gamma-glutamyl transpeptidase (GGTP) levels relative to DMSO injected rats 24 hr after injection. With the exception of GGTP, the increase in enzyme activities induced by 9-NP was significantly reduced by a 3-day pretreatment with beta-naphthoflavone (BNF; 40 mg/kg/day) in DMSO. The effect of 9-NP on GGTP levels was enhanced by BNF pretreatment. PMID- 2901839 TI - Sulfasalazine in the treatment of ankylosing spondylitis. A twenty-six-week, placebo-controlled clinical trial. AB - Eighty-five patients with active ankylosing spondylitis (AS) were randomized to receive either sulfasalazine (less than or equal to 3 gm/day, mean 2.5) or placebo for 26 weeks. There was a statistically significant improvement, compared with baseline, in most of the clinical variables in patients receiving the active drug. Laboratory parameters (erythrocyte sedimentation rate, C-reactive protein, IgG, IgM, and IgA) also improved during the active treatment, suggesting a beneficial effect of sulfasalazine on AS. At the end of the treatment, significant differences between the sulfasalazine and placebo groups were observed in morning stiffness, chest expansion, erythrocyte sedimentation rate, and in all immunoglobulin classes. Two patients in each treatment group discontinued the trial because of side effects. Enteric-coated sulfasalazine seemed to be effective and well tolerated in patients with active AS. PMID- 2901840 TI - The diagnosis of polyarteritis nodosa. I. A literature-based decision analysis approach. AB - We investigated diagnostic testing in polyarteritis nodosa (PAN) by calculating, from published data, the sensitivity and specificity of visceral angiography and muscle, nerve, testicle, kidney, and liver biopsy. Test sequence strategies were constructed by Bayesian inference using a computer program written for this purpose. Test sequences were compared with an aggressive strategy consisting of repeated tests until there was a positive finding or until the available tests were exhausted, and a conservative strategy consisting of 1 biopsy procedure plus angiography. The Bayesian analysis agreed most closely with the conservative approach for most prior probabilities (degree of suspicion) that a patient had PAN. The aggressive strategy had an overall sensitivity of 90% and specificity of 91%, whereas the conservative strategy was 85% sensitive and 96% specific. Furthermore, the aggressive strategy was more costly ($2,986 versus $1,961) and had a higher rate of morbidity (3.8 versus 2.7 days of hospitalization per patient evaluated) than did the conservative strategy. The mortality rates of both strategies were equivalent (approximately 0.05 deaths per hundred patients evaluated). The per-case cost of diagnosis increased as prevalence decreased, and at 10% prevalence, the aggressive strategy cost more than $17,000 per case diagnosed. Sensitivity analysis revealed that the strategies were moderately affected by the test characteristics, within reasonable assumptions, but that the differences in conservative and aggressive approaches remained. Thus, our analysis based on available data and the assumption of test independence suggests that the preferred diagnostic evaluation of patients with symptoms suggestive of PAN consists, in most cases, of a single biopsy procedure, with angiographic evaluation if necessary. PMID- 2901841 TI - The diagnosis of polyarteritis nodosa. II. Empirical verification of a decision analysis model. AB - We evaluated our literature-based estimates of diagnostic test characteristics and aggressive and conservative strategies for the diagnosis of polyarteritis nodosa (PAN) by reviewing 1980 through 1985 data from the University of Chicago Medical Center, Michael Reese Hospital, and Northwestern University Medical School. Test specificity was calculated by reviewing pathology and radiology reports on all relevant procedures done at the University of Chicago Medical Center in 1984 and 1985. There were no reports of false-positive findings (including angiography); thus, test specificity was 100% for muscle, nerve, kidney, liver, and testicular biopsy, which was comparable with our literature based estimate of 97%. Test sensitivity was based on the 18 confirmed cases of PAN from the 3 institutions and was similar to that in published reports, ranging from 0% for liver biopsy to 100% for visceral angiography. Review of each case for diagnostic test sequence showed an average of 2 diagnostic procedures to confirm the diagnosis (range 1-6). Eight of 18 patients were evaluated according to the conservative strategy we proposed from our literature-based decision analysis approach. No patient was evaluated with the aggressive strategy, although 1 patient had 6 invasive procedures. Of the remaining 10 patients, 9 represented cases that might have been confirmed had the conservative approach been used, and if it had been used, 6 patients would have had the diagnosis confirmed. Thus, the minimum sensitivity of our conservative strategy is 78%, although based on these data, it could be as high as 100%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901842 TI - Lymphocyte subset T4/T8 ratio in systemic lupus erythematosus: correlation with disease activity, laboratory abnormalities and treatment. AB - Lymphocyte subsets were studied in forty-nine patients with SLE using monoclonal antibodies and flow cytometry. A decrease in T4+ reactive cells (helper/inducer) was the most frequent observation. Decreased T4/T8 ratios were seen in patients with increasing clinically active disease, patients with positive anti-DS-DNA, positive anti-RNP antibodies and patients with low CH50 activity. However, low T4/T8 ratios were seen in patients with negative anti-Sm. Low T4/T8 ratios were also observed in patients taking prednisone at more than 10 mg/day and in patients treated with immunosuppressive drugs. PMID- 2901843 TI - The effect of pre-operative beta-blockade on the infusion requirements of atracurium during hypothermic cardiopulmonary bypass. A study using train-of-four electromyography. PMID- 2901844 TI - Parasitic load increases and myocardial inflammation decreases in Trypanosoma cruzi-infected mice after inactivation of helper T cells. AB - In order to characterize the role played by CD4+ T lymphocytes in the immunopathology of acute Trypanosoma cruzi infection, we compared the numbers of blood and tissue parasites and the heart inflammatory reaction in normal and anti CD4 antibody-treated C3H mice. Treatment of mice with anti-CD4 mAb during acute infection markedly inhibited T-helper-cell-dependent activities, as measured by peritoneal macrophage activation and immunoglobulin secretion by splenic B lymphocytes. After in vivo inactivation of helper T cells, the number of blood and tissue parasites significantly increased, while the inflammatory cellular infiltrates of heart muscles diminished. Our results indicate that CD4+ T lymphocytes play a dual role in the immunopathology of acute experimental Chagas' disease. PMID- 2901845 TI - In vivo anti-tumour activity of recombinant human tumour necrosis factor-alpha against Meth-A sarcoma requires L3T4-positive T cells. PMID- 2901846 TI - Reduced redox potential during growth of some gram-negative bacteria. Effect on the biochemical and physicochemical surface properties and phagocytosis by polymorphonuclear leukocytes. AB - When cultivated at reduced redox potential the physico-chemical surface properties were altered in strains of E. coli, Salmonella and Yersinia bacteria. In particular, strains which showed hydrophilic surface properties under normal aerobic cultivation became more hydrophobic when exposed to anaerobic conditions (e.g. E. coli K12, E. coli K12D21, E. coli K12D22, S. minnesota S99, S. typhimurium 395MS, S. braenderup 2828 and Yersinia enterocolitica). Moreover, there were qualitative as well as quantitative differences in the protein profiles of whole bacterial lysates and membrane preparations analysed in SDS PAGE. There were no qualitative differences in the lipopolysaccharide (LPS) bands. However, when E. coli K12D22 were cultivated aerobically, remarkably more high molecular temperature-sensitive (70 degrees C for 45 min) carbohydrate material was produced (weight about 360 KD and 660 KD). Interaction between polymorphonuclear leukocytes (PMNL) and the E. coli K12D22 strain, measured as chemiluminescence, showed that the anaerobically cultivated bacteria induced a chemiluminescence that was mainly of intracellular origin, while the aerobically cultivated induced an extracellular response. Phagocytosis and killing-studies showed that only anaerobically-grown E. coli were effectively inactivated by the PMNL. PMID- 2901847 TI - Health beliefs and behaviors of physician assistants in Texas: implications for practice and education. AB - Concern has been expressed over how the volume and effectiveness of physicians' practices relative to prevention can be increased. While a review of the health care services provided by physician assistants in medical practices indicated an emphasis on health education and patient counseling, there has existed an absence of data regarding their beliefs and practices in the area of health promotion. Based upon an analysis of self-reported data from 256 respondents (89%) of a random sample (n = 289) of the 870 physician assistants in Texas, it appears that physician assistants perceive themselves as having a role in health promotion, are generally satisfied with their preventive health care role, view health promotion activities as being more important in the future, and disagree with the idea that health promotion would not be well received by patients. They routinely gather information on health behaviors and discuss or recommend ways to reduce at risk behavior. Furthermore, while expressing certainty about their knowledge and skills to educate and influence individuals to change certain risk behaviors, physician assistants indicate less certainty about patient follow-through when it relates to such activities as smoking, drinking, and the use of illicit drugs. Considering the perceived challenge and the view that health promotion will become an even larger component of the physician assistant's future role, these findings suggest a need for additional skills training to better assist patients to modify their more complex health risk behaviors. PMID- 2901848 TI - Transluminal catheter angioplasty of abdominal aorta in Takayasu's arteritis. AB - Nine patients with Takayasu's arteritis and a long stenotic segment of the abdominal aorta were treated by percutaneous transluminal angioplasty (PTA). Intermittent claudication disappeared in six of seven cases, the femoral pulse reappeared in all five; ankle/arm indices increased in seven cases; elevated blood pressure normalized in seven of eight cases. Seven patients were followed for 3 to 28 months. They were all free of symptoms from the lower extremities. In three patients with or without renal artery stenosis and with hypertension, the blood pressure decreased after PTA of the abdominal aorta only. PTA may be a valuable treatment in Takayasu's arteritis and stenosis of the abdominal aorta. PMID- 2901850 TI - Growth inhibition and induction of phenotypic alterations in MCF-7 breast cancer cells by an IMP dehydrogenase inhibitor. PMID- 2901849 TI - Induction of peroxisome proliferation and hepatic tumours in C57BL/6N mice by ciprofibrate, a hypolipidaemic compound. AB - The hepatic effects of ciprofibrate, a potent peroxisome proliferator, were evaluated in male C57BL/6N mice, a mouse strain with very low incidence of spontaneous liver tumour development. Dietary feeding of ciprofibrate (0.0125% or 0.025% w/w) for 2 weeks resulted in a marked proliferation of peroxisomes (9-fold increase) and several-fold increase (8- to 10-fold) in the activity of peroxisomal beta-oxidation enzymes. Feeding ciprofibrate at 0.025% concentration for 15 months followed by a 0.0125% for 6 months led to the development of hepatic adenomas in 8/14 (57%) and hepatocellular carcinomas (HCC) in 3/14 (21%) mice. In mice given 0.0125% ciprofibrate for 18 months 5 of 8 (62%) and 3 of 8 (37%) developed adenomas and HCC respectively. Similar to the findings observed in rats, both the adenomas and HCC were negative for gamma glutamyltranspeptidase. These results in C57BL/6N mice of hepatocarcinogenic effect of ciprofibrate, a non-genotoxic chemical, indicate that peroxisome proliferation can be used as a reliable parameter to evaluate the carcinogenicity of hypolipidaemic compounds. PMID- 2901851 TI - Identification of the site of acetyl-S-enzyme formation on avian liver mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase. AB - Avian liver mitochondrial hydroxymethylglutaryl-CoA synthase contains an active site cysteine involved in forming the labile acetyl-S-enzyme intermediate. Identification of and assignment of function to this cysteine have been accomplished by use of an experimental strategy that relies upon generation and rapid purification of the S-acetylcysteine-containing active-site peptide under mildly acidic conditions that stabilize the thioester adduct. Automated Edman degradation techniques indicate the peptide's sequence to be Arg-Glu-Ser-Gly-Asn Thr-Asp-Val-Glu-Gly-Ile-Asp-Thr-Thr-Asn-Ala-Cys-Tyr. The acetylated cysteine corresponds to position 129 in the sequence deduced from cDNA data for the hamster cytosolic enzyme [Gil, G., Goldstein, J.L., Slaughter, C.A., & Brown, M.S. (1986) J. Biol. Chem. 261, 3710-3716]. The acetyl-peptide sequence overlaps that reported for a tryptic peptide that contains a cysteine targeted by the affinity label 3-chloropropionyl-CoA [Miziorko, H. M., & Behnke, C. E. (1985) J. Biol. Chem. 260, 13513-13516]. Thus, availability of these structural data allows unambiguous assignment of the acetylation site on the protein as well as a refinement of the mechanism explaining the previously observed affinity labeling of the enzyme. PMID- 2901852 TI - Interaction of an N-methylated polyamine analogue, hexamethonium(2+), with NaDNA: quantitative 14N and 23Na NMR relaxation rate studies of the cation-exchange process. AB - The interactions of the divalent hexamethonium (Hex2+) cation with double-helical calf thymus DNA are investigated by means of 14N NMR and, indirectly, by means of 23Na NMR. During a titration of NaDNA with HexBr2, the displacement of Na+ from DNA by Hex2+ is monitored by concurrent measurements of the Lorentzian 14N signals and the bi-Lorentzian 23Na signals. The variations in the quadrupolar relaxation rates of 14N and 23Na are analyzed according to a simple two-state model for the competition between Hex2+ and Na+ associated with DNA. From this analysis parameters characterizing the exchange process are evaluated, and the following conclusions are drawn: (1) The association of one Hex2+ displaces 1.7 2.0 sodium ions from the vicinity of the DNA. (2) Cation accumulation near DNA neutralizes approximately half of the phosphate charge at all points in the titration. (3) The exchange coefficient characterizing the displacement of Na+ by Hex2+ is of the same order of magnitude as the exchange coefficients determined by NMR for other divalent cations such as Mg2+ and putrescine. These findings imply that the interaction of Hex2+ with DNA is primarily electrostatic in character. The transverse and longitudinal relaxation rates observed for 14N are analyzed under the assumption that the quadrupolar relaxation processes of 14N in Hex2+ associated with DNA can be characterized by a single-exponential correlation function with correlation time tau NB. The resulting value of tau NB, 7.8 +/- 0.8 ns, is 3 orders of magnitude greater than that estimated for Hex2+ in the absence of DNA and is only 3-4 times greater than correlation times reported for 23Na and other quadrupolar cations near DNA. These comparisons indicate that the observed enhancements in the relaxation rates of 14N are due mainly to slowing of the motions that modulate its quadrupolar interactions in Hex2+ near DNA. The magnitudes of tau NB and of the quadrupolar coupling constant of Hex2+ associated with DNA are consistent with the conclusion that this association is primarily electrostatic. PMID- 2901854 TI - Cation dependence of opioid receptor binding supports theory on membrane-mediated receptor selectivity. AB - A quantitative analysis of the binding of dynorphin A-(1-9)-nonapeptide to the opioid Kappa-receptors of the guinea pig cerebellum [Paterson et al. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 6216-6220] shows that changes in electrostatic surface accumulation of the ligand fully account for the observed suppression of binding by a series of univalent and divalent salts. Binding to mu- and delta receptors, on the other hand, is subject to additional ion-specific effects. These observations support the membrane locations for the receptor sites proposed by the "membrane compartments" theory for opioid receptor selection. PMID- 2901853 TI - Binding of nucleotides to an extramitochondrial acetyl-CoA hydrolase from rat liver. AB - Cold labile extramitochondrial acetyl-CoA hydrolase (dimeric form) purified from rat liver was activated by various nucleoside triphosphates and inhibited by various nucleoside diphosphates. Activation of acetyl-CoA hydrolase by ATP was inhibited by a low concentration of ADP (Ki congruent to 6.8 microM) or a high concentration of AMP (Ki congruent to 2.3 mM). ADP and AMP were competitive inhibitors of ATP. A Scatchard plot of the binding of ATP to acetyl-CoA hydrolase (dimer) at room temperature gave a value of 25 microM for the dissociation constant with at least 2 binding sites/mol of dimer. Cold-treated monomeric enzyme also associated with ATP-agarose, suggesting that the monomeric form of the enzyme also has a nucleotide binding site(s), probably at least 1 binding site/mol of monomer. Phenylglyoxal or 2,3-butanedione, both of which modify arginyl residues of protein, inactivated acetyl-CoA hydrolase. ATP (an activator) greatly protected acetyl-CoA hydrolase from inactivation by these reagents, while ADP (an inhibitor) greatly (a substratelike, competitive inhibitor), and CoASH (a product) were less effective. However, addition of ADP plus valeryl-CoA (or CoASH) effectively prevented the inactivation by 2,3-butanedione, but that is not the case for phenylglyoxal. These results suggest that one or more arginyl residues are involved in the nucleotide binding site of extramitochondrial acetyl CoA hydrolase and that their nucleotide binding sites locate near the substrate binding site. PMID- 2901855 TI - Relationship of tightly bound ADP and ATP to control and catalysis by chloroplast ATP synthase. AB - Whether the tightly bound ADP that can cause a pronounced inhibition of ATP hydrolysis by the chloroplast ATP synthase and F1 ATPase (CF1) is bound at catalytic sites or at noncatalytic regulatory sites or both has been uncertain. We have used photolabeling by 2-azido-ATP and 2-azido-ADP to ascertain the location, with Mg2+ activation, of tightly bound ADP (a) that inhibits the hydrolysis of ATP by chloroplast ATP synthase, (b) that can result in an inhibited form of CF1 that slowly regains activity during ATP hydrolysis, and (c) that arises when low concentrations of ADP markedly inhibit the hydrolysis of GTP by CF1. The data show that in all instances the inhibition is associated with ADP binding without inorganic phosphate (Pi) at catalytic sites. After photophosphorylation of ADP or 2-azido-ADP with [32P]Pi, similar amounts of the corresponding triphosphates are present on washed thylakoid membranes. Trials with appropriately labeled substrates show that a small portion of the tightly bound 2-azido-ATP gives rise to covalent labeling with an ATP moiety at noncatalytic sites but that most of the bound 2-azido-ATP gives rise to covalent labeling by an ADP moiety at a catalytic site. We also report the occurrence of a 1-2-min delay in the onset of the Mg2+-induced inhibition after addition of CF1 to solutions containing Mg2+ and ATP, and that this delay is not associated with the filling of noncatalytic sites. A rapid burst of Pi formation is followed by a much lower, constant steady-state rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901856 TI - Rat pulmonary surfactant protein A is expressed as two differently sized mRNA species which arise from differential polyadenylation of one transcript. AB - In rat, the surfactant-associated glycoprotein A, SP-A, is encoded by two mRNA species of 0.9 and 1.6 kb. Each transcript is polyadenylated and is found in approximately the same ratio in total cellular RNA isolated from either alveolar type II cells or from whole lung. The two mRNA species have identical coding regions and differ only in the length of the 3' untranslated sequences. Restriction analysis and partial sequence analysis of rat genomic clones indicate that each mRNA species arises from one gene, with the difference in size most easily accounted for by differential polyadenylation. During fetal development, the accumulation of mRNA encoding SP-A is detectable by day 18 but increases many fold on day 19. However, there are no apparent alterations in the prevalence of either mRNA species during fetal development or in the early postnatal period. PMID- 2901857 TI - Dietary cholesterol and/or n-3 fatty acid modulate delta 9-desaturase activity in rat liver microsomes. AB - delta 9-Desaturase activity and fatty acid composition of liver microsomal phospholipids in rats fed diets enriched with either saturated (hydrogenated beef tallow) or alpha-linolenic (linseed oil) or eicosapentaenoic and docosahexaenoic (fish oil) acids with or without 2% cholesterol supplementation were investigated. Both the linseed oil and the fish oil diets inhibited delta 9 desaturase activity in the rat liver microsomes. The inhibition was greater when feeding fish oil (90%) compared with the linseed oil (60%) diet. Dietary cholesterol feeding accelerated conversion of palmitic (16:0) to palmitoleic (16:1) acid, irrespective of the fatty acid supplement. Feeding the linseed oil diet decreased, while feeding the fish oil diet increased synthesis of the monounsaturated fatty acids of n-7 series (palmitoleic and vaccenic acid) and decreased 18:1(n-9) in microsomal membrane lipids when compared with animals fed beef tallow. Addition of 2% cholesterol to the otherwise low cholesterol diets led to accumulation of 16:1(n-7), and 18:1(n-9) in microsomal membranes. These results suggest that delta 9-desaturase activity is dependent on the cholesterol contents as well as the n-3 fatty acid content of microsomal membranes on which it is localized. PMID- 2901858 TI - The occurrence of aminopeptidase N and desquamated cell proteins in intestinal perfusate of the rat. AB - The in vivo release of a microvillar enzyme, aminopeptidase N (EC 3.4.11.2), and a cytosolic enzyme, lactate dehydrogenase (EC 1.1.1.27), into the intestinal lumen was measured to gain information on the fraction of desquamated cell protein in intestinal juice and on the mechanism of release of intestinal microvillar enzymes. 1.6% and 2.9% of the mucosal activities of aminopeptidase N and lactate dehydrogenase were released to the intestinal lumen per hour, respectively. The ratios between aminopeptidase N and lactate dehydrogenase in intestinal perfusates and mucosal homogenates were similar. This result is compatible with the view that aminopeptidase N in the rat small intestine is predominantly released into the intestinal lumen by desquamation of enterocytes. This conclusion was supported by the failure to demonstrate microvesiculation of the microvilli by electron microscopy. 30-40% of the aminopeptidase N in the intestinal lumen is membrane-bound indicating that partial solubilization occurs during desquamation. The addition of calcium ions did not augment the release of aminopeptidase N or the membrane-bound fraction in the lumen. 10-20% of the protein content in the intestinal lumen is due to extruded cell protein. This includes aminopeptidase N which constitutes 1% of the luminal protein. PMID- 2901859 TI - Pathways for organic osmolyte synthesis in rabbit renal papillary tissue, a metabolic study using 13C-labeled substrates. AB - Renal papillary collecting duct cells have been postulated to adapt their intracellular osmolality to the large changes in interstitial osmolality by changing their content of 'non-perturbing' organic osmolytes such as sorbitol and myo-inositol. 13C-NMR was used in this study to elucidate the metabolic pathways leading to a synthesis of those compounds. Incubation of rabbit renal papillary tissue with [1-13C]glucose showed label scrambling mainly into sorbitol (C-1) and lactate (C-3). This result confirms activity of aldose reductase and glycolytic enzymes in renal papillary cells. Using [3-13C]alanine or [2-13C]pyruvate as carbon source, 13C-labeling of sorbitol and myo-inositol was observed, indicating that renal papillary tissue possesses, in addition, gluconeogenic activity. The latter assumption is supported by the result that in enzyme assays rabbit kidney papilla and isolated rat kidney papillary collecting duct cells show significant fructose-1,6-bisphosphatase activity. PMID- 2901860 TI - Phospholipase C in rabbit thymocytes: subcellular distribution and influences of calcium and GTP gamma S on the substrate dependence of cytosolic and plasma membrane-associated phospholipase C. AB - The subcellular distribution of phospholipase C (PLC) activity in rabbit thymocytes was examined by measuring the enzyme's activity in different subcellular fractions. PLC activity was determined using exogenously added [3H]PIP2 as substrate. Approx. 80% of the activity of the cell homogenate was found in the cytosolic fraction. A minor portion of PLC activity was attached to the particulate fraction. This membrane-associated PLC activity was found to be predominantly bound to the plasma membrane. Both PIP2-cleaving PLCs (the PLC associated with the plasma membrane and the PLC in the cytosol) exhibited maximum activity at pH 5. GTP gamma S stimulated the cytosolic and the membrane-bound PLC. As revealed by computer analysis of the substrate dependence of both basal and GTP gamma S-stimulated PLC activity, GTP gamma S enhanced the Vmax of the enzymes. Calcium, at a concentration of 1 mM, decreased PLC activity, as compared to a calcium concentration of 100 nM. The characteristic increase in Vmax induced by GTP gamma S was observed at a concentration of 1 mM calcium and was similar to that at 100 nM. These data suggest that the stimulatory effect of GTP gamma S is not due to an increased affinity of PLCs to calcium. PMID- 2901862 TI - Structural and immunochemical properties of rat liver tyrosine aminotransferase. AB - Our results show for the first time sequence data of the N-terminal part of tyrosine aminotransferase. This unblocked form of TATase, which has never been detected before, starts with a serine. This serine was found at position 29 of the primary structure of the enzyme deduced from the cDNA. We suggest that this free N-terminal amino acid is the extremity of a TATase form generated by proteolysis during the process of purification. Thus, proteolysis does not occur at the C-terminal as has been suggested before, but rather at the N-terminal region of the enzyme. To confirm this possibility, a peptide corresponding to the sequence of the seven carboxy-terminal amino acids of TATase was synthesized. It was coupled to ovalbumin or keyhole limpet hemocyanin, and the resulting conjugates were used to raise anti-peptide antibodies. The crude sera obtained were purified and their abilities to recognize TATase in ELISA and dot-blot experiments were proven. Our results demonstrate that the C-terminal part of the enzyme is present and well-recognized by the anti-peptide serum prepared. Furthermore, the anti-peptide serum reacts with TATase without inhibiting its enzymatic activity. PMID- 2901861 TI - Phosphorylation of phosvitin by casein kinase-2 provides the evidence that phosphoserines can replace carboxylic amino acids as specificity determinants. AB - The consensus sequence of casein kinase-2 consists of a serine (threonine) followed by a cluster of glutamic and/or aspartic acids, the one at position +3 playing an especially crucial role (Marin et al., (1986) Eur. J. Biochem. 160, 239-244 and Kuenzel et al. (1987) J. Biol. Chem. 262, 9136-9140). None of the 123 serines of the main phosvitin component (34 kDa) fulfils such a requirement (Byrne et al. (1984) Biochemistry 23, 4275-4279), rather, most of them are clustered into stretches of up to 14 entirely phosphorylated residues. Three out of the four threonines lie close to the N-terminal side of such phosphoseryl blocks. Here we show that native 34 kDa phosvitin is a poor substrate of casein kinase-2, its radiolabeling occurring mostly at threonine residue(s); a very slight (1%) previous dephosphorylation with acid phosphatase converts phosvitin into an excellent substrate for casein kinase-2, its phosphorylation occurring almost exclusively at serine residues. Extensive dephosphorylation however (greater than 40%) reduces the phosphorylation efficiency of casein kinase-2. These results show that phosphoserine residues can replace carboxylic residues as specificity determinants for casein kinase-2. PMID- 2901863 TI - Synthesis and characterization of CGP-12177-NBD: a fluorescent beta-adrenergic receptor probe. AB - The synthesis and properties of a fluorescent derivative of the hydrophilic beta adrenergic antagonist CGP-12177 are described. The fluorescence of the NBD derivative of CGP-12177 (CGP-NBD) is extremely sensitive to its environment, the quantum yield increasing 23-fold upon transfer from water to acetonitrile. This property of CGP-NBD was taken into account and a procedure was developed using quantitative chloroform extraction of ligand for the measurement of CGP-NBD bound specifically to beta-receptors on A431.E3 membranes. The fluorescent NBD derivative of CGP-12177 bound strongly and specifically to A431 cells, a KD of 3.9 x 10(-10) M being measured; the specific binding represented 63% of the total binding at a concentration of 1 x 10(-8) M (256 x KD). A431.E3 cells were used for the binding studies since they gave consistently higher receptor numbers when compared with the native strain. A maximal number of 47,000 sites/cell and a KD of 100 pM were measured with CGP-12177 on adhered cells. The receptor number was strongly dependent upon cell density with only 3000 sites/cell being measured in suspension at confluence. PMID- 2901864 TI - [The sites of high affinity binding of L-[3H]glutamic acid in human platelets. A new type of platelet receptor?]. AB - The total membrane fraction of human platelets was found to contain high affinity sites of L-[3H]glutamic acid binding (Kd = 100 nM, Bmax = 1.06 pmol/mg protein). The pH optimum for binding is at pH approximately 6.9 Na+ (1-150 mM) inhibit glutamate binding by platelet membranes (IC50 = 12 mM). Ca2+ (50-100 microM) stimulate the binding by 10-20% and inhibit it by 20-30% at concentrations of 1-5 mM. Monoclonal antibodies to the glutamate receptor strongly suppress the L [3H]glutamate binding by platelet membranes (IC50 = 300 nm). The presence in human platelets of a glutamate-sensitive receptor complex similar to the central nervous system glutamate receptor is postulated. PMID- 2901865 TI - CSF somatostatin in Alzheimer's disease, depressed patients, and control subjects. PMID- 2901866 TI - Permanent loss in stem cell self renewal capacity following stress to the marrow. AB - A technique of irradiating the entire mouse except for one hind limb was developed to provide repeated proliferative demand on the stem cell pool. Animals received 200 cGY weekly for a total dose of 3,400 to 4,000 cGy. During irradiation, shielded bone marrow cellularity was similar to that of unirradiated controls. Shielded marrow colony-forming unit (CFUs) content increased while marrow CFUs self renewal capacity decreased as compared with unirradiated age matched controls. Following irradiation experimental animals were monitored monthly for 10 to 12 months for marrow cellularity, CFUs content, and self renewal capacity. Shielded marrow cellularity and CFUs content remained elevated over age-matched controls throughout the period of observation. These findings are compatible with the requirement of the shielded hind limb to provide hematopoietic support for the remainder of the animal. Shielded marrow self renewal capacity, a measurement reflecting primitive hematopoietic stem cell function, remained depressed and did not recover with time. These experiments provide evidence for there being limitations on the self renewal capacity of the stem cell compartment. While the small amount of shielded marrow had sufficient capacity to support the animal its average self renewal capacity was permanently reduced. PMID- 2901867 TI - A novel beta-thalassemia frameshift mutation (codon 14/15), detectable by direct visualization of abnormal restriction fragment in amplified genomic DNA. AB - A new frameshift mutation due to an insertion of G between codon 14/15 of the beta-globin gene was found in two unrelated Chinese patients with Cooley's anemia. The first patient (W.S.) was homozygous for haplotype 5 (Chinese) and carried a codon 41/42 (four base pair deletion) mutant, while the second patient (C.K.) was homozygous for haplotype 2 (Chinese), and also had a codon 17 (A----T) nonsense mutation. Molecular cloning and M13 sequencing of the beta gene in patient W.S. revealed that the new mutant was found in a beta-globin gene framework type 3 (Asian). Direct sequencing was performed on polymerase chain reaction-amplified genomic DNA from patient C.K. With the new mutation, an additional BstNI or EcoRII recognition site is generated and the abnormal restriction fragment (134 basepair) can be directly visualized on polyacrylamide gel electrophoresis of the amplified genomic DNA. PMID- 2901868 TI - Histamine H2-receptor antagonists. AB - The first histamine H2-receptor antagonists were developed in the early 1970s, and they have a dominant role in today's management of peptic ulceration. The original regimens using either cimetidine or ranitidine attempted to control acidity across the 24 hours, but more 'modern' regimens use a large single dose of the H2-blocker in the evening, which produces a pulse of decreased intragastric acidity during the night with a normal acidity in the daytime. High dose regimens using a new generation of extremely potent histamine H2-receptor antagonists may improve ulcer healing rates at 4 weeks, and may be particularly useful for the management of either severe oesophagitis or intractable duodenal ulceration. PMID- 2901869 TI - Rates of tranquillizer prescribing in primary care. PMID- 2901870 TI - Circulating stem cell autografts. AB - The role of autologous bone marrow transplantation in the treatment of malignant disease is currently being evaluated. The peripheral blood represents an alternative source of haemopoietic progenitors and the use of circulating rather than bone marrow stem cells permits autografting in patients with infiltrated bone marrows. It may also offer a lower risk of tumour contamination, although this is not yet proven. Several autografts using circulating stem cells (CSCs) have recently been reported. These are reviewed and current uncertainties and future prospects are discussed. PMID- 2901871 TI - Clonogenic assays and engraftment in allogeneic bone marrow transplantation. AB - The significance of clonogenic assays for determining the hematopoietic potential of bone marrow grafts is still a matter of controversy. We determined the number of myeloid (GM-CFU), early erythroid (BFUe) and mixed (CFU-GEM) clones in 23 consecutive allogeneic bone marrow grafts. The growth of GM-CFU was stimulated by placental-conditioned medium, whereas both phytohemagglutinin-stimulated leucocyte-conditioned medium (PHA-LCM) and 'pluripoietin' from the 5637 cell line served as equally efficient stimulators of BFUe and CFU-GEM growth. Plating efficiency (e.o.p.) of GM-CFU and numbers of myeloid and mixed progenitors transplanted per kg body weight were significantly lower in those patients who died in the aplastic phase 2-6 weeks postgrafting (n = 4). These data show that low numbers of clonogenic cells, in particular GM-CFU, indicate a higher risk of death from infection following bone marrow transplantation (BMT) and argue for a contribution of GM-CFU in the seeding of an aplastic bone marrow. PMID- 2901872 TI - Clinical application of Percoll gradient-separated bone marrow. AB - We have evaluated the transplantation potential of bone marrow stem cell concentrates isolated from the 40/60% interface of discontinuous Percoll gradients. This mononuclear fraction is free from platelets and depleted of granulocytes, and contains the majority of granulocyte-macrophage colony-forming cells (GM-CFC), erythroid burst-forming units (BFU-E), and granulocyte, erythroid, macrophage, megakaryocyte colony-forming cells (GEMM-CFC) in less than 10% of the cell number of the original buffy coat. This preparation allows further manipulation without the clumping and cell loss associated with buffy coat cell preparations. Cells isolated by this technique were evaluated for hematopoietic restoration potential in 14 patients who received allogeneic bone marrow transplants as supportive therapy after high dose cytoreduction to treat leukemias or lymphoma. The number of nucleated cells infused varied from 1.6-5.5 X 10(7)/kg, and the number of GM-CFC infused ranged from 0.4 to 3.7 X 10(5)/kg. There was an inverse relationship between the time to recovery of granulocytes and platelets and the number of GM-CFC infused when fewer than 10(5) GM-CFC/kg were transplanted. Above this dose, there was recovery within 10-15 days after transplantation. The stem cell-enriched fraction contained 30-40% of the original number of T lymphocytes, and acute graft-versus-host disease was observed in seven of these patients. PMID- 2901873 TI - DNA-RFLP typing in the selection of related bone marrow donors. PMID- 2901874 TI - Peripheral blood stem cells collected in very early remission produce rapid and sustained autologous haemopoietic reconstitution in acute non-lymphoblastic leukaemia. AB - Haemopoietic reconstitution was achieved in a patient with acute non lymphoblastic leukaemia (ANLL) in relapse who was autografted with blood-derived stem cells collected during very early remission. The patient received a myeloid progenitor cell dose of 230 x 10(4) CFU-GM/kg body weight. Engraftment was evident in the bone marrow 7 days post-graft. Normal neutrophil and platelet counts were attained by day 14 and blood counts remained normal thereafter. An overshoot in peripheral blood haemopoietic progenitor levels occurred at the end of the second week, presumably the progeny of a family of early progenitor cells. The completeness of haemopoietic reconstitution is further illustrated by the satisfactory nucleated cell and myeloid progenitor cell yield when a bone marrow harvest was performed 4 1/2 months post-graft. Seven months post-graft, the patient remained in complete remission with normal blood counts and bone marrow cellularity, although haemopoietic progenitor levels were slightly reduced. The rapid recovery minimises aplasia-related risks and suggests that such autografting can be carried out safely in first remission. We propose that autografting using very early remission blood cells is a new therapeutic option for patients with acute ANLL. PMID- 2901875 TI - Immune reconstitution following peripheral blood stem cell autografting. PMID- 2901876 TI - CD4+ T cells appear capable of initiating graft-versus-host disease across non major histocompatibility complex (MHC) barriers in man. AB - Twelve patients with haematological malignancy received cyclophosphamide 120 mg/kg, fractionated total body irradiation 12 Gy, oral cyclosporin and an HLA identical sibling marrow transplant depleted of T cells by incubation with monoclonal antibodies directed against the CD2 and CD8 antigens and rabbit complement. The phenotype of the residual T cells in the donor marrow inocula was CD3+, CD4+, CD8-. To exclude the possibility that this represented modulation or blocking of the CD8 antigen, T-depleted and non-depleted marrow aliquots from these donors were bulk-cultured for 10 days with phytohaemagglutinin and interleukin-2. Even after this attempted expansion, only a small proportion of cultured T cells from the depleted aliquots (in contrast to the non-depleted aliquots) expressed the CD8 antigen. Since all patients receiving CD3+, CD4+, CD8 marrow developed mild or moderate acute graft-versus-host disease (GVHD), we conclude that CD4+ T cells are capable of initiating acute GVHD across non-MHC barriers in man. PMID- 2901877 TI - Suppressor T cells in allogeneic bone marrow chimeras. AB - Immunosuppression is believed to play a role in the maintenance of stable bone marrow (BM) chimeras. This study investigates the nature and specificity of the suppression that lymphocytes from allogeneic BM chimeras exert upon the alloreactivity of donor and recipient lymphocytes. Lethally irradiated CBA/J (H 2k) mice were infused with 10(7) unseparated (WBM) or T cell-depleted BM (TDBM) cells of B10.BR mice (H-2k, disparate at minor histocompatibility antigens). Mixtures consisting of spleen cells (SC) from BM chimeras and SC from either normal donor, recipient, or third party (C3H, H-2k) mice, were sensitized with irradiated BALB/c (H-2d) leukocytes, then assayed for proliferative and anti-H-2d cytotoxic activity and compared with those of appropriate control cultures. The alloreactivity of all three types of normal SC was non-specifically suppressed by SC from both WBM and TDBM chimeras taken 2 weeks post-BM transplantation (BMT). In contrast, at 4 weeks post-BMT, SC from both chimeras suppressed the alloreactivity of recipient-type cells whereas only SC from WBM, but not from TDBM chimeras, suppressed normal donor-type response, and neither could suppress the response of normal third party cells. The suppression of donor-type alloreactivity diminished with time, while that exerted on recipient-type lasted for at least 10 weeks post-BMT. The suppression of donor alloreactivity was mediated by radioresistant Thy1.2+, Lyt1+2+ cells while that exerted upon recipient's alloreactivity was mediated by radiosensitive Thy1.2+, Lyt1+2- cells. Both types of suppressor cells were of donor origin. The potential biological role of the suppressive activity in the engraftment of allogeneic BM is discussed. PMID- 2901878 TI - T lymphocyte depletion of human peripheral blood and bone marrow using monoclonal antibodies and magnetic microspheres. AB - It has previously been demonstrated that graft-versus-host disease can be overcome in patients receiving HLA-mismatched bone marrow transplants by prior in vitro depletion of T lymphocytes from the marrow. In this report we describe the use of monoclonal antibodies and magnetic microspheres for the depletion of T cells from peripheral blood and bone marrow. The target cells are sensitized with antibodies directed against the CD2, CD3, CD4 and/or CD8 cell surface antigens, captured by magnetic beads coated with sheep anti-mouse IgG antibody and collected by placing the cell suspension in a magnetic field. This simple, rapid procedure results in the efficient removal of T cells from peripheral blood and from bone marrow without affecting the colony-forming potential of normal hematopoietic stem cells. The procedure is capable of being scaled up for the treatment of larger volumes of marrow that are required for clinical transplantation. PMID- 2901879 TI - Generation of CD8 cytolytic T cells early after autologous or allogeneic bone marrow transplantation. AB - Longitudinal in vitro assays related to cell-mediated immunity were performed in patients following allogeneic (32) or autologous (15) bone marrow transplantation (BMT). In both groups of reconstituted patients, low CD4+/CD8+ T cell ratio and weak allogeneic mixed lymphocyte reactions were found in the first 6 months after BMT, progressively reaching values similar to controls (bone marrow donors or unrelated individuals). In contrast, a strong generation of allogeneic cytotoxic cells, assessed by the number of lytic units per 10(6) cells, was frequently found (18/38 patients tested in both groups) in the first 4 months, despite the quantitative deficit of the CD4+ subset. This in vitro differentiation was found to be independent of in vivo acute graft-versus-host disease (GVHD) and chronic GVHD in allo-transplanted patients. As also documented in autologous recipients, this observation suggests that this phenomenon could be, at least partially, related to the transplantation per se. Preliminary characterization of the effector cells indicates that they belong to the CD8+ subset and that their differentiation is interleukin-2-dependent. Experimental depletion of the CD4+ subset in normal subjects did not increase the number of lytic units in allogeneic cultures. This implies qualitative differences between BMT recipients and normal subjects, namely in CD8+ subset: i.e. that following BMT early CD8+ T cells appear to produce their own growth factor (IL-2), while in normal adult individuals, such autocrine CD8+ T cells, if present, are very rare. PMID- 2901880 TI - Concentration of bone marrow progenitor cells by separation on a Percoll gradient using the Haemonetics model 30. AB - To perform an optimal ex vivo bone marrow purge, it is necessary to concentrate the bone marrow progenitor cells and to eliminate both the red blood cells and the polymorphonuclear leucocytes. To achieve this goal which cannot be accomplished by using the Haemonetics model 30 alone, we used the Haemonetics model 30 and a density gradient together in a two-step procedure. In the first step we obtained the buffy coat from original bone marrow grafts and in the second we reintroduced these buffy coats into the Haemonetics bowl followed by Percoll, adjusted to 1.079 g/ml, at 5 ml/min in order to recover the light density mononuclear cells. After this second step, the mean volume of the marrow and the RBC and nucleated cell contaminations were reduced to 9%, 0.96% and 16% of their original values the unseparated bone marrow, respectively. This was far better than the values obtained after the first step (volume: 19%; RBC: 10%; nucleated cells: 54%). The CFU-GM recoveries after the first and second steps were 71% and 70% of the original samples, respectively. The entire procedure lasted between 75 and 150 min. At this time, 17 of the 24 patients whose bone marrow was separated using Percoll gradient in the Haemonetics bowl have been grafted. Thirteen of these 17 patients had an evaluable haematological recovery which was complete and rapid for all but one patient with acute myeloid leukaemia. These results demonstrate that the introduction of a density gradient into the Haemonetics model 30 bowl is possible and effective. The reduction in total volume and cell number permits ex vivo purging, without decreasing the grafting capability. PMID- 2901881 TI - Hemopoietic and immune reconstitution following peripheral blood stem cell autografting in acute leukemia. PMID- 2901882 TI - Fast hematological reconstitution after combined infusion of autologous bone marrow purged with mafosfamide and autologous peripheral blood stem cells in a patient with Ewing sarcoma. PMID- 2901883 TI - The origin of stromal cells in patients treated by bone marrow transplantation. AB - The source of stromal cells following bone marrow transplantation has been investigated by culturing marrow cells obtained from patients who have a graft cells from a donor of the opposite sex. Two culture systems have been used for these studies. The first supports the proliferation of fibroblast colony-forming cells (F-CFC) and the formation of confluent layers of fibroblastoid cells; the second (the long-term bone marrow culture system) results in the formation of a complex and heterogeneous layer of adherent cells composed of fibroblasts, fat cells, endothelial cells, macrophages and 'blanket' cells. A survey of the work done using these culture systems shows that, although the issue of the transplantability of stromal cells remains controversial, it now seems reasonably certain that repopulation of the fibroblast component by donor cells is rare. In contrast, one study has shown that endothelial-like cells can engraft in transplant recipients. Another study has demonstrated a donor origin for the macrophages found in long-term cultures of marrow from transplanted patients. This finding might have been predicted because macrophages are derived from haemopoietic stem cells. PMID- 2901884 TI - Assessment and management of pathological gambling. AB - This article describes a brief treatment--imaginal desensitization--which enables pathological gamblers to retain control of gambling, discusses its development and advances evidence from 2-9 years' follow-up of its efficacy. PMID- 2901885 TI - Depressive syndromes in the year following onset of a first schizophrenic illness*. AB - A complete, unselected series of 68 patients who were seen during their first episode of an undoubtedly schizophrenic illness, and followed up one year later (for 56 patients) is described clinically. Depressive symptoms were common at onset, and 22% of patients could have been considered cases of depression from these symptoms alone. At follow-up, depressive symptoms had reduced in prevalence and only 7% of subjects were depressed cases. Only two cases of depression at follow-up had not been cases at onset. These changes could not be attributed to the use of antidepressants or ECT. Depressive syndromes could be distinguished from akinesia and the negative syndromes. The findings indicate that depression cannot be attributed solely to the administration of neuroleptics. PMID- 2901886 TI - In vivo assay for neuroleptic receptor binding in the striatum. Positron tomography in humans. AB - Using PET, we investigated the potency in six patients of therapeutic doses of neuroleptic drugs for preventing specific binding of trace doses of intravenously administered 76Br-labelled bromospiperone to corpus striatum in vivo. Measured receptor occupancy showed a clear-cut dose-dependent saturation curve with increasing daily oral dose of neuroleptics, indicating the validity and reliability of the method when used as an in vivo radioreceptor assay. Following drug withdrawal in eight patients, recovery to normal or supranormal receptor availability occurred in a matter of days. The results demonstrate an approach that may help resolve controversies about, and design better strategies for, neuroleptic treatment schedules. PMID- 2901887 TI - Substance-use disorders in DSM-III-R. Evidence for the dependence syndrome across different psychoactive substances. AB - Using the newly revised DSM-III-R criteria for substance-abuse diagnoses, we examined dependence syndrome elements among 83 psychiatric patients. The sample included 14 with no history of substance abuse. The remainder abused alcohol (52), sedatives (31), hallucinogens (12), stimulants (33), cannabis (44), cocaine (52), or opiates (47). Many patients (52) had abused more than one type of drug. Ten items assessing the proposed dependence symptoms for each type of drug were factor-analysed. The dependence syndrome items formed a single factor for opiates, cocaine, and alcohol, but not for other drugs. When the items were combined into cumulative scales, they had excellent internal consistency. Furthermore, they formed good approximations of unidimensional Guttman scales on which higher scores indicated greater syndrome severity. The items associated with higher scores differed across drugs, with opiates having the most striking differences from the other substances. Medical-psychosocial consequences were relatively independent of the dependence syndrome, although alcohol and cocaine dependence had some association with other problem areas. These findings support the utility of a common dependence syndrome concept for drugs of abuse as well as alcohol, and provide empirical support for the current revision of the DSM-III diagnostic criteria. PMID- 2901888 TI - Khat-induced paranoid psychosis. PMID- 2901889 TI - Calcium therapy for neuroleptic-induced extrapyramidal symptoms. PMID- 2901890 TI - Molecular genetics and human disease. Implications for modern psychiatric research and practice. AB - Techniques of molecular genetics, including recombinant-DNA technology, are likely to have a key role in modern psychiatric research and practice. This article reviews some methods of DNA analysis and their applications to clinical science: specifically, how these methods can be used to localise, identify, isolate, and clone clinically important genes, and how this should enable us to elucidate the molecular pathology of most inherited (psychiatric) disorders. The implications of these developments for prevention and treatment of genetic disease are discussed. PMID- 2901891 TI - Influence of climate on the prevalence of mania. AB - Monthly rates of admission of manic patients to the Department of Psychiatry in Galway Regional Hospital were examined for a five-year period. Monthly variation in admission rates was compared with monthly levels of sunshine, temperature and daylength. Results indicated a significant seasonal variation in the prevalence of mania: admission rates were higher in the sunnier months and in months with a greater average daylength. It is suggested that the presentation of mania in this fashion is due to an abnormal response to light in these patients. PMID- 2901892 TI - Catatonia in a 90-year-old patient after depot pipothiazine injection. PMID- 2901893 TI - Bilateral spontaneous descent of the testis after the age of 10: subsequent effects on fertility. AB - Fertility after late spontaneous descent of the testes in 45 men with previous bilateral undescended testes was evaluated on the basis of seminal analysis and concentrations of follicle-stimulating hormone (FSH) in serum. Only 15 (33 per cent) were found to have a normal fertility as estimated from the results of the total semen analysis, whereas 21 (47 per cent) were classified as being sterile or having severely reduced fertility. Elevated serum FSH concentrations in the majority of men with subnormal sperm densities supported the results of the semen analysis, indicating impaired spermatogenesis. These findings suggest that the expectant attitude in the treatment of cryptorchidism does not seem to be justified in terms of fertility and combined with recent histomorphological studies favour a more active and early treatment of undescended testes. PMID- 2901894 TI - Epileptiform events induced by GABA-antagonists in entorhinal cortical cells in vitro are partly mediated by N-methyl-D-aspartate receptors. AB - The effects of the GABA-antagonists, picrotoxin and bicuculline on responses of medial entorhinal cortical cells to subicular stimulation were tested in vitro. On every cell tested either antagonist caused a profound enhancement of synaptically evoked depolarizations to the point where paroxysmal depolarizing shifts (PDS) were recorded, although only a minority of cells showed evidence of inhibitory potentials in the control situation. The initial PDS was followed by either a long afterdepolarization or a series of afterdischarges. The afterpotentials were always reduced or blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonovalerate (2-AP5). The amplitude of the initial PDS in many cells was also reduced by 2-AP5. Thus, entorhinal cortical cells are susceptible to epileptogenesis induced by a reduction of GABAergic inhibition and the paroxysmal events contain a large, NMDA-receptor mediated component. PMID- 2901895 TI - Enhancement of morphine-induced analgesia after repeated injections of methylenedioxymethamphetamine. AB - Repeated administration of methylenedioxymethamphetamine (MDMA) to rats results in long-term depletion of serotonin (5-hydroxytryptamine; 5-HT) in several brain regions. Because of the apparent role of 5-HT in morphine-induced antinociception, the present experiment was designed to determine the effects of repeated MDMA injections on morphine-induced analgesia. Rats (n = 48) received 8 s.c. injections (one every 12 h for 4 days) of MDMA (20 mg/kg) or saline (1.0 ml/kg). Two weeks after the last injection, the groups were divided into 4 subgroups that received either saline, or morphine 2.5, 3.55 or 5.0 mg/kg (s.c.). Nociception was assayed before and after saline or morphine administration by the method of tail immersion in warm water (55 degrees C). The day after analgesia testing, the animals were sacrificed, brains and spinal cords removed and 5-HT, norepinephrine (NE) and dopamine (DA) levels in various brain and spinal cord regions were assayed. The analgesic effect of morphine was enhanced in rats that had received repeated MDMA injections. MDMA selectively depleted 5-HT in the cortex, hippocampus, striatum, brainstem and in the cervical portion of spinal cord. However, 5-HT levels were not changed in the thoracic and lumbar segments of the spinal cord. Thus, a functional consequence of repeated MDMA administration in rats was to enhance morphine-induced antinociception in association with reductions in brain and cervical spinal cord 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901896 TI - Dopaminergic nigrotectal projection in the rat. AB - After injecting a fluorescent tracer (Fluoro-gold) into the rat superior colliculus, retrogradely labeled neurons in the rostral, ventrolateral portions of the substantia nigra pars reticulata were also immunohistochemically labeled with tyrosine hydroxylase antisera. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) pretreatment of the medial forebrain bundle resulted in the disappearance of the nigral neurons double-labeled with the two markers. The existence of a dopaminergic nigrotectal projection susceptible to MPTP might provide a morphological substrate for abnormal saccadic eye movements in parkinsonism. PMID- 2901897 TI - Effects of bath-applied L-glutamate and related chemicals on the afferent synapse of the Plotosus electroreceptor. AB - Tonic electroreceptors of the marine catfish Plotosus were isolated, and effects of chemicals applied in the bath were examined in terms of firing rate (F) responses in single unit afferent nerve. L-Glutamate (L-Glu) and agonists caused marked F increase in the spontaneous discharge. Their potencies, estimated from concentrations for 50% of max F increase, were in the order of quisqualate (2 microM), kainate (7 microM), L-Glu (0.4 mM), L-homocysteate (0.4 mM), D-Glu (3 mM) and L-aspartate (L-Asp, greater than 10 mM). N-Methyl-D,L-aspartate (10 mM) had no effect. L-Glu induced F increase also in the receptors fully suppressed either by cathodal pulses or by high Mg (15 mM), which indicated the postsynaptic action. The synaptic responses were often affected differently in the fast and slow phases, here termed as the peak F and the adapted F, respectively. L-Asp potentiated only the adapted F. Kynurenic acid (Kyn) suppressed only the adapted F, but incompletely and rather dose-independently. Kyn, however, competitively antagonized the amino acid-induced responses. The present results suggest the presence of two distinct postsynaptic receptors, one a Kyn-sensitive Glu receptor that is responsible for part of the adapted F, and the other still undetermined that is responsible for most of the synaptic responses. PMID- 2901899 TI - Two compartment pharmacodynamics of somatostatin in non-obese non-insulin dependent diabetes. PMID- 2901898 TI - Neurochemical characteristics of a postsynaptic density fraction isolated from adult canine hippocampus. AB - Postsynaptic density and synaptic membrane fractions isolated from hippocampal tissue have been compared to those previously isolated from cerebellum and cerebral cortex. In all respects examined, the isolated hippocampal preparations are similar to the cerebral cortex fractions. The morphology of the postsynaptic density (PSD) preparation is the same and the protein composition is similar, but with higher concentrations of the 51-kDa major protein and of calmodulin, and lower concentrations of actin, in the hippocampal PSD fraction. The binding characteristics for glutamate and GABA are also similar between the two fractions, but with higher Bmax and KD glutamate values and lower Bmax and higher KD GABA values for the hippocampal PSD preparation. Both preparations contain GABAA and GABAB receptors. The PSD fraction contains, as does the cerebral cortex fraction, a calmodulin-dependent binding of the Ca2+ channel antagonist, nitrendipine, as well as a cAMP-dependent and a Ca2+/calmodulin-dependent protein kinase, with the same respective substrates. The value of the hippocampal fractions for studies on long-term potentiation and on kindling in the hippocampus is discussed. PMID- 2901900 TI - Neural control of canine colon motor function: studies in vivo. AB - The responses of the circular muscle of canine colon to stimulation of intrinsic nerves and to the probable mediators of these nerves were studied in vivo. In vivo studies were carried out using close intra-arterial injections and local field stimulation of proximal, mid-, and distal colon while recording circumferential contractions. Our results suggest that acetylcholine is the major excitatory mediator, but another excitatory mediator could be released by high frequency field stimulation after atropine. Norepinephrine had mixed inhibitory and excitatory effects, but no evidence was obtained that it was released by field stimulation. Substance P had mainly excitatory effects partly by a mechanism involving nerves and partly by a direct effect on muscle; it in addition to norepinephrine deserves further evaluation as the mediator of noncholinergic excitation to high frequency field stimulation. There is no explanation of the inhibition it produced after initial excitation during field stimulation. Vasoactive intestinal peptide had inhibitory effects but these were incomplete and inconsistent. This may be related to our inability to demonstrate relaxation or inhibition to field stimulation after atropine. Further evaluation of the possible role of vasoactive intestinal peptide and other agents as nonadrenergic, noncholinergic inhibitory mediators is required. PMID- 2901901 TI - Neural control of canine colon motor function: studies in vitro. AB - The responses of strips of the canine colon to stimulation of intrinsic nerves and to the probable mediators of these nerves were studied in vitro. Studies were carried out using longitudinal and circular muscle strips from proximal and distal colon with field stimulation and addition of agents to the bath. Overall, these and other studies in vivo suggested that acetylcholine was an ubiquitous mediator of neural excitation. Norepinephrine had mixed inhibitory and excitatory effects, the latter only in circular muscle. Inhibitory effects of norepinephrine seemed to be both pre- and post-synaptic but no evidence that it was released by field stimulation was obtained. Substance P had excitatory effects chiefly by release of acetylcholine. It, in addition to norepinephrine, at least in circular muscle, deserves evaluation as the mediator of noncholinergic excitation to high frequency field stimulation. Although vasoactive intestinal peptide sometimes had inhibitory effects, these were incomplete and inconsistent. However, further evaluation of its possible role as a nonadrenergic, noncholinergic inhibitory mediator is required to determine if it is involved as one component in the response. Few qualitative differences existed between responses of various regions of the colon to potential neuromediators, although there were some consistent differences between responses of longitudinal and circular muscle. Some differences existed in responses obtained earlier in vivo and in vitro. In particular, inhibitory effects following excitation by substance P on field stimulation were found only in vivo. Nonadrenergic, noncholinergic inhibitory responses to field stimulation were consistently present only in vitro. These differences have not been explained. PMID- 2901902 TI - In vivo modulation by alpha 2-adrenoceptors of adrenal catecholamine release in the anaesthetized dog. AB - In this study, the reversal of the potentiating effect of idazoxan, a selective alpha 2-antagonist, on adrenal catecholamine release elicited by splanchnic nerve stimulation in anaesthetized and vagotomized dogs, was investigated with the use of oxymetazoline, a selective alpha 2-agonist. Stimulation of the left splanchnic nerve (5.0-V pulses of 2 ms duration for 3 min at a frequency of 2 Hz) was applied before and 20 min after the i.v. injection of each drug. Blood samples were collected in the adrenal vein before and at the end of each stimulation. The results show that the release of catecholamines induced by electrical stimulation was potentiated by 50% after idazoxan injection (0.1 mg/kg). This enhanced response was significantly antagonized by the subsequent injection of oxymetazoline (2 micrograms/kg). The alpha 2-modulating effect appears to be related to the amount of catecholamines released during the stimulation, since by subgrouping of the data on the basis of the degree of potentiation by idazoxan, it was observed that this drug was more efficient when catecholamine release was higher during control stimulation. In contrast, the reversing effect of oxymetazoline was found to be more pronounced when catecholamine release was lower. These results thus suggest that the sensitivity of the alpha 2 adrenoceptor mechanism may depend upon the in situ concentration of adrenal catecholamine release during electrical stimulation and that the potentiating effect of alpha 2-blockade can be reversed by activation of those receptors by a selective alpha 2-agonist. PMID- 2901903 TI - Effect of dopaminergic and alpha-adrenergic modulation on corticotropin-releasing factor immunoreactivity in rat hypothalamus. AB - The potential role that dopaminergic mechanisms have in the regulation of corticotropin-releasing factor (CRF) in the hypothalamus was investigated. Adult male rats were administered bromocriptine, a potent dopamine agonist, for periods ranging up to 51 days. Overall, bromocriptine treatment resulted in a significant decline in CRF-like immunoreactivity (CRF-ir). The dopamine antagonist, haloperidol, was administered for similar periods and resulted in no overall significant effect, except for a transient decrease. Treatment with reserpine, known to deplete monoamines including dopamine, induced a significant decrease in CRF-ir 24 h post-treatment. The possibility that the original results were due to alpha-adrenergic inhibition by bromocriptine and haloperidol was studied next. alpha 1-Stimulation by administration of methoxamine had no significant effect. alpha 2-Stimulation by clonidine significantly reduced hypothalamic CRF-ir. Selective depletion of neurotransmitter from noradrenergic and adrenergic neurons by 6-hydroxydopamine also resulted in a significant reduction of hypothalamic CRF ir, an effect localized entirely to the median eminence. These results show a reduction in CRF-ir subsequent to either bromocriptine administration, generalized monoamine depletion, alpha 2-stimulation, or selective noradrenaline adrenaline depletion. No direct dopaminergic effects could be confirmed. These data are consistent with a constant, near-maximal alpha 1-adrenergic effect maintaining hypothalamic CRF concentrations, presumably by inhibition of CRF release from the median eminence. PMID- 2901904 TI - T-cell-rich lymphoproliferative disorders. Morphologic and immunologic differential diagnoses. AB - To differentiate peripheral T-cell lymphomas (PTCL), the authors evaluated the results of T11 monoclonal antibody studies on consecutive cell suspensions prepared from 509 lymph nodes from various lymphoproliferative disorders (LPD). They used T11 (CD2) positivity to identify those LPD in which the content of T cells was high. There were 266 (52%) cell suspensions which contained more than 50% T11-positive cells. More than 75% of the following non-Hodgkin's lymphomas had over 50% T11-positive cells: diffuse mixed cell (DM), diffuse atypical poorly differentiated lymphocytic and lymphoblastic lymphomas; mycosis fungoides; and true histiocytic lymphoma. Eleven cell suspensions had more than 90% T11-positive cells; four were involved by B-cell lymphomas. The cell suspensions prepared from nine of 14 diffuse large cell lymphomas of the T-cell type had more than 50% T11 positive cells. Of these, three of five cases of the polymorphous subtype had fewer than 50% T11 cells, but six of seven lymph nodes of the clear-cell type had more than 50% T11-positive cells. Each of seven DM samples of the T-cell type contained over 50% T11 cells; none had a polymorphous appearance. In the 112 cases of reactive LPD studied, more than 75% of cases of necrotizing lymphadenitis, dermatopathic lymphadenitis, angioimmunoblastic lymphadenopathy, and those with lymph nodes with no specific reactive pattern had more than 50% T11-positive cells. The authors' findings indicate that T11 positivity is a reliable T-cell marker in reactive and neoplastic LPD except for those cases of PTCL with a polymorphous appearance; these tend to lose T11-expression. A multi parameter diagnostic approach is required in the following LPD: (1) PTCL which are T11-negative; (2) PTCL of small lymphocytic type having an unremarkable T cell phenotype; (3) SIg-negative B-cell lymphomas which are rich in nonneoplastic T cells; (4) non-Hodgkin's lymphomas with minimal disease which are rich in reactive T cells; and (5) polymorphous large cell proliferations. PMID- 2901905 TI - Diagnostic significance of histiocyte-related markers in malignant histiocytosis and true histiocytic lymphoma. AB - Interrelationships of immunologic and enzymatic markers of histiocytes have been studied in malignant neoplasms of histiocytic/monocytic origin and in differential diagnostically relevant, large cell non-Hodgkin's lymphomas. Cryostat sections required for demonstrating cell surface antigens by monoclonal antibodies are inadequate for studying cellular detail, enzymatic maturation by alpha-naphthyl acetate esterase (ANAE), and demonstrating the classical cytoplasmic markers of histiocytes like lysozyme, alpha-1-antitrypsin (AT), and alpha-1-antichymotrypsin (ACT). These markers have been compared in gently fixed and vacuum paraffin-embedded material. The reactivity for monoclonal anti-human monocyte 1 (Mo 1) has also been preserved by this method. Malignant histiocytosis (MH) is characterized by a heterogeneous cell population. The mature, ANAE positive cells with macrophage morphology usually show a diffuse cytoplasmic positivity for AT and ACT. Lysozyme is moderately positive to negative in these cells, but it is more efficient than these markers in revealing smaller cells resembling monocytes by focal positivity in the cytoplasm. The expression of Factor XIIIa (F-XIIIa) is connected with the phagocytic activation of histiocytic cells. F-XIIIa positive cells usually form a minority of the neoplastic population in MH, but the large cytophagocytic marcophages are invariably positive. Reactive macrophages in large cell non-Hodgkin's lymphomas are characterized by a coexpression of ANAE, AT, ACT, lysozyme, F-XIIIa and Mo 1. Typical cases of true histiocytic lymphoma (THL) are made up of a homogeneous population showing the above mature, phagocytizing phenotype. In MH, Mo 1 and ANAE recognize different subpopulations. The reciprocal relation of these markers is an abnormal phenotypic feature. The results presented in this article prove the diagnostic value of ANAE and lysozyme in confirming the histiocytic differentiation of malignant cells. Monoclonal anti-human monocyte 1 is useful for identifying the immature component in MH. Factor XIIIa can be considered a functional marker of mature phagocytic histiocytes and an aid in the diagnosis of THL. PMID- 2901906 TI - Genes amplified and overexpressed in human multidrug-resistant cell lines. AB - Multidrug resistance (MDR) is associated with overproduction of Mr 170,000 membrane proteins (P-glycoproteins) caused by either gene amplification, transcriptional activation, or both. In rodents the amplified domain comprises genes that encode P-glycoproteins and at least five unrelated genes, one of which encodes the calcium-binding protein sorcin. The amplification and increased expression of these genes always includes one P-glycoprotein-encoding gene (pgp1 in hamsters, homologous to mdr1 in humans). In human MDR cells only elevated mdr1 expression has been shown thusfar, although another P-glycoprotein encoding gene (mdr3, homologous to hamster pgp3) is closely linked. Here we show that the human homolog of the hamster sorcin gene resides on chromosome 7 like the P glycoprotein-encoding genes. Furthermore, gene classes designated 4, 5, and 6 are coamplified with mdr1 and mdr3 in the human ovarian carcinoma cell line 2780AD, which strongly suggests that the overall structure of the human MDR domain is the same as in rodents. Class 6 was moderately and mdr1 was highly overexpressed in this cell line. Four other human MDR cell lines also have much higher mdr1 overexpression than expected from the relatively low levels (2- to 30-fold) of gene amplification. This contrasts with the results of previous work with rodent MDR cells, in which the increase in P-glycoprotein mRNA levels usually parallels the increase in gene copy number. Although four of the five human MDR cell lines have coamplified mdr3, its expression was undetectable. Our results confirm the central role of the mdr1 (pgp1) gene in MDR and suggest that different cross resistance patterns are not due to differential expression of different P glycoprotein genes. PMID- 2901907 TI - Effects of tiazofurin on protooncogene expression during HL-60 cell differentiation. AB - The synthetic nucleoside analogue, tiazofurin (2-beta-D-ribofuranosylthiazole-4 carboxamide, NSC 286193) is an inhibitor of the enzyme inosine monophosphate (IMP) dehydrogenase and depletes guanine nucleotide pools. In the present study, we have monitored the effects of tiazofurin on human HL-60 promyelocytic cell differentiation and protooncogene expression. Tiazofurin (10 microM) induced a more differentiated HL-60 cell phenotype as determined by histochemical staining and decreased myeloperoxidase gene expression. This induction of differentiation was associated with a loss of proliferative capacity and decreases in clonogenic survival. The results also demonstrate that tiazofurin induces a down-regulation of c-myc mRNA levels. In contrast, there was no detectable change in the level of 3.8-kilobase c-myb transcripts. Furthermore, treatment of HL-60 cells with tiazofurin resulted in the appearance of an additional c-myb mRNA with an apparent size of 3.3 kilobases. The addition of guanosine to tiazofurin-treated HL-60 cells prevented the down-regulation of c-myc transcripts and also inhibited induction of the 3.3-kilobase c-myb transcript. Moreover, this additional transcript was not detected during induction of HL-60 cells by dimethyl sulfoxide, tumor necrosis factor, and retinal, but was induced by another IMP dehydrogenase inhibitor, mycophenolic acid. These results suggest a role for guanosine ribonucleotides in the regulation of c-myc and c-myb gene expression during HL-60 cell differentiation. The results also suggest that changes in c-myb expression can be dissociated from that of c-myc and induction of myeloid differentiation. PMID- 2901908 TI - Biochemical characteristics of hyperplastic rat bile ductular epithelial cells cultured "on top" and "inside" different extracellular matrix substitutes. AB - An essentially pure population of bile ductular epithelial cells isolated from bile duct-ligated rats was placed in primary culture by plating the cells either "on top" of or "inside" different extracellular matrix substitutes, including basement membrane Matrigel, type I collagen gel, and agarose gel. Plating efficiencies of greater than 60% were obtained when the cells were seeded in the presence of 1.0% fetal calf serum on top of Matrigel and collagen gel, but there was very little if any cell attachment to the agarose surface. In contrast, the cells could be maintained equally well and at very similar densities when they were cultured inside the various gel substances, including agarose. Regardless of substratum condition, bile ductular cells at 10 days in primary culture expressed specific activities of the marker enzymes gamma-glutamyl transpeptidase and leucine aminopeptidase which were significantly higher than those shown by freshly isolated cells. On the other hand, alkaline phosphatase activity of the cells became undetectable by day 3 of culture when they were cultured on top of either Matrigel or collagen gel but was retained at approximately 50% of its original level in cells cultured for 10 days within Matrigel or agarose gel. Treatments with dexamethasone or hydrocortisone (i.e., 10(-6) M) inhibited the increase in gamma-glutamyl transpeptidase activity of the cultured cells but did not affect the other enzyme changes. Subcultures of the bile ductular epithelial cells were developed by passing the cells in the presence of 10% fetal calf serum on surfaces coated with either type I collagen or Matrigel. In either case, cells subjected to at least 4-6 passages (up to 100 days of culture) were still characterized by a high gamma-glutamyl transpeptidase activity. Preliminary results obtained with cells plated at very low density within Matrigel also indicated the development of cell growths that appeared to be organized in the form of distinct acinar-like structures. PMID- 2901909 TI - Medical prophylaxis for the post myocardial infarct patient. AB - The use of beta-adrenergic blocking drugs has been shown to benefit many post myocardial infarction patients. Aspirin is useful for secondary prevention and a subset of patients may benefit from short term anticoagulation. PMID- 2901910 TI - Analgesic therapy in acute myocardial infarction. AB - Parenterally administered narcotic analgesics are a critically important part of therapy for the patient with acute myocardial ischemic syndromes. These agents are very effective and, when used with appropriate caution and monitoring, are also generally safe. They not only relieve the sensation of severe pain but also reduce the effective and physiologic reaction to pain and thus reduce patient anxiety. Because these agents all depress respiratory drive to some degree in the doses used for adequate analgesia, close attention to respiratory status is mandatory. In patients with underlying pulmonary disease or significant congestive heart failure, this monitoring should be even more intensive and include arterial blood gas measurements and preparations for possible narcotic antagonist administration and ventilatory assistance. With regard to the hemodynamic changes produced by these agents, several important points are worth noting. It must be remembered that the conclusions regarding hemodynamic effects of these agents are derived from studies involving patient groups that were generally hemodynamically stable, usually pain-free, and almost always at least several hours following acute presentation. Thus, the hemodynamic effects of these agents may be quite different in patients with active pain during a period of acute ischemia, or in patients that are hemodynamically unstable. Hemodynamic studies during these acute settings, however, are extremely difficult to perform because the patient's acute distress mandates rapid administration of an analgesic agent prior to the institution of invasive monitoring. With these cautions relating to data interpretation in mind, it is still possible to make certain recommendations regarding the use of analgesic therapy in acute MI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901911 TI - Medical and surgical therapy of hypertrophic cardiomyopathy. PMID- 2901912 TI - De novo cardiac beta adrenoceptor synthesis in adult rats under normoxic and hypoxic conditions. AB - Bromoacetylalprenololmenthane (BAAM), an alkylating irreversible beta adrenoceptor antagonist, was used to study in vivo beta adrenoceptor synthesis in adult rat left ventricle under normoxic and hypoxic conditions. In normoxic conditions cardiac beta adrenoceptor density decreased by 50% 15 h after treatment and recovered to control values after about 250 h. A similar decrease in receptor density and pattern of recovery was found in environmental hypoxia. Neither hypoxia nor treatment with BAAM had a significant effect on the dissociation constant of the radioligand. These results show that cardiac beta adrenoceptor synthesis occurs rather slowly and suggest that alteration of the rate of receptor synthesis in hypoxic states is not a major determinant of reported changes in density. PMID- 2901913 TI - A human protein specific for the immunoglobulin octamer DNA motif contains a functional homeobox domain. AB - The homeobox domain is shared by Drosophila homeotic proteins, yeast mating type proteins, and some functionally uncharacterized mammalian proteins. A lymphoid restricted human protein that binds to the immunoglobulin octamer regulatory motif was shown to contain an amino acid sequence that has 33% amino acid identity with the consensus sequence of the previously cloned homebox domains. This homeobox gene was localized to chromosome 19, thus mapping separately from other human homebox genes. A mutant protein containing amino acid substitutions within a putative helix-turn-helix motif in the homeobox domain did not bind DNA detectably. This human homeobox protein was shown to bind the same DNA sequence as the homeobox domains of the yeast mating type proteins and Drosophila homeotic protein, suggesting that homeobox proteins may have closely related DNA binding characteristics. PMID- 2901914 TI - Induction of suppressor cells to T- and B-cell proliferative responses and immunoglobulin production by monoclonal antibodies recognizing the CD3 T-cell differentiation antigen. AB - Monoclonal antibodies (mAb's) recognizing the CD3 T-cell differentiation antigen induced the generation of suppressor cells. These cells inhibited (1) proliferative responses of human peripheral blood mononuclear cells (PBMC) to PHA and allogeneic cells in mixed leukocyte culture; (2) proliferative responses of purified E-rosette-negative cells to Staphylococcus aureus Cowans I; and (3) de novo immunoglobulin synthesis and secretion in the pokeweed mitogen (PWM)-induced differentiation system. Monoclonal antibodies recognizing other T-cell differentiation antigens (anti-Leu 2a, anti-Leu 3a, and anti-Leu 5) did not induce the generation of suppressor cells, even at very high antibody concentrations. Statistically significant differences were not observed in the ability of the OKT3 and anti-Leu 4 mAb's to induce suppressor cells. Monocytes were not required for the generation of anti-CD3-induced suppressor cells. F(ab')2 fragments of the OKT3 mAb's were equally effective when compared with intact antibody molecules in inducing suppressor cells, although they did not induce proliferative responses. Proliferation was not required for the induction of suppressor cells. Irradiation (2500 rad) of PBMC before incubation with the anti-CD3 mAb did not affect the generation of suppressor cells. Furthermore, anti CD3-induced suppressor cells were radioresistant. Addition of recombinant IL-2 to the cultures of responding cells and suppressor cells did not reverse the suppression. In vitro treatment of anti-CD3-induced suppressor cells with either the OKT4 mAb plus complement or the OKT8 mAb plus complement partially decreased the suppression of proliferative responses of PBMC to PHA or allogeneic cells in mixed lymphocytes culture. However, treatment with both OKT4 and OKT8 mAb's plus complement or the OKT11 mAb plus complement completely abolished the suppression. These results suggest that the suppressor cells are of the T11+T4+T8- and T11+T4 T8+ phenotypes. In other experiments, T4+T8- and T8+T4- cells were isolated from PBMC treated for 48 hr with anti-CD3 mAbs. Both these two populations significantly inhibited proliferative responses of autologous PBMC to PHA and de novo immunoglobulin synthesis and secretion by mixtures of purified T4 and B cells from normal donors, in the PWM-induced differentiation system. These results demonstrate that anti-CD3-induced suppressor cells are of the T4 or T8 phenotype. Treatment of purified T4+T8- and T8+T4- cells with anti-CD3 mAb's resulted in the generation of suppressor cells, suggesting that the precursors of the anti-CD3-induced suppressor cells can belong to either of these two populations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2901915 TI - Modulation of natural killer-mediated lysis by red blood cells. AB - Natural killer (NK)-mediated cytotoxicity is significantly enhanced in the presence of red blood cells (RBC). The enhancement is dose dependent on the number of RBC present and can be induced by autochthonous, allogeneic, or xenogeneic RBC. The enhancement was demonstrated in cytotoxicity against two different NK-sensitive tumor target cell lines, K562 and U937, and by three different assay systems, chromium release, lactate dehydrogenase release, and inhibition of thymidine incorporation. RBC directly enhance the cytotoxic activity of NKH-1/Leu19+ large granular lymphocyte NK cells. Intact RBC have to be present during the cytotoxicity assay to induce the enhancement, which probably occurs at a postbinding, preprogramming phase. The anti-CD2 antibody Leu5 cannot block the enhancement at a concentration inhibitory to lymphocyte rosetting with sheep RBC, suggesting that the enhancement is not induced by interaction through the CD2 antigen. These results indicate that RBC are a potent modulator of NK cytotoxicity and suggest that in vitro NK studies using purified lymphocytes may not always truly reflect NK activity in the blood stream. PMID- 2901916 TI - The role of CD4 in antigen-independent activation of isolated single T lymphocytes. AB - The membrane molecule CD4 (L3T4) is thought to facilitate activation of Class II H-2-restricted T cells by binding to Ia determinants on antigen-presenting cells. Recent reports suggest that CD4 can also contribute to antigen-independent activation by anti-T cell receptor (TCR) antibodies. An assay which measures the secretion of two lymphokines, granulocyte-macrophage colony-stimulating factor and interleukin 3 (IL-3), by single T cells activated with an anti-TCR antibody, F23.1, was used to analyze the effects of anti-CD4 antibodies on antigen independent T cell activation. Single cells of a CD4+F23.1+ clone were micromanipulated into wells to which F23.1 had been immobilized, and their lymphokine secretion was measured 24 hr later. The frequency of lymphokine secreting cells was consistently reduced up to 10-fold in the presence of soluble anti-CD4 antibody (GK1.5) but only up to 2.5-fold by an antibody to the cell adhesion molecule, LFA-1. In both bulk and single-cell cultures, responses to suboptimal concentrations of F23.1 were more susceptible to inhibition by GK1.5 than responses to optimal F23.1. The failure of GK1.5 to inhibit IL-2-stimulated lymphokine synthesis in bulk cultures suggested that CD4 ligation did not deliver a negative signal to the clone. By contrast, when either anti-CD4 or anti-LFA-1 was immobilized on the same surface as F23.1, the frequency of lymphokine secreting cells could be increased up to 10-fold. It is concluded that anti-CD4 antibodies can act directly on the responding T cell to affect TCR-dependent activation, in the absence of interaction with antigen-presenting cells or any other cell type. PMID- 2901917 TI - [Andrologic findings in adolescents with retractile testes]. PMID- 2901918 TI - Identification of structural characteristics of some potential H2-receptor antagonists that determine the interaction with rat hepatic P-450. AB - Several potential H2-receptor antagonists have been tested in vitro, using liver microsomal preparations from untreated rats, in order to study their interaction with P-450. The aim of this investigation was to establish structure-activity relationships for the P-450-inhibition developed by cimetidine and related drugs. Most of the compounds tested demonstrate an inhibitory activity and a binding ability to P-450, via type II (ligand type) binding. Our results strongly indicate that the cyano-guanidine moiety is an essential structural feature for both the inhibition of a ferrocytochrome P-450-metabolic intermediate complex formation occurring during the metabolism of tofenacine, and the binding of the compounds to the heme iron of P-450. The presence of an imidazole group is not necessary for these activities. Furthermore, it is pointed out that the lipophilic character of the cyano-guanidine side chain contributes to the interaction of the test compounds with P-450, since a trend for a parabolic relationship between lipophilicity and inhibitory activity or binding ability is observed. Finally, under the experimental conditions used, no increase of the inhibitory activity of cimetidine on the metabolism of tofenacine and 7 ethylresorufin is observed after preincubation of rat liver microsomes with cimetidine, confirming earlier results in similar studies. PMID- 2901919 TI - Inhibitors of sterol synthesis. Effects of dietary 5 alpha-cholest-8(14)-en-3 beta-ol-15-one on early enzymes in hepatic cholesterol biosynthesis. AB - The effects of dietary administration (0.1% in diet for 8 days) of 5 alpha cholest-8(14)-en-3 beta-ol-15-one on the levels of activity of cytosolic acetoacetyl coenzyme A thiolase, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase, and microsomal HMG-CoA reductase in liver have been studied in male Sprague-Dawley rats. Significant increases in the levels of activity of acetoacetyl-CoA thiolase and of HMG-CoA synthase were observed. The levels of microsomal HMG-CoA reductase activity were increased, relative to pair-fed control animals, in three experiments and increased, relative to ad libitum control animals, in one of three experiments. When compared with other agents for which the primary mode of action is an inhibition of the intestinal absorption of cholesterol, the magnitude of the increases in the levels of hepatic microsomal HMG-CoA reductase activity in the 15-ketosterol-fed rats was considerably smaller. In view of the previously described marked activity of the 15-ketosterol in the inhibition of the intestinal absorption of cholesterol, as well as its known effects in lowering HMG-CoA reductase activity in mammalian cells in culture, it is proposed that the 15-ketosterol may suppress the elevated levels of hepatic microsomal HMG-CoA reductase activity induced by the reduced delivery of cholesterol to liver as a consequence of the inhibition of the intestinal absorption of cholesterol. PMID- 2901921 TI - Growth hormone neuroregulation and its alterations in disease states. PMID- 2901920 TI - Effect of in vitro organic nitrate tolerance on relaxation, cyclic GMP accumulation, and guanylate cyclase activation by glyceryl trinitrate and the enantiomers of isoidide dinitrate. AB - Previously, it was shown that the D enantiomer of isoidide dinitrate was 10-fold more potent than the L enantiomer and 10-fold less potent than glyceryl trinitrate for stimulating cyclic GMP accumulation and relaxation of isolated rat aorta. In the present study, these organic nitrates were tested for their ability to induce tolerance to organic nitrate-induced relaxation, cyclic GMP accumulation, and guanylate cyclase activation in rat aorta in vitro. To compensate for the differences in vasodilator potency, tolerance was induced by incubating isolated rat aorta with concentrations of organic nitrates 1,000-fold greater than the EC50 for relaxation. Under these conditions, the EC50 for relaxation was increased significantly for each organic nitrate and to a similar degree on subsequent reexposure. These data suggest that the potential for inducing in vitro tolerance to relaxation was the same for the three organic nitrates tested. When activation of soluble guanylate cyclase by these compounds was assessed, the enantiomers of isoidide dinitrate were equipotent, but less potent than glyceryl trinitrate, suggesting that the site of enantioselectivity is not guanylate cyclase itself. In blood vessels made tolerant to organic nitrates by pretreatment with glyceryl trinitrate, vasodilator activity, cyclic GMP accumulation, and guanylate cyclase activation were attenuated on reexposure to each organic nitrate. In addition, differences in the potency of the three organic nitrates and the enantioselectivity of isoidide dinitrate for relaxation were abolished in tolerant tissue, whereas the potency difference between glyceryl trinitrate and isoidide dinitrate for activation of guanylate cyclase was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901922 TI - Demonstration of blocking immunoglobulins G, having a heterogeneous behaviour, in sera of patients with Graves' disease: possible coexistence of different autoantibodies directed to the TSH receptor. AB - Previous studies by us and others have shown that Graves' immunoglobulins G (IgGs) behaved as agonists or even antagonists of TSH. In this paper we have looked for the existence of IgG preparations without any thyroid stimulatory activity but able to significantly block the action of TSH in 128 hyperthyroid Graves' patients. The presence of TSH-binding inhibiting antibodies (TBIAb) and that of thyroid stimulating antibodies (TSAb) was evaluated by a radioreceptor assay using solubilized thyroid plasma membranes and by assaying the adenylate cyclase (AC) function of thyroid plasma membranes, respectively. Seventeen IgGs were negative for TSAb but positive for TBIAb in the screening, using only one concentration of IgG. Three kinds of activity were investigated in these IgGs at different doses: (1) TSH-binding inhibiting activity; (2) thyroid AC stimulating activity; and (3) the inhibition of TSH-induced AC stimulation. The results showed that the level of activity was not always dose-dependent. A significant (greater than 20%) inhibition of the TSH-dependent AC stimulation was present in 15 of the 17 IgGs examined: this inhibition was more elevated at lower than at higher doses in two preparations. No significant correlation was found between the three activities. In short, we have been able to demonstrate the existence of 'blocking' antibodies, apparently without any stimulatory activity, in some patients with Graves' disease. The diphasic pattern of the dose-response curves of some IgGs and the lack of correlation between the different activities can be explained by the co-existence in the sera of Graves' patients of different autoantibodies varying in concentration, binding affinity constant and intrinsic biological activity. PMID- 2901923 TI - Responses of plasma oxytocin and arginine vasopressin to nausea induced by apomorphine and ipecacuanha. AB - Apomorphine, a centrally-acting emetic, was administered subcutaneously (50 micrograms/kg) to nine normal subjects (four male, five female; aged 22-36 years) and four patients with idiopathic diabetes insipidus (DI) (one male, three female; aged 24-49 years). In the normal subjects this stimulus caused nausea (and vomiting in seven of nine) with a latency of 9.5 +/- 0.9 min which was followed by a large increase in plasma arginine vasopressin (AVP) concentration (from 0.9 +/- 0.2 pmol/l to 249 +/- 104 pmol/l at 15 min after the onset of symptoms; mean +/- SEM, P less than 0.01). There was a small but significant increase in plasma oxytocin (OXT) concentration (from 1.6 +/- 0.4 pmol/l to 6.2 +/- 3.4 pmol/l; P less than 0.05). Mean arterial pressure (MAP) fell slightly (from 87 +/- 1.9 mm Hg to 71 +/- 4.4 mm Hg; P less than 0.05) 15 min after the onset of nausea; there was no change in blood haematocrit or plasma osmolality and sodium concentration. In the DI patients apomorphine produced nausea (with vomiting in three of four) with a latency of 10.0 +/- 1.4 min but failed to cause an increase in either plasma AVP or OXT. In the DI patients the fall in MAP did not reach statistical significance (83 +/- 4 mm Hg to 71 +/- 11 mm Hg); there was also no change in haematocrit, osmolality or sodium concentration. Ipecacuanha, an emetic with both peripheral and central actions, was administered orally to seven normal subjects (three male, four female; aged 22-36 years) six of whom also underwent apomorphine tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901924 TI - A linkage study of the locus for X-linked Charcot-Marie-Tooth disease. AB - A large family with Charcot-Marie-Tooth disease, showing a probable X-linked incomplete dominant inheritance, was studied by linkage analysis. Results, obtained by the use of X chromosome specific DNA probes of known regional location, suggest that the disease locus is linked to the DXYS1 locus (z = 2.59 at theta = 0.00) and to the DXS14 locus and, places the disease locus between the DXYS1 locus and the DXS14 locus, near the centromere of the X chromosome. Together with the published data, a distance of 13 cM (z = 6.95) was assessed between the disease locus and the DXYS1 locus. PMID- 2901925 TI - Novel HLA class II-associated structural patterns in coeliac disease and type I diabetes. AB - Cell membrane antigens were precipitated from EBV transformed cell lines by a monomorphic DR monoclonal antibody. Three mutually exclusive patterns with two glycoproteins (g25 and g28) that had not been previously identified, were observed. The first, g25+/g28- was found in all cell lines from 40 healthy individuals; a second, g25-/g28- was found in 4/7 coeliac and 2/4 IDDM patients and a third, g25+/g28+ was found in 3/7 coeliac and 1/4 IDDM patients. RFLP analysis with Class II alpha and beta chain probes and several restriction enzymes did not correlate with either of the disease associated patterns. Several possibilities regarding the identity and mode of action of the two polypeptides are described. PMID- 2901926 TI - Evidence of a gene-dosage effect for the glucocorticoid receptor in trisomy 18 mice. AB - The amount of cytosolic glucocorticoid receptor in liver of Ts18, Ts16, and Ts19 vs euploid mouse fetuses was studied after incubation of [3H]dexamethasone with cytosol followed by isoelectric focusing on polyacrylamide gels. In addition, corticosterone concentrations and enzyme activities of alanine aminotransferase and tyrosine aminotransferase were measured in the cytosol of the livers. The amount of glucocorticoid receptor in the cytosol fractions of the livers was always higher in the Ts18 than in the euploid fetuses of the same litter. It was also significantly (P less than 0.0005) higher if pooled data from different litters were analyzed. The ratio of the glucocorticoid receptor in Ts18 vs euploid mice varied between 1.3 and 4.7, with a mean of 2.1. In contrast, the glucocorticoid receptor levels in Ts16 and Ts19 fetuses were not different from the corresponding euploid controls. Comparing the corticosterone levels of the three trisomies tested with the corresponding euploid fetuses, no significant differences were found, indicating that the markedly elevated cytosolic glucocorticoid receptor concentrations in Ts18 were not due to different corticosterone levels. This finding is consistent with the assignment of the glucocorticoid receptor gene to chromosome 18 in the mouse. There was no correlation between glucocorticoid receptor levels and the activity of the two glucocorticoid inducible enzymes tested in the liver of mouse fetuses. PMID- 2901927 TI - Neurochemical characterization of embryonic brain development in trisomy 19 (Ts19) mice: implications of selective deficits observed for abnormal neural development in aneuploidy. AB - In this study, we examined the neurochemical profiles of selected brain regions (cerebral hemispheres, diencephalon/brainstem) in fetal (day 14 to 18 gestation) trisomy 19 (Ts19) mice. The neurochemical characteristics we observed in Ts19 mice were quite different from those we observed previously in Ts16 mice. Choline acetyltransferase (ChAT) activity was reduced significantly in the cerebral hemispheres, but not in the brainstem/diencephalon, of the fetal Ts19 mouse brain, suggesting a selective vulnerability of telencephalic cholinergic neurons. Additionally, the activity of glutamic acid decarboxylase (GAD) was reduced significantly in both hemispheres and diencephalon/brainstem of late gestation Ts19 fetuses, suggesting a selective vulnerability of GABAergic neurons as well. While the levels of catecholaminergic and dopaminergic markers were reduced significantly at late gestational ages, the relative rate of turnover of dopamine (DA), measured by the ratio of DOPAC/DA, was elevated significantly in Ts19 mice. Neither reduction in the thickness of various cellular zones of the cerebral cortex nor reduced cell density of the cerebral cortex accounts for the alterations in neurochemical parameters observed in Ts19 mice. These results suggest that the effects of the triplication of specific genes on the respective chromosomes, rather than a generalized disruption of developmental homeostasis resulting from extra chromosomal material, may produce selective alterations in neurochemical and neuroanatomical markers observed in these two mouse trisomies. PMID- 2901928 TI - Medullary thyroid carcinoma: localization of a mediastinal metastasis with I-131 MIBG. AB - An I-131 metaiodobenzylguanidine (MIBG) scan was performed in a patient with a familial history of multiple endocrine neoplasia (MEN) type 2 and recurrent medullary thyroid carcinoma (MTC). The scan revealed a mediastinal metastasis from her MTC and there was also an imaging pattern of bilateral adreno-medullary hyperplasia. Although the literature indicates that I-131-MIBG scanning is not sufficiently sensitive for the detection of MTC, this procedure has proven to be of value in the management of chosen patients with MEN-associated MTC. PMID- 2901929 TI - Histamine and histamine receptor antagonists in splanchnic compartments in schistosomal portal hypertension. AB - The type and distribution of histamine receptors in the portal circulation were studied in patients with schistosomal hypertension. At laparotomy, the umbilical, left gastric, splenic, and superior mesenteric veins were cannulated. Blood samples were drawn from the systemic circulation and from each vein for histamine assay. Portal pressures were then estimated in each vein. One group of patients received local injections of pheniramine p-aminosalicylate (H1-antagonist) in the four cannulated veins simultaneously. A second group received cimetidine (H2 antagonist), and a third group received a mixture of both drugs. Reestimation of portal pressures indicated that all treatments produced a significant drop in pressure in the four compartments. The highest drop was in the splenic vein after the H1-antagonist and in the gastric vein after the H2-antagonist. The histamine level was somewhat higher in the splenic compartment. These results suggest that both H1- and H2-receptors are present in the four portal compartments, but their distribution may not be uniform. PMID- 2901930 TI - Pharmacokinetic interactions between NSAIDs (indomethacin or sulindac) and H2 receptor antagonists (cimetidine or ranitidine) in human volunteers. AB - The reciprocal effects on pharmacokinetic parameters after a single oral dose of the nonsteroidal antiinflammatory drugs (NSAIDs) indomethacin and sulindac and repeated oral doses of the H2-receptor antagonists cimetidine and ranitidine were determined in two groups of nine healthy subjects each (indomethacin and sulindac groups). Administration of NSAIDs increased the AUC and decreased the oral clearance and apparent volume of distribution of the H2-receptor antagonists without modifying their t1/2. Urinary data and observed modifications in ranitidine and cimetidine metabolites seem to justify a greater increase of H2 receptor antagonist bioavailability with indomethacin (p less than 0.05) than with sulindac (NS). The administration of ranitidine significantly reduced the sulindac volume of distribution without modifying its clearance, which caused an increase in the maximum concentration and a decrease in the t1/2 (p less than 0.05). The effects of cimetidine on the two NSAIDs were more intense than the effect of ranitidine: the decrease in sulindac volume of distribution (p less than 0.02) was accompanied by a significant reduction in sulindac clearance (p less than 0.05). AUC and urinary amounts of sulindac's sulfone metabolite were decreased. These results show that NSAIDs increased the bioavailability of H2 receptor antagonists, and that the latter drugs decrease the volume of distribution of NSAIDs. Furthermore, cimetidine modifies the oxidation metabolism of sulindac. PMID- 2901931 TI - HLA-DR and -DQ DNA genotyping in insulin-dependent diabetes patients in South India. AB - Restriction fragment length polymorphisms (RFLPs) of the HLA-DR beta, -DQ alpha, DQ beta, and -DX alpha genes have been examined in South Indian diabetic patients and controls. The DR. DQ linkage arrangements in South Indians were shown to be different for DR2, DR4, and DRw6 from those commonly seen in Europeans, so that localization of the primary disease-promoting gene in IDDM could be attempted. This study clearly implicates at least one DQ beta allele in the pathogenesis of IDDM. PMID- 2901932 TI - DR beta Taq I restriction fragment length polymorphism (RFLP) associated with insulin dependent diabetes mellitus (IDDM). AB - DNA from insulin-dependent diabetes mellitus patients (IDDM) and healthy control individuals was evaluated using Southern blotting to determine if a disease associated restriction fragment length polymorphism could be found. Using a DR beta-cDNA probe hybridized to Taq I digested genomic DNA, a 3.7 kb fragment was found in all IDDM patients examined (n = 33). Although a high percentage (47 per cent) of the control population also carried the fragment, nearly one-third of those persons were serotyped as DR2. The possible role of gene regulation in the development of IDDM is discussed. PMID- 2901933 TI - Insulin-dependent diabetes mellitus: HLA-DR and -DQ genotyping in three ethnic groups. AB - Human genomic DNA samples from Caucasoids, Chinese, and Koreans of known serological DR antigen specificity were studied for IDDM-associated variation in HLA-DR and -DQ RFLPs (restriction fragment length polymorphisms). Genotyping allowed for accurate assignment of HLA-DR types and in Caucasoids DRw6 as well as DR2 was unequivocally decreased in IDDM. Further, the universality of certain DR2 associated DQ beta subtypes in protection against IDDM was established. HLA-DR3 was found to be increased in IDDM irrespective of whether carried on the B8. DR3 or B18. DR3 haplotype in Caucasoids or on the Bw58. DR3 haplotype in Chinese. These haplotypes have different DR alpha and DX alpha arrangements, so the region of susceptibility is confined to DQ alpha, DQ beta. For HLA-DR4, a 12kb/DQ beta/Bam HI fragment was increased in Caucasoid IDDM, but since this fragment is haplotype specific in Caucasoids and occurs in most healthy DR4- and w9-positive Asians, the 12 kb fragment may be a marker for a DR beta subtype of DR4 associated with IDDM in Caucasoids only. This study has shown the value of ethnic comparisons of HLA-associated diseases, where different linkage disequilibrium relationships have permitted identification of common susceptibility determinants and have provided evidence for some heterogeneity between Caucasoid and Asian populations, in the genetics of IDDM. PMID- 2901934 TI - DQ beta restriction fragment length polymorphism and its relationship to insulin dependent diabetes mellitus. AB - HLA Class II serological and DQ beta restriction fragment length polymorphisms (RFLPs) were compared in 69 patients with insulin-dependent diabetes mellitus (IDDM) and 81 healthy British Caucasoid controls. The backbone of the analysis was formed by two Taq 1 RFLPs of the DQ beta region designated T2 omega and T6. The two are not allelic and can be inherited individually, together on one, or separately on both, parental haplotypes, the latter almost invariably in association with DR4. In our study the frequency in IDDM patients of both T2 omega and T6 together (relative risk for IDDM = 6.4) is similar to that of DR3/DR4 (relative risk for IDDM = 5.4) with an even higher relative risk for IDDM when they are combined, (relative risk = 18 with 95 per cent confidence limits between 14 and 22). We have thus defined DQ beta RFLPs which tightly associate with IDDM individuals with DR4. PMID- 2901936 TI - Fourth histamine antagonist, nizatidine, reaches U.S. market. PMID- 2901935 TI - HLA-DR, -DQ DNA genotyping and T-cell receptor RFLPs in leprosy. AB - HLA-DR and -DQ restriction fragment length polymorphisms (RFLPs) were examined in Melanesian leprosy patients and controls from New Caledonia. This permitted DNA subtyping of DQw1, a broad serological specificity previously implicated in predisposition to lepromatous leprosy. The DQw1c subtype, found in linkage disequilibrium with DR1, w10, w14, and some Pacific Island variants of DRw6 and DRw8, was significantly reduced in leprosy patients. Since the association between HLA-DR genes and leprosy is not strong, some candidate non-MHC genes for leprosy susceptibility were examined also. T-cell receptor -alpha, -beta, and gamma gene RFLPs revealed no germ-line defects or major clonal T-cell expansion in either lepromatous or tuberculoid leprosy patients. The human homologue of the murine Ity locus which determines murine susceptibility to Mycobacterium lepraemurium was sought by examining linkage disequilibrium with RFLPs in the human gamma-crystallin genes, since this gene family forms a syntenic group with isocitrate dehydrogenase-1 in both mouse and man and, in the mouse, this cluster is closely linked to the Ity locus. These RFLPs were not associated with leprosy susceptibility in man. PMID- 2901937 TI - Noninvasive renal diagnostic studies. AB - Traditional methods of noninvasively evaluating patients for renal injury do not accomplish the following tasks: reliably distinguish potentially treatable forms of acute renal failure from acute tubular necrosis; provide a sensitive indicator of early allograft rejection in renal transplant recipients, particularly those in the pediatric age group; provide an early warning of incipient drug-induced nephrotoxicity; or serve as an adequate screening test for renal injury due to exposure to occupational or environmental toxins, especially heavy metals. Because of this, considerable effort has been devoted to the development of assays to satisfy these needs. Three approaches include measurement in the urine of low-molecular-weight plasma proteins such as beta 2-microglobulin; a variety of kidney-derived enzymes, such as L-alanine aminopeptidase and N-acetyl-beta-D glucosaminidase; and specific renal antigens using immunologic detection. The first two of these have not proved to be adequately sensitive or specific, complicated by the frequent loss of activity associated with the physicochemical characteristics of the urine or the presence of pyuria. Despite this, useful information has been obtained. In particular, assays of beta 2-microglobulin urinary excretion and retinol binding protein appear to have clinical utility that should be pursued. Recent experience with a monoclonal antibody-based assay for a unique proximal tubular antigen, the adenosine deaminase binding protein, suggests that a battery of such assays, each directed against an antigen localized to a particular segment of the nephron, may be particularly useful. PMID- 2901938 TI - Mediators of brain edema and secondary brain damage. AB - Progress is our understanding of the roles of vasogenic and cytotoxic brain edema in secondary brain damage can be expected from studies of the ability of biochemical factors to open the blood-brain barrier, derange the microcirculation, and cause cell swelling and necrosis. Mediator compounds are considered to form or to become released in an area of primarily damaged brain (necrosis) and to enter the cerebral parenchyma through the broken blood-brain barrier from the intravascular space. Many biochemical factors must be considered. We suggested three criteria for determining the roles of mediators: a) they must inflict brain tissue damage, b) they must occur in pathologic concentrations or in compartments not normally present, and c) specific inhibition should attenuate secondary brain damage. These requirements are met by the kallikrein-kinin system and by glutamate. In the case of arachidonic acid and its many metabolites, the concept is difficult to test because fatty acids may be active only if not bound to proteins, and therapeutic inhibition might be difficult. A variety of mediators may enhance each other in a cascade manner by various initiating reactions that might be amenable for pharmacologic inhibition. PMID- 2901939 TI - Serum pepsinogen I in familial multiple endocrine neoplasia type I. AB - An increased serum pepsinogen I (PG I) concentration has been reported to be a marker of inherited peptic ulcer disease. Since both the Zollinger-Ellison syndrome and hyperparathyroidism, components of the familial multiple endocrine neoplasia type I syndrome (MEN I), are often associated with peptic ulcer, we have studied serum PG I concentrations in members of six well-defined families with MEN I. Serum PG I concentrations in 20 family members with hyperparathyroidism ranged from 35 to 864 ng/ml compared to 21-92 ng/ml in 16 nonaffected MEN I members. However, serum PG I levels were significantly higher (P less than 0.01) in the hyperparathyroid patients with hypergastrinemia (PGI median 192, range 75-864 ng/ml) than in those with normogastrinemia (PGI median 75, range 35-139 ng/ml). In fact, five of seven patients with hyperparathyroidism and hypergastrinemia compared to only one of 13 hyperparathyroid patients without hypergastrinemia had increased serum PG I levels above 130 ng/ml. We conclude that in the MEN I syndrome, increased serum PG I levels are found in patients with Zollinger-Ellison syndrome but not in hyperparathyroid patients with normogastrinemia and not in nonaffected MEN I members. The results indicate that in familial MEN I, hyperpepsinogenemia I is not inherited as a genetic trait but suggest that the elevated serum PG I levels are secondary to chronic hypergastrinemia. PMID- 2901940 TI - Effect of various prokinetic agents on post Roux-en-Y gastric emptying. Experimental and clinical observations. AB - The effect of various prokinetic drugs was assessed in animals with Roux-en-Y gastrojejunostomy. The agents tested were (1) bethanechol 2.5 mg subcutaneously at 0 min and 30 min postprandially (pp); (2) metoclopramide 20 mg intravenous bolus at 0 min pp; (3) a combination of 1 and 2; (4) oxytocin 5 mg intramuscularly at 0 min and 240 min pp; (5) motilin at 100 ng/kg/hr; or (6) 300 ng/kg/hr continuous intravenous infusion from 0 to 270 min pp. Only bethanechol administration resulted in significantly less gastric retention (65 +/- 6% vs 32 +/- 5% retention at 5 hr). (P less than 0.002). The animal results with parenteral bethanechol were confirmed in humans with chronic delayed gastric emptying following Roux-en-Y gastrojejunostomy, with a decrease in gastric retention on radionuclide scan from 78.5 +/- 5% to 26 +/- 12% at 2 hr pp (P less than 0.01). Initially all patients responded with symptomatic improvement. However, subsequently 3/6 (50%) of patients required total or near total gastrectomy for recurrent symptoms of gastric stasis. Nevertheless, 2/6 (33%) of patients have no further evidence of gastric stasis, and a trial of bethanechol is recommended prior to considering further gastrectomy in patients with the Roux stasis syndrome. PMID- 2901941 TI - Development of neurochemical separation of ON and OFF channels at retinal ganglion cells. AB - Anatomical and physiological segregation of neurons into ON (brightening detector) and OFF (darkening detector) channels in the retina and subsequent visual system ensure the high sensitivity required for contrast detection and spatial discrimination. This segregation is finest at the visual axis. Neurochemically, ON and OFF ganglion cells at the visual axis seem to be distinguished by different inhibitory transmitters but not excitatory transmitters. Microiontophoretic studies of inhibitory transmitters on the retinal ganglion cells in kittens and adult cats suggest that this neurochemical distinction is poor in immature ganglion cells at the visual axis. Initially both ON and OFF cells seem to be supplied by GABAergic, glycinergic, and catecholaminergic amacrine cells, but in adults, ON cells remain supplied only by GABAergic amacrines, while OFF cells are supplied by glycinergic amacrines. Postnatal elimination of multiple inputs and strengthening of the appropriate inputs, as seen in the central nervous system, also seem to occur at the retinal neurotransmitter synapses during development. PMID- 2901942 TI - [Neurochemical induction of the factor of postural asymmetry in the pituitary]. PMID- 2901943 TI - [Recommendations for a stepwise plan of long-term drug therapy in obstructive airway diseases]. PMID- 2901944 TI - [Skin eruptions and paraparesis resembling pedal signs in a pre- viously healthy male subject]. PMID- 2901945 TI - [Acute rheumatoid arthritis--unsolved problems in treatment]. PMID- 2901946 TI - [Alcohol-induced fever and brain symptoms]. PMID- 2901947 TI - A double blind controlled clinical trial of benzoctamin (Tacitin) and imipramine (Tofranil) in the treatment of 'internal heat' and its association symptoms. PMID- 2901948 TI - [Effect of the combined prenatal use of benzodiazepine preparations and alcohol on the functions of the hypophyseal-thyroid system in newborn rat pups]. PMID- 2901949 TI - Impaired suppression of growth hormone release by somatostatin in cultured adenohypophyseal cells of spontaneously diabetic BB/W rats. AB - The effects of the diabetic state on the somatotroph's responsiveness to the secretagogues GRF and (Bu)2-cAMP and to the inhibitor somatostatin (SRIF) were evaluated in enzymatically dissociated rat adenohypophyseal cells in primary monolayer culture. Primary cultures were prepared from pituitary tissue of spontaneously diabetic BB/W rats 23-51 days after the onset of hyperglycemia and glycosuria and of age-matched diabetes-resistant control rats. Dose-related stimulation of GH release by GRF and (Bu)2cAMP did not differ significantly in the two preparations. There was no evidence of abnormal sensitivity to TRH in cultured somatotrophs of diabetic rats. Dose-related suppression of (Bu)2cAMP (0.5 mM)-stimulated GH release by 0.01-10 nM SRIF, on the other hand, was significantly affected by diabetes, as indicated by a parallel shift of the dose response curve to the right and an increase in the IC50 value from 76 +/- 2 to 204 +/- 5 pM (mean +/- SEM; n = 3; P less than 0.001). Maximal suppression by 10 nM SRIF was identical in the two preparations. The degree to which the cultured cells' responsiveness to SRIF was reduced was unrelated to the duration and severity of the diabetic state. Hypothalamic SRIF content did not differ significantly between diabetic and diabetes-resistant rats (186 +/- 12 vs. 178 +/ 10 ng/mg protein). Nevertheless, the SRIF concentration may be elevated in hypophysealportal blood of diabetic rats; we, therefore, examined the effect of prolonged exposure of the cell cultures to SRIF or SMS 201-995 on the subsequent suppression of (Bu)2cAMP-stimulated GH release by SRIF. Addition of either SRIF (10 nM) or SMS 201-995 (5.5 nM) to the culture medium for 4 days significantly increased the IC50 values for SRIF to values similar to those obtained in cultured cells of diabetic rats. We conclude that the somatotrophs of diabetic rats are relatively resistant to SRIF. Since prolonged exposure to SRIF in vitro produced similar resistance, the desensitization in diabetic rats may be due to elevated concentrations of SRIF in hypophyseal-portal blood. This impaired responsiveness to SRIF may contribute to aberrant GH secretion in diabetes. PMID- 2901950 TI - Glutamate stimulates somatostatin release from diencephalic neurons in primary culture. AB - The action of excitatory amino acid agonists on endogenous somatostatin release was examined in primary cultures of rat diencephalic neurons. Increasing concentrations of glutamate stimulated somatostatin release in a dose-dependent manner. Since this effect was decreased by Mg2+, all experiments were performed in Mg2+-free media. We found that excitatory amino acid agonists evoked somatostatin release in the following order of potency: quisqualate greater than glutamate = N-methyl-D-aspartate (NMDA) greater than kainate, as calculated from the dose-response curves. The increase in somatostatin release elicited by glutamate or NMDA was selectively antagonized by DL-2-amino-5-phosphonovaleric acid and by thyenyl-phencyclidine, two specific antagonists of NMDA receptors. The NMDA effect was strongly inhibited: in a competitive manner by APV and in a noncompetitive manner by TCP with IC50 of 90 microM and 0.2 microM, respectively. Glutamate-induced somatostatin release was not blocked by tetrodotoxin (1 microM) suggesting that tetrodotoxin-sensitive sodium-dependent action potentials are not involved in this effect. Our data suggest the presence of functionally active excitatory amino acid receptors in somatostatinergic neurons. Glutamate seems to exert its stimulatory action on somatostatin release essentially through NMDA type receptor sites. PMID- 2901951 TI - Angiotensin-converting enzyme activity in experimental alcoholic fatty liver of the rat. AB - Angiotensin-converting enzyme (ACE) activity was found increased in serum of patients with chronic alcoholism. We studied this enzymatic activity in serum and liver tissue of rats with alcoholic fatty liver due to prolonged intake of ethanol with a liquid diet, according to De Carli and Lieber. Serum and liver ACE activity did not show any significant increase in rats with alcoholic fatty liver when compared with controls, whereas gamma-glutamyltransferase activity exhibited a striking enhancement in serum and liver. Our data suggest that ACE is not an alcohol-induced enzyme in the experimental rat model. PMID- 2901952 TI - Egf binding to its receptor triggers a rapid tyrosine phosphorylation of the erbB 2 protein in the mammary tumor cell line SK-BR-3. AB - The epidermal growth factor receptor (EGF-R) and the erbB-2 proto-oncogene product protein are closely related by their structural homology and their shared enzymatic activity as autophosphorylating tyrosine kinases. We show that in mammary tumor cells (SK-BR-3) EGF causes a rapid increase in tyrosine phosphorylation of the erbB-2 protein. Phosphorylation of erbB-2 does not occur in cells lacking the EGF-R (MDA-MB-453). Phosphorylation of erbB-2 in SK-BR-3 cells is blocked if EGF is prevented from interacting with its receptor by specific monoclonal antibodies. While EGF induces the down-regulation of its receptor in SK-BR-3 cells, EGF has no effect on the stability of the erbB-2 protein. This result suggests that the erbB-2 protein is a substrate of the EGF-R and indicates the possibility of communication between these two proteins early in the signal transduction process. PMID- 2901953 TI - The structure of the human CD2 gene and its expression in transgenic mice. AB - We report the genomic organization of the human CD2 gene and its expression in transgenic mice. A 28.5 kb segment of DNA consisting of 4.5 kb 5' flanking sequences, 15 kb containing the gene's five exons and 9 kb of 3' flanking sequences can direct the expression of the CD2 gene only on thymocytes, circulating T cells and megakaryocytes of the transgenic mice. The expression of each copy of the human CD2 transgene appears to be as high as the endogenous mouse CD2 gene and as high as the expression on the surface of human T lymphocytes, independent of the site of integration and dependent on the copy number of genes that have integrated. PMID- 2901954 TI - The role of localization of bicoid RNA in organizing the anterior pattern of the Drosophila embryo. AB - The organization of the anterior pattern in the Drosophila embryo is mediated by the maternal effect gene bicoid. bcd has been identified in an 8.7-kb genomic fragment by germ line transformants that completely rescue the mutant phenotype. The major transcript of 2.6 kb includes a homeobox with low homology to previously known homeoboxes, a PRD-repeat and a M-repeat. In situ hybridizations reveal that bcd is transcribed in the nurse cells. The mRNA is localized at the anterior tip of oocyte and early embryo until the cellular blastoderm stage. The localization of the transcript requires the function of the maternal effect genes exuperantia and swallow while transcript stability is reduced by functions depending on posterior group genes. PMID- 2901955 TI - Dissection of functional domains of the yeast proton-pumping ATPase by directed mutagenesis. AB - Cation-pumping ATPases characterized by a phosphorylated intermediate have been proposed to contain kinase, phosphatase and transduction domains. Evidence is provided for this model by mutagenesis of critical residues in the proposed domains. The Glu233-Gln mutation blocks the turnover of the intermediate and serves to define the phosphatase domain. Mutations in aspartate residues 534, 560 and 638 alter the nucleotide specificity of the enzyme. These amino acids are therefore part of the ATP binding site. Lys474 seems to be essential for activity in this kinase domain. Finally, mutations in Asp378, the amino acid forming the phosphorylated intermediate, indicate that the formation of a phosphorylated intermediate is not an obligatory step in ATP hydrolysis but is required for coupling this process with proton pumping. PMID- 2901956 TI - The poly(A)-binding protein facilitates in vitro translation of poly(A)-rich mRNA. AB - To investigate the role of the 73-kDa poly(A)-binding protein in protein synthesis, the effect of the addition of homo-polyribonucleotides on the translation of polyadenylated and non-adenylated mRNA was studied in the rabbit reticulocyte lysate. Poly(A) was found to be the most effective polynucleotide in inhibiting duck-globin mRNA translation, whereas it had no effect on the translation of polyribosomal duck-globin mRNP, or on the endogenous synthesis of the rabbit reticulocyte lysate. The translation of poly(A)-free mRNA was not affected by the addition of poly(A). Furthermore, we found that the inhibiting effect of poly(A) can be reversed by addition of purified poly(A)-binding protein. It is thus likely that the 73-kDa poly(A)-binding protein is an essential factor necessary for poly(A)-rich mRNA translation. PMID- 2901957 TI - Effect of vasodilator and inotropic drugs on clinical symptoms and long-term survival in chronic congestive heart failure. AB - The major therapeutic goals in the treatment of congestive heart failure are the relief of symptoms and the prolongation of life, but it remains unclear whether there is a relation between changes in exercise tolerance and alterations in the risk of death. Although all vasodilator and inotropic agents produce short-term haemodynamic benefits, these acute effects do not predict the long-term clinical responses to these drugs. Converting-enzyme inhibitors appear to improve symptoms and survival. A combination of hydralazine and isosorbide dinitrate produces variable effects on exercise tolerance but appears to prolong life. Catecholamines and phosphodiesterase inhibitors may reduce dyspnea and fatigue but adversely affect mortality. Calcium channel blocking drugs may exert deleterious effects on both symptoms and prognosis. alpha-Adrenergic blocking drugs produce no beneficial or adverse effects on clinical status or mortality. Hence, there is no consistent relation between the symptomatic and prognostic effects of drug therapy in patients with chronic heart failure. This variability makes it impossible to predict the effects of any drug on exercise tolerance or survival based on an evaluation of the agent's short-term haemodynamic effects. PMID- 2901958 TI - Receptor-mediated inotropic drugs. AB - Cardiac inotropic activity can be triggered by beta 1-, beta 2- and alpha 1 adrenoreceptors in the heart when stimulated with appropriate agonists. Dopaminergic receptor agonists have little influence on contractile force but the peripheral vasodilatation, improved renal perfusion and enhanced natriuresis mediated by dopaminergic receptor stimulation may improve a condition of congestive heart failure. After a general survey of cardiac beta- and alpha adrenoreceptors and of dopaminergic receptors in the cardiovascular system, the following receptor-mediated inotropic drugs are discussed: isoprenaline, dobutamine, xamoterol, pirbuterol, terbutaline, salbutamol, dopamine, L-dopa and dopexamine. Attention is paid to the receptor profile of these compounds and to the scope and limitations of their application as inotropic drugs in the treatment of congestive heart failure. PMID- 2901959 TI - The influence of long-term anticonvulsant therapy with diphenylhydantoin and carbamazepine on serum gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase. AB - In 110 patients receiving long-term anti-convulsant monotherapy with diphenylhydantoin (DPH) and carbamazepine (CBZ) the serum activities of gamma glutamyltransferase (gamma-GT), aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase (AP) were examined retrospectively. Elevated serum levels of gamma-GT and AP were seen in 91% and 39% of patients receiving DPH therapy compared to 64% and 14% of those receiving CBZ treatment. With all enzymes evaluated increases were more frequent and higher with DPH treatment than with CBZ. Frequency and extent of increased activity of gamma-GT were highly related to daily dosage in both preparations. The proportion of pathological enzyme levels was associated with age in DPH and CBZ therapies but not found to be significant. Sex differences in the frequency of increased enzyme activities could not be demonstrated. The results are discussed in the context of induction of the cytochrome P-450 system. PMID- 2901960 TI - Comparative effects of rifabutin and rifampicin on hepatic microsomal enzyme activity in normal subjects. AB - The comparative enzyme inducing effects of rifabutin and the chemically related drug rifampicin have been investigated in 8 normal subjects. Rifampicin 600 mg daily for 7 days caused considerable shortening of the antipyrine half-life and a marked increase in antipyrine clearance, associated with an increased rate of conversion to norantipyrine and, to a lesser extent, 4-hydroxyantipyrine and 3 hydroxymethylantipyrine. The urinary excretion of 6-beta-hydroxycortisol was also markedly increased, while plasma GGT activity showed only a slight albeit statistically significant elevation. In the same subjects, rifabutin in the proposed therapeutic dosage (300 mg daily) for 7 days also enhanced the metabolic elimination of antipyrine, with preferential stimulation of the demethylation pathway, and increased the excretion of 6-beta-hydroxycortisol, but the magnitude of the effects was significantly less than after rifampicin. No significant change in plasma GGT was seen. The results indicate that, contrary to the findings in animals, rifabutin does have enzyme inducing properties in man, although at the dosages assessed they were considerably less than those of rifampicin. PMID- 2901961 TI - Infection of B lymphocytes by the human immunodeficiency virus and their susceptibility to cytotoxic cells. AB - The T4 molecule (CD4) is an important component of the human immunodeficiency virus (HIV) receptor. As yet, no other component has been demonstrated. We report here that two cell lines, a B lymphoblastoid cell line (Gupta) and a glial cell line (HEB) derived from human embryonal brain tissue, are productively infectable with two distinct isolates of HIV as judged by electron microscopy and immunological and virological studies. These two cell lines do not display detectable surface CD4 glycoprotein. However, using S1 nuclease analysis, we have found that both cell lines do express low levels of CD4 mRNA. Neither of them produced syncytia formation upon HIV infection, a recognized feature of HIV infected cells strongly expressing the CD4 glycoprotein. It is conceivable that the CD4 mRNA is translated, resulting in meager surface expression of CD4 molecules undetectable by conventional techniques. Therefore, infection with HIV may be one of the most sensitive methods of demonstrating low levels of CD4 expression by human cells. Furthermore, HIV-infected Gupta cells have here been shown to be more susceptible to the lytic activity of natural killer (NK) cells than their uninfected counterparts. These phenomena may be important for pathogenesis of HIV-associated disorders. PMID- 2901962 TI - Characterization of T cell receptors on resident murine dendritic epidermal T cells. AB - Cell lines derived from Thy-1+ dendritic epidermal cells (Thy-1+DEC) display a marked heterogeneity in T cell receptor (TcR) expression including CD3-associated alpha/beta, C gamma 1/delta or C gamma 2/delta and C gamma 4/delta TcR. In order to investigate whether this heterogeneity is primarily imposed by in vitro culture conditions or, alternatively, is already present within the epidermis, we studied TcR expression by Thy-1+DEC in situ and on freshly isolated epidermal cell suspensions greatly enriched for Thy-1+DEC. Immunolabeling experiments showed that resident Thy-1+DEC are CD45+, Thy-1+, CD3+, TcR V beta 8-, CD5-, CD4- CD8-, CD25- lymphocytes. Immunoprecipitation of lysates from 125I-surface-labeled Thy-1+DEC-enriched epidermal cells with anti-CD3 epsilon, anti-C gamma 1,2,3 and anti-C gamma 4 antibodies, respectively, and subsequent analysis of the precipitates by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed only CD3-associated 35 kDa/45 kDa gamma/delta heterodimers. The demonstration of TcR heterodimers on resident Thy-1+DEC strongly implies that these cells are functional T cells. The selective expression of C gamma 1/delta (C57BL/6) and C gamma 1/delta or C gamma 2/delta (C3H/He) TcR makes these cells useful for the study of gamma/delta TcR function. PMID- 2901963 TI - Thymocyte clones from 14-day mouse embryos. II. Transcription of T3 gamma gene may precede rearrangement of TcR delta and expression of T3 delta, T3 epsilon and T11 genes. AB - We have studied the state of TcR delta gene and the expression of T3 delta, T3 epsilon, T3 gamma and T11 (CD2) genes in the fetal thymocyte (FT) clones A2, G15, H5, E10, D5, H12, F1 and D11 obtained from a 14-day B10.BR mouse fetal thymus. The eight FT clones contain the TcR delta gene in the germ-line configuration as determined by Southern blot analysis. With the exception of clones E10 and D5, the other six FT clones express normal sized transcripts for T3 gamma gene and none of the eight FT clones produced detectable RNA transcripts for T3 delta, T3 epsilon and T11 genes as assessed by Northern blot analysis. Together with our previous work showing that all eight FT clones contain the TcR gamma and the TcR beta gene clusters in the germ-line configuration, the data indicate that the FT clones represent the earliest stage of T cell development identified within the thymus. Our results provide evidence that (a) the T3 gamma gene is the first of the genes that encode components of a TcR/T3 complex to be expressed in ontogeny within the thymus; (b) the T3 (delta, epsilon, gamma) genes are switched on asynchronously and their expression must be differentially regulated, and (c) the T11 gene product may not be involved in early stages of T cell development within the thymus. PMID- 2901964 TI - Cyclic AMP-mediated alteration of the CD2 activation process in human T lymphocytes. Preferential inhibition of the phosphoinositide cycle-related transduction pathway. AB - Activation of human T lymphocytes via the CD2 molecule produces an enhanced turnover of phosphatidylinositol (PI) cycle-related phospholipids accompanied by the increased production of diacylglycerol (DG) and phosphorylated derivatives of inositol (IP). In this report we demonstrate that increased levels of intracellular cyclic AMP induced in human T lymphocytes by prostaglandin E2 or dibutyryl cAMP antagonize these early biochemical events of the CD2 activation process. Thus, a substantial inhibition of the CD2-induced increase in 32P phosphatidic acid and 32P-PI values is observed. In parallel, both the DG production and the IP release triggered by the CD2 signal are strongly reduced contrasting with an almost conserved Ca2+ response. We also report here that cAMP does inhibit the CD2-induced proliferation in a dose-dependent manner while the proliferation generated independently of DG and IP production by a combination of Ca2+ ionophore A23187 and 12-O-tetradecanoylphorbol 13-acetate is not affected. These results therefore suggest that (a) intracellular cAMP levels may participate in the regulation of the PI cycle-related transduction pathway involved in the activation process of human T lymphocytes via the CD2 molecule; (b) the observed cAMP-mediated functional inhibitory effects are mainly related to an alteration of this cellular transduction signal; and (c) considering the putative critical second messenger role in the T cell proliferative response of DG and IP, respectively thought to activate the protein kinase C and to raise the intracellular free Ca2+, the lowering of DG production may be the key event responsible for this cAMP-mediated effect. PMID- 2901965 TI - Low doses of interleukin 2 induce bystander cell lysis by antigen-specific CD4+ inflammatory T cell clones in short-term assay. AB - The effect of recombinant interleukin 2 (rIL2) and interferon-gamma (IFN-gamma) on the cytolytic activity of a CD4+ class II major histocompatibility complex ovalbumin (OVA)-specific murine clone called 5.8.6 was examined. Low doses of IL2 (0.1-1.0 U/ml) induce clone 5.8.6 to kill in an antigen-independent fashion in short-term 51Cr-release and 3H-release assays (6-12 h). Targets killed by 5.8.6 cells include P815, YAC-1 and B lymphoma cells. IFN-gamma, alone or in combination with IL2, has no effect. 5.8.6 and similar inflammatory CD4+ T cell clones have been shown to lyse bystander target cells in the presence of a specific stimulator target. We propose that killing of bystander targets by clone 5.6.8 is due to nonspecific cytolytic activity induced by the clone's own IL2 secreted in response to recognition of the specific target. PMID- 2901966 TI - Evidence that protein kinase C differentially regulates the human T lymphocyte CD2 and CD3 surface antigens. AB - The purpose of the present study was to explore the effects of protein kinase C (PKC) stimulation on two cell surface receptors that regulate T cell growth: the T cell antigen receptor/CD3 complex and the CD2 antigen. The data show that PKC differentially regulates the expression and functions of CD2 and CD3 molecules. Thus, activation of PKC induced a decrease in cell surface levels of CD3 molecules but an increase in the expression of CD2 antigens. Additionally, prolonged stimulation of PKC inhibited subsequent T cell activation via CD3 but promoted activation via CD2 molecules. These results suggest that the CD2 cellular activation pathway would be preferred in T cells which have been exposed to stimulators of PKC. The molecular basis for the regulatory effects of PKC on CD3 and CD2 molecules and its physiological significance are discussed. PMID- 2901967 TI - Clonal analysis of human T lymphocytes infiltrating the liver in chronic active hepatitis B and primary biliary cirrhosis. AB - Human T lymphocytes infiltrating the liver in chronic active hepatitis B (CAH-B) and primary biliary cirrhosis were isolated from liver biopsy cores, cloned by limiting dilution technique and expanded in vitro. Phenotypic and functional analysis demonstrates that this tissue infiltrate represents a heterogeneous cell population. However, when compared to peripheral blood lymphocytes of the same patients, a marked enrichment for T8+ cytotoxic T cells was found to exist at a local site in both types of chronic liver disease. These data provide support for the notion that liver cell injury in CAH-B and PBC may be mediated by a common immunologic mechanism likely executed by cells of the T lineage. PMID- 2901968 TI - Analysis of human lymphocyte protein expression. I. Identification of subpopulation markers by two-dimensional polyacrylamide gel electrophoresis. AB - This study provides new knowledge on the changes in protein expression that differentiate the functionally and phenotypically different cells of the human immune system. Purification by flow cytometry of normal lymphocytes (both T and B cells), monocytes and granulocytes, combined with high-resolution two-dimensional polyacrylamide gel electrophoresis, revealed reproducible qualitative and quantitative changes between these cell populations. Characteristic profiles of marker proteins for each cell type were identified. Determination of markers for T lymphocyte subpopulations was achieved by the comparative analysis of normal T cells separated on the basis of CD4 and CD8 expression in combination with the analysis of cells from patients with T cell chronic lymphocyte leukemia. These results suggest that the modulation or regulation of proteins is very strictly controlled in lymphoid differentiation, and that several quantitative and a few qualitative differences can give rise to completely different phenotypes. Thus, instead of detecting numerous random differences among lymphocyte protein patterns, rather stringent regulation of protein expression in each subpopulation was found. PMID- 2901969 TI - Early metabolic and endocrine effects of perorally administered beta-adrenoceptor agonists in calves. AB - Early metabolic and endocrine changes in calves in response to two beta adrenoceptor agonists in the absence and presence of the beta-adrenoceptor blocking agent propranolol have been studied in calves. The agonists were administered p.o. with milk in different amounts, whereas propranolol was infused i.v. for 10 h. Respiration volume, O2 consumption, CO2 production, respiratory quotient, blood glucose, lactate, non-esterified fatty acids and insulin transiently increased within 2-4 h in a dose-dependent manner, whereas glucagon, adrenaline, noradrenaline, triiodothyronine, urea, albumin and protein did not change significantly. Propranolol completely inhibited the effects on glucose, lactate, non-esterified fatty acids and insulin. Six hours after the administration of the beta-adrenoceptor agonists, the glucose clearance rates following i.v. infusion of glucose were markedly reduced and the glucose decrements in response to an i.v. injection of insulin were much smaller than in the absence of the beta-adrenoceptor agonists. The metabolic changes demonstrate an enhanced glycogenolysis and fat mobilisation, an increased metabolic rate and the development of insulin resistance within 6 h after the administration of the beta-adrenoceptor agonists. PMID- 2901970 TI - Bradykinin antagonism: differentiation between peptide antagonists and antiinflammatory agents. AB - Three non-steroidal antiinflammatory agents were tested for their ability to antagonize bradykinin in the rabbit jugular vein, the dog carotid artery and the guinea pig trachea. The new agents were compared with indomethacin, as well as with [Thi5,8,D-Phe7] bradykinin and [Thi6,9,D-Phe8] kallidin, two B2 receptor antagonists. The antiinflammatory agents did not alter the effects of bradykinin in the two isolated vessels while they completely blocked (like indomethacin) the relaxation induced by bradykinin in guinea pig tracheae contracted with histamine or neurokinin A. The two bradykinin antagonists significantly reduced the contractions of the rabbit jugular vein and the relaxation of the dog carotid artery (with endothelium) in response to bradykinin: these antagonists were however inactive against bradykinin in the guinea pig trachea. The data now reported suggest that B2 receptors are involved in the opposite (stimulant or inhibitor) effects of the kinins in the two isolated vessels while the relaxation of the guinea pig trachea is a prostaglandin-dependent phenomenon which does not involve the activation of B1 or B2 receptors. PMID- 2901971 TI - Blockade of brain dopamine receptors antagonizes the anti-immobility effect of MIF-1 and Tyr-MIF-1 in rats. AB - Previous studies have shown effects of MIF-1 (prolyl-leucyl-glycinamide) and Tyr MIF-1 (tyrosyl-prolyl-leucyl-glycinamide) in animal models of depression and also effects on dopaminergic function. These observations prompted us to examine whether the effects of the two peptides in the behavioral 'despair' test were modulated by dopamine antagonists. MIF-1 and Tyr-MIF-1, at the small dose of 0.01 mg/kg i.p. (24, 5 and 1 h before the test), produced a significant anti immobility effect. This effect was antagonized by a single injection of either haloperidol or sulpiride, two dopamine receptor blockers. The same low dose of the tricyclic antidepressant desipramine was without significant effect in this test. The results indicate that Tyr-MIF-1, like MIF-1, is active in the behavioral despair test for antidepressants and that at least some of the CNS actions of these peptides are mediated by dopamine receptors. PMID- 2901972 TI - Kynurenate and FG9041 have both competitive and non-competitive antagonist actions at excitatory amino acid receptors. AB - The antagonist profile of kynurenate and FG9041 have been characterised in a modified preparation of the baby rat hemisected spinal cord. Both kynurenate and FG9041 were competitive antagonists of responses to kainate and AMPA, although neither antagonist was selective for kainate versus AMPA. In contrast, both antagonists produced an apparent unsurmountable antagonism of responses to NMDA, indicating a different mode of action at the NMDA receptor. PMID- 2901973 TI - Similar effects of diazepam and the 5-HT3 receptor antagonist ICS 205-930 on place aversion conditioning. AB - The anti-anxiety effect of diazepam and the antagonist of 5-HT3 receptors, ICS 205-930, was studied with a conditioned place aversion test design. The results showed that when one of two distinctive and previously preferred compartments was associated with an inescapable footshock, the control animals avoided that compartment in the post-conditioning test. Both diazepam (1-4 mg/kg i.p.) and ICS 205-930 (0.125-1.0 mg/kg i.p.), given before the post-conditioning test, increased in a dose-dependent manner the amount of time spent by the animals in the compartment conditioned to footshock. The results support the view that central 5-HT3 receptors may be involved in the control of anxiety. PMID- 2901974 TI - 5-Methyl-urapidil discriminates between subtypes of the alpha 1-adrenoceptor. AB - The affinity of 5-methyl-urapidil for alpha 1-adrenoceptors was determined from the inhibition of [3H]prazosin binding on membrane of different rat tissues. In hippocampus, vas deferens and heart 5-methyl-urapidil displaced [3H]prazosin in a biphasic manner with mean pKI values between 9.1 and 9.4 for the high-affinity site and 7.2 to 7.8 for the low-affinity site. Only the low affinity site was found in spleen and liver. At present, 5-methyl-urapidil is the antagonist which most clearly discriminates between alpha 1-adrenoceptor subtypes. PMID- 2901975 TI - Behavioral effects of acute and chronic buspirone. AB - The effects of buspirone were studied in squirrel monkeys trained to lever-press under a fixed-interval schedule involving suppressed responding. Buspirone (0.01 0.1 mg/kg) generally did not increase rates of suppressed responding. Buspirone (0.01-0.1 mg/kg) generally did not increase rates of suppressed responding; 0.3 mg/kg of buspirone decreased rate. In comparison, diazepam (0.1-1.0 mg/kg) and CL 218872 (0.3-3.0 mg/kg) increased responding. Additionally, the effects of buspirone (0.01-0.3 mg/kg) were unchanged over a 12-day period of daily administration. The results show that buspirone has effects on schedule controlled behavior of squirrel monkeys that differ from those of typical anxiolytic drugs. PMID- 2901976 TI - Regulation of CAD gene expression in mouse fibroblasts during the transition from the resting to the growing state. AB - We have analyzed the steady-state levels of CAD mRNA and ATCase activity in BALB/c 3T3 mouse fibroblasts at quiescence and at various time points following the initiation of serum stimulation. Steady-state levels of CAD mRNA in 3T3 cells following 12 h of serum stimulation increased 10-fold over levels measured at quiescence. In contrast to the observed increase in steady-state levels of CAD mRNA, its rate of transcription increased only 3-fold, suggesting that the expression of CAD gene in these cells is regulated at both the transcriptional and post-transcriptional levels, to a major extent by the latter. These increases in CAD mRNA in serum-stimulated cells were followed by parallel increases in ATCase activity as well. When comparing DNA synthesis [( 3H]thymidine uptake) to the accumulation of CAD mRNA and ATCase activity, it was observed that this accumulation occurred during the mid- to late-G1 phase of the cell cycle. These results suggest that the expression of CAD gene is cell growth dependent and may be a prerequisite to DNA synthesis. PMID- 2901977 TI - Dopamine and serotonin in cat retina: electroretinography and histology. AB - Anatomical structures of the cat retina were related to functional changes induced by the application of dopaminergic and serotonergic substances. We report on the contribution of dopaminergic and serotonin accumulating retinal neurones to retinal activity as reflected by the electroretinogram. The effect of dopaminergic neurones was investigated by the application of the neurotoxin 6 hydroxy-dopamine (6-OHDA) which is known to destroy dopaminergic neurones, and injections of either serotonin (5-HT) or the analogue 5,6-dihydroxy-tryptamine (5,6-DHT) were used to monitor the effects of indoleamines. In control experiments aminophosphonobutyric acid (APB), an agonist of glutamate transmission, was injected. Conventional immunohistochemical methods identified dopaminergic and serotonin accumulating neurones, and the electrophysiological data obtained from the same animals were related to the anatomical structures influenced by the respective substances. Destruction of dopaminergic amacrine cells by 6-OHDA increased the ERG b-wave amplitude. Accumulation of indoleamines by certain amacrine cells also caused an increase of the ERG b-wave. However, intra-vitreal injection of APB completely blocked the b-wave. The data show that ERG mass responses can be used to monitor transmitter-specific effects on retinal circuitry. PMID- 2901978 TI - Graft-derived recovery from 6-OHDA lesions: specificity of ventral mesencephalic graft tissues. AB - A series of experiments have been conducted to assess the specificity of recovery from motor asymmetries that is provided by dopamine-rich grafts in the neostriatum of rats with unilateral dopamine-depleting lesions produced by injection of 6-hydroxydopamine into the ascending nigrostriatal pathway. Grafts of embryonic tissue taken from the substantia nigra (rich in dopamine neurons could provide a complete recovery of methamphetamine-induced rotation and a partial recovery of apomorphine-induced rotation, whereas no recovery was seen in rats with grafts of tissue rich in another monoamine (serotonin, dissected from the mesencephalic raphe) or of tissue appropriate to the target (dissected from the striatal eminence). 6-Hydroxydopamine lesions of dopamine cells in the grafts of recovered animals reinstated the initial lesion-induced asymmetry. Dopamine rich grafts implanted into the intact neostriatum did not induce any "supernormal" asymmetry in the rats, but did provide a "prophylactic" protection against subsequent lesions of the intrinsic ipsilateral dopamine nigrostriatal system. Post-mortem biochemical assays indicated that the extent of dopamine depletion in the neostriatum of lesioned rats correlated highly with both methamphetamine and apomorphine turning rates. Similarly, both drug rotation tests correlated significantly with the extent of dopamine restoration in the dorsal striatum of rats with dopamine-rich grafts, the correlation being significantly higher for the methamphetamine than for the apomorphine test. PMID- 2901980 TI - Trichomonas vaginalis: characterization of its glutamate dehydrogenase. AB - An NADP-linked glutamate dehydrogenase (EC 1.4.1.4) was found in the soluble fraction of Trichomonas vaginalis. Its molecular weight was about 230,000 (gel filtration). The enzyme, partially purified by diafiltration and hydroxyapatite column chromatography, was heat stable (1 hr at 57 C). It catalyzed both the amination of alpha-ketoglutarate (mean Km 0.6 mM) and the deamination of glutamate (mean Km 1.2 mM) The optimum pH of the amination reaction was 6.7, and that of the deamination reaction was 8. Glutamate was a competitive inhibitor of the amination reaction (mean Ki 5.6 mM) and alpha-ketoglutarate a partially competitive inhibitor of the deamination reaction (mean Ki 0.45 mM). Both guanosine and inosine diphosphates (1 mM) increased the Km alpha-ketoglutarate fivefold (mean Ki's 0.3 and 0.4 mM, respectively). Guanosine diphosphate reduced the Km glutamate 40%. Adenosine di- and triphosphate (1 mM) were ineffective. Because the amination reaction displayed substrate inhibition, guanosine and inosine diphosphates were potent natural inhibitors, and ammonia released by deamination reactions would tend to raise pH (amination operative at acid pH), we hypothesize that the deamination reaction may predominate in the living organism. PMID- 2901979 TI - Lesion-induced vestibular plasticity in the frog: are N-methyl-D-aspartate receptors involved? AB - The synaptic excitation of central vestibular neurons in the isolated superfused brainstem of chronic hemilabyrinthectomized (HL) frogs and of controls was studied electrophysiologically and pharmacologically. Central vestibular neurons were excited either through vestibular afferent fibers or through the vestibular commissural pathway by means of electrical stimulation of the ipsilateral or the contralateral VIIIth nerve. In chronic HL frogs, commissural field potential amplitudes were on the average larger than those of intact frogs and the shape parameters of intracellularly recorded commissural EPSPs of chronic animals were on the average shifted towards those of vestibular afferent EPSPs. In control frogs, vestibular afferent EPSPs were generated independently from N-methyl-D aspartate (NMDA) receptors, whereas commissural EPSPs exhibited a delayed NMDA receptor mediated component. Commissural EPSPs of HL frogs exhibited a NMDA receptor mediated component as well. The size of this EPSP component was larger when the time to peak of the EPSP was longer. EPSPs with similar rise times exhibited NMDA mediated components of similar size, irrespective of whether they originated from chronic animals or controls. The tendency of these EPSPs towards shorter rise times in chronic animals was paralleled by a similar decrease of the relative size of their NMDA receptor mediated component. It is concluded that the increased synaptic efficacy of commissural fibers observed in chronic HL frogs does not result from an increased NMDA receptor component. PMID- 2901981 TI - Entamoeba histolytica: cell cycle and nuclear division. AB - The cell cycle of Entamoeba histolytica, the duration of its phases, and the details of the nuclear division stages are described in this paper. Trophozoites from clone L-6, strain HM1:IMSS, were synchronized by colchicine. Synchrony was observed immediately after treatment and cultures remained synchronous for at least three replicative cycles with synchrony indexes between 13 and 15 hr. The stages of nuclear division were studied by light and electron microscopy. Four stages of the nuclear division were defined: prophase, early anaphase, late anaphase, and telophase. No metaphase stage was observed by light or electron microscopy. One of the first events in the nuclear division was the presence of a bud close to the juxtanuclear body, which grew to a daughter nucleus. The karyosome and the nuclear membrane remained throughout the mitotic process. Bundles of intranuclear microtubules were observed forming a "V" from the center of the nucleus to one of the poles, and associated with them, 12 to 16 chromosomes-like structures appeared. The results of these studies strongly suggest that division of E. histolytica involved a pleuromitotic process which is carried out in about 120 min. PMID- 2901982 TI - Effects of buthionine sulfoximine on the development of ozone-induced pulmonary fibrosis. AB - The capacity of reduced glutathione (GSH) to protect lung tissue against ozone induced pulmonary fibrosis was investigated. Male B6C3F1 mice were exposed to 0, 0.2, 0.5, and 1.0 ppm ozone for 23 hr/day for 14 days. During exposures and/or for a period of 90 days after exposures, subgroups of mice at each exposure level were given drinking water containing 30 mM L-buthionine-S,R-sulfoximine (BSO) to lower in vivo levels of GSH. These BSO treatments reduced blood glutamylcysteine synthetase (GCS) activity (regulatory enzyme for GSH biosynthesis) and lung nonprotein sulfhydryl (NPSH) levels in nonexposed animals by approximately half. In contrast, ozone exposures increased blood GCS activity and lung NPSH levels in a concentration-dependent manner, with smaller increases in the BSO-treated mice. Immediately after exposures, an ozone-related inflammatory response was seen in lungs, but no histopathological signs of developing fibrosis were evident. Ninety days later, mice exposed to 1 ppm ozone and not treated with BSO had modest evidence of pulmonary fibrosis. Mice exposed to 1 ppm ozone and treated with BSO during this post-exposure period (regardless of BSO treatment during exposures) showed histopathological evidence of exacerbated pulmonary fibrosis, compared to similarly exposed mice not treated with BSO postexposure. These results indicated that interference with the body's normal defense mechanisms against oxidant damage, including suppression of GSH biosynthesis, exacerbates the subsequent development of pulmonary fibrosis. PMID- 2901983 TI - Identification of nucleus-encoded F0I protein of bovine heart mitochondrial H+ ATPase as a functional part of the F0 moiety. AB - The F0I protein of apparent Mr 27,000, previously characterized [(1988) Eur. J. Biochem. 173, 1-8] as a genuine component of bovine heart F0, has been sequenced and shown to be identical with the nucleus encoded 24,668 Da protein characterized earlier [(1987) J. Mol. Biol. 197, 89-100]. It is directly shown by proteolytic cleavage and reconstitution experiments that this protein, denoted here as PVP from the single-letter codes of the last three residues of the N terminus, is involved in proton conduction by F0 and in its sensitivity to oligomycin. PMID- 2901984 TI - Identification of a Glu greater than Lys substitution in the activation segment of human pepsinogen A-3 and -5 isozymogens by peptide mapping using endoproteinase Lys-C. AB - The isozymogens PGA-3 and PGA-5 of human pepsinogen A were digested with endoproteinase Lys-C. The peptides were separated by reverse-phase HPLC. PGA-5 showed a peak strongly absorbing at 254 nm absent in PGA-3. Analysis of amino acid composition using the Pico-Tag methodology combined with DABITC-sequencing reveals the sequence Tyr-Phe-Pro-Gln-Trp-Lys (peptide 37-43 of the activation segment). This confirms a study at the DNA level by our group [16] suggesting a Glu greater than Lys mutation at position 43 in the activation segment of PGA-5. Furthermore, it is proposed that the number of genetic variants of PGA is higher than is actually seen by electrophoresis. PMID- 2901985 TI - A nuclear yeast gene (GCY) encodes a polypeptide with high homology to a vertebrate eye lens protein. AB - We describe here the nuclear gene for a yeast protein showing unexpectedly high homology with mammalian aldo/keto reductases as well as with p-crystallin, one of the prominent proteins of the frog eye lens. Although it could be proven that the gene occurs as a single copy in the haploid yeast genome, replacement of the intact by a disrupted, nonfunctional allele led to no obvious phenotype, indicating that the gene is dispensable. The gene was assigned to chromosome XV. It is transcribed in vivo into an mRNA of about 1300 bases with a coding capacity for a protein of 312 amino acids (estimated Mr 35,000). PMID- 2901986 TI - Molecular cloning and sequence analysis of cDNA encoding human kidney D-amino acid oxidase. AB - cDNA clones encoding D-amino acid oxidase were isolated from a human kidney cDNA library by hybridization with cDNA for the pig enzyme. The cDNA insert of 2.0 kilobase pairs long provided coding information for a protein consisting of 347 amino acids. The molecular mass of the enzyme was calculated to be 39,410 Da. The amino acid sequence similarity between the pig and human enzymes is 84.4%, and among the active site residues proposed from chemical modification studies, methionine-110 of the pig enzyme was replaced by threonine. Northern blot analysis confirmed the expression of an mRNA of 2.0 kilobases encoding the D amino acid oxidase in human kidney. PMID- 2901987 TI - Cloning and sequencing of a Clostridium perfringens sialidase gene. AB - Escherichia coli was transformed with pUC vectors containing Sau3A restriction fragments (RF) of Clostridium perfringens DNA. Two clones expressed sialidase activity when assayed with the fluorogenic substrate 4-methylumbelliferyl-alpha-D N-acetylneuraminic acid. A synthetic oligonucleotide representing the N-terminus of the expressed enzyme hybridized with the clostridial insert and with a corresponding 2.1 kb Sau3A RF of the C. perfringens genome. The insert reduced to 1.4 kb, which still encoded active sialidase, has been sequenced. The structural gene encodes 382 amino acids representing an Mr of 42770. A hydrophobic leader sequence is absent. Upstream from the initiation codon ATG, a GA-rich region is found and considered as the Shine-Dalgarno sequence. Homology with the N-terminus of the Vibrio cholerae sialidase gene and with viral sialidase sequences was not found. PMID- 2901988 TI - Unprecedented lysyloxidase activity of Pichia pastoris benzylamine oxidase. AB - Benzylamine oxidase (EC 1.4.3.6) from the yeast Pichia pastoris is a 106 kDa quinoprotein containing one copper atom per molecule. It has a broad substrate specificity ranging from butylamine to peptidyl lysine in collagen and elastin. The kinetic data obtained using lysine-containing model peptides as substrates indicate an astonishing similarity to mammalian lysyloxidase. This similarity is further supported by the inhibition of both enzymes with beta-aminopropionitrile. PMID- 2901989 TI - Effect of site-specific mutagenesis of tyrosine-55, methionine-110 and histidine 217 in porcine kidney D-amino acid oxidase on its catalytic function. AB - To assess the contributions of Tyr-55, Met-110 and His-217 in porcine kidney D amino acid oxidase (EC 1.4.3.3, DAO) to its catalytic function, we constructed three mutant cDNAs coding for the enzymes possessing Phe-55, Leu-110 and Leu-217 by site-specific mutagenesis. The mutant and wild type cDNAs could be expressed in vitro with similar efficiency. The three mutant enzymes thus synthesized showed catalytic activities comparable to that of the wild type oxidase. It is concluded that Tyr-55, Met-110 and His-217 are not directly involved in the catalytic function. PMID- 2901990 TI - Complete amino acid sequence of human intestinal aminopeptidase N as deduced from cloned cDNA. AB - The complete primary structure (967 amino acids) of an intestinal human aminopeptidase N (EC 3.4.11.2) was deduced from the sequence of a cDNA clone. Aminopeptidase N is anchored to the microvillar membrane via an uncleaved signal for membrane insertion. A domain constituting amino acid 250-555 positioned within the catalytic domain shows very clear homology to E. coli aminopeptidase N and contains Zn2+ ligands. Therefore these residues are part of the active site. However, no homology of the anchor/junctional peptide domain is found suggesting that the juxta- and intra-membraneous parts of the molecule have been added/preserved during development. It is speculated that this part carries the apical address. PMID- 2901991 TI - Etoxadrol-meta-isothiocyanate: a potent, enantioselective, electrophilic affinity ligand for the phencyclidine-binding site. AB - Etoxadrol-meta-isothiocyanate (2S,4S,6S-2-ethyl-2-(3-isothiocyanatophenyl)-2 piperidyl)1,3-dioxolane, 4a) has been synthesized and characterized as an irreversible ligand for the phencyclidine (PCP)-binding site. It is the first chiral electrophilic affinity ligand for this site to have been described. This affinity ligand is based upon etoxadrol, a 1,3-dioxolane known to have PCP-like effects in vivo and in vitro. Etoxadrol-meta-isothiocyanate was found to be four five times more potent in vitro than metaphit (1-[1-(3- isothiocyanatophenyl)cyclohexyl]piperidine), the only previously known electrophilic affinity ligand for the PCP-binding site. The binding was shown to be highly enantioselective for etoxadrol-meta-isothiocyanate (4a). The 2R,4R,6R enantiomer of 4a was essentially inactive. The ability of the 2S,4S,6S-enantiomer (4a) to interact with the benzodiazepine, muscarinic, and mu opioid receptor systems was also examined, and it was found not to interact with these receptor systems. It seems likely that 4a will prove to be a valuable tool in the study of structure and function of the PCP-binding site. PMID- 2901992 TI - Expression of four types of human tyrosine hydroxylase in COS cells. AB - Alternative splicing from a single gene produces four kinds of human tyrosine hydroxylase (types 1-4), which have structural diversity only in the N-terminal region. We attempted expression of the type 1-4 enzymes in COS cells and performed kinetic analyses. All had enzymatic activities. The Km values of the four types for L-tyrosine and 6-methyl-5,6,7,8-tetrahydropteridine were similar, although their relative homospecific activities were clearly different. The type 1 enzyme displayed the highest activity. PMID- 2901993 TI - Comparison of the new antihistamine acrivastine (BW 825C) versus cyproheptadine in the treatment of idiopathic cold urticaria. AB - A double-blind, crossover trial with a new triprolidine derivative, acrivastine (BW 825C; 8 mg 3 times daily), cyproheptadine (4 mg 3 times daily) and placebo was carried out in 18 patients suffering from idiopathic cold urticaria. Acrivastine and cyproheptadine significantly (p less than 0.01) reduced weal areas following ice cube challenge when compared to placebo. Acrivastine was found to be significantly more effective (p less than 0.01) than cyproheptadine in reducing weal areas. Furthermore, cyproheptadine caused significantly more drowsiness than acrivastine (p = 0.021) or placebo (p = 0.013), which did not differ from each other. This study shows that acrivastine is an effective agent in the treatment of cold urticaria and suggests that acrivastine in the dose used lacks adverse effects, such as drowsiness, traditionally associated with antihistamine therapy. PMID- 2901994 TI - Molecular mechanism of beta-adrenergic receptor blockers with intrinsic sympathomimetic activity. AB - beta-Adrenergic receptor (beta AR) blocking agents with intrinsic sympathomimetic activity (ISA) can induce modest increases in beta AR-stimulated activity, such as rate and force of contraction in cardiac tissue. The molecular basis for this activity has been elusive. Previous studies have suggested that these compounds do not stimulate cyclic AMP (cAMP) formation even though activation of adenylate cyclase is the generally accepted mechanism for beta AR promotion of target cell response. In the current studies, we show that several beta AR antagonists with ISA (dichloroisoproterenol, pindolol, and celiprolol) stimulate cAMP accumulation five-, two-, and threefold, respectively, in S49 lymphoma cells, but only if cells are simultaneously incubated with the diterpene forskolin. The KI values observed for inhibition of isoproterenol-stimulated cAMP accumulation or of beta AR [( 125I]iodocyanopindolol) binding for each of the beta blockers with ISA were comparable in magnitude to their respective EC50 values for forskolin-potentiated cAMP accumulation. The forskolin-potentiated responses of these compounds were abolished by the beta AR-antagonist propranolol. These results indicate that the ISA of beta-blocking drugs most likely results from a modest beta AR-mediated stimulation of adenylate cyclase activity. The results further suggest that treatment of target cells with forskolin provides a means to define partial agonism at receptors that are linked to stimulation of adenylate cyclase. PMID- 2901996 TI - Somatostatin as mediator of fat-induced inhibitor of gastric functions. PMID- 2901995 TI - Role of platelet-activating factor in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine and prednisolone. AB - Platelet-activating factor is released from inflammatory cells. It activates neutrophils, releases secondary messengers, and mediates mucosal ulceration and ischemia in the rat. We assessed its possible role in the pathogenesis of ulcerative colitis. Colonic biopsy specimens from patients with active ulcerative colitis and controls were incubated for 4 h in Tyrode's buffer in the presence or absence of 0.2 microM calcium ionophore (A23187) or 50 microliter of antihuman immunoglobulin E. Platelet-activating factor was determined in the tissue by aggregation assay after extraction with 80% ethanol and was confirmed by thin layer chromatography and its inactivation by phospholipases. Platelet-activating factor was not detected in normal mucosa. Only A23187 and antihuman immunoglobulin E stimulated its activity: mean +/- SE, 43.2 +/- 8.6 and 33.0 +/- 6.1 pg/10 mg wet wt, respectively. In active ulcerative colitis basal platelet activating factor activity was 8.9 +/- 3.5 pg/10 mg wet wt. A23187 and antihuman immunoglobulin E induced significantly higher stimulation of platelet-activating factor synthesis when compared with their effects on normal mucosa: 200 +/- 28 and 70 +/- 8.3 pg/10 mg wet wt, respectively. The enhanced stimulation induced by A23187 was dose-dependently inhibited by salazopyrine, 5-amino-salicylic acid, and prednisolone, but not by sulfapyridine. It is thus suggested that platelet activating factor may be involved in the pathogenesis of the inflammatory response in ulcerative colitis and that its inhibition by steroids, 5 aminosalicylic acid, and salazopyrine may be an additional mechanism to explain their therapeutic effects. PMID- 2901997 TI - Total chemical synthesis of a gene for hepatitis B virus core protein and its functional characterization. AB - We have chemically synthesized a DNA duplex of 560 nucleotides that codes for the hepatitis B virus (HBV) core protein. The synthetic gene contains 27 unique internal restriction sites. Thereby, it can easily be mutagenized by replacement of rather short restriction fragments. A number of restriction recognition sequences are in common between the synthetic and the authentic gene, thus allowing for the transfer of synthetic segments into the cloned viral genome. Several unexpected mutations in the synthetic gene were readily corrected utilizing the multiple unique restriction sites. In Escherichia coli, the expression level of the synthetic gene product amounts to about 4% of the total soluble protein. It forms particles closely resembling native HBV cores. After transfer of the synthetic gene into the viral genome, transient expression in a hepatoma cell line yields proteins indistinguishable from the native gene products. The synthetic gene thus provides a useful tool for studies on the structure and function of the isolated HBV core protein as well as the gene and its various products in the viral life-cycle. PMID- 2901999 TI - Insulin and other islet hormones (somatostatin, glucagon and PP) in the neuroendocrine system of some lower vertebrates and that of invertebrates--a minireview. AB - Onto- and phylogenetical studies of the evolution of cells, producing regulatory peptides, belonging to the "hormone families" of insulin, somatostatin, glucagon, and PP (the pancreatic polypeptide), have shown that the islets of Langerhans in vertebrates form a substantial part of the large neuroendocrine system (NES). The NES consists of three major parts, viz. (i) neuronal cells of the central and peripheral nervous systems, (ii) disseminated cells in the mucosa of the alimentary tract (and that of other hollow organs), (iii) the parenchymal cells of the classical endocrine glands. In the NES of coelenterates no evidence of islet hormone production has been obtained, so far. In invertebrates, belonging to the protostomian evolution line, the neuronal parts of the NES predominate markedly, and in the most highly developed phyla, such as artropods and molluscs, clear-cut evidence has been obtained for the presence of cells producing members of the islet hormone families. A "brain-gut axis" for all the four islet hormones is well established in the NES of the pro-craniates, i.e. in the invertebrates of the deuterostomian evolution line. Here, the gut endocrine cells are cells of the disseminated type in the epithelium of the mucosa. A separate islet organ does not occur in the NES until the appearance of the first vertebrates, viz. the Agnatha, some 500 million years ago. Here, a grossly visible islet organ exists, free from exocrine, acinar, pancreatic parenchyma. It is a two-hormone organ with insulin and somatostatin cells only.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2901998 TI - Different alpha 2-adrenoceptor densities in the circular and longitudinal layers of human near-term myometrium as revealed by [3H]-idazoxan binding studies. AB - [3H]-idazoxan, a specific alpha 2-adrenoceptor antagonist radioligand, has been used to characterize alpha 2-adrenoceptors in both circular and longitudinal layers of human near-term myometrium. [3H]-idazoxan binding is reversible, saturable and stereospecific. It labels with high affinity a single population of sites. Competition curves with different alpha 2-adrenoceptor agonists and antagonists show that the binding sites labelled with [3H]-idazoxan have the pharmacological characteristics of alpha 2-adrenoceptors. Though the KD value is similar in both layers (approximately 7 nM), the density of alpha 2-adrenoceptors in the circular layer (324 +/- 21 fmol/mg of protein) is significantly higher than in the longitudinal one (183 +/- 48 fmol/mg of protein). PMID- 2902001 TI - A new RFLP with StuI and probe cX55.7 (DXS105) and its usefulness in carrier analysis of fragile X syndrome. AB - The authors report on a new RFLP at DXS105 suitable for carrier detection of fragile X syndrome. PMID- 2902000 TI - Genetic mapping of anhidrotic ectodermal dysplasia: DXS159, a closely linked proximal marker. AB - Three families with anhidrotic ectodermal dysplasia (AED) have been studied by linkage analysis with seven polymorphic DNA markers from the Xp11-q21 region. Previously reported linkage to DXYS1 (Xq13-q21) has been confirmed (z (theta) = 4.08 at theta = 0.05) and we have also established linkage to another polymorphic locus, DXS159, located in Xq11-q12 (z (theta) = 4.28 at theta = 0.05). Physical mapping places DSX159 proximal to the Xq12 breakpoint of an X autosome translocation found in a female with clinical signs of ectodermal dysplasia. Of all markers that have been used in linkage analysis of AED, DXS159 would appear the closest on the proximal side of the disease locus. PMID- 2902002 TI - Involvement of neurohumoral transmitters in electroshock induced hyperthermia in mice. PMID- 2902003 TI - Allergic contact dermatitis to nickel is associated with a Taq I HLA-DQA allelic restriction fragment. AB - RFLP analysis of the HLA class II genes DRA, DQA, and DQB was performed in 33 patients with allergic contact eczema to nickel. A significant association with a Taq I HLA-DQA allelic restriction fragment was found. Twenty-two of 33 patients compared to 31 of 100 healthy controls had a 4.5-kb DQA fragment (corrected P value less than 0.05, relative risk 4.5, and etiologic fraction 0.52). In order to study whether the magnitude of the response in a lymphocyte proliferative assay to nickel sulfate was controlled by HLA class II genes or not, the patients were divided into low, intermediate, and high responders. No significant differences were found in the distribution of Taq I HLA class II allelic patterns between the groups. PMID- 2902005 TI - Alterations in circulating neurotransmitters & cortisol with severity of breast cancer. PMID- 2902004 TI - Genotyping chickens for the B-G subregion of the major histocompatibility complex using restriction fragment length polymorphisms. AB - Chicken B-G-subregion cDNA probes were used to analyze restriction fragment length polymorphisms (RFLP) of the B-G subregion of the chicken major histocompatibility complex. Genomic DNA from chickens representing 17 of the 27 standard B haplotypes were digested with restriction endonucleases and analyzed in Southern hybridizations with two cDNA clones from the B-G subregion. Each B-G genotype was found to produce a unique pattern of restriction fragments in these Southern hybridizations. With 15 of the 17 genotypes examined, the different genotypes could be readily distinguished in hybridizations produced with DNA digested with a single restriction enzyme, PVU II. The two additional genotypes produced nearly identical patterns in PVU II preparations and with three additional enzymes as well, but were readily distinguishable in Eco RI digestions. For many of the haplotypes, samples from several individuals in different flocks were examined. In every instance, genotyping by RFLP pattern was found to confirm the B-G allele assigned serologically. PMID- 2902006 TI - In defense of traditional antihypertensive therapy. PMID- 2902007 TI - In defense of alternative antihypertensive therapy. PMID- 2902008 TI - Adrenal and vascular tyrosine hydroxylase activity in Goldblatt hypertension. AB - To examine the role of the sympathetic nervous system in hypertension, the in vitro activity of tyrosine hydroxylase was examined in one-kidney, one clip (1K1C) and two-kidney, one clip (2K1C) hypertensive rabbits and their respective controls 2 weeks after surgical procedures. The in vitro activity of tyrosine hydroxylase provides a measure of catecholamine synthesis and serves as a biochemical index of activity of noradrenergic neurons and the adrenal medulla. Mean atrial pressure rose from 91.5 +/- 1.0 to 128.5 +/- 5.6 mm Hg (p less than 0.01) in the 1K1C group and from 91.8 +/- 1.3 to 106.5 +/- 5.0 mm Hg (p less than 0.02) in the 2K1C group, whereas no change in blood pressure was found in their respective controls. Adrenal tyrosine hydroxylase activity was increased 85% in the 1K1C group, as compared with values in one-kidney controls (from 11.8 +/- 1.5 to 21.8 +/- 1.1 pmol CO2/min/mg; p less than 0.0002), and was increased 49% in the 2K1C group, as compared with values in two-kidney controls (from 8.01 +/- 1.2 to 11.9 +/- 1.1 pmol CO2/min/mg; p less than 0.02). In the 1K1C group, proximal mesenteric tyrosine hydroxylase activity was decreased 46% compared with values in one-kidney controls (from 23.5 +/- 5.0 to 12.8 +/- 2.5 pmol CO2/min/mg; p less than 0.03) and distal mesenteric tyrosine hydroxylase activity was decreased 42% (from 7.73 +/- 1.2 to 4.46 +/- 0.8 pmol CO2/min/mg; p less than 0.03). In the 2K1C group, neither proximal nor distal mesenteric tyrosine hydroxylase activity was altered. Tyrosine hydroxylase activity was not detectable in the femoral arteries, or in the thoracic and abdominal aorta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902009 TI - Characterization of the Vibrio cholerae ToxR regulon: identification of novel genes involved in intestinal colonization. AB - A gene fusion library of Vibrio cholerae classical strain O395 was generated by using a broad host range vector for delivery of the transposon TnphoA. The insertion library was screened for colonies expressing alkaline phosphatase positive (PhoA+) fusion proteins on LB agar at 30 degrees C in the presence of 0.2% glucose. Over 600 PhoA+ strains were isolated and then tested for regulation of their gene fusions in broth media that permitted high or low expression of cholera toxin. This strategy resulted in the isolation of 60 TnphoA (Tn5 IS50L::phoA) fusions to genes encoding secreted proteins that are apparently coordinately regulated with cholera toxin. Introduction of a toxR null mutation into 10 of these fusion strains confirmed that these TnphoA gene fusions are controlled either directly or indirectly by the cholera toxin transcriptional activator encoded by toxR. A combination of Southern and immunoblot analysis identified 17 distinct ToxR-regulated genes in V. cholerae O395. Many of these insertions were located in one of the two cholera toxin operon copies of strain O395, as well as a large gene cluster involved in the biogenesis of the toxin coregulated pilus colonization factor. In addition, insertions were identified in genes that had no effect on either cholera toxin or toxin-coregulated pilus expression. Several of these insertions were localized to a cluster of four genes, the disruption of any of which by TnphoA reduced the ability of strain O395 to colonize the intestines of suckling mice. The product encoded by this second gene cluster was named accessory colonization factor to describe its possible role in cholera pathogenesis. These studies reinforce the contribution of ToxR-regulated genes to the virulence properties of V. cholerae. This report also demonstrates a new approach for the identification of bacterial virulence factors, based on the characterization of genes that are regulated by the same environmental signals that control the expression of a known virulence factor. PMID- 2902010 TI - Cloning and characterization of a new type of fimbria (S/F1C-related fimbria) expressed by an Escherichia coli O75:K1:H7 blood culture isolate. AB - The Escherichia coli blood culture isolate BK658 (O75:K1:H7) expresses F1A and F1B fimbriae as well as a third fimbrial type which reacts with anti-S-fimbrial antiserum but fails to show S-specific binding properties (i.e., agglutination of bovine erythrocytes). To characterize these fimbriae, we cloned the respective genetic determinant in E. coli K-12. The resulting recombinant clone HB101(pMMP658-6) expresses fimbriae of 1.2-micron length and a diameter of approximately 7 nm. The determinant codes for the fimbrillin subunit, a protein of 17 kilodaltons in size, and for at least five other proteins of 87, 31, 23, 14.3, and 13.8 kilodaltons. By restriction analysis and by DNA-DNA hybridization, it could be shown that the cloned fimbrial determinant of strain BK658 exhibits a high degree of sequence homology to the gene clusters coding for S fimbrial adhesins (sfa) and F1C fimbriae (foc). By using the Western blot (immunoblot) technique and a quantitative enzyme-linked immunosorbent assay, it could be further demonstrated that the cloned fimbriae of BK658, S fimbriae, and F1C fimbriae share cross-reactive epitopes as well as antigenic determinants specific for each fimbrial type. No antigenic cross-reactivity with F1C fimbriae could be detected. The results indicate a genetical and serological relatedness of the cloned fimbriae to S fimbriae and F1C fimbriae. Therefore, this new type of fimbriae is preliminarily termed S/F1C-related fimbriae (Sfr). PMID- 2902011 TI - Isolation and characterization of the localized adherence factor of enteropathogenic Escherichia coli. AB - The binding factor of enteropathogenic Escherichia coli O111:H- responsible for localized adherence (LA) on HeLa cells was investigated. Inhibition of LA by carbohydrates and lectins showed that the reactive epitope on HeLa cells contains N-acetylgalactosamine units. Treatment of bacteria with EDTA for extraction of lipopolysaccharides eliminated these polymers as binding factors. Such treatment also caused a marked increase in adhesion suggesting steric hindrance by lipopolysaccharides of the LA factor binding capacity. Immunoblotting with rabbit antibodies showed a strong reaction with two components with approximate molecular sizes of 29 and 32 kilodaltons (kDa) present in the outer membrane preparations of bacteria. Both the absorbed rabbit immune serum and the outer membrane preparation of the bacteria inhibited bacterial adhesion by 100%. Outer membrane components were isolated from an N-acetylgalactosamine-agarose column by elution with KSCN, labeled with 125I, and immunoprecipitated with absorbed rabbit hyperimmune antiserum. The only component precipitated was the protein doublet at 29 to 32 kDa corresponding to the components detected by immunoblotting. The predominant component was always the 32-kDa polypeptide. We conclude that this component of the outer membrane is the best candidate for the LA factor in enteropathogenic E. coli. PMID- 2902012 TI - Mutants of Actinomyces viscosus T14V lacking type 1, type 2, or both types of fimbriae. AB - Mutants of Actinomyces viscosus T14V lacking type 1 or type 2 fimbriae or both were selected by their failure to react with rabbit antibodies against either or both fimbrial antigens. Immunospecific double labeling with iron dextran and ferritin-conjugated antibodies showed two types of fimbriae on individual cells of the parent organism, a single type on mutant strains with type 1+2- and type 1 2+ fimbriae and no labeled or unlabeled fimbriae on a type 1-2- fimbria-deficient strain. The mutational loss of one fimbrial antigen did not appear to affect expression of the other, since bacteria with one or two types of fimbriae bound similar amounts of a monoclonal antibody directed against the fimbrial antigen present on both bacterial phenotypes. The strong adsorption of strains with type 1+2+ or 1+2- fimbriae to saliva-treated hydroxyapatite and weak adsorption of those with type 1-2+ or no fimbriae was consistent with the known involvement of type 1 fimbriae in this attachment process. Similarly, the A. viscosus lectin was clearly associated with the expression of type 2 fimbriae, since only the strains with type 1+2+ or 1-2+ fimbriae participated in lactose-sensitive coaggregations with Streptococcus sanguis 34. Further studies using the fimbria-deficient mutant strains showed that aggregation of A. viscosus T14V in the presence of sialidase treated human saliva involved both types of fimbriae, whereas neither type was required for the lactose-resistant coaggregation of the organism with certain streptococcal strains. PMID- 2902014 TI - Evidence that in vitro adherence of Klebsiella pneumoniae to ciliated hamster tracheal cells is mediated by type 1 fimbriae. AB - Clinical isolates of fimbriated and nonfimbriated Klebsiella pneumoniae were examined for the ability to adhere to hamster tracheal cells cultured in vitro. Fimbriated-phase K. pneumoniae adhered preferentially to ciliated cells, whereas nonfimbriated-phase organisms were not adherent. The adherence was inhibited by D mannose but not D-glucose, suggesting that type 1 fimbriae serve as the adhesin in the attachment process. PMID- 2902013 TI - Adsorbed salivary proline-rich protein 1 and statherin: receptors for type 1 fimbriae of Actinomyces viscosus T14V-J1 on apatitic surfaces. AB - Use of specific fimbria-defective mutants derived from Actinomyces viscosus T14 has shown that salivary acidic proline-rich protein 1 and statherin serve as receptors for type 1 fimbriae which mediate attachment of the organism to experimental pellicles on apatitic surfaces. PMID- 2902015 TI - Inhibition of growth and differentiation of fetal hamster gonads grafted into the adult testis. AB - A cytomorphological analysis of the effect of adult testes on growth and differentiation of grafted fetal testis or ovaries was performed in hamsters. Fetal gonads, taken at 14 days post-coital age, were grafted for 30 days either under the renal capsule or testicular capsule of scrotal or cryptorchid testes of adult hamsters (weight 115 +/- 23 g). Renal grafts were also performed in males castrated 30 days prior to receiving the fetal gonads. Growth and differentiation of the fetal gonads (testis or ovary) was totally inhibited by the scrotal testis. When the cryptorchid testis was the recipient of fetal gonads, inhibition was correlated inversely with the degree of spermatogenic damage elicited in the cryptorchid testis. No inhibition was observed in fetal gonads grafted under the kidney capsule, nor in castrated, normal or cryptorchid animals. As normal growth and differentiation of both testis and ovary occurred when grafted under the kidney capsule, the inhibitory effect of adult gonads seems to be unrelated to plasma testosterone levels in the host, as levels were undetectable in castrated hamsters and reduced drastically in cryptorchid animals. At the same time, the testicular-inhibiting substance in normal animals did not act at a distance, since its effect was restricted to fetal gonads grafted under the testicular capsule. This inhibitory substance may correspond to the spermatogonial chalone, known to be produced by differentiating spermatogenic cells (mainly spermatocytes and round spermatids in the rat and mouse); these chalones prevent spermatogonial proliferation and, consequently, the critical number of spermatogonia needed to enter meiosis is not attained. It is doubtful if the same substance has the ability to differentiate the fetal ovary or if this effect can be ascribed to a more complex situation involving other testicular peptides of paracrine action and/or locally high levels of androgens. PMID- 2902016 TI - Carcinoid tumour cells in long-term culture: release of serotonin but not of tachykinins on stimulation with adrenoceptor agonists. AB - Tumour cells from a lymph-node metastasis of a midgut carcinoid tumour, immunoreactive for serotonin and substance P, were isolated and kept in culture for 2 months. The formation of large clusters or islets of tumour cells was paralleled by an increase in immunoreactive tachykinins (neuropeptide K and substance P) in the culture medium. The concentration of tachykinins declined subsequently despite good viability of the cells. Spontaneous release of serotonin into the culture medium was much greater than that of tachykinins, and remained stable throughout the study. These findings indicate different turnover rates and/or different storage sites for the peptides and the amine. In stimulation experiments, a dose-dependent release of serotonin, but not of tachykinins, was induced by a beta-adrenoceptor agonist (isoprenaline), while stimulation of alpha-adrenoceptors (noradrenaline) was not effective in releasing any of the substances. Pretreatment of the cultures with a beta-adrenoceptor antagonist (propranolol) or stimulations after calcium deprivation did not influence the isoprenaline-induced release of serotonin. These findings may indicate a modification of genuine beta-adrenoceptors during culture. PMID- 2902017 TI - A Taqi RFLP of the human TGF alpha gene is significantly associated with cutaneous malignant melanoma. AB - A TaqI restriction fragment length polymorphism (RFLP) of the human transforming growth factor alpha (hTGF alpha) locus was analyzed in DNA from 63 normal individuals, 34 malignant melanoma (MM) cell lines, and 18 melanoma biopsy specimens. The frequency of a 2.7-kb allele (0.18) in MM cell lines was significantly higher (p less than 0.01) than in lymphoblastoid cell lines (LCLs) derived from unaffected controls (0.05). The frequency (0.14) in MM biopsies was similar to that in MM cell lines although, owing to the small numbers investigated, it was not significantly higher than in controls. In the case of 5 MM patients who were constitutionally heterozygous for alleles at the TGF alpha locus, no apparent losses of heterozygosity were observed in the corresponding tumour DNA. Thus, the constitutional presence of the 2.7-kb allele may be a risk factor for melanoma. PMID- 2902019 TI - Fourth Congress of the IFFLP. Symposium proceedings. Ottawa, Canada, June 1986. PMID- 2902018 TI - A new immunotoxin built by linking a hemolytic toxin to a monoclonal antibody specific for immature T lymphocytes. AB - Hybrid molecules built by conjugation between monoclonal antibodies (MAbs) and toxins are currently being experimentally tested as potential new anti-cancer agents. These immunotoxins have mainly used the plant toxin ricin as the toxic component, which inhibits protein synthesis at the ribosome level. We present an alternative for toxic components using a hemolytic toxin acting at the membrane level, due to its phospholipase activity. The hemolytic toxin (HT), isolated from the sea anemone Stoichactis helianthus, has been conjugated to an antibody towards an antigen expressed on immature T lymphocytes (IOR-T6), by means of an artificial disulphide bridge. The hybrid IOR-T6-HT exhibits no hemolytic activity unless it is reduced. It is toxic for cells (CEM) expressing the IOR-T6 antigen and non-toxic for cells (K562) not bearing the antigen. An excess of unconjugated antibody reverses the toxicity. Immunotoxins based on membrane-active, hemolytic toxins can be a useful alternative when directed towards antigens which do not mediate internalization, as is the case for most carcinoma antigens. PMID- 2902020 TI - Self-palpation to assess cervical changes in relation to mucus and temperature. AB - Women experienced in cervical self-palpation recognize fertile characteristics when the cervix is high, open, soft, and straight; this happens under estrogenic influence. The cervix is said to show infertile signs when it is low, closed, firm, and lying against the vaginal wall; that change occurs quickly under progesterone influence. The objective of this study was to assess the time relationship among changes in the cervix observed by self-palpation, changes in cervical mucus as observed by women, and the shift in basal body temperature during ordinary cycles. A total of 215 symptothermal charts from natural family planning users were analyzed. The duration of the change from the maximum fertility characteristics to the postovulatory return to definite signs of infertility was measured. This duration ranged from 1 to 7 days, with a mean of 2.65. The timing of maximum fertility signs in the mucus was compared with that of maximum fertility signs in the cervix: it varied from 3 days before to 6 days after, with a mean of 0.48 day. The timing of the first high temperature was compared with that of return to definitely infertile characteristics: it varied from 6 days before to 3 days after, with a mean of -0.69 day. Some of the variation may be due to the presence of inexperienced users in the sample. However, a mean difference of half a day between the most fertile cervix and the most fertile mucus on one hand and between the first day of infertile cervix and the first high temperature on the other hand suggest that the cervical changes could be useful indicators of estrogen and progesterone actions. PMID- 2902021 TI - Detection of the fertile phase from changes in cervico-vaginal fluid volume. AB - Characteristic changes in cervico-vaginal fluid (CVF) volume which occur during the menstrual cycle might be used to detect the fertile phase. Twenty-five normal women were asked to withdraw CVF and measure its volume at home using a small, disposable, graduated vaginal aspirator. In 16 cycles day 0 (ovulation) was defined as the day of maximum follicular diameter according to serial ultrasound examination. A rise in CVF volume occurred between day -9 and -2 and a peak between day -4 and 0. In these sixteen, and in a further 72 cycles, day 0 (time of maximum fertility) was taken as the day of peak cervical mucus secretion. CVF volume rose, on the average, on day -6.2 (range -17 to -2) and peaked on day -0.8 (range -5 to +2). In two cycles, no rise and peak were identified. Changes in CVF volume were easy to recognise and could be useful to couples wishing to achieve pregnancy. PMID- 2902022 TI - Breast-feeding and natural family planning. AB - The records of 50 Australian postpartum women who intended to breast-feed for longer than 6 months were analyzed. Fifty percent of the women breast-fed longer than 12 months, and 50% resumed menses by 40 weeks after childbirth. Fifty-four women provided records of mucus and BBT for at least 4 weeks before resumption of menses. Ovulation before menses while fully breast-feeding was probable in only one woman. Fifty percent of the first postpartum cycles had a short luteal phase. Thirty-two women chose NEP to avoid pregnancy during the study period. Mucus and BBT proved to be a good marker of ovulation during postpartum cycles. The mean number of days available for intercourse according to the Ovulation Method was 22.6 days between 6 and 12 postpartum weeks, and 12 days during the 4 weeks before menses. Confidence in NFP during lactational amenorrhoea and first postpartum cycles is analyzed. Finally, research aimed at improving the teaching and use of NFP for postpartum breast-feeding women is described. PMID- 2902023 TI - Hormonal background of lactational infertility. PMID- 2902024 TI - Breast-feeding patterns and lactational amenorrhoea among the Warli tribals: a socioanthropological inquiry. AB - Data on breast-feeding patterns and lactational amenorrhoea were collected as part of a socioanthropological inquiry conducted among the Warli tribals living along the west coast of India. A need to study and length of lactational amenorrhoea among these tribal women arose because in the complete absence of the use of contraception, lactational amenorrhoea acts as a natural birth spacer in this population. Analysis of the data shows that the suckling frequency during lactation, the sex of the child born, and the nutritional status of the women influence the length of lactational amenorrhoea. The consequences of variations in the length of lactational amenorrhoea on other related demographic parameters are also mentioned. PMID- 2902025 TI - Natural family planning and pregnancy outcome. AB - A prospective study with 664 married couples using a particular symptothermal method of natural family planning (NFP) offered the opportunity to investigate the relationship between NFP and the alleged risk of an increased incidence of spontaneous abortions and malformations. An analysis of 611 pregnancies with known outcome did not confirm such a risk. On the contrary, there was a trend toward fewer spontaneous abortions and malformations in our clients. This might be due to special care given to the beginning pregnancy as soon as it became evident. PMID- 2902026 TI - Analysis of the outcome of 124 pregnancies produced during NFP. AB - The outcome of 124 pregnancies produced during the use of CM (Billings) of NFP is analyzed. The spontaneous abortion rate was 8%. The women who became pregnant in the less fertile period (+/- 3 days from peak day) presented a higher rate of spontaneous abortions (13.9%) than the women who became pregnant during the most fertile period (peak day +/- 2 days), who presented a 4.3% spontaneous abortion rate. Among the 115 living infants (one twin pregnancy) there was one congenital malformation (0.8%), a cleft palate. The sex ratio of the infants was 0.59 (48 females and 67 males), which is not significantly different from the 0.51 sex ratio expected. When conception occurred during the most fertile period, the sex ratio was 0.37, in contrast to the sex ratio of 0.76 when conception occurred in the less fertile period; this is a highly significant difference (P less than 01). PMID- 2902027 TI - Natural methods for fertility control: a prospective study--First Part. AB - This study describes 4 years of verification of effectiveness and applicability of BBT and symptothermal methods. The couples chosen had to undergo a 6-month long study phase, and be psychologically motivated and well trained in NFP. During this period, particular emphasis was given to the motivational factor, which was expanded in its anthropological, relational, pedagogical and, sometimes, moral contents. Four hundred and sixty couples entered the program, for a total of 8,140 cycles, in which BBT, cervical mucus, and intercourse were charted. The Pearl Index for unplanted pregnancies was 3.6. Twenty-five unplanned pregnancies occurred in couples using NFP for spacing, and no pregnancies were reported in limiters. PMID- 2902029 TI - The natural family planning programme in Bangladesh. AB - A 12-month evaluation of the Ovulation Method of Natural Family Planning programme in Bangladesh is presented. Four hundred and forty-eight women entered the programme, 232 for spacing, 184 for limiting, and 32 to achieve pregnancy. Of the participating couples, 79% lived in rural areas and 20.3% were illiterate. The 416 who learned the ovulation method for avoiding pregnancy completed 2,358 months of use, with 14 unplanned pregnancies during the study period, which represents a pregnancy rate of 7.2 according to the Pearl Index. The discontinuation rate in the 12-month period was 2.4%. PMID- 2902028 TI - The development of fertility assay kits: an overview. AB - This paper analyzes the importance of developing fertility assays kits, specially in order to shorten the estimate of the fertile period in NFP users. It presents the criteria that an assay kit needs to meet. Urinary hormones, metabolites of progesterone, estrogens, and luteinizing hormones are analyzed as fertile-period markers. Progesterone and estradiol in saliva, as well as other constituents of saliva, the volumetric vaginal aspirator, and the change in the electrical conductivity of the vaginal fluid are also analyzed with the same purposes. PMID- 2902030 TI - Demographic study on the family planning behaviour of the German population: the importance of natural methods. AB - A total of 1,267 women in the F.R.G., aged from 15 to 45 years, were interviewed about their family planning behavior and the importance of natural methods of family planning (NFP) in a representative demographic study. It was found that 19.6% of the respondents were not sexually active. The others used various methods, as follows: pill, 38.4%; IUD, 10.3%; condom, 5.9%; diaphragm, 2.1%; spermicides, 0.8%; withdrawal, 3.4%; NFP methods, 3.9%. The main reason for rejecting a method was a possible medical risk. Of the responding women, 73% had some previous knowledge about NFP; 47% of them found such methods to be interesting, and approximately 20% indicated a high probability of the use of NFP methods in the future. PMID- 2902031 TI - Factors affecting client satisfaction in the instruction and usage of natural methods. AB - A cross-sectional sample of women who had attended "at least one" instruction is utilized to assess dimensions of client satisfaction with instruction in and usage of natural family planning (NFP) methods (N = 440). Ovulation and symptothermal methods are represented by five autonomous programs in the state of Oregon. Psychosocial factors affecting experiences with natural methods are assessed using a mailed questionnaire yielding a 57% response rate and follow-up interviews with 28 couples from the initial sample. Findings yield an overall "effectiveness" rate of 94% for family-size limiters, and 88% for spacers. There was no difference in overall marital happiness between NFP users and discontinuers, although this may be more related to the overall high level of marital happiness for the total sample compared with the general population. Couples describe their perceptions of the effects of natural methods on marriage, communication patterns, sexual satisfaction, and family life. Implications for program development and research are explored. PMID- 2902032 TI - Psychological aspects of NFP practice. AB - A psychological investigation was implemented to find out if NFP users are characterized by special personality traits and if there are any correlations between NFP practice and changes within the marriage partnership. A total of 258 NFP users, both women and men, were investigated with questionnaires of the type generally used in the field of personality research in the Federal Republic of Germany, and also with questionnaires concerning the partnership and attitudes toward pregnancy, sexuality, and childbirth. It was found that with respect to personality traits, the NFP user does not differ considerably from people designated as "normal population." Only their attitudes toward sexuality are more positive and uninhibited, and the women feel less subjectively helpless than the standard sample. Furthermore, there is a connection between increased NFP experience and changes within the partnership, in that there is a reduction of "dominant" attitude (in both men and women) with growing NFP experience. Couples with long NFP experience and NFP beginners have nearly the same degree of well being between the partners, whereas couples who have just passed the learning phase show more ill-feeling between husband and wife. Factors concerning the partnership account much more for the differences in marital satisfaction than do sociodemographic variables or personality traits. PMID- 2902033 TI - Analysis of a representative sample of natural family planning users in England and Wales, 1984-1985. PMID- 2902034 TI - Acceptability of the modified mucus method: study of the psychosocial factors affecting acceptance. AB - A three-phase study designed to study the acceptability and use-effectiveness of the modified mucus method covered a sample of 2,601 poor rural migrant women living in eight low-income areas--villages and resettlement slum colonies. In phase I, the women were exposed to NFP awareness, i.e., the modified mucus method, and 61.6% of the women accepted the method, and agreed to learn and use it. The learning phase is three cycles. Of these acceptors, 83.7% were fertile. A large percentage of the acceptors are Hindus. The low acceptance by the Sikhs was who were non pregnant, menstruating cohabiting. 15.3% were nonmenstruating owing to pregnancy or breast feeding; 0.9% were menstruating, but not cohabitating; 35.4% of the women were not interested in learning or using the method. A comparative study of the acceptance and nonacceptance for the selected sociodemographic and family planning variables is analysed. The acceptors of NFP differed significantly from the acceptors of sterilization and IUD in their occupation, educational levels, duration of marriage, number of living children, number of living sons, knowledge of family planning, and previous use of family planning. PMID- 2902035 TI - Varicocelectomy: twenty-five years of experience. AB - The effectiveness of varicocelectomy in the therapy of male infertility has been well documented. We favor a modification of the Ivanissevich procedure. It is simple and can be done well by the average surgeon, and results have been excellent. Surgery is indicated by poor sperm motility and immaturity. The presence of a varicocele with the absence of this combination of semen defects would not be sufficient indication for surgery. The actual effects of varicocele on fertility are still unknown, for many men with varicocele have normal semen qualities and adequate fertility. The study of our varicocelectomy failures does not reveal any preoperative differences between them and those that show improvement after surgery. PMID- 2902036 TI - Second-look laparoscopy in the treatment of endometriosis. AB - The results of second-look laparoscopy were compared with subjective symptomatology and findings at pelvic exploration in 36 patients who had received conservative treatment for endometriosis. In the 14 patients given pharmacologic treatment, second-look laparoscopy demonstrated active endometriosis in 57.1%, whereas pelvic pain was present in 64.3% and gynecologic examination was positive in 28.6%. In the 22 patients who underwent surgery, active endometriosis was detected by second-look laparoscopy in 31.8%, whereas 40.9% reported pelvic pain and pelvic examination was positive in 31.8%. Thus clinical signs and symptoms were unreliable in the diagnosis of endometriosis recurrence, whereas laparoscopy was indispensable. It should be programmed for 6 months from the end of medical treatment and 12 months after surgery; however, if the pain symptomatology recurs, then laparoscopy is performed immediately. PMID- 2902037 TI - Incidence of spontaneous abortion following artificial insemination by donor. AB - This study examines the frequency of spontaneous abortions in pregnancies achieved by artificial inseminations with donor semen (AID), with special respect to the use of cryopreserved semen and ovulation induction with clomiphene citrate. The abortion rate was found to be similar in AID series using frozen semen to those using fresh semen, nor was the rate increased in composite AID series (both fresh and frozen semen) when compared with the rate of spontaneous abortions in the general population. When clomiphene was used, the abortion rate was increased only in groups of anovulatory and irregularly ovulating women. Those AID series where all women treated are given clomiphene show no increase in abortion rates. The discussion is focused on factors that influence the abortion rate and on possible etiological factors. PMID- 2902038 TI - Infertility: a preventable epidemic? AB - Infertility with a broad etiological background has only been treated, but not prevented. With the exception of ovulation induction, the success rate of pregnancy in most cases has been rather dismal in view of the high socioeconomic burden. A questionnaire survey of the cost of infertility investigation and treatment has been undertaken, and it has been estimated that the cost of infertility due to the sequelae of sexually transmitted diseases ranges in the vicinity of $64 billion, which is to be compared with the prevention cost of $335,000. Recommendations on preventative aspects are discussed. PMID- 2902039 TI - Ovulation-inducing drugs versus progesterone therapy for infertility in patients with luteal phase defects. AB - The efficacy of ovulation-inducing drugs (OVI) for treating infertility related to luteal phase defects (LPD) was compared with the efficacy of progesterone vaginal suppositories (PVS). Patients were divided into two groups: (1) LPD secondary to immature follicles and (2) pure LPD, in which the follicle was mature. Twenty-four of 31 women (77%) with pure LPD conceived (one aborted) during the first 6 months, compared with only 3 of 27 (11%) treated with OVI--and 2 of 3 aborted. However, in women with LPD secondary to immature follicles, 14 of 20 (70%) treated with OVI and PVS conceived (and one aborted) compared with 7 of 10 conceiving (70%) with OVI only (four aborted), and 3 of 12 conceived (25%) with PVS only (none aborted). Thus, both PVS and OVI are effective in treating LPD; follicular maturation studies help determine the proper choice. PVS appears to decrease the risk of abortion in both categories. PMID- 2902040 TI - Persisting ectopic pregnancy after segmental resection. PMID- 2902041 TI - Ovarian stimulation during gonadotropin treatment after hCG administration monitored by ultrasound and serum estradiol and progesterone. AB - Ovarian volumes, measured with ultrasound, and serum estradiol and progesterone concentrations were studied during gonadotropin treatment cycles 1 week after hCG administration in 23 patients, of whom nine had polycystic ovarian syndrome (PCO), eight oligomenorrhea or amenorrhea corresponding to WHO group II (OMG), and six hypogonadotropic amenorrhea corresponding to WHO group I (HGT). The ovarian volumes were greater in the PCO and HGT groups than in the OMG group. The serum estradiol and progesterone concentrations correlated more closely with ovarian volumes in the HGT group than in the PCO and OMG groups. The present study failed to demonstrate a lower risk of hyperstimulation in the HGT group in comparison with the PCO and OMG groups. Six patients conceived, and ovarian volumes were greater and serum progesterone concentrations higher during conceptual cycles than during nonconceptual cycles. PMID- 2902042 TI - Scanning electron microscopic study on the shape of infertile seminiferous tubules: a hypothesis of pathogenesis of idiopathic male infertility. AB - The shape of infertile seminiferous tubules was studied on testicular biopsied specimens from patients with idiopathic male infertility using the scanning electron microscope. A parallel study of the same sections was performed by ordinary light microscopy. Normal seminiferous tubules were revealed to be shaped like a weaving cylinder, whereas infertile seminiferous tubules were strangulated in various places, or appeared similar to a tail-like rope which became gradually more slender. These strangulated or slender parts of tubules seemed to correspond to the smaller tubules with thickened tubular walls that were recognized under the light microscope. It is suggested that these thickened tubular walls suppress spermatogenesis by a nutritional disturbance, and the strangulations of infertile tubules interfere with sperm transport by tubular blockage or germinal disorganization and interrupted contractions of the tubules. PMID- 2902043 TI - Immunosuppressive activity of human amniotic fluid of normal and abnormal pregnancies. AB - Twenty specimens of amniotic fluid (AF) obtained between week 16 and 18 of gestation from normal pregnant women and six specimens from pregnant women in which trisomia of chromosome 21 was found were tested for immunosuppressive activity. Incubation of normal human donor lymphocytes with 0.2-1 mL of AF from normal pregnant women for one hour at 37 degrees C was sufficient for induction of significant inhibition of the ability of these cells to induce a local xenogeneic graft-versus-host reaction (GVHR) as well as inhibition of E and E active rosette formation, the GVHR being the most sensitive test. On the other hand, amniotic fluid obtained from the six pregnant women in which trisomia of chromosome 21 was found showed no inhibitory activity in either the E or E-active rosette formation, nor in the local xenogeneic graft-versus-host reaction. AF from all the women tested was found to have no effect on phenotype expression of the lymphocytes, as tested by the monoclonal antibodies OKT4+ and OKT8+, nor on B lymphocytes, as tested by surface immunoglobulins. No correlation was found between the alpha-fetoprotein levels in the sera of those women and the immunosuppressive activity. These findings indicate that genetic defects of the conceptus are not limited to the embryo but may affect the composition of immunosuppressive components present in normal amniotic fluid. PMID- 2902045 TI - Glutamic-oxaloacetic transaminase isozymes in human seminal plasma and sperm extracts. AB - Leakage of glutamic-oxaloacetic transaminase (GOT) can be used as an indicator of cryo-damage for mammalian spermatozoa. However, two GOT isozymes exist: mitochondrial (m-GOT) and cytosolic or soluble (s-GOT), with acid and alkaline pH optima, respectively. The levels of these GOT isozymes were determined in samples of cell-free human seminal plasma and sperm extracts over a pH range of 3.8 to 9.6. Optimum GOT activities were found at pH 5.2 using cacodylate-HCl buffer (m GOT) and pH 8.4 using barbital buffer (s-GOT). Differential inhibition studies with adipate (which inhibits s-GOT) were misleading because of the presence of another NADH-linked enzyme able to use adipate as a substrate. Only relatively low levels of m-GOT could be extracted from human spermatozoa (21.4 +/- 31.5 [SD] mU/10(8) cells vs. 202.3 +/- 49.4 mU/mL seminal plasma; n = 20). Consequently, future studies on GOT leakage should be carried out at the alkaline pH optimum, and will therefore measure s-GOT, making this a marker for plasma membrane integrity rather than a measure of mitochondrial damage. PMID- 2902044 TI - Endocrine status and growth after malignancy treated in childhood or adolescence. AB - Six girls and three boys, asymptomatic after treatment for acute lymphoblastic leukemia (ALL) or endodermal sinus tumor (EST), were investigated for endocrine status and growth. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), prolactin (PRL), testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), testosterone binding capacity (TeBC), 17 alpha-hydroxyprogesterone (17-OHP), progesterone (P), thyroxine (T4), thyroid stimulating hormone (TSH), and cortisol were measured, and pubertal stage and bone age were determined. Growth was evaluated according to accepted curves for height and weight. Four of the girls had normal pubertal development, with serum FSH, LH, and E2 levels correlating to the phase of the menstrual cycle. Only one of the girls had ovulatory cycles (increase in P level). The girl treated for EST by abdominal irradiation had gonadal failure, with postmenopausal serum levels of FSH, LH, and E2. Her karyotype was normal. One of the girls was still prepubertal. None of them was hyperandrogenemic. One boy who was treated with bone marrow transplantation and total body irradiation had gonadal failure. One boy was still prepubertal, and the third boy showed normal pubertal maturation and normal serum FSH, LH, and T levels. All the patients except the boy treated with bone marrow transplantation and irradiation were normoprolactinemic; in addition, all had normal thyroid and adrenal function. Height and weight curves were normal in seven of the patients after the cancer therapy. The girl with EST had finished her growth before the irradiation therapy began. The boy treated with bone marrow transplantation and irradiation failed to exhibit further growth after beginning leukemia therapy at the age of 9.3 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902046 TI - Changes in the aging brain as they affect psychotropics: a review. AB - This article reviews a number of neuroanatomic and neurochemical changes that occur in the brain with aging, and focuses specifically on those that may affect the response to psychotropic drugs. We hope to increase physicians' awareness of these "central," or brain, changes, that occur with aging when prescribing and monitoring psychotropic use, since the traditional emphasis in prescribing for the elderly has rested with the review of pharmacokinetic, or "peripheral" organ changes. PMID- 2902048 TI - Adequate analgesia. PMID- 2902047 TI - Central noradrenergic neurons and vascular non-collagen protein in the initial phase of two-kidney, one-clip renovascular hypertension. AB - Rats had been given intraventricular injection of 6-hydroxydopamine (6-OHDA) before clipping the unilateral renal artery (2K-1C) that caused selective ablation of the central noradrenergic neurons. Central catecholamines and the in vivo incorporation of 3H-proline into vascular non-collagen protein were determined in 2K-1C rats in the acute hypertensive stage. It is suggested that increased non-collagen protein synthesis in the mesenteric artery and the low level of hypothalamic norepinephrine concentration may participate in the development of 2K-1C hypertension in rats. PMID- 2902049 TI - Viewpoint: let's hear it for good eating. AB - Health care professionals need to look more closely at the nutritional content of the meals they serve at meetings and other functions. PMID- 2902051 TI - DNA polymorphism in the human Thy-1 gene. AB - Thy-1 is a membrane glycoprotein expressed predominantly in brain tissue and occasionally in lymphoid tissue. The human Thy-1 gene is located on chromosome 11q22.3. Although two allelic forms of Thy-1 exist in mice (Thy-1.1 and Thy-1.2), no allelic forms have been described for the human Thy-1 gene. We describe a polymorphic MspI site within the human Thy-1 gene that distinguishes two alleles, 8 and 9, which are represented in a northern European population at frequencies of 0.7 and 0.3, respectively. Thy-1, therefore, provides a potentially useful marker to identify linkages with human disease genes located near 11q22. PMID- 2902050 TI - In situ hybridization using 32P labelled oligodeoxyribonucleotides for the cellular localisation of mRNA in neuronal and endocrine tissue. An analysis of procedural variables. AB - Methodological variables for in situ hybridization using 32P labelled oligodeoxyribonucleotides (oligomers) have been examined. Four different oligomers directed against proglucagon messenger RNA (mRNA) and two different oligomers against prosomatostatin mRNA have been used. Specific hybridization was obtained in adult rat brain, stomach and pancreas and in neonatal rat ileum. Tissue was perfusion fixed with 4% paraformaldehyde 0.2% glutaraldehyde and hybridization was carried out in 50% formamide for 72 h at 42 degrees C. Using hybridization conditions of lower stringency (33% formamide) labelling was also obtained in guinea pig tissue. Other variables which affected hybridization signal intensity were the inclusion of a prehybridization dehydration stage, the probe concentration, the inclusion of ammonium acetate in the posthybridization dehydrating ethanols and in the autoradiographic emulsion, and the exposure time. The localisation of proglucagon mRNA in rat pancreas using a 20mer was used as a model tissue for testing these methodological variables and the results were found generally also to apply to the other probes and tissues tested. The methods described provide single cell resolution and show that 32P labelled oligomers may be used to localise neuropeptide and endocrine mRNAs in different types of tissue and in different mammalian species. PMID- 2902052 TI - Correlations between polymorphisms at the DNA and at the protein level of DRw52 haplotypes, revealed with a variety of techniques. AB - LB-Q1 and LB-Q4 are two subtypes of DRw52, defined by proliferative T-cell clones. These subtypes represent a polymorphism of the DR beta III gene. Similar subtypes of DRw52 can be defined by oligonucleotide typing, serology and RFLP analysis. In the present study we compared these typing techniques on a panel of 22 HLA-D homozygous, DRw52-positive typing cells. All typing techniques correlated very well. Three subtypes of DRw52 could be identified. Our results show that typing for cellularly defined structures can be done with a variety of noncellular techniques. This observation has important implications for matching in unrelated bone marrow transplantation and for disease association studies. PMID- 2902053 TI - Human immunoglobulin heavy-chain-variable (VH) region gene families defined by hybridization with cloned human and murine VH-genes. AB - The Southern DNA hybridization technique was used to determine the organization of human immunoglobulin heavy-chain-variable region (VH) gene families and the extent of polymorphism within these families. Human DNA was digested with a restriction enzyme and then hybridized to a cloned human or murine VH gene. Six human and six murine genes were used. Hybridization patterns seen in the human genes fell into three groups, which corresponded to the Kabat subgroup assignments based on sequence. When DNA from different individuals was compared, polymorphism was demonstrated in each of the three gene families. The VH II family demonstrated a higher degree of polymorphism than the others. Hybridization with the murine probes, each of which represented a different murine VH-gene family, revealed six distinct patterns of hybridization. Five of the probes detected all or a portion of one of the previously defined human families. The sixth probe, 36-60, yields a unique pattern of hybridization, suggesting a fourth VH-gene family. Dot hybridizations show that 36-60 does not hybridize with human VH-genes representing each of the known families, further supporting this possibility. PMID- 2902054 TI - Ciguatera fish poisoning. PMID- 2902055 TI - Medical necessity denial and refund letters. PMID- 2902056 TI - Why invest in continuing education? PMID- 2902057 TI - Modern stereotactic neurosurgery. PMID- 2902058 TI - Following microdiskectomy. Laceration of the abdominal aorta and vena cava. PMID- 2902059 TI - Unsuspected bilateral ureteral transitional carcinoma. PMID- 2902061 TI - The viewbox. Juvenile laryngeal papillomatosis. PMID- 2902060 TI - Congenital left atrial aneurysm. PMID- 2902062 TI - Talk about mysteries. PMID- 2902064 TI - The evolution of otitis media treatment in Illinois. PMID- 2902063 TI - Surgery of the ascending thoracic aorta. PMID- 2902065 TI - Abdominal aortic aneurysm repair. PMID- 2902066 TI - Moonlight and Champaign. PMID- 2902067 TI - Takayasu's arteritis. Protean manifestations. AB - An adolescent girl presented with fever, weight loss, and headache. Despite extensive diagnostic studies, the diagnosis of Takayasu's arteritis was made only after she developed bruits and diminished pulses. Although the initial manifestations of Takayasu's arteritis are often protean and confusing, characteristic clinical and radiographic findings develop after the onset of vascular insufficiency. The chest radiograph may provide an early clue to diagnosis, which can be confirmed by arterial digital subtraction aortography. Physicians should consider Takayasu's arteritis in the differential diagnosis of prolonged fever or weight loss in young females because treatment appears to be more effective when started early. PMID- 2902068 TI - DNA polymorphism in strains of the genus Brucella. AB - Preparations of DNA from 23 Brucella strains including 19 reference strains were compared by restriction endonuclease analysis. Pulsed-field gel electrophoresis resulted in optimal resolution of fragments generated by digestion with low cleavage-frequency restriction enzymes such as XbaI. By this technique, five electrophoretypes were distinguished in five reference strains of the different species, i.e., B. abortus, B. melitensis, B. suis, B. canis, and B. ovis. Minor profile differences allowed us to discriminate between most biovars within a species. However, the differences in the DNA patterns of different field strains of biovar 2 of B. melitensis were not sufficient to serve as markers for epidemiological studies. From the XbaI fragments, we were able to estimate the size of the genomes of B. abortus 544T and B. melitensis 16 MT. This method revealed a relationship between DNA fingerprints, species, and pathovars which could shed light on problems concerning the classification and evolution of members of the genus Brucella. PMID- 2902069 TI - Molecular characterization of a gene encoding a 72-kilodalton mosquito-toxic crystal protein from Bacillus thuringiensis subsp. israelensis. AB - A gene encoding a 72,357-dalton (Da) crystal protein of Bacillus thuringiensis var. israelensis was isolated from a native 75-MDa plasmid by the use of a gene specific oligonucleotide probe. Bacillus megaterium cells harboring the cloned gene (cryD) produced significant amounts of the 72-kDa protein (CryD), and the cells were highly toxic to mosquito larvae. In contrast, cryD-containing Escherichia coli cells did not produce detectable levels of the 72-kDa CryD protein. The sequence of the CryD protein, as deduced from the sequence of the cryD gene, was found to contain regions of homology with two previously described B. thuringiensis crystal proteins: a 73-kDa coleopteran-toxic protein and a 66 kDa lepidopteran- and dipteran-toxic protein of B. thuringiensis subsp. kurstaki. A second gene encoding the B. thuringiensis subsp. israelensis 28-kDa crystal protein was located approximately 1.5 kilobases upstream from and in the opposite orientation to the cryD gene. PMID- 2902070 TI - Escherichia coli F41 adhesin: genetic organization, nucleotide sequence, and homology with the K88 determinant. AB - The genetic organization of the polypeptides required for the biosynthesis of the F41 adhesin of enterotoxigenic Escherichia coli strains was investigated. Maxicell analysis demonstrated that a recombinant plasmid which mediated mannose resistant hemagglutination and F41 antigen production encoded four polypeptides of 29, 30, 32, and 86 kilodaltons. The 29-kilodalton protein was identified as the F41 antigen, and the nucleotide sequence of the gene was determined. Extensive homology was observed between the region encoding the putative signal sequences of the F41 and K88 antigens and in the region immediately upstream of the antigen genes. The nucleotide sequence homology between F41 and K88 determinants was further investigated by Southern blot hybridization. A K88 probe hybridized at high stringency to all fragments shown to be essential for F41 production except for fragments internal to the F41 antigen gene. PMID- 2902071 TI - Benzodiazepine withdrawal: a review of the evidence. AB - In a recent series of controlled studies, investigators looked at what happened when benzodiazepines were discontinued. Despite methodological problems, these studies showed that rebound anxiety occurred in a substantial minority of patients after several weeks of drug use. Also, a withdrawal syndrome developed in nearly half of patients who used benzodiazepines for more than a year. In these studies, risk factors included dose, duration of use, elimination rate of the drug, and abruptness of discontinuation. Patients who are physically dependent on benzodiazepines may need help in stopping these agents. Physicians should advise gradual discontinuation and, along with emotional support, should consider the use of alternative medications for the control of symptoms. PMID- 2902072 TI - Reevaluation of chronically ill psychiatric patients. PMID- 2902073 TI - Rubredoxin as an intermediary electron carrier for nitrate reduction by NAD(P)H in Clostridium perfringens. AB - The NAD(P)H-dependent nitrate reductase system in Clostridium perfringens was reconstituted with rubredoxin (Rd), nitrate reductase (NaR), and an unadsorbed fraction, on a DEAE-cellulose column, of the extract (designated as fraction A), under nitrogen gas. Ferredoxin in place of Rd was not effective as an electron carrier in this reconstituted system. NAD(P)H-dependent nitrate reducing activity was also obtained by replacing fraction A with ferredoxin-NADP+ reductase from spinach. We propose the following scheme for the electron transfer in this NAD(P)H dependent nitrate reduction system. NAD(P)H----NAD(P)H-Rd reductase----Rd ---NaR----NO3-. PMID- 2902074 TI - A single autosomal gene controlling the expression of the extended globoglycolipid carrying SSEA-1 determinant is responsible for the expression of two extended globogangliosides. AB - Two extended globogangliosides, designated as Z1 and Z2, were purified from the kidney of DBA/2 mice. By means of GLC, 1H-NMR spectroscopy, negative-ion fast atom bombardment mass spectrometry, methylation analysis, and enzymatic digestion, the structures of Z1 and Z2 were determined to be NeuGc alpha 2-3Gal beta 1-3GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1-Cer and NeuGc alpha 2 8NeuGc alpha 2-3Gal beta 1-3GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1 Cer, respectively. Since Z1 and Z2 were not detectable in the kidney of C57BL/10 and 6, BALB/c, and WHT/Ht mice, the mode of genetic control on Z1 and Z2 expression was examined by mating experiments between C57BL/10 or BALB/c and DBA/2. The results indicated that the expression of Z1 and Z2 is a recessive phenotype and that DBA/2 mice carry a single autosomal recessive gene. In the previous paper, we reported that DBA/2 mice do not express GL-Y (Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-6(Gal beta 1-3)Gb4Cer) but express GL-X (Gal beta 1 3Gb4Cer) in the kidney (J. Biochem. 101, 553-562 (1987)), and that a single autosomal defective gene responsible for the defective GL-Y expression was identified by genetic analysis (J. Biochem. 101, 563-568 (1987)).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902075 TI - Structure of the human tyrosine hydroxylase gene: alternative splicing from a single gene accounts for generation of four mRNA types. AB - Tyrosine hydroxylase (TH) is a rate-limiting enzyme for catecholamine biosynthesis. Recently, Grima et al. (Nature (1987) 326, 707-711) and we (Biochem. Biophys. Res. Commun. (1987) 146, 971-975; Nucleic Acids Res. (1987) 15, 6733) reported four similar but distinct mRNAs that encode human TH. These mRNAs are constant for the major part, but are distinguishable from one another as to the insertion/deletion of 12-bp and 81-bp sequences near the N-terminus. We isolated genomic clones encoding the human TH gene and determined the nucleotide sequence. The human TH gene is split into 14 exons. The 12-bp insertion sequence is encoded by the 3'-terminal portion of the first exon. The 81-bp insertion sequence corresponds to the second exon. Taking into consideration also the results of Southern blot analysis of human genomic DNA, we concluded that the four types of human TH mRNA are produced through alternative splicing from a single gene. Two kinds of alternative splicing are involved: the alternative use of two donor sites in the first exon, and the inclusion/exclusion of the second exon. We propose a possible secondary structure for the latter alternative splicing pathway. PMID- 2902076 TI - Decrease of hypothalamic TRH levels but not plasmatic TSH levels after ablation of submandibular salivary glands in the rat. AB - Indirect relationships are thought to exist between submandibular salivary glands (SSG) and the central nervous system (CNS) via superior cervical ganglia (SCG). To study this topic, the concentrations of thyrotropin releasing hormone (THR) and somatostatin (SRIF) were measured in both whole and specific areas of the hypothalamus, as well as plasmatic thyrotropin stimulating hormone (TSH) levels following ablation of SSG. Twenty, forty and fifty days after ablation of SSG, groups of operated and sham-operated animals weighing 230-260 g at the beginning of experimentation, were killed by cervical dislocation. Plasma was taken, frozen and stored for TSH-radioimmunoassay (RIA) and the hypothalami were removed and homogenized in either 0.1 N HCl (for TRH-RIA) or 0.2 N acetic acid (for SRIF RIA). Twenty days after ablation of SSG in another group, TRH concentrations were measured in both the median eminence (ME) and the paraventricular nucleus (PVN), dissected by the micropunch technique. The results show that twenty days after SSG ablation, the hypothalamic TRH concentrations was significantly lower in operated than in sham-operated animals (295.2 +/- 24.8 vs 226 +/- 11.15 pg/mg hypothalamus respectively p less than 0.01, n = 9). No differences were observed at later intervals. This finding seems to be specific for this peptide since the SRIF level was not modified twenty days after SSG removal. Among the discrete hypothalamic areas examined, only the ME exhibited a significant decrease in TRH content (25.43 +/- 3.02 ng/mg prot. VS. 41.24 +/- 1.33 ng/mg prot., respectively). Despite these results on TRH levels, no modifications in plasmatic TSH levels were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902077 TI - Dissociation of fibrinogen and fibronectin binding from transglutaminase-mediated cross-linking at the hepatocyte surface. AB - The interaction of fibrinogen and fibronectin with hepatocytes has been dissociated into distinct binding and cross-linking steps. Binding and cross linking of 125I-labeled ligands were both decreased by transglutaminase inhibitors, but not by heparin or hirudin. Transglutaminase activity was manifest by Ca2+-dependent incorporation of [14C]putrescine into cells. Preferential cross linking of fibrinogen A alpha over gamma chains, and lack of inhibition by heparin or hirudin indicates the involvement of tissue transglutaminase, and not Factor XIIIa. Hepatic transglutaminase activity, as well as binding and cross linking of fibrinogen and fibronectin, were maximally supported by Ca2+, partially supported by Mn2+ and Sr2+, and markedly decreased by Mg2+ and Ba2+. In contrast, Co2+ supported binding but not cross-linking or transglutaminase activity, indicating that binding and cross-linking are dissociable events. This conclusion was corroborated by the finding that fibrinogen fragments D95 and D78 both inhibited Ca2+-dependent fibrinogen binding without being cross-linked themselves. Ligand binding in the presence of either cation was localized to the cell surface as evidenced by its trypsin sensitivity. Thus, fibrinogen and fibronectin binding to hepatocytes is independent of transglutaminase activity, whereas cross-linking of these adhesive macromolecules requires an enzymatically active cellular transglutaminase. In addition, fibrinogen binding appears to be mediated by molecular determinants present in fragment D78. PMID- 2902078 TI - On the location and function of the noncatalytic sites on the bovine heart mitochondrial F1-ATPase. AB - Modification of Tyr-345 at a catalytic site in a single beta subunit of the bovine heart mitochondrial F1-ATPase (MF1) by 5'-p-fluorosulfonylbenzoylinosine did not affect subsequent labeling of noncatalytic sites at Tyr-368 and His-427 in three copies of the beta subunit by 5'-p-fluorosulfonylbenzoyladenosine (FSBA). These results clearly show that the beta subunit contains at least parts of the catalytic and noncatalytic nucleotide binding sites. Inactivation of MF1 by 96% with FSBA was accompanied by a decrease in the endogenous ADP content from 1.86 to 0.10 mol per mol of MF1. Decrease in the endogenous ADP content during the inactivation of the enzyme with FSBA paralleled loss in activity in a manner which suggests that the reaction of FSBA with an open noncatalytic site promoted release of ADP from another noncatalytic site until the third site reacted with FSBA. Two pKa values of about 5.9 and 7.6 were observed on the acid side of the pH optimum in the pH-rate profile for ATP hydrolysis catalyzed by MF1 in neutral acid buffers. In contrast, a single pKa of 5.9 was present in the pH-rate profile for ITP hydrolysis catalyzed by the enzyme in the same buffers. The augmented rate observed for ATP hydrolysis at pH 8.0, over that observed at pH 6.5, was lost as the enzyme was inactivated by FSBA in a manner suggesting that modulation is lost as the third noncatalytic site is modified. This suggests that ATP hydrolysis by MF1 is modulated in a pH-dependent manner by ATP binding to an open noncatalytic site. Two other modulations associated with binding of adenine nucleotides to noncatalytic sites, ADP-induced hysteretic inhibition and apparent negative cooperativity reflected by the Hill coefficient for the hydrolysis of 50 3000 microM ATP at pH 8.0, also disappeared as the third noncatalytic site reacted with FSBA. PMID- 2902079 TI - Mutations of the yeast plasma membrane H+-ATPase which cause thermosensitivity and altered regulation of the enzyme. AB - Four random mutations of the plasma membrane H+-ATPase of Saccharomyces cerevisiae which result in thermosensitive growth have been sequenced. All of the mutations map in regions conserved by the family of ATPases which form a phosphorylated intermediate. The Gly254----Ser mutation affects a glycine residue conserved in all of the sequenced ATPases. The Thr212----Ile and Ala547----Val mutations do not affect conserved amino acids, but their replacements are not found in any of the sequenced ATPases. Thr212 and Gly254 occur in the proposed phosphatase domain, whereas Ala547 is located within the putative ATP-binding site. The other mutation is a double change (Asp91----Tyr and Glu92----Lys) in the N-terminal domain, in which the altered glutamate is conserved in fungal and protozoan H+-ATPases. Proton efflux from whole cells and ATP hydrolysis by purified plasma membranes are more thermolabile in cells carrying the ATPase mutations than in wild-type yeast. Therefore, the defects in growth and proton transport at the nonpermissive temperature can be attributed to impairment of ATPase activity. Incubation of wild-type yeast cells with glucose before homogenization induces changes in the specific activity, Km, pH optimum, and vanadate sensitivity of the plasma membrane ATPase. The Ala547----Val mutation results in an enzyme from starved cells with the kinetic parameters of the glucose-activated wild-type ATPase. Therefore, a single amino acid change mimics the poorly understood regulatory mechanism triggered by glucose. PMID- 2902080 TI - Alteration of the nucleotide-binding site asymmetry of chloroplast coupling factor 1 by catalysis. AB - Fluorescence resonance energy transfer was used to show that ATP hydrolysis induces a change in the properties of two nucleotide-binding sites in isolated chloroplast coupling factor 1 (CF1). The fluorescence donor was Lucifer Yellow vinyl sulfone (4-amino-N-[3-(vinylsulfonyl)phenyl]naphthalimide- 3,6 disulfonate), covalently bound to a unique site on the alpha subunit between nucleotide-binding sites 2 and 3. The fluorescence acceptor was the ATP analog 2'(3')-trinitrophenyladenosine 5'-triphosphate (TNP-ATP), incorporated specifically into nucleotide-binding site 1. Energy transfer from Lucifer Yellow to TNP-ATP in site 1 was greater if catalysis occurred before TNP-ATP was incorporated than if no catalysis occurred, indicating that one of the nucleotide binding sites near the Lucifer Yellow had changed its properties to those of site 1 as a result of catalysis. The amount of energy transfer increased with the degree of substrate excess during catalysis, as expected if catalysis were required for the new site 1 location. ADP, which binds to CF1, but is not a substrate for hydrolysis, caused little energy transfer. Titration of site 3 with TNP-ATP showed greater energy transfer from Lucifer Yellow when catalysis had not occurred, indicating that sites 1 and 3 switched properties as a result of catalysis. The amount of energy transfer declined exponentially with time between removal of substrate and addition of TNP-ATP to site 1, with a half-time of 1.5-2 h at room temperature. This result suggests that the change that results in switching of nucleotide-binding sites 1 and 3 relaxes in the absence of substrate. Our results show that the asymmetry of the nucleotide-binding sites of CF1 is not a permanent feature of the molecule. PMID- 2902081 TI - The binding sites on fibrin(ogen) for guinea pig liver transglutaminase are similar to those of blood coagulation factor XIII. Characterization of the binding of liver transglutaminase to fibrin. AB - The present study represents detailed investigations into the nature of interactions between an intracellular "tissue" transglutaminase and a plasma protein, fibrinogen. We demonstrate a specific, saturable, and reversible binding of transglutaminase to fibrin(ogen). The binding was time- and temperature dependent, was independent of divalent metal ions, did not require the release of either fibrinopeptide A or B, and was partially inhibited by the presence of sodium chloride or plasma proteins, properties similar to Factor XIII binding to fibrin(ogen). Both Factor XIII and liver transglutaminase also shared similar binding sites on fibrinogen, the A alpha- and the B beta-chains. The binding characteristics of liver transglutaminase were thus similar to Factor XIII binding to fibrin, but there were also important differences. Scatchard analyses of the binding data indicated that the affinity of liver transglutaminase (Kd = 4.17 x 10(-7) M) was at least 40-fold weaker compared with the affinity of Factor XIII to fibrinogen. Consequently, a 20-fold molar excess of Factor XIII a-chains specifically and completely inhibited the binding of liver transglutaminase to des-A-fibrinogen. The association between liver transglutaminase and fibrin(ogen) was also critically controlled by the conformational states of the two proteins. Substances capable of altering the conformation of either transglutaminase (such as guanosine 5'-triphosphate) or of fibrinogen (such as the tetrapeptide Gly-Pro Arg-Pro and Fragment D) disrupted binding. Excess CaCl2 was able to counteract the effects of guanosine 5'-triphosphate on transglutaminase binding to fibrin. In contrast, Factor XIII binding to fibrin was unaffected by either guanosine 5' triphosphate, CaCl2, or Gly-Pro-Arg-Pro, suggesting a more stable association between the two proteins. The physiologic implications of transglutaminase fibrin(ogen) interactions are discussed. PMID- 2902082 TI - Somatostatin receptors on rat cerebrocortical membranes. Structural characterization of somatostatin-14 and somatostatin-28 receptors and comparison with pancreatic type receptors. AB - Somatostatin binding and cross-linking to its receptors on rat cerebrocortical membranes were characterized with [125I-Tyr1]somatostatin-14 and [125I-Leu8, D Trp22, Tyr25]somatostatin-28. When [125I-Tyr1]somatostatin-14 was cross-linked to its receptors with the photoreactive cross-linker, N-(5-azido-2 nitrobenzoyloxy)succinimide, the hormone was specifically associated with a Mr = 72,000 protein band in the presence or absence of reducing agents. Affinity labeling of the Mr = 72,000 protein band was decreased with increasing concentrations of unlabeled somatostatin-14 and nonhydrolyzable guanine nucleotide analog, guanyl-5'-yl imidodiphosphate (Gpp(NH)p). Pretreatment of cerebrocortical membranes with islet-activating protein resulted in a decrease in subsequent labeled somatostatin-14 binding and affinity-labeling of the protein and abolished an inhibitory effect of somatostatin-14 on vasoactive intestinal peptide-stimulated increase in adenylate cyclase activity. When the affinity labeled protein was solubilized with Zwittergent 3-12 and adsorbed to wheat germ agglutinin-agarose, it was eluted by N-acetylglucosamine. [125I-Leu8, D-Trp22, Tyr25]somatostatin-28 cross-linking to cerebrocortical and pancreatic membranes with the same photoreactive agent revealed specifically labeled protein bands of a Mr = 74,000 in cerebrocortical membranes and a Mr = 94,000 in pancreatic membranes, respectively. These results suggest that: 1) somatostatin receptor on cerebrocortical membranes is a monomeric glycoprotein with a Mr = 70,000 binding subunit, coupled to guanine nucleotide regulatory protein, and 2) the Mr = 70,000 protein may be a common receptor for somatostatin-28 and somatostatin-14 and is distinct from a common pancreatic type receptor. PMID- 2902083 TI - Delta subunit of chloroplast coupling factor 1 inhibits proton leakage through coupling factor O. AB - The ATP synthase of chloroplasts consists of a proton-conducting portion, CF0, and a catalytic portion, CF1. The smaller subunits of CF1, in particular delta, may play a key role in the coupling of proton transport to ATP synthesis. Purified subunit delta, when added to partially CF1-depleted thylakoid membranes, can restore photophosphorylation (Engelbrecht, S., and Junge, W. (1987) Eur. J. Biochem. 172, 213-218). We report here that it does so by blocking proton conduction through CF0. Thylakoids were CF1-depleted by incubation in hypoosmolar NaCl/EDTA solutions. Variation of the NaCl concentrations and of the incubation times not only changed the overall degree of CF1 depletion but also the subunit composition of solubilized CF1, namely CF1 containing delta and CF1(-delta). This was quantified by immunoelectrophoresis and by fast protein liquid chromatography. Proton conduction was measured by flash spectrophotometry by using standard electrochromic and pH-indicating absorption changes. The removal of integral CF1 was correlated with high electric conductance of thylakoid membranes, an increased extent of rapid proton leakage, and loss of ATP synthesis activity, which exceeded the percentual loss of CF1. The removal of predominantly CF1(-delta) resulted in comparatively lesser effects on the loss of ATP synthesis and on the extent and velocity of proton leakage. On the same line, addition of integral CF1 and of purified delta diminished the electric leak in CF1-depleted thylakoids. Both approaches, the controlled removal of CF1 and CF1(-delta), respectively, and addition of delta and CF1 showed that delta can act as a "stopcock" to the exposed proton channel CF0. PMID- 2902084 TI - Biosynthesis of the plasma membrane H+-ATPase of Neurospora crassa. AB - The plasma membrane H+-ATPase of Neurospora is a 100-kDa integral membrane protein which appears, on the basis of hydropathy analysis of its amino acid sequence, to span the lipid bilayer at least eight times. To investigate the assembly and processing of the ATPase, a full-length cDNA has been constructed for use in in vitro transcription and translation experiments. Comparison of three different forms of the ATPase (nascent protein, nascent protein cotranslationally inserted into membranes, and mature protein) revealed no difference in electrophoretic mobility. Furthermore, the nascent and mature forms gave identical peptide patterns after partial proteolysis with Staphylococcus aureus V8 protease, suggesting that the ATPase does not contain an NH2-terminal signal peptide which is cleaved upon membrane insertion. Consistent with this interpretation, the NH2-terminal peptide has been purified from a tryptic digest of the ATPase and found to lack only the initiator methionine residue; the penultimate alanine is acetylated based on analysis by fast atom bombardment mass spectroscopy. Although the ATPase contains one potential site of N-linked glycosylation, its electrophoretic mobility was unchanged following digestion with endoglycosidase H and it did not incorporate [3H]mannose or bind concanavalin A. Thus, the Neurospora plasma membrane-ATPase appears to undergo minimal post-translational processing, and its membrane insertion is probably mediated by internal sequences. PMID- 2902086 TI - Characterization of six nucleotide-binding sites on chloroplast coupling factor 1 and one site on its purified beta subunit. AB - By using gel filtration chromatography, following the technique of Hummel and Dreyer (Hummel, J., and Dreyer, W. (1962) Biochim. Biophys. Acta 63, 532-534), the adenine nucleotide-binding sites of isolated soluble chloroplast ATPase (CF1) and of the beta subunit were studied. CF1 possesses six adenine nucleotide binding sites: two high affinity sites for ADP or ATP (KdH = 1-5 microM) in addition to one site where endogenous not-exchangeable ADP is bound, and three low affinity sites binding ADP or ATP with a dissociation constant (KdL = 15-20 microM) which is considerably increased in the presence of pyrophosphate. KdH is not modified by addition of pyrophosphate. The stability of nucleotide binding at the low affinity sites increases after heat activation of CF1. Removal of the delta or epsilon subunits on CF1 affects neither the number nor the binding parameters of the nucleotide-binding sites. The purified beta subunit possesses one easily exchangeable site/subunit. It is proposed that the low affinity sites on CF1 are the catalytic sites. PMID- 2902085 TI - Phorbol ester and neomycin dissociate bradykinin receptor-mediated arachidonic acid release and polyphosphoinositide hydrolysis in Madin-Darby canine kidney cells. Evidence that bradykinin mediates noninterdependent activation of phospholipases A2 and C. AB - Many types of peptide hormone and neurotransmitter receptors mediate hydrolysis of phosphoinositides (PI) and arachidonic acid and arachidonic acid metabolite (AA) release, but the relation between these responses is not clearly defined. We have characterized bradykinin (BK)-mediated AA release and PI hydrolysis in clonal Madin-Darby canine kidney cells (MDCK-D1). Both responses occurred over a similar dose range in response to the B1 and B2 receptor agonist, BK, but not in response to the B1 receptor-selective agonist des-Arg-BK. To test whether AA release occurs via a mechanism which is sequential to and dependent upon PI hydrolysis, we used the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), which activates protein kinase C. TPA treatment blocked BK-mediated PI hydrolysis in MDCK-D1 cells, while at the same time and at similar concentrations enhancing BK-mediated AA release. Thus, TPA treatment dissociated BK-mediated AA release from PI hydrolysis. In addition, treatment of MDCK-D1 cells with neomycin blocked BK-mediated hydrolysis of phosphatidylinositol bisphosphate without reducing BK-mediated AA release. BK treatment increased formation of lysophospholipids with a time course in accord with BK-mediated AA release, indicating that at least part of the BK-mediated AA release was likely derived from activation of phospholipase A2. BK-mediated lysophospholipid production was enhanced by pretreatment with TPA, suggesting that the mechanism of AA release before and after treatment with TPA was the same. BK-mediated AA release and lysophospholipid production was dependent on the presence of extracellular calcium, while the enhanced responses to BK in the presence of TPA were not dependent on the presence of extracellular calcium. TPA treatment also enhanced AA release and lysophospholipid production in response to the calcium ionophore A23187. From these data we propose that BK, acting at B2 receptors, promotes AA release in MDCK cells via a mechanism which is 1) independent of polyphosphoinositide hydrolysis by phospholipase C, 2) dependent upon influx of extracellular calcium and activation of phospholipase A2, and 3) enhanced by activation of protein kinase C. PMID- 2902087 TI - Structure of the human neutrophil elastase gene. AB - The gene for human neutrophil elastase (NE), a powerful serine protease carried by blood neutrophils and capable of destroying most connective tissue proteins, was cloned from a genomic DNA library of a normal individual. The NE gene consists of 5 exons and 4 introns included in a single copy 4-kilobase segment of chromosome 11 at q14. The coding exons of the NE gene predict a primary translation product of 267 residues including a 29-residue N-terminal precursor peptide and a 20-residue C-terminal precursor peptide. Analysis of the N-terminal peptide sequence suggests it contains a 27-residue "pre" signal peptide followed by a "proN" dipeptide, similar to that of other blood cell lysosomal proteases. The sequences for the mature 218-residue NE protein are included in exons II-V. The 5'-flanking region of the gene includes typical TATA, CAAT, and GC sequences within 61 base pairs (bp) of the cap site. The sequence 1.5 kilobases 5' to exon I contains several interesting repetitive sequences including six tandem repeats of unique 52- or 53-bp sequences. The 5'-flanking region also contains a 19-bp segment with 90% homology to a segment of the 5'-flanking region of the human myeloperoxidase (MPO) gene, a gene also expressed in bone marrow precursor cells and a protein stored in the same neutrophil granules as NE. In addition, like the MPO gene, the NE 5'-flanking region has several regions with greater than or equal to 75% homology to sequences 5' to c-myc, but there is no overlap between the NE-c-myc and MPO-c-myc homologous sequences. PMID- 2902088 TI - ATP synthesis is driven by an imposed delta pH or delta mu H+ but not by an imposed delta pNa+ or delta mu Na+ in alkalophilic Bacillus firmus OF4 at high pH. AB - Starved whole cells of alkalophilic Bacillus firmus OF4 that are equilibrated at either pH 10.2, 9.5, or 8.5 synthesize ATP in response to a pH gradient that is imposed by rapid dilution of the cyanide-treated cells into buffer at pH 7.5. If a valinomycin-mediated potassium diffusion potential (positive out) is generated simultaneously with the pH gradient, then the rate of ATP synthesis and the level of synthesis achieved is much higher than upon imposition of a pH gradient alone. By contrast, imposition of a large chemical gradient of Na+, either in the presence or absence of a concomitant diffusion potential, fails to result in ATP synthesis. We conclude that this organism does not possess a sodium-motive ATPase that can be made to synthesize detectable levels of ATP by imposition of a suitably large chemical or electrochemical gradient of Na+. On the other hand, a proton-translocating ATPase is in evidence when protons are provided at very high pH, corroborating our earlier work on extremely alkalophilic bacilli. Oxidative phosphorylation must, then, be catalyzed in these organisms by a proton translocating ATPase even though the putative bulk driving forces for such a catalyst are low under optimal growth conditions. Stable, imposed pH gradients of 1 unit, comparable to the magnitude of the total electrochemical proton gradient of growing cells, result in much lower ATP concentrations than observed in such cells. We hypothesize that ATP synthesis in growing cells utilizes protons that are made available by some localized pathway between proton pumps and the ATP synthase. PMID- 2902089 TI - Identification of tryptic cleavage sites for two conformational states of the Neurospora plasma membrane H+-ATPase. AB - Previous work has shown that the tryptic degradation pattern of the Neurospora plasma membrane H+-ATPase varies with the presence and absence of ligands, thus providing information about conformational states of the enzyme (Addison, R., and Scarborough, G. A. (1982) J. Biol. Chem. 257, 10421-10426; Brooker, R. J., and Slayman, C. W. (1983) J. Biol. Chem. 258, 8827-8832). In the present study, sites of tryptic cleavage have been mapped by immunoblotting with N- and C-terminal specific antibodies and by direct sequencing of proteolytic products after electro-transfer to polyvinylidene difluoride filters. In the absence of ligands (likely to represent the E1 conformation), trypsin cleaved the 100-kDa ATPase polypeptide at three sites very near the N terminus: Lys-24, Lys-36, and Arg-73. Removal of the first 36 amino acid residues only slightly affected ATPase activity, but removal of the subsequent 37 residues inactivated the enzyme completely. In the presence of vanadate and Mg2+ (E2 conformation), the rate of trypsinolysis at Arg-73 was greatly reduced, and enzyme activity was protected. In addition, a new cleavage site near the C terminus (Arg-900) became accessible to trypsin. Both effects of vanadate occurred at micromolar concentrations, well within the range previously measured for vanadate inhibition of ATPase activity. Taken together, these results suggest that the Neurospora ATPase undergoes significant conformational changes at both termini of the polypeptide during its reaction cycle. PMID- 2902090 TI - Secretion of somatostatin by Saccharomyces cerevisiae. Correct proteolytic processing of pro-alpha-factor-somatostatin hybrids requires the products of the KEX2 and STE13 genes. AB - Somatostatin is a 14-amino-acid peptide hormone that is proteolytically excised from its precursor, prosomatostatin, by the action of a paired-basic-specific protease. Yeast (Saccharomyces cerevisiae Mat alpha) synthesizes an analogous peptide hormone precursor, pro-alpha-factor, which is proteolytically processed by at least two separate proteases, the products of the KEX2 and STE13 genes, to generate the mature bioactive peptide. Expression in yeast of recombinant DNAs encoding hybrids between the proregion of alpha-factor and somatostatin results in proteolytic processing of the chimeric precursors and secretion of mature somatostatin. To determine if the chimeras were processed by the same enzymes that cleave endogenous pro-alpha-factor, the hybrid DNAs were introduced into kex2 and ste13 mutants, and the secreted proteins were analyzed. Expression of the pro-alpha-factor-somatostatin hybrids in kex2 mutant yeast resulted in secretion of a high molecular weight hyperglycosylated precursor. No mature somatostatin was secreted, and there was no proteolytic cleavage at the Lys-Arg processing site. Similarly, in ste13 yeast, only somatostatin molecules containing the (Glu-Ala)3 spacer peptide at the amino terminus were secreted. Our results demonstrate that in yeast processing mutants, the behavior of the chimeric precursors with respect to proteolytic processing was exactly as that of endogenous pro-alpha-factor. We conclude that the same enzymes that generate mature alpha-factor proteolytically process hybrid precursors. This suggests that structural domains of the proregion rather than the mature peptide are recognized by the processing proteases. PMID- 2902091 TI - Glutamate uptake by brain synaptic vesicles. Energy dependence of transport and functional reconstitution in proteoliposomes. AB - The dependence of glutamate uptake on ATP-generated proton electrochemical potential was studied in a highly purified preparation of synaptic vesicles from rat brain. At low chloride concentration (4 mM), the proton pump present in synaptic vesicles generated a large membrane potential (inside-positive), associated with only minor acidification. Under these conditions, the rate of L [3H]glutamate uptake was maximal. In addition, L-glutamate induced acidification of the vesicle interior. D-Glutamate produced only 40% of the effect, and L aspartate or gamma-aminobutyric acid produced less than 5%. The initial rate of glutamate-induced acidification increased with increasing glutamate concentration. It was saturable and showed first-order kinetics (KM = 0.32 mM). Correspondingly, L-glutamate induced a small reduction in the membrane potential. The rate of ATP hydrolysis was unaffected. In comparison, glutamate had no effect on acidification or membrane potential in resealed membranes of chromaffin granules. At high chloride concentration (150 mM), the vesicular proton pump generated a large pH difference, associated with a small change in membrane potential. Under these conditions, uptake of L-[3H]glutamate by synaptic vesicles was low. For reconstitution, vesicle proteins were solubilized with the detergent sodium cholate, supplemented with brain phospholipids, and incorporated into liposomes. Proton pump and glutamate uptake activities of the proteoliposomes showed properties similar to those of intact vesicles indicating that the carrier was reconstituted in a functionally active form. It is concluded that glutamate uptake by synaptic vesicles is dependent on the membrane potential and that all components required for uptake are integral parts of the vesicle membrane. PMID- 2902092 TI - Mitochondrial ATP synthase. Overexpression in Escherichia coli of a rat liver beta subunit peptide and its interaction with adenine nucleotides. AB - The C-terminal two-thirds of the rat liver ATP synthase beta subunit has been overexpressed and exported to the Escherichia coli periplasm under the direction of the alkaline phosphatase (phoA) promoter and leader peptide. The processed soluble protein contains the 358 amino acids from glutamate 122 to the rat liver beta C-terminal serine 479, including all the regions that have been predicted by chemical and genetic modification studies to be involved in nucleotide, Pi, and Mg2+ binding. Through a simple sequence of Tris/EDTA/lysozyme treatment, osmotic lysis, and alkaline pH washes, the processed beta subunit fragment can be prepared in greater than 95% purity and at a yield of greater than 20 mg/liter of culture. It interacts with 2'(3')-O-(2,4,6-trinitrophenyl) adenosine 5' triphosphate (TNP-ATP) which exhibits a strong enhancement of fluorescence upon binding. A similar enhancement is observed upon interaction with TNP-ADP. Enhancement observed with both TNP-nucleotides is markedly reduced by prior addition of either ATP or ADP and almost completely prevented by the ATP synthase inhibitor 7-chloro-4-nitrobenz-2-oxa-1,3-diazole. Both TNP-ATP and TNP-ADP bind at a stoichiometry of approximately 1 mol of nucleotide/mol of beta subunit fragment. Under the same conditions, TNP-AMP does not exhibit a fluorescence enhancement. This work demonstrates that, in the absence of interaction with other ATP synthase subunits, the rat liver beta subunit sequence from glutamate 122 to the C terminus exhibits no more than one readily detectable nucleotide binding domain. This success in producing a "functional" beta subunit fragment has significance for the pursuit of genetic and physical studies focused on the structure and function of the rat liver ATP synthase beta subunit. PMID- 2902093 TI - Cloning and sequence analysis of the human and Chinese hamster inosine-5' monophosphate dehydrogenase cDNAs. AB - Inosine-5'-monophosphate dehydrogenase, a key enzyme in the regulation of guanine nucleotide biosynthesis, was purified to homogeneity; and a polyclonal antibody directed against the purified protein was used to isolate human and Chinese hamster IMP dehydrogenase cDNA clones. These clones were sequenced and found to contain an open reading frame of a protein containing 514 amino acids. A sequence of 35 amino acids obtained by analysis of the purified protein is identical to a segment of the protein sequence deduced from the IMP dehydrogenase cDNA. The molecular mass of the deduced protein is 56 kDa, which is the observed molecular mass of the purified protein and of the immunoprecipitated in vitro translation product. Comparison of the protein sequences deduced from the human and Chinese hamster cDNA clones indicates only eight amino acid differences, suggesting that IMP dehydrogenase is a highly conserved protein. PMID- 2902094 TI - Isolation and characterization of a variant somatostatin-14 and two related somatostatins of 34 and 37 residues from lamprey (Petromyzon marinus). AB - Three major forms of somatostatin were isolated from pancreas of the lamprey (Petromyzon marinus). One of the two major forms is a 14-residue somatostatin (SS 14) having the sequence AGCKNFFWKTFSSC. The homologous substitution Ser for Thr in position 12 is the first example of SS-14 from vertebrate preprosomatostatin gene I having a divergent sequence. The longest form is 37 residues in length (SS 37) and has the sequence ALRAAAVAGSPQQLLPLGQRERKAGCKNFFWKTFSSC. A 34-residue form (SS-34) identical in sequence but truncated at a single Arg residue at position 3 of SS-37 was also isolated. The yields of the three forms were SS-37 (0.43 nmol/g), SS-34 (134 nmol/g), and SS-14 (51.5 nmol/g). The identification of this nested series of somatostatins suggests that prosomatostatin processing in lamprey more closely resembles that observed for procholecystokinin than that of mammalian or other piscine prosomatostatins. Somatostatin-producing cells in the lamprey pancreas were identified by immunostaining using antiserum against SS-34 and anti-serum against mammalian SS-14. PMID- 2902095 TI - The production and evaluation of monoclonal antibodies to Clostridium perfringens type D epsilon toxin. AB - The production of five monoclonal antibodies to the epsilon prototoxin of Clostridium perfringens is described. All five monoclonal antibodies located three proteins in a trypsinized preparation of epsilon prototoxin. These proteins were located at 37.6 kDal, 35.6 kDal and 33.7 kDal by Western blots. Two of the monoclonal antibodies, M26/2 and M27/12, neutralized epsilon toxin in the mouse lethality assay. Four of the five monoclonal antibodies are considered suitable as reagents to detect epsilon toxin in assay procedures. PMID- 2902096 TI - Adrenergic modulation of 'non-adrenergic' twitches in the rat vas deferens. AB - 1. Field stimulation of the intramural sympathetic nerves of rat vas deferens produced a biphasic contraction. Post-tetanic twitches were potentiated (PTP) and the relationship of this to the secondary component of tetanic responses was investigated. 2. A tetanus evoked by field stimulation at 4 Hz for 50 s gave a maximum increase in twitch tension of 109 +/- 5% (n = 43). The potentiation was blocked by the alpha-adrenoreceptor antagonists phenoxybenzamine, prazosin and thymoxamine. These drugs also blocked the secondary component of the tetanic response. 3. Increasing the frequency (1-8 Hz) of tetanic field stimulation enhanced the magnitude and time course of PTP. The time course of the PTP was found to depend mainly on the number of pulses in the tetanic train. 4. Reducing transmitter release in high Mg2+ solutions shortened the duration of the PTP but prevented the decline of the secondary tetanic component. Co2+ (1 mM) or Mn2+ (1 mM) mimicked the effect of high Mg2+ ions on the secondary tetanic component. Enhanced transmitter release in zero Mg2+-Krebs had the reverse effects. 5. The presynaptic alpha 2-adrenoreceptor antagonists idazoxan and yohimbine, and the neuronal uptake blockers desipramine and metaraminol, prolonged the PTP and enhanced but shortened the secondary rise in tetanic tension. 6. Bolus injections of noradrenaline before and after the tetanus gave no evidence for post-synaptic desensitization. 7. It is concluded that both the secondary rise in tetanic tension and the post-tetanic potentiation are due to an adrenergic enhancement of the 'non-adrenergic' mechanism and not, as has been supposed, to direct activation of an adrenergic tension. Thus the action of the alpha-adrenoreceptor mediated transmission is primarily one of modulation. PMID- 2902097 TI - Pre- and postjunctional beta-adrenoreceptors and hypertension. PMID- 2902098 TI - No evidence for the differential antagonism of the initial fast and secondary slow contractile responses of the rat portal vein to phenylephrine, 5 hydroxytryptamine or methacholine. AB - 1. The present study was to ascertain whether drugs cause differential antagonism of the initial fast and secondary slow contractile responses to phenylephrine, 5 HT and methacholine of the rat portal vein. 2. Cocaine (5 x 10(-6) M) had no effect on the responses to methacholine. Cocaine potentiated the initial fast but not the secondary slow responses to phenylephrine suggesting that neuronal uptake limits the initial fast but not the secondary slow response to phenylephrine. Cocaine reduced the maximal responses to 5-HT suggesting that the responses to high concentrations of 5-HT are due, in part, to the release of noradrenaline. 3. In the presence of cocaine, idazoxan had no effect on responses to phenylephrine or 5-HT and prazosin had no effect on responses to 5-HT. Prazosin (3 x 10(-9)-10( 8) M) inhibited the responses to phenylephrine causing similar parallel rightward shifts of the concentration-response curves to the initial fast and secondary slow responses. 4. In the presence of cocaine, mianserin (10(-9)-10(-8) M), cyproheptadine, (10(-10)-10(-9) M), methysergide (10(-8) M), ketanserin (10(-10) 10(-9) M) and Ly 53857 (at 10(-9)-10(-8) M) had similar inhibitory effects on the initial fast and secondary slow responses to 5-HT, namely a parallel rightward displacement of the concentration-response curves. 5. Atropine (less than or equal to 10(-7) M) and pirenzepine less than or equal to 10(-6) M) had no effect on the responses to phenylephrine and 5-HT, but caused similar parallel rightward shifts of the concentration-response curves to both responses to methacholine. 6. The results of this study provide no evidence for differential antagonism of the initial fast and secondary slow responses of the rat portal vein to phenylephrine, 5-HT or methacholine. PMID- 2902099 TI - Contractile responses of tracheal smooth muscle in organophosphate-treated swine: 1. Agonist changes. AB - 1. Male weanling swine were injected daily for up to 14 days with the organophosphate cholinesterase inhibitors, diisopropylfluorophosphate (DFP) or sarin. The clinical signs of poisoning disappeared or were attenuated by 7 days after starting the DFP treatment, indicating the development of tolerance to DFP toxicity. 2. A significant decrease in acetylcholinesterase activity (85-98%) occurred over the course of this treatment followed by a decrease in the maximal density (Bmax) of [3H] quinuclidinyl benzilate ([3H]QNB) and [3H] N methylscopolamine ([3H]-NMS) binding sites in isolated cells. The affinity of the muscarinic receptors (KD) for [3H]QNB and [3H]NMS binding, however, remained unaffected. 3. Dose-response curves for ACh-induced increase in isometric tension of tracheal smooth muscle (TSM) showed a leftward shift from control, 2 h after DFP injection. Twenty-four hours after the last DFP treatment, for animals receiving 1 or up to 14 daily injections of DFP, all the dose-response curves were shifted to the left to approximately the same ACh sensitivity when compared with that for control tissue. 4. In vitro treatment of the muscle with 10(-4) M DFP shifted the dose-response curves leftward, in both control and injected animals, and rendered the muscles from control, 1- and 3-day injected animals sensitive to ACh concentrations as low as 10(-10) M. Sensitivity to 10(-10) M ACh was eliminated by carefully cleaning the smooth muscle of adherent connective tissue containing nerves and ganglia and after subacute treatment of swine for 7 days with DFP. DFP-induced spontaneous contractions were also eliminated by careful cleaning. 5. Subacute DFP treatment caused a small leftward shift in the dose-response curve for bethanechol at 2 h and a rightward shift at 1,3 and 7 days, compared to controls. 6. Dose-response curves for K+ were shifted to the right after 1 and 3 days of DFP treatment, but shifted back towards the control after 7 days of treatment. The muscle cells were hyperpolarized by approximately 5 mV after 7 days of DFP or sarin injections. The membrane potential was slightly more sensitive to changes in K+ concentration after 7 days of sarin injection. 7. Subacute treatment of swine with organophosphates modifies the response of neural elements in swine TSM to ACh. Chronic cholinesterase inhibition causes a reduction in the sensitivity of the neural elements to ACh. The decrease in muscarinic receptor density which occurs with chronic cholinesterase inhibition is not sufficient to explain tolerance to organophosphates since TSM maintains an almost normal responsiveness to ACh. PMID- 2902100 TI - Reassessment of fluid-phase endocytosis and diacytosis in monolayer cultures of human fibroblasts. AB - We have investigated the kinetics of fluid-phase endocytosis and diacytosis in confluent monolayers of human fibroblasts by comparing the behavior of three markers that have been previously used to study this process: [14C]sucrose, 125I labeled polyvinylpyrrolidone ([125I]PVP), and Lucifer Yellow. Three distinct kinetic compartments were observed with all markers. The first was relatively large (10-60 fl/cell), reached steady state within 15 min at 37 degrees C, and was rapidly lost from monolayers after removing the markers at 37 degrees C but not at 0 degree C. These properties indicate that this compartment is the same as that previously proposed to be the major intracellular compartment involved in diacytosis. However, this compartment is probably extracellular fluid trapped between cells since it is rapidly lost into the medium when the cells are either scraped or enzymatically removed from the culture dishes at 0 degree C. In addition, it very slowly undergoes both filling and emptying at 0 degree C. However, we did observe a second, much smaller, kinetic compartment (approximately 2 fl/cell) undergoing rapid diacytosis that does seem to be intracellular. A third compartment that we observed accumulates markers at a linear rate (10-20 fl cell-1 hr-1) and is not lost from cells even after incubation periods greater than 6 hr. The markers [14C]sucrose and [125I]PVP displayed very similar behavior with respect to all three compartments and yielded nearly linear long-term uptake rates, thus indicating that there is little if any absorbed component in their uptake. However, Lucifer Yellow displayed significantly higher incorporation rates and its uptake rate was strongly nonlinear, indicating its uptake in fibroblasts is predominantly adsorptive. Our observations indicate that the rate of fluid-phase endocytosis in fibroblasts is significantly less than previously reported and that any compartment involved in diacytosis is very small and turns over very rapidly. Significantly, we estimate that the constitutive internalization of clathrin coated pits is sufficient to account for the majority of fluid-phase endocytosis and thus represents a major mechanism of membrane retrieval in these cells. PMID- 2902101 TI - Analysis of a new H2 receptor antagonist, 3-amino-5-[3-[4-(1 piperidinoindanyloxy)]propylamino]-1-methyl-1 H-1,2,4-triazole, in human plasma and urine by high-performance liquid chromatography. AB - A high-performance liquid chromatographic (HPLC) method for the determination of a new H2 receptor antagonist, 3-amino-5-[3-[4-(piperidinoindanyloxy)]propylamino] -1-methyl-1H-1,2,4-triazole (I), in human plasma and urine was developed. The method employs liquid-liquid extraction of the analyte and an internal standard and chromatographic separation using an alkylphenyl-bonded HPLC column. The total time of chromatography was less than 10 min. Sensitivity was 10 ng/ml for the plasma analysis and 1 microgram/ml for the analysis of I from urine. The coefficients of variation, based on interpolated concentrations, were less than 10%. The method was used for more than 5000 samples during clinical pharmacokinetic studies. PMID- 2902102 TI - High-performance liquid chromatographic determination of 1-(3-butoxy-2 carbamoyloxypropyl)-5-ethyl-5-phenyl-(1H,3H,5H)- pyrimidine-2,4,6-trione in human plasma. PMID- 2902103 TI - Screening procedure for the detection of alkanolamine antihistamines and their metabolites in urine using computerized gas chromatography-mass spectrometry. AB - A gas chromatographic-mass spectrometric screening procedure for the detection of the following alkanolamine antihistamines and their metabolites in urine after acid hydrolysis and acetylation is described: bencyclane, carbinoxamine, chlorbenzoxamine, chlorphenoxamine, clemastine, diphenhydramine, diphenylpyraline, doxylamine, mecloxamine, medrylamine, orphenadrine and phenyltoloxamine. The acetylated extract was analysed by computerized gas chromatography-mass spectrometry. An on-line computer allows rapid detection using ion chromatography with the ions m/z 58, 139, 165, 167, 179, 182, 218 and 260. The identity of positive signals in the reconstructed ion chromatograms was confirmed by a comparison of the stored full mass spectra with the reference spectra. Possible interferences with related compounds that yield the same hydrolysis products or metabolites are discussed. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (OV-101) are documented. The procedure presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs. PMID- 2902104 TI - High-performance liquid chromatographic analysis of neurotransmitter amino acids in brain. AB - Rapid and selective determination of neurotransmitter amino acids in rat and human brain is accomplished by pre-column derivatization with o-phthaldehyde-3 mercaptopropionic acid, reversed-phase high-performance liquid chromatographic separation, and fluorimetric detection. Aspartate, taurine, glutamate, and glycine are determined in less than 12 min with intra- and inter-assay precisions of 2.1-9.5% and 4.2-9.2%, respectively. gamma-Aminobutyric acid is determined in less than 8 min with intra- and inter-assay precisions of 1.6 and 11.7%, respectively. Both assays utilize internal standards and require a minimum of sample preparation. PMID- 2902105 TI - Single-step purification of two hyperglycaemic neurohormones from the sinus gland of Procambarus bouvieri. Comparative peptide mapping by means of high-performance liquid chromatography. AB - A crude aqueous extract from 2000 sinus glands of the Mexican crayfish Procambarus bouvieri (Ortmann) was fractionated on a muBondapak-Phenyl column. Two isoforms of the crustacean hyperglycaemic hormone, designated CHH-B and CHH-C in order of elution, were isolated in pure form. Their biochemical characterization showed a remarkable degree of homology. A tryptic digest of each isohormone was fractionated on an Ultrasphere-ODS column. Only one tryptic peptide in CHH-C was eluted later than its homologous peptide in CHH-B. On acid hydrolysis both tryptic peptides had the same composition but, as they contain Asp and Glu, we suspect that the difference residues in a double reciprocal amidation-deamidation of two acidic residues. PMID- 2902106 TI - Detection of nephropathia epidemica (Puumala virus)-specific immunoglobulin M by enzyme-linked immunosorbent assay. AB - Nephropathia epidemica (NE), a less severe form of hemorrhagic fever with renal syndrome, is caused by Puumala virus (PUU). This communication reports the development of a mu-capture enzyme-linked immunosorbent assay (ELISA) for detection of specific immunoglobulin M (IgM) antibodies to PUU virus in human sera. Acute- and early-convalescent-phase sera (collected 1 to 41 days after disease onset) from 29 Swedish patients with clinical NE were tested for PUU virus-specific IgG and IgM antibodies by the indirect immunofluorescence test and ELISA, respectively. Late-convalescent-phase serum was also collected from 18 of these patients 3 to 24 months postinfection and assayed. The IgM ELISA values were strongly positive in sera collected during the first 2 months; at 3 to 9 months, they were negative or in the lower range of significance, and at 24 months all sera were negative. Paired sera from NE patients often fail to show seroconversion or a significant titer rise when tested by indirect immunofluorescence. Since all acute- and early-convalescent-phase sera were positive by IgM ELISA, this test could become an important tool for early diagnosis of acute human NE infections. PMID- 2902108 TI - Epidermodysplasia verruciformis and cell-mediated immunity. PMID- 2902107 TI - Kappa/lambda immunoglobulin distribution in Graves' thyroid-stimulating antibodies. Simultaneous analysis of C lambda gene polymorphisms. AB - From patients with untreated Graves' disease 11 sera showing high cAMP release in the FRTL-5 cell assay were studied for relative proportions of kappa or lambda Ig molecules showing cAMP releasing activity. Immunoabsorption of gamma-globulins was performed using monoclonal murine anti-kappa or anti-lambda antibodies linked to cyanogen bromide-activated sepharose. Specific kappa- or lambda-adsorbed fractions were also eluted from immunoabsorbents using chaotrophic thiocyanate buffers and equilibrated with pH 7.4 low salt buffer by dialysis. Immunoabsorption and elution experiments showed that five Graves' sera contained predominant cAMP-releasing activity within lambda Ig fractions, whereas two Graves' sera showed predominant cAMP-releasing activity in kappa Ig fractions. Four sera showed cAMP release approximately equally divided between kappa and lambda Ig both after immunoabsorption and specific anti-kappa or anti-lambda eluates were studied. C lambda genotypes were examined by Southern blotting and restriction fragment length polymorphism analysis of Eco RI-digested genomic DNA from 158 patients with Graves' disease in parallel with 112 normal controls and 29 patients with autoimmune hypothyroidism. Notable shifts in proportions of 8/8 and 18/18 genotypes were present when Graves' patients were compared with normal controls. Allelic frequencies and ratios of genotype 8 to 18 were significantly different (P less than 0.05) when Graves' patients were compared either to normal controls or to patients with autoimmune hypothyroidism. PMID- 2902109 TI - Dentofacial trauma in children. AB - Most of the literature on dental injury pertains to the classification, incidence, prevalence, and treatment of fractured teeth. A major finding here is that the five leading causes of dentofacial injuries, regardless of severity, were falls, being struck by an object, bicycle accidents, assaults, and motor vehicle accidents. PMID- 2902110 TI - Dental emergencies presenting to a children's hospital. AB - Most of the 222 dental patients with emergency situations, observed during the period described, had injuries involving the eight incisor teeth (86.1 percent). Patients or their parents facing these situations are often referred to the hospital emergency room, especially those that provide dental services. PMID- 2902111 TI - The use of whole-cell DNA probes for the identification of Bacteroides intermedius isolates in a dot blot assay. AB - Bacteroides intermedius includes two distinct groups of organisms that are phenotypically indistinguishable by conventional methods. These two groups are represented by the type strain of the species ATCC 25611T (B. intermedius type I) and by ATCC 33563 (B. intermedius type II). Members of each group can be distinguished from each other by analysis of the cellular protein composition by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and by DNA-DNA homology studies, because they share less than 40% homology. The purpose of this study was to prepare specific DNA probes for the two groups of Bacteroides intermedius and to test them against field isolates. Whole-cell DNA probes were prepared from B. intermedius types I and II and tested against 253 field strains of Bacteroides which had been identified by conventional phenotypic tests as B. intermedius. Of these, 170 (67%) hybridized with the B. intermedius type I DNA probe, 28 (11%) with the type II, and 23 (9%) failed to react with the B. intermedius probes but did hybridize with either B. melaninogenicus, B. loescheii, or B. corporis whole cell DNA probes. The 32 (13%) remaining isolates failed to hybridize with any of the five Bacteroides probes or with probes to B. asaccharolyticus, B. buccae, B. buccalis, B. denticola, B. gingivalis, B. oralis, or B. oris. These data demonstrate the usefulness of whole-cell DNA probes for the identification of phenotypically similar or identical field isolates. PMID- 2902112 TI - The BamHI restriction fragment length polymorphism detected in the c-Ha-ras locus of human skin tumors. PMID- 2902113 TI - The use of antihistamines in patients with asthma. American Academy of Allergy and Immunology. PMID- 2902114 TI - Effect of levocabastine, a new H1 antagonist, in a conjunctival provocation test with allergens. AB - Levocabastine is a new, highly potent, and specific H1 antagonist. The effects of this drug, administered topically, were evaluated in a conjunctival provocation test (CPT) with allergens. CPT was performed by the instillation of one drop of allergen at increasing concentrations in the inferior conjunctival sac of each eye, alternatively, and stopped when both itching and redness of the conjunctiva were present. The concentration of allergen at this step was considered as the reaction threshold. Eleven patients, allergic to grass pollen, underwent, in winter, a first CPT without pretreatment (screening test); the CPT was then repeated twice after a 24-hour treatment, once, with a placebo, and once, with levocabastine (one drop twice a day, 0.5 mg/ml), administered in a double-blind fashion and in random order. The minimal interval between the two tests was 1 week. There was no significant difference between the thresholds determined in the two CPTs performed without medication (screening test and placebo), whereas the threshold was significantly increased (p less than 0.001) after pretreatment with levocabastine. Individually, the threshold increased in 10/11 patients (p less than 0.01). Levocabastine prevented both redness and itching. A late allergic reaction was observed by the patient in 6/11 CPTs performed after placebo treatment and 8/11 after levocabastine treatment. We conclude that, in this model of allergic conjunctivitis, levocabastine increased the conjunctival tolerance to an allergen. Further studies should help to determine the true place of this H1 antagonist in the treatment of allergic conjunctivitis. PMID- 2902115 TI - Meprobamate use in the elderly. A report from the Dunedin program. AB - Meprobamate use was studied in an ambulatory elderly population in Dunedin, Florida. All participants taking this medication were mailed a questionnaire concerning their pattern of use. From 2,278 subjects, 30 (1.3%) reported the use of this drug. The average age of participants using this drug was 81.3 years. Five participants began using the drug over 27 years ago and over one-half of the respondents reported using the drug on a regular basis for over 10 years. With this type of history of meprobamate use, one might expect to encounter a large number of patients in the future who, in a similar manner, have been using benzodiazepines for many decades. PMID- 2902116 TI - Oxmetidine (H2 receptor antagonist) induced cytotoxicity in isolated rat hepatocytes. AB - Oxmetidine, a new and more potent analogue of the H2 receptor antagonist, cimetidine, was recently withdrawn from clinical trials because of associated hepatotoxicity. We investigated the potential hepatotoxicity of the drug in vitro and in vivo in the rat. In addition, we investigated, in in vitro experiments, the potential hepatoxicity of other gastric acid inhibitory drugs (cimetidine, ranitidine, omeprazole and nolinium bromide). In in vitro experiments, oxmetidine, at various concentrations, was added to isolated hepatocyte incubations and cytotoxicity was assayed by trypan blue exclusion. In in vivo experiments, oxmetidine was administered both i.p. and orally, and hepatotoxicity was assessed by serum biochemical measures (transaminases, alkaline phosphatase, 5' nucleotidase, gamma glutamyl transpeptidase) and liver histopathology. In the in vitro studies, the addition of oxmetidine to the hepatocyte incubations was associated with significant (P less than 0.001) dose and time dependent cytotoxicity. However, the in vivo experiments revealed no significant changes in serum biochemistry and no significant alterations in liver histopathology up to 72 h following the administration three different dosages of oxmetidine. Of the other gastric acid inhibitory drugs, only nolinium bromide was associated with significant (P less than 0.001) in vitro cytotoxicity. Our in vitro observations establish that oxmetidine is cytotoxic to isolated rat hepatocytes and suggest that nolinium bromide be further evaluated for potential hepatotoxicity. PMID- 2902117 TI - Activation of gastric afferent fibers increases coronary arterial resistance in anesthetized dogs. AB - Stimulation of chemically sensitive receptors in the stomach with capsaicin is known to reflexly increase heart rate, arterial pressure, left ventricular contractility, and systemic vascular resistance. What is not known, however, is if activating these gastric afferents can also evoke reflex changes in coronary arterial resistance. Therefore, in 24 chloralose-anesthetized dogs, we used a Gregg cannula and a constant flow preparation to assess left circumflex coronary arterial (LCCA) resistance while stimulating chemically sensitive gastric receptors with capsaicin. Capsaicin (60 micrograms), applied topically to the serosal surface of the stomach, produced significant (P less than 0.05) increases in heart rate (8 +/- 2 bpm), mean arterial pressure (22 +/- 1 mm Hg), LCCA pressure (7 +/- 1 mm Hg), and LCCA resistance (0.30 +/- 0.04 mm Hg/ml/min). These responses were still present after bilateral thoracic vagotomy, but were eliminated by bilateral thoracic splanchnicotomy. alpha-adrenergic blockade eliminated and beta-adrenergic blockade enhanced the increases in LCCA pressure and resistance that were evoked by capsaicin. Thus, stimulating chemically sensitive receptors in the stomach can reflexly increase coronary arterial resistance by alpha-adrenergic vasoconstriction. The possibility exists, therefore, that physiological or pathological events which activate gastric afferents can affect reflexly the coronary circulation. PMID- 2902118 TI - Effects of activating spinal alpha-adrenoreceptors on sympathetic nerve activity in the rat. AB - The effects of several alpha-adrenoreceptor agonists and antagonists administered intrathecally at T10 level on renal sympathetic nerve activity (RSNA) were examined, in chloralose-urethane anaesthetised rats. Intrathecal noradrenaline (NA, 0.5-500 micrograms) produced one of 3 responses depending on dose, an inhibition of RSNA at low doses, an excitation of RSNA at high doses, or a biphasic effect. Intrathecal adrenaline (5-200 micrograms) was inhibitory in the main but some doses elicited poorly repeatable brief excitation followed by prolonged inhibition. Intrathecal methoxamine (ME; 2.5 ng-25 micrograms) caused a dose-dependent increase in RSNA (mean maximum response 27 +/- 0.5%). The excitatory effects of NA and ME were blocked (72% +/- 12%) by pretreatment with intrathecal prazosin (PRA, 20-200 ng) but not by yohimbine (YOH, 200 ng). Intrathecal guanabenz (GUA 3-15 micrograms) caused a dose-dependent inhibitory effect on RSNA (mean maximum 32% +/- 5%). The inhibitory effects of NA, adrenaline and GUA were blocked by pretreatment with intrathecal YOH (200 ng-2 micrograms). Intrathecal PRA (200 ng) had no effect on the inhibitory effects of NA and GUA. Intravenous administration of each of the adrenoreceptor agonists (apart from adrenaline), at similar doses to those given intrathecally, in most cases had no significant effect on RSNA; in a few cases the opposite effects to those produced by intrathecal administration were seen. PMID- 2902119 TI - Somatostatin-like immunoreactivity in a subpopulation of nerve terminals in frog sympathetic ganglia. AB - A somatostatin-like substance was observed specifically in a subset of B-type nerve terminals in frog paravertebral ganglia. The middle ganglia (4th and 5th) of the sympathetic chain contained the highest proportions of somatostatin positive terminals, with decreasing proportions in more caudal or rostral ganglia. Intracellular recordings from the 6th ganglion demonstrated that it contained both B and C neurons. Although prolonged depolarizing potentials were observed in B and C neurons after bursts of stimuli in C-type preganglionic axons, no slow potentials were observed after stimulating somatostatin-positive B type axons. In addition, no effects of exogenously applied somatostatin were observed on the membrane potentials of B neurons. The present results are compared to a growing list of autonomic systems where peptidergic transmitters appear to have only subtle or no acute electrical consequences on postsynaptic neurons. PMID- 2902120 TI - Tonic descending inhibition of the spinal cardio-sympathetic reflex in the cat. AB - Electrical stimulation of the left inferior cardiac nerve elicited a two component reflex potential (spinal and supraspinal reflexes) in the ipsilateral white ramus T3 from which recordings were made in chloralose-anaesthetised cats. Reversible interruption of all spinal pathways achieved by cooling the spinal cord at C2/C3 produced an enhancement of the spinal reflex and abolished the supraspinal reflex, the latter usually being the more prominent reflex potential prior to spinal cord block. The spinal cord block-induced increase in the amplitude of the spinal reflex was, however, less than the increase observed during stimulation of the somatic intercostal nerve T4. Recordings of the afferent volley following cardiac nerve stimulation and analysis of the stimulus reflex response relationship in neuraxis-blocked cats indicated that the spinal reflex as determined here was activated by A delta afferent fibres. However, if stimulus strength was raised above C-fibre threshold, spinal cord block revealed in addition a late spinal reflex response. In some cases, the appearance of this late potential was accompanied by a secondary decline of the earlier spinal reflex potential, possibly indicating C-fibre-mediated afferent inhibition. Neither baroreceptor activation nor denervation had any effect on spinal reflex amplitudes. Pharmacologically, clonidine given i.v. to cats with a blocked neuraxis reduced the spinal reflex amplitudes to pre-block values, an action which could be antagonised by the subsequent administration of the alpha 2 adrenoceptor antagonist rauwolscine. When given to non-pretreated cats with intact neuraxis, however, neither rauwolscine nor its analog yohimbine were capable of inducing a persistent release from tonic inhibition. The results suggest that both purely visceral and somato-visceral reflexes are subject to tonic descending inhibition, but they do not support the hypothesis that a catecholamine is the responsible transmitter mediating this inhibition. PMID- 2902121 TI - Influence of selective parasympathectomy of the A-V nodal region on atrioventricular conduction in conscious dogs. AB - The maximum atrial paced rate with 1:1 atrioventricular conduction (Rmax) was compared before and after selective parasympathectomy of the atrioventricular nodal region (AVNR). Each animal was instrumented with right atrial and right ventricular bipolar electrodes. Rmax was determined (1) under quietly resting, control conditions, (2) following beta-adrenergic blockade, (3) following muscarinic blockade, and (4) following combined beta-adrenergic and muscarinic blockade. During a second surgical procedure approximately two weeks later, parasympathectomy was achieved by dissection and topical application of phenol to the fat pad and underlying epicardium at the inferior left atrial junction with the inferior vena cava; completeness of AVNR parasympathectomy was tested at surgery by supramaximal stimulation of right and left cervical vagi, with and without rapid atrial pacing. AVNR sympathetic innervation remained intact. All studies were conducted while the animals were conscious and quietly resting. Before parasympathectomy, Rmax under control conditions averaged 136 +/- b4 beats per minute (bpm). Following beta-blockade, Rmax was 126 +/- 5 bpm; while with muscarinic blockade, Rmax averaged 373 +/- 4 bpm (P less than 0.001, with control). With combined beta- and muscarinic blockade, Rmax was 300 +/- 14. After AVNR parasympathectomy, although the resting heart rate was unchanged, the Rmax under control conditions was 342 +/- 10 bpm. beta-Blockade reduced this significantly (P less than 0.001) to 278 +/- 15 bpm. With muscarinic blockade, Rmax averaged 346 +/- 11 bpm, which was not different from the control Rmax after AVNR parasympathectomy. Combined beta- and muscarinic blockade produced an Rmax of 280 +/- 14 bpm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902122 TI - Evidence for a sympathoexcitatory pathway from the nucleus tractus solitarii to the ventrolateral medullary pressor area. AB - The role of the ventrolateral medullary pressor (VLPA) and depressor (VLDA) areas in mediating cardiovascular responses evoked from the nucleus tractus solitarius (NTS) was investigated. Male Wistar rats, anesthetized with pentobarbital or urethane, were artificially ventilated and blood pressure (BP) and heart rate (HR) were monitored. The VLPA, VLDA, and the NTS were identified bilaterally with microinjections of L-glutamate. Unilateral microinjections of muscimol or lidocaine into the VLPA or the VLDA blocked the decrease in BP produced by microinjections of L-glutamate (1.77 nmol) into the NTS. These findings indicate that both areas are essential for mediating depressor responses elicited from the NTS. When neuronal activity in the VLDA was depressed unilaterally (leaving the ipsilateral VLPA intact), with the microinjection of muscimol or lidocaine, microinjection of a larger dose (5.0 nmol) of L-glutamate into the ipsilateral NTS elicited a pressor response. This response was blocked by depressing neuronal activity in the ipsilateral VLPA by microinjection of muscimol into this site. This pressor response evoked from the NTS was not due to non-specific effects of L-glutamate since repeated microinjections of L-glutamate (5.0 nmol/site) into the NTS consistently produced decreases in BP and HR. The stimulation of the contralateral NTS by glutamate continued to elicit the usual decreases in BP and HR. Microinjections of either dose (1.77 or 5 nmol) of L-glutamate into the areas adjacent to the NTS (e.g. 1.0 mm rostral or lateral to the NTS, the gracile or cuneate nuclei and area postrema) failed to evoke any cardiovascular responses indicating that the responses were mediated by neurons localized within the intermediate one-third of the NTS. These results indicate that: (1) the depressor responses elicited from the NTS involve the pathways from the NTS to the VLDA and VLDA to VLPA and (2) there may be a pathway from the NTS to the VLPA which is sympathoexcitatory and is unmasked when neuronal activity in the VLDA is depressed. PMID- 2902124 TI - Intravenous immunoglobulin therapy in serious infections. PMID- 2902125 TI - Clinical safety of intravenous immune globulin and freedom from transmission of viral disease. AB - Although rare, side-effects have been associated with the administration of iv immune globulins (IVIG). While the clinical presentation may be similar, several different mechanisms account for these adverse reactions. There are those effects in the hypogammaglobulinaemic patient which are probably due to antigen-antibody interaction (so-called inflammatory reactions), those due to spontaneous activation of the complement system (possibly caused by IgG aggregates), those due to true hypersensitivity (for example, hypersensitivity to IgA), and those due to possible contaminants or even stabilizers or preservatives which might have been used. The incidence and nature of clinical side-effects seen in 37 patients who were treated with a native IVIG is shown. In addition, data are provided which support the absence of transmission of human immune deficiency virus in idiopathic thrombocytopenia (ITP) patients, and the agents of non-A, non B hepatitis in 41 immune-deficient patients having periods of follow-up ranging up to 18 months. Finally, evidence of the inactivation of human immunodeficiency virus during the manufacturing procedure is provided. PMID- 2902126 TI - Acute graft-vs.-host disease and interstitial pneumonitis interrelated problems following allogeneic bone marrow transplantation: effects of intravenous immune globulin and other interventions. PMID- 2902127 TI - The effect of processing methods on intravenous immune globulin preparations. AB - In this comparative study we investigated five commercially available immunoglobulin preparations manufactured by various processing methods. Two enzyme-modified preparations and one chemically modified preparation demonstrated appreciable variation in molecular weight species when compared with native preparations utilizing gentle processing conditions. One native preparation, processed with DEAE Sephadex, was low in IgG4 subclass, while the enzymic and chemical processing methods provided products demonstrating substantial variation in subclass distribution. The other native preparation, formulated at low pH, demonstrated particularly low turbidity values, indicating greater IgG stability at pH 4.25 than at pH 7.0. Certain antibody levels were seen to be greatly reduced in the modified preparations. These differences are discussed with reference to effects of the processing conditions employed. PMID- 2902128 TI - The treatment of human immunodeficiency virus infected patients with intravenous immunoglobulin. AB - The main immunological abnormality described in patients with the acquired immunodeficiency syndrome (AIDS) is the deficiency in cellular immunity. However, there is increasing evidence of a deficiency of specific antibody synthesis in both symptomatic human immunodeficiency virus (HIV)-infected children and in some HIV-infected adults who are symptomatic or who suffer from AIDS. In uncontrolled studies as well as those using historical controls, iv immunoglobulin (IVIG) has been shown to benefit HIV-infected children with recurrent infection when used in doses similar to those needed to treat patients with primary hypogammaglobulinaemia. Preliminary data in adults show that IVIG therapy reduces bacterial infection but the optimal treatment schedules remain to be defined. In addition, high-dose IVIG treatment (1-2 g kg-1) produces increased platelet counts in patients with life-threatening bleeding due to idiopathic thrombocytopenic purpura associated with HIV infection. Unlike other therapies, IVIG has the advantage of lacking immunosuppressive and other serious adverse effects. In HIV-infected patients, IgG therapy may limit the antigenic stimulation caused by intercurrent infection, and studies of asymptomatic patients are needed in order to investigate whether this might slow the progression to AIDS. Neutralizing antibody against HIV has been demonstrated in HIV-infected patients. Although the significance of this finding is not clear, a specific antibody preparation against HIV may be of value either to prevent HIV infection after initial exposure to the virus or to slow the progression of HIV related disease. Major difficulties will be encountered in producing a specific, effective, neutralizing anti-HIV immunoglobulin preparation, since it is not known which HIV antigens elicit protective immunity. PMID- 2902123 TI - Luteinizing hormone-releasing hormone and its analogues: a review of biological properties and clinical uses. PMID- 2902129 TI - Intravenous immunoglobulin (IVIG) for gram-negative infection--a critical review. PMID- 2902130 TI - Recent experience with Pseudomonas aeruginosa immune globulin for the treatment of experimental pneumonia. AB - A guinea-pig model of experimental Pseudomonas aeruginosa pneumonia was used to determine what factors affect the efficacy of passive immune therapy with a hyperimmune P. aeruginosa globulin (PA-IGIV). Animals treated 2 h after infection with a single iv infusion of PA-IGIV, 500 mg kg-1, demonstrated 33% survival. Lower dosages were less effective and there were no survivors among albumin treated controls. Treatment with PA-IGIV was effective if given 2 or 8 h after infection but not if delayed until 24 h after infection. Animals rendered neutropenic with cyclophosphamide did not survive if treated with PA-IGIV alone. However, when PA-IGIV was added to tobramycin treatment, a significant increase in survival occurred (86%) as compared with that observed with tobramycin alone (43%) (P less than 0.05). We conclude that PA-IGIV may offer a useful therapeutic option in management of P. aeruginosa pneumonia. PMID- 2902131 TI - Hyperimmuneglobulin for cytomegalovirus prophylaxis following heart transplantation. AB - Cytomegalovirus continues to be an important cause of morbidity and mortality following organ transplantation. In a series of 75 heart transplant patients, we have compared two protocols for prophylactic administration of CMV hyperimmuneglobulin. The first group of patients received immunoglobulin on the operative and on the tenth postoperative days. The second group of patients received immunoglobulins on the operative day, and repeatedly with each period of increased immunosuppression. With repeated doses of immunoglobulin prophylaxis, the incidence of CMV reactivation and the clinical severity of CMV infection were both significantly reduced. A reduction in the incidence of CMV infection in recipients who were seronegative preoperatively was also observed. (5/8 vs. 7/25 patients; P = 0.06). We conclude that repeated administration of specific hyperimmuneglobulin with each period of increased immunosuppression following heart transplantation has a beneficial effect on both CMV reactivation and infection. PMID- 2902132 TI - Treatment of human immunodeficiency virus antibody positive children with intravenous immunoglobulin. AB - Five human immunodeficiency virus (HIV) antibody positive children developed recurrent infections requiring multiple hospital admissions. These comprised mainly upper respiratory tract infections, otitis media, pneumonia and diarrhoea, and there was failure to thrive despite adequate antibiotic therapy. They were commenced on iv immunoglobulin (IVIG) therapy and are now relatively free of serious infections and are gaining weight. This therapy was associated with a major reduction in the hospitalization required. In HIV antibody positive children the onset of serious infections, particularly with encapsulated gram positive organisms, should be taken as an indication for the commencement of regular iv infusions of immunoglobulin. PMID- 2902133 TI - Synthesis of catecholamines in the hypothalamus and brainstem in one-kidney, one clip and two-kidney, one clip hypertension in rabbits. AB - In order to examine the role of central catecholaminergic neurons in hypertension, the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamines, was studied in the hypothalamus, midbrain, pons-upper medulla, mid-medulla and lower medulla of one-kidney, one clip (1 K,1C) and two-kidney, one clip (2-K,1C) hypertensive rabbits and their respective operated controls (1-K,1 Cc and 2-K,1 Cc). Comparing the 1-K,1 C group to the 1 K, 1 Cc group, the activity of TH was increased by 79% in the hypothalamus (P less than 0.02), 37% in the mid-medulla region (P less than 0.02) and was unchanged in the midbrain, pons-upper medulla and the lower medulla. Comparing the 2-K,1 C group to the 2-K,1 Cc group, the activity of TH was increased by 89% in the mid-medulla (P less than 0.01), decreased by 36% in the pons-upper medulla (P less than 0.01) and unchanged in the hypothalamus, midbrain and lower medulla. These results indicate that similarities and differences exist in the contribution of central catecholaminergic neurons to the pathophysiology of 1-K,1 C and 2-K,1 C hypertension in rabbits. PMID- 2902134 TI - Beta 1- and beta 2-adrenoceptor-mediated relaxation responses in peripheral arteries from spontaneously hypertensive rats at pre-hypertensive and early hypertensive stages. AB - Beta-adrenoceptor-mediated relaxation of isolated arteries from spontaneously hypertensive rats (SHR) was studied. The relaxation responses of the femoral arteries of pre-hypertensive SHR (PHSHR) to isoprenaline (ISO) and dibutyryl cyclic AMP were less than those of the age-matched tissues of rats of the Wistar Kyoto strain (WKY). The responses of the mesenteric arteries of PHSHR to ISO and noradrenaline (NA) but not fenoterol (FEN) and forskolin were diminished when compared to those from the WKY tissues. The diminished relaxation response to ISO was observed in the SHR arteries with and without endothelial cells as compared to similar arteries from WKY. Relative potency ratios of ISO:FEN:NA and the Schild plot data for atenolol and butoxamine suggested that there were only beta 1-adrenoceptors and predominantly beta 2-adrenoceptors mediating relaxation in the femoral and mesenteric arteries, respectively. There was no difference in beta-adrenoceptor subtypes between the SHR and WKY arteries. The evidence in this study suggests that beta 1-adrenoceptor-mediated relaxation was diminished in the femoral and mesenteric arteries of PHSHR. PMID- 2902135 TI - Plasma renin activity in phaeochromocytoma: effects of beta-blockade and converting enzyme inhibition. AB - We measured plasma renin activity and plasma catecholamines in 26 untreated patients with phaeochromocytoma, 18 untreated patients with primary hypertension, and 10 normal control volunteers. Plasma renin activity measured in patients in the supine position, standing position and after walking for 1 h was higher in the subjects with phaeochromocytoma than in those with primary hypertension or in the volunteers (F = 9, P less than 0.001). In all three situations, renin activity was closely correlated with noradrenaline levels in the phaeochromocytoma patients (r = 0.545, r = 0.600, and r = 0.739; P less than 0.01) but not in the subjects with primary hypertension or in the volunteers. The cardioselective beta-blocker acebutolol reduced heart rate, mean blood pressure and renin activity by averages of 20, 12 and 89% respectively in the seven phaeochromocytoma patients given the drug. Captopril decreased mean blood pressure by 19% and raised renin activity by 293% in the nine phaeochromocytoma patients tested. These findings show that in phaeochromocytoma, hypertension is accompanied by high renin levels and that renin release is stimulated in response to noradrenaline overflow. The hypotension observed in response to beta-blockade and captopril provides indirect support for the possibility that renin-dependent mechanisms are involved in the hypertension of phaeochromocytoma. PMID- 2902136 TI - Thy-1+ epidermal cells in nude mice are distinct from their counterparts in thymus-bearing mice. A study of morphology, function, and T cell receptor expression. AB - We have evaluated the morphology, function, and TCR mRNA and DNA profiles of Thy 1+ epidermal cells (EC) derived from athymic (nude) mice. Based on these criteria we demonstrate that Thy-1+ EC in nude mice are predominantly round and angular and located in follicular epithelium, as compared to predominantly dendritic, interfollicular Thy-1+ EC found in normal CBA or BALB/c mice. Functionally, Thy 1+ EC from normal mice proliferate and elaborate IL-2 in response to stimulation by Con A; by contrast, nude Thy-1+ EC fail to proliferate or secrete IL-2 in response to Con A. Nude Thy-1+ EC proliferate markedly in response to low-dose IL 2 alone; Thy-1+ EC from normal mice give only modest proliferative responses to IL-2. Both populations of cells proliferate and elaborate IL-2 in response to PMA and calcium ionophore. Short-term cultured Thy-1+ EC from nude mice resemble Thy 1+ EC from normal animals in that they express no detectable functional TCR-alpha and beta-RNA. Normal Thy-1+ EC express abundant levels of functional RNA for TCR gamma and delta-chains and for the CD3 delta-chain, whereas nude Thy-1+ EC produce no detectable TCR-delta and no CD3 delta-RNA and only truncated, presumably germ-line TCR-gamma transcripts, as suggested by lack of hybridization with gamma-V region probes and by lack of detectable rearrangements in the gamma genes. These phenotypic, functional, and genotypic characteristics of Thy-1+ EC from nude mice suggest that these cells are at a very early stage of T cell differentiation. PMID- 2902137 TI - Development of self-tolerance in normal mice. Appearance of suppressor cells that maintain adult self-tolerance follows the neonatal autoantibody response. AB - T cell populations from BALB/c mice at different ages were analyzed to determine when in development Ts cells specific for the anti-mouse RBC (MRBC) autoantibody response become activated. Previous studies have shown that adult CD8+ T cells actively suppress this autoimmune response and adult spleen cells depleted of CD8+ cells can generate an anti-MRBC response in culture with MRBC. The present results demonstrate that T cells from mice less than 1 wk of age do not suppress the in vitro anti-MRBC response of adult spleen cell populations depleted of CD8+ Ts cells. By 2 wk of age Ts cells are detectable in this anti-self response and reach adult levels by 3 wk of age. Non-specific "natural suppressor" cells normally present in neonatal spleen cell populations are unable to suppress this autoantibody response, although they are active in suppressing anti-SRBC responses in the same cultures. Before the appearance of Ts cells active in the anti-MRBC response, neonatal spleen cell populations can generate anti-MRBC antibody-forming cells, both spontaneously in vivo and in vitro. The in vitro anti-MRBC response of neonatal spleen cells was shown to be Ag driven and Ag specific. The ability of unfractionated spleen cells to generate this response in vitro declines with age and is relatively low by 3 wk. This decline in responsiveness occurs simultaneously with the appearance of suppression specific for the anti-MRBC response, suggesting that the two events may be causally related. PMID- 2902139 TI - Characterization of lymphoid tumors induced by a recombinant murine retrovirus carrying the avian v-myc oncogene. Identification of novel (B-lymphoid) tumors in the thymus. AB - Lymphoid tumors induced by a recombinant murine retrovirus carrying the v-myc oncogene of avian MC29 virus were characterized. The Moloney murine leukemia virus myc oncogene (M-MuLV (myc], carried by an amphotropic MuLV helper, induced tumors in NIH Swiss and NFS/N mice after a relatively long latency (8 to 24 wk). Tumor masses appeared in the thymus, spleen, and lymph nodes. Flow cytometry of the tumor cells indicated that approximately 50% were positive for Thy 1.2. Most of these tumors also expressed one or more other cell surface markers of thymocytes and mature T cells (CD4, CD8). Southern blot hybridization revealed genomic rearrangements for the TCR beta genes. The TCR beta analysis suggested that the M-MuLV(myc)-induced Thy 1.2+ tumors were derived from somewhat less mature cells than tumors induced by M-MuLV, which is a classical non-acute retrovirus lacking an oncogene. The remainder of the M-MuLV(myc)-induced tumors were Thy 1.2-, but they were positive for Ly-5 (B220) and also for MAC-2. The Thy 1.2- tumors were characteristically located in the thymus. However, they were negative for TCR beta gene rearrangements. Some, but not all, of the Thy 1.2- tumors contained rearrangements for Ig genes. Additionally, they typically expressed mRNA specific for B but not for T cells. Thus, these thymic tumors had characteristics of the B cell lineage. Tumor transplantation experiments demonstrated that the Thy 1.2- tumor cells could reestablish in the thymus and spleen of irradiated hosts, and low level expression of the Thy 1 molecule was observed in the thymus but not the spleen on the first passage. After serial passage, one Thy 1- tumor altered its cell surface phenotype to Thy 1low B220-. PMID- 2902138 TI - Receptor-like nature of class I HLA: endocytosis via coated pits. AB - The present investigations show that class I HLA are internalized by macrophage/monocyte type cells. Anti-class I antibody-binding assays show that about 30% of class I Ag present on cell surface are endocytosed within 1 h. Electronmicroscopic investigations reveal that, like other well established receptor molecules, internalization of HLA is mediated by coated pits and coated vesicles. The endocytosed Ag are transferred from endosomes to trans-Golgi reticulum and trans-Golgi cisternae, suggesting recycling of these Ag back to the cell surface. In the presence of phorbol ester tetradecanoyl phorbol acetate, there is a modest increase in the rate of internalization. These results are consistent with the hypothesis that class I Ag on monocytes/macrophages behave like receptor molecules. Malignant transformation of monocytic cells apparently causes the loss of this property of class I Ag. PMID- 2902140 TI - A role of HLA-DQ molecules of stimulator-adherent cells in the regulation of human autologous mixed lymphocyte reaction. AB - In this study, we have found that treatment of stimulator autologous adherent cells with anti-HLA-DQ mAb resulted in markedly enhanced proliferative response of T cells in human autologous mixed lymphocyte reaction system wherein T cells were cultured with autologous adherent cells at near ratio of adherent cells to T cells in peripheral blood, in which T cells minimally proliferate. However, treatment of stimulator-adherent cells with anti-HLA class I, anti-DR and anti-DP mAb had no effect on the proliferative response of T cells under the condition. It was further observed that CD4-enriched cells could significantly proliferate in the presence of autologous adherent cells either untreated or treated with anti-DQ mAb, although treatment of adherent cells with anti-DR mAb blocked proliferative response of CD4-enriched cells. Moreover, the proliferative response of CD4-enriched cells was suppressed by addition of CD8-enriched cells in the presence of untreated adherent cells, whereas the proliferative response of CD4-enriched cells could not be suppressed by CD8-enriched cells when the adherent cells in the culture were treated with anti-DQ mAb. These observations suggest that CD8 T cells are required for suppression of proliferative response of CD4 T cells to HLA-DR molecules on autologous stimulator-adherent cells, and that HLA-DQ molecules on the surface of adherent cells play an important role in the induction of suppression by CD8 T cells. PMID- 2902141 TI - Modulation of experimental allergic encephalomyelitis with anti-T suppressor factor antibodies. AB - mAb reactive with T suppressor factors (TsF) were used to alter the course of myelin basic protein-induced experimental allergic encephalomyelitis in (SJL/J x PL/J)F1 mice. In vivo administration of mAb 14-12, reactive with effector TsF, exacerbated the clinical expression of encephalomyelitis as evidenced by prolonged periods of total limb paralysis in affected animals. This aggravation of disease signs is probably related to the inhibition of effector Ts function by mAb 14-12 thus allowing T cell autoreactivity to proceed unchecked. Disease course was influenced more favorably by i.v. administration of mAb 14-30 reactive with a subset of inducer TsF. Ten days of treatment with this mAb resulted in a reduction in the incidence and severity of disease, noted as the development of minimal limb weakness but no paralysis in the majority of affected animals. Adoptive transfer experiments revealed the presence of Ag-specific Ts in mAb 14 30-treated mice that inhibited recipient Lyt-1+ responses to myelin basic protein, the immunizing autoantigen. Suppression by transferred Ts was revealed only by treatment of the donor population with anti-Lyt-1.2 plus C, however, indicating a role for contrasuppressor activity in the regulation of autoimmune T cell function. Results are considered relevant to the potential for immunotherapeutic management of multiple sclerosis in man. PMID- 2902142 TI - The selection of effector T cell phenotype by contrasuppression modulates susceptibility to autoimmune injury. AB - The genetic susceptibility to murine alpha TBM disease is a dominant trait that maps to H-2K. In previous studies we have shown that the critical difference between susceptible (SJL) and nonsusceptible (B10.S(8R] mice is the phenotype of the tubular Ag-specific effector T cells (TDTH). In SJL mice, these TDTH are Lyt 2+, whereas in B10.S(8R) mice the TDTH are L3T4+. These phenotypic differences have an important functional correlate: Lyt-2+ TDTH are nephritogenic, whereas L3T4+ TDTH are typically not nephritogenic. Both mouse strains have the potential to differentiate both L3T4+ and Lyt-2+ TDTH. The preferential selection of a single TDTH phenotype in each is the result of differential T cell regulation. In the present studies, we have examined the contribution of suppressor and contrasuppressor T cells in the regulation of TDTH phenotype selection. Our studies show that in both SJL and B10.(8R) mice, after exposure to Ag, a suppressor T cell subpopulation functions to inhibit the nephritogenic Lyt-2+ TDTH. In SJL, but not B10.S(8R) mice, this suppression is counterbalanced by Lyt 2+, Vicia Villosa lectin-adherent T cells. Such contrasuppressor function is mediated through a T cell-derived soluble protein (TcsF), which is Ag-binding and recognized by alpha I-JS antisera. This functional TcsF activity maps, as does susceptibility to disease, to H-2K. In the presence of genetically compatible TcsF, the TDTH phenotype in nonsusceptible mice switches to that of susceptible mice. These Lyt-2+ TDTH from nonsusceptible mice are fully capable of inducing tubulointerstitial nephritis following adoptive transfer. Our studies describe a new role for Tcs cells and augment our understanding of their etiopathogenetic role in autoimmunity. PMID- 2902143 TI - CD4 positive Leu-8 negative helper-inducer T cells predominate in the human intestinal lamina propria. AB - The regulatory function of peripheral blood CD4 T cells correlates with the presence or absence of the membrane glycoprotein recognized by anti-Leu-8 antibody; CD4,Leu8- T cells help Ig synthesis and CD4,Leu-8+ T cells suppress Ig synthesis. In contrast to CD4 T cells from the peripheral blood and organized gut associated lymphoid tissues, intestinal lamina propria CD4 T cells were found to have diminished expression of the Leu-8 Ag. Therefore, studies were performed to determine whether the decreased expression of the Leu-8 Ag on lamina propria CD4 T cells correlates with a difference in the ability of peripheral blood and lamina propria CD4 T cells to regulate PWM-stimulated Ig synthesis. At high T cell to non-T cell ratios, the helper function of lamina propria CD4 T cells was significantly higher than that of peripheral blood CD4 T cells. When CD4 T cells were incubated with anti-Leu-8 antibody, the suppressor function of peripheral blood CD4 T cells was increased, but lamina propria CD4 T cells did not suppress Ig synthesis. No difference was found between the helper function of CD4,Leu-8- T cells and the suppressor function of CD4, Leu-8+ T cells isolated from either the peripheral blood or the lamina propria. Thus, the difference in the regulatory function of CD4 T cells from the peripheral blood and the lamina propria is due to the quantitative difference in CD4,Leu-8+ T cells in these sites. Consequently, the intestinal lamina propria is a site enriched in CD4,Leu-8- T cells which predominantly mediate help for Ig synthesis. PMID- 2902144 TI - The IL-4 gene maps to chromosome 11, near the gene encoding IL-3. AB - IL-4/B cell stimulatory factor 1 (IL-4) is a potent mediator of the growth and differentiation of cells of most hemopoietic lineages. IL-4 is one of a number of lymphokines produced by T cells after activation with Ag or mitogen. In order to map the chromosomal location of the IL-4 gene, Chinese hamster-mouse somatic cell hybrids were used in Southern blot analyses with an IL-4 cDNA probe. These results suggested that the IL-4 gene was located on chromosome 11. In contrast, the gene encoding IL-2 was localized to either chromosome 1 or 3. The identification of a strain-specific Bgl II restriction enzyme polymorphism in the IL-4 gene was used to map the IL-4 gene to a position on mouse chromosome 11 within 1 centimorgan of the gene encoding IL-3. PMID- 2902145 TI - Endocytic pathway of recombinant murine tumor necrosis factor in L-929 cells. AB - The fate of TNF after binding to the surface of L-929 cells was followed by using murine rTNF coupled to colloidal gold as a probe. A time-course study using electron microscopy was performed. Our results confirm previous indications obtained from biochemical studies suggesting that TNF is internalized by this cell type. They further directly show that internalization proceeds through the classical receptor-mediated endocytosis pathway, i.e., via clathrin-coated structures and endosomes before accumulation in secondary lysosomes. PMID- 2902146 TI - Effects of somatostatin on acute pancreatitis induced in rats by injection of taurocholate and trypsin into a temporarily closed duodenal loop. AB - The effect of somatostatin on the course and severity of experimental pancreatitis was tested. Acute pancreatitis was induced in 210 Sprague-Dawley rats by injecting a 4.3% sodium taurocholate solution, saturated with trypsin, into a temporarily closed duodenal loop. Immediately after the end of the surgical procedure somatostatin or, alternatively, normal saline were administered as a bolus followed by continuous subcutaneous infusion for 9 h. Ninety rats (30 untreated, 30 saline-treated and 30 somatostatin-treated) were sacrificed 10 h after the induction of pancreatitis to assess the histologic severity of pancreatic lesions, the amount of peritoneal exudate and the circulating levels of amylase. In another 120 rats (40 untreated, 40 saline treated and 40 drug-treated) the mortality rate was evaluated so that the histologic examination of the pancreas followed spontaneous death. In sacrificed animals somatostatin treatment lowered serum amylase levels and definitely improved pancreatic histopathology (edema, leucocyte infiltration and necrosis). The drug prevented the occurrence of severe necrosis in all treated animals. Somatostatin did not affect the mortality rate of pancreatitic rats (70%) although post-mortem histologic examination revealed significantly less pancreatic histopathology in drug-treated rats than in their controls. PMID- 2902147 TI - The effects of epinephrine on islet hormone secretion in the dog. AB - We investigated the direct effects of physiological levels of epinephrine on the basal and arginine-stimulated secretion of insulin, glucagon, and somatostatin from the in situ pancreas in halothane-anaesthetized dogs. An IV infusion of 20 ng/kg/min of epinephrine increased plasma epinephrine levels to 918 +/- 103 pg/ml (P less than 0.001), and increased the baseline pancreatic output of insulin (P less than 0.05), glucagon (P less than 0.05) and somatostatin (P less than 0.05). The acute insulin response (AIR) to 2.5 g of arginine during this infusion of epinephrine was significantly higher (P less than 0.05) than in controls as were the acute glucagon response (AGR) (P less than 0.05) and the acute somatostatin response (ASLIR) (P less than 0.05). Plasma glucose levels increased slightly and transiently during infusion of epinephrine from 99 +/- 2 mg/dl to a maximum of 110 +/- 3 mg/dl (P less than 0.05). An IV infusion of 80 ng/kg/min of epinephrine produced plasma epinephrine levels of 2,948 +/- 281 pg/ml, and increased the baseline pancreatic output of insulin (P less than 0.05) and glucagon (P less than 0.05). In contrast, baseline somatostatin output decreased transiently during this high dose infusion of epinephrine. The AIR and ASLIR to arginine were both significantly lower (P less than 0.05) than those during the infusion of epinephrine at the low dose. The AGR to arginine remained potentiated (P less than 0.05). Plasma glucose levels increased from 99 +/- 3 mg/dl to 119 +/- 4 mg/dl (P less than 0.01). We conclude that the effect of epinephrine on islet hormone secretion is dependent on the plasma level of epinephrine. At stress levels of 900-1000 pg/ml, both insulin and somatostatin secretion are stimulated; only at near pharmacologic, or extreme stress levels, does epinephrine produce net inhibition. PMID- 2902148 TI - Radiation-induced DNA damage and repair: Argonne National Laboratory Symposium. PMID- 2902149 TI - Postirradiation protection of chromosomes by linoleate. AB - Physiological concentrations of linoleate reduce the frequency of micronuclei and chromosome aberrations in mouse bone marrow cells in vivo and of micronuclei in human lymphocytes in vitro when administered one hour after exposure of the cells to gamma rays. PMID- 2902150 TI - Lethal mutations attributable to misrepair of Q-lesions. AB - Lethal mutations are induced in mammalian cells mainly, perhaps wholly, within the dose range encompassing the 'shoulder,' and may well be attributable to error prone Q-repair. PMID- 2902151 TI - Lack of inverse dose-rate effect on fission neutron induced transformation of C3H/10T1/2 cells. AB - Exponential and density-inhibited cultures of C3H/10T1/2 cells were exposed to a single dose of 0.3 Gy of fission neutrons delivered at rates ranging from 0.005 to 0.1 Gy/min. No discernible effect upon cell survival or transformation was observed by a lowering of the fission neutron dose rate in either exponential or plateau cultures. At the level of 2.3 x 10(-4) transformants per surviving cell, the RBE for neoplastic transformation was three at acute dose rates and ten at the lowest dose rate studied (0.005 Gy/min for neutrons and 0.01 Gy/min for X rays). PMID- 2902152 TI - Localization of plutonium retention in the small intestine of the neonatal rat, guinea pig, baboon and macaca after Pu-citrate ingestion. AB - The retention of Pu-citrate in the gastrointestinal wall was compared at similar post ingestion times after ingestion at 2 days of age by rats and guinea pigs and at 1 to 34 days by neonatal primates. The small intestine was the main site of the Pu retention in all species. In rats and primates, most of the Pu was retained in the distal ileum, whereas in guinea pigs it was more homogeneously distributed. In the rats, Pu was retained in the epithelial cells on villi, but in the guinea pigs and primates it was confined to the macrophages under the epithelial cells in the lacteal region. PMID- 2902153 TI - Alterations in phosphate metabolism during cellular recovery of radiation damage in yeast. AB - We have examined alterations in phosphate pools during cellular recovery from radiation damage in intact, wild-type diploid yeast cells using 31P nuclear magnetic resonance (NMR) spectroscopy. Concurrent cell survival analysis was determined following exposure to 60Co gamma-radiation. Cells held in citrate buffered saline (CBS) showed increased survival with increasing time after irradiation (liquid holding recovery, LHR) with no further recovery beyond 48 h. Addition of 100 mmol dm-3 glucose to the recovery medium resulted in greater recovery. In the presence of 5 mmol dm-3 2-deoxyglucose (2-DG), LHR was completely inhibited. NMR analyses were done on cells perfused in agarose threads and maintained under conditions similar to those in the survival studies. ATP was observable by NMR only when glucose was present in the recovery medium. In control cells, ATP concentrations increased and plateaued with increasing recovery time. With increasing radiation dose the increase in ATP was of lesser magnitude, and after 2000 Gy no increase was observed. These observations suggest that either the production of ATP in irradiated cells is suppressed or there is enhanced ATP utilization for repair of radiation damage. In CBS with 100 mmol dm 3 glucose, a dose-dependent decrease in polyphosphate (polyP) was detectable with no concurrent increase in inorganic phosphate (Pi). In the absence of an external energy source, such as glucose, there was a slight increase in Pi. This suggests that polyP may be used as an alternative energy supply. When 2-DG was present in the recovery medium, polyP decreased, but there was a simultaneous increase in Pi with increasing radiation dose and recovery time. This suggests that the polyP are hydrolyzed as a source of phosphates for repair of radiation damage. PMID- 2902154 TI - Survival of Saccharomyces cerevisiae after treatment with the restriction endonuclease Alu I. AB - Treatment of yeast cells proficient in the repair of radiation damage (Saccharomyces cerevisiae) with the restriction endonuclease Alu I leads to a positive dose-effect relationship between inactivation level and enzyme concentration. The data suggest an uptake of the active restriction enzyme into the cells and a relationship between induction of DNA double-strand breaks and cell killing. PMID- 2902155 TI - Cell death by apoptosis following X-irradiation of the foetal and neonatal rat kidney. AB - A light and electron microscopic study was undertaken to determine the type of cell death induced by X-irradiation in the developing kidney. Five-day-old Sprague-Dawley rats were exposed to a whole-body dose of either 2 or 5 Gy, and foetuses in the eighteenth day of development were exposed to a dose of 4 Gy. The kidneys were examined at 4, 8 and 24 h, and at 1 and 2 weeks post-irradiation. The dying cells from both control and treated kidneys showed the morphological features of apoptosis, a distinct form of cell death that has been identified in mammalian tissues under physiological as well as pathological conditions. Necrosis was not detected. Apoptosis was infrequent in control kidneys and insignificant in extent when compared with the proliferative activity of the cells of the superficial nephrons. There was a pronounced increase in apoptosis during the first day after irradiation. The findings are in agreement with recent ultrastructural studies which report the presence of apoptosis following irradiation of rapidly proliferating adult cell populations, and irradiation of other immature mammalian tissues. There is evidence that apoptosis involves active cellular self-destruction, and it has been suggested that activation of apoptosis might bring about selective elimination of cells with critical DNA damage in irradiated tissues, thus minimizing propagation of genetic abnormalities. PMID- 2902156 TI - Soft X-ray dosimetry and RBE for survival of Chinese hamster V79 cells. AB - Dosimetry and biological effects of 40 and 50 keV low-energy X-rays generated by a SOFTEX Model CMBW-2 apparatus were studied. Doses were measured using a thin window parallel-plate ionization chamber; beam quality was assessed using aluminum absorbers; exposure rates per unit current were determined according to the X-ray tube current and exposure times; and thermoluminescent (BeO chip) dosimeters were used to ascertain dose distributions in the irradiation field. The average correction factors for nonuniformity were calculated from the measured dose distributions. The means for ascertaining accurate exposures and doses using these methods are discussed. The dose-survival relationship of Chinese hamster V79 cells were assessed by irradiating them with 40 and 50 kV soft X-rays, 180 kV X-rays, and 60 Co gamma rays. Soft X-rays with three distinct effective energies were tested by changing the tube voltage kV and aluminium filter thicknesses; namely (1) 40 kV without filter, (2) 40 kV with a 0.2 mm thick aluminium filter and (3) 50 kV with a 0.7 mm thick aluminium filter. The effective energies obtained according to attenuation measurements using aluminium for these soft X-rays were 8.1, 11.7 and 18.5 kV, respectively. In this study the relative biological effectiveness (RBE) at 10 per cent survival compared with 60Co gamma rays ranged from 1.5 to 1.6. The RBE of 180 kV X-rays relative to 60Co gamma rays was 1.29. This study provided experimental data for the RBE of V79 cells in the intermediate energy range between hard and ultrasoft X-rays, data for which were previously reported by Goodhead and co-workers (1977, 1979, 1981). PMID- 2902157 TI - Response of human bone marrow progenitor cells to X-rays in vitro. AB - In 25 out of 33 cases the survival response of myeloid progenitor cells from fresh human bone marrows, X-irradiated in vitro in phosphate-buffered saline at 23 degrees C, was characterized by a two-term exponential relationship, with D0 values of 0.42 +/- 0.19 Gy and 1.38 +/- 0.37 Gy, respectively. In the remaining eight cases for which the colony-forming efficiency was 10 times lower, survival followed a single exponential function with D0 = 1.18 +/- 0.15 Gy. The biphasic response at 23 degrees C became a single exponential response when the temperature at irradiation was 30 or 37 degrees C. PMID- 2902158 TI - Competitive dose-modification between ascorbate and misonidazole in human and hamster cells: effects of glutathione depletion. AB - Depletion of glutathione by pretreatment with buthionine sulphoximine greatly enhances the radiosensitizing efficiency of misonidazole in mammalian cells in vitro, but a similar effect has not yet been observed in vivo. In thiol-depleted V79 Chinese hamster cells and human HT1080 fibrosarcoma cells, physiological concentrations of ascorbate greatly reduce misonidazole radiosensitization, although there is little effect of ascorbate on misonidazole sensitization in untreated cells. The effect of ascorbate on misonidazole radiosensitization is not markedly dependent on the extracellular concentration of ascorbate; this may be explained by the non-equilibrium uptake of ascorbate at different extracellular concentrations. Failure to obtain a large enhancement of misonidazole radiosensitization as a result of buthionine sulphoximine treatment in vivo may be due, in part at least, to the presence of ascorbate. PMID- 2902159 TI - Misonidazole-induced radio-resistance in normal and preirradiated jejunal mucosa. AB - Pretreatment of mice with a single dose of whole-abdomen irradiation led to a relative decrease in radiosensitivity in jejunal crypts given a second single dose of irradiation 2 months later. Hyperbaric oxygen (3.5 bars) restored the survival level to initial values, suggesting that there was radiation-induced hypoxia in the primed jejunum. However, misonidazole did not sensitize primed jejunal crypts; it reduced the radiosensitivity of both normal and primed crypts. This 'paradoxical' effect of misonidazole could well be due to the acute toxic side-effects of 1 mg/g body weight misonidazole i.p., as there was a sharp drop in the core temperature of mice immediately after drug injection. Artificially maintaining the temperature of miso-treated animals at a normal level produced crypt survival levels similar to those of both normal controls and primed controls. Thus, although the primed gut is chronically hypoxic, as suggested by the effects of hyperbaric oxygen, misonidazole is not a reliable tool for the study of this tissue hypoxia. In all in vivo experiments with misonidazole, core temperature must be controlled in order to avoid misleading interpretations of experimental results. PMID- 2902160 TI - Cell survival characteristics of a human colon adenocarcinoma cell line after photodynamic treatment: a comparison of Photofrin II and TPPS. AB - A comparison has been made of the in vitro light-activated drug cytotoxicities of two different porphyrin compounds, Photofrin II and TPPS4. An early passage human colon adenocarcinoma cell line, WiDr, has been exposed to either drug for 24 h, the excess drug washed from the cells and the cells irradiated with light using quartz-tungsten-halogen lamps. Neither light nor drug alone under the experimental conditions employed was toxic to WiDr cells. Together, considerable cytotoxicity could be seen and the shapes of the cell survival curves following exposure to either drug then irradiation with light, were similar. For equal amounts of drug in the medium, Photofrin II was a more efficient photosensitizer of WiDr cells than TPPS4, and differences in cellular uptake could only partly explain this. When the experimental procedure was changed by reducing the temperature of irradiation, a reduction in photosensitizing efficiency could be demonstrated. This was more pronounced for Photofrin II, and was seen as a change in the slope of the final portion of the survival curve; and as a change in the shoulder for TPPS4. Two different batches of the two drugs were compared and shown to give slightly different results for Photofrin II (change in shoulder) but not to differ for TPPS4. PMID- 2902161 TI - 31P NMR spectroscopy in vivo of two murine tumor lines with widely different fractions of radiobiologically hypoxic cells. AB - Energy and lipid metabolism as well as tumor pH in two murine tumor lines, the KHT and RIF-1 sarcomas, were studied using 31P NMR spectroscopy. Possible relationships between spectral parameters on the one hand and volume fraction of necrosis and fraction of radiobiologically hypoxic cells on the other were investigated. For both tumor lines the PCr and NTP beta resonances decreased and the Pi resonance increased significantly with increasing tumor volume in the volume range 100-4000 mm3. This decrease in bioenergetic status was accompanied by a decrease in tumor pH from about 7.2 to about 6.8. The NTP beta resonance and the tumor pH tended to be somewhat higher and the Pi resonance somewhat lower for the KHT than for the RIF-1 tumors. Linear relationships were found between tumor pH and Pi or (PCr + NTP beta)/Pi for both tumor lines (P much less than 0.05). The PME resonance increased slightly and the PDE resonance decreased slightly during tumor growth and were not significantly different for the KHT and the RIF 1 tumors. The volume fraction of necrosis was about 5 per cent in both lines at a tumor volume of 100 mm3 and increased to about 30 per cent (KHT) and 50 per cent (RIF-1) at a tumor volume of 4000 mm3. The fraction of radiobiologically hypoxic cells was found to increase from 12 to 23 per cent for the KHT line and from 0.9 to 1.7 per cent for the RIF-1 line when tumor volume was increased from about 200 to about 2000 mm3. The volume-dependence of the 31P NMR spectral parameters indicated increased nutritional deprivation and development of hypoxia and necrosis during tumor growth, and was thus qualitatively in good agreement with the changes observed in necrotic and hypoxic fraction. However, quantitative relationships between any spectral parameter and necrotic or hypoxic fraction across tumor lines were not found, implying that other physiological parameters and/or cellular characteristics may contribute significantly to a 31P NMR tumor spectrum. Consequently, 31P NMR spectra of untreated tumors have to be supplemented with other tumor data, e.g. rate of oxygen consumption, cell survival time under hypoxic stress and/or fraction of metabolically active, non clonogenic hypoxic cells, to be useful in quantitative determination of tumor hypoxia and hence prediction of tumor radioresistance caused by hypoxia. PMID- 2902162 TI - Hyperthermic effects on DNA repair of UV-irradiated Dictyostelium discoideum. AB - DNA repair of a lower eukaryote, Dictyostelium discoideum, has been investigated through the analysis of heat effects on cell mortality and DNA repair of UV irradiated amoeboid cells. In a wild-type strain (NC4), an increase in temperature immediately after UV irradiation resulted in an increase in cell mortality, though similar heat treatment before UV irradiation had no such effect. Similar results were obtained in another wild-type strain, HPS83. In NC4, heat treatment after UV irradiation did not inhibit the nicking of DNA strands during excision repair processes, but did inhibit the rejoining of the DNA strand breaks. Removal of thymine-containing pyrimidine dimers from DNA molecules was also depressed by heat treatment after UV irradiation. In contrast, heat treatment before UV irradiation had no effect on any stage of the nicking process, the excision of the dimers or the rejoining. On the other hand, a radiation-sensitive mutant (TW8) defective in an incision step of the excision repair process did not show an increase in cell mortality in response to heat treatment administered either before or after UV irradiation. Though the optimum temperature for cell growth of the amoebae was 23 degrees C, the critical temperature for effective enhancement of cell killing was ca. 30 degrees C. Hence we assume that the excision repair of UV-damaged DNA is selectively sensitive to heat treatment. PMID- 2902163 TI - The one-cell mouse embryo: cell cycle-dependent radiosensitivity and development of chromosomal anomalies in postradiation cell cycles. AB - One-cell mouse embryos were irradiated with X-rays at different cell cycle stages. Examination of structural chromosomal anomalies and of micronucleus formation in postradiation mitoses and interphases demonstrated cell cycle dependent radiosensitivities in the order: late G2 phase greater than G1 phase greater than S phase greater than early G2 phase greater than stage of decondensing nuclei. Comparison of the quality and quantity of chromosomal aberrations from the first to the third mitosis led to the conclusion that new chromosomal anomalies were formed in the course of postirradiation cell cycles. This hypothesis was supported by an increasing number of micronuclei from 24 to 48 h post-conception. In addition to structural chromosomal aberrations, radiation-induced chromosome loss was observed with a frequency that was obviously independent of the exposed cell cycle phase. Loss of acentric chromosome fragments and of single chromosomes contributed to the micronucleus formation. PMID- 2902164 TI - A quantitative assessment of changes in the dermal fibroblast population of pig skin after single doses of X-rays. AB - Investigations were carried out into the time- and dose-related changes in the density of fibroblasts in the dermis of irradiated pig skin. The time course of these changes in the density of fibroblast nuclei in the reticular dermis was studied from 6 to 104 weeks after irradiation with a single dose of 15.4 Gy of X rays. The largest decrease in the number of fibroblasts occurred between 12 weeks and 26 weeks after irradiation; after this time there was only a slight fall in the fibroblast number until 104 weeks when the observations ceased. At 26 weeks and later times after irradiation the reduction in the density of fibroblast nuclei in the reticular dermis was dose-dependent for single doses in the range 8.0-20.7 Gy. The dose-response curve had an initial shoulder, after which the fall in the fibroblast nuclear density was linearly related to dose. Data obtained at other times, between 26 weeks and 104 weeks after irradiation, could be fitted by the same dose-response curve. The fall in the counts of fibroblast nuclei was compared with earlier studies in pig skin. The loss of fibroblasts occurred after an initial reduction in blood flow in the pig skin but was concomitant with the general reduction in dermal thickness. PMID- 2902165 TI - Techniques to measure DNA single-strand breaks in cells: a review. AB - Alkaline sucrose sedimentation was for a number of years the standard procedure for the measurement of single-strand breaks. Some years ago a number of new techniques with improved sensitivity were introduced. The following techniques are presented and discussed: alkaline unwinding, alkaline filter elution, nucleoid sedimentation, viscoelastometry, microelectrophoresis of single cells, DNA precipitation, pulse field gel electrophoresis, fluctuation spectroscopy and nick translation. PMID- 2902166 TI - Characterization of damage in gamma-irradiated and OsO4-treated DNA using methoxyamine. AB - Unlabelled and radiolabelled methoxyamine have been used to characterize DNA damage caused by gamma-rays or by the chemical reagent osmium tetroxide (OsO4). Both treatments introduce in DNA a number of methoxyamine-binding sites proportional to the dose. Whereas the number of these sites remains constant after the OsO4 treatment it increases during postirradiation incubation; the postirradiation appearance of methoxyamine-binding sites is enhanced by the presence of methoxyamine. OsO4 treatment and gamma-irradiation also induce the formation of alkali-labile sites in DNA. Whereas the number of these sites remains constant after OsO4 treatment, it increases during postirradiation incubation and an alkaline medium accelerates their formation. A fraction of the alkali-labile sites found in gamma-irradiated DNA is methoxyamine-labile; by contrast, the OsO4-treated DNA is stable in the presence of methoxyamine. PMID- 2902167 TI - Hydroxyl radical-induced strand break formation in single-stranded polynucleotides and single-stranded DNA in aqueous solution as measured by light scattering and by conductivity. AB - Combining conductivity measurements and molecular weight determination by means of low-angle laser light scattering, we have found for the polyribonucleotides (polyuridylic acid (poly(U], polyadenylic acid (poly(A], polycytidylic acid (poly(C] and polyguanylic acid (poly(G] and for single-stranded DNA (ssDNA) that, on average, 8.5 counterions per single-strand break (ssb) are liberated under salt-free conditions. This relationship allows us to estimate, from conductivity measurements alone, G-values of single-strand break formation (G(ssb] for the polydeoxyribonucleotides (polydeoxyriboadenylic acid (poly(dA], polydeoxyribocytidylic acid (poly(dC], polydeoxyribothymidylic acid (poly(dT], polydeoxyribouridylic acid (poly(dU] and polydeoxyriboguanylic acid (poly(dG]. The following G(ssb) values (units of mumol J-1) have been obtained for anoxic conditions: poly(dA), 0.23; poly(dC), 0.14; poly(dT), 0.06; poly(dU), 0.046 and poly(dG), 0.009. Time-resolved conductivity measurements in pulse radiolysis enable us to measure the rate of strand break formation. The rate has been found to be similar for poly(dA) and ssDNA over a range of pH values. Poly(dC) and poly(dU) exhibit conductivity increase components with half-lives similar to those of poly(dA) and ssDNA at corresponding pH values. The implications of these results are discussed. PMID- 2902168 TI - Eluting solution composition affects DNA double-strand break analysis by filter elution. AB - The filter elution technique was used to assay for 137Cs-induced DNA double strand breaks (dsb) in V79 Chinese hamster cells. The elutions were performed using two different sets of lysing and eluting solutions at pH 7.2 and 9.6. The data agree with those of others who have demonstrated differences in elution profiles at pH 7.2 and 9.6. In addition, the data indicate that solution composition has a significant effect on elution. PMID- 2902170 TI - DNA double-strand break repair determines the RBE of alpha-particles. AB - Radiation-induced DNA double-strand breaks (dsb) were studied in Ehrlich ascites tumour cells (EATC) by sedimentation in neutral sucrose gradients at low centrifuge speed. Dsb induction was found to be linear with dose with a frequency of: ndsbmr-1D-1 = (11.7 +/- 2) x 10(-12)Gy-1 for 140 kV X-rays and ndsbmr-1D-1 = (19.1 +/- 4) x 10(-12)Gy-1 for 3.4 MeV 241Am-alpha-particles. Postirradiation incubation of cells under non-growth conditions leads to repair of dsb, reaching a maximum after trep = 24 h. More than 97 per cent of dsb were repaired after an X-ray dose of 25 Gy. The number of residual dsb was found to be a linear quadratic function of dose: nresmr-1 = (0.0161 +/- 0.0008) x 10(-12)Gy-2D2 for X rays and nresmr-1 = (1.2 +/- 0.7) x 10(-12)Gy-1D + (0.105 +/- 0.017) x 10(-12)Gy 2D2 for alpha-particles. Thus, after cellular repair the RBE value of alpha particles was increased from RBE = 1.6 +/- 0.4 (induction of dsb) to a dose dependent value of RBE = 2.7 +/- 0.4 (at 100 Gy alpha-particles) to 3.8 +/- 1.2 (at 10 Gy alpha-particles) for residual dsb. From the data presented it is concluded that residual dsb are a major cause for loss of the reproductive capacity of EATC after irradiation with X-rays as well as alpha-particles. PMID- 2902169 TI - The effect of modulators of radiation-induced G2 arrest on the repair of radiation-induced DNA damage detectable by neutral filter elution. AB - It has been suggested that radiation-induced G2-arrest is an extension of interphase to allow repair of DNA double-strand breaks (dsb) prior to mitosis. Cycloheximide blocks the repair of the lesions which result in radiation-induced G2 arrest. Caffeine and cordycepin reduce the duration of G2 arrest. All of these agents should therefore reduce the cell's ability to repair dsb. The influence of cycloheximide (50 micrograms/ml), caffeine (5 mM) and cordycepin (0.15 mM) on the repair of the damage detectable in DNA by neutral filter elution was determined. Chinese hamster ovary cells (CHO) were irradiated with X-ray doses of 20, 60 and 100 Gy then allowed to repair without drug treatment or in the presence of each drug for intervals up to 6 h. DNA damage repair proceeded in two phases. The fast component of the repair process (t1/2 approx. 7 min) was not modified by drug treatment; the slow component (t1/2 approx. 170 min) was unaffected by cycloheximide or cordycepin, but appeared to be inhibited by caffeine. It was concluded that: (a) the lesion which results in radiation-induced G2 arrest is not the lesion which is detectable by neutral filter elution, and (b) the influence of caffeine on dsb repair is specific to caffeine and is not mediated by a reduction in the duration of G2 arrest. PMID- 2902172 TI - Kinetics and mechanism of electron transfer between purines and pyrimidines, their dinucleotides and polynucleotides after reaction with hydrated electrons; a pulse radiolysis study. AB - The radical spectra of mixtures of thymidine 5'-monophosphate (TMP) or uridine 5' monophosphate (UMP) with adenine 5'-monophosphate (AMP) after hydrated electron attack, measured from 5 to 3000 microsecond after pulse radiolysis, can only be described in terms of the radical spectra of the nucleotides if an electron transfer is taken into account from the purine radical anion to the pyrimidine, resulting in the formation of a pyrimidine radical anion. From analysis of the spectra of the dinucleoside phosphates ApU, dApT and dCpdA after eaq- attack it follows that the electron-donating species is the purine radical anion (A-.) rather than the protonated purine radical. The electron transfer competes with the fast protonation of the purine radical anion: A-. + py----A + py.- and A-. + H2O in equilibrium AH. respectively. The electron transfer is found to have a diffusion-controlled reaction rate constant of approximately 1.2 X 10(10) for TMP and 3.5 X 10(9) dm3 mol-1 s-1 for UMP. PMID- 2902171 TI - Rate constants for the reactions of halogenated organic radicals. AB - Absolute rate constants have been measured by means of pulse radiolysis for the reactions of various halogenated aliphatic compounds (ethane derivatives, including the anaesthetics halothane, enflurane, isoflurane and methoxyflurane) with hydrated electrons and .OH radicals, the reactions of halogenated carbon centered radicals, derived thereby, with molecular oxygen, and the reactions of halogenated peroxyl radicals with various antioxidants (ascorbate, chlorpromazine, promethazine, propyl gallate, ABTS) in aqueous solutions. All oxygen addition reactions occur essentially diffusion-controlled. This finding is correlated with the stereoelectronic properties of the primary carbon-centred radicals. The oxidative power of the halogenated peroxyl radicals reflects the inductive -I effect of the halogens and accordingly increases with the degree of halogen substitution, with fluorine substituents being particularly effective. The peroxyl radicals derived from freon 113, namely CClF2CClFOO. and CCl2FCF2OO., have been identified as the best oxidants among these species. PMID- 2902175 TI - Application of a freeze-thaw technique to studies of radiation-induced cell transformation. PMID- 2902174 TI - Membrane lipids of B16 melanoma cells and heat-resistant variants. AB - Membrane lipid composition and fluidity of a series of B16 melanoma cell variants with increased resistance to heat were analysed for changes within the lipid component that may contribute to the acquisition of heat resistance. Within one series of heat-resistant lines the cholesterol content of the cells decreased as their heat resistance increased. The most heat-resistant line, WH75, had 40 per cent less cholesterol than the parent line. No change in the composition of phospholipid fatty acids was found. An increased level of membrane fluidity in WH75 was demonstrated by electron paramagnetic resonance using 5- or 12-doxyl stearic acid. When challenged by heat the increase in membrane fluidity was similar for WH75 and for the parent line. Thus the increased heat resistance of the variants is probably not due to their ability to adapt to heat challenge by increasing membrane thermostability. The inverse relationship between heat resistance and cholesterol content was not demonstrated in two other series of heat-resistant variants. The cholesterol decrease, therefore, is not a universal response of cells as they acquire heat resistance. PMID- 2902176 TI - Netherlands, Belgian and Swedish Radiobiological Societies, Association for Radiation Research and Radiobiology, Committee of the British Institute of Radiobiology. Abstracts. Joint meeting. Noordwijkerhout, The Netherlands, 18-20 May 1988. PMID- 2902173 TI - The effect of artificially induced hyperglycemia on the radiation response of the Lewis lung and EMT6 tumor models. AB - The effect of hyperglycemia, induced by administration of glucose, on the radiation response of the Lewis lung and EMT6 tumor models has been evaluated. Neither acute (single i.p. injection of 8 mg/glucose) nor chronic (multiple i.p. injections of 6 mg/g glucose plus glucose in the water bottles) administrations of glucose increased the radiation response of either tumor. A combination of a single i.p. injection of glucose and a reduction of the O2 content of the inspired gas to 10 per cent did by itself reduce cell survival by 55-75 per cent in the EMT6 and 80-90 per cent in the Lewis lung carcinoma. However, this treatment had little effect on the shape of the radiation dose-response curve, and simply gave rise to a parallel shift of the survival curve, indicating that this treatment had little or no specificity for hypoxic cells. PMID- 2902177 TI - LY141865: a relatively selective DA2 agonist with complex ocular activity. AB - LY141865 (LY), an ergoline derivative, was investigated for ocular effects in rabbits and monkeys. LY lowered intraocular pressure (IOP) bilaterally in monkeys and rabbits, prevented the bilateral rise in IOP caused by oral waterloading in rabbits and slowed the rate of IOP recovery bilaterally in rabbits. The ocular hypotensive activity of LY in rabbits was inhibited by sympathectomy and pretreatment with sulpiride. Since LY has cardiovascular effects that are centrally mediated, ocular responses may also be mediated, in part, by an action in the CNS. PMID- 2902178 TI - Effect of antacid and H2 receptor antagonists on the intestinal absorption of folic acid. AB - Intestinal folic acid transport is a saturable process with a pH optimum of 5.5 to 6.0. Because of the possible effects of antacids and acid-lowering drugs on the pH of the proximal small intestine, the influence of these drugs on folic acid absorption was studied by using tritium-labeled pteroylmonoglutamic acid (PGA) in 30 subjects (21 women, nine men) of 56 to 89 years of age. Both cimetidine and an antacid containing aluminum and magnesium hydroxide reduced folate absorption from a liquid formula meal (p less than 0.01, p less than 0.001, respectively). Although ranitidine also caused a fall in folic acid absorption from the liquid meal, the change was not statistically significantly different from when PGA was given with the meal alone. Both histamine receptor antagonists tended to maintain a high intraluminal pH in the proximal small intestine after meals, which in part could explain the inhibition of folate absorption. However, neither drug was found to chemically interact with folic acid, and neither drug inhibited the dihydrofolate reductase. The antacid was found to precipitate folic acid at a pH of greater than 4.0, thus removing it from the aqueous phase. This appears to be the explanation for the lowered folate absorption in the presence of antacid. Although the effects of these drugs on reducing folic acid absorption were relatively small, such reductions could become clinically significant in chronic antacid or H2 receptor antagonist use or intensive antacid or H2 receptor antagonist use by individuals eating diets that are marginal in folate content. PMID- 2902179 TI - Localization of 3-hydroxy-3-methylglutaryl CoA reductase and 3-hydroxy-3 methylglutaryl CoA synthase in the rat liver and intestine is affected by cholestyramine and mevinolin. AB - In the normal fed rat, both 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) synthase and HMG-CoA reductase are found in high concentrations in hepatocytes that are localized periportally. The majority of the liver cells show little or no evidence of either enzyme. Addition of cholestyramine and mevinolin to the diet resulted in all liver cells showing strong positive staining for both HMG-CoA reductase and HMG-CoA synthase. These two drugs increased the hepatic HMG-CoA reductase and HMG-CoA synthase activities 92- and 6-fold, respectively, and also increased the HMG-CoA reductase activity in intestine, heart, and kidney 3- to 15 fold. We used immunofluorescence and avidin-biotin labeled antibody to localize HMG-CoA reductase in the rat intestine. In rats fed a normal diet, the most HMG CoA reductase-positive cells were the villi of the ileum greater than jejunum greater than duodenum. Crypt cells showed no evidence of HMG-CoA reductase. Addition of cholestyramine and mevinolin to the diet led to a dramatic increase in the concentration of HMG-CoA reductase in the apical region of the villi of the ileum and jejunum and in the crypt cells of the duodenum. Hence these two drugs affected both the relative concentration and distribution of intestinal HMG CoA reductase. Cholestyramine and mevinolin feeding induced in the liver, but not intestine, whorls of smooth endoplasmic reticulum that were proximal to the nucleus and contained high concentrations of HMG-CoA reductase. Administration of mevalonolactone led to the rapid dissolution of the hepatic whorls within 15 min, at a time when there is little or no change in the mass of HMG-CoA reductase. We conclude that the whorls are present in the livers of rats fed cholestyramine and mevinolin because the cells are deprived of a cellular product normally synthesized from mevalonate. PMID- 2902180 TI - Serum proteinase inhibitors and glutamyl transferase in patients suffering from cancer of the gastrointestinal tract, lung, breast and cervix. PMID- 2902181 TI - Clinical evaluation of serum gamma glutamyl transpeptidase in Thai patients with hepatic disease. PMID- 2902182 TI - Somatostatin levels and binding in duodenal mucosa of rabbits with ligation of the pancreatic duct. AB - Atrophy of the exocrine pancreas was induced in rabbits by pancreatic duct ligation. Somatostatin concentration and binding in cytosol from rabbit duodenal mucosa were studied after 6 and 14 weeks of pancreatic duct ligation. Somatostatin-like immunoreactivity was significantly increased in the duodenal mucosa in both periods. Scatchard analysis showed a parallel increase in the number of binding sites rather than a change in their affinity. The physiological significance of these findings remains to be clarified. PMID- 2902183 TI - Cellular induction of chronic allotype suppression of IgG2a in Ighb/b homozygous mice and its abrogation by in vivo treatment with anti-CD8 monoclonal antibody. AB - We report here the successful induction of allotype suppression in homozygous Ighb/b mice (CB20 or C57BL/6) by neonatal injection of T splenocytes from Igha congenic sensitized mice (BALB/c or BC8, respectively). The sensitization of the T cell donors was achieved by two intravenous injections of B splenocytes from Ighb congenic mice. Treated homozygous Ighb/b mice developed, as of 16-24 wk of age, a chronic suppression of Igh-1b expression (IgG2a of Ighb haplotype). The other productions tested (IgM, IgD, and IgA) of Ighb haplotype were unaffected. In vivo treatment with cytotoxic anti-CD4 or anti-CD8 mAb of mice subjected to chronic Igh-1b suppression clearly showed that CD8+ lymphocytes (suppressor or cytotoxic cell) were essential for the maintenance of the suppression. The suppression was indeed abrogated after a 1-wk treatment with anti-CD8 mAb containing culture supernatant, whereas, the anti-CD4-treated mice continued to be subjected to suppression. This anti-CD8 in vivo treatment was shown to have no effect on thymus but to severely reduce the percentages of CD8+ cells in spleen and in peripheral blood without affecting the percentages of CD4+ cells, leading to a large and rapid Igh-1b expression (up to 0.5 mg per ml of serum, the day after the end of the treatment). This suppression abrogation, and thus the Igh-1b expression, was either transient or permanent. When it was transient, a second 1 wk treatment with anti-CD8 mAb containing culture supernatant induced once again a rapid and significant production of Igh-1b (up to 0.3 mg of Igh-1b per ml of serum). PMID- 2902185 TI - Dissecting human T cell responses against Bordetella species. AB - To identify the minimal structures that may be important for the creation of a synthetic and/or recombinant vaccine against whooping cough, human T cell clones were obtained against Bordetella antigens. Cloned peripheral blood T lymphocytes from an immune donor were grown in IL-2 and tested for proliferation in response to inactivated Bordetella species (B. pertussis, B. parapertussis, and B. bronchiseptica) and mutants deficient for the expression of virulence-associated antigens. All the T cell clones obtained were CD4+8- and recognized specifically the Bordetella antigens when presented by autologous B cells. On the basis of the responsiveness to the whole inactivated bacteria, it was possible to cluster the 12 clones obtained into four groups with the following specificity: (1) filamentous hemagglutinin (FHA); (2) B. pertussis-specific antigens; (3) virulence-associated Bordetella-specific antigens; and (4) nonvirulence associated Bordetella-specific antigens. Using two new B. pertussis deletion mutants, clone 6 (representative of cluster 1) was found to recognize the COOH terminus of FHA. Furthermore, three out of four clones of cluster 3 were specifically stimulated by the soluble 69-kD protein from the outer membrane of B. pertussis. Surprisingly, none of the twelve clones obtained by stimulation in vitro with whole inactivated bacteria recognized pertussis toxin (PT), which is believed to be the most important protein to be included in an acellular vaccine. However, when a new generation of clones was obtained using soluble PT as the in vitro stimulus, it was observed that 11 clones of this group recognized this antigen. Thus, PT does not seem to be the most representative antigen on the whole inactivated bacteria, although T cell memory against PT exists in a donor who had the disease several years ago. PMID- 2902184 TI - Purification, characterization, and pathogenicity of Moraxella bovis pili. AB - Pilins composed of the alpha or beta pilins of Moraxella bovis strain Epp63 were purified, subjected to chemical or enzymatic cleavage, and the resulting fragments sequenced by automated Edman degradation. alpha Pilin was found to be a 155-amino-acid polypeptide with a single intramolecular disulfide bridge. The beta pilin amino acid sequence substantiated the previously reported structure derived from the beta pilin gene DNA sequence, and indicated that the alpha and beta pilins of this strain are approximately 70% homologous. DNA hybridization studies of genomic DNA from the alpha- and beta-piliated variants of strain Epp63 indicated that the expression of the two pilin types was governed by an oscillating mechanism of chromosomal rearrangement. The alpha and beta pili were evaluated serologically and found to exhibit approximately 50% shared antigenicity, indicating that regions of conserved and heterologous sequence specify both type-specific and crossreacting epitopes. The pathogenicity of the alpha- and beta-piliated variants was studied by ocular inoculation of calves eyes; beta-piliated organisms were significantly more infectious than alpha piliated organisms, indicating that beta pili confer, or are associated with, a relative advantage during the first stages of ocular infection. Preliminary analysis of other M. bovis strains suggests that each strain produces two types of pilin, and that this property may be characteristic of the species. PMID- 2902188 TI - Establishing paternity using minisatellite DNA probes when the putative father is unavailable for testing. AB - A paternity case involving a putative father who had died a few years earlier in an automobile accident was referred to the laboratory for testing. The child and his mother, the deceased's parents, and nine of the deceased's siblings were available for analysis. As previously reported, paternity testing using red blood cell groups, human leukocyte antigens (HLA), red blood cell enzymes, serum proteins, and immunoglobulin allotypes gave a cumulative paternity index of 43,300 and a combined probability of paternity equal to 99.998%. RFLP analysis using Hinf I and Sau 3A single digests and the minisatellite deoxyribonucleic acid (DNA) probes 15.1.11.4 and 6.3 showed no exclusion of paternity and gave nearly conclusive evidence that the putative father was the biological father of the child. PMID- 2902186 TI - The V gamma locus of the human T cell receptor gamma gene. Repertoire polymorphism of the first variable gene segment subgroup. AB - Southern blot analysis using a genomic probe of the human TCR-gamma chain first variable gene subgroup (V gamma I) was performed on DNA samples from both parents of 36 healthy Caucasian families. Two types of polymorphisms were found in these 72 unrelated DNA samples: three repertoire polymorphisms and two restriction fragment length polymorphisms (RFLP). In all cases, Mendelian inheritance of these polymorphisms was demonstrated. The most frequent repertoire polymorphism consists in the lack of the V gamma 4 and V gamma 5 segments. In 16% of chromosomes, the Eco RI and Taq I restriction fragments corresponding to V gamma 4 and V gamma 5 were lacking, with no additional bands. In these cases, a decrease of 10 kb was observed in the Bam HI fragment containing all V gamma I segments as compared with samples containing V gamma 4-V gamma 5 segments. To better understand this polymorphism, which takes place in a previously incompletely defined region, the central part of the V gamma I region, including the polymorphic V gamma 4-V gamma 5 segments, was cloned. This allowed us to localize precisely the V gamma 5 segment and thus complete the description of the V gamma I region. A striking homology of DNA and deduced amino acid sequences is present between V gamma 2 and V gamma 4 and between V gamma 3 and V gamma 5, much higher than that observed between V gamma 2 and V gamma 3 and between V gamma 4 and V gamma 5. The differences in nucleotide sequence occur mainly in the intron and three hypervariable regions. These results strongly suggest a gene duplication relationship between the segments V gamma 2-V gamma 3 and the segments V gamma 4-V gamma 5. The most frequent RFLP documented in this study is due to the combined absence of the Eco RI and the Taq I sites located in the noncoding region between V gamma 3 and V gamma 4. The haplotypic frequence of this RFLP is 6.9% of the general population. As the gamma/delta receptor may play an important role in immunological response, the biological relevance of the high degree of polymorphism occurring in the V gamma I region, as well as its possible association with some immune disturbances, should be further explored. PMID- 2902189 TI - Regulatory changes regarding physician's assistant clinical practice. PMID- 2902187 TI - Toxin, toxin-coregulated pili, and the toxR regulon are essential for Vibrio cholerae pathogenesis in humans. AB - Isogenic mutant strains of V. cholerae O1 lacking elements of a genetic regulon controlled by toxR and implicated in virulence were tested in volunteers. A deletion mutation in ctxA, the gene encoding the A subunit of cholera toxin, markedly attenuated disease symptoms without affecting intestinal colonization. Deletion of toxR, the gene encoding the cholera toxin-positive regulatory protein resulted in a diminution in colonizing capacity. A deletion mutation in tcpA, encoding the major subunit of the toxin coregulated pilus (regulated by toxR), abolished the colonizing capacity of this strain. These results show for the first time the role of a specific pilus structure in colonization of the human intestine by V. cholerae O1 and exemplify the significance of a genetic regulon in pathogenesis. PMID- 2902190 TI - Analysis of alkyl nitrites by capillary gas chromatography-mass spectrometry. PMID- 2902191 TI - Antigenic relationship between hantaviruses analysed by immunoprecipitation. AB - Antigenic relationships between seven hantaviruses isolated in Sweden, Belgium, Korea, European U.S.S.R. and Asian U.S.S.R. were studied by radioimmunoprecipitation assays (RIPA) and indirect immunofluorescence tests (IFT). Animal immune sera and haemorrhagic fever with renal syndrome (HFRS) patient sera from the above countries were used. The strains fell into three antigenic groups by both RIPA and IFT: nephropathia epidemica (NE)-type, Korean haemorrhagic fever (KHF)-type and urban rat-type. This antigenic grouping conforms to the clinical grouping of the respective HFRS patients. The major cross-reactive antigen between the antigenic groups was the nucleocapsid protein. Of the two viral glycoproteins, the G2 exhibited weak cross-reactivity between the groups, while the G1 protein appeared to be the least cross-reactive. Patient sera collected at different intervals after the onset of disease showed a marked difference in their capacity to immunoprecipitate the homologous viral glycoproteins, although by IFT all sera had high titres. Host species-related antibody response differences were found by both RIPA and IFT. Using patient sera, a one-way cross-reactivity was seen between the NE-type and the KHF-type viruses. However, animal immune sera clearly demonstrated a reciprocal cross reactivity between the two virus groups. PMID- 2902192 TI - Virus isolation and immune studies in a cohort of homosexual men. AB - Virus shedding was detected in 77% of homosexual subjects and in only 6% of heterosexual controls. The overall virus isolation rate in homosexual subjects was not significantly different among HIV-seropositive (79%) and HIV-seronegative (74%) individuals. In about 20% of homosexual subjects, virus shedding from multiple sites was observed. The most frequently isolated virus was cytomegalovirus (CMV) (41%), followed by enteroviruses (23%), herpes simplex virus (HSV) (7%), and adenoviruses (6%). In the control group, about 50% of subjects were seronegative for HSV-1 and 2, and about 70% were negative for CMV and Epstein-Barr virus (EBV). Only 2% of homosexuals were seronegative for CMV, about 5% for HSV-1 and 2, and about 20% for EBV. No differences were found in antibody levels against varicella-zoster virus (VZV) among the control and homosexual groups. The proportion of seronegatives for Coxsackie and hepatitis viruses was significantly higher in control than in homosexual subjects. However, no differences in the proportion of seronegatives for measles, mumps, and rubella were observed. No HIV-antibody-negative individual was detected with an OKT4/OKT8 ratio of less than 0.75. On the other hand, only HIV-positive subjects, with a ratio of less than 0.75, had high serum IFN alpha titers. The results suggest that the high rate of virus shedding among HIV-negative homosexual subjects might be a factor in the development of AIDS in this high-risk population. PMID- 2902194 TI - Effect of taurine on neurotransmitter release from insect synaptosomes. AB - The effect of taurine on the release of [3H]acetylcholine ([3H]ACH) and [3H]gamma aminobutyric acid ([3H]GABA) from preloaded locust synaptosomes has been studied. Veratridine (100 microM) and K+ (100 mM) both evoked [3H]ACh release and this was reduced in a concentration-dependent manner by taurine (5, 10, and 20 mM). In contrast to this, veratridine induced no observable release of [3H]GABA, and the response to K+ was slight. In the presence of taurine, however, a concentration dependent enhancement of [3H]GABA release was observed. Since nipecotic acid (1 mM), an inhibitor of neuronal GABA uptake, also revealed [3H]GABA release induced by veratridine, it is suggested that both this effect and that of taurine are due to prevention of GABA reuptake. These results suggest that taurine may act as a neuromodulator in insects. PMID- 2902193 TI - Neural and glial phenotypic expression by neural crest cells in culture: effects of control and presumptive aganglionic bowel from ls/ls mice. AB - The enteric nervous system is formed by cells that migrate to the bowel from the neural crest. Previous experiments have established that avian crest cells in vitro will colonize explants of murine bowel and there give rise to neurons. It has been proposed that phenotypic expression by the crest-derived precursors of enteric neurons and glia is critically influenced by the microenvironment these cells encounter within the gut. To test this hypothesis, quail crest cells were cocultured with explants of control or presumptive aganglionic bowel from the ls/ls mutant mouse, and the effects of the enteric tissue on five phenotypic markers of crest cell development were followed. Aganglionosis develops in the terminal region of the colon of the ls/ls mouse because viable crest-derived neural and glial precursors fail to colonize this tissue. Expression of the phenotypic markers in the cocultures was compared with that in cultures of crest alone, crest plus neural tube, and gut grown alone. The markers examined were melanogenesis and immunostaining with antisera to 5-hydroxytryptamine (5-HT) and tyrosine hydroxylase (TH) and the monoclonal antibodies, NC-1 and GlN1. Explants of control, but not presumptive aganglionic ls/ls gut were found to increase the incidence of the expression of 5-HT and NC-1 immunoreactivities; moreover, especially near the gut, the assumption of a neuronal morphology by 5-HT-, NC-1-, and GlN1-immunoreactive cells was also increased. Coincidence of expression of 5 HT with NC-1 and GlN1 immunoreactivities was observed. The effect of the bowel was selective in that the expression of TH immunoreactivity, which is not a marker of mature enteric neurons, was reduced rather than enhanced. The effect of enteric explants on crest cell development was specific in that it was not mimicked by explants of metanephros, which inhibited expression of 5-HT immunoreactivity and the acquisition of a neuritic form by NC-1-immunoreactive cells. It is concluded that the enteric microenvironment affects the phenotypic expression of subsets of crest cells and that this action of the bowel is manifested in vitro. The inability of presumptive aganglionic gut from ls/ls mice to influence neural phenotypic expression may be due to the failure of this tissue to produce putative factor(s) required for the effect or to the inability of the crest-derived precursor cells to migrate into the abnormal enteric tissue. PMID- 2902195 TI - Long-term effects of RU24722 on tyrosine hydroxylase of the rat brain. AB - The effects of RU24722 (14,15-dihydro-20,21-dinoreburnamine-14-ol) on tyrosine hydroxylase in central catecholaminergic neurons were studied in rats treated with different quantities of the molecule, and a time course was done for the minimal dose that gave the maximal effect. RU24722 induced increases in tyrosine hydroxylase activities and specific protein content in noradrenergic cells of the locus ceruleus and decreased all these parameters in dopaminergic neurons of the substantia nigra and ventral tegmental area. The results pointed out that the specific activity of newly synthesized tyrosine hydroxylase in the loci cerulei was potentially greater but was not expressed "in vivo" except 7 days after injection. The phenotypic specificity and the time course pattern of the action could be considered as a consequence of an induction mechanism. The comparison of long-term change in tyrosine hydroxylase values after piperoxane, RU24722, clonidine, and combined RU24722-clonidine treatment demonstrated that an activation during a few hours did not induce tyrosine hydroxylase in central noradrenergic neurons. Clonidine antagonized the activating effect of RU24722 following its injection but did not affect its long-term induction properties. PMID- 2902196 TI - Effect of ischemia on the in vivo release of striatal dopamine, glutamate, and gamma-aminobutyric acid studied by intracerebral microdialysis. AB - We have previously described a marked attenuation of postischemic striatal neuronal death by prior substantia nigra (SN) lesioning. The present study was carried out to evaluate whether the protective effect of the lesion involves changes in the degree of local cerebral blood flow (ICBF) reduction, energy metabolite depletion, or alterations in the extracellular release of striatal dopamine (DA), glutamate (Glu), or gamma-aminobutyric acid (GABA). Control and SN lesioned rats were subjected to 20 min of forebrain ischemia by four-vessel occlusion combined with systemic hypotension. Levels of ICBF, as measured by the autoradiographic method, and energy metabolites were uniformly reduced in both the ipsi- and contralateral striata at the end of the ischemic period, a finding implying that the lesion did not affect the severity of the ischemic insult itself. Extracellular neurotransmitter levels were measured by microdialysis; the perfusate was collected before, during, and after ischemia. An approximately 500 fold increase in DA content, a 7-fold increase in Glu content, and a 5-fold increase in GABA content were observed during ischemia in nonlesioned animals. These levels gradually returned to baseline by 30 min of reperfusion. In SN lesioned rats, the release of DA was completely prevented, the release of GABA was not affected, and the release of Glu was partially attenuated. However, excessive extracellular Glu concentrations were still attained, which are potentially toxic. This, taken together with the previous neuropathological findings, suggests that excessive release of DA is important for the development of ischemic cell damage in the striatum. PMID- 2902197 TI - Regulation of glutamate and aspartate release from slices of the hippocampal CA1 area: effects of adenosine and baclofen. AB - Glutamate and/or aspartate is the probable transmitter released from synaptic terminals of the CA3-derived Schaffer collateral, commissural, and ipsilateral associational fibers in area CA1 of the rat hippocampal formation. Slices of the CA1 area were employed to test the effects of adenosine- and gamma-aminobutyrate (GABA)-related compounds on the release of glutamate and aspartate from this projection. Under the conditions of these experiments, the release of glutamate and aspartate evoked by 50 mM K+ was more than 90% Ca2+-dependent and originated predominantly from the CA3-derived pathways. Adenosine reduced the K+-evoked release of glutamate and aspartate by a maximum of about 60%, but did not affect the release of GABA. This action was reversed by 1 microM 8-phenyltheophylline. The order of potency for adenosine analogues was as follows: L-N6 phenylisopropyladenosine greater than N6-cyclohexyladenosine greater than D-N6 phenylisopropyladenosine approximately equal to 2-chloroadenosine greater than adenosine much greater than 5'-N-ethylcarboxamidoadenosine. 8-Phenyltheophylline (10 microM) by itself enhanced glutamate/aspartate release, whereas dipyridamole alone depressed release. These results support the view that adenosine inhibits transmission at Schaffer collateral-commissural-ipsilateral associational synapses mainly by reducing transmitter release and that these effects involve the activation of an A1 receptor. Neither adenosine, L-N6 phenylisopropyladenosine, nor 8-phenyltheophylline affected the release of glutamate or aspartate evoked by 10 microM veratridine. The differing effects of adenosine compounds on release evoked by K+ and veratridine suggest that A1 receptor activation either inhibits Ca2+ influx through the voltage-sensitive channels or interferes with a step subsequent to Ca2+ entry that is coupled to the voltage-sensitive Ca2+ channels in an obligatory fashion. Neither baclofen nor any other agent active at GABAB or GABAA receptors affected glutamate or aspartate release evoked by elevated K+ or veratridine. Therefore, either baclofen does not inhibit transmission at these synapses by depressing transmitter release or else it does so in a way that cannot be detected when a chemical depolarizing agent is employed. PMID- 2902198 TI - Astrocytes from forebrain, cerebellum, and spinal cord differ in their responses to vasoactive intestinal peptide. AB - Astrocytes from cortex, cerebellum, and spinal cord responded to isoproterenol and vasoactive intestinal peptide (VIP) with increases in intracellular cyclic AMP levels. The response to VIP was as great as that to isoproterenol in cortical astrocytes (180-fold and 185-fold, respectively), and the effect of VIP in combination with isoproterenol was partially additive. Spinal cord astrocytes also responded to VIP and isoproterenol with equal potency (seven- to ninefold and eight- to 13-fold, respectively), but the level of response was much smaller than in cortex. Spinal cord astrocytes were synergistic in their response to VIP and isoproterenol. The response to VIP was lowest in cerebellar astrocytes (only threefold), and no additivity was observed when VIP was added together with isoproterenol. A small response to alpha-melanocyte stimulating hormone (alpha MSH) was also observed in cortex and cerebellum, but not in spinal cord. Somatostatin inhibited the response to isoproterenol in cortex and cerebellum, but had no effect in spinal cord. The results from the above study show that astrocytes obtained from these three regions of the rat CNS express quite different responses to VIP and alpha-MSH and further point to possible astrocyte heterogeneity. PMID- 2902199 TI - Cortical somatostatinergic system not affected in Alzheimer's and Parkinson's diseases. AB - A reduction in the levels of somatostatin-like immunoreactivity (SLI) and somatostatin binding sites in the cerebral cortex has been previously reported to occur in Alzheimer's disease (AD) and Parkinson's disease with associated dementia. In the present study, the levels of both SLI and high affinity [3H]somatostatin binding sites have been measured in the frontal (Brodmann area 9) and temporal (Brodmann area 21) cortices in patients with presenile and senile Alzheimer's disease, and in mentally normal and cognitively impaired cases of Parkinson's disease. The results were compared with those obtained from a group of normal patients matched for age and postmortem delay. No significant changes in SLI or somatostatin binding in the frontal and temporal cortex were found between any of the disease groups. These results suggest that involvement of the somatostatinergic system in AD or Parkinson's disease is not a consistent or primary neurochemical feature of these diseases. PMID- 2902200 TI - Sites of antagonist action on N-methyl-D-aspartic acid receptors studied using fluctuation analysis and a rapid perfusion technique. AB - 1. Mouse hippocampal neurons in dissociated culture were grown at low density on previously plated hippocampal glial cell cultures and voltage clamped using the tight seal whole-cell patch-clamp technique. Flow pipes were used to rapidly exchange the extracellular solution, and to apply N-methyl-D-aspartic acid (NMDA) and some NMDA antagonists. Fluctuation analysis was used to estimate changes in the behavior of NMDA-activated ion channels during application of antagonists. In the presence of NMDA control spectra were well fit by single Lorentzian functions consistent with mean open times of 5-6 ms. 2. Two antagonists thought to act at the NMDA receptor agonist recognition site, 2-amino-5-phosphonovaleric acid (AP5) and kynurenic acid, did not produce changes in the mean open time or single channel conductance, consistent with their action as competitive antagonists. Onset of antagonism and recovery from the action of both AP5 and kynurenic acid was rapid and complete within 1 s. However, raising the extra-cellular glycine concentration, from 1 microM to 1 mM, reduced the potency of 100 microM kynurenic acid as an NMDA antagonist, suggesting that kynurenate has an additional action as a competitive antagonist at the glycine modulatory site on NMDA receptor channels. 3. In the presence of 150 microM magnesium NMDA spectra recorded at -60 mV were fit by double Lorentzian functions, consistent with single-channel events consisting of bursts of openings lasting 3.3 ms in duration, interrupted by blocking and unblocking events of average duration 0.18 ms. The onset and recovery from magnesium antagonism was rapid, and complete within 1 s, but was highly voltage dependent and at +40 mV magnesium (150 microM) failed to produce NMDA antagonism. These results are consistent with a voltage-dependent channel block of NMDA receptor channels produced by binding of magnesium to a site within the ion channel. 4. Zinc (30 microM) was a potent NMDA antagonist at both -60 and +40 mV, and at either potential appeared to reduce the mean open time of NMDA activated ion channels from about 5 ms to approximately 3 ms. Over the frequency range measured, 1-1,000 Hz, NMDA spectra were well fit by single Lorentzians during zinc antagonism, in contrast to results obtained with magnesium. The mean single channel conductance also decreased in the presence of zinc to approximately 75% of control. Onset of antagonism and recovery from the action of zinc was rapid and complete within 1 s.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2902201 TI - An iontophoretic study of single somatosensory neurons in rat granular cortex serving the limbs: a laminar analysis of glutamate and acetylcholine effects on receptive-field properties. AB - 1. Glutamate, acetylcholine (ACh), and bicuculline were delivered by iontophoretic pipettes to the 545 neurons described in the preceding paper. Their response properties were examined to determine the effect of these compounds on the behavior of neurons in rat somatosensory cortex. 2. The responses to glutamate covered a broad range. Some cells were completely depolarized by small amounts of this excitatory amino acid, whereas others were extremely insensitive requiring in excess of 100 nA to be excited. This range of sensitivities was seen throughout all cortical layers. 3. Glutamate was most effective in uncovering new receptive fields or in enhancing preexisting somatic responses in the bottom of layer II/III and in layer IV. Receptive fields uncovered by glutamate had properties comparable to receptive fields observed without drugs. Overall, glutamate enhanced the ability of afferent inputs to drive 39% of the neurons tested. 4. In 61% of the cells tested with glutamate there was no evidence of somatic input even during excitation with glutamate. Of 50 cells displaying receptive fields, only two were enlarged by treatment with glutamate. For 36 other cells receptive fields of normal dimensions were uncovered during glutamate administration. 5. Bicuculline uncovered more somatic inputs than either glutamate or ACh, leaving only 37% of 86 cells tested without evidence of excitatory inputs from the skin. Bicuculline produced an average receptive-field enlargement of 8.7 times in 11 of 56 cells tested. This drug acted uniformly throughout the cortical layers. 6. ACh excited 36.9% of the 360 cells tested. Those excited tended to be located in laminae Vb and VIb. The effects of ACh on afferent response properties could not be predicted from its ability to excite a cell. The magnitude of the response to 100 nA of ACh varied with the laminar position of the cell being tested, being weakest in layer II/III and greatest in layer Vb. 7. Overall, 34.2% of 263 cells showed changes in afferent drive during ACh treatment. ACh enhanced the responses to somatic stimulation most frequently in laminae IV and V. 8. Of the 90 neurons tested for long-term effects, 27% displayed effects of ACh that significantly outlasted the duration of the ACh administration. In 18% of these, changes lasted for greater than 5 min, sometimes remaining altered for the duration of the time that the cell was studied. These long-term changes in excitability were generally produced by administration of ACh during the time that the cell was excited by glutamate or by somatic stimulation. PMID- 2902202 TI - Dopaminergic and indoleamine-accumulating amacrine cells express GABA-like immunoreactivity in the cat retina. AB - Colocalization of indoleamine uptake and GABA-like immunoreactivity was studied in the cat retina. Consecutive, semithin sections were incubated in antisera to either 5-HT (5-hydroxytryptamine) or GABA. More than 90% of all 5-HT-accumulating amacrine cells expressed GABA-like antigens. With the same approach, the colocalization of 5-HT uptake and GABA-like immunoreactivity was studied in rabbit and 75-80% of the 5-HT-accumulating amacrine cells expressed GABA-like immunoreactivity, thus confirming a previous study (Osborne and Beaton, 1986). Since, in both cat and rabbit, endogenous 5-HT could not be found by immunocytochemistry, one must consider the possibility that some GABAergic amacrine cells take up indoleamines. In the cat retina, antibodies against tyrosine hydroxylase (TH) label dopaminergic amacrine cells (Oyster et al., 1985). By incubating consecutive, semithin sections in antisera to either TH or GABA, it was found that 84% of the dopaminergic amacrine cells also expressed GABA-like immunoreactivity. GABA-like immunoreactivity and 3H-muscimol uptake were found to be colocalized in more than 90% of the amacrine cells labeled. However, dopaminergic amacrine cells did not accumulate 3H-muscimol. Evidence is presented from colocalization studies for 2 types of interplexiform cell in the cat retina. One is stained by GABA-like immunocytochemistry and by 3H-muscimol uptake. The other is the dopaminergic amacrine cell, which also expresses GABA like immunoreactivity, but does not accumulate 3H-muscimol. PMID- 2902203 TI - NMDA- and non-NMDA-receptor components of excitatory synaptic potentials recorded from cells in layer V of rat visual cortex. AB - The pharmacological properties of excitatory synapses on pyramidal cells in layer V of rat visual cortex were investigated by recording EPSPs intracellularly in tissue slices. The EPSPs were evoked by electrically stimulating cells in layer II/III or axons in white matter. All of the layer V neurons were pyramidal in nature as determined by injections of Lucifer yellow or by electrophysiological criteria. Application of the broadly acting antagonists kynurenic acid and gamma D-glutamylglycine reversibly antagonized the EPSPs from both presynaptic sources in a dose-dependent manner: 1 and 5 mM kynurenic acid produced 63 and 79% reductions, respectively, of control responses. The specific NMDA antagonist APV (50 microM) caused a small reduction in peak amplitude and a more significant reduction in the duration of the falling phase of EPSPs. When slices were bathed in Mg2+-free medium, the amplitude of the EPSP increased substantially. Under these conditions APV reduced the size of the EPSP to that observed with APV in the presence of 1 mM Mg2+. The voltage sensitivities of the APV-sensitive and APV insensitive components of the layer II/III-evoked EPSPs were examined. The APV insensitive component was not voltage dependent and had an extrapolated reversal potential of -10 mV. In contrast, the APV-sensitive component showed an NMDA-like voltage dependency; it was greatest at the most positive potentials tested (-45 mV) and nearly absent at membrane potentials below rest. At potentials near threshold, the APV-sensitive component contributed approximately half of the total response. Although the time to peak and decay were longer for the APV sensitive component, the latency was the same as that of the APV-insensitive component. These results provide evidence that the layer II/III to V pathway, which comprises a major interlaminar circuit in cortex, is mediated directly through NMDA as well as non-NMDA receptors located on the layer V cells. This finding has implications for the role of this circuit in cortical visual plasticity. PMID- 2902204 TI - Methodology and dosimetry in adrenal medullary imaging with iodine-131 MIBG. AB - Iodine-131 MIBG scans were performed in 59 patients in order to localize intra- or extra-adrenal pheochromocytomas (pheos), or to visualize hyperplastic adrenal medulla. Images were obtained from the pelvis to the base of the skull on Days 1, 4, and 7 after tracer injection. The 15 patients with histopathologic confirmation of adrenal medullary disease had positive scans. In three of these, the pheos were visible only on images obtained on Day 7. One scan was false negative. After excluding patients with a predisposition to adrenal medullary disease, nine subjects (28%) without verification of pheo displayed adrenal uptake of the radionuclide. Late images produce a low rate of false-negative scans; the background activity diminishes and even small pheos can be detected. In order to increase the quality of late images, 40 MBq [131I]MIBG was used instead of 20 MBq. The dosimetric considerations are discussed. PMID- 2902205 TI - An adolescent with intermittent headache, transient hemiparesis, and urinary abnormalities. PMID- 2902206 TI - Intraabdominal testis with yolk sac tumor in a 2-year-old child. AB - A case of a large yolk sac tumor in an undescended testicle in a 2-year-old child is presented. No such similar finding has been reported in a young child. Despite the large size of the primary tumor, the high level of serum alpha-fetoprotein and the relatively late clinical presentation, this was a stage I lesion, and the child responded to surgical resection of the tumor and chemotherapy. PMID- 2902207 TI - Studies on improved corneal permeability to bunazosin. AB - Various factors influencing corneal permeability to bunazosin were investigated. The permeability of the cornea to bunazosin increased with increasing pH, either in the presence or absence of caprylic acid; the permeability to bunazosin and the partition of bunazosin were both enhanced by caprylic acid and both enhancements became maximal when the molar ratio of bunazosin: caprylic acid became unity; the permeability to methylparaben, a non-ionic permeant, was not increased by caprylic acid or capric acid and the permeability was not increased by the pretreatment of the cornea with caprylic acid. Furthermore, protein bunazosin interaction was not affected by caprylic acid. The present results suggest that the enhancement of permeability caused by caprylic acid is attributable only to the increased partition of bunazosin to the corneal membrane. PMID- 2902208 TI - Production of leukotrienes from mouse peritoneal macrophages by treatment with a neutral subfraction of bakers' yeast mannan. AB - We concluded that a neutral subfraction of mannan from bakers' yeast (Saccharomyces cerevisiae wild type strain), abbreviated as WNM, was able to induce the release of leukotrienes from mouse peritoneal macrophages (M phi). The culture supernatant fluid of M phi from normal mice cultured with WNM caused a marked contraction of guinea pig ileum. This activity was inhibited by pretreatment of M phi with inhibitor of phospholipase A2 or lipoxygenase before M phi were treated with WNM, and by treatment of the incubation bath with a slow reacting substance antagonist, FPL55712. On the other hand, pretreatment of M phi with a cyclooxygenase inhibitor potentiated contractile response of ileum by culture supernatant fluid of M phi. A high performance liquid chromatographic analysis of a culture supernatant fluid of M phi treated with WNM demonstrated the presence of leukotrienes C4 and D4, and their related compounds. PMID- 2902209 TI - Evidence for heterogeneity between pre- and postjunctional alpha-2 adrenoceptors using 9-substituted 3-benzazepines. AB - A series of alpha adrenoceptor antagonists, including both reference compounds and the novel benzazepine antagonists, SK&F 86466 (6-chloro-2,3,4,5-tetrahydro-3 methyl-1H-3-benzazepine) and two of its 9-substituted derivatives, SK&F 101253 and SK&F 104078, were tested in vitro for affinity at central and peripheral alpha adrenoceptor subtypes. Peripheral alpha-1 adrenoceptor antagonist potency of these agents, as assessed by the receptor dissociation constant (KB) against norepinephrine-induced contraction in the rabbit aorta, correlated with the Ki value for inhibition of [3H]prazosin binding to central alpha-1 adrenoceptors in rat brain homogenates. Central alpha-2 adrenoceptor affinity, measured as the Ki for inhibition of [3H]rauwolscine binding to rat brain homogenates, correlated well with antagonist activity at peripheral postjunctional alpha-2 adrenoceptors as reflected by the KB against B-HT 920-induced contraction in canine saphenous vein. The 9-substituted benzazepines, SK&F 101253 and SK&F 104078, produce preferential blockade of postjunctional vs. prejunctional alpha-2 adrenoceptors in peripheral models. The high affinity of SK&F 104078 for postjunctional alpha-2 adrenoceptors in the canine saphenous vein was confirmed by its ability to inhibit [3H]rauwolscine binding to postjunctional alpha-2 adrenoceptors in this tissue. The observation that the Ki values for these antagonists against [3H] rauwolscine binding correlate with their KB values at the postjunctional alpha-2 adrenoceptors, rather than those at the prejunctional neuroinhibitory alpha-2 adrenoceptor, suggests a pharmacologic similarity between the postjunctional vascular alpha-2 adrenoceptors and the central [3H]rauwolscine binding site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902210 TI - Characterization of hydrolysis of [leu]enkephalin and D-ala2-[L-leu]enkephalin in rat plasma. AB - Based on differences in total metabolite accumulation in the presence or absence of selective peptidase inhibitors, rat plasma is found to have its own unique pattern of enkephalin hydrolysis. Approximately 85-90% of the hydrolysis of [leu]enkephalin is attributed to the combined action of aminopeptidase M and angiotensin converting enzyme, whereas "enkephalinase" and aminopeptidase MII activity against [leu]enkephalin are not detectable. Similarly, 80-90% of the hydrolysis of D-ala2-[L-leu] enkephalin (DALLE) is due to the combined action of aminopeptidase M and angiotensin converting enzyme, whereas aminopeptidase MII and enkephalinase activity against this substrate also could not be detected. This is in contrast to the high susceptibility to hydrolysis by enkephalinase, and the low susceptibility to aminopeptidase activity, for DALLE in brain tissue. Among other alternatives, it is suggested that enkephalin hydrolysis in plasma may appear to be unique because of differences in enzyme conformation and/or the availability of a substance(s) that competes with, or alters the binding of, [leu] enkephalin, DALLE or the inhibitors to the enzymes. PMID- 2902211 TI - Selective vulnerability of glutathione metabolism and cellular defense mechanisms in rat striatum to manganese. AB - The present findings provide experimental evidence for the hypothesis that compromised cellular defense mechanisms, i.e., glutathione (GSH), GSH-peroxidase and catalase in the brain may be involved in neuronal degeneration caused by manganese (Mn) neurotoxicity. Moreover, data are presented demonstrating that the striatum is particularly susceptible to the deleterious effects of Mn. Specifically, exposure to subchronic MnCl2 produced significant reductions in GSH peroxidase activity in the cytosol and mitochondrial fractions of the whole brain and the striatum. The decrease in GSH-peroxidase was most pronounced in the mitochondrial fraction of the striatum where the activity was reduced to 35% of the control. Catalase activity was also decreased in the striatum of rats treated with Mn but not in the whole brain. GSH content was markedly depleted (20% of the control) in the striatum, although only modestly decreased in whole brain (80% of the control). The alterations in the above parameters were accompanied by depletion of dopamine and dopamine metabolites in the striatum. The treatment of rats with Mn also decreased the activity of oxidized glutathione-reductase; the same treatment increased the activity of gamma-glutamyltranspeptidase. The activity of gamma-glutamylcysteine synthetase was not altered by Mn. The possible relevancy of the findings of this study to understanding the mechanism of Mn neurotoxicity of dopamine systems is discussed. PMID- 2902212 TI - Phorbol ester-induced modulation of agonist binding to alpha-1 adrenergic receptors in bovine aortic membranes. AB - Effects of the protein kinase C-activating phorbol ester, phorbol dibutyrate (PDBu) on the binding behavior of the alpha-1 adrenergic receptor were determined from radioligand binding assays at 25 and 2 degrees C. Membranes prepared from PDBu-treated bovine aorta exhibited a 16% reduction in [3H]prazosin binding capacity, whereas [3H]prazosin affinity was unchanged. This may reflect a role for protein kinase C-mediated receptor phosphorylation in determining receptor turnover and surface density. After PDBu treatment, the affinity of epinephrine for [3H]prazosin sites was altered in two respects. Control membranes exhibited both high and low affinity epinephrine binding (KDH, 20 nM; KDL, 1086 nM) whereas, PDBu-treated membranes exhibited only a single class of low affinity sites (KDL, 655 nM). The inclusion of 5'-guanylylimidodiphosphate caused the loss of high affinity sites in control membranes but had no effect on PDBu-treated membranes (KDL, 681 nM). Thus, protein kinase C blocks the ability of the agonist receptor complex to couple to a GTP binding regulatory protein. In binding studies conducted at 2 degrees C epinephrine also bound to high (KDH, 34 nM) and low affinity (KDL, 1920 nM) sites although the percentage of high affinity sites was higher (percentage of RH, 80) than at 25 degrees C (percentage of RH, 19). PDBu-treated membranes also exhibited two agonist affinity states in 2 degrees C studies although affinity was slightly reduced (KDH, 74 nM; KDL, 2405 nM). 5' Guanylylimidodiphosphate was without effect at 2 degrees C. These results indicate that a high affinity agonist binding state can still be achieved after PDBu treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902213 TI - LY 83583 interferes with the release of endothelium-derived relaxing factor and inhibits soluble guanylate cyclase. AB - LY 83583 (6-anilino-5,8-quinolinedione) has been reported to lower intracellular cyclic GMP by an unknown mechanism. The objective of the present study was to investigate the effect of LY 83583 on different types of vasorelaxation and to study its mechanism of action. Low concentrations of LY 83583 (less than or equal to 0.1 microM) inhibited endothelium-dependent relaxations of rabbit aortic strips induced by acetylcholine or by the calcium ionophore A23187. Higher concentrations (greater than or equal to 0.3 microM) were required to produce partial inhibition of relaxation to sodium nitroprusside and glyceryl trinitrate. Cyclic AMP-mediated relaxations, induced by isoprenaline or forskolin, were not affected by LY 83583 (10 microM). The site of interference of LY 83583 with endothelium-dependent relaxation was examined with endothelium-derived relaxing factor (EDRF) released from cultured endothelial cells that were grown on microcarrier beads and stimulated by superfusion with ATP or thimerosal. EDRF in the superfusate was detected by endothelium-denuded segments of rabbit femoral artery, which responded with dilation and, simultaneously, by purified soluble guanylate cyclase (GC) in test tubes, which was activated by EDRF. When LY 83583 was added to the glutathione-containing GC-assay or to the superfusate from cultured endothelial cells, it did not affect stimulation of soluble GC by EDRF but it slowly reversed the dilator response of the arterial detector segment. Superfusion of cultured endothelial cells with LY 83583 (1 microM), rapidly and reversibly inhibited EDRF release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902214 TI - Characteristics of somatostatin desensitization in the pituitary tumor cell line AtT-20. AB - The molecular mechanisms of somatostatin (SRIF) desensitization were investigated in the anterior pituitary tumor cell line AtT-20. Previous studies have shown that pretreatment of AtT-20 cells with SRIF analogs desensitizes the cells to SRIF inhibition of hormone release, cyclic AMP formation and calcium influx. This desensitization may involve a change in the properties of the SRIF receptors. Pretreatment of AtT-20 cells with Trp8-SRIF reduced the binding of the SRIF analog [125I]CGP 23996 (des-Alal, Gly2-[desamino-Cys3, Tyr11]-3, 14 dicarbasomatostatin) to AtT-20 cell membranes. The loss of [125I]CGP 23996 binding was dependent on the time of Trp8-SRIF treatment and was reversible. The ability of GTP analogs to inhibit [125I]CGP 23996 binding was reduced after Trp8 SRIF treatment, suggesting that the SRIF receptor and the inhibitory G proteins become uncoupled during desensitization. This is indicated further by the decrease in SRIF stimulation of GTPase activity and SRIF inhibition of forskolin stimulated adenylyl cyclase activity in desensitized membranes. The reduction and recovery of SRIF inhibition of adenylyl cyclase activity after Trp8-SRIF pretreatment has a similar time course as the changes in [125I]CGP 23996 binding. GTP inhibition of forskolin-stimulated adenylyl cyclase activity is also reduced in SRIF-desensitized membranes. The loss of the GTP effect occurs rapidly and does not fully recover after Trp8-SRIF pretreatment. The levels of ADP ribosylation of inhibitory GTP binding protein, the relative quantity of the alpha subunits of the inhibitory G proteins and their electrophoretic mobility after 2-dimensional gel electrophoretic analysis, are not altered in SRIF desensitized membranes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902215 TI - Role of endogenous dopamine in the central serotonergic deficits induced by 3,4 methylenedioxymethamphetamine. AB - Similar to other amphetamine analogs 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"), a currently popular illicit drug, has been characterized recently as a serotonergic neurotoxin due to its ability to cause long-lasting deficits in markers of central serotonergic function in animals. Because the serotonergic toxicity associated with the MDMA analog methamphetamine has been linked previously to endogenous dopamine and because MDMA, like methamphetamine, elicits pronounced dopamine release in vitro, we have examined the role of endogenous dopamine in both the immediate (3 hr) and longer-term (3 days) central serotonergic deficits induced by systemic MDMA administration to rats. Depletion of central dopamine content with alpha-methyl-p-tyrosine or reserpine, or selective destruction of nigrostriatal dopamine projections with bilateral 6 hydroxydopamine-induced substantia nigral lesions, partially blocked the immediate MDMA-induced reduction in rat striatal tryptophan hydroxylase (TPH) activity. In addition, the longer-term TPH deficits caused by a high single dose of MDMA were completely prevented by prior alpha-methyl-p-tyrosine or reserpine, and attenuated significantly by inhibition of dopamine uptake with the selective dopamine-uptake blocker GBR 12909. These results implicate endogenous drug released dopamine as a partial mediator of the initial decrease in TPH activity caused by MDMA and as an important prerequisite to the development of long-term MDMA-induced neurotoxicity. Potential mechanisms of dopamine-mediated toxicity are discussed. PMID- 2902216 TI - Characterization and function of bradykinin receptors in vascular endothelial cells. AB - One of many important roles of the naturally occurring nonapeptide bradykinin (BK) is the modulation of vascular tone. As endothelial cells may play vital roles in the physiology of vascular tissues, it is important to understand the interaction of this peptide with endothelial cells. By using radiolabeled BK we have demonstrated for the first time BK specific binding sites in membranes of bovine pulmonary artery endothelial cells. There are two types of receptors shown in binding assay: one with a saturable, high-affinity binding (Kd = 1.28 +/- 0.21 nM, maximum binding = 111.4 +/- 12.0 fmol/mg) and the other with not readily saturable, low-affinity binding. The activation of BK receptors on bovine pulmonary artery endothelial cells is assessed by two functional assays, namely, the release of endothelium-derived relaxing factor and the elevation of cytosolic calcium. The characteristics of the BK receptors in both binding and functional assays indicate that the high-affinity binding is to B2 receptors and the low affinity binding is to B1 receptors on the cells. Thus, high-affinity binding is blocked by B2 antagonists, D-Arg[Hyp3, thienylalanine5,8,D-Phe7]-BK and [thienylalanine5,8, D-Phe7]-BK and low-affinity binding is blocked by B1 antagonist des-Arg9[Leu8]-BK. The elevation of intracellular calcium and the release of endothelium-derived relaxing factor in response to BK in endothelial cells is predominately through B2 receptor activation. The ability to subtype BK receptors in endothelial cells may facilitate the understanding of the vascular functions of BK and the potential design of drugs to regulate these functions. PMID- 2902217 TI - The effect of potassium on exocytosis of transmitter at the frog neuromuscular junction. AB - 1. Electrophysiology and morphology have been combined to investigate the time course of the exocytosis of quanta of neurotransmitter induced by elevated concentrations of K+ at the frog neuromuscular junction. 2. Replicas of freeze fractured resting nerve terminals fixed in the presence of 20 mM-K+ showed images of fusion of synaptic vesicles with the presynaptic axolemma which were closely associated with the active zones. After 1 min in 20 nM-K+ fusions appeared also outside the active zones, and by 5 min they became uniformly distributed over the presynaptic membrane. 3. The average total density of fusions was not significantly different at the various times examined since it decreased at the active zones while it increased over the rest of the membrane. 4. Resting terminals fixed in 20 mM-K+ released 33,000-45,000 quanta after the addition of fixative; terminals stimulated by 20 mM-K+ for 1-5 min released 50,000-100,000 quanta during fixation. The fixative potentiated K+-induced transmitter release. 5. Fusions were uniformly distributed in terminals pre-incubated for 5 min in 20 mM-K+ without added Ca2+, stimulated by adding Ca2+ for 30 s, and then fixed. Conversely, after 5 min stimulation in hypertonic Ringer solution fusions remained predominantly located near the active zones. A similar distribution was observed after 15 min stimulation by a lower concentration of K+ (15 mM). 6. At all concentrations of K+ tested (10, 15, 20, 25 mM) miniature end-plate potential (MEPP) rate attained a steady-state value within 10-15 min. Values from a single junction were generally lower at higher concentrations of K+, which indicates partial inactivation of the secretion-recycling process. 7. The data indicate that K+ initially activates exocytosis at the active zones. Subsequently, ectopic exocytosis is activated while sites at the active zones appear to undergo partial inactivation. These phenomena are not related to the intensity or to the amount of previous secretion. PMID- 2902218 TI - Extrinsic and intrinsic neural control of pyloric sphincter pressure in the dog. AB - 1. In chloralose-urethane-anaesthetized dogs a manometric assembly was inserted via a gastrostomy to monitor pyloric pressure with a sleeve sensor. Antral and duodenal contractions were monitored with both manometric side holes and serosal strain gauges. 2. Subserosal silver wire electrodes were placed in the antrum 5 cm orad and the duodenum 3 cm aborad to the pylorus to facilitate field stimulation of intramural nerves. 3. The pylorus exerted spontaneous tone (10.8 +/- 4.8 mmHg) with phasic contractions occurring at a rate varying from 1-5 min-1 and, at times, with a superimposed higher frequency up to 15 min-1. Atropine (30 micrograms kg-1 I.V. and 10 micrograms I.A.) reduced and tetrodotoxin (50-100 micrograms I.A.) enhanced the phasic activity significantly. 4. Bilateral cervical vagal section had no consistent influence on pyloric motility. 5. Stimulation of the distal ends of the cervical vagal nerves at low frequencies (0.2-0.5 Hz, 1-3 ms, 20 V) induced phasic pyloric contractions, which were abolished by atropine or hexamethonium (10 mg kg-1 I.V. and 1 mg I.A.). Higher frequencies (greater than 0.7 Hz) of stimulation inhibited both phasic and tonic contractions and this inhibition was unaffected by atropine, hexamethonium, phentolamine (1.5 mg kg-1 I.V. and 100 micrograms I.A.) or propranolol (1 mg kg-1 I.V. and 100 micrograms I.A.). All neural responses were blocked by tetrodotoxin (50-100 micrograms I.A.). 6. Duodenal field stimulation (0.2-5 Hz, 0.5 ms, 40 V) induced strong phasic and tonic contractions in the pylorus. This excitation was blocked by atropine, hexamethonium, tetrodotoxin (50-100 micrograms I.A.) or duodenal transection orad to the stimulating electrodes. 7. Antral field stimulation (0.5-1 Hz, 0.5 ms, 40 V) completely abolished phasic activity in the pylorus and reduced tonic activity, regardless of whether the contractile activity was spontaneous or induced by neural stimulation. This inhibitory action was unaffected by atropine, hexamethonium or propranolol but was blocked by tetrodotoxin and antral transection aborad to the stimulating electrodes. Phentolamine attenuated the inhibitory effect of antral field stimulation on pyloric motility. 8. It is concluded that the distal canine pylorus exhibits myogenic tone and phasic activity which is modulated by extrinsic and intrinsic nerve pathways. Vagal nerves contain fibres, activated by different stimulus parameters which can either excite or inhibit pyloric activity. Activation of antral nerves inhibits pyloric activity, with both non-adrenergic, non cholinergic and phentolamine-sensitive pathways contributing to this inhibitory response.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2902219 TI - Prolonged nerve stimulation causes changes in transmitter release at the frog neuromuscular junction. AB - 1. Synaptic transmission in the two cutaneus pectoris muscles of frog was compared after prolonged unilateral nerve stem stimulation in vivo via surface electrodes. 2. In Mg2+-blocked preparations at 2 Hz stimulation the mean number of quanta released per impulse (m) was significantly lower in the stimulated muscles. On average, m was reduced to 53% (range 31-74%) of the values in control muscles. 3. Similarly, in curare-blocked preparations end-plate potential (EPP) amplitudes in the stimulated muscles were reduced to 30-92% (average 63%) of the control values, while no differences in muscle fibre diameter and resting potential were detectable. 4. In most muscles plateau values after tetanic stimulation at 40 Hz for 2 s were also smaller in the stimulated muscles. Compared to the first EPP in the train, however, plateau values were less depressed in stimulated than in unstimulated muscles. Also facilitation, i.e. the amplitude ratio of the largest versus the first EPP was more pronounced in stimulated muscles. 5. No effects of stimulation were noticed in four winter frogs, in which transmitter release is depressed due to seasonal factors. 6. It is concluded that prolonged nerve stimulation can cause under certain conditions profound depression of transmitter release with changes in facilitation and depression. PMID- 2902221 TI - Time course of transmitter action at the sympathetic neuroeffector junction in rodent vascular and non-vascular smooth muscle. AB - 1. Transmitter release from sympathetic postganglionic nerve terminals innervating the guinea-pig and mouse vas deferens and the rat tail artery has been studied in vitro by focal extracellular recording with particular emphasis on the time course of transmitter action underlying the intracellular potential changes. 2. In the absence of stimulation, spontaneous excitatory junction currents (SEJCs) were recorded with amplitudes up to 500 microV and durations between 40 and 100 ms. SEJCs were unaffected by the competitive alpha adrenoceptor antagonist prazosin but blocked by alpha, beta-methylene ATP which desensitizes P2-purinoceptors. 3. During trains of supramaximal stimuli at 0.1-4 Hz stimulus locked excitatory junction currents (EJCs) were evoked intermittently from the population of varicosities located under the suction electrode. 4. SEJCs were similar in amplitude and time course to EJCs evoked by low-frequency stimulation in the same attachment in all three tissues. 5. SEJCs recorded using either a conventional AC amplifier or a patch clamp amplifier had the same time course. 6. These studies show that the time course of the current underlying the excitatory junction potential is brief and essentially the same in three different tissues. The prolonged time course of the excitatory junction potential in different tissues can be accounted for by the passive membrane properties. PMID- 2902220 TI - Quantal secretion at release sites of nerve terminals in toad (Bufo marinus) muscle during formation of topographical maps. AB - 1. The number of quanta secreted from selected sites along terminal branches at suppressed synapses in the developing toad (Bufo marinus) gluteus muscle has been determined. The topographical projection from segmental nerves 8 and 9 to the ventral surface of this muscle matures slowly as toads develop in size from 12 to 40 g. Terminal branches of nerves 8 and 9 were visualized by prior staining with the fluorescent dye, 3-3-diethyloxardicarbocyanine iodide (DiOC2(5]. 2. The evoked quantal release recorded with an extracellular electrode (m(e) at different positions along the length of terminal branches at synaptic sites innervated either by nerve 8 (me,8) or nerve 9 (me,9) was determined in an external Ca2+ concentration, [Ca2+]o, of 0.35-0.45 mM. For over 90% of branches longer than 80 microns, me declined along exponential curves from a relatively large value at the proximal end of branches for both nerve 8 and nerve 9 terminals; the exponent for these exponential curves gave quantal length constants that varied from 26 to 80 microns (48 +/- 4 microns, mean +/- S.E.M.) depending on the length of the branch. 3. The evoked quantal release recorded with an intracellular electrode (m) at synaptic sites dually innervated by nerve 8 and nerve 9 was nearly always (greater than 90%) greater for nerve 8 terminals than for nerve 9 terminals. At singly innervated sites the value of m per 100 microns length of terminal declined approximately exponentially with an increase in total terminal length (length constant 400 microns). However, at dually innervated sites the value of m per 100 microns length of nerve 9 terminal was very low at all total terminal lengths compared with singly innervated sites; this indicates that nerve 9 terminals were suppressed at dually innervated sites. 4. At five dually innervated sites, seven out of nine terminal branches of nerve 8 showed an exponential decline in me,8 along their length, from a relatively large value near the proximal end of the branches (length constant 35 +/- 3 microns, mean +/- S.E.M.). In contrast, all the terminal branches of nerve 9 greater than 80 microns showed a uniformly low value of me,9 along their length. 5. It is suggested that the suppression of nerve 9 terminals at dually innervated sites is primarily due to a decrease in the probability of secretion of normally highly secreting release sites at the proximal end of terminal branches. PMID- 2902222 TI - Flexion characteristics of fixed partial denture frameworks tested by using elapsed-time holographic interferometry. PMID- 2902223 TI - Sulfasalazine in juvenile rheumatoid arthritis. PMID- 2902224 TI - Restriction fragment length polymorphism of T cell receptor alpha and beta chain genes in patients with ankylosing spondylitis. AB - Ankylosing spondylitis (AS) is very strongly associated with the class I major histocompatibility (MHC) antigen HLA-B27. Because class I MHC antigens function as restricting elements recognized by T cell antigen receptors, we sought to determine if there is preferential association between AS and particular T cell (TcR) alleles. In 49 patients with AS and 23 controls, we determined the frequencies of restriction fragment length polymorphisms linked to genes encoding the TcR alpha and beta chain constant regions. There was no significant difference between patients with AS and controls with respect to the frequencies of possible TcR genotypes. Although T cells may play a role in the pathogenesis of AS, these results provide no evidence for a distinctive germline T cell repertoire associated with AS. PMID- 2902225 TI - Association between ankylosing spondylitis and a 9.2 kb Pvu II class I HLA DNA restriction fragment: a reassessment. AB - Recently, McDaniel, et al (Arthritis Rheum 1987;30:894) reported a statistically significant association between ankylosing spondylitis (AS) and the presence in Pvu II digested genomic DNA of a 9.2 kb restriction fragment hybridizing with an HLA-B7 cDNA probe. The fragment was found in 35 of 48 unrelated HLA-B27+ Caucasian patients with primary AS and in 25 of 107 controls. We report finding this restriction fragment in only 10 of 33 such patients and in 17 of 41 controls. We are thus unable to confirm an association between AS and the restriction fragment identified by McDaniel, et al. PMID- 2902226 TI - 2-Phenylpyrroles as conformationally restricted benzamide analogues. A new class of potential antipsychotics. 2. AB - A series of 2-phenylpyrrole Mannich bases was synthesized and screened in pharmacological models for antipsychotic activity and extrapyramidal effects. Structure modifications of 5-(4-fluorophenyl)-2-[[4-(2-methoxyphenyl)-1 piperazinyl]methyl]pyrrole (1), the prototype of a new class of sodium independent atypical dopamine D-2 antagonists, resulted in 2-[[4-(7-benzofuranyl) 1-piperazinyl]methyl]-5-(4-fluorophenyl)pyrrole (15), which was an even more potent and selective D-2 antagonist than the parent compound. The excellent oral activity in the apomorphine-induced climbing behavior and the conditioned avoidance response tests and the absence of catalepsy make this compound particularly promising as a potential antipsychotic with a low propensity to induce acute extrapyramidal side effects. PMID- 2902227 TI - Serotonergic properties of spiroxatrine enantiomers. AB - The neuroleptic drug spiperone (1) has proven very useful in the characterization of putative serotonin (5-hydroxytryptamine, 5-HT) receptors. Thus, 5-HT1 receptors have been divided into subtypes based on their affinities for 1: 5-HT1A sites have high affinity, while 5-HT1B sites have low affinity. However, the usefulness of 1 for the pharmacological characterization of 5-HT1A sites is limited because of its high affinity for 5-HT2 (as well as D2-dopaminergic) receptors. A close analogue of 1, (+/-)-spiroxatrine (2), has much higher affinity for 5-HT1A receptors and much lower affinity for 5-HT2 receptors. We report here the stereospecific synthesis of (R)-(+)- and (S)-(-)-spiroxatrine enantiomers and their evaluation at several 5-HT receptors and D2-dopaminergic and alpha 1-adrenergic receptors. PMID- 2902228 TI - Molecular approaches to dysmorphology. AB - The biochemical and physiological defects underlying human dysmorphic syndromes can now be approached using techniques of molecular biology. The genetic component of the causation of the dysmorphology can be studied in isolation from the environmental component by using large, rare families which exhibit the same phenotype as more complex multifactorial disorders, but inherit the mutation in a monogenic fashion. Such an analysis starts with the determination of linkage to a gene probe, followed by the use of newer techniques of molecular biology to enable cloning and sequencing of the mutated gene. Analysis of the gene product by amino acid sequence homology to other known proteins, and tissue specific expression, may place the defect within the cascade of events associated with development and differentiation. Once cloned, the gene can also be manipulated in transgenic laboratory animals and the effect of its mutation studied directly. The use of techniques of molecular biology to study the genetic aspects of dysmorphic syndromes will allow insight to be gained both into normal fetal development and into the causes of congenital malformations. PMID- 2902230 TI - Psychiatric drugs and inhibited female orgasm. AB - The available evidence concerning sexual side effects of psychiatric drugs suggests that inhibited female orgasm may be associated with the use of hetereocyclic antidepressants, monoamine oxidase inhibitors, benzodiazepines, and neuroleptics. Possible mechanisms of action including anticholinergic, alpha adrenergic blockade, and serotonergic effects are discussed. PMID- 2902229 TI - Structural and segregation analysis of the type II collagen gene (COL2A1) in some heritable chondrodysplasias. AB - Seventy-seven persons with a variety of heritable chondrodysplasias were screened for gross rearrangements of the structural gene encoding the major cartilage collagen, collagen II. None was found. Segregation of the locus (COL2A1) was studied in 19 pedigrees using three restriction site dimorphisms (shown by PvuII, HindIII, and BamHI) and a length polymorphism as linkage markers. Discordant segregation between COL2A1 and the mutant locus was seen in pedigrees with multiple epiphyseal dysplasia, autosomal recessive spondyloepiphyseal dysplasia tarda, hypochondroplasia, pseudoachondroplasia, diaphyseal aclasis, and trichorhinophalangeal syndrome. One pedigree with diastrophic dysplasia was weakly concordant. Autosomal dominant spondyloepiphyseal dysplasia tarda and metaphyseal chondrodysplasia (type Schmid) were not informative. We conclude that mutations of the collagen II gene are not a common feature of the heritable chondrodysplasias. Since the chondrocyte binding protein, chondrocalcin, is also encoded at COL2A1 our conclusions apply equally to this gene. PMID- 2902231 TI - Differential modulation of glutamate metabolizing enzymes in mouse and chick cultured glial cells by insulin. AB - The effect of physiological concentrations of insulin (2 and 20 ng/ml) on glutamine synthetase (GS) and glutamate dehydrogenase (GDH) activities were compared in mouse and chick glial cells in culture. Addition of insulin to serum containing medium increased the level of GS and GDH activities in glial cells prepared from 14-15-day-old embryonic mice. A similar but less pronounced effect was observed with glia derived from newborn mouse brain. In absence of serum, addition of insulin had no effect on the tested enzymes. The effects of insulin on enzymatic activities of glial cells from 14-15-day-old embryonic chick brain hemispheres were, in contrast, quite different. A significant decrease of GS activity was induced by the hormone, only in the absence of serum. Conversely, the presence of serum enhanced an inhibitory effect of insulin toward chick GDH. The different effects of insulin and the different serum dependence observed for the mammalian and the avian model could reflect fundamental chemical differences between both species as indicated by immunoelectrophoretic analysis. However, it can be concluded that insulin may be a physiological factor regulating glial maturation and amino acid neurotransmitter metabolism in the central nervous system. PMID- 2902232 TI - Tyrosine hydroxylase and serotonin containing cells in embryonic rat rhombencephalon: a whole-mount immunocytochemical study. AB - Rhombencephala from rat embryos were processed as whole-mounts for immunocytochemical detection of monoaminergic cell populations, using antibodies to tyrosine hydroxylase (TH) and serotonin (5-HT). Specific advantages of the whole-mount technique over the classical serial-section method were that even isolated immunoreactive (IR) cells could be detected easily, and three dimensional relationships could be ascertained without the need for serial reconstruction. Embryos between embryonic days (E) 12 and 16 (the day following nocturnal mating being considered as E1) were used in this study. Both TH and 5 HT immunoreactivities were already detectable at E12, even in the smallest embryos (crown-rump length: 6 mm), but there was a striking difference in the number and regional distribution of these two types of IR cells. TH was expressed in several cell groups located in the rostral rhombencephalon (the presumed anlage of the A4-7 complex) as well as in the caudal rhombencephalon (the presumed anlagen of groups A1-2 and C1-3), whereas 5-HT was expressed in very few cells located near the rostral border of the rhombencephalon (presumed anlage of the B4-9 complex). Although the three-dimensional distribution of the TH-IR cell groups underwent some modifications during the period studied, its general pattern remained relatively stable after E12. This contrasted with the sequential appearance of the 5-HT-IR cell groups and their spatial transformations during this period. Using the rhombencephalic isthmus as a landmark, we found that conspicuous 5-HT-IR fibre bundles penetrated into the mesencephalon from E13 onwards, but that the 5-HT IR cell bodies were exclusively located caudal to the borderline between the mesencephalon and the rhombencephalon (the rhombencephalic isthmus). We therefore suggest the term "rostral rhombencephalic raphe nuclei" for the rostral 5-HT cell groups instead of "mesencephalic raphe nuclei," which is a misnomer. Close spatial association between TH and 5-HT-IR elements was observed mainly in the caudal rhombencephalon, where 5-HT-IR fibres coursed through an area containing numerous TH-IR cell bodies (the presumed anlagen of groups A1-2 and C1-3). PMID- 2902233 TI - Fim-1, Fim-2/c-fms, and Fim-3, three common integration sites of Friend murine leukemia virus in myeloblastic leukemias, map to mouse chromosomes 13, 18, and 3, respectively. AB - Three common proviral integration sites, Fim-1, Fim-2/c-fms, and Fim-3, have been described in mouse myeloid leukemias induced by the Friend murine leukemia virus. The nature and function of Fim-1 and Fim-3 are still unknown since no transcript from these loci has been detected so far. To identify these two loci, we undertook their chromosomal localization using restriction fragment length polymorphism detected between C57BL/6 mice and the wild-derived inbred strain of Mus spretus. Using interspecific backcross analysis, we mapped Fim-1 to mouse chromosome 13 and Fim-3 to mouse chromosome 3. Interestingly, Fim-3 is tightly linked to Evi-1, another common integration site of ecotropic virus involved in another model of mouse myeloid leukemogenesis. Fim-2 spans the 5' end of the c fms gene, which encodes for the macrophage-colony-stimulating factor receptor. We located the c-fms gene on the D band of chromosome 18 by in situ hybridization. PMID- 2902235 TI - Adherence of bacteria to human foreskins. AB - The mucosal surface of the human foreskin from newborns shows a propensity to be colonized by pathogenic bacteria. Bacteria with P fimbriae and type 1 fimbriae adhere. However, hydrophobic interaction as well as electrostatic charge appear to be as important in this adherence as are fimbriae. Since bacterial adherence has been shown to precede urinary tract infection in female patients it is assumed that this adherence to the foreskin in male patients also may be necessary before initiation of the disease. The high incidence of urinary tract infection in uncircumcised male patients combined with these findings of adherence of pathogenic bacteria to the mucosal surface of the foreskin, thus, would seem to be related. Prevention of urinary tract infection and acute pyelonephritis in male neonates then may require either circumcision or the prevention of bacterial adherence to the human foreskin. PMID- 2902234 TI - Genetic mapping of the Mx influenza virus resistance gene within the region of mouse chromosome 16 that is homologous to human chromosome 21. AB - A total of 318 progeny from four backcrosses involving different laboratory strains and subspecies of Mus musculus were analyzed to map the Mx gene to the region of mouse chromosome 16 (MMU 16) which is homologous to human chromosome 21 (HSA 21). This result suggests that Mx will be found in the region of HSA 21 which has been implicated in Down syndrome when inherited in three copies. PMID- 2902236 TI - Brucella suis biotype 4: a case of granulomatous nephritis in a barren ground caribou (Rangifer tarandus groenlandicus L.) with a review of the distribution of rangiferine brucellosis in Canada. AB - Severe granulomatous nephritis caused by Brucella suis biotype 4 was found in a barren ground caribou (Rangifer tarandus groenlandicus) from Northwest Territories, Canada. A review of the distribution of human and animal cases of brucellosis in northern Canada indicated that B. suis biotype 4 is distributed widely and is probably enzootic in most Canadian caribou herds. PMID- 2902237 TI - A survey of medication treatment for hyperactive/inattentive students. AB - Since 1971, the Baltimore County Health Department has conducted nine biannual surveys of school nurses in all of the county's public and private schools to determine the prevalence of medication treatment for hyperactivity/inattentiveness among students. The results reveal a consistent doubling of the rate of medication treatment for hyperactive/inattentive students every four to seven years such that in 1987, 5.96% of all public elementary school students were receiving such treatment. Related trends from 1971 to 1987 have been that stimulants increased from 76% to 99% of the medication prescribed; methylphenidate hydrochloride rose from 40% to 93% of the total; the male-female ratio dropped from an average of 8:1 to 5:1; the rate of medication treatment for hyperactive/inattentive students rose faster in secondary than in elementary schools; and 25% of students receiving stimulant medication in 1987 were in special education classes or schools. PMID- 2902238 TI - Evaluation of a new antianginal agent, nipradilol, in effort angina using holter monitoring. AB - The purpose of this study was to investigate the efficacy, effective dose, administration frequency and antianginal effect of a new antianginal agent, nipradilol, in 12 patients with stable effort angina. A single blind design was employed; the test consisted of an observation period (1 week) and a treatment period (1-2 weeks). Twenty four hour Holter monitoring was performed on the penultimate day of each period. Nipradilol was administered twice a day at a daily dose of 3-12 mg (mean 7.9 +/- 3.3 mg). The mean frequency of ST-segment depression was 7.1 +/- 6.7 times per day at baseline and 3.1 +/- 2.7 after drug administration, showing a significant reduction (p less than 0.05). The suppression of ST-segment depression and decrease in heart rate due to this drug persisted for 12 hours following administration. The plasma drug concentration at a daily dose of 12 mg peaked at 9.5 +/- 2.4 ng/ml 1 hour after administration and the 12 hour value was 2.3 +/- 1.2 ng/ml. No side effects were observed. Therefore, it seems that, when administered twice a day (total daily dose 6 mg) this drug is effective in effort angina and that the antianginal effect is mainly attributable to beta-adrenoceptor blockade. PMID- 2902239 TI - [Variations of physiological functions and psychological measures and their relationships on delayed shift of sleeping time]. AB - The variations of sublingual temperature, pulse rate, flicker fusion frequency (CFF), subjective fatigue feelings (SFF) and 8 selected reaction times and the relationships between them were examined in six university students under the condition of successive 6-h delayed shift with 8 sleeping h and 22 waking h for 6 d. SFF was measured by the scales proposed by the Japanese Society for Industrial Fatigue Research. On the 2nd d when the shifting was started after the subjects had slept from 00:00 to 08:00 and on the 3rd d after sleeping h of 06:00 to 14:00, the variations of sublingual temperature, pulse rate and CFF showed a pattern of circadian rhythm. However, on the 4th-5th d the rhythms of sublingual temperature and pulse rate were flattened. On the other hand, CFF demonstrated a variation of having a nearly constant tendency till 08:00, followed by a gradual decrease during the daytime. The variation of SFF (the scale of "sleepiness and dullness") was similar to that of CFF, although the change of the score was in the opposite direction. On the 3rd-4th d, the 4th-5th d and the 6th d, significantly high rank correlations were observed between sublingual temperature and pulse rate and between CFF and SFF. However, between sublingual temperature and CFF, a high correlation which was observed on the 1st and the 2nd d was not seen on the 4th-5th and 6th d. Eight selected reaction times were shortened during the experimental days, but there was no consistent pattern of variation within these days. The results of the experiment showed that the relationship between CFF and SFF exists during the daytime when the arousal level is low. PMID- 2902240 TI - Transitory cardiovascular responses to rapid infusion of blood into aorta of rabbit. AB - Blood (5 to 15 ml) was infused into aorta of the anesthetized rabbit through the carotid artery or femoral artery at a constant rate (0.55 to 8.3 ml/s). The carotid sinuses were occluded. The systemic arterial pressure (SAP) began to rise immediately at the onset of the infusion and dropped gradually in most cases during the infusion. SAP continued to decline after the infusion and in many cases became lower than the preinfusion pressure. Within seconds, SAP tapered off to its lowest point and resumed a gradual rise, leveling off higher than its initial pressure. A depressor effect caused by the rapid infusion of blood into the aorta (DRIA) was observed in every rabbit. DRIA was not suppressed much by the section of aortic or vagal nerves. DRIA was markedly suppressed by the administration of alpha-adrenergic blockade, but beta-adrenergic blockade had little effect on DRIA. By using a hydraulic model of the closed circulatory system, a theoretical analysis was made on the basis of the "theory of active fluid element," a theory developed by Hatakeyama, one of the authors, and it was demonstrated that DRIA must not be considered to be a passive hemodynamic phenomenon. The results obtained suggest that a nervous regulatory mechanism- rather than the reflex via the carotid sinus or aortic baroreceptors, or other mechanoreceptors--plays an important part in the venous and the cardiac regions. PMID- 2902241 TI - Purification of K88 and K99 pili from porcine enterotoxigenic Escherichia coli by affinity chromatography. PMID- 2902243 TI - [Of what importance is nursing in Europe today and tomorrow? Impressions from the European Nursing Conference of the WHO (June 21-24, 1988)]. PMID- 2902242 TI - Effects of aldosterone on NEM-sensitive ATPase in rabbit nephron segments. AB - Aldosterone (aldo) treatment of animals stimulates the rate of H+ secretion in the collecting duct, a process which may involve an H+-ATPase sensitive to inhibition by NEM (N-ethylmaleimide). Therefore, we determined NEM-sensitive ATPase activity in distal nephron segments from three groups of adrenalectomized (adx) rabbits maintained on different doses of aldo (in an osmotic minipump) for seven days. Group 1 was given 1.5 micrograms aldo/100 g body wt/day, whereas groups 2 and 3 were maintained on 5 micrograms and 50 micrograms of aldo/100 g body wt/day, respectively. Aldo concentrations in the plasma of groups 1, 2 and 3 were 10.4 +/- 0.8, 70 +/- 7 and 408 +/- 133 ng/dl, respectively. There was a significant increase in NEM-sensitive ATPase activity in connecting tubule (CNT) and cortical, outer and inner medullary duct segments (CCD, OMCD and IMCD) but not in cortical thick ascending limb (CTAL) and distal convoluted tubule (DCT) in group 2 as compared to group 1. A further increase in plasma concentration of aldo (group 3) did not produce any more increase in NEM-sensitive ATPase activity in the CNT, CCD, OMCD and IMCD, but did increase the enzyme activity in the DCT. These results are consistent with the hypothesis that aldo increases H+ secretion in the connecting tubule and collecting duct segments by increasing the activity of NEM-sensitive H+-ATPase activity in these segments. PMID- 2902244 TI - [European Nursing Association session April 25-27, 1988 in The Hague, Holland]. PMID- 2902245 TI - First trimester prenatal diagnosis of metachromatic leukodystrophy on chorionic villi by 'immunoprecipitation-electrophoresis'. AB - Prenatal diagnosis of metachromatic leukodystrophy (MLD) due to arylsulphatase A (ASA) deficiency can be performed by amniocentesis with the disadvantage of a late pregnancy termination. Whether chorionic villi (CV) obtained by trophoblast biopsy during the first trimester of pregnancy can be useful for diagnosis depends on the reliability of results. The complexity of arylsulphatase expression in CV and the existence of several isozymes make diagnosis difficult. However, the use of an anti-ASA antiserum enabled us to discriminate between ASA and a comigrating contaminant isozyme, and the antigen-antibody (Ag-Ab) complex gave better evidence of the presence or absence of ASA after enhancement of activity with 4-methylumbelliferyl sulphate (4-MUS). We propose that immunoprecipitation followed by electrophoresis could be a valuable method of MLD prenatal diagnosis on chorionic villi. PMID- 2902246 TI - Continuing high lung cancer mortality among ex-amosite asbestos factory workers and a pilot study of individual anti-smoking advice. PMID- 2902247 TI - [Results with intertrochanteric valgus osteotomy in the management of coxarthrosis]. PMID- 2902248 TI - [Distal radio-ulnar joint instability]. PMID- 2902249 TI - [Normal geometric value of the hip joint in adults]. PMID- 2902250 TI - [Bone scintigraphy in the diagnosis of Perthes disease]. PMID- 2902251 TI - [Arthrography of the shoulder joint]. PMID- 2902252 TI - [Free transplantation of the fibula with microvascular anastomosis in the substitution of a 21 cm defect in the tibia]. PMID- 2902254 TI - [Functional study of the shoulder joint]. PMID- 2902253 TI - [Anatomical bases of a latissimus dorsi skin-muscle-bone flap]. PMID- 2902255 TI - [A new surgical method for the management of a herniated muscle caused by venous leg ulcer]. PMID- 2902256 TI - [A case of acromioclavicular dislocation associated with clavicular fracture]. PMID- 2902257 TI - [Simultaneous occurrence of Dupuytren's contracture and atheroma]. PMID- 2902258 TI - Restriction fragment length polymorphism of bcr in Japanese patients with hematological malignancies. AB - We surveyed DNAs from patients with various hematological malignancies by Southern blot hybridization to analyze bcr rearrangements, and detected a new restriction fragment length polymorphism (RFLP) of the breakpoint cluster region at a BamHI site in three patients. By using a 1.2-kb HindIII-BglII 3' bcr probe, unusual BamHI restriction enzyme fragments (1.9 kb and 1.4 kb) were detected from the DNAs of three patients with hematological malignancies. DNAs from cultured fibroblasts derived from the skin of a patient, as well as from peripheral leukocytes of the father of a patient and the mother of another patient, showed identical 1.9- and 1.4-kb additional bands, besides a 3.3-kb germline band, establishing that polymorphism, rather than gene arrangement, was responsible for these additional restriction enzyme fragments. However, RFLP was not detected in the DNAs of 40 normal unrelated individuals. PMID- 2902259 TI - [Treatment of Graves-Basedow disease]. PMID- 2902260 TI - [Physiopathological and clinical aspects of the use of benzodiazepines in the aged]. PMID- 2902261 TI - [A 39-year-old woman, with bilateral ovarian neoplasms, admitted for treatment of hyperglycemia]. PMID- 2902262 TI - [Clostridium perfringens sepsis and hypernephroma]. PMID- 2902263 TI - Trial of high-dose Edmonston-Zagreb measles vaccine in Guinea-Bissau: protective efficacy. AB - In a randomised study of 558 children in an urban African community, the protective effect of the Edmonston-Zagreb (EZ) measles vaccine given in a dose of 40,000 plaque forming units from the age of 4 months was compared with the effects of a standard dose (6000 tissue culture infectious units) of Schwarz measles vaccine given from the age of 9 months. During two years of follow-up, all 14 clinical cases of measles occurred in the Schwarz group; 10 of the children contracted measles before vaccination and 4 after measles vaccination. Thus the EZ vaccine provided significant protection against measles both before and after the usual age of vaccination. Among the children who were exposed to measles at home, those given EZ vaccine were better protected than either unvaccinated children or those given the Schwarz vaccine. PMID- 2902264 TI - Trial of high-dose Edmonston-Zagreb measles vaccine in the Gambia: antibody response and side-effects. AB - In a randomised trial, infants living in a large village in The Gambia were immunised either at 4 months of age with 40,000 plaque forming units (PFU) of the Edmonston-Zagreb (EZ) measles vaccine or at the usual age of 9 months with 6000 TCID50 of a conventional Schwarz measles vaccine. Measles developed in 2 of 119 children who received the EZ vaccine, in 1 before and in the other after 9 months of age. In the Schwarz group measles developed in 7 of 120 children--in 5 before and in 2 after 9 months of age. Serological responses measured at 5 months after vaccination and at 18 months of age were satisfactory in both groups although in the Schwarz group levels were on average 2-fold higher than in the EZ group. The frequencies of fever, cough, vomiting, and diarrhoea were no higher in the EZ vaccinees in the 3 weeks following vaccination than in age-matched non-immunised controls. Long-term morbidity as assessed by clinic attendances and weight at 18 months of age was much the same in the two groups. The EZ measles vaccine is thus safe and clinically and serologically effective when used in a high dose to immunise young Gambian infants. PMID- 2902265 TI - Effect of dry-heating of coagulation factor concentrates at 80 degrees C for 72 hours on transmission of non-A, non-B hepatitis. Study Group of the UK Haemophilia Centre Directors on Surveillance of Virus Transmission by Concentrates. AB - 32 patients with coagulation factor deficiencies and likely to be susceptible to non-A, non-B hepatitis (NANBH) virus infection were treated with a total of 20 batches of a factor VIII concentrate and 10 batches of a factor IX concentrate, both heated at 80 degrees C for 72 h in the freeze-dried state. Serial measurements of serum aminotransferase levels for 4 months revealed no patterns of rises attributable to NANBH. Severe dry heating appears to have reduced the risk of NANBH transmission from about 90% in untreated concentrates to a statistically determined rate of 0-9%. No evidence was found in recipients of infection with hepatitis B or human immunodeficiency virus. PMID- 2902266 TI - Clinical and serological features of human herpesvirus-6 infection in three adults. AB - 3 adult patients with serological evidence of human herpesvirus-6 (HHV-6) infection had mild, afebrile illnesses with nonspecific symptoms. In each case, the characteristic clinical feature was the presence of enlarged, bilateral, non tender, anterior and posterior cervical nodes early in the illness which persisted for up to 3 months. HHV-6 IgG antibody reciprocal titres of 160 to 2560 were found during acute infection, and decreased to a titre of 10 in 1 patient 3 years later. IgM responses were detected at low reciprocal titres (10) in 2 patients and disappeared after several months. PMID- 2902268 TI - Do CD4-positive cytotoxic T cells damage islet beta cells in type 1 diabetes? AB - The mechanism by which islet beta cells are destroyed in type 1 diabetes is still unknown. Because in diabetes the majority of T cells activated in vivo express CD4 and the islet beta cells selectively express the HLA class II antigens needed for recognition by CD4-positive T cells, the possibility that selective damage to islet beta cells may be caused by CD4-positive cytotoxic cells was investigated. Activated T cells were cloned from a newly diagnosed diabetic patient, and many CD4 cytotoxic clones were detected. The clone with the highest cytolytic capacity lysed HLA class II compatible islet cells which had been induced by interferon gamma and tumour necrosis factor to express class II antigens. The specificity of the lysis was demonstrated by use of histoincompatible islets, other histocompatible target cells, and blocking by anti-class-II monoclonal antibodies. The results show that a CD4-positive T cell clone can lyse HLA class II matched islet cells; this process may be important in the pathogenesis of type 1 diabetes. PMID- 2902267 TI - Association between villous atrophy in rheumatoid arthritis and a rheumatoid factor and gliadin-specific IgG. AB - 93 patients with rheumatoid arthritis (RA) were examined for histological or other evidence of gut abnormalities. 44 had raised levels of IgG to gliadin, and of these 38 (86%) were also positive for IgA rheumatoid factor (RF). 24 patients (15 with raised levels of IgA RF and wheat protein IgG [AB+] and 9 with normal levels of both antibodies [AB-]) underwent jejunal biopsy. 6 of the AB+ and 1 of the AB- patients had villous atrophy. The AB+ group had lower villous surface/volume ratio and small intestinal lactase concentrations than did the AB- group or age-matched controls. There was no significant difference between the two groups of RA patients in disease severity or treatment regimen. The findings suggest that the gut may play a more important part in the immunopathogenesis of some cases of RA than in others, and that the former may be identified by raised levels of IgA RF and wheat protein IgG. PMID- 2902269 TI - Acute aortic dissection. PMID- 2902270 TI - Flumazenil. PMID- 2902271 TI - Twenty-five years of coronary care. PMID- 2902272 TI - Intercellular adhesion molecules and recurrent infection. PMID- 2902273 TI - Health promotion at work. PMID- 2902274 TI - Role of caesarean section in prevention of mother-infant transmission of hepatitis B virus. AB - 447 infants, born to mothers positive for hepatitis B e antigen and hepatitis B surface antigen (HBsAg), received hepatitis B immunisation. A higher rate of hepatitis B virus (HBV) infection was found at birth in infants delivered vaginally (96/385, 24.9%) than in infants delivered by caesarean section (6/62, less than 10%). At birth, serum HBV-DNA was detected in 13 of 67 infants delivered vaginally, but in none of 30 infants delivered by caesarean section. Caesarean section combined with hepatitis B immunisation is advisable in infants of mothers who are chronic HBsAg carriers with high serum HBV-DNA levels. PMID- 2902275 TI - Medical education and nuclear war. PMID- 2902276 TI - Prevalence of specific reading disability in Egypt. AB - 2878 children from the 2nd and 3rd grades in elementary schools were assessed for their reading ability by means of standardised tests for linguistic ability and rate of letters identification. 84 children (3%) with IQ 90 or more and no evidence of sensory or motor impairment were backward in their reading ability. They were left to proceed in their conventional educational programme for the next 3 years, then reassessed. 47 (2%) children had attained satisfactory reading skills. The 37 (27 boys, 10 girls) who did not improve were diagnosed as having the syndrome of specific reading disability (SRD). The prevalence of SRD among the population surveyed was 1%, and the male to female ratio was 2.7 to 1. The prevalence was far lower than that reported in western countries. How the Arabic language is written and read probably contributes to the low prevalence of SRD among Arabic speaking populations. PMID- 2902277 TI - Coronary heart disease is not preventable by population interventions. PMID- 2902278 TI - AIDS and the workplace. PMID- 2902279 TI - Ciprofloxacin resistance in epidemic methicillin-resistant Staphylococcus aureus. PMID- 2902280 TI - Severe premenstrual asthma. PMID- 2902281 TI - Microbiological safety cabinets and laboratory acquired infection. PMID- 2902282 TI - Islet cell antibody standard serum. PMID- 2902283 TI - Changing prevalence of juvenile-onset diabetes mellitus. PMID- 2902284 TI - Routine antenatal vaginal examinations. PMID- 2902285 TI - Outbreak of amoebiasis in tourists returning from Thailand. PMID- 2902286 TI - Reduction of cytotoxic antibodies after continuous ambulatory peritoneal dialysis in highly sensitised patients. PMID- 2902287 TI - Simplified confirmatory HIV testing. PMID- 2902288 TI - Renal transplantation for dialysis arthropathy. PMID- 2902290 TI - Preventive medicine. PMID- 2902289 TI - Risks of simultaneous therapy with oral aluminium and citrate compounds. PMID- 2902291 TI - Revising RAWP. PMID- 2902292 TI - Danger of MAOI therapy after fluoxetine withdrawal. PMID- 2902293 TI - Carboplatin or cisplatin? PMID- 2902294 TI - Granulocytopenia due to fusidic acid. PMID- 2902295 TI - Prochlorperazine in the elderly. PMID- 2902296 TI - First-trimester biochemical screening for Down syndrome. PMID- 2902297 TI - Food and H2 blockade. PMID- 2902298 TI - Improved whole-body protein turnover after heart-lung transplantation. PMID- 2902299 TI - Inborn errors of metabolism and unexpected infant deaths. PMID- 2902300 TI - Measurement of cardiac output. PMID- 2902301 TI - Protective light shields for neonatal phototherapy. PMID- 2902302 TI - Pseudomonas aeruginosa toxin-A-neutralising antibodies in normal human serum. PMID- 2902303 TI - Typhoid-fever-like syndrome after Ty21a live oral vaccine. PMID- 2902304 TI - Synovial fluid T cells and 65 kD heat-shock protein. PMID- 2902305 TI - Nifedipine and nocturia. PMID- 2902306 TI - Ovalocytosis and malaria. PMID- 2902308 TI - Who's for the thoracic duct? PMID- 2902307 TI - Perception of drug hazards. PMID- 2902309 TI - Barristers debate medicolegal issues. PMID- 2902310 TI - Measles/mumps/rubella vaccine. PMID- 2902311 TI - Salmonella infection and food hygiene. PMID- 2902312 TI - The long-lived men of Greece. PMID- 2902313 TI - Worried sick. PMID- 2902314 TI - HIV infection in drug misusers. PMID- 2902315 TI - In-vivo demonstration of reduced benzodiazepine receptor binding in human epileptic foci. AB - Ten patients with partial epilepsy and five healthy controls had positron emission tomography (PET) of the brain after intravenous administration of the 11C-labelled benzodiazepine (BZ) receptor ligand 'Ro-15 1788'. In all ten patients BZ receptor binding was significantly lower in the epileptic focus than in the contralateral homotopic reference region and the remaining neocortex. No asymmetries in BZ receptor binding were observed between homotopic reference regions in the controls or the non-epileptic regions of patients. These results demonstrate the potential of the BZ receptor as a biochemical marker for display of epileptic foci by PET, and also strengthen the hypothesis that inhibitory mechanisms are disturbed in the epileptic focus. PMID- 2902316 TI - One-year trial of a remote-controlled implantable insulin infusion system in type I diabetic patients. Point Study Group. AB - Twenty remote-controlled insulin pumps (Siemens AG) were implanted into insulin dependent type I diabetic patients for a one-year feasibility trial in four centres. The total observation time was 18.2 patient-years. Three pumps had to be prematurely removed after 101, 141, and 236 days. Patients self-monitored blood glucose levels with a mean of 5.5 (range 1-17) measurements per day. 62.9% of these measurements were in the range 3.33-8.88 mmol/l. 3.25 glucose measurements per patient-month were in the hypoglycaemic range (lower than 2.78 mmol/l) and 2.6 episodes of hypoglycaemia with symptoms were reported per patient-month, of which 0.22 per patient-year required medical attention. The median HbA1c level was 7.6% at baseline (10-90% centile = 5.9-9.1%) and 7.0% at the end of the trial (10-90% centile = 5.7-8.3%) (p less than 0.05). Despite some technical and clinical problems, the pump, when used with a stable insulin preparation, was an effective means of treating insulin-dependent patients. PMID- 2902317 TI - Prednisolone and chlorambucil treatment in idiopathic membranous nephropathy with deteriorating renal function. AB - Eight patients with idiopathic membranous nephropathy whose renal function was deteriorating were given a 6-month course of alternating monthly cycles of prednisolone and chlorambucil. Proteinuria was reduced in all eight, from a mean (SD) of 15.3 (5.9) g/24 h at the start of treatment to 2.1 (1.5) g/24 h at follow up (p less than 0.05). Creatinine clearance increased in six, and the rate of decline was reduced in the other two (group mean 51.6 [17.8] ml/min at the start of treatment and 81.4 [36.8] ml/min at follow-up; p less than 0.05). Adverse effects of chlorambucil were severe, and the daily dose had to be reduced. Prednisolone and chlorambucil treatment can change the natural course of membranous nephropathy even when renal function has started to deteriorate, so treatment can be reserved for high-risk patients. PMID- 2902318 TI - Role of pulmonary alveolar macrophage activation in acute lung injury after burns and smoke inhalation. AB - Bronchoalveolar lavage cells from 42 fire victims and from 18 patients who were smokers attending for diagnostic bronchoscopy (controls) were assessed morphologically and by chemiluminescence. 10 of the victims had inhaled smoke only; 15 had cutaneous burns only; and 17 had combined injury. The combined injury group had significant increases in polymorphonuclear leucocytes and macrophages, especially mature forms, compared with controls. These increases were higher than those expected from the individual injuries. The combined injury group had significantly greater spontaneous chemiluminescence than controls, again greater than that expected by the individual injuries. The chemiluminescence response to stimulation by opsonised bacteria was significantly higher in the combined injury group than in controls, but significantly lower than that in the smoke inhalation only group. The size of the alveolar cellular response to smoke and cutaneous burns suggests that lung damage follows from excess release of inflammatory mediators, exhaustion of the reserve of mature phagocytes and consequent reduced ability to fight bacteria, or both. PMID- 2902320 TI - Pump control of continuous arteriovenous haemodialysis. PMID- 2902319 TI - Lack of benefit of clonidine treatment for short stature in a double-blind, placebo-controlled trial. AB - Twelve short (more than two standard deviations below the mean height for age), prepubertal children (ten boys, two girls) who had a normal peak growth hormone (GH) response to provocative stimulation with clonidine (more than 10 ng/ml) were enrolled in a double-blind, placebo-controlled, crossover study of the effects of a single, nightly dose of clonidine (0.1 mg/m2 by mouth). The children's mean age was 7.2 years (range 3.6-10.5 years). The results of 6 months of clonidine therapy were compared with those of 6 months of placebo. Clonidine therapy resulted in no significant difference in height standard deviation score, growth velocity, bone age, 24 h integrated GH concentration, peak GH response to clonidine stimulation, levels of insulin-like growth factor 1, or predicted height by the RWT method. In contrast to other studies, this study shows no sustained increases in GH production or in improved growth velocity with long term administration of a single daily dose of clonidine. Furthermore, this study demonstrates the need for well-designed, placebo-controlled trials in paediatrics. PMID- 2902321 TI - Agoraphobia. PMID- 2902322 TI - Hepatic haemangioma--a suitable case for treatment? PMID- 2902323 TI - Surgical insurrection. PMID- 2902324 TI - ACE inhibitors--the trickle becomes a flood. PMID- 2902325 TI - People need people. PMID- 2902326 TI - Prevention of transmission of human immunodeficiency virus in Africa: effectiveness of condom promotion and health education among prostitutes. AB - Condom use was assessed after a programme of education about the acquired immunodeficiency syndrome and a condom distribution programme in a well characterised prostitute population in Nairobi. Women received their education at group meetings (barazas) and at individual counselling sessions during which they were given the results of serological tests for the human immunodeficiency virus (group 1) or at barazas only (group 2), or through very little of either (group 3). During the counselling sessions free condoms were distributed. Before either of the programmes started, 10%, 9%, and 7% of groups 1, 2, and 3 women, respectively, reported occasional use of condoms. By November 1986, 80%, 70%, and 58% of groups 1, 2, and 3 women, respectively, reported at least some condom use. The mean frequency of condom use was 38.7 (SD 31.8)%, 34.6 (34.5)%, and 25.6 (29.5)% of sexual encounters in groups 1, 2, and 3 women. 20 of 28 women who were non-condom-users seroconverted compared with 23 of 50 women who reported some use of condoms. PMID- 2902327 TI - Blood pressure in British children: associations with adult blood pressure and cardiovascular mortality. AB - Blood pressure was measured in 4186 children aged 5 to 7 years in 9 British towns. 3 towns had high, 3 had intermediate, and 3 had low adult blood pressure levels observed in an earlier study of middle-aged men. Significant differences between the towns were found for the children's mean systolic blood pressure (range 96.7 to 102.4 mm Hg) and diastolic pressure (range 55.9 to 60.3 mm Hg). The pattern of systolic blood pressure differences in children was similar to that observed in the study of middle-aged men (r = 0.65). The town mean systolic pressures in children show an association with standardised mortality ratios for cardiovascular disease in adults. The pattern of geographical differences in blood pressure observed in British adult men may have its origins early in life. PMID- 2902329 TI - Hookworm control. PMID- 2902328 TI - Development of anti-idiotypic antibodies against tumour antigens and autoantigens in ovarian cancer patients treated intraperitoneally with mouse monoclonal antibodies. AB - Repeated intraperitoneal administration of therapeutic amounts of radiolabelled (iodine-131) murine monoclonal antibodies leads to the development of an immune response in the recipient, part of which is directed against the variable region (idiotype) of the administered antibody (anti-Id1 response). Human immunoglobulin purified from these patients inhibits binding of the original murine monoclonal antibody to its target tumour antigen and therefore represents an "internal image" of the tumour antigen. Furthermore, this study recorded the development of human antibodies that themselves bind to the tumour antigen, with a specificity identical or similar to that of the injected monoclonal antibody. These human antitumour antibodies are probably generated by way of the idiotypic network and confirm the existence of the idiotypic network. Accompanying this antitumour response the transient development of autoantibodies that react with connective tissue components of liver, kidney, spleen, and diaphragm was also observed. PMID- 2902330 TI - Anal size in constipated and non-constipated children. PMID- 2902331 TI - Intracranial aneurysm rupture as an occupational accident. PMID- 2902332 TI - Sleeping position and cot death. PMID- 2902333 TI - Ciprofloxacin and tenosynovitis. PMID- 2902334 TI - Renal transplantation for dialysis arthropathy. PMID- 2902335 TI - Post-mortem allogeneic vein for graft as vascular access in chronic haemodialysis. PMID- 2902336 TI - Cyclosporin encephalopathy associated with fat embolism induced by the drug's solvent. PMID- 2902337 TI - Disordered smell. PMID- 2902338 TI - Papillomavirus DNA in cervical carcinoma specimens from central China. PMID- 2902339 TI - Which blood pressure? PMID- 2902340 TI - Endoscope exchange in biliary prosthesis procedures. PMID- 2902342 TI - Has the incidence of Pneumocystis carinii pneumonia in cancer patients increased with the AIDS epidemic? PMID- 2902341 TI - Is coeliac disease a premalignant state? PMID- 2902343 TI - HIV infection after plasma donation in Valencia: yet another case. PMID- 2902344 TI - Reversible bronchoconstriction with nebulised pentamidine. PMID- 2902345 TI - Protective effect of oestrogen in pancreatic cancer. PMID- 2902346 TI - Inhibitors of cyclo-oxygenase and lipoxygenase in onions. PMID- 2902347 TI - Piracetam for choreoathetosis. PMID- 2902348 TI - Microalbuminuria and vascular permeability. PMID- 2902349 TI - Fluctuating serum cholesterol. PMID- 2902350 TI - Lytic IgG anti-endothelial cell antibodies in vasculitis. PMID- 2902351 TI - Leaving the anaesthetised patient. PMID- 2902352 TI - The elderly smoker. PMID- 2902353 TI - The Edinburgh Declaration. PMID- 2902354 TI - Polls on attitudes to abortion. PMID- 2902355 TI - Gastroenteritis in food handlers. PMID- 2902356 TI - Pictures for the developing world. PMID- 2902357 TI - Rubella vaccination: persistence of antibodies for 10-21 years. PMID- 2902358 TI - Prenatal treatment of fetal alloimmune thrombocytopenia. PMID- 2902359 TI - Dysentery due to multiresistant Shiga bacillus in rural Iran. PMID- 2902361 TI - Nalidixic-acid resistant Shigella dysenteriae type 1 in eastern India. PMID- 2902362 TI - Hallucinations during morphine but not during oxycodone treatment. PMID- 2902360 TI - Ketoconazole for subcutaneous phycomycosis. PMID- 2902363 TI - Resistant malaria and the Sudan floods. PMID- 2902364 TI - Sunlight as disinfectant. PMID- 2902365 TI - Ultraviolet light for sterilisation. PMID- 2902366 TI - High prevalence of antibody to human herpesvirus-6 and seroconversion associated with rash in two infants. PMID- 2902367 TI - Acute radiation skin reaction and persistent photosensitivity after benoxaprofen. PMID- 2902368 TI - Reversible limb-girdle muscular dystrophy. PMID- 2902369 TI - Diet and cyclical mastopathy. PMID- 2902370 TI - Glutamate dehydrogenase activity in amyotrophic lateral sclerosis. PMID- 2902371 TI - ISIS-2 and anticoagulation policy after anterior infarcts. PMID- 2902372 TI - Mechanism of late benefit in ISIS-2. PMID- 2902373 TI - Polymorphic O-demethylation of codeine. PMID- 2902374 TI - Naevus of Jamaica. PMID- 2902375 TI - Urokinase versus tissue plasminogen activator in pulmonary embolism. PMID- 2902376 TI - Latent drug injury: failure of Dutch diethylstilboestrol action. PMID- 2902377 TI - IPPF guidance on HIV transmission. PMID- 2902378 TI - National AIDS Trust. PMID- 2902379 TI - Intensive therapy for children with acute lymphoblastic leukaemia and unfavourable presenting features. Early conclusions of study CCG-106 by the Childrens Cancer Study Group. AB - 229 children with acute lymphoblastic leukaemia (ALL) and with clinical and laboratory features associated with a high risk of treatment failure entered a randomised study of three treatment regimens. Before 1981, such patients had a 3 year event-free survival (EFS) of 47%. Two intensive therapies, the Berlin Frankfurt-Munster (BFM) 76/79 regimen and the New York (NY) regimen were compared with a control regimen that had achieved the best outcome in previous Trials. Data on 214 cases (93.4%) were analysed. The 3-year EFS was 78% for the BFM and NY regimens and 49% for the control regimen, a significant difference. The differences persisted after stratification by age at onset, sex, white blood cell count at diagnosis, and marrow blast morphology. Control patients were 2.7 times more likely to fail induction, to die, or to relapse than were patients on the intensive regimens. PMID- 2902380 TI - Protein C deficiency and portal thrombosis in liver transplantation in children. AB - Changes in plasma protein C and antithrombin concentrations after liver transplantation were monitored in fourteen children and a control group of fourteen adults. In the children, there was a persistent deficiency in the plasma concentration of protein C and a less pronounced deficiency in antithrombin during the early postoperative period, causing a hypercoaguable state. A concomitant rise in plasminogen activator inhibitor further increased the risk of thrombosis by inhibiting fibrinolysis. These changes coincided with the peak incidence of portal vessel thrombosis (4-10 days). Replacement of plasma antithrombin, together with heparin, did not prevent portal thrombosis in two of the children. It is concluded that successful prevention will require protein C replacement together with antithrombin supplements up to, but not exceeding, normal plasma activity. PMID- 2902381 TI - Envelope cross-reactivity in Western blot for HIV-1 and HIV-2 may not indicate dual infection. AB - Serological identification of infection with human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) by western blot alone may not be sufficient to diagnose dual infection. Extensive cross-reactions (eg, to envelope glycoprotein antibody) are seen on heterologous western blots. The use of other techniques, in this case competitive enzyme-linked immunosorbent assays, indicates that blot patterns previously thought to demonstrate simultaneous dual infections should be interpreted with caution. PMID- 2902382 TI - Increase in clonogenic tumour cells in bone marrow of patients with multiple myeloma treated with vincristine, doxorubicin, and methylprednisolone. AB - The relation between clonogenic myeloma cells, assayed in vitro, and clinical status was studied in 20 patients with multiple myeloma before and after VAMP therapy (vincristine, doxorubicin, and methylprednisolone). 14 patients showed an improvement in clinical status, as judged by a fall in myeloma protein and a decrease in plasmacytoid myeloma cell infiltration in the bone marrow. However, in 11 of these 14, there was an increase in the number of clonogenic myeloma cells. This suggests that the treatment changed the myeloma cell population in the residual bone marrow. To be effective, subsequent chemotherapy should be aimed at destroying this population of myeloma cells. PMID- 2902383 TI - Participation of dendritic cells in vascular lesions of chronic rejection of human allografts. AB - Immunohistochemical techniques were used to investigate the pathogenesis of obliterative arteriopathy, a major obstacle to long-term solid organ allograft survival. T-lymphocytes, macrophages, and proliferating smooth muscle cells made up most of the thickened intima. More importantly, S100-protein-positive dendritic cells were also present in the intima, especially during active inflammation and smooth muscle cell proliferation. These are phenotypic characteristics of tissue "dendritic" cells, pivotal accessory cells in T dependent immune reactions. Their localisation in the arterial wall signals the presence of an ongoing immunological reaction directed at native constituents of the artery or at exogenous antigens which permeate the damaged vessel wall. PMID- 2902384 TI - Increase in myocardial Gi-proteins in heart failure. AB - The contractile response and myocardial content of Gi-proteins were examined in cardiac preparations from explanted hearts of four different patients with end stage heart failure. Three patients had idiopathic dilated cardiomyopathy and one patient had inflammatory heart disease. Preparations from patients with idiopathic dilated cardiomyopathy showed reduced contractile response to the cAMP increasing agent isoprenaline and an increase in myocardial Gi-proteins, compared with preparations from non-failing hearts. Therefore it is conceivable that an increase in myocardial Gi-proteins is causally related to heart failure due to idiopathic dilated cardiomyopathy. In the preparation from the patient with inflammatory heart disease the contractile response to isoprenaline was not reduced and likewise content of Gi-proteins was not changed. PMID- 2902385 TI - Making the headless chicken squawk. PMID- 2902386 TI - Self-esteem. PMID- 2902388 TI - Endoscopic sphincterotomy--a cautionary note. PMID- 2902387 TI - Suxamethonium myalgia. PMID- 2902389 TI - Whooping cough in infants. PMID- 2902390 TI - Notification of HIV carriers: possible effect on uptake of AIDS testing. AB - Passing of the AIDS Prevention Bill, which demands the notification of human immunodeficiency virus (HIV) carriers, seems imminent in Japan. Its effect on people's willingness to be tested for the HIV antibody was assessed among heterosexual subjects (students, office workers) and groups at high risk of the acquired immunodeficiency syndrome (AIDS) (prostitutes, homosexual males) by means of a questionnaire. More than 70% of the 811 students and 509 workers replied that, if notification became mandatory, they would agree to be tested but 10% of the males and 17% of the females in these two groups would prefer testing at institutes not complying with the clause; all 198 prostitutes said that they would be prepared to undergo testing but 35% of them would prefer to go to non complying clinics; 45% (410) of 902 homosexual males replied that they would refuse testing, and 65% of those who would agree to be tested (492) would prefer to go to non-complying clinics. These findings strongly suggest that when the bill is passed the greater the self-perceived risk of HIV infection the poorer will be the uptake of AIDS testing. Hence the bill would be counterproductive in the surveillance of potential HIV carriers. PMID- 2902391 TI - Non-invasive management of fetal obstructive uropathy. AB - Fetal outcome was studied in 43 consecutive cases of fetal obstructive uropathy in which no prenatal treatment was undertaken: 12 babies survived. In the 31 who did not survive, oligohydramnios was present in 24 and urethral atresia was the most common cause of obstruction (in 27). At necropsy, bilateral renal dysplasia was found in 23 and pulmonary hypoplasia in 13; 16 had structural or chromosomal anomalies, less than half of which were detected by prenatal ultrasound. In the survivors, 8 had posterior urethral valves, 1 had oligohydramnios, and 2 had associated anomalies. Obstructive uropathy is often associated with other anomalies which may escape prenatal ultrasound detection, and studies to determine the efficacy of intrauterine decompression techniques must allow for this observation. PMID- 2902392 TI - The increment in the anion gap: overextension of a concept? AB - The calculation of the anion gap is widely used in the diagnosis of metabolic acidosis. It is often taught that the increment in the anion gap will exactly match the fall in serum bicarbonate during a simple metabolic acidosis of the high anion gap type; if the changes in the anion gap and bicarbonate level are not equivalent, a second acid-base disorder should be suspected. The assumptions upon which this formulation is based are largely unsubstantiated. This review critically examines these assumptions and their clinical implications. Discrepancies between the increment in the anion gap and the reduction in serum bicarbonate must be interpreted cautiously. PMID- 2902393 TI - Screening for breast cancer: examination and reporting of histopathological preparations. PMID- 2902394 TI - Therapeutic suggestions during general anaesthesia. PMID- 2902395 TI - Early thrombosis in kidney grafted into patient treated with erythropoietin. PMID- 2902396 TI - Is cyclosporin toxic to endothelial cells? PMID- 2902397 TI - Cyclosporin toxicity and colitis. PMID- 2902398 TI - Houseplant peritonitis. PMID- 2902399 TI - Classification of primary gut lymphomas. PMID- 2902400 TI - Quality of life on angina therapy. PMID- 2902402 TI - Leukemia in young children. PMID- 2902401 TI - Premorbid neuropathology in schizophrenia. PMID- 2902403 TI - Treatment of essential thrombocythaemia by alpha 2a interferon. PMID- 2902404 TI - Pseudoglycosuria and ciprofloxacin. PMID- 2902405 TI - Potassium and fatigue. PMID- 2902406 TI - Negative association between the human T-cell leukaemia virus type I and large granular lymphocyte leukaemia in Japan. PMID- 2902407 TI - Progression of chronic renal failure. PMID- 2902408 TI - Lipoprotein(a), cholesterol, and coronary heart diseases. PMID- 2902409 TI - Serological crossreaction of human herpesvirus-6 with cytomegalovirus. PMID- 2902410 TI - Pruritus preceding the development of polycythaemia vera. PMID- 2902411 TI - Cocaine and HIV seropositivity. PMID- 2902412 TI - Tenth case of HIV transmission after plasma donation. PMID- 2902413 TI - Homosexual role separation and spread of AIDS. PMID- 2902414 TI - Sulphasalazine does not select for Escherichia coli with adhesive properties in ulcerative colitis. PMID- 2902415 TI - Influenza-like syndrome after terconazole. PMID- 2902416 TI - Acute hepatitis B infection after treatment with heat-inactivated factor VIII concentrate. PMID- 2902417 TI - Improvement in hypertrophic hepatic osteoarthropathy after liver transplantation. PMID- 2902418 TI - Is Campylobacter pylori a zoonosis? PMID- 2902419 TI - Enterovirus infection in peripartum cardiomyopathy. PMID- 2902420 TI - Clinical spectrum of neuroleptic malignant syndrome. PMID- 2902421 TI - Microalbuminuria and posture. PMID- 2902422 TI - Cytomegalovirus matching in renal transplantation. PMID- 2902423 TI - Thyroid papillary carcinoma in HLA identical sibs. PMID- 2902424 TI - New mutations in Duchenne muscular dystrophy. PMID- 2902425 TI - Gastric angiodysplasia associated with primary biliary cirrhosis. PMID- 2902426 TI - Selection of blood donors in malaria-endemic countries. PMID- 2902428 TI - AIDS in the UK and worldwide. PMID- 2902427 TI - Radiotherapy overdose. PMID- 2902429 TI - Occupational exposure to ribavirin aerosols. PMID- 2902430 TI - Pregnancy, transfusions, and HIV. PMID- 2902432 TI - AIDS in Scotland. PMID- 2902431 TI - World AIDS Day. PMID- 2902433 TI - Prohibition of HIV testing without medical supervision. PMID- 2902435 TI - Cushing's disease of the kidney. PMID- 2902434 TI - Urinary tract candidosis. PMID- 2902436 TI - Classification of mental disorder in primary care. PMID- 2902437 TI - Neuromuscular blockers in patients with burns. PMID- 2902438 TI - Wellcome steps into the breach once more. PMID- 2902439 TI - Genetics of classic Alport's syndrome. AB - 41 families with classic Alport's syndrome (hereditary nephritis with sensorineural deafness) were studied. All their pedigrees were compatible with X linked inheritance. DNA probes were used to investigate genetic linkage in these families. Linkage to probe S21 (DXS17) was confirmed (LOD score = 4.72 at 0 = 0.06), localising the gene for Alport's syndrome to the middle of Xq; thus the disorder is X-chromosomal in nature. PMID- 2902440 TI - Aluminum, chemical physiology, and Alzheimer's disease. PMID- 2902441 TI - Perichondritis. AB - 5 children with abdominal pain of costochondral origin were seen between October, 1987, and February, 1988. 4 were initially misdiagnosed and had unnecessary and costly investigations and inappropriate treatment. An accurate history and a thorough examination are essential to reach the correct diagnosis. A short course of mefenamic acid was effective in all but one child, who responded to a local injection of methylprednisolone. PMID- 2902442 TI - Nottingham study of neurotic disorder. PMID- 2902443 TI - Breastfeeding beyond twelve months. PMID- 2902444 TI - von Willebrand factor abnormalities in two patients with uraemia. PMID- 2902445 TI - Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus. PMID- 2902446 TI - Thrombocytosis after cyclosporin therapy in child with nephrotic syndrome. PMID- 2902447 TI - Indigenised pharmaceuticals and aplastic anaemia. PMID- 2902448 TI - Mefenamic acid overdose mimicking brainstem stroke. PMID- 2902449 TI - Tamoxifen and endometrial cancer. PMID- 2902450 TI - Patient's choice of animal or human insulin. PMID- 2902452 TI - Cerebral vasospasm and unruptured aneurysm in thunderclap headache. PMID- 2902451 TI - Carbon dioxide and acute mountain sickness. PMID- 2902453 TI - Making insect repellents safe. PMID- 2902454 TI - Tumour cell morphometry and response to chemotherapy in ovarian cancer. PMID- 2902455 TI - Alterations in T cell subsets in multiple sclerosis and other autoimmune diseases. PMID- 2902456 TI - Leukaemia "outbreaks". PMID- 2902457 TI - Listeria and food. PMID- 2902458 TI - Non-availability of ether. PMID- 2902459 TI - ABO incompatibility. PMID- 2902460 TI - HIV and orogenital transmission. PMID- 2902461 TI - Ditiocarb in HIV infection. PMID- 2902462 TI - Herpetic bronchitis and case definition of AIDS. PMID- 2902463 TI - Seropositivity to HIV in Hodgkin's disease. PMID- 2902464 TI - Relation between motoneuron disease and past poliomyelitis. PMID- 2902465 TI - Electrical stimulation for disuse muscle atrophy. PMID- 2902466 TI - Thromboembolism and air travel. PMID- 2902468 TI - Mental handicap and the community. PMID- 2902469 TI - Acute aortic dissection. PMID- 2902470 TI - Attitudes to alcohol. PMID- 2902467 TI - Hospital administrator's paradox. PMID- 2902471 TI - Cerebral blood flow in panic disorder. PMID- 2902472 TI - Strange allergy to chicory. PMID- 2902473 TI - The elderly smoker. PMID- 2902474 TI - Effect of cigarette smoking on Langerhans' cells. PMID- 2902475 TI - Screening for aortic aneurysm. PMID- 2902476 TI - Tissue plasminogen activator versus urokinase. PMID- 2902477 TI - European attitudes to heart disease prevention. PMID- 2902478 TI - Human intestinal lactase and Lamarckian evolution. PMID- 2902479 TI - Routine ultrasound scanning in twin pregnancies. PMID- 2902480 TI - Death takes a holiday. PMID- 2902481 TI - Proliferation of non-psoriatic human fibroblasts in vitro by serum from patients with psoriasis. PMID- 2902482 TI - Screening for infections in pregnancy. PMID- 2902483 TI - Brain damage and spontaneous correction of hyponatraemia. PMID- 2902484 TI - Breastfeeding babies of HBsAg-positive mothers. PMID- 2902485 TI - Salt, pregnancy, hypertension--and literature searches. PMID- 2902486 TI - Randomised trials and informed consent. PMID- 2902487 TI - AIDS control in India. PMID- 2902489 TI - AIDS education. PMID- 2902488 TI - Mass voluntary HIV testing. PMID- 2902490 TI - Instituting a smoking policy. PMID- 2902491 TI - Controlled trial of urgent endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy versus conservative treatment for acute pancreatitis due to gallstones. AB - 121 patients with acute pancreatitis thought to be due to gallstones were randomised to treatment with urgent endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES) or with conventional treatment. They were stratified by predicted severity of the attack, according to the modified Glasgow system. ERCP was done within 72 h, and if common bileduct stones were identified, patients underwent ES immediately to extract the stones. There were fewer complications in the 59 patients who underwent ERCP +/- ES than among the 62 treated conventionally, the difference being confined to those whose attacks were predicted to be severe (6/25 ERCP +/- ES [1 death] compared with 17/28 conventional treatment [5 deaths]). Hospital stay was also shorter for patients with severe attacks who underwent ERCP +/- ES than for those who received conservative treatment (median 9.5 versus 17.0 days). PMID- 2902492 TI - Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. AB - Paired sera from 40 male patients with acute myocardial infarction (AMI), 30 male patients with chronic coronary heart disease (CCHD), and 41 controls, matched for sex, age, time, and locality were investigated for antibodies to a novel type of Chlamydia sp, TWAR, and to chlamydial lipopolysaccharide (LPS) group antigen. 27 patients with AMI (68%), and 15 (50%) patients with CCHD had raised IgG (greater than or equal to 128) and/or IgA (greater than or equal to 32) titres in the microimmunofluorescence test with chlamydia TWAR. Both frequencies were significantly higher than in the controls (7, 17%). 26 (68%) of 38 patients with AMI also showed a significant seroconversion in enzyme immunoassay with LPS antigen; this response was absent in all patients with CCHD and all but 1 of the controls. Chronic chlamydial infection could be a factor in the pathogenesis of cardiovascular diseases. PMID- 2902493 TI - Localisation of 11 beta-hydroxysteroid dehydrogenase--tissue specific protector of the mineralocorticoid receptor. AB - In vitro the mineralocorticoid receptor is non-specific and does not distinguish between aldosterone and cortisol. In vivo certain tissues with this receptor are aldosterone selective (eg, kidney and parotid) whereas others with the same receptor are not (eg, hippocampus and heart). Experiments in rats showed that 11 beta-hydroxysteroid dehydrogenase (which converts cortisol to cortisone in man and corticosterone to 11-dehydrocorticosterone in the rat) was much more highly concentrated in aldosterone-selective tissues than in non-selective tissues. The localisation in the selective tissues was such that the enzyme could act as a paracrine or possibly an autocrine mechanism protecting the receptor from exposure to corticosterone. Autoradiographic studies showed that protection is lost when the enzyme is inhibited; 3H-corticosterone and 3H-aldosterone were bound to similar sites. These findings seem to explain why sodium retention, hypokalaemia, and hypertension develop in subjects with congenital deficiency of 11 beta-OHSD and those in whom the enzyme has been inhibited by liquorice. PMID- 2902494 TI - Effect of cimetidine on survival after gastric cancer. AB - The effect of cimetidine on survival was investigated in 181 patients with gastric cancer. Immediately after operation or the decision not to operate, the patients were randomised in double-blind fashion to placebo or cimetidine 400 mg twice daily for two years or until death, with review every three months. Median survival in the cimetidine group was 450 days (range 1-1826) and in the placebo group 316 days (1-1653). The relative survival rates (cimetidine/placebo) were 45%/28% at 1 year, 22%/13% at 2 years, 13%/7% at 3 years, 9%/3% at 4 years, and 2%/0% at 5 years. Survival in the cimetidine group was significantly longer than in the placebo group. PMID- 2902495 TI - Determinants of blood pressure in snorers. AB - To examine the hypothesis that the tendency to raised blood pressure in snorers is associated with nocturnal hypoxaemia and snoring, blood pressure was measured and snoring, oxyhaemoglobin saturation (SaO2), and thoraco-abdominal movements were monitored overnight in 372 snorers. Snoring was quantified as number of snores per hour of sleep (snoring index). The data were analysed by multiple linear regression of diastolic blood pressure against age, body mass index (BMI), apnoea-hypopnoea index (AHI, number of episodes per hour), snoring index, and SaO2. Diastolic blood pressure correlated significantly with BMI, AHI, and mean nocturnal oxygen saturation, but not with the snoring index. However, snoring index correlated with BMI, AHI, and mean nocturnal oxygen saturation. Snoring is thus not a direct risk factor for hypertension, but may influence blood pressure via its association with obesity, obstructive sleep apnoea, and nocturnal hypoxaemia. PMID- 2902496 TI - Antihypertensive treatment, myocardial infarction, and nocturnal myocardial ischaemia. AB - Patients with critical coronary stenoses or hypertrophied ventricles have impaired coronary vasodilator reserve and are at greatest risk of myocardial ischaemia or infarction if subendocardial perfusion pressure falls below the lower threshold of bloodflow autoregulation. During sleep, antihypertensive treatment may cause coronary artery perfusion pressure to fall below these limits in such patients. Unrecognised nocturnal hypotension may be one reason why treatment has not diminished the risk of myocardial infarction in patients with hypertension. PMID- 2902497 TI - Management of acute variceal bleeding. PMID- 2902498 TI - Laser lithotripsy: a review of 20 years of research and clinical applications. AB - Four new technologies have transformed the treatment of urinary calculi: electrohydraulic lithotripsy, ultrasonic lithotripsy, extracorporeal shock wave lithotripsy, and laser lithotripsy. Initial attempts to ablate urinary calculi by continuous wave CO2, ruby, and Nd-YAG lasers failed because of excess thermal injury and inability to pass the laser energy via a flexible fiber. Basic laboratory studies then demonstrated that short pulsed laser energy absorbed by the calculus resulted in fragmentation. The parameters that produced optimal urinary calculus fragmentation were found using the flashlamp pumped tunable dye laser, with the following parameters: wavelength: 504 nm; pulse duration: 1 microsec; fiber: 250 micro silica-coated quartz; repetition: 5-20 Hz. Use of pulsed dye laser caused no tissue damage. The mechanism of fragmentation is light absorption, plasma development, and repetitive acoustic shock wave action with resultant fragmentation. The techniques for application of laser to calculi have been successful, and new, miniature instruments have been developed. Laser lithotripsy is a successful method for fragmenting ureteral calculi. The small caliber of the laser fiber makes this method useful for treating calculi in narrow, tortuous ureters; impacted calculi; distal calculi in ureters that cannot be dilated, via the percutaneous route for stones in calyces or impacted in the upper ureter. Investigations are continuing to optimize fragmentation of harder calculi and to use laser fragmentation within the kidney. Laser lithotripsy may also be used to fragment biliary calculi. PMID- 2902499 TI - Laser lithotripsy: animal studies of safety and efficacy. AB - The safety and efficacy of pulsed tunable dye laser fragmentation of common bile duct stones was assessed in pigs. Laser pulses were conducted through a flexible quartz fiber that was in direct contact with stones that had been surgically implanted into the common bile duct. All calculi were rapidly fragmented into small pieces without significant damage to the common bile duct. The immediate and delayed effects of pulsed lasers on the common bile duct were also evaluated. The common bile duct demonstrated a high tolerance to laser-induced damage even when the laser was discharged directly into the bile duct wall. These results suggest that laser lithotripsy can be performed in humans with a high degree of safety and efficacy. PMID- 2902500 TI - The pulsed dye laser versus the Q-switched Nd:YAG laser in laser-induced shock wave lithotripsy. AB - To date, there are two fairly well-established alternatives for laser-induced shock-wave lithotripsy in clinical practice. The Q-switched Nd:YAG laser is distinguished by the high-stone selectivity of its coupler systems. The necessity of a coupler system and its fairly small conversion rate of light energy into mechanical energy present serious drawbacks. Furthermore, the minimal outer diameter of the transmission system is 1.8 mm. The pulsed-dye laser can be used with a highly flexible and uncomplicated 200-micron fiber. However, the laser system itself is more complicated than the Q-switched Nd:YAG laser and requires a great deal of maintenance. Biological evaluation of damage caused by direct irradiation shows that both laser systems produce minor damage of different degrees. YAG laser lithotripsy with the optomechanical coupler was assessed in 31 patients with ureteral calculi. The instability and limited effectiveness of the fiber application system necessitated auxiliary lithotripsy methods in 14 cases. Dye-laser lithotripsy is currently being tested in clinical application. Further development, such as systems for blind application or electronic feedback mechanisms to limit adverse tissue effects, have yet to be optimized. Nevertheless, laser-induced shock-wave lithotripsy has the potential to become a standard procedure in the endourologic management of stone disease. PMID- 2902501 TI - Changes in teeth and gingiva of dogs following laser surgery: a block surface light microscope study. AB - The effect of laser surgery on tissues of the periodontal apparatus was studied histologically in dogs using block surface light microscopy, a novel microscopical method. With this approach, changes in the hard and soft tissue components were concomitantly demonstrated; the method enabled preservation of the in situ relationship between these components. Following laser surgery, healing in the gingiva was delayed as suggested by the presence of epithelial ulcerations and dense inflammatory infiltrate. In the enamel and cementum the application of laser resulted in crater-like defects that could be avoided only partially by insertion of a tinfoil shield into the gingival sulcus. In the vicinity of the cementoenamel junction these defects were filled with epithelium or periodontal ligament fibers; the close proximity of the hard and soft tissues at the defect sites suggested occurrence of new attachment. Enamel defects located coronal to the gingiva contained bacterial plaque. These histologic results do not demonstrate any substantial advantage of laser over conventional knife gingivectomy. Such advantage may be accomplished with the design of a special intraoral handpiece and further experiments. PMID- 2902502 TI - Involvement of corticotropin-releasing factor in restraint stress-induced anorexia and reversion of the anorexia by somatostatin in the rat. AB - The mechanism by which restraint stress induces suppression of food intake and the influence of intracerebroventricular (icv) administration of somatostatin on the anorexia induced by restraint stress were examined in the rat. Ninety minutes of restraint stress reduced food intake of rats to approximately 60% that of control. Anorexia induced by 90 min restraint stress was partially reversed by icv administration of alpha-helical CRF (9-41), a corticotropin-releasing factor (CRF) antagonist, and completely reversed by anti-CRF gamma-globulin. These results provide further evidence in support of the theory that CRF is involved in the inhibitory mechanism of food intake in restraint stress. ICV administration of somatostatin 14 and SMS 201-995, an analog of somatostatin, also reversed restraint stress-induced anorexia. It is, therefore, suggested that somatostatin may counteract the suppressive action of CRF on food intake in stress. PMID- 2902503 TI - The effect of neuroleptics on dysfunction in a prefrontal substrate of sustained attention in schizophrenia. AB - Regional brain metabolism was measured in patients with schizophrenia during the performance of auditory discrimination to evaluate the effect of neuroleptic medication on the middle prefrontal cortex, an area that appears to be an important biological determinant of the sustained attention required of subjects in this task. While unmedicated patients with schizophrenia have lower than "normal" metabolic rates in this cortical area that are unrelated to performance, patients receiving neuroleptics appear to have this metabolic deficit attenuated with higher metabolism in this area associated with greater accuracy of performance. This change occurs in the context of differential neuroleptic effects on the cortical regions of the frontal cortex, increased metabolism in the basal ganglia, thalamus and temporal lobes, and no apparent effect in the parietal and occipital cortices. The findings suggest that only part of the abnormality in the prefrontal cortex determination of sustained attention in schizophrenia is sensitive to neuroleptic treatment. PMID- 2902504 TI - Determinants of translational initiation efficiency in the atp operon of Escherichia coli. AB - Transcription and translation of the atp genes encoding the subunits b, delta, alpha, gamma and epsilon of the Escherichia coli H+-ATPase were studied. The nature and quantities of the respective transcripts initiated from different promoters were compared with overall expression rates thus yielding accurate information about relative translational efficiency and its coupling to mRNA levels. Part of the highly efficient subunit c gene translational initiation region (TIR) was used as a tool in manipulating the TIRs of the other genes. Rate control of atp cistron translation occurs at the initiation level and is determined locally by each gene's TIR. In this way, individual subunit synthesis rates are set to match the requirements for H+-ATPase assembly. There is no (or very restricted) translational coupling between the cistrons. Translational initiation rates of the normally weakly expressed atp genes could be increased by up to a factor of 27 by manipulating the sequences upstream of the start codons, despite biased codon usages. In the presence of an improved upstream sequence, the N-terminal sequence of the subunit gamma gene exerted a limiting effect. This could be relieved by altering the sequence of the first seven codons. The levels of subunit gamma mRNA were more sensitive to changes in translational efficiency than the concentrations of the other atp mRNAs. The relationships between initiation efficiency and primary and secondary structure in the natural and manipulated atp TIRs are discussed in detail. PMID- 2902505 TI - The expression of mutant pilins in Pseudomonas aeruginosa: fifth position glutamate affects pilin methylation. AB - The expression within Pseudomonas aeruginosa PAO1 of three mutant pilin genes from P. aeruginosa PAK was studied to determine their effects on pilin stability, translocation into the membrane, leader peptide removal, and methylation of the mature N-terminal phenylalanine. The results revealed that a deletion of 4 or 8 amino acids within the immediate N-terminus of pilin had deleterious effects upon leader peptide cleavage. In addition, while the 4-amino-acid deletion did not affect pilin partitioning into the membrane, the 8-amino-acid deletion decreased the amount of pilin found within the membrane fraction. Of considerable interest was the finding that the mutation within the mature pilin of the glutamate at position 5 to a lysine did not prevent leader peptide removal but did inhibit the methylation of the N-terminal phenylalanine. PMID- 2902506 TI - Cloning of a novel pilin-like gene from Bordetella pertussis: homology to the fim2 gene. AB - A search for pilin genes in a Bordetella pertussis (Bp) genomic library has led to the identification of several clones which hybridize to synthetic oligonucleotides with sequences derived from amino acid sequences of Bp fimbrial subunits. One of these clones (corresponding to a gene we have named fimX) contains an open reading frame encoding a protein with a molecular weight of about 20 kD and a sequence similar but not identical to the fimbrial subunit fim2 and to other fimbrial protein sequences. In this communication we present the cloning and nucleotide sequence of the fimX gene and its homology to the fim2 gene. A genomic analysis on the positional relationship between the two genes is also presented. PMID- 2902507 TI - Cell-surface properties of enterotoxigenic and cytotoxic Salmonella enteritidis and Salmonella typhimurium: studies on hemagglutination, cell-surface hydrophobicity, attachment to human intestinal cells and fibronectin-binding. AB - Thirteen Salmonella enteritidis and S. typhimurium strains with smooth or rough colony morphology were investigated for their surface properties based on hemagglutination (HA), hydrophobicity, and fibronectin-binding profiles. The strains showed 5 different patterns of HA which was mannose-sensitive. The rough strains possessed comparatively greater number of fimbriae than the corresponding smooth strains and also attached to human intestinal cells in greater numbers. The Salmonella strains used in this study interacted with fibronectin and its 29 kDa N-terminal fragment to varied extents. These properties may be helpful in broadening the prospective interaction capabilities of Salmonella organisms with the host surfaces. PMID- 2902508 TI - The use of respiratory stimulants in organophosphates' intoxication. AB - 1. Depression of the respiratory center causing acute respiratory insufficiency is the main cause of death in acute poisoning with organophosphates (OP) 2. Various authors recommend the use of respiratory stimulants as an adjuvant to the usual therapeutic arsenal. 3. This survey of the literature was undertaken in order to explore the theoretical basis for this therapeutic attitude and to critically assess its usefulness. 4. The conclusion of this review is that respiratory stimulants should not be used in the treatment of acute organophosphates' intoxication in human beings. PMID- 2902509 TI - The detection of at-risk drinking in a teaching hospital. AB - We studied a sample of 302 inpatients from all medical and surgical wards of Westmead Hospital. Twenty-six per cent of patients (47% of men and 4% of women) were identified as past or current "at-risk" drinkers. Current drinkers preponderantly were male and were more likely to be admitted to hospital with trauma. Apart from trauma, alcohol-related disease was not diagnosed commonly, and most drinkers were admitted to hospital with diagnoses that were not related clearly to alcohol abuse. Hospital medical staff members appeared reluctant to address alcohol abuse; a low rate of alcohol problems was identified, and alcohol related diseases appeared to be underdiagnosed. PMID- 2902510 TI - [The variability of arboviruses reproducing in vectors and their cell and tissue cultures]. PMID- 2902512 TI - [A reply to the doubts concerning the agent of AIDS]. PMID- 2902511 TI - [Chorea rheumatica. Clinico-therapeutic aspects of 13 cases]. PMID- 2902513 TI - Spontaneous reinnervation of a free muscle flap. AB - A latissimus dorsi muscle flap was used to repair a severe traumatic avulsion defect of the dorsum of the foot in a 3-year-old girl. The severed peroneal nerve apparently regenerated across a large gap and spontaneously reinnervated the denervated muscle flap. This resulted in a functional flap as demonstrated clinically and electromyographically. Surgical methods of muscle reinnervation and the influence of neurotrophic factors are discussed. PMID- 2902514 TI - Indications from animal and chemical experiments of a carcinogenic role for isobutyl nitrite. PMID- 2902515 TI - Altered T-cell helper/suppressor ratio in mice chronically exposed to amyl nitrite. PMID- 2902516 TI - Effects of nitrites on the immune system of humans. PMID- 2902517 TI - Resolution of quantitative traits into Mendelian factors by using a complete linkage map of restriction fragment length polymorphisms. AB - The conflict between the Mendelian theory of particulate inheritance and the observation of continuous variation for most traits in nature was resolved in the early 1900s by the concept that quantitative traits can result from segregation of multiple genes, modified by environmental effects. Although pioneering experiments showed that linkage could occasionally be detected to such quantitative trait loci (QTLs), accurate and systematic mapping of QTLs has not been possible because the inheritance of an entire genome could not be studied with genetic markers. The use of restriction fragment length polymorphisms (RFLPs) has made such investigations possible, at least in principle. Here, we report the first use of a complete RFLP linkage map to resolve quantitative traits into discrete Mendelian factors, in an interspecific back-cross of tomato. Applying new analytical methods, we mapped at least six QTLs controlling fruit mass, four QTLs for the concentration of soluble solids and five QTLs for fruit pH. This approach is broadly applicable to the genetic dissection of quantitative inheritance of physiological, morphological and behavioural traits in any higher plant or animal. PMID- 2902518 TI - [The value of screening and the national registration of hereditary tumors]. PMID- 2902519 TI - [Sharp decrease in the incidence of orchidopexy at Walcheren]. PMID- 2902520 TI - [A family with type 2a multiple endocrine neoplasms]. PMID- 2902521 TI - [Akathisia, a literature review]. PMID- 2902522 TI - [Possible mechanisms of strio-limbic integration in controlling the realization of an instrumental defense reflex in dogs]. PMID- 2902523 TI - Pressure wave with apnoea evaluated by sleep level in patient with ventricular dilation. AB - Seventeen patients who were suspected of having hydrocephalus, because of ventricular dilation from various causes, were included in this study of the pathophysiologic basis of the appearance of pressure waves (PWs). Pressure waves accompanied by apnoeas originated in arousal responses in the resting state of these patients. Frequent fits of apnoea were included in the entire sleep apnoea syndrome. Most pressure waves characteristically appeared in the state of non-REM sleep. During the appearance of such pressure oscillations, intracranial pressure was elevated transiently. This coincidence in the appearance of pressure oscillations with sleep apnoea was the most characteristic pathophysiologic result from this polygraphic study of the patients. PMID- 2902524 TI - Amino acid neurotransmitter levels in gliomas and their relationship to the incidence of epilepsy. AB - The cause of epilepsy due to gliomas is not known. Explanations that is due to mass effect, infiltration and site of the tumour appear insufficient. We have investigated the possibility that epilepsy due to gliomas is caused by interference with normal GABA and glutamate uptake and metabolism in the surrounding cortex. Analysis of human glioma biopsy specimens for the amino acid neurotransmitters and glutamine has shown that gliomas associated with epilepsy have a higher concentration of glutamine. This may be of importance since an elevated concentration of glutamine has been shown to be associated with the onset and severity of cobalt-induced epilepsy. PMID- 2902525 TI - Influence of the ipsilateral hemisphere upon somatosensory evoked potential in cats. AB - Somatosensory evoked potentials (SEPs) were recorded on the skull corresponding to the (left) SI area by (right) superficial radial nerve stimulation. Amongst the various components of the SEP, special attention was directed to the negative component (N15) with a latency of approximately 15 ms. Changes in this potential followed by conditioning stimulation of the ipsilateral (right) hemisphere were observed and the following results were obtained: (i) when conditioning stimuli were applied to the contralateral (left) superficial radial nerve, the ipsilateral (right) thalamic VPL nucleus and the ipsilateral (right) sensory cortex, the amplitude of N15 decreased to 65-80% of the control level at C-T intervals less than 100 ms and (ii) following functional elimination of the unilateral sensory cortex by KCl application, the amplitude of N15 recorded at the opposite side significantly increased. In this condition, the inhibitory effects of the ipsilateral thalamus and contralateral peripheral nerve disappeared. From these observations, ipsilateral homologous cortex may well have an inhibitory influence upon the near field potential (N15) of the SEP. PMID- 2902526 TI - Increase of plasma methionine-enkephalin levels in patients at the acute stage of cerebral infarction. AB - We investigated the participation of endogenous opioid peptide in cerebral ischaemia. In 13 patients with supratentorial infarction, the plasma immunoreactive methionine-enkephalin concentration at the acute stage (30.77 +/- 3.54 pg/ml) was significantly higher than that at the chronic stage (20.37 +/- 2.07 pg/ml) or that of the control subjects (19.64 +/- 1.71 pg/ml). However, it was unrelated to infarct size or patient severity. The increased methionine enkephalin, which appears to originate from the sympatho-adrenal system or infarcted brain, may play a role in the evolution of cerebral ischaemia. PMID- 2902527 TI - An epidural intracranial pressure monitor for experimental use in the rat. AB - We described the construction and use of a simple and reliable catheter system that can be used to monitor intracranial pressure (ICP) from the epidural space in rats in an experimental setting. The catheter system is easily fabricated in the laboratory from readily available materials. The monitor is fitted flush with the inner table through a burr hole in the temporal squama. A side port is used to fill the system with saline and to irrigate the system should be catheter become obstructed. The distal end of the catheter is fitted to a pressure transducer that is connected to a graphic display and recording system. This system was used to record ICP in 30 anaesthetized adult rats. Seven were subjected to baseline ICP recording only and 23 were subjected to baseline recordings followed by epidural balloon compression of the contralateral hemisphere. Baseline ICP varied between 0 and 8 mmHg and respiratory variation could be detected on the tracings for 24 rats (75%). ICP responded directly and sensitively to epidural balloon inflation in all 23 rats tested. In 5 rats that died during balloon inflation, the decrease in ICP after death followed closely the loss of arterial blood pressure. There was a close correlation of numerical values obtained in two rats in which ICP was recorded simultaneously from the epidural catheter and from a catheter in the subarachnoid space at the cisterna magna. In one rat in which ICP increased to more than 70 mmHg, the epidural catheter continued to record ICP accurately while the cisternal catheter became obstructed with herniated brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902528 TI - Early changes in cerebrospinal fluid Ca2+ and FFA levels following experimental spinal cord injury. AB - Cerebrospinal fluid (CSF) Ca2+ and free fatty acids (FFA) levels were determined for 4 h following experimental spinal cord (SC) injury in rabbits. The injury was produced by dropping a 20 g weight from 20 cm on exposed dura mater at the C5-C6 level. Samples of CSF were obtained from the cisterna magna from a second laminectomy at the C1 level. A significant decrease in CSF Ca2+ levels was observed 10 and 30 min post-injury; such levels increased above normal values 180 min post-injury. A significant increase in CSF FFA levels was seen from 10 to 240 min post-injury with a peak at 30 min. The early decrease of CSF Ca2+ levels and the concomitant increase in CSF FFA levels seem to confirm in role of Ca2+ in mediating the lipolytic response of the SC tissue to trauma. PMID- 2902529 TI - Evaluation of dead cases of ruptured intracranial aneurysms with special reference to a comparison between patients with early operations and unoperated cases. AB - The authors have analysed dead cases of ruptured intracranial aneurysms. This analysis included 270 patients with ruptured intracranial aneurysms, admitted to Mito National Hospital over an 8 yr period. Of the 98 patients who had surgery within 48 h after SAH, 17 cases died (mortality rate 17.3%); 7 deaths were due to massive haemorrhage, 5 due to vasospasm and 5 to other causes. Analysis of the causes of death in the non-surgical group (62 cases) disclosed that massive haemorrhage was the most common (29 cases), followed by rerupture after admission (14 cases), vasospasm (7 cases) and miscellaneous cases (5 cases). The possibility of improving the mortality rate in the early surgical group and the non-surgical group is discussed. PMID- 2902530 TI - The protective effect of mannitol, vitamin E and glucocorticoid on ischaemic brain injury: evaluation by chemiluminescence, energy metabolism and water content. AB - We currently have used three drugs in combination [mannitol, vitamin E and glucocorticoid (beta-methasone)] for the treatment of cerebral infarction in the acute stage. For the purpose of evaluating the efficacy of this therapy, we have conducted experiments evaluated by chemiluminescence (CL), energy metabolism and water content of the cortex using a global highly ischaemic rat brain. During the ischaemic period, CL levels increased with time and further increases were seen after recirculation of the blood flow. However, in the group which was administered the three drugs in combination, there was marked inhibition of CL value. Determination of adenine nucleotide and carbohydrate levels revealed that these drugs in combination promoted their recovery at the time of recirculation following ischaemia. In particular, the increase in lactate was inhibited during the ischaemia, thus preventing the progression of lactic acidosis. Moreover, in the group given all three drugs and in the group given 20% or isotonic mannitol, the increase in cortical water content following recirculation was inhibited. From these results it is deduced that these three drugs inhibit the cellular destruction by attenuation of free radical mediated peroxidation. PMID- 2902531 TI - Position sense in the lateral funiculus? AB - In recent years the traditional pathway for position sense in the lower extremities has been challenged and it has been proposed that in the upper spinal cord the relevant fibres ascend not in fasciculus gracilis but in the dorsolateral part of the lateral funiculus with the dorsal spinocerebellar tract. To determine whether this premise is correct we have re-examined the clinical findings of five patients with spinal cord lesions and 62 patients who had undergone medullary tractotomy at a level where the dorsal spinocerebellar tract overlies the spinal tract of V. Of the five patients with spinal cord lesions, four had interrupted dorsal columns but intact dorsal spinocerebellar tracts. They had a loss of position sense, vibratory sense and tactile discrimination. Another patient with a severed dorsal spinocerebellar tract and an incomplete lesion of the dorsal columns had no loss of position or vibratory sense but possibly some tactile impairment. None of the 62 medullary tractotomy patients had any loss of position, vibratory or tactile sensibility. These observations do not support the premise that position sense from the lower extremities is carried by fibres of the dorsal spinocerebellar tract at any level but do support the traditionally accepted pathway for position sense. Other papers that address this and related problems in humans are also reviewed. PMID- 2902532 TI - Effects of electrical stimulation on intracranial pressure and systemic arterial blood pressure in cats. Part I: Stimulation of brain stem. AB - It has been suggested that brain stem activity is involved in the occurrence of pressure waves. Different sites in the brain stem were activated by electrical stimulation in cats anaesthetized with sodium pentobarbital, to produce an increase in intracranial pressure (ICP) similar to the pressure waves. Then the effect of artificial ventilation on the occurrence of the pressure wave-like response produced under spontaneous respiration was examined since Lundberg's A waves appear even in artificial ventilation, and B-waves are effaced during artificial ventilation. This results in a brain stem map of ICP and systemic arterial blood pressure (BP) produced by electrical stimulation during spontaneous respiration. Stimulation of the rostral medullary reticular formation produced a rise in ICP and BP in association with a change in the rhythm of the spontaneous respiration; with artificial ventilation, stimulation produced a rise in BP but ICP kept almost at the same level. However, the rise in ICP that was produced by stimulation of the caudal medullary reticular formation during spontaneous respiration also occurred with a depressor response of BP during controlled ventilation. The pressure wave-like responses could be classified, therefore, into two types. One was the response seen during both spontaneous and controlled ventilation, which we designated the 'alpha' wave. The other was the response seen only during spontaneous ventilation, the 'beta' wave. These observations suggest that the origins of A- and B-waves may be related to those of 'alpha' and 'beta' waves, respectively. PMID- 2902533 TI - Effects of electrical stimulation on intracranial pressure and systemic arterial blood pressure in cats. Part II: Stimulation of cerebral cortex and hypothalamus. AB - This experimental work was carried out to examine whether activation of autonomic cortical and hypothalamic areas by electrical stimulation is related to changes in the intracranial pressure (ICP) in cats anaesthetized lightly with sodium pentobarbital. Electrical stimulation was performed using a concentric electrode with a train of electrical pulses (pulse duration, 0.4 ms; frequency, 40 Hz; intensity, 50-400 microA). Stimulation of sites in the anterior cingulate gyrus produced a rise in ICP associated with a fall in systemic arterial blood pressure (BP) or with no change in BP. Stimulation of sites in the anterior hypothalamus produced a fall in BP with an increase in ICP. Stimulation of sites in the area extending from the anterior hypothalamus to the posterior hypothalamus produced rises in BP and ICP. These observations suggest that activation of autonomic cortical and hypothalamic areas is involved in changes in ICP. PMID- 2902534 TI - The role of tissue acidosis in ischaemic tissue injury: the concept of the pH integral. AB - Cerebral cortical tissue pH was monitored with an extracellular glass electrode in 32 rats subjected to total global cerebral ischaemia produced by ligation of the basilar and carotid arteries with systemic hypotension for periods of 8 to 60 min. The totality of the ischaemia, and its duration were confirmed by monitoring with a brain tissue O2 electrode. Reperfusion was induced by hypertension and maintained thereafter to exclude delayed ischaemia during 3 h survival after which the rats were sacrificed by perfusion fixation. The severity of tissue pH change was varied by inducing hyperglycaemia in some of the rats. Quantitative counts were made of neurons demonstrating changes reflecting severe ischaemic injury within 500 microns of the electrode tip. For the criterion of an ischaemically injured neuron count greater than 20%, there appeared to be a threshold at about 30 min, and more than 0.8 units change in pH. For quantitative assessment of the ischaemic insult a more satisfactory index was found by combining both time and acidosis as the integral of the pH change during the period of ischaemia. This was found to have a strong correlation with the histologic changes. There was a less strong correlation between the acidosis during reperfusion and the histologic change. Comparing these results with those for 3 rats subjected to 215 min of ischaemia without reperfusion, it appears that most of the effect of acidosis in aggravating ischaemic injury takes place during the first hour of ischaemia with little further aggravation for longer periods. PMID- 2902536 TI - The role of the podiatrist in a wartime scenario. PMID- 2902535 TI - Concomitant increase of somatostatin, neuropeptide Y and glutamate decarboxylase in the frontal cortex of rats with decreased seizure threshold. AB - The neuropeptides somatostatin and neuropeptide Y and the activity of glutamate decarboxylase were determined in the frontal cortex of rats subjected to experimental epilepsy. Two different animal models, (1) rats kindled for 4 weeks by daily injection of pentylenetetrazole, and (2) rats which had undergone strong limbic seizures induced by kainic acid, were used. Decreased seizure threshold, as shown by injection of a subconvulsive dose of pentylenetetrazole, was observed 10 days after the last kindling session and 1 month after injection of kainic acid, respectively. Significantly increased levels of somatostatin (by 60%), neuropeptide Y (135%) and increased activity of glutamate decarboxylase (22%) were found in the frontal cortex of rats previously treated with kainic acid. Separation of somatostatin-like immunoreactivity by size exclusion high performance liquid chromatography showed a marked increase of immunoreactivity in fractions containing the somatostatin precursor (by 200%) and less prominently of somatostatin-14 and somatostatin-28 (by 60 and 80%, respectively). Michaelis Menten kinetics of glutamate decarboxylase revealed an increased maximal velocity (Vmax) in the frontal cortex of kainic acid-treated rats, but no change in the Km value was found. Similar results were also obtained in pentylenetetrazole-kindled rats. Injection of cysteamine (100 mg/kg, i.p.) resulting in a 30% decrease of cortical somatostatin in kainic acid-pretreated rats markedly suppressed seizures induced by an otherwise subconvulsive dose of pentylenetetrazole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902537 TI - [Use of citicoline in the study of chronic cerebrovascular diseases]. AB - Some of the disturbances encountered in patients with chronic cerebral vasculopathies may be attributable to associated or concomitant pathologies such as arterial hypertension. In many of the papers published on citicoline it is less than clear whether the improvement in the symptoms is the result of the treatment of the hypertension or the substance used. In conclusion, the importance of correct treatment of hypertension in order to cure certain standard chronic cerebral vasculopathies is emphasised and the value of citicoline in improving kinesthesis, mnemonic and perceptive-motor efficiency is confirmed. PMID- 2902538 TI - Intra-ischemic extracellular release of dopamine and glutamate is associated with striatal vulnerability to ischemia. AB - We have previously described a marked attenuation of postischemic striatal neuronal death by prior substantia nigra (SN) lesion, and have shown that lowering the brain temperature by only a few degrees during ischemia also confers a marked protective effect. The present study was carried out to evaluate whether the protective effect of these manipulations involves changes in extracellular release of striatal dopamine (DA) and glutamate (Glu) during ischemia. Four animal subgroups were investigated, including unilateral SN-lesioned rats whose intra-ischemic brain temperature was maintained at 36 degrees C, and non-lesioned animals whose brain temperature was not regulated, or was maintained at 33 or 36 degrees C during ischemia. Striatal extracellular sampling was performed by a microdialysis probe in rats subjected to 20 min of ischemia by 4-vessel occlusion. In rats whose intra-ischemic brain temperature was 36 degrees C, both DA and Glu increased significantly. In SN-lesioned rats no changes were found in extracellular levels of DA. However, significant increases in Glu were measured. In animals whose brain temperature was not regulated (the intra-ischemic brain temperature fell to 30 degrees C) or maintained at 33 degrees C there was a significant increase of DA release, but no changes were found in extracellular levels of Glu. These results, taken together with the neuropathological findings, suggest that release of both DA and Glu during ischemia is necessary for the development of postischemic striatal damage. PMID- 2902539 TI - Recent studies of the central nucleus of the amygdala and stress ulcers. AB - Studies are reviewed which indicate that the multiple-unit activity of the central nucleus of the amygdala differentiates stress-susceptible from stress resistant rats, highly emotional from less emotional animals, and genetically selected Roman High-Avoidance and Low-Avoidance rats. Kindling of this region increases the susceptibility to stress ulcer formation. Dopamine, neurotensin, and the endogenous opiates in the central nucleus are cytoprotective, whereas thyrotropin-releasing hormone aggravates the stress pathology. It is suggested that the amygdala codes the stressfulness of aversive inputs, the central nucleus being the point of output to areas controlling visceral responses to such information. PMID- 2902540 TI - Psychopharmacological effects in the radial-arm maze. AB - The radial-arm maze (RAM) has become a very widely used method for assessing spatial memory in rodents. It has proven to be quite useful in the investigation of the effects of a variety of pharmacological manipulations on spatial memory. The cholinergic system has been found to be crucial for accurate RAM performance. Blockade of either muscarinic or nicotinic receptors impairs performance. Other transmitter systems such as dopamine and the opiates have also been found to be involved with the maintenance of accurate RAM performance. This test has been found to be sensitive to the effects of a variety of toxicants given either in adulthood or during development. These findings provide a background for the assessment of the effects of novel substances on RAM performance as well as the basis for the further understanding of the neural substrates of memory. PMID- 2902541 TI - Comparative efficacy of two dopamine agonists, pergolide and lergotrile, in Parkinson disease. PMID- 2902542 TI - Laboratory determination of parentage. AB - By incorporating basic genetic concepts and assumptions, laboratories can determine if a man is excluded from paternity or, if not excluded, determine the likelihood of paternity. The concepts of exclusion and determination of likelihood of paternity are presented. PMID- 2902543 TI - [Hydrocortisone modification during intrauterine development of the activity of brain tyrosine hydroxylase in adult white rats]. AB - The activity of the key enzyme of catecholamine synthesis, tyrosine hydroxylase (TH), and the level of corticosteroids in blood were estimated in adult white rats in the normal state and after stress after their mothers were treated with hydrocortisone during pregnancy. The disturbance of the balance of corticosteroids during intrauterine development decreases the initial activity of TH in hypothalamus but increases it in the cortex of adult animals. Besides, after stress the increase in the level of corticosteroids in blood is less pronounced but the TH activation in hypothalamus is more distinct. Hence, the increase in the level of corticosteroids during intrauterine development induces long-term changes in the TH activity in brain which may be one of the causes of decrease in reactivity of adult animals after stress. PMID- 2902544 TI - Aphakic cystoid macular edema secondary to betaxolol therapy. AB - Since the approval of timolol for the treatment of open-angle glaucoma, beta adrenergic blocking drugs have replaced epinephrine, a pure alpha and beta agonist, as the treatment of choice for glaucoma in aphakic patients. To date, there have been no reports of cystoid macular edema secondary to timolol, a non selective beta-adrenergic blocker that apparently has little intrinsic sympathomimetic activity. Betaxolol is a new beta-adrenergic receptor blocker that preferentially blocks beta 1 receptors. We report a case of angiographically proven cystoid macular edema secondary to betaxolol therapy that resolved after discontinuation and recurred after a monocular therapeutic trial. PMID- 2902545 TI - The effect of Goldmann applanation tonometry on automated static threshold perimetry. AB - Automated static threshold perimetry was performed in both eyes of 10 normal and 12 ocular hypertensive subjects treated with a topical beta-blocker, before and after Goldmann applanation tonometry of their right eyes. Both objective statistical comparison and subjective evaluation of the resultant visual fields showed no detrimental effect on visual field test results after applanation tonometry. PMID- 2902546 TI - Modifying physician prescribing patterns of H2 receptor antagonists in an ambulatory setting. AB - Numerous studies have documented that primary care physicians prescribe H2 receptor antagonist medications for conditions other than those with approved indications. The Division of Ambulatory Care of the Maricopa County Department of Health Services used a three-physician review panel to confirm a similar prescribing pattern for these agents by physicians in its large ambulatory care system. Using current standards of practice as a guide, the panel determined that a change in physician prescribing patterns was necessary. Such modification was achieved through a comprehensive educational program. The new prescribing pattern resulted in a 10% reduction in the number of patients treated with H2 blockers and a 30% reduction in dosage and duration, for an estimated cost savings of $40,000 per year. PMID- 2902547 TI - [A method for reducing dislocations and fracture-dislocations of the foot]. PMID- 2902549 TI - [On the occasion of the reunion of medical writers at Siofok, 21-13 October 1988]. PMID- 2902548 TI - [Drugs that induce and/or worsen psoriasis]. PMID- 2902550 TI - [Experience in the use of salazopyrine EN in patients with spondylarthritis ankylopoietica and rheumatoid arthritis]. PMID- 2902551 TI - [Experimental validation of the use of alpha-adrenoblockers in combination with anticoagulants and fibrinolytic agents]. PMID- 2902552 TI - [Strong- and rapid-action regulator peptides]. PMID- 2902553 TI - Allergic rhinitis: recent advances. AB - Our understanding of the pathophysiology of allergic rhinitis is increasing as a result of the development of new research tools for investigation of patients with this disorder. The pharmacologic treatment of allergic rhinitis has been greatly improved by introduction of relatively nonsedating H1-receptor antagonists and potent, topically active, glucocorticosteroids. Immunotherapy for allergic rhinitis is also changing with the times. Patient selection criteria are becoming more strict, and the introduction of safer, modified allergens with decreased allergenicity and retained immunogenicity will be a major advance. PMID- 2902554 TI - Oxygen toxicity in the infant rhesus monkey: effects on regulatory peptides in lung and blood. AB - A total of ten 6-month-old male rhesus monkey (Macaca mulatta) infants, born full term, were positive-pressure ventilated with greater than 95% oxygen or room air (controls). A protocol was used which closely simulated pediatric intensive care. To test if regulatory peptides were affected by the oxygen treatment, and to search for an early marker of oxygen toxicity, lung tissue samples and systemic mixed venous blood were collected at 6, 12 and 24 hours after onset of treatment. The peptides, gastrin releasing peptide (GRP), calcitonin gene-related peptide (CGRP), peptide YY (PYY), vasoactive intestinal peptide (VIP) and somatostatin (SOM), were quantitated in lung tissue extracts and plasma using radioimmunoassay. Lung tissue GRP, CGRP, and PYY levels appeared to decrease gradually with time, perhaps as a result of the positive pressure ventilation procedure. GRP and CGRP levels decreased less among monkey infants ventilated with oxygen, thus they were significantly higher at 24 hours than in air ventilated controls. VIP levels were significantly lower among tests compared to controls at that time. Blood peptide levels did not change with oxygen treatment. These results suggest that tissue concentrations of certain pulmonary regulatory peptides can become altered by ventilation with greater than 95% oxygen. A blood borne peptide marker was not identified. PMID- 2902555 TI - The effect of postnatal development on the adherence of nonfimbriated and fimbriated Salmonella typhimurium to isolated small intestinal enterocytes. AB - The adherence of radiolabeled fimbriated (S 7471 OF) and nonfimbriated (S 7471 N) Salmonella typhimurium to small intestinal rat enterocytes was examined during postnatal development. The fimbriated strain invariably adhered in higher numbers than the nonfimbriated strain during all periods of development. The capability of enterocytes to bind Salmonella increased significantly during postnatal development and reached adult levels at weaning time (21 days of age). Bacterial adherence to enterocytes was similar if the cells were isolated from the proximal or the distal small intestine. Early weaning of pups did not affect the capability of enterocytes to bind Salmonella. Pretreatment of isolated enterocytes from adult animals with rat's milk before exposure to Salmonella had no effect on the level of bacteria that adhered per enterocyte. Conversely, pretreatment of Salmonella with rats' milk before binding to enterocytes from adult animals also did not alter the level of bacteria adhered per enterocyte. These results suggest an age-dependent, postnatal development of available receptors for S. typhimurium on rat enterocytes. The acquisition of these receptors is not affected by mother's milk and is unaltered by early weaning. PMID- 2902556 TI - Serologic diagnosis of whooping cough by enzyme-linked immunosorbent assay. AB - Pernasal swabs were obtained on 3 consecutive days from 146 children referred for hospital admission with suspected whooping cough, and immunoglobulin A and immunoglobulin M antibodies to Bordetella pertussis were measured by enzyme linked immunosorbent assay. The clinical features in 113 of the children were considered consistent with the diagnosis. Sixty-four cases were confirmed by serology, which showed a greater sensitivity (57% vs. 35%) than pernasal swab culture with no loss of specificity (100%). Paired serum samples were necessary for diagnosis in 30 (47%) of these 64 cases. Seventeen (43%) of 40 cases confirmed by pernasal swab culture had negative serologic results. Most of these were young infants who showed a less reliable antibody response. Detection of antibodies to B. pertussis by enzyme-linked immunosorbent assay can be a valuable additional test in the differential diagnosis of whooping cough but is not appropriate as the sole diagnostic test. PMID- 2902557 TI - Alpha 1-adrenergic regulation of Cl- and Ca2+ movements in rat parotid acinar cells. AB - In rat parotid acinar cells, maximal alpha 1-adrenergic receptor stimulation (10( 5) M epinephrine + 10(-5) M propranolol) leads to a rapid (less than 10 s), 4-5 fold elevation in cytosolic Ca2+ (approximately 800 nM at peak) which decreases to approximately 50% of peak Ca2+ by 3-4 min. Similarly, cells preloaded with 36Cl- show a rapid (less than 10 s) 35-50% loss of 36Cl- which returns to approximately 80% of resting values in 3-4 min. Both responses are dependent on epinephrine, with half-maximal effects achieved at 2 x 10(-7) M and 2 x 10(-6) M agonist for Cl- and Ca2+, respectively. In the presence of low extracellular Ca2+ (i.e. with EGTA), the initial rapid changes in cellular Ca2+ and Cl- are unaltered. However, cellular Ca2+ and Cl- levels return to basal values sooner than when extracellular Ca2+ is present (within approximately 2 and 3 min, respectively). Maximal epinephrine-induced Ca2+ and Cl- responses are unaffected by the alpha 2-adrenergic antagonist, yohimbine, are completely blocked by the alpha 1-adrenergic antagonist, SZL-49, and are similar to ion fluxes induced by maximal muscarinic-cholinergic receptor stimulation (10(-5) M carbachol). The data suggest that a close association exists between mobilization of intracellular Ca2+ and Cl- content in rat parotid acinar cells after alpha 1 adrenoceptor stimulation. PMID- 2902558 TI - A major antigen from Mycobacterium tuberculosis which is homologous to the heat shock proteins groES from E. coli and the htpA gene product of Coxiella burneti. PMID- 2902559 TI - Site-specific inversions in repeated Xenopus laevis homeobox gene 2 sequences. PMID- 2902560 TI - Eco RV RFLP at the insulin-like growth factor I (IGF I) locus on chromosome 12. PMID- 2902562 TI - Isolation and mapping of a polymorphic DNA sequence (lambda MC.34) on chromosome 2 [D2S63]. PMID- 2902561 TI - A DNA polymorphism with KpnI of the human liver-type phosphofructokinase (PFKL) gene. PMID- 2902563 TI - RFLP for TaqI of the human thyroid papillary carcinoma (PTC) oncogene. PMID- 2902564 TI - A Bgl II polymorphism detected by LDR152 [D19S19]. PMID- 2902565 TI - ACHF249 [D22S14] detects a common PstI RFLP and maps at 22cen----22q13.1. PMID- 2902566 TI - pACHF1.1 [D16S8] detects a common PvuII RFLP and maps at 16p13.3----16p13.11. PMID- 2902567 TI - RsaI and TaqI RFLPs for pACHF3.5 [D16S10]. PMID- 2902568 TI - RFLP and mapping of human MOX-1 gene on chromosome 3. PMID- 2902569 TI - BclI RFLP for the human vimentin gene. PMID- 2902570 TI - A TaqI RFLP identified at the retinoblastoma locus on chromosome 13. PMID- 2902571 TI - Dra I identifies a two allele DNA polymorphism in the human alpha 2-adrenergic receptor gene (ADRAR), using a 5.5 kb probe (p ADRAR). PMID- 2902572 TI - A BamHI RFLP at MT2A on human chromosome 16. PMID- 2902573 TI - RFLP for Duchenne muscular dystrophy cDNA clone 30-2. PMID- 2902575 TI - A frequent HindIII RFLP of the human fibronectin gene (FN1). PMID- 2902574 TI - EcoRI and NsiI RFLPs at a human PLA2 gene on chromosome 1. PMID- 2902576 TI - Strain polymorphism and tentative mapping of mouse ornithine decarboxylase. PMID- 2902578 TI - A three allele restriction fragment length polymorphism within the human Col2A1 gene. PMID- 2902577 TI - Two RFLPs in the 5' end of the human osteonectin (ON) gene. PMID- 2902579 TI - Further RFLPs at the human tyrosine hydroxylase locus. PMID- 2902581 TI - Isolation and mapping of a polymorphic DNA sequence (pEFD64.2) on chromosome 3 [D3S46]. PMID- 2902580 TI - Primary structure, developmentally regulated expression and potential duplication of the zebrafish homeobox gene ZF-21. AB - We report the molecular cloning and characterization of a cDNA derived from a zebrafish gene (ZF-21) related to the mouse homeobox containing gene Hox2.1. Interesting information about the differential conservation of various domains was gained from comparisons between the putative protein sequences from ZF-21 (275 amino acids) and Hox2.1 (279 aa). A separate DNA binding domain including the ZF-21 homeodomain and 36 additional flanking residues is completely identical to the C-terminal part of Hox2.1. As a consequence, these two mouse and zebrafish proteins must have identical DNA binding properties. A lower level of sequence identity between the N-terminal coding regions of ZF-21 and Hox2.1 reduces the total protein homology to 81%. However, short stretches of perfect homology in these N-terminals suggests that the essential biochemical functions are the same. As expected for true homologues, the ZF-21 and Hox2.1 genes also share extensive similarities with respect to non-coding sequences and temporal expression during embryogenesis. The finding of a potential ZF-21 duplication is discussed in relation to functional and evolutionary aspects of vertebrate homeobox genes. PMID- 2902582 TI - Isolation and mapping of a polymorphic DNA sequence (pEFD134.7) on chromosome 3 [D3S45]. PMID- 2902583 TI - Isolation and mapping of a polymorphic DNA sequence (cMCOD13) on chromosome 3 [D3S44]. PMID- 2902584 TI - Isolation and mapping of a polymorphic DNA sequence (pEFD145) on chromosome 3 [D3S32]. PMID- 2902585 TI - Isolation and mapping of a polymorphic DNA sequence (pMCT32.1) on chromosome 3 [D3S31]. PMID- 2902586 TI - Isolation and mapping of a polymorphic DNA sequence (pMCT106) on chromosome 2 [D2S61]. PMID- 2902587 TI - Isolation and mapping of a polymorphic DNA sequence (pEFZ38) on chromosome 2 [D2S60]. PMID- 2902588 TI - Isolation and mapping of a polymorphic DNA sequence (pCMM63) on chromosome 2 [D2S51]. PMID- 2902589 TI - Isolation and mapping of a polymorphic DNA sequence (cYNA4) on chromosome 2 [D2S50]. PMID- 2902590 TI - Isolation and mapping of a polymorphic DNA sequence (pTHH33) on chromosome 1q [D1S81]. PMID- 2902591 TI - Isolation and mapping of a polymorphic DNA sequence (pMCT118) on chromosome 1p [D1S80]. PMID- 2902592 TI - Isolation and mapping of a polymorphic DNA sequence (pCMM8) on chromosome 1p [D1S79]. PMID- 2902593 TI - Isolation and mapping of a polymorphic DNA sequence (pMHZ5) on chromosome 1 [D1S78]. PMID- 2902594 TI - Isolation and mapping of a polymorphic DNA sequence (pMCT58) on chromosome 1p [D1S77]. PMID- 2902595 TI - Isolation and mapping of a polymorphic DNA sequence (pCMM12) on chromosome 1p [D1S76]. PMID- 2902596 TI - Isolation and mapping of a polymorphic DNA sequence (cYNA13) on chromosome 1 [D1S74]. PMID- 2902597 TI - Isolation and mapping of a polymorphic DNA sequence (pCMM8.1) on chromosome 1p [D1S63]. PMID- 2902598 TI - RFLPs for the human pepsinogen A haplotypes (PGA). PMID- 2902599 TI - RFLP for the human pepsinogen C gene (PGC). PMID- 2902600 TI - HindIII RFLP on chromosome 8 detected with a calbindin 27 kDa cDNA probe, HBSC21. PMID- 2902601 TI - [Procaterol in the prevention of recurrent asthmatic bronchitis. Double-blind study]. AB - In a study in double-blind it has considered if the procaterol, given for a month, had been able to develop a preventive action in children affected from relapsing asthmatic bronchitis. For that the clinical symptomatology, the number of the contagious events and the consumption of the drugs have been valued for two following months. The patients who had taken the procaterol, presented a reduction of the contagious events, of the consumption of the drugs and of the spastic bronchus symptomatology in the first month of the treatment which continued in the second month. In spite of the development of the contagious events, in the third month, the pulmonary symptomatology resulted inferior in comparison with the group of check. It is likely than the treatment with procaterol avoids the arisen of the spastic-bronchus symptomatology for a rise of the threshold of bronchial re-established, consequent to the re-establishment of the mucous lesions. PMID- 2902602 TI - Controlled beta-receptor blockade with esmolol and flestolol. AB - Beta-receptor-blocking agents are commonly used in the management of various cardiovascular diseases. Recently, esmolol, a pharmacokinetically novel cardioselective beta-receptor-blocking agent, has been introduced for use in the treatment of critically ill patients. It is devoid of intrinsic sympathomimetic activity and in doses used clinically, it has no direct depressant effect on the heart. Esmolol is an ester and is metabolized by choline-esterase to ASL 8123, an inactive molecule. Esmolol has an elimination half-life of nine minutes which accounts for its ultrashort duration of action. This unique pharmacokinetic property provides two advantages over other longer-acting beta-receptor-blocking agents. First, the magnitude of beta-receptor blockade can be titrated to a desired level. Second, if adverse effects are experienced, reducing the dosage or terminating the infusion results in rapid reversal of its pharmacological effects. Another ultrashort-acting, non-cardioselective beta-receptor blocking agent, flestolol is undergoing clinical evaluation. Esmolol has been approved for the management of supraventricular tachycardia. The clinical safety of these novel drugs will expand the use of beta-receptor-blocking agents in the management of cardiovascular diseases in critically ill patients. PMID- 2902603 TI - Sleep disturbances in various nonaffective psychiatric disorders. AB - This article reviews electroencephalographic sleep studies in schizophrenia, obsessive-compulsive disorder, eating disorders, panic disorder, borderline personality disorder, Alzheimer's disease, and certain instances of substance abuse. PMID- 2902604 TI - Narcolepsy. Diagnosis, treatment, and management. AB - Narcolepsy is a syndrome of unknown origin characterized by the irresistible urge to sleep. Other important features are disturbed nocturnal sleep and abnormal manifestations of REM sleep such as cataplexy, sleep paralysis, and abnormal sleep-onset REM periods. Narcolepsy is not a rare condition. With a prevalence between 2 and 10 per 10,000 individuals, it is about as common as multiple sclerosis. Like multiple sclerosis, narcolepsy can be disabling and have profound consequences for job capability, public safety, sense of self-worth, and social image. PMID- 2902605 TI - Advances in medical genetics: Huntington disease. PMID- 2902606 TI - Male fertility and the undescended testis in Down syndrome. How to counsel parents. AB - Evaluation of fertility in male patients with Down syndrome has generally revealed poor psychosexual adaptation and markedly abnormal semen quality, which have thus far been uniformly associated with sterility. Up to 50% of male patients with Down syndrome have undescended testes. Life-table analysis of survival among patients with Down syndrome, as well as the low incidence of testicular tumors, would suggest that orchidopexy may be unnecessary in some patients. In most patients, however, orchidopexy is appropriate to allow for subsequent testicular examination. Parents of children with Down syndrome must be appropriately counseled regarding the fertility of their children and the treatment options for cryptorchidism. PMID- 2902607 TI - [T4/T8 ratio in bronchoalveolar lavage fluid: sensitivity and specificity for the diagnosis of sarcoidosis]. PMID- 2902609 TI - [Treatment of nocturnal hypoxia in chronic obstructive bronchopneumopathies]. PMID- 2902608 TI - [Comparative studies on the effectiveness of inhalant beta 2 mimetics therapy in patients with obstructive respiratory disorders]. PMID- 2902610 TI - [Lung function and blood gas analysis studies in patients with COPD and respiratory insufficiency receiving almitrine medication with special reference to its clinical aspects]. PMID- 2902611 TI - [Peripheral neuropathy in chronic bronchopathy. A study of 128 patients]. PMID- 2902612 TI - [The effect of almitrine dimesylate on pulmonary hemodynamics in healthy subjects and in patients with chronic obstructive bronchitis]. PMID- 2902613 TI - [Effect of almitrine, a chemoreceptor stimulator, on nocturnal hypercapnia and pulmonary artery pressure during O2 respiration in chronic obstructive lung disease]. PMID- 2902614 TI - [Periarteritis nodosa related to hepatitis B virus. Determination of a new therapeutic strategy: 13 cases]. AB - The treatment and prognosis of periarteritis nodosa associated with hepatitis B virus were reconsidered from a series of 13 patients representing 32.5 per cent of the 40 patients with periarteritis nodosa admitted during the same period. HBs and HBe antigens were present in every case, and hepatitis B virus replication was demonstrated by the finding of viral DNA in serum. One patient had anti-HBc IgM's. Five patients were treated with corticosteroids, cyclophosphamide and occasional plasma exchanges. All were cured or achieved complete remission. Eight patients were treated with plasma exchanges and vidarabine, either as first-line therapy (3 cases) or after failure of corticosteroids and/or immunosuppressants (5 cases). This treatment was clinically effective in 5/8 cases, including 3 with seroconversion. The 2 patients in whom the combined treatment failed were given corticosteroids; one of them also had plasma exchanges. The 8th patient died after a few days of treatment. Eleven of the 13 patients are still alive and either cured or in complete remission. Two patients who developed severe chronic hepatitis after steroids were discontinued received vidarabine alone: arrest of viral replication was obtained in both cases, with emergence of an anti-HBe (but not anti-HBs) antibody. The overall positive virological response rate to vidarabine alone or combined with plasma exchanges was 50 per cent. When vidarabine was prescribed as treatment of acute periarteritis nodosa (the 2 cases where it was used for chronic hepatitis being excluded), this response rate was 37.5 per cent. This, in patients with periarteritis nodosa associated with hepatitis B virus immunosuppressive drugs should be withdrawn and replaced by plasma exchanges and antiviral agents. This would be the first-line treatment to be replaced by corticosteroid therapy if it fails. PMID- 2902615 TI - [Superiority of a new etiopathogenic treatment curing periarteritis nodosa caused by hepatitis B virus, using a combination of brief corticotherapy, vidarabine and plasma exchange]. AB - A new physiopathological treatment of HBV-related polyarteritis inspired by advances in the treatment of chronic active hepatitis B was tested in 7 patients. The new protocol included short term corticosteroid therapy, a course of antiviral chemotherapy with vidarabine and repeated plasma exchanges enabling steroids to be discontinued after 2 weeks. This treatment was well tolerated, and 6 of the 7 patients treated were clinically, biologically and virologically cured. The eradication of HBV among the patients who were cured was confirmed by clearance of HBs Ag and its replacement by anti HBs. None of the 6 patients relapsed during a 2 to 7 years' follow-up. The seventh patient died. In contrast, no patient had been cured in a similar group of 7 polyarteritis patients previously treated with the conventional symptomatic therapy using corticosteroids (6/7), plasma exchanges (4/7) and immunosuppressants (2/7). The outcome in this older series followed up for 3 years was altogether unfavourable, with 3 deaths, 3 chronic forms with multiple relapses and 1 spontaneous stabilisation. All patients remained chronic carriers of HBV. These results suggest that the new aetiopathogenic treatment capable of curing polyarteritis patients should replace the classical symptomatic treatment as soon as these preliminary results are confirmed by those of a multicentre study in progress. PMID- 2902616 TI - [HTLV-1 in France]. PMID- 2902617 TI - [Treatment of pregnancy hypertension with betablockaders. Follow-up of 31 pregnancies]. PMID- 2902618 TI - [Isolation and purification of phospholipase C from Clostridium perfringens and antibodies against it using polymeric biospecific adsorbents]. AB - A new polymeric biospecific adsorbent intended for isolation of Clostridium perfringens phospholipase C (PLC) and PLC-specific antibodies is discussed. It was obtained by radical copolymerization of acrylamide, methylenbisacrylamide, and the acryl acid chloranhydride-acylated substrate of PLC (chicken yolk lecithovitellin). Maximal adsorption of PLC was observed in the presence of the enzyme activator, and the highest amount of PLC was eluted in case of its minimal adsorption. The "residual" activity of PLC on the adsorbent was used to isolate homologous antibodies from the anti-perfringens serum. PLC and PLC-specific antibodies were serologically pure in the agar precipitation test with the anti perfringens serum and the primary PLC concentrate, respectively; the antibodies gave only one zone in PAAG-electrophoresis. PMID- 2902619 TI - Somatostatin in pancreatic secretion. PMID- 2902620 TI - Secretion of protein, fluid, and immunoreactive somatostatin in rat pure pancreatic juice: adaptation to chronic cerulein and secretin treatment. AB - These studies were undertaken to assess the effects of chronic administration of cerulein plus secretin, every 8 h for 10 days on fluid, protein, and somatostatin like immunoreactivity (SLI) outputs in rat pancreatic juice. Pancreatic secretion was studied with conscious, cannulated rats, during infusion of precollected pancreatic juice to the rat intestine. Volume output reached a plateau of 5.2 ml/210 min after 3 days of treatment. Protein secretion steadily increased up to 218 mg/210 min after 5 days, decreased to 118 mg/210 min by day 7, and rose again to 281 mg/210 min after 10 days. The SLI release increased stepwise with a first plateau after 3 days at 493 ng/210 min; values between 983 and 562 ng/210 min were observed between days 4 and 7 with a third plateau at 1,887 ng/210 min between days 8 and 10. Peak levels of volume and protein occurred between 30 and 90 min following each daily stimulation. In the early days SLI output reached its peak 3.5 h after stimulation, whereas at the end of treatment, synchronous secretion of protein and SLI was observed. These data indicate that important modifications occur in the rate of secretion of protein and SLI in the pancreatic juice in the course of chronic administration of cerulein plus secretin. PMID- 2902621 TI - Mechanisms of terbutaline-induced inhibition of exocrine pancreatic secretion in humans. AB - Terbutaline, a selective beta 2-adrenoreceptor agonist, has recently been advocated as a potential agent for treating patients with pancreatic fistulae. In the present study, we attempted to quantify the presumed effects of terbutaline on exocrine pancreatic secretion in humans and to characterize possible mechanisms of action. In six healthy volunteers, the pancreas was stimulated by infusion of graded doses of secretin (15.5-250 ng/kg/h) or by infusion of secretin (15.5 ng/kg/h) plus graded doses of caerulein (3.3-30 ng/kg/h). The experiments were repeated in each subject without and with administration of terbutaline. Pancreatic secretion was assessed by a marker perfusion technique and plasma somatostatin and pancreatic polypeptide (PP) levels by radioimmunoassay. Terbutaline had no significant effect on secretin-stimulated pancreatic secretion, but significantly inhibited caerulein-stimulated pancreatic fluid secretion and trypsin output. Plasma somatostatin and PP levels were not affected by terbutaline. The inhibitory effect required the administration of pharmacologically large doses of terbutaline. We conclude that the weak inhibitory effect of terbutaline on exocrine pancreatic secretion is not mediated via somatostatin nor PP and that our data do not support a major role for beta adrenergic mechanism as regulator of pancreatic secretion. PMID- 2902622 TI - The possible role of dopamine autoreceptors in neuroleptic atypicality. AB - Different brain pathways have been shown to subserve the therapeutic effects of neuroleptics and their extrapyramidal side effects. Agents which can discriminate between these pathways, therefore, might be able to produce 'atypical' clinical effects. Molindone, a novel neuroleptic of the indoleamine class, has been shown in basic paradigms to discriminate between brain dopaminergic systems by virtue of its ability to preferentially inhibit dopamine autoreceptors (DARs). Clinical studies suggest that molindone may be less likely than traditional neuroleptics to induce tardive dyskinesia and that molindone may preferentially ameliorate some negative schizophrenic symptoms. We suggest that the distinct clinical effects of molindone result from its ability to block DARs. PMID- 2902623 TI - Molecular cloning of cDNA coding for brain-specific 14-3-3 protein, a protein kinase-dependent activator of tyrosine and tryptophan hydroxylases. AB - The 14-3-3 protein is a family of acidic proteins present exclusively in the brain and is believed to have a function in monoamine biosynthesis because of its ability to activate tyrosine hydroxylase and tryptophan hydroxylase in the presence of Ca2+/calmodulin-dependent protein kinase type II. In this study, we resolved bovine brain 14-3-3 protein into seven polypeptide components by means of reversed-phase chromatography and determined the amino acid sequence of one of these components (eta chain) by cloning its cDNA from a bovine cerebellum cDNA library. The eta-chain mRNA is 1.8 kilobases long and encodes a polypeptide of 246 amino acids and Mr 28,221. Computer-assisted analysis of the sequence indicates that the eta chain exhibits no internal sequence repeats, nor does it have significant sequence similarity to other proteins with known amino acid sequence. However, the eta chain appears to consist of two structural regions that are distinguishable in their clearly different charge characteristics: the almost neutral amino-terminal region and the strongly acidic carboxyl-terminal region. The structural features of the eta chain and the domain organization of tyrosine and tryptophan hydroxylases suggest that the 14-3-3 protein binds to the regulatory domain of the phosphorylated hydroxylases through its acidic carboxyl terminal region and activates the hydroxylases by inducing an active conformation. PMID- 2902624 TI - An evolutionarily conserved protein binding sequence upstream of a plant light regulated gene. AB - A protein factor, identified in nuclear extracts obtained from tomato (Lycopersicon esculentum, Solanaceae) and Arabidopsis thaliana (Brassicaceae) seedlings, specifically binds upstream sequences from the plant light-regulated gene family encoding the small subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase (RBCS). RBCS upstream sequences from tomato, pea (Pisum sativum, Leguminosae), and Arabidopsis are recognized by the factor. The factor recognition occurs via a short conserved sequence (G box) whose consensus sequence is 5'-TCTTACACGTGGCAYY-3' (where Y is pyrimidine). This sequence is distinct from the GT motif described previously in RBCS promoters. Two other conserved sequences, showing a lesser degree of evolutionary conservation, are found upstream of the G box but do not bind to the G box binding factor (GBF). Twelve nucleotides within the G box are sufficient for the formation of a stable DNA-GBF complex. GBF is found in both light-grown and dark-adapted tomato leaf extracts, but it is present in greatly reduced amounts in root extracts. PMID- 2902625 TI - Photoaffinity labeling of the multidrug-resistance-related P-glycoprotein with photoactive analogs of verapamil. AB - Verapamil, a phenylalkylamine calcium channel blocker, has been shown to reverse multidrug resistance in tumor cells, possibly by increasing drug retention through interaction with an outward drug transporter of the resistant cells. In this study two photoactive radioactive analogs of verapamil, N-(p-azido[3,5 3H]benzoyl)aminomethyl verapamil and N-(p-azido[3-125I]salicyl)aminomethyl verapamil, were synthesized and used to identify the possible biochemical target(s) for verapamil in multidrug-resistant DC-3F/VCRd-5L Chinese hamster lung cells selected for resistance to vincristine. The results show that a specifically labeled 150- to 180-kDa membrane protein in resistant cells was immunoprecipitated with a monoclonal antibody specific for P-glycoprotein. Phenylalkylamine binding specificity was established by competitive blocking of specific photolabeling with the nonradioactive photoactive analogs as well as with verapamil. Photoaffinity labeling was also inhibited by 50 microM concentrations of the calcium channel blockers nimodipine, nifedipine, nicardipine, azidopine, bepridil, and diltiazem and partially by prenylamine. Bay K8644, a calcium channel agonist, also inhibited P-glycoprotein photolabeling. Moreover, P-glycoprotein labeling was inhibited in a dose-dependent manner by vinblastine with half-maximal inhibition at 0.2 microM compared to that by verapamil at 8 microM. Photolabeling was also partially inhibited by two of the drugs to which these cells are cross-resistant, doxorubicin and actinomycin D, at 100 microM, but not by colchicine. These data provide direct evidence that P glycoprotein has broad drug recognition capacity and that it serves as a molecular target for calcium channel blocker action in reversing multidrug resistance. PMID- 2902626 TI - Cyclic AMP induction of early adenovirus promoters involves sequences required for E1A trans-activation. AB - Early in adenovirus infection, the E1A (early region 1A) oncogene products trans activate the other early viral transcription units, as well as some cellular promoters. The mechanism by which E1A elicits its activity is still unknown. In this report, I show that the adenovirus E2a and E3 promoters are cAMP inducible in rat pheochromocytoma PC12 cells and that this activation requires the presence of the cAMP-dependent protein kinase II. Using deletion mutants of the E2a promoter, it was found that the sequence TACGTCAT located between positions -70 and -77 is involved in both the cAMP response and the E1A trans-activation. Also, in the mutant PC12 cell line A126-2B, which lacks the cAMP-dependent protein kinase II, E1A is still able to activate E2a and E3 promoters. This suggests that E1A products may circumvent the lack of the kinase by activating an alternative signal transduction pathway, which could mimic the effect of agonists of adenylate cyclase. I propose that E1A is capable of modifying by phosphorylation, either directly or indirectly, the transcription factor that binds the ACGTCA motif. Such a factor, termed ATF (adenovirus transcription factor), has already been characterized and appears to have strong similarities to the transcriptional factor CREB (cAMP responsive element binding protein), which binds homologous sequences in cAMP responsive genes, such as somatostatin and c-fos. PMID- 2902627 TI - Coordinate regulation of two genes encoding gluconeogenic enzymes by the trans dominant locus Tse-1. AB - Tissue-specific extinguisher-1 (Tse-1) is a mouse genetic locus that can repress liver-specific tyrosine aminotransferase gene expression in trans. To search for other Tse-1-responsive genes, hepatoma microcell hybrids retaining mouse chromosome 11 or human chromosome 17, containing murine Tse-1 and human TSE1, respectively, were screened for expression of liver-specific mRNAs. While most liver gene activity was unaffected in such hybrids, phosphoenolpyruvate carboxykinase and tyrosine aminotransferase gene expression was coordinately repressed in these clones. Extinction of both genes was apparently mediated by a single genetic locus that resides on human chromosome 17. PMID- 2902628 TI - Gangliosides prevent glutamate and kainate neurotoxicity in primary neuronal cultures of neonatal rat cerebellum and cortex. AB - Using a sensitive histofluorescence staining method that allows for a quantitation of neuronal death, we compared the protective effects of gangliosides (a group of naturally occurring glycosphingolipids), phencyclidine (PCP), and MK-801 (dibenzocyclohepteneimine) on glutamate- and kainate-induced neuronal death in primary cultures of cortical and cerebellar neurons prepared from neonatal rats. PCP and MK-801 block neurotoxicity induced by glutamate doses 50 times higher than the LD50 (LD50 in Mg2+-free medium, 10 microM) but only partially block the kainate neurotoxicity (LD50 in presence of Mg2+, 100 microM). In contrast, pretreatment with gangliosides (GT1b greater than GD1b greater than GM1) results in complete and insurmountable protection against the neurotoxicity elicited by glutamate or kainate. In primary cultures of cerebellar granule cells gangliosides, unlike PCP and MK-801, fail to block glutamate-gated cationic currents and the glutamate-evoked increase of (i) inositol phospholipid hydrolysis (ii) c-fos mRNA content, and (iii) nuclear accumulation of c-fos protein. Protection of glutamate neurotoxicity by gangliosides does not require their presence in the incubation medium; however, it is proportional to the amount of glycosphingolipid accumulated in the neuronal membranes. The ganglioside concentration (30-60 microM) that blocks glutamate-elicited neuronal death also prevents glutamate- and kainate-induced protein kinase C translocation from cytosol to neuronal membranes. PMID- 2902629 TI - Immunoglobulins from amyotrophic lateral sclerosis patients enhance spontaneous transmitter release from motor-nerve terminals. AB - Amyotrophic lateral sclerosis (ALS) is an incapacitating neuromuscular disease of unknown etiology. Although laboratory evidence is lacking, circumstantial evidence supports the importance of immune factors in the pathogenesis of ALS. In the present study immunoglobulins from 4 of 8 ALS patients induced a significant increase in spontaneous quantal transmitter release as monitored by miniature end plate potential (MEPP) frequency in mouse phrenic nerve-diaphragm preparations at 23 degrees C, whereas immunoglobulins from normal individuals and from patients with other neuromuscular diseases had no effect. At 32 degrees C neither normal nor disease control immunoglobulins influenced MEPP frequency, but 8 of 11 ALS immunoglobulin samples produced a significant increase in spontaneous quantal transmitter release. The enhancing effect could be prevented by 10 mM Mg2+. No effects were noted on MEPP amplitude and muscle resting potential. These findings suggest that the presynaptic terminal of the motor neuron may be an early target and that immunological factors may play an important role in the disease process. PMID- 2902630 TI - "DAKLI": a multipurpose ligand with high affinity and selectivity for dynorphin (kappa opioid) binding sites. AB - We describe a synthetic ligand, "DAKLI" (Dynorphin A-analogue Kappa LIgand), related to the opioid peptide dynorphin A. A single reactive amino group at the extended carboxyl terminus permits various reporter groups to be attached, such as 125I-labeled Bolton-Hunter reagent, fluorescein isothiocyanate, or biotin. These derivatives have high affinity and selectivity for the dynorphin (kappa opioid) receptor. An incidental finding is that untreated guinea pig brain membranes have saturable avidin binding sites. PMID- 2902631 TI - The yeast analog of mammalian cyclin/proliferating-cell nuclear antigen interacts with mammalian DNA polymerase delta. AB - DNA polymerase III from Saccharomyces cerevisiae is analogous to the mammalian DNA polymerase delta by several criteria, including an increased synthetic activity on poly(dA).oligo(dT) (40:1 nucleotide ratio) in the presence of calf thymus proliferating-cell nuclear antigen (PCNA), or cyclin. This stimulation assay has been used to purify the yeast analog of PCNA/cyclin (yPCNA) to homogeneity. yPCNA is a trimer or tetramer (Mr approximately 82,000) of identical subunits with a denatured Mr of 26,000. On a molar basis yPCNA and calf thymus PCNA/cyclin are equally active in stimulating DNA synthesis by DNA polymerase III. About 10 times more yPCNA than calf thymus PCNA/cyclin is needed, however, to stimulate calf thymus DNA polymerase delta, and the degree of stimulation obtained at saturating levels of yPCNA is a factor of 2-3 less than with calf thymus PCNA/cyclin. Both stimulatory proteins exert their effect in an identical fashion, i.e., by increasing the processivity of the DNA polymerase. Yeast DNA polymerases I and II and calf thymus DNA polymerase alpha are not stimulated by yPCNA. Treatment of logarithmic-phase cells with hydroxyurea blocks them in the S phase and produces a 4- to 5-fold increase in yPCNA. PMID- 2902632 TI - Subunit S1 of pertussis toxin: mapping of the regions essential for ADP ribosyltransferase activity. AB - The toxicity of pertussis toxin is mediated by the ADP-ribosyltransferase activity of subunit S1. To understand the structure-function relationship of subunit S1 and guide the construction of nontoxic molecules suitable for vaccines, we constructed and expressed in Escherichia coli a series of amino terminal and carboxyl-terminal deletion mutants as well as a number of molecules containing amino acid substitutions. The shortest peptide still retaining enzymatic activity contains amino acids 2-179. Within this region we identified three mutants in which amino acid substitutions abolish the enzymatic activity. Mutation of amino acids 8 and 9 or 50 and 53, located within the region of the S1 subunit of pertussis toxin homologous to cholera toxin, causes loss of enzymatic activity. Outside this homology region, substitution of Glu-129 with glycine or aspartic acid also eliminates the enzymatic activity of the S1 subunit. In this respect, Glu-129 resembles the glutamic acid that is crucial for the catalytic activity of diphtheria and Pseudomonas toxins. Once introduced into the Bordetella pertussis chromosome, the above mutations should lead to the synthesis of nontoxic pertussis toxin molecules suitable for vaccine production. PMID- 2902633 TI - Genetic determinants of neoplastic transformation by the retroviral oncogene v erbB. AB - The retroviral oncogene v-erbB is a mutant version of the gene (c-erbB or ERBB1) that encodes the cell-surface epidermal growth factor receptor (EGFR). The mutations take three forms: (i) a large deletion that removes the entire ligand binding domain of EGFR, (ii) smaller deletions that affect the carboxyl-terminal domain of EGFR, and (iii) point mutations that cause conservative substitutions of amino acids. Previous work has shown that, in the absence of the large deletion, ERBB1 cannot transform cells autonomously. Here we report that when the large deletion is present, no other mutation is required for ERBB1 to transform established rodent fibroblasts to a tumorigenic phenotype. In particular, there is no need for deletions affecting the carboxyl terminus of the gene product. It appears, therefore, that removal of the ligand-binding domain from the EGFR suffices to create a transforming protein. Deletions at the carboxyl terminus of the EGFR apparently play only a secondary role in transformation by affecting the host range and perhaps the potency of transformation; and there is as yet no evidence to implicate point mutations in the activation of ERBB1 to an oncogene. Our findings support the view that augmented activity of the EGFR can contribute to tumorigenesis. PMID- 2902634 TI - Chromosomal localization of genes encoding guanine nucleotide-binding protein subunits in mouse and human. AB - A variety of genes have been identified that specify the synthesis of the components of guanine nucleotide-binding proteins (G proteins). Eight different guanine nucleotide-binding alpha-subunit proteins, two different beta subunits, and one gamma subunit have been described. Hybridization of cDNA clones with DNA from human-mouse somatic cell hybrids was used to assign many of these genes to human chromosomes. The retinal-specific transducin subunit genes GNAT1 and GNAT2 were on chromosomes 3 and 1; GNAI1, GNAI2, and GNAI3 were assigned to chromosomes 7, 3, and 1, respectively; GNAZ and GNAS were found on chromosomes 22 and 20. The beta subunits were also assigned--GNB1 to chromosome 1 and GNB2 to chromosome 7. Restriction fragment length polymorphisms were used to map the homologues of some of these genes in the mouse. GNAT1 and GNAI2 were found to map adjacent to each other on mouse chromosome 9 and GNAT2 was mapped on chromosome 17. The mouse GNB1 gene was assigned to chromosome 19. These mapping assignments will be useful in defining the extent of the G alpha gene family and may help in attempts to correlate specific genetic diseases with genes corresponding to G proteins. PMID- 2902635 TI - Human ETS2 gene on chromosome 21 is not rearranged in Alzheimer disease. AB - The human ETS2 gene, a member of the ETS gene family, with sequence homology with the retroviral ets sequence of the avian erythroblastosis retrovirus E26 is located on chromosome 21. Molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 allowed us to reinforce the supposition that ETS2 may be a gene of the minimal DS genetic region. It was originally proposed that a duplication of a portion of the DS region represents the genetic basis of Alzheimer disease, a condition associated also with DS. No evidence of either rearrangements or duplications of ETS2 could be detected in DNA from fibroblasts and brain tissue of Alzheimer disease patients with either the sporadic or the familiar form of the disease. Thus, an altered ETS2 gene dosage does not seem to be a genetic cause or component of Alzheimer disease. PMID- 2902636 TI - Pst I restriction fragment length polymorphism of human placental alkaline phosphatase gene: Mendelian segregation and localization of mutation site in the gene. AB - The pattern of inheritance of a Pst I restriction fragment length polymorphism (RFLP) of the human placental alkaline phosphatase gene was studied in nine nuclear families by Southern blot hybridization analysis of genomic DNA. The dimorphic RFLP is defined by the presence of allelic fragments 1.0 kilobase and 0.8 kilobase long. The results of this study show that the two alleles of the PstI RFLP of the placental alkaline phosphatase gene segregate as codominant traits according to Mendelian expectations. For a polymorphism to be useful as a genetic marker the probability that an offspring is informative (PIC) must be at least 0.15. The allelic frequency of the 1.0-kilobase allele is 0.21, which correlates to a probability that an offspring is informative of 0.275 and is indicative of a useful polymorphism. By using probes derived from different regions of the placental alkaline phosphatase cDNA, the mutated Pst I site causing the RFLP was located in the penultimate intron 2497 base pairs downstream from the transcriptional initiation site. PMID- 2902637 TI - A primate species with limited major histocompatibility complex class I polymorphism. AB - Extensive polymorphism at the major histo-compatibility complex (MHC) is thought to confer immune protection on populations. A New World primate, the cotton-top tamarin (Saguinus oedipus), has a high prevalence of ulcerative colitis and adenocarcinoma of the colon and dies after infection with several human viruses. Lymphocytes from all animals tested expressed on common MHC class I allelic product. Another MHC class I allelic product was expressed by 39 of 41 tested animals. Four other allelic products were also expressed on the lymphocytes of these animals at a frequency of greater than 50%. MHC class II gene products, however, were polymorphic. Restriction fragment length polymorphism analysis confirmed that there were a limited number of cotton-top tamarin MHC class I alleles, whereas the MHC class II gene loci were polymorphic. This sharing of MHC class I alleles is unprecedented in a higher primate species and may play a role in the susceptibility of this endangered species to pathogens. PMID- 2902638 TI - T-cell receptor alpha-chain variable-region haplotypes of normal and autoimmune laboratory mouse strains. AB - We used Southern blotting and mRNA analysis to characterize allelic polymorphisms among genes of the T-cell antigen receptor (TCR) alpha-chain variable-region (V alpha) locus in a large panel of normal and autoimmune-susceptible or autoimmune contributing strains of laboratory mice. Four major V alpha haplotypes were defined on the basis of multiple restriction fragment length polymorphisms for each of nine V alpha subfamily probes used. Southern blotting also revealed haplotype-specific loss of bands within some V alpha subfamilies, consistent with the deletion of particular V alpha genes or sets of genes from haplotype to haplotype. In contrast to the situation in the V beta locus, however, deletion of entire V alpha subfamilies was not observed. The nature of V alpha allelic variability was further explored by using an RNase protection assay to analyze expressed V alpha mRNA sequences in thymocyte RNA. Such analysis revealed both shared and unique patterns of V alpha mRNA expression among the different haplotypes and supported the conclusion that haplotype differences sometimes involve V alpha gene deletions. Interestingly, a disproportionate number of, but not all, autoimmune-susceptible strains, including NZB, SJL, SWR, PL/J, and NOD, share a common V alpha haplotype. The identification of murine TCR V alpha haplotypes should provide a basis for understanding the role of TCR diversity in normal immunoregulatory and immune-response phenomena, as well as autoimmune disease predisposition. PMID- 2902639 TI - Evolutionary genetics of the encapsulated strains of Haemophilus influenzae. AB - Genetic relationships among 2209 isolates of Haemophilus influenzae of polysaccharide capsule serotypes a, b, c, d, e, and f were determined by analyzing electrophoretically demonstrable allelic variation at 17 chromosomal enzyme loci. We distinguished 280 electrophoretic types (ETs), representing distinctive multilocus genotypes. Genetic diversity among ETs of isolates of the same serotype was, on average, only 67% of that in the total sample, and no ETs were shared among isolates of different serotypes. Cluster analysis of the ETs revealed 2 primary phylogenetic divisions at a genetic distance of 0.66 and 12 major lineages diverging from one another at distances greater than 0.42. In general, strains of different phylogenetic lines or groups of allied lineages have characteristic cap region restriction fragment length polymorphism patterns obtained by digestion of genomic DNA with EcoRI. Strains producing serotype c, e, and f capsules have no close relationships to those of other encapsulated strains. Lineages of both serotype a and b strains occur in each primary phylogenetic division, most probably as a result of the transfer of serotype specific sequences of the cap region between clonal lineages. Serotype a strains allied in division I with a group of abundant serotype b clones and the serotype d strains apparently are more virulent than the serotype a strains in division II, which are related to serotype b and f strains that rarely cause invasive disease. PMID- 2902640 TI - Uses of calcium channel blocking agents and beta blocking agents in the control of supraventricular arrhythmias. PMID- 2902641 TI - P-glycoprotein gene amplification or overexpression is not detected in clinical breast cancer specimens. PMID- 2902642 TI - Zuclopenthixol decanoate in the management of behavioural disorders in mentally handicapped patients. AB - One hundred and sixteen mentally handicapped patients with behavioural disorders were studied in a double-blind clinical comparison of zuclopenthixol decanoate injection (mean dosage 123 mg/week) and placebo. The study consisted of a 4-week open phase, in which all patients were treated with zuclopenthixol decanoate, followed by a 12-week double-blind phase where approximately half of the patients were changed to placebo. Patients were assessed every 2 weeks using the Clinical Global Impression, the Nurse's Observation Scale for In-patient Evaluation, a specific behaviour rating scale designed for this study and a side-effects check list. Fourteen patients in the placebo group were withdrawn because of an increase in the frequency and severity of their behavioural disorders compared to only 4 in the zuclopenthixol decanoate group. Analyses of the rating scales of the patients remaining in the study also showed zuclopenthixol decanoate to be superior to placebo in the treatment of mentally handicapped patients with behavioural disorders. Side-effects in general were not a problem and did not affect treatment. PMID- 2902643 TI - Codeine produces a cholinergically mediated analeptic effect in rats and rabbits. AB - The intravenous administration of codeine to diazepam-narcotized rabbits resulted in a shortened duration of loss of righting reflex. Coadministration of naltrexone plus codeine enhanced this analeptic effect and was also effective in shortening the duration of pentobarbital narcosis. The analeptic effect was blocked by atropine, but not by methylatropine, indicating involvement of a central cholinergic mechanism. In rats the analeptic activity correlated with the reversal of the diazepam-induced fall in sodium dependent high affinity choline uptake in hippocampal and cortical synaptosomes. These findings may represent the pharmacological basis of the recently reported antinarcoleptic action of codeine in man. PMID- 2902644 TI - Is stimulation of both D1 and D2 receptors necessary for the expression of dopamine-mediated behaviors? AB - Recent electrophysiological findings have indicated that D1 dopamine (DA) receptor stimulation by SKF 38393 enables the inhibitory effects of the D2 receptor agonist quinpirole on nucleus accumbens neurons. In the present study, a similar interaction was shown for quinpirole-induced stereotyped behaviors. In control rats, SKF 38393 enhanced the stereotyped responses induced by quinpirole, converting lower-level stereotypies (sniffing and rearing) to more intense oral behaviors (licking and gnawing). In rats depleted of DA (79% reduction) by the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMPT), the behavioral effects of quinpirole were abolished. However, quinpirole-induced stereotyped responses were reinstated by SKF 38393 suggesting that D1 receptor stimulation by endogenous DA is necessary for D2 receptor-mediated stereotyped responses (sniffing, rearing). In support of this suggestion, stereotyped behaviors produced by the non-selective D1/D2 agonist apomorphine were not affected by AMPT pretreatment. In contrast to the effects of quinpirole, the ability of SKF 38393 to induce grooming responses was not abolished by AMPT pretreatment or by combined pretreatment with AMPT and reserpine (greater than 99% DA depletion). These results indicate that D1 receptor stimulation enables D2 receptor-mediated stereotyped responses, but that this relationship is not reciprocal since D2 receptor stimulation is not necessary for the grooming response elicited by SKF 38393. PMID- 2902645 TI - Attenuation of forgetting by pharmacological stimulation of aminergic neurotransmitter systems. AB - Mice were trained in one-way active avoidance to a criterion of 3/4 avoidances and tested under extinction conditions one week later when substantial forgetting had occurred. Thirty min prior to testing animals were injected with either saline or different doses of drugs which activate the noradrenergic (phenylephrine, salbutamol, clonidine) dopaminergic (L-dopa(Sinemet) transdihydrolisuride, apomorphine) and serotonergic (fluoxetine, 5-methoxy DMT) neurotransmitter systems. Results showed that all agents alleviated forgetting in a dose dependent fashion. Untrained mice treated with the most effective dose of representative drugs from each class did not exhibit avoidance behavior at testing indicating that the improved performance of trained animals was probably not the result of increased activity or other non-memorial effects of the drugs. It was concluded that pharmacological agents which stimulate monoamine systems may improve memory retrieval by activating a non-specific neural system which controls arousal, attention and motor readiness. PMID- 2902646 TI - Role of quisqualic acid receptors in the hypermotility response produced by the injection of AMPA into the nucleus accumbens. AB - alpha-Amino-3-hydroxy-5- methylisoxazole-4-propionate (AMPA) is an excitatory amino acid which on the basis of electrophysiological and binding studies appears to act as a quisqualic acid receptor agonist. AMPA and other excitatory amino acids, such as quisqualic acid, kainic acid, and N-methyl-D-aspartic acid, as well as picrotoxin, an inhibitor of endogenous GABA, produce a marked stimulation of locomotor activity after bilateral injection into the nucleus accumbens. The intraacumbens injection of gamma-D-glutamylaminomethylsulphonate (GAMS) was found to inhibit the hypermotility responses produced by AMPA and quisqualic acid at doses that were unable to inhibit the hypermotility responses produced by kainic acid, N-methyl-D-aspartic acid, and picrotoxin. These results suggest that GAMS is able to selectively inhibit quisqualic acid receptors in the nucleus accumbens. The intraacumbens injection of D-alpha-aminoadipic acid at a dose that significantly inhibited N-methyl-D-aspartic acid-stimulated locomotor activity did not produce a significant inhibition of AMPA-stimulated locomotor activity, suggesting that AMPA is not acting at N-methyl-D-aspartic acid receptors. Thus, these results suggest that the activation of quisqualic acid receptors in the nucleus accumbens produces a hypermotility response. PMID- 2902647 TI - Selective protection from the inhibition by EEDQ of D1 and D2 dopamine agonist induced rotational behavior in mice. AB - Mice with unilateral lesions of dopamine nigrostriatal neurons produced by injecting 6-hydroxydopamine into the striatum exhibited contralateral rotational behavior to the non-selective dopamine agonist apomorphine, the D1 dopamine agonist SKF 38393, and the D2 agonist quinpirole. The non-specific dopamine antagonist EEDQ blocked the circling responses to the three agonists. Pretreatment with specific, reversible dopamine antagonists before the EEDQ injection selectively prevented this blockade. Thus, if mice were pretreated with the D1 receptor antagonist SCH 23390 before EEDQ and the animals challenged with the D1 and D2 agonists 24 hours later, the rotational response to quinpirole was still inhibited, but the response to SKF 38393 was now evident. Similarly, in mice pretreated with the D2 receptor antagonist sulpiride before EEDQ and again challenged with the D1 and D2 agonists 24 hours later, the rotational response to SKF 38393 was still inhibited but the response to quinpirole was no longer inhibited. These results indicate that in vivo blockade of either D1 or D2 subpopulations of dopamine receptors may be achieved by selective protection with a reversible dopamine antagonist given prior to the administration of an irreversibly acting dopamine antagonist such as EEDQ. PMID- 2902649 TI - Effects of dynorphins on body temperature of rats. PMID- 2902648 TI - Stimulation of ingestive behaviors following injections of excitatory amino acid antagonists into the median raphe nucleus. AB - Anatomical and pharmacological evidence suggests that excitatory amino acids (EAA's) may function as neurotransmitters within the median raphe nucleus (MR). Previous studies have shown that injections of EAA antagonists into the MR result in marked hyperactivity. The current report extends these findings by demonstrating that intra-raphe injections of two EAA antagonists, kynurenic acid and 2-amino-5-phosphonovaleric acid, result in dose-dependent increases in food and water intake in nondeprived rats. These results suggest that EAA's within the MR may play a role in the control of appetitively motivated behaviors. PMID- 2902650 TI - Imidazole and yohimbine antagonize hypomotility, penile erection, stretching and yawning induced in rats by BHT 920, a selective dopamine autoreceptor agonist. AB - When the azepine derivative BHT 920, a putative agonist at dopamine autoreceptors, was injected i.p. into adult male rats at 100 micrograms/kg, it induced numerous penile erections, stretching and yawning and sedation, all considered typical signs of central DA autoreceptor stimulation, but did not elicit stereotyped behaviour. Imidazole (37.5-150 mg/kg i.p.) and the alpha 2 antagonist yohimbine (0.5-1 mg/kg i.p.) both antagonized the behavioural effects of BHT 920. In the light of the proposed selective action of the drugs used, the possible involvement of specific receptors for the modulation of these forms of behaviour, as well the possible relevance of the data presented, are briefly discussed. PMID- 2902651 TI - Decreased [3H]-naloxone binding and elevated dynorphin-A(1-8) content in Zucker rat brain. AB - We have previously reported that female obese Zucker rats are hypersensitive to painful stimuli and are resistant to the analgesic effects of morphine. In continuation we hypothesized that these phenomena are possibly the result of diminished population of opioid receptors, or an overabundance of dynorphin interfering with morphine analgesia. We now report that female obese Zucker rats have decreased concentrations of mu opioid receptors in whole brain and elevated levels of Dynorphin A(1-8) (DYN) in a brain area known to be associated with responses to nociceptive stimuli. PMID- 2902652 TI - Non-amphetaminic central stimulation by alkaloids from the ibogane an vobasine series. PMID- 2902653 TI - Platelet monoamine oxidase activity and tardive dyskinesia. AB - A few studies of chronic psychiatric inpatients have reported an inverse association between platelet monoamine oxidase (MAO) activity level and tardive dyskinesia (TD). In contrast to these earlier findings, we found no significant or consistent association between platelet MAO activity level and TD occurrence when we controlled for other TD predictors in a case-control study of 80 outpatients maintained on neuroleptic medications. We did find, however, that black subjects had significantly lower levels of MAO activity than did whites in an analysis controlling for age, sex, and neuroleptic dose. PMID- 2902654 TI - In vitro spontaneous motility of gastric smooth muscles of the sheep. AB - Whole strips of muscle wall cut parallel to their corresponding longitudinal, circular or internal oblique orientations in the reticulum, rumen, omasal body, abomasal body and antrum and to the muscularis mucosae of the omasal leaves were mounted along a vertical axis and their mechanical activities recorded isometrically. The strips were perfused with Tyrode-Ringer solution at 37 degrees C bubbled with 100% O2 or a mixture of 95% O2 + 5% CO2. Spontaneous activity was observed in muscle strips from all regions but not all muscle strips were spontaneously active: markedly greater spontaneous activity and a greater sensitivity to stimulatory agents occurred with 100% O2. Spontaneous activity was unaffected by the ganglionic blocking agent hexamethonium (10(-5) M) whereas atropine (10(-6) M) had no effect, or reduced and in some cases with rumen only, abolished activity. Acetylcholine (10(-6)-10(-7) M) caused contraction of all muscle except muscularis mucosae from omasal leaves. Electrical stimulation evoked responses which included atropine-sensitive contractions, relaxations and rebound contraction especially following atropine. The experiments showed that both major muscle layers of the reticulum, rumen, omasum and abomasum in mixed layer preparations exhibited spontaneous activity when removed from the influence of their cholinergic innervation and this included atropine-resistant diphasic contractions of the internal oblique muscle of the reticulum. The muscularis mucosae of the omasal leaves exhibited spontaneous contractile activity unaffected by cholinergic agonists and antagonists. PMID- 2902655 TI - Prediction of remission after antithyroid drug treatment in Graves' disease. AB - A prospective study was carried out to determine the factors which influence response to antithyroid drug treatment in Graves' disease and to assess their predictive value. Eleven variables were included in the assessment and were subjected to discriminant analysis, log rank test and "survival" analysis. The patients were observed for a considerable period (mean duration 51 months). Carbimazole (mean total dose 8 g) was given in combination with thyroxine for an average of eight months to 72 patients. Thirty-five patients relapsed and 37 remain in remission. Thyrotrophin binding inhibiting immunoglobulins (TBII) were detectable in 74 per cent of patients at diagnosis and thyroid stimulating antibodies detectable in 70 per cent. At the end of treatment thyrotrophin binding inhibiting immunoglobulins and thyroid stimulating antibodies were present in 36 and 27 per cent of patients respectively. Levels of thyrotrophin binding inhibiting immunoglobulins were significantly higher both before and after treatment in the group who relapsed, but were not of prognostic significance in an individual patient unless the value was extremely high (TBII index greater than 70). The presence of thyroid stimulating antibodies was of no value in predicting outcome. HLA typing confirmed the known association of Graves' disease with HLA B8 and HLA DR3 but neither of these antigens conferred and increased likelihood of relapse. The likelihood of relapse is shown to be directly related to the severity of the disease at the time of diagnosis, as measured by the serum total T3, and to the size of the thyroid gland; it is not affected by age, family history of thyroid disease or ophthalmopathy. The data indicate that antithyroid drug treatment can be expected to induce long-term remission in patients with mild disease (T3 less than 5 nmol/l) and small thyroids; carbimazole at this dose level is inappropriate for patients with severe disease (T3 greater than 9 nmol/) and large goitres. PMID- 2902656 TI - Nonpalpable testes in young boys: evaluation with MR imaging. AB - A prospective evaluation of magnetic resonance (MR) imaging for localization of a nonpalpable testis was performed in 24 boys aged 11 months to 6 years. Definitive surgical follow-up was obtained for 15 nonpalpable testes in 14 patients who form the basis of this study. MR imaging correctly indicated the unilateral absence of a testis in six of seven patients prospectively and all seven patients retrospectively. Surgically localized undescended testes were identified with MR imaging in five of eight cases prospectively and seven of eight cases retrospectively. Like scrotal testes, undescended testes were hypointense to fat on sequences with a short repetition time (TR) and echo time (TE) in all cases, and hyperintense or isointense to fat on long TR/TE sequences in all but two cases. Inguinal testes were located along the course of a linear low-signal intensity structure that extended to the scrotum, which may represent the remnant of the gubernaculum testis. A low-signal-intensity band through the testis, presumably the mediastinum testis, was seen in five of the undescended testes. Although MR imaging can often be used to localize a nonpalpable testis, currently MR is not sensitive enough to allow complete exclusion of the diagnosis of an undescended testis; thus failure to localize a testis with MR imaging should not defer laparoscopy or surgical exploration when indicated. PMID- 2902657 TI - Growth-inhibitory properties of vasoactive intestinal polypeptide. AB - It has recently been demonstrated that several neuropeptides can affect cell growth. The mammalian tachykinins substance P and neurokinin A, which are present in peripheral sensory neurons, stimulate growth of cultured connective tissue cells. Substance P-like immunoreactivity has been demonstrated in neuroblastoma cell lines. Neuroblastoma cells also produce other neuropeptides, among them vasoactive intestinal polypeptide (VIP). We report here that VIP is a potent inhibitor of serum-induced DNA synthesis in cultured smooth muscle cells (SMC), whereas no growth-inhibition was seen in SMC exposed to neurokinin A, calcitonin gene related peptide, neuropeptide Y, somatostatin, or cholecystokinin. The growth-inhibitory effect of VIP was closely related to its ability to induce formation of cyclic AMP. Our results raise the possibility that peptides released by neurons, endocrine cells, as well as by transformed cells, may not only function as mitogens but also as inhibitory modulators of cell growth. PMID- 2902658 TI - Effect of cimetidine, ranitidine and omeprazole on postprandial gastrin and somatostatin release in conscious dogs. AB - During a first series of experiments, the gastrin responses to a meal were measured and compared to the responses seen after administration of cimetidine (2.5 mg/kg/h) or omeprazole (2 mg/kg). During a second series of experiments the effects of cimetidine (2.5 mg/kg/h), ranitidine (0.5 mg/kg/h) and omeprazole (2 mg/kg) on post-prandial gastrin and somatostatin release were determined in experiments during which the intragastric pH was maintained close to 6.4. During a third series of experiments, the effects of cimetidine (2.5 mg/kg/h) and omeprazole (2 mg/kg) on basal gastrin and somatostatin release were estimated. Postprandial gastrin release was increased by cimetidine and by omeprazole. When acidification of the gastric content was prevented by intragastric titration, postprandial gastrin release was increased by about 100%. No further increase was observed when the animals were concomitantly treated with cimetidine, ranitidine or omeprazole. Intragastric titration did not alter postprandial somatostatin release. Concomitant administration of H2 blockers decreased the somatostatin response to the meal, while concomitant administration of omeprazole did not alter this release. No significant changes were observed in basal gastrin or somatostatin levels after administration of cimetidine or omeprazole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902659 TI - [Results of the combination treatment of cryptorchidism with human chorionic gonadotropin and human menopausal gonadotropin]. PMID- 2902661 TI - [Revascularization of the right coronary artery using the right mammary artery]. PMID- 2902660 TI - [Anesthesia in the Prader-Willi syndrome]. PMID- 2902662 TI - [Classification and treatment of angina pectoris. The Angina Pectoris Task Force]. PMID- 2902663 TI - [Silent myocardial ischemia (II). Diagnostic methods, prognostic significance and treatment]. PMID- 2902665 TI - [Esophagojejunal fistula. Treatment with intravenous somatostatin. Apropos of a case]. PMID- 2902664 TI - [Conservative treatment of high-loss intestinal fistulas occurring postoperatively]. PMID- 2902666 TI - [Effect of tolbutamide on the activity of transglutaminase]. AB - Five obese patients were studied during 7 days, 750 mg of tolbutamide, per os, was given. Blood samples were drawn at basal state and at 3, 5, 7 days during the treatment and 6 days after it. The values of transglutaminase activity (that in the basal state were similar to that in the controls) decreased significantly at the seventh day of treatment (72.3%). This decrease was transient and rapidly returned to the basal values when the drug was suspended. The results suggest that sulfonylureas exert in part their hypoglucemic effect by modificating the insulin receptor binding through the inhibition of transglutaminase activity. PMID- 2902667 TI - [Fatal asthma]. AB - Fatal asthma is rare but constitutes a serious public health problem on account of the raised prevalence of the disease. The incidence of fatal asthma is estimated at 3/100,000 people in France and the incidence of fatal asthma has not ceased to rise in the world despite therapeutic progress. The principal risk factors recognised are: 1. longstanding asthma, 2. unstable asthma, 3. acute severe asthma with a prior history, 4. insufficiently treated asthma or poorly compliant patient, 5. the absence of surveillance by peak flow measurements, etc. The socio-economic factors and above all the psychological factors play a role which is not negligible. A poor evaluation of the severity of the crisis by the asthmatic has been suggested as a factor, but it is possible that the rapidity of the progression of the crisis in fatal asthma may be responsible for the physical inability of the patient to react to the situation. There is no reason to incriminate beta-mimetic agents in fatal asthma. The prevention rests on an improvement in treatment, the education of the asthmatic and an improvement in medical teaching. However, only improvement in the speed of admission of emergency cases will effectively permit a reduction in the incidence of fatal asthma. The system of auto-admission of patients at risk should be reserved for co-operative patients but the systematic medicalization for urgent cases of asthma merits further development. A better definition of the asthmatic population at risk for fatal asthma is necessary. PMID- 2902668 TI - [Arterial hypertension and diabetes mellitus: physiopathological and therapeutic aspects]. PMID- 2902669 TI - Epidural opiates and nerve blocks. PMID- 2902670 TI - Optimal pharmacological control of chronic cancer pain. PMID- 2902671 TI - Early bronchodilating effect of a new oral beta-2-receptor agonist (broxaterol) in bronchial asthma. AB - In order to determine the bronchodilating activity and safety of two beta-2 receptor agonists, broxaterol and procaterol, compared with a placebo, 12 patients with reversible airway obstruction were tested in a double-blind cross over study. The drugs were administered orally and the dosage of broxaterol was 0.5 mg, that of procaterol 0.05 mg. Measurements of forced expiratory volume in 1 s (FEV1), heart rate and blood pressure were performed before and 30, 60, 120, 240, 360, and 480 min after each treatment. Both drugs produced bronchodilation but broxaterol was statistically 30 min faster in producing this effect than procaterol (p less than 0.05). Moreover this effect for both drugs persisted significantly for up to 480 min compared with the effect of the placebo (p less than 0.005). There were no significant side effects with either drug. Heart rate and blood pressure did not show any changes in clinical significance for broxaterol or procaterol. In our study, broxaterol showed a faster bronchodilating effect than procaterol, and tolerance was the same for both drugs. PMID- 2902672 TI - Cyclic GMP affecting the tracheal nonadrenergic noncholinergic inhibitory system. AB - An association between guanosine 3',5'-monophosphate (cyclic GMP) and the nonadrenergic noncholinergic inhibitory system (NANCIS) has been demonstrated in the isolated bovine tissue (Bowman and Drummond, 1984). In order to investigate this association in the guinea pig trachea, we used cyclic GMP derivatives, guanylate cyclase activators (N-methylhydroxylamine (NMH) and nitroglycerin (NG)] and inhibitors [oxyhemoglobin (HbO2) and methylene blue (MB)]. Under general anesthesia paralysis, the animals were ventilated and hourly injected with atropine (0.2 mg/kg) and propranolol (1 mg/kg). Cervical segment of the trachea was converted to a closed tracheal pouch and then filled with Kreb's solution augmented with atropine (1 microM) and propranolol (3.5 microM). A decrease in the pouch pressure (Pp) reflected NANCIS nerve transmural stimulation (TS)--or drug-induced relaxation. Pharmacological agents were applied intravenously. At 2 11 min after injection, NMH and NG decreased baseline Pp and reduced TS-induced relaxation. NMH, which is more potent than NG in activating particulate guanylate cyclase activity, potentiated the TS-induced relaxation at high frequencies, but NG did not. HBO2 inhibited the TS-induced relaxation at high but not at low frequencies. In contrast, MB inhibited the relaxation at low but not high frequencies. The results suggest that activation of particulate or membrane bound guanylate cyclase potentiates NANCIS-induced decrease in Pp. Therefore, there is a possible association between cyclic GMP and the NANCIS in the guinea pig trachea. PMID- 2902673 TI - Drug treatment of pain syndromes. PMID- 2902676 TI - Drug treatment of hyperkinetic movement disorders. PMID- 2902675 TI - Drug treatment of headache: changing concepts and treatment strategies. PMID- 2902674 TI - Pharmacology of behavioral syndromes in neurology. PMID- 2902677 TI - [Effect of subinhibitory concentrations of antibacterial agents on the adherence of fimbriated Escherichia coli to uroepithelial cells]. PMID- 2902678 TI - [Two cases of psychotic state following normal-dose benzodiazepine withdrawal]. AB - We report two cases of severe withdrawal symptoms after abrupt discontinuation of a long-term normal-dose benzodiazepines (BZD) administration. Case 1, a 61-year old man, suffered from delirium on the 7th day after abrupt discontinuation of nitrazepam, 10 mg/day. Case 2, a 49-year-old woman, suffered from auditory hallucination on the 4th day and visual cognitive disorder on the 5th day after abrupt discontinuation of nitrazepam, 5 mg/day, and triazolam, 0.5 mg/day. A withdrawal syndrome after discontinuation of normal-dose BZD is uncommon, and a psychotic withdrawal reaction is even more uncommon. We show how a continuous administration of BZD for a period of longer than 6 months and the presence of severe insomnia are risk factors predictive of a psychotic reaction. We also explain the predictive method used to determine the onset time of such a severe state. In the case of a psychotic state, we recommend intravenous diazepam injection. To prevent withdrawal reaction, we also recommend a gradual reduction after administration of normal-dose BZD. PMID- 2902679 TI - [Clinico-anatomical characteristics in postvaccinal encephalitis and encephalomyelitis]. PMID- 2902680 TI - [Sleep stages in man--physiological profile and variations induced by psychotropic drugs]. PMID- 2902681 TI - Zaltidine: an effective but hepatotoxic H2-receptor antagonist. AB - Zaltidine is a new H2-receptor antagonist. This study compares the safety and efficacy of zaltidine with those of placebo in the short-term treatment of duodenal ulcer. One hundred and thirty-five patients were randomly allocated to 4 weeks' treatment with either 150 mg zaltidine once daily or placebo. Fifty-nine were treated for a full 4 weeks with zaltidine before the trial was stopped. Healing rates after 4 weeks of zaltidine and placebo were 86% and 19%, respectively (p less than 0.001). Five patients in the zaltidine group had increased serum aminotransferase levels at the final (4-week) visit. The values normalized when treatment was stopped. Liver biopsy specimens provide strong evidence of drug-induced injury. Hepatic damage was associated with plasma levels of zaltidine in the upper half of the observed range. Zaltidine appears to be an effective treatment of duodenal ulcer. However, the incidence of hepatic damage (8%) seems higher than with commonly used H2-receptor antagonists. PMID- 2902682 TI - Somatostatin release by human gastric mucosa. Studies in peptic ulcer disease and pernicious anemia. AB - Somatostation has been postulated to have a paracrine modulating role in gastrin and gastric acid secretion. We applied the organ culture technique to examine somatostatin release by explants of human gastric mucosa taken from patients with active duodenal ulcer, from control subjects, and from patients with pernicious anemia. Somatostatin was found to be released at a constant rate by antral explants during 3 h of incubation. In active duodenal ulcer antral and fundic 2-h somatostatin release (18.7 +/- 2.6 pg/mg tissue (means + SE), n = 75; and 27 +/- 3 pg/mg tissue, n = 94, respectively) was significantly lower than release by control antral and fundic mucosa (83 +/- 17 pg/mg tissue, n = 39, and 72 +/- 16 pg/mg tissue, n = 42, respectively) (P less than 0.01). Somatostatin release by antral and fundic mucosa of patients with pernicious anemia was also significantly decreased (20 +/- 8 pg/mg tissue, n = 12, and 7.6 +/- 2 pg/mg tissue, n = 12, respectively) (P less than 0.05). These results imply possible impairments of the paracrine release of somatostatin in peptic ulcer disease and in pernicious anemia. PMID- 2902683 TI - Comparative haemodynamic effects of betaxolol and propranolol in patients with cirrhosis. AB - The acute effects of betaxolol (10 mg, intravenously), a new cardioselective beta blocker, and propranolol (15 mg, intravenously) on splanchnic and systemic circulations were studied in two matched groups of six patients with portal hypertension due to cirrhosis. Similar decreases in hepatic venous pressure gradient and azygous blood flow--an estimation of superior portosystemic shunts- were observed after both drugs, whereas hepatic blood flow was not modified. The decreases in heart rate and cardiac index were also similar after betaxolol and propranolol. Both drugs induced a significant decrease in the fraction of cardiac output flowing through superior portosystemic shunts. These findings confirm that the marked effect of beta-adrenoceptor blocking agents on splanchnic circulation results both from the reduction in cardiac output and from a vasoconstriction of the portal vein territory, and demonstrate that this vasoconstriction of the portal vein area does not necessitate a beta 2-blocking activity of the drug. The similar efficiency of the two agents in decreasing the hyperkinetic circulation suggests that betaxolol merits further long-term study in the pharmacologic treatment of portal hypertension. PMID- 2902684 TI - Primary biliary cirrhosis, temporal arteritis (giant cell arteritis) and polymyalgia rheumatica in a single patient. AB - Primary biliary cirrhosis (PBC), an autoimmune disorder, is well known to be in some cases associated with some other autoimmune disorders. We report a patient with PBC who presented giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) which are probably both autoimmune disorders. PMID- 2902685 TI - Hormonal control of behavior: amines and the biasing of behavioral output in lobsters. AB - Hormones and neurohormones act on the nervous system to produce important changes in behavior. Amine actions in the lobster nervous system and their possible relations to aggressive behavior in lobsters were studied in order to explore how such changes might come about. PMID- 2902686 TI - Molecular neurobiology--a conference sponsored by the NIMH. PMID- 2902688 TI - AIDS virus coat activates T cells. PMID- 2902687 TI - Pharmacological induction of use-dependent receptive field modifications in the visual cortex. AB - Lasting modifications of the receptive fields of neurons in the visual cortex can be induced by pairing visual stimuli with iontophoretic application of the neuromodulators acetylcholine and noradrenaline or the excitatory amino acids N methyl-D-aspartate (NMDA) and L-glutamate. The modifications are obtained in less than 1 hour and persist for more than 40 minutes. Thus, acetylcholine and norepinephrine have a permissive role in use-dependent neuronal plasticity. These results support the notion of a postsynaptic threshold for neuronal malleability that differs from that of sodium-dependent action potentials. PMID- 2902689 TI - In vivo administration of anti-CD3 prevents malignant progressor tumor growth. AB - Malignant progressor tumors are only weakly immunogenic and can evade host recognition and rejection. One approach to therapy involves activation of the host antitumor cellular effector mechanisms. Since monoclonal antibodies to CD3 (anti-CD3) can activate T cells in vitro, an attempt was made to determine if tumor immunity could be achieved by the administration of anti-CD3 in vivo. T lymphocytes from mice injected with anti-CD3 showed increased interleukin-2 receptor (IL-2R) expression, increased proliferation to recombinant IL-2 (rIL-2), and enhanced reactivity in both an allogeneic mixed lymphocyte reaction and a mixed lymphocyte tumor culture. Malignant tumor growth in treated mice was also examined. The anti-CD3 treatment prevented tumor outgrowth that would have killed untreated animals and also stimulated an in vivo response against a malignant progressor tumor providing lasting tumor immunity. PMID- 2902690 TI - Limited immunological recognition of critical malaria vaccine candidate antigens. AB - Current vaccine development strategies for malaria depend on widespread immunological responsiveness to candidate antigens such as the zygote surface antigens and the sporozoite coat protein, the circumsporozoite (CS) protein. Since immunological responsiveness is controlled mainly by genes mapping within the major histocompatibility complex (MHC), the humoral immune response to the zygote surface antigens and the cytotoxic T lymphocyte (CTL) response to the CS protein were examined in MHC-disparate congenic mouse strains. Only two of six strains responded to the 230-kilodalton zygote surface antigen and another two strains responded to the 48/45-kilodalton surface antigen. From two mouse strains, expressing between them five different class I MHC molecules, there was recognition of only a single CTL epitope from the CS protein, which was from a polymorphic segment of the molecule. The restricted CTL response to this protein parallels the restricted antibody response to this protein observed in humans and mice. These findings suggest that subunit malaria vaccines now being developed may be ineffective. PMID- 2902691 TI - [Surgico-andrologic study of a group of patients operated on for cryptorchism]. PMID- 2902692 TI - [Prenatal diagnosis of carriers of hemophilia B in a Cuban family using DNA analysis]. PMID- 2902693 TI - Applications of microsurgery in urology. AB - The applications of microsurgery in urology have increased in the decade since urologists first used such techniques. The primary uses for microsurgery in urology at first were vasovasostomy, vasoepididymostomy, and testicular autotransplantation. Penile revascularization has recently become another procedure for which microsurgery is used with increasing frequency. As more urologists learn the techniques, other urologic applications for microsurgery surely will develop. PMID- 2902694 TI - The undescended testis. Hormonal and surgical management. AB - Cryptorchidism is the most common disorder of sexual differentiation in males, with an incidence of 3.4 per cent in the term newborn, decreasing to 0.8 per cent at 1 year of age. The mechanisms of normal testicular descent are multifactorial and include an intact hypothalamic-pituitary-testicular axis, as well as a normal gubernaculum and epididymis. In boys with cryptorchidism, the testes demonstrate degenerative changes histologically as early as 1 to 2 years of age. Both testes may be affected, even with a unilateral undescended testis. The most important long-term complications of cryptorchidism include infertility and testicular cancer. The risk of malignancy is 10 to 40 times higher in men with cryptorchidism than in normal men and is highest in men who have had an intra abdominal testis and in certain intersex conditions. Orchiopexy does not appear to lessen this risk. In clinical trials in the United States, hormonal therapy with hCG or GnRH has not been effective in causing testicular descent; therefore, orchiopexy remains standard treatment. However, hCG is recommended if the clinician suspects that a testis is retractile. Orchiopexy should be performed between 12 and 18 months of age to prevent the degenerative changes that are demonstrable by 2 years. PMID- 2902696 TI - The progressive Zollinger-Ellison syndrome in multiple endocrine neoplasia. AB - The problem of hypergastrinemia in patients with the syndrome of multiple endocrine neoplasia (MEN type 1) has become increasingly controversial since the introduction of the antisecretory H2 antagonists for the treatment of the Zollinger-Ellison syndrome (ZES). One of the questions in the management of ZES is whether the malignant potential of the gastrinomas or the recurrent complications of ulcer will be the ultimate cause of death. Another problem is whether the association of MEN is a favorable or unfavorable factor to the prognosis of patients with ZES. Hypercalcemia contributes to excessive gastrin secretion, thereby casting doubt on the diagnosis of ZES in the presence of MEN. Patients with MEN are also more likely than patients with ZES not to have gastrinoma on an exploratory laparotomy. The existing controversy concerns the choices of therapy in instances of progressive ZES associated with MEN or when there is a failure to detect a primary gastrinoma when exploration is performed. To highlight the debate, the clinical courses of two patients, observed during two and three decades, respectively, are presented. These patients were receiving high doses of cimetidine; in addition, conventional surgical treatment for ulcer and repeated biopsies for gastrinoma were performed. After total gastrectomies (as life saving procedures), both patients are well. PMID- 2902695 TI - Reinfusion of secretions from high-output proximal stomas or fistulas. AB - Patients with proximal stomas or high fistulas and defunctionalized intestine who are receiving total parenteral nutrition (TPN) often develop hepatic enzyme abnormalities and hyperbilirubinemia. A technique was developed to collect intestinal secretions from proximal stoma and to reinfuse these secretions into the distal part of the intestine. This technique was applied in eight patients with a disrupted intestinal tract. A significant decrease (p less than 0.05) in elevated serum bilirubin, alkaline phosphatase and gamma-glutamyl transpeptidase levels was observed. Alanine aminotransferase and aspartate aminotransferase levels did not change significantly. The plasma sodium levels, slightly subnormal before reinfusion (131.0 +/- 4.6 millimolar per liter), despite enormous supplementation, normalized during reinfusion (137.0 +/- 4.0 millimolar per liter). TPN was continued during this infusion. This suggests that TPN by itself does not cause intrahepatic cholestasis. Neither could it be explained by an effect of secondary bile acids because these were most likely not produced as bile did not reach the distal defunctionalized intestine. Three possible mechanisms are suggested. Restoration of passage in the distal intestine may diminish bacterial overgrowth, endotoxin production and absorption. Enlargement of the bile acid pool may diminish the susceptibility of the liver to the deleterious effects of endotoxins. We advocate this reinfusion technique to overcome the metabolic disturbances occurring in those patients with high-output stomas or fistulas arising from the proximal parts of the small intestine. PMID- 2902697 TI - The septic foot in patients with diabetes. AB - Sixty-five lower-extremity amputations were performed as a result of sepsis in diabetic patients during a 3-year period. Chronic plantar ulcer was the most frequent cause of infection. Other causes of infection included ischemic gangrene, trauma, and web space fissures. Advanced ischemia was infrequent; only 21 (32.3%) had ankle-brachial indices (ABI) less than 0.5. Eight (23.5%) deaths and 12 (35.3%) stump failures followed 34 amputations where the stump was closed, compared with no deaths and 4 (12.9%) stump failures when open amputations were done (p less than 0.02). Partial foot amputations with aggressive local debridement resulted in healing in 10 (71.4%) of 14 cases with revision or grafting. Guillotine transmalleolar amputation is advised when foot salvage is not possible, because only 1 (5.9%) of 17 such procedures could not be revised to the below-knee (B-K) level, whereas 8 (33.3%) of 24 definitive, closed B-K amputations were unsuccessful (p less than 0.02). Infections were polymicrobial, with 5.8 bacterial isolates and 2.3 anaerobes recovered per patient. Anaerobic antibiotic coverage, however, failed to alter outcome. Sepsis, often without advanced ischemia, is an important cause of limb loss in patients with diabetes. Open amputations are recommended, with foot salvage possible in many cases. PMID- 2902698 TI - [Drug information. Pentasa--new Danish drug]. PMID- 2902699 TI - [Bone marrow transplantation in tumor diseases of the blood system]. PMID- 2902700 TI - Long-term health care in Texas: the time for serious study is now. PMID- 2902701 TI - New developments in the treatment of anxiety disorders. PMID- 2902702 TI - [Somatotropin: endocrinological aspects]. AB - Bovine somatotropin (BST) is a polypeptide hormone produced by the pituitary gland. Its release is regulated by hypothalamic hormones such as the Growth Hormone Releasing Factor (GRF) and the Somatotropin Release Inhibiting Factor (SRIF). Unlike somatotropin, GRF en SRIF are not species-specific. Somatotropin is released into the blood, and then bound to receptors which are present in various tissues but not in those of the mammary gland. Binding of somatotropin to receptors of hepatocytes results in the synthesis of somatomedins which are mediators of somatotropin. Receptors for somatomedins were recently found to be present in mammary gland tissue. The release of somatotropin is pulsatile and is influenced by steroids, genetic factors, nutrition and pregnancy. The effect of BST is dependent on its average concentration in the plasma and not on a particular pattern in this concentration. The effect of administration of BST prior to peak lactation is variable, but subsequently continuous to be positive. It therefore is advisable to start treatment after day 90. In the future, administration of recombinant-BST will be performed through slow-release preparations. PMID- 2902703 TI - The spectrum of GH responses to GHRH and somatostatin in patients with acromegaly. AB - Plasma GH responses to GHRH and somatostatin were examined in 43 patients with active acromegaly. Thirty-two of these patients showed GH increases 50% above the basal values in response to at least 1 of 3 stimuli (TRH, LHRH, arginine) (categorized as group I). The remaining 11 patients showed no response to any of the stimuli (categorized as group II). Following somatostatin infusion, group I (n = 31) showed significantly greater GH suppression than group II (n = 11) from 30 to 90 min (p less than 0.05-0.01). In addition, plasma GH responses to GHRH at 15 and 30 min was also greater in group I (n = 12) than in group II (n = 5) (p less than 0.05 & 0.01). There was a positive correlation between the log value of the peak GH after GHRH and the maximal % decrement after somatostatin (r = 0.64, p less than 0.02). However there were no differences in the responses of normal thyrotrophs (TSH) to TRH between the two groups. These results indicate that there are two types of acromegaly, i.e., one is more responsive and another is less responsive to either non-specific (TRH & LHRH) or specific GH stimulations (GHRH & somatostatin). PMID- 2902704 TI - Low susceptibility of trophozoites of virulent Entamoeba histolytica to cellular and antibody-dependent cellular cytotoxicity by guinea-pig effector cells. AB - Cytotoxic potentialities of lymphocytes and macrophages were determined against trophozoites of virulent and avirulent sublines of Entamoeba histolytica in vitro. Guinea-pigs were immunized with antigens of both sublines to obtain stimulated effector cells and antiamoebic antibodies. Trophozoites of an avirulent/attenuated subline of E. histolytica (NIH200) were significantly more susceptible to killing by lymphocytes and macrophages through cellular and antibody-dependent cellular cytotoxic mechanisms. The resistance of virulent trophozoites to killing was attributed to their higher phagocytic ability and virulence characteristics. Electron microscopic studies of the interactions showed that contact between the effector cells and the trophozoites was essential for the cytolytic event which resulted in disintegration of the trophozoites. Antigens of trophozoites of the virulence subline of E. histolytica (NIH200 V) were effective in inducing cytotoxicity against both virulent and avirulent trophozoites: however, the reverse was not true. PMID- 2902705 TI - The prevalence of Entamoeba histolytica in lactating women and in their infants in Bangladesh. AB - Entamoeba histolytica was studied in 33 lactating women and their infants in a periurban village in Bangladesh. Infant-mother pairs were followed for a period of 10-15 months: 67% of mothers excreted E. histolytica during the observation period, the majority for 3 months or more. Only one mother was symptomatic, with a mild, non-dysenteric diarrhoea. 58% of mothers were seropositive, several of them continuously and with a high titre, indicating past invasive infection. 67% had detectable antibodies in breast milk and 36% in saliva. Despite the high prevalence of E. histolytica in these mothers, infants were mostly uninfected: E. histolytica cysts in small numbers were found in only 2 of 1200 samples from infants aged 6 and 10 months. Several of the children were infected with Giardia lamblia. Although lower exposure to E. histolytica than to Giardia may account for the difference in infant infection rates with these parasites, defence mechanisms possibly exist which protect against E. histolytica but are ineffective against Giardia. PMID- 2902706 TI - Mixed hematopoietic chimerism following bone marrow transplantation. PMID- 2902707 TI - Prostasome membrane associated enzyme activities and semen parameters in men attending an infertility clinic. AB - Seminal plasma from 22 men attending an infertility clinic was subjected to preparative ultracentrifugation for 2 h at 105,000 g. The pelleted material as well as the supernatant thus obtained were investigated with regard to prostasome membrane-linked enzyme activities in relation to other semen parameters. The mean activity of Zn2+-dependent adenosine triphosphatase in the sedimented prostasome fraction was 1.45 +/- 1.02 mumol (range 0.29-4.79) orthophosphate released per milligram protein and 20 min, while the corresponding figures for the supernatant were 0.56 +/- 0.30 (range 0.12-1.29). Hence, 72% of the specific activity was sedimented, and 28% remained in the supernatant. The same pattern was recognized with regard to the other two enzymes investigated, although they displayed individual characteristics with regard to distribution after ultracentrifugation. The pelleted prostasome-linked mean aminopeptidase activity was 0.39 U/mg protein (81.9%), with only 0.087 U (18.1%) remaining in the supernatant. The corresponding figures for gamma-glutamyltransferase were 7.89 (60.4%) and 5.17 (39.6%) mu kat/g protein, respectively. The different enzyme activities in the prostasome fraction and supernatant, respectively, were interrelated to each other and correlated significantly with r values between 0.73 and 0.93 (p less than 0.001). It was concluded that a minor fraction of prostasomes remained in the supernatant after ultracentrifugation. A relationship existed between prostasomes and semen volume revealing a rather consistent pattern in that small volumes favoured the presence of comparatively more prostasomes in the supernatant and less prostasomes in the pelleted fraction than large volumes. In addition, the sperm concentration seemed to be another determinant of the distribution of prostasomes in seminal plasma on subsequent ultracentrifugation. PMID- 2902708 TI - [High-resolution sonography in cryptorchism]. AB - The importance of high-resolution sonography in the localization of undescended testes was displayed by an evaluation of 18 patients. In 15 patients the testis was not palpable on one side. In 3 cases, there was retention of the testis on both sides. Out of 17 testes in the inguinal region or in the external iliac region, 16 were located sonographically. There were 4 intraabdominal testes, and 2 were located sonographically. The retained and impalpable testes were in superficial positions in most cases. Hence, sonography proved to be the primary imaging method for localization. The importance of computed tomography, magnetic resonance imaging and phlebography of the internal spermatic vein are also discussed. PMID- 2902709 TI - A new fimbrial antigen on Escherichia coli strains isolated from zebu (Bos indicus) calves with diarrhoea in Brazil. PMID- 2902710 TI - Microsomal enzyme induction by permethrin in rats. AB - The synthetic pyrethroid, permethrin, was evaluated for its ability to alter hepatic microsomal drug-metabolizing function. The influence of permethrin (25:75 cis-trans) on plasma antipyrine kinetics and gamma-glutamyl transpeptidase (gamma GTP) activity were studied in rats. After 3 days of administration of 90 mg permethrin/kg/day, there was no significant change in the antipyrine half-life and the area under the curve, while the apparent volume of distribution and clearance were significantly increased. Treatment with 190 mg permethrin/kg/day for 3 days decreased antipyrine half-life and the area under the curve, and increased the apparent volume of distribution and the clearance significantly. The gamma-GTP activity was significantly increased within 21 days and 14 days after the start of permethrin administration, at doses of 90 and 190 mg permethrin/kg/day, respectively. The antipyrine kinetics results indicate that permethrin is capable of producing a dose-dependent marked enzyme-inducing effect. PMID- 2902712 TI - Angiography and polyarteritis nodosa. PMID- 2902711 TI - Brain cellular injury and recovery--horizons for improving medical therapies in stroke and trauma. AB - An edited summary of an Interdepartmental Conference arranged by the Department of Medicine of the UCLA School of Medicine, Los Angeles. The Director of Conferences is William M. Pardridge, MD, Professor of Medicine. After ischemic and traumatic brain injury, many cells may be rendered dysfunctional but are not irreversibly damaged or disrupted. The brain tissue may become metabolically deranged, and neurons, while still alive, are paralyzed and cannot create an action potential or conduct an electrical impulse. This injured brain tissue is in a precarious state of increased vulnerability. If the milieu of the favorable, they may recover; if it is slightly unfavorable, they may die. There is now evidence that reversibly injured brain tissue will die from an ischemic or hypoxic insult ordinarily tolerated by the normal brain. The major challenge of modern research in stroke and trauma is to define the chemical and metabolic milieu in which the injured brain exists and to define an ideal milieu for healing. PMID- 2902713 TI - [Development and significance of estrogen-induced increase in the activity of several liver enzymes]. AB - In experiments on adult, female rats, the author confirm the stimulatory effect of 50 micrograms kg-1 17-beta-estradiol daily, s.c., for more than 1 week on the activity of liver tyrosine aminotransferase and tryptophan pyrrolase and describe experiments suggesting an increased glucocorticoid sensitivity, as a consequence of the estrogen treatment. The study contributes to the information on potential side effects of hormonal contraception. PMID- 2902714 TI - [Endocrinology from the veterinary viewpoint]. AB - The neurohormonal research of our days succeeded in clearing up the psychic function of animals. The results of veterinary endocrine research gained importance also for the biological basis of human psychiatry. PMID- 2902716 TI - [Effect of benzodiazepines on the activity of a number of enzymes of purine metabolism in the brain tissue of rats]. PMID- 2902715 TI - [Affect from the biological and psychiatric viewpoint]. AB - The human frame of mind is a biological and psychic problem. The man is able to influence his mood in contrast to the animal, because the human brain is functionally an open system. The questions, which result from this opinion will be demonstrated. The influence of psychopharmaca and of drugs is an actual problem of human behaviour and must be considered in the therapy of mental disturbances. PMID- 2902717 TI - [Surgery of the endocrine pancreas]. AB - After classification of the endocrine tumours of the pancreas our group of patients during the last 17 years is demonstrated including patients with nesidioblastosis in every case except one with islet cell carcinoma. Beside typical anamnesis and symptoms, diagnosis was confirmed mainly by the glucose/insulin-ratio, the extremely low fasting blood glucose and the increased need of glucose supply for normalisation. Medical therapy with somatostatin and/or diazoxide was not successful in any case for a longer time, although in persistent cases nesidioblastosis became treatable postoperatively with diazoxide. Usually, a so-called 7/8-resection was performed. Typical complications from surgical management of pancreatectomy did not occur none of the children died. As for long-term results, no patient suffered from insulin dependency or insufficiency of the exocrine pancreas; reoperation was also never necessary. The established neurological damage of children who had been operated on late, could not be repaired. Despite the heterogeneous forms of the samples, histochemical investigation established nesidioblastosis in every pancreas specimen. An explanation of the histological findings would be a failure of the B cell-function as pathogenetic cause of nesidioblastosis. PMID- 2902718 TI - [Surgical protocol and intraoperative considerations in interventions on the testis]. AB - The surgical treatment of incompletely descended of the testes depends on the type of the undescended testis, the age of the patient, and the time of treatment. In a few years' time new techniques of autotransplantation may solve the problem of repositioning the testes in the scrotum. Exact knowledge of possible malformation of the testes and epididymis is essential for the paediatric surgeon. Torsion of one testicle with possible autoimmune impact involving the healthy testicle requires immediate exploratory surgery and treatment according to age. Paediatric carcinoma of the testes is rather rare, whereas treatment and prognosis vary with the histological type. Accurate classification and cooperation with a centre for paediatric oncology are essential. PMID- 2902719 TI - [Detection of fibria-like surface structures in Staphylococcus saprophyticus as a pathogen in chronic pyelonephritis]. AB - It is reported on a 25-year-old female patient suffering from chronic pyelonephritis. Six times coagulase-negative staphylococci were bacteriological proved in a significant number. Four strains were identified as Staphylococcus saprophyticus. The in each case in the autumn occurring complaints could be correlated well with the seasonal fluctuations of urinary tract infections by S. saprophyticus as described in the literature. Chemotherapeutic measures be determined by the clinical symptoms and subjective complaints of the patient. By an antibiotic therapy only a temporary loss of complaint and normalization of urinary findings, respectively, were obtained. In the presence of a marked leukocyturia a capsula-fashioned variant of S. saprophyticus was established. By scanning electron microscopy investigations fimbria-like surface structures were detected for the first time in this germ species. Three morphological different appendage structures are described. By a hypothetical model possible functions of these structures in the adherence process are discussed. PMID- 2902720 TI - The management of retained testis based on our investigations. AB - The follow-up examinations of 300 children operated for retained testis are reviewed. A total of 128 children (i.e. 42.6% of them) were operated up to the desirable 3 years of age, while 37 children, i.e. 12.3% of the patients, were over 13. The examinations recommended for judging objectively the pathological state, i.e. the condition of the testicles, are surveyed. (i) In operations performed over the age of 3 years, collection of samples for histological study to judge the condition of the testicular substance. (ii) Volumetry of the testis performed by an orchidometer of the authors' design, which provides comparative information for establishing the developmental conditions. (iii). During the diagnostic and control examinations, the simple, rapid, inexpensive and non invasive foil thermography was found useful which may furnish comparative data on the blood supply and the position and size of the testicles. The results of 322 operations, i.e. 95% of the patients, could be followed up and according to them, 286 operations (i.e. 89%) were revealed to be successful. The operative technique is also described. The role of retained testis in fertility is analysed. It is pointed out to be decisive in further improvement of the results that the children be operated as early as possible but at least up to their age of 3 years! This requires a certain change of attitude and a better organized paediatric urological care from the physicians in this field. PMID- 2902721 TI - Assessment of insulin action in man: role of hyperglycemia. AB - The effect of hyperglycemia on insulin-induced glucose metabolism (M) was investigated in healthy subjects using sequential clamp protocols at constant insulin + somatostatin infusions and varying plasma glucose. During euglycemia (4.8 mmol/l) M increased from 5.6 to 12.5 mg.kg-1.min-1 with increasing plasma insulin (0.34-3.00 nmol/l). At increasing glucose (6.7 mmol/l), M further increased (9.7 to 19.2 mg.kg-1.min-1) with the plasma insulin level (0.41 to 2.99 nmol/l). At a plasma glucose level of 9.8 mmol/l insulin (0.42 to 3.17 nmol/l) was still effective to increase M (13.7 to 25.2 mg.kg-1.min-1). Regression analysis showed that hyperglycemia does not only increase the maximal insulin stimulated M, but also decreases the insulin concentration causing a half maximum effect. During prolonged clamp studies M increased by about 10% per h, independent by the plasma glucose level. We conclude that hyperglycemia increases M by increasing insulin responsiveness as well as insulin sensitivity. Data derived from euglycemic clamp studies alone are of limited value with respect to the assessment of insulin action. PMID- 2902722 TI - Linkage of HLA-DR beta specific restriction fragment length polymorphisms with Graves' disease. AB - HLA-DR3 positive patients with Graves' disease (6 homozygotes, 7 heterozygotes, i.e. yielding 19 haplotypes) were studied by restriction fragment length polymorphism analysis using TaqI as restriction enzyme in order to look for polymorphisms in the HLA-DR3 allele of the human major histocompatibility complex. Polymorphic TaqI fragments of 11.6, 9.8 and 5.8 kb, each corresponding to HLA-DR beta sequences, were shown to differ in their prevalence in patients with Graves' disease and controls. The prevalence of DR3 polymorphisms in a total of 35 HLA-DR3-containing haplotypes was markedly different within patients with Graves' disease and Caucasian controls. Whereas a 11.6 kb fragment was rare in Graves' disease (2/19 haplotypes vs 8/16 in controls), the inverse ratio was found for a 9.8 kb fragment, with a prevalence of 17/19 and 8/16 haplotypes, respectively. A polymorphic fragment of 5.8 kb was exclusively seen in two DR3 containing haplotypes of patients with Graves' disease. Our data provide evidence that a DNA polymorphism of the HLA-DR beta genes, which is also reflected at the product level, is linked to Graves' disease. PMID- 2902723 TI - Sulfasalazine and new analogues in inflammatory bowel disease, with focus on Crohn's disease. PMID- 2902724 TI - [Myositis associated with ulcero-hemorrhagic rectocolitis. Apropos of a case]. PMID- 2902725 TI - [Endoscopic diagnosis of a cecal ameboma successfully treated with antibiotic therapy]. PMID- 2902726 TI - Management of severe heart failure. PMID- 2902727 TI - Pharmacological profile of neuromuscular blocking agents: present and future trends. PMID- 2902728 TI - Pharmacodynamics of neuromuscular blockade: a homogeneous phenomenon? PMID- 2902729 TI - Methods for postoperative acute pain management. PMID- 2902730 TI - Opioid drugs in chronic non-malignant pain? PMID- 2902731 TI - The spinal route of analgesia. PMID- 2902732 TI - Long term spinal opiate treatment. PMID- 2902733 TI - Morphological evidence for parallel processing of information in rat macula. AB - Study of montages, tracings and reconstructions prepared from a series of 570 consecutive ultrathin sections shows that rat maculas are morphologically organized for parallel processing of linear acceleratory information. Type II cells of one terminal field distribute information to neighboring terminals as well. The findings are examined in light of physiological data which indicate that macular receptor fields have a preferred directional vector, and are interpreted by analogy to a computer technology known as an information network. PMID- 2902734 TI - [Narcotic analgesics]. PMID- 2902735 TI - Pharmacological and contractile response of myocardium of Chagasic albino Swiss mice. AB - The isometric developed tension (IDT) and the pharmacological response of isolated myocardium from T. cruzi infected Albino Swiss mice in the acute and chronic Chagas' disease, were studied. The animals were infected with 7 X 10(4) trypomastigotes, form of T. cruzi, Tulahuen strain for the acute infection and with 45 parasites for the chronic stage. The isolated myocardium from acute and chronic chagasic mice reached IDT levels similar to normal hearts. The addition of norepinephrine (NE) to acute ventricles led to lower IDT values than in control group; this hyporeactivity to NE was absent in the chronic stage. On the other hand, epinephrine (EPI) effects on acute and chronic ventricles lead to significantly higher IDT values when compared with their controls. Propranolol blocked the higher effect of EPI in isolated myocardium from the acute stage, but the hyperreactivity described in the chronic stage could not be inhibited by the beta receptors antagonist. The agonist and antagonist tested act on cardiac plasma membrane beta receptors and their actions modify transmembrane calcium fluxes, so that the present study shows that Chagas' disease modifies the normal behavior of adrenergic beta cardiac receptors in different degree depending on the stage of the trypanosomiasis. PMID- 2902736 TI - Bethanechol-induced restricted stimulation of pancreatic juice secretion in mice. AB - Flow and enzymatic output from mouse pancreas were studied "in vivo" under bethanechol stimulation. A biphasic dose response curve was found in both, enzymatic output and juice flow, implicating that exocrine pancreatic juice secretion was also involved in restricted stimulation phenomenon. PMID- 2902737 TI - Cytostatic effect of neuroleptics. PMID- 2902738 TI - Prolactin suppressant effect of CQP 201-403, a new dopamine agonist, in hyperprolactinemic women. AB - To meet the need for a dopamine agonist compound which would offer longer action and improved tolerability, CQP 201-403 has been developed. CQP is a propyl ergoline which has shown specific and strong 24-hour prolactin suppression in healthy volunteers at oral doses from 0.01 mg and higher. In the study 24 hyperprolactinemic women were given once daily doses of 0.01 mg, 0.02 mg or 0.03 mg CQP 201-403, or placebo for 7 days in a double-blind study to assess the prolactin suppressant action and tolerability of the compound. The results show dose-dependent prolactin suppression following the initial CQP dose which was sustained in steady state, when a clear 24-hour action was seen. Tolerability was good and no drug attributable changes in safety measures occurred. On the basis of its facility to suppress prolactin at well tolerated once daily doses, CQP would offer an advantage over currently available drugs. Long-term therapeutic studies in hyperprolactinemia are therefore warranted. PMID- 2902739 TI - Sex steroids promote neurite growth in mesencephalic tyrosine hydroxylase immunoreactive neurons in vitro. AB - The influence of steroid hormones on the differentiation of catecholaminergic and serotonergic (5-HT) neurons was studied in dissociated cell cultures from embryonic day 14 (E14) rat diencephalon, mesencephalon and metencephalon treated for 6 days with 17 beta-estradiol (E), testosterone (T), 5 alpha dihydrostestosterone (DHT), progesterone (P), dexamethasone (DEX), or E + T. The effects of these hormones on morphologic differentiation were determined by morphometric measurements of total length of neurites of immunocytochemically identified neurons in culture, which were stained with antisera against tyrosine hydroxylase (TH) or 5-HT. A significant increase in neurite length was observed in cultures of TH-immunoreactive (TH-IR) neurons from the mesencephalon treated with E, T, E + T, but not with P, DHT or DEX. Based on labeling with [3H]dopamine (DA) uptake and competition with specific inhibitors, these mesencephalic TH-IR cells appear to represent DA neurons of the A8-A10 groups (which includes the substantia nigra). No statistically significant effects of these steroids were observed on TH-IR neurons from the diencephalon (assumed to be precursors of the tuberoinfundibular and incertohypothalamic dopaminergic groups). The 5-HT neurons of the raphe nuclei (metencephalon) showed no statistically significant response to steroids. We conclude that during the early fetal period, sex steroids can affect the morphologic differentiation of mesencephalic DA neurons in vitro, indicating that these hormones are capable of selectively influencing the development of a specific population of monoamine neurons during this critical period. PMID- 2902740 TI - Immunolocalization of dipeptidyl aminopeptidase (DAP IV) in the developing human brain. AB - By means of immunohistochemical techniques we have investigated the presence of dipeptidyl aminopeptidase IV immunoreactivity in brain material derived from human fetuses, newborns and aged persons. It was revealed that the enzyme protein is abundantly present in the immature human CNS. On the contrary the adult human brain contains much less dipeptidyl aminopeptidase immunoreactivity. It is speculated that the enzyme might play an important role in neuronal proliferation and/or differentiation especially with regard to its possible action on certain neuronotrophic peptides (IGF II, growth hormone). PMID- 2902742 TI - Modulation of GABA-stimulated chloride influx into membrane vesicles from rat cerebral cortex by benzodiazepines and nonbenzodiazepines. PMID- 2902741 TI - L-aspartate and L-glutamate binding sites in developing normal and 'nervous' mutant mouse cerebellum. AB - This study concerns the ontogeny and the cellular localization of L-aspartate and L-glutamate binding sites in normal and 'nervous' mutant mouse cerebellar membranes. The binding kinetics revealed for L-aspartate a single binding system (Kd = 750 nM) and for L-glutamate also a single binding component of higher affinity (Kd = 344 nM). The pharmacological study, using various amino acid analogues, revealed a differential specificity for the binding sites of the two amino acids. The developmental study showed that the binding sites of both amino acids appear mainly during the second and third week of life, a period when parallel and climbing fiber synaptogenesis occurs, but they follow a slightly different developmental pattern. The study using 'nervous', mutant mouse cerebellum showed an age-dependent decrease of L-aspartate and L-glutamate binding, which coincides in time with the Purkinje cell degeneration in this mutant, indicating a cellular localization of these binding sites on the Purkinje cell membranes. These results suggest that L-aspartate and L-glutamate binding sites may be respectively associated with the postsynaptic target of climbing and parallel fibers on the Purkinje cell dendrites. However, the decrease of specific binding in 'nervous' mutant mouse cerebellum was about 50% for L-aspartate and 60% for L-glutamate, implying that a significant number of L-aspartate and L glutamate binding sites are located on cerebellar elements other than the Purkinje cell membranes. PMID- 2902743 TI - Changes of 36Cl- flux and 35S-TBPS binding induced by stress and gabaergic drugs. PMID- 2902744 TI - Benzodiazepine, barbiturate, ethanol and hypnotic steroid hormone modulation of GABA-mediated chloride ion transport in rat brain synaptoneurosomes. PMID- 2902745 TI - Chronic benzodiazepine treatment increases the effects of inverse agonists. PMID- 2902746 TI - Non-uniformity of tolerance to the actions of benzodiazepine agonists. PMID- 2902747 TI - Pre- and post-synaptic aspects of GABA-mediated synaptic inhibition in cultured rat hippocampal neurons. PMID- 2902748 TI - Sialic acid and N-acetylgalactosamine specific bacterial lectins of enterotoxigenic Escherichia coli (ETEC). PMID- 2902749 TI - [Indications status and surgical treatment of spinal fractures. Attempt at a survey and determination of present status]. AB - Indications for operative treatment of spinal fractures sometimes are difficult to work out. Undoubtedly deteriorating neurological deficits require decompression always combined with stabilization. Due to new classifications a severe instability of the fracture, an axis deviation more than 25 degrees and polytraumatized patients show up being an indication for operative treatment. A proper preoperative planning with use of X-rays and CT Scan as well as the knowledge of the kind and site of instability is mandatory. In cervical spine fractures anterior fusion seems to be the best method. In thoracic spine fractures dorsally attached plates give enough stability. In the thoraco-lumbar spine region and in the lumbar spine itself the internal fixator with dorsal instrumentation together with a transpedicular bone graft is preferred by the authors. Among 384 fractures of the spine 62 have been operated. Both kinds of treatment do not compete; they are complementary instead. PMID- 2902750 TI - [Management strategy of multiple fractures of long tubular bones within the scope of polytrauma]. AB - Fractures of both femura in multitrauma patients have a high incidence of secondary respiratory failure. To avoid this vital complication as the first step to multiple organ failure femur fractures should be stabilised as soon as possible after successful treatment of hypovolaemic shock and acute life saving operations. The use of an external fixation in concomitant thoracic injury as a quick stabilisation, together with prophylactic mechanical ventilation, will probably lower the incidence of respiratory failure. PMID- 2902751 TI - [Injuries of the acromioclavicular joint]. AB - The injuries of the acromio-clavicular joint require a differentiated diagnosis and treatment. The classification of the acromio-clavicular dislocations from grade I to grade III according to Tossy is proved. The diagnosis of a complete acromio-clavicular dislocation (Tossy III) is an indication for a surgical repair. Many and different methods are reported in the literature. 178 patients with a fresh acromio-clavicular dislocation (Typ Tossy II and III) were treated at the BG-Unfallklinik Tubingen from 1970 to 1987 by suturing the ligaments, inserting pins across the joint and tension wire bending. In old cases with Tossy III dislocation of the acromio-clavicular joint an oblique osteotomy combined with the reduction of the clavicle is recommended as a method of choice. The results of these procedures and there possible intra- and postoperative complications are reported. The incision along the clavicle quite often gives scar problems. Therefore the advantages of an arched incision across the acromio clavicular joint is pointed out. Because of there biomechanical relationship fractures in the lateral third of the clavicle are similar to dislocations of the acromio-clavicular joint. The classification of these fractures according to Jager, Buschle and Breitner allows a differentiated management of these lesions. PMID- 2902752 TI - [Injury of the collateral ligaments of the metacarpophalangeal joint of the thumb and therapy]. AB - The authors report on their experience on 176 patients with lesions of the ulnar collateral ligaments. Two samples were compared: the fresh rupture and immediate suture, and the old lesion treated by a special plasty with palmaris tendon (Bauerle/Reill). The long term results (at least 2 years) of both collectives were nearly identical. The authors recommend immediate repair. PMID- 2902753 TI - [Current status of intramedullary nailing osteosynthesis]. AB - The article reviews the theoretical fundamentals and practical applications of intramedullary nailing. In particular, the author deals with the theoretical, mechanical and biological aspects, discusses the indications, and describes the definitely established results of medullary nailing. PMID- 2902754 TI - [Treatment of the open tibial fracture with the fixateur externe with special reference to osteosynthesis of the fibula]. AB - In the treatment of open fractures of the lower limb and of fractures combined with severe damage of soft tissues, external fixation is favoured. Additional soft tissue damages in the compartments of the lower limb are avoided by using an external fixation in form of a clamp. In defect fractures, shattered fractures and in all fractures in the distal third the stability of clamp fixation is enhanced by plating of the fibula. Furthermore by osteosynthesis the reconstruction of the correct length of the lower limb can be performed. 36 fractures healed definitively in an average of 17.1 weeks by this procedure. Secondary procedures were: 8 cases with decompression of compartments, 11 cancellous bone grafts, 13 fixateur externes were removed because of the infection of the Schanz'screws, and healing was achieved by using a plaster cast. The therapeutical procedure was changed in 5 patients to a plate osteosynthesis and in 8 patients to an intramedullary nail. PMID- 2902755 TI - [Lateral ligament injury of the anterior ankle joint in sports]. AB - During the last few years adequate therapy of ruptures of the fibular ligaments has been a subject of controversial discussions. Several authors consider operative and functional treatment to be almost equally good. In a retrospective study recent ankle ligament ruptures in 120 athletes were analysed with regard as to how the accident happened, the condition of the used sport shoe and the correlation between radiology and intraoperative findings. All cases were treated operatively because of an instability exceeding 10 degrees in the a.p.-stress X ray. In a follow-up examination including 80 patients 35 to 46 months after operative reconstruction subjective complaints, ability for sports as well as clinical and radiological findings were taken into consideration. Special attention was paid to the possibility of degenerative lesions after plaster immobilisation and to the results of x-ray stress stability examinations. The result of our study confirmed the superiority of operative reconstruction of a two-ligament-injury including a p.o. cast immobilisation. There were only a few cases with functional impairment or limitation of sports activities. No degenerative change could be detected via x-rays. In respect of literature studies, and based on our results, we recommend an individually adapted therapy concept depending on the special situation of the patient. Our follow-up treatment consists of early functional exercises in a windowed cast and a total immobilisation time with a walking plaster of 4 weeks. Alternative methods like the special shoe by Dr. Spring or functional splints are recommended for exceptional cases only. PMID- 2902756 TI - [Eosinophilic granuloma. Risk of fracture and rare site]. AB - The eosinophilic granuloma of bone, Letterer-Siwe's disease and Hand-Schuller Christian's disease are integrated under the conception Histiocytosis X. The same patho-histological findings, especially on bone and the observation that the 3 diseases can change one into the other are the reason for this conception. In the past the very different prognosis of the 3 diseases was the reason for difficulties of the classification and the therapy. In Letterer-Siwe's disease with bad prognosis and HSC with uncertain prognosis conservative therapy is mostly indicated. The eosinophilic granuloma in monotopic and polytopic localisation normally requires surgical procedure usually the excision of a specimen for the diagnosis. In special localisations with the fracture or the possibility of a fracture operative procedure with resection, bone grafting and osteosynthesis in order to get bone stability are indicated. 2 cases with special localisation are described. PMID- 2902757 TI - [Management and results of conservative treatment of patients with injuries of the thoracic and lumbar vertebrae]. AB - Conservative treatment of injuries of the thoracic and lumbar spine is indicated in stable fractures without or with an axis angle up to 25 degrees and in children fractures. Stable injuries are compression-wedge-fractures and burst fractures. Severe compression fractures with dorsal ligamentous injuries are regarded being conditional stable. Conservative treatment can be divided into 3 periods: lying period, rising period and stand-walk-sit period. Physiotherapy together with proper nursing is to avoid pulmonary and circulatory complications as well as to support motility of the intestinal tract. After stabilization of the general condition of the patient physiotherapy should furthermore lead to: relaxation of the hypertonic musculature, facilitating and preservation of muscle activities to secure the injured parts of the spine, training and assignment of global, diagonal muscle chains following physiological motions. From 1982-1986 389 patients with fractures of the spine were treated in the Tubingen Accident Hospital (Berufsgenossenschaftliche Unfallklinik Tubingen). An early functional treatment following Burkle de la Camp was performed in 84%. The follow up examination showed no further displacement in 84%. In 1/3 of the cases a free movement was regarded in the sagittal plane. 2/3 of the cases showed restriction of movement in only one segment. The good functional result is underlined by the subjective impression of the patient themselves: 2/3 were satisfied with the result. PMID- 2902758 TI - [Postoperative wound infection in trauma surgery]. AB - Our knowledge of the morphology and biochemistry of wound infection is still incomplete. Above all, the time and causal connections of the individual inflammatory phenomena are by no means satisfactorily clear. It is, however, an undeniable fact that the course of a wound infection depends most significantly on the time it was discovered. Transition between a beginning, impending, gradually creeping or overtly manifest wound infection is flowing and cannot be safely differentiated on the basis of the possibilities we have at our disposal today even in a hospital with fully update equipment. In our search for objectifiable early criteria of a wound infection we found that to date the determination of the lysozyme content in the wound secretion is a reliable and facile method. In fact, the composition and condition of the suctioned-off or drained-off wound secretion would deserve much closer attention in future postoperative wound control. If there is only the slightest suspicion of disturbance of physiological wound healing we should not show the slightest hesitation to make full use of the entire spectrum of therapeutic possibilities at our disposal to reduce the occurrence of septic wound complications to the barest minimum. PMID- 2902759 TI - [Antibiotic treatment in accident surgery. A status determination]. AB - Systemic antibiotic therapy in traumatology should be able to prevent contamination of the aseptic operation situs with pathogenic germs (as prophylaxis); or it should be able to reduce the bacterial flora in and around an infectious focus during and after operation. An adequate circulation in the bone and the soft tissue coverage is necessary for proper concentration of the antibiotics. --The commonly accepted indications for antibiotic treatment are listed and critically reviewed. Without a continuous germ control of the hospital flora no calculated antibiotic therapy is possible. PMID- 2902760 TI - Inhibition of cysteinyl-leukotriene production by azelastine and its biological significance. AB - Azelastine is a phthalazinone derivative with a wide spectrum of pharmacological activities. Actively sensitized guinea pigs were used to examine the broncholytic effect of azelastine in vivo. Furthermore, the influence of azelastine on the production of arachidonic acid (AA) metabolites was investigated in vitro and compared to the effects of nordihydroguaiaretic acid (NDGA), indomethacin and ketotifen. In vivo, azelastine protected actively sensitized guinea-pigs against ovalbumin-induced bronchospasm with an ID50 of 0.08 mg/kg orally. Ketotifen was similarly active (ID50 = 0.05 mg/kg). Antigen-induced contraction of isolated tracheal rings of sensitized guinea-pigs was concentration-dependently inhibited by azelastine and NDGA with IC50-values of 94.1 and 34.2 mumol/l, respectively. Ketotifen exerted only weak inhibitory activity (18% at 100 mumol/l). The arachidonic acid-induced contraction of isolated guinea-pig tracheal rings was also inhibited both by azelastine (IC50 = 92.6 mumol/l) and NDGA (IC50 = 20.4 mumol/l). Ketotifen was inactive on this model. Antigen challenge of chopped lung tissue from sensitized guinea-pigs resulted in the release of cysteinyl leukotrienes (LT) which were identified by reversed phase high pressure liquid chromatography (HPLC) as LTD4 and LTE4. The release of cysteinyl-LT from sensitized guinea-pig lung tissue induced by antigen challenge was concentration dependently inhibited by azelastine (IC50 = 35.2 mumol/l) and NDGA (IC50 = 8.4 mumol/l) but not by ketotifen and indomethacin. By contrast, indomethacin caused a pronounced augmentation of cysteinyl-LT release. The concentration of indomethacin, which augmented cysteinyl-LT release by 50% was 0.19 mumol/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902761 TI - The somatostatin/histaminic pathway balance on gastric secretion could be based on a competitive antagonism. AB - Measurements of acid and pepsin secretions and of histamine release in response to food alone or in combination with graded doses of antramine (AH), a molecular form of histamine isolated from antral mucosa, with or without somatostatin were performed simultaneously in dogs equipped with a denervated pouch. AH restored somatostatin-inhibited acid and pepsin secretions but with different intensities in regard to the different inhibitory levels induced by somatostatin. AH competitively antagonized somatostatin (1 microgram/kg/h) inhibition of acid secretion, but when stronger levels of inhibition were achieved, AH restored weakly acid secretion. Recovery of pepsin secretion occurred through a competitive mechanism between AH and somatostatin (1 and 2 micrograms/kg/h). There was a close relationship between the secretory outputs and the integrated histamine responses; the slopes of the regression lines might be considered as reflecting the stimulatory activity of blood histamine on secreting cells. For acid secretion, this activity is similar in control and somatostatin (1 microgram/kg/h) tests, while for pepsin secretion it is identical in control and 1 or 2 micrograms/kg/h somatostatin tests. One can speculate that the suppression of the somatostatin inhibitory effects by antramine, within the limits of physiological conditions, results from a competitive mechanism. PMID- 2902762 TI - Heterogeneity of histamine H2-receptor mediated responses in the rabbit aorta. AB - Distribution and properties of histamine H2-receptor mediated responses in segments of rabbit aorta was studied with histamine and H2-receptor stimulating drugs, dimaprit and impromidine. All agonists produced concentration-dependent tonus decreased in precontracted vascular strips, which were antagonised by selective H2-receptor antagonists, cimetidine and oxmetidine. Activities of the agonists were segment-dependent, and increased caudally along the aorta. A nonspecific smooth muscle relaxant, papaverine had homogeneous activity along the vessel, suggesting receptor specific nature of the observed heterogeneity. PMID- 2902763 TI - Xanthines--symptomatic or prophylactic in asthma? AB - Perhaps xanthines should not be classified as bronchodilators because their clinical efficacy may reflect their antiinflammatory properties more than smooth muscle relaxation. Xanthines inhibit late phase airway reactions induced by allergen or chemical sensitizers. But, they offer little protection against methacholine-, histamine, or allergen-induced immediate bronchoconstriction and any protection seen is unrelated to the extent of the initial bronchodilatation. The antiinflammatory effects of xanthines include stabilization of a variety of inflammatory cells that are present in asthmatic airways. Another potentially important effect is the increase in number, and activity, of "suppressor" T lymphocytes. Xanthines may also stabilize the barrier functions of both the airway epithelium and the airway microvessel (venular) wall. As a result less cellular and plasma-derived mediators are released, less plasma is exuded into the airway wall and less plasma enters the airway lumen. Penetration of inhaled macromolecules across the epithelium and into the airway wall may also be reduced. Future prospects for xanthines are interesting. A novel xanthine which lacks adenosine antagonist activity, enprofylline, has been shown to exert potent antiasthma actions without producing several of the excitatory, extrapulmonary, theophylline-like effects. We are only now starting to learn how xanthines actually work in the inflamed asthmatic and bronchitic airway. Nevertheless, the currently available data show that xanthines are likely to be more prophylactic than symptomatic in the treatment of asthma and chronic obstructive airway disease. PMID- 2902764 TI - An overview of the current status of the drug therapy of asthma. AB - The importance of inflammation as the central lesion in asthma is being increasingly recognised and it is proposed that the emphasis of therapy should be altered from simply treating symptoms, to trying to control inflammation at an early stage of the disease. A "tight control" treatment program to achieve this is outlined. Treatment regimes for asthma may therefore need to be re-assessed, although the most commonly used drugs (beta 2-adrenoceptor agonists, theophylline, corticosteroids and cromoglycate) are effective if used properly. For the majority of patients management is grossly inadequate in terms of diagnosis, assessment of disease severity and treatment. The death rate from asthma still remains unacceptably high and some strategies are outlined for the identification of patients at risk and the improvement of their management. This overview considers four central issues: (1) the lesions that should be the target for drug treatment; (2) an outline of the available drug treatment; (3) the aims of treatment and (4) the success of drug treatment in terms of morbidity and mortality. PMID- 2902765 TI - The drug therapy of asthma: directions for the 21st century. AB - There are several novel pharmacological approaches to asthma therapy which have resulted from a further understanding of airway smooth muscle function and inflammatory mechanisms involved in asthma. The most effective bronchodilators currently available are beta 2-adrenoceptor agonists and drugs with a prolonged duration of action after inhalation will be useful. Other possible bronchodilator approaches include vasoactive intestinal peptide, prostaglandins, novel xanthines, selective muscarinic antagonists, drugs interfering with intracellular calcium release and K+-channel activators. The most effective anti-inflammatory treatment is corticosteroids and efforts are being made to improve the topical potency of these drugs. Many other ways of reducing inflammatory effects in asthma are being explored, such as mediator antagonists (especially thromboxane and PAF antagonists), inhibitors of inflammatory cell activation (especially of eosinophils) and inhibition of neurogenic inflammation. Use of anti-inflammatory therapies earlier in the disease should become more widespread. PMID- 2902766 TI - New possibilities for the beta-adrenoceptor agonist bronchodilator drugs. AB - The pharmacological basis of the selectivity of bronchodilator beta-adrenoceptor agonists is discussed. Functional selectivity depends on both drug-related and tissue-related factors. Extensive enlargement of the beta-adrenoceptor agonist molecules permits interaction with hypothetical exoreceptor sites. A soft drug inhaled for local effects and which subsequently is inactivated by biotransformation, may give a minimum of systemic side effects. Conversely, a prodrug which requires metabolic activation offers new possibilities to alter the pharmacokinetic properties of a beta-adrenoceptor agonist. Several new compounds with interesting properties are presently subject to clinical trials. PMID- 2902768 TI - In vivo Junin virus-mouse macrophages interaction. AB - The role of mononuclear phagocytic cells in extraneural infection of the mouse with Junin virus (JV) was studied. Endpoint susceptibility (4 days of life) was evaluated by intraperitoneal (i.p.) inoculation of suckling mice. By means of immunofluorescence (IF) and C3 receptor assays, it was found that macrophages were permissive to viral replication in vivo and fostered the recruitment of inflammatory cells as evidenced by the absence of C3 marker. In support, in vitro infection failed to induce alterations of this receptor. Throughout, both in vivo and in vitro, there were no signs of C3-mediated phagocytosis. Silica treatment had no effect on either resistance or susceptibility, suggesting that the "macrophage-barrier" failed to hinder or favour the course of disease. Differences with other JV models are discussed. PMID- 2902767 TI - Different levels of hepatitis B virus replication among hepatitis Be antigen positive chronic carriers. AB - Detection of hepatitis B virus DNA polymerase (HBV DNA-pol) activity and of HBV DNA sequences in serum allowed to distinguish the different degrees of HBV replication in chronic HBsAg carriers. The amount of HBV DNA in the serum of 48 HBsAg and HBeAg positive patients in relation with the presence or absence of HBV DNA-pol was determined by dot-blot hybridization. The HBeAg positive cases with HBV DNA-pol activity had significantly higher HBV DNA levels than those which were DNA-pol negative (p less than 0.001). However, no significant differences with respect to liver function tests (transaminase, albumin, gammaglobulin) or to the histological diagnosis were found between both groups. Quantitative detection of serum HBV DNA in HBsAg chronic carriers may be helpful for learning the natural history of HBV infection and monitoring the antiviral therapy. PMID- 2902770 TI - Biological characterization of plaque-size variants of yellow fever virus in mosquitoes and mice. AB - We isolated plaque-size variants of a South American strain of yellow fever virus, and compared their ability to infect orally and be transmitted by vector Aedes aegypti mosquitoes with that of the uncloned, parental virus. We analyzed the same clonal isolates in mouse virulence experiments. No significant differences could be demonstrated in the capacities of the variants to infect and be transmitted by mosquitoes or in mouse virulence tests. The 17D vaccine virus (derived from the African Asibi strain) was, however, markedly attenuated in mosquitoes; also, a variant virus (Asibi strain) derived by continuous passage in HeLa cells (and attenuated for monkeys and mice) was markedly attenuated in mosquitoes when compared with its parent virus. The results suggest that vector competence and mouse virulence are similar in plaque-size variants of the South American strain of yellow fever virus. However, if vigorous and appropriate selection pressures are applied (as established by the derivation of the 17D vaccine and HeLa passaged viruses), attenuated variants can be discovered; their role and prevalence within a virus population in nature is unknown. PMID- 2902769 TI - Specific activity of tissue culture antirabic vaccine Rabivak-Vnukovo-32 with short intramuscular vaccination schedule. AB - Tissue culture rabies vaccine has been used for subcutaneous immunization of 158 subjects according to official instructions and also for intramuscular immunization of 128 subjects according to a short schedule with booster inoculations. All 286 subjects were either bitten or contaminated with saliva of rabid animals or animals suspected of having rabies. The 1168 serum samples were tested by neutralization test (NT) in mice, by radial haemolysis (RH) and by indirect haemagglutination (IHA). The highest, earliest and longest active post vaccination immunity was registered after the most intensive subcutaneous vaccination course at a dose of 5 ml for 25 days with 3 booster inoculations. Subcutaneous inoculation of 3 ml vaccine for 12 days (36 ml) failed to produce a satisfactory elevation of antibody titre. After 2 to 4 booster inoculations, however, a satisfactory level of antibody was observed. The tissue culture vaccine was shown to have good prospects for clinical vaccination by intramuscular route. On intramuscular vaccination at 1.5 ml for 9 days with 6 booster inoculations on days 16, 23, 30, 37, 67 and 97 (initial vaccine volume 45 ml) the mean geometric antibody titres (MGT) reached 93, 160, 322 and 165 on days 30, 60, 90 and 112, respectively. The economically efficient and rapid IHA and RH tests were confirmed to be specific and suitable for titration of antirabies antibody. PMID- 2902771 TI - Calculation of the frequency of congenital rubella syndrome in Poland. AB - The annual number and incidence of congenital rubella syndrome (CRS) in Poland was evaluated by means of a methematical model and on the basis of serological studies. In its principles this model describes the infectious kinetics of rubella by the formula y = 1--e-at, where "y" is the rate of immune persons, "a" is a parameter representing the transfer of susceptibles to immunes and "t" is age. The calculated incidence of congenital rubella syndrome resulted in average values of 0.15 to 0.38%, i.e. 15 to 38 CRS cases among 100,000 children born to mothers primarily infected by rubella virus during the first trimester of pregnancy. PMID- 2902772 TI - Varicella-zoster virus IgG antibodies during primoinfection in competent and transfer factor modulated immunocompromised host: comparison of three indirect assays. AB - Ten patients with acute leukaemia and next three with Hodgkin's or non-Hodgkin's lymphoma, suffering from varicella-zoster-virus (VZV) primoinfection, were given 1 to 2 doses of ultrafiltrate of the human leukocytes lysate (LLU) containing transfer factor (TF) activity (1 dose being equivalent to the product of 10(8) leukocytes). Only LLU administered to patients with acute lymphocytic leukaemia (ALL) at early phases of the illness (days 1 and 2) displayed a notable benefit on the clinical course of varicella. No influence upon the infection, on the other hand, was observed following LLU administration to subjects with lymphoma. The convalescent levels of IgG antibodies to VZV, as detected by indirect immunoperoxidase assay to membrane antigen (IPAMA), demonstrated no significant difference between infected competent and immunocompromised untreated and LLU treated individuals. The performance characteristics of IPAMA are compared with indirect immunofluorescence method (IFA) and non-competitive enzyme-linked immunosorbent assay (ELISA) on the same panel of specimens. PMID- 2902773 TI - Influence of detergents on measurement of influenza A virus haemagglutinin content in inactivated influenza vaccine by single radial immunodiffusion. AB - The influence of ionic, nonionic and amphoteric detergents or surfactants (SA) on determination of influenza A virus haemagglutinin content in the inactivated influenza vaccine by single-radial-immunodiffusion technique has been investigated. It was found that the action of different SA on IIV in SRID test is dependent on the mode of vaccine production, the procedure of virus inactivation and probably also on the specific structure of the antigen tested. Nevertheless, for nearly all SA used in this work the optimal concentrations (largest precipitation area) ranged from 1 to 2%; lower concentrations (except of amphoteric detergents) failed to yield an optimal effect. PMID- 2902774 TI - Seroepidemiology of haemorrhagic fever with renal syndrome in Bulgaria. AB - During the period of 1954-1986, 399 cases of haemorrhagic fever with renal syndrome (HFRS) were registered in Bulgaria with 63 (15.7%) deaths. Three hundred serum samples from 214 patients who had contracted the disease from 1957 to 1986 were investigated by indirect fluorescent antibody test (IF-AT). As antigen Vero E6 cells infected with the Asian Hantaan virus were used, as well as lung sections from bank voles (Clethrionomys glareolus) infected with strains Udmurt and Kazan 6-Cg from the European part of the U.S.S.R. Specific antibodies were detected in 194 sera, i.e. in 90.6% of persons investigated: in 131 single serum samples and in 63 paired sera. The results of the serological studies which covered 53.6% of all known local cases showed the territorial distribution of the natural foci in this country and the aetiologic relationship with the HFRS virus from the European part of the U.S.S.R. PMID- 2902775 TI - Neutralization kinetic analysis showed that strains of echovirus types 7, 11 and 17, unlike those of echovirus type 30, varied antigenically over time in Melbourne, Australia. AB - Using neutralization kinetic analysis, isolates of echovirus types 7, 11 and 17 were found to generally vary antigenically over periods of 22, 20 and 10 years respectively in Melbourne, Australia. This is in contrast to a previous finding of antigenic constancy amongst echovirus type 30 isolates in Melbourne over a 23 year period. PMID- 2902776 TI - A simple method of preparing a complement-fixing antigen from the virus of haemorrhagic fever with renal syndrome (Western type). AB - Different methods of the preparation of haemorrhagic fever with renal syndrome (HFRS) antigen for complement-fixation (CF) test are described. The antigens were prepared from the organs of suckling white rats inoculated with the Western type of HRFS by precipitation with polyethylene glycol, by fluorocarbon treatment and or by sucrose-acetone extraction. The highest CF titre was obtained by acetone precipitation of 20% brain suspension in isotonic sucrose. PMID- 2902777 TI - Detection of rinderpest antigen by latex agglutination test. AB - A slightly modified latex agglutination test was applied for detection of rinderpest antigen. The antigen was added to sensitized latex particles in the presence of hyperimmune antiserum to facilitate agglutination. Out of 129 samples tested by latex agglutination (LA), solid phase aggregation of coated erythrocytes (SPACE), reverse phase passive haemagglutination (RPHA) and counter immunoelectrophoresis (CIE) test, 86.0, 86.8, 84.4 and 79.8 per cent, respectively, were found positive. PMID- 2902778 TI - Classification of antiarrhythmic drugs. PMID- 2902780 TI - Benzodiazepines effective for treatment of anxiety and insomnia. PMID- 2902779 TI - The efficacy of the addition of nifedipine in patients with mixed angina compared to patients with classic exertional angina: a multicenter, randomized, double blind, placebo-controlled clinical trial. AB - Episodes of myocardial ischemia in patients with coronary artery disease may be due to transient increases in coronary vasomotor tone superimposed on a fixed atherosclerotic obstruction. The purpose of this study was to determine whether identification of the clinical pattern of angina could predict the therapeutic response to the addition of nifedipine to a regimen of beta blockers and/or long acting nitrates. Seventy-two patients with stable exertional angina were divided into two groups: "classic exertional angina" (17 patients), defined as exertional angina with a stable threshold; and "mixed angina" (55 patients), defined as exertional angina provoked by a variable threshold and/or at least two episodes of rest angina within the 3 months prior to screening. Patients were studied with nifedipine and placebo in a 6-week, double-blind, crossover design that used serial anginal diaries, exercise treadmill tests, and 24-hour ambulatory ECG monitoring. In patients with mixed angina, nifedipine reduced the frequency of angina compared to that during placebo treatment (13.1 vs 9.9 episodes/3 weeks, p less than 0.01) and reduced nitroglycerin consumption (11.7 vs 7.5 tablets/3 weeks, p less than 0.05); while in patients with classic exertional angina, nifedipine had no symptomatic effect (7.9 vs 6.8 anginal episodes/3 weeks, NS; 6.4 vs 5.8 nitroglycerin tablets/3 weeks, NS). Patients in both groups experienced a significant decrease in the manifestations of ischemia during exercise testing. Patients with mixed angina experienced a reduction in the daily frequency of painful episodes of ST segment depression during nifedipine treatment compared to placebo (0.6 vs 0.2 episodes, p less than 0.05), but there was no effect on the frequency of episodes of silent ischemia (4.2 vs 3.4 episodes, NS). In patients with classic exertional angina, the addition of nifedipine had no effect on any measure of ambulatory ischemia. We conclude that patients with mixed angina are more likely to benefit symptomatically from the addition of nifedipine therapy than patients with classic exertional angina. The lack of a consistently preferential response to nifedipine in patients with mixed angina, however, suggests that episodic coronary vasoconstriction may not be the only mechanism responsible for ischemia in these patients, and/or that nifedipine may not necessarily provide additional therapeutic benefit beyond that conferred by a regimen of beta blockers and/or nitrates. PMID- 2902781 TI - Sexual dysfunction in abusers of cocaine and alcohol. AB - Sexual dysfunction is not uncommon in alcoholics and in cocaine addicts. Alcohol abuse frequently develops along with cocaine dependence and the reverse is also common. We examined the sexual history of this common dually-addicted population. Sexual dysfunction was found in 62% (N = 50) of male cocaine and alcohol abusers consecutively admitted to a substance disorder treatment unit. The influence of cocaine and alcohol on commonly studied neurotransmitters and hormones along with their influence on sexual function are discussed. PMID- 2902782 TI - Abuse of benzodiazepines: the problems and the solutions. A report of a Committee of the Institute for Behavior and Health, Inc. AB - Benzodiazepines are medications used to treat many of the most frequent and disturbing symptoms seen in medical practice, including anxiety, insomnia, muscle spasms, some forms of epilepsy, and other illnesses. The World Health Organization (WHO) has determined benzodiazepines to be "essential drugs" that should be available in all countries for medical purposes. As benzodiazepines were recognized as generally safe and effective drugs, their medical use increased but so did problems of abuse outside medical practice. This report focuses specifically on the nonmedical use, or abuse, of benzodiazepines for purposes, durations, or at dosage levels not intended by the prescribing physician or in ways outside medical guidelines. The principal contribution of this report to the resolution of the controversy about the use of benzodiazepines is to draw a sharp distinction between the medical use of these drugs and their nonmedical use, which this report labels "abuse." Problems which exist with the medical use of benzodiazepines, such as their use by patients who are better treated with other medications (or without medication) and the problems of withdrawal symptoms on discontinuation of medically prescribed benzodiazepines, are not addressed because these are problems of routine, legitimate medical practice. On the other hand, aspects of medical practice which affect nonmedical use of benzodiazepines are extensively dealt with in this report including the diversion of legitimately prescribed benzodiazepines into the illicit drug market and the prescribing of benzodiazepines for drug abusers. Extensive animal and human research has shown that benzodiazepines are "reinforcing" drugs in the sense that animals and humans will maintain behavior on which delivery of the drug is dependent. Animal studies of self-administration of potentially abused drugs show that benzodiazepines are less powerful reinforcers than intermediate half-life barbiturates (such as secobarbital) and psychomotor stimulants (such as amphetamine and cocaine). A substantial body of human research has shown that benzodiazepines are moderately "liked" for their reinforcing effects by drug abusers and alcoholic subjects but that both anxious people and normal (non-drug abusing, non-anxious) human subjects prefer placebo to benzodiazepines, demonstrating that these substances are usually not liked by people who are not drug abusers or alcoholics. Among drug abusers, benzodiazepines are preferred less than either intermediate half-life barbiturates or stimulants. This difference between the response of substance abusers and normal and anxious research subjects supports the fundamental distinction PMID- 2902783 TI - The gene encoding the hydrophobic surfactant protein SP-C is located on 8p and identifies an EcoRI RFLP. AB - Pulmonary surfactant is composed primarily of phospholipids but also contains three known surfactant-specific proteins. These proteins are important in determining the physical properties of pulmonary surfactant--including its ability to adsorb to an air-liquid interface and its structure--but also appear to influence surfactant metabolism. We have previously assigned two surfactant proteins, SP-A (a 28-36-kDa glycoprotein) and SP-B (an 18-kDa hydrophobic protein), to the short arm of chromosome 10 and to chromosome 2, respectively. We now report that the gene encoding the 5-8 kDa hydrophobic surfactant protein SP-C is located on the short arm of chromosome 8. A cDNA clone encoding the entire protein recognizes a useful EcoRI restriction-site-length polymorphism. Evaluation of congenital syndromes manifesting autosomal abnormalities does not further elucidate the functional role of this protein in promoting normal respiratory physiology. PMID- 2902784 TI - Regional localization of chromosome 3-specific DNA fragments by using a hybrid cell deletion mapping panel. AB - A series of human chromosome 3-specific DNA fragments isolated and characterized from a lamda phage genomic library were regionally localized on human chromosome 3. This was accomplished using filter hybridization blot analysis of a human chromosome 3 hybrid cell deletion mapping panel. Twenty-three new anonymous DNA fragments were assigned to one of four physical regions of chromosome 3. Seventeen DNA fragments were mapped to the long arm of chromosome 3, including one DNA fragment that demonstrated a restriction fragment length polymorphism (RFLP). Five DNA fragments were assigned to 3p14.2----pter, including one highly polymorphic fragment sublocalized at 3p25----pter by in situ hybridization. This DNA fragment is the second reported distal 3p polymorphic probe. One DNA fragment was localized to 3p14----p14.2. In addition, three fragments previously assigned to chromosome 3 were confirmed. Polymorphic DNA probes DNF15S2 (formerly D1S1) and D3S2 were mapped to 3p14.2----pter. The previous 3p25 in situ localization of the c-raf-1 oncogene was supported by deletion panel mapping. The physical localization of these twenty-three new DNA fragments has more than doubled the number of cloned DNA fragments assigned to chromosome 3. These and future regional assignments of DNA fragment probes will facilitate construction of both a physical and genetic linkage map of chromosome 3. They may also be useful in characterizing the chromosomal and molecular aberrations involved in small-cell lung cancer (SCLC), renal cell carcinoma, other malignancies, and the 3p14.2 common fragile site. PMID- 2902785 TI - A genetic linkage map of 27 loci from PND to FY on the short arm of human chromosome I. AB - A genetic linkage map of 27 loci on the short arm of human chromosome 1 has been developed by analysis of the 40 families in the Centre d'Etude du Polymorphisme Humain (CEPH) reference panel. Probes that recognize 14 novel RFLPs at loci designated D1S9-D1S22 were isolated from a flow-sorted chromosome 1 library. A linkage map of chromosome 1p was constructed from the genotypic data at these 14 loci, RFLPs at eight cloned genes (PND, ALPL, FUCA1, SRC2, MYCL, GLUT, TSHB, and NGFB), two previously identified RFLPs (D1S2 and D1S57), two blood group antigens (RH and FY), and the isozyme PGM1. All 27 loci form a continuous linkage group, from FY to PND, of 102 cM in males and 230 cM in females. This map provides a basis for highly informative multipoint mapping studies for most of the short arm of chromosome 1. PMID- 2902786 TI - Recombinations between IRP and cystic fibrosis. AB - A candidate gene for cystic fibrosis was recently isolated by selective cloning of HpaII-tiny-fragment islands; it maps considerably closer to CF than does MET or D7S8 (pJ3.11), and DNA polymorphisms from this region are in marked disequilibrium with CF. cDNA cloning has shown that this protein has a growth factor-like structure and shows homology to the murine and human proto-oncogene int-1; it is designated IRP (int-1-related protein). DNA sequences from the IRP locus that recognize RFLPs are proving to be highly informative for prenatal diagnosis. We report five crossovers that have been identified which occur either within the IRP locus or between IRP and CF; these recombinants demonstrate that CF maps between the DNA markers D7S8 and KM.19. PMID- 2902788 TI - Linkage disequilibrium in the human insulin/insulin-like growth factor II region of human chromosome II. AB - Caucasian (N = 128) and Chinese (N = 84) subjects were typed for RFLPs in the insulin (INS)/insulin-like growth factor II (IGF2) region of chromosome 11. Both the analysis of extended haplotypes and the pairwise measures of linkage disequilibrium among the RFLPs indicate that there is extensive linkage disequilibrium in the INS/IGF2 region. The disequilibrium extends across the hypervariable region (HVR) located just 5' to the INS gene and encompasses a region of at least 40 kbp. Previous studies had suggested that linkage disequilibrium in the INS region was negligible and that this region may therefore contain a "recombinational hotspot" (Chakravarti et al. 1986). However, results of this and another recent study (Thompson et al. 1988) highlight the importance of the frequencies of associated alleles in the ability to detect linkage disequilibrium. Thus, the previous failure to detect disequilibrium in the INS region may have reflected a lack of power, rather than a true absence of disequilibrium in this region. PMID- 2902787 TI - Localization of the gene for X-linked recessive type of retinitis pigmentosa (XLRP) to Xp21 by linkage analysis. AB - The X-linked recessive type of retinitis pigmentosa (XLRP) causes progressive night blindness, visual field constriction, and eventual blindness in affected males by the third or fourth decade of life. The biochemical basis of the disease is unknown, and prenatal diagnosis and definitive carrier diagnosis remain elusive. Heterogeneity in XLRP has been suggested by linkage studies of families affected with XLRP and by phenotypic differences observed in female carriers. Localization of XLRP near Xp11.3 has been suggested by close linkage to an RFLP at the locus DXS7 (Xp11.3) detected by probe L1.28. In other studies a locus for XLRP with metallic sheen has been linked to the ornithine transcarbamylase (OTC) locus mapping to the Xp21 region. In this study, by linkage analysis using seven RFLP markers between Xp21 and Xcen, we examined four families with multiple affected individuals. Close linkage was found between XLRP and polymorphic sites OTC (theta = .06 with lod 5.69), DXS84 (theta = .05 with lod 4.08), and DXS206 (theta = .06 with lod 2.56), defined by probes OTC, 754, and XJ, respectively. The close linkage of OTC, 754, and XJ to XLRP localizes the XLRP locus to the Xp21 region. Data from recombinations in three of four families place the locus above L1.28 and below the Duchenne muscular dystrophy (DMD) gene, consistent with an Xp21 localization. In one family, however, one affected male revealed a crossover between XLRP and all DNA markers, except for the more distal DXS28 (C7), while his brother is recombined for this marker (C7) and not other, more proximal markers. This suggests that in this family the XLRP mutation maps near DXS28 and above the DMD locus. PMID- 2902789 TI - Molecular and cytogenetic characterization of a de novo t(5p;21q) in a patient previously diagnosed as monosomy 21. AB - Genomic single-copy DNA fragments were used to characterize an undetected chromosome translocation in an individual whose metaphase chromosome analysis revealed apparent monosomy 21. Eight RFLPs detected by six probes were used to identify homologous sequences from chromosome 21 in DNA digests from the proband and her parents. These family studies showed that the proband was disomic for the distal region of 21q. Reverse banding and in situ hybridization of chromosome 21 specific probes to metaphase chromosomes from the proband revealed a de novo translocation with breakpoints at 5p13 or 14 and 21q11 or 21. In situ hybridization permitted orientation of the translocated portion of chromosome 21 on the derivative chromosome 5 and, in conjunction with molecular analysis and previous mapping studies, refined the physical map for the long arm of chromosome 21. PMID- 2902790 TI - Alpha-globin gene cluster haplotypes in the Kalahari San and southern African Bantu-speaking blacks. AB - Alpha-globin gene cluster haplotypes were determined in Southern African San and negroid populations. Significant differences (P less than .01) between the two groups were found at three of the nine loci in the cluster. The most striking difference, however, was the relatively low level of variation found in the San (alpha alpha)-associated haplotypes and the high level in the SA blacks. This trend was also observed for the 3' hyper-variable region. Nineteen different haplotypes were identified among the 36 haplotypes studied in the black population, but only seven different ones were found among the 37 haplotypes in the San; five were common to both populations. The common San haplotype, (+--MPZ+ --), had a frequency of .57 in the San and .11 in the black population; the common SA black haplotype, (---MZ----), occurred at a frequency of .17 but was absent in the San. In the SA black population significant linkage disequilibrium is present between five of the RFLP loci, including the extreme 5' and 3' markers, confirming the absence of a recombination hot spot in the alpha-globin gene cluster. PMID- 2902791 TI - Genetic studies on the Senegal population. I. Mitochondrial DNA polymorphisms. AB - The mtDNA of 186 Senegalese, mainly Wolof and Peuls, were analyzed by means of six restriction enzymes: HpaI, BamHI, HaeII, MspI, AvaII, and HincII. Two of the HpaI, one of the HaeII, two of the MspI, and one of the AvaII morphs had not been described before. The only enzymes which enabled Wolof and Peuls to be differentiated were HincII and, to a lesser extent, HaeII. Important differences emerge in the comparison of Senegalese with Bantu of South Africa and with Bushmen, the only other Africans who, as far as we know, were studied for the same genetic markers. Though Senegalese mtDNAs display typical African features (presence and frequency of HpaI morph 3 and high incidence of AvaII morph 3), the distribution of MspI and AvaII patterns markedly differentiates Senegalese from the others. The phylogeny of mtDNA types in Africa well portrays how the three African groups are clearly distinguishable genetic entities. Bushmen lie at one end of the range of variability, Senegalese being at the other end but still fairly closely related to Bantu. The information provided by individual restriction enzymes to the distinction among the three major ethnic groups is reviewed and discussed. PMID- 2902792 TI - Efficacy of nifedipine gastrointestinal therapeutic system in combination with beta blockers in the management of exertional angina. A multicenter study of 54 patients. AB - This multicenter study assessed the efficacy of a new formulation of nifedipine in 54 patients with stable angina pectoris receiving beta-blocker therapy. This once-daily preparation of nifedipine was administered in double-blind fashion in doses of 30, 60, and 90 mg. All patients experienced pain-limited exercise at placebo baseline treadmill testing. Eight hours post-dose exercise testing resulted in a significant increase in time to onset of angina for all three dose levels of nifedipine but not for placebo. Exercise testing 24 hours after dosing showed significant improvement in time to angina and total exercise time for patients receiving 60-mg and 90-mg doses but not for the 30-mg or placebo categories. These preliminary results suggest that this new formulation of nifedipine is beneficial when added to stable doses of a beta blocker in patients in whom angina is still exhibited during exercise testing. PMID- 2902793 TI - Retinoids as generalized regulators of cellular growth and differentiation. PMID- 2902794 TI - Experience with multiple approaches to the prenatal diagnosis of the fragile X syndrome: amniotic fluid, chorionic villi, fetal blood and molecular methods. AB - We have had experience with 160 prenatal diagnosis cases for the fragile X syndrome [fra(X)] or Martin-Bell Syndrome. In 140, amniotic fluid was utilized; 98 had a documented family history of fra(X). The 94 completed cases included 4 no growth; 56 males of which 7 were fra(X)-positive and 2 false-negative; 38 females of which 5 were fra(X) positive. There was no fra(X) positive result when a family history of mental retardation was not documented as fra(X). Molecular methods (RFLPs) were utilized in 10 amniotic fluid and 5 chorionic villus specimens (CVS). Percutaneous umbilical blood sampling was used in 2 negative cases and 1 fra(X) positive case because of timing, tissue culture failure or confirmation of another method. CVS were received in 13 cases, and RFLPs were utilized in 5 of the CVS cases. There was no positive fra(X) CVS chromosome result in males, 1 positive result in a female, but 2 false negatives were detected by RFLPs. On the basis of the results, it can be concluded that cytogenetic and molecular methods are complementary and best used together and that multiple approaches can enhance the efficiency and reliability of fra(X) prenatal diagnosis. PMID- 2902795 TI - Improved DNA markers for efficient analysis of fragile X families. AB - We report the characteristics of two new probes that detect BclI RFLPs useful for analysis of fragile X families. With these two probes and a single blot, 34% of women are heterozygous both for the proximal marker DXS105 (closer to the fragile X locus than the factor IX gene) and for the distal markers DXS52 or the factor VIII gene. Combined with the analysis of previously described polymorphic markers, it is possible to have a majority of families fully informative for flanking markers using a limited number of probes and restriction digests. PMID- 2902796 TI - Multipoint linkage of 9 anonymous probes to HPRT, factor 9, and fragile X. AB - We have analyzed the segregation of restriction fragment length polymorphisms (RFLPs) associated with 9 anonymous probes detecting loci DXS10, DXS15, DXS19, DXS37, DXS51, DXS52, DXS98, DXS99, and DXS100 and probes for HPRT and F9 in a set of 40 families segregating fragile X (fra(X]. Using two-point and multipoint analysis, we have established their relative genetic locations. The results indicate that DXS99 and DXS10, unlike previous reports, are not tightly linked to F9. A new locus was found to map within the F9 - fra(X) region. DXS98 showed 6% recombination with fra(X) and appeared to be the closest locus to fra(X). These results will be useful for mapping the relative position of newly defined X probes in this region and for future genetic studies of families with fra(X), hemophilia B, or Lesch-Nyhan mutations. PMID- 2902797 TI - Linkage between the fragile X and F9, DXS52 (St14), DXS98 (4D-8) and DXS105 (cX55.7). AB - Linkage data using the markers F9, DXS105 (cX55.7), DXS98 (4D-8) and DXS52 (St14) are presented from 22 kindreds segregating with the fragile X. Two-point linkage analysis was carried out taking into account cytogenetic results and penetrance classes defined by mental impairment status of mothers. Recombination frequencies (theta) corresponding to the maximum z scores (z) were obtained between F9 (z = 3.48, theta = 0.18), DXS105 (z = 5.06, theta = 0.07), DXS98 (z = 4.79, theta = 0.01) and DXS52 (z = 6.44, theta = 0.09) and the fragile X. Recombination frequencies between marker loci in fragile X families are also presented. These recombination frequencies need to be combined with those from other studies in order to determine the best estimates of map distances for use in genetic counselling, until markers closer to the fragile X, or at the fragile X, can be used. Most potential fra(X) heterozygotes were informative for flanking markers using the above 4 probes. Carrier risks were determined by 3-point analysis using informative flanking markers, taking into account cytogenetic results. Low level fra(X) expression occurred in 2 probable non-carriers; emphasising the need for extreme caution in the interpretation of low rates of expression. PMID- 2902798 TI - Pulsed-field gradient-gel studies around the fragile site. AB - Using pulsed-field gradient-gel electrophoresis (PFGE) we compared two fragile X (fra(X] chromosomes from individuals in families that exhibit linkage heterogeneity between fra(X) and coagulation factor IX (F9). The analysis of very large restriction fragments indicated that there is a structural difference in the interval between fra(X) and F9 near the locus DXS105. Differences were observed in the Sfi I partial digestion analysis and in the Mlu I pattern of the DXS105 region. Digestion with Nru I and Sst II also showed differences between these alleles. The analyses suggest that the alleles differ in a region of greater than 200 kb. Analysis of other normal and fra(X) chromosomes will be necessary to determine whether the observed difference is a normal population variant or if it may be responsible for the linkage heterogeneity observed between these loci. PMID- 2902799 TI - Cytogenetic and physical mapping in the region of the X chromosome surrounding the fragile site. AB - Seven DNA probes have been mapped within the Xq27-Xq28 region using in situ hybridization, in some cases on chromosomes expressing the fragile site to enhance the resolution. To complement these studies and investigate the relationship between genetic, cytogenetic and physical distance some of these probes were used for large scale mapping using pulsed field gels. Physical linkage was demonstrated between two loci, F9 and MCF2, which are separated by less than 270 kb, and a restriction map extending over 1,300 kb has been generated. PMID- 2902800 TI - The antipsychotics. PMID- 2902801 TI - Effect of prolactin on enzymes of lipid biosynthesis in mammary gland explants. AB - Prolactin (PRL) stimulates an increased rate of incorporation of [14C]acetate and [3H]glucose into lipids in cultured mammary gland explants from 10- to 14-day pregnant mice. This response is biphasic with an early increase occurring from 6 through 12 h, and an additional increase from 16 through 24 h. Enzymes likely to be rate limiting to this process include acetyl CoA carboxylase, fatty acid synthetase, acetyl CoA synthetase, and/or pyruvate dehydrogenase. Of these enzymes only pyruvate dehydrogenase activity was elevated at 6 h, suggesting that this enzymatic activity is important in stimulating early increases in lipogenesis after PRL treatment. In addition, the PRL stimulation of pyruvate dehydrogenase may also indirectly stimulate acetyl CoA carboxylase through the generation of citrate; this may explain the early (6-12 h) effect of PRL on [14C]acetate incorporation. After 16 h of PRL treatment, the activities of all the lipogenic enzymes were enhanced. The second phase of PRLs stimulation of lipogenesis thus likely involves the enhanced activities of more than one of the lipogenic enzymes. PMID- 2902802 TI - Pertussis toxin-sensitive cholinergic inhibition of somatostatin release from canine D-cells. AB - Development of an enriched cultured cell system allowed us to investigate the mechanism of cholinergic inhibition of somatostatin release stimulated by adenosine 3',5'-cyclic monophosphate (cAMP) and Ca2+-protein kinase C-dependent pathways of cell activation. After a 24-h culture on rat tail collagen, D-cells, quantified by immunohistochemistry, were 18-fold enriched compared with unelutriated dispersed cells. Somatostatin release from cultured cells was expressed as a percent of the somatostatin released by a specific stimulus in control cells. Under basal conditions release of somatostatin was 2.3 +/- 0.6% of the total cell content. Epinephrine (1 microM) and cholecystokinin octapeptide (10 nM) increased somatostatin release to 6.98 +/- 1.25 and 10.72 +/- 1.64%, respectively. Carbachol (1 microM) completely inhibited somatostatin release stimulated by epinephrine and reduced cholecystokinin octapeptide-stimulated release to 75% of control levels. Carbachol inhibition of the response to both epinephrine and cholecystokinin octapeptide was totally prevented by 5 h of treatment of the cells with pertussis toxin (300 ng/ml). Somatostatin release in response to the diterpene forskolin (10 microM), dibutyryl cAMP (300 microM), the phorbol ester beta-phorbol 12-myristate 13-acetate (0.1 microM), and the calcium ionophore A23187 (1 microM) was also inhibited by carbachol and prevented by pertussis toxin pretreatment. The ADP-ribosylase inhibitor isonicotinamide (1 mM) selectively blocked the effect of pertussis toxin without altering other stimulatory or inhibitory responses. These data are consistent with the view that carbachol inhibits somatostatin release at guanyl nucleotide-binding protein and/or another pertussis toxin-sensitive site. PMID- 2902803 TI - Postprandial celiac and superior mesenteric blood flows in conscious dogs. AB - Celiac and superior mesenteric arterial blood flows were measured simultaneously in conscious beagle dogs. The responses to food were completely different between the two arteries. Celiac flow increased quickly to 180-200% of the control 2 min after food but started to decline rapidly to preprandial levels, though greater than 90% of food was still in the stomach. It remained at preprandial levels over the next 1-6 h. Superior mesenteric flow increased gradually in 20-50 min (peak: 230%) and remained above the control levels for 3-6 h. The celiac response was inhibited by vagal block, hexamethonium, and gastric mucosal anesthesia by oxethazaine but not by atropine, phenoxybenzamine, or propranolol. Postprandial superior mesenteric hyperemia was blocked by mucosal anesthesia and was reduced by atropine by 80%. Ganglionic or adrenergic blockades were without effect. It is concluded that the celiac peak response to food is mediated by a nonadrenergic, noncholinergic vagal reflex in conscious dogs. Extrinsic nerves probably play little part in the postprandial increase of superior mesenteric flow. PMID- 2902804 TI - NE turnover in genetically hypertensive rats of Lyon strain. I. Brain nuclei. AB - Several indirect evidences of alterations in the central catecholaminergic structures were obtained in genetically hypertensive rats. Because they could be of pathogenetic value, we measured, in the present work, the in vivo turnover (TO) of norepinephrine (NE) in brain areas of 5- and 22-wk-old genetically hypertensive (LH) rats of the Lyon strain, and their simultaneously selected normotensive (LN) and low blood pressure (LL) controls. Among the changes observed, the increased TO of NE in the A2 and A6 regions of 5-wk-old LH rats and its decrease in the posteroventral hypothalamic nucleus of 22-wk-old LH animals appeared likely to compensate for hypertension. On the contrary, the decreased TO of NE in the anterior hypothalamic nucleus observed at 5 wk and in the A6 and A1 areas at 22 wk of age in LH rats could participate in the development or the maintenance of hypertension. Above all, it was postulated that the increased TO of NE found in the A7 region of 5-wk-old LH rats could play a primary role in the pathogenesis of hypertension in the Lyon model. PMID- 2902805 TI - Regional hemodynamic responses to adrenoceptor antagonism in conscious rats. AB - Changes in blood pressure and renal, mesenteric, and hindquarters vascular resistances were measured in conscious Long-Evans and Brattleboro (vasopressin deficient) rats in response to sequential, continuous administrations of prazosin and idazoxan in the absence or presence of ICI 118551 (beta 2-adrenoceptor antagonist) or propranolol. The large transient hypotensions elicited by prazosin and, subsequently, by idazoxan were associated with renal and hindquarters vasodilatations in both strains of rat. In Brattleboro rats, prazosin also elicited mesenteric vasodilatation. Pretreatment with ICI 118551 reduced the initial hypotensive effects and hindquarters vasodilatations elicited by prazosin and idazoxan, but the hemodynamic effects of prazosin were not significantly affected by propranolol. These results are consistent with propranolol antagonizing beta 1-adrenoceptor-mediated effects on the heart and the renin angiotensin system that act to offset a beta 2-adrenoceptor-mediated vasodilatation, which contributes to the effects elicited by alpha-adrenoceptor antagonism. Hemodynamic responses to captopril and d(CH2)5DAVP (in Long-Evans rats) in the presence of adrenoceptor antagonists were consistent with a major cardiovascular role of the renin-angiotensin system and a less overt role of vasopressin until the latter system was blocked. PMID- 2902806 TI - Positive inotropic action of novel vasoconstrictor peptide endothelin on guinea pig atria. AB - Endothelin (ET), a novel 21-amino acid peptide isolated from the culture supernatant of porcine aortic endothelial cells, has been shown to be the most potent of all known vasoconstrictor substances. The purpose of the present study was to investigate the effects and the mode of actions of ET on the heart. ET exerted a positive inotropic effect in a dose-dependent manner on the electrically driven left atria of guinea pigs. The ET-induced response was of slow onset and characteristically long lasting. The half-maximal effective dose of the ET-induced response was about 1 nM, indicating that ET is one of the most potent cardiotonic substances. The response was presumably caused through direct actions of ET on the myocytes, since adrenergic, histaminergic, and serotonergic antagonists showed no effect on the response. The dose-response relationship of ET for the positive inotropic effect was displaced to the right in a parallel fashion by 0.3 microM nicardipine. In the left atria depolarized with 22 mM KCl, ET produced gradually increasing contractions in conjunction with the slow response action potentials in response to the electrical pacing. These results suggest that the ET-induced response on the left atria is intimately related to the influx of extracellular Ca2+. PMID- 2902807 TI - Movement of Entamoeba histolytica trophozoites in rat cecum and colon intact mucus blankets and harvested mucus gels. AB - Entamoeba histolytica trophozoites were centrifuged into mucus gels harvested from in vivo loops of rat cecum and proximal colon. Frank ameba movement was not detected in the colonic mucus, but attenuated motility was measured in the cecal mucus. The harvested rat cecal mucus had significantly lower apparent viscosity and neutral glycoprotein concentration values than the colonic mucus. A shape factor method was developed to assess the motility of amebae in mucus gels and intact mucus blankets. Shape factor data obtained from harvested mucus gel and intact mucus blanket experiments indicated that such mucus severely attenuated trophozoite movement with the attenuation being greater with colonic than with cecal mucus. Entamoeba trophozoites are known to be able to generate a pseudopod force of 3.3 x 10(-6) Newtons. Latex microspheres of the size range of Entamoeba trophozoites were forced through cecal and colonic mucus gels under gravity. Colonic mucus gels could withstand a force of 3.3 x 10(-6) Newtons while cecal mucus could not, suggesting that the ameba movement that was observed in cecal mucus involved mechanical penetration of the mucus by the ameba pseudopodia and did not require prior gel dissolution by Entamoeba enzymes. PMID- 2902808 TI - [Effect of the combined use of benzodiazepine preparations and alcohol on fetal development in an experiment]. PMID- 2902809 TI - Mosquito-borne diseases in Alabama. PMID- 2902810 TI - Large cell mycosis fungoides at the tumor stage. Unusual T8, T4, T6 phenotypic expression. AB - We report a case of mycosis fungoides in a 52-year-old woman with a huge skin tumor on her thigh in which the predominant cells were lymphoblastic and histiocytic large cells. The neoplastic cells showed strong suppressor and helper T-cell subset markers, and were partially positive for the cortical thymocyte (OKT6) subset marker. PMID- 2902811 TI - Esmolol in the uncontrolled hypertensive patient. PMID- 2902812 TI - [Vecuronium bromide: modification of its pharmacodynamics by etomidate, cimetidine and ranitidine]. AB - After obtaining their informed consent, 60 patients (ASA groups I or II), 18 to 60 years of age were randomly allocated to six groups of 10 persons each. Anesthesia was induced in groups 1, 4, 5 and 6 with 2-3 mg kg-1 thiopentone and in groups 2 and 3 with 0.2-0.3 mg kg-1 etomidate. 20 min before induction, patients in groups 3 and 5 received 5 mg kg-1 cimetidine, and patients in group 6 received 1.25 mg kg-1 ranitidine. Induction of anesthesia was supplemented by 0.002 mg kg-1 fentanyl and 0.01 mg kg-1 lormetazepam. After beginning neuromuscular monitoring, 0.08 mg kg-1 vecuronium was injected and the intubation accomplished when the first twitch of the train of four (TOF) was suppressed of a rate greater than 90%. The anesthesia was maintained with supplemental doses of 0.002 mg kg-1 fentanyl and 0.01 mg kg-1 lormetazepam, if necessary, and the use of a nitrous oxide/oxygen mixture (2.4:1.6 l min-1). A train of four supramaximal nerve stimuli was applied to the ulnar nerve proximal to the wrist and the twitch responses were electrically recorded on the hypothenar musculature (Relaxograph, Datex). The frequency of the train was 2 Hz with an interval of 20 s between trains. The time from the injection of vecuronium to several degrees of neuromuscular recovery was statistically significantly prolonged after 5 mg kg-1 cimetidine (groups 3 and 5) in comparison to the other groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902813 TI - [Benzodiazepine antagonism by RO 15-1788: psychometric, hormonal and biophysical parameters]. AB - Ro 15-1788, a selective benzodiazepine (BZD) antagonist, is known to precipitate withdrawal reactions in BZD-pretreated animals. We examined whether a high dose of Ro 15-1788 can precipitate withdrawal reactions relating to behavior and changes in the stress-hormone plasma levels after acute BZD treatment in man. On two consecutive days, 15 min and 24 h respectively after a single treatment with either lormetazepam (0.06 mg/kg: LMZ group), flunitrazepam (0.03 mg/kg: FNZ group) or placebo (PLA group), 18 healthy volunteers received two injections of Ro 15-1788 (0.01 mg/kg). Behavioral responses (mood changes, anxiety), cortisol and prolactin plasma levels, and physiological parameters were examined. In all groups there were only slight changes in the circulation parameters. Minor anxiety reactions were seen after Ro 15-1788, which occurred the 1st day in the PLA group and the 2nd day in the BZD groups. Depression was noted especially in the FNZ group after both injections of Ro 15-1788. The physiological morning decrease in cortisol plasma level was influenced on the 1st day in the LMZ group (2 volunteers showed high plasma levels) and the 2nd day in the FNZ group: a slight increase of cortisol plasma level was measured after the 2nd injection of Ro 15-1788. Prolactin plasma levels arose immediately after LMZ injection and continued to increase after Ro 15-1788 injection. No increase in prolactin plasma levels was found in the other groups or in the LMZ group after the 2nd challenge by Ro 15-1788.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902814 TI - Heterogeneities of the islets in the rabbit pancreas and the problem of "paracrine" regulation of islet cells. AB - In addition to "external" signals conveyed by the circulation or the nervous system, the pancreatic islets obviously are regulated also by "internal" (intra islet) signals, e.g. by the islet hormones: insulin (B-), glucagon (A-), and somatostatin (D-) cells are able to affect the secretion of the heterologous cell types. It is, however, unclear whether this functional cooperation between islet cells occurs by an intercellular route (paracrinia sensu strictore), by intra islet "portal" vessels, or by the systemic circulation. These likely interactions are limited by islet anatomy. To identify the anatomical basis for the mutual functional relationships between the islet cells, islets of Langerhans in the rabbit pancreas were completely analyzed in immunostained serial semithin (0.5 micron) sections. The islets were found to be largely heterogenous. They were classified in three basic types: a) polycellular islets, composed of all established endocrine cells, and including two subtypes of islets, b) bicellular islets, containing only B- and A-cells or B- and D-cells, and c) monocellular islets, exclusively made up of B-cells. Concerning the modes of paracrine regulation of islet cells, the findings suggest primarily an endocrinous route of transport of the islet peptides to heterologous endocrine cells. The corresponding functional cooperation between islet cells probably is mediated rather by the systemic circulation than by intra-islet portal vessels. PMID- 2902815 TI - A comparative study of the effects of non-union of testis and epididymis and cryptorchidism on testicular development and spermatogenesis in the rat. AB - Malunion of testis and epididymis is a congenital anomaly of human undescended testicles which may be of considerable clinical importance. In an experimental model in rat the effects of early disconnection of testis and epididymis (16 days) on testicular development have been testis and puberty. The results are compared with corresponding effects of cryptorchidism and sham-operation. The testes were weighed, and the relative proportions of haploid, diploid and tetraploid cells were quantified by DNA flow cytometry. The histology was evaluated by light and electron microscopy. The non-union operated testes showed a close to normal weight development until about 40 days of age, whereafter a decline occurred. The progression of the maturation division was only slightly reduced at 30 and 37 days of age, but later the spermatogenesis was significantly inhibited. At 58 days of age the maturation division had practically ceased in non-union operated testes. In cryptorchid animals the onset and progression of maturation divisions were almost totally depressed, and only traces of haploid cells were seen in some specimens. The transient increase in tetraploid cells, reflecting primary spermatocytes seen at about 30 days during normal testicular development, was neither depressed in non-union operated nor in cryptorchid animals. This indicates that the major block in spermatogenesis in both situations is at the stage of the primary spermatocytes. At 58 days of age the testicular histology was similar in non-union operated and cryptorchid testicles with many tubular sections showing only Sertoli cells. Scattered and partly degenerated germinal cells were seen in some sections. No histological signs of increased intratubular fluid pressure were detected, suggesting that pressure atrophy is not decisive for the reduced spermatogenesis in non-union operated gonads. PMID- 2902816 TI - Uptake and excretion of vecuronium bromide and pancuronium bromide in the isolated perfused rat liver. AB - Using the isolated perfused rat liver preparation, the disappearance from the perfusate and the excretion in the bile of vecuronium bromide and pancuronium bromide and their metabolites were followed for 2 h after the addition of 1 mg of either drug to the perfusate. In addition, the rate of change of the hepatic content of these two compounds was calculated by serially subtracting the amount of the compound and the metabolites in the bile and in the perfusate from the dose of drug added to the perfusate. It was found that, whereas the concentration of pancuronium in the perfusate declined slowly and monoexponentially, vercuronium concentration in the perfusate declined rapidly in a biexponential manner. No metabolites of either drug were detected in the perfusate. Approximately 40% of the injected dose of vecuronium was excreted in the bile as unchanged vecuronium and another 30% as the 3-hydroxy metabolite. No other metabolites of vecuronium were found in the bile. In total only about 7% of pancuronium (unchanged) was collected in the bile by the end of the experiment. It is concluded that, in comparison to pancuronium, the rat liver takes up large amounts of vecuronium rapidly, half of which is eliminated as unchanged vecuronium and half as the 3-hydroxy derivative. A small amount of vecuronium or its 3-hydroxy metabolite is returned to the perfusate from the liver. Some possible mechanisms underlying these differences are discussed. PMID- 2902817 TI - Prevalence of fimbrial antigens and enterotoxins in nonclassical serogroups of Escherichia coli isolated from newborn pigs with diarrhea. AB - Ninety-nine nonclassical serogroups isolated from newborn pigs with neonatal diarrhea were tested for fimbrial antigens F4(K88), F5(K99), F6(987P), F41, and F165, and for heat-labile enterotoxin, heat-stable enterotoxin a (STa), heat stable enterotoxin b, verocytotoxin, and cytolethal-distending toxin. Thirty-two strains, belonging mostly to serogroups O64:K"V142,", O9:K103, and O20:K101, were F5-positive and usually produced STa, although 5 strains produced only heat stable enterotoxin b. Fifteen strains, belonging mostly to serogroups O64:K"V142" and O20:K101, were F41 positive and usually produced STa. Twenty-three stains, belonging mostly to serogroups O64:K"V142," O9:K103, and O20:K101, were F6 positive and usually produced STa. Several strains produced more than one fimbrial antigen, either F5 and F41, F5 and F6, F6 and F41, F6 and F165, or F5, F6, F41, and F165. None of the strains produced heat-labile enterotoxin, verocytotoxin, or cytolethal-distending toxin. The indirect immunofluorescence test was much more sensitive than was the slide agglutination test for the detection of each of the fimbrial antigens F5, F6, F41, and F165 on strains grown in vitro. The production of F6 by certain strains for which only a low proportion of cells were F6-positive in vitro, as demonstrated by immunofluorescence, was confirmed by experimental infection of newborn pigs. PMID- 2902818 TI - [Adenocarcinoma of the amphicrine cells of the pancreas. Histopathology and pathogenetic hypotheses]. PMID- 2902819 TI - [Spinal analgesia: an alternative pharmacologic technic to neuroleptics]. PMID- 2902820 TI - Role of Ti/CD3, Thy-1, and Ly-6 in cytolytic T-cell activation analyzed with Ti loss variants. PMID- 2902821 TI - Immunocytochemical detection of a resistance-associated glycoprotein in tissue culture cells, ascites tumors and human tumor xenografts by Mab 265/F4. AB - The aim of this investigation was to find out whether resistant cells of different tumors can be detected immunocytochemically by the streptavidin-biotin peroxidase-complex method using the monoclonal antibody 265/F4. This antibody was prepared against the membrane P-glycoprotein of Mr 170 kd from colchicine resistant CHO cells. For this purpose the acquired resistance of tissue culture cells, ascites tumors and the acquired and inherent resistance of human lung carcinoma xenografts were analyzed. Doxorubicin-resistant S180 cells, daunorubicin-resistant L1210 cells and vincristine-resistant human epidermoid lung carcinoma xenografts showed an intense positive reaction with the monoclonal antibody. In contrast, no specific immunoreactivity was observed with parental (sensitive) tumor cells. These data could eventually provide a prognostic tool for the detection of resistant human tumor cells. PMID- 2902822 TI - Reduction of DNA repair efficiency during the initial phase of rat liver carcinogenesis. AB - Chemically induced DNA fragmentation and unscheduled DNA synthesis (UDS) were determined in hepatocyte primary cultures (HPC) obtained from the entire liver during the development of hyperplastic lesions induced in rats by the following treatment: 200 mg/kg i.p. of N-nitrosodiethylamine (DEN) on day 0; 2 ml/kg i.g. of CCl4 on day 21; dietary administration of 0.02% 2-acetylaminofluorene (2-AAF) during the 3rd and the 4th week, and of 0.05% phenobarbital (PB) from the 6th week. At 4, 5, 6, and 7 weeks after DEN injection, the level of DNA fragmentation elicited by either the activation-independent carcinogen methyl methanesulfonate (MMS) or the activation-dependent carcinogen N-nitrosodimethylamine (DMN) was significantly lower than that in HPC from age-matched normal rats. In the same HPC, a statistically significant decrease was observed in the capability of repairing DNA damage induced by MMS, while the reduction of the DNA repair efficiency did not reach the level of significance after exposure to DMN. PMID- 2902823 TI - Restriction fragment length polymorphism and activation of c-Ha-ras gene in urothelial cancer. AB - The human c-Ha-ras gene shows restriction length polymorphism (RFLP) due to the variable tandem repetition (VTR) of DNA sequences in the 3'-flanking region. It was suggested that RFLP of the c-Ha-ras gene may be useful in detecting individuals at risk of cancer. In vitro studies showed transcriptional enhancer and promoter activities in the VTR region. In some human tumors, the loss of one c-Ha-ras allele is observed. We discuss here the possible role of VTR and allelic deletion of the c-Ha-ras allele in primary human cancers in relation to c-Ha-ras expression, and the usefulness of c-Ha-ras RFLP in the risk assessment of urothelial cancer. PMID- 2902824 TI - Inflammatory lesions of peripheral nerve in a patient with human T-lymphotropic virus type I--associated myelopathy. AB - In a patient with tropical spastic paraparesis associated with a positive titer for human T-lymphotropic virus type I, electrophysiological study detected a mixed, axonal and demyelinating, multifocal neuropathy. Perineural and perivascular infiltrates, moderate axon loss, wallerian degeneration, and demyelinating lesions of isolated fibers were present in the nerve biopsy specimen. These inflammatory lesions resembled those found in the central nervous system of patients with tropical spastic paraparesis. PMID- 2902825 TI - Activated T-lymphocytes with polyclonal gammopathy in patients with human T lymphotropic virus type I--associated myelopathy. AB - Human T-lymphotropic virus type I (HTLV-I)--associated myelopathy (HAM) has been shown to be closely related to HTLV-I infection. However, the mechanism by which this disease occurs after infection with HTLV-I is still obscure. We found that HAM patients have unusually high proportions of CD4+ HLA-DR+ cells, CD8+HLA-DR+ cells, OKT9+ cells, and CD38(OKT10)+ cells in their peripheral blood, all of which suggest the presence of activated T-lymphocytes. Antibody titer against HTLV-I was much higher in HAM patients than in HTLV-I carriers without evident neurological disease (p less than 0.01). Polyclonal gammopathy was also observed in most HAM patients, and 6 of 10 patients were positive for rheumatoid factor. These observations, coupled with the previous observation that corticosteroid therapy improves clinical symptoms in some patients, make it likely that continuous activation of the immune system, initiated by HTLV-I infection, plays a key role in the pathogenesis of HAM. PMID- 2902826 TI - Genetic organization and biogenesis of adhesive fimbriae of Escherichia coli. AB - The genetic organization of the determinants of type 1, K88ab, K99 fimbriae and P(pap)pili of Escherichia coli is presented. The functions of the various gene products are described and a model for the process of fimbriae biogenesis is presented and discussed. PMID- 2902827 TI - Glutamine synthetase specific activity and protein concentration in symbiotic Anabaena associated with Azolla caroliniana. AB - Glutamine synthetase (GS) is the primary NH4+ assimilating enzyme of cyanobacteria. The specific activities and cellular protein concentration of GS in symbiotic cyanobacteria associated with the water fern Azolla caroliniana were determined and compared to free-living cultures of Nostoc sp. strain 7801, a strain originally isolated from symbiotic association with the bryophyte Anthoceros punctatus. Both the in vitro specific activity and concentration of GS in symbiotic cyanobacteria separated from A. caroliniana were approximately 3 fold lower than the free-living Nostoc sp. strain 7801 culture. These results imply depressed synthesis of GS by the symbiont associated with A. caroliniana. PMID- 2902829 TI - Temperature dependence and mercury inhibition of tonoplast-type H+-ATPase. AB - The effects of changing temperature on ATP hydrolysis and proton pumping associated with the H+-ATPase of tonoplast membrane vesicles isolated from the maize root microsomal fraction were determined. In the range 5 to 45 degrees C, the maximal initial rate of ATP hydrolysis obeyed a simple Arrhenius model and the activation energy determined was approximately 14 kcal/mol. On the other hand, the initial proton pumping rate showed a bell-shaped temperature dependence, with maximum activity around 25 degrees C. Lineweaver-Burke analysis of the activities showed that the Km of ATP hydrolysis, unlike that of proton pumping, was relatively insensitive to temperature changes. Detailed kinetic analysis of the proton pumping process showed that the increase in membrane leakage to protons during the pumping stage constituted a major reason for the decreased transport. Nitrate-sensitive ATPase activities of the tonoplast vesicles were found to be inhibited by the presence of micromolar concentrations of Hg2+. The proton pumping process was more sensitive to the presence of Hg2+. Double-reciprocal analysis of kinetic data indicated that Hg2+ was a noncompetitive inhibitor of proton pumping but was an uncompetitive inhibitor of ATP hydrolysis. Further kinetic analysis of Hg2+ effects revealed that the lower proton transport did not result from enhanced membrane leakage but rather from reduced coupling between H+ pumping and ATP hydrolysis. PMID- 2902828 TI - Activation of Clostridium perfringens spores under conditions that disrupt hydrophobic interactions of biological macromolecules. AB - The effect of hydrophobic interactions on the activation of C. perfringens NCTC 8679 spores was examined by heating spores under conditions that modify the hydrophobic properties of biological macromolecules. After the activation treatment and a washing procedure, germination was determined by measuring the decrease in optical density of spores suspended in an enriched germination medium. Activation was inhibited for spores that were treated under conditions that strengthen hydrophobic interactions, i.e., a decrease in pH or the presence of structure-stabilizing neutral salts. Activation was enhanced by treatment under conditions that disrupt hydrophobic interactions, i.e., an increase in pH or the presence of urea, dibucaine, or denaturing neutral salts. A deactivation treatment with the antichaotropic salt (NH4)2SO4 reversed activation by the chaotropic salt CaCl2 and to a lesser extent reversed activation by sublethal heat (75 degrees C) or urea. Most treatments that enhanced activation increased spore injury at higher temperatures, which resulted in decreased germination. However, (NH4)2SO4 and a decrease in pH from 5.6 to 3.8, which inhibited activation, also favored injury. The results suggest that activation involves a conformational change of a spore protein(s) through weakening of hydrophobic molecular forces and that activation and injury occur at different spore sites. PMID- 2902830 TI - [Therapeutic approaches for multidrug resistance]. AB - One of the major problems in cancer chemotherapy is the development of drug resistance during treatment. In the treatment of tumors with antitumor agents, tumor cells can acquire resistance to the drugs. This type of resistance is called as acquired drug resistance and the acquired drug resistances is a major factor for limiting the clinical use of antitumor agents. The elucidation of the resistance mechanisms has progressed well recently owing to the application of cellular and molecular techniques in addition to the usual biological and biochemical techniques. In this article, the mechanisms of cellular resistance, especially those of multidrug resistance at a molecular level, and possible approaches to overcoming drug resistance are described and discussed. PMID- 2902831 TI - [The multidrug-resistance gene MDR1]. AB - MDR1 gene encodes a membrane glycoprotein (P-glycoprotein) that acts as a energy dependent pump to transport antitumor drugs out of the cells. P-glycoprotein, 1280 amino acids long, consists of two homologous parts of approximately equal length. The protein has binding sites for ATP, antitumor drugs and calcium channel blockers. MDR1 gene is expressed tissue-specific in human normal adrenal, kidney, liver and colon. The normal function and transcriptional regulation of this gene are also discussed. PMID- 2902832 TI - [Detection of multidrug resistant phenotype in leukemia and lymphoma by monoclonal antibodies]. AB - Two monoclonal antibodies, MRK16 and MRK20 that recognize P-glycoprotein and P-85 kd protein on the surface of adriamycin (ADM) resistant cells, respectively, were tested for the reactivity with 40 cultured leukemia/lymphoma cell lines. F(ab')2 form is essential to avoid false reaction through Fc gamma-R. Drug sensitivity of 19 representative cell lines were also examined in vitro. From this study, it was found that these cell lines were classified into 4 groups. Group 1 (4 cell lines) was insensitive to ADM, mitoxantron (MXT), etoposide (VP-16) and vincristine (VCR), and reactive to MRK16 and MRL20. Group II (1 cell line) was insensitive to the 4 drugs, but not reactive to both antibodies. Group III (3 cell lines) was insensitive to ADM, MXT and VP-16, but sensitive to VCR, and reactive to MRK20, but not to MRK16. Group IV (all other cell lines) was sensitive to these drugs, and not reactive to both antibodies. From these results, MRK16 detects P glycoprotein-associated multidrug resistance (MDR), while MRK20 does P 85-kd associated another type MDR (cross resistance to ADM, MXT and VP-16, but not to VCR). MRK20 reacted with monocytes, but MRK16 did not with any WBC type. One hundred and ninety eight clinical samples obtained from blood cancer were tested for the reactivity with MRK16. MRK16 did not react with any of 98 samples obtained before treatment, but did with 9 of 100 obtained at relapse or refractory stage after chemotherapy. The results indicate that MRK16 is useful to detect drug resistance phenotype of leukemia and lymphoma. PMID- 2902833 TI - [Determination of various tumor markers, with special reference to sialyl SSEA-1 antigen in lung cancer]. AB - Tumor markers including sialyl SSEA-1 antigen (SLX) were measured in 77 patients with lung cancer and 116 patients with benign respiratory diseases. Increased levels of serum SLX were observed in 57.6% (19/33) of adenocarcinoma of the lung, and an overall positive rate was 42.9% (33/77) in lung cancer cases. The false positive incidence of SLX in the sera from the patients with non-malignant diseases was as low as 8.6%. Among other tumor markers determined, serum CA 19-9, CEA had a relatively high positive rate, but the false positive incidence were not low. In cases of poor prognostic cases of with adenocarcinoma of the lung, SLX levels became levels higher than the previous ones, but not in cases of other cell types were not. Not only in the patients with lung cancer but also in those with benign respiratory diseases such as bronchiectasis and lung fibrosis, high levels of SLX seemed to suggest poor prognosis. These results indicate that SLX may contribute for monitoring and prognosis of the cases of lung cancer and other respiratory diseases. PMID- 2902834 TI - Heightened cutaneous reactions to mosquito bites in patients with acquired immunodeficiency syndrome receiving zidovudine. AB - Three patients with acquired immunodeficiency syndrome noted changing cutaneous reactions to mosquito bites one to three months after starting zidovudine therapy. Enhanced T-cell function is one possibility for the heightened response to mosquito bites in these patients. PMID- 2902835 TI - The human peripheral Ts lymphocytes are endowed with a heat stable E receptor. PMID- 2902836 TI - Glutathione content and gamma-glutamyltranspeptidase activity in squamous cell head and neck cancer xenografts. AB - Drug resistance is a major problem in chemotherapy of squamous cell head and neck cancers (SCHNC). Since glutathione (GSH) plays a crucial role in mediating tumor cell resistance against various toxic insults, GSH metabolism in SCHNC xenografts was investigated. Xenografts from lymph node metastases contained markedly higher GSH concentrations compared with those derived from the corresponding primary lesions. After subcurative chemotherapy with cisplatin (DDP), a significant increase of both GSH levels and gamma-glutamyltranspeptidase activity (gamma-GT) was gained in tumor HT1M. Tumor HT3M showed high concentrations of GSH and gamma GT, although these latter concentrations did not increase following chemotherapy with DDP. These findings suggest a possible impact of GSH metabolism on both the formation of metastases and the phenomenon of drug resistance in SCHNC. PMID- 2902837 TI - Undescended testis: how history and examination may influence treatment. AB - This paper reports a prospective study of 114 boys with 126 undescended testes. The aims were to identify the position of the testis in the first year of life, to document cases of apparent ascent of the testes following a scrotal position in infancy, and to determine whether knowledge of the position of the testis in infancy might be used as a guide in later management. In 92 instances the position of the testis at birth, at 6 weeks and at 1 year of age was recorded; 84 were considered undescended and eight were in the scrotum. There was no clear indication of the position of the testis in the remaining 34. When the position of the testis was known to be undescended from birth to the end of the first year, response to hormonal therapy was disappointing. However, when there was a history of prior descent or when there was no clear information about the position in the first year of life, response to hormonal therapy was rewarding (57%) and this therapeutic modality is recommended prior to surgery for this group of patients. PMID- 2902838 TI - Benzodiazepine use in a rural general practice population. AB - This study investigates the prevalence and pattern of benzodiazepine use in an isolated Australian rural general practice setting. Some clinical features of psychological dependence were also examined. Data were obtained from 771 patients attending each of two general practices over a five-day period. The results indicated that 11.3% of the sample had used a benzodiazepine in the preceding four weeks and that 82% of these had been regular users for over six months. Prevalence increased with age and 36.5% of patients over the age of 70 were using benzodiazepines. Features suggesting some degree of psychological dependence were found in over 50% of users. The findings illustrate the extensive and prolonged use of benzodiazepines and raise questions about overuse and dependence, particularly in the elderly. PMID- 2902840 TI - [Stability of repetitive DNA sequences in cadaver tissues]. PMID- 2902839 TI - Effects of lisuride and quinpirole on convulsions induced by hyperbaric oxygen in the mouse. AB - Two ergot derivatives, lisuride and quinpirole, were examined for their ability to antagonize hyperbaric oxygen-induced (5 ATA O2) convulsions in mice. Significant protection was obtained by lisuride (25-400 micrograms.kg-1, i.p.) and quinpirole (100-200 micrograms.kg-1, i.p.). The efficacy was found to be about 50% of the protection obtained by diazepam (4 mg.kg-1, i.p.). Both lisuride and quinpirole significantly reduced rectal temperature at all doses administered. In separate experiments, at normal atmospheric conditions, all drugs to some extent reduced estimated respiratory minute volume. Taking these effects into account, lisuride is considerably more active as an anticonvulsant than quinpirole. PMID- 2902841 TI - [Isolation of high molecular weight DNA from a 14-day-old immersed cadaver]. PMID- 2902842 TI - [Determination of restriction fragment length polymorphism in microscopically verified sperm findings]. PMID- 2902843 TI - [Characteristics of drunkeness at the rudder and drinking habits of motor boat drivers in Helsinki]. PMID- 2902844 TI - DNA sequence of a gene cluster coding for subunits of the F0 membrane sector of ATP synthase in Rhodospirillum rubrum. Support for modular evolution of the F1 and F0 sectors. AB - A region was cloned from the genome of the purple non-sulphur photobacterium Rhodospirillum rubrum that contains genes coding for the membrane protein subunits of the F0 sector of ATP synthase. The clone was identified by hybridization with a synthetic oligonucleotide designed on the basis of the known protein sequence of the dicyclohexylcarbodi-imide-reactive proteolipid, or subunit c. The complete nucleotide sequence of 4240 bp of this region was determined. It is separate from an operon described previously that encodes the five subunits of the extrinsic membrane sector of the enzyme, F1-ATPase. It contains a cluster of structural genes encoding homologues of all three membrane subunits a, b and c of the Escherichia coli ATP synthase. The order of the genes in Rsp. rubrum is a-c-b'-b where b and b' are homologues. A similar gene arrangement for F0 subunits has been found in two cyanobacteria, Synechococcus 6301 and Synechococcus 6716. This suggests that the ATP synthase complexes of all these photosynthetic bacteria contain nine different polypeptides rather than eight found in the E. coli enzyme; the chloroplast ATP synthase complex is probably similar to the photosynthetic bacterial enzymes in this respect. The Rsp. rubrum b subunit is modified after translation. As shown by N-terminal sequencing of the protein, the first seven amino acid residues are removed before or during assembly of the ATP synthase complex. The subunit-a gene is preceded by a gene coding for a small hydrophobic protein, as has been observed previously in the atp operons in E. coli, bacterium PS3 and cyanobacteria. A number of features suggest that the Rsp. rubrum cluster of F0 genes is an operon. On its 5' side are found sequences resembling the -10 (Pribnow) and -35 boxes of E. coli promoters, and the gene cluster is followed by a sequence potentially able to form a stable stem-loop structure, suggesting that it acts as a rho-independent transcription terminator. These features and the small intergenic non-coding sequences suggest that the genes are cotranscribed, and so the name atp2 is proposed for this second operon coding for ATP synthase subunits in Rsp. rubrum. The finding that genes for the F0 and F1 sectors of the enzyme are in separate clusters supports the view that these represent evolutionary modules. PMID- 2902845 TI - Regulation by insulin of glucose metabolism in mammary gland of anaesthetized lactating rats. Stimulation of phosphofructokinase-1 by fructose 2,6-bisphosphate and activation of acetyl-CoA carboxylase. AB - The effect of insulin on glucose metabolism in mammary gland was studied by the euglycaemic/hyperinsulinaemic-clamp technique. Measurement of metabolite concentrations and enzyme activities in the mammary gland suggests two sites of action of insulin: phosphofructokinase-1 and acetyl-coA carboxylase. The increase in phosphofructokinase-1 activity could be linked to the 2-fold increase in fructose 2,6-bisphosphate concentration, since no change in maximal activity and in sensitivity of the enzyme toward fructose 6-phosphate was detected in vitro. PMID- 2902846 TI - The effect of non-esterified fatty acids on the proton-pumping cytochrome c oxidase reconstituted into liposomes. AB - Bovine heart cytochrome c oxidase was reconstituted in phospholipid vesicles, and the effect of different non-esterified fatty acids (NEFA) was studied on its proton pump and on the proton permeability of the vesicles. Neither parameter appeared to be affected by concentrations of NEFA known to uncouple oxidative phosphorylation (10 microM). Also the permeability for K+ was not affected by them. The fatty acids caused an increase in the rate of electron transfer in the absence, but not in the presence, of uncoupler and/or valinomycin [diminution of the respiratory-control index (RCI)]. The RCI of 8.7-7.5 was decreased to about 4.5 in the presence of 0.27-10 microM-NEFA. Oleic acid was not effective at the above concentrations. Subunit III-depleted enzyme preparations gave vesicles with an RCI of about 5.5, which was decreased to 4.5 in the presence of NEFA. With both native and subunit III-depleted oxidase the RCI was never decreased to the value of 1 by NEFA, as happens with classical protonophores. PMID- 2902847 TI - Tyrosine sulphation is not required for microvillar expression of intestinal aminopeptidase N. AB - The effect of 2,6-dichloro-4-nitrophenol (DCNP), an inhibitor of phenol sulphotransferases (EC 2.8.2.-), on the biosynthesis of aminopeptidase N (EC 3.4.11.2) was studied in organ-cultured pig intestinal mucosal explants. At 50 microM DCNP did not affect protein synthesis but it decreased incorporation of [35S]sulphate into aminopeptidase N and other major microvillar hydrolases by 70 85% compared with controls, indicating an inhibition of their post-translational tyrosine sulphation. In labelling experiments with [35S]methionine from 0.5 to 5 h, DCNP was tested for its possible influence on synthesis, processing and microvillar expression of aminopeptidase N, but no effect on any of these parameters could be detected. It can therefore be concluded that tyrosine sulphation is not required (for instance as a sorting signal) for the targeting of newly synthesized enzymes to the microvillar membrane. PMID- 2902848 TI - Fluazifop, a grass-selective herbicide which inhibits acetyl-CoA carboxylase in sensitive plant species. AB - Fluazifop is a grass-selective herbicide that appears to act by inhibiting fatty acid synthesis de novo in sensitive species. Results from four different types of experiment show that this inhibition is due to an action of fluazifop on acetyl CoA carboxylase and not on fatty acid synthetase. The acetyl-CoA carboxylase from sensitive barley (Hordeum vulgare), but not from resistant pea (Pisum sativum), is inhibited by the R stereoisomer, a finding that agrees with the herbicidal specificity of fluazifop. PMID- 2902849 TI - Gluconeogenesis in the amphibian retina. Lactate is preferred to glutamate as the gluconeogenic precursor. AB - The capacity for gluconeogenesis in the isolated amphibian retina was found to be approx. 70-fold greater with lactate than with glutamate as the gluconeogenic precursor, 1426 versus 21 pmol of glucose incorporated into glycogen/h per mg of protein. It was also found that 11-15% of the glucosyl units in glycogen are derived from C3 metabolites of the glycolytic pathway, suggesting that lactate is recycled within the retina. In concert with these metabolic observations, a full complement of the gluconeogenic enzymes was detected in retinal homogenates. These included: glucose-6-phosphatase, fructose-1,6-bisphosphatase, acetyl-CoA dependent pyruvate carboxylase and phosphoenolpyruvate carboxykinase. Agents that regulate the rate of gluconeogenesis in hepatic tissue were tested on the retina. At concentrations of glutamate and lactate that are presumed to be relevant physiologically, it was found that vasoactive intestinal peptide, ionophore A23187 and elevated [K+] each enhanced the rate of gluconeogenesis in Ringer containing 50 microM-glutamate, whereas in Ringer containing 8.5 mM-lactate these agents inhibited the rate of gluconeogenesis. Further, it was found that the classic gluconeogenic hormone glucagon inhibited gluconeogenesis in both glutamate- and lactate-containing Ringer. Retinal energy metabolism was found to be altered in lactate-containing Ringer, in that lactate production was suppressed completely. In addition, glycogen metabolism appeared to be dependent on increased cytosolic Ca2+ and was insensitive to increased retinal cyclic AMP. PMID- 2902850 TI - Glutathione replenishment capacity is lower in isolated perivenous than in periportal hepatocytes. AB - The zonal distribution of GSH metabolism was investigated by comparing hepatocytes obtained from the periportal (zone 1) or perivenous (zone 3) region by digitonin/collagenase perfusion. Freshly isolated periportal and perivenous cells had similar viability (dye exclusion, lactate dehydrogenase leakage and ATP content) and GSH content (2.4 and 2.7 mumol/g respectively). During incubation, periportal cells slowly accumulated GSH (0.35 mumol/h per g), whereas in perivenous cells a decrease occurred (-0.14 mumol/h per g). Also, in the presence of either L-methionine or L-cysteine (0.5 mM) periportal hepatocytes accumulated GSH much faster (3.5 mumol/h per g) than did perivenous cells (1.9 mumol/h per g). These periportal-perivenous differences were also found in cells from fasted rats. Efflux of GSH was faster from perivenous cells than from periportal cells, but this difference only explained 10-20% of the periportal-perivenous difference in accumulation. Furthermore, periportal cells accumulated GSH to a plateau 26 40% higher than in perivenous cells. There was no significant difference in gamma glutamylcysteine synthetase or glutathione synthetase activity between the periportal and perivenous cell preparations. The periportal-perivenous difference in GSH accumulation was unaffected by inhibition of gamma-glutamyl transpeptidase or by 5 mM-glutamate or -glutamine, but was slightly diminished by 2 mM-L methionine. This suggests differences between periportal and perivenous cells in their metabolism and/or transport of (sulphur) amino acids. Our results suggest that a lower GSH replenishment capacity of the hepatocytes from the perivenous region may contribute to the greater vulnerability of this region to xenobiotic damage. PMID- 2902852 TI - On the specificity of a cysteine proteinase from Entamoeba histolytica. AB - A cysteine proteinase has been isolated from the virulent strain HM1:IMSS of Entamoeba histolytica by two gel chromatography steps, ion exchange chromatography on DEAE-cellulose and affinity chromatography on organomercurial Sepharose. The purified proteinase was homogeneous, as judged by polyacrylamide gel electrophoresis in the presence and in the absence of sodium dodecyl sulphate, and was a monomeric protein with a relative molecular mass of Mr 27000 +/- 2000 possessing an N-terminal alanine. The enzyme was inhibited by natural and synthetic inhibitors against cysteine proteinases. Split experiments employing blocked and unblocked peptide analogues with -2-naphthylamide moieties indicate that the cleavability was enhanced by the presence of basic residues, such as arginine or lysine, near the acyl end of the substrate. With unblocked tetrapeptides as substrates, exopeptidase activity of the amebic enzyme required an arginine at the P2-position, lysine could not substitute for arginine. The protease was able to digest native collagen type I, with an initial attack at the alpha 2-chain of the molecule. PMID- 2902851 TI - Effect of oversulphated chondroitin and dermatan sulphate upon thrombin and factor Xa inactivation by antithrombin III or heparin cofactor II. AB - The kinetics of inhibition of human thrombin and Factor Xa by antithrombin III or heparin cofactor II were examined under pseudo-first-order conditions as a function of the concentration of naturally occurring oversulphated chondroitin and dermatan sulphates. The sulphated glycosaminoglycans (GAGs) studied were chondroitin sulphate D (CSD) (GlcA-2-SO4-GalNAc-6-SO4), chondroitin sulphate K (CSK) (GlcA-3-SO4-GalNAc-4-SO4), chondroitin sulphate H (CSH) (IdA-GalNAc-4,6 diSO4) and polysulphated dermatan sulphate (DPS) (IdA-2-SO4 or -3-SO4-GalNAc-4,6 diSO4). The data for the antithrombin III inhibition of thrombin showed a low degree of maximal potentiation of this interaction (congruent to 10-fold), which would appear to be characteristic of GAGs devoid of the high-affinity antithrombin III binding site. In contrast there was a greater potentiation of the inhibition of thrombin by heparin cofactor II with DPS showing an activity comparable to heparin in this interaction at a concentration two orders of magnitude lower than dermatan sulphate. DPS potentiated antithrombin III-Factor Xa interaction by 1200-fold, similar to that shown by high-affinity heparin of 6 kDa. The antithrombin III-Factor Xa interaction was potentiated by all other GAGs studied to a degree similar to that of heparin pentasaccharide with high affinity for antithrombin III. The findings suggest more stringent structural requirements for GAG stimulation of antithrombin-thrombin interaction than for antithrombin Factor Xa or heparin cofactor-thrombin interaction, which may also be of significance in physiological control of haemostasis. PMID- 2902853 TI - Gamma-glutamyl transpeptidase alterations in liver and serum induced by haloperidol. AB - Changes in the activity of the microsomal enzyme gamma-glutamyl transpeptidase (GGT) were examined in liver and serum following subacute and chronic haloperidol administration to rats. Haloperidol increased both serum and liver GGT levels. The enzymatic activity returned to baseline values on the sixth day after withdrawal of the drug. It is concluded that alterations in serum GGT levels may be expected during prolonged treatment of haloperidol, and that these alterations reflect enzyme induction in liver microsomes where the drug is entirely metabolized. PMID- 2902854 TI - Regulation of glutamine synthetase activity by phosphorylation instead of by adenylylation. AB - o-Phosphotyrosyl glutamine synthetase (P-GS) was isolated from highly adenylated glutamine synthetase (AMP-GS) purified from Mycobacterium phlei, by treatment with micrococcal nuclease. The physical characteristics of P-GS were quite similar to those of AMP-GS except for the UV-absorption spectrum. In either Mg2+- or Mn2+-dependent biosynthetic reactions, the kinetic properties, such as optimum pH, Vmax, and apparent Km for each of three substrates of P-GS, were found to be in good agreement with those of AMP-GS. The biosynthetic activity of P-GS was markedly increased after treatment with alkaline phosphatase similarly as in the deadenylylation of AMP-GS by snake venom phosphodiesterase treatment. These results revealed that repression of glutamine synthetase activity simply requires the phosphorylation of the tyrosyl residue, without recourse to adenylylation. PMID- 2902855 TI - Atrial natriuretic factor increases the magnitude of duodenal spontaneous phasic contractions. AB - The present investigation was designed to determine if atrial natriuretic factor relaxes non-vascular smooth muscle. Rather than cause a relaxation, atrial natriuretic factor induced a two-to-four fold enhancement in the amplitude of the spontaneous phasic contractions of duodenal longitudinal muscle. Dose-response curves revealed that ANF enhanced these contractions over a concentration range of 10 picomoles to 100 nanomoles with the ED50 at 1 nanomolar. The increased amplitude of contraction began within 30 seconds and was calcium-dependent. The increased force of contraction was associated with a three-fold increase in cyclic GMP levels and activation of particulate guanylate cyclase [E.C.4.5.1.2.]. Atrial natriuretic factor had its half-maximal [ED50] activation of guanylate cyclase at its 1 nM concentration while maximal enhancement was at its 100 nM concentration in duodenum, jejunum, and ileum. Atrial natriuretic factor did not stimulate adenylate cyclase [E.C.4.6.1.1.]. Thus, atrial natriuretic factor increases the force of the spontaneous phasic contractions of the small intestine which are calcium-dependent and associated with activation of the guanylate cyclase-cyclic GMP system. PMID- 2902856 TI - The increase in hepatic tyrosine aminotransferase activity by ethanol administration involves an acceleration of enzyme synthesis. AB - The present study was conducted to examine the nature of the increase in tyrosine aminotransferase (TAT) activity by acute ethanol administration. A significant rise in aminotransferase activity was observed as early as 1 hr after intact rats were gavaged with ethanol. Ethanol administration also increased TAT activity in adrenalectomized rats. Inhibition of ethanol metabolism by pyrazole administration had no effect on the ethanol-induced increase in TAT activity. Immunochemical analyses revealed that the enhancement of TAT activity in ethanol fed rats correlated with an increase in aminotransferase protein. Measurement of the rate of TAT synthesis showed that in ethanol-fed rats, [3H]leucine was incorporated into the aminotransferase protein at a higher rate than in controls by a factor which was similar to the enhancement in enzyme activity. Our findings indicate that an acceleration of TAT synthesis fully accounts for the increase in TAT activity during the early stage of enzyme induction. TAT induction by ethanol administration is not dependent upon an increase in adrenal corticosteroid production, nor does it require ethanol metabolism. PMID- 2902857 TI - Dermorphin analogs: resistance to in vitro enzymatic degradation is not always increased by additional D-amino acid substitutions. AB - Dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) and seven analogs were examined for their biostability towards rat brain homogenate; half-lives for the parent were 127 min and 48 min, respectively, with Gly4-Tyr5 cleavage confirmed by collection and identification of the N-terminal fragment. Surprisingly, several analogs with additional D-amino acid substitutions were cleaved more rapidly than the parent, suggesting the importance of remote secondary structural features for differential enzyme susceptibility. PMID- 2902858 TI - Discrepancies between the affinities of binding and action of the novel beta adrenergic agonist BRL 37344 in rat brown adipose tissue. AB - The novel brown adipose tissue (BAT) selective beta-adrenergic agonist, BRL 37344, is 31-fold more potent than (-)-isoproterenol in stimulating the respiratory rate of interscapular BAT fragments. BRL 37344 is also more potent (9 fold) than (-)-isoproterenol in stimulating adenylate cyclase activity of IBAT purified plasma membranes whereas, in the same preparation, it is 81-fold less potent than (-)-isoproterenol in competition displacement studies with the beta adrenergic ligand, [125I]cyanopindolol. We have previously demonstrated that the photoaffinity reagent [125I]cyanopindolol-diazirine selectively labels a 62 kDa protein in IBAT plasma membranes that displays pharmacological properties of a beta 1-adrenergic subtype. Relatively high concentrations of BRL 37344 (10 microM) are required to displace [125I]cyanopindolol-diazirine binding to the 62 kDa protein. Taken together, the results suggest that two different populations of beta-adrenergic receptors may co-exist in BAT plasma membranes: a small population (about 15%) of atypical beta-receptors and a large population of beta 1-receptors that exhibit high and low affinities for BRL 37344, respectively. PMID- 2902860 TI - Persistent beta-adrenoceptor blockade with alkylating pindolol (BIM) in guinea pig left atria and trachea. AB - The actions of alkylating pindolol (N8-bromoacetyl-N1-3'-(4-indolyloxy)-2' hydroxypropyl[z]-1,8- diamino-p-menthane; BIM) have been examined on beta adrenoceptors in guinea-pig left atria and trachea. In organ bath experiments, addition of BIM (greater than or equal to 0.1 microM), followed by washout, produced concentration-dependent rightward shifts of the dose-response curve to cumulative additions of (-)-isoprenaline and oxymethylene-isoprenaline and reductions in the maximal response. The "apparent" pA2 value for BIM was 9.23 +/- 0.20 (slope = 0.98 +/- 0.20). Changes in the maximal density of beta-adrenoceptor binding sites were determined in guinea-pig left atrial membranes using [125I] cyanopindolol. BIM (0.1, 1.0 and 10 microM) produced 14, 23 and 41% reductions in Bmax with no change in KD. The binding of [125I]-BIM to guinea-pig left atrial membranes had a high non-specific binding component and a pseudo-Hill coefficient less than unity. The "apparent" KD value of [125I]-BIM at beta-adrenoceptor binding sites was 85.7 +/- 57.9 pM. PMID- 2902859 TI - Influence of cold exposure on liver amino acid metabolism enzymes of the rat. AB - The activities of alanine, aspartate and branched-chain amino acid transaminases, glutamate dehydrogenase, glutamine synthetase and adenylate deaminase have been studied in liver of male rats exposed [12 hours at 4 degrees C] or acclimated [15 days at 4 degrees C] to cold temperature. Cold temperature induced an increase of the activities of glutamate dehydrogenase and alanine and aspartate transaminases both in cold-exposed and cold-acclimated animals; adenylate deaminase activity diminished after 15-day cold acclimation. There were not significant changes induced by cold temperature in the activities of the other two enzymes studied. These results agree with a possible direct implication of amino acid utilization by the liver in the context of the overall thermogenic response to cold temperature. PMID- 2902861 TI - Pharmacological profile of a new potent 5-hydroxytryptamine (5-HT2) alpha 1 receptor antagonist. AB - In in vitro binding studies ZK 33.839 (4-(3-[3-(4-(4-fluorobenzoyl)-1 piperidinyl)-propoxy]-4-methoxyphenyl)- 2-pyrrolidone) showed highly specific binding affinity for 5-hydroxytryptamine (5-HT2) and alpha 1-receptors. With 2.0 nmol/l and 5.2 nmol/l both Ki-values occur in the same concentration range. The pharmacodynamic profile of ZK 33.839 has been investigated under in vitro and in vivo conditions. In human platelets, in rat vascular smooth muscle and in guinea pig tracheal smooth muscle 5-HT-induced proaggregatory and contractile effects were inhibited dose-dependently with IC50-values ranging from 1.85 x 10(-8) mol/l to 9 x 10(-9) mol/l. 5-HT-induced amplification of the response of rabbit femoral artery to different vasoconstrictors (angiotensin II, histamine, norepinephrine, and prostaglandin F2 alpha) and 5-HT-mediated increase of microvascular permeability in hamster cheek pouch preparation were also inhibited by ZK 33.839. ZK 33.839 was found to be a potent alpha 1-receptor antagonist, the pA2-value in rat aortic strips determined against phenylephrine was 9.16. In blood-perfused hindquarters of anaesthetized rats, pretreated with reserpine, pressor dose response curves to norepinephrine and 5-HT were shifted to a higher dose range. ZK 33.839 lowered blood pressure in conscious Dahl-S-rats and in anaesthetized rabbits. Decrease of blood pressure was due to a decrease of peripheral vascular resistance. Cardiac output and heart rate were not significantly altered. ZK 33.839 is a potential antihypertensive compound which combines vasodilatatory effects due to selective alpha 1-receptor antagonistic action and platelet antiaggregatory, antivasospastic, and vasoprotective properties due to selective 5-HT2-receptor blockade. PMID- 2902862 TI - [Asthma and beta-blocker eye drops (timolol, metipranolol, carteolol). Inhibition of chronotropic effects of isoprenaline]. AB - Effects of three beta antagonist eye drops are studied in three parallel groups of asthmatic patients. Each ocular topic lowers FEV1 with a maximal effect of 13.4 +/- 2.1% for timolol (n = 15), -17.9 +/- 3.3% for metipranolol (n = 10), and -8.6 +/- 3.0% for carteolol (n = 10). Vital capacity, systolic and diastolic pressure scarcely change, but all three eye drops give a dose dependent sinus bradycardia. Intravenous infusion of isoproterenol (exclusive beta agonist) shows an important inhibition of cardiac receptors by timolol. Doses necessary to increase heart rate of 50% are of 0.242 +/- 0.019 microgram/kg before eye drops are instilled and of 0.647 +/- 0.054 microgram/kg after timolol treatment. This study stresses out the necessity of following recommended doses and respecting carefully classical contra indications of beta blocking agents and specially asthma. PMID- 2902863 TI - A prospective study of HIV-2 prevalence in France. AB - A seroepidemiological surveillance study to investigate the spread of HIV-2 infection in France was organized in the last semester of 1987 on 100 114 blood donors and 10 004 selected people. Sera were simultaneously tested for antibodies to HIV-1 and to HIV-2 by enzyme-linked immunosorbent assay (ELISA) and were confirmed by specific Western blot. A spot test using synthetic peptides was also applied when a sample was reactive by ELISA HIV-1 and HIV-2 and was confirmed as HIV-1 by Western blot. A total of 30 blood donors were confirmed as HIV-1 positive (0.030%) and no sample was confirmed as HIV-2 positive. In the selected population, the prevalence of HIV-infected people was 7.1% for HIV-1 and 0.09% for HIV-2. Eight of the nine HIV-2 cases were directly or indirectly connected to West Africa. Only one HIV-2 case had no known contact with these countries; he has been transfused and is under investigation. Except for this possible HIV-2 infection in a blood recipient, no HIV-2 seropositivity was found in at-risk groups (homosexuals, drug addicts and haemophiliacs). At present, HIV-2 does not seem to be widely spread in France. Seroepidemiological surveillance will be continued. PMID- 2902864 TI - Follow-up of subjects with isolated and persistent anti-core (anti-p24 or anti p17) antibodies to HIV. AB - Systematic screening of blood donations by enzyme-linked immunosorbent assay (ELISA) for HIV antibodies carries a false-positive rate: the sera involved react in Western blot to core antigens (p24 or p17) but reactivity to envelope is absent. We studied 22 subjects with persistent and isolated anti-core reactivities; 75 HIV seropositive patients were controls. The epidemiological data and the follow-up and biological tests performed in these two populations argue that donors with persistent and isolated anti-core antibodies are not seroconverting for HIV. We conclude: (1) that verification of all anti-HIV ELISA positive sera by Western blot is essential and that the presence of at least once anti-envelope (gp120 or gp41) antibody is indispensable for the diagnosis of HIV infection; (2) that the solitary anti-p24 or anti-p17 bands observed on Western blot are false-positive. There is no evidence that donors with such reactivities are HIV-infected. PMID- 2902865 TI - Impaired T-lymphocyte-dependent immune responses to microbial antigens in patients with HIV-1-associated persistent generalized lymphadenopathy. AB - T-cell mediated and humoral responses directed to microbial antigens were investigated, at the time of the initial visit, in a group of 139 patients with HIV-1-related persistent generalized lymphadenopathy (PGL) enrolled in a longitudinal study. In vivo and in vitro cell-mediated responses to tuberculin were lower in patients than in controls. Differences were not significant for candidin and streptococcal antigen in vitro, whereas higher responses were observed in the patient group for cytomegalovirus antigen. Following immunization, a subgroup of patients did not have a significantly raised serum antitetanus antibody level, whereas in vitro lymphocyte proliferative responses to tetanus toxoid were lower than in controls. No association was found between these abnormalities and other immunological parameters, including the blood level of CD4+ lymphocytes. Lower responses to most microbial antigens were observed in patients with HIV-1-related symptoms in addition to lymphadenopathy, or the patients who progressed to AIDS in the 2 years following the study. Moreover, intravenous drug users showed higher responses than homosexual patients, possibly because of the influence of previous infections on immunological responses to microbial antigens. PMID- 2902866 TI - Synthesis and hydrolysis of ATP by the mitochondrial ATP synthase. AB - A brief summary of the factors that control synthesis and hydrolysis of ATP by the mitochondrial H+-ATP synthase is made. Particular emphasis is placed on the role of the natural ATPase inhibitor protein. It is clear from the existing data obtained with a number of agents that there is no correlation between variations of the rate of ATP hydrolysis and ATP synthesis as driven by respiration. The mechanism by which each condition differentially affects the two activities is not entirely known. For the case of the natural ATPase inhibitor protein, it appears that the protein controls the kinetics of the enzyme. This control seems essential for achieving maximal accumulation of ATP during electron transport in systems that contain relatively high concentrations of ATP. PMID- 2902867 TI - Carrier detection in X-pigmentary retinal dystrophy (X-linked retinitis pigmentosa) by DNA restriction fragment length polymorphism studies. AB - As part of a patient care and DNA research programme commenced in 1985, a number of DNA markers on the short arm of the X chromosome have been used to demonstrate restriction fragment length polymorphisms (RFLPs) segregating with the X pigmentary retinal dystrophy (X-linked retinitis pigmentosa) gene. The analysis of the segregation of the RFLPs in 3 kindreds enables carrier detection, to a high degree of probability, in females at risk who are not manifesting symptoms and signs. PMID- 2902869 TI - Adherence of Fusobacterium necrophorum biovar A and B strains to erythrocytes and tissue culture cells. AB - Fusobacterium necrophorum biovar A and biovar B were examined for haemagglutinability and ability to adhere to cells. Six biovar A strains agglutinated tannic-acid-treated chicken erythrocytes (1/32-1/64), as well as untreated chicken erythrocytes (1/16-1/64). They adhered well to MDBK and FL cells. Haemagglutination by them was not inhibited with D-mannose. In six biovar B strains, the haemagglutination titre was low for chicken erythrocytes and showed no increase for tannic-acid-treated chicken erythrocytes. These strains exhibited a weak ability to adhere to MDBK and FL cells. PMID- 2902870 TI - [Epileptic seizure model utilizing additive effects of excitatory amino acids]. AB - L-glutamate (GLU) and L-aspartate (ASP), major excitatory amino acids in the brain, are believed to have an important role in the generalization and expression of epileptic seizures. Their analogues such as kainate, folate, ibotenate and quisqualate have been widely used to produce epileptic seizures, since they have a potent excitatory action. However, these analogues produce striking neuronal damage at the injection site when injected intracerebrally. Therefore, these analogues are not appropriate for studying the mechanisms of epilepsy, which is believed to be based on the functional changes of the brain. On the other hand, although GLU and ASP themselves have minimal neurotoxic action, a relatively higher dosage than that of their analogues is needed to produce epileptic seizures. A recent report, in which Freeman has found that combined GLU/ASP released from the lobster neuromuscular synapse in a molar ratio of 1:3 (GLU/ASP) produces strong excitation, may provide some clue to this problem. In this study, we examined the features of epileptic seizures and neuronal damage following the injection of GLU/ASP combined in this molar ratio into the amygdala (AM) of rats. Twenty-nine adult male Wistar rats weighing 200 250 g were used. All animals had received a cannula made of a 22-G stainless steel tube into the left AM. A bipolar recording electrode made of stainless steel wire was attached to its wall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902868 TI - Production, purification and partial characterization of a new adhesive factor (F42) produced by enterotoxigenic Escherichia coli isolated from pigs. AB - Production of the F42 adhesive factor by porcine enterotoxigenic Escherichia coli (ETEC) grown on minimal solid medium was glucose-dependent. The addition of alanine and sodium acetate to this medium repressed the expression of this antigen whose production was also inhibited when the pH of the growing medium was lower than 7.4. The antigen was extracted from F42-positive ETEC grown in minimal liquid medium supplemented with 0.5% glucose. The cells were suspended in buffered 1 M NaCl and heated at 60 degrees C. The supernatant was then treated with ammonium sulphate and the resulting precipitate treated with deoxycholate followed by chromatography of the deoxycholate-soluble material on Sepharose-4B. The molecular weight of F42 purified antigen was near 31,000 daltons and its pI 3.2, as determined by polyacrylamide gel electrophoresis and isoelectric focusing, respectively. Immunoelectrophoretic studies showed that the purified F42 antigen presented a slight anodic migration and was recognized only by its homologous antiserum. PMID- 2902871 TI - Comparison of neuromuscular blockade in the diaphragm and the hand. AB - Neuromuscular blockade was recorded in the diaphragm and in the adductor pollicis muscle using unilateral supramaximal stimulation of phrenic and ulnar nerves and measurement of the mechanical effect of each. After administration of atracurium 0.4-0.5 mg kg-1 to 10 patients, both onset and recovery of neuromuscular blockade in the diaphragm occurred before that in adductor pollicis and there was a linear relationship between recovery in diaphragm and adductor pollicis. After administration of vecuronium 0.08-0.1 mg kg-1 to a further 10 patients, paralysis occurred in the diaphragm before adductor pollicis in all except one patient, in whom it occurred simultaneously. Reappearance of adductor pollicis twitch occurred in six patients after all four twitches had returned in the diaphragm, but the rate of recovery of twitch height in the diaphragm was more rapid than in adductor pollicis in every patient. PMID- 2902872 TI - Potency of atracurium and vecuronium at the diaphragm and the adductor pollicis muscle. AB - Train-of-four stimulation was applied to the ulnar and phrenic nerves in 18 adult patients anaesthetized with nitrous oxide and halothane in oxygen. The response of the adductor pollicis and the diaphragm were measured. Incremental doses of atracurium and vecuronium were given, with an infusion to replace drug lost by elimination or distribution. The mean (SEM) doses of atracurium associated with 50% and 90% depression of response to the first stimulation in the train-of-four (ED50 and ED90) were 90 (9) and 133 (10) micrograms kg-1 at the adductor pollicis, and 130 (9) and 245 (17) micrograms kg-1 at the diaphragm, respectively. The mean (SEM) ED50 and ED90 of vecuronium were 25 (2) and 38 (4) micrograms kg-1 at the adductor pollicis and 34 (3) and 58 (5) micrograms kg-1 at the diaphragm, respectively. The mean (SEM) ED50 ratios were 1.56 (0.16) for atracurium and 1.47 (0.16) for vecuronium. ED90 ratios were 1.93 (0.29) and 1.55 (0.17) for atracurium and vecuronium, respectively. It is concluded that both atracurium and vecuronium exhibit a similar degree of sparing of the diaphragm. PMID- 2902874 TI - Pharmacokinetics and dynamics of famotidine in patients with renal failure. AB - 1. Famotidine, a new histamine H2-receptor antagonist was administered intravenously (20 mg) to 22 patients with end stage renal disease during a dialysis free interval (n = 6) and during different blood purification processes including haemodialysis (HD; n = 4), intermittent haemofiltration (HF; n = 4), continuous haemofiltration (CHF; n = 4) and continuous ambulatory peritoneal dialysis (CAPD; n = 4). The plasma, the dialysate/filtrate and the urine concentrations of famotidine were analysed by h.p.l.c. 2. In addition, intra gastric pH was measured by a long-term-pH probe in seven patients with renal failure and in six patients with normal renal function (control group) following 20 mg famotidine. 3. A 7 to 10 fold prolongation of famotidine's elimination half life (27.2 +/- 8.5 h; mean +/- s.d.) was observed in patients with renal failure as compared with the half-life (2.6-3.6 h) in subjects with normal renal function. 4. Total body clearance (CL) and volume of distribution (V) were found to be 33.5 +/- 10.1 ml min-1 and 1.3 +/- 0.7 l kg-1, respectively in patients with end-stage renal failure. 5. Blood purification processes have shown considerable variation in clearing famotidine from the body: 16.4 +/- 8.9 and 6.0 +/- 2.9% of the administered dose in HD with polysulphone and cuprophan membranes respectively, 7.7 +/- 5.2% in HF with a polyacrylonitrile membrane (each for 5 h), 4.5 +/- 1.1% in CAPD and 16.2 +/- 4.9% in CHF with a polysulphone membrane within 24 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902873 TI - Comparative effects of bisoprolol and acebutolol in smokers with airway obstruction. AB - 1. The effects of single oral doses of 10 mg bisoprolol and 400 mg acebutolol on respiratory function were studied in nine smokers with airway obstruction in a double-blind, placebo-controlled experiment. 2. The effects of the drugs were assessed by measuring specific airway conductance (sGaw) for 3 h after their administration and by studying their interaction with the bronchodilator response to inhaled salbutamol. 3. sGaw did not change for 3 h after bisoprolol or acebutolol administration. The bronchodilator response to inhaled salbutamol was not affected by bisoprolol but significantly reduced by acebutolol (P less than 0.05 vs placebo). 4. Under these conditions, bisoprolol behaves like a selective beta 1-adrenoceptor antagonist but acebutolol exhibits less beta 1-adrenoceptor selectivity. PMID- 2902875 TI - Maternal hormone levels in early gestation of cryptorchid males: a case-control study. AB - A case-control study was conducted to assess maternal hormonal factors associated with increased risk of bearing a cryptorchid son. Serum samples were collected during the first trimester of pregnancy from participants in the US Collaborative Perinatal Study. Twenty-five mothers of normal offspring (controls) were individually matched on medical center, age, parity, weight and length of gestation at the time of sampling to women bearing sons who had a diagnosis of cryptorchidism at one year of age or older. Compared with controls, mothers of cryptorchid sons (cases) had significantly greater percentages of non-protein bound (P = 0.010) and albumin-bound (P = 0.014) estradiol during the first trimester of the index pregnancy. On average, cases had 16% more bioavailable oestradiol than controls. Levels of human chorionic gonadotropin, testosterone, non-protein bound testosterone and sex-hormone binding globulin did not differ between the two groups. The data presented support the hypothesis that cryptorchidism results from elevated maternal oestrogen levels early in pregnancy. PMID- 2902876 TI - Carrier detection in 50 haemophilia A kindred by means of three intragenic and two extragenic restriction fragment length polymorphisms. AB - Carrier detection was attempted in 50 haemophilia A kindred by means of restriction fragment length polymorphism (RFLP) analysis using two linked and three intragenic probes. The sample comprised 330 individuals including 70 haemophiliacs, 45 obligate carriers and 100 possible carriers. Non-related haplotypes contained within the sample group were used to tabulate the intragenic RFLP allele frequencies. The linkage disequilibrium existing between the XbaI and Bc1I RFLP was shown to be less than previously reported, such that 69% of women are informative for at least one of these two polymorphisms. 36 women were subsequently diagnosed as carriers and 37 as being normal: in 52 of these, diagnosis was based either on intragenic RFLPs or linked RFLP plus strong phenotypic data, and was considered to be unequivocal; in the remaining 21, diagnosis was based on linked RFLPs alone and was considered to be probabilistic, with a 5-10% possible error rate. 27 of the possible carriers, either from families with sporadic haemophilia or from families where missing members precluded haplotype analysis, remained unassigned. 72% of the obligate carriers and firmly diagnosed carriers were heterozygous and phase known for at least one intragenic RFLP, whereas 6% were uninformative for the RFLPs for which they were examined. In 54 informative meioses, three recombinations between the factor VIII locus and the DX13 and/or ST14 loci were observed, giving a recombination rate of 5.5%. 15 prenatal diagnoses were carried out. Of the 11 male fetuses, six were shown to be affected and five to be normal. In three of four prenatal diagnoses where only a linked RFLP was informative, the result was confirmed by fetoscopy, fetal blood sampling, and factor VIII assay. PMID- 2902877 TI - Comparative studies of the sugar chains of aminopeptidase N and dipeptidylpeptidase IV purified from rat kidney brush-border membrane. AB - Asparagine-linked sugar chains of rat kidney aminopeptidase N and dipeptidylpeptidase IV were investigated comparatively. Oligosaccharides released from the two enzymes by hydrazinolysis were fractionated by paper electrophoresis, serial chromatographies on columns of immobilized Aleuria aurantia lectin, concanavalin A, phytohemagglutinin E4, and Datura stramonium agglutinin, and Bio-Gel P-4 (less than 400 mesh) column chromatography. Structures of oligosaccharides in each fraction were assumed by their effective molecular sizes and behaviors on the four lectin columns and then confirmed by sequential exoglycosidase digestion and methylation analysis. The sugar chains of aminopeptidase N and dipeptidylpeptidase IV are almost the same as those of rat kidney gamma-glutamyltranspeptidase reported previously [Yamashita, K., Hitoi, A., Matsuda, Y., Tsuji, A., Katunuma, N., & Kobata, A. (1983) J. Biol. Chem. 258, 1098-1107]. They are a mixture of 5 high mannose type sugar chains and 32 (for aminopeptidase N) or 26 (for dipeptidylpeptidase IV) mono-, bi-, tri-, and tetraantennary complex type sugar chains. The unique feature of the complex-type sugar chains of both enzymes is that they all contain the bisecting N acetylglucosamine residue and are incompletely galactosylated in their outer chain moieties. PMID- 2902878 TI - Oxidation of malate by the mitochondrial succinate-ubiquinone reductase. AB - The purified succinate-ubiquinone reductase catalyzes the L- (or D-) malate: acceptor oxidoreductase reaction with Km for malate of about 2.10(-3) M and initial Vmax of 50 and 100 nmol per min per mg of protein for L- and D stereoisomers, respectively (25 degrees C, pH 7.0). The reaction rate rapidly decreases both in the absence and presence of L-glutamate and L-glutamate oxaloacetate transaminase added for trapping of oxaloacetate. Both keto and enol forms of oxaloacetate were found to be strong, slowly dissociating inhibitors of succinate dehydrogenase; the first-order rate constant for the enzyme inhibition by the enol form is about 3 times as high as that by the keto form. Oxidation of malate by succinate dehydrogenase in the presence of the oxaloacetate trapping system occurs at an indefinitely constant rate when enoloxaloacetate, which is an immediate product of the reaction, is rapidly converted into the keto isomer--a substrate for transaminase. A quantitative kinetic scheme for malate oxidation by succinate dehydrogenase which includes two kinetically distinct enzyme oxaloacetate complexes is proposed, and the specific role of the mitochondrial oxaloacetate keto-enol-tautomerase (EC 5.3.2.2) in the regulation of succinate dehydrogenase is suggested. PMID- 2902879 TI - Subcellular distribution of malate-aspartate cycle intermediates during normoxia and anoxia in the heart. AB - The subcellular distribution of adenine nucleotides, phosphocreatine and intermediates of the malate-aspartate cycle was investigated in adult rat heart myocytes under normoxia and anoxia. Cytosolic and mitochondrial concentrations of metabolites were determined by a fractionation method using digitonin. Under normoxia, cytosolic/mitochondrial gradients were found for ATP (c/m = 4), AMP (c/m less than 0.01), citrate (c/m = 0.5), aspartate (c/m = 3), glutamate (c/m = 2), while phosphocreatine and glutamine were confined to the cytosolic space. No gradients were found for malate and 2-oxoglutarate. The results show that the transport of electrons from the cytosol into the mitochondria is supported by the glutamate gradient and by a high glutamate/aspartate ratio inside the mitochondria (Glu/Asp = 15) which is maintained by the energy-dependent Glu-Asp exchange across the mitochondrial membrane. Under anoxia, cytosolic glutamate is transaminated with pyruvate, yielding alanine and 2-oxoglutarate, which is oxidized to succinate inside the mitochondria and leaves the cell. The data indicate that stimulation of transamination is caused by a mass action effect following a decrease in cytosolic 2-oxoglutarate which may be due to succinate-2 oxoglutarate exchange across the mitochondrial membrane. Inhibition of the energy dependent inward transport of glutamate may support this process. PMID- 2902880 TI - Catecholamine stimulation of ion transport in the toad urinary bladder. AB - We have observed that serosal catecholamines increase the amplitude of the short circuit current (Isc) in the toad urinary bladder by as much as 450%. Chemical sympathectomy with 10(-6) M 6-hydroxydopamine and the sympathomimetic effects of 10(-5) M tyramine indicate a reservoir of amines in the serosal stroma of the tissue. The urinary epithelium from the toad responds to six adrenoceptor agonists: (-)-epinephrine, (-)-norepinephrine, (-)-phenylephrine, clonidine, methoxamine and oxymetazoline. The alpha 2-adrenoceptor agonist clonidine is most potent for stimulating Isc. Some agonists were found to diminish Isc. Apparently this is related to a simultaneous increase in the transepithelial flux of both chloride and sodium. The Isc response to the catecholamines is also inhibited by several adrenoceptor antagonists. The alpha 2-adrenoceptor antagonist yohimbine is more effective than the alpha 1-antagonist prazosin for blocking the stimulation of epithelial transport. As a result of these studies, we have tentatively classified the serosal adrenoceptor of the toad urinary bladder as alpha 2. PMID- 2902881 TI - Inhibition of activity and quenching of intrinsic fluorescence of transglutaminase by acrylamide are independent events. AB - Addition of low concentrations of acrylamide to the assay mixture of erythrocyte transglutaminase leads to a strong inhibition of the enzyme with a mechanism consistent with a non-competitive inhibition against both substrates. For the quenching of the intrinsic fluorescence of the protein, much higher concentrations of acrylamide are required so that both phenomena appear independent of each other. In this particular case, therefore, acrylamide can be employed to obtain information on ligand-triggered conformational changes. PMID- 2902882 TI - Inhibition of prostaglandin E1-induced activation of adenylate cyclase in human blood platelet membrane. AB - Activation of human blood platelet adenylate cyclase is initiated through the binding of prostaglandin E1 to the membrane receptors. Incubation of platelet membrane with [3H]prostaglandin E1 at pH 7.5 in the presence of 5 mM MgCl2 showed that the binding of the autacoid was rapid, reversible and highly specific. The binding was linearly proportional to the activation of adenylate cyclase. Although the membrane-bound radioligand could not be removed either by GTP or its stable analogue 5'-guanylylimido diphosphate, 150 nM cyclic AMP displaced about 40% of the bound agonist from the membrane. Scatchard analyses of the binding of the prostanoid to the membrane in the presence or absence of cyclic AMP showed that the nucleotide specifically inhibited the high-affinity binding sites without affecting the low-affinity binding sites. Incubation of the membrane with 150 mM cyclic AMP and varying amounts of prostaglandin E1 (25 nM to 1.0 microM) showed that the percent removal of the membrane-bound autacoid was similar to the percent inhibition of adenylate cyclase at each concentration of the agonist. At a concentration of 25 nM prostaglandin E1, both the binding of the agonist and the activity of adenylate cyclase were maximally inhibited by 40%. With the increase of the agonist concentration in the assay mixture, the inhibitory effects of the nucleotide gradually decreased and at a concentration of 1.0 microM prostaglandin E1 the effect of the nucleotide became negligible. These results show that cyclic AMP inhibits the activation of adenylate cyclase by low concentrations of prostaglandin E1 through the inhibition of the binding of the agonist to high-affinity binding sites. PMID- 2902883 TI - The effects of prostanoids on estrogen-dominated rat myometrial longitudinal muscle in vitro. AB - The purpose of these experiments was to characterize the contractile response of longitudinal muscle from the estrogen-dominated rat uterus to natural and synthetic prostanoids. The biological significance is 1) to provide evidence for or against a physiological role for each natural prostanoid in the regulation of myometrial activity, 2) to determine if each prostanoid has pharmacological potential for the manipulation of myometrial activity, and 3) to understand the structural requirements for prostanoid action on the myometrium. All analogs tested produced excitation of the myometrium in vitro through what appeared to be a direct action on the muscle. The order of potency of the natural prostanoids was prostaglandin (PG) F2 alpha = PGD2 = PGE2 = PGE1 greater than PGA2 = PGB2 = 6 keto-PGF1 alpha. This order of potency was not consistent with any single currently recognized prostanoid receptor. Furthermore, PGF2 alpha had an EC50 (effective concentration that produces 50% of the maximal response) of 0.5 microM, which was low in comparison to other PGF2 alpha-sensitive tissues. There were large differences in the maximum tension developed in response to the prostanoids tested, only PGF2 alpha, PGE2 and 6-keto PGF1 alpha were full agonists. Although the simplest explanation of these data was that the rat uterus contains a single novel type of prostanoid receptor, the existence of multiple receptor subtypes could not be disproved. Evidence from the effect of synthetic analogs suggested that neither thromboxane A2 nor PGI2 are physiological regulators of activity in this tissue. PMID- 2902884 TI - Contrast in levels of metabolic enzymes in human and mouse ova. AB - A methodology is described for analyzing single human ova for 8 or 9 different metabolic enzymes, or 4 or 5 enzymes plus as many metabolites. This overcomes an obstacle to the study of human ovum metabolism: the severe limitation of usable material. Results obtained with this methodology, applied to discarded specimens from an in vitro fertilization program, indicate that in spite of imperfections these ova can provide a valid picture of the metabolic characteristics of normal human ova. Data are presented for 17 enzymes from 8 metabolic pathways in human and mouse ova. Relative to size, 10 of the enzymes were substantially higher in human than mouse ova. Most dramatically so were 2 enzymes of fatty acid metabolism (10-fold and 15-fold), hexokinase (9-fold), and aspartate aminotransferase (19-fold). This suggests that major species differences in metabolism are present. The validity of the human data, in spite of restriction to discarded material, is supported by (1) consistency of results among most of the ova, 2] concordance between average levels with those of rare specimens that were discarded because sperm were not available, and (3) the presence of adenosine triphosphate (ATP) concentrations similar to those of normal mouse ova. Surprisingly, both human and mouse ova contain phosphocreatine at levels nearly equal of those of ATP. PMID- 2902885 TI - Causes of retinopathy of prematurity: an epidemiologic perspective. AB - This chapter presents a strategy for integration of the current thinking about the causes of ROP. Application of these concepts assumes that results of any etiologic study are derived from valid methods. Discussion of principles of validity in epidemiologic studies is beyond the scope of this paper. However, reference was made to two sources of invalidity in studies of the causes of ROP: 1) the empirical or operational definition and measurement of the conceptual cause, and 2) confounding by degree of immaturity of retinal vasculatures, particularly with regard to interpretation of duration of ventilatory support as a cause of ROP. The distinction was made between an agent that initiates or promotes disease mechanism and a cause. Failure to appreciate this distinction has contributed to the confusion about the role of oxygen in the pathogenesis of retinopathy. Apart from settings of oxygen mismanagement, oxygen per se is part of the mechanism for development of disease. Certainly there are other biochemical requirements in addition to oxygen that set the stage for full-blown disease. Factors that are associated with the disruption of normal development of retinal vasculature and are susceptible to manipulation (either by reduction or elimination) during the prenatal and postnatal period may be more useful component causes to investigate. PMID- 2902886 TI - Defective T suppressor-inducer cell function in human immune deficiency virus seropositive hemophilia patients. AB - In human immune deficiency virus (HIV)-seropositive hemophilia patients, a low number of CD4 + lymphocytes is found, as well as a low CD4+/CD8+ ratio. In previous studies, it has been shown that antigen-specific T-helper cell (CD4+) function was present and no excessive antigen-specific T-suppressor cell (CD8+) function could be demonstrated. In this report, we studied another activity of CD4+ cells, namely the capacity to induce T-suppressor cell activity. The results clearly show a selective dysfunction of CD4+ suppressor-inducer (Tsi) cell function. Since these HIV-seropositive hemophilia patients showed the presence of activated B cells in the peripheral circulation refractory to antigen-specific T helper cell signals and secreting specific antibodies spontaneously, we raised the hypothesis that the activated B cells in the patients activate the Tsi cells in vivo. This constant activation leads to a functional exhaustion of the Tsi cell pool. PMID- 2902887 TI - Diagnostic role of an immunoassay-detected polymorphism of factor IX for potential carriers of hemophilia B. AB - In hemophilia B, assays based on a monoclonal antifactor IX specific for the Thr 148 variant of an exonic polymorphism have diagnosed carriers in selected families by either establishing linkage or by indicating the presence or absence of a given normal factor IX. The sensitivity of the immunoassays for detecting heterozygous women was explored by comparing results from immunoassays with solid phase polyclonal v the monoclonal antifactor IXs. Factor IX with the normal Ala 148 variant gave a flat dilution curve, qualitatively distinct from factor IX with the Thr-148 variant in the monoclonal assay. The two were indistinguishable in the polyclonal assay. Mixtures of equal amounts of the two types gave an intermediate result, about half as reactive in the monoclonal as compared with the polyclonal assay system. Whereas mixtures with 10% Ala-148 and 90% Thr-148 factor IXs could not readily be distinguished from Thr-148 factor IX plasma, as little as 1% of the Thr-148 protein was detected in Ala-148 factor IX plasma. The frequency of the Ala-148 variant varied in individuals with different ethnic backgrounds; it was found in 29% of white, 12% of black, and none of Asian blood donors' factor IX genes in Seattle. Only 4% of samples from South African black men were nonreactive (ie, Ala-148). The Thr/Ala-148 dimorphism is in strong linkage disequilibrium with Taql restriction fragment length polymorphisms (RFLPs). Three recombinations were noted in normal white genes and one in a normal black factor IX gene (less than 2% of those examined). In 34 white families with at least one woman being a possible carrier, genetically, the immunoassay results were informative in 18. RFLP analyses were informative in eight of the 15 families tested. In five families each, assignment of carrier status was made to a woman by only DNA or only immunoassay results, whereas the other approach was noninformative. The immunoassays provide a rapid, inexpensive screening test and complement DNA analysis in white women who are potential carriers of hemophilia B. PMID- 2902888 TI - Toxicity of sodium dichloro S-triazinetrione to Drosophila melanogaster. PMID- 2902889 TI - Outcome of untreated infection with Entamoeba histolytica in homosexual men with and without HIV antibody. AB - Among homosexual men the prevalence of infection with Entamoeba histolytica is high. To determine the clinical importance of this infection 55 homosexual men carrying the parasite were investigated in detail. No clinical, serological, or histological evidence of invasive amoebiasis was found in any of them. The patients were not treated and were followed up for 12 to 29 months (mean 21.6 months), during which period none developed symptoms that could be attributed to E histolytica. Spontaneous loss of the parasite occurred in 17 patients, some of whom later became reinfected. Sixteen patients had antibody to human immunodeficiency virus, and infection with E histolytica showed the same benign course in them as in the patients who did not have antibody. Throughout the study classification of the isolates of E histolytica consistently showed that they belonged only to non-pathogenic zymodemes. The findings provide further evidence that E histolytica in homosexual men is a commensal organism. PMID- 2902890 TI - Beta-adrenoceptor stimulation enhances transmitter output from the rat phrenic nerve. AB - 1. Neurally-evoked output of newly synthesized [3H]-acetylcholine from the rat phrenic nerve was measured in the absence of cholinesterase inhibitors. 2. Noradrenaline and isoprenaline enhanced neurally-evoked transmitter output markedly. Moreover, immediately after the application of noradrenaline the basal tritium efflux increased significantly. 3. Pretreatment with propranolol (0.1 mumol l-1) or atenolol (0.3 mumol l-1) completely prevented the stimulatory effect of noradrenaline and isoprenaline on evoked transmitter output. 4. The facilitatory effect of isoprenaline declined, when the exposure time was increased. This observation supports the assumption that beta-adrenoceptors can be desensitized or inactivated during continued exposure to agonists. 5. It was shown for the first time that stimulation of beta-adrenoceptors enhances transmitter output from the motor nerve. It is proposed that these beta adrenoceptors are of the beta 1-subtype and are localized on the endings of motor nerves. Circulating catecholamines may facilitate neuromuscular transmission by stimulation of presynaptic beta-adrenoceptors. PMID- 2902891 TI - Selective regulation of beta 1- and beta 2-adrenoceptors in the human heart by chronic beta-adrenoceptor antagonist treatment. AB - 1. In 44 patients undergoing coronary artery bypass grafting, the effect of chronic administration of the beta-adrenoceptor antagonists sotalol, propranolol, pindolol, metoprolol and atenolol on beta-adrenoceptor density in right atria (containing 70% beta 1- and 30% beta 2-adrenoceptors) and in lymphocytes (having only beta 2-adrenoceptors) was studied. 2. beta-Adrenoceptor density in right atrial membranes and in intact lymphocytes was assessed by (-)-[125I] iodocyanopindolol (ICYP) binding; the relative amount of right atrial beta 1- and beta 2-adrenoceptors was determined by inhibition of ICYP binding by the selective beta 2-adrenoceptor antagonist ICI 118,551 and analysis of the resulting competition curves by the iterative curve fitting programme LIGAND. 3. With the exception of pindolol, all beta-adrenoceptor antagonists increased right atrial beta-adrenoceptor density compared to that observed in atria from patients not treated with beta-adrenoceptor antagonists. 4. All beta-adrenoceptor antagonists increased right atrial beta 1-adrenoceptor density; on the other hand, only sotalol and propranolol also increased right atrial beta 2 adrenoceptor density, whereas metoprolol and atenolol did not affect it and pindolol decreased it. 5. Similarly, in corresponding lymphocytes, only sotalol or propranolol increased beta 2-adrenoceptor density, while metoprolol and atenolol did not affect it and pindolol decreased it. 6. It is concluded that beta-adrenoceptor antagonists subtype-selectively regulate cardiac and lymphocyte beta-adrenoceptor subtypes. The selective increase in cardiac beta 1-adrenoceptor density evoked by metoprolol and atenolol may be one of the reasons for the beneficial effects observed in patients with end-stage congestive cardiomyopathy following intermittent treatment with low doses of selective beta 1-adrenoceptor antagonists. PMID- 2902892 TI - Peripheral sympatho-inhibitory cardiovascular effects of opioid peptides in anaesthetized rabbits. AB - 1. Opioid agonists influence isolated cardiovascular tissues from rabbits, as well as the cardiovascular system of pithed rabbits, through presynaptic receptors on postganglionic sympathetic nerve fibres. The present experiments were carried out in order to study effects which result from activation of these receptors in anaesthetized rabbits. 2. In pithed rabbits with electrically stimulated sympathetic outflow, infusion of [D-Ala2-D-Leu5]-enkephalin (DADLE) 10 micrograms kg-1 min-1 and dynorphin-(1-13) (dynorphin) 1 microgram kg-1 min-1 decreased the plasma noradrenaline concentration, mean arterial pressure (MAP) and heart rate. The effects of dynorphin and, less completely, those of DADLE were antagonized by the peripherally selective opioid antagonists N-methyl naloxone bromide (NMN) 1.3 mg kg-1 and N-methyl levallorphan methanesulphonate (NML) 1-3 mg kg-1. 3. In pentobarbitone-anaesthetized rabbits, DADLE 3-30 micrograms kg-1 min-1 and dynorphin 0.3-3 micrograms kg-1 min-1 decreased the plasma noradrenaline concentration and MAP. The highest dose of dynorphin also decreased heart rate, whereas DADLE 10 micrograms kg-1 min-1 caused slight cardioacceleration. The effects of DADLE but not those of dynorphin decreased upon repeated administration. 4. The effects of dynorphin 10 micrograms kg-1 min 1 were abolished or greatly attenuated by NMN 1.3 mg kg-1 and NML 3 mg kg-1. In contrast, the antagonists reduced only slightly the blood pressure-lowering effect of DADLE 10 micrograms kg-1 min-1 and did not reduce significantly the effects of DADLE on the plasma noradrenaline level and heart rate. 5. It was concluded that systemically administered dynorphin produces sympatho-inhibition and an ensuing fall in blood pressure by an action at peripheral receptors, in all probability presynaptic Kappa-receptors on postganglionic sympathetic nerve fibres. The effects of DADLE are more complex and may involve both central and peripheral components. PMID- 2902893 TI - Release of [3H]-noradrenaline from the sympathetic nerves to bovine mesenteric lymphatic vessels and its modification by alpha-agonists and antagonists. AB - 1. Isolated segments of bovine mesenteric lymphatic vessels were loaded with [3H] noradrenaline and its efflux in response to field stimulation examined. Vessels were attached to an isometric force transducer for the simultaneous recording of mechanical activity. 2. Field stimulation at 1, 4 and 8 Hz (0.3 ms pulses, 1 min train) increased spontaneous contraction rate and evoked 3H release up to a maximum of 4.5% of total tissue 3H at 8 Hz. Output per pulse was maximal at 4 Hz. 3. Tetrodotoxin (3 x 10(-6) M) blocked the release of 3H in response to field stimulation although the drug did not attenuate release evoked by high K+ (65 mM) solution. Field-evoked release of 3H was also absent in Ca2+ -free solution containing EGTA (1 mM). 4. When vessels were preincubated with labelled transmitter plus cocaine (5 x 10(-5) M) evoked release of 3H was absent. After preloading with [3H]-noradrenaline, cocaine (10(-6) M) potentiated both the mechanical response to field stimulation and evoked 3H release. 5. The relatively non selective alpha-adrenoceptor antagonist phentolamine (3 x 10(-6) M) and the alpha 2-antagonists yohimbine (10(-8) M) and rauwolscine (10(-6) M) significantly increased evoked 3H release at both of the frequencies examined (1 and 4 Hz). In contrast, the selective alpha 1-antagonist prazosin (10(-6) M) failed to alter 3H release to 4 Hz stimulation although release at 1 Hz was potentiated in the presence of the drug. 6. The postsynaptic excitatory response to field stimulation remained in the presence of prazosin (10(-6) M), but was converted to an inhibitory effect in the presence of phentolamine (3 x 10(-6) M), yohimbine (10(-6) M) or rauwolscine (10(-6) M). 7. Evoked 3H efflux was significantly reduced by clonidine (10(-6) M), xylazine (10(-6) M) and exogenous noradrenaline (5 x 10(-7) M), although phenylephrine (10(-6) M) reduced release only at the lower of the two frequencies tested (1 Hz). 8. These findings suggest that release of 3H by field stimulation reflects endogenous transmitter release and that this is subject to autoinhibition via feedback onto inhibitory prejunctional alpha 2-adrenoceptors. The postjunctional excitatory response is mediated via postjunctional alpha 2-adrenoceptors. PMID- 2902894 TI - alpha-Methyldopa produces mydriasis in the rat by stimulation of CNS alpha 2 adrenoceptors. AB - 1. The effects of i.v. administration of alpha-methyldopa (MD) on rat pupil diameter were investigated. All experiments were carried out in rats in which vagosympathetic nerve trunks were sectioned bilaterally at the cervical level. 2. In anaesthetized rats MD produced a marked dose-related increase in pupil diameter. The onset of pupillary response to MD was gradual and reached maximal levels 2-3 h after administration. 3. Pretreatment with alpha 2-adrenoceptor antagonists yohimbine (1.5 mg kg-1, i.v.) or idazoxan (0.5 mg kg-1, i.v.) blocked the pupillary response to MD. In contrast, the alpha 1-antagonists prazosin (1.0 mg kg-1, i.v.) and phenoxybenzamine (1.5 mg kg-1, i.v.) did not significantly alter the pupillary effects of MD. 4. Selective enzymatic blockade with 3-hydroxy benzyl-hydrazine (NSD-1015; 25 mg kg-1, i.p.), a dopa-decarboxylase inhibitor, as well as bis (4-methyl-homopiperazinyl-thiocarbonyl) disulphide (FLA-63, 5.0 mg kg 1, i.p.), a dopamine-beta-hydroxylase inhibitor, prevented the mydriatic effect of MD. 5. The above findings support the hypothesis that MD produces a clonidine like CNS mydriasis in the rat. This effect appears to be mediated primarily by the MD metabolite, alpha-methylnoradrenaline. 6. These results indicate that MD produces mydriasis in the rat by a CNS action. The mydriatic action of MD appears to be produced by its metabolite alpha-methylnoradrenaline which in turn stimulates CNS postsynaptic alpha 2-adrenoceptors. PMID- 2902895 TI - Interactions of benztropine, atropine and ketamine with veratridine-activated sodium channels: effects on membrane depolarization, K+-efflux and neurotransmitter amino acid release. AB - 1. The effect of benztropine, atropine and ketamine on veratridine-induced efflux of K+, membrane depolarization and release of amino acid neurotransmitters was investigated in the preparation of rat brain synaptosomes. 2. All three drugs inhibited in a concentration-dependent manner the processes measured: the most effective compound was benztropine which exhibited an approximate Kd of 2 microM. The inhibition was not competitive in nature. 3. The veratridine titration curves in the presence of drugs were sigmoid with Hill coefficients of about 1.4. 4. At higher concentrations, benztropine, atropine and ketamine blocked uptake of amino acid neurotransmitters into synaptosomes. 5. It is postulated that benztropine, atropine and ketamine interfere with the veratridine-activated influx of sodium into synaptosomes through voltage-dependent channels by acting at the same site as local anaesthetics. Interactions at this site alter allosterically binding and action of veratridine. In addition, at higher concentrations the drugs interact with the carrier proteins for amino acid neurotransmitters and block their transport. PMID- 2902896 TI - Actions of dopamine antagonists on stimulated striatal and limbic dopamine release: an in vivo voltammetric study. AB - 1. Fast cyclic voltammetry at carbon fibre microelectrodes was used to study the effects of several dopamine antagonists upon stimulated dopamine release in the rat striatum and nucleus accumbens. 2. In both nuclei, stimulated dopamine release was increased by D2-receptor-selective and mixed D1/D2-receptor antagonists. The D1-selective antagonist SCH 23390 had no effect. 3. Striatal and limbic dopamine release were elevated by cis- but not trans-flupenthixol. 4. The 'atypical' neuroleptics (clozapine and thioridazine) did not cause a selective elevation of dopamine release in the limbic terminal region, whereas the non antipsychotic drug metoclopramide increased dopamine release more in striatum than nucleus accumbens. 5. We conclude from this study that striatal and limbic dopamine release are under the control of a stereoselective dopamine D2 autoreceptor on the nerve terminal and that atypical neuroleptics do not show a limbic-selective effect at this receptor after acute administration. PMID- 2902897 TI - Effect of sulphasalazine and its metabolites on mitogen induced transformation of lymphocytes--clues to its clinical action? AB - The effects of sulphasalazine (SASP), sulphapyridine (SP), and 5-aminosalicylic acid (5-ASA) have been studied on mouse spleen cells cultured in the presence of phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and lipopolysaccharide (LPS). SASP exhibited a significant degree of suppression, at doses in the range 25-100 micrograms/ml (p less than 0.01), this suppression being greater than 50% at 50 micrograms/ml. SP exhibited only a minor degree of suppression (10% at 75 micrograms/ml, p less than 0.01). Coadministration of a non-steroidal anti-inflammatory drug (NSAID), indomethacin, produced no evidence of further suppression in the presence of SASP or SP. Administration of SP plus 5 ASA to parallel cultures that were profoundly suppressed by the molecular equivalent amount of SASP resulted in no suppression. This implied requirement of the intact parent molecule (SASP) to produce this effect, at these concentrations. The concentration of SASP required to produce more than 50% suppression was higher than that ever attained in the peripheral blood of humans receiving therapeutic doses of the drug. Human lymphocytes are similarly suppressed by SASP, but only at higher concentrations than are required for murine cells. Thus, if the parent drug is the active moiety and requires these concentrations to be effective in vivo, it follows that the site where these effects may be mediated is likely to be the intestinal tract. The effects described would suggest the gut associated lymphoid tissue as a likely target. PMID- 2902898 TI - Functional heterogeneity of the cerebrovascular endothelium. AB - We have investigated the heterogeneity of endothelial cells from especially two aspects. One is the biochemical and functional differences in their cerebral and peripheral vascular beds, focusing on the capillaries, in regard to the blood brain barrier properties of the endothelium in the brain. The other aspect concerns the various functional roles that the endothelial cells may play in the regulation of cerebral blood flow by vasoactive neurotransmitters, in terms of the enzymatic and morphological blood-brain barriers, the contractile properties of the capillary endothelium and the endothelium-mediated vasodilatation in the brain. PMID- 2902899 TI - Neuropeptide Y-containing neurons in the rat striatum: ultrastructure and cellular relations with tyrosine hydroxylase- containing terminals and with astrocytes. AB - The ultrastructural localization of neuropeptide Y (NPY) was comparatively examined in the dorsal (caudate-putamen) and ventral (nucleus accumbens) striatum using the peroxidase-antiperoxidase (PAP) method. In both striatal regions, NPY like immunoreactivity (IR) was detected in perikarya, dendrites and axons. The labeled perikarya were 15-25 microns in a diameter and contained large, deeply and multiply indented nuclei and prominent Nissl bodies. The labeled dendrites contained a few large (80-150 nm) dense-core vesicles, lacked detectable spines and received few afferents. These morphological characteristics of NPY-IR neurons in both areas are in close accord with previous descriptions for the medium aspiny intrinsic neurons. Axon terminals with terminals with NPY-like IR contain primarily small clear round vesicles, as seen in single or serial sections. These terminals formed junctions that lacked recognizable pre- or post- synaptic densities, but showed parallel spacing between apposed plasmalemmas at presumed synaptic clefts. Targets of the axon terminals with NPY-like IR included unlabeled somata, unlabeled proximal dendrites and labeled and unlabeled distal dendrites. The NPY-IR neurons in the caudate-putamen differed from those in the nucleus accumbens in that (1) there were no recognized appositions between labeled dendrites and labeled terminals, and (2) fewer terminals contained large dense-core vesicles. These findings are consistent with the concept that in the nucleus accumbens, the excitability of the NPY-IR neurons may be more directly modulated by NPY or another transmitter co-existing in the terminals. Catecholamines are known to co-exist with NPY in certain rostrally projecting brainstem nuclei. Therefore, in the two striatal regions, we additionally sought to determine (1) whether the NPY-IR neurons might be modulated by catecholaminergic afferents and (2) whether NPY might co-exist with catecholamines in terminals. Goat antiserum against NPY and rabbit antiserum against tyrosine hydroxylase (TH), the catecholamine-synthesizing enzyme, were simultaneously localized in single sections by PAP and immunoautoradiographic methods, respectively. Quantitative analysis in dually labeled sections from both striatal areas revealed few, if any, direct synaptic contacts between TH-labeled terminals and dendrites containing NPY-like IR. However, there was convergence of separate NPY- and TH-IR terminals on unlabeled dendrites. A few terminals in the nucleus accumbens, but not in the dorsal striatum, showed immunoreactivity methods, to TH and also contained dense-core vesicles with NPY-like IR.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2902901 TI - Effects of intrahypothalamic administration of opioid peptides selective for mu-, kappa, and delta-receptors on different schedules of water intake in the rat. AB - The effects of opioid peptides selective for mu, kappa, and delta-opioid receptors were investigated on 3 different schedules of water intake in the rat: spontaneous, deprivational (12 h), and hypertonic saline-induced drinking. Peptides were injected into the paraventricular and supraoptic hypothalamic nuclei, D-Ala2-NMePhe4-Gly(ol)-enkephalin, a mu-selective opioid agonist, tended to increase water intake in non-deprived rats, but 0.01 and 0.1 microgram significantly decreased water intake for 45 min in deprived rats, and for up to 60 min in hypertonic saline-injected rats when injected into the paraventricular hypothalamic nucleus. The kappa-selective agonist, dynorphin A1-13 (0.1, 0.3, 1.0 and 3.0 micrograms)and the delta-selective agonist, [D-Pen2,L-Pen5]enkephalin (0.3 and 3.0 micrograms) did not affect spontaneous, deprivational or hypertonic saline-induced water intakes when injected into either the paraventricular or supraoptic hypothalamic nuclei. Thus, a mu-selective opioid peptide produced dose and time-dependent effects on drinking that were pharmacologically and anatomically specific, and dependent upon the schedule of water intake. PMID- 2902900 TI - Epileptiform bursts elicited in CA3 hippocampal neurons by a variety of convulsants are not blocked by N-methyl-D-aspartate antagonists. AB - Intracellular and extracellular recordings from CA3 hippocampal neurons in vitro were used to study the ability of several NMDA (N-methyl-D-aspartate) receptor antagonists to suppress epileptiform bursts induced by NMDA and convulsants not thought to act at NMDA receptors. The antagonists, APV (D-2-amino-5 phosphonovalerate), AP-7 (D,L-2-amino-7-phosphonohepatanoate) and CPP (D,L-3[(+/ )-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid), blocked the spontaneous and evoked bursts induced by NMDA. CPP, but not APV or AP-7, prevented the development of bursts induced by Mg-free medium. The NMDA antagonists failed to block bursting induced by kainate, 7 mM K+, mast cell degranulating peptide, anoxia or spontaneous bursting. In some cases the NMDA antagonists induced spontaneous bursts or enhanced burst frequency, a proconvulsant effect. It is concluded that activation of NMDA receptors is sufficient but not necessary for burst generation in the CA3 region. PMID- 2902902 TI - AP4 inhibits chloride-dependent binding and uptake of [3H]glutamate in rabbit retina. AB - Glutamate is one of the major neurotransmitters used by primary and secondary neurons of the visual pathway in retina. AP4(2-amino-4-phosphonobutyric acid) preferentially blocks the activity of one functional subclass of retinal neurons, ON bipolar cells, apparently by acting as an agonist at a hyperpolarizing glutamate receptor. We have used in vitro binding assays to examine different subclasses of presumptive glutamate receptors in retinal membrane fractions. One subclass consists of AP4-sensitive binding sites which require calcium and chloride for maximal binding and which are inhibited by freeze-thaw procedures. In addition, AP4 inhibits chloride-dependent [3H]glutamate uptake into retinal synaptosomes and intact retina. [3H]glutamate which is accumulated via the AP4 sensitive mechanism can be subsequently released by depolarizing levels of potassium. The pharmacological selectivity of AP4-sensitive glutamate receptors on ON bipolar cells measured electrophysiologically is very similar to that of AP4-sensitive, [3H]glutamate binding and uptake, measured biochemically in subcellular fractions. These results raise the possibility that AP4-sensitive glutamate recognition sites in retina may be linked to two separate effectors, one which gates ion channels and leads to hyperpolarization, and another which acts as a glutamate transporter. PMID- 2902903 TI - Tyrosine hydroxylase-immunoreactive somata within the primate subfornical organ: species specificity. AB - The present study describes a collection of tyrosine hydroxylase-immunoreactive (TH-ir) somata within the subfornical organ (SFO) of the Cebus monkey. In contrast, no cell bodies, and only sparse TH-ir fibers, were observed within the SFO in rats. In the monkey, these TH-ir neurons were observed throughout the rostrocaudal extent of the SFO, preferentially located at its lateral and dorsal aspects. These neurons were bipolar and multipolar with long, beaded, varicose fibers emanating from the cell soma. Cebus monkeys displayed dopamine beta hydroxylase and phenylethanolamine-N-methyltransferase- immunoreactive neurons within established noradrenergic and adrenergic nuclei respectively, but not within the SFO, suggesting that the neurons which are immunoreactive for TH in this region contain dopamine. PMID- 2902904 TI - Veratridine-induced release of endogenous glutamate from rat brain cortex slices: a reappraisal of the role of calcium. AB - The efflux of endogenous glutamate from thin slices of rat brain cortex superfused in vitro with artificial cerebrospinal fluid (ACSF) was studied. Initially, glutamate efflux was very high (2.5 nmol/mg protein/min), possibly because of the cutting procedure, but declined sharply, and at 30 min of superfusion was 25 pmol/mg protein/min. In ACSF without added calcium, spontaneous glutamate efflux was always higher than that in calcium-containing medium, e.g. at 30 min it was 75 pmol/mg protein/min. Addition of 10 microM veratridine for 2 min, between 30 and 32 min of superfusion, led, in ACSF with calcium, to an increase in glutamate efflux of 288%, when the maximum efflux following veratridine is compared to the glutamate efflux that immediately preceded the application of this drug (from 25 to 97 pmol/mg protein/min), while in ACSF without added calcium, veratridine induced an increase of only 117% (from 75 to 163 pmol/mg protein/min). These results are interpreted as due to the dual effect of veratridine. In calcium-containing ACSF, veratridine increases sodium influx which depolarizes the neurons and opens voltage-sensitive calcium channels. The increased intraneuronal calcium induces glutamate release from synaptic vesicles, while increased intracellular sodium enhances the release of soluble cytoplasmic glutamate by the reverse operation of the plasma membrane, sodium-dependent glutamate carrier. In ACSF without calcium, the release of vesicular glutamate is suppressed, while the sodium-dependent mechanism remains. This appears as if veratridine-induced glutamate efflux were only partially calcium-dependent. PMID- 2902905 TI - Transient increased density of NMDA binding sites in the developing rat hippocampus. AB - Using quantitative autoradiography and membrane preparations, the density of specific glutamate and N-methyl-D-aspartic acid (NMDA) binding sites have been determined in the developing rat hippocampus. We found an abrupt reduction in the density of NMDA binding sites after P8 (postnatal day) without change in affinity. The transient expression of NMDA receptors during maturation suggests that they may play a particularly important role in synaptogenesis. PMID- 2902906 TI - Immunocytochemical evidence for glutamatergic cortico-cortical connections in monkeys. AB - Retrograde transport of horseradish peroxidase and immunocytochemical visualization of glutamate (Glu) were combined to investigate the neurotransmitter used by cortico-cortical neurons in the first (SI) and second (SII) somatic sensory areas of macaque monkeys. The majority of association and callosal neurons in SI and SII were immunoreactive for an antiGlu serum: evidence was therefore obtained in support of a role for Glu, or a closely related compound, as the synaptic transmitter used by cortico-cortical fibers. PMID- 2902907 TI - Changes in the activity of gamma-glutamyl transpeptidase induced by kainic acid and surgical lesions of the hippocampal formation in young rats. AB - To study possible functional involvement of gamma-glutamyl transpeptidase (GGT) in glutamate transmitter metabolism we lesioned putative glutamatergic structures of the rat hippocampal formation by intracerebroventricular (i.c.v.) injection of kainic acid (KA) or by surgical CA3 axotomy. Unilateral injection of KA into the left lateral cerebral ventricle of 30-day-old rats resulted in decreased GGT activity in hippocampal areas CA3, Ca1 ipsilaterally, and in the contralateral area CA1, four hours after the induction of the chemical lesion. Four days after the injection, the enzyme activity was decreased in all hippocampal areas with the exception of the contralateral dentate gyrus. Four days after bilateral i.c.v. injection of KA, lower GGT levels were found than was seen after bilateral surgical lesion of the CA3 pyramidal cell axons (Schaffer's collaterals). The surgical lesion was followed by a decrease of GGT only in the stratum pyramidale and stratum radiatum of area CA1. In contrast to the effects in 30-day-old rats, unilateral i.c.v. injection of KA on postnatal day 12 did not alter the GGT activity in any studied hippocampal area presumably because of incomplete maturation of structures required for KA vulnerability. PMID- 2902908 TI - Functional kappa-opioid receptors on oxytocin and vasopressin nerve terminals isolated from the rat neurohypophysis. AB - Opioids intrinsic to the rat neurohypophysial system act to inhibit secretion from the terminals of magnocellular neurones. Opioid receptors in the neurohypophysis are predominantly of the kappa-subtype and selective kappa agonists suppress electrically evoked release of oxytocin (OXT) and vasopressin (AVP). We have looked for the presence of functional kappa-receptors on neurohypophysial nerve terminals by examining effects of kappa-agonists on secretion from suspensions of isolated neurohypophysial nerve terminals (neurosecretosomes) retained on filters in a perifusion system. Release of both OXT and AVP evoked by K+-depolarisation was inhibited by the kappa-agonists U 50,488H (34% and 45% respectively) and dynorphin A1-13 (68% and 51% respectively). Inhibition by dynorphin A was only observed in the presence of peptidase inhibitors. The actions of both kappa-agonists were prevented by the opioid receptor antagonist naloxone. The experiments indicate the presence of kappa-receptors on terminals of OXT and AVP neurones. This receptor population is in addition to those previously described on pituicytes and those influencing release of neurohypophysial noradrenaline. PMID- 2902909 TI - The effect of K+ and glutamate receptor agonists on the membrane potential of suspensions of primary cultures of rat astrocytes as measured with a cyanine dye, DiS-C2-(5). AB - The cyanine dye DiS-C2-(5) was used to investigate the effect of K+ and glutamate receptor agonists on the membrane potential of whole populations of primary rat astrocytes in suspension. Increasing the external K+ concentration from 5 to 40 mM caused a depolarization of the cells. Ba2+ blocked the response to K+, whereas 4-aminopyridine had no effect on the depolarization. The effect of added external K+ was enhanced by the addition of the neutral K+ ionophore valinomycin. This supports the view that the membrane potential of primary astrocytes is dependent of the K+ gradient, and suggests that the membrane is not ideally permeable to K+ ions. Glutamate caused a depolarization of the cells which was not affected by Ba2+. In the presence of veratridine and ouabain no effect of glutamate was seen. The cells were also depolarized by the glutamate receptor agonists quisqualate, kainate and N-methyl-D-aspartate (NMDA). The response to kainate was blocked by kynurenate, which also diminished the depolarization caused by glutamate. NMDA was effective when added after kainate. The effect of the glutamate receptor agonists tested was generally smaller than that of glutamate itself, and a prior addition of one of the agonists diminished the response to glutamate. The results obtained suggest that cyanine dyes are well suited for investigating the behavior of whole populations of cultured primary astrocytes. PMID- 2902910 TI - Functional expression of brain cholecystokinin and bombesin receptors in Xenopus oocytes. AB - Total RNA was extracted from 15-day-old whole rat brains. Microinjection of the RNA into Xenopus laevis oocytes induced electrophysiological responsiveness to cholecystokinin-8 (CCK) and bombesin (BBS) but not to corticotropin-releasing factor (CRF) or somatostatin. The responses to CCK and BBS were similar in shape, time course, and reversal potential to that induced by receptor mediated phospholipid breakdown and that which is induced by intracellular injection of IP3. These responses were not blocked by atropine or by mianserin, did not require extracellular Ca2+ and were completely suppressed by intracellular injection of EGTA. PMID- 2902911 TI - [Is Alzheimer's senile dementia associated with the phenomena of reactive synaptogenesis in the hippocampus?]. AB - The densities of specific binding sites for glutamate or its analogue kainate were determined in the hippocampi of patients having suffered of senile dementia of the Alzheimer type (SDAT) and compared to age matched controls. The densities of sites were reduced in SDAT cases. These results indicate a lack of hippocampal plasticity in senile dementia of Alzheimer type. PMID- 2902912 TI - [Interaction of propranolol and somatostatin with the octopaminergic response of honeybee lipemia in vivo]. AB - The injection of DL-octopamine to emerging adult honey bees (1 nanomol per individual) promptly rises the haemolymph levels of steroids, diacyl and triacylglycerols (over 100% increase occurring after 10 min). Free fatty acids are then increased (by 131%) 45 mn after injections. These responses are completely abolished by 2.5 nanomol propranolol and 0.07 nanomol cyclic somatostatin. Octopamine thus seems to be more strongly involved in the lipemia than in the glycemia regulation, by contrast with noradrenaline which is, apparently, more active on carbohydrates. PMID- 2902913 TI - [Immunocytochemical study of catecholaminergic neurons in grafted mesencephalon transplanted into the hypothalamus of the rat]. AB - Mesencephalic fragments from 14 day old embryonic rat brain were transplanted into the third ventricle of adult rats neonatally treated with monosodium glutamate. From two to twelve months after grafting, the implanted tissue was still present in the ventricle and contained TH immunoreactive neurons which displayed a normal appearance at ultrastructural level. While endogenous TH containing neurons were still present in dopaminergic regions of the recipient hypothalamus, grafted mesencephalic fragments could survive and develop. They contained TH immunopositive most probably dopaminergic neurons which are able, in some cases, to innervate the host brain. This model should be of interest in the study of neuroendocrine functions of dopaminergic neurons. PMID- 2902914 TI - Slow cardioacceleration mediated by noncholinergic transmission in the stellate ganglion of the cat. AB - In C1-spinal, pentobarbital-anaesthetized or anemically decerebrated cats, the preganglionic input to the acutely decentralized right stellate ganglion was stimulated with 10- to 30-s strains at 20-40 Hz. Electrical stimulation consistently produced an increase in heart rate in the presence of blocking doses of hexamethonium and atropine or after depletion of acetylcholine from the preganglionic axons by prolonged low frequency stimulation in the presence of hemicholinium. The increase in heart rate had a delayed slow onset, lasted several minutes, and was abolished by propranolol or by section of the inferior cardiac nerve. The magnitude and duration of the heart rate increase were related to intensity, frequency, and duration of preganglionic stimulation. The response to stimulation of a given white ramus was progressively attenuated, and eventually irreversibly lost, during prolonged continuous stimulation of that ramus, while the response to stimulation of a different unstimulated ramus was unchanged. We conclude that the slow cardioacceleration results from a slow and prolonged excitation of postganglionic neurons by a noncholinergic transmitter released by the preganglionic axons. PMID- 2902915 TI - Sensitivity and adrenoceptor affinity in the mesenteric artery of the deoxycorticosterone acetate hypertensive rat. AB - This study examines vascular reactivity to alpha-adrenoceptor agonists in mineralocorticoid (deoxycorticosterone acetate (DOCA-salt) hypertensive and normotensive rats. The rats were anesthetized and the mesenteric artery was excised and cut helically into strips that were mounted in a muscle bath for the measurement of isometric force development. Addition of norepinephrine, epinephrine, phenylephrine, methoxamine, or clonidine to the bath caused contractions in all arteries. Arteries from hypertensive rats were more sensitive (lower ED50 values) to each of the agonists than arteries from normotensive rats. alpha-Adrenoceptor affinity for phentolamine (Schild analysis; norepinephrine as the agonist) in hypertensive arteries was not significantly different from that in normotensive arteries. Maximal force generation to clonidine was greater in hypertensive arteries than in normotensive arteries. These results demonstrate an augmented vascular sensitivity to several alpha-adrenoceptor agonists in DOCA hypertensive rats. This change in sensitivity is independent of a change in affinity for the adrenoceptor antagonist, phentolamine. It may be that a change in receptor number or an alteration in a post-receptor activation event accounts for this enhanced adrenoceptor responsiveness in mineralocorticoid hypertension. PMID- 2902916 TI - Taxol-induced microtubules from different sources: an ultrastructural comparison. AB - Microtubules from different sources have been isolated using 20 microM taxol. An ultrastructural comparison allowed us to reveal some differences among taxol dependent structures. In tobacco pollen tubes a characteristic system of thin filaments was associated with taxol-induced microtubules. Similar filamentous complexes were not observed in taxol-induced microtubules isolated from other sources. PMID- 2902917 TI - Fragile sites and high-resolution chromosome studies in multiple endocrine neoplasia type 2A. AB - Affected individuals from four kindreds with multiple endocrine neoplasia type 2A syndrome (MEN-2A), were studied for the possible existence of a specific fragile site that might be associated with the MEN-2A gene. The chromosomes were also examined with high-resolution banding with particular emphasis on those chromosomes (#1, 10, 20, and 22) that have been implicated by previous studies from several laboratories as being associated with this disease. There was no evidence for a unique fragile site or a unique high-resolution banding pattern in subjects with MEN-2A. These findings, in combination with all previous cytogenetic studies, indicate that it is unlikely that current techniques will be useful in developing a simple cytogenetic test for this disease. PMID- 2902919 TI - Sleep studies and rebound insomnia: methodological problems, laboratory findings, and clinical implications. PMID- 2902918 TI - Appearance and phenotypic characterization of circulating Leu 19+ cells in cancer patients receiving recombinant interleukin 2. AB - The effects of recombinant interleukin 2 (rIL-2) therapy on peripheral blood mononuclear cells expressing the Leu 19 surface marker were evaluated in 20 cancer patients. Leu 19 is a protein with a molecular weight of 220,000 expressed on 15% of normal peripheral blood mononuclear cells and is found on a majority of cells that mediate non-major histocompatibility complex-restricted cytotoxicity. Increased relative and absolute numbers of circulating Leu 19+ cells were observed in all patients receiving rIL-2. Increases in Leu 19+ cells were due in part to the development of a subpopulation of "bright" Leu 19+ cells (Leu 19b+) that possessed a higher density of membrane Leu 19 antigen than Leu 19+ cells assayed prior to therapy. Further characterization of rIL-2 induced Leu 19+ cells by dual immunofluorescence revealed considerable phenotypic heterogeneity within this population based on the coexpression of "dim" CD8 (CD8d+), CD16, and CD2 markers. The percentage of Leu 19+ CD8d+ cells was increased during rIL-2 therapy and comprised up to 60% of all circulating Leu 19+ cells. CD16+ and CD16- subsets of Leu 19+ cells were also increased by rIL-2. The density of CD16 antigen coexpression varied inversely with the density of Leu 19. Conversely, whereas the percentage of Leu 19 cells coexpressing CD2 was also increased by rIL-2 administration, the density of CD2 antigen expression was higher on the Leu 19b+ subset of cells. The development of circulating lymphokine-activated killer activity in three patients was temporally associated with the development of increased levels of circulating Leu 19+ cells. These studies demonstrate that rIL 2 administration induces preferential increases in cells expressing the natural killer and lymphokine-activated killer cell-associated marker Leu 19 and that these increases are associated with the development of circulating lymphokine activated killer activity. Furthermore, Leu 19+ cells are comprised of phenotypically heterogeneous subsets which undergo characteristic changes during rIL-2 administration. PMID- 2902920 TI - Biperiden withdrawal in schizophrenic inpatients receiving long-term antipsychotic medication. AB - In a double-blind, 4 week study, 42 chronic schizophrenic inpatients receiving antipsychotic and antiparkinsonian (AP) drugs for greater than 3 months were either switched to placebo or maintained on biperiden. In the majority of the patients no clinically apparent discomfort was observed, and only two of 21 placebo patients developed extrapyramidal side effects (EPS) severe enough to require resumption of AP therapy. No significant increase was shown in most items on EPS. Our data suggest that for the majority of patients on long-term AP medication AP drugs should be prescribed only when EPS develop. PMID- 2902921 TI - Treatment of permanent tardive dyskinesia with tiapride, a selective D2-receptor blocking agent. PMID- 2902922 TI - Antidepressant and anxiolytic activities of tianeptine: an overview of clinical trials. AB - Tianeptine is a new antidepressant effective against anxiety accompanying mood disturbances. Its clinical properties have been assessed by double-blind controlled studies (versus imipramine, amitriptyline, nomifensine, viloxazine) in depressed patients fulfilling the diagnostic criteria of the DSM III: single recurrent major depressive episodes without melancholia or psychotic features, and dysthymic disorders. The authors have concluded that tianeptine is effective in depressive disorders as shown both by depression rating scales and subjective impressions of treated patients. This improvement increases regularly with time. Seventy-eight percent of patients were considered to be "responders" at the end of the treatment with tianeptine. Antidepressant activity of tianeptine is equally present in depressive states appearing after withdrawal from alcohol. In depressed patients with anxiety, the results also reveal the efficacy of tianeptine on anxiety symptoms. Tianeptine, in addition, shows a marked action on somatic complaints. These results have been confirmed by open long-term trials, particularly in the elderly. Tianeptine can be placed in a middle position in the bipolar classification, between the sedative and stimulant antidepressants. Its antidepressant and anxiolytic properties and its action on somatic complaints make the drug particularly suitable for the treatment of the entire range of depressive symptomatology. PMID- 2902923 TI - The innervation of the renal cortex in the dog. An ultrastructural study. AB - Two cytochemical techniques were used at the ultrastructural level to study the distribution of specific axon types to different intrarenal structures in the dog. Using the chromaffin reaction to distinguish catecholaminergic fibres from other axon populations, it was found that the renal cortex of the dog is supplied only by catecholaminergic nerves. Immunostaining for tyrosine hydroxylase (TH) labelled all of the intracortical nerves, and 20% to 25% of these profiles also contained dopa decarboxylase (DDC)-immunoreactivity, indicating they were dopaminergic rather than noradrenergic. Both DDC-positive and DDC-negative axons were seen in close association (approximately 80 nm) with blood vessels and juxtaglomerular cells as well as tubular epithelial cells. The distribution of TH and DDC-immunoreactive nerves in the renal cortex is compatible with existing functional evidence indicating that both dopaminergic and noradrenergic nerves are involved in the regulation of renal blood flow, tubular reabsorption and renin release. PMID- 2902924 TI - Histamine-like immunoreactivity in photoreceptors of the compound eyes and ocelli of the flies Calliphora erythrocephala and Musca domestica. AB - Antibodies to histamine were used for immunocytochemical studies of the visual system in the flies Calliphora erythrocephala and Musca domestica. Specific immunolabeling of photoreceptors was found both in the compound eyes and ocelli of both species. In the compound eyes histamine-like immunoreactivity (HA-IR) was found in all the short visual fibers (photoreceptors R1-6) and one type of long visual fiber (photoreceptor R8). In addition, the ocellar photoreceptors also show HA-IR. In view of earlier biochemical and pharmacological/physiological findings by Elias and Evans (1983) and Hardie (1987) it thus seems likely that histamine is a neurotransmitter in insect photoreceptors. Interestingly, the second type of long visual fiber (photoreceptor R7) has recently been found to be GABA-immunoreactive (Datum et al. 1986). The two types of long visual fibers may hence use different transmitters which act on different receptors of the postsynaptic neurons in the second visual neuropil, the medulla. In addition to the photoreceptors in the retina and ocelli, we found processes of HA-IR neurons in one of the optic lobe neuropils, the lobula. This finding indicates that histamine may also be a transmitter in certain interneurons in the visual system. PMID- 2902925 TI - Mitotic recombination in the rDNA of S. cerevisiae is suppressed by the combined action of DNA topoisomerases I and II. AB - We have found that mitotic recombination within the S. cerevisiae rDNA cluster (200 tandemly repeated 9.1 kb units) is strongly suppressed and that this suppression requires the combined action of DNA topoisomerases I and II. Strains with a null mutation in the TOP1 gene (encoding topoisomerase I) or a ts mutation in the TOP2 gene (encoding topoisomerase II) grown at a semipermissive temperature show 50- to 200-fold higher frequencies of mitotic recombination in rDNA relative to TOP+ controls. Suppression of recombination is specific to the rDNA because the recombination frequency at another tandem array, the CUP1 locus, at a simple HIS4 duplication, or among dispersed repeats (MAT and HML or HMR) is not elevated in top1 or top2 mutants. The high frequency of mitotic recombination within the rDNA cluster in topoisomerase mutants shows that both TOP1 and TOP2 are required for suppression of recombination in this region of the genome. PMID- 2902926 TI - Autoregulation of a Drosophila homeotic selector gene. AB - The Deformed (Dfd) gene is a homeotic selector that functions in specifying the identity of the mandibular and maxillary segments. We have constructed transformed fly strains carrying a Dfd cDNA under the heat-inducible control of the hsp70 promoter. With these strains we can induce the ectopic expression of Dfd protein in other segments at various stages of embryonic development. We find that both early and persistent synthesis of the protein is required for the transformation of other body segments toward head segmental identity. The persistent expression of the Dfd protein requires an endogenous copy of the Dfd gene, and we show that the expression of the endogenous copy can be induced by hsDfd expression. This implies that the Dfd protein autoactivates expression from the Dfd locus during normal development. The autoactivation circuit supplies a simple mechanism that can account, in part, for the stability of the determined state controlled by Dfd. PMID- 2902927 TI - The pituitary-specific transcription factor GHF-1 is a homeobox-containing protein. AB - Growth hormone factor 1 (GHF-1) is a pituitary-specific transcription factor that plays a critical role in cell type-specific expression of the growth hormone (GH) gene. Here, we describe the isolation of bovine and rat GHF-1 cDNA clones. These cDNAs encode proteins whose molecular mass, 33K, is identical to purified GHF-1 and whose sequence agrees with a partial GHF-1 peptide sequence. The predicted GHF-1 sequence contains a region, near its C-terminus, that exhibits considerable similarity to a homeobox consensus sequence. DNAase I footprinting with bacterially expressed fusion protein containing a fragment of GHF-1 encompassing the homeobox indicates that this region of the protein functions as its DNA binding domain. Expression of GHF-1 is restricted to cells of the somatotropic lineage in the pituitary. This remarkable specificity of GHF-1 expression correlates with the selective transcription of its target, the GH gene. Other mammalian homeobox-containing proteins may function similarly as transcription factors controlling cell type-specific expression in other locations. PMID- 2902929 TI - Homeobox proteins as sequence-specific transcription factors. PMID- 2902928 TI - A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype. AB - Multiple related cis-active elements required for cell-specific activation of the rat prolactin gene appear to bind a pituitary-specific positive transcription factor(s), referred to as Pit-1. DNA complementary to Pit-1 mRNA, cloned on the basis of specific binding to AT-rich cell-specific elements in the rat prolactin and growth hormone genes, encodes a 33 kd protein with significant similarity at its carboxyl terminus to the homeodomains encoded by Drosophila developmental genes. Pit-1 mRNA is expressed exclusively in the anterior pituitary gland in both somatotroph and lactotroph cell types, which produce growth hormone and prolactin, respectively. Pit-1 expression in heterologous cells (HeLa) selectively activates prolactin and growth hormone fusion gene expression, suggesting that Pit-1 is sufficient to confer a characteristic pituitary phenotype. The structure of Pit-1 and its recognition elements suggests that metazoan tissue phenotype is controlled by a family of transcription factors that bind to related cis-active elements and contain several highly conserved domains. PMID- 2902930 TI - Activation of human T cells with the physiological regulator of protein kinase C. AB - We investigated whether sn-1,2-dioctanoylglycerol (diC8) activates highly purified human T cells. diC8's signaling activity was also compared with that of 12-O-tetradecanoylphorbol-13-acetate (TPA). diC8 and ionomycin were synergistic in promoting T-cell proliferation. The proliferative response was dependent upon an operational interleukin-2 (IL-2) system and exhibited a high degree of specificity; sn-1,2-diC8 was twice as active as racemic-1,2-diC8, and diC8 and TPA were not synergistic. diC8's signaling activity differed from that of TPA. diC8, unlike TPA, failed to elicit IL-2 receptors or proliferation, independently of ionomycin. diC8 also failed to promote the proliferation of T cells signaled with anti-CD3 or -CD2 monoclonal antibodies. Two different inhibitors of PKC, 1 (5-isoquinolinylsulfonyl)-2-methylpiperazine or staurosporine, inhibited T-cell proliferation induced with diC8 and ionomycin, but not with TPA and ionomycin. These observations, in addition to demonstrating the differential activity of diC8 and TPA, document a signaling role for diacylglycerol in the activation of normal T cells. PMID- 2902931 TI - Prevention and reversal of experimental autoimmune thyroiditis (EAT) in mice by administration of anti-L3T4 monoclonal antibody at different stages of disease development. AB - Experimental autoimmune thyroiditis (EAT) can be induced in CBA/J mice following the transfer of spleen cells from mouse thyroglobulin (MTg)-sensitized donors that have been activated in vitro with MTg. Since L3T4+ T cells are required to transfer EAT in this model, the present study was undertaken to assess the effectiveness of the anti-L3T4 monoclonal antibody (mAb) GK1.5 in preventing or arresting the development of EAT. Spleen cells from mice given mAb GK1.5 prior to sensitization with MTg and adjuvant could not transfer EAT to normal recipients and cells from these mice did not proliferate in vitro to MTg. Donor mice given GK1.5 before immunization did not develop anti-MTg autoantibody and recipients of cells from such mice also produced little anti-MTg. GK1.5 could also prevent the proliferation and activation of sensitized effector cell precursors when added to in vitro cultures. When a single injection of mAb GK1.5 was given to recipients of in vitro-activated spleen cells, EAT was reduced whether the mAb was given prior to cell transfer or as late as 19 days after cell transfer. Whereas the incidence and severity of EAT was consistently reduced by injecting recipient mice with GK1.5, the same mice generally had no reduction in anti-MTg autoantibody. Since EAT is consistently induced in control recipients by 14-19 days after cell transfer, the ability of mAb GK1.5 to inhibit EAT when injected 14 or 19 days after cell transfer indicates that a single injection of the mAb GK1.5 can cause reversal of the histopathologic lesions of EAT in mice. These studies further establish the important role of L3T4+ T cells in the pathogenesis of EAT in mice and also suggest that therapy with an appropriate mAb may be an effective treatment for certain autoimmune diseases even when the therapy is initiated late in the course of the disease. PMID- 2902932 TI - IL-2 influences the balance between immunity and unresponsiveness in the picryl (TNP) contact sensitivity system by blocking the development or action of an Lyt 2+, I-J+ T suppressor cell. AB - Mice injected with antigen (picrylated spleen cells) intravenously fail to develop contact sensitivity. However, contact sensitivity occurs if these mice are injected with IL-2. This effect of IL-2 was reproduced in vitro by taking spleen cells 2 days after injecting antigen intravenously and culturing them with either 150 u/ml recombinant IL-2 for 2 days or by pulsing with 600-1200 u/ml IL-2 at 4 degrees C for 1 hr. After 2 days in culture these antigen-exposed cells transfer contact sensitivity to naive recipients in a 24-hr experiment. However, the ability of antigen-exposed cells, pulsed with IL-2, to transfer contact sensitivity is abolished when they are incubated with unpulsed antigen-exposed cells and as few as 1/16 of their number have a significant effect. This phenomenon is specific, as normal cell or cells from mice injected with oxazolonated cells intravenously have no effect. The suppressor cells were Thy 1+, Lyt-1-, 2+, I-J+ T cells. It was concluded that IL-2 prevents the development/action of antigen-specific T suppressor cells. PMID- 2902933 TI - Natural killer cells in rhesus monkeys: properties of effector cells which lyse Raji targets. AB - Spontaneously occurring natural killer cell activity of rhesus monkey peripheral blood mononuclear cells was assayed against five human cell lines, three of which were Epstein-Barr virus (EBV) positive, including the human B cell line Raji. The lytic activity to Raji cells was high, significantly higher than to any other cell line tested. Raji cells are normally insensitive to spontaneous lysis by human NK cells, and the contrasting vigor of the rhesus monkey cytolytic activity to Raji prompted us to investigate the properties of this effector cell. We found the effector cell-mediating lysis of Raji to be nonadherent and phagocytic with lytic activity slightly enhanced in the E-rosette-forming cell (ERFC+) fraction and decreased in the ERFC- fraction. Further isolation of FcIgG receptor-positive and FcIgG receptor-negative subsets by rosetting resulted in significant enrichment of NK activity to Raji in the positive fraction and a loss of activity in the negative fraction. Depletion studies with various monoclonal antibodies (mAb's) confirmed that nearly all lytic activity was contained in the CD16+ (Leu 11b+) population, while subsets of effector cells expressed CD2 (9.6) and CD8 (OKT8). Depletion of CD4 (OKT4)-, HLADR (OKIa)-, or LFA1 (MAC-1)-positive populations failed to reduce NK activity. We compared the phenotypic properties of alloimmune effector cells exhibiting specificity for allogeneic donor targets with those exhibiting lysis of Raji targets. Results indicated that allospecific cytotoxic T lymphocytes expressed a CD16-, CD2+ phenotype, a pattern distinct from that of the effector cell population recognizing Raji targets. The presence of CD2 mAb's in the culture had no effect on NK lytic activity. In contrast, mAbs CD8 and Leu 11b were inhibitory. This would suggest a functional role for CD8 and FcIgG molecules in the lysis of Raji cells by rhesus effectors. In summary, these studies describe a distinct population of effector cells in the blood of rhesus monkeys which exhibit spontaneous lytic activity to Raji cells and exhibit the properties of NK cells. PMID- 2902934 TI - Neonatal tolerance induction to Mlsa. II. T cells induce tolerance to Mlsa. AB - We have investigated the ability of murine T cell lines to induce neonatal tolerance to Mlsa (minor lymphocyte stimulating). Mlsb mice were injected within 24 hr of birth with MHC (major histocompatibility complex) identical T cell lines generated by culturing responders from Mlsa strains with stimulators from Mlsb strains. Injected mice were tested at 6 to 8 weeks of age for responses in either primary mixed leukocyte reaction or IL-2 limiting dilution analysis. Mlsa specific responses by injected tolerant mice relative to noninjected controls were reduced by 92-98% in MLR and by 2- to 10-fold in IL-2 LDA. In contrast, responses against third-party MHC antigens by either the injected or the noninjected mice were identical. Fifty percent of all mice injected with the T cell lines were tolerant to Mlsa. These results strongly suggest that murine T cells express the Mlsa gene product. PMID- 2902935 TI - Selective decrease in Leu8-negative T cell subpopulations following treatment with recombinant interferon-alpha 2a (rIFN-alpha 2a). AB - The effects of in vivo treatment with recombinant human IFN-alpha 2a (rIFN-alpha 2a) on the distribution of T cell subpopulations were examined in 21 patients with renal cell adenocarcinoma, using two-color flow cytometry with anti-Leu8 in combination with anti-Leu2 and anti-Leu3. Other parameters indicative of immune status, such as the number and percentage of total (CD3) T cells, in vitro proliferation to mitogen, and spontaneous immunoglobulin secretion, were also measured, prior to the initiation of treatment with rIFN-alpha 2a, and during treatment. Total T cell number decreased after treatment with rIFN-alpha 2a, to a low of 54% of mean pretreatment values after 4 weeks. The CD4/CD8 ratio did not change appreciably following treatment with rIFN-alpha 2a. However, the number of Leu8-negative T cells, within both the CD4 and the CD8 T cell populations, decreased more than the number of Leu8-positive T cells. An increase in spontaneous immunoglobulin-secreting cells followed treatment with rIFN-alpha 2a. PMID- 2902937 TI - The in-vitro activity of three long-acting cephalosporins against Bacteroides fragilis, Peptostreptococcus species and Clostridium perfringens. AB - The in-vitro activity of three long-acting cephalosporins (cefotetan, cefonicid and ceftriaxone) was compared against 206 clinical isolates of Bacteroides fragilis, Peptostreptococcus species and Clostridium perfringens, using an agar dilution procedure to determine minimum inhibitory concentrations (MICs). Clindamycin was included as a comparator. Cefotetan was much more active than the two other cephalosporins against strains of Bacteroides fragilis (MIC90 16 mg/l compared with greater than 128 mg/l for the other two agents). Cefotetan also demonstrated superior activity against anaerobic cocci. All three compounds showed good activity against strains of Clostridium perfringens. Clindamycin was active against all of the test strains. PMID- 2902936 TI - Ammonium ions and glutamine inhibit sporulation of Coprinus cinereus basidia assayed in vitro. AB - Basidia of Coprinus cinereus (Schaeff.:Fr) S. F. Gray are committed to their developmental pathway, continuing through meiosis and sporulation even when excised from their parental fruit body. A technique is described which permits this in vitro differentiation to be used as a rapid, small-scale bioassay for chemicals which interfere with these morphogenetic processes. Of a range of compounds tested, only ammonium and glutamine, and some structural analogues, were able to inhibit basidium differentiation. Growth was not inhibited; instead the differentiation inhibitors caused vegetative hyphal tips to grow out from regions of the basidial apparatus expected to be in active growth during sporulation. Depending on the stage reached at the time of exposure to the inhibitors, vegetative hyphal tips emerged from the four apical sites for sterigmata, from the tips of sterigmata, from partially formed or abnormal spores, and from the basal regions of the basidium from which paraphyses would be expected to arise. The experiments show that ammonium ions and glutamine halt meiocyte differentiation. Reports of similar effects in other organisms, animals and plants as well as fungi, may imply that sporulation events are generally sensitive to ammonium inhibition. PMID- 2902938 TI - The role of N-sulfation in the N-hydroxy-2-acetylaminofluorene-mediated outgrowth of diethylnitrosamine-initiated hepatocytes to gamma-glutamyltranspeptidase positive foci in male rat liver. AB - The ability of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) to promote the appearance of gamma-glutamyltranspeptidase-positive (GGT+) foci initiated by diethylnitrosamine (DEN) was studied in a slightly modified Solt and Farber protocol. This protocol consisted of the following treatments: initiation with a single dose of DEN followed by selection/promotion with several non-necrogenic doses of N-OH-AAF and partial hepatectomy. Treatment with N-OH-AAF resulted in a 25-fold increase of the liver volume occupied by GGT+ cells as compared to controls. The role of N-sulfation of N-OH-AAF in the GGT+ foci-selecting activity of N-OH-AAF was studied using the sulfotransferase inhibitor pentachlorophenol (PCP). Inhibition of the N-sulfation pathway with PCP during selection with N-OH AAF resulted in a greater than 80% decrease in the volume occupied by GGT+ cells, without effects on the number of GGT+ foci generated with this protocol. Also, PCP reduced the number of so called oval and bile duct cells generated by the N OH-AAF/partial hepatectomy treatment. It is concluded that N-sulfation of N-OH AAF is responsible for the N-OH-AAF-mediated outgrowth of DEN-initiated hepatocytes to preneoplastic GGT+ foci. PMID- 2902939 TI - The HuT series of 'carcinogen-transformed' human fibroblast cell lines are derived from the human fibrosarcoma cell line 8387. AB - In 1977 Kakunaga reported the carcinogen-induced transformation of the diploid human fibroblast cell line KD into focus-forming, morphologically altered cells. Cell lines were developed from 15 individual foci. These exhibited an infinite lifespan in culture and all those that were tested (7/7) formed malignant tumors (sarcomas) in athymic mice. The existing cell lines, designated HuT-11 to HuT-14, have been studied intensively during the past decade as examples of human fibroblasts malignantly transformed by treatment with a chemical carcinogen, 4 nitroquinoline-1-oxide. Recently, in comparing the HuT-11, HuT-12 and HuT-14 cell lines with KD cells, McCormick and Maher (Mutat. Res., 199, 273-291, 1988) found evidence that the malignant cells could not have been derived from the latter. But, this did not rule out the possibility that as the target cells for his original study of carcinogen-induced transformation, Kakunaga had inadvertently used cells from some other, unidentified normal individual. Since the donor of such cells would not be known and the original cell line was not available, it would be impossible to determine the degree of identity between such a target cell line and the HuT cell lines. However, in the course of examining methods for such testing, we recently became aware that the isozyme pattern of these HuT cell lines was identical to that of the human fibrosarcoma-derived cell line 8387 established in 1966. We here report that the HuT cell lines and the 8387 cell line also exhibit an identical series of HLA determinants and identical restriction fragment length polymorphisms (RFLPs). Assuming that each of these three assays measures independently inherited characteristics, the chance that an unrelated donor of the fibroblasts that gave rise to the HuT cell lines happened to possess characteristics identical to those of the patient whose fibrosarcoma gave rise to the 8387 cell line is 1 x 10(-8). Therefore, we conclude that 8387 cells are the source of the malignant cells designated HuT from Kakunaga's original transformation experiment. Additional RFLP analysis, using a probe made from M13 bacteriophage DNA which detects a hyperpolymorphic 'minisatellite' pattern in human DNA, also showed that DNA from HuT-14 cells and from 8387 cells exhibit identical banding patterns, indicating that the cell lines were taken from the same individual. The latter banding patterns differed from that observed with DNA from KD cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2902940 TI - Comparison of blood-flow velocity waveforms in different coronary artery bypass grafts. Sequential saphenous vein grafts and internal mammary artery grafts. AB - Characteristics of blood-flow velocities were investigated at different sites in two types of coronary artery bypass grafts, sequential saphenous vein grafts (SSVG) and internal mammary artery grafts (IMAG). The latter appear to have the longest life span. The patency rate of the side-to-side anastomosis of the SSVG is better than that of the end-to-side anastomosis. The SSVG was anastomosed to the major diagonal branch by side-to-side anastomosis and to the left anterior descending coronary artery (LAD) by end-to-side anastomosis in 13 patients who had 75-100% and 75-90% stenoses in the LAD and major diagonal branch, respectively. IMAG anastomoses were performed to the LAD in 10 patients with 75 100% stenoses of the artery. The blood-flow velocities were measured by the 20 MHz, eighty-channel ultrasound pulsed Doppler method during surgery. In six patients in the SSVG group, we investigated the configuration of velocity profiles at the region just proximal to the side-to-side anastomosis and at the bridge portion between the side-to-side and end-to-side anastomosis. In the other seven patients, we measured the blood-flow velocity at several centimeters proximal to the side-to-side anastomosis and compared it with that in the IMAG. At the region just proximal to the side-to-side anastomosis, the velocity profile skewed toward the anastomosis side wall in all patients, and the flow velocity near the wall opposite to the side-to-side anastomosis was reversed in five of six patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2902941 TI - Cardiovascular and renal hemodynamic effects of intravenous infusions of the selective DA1 agonist, fenoldopam, used alone or in combination with dopamine and dobutamine. AB - Fenoldopam (0.1 and 0.2 microgram/kg/min i.v.) was administered to pentobarbital anesthetized dogs alone and combined with dopamine (DA) and dobutamine. Renal blood flow, heart rate, and mean arterial pressure were measured. Both dosages of fenoldopam increased renal blood flow without altering blood pressure, similar to the effects of DA (1 and 2 micrograms/kg/min). Administration of fenoldopam with only DA (1 microgram/kg/min) produced further increase in renal blood flow. After administration of phenoxybenzamine (15 mg/kg i.v.), DA produced significant increments in renal blood flow and reductions in renal vascular resistance when compared with experiments without phenoxybenzamine, suggesting even low dosages of DA exert alpha-adrenoceptor agonist activity. Dobutamine (2 and 4 micrograms/kg/min) increased renal blood flow about 37% of that produced by DA. Fenoldopam added to dobutamine produced similar increments in renal blood flow as DA. Fenoldopam did not affect the increase in cardiac contractile force produced by DA and dobutamine. Thus, fenoldopam alone or in combination with DA had no advantage over 2 and 4 micrograms/kg/min DA to further increase renal blood flow. In contrast, fenoldopam with dobutamine produced greater increments in cardiac contractile force than DA and equivalent increases in renal blood flow as DA. PMID- 2902942 TI - Assay of dipeptidyl peptidase IV in serum by fluorometry of 4-methoxy-2 naphthylamine. AB - A new fluorometric assay for determining dipeptidyl peptidase IV (DPP IV; EC 3.4.14.5) was developed. The synthetic substrate glycyl-L-proline-4-methoxy-2 naphthylamide (20 mmol/L), Tris buffer (50 mmol/L, pH 8.3), and serum (20 microL) are mixed and incubated. The reaction is stopped with citrate (100 mmol/L, pH 4.0) and the released 4-methoxy-2-naphthylamine is measured fluorometrically. The mean value of DPP IV activity in serum for 64 healthy subjects was 58 (SD 16) mumol of 4-methoxy-2-naphthylamine released per liter of serum per minute. The proposed procedure is sensitive, rapid, and accurate and can easily be automated. PMID- 2902943 TI - Haplotype analysis of classical and mild phenotype of phenylketonuria in the German Democratic Republic. AB - The restriction fragment length polymorphism (RFLP)-haplotypes have been analysed in 16 families from the northern part of the GDR at risk for classical and mild phenylketonuria (PKU). Ten different RFLP haplotypes associated with the normal and mutant phenylalanine hydroxylase (PAH) alleles were identified. Of the 32 mutant alleles analysed, 29 (90.6%) were associated with haplotypes 1, 2, 3 and 4; 53.1% of the mutant alleles were linked with haplotype 2. The distribution of RFLP haplotypes in 16 patients of clinical different PKU phenotypes (classical and mild) is reported. PMID- 2902944 TI - Takayasu's arteritis and hypertrophic osteoarthropathy: a real association? PMID- 2902946 TI - Efficacy of syrup of ipecac-induced emesis for emptying gastric contents. AB - Syrup of ipecac (SOI) is a commonly used emetic for toxic ingestions. A preliminary study was undertaken to quantify the efficacy of SOI-induced emesis. Three groups of adult subjects fasted overnight before ingestion of 1 mCi of Tc 99m human serum albumin-sucralfate. Sucralfate is minimally absorbed from the gastrointestinal tract and has a gastric clearance half-time of 90 minutes, approximately equal to that of solid foods. At 5, 30, and 60 minutes after ingestion of radiolabeled sucralfate (RSC), subjects were given a standard dose of 30 ml SOI and 240 ml of water. Gastrointestinal tract images were obtained both at the time of ingestion of RSC and 60 minutes after ingestion of SOI. Regions-of-interest were drawn and activity measured over the stomach and small bowel with correction for physical decay. Those subjects (N = 10) treated at 5 minutes after ingestion retained a mean value of 17% of the administered RSC by 60 minutes. The group (N = 5) treated at 30 minutes after ingestion retained a mean value of 41%, while those (N = 5) treated at 60 minutes retained a mean value of 56%. The results tend to confirm the efficacy of SOI-induced emesis when SOI is given promptly (i.e., 5 minutes) following ingestion, and generally support efforts to assure widespread immediate availability of SOI for toxic ingestions. PMID- 2902945 TI - Zona fasciculata cortical adenoma and adrenal medullary hyperplasia in MEN II patient: unique concurrent presentation. AB - I-131 MIBG for the localization of pheochromocytoma is a highly specific agent. In this case report, an apparent false-positive finding attributed to the presence of three zona fasciculata cortical adenomata was ultimately deduced to be due to the presence of adrenal medullary hyperplasia in this MEN patient. PMID- 2902947 TI - [Therapy of periarthropathies]. PMID- 2902948 TI - [Untoward side effects of benzodiazepines: dependence and withdrawal syndrome]. PMID- 2902949 TI - [Neurotransmitter modulation of hunger sensation]. PMID- 2902950 TI - [Thoracic pain and normal coronary arteries in mitral valve prolapse syndrome]. PMID- 2902951 TI - [Drug interactions in the treatment of arterial hypertension: an emerging problem]. PMID- 2902952 TI - [Drugs and the thyroid gland]. PMID- 2902953 TI - [Comparative study of the elimination of several specific renal enzymes in rats after oral treatment with cyclosporin A administered in 2 vehicles of different nature]. PMID- 2902954 TI - [Current trends in medical therapy of gastroduodenal ulcer]. PMID- 2902955 TI - Transport in cells and epithelia. Mechanisms and regulations. Proceedings of the 9th conference of the European Society for Comparative Physiology and Biochemistry. 16-21 August 1987, Copenhagen, Denmark. PMID- 2902956 TI - Odd behaviour of Li+ in frog skin ion transport. AB - 1. Frog skin epithelium has basolateral K+ channels that normally define the basolateral membrane potential between 80 and 100 mV. 2. The membrane mentioned also has almost silent chloride channels and a [Na+, K+, 2Cl-] cotransport, the latter probably maintains the high Cl- in the capital (also called syncytium) cells. 3. If the K+ channels are blocked by Ba2+ (or Li+) it is possible to demonstrate potential gating of the chloride channels of the basolateral membrane. 4. When the normal K+ channels are blocked, a potential-dependent K+ conductance slowly emerges. 5. If Li+ is substituted for outside Na+ the skin shows potential oscillations of about 40 mV at a frequency of about six per hour. 6. The anion channel inhibitor Indacrinone stops these oscillations. 7. The role of Cl- and K+ channels in these oscillations is discussed. 8. The transepithelial inward transport of Li+ requires the presence of Na+ and seems to be due to exchange of cellular Li+ against inside Na+ via the basolateral Na+/H+ exchanger. PMID- 2902957 TI - Human red cell volume regulation in hypotonic media. AB - 1. There is substantial evidence for a volume-sensitive KCl cotransport system in young human RBC. 2. The KCl cotransport system becomes latent on cell maturation. 3. There is a correlation between the activation of the KCl cotransporter by either pressure, NEM, ghosting or in certain anemias with disc/cup cell shape change. 4. The stretch-activated KCl transporter may be coupled to some component of the cell cytoskeleton. PMID- 2902958 TI - Volume-activated transport systems in dog red blood cells. AB - 1. When dog red blood cells are shrunken or swollen, transport pathways are activated that do not function discernibly when the cell is at normal volume. Swelling the cells turns on two pathways, a Ca-Na exchanger and a Cl-dependent K pathway. 2. Shrinking the cells activates a Na-H antiporter. 3. The passive net flow of ions through these transporters is in such a direction as to correct the perturbation of cell volume: when the cell water content has returned to normal, the transporters turn off. 4. Recently we have investigated agents that can lock or fix the volume-responsive transporters in the activated state. Na-H exchange, for example, can be fixed in the on position with either glutaraldehyde or N phenylmaleimide. 5. Ca-Na exchange can be locked on by the sulfhydryl-oxidizing agent, diamide. We have used these effects to investigate the relationships between cell volume and the transport mechanisms. 6. It is possible, for instance, to distinguish whether certain inhibitors act on the transporters per se or on the apparatus that perceives cell volume and communicates with the transporters. 7. Furthermore, in the case of the Ca-Na exchanger some indication of the membrane polypeptides involved in volume regulation has been possible, using radioactive compounds that bind covalently to sulfhydryl groups. PMID- 2902959 TI - Na+/H+ exchange and the regulation of intracellular pH in polymorphonuclear leukocytes. AB - 1. Regulation of the cytoplasmic pH(pHi) was studied in quiescent and activated human neutrophils. Acid-loaded unstimulated cells regulate pHi by activating an electroneutral Na+/H+ exchange. 2. When activated, neutrophils undergo a biphasic change in pHi: an acidification followed by an alkalinization. The latter is due to stimulation of the Na+/H+ antiport. 3. The acidification, which is magnified in Na+-free or amiloride-containing media, is associated with net H+ efflux from the cells. 4. A good correlation exists between cytoplasmic acidification and superoxide generation: inhibition of the latter by adenosine, deoxyglucose or pertussis toxin also inhibits the pHi changes. 5. Moreover, acidification is absent in chronic granulomatous disease patients, which cannot generate superoxide. 6. Regulation of pHi is essential for neutrophil function. The oxygen dependent bactericidal activity is inhibited upon cytoplasmic acidification. This can result from impairment of Na+/H+ exchange, or from influx of exogenous acid equivalents. 7. The latter mechanism may account for the inability of neutrophils to resolve bacterial infections in abscesses, which are generally made acidic by accumulation of organic acids that are by-products of bacterial anaerobic metabolism. PMID- 2902960 TI - Na/H exchange-dependent cell volume and pH regulation and disturbances. AB - 1. The role of Na/H exchange in cell volume and pH regulation is discussed. In addition the roles of Cl/HCO3 exchange and system buffers are evaluated as they relate to Na/H exchange-dependent changes in cell salt and water content and intracellular pH. 2. Data obtained from studies of Amphiuma red blood cells showed that in addition to previously reported Na/H exchange dependent volume regulation the pathway is also involved in regulating cell pH. 3. These data showed that in contrast to volume activated Na/H exchange, when the pathway is pH activated it does not deactivate as a function of cell volume. 4. Given what appeared to be mutually exclusive volume and pH regulatory functions of the Na/H exchange, we hypothesized that the pathway might play a role in hypoxic cell swelling (cytotoxic edema). 5. In studies performed on perfused rabbit hearts employing 23Na NMR we were able to observe that relative to normoxic controls hypoxic hearts exhibited a five-fold increase in intracellular Na content when the Na-K pump was inhibited by ouabain and/or K-free perfusate. 6. These studies lead us to conclude that hypoxia-induced Na uptake is the result of an increased inward Na leak as opposed to decreased Na pumping. 7. Based upon studies with a variety of inhibitors of dissipative Na transport, we conclude that the increased inward Na leak in hypoxic hearts is via Na/H exchange. PMID- 2902961 TI - Solute transport and epithelial cell volume regulation. AB - 1. The regulation of epithelial cell volume is an essential requirement for normal tissue function and the maintenance of cellular integrity. 2. Renal papillary epithelial cells utilize an organic to compensate for the shrinkage associated with exposure to hypertonic solutions. 3. These cells synthesize the polyol, sorbitol, to increase their intracellular solute content. 4. Sorbitol is synthesized from glucose by the enzyme aldose reductase; exposure of the cells to hypertonic media causes aldose reductase synthesis and subsequent sorbitol generation over a two or three day period. 5. The intracellular signal for the formation of aldose reductase is not yet identified. PMID- 2902962 TI - Fermentation of polysaccharides and absorption of short chain fatty acids in the mammalian hindgut. AB - 1. Hindgut volume varies considerably between carnivores, omnivores and herbivores. But a common feature in all mammals is an extensive microbial fermentation of polysaccharides in the hindgut. Large amounts of short chain fatty acids (SCFA) are produced. Total concentrations of SCFA are generally ca 100 mmol/l. SCFA metabolism contributes considerably to the energy metabolism of the animal. 2. In hindgut fermenting herbivores ileal outflow provides fluid and the buffering capacity essential for microbial metabolism. 3. SCFA are rapidly absorbed. Absorption is passive and, unexpectedly, nearly independent from luminal pH. This is attributed to the presence of a constant pH-microclimate at the epithelial surface. 4. The permeability of the proximal compared to the distal colon of guinea pig is higher for acetate, equal for propionate and lower for butyrate. This difference is due to partial absorption of SCFA in the dissociated form in the proximal segment. 5. Protons required for SCFA transport in the undissociated form may be partially explained by HCO3 accumulation or by Na-H exchange. Findings are controversial. PMID- 2902963 TI - Transport of Na and Cl across the epithelium of ruminant forestomachs: rumen and omasum. A review. AB - Rumen: 1. It is generally accepted that sodium and chloride is transported across the rumen epithelium of ruminants in the mucosal-serosal direction by an active transport mechanism. In all in vitro studies the short circuit current, Isc, was significantly lower than the net transport of sodium, JNanet. It was concluded that most of the sodium is transported by an electrically silent mechanism. A Na, Cl cotransport and/or a double exchange system Na/H and Cl/HCO3 was proposed. 2. Recent in vitro studies in our laboratory revealed that the Na/H exchange inhibitor amiloride (1 mmol/l) reduced JNanet by 70%. The Na/K/2Cl-cotransport inhibitor bumetanide or furosemide (1 mmol/l) had no effect. 3. Replacement of permeable anions led to an inhibition of JNanet by 87%. However, under these experimental conditions Isc and JNanet were not significantly different. The remaining small electrogen transport of sodium was not influenced by mucosal amiloride. 4. It is concluded that two transport systems are operating in the ruminal epithelium: a Na/H exchange system which accounts for 80-90% of JNanet and an electrogen Na transport which is not sensitive against amiloride. Omasum: 1. The data concerning the transport of sodium and chloride in the omasum are very limited. In vivo measurements of flow rates demonstrated that sodium is absorbed by the omasum (40-60% of inflow in bull calves, 10-20% in sheep) and chloride is secreted. 2. In vitro studies with isolated preparation of sheep omasum epithelium demonstrated a net transport of Na and Cl in the mucosal serosal direction. JNanet is completely abolished by ouabain (0.1 mmol/1) and JClnet by replacement of Na. PMID- 2902964 TI - Postnatal development of transport function in the pig intestine. AB - 1. In the newborn pig it appears that only prenatally produced enterocytes are capable of absorbing large amounts of protein. 2. The ability of the small intestine to transport sodium, lysine, lysine containing dipeptides and glucose declines markedly during the first week of post natal life. 3. Dexamethosone causes a doubling of the sodium dependent portion of alanine uptake. 4. EGF given between days three and six of postnatal life increases sucrase and maltase activity in the distal region of the small intestine. 5. Weaning induced problems are probably not due to direct inhibition of transport properties. PMID- 2902965 TI - Modulation of Na and Cl transport by mineralocorticoids. AB - 1. The epithelia of the hen lower intestine show a Na-channel, Na-cotransport, chloride cells, and chloride absorption and secretion. 2. The short circuit current is affected by low salt levels, amiloride, glucose, lysine, leucine, galactose, ouabain, bumetanide, aldosterone, dexamethasone and spironolactone. 3. The properties of the different sodium and chloride channels are described. PMID- 2902966 TI - Transport function and control in bird caeca. AB - 1. The paired caeca at the junction of the ileum and rectum help determine the ionic composition of the voided excreta. 2. The caeca play a role in the transport of water, sodium, potassium, and chloride, the dominant effect being that of sodium transport. PMID- 2902967 TI - Nervous control of intestinal fluid transport: physiology and pathophysiology. AB - 1. The enteric nervous system (10(8) neurones in man) consists of the myentric plexus, the submucosal plexus and other minor plexuses. Eighteen different chemicals are candidates for the role of neurotransmitters in the ENS. 2. The ENS together with the autonomic nervous system and the hormonal system controls gut epithelial transport systems. PMID- 2902968 TI - The antisecretory factors: inducible proteins which modulate secretion in the small intestine. AB - 1. Cholera toxin and glucose induce the synthesis of antisecretory factors (ASF) of isoelectric points 5.0 and 4.3, respectively, and of a molecular mass of ca 60,000. 2. ASF, in nanogram amounts, inhibit intestinal secretion induced by cholera toxin, Campylobacter toxin, E. coli heat-stable toxin, C. difficile toxin A, and Dinophysis toxin. 3. Intraspinal injection of cholera toxin and glucose induces the synthesis of pituitary ASF much more effectively than does either peroral or intranasal administration. 4. Cholera toxin and glucose seem to act synergistically while inducing ASF. 5. Vagotomy abolishes both the intestinal effects of ASF and the peroral, but not the intraspinal induction of pituitary ASF. 6. ASF has no effect on ion transport across isolated intestinal mucosa from either pig or hen. 7. The results suggest that both the induction and the intestinal effects of ASF are mediated via the central and intestinal nervous system. PMID- 2902969 TI - Sodium and chloride transport across the molluscan gut. AB - 1. Na+ absorption across Aplysia gut was mediated by a Na+/K+-ATPase located in the enterocyte basolateral membrane. 2. In the absence of Na+ in the bathing medium, net Cl- absorption across Aplysia gut wall was identical to the SCC. 3. Intracellular Cl- was at a lower electrochemical potential in Aplysia enterocytes than in either the mucosal or serosal medium. 4. Cl--stimulated ATPase activity was localized in the basolateral membrane of Aplysia enterocytes. 5. ATP dependent Cl- transport was localized in the basolateral membrane of Aplysia enterocytes. 6. In Aplysia gut primary active transport systems for both Na+ and Cl- are postulated based on the evidence presented. PMID- 2902970 TI - Sodium-coupled sugar and amino acid transport in an acidic microenvironment. AB - 1. Nutrient transport mechanisms of lobster hepatopancreatic epithelial brush border membrane vesicles (BBMV) are strongly influenced by the acidic nature of the tubular lumen. 2. Sodium-dependent glucose uptake by BBMV was electrogenic and was stimulated at low pH by reducing sugar transport Ki, without affecting JM. 3. Glutamate was largely transported in zwitterionic form at pH 4.0 by an electrically silent cotransport mechanism with both Na and Cl. 4. Increased H+ concentration tripled the apparent membrane permeability to glutamate as well as the amino acid transport JM. 5. At pH 4.0 leucine was transported as a cation by two dissimilar carrier systems: a Na-independent process shared by polar amino acids, and an electroneutral Na-2Cl-dependent mechanism shared with non-polar amino acids. 6. A model is proposed for hepatopancreatic BBMV at acidic pH which employs ionic chemical gradients and membrane potential as nutrient transport driving forces. PMID- 2902971 TI - Amino acid transport in the gill epithelium of a marine bivalve. AB - 1. Amino acid transport across the intestine of bivalve molluscs is reviewed. 2. Transport of alanine or taurine is dependent on the sodium gradient across the intestine. 3. The time course of the uptake of alanine into the brush border membrane vesicles is also sodium dependent. PMID- 2902972 TI - Some major transport mechanisms of insect absorptive epithelia. AB - 1. After hormonal stimulation, fluid reabsorption (JV) in locust hindgut from the KCl-rich, low-Na primary urine is driven primarily by an unusual mucosal electrogenic Cl- pump (JCl). 2. Cyclic-AMP increases JCl and also mucosal K+ and basolateral Cl- conductances, so that KCl absorption exceeds that of Na+ in rectum but not ileum. 3. Mucosal entry of Na+ occurs by exchange for NH4+ (H+), by cotransport with some neutral amino acids, and through putative channels. 4. However, transport of proline, the predominant organic substrate, is largely Na independent and drives a sizable component of Jv in rectal but not ileal segments. 5. There is evidence for hormonal control of Na+ reabsorption in ileum but not rectum. PMID- 2902973 TI - Problems of interpreting integumental D-glucose fluxes by the integument of Schistosoma. AB - 1. The parasitic trematode Schistosoma mansoni can take up glucose across its surface at a rate three times higher than the glucose uptake by the mucosal border of the rabbit ileum. 2. Washout of tritiated polyethylene glycol (M Wt 4000) indicated that it was being lost through the integument and that the gut contribution is very small. 3. There is a peripheral diffusion resistance that will profoundly influence any transepidermal solute transfer. PMID- 2902974 TI - Regulation of membrane permeability by vasopressin; activation of the water permeability pathway in toad urinary bladder by N-ethyl-maleimide. AB - 1. Vasopressin induces a rapid increase in water permeability and stimulates net sodium transport in responsive epithelia through the mediation of cAMP. 2. In amphibian urinary bladder, the increase in water permeability is dependent on an intact cytoskeleton and is associated with the exocytotic insertion of tubular vesicles containing particle aggregates (the putative water channels) into the apical membrane of the granular epithelial cells. 3. In the toad bladder, mucosal addition of NEM, 0.1 mM, elicits a slow and irreversible increase in transepithelial water flow, whilst decreasing net sodium transport. 4. The hydrosmotic response to mucosal NEM is inhibited by cellular acidification, by pretreatment with cytoskeleton-disruptive drugs, and by agents that increase cytosolic calcium. 5. Mucosal NEM potentiates the hydrosmotic response to a submaximal, but not a maximal, dose of vasopressin. 6. Mucosal NEM, like vasopressin, induces both vesicle fusion and the appearance of particle aggregates at the granular cell apical surface. 7. NEM, unlike vasopressin, does not increase cellular cAMP content. 8. Mucosal NEM appears to increase transcellular water flow by activating cellular processes normally triggered by vasopressin, at a step beyond cAMP. PMID- 2902975 TI - ADH-induced water permeability: what role for the microtubular network? AB - 1. ADH-induced intramembrane particle aggregates in the apical membrane of the epithelial cells are specifically related to water permeability in the epithelium. 2. Colchicine and nocadozole (both of which bind to tubulin) inhibit ADH-induced osmotic water flow in the amphibian bladder. 3. Microtubules may be involved in the translocation of the aggrephores prior to their insertion into the plasma membrane. PMID- 2902976 TI - Calcium modulates transepithelial potassium secretion across isolated frog skin. AB - 1. Transepithelial K+ movements across isolated frog skin consist of four components: (i) a passive component; (ii) an active inward transport of K+ which occurs via the epithelial cells; (iii + iv) two active outward-directed components, one via the skin glands, the other via the epithelial cells. 2. Incubation of frog skin in gluconate Ringer's solution activates the K+ secretion via the epithelial cells. 3. A decrease in the Ca2+ activity of the epithelial cells increases the K+ permeability of the apical membrane and reduces the K+ permeability of the basolateral membrane. PMID- 2902977 TI - Signalling in taste receptor cells: cAMP-dependent protein kinase causes depolarization by closure of 44 pS K-channels. AB - 1. In whole-cell patch-clamp recordings cytosolic cAMP causes a substantial depolarization of taste receptor cells isolated from the frog tongue. The depolarization requires the presence of ATP in the cell and is suppressed by protein kinase inhibitor. 2. The depolarization also develops in the absence of cAMP while the catalytic subunit of the kinase is allowed to diffuse into the cell in the presence of ATP. 3. In membrane patches excised from these cells the catalytic subunit is found to inactivate K-channels of 44 pS conductance, presumably by phosphorylation. 4. It appears that cAMP is one of the intracellular messengers in gustatory chemoreception, and that it causes membrane depolarization through activation of a protein kinase which controls the activity of one set of K-channels. PMID- 2902978 TI - Characterization of a purified co-transporting protein. AB - 1. A protein of mol weight 280,000 D was isolated and purified by means of a furosemide affinity gel. 2. Binding of 3H-bumetanide suggests that the protein is identical to the Na-K-2Cl co-transporter. 3. If the protein was reconstituted into a planer lipid bilayer, a Cl- -channel of 12 pS and a K+-channel of about 130 pS was observed. 4. Whether these channel activities represent a co purification of channel proteins or whether the channel activity originates from the purified and reconstituted co-transporting protein itself was discussed. PMID- 2902979 TI - Sodium cotransport systems in epithelial secretion. AB - 1. After considering the direct coupling and indirect coupling to the sodium gradient in sodium-dependent secretion across epithelia, the properties of the Na K-Cl cotransporter involved in active chloride secretion and active chloride absorption are summarized. 2. A comparison between cellular mechanism of secretion and absorption shows that the direction of transepithelial transport is determined mainly by the intracellular localization of sodium cotransport systems and sodium-independent leaks. 3. Sodium cotransport systems, performing a similar function in various epithelia or species, may provide a powerful model to study their function at a molecular level. PMID- 2902980 TI - Passive and active transport in the parietal cell. AB - 1. Models are presented for (a) HK ATPase acting in the presence of K and Cl conductances; (b) a pH regulatory system where Na/H exchange is regulated directly by second messenger and the anion exchanger is activated secondarily to the rise in cell pH; (c) vesicle fusion and K and Cl conductances activation in the gastric parietal cell. 2. It is suggested that H transport involves protonation and deprotonation of histidine groups as well as the motion of these groups relative to the membrane barrier. 3. The HK ATPase would have a voltage generating and voltage sensitive step in the forward direction. 4. Given net electroneutrality the K transport reaction would also be charge translocating and voltage sensitive. PMID- 2902981 TI - Stimulation of NaCl secretion in the rectal gland of the dogfish Squalus acanthias. AB - 1. The rectal gland of the dogfish (Squalus acanthias) secretes NaCl when stimulated by a hormone related to vasointestinal peptide. 2. Patch clamp and microelectrode techniques are used to examine the changes in membrane conductances occurring with hormonal stimulation. 3. The conductance of the "resting" cell is dominated by basolateral K+ channels. 4. Hormonal stimulation "opens" apical Cl- channels. 5. This opening of apical chloride channels appears to be mediated by cAMP-dependent phosphorylation of pre-existing closed channels. PMID- 2902982 TI - Cholinergic-induced electrolyte transport in rat parotid acini. AB - Secretory responses of parotid acini occurring within 10 sec following cholinergic stimulation were characterized. 1. Measurement of membrane potentials by means of the fluorescent dye diSC3-(5) revealed a value of approximately -59 mV, which remained unaffected on stimulation. 2. Stimulation caused a rapid net loss of 42K+ that was strongly inhibited by the "maxi" K+-channel inhibitor "charybdotoxin" present in scorpion venom. 3. It was calculated that the number of open "maxi" K+-channels per cell was approximately 40 in the unstimulated state and approximately 3000 in the stimulated state. 4. Stimulation caused a transient decrease in the acinar ATP content. 5. Intracellular pH (pHi) measured by means of the fluorescent dye, BCECF, was dependent upon the presence of extracellular HCO3- as well as Na+. Under physiological conditions pHi was 7.27 and stimulation caused a transient decrease of 0.1 pH units due to HCO3- efflux. The decrease was followed by pHi recovery mediated by a Na+/H+ exchange mechanism. PMID- 2902983 TI - Transport of sulfate and phosphate in small intestine and renal proximal tubule: methods and basic properties. AB - 1. Isolated brush border membrane vesicles, basolateral membrane vesicles, and cultured renal epithelial cells provide good material for studying transport systems. 2. The vesicle systems have been used to study the transport of labeled phosphate, sodium/phosphate cotransport, sodium/sulfate cotransport, basolateral transport of sulfate and basolateral transport of phosphate via anion exchange. 3. Cultured renal cells show sodium/phosphate cotransport and parathyroid dependent inhibition of phosphate transport. PMID- 2902984 TI - Role of Ca2+-activated K+ channel in regulation of NaCl reabsorption in thick ascending limb of Henle's loop. AB - 1. Reabsorption of NaCl in the thick ascending limb of Henle's loop involves the integrated function of the Na+,K+,Cl- -cotransport system and a Ca2+-activated K+ channel in the luminal membrane with the Na+,K+-pump and a net Cl- conductance in the basolateral membrane. 2. Assay of K+ channel activity after reconstitution into phospholipid vesicles shows that the K+ channel is stimulated by Ca2+ in physiological concentrations and that its activity is regulated by calmodulin and phosphorylation from cAMP dependent protein kinase. 3. For purification luminal plasma membrane vesicles are isolated and solubilized in CHAPS. K+ channel protein is isolated by affinity chromatography on calmodulin columns. The purified protein has high Ca2+-activated K+ channel activity after reconstitution into vesicles. 4. The purified K+ channel consists of two proteins of 51 and 36 kDa. Phosphorylation from cAMP dependent protein kinase stimulates K+ channel activity and labels the 51 kDa band. The 36 kDa band is rapidly cleaved by trypsin and may be involved in Ca2+ stimulation. 5. Opening of the K+ channel by Ca2+ in physiological concentrations and regulation by calmodulin and phosphorylation by protein kinase may mediate kinetic and hormonal regulation of NaCl transport across the tubule cells in TAL. PMID- 2902985 TI - Calcium homeostasis of epithelial cells. AB - 1. Cytosolic free Ca2+ is an important regulator of ion transport processes in epithelial cells. 2. Free Ca2+ concentration is regulated by a concerted action of Ca2+ transport systems in plasma membranes and intracellular organelles. 3. These transport systems were studied in intestinal and renal cortical cells with emphasis on the transport capacities and Ca2+ affinities. 4. Ca2+ accumulation by permeabilized cells was compared to Ca2+ uptake by isolated organelles and membrane fractions. 5. Effects induced by cell or organelle isolation methods and the influence of temperature and pH on Ca2+ transport capacities were studied. PMID- 2902986 TI - Functional reconstitution of an isolated sodium channel from bovine trachea. AB - An amiloride-sensitive Na+ channel from bovine trachea was isolated using an affinity gel and reconstituted into a planar lipid bilayer. This channel exhibited: 1. Fluctuations with long duration opening and closing times, weak voltage dependence, and a conductance of 6 pS. 2. Selectivity of at least 100 fold for Na+ over K+. 3. Saturates at a Na+ concentration of 90 mM. 4. Blocked by amiloride, 50% inhibition at 0.1 microM. PMID- 2902987 TI - Endocrine components of body fluid homeostasis. AB - 1. Linear relationships between plasma osmolality and thirst and vasopressin secretion are described in conscious dogs. 2. During water deprivation, natriuresis occurs which ameliorates the rise in plasma osmolality. 3. Increases in plasma osmolality prevent the stimulation of aldosterone secretion by angiotensin II. PMID- 2902988 TI - Neurophysiology of body fluid homeostasis. AB - 1. Oxytocin as well as vasopressin is released in rats following systemic osmotic stimulation. There is evidence that, in the rat, oxytocin is a natriuretic hormone. 2. Osmotically-induced activation of oxytocin and vasopressin cells and osmotically-induced hormone secretion are diminished by ablation of tissue in the region anterior and ventral to the third ventricle (AV3V region). 3. The nature and identity of the osmoreceptors subserving oxytocin and vasopressin release are discussed. PMID- 2902989 TI - Central and systemic antidiuretic hormone and angiotensin II in salt and fluid balance of birds as compared to mammals. AB - 1. Tonicity dominates the release of ADH with similar sensitivities (0.2-1 pg/ml per mOsm/kg) for both birds and mammals. 2. There is an inverse relationship between the volume of the extracellular fluid compartments and the plasma level of ADH. 3. Angiotensin II formation is governed by volume factors. 4. In birds the factors reducing the delivery of Na+ to the nephron distal tubules stimulate ANGII formation. 5. Mammals have a high vascular constrictor sensitivity to ADH and ANGII; there is little or no vascular sensitivity to these in birds. 6. In birds and mammals the subfornical organ and other circumventricular organs have receptors that specifically bind ANGII. 7. Dog and duck CSF levels of ADH and AII indicate their function as specific mediators of intrinsic neuronal systems controlling salt and fluid balance. PMID- 2902990 TI - The evolvement of signal systems: conformational matching a determining force stabilizing families of signal molecules. PMID- 2902991 TI - A novel group of sperm activating peptides from the sea urchin Glyptocidaris crenularis. AB - 1. Six new sperm activating peptides were purified from the egg jelly of the sea urchin Glyptocidaris crenularis and their amino acid sequences were determined as follows: Ser-Ala-Lys-Leu-Cys-Pro-Gly-Gly-Asn-Cys-Val, Lys-Leu-Cys-Pro-Gly-Gly-Asn Cys-Val, Leu-Cys-Pro-Gly-Gly-Asn-Cys-Val, Ser-Phe-Lys-Leu-Cys-Pro-Gly-Gly-Gln-Cys Val, Lys-Leu-Cys-Pro-Gly-Gly-Gln-Cys-Val and Leu-Cys-Pro-Gly-Gly-Gln-Cys-Val. 2. The peptides were specific for G. crenularis spermatozoa and caused significant increases of sperm respiration rates and sperm cyclic nucleotide concentrations at concentrations as low as 10(-10) M. 3. The addition of the peptides to intact spermatozoa resulted in the change of the apparent mol. wt of a sperm protein from 195,000 to 200,000. PMID- 2902992 TI - Binding sites for [3H]-acetylcholine and 125I-alpha-bungarotoxin in the optic ganglion of Loligo pealii. AB - 1. In the optic ganglion of Loligo pealii, binding sites for [3H]-acetylcholine (KD: 5.2 x 10(-7) M; Bmax: 1.7 x 10(-11) mol/g tissue) and 125I-alpha bungarotoxin (KD: 3.3 x 10(-9) M; Bmax: 9.7 x 10(-11) mol/g tissue) were observed. 2. Both sites are blocked by nicotinic compounds, but differ significantly in their affinity for individual ligands, with the acetylcholine site preferentially binding agonists, and the toxin site, antagonists. 3. The acetylcholine site is substantially more thermolabile than the toxin site. 4. A partial separation of the two binding activities is accomplished by sucrose density centrifugation. 5. These observations and a comparison with other tissues (Torpedo californica electroplaque; chick optic lobe; rat brain) suggest the presence, in the squid, of more than one kind of neuronal nicotinic receptor. PMID- 2902993 TI - Influence of prostaglandins on electrical and mechanical activities of gastric muscles of Bufo marinus. AB - 1. Study was performed to compare the role of prostaglandins in regulating gastric contractile activity in an amphibian model, Bufo marinus, with mammalian models. 2. The prostaglandin synthesis inhibitor, indomethacin, had little effect on spontaneous mechanical activity, but increased the force and frequency of contractions stimulated by acetylcholine. 3. PGE2 reversed the effects of indomethacin and reduced the force and frequency of contractions. These effects were concentration-dependent. 4. Intracellular measurement of membrane potential demonstrated that the effects of PGE2 could be explained by basic effects on membrane potential and slow wave activity. 5. The data shown that many similarities exist between amphibian and mammalian gastric muscles in terms of the regulatory role played by endogenous PGs. It also appears that the mechanisms of PGE2 action are similar. PMID- 2902994 TI - Effects of cadmium exposure on feeding of freshwater planktonic crustaceans. AB - 1. Effects of cadmium exposure (0.010-0.100 ppm) on food consumption and assimilation rates of crustacean zooplankton from 2 lakes were studied in laboratory using radioisotope (14C) technique. 2. The inhibiting effects were significant 48 hr after Cd-exposure, but not after 20 hr exposure. 3. Daphnia spp. were the most affected cladocerans; copepods, especially the cyclopoids, appeared less sensitive. 4. The decrease in assimilation rates was much more marked than in the consumption rates. 5. The 14C-technique offers quick and sensitive means of studying the effects of heavy metal toxicity. PMID- 2902995 TI - Effects of cadmium on consumption, assimilation and biochemical parameters of Daphnia magna: possible implications for reproduction. AB - 1. The effects of cadmium on consumption, assimilation rates and biochemical parameters of Daphnia magna were determined. 2. The consumption and assimilation rates of 14 days 1.0 ppb Cd treated animals tended to decrease slightly, the decline of these rates at 5.0 ppb Cd (14 days), however, was highly significant (P less than 0.001). 3. The assimilation efficiencies of daphnids exposed to cadmium did not significantly differ from control. 4. No notable changes in the biochemical composition of daphnids could be noticed after 7, 14 and 21 days of cadmium exposure. 5. It seems as if not one metabolic process in particular was depressed due to cadmium, but metabolic activities seemed to be inhibited on the whole. 6. Results are discussed in relation with data of a previous study on the reproduction of D. magna under cadmium stress. PMID- 2902996 TI - Effects of synthetic biologically active peptides on giant neurones identified in the left buccal ganglion of an African giant snail (Achatina fulica Ferussac). AB - 1. The effects of synthetic biologically active peptides, including Met enkephalin, substance P, oxytocin, Arg-vasopressin, proctolin and FMRFamide, on the following four buccal neurones were examined: d-LBAN (dorsal-left buccal anterior neurone), d-LBMN (dorsal-left buccal medial neurone), d-LBCN (dorsal left buccal central neurone) and d-LBPN (dorsal-left buccal posterior neurone). These peptides were examined at 10(-4) M. 2. Oxytocin excited d-LBAN and slightly excited d-LBCN, while this inhibited d-LBMN. Arg-vasopressin excited slightly d LBAN and d-LBCN, but this had some times no effect. FMRFamide inhibited d-LBAN, and slightly inhibited d-LBCN. 3. No direct synaptic connection from the two ventral cerebral giant neurones, v-LCDN and v-RCDN, to the four buccal giant neurones was found, though the two cerebral neurones innervate the cerebro-buccal connectives. PMID- 2902997 TI - Binding properties of sea anemone toxins to sodium channels in the crayfish giant axon. AB - 1. Effects of four different sea anemone toxins from Anthopleura (AP-A and AP-C), Anemonia (ATX II) and Parasicyonis (PaTX), and a scorpion toxin from Leiurus (LqTX) on crayfish giant axons were studied. 2. These toxins slowed the Na channel inactivation process, inducing a maintained Na current during a depolarizing pulse. 3. The binding rates for these toxins markedly decreased under depolarization. The decrease in AP-A binding was mainly derived from an increased dissociation rate under depolarization whereas that in PaTX binding from a reduced association rate. 4. The potential-dependent toxin binding kinetics seemed to be related to the gating mechanism of the Na channel. 5. Competitive bindings between these toxins were demonstrated. PMID- 2902998 TI - The impairment of mobility and development in freshwater snails (Physa fontinalis and Lymnaea stagnalis) caused by herbicides. AB - 1. The pulmonate freshwater snails Physa and Lymnaea and the earthworms Eisenia and Lumbricus can take up and concentrate a carbamate herbicide (chlorpropham). 2. The mobility of freshwater snails was diminished in the presence of the herbicides chlorpropham (carbamate), cycloate (thiocarbamate), pentanochlor (amide) and chloroxurone (urea derivate). 3. The egg-assemblies of Lymnaea stagnalis turned out to be suitable objects for testing the influences of herbicides upon embryonic development. 4. In the presence of chlorpropham, chloroxurone, cycloate, propanil, simazine and terbutryne, all applied in concentrations lower than in practical use, the period of egg-maturing was delayed and the total number of dead embryos increased. 5. Developing snail eggs were very sensitive towards triazine herbicides (simazine, terbutryne) reflecting in an ED50-value lower than 10(-7) M. 6. Similar herbicidal-induced effects suggested that the developing stages of snail embryos may be suitable models for the ecologically more important but experimentally less accessible earthworms. PMID- 2902999 TI - Acivicin inhibits Crithidia fasciculata growth in a serum-free medium and inactivates carbamoyl-phosphate synthetase II in vivo. AB - 1. Crithidia fasciculata was grown in a serum-free medium. 2. Twenty-six hours after addition of 2, 5, 20, 50, and 150 microM acivicin to logarithmically growing organisms, cell counts were decreased to 46, 23, 14, 9.1, and 8.6% of the control, respectively. 3. Guanosine plus cytidine (0.1 mM each) provided complete protection against growth inhibition by 5 microM acivicin. 4. Cells exposed to 10 microM acivicin showed a time-dependent, irreversible inactivation of L-glutamine dependent carbamoyl-phosphate synthetase II activity; ammonia-dependent synthetase II activity was increased up to 34% of the control. 5. Glutamine (20 mM) protected the enzyme from inactivation in vivo. 6. These results indicate that acivicin acts as an affinity analog of L-glutamine in vivo as it does in vitro. PMID- 2903000 TI - Inducing effects of chronic administration of isoproterenol on 1-acyl-sn-glycero 3-phosphate and 1-acyl-sn-glycero-3-phosphocholine acyltransferases in rat parotid salivary gland. AB - 1. In rat parotid gland, chronic administration of isoproterenol caused significant increase of linoleic acid and decrease of arachidonic acid at the sn 2 position of phosphatidylcholine. 2. The activities of 1-acyl-sn-glycero-3 phosphate and 1-acyl-sn-glycero-3-phosphocholine acyltransferases were increased 3-8-fold and 2-fold, respectively, in the parotid gland microsomes of isoproterenol-treated rat. 3. Furthermore, the specificity of these two enzymes for various acyl-CoAs was also changed by administration of isoproterenol. 4. The alteration of unsaturated fatty acid composition at the sn-2 position of phosphatidylcholine was at least in part due to the change of activity and substrate specificity of lysophospholipid acyltransferases. PMID- 2903001 TI - Hepatic phase II biotransformation in C57Bl/KsJ db/db mice: comparison to that in Swiss Webster and 129 REJ mice. AB - 1. Cytochrome P-450 concentrations were similar in male and female carrier (db/+) and diabetic (db/db) mice. Benzphetamine N-demethylase and styrene oxide hydrolase activities were 47 and 65% lower in db/+ than in db/db mice. 2. UDP Glucuronosyltransferase activity toward 1-naphthol, estrone and diethylstilbestrol was not different between db/db and db/+, but was 40% higher in db/db mice toward testosterone. 3. Glutathione S-transferase activity toward 1 chloro-2,4-dinitrobenzene and ethacrynic acid was 47 and 59% lower in db/db mice than in male db/+ mice. Female db/+ mice had similar activities to those found in diabetic animals. 4. The differences in enzyme activity between hyperinsulinemic and normal animals suggest that insulin can influence both phase I and phase II biotransformations. 5. Enzyme activities in db/+ and db/db mice were compared to those in 129 REJ and Swiss Webster mice. PMID- 2903002 TI - Species differences in the hepatic microsomal metabolism of the pyrrolizidine alkaloid senecionine. AB - 1. The comparative metabolism of the pyrrolizidine alkaloid (PA) senecionine was studied in vitro in incubations of rat, guinea pig, cow, horse, and sheep hepatic microsomes. 2. Levels of the toxic pyrrolic metabolite 6,7-dihydro-7-hydroxy-1 hydroxymethyl-5H-pyrrolizine (DHP) were higher from guinea pig incubations (39.9 nmol/mg protein) than from other species (range 0.07 to 7.5 nmol/mg); results disagree with prior studies which used nonspecific techniques and suggest that the guinea pig's resistance to certain PAs may be due to resistance to pyrrole toxicity rather than low pyrrole formation. 3. Minor differences in senecionine N oxidation and hydrolysis existed between the various species. PMID- 2903003 TI - 3-Methylcholanthrene does induce mixed function oxidase activity in hepatopancreas of spiny crab Maja crispata. AB - 1. Type II inducers (7,8-benzoflavone, benzo(a)-pyrene and 3-methylcholanthrene) as well as Aroclor 1254, significantly increase benzo(a)pyrene monooxygenase activity in crab hepatopancreas while type I inducer (phenobarbital) does not enhance benzo(a)pyrene monooxygenase activity. 2. 3-methylcholanthrene and benzo(a)pyrene treatment of crabs significantly increase cytochrome P-450 content. 3. Benzo(a)pyrene monooxygenase induction in hepatopancreas of 3 methylcholanthrene treated crabs was inhibited by simultaneous treatment with cycloheximide but not by actinomycin D. 4. Actinomycin D insensitivity can be explained involving a regulatory pattern of induction on the posttranscriptional and/or translational, rather than transcriptional level. PMID- 2903004 TI - The effects of a choline deficiency on the lipid composition and ethanol tolerance of Drosophila melanogaster. AB - 1. A reduction in the dietary concentration of choline, an essential nutrient for Drosophila melanogaster, from the optimal concentration of 80 micrograms/ml of defined medium to 8 micrograms/ml diminished the level of tissue phosphatidylcholine to less than one-third the normal level in third instar larvae without significantly altering the amount of phosphatidylethanolamine. 2. The rates of synthesis of phospholipids, triglycerides, diglycerides and monoglycerides were reduced by the choline-deficiency, and the chain length of fatty acids in lipids was shortened. 3. The activity of succinic dehydrogenase, a mitochondrial enzyme, was decreased by the deficiency, but the activities of fumarase, sn-glycerol-3-phosphate dehydrogenase, alcohol dehydrogenase, sn glycerol-3-phosphate oxidase and fatty acid synthetase were unaffected. A choline deficiency did not alter the ultrastructure of mitochondria of larval fat body cells. 4. Choline-deficient individuals were more susceptible to the toxic effects of ethanol during larval and pupal development, and less adept at utilizing ethanol as a substrate for adult tissue synthesis. PMID- 2903005 TI - Effect of metopirone-ditartrate on thermogenesis in the guinea-pig. AB - 1. Cortisol is the major corticosteroid in the guinea-pig plasma; cortisone is detected in minor concentrations. 2. An increase in the plasma cortisol level is observed during acute cold exposure. 3. After application of metopirone ditartrate the standard metabolic rate is depressed significantly at thermoneutrality. 4. In metopirone-treated guinea-pigs the cold-induced increase in heat production is depressed by 47% concomitant with a marked drop in body temperature. 5. It is concluded that the formation of cortisol is essential for regulatory heat production induced by acute cold exposure in the guinea-pig. PMID- 2903006 TI - Failure to detect changes in sarcolemma permeability in amphibian muscle following severe cellular damage. AB - 1. Isolated amphibian hearts and pectoris cutaneous muscles were exposed either to DNP or to caffeine, thereby producing severe myofilament damage. 2. No accompanying change in sarcolemma permeability was detected by monitoring either CK or LDH release or Procion yellow entry in the heart, or by Procion entry in amphibian skeletal muscle. 3. The findings are in contrast with mammalian cardiac and skeletal muscles, and confirm that the pathways leading to myofilament degradation and to the breakdown in sarcolemma organization are separate. PMID- 2903007 TI - The effect of intraperitoneally administered gold thioglucose on growth, food consumption and accumulation of gold in various organs of the chicken (Gallus domesticus). AB - 1. Gold thioglucose (GTG) was intraperitoneally injected into 10-day-old male and female chickens in a dose of 0, 0.2, 0.4 or 0.8 mg per gram of body wt. 2. Mortality of the GTG-injected chickens was 100% and 25% for doses of 0.8 and 0.4 mg/gBW respectively, in both sexes and 25% for a dose of 0.2 mg in females, which were all found within 14.5 hr after the GTG treatment. 3. Body weight gain, food consumption and food efficiency of surviving chickens for 23 days after the GTG injection were not affected by GTG in spite of dose level. 4. Gold detected in blood, heart, liver, gallbladder, spleen, proventriculus, gizzard, duodenum, kidney, pectoral muscle, small intestine, lung and brain of the dead chickens accumulated most highly in heart and followed by spleen, but in the surviving chicken a little gold was only found in liver, spleen and kidney of some GTG treated chickens. PMID- 2903008 TI - Oral administration of diltiazem decreases ventilation and metabolism of Syrian hamsters. AB - 1. Diltiazem at doses of 2.5, 25, and 50 mg/kg caused a reduction of minute ventilation of hamsters over a 60 min period compared to saline administration. 2. The decrease of ventilation was due to a fall in frequency of breathing, but predominantly due to a decrease of tidal volume. 3. The pattern of metabolic response of hamsters to diltiazem was different to the ventilatory response--but metabolic rate was decreased in all animals receiving diltiazem by 60 min compared to pregavage values. PMID- 2903009 TI - Ocular and cardiac beta-antagonism by timolol prodrugs, timolol and levobunolol. AB - Topically applied O-butyryl timolol, O-pivaloyl timolol and levobunolol (0.25 micrograms) antagonized isoproterenol-induced ocular hypotension for 8 hrs whereas timolol (0.25 micrograms) was shorter acting (4 hrs). Timolol (25 micrograms) produced greater antagonism of isoproterenol-induced tachycardia than did O-butyryl and O-pivaloyl timolol (25 micrograms). These results suggest that, at similar doses, O-butyryl and O-pivaloyl timolol produce high concentrations of timolol in ocular tissues and undergo redistribution more slowly into the systemic circulation than does topical timolol. Under certain circumstances, prodrugs may provide a mechanism for increasing selectivity and extending the duration of action in the target organ as well as decreasing systemic effects. PMID- 2903010 TI - Alteration in the histochemical presence of tyrosine hydroxylase and CGRP immunoreactivities in the eye following chronic sympathetic or sensory denervation. AB - Changes in the content of calcitonin gene-related polypeptide (CGRP) and tyrosine hydroxylase (TH) immunoreactivities in the anterior segment of the rat eye were assessed histochemically in animals subjected to sympathetic ganglionectomy or to chronic sensory denervation induced by neonatal capsaicin treatment. In the sympathectomised eyes there was a marked depletion of TH and increase in CGRP immunoreactivity while in tissue subjected to sensory denervation the reverse was found, raised presence of TH and absence of CGRP-immunostaining. The results suggest important neurotrophic influences by the host tissue or a trophic interaction of one nerve set on another. PMID- 2903012 TI - Almitrine decreases compliance of pulmonary arteries in COPD. PMID- 2903011 TI - Localization of the coagulation factor XIII A subunit gene (F13A) to chromosome bands 6p24----p25. AB - Electrophoretic studies of the genetic variation of the A subunit of coagulation factor XIII (F13A) have shown that the A subunits expressed in placenta and in the circulation are the products of the same gene locus. In situ hybridization studies with a cDNA fragment encoding the amino terminal region of the A subunit have localized the gene to bands p24----p25 on chromosome 6. This confirms previous studies that showed linkage between F13A and the major histocompatibility complex. PMID- 2903013 TI - [Current status of the research on blood component transfusion and its clinical significance]. PMID- 2903015 TI - Sulfasalazine-induced abnormal sperm penetration. PMID- 2903014 TI - Somatostatin stimulates prostaglandin production by rat gastric epithelial cells in vitro, but is not cytoprotective. AB - Whether somatostatin stimulates prostaglandin synthesis by gastric cells is controversial. Also, it is unknown whether somatostatin protects gastric cells against exogenous injury in conditions independent of systemic factors and of inhibition of gastric acid secretion. The present study was undertaken (1) to evaluate the effect of somatostatin on prostaglandin production by rat gastric epithelial cells in monolayer culture and (2) to assess whether somatostatin protects gastric cells against taurocholate- and indomethacin-induced damage in vitro. Somatostatin at concentrations of 10(-5) M and 10(-4) M significantly stimulated PGE2 and 6-keto-PGF1 alpha production by rat gastric epithelial cells but was not able to prevent damage induced by sodium taurocholate and indomethacin to rat gastric cells in monolayer culture. These results suggest that: (1) somatostatin stimulates prostaglandin synthesis by cultured rat gastric epithelial cells, but (2) is not directly protective to rat gastric epithelial cell monolayers against drug-induced damage in vitro. PMID- 2903017 TI - The influence of diffusional barriers on presystemic gut elimination. AB - A number of drugs undergo biotransformation in the gut wall or lumen. In many cases drug extraction is greater after oral administration compared with parenteral administration. This may indicate that the diffusional clearance of drug across the blood-mucosa interface is less than that across the lumen-mucosa interface. The consequence of diffusional barriers in the gut on presystemic gut elimination (PGE) have been investigated by computer simulation of a physiological pharmacokinetic model. The following was found regarding a diffusional barrier of the blood-mucosa interface: 1) it enhances PGE, 2) it invalidates certain pharmacokinetic methods to assess PGE, 3) it makes PGE sensitive to changes in drug binding in the blood, and 4) if the diffusional barrier exists for the generated metabolite but not for the drug, methods to assess drug absorption by comparing area under the curve relationships of the metabolite after oral and iv drug administration are inaccurate. PMID- 2903016 TI - Distribution of [3H]diisopropylfluorophosphate, [3H]soman, [3H]sarin, and their metabolites in mouse brain. AB - The brain area distribution of [3H]diisopropylfluorophosphate, [3H]soman, and [3H]sarin and their metabolites in mice was studied after iv administration of sublethal doses. At the appropriate time after the injection of the radiolabeled organophosphate, the mice were decapitated and their brains were dissected into seven areas. There was a relatively even distribution of the parent compounds and their metabolites in all brain areas except the hypothalamus, which contained concentrations of parent compounds the metabolites that were 2-5 times greater than those in other brain areas. Concentrations of the parent compounds and free metabolites declined steadily throughout the time course, whereas concentrations of the bound metabolites remained relatively constant between 6 and 24 hr. There was no correlation between the disposition of soman, and its metabolites, and cholinesterase inhibition in brain areas, which implicates other central mechanisms in the production of organophosphate effects. However, the higher concentrations of organophosphates and their metabolites in the hypothalamus suggest that this area might be important with respect to the pharmacological effects or the toxicity of these compounds. PMID- 2903019 TI - The disposition of [3H]diisopropylfluorophosphate in guinea pigs after inhalation. AB - The disposition of the organophosphate anticholinesterase, diisopropylfluorophosphate (DFP), was studied in guinea pigs after inhalation exposure. The tissue disposition of [3H]DFP and its metabolites was determined in the major tissues of the guinea pig from 5 min to 24 hr after treatment. [3H]DFP rapidly penetrated all tissues, where it was quickly hydrolyzed to the inactive metabolite, free [3H]diisopropylphosphoric acid ([3H]DIP), or was covalently bound to tissue in the form of bound [3H]DIP. Tissue concentrations of [3H]DFP and free [3H]DIP followed a biphasic curve, with an initial phase representing a very rapid decrease in tissue concentrations, followed by a slower phase of tissue clearance. Concentrations of free [3H]DIP generally exceeded those of [3H]DFP; however, by 4 hr the greater portion of the radioactivity in all the tissues was in the form of bound [3H]DIP. Bound [3H]DIP levels did not follow a biphasic clearance curve and declined at a slower rate than [3H]DFP and free [3H]DIP tissue levels. By 5 min the greatest accumulation of bound [3H]DIP occurred in the liver (nearly 20% of the total body burden), with a noticeably small amount in the brain (0.1%). Tissue concentrations of nonextractable radioactivity, thought to be [3H]monoisopropylphosphoric acid ([3H]MIP), were appreciable and persistent throughout the time course. Total cholinesterase activity in the brain and red blood cells was inhibited by about 90%, with plasma pseudo- and true cholinesterase activity inhibited by 99 and 97%, respectively. The time course of recovery of enzyme activity in these tissues failed to correlate with the respective tissue levels of either bound [3H]DIP or [3H]MIP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903018 TI - Effect of galactosamine-induced hepatic UDP-glucuronic acid depletion on acetaminophen elimination in rats. Dispositional differences between hepatically and extrahepatically formed glucuronides of acetaminophen and other chemicals. AB - Galactosamine (GAL) markedly depletes hepatic UDP-glucuronic acid (UDP-GA) whereas extrahepatic UDP-GA is minimally affected. This suggests that GAL predominantly inhibits hepatic glucuronidation. Therefore, the effect of GAL induced hepatic UDP-GA depletion was examined in bile duct-cannulated rats to determine the role of hepatic glucuronidation in the disposition of acetaminophen (AA). GAL markedly altered the fate of AA-glucuronide but had little or no effect upon other AA metabolites. GAL decreased the biliary excretion of AA-glucuronide up to 92%, whereas reductions in blood levels and urinary excretion of AA glucuronide did not exceed 50%. This suggests that AA-glucuronide excreted in bile is predominantly of hepatic origin whereas AA-glucuronide found in blood and urine is derived from both hepatic and extrahepatic tissues. Data in the present and previous studies [Gregus, Watkins, Thompson, Klaassen: J. Pharmacol. Exp. Ther. 225, 256, (1983)] indicate that GAL greatly reduced the biliary excretion of AA- and valproic acid-glucuronide whereas the biliary excretion of the glucuronides of phenolphthalein, iopanoic acid, bilirubin, and diethylstilbestrol was only partially decreased. This difference appears to be largely due to differential contributions by the liver and extrahepatic tissues in the glucuronidation of various compounds as well as the availability of glucuronides formed in extrahepatic tissues for biliary excretion. Specifically, the extrahepatically formed glucuronide conjugates of AA and valproic acid are not readily available for biliary excretion whereas the glucuronides of the other compounds are readily excreted into bile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903020 TI - Enantioselective disposition and protein binding of [(5,6-dichloro-9a-propyl-3 oxo-2,3,9,9a-tetrahydro-1-H-fluoren-7 -yl)-oxy] acetic acid, a new cerebral antiedemic agent, in rats. AB - [(5,6-Dichloro-9a-propyl-3-oxo-2,3,9,9a-tetrahydro-1-H-fluoren-7-y l)-oxy] acetic acid (DPOFA) is an agent capable of reducing the swelling of astroglial cells in brain tissues. In vitro studies have demonstrated that the (R)-(+)-form of DPOFA is more effective than its (S)-(-)-form in inhibiting tissue swelling. The purpose of this study is to compare the elimination kinetics of the enantiomers. A new stereoselective HPLC procedure was developed for the simultaneous quantitation of (R)-(+)- and (S)-(-)-enantiomers in plasma and bile samples. After iv administration of the racemic mixture (40 mg/kg), rats cleared the (R) (+)-enantiomer more rapidly than the (S)-(-)-isomer; time-averaged total plasma clearances were 8.88 +/- 0.55 and 4.20 +/- 0.70 ml/min/kg (mean +/- SD), respectively. Similar results were observed when the individual isomers were administered (20 mg/kg iv). Both (R)-(+)- and (S)-(-)-enantiomers were highly bound to plasma protein. The (R)-(+)-isomer had a higher unbound fraction (2%) than did the (S)-(-)-enantiomer (0.8%). The intrinsic clearance of unbound drug for (R)-(+)- and (S)-(-)-enantiomers were 434 +/- 27 and 490 +/- 84 ml/min/kg, respectively, suggesting that the differences in the elimination of the enantiomers in rats were attributable to stereoselectivity in plasma protein binding rather than to enzyme activity. In vitro studies with isolated hepatocytes supported the hypothesis that there was no stereoselectivity in metabolism of the enantiomers. PMID- 2903021 TI - Dose-response behavior of the induction of alpha 1-acid glycoprotein by phenobarbital in the dog. AB - Three-week dosing periods at one of six oral phenobarbital doses between 15 and 400 mg/day were used to achieve steady states for induction of plasma alpha 1 acid glycoprotein concentration (AGP) in beagle dogs. In this way, the characteristics of the dose-response relationship between phenobarbital concentration and the extent of induction could be evaluated. With the 400 mg/day dose of phenobarbital, AGP increased nearly 13-fold. The response of AGP was found to depend on the square of the phenobarbital concentration. Analysis of the decay of AGP when phenobarbital dosing was discontinued showed a kinetic pattern governed by multiple rate processes. This was the result of persistence of the phenobarbital, the turnover of some metabolic precursor to AGP, and the turnover of AGP itself. PMID- 2903022 TI - Ascorbic acid deficiency and hepatic UDP-glucuronyltransferase. AB - The effect of dietary ascorbic acid on hepatic microsomal UDP glucuronyltransferase (UDPGT) activity towards p-aminophenol, bilirubin, and acetaminophen was investigated. Ascorbate deficiency produced a 33% reduction in the specific activity of UDPGT towards p-aminophenol, whereas there was no difference between microsomes from ascorbate-deficient and supplemented guinea pigs in the activity towards bilirubin and acetaminophen. This suggests that the effect of the vitamin is on a specific isozyme. This reduction was correlated with the reduced quantity of hepatic microsomal cytochrome P-450, which has been previously reported for ascorbate-deficient guinea pigs. No difference was found in the apparent affinity for the substrate, p-aminophenol, or the cofactor, UDP glucuronic acid. Differences in microsomal UDPGT activity towards p-aminophenol occurred between the two groups with membrane-perturbing processes such as sonication and Triton X-100. Sonication and magnesium chloride were found to increase activity 329% in ascorbate-supplemented animals and 138% in the ascorbate-deficient group. The addition of ascorbate acid in vitro, or its analog d-isoascorbic acid, could protect against the detrimental effects of excess substrate by maintaining a linear enzymatic rate over a 30-min time period; there was no significant effect on the initial rate of hepatic microsomal UDPGT activity in the ascorbate-supplemented animals whereas there was a significant increase in the ascorbate-deficient group. Glutathione was as effective as ascorbic acid in protecting against the detrimental effects of excess substrate whereas cysteine and dimethyltetrapteridine were only partially effective. Ascorbyl-2-sulfate and alpha-tocopherol had no significant effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903023 TI - Distribution of microsomal monooxygenases in the rabbit respiratory tract. AB - The distribution of microsomal cytochrome P-450 isozymes 2, 4, 5, and 6 and the pulmonary FAD-containing monooxygenase was determined in 10 different anatomical regions of the respiratory tract using immunoblot analysis and enzymatic assays. Cytochrome P-450 isozymes 2 and 5 and the FAD-containing monooxygenase were detected by immunoblotting in all of the pulmonary and nasal samples, although levels in nasal tissues were generally much lower than those levels found in the lung. Cytochrome P-450 isozyme 4, which is generally not present in extrahepatic tissues, was detected in nasal ethmoturbinates and mucosa. Different isozymes of cytochrome P-450 appear to be responsible for the N-demethylation of benzphetamine in lung as compared with nasal tissues. Isozyme 2 is responsible for the N-demethylation of benzphetamine in the lung, whereas another isozyme, possibly isozyme 3a is responsible for N-demethylation in nasal tissues. The presence of isozyme 3a in nasal samples was indicated by the presence of high rates of aniline hydroxylation. PMID- 2903024 TI - Species-dependent binding of disopyramide enantiomers. AB - Serum protein binding of the basic enantiomers of disopyramide were studied in several animal species. (S)-(+)-Disopyramide was more highly bound than the (R)-( )-enantiomer to serum protein in the man, gorilla, and pig. The reverse was true in cow serum, and in serum and albumin from sheep. Enantioselective differences in binding were due to differences in association constants. No enantioselective differences in binding were observed in serum protein from horse and goat, or in albumin from cow and pig. Disopyramide was highly bound to two sites on horse albumin. The association constant characterizing the binding of disopyramide to the first (major) site on horse albumin was 1.3 x 10(7) M-1. At predialysis concentrations of 10(-7) M, tris-(2-butoxyethyl)phosphate displaced disopyramide from sites on horse albumin and from sites on serum protein from the horse, man, gorilla, cow, and pig. At predialysis concentrations of 10(-5) M, warfarin and diazepam had no effect on disopyramide binding in these animal species. It is concluded that the enantioselective binding of disopyramide is species dependent, the site that is responsible for the moderate to high binding of disopyramide enantiomers is probably located on alpha 1-acid glycoprotein, and the sites that bind disopyramide in the horse are located on albumin and may be unique. PMID- 2903025 TI - Disposition and metabolism of prinomide in laboratory animals. AB - The disposition and metabolism of prinomide, the 1:1 triethanolamine salt of 1 methyl-beta-oxo-alpha-(phenylcarbamoyl)-2-pyrrolepropionitrile (CGS 10787B), have been investigated in a number of animal species after single and multiple oral dosing with 14C-labeled and unlabeled drug. After single oral doses of 25 to 50 mg/kg of [14C]prinomide to mice, rats, hamsters, dogs, cynomolgus monkeys, and baboons, radioactivity was excreted primarily in urine, in the form of metabolites. However, in the mouse and monkey, fecal excretion was also significant. In the cynomolgus monkey, a radioactive dose of drug administered after multiple doses of unlabeled drug gave rise to peak plasma concentrations of radioactivity within 1 to 6 hr. Prinomide accounted for approximately 69% of this radioactivity. The terminal plasma half-life of the drug was 24 to 41 hr. Studies in rats with [14C]prinomide indicated that radioactivity was distributed rapidly to all tissues, with the highest levels being observed in blood and well perfused organs and tissues. The lowest levels were detected in fat, eyes, and brain. Tissue levels declined to less than 6% of peak values by 48 hr after dosing, the only exceptions being fat and kidney, which retained 14 and 17% of peak radioactivity, respectively. The metabolism of prinomide was qualitatively similar in all species investigated. Major metabolites identified were the phenyl ring p-hydroxy, M1, and the bicyclic spiro, M2, derivatives of the parent drug. Other common metabolites were M3, the phenyl ring p-hydroxy analog of M2 and a complete rearrangement product in the form of a succinimide derivative, M4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903026 TI - Coordinated maternal imprinting and paternal genotype determined the ultimate level of hepatic cytochrome P-450 and associated monooxygenase activities. AB - To understand the pre- and postnatal maternal influence on hepatic drug metabolism later in adult life, we have chosen to study the mouse hybrid (129/sv x LS) offspring derived from contrasting parental lines in a designated maternal environment. Results of these studies revealed that the following: 1) sex of the offspring was the major determinant for cytochrome P-450-specific content and for the activity of aryl hydrocarbon hydroxylase, testosterone 16 alpha-hydroxylase, acetanilide hydroxylase, and NADPH-cytochrome c reductase; 2) maternal factor(s) affected cytochrome P-450-specific content and the activities of acetanilide hydroxylase and aryl hydrocarbon hydroxylase but not of testosterone 15 alpha- and 16 alpha-hydroxylases or NADPH-cytochrome c reductase; 3) superimposed upon sex and maternal determination, paternal genotype significantly contributed to adult hepatic cytochrome P-450-specific content; 4) interactions between sex of the offspring and maternal factor(s) accounted for the development of testosterone 15 alpha- and 16 alpha-hydroxylase activities later in adult life; and 5) with the exception of testosterone 16 alpha-hydroxylase activity, other yet undefined factors, including the paternal genotype, contributed to most of the measured hepatic monooxygenase activities. The mechanism of coordinated maternal imprinting and paternal genotype in determining the levels of hepatic cytochrome P-450 and its associated monooxygenase activities is discussed. PMID- 2903027 TI - Foreign compound metabolism studies with human liver obtained as surgical waste. Relation to donor characteristics and effects of tissue storage. AB - An investigation has been conducted on the foreign compound-metabolizing activity of human liver collected fresh from surgery or at autopsy from cadavers 3 to 18 hr old, and the effects of low temperature storage on the foreign compound metabolizing activity of fresh human liver. The enzyme activities studied were microsomal cytochrome P-450 content, biphenyl 4-hydroxylation, benzo-(a)pyrene metabolism, halothane reduction, and 4-hydroxybiphenyl UDP-glucuronosyl transferase, as well as cytosolic thiopurine methyltransferase, thermostable (TS) phenolsulfotransferase, thermolabile (TL) phenolsulfotransferase, and 5 fluorouracil dehydrogenase. Cadaver liver was a poor source of material for metabolism studies with the majority of the enzymes investigated. There was an 84% decrease in the yield of microsomal protein, a 64% decrease in cytochrome P 450 content per mg of microsomal protein, and a 36% decrease in the biphenyl 4 hydroxylase specific activity in human cadaver liver that was a few hours old. UDP-glucuronosyl transferase showed a 70% decrease, TS phenolsulfotransferase a 84% decrease, TL phenolsulfotransferase a 97% decrease, and thiopurine methyltransferase no significant change in specific activity. The loss of activity for many of these enzymes could be simulated by keeping fresh human liver at the temperature of the body after death. Surgical waste provided a good source of fresh, histologically normal, human liver for metabolism studies. Microsomal cytochrome P-450 content showed a significant increase with the age of the liver donor. Metabolism of benzo(a)pyrene to 3-hydroxybenzo(a)pyrene and benzo(a)pyrene-7,8- and -9,10-diols showed up to 136% higher rates in fresh liver microsomes from female donors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903028 TI - Cellular and subcellular localization of a binding protein for polychlorinated biphenyls in rat lung. AB - Enriched cell populations from rat lung were isolated by use of elutriation. An in vitro ligand binding assay as well as a Western immunoblot assay were used to determine the levels of a binding protein for certain polychlorinated biphenyls (PCBs) in cytosolic preparations from these cell populations. The cell population enriched in Clara cells (30% Clara cells) contained by far the largest amount of the PCB-binding protein, 759 +/- 81 pmol/mg of cytosolic protein as judged by an in vitro ligand binding assay. Western immunoblot analysis of cytosolic preparations from the enriched cell preparations, using antibodies to the PCB binding protein, showed levels of immunoreactive material in these fractions that corresponded to the level of the PCB-binding protein as determined by the in vitro ligand binding assay. By use of the peroxidase-antiperoxidase method of immunoperoxidase staining, antibodies to the PCB-binding protein were found to stain the Clara cells in sections of paraffin-embedded rat lungs. Intense immunoperoxidase staining of the material lining the airway epithelium was also observed. The protein was predominantly localized to the secretory granules in the apical cytoplasm of the Clara cells as determined using antibodies to the protein, protein A-gold, and electron microscopy. Previous studies have shown a selective in vivo accumulation of methylsulfonyl-PCBs in Clara cells of rodent lung and the present investigation, demonstrating the presence in the Clara cells of a secretory Mr 13,000 protein that binds methylsulfonyl-PCBs with high affinity, gives further support to the contention that the protein is an important factor in determining the in vivo disposition of these compounds. PMID- 2903029 TI - Metabolism of N,N-diethyl-m-toluamide (DEET) by liver microsomes from male and female rats. Simultaneous quantitation of DEET and its metabolites by high performance liquid chromatography. AB - A simple and sensitive HPLC procedure was developed to separate and quantitate N,N-diethyl-m-toluamide (DEET) and its in vitro metabolites using a gradient elution, a reversed phase C18 column, and an internal standard. This procedure was applied to examine the metabolism of this insect repellent in liver microsomes from normal (untreated) male and female Wistar rats. At a pH of 8.6 and at a substrate concentration of 200 microM, the microsomal preparations from males degraded DEET faster than did those from females. The half-life of DEET was 10 min and 15 min, respectively. The benzylic methyl hydroxylated metabolite and the N-deethylated metabolite were determined over 2 hr in fortified microsomal suspensions. Rate constants for appearance of the metabolites showed significantly higher values for males than for females. These observations suggests that a sex difference may be present in the metabolism of DEET. PMID- 2903030 TI - Metabolism of diazepam in vitro by human liver. Independent variability of N demethylation and C3-hydroxylation. AB - The interindividual variability of diazepam metabolism was studied using human livers. The formation of N-desmethyldiazepam (NDZ) and 3-hydroxydiazepam (temazepam, TMZ), was monitored by gas chromatography. In 10 livers, Km values for NDZ and TMZ formation varied independently from each other, each by a factor of 4, from 100 to 400 microM. This variability is consistent with the presence of at least two different cytochrome P-450 species controlling formation of these metabolites. In the same livers, Vmax for NDZ and TMZ production varied 6-fold and 15-fold, respectively. PMID- 2903031 TI - Biopharmaceutical characterization of 450191-S, a ring-opened derivative of 1,4 benzodiazepine. II. Evidence for reduced first-pass extraction by rat liver. AB - The new hypnotic, 5-[(2-aminoacetamido)methyl]-1-[p-chloro-2-(o- chlorobenzoyl)phenyl]-N,N-dimethyl-1H-1,2,4-triazole-3-carboxamide hydrochloride dihydrate (450191-S), is a ring-opened derivative of 1,4-benzodiazepine that is activated by spontaneous cyclization via a labile desglycylated metabolite (191DG). Pharmacokinetic comparison between 450191-S and its primary active metabolite, 8-chloro-6-(2-chlorophenyl)-N,N-dimethyl-4H-1,2,4-triazole[1,5 a][1,4] benzodiazepine-2-carboxamide (M-1), in rats revealed that higher levels of active metabolites were produced after 450191-S administration. To find the causes for this, in vivo and in vitro experiments were performed with the focus on hepatic uptake. Study of the absorption and distribution of radioactivity after intraduodenal administration of [14C]450191-S and [14C]M-1 revealed that most of the radioactivity was in the liver, with absorption of M-1 being rapid regardless of the dose and the absorption of 450191-S being slower at higher doses. Comparison of the portal and systemic metabolite levels showed the hepatic first-pass extraction after M-1 administration to be more effective than that after 450191-S administration. This was attributed to the labile intermediate, 191DG, which reduced the first-pass extraction in the liver. This reduction was confirmed by pharmacokinetic analysis after portal injection of 191DG in vivo and by incubation with liver slices in vitro. Thus, the presence of 191DG improved the bioavailability of active metabolites after 450191-S administration. PMID- 2903032 TI - Stereoselective N-oxygenation of zimeldine and homozimeldine by the flavin containing monooxygenase. AB - The metabolism of (Z)- and (E)-zimeldine and (Z)- and (E)-homozimeldine in hepatic rat and hog microsomes is described. The major metabolite observed in all cases examined was the tertiary amine N-oxide and it was formed at a rate 7-20 times that of norzimeldine or homonorzimeldine. N-Oxygenation requires NADPH and is stimulated by n-octylamine. Thiobenzamide and methimazole significantly inhibit N-oxide formation whereas heat pretreatment of microsomes completely abolishes N-oxide formation, strongly suggesting that zimeldine N-oxygenation if solely dependent on the flavin-containing monooxygenase. Hog liver microsomes N oxygenate the Z-allylic and homoallylic tertiary amines in marked preference to the E-isomers, whereas rat liver microsomes N-oxygenate E-isomers to a greater extent than Z-isomers. Thus, opposite stereoselectivity for zimeldine N oxygenation occurs in rat liver and hog liver microsomes. PMID- 2903033 TI - Stereoselective pharmacokinetics of ketoprofen in the rat. Influence of route of administration. AB - The 2-arylpropionic acid nonsteroidal anti-inflammatory drugs are usually administered as racemates. The enantiomers may have different pharmacokinetics and the R-isomer may metabolically invert to the S-isomer. To pinpoint the kinetics of the inversion and the location in which this metabolic process takes place, racemic ketoprofen (KT) was administered to the rat. Using a stereospecific HPLC assay, the pharmacokinetics of KT were studied following 10 mg/kg iv, po, and ip doses of racemic KT to male Sprague-Dawley rats. Plasma concentrations were always greater for (S)-KT than for (R)-KT. The mean +/- SD AUC S/R ratios were 11.8 +/- 9.93 (N = 5), 11.0 +/- 2.64 (N = 4), and 33.7 +/- 11.2 (N = 5) after iv, ip, and po doses, respectively. Bile duct-cannulated rats (N = 4) had AUCs of 85.4 +/- 58.6 and 22.8 +/- 18.4 (mg/liter) hr for (S)- and (R)-KT, respectively. The percentage of conjugated drug recovered in bile was 77.9 +/- 3.77 and 11.4 +/- 2.48% of the dose as (S)- and (R)-KT, respectively. The data indicate 1) substantial stereoselectivity, 2) presystemic gastrointestinal and systemic inversion of (R)- to (S)-KT, 3) extensive elimination of drug through bile in rats, and 4) extensive reabsorption subsequent to biliary excretion. PMID- 2903034 TI - Substrate specificity and enantioselectivity of arylcarboxylic acid glucuronidation. AB - A general and sensitive HPLC method using a precolumn switching system was developed for the separation and quantification of the individual diastereoisomeric glucuronides of the 2-phenylpropionic acid optical isomers. Kinetic properties of rat liver glucuronidation of several arylcarboxylic acids (1- and 2-naphthylacetic acids, clofibric acid, (R)-(-)- and (S)-(+)-2 phenylpropionic acids) are characterized. The results show that rat liver microsomes glucuronidate 1-naphthylacetic acid more efficiently than its regioisomer (higher Vmax/Km ratio because of a 6-fold lower Km value). Furthermore, 2-phenylpropionic acid glucuronidation occurs stereoselectively and is characterized by an enantiomeric ratio R/S = 1.60. Specific inducers of different UDP-glucuronosyltransferase isoforms and the Gunn rat strain are used to define the substrate specificity of the conjugation reaction towards arylcarboxylic aglycones. Acyl glucuronide formation is induced by phenobarbital. Gunn rats are not deficient in conjugation of these arylcarboxylic acids. These results indicate that these compounds behave similarly to classically defined group 2 substrates. In addition, the stereospecificity of 2-phenylpropionic acid conjugation is unchanged by pretreatment of animals with inducers, in vitro detergent activation, and enantiomeric inhibition. This suggests that the optical isomers of 2-phenylpropionic acid can be either conjugated by the same form or very closely regulated forms of UDPGT. PMID- 2903035 TI - New aspects of metabolic conjugation of chloramphenicol. AB - New and major chloramphenicol (CP) metabolites have been isolated from the urine of goats administered [3H]CP. The CP-3-sulfoconjugate has been identified formally from its chromatographic behaviour and mass spectrometric analysis, as well as from incubations of CP with liver cytosol, using synthetic CP-conjugate as reference. Only a strong assumption is made of the identity of the CP-3 phosphoconjugate. PMID- 2903037 TI - Nonlinear tissue distribution of ouabain in rabbits. AB - Nonlinear and slow tissue distribution of ouabain was found in rabbits, and the contribution of the ouabain binding to Na+,K+-ATPase was also examined in the heart. The tissue-to-plasma concentration ratio (Kp) of ouabain in each tissue increased with time until 120 min. In addition, the Kp also depended on the plasma concentration (Cp). In the heart, Kp decreased from 12.6 +/- 1.2 to 1.9 +/ 0.2 with the increase of the Cp from 67.3 +/- 5.0 to 497 +/- d 85.2 nM. These data indicate that ouabain distributes slowly into each tissue by a saturable process. The specific binding of ouabain to cardiac Na+,K+-ATPase was measured using crude homogenates. The dissociation constant and the binding capacity were 86 nM and 2.3 nmol/ml of 0.5% homogenate, respectively. The tissue-to-plasma concentration ratio (Kp,vitro) was constructed based on these binding parameters and this explained almost 40% of the Kp obtained in vivo. These results suggest that the ouabain binding to Na+,K+-ATPase might play one of the major roles in the slow and nonlinear tissue distribution of ouabain in rabbits. PMID- 2903036 TI - Possible hemodynamic basis to urethane anesthesia-induced reductions in renal clearance. AB - The hemodynamic basis of reported urethane anesthesia-induced reductions in the clearance of some renally eliminated compounds has been investigated in the laboratory rat. The use of urethane as an anesthetic in pharmacokinetic studies still persists, particularly in experiments of long duration. Using a microsphere technique, the per cent distribution of cardiac output to the kidneys, in both ip urethane- and ip Hypnorm/Hypnovel-anesthetized animals was significantly (p less than 0.01) lower than that observed in ip pentobarbital-anesthetized animals. However, the cardiac index in the Hypnorm/Hypnovel-anesthetized animals was 42% greater (p less than 0.01) than in the pentobarbital-treated animals and 86% greater (p less than 0.01) than in the urethane-treated group. Additionally, the cardiac index in the pentobarbital-anesthetized animals was significantly greater (p less than 0.01) than in the urethane-anesthetized animals. The lower cardiac index and reduced cardiac distribution to the kidneys in the urethane-treated group resulted in significant (p less than 0.01) reductions of approximately 40% in renal blood flow and glomerular filtration rate compared with the animals anesthetized with pentobarbital or Hypnorm/Hypnovel. The transport capacity of the basolateral organic anion secretory mechanism was not compromised by an ip injection of urethane, as demonstrated by p-aminohippuric acid transport studies conducted in isolated renal tubule fragments prepared from anesthetized animals. In conclusion, urethane anesthesia results in significant alterations of renal hemodynamics compared with pentobarbital and Hypnorm/Hypnovel anesthesia in the rat. For primarily renally eliminated compounds, such alterations are likely to influence pharmacokinetic data generated using this anesthetic agent. PMID- 2903038 TI - Glucuronidation in 4-chlorobiphenyl metabolism by rat and human liver microsomes. PMID- 2903039 TI - Effect of enoxacin and 4-oxo-enoxacin on antipyrine disposition in the rat. PMID- 2903040 TI - Isotope effects on formaldehyde oxidation. PMID- 2903041 TI - [Demonstration by lymphocyte transformation test of the allergic genesis in a case of acute hepatitis]. AB - After accidental re-exposure to metamizole a 50-year-old patient developed severe jaundice within five hours (total bilirubin 43.9 mg/dl) with a rise of GOT to 147, of GPT to 222, of gamma-GT to 380 and of alkaline phosphatase to 497 U/l. The allergic genesis of this reaction was demonstrated in the lymphocyte transformation test which, in the presence of the causative substance and its metabolites, was performed five times during a period of 232 days. The first three tests were positive with stimulation indices up to 2.3. Sensitization to the metabolite 4-aminoantipyrine was demonstrated: this is known to be the first of four metabolites formed within 1-1 1/2 hours and constituting 40% of the four metabolites in the blood. PMID- 2903042 TI - The development of an assay to detect mRNAs that affect early development. AB - We have constructed an assay to identify developmental effects of injected RNA molecules. The RNA is injected into the animal pole region of a 2- to 8-cell embryo. At the blastula stage, the animal cap is removed and its development in isolation tested. In controls, only epidermis is produced, but several of the injected RNA preparations, though not all, also form dorsal and ventral mesoderm and nervous tissue. This assay should be suitable for selecting cDNA clones complementary to mRNAs that direct development. PMID- 2903043 TI - Genetics of sex determination: what can we learn from Drosophila? AB - The combined efforts of genetics, developmental and molecular biology have revealed the principles of genetic control of sexual differentiation in Drosophila. In combination with maternal components, a quantitative chromosomal signal, provided by the ratio of X chromosomes to sets of autosomes (X:A), regulates a key gene (Sxl). The functional state, ON or OFF, of Sxl, via a few subordinate regulatory genes, controls a switch gene (dsx) that can express two mutually exclusive functions, M or F. These serve to repress either the female or the male set of differentiation genes, thus directing the cells either into the male or into the female sexual pathway. Investigations of control genes and their regulation show that they have properties of homeotic genes. Their role is to select one of two alternative developmental programs. Their function, or lack of function, is required throughout development to maintain the cells in their respective sexual pathway. Differentiation genes are under negative control by dsx. We discuss the cis- and trans-regulatory elements that are needed for sex-, tissue- and stage-specific expression of the differentiation genes. A comparison of Drosophila to other organisms such as Caenorhabditis, mammals and other insects indicates similarities that we interpret as evidence for a basically invariant genetic strategy used by various organisms to regulate sexual development. PMID- 2903044 TI - [New methods in gene mapping]. PMID- 2903045 TI - Electrophysiological study in systemic necrotizing vasculitis of the polyarteritis nodosa group. PMID- 2903046 TI - Localization of the mdx mutation within the mouse dystrophin gene. AB - We have mapped human and mouse X chromosome-specific genomic and cDNA probes through an interspecies Mus musculus/spretus pedigree which contains the mdx mutation. The positions of these markers relative to one another and to the mdx mutation were delineated. Using probes corresponding to segments of the human Duchenne muscular dystrophy (DMD) gene transcript, the position of a cross hybridizing mouse equivalent gene (mDMD) was located. In more than 200 animals mapped, three were identified which show recombination within this mDMD gene. Analysis of these three animals shows that the mDMD gene is oriented with its 5' end centromeric and its 3' end telomeric on the mouse X chromosome. Furthermore, their recombinational breakpoints are on either side of the mdx mutation, thus providing the first unequivocal demonstration that the mdx mutation is located within the mDMD gene and defining limits within that gene between which the mutation must lie. Within that segment the evidence indicates that there is no major deletion of an exon as detectable by Southern blot analysis in mdx animals. The mdx mouse becomes important as an animal model for the study of the expression of the DMD gene and its developmental consequences, for transgenic and other corrective manipulations. PMID- 2903047 TI - Uptake of GABA by rat brain synaptic vesicles isolated by a new procedure. AB - Uptake of GABA was demonstrated in rat brain synaptic vesicles which were prepared by a new and efficient procedure. The uptake activity co-purified with the synaptic vesicles during the isolation procedure. The purity of the vesicle fraction was rigorously examined by analysis of marker enzymes and marker proteins and also by immunogold electron microscopy using antibodies against p38 (synaptophysin). Contamination by other cellular components was negligible, indicating that GABA uptake by the synaptic vesicle fraction is specific for synaptic vesicles and not due to the presence of other structure possessing GABA uptake or binding activities. GABA uptake was ATP dependent and similar to the uptake of glutamate, which was assayed for a comparison. Both uptake activities were independent of sodium. They were inhibited by the uncoupler carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, indicating that the energy for the uptake is provided by an electrochemical proton gradient. This gradient is generated by a proton ATPase of the vacuolar type as suggested by the effects of various ATPase inhibitors on neurotransmitter uptake and proton pumping. Competition experiments revealed that the transporters for GABA and glutamate are selective for the respective neurotransmitters. PMID- 2903049 TI - Evidence that the Abdominal-B r element function is conferred by a trans regulatory homeoprotein. AB - The Abdominal-B gene is a homeotic gene located in the distal-most region of the bithorax complex (BX-C). Based on complementation analysis it has been proposed that the gene contains two separable genetic elements, called the m and r elements. The r element has a chiefly regulatory function confined to parasegment 14. In a reverse Northern screen of the distal-most BX-C DNA, we found four distinct areas that are transcribed in the embryo. One of the transcripts spans a large genomic region which, upon disruption by rearrangement breakpoints, causes loss of r element function. This transcript is expressed in the early embryo in a single domain apparently corresponding to parasegment 14. We propose that the small homeoprotein encoded by the transcript acts as a trans-regulator to confer r element function. PMID- 2903048 TI - Developmentally regulated alternative splicing of transcripts from the Drosophila homeotic gene Antennapedia can produce four different proteins. AB - Antennapedia (Antp) is a Drosophila homeotic gene that controls differentiation of the thoracic segments. Antp transcripts are produced from either of two promoters that are independently regulated in temporally and spatially distinct patterns. In addition, Antp transcripts utilize either of two major polyadenylation sites. Antp primary transcripts contain the same protein coding sequences. Alternative RNA splicing at two positions within the primary transcripts produces mRNAs that can encode four slightly different Antp proteins. Different classes of alternatively spliced transcript predominate early and late in Drosophila development, indicating that the Antp gene is regulated by the processing of its transcripts as well as by controlling their transcription. Alternative splicing appears to be independent of which promoter and which polyadenylation site is used. PMID- 2903051 TI - The effect of inorganic pyrophosphate on the activity and Pi-binding properties of mitochondrial F1-ATPase. AB - Interaction of F1-ATPase from beef heart mitochondria with PPi has been investigated. The presence of PPi in the ATPase assay medium does not affect the initial rate of ATP hydrolysis by F1-ATPase, but slows down the decrease of enzyme activity in the course of ATP hydrolysis and increases the steady-state rate of ATP hydrolysis. Being present in the ATPase assay medium, PPi accelerates the ATP-dependent reactivation of an inactive complex formed by F1-ATPase and ADP. This inactive complex is also reactivated after preincubation with PPi. F1 ATPase, preincubated with PPi, is inactivated by azide much more slowly than is the non-preincubated enzyme. PPi stimulates the binding of Pi to F1-ATPase by decreasing mainly the Kd for Pi and only slightly raising the stoichiometry of high-affinity Pi binding. It follows from the results obtained that PPi interacts with the non-catalytic site(s) of F1-ATPase. PMID- 2903050 TI - Different transcripts of the Drosophila Abd-B gene correlate with distinct genetic sub-functions. AB - Abdominal-B (Abd-B) is a homeotic selector gene required for the correct development of abdominal segments 5-9. This gene contains at least two different genetic sub-functions which act as 'morphogenetic' or 'regulatory' elements within a single lethal complementation group. In an effort to identify the molecular nature of these sub-functions we have characterized homeobox-containing transcripts of Abd-B. The Abd-B transcripts can be grouped into four major classes whose diversity arises through differential exon splicing. We have isolated cDNAs which represent three of the transcript classes, designated alpha, beta and gamma. Their expression patterns, coupled with previous molecular genetic analyses of Abd-B, suggest that the alpha transcript class encodes the 'morphogenetic' sub-function while the beta transcript class contributes to the 'regulatory' sub-function. PMID- 2903052 TI - Selective induction of peroxisomal enzymes by the hypolipidemic drug bezafibrate. Detection of modulations by automatic image analysis in conjunction with immunoelectron microscopy and immunoblotting. AB - Quantitative immunoelectron microscopy in conjunction with quantitative analysis of immunoblots have been used to study the effects of bezafibrate (BF), a peroxisome-proliferating hypolipidemic drug, upon six different enzyme proteins in rat liver peroxisomes (Po). Antibodies against following peroxisomal enzymes: catalase, urate oxidase, alpha-hydroxy acid oxidase, acyl-CoA oxidase, bifunctional enzyme (hydratase-dehydrogenase) and thiolase, were raised in rabbits, and their monospecificities were confirmed by immunoblotting. Female Sprague-Dawley rats were treated for 7 days with 250 mg/kg/day bezafibrate and liver sections were incubated with the appropriate antibodies followed by the protein A-gold complex. The labeling density for each enzyme was estimated by automatic image analysis. In parallel experiments immunoblots prepared from highly purified peroxisome fractions of normal and BF-treated rats were incubated with the same antibodies. The antigens were visualized by an improved protein A gold method including an anti-protein A step and silver amplification. The immunoblots were also quantitated by an image analyzer. The results revealed a selective induction of beta-oxidation enzymes by bezafibrate with thiolase showing the most increase followed by bifunctional protein and acyl-CoA oxidase. The labeling density for catalase and alpha-hydroxy acid oxidase was reduced, confirming fully the quantitative analysis of immunoblots which in addition revealed reduction of uricase. These observations demonstrate that hypolipidemic drugs induce selectively the beta-oxidation enzymes while other peroxisomal enzymes are reduced. The quantitative immunoelectron microscopy with automatic image analysis provides a versatile, highly sensitive and efficient method for rapid detection of modulations of individual proteins in peroxisomes. PMID- 2903053 TI - Dopexamine hydrochloride, a beta 2 adrenergic and dopaminergic agonist; haemodynamic effects following cardiac surgery. AB - Twelve patients recovering from open heart surgery received an intravenous infusion of dopexamine hydrochloride, a novel beta 2 adrenergic and dopamine receptor agonist. The mean cardiac index increased from 2.58 to a maximum of 3.64 1 min-1 m-2 (P less than 0.001) and the systemic vascular resistance (SVR) decreased from 1527 to 1116 dyne s cm-5 (P less than 0.001) at a dose of 3 micrograms kg-1 min-1. Heart rate increased with dose from 85 beats min-1 to a maximum of 119 beats min-1 (P less than 0.001). There was no significant change in the pulmonary vascular resistance (PVR) with treatment in the group as a whole. However, PVR decreased (P less than 0.05) in patients who had aortic-valve replacement (AVR) only, whereas in patients who had mitral-valve replacement (MVR) the PVR increased (P less than 0.05). We conclude that dopexamine hydrochloride was well tolerated in patients following cardiac surgery. It produced a significant increase in cardiac output with evidence of afterload reduction and, although the increase in heart rate may limit its use in some patients, dopexamine hydrochloride is potentially of value in the treatment of low cardiac output state following cardiac surgery. PMID- 2903054 TI - Multiple sulfatase deficiency with a novel biochemical presentation. AB - Deficient activities of cerebroside-sulfatase, N-Acetylgalactosamine-4-sulfatase and iduronide 2-sulfatase in the lymphocytes of a patient suspected of metachromatic leukodystrophy, established the diagnosis of multiple sulfatase deficiency (MSD). Cultured skin fibroblasts (of early passage) from the patient had normal levels of activity for the three sulfatases. One week after the first examination, the activities of the three sulfatases in the fibroblasts of the patient declined and within a month were 4%-29% of normal. Total urinary glycosaminoglycans were within normal range. However, further examination showed an increase in the concentration of heparan sulfate, which comprised more than 50% of the total, compared with less than 20% in normal controls. Urinary sulfatides, cholesterol esters, cholesterol, and triglycerides were increased. The results from the study of this unique case of MSD suggest that time-dependent changes affect the activities of sulfatases in MSD. These results also demonstrate the necessity of assaying the sulfatases in both lymphocytes and fibroblasts from suspected cases of MSD. PMID- 2903055 TI - Guillain-Barre syndrome and serum activities of gamma-glutamyltransferase and glutamic-pyruvic transaminase. AB - Objective laboratory indicators of alcohol consumption (mean corpuscular volume and serum glutamic-pyruvic transaminase (GPT), glutamyltransferase (gamma-GT), and glutamic-oxaloacetic transaminase (GOT] were measured in 18 patients with Guillain-Barre syndrome (GBS) and 710 control patients. All of the indicators examined were more frequently found to be pathological in GBS patients, reaching significance for gamma-GT and GPT. Some explanations for this result are discussed. It is concluded that alcohol consumption may be a risk factor for GBS. PMID- 2903056 TI - An evaluation of predisposing factors for testis cancer in Ireland. AB - All testis cancer in Ireland (1980-1985) was analysed (n = 240). Incidence was highest in young adults (5.8/10(5)/year in those aged 25-34 years) with a moderate level in the elderly (1.8/10(5)/year in those over 75 years). Associations elsewhere with maldescent and social class were confirmed but cryptorchidism (12%) was more common than expected. Significant infertility was not identified. Associations with urban domicile (77%, p = 0.001), mental handicap (2.8%, p less than 0.05), recent vasectomy (1.2%, p = 0.009) and certain occupations were observed. PMID- 2903057 TI - On the safety of perioperative adjuvant chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil in breast cancer. AB - Combination cytotoxic chemotherapy (intravenous cyclophosphamide, methotrexate and 5-fluorouracil) was administered within 36 h of mastectomy to 1629 eligible women with operable breast cancer in a randomized controlled clinical trial. Previously reported unpredictable and severe toxic effects were probably due to an interaction between methotrexate and nitrous oxide used in anesthesia. The addition of intravenous 5-formyl-tetrahydrofolate (Leucovorin) and intensification of postoperative monitoring of patients have decreased toxic effects and enhanced the safety of the chemotherapy regimen. PMID- 2903058 TI - Patients, prescribing, and benzodiazepines. AB - In order to establish the current status of benzodiazepine prescribing and also to assess patients' attitudes towards the use of these drugs, we interviewed 450 consecutive patients in 16 community pharmacies about their use of benzodiazepines. Prescribing rates increased ten-fold from the age of 20 to 70 years and were higher in women than in men. The average dose used in the elderly seemed excessive and the choice of hypnotic often inappropriate. The median duration of benzodiazepine use was 2.5 years (range 0-25) and 66% of the patients had been taking benzodiazepines for one year or more. Most of the patients (97%) found the drugs effective in the treatment of anxiety or insomnia. Twenty-two percent took a lower dose than prescribed and 7.5% a higher dose. These data suggest that benzodiazepines are prescribed for excessively long periods and that greater caution is needed in prescribing benzodiazepines for older patients. PMID- 2903060 TI - Decrease of recurrent and feed-forward inhibitions under high pressure of helium in rat hippocampal slices. AB - The effect of high helium pressure on inhibitory synaptic transmission was studied in rat hippocampal slices with extracellular recordings. Both feed forward and recurrent GABAergic inhibition were tested in the CA1 region with paired-pulse stimulation paradigms. The efficiency of both types of inhibition decreased under high pressure (80 atm). However, the depression of synaptic and antidromic field potentials induced by perfusion of GABA or muscimol were not significantly affected by pressure. High pressure induced hyperexcitability of CA1 pyramidal cells. This effect was reduced by the application of 2 aminophosphonovalerate or GABA. The present results suggest that: (1) high pressure reduces the efficiency of the GABAergic inhibitory transmission but does not affect the sensitivity of GABAA receptors; (2) two different processes (reduction of GABAergic inhibition and facilitation of N-methyl-D-aspartate mediated excitation) might be a direct consequence of the change in the voltage sensitive ion channels under high pressure and might be involved in the development of the pressure-induced hyperexcitability of CA1 pyramidal cells. PMID- 2903059 TI - Comparison of the central and peripheral effects of cetirizine and terfenadine. AB - The peripheral and central effects of 10 mg cetirizine 2 HCl and 60 mg terfenadine have been compared with placebo in 9 healthy male volunteers. The peripheral effect, in terms of cutaneous reactivity to 1 microgram histamine i.d., was measured by planimetry of the wheal and erythemas. Central effects were assessed with a self-evaluation visual scale and from the results of electroencephalographic spectrum analysis. Peripheral inhibition of histamine reactivity was more intense and quicker for cetirizine than for terfenadine. On the self-evaluation scale, no significant difference between terfenadine, cetirizine and placebo was noted. The quantified EEG did not show any variation in spectral parameters at any time after cetirizine. By contrast, at 6 h terfenadine had increased slow waves and had inhibited the alpha band. Thus, 10 mg cetirizine 2 HCl had less effect on the central nervous system than terfenadine 60 mg, whilst its peripheral action appeared more quickly and was more intense. PMID- 2903061 TI - Behavioral classification of excitatory amino acid receptors in mouse spinal cord. AB - Intrathecal injections of excitatory amino acid (EAA) agonists to the spinal cord of mice produces behavioral activation manifest as biting and scratching of the hindquarters. The dose-response relationship of EAA (N-methyl-D-aspartate (NMDA), kainate, quisqualate and glutamate)-induced activation revealed qualitative and quantitative differences in their pattern of action, suggesting that these agonists act at distinct receptors. Evaluation of the blockade of EAA-induced bites by a series of antagonists: DL-2-amino-5-phosphonovalerate (APV), gamma-D glutamyl glycine (DGG), kynurenate and glutamylaminomethylsulphonate (GAMS), indicated that selective activation of the NMDA, quisqualate and kainate receptors can be demonstrated using this behavior. The NMDA receptors could be subdivided on the basis of different sensitivity to kynurenate and APV. Antagonist-resistant components of both kainate and quisqualate action were also shown. Thus, the biting behavior induced by the administration of intrathecal EAA agonists can be used as a relatively selective behavioral tool for assessing the pharmacological profile of action of excitatory amino acid agonists and antagonists in the spinal cord. PMID- 2903063 TI - Activation of the A10 mesolimbic system by the sigma-receptor agonist (+)SKF 10,047 can be blocked by rimcazole, a novel putative antipsychotic. AB - This study evaluated with electrophysiological and behavioral techniques the ability of rimcazole, a novel putative antipsychotic and selective sigma-receptor ligand, to antagonize the stimulation of the mesocorticolimbic dopamine system by the sigma-agonist, (+)SKF 10,047. Rimcazole effectively blocked the (+)SKF 10,047 induced excitation of ventral tegmental dopamine neurons while having no effect on either spontaneous activity or apomorphine-elicited slowing of A10 firing. Rimcazole also antagonized the behavioral hyperactivity produced by (+)SKF 10,047, but not by d-amphetamine which is also mediated through the same mesolimbic dopamine pathway. These data provide further evidence that rimcazole's novel pharmacologic profile may involve a blockade of sigma-receptors on mesocorticolimbic dopamine neurons. PMID- 2903062 TI - Alpha-adrenoceptor occupancy by N,N-dimethyl-2-bromo-2-phenethylamine hydrobromide (DMPEA) in rat vas deferens. AB - The effects of N,N-dimethyl-2-bromo-2-phenethylamine hydrobromide (DMPEA) on alpha 1- and alpha 2-adrenoceptors were examined in the isolated rat vas deferens. The active species of DMPEA was the corresponding ethyleniminium ion, which forms in the biophase, since pretreatment of tissues with sodium thiosulphate completely prevented the DMPEA-induced inhibition at alpha 1- and alpha 2-adrenoceptors. DMPEA was approximately 42-fold more potent in inhibiting alpha 2-adrenoceptors than it was in inhibiting alpha 1-adrenoceptors. The antagonism of both receptor types was reversible since washing of the tissues after incubation with DMPEA brought the agonist dose-response curve back to the control value. At alpha 1-adrenoceptors, DMPEA displaced the noradrenaline dose response curve to the right and concomitantly depressed the maximum response, effects which are consistent with a non-competitive mechanism of action. At alpha 2-adrenoceptors, DMPEA caused a parallel shift of the clonidine or noradrenaline dose-response curve to the right in field-stimulated prostatic portions of the rat vas deferens. The antagonism appeared to be competitive at low concentrations, whereas the shift of the clonidine dose-response curve at higher concentrations became overproportional to the DMPEA concentration. A combination of DMPEA with idazoxan produced a less-than-additive shift of the dose-response curve for clonidine, indicating that these antagonists do not bind to the same site. PMID- 2903064 TI - Tetrahydroaminoacridine selectively attenuates NMDA receptor-mediated neurotoxicity. AB - Addition of the acetylcholinesterase inhibitor 1,2,3,4-tetra-9-hydroaminoacridine (THA) at 1-3 mM markedly reduced the neuronal cell loss that otherwise followed brief exposure of murine cortical cell cultures to 500 microM N-methyl-D aspartate (NMDA). This novel antagonism was selective for NMDA receptor-mediated toxicity, as it extended to glutamate toxicity but not to quisqualate toxicity, and was THA concentration-dependent between 100 microM and 3 mM, with IC50 approximately 500 microM. The antagonism was probably not due to enhancement of endogenous cholinergic action, as it was not mimicked by acetylcholine, carbachol, or bethanechol; rather, it likely reflected a recently described interaction of THA with the phencyclidine receptor. Exploration of structural specificity revealed some partial neuron-protection with high concentrations of other cholinesterase inhibitors--physostigmine, neostigmine, and edrophonium, but not the structurally related potassium channel blocker, 4-aminopyridine. Further examination of correlations between THA-like structure, and neuron-protective activity, may provide useful insights in the development of new antagonists of NMDA receptor-mediated neurotoxicity. PMID- 2903065 TI - Antibody level of New Zealand children immunized with the triple vaccine DTP (diphtheria-tetanus-pertussis). AB - Enzyme-linked immunosorbent assay (ELISA) tests were used to measure IgG antibody levels in 2638 New Zealand children who had been immunized with the triple vaccine DTP. The percentage of children immune to diphtheria decreased with age. The percentage of children immune to tetanus varied from 67.1 to 55.0%. The percentage of children with measurable antibody to pertussis increased with age. The mean percentages of children with measurable antibody or immunity to one or more DTP components were 34.2% (with 3 components), 34.4% (2 components), and 78.1% (1 component). It appears the immunization strategy for diphtheria and tetanus is satisfactory for herd immunity in New Zealand children. However, the current pertussis strategy may not be providing adequate immunity to 5-year-olds in this country. PMID- 2903067 TI - Ultrastructure of spinal cord grafts with and without cografts of locus coeruleus in oculo. AB - The ultrastructure of spinal cord and spinal cord-locus coeruleus double grafts transplanted to the anterior chamber of the eye of adult rats was studied. The present results show that single spinal cord grafts express several morphologically organotypical characteristics of normal spinal cord at the ultrastructural level. Thus, the parenchyma was divided into a cell-rich layer corresponding to the normal gray matter and an axonal layer with a large amount of myelinated fibers and immature oligodendrocytes. In the cellular layer, a variety of cell types of different sizes were observed. The neurons had different patterns of cytoplasmic organelles, including Nissl bodies, Golgi apparatus, mitochondria, and polysomes. The Nissl substance was variable and some neurons appeared to be immature. Although the spinal cord grafts are in a state of relative gliosis, surrounded by a glial barrier, cografted fetal locus coeruleus catecholamine neurons are able to innervate the spinal cord grafts and form anatomically relevant synapses with the spinal cord neuronal elements as revealed by TH-immunoelectron microscopy. In conclusion, several organotypical features of normal spinal cord are found. Examples also were found, however, of a disturbed and delayed development that have to be considered when evaluating the functional potential of grafted cells. PMID- 2903066 TI - Binding of the beta-blockers timolol and H 216/44 to ocular melanin. AB - The eyes from pigmented rabbits were instilled with the beta-adrenoceptor antagonists H 216/44 or timolol. After a single instillation (1.9 mumol), the iris and ciliary body contained H 216/44, which decreased with a half-life of approx. 43 days. Daily instillation caused a gradual increase in the content of H 216/44 and timolol in the iris and ciliary body, the steady-state concentration of timolol being 10 times higher than that of H 216/44. The concentrations of H 216/44 were seven times higher in the iris and ciliary body of pigmented rabbits than in albino animals. H 216/44 was reversibly bound to the melanosomes from the iris and ciliary body and not metabolized in this tissue. In vitro binding of timolol and H 216/44 to bovine melanosomes showed comparable multi-site binding curves. The binding of chlorpromazine was substantially higher. The beta-blockers could be more readily released from the melanosomes with aqueous solutions of salt and ethanol than with distilled water. It is concluded that both H 216/44 and timolol bind reversibly to ocular melanin. The differences in binding characteristics in vitro may only partly explain the differences in the in vivo binding to ocular melanin in the rabbit eye. PMID- 2903068 TI - Adrenal medullary autografts into the basal ganglia of Cebus monkeys: injury induced regeneration. AB - Questions arising from recent clinical neural transplantation trials in Parkinson's disease have under-scored the necessity for a thorough experimental evaluation of the structural and functional consequences of this procedure. The present study investigated the neuroanatomical host reaction to intrastriatal implants in normal and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) treated nonhuman primates. Nine monkeys (Cebus apella) received intrastriatal implants using either a stereotactic approach with a silver tissue carrier or an open microsurgical procedure. Seven of these animals received intrastriatal adrenal medullary autografts, while two received control implants consisting of the tissue carrier alone. One month following transplantation, the hosts' brains were evaluated via immunohistochemical and routine histologic methods. In both MPTP-treated and normal monkeys, enhanced ipsilateral expression of tyrosine hydroxylase-like immunoreactive (TH-IR) fibers in the caudate nucleus was observed, despite minimal survival of adrenal chromaffin cells in the implants. The intensity of this response was greatest adjacent to the implant site, but a clearly increased degree of ipsilateral striatal fiber staining also could be seen several millimeters from the graft. TH-IR fibers also were more dense and of thicker caliber throughout the nigrostriatal and mesolimbic pathways ipsilateral to the implant. Control stereotactic implants, consisting of a silver tissue carrier alone, produced a similar enhancement of immunoreactive fibers, suggesting an induction of TH-IR fibers by the parenchymal injury produced during surgical implantation. There are two major hypotheses proposed to explain why adrenal medullary grafts may promote functional recovery in human parkinsonism: (1) replacement of lost striatal neurotransmitter (dopamine) by the viable grafted tissue, or (2) induction of recovery of remaining host dopaminergic systems by the implantation procedure. Our current data appear to support the latter. PMID- 2903069 TI - In vitro enhancement of human platelet aggregation by somatostatin. AB - Very low concentrations of somatostatin (S-14) strongly potentiate the in vitro aggregation induced by collagen, ristocetin and arachidonic acid, but not that induced by ADP or epinephrine, in both human platelet rich plasmas and gel filtered platelet preparations. Desensitization phenomena may be induced either by repeated addition of S-14 or long lasting contact between S-14 and platelets. PMID- 2903070 TI - Isolation of less than Glu-Gly-Leu-Arg-Trp-NH2 (Antho-RWamide II), a novel neuropeptide from sea anemones. AB - Using a radioimmunoassay for the peptide sequence Arg-Phe-NH2 (RFamide), a novel peptide has been purified from acetic acid extracts of the sea anemone Anthopleura elegantissima. This peptide has the structure less than Glu-Gly-Leu Arg-Trp-NH2, and was named Antho-RWamide II. Antho-RWamide II is a neuropeptide. Its structure is closely related to an earlier characterized neuropeptide from Anthopleura less than Glu-Ser-Leu-Arg-Trp-NH2 (Antho-RWamide I). PMID- 2903071 TI - The primary structure of the 70 kDa subunit of bovine soluble guanylate cyclase. AB - The primary structure of the 70 kDa subunit of soluble bovine guanylate cyclase, which catalyzes the formation of cyclic GMP from GTP, has been determined. The alignment of six different clones out of two bovine libraries yielded a total of 3.1 kb with a coding region of 1857 bases. The open reading frame encodes a protein of 619 amino acids and a molecular mass of 70.5 kDa. Antibodies raised against a synthetic peptide, which corresponded to the C-terminus of the deduced sequence precipitated guanylate cyclase activity from guanylate cyclase-enriched preparations. PMID- 2903072 TI - Expression of K channels in Xenopus laevis oocytes injected with poly(A+) mRNA from the insulin-secreting beta-cell line, HIT T15. AB - Two types of exogenous K channel were identified in Xenopus laevis oocytes injected with poly(A+) mRNA from the insulin-secreting cell line HIT T15. One of these was the ATP-regulated K channel (G channel) as evidenced by its conductance and inhibition by tolbutamide. The other resembled the Ca-activated K channel from beta-cells. PMID- 2903073 TI - GTP modulates calcium binding and cation-induced conformational changes in erythrocyte transglutaminase. AB - Calcium binding to erythrocyte transglutaminase was determined by equilibrium dialysis. Results indicate that 6 ions are bound to the enzyme both in the absence and in the presence of GTP and that the nucleotide reduces the affinity of the enzyme for calcium. Furthermore, I- fluorescence quenching and proteolytic inactivation experiments proved that GTP also alters the conformation of the enzyme. It is thus suggested that multiple mechanisms are involved in the regulation of the enzyme activity by GTP. PMID- 2903075 TI - [Occupational law violations of paramedical personnel and their prevention (1)]. PMID- 2903074 TI - Assignment of the human aminopeptidase N (peptidase E) gene to chromosome 15q13 qter. AB - The gene for aminopeptidase N (EC 3.4.11.2) has been located on the human chromosome 15q13-qter using HindIII-cleaved DNA from a panel of hybrids between rodent and human cells. The Southern blots were probed by the 5'-EcoRI fragment of the recently cloned human aminopeptidase N cDNA. PMID- 2903076 TI - [Results and prospectives of the first year of study of the mechanism of neurohumoral regulation of the functions of the visceral systems]. PMID- 2903077 TI - Recognizing and treating fears in general practice. AB - Recognizing and treating dental fears requires attention to the behavioral, physiologic, and cognitive manifestations of anxiety. This article provides questions to ask and strategies to employ to identify and use in assisting the fearful patient in general practice. PMID- 2903078 TI - Characteristics of cyclic AMP enhancement of retinoic acid induction of increased transglutaminase activity in HL60 cells. AB - When the human myeloid leukemia cell line (HL60) is induced to differentiate with retinoic acid (RA), there is a concentration-dependent increase in transglutaminase (TGase) activity which peaks on day 5. While dibutyryl 3',5' cyclic adenosine monophosphate (db-cAMP) alone produced only a slight increase in TGase activity in HL60 cells, the concomitant addition of db-cAMP (100 microM) with RA (10(-12)-10(-4) M) potentiates RA induction of TGase activity. Maximal increases in TGase activity (2- to 10-fold) were observed with 10(-4)-10(-7) M RA and when db-cAMP was present from 24 to 48 h after the addition of RA. The cyclic nucleotide enhancement was dose-dependent from 10 to 100 microM of cAMP. Less marked increases were observed with 8-bromo-cAMP and with the phosphodiesterase inhibitor theophylline. Although the simultaneous addition of PGE1 or PGE2 (10( 8)-10(-6) M) produced no enhancement of RA-induced TGase activity, adding PGE1 or PGE2 24 or 48 h following RA treatments produced an enhancement of TGase activity. The phosphodiesterase inhibitor potentiated the increases produced by db-cAMP and the prostaglandins. Dibutyryl cAMP enhanced the ability of RA to induce the cells to reduce nitroblue tetrazolium (NBT), a functional measure of differentiation, at lower concentrations of RA and with shorter treatment durations. cAMP potentiates RA-induced TGase activity in HL60 cells and the combination appears to be associated with enhanced RA-induced differentiation. PMID- 2903079 TI - Characteristics of changes in blood circulation induced by cold stimulation in pre-eclamptic women. AB - Changes in peripheral deep body temperature (p-DBT) after cooling were examined in normal, chronically hypertensive pregnant and pre-eclamptic subjects. The recovery of p-DBT after cooling was delayed significantly in the pre-eclamptic subjects, as compared to findings in the other two groups. The delay in the recovery process of blood flow in the tissue after cooling, probably due to disturbance of the vasodilating process, is a characteristic of microcirculation in pre-eclamptic subjects. PMID- 2903080 TI - Effect of mode of delivery on incidence of respiratory distress syndrome. AB - The effect of route of delivery on incidence of respiratory distress syndrome (RDS) has been controversial. While some investigators have reported no difference in RDS rates in infants born by cesarean section as compared to vaginal delivery, others have shown a significant increase in risk for RDS among infants born by cesarean section. Data from the 297 patients comprising the placebo group in the recently completed collaborative study of antenatal steroid therapy in the prevention of neonatal RDS, were analyzed to determine the effect of mode of delivery on RDS. The results indicate that infants born by cesarean section without labor have a higher risk for neonatal RDS than infants born vaginally or by cesarean section after a trial of labor. PMID- 2903081 TI - Characteristics of maternal deaths following cesarean section in a developing country. AB - A retrospective analysis was made of 27 maternal deaths after cesarean section occurring over a 5-year period. Sepsis was the single most important cause of maternal death (81.5%). The commonest indications for the cesarean sections were obstructed labor (59.3%) and cord prolapse (18.5%). The causes of maternal deaths were classified as avoidable and recommendations were made for their prevention. PMID- 2903082 TI - Sexually transmitted diseases in women with urethral syndrome. AB - Frequency of micturition and dysuria were prominent symptoms in 135 (57%) of 237 women with urethral syndrome. Ureaplasma urealyticum, Mycoplasma hominis and Chlamydia trachomatis were the principal organisms associated with the urethral syndrome (38.41%, 28.14% and 11.11%, respectively). Escherichia coli was cultured from four patients and Herepes genitalis and Neisseria gonorrhoea were isolated from five patients. Infections with more than one organism were frequent. Thirty one of 135 patients were infected by two organisms, 27 by three and 4 patients by four microorganisms. Vaginitis due to Garnerella vaginalis, Candida spp. and Trichomonas vaginalis was discovered in 52 (39%) of 135 patients. PMID- 2903083 TI - Abnormal glucose screening in pregnancy in patients with normal oral glucose tolerance tests as a screening test for fetal macrosomia. AB - Minor abnormalities of carbohydrate metabolism in pregnancy are a risk factor for delivery of a macrosomic infant. However, the 50-g 1-h oral glucose screen at 28 weeks is not a useful screening test for macrosomia in pregnant patients with normal glucose tolerance tests, because a positive screen does not raise the probability of delivering a macrosomic infant sufficiently to warrant intervention. PMID- 2903084 TI - Ultrasound evaluation of amniotic fluid: outcome of pregnancies with severe oligohydramnios. AB - We studied a group of 247 patients out of 7725 patients who had an ultrasonic examination between 32 and 36 weeks gestation and were found to have oligohydramnios (amniotic fluid volume (AFV) less than or equal to 2.0 cm). We compared the features of labor and mode of delivery and perinatal outcome in this group with that of a normal control group of 247 patients who also had an ultrasonic examination between 32 and 36 weeks gestation and were found to have normal AFV (greater than 2.0 to less than 8.0 cm). The incidence of induction of labor, of elective cesarean section, of preterm delivery (less than 37 weeks' gestation) was significantly higher in the oligohydramnios group (study group) as compared with the incidence in the control group (P less than 0.05). The incidence of fetal distress in antenatal and intrapartum period, pH (less than or equal to 7.2), of low Apgar score (0-5), of intrauterine growth retardation (IUGR) (less than tenth centile) infants, of major fetal anomaly and perinatal mortality rate (PNMR) are significantly higher in the oligohydramnios group as compared with the incidence and PNMR in the normal control group (P less than 0.05). The ultrasonic finding of oligohydramnios should alert the clinician regarding the possibility of problems in labor and perinatal period. PMID- 2903085 TI - Randomised trial comparing combinations of cyclophosphamide and cisplatin without or with doxorubicin or 4'-epi-doxorubicin in the treatment of advanced ovarian cancer. AB - Forty-eight patients with FIGO stage III and IV epithelial carcinomas of the ovary were entered in this randomised trial. Radical surgery was performed and no residual tumor with a diameter greater than 2 cm was left behind. Of these patients 62.5% (10/16) had a complete or partial response on cyclophosphamide + cisplatin (CP) 87.5% (14/16) on cyclophosphamide + doxorubicin + cisplatin (CAP) and cyclophosphamide + 4'-epi-doxorubicin + cisplatin (CEP). The median time to progression was 3.5 months on CP, 12.5 months on CAP and 11.0 months on CEP. Patients treated with CAP combination chemotherapy had generally longer progression-free survival (log rank chi 2 = 5.4; P = 0.04). No significant difference was found, however, between patients on CAP and CEP. The median survival times were 12.5 months on CP, 26.5 months on CAP and 14.0 months on CEP. Patients treated with CAP combination chemotherapy had generally longer survival (logrank chi 2 = 9.08; P = 0.0099). No significant difference was found, however, between patients on CAP and CEP in terms of survival. Asymptomatic mild-to moderate laboratory test toxicity occurred in 6-12% of patients on CP, 6-12% on CAP and no toxicity of this type and grade on CEP. Nausea and vomiting were also less severe and less frequent in the CEP group. Cardiotoxicity was seen in 12.5% (2/16) only in the CAP group. PMID- 2903086 TI - The epidemiology of cancer of the uterine corpus in Canada: 1950-1985. AB - Morbidity and mortality patterns in Canada from malignancies of the corpus uteri, were analyzed for the periods 1970-1980 and 1950-1985, respectively. Although rates of morbidity have fluctuated between 15.0 and 19.6 new cases per 100,000 population per year, age-specific rates for women aged 35-44 have declined significantly (0.26 fewer new cases per 100,000 population per year; P less than 0.05). Mortality rates have declined by approximately 50% between 1950 and 1985 (P less than 0.0001) with age-specific rates for women aged 35-44, 45-54, 55-64, 65-74 and 75-84 also exhibiting significant declines (P less than 0.02). PMID- 2903087 TI - The value of computed tomography in staging cervical carcinoma. AB - The purpose of our study was to determine the value of computed tomography (CT) in relation to the local extension of cervical carcinoma and the possible spread in the peritoneal and the retroperitoneal space. Sixty-five patients treated for cervical carcinoma during the period 1980-1986 were included in the study. Histologic diagnosis of the disease was done by punch cervical biopsy and diagnostic curettage. The investigation of all patients included intravenous pyelography, barium enema, bone and liver scanning and CT. Our results demonstrate a correlation between CT and pathologic data in 75-78.5% depending on stage. CT may be considered as a dependable method for staging of cervical carcinoma. PMID- 2903088 TI - Adrenal response to adrenocorticotropin stimulation in unexplained infertile women. AB - The response to a rapid intravenous administration of adrenocorticotropin (ACTH, cortrosyn) was compared in 24 unexplained infertile women and 13 fertile women. There was no significant difference in the response to a rapid ACTH stimulation as expressed by the slope of testosterone (T) response in both groups. However, the individual and mean T values prior and following the stimulation were significantly higher in the infertile group (P less than 0.001; P less than 0.005, respectively). There was no significant difference in individual values as well as in mean basal values or in mean values of 17-hydroxyprogesterone (17-OHP) after the stimulation between the two study groups (P less than 0.3; P less than 0.9, respectively). There was no significant difference in individual values as well as in mean values of dehydroepiadnrosterone (DHEA) before or 90 min after the stimulation between the two study groups (P less than 0.1; P less than 0.2, respectively). It can therefore be concluded that the elevated basal testosterone values in the infertile group originated from the ovary. Despite the fact that no attempt was made to reduce androgen values 7 (46.66%) of 15 infertile women who were available for follow-up and treatment conceived following ovulation induction therapy. PMID- 2903089 TI - Clearance pattern of maternal serum pregnancy specific beta 1-glycoprotein after treatment in active and regressed tubal pregnancy. AB - The clearance pattern of maternal serum pregnancy specific beta 1-glycoprotein (SP1) was studied in 16 cases of tubal pregnancy (9 active and 7 regressed) after 12, 24, 48, 72, 96, 120 and 192 h following surgery. The mean values of the hormone in both groups showed a statistically highly significant difference in all measurements before and after treatment (P less than 0.001), but they followed the same exponential regression pattern. The half-life of SP1 in active tubal pregnancies after salpingectomy was 36.2 h and in regressed tubal pregnancies after salpingostomy was 37.5 h. PMID- 2903090 TI - Ultrasonic assessment of ovulation in cyclofenil induced ovulatory cycles. AB - Graafian follicle growth was studied by ultrasound scanning during the peri ovulatory period in 64 ovulatory cycles in 32 infertile patients on cyclofenil treatment, and compared with a control group of 32 patients with confirmed ovulatory cycles assessed on the basis of serum progesterone levels in the middle of the second half of the cycle. The mean maximum diameters of the leading follicles before ovulation were 21.9 +/- 0.6 (S.E.) mm and 24.4 +/- 0.5 (S.E.) mm, respectively for the cyclofenil group and the normal control group (P greater than 0.05). In 79% of the cyclofenil stimulated group and 83% of the spontaneous ovulation group, ultrasonic evidence of ovulation was present between 12 and 36 h after the initial increase in urine LH levels. Ultrasound scanning was found to be simple, and a quick method of monitoring graafian follicle development and ovulation on cyclofenil therapy and the cycles were comparable to the spontaneous ovulatory cycles as assessed on the basis of graafian follicle diameter, and the time of ovulation. Cervical score was not found to be useful to assess ovulation time in the cyclofenil treated group since 31.3% achieved a score of 10 or more on day -4, 93.8% within 24 h of ovulation and 24% on day 3 following the ovulation. PMID- 2903091 TI - Ultrastructure of endosalpingeal biopsies in infertile patients: correlation with reproductive success. AB - We calculated the percentage of ciliated cells (PCC) in salpingeal microbiopsies of 41 patients with tubal infertility and ampullary microbiopsies of 36 fertile women, using the planimetric method at 500-1000 x at the scanning electron microscope. No relation was found between PCC and fertility after surgery. Thus normal ciliation does not seem to be essential for reproductive success and other factors such as the state of preservation of the tubal wall may be important. PMID- 2903092 TI - Ectopic pregnancy without laparotomy: defining the incidence of manageable patients. AB - To assess the incidence of ectopic pregnancies meeting published criteria for laparoscopic or medical therapy, we retrospectively evaluated tubal pregnancies admitted during a 12-month period. Because 41/121 (34%) were visible laparoscopically, unruptured, and less than or equal to 3 centimeters in diameter, we conclude that substantial numbers of ectopics may be managed without laparotomy. PMID- 2903093 TI - Ovarian function after the menarche and hormonal contraception. AB - The aim of the study was to determine the date of regular ovulation after the menarche to better understand the physiology of female adolescence, especially as it pertains to the use of hormonal contraception. Early morning urine samples were collected from 51 girls in the perimenarche for 9 weeks semi-annually during 2 years. Estrone- and pregnanediol-3-glucuronide values were determined. Cycles lasting 35-40 days at the onset of menses shortened to 28 days after the 23rd 25th cycle. Menses reached a 5.0-5.5 day average length at about the same time. After the 20th cycle, ovulation could be demonstrated in more than 50% of the study patients. Using a scoring system, regular ovulation could be expected on the basis of somatic data with scores of greater than 16. Hormonal contraception may be prescribed 2 years after the menarche, based on scores of greater than 16 and ovulation proven be hormonal cytology and basal body temperature. PMID- 2903094 TI - Analysis of sterilization failure in Brazil. AB - A study of 13,423 female sterilization procedures performed from 1981 to 1984 in Rio de Janeiro, Brazil, was conducted to determine the level of sterilization failure. The lifetable cumulative failure rate was 0.54 at 12 months per 100 initial sterilizations, increasing to 1.04 at 48 months. Results of a multivariate analysis indicated that the differential in the rate of sterilization failure by woman's age at sterilization at 12 and 24 months was statistically highly significant. However, the differential rate of failure by the other variables such as whether sterilized during a training period, number of sterilizations per surgeon per day, and year of sterilization were not statistically significant. PMID- 2903095 TI - Menstrual regulation in Bangladesh: an evaluation of training and service programs. AB - This article evaluates the performance of three urban menstrual regulation (MR) training and service programs in Bangladesh. Virtually all of the MR providers including physicians and paramedics in the three centers received training in various MR procedures by means of demonstration or class lectures. However, a significant proportion of the trained MR providers were unable to render proper MR services due to the lack of clinical facilities and lack of equipment. Analysis of follow-up data for MR clients revealed that those women who utilized MR procedures offered through the centers had an average of about three live births. Physician providers were more likely to serve clients from a higher socioeconomic strata, while paramedical providers were more likely to serve MR clients from lower socioeconomic strata or agricultural background. Most of the clients receiving MR services were ever and current users of contraceptives and developed fewer complications from MR procedures than those served by untrained traditional herbalists, healers or birth attendants. PMID- 2903096 TI - Hyperprolactinemic infertile men. AB - Clinical descriptions of prolactin in states of oversecretion are presented in 49 patients that presented for infertility investigation. Radiological assessment did not reveal microadenomas in these patients. Erectile dysfunction or deficient semen parameters could be early manifestations of hyperprolactinemia in some infertile men. PMID- 2903097 TI - Pregnancy after hemipelvectomy: a case report and review of the literature. AB - Hemipelvectomy is a most radical attempt at cure of malignant tumors of the pelvis and the upper portion of the femur. Pregnancy following this severely mutilating operation is rare. Despite the considerable loss of pelvic support patients do remarkably well. A case of pregnancy following hemipelvectomy is presented and represents the 16th report in the English literature. The anatomic consequences of hemipelvectomy are described and a review of the past 61 years experience with pregnancy following this operation is presented. PMID- 2903098 TI - Occult infiltrating placenta previa percreta: an unusual case highlighting the management problems in a young patient. AB - Placenta previa in association with placenta accreta has been recorded on average in 1 in 500 pregnancies; its association with placenta percreta is a much rarer condition. We report an unusual case of placenta previa which presented as a severe form of occult parasitic infiltration, invading the internal iliac vessels. This was followed by life-threatening complications, despite preventative measures. Use of a prediction index to suspect placenta previa is mentioned. PMID- 2903100 TI - The advantages and disadvantages of subspecialization. AB - Writing as a subspecialist I intend to show: (1) that subspecialization is as necessary in developing countries as it is in developed countries; (2) that there are universal principles of human nature likely to govern the process of subspecialization, independently of a country's political system or health care policies; and (3) that the pyramidal system of tertiary referrals to subspecialists is threatening to price doctors out of many people's reach. PMID- 2903099 TI - Recurrent uterine myomata in three sisters--an uncommon occurrence. AB - Three sisters who developed recurrent uterine myomata from a very young age are presented. Despite repeated attempts at myomectomy, all three cases had hysterectomies ultimately. Complications encountered during surgery were severe hemorrhage, inadvertent injury to bladder and bowel in two patients and a rare complication of colonic-uteric-cutaneous fistula occurring post-operatively in one patient. Histology of the final hysterectomy specimens in two cases showed low grade leiomyosarcoma and cellular myoma, respectively. PMID- 2903101 TI - Molecular genetic studies on alcohol and aldehyde dehydrogenase: individual variation, gene mapping and analysis of regulation. PMID- 2903102 TI - Molecular genetics of alcohol-metabolizing enzymes. PMID- 2903103 TI - Effects of oestrogen on the expression of a 4.4 kb mRNA in the ZR-75-1 human breast cancer cell line. AB - A cDNA library has been constructed from the poly(A)+ mRNA of oestrogen stimulated ZR-75-1 human breast cancer cells. Screening by differential hybridization has identified eight clones which are stimulated between 4- and 16 fold by oestrogen. Two clones (pLIV-1) that are stimulated 4-fold, hybridize to three different mRNA species. A further five recombinants encode for a mRNA 600 bp long which is induced greater than 16-fold and have been shown to cross hybridize to the oestrogen-responsive clone, pS2, isolated from the MCF-7 breast cancer cell line. Oestradiol was shown to be without detectable effect upon the expression of mRNA for dihydrofolate reductase, which is reported to be oestrogen regulated in MCF-7 cells. Actin gene expression is also unresponsive to oestradiol in ZR-75-1 cells. These results suggest that pLIV-1 represents a previously unidentified mRNA that may be involved in the oestrogen-regulated growth of ZR-75-1 human breast cancer cells. PMID- 2903104 TI - Immunocytochemical analysis of the regeneration of myofibrils in long-term cultures of adult cardiomyocytes of the rat. AB - Dissociated adult rat ventricular cardiomyocytes obtained from hearts by retrograde perfusion with collagenase were investigated in long-term cultures. Myofibril regeneration, isoprotein transition of alpha- and beta-myosin heavy chain (MHC), and M-band localization of M-creatine kinase in the reconstituting heart cells were studied. Myofibril formation was demonstrated by the use of antibodies against either cardiac C-protein or myomesin as early differentiation markers. Four days after plating, small myofibrils could be identified in attached cells in a perinuclear fashion; later in culture the cells displayed various shapes and myofibril distribution. Frequently a patchy distribution of myofibrils within the extending peripheral processes could be observed. Colocalization of sarcomeres and phalloidin-stained F-actin filament bundles was demonstrated by double fluorescence staining and by the use of high intensifying video microscopy and computerized image processing. The immunofluorescence distribution of alpha- and beta-MHC isoproteins in newly isolated and cultured cardiomyocytes changed from 100% alpha-MHC and 70% beta-MHC in rod-shaped cells to about 100% beta-MHC and 70% alpha-MHC in spread out cultured cells. This shift was corroborated by a relative gradual decline in alpha-MHC at the expense of increasing amounts of beta-MHC with time in culture as assessed by sodium dodecyl sulfate gel electrophoresis of total cell homogenates. In addition, whereas rod shaped newly isolated cardiomyocytes showed a clear M-band association of M creatine kinase as found in adult heart tissue, adult cultivated spread out cells did not show a cross-striated pattern after incubation with antibody. Taken together, these observations suggest that adult cardiomyocytes not only undergo extensive morphological transitions in long-term cultures, but also generate new myofibrillar structures lacking M-creatine kinase and containing the beta-MHC, thus fitting the characteristics of fetal myofibrils. These results indicate a change from the adult terminally differentiated to a less differentiated state of the cardiac cells in culture. PMID- 2903105 TI - Cyclosporin-induced remission of IDDM after early intervention. Association of 1 yr of cyclosporin treatment with enhanced insulin secretion. The Canadian European Randomized Control Trial Group. AB - A randomized double-blind placebo-controlled trial was undertaken to determine whether cyclosporin enhances remission of insulin-dependent diabetes mellitus (IDDM) through the 1st yr after diagnosis. Dosage with insulin was minimized with target control of blood glucose levels less than or equal to 7.8 mM (140 mg/dl) before meals. Metabolic control was evaluated by serial determinations of glycosylated hemoglobin levels, and endogenous secretion of insulin was evaluated by determination of the levels of glucagon-stimulated insulin-connecting peptide (CP) in the plasma at 3-mo intervals. A compound definition of remission required a glucagon-stimulated CP level in plasma greater than or equal to 0.6 nM or a non insulin-receiving state (NIR) in which target control of glycemia was maintained without administration of insulin. A clinical definition of remission required only the NIR state as defined. One hundred eighty-eight patients aged 10-35 yr entered the study within 6 wk of initiation of insulin therapy and within 14 wk of onset of symptoms and were studied for 1 yr. There were no significant differences in metabolic control between the two treatment groups during the study. The anticipated adverse effects of cyclosporin were not more frequent or severe than in other experience with the drug, but histological changes attributable to cyclosporin were present in some kidney biopsies obtained from selected patients after 1 yr. At 1 yr, by the compound definition, 33% of the cyclosporin-group and 21% of the placebo-group patients were in remission, when the corresponding rates for NIR remissions were 24 and 10%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903107 TI - [Myocardial revascularization using both internal mammary arteries. Clinical results and surgical strategy]. AB - To improve the benefits from coronary artery grafting with internal mammary artery (IMA) several technical manoeuvres and methods have been developed to increase the number of coronary arteries and their branches that can be bypassed with internal mammary arteries. Between November 1985 and December 1986, 50 patients underwent a surgical myocardial revascularization procedure using both internal mammary arteries by single or sequential anastomoses and supplemental saphenous vein graft. In 42% of these patients complete revascularization was achieved employing only internal mammary artery grafts. One hundred and twenty six internal mammary artery grafts (77% of the total coronary bypass performed), were placed. One patient developed perioperative myocardial infarction. Reparative surgery to control immediate post-operative bleeding was required in two patients. Post-operative coronary angiography performed in 30 patients showed all patent internal mammary artery grafts but one. No late deaths occurred. Mean follow-up of 10 months was complete in 50 patients, of whom 94% are symptom free. We conclude that bilateral internal mammary artery grafting can be performed with low operative risk and can provide excellent long-term functional improvement and survival employing only high patency arterial conduit. Moreover, it doesn't significantly increase surgical morbidity. PMID- 2903106 TI - Intracellular location of the multidomain protein CAD in mammalian cells. AB - The first three steps of mammalian de novo pyrimidine biosynthesis are catalyzed by the multifunctional protein CAD, consisting of glutamine-dependent carbamylphosphate synthetase, aspartate transcarbamylase, and dihydroorotase. The intracellular distribution of CAD in two hamster cell lines, BHK 21 and BHK 165 23 (a strain in which the CAD gene was selectively amplified), was determined by differential centrifugation and by two different cytochemical immunolocalization methods. Ammonia-dependent carbamylphosphate synthetase I was found in both cell types at a concentration of 0.01% of the total cell protein, so its distribution was also determined as a control for possible cross-reactivity of the CAD antibody probes and as a mitochondrial marker. CAD was localized in the cytoplasmic compartment and almost completely excluded from the nucleus. A punctate staining pattern suggested that it was not uniformly dispersed throughout the cytosol (unlike typical soluble proteins) but was associated with subcellular organelles. Although there was a slight tendency for CAD to be localized in the vicinity of the nuclear envelope, the amount of staining was much less than expected from differential centrifugation, which showed that 30% of the protein was found in the nuclear fraction. No interactions with other subcellular components could be detected by centrifugation. It is possible, however, that CAD is associated with subcellular structures that cosediment with the nuclei. Despite a 150-fold increase in CAD concentration in the over producing cells, the distribution of the protein was unaltered. CAD was not concentrated near the mitochondria where the next enzyme of the de novo pathway, dihydroorotate dehydrogenase, is localized, which indicates that the intermediate dihydroorotate is not channeled, but rather dissociates from CAD and diffuses through the bulk cellular fluid. PMID- 2903108 TI - Gel-filtration of serum gamma-glutamyl-transpeptidase with HPLC in hepatobiliary diseases and its significance. AB - Serum gamma-glutamyl-transpeptidase (gamma-GTP) from patients with various hepatobiliary diseases was fractionated by molecular size using HPLC to investigate the heterogeneity of serum gamma-GTP. Serum gamma-GTP eluted with HPLC showed essentially 3 elution peaks of different molecular size. In the sera of normal patients, there was little gamma-GTP in the high molecular fraction, and most occurred in the low molecular fraction. Intermediate molecular gamma-GTP appeared only in the sera of patients with hepatobiliary disease. In the sera of patients with extrahepatic biliary obstruction, the percentage of high molecular gamma-GTP to total serum gamma-GTP activity was higher than that of other patients. High molecular gamma-GTP increased in the sera of patients with extrahepatic biliary obstruction. Intermediate molecular gamma-GTP appeared in the relatively higher molecular fraction in the sera of patients in whom alcohol consumption might have caused serum gamma-GTP increase, and in the relatively lower molecular fraction in the sera of patients with extrahepatic biliary obstruction. It was concluded, therefore, that the position of elution of intermediate molecular gamma-GTP corresponded to the morbid state. It was shown that intermediate molecular gamma-GTP appeared in the relatively low molecular fraction, corresponding to the increase of serum total bile acids concentration. PMID- 2903109 TI - Changes of plasma insulin glucagon and somatostatin in portal blood and morphological changes of islets of Langerhans after hepatectomy in dogs. AB - Hybrid adult male dogs were laparotomized before, one week after and one month after 40% hepatectomy. At the same time, an intravenous glucose tolerance test was done (IV-GTT) and pancreatic tissues were removed and examined by PAP staining. The following results were obtained: Carbohydrate metabolism was disturbed and plasma insulin levels were low one week after surgery, but B-cell granulations was at the preoperative level. It seemed that hypersomatostatinemia suppressed insulin release from B cells. Carbohydrate metabolism was restored to normal and the plasma insulin response was increased one month after surgery. Islets of Langerhans cells were hypertrophic and increased after surgery, particularly D cells. PMID- 2903110 TI - Double-blind comparison of slow-release 5-aminosalicylate and sulfasalazine in remission maintenance in ulcerative colitis. AB - The results of a clinical trial comparing slow-release 5-aminosalicylic acid tablets (Pentasa) and enteric-coated sulfasalazine tablets (Salazopyrin) with regard to the efficacy of maintaining ulcerative colitis patients in remission for 12 mo and with regard to safety of treatment are reported. Seventy-five patients with ulcerative colitis in remission for between 1 mo and 5 yr were included for analysis. Forty-nine men and 26 women, aged between 18 and 79 yr, received either Pentasa t.i.d. (1500 mg) plus Salazopyrin placebo or Salazopyrin t.i.d. (3 g) plus Pentasa placebo daily. Patients were assessed clinically, endoscopically, and histologically before and 3, 6, 9, and 12 mo after the start of treatment. Life-table analysis showed ongoing remission after 6 and 12 mo for Pentasa to be 63% (26 of 41) and 54% (22 of 41) and for Salazopyrin 72% (22 of 31) and 46% (14 of 31). These differences were not statistically significant. Three patients treated with Salazopyrin were withdrawn because of severe erythrodermia, anxiety and backache, and pregnancy, respectively. One patient on Salazopyrin experienced transient rises in serum urea, creatinine, and lactic dehydrogenase and another patient in this group reported slight reversible loss of hair. In the Pentasa group no side effects were recorded. We conclude that Pentasa is a well-tolerated drug, equally effective as Salazopyrin in maintenance of remission of ulcerative colitis. PMID- 2903112 TI - Remission of Crohn's disease after human immunodeficiency virus infection. AB - A patient with an 18-yr history of Crohn's disease of the colon became infected with the human immunodeficiency virus. The patient had a complete remission of gastrointestinal symptoms in association with progressive immunodeficiency. This finding suggests that CD4 T cells and an intact immune response play a central role in the pathogenesis of Crohn's disease. PMID- 2903111 TI - Effects of gastrin, proglumide, and somatostatin on growth of human colon cancer. AB - The effects of gastrin, proglumide (a gastrin receptor antagonist), and somatostatin on growth of human colon adenocarcinoma cell lines CX1, X56, and HT29 were examined in two experimental models. Nude mice bearing xenografts of colon cancer CX1 or X56 were treated for 14-25 days subcutaneously with saline, pentagastrin (0.5 or 1.0 mg/kg), proglumide (250 or 500 mg/kg), or somatostatin 14 (33, 100, or 300 micrograms/kg) twice daily. Tumor volume, weight, protein, and deoxyribonucleic acid were measured. HT29 cells were grown in vitro and the effects of gastrin 17, proglumide, and somatostatin on growth were evaluated by cell counts or [3H]thymidine incorporation. The larger dose of pentagastrin significantly increased tumor growth in the nude mouse (p less than 0.005) and gastrin induced a biphasic effect on deoxyribonucleic acid synthesis in tissue culture with significant increases of up to 39% (p less than 0.025). Somatostatin alone significantly inhibited tumor growth in two of the cell lines and also inhibited the gastrin-induced growth. Proglumide had no effect by itself but significantly inhibited gastrin-stimulated growth. These findings suggest that growth of some human colon cancers may be hormone-dependent. PMID- 2903113 TI - Update on the aminosalicylates: a promise fulfilled. PMID- 2903114 TI - Tunable dye laser lithotripsy: in vitro studies and in vivo treatment of choledocholithiasis. PMID- 2903115 TI - [Neurohumoral regulation of the adaptive processes in workers subjected to toluene diisocyanate exposure]. PMID- 2903116 TI - Cerebral infarction due to systemic necrotizing vasculitis in a patient with rheumatic heart disease, subacute bacterial endocarditis and status epilepticus. AB - Systemic necrotizing vasculitis involving cerebral blood vessels is described in a 30-year-old man with rheumatic heart disease and subacute bacterial endocarditis. Fever, anaemia, splenomegaly and positive blood cultures for Gram negative bacteria were found on admission. The fever resolved with antibiotic therapy on the third hospital day but he then developed hemiplegia and multifocal seizures. The seizures progressed to uncontrollable status epilepticus accompanied by congestive heart failure and the patient died 20 d after admission. At autopsy, exudative and necrotizing vasculitis involving medium- to small-sized arteries was seen in the brain, the heart and the skeletal muscles. Rheumatic myocarditis and endocarditis and old rheumatic mitral valve deformities were also present. In addition, verrucous endocarditis in the mitral valve and Lohlein's focal glomerulonephritis were noted. We discuss the possible mechanism of the systemic necrotizing vasculitis in relation to rheumatic fever. PMID- 2903117 TI - Immunopathogenesis of occlusive thromboaortopathy (OTAP). PMID- 2903119 TI - Enzyme-linked immunosorbent assay in the detection of antigen in amoebic liver abscess. PMID- 2903118 TI - Attempt to detect recombination between B-F and B-L genes within the chicken B complex by serological typing, in vitro MLR, and RFLP analyses. AB - In search for recombinants within the chicken major histocompatibility B complex, 1155 animals from crosses between the congenic lines CB (B12) and CC (B4) were tested with alloantibodies and monoclonal antibodies for the B-F (class I), B-L (class II), and B-G (class IV) antigens and by mixed lymphocyte reaction. The absence of detectable recombination was confirmed by restriction fragment length polymorphism analysis with B-L beta and B-F probes. Together with previous reports, this indicates that the distance between the B-F and B-L loci is below 0.01 centimorgan. PMID- 2903120 TI - Toxic effect of seaweed extracts on mosquito larvae. PMID- 2903121 TI - Haemagglutination & electron microscopy of enterotoxigenic & nontoxigenic Escherichia coli. PMID- 2903122 TI - Inhibition of activated nonresponder C3H/HeJ lymphocytes by lipopolysaccharide endotoxin. AB - The B lymphocytes and macrophages of lipopolysaccharide (LPS) nonresponder C3H/HeJ mice were found to respond to certain R types of LPS endotoxin in a fashion resembling that ordinarily seen with the cells from normal responder mice. DNA synthesis, polyclonal antibody synthesis, and interleukin-1 activity were stimulated by Bordetella pertussis LPS and Salmonella minnesota R595 LPS, although to a lesser extent than with responder cells. Mitogenesis stimulated by both LPSs was inhibited by polymyxin B; this finding provided evidence that any trace endotoxin-associated proteins were not responsible for the activity. Of particular interest was the finding that wild-type smooth LPS actually inhibited activation of the C3H/HeJ B cells not only by the LPS but also by mitogenic proteins, including purified protein derivative of tuberculin. The nonspecific nature of this inhibition and the fact that maximal inhibition occurred some 9 to 12 h into the culture period suggested that the proliferation of the B cells was affected by smooth-type LPS in a manner heretofore unrecognized. These findings permit a new approach to the study of how LPS endotoxin affects cells of the immune system. PMID- 2903123 TI - Roles of CD4- and CD8-bearing T lymphocytes in the immune response to the erythrocytic stages of Plasmodium chabaudi. AB - The possible role of CD4- and CD8-bearing T lymphocytes in parasite clearance in vivo was investigated, using Plasmodium chabaudi in C57BL/6 mice as a model. Monoclonal antibodies specific for the CD4 and CD8 molecules were administered in vivo to deplete selectively the appropriate subset of T cells. The efficacy of depletion was ascertained by flow cytometry and functional studies. These mice were then infected with P. chabaudi, and the course of infection was followed. The control groups had maximum parasitemias of approximately 30% 10 days after infection, and the infection was cleared within 27 days. Mice without CD4+ cells had significantly higher parasitemias which they were unable to reduce below 20% for the duration of the experiment. Mice without CD8 cells had slightly higher parasitemias which were cleared after 34 days. Because of the possibility that CD8+ cells alone could not be activated in the absence of growth factors, exogenous interleukin-2 was administered to the mice depleted of CD4 cells. This did not significantly affect parasitemias, and the mice were still unable to clear their infections. The data suggest that CD4+ T cells play a crucial role in the protective immune response to the erythrocytic stages of P. chabaudi. PMID- 2903124 TI - In vitro and in vivo studies of macrophage functions in amebiasis. AB - Experimental intrahepatic inoculation of the gerbil with Entamoeba histolytica trophozoites was used as a model of liver amebiasis to study the cellular immune response elicited by the parasite. It was shown that abscess-derived macrophages (5 to 20 days old) were deficient in their capacity to develop a respiratory burst, to secrete and express membrane-bound interleukin-1-like activity, and to kill E. histolytica trophozoites as well as to respond to lymphokines in vitro. However, macrophages isolated from the spleen and peritoneal cavities from the same infected animals were not significantly down regulated in these functions. Splenocytes from infected gerbils were shown to develop a strong responsiveness to amebic antigen, whereas their response to concanavalin A was suppressed. Crude E. histolytica extracts or conditioned medium down regulated murine BALB/c macrophage accessory and effector cell functions in vitro in a manner similar to abscess-derived macrophages, whereas crude extracts of the nonvirulent E. histolytica-like Laredo strain did not. Our results indicate that intrinsic or secreted products or both from E. histolytica are actively regulating macrophage functions at the abscess site and can possibly mediate other immunoregulatory mechanisms at distant targets. PMID- 2903125 TI - Comparison of type 2 and type 6 fimbriae of Bordetella pertussis by using agglutinating monoclonal antibodies. AB - Two types of fimbriae have been identified on the pathogenic gram-negative organism Bordetella pertussis. Monoclonal antibodies to these fimbriae were produced to better understand the role of fimbriae as serotype-specific agglutinogens and to investigate the antigenic relationship between these fimbriae. Three monoclonal antibodies were identified that specifically agglutinated B. pertussis cells containing the U.S. Reference Factor 2 agglutinogen, and six monoclonal antibodies were produced that agglutinated only those strains containing the U.S. Reference Factor 6 agglutinogen. Indirect immunofluorescence studies and immunogold electron microscopy demonstrated that these monoclonal antibodies bind to an outer membrane component on serotype specific strains of B. pertussis. All of the monoclonal antibodies reacted with native or partially assembled type-specific fimbriae but not with monomeric fimbrial subunits as indicated by Western blot (immunoblot) analysis. The fimbrial agglutinogens recognized by the monoclonal antibodies were also uniquely reactive with either U.S. Reference Factor 2 or 6 antiserum (Eldering agglutinogen 2 or 6 polyclonal antiserum) in an indirect ELISA. No cross reactivity of the monoclonal antibodies with the unrelated fimbriae was observed in any of the comparative immunological studies. Some of the monoclonal antibodies agglutinated certain strains of B. bronchiseptica, suggesting that this closely related species can contain antigenically similar fimbriae. These monoclonal antibodies should prove useful for further structural and functional analysis of Bordetella fimbriae and for studies on the role that these antigens play in prevention of infection and disease. PMID- 2903126 TI - Identification of a 69-kilodalton nonfimbrial protein as an agglutinogen of Bordetella pertussis. AB - Cells of Bordetella pertussis BP353, a nonfimbriated Eldering serotype 1.3 strain, were used as an immunogen to produce three monoclonal antibodies, BPE3, BPD8, and BPE8, that agglutinated the immunizing cells, as well as certain other nonfimbriated and fimbriated serotype 3-containing B. pertussis strains. The antibodies did not agglutinate serotype 1 or nontypable B. pertussis cells. These monoclonal antibodies specifically detected a 69-kilodalton (kDa) band on Western blots (immunoblots) containing whole B. pertussis cell lysates of Eldering agglutinogen serotypes 1.3, 1.3.6, 1.2.3.4, and 1.2.3.4.6. This 69-kDa antigen was released from the bacteria by cell incubation for 60 min at 60 degrees C, and it was purified by affinity chromatography with a BPE3-agarose affinity matrix. Purified material was used to produce a polyclonal antiserum that agglutinated all nonfimbriated and fimbriated B. pertussis cells containing serotype 3 agglutinogen. Immunogold electron microscopy and indirect immunofluorescence studies demonstrated that it is an outer membrane constituent but nonfimbrial in appearance. BPE3 did not detect purified fimbriae on Western blots, and antibodies to these fimbriae did not bind to the 69-kDa component. Although B. bronchiseptica and B. parapertussis cells were not agglutinated by the monoclonal antibodies, antigenically similar proteins were detected in extracts of the bacteria. These results identify the 69-kDa protein as a nonfimbrial agglutinogen present on all virulent strains of B. pertussis. The monoclonal antibodies described here should be useful for further studies on the structure and function of this protein. PMID- 2903127 TI - Cloning and expression in Escherichia coli of the perfringolysin O (theta-toxin) gene from Clostridium perfringens and characterization of the gene product. AB - The gene encoding perfringolysin O, the thiol-activated hemolysin from Clostridium perfringens (ATCC 13124), was cloned and expressed in Escherichia coli. A gene library of C. perfringens chromosomal DNA was constructed in bacteriophage lambda EMBL3. A recombinant was identified that produced a hemolysin that was inhibited by cholesterol and was tentatively identified as perfringolysin O. Subcloning experiments localized the perfringolysin O gene (pfo) to a 1.8-kilobase region on the cloned chromosomal fragment. E. coli which carried a plasmid subclone of pfo (pRT1B) expressed perfringolysin O and secreted it into the periplasm. The amino-terminal sequence of the pfo gene product was identical with that determined for perfringolysin O purified from C. perfringens, indicating that E. coli correctly removed the signal peptide during secretion. Purification of the pfo product was accomplished by high-resolution gel filtration and anion-exchange chromatography. Analysis of the pfo product by sodium dodecyl sulfate gel electrophoresis showed that it comigrated with authentic perfringolysin O; both had an estimated molecular weight of 54,000. Two dimensional tryptic peptide maps of the pfo product and of authentic perfringolysin O purified from C. perfringens were identical. The hemolytic activity of the pfo product was similar to that of authentic perfringolysin O; one hemolytic unit (HU) of the cloned gene product or authentic perfringolysin O corresponded to approximately 1 ng or a hemolytic activity of 10(6) HU per mg. PMID- 2903128 TI - Nucleotide sequence of the gene for perfringolysin O (theta-toxin) from Clostridium perfringens: significant homology with the genes for streptolysin O and pneumolysin. AB - The nucleotide sequence was determined for the gene encoding the thiol-activated cytolysin, perfringolysin O (theta-toxin), from Clostridium perfringens. The nucleotide-sequence-derived primary structure of perfringolysin O is 499 residues long and exhibits a 27-amino-acid signal peptide. The calculated molecular weight of the secreted (mature) form of perfringolysin O is 52,469. The deduced amino terminal sequence of perfringolysin O is identical to that determined for purified perfringolysin O. Hydropathy analysis indicated that, except for the signal peptide, no major stretches of hydrophobic residues are present. Extensive amino acid sequence homology (65%) was detected with the low-molecular-weight form of streptolysin O, and a lesser amount (42%) was detected with pneumolysin. The nucleotide sequence of the perfringolysin O gene (pfo) exhibits approximately 60% homology with the streptolysin O gene (slo) and 48% homology with the pneumolysin gene (ply). All three toxins contain an identical region of 12 amino acids, which includes the essential cysteine of all three toxins. The location of these 12 residues was conserved in all three toxins when the primary sequences were aligned for maximum homology. PMID- 2903129 TI - Vibrio cholerae O1 adherence to villi and lymphoid follicle epithelium: in vitro model using formalin-treated human small intestine and correlation between adherence and cell-associated hemagglutinin levels. AB - Formalin-fixed human small intestinal mucosa possessing villi and lymphoid follicle epithelium of Peyer's patches at the mucosal surface was used to test the adherence ability of clinically isolated strains of Vibrio cholerae O1. V. cholerae O1 grown on CFA agar for approximately 3 h at 37 degrees C had various levels of cellular hemagglutinins (HAs) and manifested adherence abilities that were roughly correlated with the cellular HA levels, irrespective of cellular HA types. V. cholerae O1 adhered better to epithelium over ileal lymphoid follicles than to epithelium of jejunal or ileal villi. Cells of different morphology which constituted lymphoid follicle epithelium were almost equal targets for adherence. In contrast, V. cholerae O1 grown on CFA agar for approximately 20 h at 37 degrees C in many cases had lower levels of cellular HAs and adherence abilities. Contrary to the above observations with cellular HAs and adherence, piliation of V. cholerae O1 was rather more extensive at approximately 20 h of incubation at 37 degrees C than at approximately 3 h of incubation at 37 degrees C. L-Fucose inhibited adherence to a varied extent depending on the cellular HA types, while D-mannose enhanced adherence in some strains. Heating of V. cholerae O1 diminished adherence ability. This adherence model system provides a tool by which various V. cholerae O1 strains can be preliminarily tested for adherence ability and site in human small intestine. PMID- 2903131 TI - Opposite effects of amines on lymphocyte- and monocyte-mediated ADCC. AB - The effect of different amines on antibody-dependent cellular cytotoxicity (ADCC) activity of human mononuclear cells was tested. Whereas monocyte cytotoxic capacity was significantly stimulated in the presence of methylamine (MA), dansylcadaverine (DC) and glycine ethylester (GEE), lymphocyte ADCC was markedly suppressed by these agents. The pharmacological actions of these compounds in our system are not related to their ability to inhibit transglutaminase (TGase) enzymes, since tertiary amines such as sarcosine ethylester (SEE) and chloroquine (CQ) elicited identical responses to MA, DC and GEE. The calmodulin (CAM) inhibitors trifluoperazine (TFP) and the more specific N-(6-aminohexyl)-5-chloro 1-naphtalene sulfonamide (W-7) [Hidaka, Sasaki, Tanaka, Endo, Ohno, Fujii & Nagata (1981) Proc. natn. Acad. Sci. U.S.A., 78, 4353-4357] mimicked the effects of amines on ADCC, suggesting the possibility that a CAM-regulated process might be involved in the functional changes provoked by amines on ADCC. Finally, binding of 125I-immune complexes to the effector cells in the presence of amines showed lack of correlation between alterations in ADCC capacity and Fc gamma R expression. PMID- 2903130 TI - Nucleotide sequence of the gene encoding the major subunit of CS3 fimbriae of enterotoxigenic Escherichia coli. AB - The complete nucleotide sequence of a 612-base-pair DNA fragment containing the gene for the major fimbrial subunit of CS3 of enterotoxigenic Escherichia coli is presented. A possible promoter region, a ribosome-binding site, and two potential signal peptidase cleavage sites are indicated. Unlike the best-studied fimbrial proteins, the predicted CS3 sequence has no Cys residues. PMID- 2903132 TI - T lymphocytes and cervical intraepithelial neoplasia. PMID- 2903133 TI - Depression of hypoxic ventilatory response in humans by somatostatin. AB - In nine normal subjects we measured the ventilatory response to isocapnic hypoxia with and without an intravenous infusion of 1 mg of somatostatin. Arterial O2 saturation was rapidly lowered to 80 +/- 2% in 2 min and maintained for 30 min. During control experiments, ventilation increased immediately (3-5 min) and then declined so that at 25 min of hypoxia ventilation was little above that in room air. Somatostatin was associated with a small decrease in ventilation while the subjects breathed room air. With hypoxia there was no immediate increase in ventilation for the group as a whole, although an increase was observed in one subject. With somatostatin, after 25 min of hypoxia, mean ventilation was lower than at any other time in the study; as hypoxia was discontinued ventilation increased slightly. Somatostatin causes profound depression of the ventilatory response to hypoxia by a mechanism that is not known but may be central. With somatostatin hypoxia of 25-min duration tends to depress ventilation. PMID- 2903134 TI - Central respiratory effects of glutamine synthesis inhibition in dogs. AB - Glutamic acid is an excitatory neurotransmitter that may have a significant role in the central chemical drive of ventilation. Therefore cardiorespiratory function was measured in pentobarbital sodium-anesthetized dogs before and after central inhibition of glutamate metabolism by means of methionine sulfoximine (MSO), a specific inhibitor of glutamine synthase (GS) catalyzing amidation of glutamate to glutamine. GS was inhibited centrally by perfusing the ventriculocisternal space with artificial cerebrospinal fluid (CSF) containing 92.5 mmol MSO per liter at a fixed pH, perfusion rate, and pressure. After GS inhibition, CSF transfer rate of [13N]glutamine synthesized from 13NH4+ amidation of glutamate was reduced five-fold, and minute ventilation increased from 2.90 +/ 0.41 (SE) l/min (0.164 +/- 0.020 l.min-1.kg body wt-1) to 4.46 +/- 0.52 l/min (0.254 +/- 0.029 l.min-1.kg body wt-1). This increase in ventilation with endogenous glutamate and the increase in ventilation previously observed during ventriculocisternal perfusion of exogenous glutamate are compared quantitatively via a model of central neurotransmitter glutamate chemoreception. The results support the hypothesis that the endogenous brain glutamate is important in the central chemical drive of ventilation. PMID- 2903135 TI - Absence of neural modulation of hypoxic pulmonary vasoconstriction in conscious dogs. AB - Our objectives were 1) to quantify the magnitude of the hypoxic pulmonary vasoconstrictor (HPV) response in conscious dogs by utilizing pulmonary vascular pressure-cardiac index (P/Q) plots and 2) to assess the extent to which the autonomic nervous system (ANS) modulates the HPV response. Multipoint P/Q plots were constructed in conscious dogs during normoxia and during bilateral alveolar hypoxia by stepwise constriction of the thoracic inferior vena cava to reduce Q. With the ANS intact, the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) increased (P less than 0.01) approximately twofold during hypoxia over a broad range of Q. The absolute magnitude of the HPV response was related (P less than 0.01) to the level of Q. We hypothesized that if ANS activation reduces the magnitude of HPV in intact dogs, then we would expect the magnitude of HPV to be increased both after combined sympathetic alpha-(phentolamine) and beta-(propranolol) adrenergic block and after total autonomic ganglionic block (hexamethonium). A marked HPV response (P less than 0.01) was observed after both combined sympathetic block and ganglionic block over a broad range of Q during alveolar hypoxia. The magnitude of the HPV response with the ANS intact, however, was not significantly different from the magnitude of HPV after combined sympathetic block (P = 0.45) or after ganglionic block (P = 0.64) at any level of Q. Thus, during bilateral alveolar hypoxia, the ANS does not appear to attenuate the HPV response of intact conscious dogs. PMID- 2903136 TI - Development and characterization of a human cell line from an ovarian mixed Mullerian tumor (carcinosarcoma). AB - A cell line derived from a human ovarian carcinosarcoma was established in tissue culture and in nude mice. Two sublines, LDF and HDF, separated by discontinuous density centrifugation were also established from the parent line JoN. The cloning efficiency of the JoN line was 21%. Morphologic features of adenocarcinoma cells characteristic of the parent JoN cells were retained in the sublines and clones; all lines showed the same karyotype and DNA content (pseudodiploid and pseudotetraploid). Keratin, as demonstrated immunohistochemically, was strongly expressed in the parent line JoN and the xenograft tumor, but not at all in the LDF sublines and only moderately in the HDF sublines. Vimentin, however, was expressed in neither the parent line JoN nor the xenograft tumor, but was present in both sublines. Transglutaminase and plasminogen activator activity was high in the parent line JoN. Neither, sublines nor clones showed the same high enzyme activity as the parent line. It is concluded that this human tumor line JoN is comprised of epithelial cells, capable of multidirectional differentiation. PMID- 2903137 TI - A method for the comparative study of replicative DNA synthesis in GGT-positive and GGT-negative hepatocytes in primary culture isolated from carcinogen-treated rats. AB - The presence of gamma-glutamyl transpeptidase (GGT) in focal nodules of hepatocytes is a commonly used marker for the identification of preneoplastic cell populations. Female Fischer 344 rats were initiated with a single intragastric administration of 200 mg diethylnitrosamine/kg, altered cells were selected after 0.02% 2-acetylaminofluorene was given in the diet; this was followed by a partial hepatectomy and promotion with dietary sodium phenobarbital for 4 wk. A mixed-cell population of GGT-positive and GGT-negative hepatocytes was obtained after collagenase perfusion and Percoll purification. An enriched population of GGT-positive hepatocytes was obtained by a modified "panning" technique. With quantitative scintillation spectrometry and autoradiography of [3H]thymidine incorporation, replicative DNA synthesis of GGT-positive and GGT negative rat hepatocytes was observed in both the mixed-cell population and the enriched GGT-positive and GGT-negative cell populations. Under the culture conditions used, GGT-positive cells showed a higher level of replicative DNA synthesis than did GGT-negative cells; this indicates that such altered hepatocytes in the stage of promotion possess an inherently greater capacity for all replication, as previously suggested from studies in vivo. PMID- 2903138 TI - Common cardiac drugs and rehabilitation. AB - Cardiac patients are often on drugs. They invariably benefit from a rehabilitation programme where they may be seen more frequently than in a routine follow-up clinic. Rehabilitation units must keep alert for drug-induced adverse effects or symptomatic deterioration, as well as the more usual psychological and physical benefits they induce. PMID- 2903139 TI - Sulphasalazine in the treatment of rheumatoid arthritis in India. PMID- 2903140 TI - Two trans-acting regulatory genes (vir and mod) control antigenic modulation in Bordetella pertussis. AB - Expression of virulence factors by Bordetella pertussis is altered by environmental signals (antigenic modulation) and is dependent on an activator encoded by a gene called vir. We have used TnphoA (Tn5 IS50L::phoA) gene fusions to define two sets of genes whose expression is either activated (vag loci) or repressed (vrg loci) by modulation signals. Both groups of genes appear to be regulated by the vir gene product in that, in the absence of modulators, null mutations in vir lead to the repression of vag gene fusions and derepression of vrg gene fusions. Mutants of B. pertussis were isolated that constitutively express virulence factors in the presence of the modulator MgSO4, nicotinic acid, or low incubation temperature. We designate the gene that carries such mutations mod (modulation) and have characterized one (mod-1) of these mod constitutive mutations. A method was developed for the insertional inactivation of the vir gene by using the integration of a suicide replicon. Inactivation of the vir gene in the mod-1 mutant, followed by transcomplementation with the cloned wild-type vir gene, gives the Mod-1 constitutive phenotype, showing that the mod-1 mutation defines a gene distinct from vir. The gene carrying the mod-1 mutation is linked to vir and was cloned on a recombinant cosmid (pLAF-C1) which transcomplements the vir-1::Tn5 mutation in B. pertussis 347. Introduction of pLAF-C1 into vir mutant and vir+ B. pertussis strains also gives the Mod-1 constitutive phenotype, indicating that mod-1 is a dominant allele. These data suggest that the mod gene product could have sensory functions for the environmental signals that affect the expression of vir-regulated genes of B. pertussis. The mod constitutive strains and plasmids described here also have applications in pertussis vaccine development. PMID- 2903141 TI - Antipsychotic-withdrawal akathisia versus antipsychotic-induced akathisia: further evidence for the existence of tardive akathisia. AB - The authors present a study in which 33 chronic schizophrenic patients who, when withdrawn from antipsychotic drug treatment for more than 2 weeks, presented with concurrent signs of akathisia and tardive dyskinesia; however, signs of akinesia, facial masking, rigidity, or dystonia were not concurrent with the patients' akathetic presentation. In a subsequent study phase, these patients were treated with antipsychotics for up to 6 weeks. The dyskinetic signs that had been dramatically more severe in those patients exhibiting akathisia following withdrawal from antipsychotic medication continued for up to 6 weeks following the renewal of antipsychotic drug therapy. These findings help to confirm a relationship between tardive dyskinesia and a persistent akathisia of later onset known as tardive akathisia. PMID- 2903142 TI - The role of neuroleptics in manic-depressive illness. AB - Neuroleptic drugs are a common treatment for acute mania. Although lithium alone may be effective, for those patients with moderate or severe agitation neuroleptics appear to be superior. Low-potency and high-potency neuroleptics are equally effective in mania, as in schizophrenia. Patients with affective disorders, however, may be highly susceptible to the pseudoparkinsonian or extrapyramidal side effects that can occur with neuroleptics. Moderate doses of neuroleptics can be effective in most patients and can reduce the likelihood of serious side effects. Many bipolar patients have manic relapses despite adequate serum lithium levels, and many of those patients are subsequently maintained on a regimen of neuroleptic drugs in addition to lithium. Using the lowest possible dose of the neuroleptic may decrease the high, long-term risk of tardive dyskinesia. More clinical research is needed to determine the most appropriate use of neuroleptic drugs in bipolar disorder. PMID- 2903143 TI - The use of benzodiazepines in the treatment of manic-depressive illness. AB - The benzodiazepine clonazepam was approved for the treatment of epilepsy in 1976. To study its use in acute mania, the author compared clonazepam with lithium in a crossover trial. Clonazepam proved more effective than lithium in controlling the symptoms of mania and caused fewer manifestations of parkinsonism. Associated side effects included ataxia, drowsiness, and behavioral changes. No treatment emergent depression was observed. Neither clonazepam nor any other benzodiazepine is recommended in schizoaffective or schizophrenic disorders because of the high risk of dependence in those patients, in contrast to manic-depressives. For the maintenance treatment of bipolar disorder, lithium is recommended as the initial agent, with L-tryptophan added if concomitant medication is needed. Clonazepam can then be added as the anticonvulsant, if necessary. In the treatment of acute mania, clonazepam is recommended for the first week of treatment, and lithium is added in the beginning of the second week, thus avoiding the use of neuroleptics. PMID- 2903144 TI - Inhibitory effect of taurolipids on Clostridium perfringens sialidase. AB - Taurolipids A and B, which are detergent-type compounds isolated from protozoan Tetrahymena cells, were demonstrated to inhibit strongly the activity of Clostridium perfringens sialidase. On addition of 280 pmol of taurolipid B to 20 mU of the enzyme, the sialidase activity was decreased to 7% of the original activity at pH 5.1 as the optimum pH. The inhibition was non-competitive. Effective inhibition was observed at the acidic region from the isoelectric point of the sialidase, and at a low ionic strength. Both the long chain acyl and sulfonic acid groups of taurolipids were required for the inhibition of the sialidase activity. A mechanism is postulated for the inhibition. PMID- 2903145 TI - Resonance Raman spectra of anionic semiquinoid form of a flavoenzyme, D-amino acid oxidase. AB - Resonance Raman (RR) spectra of the complex of anionic semiquinoid D-amino acid oxidase (DAO) with picolinate in H2O and D2O were observed in the 300-1,750 cm-1 region. RR spectra were also measured for the complex of the semiquinoid enzyme reconstituted with isotopically labeled FAD's, i.e., [4a-13C]-, [4,10a-13C2]-, [2 13C]-, [5-15N]-, and [1,3-15N2]-FAD. On the basis of the isotope effects, tentative assignments of the observed bands of the anionic semiquinoid flavin were made. The spectra differ from those of oxidized, neutral semiquinoid, and anionic reduced flavins previously reported. The 1,602 cm-1 band was not shifted for any FAD labeled in ring II and/or ring III and was assigned to a ring I mode. The 1,516 cm-1 band underwent an isotopic shift upon [4a-13C]- or [4,10a-13C2] labeling. The band was assigned to the mode containing C(4a)-C(10a) stretching. The 1,331 and 1,292 cm-1 bands shifted upon [4a-13C]- or [5-15N]-labeling and were assigned to the modes containing C(4a)-N(5) stretching. The 1,217 and 1,188 cm-1 bands were assigned to the skeletal vibrations of ring III coupled with the N(3)-H bending mode. The RR spectrum of the complex of anionic semiquinoid DAO with alpha-iminopropionate or N-methyl-alpha-iminopropionate was essentially identical with that of the complex with picolinate. PMID- 2903147 TI - The plasma membrane H+-ATPase of Neurospora crassa. Properties of two reactive sulfhydryl groups. AB - Previous work with N-ethylmaleimide (NEM) has defined two sites on the Neurospora plasma membrane H+-ATPase. Modification of one (the "fast" site) by NEM is rapid but does not affect ATPase activity, while modification of the other (the "slow" site) inactivates the enzyme and is protectable by MgATP or MgADP. In the present study, a wider array of sulfhydryl reagents have been used to examine the properties of both sites. The results show the following. (a) Both fast and slow sites react preferentially with hydrophobic compounds (N-pyrenemaleimide, dithiobisnitropyridine greater than N-naphthylmaleimide, dithiobisnitrobenzoate greater than N-phenylmaleimide greater than N-ethylmaleimide) and are virtually insensitive to hydrophilic sulfhydryl reagents such as iodoacetamide and iodoacetic acid. (b) The reaction rate of the slow site with NEM is approximately 2000-fold less rapid than that of the fast site. The slow site also has an unusually high pKa (greater than 9.5). (c) Whether or not cysteine modification leads to inactivation of the ATPase depends upon the site and the reagent. For example, when the fast site reacts with NEM, enzymatic activity is retained; when it reacts with N-pyrenemaleimide, activity is lost. Likewise, when the slow site is modified by any of the maleimides or by dithiobisnitropyridine or dithiobisnitrobenzoate, the ATPase is inactivated; when it is modified by methylmethanethiosulfonate, activity remains intact. Thus, neither cysteine can be considered to play an essential role in the reaction cycle of the ATPase, but the introduction of a sufficiently bulky substituent at either site can disrupt activity. (d) Upon reaction of methylmethanethiosulfonate at the slow site, the K1/2 for MgATP hydrolysis is reduced from 0.65 to 0.25 mM. This result strengthens the evidence for a conformational relationship between the slow site cysteine and the nucleotide binding site of the ATPase. PMID- 2903146 TI - Directed mutagenesis of the strongly conserved lysine 175 in the proposed nucleotide-binding domain of alpha-subunit from Escherichia coli F1-ATPase. AB - The alpha-subunit of Escherichia coli F1-ATPase contains an adenine-specific noncatalytic nucleotide-binding domain. A recent proposal (Maggio, M. B., Pagan, J., Parsonage, D., Hatch, L., and Senior, A. E. (1987) J. Biol. Chem. 262, 8981 8984) suggested that this domain is formed by residues 160-340, approximately, in alpha-subunit. Within this proposed domain is a sequence Gly-X-X-X-X-Gly-Lys which is conserved in a large and diverse group of nucleotide-binding proteins and is thought to interact with phosphate groups of bound nucleotide. In this work, residue alpha Lys-175, the terminal residue of the above conserved sequence in F1-alpha-subunit, was mutagenized to Ile or Glu. The specific activity of purified mutant F1-ATPase was reduced by 2.5-fold (Ile) or 3-fold (Glu). Apparent binding of ATP to alpha-subunit, as measured by the centrifuge column procedure, was strongly impaired and ATP-induced conformational change in alpha-subunit, as measured by protection against trypsin proteolysis, was nearly abolished in both mutants. The results suggest that residue alpha Lys-175 is located within the nucleotide-binding domain of alpha-subunit, and that this residue is functionally involved in nucleotide binding. The results support previous suggestions that the alpha-subunit nucleotide-binding site is not involved, directly or indirectly, in catalysis. PMID- 2903148 TI - The structure and biosynthesis of new tetrahydropyrimidine derivatives in actinomycin D producer Streptomyces parvulus. Use of 13C- and 15N-labeled L glutamate and 13C and 15N NMR spectroscopy. AB - Two novel compounds, 2-methyl, 4-carboxy, 5-hydroxy-3,4,5,6-tetrahydropyrimidine (THP(A] and 2-methyl, 4-carboxy-3,4,5,6-tetrahydropyrimidine (THP(B] have been identified in the pool of Streptomyces parvulus by in vivo and in vitro studies. 13C and 15N were introduced into the compounds by feeding S. parvulus with 15N- and 13C-labeled L-glutamate. High resolution 13C and 15N NMR have been applied to elucidate their structure and biosynthesis in S. parvulus. The splitting patterns and coupling constants of adjacent nitrogen-carbon molecular fragments enable us to unravel their molecular structure. Two different glutamate pools are responsible for their biosynthesis, THP(A) carbon skeleton derives from the extracellular L-[13C]glutamate, whereas THP(B) stems from D-fructose via the intracellular glutamate. During cell growth, THP(A) is synthesized and becomes the major constituent of the intracellular pool. It is consumed after THP(B) is accumulated intracellularly. The onset of THP(A) and -(B) synthesis seems correlated to the time of actinomycin D synthesis. Their high cellular concentrations during actinomycin D synthesis suggest that they may function as nitrogen storage. Other possible functions of THP molecules within the cell are discussed. PMID- 2903149 TI - The pH dependence of binding of inhibitors to bovine adrenal tyrosine hydroxylase. AB - The inhibition of purified bovine adrenal tyrosine hydroxylase by several product and substrate analogues has been studied to probe the kinetic mechanism. Norepinephrine, dopamine, and methylcatechol are competitive inhibitors versus tetrahydropterins and noncompetitive inhibitors versus tyrosine. 3-Iodotyrosine is an uncompetitive inhibitor versus tetrahydropterins and a competitive inhibitor versus tyrosine. The Ki value for 3-iodotyrosine depends on the tetrahydropterin used. These results are consistent with tetrahydropterin binding first to the free enzyme followed by binding of tyrosine. 5-Deaza-6 methyltetrahydropterin is a noncompetitive inhibitor versus tetrahydropterins and tyrosine. The effect of varying the concentration of tyrosine on the Ki value for 5-deaza-6-methyltetrahydropterin is consistent with the binding of this inhibitor to both the free enzyme and to an enzyme-dihydroxyphenylalanine complex. Dihydroxyphenylalanine also is a noncompetitive inhibitor versus tetrahydropterins and tyrosine; the effect of changing the fixed substrate is consistent with the binding of this inhibitor to both the free enzyme and to the enzyme-tetrahydropterin complex. The effect of pH on the Ki values was determined in order to measure the pKa values of amino acid residues involved in substrate binding. Tight binding of catechols requires that a group with a pKa value of 7.6 be deprotonated. Binding of 3-iodotyrosine involves two groups with pKa values of 7.5 and about 5.5, one of which must be protonated for binding. Binding of 5 deaza-6-methyltetrahydropterin requires that a group on the free enzyme with a pKa value of 6.1 be protonated. The Ki value for dihydroxyphenylalanine is relatively insensitive to pH, but the inhibition pattern changes from noncompetitive to competitive above pH 7.5, consistent with the measured pKa values for binding to the free enzyme and to the enzyme-tetrahydropterin complex. PMID- 2903150 TI - Fo portion of Escherichia coli H+-ATPase. Carboxyl-terminal region of the b subunit is essential for assembly of functional Fo. AB - Six chromosomal uncF mutants of Escherichia coli defective in the b subunit of H+ ATPase (156 amino acid residues) were identified (KF92, Met-1----Val; KF164, Gln 64----end; KF61 and KF144, Gln-104----end; KF138, Gln-106----end; and KF79, Gln 123----end). The membranes of all these mutants had low ATPase activities (less than 5% of that of the wild type), and no functional H+ pathway, although the truncated b subunits were integrated into these membranes. These findings suggest that about 30 carboxyl-terminal amino acid residues of the b subunit are essential for formation of the F1-binding site and H+ pathway. For examination of the role(s) of the carboxyl-terminal region(s) or residue(s) of the b subunit, recombinant plasmids carrying truncated uncF genes of various lengths were constructed by in vitro muta-genesis and introduced into a recA1 derivative of strain KF92 (Met-1----Val). Analyses of the membranes from the resulting strains demonstrated that almost the entire carboxyl-terminal region of the b subunit is necessary for formation of functional Fo, since loss of the carboxyl-terminal residue resulted in significant reduction of both F1 binding and H+ translocation, and loss of two or more residues abolished both activities completely. PMID- 2903151 TI - Differential translation of two distinct preprosomatostatin messenger RNAs. AB - Somatostatin (SRIF) is a 14-amino acid peptide hormone that is present in pancreatic islets and the brain where it is synthesized as a larger precursor, preprosomatostatin. In pancreatic islets of the anglerfish (Lophius americanus), there are two separate precursors, preproSRIF I and preproSRIF II, which give rise to SRIF-14 or an N-terminally extended form SRIF-28, respectively. Significantly higher levels of preproSRIF I compared to preproSRIF II are synthesized in pancreatic islets. We show here that preproSRIF II mRNA possesses an eight-nucleotide repeat (CCAGCAGA) which is present three times in its 5' noncoding region; this sequence is absent from preproSRIF I mRNA. Progressive deletion of these octameric repeats results in the concomitant enhancement of preproSRIF II mRNA translation in vitro. Furthermore, expression of native or 5' truncated preproSRIF II mRNA in non-islet tissue culture cells, using a retroviral expression vector, gave identical results to those obtained in vitro, indicating that differential translation was a function of the mRNA rather than the translation system. We propose that the octameric repeat sequence, or a subset of it, is responsible for attenuation of preproSRIF II mRNA translation. Since the differential translation of preproSRIF II mRNA was reproduced in widely divergent systems, this suggests that our results are not related to islet cell gene expression per se. Rather, it is possible they have general significance in that the 5'-repeat sequences may be recognized by putative trans-acting factors involved in the translational regulation of protein synthesis. PMID- 2903152 TI - Insulin regulates expression of the human growth hormone gene in transfected cells. AB - Insulin has been shown to inhibit rat growth hormone (GH) gene transcription. The effects of insulin were therefore tested on the expression of a transfected human GH gene. A 2.6-kilobase EcoRI fragment of the human GH gene was propagated in pUC18 and transfected by calcium-phosphate shock into HeLa and GC cells, respectively. Transfected cells grown in serum-free medium for 72 h expressed human GH measured by specific radioimmunoassay, incorporation of [35S] methionine into newly synthesized GH, and the presence of the appropriately sized protected transcripts seen after RNase protection assay. Immunoprecipitation analysis showed that insulin (0.7-7 nM) suppressed both the basal as well as the hydrocortisone (100 nM)-stimulated expression of newly synthesized 22-kDa GH in a dose-dependent fashion. Insulin (7 nM) also suppressed the basal and hydrocortisone-stimulated GH mRNA transcripts in these cells. Control nontransfected cells did not express human GH. Cells transfected with the truncated pOGH gene and pTKGH gene failed to respond to insulin treatment, whereas the human GH promoter was able to confer insulin responsiveness to the chloramphenicol acetyltransferase reporter gene. cis-Acting regulatory sequences residing on the 497-base pair 5'-flanking region of the human GH gene therefore appear to be a requirement for human GH gene response to the insulin signal. PMID- 2903153 TI - Structure of the gene encoding rat thyrotropin releasing hormone. AB - The gene encoding the hypothalamic peptide thyrotropin releasing hormone (TRH) was isolated from two rat genomic bacteriophage libraries. Southern blot analysis indicates that the gene is present as a single copy in the rat genome. The transcriptional unit is 2.6 kilobases in size and contains three exons interrupted by two introns of approximately 750 and 450 base pairs. Exon 1 encodes the 5'-untranslated region of the mRNA, exon 2 encodes the signal sequence and the majority of the amino-terminal peptide, and exon 3 encodes the remainder of the amino-terminal peptide, five copies of the TRH sequence, the carboxyl-terminal peptide, and the 3'-untranslated region of the mRNA. The general structure of the TRH gene resembles that of three other polypeptide hormone genes, preproopiomelanocortin, preproenkephalin A, and preproenkephalin B. Further sequence analysis revealed that characteristic promoter elements are present in the 5'-flanking region of the TRH gene. In addition, sequence homologies with the glucocorticoid receptor binding site, the GC box hexanucleotide, and a portion of the flanking region of the thyroid stimulating hormone beta-subunit gene were also identified. These upstream sequences may be important for the regulation of TRH gene expression. PMID- 2903154 TI - Evidence for a functional role for histidine in lysyl oxidase catalysis. AB - The pH-dependent kinetics of lysyl oxidase catalysis was examined for evidence of an ionizable enzyme residue which might function as a general base catalyzing proton abstraction previously shown to be a component of the mechanism of substrate processing by this enzyme. Plots of log Vmax/Km for the oxidation of n hexylamine versus pH yielded pKa values of 7.0 +/- 0.1 and 10.4 +/- 0.1. The higher pKa varied with different substrates, reflecting ionization of the substrate amino group. A van't Hoff plot of the temperature dependence of the lower pKa yielded a value of 6.1 kcal mol-1 for the enthalpy of ionization. This value as well as the pKa of 7.0 are consistent with those of histidine residues previously implicated as general base catalysts in enzymes. Incubation of lysyl oxidase with low concentrations of diethyl pyrocarbonate, a histidine-selective reagent, at 22 degrees C and pH 7.0 irreversibly inhibited enzyme activity by a pseudo first-order kinetic process. The inactivation of lysyl oxidase correlated with spectral and pH-dependent kinetic evidence for the chemical modification of 1 histidine residue/mol of enzyme, the pKa of which was 6.9 +/- 0.1, within experimental error of that seen in the plot of log Vmax/Km versus pH. Enzyme activity was restored by incubation of the modified enzyme with hydroxylamine, consistent with the ability of this nucleophile to displace the carbethoxy group from N-carbethoxyhistidine. The presence of the n-hexylamine substrate largely protected against enzyme inactivation by diethyl pyrocarbonate. These results thus indicate a functional role for histidine in lysyl oxidase catalysis consistent with that of a general base in proton abstraction. PMID- 2903155 TI - Peripheral and integral subunits of the tonoplast H+-ATPase from oat roots. AB - The subunit organization of the tonoplast H+-pumping ATPase from oat roots (Avena sativa L. var. Lang) was investigated. Tonoplast vesicles were treated with low ionic strength solutions (0.1 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer or 0.1 mM Na EDTA), carbonate, or a chaotropic reagent (KI), and then centrifuged to give a soluble fraction and a pellet. Treatments with low ionic strength solutions or KI resulted in 70-80% reduction in the membrane-associated ATPase activity, but did not affect the K+-stimulated pyrophosphatase activity. Polypeptides of 72, 60, and 41 kDa were solubilized from tonoplast vesicles by these wash treatments. These polypeptides reacted with polyclonal antibodies against the holoenzyme of tonoplast ATPase (anti-ATPase) and copurified with the tonoplast ATPase activity during gel filtration chromatography (Sepharose CL-6B). Mono-specific antibody against the 72- or 60-kDa polypeptide reacted with the solubilized 72- or 60-kDa polypeptide, respectively. However, the N,N [14C]dicyclohexylcarbodiimide-binding 16-kDa polypeptide and a 13-kDa polypeptide that also reacted with anti-ATPase and copurified with the tonoplast ATPase activity during gel filtration remained in the pellets after the wash treatments. We conclude that the 72- and 60-kDa polypeptides appear to be peripheral subunits of the tonoplast ATPase and that the 16-kDa polypeptide is probably embedded in the membrane bilayer. Additional subunits of the ATPase complex may include a 41 kDa (peripheral) and a 13-kDa (integral) polypeptide. Based on these results, a working model of the tonoplast ATPase analogous to the F1F0-ATPase is proposed. PMID- 2903156 TI - Properties of chloroplast F1-ATPase partially modified by 2-azido adenine nucleotides, including demonstration of three catalytic pathways. AB - Previous investigations on the distribution of [18O]Pi isotopomers formed by hydrolysis of [gamma-18O]ATP by the chloroplast F1-ATPase (CF1) showed that a single reaction pathway is used by all participating sites and that the pathway is modulated by ATP concentration as expected for cooperative interactions between catalytic sites. Such oxygen exchange measurements have been applied to CF1 modified at a single catalytic or noncatalytic site by 2-azido adenine nucleotides. When less than one catalytic or one noncatalytic site per enzyme is modified, hydrolysis occurs in part by the pathway of the unmodified enzyme plus at least one additional pathway at 200 microM and two additional pathways at 4 microM [gamma-18O]ATP. Thus, three sites are potentially catalytically active. The two new pathways shown by the derivatized enzyme logically can arise from nonidentical interactions of the remaining two underivatized beta subunits with the derivatized beta subunit. Reversals of bound ATP cleavage before Pi is released are increased, and the amount of product formed by the new pathways is changed when the ATP concentration is lowered. These modulations must result from the behavior of two remaining active catalytic sites rather than of one catalytic and one regulatory site. When the CF1 is derivatized more extensively, the original catalytic pathway is lost, and two catalytic pathways that do not show modulation by ATP concentration are found. The remaining beta subunits now have weak but independent catalytic capacity. In addition, the enzyme is no longer activated by Ca2+, loses MgGTPase activity, and is much less sensitive to azide. PMID- 2903157 TI - The transforming growth factor-beta receptor type III is a membrane proteoglycan. Domain structure of the receptor. AB - The transforming growth factor-beta (TGF-beta) receptor type III is a low abundance cell surface component that binds TGF-beta 1 and TGF-beta 2 with high affinity and specificity, and is present in many mammalian and avian cell types. Type III TGF-beta receptors affinity-labeled with 125I-TGF-beta migrate in sodium dodecyl sulfate-polyacrylamide electrophoresis gels as diffuse species of 250-350 kDa. Here we show that type III receptors deglycosylated by the action of trifluoromethanesulfonic acid yield affinity-labeled receptor cores of 110-130 kDa. This marked decrease in molecular weight is also achieved by combined treatment of type III receptors with heparitinase and chondroitinase ABC. Digestion of receptor-linked glycosaminoglycans by treatment of intact cell monolayers with heparitinase and chondroitinase does not prevent TGF-beta binding to the type III receptor core polypeptide and does not release the receptor polypeptide from the membrane. The type III TGF-beta receptor binds tightly to DEAE-Sephacel and coelutes with cellular proteoglycans at a characteristically high salt concentration. Thus, the type III TGF-beta receptor has the properties of a membrane proteoglycan that carries heparan and chondroitin sulfate glycosaminoglycan chains. The binding site for TGF-beta appears to reside in the 100-120-kDa core polypeptide of this receptor. The type III receptor is highly sensitive to cleavage by trypsin. Trypsin action releases the glycosaminoglycan containing domain of the receptor leaving a 60-kDa membrane-associated domain that contains the cross-linked ligand. A model for the domain structure of the TGF-beta receptor type III is proposed based on these results. PMID- 2903158 TI - Developmental regulation and tissue-specific expression of the human muscle creatine kinase gene. AB - To define mechanisms regulating expression of M creatine kinase, the human gene including 5'-flanking DNA was cloned, characterized, and partially sequenced. The gene contains 8 exons interrupted by 7 introns spanning 17.5 kilobase pairs of DNA. The intron-exon splice sites were identified and conform to the GT-AG consensus rule. The TATA and CAAT boxes are located at positions -31 and -56 upstream of the transcription start site as determined by primer extension. The 5'-untranslated region is interrupted with the translation start codon located in the second exon. To determine whether sequences within the 5'-upstream DNA confer tissue-specific expression and developmental regulation, constructs containing 2620 base pairs of human M creatine kinase 5'-flanking DNA fused upstream of the chloramphenicol acetyltransferase gene in the promoterless plasmid pSVO-CAT were transfected into cultured C2C12 myoblasts. There was 17-fold induction of chloramphenicol acetyltransferase activity during differentiation as C2C12 myoblasts fused to form myotubes. The M creatine kinase fusion construct was not expressed in transfected nonmuscle cell lines, COS-7 and NIH/3T3. Thus, cis acting sequences within 2620 base pairs of the cap site are sufficient to direct developmental regulation and tissue-specific expression of the human M creatine kinase gene. PMID- 2903159 TI - A surface component on GH3 pituitary cells that recognizes transforming growth factor-beta, activin, and inhibin. AB - We have examined the ability of various forms of activin and inhibin, which are structurally related to transforming growth factor-beta (TGF-beta), to interact with various types of cell surface TGF-beta binding sites. Activin AB, inhibin A, and inhibin B were unable to compete with 125I-TGF-beta 1 for binding to the TGF beta receptor types I, II, or III that coexist in human skin fibroblasts, rat liver epithelial cells, and mink lung epithelial cells. In contrast, activins and inhibins effectively competed for TGF-beta 1 binding to GH3 rat pituitary tumor cells. Binding of TGF-beta 1 to GH3 cells was mediated by about 2700 sites/cell with a Kd = 90 pM. Affinity labeling of these GH3 binding sites by cross-linking to 125I-TGF-beta 1 yielded 70-74-kDa labeled complexes distinct from previously identified TGF-beta binding components. Labeling of these 70-74-kDa components with 125I-TGF-beta 1 was inhibited by TGF-beta 1, TGF-beta 2, activin AB, and inhibin B at concentrations in the high picomolar to low nanomolar range, but it was not significantly affected by other polypeptide hormones and growth factors tested. The 70-74-kDa labeled GH3 components represent a novel type of cell surface TGF-beta binding protein that is unique in its ability to recognize various other members of the TGF-beta family of bioactive polypeptides. PMID- 2903160 TI - Molecular cloning of the beta-subunit of a possible non-F0F1 type ATP synthase from the acidothermophilic archaebacterium, Sulfolobus acidocaldarius. AB - The gene which encodes the beta subunit of the novel membrane-associated ATPase has been identified and characterized. The beta subunit, which is most likely the soluble part of the non-F0F1 type H+-ATPase, was obtained from the archaebacterium, Sulfolobus acidocaldarius. In terms of its location, it follows just after the gene for its alpha subunit. It is comprised of 1398 nucleotides, corresponding to a protein of 465 amino acids, and the consensus sequence in the nucleotide binding proteins is poorly conserved. Together with previously described results, the distant homology of the S. acidocaldarius ATPase alpha and beta subunits when compared to those of F0F1-ATPases indicates that this archaebacterial ATPase belongs to an ion-translocating ATPase family uniquely different than F0F1-ATPases even if S. acidocaldarius ATPase and F0F1-ATPases have been derived from a common ancestral ATPase. PMID- 2903161 TI - Persulfide generated from L-cysteine inactivates tyrosine aminotransferase. Requirement for a protein with cysteine oxidase activity and gamma-cystathionase. AB - Liver cytosols contain factors that produce an inhibitor of tyrosine aminotransferase and other enzymes when incubated with L-cysteine or L-cystine. Cystine-dependent inactivation was caused by cystathionase and required pyridoxal 5'-phosphate, but a second protein was needed to reconstitute cysteine-dependent inactivation. A cytosolic protein was isolated that oxidized free cysteine and brought about inactivation of tyrosine aminotransferase when coincubated with cystathionase. Hematin also oxidized cysteine, which led to cysteine-dependent inactivation of tyrosine aminotransferase in the presence of cystathionase. The inactivation of tyrosine aminotransferase involved three steps: initial oxidation of cysteine to form cystine; desulfuration of cystine catalyzed by cystathionase to form the persulfide, thiocysteine; and reaction of thiocysteine (or products of its decomposition) with proteins to form protein-bound sulfane. Since dithiothreitol reactivated tyrosine aminotransferase, the sulfane probably inactivated the enzyme by oxidation of thiol groups. The present results do not indicate whether the cysteine oxidase activity is enzymatic nor do they prove which form of polysulfide inactivates tyrosine aminotransferase. Reduced glutathione greatly slowed the rates at which sulfane accumulated and at which tyrosine aminotransferase was inactivated. Incubation of DL-cystathionine with liver cytosols led to formation of cysteine, which was oxidized and cleaved to form persulfide, and caused inactivation of tyrosine aminotransferase. Thus, sulfane sulfur that is generated by an enzyme of the transulfuration pathway inactivates a transaminase by nonselective oxidation of enzyme-bound thiol groups. PMID- 2903162 TI - Differentiation-induced gene expression in 3T3-L1 preadipocytes. Characterization of a differentially expressed gene encoding stearoyl-CoA desaturase. AB - Previous studies have shown that differentiation of 3T3-L1 preadipocytes leads to the activation of transcription of an unidentified gene which encodes a 4.9 kilobase (kb) mRNA. Several cDNAs that include the complete sequence of this mRNA were obtained and used to isolate and characterize the gene. Analysis of the nucleotide and amino acid sequences of both cDNA and genomic clones revealed that the gene encodes the mouse stearoyl-CoA desaturase (SCD), an enzyme known to be expressed upon differentiation of 3T3-L1 preadipocytes. The predicted amino acid sequence (355 residues) of the mouse 3T3-L1 adipocyte SCD exhibits 92% identity to that of the rat liver SCD. There is also a high degree of nucleotide sequence identity between the mouse and rat mRNAs in their unusually long approximately 3.5-kb 3'-untranslated regions. Mice fed a diet containing unsaturated triacylglycerides express SCD mRNA only in adipose tissue, whereas mice starved and refed a fat-free diet, express SCD mRNA in both liver and adipose tissue. The mouse gene for the desaturase spans approximately 15 kb and contains 6 exons and 5 introns with all intron-exon junctions conforming to the GT/AG splicing rule. As determined by S1 nuclease mapping and primer extension analysis, the transcriptional initiation site maps 152 nucleotides upstream from the initiation methionine codon. A canonical promoter "TATA" box is located 30 base pairs upstream of the Cap site. A typical "CCAAT" box sequence is not present in the adjacent 5'-flanking region; however, there is a GC-rich sequence (at nucleotide 215) similar to the binding site for the nuclear transcription factor Sp1. Upstream from the transcriptional initiation site are elements with homology (approximately 75%) to the putative fat-specific transcriptional element FSE2 and core consensus sequences for cAMP and glucocorticoid regulatory elements. A chimeric construct, containing 363 base pairs of 5'-flanking sequence and 30 nucleotides of 5'-untranslated sequence of the mouse SCD gene ligated to the bacterial chloramphenicol acetyltransferase gene, was transfected into 3T3-L1 cells. When cells were induced to differentiate into adipocytes, expression of the SCD chloramphenicol acetyltransferase gene increased approximately 63-fold, suggesting that the SCD promoter region contains elements that mediate the response to adipogenic agents which induce differentiation. PMID- 2903163 TI - Functional domains of epsilon subunit of Escherichia coli H+-ATPase (F0F1). AB - Mutants of the uncC gene for the epsilon subunit (138 amino acid residues) of Escherichia coli H+-ATPase were isolated: strain KF53 (Gln-72----end) and KF148(SD-) (two base substitutions in the Shine-Dalgarno sequence, GGAGG--- AAAGG). These strains did not have F1 bound to membranes and were unable to grow by oxidative phosphorylation. A series of plasmids carrying truncated uncC genes were constructed and introduced into strain KF148(SD-). Analyses of KF148(SD-) cells with different plasmids indicated that the amino-terminal fragment of the epsilon subunit of 78-80 amino acid residues was capable of forming active membrane-bound F1-ATPase, whereas that of 73 residues was not, indicating that the carboxyl-terminal half of the epsilon subunit is not necessary for the active enzyme. Furthermore, results indicated that residues between 73 and 78-80 may have a critical role(s) in binding F1 to F0. Truncated epsilon subunits of 80 and 93 residues were identified in purified F1 from cells carrying the respective uncC genes, and only the latter subunit had intrinsic activity to inhibit ATPase of F1, suggesting that residues between 80 and 93 are essential for the inhibitory activity. PMID- 2903164 TI - Cloning of cDNA encoding a 32-kDa protein. An accessory polypeptide of the H+ ATPase from chromaffin granules. AB - The purified H+-ATPase from chromaffin granules is composed of several polypeptides, one of which has an apparent molecular weight of 39,000. Immunoblots with the antibody against this protein and various membrane preparations showed that similar or even identical polypeptides may be associated with the H+-ATPases from synaptic vesicle, kidney microsomes, and lysosomes. A cDNA library was constructed from bovine adrenal medulla, and the cDNA encoding the polypeptide was isolated and sequenced. Search in DNA and protein data banks revealed no significant homology to known genes. Hydrophobicity plot revealed no obvious transmembrane segments with the exception of one stretch of hydrophobic and neutral amino acid starting at leucine 16. The cDNA was shown to encode the entire polypeptide by the virtue of an amino acid sequence corresponding to the N terminus of the open reading frame and by subunit and site-specific antibodies. The cDNA was cloned into an expression vector, transcribed by T7 polymerase, and translated by reticulocyte lysate. Even though the cDNA encodes a protein with a molecular weight of 31,495, the translation product comigrated on sodium dodecyl sulfate gels with the subunit of the purified H+-ATPase. In line with several other subunits of vacuolar H+-ATPases, no signal sequence was detected in the translated gene. Northern blots revealed the presence of a single mRNA of about 1.6 kb in bovine adrenal medulla. However, liver, lung, and kidney may contain additional mRNA of about 1.7 kb. PMID- 2903165 TI - Subdural abscess associated with halo-pin traction. AB - Osteomyelitis and intracranial abscess are among the most serious complications that have been reported in association with the use of the halo device. The cases of five patients who had formation of an intracranial abscess related to the use of a halo cervical immobilizer are described. All of the infections resolved after drainage of the abscess, debridement, and parenteral administration of antibiotics. Meticulous care of the pin sites is essential to avoid this serious complication. Additionally, since all of the infections were associated with prolonged halo-skeletal traction, this technique should be used with caution and with an awareness of the possible increased risks of pin-site infection and of formation of a subdural abscess. PMID- 2903167 TI - Pharmacologic treatment of angina: nitrate tolerance. PMID- 2903166 TI - Changes in cyclin/proliferating cell nuclear antigen distribution during DNA repair synthesis. AB - UV irradiation of quiescent human fibroblasts immediately triggers the appearance of the nuclear protein cyclin/proliferating cell nuclear antigen (PCNA) as detected by indirect immunofluorescent staining after methanol fixation. This was found to be independent of new synthesis of cyclin/PCNA by two-dimensional gel analysis and cycloheximide treatment. The intensity of the immunofluorescent staining of cyclin/PCNA observed in UV-irradiated cells corresponded with the UV dose used and with the DNA repair synthesis detected by autoradiography. The nuclear staining remains as long as DNA repair activity is detected in the cells. By extracting the UV-irradiated quiescent cells with Triton X-100 and fixing with formaldehyde, it was possible to demonstrate by indirect immunofluorescence rapid changes in the cyclin/PCNA population after irradiation, a small proportion (5 10%) of which is tightly associated to the nucleus as determined by high salt extraction. By incubating at low temperature and depleting the ATP pools of the cells before UV irradiation, we have demonstrated that the changes in cyclin/PCNA distribution observed involve at least two different nuclear associations. PMID- 2903168 TI - Preoperative treatment of acromegaly with long-acting somatostatin analog SMS 201 995: shrinkage of invasive pituitary macroadenomas and improved surgical remission rate. AB - Ten patients with previously untreated acromegaly and invasive pituitary macroadenomas were treated with the long-acting somatostatin analog SMS 201-995 (Sandoz) for 3-30 weeks before transsphenoidal or subfrontal pituitary adenomectomy. Preoperatively, treatment with SMS 201-995 reduced mean 24-h plasma GH concentrations from 8.5-66.7 to below 4.6 micrograms/L in eight patients and by 60-80% in the remaining two patients. Pituitary tumor size decreased 20-54%. Morphologically, the tumors showed decreased total cell, cytoplasmic, and nuclear areas; varying degrees of perivascular fibrosis; and dense granularity. Postoperatively, plasma GH and insulin-like growth factor I concentrations fell into the normal range, and GH dynamics became normal in eight patients. In the remaining two patients mild GH hypersecretion persisted after surgery (mean fasting and random plasma GH, 6.1 and 7.9 micrograms/L), and in one of them GH secretion became normal 1 yr after pituitary irradiation. Thus, preoperative administration of SMS 201-995 consistently induced shrinkage of GH-producing pituitary tumors, and the apparent remission rate was high in the treated patients. PMID- 2903169 TI - Alpha 2-adrenoceptor blockade does not enhance glucose-induced insulin release in normal subjects or patients with noninsulin-dependent diabetes. AB - Studies with phentolamine, an alpha-adrenergic antagonist, in normal subjects and diabetic patients have indicated that insulin secretion may be inhibited by tonic alpha-adrenergic stimulation of pancreatic B-cells. We evaluated, with the use of the highly selective alpha 2-adrenoceptor antagonist idazoxan, the role of alpha 2-adrenergic receptors in the regulation of glucose-induced insulin secretion. A glucose infusion test (GIT) was performed after the administration of idazoxan or placebo in normal men (n = 15) and men with noninsulin-dependent diabetes mellitus (n = 6). The normal men were divided into two groups on the basis of high (n = 8) and low (n = 7) insulin responses to prior GITs. The blood glucose and plasma insulin and C-peptide responses to the GIT were similar after idazoxan (40 mg, orally) or placebo treatment in all three groups, although the responses differed among the groups. In the diabetic group iv administration of idazoxan 20 min before the GIT did not alter the insulin response to the GIT. We conclude that alpha 2-adrenergic blockade does not affect glucose-induced insulin secretion in normal men, nor does it improve the impaired first phase of insulin secretion in low insulin responders and noninsulin-dependent diabetes mellitus patients. Phentolamine probably stimulates insulin secretion by a mechanism not involving alpha 2-adrenergic receptors directly. PMID- 2903170 TI - The effects of sodium valproate on plasma somatostatin and insulin in humans. AB - To determine the role of gamma-aminobutyric acid (GABA) in islet tissue, sodium valproate (1600 mg/day) was administered for 6 days to 10 normal subjects and 1 patient with a somatostatinoma. Plasma valproate concentrations reached a steady state by the third day accompanied by elevation of plasma GABA concentrations. Sodium valproate administration resulted in a 40% decrease in plasma somatostatin concentrations in the normal subjects and a 63% decrease in the somatostatinoma patient, respectively, compared to the response to placebo. Plasma C-peptide concentrations did not change in any subject. Fasting blood glucose levels decreased in the somatostatinoma patient during sodium valproate administration. These results suggest that endogenous GABA may play some role in the release of somatostatin, but not in the release of insulin. PMID- 2903172 TI - Organization of human homeobox genes. AB - The chromosomal localization of 17 human homeoboxes and the predicted primary sequence of the encoded homeodomains is reported. These homeoboxes are clustered in four complex HOX loci on chromosomes 2, 7, 12 and 17. Although the identification of human homeoboxes has not been completed, existing data permit preliminary conclusions on the origin and evolution of these complex loci to be drawn. The homeo-domains of one HOX locus can be unambiguously aligned to the homeodomains of the other HOX loci, so that corresponding homeodomains in all loci can share the maximal peptide sequence identity. This one-to-one correspondence of individual homeodomains in different chromosomal loci suggests the hypothesis of large-scale duplications of a single complex locus and subsequent spreading in different chromosomes. The existence of an ancestral complex locus might have predated the divergence of the arthropod/annelid and vertebrate evolutive lineages. PMID- 2903171 TI - Comparison of the sensitivity of growth hormone secretion to somatostatin in vivo and in vitro in acromegaly. AB - Somatostatin (SRIH) sensitivity in acromegaly was evaluated in vivo by comparing the inhibition of GHRH (1 microgram/kg, iv)-stimulated GH secretion in eight acromegalic and six normal subjects. A SRIH infusion (50 micrograms/h) that inhibited the mean plasma GH response to GHRH by 74 +/- 5% (+/- SE) in normal subjects had no significant effect in the acromegalic patients. However, when two acromegalic patients in whom SRIH had no suppressive effect were excluded from the analysis, the effect of SRIH in the other six (82 +/- 7%) was comparable to that in the normal subjects. Within the acromegalic group, the percent suppression of basal and GHRH-stimulated GH secretion was inversely correlated with both basal plasma GH (r = -0.751; P = 0.03 and r = -0.727; P = 0.04, respectively) and insulin-like growth factor I (r = -0.800; P = 0.02 and r = 0.727; P = 0.04, respectively) concentrations. The in vitro sensitivity to SRIH was studied in pituitary adenomas from five of the acromegalic patients in 3- to 4-day monolayer cultures of dispersed cells. The SRIH IC50 values were lowest in the tumors (8.6-44 pmol/L) from the three patients who had in vivo SRIH sensitivity (suppression of GHRH-stimulated GH secretion) comparable to that in the normal subjects. The IC50 values were higher in the tumors (150 and 21,000 pmol/L) from the two patients that were least responsive to SRIH in vivo. These results indicate that there is considerable variability of SRIH sensitivity in patients with acromegaly. Although the role of this defect in the pathogenesis of acromegaly is uncertain, it may be an important determinant in the degree of elevation of plasma GH levels. PMID- 2903173 TI - Vibrio cholerae non-O1: production of cell-associated hemagglutinins and in vitro adherence to mucus coat and epithelial surfaces of the villi and lymphoid follicles of human small intestines treated with formalin. AB - Clinically isolated Vibrio cholerae non-O1 strains produced more cell-associated hemagglutinins (HAs) on colonization factor antigen agar after ca. 3 h than after ca. 20 h of incubation at 37 degrees C. A high cell-associated HA producer variant of strain TVN-318, grown for 3 h at 37 degrees C, was entrapped in a native mucus coat covering the human ileal mucosa and displayed a striking ability to adhere to the surface of a Formalin-treated mucus coat, in contrast to a poor cell-associated HA producer variant of TVN-318, grown for 20 h at 37 degrees C. Adherence to the Formalin-treated human mucus coat was confirmed with all of the strains tested. V. cholerae non-O1 strains also possessed the ability to adhere to the epithelial surfaces of Formalin-treated human and rabbit ileal or jejunal villi, as well as human lymphoid follicles, in proportion to cell associated HA levels. The epithelial surface of the lymphoid follicles provided most of the adherence sites for V. cholerae non-O1 strains under the test conditions. We conclude that a mucus coat covering the human small intestinal mucosa is a primary adherence target for V. cholerae non-O1 strains in human intestinal infections and that cell-associated HAs have at least a partial role in the adherence of V. cholerae non-O1 strains to the human small intestine, suggesting a potential role for V. cholerae non-O1 strains in an oral live vaccine. PMID- 2903174 TI - Monoclonal antibody-based sandwich enzyme-linked immunosorbent assay for detection of Bordetella pertussis filamentous hemagglutinin. AB - Hybrid cell lines producing monoclonal antibodies against Bordetella pertussis filamentous hemagglutinin (FHA) were established. The specificity of the antibodies was ascertained by enzyme-linked immunosorbent assay (ELISA), sandwich ELISA, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by electroblotting. The monoclonal antibody-based sandwich ELISA was developed for detection of B. pertussis FHA. The assay had a detection limit of B. pertussis FHA in concentrations ranging from 7 to 15 ng/ml. The assay was also able to detect whole B. pertussis, Bordetella parapertussis, and Bordetella bronchiseptica bacteria. No cross-reactions were observed with strains of Branhamella catarrhalis, Neisseria meningitidis, Haemophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila, Streptococcus miteor, or Streptococcus pneumoniae. The monoclonal antibodies might be useful for the detection of soluble antigens and whole bacteria in clinical samples and for studies of the immunochemical structure of B. pertussis FHA. PMID- 2903175 TI - Detection of genomic variation in Providencia stuartii clinical isolates by analysis of DNA restriction fragment length polymorphisms containing rRNA cistrons. AB - Chromosomal DNA from 26 strains of Providencia stuartii isolated mainly in hospitals in the United Kingdom and reference strains of P. stuartii, P. rustigianii, and Proteus vulgaris were digested with the restriction endonucleases EcoRI and HindIII. After electrophoresis in agarose gels, the fragments were subjected to Southern blot hybridization analysis with a biotin labeled cDNA probe transcribed from a mixture of 16S and 23S rRNA from P. stuartii NCTC 11800T. The pattern of bands (the rDNA fingerprint), which depended on restriction fragment length polymorphisms containing rRNA genes, was used as a measure of minor genomic variation within and between species. The P. stuartii clinical isolates had similar total digest patterns, but the rDNA fingerprints revealed some heterogeneity between strains, with EcoRI digests providing better strain discrimination than HindIII. Such rDNA fingerprints comprised between five and seven bands with sizes in the range of 5 to 28 kilobases. The 11 different EcoRI patterns were compared by numerical analysis, and several groups or subgroups of strains were identified. Over half (15 of 26) of the urease-negative isolates (subgroups Aa and Ab) had patterns that differed only by the presence or absence of a 25-kilobase band. Urease-negative strains from other clinical material were more heterogeneous in their patterns. No correlation was apparent between strain pattern group and urease production or geographic location of isolate. The P. stuartii rDNA fingerprints were quite distinct from those of allied Providencia and Proteus species and provided a more sensitive measure of minor genomic differences than total DNA digests did. PMID- 2903176 TI - Restriction fragment length polymorphisms of the DNA of selected Naegleria and Acanthamoeba amebae. AB - Fourteen strains of Naegleria fowleri, two strains of N. gruberi, and one strain each of N. australiensis, N. jadini, N. lovaniensis, Acanthamoeba sp., A. castellanii, A. polyphaga, and A. comandoni isolated from patients, soil, or water were characterized by restriction fragment length polymorphisms. Total cellular DNA (1 microgram) was digested with either HindIII, BglII, or EcoRI; separated on agarose gels; and stained with ethidium bromide. From 2 to 15 unusually prominent repetitive restriction fragment bands, totaling 15 to 50 kilobases in length and constituting probably more than 30% of the total DNA, were detected for all ameba strains. Each species displayed a characteristic pattern of repetitive restriction fragments. Digests of the four Acanthamoeba spp. displayed fewer, less intensely staining repetitive fragments than those of the Naegleria spp. All N. fowleri strains, whether isolated from the cerebrospinal fluid of patients from different parts of the world or from hot springs, had repetitive restriction fragment bands of similar total lengths (ca. 45 kilobases), and most repetitive bands displayed identical mobilities. However, polymorphic bands were useful in identifying particular isolates. Restriction fragment length polymorphism analysis generally was consistent with taxonomy based on studies of infectivity, morphology, isoenzyme patterns, and antibody reactivity and suggests that this technique may help classify amebae isolated from clinical specimens or from the environment. PMID- 2903177 TI - Effects of transport temperature and medium on recovery of Bordetella pertussis from nasopharyngeal swabs. AB - We compared relative recoveries of Bordetella pertussis from simulated nasopharyngeal (NP) specimens incubated in three separate transport media at different temperatures. Transport media included one-half-strength Regan-Lowe (RL.5), Regan-Lowe with one-half-strength agar (RL.5A), and buffered charcoal yeast extract agar supplemented with alpha-ketoglutarate, lincomycin, and anisomycin (BCYE alpha LA). For each transport medium, recovery of B. pertussis was least efficient after storage at 25 degrees C. The highest recovery of B. pertussis from a mixed culture was achieved with RL.5 at 4 degrees C. Overall, RL.5 and RL.5A were comparable as transport media whether held at 4 or 25 degrees C, but fewer organisms were recovered from BCYE alpha LA. In addition, Regan-Lowe (RL), Bordet-Gengou, and cyclodextrin media were compared as primary isolation media for recovering B. pertussis from simulated NP swabs held at 4 and 35 degrees C in RL.5 medium. The highest recovery of B. pertussis was obtained on RL primary isolation medium. Bordet-Gengou medium recovered only 80% and cyclodextrin medium recovered less than 60% of the numbers recovered on RL medium. Based on these results, refrigeration (4 degrees C) of NP swabs shipped in RL.5 transport medium and using RL as the primary isolation medium are recommended for recovering B. pertussis from swab specimens. PMID- 2903178 TI - Evaluation of serologic assays for diagnosis of whooping cough. AB - An enzyme-linked immunosorbent assay (ELISA) for the immunoglobulin G (IgG), IgM, and IgA response to Bordetella pertussis filamentous hemagglutinin (FHA) and pertussis toxin (PT) and a neutralization test (NT) in a microplate tissue culture assay for neutralizing antibodies to PT were evaluated in paired sera from 90 patients with culture-confirmed pertussis. Eighty patients were children (age, less than 15 years), and 6 of 80 children had been immunized with three doses of diphtheria-tetanus-pertussis vaccine as infants. A significant titer rise (greater than or equal to twofold), determined by ELISA, of IgG, IgM, and IgA to FHA was recorded in 75 (83%), 28 (31%), and 47 (52%) of the patients, respectively. A significant titer rise to PT in IgG was found in 83 (92%), IgM in 29 (32%), and IgA in 44 (49%) of the patients. A significant titer rise to FHA or PT in IgG was found in 88 (98%) of the patients, in combination with a significant rise in the titer of IgA to FHA. These data were obtained in a single serum dilution of 1:500. Titrations performed later showed that the titer rise to FHA in IgG was a mean of 6.5-fold, which was significantly lower than the mean 67.0-fold rise in IgG to PT (P less than 0.001). The mean titer of IgG to FHA in convalescent-phase serum was 270, which was also significantly lower than the mean PT titer of 2,943 (P less than 0.001). A significant rise (greater than or equal to fourfold) in PT titer by NT was found in 58 of 83 (70%) of the patients. The NT was significantly less sensitive than the ELISA for the determination of the IgG titer to PT ( P< 0.001). Results showed that a 100% (90 of 90) sensitivity in terms of titer rises was achieved in the serologic diagnosis of pertussis by ELISA in a single-point determination of the IgG and IgA responses to FHA and of the IgG response to PT. PMID- 2903179 TI - Demonstration of the production and physiological role of insulin-like growth factor II in rat thyroid follicular cells in culture. AB - Insulin-like growth factors (IGFs) are potent mitogens for FRTL5 rat thyroid follicular cells. IGFs also synergize the independent mitogenic effects of thyrotropin-stimulating hormone (TSH) and other agents that increase intracellular AMP concentration. We examined whether FRTL5 cells and M12 cells, a TSH-independent mutant cell line derived therefrom, secrete IGF that regulates the growth of rat thyroid follicular cells. Immunoreactive IGF-II, but not IGF-I, was found in media conditioned by FRTL5 cells; media from M12 cells contained four- to fivefold higher concentrations. Medium conditioned by FRTL5 and M12 both stimulated [3H]thymidine incorporation in FRTL5 and amplified the mitogenic effects of TSH. M12-conditioned medium was more potent than FRTL5-conditioned medium. Sm-1.2, a monoclonal antibody that recognizes IGF-I and IGF-II but not insulin, inhibited basal DNA synthesis in FRTL5 and M12 cells and the mitogenic effects in FRTL5 of agents that are synergized by IGF, such as TSH, forskolin, Bt2cAMP, and Graves'-IgG. Sm-1.2 did not inhibit the mitogenic response to insulin. Thus, rat insulin-like growth factor II (rIGF-II) is an autocrine growth factor that regulates FRTL5 growth, in part by amplifying the mitogenic response to TSH. Results with M12 cells raise the possibility that endogenous rIGF-II may partially mediate the TSH-independent growth of these cells. PMID- 2903180 TI - Recognition of an endothelial determinant for CD 18-dependent human neutrophil adherence and transendothelial migration. AB - Human neutrophil (PMN) attachment to human umbilical vein endothelial cells (HUVEC) was evaluated in vitro using two MAbs, R6-5-D6 and RR1/1, that recognize intercellular adhesion molecule-1 (ICAM-1), and one MAb, TS1/18, that recognizes CD18. Pretreatment of the HUVEC with anti-ICAM-1 MAbs produced greater than 50% inhibition of attachment to HUVEC, and IL-1 (0.5 U/ml)- or lipopolysaccharide (LPS) (10 ng/ml)-stimulated HUVEC, and greater than 99% inhibition of f-Met-Leu Phe (0.5 nM) enhanced adherence. Anti-ICAM-1 MAbs also inhibited by greater than 85% the transendothelial migration induced by 4-h IL-1 (0.5 U/ml) and LPS (10 ng/ml) activation of the HUVEC. That these effects involved a CD18-dependent mechanism is supported by the following results: pretreatment of PMN with TS1/18 produced the same degree of inhibition of attachment and migration as seen with R6-5-D6. In addition, the use of both MAbs together did not further increase the inhibition of cell attachment to stimulated HUVEC. The attachment of PMN from patients with CD18 deficiency to stimulated HUVEC was not reduced by R6-5-D6, and both R6-5-D6 and TS1/18 revealed the same time course for appearance and disappearance of an adherence component on stimulated HUVEC not blocked by either MAb. These results demonstrate that attachment and transendothelial migration of PMN in vitro depend substantially on both CD18 on the PMN and ICAM-1 on the endothelial cell. PMID- 2903181 TI - Genetic evidence from two families that the apolipoprotein B gene is not involved in abetalipoproteinemia. AB - Abetalipoproteinemia (ABL) is a recessive disorder in which affected individuals have extremely low or undetectable levels of serum apo B-containing lipoproteins. Using restriction fragment length polymorphisms, we have studied two families, each with two children with classical ABL born of normal parents. In each of these families, the two affected children have inherited different apo B alleles from at least one parent, whereas the siblings would be anticipated to share common alleles if this disorder were due to an apo B gene mutation. This linkage study shows that in these families, the apo B gene is discordant with ABL and therefore the disorder is caused by a defect in another gene, which is important for the normal synthesis or secretion of apo B-containing lipoproteins from both the liver and intestine. PMID- 2903182 TI - Protracted tinnitus after discontinuation of long-term therapeutic use of benzodiazepines. AB - The presence of protracted tinnitus after discontinuation of long-term therapeutic doses of diazepam (less than or equal to 30 mg/day) is described in three patients. In one of these patients, the association of the tinnitus appearance with the drug discontinuation was documented in a double-blind, randomized, crossover single case study. Objective confirmation of drug use or of abstinence was performed by obtaining plasma benzodiazepine concentrations. The findings provide further documentation that sensory disturbances of short- and long-term duration are among the most distinctive clinical features of the benzodiazepine withdrawal syndrome. PMID- 2903183 TI - Bromocriptine sensitization of neuroleptic-induced acute dystonia. PMID- 2903184 TI - Neuroendocrine side effects of neuroleptics: comment. PMID- 2903185 TI - Outcome of a low dose neuroleptic treatment strategy. PMID- 2903186 TI - Cutaneous light microscopic and ultrastructural changes in a fatal case of jellyfish envenomation. AB - A 5-year-old male suffered fatal envenomation from a jellyfish subsequently identified as Chironex fleckeri. Contact with the tentacles of the jellyfish had produced characteristic whiplash-like weals on the skin. At autopsy, skin from these areas was taken and later studied by light microscopy and electron microscopy. Both studies identified numerous nematocysts penetrating the epidermis and papillary dermis in the region of the sting. PMID- 2903187 TI - Comparison between the effects of aging on antagonist and agonist interactions with beta-adrenergic receptors on human mononuclear and polymorphonuclear leukocyte membranes. AB - Age-related differences in the binding properties of beta-adrenergic receptors on lymphocyte membranes isolated from healthy individuals have been reported. The purpose of the present studies was to determine whether or not beta receptors on polymorphonuclear leukocyte (PMN) membranes showed similar age-related changes. Plasma Percoll gradients were used to isolate PMN and mononuclear leukocyte (MN) cells from blood drawn in the supine position from young (25-34 years) and elderly (60-76 years) healthy volunteers. Both blood pressures and plasma norepinephrine levels were significantly elevated in the elderly subjects. Saturation analysis with [125I]-(-) iodopindolol (IPIN) showed a 2.5-fold higher density of beta 2 receptors on the MN, but not PMN, membranes from the elderly. Neither the affinities of the receptor for IPIN or the agonist isoproterenol, nor the GTP-induced shift in agonist affinity, differed with subject age in either cell type. These results suggest that subpopulations of MN cells on which beta adrenergic receptors are localized may increase in the elderly and that it is important to measure receptor properties on a more homogeneous leukocyte population such as PMN cells or subpopulations of MN cells as a function of aging. PMID- 2903188 TI - Olsalazine and sulfasalazine allergy. PMID- 2903189 TI - Vasovagal reactions to cardiovascular drugs: the first dose effect. PMID- 2903190 TI - Renal effects of fenoldopam in refractory hypertension. AB - Fenoldopam, a dopamine-1 (D1) agonist, was administered by a 6-h intravenous infusion to patients with refractory hypertension [diastolic blood pressure (DBP) greater than 115 mmHg while on triple therapy] in order to achieve a fall in DBP of 30 mmHg. The evolution of blood pressure, heart rate, glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume, renal excretion of sodium, potassium, chloride, calcium, uric acid, phosphate, plasma renin activity (PRA), aldosterone and prolactin were evaluated. A significant fall in blood pressure (P less than 0.01) accompanied by an increase in heart rate (P less than 0.01) was attained after 30 min. GFR and RPF increased significantly (P less than 0.01) but the filtration fraction fell. Urine volume and urinary output of sodium, potassium, chloride, calcium, uric acid and phosphate increased markedly (P less than 0.01). Meanwhile, plasma potassium fell (P less than 0.01) and the hormonal parameters showed no significant change. We concluded that in refractory hypertension fenoldopam has potent renal and systemic vasodilatory properties through which blood pressure falls. The hypotensive effect of fenoldopam is also facilitated by its marked diuretic and natriuretic properties. The absence of variations of plasma prolactin confirm the D1 selectivity of fenoldopam and the lack of increase in PRA indicates that fenoldopam blocks the renin-angiotensin aldosterone system. PMID- 2903191 TI - The BBB study: a prospective randomized study of intensified antihypertensive treatment. The BBB study group. AB - The BBB study is a multicentre trial designed to investigate three aspects of antihypertensive treatment of great clinical importance: (1) Is it possible to lower diastolic blood pressure further in treated hypertensive patients (to less than or equal to 80 mmHg) through intensified therapeutic activities? (2) Can this aim be fulfilled without increasing the incidence or severity of side effects to unacceptable levels? (3) If 1 and 2 are answered in the affirmative, will the reduction in diastolic blood pressure give a further reduction in hypertension-associated mortality and morbidity? The BBB study is a prospective trial in which male and female treated hypertensive patients, aged 45-67 years, with treated diastolic blood pressures in the range 90-100 mmHg, will be randomly allocated to either unchanged antihypertensive treatment or intensified treatment with the aim of lowering the diastolic blood pressure to less than or equal to 80 mmHg. Statistical calculations indicate that approximately 2000 patients studied for 3 years will be needed to answer the third question. For this reason the trial will be conducted as a multicentre study performed mainly by primary health care physicians. PMID- 2903192 TI - Limiting dilution analysis of TNF producing cells in C3H/HeJ mice. AB - A limiting dilution assay (LDA) that measures the frequency of TNF producing cells is described. LDA determination is based on the inhibition of growth of a highly TNF sensitive subline from the WEHI-164 fibrosarcoma by using a micro assay sensitive to single picogram amounts of recombinant murine TNF. Using such LDA, it was determined that the reported deficiency in LPS-induced TNF production in C3H/HeJ mice is a function of reduced frequency of TNF producing cells rather than a complete lack of responsiveness. In bulk culture, LPS-triggered TNF was produced by Thy-1.2 negative spleen cells with activity recovered in both G10 Sephadex adherent and nonadherent subpopulations. LPS stimulation of spleen cells from C3H/HeJ mice resulted in TNF mRNA expression as shown in both Northern blots and in situ hybridization. The frequency of TNF mRNA bearing cells in control of C3H/HeSnJ mice by in situ hybridization correlated with that found for TNF producing cells in LDA. In C3H/HeJ spleen, significantly higher numbers of TNF mRNA positive cells were found than were shown to produce TNF in LDA. PMID- 2903193 TI - Functional and biochemical analysis of CD16 antigen on natural killer cells and granulocytes. AB - CD16 Ag is associated with the low affinity FcR for IgG expressed on human NK cells and granulocytes. In this study, we demonstrate that NK cells specifically lyse murine anti-CD16 hybridoma cell lines, but do not lyse hybridomas against other cell surface differentiation Ag expressed on NK cells. Moreover, the CD18 structure is involved in the CD16-specific xenogeneic interaction between human effector cells and murine hybridoma target cells. Although interaction with anti CD16 hybridomas or antibodies triggers the cytolytic mechanism of NK cells, this interaction does not induce cellular proliferation. In contrast to NK cells, CD16+ granulocytes do not lyse anti-CD16 hybridoma cell targets and do not mediate ADCC against antibody-coated human tumor cell targets. These findings indicate a fundamental difference in the antibody-dependent cellular cytotoxicity mechanisms of NK cells and granulocytes. Comparative biochemical analysis of CD16 on NK cells and granulocytes revealed significant differences in the size of the polypeptides obtained after removal of N-linked carbohydrate residues with endo-F and N-glycanase digestion. PMID- 2903194 TI - Analysis of expression of CD2, CD3, and T cell antigen receptor molecules during early human fetal thymic development. AB - To define early stages of T cell maturation during human fetal thymic development, we have used mAb reactive with CD2, CD3, and TCR molecules in indirect immunofluorescence assays on a series of early human fetal thymic specimens. Using a technique of quantitating the relative proportions of fluorescent-positive cells present in tissue sections, we found at 8.5 wk of gestational age after arrival of CD7+ T cell precursors into the thymic rudiment, 60% of thymic CD7+ cells were CD2+, 4% were CD3+ and none was TCR-delta+ or TCR beta+. Moreover, cells reactive with anti-CD2 antibodies against T11(2) and T11(3) epitopes of CD2 as well as thymic stromal cells expressing the CD2 ligand, lymphocyte function associated Ag-3, were also present at 8.5 wk. From 9.5 wk to birth TCR beta+ cells increased to include greater than 90% of all CD7+ cells while TCR-delta+ cells fell from a peak of 11% of CD7+ cells at 9.5 wk to 1% of CD7+ cells at birth. These data suggest that epitopes of CD2 molecules are expressed early on during fetal thymic development. Moreover, these data suggest that CD7+, CD2+, cytoplasmic CD3+ T cell precursors in man give rise to both TCR delta+ T cells as well as to T cells expressing TCR-alpha beta. PMID- 2903195 TI - Role of CD2 in activation and cytotoxic function of CD8/Leu-7-positive T cells. AB - CD3/CD8-positive, Leu-7-positive cells comprise about 3 to 5% of PBL in normal individuals, but the proportion of these cells is increased in patients with a variety of diseases including chronic viral infection, Crohn's disease, and AIDS. To study further the function of these cells, the proliferative and cytotoxic responses of highly purified CD8/Leu-7-positive cells were studied in vitro. These cells had low proliferative responses when exposed to PHA or mitogenic anti CD3 mAb compared to CD8/Leu-7-negative cells, and their proliferative responses were significantly lower after addition of IL-2 or autologous adherent cells. However, the proliferative responses of both Leu-7-positive and Leu-7-negative CD8 cells were similar when stimulated with PHA, Ionomycin, or anti-CD3 in combination with phorbol ester. In addition, CD8/Leu-7-positive cells demonstrated high proliferative responses when exposed to a combination of both PHA and SRBC, and these responses could be inhibited by prior addition of non stimulating anti-CD2.1 mAb. CD8/Leu-7-positive cells, but not CD8/Leu-7-negative cells, mediated lectin- and anti-CD3-induced cytotoxicity against K562 target cells. Cytotoxicity was in part dependent on the CD2 Ag because it was inhibited by anti-CD2.1 mAb. Finally, when small CD8-positive T cells having low cytotoxic potential were activated with PHA plus SRBC, but not PHA alone, there was significant enhancement of their cytotoxic function. Thus, the CD2 receptor may be an important activation pathway for cytotoxic cells. PMID- 2903196 TI - A highly reliable, sensitive, flow cytometric/fluorometric assay for the evaluation of the anti-HIV activity of antiviral compounds in MT-4 cells. AB - Infection of human T4 lymphocyte MT-4 cells with human immunodeficiency virus (HIV) results in cell death 4-5 days after infection. We have now developed a highly sensitive and rapid procedure for estimating the cytopathic effect of HIV in MT-4 cells. This method is based on fluorometric as well as flow cytometric evaluation of HIV-infected MT-4 cultures. By the use of fluorescein diacetate (FDA), a non-fluorescent diacetyl fluorescein ester that becomes fluorescent upon hydrolysis by esterases present in the cytoplasm of viable cells, as few as 100 200 viable MT-4 cells can be accurately determined. Applying this new method to HIV-infected MT-4 cell cultures treated with differing concentrations of the potent anti-HIV agent azidothymidine (AZT), we obtained a virus-inhibitory dose response comparable to those obtained by the conventional (labour-intensive and time-consuming) methods. The FDA-based cell viability assay appears particularly suited for the rapid, reliable and sensitive evaluation of potential anti-AIDS agents in cell culture. PMID- 2903197 TI - Association between restriction fragment length variants of the complement C4 genes and MHC haplotypes. AB - DNA polymorphism of the human major histocompatibility complex (MHC)-linked complement C4 genes was studied using restriction enzymes XbaI and TaqI, and Southern hybridization. The results show that some, but not all, C4 phenotypes can be divided into subtypes. Analysis of MHC haplotypes indicates that in each extended MHC haplotype, i.e. in the haplotypes having a particular combination of HLA and complotype phenotypes in significant linkage disequilibrium, the C4 genes always produce just one 'conserved' restriction enzyme fragment pattern, while in the other haplotypes the C4 genes are more heterogeneous. Furthermore, the findings provide preliminary evidence for a C4B gene duplication, and suggest that the C4 genes may often be 'corrected' alike. PMID- 2903198 TI - The anaerobic and aerobic bacterial flora of leg ulcers in patients with sickle cell disease. AB - Leg ulcers in 26 patients with sickle-cell disease (SCD) were studied bacteriologically over a period of 6 months. The average age of the patients was 20.92 years and the mean duration of the ulcers was 3.43 years. In order of frequency, Staphylococcus aureus, Pseudomonas aeruginosa, and Bacteroides melaninogenicus were the predominant organisms. Anaerobes were isolated from 14 (54%) of 26 patients and represent 21% of the total 77 isolates. The presence of anaerobes correlated well with odorous ulcers. Isolation of anaerobes from leg ulcers of patients with SCD has added to knowledge of bacterial infection in SCD. PMID- 2903199 TI - Amoebic liver abscess in a bisexual man. AB - A bisexual man who had not travelled outside the U.K. had an amoebic liver abscess. Although it is reported that Entamoeba histolytica is usually of a non pathogenic type in homosexual men in the U.K., it is important to diagnose invasive amoebiasis in this high-risk group so that appropriate treatment can be given. PMID- 2903200 TI - Properties of Escherichia coli isolates from urinary tract infections in boys. AB - Fifty-five isolates of Escherichia coli from urine of boys younger than three years of age with urinary tract infection (UTI) were compared with strains from girls of the same age range who had UTI. The frequency of P fimbriae, hemolysin, and type 1C fimbriae, previously described as associated with pyelonephritis (PN) in girls, was also high (76%, 60%, and 31%, respectively) in UTI-associated strains from boys. However, in contrast to isolates from girls, strains from lower UTI in boys did not differ from PN-associated strains regarding these three characteristics. In contrast, aerobactin production was significantly associated with PN compared with lower UTI in both sexes. Serotypes O4 and O6 were overrepresented among all UTI-associated strains from boys and PN-associated strains from girls. This overrepresentation was largely accounted for by three clones, one of which was a new clone identified among the UTI-associated strains from boys. PMID- 2903201 TI - Dihydrolevobunolol is a potent ocular beta-adrenoceptor antagonist. AB - The ocular beta-adrenoceptor antagonist activity of dihydrolevobunolol (DHLB), the major ocular and systemic metabolite of levobunolol was investigated by determining its ability to block isoproterenol-induced ocular hypotension in normotensive rabbits. Topically-applied 0.001% and 0.01% DHLB virtually abolished the response to isoproterenol, indicating a beta-blocking potency similar to that of timolol. Thus, the ocular metabolism of levobunolol leads to the formation of a highly potent beta-adrenoceptor antagonist that may contribute to its clinical efficacy. PMID- 2903202 TI - Celiprolol versus timolol and placebo: a two week double-blind comparison. AB - Celiprolol (5%) was compared to timolol (0.5%) and placebo in patients with primary open angle glaucoma or ocular hypertension. A total of 28 patients participated in this double blind study and received treatment for two weeks. Intraocular pressure decreased an average of 4.4 mmHg with celiprolol and 7.1 mmHg with timolol two hours after instillation. This was maintained 12 hours after administration of timolol but not after celiprolol. There was a small but statistically significant decrease in pulse rate 2 hours after administration of timolol (from 72 to 64 beats per minute) which was not observed after celiprolol. Side effects were mild and similar for all 3 groups. PMID- 2903203 TI - Effects of intraventricular histamine and H2 receptor antagonists on intraocular pressure. AB - Severe ocular hypertension has been reported in a chronic glaucoma patient following use of histamine H2 receptor antagonists for treatment of peptic ulcer. Subsequent studies, however, have failed to demonstrate a significant action of topical or intravenously administered H2 blockers on intraocular pressure (IOP) in humans. In this study, cimetidine and ranitidine were administered into the cerebral ventricles of unanesthetized New Zealand White rabbits. Both drugs caused prolonged increases in IOP at a dose of 1 umol. Maximal elevations of IOP occurred approximately 20 min after drug injections and averaged 5-8 mmHg above pre-drug values. In contrast, histamine (0.3 and 1.0 umol) produced biphasic effects on IOP when given by intracerebroventricular (i.c.v.) injection. These data suggest that central mechanisms may mediate the actions of some histamine receptor agonists and antagonists on IOP. PMID- 2903204 TI - Effects of topically applied falintolol: a new beta-adrenergic antagonist for treatment of glaucoma. AB - Changes in intraocular pressure (IOP) following topical administration of falintolol (0.5%-0.25%), a new beta-blocking agent, were studied in conscious albino rabbits with alpha-chymotrypsin-induced ocular hypertension. The drug produced a reduction in IOP equal to that of timolol. A longer duration of activity was noted with falintolol. The rate of transport of topically applied falintolol through the isolated bovine cornea under conditions simulating normal physiology was linear up to three hours and twice as fast as timolol from 3 to 6 hours. Since topical ocular application of beta-adrenergic antagonists useful in glaucoma therapy can also cause a number of troublesome systemic side effects, several conclusive preclinical investigations were carried out with falintolol. Of major concern was the effect falintolol might have on the pupil, cornea, and heart rate when administered topically. The results show that falintolol does not produce any noteworthy side effects and is capable of being an effective beta blocking agent in open-angle glaucoma therapy. PMID- 2903205 TI - Betaxolol in chronic obstructive pulmonary disease. AB - We evaluated the effect of betaxolol on the pulmonary function tests of nine patients with glaucoma and chronic obstructive pulmonary disease (COPD) requiring beta-blocker therapy. The results of pre-treatment pulmonary function tests were compared to results after two weeks of betaxolol therapy. The mean ratio of forced expiratory volume in one second (FEV-1) to forced vital capacity (FVC) was 59.33 +/- 13.30%. After two weeks of betaxolol therapy, the resulting mean FEV 1/FVC was 57.89 +/- 13.89%, a statistically insignificant difference (P greater than 0.05). The mean FEV-1 was 1.94 +/- 0.83 liters, compared to 1.91 +/- 0.78 liters after two weeks of betaxolol. The mean FVC was 3.19 +/- 0.91 liters, compared to 3.23 +/- 0.89 liters after two weeks of betaxolol. These differences were, also, not statistically significant (P greater than 0.05). This prospective study supports previous reports suggesting that betaxolol has potential advantages for those patients at risk for developing pulmonary side effects from beta-blocker therapy. This report represents the largest single-center series of patients who have been studied in this fashion. PMID- 2903206 TI - Enzymes of mercapturate pathway in cultured bovine ciliary epithelial cells. AB - Relative enzyme activities of the mercapturate pathway were determined in bovine ciliary pigmented (PE) and nonpigmented (NPE) epithelial cells in culture. Glutathione S-transferase activity was greater in PE cells than in NPE cells. Gamma-glutamyl transpeptidase activity appeared to be exclusively associated with NPE cells; the enzyme activity was virtually absent in PE cells. The level of cystine aminopeptidase activity was about the same in NPE and PE cells. N-acetyl transferase was predominantly found in NPE cells. If a similar enzyme distribution should exist in vivo in the bicellular layer of ciliary epithelium, the present result suggests that both NPE and PE cells are involved in the detoxification of xenobiotics via the mercapturate pathway, glutathione conjugation occurring primarily in the PE cells and the reactions catalyzed by the membrane-bound enzymes gamma-glutamyl transpeptidase and N-acetyl transferase taking place mainly in the NPE cells. PMID- 2903207 TI - Effect of the dietary alpha-linolenate/linoleate balance on lipid compositions and learning ability of rats. II. Discrimination process, extinction process, and glycolipid compositions. AB - Donryu strain rats through two generations were fed semi-purified diets supplemented with safflower seed oil (rich in linoleic acid) or with perilla seed oil (rich in alpha-linolenic acid), or a conventional laboratory chow (normal control diet). Brightness-discrimination learning ability was determined to be the highest in the perilla oil-fed group, followed by the normal group, and then by the safflower group, extending our earlier observation in a different strain of rat that alpha-linolenic acid is a factor in maintaining high learning ability (Yamamoto, N., M. Saitoh, A. Moriuchi, M. Nomura, and H. Okuyama. 1987. J. Lipid Res. 28: 144-151). After the brightness-discrimination learning test was administered, extinction of learning was measured. The time required for extinction was significantly longer in the safflower group than in either the perilla group or the normal diet group. Thus, the dietary alpha linolenate/linoleate balance affected both the learning and the extinction of learning. The glycolipids of the cerebrum, cerebellum, and olfactory lobe were analyzed. Although the fatty acid compositions of the sulfatide and gangliosides were significantly different in the three parts of the brain, relatively little difference was observed in the fatty acids of glycolipids between the safflower group and the perilla group, suggesting that gross changes in brain glycolipids are not responsible for the differences in learning abilities between these dietary groups. PMID- 2903208 TI - Purification and characterization of bile salt hydrolase from Clostridium perfringens. AB - Bile salt hydrolase (cholylglycine hydrolase, EC 3.5.1.24) has been purified to homogeneity (792-fold) from Clostridium perfringens using high performance DEAE chromatography. The purified enzyme showed a single detectable protein band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with a relative molecular weight ca. 56,000. The intact enzyme had a relative molecular weight (Mr) of ca. 250,000 as determined by nondenaturing PAGE. The NH2-terminal sequence of bile salt hydrolase was determined to be Met-(Ser/Cys)-Arg-Thr-Lys Leu-Val-Ileu-Thr-Ileu-Gly-Ala-Ser. The purified enzyme was active towards both glycine and taurine conjugates of cholate. The apparent Km and Vmax of the enzyme for glycocholate was estimated to be 0.5 mM and 107 nmol/min.mg protein, respectively. The pH optimum was in the range of 5.8 to 6.4. The enzyme was inhibited 85%, 81%, and 83% by 2 mM iodoacetate, p-chloromercuribenzoate, and phenylmethanesulfonylfluoride, respectively. Rabbit polyclonal antibody was prepared and used to demonstrate a single form of the enzyme in crude cell extracts. PMID- 2903210 TI - In situ hybridization for interleukin 2 and interleukin 2 receptor mRNA in T cells activated in the presence or absence of cyclosporin A. AB - RNA-RNA in situ hybridization was used to study the frequency of cells producing mRNA for IL-2 and IL-2-R in T lymphocytes stimulated by either of three mitogens: anti-CD3, anti-CD28, or PHA. Both CD4+ and CD8+ T cells expressed transcripts for IL-2 and the low-affinity IL-2-R when stimulated with these mitogens plus PMA. IL 2 transcripts peaked at 8-16 h, and IL-2-R at 24-40 h. Cyclosporin A (CSA) inhibited the synthesis of IL-2, but not IL-2-R mRNA, after stimulation by PHA or anti-CD3. However, higher concentrations of CSA were necessary to achieve 50-70% inhibition after stimulation with anti-CD28. At optimal points 12-22% of CD4+ and 5-13% of CD8+ cells expressed IL-2 mRNA, while 30-50% of cells of both subsets had IL-2-R mRNA. The IL-2 grain counts, which relate to the level of mRNA/cell, were higher in the CD4+ subset but could be increased several fold in the CD8+ subset in the presence of adherent accessory cells. The use of PMA as an accessory stimulus, in addition to adherent cells, greatly increased the frequency of lymphocytes with IL-2 mRNA and the amount of IL-2 activity in the culture medium, but the proliferative response was not significantly boosted. These observations indicate at the single cell level that many CD4+ or CD8+ lymphocytes can make IL-2 mRNA, and that the induction of IL-2 with several stimuli is reduced by CSA and enhanced by PMA. PMID- 2903209 TI - Triggering of T cell proliferation through AIM, an activation inducer molecule expressed on activated human lymphocytes. AB - In this report, we describe a novel activation antigen that appears very early after T cell activation and is absent in resting lymphocytes, through which agonistic proliferative signals can be triggered by mAb binding. It has been designated as activation inducer molecule (AIM) and is a disulphide-linked heterodimeric structure containing two polypeptide chains of Mr 33,000 and 27,000. The expression of AIM can be induced by different activation stimuli such as PMA, PHA, or anti-CD3 mAb, but not by the Ca2+ ionophore A23187, and it precedes the expression of other activation molecules such as 4F2 or the IL-2-R. Once AIM antigens are expressed on lymphocytes after stimulation with submitogenic doses of PMA, the binding of anti-AIM mAbs triggers a strong proliferative response. Furthermore, a comitogenic effect of the anti-AIM mAbs is exerted in the presence of either PHA or anti-CD3 mAb. The activation of lymphocytes through AIM antigens induces both IL-2 and IL-2-R receptor synthesis and is inhibited by anti-IL-2-R mAbs. PMID- 2903211 TI - Clonal analysis of functionally distinct human CD4+ T cell subsets. AB - A large number of CD4+ T cell clones, obtained from peripheral blood T lymphocytes by direct limiting dilution, allowed us to address the question whether functional heterogeneity exists within the human CD4+ T cell subset. Cytotoxic capacity of cloned T cells was analyzed with the use of anti-CD3 antibodies and target cells bearing FcR for murine IgG. 6 of 12 CD4+ clones obtained were able to lyse Daudi or P815 cells in the presence of anti-CD3 antibodies. The remaining six CD4+ T cell clones tested did not display anti-CD3 mediated cytotoxic activity and did not acquire this cytotoxic capacity during a culture period of 20 wk. In the absence of anti-CD3 mAb, no lytic activity against Daudi, P815, and K562 target cells was observed under normal culture conditions. Phenotypic analysis of these two distinct types of CD4+ T cells did not reveal differences with regard to reactivity with CDw29 (4B4) and CD45R (2H4) mAbs that have been described to recognize antigens associated with helper suppressor/inducer (respectively) CD4+ cells. The CD4+ clones without anti-CD3 mediated cytotoxic activities (Th2) consistently showed a high expression level of CD28 antigens, whereas the cytotoxic clones (Th1) expressed low amounts of CD28. Th1 CD4+ clones did produce IL-2, IFN-gamma, and TNF-alpha/beta, whereas the Th2 T cell clones produced minimal amounts of IL-2 and only low levels of INF gamma and TNF-alpha/beta in response to anti-CD3 mAbs and PMA. Although not all CD4+ clones did release IL-4, there was no correlation with cytotoxic activity. Moreover, as compared with the Th1 CD4+ clones, Th2 CD4+ T cell clones proliferated moderately in response to immobilized anti-CD3 mAbs. However, proliferation reached the level of the cytotoxic clones when anti-CD28 mABs were present during culture. Both CD4+ subsets provided help for B cell differentiation upon stimulation with anti-CD3 mAbs. Our data suggest that the human CD4+ subset, in analogy to the murine system, comprises two functionally distinct T cell subpopulations, both of which are able to exert helper activity for polyclonal B cell differentiation, but which differ in cytotoxic capacity, lymphokine production, and requirements for proliferation. A function for these two types of T cells in the immune response is discussed. PMID- 2903212 TI - Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. AB - BALB/c mice can be protected against a normally fatal Leishmania major infection by immunization with a partially purified, soluble subfraction of the parasite (fraction 9). In this study, we demonstrate that a T cell line established against fraction 9, designated line 9, transfers protection equivalent to that obtained by active immunization. In contrast, T cell lines (lines 1 and 9.2) responsive to a nonprotective soluble fraction (fraction 1) not only failed to protect BALB/c mice against L. major, but exacerbated the infection. Most importantly, in addition to differing in their antigen specificity, protective and exacerbative T cells lines could be distinguished on the basis of the lymphokines produced, a characteristic previously used to separate murine Th cells into two subsets, designated Th1 and Th2. We found that the protective cell line, line 9, displayed the Th1 property of secreting IL-2 and IFN-gamma, while the exacerbating lines secreted IL-4 and IL-5, a characteristic of Th2 cells. Our results demonstrate that Th1 and Th2 cells may have dramatically different effects on the outcome of an infection, and suggest that susceptibility and resistance in experimental leishmaniasis may depend upon a balance between the Th subsets induced. PMID- 2903213 TI - Molecular characterization of the C3HfB/HeN H-2Kkm2 mutation. Implications for the molecular basis of alloreactivity. AB - The C3HfB/HeN (C3Hf) mouse strain expresses an H-2Kk molecule, previously denoted H-2Kkv1, that is structurally and functionally distinct from H-2Kk of the parental C3H strain. By molecular genetic analysis, we demonstrate that the C3Hf H-2K gene carries a homozygous coding region mutation relative to the C3H allele, revealing that C3Hf meets the requirements for assignment of a mutant haplotype, H-2km2. C3Hf H-2Kkm2 bears a single clustered substitution of four nucleotides within 14 contiguous nucleotides in exon 3. Since this sequence also is present intact at the homologous position in H-2Dk of both C3H and C3Hf, the origin of the H-2Kkm2 mutation is consistent with a nonreciprocal sequence transfer from the H-2Dk donor gene, analogous to the mechanism proposed for generation of the H 2Kb mutations. The H-2Kkm2 mutation encodes three clustered amino acid substitutions, at positions 95, 98, and 99, that map to one of the large beta strands at the bottom of the peptide antigen binding cleft of the H-2Kkm2 molecule. The nature and location of these amino acid substitutions are unique relative to any other known H-2 mutant or HLA variant, and underscore the importance of the beta-pleated sheet in influencing CTL recognition. These results indicate that H-2Kkm2 alloantigenicity may derive largely from altered presentation of self cellular peptides. PMID- 2903215 TI - Rare peripheral T cells migrate to and persist in normal mouse thymus. AB - The traffic of T cells between the thymus and peripheral lymphoid organs is generally thought to be unidirectional. Using a technique of lymphocyte transfer between Thy-1 congenic mice, we demonstrate here the entry of rare peripheral lymph node T cells into the normal mouse thymus. At time points from 3 h to 24 wk after transfer, donor peripheral T cells were present in the host thymus, mainly as scattered single cells confined to the medulla. At 2 wk after transfer, donor T cells constituted 0.2% of the medullary thymocytes (compared with 11% of the peripheral lymph node T cells). As a population, these cells exhibited a stable mature immunophenotype (Ly-1hi, PNAlo, and mixed L3T4- and Lyt-2+). A minority of the donor T cells expressed high levels of the MEL-14 "homing receptor". The thymic medulla thus exhibits features of a peripheral lymphoid organ but differs in its low rate of turnover of recirculating T cells. PMID- 2903214 TI - Murine CD4+ T cell subsets defined. AB - We have used two monoclonal anti-murine T cell autoantibodies (SM3G11 and SM6C10) and multi-color immunofluorescence staining to resolve splenic CD4+ cells into four populations. Two of these populations (Fr. I and Fr. III, 35% and 10% of CD4+ cells) show mutually exclusive expression of these determinants and exhibit distinct functions. Fr. III secretes IL-4, but not IL-2 when activated by Con A, and includes memory T cells responsible for secondary antibody formation. In contrast, Fr. I secretes IL-2 but not IL-4 in response to Con A, and does not contribute to the secondary antibody response. Furthermore, these two fractions exhibit differential accessory cell dependence. Whereas Fr. III responds with B cells (and also non-B cells) as accessory cells in Con A-induced activation, Fr. I requires non-B cells. However, we found that many CD4+ cells (Fr. II, 40% of CD4+ cells) express both determinants and are not distinguishable with regard to lymphokine secretion, accessory cell effect, and memory T cell activity. Curiously, the fraction expressing neither determinant (Fr. IV, 10% of CD4+ cells) is unresponsive to experimental conditions used here. We discuss the possible relationships between these T cell subsets and the implications of differential expression of these determinants. PMID- 2903216 TI - Identification of CD2-/CD3+ T cells in fetal human tissue. AB - From 1 to 23% of fetal human spleen or thymus cells (from the 20th to 24th week of gestation) were found to display a previously unrecognized CD2-/CD3+ phenotype. IL-2-dependent, long-term clones of CD2-/3+ T cells did not react with a panel of anti-CD2 mAbs and did not form rosettes with sheep erythrocytes. These results show that (a) significant numbers of CD2-/3+ T cells are present in fetal human spleen and/or thymus; and (b) in contrast to the widely accepted view, expression of CD2 is not a prerequisite for the expression of the CD3 molecular complex on human T cells. PMID- 2903218 TI - Morphological description of surface structures on strain B41 of bovine enterotoxigenic Escherichia coli bearing both K99 and F41 antigens. AB - In order to describe morphologically the structures on the cell surface of bovine enterotoxigenic Escherichia coli, variants of reference strain B41 (K99+F41+) either negative for K99 and positive for F41 antigens (variants B41A, B41*C), or phenotypically negative for both antigens (variants B41B1, B41B2, B41*CB), and a transconjugant harbouring the K99 plasmid and expressing the K99 adhesin [transconjugant B41 x H510a:H510(2)] were examined by transmission electron microscopy using negative staining. Several negative staining procedures were tested for strain B41 and variant B41A: direct harvesting of strains into ammonium molybdate (2%, w/v), with bacitracin (50 micrograms ml-1) as wetting agent, gave the best results. Three morphologically distinct structures on the cell surface could be identified in cultures grown on Minca medium. Firstly, thin, filamentous, flexible fibrillar structures, presenting a helical structure and a mean diameter of approximately 3 nm, were recognized as K99 fimbriae, since they were present on strain B41 and on transconjugant H510(2), but not on K99 negative variants nor on the recipient strain H510a. Secondly, coil-like structures with a diameter of about 17-20 nm were observed on strain B41 and on variants B41A and B41*C. These structures appeared to consist of two or more curled filaments (diameter 3 nm) joined to coil on themselves into dense spirals. They were very rare in variants B41B1 and B41B2 and were absent on variant B41*CB and on a transconjugant B41* x B41*CB, which had re-acquired the K99 plasmid and which again exhibited K99 fimbriae. Strains B41 and variant B41A gown at 37 degrees C for 24 h on sheep-blood agar exhibited coiled structures like those seen on Minca medium. In contrast, after growth at 18 degrees C for 48 h (which inhibits the synthesis of F41 antigen), coiled structures were no longer expressed on the cell surface of strain B41 and variants B41A and B41*C. Thus the presence of coiled structures correlated with the expression of F41 antigen in strains and variants, which suggests that F41 had a coiled morphology. Finally, straight fimbriae (diameter 6.5-7 nm) were observed on the cell surface of every strain and variant. Their expression on the cell surface was enhanced by several subcultures in th e static broth, and it was inhibited by subculture on agar, but not by culture at 18 degrees C after serial subcultures in static broth. These facts indicated that the straight fimbriae could be common fimbriae, and excluded their being F41 structures. PMID- 2903217 TI - The recombinant 65-kD heat shock protein of Mycobacterium bovis Bacillus Calmette Guerin/M. tuberculosis is a target molecule for CD4+ cytotoxic T lymphocytes that lyse human monocytes. AB - Since little is known about Tc cells in the human immune response to intracellular parasites, we have studied the role of Tc cells in response to M. bovis Bacillus Calmette-Guerin (BCG). Donors whose PBMC responded to BCG, purified protein derivative (PPD), and the recombinant 65-kD heat shock protein (HSP) of BCG generated BCG/PPD-specific CD4+ effector T lymphocytes that lysed PPD as well as recombinant 65-kD-pulsed monocytes. Nonpulsed or irrelevant antigen-pulsed target cells were lysed to a much lower but still significant extent. PPD-stimulated effector lymphocytes of a recombinant 65-kD nonresponder lysed PPD but not recombinant 65-kD-pulsed monocytes. Recombinant 65-kD-educated effector lymphocytes lysed both recombinant 65-kD- and PPD-pulsed monocytes. In addition, these effector cells efficiently lysed nonpulsed target cells. These results demonstrate that in recombinant 65-kD responders, the recombinant 65-kD HSP of BCG is an immunodominant target as well as a triggering molecule for BCG/PPD-specific CD4+ cytotoxic T cells that lyse autologous monocytes. The implications of these findings with respect to the role of the 65-kD HSP in autoimmunity are discussed. PMID- 2903219 TI - Differential performance of acute and chronic schizophrenics in a latent inhibition task. AB - Differences between acute (N = 26) and chronic (N = 27) schizophrenics diagnosed by Research Diagnostic Criteria and normal controls (N = 53) were examined in a task measuring latent inhibition, i.e., the retardation of learning that normally occurs when a subject forms an association to a stimulus previously repeatedly presented without consequence. In rats, latent inhibition is disrupted by amphetamine and restored by neuroleptics. It was predicted that latent inhibition would be similarly disrupted in acute schizophrenics (presumably in a hyperdopaminergic state) but not in chronic, medicated schizophrenics. Each group was subdivided and assigned randomly to two experimental conditions, preexposure or non-preexposure. Preexposed subjects first heard 30 bursts of white noise through headphones while monitoring a list of nonsense syllables; non-preexposed subjects listened to the nonsense syllables without the white noise. Subjects in both conditions were then given the opportunity to learn that the noise signalled increments in a visually displayed number. Preexposed normals and chronic schizophrenics learned this association more slowly than non-preexposed subjects (latent inhibition); as predicted, acute schizophrenics failed to display this effect. After 6 to 7 weeks, 11 acute and 13 chronic patients were retested; both groups now showed latent inhibition. These results are discussed in relation to the dopamine hypothesis of schizophrenia. PMID- 2903220 TI - Increased extrapyramidal symptoms with addition of lithium to neuroleptics. AB - To explore whether lithium exacerbates neuroleptic-induced extrapyramidal symptoms (EPS), the authors prospectively rated 10 patients on neuroleptics before and after the addition of lithium. EPS ratings increased steadily after the initiation of lithium and were significantly elevated compared with baseline. Individual items that increased significantly were: gait, shoulder shaking, elbow rigidity, and tremor. These findings indicate that usual therapeutic levels of lithium may significantly worsen neuroleptic-induced EPS. Potential mechanisms for this interaction are discussed. PMID- 2903221 TI - Uptake of amino acids by brain microvessels isolated from rats with experimental chronic renal failure. AB - The neurological disorders seen in patients with chronic renal failure and liver cirrhosis are analogous. Previous in vivo studies have shown that the impaired blood-brain amino acid transport seen in rats with chronic renal failure is similar to that of rats with portocaval anastomosis. To elucidate whether a comparable underlying pathogenic mechanism plays a role in both pathological conditions, blood and brain amino acid levels together with amino acid transport by isolated brain microvessels have been studied in rats with chronic renal failure and in sham-operated rats. Brain microvessels isolated from rats with experimental chronic renal failure showed that the uptake of labeled large neutral amino acid, i.e., leucine or phenylalanine, but not of lysine or alpha methylaminoisobutyric acid, was significantly increased with respect to sham operated rats; conversely, the uptake of glutamic acid in rats with chronic renal failure was significantly lower compared with values in controls. Kinetic analysis indicated that this was mainly due to increased exchange transport activity (Vmax) of the L-system, rather than to changes in the affinity (Km) of the carrier system for the relative substrate. These data, together with the significant rise of brain glutamine levels and an increased brain-to-plasma ratio of the sum of large neutral amino acids, are analogous to what was previously observed in rats with portocaval anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903222 TI - Effects of neurotransmitters on astrocyte glycogen stores in vitro. AB - We have used receptor binding assays to determine the presence of three neurotransmitter receptors in a crude membrane fraction derived from neonatal rat cortical astrocyte cultures and subsequently determined the effects of transmitter receptor activation on astrocyte glycogen content in vitro. beta Adrenergic (KD = 88 pM; Bmax = 51 fmol/mg of protein), serotonin (KD = 70 nM; Bmax = 44 pmol/mg of protein), and muscarinic cholinergic receptors (KD = 79 pM; Bmax = 44 fmol/mg of protein) were found to be present on astrocyte membranes using [3H]dihydroalprenolol, [3H]serotonin, and [3H]quinuclidinyl benzilate, respectively, as ligands. Astrocyte cultures exposed to noradrenaline but not specific alpha- and beta-receptor agonists contained 33% less glycogen than controls. Neither serotonin nor carbachol caused alterations in astrocyte glycogen content under normal conditions. Reserpine-treated cultures, however, responded to serotonin with a 28% decrease in glycogen content and contained higher levels of glycogen than non-reserpine-treated controls (a 55% increase). These results show that both noradrenaline and serotonin can evoke astrocyte glycogenolysis and that noradrenergic control of glycogen metabolism is probably exerted through both alpha- and beta-receptors. Neurotransmitter control of astrocyte glycogen turnover may represent a form of neuron-astrocyte signalling in addition to that provided by changes in external potassium concentration. PMID- 2903223 TI - Foot-shock stress and anxiogenic beta-carbolines increase t [35S]butylbicyclophosphorothionate binding in the rat cerebral cortex, an effect opposite to anxiolytics and gamma-aminobutyric acid mimetics. AB - The effect of foot-shock stress on t-[35S]butylbicyclophosphorothionate [( 35S]TBPS) binding to fresh unwashed membrane preparations from rat cerebral cortex was studied and was compared to those of GABAA receptor agonists and antagonists and to positive and negative modulators of the GABAergic transmission. [35S]TBPS binding was increased in the cerebral cortex of rats exposed to foot shock compared to that of nonstressed rats. Scatchard analysis revealed that the effect of foot shock was due to an increase in the total number of [35S]TBPS binding sites. In contrast, the in vitro addition of muscimol or GABA induced a dose-dependent inhibition of [35S]TBPS binding, an effect abolished by the concomitant addition of the GABA receptor antagonist, bicuculline, which, per se, enhanced [35S]TBPS binding by 73%. Thus, bicuculline, similar to stress, increased [35S]TBPS binding in the same membrane preparation. In contrast to stress, the anxiolytic and positive modulators of the GABAergic transmission (ZK 93423, ZK 91296, and diazepam) inhibited the specific binding of [35S]TBPS in a concentration-dependent manner. The greatest inhibitory effect was produced by ZK 93423 at 30 microM (31% of control), followed by diazepam (54% of control) and by the partial agonist ZK 91296 (61% of control). Scatchard plot analysis indicated that the inhibition induced by ZK 93423 and diazepam was due to a decrease in the density of [35S]TBPS recognition sites. On the other hand, the anxiogenic beta-carbolines DMCM and FG 7142 mimicked the effect of stress. Thus, at a 10 microM concentration, DMCM and FG 7142 increased [35S]TBPS binding by 22% and 26%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903224 TI - Differentiation of human neuroblastoma cells: marked potentiation of prostaglandin E-stimulated accumulation of cyclic AMP by retinoic acid. AB - Neuroblastoma cells in culture contain low levels of cyclic AMP, a second messenger which plays a major role in neuronal maturation. In this study, human neuroblastoma cells, SK-N-SH-SY5Y, were induced to differentiate by treatment with either nerve growth factor (50 ng/ml), retinoic acid (10 microM), dibutyryl cyclic AMP (1 mM), or 12-O-tetradecanoylphorbol-13-acetate (0.1 microM), and the ability of several neurotransmitters or hormones to stimulate adenylyl cyclase was tested. Although all four differentiation factors caused morphological changes towards a neuronal phenotype, only retinoic acid dramatically enhanced cyclic AMP accumulation, specifically upon stimulation with prostaglandin E1 (PGE1). PGE2 was also active, but less potent, than PGE1, whereas the other cyclic AMP-stimulating agents tested were largely unaffected. Further, the rapid desensitization of the PGE1-cyclic AMP response observed in control cells after 20 min of PGE1 exposure did not occur in retinoic acid-treated cells, and the EC50 values for PGE1 were reduced from approximately 240 to 14 nM after retinoic acid treatment. The increased sensitivity to PGE was associated with an increase of high-affinity PGE1 binding sites, whereas the Gs coupling proteins and adenylyl cyclase were not measurably affected. A similar enhancement of the PGE1 cyclic AMP response by retinoic acid was also observed in two additional human neuroblastoma cell lines tested, Kelly and IMR-32, suggesting that up-regulation of the prostaglandin response by retinoic acid is common among neuroblastoma cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903225 TI - Excitatory amino acid release from rat hippocampal slices as a consequence of free-radical formation. AB - The release of D-[3H]aspartate, [3H]noradrenaline, and of endogenous glutamate and aspartate from rat hippocampal slices was significantly increased when the slices were incubated with xanthine oxidase plus xanthine to produce superoxide and hydroxyl free radicals locally. Allopurinol, a specific xanthine oxidase inhibitor, the hydroxyl-radical scavenger D-mannitol, or the superoxide-radical scavenger system formed by superoxide dismutase plus catalase prevented this release. These results suggest that endogenous excitatory amino acids are released consequent to the formation of free radicals. The excess of glutamate and aspartate released by this mechanism could be one of the factors contributing to the death of neurons after anoxic or ischemic injuries. PMID- 2903226 TI - The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes. AB - The present study attempted to identify an alpha-2 agonist that could improve working memory in aged nonhuman primates without the marked hypotensive and sedative side effects produced by clonidine. Toward this end, the hypotensive, sedative, and memory-altering properties of the alpha-2 adrenergic agonists, B HT920 and guanfacine, were compared with clonidine's effects in 9 aged rhesus monkeys. Memory capacity was assessed by a variable delay, spatial delayed response paradigm that requires the animal to remember information over short temporal intervals and to update this information on every trial. B-HT920 was found to produce a dose-response profile qualitatively similar to, but weaker than, clonidine: low doses impaired memory and began to lower blood pressure and produce sedation, while high doses improved memory. In contrast, guanfacine produced a dose-response profile opposite to that seen with clonidine: low doses improved memory without inducing hypotension or sedation, while the memory impairing, hypotensive, and sedating properties of the drug were observed at higher doses. The potency of the 3 agonists to lower blood pressure was clonidine = B-HT920 greater than guanfacine; sedation was affected in the order clonidine greater than B-HT920 greater than guanfacine; for memory impairment, as measured by performance on the delayed response task, the rank order potency was clonidine greater than B-HT920 greater than guanfacine, while for memory improvement it was guanfacine greater than clonidine greater than B-HT920. These differences in rank order potency are consistent with the recent proposal of alpha-2 receptor subtypes, a rauwolscine-sensitive site (Rs) that binds clonidine greater than B HT920 greater than guanfacine and a rauwolscine-insensitive site (Ri) that binds guanfacine greater than clonidine greater than B-HT920 (Boyajian and Leslie, 1987). The data suggest that the hypotensive, sedating, and memory-impairing effects of alpha-2 agonists may be due to actions at one subtype of receptor (Rs), while the memory-enhancing effects of these drugs may result from actions at another alpha-2 receptor subtype, the Ri site. The ability of low doses of guanfacine to improve memory without inducing hypotension or sedation indicates that this agonist may be an excellent candidate for treating memory disorders in man. PMID- 2903227 TI - Inward rectification of resting and opiate-activated potassium currents in rat locus coeruleus neurons. AB - Intracellular recordings were made from rat locus coeruleus neurons in vitro, and membrane currents were measured at potentials from -50 to -130 mV. In the absence of any applied agonists, the slope conductance of the cells increased 3-fold when the cell was hyperpolarized from -60 to -120 mV. This conductance increase was complete within 5 msec of the onset of a hyperpolarizing command and was subsequently independent of time for several seconds. The conductance increase was blocked by cesium chloride (1-2 mM), rubidium chloride (1-2 mM), or barium chloride (1-100 microM). The membrane potential range over which the conductance increased was centered at the potassium equilibrium potential (EK; extracellular potassium concentration, 2.5-10.5 mM): the current/voltage (I/V) relation of the cell could be well described by supposing that there were 2 potassium conductances, one voltage independent (G1) and the other (inward rectifier, Gir) activated according to the expression Gir = Gir,max/(1 + exp[(V - EK)/k]), where k ranged from 15 mV in 2.5 mM potassium to 6 mV in 10.5 mM potassium. The additional membrane potassium conductance that developed when agonists at mu opioid and alpha 2-adrenoceptors were applied also became larger with membrane hyperpolarization, and this voltage dependence was also reduced or blocked by rubidium, cesium, and barium; in the presence of these agonists the current also reached its final value within 5 msec. However, the conductance increased by the agonists (Gag) was not well expressed by simply increasing the values of G1 and Gir,max. It was best described by a potassium conductance that increased according to Gag,max/(1 + exp[(V - Vm)/k]), where Vm (the potential at which the conductance was half-maximum) was close to the resting potential of the cell.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2903228 TI - Interaction of vitamin E and its model compounds with unsaturated fatty acids in homogeneous solution. AB - Either alpha-tocopherol (vitamin E) or one of its model compounds having side chains of different length at the 2-position of alpha-tocopherol, forms complexes with an unsaturated fatty acid in methanol. For complex formation, the isoprenoid side chain and hydroxy group of alpha-tocopherol are unessential and, rather, the methyl groups attached to the aromatic ring of the chromanol moiety seems to be responsible. For better interaction, more than three methylene-interrupted Z double bonds of a fatty acid are necessary. These findings are incompatible with the hypothesis of Diplock and Lucy on the interaction of vitamin E with each polyunsaturated fatty acid. PMID- 2903229 TI - Ribotype analysis of Pseudomonas cepacia from cystic fibrosis treatment centers. PMID- 2903230 TI - Hepatic injury during rotavirus infections. PMID- 2903231 TI - Plasma levels of somatostatin and gastrin in sick infants and small for gestational age infants. AB - Sick neonates often have a disturbed gastrointestinal motility. As somatostatin inhibits various gastrointestinal functions, we investigated whether or not somatostatin levels are high in sick infants. Somatostatin and gastrin levels were measured in plasma samples collected from sick and healthy neonates. Somatostatin levels were found to be significantly elevated in sick infants when compared to healthy ones, both term (91 versus 5 pM) and preterm (35 versus 5 pM). We suggest that the gastrointestinal symptoms seen in infants during illness may be related to an enhanced secretion of gastric somatostatin. PMID- 2903232 TI - Isolation and characterization of an amphiphilic form of human intestinal aminopeptidase N. AB - An amphiphilic detergent-solubilized human adult intestinal microvillous aminopeptidase N (EC 3.4.11.2) was purified by immunoadsorbent technique using meconial aminopeptidase N antibodies. Its molecular and kinetic properties were investigated to confirm the differences previously observed from the meconial enzyme. PMID- 2903233 TI - Selective alpha-2 adrenoceptor agonists alter fluid and electrolyte transport in mammalian small intestine. AB - The effects of the selective alpha-2 adrenoceptor agonists B-HT 920 and B-HT 933 on fluid and electrolyte transport in mammalian small intestine were assessed in vitro and in vivo. In Ussing flux chamber preparations of rabbit ileum, B-HT 920 reduces basal short-circuit current (Isc) in a concentration-dependent manner. This in vitro effect is inhibited by rauwolscine (KB = 9.7 nM) but not by prazosin. Isotope flux and ion replacement studies suggest that this decrease in Isc is due primarily to stimulation of a HCO3-dependent transport process. B-HT 920 promptly attenuates the 16,16-dimethyl prostaglandin E2 (dmPGE2)-stimulated increase in Isc and completely reverses dmPGE2-stimulated Cl secretion to absorption. Oral administration of B-HT 933 dose-dependently inhibits dmPGE2 induced enteropooling in conscious rats. This effect of B-HT 933 is likewise blocked significantly by rauwolscine but not by prazosin. Similar effects of B-HT 933 are observed on enteropooling in the pithed rat as are the effects of B-HT 920 in the conscious rat. These results indicate that selective alpha-2 adrenoceptor agonists from the azepine class of compounds have significant proabsorptive and antisecretory activities in the rabbit small intestine in vitro and in the rat intestine in vivo. This in vivo effect does not appear to be central nervous system mediated. These studies suggest that these alpha-2 adrenoceptor agonists may be useful in converting the hypersecreting mammalian small bowel to its normal absorptive state. PMID- 2903234 TI - Stimulant and hallucinogenic behavioral profiles of 3,4 methylenedioxymethamphetamine and N-ethyl-3,4-methylenedioxyamphetamine in rats. AB - The effects of methylenedioxymethamphetamine (0.63-10.0 mg/kg) and N-ethyl methylenedioxyamphetamine (1.0-10.0 mg/kg) on locomotor and investigatory responses of rats were measured in the Behavioral Pattern Monitor system, a system designed to measure both the quantity and quality of behavioral activity. Horizontal locomotion was increased considerably by these compounds in a dose related manner. This hyperactivity was accompanied by an initial decrease in investigatory holepokes and rearings followed by a subsequent increase at the highest doses tested. Rats injected with these phenylethylamine derivatives also exhibited thigmotaxis and a tendency to avoid the center of the experimental chamber, a behavioral profile similar to hallucinogen-like drugs. Consequently, a disruption of the spatial patterns of locomotion was also observed. Analyses of these patterns revealed an increasing tendency toward more stereotyped, predictable locomotor paths with increasing dose. Rats circled around the perimeter of the chamber with individual animals demonstrating a predominant though not completely consistent direction of rotation. The methylenedioxymethamphetamine-induced increase in locomotion remained significantly elevated up to 4 hr after injection at a 10 mg/kg dose, whereas other aspects of motor activity returned to base-line levels more rapidly. Thus, methylenedioxymethamphetamine and N-ethyl-methylenedioxyamphetamine seem to possess both psychomotor stimulant properties and elements of a hallucinogen-like behavioral profile. PMID- 2903235 TI - Endothelium-dependent effects of carteolol. AB - Experiments were designed to study the effect of the beta adrenergic antagonist, carteolol, on the endothelium-dependent responsiveness of isolated arteries. Rings of canine coronary arteries were suspended in organ chambers for isometric tension recording; carteolol inhibited the relaxation to isoproterenol and abolished the difference in responsiveness to the beta adrenergic agonist between rings with and without endothelium. Carteolol did not cause endothelium-dependent relaxations of femoral or coronary arteries. In bioassay experiments, carteolol augmented the basal release of relaxing factors from the endothelium of the femoral artery; this effect was prevented by indomethacin. In rings of femoral arteries, carteolol increased the endothelium-dependent relaxations induced by the alpha-2 adrenergic agonist UK 14,304; this was not affected by indomethacin but prevented by propranolol. Carteolol did not modify the endothelium-dependent relaxations to acetylcholine, adenosine diphosphate, bradykinin, thrombin and the Ca+-ionophore A23187. Carteolol inhibited the endothelium-dependent hypoxic contraction of the canine coronary artery. It did not affect endothelium dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat. These experiments suggest that carteolol facilitates the abluminal release of endothelium-dependent relaxing factor caused by alpha-2 adrenergic activation, and causes the intraluminal release of vasodilator prostaglandins. The compound prevents the endothelium-dependent contractions which are not mediated by products of cyclooxygenase. These actions may contribute to the vasodilatator properties of carteolol in the intact organism. PMID- 2903236 TI - Pharmacologic characterization of SK&F 104078, a novel alpha-2 adrenoceptor antagonist which discriminates between pre- and postjunctional alpha-2 adrenoceptors. AB - SK&F 104078 has been reported to be a moderately potent antagonist at postjunctional alpha-2 adrenoceptors in canine saphenous vein, rabbit saphenous vein and canine saphenous artery (KB = 76-150 nM). In contrast, SK&F 104078 has been found to have essentially no affinity for prejunctional alpha-2 adrenoceptors in the guinea pig atrium. To characterize further the pharmacology of SK&F 104078 we have examined its effects in several additional alpha-2 adrenoceptor models and on several non alpha adrenoceptor-mediated vascular responses. SK&F 104078 does not block the neuroinhibitory effect of alpha methylnorepinephrine in the guinea pig ileum. In contrast, in the rat vas deferens, high concentrations of SK&F 104078 (3-30 microM) antagonized the neuroinhibitory effect of UK 14,304; however, the antagonism was not competitive. At concentrations up to 1 microM, SK&F 104078 did not potentiate [3H]overflow from guinea pig vas deferens or guinea pig atrium prelabeled with [3H]norepinephrine, indicating no prejunctional alpha-2 adrenoceptor blocking activity in these tissues. SK&F 104078 is a competitive antagonist at alpha-1 adrenoceptors, and at 5-hydroxytryptamine2 receptors, as demonstrated by blockade of norepinephrine- and serotonin-induced contraction in the rabbit aorta, with KB values of 155 and 20 nM, respectively. At concentrations up to 10 microM, SK&F 104078 does not depress angiotensin II-induced contraction of rabbit aorta. At 1 microM, no depression of the response to Ca++ in depolarized rabbit aorta is observed, although a significant inhibition of this response is seen at 10 microM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903237 TI - Release-regulating D-2 dopamine receptors are located on striatal glutamatergic nerve terminals. AB - The effects of dopamine (DA) and other dopaminergic receptor agonists on the depolarization-evoked release of endogenous glutamic acid (GLU) have been studied using synaptosomes prepared from rat corpus striatum and depolarized in superfusion with 15 mM KCl. DA and the selective D-2 receptor agonists quinpirole (LY-171555, the levorotatory enantiomer of LY-141865) and pergolide inhibited GLU release in a concentration-dependent way. The natural agonist was particularly effective causing 50% inhibition of GLU release at 10 nM. In contrast, the selective D-1 receptor agonist SK&F 38393 did not affect the release of GLU. The inhibitory effect of DA on the K+-evoked release of GLU was antagonized in a concentration-dependent manner by the selective D-2 receptor antagonist S sulpiride, but not by the R-enantiomer. The data represent a direct demonstration that receptors sensitive to nanomolar concentrations of DA and belonging to the D 2 type are located on GLU axon terminals in the rat corpus striatum where they may modulate the release of GLU from glutamatergic afferents including the cortico-striatal pathway. PMID- 2903238 TI - Mechanism of histamine-induced epinephrine release in guinea pig. AB - The aims of this study were to provide direct evidence that in anesthetized guinea pigs i.v. administration of histamine induces sympathoadrenal activation and to identify the source and mechanism of histamine-induced epinephrine release. Plasma epinephrine measurements were used as the index of sympathoadrenal activity. In intact guinea pigs, histamine infusion caused a 3 fold rise in plasma epinephrine levels. In guinea pigs pretreated with 6 hydroxydopamine to obtain chemical sympathectomy, the rise in plasma epinephrine induced by histamine was distinctly smaller than in controls. This rise was completely inhibited in guinea pigs pretreated with the ganglion blocking agent hexamethonium and in pithed guinea pigs. Pretreatment with the H2-receptor antagonist cimetidine or the H1-receptor antagonist mepyramine reduced the rise in plasma epinephrine. These results demonstrate that in guinea pigs, epinephrine is released not only from the adrenal medulla but also from nerve endings and that histamine releases epinephrine by indirect action through central reflex pathways. PMID- 2903239 TI - Transmitter-induced glycogenolysis and gluconeogenesis in leech segmental ganglia. AB - 1. The utilization and control of glycogen stores were studied in the isolated segmental ganglia of the horse leech, Haemopis sanguisuga. The glycogen in the ganglia was extracted and assayed fluorimetrically and its cellular localization and turnover studied by autoradiography in conjunction with [3H] glucose. 2. The glycogen levels were measured after incubation with different neurotransmitters for 60 min at 28 degrees C. The results for each experimental ganglion were compared to a paired control ganglion, and the results analysed by paired t tests. 3. Several transmitter substances (5-HT, octopamine, dopamine, noradrenaline, histamine) produced reductions in glycogen (glycogenolysis); other transmitters (glutamate, GABA) produced increases in glycogen (gluconeogenesis); others (adenosine, glycine) produced reductions or increases, depending on concentration. Acetylcholine had no effect on the glycogen levels. 4. Most of the glycogen in the ganglia is localized in the packet glial cells, which surround the neuron perikarya. Autoradiographic analysis demonstrated that the effects of histamine and dopamine were principally on the glycogen in the glial cells. 5. Adenylate cyclase was demonstrated by electron microscope histochemistry to be localized on the plasma membranes of the glial cells, and to a lesser extent on the neuronal membranes. 6. It is concluded that the changes in glycogen in the glial cells may be party controlled by transmitters via adenylate cyclase. This may provide a sensitive mechanism for coupling neuronal activity with energy metabolism. PMID- 2903240 TI - Changes of enzymes involved in DNA synthesis in the testes of cryptorchid rats. AB - The activities of DNA polymerase alpha (EC 2.7.7.7) and topoisomerase I did not fluctuate up to 7 days after surgery to induce cryptorchidism and showed no significant difference from those in control testes (sham-operated). In contrast, the activity of DNA polymerase beta decreased by 43% at 5 days (P less than 0.01) and by 47% at 7 days (P less than 0.001). The activity of DNA polymerase gamma also decreased by 46% at 3 days (P less than 0.02) and by 78% at 7 days (P less than 0.01) after surgery. The amount of mRNA for DNA polymerase beta decreased in parallel with enzyme activity. Since the sensitivity to heat inactivation of testicular DNA polymerase beta was exactly the same as that from liver, the decrease in DNA polymerase beta activity may be, at least in part, due to reduced biosynthesis of enzyme protein. The morphological changes in cryptorchid testes suggested that the decrease in DNA polymerase beta and gamma activities might be related to the deleterious effects of elevated temperature on spermatogenesis. PMID- 2903241 TI - Behcet's colitis with oesophageal ulceration treated with sulphasalazine and cyclosporin. PMID- 2903242 TI - Reversible pulmonary disease and eosinophilia associated with sulphasalazine. PMID- 2903243 TI - Modeling of beta-adrenoceptors based on molecular electrostatic potential studies of agonists and antagonists. AB - The molecular electrostatic potential (MEP) of 32 beta-adrenoceptor ligands, mainly antagonists, was calculated by the STO-3G ab initio quantum mechanical method. The MEP of phenylethanolamines (PEAs) features a negative minimum in the meta region (designated M1) which is topographically equivalent to a minimum (designated M2) found in the vicinity of the aromatic ring in all (aryloxy)propanolamines (AOPAs). In these compounds, a second negative zone located beyond the meta position and designated M3 is found in all beta 1 selective antagonists and in some nonselective and beta 2-selective antagonists. The beta 1-selective antagonists feature in the para position an additional zone which is positive (P4) in the full antagonists and negative (M4) in the antagonists displaying intrinsic sympathomimetic activity (ISA). The MEP-based pharmacophoric models of PEAs, AOPAs, and oxime ethers show common elements and lead to a proposed general model for beta-adrenoceptor ligands. PMID- 2903244 TI - Antiallergy agents. 1. Substituted 1,8-naphthyridin-2(1H)-ones as inhibitors of SRS-A release. AB - A novel class of antiallergy agents, the substituted 1,8-naphthyridin-2(1H)-ones, is described. The present compounds are orally active, potent inhibitors of allergic and nonallergic bronchospasm in animal models. Structure-activity studies of the lead compound in this series, 1-phenyl-3-n-butyl-4 hydroxynaphthyridin-2(1H)-one (11), identified three compounds of interest, 1 phenyl-3-(2-propenyl)-4-acetoxy-1,8-naphthyridin-2(1H)-one (12), 1-(3' chlorophenyl)-3-(2-propenyl)-4-acetoxy-1,8-naphthyridin-2(1H )-one (87), and 1 (3'-methoxyphenyl)-3-(2-propenyl)-4-acetoxy-1,8-naphthyridin-2(1 H)-one (89). The mechanism of antiallergy activity may involve inhibition of the release of the sulfidopeptide leukotrienes. 1-Phenyl-3-(2-propenyl)-4-acetoxy-1,8-naphthyridin 2(1H)-one, Sch 33303 (12), was selected for preclinical development as an antiallergy agent. PMID- 2903245 TI - Synthesis and beta-adrenergic antagonism of 2-(aryloxy)-1-(2-piperidyl)ethanols. AB - A series of erythro- and threo-2-(aryloxy)-1-(2-piperidyl)ethanol derivatives (3) was synthesized from 2-(2-oxiranyl)pyridine for evaluation as beta-antagonists. Most compounds displayed high competitive beta-blocking potency, but they lacked significant beta 1/beta 2 selectivity. The 1-naphthoxy derivative erythro-3b was 17 (beta 1) and 33 (beta 2) times more potent than its open-chain analogue, propranolol. Within the whole series, erythro-3 diastereomers were more potent beta-blockers than the threo-3 isomers, and the potency of the latter seems to be rather insensitive to structural modification. The effect of N-methylation and of interposition of an alkyl chain between the aromatic ring and the side chain, while being detrimental to beta-blocking activity, was less marked than in the classic (aryloxy)propanolamine blockers. PMID- 2903246 TI - Design and synthesis of somatostatin analogues with topographical properties that lead to highly potent and specific mu opioid receptor antagonists with greatly reduced binding at somatostatin receptors. AB - A series of conformationally restricted, cyclic octapeptides containing a conformationally stable tetrapeptide sequence related to somatostatin, -Tyr-D-Trp Lys-Thr-, as a template, were designed and synthesized with the goal of developing highly potent and selective mu opioid antagonists with minimal or no somatostatin-like activity. Three distinct structures of the peptide became targets of chemical modifications and constraints; the N- and C-terminal amino acids and the cyclic 20-membered ring moiety. Based on the conformational analysis of active and inactive analogues of the parent peptide D-Phe1-Cys2-Tyr3 D-Trp4-Lys5-Thr6-Pen7+ ++-Thr8-NH2, CTP (Kazmierski, W.; Hruby, V. J. Tetrahedron 1988, 44, 697-710), we designed analogues to include the tetrahydroisoquinolinecarboxylate (Tic) moiety as the N-terminal amino acid instead of D-Phe, since Tic can exist only as a gauche (-) or a gauche (+) conformer. In this series, the following peptides were synthesized and pharmacologically evaluated: D-Tic-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (TCTP), D Tic-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (TCTOP), and D-Tic-Cys-Tyr-D-Trp-Arg-Thr Pen-Thr-NH2 (TCTAP). In rat brain membrane opioid radioligand binding assays, all three peptides displayed high affinity for mu opioid receptors (IC50 = 1.2, 1.4, 1.2 nM, respectively), and exceptional mu vs delta opioid receptor selectivity: 7770, 11,396, and 1060, respectively. TCTOP and TCTAP also possess exceptional mu vs somatostatin receptor selectivity: 14,574 and 28,613, respectively. In the peripheral in vitro GPI bioassay, TCTP, TCTOP, and TCTAP were highly effective antagonists of the potent mu opioid receptor agonist PL017, with pA2 = 8.69 for TCTAP, 8.10 for TCTP, and 7.38 for TCTOP. Our results show that a 10-fold higher affinity and selectivity for mu opioid receptors (in both central and peripheral studies) over delta and somatostatin receptor was gained as a result of the D Tic1 substitution. These three peptides, TCTP, TCTOP, and TCTAP, are the most potent and selective mu opioid antagonists known. CTP has been shown to possess prolonged biological action, much longer than that of naloxone. This renders these analogues potentially useful ligands for investigating the physiological functions of the mu opioid receptor. Analogues of TCTP in which the 20-membered disulfide ring was contracted by deletion of D-Trp4, and/or Lys5, and/or Thr6 led to compounds with greatly reduced potency at the mu opioid receptor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2903247 TI - Synthesis and pharmacology of trans-4-n-propyl-3,4,4a,10b-tetrahydro-2H,5H-1 benzopyrano[4,3-b ]-1,4-oxazin-7- and -9-ols: the significance of nitrogen pKa values for central dopamine receptor activation. AB - The 6-oxa analogues of potent dopamine agonists, hexahydronaphthoxazines (4a,4b), have been tested for dopamine receptor binding and stimulating activity and were found to be almost inactive. pKa value determinations indicated that these compounds are protonated to approximately 2%, while potent compounds are protonated to a much greater extent. These results strongly support the assumption that the protonated form of DA agonists is the active species at the receptor. PMID- 2903249 TI - Restriction enzyme analysis of the mitochondrial genome in mitochondrial myopathy. AB - The mitochondrial myopathies are a heterogeneous group of disorders some of which may be caused by mutations in the mitochondrial genome. Mitochondrial DNA from 10 patients with mitochondrial myopathy and their mothers was analysed using five restriction enzymes and 11 mitochondrial probes in bacteriophage M13. No abnormalities were found in seven out of the 10 patients. Polymorphisms which have not previously been reported were detected in three patients and two of their mothers. These results exclude the presence of deletions or insertions of greater than 60 bp in the region of the mitochondrial genome examined. Any causative mitochondrial DNA mutations in these disorders are therefore likely to be point mutations or small structural rearrangements. PMID- 2903248 TI - Considerations in using linkage analysis as a presymptomatic test for Huntington's disease. AB - The polymorphic locus D4S10 that is genetically linked to the locus for Huntington's disease (HD) has made possible a presymptomatic test for those at risk. Because the symptoms of this progressively debilitating and fatal illness are not usually manifest until adulthood, the outcome of the test will influence major decisions about career, marriage, and procreation. Several differential diagnoses must be considered before using the test if HD is not confirmed in at least one family member. Review of a large number of pedigrees has shown that 40% of persons at risk do not have appropriate family structure for a linkage test. Furthermore, uncooperative or inaccessible relatives may make this test infeasible for many others who wish to be tested. Linkage phase, which must be known in the affected parent for an informative test, can be determined using one or more of 12 probe-enzyme combinations for D4S10. Although the polymorphism information content (PIC) value for any one RFLP is less than 40%, the PIC value for the haplotype of the two G8 HindIII, pK083 EcoRI, and R7 BglII RFLPs is greater than 88%. We have developed a scheme to incorporate linkage data and age at onset information adjusted for censored observations, sex of affected parent, and familial correlation for age at onset, using the computer program MLINK for calculation of risk of having HD. Simulated experiments showed that proper age at onset adjustment is crucial to the calculation of the probability of risk. A formal presymptomatic testing protocol, including pre- and post-test counselling, psychological testing, and paternity testing is recommended. Many of these considerations are illustrated in several actual test cases. PMID- 2903251 TI - Naturally crystalline porin in the outer membrane of Bordetella pertussis. AB - The Gram-negative bacterium Bordetella pertussis is the agent responsible for whooping-cough, and much interest has focused on the functions, structures and immunological properties of the molecules exposed at its outer surface. We have found by electron microscopy that cells of two strains of B. pertussis are covered with a crystalline surface lattice. This lattice is not an extrinsic layer of high molecular weight glycoproteins, such as occur on many other bacteria, but is a natural crystal of an intrinsic membrane protein of 40,000 Mr. This molecule has been shown to be an anion-selective member of an extensive family of proteins ("porins") that render Gram-negative outer membranes permeable to solutes of up to approximately 650 Mr. Computer image processing reveals a trimeric channel-like structure that closely resembles other porins visualized in artificial arrays after treatment with detergents, but in a novel (p2) crystal form. This correlation provides a "missing link" between earlier structural studies based on artificial arrays of porins (of undefined physiological status), and membrane-permeabilization experiments with solubilized porins (in undefined structural states). For the strains characterized so far, crystallinity of the porin surface lattice shows an intriguing correlation with nonpathogenicity. PMID- 2903250 TI - Apical membrane endocytosis via coated pits is stimulated by removal of antidiuretic hormone from isolated, perfused rabbit cortical collecting tubule. AB - Antidiuretic hormone increases the water permeability of the cortical collecting tubule and causes the appearance of intramembrane particle aggregates in the apical plasma membrane of principal cells. Particle aggregates are located in apical membrane coated pits during stimulation of collecting ducts with ADH in situ. Removal of ADH causes a rapid decline in water permeability. We evaluated apical membrane retrieval associated with removal of ADH by studying the endocytosis of horseradish peroxidase (HRP) from an isotonic solution in the lumen. HRP uptake was quantified enzymatically and its intracellular distribution examined by electron microscopy. When tubules were perfused with HRP for 20 min in the absence of ADH, HRP uptake was 0.5 +/- 0.3 pg/min/micron tubule length (n = 6). The uptake of HRP in tubules exposed continuously to ADH during the 20-min HRP perfusion period was 1.3 +/- 0.8 pg/min/micron (n = 8). HRP uptake increased markedly to 3.2 +/- 1.1 pg/min/micron (n = 14), when the 20-min period of perfusion with HRP began immediately after removal of ADH from the peritubular bath. Endocytosis of HRP occurred in both principal and intercalated cells via apical membrane coated pits. We suggest that the rapid decline in cortical collecting duct water permeability which occurs following removal of ADH is mediated by retrieval of water permeable membrane via coated pits. PMID- 2903252 TI - Preliminary X-ray study of papD crystals from uropathogenic Escherichia coli. AB - The product of the Escherichia coli papD gene is a periplasmic transport protein that forms complexes with pilus subunits, thereby stabilizing them as they cross the periplasmic space to the site of pilus assembly. Purified PapD protein was crystallized by the hanging drop method of vapour diffusion with polyethylene glycol 8000 as the precipitating agent at pH 6.5. The space group is P2(1)2(1)2(1), with unit cell dimensions of a = 67.0 A, b = 58.1 A and c = 64.0 A. The crystal data, together with a subunit molecular weight of 24,500 suggest that there is one monomer in the asymmetric unit. The crystals are stable in X rays and diffract to a resolution beyond 2.0 A. PMID- 2903253 TI - X-ray-induced changes in gene expression in normal and oncogene-transformed rat cell lines. AB - As an approach to identifying specific cellular markers for the cytotoxic action of x rays in mammalian cells, we used the QUEST system of high-resolution, two dimensional protein gel electrophoresis and a computerized data base on proteins to score quantitative changes in patterns of protein synthesis. We measured the responses elicited after x irradiation of cells from the normal rat cell line REF52 as well as two oncogene-transformed REF52 cell lines with E1a or E1a plus the mutated c-Harvey-ras T24 (HRAS1 T24) allele. The transformed cell lines differed substantially in the patterns of changes in protein synthesis seen immediately after DNA damage. In addition, we identified a specific subset of growth-regulated cellular polypeptides that are correlated with the observed increase in x-ray-induced cell killing in the transformed cell lines. One of these polypeptides was cyclin (proliferating-cell nuclear antigen), a cell-cycle specific DNA polymerase delta auxiliary factor. Synthesis of this set of coregulated polypeptides was rapidly suppressed by x irradiation in normal REF52 cells only. The inability of x irradiation to induce suppression of protein synthesis in cells from the transformed cell lines correlated with the increased susceptibility to x-ray-induced cell killing. This finding suggests that the cellular processes that underlie regulation of DNA-damage-induced growth arrest at the level of replicative elongation plays a role in determining the survival of x-irradiated cells. PMID- 2903254 TI - Chromosomal locations of genes encoding 2',3' cyclic nucleotide 3' phosphodiesterase and glial fibrillary acidic protein in the mouse. AB - Cyclic nucleotide phosphodiesterase (CNP) and glial fibrillary acidic protein (GFAP) are useful markers of myelin and astroglia, respectively. Two proteins with CNP activity are known to exist in brain and lymphoid tissues. They appear to be the products of several distinct but related messenger ribonucleic acid (mRNA) species. GFAP is a single protein encoded by a single mRNA. We have localized the GFAP gene to distal chromosome 11 in the mouse. There are two genetic loci identified by CNP probes, one is closely linked to the GFAP gene, and the other maps to chromosome 3. PMID- 2903255 TI - Inhibition of rumination in sheep by alpha-adrenoreceptor antagonists. AB - Rumination activity was recorded in sheep during a period of 3 h. The amount of rumination occurring in 30 min following the intravenous injection of an alpha 1 blocking drug (prazosin, 0.1 mg/kg) and an alpha 2 blocking drug (idazoxan, 0.1 mg/kg) was reduced compared with control days when saline was given. The observation that rumination can be stimulated by a rapid, intravenous dose of adrenalin was confirmed. The induction of rumination by adrenalin was prevented by these alpha-adrenoreceptor antagonists given singly or together at the dose rate mentioned. These findings are discussed in the light of knowledge that normal reticulo-ruminal motility and food intake can be inhibited by stimulation of alpha 2-adrenoreceptors. PMID- 2903256 TI - Abdominal wall defects and cryptorchidism: an animal model. AB - Intra-abdominal pressure has been implicated in the mechanism of testicular descent. Boys born with abdominal wall defects reportedly have an increased incidence of cryptorchidism. To examine this relationship further a rat model was developed. The rat testis normally descends postnatally on or about day 21. In this study newborn male rats underwent surgical excision of all anterior abdominal musculature from the umbilicus to the xiphoid, while a control group had a sham procedure. In both groups steel wire was inserted into both testes as radiological markers to monitor descent. Animals were explored on day 28 to confirm the position of the testes. A total of 36 animals survived all sections of the protocol. Eight animals had adhesions and were dropped from the study. The results of 17 rats in the experimental group and 11 in the control group revealed that the surgically created abdominal wall defect did not result in cryptorchidism. This finding suggests that an intact anterior abdominal wall is not a prerequisite for testicular descent in the rat. PMID- 2903257 TI - Acquired undescended (ascended) testis: effects of human chorionic gonadotropin. AB - A total of 7 boys 4 to 10 years old was evaluated for undescended testes. All patients had been seen previously by a pediatric urologist and diagnosed as having a retractile testis. In fact 4 boys had undergone surgical correction of a contralateral undescended testis at an earlier date at which time the testis in question could be manipulated into the scrotum. Another boy was examined under anesthesia and the operation was canceled because the testis could be brought into the scrotum. Subsequently, on followup evaluation 2 to 8 years later the ipsilateral testis could not be manipulated into the scrotum. Of the boys 6 then were treated with a short course of human chorionic gonadotropin. Four patients had a positive response but in 3 the testis was undescended again at examination 6 months later. Of the boys 6 ultimately underwent orchiopexy. Boys with highly retractile testes require periodic examination until puberty to ensure that those testes do not ascend secondarily. PMID- 2903258 TI - The role of the gubernaculum in testicular descent. AB - The proximal and distal attachments of the gubernaculum were severed in neonatal rats to examine their role in testicular descent and their relationship to transection of the genitofemoral nerve, which prevents descent of the testis. In 34 of 82 animals proximal transection of the gubernaculum resulted in descent of the testis. In 18 animals the testis remained in the abdomen but in both groups the processus vaginalis developed, suggesting that failure of descent was accidental and not caused by scrotal maldevelopment. Distal transection resulted in failure of descent and prevented growth of the processus vaginalis in all 27 rats. These results suggest that distal transection of the gubernaculum is equivalent to division of the genitofemoral nerve, which supplies the gubernaculum through its distal attachment. Because denervation of the gubernaculum prevents the effect of androgens on gubernacular differentiation, the results suggest that testosterone acts via the nerve. The putative effect of androgens on the gubernaculum may be mediated indirectly by the central nervous system, rather than directly on the gubernaculum itself. PMID- 2903259 TI - Epididymal and vas deferens immaturity in cryptorchidism. AB - Cryptorchidism is associated with impaired spermatogenesis and, at times, sterility. Early orchiopexy has been advocated as a possible means to prevent spermatogenic impairment and infertility in patients with cryptorchidism. This retrospective study is derived from data obtained from 74 cases that were observed during a period of approximately 10 years at our hospital. Particular attention was devoted to epididymal and vas deferens histological status. Of the 47 epididymides and vas deferens examined only 2 epididymides and 2 vas deferens showed histological maturity. The remainder showed varying degrees of immaturity that additionally correlated, when testicular tissue was available, with the presence of unfavorable testicular histological findings. Cryptorchidism is associated with changes in the gonads and spermatic duct system. PMID- 2903260 TI - Psychoactive medication use in intermediate-care facility residents. AB - Despite the large number of elderly patients in nursing homes and the intensity of medication use there, few current data are available on patterns of medication use in this setting. We studied all medication use among 850 residents of 12 representative intermediate-care facilities in Massachusetts. Data on all prescriptions and patterns of actual use were recorded for all patients during one month. On average, residents were prescribed 8.1 medications during the month (interquartile range, 7.4 to 8.8) and actually received 4.7 (range, 4.2 to 5.4) medications during this period. More than half of all residents were receiving a psychoactive medication, with 26% receiving antipsychotic medication. Twenty eight percent of patients were receiving sedative/hypnotics during the study month, primarily on a scheduled rather than an as-needed basis. Of patients receiving a sedative/hypnotic, 26% (range, 14% to 41%) were taking diphenhydramine hydrochloride, a strongly anticholinergic hypnotic. Of those receiving one of the benzodiazepines, 30% were receiving long-acting drugs, generally not recommended for elderly patients. The typical benzodiazepine dose was equivalent to 7.3 mg per patient per day of diazepam. The most commonly used antidepressant was amitriptyline hydrochloride, the most sedating and anticholinergic antidepressant in common use. These data indicate that despite growing evidence of the risks of psychoactive drug use in elderly patients, the nursing home population studied was exposed to high levels of sedative/hypnotic and antipsychotic drug use. Suboptimal choice of medication within a given class was common, and use of standing vs as-needed orders was often not in keeping with current concepts in geriatric psychopharmacology. Additional research is needed to assess the impact of such drug therapy on cognitive and physical functioning, as well as to determine how best to improve patterns of medication use in this vulnerable population. PMID- 2903261 TI - [A clinical and experimental study on potentiation with sevoflurane of neuromuscular blocking effects of vecuronium and pancuronium]. PMID- 2903262 TI - Sulfated homopolysaccharides with immunomodulating activities are more potent anti-HTLV-III agents than sulfated heteropolysaccharides. AB - We reported previously that homopolysaccharides with sulfate groups revealed immunomodulating activities--lymphocyte mitogens. We further investigated the role of homopolysaccharides in a different system--cultivation of Molt-4. clone no.8 with supernatant from human T cell lymphotropic virus type III (HTLV-III) infected TALL-1, utilizing cytopathic effects (CPE), fluorescence antibody technique (FAT), reverse transcriptase (RT) assay and cell proliferation assay. Sulfated homopolysaccharides such as fucoidan, dextran sulfate with three different molecular weights, cellulose sulfate and k-carrageenan showed most potent anti-HTLV-III activities at mitogenic doses. However, neutral homopolysaccharides had no effects on anti-HTLV-III activities Sulfated heteropolysaccharides such a heparin and heparan sulfate had a little effect on anti-HTLV-III activities. It is suggested that sulfate group is most important in inhibiting growth of HTLV-III, but the structure of the polysaccharides is also important, because homopolysaccharides are more potent anti-HTLV-III agents than heteropolysaccharides. PMID- 2903263 TI - Effects of atenolol and some other beta-adrenoceptor blocking agents on norepinephrine-induced responses in isolated and perfused rat hearts. AB - The effects of atenolol and another three beta-adrenoceptor blocking agents on norepinephrine (NE)-induced cardiac responses were examined in isolated and perfused rat hearts following a Langendorff method. Bolus injection of atenolol did not show significant inhibitory effects on NE-induced increases in myocardial contractile force (MCF) and heart rate. Bolus injections of metoprolol and timolol were also ineffective for inhibiting NE-responses. However, both bolus injection and infusion of propranolol or infusion of atenolol, metoprolol and timolol all significantly inhibited NE-responses. On sustained increase in MCF induced by infusion of NE, the inhibitory effect of atenolol was transient, while that of propranolol was continuous. From these results, it is concluded that atenolol displays a different time course of action on NE-induced cardiac responses by bolus injection or infusion because of its pharmacological properties, which may be due to its low lipophilicity. PMID- 2903265 TI - [Expression of LeX antigens in renal adenocarcinoma differentiation and the prognosis]. PMID- 2903264 TI - Inactivation of dynorphin-(1-8) in isolated preparations by three peptidases. AB - Inactivation of dynorphin-(1-8) in three in vitro isolated preparations, guinea pig ileum, mouse vas deferens and rabbit vas deferens, was estimated by employing the relatively specific inhibitors of enkephalin-hydrolyzing enzymes. All three enzyme inhibitors, amastatin, captopril and phosphoramidon, significantly enhanced the inhibitory potency of dynorphin-(1-8) in the three isolated preparations. The magnitude of the enhancement of the dynorphin potency by captopril was significantly higher than that by either amastatin or phosphoramidon in guinea-pig ileum; that by amastatin was significantly higher than that by either captopril or phosphoramidon in rabbit vas deferens; and that by amastatin was similar to that by captopril, but significantly higher than that by phosphoramidon in mouse vas deferens. The Ke values of three antagonists, naloxone, Mr 2266 and ICI 154129, against dynorphin-(1-8) in the presence of the three peptidase inhibitors indicated that dynorphin-(1-8) acted on kappa receptors in guinea-pig ileum and on both kappa and delta receptors in mouse vas deferens. Since amastatin, captopril and phosphoramidon produced the naloxone reversible inhibition of contractions of guinea-pig ileum in the presence of dynorphin-(1-8), all three dynorphin-inactivating enzymes were indicated to be located very close to kappa receptors. PMID- 2903266 TI - Renal tubular actions of antihypertensive agents. PMID- 2903267 TI - Therapeutic effect and complication profile of clonidine-beta-blocker combinations. PMID- 2903268 TI - The use of recombinant DNA techniques for the diagnosis of familial hypercholesterolaemia. AB - In the UK, about 5% of patients with familial hypercholesterolaemia have a detectable deletion or rearrangement of part of the LDL-receptor gene. This results in the detection of shorter or abnormal sized fragments of the LDL receptor gene in a Southern blot hybridization. This can be used to follow the inheritance of the defective gene, and for diagnosis in the families of these individuals. In the families of the rest of the patients, diagnosis may be possible using linked restriction fragment length polymorphisms (RFLPs) detected with the LDL-receptor probe. There are now ten common RFLPs of the LDL-receptor gene, with variable sites in the 3' half of the gene. Over 80% of patients are heterozygous for at least one of these RFLPs, and therefore potentially informative for DNA diagnosis. For a foetus at risk of homozygous familial hypercholesterolaemia, antenatal diagnosis may also be possible using these methods. However, family studies require samples to be available from affected or unaffected relatives of the patient, and this limits the applicability of the tests. For some mutations, the base pair change causing the defect in the LDL receptor itself creates or destroys a site for a restriction enzyme. Such 'mutation-specific' RFLPs could be used for population screening, but so far have only been reported for the familial hypercholesterolaemia mutation that is common in Lebanon. In the future it may be possible to develop mutation-specific oligonucleotide probes for the diagnosis of familial hypercholesterolaemia. These would be appropriate for population screening or screening patients with hyperlipidaemia. This information may be useful if different mutations require different therapeutic strategies. PMID- 2903269 TI - The subcellular metabolism of glyoxylate in primary hyperoxaluria type 1: the relationship between glycine production and oxalate overproduction. PMID- 2903271 TI - Management of the HIV-infected patient. PMID- 2903270 TI - Depletion and repopulation of lymphocytes in Peyer's patches of mice after total lymphoid irradiation. AB - The depletion and repopulation of lymphocytes in specific cellular domains of mouse Peyer's patches were examined following total lymphoid irradiation (TLI). BALB/c mice 5-months-old were given 17 fractionated doses of irradiation to a total of 3400 to 4250 rads over a 4-week period, and Peyer's patches were examined by immunohistochemistry at 1 to 4 days and 1 to 4 weeks after TLI. Cryostat sections were labeled with monoclonal antibodies directed against B220 (B cells), Thy-1.2 (all T cells), L3T4 (helper T cells), and Ly-2 (cytotoxic/suppressor T cells). In depleted mice, Peyer's patches were greatly reduced in size in comparison to controls, although the structural framework of follicles, domes, and interfollicular areas was still present. B cells in follicles were reduced to a small core of B220+ cells interspersed with nonlymphocytic cells. T cells were virtually eliminated from the patch except for a small population of Thy-1.2+ cells that were neither L3T4+ nor Ly-2+ in follicle domes. During early stages of repopulation at 1 to 2 weeks after TLI, follicles increased in size and were populated by helper T cells but Peyer's patches lacked discrete interfollicular T cell regions. At 3 to 4 weeks after TLI, T cell regions were found in interfollicular areas. The results indicate that morphologically distinct cellular domains are maintained in Peyer's patches after TLI which are sequentially repopulated by immigrating lymphocytes. PMID- 2903272 TI - Comparison of three commercial amphetamine immunoassays for detection of methamphetamine, methylenedioxyamphetamine, methylenedioxymethamphetamine, and methylenedioxyethylamphetamine. AB - Three commercial immunoassays for detection of amphetamines in urine, Abuscreen radioimmunoassay (RIA), enzyme-multiplied immunoassay technique (EMIT), and the TDx fluorescence polarization immunoassay (FPIA), have been investigated for detection of methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4 methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDE). Blank urine was spiked with 0.1 to 3000 micrograms/mL amphetamine analog and used as sample in the assays. With the RIA and FPIA, MDA displayed a higher cross-reactivity to amphetamine than other analogs, but with EMIT, methamphetamine was relatively similar to amphetamine while MDA, MDMA, and MDE were less reactive. The high specificity RIA and the EMIT confirmation reagents for urine amphetamines produced significant, but relatively minor, reduction in the detectability of these analogs. The variation in cross-reactivity seen between the different assays suggests that RIA, EMIT, and FPIA antibodies have different recognition sites; however, all three immunoassays do detect the illicit amphetamine analogs to varying degrees. PMID- 2903273 TI - A rare restriction enzyme site polymorphism in the breakpoint cluster region (bcr) of chromosome 22. AB - Detection of rearrangement of the breakpoint cluster region (bcr) of chromosome 22 by Southern blot analysis can be used for the routine diagnosis of CML. Restriction fragment length polymorphisms (RFLPs) in the bcr can potentially be confused with translocation since both alter the size of DNA fragments obtained. By digesting DNA with the restriction enzyme BamHl and analyzing with probes commonly used for identifying rearrangement of the bcr, we have observed a RFLP within the bcr. For one CML patient studied in detail, the presence of the polymorphism was confirmed by comparing the results of analyses of granulocytes and a T cell-enriched population. The same polymorphism was detected in three additional CML patients and a patient with thrombocytosis. For the diagnosis of CML, verification of rearrangement with multiple probes and/or restriction enzyme combinations is necessary to rule out false positives, as well as to reduce the chance of false negatives due to co-migration of DNA fragments. PMID- 2903274 TI - [The ethical dilemma of intensive care units is not solved by the limitation of resources]. PMID- 2903275 TI - [The Wenner-Gren symposium and meeting of the Swedish Medical Society: genetics of neuropsychiatric disease]. PMID- 2903276 TI - Mother-to-child transmission of HIV infection. The European Collaborative Study. AB - 271 children born to HIV-infected mothers in 8 European centres are being followed up from birth in a multicentre, collaborative study. By June, 1988, 45% had been followed for over 1 year: 10 had developed AIDS or AIDS-related complex, all by the age of 9 months, of whom 5 had died. 22 other children had symptoms or signs suggestive of HIV infection; of these, 12 had immunological abnormalities, 9 of whom were infected. 5 children had problems not related to HIV, including 3 neonatal deaths. The other 234 children are immunologically normal and clinically well. The median age of antibody loss was 10.3 months, although 1 did not lose antibody until over 18 months. None lost antibody and then became and remained seropositive. Of 100 children followed for more than 15 months, 19 had persistent antibody, and 5 were antibody-negative but presumed to be infected because of virus isolation or antigen detection; these 5 children were clinically and immunologically normal. The estimated vertical transmission rate was 24%. PMID- 2903277 TI - Epidemiology, clinical features, and prognostic factors of paediatric HIV infection. Italian Multicentre Study. AB - 486 children born to HIV-positive mothers, 57 children infected by blood products, and 1 child for whom the personal history was not available were studied. Perinatal infection had a more varied clinical picture and a worse outcome compared with infection acquired later in childhood. Severe secondary infections, neurological disorders, and hepatitis (but not lymphoid interstitial pneumonia) were linked to a high mortality rate in perinatally infected children, in whom an early onset of symptoms was also a bad prognostic factor. Perinatal HIV infection occurred in 32.6% of children born to seropositive mothers, with a higher transmission rate in children born by vaginal delivery and then breast fed. Preterm delivery and low birthweight seemed to be related to drug abuse during pregnancy, not to intrauterine HIV infection. Girls had a higher rate of perinatal infection and, of those infected, had an increased mortality. PMID- 2903278 TI - Dietary calcium and risk of hip fracture: 14-year prospective population study. AB - To assess the effect of dietary calcium intake on risk of hip fracture, a geographically defined caucasian population in southern California was studied prospectively. Between 1973 and 1975, a quantified 24 hour diet recall was obtained by a dietician from 957 men and women aged 50 to 79 years at baseline. Follow-up to 1987 with mortality records and interviews showed 15 men and 18 women with hip fractures. The age-adjusted risk of hip fracture was inversely associated with dietary calcium whether considered as mg per day or as nutrient density (mg per 1000 kcal). No other nutrient was consistently associated with hip fracture in any Cox proportional hazards model that included calcium. The association between calcium and fracture persisted after adjustment for cigarette smoking, alcohol intake, exercise, and obesity. The significant independent inverse association of dietary calcium with subsequent risk of hip fracture (relative risk = 0.6 per 198 mg/1000 kcal) strongly supports the hypothesis that increased dietary calcium intake protects against hip fracture. PMID- 2903279 TI - Severe exercise hypoxaemia with normal or near normal X-rays: a feature of Pneumocystis carinii infection. AB - To find out whether Pneumocystis carinii pneumonia (PCP) can be detected while still in an early phase by the degree of exercise-induced oxygen desaturation, arterial oxygen saturation was measured by continuous pulse oximetry in patients positive for antibody to the human immunodeficiency virus and clinically suspected of having PCP, in patients with other chest diseases, and in controls. Among patients with proven PCP 94% of those with low arterial oxygen pressures (PaO2) showed desaturation on exercise oximetry, as did 80% of those with a normal oxygen pressure at rest, whereas only 10% of patients with other chest disorders and HIV disease showed significant desaturation. PMID- 2903280 TI - Semen analysis of patients who had orchidopexy at or after seven years of age. AB - Semen analysis was performed in 142 men who had undergone orchidopexy at age 7-13 1/2 years, 119 for unilateral cryptorchidism and 23 for bilateral cryptorchidism. Fertility potential was related to the original position of the testes: most men who had had unilateral cryptorchidism or bilateral undescended testes in the superficial inguinal pouch produced normal or acceptable semen, whereas those who had had bilateral canalicular or abdominal testes were azoospermic. PMID- 2903281 TI - Identification of a T cell lymphoma category derived from intestinal-mucosa associated T cells. AB - 2 cases of precursor T cell lymphoma and 37 cases of peripheral T cell lymphoma were investigated for their reactivity with the monoclonal antibody (mAb) HML-1, which recognises human intestinal T lymphocytes but not lymph-node T cells. In all but one of the lymphomas studied, the tumour cells were unreactive with the mAb HML-1. The HML-1+ lymphoma was the only tumour that was primarily localised in the epithelium and lamina propria of the small intestine, and was associated with ulcerative jejunitis and coeliac disease. This result suggests that the HML 1+ lymphoma was derived from intestinal mucosa T lymphocytes and differs from precursor T cell lymphoblastic lymphomas and nodal and cutaneous peripheral T cell lymphomas. PMID- 2903282 TI - Vertical transmission of HIV. PMID- 2903283 TI - Blepharospasm. PMID- 2903284 TI - Lessons from nomifensine. PMID- 2903285 TI - Survival in cystic fibrosis--how important is nutrition? PMID- 2903286 TI - Surgery for tricuspid regurgitation. PMID- 2903287 TI - Scrub typhus pneumonia. PMID- 2903288 TI - Causes of arthritis. PMID- 2903289 TI - Are current dietary guidelines for young children a prescription for overfeeding? AB - New estimates for the energy requirements of young children have been derived by combining the energy deposited during growth with measurements of total energy expenditure obtained by use of the new doubly-labelled water (2H2(18)O) method in 355 healthy infants aged 0-3 years. The resultant values of 110, 95, 85, 83, 83, 84, and 85 kcal/kg/day at 1, 3, 6, 9, 12, 24, and 36 months, respectively, are substantially lower than current Department of Health and Social Security and FAO/WHO/UNU recommended dietary allowances. Evidence from diet surveys suggests that changes in infant feeding practices are largely responsible for the apparent reduction in energy requirements. Dietary guidelines may need to be reappraised, to avoid overfeeding of infants. PMID- 2903290 TI - Adoption and genetic prediction for Huntington's disease. PMID- 2903291 TI - Beta-haemolytic streptococci group A in a cat, as a possible source of repeated tonsillitis in a family. PMID- 2903292 TI - Symptom substitution in Tourette disorder. PMID- 2903294 TI - Reye's syndrome in children travelling abroad. PMID- 2903293 TI - Treatment of acute graft-versus-host disease with monoclonal antibody to IL-2 receptor. PMID- 2903295 TI - Salmonellosis and eggs. PMID- 2903296 TI - Dexamethasone-induced bradycardia. PMID- 2903297 TI - Predictive value of HIV replication in cell culture in babies born to HIV seropositive mothers. PMID- 2903298 TI - Kaposi's sarcoma in homosexual men with AIDS, by race. PMID- 2903299 TI - Post-mortem neuropathological studies in AIDS. PMID- 2903300 TI - Adenoidal hypertrophy in HIV-infected patients. PMID- 2903302 TI - Economy class syndrome. PMID- 2903301 TI - Thermal burns, gender, and survival. PMID- 2903303 TI - Hypovitaminosis a of follicular duct as cause of acne vulgaris. PMID- 2903304 TI - Examining surgeons. PMID- 2903305 TI - Teaching and training of invasive procedures on cadavers. PMID- 2903306 TI - Cycads and amyotrophic lateral sclerosis/parkinsonism dementia. PMID- 2903307 TI - Adverse reactions reporting and age. PMID- 2903308 TI - Embryopathy in infant conceived one year after termination of maternal etretinate. PMID- 2903309 TI - Coronary heart disease prevention. PMID- 2903310 TI - Clinical/subclinical case ratio in hepatitis A. PMID- 2903311 TI - ACE inhibitors. PMID- 2903312 TI - Categories of drug allergy. PMID- 2903313 TI - Drug expiry dates, storage, and potency. PMID- 2903314 TI - Nebulised ribavirin for influenza B viral pneumonia in a ventilated immunocompromised adult. PMID- 2903315 TI - Prenatal diagnosis of cystic fibrosis where single affected child has died: Guthrie spots and microvillar enzyme testing. PMID- 2903316 TI - Screening for toxoplasma in pregnancy. PMID- 2903317 TI - Pneumococcaemia caused by erythromycin-resistant Streptococcus pneumoniae type 14. PMID- 2903318 TI - Thromboembolic events during combination chemotherapy for germ cell-malignancy. PMID- 2903320 TI - NIH finds research on fetal tissue "acceptable". PMID- 2903319 TI - Multiple pregnancy, selective reduction, and flexible treatment. PMID- 2903321 TI - Compensation: a draft bill. PMID- 2903322 TI - Adjuvant therapy with tamoxifen in operable breast cancer. 10 year results of the Naples (GUN) study. AB - Treatment with tamoxifen (TM), alone or in combination with cyclophosphamide, methotrexate, and fluorouracil (CMF), was used as an adjuvant to surgery in 433 patients with stage I, II, or III(T3a) breast cancer. Oestrogen receptors (ER) and progesterone (PgR) receptors were assayed in most cases. 308 premenopausal node-negative and postmenopausal node-negative or node-positive patients were randomised to receive TM, 30 mg daily for 2 years, or no further therapy. 125 premenopausal node-positive patients were randomised to receive either CMF for nine courses plus TM or CMF alone. After a median follow-up of 63 months TM significantly reduced the incidence of relapses and deaths compared with no therapy. A significant interaction between treatment effect and ER/PgR status was seen. Disease-free and overall survival were similar after treatment with CMF+ TM or CMF. PMID- 2903323 TI - Maternal immune responses to the fetus in early pregnancy and recurrent miscarriage. AB - Direct evidence that maternal immune rejection of the fetus causes some unexplained recurrent spontaneous abortions was sought in 18 women with this condition. Tests of maternal cell-mediated immunity to fetal (paternal) antigens were done before conception, in early pregnancy, and at miscarriage, and were compared with those in 10 controls in their first pregnancies. Maternal cytotoxic alloantibody production and the blocking effect of maternal sera on maternal lymphocyte activation were also evaluated. There was no evidence for maternal cell-mediated reactivity to paternal antigens in normal early pregnancy or in most women who aborted, but circulating cytotoxic cells were found at miscarriage in a third of affected women. There was no correlation between the production of cytotoxic antibodies and serum blocking activity, and the success of the pregnancy. These data provide evidence that cell-mediated immune reactivity may be changed in some women who abort recurrently but show that circulating immunological blocking factors are not relevant to the success of pregnancy. Their induction by maternal immunisation with paternal leucocytes does not explain why this procedure prevents recurrent spontaneous abortions. PMID- 2903324 TI - IgA antibodies against P30 as markers of congenital and acute toxoplasmosis. AB - Specific IgA antibodies against P30, a major surface protein of Toxoplasma gondii were sought in 198 serum samples (from 133 patients) by means of a double sandwich enzyme-linked immunosorbent assay. These antibodies were detected in all cases of acute toxoplasmosis but in no cases of chronic toxoplasmosis nor in seronegative patients. They were not detected in samples from patients with "natural IgM antibodies" or in those containing rheumatoid factor or antinuclear antibodies. Among 26 infants whose mothers were infected during pregnancy, anti P30 IgA antibodies were exclusively detected in the samples from the 8 infected infants, although anti-P30 IgM antibodies were detected in only 3 of the infected infants. No uninfected infant had IgA, though 5 had IgM at birth. Thus, the detection of IgA anti-P30 antibodies seems a better means than the detection of IgM antibodies of identifying infected infants, which is very important for treatment. In addition, the very early detection of IgA antibodies may be important for the diagnosis of acute toxoplasmosis, especially during pregnancy and perhaps also in patients infected by human immunodeficiency virus. PMID- 2903325 TI - New device to improve the accuracy of bedside blood glucose tests. AB - A new device to improve the accuracy of blood glucose measurements with glucose oxidase reagent strips is described. The device ensures that an adequate amount of blood is applied onto the reagent pad when the strip is fully inserted. When the strip is withdrawn, the pad is automatically wiped, and so the reaction can be accurately timed. The device also reduces the risk of blood contamination of other surfaces. Use of a prototype of this device enabled more accurate measurement of blood glucose on general wards. PMID- 2903327 TI - Surgery for temporal lobe epilepsy. PMID- 2903326 TI - Plasmapheresis in treatment of human T-lymphotropic virus type-I associated myelopathy. AB - In 11 of 18 patients with human T-lymphotropic virus type-I (HTLV-I) associated myelopathy (HAM) gait, sensory, and/or sphincter disturbance improved with plasmapheresis (4 to 6 sessions in 2 weeks), and the effects were maintained for 2 to 4 weeks. Plasmapheresis lowered the titre of HTLV-I antibody in serum but not in cerebrospinal fluid, and change of HTLV-I antibody titres did not correlate with the effects of plasmapheresis. These results suggest that plasmapheresis is useful treatment, at least in producing a temporary improvement, in patients with HAM, and that some humoral factor(s), but not HTLV I antibody, may be important in the pathogenesis of HAM. PMID- 2903328 TI - Of pancreas, pain, and papilla. PMID- 2903329 TI - Infant mortality. PMID- 2903330 TI - Vegetations, valves, and echocardiography. PMID- 2903331 TI - Augmentation therapy in alpha-1-antitrypsin deficiency. PMID- 2903332 TI - South American pemphigus foliaceus. PMID- 2903333 TI - Trends in unexpected infant deaths in Sheffield. AB - A study of 250 post-perinatal deaths in Sheffield during the past 8 years has shown an increased rate of unexpected infant death. This increase appears to be mainly caused by deaths in children with minor disease in families where the father is either absent or unemployed. The number of children who die during the course of more serious disease continues to fall. The number of infant deaths from other causes is unchanged. PMID- 2903334 TI - Microbiological look at urodynamic studies. AB - Urine samples were cultured for aerobic, fastidious, and anaerobic bacteria in 88 patients (66 F, 22 M) before and after standard urodynamic investigations. 37 of 42 women with detrusor instability, and 14 of 17 women with stress incontinence, had evidence of bacteriuria with aerobic or fastidious bacteria before investigation, as did 6 of 13 men with bladder outflow obstruction. 8 men (36%) acquired bacteriuria with aerobic bacteria after investigation, compared with 10 women (15%). Recalcitrant, irritative urinary symptoms in women may be caused by an underlying infection, the urodynamic changes being secondary. In men who have urodynamic studies, antibiotic prophylaxis should be considered. PMID- 2903335 TI - In praise of peroxidation. AB - Free-radical-mediated lipid peroxidation has become closely associated with destructive biochemical processes and, more recently, with disease. Its potential survival value may be overlooked. PMID- 2903337 TI - Mass vaccination against hepatitis B in infants in Italy. PMID- 2903338 TI - Materno-fetal listeriosis from cook-chill and refrigerated food. PMID- 2903336 TI - The rights of the patient in clinical research. PMID- 2903339 TI - Salmonella enteritidis and eggs. PMID- 2903340 TI - Naloxone for septic shock. PMID- 2903341 TI - Laboratory techniques and neuroblastoma screening. PMID- 2903342 TI - Thalidomide for graft-versus-host disease. PMID- 2903343 TI - Cytomegalovirus infection and renal transplantation. PMID- 2903344 TI - Infant feeding and childhood cancer. PMID- 2903345 TI - Handgun availability and firearm mortality. PMID- 2903346 TI - Ganciclovir for severe cytomegalovirus infection in transplant recipients. PMID- 2903347 TI - Changing criteria for mild hypertension: effect on number of patients treated. PMID- 2903348 TI - Clinical use of botulinum toxin. PMID- 2903349 TI - Health promotion. PMID- 2903350 TI - Medical education. PMID- 2903351 TI - Youth and threat of nuclear war. PMID- 2903352 TI - Wearing gloves as cause of false-negative HIV tests. PMID- 2903353 TI - AIDS: who to treat? PMID- 2903354 TI - Stun-guns and snakebites. PMID- 2903355 TI - Safety of pasteurised factor VIII (haemate HS) PMID- 2903356 TI - Home treatment for deep venous thrombosis with low-molecular-weight heparin. PMID- 2903357 TI - Epoprostenol in systemic capillary leak syndrome. PMID- 2903358 TI - Teratogenicity of isotretinoin and etretinate. PMID- 2903359 TI - Local recombinant tissue plasminogen activator to clear cerebral artery thrombosis developing soon after surgery. PMID- 2903360 TI - Two-year follow-up of biphosphonate (APD) treatment in steroid osteoporosis. PMID- 2903361 TI - Cyanide and fire victims. PMID- 2903362 TI - Urology and the TNM classification. PMID- 2903363 TI - Prevalence of antibody to human herpesvirus 6 among blood donors infected with HIV. PMID- 2903364 TI - Salt, pregnancy, hypertension--and literature searches. PMID- 2903365 TI - Idiopathic thrombocytopenia treated with Paf-acether antagonist WEB 2086. PMID- 2903367 TI - Classifying primary gut lymphomas. PMID- 2903366 TI - HTLV-I antibodies in Papua New Guinea. PMID- 2903368 TI - Home measurement of blood pressure. PMID- 2903369 TI - Is Campylobacter pylori a zoonosis? PMID- 2903370 TI - Consent for vaginal examination by students on anaesthetised patients. PMID- 2903371 TI - Switching to human insulin. PMID- 2903372 TI - A disputed spleen. PMID- 2903373 TI - Mysteries of Kaposi sarcoma. PMID- 2903374 TI - ASH renews its attack on tobacco advertising. PMID- 2903375 TI - Graves' disease of the beta cell: glucose dysregulation due to islet-cell stimulating antibodies. AB - The immunoglobulin fractions of serum from patients with spontaneous hyperinsulinaemic hypoglycaemia and others with type 1 diabetes stimulated insulin release both in islet-cell cultures and in vivo in rats. Serum from patients with type 2 diabetes, which is not an autoimmune disease, did not stimulate insulin release. The discovery of islet-cell-stimulating antibodies (ICSTA) completes for the islet the triad of autoantibodies (anticytoplasmic, antiproduct, and antireceptor) previously described in autoimmune thyroid disease. ICSTA may be important modulators of islet-cell secretion in man. PMID- 2903376 TI - Persistent B19 parvovirus infection as a cause of severe chronic anaemia in children with acute lymphocytic leukaemia. AB - In two children with acute lymphocytic leukaemia in whom severe anaemia developed, serum samples collected over 9-12 months showed high concentrations of B19 parvovirus, the aertiological agent of fifth disease. In one patient, anaemia recurred with the reappearance of virus in serum; in the other, the anaemia persisted. Smears of bone marrow aspirates obtained during periods of viraemia showed giant pronormoblasts and either absent mature erythroid cells or erythroid hypoplasia. Parvovirus replication in the marrow was detected by Southern blot of cellular DNA. An underlying immune deficit was suggested by low titres of specific antibodies against B19 parvovirus. Treatment of one patient with plasma containing specific antibodies against parvovirus resulted in a transient fall in serum virus levels, the appearance of reticulocytes, and symptoms of fifth disease. PMID- 2903377 TI - Neutrophil death as a defence mechanism against Candida albicans infections. AB - In studies of experimental Candida albicans infections, growth of invading organisms sometimes ceased before the organisms reached the neutrophil infiltrates. Lysates of human neutrophils inhibited the directed growth of candida pseudohyphae in agarose gel and suppressed the proliferation of candida yeast in broth cultures, but did not kill the organisms or prevent their germination. The growth-inhibitory material released from disrupted neutrophils had an estimated molecular weight of 30 kD and differed from most previously described neutrophil antimicrobial factors in that it was present in cell sap rather than granules, and did not appear in the supernatant after stimulation of the cells. Neutrophil death and dissolution may represent an alternative host defence mechanism against invasive C albicans infection. PMID- 2903378 TI - Are antimitochondrial antibodies in primary biliary cirrhosis induced by R(rough) mutants of enterobacteriaceae? AB - Antimitochondrial antibody (AMA)-positive serum samples from 45 patients with primary biliary cirrhosis (PBC) and AMA-negative serum samples from patients with chronic liver diseases, systemic lupus erythematosus, or rheumatoid arthritis were studied by an immunoblot technique with mitochondria from bovine heart and pig kidney and with several strains of gram-negative bacteria as antigens after separation by sodiumdodecylsulphate polyacrylamide gel electrophoresis. Serum from patients with PBC recognised up to three mitochondrial antigens with molecular weights of 70 kD, 50 kD, and 42 kD. Equivalent patterns were found with bands at 70-80 kD and 50-52 kD with Enterobacteriaceae as antigens. AMA-reactive polypeptides were localised in the ribosomal and membrane fractions from Enterobacteriaceae but differed from known outer membrane proteins. Conversely, PBC-specific mitochondrial antigens at 70 kD and 50 kD were recognised by rabbit antisera against Salmonella minnesota Rb and Rc mutants but not by antisera against wild-type Enterobacteriaceae. Absorption experiments and two-dimensional immunoblotting studies confirmed that mitochondria and gram-negative bacteria share identical PBC-specific determinants. It seems that PBC-specific antigens are expressed in gram-negative bacteria and that these antigens may be immunogenic in mutants with defective polysaccharide synthesis. The data support the hypothesis of a bacterial aetiology for PBC. PMID- 2903379 TI - Effect of acute administration of insulin-like growth factor I in patients with Laron-type dwarfism. AB - Biosynthetic insulin-type growth factor I (IGF-I) was given as an intravenous bolus of 75 micrograms/kg to 9 patients with Laron-type dwarfism. Rapid onset of hypoglycaemia (-45% of basal level) was associated with a reduction in plasma insulin (-55% of basal level); thus, the lack of growth hormone receptors in this condition does not apply to IGF-I receptors and post-receptor pathways. Long-term treatment may therefore be beneficial in Laron-type dwarfism. PMID- 2903380 TI - Glucose tolerance in pregnancy--the who and how of testing. PMID- 2903381 TI - Which medical condition shall we treat first? PMID- 2903382 TI - Do patients with mild angina need surgery? PMID- 2903383 TI - The Bamako initiative. PMID- 2903384 TI - Laurence-Moon and Bardet-Biedl syndromes. PMID- 2903385 TI - Endothelin: an important factor in acute renal failure? AB - Very low concentrations of the vasoconstrictor peptide endothelin cause intense long-lasting renal vasoconstriction. In the isolated perfused rat kidney, the concentration of endothelin required to reduce blood-flow by 50% is 200 pmol/l, compared with 1000 pmol/l angiotensin II (previously the most potent known vasoconstrictor). Whereas angiotensin II has little effect on the glomerular filtration rate (GFR), a rise in endothelin from 100 to 800 pmol/l reduces GFR by 90%. Endothelin is probably present in the circulation at low concentrations in vivo; events associated clinically with acute renal failure would tend to increase this concentration. Endothelin may be a mediator in the pathogenesis of acute renal failure. PMID- 2903387 TI - Memories: a neglected concept in care. PMID- 2903386 TI - Trial of co-trimoxazole versus procaine penicillin with ampicillin in treatment of community-acquired pneumonia in young Gambian children. AB - 134 Gambian children under 5 years of age with severe pneumonia (as defined by the World Health Organisation classification of acute respiratory infections) were given either oral co-trimoxazole for 5 days, or a single intramuscular dose of fortified procaine penicillin and 5 days of oral ampicillin. At 2 weeks, there was no significant difference in outcome between the two groups. Co-trimoxazole is much less expensive than ampicillin or procaine penicillin, requires only twice-daily administration, and can be given by health-care staff with little training. The results support the use of co-trimoxazole as the antibiotic of first choice in outpatient management of young children with pneumonia in developing countries. PMID- 2903388 TI - International Physicians for the Prevention of Nuclear War: Messiahs of the nuclear age? PMID- 2903389 TI - Out-of-hospital, paramedic administered streptokinase for acute myocardial infarction. PMID- 2903390 TI - Significant reduction in mortality with streptokinase given 7-24 hours after pain onset. PMID- 2903391 TI - Aspirin and fibrinolysis. PMID- 2903392 TI - Spontaneous intermittent reperfusion in early myocardial infarction. PMID- 2903393 TI - Coronary heart disease prevention. PMID- 2903394 TI - Delayed seroconversion, Legionnaires' disease, and age. PMID- 2903395 TI - Clonidine for short stature. PMID- 2903396 TI - Akureyri disease (myalgic encephalomyelitis), forty years later. PMID- 2903397 TI - Influenza-like syndrome after terconazole. PMID- 2903398 TI - Paracetamol and peptic ulcer. PMID- 2903399 TI - Prochlorperazine and the elderly. PMID- 2903400 TI - Successful use of recombinant factor VIIa in patient with severe haemophilia A during synovectomy. PMID- 2903401 TI - Informed consent and controlled trials. PMID- 2903402 TI - Revising RAWP. PMID- 2903403 TI - Zidovudine and bone marrow. PMID- 2903405 TI - Screening for toxoplasmosis in pregnancy. PMID- 2903404 TI - Diabetes in AIDS patients. PMID- 2903406 TI - Psittacine birds and chlamydia. PMID- 2903407 TI - Semen cryopreservation for patients surviving malignant disease: implications of proposed legislation. PMID- 2903409 TI - Guillain-Barre syndrome: prognosis and pathogenesis. PMID- 2903408 TI - Von Recklinghausen neurofibromatosis and myeloproliferative disorders in adults. PMID- 2903410 TI - Screening for breast cancer. PMID- 2903411 TI - Rectal and anal pressure profile in constipated children. PMID- 2903412 TI - Creutzfeldt-Jakob disease, spiroplasmas, and crystalline artifacts. PMID- 2903413 TI - Outbreak of enterically transmitted non-A, non-B hepatitis among schoolchildren. PMID- 2903414 TI - Pathogenesis of type I diabetes. PMID- 2903415 TI - Blood testing before prescribing oral contraception in Africa. PMID- 2903416 TI - Bovine somatotropin and milk composition. PMID- 2903417 TI - Transmission of Listeria monocytogenes from mother's milk to her baby and to puppies. PMID- 2903418 TI - Magnetic resonance imaging and early diagnosis of multiple sclerosis. PMID- 2903419 TI - Early lesion of multiple sclerosis. PMID- 2903420 TI - Breastfeeding as a family planning method. PMID- 2903422 TI - AIDS in the UK. PMID- 2903421 TI - Suspended doctors in the Health Service. PMID- 2903423 TI - [Surgical therapy in the treatment concept of ulcer disease. A critical evaluation]. AB - Since the introduction of H2-receptor antagonists ulcer therapy has changed in favour of conservative management against surgery. In spite of this shift in therapy mortality from peptic ulcer did not decrease through the last three decades. Obviously conservative management does not influence the rate of ulcer complications but postpones them to the aged. Peptic ulcer surgery offers differentiated therapies for complications as well as for uncomplicated ulcer disease. In bleeding ulcers combination of therapeutic endoscopy and early elective surgery reduced mortality to 5%. Targets of therapy are both bleeding and ulcer disease. Obstruction is cured in the same way as uncomplicated ulcers with additional pyloro- or duodenoplasty. In cases of perforation the decision for simple suture or definitive treatment should be orientated to ulcer history. Due to their localisation uncomplicated ulcers are treated best by selective proximal vagotomy, combined resection or Billroth I resection. After surgery the monthly recurrence risk of uncomplicated ulcers is about ten times lower than throughout long-term conservative therapy. From the present point of view only surgery seems to be able to reduce persisting rates of ulcer mortality in the future. PMID- 2903424 TI - [Aspartate aminotransferase, alanine aminotransferase and gamma glutamyltransferase in plasma and blood donors]. PMID- 2903425 TI - Hormonal effects of CV 205-502, a novel octahydrobenzo [g] quinoline with potent dopamine agonist properties. AB - Following the success of ergot alkaloids and their synthetic derivatives in treating a variety of pathophysiological disturbances, efforts have been concentrated on the synthesis of new derivatives and partial structures with the aim of dissecting out a specifically dopaminomimetic pharmacophore. Accordingly CV 205-502, a structure which superposes the linear benzo [g] quinoline segment of apomorphine on the substituted pyrrolo [3,4- g] quinoline moiety of the ergolines was designed. This study was performed in normal young volunteers to investigate the effect of single oral doses of CV 205-502 on plasma prolactin levels and on other endocrine parameters (GH, LH, FSH, TSH and cortisol) as well as on tolerability. 10 volunteers participated in a dose-ranging study. They received single oral doses of 0.01 to 0.09 mg CV 205-502, in order to assess the prolactin suppressant action. 6 volunteers were given a dose of 0.06 mg CV 205 502 in order to determine the endocrine profile of the compound. The duration of action of 0.06 mg CV 205-502 was investigated in 6 subjects by measuring plasma PRL and GH levels for 48 h. The results show strong dose-dependent suppression of PRL appearing following doses between 0.04 and 0.09 mg of CV 205-502. PRL was markedly suppressed for more than 24h. and the peaks of the normal sleep profile were abolished. Intermittent transient GH increases occurred during the first 6 hours; sleep profiles were normal. Compared with placebo values, no changes were seen in the levels of any other hormone except TSH, which decreased. Tolerability was good and no drug attributable changes in safety measures occurred. This study demonstrates that CV 205-502 is a potent and long acting PRL suppressant compound and suggest that this novel octahydrobenzo [g] quinoline will prove to be a therapeutically useful dopaminomimetic compound. PMID- 2903426 TI - Effect of 1-methyl-4-phenylpyridinium ion (MPP+) on catecholamine levels and activity of related enzymes in clonal rat pheochromocytoma PC12h cells. AB - 1-Methyl-4-phenylpyridinium ion (MPP+), a metabolite of a neurotoxin, 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine, was found to reduce dopamine (DA) level and the activity of enzymes related to its metabolism in clonal rat pheochromocytoma PC12h cells. After 6 days' culture in the presence of 1 mM and 100 microM MPP+, DA content in PC12h cells was reduced markedly, but with MPP+ at concentrations lower than 10 microM, DA levels in the cells did not change. The amounts of 3,4 dihydrophenylacetic acid (DOPAC), a metabolite of DA were reduced markedly in culture medium and in PC12h cells cultured with MPP+ at concentrations higher than 1 microM. MPP+ was found to reduce the enzyme activity of tyrosine hydroxylase (TH), monoamine oxidase (MAO) and aromatic L-aminoacid decarboxylase (AADC). In the presence of MPP+ at concentrations higher than 10 microM, reduction of TH activity in the cells was more pronounced than reduction of cell protein or of the activity of a non-specific enzyme, beta-galactosidase. With 1 mM and 100 microM MPP+, MAO activity was reduced to about 30% of that in control cells. Reduction was observed with MPP+ at concentrations higher than 1 microM. AADC was the most sensitive to MPP+ and its activity was reduced markedly in the cells cultured with 100 nM MPP+. These results indicate that MPP+ inhibits not only the biosynthesis of catecholamines, but also the enzyme participating in their catabolism in cells, and may thus perturb catecholamine levels in the brain. PMID- 2903427 TI - Differential effects of dietary linoleic and alpha-linolenic acid on lipid metabolism in rat tissues. AB - Comparative effects of feeding dietary linoleic (safflower oil) and alpha linolenic (linseed oil) acids on the cholesterol content and fatty acid composition of plasma, liver, heart and epididymal fat pads of rats were examined. Animals fed hydrogenated beef tallow were used as isocaloric controls. Plasma cholesterol concentration was lower and the cholesterol level in liver increased in animals fed the safflower oil diet. Feeding the linseed oil diet was more effective in lowering plasma cholesterol content and did not result in cholesterol accumulation in the liver. The cholesterol concentration in heart and the epididymal fat pad was not affected by the type of dietary fatty acid fed. Arachidonic acid content of plasma lipids was significantly elevated in animals fed the safflower oil diet and remained unchanged by feeding the linseed oil diet, when compared with the isocaloric control animals fed hydrogenated beef tallow. Arachidonic acid content of liver and heart lipids was lower in animals fed diets containing safflower oil or linseed oil. Replacement of 50% of the safflower oil in the diet with linseed oil increased alpha-linolenic, docosapentaenoic and docosahexaenoic acids in plasma, liver, heart and epididymal fat pad lipids. These results suggest that dietary 18:2 omega 6 shifts cholesterol from plasma to liver pools followed by redistribution of 20:4 omega 6 from tissue to plasma pools. This redistribution pattern was not apparent when 18:3 omega 3 was included in the diet. PMID- 2903428 TI - Techniques of benzodiazepine withdrawal in clinical practice. A consensus workshop report. AB - This is a report of a consensus conference on the management of the benzodiazepine-dependent patient. While the focus is on patients who are already dependent, it is better to avoid dependence in therapeutic use by careful patient selection, low dose and short term administration. The management of dependence can normally be undertaken in general practice unless there are complicating factors, e.g. concomitant severe medical, psychiatric or social problems. Inpatient management is also preferable for those abusing drugs in the sociorecreational area. Withdrawal should be achieved by gradual dosage reduction over a period of several weeks. Support from the practitioner, family and friends is important to achieve good results. Since postwithdrawal problems occur, good clinician support is necessary over at least the next year. Despite the risk of dependence, it is stressed that benzodiazepines are valuable therapeutic agents for several psychiatric and physical disorders. PMID- 2903429 TI - Value of flumazenil in benzodiazepine self-poisoning. AB - The efficacy of the benzodiazepine-antagonist flumazenil (Ro 15-1788) was evaluated in 26 patients with coma due to benzodiazepine self poisoning, alone or in combination with alcohol or other psychoactive drugs. 77% of the patients responded to the administration of a mean dose of 1.73 mg (range 0.2 to 8 mg) with immediate awakening or an improvement of at least 2 coma grades. In the patients without response (n = 3) or with minor improvement (n = 3) other psychoactive drugs turned out to be predominantly responsible for their comatose state. Adverse effects of flumazenil treatment such as altered blood pressure or increased heart rate were observed, but were generally mild. An acute benzodiazepine withdrawal syndrome was seen in 2 cases. In conclusion, flumazenil proved to be effective in the treatment of severe benzodiazepine intoxication. Beyond that, in cases of mixed overdosage or initially unknown diagnosis the antidote assisted in the clarification of the clinical condition. PMID- 2903430 TI - On the measurement of lactate turnover in humans. AB - It has been shown in studies of turnover in vivo of lactate and several amino acids that the specific activity in blood depends on the site of tracer administration and of sampling. Theoretical and experimental studies have established that to obtain valid estimation of turnover in vivo for these compounds, tracers should be administered into the left heart, ideally the ventricle, and blood sampled from the right heart, ideally the pulmonary artery. Alternately, tracer may be infused into the pulmonary artery and blood sampled from the right ventricle. The insertion of such in-dwelling catheters for turnover studies is difficult in small animals and not justified on ethical grounds in humans. We describe here a method to calculate valid turnover rates when the tracer is administered in a peripheral vein and blood sampled from any peripheral artery. In humans, infusion into a hand vein and sampling from the contralateral heated hand vein can be used. The true turnover rate can then be calculated if the cardiac output is determined. Several noninvasive methods for the determination of cardiac output are available. Thus a correct estimate, avoiding major catheterization, for turnover for many blood-borne compounds is possible. PMID- 2903431 TI - Blood-conservation techniques for coronary-artery bypass surgery at a private hospital. AB - The utilization of homologous blood and blood products was recorded in 100 consecutive patients who underwent primary coronary-artery bypass surgery. Nine patients underwent saphenous-vein grafts only, 55 patients underwent a single internal-mammary-artery graft that was supplemented by vein grafts and 36 patients underwent bilateral internal-mammary-artery grafts and vein grafts. All patients underwent normovolaemic haemodilution, and autologous blood was collected before bypass surgery. Residual blood was collected from the cardiopulmonary bypass machine and was washed and concentrated in a cell processor, and blood also was scavenged postoperatively from the mediastinal drainage tubes as methods to conserve blood. The mean (+/- SD) utilization of homologous blood was 1.3 +/- 1.5 units with 0.2 +/- 0.7 units of fresh-frozen plasma being used, and 0.8 +/- 2.1 units of platelets being used. The utilization of homologous blood was not different among the three different methods of coronary-artery bypass surgery, but patients who underwent bilateral internal mammary-artery grafts suffered a greater postoperative loss of blood than did those patients who underwent saphenous-vein grafts or single internal-mammary artery grafts. A comparison of patients who were taking aspirin or a non steroidal anti-inflammatory drug preoperatively with those patients who were not showed no difference in the utilization of homologous blood but a statistically significant difference was found in the loss of blood postoperatively. PMID- 2903432 TI - [Surface necroses of the skin following sulfasalazine therapy in ulcerative colitis]. PMID- 2903433 TI - Changes in glutamate-cycle enzyme mRNA levels in a rat model of hepatic encephalopathy. AB - To detect possible changes in the regulation of glutamate/gamma-aminobutyric acid (GABA) enzymes at the level of gene expression in a thioacetamide-induced rat model of acute hepatic encephalopathy, we have examined changes in the mRNAs of four glutamate/GABA enzymes by quantitative RNA blot hybridization analysis. Such changes could reflect cell adaptation to excess ammonia or some other associated metabolic stress. The mRNA levels of glutamate dehydrogenase (GDH) decreased similarly in three different brain regions, whereas those of glutamine synthetase (GS) and glutaminase (GA) increased. The mRNA levels of glutamate decarboxylase (GAD) were unchanged. The results indicate that some effect of liver damage, presumably hyperammonemia, affected the expression of some, but not all, genes associated with ammonia and glutamate metabolism in the brain. This adaptation of gene expression to secondary effects of ammonia on brain amino acid neurotransmitter metabolism or brain energy metabolism could play a role in the physiological changes observed in hepatic encephalopathy. PMID- 2903435 TI - The aspartate transcarbamylase domain of a mammalian multifunctional protein expressed as an independent enzyme in Escherichia coli. AB - Although aspartate transcarbamylase (ATCase) is an independent, monofunctional enzyme in Escherichia coli, mammalian ATCase is one of the globular enzymatic domains of the multifunctional CAD protein. We subcloned fragments of the hamster CAD cDNA and assayed polypeptide products expressed in E. coli for ATCase activity in order to isolate a stretch of cDNA which encodes only the ATCase domain. Three such expression constructs contain fragments of hamster CAD cDNA similar in length to the gene encoding the E. coli ATCase catalytic subunit (pyrB). These constructs yield stable proteins with ATCase activity, ascertained by both in vivo and in vitro assays; the clones also possess sequence homology with the pyrB gene at both the 5' and 3' ends. The clone producing the most active ATCase contains cDNA which is analogous to the entire pyrB gene, plus a small amount of CAD sequence upstream of this region. Because these constructs produce independently folded, active ATCase from a piece of cDNA the size of the E. coli pyrB gene, they open the door for the in-depth investigation of the isolated mammalian enzyme domain utilizing recombinant DNA technology. This approach is potentially useful for the analysis of domains of other multifunctional proteins. PMID- 2903434 TI - Genetic mechanisms of bacterial antigenic variation. PMID- 2903436 TI - A common trans-acting factor is involved in transcriptional regulation of neurotransmitter genes by cyclic AMP. AB - Activation of neurotransmitter receptors can regulate transcription in postsynaptic cells through the actions of second messengers. Trans-synaptic regulation of transcription appears to be an important mechanism controlling the synthesis of molecules involved in neuronal signaling, especially neuropeptides. Proenkephalin, vasoactive intestinal polypeptide, and somatostatin have been shown to be transcriptionally regulated by the second messenger, cyclic AMP (cAMP), as has the catecholamine synthesizing enzyme tryosine hydroxylase. cAMP inducible elements have been mapped within these genes, and trans-acting factors which bind to several such elements have been identified. With the discovery that individual neurons generally contain multiple transmitters within their synaptic terminals, it has become important to understand in detail the mechanisms by which the synthesis of transmitters can be coregulated. Here we compare the structure and function of the proenkephalin cAMP-inducible enhancer with the mapped cAMP-inducible elements of the vasoactive intestinal polypeptide, somatostatin, and tyrosine hydroxylase genes and a putative cAMP-inducible element in the proto-oncogene c-fos. We have previously shown that the proenkephalin enhancer is composed of two different elements, ENKCRE-1 and ENKCRE 2. We show here that one of these, ENKCRE-2, is structurally similar to elements found within the vasoactive intestinal polypeptide, somatostatin, and tyrosine hydroxylase genes and binds a trans-acting factor that is competed for both in cotransfection experiments (in vivo) and in DNase I footprint assays (in vitro) by these other elements. The c-fos element has similar structural requirements to confer transcriptional induction by cAMP but competes less strongly. Protein purified by affinity chromatography with the ENKCRE-2 sequence binds to each of these elements. A second element within the proenkephalin cAMP-inducible enhancer, ENKCRE-1, binds a factor that is not competed for by these other genes and is therefore distinct. This analysis suggests a potential mechanism of transcriptional coregulation of the neuronally expressed genes investigated in this study and also demonstrates that multiple factors are involved in transcriptional activation by cAMP. PMID- 2903438 TI - Identification of a rat c-erbA alpha-related protein which binds deoxyribonucleic acid but does not bind thyroid hormone. AB - c-erbA cDNAs encoding thyroid hormone-binding receptor proteins have been previously isolated from several species and tissues. We have isolated a novel rat c-erbA cDNA, r-erbA alpha-2, identical to the rat brain c-erbA alpha cDNA (which we refer to as r-erbA alpha-1) except at the 3'-end of the cDNA, which encodes an altered carboxy-terminal region of the predicted amino acid sequence. The r-erbA alpha-2 cDNA is most closely related to the human testicular c-erbA alpha cDNA. The apparent molecular weight of the in vitro protein product of this cDNA is 55 K, close to that predicted from the nucleotide sequence. The r-erbA alpha-2 protein binds a DNA fragment containing a putative T3-responsive sequence from the rat GH gene. However, the r-erbA alpha-2 protein product does not bind T3. RNA isolated from rat GH3 cells and various rat tissues contains at least three mRNAs hybridizing to c-erbA alpha probes. A predominant 2.6 kilobase mRNA hybridizes specifically to r-erbA alpha-2, while a 5.0 kb mRNA hybridizes to r erbA alpha-1-specific cDNA probes. The r-erbA alpha-1-related 5.0 kb mRNA is down regulated by T3 treatment in GH3 cells as has previously been described for the 2.6 kb mRNA. The r-erbA alpha-2 mRNA is most abundant in brain, whereas the r erbA alpha-1 mRNA is found in highest concentration in brown fat and skeletal muscle. r-erbA alpha-1 mRNA, unlike r-erbA alpha-2 mRNA, is undetectable in testis. Southern analyses suggest that the r-erbA alpha-1 and r-erbA alpha-2 mRNAs are derived from a single gene transcript. PMID- 2903437 TI - Influenza virus-susceptible mice carry Mx genes with a large deletion or a nonsense mutation. AB - The interferon-regulated mouse Mx gene encodes the 72-kilodalton nuclear Mx protein that selectively inhibits influenza virus replication. Mice carrying Mx+ alleles synthesize Mx protein and resist influenza virus infection, whereas mice homozygous for Mx- alleles fail to synthesize Mx protein and, as a consequence, are influenza virus susceptible. Southern blot analysis allowed us to define the following three distinct Mx restriction fragment length polymorphism (RFLP) types among classical inbred strains: RFLP type 1 in the Mx+ strains A2G and SL/NiA, RFLP type 2 in BALB/c and 33 other Mx- strains, and RFLP type 3 in CBA/J and 2 other Mx- strains. cDNA clones of Mx mRNAs from BALB/c and CBA/J cells were isolated, and their sequences were compared with that of the wild-type Mx mRNA of strain A2G. Mx mRNA of BALB/c mice has 424 nucleotides absent from the coding region, resulting in a frame shift and premature termination of Mx protein. The missing sequences correspond exactly to Mx exons 9 through 11. These three exons, together with some flanking intron sequences, are deleted from the genomes of all Mx RFLP type 2 strains. The Mx- phenotype of the Mx RFLP type 3 strain CBA/J is due to a point mutation that converts the lysine codon in position 389 to a termination codon. Mx RFLP type 3 strains have an extra HindIII site which maps to an intron and thus probably does not affect the coding capacity of Mx mRNA. We further show that the Mx mRNA levels in interferon-treated BALB/c and CBA/J cells are about 15-fold lower than in similarly treated Mx+ cells. This is probably due to decreased metabolic stabilities of the mutant mRNAs. PMID- 2903439 TI - c-erbA protooncogenes mediate thyroid hormone-dependent and independent regulation of the rat growth hormone and prolactin genes. AB - Regulation of gene expression by the thyroid hormones is thought to be mediated by a nuclear-associated receptor found in a wide variety of cells and tissues. Cellular homologues of the avian erythroblastosis virus oncogene, v-erbA, encode proteins which bind thyroid hormone with similar affinities as thyroid hormone receptors. However, it has not been shown that any of the c-erbA proteins can function as receptor and modulate thyroid hormone responsive genes. In this study, using transient expression of chimeric reporter constructs, we document that the chick fibroblast c-erbA-alpha and the human placental c-erbA-beta modulate cis-acting regulatory sequences of two thyroid hormone responsive genes; rat GH and PRL. From these results we conclude: 1) in a receptor deficient cell line (235-1) both c-erbA subtypes act as hormone-dependent modulators of PRL gene expression and hence function as thyroid hormone receptors, 2) in two different receptor containing cell lines (GH4C1 and GH1), both c-erbA proteins act in a hormone-independent fashion to regulate PRL and GH expression. This suggests that events other than ligand binding can result in formation of a c-erbA protein that modulates transcription of thyroid hormone responsive genes, 3) no qualitative functional differences were detected between alpha- and beta-c-erbA subtypes, and 4) depending on the cell-type, L-T3 acts through its endogenous receptor to stimulate (GH4C1) or suppress (GH1) expression of a chimeric PRL construct. In these cells, c-erbA expression results in the same positive or negative response as the endogenous receptor except that the response occurs in the absence of hormone. These results suggest that the endogenous receptor and the c-erbAs act by augmenting the effect of transcription factors which can positively or negatively control gene expression. PMID- 2903440 TI - Growth hormone-releasing hormone stimulates and somatostatin inhibits the release of a novel protein by cultured rat pituitary cells. AB - We have reported that the secretion of at least 17 distinct peptides [including rat (rGH)] GH by cultured rat pituitary cells was stimulated by GH-releasing hormone and inhibited by somatostatin, when analyzed by two-dimensional polyacrylamide gel electrophoresis. Three of these peptides (no. 23, 24, and 25) were not rGH immunoreactive. In order to determine whether these three peptides are fragments, degradation products or posttranscriptionally modified forms of rGH, rGH and peptide no. 23 were characterized structurally. From partial peptide maps of rGH and peptide no. 23 by V8 protease or chymotrypsin, it appeared that these peptides were not related to each other. By N-terminal microsequencing of two-dimensional polyacrylamide gel electrophoresis purified peptide, we have obtained the sequence of 24 N-terminal amino acid residues of peptide no. 23. This sequence has no significant homology with rGH or any other reported protein sequence. Antiserum was generated against a synthetic oligopeptide corresponding to amino acid residues 3-24 of peptide no. 23. The antiserum cross-reacted with peptides no. 23, 24, and 25 upon Western blot analysis. These results indicate that peptide no. 23 has a novel structure unrelated to other pituitary hormones. Since its secretion is influenced by GH-releasing hormone and somatostatin, peptide no. 23 may represent a previously unrecognized structurally unique growth factor. PMID- 2903441 TI - Differences in antibody recognition of the triiodothyronine nuclear receptor and c-erbA products. AB - The in vitro translated products of several c-erbA cDNAs have recently been shown to bind thyroid hormones with high affinity and have been termed thyroid hormone receptors. We have used a panel of five erbA-related antibodies to probe the relationship between c-erbA translated products and thyroid hormone receptors, as conventionally measured by 125I-T3 labeling of nuclear extracts. All five antibodies immunoprecipitated the chick c-erbA translated products, but only one of them recognized chick liver and brain T3 receptor, as judged by acceleration of sedimentation through sucrose gradients. None of the antibodies reacted with rat liver and brain or human liver T3 receptors, although one antibody did immunoprecipitate a human c-erbA translated product. We conclude that the T3 receptor, as conventionally measured from these sources, is related but not identical to recently cloned c-erbA sequences. PMID- 2903442 TI - The molecular nature of spontaneous and chemically induced mutations in the hypoxanthine-guanine phosphoribosyl transferase gene in rat liver epithelial cells. AB - The molecular nature of mutations in 6-thioguanine-resistant hypoxanthine/guanine phosphoribosyl transferase (HGPRT)-deficient clones of an adult rat liver (ARL) epithelial cell line mutated by benzo[a]pyrene or aflatoxin B1 was studied. DNA from these clones or spontaneous HGPRT-deficient mutants was subjected to Southern blotting using an HGPRT probe following DNA digestion with the restriction enzymes BamH1, EcoR1, HindIII or XbaI. With either the chemically induced or spontaneous mutants, no difference in restriction fragment pattern was observed between any of the mutants and their wild-type parent. However, differences were found between two lines ARL 6 and ARL 14 and the lines ARL 18, ARL 19 and DNA from Fischer rat hepatocytes. Although the variants did not display loss of HGPRT activity. It is suggested that deletion or loss of a pseudogene sequence could be the basis for the alterations in restriction fragment patterns. PMID- 2903443 TI - Detection of base mutations in genomic DNA using denaturing gradient gel electrophoresis (DGGE) followed by transfer and hybridization with gene-specific probes. AB - It has been shown that minor differences, such as single-base-pair substitutions between otherwise identical DNA fragments can result in altered melting behavior detectable by denaturing gradient gel electrophoresis (DGGE). Sequence variations in only a small DNA region within one locus can be detected using the previously described procedures. We have developed a method for the efficient Southern transfer of genomic DNA fragments from the denaturing gradient gels in order to be able to analyze larger regions in several loci for variation. The gels were made using polyacrylamide containing 2% low-geling-temperature agarose (LGT). The polyacrylamide gel (PAG) was crosslinked with a reversible crosslinker, and after electrophoresis the crosslinks were cleaved, the structure of the gel being maintained by the agarose. After this treatment of the denaturing gels, more than 90% of the DNA fragments could be transferred to nylon membranes by alkaline transfer, while electroblotting transferred only 10% of the DNA. Hybridization with gene-specific probes was then performed. We have used this technique to identify an RFLP in the COL1A2 gene in a human genomic DNA sample. The transfer technique described should make the use of DGGE more widely applicable since the genomic DNA fragments separated on one gel can be screened with several different probes, both cDNA and genomic probes. PMID- 2903444 TI - Nucleotide sequence analysis of an Entamoeba histolytica ferredoxin gene. AB - A cDNA clone (subclone B) previously isolated from the human parasite Entamoeba histolytica was characterized. DNA sequence analysis of subclone B identified the DNA as that encoding apoferredoxin. E. histolytica ferredoxin cDNA contains unusually short 5' and 3' noncoding regions of 9 and 25 nucleotides, respectively. A genomic ferredoxin clone was isolated from E. histolytica DNA, and comparison of genomic and cDNA sequences revealed that the ferredoxin gene is unspliced. The deduced amino acid sequence of E. histolytica ferredoxin resembles clostridial type of ferredoxins, and shows an arrangement of cysteines characteristic for the coordination of 2[4Fe-4S] centres. Of interest is the absence of an aromatic amino acid in the N-terminal region of the protein, a feature which is conserved in clostridial ferredoxins. Southern blot analysis of three different E. histolytica strains (200:NIH, Rahman and HM-1:IMSS) demonstrated the presence of a family of at least two ferredoxin genes. One of these genes is marked by restriction length polymorphisms in different strains of E. histolytica. PMID- 2903445 TI - Structure of a Plasmodium falciparum gene that encodes a glutamic acid-rich protein (GARP). PMID- 2903446 TI - Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer. AB - Amplification of the neu proto-oncogene in breast cancer has been reported to correlate with the presence of lymph-node metastases and with a poor prognosis. We describe a method for the immunohistochemical detection of overexpression of neu protein on formalin-fixed paraffin-embedded tissue, with the use of two different monoclonal antibodies. In a group of tumors with a known neu-gene copy number, intense membrane staining of tumor cells was present in all tumors with neu-gene amplification. Of 189 tumors from patients with Stage II breast cancer, 27 (14 percent) had neu-membrane staining. Neu overexpression was associated with larger tumor size (P = 0.006) but not with lymph-node involvement. Neu-protein expression in lymph-node metastases was the same as its expression in primary tumors. Among the patients with neu overexpression (median follow-up, 37 months), disease-free survival was not significantly shorter; overall survival was reduced significantly in these patients (P = 0.042), but this reduction did not remain significant after adjustment for tumor size. Of 45 ductal carcinomas in situ, 19 (42 percent) had neu-membrane staining. These 19 were all of the large-cell, comedo growth type. None of 16 ductal carcinomas in situ of small-cell, papillary, or cribriform growth type had neu overexpression. We conclude that neu overexpression may be an early step in the development of a distinct histologic type of carcinoma of the breast, but we could find no association of overexpression with lymph-node status or tumor recurrence. PMID- 2903447 TI - Splitting schizophrenia. PMID- 2903448 TI - Restoration of excitation-contraction coupling and slow calcium current in dysgenic muscle by dihydropyridine receptor complementary DNA. AB - Microinjection of an expression plasmid that carries complementary DNA encoding the receptor for dihydropyridine calcium channel blockers of skeletal muscle restores both excitation-contraction coupling and slow calcium current in cultured skeletal muscle cells from mice with muscular dysgenesis. This suggests that the dihydropyridine receptor in the transverse tubule membrane of skeletal muscle functions both as the voltage sensor for excitation-contraction coupling and as the slow calcium channel. PMID- 2903449 TI - Localization of a susceptibility locus for schizophrenia on chromosome 5. AB - Schizophrenia is a common disorder with a life time prevalence of approximately 1 per cent. The illness often develops in young adults, who were previously normal, and is characterized by a constellation of symptoms including hallucinations and delusions (psychotic symptoms) and symptoms such as severely inappropriate emotional responses, a disorder of thinking and concentration, erratic behaviour as well as social and occupational deterioration. A considerable proportion of the variance in the liability to develop schizophrenia may be genetic, but segregation analysis, to establish a mode of transmission, has not produced a consistent result. One of these studies was carried out in Iceland and made use of the large family size and extensive geneaological information present in that country. Here we demonstrate genetic linkage of two DNA polymorphisms on the long arm of human chromosome 5 to schizophrenia in seven British and Icelandic families with multiple affected members. The results indicate the existence of a gene locus with a dominant schizophrenia-susceptibility allele. Inheritance of the allele in the families studied suggests that it may also predispose to psychiatric conditions such as schizophrenia spectrum disorders and a variety of other disorders. This report provides the first strong evidence for the involvement of a single gene in the causation of schizophrenia. PMID- 2903450 TI - Evidence against linkage of schizophrenia to markers on chromosome 5 in a northern Swedish pedigree. AB - Schizophrenia is a severe mental illness with a typically chronic course affecting nearly 1% of the human population. It is generally accepted that genetic factors have an important pathogenic role in a substantial portion of schizophrenia cases; however, despite decades of family studies, there is no agreed-upon mode of inheritance. The discovery of genetic aetiologic factors and resolution of the inheritance pattern(s) will undoubtably emerge from genetic linkage studies. With these objectives in mind, we undertook a linkage project, starting in 1985, in a previously well-documented kindred from north Sweden. Multipoint linkage analyses were used to screen the proximal long arm of chromosome 5 using restriction fragment length polymorphism (RFLP) markers at five loci and the distal long arm using RFLPs at two loci, one of which was the locus for the glucocorticoid receptor. We found strong evidence against linkage between schizophrenia and the seven loci. These results, together with the positive evidence for linkage of schizophrenia with markers in the proximal long arm of chromosome 5 lead us to conclude that the genetic factors underlying schizophrenia are heterogeneous. PMID- 2903452 TI - Management of the agitated patient. A pharmacological update. PMID- 2903453 TI - [Clenbuterol: 'redistribution agent']. PMID- 2903451 TI - Dopamine neurochemical profile of atypical antipsychotics resembles that of D-1 antagonists. AB - The release and metabolism of dopamine in the mouse caudate-putamen were determined after the oral administration of antipsychotic drugs at doses equal to or sixfold greater than the ED50 dose for their inhibition of apomorphine-induced climbing. Dopamine release was equated with concentrations of 3-methoxytyramine (3-MT) and metabolism was equated with concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. Like the D-1 antagonists SCH 23390 and SKF 83566, most antipsychotic agents with an atypical preclinical profile suggestive of low extrapyramidal symptomatology (CGS 10746B, flumezapine, CL 77328, rimcazole, clozapine, RMI 81582, and fluperlapine) never increased dopamine release and produced variable increases in dopamine metabolism. Other atypical antipsychotics (thioridazine, mesoridazine, melperone) increased dopamine release at only one dose tested but increased dopamine metabolism at most doses. Antipsychotic agents associated with extrapyramidal side effects (setoperone, perlapine, haloperidol, chlorpromazine, and metoclopramide) increased dopamine release and metabolism at almost every dose tested. Thus, atypical antipsychotics increase the metabolism but not release of dopamine at behaviorally effective doses. The resemblance of these minimal effects on dopamine release to those obtained with D-1 antagonists that also have an atypical preclinical profile suggests that a mechanism related to D-1 receptor antagonism may contribute to the action of atypical antipsychotics. PMID- 2903454 TI - [Glafenine: more cons than pros?]. PMID- 2903455 TI - [Once more on benzodiazepines: too much, too long and too strong?]. PMID- 2903456 TI - [Lasting neurological damage with therapeutic plasma lithium levels]. PMID- 2903457 TI - [Sharp decrease in the frequency of orchidopexy in Walcheren]. PMID- 2903458 TI - An update: lab for the silent service. PMID- 2903459 TI - Multiple forms of beta-amyloid peptide precursor RNAs in a single cell type. AB - The longest open reading frames (ORFs) of three different cDNAs ([10, 12, 18, 26], and this report) contain the exact 42 amino acid (aa) sequence of the beta amyloid peptide (BAP) which is selectively deposited in Alzheimer's diseased (AD) brains. Each of the three cDNAs for the putative amyloid peptide precursor (APP) has been cloned from a different cell type. Using an HL 60 library, we have cloned two of these three APP cDNAs from a single cell type. The sequences of the HL 60 cDNAs are identical to the APP 751 and to the APP 770 forms of APP cDNAs. Northern blots show that oligonucleotide probes drawn from unique regions of the APP 751 and APP 770 cDNAs both hybridize to 4.0 Kilobase (Kb) and to 1.6 Kb APP RNAs from HL 60 cells. In human adult brain, an oligonucleotide probe drawn from the unique region of the APP 751 cDNA hybridizes to a 3.5 Kb APP RNA. However, a DNA probe drawn from the BAP region, which is common to the 695, 751, and 770 forms of APP cDNAs, hybridizes to 3.5, 3.2 and 1.6 Kb APP RNAs. Taken together, these results show that at least two forms of APP RNAs can exist within a single cell type and that the diversity of possible APP RNAs and complexity of their expression may have been underestimated. Thus, in addition to identifying the cells which produce BAP, a new challenge consists of determining which form of forms of APP RNAs and hence APP proteins are associated with BAP deposition in AD and Down syndrome (DS). PMID- 2903460 TI - Corticosterone decreases 3H-glutamate binding in rat hippocampal formation. AB - The effect of in vivo corticosterone manipulation on binding sites for the excitatory neurotransmitter glutamate was determined using radioligand binding to rat brain cryostat sections and crude synaptic membranes. 3H-glutamate binding to regions of the dorsal hippocampal formation was significantly decreased in adrenalectomized animals following 5-10 days of corticosterone treatment. Corticosterone did not alter 3H-glutamate binding in several other brain regions. The loss in 3H-glutamate binding appeared to be due to a decrease in the maximal number of binding sites, with little change in binding affinity. Both chloride dependent and chloride-independent 3H-glutamate binding sites were decreased by corticosterone treatment. results indicate that corticosterone can selectively alter binding sites for excitatory amino acids in hippocampal tissue. PMID- 2903461 TI - Effects of systemic and intracerebroventricular cysteamine on dexamethasone induced suppression of corticosterone levels in the rat. AB - To investigate whether somatostatin systems plays a significant role in the regulation of the hypothalamic-pituitary-adrenal axis, the effects of cysteamine, a drug which reduces somatostatin levels, on the dexamethasone-induced suppression of plasma corticosterone levels were examined in the rat. Male Long Evans rats were handled daily for 1 week prior to receiving a standard dexamethasone suppression test. On the 1st day, rats received a 9.00 a.m. saline injection and blood samples were taken from the tail at 1.00 p.m. On the 2nd day, rats received dexamethasone or saline at 9.00 a.m. and a second blood sample was taken at 1.00 p.m. Experimental groups were pretreated with systemic injections of cysteamine, 5 min or 14 h, prior to receiving dexamethasone. Additional groups, previously implanted with guide cannulae, were given an infusion of cysteamine or saline into the lateral ventricle 14 h prior to dexamethasone. Circulating corticosterone levels were determined by radioimmunoassay. Rats were sacrificed immediately following each experiment and the hypothalamus dissected and assayed for levels of somatostatin immunoreactivity. The results of the first experiment showed that dexamethasone (10 micrograms/kg) alone reduced plasma corticosterone levels from control values (174 +/- 36 ng/ml) to undetectable levels (less than 25 ng/ml). Pretreatment with cysteamine 5 min prior to dexamethasone, while having no significant effect on basal corticosterone levels, completely blocked the dexamethasone-induced suppression of corticosterone levels. Similar observations were obtained with rats pretreated with cysteamine 14 h prior to dexamethasone. In contrast, intracerebroventricular cysteamine pretreatment did not block the dexamethasone-induced suppression of corticosterone levels. These results add further evidence in support of an involvement of somatostatin systems in the regulation of the hypothalamic pituitary-adrenal axis. PMID- 2903462 TI - Changes in tuberoinfundibular dopaminergic neuron activity during the rat estrous cycle in relation to the prolactin surge: alteration by a mammary carcinogen. AB - An attempt was made to correlate the physiological or the dimethylbenz(a)anthracene (DMBA)-enhanced serum prolactin (PRL) surge, which occurs in the afternoon of proestrus in female Sprague-Dawley (SD) rats, with physiological or pathological changes in two biochemical estimates of the tuberoinfundibular dopaminergic (TIDA) neuron activity. Dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) concentrations as well as tyrosine hydroxylase (TH) activity were measured in the median eminence (ME) of control or DMBA pretreated SD rats throughout the estrous cycle in relation to PRL secretion. In both groups of females, while the DA content was fairly constant, the DOPAC content and TH activity in the ME fluctuated markedly throughout the estrous cycle. Thus, in control animals, the DOPAC content, DOPAC/DA ratio and TH activity which were stable on the days of diestrus and morning of proestrus were markedly decreased at noon and early afternoon when serum PRL levels began to rise. Later in the afternoon of proestrus, when serum PRL levels were maximal, there was a marked but transient increase in the DOPAC content and DOPAC/DA ratio as well as a brief surge in TH activity. In the evening of the same day, when serum PRL returned to basal levels, the DOPAC content, DOPAC/DA ratio and TH activity were low. Finally on estrus morning, the DOPAC content, DOPAC/DA ratio and TH activity increased again to reach the diestrus levels. In DMBA-pretreated females, similar fluctuations in TIDA neuronal activity occurred during the estrous cycle, but the dynamics of these changes was altered: the DOPAC/DA ratio and TH activity first showed a marked increase in the morning of proestrus day, before decreasing dramatically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903463 TI - Effect of minaprine on synaptic transmission in the neocortex of the rat in vivo. AB - The effects of minaprine and/or excitatory amino acid antagonists on transcallosal responses were examined in urethane-anesthetized rats. The transcallosal response was recorded from the surface of the anterior neocortex, following electrical stimulation of the contralateral corpus callosum. The transcallosal response consisted of a biphasic positive-negative waveform. Intravenously-administered minaprine increased the amplitude of the positive- and negative-waves, in a dose-dependent manner. Intracortical injection of (+/-)-2 amino-5-phosphonovalerate (APV) and gamma-D-glutamylglycine (DGG) reduced the amplitude of the negative-wave, with no effects on the amplitude of the positive wave. L-Glutamate diethylester (GDEE) had no effect on the transcallosal response. The minaprine-induced increase in the amplitude of the negative-wave was completely antagonized by simultaneous intracortical injections of APV and DGG which, per se, did not affect that transcallosal response. In contrast, APV and DGG had no effect on the increase in the amplitude of the positive-wave induced by minaprine. The enhancing effect of minaprine on the transcallosal response remained unaltered in case of an intracortical injection of GDEE. These findings indicate that the negative-wave of the transcallosal response may be related to receptors for excitatory amino acids. The possibility that the pharmacological action of minaprine on synaptic transmission in the neocortex may be linked to the excitatory amino acid receptors warrants further attention. PMID- 2903464 TI - Sardinian multiple sclerosis is associated with HLA-DR4: a serologic and molecular analysis. AB - HLA haplotypes in 45 unrelated Sardinian multiple sclerosis patients and in six multiplex families were defined, using both serologic and restriction fragment length polymorphism (RFLP) analysis. In unrelated MS patients, we found an association with HLA-DR4 (p less than 0.01, relative risk = 2.5) and DQw3 (p less than 0.04, relative risk = 2.2). Using a beta-DR cDNA probe, we observed no variation of the DR4 RFLP profile in sporadic or related MS patients compared with DR4-specific pattern in controls. Using a beta-DQ cDNA probe, we identified two DQw3 patterns (DQw3.1 and DQw3.2) with similar frequency in patients and in controls. No specific RFLPs were observed in association with different disease courses. The frequency of haplotype sharing in affected members of multiplex families was not different from that expected by chance. This study shows that Sardinian MS patients carry predominantly the HLA-DR4 allele, in contrast to the DR2 prevalence reported in Caucasian populations. The lack of association with HLA haplotypes in affected members of multiplex families may indicate that genetic factors outside the HLA system play a substantial role in families with MS. PMID- 2903465 TI - One-year prevalence of lower extremity injuries among active duty military soldiers. PMID- 2903466 TI - [Clinical experimentation with a new antihistaminic molecule in allergic conjunctivitis]. AB - Current pathogenetic and symptomatological knowledge of allergic conjunctivitis and its treatment with a recently synthesised antihistaminic molecule, Astemizole, is reported. PMID- 2903467 TI - Pharmacological evidence that somatostatin activates the m-current in hippocampal pyramidal neurons. AB - In the in vitro hippocampal slice somatostatin has been shown to cause a direct hyperpolarization of CA 1 pyramidal neurons by increasing a potassium conductance which is resistant to blockade by tetraethylammonium 4-aminopyridine, or cesium ions. Results reported here demonstrate that this somatostatin-induced hyperpolarization is blocked by 1 mM barium and 5 x 10(-5) M carbachol, with the action of carbachol being reversed by atropine. Barium and carbachol both inactivate the m-current and these results suggest that somatostatin may exert its hyperpolarizing action on CA1 pyramidal cells by activation of the m-current. PMID- 2903468 TI - Effect of carbamazepine on stimulus-evoked Ca2+ fluxes in rat hippocampal slices and its interaction with A1-adenosine receptors. AB - In rat hippocampal slices superfused with a medium lacking Mg2+ ions, CA1 neurons generated burst discharges which were sensitive to blockade by 2-amino-5 phosphonovaleric acid (APV) and antagonized by 20-50 microM carbamazepine (CBZ). Decreases of [Ca2+]o (delta Ca), evoked by repetitive synaptic activation, were reduced in the presence of CBZ by 20-50%, associated with a reduced membrane depolarization. CBZ also abolished an APV-sensitive increase of delta Ca in the synaptic area elicited by theophylline. CBZ inhibited binding of the A1-adenosine receptor antagonist, [3H]8-cyclopentyl-1,3-dipropylxanthine [( 3H]DPCPX), in a dose-dependent manner. The displacement curve was shifted to the left in the presence of guanine nucleotide, suggesting that CBZ acts as an antagonist at A1 receptors. It is concluded that CBZ exerts its electrophysiological actions in the hippocampus at a site beyond the ligand recognition moiety. PMID- 2903469 TI - Non-competitive antagonists of N-methyl-D-aspartate receptors protect cortical and hippocampal cell cultures against glutamate neurotoxicity. AB - Brief exposure of cortical or hippocampal cell cultures to glutamate (500 microM) resulted in a progressive neuronal necrosis which is maximal 18-24 h later. Pretreatment of the cultures by a phencyclidine derivative: thienylphencyclidine (TCP), or the TCP precursor: GK86, or MK801 protected against glutamate toxicity. Non-competitive antagonists of N-methyl-D-aspartate receptors appear as potent tools for the in vitro protection of neuronal cells against excitatory amino acid toxicity. PMID- 2903470 TI - Release of proteins during long-term potentiation in the hippocampus of the anaesthetized rat. AB - Using a push-pull device, the release of endogenous proteins in the extracellular space was investigated in the CA1 region of the hippocampus of anaesthetized rats. With low-frequency stimulation of the Schaffer collaterals, there was a relatively stable release of 5 proteins (64, 54, 48, 45 and 16 kDa). A train of high-frequency stimulation produced a long-lasting enhancement of the negative field EPSP and a delayed (90-120 min) enhancement of the release of these proteins. An additional 19 kDa protein was present only 90 min after the train. These observations raise the possibility that release of proteins might be involved in the maintenance of LTP. PMID- 2903472 TI - Endogenous GABA released into the fourth ventricle of the rat brain in vivo is enhanced by noxious stimuli. AB - In vivo release of endogenous gamma-aminobutyric acid (GABA) and glutamic acid into the 4th ventricle of the rat brain in response to noxious stimuli was examined. Both these compounds were dansylated and the concentrations determined, using high-performance liquid chromatography (HPLC) combined with an UV detector. Following noxious stimuli (subcutaneous injection of diluted formalin into the hind-paw or noxious pinch of the hind-paws), there was a remarkable release of GABA, but not of glutamic acid. Basal on our heretofore obtained data that bicuculline methiodide, a GABAA antagonist, produces a potent analgesia in mice, the present results suggest that the GABAergic system in the brain stem may promote nociceptive transmission in rats. PMID- 2903471 TI - Blockade of excitatory synaptic transmission by 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX) in the hippocampus in vitro. AB - Superfusion of hippocampal slices with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 2-5 microM) reversibly blocked the Schaffer collateral and mossy fibre excitatory postsynaptic potential (EPSP), while sparing the fast and slow gamma aminobutyric acid (GABA)-mediated inhibition. Membrane potential, input resistance and spike accommodation were not altered. Inward currents induced by quisqualate were reduced to a greater extent by CNQX than those induced by kainate or N-methyl-D-aspartate. We suggest that CNQX may be a useful antagonist to study excitatory amino acid-mediated synaptic transmission. PMID- 2903473 TI - Non-competitive inhibition of GABA currents by phenothiazines in cultured chick spinal cord and rat hippocampal neurons. AB - The gamma-aminobutyric acid (GABA) inhibiting properties of several classes of antipsychotic medications were studied using gigaseal whole-cell voltage-clamp techniques in cultured chick spinal cord and rat hippocampal neurons. At doses above 1 microM trifluoperazine, chlorpromazine and thioridazine blocked GABA currents in a non-competitive fashion decreasing the maximal transmitter response without altering the half-maximal effective concentration. In contrast, haloperidol was ineffective against GABA at concentrations up to 100 microM. Among the agents studied trifluoperazine was the most potent GABA inhibitor with half maximal effect at 12 microM. Trifluoperazine (100 microM) also inhibited glycine-gated chloride currents in spinal cord neurons to an extent comparable to GABA (85 +/- 6% inhibition) but reduced glutamate currents by less than 35% in either spinal cord or hippocampal neurons. PMID- 2903474 TI - Thyrotropin releasing hormone (TRH) modified excitability of spinal cord dorsal horn cells. AB - Thyrotropin releasing hormone (TRH) has been identified recently in fibers and cell bodies in the dorsal horn of the spinal cord, but its function in the dorsal horn is not known. The present study investigated the effects of TRH applied by iontophoresis on the excitability of dorsal horn cells that were responsive to mechanical stimulation of the ipsilateral hindlimb. TRH facilitated glutamate induced firing of these cells without directly driving the cells in the absence of glutamate. These results suggest that TRH may modulate transmission of somatosensory information in the spinal cord. PMID- 2903475 TI - Administration of GM1 ganglioside eliminates neuroleptic-induced sensorimotor deficits in MPTP-treated mice. AB - Injection of a low dose of haloperidol, that has no obvious behavioral effects in normal mice, produces akinesia, catalepsy, and sensory neglect in MPTP-treated mice. GM1 ganglioside treatment eliminates all of these behavioral impairments and also partially restores striatal dopamine content. These observations suggest that the MPTP-treated mouse may be a valuable model for studying mechanisms underlying parkinsonism and that administration of GM1 ganglioside may be an effective therapy. PMID- 2903476 TI - Ketamine blocks an NMDA receptor-mediated component of synaptic transmission in rat hippocampus in a voltage-dependent manner. AB - We have examined the voltage dependence of the effects of ketamine on synaptic currents in hippocampal CA1 neurons in vitro under conditions where there is a large N-methyl-D-aspartate (NMDA) receptor mediated component of the response. Ketamine reduced inward currents to a greater extent than outward currents of a corresponding size. D-2-Amino-5-phosphonovalerate (APV) substantially reduced the residual outward currents recorded in ketamine, but had only a small effect on the residual inward ones. It is concluded that in this system the action of ketamine in blocking synaptically evoked NMDA receptor-mediated currents shows some voltage dependence. PMID- 2903477 TI - [Histological study of splenic colonies at different times following the transplantation of hematopoietic cells from embryonic liver]. AB - Histological analysis was carried out on the hemopoietic spleen colonies within 7 and 11 days after transplantation of the embryonic liver cells. Large superficial colonies were always present and were, predominantly, erythroid and mixed. Small superficial colonies consisted of undifferentiated cells and, unlike large colonies, appeared on the 11th day only. In the spleen thickness erythroid colonies predominated. The possibility of formation of small superficial 11 day colonies at the expense of pre-CFU-S is discussed. PMID- 2903478 TI - [Biochemical changes in the liver of the rat after ligation of the common bile duct]. PMID- 2903479 TI - Monitoring serum aminoglycoside concentrations in children with amphotericin B nephrotoxicity. AB - We prospectively studied the effect of amphotericin B therapy on aminoglycoside clearance in 20 consecutive children during the remission-induction phase of chemotherapy for acute myelocytic leukemia. Increases (greater than 50%) in the half-life for aminoglycoside excretion were not associated with antileukemic or aminoglycoside therapy alone but occurred in 12 of 17 children when amphotericin B was added to the antimicrobial regimen. Seven children had impaired aminoglycoside clearance without increases (greater than 50%) in serum creatinine; hence the resulting adjustments in aminoglycoside dosage would not have been made had we relied solely on serial measurements of serum creatinine. Evidence for increased excretion of the renal enzymes N-acetyl-beta-D glucosaminidase and alanine aminopeptidase during amphotericin B therapy suggested that damage to proximal tubular cells may contribute to the renal impairment that has been associated with this drug. Our findings underscore the value of monitoring serum aminoglycoside concentrations in children being treated with amphotericin B. PMID- 2903480 TI - Surfactant replacement therapy for severe neonatal respiratory distress syndrome: an international randomized clinical trial. Collaborative European Multicenter Study Group. AB - In a randomized multicenter trial, involving the collaboration of eight European neonatal intensive care units, the efficacy of replacement therapy with a new surfactant preparation (Curosurf) was tested in 146 patients with severe neonatal respiratory distress syndrome. Criteria for entry included birth weight 700 to 2,000 g, age when treated two to 15 hours, and requirement of artificial ventilation with FiO2 greater than or equal to 0.6. The babies were treated with a single large dose of surfactant (200 mg/kg) at a median age of nine hours (range two to 15 hours). Average FiO2 before treatment was the same (0.80) for both surfactant-treated patients and control patients. Babies receiving surfactant showed, within five minutes, a dramatic improvement of oxygenation as reflected by a nearly threefold increase of the PaO2/FiO2 ratio. Six hours after randomization, the PaO2/FiO2 ratio still showed a 98% improvement in surfactant treated patients compared with controls (P less than .001), and statistically significant differences in favor of the treated babies persisted until 48 hours after randomization, when surviving control infants began to recover. Treatment with surfactant decreased neonatal (less than or equal to 28 days) mortality from 51% to 31% (P less than .05). Compared with control babies, the surfactant treated group also had a decreased incidence of pulmonary interstitial emphysema (23% v 39%; P less than .05) and pneumothorax (18% v 35%; P less than .05). The percentage of survivors without bronchopulmonary dysplasia in the treated group was more than twice that of the control group (55% v 26%; P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903481 TI - Persistent human immunodeficiency virus type 1 antigenemia in children correlates with disease progression. AB - In a longitudinal study, human immunodeficiency virus type 1 (HIV-1) antigen (HIV Ag) was measured in serum specimens from 54 children with HIV-1 infection followed for a median duration of 17 months. The persistent detection of free HIV Ag in a group of 25 children was associated with clinical deterioration in 22 (88%) and a mortality of 52%, whereas the persistent nondetection of free HIV-Ag in a group of 18 children was associated with clinical deterioration in five (28%) and a mortality of 11% during the period of observation. Nine children had transient HIV-1 antigenemia and two children converted from HIV-Ag negative to positive during the study. Free HIV-Ag levels varied inversely with antibody reactivity to viral core proteins p24 and p17 determined by Western immunoblot, suggesting either the formation of immune complexes or a balance between viral expression and the host immune response. Five mother-infant pairs were studied for HIV-Ag expression in the perinatal period. In three of these pairs, both mother and infant were HIV-Ag negative, in one pair the mother had high levels of HIV-Ag and the infant was HIV-Ag negative. In the remaining mother-infant pair, the neonate became HIV-Ag positive but the mother was HIV-Ag negative prepartum and postpartum. These data suggest that HIV-Ag probably does not cross the placenta and that the detection of free HIV-Ag in the offspring of a HIV-1 infected mother most likely indicates viral infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903483 TI - Isolation and mapping of a polymorphic DNA sequence (pMCT96.1 and pMCT96.2) on chromosome 9q [D9S14]. PMID- 2903482 TI - Random oligonucleotide mutagenesis: application to a large protein coding sequence of a major histocompatibility complex class I gene, H-2DP. AB - We have used random oligonucleotide mutagenesis (or saturation mutagenesis) to create a library of point mutations in the alpha 1 protein domain of a Major Histocompatibility Complex (MHC) molecule. This protein domain is critical for T cell and B cell recognition. We altered the MHC class I H-2DP gene sequence such that synthetic mutant alpha 1 exons (270 bp of coding sequence), which contain mutations identified by sequence analysis, can replace the wild type alpha 1 exon. The synthetic exons were constructed from twelve overlapping oligonucleotides which contained an average of 1.3 random point mutations per intact exon. DNA sequence analysis of mutant alpha 1 exons has shown a point mutant distribution that fits a Poisson distribution, and thus emphasizes the utility of this mutagenesis technique to "scan" a large protein sequence for important mutations. We report our use of saturation mutagenesis to scan an entire exon of the H-2DP gene, a cassette strategy to replace the wild type alpha 1 exon with individual mutant alpha 1 exons, and analysis of mutant molecules expressed on the surface of transfected mouse L cells. PMID- 2903484 TI - Isolation and mapping of a polymorphic DNA sequence (pMCT15) on chromosome 21 [D21S113]. PMID- 2903485 TI - Isolation and mapping of a polymorphic DNA sequence (pRMR6) on chromosome 20 [D20S20]. PMID- 2903486 TI - Isolation and mapping of a polymorphic DNA sequence (pYNZ94) on chromosome 17 [D17S80]. PMID- 2903487 TI - Isolation and mapping of a polymorphic DNA sequence (pEKMDA2-I) on chromosome 16 [D16S83]. PMID- 2903489 TI - Isolation and mapping of a polymorphic DNA sequence (pTHH28) on chromosome 7p [D7S371]. PMID- 2903488 TI - Isolation and mapping of a polymorphic DNA sequence (pKKA12) on chromosome 7 [D7S398]. PMID- 2903490 TI - Isolation and mapping of a polymorphic DNA sequence (pEFD6) chromosome 6 [D6S41]. PMID- 2903491 TI - Isolation and mapping of a polymorphic DNA sequence (pYNZ132) on chromosome 6 [D6S40]. PMID- 2903492 TI - RFLP for TaqI at the human tyrosinase locus. PMID- 2903493 TI - Effect of product form on the microbiological growth support characteristics of turkey meat products. AB - Effects of product form classifications, consisting of intact turkey drumsticks, dark meat trim tissue, and mechanically deboned meat, on microbiological concentrations were evaluated. Samples were inoculated with actively growing cultures of Salmonella and Clostridium perfringens to increase naturally low bacterial populations prior to being placed at 1 C and 10 C for storage evaluations. Growth support potential for all product forms stored at 10 C was extensive, making it difficult to characterize individual product form effects. Results from samples stored at 1 C indicated that emulsion and trim tissue afforded the greatest growth support potential, probably due to the increased nutrient availability and potential protective effects of the environment associated with the increased surface area of these tissues. PMID- 2903494 TI - Neuroinhibition of xylazine induced emesis. AB - Xylazine produces retching and vomiting presumably by activation of the chemoreceptor trigger zone (CTZ). The purpose of this project was to investigate whether neuroinhibition can prevent xylazine vomiting. Inhibitory neurons in the cervical vagus nerve of cats were stimulated with implanted cuff electrodes. Female cats, weighing from 3 to 4 kg, were anaesthetized with pentobarbital for surgical implantation of electrodes. After full recovery from surgery, animals were tested in weekly sessions. Stimulation was via a pulse generator connected to photon coupled linear isolator supplying constant current. Videotape was used to record observations. The range of effective stimulation was 1-10 ma, 4-100 Hz and 0.3-0.6 msec. Stimulation was initiated thirty sec. after subcutaneous injection of xylazine, 0.66 mg/kg. Stimulation of the inhibitory nerve group of the cervical vagus was effective in preventing vomiting in over 85% of the experimental trials. In addition to preventing emesis during stimulation, the latency of xylazine emesis was increased over control values. Repeated experimental trials of stimulation coupled with xylazine injection could result in the complete absence of emesis. PMID- 2903495 TI - The effects of H1- and H2-receptor blocking agents on postsynaptic potentials recorded from the bull-frog sympathetic ganglion. AB - The effects of H1-blockers (pyrilamine, diphenhydramine and promethazine) and H2 blockers (cimetidine, ranitidine) on the postsynaptic potentials of the bull-frog sympathetic ganglion were studied by means of the sucrose gap method. All the H1 blockers tested, at concentrations of 10(-6)-10(-4) M, depressed the amplitudes of both action and slow postsynaptic potentials in positive and negative directions in a concentration-dependent manner; these drugs had more potent inhibitory effects on postsynaptic potentials. In the case of H2-blockers, action and postsynaptic potentials were slightly depressed as perfusion continued at 10( 4) M. From the present experiments, it was concluded that H1-blockers directly inhibit postsynaptic potentials of the sympathetic ganglions, and that this inhibition may be responsible for various autonomic disturbances attributed to H1 blockers. PMID- 2903496 TI - Inhibition of cyclic AMP production by alpha 2-adrenoceptor stimulation in the guinea-pig spinal cord slices. AB - In spinal cord slices isolated from guinea-pig and preincubated with 3H-adenine, 0.3-30 microM forskolin induced a dose-dependent increase in the content of 3H cAMP, the maximal increase being about 8-fold. The selective alpha 2-adrenergic agonist UK-14,304 (10 microM) reduced both the basal and the forskolin stimulated levels of 3H-cAMP by 18-32%. Dose response curves of the effect of UK-14,304 on cAMP production in the spinal cord slices, stimulated with 3 microM forskolin, showed an IC50 of 37 nM and a maximally inhibitory effect of 27%. A number of other alpha 2-adrenergic agonist (clonidine, guanfacine, B-HT 920 and B-HT 933) also inhibited the forskolin stimulated 3H-cAMP production; clonidine and guanfacine being almost equipotent with UK-14,304, but their maximal inhibitory effects being only about 6-7%. B-HT 920 and B-HT 933 were less potent and their maximal inhibitory effects about 16-21%. The dose response curve of UK-14,304 on inhibition of forskolin stimulated cAMP production was shifted almost 50-fold to the right by 0.3 microM yohimbine. Prazosin (0.3 microM) did not affect the UK 14,304 dose response curve. It is concluded that alpha 2-adrenoceptor stimulation mediates inhibition of cAMP production in the guinea-pig spinal cord. PMID- 2903497 TI - Functional reconstitution of a proton-translocating system responsive to fusicoccin. AB - Crude fusicoccin binding proteins and a partially purified plasma membrane H+ transporting ATPase (EC 3.6.1.34), both solubilized from maize tissues, were simultaneously inserted into liposomes by the freeze-thaw method. ATP-driven intravesicular acidification in the proteoliposomes, measured by the fluorescence quenching of the dye 9-amino-6-chloro-2-methoxyacridine, markedly increased upon addition of fusicoccin to the reconstituted system. This effect could not be observed when binding sites and ATPase preparations were separately reconstituted into the proteoliposomes, thus demonstrating that fusicoccin binding to its receptor is a prerequisite for ATPase stimulation. PMID- 2903498 TI - Numerous transcription initiation sites exist for the maize mitochondrial genes for subunit 9 of the ATP synthase and subunit 3 of cytochrome oxidase. AB - Transcripts for plant mitochondrial genes are frequently present as multiple size classes. In maize, these differences often result from variation in the 5' noncoding region. To determine where transcription initiates, primary (unprocessed) transcripts were specifically labeled in vitro by the capping reaction catalyzed by guanylyltransferase. Direct mapping of transcription initiation sites was accomplished by hybridization of in vitro-capped RNA with the 5' flanking sequences of mitochondrial genes and subsequent digestion with single-strand-specific RNases. The RNase protection experiments identified three transcription initiation sites for subunit 3 of cytochrome oxidase and at least six transcription initiation sites for subunit 9 of ATP synthase. Thus, transcript size heterogeneity is primarily the result of multiple transcription initiation sites for these genes rather than RNA processing. Primer extension analyses of maize mitochondrial RNA were used to precisely establish the sequences at the initiation sites. Comparison of sequences at transcription initiation sites suggests that some homology exists at these sites, although no highly conserved consensus sequence is obvious. PMID- 2903499 TI - Ethylene-regulated expression of a tomato fruit ripening gene encoding a proteinase inhibitor I with a glutamic residue at the reactive site. AB - We report the isolation from tomato (Lycopersicon esculentum) of an ethylene responsive member of the proteinase inhibitor gene family. DNA sequence analysis of a full-length cDNA clone indicates that the ethylene-responsive gene is distantly related to the tomato proteinase inhibitor I gene, having 53% sequence identity. The predicted amino acid sequence reveals 47% and 45% sequence identity with the tomato and potato proteinase inhibitor I polypeptides, respectively. Additionally, the ethylene-responsive inhibitor has evolved a completely different pattern of gene expression and inhibitory specificity than other members of the inhibitor I family. Gel blot hybridization experiments show that, unlike the tomato proteinase inhibitor I gene, it is not induced in wounded leaves. In contrast, it is activated by the plant hormone ethylene in leaves and during fruit ripening. Furthermore, the ethylene-responsive inhibitor exhibits a novel reactive site, having glutamic acid as the P1 residue. This suggests that the ethylene-responsive proteinase inhibitor does not react with chymotrypsin, as does proteinase inhibitor I, but that it reacts with proteolytic enzymes that cleave at glutamic residues, such as the Staphylococcus aureus V8 proteinase, for which no inhibitors are known. Finally, isolation and analysis of a genomic clone reveals that the ethylene-responsive proteinase inhibitor gene is tightly linked to another, yet unidentified, coordinately expressed gene. We discuss these results with regard to the function and evolution of proteinase inhibitor genes in tomato. PMID- 2903501 TI - Conserved upstream sequences of human class II major histocompatibility genes enhance expression of class II genes in wild-type but not mutant B-cell lines. AB - Class II major histocompatibility genes contain a conserved upstream sequence (CUS) that is important in the expression of these genes. This region has been divided into two major elements, the X box and the Y box. The ability of these elements to mediate transcription of a heterologous promoter was assayed upon transfection into a B-cell line (Raji), a class II-specific trans-acting factor deficient B-cell line (RJ2.2.5 cells), and a T-cell line (Jurkat). The results showed that the X box element was responsible for directing tissue-specific expression when Raji cells were compared to Jurkat cells. The X box could not direct expression of the heterologous promoter in the trans-acting factor deficient cell line, indicating that the X box is an ultimate target of the missing or defective factor in the RJ2.2.5 cell line. The Y box directed an equal but extremely low level of transcription in this system in both the mutant and wild-type B-cell lines, suggesting that this element is not involved in B-cell expression or as a target of the mutant factor. PMID- 2903500 TI - neu protooncogene fused to an immunoglobulin heavy chain gene requires immunoglobulin light chain for cell surface expression and oncogenic transformation. AB - The protein encoded by the neu protooncogene (human gene symbol NGL for neuro/glioblastoma-derived) is a member of the surface receptor/tyrosine kinase family. Though its structure suggests that it can transduce a transmembrane signal, neither its extracellular ligand nor its critical intracellular substrates are known. To explore the functional properties of the protein encoded by neu, we created a fusion gene that joins the cytoplasmic domain of neu to the extracellular portion of an immunoglobulin heavy chain. The localization of the fusion polypeptide can then be controlled by coexpression with immunoglobulin light chain. In the absence of light chain, the heavy chain-neu polypeptide is expressed intracellularly and has no transforming activity. By contrast, in the presence of light chain the fusion polypeptide is expressed at the cell surface and produces tumorigenic foci. Thus, transformation apparently requires expression at the cell surface, where the neu intracellular domain can interact with components that are localized to the plasma membrane. The fusion protein is active in cellular transformation when the transmembrane domain is derived either from neu or from immunoglobulin, indicating that the neu transmembrane domain is not specifically required for transformation, although neu activation in tumors is known to result from a point mutation in this region. The extracellular immunoglobulin heavy and light chain domains of the fusion protein form a functional binding site that allows antigen to modulate its activity, reversing the transforming effect. PMID- 2903502 TI - Coexistence and gene expression of phenylethanolamine N-methyltransferase, tyrosine hydroxylase, and neuropeptide tyrosine in the rat and bovine adrenal gland: effects of reserpine. AB - Expression and regulation of the catecholamine-synthesizing enzymes phenylethanolamine N-methyltransferase (PNMTase; S-adenosyl-L methionine:phenylethanolamine N-methyltransferase, EC 2.1.1.28) and tyrosine hydroxylase [TyrOHase; tyrosine 3-monooxygenase, L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2] and the coexisting neuropeptide tyrosine (NPY) were studied in rat and bovine adrenal medulla. By using both immunohistochemistry and in situ hybridization, PNMTase- and NPY-positive cells exhibited a close overlap in bovine medulla and were preferentially localized in the outer two-thirds of the medulla. Although TyrOHase and its mRNA were observed in virtually all medullary gland cells, TyrOHase mRNA levels were much higher in the PNMTase- and NPY-positive cells. After administration of the catecholamine-depleting drug reserpine to rats, a brief increase, followed by a dramatic decrease, in the level of PNMTase mRNA was observed in the adrenal medulla. In contrast, mRNA for both TyrOHase and NPY only exhibited an increase, whereby the TyrOHase mRNA peak preceded that of NPY mRNA. Different regulatory mechanisms may thus operate for these three compounds coexisting in the adrenal medulla. PMID- 2903504 TI - Dynamic determination of kinetic parameters for the interaction between polypeptide hormones and cell-surface receptors in the perfused rat liver by the multiple-indicator dilution method. AB - Hepatic elimination of epidermal growth factor (EGF) via receptor-mediated endocytosis was studied by a multiple-indicator dilution method in the isolated perfused rat liver, in which cell polarity and spatial organization are maintained. In this method EGF was given with inulin, an extracellular reference, as a bolus into the portal vein, and dilution curves of both compounds in the hepatic vein effluent were analyzed. Analysis of the dilution curve for EGF, compared with that for somatostatin, which showed no specific binding to isolated liver plasma membranes, resulted as follows: (i) both extraction ratio and distribution volume of 125I-labeled EGF decreased as the injected amount of unlabeled EGF increased; (ii) the ratio plot [ln (inulin/EGF) versus time] of the dilution curve for EGF exhibited an upward straight line initially for a short period of time (approximately equal to 10 sec), whereas the ratio plot [ln (inulin/somatostatin) versus time] of somatostatin gradually decreased. The multiple-indicator dilution method was used for other peptides also. Insulin and glucagon, known to have hepatocyte receptors, behaved similarly to EGF in shape of their ratio plots. Thus, analysis of dilution curves can reveal whether or not the cell surface has receptors for certain peptides. In addition, the dilution curves for EGF at various doses (tracer approximately equal to 30 micrograms) were analyzed simultaneously based on a kinetic model incorporating the perfusion rate, the association rate constant of EGF to surface receptors (kappa on), the dissociation rate constant of EGF from the EGF-receptor complex (kappa off), and the sequestration rate constant of the complex. The kinetic parameters [the dissociation constant (Kd = kappa off/kappa on) and the number of surface receptors] calculated by this analysis were comparable with reported values obtained by in vitro direct binding measurements at equilibrium using liver homogenates. We conclude that the multiple-indicator dilution method is a good tool for analyzing the dynamics of peptide hormones--cell-surface receptor interaction under a condition in which spatial architecture of the liver is maintained. PMID- 2903503 TI - Bipolar cells in the turtle retina are strongly immunoreactive for glutamate. AB - Strong glutamate immunoreactivity was observed by both light and electron microscopy in bipolar cells of the turtle (Pseudemys scripta elegans) retina after postembedding immunohistochemistry. Virtually all bipolar cells showed strong labeling, on average 18 times that of the Muller (glial) cells. The data suggest that both on- and off-center bipolar cells are glutamatergic. Photoreceptors were also labeled, but with a labeling intensity about half that of the bipolar cells. Other types of retinal neurons showed less immunoreactivity, except for a small population of strongly labeled amacrine cells. PMID- 2903505 TI - A glutamate receptor regulates Ca2+ mobilization in hippocampal neurons. AB - We investigated the effect of various excitatory amino acids on intracellular free Ca2+ concentration ( [Ca2+]i) in single mouse hippocampal neurons in vitro by using the Ca2+-sensitive dye fura-2. In normal physiological solution, glutamate, kainate, N-methyl-D-aspartate, and quisqualate all produced increases in [Ca2+]i. When all extracellular Ca2+ was removed, kainate and N-methyl-D aspartate were completely ineffective, but quisqualate and glutamate were able to produce a spike-like Ca2+ transient, presumably reflecting the release of Ca2+ from intracellular stores. Ca2+ transients of similar shape could also be produced by the alpha 1-adrenergic agonist phenylephrine. After the production of a Ca2+ transient a second addition of quisqualate was ineffective unless intracellular stores were refilled by loading the cell with Ca2+ following depolarization in Ca2+-containing medium. None of the conventional excitatory amino acid receptor antagonists inhibited the Ca2+-mobilizing effects of quisqualate. Furthermore alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) was unable to produce Ca2+ mobilization in Ca2+-free medium, although it could produce Ca2+ influx in Ca2+-containing medium. Thus, glutamate can produce mobilization of Ca2+ from intracellular stores in hippocampal neurons by acting on a quisqualate-sensitive but AMPA-insensitive receptor. This receptor is therefore distinct from the quisqualate receptor that produces cell depolarization. The possibility that this Ca2+-mobilizing effect is mediated by inositol triphosphate production is discussed. PMID- 2903508 TI - RFLP analysis in familial polyposis and Gardner syndrome. PMID- 2903506 TI - Alpha 1-adrenergic agonists selectively suppress voltage-dependent K+ current in rat ventricular myocytes. AB - The effects of alpha 1-adrenergic agonists on the waveforms of action potentials and voltage-gated ionic currents were examined in isolated adult rat ventricular myocytes by the whole-cell patch-clamp recording technique. After "puffer" applications of either of two alpha 1 agonists, phenylephrine and methoxamine, action-potential durations were increased. In voltage-clamped cells, phenylephrine (5-20 microM) or methoxamine (5-10 microM) reduced the amplitudes of Ca2+-independent voltage-activated outward K+ currents (Iout); neither the kinetics nor the voltage-dependent properties of Iout were significantly affected. The effects of phenylephrine or methoxamine on Iout were larger and longer-lasting at higher concentrations and after prolonged or repeated exposures; in all experiments, however, Iout recovered completely when puffer applications were discontinued. The suppression of Iout is attributed to the activation of alpha 1-adrenergic receptors, as neither beta- nor alpha 2 adrenergic agonists had measurable effects on Iout; in addition, the effect of phenylephrine was attenuated in the presence of the alpha antagonist phentolamine (10 microM), but not in the presence of the beta antagonist propranolol (10 microM). Voltage-gated Ca2+ currents, in contrast, were not altered measurably by phenylephrine or methoxamine and no currents were activated directly by these agents. Suppression of Iout was also observed during puffer applications of either of two protein kinase C activators, phorbol 12-myristate 13-acetate (10 nM 1 microM) and 1-oleoyl-2-acetylglycerol (60 microM). We conclude that the activation of alpha 1-adrenergic receptors in adult rat ventricular myocytes leads to action-potential prolongation as a result of the specific suppression of Iout and that this effect may be mediated by activation of protein kinase C. PMID- 2903507 TI - Cross-reaction of two different somatostatin antisera with calcitonin gene related peptide. AB - Two different anti-somatostatin antisera, R-101 and OAL-273, cross-react with rat calcitonin gene-related peptide (1-37) (CGRP). CGRP amounts, in excess of 6.25 x 10(-9) M, cross-react with R-101 in the somatostatin radioimmunoassay. CGRP amounts, in excess of 1.6 x 10(-9) M, cross-react with OAL-273. Both CGRP displacement curves are parallel to that of synthetic somatostatin (1-14). Comparison of ID50's shows that the cross-reactivity of CGRP with R-101 and OAL 273 are 0.02 and 0.1% of somatostatin, respectively. PMID- 2903509 TI - Plasma amine metabolites before and after withdrawal from neuroleptic treatment in chronic schizophrenic inpatients. AB - Plasma catecholamine metabolites were measured in paired blood samples from 22 subjects with chronic schizophrenia. One sample was drawn while patients were on a stable dose of neuroleptic medication; the second was drawn 6 weeks after discontinuation of medication. In comparison with baseline values during neuroleptic treatment, there was a significant increase in the plasma concentration of the norepinephrine metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), and a trend toward an increase in the plasma concentration of the dopamine metabolite, homovanillic acid (HVA), in the medication-free subjects. There were no significant correlations between plasma MHPG or HVA concentrations and the corresponding ratings of psychopathology for these patients. PMID- 2903510 TI - Endocrine parameters and biogenic amines in relationship to psychopathology after cholinergic drug challenge (RS-86). AB - The centrally active muscarinic agonist RS-86 elicited a dose-dependent anergic anhedonic syndrome in a double-blind dose-response study in one healthy volunteer. At 4 and 5 mg, RS-86 induced escape from cortisol suppression by dexamethasone parallel to an increase in prolactin. The time course, as well as the absence of increases in plasma epinephrine and growth hormone, suggests that the changes are not due to nonspecific stress. However, there was a slight increase in plasma norepinephrine, tentatively dependent on the dose of RS-86. In 12-hour urine samples the excretion of 3-methoxy-4-hydroxy-phenylglycol and homovanillic acid tended to decrease in a dose-dependent manner, with a subsequent increase during the following nights. No systematic changes occurred in plasma dopamine, serotonin, and cyclic adenosine monophosphate or in plasma and urinary 3,4-dihydroxyphenylacetic acid or urinary vanillylmandelic acid. The findings are discussed in terms of the cholinergic-adrenergic balance hypothesis of affective disorders and biochemical findings in major depression. PMID- 2903511 TI - Polymorphic DNA markers and mental disease. PMID- 2903512 TI - Response to drugs in schizophrenia: the influence of family history, obstetric complications and ventricular enlargement. AB - A prospective study of antipsychotic drug treatment showed no difference in response between schizophrenic in-patients with or without a familial predisposition to the illness (N = 53). All patients received at least 600 mg chlorpromazine equivalents antipsychotic medication for 6 weeks. Ventricle brain ratios, ratings of cortical sulcal widening and a history of obstetric complications also failed to account for the variability, but early age of onset was associated with unsatisfactory response. PMID- 2903514 TI - Proton-induced transformation of Ca2+ channel: possible mechanisms and physiological implications. PMID- 2903513 TI - Obsessive-compulsive beliefs and treatment outcome. AB - Of 49 compulsive ritualizers one-third perceived their obsessive thoughts as a rational and felt that their rituals warded off some unwanted or feared event (the content of their obsessions). The more bizarre the obsessive belief the more strongly it was defended and 12% of cases made no attempt to resist the urge to ritualize. Neither fixity of belief nor resistance to compulsive urges were related to duration of illness. Patients with bizarre and fixed obsessive beliefs responded as well to treatment (all but three received exposure), as did patients whose obsessions were less bizarre and recognized as senseless. There was no difference in outcome between patients who initially found it hard to control their obsessions or never resisted the urge to ritualize and those who initially could control obsessions or resist rituals. One year after starting treatment, patients whose obsessions and compulsions had improved with treatment recognized their irrationality more readily and controlled their compulsive urges more easily. Beliefs appeared to normalize as a function of habituation. PMID- 2903515 TI - GAD-like and TH-like immunoreactivity in ground squirrel retina. PMID- 2903516 TI - Alteration of identified output synapses spared by axotomy. PMID- 2903517 TI - Two different release mechanisms of 3H-GABA induced by glutamate in the rat olfactory bulb. PMID- 2903518 TI - [The supra-aortic blood supply in the Takayasu syndrome determined by digital subtraction angiography]. AB - In a case of Takayasu's aortitis, digital subtraction angiography (DSA) revealed the detailed anatomy of patent intracerebral vessels through intraspinal and cervical collaterals with the only blood supply arising from the left vertebral artery. DSA gives not only anatomical, but also dynamic information, which means the direction of the blood stream is revealed. PMID- 2903519 TI - Immunohistochemical evidence for a co-transmitter role of opioid peptides in primary sensory neurons. PMID- 2903520 TI - Inhibition of lyso-PAF: acetyl-CoA acetyltransferase by salicylates and other compounds. AB - Diflunisal and benoxaprofen (20-100 microM) produced dose-dependent inhibitions of lyso-platelet activating factor: acetyl-CoA acetyltransferase in a lysate of rat pleural neutrophils. Salicylate and aspirin were inhibitory at concentrations of 1 mM and above. Nordihydroguaiaretic acid was a relatively potent inhibitor (I50 = 6 microM). Other compounds, including anti-inflammatory steroids, cyclooxygenase and 5-lipoxygenase inhibitors, appeared ineffective at relevant concentrations. Inhibitions by diflunisal and salicylate occurred at concentrations similar to expected plasma levels in humans at therapeutic doses. An inhibition of platelet-activating factor synthesis may contribute to the antiinflammatory, analgesic, or antipyretic actions of these compounds. PMID- 2903521 TI - The lung in systemic vasculitis. AB - Pulmonary vasculitis is usually caused by one of three disorders: (1) Wegener's granulomatosis (WG); (2) Churg-Strauss syndrome (CSS), or allergic angiitis and granulomatosis; or (3) a nonspecific small vessel systemic necrotizing vasculitis (SNV), or microscopic polyarteritis. WG, the most common cause of lung vasculitis, has features of a granulomatous vasculitis of the upper airway and lung and widespread small vessel vasculitis involving the kidneys and other organs. The features of pulmonary WG overlap with those of malignancy and infectious granulomatous lung disease; accurate diagnosis generally requires open lung biopsy. CSS is defined by the triad of asthma, eosinophilia, and systemic vasculitis. Easily accessible tissues should be biopsied, but the clinical features are so distinctive that tissue biopsy is not invariably required for diagnosis. CSS must be differentiated from other diseases that cause pulmonary infiltrates with eosinophilia, including infections. Nonspecific SNV causes diffuse alveolar hemorrhage due to pulmonary capillaritis. Concomitant segmental necrotizing glomerulonephritis is almost always present. Diagnosis is made by renal biopsy, compatible extrarenal features, exclusion of nonimmune causes of lung hemorrhage, and exclusion of WG to the extent possible. PMID- 2903522 TI - Fowler-Stephens orchiopexy. PMID- 2903523 TI - Neoplasia in cryptorchid men. PMID- 2903524 TI - Carcinoma in situ of the undescended testis. PMID- 2903526 TI - Cryptorchidism and related disorders. PMID- 2903525 TI - Contralateral testicular disease after unilateral testicular injury: current concepts. PMID- 2903527 TI - Embryological controversies in testicular descent. PMID- 2903528 TI - Histopathology of the undescended testis. PMID- 2903529 TI - Diagnostic maneuvers in cryptorchidism. PMID- 2903530 TI - Hormonal treatment of cryptorchidism: role of pituitary gonadal axis. PMID- 2903531 TI - Surgical treatment of cryptorchidism. PMID- 2903532 TI - [Intrinsic sympathicomimetic activity of beta blockers]. PMID- 2903533 TI - [Sleep stages in man--physiological profile and changes induced by psychotropic drugs]. PMID- 2903534 TI - [Clinical studies of the effect of the serotonin precursor, L-5 hydroxytryptophan, on sleep disorders]. PMID- 2903535 TI - [Urinary incontinence induced by neuroleptics--e little known complication]. PMID- 2903536 TI - [Evaluation of the efficacy of the intravenous admixture of aspartate magnesium hydrochloride with beta-mimetics in the treatment of impending premature labor]. PMID- 2903537 TI - Understanding the structure and antigenicity of gonococcal pili. AB - Pili--filamentous protein structures found on the cell surface of many infectious gram-negative bacteria--often are virulence factors that mediate adherence to host epithelial cells. The pilus, a major surface antigen of the gonococcus, is formed by the specific association of thousands of repeating identical protein subunits (pilin). Structural studies of the pilin protein and the pilus fiber may aid the rational design of a peptide-based vaccine by providing information on the antigenic surface of pili that includes the identification of sequence distant antigenic regions that are localized to single areas of the three dimensional structure. Preliminary results suggest that the pilin subunit has structural similarity to the 4-alpha-helix bundle fold in proteins such as the coat protein subunit of tobacco mosaic virus and myohemerythrin. Therefore, the monomeric protein myohemeythrin was used to identify structural correlations for antigenic determinants on 4-alpha-helix bundle proteins such as pilin. PMID- 2903538 TI - Interaction between pap-encoded pilin and adhesin gene products of uropathogenic Escherichia coli. AB - Uropathogenic Escherichia coli are major causative agents of cystitis and pyelonephritis. Most E. coli pyelonephritis isolates express pili encoded by the pyelonephritis-associated pili (pap) gene cluster. The pap DNA sequence encodes pilin monomers that are assembled into pili fibers; pap also encodes adhesins that recent results suggest might be located at the tips of the pilus fibers. The study presented here is a status report of work that has two major goals: to determine (1) if any Pap proteins associate with pili and (2) if Pap proteins not required for pili assembly affect levels of pili-cell surface expression. To address the first aim, antisera to pili were used to precipitate pili from detergent extracts containing 35S-labeled Pap proteins. The results suggested that a protein of 16-kilodaltons apparent molecular mass associated with pili. Other interpretations of the data are discussed. The second aim was addressed by constructing E. coli strains that contained different pap regions. With the use of electron microscopy and a pili ELISA, it was found that E. coli containing a 6.5-kilobase-pair region of pap expressed low levels of pili, but no P-adhesin was detected. Transformation of this E. coli strain with a plasmid containing an additional 3.5-kilobase-pair pap DNA sequence resulted in an eightfold increase in pili expression as well as expression of P adhesin. These results indicated that pili expression was affected by Pap proteins not required for pili assembly. PMID- 2903540 TI - Type 1 fimbriae of Escherichia coli: genetic regulation, morphogenesis, and role in pathogenesis. AB - Over the last several years a number of aspects related to the molecular biology of the type 1 fimbriae of Escherichia coli have been investigated with use of a variety of approaches, including molecular genetics, electron microscopy, and cell biology. With the help of these analytic tools, new insights have emerged. The on-and-off genetic regulation of expression, referred to as phase variation, has been found to be regulated at the level of transcription by the inversion of a 314-base-pair segment of DNA. Morphogenesis of the organelles, which depends on the assembly of processed subunits of 17,000-dalton mass, has been found to proceed from the addition of new subunits at the base, rather than at the tip, of the organelle. Although the precise role of type 1 fimbriae in the pathogenesis of E. coli infections is still somewhat obscure, new data indicate that they significantly potentiate the uptake of nutrients from and the delivery of toxins to eukaryotic cells. PMID- 2903539 TI - Surface proteins of Bordetella pertussis. AB - Bordetella pertussis cells express multiple virulence-associated surface proteins, including adenylate cyclase, agglutinogens 2 and 3, filamentous hemagglutinin, pertussis toxin, and outer-membrane protein (Omp) 30/32 and Omp91. Surface proteins that are not virulence-associated include three peptidoglycan associated Omps of apparent molecular weights 40,000, 25,000, and 18,000. Omp40 is an anion-selective porin and is the most abundant surface protein of virulent and avirulent cells. Three independent approaches--immunomicroscopy, surface radioiodination, and isolation of Triton X-100-insoluble envelope proteins- suggest that the Triton-insoluble fraction of the B. pertussis cell envelope is the outer membrane. Agglutinogens 2 and 3 and filamentous hemagglutinin lie outside the outer membrane, the first two as fimbriae and the last as a microcapsule. Adenylate cyclase and pertussis toxin are present in the outer membrane but may be present transiently or present in small amounts. PMID- 2903541 TI - [Small-cell bronchopulmonary cancer. New data on its cellular biology]. PMID- 2903542 TI - The pathophysiological and pharmacological basis of peptic ulcer therapy. AB - Both genetic and nongenetic factors predispose to ulcer diathesis. At the mucosal level ulcers result from an imbalance between aggressive factors and mucosal defense. Ulcer therapy reduces aggressive forces, bolsters defense, or both. Gastric acid, the major aggressive factor, may have its secretion inhibited or it may be partially neutralized by antacids. H2 receptor antagonists competitively block histamine occupancy of H2 receptors on parietal cells, thereby preventing stimulation of adenylate cyclase, cAMP rises, and activation of protein kinase and H+/K+ATPase. Prostaglandins inhibit acid secretion largely by preventing histamine-induced cAMP rises. Proton pump inhibitors bind H+/K+ATPase. Antimuscarinics inhibit acetylcholine receptors on the parietal cell, thereby blocking Ca2+ entry and subsequent activation of protein kinase and the proton pump. Mucosal defense is enhanced by certain prostaglandins, colloidal bismuth subcitrate and sucralfate. Prostaglandins stimulate secretion of bicarbonate and mucus, among other effects. Colloidal bismuth and sucralfate bind to proteins in the ulcer base and stimulate bicarbonate and mucus secretion, partially, in the case of sucralfate, by increasing endogenous prostanoid synthesis. Sucralfate also binds pepsin and bile acids. Colloidal bismuth temporarily eradicates mucosal colonization by Campylobacter pylori, another putative agent in ulcer diathesis. PMID- 2903543 TI - Gastric enterochromaffin-like cell hyperplasia and neoplasia in the rat: an indirect effect of the histamine H2-receptor antagonist, BL-6341. AB - Oral administration of BL-6341 hydrochloride, a long-acting histamine H2-receptor antagonist, to rats for 2 years at doses of 10, 55 or 300 mg/kg/day resulted in several changes in the fundic (oxyntic) mucosa of the glandular stomach. The most significant alteration was a proliferation of argyrophil endocrine cells that was demonstrated to be enterochromaffin-like (ECL) cells. The ECL cell proliferation consisted of a continuum of changes involving diffuse hyperplasia, focal adenomatous hyperplasia, and carcinoid tumor formation at the highest dose level of 300 mg/kg. At 55 mg/kg only ECL cell hyperplasia occurred, and at the low dose of 10 mg/kg there were no remarkable proliferative changes. The reference compound, cimetidine (950 mg/kg), produced a degree of ECL cell proliferation that was slightly less, but not significantly different than, that observed with 55 mg/kg of BL-6341. Dose-related elevations of serum gastrin were observed with BL-6341, while cimetidine produced hypergastrinemia that was generally intermediate between that produced by the middle and low doses of BL-6341. The hypergastrinemia resulted from the pharmacologic inhibition of acid secretion, which is the negative feedback mechanism controlling the production of gastrin. Only the 300 mg/kg dose of BL-6341 produced a significant, sustained (24 hours) hypergastrinemia and carcinoid tumors. The chronic, sustained hypergastrinemia was considered to be the primary cause of the ECL cell carcinoid neoplasia. All genetic toxicology tests performed with BL-6341 were negative. It was concluded that the demonstrated hypergastrinemia represents an indirect, hormonal, epigenetic mechanism of tumorigenesis. PMID- 2903544 TI - Gastric ECL-cell hyperplasia and carcinoids in rodents following chronic administration of H2-antagonists SK&F 93479 and oxmetidine and omeprazole. AB - The histamine H2-receptor antagonist SK&F 93479 induced gastric neuroendocrine (carcinoid) ECL-cell tumor formation in 6/34 male and 8/37 female rats treated for 22-24 months at 1,000 mg/kg/day po. Focal ECL-cell hyperplasia was present in 21/34 males and 15/37 females, with local infiltration through the muscularis mucosae in half these cases. No focal hyperplasias or carcinoids were present after 200 mg/kg/day po treatment. Investigative studies showed evidence for marked and sustained hypergastrinemia increasing on chronic dosing which was capable of restoring gastric acid secretion and pH to near control values. Using morphometric analysis of immunoperoxidase anti-chromogranin A stained sections, a dose-related and time-dependent neuroendocrine ECL-cell hyperplasia was correlated with the sustained elevated hypergastrinemia. A 21-month mouse oncogenicity study showed no focal neuroendocrine cell hyperplasia or carcinoid tumor induction, but a diffuse neuroendocrine cell hyperplasia and an increase in multifocal glandular hyperplasia of the oxyntic mucosa was observed in mice treated with 1,000 mg/kg SK&F 93479 po. The morphological changes observed in both rat and mouse were considered to be secondary to the hypergastrinemia resulting from the pharmacological suppression of gastric acid secretion by SK&F 93479. These changes were also observed to a more marked degree following omeprazole treatment and were only slight following oxmetidine treatment in the rat. PMID- 2903545 TI - Morphologic stomach findings in rats and mice treated with the H2 receptor antagonists, ICI 125,211 and ICI 162,846. AB - The gross and histopathologic findings seen in the stomachs of rats and mice treated with 2 different H2 receptor antagonists are presented. Studies with the first drug, ICI 125,211, elicited dysplasia/carcinoma lesions in 17 of 828 treated rats with 12 of the 17 lesions occurring in the pyloric region of the stomach. No tumors occurred in mice on study for 18 months. Studies conducted with another drug candidate, ICI 162,846, produced neuroendocrine carcinomas in the stomach of rats and mice. Twenty-five rats out of 312 treated male and female rats had neuroendocrine carcinomas in the gastric fundus with a higher tumor incidence in females. In a 24-month mouse study with ICI 162,846, 45 of 300 treated mice developed neuroendocrine carcinomas in the gastric fundus with a higher incidence in males. PMID- 2903547 TI - Undescended testis--diagnosis, treatment and fertility. PMID- 2903546 TI - [Sulfasalazine or salazosulfapyridine in the treatment of rheumatoid polyarthritis. An open study of 46 patients. Review of the literature]. AB - The SASP was studied in 46 patients with rheumatoid arthritis. The efficacy criteria which were selected (decrease of the sed rate by more than 50 p. cent during the first hour, morning stiffness under 20 minutes, Ritchie's index inferior to 10 and decreased cortisone and NSAID doses), explain that 25 p. cent of the patients are considered as satisfied after 12 months of trial. The patients selected, present severe forms of the disease or forms resistant to other treatments. The improvement appears significant after the first month. Half of the patients left the trial either because of ineffectiveness, or evolutive relapse (21.73 p. cent) or because of side-effects (28.26 p. cent). The most frequently observed disorders and intolerances are of digestive nature. No serious accident is to be deplored. Such results are in accordance with the data from the literature. The SASP must therefore be considered as the fundamental treatment of rheumatoid arthritis. The new galenic forms, dissolving in the gastro-intestinal tract, have enabled to markedly improve the digestive tolerance. PMID- 2903548 TI - Non-union of testis and epididymis. Description of an experimental model in the rat. Effect on testicular descent. AB - Most of the reported anomalies in undescended male gonads involve disruption of continuity in the proximal reproductive tract. In order to study the effect of this anomaly on the testis, an experimental model was developed. 16-day-old Sprague-Dawley rats were operated on. The testes were mobilized through a midline abdominal incision and further dissection was carried out under an operation microscope with 20X magnification. The efferent ducts were dissected free, clamped with a microclip, severed and ligated. The epididymis and testis were separated to the level of the inferior epididymal artery. Following surgery 11 of 35 operated testes (31%) remained in the abdomen while three (9%) descended into the opposite hemiscrotum. One of these atrophied due to torsion. The rest descended normally as did all in the sham-operated group. No surgical complications were seen. At 30-37 days the non-union operated testes were edematous, but no tubular distension was seen. The operative procedure probably involves ligation of lymphatic vessels from the testis as well as ductuli efferentes causing an interstitial edema. PMID- 2903549 TI - Chromosome mapping with DNA markers. AB - New markers called RFLP's (for restriction-fragment length polymorphisms) can indicate the location on a chromosome of a disease-causing gene and serve to identify carriers. With enough markers one can map the human chromosomes--the first step toward an ambitious goal of molecular biology: sequencing the entire human genome. PMID- 2903550 TI - Cellular and molecular mechanisms of drug dependence. AB - The molecular and cellular actions of three classes of abused drugs--opiates, psychostimulants, and ethanol--are reviewed in the context of behavioral studies of drug dependence. The immediate effects of drugs are compared to those observed after long-term exposure. A neurobiological basis for drug dependence is proposed from the linkage between the cellular and behavioral effects of these drugs. PMID- 2903551 TI - Long-term synaptic potentiation. AB - Long-term synaptic potentiation (LTP) is a leading candidate for a synaptic mechanism of rapid learning in mammals. LTP is a persistent increase in synaptic efficacy that can be quickly induced. The biophysical process that controls one type of LTP is formally similar to a synaptic memory mechanism postulated decades ago by the psychologist Donald Hebb. A key aspect of the modification process involves the N-methyl-D-aspartate (NMDA) receptor-ionophore complex. This ionophore allows calcium influx only if the endogenous ligand glutamate binds to the NMDA receptor and if the voltage across the associated channel is also sufficiently depolarized to relieve a magnesium block. According to one popular hypothesis, the resulting increase in the intracellular calcium concentration activates protein kinases that enhance the postsynaptic conductance. Further biophysical and molecular understanding of the modification process should facilitate detailed explorations of the mnemonic functions of LTP. PMID- 2903552 TI - Cryopreservation, culture, and transplantation of human fetal mesencephalic tissue into monkeys. AB - Studies in animals suggest that fetal neural grafts might restore lost neurological function in Parkinson's disease. In monkeys, such grafts survive for many months and reverse signs of parkinsonism, without attendant graft rejection. The successful and reliable application of a similar transplantation procedure to human patients, however, will require neural tissue obtained from human fetal cadavers, with demonstrated cellular identity, viability, and biological safety. In this report, human fetal neural tissue was successfully grafted into the brains of monkeys. Neural tissue was collected from human fetal cadavers after 9 to 12 weeks of gestation and cryopreserved in liquid nitrogen. Viability after up to 2 months of storage was demonstrated by cell culture and by transplantation into monkeys. Cryopreservation and storage of human fetal neural tissue would allow formation of a tissue bank. The stored cells could then be specifically tested to assure their cellular identity, viability, and bacteriological and virological safety before clinical use. The capacity to collect and maintain viable human fetal neural tissue would also facilitate research efforts to understand the development and function of the human brain and provide opportunities to study neurological diseases. PMID- 2903553 TI - A chemically synthesized Antennapedia homeo domain binds to a specific DNA sequence. AB - A peptide 60 residues in length that corresponds to the homeo domain of Antennapedia (Antp), a protein governing development in Drosophila, was synthesized by segment condensation with protected peptide segments prepared on an oxime resin. A footprinting assay showed that the homeo domain binds specifically to a TAA repeat DNA sequence in the Antp gene. Thus the Antp homeo domain has a sequence-specific DNA binding property. The circular dichroism spectra of the homeo domain peptide showed the presence of a significant amount of alpha-helical structure in aqueous solution and in 50 percent trifluoroethanol. The alpha helicity measured in water appears to depend on the peptide concentration, which suggests that the peptide aggregates. These results support the hypothesis that the homeo domain binds to DNA through a helix-turn helix motif. PMID- 2903554 TI - Slow-acting antirheumatic drugs in chronic arthritis of childhood. PMID- 2903555 TI - Sulphasalazine in rheumatoid arthritis. PMID- 2903556 TI - Enterobacteriaceae: composition, structure and function of the cell envelope. PMID- 2903557 TI - [Beta 2 agonists]. PMID- 2903559 TI - [Beta blockers]. PMID- 2903558 TI - [Acromegaly]. PMID- 2903560 TI - [Basic treatment of migraine]. PMID- 2903561 TI - Angina as a symptom of psychiatric illness. AB - We retrospectively studied all patients who had normal coronary angiograms at The Methodist Hospital during the year 1984 (8% of all angiograms). Patients were surveyed eight to 18 months after angiography. Of the 216 patients (83% of total sample), 130 were female and 86 male. Sixty-three percent of the women and 50% of the men satisfied the criteria for generalized anxiety disorder, and 20% satisfied the criteria for panic attacks. On the Brief Symptom Inventory (BSI) Somatization Scale, 64% had scores above the average reported for psychiatric outpatients. Eighty-one percent received only reassurance about the absence of heart disease, and 25% received continuing nitrate therapy in the absence of heart disease. A majority of these patients remain untreated functional "cardiac neurotics" with untreated anxiety symptoms. We make suggestions regarding a clinical profile to identify these patients and appropriate measures to avoid prolonged disability. PMID- 2903562 TI - Somatostatin analogue (SMS 201-995) in patients with gastrinomas. AB - We have examined the effects of the somatostatin analogue (SMS 201-995) in 10 patients with gastrinoma syndrome. Four had hepatic metastases, one had a tumor in a peripancreatic lymph node, two had resectable intrahepatic and intraduodenal gastrinomas, and in three the primary tumor was not found. Acutely, SMS 201-995 decreased acid secretion and restored the BAO/MAO ratio to normal in eight of eight patients. Basal and secretin-stimulated gastrin responses were suppressed but not normalized in eight of eight patients. Suppression of endogenous gastrin restored responsiveness to exogenous gastrin. Treatment for up to 12 months with SMS 201-995 controlled symptoms in six of eight patients, suppressed serum gastrin in three of five, and suppressed acid secretion in three of three patients. Treatment with SMS 201-995 in three patients for 5 months decreased tumor secretion of gastrin and diminished basal acid secretion, an effect that persisted in two of three patients 48 hours after withdrawal of SMS. In patients with metastatic disease who had high levels of gastrin, SMS treatment for 5 to 12 months did not inhibit tumor growth or decrease gastrin levels. SMS treatment arrested progression of tumor growth only in patients who had a reduction in gastrin and gastric acid secretion. We conclude that SMS may be useful in the management of gastrinoma patients by decreasing hypersecretion of gastrin and gastric acid and, over a longer term, may even change tumor capacity to release gastrin and gastric acid secretion. SMS may thus be useful as a palliative agent and as an adjunct to conventional treatment of the gastrinoma syndrome. SMS does not appear to shrink tumor mass in patients with very high basal gastrin levels. PMID- 2903563 TI - The clinical spectrum of Takayasu's arteritis. AB - Takayasu's arteritis is a rare inflammatory disease of the aorta, its major branches, and the pulmonary artery in which the varying anatomic involvement, the time course, and the periodicity of exacerbations give rise to a wide variety of signs and symptoms. We have recently encountered five patients with Takayasu's arteritis whose symptoms and findings demonstrate the clinical spectrum of this disease. All five patients are women, with a current mean age of 41 years. Although findings at initial evaluations included systemic manifestations and elevation of the erythrocyte sedimentation rate in four patients, the fifth patient had a normal erythrocyte sedimentation rate and signs of abdominal aortic occlusion. Two patients had a history of hypertension, and four patients complained of upper- or lower-extremity claudication. Arteriographic examination revealed aortic arch branch vessel involvement (type I) in two patients who also had aortic valvular insufficiency; three patients had combined arch vessel and distal aortic disease (type III). All patients have been maintained on steroid medications, and one patient has undergone a trial of cytotoxic agents. Three patients underwent surgical procedures: aortic valve replacement in two patients, and aortorenal bypass in one patient. Takayasu's arteritis gives rise to a variety of symptoms and findings resulting from the distribution and severity of the inflammatory process. With adequate immunosuppression and selective application of surgical therapy, there is a good prognosis for survival and a return to functional status. PMID- 2903564 TI - Effects of somatostatin and its analogues on dispersed gastric mucosal cells. PMID- 2903565 TI - Ultrastructural characterization and GAD co-localization of somatostatin-like immunoreactive neurons in CA1 of rabbit hippocampus. AB - Immunocytochemical techniques have been used to identify a striking interneuronal population which is immunoreactive for the peptide, somatostatin. The cell population, which is seen most densely in stratum oriens and at the oriens/alveus border of the CA1 region of rabbit hippocampus, was characterized in light and electron microscopic observations. The cells have dendrites which extend parallel to and into the alveus, with occasional processes ascending through stratum pyramidale toward the hippocampal fissure. The dendrites receive numerous synaptic contacts directly onto aspinous dendritic shafts. Axon collaterals ramify profusely within the pyramidale region, and among the proximal apical and basal pyramidal cell dendrites in areas of stratum radiatum and stratum oriens. Somatostatin-like immunoreactive terminals make synaptic contact, primarily of the symmetric type, with the somata and proximal dendrites of pyramidal neurons. Somatostatin-like neurons are found at approximately equal density in the hippocampus of immature (8 days postnatal) and mature (30 days postnatal) rabbit. Double-labelling techniques, to identify both somatostatin-like and glutamic acid decarboxylase (GAD) immunoreactive neurons, demonstrated that a large proportion of the somatostatin neurons were also GABAergic. PMID- 2903566 TI - Acute effects of lithium on dopaminergic responses: iontophoretic studies in the rat visual cortex. AB - The interactions between lithium and cortical dopaminergic receptors were investigated using the iontophoretic technique to record and apply dopaminergic compounds, GABA, acetylcholine and LiCl on neurons in the primary visual cortex of the rat. The main responses to dopamine (DA) or to the D1 agonist (+/- )SKF38393 on spontaneously-active (SA) or visually-driven (VD) units was a prolonged decrease in firing and a reduction in the responsiveness to pulses of acetylcholine. The D1 antagonist SCH23390, applied iontophoretically or intravenously, blocked or attenuated the inhibitory responses to both DA and (+/- )SKF38393. The D2 agonist quinpirole (LY171555) either produced only slight excitations or had no effects on both VD and SA units. The concomitant application of lithium blocked the inhibitory responses to DA and to (+/- )SKF38393 but did not modify the responsiveness to LY171555. In addition, the DA- and (+/- )SKF38393-induced decreases in responsiveness to acetylcholine were also suppressed by lithium. These effects were on dopaminergic mechanisms, since the excitatory responses to acetylcholine alone as well as the inhibitions caused by GABA were unchanged by the application of lithium. These results imply that the modifications in sensitivity to dopaminergic agents induced by lithium are mediated by dopamine D1 receptors and are discussed in relation to adenylate cyclase. PMID- 2903567 TI - Somatostatin and neuropeptide Y immunoreactivity in Parkinson's disease dementia with Alzheimer's changes. AB - Somatostatin-like immunoreactivity (SLI) and neuropeptide Y-like immunoreactivity (NPYLI) were measured in postmortem brain tissue from 12 control patients and 13 demented Parkinsonian patients who had Alzheimer-type cortical pathology. Twenty two cortical regions were examined. Significant reductions in cortical SLI were found in 17 regions, while significant reductions in cortical NPYLI were found in nine regions. The reductions in SLI were typically 50-60%, while NPYLI reductions were 20-30%. These findings are similar to those in Alzheimer's disease (AD) and are consistent with a previous report of a dissociation between reductions in SLI and NPYLI in Parkinson's disease (PD) with dementia. PMID- 2903568 TI - Electrophysiological and pharmacological characterization of identified nigrostriatal and mesoaccumbens dopamine neurons in the rat. AB - Extracellular single-unit recording techniques were used to compare the basal activity and pharmacological responsiveness of identified nigrostriatal and mesoaccumbens dopamine (DA)-containing neurons. The projection area of each DA cell was determined by antidromic activation techniques. The forebrain stimulation used for the cell identification procedure did not alter the pharmacological responsiveness of DA neurons; the inhibitory effect of apomorphine (and d-amphetamine) was identical when stimulation was applied either prior to or following drug administration. Analysis of the spike discharge pattern revealed that a higher proportion of mesoaccumbens DA cells exhibited burst-firing activity. Although the firing pattern of the two populations of burst-firing DA cells was similar in many regards, mesoaccumbens DA cells exhibited a longer postburst inhibition than did nigrostriatal DA cells. Each of the DA agonists, apomorphine, pergolide, B-HT 920, and d-amphetamine, inhibited nigrostriatal and mesoaccumbens DA neuronal activity in a similar fashion. However, there was a marked population difference in the recovery of cell firing in the 10 minutes following apomorphine-induced inhibition; the recovery of mesoaccumbens spike discharges was considerably slower. Although this population difference was apparent to some extent following administration of pergolide or B HT 920 (but not d-amphetamine), it was considerably less marked. The present findings are discussed with respect to the known regulatory control of midbrain DA neurons. PMID- 2903569 TI - A1 noradrenergic action on medial preoptic-medial septal neurons: a neuropharmacological study. AB - In an attempt to determine whether the excitatory and inhibitory orthodromic responses of single medial preoptic-medial septal (MPO-S) neurons to discrete electrical stimulation of the A1 noradrenergic region were mediated specifically by norepinephrine (NE) and involved different types of adrenoreceptors, a series of electrophysiological and neuropharmacological experiments was conducted. Extracellular single unit recording and local drug application techniques were used in female rats under urethane anesthesia. Chemical lesion of the catecholaminergic nerve terminal plexus in the medial preoptic area with 6 hydroxydopamine abolished both excitatory and inhibitory orthodromic effects of A1 region stimulation on MPO-S neurons, suggesting the noradrenergic nature of the effects. This conclusion was corroborated by the observation that the orthodromic effects were mimicked by locally applied exogenous NE. The excitatory effects were reliably mimicked by a low concentration of NE (0.5 mM; in-barrel concentration) and methoxamine (1.0 mM, an alpha-1 agonist), but not by either low or high concentrations (1 and 100 mM) of clonidine (an alpha-2 agonist) and isoproterenol (a beta agonist). The inhibitory orthodromic effects of A1 region stimulation were reliably mimicked by a high concentration of NE (50 mM), clonidine (100 mM) and isoproterenol (100 mM), but not by a low concentration of NE (0.5 mM), methoxamine (1 mM), clonidine (1 mM) or isoproterenol (1 mM). A high concentration (100 mM) of methoxamine mimicked the inhibitory effects less than 40% of the time. The low concentration (0.5 mM) NE-induced excitation that matched the excitatory orthodromic effect of A1 region stimulation was blocked by phentolamine (100 mM), an alpha blocker, but not by timolol (100 mM), a beta blocker. On the other hand, the high concentration (50 mM) NE-induced inhibition that matched the inhibitory orthodromic effect of A1 region stimulation was blocked by timolol, but not by phentolamine. Taken together, the present results are consistent with the hypotheses that the ascending noradrenergic projections from the A1 region affect the excitability of MPO-S neurons directly through NE and that the excitatory and inhibitory orthodromic effects involve different types of adrenoreceptors, i.e., alpha-1 and beta receptors, respectively. PMID- 2903570 TI - Increased neuronal responsiveness to cholecystokinin and dopamine induced by lesioning mesolimbic dopaminergic neurons: an electrophysiological study in the rat. AB - In the rat, cholecystokinin (CCK) and dopamine (DA) coexist in a subpopulation of neurons of the ventral tegmental area (VTA) projecting to the nucleus accumbens. However, in the dorsal hippocampus, dopaminergic projections from the VTA do not contain CCK, the latter neurotransmitter being mainly localized in intrinsic hippocampal neurons. The present experiments were undertaken in order to compare the interactions of CCK and DA and the effects of lesioning VTA dopaminergic neurons in a region where these neurotransmitters coexist and in one where they do not. The effects of microiontophoretic applications of CCK, kainate (KA), glutamate (GLU) and DA were determined in control rats and in rats pretreated with a local injection of 6-hydroxydopamine (6-OHDA) in the VTA. In the nucleus accumbens and in the hippocampus of intact rats, DA exerted a similar depressant effect whether applied during CCK-, KA- or GLU-induced activations. The 6-OHDA lesion enhanced responsiveness of accumbens neurons to KA, GLU and CCK (the responsiveness to this latter peptide being increased by more than 15-fold) and the depressant effect of DA when applied during neuronal activation by KA or GLU but not when the same neurons were activated with CCK. In the dorsal hippocampus, the 6-OHDA lesion enhanced neuronal responsiveness to KA and DA in the CA1, but not in the CA3 region, whereas the responsiveness to CCK remained unchanged in both regions. These results suggest a physiological role for the coexistence of CCK and DA in the nucleus accumbens. The induction of a supersensitivity to DA in the CA1, but not in the CA3, region of the dorsal hippocampus following a VTA lesion is consistent with the regional distribution of the dopaminergic innervation in this structure. PMID- 2903571 TI - [Laboratory assessment of HIV infection and its sequelae]. PMID- 2903572 TI - [Niaprazine and side effects in pediatrics. Cooperative evaluation of French centers of pharmacovigilance]. PMID- 2903573 TI - Thrombin-independent activation of platelet factor XIII by endogenous platelet acid protease. AB - Platelets contain factor XIII, an A subunit zymogen form of transglutaminase (TGase), that is activated by thrombin. In addition a thrombin-independent TGase (A#) was observed. A# was formed in platelet preparations lysed at acid pH, and its generation inhibited by protease inhibitors and alkaline pH. When maximal A# activity was generated in acidified lysates no further TGase activity could be induced by subsequent treatment with thrombin. Both FXIII zymogen and A# copurified as for FXIII, from either alkaline or from acidified platelet lysates respectively, by the conventional procedure. The pH optima, Km's for NN dimethyl casein, molecular weights, heat lability of active forms, requirements for calcium and reducing agents, and immunological characteristics of both TGases were the same. Studies with inhibitor substrates suggested that a thrombin-like cathepsin C or carboxypeptidase was responsible for A# formation. Purified FXIII zymogen could be activated directly by cathepsin C. Thus, the predominant, and probably only, TGase of platelets is factor XIII, which may be activated either by thrombin or by endogenous platelet acid protease(s). PMID- 2903574 TI - Haemophilia A in a female: study of a family using intragenic and extragenic restriction site polymorphisms. AB - Restriction fragment length polymorphisms (RFLPs) were studied in a large Algerian family which includes 6 haemophiliacs and a previously described case of female haemophilia A. The female propositus is 66 years old with a normal karyotype. Her parents are first cousins. Her 3 sons are haemophiliacs and her 3 daughters with affected children are obligate carriers. The proband has an excessive bleeding tendency and markedly reduced levels of F.VIII (VIII C 0.03 U/ml, VIII Ag 0.01 U/ml) with elevated vWF Ag (2.30 U/ml), similar to the levels observed in affected males from the family. Four RFLPs can be identified by Southern blotting after digesting genomic DNA with the restriction enzymes Bcl I, Bgl I, Kpn I/Xba I and Taq I and hybridization with a 647 bp Stu I/Sca I F.VIII genomic probe, a 1.8 Kb EcoRI F.VIII cDNA probe, a 1.0 Kb EcoRI/Sst I fragment of intron 22 and the extragenic probe ST 14, respectively. With these four RFLPs, the propositus was found to be homozygous for the alleles segregating in this family with the abnormal X-chromosome. The carrier status was proven in a granddaughter and excluded in another. In conclusion, this RFLP linkage analysis is another argument to suggest that the propositus, a rare case of female haemophilia, is homozygous for the abnormal gene. PMID- 2903575 TI - Sulphasalazine increases fibrinolysis in the anaesthetised rat. PMID- 2903576 TI - Platelet function and plasma fibrinogen and their relations to gender, smoking habits, obesity and beta-blocker treatment in young survivors of myocardial infarction. AB - Seventy-three (58 men and 15 women) survivors of myocardial infarction below 45 years of age and 73 healthy matched controls were investigated regarding in vitro platelet aggregability to ADP and collagen, platelet sensitivity to prostacyclin and plasma levels of beta-thromboglobulin, platelet factor 4 and fibrinogen. The patients, studied 3-6 months after the acute event, had a reduced platelet sensitivity to prostacyclin. They did not differ from the controls regarding the other platelet function tests. Females had higher platelet reactivity than men. Smoking, obesity or beta-blocker treatment did not influence platelet function. The patients had higher fibrinogen levels than the controls. Gender did not influence, while smoking and obesity increased plasma fibrinogen. Patients on beta-blockade had lower fibrinogen levels than patients without this therapy. The high fibrinogen level and the low platelet sensitivity to prostacyclin might indicate an increased thrombotic liability in young myocardial infarction patients. PMID- 2903577 TI - Cytofluorometric identification of plasmin-sensitive factor XIIIa binding to platelets. AB - We have investigated the binding of blood coagulation factor XIIIa to thrombin stimulated platelets using cytofluorometric analysis. Washed thrombin-stimulated platelets bound exogenously added factor XIIIa in a calcium-dependent reaction. The expression of endogenous platelet factor XIII was also detected on the surface of thrombin-stimulated platelets. When fluorescence analysis was performed based on particle size, factor XIIIa bound to the surface of greater than 95% of particles which contained more than one platelet, but only 50% of single platelets. The binding of factor XIIIa to thrombin-stimulated platelets was inhibited by plasmin. Plasmin also inhibited thrombin-dependent expression of the factor XIIIa binding site on platelets. Experiments in which thrombin stimulated platelets were incubated with factor XIIIa in the presence of 125I dimethylcasein or 3H-putrescine demonstrated that platelets bear both glutamyl and lysyl substrates for factor XIIIa. Thrombin increased the expression of factor XIIIa substrates by platelets. Plasmin inhibited both the expression of factor XIIIa substrates and degraded them. The binding of factor XIIIa to thrombin-stimulated platelets and the availability of factor XIIIa substrates on the platelet surface could provide a mechanism by which factor XIIIa stabilizes the hemostatic plug by promoting crosslinking reactions between platelet membrane proteins and adhesive glycoproteins. In contrast, plasmin inhibition of factor XIIIa binding and crosslinking could disrupt hemostasis. PMID- 2903578 TI - [A case of food poisoning caused by C. perfringens]. AB - A case of food borne infection among a hundred inhabitants of a home for the old aged, caused by Clostridium perfringens (Clostridium welchii) following consumption of a filled veal roll is reported. PMID- 2903579 TI - Expanded use of the right and left internal mammary arteries for myocardial revascularization. AB - While the use of the left internal mammary artery (IMA) has become routine in many cardiac surgery units there is some reluctance to utilize the right IMA. The reasons for this are the higher morbidity and mortality observed in the initial experience with bilateral IMA grafting, the limited length of the right IMA, and its potential injury in reoperations when used to revascularize the left anterior descending artery. In this series of 50 patients the right IMA was used as a conduit for myocardial revascularization. One hundred and fifty-nine coronary vessels were grafted (3.2 per patient) 67.3% with IMA and only 32.7% with vein grafts. The right IMA was used for 51 anastomoses and the left for 56, either as simple, sequential or Y type grafts. The refinement of techniques for constructing the IMA grafts used in this series show that the right IMA can reach in most of the cases the anastomotic sites of the right coronary artery beyond the acute margin of the heart, and it is hoped that the lateral positioning of the IMA pedicles will lessen the chance of graft injury at reoperation. On the basis of early clinical results (2% mortality and 4% sternal complications), the application of the right IMA seems justified electively for the revascularization of both left and right coronary artery systems or as a free graft in conjunction with the left IMA. PMID- 2903580 TI - Does low-dose propranolol reduce the incidence of supraventricular tachyarrhythmias following myocardial revascularisation? A clinical study. AB - During 1986, 343 consecutive patients who underwent isolated coronary bypass grafting were given 10 mg of propranolol three times daily for six postoperative weeks to help prevent supraventricular tachyarrhythmias. The incidence of these arrhythmias in this group was compared to that in a similar group of 337 consecutive patients who underwent coronary surgery in 1984 at the same institution and did not receive propranolol. There was no significant difference in the overall incidence of such arrhythmias between the propranolol group (10.8%) and the control group (10.4%). In preoperatively beta-blocked patients, the arrhythmia incidence in the propranolol group (9.9%) was lower than that in the control group (13.8%) but the difference did not achieve statistical significance. The two groups were also similar with respect to the ventricular response rates at the onset of the arrhythmia and the effectiveness of therapeutic intervention. These results suggest that propranolol in the above dosage does not significantly reduce the incidence of supraventricular tachyarrhythmias after myocardial revascularisation. PMID- 2903581 TI - Supraventricular tachyarrhythmias after coronary bypass surgery--a double blind randomized trial of prophylactic low dose propranolol. AB - In the present study 75 patients were double blind randomized either to receive 10 mg propranolol orally 4 times a day (35 patients) or a placebo (40 patients). Episodes of clinically important supraventricular tachyarrhythmias were recorded in the first 4 postoperative days. They appeared in 5 of 35 patients receiving propranolol and in 5 of 40 patients receiving placebo (no statistically significant difference). In conclusion this study indicates the need for further evaluation to clarify if low-dose propranolol or any other drug is effective in reducing the frequency of SVT in the early postoperative period after coronary artery bypass surgery. PMID- 2903582 TI - HLA-DR and -DQ DNA genotyping in seven populations of Asia-Oceania and Australia. AB - Haplotype patterns of HLA-DR and -DQ restriction fragment length polymorphisms (RFLPs) were compared in seven populations in the region of Asia-Oceania: Australian Caucasoids, Melanesians, micronesians, Polynesians, Chinese, Koreans, and Japanese. Several DR beta RFLP patterns, including those correlating with DR2, 4,5, w6, 7 and w8 in Caucasoids, were associated with multiple DQ alpha/DQ beta RFLP haplotypes, of which only two occurred universally - one associated with DR4 and one with DR5. RFLPs revealed new population or group specific characteristics, which had not been previously discovered using serological or cellular HLA typing techniques. The populations of Asia-Oceania have some features of the class II RFLPs in common, which are distinctly different from Caucasoids. On the other hand, a number of characteristics distinguish between the various Asian and Pacific groups. This study demonstrates the power of RFLP analysis of closely linked genes in population genetics, and shows the value of ethnic comparisons in further characterizing the polymorphisms of the HLA class II genes. PMID- 2903583 TI - DQ Wa gives rise to a DQ beta restriction fragment pattern indistinguishable from that of the DQw3.2 sub-type of DQw3. AB - DQ beta restriction fragment patterns have been obtained from five DRw8 cell lines homozygous for the null DQ allele, DQWa. The enzymes Bgl II, Bam HI and Pvu II generate DQ beta patterns which are indistinguishable from those obtained from cell lines homozygous for DQw3.2. PMID- 2903584 TI - [The method of dry chemical analysis of trout blood with Reflotron]. AB - Using blood, plasma and serum of rainbow trout conventional and dry-chemical methods (Reflotron) were compared regarding gamma-GT, hemoglobin (Hb), triglycerides (TG), cholesterin (Chol), and glucose (Gluc). Both methods failed to detect gamma-GT in trout. The dry-chemical analysis of Hb was disturbed by the nuclei of the erythrocytes. Plasma and/or serum showed to be convenient for the dry-chemical assay of TG, Chol and Gluc. The results of the dry-chemical analysis of TG had to be corrected by a factor. PMID- 2903586 TI - The effectiveness of antivenom in countering the actions of box-jellyfish (Chironex fleckeri) nematocyst toxins in mice. AB - The neutralizing ability of commercially available antivenom prepared against 'milked' box-jellyfish (Chironex fleckeri) venom was tested intravenously in mice against crude nematocyst venom obtained by crushing isolated nematocysts and against each of two lethal toxins (T1 and T2) present in this venom. The in vitro neutralizing ability of the antivenom against crude venom was reduced markedly compared with its reported neutralizing ability against 'milked' venom whilst the in vivo neutralizing ability of the antivenom tested in both prophylactic and rescue experiments involving crude nematocyst venom was reduced approximately threefold. When tested in vitro and prophylactically in vivo the neutralizing ability of the antivenom was much more pronounced against T2 than against T1. This finding was in accord with the view that T1 was absent from the 'milked' venom against which the antivenom was prepared. Doses of crude venom in excess of twice the lethal dose killed mice within 2-3 min emphasizing the need for speed in the administration of antivenom. PMID- 2903585 TI - S-(1,2-dichloro-[14C]vinyl)-L-cysteine (DCVC) in the mouse kidney: correlation between tissue-binding and toxicity. AB - Uniformly 14C-labeled DCVC and unlabeled DCVC were synthesized and used for autoradiographical and histopathological studies. Four hours after administration of [14C]DCVC (25 mg/kg body wt), a strong binding of radioactivity was observed in the straight proximal tubular cells. Later, the radioactivity was redistributed from the proximal tubules to scattered foci in the kidney medulla, suggesting desquamation and tubular transport of labeled epithelial cells. The redistribution was less pronounced at a lower [14C]DCVC dose (5 mg/kg body wt). Localization of [14C]DCVC was also observed in the liver, exocrine pancreas, and stomach (fundal part), although at a lower level than in the kidney. While the low dose (5 mg/kg body wt) produced a moderate lesion in the straight proximal tubules 24 hr after DCVC, the high dose (25 mg/kg body wt) not only induced a more pronounced lesion in this tubular segment but also extended the lesion to other tubular segments, including the subcapsular region. The results indicate binding of (a) vinyl-containing metabolite(s) to the straight portion of the proximal tubules, where a primary lesion is subsequently developed. Depending on dose, a "secondary" lesion appears in the subcapsular region, topographically different from the DCVC-binding region. PMID- 2903587 TI - Isolation and characterization of three lethal and hemolytic toxins from the sea anemone Actinia equina L. AB - Lethal and hemolytic toxins were purified by acetone precipitation, Sephadex G 50, CM-cellulose and CM-Sephadex column chromatography from the tentacles and bodies of the sea anemone Actinia equina. The isolated toxins, with a mol. wt of 19,000 determined by SDS-polyacrylamide gel electrophoresis, differed only slightly in amino acid composition and had a high tryptophan content. The isoelectric points were estimated to be 9.8 for equinatoxin I and 10.5 for equinatoxins II and III. The pure toxins exhibited high lethal potency; the acute i.v. LD50 in mice of equinatoxins I, II and III were 23, 35 and 83 micrograms/kg, respectively. The sigmoidal time course of hemolysis is characteristic of toxins. PMID- 2903589 TI - PEHPS medium: an alternative for axenic cultivation of Entamoeba histolytica and E. invadens. AB - Knowledge of Entamoeba histolytica biology in the last 17 years has been acquired largely as a consequence of this parasite's axenic cultivation in TPS-1 or TYI-S 33 media. Unfortunately, there are often low yields in these media, due to variability of their main components, Panmede and yeast extract. We describe a medium, PEHPS, of which the main components are extracts of ox liver, and ox and swine pancreas (EHP). 5 strains of E. histolytica and 2 of E. invadens were quickly and easily adapted to PEHPS and serially cultivated for 3 years. Yields progressively rose initially, and then became stable. Depending on the strain, average yields in the last 6 months of this study were 1.3 to 3.1 x 10(5) amoebae/ml for E. histolytica and 5.5 to 5.7 x 10(5) for E. invadens. All the 18 EHP batches tested supported vigorous amoebal growth. PEHPS had 2 additional advantages: (a) it was stable at 4 degrees C or 25 degrees C for 9 months, and at -10 degrees C for at least 2 years, and (b) it supported amoebal growth with inocula as low as one trophozoite/ml. PEHPS avoids the variability shown by TPS-1 and TYI-S-33, and could therefore be a good alternative for axenic amoebal cultivation. PMID- 2903588 TI - Effects of hexavalent chromium on trout mitochondria. AB - Trout liver mitochondria were incubated in the presence of micromolar concentration of potassium dichromate (Cr(VI)) under several experimental conditions. Cr(VI) strongly inhibited both state 3 and state 4 of respiration supplemented by NAD-linked substrates; it also slightly affected the respiration of FAD-linked substrates. Evidence is provided that the respiratory inhibition induced by dichromate is partially coupled to the Cr(VI) reduction mechanism occurring in mitochondria. PMID- 2903590 TI - Treatment of acute toxaemic fascioliasis. PMID- 2903591 TI - Conventional management of the brain-dead potential multi-organ donor. PMID- 2903592 TI - Office urodynamics. AB - Each urologist can best form his or her own set of indications for and techniques of urodynamic evaluation or referral. Thus, what constitutes "office urodynamics" in one practice does not in another. The practicing urologist should at least have access to filling cystometry, flowmetry, residual urine determination, and voiding cystourethrography. All but the last named are certainly compatible with any office practice. PMID- 2903593 TI - The activity of diagnostic enzymes and the concentration of lipids in the blood vessels of cattle. AB - Blood vessel walls are shown to contain creatine phosphokinase, lactate dehydrogenase, gamma glutamyl transpeptidase and aspartate transaminase activity. The activity of these enzymes in the serum may be enhanced by leakage from damaged blood vessels. The activity of the enzymes alanine transaminase and alkaline phosphatase as well as the content of triglycerides, cholesterol and lipoproteins are very low in the vascular tissue and are unlikely to be of diagnostic value in vascular tissue injury. PMID- 2903594 TI - [Initial results of genetic carrier diagnosis in risk pedigrees with hemophilia A and B in East Germany]. AB - In 7 families at risk for hemophilia A 42 individuals were evaluated by the Taq I polymorphism of the extragenic probe St 14.1 and the Bcl I as well the Hind III polymorphism of the intragenic probe F8e16-19. 15 out of 20 females of the core families were identified as carriers, under them all of the obligate heterozygotes. 5 individuals were excluded as carriers. The heterozygosity for each of the RFLPs was found to be between 30% and 79%. Combining the single data in 96% heterozygosity was found under the individuals tested. A linkage disequilibrium was found between the Bcl I and Hind III polymorphismus of the probe F8e16-19. A family at risk for hemophilia B including 5 individuals was studied using the Taq I and Xmn I polymorphisms of the probe P1. In one of two females the carrier state could be excluded in the other one confirmed. PMID- 2903595 TI - [Modification of hemorheologic parameters by beta-receptor blockers with special reference to propranolol and talinolol]. AB - There are no systematic and complex investigations regarding the hemorheologic action of the betablockers propranolol and talinolol. The results on the other ones are contradictory. On the basis of a critical survey of the literature, in vitro-experiments and studies in animals (rats) and humans may conclude that there are no remarkable deteriorations of rheological parameters in the therapeutic dose range. This is valid for diseases only where the haemodynamic regulation doesn't prevail. PMID- 2903596 TI - Pharmacological methods for the prevention of first and recurrent bleeding from esophagogastric varices. AB - Drug candidates for the prevention of first and recurrent variceal bleeding include 1) vasoconstrictors, 2) vasodilators and 3) various drugs increasing lower esophageal sphincter pressure. 1) Nonselective and beta 2-selective beta adrenergic blockers act through vasoconstriction at the level of the splanchnic arterioles, which adds to the effect of decreased cardiac output. Nonselective beta-blockers decrease portal pressure in most but not all patients by about 10 15%. Azygos venous blood flow, however, is decreased up to 40% in virtually all patients. Data on the efficacy of the nonselective beta-blocker propranolol in the prevention of recurrent variceal hemorrhage derived from prospective, placebo controlled clinical trials are controversial. While one study showed a decrease in both rebleeding rates and long-term mortality in alcoholic cirrhotics with good liver function, these positive results were not confirmed by several subsequent trials. It has been argued that this discrepancy might be the consequence, at least in part, of differences in patient selection. In contrast, three randomized trials did not show any difference in rebleeding rates and survival between propranolol and endoscopic sclerotherapy thus indicating that propranolol might be useful for the prevention of variceal rebleeding. Preliminary results of placebo-controlled trials of propranolol and nadolol for the primary prophylaxis of variceal bleeding also suggest a potential role for beta-blockers in the treatment of portal hypertension. 2) Vasodilator candidates in the treatment of portal hypertension are nitrates, calcium channel blockers, serotonin antagonists, peripheral alpha-adrenergic blockers like prazosine and central alpha-stimulators such as clonidine. The action of nitrates is most probably mediated by reflex splanchnic vasoconstriction consequent on peripheral systemic vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903597 TI - [Somatostatin deficiency, hyperinsulinism and thrombocyte aggregation in psoriasis]. AB - In 59 patients suffering from chronic psoriasis, we tested the therapeutic effects of yohimbine and colchicine. It is well known that yohimbine, an alpha 2 adrenoceptor-blocking agent, reduces the secretion of insulin and the platelet factors. 85% of our psoriatic patients showed decreased values for somatostatin, in association with hyperinsulinemia (88%) and low platelet counts. Successful therapy with yohimbine resulted in the normalization of the pathological blood levels. PMID- 2903598 TI - [Synaptic transmission in the receptors of the lateral acoustic system]. PMID- 2903599 TI - [The neurotrophic role of thiamine]. PMID- 2903600 TI - [Catatonic psychoses in adolescence--a case report of clinical aspects and therapy]. AB - Because catatonic psychosis in childhood and adolescence is rare we have only scanty knowledge about the clinical picture, treatment and prognosis. Based on a single case study these aspects are discussed with respect to treatment course and outcome. A multidimensional treatment concept integrating neuroleptic treatment, individual and family therapy, and physical and occupational therapy seems to be the best approach to the severe affective and cognitive deficits. PMID- 2903601 TI - [Serologic diagnosis of mild, unclear and asymptomatic forms of hemorrhagic fever with renal syndrome]. AB - The use of the serological method (the indirect fluorescent antibody test) for the examination of 255 persons coming in contact with patients having hemorrhagic fever with the renal syndrome (HFRS) in the foci of this infection where outbreaks of group infection had been registered made it possible to detect mild, unclear and asymptomatic forms of HFRS in 17.7-20.9% of cases. The simultaneous titration of 317 serum samples with two antigens revealed that HFRS virus of serotype 1, similar to strain Hantaan from Korea, may cause, besides the classical forms of the disease, the development of mild and asymptomatic forms of this infection. PMID- 2903602 TI - Metoclopramide and ureteric colic. AB - The pain-reducing property of metoclopramide (Primperan) was compared with that of a narcotic combination drug (Spasmofen) in a double-blind study on 40 patients with ureteric colic. The tested drugs had equal pain-reducing capacity and no serious side-effects were noticed. Metoclopramide appears to be an alternative when inhibitors of prostaglandin synthesis or narcotics are contraindicated. PMID- 2903603 TI - [The use of preanesthetic drugs and general anesthetics in hepatic insufficiency]. PMID- 2903604 TI - Cardiovascular responses caused by the combination of lidocaine and vecuronium in the induction of general anaesthesia. AB - Fentanyl, vecuronium and enflurane may cause bradyarrhythmias during anaesthesia. Lidocaine administered before endotracheal intubation may interact synergistically with these agents. In this randomized and double-blind study, lidocaine 1 mg kg-1 (24 patients) or saline (20 patients) was given, immediately after glycopyrrolate 5 micrograms kg-1, fentanyl 1.5 micrograms ml-1 and thiopentone 3-5 mg kg-1, together with vecuronium 0.1 mg kg-1 as a rapid i.v. injection to healthy (ASA 1) surgical patients. Enflurane 0.8% was included in the inhaled gases 10 min and enflurane 1.6% 25 min after lidocaine administration. The plasma concentrations of lidocaine rose to a mean level of 3.1 micrograms ml-1 (maximum 7.1 micrograms ml-1) which may affect the electrical conduction at various sites in the heart. There were no statistically significant differences in arterial blood pressures or heart rates during anaesthesia between the groups. The incidence of junctional rhythm was 7/24 patients in the lidocaine group and 5/20 patients in the saline group. Three patients in the lidocaine group, and two patients in the control group developed junctional rhythm immediately after intubation. The plasma concentrations of vecuronium were unaffected by lidocaine. The ratio of the unbound lidocaine to plasma protein bound lidocaine was at the expected level and did not differ significantly 2 and 10 min after the injection. PMID- 2903605 TI - Intravenous infusion of midazolam, propofol and vecuronium in a patient with severe tetanus. AB - An adult patient with severe tetanus was successfully treated with alternating long-term infusions of propofol (20-80 mg/h, 8 + 3 days) and midazolam (5-15 mg/h, 29 days) for sedation, and with vecuronium infusion (6-8 mg/h, 35 days) for muscle relaxation. In addition, continuous infusion of labetalol (10-20 mg/h, 39 days) was given to control arterial blood pressure. Blood samples were taken daily for assays of propofol, midazolam and vecuronium plasma concentrations. No accumulation of propofol and vecuronium could be detected. There was an increase in liver enzyme activity at the end of the first 8-day propofol infusion. During the 4-week midazolam infusion, there were two marked plasma concentration peaks at times when the infusion rate was fairly stable. These changes coincided with pulmonary infection (C-reactive protein elevated) and ciprofloxacin treatment. The patient awoke rapidly after the last propofol infusion. He was unable to recall anything about his stay in the intensive care unit. PMID- 2903606 TI - Neuropeptide Y, somatostatin, and cholecystokinin neurone preservation in anaplastic astrocytomas. AB - Using immunohistochemistry, well-preserved neuronal cell bodies and fibres containing neuropeptide Y, somatostatin, and cholecystokinin immunoreactivity have been identified in all seven supratentorial anaplastic astrocytomas studied. These neurones have been shown not only on the edge but also in the depth of the neoplastic tissue. These neuropeptides were not present in 18 other intracranial tumours (3 astrocytomas, 1 subependymoma, 8 glioblastoma multiformes, 1 meningioma, and 5 metastases). In all 25 intracranial tumours studied, no immunoreactivity was found for vasoactive intestinal polypeptide, substance P, methionine-enkephalin, leucine-enkephalin, synenkephalin, neurophysin I-II, and corticotropin releasing factor. PMID- 2903607 TI - Esthesioneuroblastoma: a nasal catecholamine-producing tumor of neural crest origin. Demonstration of tyrosine hydroxylase-immunoreactive tumor cells. AB - An esthesioneuroblastoma in a 16-year-old male was studied ultrastructurally and immunohistochemically, using antiserum against tyrosine hydroxylase (TH), a rate limiting enzyme in the catecholamine-synthesizing pathway. Tumor cells were fairly uniform in appearance, showing scanty eosinophilic cytoplasm and round to oval hyperchromatic nuclei, and were arranged in nests and cords of various sizes. Ultrastructurally, individual tumor cells had well-developed cell organelles including polyribosomes, microtubules, intermediate filaments, centrioles, Golgi apparatus and mitochondria. Secretory-like granules were occasionally found, predominantly in the cell processes. Immunohistochemically, many tumor cells were shown to be immunoreactive for TH. This finding strongly suggested that the present tumor was capable of producing catecholamines and that it might be derived from certain sympathetic neuronal cell nests in the superior nasal cavity. PMID- 2903608 TI - Laser welding of titanium in dentistry. AB - Unalloyed titanium of the quality used for osseointegrated implants by the method of Branemark is also sometimes used for the metallic part of the prosthetic superstructure placed on the fixtures and for crowns and bridges of conventional type. Forty bars of titanium, 8 of ASTM B 348 grade-1 quality and 32 of ASTM B 348 grade-2 quality, were laser-welded, using dissimilar laser joint variables. Tensile strength, 0.2% proof stress, and percentage elongation of the welded bars were measured and compared with the corresponding values for the titanium bars as delivered and with those of brazed type-3 gold alloy bars of similar dimensions. The type of fracture was evaluated from fractographs. The results showed that the use of certain defined laser joint variables during welding produced values for the mechanical properties studied which were more favorable than those obtained from the brazed gold bars. The fracture of the titanium specimens was ductile, with dimples occurring at the fracture surfaces. PMID- 2903609 TI - Immunocytochemical study of catecholaminergic innervation in the guinea pig cochlea. AB - The enzymes for synthesis of catecholamine, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyl transferase (PNMT), have been immunocytochemically localized in the guinea pig cochlea. Two groups of catecholamine-containing neurons could be distinguished. The first group, which was TH-positive/DBH, PNMT-negative, was found in the inner spiral bundle and the tunnel spiral bundle. The other group was TH, DBH-positive/PNMT-negative, and was found around the blood vessels. The immunocytochemical evidence obtained in this experiment suggests that the catecholamines should play a functional role in the guinea pig cochlea. PMID- 2903610 TI - [Effects of DL-demethylcoclaurine on experimental heart failure]. PMID- 2903611 TI - [Effects of nucleus raphe magnus and locus coeruleus in descending modulation of the habenula on pain threshold and acupuncture analgesia]. PMID- 2903612 TI - [Mechanism of hypotensive effects of verticillatine]. PMID- 2903613 TI - [Characterization of prostaglandin E2 receptors in the lung of guinea pigs]. PMID- 2903614 TI - Ontogeny of the dopamine and cyclic adenosine-3':5'-monophosphate-regulated phosphoprotein (DARPP-32) in the pre- and postnatal mouse central nervous system. AB - The ontogeny of a dopamine and cyclic adenosine-3':5'-monophosphate-regulated phosphoprotein with an apparent molecular weight of 32 kilodaltons (DARPP-32) has been studied in the central nervous system of the prenatal, newborn and adult mouse. DARPP-32-immunoreactive somata were first identified at day 12 of gestation, in the primary olfactory cortex and in the ventrolateral medulla oblongata. On day 14 of gestation, neurons containing DARPP-32-like immunoreactivity became apparent in the caudate nucleus, olfactory tubercle, nucleus accumbens, frontoparietal cortex and the ventral medulla oblongata. During the period up to and including birth, the number of cell bodies and fibres in all these areas increased markedly. In addition, DARPP-32-positive neurons became visible in the olfactory nucleus, the arcuate nucleus, and DARPP-32 positive cells appeared in the choroid plexus of the lateral, third and fourth ventricles. DARPP-32-containing fibres could be seen in the median eminence, the ventrolateral thalamus, and in the striatonigral projection, descending in the internal capsule to ramify extensively in the substantia nigra. Only in the cerebellum and suprachiasmatic nucleus did the development of DARPP-32-like immunoreactivity occur postnatally. The development of tyrosine hydroxylase, the rate-limiting enzyme for catecholamine synthesis, was simultaneously examined. The arrival of the tyrosine hydroxylase-containing projection to the caudate nucleus, the olfactory tubercle and the nucleus accumbens apparently occurred 1-2 days after the appearance of DARPP-32-immunoreactive cells within these regions. In the ventral and ventrolateral medulla oblongata, and the primary olfactory cortex, no tyrosine hydroxylase innervation was seen near the DARPP-32-positive neurons at days 12-14. The organization of the DARPP-32-containing somata of the caudate nucleus into aggregates of 5-15 neurons was partly paralleled spatially by an increased density of tyrosine hydroxylase-positive fibres. Many DARPP-32 immunoreactive cells in the immature mouse brain are present by the day of birth, particularly in the areas known to receive a dopaminergic innervation. The development of these presumptive dopaminoceptive DARPP-32-containing neurons does not seem to be dependent on the presence, however, of a dopaminergic input, since in all regions examined DARPP-32-LI preceded the appearance of tyrosine hydroxylase-like immunoreactivity by at least 1-2 days. Indeed, the results suggest that the existence of DARPP-32-like immunoreactivity in cell bodies and dendrites may be a pre-requisite for the formation or subsequent stabilization of dopaminergic synapses. PMID- 2903615 TI - Messenger RNAs of beta-amyloid precursor protein and prion protein are regulated by nerve growth factor in PC12 cells. AB - The effect of the neurotrophic factor NGF on the expression of two genes involved in the accumulation of amyloid deposits in neurodegenerative disorders was studied in a clonal cell line, PC12. Use of hybridization methods showed that NGF increased the cellular pool of the mRNA of the prion protein, a macromolecule known to generate fibrillary aggregates in the brain of scrapie-infected animals. Maximal levels of prion mRNA were obtained after 7 days of treatment, but a significant increase was already detectable after 48 hr of exposure to NGF. In contrast, the factor did not increase the cellular content of the transcripts coding for the precursor of the beta-amyloid peptide (APP), which participates in the formation of neuritic plaques in human brains affected by Alzheimer's disease. However, NGF caused a drop in the molecular weight of that mRNA. This change, which is likely to result from a loss of 100-200 bp, was already detected after 24 hr of treatment. These results indicate that NGF induces in target neuronal cells a quantitative and a qualitative modification of the transcription products encoding two different amyloid precursor proteins. PMID- 2903616 TI - Studies on posthypoglycemic insulin resistance in insulin-dependent diabetes mellitus. AB - Altogether 54 male patients with insulin-dependent diabetes mellitus participated in the studies. The impact of insulin-induced hypoglycemia on posthypoglycemic insulin sensitivity was evaluated for up to 12 hours following nadir hypoglycemia. The effect on glucose homeostasis following transient elevation of counterregulatory hormones was studied by exogenous administration of adrenaline, adreno-corticotropic hormone and growth hormone and by suppression of the endogenous release of growth hormone in connection with hypoglycemia. The studies were performed in the fasting state preceded by a 24 hour intravenous insulin infusion in order to avoid interference of subcutaneous insulin. Insulin resistance was determined by a constant rate intravenous infusion of somatostatin, insulin and glucose. This test seemed appropriate for the evaluation of total insulin resistance, and its reproducibility was acceptable. By using this method it was demonstrated that insulin resistance occurred for at least 12 hours after a hypoglycemic event in patients with IDDM, and that adrenaline caused immediate insulin resistance which, however, faded out within four to six hours, while GH exerted no immediate effect on insulin sensitivity but caused marked and sustained insulin resistance after a lag period of about four hours. Cortisol had no apparent effect within six hours but enhanced the effect of GH. The magnitude of these diabetogenic effects of hypoglycemia and GH was less pronounced in patients who already were more insulin resistant. These results are compatible with the idea that adrenaline is of major importance for the counterregulation and restoration of blood glucose during the first few hours following hypoglycemia, while GH is responsible for the induction of a long lasting state of insulin resistance. It is possible that such prolonged insulin resistance may cause posthypoglycemic hyperglycemia in patients with IDDM. These studies therefore indicate that the GH suppressing hormone somatostatin may be of clinical value as an adjunct to insulin in the treatment of patients with insulin dependent diabetes mellitus and labile blood glucose control. PMID- 2903617 TI - Nonhuman primate retrovirus isolates and AIDS. PMID- 2903619 TI - The clinical efficacy of sulphasalazine in rheumatic disease. PMID- 2903618 TI - Atropine and hexamethonium-sensitive, Ca/K-modulated, reversible swelling of mast cells in rat mesentery, due to feeding or exposure to carbachol. AB - Transitory swelling of mesenteric mast cells was observed when 24 h-fasted rats were given access to food. Atropine, an anti-muscarinic drug given (1 mg/kg, i.p.) 60 min prior to feeding, prevented this response; carbachol, a cholinomimetic drug caused it to occur when given (2 micrograms/kg, i.v., 10 min) to fasted rats. Mast cells in the mesentery excised from fasted rats, presented swelling in vitro within 1 min following exposure to 10(-7) M carbachol. This response was inhibited by atropine (10(-8) M) or hexamethonium (10(-8) M), indicating that stimulation of a parasympathetic nerve pathway, reported to exist in rat mesentery, could induce mast cell swelling. Exposure to a Ca2+ free medium also led to rapid swelling of mast cells in the mesentery excised from fasted rats. This result, as well as inhibition of the mast cell response to carbachol caused by increasing the Ca2+ (but not by increasing the Mg2+) content of the incubation medium, suggests that swelling was caused by a sudden decrease of Ca at mast cell membrane sites controlling ion/water fluxes. Mast cells swollen by feeding, carbachol or Ca-lack, reverted to their original condition within 20 min when incubated in balanced salt buffer. Such reversal did not occur in a KCl enriched medium. An equivalent (in terms of ionic strength), increase in NaCl, did not reproduce this effect, indicating that mast cells have K+-dependent means of compensating for endogenously or drug-induced volume changes. Swelling caused by cholinergic stimulation of mast cells was not accompanied by granule exocytosis.2+ carbachol-treated rat blood in vivo or in vitro, is discussed in terms of putative mast cell-controlled, localized homeostasis in the rat mesentery. PMID- 2903620 TI - [The effect of bunazosin hydrochloride on the intraocular pressure and the aqueous humor dynamics of the rabbit eye]. PMID- 2903621 TI - T lymphocyte subsets in Mediterranean spotted fever. AB - Several studies have previously suggested the possible role of a T lymphocyte suppressor population in infections by species of the genus Rickettsia. In 15 patients with Mediterranean spotted fever (MSF), we quantified, during the acute and convalescent phases of the disease, the peripheral blood lymphocyte populations using monoclonal antibodies that recognize CD3+, CD4+, CD8+, CD38+ and CD20+ cells. In three cases a reversal in the normal ratio of T lymphocyte helper-inducer/suppressor-cytotoxic subsets was detected lasting, in two of them, up to the fifth week of the disease. This disturbance was always weak and lacked clinical significance. PMID- 2903622 TI - Isolation of Theileria parva schizonts from infected lymphoblastoid cells. AB - This study set out to develop a rapid method for the isolation of schizonts from Theileria parva-infected bovine and buffalo lymphoblastoid cells. Parasitized lymphoblastoid cells were lysed by treatment with the cytolytic toxins, aerolysin and Ah-1 hemolysin, produced by Aeromonas hydrophila, and the schizonts were separated by Percoll density-gradient centrifugation. Light and electron microscopic examination showed that the isolated schizonts from lymphoblastoid cells infected with T. parva (Muguga) retained their normal morphology and were essentially free from host cell components. The schizonts also retained antigens as recognized by a series of anti-schizont monoclonal antibodies. The concentrations of toxin and Ficoll 400 in the lysis buffer which gave optimal cell lysis varied for 10 different infected cell lines tested. PMID- 2903623 TI - Plasma concentrations of sulfadoxine in healthy and malaria infected Thai subjects. AB - The disposition of sulfadoxine was studied in the presence of pyrimethamine in 18 healthy Thai subjects who had been suffering from falciparum malaria in the 6 months prior to the study, and in 12 Thai patients with acute malaria. The volunteers were administered an oral dose of 500 mg sulfadoxine + 25 mg pyrimethamine (1 Fansidar tablet). They were classified retrospectively as responders (Group I, n = 8) or nonresponders (Group II, n = 10) according to previous response to treatment with Fansidar. The patients were treated with 3 Fansidar tablets corresponding to 1500 mg sulfadoxine and 75 mg pyrimethamine. Five of them were completely cured. Seven patients showed R I or R II resistance. In all cases blood samples were collected up to 288 h post dose. The resultant plasma was analyzed for active (i.e. unchanged) and total sulfadoxine using a modified Bratton-Marshall method. In the healthy volunteers the plasma concentration time course of total sulfadoxine was similar for responding and nonresponding subjects. However, in nonresponders active sulfadoxine tended to show shorter half-lives (harmonic means were 212 h vs 267 h, respectively). Furthermore, significantly higher amounts of metabolites (mainly N4 acetylsulfadoxine) were present in plasma of nonresponders. In contrast to these findings, in malaria patients, plasma concentrations of active and total sulfadoxine were even higher in nonresponders as compared to the subjects who could be successfully cured. Furthermore, in this case there was no increase of the amount of metabolites in plasma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903624 TI - Trypanosome-induced ovarian dysfunction. Evidence of higher residual fertility in trypanotolerant small East African goats. AB - Changes in the length of oestrous cycles, plasma progesterone and oestradiol-17 beta levels were monitored for 6 months in Trypanosoma congolense-infected normocyclic small East African goats obtained from three tsetse-endemic areas and one tsetse-free area of East Africa. Irregular oestrous cycles were observed in all infected goats, before cessation at the second cycle post-infection in the more susceptible and fourth cycle in the more resistant goat groups. A significant decline in the progesterone and oestradiol-17 beta parameters were observed. The decline in hormonal values was, however, less in the more resistant than in the susceptible goat groups at least in the first 2 months post infection. Resumption of the ovarian cycle were observed in few resistant goats after 5 months of the infection. It is concluded that clinical tolerance is correlated with residual fertility, i.e., the greater the tolerance the higher the retention of fertility. PMID- 2903625 TI - Berenil (diminazene aceturate)-resistant Trypanosoma congolense in cattle under natural tsetse challenge at Kibaha, Tanzania. AB - Twenty-nine cattle, naturally infected with Trypanosoma congolense Kibaha, were subjected to chemotherapy with diminazene aceturate (Berenil, Hoechst) at 3.5 to 14.0 mg/kg. Fourteen animals recovered while six were refractory to treatment at 7.0 to 14.0 mg/kg. Further treatment of the Berenil-resistant isolates with isometamidium chloride (Samorin, May and Baker) at 1.0 mg/kg, effected cure. Corresponding chemotherapeutic trials in mice showed that the isolates were resistant to diminazene aceturate at 56.0 mg/kg and sensitive to Samorin at 20.0 mg/kg. It is noted, that T. congolense infections that do not respond to treatment with Berenil at 7.0 mg/kg may indicate development of resistance; the use of Samorin at 1.0 mg/kg or Homidium may be the alternative. The paper calls for judicious use of Berenil and Samorin, as they are the only sanative pairs available for the chemotherapy of bovine trypanosomiasis. PMID- 2903626 TI - Microfilaraemia, filarial antibody, antigen and immune complex levels in human filariasis before, during and after DEC therapy. A two-year follow-up. AB - A study on the effect of DEC therapy on microfilaraemia and the immune status in 27 patients with W. bancrofti infection was carried out for two years. Persistence of microfilaraemia was observed in 4 out of 27 cases after one course of DEC therapy and were treated again for one week. On further follow-up, none was microfilaraemic upto Day 60. The mean filarial antibody titres of IgM and IgG showed a gradual decrease as assessed by enzyme linked immunosorbent assay (ELISA). The mean titres of circulating microfilarial excretory-secretory (ES) antigens and immune complexes (ICs) showed an initial increase during therapy, followed by a gradual fall upto Day 60. Filarial antigen was detected in urine of all the carriers during therapy. Excretion pattern of antigen in urine showed correlation with DEC dose. Reappearance of microfilariae (mf) in circulation in 12 patients after a year showed that DEC had temporary attenuating effect on adult worms or no effect on developing larvae, suggesting further treatment and follow-up of patients. Parasitological and immunoscreening at the end of 2 years showed that the presence of mf ES antigen in blood correlated with the appearance of microfilariae in blood. PMID- 2903627 TI - Evaluation of skin biopsies from different body regions of onchocerciasis patients in Central Nigeria. AB - The diagnostic potential of skin snips from different body regions was evaluated in 97 onchocerciasis patients of Central Nigeria. Biopsies from the iliac crest had the greatest diagnostic potential followed by those of the calf and shoulder with 95% of Onchocerca volvulus carriers being diagnosed from these sites. However, 23.7% of microfilarial carriers in the skin of the outer canthus, shoulder, calf and ankle were negative in the iliac crest. The probability of diagnosing onchocerciasis in microfilarial positives from the 5 sites was, 0.76 for the iliac crest; 0.63 for the calf; 0.31 for the shoulder; 0.27 for the ankle; and 0.08 for the outer canthus. The concentrations of microfilariae in skin snips were significantly associated with the probability of a positive diagnosis especially with regard to those of the shoulder, iliac crest and calf. PMID- 2903629 TI - [Morbidity due to bilharziasis caused by S. haematobium. Relationship between the bladder lesions observed by ultrasonography and the cystoscopic and anatomo pathologic lesions]. AB - Twenty-seven patients with proved urinary schistosomiasis and echographic bladder lesions were selected for cystoscopic examination and biopsy. All patients had specific lesions at cystoscopic investigation. Histologic examination confirmed diagnosis 26/27 cases. Ultrasonography appears as a very efficient method for detection of schistosomiasis bladder pseudo-tumors. PMID- 2903628 TI - Liver involvement in human schistosomiasis mansoni. Regression of immunological and biochemical disease markers after specific treatment. AB - Peripheral blood cholyglycine and procollagen-III-peptide were measured in 22 Zairean patients with hepatomegaly caused by S. mansoni before and after treatment with praziquantel. Circulating T-cell subsets and cutaneous in vivo delayed type hypersensitivity were assessed; serum neopterin and beta 2 microglobulin served as indicators for macrophage/lymphocyte activation. The results were compared to age and sex matched patients with S. mansoni infection limited to the intestinal tract and schistosomiasis free controls with equal socioeconomic background. Abnormal serum cholyglycine and neopterin levels and alterations of circulating T-cell subset frequencies were associated with hepatomegaly in schistosomiasis. Normalization of these parameters reflected a regression of egg-induced immunopathology as early as two months after specific chemotherapy. Serum procollagen-III-peptide concentrations rose significantly after treatment, suggesting release of propeptide previously incorporated without cleavage into tissue collagen. The combination of these biochemical and immunological parameters may allow assessment of the pathophysiological mechanisms responsible for liver disease in individual patients. PMID- 2903630 TI - Inhibition of Plasmodium vinckei-malaria in mice by recombinant murine interferon gamma. PMID- 2903631 TI - Haemorrhagic syndrome associated with T. vivax infections of cattle in Somalia. PMID- 2903632 TI - Functional and structural analysis of the ribonucleoprotein complexes of different human influenza virus strains. AB - Ribonucleoprotein (RNP) cores were prepared from various strains of human influenza virus by treating the purified or spikeless virus particles with non ionic detergents such as Nonidet P-40 and centrifugation in continuous linear glycerol gradients. In addition to RNA, the purified complexes contained viral nucleoprotein (NP) and the three P proteins (PA, PB1, PB2) as determined by polyacrylamide gel electrophoresis (PAGE) under denaturing conditions. Contaminations with other viral polypeptides, especially HA1, HA2 and M were below 1%. All RNP complexes were transcriptionally active in vitro. Comparison of the polymerase activity of purified complexes revealed considerable differences depending not only on the content of polymerase proteins. The activity of RNP complexes was enhanced for all strains tested by adding of ApG. PMID- 2903633 TI - Antibodies to polymerase proteins of influenza virus A/PR/8/34 (H1N1): comparison on the immunoreactivity with polymerase proteins of other influenza A and B virus strains. AB - The polymerase proteins (PB1, PB2, PA) of the influenza virus strain A/PR/8/34 (H1N1) were isolated from whole virion or ribonucleoprotein (RNP) fractions by electrophoresis on polyacrylamide gel and electroelution or Sepharose CL-6B chromatography in the presence of SDS. Antisera to polymerase proteins (P proteins) were raised in rabbits; the immunoglobulins (Ig) were purified by affinity chromatography. Characterization of the antibody fraction by Western blot analysis showed a highly monospecific reaction with the three polymerase proteins. Spot immunobinding assay was used to compare the immunoreactivity of the monospecific polymerase antibodies with the P proteins of other influenza A subtypes and influenza B strains, revealing high immunoreactivity with the components of all influenza A strains and only insignificant reactivity with the components of the influenza B strains tested. PMID- 2903634 TI - Absence of cytomegalovirus, Epstein-Barr virus, and papillomavirus DNA from adenoma and adenocarcinoma of the colon. AB - Biopsy specimens from 13 patients with adenocarcinoma of the colon and from 10 patients with endoscopic polypectomies for colon adenoma were examined for the presence of the DNA of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human papillomavirus (HPV) types 2, 6, 16 and 18. The specific activities of viral DNA probes obtained by nick--translation ranged from 10(7) to 10(8) cpm/micrograms DNA. By Southern blot hybridization with an estimated sensitivity of 10 pg virus DNA which corresponded to 0.05 virus genome equivalents per cell we failed to detect any virus DNA in the biopsy material tested. PMID- 2903635 TI - Five year study of rotavirus gastroenteritis in Bulgaria. AB - We tested by electron microscopy 7,530 samples from children admitted to different hospitals in Sofia between February 1981 and February 1986; from these, rotaviruses were found in 725 (9.6%) faecal samples. Electron microscopic analysis of 264 samples from 181 children admitted to the hospital of infectious diseases in Shumen between December 1984 to February 1986 revealed rotaviruses in 120 (66.6%) of the tested children. A part of the samples positive by electron microscopy was tested by ELISA and polyacrylamide gel electrophoresis for rotavirus RNA segment patterns. Rotaviruses with eight different electropherotypes were found in Bulgaria. The seasonal culmination of the rotavirus gastroenteritis in the winter months has been confirmed. Rotavirus antibodies were found in 73% of the sera from 152 children tested. PMID- 2903636 TI - A simple novel procedure for preparation of herpes simplex virus subunit vaccine. AB - A simple procedure for preparation of herpes simplex virus type 1 (HSV-1) subunit vaccine is described. The method is based on treatment of virus-infected cells with a nonionic detergent, removal of cell nuclei by low speed centrifugation, separation of viral nucleocapsids by high speed centrifugation through a sucrose cushion and, finally, precipitation of viral and cellular glycoproteins and proteins with ammonium sulphate (AS). Unlike to acetone precipitation, affinity chromatography on lectins or hydroxylapatite chromatography, AS precipitation repeatedly yielded the best and most reliable results as judged by relative protein content, antigenicity and immunogenicity of the final vaccine product. PMID- 2903637 TI - Purification of murine alpha-herpesvirus and some properties of its DNA. AB - Strain Sumava Af of murine alpha-herpesvirus (MHV) banded in density gradient at the boundary between 10-20% and 20-30% Ficoll solution. In electron microscope, the partially purified virus visualized by negative staining exhibited intact or disrupted envelope structures and capsid particles of about 110 nm in outer diameter. The DNA extracted from partially purified virus and further purified in CsCl density gradient had the Tm-value of 79.0 degrees C. The molecular weight of about 90 million daltons was calculated for viral DNA according to its migration in agarose gel. PMID- 2903638 TI - Monoclonal antibodies neutralizing the antiviral and the antiproliferative activities of human interferon gamma. AB - Spleen cells from BALB/c mice immunized with human leukocyte interferon gamma (HuIFN-gamma) were fused with mouse NSO myeloma cells. Nine hybridoma lines were found secreting monoclonal antibodies (MoAb) which were able to neutralize the antiviral activity of HuIFN-gamma. All nine MoAb inhibited also the antiproliferative activity of HuIFN-gamma. The ability of tested MoAb to inhibit both the antiviral and antiproliferative activities of HuIFN-gamma supports the suggestion that a common domain on HuIFN-gamma molecule might be responsible for both biological activities. However, ELISA and/or RIA proved unsuitable for detection of these specific MoAb. PMID- 2903639 TI - Epstein-Barr virus (EBV) antibodies in children with non-Hodgkin's lymphomas. AB - Antibody titres against Epstein-Barr virus (EBV) antigens in children suffering from non-Hodgkin's lymphoma (NHL) were determined. IgG antibody titres against the viral capsid antigen (VCA) and early antigen (EA) exceeded those found in healthy control subjects. On the other hand, antibody titres against EBV determined nuclear antigen (EBNA complex) were generally lower than in the control group. The most striking phenomenon observed in the patient group was the frequent activation of latent virus infection as revealed by the periodical appearance of anti-EA and IgM class anti-VCA antibodies. Antibody titres against EBV antigens were generally lower among patients with progressing disease than in those with a more favourable course of the illness. The closest relation to EBV based on serological findings, was detected in lymphoblastic lymphomas of Burkitt type histology, poorly differentiated lymphocytic lymphomas, and in lymphomas localized in the abdomen. The question whether EBV might be involved in a certain proportion of the cases examined is discussed and further approaches to elucidate this problem are suggested. PMID- 2903640 TI - Unchanged expression of Epstein-Barr virus-determined nuclear antigen-1 in productive virus cycle. AB - The level of the Epstein-Barr virus (EBV)-determined nuclear antigen (EBNA-1) encoded by the Bam HI-K fragment of EBV DNA remained unchanged in P3HR-1 cells after induction of the productive cycle of virus replication by sodium-n-butyrate and 12-o-tetradecanoylphorbol-13-acetate (TPA). This was shown by the same capacity of cell-free extracts from untreated and treated P3HR-1 cells to absorb anti-EBNA-1 antibody from a known human serum. PMID- 2903641 TI - Concentration and purification of Newcastle disease virus by microfiltration and exclusion liquid chromatography. AB - Newcastle disease virus (NDV) was concentrated and purified by microfiltration and exclusion liquid chromatography (ELC) on macroporous glass (MPG). The purified NDV eluted as one peak; its yield was strain-dependent, the degree of purification was 95% to 99%. PMID- 2903642 TI - Immunity in Q fever. AB - Post-infection and post-vaccination immune mechanisms in Q fever are summarized. Whereas cell-mediated immunity has been found to play a crucial role in developing resistance to Coxiella burnetii infection, data on the role of specific antibodies in Q fever immunity are controversial. The functional state of immunocompetent cells and professional phagocytes seems to be decisive for the persistence of C. burnetii within phagocytic cells and for the control of Q fever at the host level. Defects of cellular immunity, immune complex formation, and immune response modulation by C. burnetii isolates differing in plasmid composition or LPS antigenic structure are implicated as aetiological factors. Immunogenicity and reactogenicity of three possible vaccine candidates (phase I chloroform-methanol treated and untreated corpuscular vaccine, and phase I soluble chemovaccine) for Q fever prophylaxis is discussed, stressing the need for developing suitable models and defined experimental conditions enabling to compare and evaluate the results obtained in different laboratories. PMID- 2903643 TI - The role of imaging in the management of the impalpable undescended testis. PMID- 2903644 TI - Treatment of reactions to contrast media. PMID- 2903645 TI - Successful treatment of angina pectoris with liver transplantation and bilateral internal mammary bypass graft surgery in familial hypercholesterolemia. PMID- 2903646 TI - Celiprolol: introduction. PMID- 2903647 TI - Proceedings of a symposium. Beta-blockers: perspectives beyond cardioselectivity. An official satellite to the second Cardiovascular Pharmacotherapy International Symposium. San Francisco, California, October 21, 1987. PMID- 2903648 TI - The role of adrenoceptors in circulatory and metabolic regulation. AB - This survey covers the classification and subdivisions of alpha- and beta adrenoceptors, including alpha 1 and alpha 2, beta 1 and beta 2, and pre-and postsynaptic receptor subtypes, together with the distribution and functional relevance of the various adrenoceptor subtypes. The emphasis will be on their relevance in circulatory regulatory processes, especially those of the blood vessels. The alpha- and beta-adrenoceptor antagonists that interact with various receptor subtypes are briefly discussed. The control of alpha 2-adrenoceptors concerned with blood pressure regulation is an important target for centrally acting antihypertensive drugs (such as clonidine or alpha-methyldopa). Changes in adrenoceptor density, particularly the down-regulation of beta 1- adrenoceptors (but not beta 2), are found in congestive heart failure. However, the experimental findings about alpha-and beta-adrenoceptors in essential hypertension remain controversial. Finally, the influence of alpha- and beta adrenoceptor antagonists on plasma lipids and carbohydrate metabolism is briefly reviewed. The changes found may be only partly explained on the basis of alpha- or beta-receptor blockade. PMID- 2903649 TI - Circulatory and metabolic aspects of beta-adrenoceptor blockade. AB - beta-Blocking therapy is used extensively is conditions as diverse as hypertension, angina pectoris, arrhythmias, thyrotoxicosis, hypertrophic cardiomyopathy, migraine, glaucoma, and myocardial infarction. Studies show they beneficially influence sinus node and atrioventricular conduction, but excessively high doses may cause sinus arrest or sinoatrial block. Nonselective beta-blockade in asthmatic patients may aggravate bronchoconstriction, whereas increased airways resistance is less likely with beta 1-selective, partial agonist, or alpha-beta-blocking drugs. Hypoglycemia can be prolonged; beta 1 selective or partial agonist drugs may cause less interference with glucose metabolism. beta-Blockade affects free fatty acids, lipids and lipoproteins, thyroid hormones, and parathormone. beta-Blockade may normalize abnormal platelet aggregation. Finally, the choice of the most effective drug depends on the clinician's knowledge of the various pharmacodynamic and pharmacokinetic drug profiles, allied with familiarity of the patient's medical condition. PMID- 2903650 TI - Optimal features of a new beta-blocker. AB - Therapeutics involves the careful balance between treatment disadvantages and advantages--the so-called risk-benefit ratio. Even after 20 years beta-blockers must be selected carefully to suit the patient's needs. This review examines several problems associated with beta-blockade. Generally, beta1 cardioselectivity is considered advantageous, but properties such as partial agonist activity, which limits receptor up-regulation, might be of greater value in reducing the adverse effects associated with abrupt drug withdrawal. Beta Blockers, either lipophilic or hydrophilic agents, have specific problems: lipophilic drugs provoke adverse central nervous system effects and need careful dose titration; variable gastrointestinal absorption is common with hydrophilic agents, whereas extra care is needed in patients with renal impairment. For most patients, especially those with asymptomatic conditions, once-daily dosing is preferred. For many, the quality of life is of overriding clinical importance. Despite significant pharmacokinetic and pharmacodynamic advances, the final criteria depend largely on a clinical assessment, improvement in the quality of life, and patient preference. We still await the discovery of an ideal beta adrenoceptor blocking agent; some of the newer beta-blockers, however have many of the properties that clinicians value. PMID- 2903651 TI - The central and peripheral hemodynamics of celiprolol. AB - The cardiovascular effects of celiprolol in healthy subjects and in those with cardiovascular disease and hypertension are reviewed. Unlike classic beta blockers, celiprolol does not depress cardiac contractility at rest while interfering to a lesser extent with cardiac function during exercise. Furthermore, celiprolol causes systemic vasodilatation, which, in hypertension, is mainly responsible for the blood pressure-reducing effects of the drug. Vasodilatation results from the reduction in vascular resistance of skeletal muscle tissues, but celiprolol also produces dilatation of vascular areas such as the kidney. This prevents a reduction in renal blood flow and consequently the salt and water retention associated with impaired perfusion. It is possible that such hemodynamic changes are dependent not on celiprolol's selective beta1 receptor-blocking properties but on certain additional properties. PMID- 2903652 TI - A long-term study of the effects of celiprolol on blood pressure and lipid associated risk factors. AB - In a 12-month study of 12 patients with essential hypertension treated with once daily celiprolol, 200 mg, mean supine blood pressure was reduced from 162/102 to 134/84 mm Hg (p less than 0.005)and standing pressures from 155/101 to 134/88 mm Hg (p less than 0.05). Similarly, heart rate fell from 83 to 71 beats/min in the supine position and from 90 to 79 beats/min in the standing position. Serum cholesterol level also fell from 5.35 to 4.78 mmol/L (p less than 0.01) and was accompanied by a nonsignificant loss of body weight. Lipid electrophoresis showed a nonsignificant increase in the high-density lipid fraction, from 1.2 to 1.7 mmol/L, and a significant decrease in the low-density lipid fraction, from 3.4 to 2.7 mmol/L (p less than 0.01). Serum triglyceride levels also decreased from 1.85 to 1.37 mmol/L (p less than 0.02), and low-density lipid-high-density lipid ratio fell from 3.29 to 2.03 (p less than 0.02). There was an unexpected reduction in serum fibrinogen levels, from 288 to 253 mg/dl (p less than 0.01). Aside from a slight reduction in the fasting blood glucose, there were no other significant changes in the urine or blood parameters, and no adverse drug effects occurred. It is likely that celiprolol's effect in reducing fibrinogen levels may minimize the increase in blood viscosity associated with the hypertensive state, whereas its effects on fibrinogen may herald a reduction in hypertensive complications such as thrombosis or retinal "cotton wool exudates." This warrants further investigation." PMID- 2903653 TI - Celiprolol in angina pectoris. AB - Celiprolol, a long-acting beta1-selective adrenergic-blocking drug with peripheral beta2-stimulatory and peripheral a2-inhibitory activities, has a unique vasodilator beta-blocker pharmacologic profile. The efficacy and safety of celiprolol in angina pectoris have been demonstrated in multiple studies that highlight its different hemodynamic properties compared with traditional beta blockers. Celiprolol was found to be an effective antianginal agent compared with placebo. In addition, in angina and ischemia its efficacy was comparable to that of propranolol and atenolol. PMID- 2903654 TI - Celiprolol in hypertension. AB - Celiprolol is a third-generation, beta-adrenoceptor antagonist with ancillary pharmacologic properties that are potentially advantageous in the treatment of hypertension. Celiprolol provides 24-hour control of blood pressure and in formal clinical trials has been found superior to a placebo and of equal efficacy to other commonly used beta-blocking drugs. It has also been found to be equally as effective as enalapril in lowering the resting blood pressure and superior in controlling the increases in blood pressure and heart rate during exercise. Celiprolol is known to exert a beneficial effect on the atheroprotective components of the risk factors for coronary heart disease, such as cholesterol triglyceride, and fibrinogen. Therefore the primary attributes of beta-blockade are uniquely advanced by celiprolol's ancillary pharmacologic activities. PMID- 2903655 TI - Improved left ventricular function during exercise: a comparison of celiprolol and atenolol. PMID- 2903657 TI - Safety profile of celiprolol. AB - Celiprolol hydrochloride is a highly cardioselective beta1-adrenergic antagonist with a unique pharmacologic profile. The adverse experience safety data derived from 18 double-blind trials (n = 2884) were evaluated. The results demonstrated a wide margin of safety for celiprolol over the recommended dosage range of 200 to 600 mg once daily. Celiprolol exhibited an adverse experience profile similar to that of placebo and resulted in a lower incidence of bradycardia and age associated increases in adverse event rates compared with atenolol and propranolol. PMID- 2903656 TI - Celiprolol and verapamil in the treatment of essential hypertension. PMID- 2903658 TI - A symposium: HMG CoA reductase inhibitors--a new therapeutic class. Atlanta, Georgia, March 26, 1988. Proceedings. PMID- 2903659 TI - Safety and efficacy of esmolol for unstable angina pectoris. AB - Esmolol is a rapidly metabolized cardioselective beta-adrenergic blocker that provides steady state beta-adrenergic blockade when administered by continuous intravenous infusion. To determine the efficacy of esmolol in the management of unstable angina, 23 patients with known coronary artery disease, who averaged 3.7 +/- 2.7 daily episodes of chest pain at rest, were randomized to receive either a continuous infusion of esmolol (n = 12) or oral propranolol (n = 11), as an adjunct to concomitant antianginal therapy. Patients with systolic blood pressure less than 110 mm Hg, heart rate less than 60 beats/min or known contraindications to beta blockade were excluded. Esmolol was titrated in a step-wise fashion from 2 to 24 mg/min at 5-minute intervals up to a 30% reduction in heart rate and systolic blood pressure double-product. The propranolol dose was increased every 6 hours by 50 to 100% to achieve a similar reduction in heart rate and blood pressure. When compared with their 24-hour baseline periods, both groups achieved a significant reduction in episodes of chest pain, from 4.6 +/- 3.3 to 1.4 +/- 1.5 in the esmolol group (p less than 0.02) and 2.6 +/- 1.4 to 1.0 +/- 1.5 in the propranolol group (p less than 0.02) during the subsequent study period. The cardiac event rate and incidence of drug side effects were similar between the 2 groups; however, side effects seen with esmolol did not require treatment after drug discontinuation. Thus, maximally tolerated beta blockade is an effective therapy for unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903660 TI - Incidence of gastrectomy in United States army hospitals worldwide from 1975 to 1985. AB - In the past 30 yr, hospitalization for peptic ulcer disease (PUD) has decreased. The use of total or partial gastrectomy to treat PUD has also declined. The discharge cover sheets of over 3000 patients who had a gastrectomy between 1975 and 1985 in U.S. Army hospitals were reviewed. PMID- 2903661 TI - Detection of submicroscopic deletions in band 17p13 in patients with the Miller Dieker syndrome. AB - The Miller-Dieker syndrome (MDS), a syndrome with lissencephaly, distinctive craniofacial features, growth impairment, and profound developmental failure, has been associated with a deletion of the distal part of chromosome band 17p13. A minority of patients with the syndrome do not have a deletion detectable with current cytogenetic techniques. Using three highly polymorphic DNA probes (pYNZ22, pYNH37.3, and p144D6) we have detected microdeletions in three MDS patients, two of whom had no visible abnormalities of chromosome 17. Loci defined by two of the DNA probes, pYNZ22 and pYNH37.3, were deleted in all three patients. The most distal locus, defined by p144D6, was present in one MDS patient, possibly defining the distal limits of the MDS region in band 17p13.3. None of these loci were absent in one case of lissencephaly without MDS. PMID- 2903662 TI - Normal human genomic restriction-fragment patterns and polymorphisms revealed by hybridization with the entire dystrophin cDNA. AB - Since the complete cDNA for the gene that causes X-linked recessive Duchenne/Becker muscular dystrophy (DMD/BMD) when mutated or deleted has recently been cloned and made generally available, DNA-based diagnostic studies of affected males and their families have entered into a new era. This communication sets forth the standard patterns of restriction fragments that are detected when normal human DNA cleaved with either HindIII or BglII is hybridized with seven contiguous segments comprising the entire 14-kb cDNA. Collectively, the more than 60 restriction fragments allow visualization of approximately 350 (HindIII) to 400 (BglII) kbp. This corresponds to the exon-containing one-fifth of the total genomic length of this gene, including the 3' untranslated region. Twelve two allele restriction-site polymorphisms that span the entire length of the gene were detected with the cDNA probes and allele frequencies determined. A diagnostic approach is proposed that starts with deletion screening of DNA from male probands, includes carrier detection based on relative fragment intensities, and extends to RFLP detection using the same autoradiographs prepared for deletion screening. Our results on deletion analysis of 32 DMD/BMD families are presented in an accompanying paper. PMID- 2903663 TI - Intragenic deletions in 21 Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) families studied with the dystrophin cDNA: location of breakpoints on HindIII and BglII exon-containing fragment maps, meiotic and mitotic origin of the mutations. AB - Following the strategy outlined in an accompanying paper, we studied 32 X-linked muscular dystrophy families (29 Duchenne [DMD] and three Becker [BMD] type) for abnormalities of HindIII and BglII fragments detected by the entire dystrophin cDNA. Twenty-one different single-intragenic deletions, and no duplications, were identified. The deletion endpoints were precisely mapped on the published HindIII fragment map. Detailed analysis of overlapping deletions led to clarification of the fragment order for some previously unsettled regions of the HindIII map and to the construction of a partial map of exon-containing BglII fragments. For the regions involved in deletions, the corresponding HindIII and BglIII fragments could be identified. Noncontiguous comigrating fragments were detected in two regions by careful analysis of the patterns in deletion patients. Four of the 21 deletions generated novel restriction fragments that facilitated detection of female carriers in these families. Twelve of the deletions had a breakpoint in one of the two large introns known to be the sites of breakpoint clusters. By combining deletions and RFLP analyses, we unequivocally identified the gamete that first carried the mutation in 13 families: eight oocytes and five sperm. Germ-line mosaicism previously detected in one male was confirmed by cDNA studies. In two additional families gonadal mosaicism was found in females. As evidence is accumulating for frequent mitotic origin of these deletion mutations, this phenomenon has to be considered when postulating mutational mechanisms and in genetic counseling of DMD/BMD families. PMID- 2903664 TI - Localization of the genetic defect in familial adenomatous polyposis within a small region of chromosome 5. AB - Familial adenomatous polyposis (FAP), a Mendelian disorder that includes familial polyposis coli (FPC) and Gardner syndrome (GS), has an autosomal dominant mode of inheritance. It is characterized by hundreds to thousands of adenomatous polyps that can progress to carcinoma of the colon, suggesting that the gene that harbors the FAP germ-line mutation may play an important role in the somatic genetic pathway to colon cancer. The defect responsible for FAP was recently mapped to the long arm of chromosome 5 by linkage between the FPC phenotype and a locus defined by DNA probe pC11p11 (D5S71), located at 5q21-22. Because an important next step in the paradigm for identification of a disease gene is to obtain a more precise localization, we isolated and mapped by linkage six additional polymorphic DNA markers in the FAP region. Subsequent linkage analysis in six pedigrees, three having the FPC phenotype and three segregating GS, placed the FAP locus very close to a new marker, YN5.48 (D5S81), that is approximately 17 centimorgans distal to C11p11 on the genetic map. The analysis revealed no evidence of genetic heterogeneity between the two phenotypes, a question that had not been clearly resolved by the earlier studies. The new set of markers in the near vicinity of the FAP locus represents a further step toward isolation of the genetic defect and provides the opportunity for preclinical diagnosis of risk status for colon cancer among individuals in families that are segregating adenomatous polyposis. PMID- 2903666 TI - Linkage studies in a large fragile X family. AB - We have analyzed the segregation of five loci in the region Xq27/28 in a large family affected by the fragile X syndrome. The marker DXS115 (767) is shown to be polymorphic with the enzyme PstI, as well as with BstXI. This marker will be useful in the analysis of both fragile X and haemophilia A families. The data presented here are consistent with the following order of loci: Xcen-F9 DXS105(cX55.7,55E)-DXS98(4D-8)- FRAXA-DXS52(St14)-DXS115(767)-qter. PMID- 2903665 TI - Identification and regional localization of DNA markers on chromosome 7 for the cloning of the cystic fibrosis gene. AB - To facilitate mapping of the cystic fibrosis locus (CF) and to isolate the corresponding gene, we have screened a flow-sorted chromosome 7-specific library for additional DNA markers in the 7q31-q32 region. Unique ("single-copy") DNA segments were selected from the library and used in hybridization analysis with a panel of somatic cell hybrids containing various portions of human chromosome 7 and patient cell lines with deletion of this chromosome. A total of 258 chromosome 7-specific single-copy DNA segments were identified, and most of them localized to subregions. Fifty three of these corresponded to DNA sequences in the 7q31-q32 region. Family and physical mapping studies showed that two of the DNA markers, D7S122 and D7S340, are in close linkage with CF. The data also showed that D7S122 and D7S340 map between MET and D7S8, the two genetic markers known to be on opposite sides of CF. The study thus reaffirms the general strategy in approaching a disease locus on the basis of chromosome location. PMID- 2903667 TI - Restriction analysis of the structural alpha-L-fucosidase gene and its linkage to fucosidosis. AB - Human alpha-L-fucosidase is a lysosomal enzyme responsible for hydrolysis of alpha-L-fucoside linkages in fucoglycoconjugates. A single gene, FUCA 1, located on chromosome 1p34.1-1p36.1 encodes for alpha-L-fucosidase activity. To gain insight into the nature of the molecular defects leading to fucosidosis, we have characterized the genomic structure of FUCA 1. Restriction-endonuclease analysis suggests that at least seven exons dispersed over 22 kb are present in genomic FUCA 1. Two restriction-fragment-length polymorphisms (RFLPs) have been identified in the Caucasian population. The PvuII and BglI RFLPs each have two codominant alleles in Hardy-Weinberg equilibrium. Allele frequencies for the PvuII RFLP are .70/.30, and those for the BglI RFLP .63/.37. Both RFLPs are in strong linkage disequilibrium with each other, with a correlation coefficient of .94. The polymorphism information content (PIC) of the combined DNA markers is .38, high enough to be useful in the prenatal diagnosis of fucosidosis. The combined lod score for linkage between the fucosidosis mutation and FUCA 1 markers in two families was significant at a recombination fraction of 0. This suggests that the fucosidosis mutation resides in FUCA 1. PMID- 2903669 TI - Collation of RFLP haplotypes at the human phenylalanine hydroxylase (PAH) locus. PMID- 2903668 TI - Identification of a mutation in the structural alpha-L-fucosidase gene in fucosidosis. AB - Fucosidosis is an autosomal recessive lysosomal storage disorder characterized by progressive neurological deterioration and mental retardation. The disease results from deficient activity of alpha-L-fucosidase (E.C.3.2.1.51), a lysosomal enzyme that hydrolyzes fucose from fucoglycoconjugates. In an attempt to identify the mutation(s) that result(s) in fucosidosis, we performed Southern blot analysis of the structural gene encoding alpha-L-fucosidase (FUCA 1) in 23 patients affected with fucosidosis. In five patients Southern blot analysis showed obliteration of an EcoRI restriction site in the open reading frame of FUCA 1 encoding mature alpha-L-fucosidase. This abnormality was not observed in 80 controls, and it may be the basic defect responsible for fucosidosis in these patients. Both patients with the severe type I form of fucosidosis and patients with the less severe type II were shown to be homozygous for this presumed mutation. In the remaining 18 patients the EcoRI site obliteration, major-gene deletions, or insertions were not detected. This suggests that at least two different mutations are involved in fucosidosis. The heterogeneity found at the DNA level was not present at the protein level, as all fucosidosis patients investigated had low fucosidase protein (less than 6% of normal) and negligible fucosidase activity in fibroblasts and lymphoblastoid cell lines. PMID- 2903670 TI - Benzodiazepine withdrawal. PMID- 2903671 TI - Severe Takayasu's arteritis in pregnancy: the role of central hemodynamic monitoring. AB - Maternal cardiovascular complications have been attributed to the dramatic hemodynamic changes associated with labor and delivery in patients with Takayasu's arteritis. The role of central hemodynamic monitoring in the management of a pregnant patient with severe Takayasu's arteritis is discussed. PMID- 2903672 TI - Endocrine responses of fetal lambs to hemorrhage after alpha 1-adrenergic receptor blockade. AB - To determine the importance of alpha 1-adrenergic receptors in the endocrine responses of fetal lambs to hemorrhage, eight chronically instrumented fetal lambs were bled of 20% of their measured blood volume after pretreatment with prazosin (24.8 +/- 2.1 days' gestation) or inert vehicle (124.2 +/- 2.2 days' gestation) according to a randomized, crossover protocol. Cortisol levels increased threefold with prazosin injection and remained elevated after hemorrhage but did not change with hemorrhage after vehicle infusion. Plasma renin activity was unaffected by the injection of prazosin but increased in both groups after hemorrhage. Vasopressin levels were unchanged in the control group throughout the experiment but increased tenfold with hemorrhage after pretreatment with prazosin. alpha 1-Adrenergic receptor blockade removes adrenergic inhibition of cortisol secretion and changes the hypotensive threshold for the secretion of vasopressin. PMID- 2903673 TI - Use of ophthalmic medications in pregnant and nursing women. PMID- 2903674 TI - Adrenergic blockade prevents endotoxin-induced increases in glucose metabolism. AB - Combined alpha- and beta-adrenergic blockade was used to investigate the role of catecholamines in endotoxin-induced elevations in glucose kinetics. Glucose kinetics were measured before and for 4 h after the injection of endotoxin [100 micrograms/100 g body wt iv, 30% lethal dose (LD30) at 24 h]. Adrenergic blockade was achieved by the bolus injection of phentolamine and propranolol followed by their continuous infusion. Endotoxin-treated rats exhibited a transient hyperglycemia and sustained (greater than 4 h) increase in plasma lactate concentration, as well as elevated rates of glucose appearance (Ra, 83%), disappearance (Rd, 58%), recycling (160%), and metabolic clearance (23%). Adrenergic blockade prevented endotoxin-induced increases in plasma glucose concentration, Ra, Rd, and recycling but not glucose clearance. The increase in plasma lactate concentration was blunted by 35%. After 2 h, endotoxic animals infused with adrenergic antagonists developed hypoglycemia, which may have resulted from an increased plasma insulin concentration. The attenuation of elevated glucose turnover by adrenergic blockade in the endotoxin-treated animals was not due to a reduction in plasma glucagon level or differences in plasma insulin concentration. Administration of the alpha- or beta-adrenergic antagonists separately blunted but did not prevent endotoxin-induced changes in glucose kinetics, and therefore the efficacy of the adrenergic blockade could not be assigned to a single receptor class. These results indicate that catecholamines are important contributory factors to many of the early alterations in carbohydrate metabolism observed during endotoxemia. PMID- 2903675 TI - Effect of methylene blue and N-ethylmaleimide on internal anal sphincter relaxation. AB - The present studies were performed in vitro to define the participation of regulatory cyclic nucleotides in the relaxation of internal anal sphincter (IAS) smooth muscle in response to neural stimulation by electrical field stimulation (EFS) vs. exogenous vasoactive intestinal peptide (VIP). EFS and VIP both caused relaxation of the resting tone in the opossum-isolated IAS smooth muscle strips. The addition of permeant cyclic nucleotide derivatives, the guanylate cyclase stimulant sodium nitroprusside (SNP), and the adenylate cyclase stimulant forskolin caused a dose-dependent fall in the resting tension of IAS smooth muscle. The inhibitory effect of the agonists on the IAS smooth muscle was not modified by tetrodotoxin (TTX), a neurotoxin. TTX almost abolished the IAS responses to EFS. The effects of SNP and forskolin were selectively blocked by the putative inhibitors of corresponding enzyme systems, i.e., methylene blue (MB) (3 X 10(-5) M) for guanylate cyclase and N-ethylmaleimide (NEM) (10(-4) M) in the case of adenylate cyclase. NEM and not MB caused significant antagonism of the fall in IAS tension in response to both EFS and VIP during the control experiments. Such data suggest a common biochemical link (adenosine 3',5'-cyclic monophosphate as second messenger system) between the IAS smooth muscle relaxations with neural stimulation and VIP. In addition, a part of the IAS smooth muscle relaxation in response to EFS also involves the mediation of guanosine 5'-cyclic monophosphate. PMID- 2903676 TI - Role of Ca2+ in bombesin-stimulated release of gastrin and somatostatin from isolated perfused rat stomach. AB - The role of calcium (Ca2+) in bombesin (BBS)-stimulated release of gastrin and somatostatin-like immunoreactivity (SLI) was examined in isolated perfused rat stomachs obtained from male rats fasted overnight. The stomachs were perfused via the celiac artery. BBS (1 nM) was perfused alone for 10 min or in combination with various Ca2+ antagonists, including 1) different doses of divalent cationic Ca2+ chelator (EGTA), 2) Ca2+ channel blockers (nifedipine, verapamil), and 3) calmodulin (Ca2+ binding protein) antagonist [trifluoperazine (TFP)]. The effluent was collected for measurement of gastrin and SLI. EGTA at doses of 2 or 5 mM blocked the BBS-mediated release of both gastrin and SLI. After removal of a low dose of EGTA from the perfusate, the release of both gastrin and SLI rebounded. On removal of a high dose of EGTA, however, SLI release remained depressed, but gastrin rebounded even more significantly. In the absence of BBS, the rebound of gastrin release was less dramatic, indicating that reexposure to Ca2+ partially contributed to the rebound phenomenon. Nifedipine (0.1-10 microM) markedly decreased BBS-stimulated release of gastrin and SLI in a dose-dependent fashion; the inhibitory effect of nifedipine on SLI release was significantly stronger than on gastrin release. Verapamil (10 microM) depressed BBS-induced SLI release but not gastrin release. TFP (50 or 100 microM) also resulted in inhibition of bombesin-elicited release of gastrin and SLI in a dose-related manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903677 TI - alpha-Adrenoceptors and cold-induced vasoconstriction in human finger skin. AB - Experiments were designed to determine how cold-induced vasoconstriction is mediated in superficial vessels of human finger skin. alpha-Adrenoceptor antagonists were administered into the finger skin by iontophoresis, and local cooling was applied by a laser-Doppler probe supplied with Peltier elements. Cold induced vasoconstriction was abolished after administration of the alpha 2 adrenoceptor antagonist rauwolscine but not after the alpha 1-adrenoceptor antagonist doxazosin. The results indicate that vasoconstriction on local cooling in human finger skin is mainly mediated by adrenoceptors of the alpha 2-subtype. PMID- 2903678 TI - Angiotensin receptor binding and pressor effects in cat subretrofacial nucleus. AB - Central administration of angiotensin II (ANG II) increases arterial blood pressure via increased sympathetic activity. We have examined the possibility that one site of action of ANG II is the subretrofacial (SRF) nucleus in the rostral ventrolateral medulla, since this nucleus is known to play a critical role in the tonic and phasic control of arterial pressure. In vitro autoradiography, employing 125I-labeled [Sar1, Ile8]ANG II as radioligand, was used to localize binding sites for ANG II in the cat ventrolateral medulla. A high density of ANG II-receptor binding sites was found confined to the SRF nucleus. In a second group of experiments in anesthetized cats, microinjections of ANG II, in doses ranging from 10 to 50 pmol, were made into histologically identified sites within and outside the SRF nucleus. Microinjections into the nucleus resulted in a dose-dependent increase in arterial pressure, which was abolished by systemic administration of the ganglion-blocking drug hexamethonium bromide. In contrast, microinjections just outside the SRF nucleus had no effect on arterial pressure. It is concluded that activation of ANG II-receptor binding sites within the SRF nucleus leads to an increase in arterial pressure via increased sympathetic efferent activity. PMID- 2903679 TI - Enhanced vascular alpha-adrenergic neuroeffector system in diabetes: importance of calcium. AB - Mesenteric arteries from streptozotocin (STZ)-diabetic rats developed greater contractile force in response to norepinephrine and related alpha-agonists than arteries from age-matched controls. Subsequent experiments attempted to define the mechanisms underlying these findings. Transmural nerve stimulation of mesenteric arteries from both groups of animals revealed a similar optimal frequency and voltage of stimulation; however, arteries from STZ-diabetic rats developed greater contractile force than controls. Second, determination of selective alpha-adrenergic antagonist affinities (pA2 values) revealed qualitatively similar postjunctional alpha 1-adrenoceptors in both groups of arteries. Third, disruption of the endothelium did not abolish the enhanced responsiveness of arteries from STZ-diabetic rats. In contrast, the increased vascular responsiveness in STZ-diabetes was associated with a greater dependency on extracellular calcium, with no change in the response to alpha-agonist-induced release of calcium from cellular stores. Thus the enhanced responsiveness of mesenteric arteries from STZ-diabetic rats to alpha-adrenergic agonists cannot be attributed to neuronal deterioration, altered postjunctional alpha-adrenoceptor subtypes, endothelium degeneration, or enhanced release of intracellular calcium but is associated with a greater dependency on extracellular calcium. PMID- 2903680 TI - Neurogenic and humoral factors maintaining arterial pressure in conscious dogs. AB - This study examined the contribution of each primary pressor system to resting arterial pressure and the ability of each to maintain pressure in the absence of the other systems in conscious dogs. In dogs with intact carotid sinus baroreflexes, ganglionic blockade (GB) reduced blood pressure by 13 +/- 3 mmHg, whereas blockade of the renin-angiotensin (RAS) and arginine vasopressin (AVP) systems did not significantly alter arterial pressure. After removal of the other two systems, the depressor response to blockade of the sympathetic nervous system (SNS) with hexamethonium and atropine was significantly augmented (-33 +/- 3 mmHg), whereas captopril (CAP) blockade of the RAS reduced pressure 14 +/- 4 mmHg, and AVP blockade decreased pressure 12 +/- 2 mmHg. In sinoaortic-denervated (SAD) dogs, the SNS exhibited a greater contribution (28 +/- 4 mmHg) to resting pressure compared with intact, and the role of the RAS (10 +/- 2 mmHg) was also augmented, whereas the effects of AVP blockade were unaltered. Effects of GB and CAP were unaltered after blockade of the other systems in SAD animals, whereas the depressor response to AVP antagonist (-13 +/- 2 mmHg) was significantly augmented. Results indicate the SNS is the primary pressor system in resting intact or SAD conscious dogs, whereas the RAS also contributes to resting blood pressure in SAD animals. The ability of the SNS alone to maintain arterial pressure after acute removal of the other systems is also significantly greater than that of AVP or the RAS. PMID- 2903681 TI - Biosynthetic capacity of hummingbird liver. AB - Hummingbirds have one of the highest mass-specific metabolic rates among vertebrate animals. High activities of pyruvate carboxylase (an enzyme involved in gluconeogenesis) and acetyl-CoA carboxylase (an enzyme involved in fatty acid synthesis) in hummingbird liver indicate that biosynthetic capacity is adjusted to cope with the high metabolic fuel requirements imposed by small size and hovering flight. This high biosynthetic capacity is supported by a correspondingly high oxidative capacity, as judged qualitatively by the abundance of mitochondria in electron micrographs and quantitatively by the presence of high citrate synthase activity (a Krebs cycle enzyme). To support their high metabolic fuel requirements, hummingbirds may possess the most biosynthetically active livers in nature. PMID- 2903682 TI - Pressor responses from electrical or glutamate stimulations of the dorsal or ventrolateral medulla. AB - In rats, rabbits, and cats anesthetized with alpha-chloralose and urethan, responses of the pressor areas of the dorsal portion (DM) and ventrolateral portion (VLM) of medulla and pons were compared. Electrical stimulation (monopolar square-wave pulses) on monosodium glutamate solution (Glu, 100-200 nl, 1 M) was delivered through an electrode-needle tubing connected to a Hamilton syringe for semimicroinjection. In all three of these species, pressor responses were elicited from both DM and VLM by either Glu or electrical stimulation. The most active parts of DM were found in the dorsomedial reticular formation of the rostral medulla to mid-medulla. In the pons and caudal medulla, the Glu-induced response was mild, although the electrically induced response was marked. Application of kainic acid (KA) to either DM or VLM produced an initial pressor response but was followed by a reduction of the pressure rise on subsequent electrical stimulation. Glu, unlike electrical stimulation, excites neural perikarya, not fibers of passage. KA initially excites the neural perikarya before causing damage that spares axons. These results thus suggest that both DM and VLM contain neural perikarya that mediate pressor effects. PMID- 2903683 TI - Acetyl-CoA hydrolase: relation between activity and cholesterol metabolism in rat. AB - To examine whether cytosolic acetyl-CoA hydrolase in rat liver is involved in regulation of cholesterol biosynthesis, we investigated the alteration of the enzyme activity under conditions of stimulation (cholestyramine treatment) and suppression [cholesterol feeding, a potent competitive inhibitor of microsomal 3 hydroxy-3-methylglutaryl-CoA reductase (CS 514) treatment, and a hypolipidemic drug [alpha-(p-chlorophenoxy)isobutyric acid, CPIB] injection) of cholesterol biosynthesis. The enzyme activity in rat liver increased significantly in the early diabetic, cholesterol-fed, CS 514-, and CPIB-treated groups, but no change in its activity was observed in chronic diabetic groups. Cholestyramine treatment to cholesterol-fed rats made the enzyme activity return to the initial level. When chronic diabetic rats were given a cholesterol diet or treated with CS 514 or CPIB, the activity increased significantly. Inhibition of cholesterol biosynthesis caused by these treatments induced increase in the enzyme activity with increase in the enzyme protein, judging from results obtained by enzyme linked immunosorbent assay. These results suggest that this enzyme has a physiological role in maintenance of the equilibrium between the cytosolic acetyl CoA concentration and CoA-SH pool for cholesterol metabolism. PMID- 2903684 TI - Effects of chronic sinoaortic denervation on central vasopressin and catecholamine systems. AB - The objective of this study was to determine whether chronic arterial baroreceptor deficit induces time-related changes in central vasopressin (AVP) and catecholamine systems. Groups of sinoaortic-denervated (SAD) and sham operated (SO) rats were studied 1, 3, 4, 7, and 14 days after surgery. Supraoptic (SON), paraventricular (PVN) and arcuate (ARC) nuclei, median eminence (ME) region, and A1 region of medulla were obtained by micropunch from frozen brain sections and assayed for AVP, tyrosine hydroxylase (TH) activity, catecholamines, and their metabolites, dihydroxyphenylethyleneglycol (DOPEG) and 2,5 dihydroxyphenylacetic acid (DOPAC). AVP concentration in SON and PVN was increased in 1-day-SAD rats, reduced in 3- and 4-day-SAD rats, equal and above control values in 7- and 14-day-SAD rats, respectively. TH activity was increased in SON and reduced in ME and ARC of 1- and 7-day-SAD rats. In SON, DOPEG was increased, whereas in ME all catecholamines and DOPEG and DOPAC were reduced in 1 day-SAD rats. ME catecholamines returned toward control levels in 3- to 4-day-SAD rats. These studies show that the chronic absence of arterial baroreceptor input produces time-related, regionally specific central changes of vasopressin and regionally associated catecholamines. PMID- 2903685 TI - Sleep disorders in the elderly. AB - In their own practices and in consultation, requests to psychiatrists to evaluate and treat sleep disorders in the elderly are common. The five million elders in this country receive 35%-40% of the sedative-hypnotics prescribed, despite the fact that they represent only 12% of the population. Since their sleep disturbances are usually secondary to medical, psychiatric, pharmacologic, or environmental causes, they should receive a thorough evaluation and differential diagnostic approach. Before prescribing a sedative-hypnotic, one should consider nonpharmacologic interventions and education about normal sleep changes due to aging. As a foundation for the judicious prescribing of sedative-hypnotics, the pharmacokinetic changes associated with aging are discussed. PMID- 2903686 TI - Higher frequency of neuroleptic-induced dystonia in mania than in schizophrenia. AB - In a study of 135 schizophrenic and 46 manic male patients treated with neuroleptics, a significantly higher proportion of the manic patients (26.1%) than of the schizophrenic patients (5.9%) developed acute dystonia. This suggests a higher vulnerability to acute extrapyramidal symptoms in mania. PMID- 2903687 TI - Cold agglutinin titers in psychiatric patients. AB - Cold agglutinin titers were obtained from the serum of 41 psychiatric patients. The 21 chronic schizophrenic patients tended to have positive cold agglutinin titers; the authors suggest that this immunological finding may be associated with long-term neuroleptic treatment. PMID- 2903688 TI - Beta blockers for treatment of priapism associated with use of neuroleptics. PMID- 2903689 TI - Invasive amebiasis in naturally infected New World and Old World monkeys with and without clinical disease. AB - Histopathological preparations of cecum and colon from monkeys naturally infected with invasive Entamoeba histolytica were examined to determine the distribution of amebae in the tissues and the types of lesions, if any, associated with them. Infections were studied in 3 New World species (10 Callicebus moloch, 1 C. torquatus, and 2 Aotus trivirgatus) and 3 Old World species (8 Macaca mulatta, 6 Erythrocebus patas, and 1 Cercopithecus aethiops). Amebiasis was recorded as the principal or a contributing cause of death of all of the 13 New World monkeys and in 6 of the 15 Old World monkeys; amebiasis was detected in the rest of the monkeys only after tissues were re-examined specifically for amebae. Amebae causing no apparent damage were found in the lamina propriae, mainly at the muscularis mucosae. Most frequent were colonies or aggregates of amebae in the crypts between the epithelium and basement membrane, causing either no evident necrosis or changes ranging from necrosis and disarrangement of adjacent cells to complete destruction of the epithelium and reduction of the cells to pyknotic bodies. A lesion interpreted as possibly characteristic of carrier-state invasive amebiasis was destruction of the epithelium in patches of mucosal crypts, not leading to ulceration. Uncommon but present in both New and Old World monkeys were typical areas of surface erosion and classical flask-shaped ulcers. The observations show that in some species of Old World monkeys amebiasis can be invasive without causing clinical disease. PMID- 2903690 TI - Brus Laguna virus, a Gamboa bunyavirus from Aedeomyia squamipennis collected in Honduras. AB - A virus isolate from Aedeomyia squamipennis collected in Honduras in 1967 was identified as a member of the Gamboa serogroup (family Bunyaviridae, genus Bunyavirus). This is the ninth Gamboa serogroup virus and the eighth shown to be a distinct serotype. PMID- 2903692 TI - [Protracted action of vecuronium in a patient with chronic renal insufficiency treated by dialysis]. AB - Although the pharmacokinetics of vecuronium are altered by the loss of kidney function, they do not differ significantly between patients with normal renal function and patients with renal failure. Therefore, the drug has become a preferred neuromuscular blocking agent in anuric patients. The author observed complete relaxation--verified by nerve stimulation--for more than 3 h following a single dose of 0.09 mg/kg vecuronium in a patient with chronic renal failure. Liver function was normal, and no drugs known to interact with vecuronium were used. The authors conclude that the altered pharmacokinetics of vecuronium in anuric patients might cause clinically significant effects in some patients. PMID- 2903691 TI - Changes in carbohydrate-deficient transferrin levels after alcohol withdrawal. AB - Sequential serum levels of carbohydrate-deficient transferrin (CDT) were determined in 72 alcoholics at various intervals during detoxification. Before treatment, 57 patients (79%) had increased CDT values (Group A), whereas in 15 individuals (21%) (Group B), CDT levels were within the normal range. In 51 Group A patients, CDT decreased progressively after cessation of alcohol intake (half life, 16 +/- 5 days), but fluctuated and remained abnormal in the remaining six. Nine Group B patients maintained normal CDT values throughout the follow-up period, but slightly or moderately increased levels were recorded on one occasion in the other six Group B subjects. Patients whose CDT levels had reached normal values after treatment, showed a recurrent increase in CDT after a relapse. gamma Glutamyl transferase activities, which were elevated in 56% of Group A and in 80% of Group B alcoholics, showed a decrease after cessation of alcohol consumption in most patients with initially elevated values (Group A, 30 of 32; Group B, 10 of 12). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, as well as mean corpuscular volumes (MCV) were normal in the majority of patients. CDT/total transferrin ratios correlated positively with CDT levels. CDT proved to be the most sensitive marker for chronic alcoholism (79%), whereas GGT activity levels were more useful only in patients with normal CDT levels before alcohol withdrawal. In the assessment of treatment outcome, the combination of CDT and GGT as markers yielded a sensitivity of 95%. PMID- 2903693 TI - Anaphylaxis following vecuronium. PMID- 2903694 TI - Haplotype analysis of the human beta-globin gene complex using multiple locus specific oligonucleotide probes. AB - Three oligonucleotide probes complementary to specific DNA sequences of the six human globin genes (epsilon, G gamma, A gamma, psi beta, delta, beta) were synthesized. The oligonucleotides were used either singly or in combination as hybridization probes to determine the haplotype of the human beta-globin gene cluster employing the four conventionally used restriction endonucleases HincII, HindIII, AvaII, and BamHI, in addition to HpaI. Polymorphism in the epsilon- and psi beta-genes (HincII) can be simultaneously determined with a single probe mixture. One of the probes complementary to both the psi beta- and gamma-genes is useful for determining both HindIII and HincII polymorphisms. The advantages of these probes relative to conventional cDNA probes are discussed. PMID- 2903695 TI - Electrochemical determination of arylsulfatase activity using high-performance liquid chromatography. AB - A highly sensitive assay for arylsulfatase A was developed using high-performance liquid chromatography with electrochemical detection. The retention time of the enzymatic product, p-nitrocatechol, on a reverse phase column was approximately 2.0 min. The assay was able to detect 0.43 pmol p-nitrocatechol in a 20 microliter ethanol extract of the reaction mixture. The coefficients of variation for seven determinations of the intra- and interassays were 9 and 8%, respectively. The levels of arylsulfatase A activity in human saliva samples and leukocyte and platelet lysates determined by this assay were within 6 and 11%, respectively, of the levels determined by a spectrophotometric assay. The high performance liquid chromatography assay may have utility in measuring arylsulfatase A activity in biological samples with low activity or specific activity or in samples with compounds which interfere with the spectrophotometric assay. PMID- 2903696 TI - Purification and characterization of low-molecular-weight beef heart proteolipids: use of fast atom bombardment-mass spectrometry for identification. AB - Bovine cardiac muscle was extracted by an acidic chloroform/methanol mixture. A combination of gel permeation and ion-exchange chromatographies in organic solvents and HPLC allowed the purification of subunits VIIIa (Mr 5400) and VIIIb (Mr 4900) of cytochrome c oxidase and of A6L protein (Mr 7900) of ATP synthase. The identification of the proteins was made possible by measurement of their molecular weight by fast atom bombardment-mass spectrometry (FAB-MS) in conjunction with conventional Edman degradation. The determination by FAB-MS of the molecular weight of A6L protein confirmed its supposed formylated N-terminal methionine. PMID- 2903698 TI - Immunocytochemical and electronmicroscopical data on the differentiation of somatostatin-containing endocrine cells in human large intestine. AB - The distribution and ultrastructure of the somatostatin-containing endocrine cells in the distal large intestine of fetuses, children and adults was investigated by silver impregnation, immunocytochemical and electron microscopical techniques. Somatostatin-containing endocrine cells in 10-14-week old fetuses were found to differentiate very intensively. In 19-25-week-old fetuses the frequency of occurrence began to decrease and this tendency was preserved during the subsequent stages of ontogenesis. Conversely, the frequency of occurrence of argyrophil endocrine cells increased. The change in the mean diameters of the secretory granules was also studied. PMID- 2903697 TI - Protein chemistry of the Neurospora crassa plasma membrane H+-ATPase. AB - A highly effective procedure for fragmenting the Neurospora crassa plasma membrane H+-ATPase and purifying the resulting peptides is described. The enzyme is cleaved with trypsin to form a limit digest containing both hydrophobic and hydrophilic peptides, and the hydrophobic and hydrophilic peptides are then separated by extraction with an aqueous ammonium bicarbonate solution. The hydrophilic peptides are fractionated by Sephadex G-25 column chromatography into three pools, and the individual peptides in each pool are purified by high performance liquid chromatography. The hydrophobic peptides are dissolved in neat trifluoroacetic acid (TFA), diluted with chloroform-methanol (1:1), and the hydrophobic peptide solution thus obtained is then fractionated by Sephadex LH-60 column chromatography in chloroform-methanol (1:1) containing 0.1% TFA. The recoveries in all of the above procedures are greater than 90%. The N-terminal amino acid sequences of three of the hydrophobic H+-ATPase peptides purified by this methodology have been determined, which establishes the position of these peptides in the 100,000 Da polypeptide chain by reference to the published gene sequence, and documents the sequencability of the hydrophobic peptides purified in this way. This methodology should facilitate the identification of a variety of amino acid residues important for the structure and function of the H+-ATPase molecule. Moreover, the overall strategy for working with the protein chemistry of the H+-ATPase should be applicable to other amphiphilic integral membrane proteins as well. PMID- 2903699 TI - Microtubule-granule relationships in motile human polymorphonuclear leukocytes. AB - We examined the relationship of microtubules to the granule organization in stimulated human polymorphonuclear leukocytes (PMNs). Electron microscopic (EM) observations of critical-point-dried PMNs revealed that only a portion of the granules appeared in close association to microtubules. These closely associated granules appeared to be attached to the microtubule via smaller-diameter filaments. The remaining granules appeared either attached to microtubules at a further distance, via smaller-diameter filaments such as actin, or unassociated with microtubules. EM observations of PMNs treated with either the microtubule promoter drug taxol or the microtubule depolymerization drugs nocodozole and colchicine revealed a redistribution of granules towards the nucleus. Granule clustering at the periphery of the cell was also noted with nocodozole and colchicine. With cytochalasin B, a uniform distribution of granules was noted. However, granule clustering was noted when PMNs were coincubated with cytochalasin B and colchicine. These results indicate that microtubules may have both a direct and indirect role (through other cytoskeletal elements) in the organization of PMN granules. PMID- 2903700 TI - Use of esmolol in the intraoperative management of pheochromocytoma. PMID- 2903701 TI - Actions of enflurane, isoflurane, vecuronium, atracurium, and pancuronium on pulmonary resistance in dogs. AB - The effects of enflurane, isoflurane, vecuronium, atracurium, and pancuronium on pulmonary resistance and heart rate were studied in 30 vagotomized dogs lying supine and anesthetized with chloralose-urethane. None of the five drugs affected pulmonary resistance when the airway was unstimulated. Enflurane and isoflurane significantly attenuated the increase in pulmonary resistance induced by electrical stimulation of the vagus nerves. This effect was dose-dependent and similar for both anesthetics at equivalent multiples of their minimum alveolar concentration. Atracurium significantly (P less than 0.05) enhanced the increase in pulmonary resistance induced by vagus nerve stimulation; vecuronium had no significant effect. Pancuronium, up to a cumulative dose of 0.14 mg/kg, also significantly (P less than 0.05) enhanced the increase in pulmonary resistance induced by vagus nerve stimulation; but this effect was reversed by further increasing the dose. Pancuronium also attenuated the cardiodecelerator response to vagus nerve stimulation in a dose-dependent fashion. The underlying mechanisms for the attenuation of responses to vagus nerve stimulation by enflurane or isoflurane or for the increase in response with atracurium are unknown. Pancuronium at lower doses increases the response most likely by blocking prejunctional muscarinic receptors (M2) that physiologically inhibit vagally mediated increases in pulmonary resistance. PMID- 2903702 TI - Transplacental passage and hemodynamic effects of esmolol in the gravid ewe. AB - Using a chronic maternal-fetal sheep preparation, the authors determined the transplacental passage and the hemodynamic changes consequent to maternal administration of esmolol. Fifteen experiments were performed in six chronically instrumented pregnant ewes near term. Each animal received esmolol iv, 500 micrograms.kg-1.min-1, for 4 min and then 300 micrograms.kg-1.min-1 for 6 min. Maternal and fetal blood esmolol concentrations (mean +/- SEM) were 1.2 +/- 0.28 and 0.1 +/- 0.03 micrograms/ml, respectively, at the completion of the infusion, and 0.03 +/- 0.01 microgram/ml in the mother and not detectable in the fetus 10 min after stopping the infusion. Despite the relatively low blood esmolol concentration in the fetus compared to the mother, the hemodynamic effects in the fetus were similar to those in the mother. The maximal decrease of maternal mean arterial pressure (MAP) and heart rate (HR) were 7 +/- 2 and 14 +/- 3% (mean +/- SEM), respectively (P less than .05). The maximal decrease of fetal MAP and HR were 7 +/- 2 and 12 +/- 3%, respectively (P less than .05). No changes were seen in maternal or fetal acid-base variables, and intra-amniotic pressure was not affected. The authors conclude that esmolol has a rapid but relatively small transplacental passage, and it is eliminated rapidly from both maternal and fetal plasma. PMID- 2903703 TI - Spinal administration of somatostatin in animals and humans. PMID- 2903704 TI - [Genetic counseling in ornithine carbamoyltransferase deficiency]. AB - Ornithine transcarbamylase (OTC) deficiency is an inborn error of urea cycle metabolism, responsible for lethal hyperammonemia in males and for severe symptoms in at least 20% of heterozygous females. The authors provide here additional data on the informativity of the protein loading test (PLT) for the detection of heterozygotes. They show that the risk of being a carrier for the mother of an affected boy falls from 2/3 a priori to only 1/8 if her PLT is negative. The risk for the mother of heterozygote girl falls from 1/2 a priori to 1/16 if her PLT is negative. PMID- 2903705 TI - Clinical toxicity of cocaine adulterants. AB - Adulterants are found in all street samples of cocaine. They add an unappreciated dimension to the clinical toxicity of cocaine abuse. Identification of these adulterants is necessary to separate their effects from those of cocaine. The comprehensive toxic screen, which provides multiple modalities of drug analysis, will be a key diagnostic tool in the further investigation of these inherently toxic agents and their impact on syndromes of cocaine intoxication. PMID- 2903706 TI - Modulatory effect of neurotransmitters and neurotropic drugs on the release of 3H D-aspartic acid from synaptosomes. PMID- 2903707 TI - Serotonin-glutamate interaction in rat cerebellum: involvement of 5 hydroxytryptamine receptor subtypes. PMID- 2903708 TI - Investigations on dynorphin structurally-related opioid peptides. I. Impact on nociceptive transmission. II. Regulation of pituitary content. PMID- 2903709 TI - Receptor organization of opioid and adrenergic regulation of pain. PMID- 2903710 TI - Ethological pharmacology of anxiogenic and anxiolytic drugs. PMID- 2903711 TI - Analysis of the mechanism of psychotropic action of a 3-hydroxypyridine derivative. PMID- 2903712 TI - Plasma sex steroid transport and histamine H2-receptor antagonists. Clinical implications. PMID- 2903713 TI - Effects of dietary alpha- and gamma-linolenic acid on lipid metabolism in young and adult rats. AB - The effect of age on lipid metabolism was studied in rats fed diets containing safflower oil (SFO, 78% linoleic acid), evening primrose oil (EPO, 9.4% gamma linolenic acid and 70% linoleic acid) or the mixture of safflower and linseed oil (SLO, 10.2% alpha-linolenic acid and 68% linoleic acid). The activity of hepatic HMG-CoA reductase declined with age in all groups. In adult rats, the reductase activity was high in the EPO group and low in the SLO group. The activity of hepatic cholesterol 7 alpha-hydroxylase was independent of the diet or age. Hepatic delta 6-desaturase activity was low in adult rats fed EPO. In liver microsomal phospholipids, the percentage of 22:5 n-6 decreased while that of 22:6 n-3 increased with age. The ratio of linoleate metabolites to linoleate was high in the EPO group and low in the SLO group. Liver and serum cholesterol increased with age only in rats fed the SLO diet. Thus, the results indicated an enhanced susceptibility to dietary fats with age. PMID- 2903714 TI - [13 cases of drug-induced calculi]. AB - All urinary stones should undergo detailed studies to identify those related to drug therapy. Among 520 stones analyzed by infrared spectrophotometry, we found 13 drug-induced stones (13/520: 2.5%). Drug-induced stones were caused by glafenine in 7 cases, piridoxylate in 4 cases, triamterene in one case and an unknown organic compound in one case. Glafenine stones appear to develop more readily in infected urine. Triamterene stones are often associated with uric acid disorders. Piridoxylate induces the formation of glyoxylate which is responsible for hyperoxaluria and formation of oxalocalcium stones. PMID- 2903715 TI - Cloning and expression of methicillin resistance from Staphylococcus epidermidis in Staphylococcus carnosus. AB - A 6.2-kilobase chromosomal DNA fragment from a methicillin-resistant Staphylococcus epidermidis strain was cloned into Staphylococcus carnosus by using staphylococcal plasmid pCA44 as the vector. The recombinant plasmid obtained, pBBB21, conferred methicillin resistance on its host and was responsible for the synthesis of a low-affinity penicillin-binding protein (PBP), PBP 2'. PBP 2' determined by the S. epidermidis DNA and expressed as a membrane bound PBP in S. carnosus reacted with monoclonal antibodies directed against PBP 2' of Staphylococcus aureus origin, and the cloned S. epidermidis DNA hybridized to the methicillin (mec)-specific DNA from S. aureus. These findings point to a common origin of the methicillin resistance determinant in staphylococci. PMID- 2903717 TI - Do carbohydrates affect food intake via neurotransmitter activity? AB - The consumption of a carbohydrate-rich, protein-poor meal or snack can increase the synthesis of the brain neurotransmitter serotonin; proteins block this effect. The mechanism of the rise in brain serotonin involves the secretion of insulin, and the decrease that the hormone produces in plasma levels of certain amino acids that compete with tryptophan, serotonin's precursor, for transport across the blood-brain barrier. The rise in serotonin can thus be produced by any carbohydrate that elicits insulin secretion, independent of its sweetness. Pharmacologic treatments that amplify serotonin-mediated neurotransmission can selectively decrease the consumption of carbohydrate (i.e., in relation to that of protein). A group of diseases seems to exist in which depressive symptoms are associated with "carbohydrate-craving", and the consumption of large quantities of carbohydrate-rich, protein-poor snacks. Patients describe positive subjective responses to the dietary carbohydrates which are unrelated to hunger. These responses may be mediated by the rise in brain serotonin. PMID- 2903716 TI - Influence of berberine sulfate on synthesis and expression of Pap fimbrial adhesin in uropathogenic Escherichia coli. AB - We investigated the influence of berberine sulfate, an ancient Chinese antibiotic, upon the adhesion of uropathogenic Escherichia coli to erythrocytes and epithelial cells. Although berberine sulfate in increasing concentrations had no effect on bacterial growth or on the synthesis of major outer membrane proteins of the E. coli organisms, it increasingly blocked adhesion. The decreased adhesion was accompanied by a reduction in the synthesis of fimbrial subunits and in the expression of assembled fimbriae. These results suggest that the anti-infectious activity of berberine sulfate in E. coli-induced urinary tract infections may be mediated by the selective suppression of the synthesis and assembly of fimbriae by uropathogenic organisms. PMID- 2903719 TI - [Computerized tomography of the petrous bone. With magnetic resonance tomography]. PMID- 2903718 TI - Electroporation-induced transformation of intact cells of Clostridium perfringens. AB - Electroporation-induced transformation of intact cells of Clostridium perfringens 3624A with plasmids pAMB1 and pHR106 resulted in 3.8 X 10(-5) and 4.2 X 10(-4) transformants per viable cell, respectively. With respect to shuttle plasmid pHR106, these values represent a greater than 100-fold increase in transformation frequency when compared with the values reported with polyethylene glycol-induced L-phase variants. PMID- 2903720 TI - Developmental changes of the content of acetyl-CoA carboxylase mRNA in chicken liver. AB - Utilizing RNA blot hybridization and immunoblotting techniques, the changes of the hepatic contents of acetyl-CoA carboxylase mRNA and of the enzyme protein in growing chicks have been investigated. In the post-hatching period, the hepatic mRNA level markedly increased at least 70-fold when compared to that before hatching. This increase was not observed in chicks receiving no diet. These changes were closely paralleled with the rise of the hepatic content of acetyl CoA carboxylase protein in chicks up to 10 days old. Neither the acetyl-CoA carboxylase mRNA level nor the enzyme quantity significantly changed in heart. It is concluded from these results that the developmental regulation of acetyl-CoA carboxylase in the post-hatching period of chicks is tissue specific and occurs primarily at a pretranslational step. The content of acetyl-CoA carboxylase mRNA in adult chicken liver was low, which is comparable to those in embryos at 3 days before hatching and chicks at hatching day. Although acetyl-CoA carboxylase mRNA was detected in adult chicken brain, heart, lung, kidney, uropygial gland, spleen, testis, and chest muscle as well as liver, the mRNA level in these tissues was much lower than that in liver of growing chicks. PMID- 2903721 TI - Multiple mechanisms by which glutamine synthetase levels are controlled in murine tissue culture cells. AB - We report the isolation of a complimentary DNA (cDNA) clone encoding glutamine synthetase, derived from a population of methionine sulfoxime-resistant mouse GF1 fibroblasts. When GF1 cells are incubated for 48 h in the presence of the glucocorticoid hormone dexamethasone, the specific activity of glutamine synthetase (GS), assayed as glutamyltransferase activity, increases by threefold. Based on dot hybridization analysis, hormonal treatment also produces a similar increase in the level of GS mRNA. When GF1 cells or mouse Neuro 2A neuroblastoma cells are transferred from medium containing 4 mM glutamine to glutamine-free medium, glutamyltransferase activity increases by at least fivefold. However, the presence or absence or glutamine in the medium does not affect the relative level of glutamine synthetase mRNA in either cell line. With both GF1 and Neuro 2A cells, the half-time for the decline in glutamine synthetase enzyme activity on addition of glutamine to the medium is approximately 1.5 h. This rapid decline, coupled with the lack of effect of glutamine on the level of GS messenger RNA in Neuro 2A cells, renders it unlikely that neural cells alter glutamine synthetase levels in response to glutamine by a biosynthetic mechanism, as suggested by previous authors [L. Lacoste, K.D. Chaudhary, and J. Lapointe (1982) J. Neurochem. 39, 78-85]. PMID- 2903722 TI - [Autologous peripheral stem cell transplantation]. AB - A number of recent reports have now shown that hematopoietic stem cells are present in the circulation, and these cells have the potential to restore complete hematopoiesis following marrow aplasia. Peripheral stem cells have been collected by continuous flow leukapheresis during periods of hematopoietic regeneration after 2 to 3 weeks of intensive chemotherapy. Following marrow ablative chemotherapy or chemoradiotherapy, the autologous peripheral stem cells are thawed and infused intravenously. When a sufficient stem cell dose was given, rapid neutrophil and platelet recovery has been confirmed, as compared with bone marrow transplantation. Acute leukemia, malignant lymphoma and solid tumors may benefit from this approach, and long-lasting remission or cure may result in a significant number of patients. PMID- 2903723 TI - Epidermal lymphocyte chemotactic factor specifically attracts OKT4-positive lymphocytes. AB - Epidermal lymphocyte chemotactic factor (ELCF) from skin overlying a positive tuberculin reaction was compared with the chemoattractants leukotriene B4 (LTB4), N-formyl-methionyl-leukyl-phenylalanine (FMLP), and complement split product C5a (C5a). The chemotactic assay used is a modified Boyden chamber technique. The lymphocytes were subsets of T lymphocytes from healthy young individuals first separated by flotation of E rosettes on Isopaque Ficoll followed by incubation of T cells with anti-CD4 and anti-CD8 monoclonal antibodies and further separation using fluorescence-activated cell sorting. ELCF specifically attracted OKT4+ lymphocytes, while LTB4, FMLP, and C5a induced significant migration in both OKT4+ and OKT8+ lymphocytes without any clear difference between the various chemoattractants or cell populations. We found no blocking of the chemotactic capacity of ELCF when we added antibodies towards IL-1 alpha and IL-1 beta to the chemotactic assay. Further recombinant IL-1 alpha and Il-1 beta did not induce any chemotactic response. Our observation may be of significance in explaining the predominance of OKT4+ cells in allergic contact dermatitis and certain other skin diseases. PMID- 2903724 TI - Calpain activates two transglutaminases from porcine skin. AB - Two transglutaminases (TGase) with estimated molecular weight of 55,000 (55-K TGase) and 120,000 (120-K TGase) were partially purified from the cytosolic fraction of porcine skin (epidermis-rich preparation) using DEAE-cellulose and gel-filtration chromatographies. The enzyme activities of both transglutaminases were enhanced more than 20-fold by treatment with calpain (Ca2+-dependent cysteine proteinase) in the presence of Ca2+, and this enhancement was inhibited by adding EDTA, leupeptin, or an endogenous calpain-specific inhibitor protein (calpastatin). 55-K TGase was effectively activated by a smaller amount of calpain than was 120-K TGAse, while known activating reagents such as thrombin and dimethyl sulfoxide or heat treatment preferentially activated 120-K TGase. One of the physiological functions of calpain in the epidermis may be the activation of epidermal transglutaminases. PMID- 2903725 TI - Effect of ace-inhibitors, calmodulin antagonists, acetylcholine receptor blocking, and alpha receptor blocking agents on motility of human sperm. AB - The purpose of this study was to investigate the influence of several pharmacological compounds on the motility and velocity of washed human spermatozoa. Results were evaluated by multiple exposure photography and computer aided picture analysis. The motility-inhibiting effect of the antifertility drug gossypol was confirmed. Gossypol proved to be a potent inhibitor of the angiotensin converting enzyme (ACE) detectable in high concentrations in seminal plasma. However, human sperm motility was not inhibited during incubation with two other specific ACE-inhibitors (captopril, enalapril). On the contrary, high concentrations of captopril even showed a slight motility-stimulating effect. These results indicate no direct involvement of ACE in the regulation of sperm motility but suggest a direct interaction of gossypol with the plasma membrane of spermatozoa. To clarify whether or not gossypol blocks membranous ion transport, the effect of well-defined ion transport blocking agents on sperm motility was investigated. It was determined that the acetylcholine receptor blocker alpha bungarotoxin and trifluoperazine, a specific calmodulin antagonist, inhibit sperm motility completely. Since stimulation of sperm motility by captopril may be due to an alpha-mimetic action of this compound, the influence of two alpha receptor blockers (bromocriptine, lisuride) on sperm motility was studied. Although lisuride inhibited sperm motility completely, bromocriptine revealed no influence. A temporary and reversible intervention with membrane transport processes could be a suitable way to regulate human sperm motility and male fertility. PMID- 2903726 TI - Benzodiazepine sedatives and the risk of falling in a community-dwelling elderly cohort. AB - A prospective study of risk factors for falls in the elderly at home was conducted in a cohort of tenants (N = 169) of six senior-citizen buildings in New Jersey. Within this study, we evaluated whether benzodiazepine sedative use was associated with risk of falling. The mean age (+/- SD) of the cohort was 79.8 +/- 7.3 years, and 80% were women. Monthly telephone interviews yielded a total of 77 falls during an average follow-up time of 5.6 months. Benzodiazepine use at baseline was categorized as either none, as needed, or continuous, eg, nightly use. Continuous use appeared to increase the risk of falling in this cohort (unadjusted relative risk [RR] = 1.53, 95% confidence interval = 0.93, 2.52; RR adjusted for age, gender, and follow-up time = 1.82, 95% confidence interval = 0.92, 3.62). Any use of benzodiazepines was related to multiple falls in persons who fell. The risk of falling from continuous benzodiazepine use may be higher in persons with position-sense loss in the toes (RR = 2.00) than in persons without such loss (RR = 1.35). We suggest that periodic review of the need for benzodiazepines in the elderly be made. PMID- 2903728 TI - Pericardial flaps prevent wound complications. PMID- 2903727 TI - [Effects of beta-blockers on hemodynamics of the forearm after tobacco stimulation]. AB - In mild hypertension, a betablocker treatment could reduce cardiovascular events. But in smoking men the benefit disappears and this interaction is unexplained. In 6 healthy non smoking men, we studied the effects of acute oral administration of propranolol (80 mg) pindolol (15 mg) and placebo after cigarette smoking (CS) (two cigarettes within 10 minutes). In a double blind cross over randomized study, arterial pressure and heart rate (HR) were recorded within 20 minutes after CS. Brachial artery diameter (D), Local vascular Resistance (RL), Local arterial Compliance (CL) and pulse wave velocity (VOP) were determined non invasively (using a pulsed doppler system) before and 20 mn after CS. Under placebo, mean arterial pressure (PAM), HR and RL increased significantly after CS (+9.2 +/- 3 mmHg, +4.5 +/- 3 b/mn and +36 +/- 14 per cent, respectively). These modifications were not different after propranolol, pindolol or placebo (ANOVA). Arterial distensibility (CL) was decreased after CS and this alteration was not prevented by beta-blockers. Brachial artery diameter was not modified after CS. Our results demonstrate that acute treatment with non selective beta-blockers with or without sympathomimetic intrinsic activity does not prevent haemodynamic modifications induced by cigarette smoking. PMID- 2903729 TI - Induction of light hydrocarbon nephropathy by p-dichlorobenzene. AB - In order to clarify the etiology of a dose-related increase in the incidence of tubular cell adenocarcinomas of the kidney in male rats, the nephrotoxicity of p dichlorobenzene (p-DCB) was investigated in a subchronic study. Groups of ten male and ten female Fischer 344 rats were dosed by gavage with 0 (controls), 75, 150, 300 or 600 mg p-DCB/kg/day in corn oil. Half of the animals were sacrificed after 4 weeks and the remainder after 13 weeks. Increased urinary LDH and epithelial cell excretion and exacerbation of hyaline droplet accumulation in the cytoplasm of renal cortical cells were observed in male rats over the entire dose range investigated. Tubular single cell necrosis, dilated tubules with granular cast formation in the outer zone of the medulla, were evident in male rats after 4 and 13 weeks of treatment with doses of 150-600 mg/kg/day. In female rats there was no indication of a nephrotoxic action of p-DCB. The effects on the kidney, both in their morphological characteristics and the fact that they occur exclusively in male animals, correspond to the light hydrocarbon nephropathy observed as a result of short-term treatment with a number of aliphatic and cyclic hydrocarbons. The development of cortical renal tumors seems to be associated with this kind of kidney damage which is unique to male rats. The literature on this subject generally regards these renal effects as not predictive for man. PMID- 2903731 TI - [Morphofunctional characteristics of the neuroepithelial bodies in the respiratory organs]. PMID- 2903730 TI - [Endocrine cells in the cardial glands of the esophagus in man]. AB - Distribution of endocrine cells in composition of the secretory epithelium of the cardial glands of the human esophagus in both sex and at various age has been investigated. In spiral paraffin slices the endocrine cells have been revealed by means of different silver impregnation methods (after Grimelius, Masson--Hamperl, Sevier--Munger), Sevke technique, ferry-ferrocyanide method. Some cells have been revealed, which according to the specific signs of their granule staining resemble very much G-, EC-, ECL-cells of the stomach. They can be triangular, flatten or polygonal and are stained in the cardial gland epithelium as single diffuse cells, or as groups of cells. Staining of the slices with aldehyde fuchsin in various modifications reveals dark cells with dark-violet granules and lighter cells with acidophilic granules. Sometimes among these cells certain cells with light-violet cytoplasm are revealed. All these cells can be arranged both in composition of the secretory epithelium of the glands and in conglomerates of cells, resembling pancreatic islands. According to their tinctorial properties they resemble A-, B-, D-cells of these islands. PMID- 2903732 TI - Biochemical screening of airmen. AB - Starting in 1983, biochemical and hematological screening, including hemoglobin, hematocrit, mean cell volume, mean red cell hemoglobin concentration, white blood cell count, ESR, serum creatinine, cholesterol, triglycerides, ASAT (SGOT), ALAT (SGPT), G-GT and blood glucose, was performed in all Icelandic captains, copilots, flight engineers, and air traffic controllers. No hematological abnormalities were observed. One pilot had serum creatinine above 150 mmol.L-1; 48 airmen had serum cholesterol above 8.9 mmol.L-1; 15 had blood glucose above 7.9 mmol.L-1. The pilots had significantly lower serum triglycerides, ALAT, and ASAT than the captains. Fifty airmen had G-GT values above 50 IU.L-1. This group was urged to reconsider their alcohol habits and given medical and psychological advice as indicated. In this group the mean G-GT fell from 89 to 37 IU.L-1 during a period of approximately 2 years. No change in G-GT values was observed in those airmen who had a normal initial value. This study demonstrates the value of routine biochemical testing for airmen, particularly as regards blood glucose, serum cholesterol, and G-GT. PMID- 2903733 TI - Programmed environment management of confined microsocieties. AB - A programmed environment is described that assists the implementation and management of schedules governing access to all resources and information potentially available to members of a confined microsociety. Living and work schedules are presented that were designed to build individual and group performance repertoires in support of study objectives and sustained adaptation by participants. A variety of measurement requirements can be programmed and standardized to assure continuous assessment of the status and health of a confined microsociety. PMID- 2903734 TI - Opioids stimulate sarcolemmal NAD(P)H-vanadate dehydrogenase activity. AB - The present study demonstrates that the bovine cardiac sarcolemma possesses an NAD(P)H dehydrogenase activity which is able to oxidize both NADH and NAD(P)H in the presence of vanadate as an electron acceptor. The NADH dehydrogenase activity was significantly higher than the NAD(P)H dehydrogenase activity and both of them were almost completely inhibited by superoxide dismutase and atebrin and markedly reduced by the addition of the protonophore 2,4-dinitrophenol. The incubation of the sarcolemma in the presence of 10(-10), 10(-9), 10(-8) M methionine enkephalin, a prevalent delta-opioid receptor agonist, or dynorphin A (1-17), a prevalent kappa-receptor agonist, produced a dose-dependent increase in the NAD(P)H dehydrogenase activity, with 10(-10) and 10(-9) M dynorphin A (1-17) more effective than the corresponding doses of methionine-enkephalin. The preincubation of the sarcolemma in the presence of superoxide-dismutase, atebrin or 2,4-dinitrophenol strongly inhibited the opioid-stimulated dehydrogenase activity. The stimulatory action elicited by 10(-8) M methionine-enkephalin or dynorphin A (1-17) was completely antagonized by 10(-8) M naloxone or Mr 1452, respectively, whilst 10(-8) M naloxone exerted only a partially antagonistic action against the effect produced by 10(-8) M dynorphin A (1-17), significantly more accentuated than the action of 10(-8) M Mr 1452 versus the same dose of methionine-enkephalin. PMID- 2903735 TI - Synthetic peptides based on the calmodulin-binding domain of myosin light chain kinase inhibit activation of other calmodulin-dependent enzymes. AB - Nanomolar concentrations of synthetic peptides corresponding to the calmodulin binding domain of skeletal muscle myosin light chain kinase were found to inhibit calmodulin activation of seven well-characterized calmodulin-dependent enzymes: brain 61 kDa cyclic nucleotide phosphodiesterase, brain adenylate cyclase, Bordetella pertussis adenylate cyclase, red blood cell membrane Ca++-pump ATPase, brain calmodulin-dependent protein phosphatase (calcineurin), skeletal muscle phosphorylase b kinase, and brain multifunctional Ca++ (calmodulin)-dependent protein kinase. Inhibition could be entirely overcome by the addition of excess calmodulin. Thus, the myosin light chain kinase peptides used in this study may be useful antagonists for studying calmodulin-dependent enzymes and processes. PMID- 2903736 TI - Inhibition of alpha 2-adrenergic receptor-mediated cyclic GMP formation by a phorbol ester, a protein kinase C activator. AB - alpha 2-adrenergic receptor-mediated signal transduction in rat adrenocortical carcinoma cells occurs through the opposing regulation of two second messengers, cyclic GMP and cyclic AMP, in which guanylate cyclase is coupled positively and adenylate cyclase negatively to the receptor signal. We now show that in these cells phorbol 12-myristate 13-acetate (PMA), a known activator of protein kinase C, inhibits the alpha 2-agonist (p-aminoclodine)-dependent production of cyclic GMP in a dose-dependent and time-dependent fashion. The half-maximal inhibitory concentration of PMA was 10(-10) M. A protein kinase C inhibitor, 1-(5 isoquinolinyl-sulfonyl)-2-methyl piperazine (H-7), caused the release of the PMA dependent attenuation of p-aminoclodine-stimulated cyclic GMP formation. These results suggest that protein kinase C negatively regulates the alpha 2-receptor coupled cyclic GMP system in these cells, a feature apparently shared with the other cyclic GMP-coupled receptors such as those of muscarine, histamine, and atrial natriuretic factor. PMID- 2903738 TI - Deletion of a homeobox gene in myeloid leukemias with a deletion in chromosome 2. AB - Mouse myeloid leukemias are characterized by a frequent deletion in one chromosome number 2. We now show that there is a deletion of one copy of the Hox 4.1 homeobox gene in the myeloid leukemias with this deletion in chromosome 2. It is suggested that deletion of this homeobox gene plays a role in determining the abnormal developmental program in myeloid leukemia. PMID- 2903737 TI - Facile analysis and purification of deblocked N-terminal pyroglutamyl peptides with a strong cation-exchange sulfoethyl aspartamide column. AB - A high-performance strong cation-exchange Sulfoethyl Aspartamide column was used to analyze and purify five N-terminal pyroglutamyl peptides after treatment with Pyroglutamate Aminopeptidase. The resulting deblocked N-1 peptides possess an increased positive charge and are therefore retained to a greater extent by the column. Salt gradient elution in a pH 3 mobile phase was then used to recover the desired peptides and the purified deblocked peptides were directly subjected to N terminal sequence analysis. The same digests were also chromatographed on a C18 reversed-phase column using standard trifluoroacetic acid-acetonitrile gradient elution. The elution order for the parent peptide and the N-1 peptide on the reversed-phase column was reversed from that on the Sulfoethyl Aspartamide column and the resolution of the two peptides obtained on the reversed-phase column was less than that observed on the cation-exchange column. In addition, the Sulfoethyl Aspartamide column was shown to be useful to monitor the extent of N terminal glutamine cyclization formed during peptide purification and storage. PMID- 2903740 TI - Highly variable minisatellites and DNA fingerprints. PMID- 2903739 TI - Activation of guanylate cyclase and the regulatory role of cyclic 3',5'-guanosine monophosphate. AB - The effect of dithiothreitol on the activity of soluble guanylate cyclase and on enzyme activation by sodium nitroprusside and free stable radical was studied. A higher degree of oxidation of guanylate cyclase from rat platelets in comparison with that of the enzyme from human platelets was found, which influences both the value of the enzyme activity and its regulation. It was shown that dithiothreitol enhanced the stimulating effect of nitroprusside but inhibited the activation of guanylate cyclase by free radical, which was suggestive of a difference in the mechanisms of the activating effect of these agents. A scheme of the biological role of cyclic 3',5'-guanosine monophosphate was proposed. On the basis of this scheme, different pathological states caused by disturbances in the functions of guanylate cyclase were identified and investigated. PMID- 2903741 TI - Xenobiotic and endobiotic inhibitors of cytochrome P-450dbl function, the target of the debrisoquine/sparteine type polymorphism. AB - Five to 10% of Caucasians are poor metabolizers (PM) of debrisoquine, sparteine, bufuralol and numerous other drugs. A deficiency in cytochrome P-450dbl (P 450dbl) function is the cause of this polymorphism of drug oxidation with autosomal recessive inheritance. In the present study, inhibition of bufuralol-1' hydroxylase in human liver microsomes by drugs and chemicals was performed in a search for potential new substrates for this polymorphic enzyme. Among the 80 alkaloids and drugs tested, 25 were competitive inhibitors. In vitro competitive inhibition of bufuralol oxidation by a substance indicates that this compound is able to bind to the same enzymatic site as bufuralol. This may mean that the competing drug also is metabolized by P-450dbl and that its metabolism is subject to the same genetic variation as the oxidation of bufuralol. However, some of these competitive inhibitors are not oxidized by P-450dbl. In this case, however, they may interfere with the in vivo phenotyping procedure by inhibiting the formation of metabolites of test drugs such as debrisoquine, sparteine, metoprolol or dextrometorphan. PMID- 2903742 TI - In vivo effect of tunicamycin on the expression of rat small intestinal brush border membrane glycoproteins and glycoenzymes. AB - Tunicamycin, a known inhibitor of the lipid-dependent glycosylation of proteins, was used in vivo to study the biosynthesis of rat intestinal brush border membrane aminopeptidase N and dipeptidyl aminopeptidase IV. The incorporation of [3H]glucosamine into newly synthesized total protein of mucosal cell homogenates was inhibited by 60%, whereas incorporation of [3H]leucine was decreased only 21% by tunicamycin. This effect was much more pronounced in the brush border membrane fraction isolated from intestinal mucosal cells where incorporation of radiolabled leucine and glucosamine was reduced to 50 and 82% of control values respectively. An examination of the brush border membrane protein profile by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that there was a marked selective decrease in the amount of glycoproteins of molecular weights greater than 130 kD. In addition, there were decreased levels of assayable aminopeptidase N, dipeptidyl aminopeptidase IV and disaccharidase activity in intestinal mucosal cell homogenates and brush border membranes of tunicamycin treated rats. Though tunicamycin decreased incorporation of newly synthesized aminopeptidase N and dipeptidyl aminopeptidase IV protein into brush border membranes by 70-75%, the newly synthesized enzyme that was incorporated was indistinguishable from that of controls. Further, non-glycoslyated forms of both enzymes were not detected in any other subcellular fractions. These results show that tunicamycin, an inhibitor of glycosylation, significantly affected the expression of brush border membrane glycoproteins, suggesting that both polypeptide synthesis and degradation of these proteins may be altered in the presence of this drug. PMID- 2903743 TI - Mouse hepatic cytochrome P-450 isozyme induction by 1,4-bis[2-(3,5 dichloropyridyloxy)]benzene, pyrazole, and phenobarbital. AB - The effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) and pyrazole on mouse hepatic cytochrome P-450 isozyme expression were compared to the P-450 induction pattern elicited by phenobarbital. TCPOBOP and PB administration caused a similar induction profile by increasing microsomal protein and cytochrome P-450 content and the catalytic activities of several monooxygenases in DBA/2N and AKR/J mice. There were, however, several quantitative and some qualitative differences in the induction profile caused by phenobarbital and TCPOBOP. A few strain-related differences were also observed. Immunoblot analysis with polyclonal anti-coumarin hydroxylase (P-450Coh) antibody and epitope-specific monoclonal antibodies 1-7-1 and 2-66-3 showed that both phenobarbital and TCPOBOP increase the amount of P450IIB and P-450Coh. TCPOBOP caused a more pronounced increase in the amount of P-450IIB than phenobarbital, and TCPOBOP also caused an increase in the amount of P-450IA2. These data suggest that in the mouse, TCPOBOP increases mainly the expression of P-450 isozymes responsive to phenobarbital. The effects of pyrazole differed greatly from those caused by TCPOBOP and phenobarbital. In the DBA/2N mice, pyrazole increased coumarin 7-hydroxylation 9.4-fold, whereas in the AKR/J mice the activity was induced only to a level equivalent to the DBA/2N basal level. In immunoblot experiments with anti-P 450Coh antibody, the amount of P-450Coh was considerably higher in DBA/2N mice treated with phenobarbital, TCPOBOP, or pyrazole in comparison with the AKR/J mice, indicating a strain specificity in the inducibility of coumarin 7 hydroxylase by pyrazole. PMID- 2903744 TI - Interindividual variation in phase II detoxification enzymes in normal human colon mucosa. PMID- 2903745 TI - [Primary structure of the OSCP-protein, conferring the oligomycin sensitivity to the H+-ATPase complex. II. Hydrolysis of OSCP with proteinase from Staphylococcus aureus and reconstruction of the polypeptide chain]. AB - Hydrolysis of OSCP of bovine heart mitochondria by proteinase from Staphylococcus aureus V8 was followed by isolation of all individual peptides by means of gel filtration and HPLC. Structural analysis of the peptides allowed to arrange BrCN fragments and to reconstruct the complete amino acid sequence of the protein. Comparative structural analysis revealed existence of a certain homology between OSCP and delta- and b-subunits of the E. coli H+-ATPase, which are necessary for interaction of catalytic and proton-conducting parts of the bacterial enzyme. PMID- 2903746 TI - [Amino acid sequence of neurotoxin II from the sea anemone Radianthus macrodactylus]. AB - Amino acid sequence of neurotoxin II isolated from the sea anemone Radianthus macrodactylus was determined by analysis of peptides obtained after its digestion with trypsin and staphylococcal proteinase. It is shown that the polypeptide chain of the toxin consists of 48 amino acid residues, including six cysteines. PMID- 2903747 TI - [Aspartyladenylate analog--effective inhibitor of asparagine synthetase]. AB - A number of earlier unknown phosphonate analogues of aspartyl adenylate with anhydride oxygen substituted by --CH2--, and the carbonyl group substituted by - CH(OH)- or --CH(NH2)-groups were synthesized. These compounds were used to study the reaction mechanism of asparagine synthetases from white lupine and E. coli. The aspartyl adenylate analogues proved to be powerful competitive inhibitors (Ki = 10(-7) M) of the bacterial enzyme. In the case of white lupine enzyme catalyzing the aspartate-independent ATP--[32P]PPi exchange, the above compounds displayed a non-competitive type of inhibition with respect to aspartate and ATP, Ki = 10(-4) M. It is likely that for the latter enzyme the first intermediate is different from an aspartyl adenylate derivative. PMID- 2903748 TI - Nonlinkage of the T cell receptor alpha, beta, and gamma genes to systemic lupus erythematosus in multiplex families. AB - To test the possibility that T cell antigen receptor (TcR) genes are linked to the genes involved in the pathogenesis of systemic lupus erythematosus (SLE), genomic DNA restriction fragment length polymorphisms were studied, using the Southern blot technique, in 5 families with multiple members with SLE, 14 unrelated SLE patients, and 14 normal controls. Polymorphic patterns were detected with probes for all 3 TcR chains, but there was no significant difference in the distribution of the restriction fragment length polymorphism pattern among the patients, the relatives, and the controls. Furthermore, in the families with at least 2 individuals with the disease, each of the 3 TcR chain genes did not cosegregate with the disease. We conclude that TcR alpha, beta, and gamma chain genes are not likely to be linked to genes related to SLE. PMID- 2903749 TI - Genetic variation in the apolipoprotein AI-CIII-AIV gene cluster and coronary heart disease. AB - Six RFLPs in the apolipoprotein (apo) AI-CIII-AIV gene region detected with the restriction enzymes XmnI, MspI, PstI, SstI and PvuII were used to study the role of genetic variation at this locus in the development of coronary heart disease and in the regulation of serum levels of various lipid and lipoprotein parameters in the Austrian population. 106 male patients with coronary heart disease and 118 matched controls were investigated. None of the alleles defined by these RFLPs was associated with increased coronary risk. In the patients, but not in the control group individuals with the genotype P1P2 for the PstI polymorphism in the 3' flanking region of the apo AI gene had significantly lower serum levels of high density lipoprotein (HDL)-cholesterol and apo AI levels than those with the genotype P1P1. The S2 allele of the SstI polymorphism at the 3' end of the apo CIII gene was significantly associated with elevated serum levels of triglycerides in the patient, but not in the control group. Controls with the genotype V2V2 for the PvuII(A) polymorphism at the 5' end of the apo CIII gene had significantly higher serum levels of apo B than those with V1V1 or V1V2. This association did not exist among the patients. These findings suggest that variation associated with some of these RFLPs is contributing to the determination of lipid levels in patients and controls, but that the RFLPs themselves cannot be used as markers for increased coronary risk in the Austrian population. PMID- 2903750 TI - [Long-term therapy with beta-2 mimetics: role of tachyphylaxis]. AB - Long-term treatment with beta-2 agonists are said to induce bronchial adrenergic receptor desensitization. Tachyphylaxis is a pharmacological phenomenon that is usually observed with all the drugs and hormones that stimulate receptors. It plays a regulatory role in coupling-decoupling of hormone and receptor. In asthmatics, loss of bronchial responsiveness to a beta-2 adrenergic stimulation may differ from tachyphylaxis, since many factors contribute to the decrease of the response. Penetration of aerosol depends on bronchial obstruction, hypersecretion and inflammatory processes. Aerosols may induce bronchospasm that is related to propellants, the absorption of oral forms beta-2 agonists may exhibit large variation. Few longitudinal or transversal studies to detect the frequency tachyphylaxis in asthmatics have been done, but it has been shown recently that, in a population of asthmatics who were receiving long-term treatment, loss of bronchial response to beta-2 agonists, possibly related to receptor desensitization, was in a range of 10 to 15%. PMID- 2903751 TI - [Adrenergic therapy and vigilance: beta-2 sympathomimetic aerosols in asthma]. AB - It has been established that the use of beta-2 sympathomimetic aerosols is a safe and efficacious treatment of asthma. Unexpected cases of sudden death amongst insufficiently-treated patients or patients who stopped their treatment are not linked with the use of these drugs. To assess the risk of possible "receptor desensitization" it is necessary to notify these accidents to the Committee on Safety of Drugs and to take into consideration the opposite results of further administration and termination of treatment. PMID- 2903752 TI - [Behavior of circulating somatostatin in cirrhotic subjects: correlation with hepatic function]. PMID- 2903753 TI - New anti-H2 agents assayed at the mouse end-plate: electrophysiological and in vitro studies. PMID- 2903754 TI - [Enzymuria and creatinine clearance in the clinico-laboratory evaluation of kidney damage in urological disease]. PMID- 2903755 TI - [Semen parameters in patients affected with urological diseases (varicocele, cryptorchism, testicular tumors and genital tract infections)]. PMID- 2903756 TI - Effects on urine profiles of diatrizoate in hydrated and dehydrated rats. A double cross-over study. AB - Effects of intravenous diatrizoate on urine profiles in hydrated and dehydrated rats were compared. In 12 normal rats albumin, glucose, sodium, and the enzymes LDH and GGT were followed twice over 3 hours. The 6 rats being dehydrated at the first examination were hydrated 28 days later and vice versa. At both examinations diatrizoate affected all profile components significantly during the first two hours and caused a 3 per cent weight loss in both groups. Only one significant difference between the hydrated and dehydrated rats was found: The excretion of the brush border enzyme GGT was 1.5 times higher in the dehydrated than in the hydrated rats in both series. Thus, the effect of diatrizoate on the tubular brush border seems to depend on the state of hydration in normal rats. PMID- 2903757 TI - Differing interactions between hexamethonium and tubocurarine, pancuronium or alcuronium at the neuromuscular junction. AB - The action of hexamethonium has been investigated in the rat phrenic nerve hemidiaphragm preparation, alone and in combination with the neuromuscular blocking agents tubocurarine, pancuronium and alcuronium. Hexamethonium alone in concentrations between 3.55 x 10(-3) and 7.1 x 10(-3) mol litre-1 produced neuromuscular blockade in a dose-dependent manner. Low concentrations of hexamethonium antagonized the neuromuscular blocking effect of all three neuromuscular blocking drugs, less with tubocurarine than with the other two. Increasing the concentration of hexamethonium produced potentiation of the neuromuscular blocking effect, this being greater with tubocurarine than with either pancuronium or alcuronium. The cholinesterase activity in rat diaphragm homogenates was inhibited by hexamethonium. This inhibition was only significant at concentrations greater than those which resulted in antagonism and cannot, therefore, explain the observed antagonism. The mechanism of these observations is discussed with respect to the known behaviour of a combination of antagonists acting within a receptor system. PMID- 2903759 TI - Comparison of the adductor pollicis and the first dorsal interosseous muscles during atracurium and vecuronium blockade: an electromyographic study. AB - The pattern of neuromuscular blockade in the first dorsal interosseous muscle (1st DI) and the adductor pollicis muscle was compared electromyographically following atracurium or vecuronium. There were no clinically significant differences between the muscles in respect of onset time, maximum blockade, train of-four ratio, or recovery index. There were no problems in recording a consistent electromyogram from the 1st DI, which appears to be well suited to clinical monitoring. PMID- 2903758 TI - Pulmonary kinetics of fentanyl and alfentanil in surgical patients. AB - The pulmonary kinetics of fentanyl and alfentanil were studied quantitatively in two groups of five and six surgical patients, respectively, after the induction of anaesthesia. A mixture of one of the opioids and indocyanine green was administered as a bolus. From measurements of the concentrations of the dye in plasma and the opioids in blood, central blood volume and the amount of drug which passed through the pulmonary circulation were calculated. The pulmonary release of fentanyl and alfentanil was calculated from the arterial-mixed venous blood concentration differences. Fentanyl 43.0-86.9% (median 70.9%) and 35.9 79.8% of alfentanil (median 58.6%) were sequestered by the lung on first passage of the opioid-containing blood through the pulmonary capillaries. During the following 14 min, fentanyl was released, apparently from two binding sites (T1/2fast: 0.22 (0.16-0.27) min; T1/2slow: 5.78 (3.65-13.86) min). Initially, there was a rapid release of alfentanil (T1/2: 0.28 (0.08-0.51) min). However, 1 3 min after injection, the arterial-mixed venous blood concentration differences of alfentanil disappeared, although considerable amounts of drug were still present in the lung of five of the six patients studied. It may be expected that a temporary pulmonary sequestration of fentanyl and alfentanil has considerable impact on the time course of their pharmacological effects, on the time necessary to reach their maximum effect and on the intensity and (in case of fentanyl) the duration of these effects. PMID- 2903760 TI - Infusion of vecuronium assessed by tactile evaluation of evoked thumb twitch. AB - In 15 patients (ASA I-II) undergoing intraabdominal gynaecological surgery, muscle paralysis for tracheal intubation and surgery was achieved by a combined bolus and demand infusion of vecuronium. The initial loading dose of 67 micrograms kg-1 and the rate of subsequent infusion were determined by evaluation of the tactile twitch response to train-of-four (TOF) stimulation of the ulnar nerve while the neuromuscular blockade obtained was recorded blindly for control on the contralateral arm. A maintenance dose of 4.9 mg h-1 (2.0-7.6 mg h-1) produced a smooth course of blockade with minimum and maximum values of twitch height during infusion of 2% and 12%, respectively. A period of 15.9 min elapsed from the end of infusion to a TOF-ratio of 0.7, when neostigmine 2.5 mg was administered at the point of two palpable twitches to TOF-stimulation. Simple tactile evaluation of peripheral nerve stimulation is sufficient to determine the infusion rate of vecuronium required to produce stable and appropriate neuromuscular blockade during intra-abdominal surgery. PMID- 2903761 TI - Atracurium or vecuronium for MHS patients? PMID- 2903762 TI - Pharmacokinetics of mifentidine after single and multiple oral administration to healthy volunteers. AB - 1. The pharmacokinetics of mifentidine, a new long acting histamine H2-receptor antagonist, were studied using two protocols. 2. In one study, on 5 different days six normal male subjects were given 2.5, 5, 10, or 20 mg mifentidine or placebo orally 60 min before starting a 3 h continuous gastric aspiration during which time blood samples were taken for measurement of mifentidine concentration. 3. The area under the curves of mifentidine plasma levels (AUC) vs time for the four doses was linearly related to the dose for each individual subject (r = 0.972, P less than 0.001). After doses of 2.5, 5, 10 and 20 mg, mifentidine reduced hydrogen ion output by respectively 36, 37, 60 and 75% and secretory volume by 1, 17, 40, and 47%. The effects at the two highest doses were statistically significant. AUC was correlated positively with the percentage reduction in hydrogen ion output (r = 0.802, P less than 0.001) and volume (r = 0.834, P less than 0.001) over a 3 h period. 4. In the second study, the pharmacokinetics were evaluated after once-daily treatment for 14 days in seven subjects given 10 mg and in seven others subjects given 20 mg. 5. After multiple dosing, renal clearance was similar for the two doses (11.6 +/- 2.11 l h-1 for the low dose and 17.0 +/- 2.0 l h-1 for the high dose). Plasma half-life (t1/2 lambda 2) was 16.0 +/- 3.0 h after the 10 mg dose and 11.9 +/- 1.2 h after 20 mg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903763 TI - Venous involvement in Takayasu's disease: does it exist? AB - We describe the case of a 46-year-old man with an isolated superior vena cava syndrome, which was relieved by surgery. Pathologic examination revealed segmental involvement of the superior vena cava with dense collagen sclerosis. Histiomonocytic inflammatory transmural infiltration of all layers was histologically compatible with lesions described in Takayasu's disease. Although not previously described, this pathologic aspect suggests the possibility of venous involvement in this disease. PMID- 2903764 TI - Embryonic haemopoietic stem cell grafts in the treatment of murine genetic anaemia. AB - Embryonic haemopoietic stem cells obtained from early post-implantation mouse embryos can be successfully used in the treatment of murine genetic anaemia. Anaemic recipients had either chronic macrocytic anaemia, which was lethal without treatment, or mild anaemia without increased mortality. All successfully grafted recipients developed donor haemoglobin and glucose phosphate isomerase electrophoretic markers, indicating the presence of donor erythrocytes and lymphocytes. The minimum number of embryonic cells resulting in a successful graft in chronic macrocytic anaemia recipients was 0.8 x 10(6) nucleated cells. Athymic (nude) mice were also colonized by embryonic haemopoietic stem cells. Donor electrophoretic markers were seen but all recipients soon died, possibly of pneumonia. Bone marrow grafts into recipients with chronic macrocytic anaemia were not successful. Bone marrow grafts into recipients with mild anaemia resulted in some recipients showing donor markers. These recipients later died, showing symptoms of graft-versus-host disease. PMID- 2903765 TI - The molecular basis of thalassaemia major and thalassaemia intermedia in Asian Indians: application to prenatal diagnosis. AB - A study of the molecular pathology of beta thalassaemia in the Asian Indian immigrant population in the U.K. included 37 patients with thalassaemia major and 14 with thalassaemia intermedia. Using a combination of oligonucleotide probe hybridization and restriction endonuclease analysis the mutations in 100/102 (98%) of the beta thalassaemia genes were characterized. Nine different types were found, of which six are associated with beta zero, one with severe beta+ and two with mild beta+ thalassaemia. Comparison of the beta-globin gene cluster haplotypes, alpha globin genotypes and beta gene mutations of the thalassaemia major group with the thalassaemia intermedia group suggests that the co inheritance of a high Hb F determinant associated with the - + - + + 5' beta haplotype and the inheritance of a mild beta-thalassaemia mutation are the major ameliorating factors of disease severity in Asian Indians. In comparison with other population groups. beta thalassaemia in Asian Indians is not associated with one or two predominant mutations. Despite this, prenatal diagnosis by direct detection is possible in the majority of families by restriction analysis and a limited number of oligonucleotide probes since the majority of severely affected individuals are homozygous for a single mutation. The characterization of these mutations should be useful for the planning of prenatal diagnosis programmes for beta thalassaemia in other Asian Indian communities. PMID- 2903766 TI - Visual recovery in orbital vasculitis. AB - A 46-year-old woman with polyarteritis nodosa and chronic renal failure developed sudden loss of vision which was associated with orbital vasculitis. Treatment with cyclophosphamide produced rapid improvement in vision, which has been preserved with maintenance doses of cyclophosphamide and prednisolone. PMID- 2903767 TI - Multiple species of myeloperoxidase messenger RNAs produced by alternative splicing and differential polyadenylation. AB - Three clones of full-length cDNA encoding human myeloperoxidase were isolated from a human leukemia HL-60 cell cDNA library in lambda gt10 and characterized. Analysis of the nucleotide sequence of one of the cDNA clones, lambda MP-H17, indicated that the cDNA contained 3207 bp with an open reading frame of 2238 bp, a 5' noncoding region of 159 bp, a 3' noncoding region of 800 bp, and a poly(A) tail of 10 bp. cDNA of the two other clones, lambda MP-H7 and lambda MP-H14, each contained insertions with shorter sequences of 96 and 82 bp, respectively, on the open reading frame of lambda MP-H17 cDNA. A myeloperoxidase genomic clone was isolated, and the structure of its 5' region was determined and compared with the structures of these cDNAs. The comparison revealed that the three cDNAs were derived from myeloperoxidase mRNAs produced by alternative splicing from a transcript of the single gene. Nucleotide sequence analysis of the 3' region of the cDNAs of several clones indicated that the mRNAs were polyadenylated at five different sites. Amino acid sequence determination of the amino-terminal and carboxy-terminal portions of the myeloperoxidase light and heavy chains revealed that, during processing of a precursor polypeptide into the mature protein, the amino-terminal polypeptide, the small peptide between the light and heavy chains, and the carboxy-terminal amino acid were excised. PMID- 2903768 TI - Azidobenzamido-008, a new photosensitive substrate for the 'multispecific bile acid transporter' of hepatocytes: evidence for a common transport system for bile acids and cyclosomatostatins in basolateral membranes. AB - Cyclo(-Phe(p-NH[1-14C]Ac)-Thr-Lys-(CO(p-N3)C6H4)-Trp-Phe-DPro++ +), in the following named azidobenzamido-008, was synthesized in order to identify binding sites for c(Phe-Thr-Lys-Trp-Phe-DPro), named 008, (a cyclosomatostatin with retro sequence) in liver cell plasma membranes. In the dark the above photolabel was taken up into isolated hepatocytes, inhibiting the sodium dependent uptake of cholate and taurocholate in a competitive manner (Ki for cholate uptake inhibition = 1 microM; Ki for taurocholate uptake inhibition = 5 microM). When activated by flashed light the inhibition became irreversible (IC50 for cholate uptake inhibition = 2 microM; IC50 for taurocholate uptake inhibition = 9 microM) and the activated cyclopeptide bound chiefly to hepatocellular membrane proteins of 67, 54, 50, 37 kDa. Excess of the initial 008, or of cholate or phalloidin partially protected the above membrane components against labeling with 14C labeled azidobenzamido-008. In contrast AS 30 D ascites hepatoma cells, known to be deficient in bile acid and cyclosomatostatin transport, could not be specifically labeled by azidobenzamido-008. The membrane proteins preferentially labeled in hepatocytes (50 and 54 kDa) are integral glycoproteins. The 67 kDa protein is a hydrophilic nonglycosylated membrane component. Independent of labeling with 14C-labeled azidobenzamido-008 or with 14C-labeled azidobenzamido taurocholate, the main radioactive peaks in the pH region of 7, 5.5, 5.25 were identical after solubilization with Nonidet P-40 and subsequent isoelectric focusing. Proteins of 67, 54, 50 and 37 kDa could be enriched by use of 008 containing gels in affinity electrophoresis. Binding sites for 008 were not destroyed by SDS or Nonidet P-40 treatment of plasma membranes. PMID- 2903769 TI - Interaction of electrically charged drug molecules with phospholipid membranes. AB - Model membranes (egg-yolk PC liposomes) were exposed to the cationic form of amphiphilic drugs. Microelectrophoresis was used to measure the change of the electrokinetic potential as a function of the drug concentration. By use of the Gouy-Chapman theory the surface potential and surface charge density were calculated. A theoretical model postulating a simple partition equilibrium of the charged drug molecules between the membrane and the aqueous phase in the vicinity of the membrane failed to describe the experimental results. Modification of the partition law by introducing a mechanism of saturation at high drug concentrations, however, resulted in concordance of model and experiment. Some parameters of the model can be used as a means of evaluating the efficiency of neuroactive drugs. PMID- 2903770 TI - Differences in the association of ribosomes with heavy rough and light rough endoplasmic reticulum membranes of MPC-11 cells. AB - The treatment of total endoplasmic reticulum membranes of mouse plasmacytoma cells with EDTA resulted in an abolition of the heavy rough (HR) subfraction, while there was a large increase in smooth (S) membranes. When HR and light rough (LR) endoplasmic reticulum membranes were treated individually with EDTA and re centrifuged on discontinuous sucrose gradients it was observed that HR were converted into S membranes, i.e. membranes virtually devoid of ribosomes. LR membranes were not affected to the same extent but there was a shift to a somewhat lower density. A quantitation of ribosomes released by EDTA showed that 95% of 60 S and 72% of 40 S subunits were removed from HR membranes while for LR membranes the corresponding values were 8.5 and 22.6% respectively. Ratios of radioactivity to absorbance at 260 nm calculated for 40 S and 60 S subunits isolated from HR and LR membranes show that 60 S subunits from LR membranes, in contrast to those from HR membranes, equilibrate only slowly with the free pool of ribosomal subunits. The results indicate that the ribosomes associated with HR membranes are 'loosely bound' and those with LR membranes 'tightly bound'. When poly(A)-containing mRNA isolated from HR and LR membranes was translated in vitro and the products analysed for light-chain immunoglobulin content, it was found that the HR fraction was enriched in light-chain mRNA. PMID- 2903771 TI - Increased transglutaminase activity during skin wound healing in rats. AB - Outer, middle and inner layers from wounded or unwounded rat dorsal skin were separated and extracted first with buffer and then with Triton X-100 and dithiothreitol. The extracts and residues were assayed for transglutaminase activity and tissue transglutaminase antigen. Transglutaminase activities in all skin layers are increased in the period 1-5 days after wounding. Most of the increased activity is in the buffer-soluble fraction in the inner skin layer though there is no corresponding increase in antigen in this fraction. This suggests that there is production of activated soluble tissue transglutaminase in the wounded inner layer. In the 3-5 day wounded outer layer the largest fraction of both activity and antigen is associated with the insoluble residue remaining after extraction with Triton X-100. On DEAE-cellulose chromatography Triton X-100 extracts of the inner layer of wounded skin showed a single major peak of activity, corresponding approximately with rabbit liver transglutaminase; the outer layer showed the same peak plus a different one, eluting at lower salt concentration, which is thought to be epidermal transglutaminase. PMID- 2903772 TI - The role of sulfhydryl compounds in mammalian melanogenesis: the effect of cysteine and glutathione upon tyrosinase and the intermediates of the pathway. AB - The effect of cysteine and glutathione on mammalian melanogenesis has been studied. It has been shown that their action is mediated by two different mechanisms. (a) The reaction of the thiol groups with dopaquinone after the tyrosinase-catalyzed oxidation of tyrosine and dopa. This mechanism leads to the formation of sulfhydryl-dopa conjugates and finally sulfur-containing pigments, phaeomelanins instead of eumelanins. This fact might produce an inhibition of melanogenesis due to the slower rate of chemical reactions involved in the polymerization of such thiol-conjugates when compared to that of indoles. (b) The direct interaction between the sulfhydryl compounds and the tyrosinase active site. This interaction may regulate the activity of the enzyme. It is shown that Harding-Passey mouse melanoma tyrosinase is more sensitive to sulfhydryl compounds than mushroom tyrosinase. Cysteine always produces an inhibition of the tyrosinase hydroxylase and dopa oxidase activities of melanoma tyrosinase, this inhibition becoming greater as the cysteine concentration increases. On the other hand, glutathione produces an activation of the tyrosine hydroxylase activity below 3 mM and an inhibition at higher concentrations. The limit between the enzymatic activation and inhibition appears at glutathione concentrations similar to the physiological levels of this compound found in melanocytes. Although the switch from eumelanogenesis to phaeomelanogenesis occurs at much lower concentrations of glutathione, taking into account these data it is discussed that this sulfhydryl compound may regulate not only the type but also the amount of melanin formed inside melanocytes. PMID- 2903773 TI - Factor XIII-induced crosslinking in solutions of fibrinogen and fibronectin. AB - In solutions containing fibrinogen and fibronectin, factor XIIIa catalyzes the formation of two types of crosslinked polymers: hybrid oligomers consisting of equimolar amounts of fibrinogen and fibronectin, and fibrinogen oligomers. The two types of oligomers are produced in amounts proportional to the starting concentration of fibronectin and fibrinogen in the reaction mixture. Increasing the fibronectin concentration relative to the fibrinogen concentration results in the production of more hybrid and less fibrinogen type oligomers. The lowest molecular weight hybrid oligomer, a dimer, is formed by ligation of one molecule of fibrinogen and fibronectin. The A alpha-chain of fibrinogen and one fibronectin subunit participate in the crosslinking. Larger size hybrid oligomers form by the joining of two hybrid dimers to each other via gamma-chain dimerization in the fibronectin moiety of the dimers. In fibrinogen oligomer formation, fibrinogen molecules are ligated by gamma-chain dimerization in a step wise fashion producing fibrinogen dimers, trimers, tetramers, etc. without A alpha-chain crosslinking. The hybrid type and the fibrinogen type of oligomer grow in size and eventually become crosslinked to each other yielding large molecular weight complexes that interact to form a gel network. PMID- 2903774 TI - Evaluation of phenylthiourea derivatives as inhibitors of transglutaminase catalyzed reaction in Chinese hamster ovary cells. AB - 1-(5-Aminopentyl)-3-phenylthiourea (PPTU), a recently developed inhibitor of the transglutaminase-catalyzed reaction (K.N. Lee, L. Fesus, S.T. Yancey, J.E. Girard, and S.I. Chung, (1985) J. Biol. Chem. 260, 14689-14694) was evaluated as a possible probe to examine the physiological role of transglutaminase (EC 2.3.2.13) in Chinese hamster ovary (CHO) cells. The [14C]PPTU in cell culture was readily taken up by CHO cells and was found to be covalently attached to high molecular-weight proteins which are associated with the particulate fractions. Incubating cell homogenates, in the presence of Ca2+, incorporated the labeled PPTU exclusively into high-molecular-weight proteins that were also undergoing polymerization. PPTU at 0.1 mM, a concentration close to the Ki value reported for inhibition of tissue transglutaminase-catalyzed amine incorporation into the B chain of oxidized insulin, decreased high-molecular-weight protein polymerization, whereas PPTU at the same concentrations showed no effect on CHO cell proliferation or on in vitro calmodulin activation of cyclic nucleotide phosphodiesterase. These results suggest that transglutaminase may not be a constitutive enzyme in cell proliferation. PMID- 2903775 TI - Disappearance of CD4 lymphocyte circadian cycles after autologous bone marrow transplantation. AB - Circadian variations are observed in CD4 lymphocyte count in healthy people. Samples taken of the basal value occurring around 08.00 hr and peak value at midnight made it possible to define the range of cyclic variations. Movement of lymphocytes seems important in accounting for the observed circadian variations. CD4 circadian cycle amplitudes were investigated in 12 patients with autologous bone marrow transplantation. Cycle abnormalities were observed in 7 patients. Two of them had a normal CD4 lymphocyte count. It was therefore possible for functional abnormalities in CD4 lymphocytes to be detected in patients with a normal CD4 count. Because of these results, we are of the opinion that the evaluation of CD4 lymphocyte cycle might be a more sensitive test than the absolute CD4 count itself. PMID- 2903776 TI - [Effects of beta-carotene on genotoxic lesions in the liver under formation and action of carcinogenic N-nitrosodimethylamine]. AB - beta-carotene pretreatment of rats decreased the methylation and formation of single-strand breaks in DNA and also decreased activity of alanine aminotransferase, sorbitol dehydrogenase, gamma-glutamyl transpeptidase activities, caused by action of N-nitrosodimethylamine or synthesis of this carcinogen from precursors. PMID- 2903777 TI - A sensitive gas chromatographic mass spectrometric assay for a novel dopamine agonist (+)-trans-3,4,4A,5,6,10B-hexahydro-4-propyl-2H-naphth(1,2-B)(1,4) oxazin 9-ol in human plasma. AB - (+)-trans-3,4,4A,5,6,10B-Hexahydro-4-propyl-2H-naphth(1,2-B)(1,4) oxazine-9-ol is a novel potent dopamine agonist. A sensitive and specific gas chromatographic/mass spectrometric assay procedure has been developed for the determination of the dopamine agonist at low picogram per millilitre levels in human plasma. The method comprises an extraction of the agonist from human plasma and subsequent derivatization of the phenolic functionality with pentafluoropropionic anhydride. The derivative is quantified by gas chromatographic and mass spectrometric detection using selected ion monitoring. The assay is linear over the concentration range 10-1000 pg ml-1. PMID- 2903778 TI - Intravenous beta agonist in severe acute asthma. PMID- 2903779 TI - Junior hospital doctors: tired and tested. PMID- 2903780 TI - Flumazenil: a benzodiazepine antagonist. PMID- 2903781 TI - Spontaneous perirenal haematoma secondary to polyarteritis nodosa. AB - Spontaneous perirenal haematoma (SPH) is an unusual but serious complication of polyarteritis nodosa (PAN). We present 3 patients with PAN-associated SPH. One was diagnosed pre-operatively and underwent emergency nephrectomy in order to stop the persistent bleeding; the second patient had surgical drainage of the haematoma and the third recovered without undergoing surgery. The diagnosis is discussed. PMID- 2903782 TI - Undescended testis: a dual lesson. PMID- 2903783 TI - Polyarteritis nodosa presenting as a ruptured renal mass. PMID- 2903784 TI - Time course of MPTP-induced degeneration of the nigrostriatal dopamine system in C57 BL/6 mice. AB - MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a parkinsonism-inducing dopamine (DA) neurotoxin most effective in primates. MPTP also causes a degeneration of both perikarya and axon terminals of the nigrostriatal DA neurons in C57 BL/6 mice. The time courses of the changes in tyrosine hydroxylase immunoreactive objects, endogenous DA concentrations and specifically bound 3H mazindol as markers of the integrity of DA neurons were studied in substantia nigra and striatum of adult C57 BL/6 mice, after systemic treatment with MPTP or intranigral injections of the catecholamine neurotoxin 6-hydroxydopamine (6 OHDA). A rapid decrease in the three parameters studied was found in the substantia nigra during the first 2 days after MPTP-treatment while the MPTP induced effects in the striatum were more protracted and maximal reduction was observed 7 days after MPTP. A basically similar pattern was found when studying the 6-OHDA-induced anterograde degeneration of the nigrostriatal system. These results indicate that in C57 BL/6 mice, MPTP primarily destroys the DAergic perikarya with a subsequent anterograde degeneration of the striatal axon terminals, although a limited rapid destruction of some striatal terminals cannot be excluded. PMID- 2903785 TI - Dopamine-acetylcholine interaction in the rat striatum: a dual-labeling immunocytochemical study. AB - The relationship between cholinergic neurons and dopaminergic axons in the rat striatum was examined by a dual-labeling immunocytochemical method. Cholinergic neurons were identified by their immunoreactivity for choline acetyltransferase (ChAT), and dopaminergic axon terminals were identified by their positive immunoreactivity for tyrosine hydroxylase (TH). Electron microscopic analysis of dual-labeled sections revealed that while most TH-positive terminals formed synapses with unlabeled striatal neurons and dendrites, a number of TH-positive terminals formed close appositions, highly suggestive of synapses, with both large and small dendrites as well as somata of ChAT-positive neurons. Tight appositions were also found between TH-positive terminals and ChAT-positive terminals. Moreover, TH-positive terminals and ChAT-positive terminals were found to form synapses with common dendrites of unlabeled striatal neurons. These results indicated that 1) dopaminergic axon terminals could interact directly with striatal cholinergic interneurons via tight appositions with distances comparable to conventional synapses; and 2) there is a convergence of dopaminergic and cholinergic axon terminals on noncholinergic striatal neurons. PMID- 2903786 TI - Catecholamine innervation of the rat hypoglossal nucleus. AB - The catecholamine innervation of the hypoglossal nucleus (XII) was investigated immunocytochemically by comparing the distribution patterns of tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine N methyltransferase (PNMT) in the rat. Numerous TH- and DBH-positive profiles were found throughout XII, while only occasional PNMT immunoreactivity was observed. Significantly, the distribution patterns of TH and DBH immunoreactivity were coextensive with the most intense staining found ventromedially along the caudal half of XII. We conclude, therefore, that the catecholamine innervation of XII is largely noradrenergic, and that motoneurons innervating the genioglossi muscles, the principal protrusors of the tongue, are the primary targets of this input. PMID- 2903787 TI - [Antiallergic drugs]. PMID- 2903788 TI - [Stimulation, by acute inflammation, of the proliferation in preneoplastic hepatocyte foci expressing the gamma glutamyl transpeptidase, induced by diethylnitrosamine in adult rats]. AB - Acute inflammation induces 20% of hepatocytes to initiate a mitotic cycle in 10 day-old rats but only 1% in adults. gamma GT-positive cell foci were induced by diethylnitrosamine in the liver of adult rats. Proliferation of gamma GT-positive hepatocytes was increased by the acute inflammation that followed a subcutaneous injection of an irritating substance, but proliferation in the surrounding liver tissue remained at the low control level. This difference of sensitivity to the mitogenic stimulation, which mimics the difference between the sensitivity of hepatocytes in suckling and adult rats, gives gamma GT-positive hepatocytes a proliferative advantage over normal cells. Acute inflammation may thus promote the evolution of preneoplastic foci and hepatoma formation. PMID- 2903789 TI - [Substitution of the dental root by aquatic invertebrate skeletons in animals and man]. AB - The biocompatibility of mammal bone with aragonite and calcite skeletons of aquatic invertebrates (Corals, Molluscs) led us, after animal experimentation, to implant in humans artificial dental roots derived from such invertebrates. These roots, incorporated but not resorbed, serve as supports for a prosthetic crown; they are equipped to isolate the root from the buccal cavity and to ensure shock absorbtion during mastication. The greater ease of implanting artificial teeth and their excellent acceptance will in many cases modify the strategy of current dental treatment. PMID- 2903790 TI - [Effects of isoflurane on the duration of neuromuscular block induced by a single dose of vecuronium bromide]. PMID- 2903791 TI - [Constant-flow drug administration in anesthesia]. AB - The authors describe a technique of constant flow perfusion of several anaesthetic drugs, using a simple formula to adjust the perfusion rate to the weight of the patients. Calculation of dilutions is easy: the drug concentration is equal to ten times the rate, per hour and per kg, in practical cases. The flow rate is then a tenth of the patient's weight. This method is easy to apply to several drugs, of which pharmacokinetic parameters justify this administration mode: alfentanil, etomidate, vecuronium bromide... but clinical and instrumental observations should be taken into account for the adjustment of the flow. PMID- 2903792 TI - Oncological applications of somatostatin analogues. PMID- 2903793 TI - Mr 85,000 membrane protein specifically expressed in adriamycin-resistant human tumor cells. AB - For the characterization of membrane changes related to Adriamycin resistance in tumor cells, we have developed monoclonal antibodies against Adriamycin-resistant human myelogenous leukemia K562 (K562/ADM). In addition to the monoclonal antibodies which recognize P-glycoprotein, we have obtained two monoclonal antibodies (designated MRK4 and MRK20) which recognize an Mr 85,000 membrane protein. Using MRK20 as a probe, we have studied the expression of the Mr 85,000 protein in various human multidrug-resistant and -sensitive cell lines. The Mr 85,000 protein was overexpressed in K562/ADM and in a human ovarian cancer cell line resistant to Adriamycin, 2780AD. The protein, if any, was not detected in other drug-resistant human cell lines such as colchicine-resistant KB cells (KB C4), vinblastine-resistant CEM cells (CEM/VLB100), and vincristine-resistant K562 cells (K562/VCR). We have isolated subclones of K562/ADM cells which express different amounts of the Mr 85,000 protein. The expression of the Mr 85,000 protein diminished when the cells were not kept in Adriamycin, and increased when the clones were kept in the presence of Adriamycin. In contrast, the expression of P-glycoprotein remained constant whether in the presence or absence of Adriamycin during these experiments. These findings suggest that the Mr 85,000 membrane protein is closely related to the resistant mechanism specific to Adriamycin resistance, which is different from that of the pleiotropic drug resistance. PMID- 2903794 TI - Stage-specific expression of SSEA-1-related antigens in the developing lung of human embryos and its relation to the distribution of these antigens in lung cancers. AB - The localization of three carbohydrate antigens, Lex, Ley, and sialylated Lex-i, which are closely related to stage-specific embryonic antigen 1, in the lung of developing human embryos was investigated using specific monoclonal antibodies. In the 38-day-old embryo, when the primitive lung bud has appeared and developed into two lung sacs, only Ley antigen was specifically positive in the proliferating cells in the terminal portion of lung bud. In the 50-53-day-old embryos, the future bronchi were actively developing from the bronchial buds. At this stage, the Ley antigen was maximally expressed and the Lex antigen appeared in the bud cells. In the lung of the 12-week-old embryo, buds for the future bronchioles were lined by simple cuboidal epithelial cells, which were strongly positive for Lex antigen, weakly positive for Ley antigen, and still completely negative for sialylated Lex-i antigen. Sialylated Lex-i antigen finally appeared in 18-week-old embryos, in the cells of the terminal buds for the future alveoli. At this stage, the Lex and Ley antigens were already beginning to disappear and were only weakly positive in cells of terminal buds. At 20 weeks, only sialylated Lex-i antigen was weakly detected in the cells in the terminal buds; after 8 months, all three antigens were essentially not detected in the respiratory cells in most of the embryos examined in this study. Formation of bronchial glands was detected at 18 weeks, where the developing gland cells were specifically positive for sialylated Lex-i antigen. Ciliation of the bronchial epithelial cells started at 12 weeks and propagated thereafter. The ciliation was accompanied by the reappearance of Ley and Lex antigen in the epithelial cells. These findings collectively indicated that the three antigens all have a physiological significance as stage-specific developmental antigens of the human lung; those antigens were specifically present in the bud cells at each important step of the morphogenesis of the human lung, such as cells in the lung buds, bronchial buds, and terminal buds for the formation of the alveolus, and cells differentiating into bronchial gland cells. The three antigens gradually disappear in the later stage of development along with the maturation process of the lung. Stage specific embryonic antigen 1 and related antigens are known to be associated with various human cancers, including lung cancers. We suggest that the expression of these antigens in the lung cancer cells is the result of the retrodifferentiation of the cancer cells to the stages of immature embryonic lung cells. PMID- 2903795 TI - Biosynthesis of cancer-associated sialyl-X antigen by a (1----3)-alpha-L fucosyltransferase of human amniotic fluid. AB - Activity of a hitherto unknown (1----3)-alpha-L-fucosyltransferase that acts on IV3-alpha-NeuAc-nLcOseCer as acceptor substrate was demonstrated in human amniotic fluid. The 14C-labelled product IV3-alpha-NeuAc-III3-alpha-Fuc-nLcOseCer was detected autoradiographically after t.l.c. and identified after desialylation by immunostaining with monoclonal antibody Leu Ml. The enzyme is assumed also to catalyze the last step in the biosynthesis of sialyl-X antigen carried by mucins in human amniotic fluid. PMID- 2903796 TI - Posterior pattern formation in C. elegans involves position-specific expression of a gene containing a homeobox. AB - During postembryonic development in C. elegans, posterior-specific pattern formation requires the gene mab-5. Within the posterior body region, mab-5 activity controls epidermal, neuronal, and mesodermal cell differentiation, and also the direction of cell migration. Here, we show that mab-5 RNA is localized in the posterior body region, indicating that mab-5 activity is targeted to posterior cells, at least in part, by a mechanism that operates at the level of mab-5 RNA synthesis or stabilization. We also show that mab-5 contains a homeobox similar to that of the Drosophila Antennapedia gene. This suggests that mab-5 influences cell differentiation and cell migration by regulating gene expression, and clearly demonstrates that genes containing homeoboxes influence global aspects of pattern formation in organisms other than Drosophila. PMID- 2903797 TI - The C. elegans cell lineage and differentiation gene unc-86 encodes a protein with a homeodomain and extended similarity to transcription factors. AB - Mutations in the gene unc-86 affect development of the nematode C. elegans by altering cell lineages and cell differentiation. We molecularly cloned unc-86 by chromosomal walking from linked polymorphic genetic loci, and identified the gene by locating polymorphisms specific for unc-86 alleles. A transcript containing a 467 amino acid open reading frame was inferred from the DNA sequence of a genomic clone. The unc-86 transcript encodes a protein containing a 158 amino acid sequence, referred to as the pou ("pow") domain, which is strikingly similar to sequences found in three mammalian transcription factors. Within this conserved region, there is a homeodomain related to but distinct from homeodomains previously identified in Drosophila and other organisms. These findings suggest that unc-86 encodes a transcription factor, and that the related mammalian transcription factors may function to control cell fates and cell differentiation. PMID- 2903798 TI - rough, a Drosophila homeobox gene required in photoreceptors R2 and R5 for inductive interactions in the developing eye. AB - The rough mutation in Drosophila disrupts an early stage of ommatidial assembly in the developing eye imaginal disc. Analysis of somatic mosaics suggests that rough gene function is required only in photoreceptors R2 and R5. However, these cells apparently differentiate normally in mutant eye discs and it is the cells that are subsequently added to the ommatidium that behave aberrantly. The rough gene was isolated by P-element transposon tagging, and the mutant can be rescued by transformation with an 8.6 kb genomic fragment. The rough transcription unit is 4.3 kb and consists of three exons that are joined in a 1.3 kb mRNA. The predicted rough protein is 350 amino acids long and contains a homeobox. Taken together, our results suggest that the role of the rough gene product may be to regulate the sending of signals by photoreceptors R2 and R5 to their neighbors in the developing ommatidia. PMID- 2903800 TI - [Cardioprotective and membrane effects of exaprolol]. PMID- 2903799 TI - Iontophoretic localization of Ca-sensitive sites controlling activation of ciliary beating in macrocilia of Beroe: the ciliary rete. AB - Macrocilia are thick compound ciliary organelles found on the lips of the ctenophore Beroe. Each macrocilium contains several hundred axonemes enclosed by a single common membrane around the shaft of the organelle. Macrocilia are activated to beat rapidly and continuously in the normal direction by stimulus triggered Ca influx through voltage-dependent Ca channels (Tamm, 1988). Heat dissociated macrociliary cells are spontaneously active without depolarizing stimuli, providing Ca is present (Tamm, 1988). Here we investigate the spatial distribution of macrociliary Ca channels by iontophoretic application of extracellular Ca to different sites along quiescent, "potentially activated" macrocilia of dissociated cells in Ca-free medium. We find that Ca sensitivity for eliciting motility is highest or resides exclusively on the basal portion of the macrociliary surface. This is the first demonstration of local differences in Ca sensitivity along living cilia or flagella. The Ca-sensitive region coincides morphologically with a reticulum of unfused ciliary membranes at the base of the macrocilium. This ciliary rete is in direct communication with the surrounding sea water. It is likely that the ciliary rete provides the necessary Ca influx to trigger beating by virtue of its greater Ca conductance (i.e., density of Ca channels) and/or greater total membrane area. PMID- 2903801 TI - Effects of palytoxin or ouabain on growth and squamous differentiation of human bronchial epithelial cells in vitro. AB - The effects of the non-12-O-tetradecanoylphorbol-13-acetate type tumor promoter palytoxin on human bronchial epithelial cells was studied in an in vitro serum free culture system. Unlike the results of previous studies with another tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, palytoxin did not induce squamous differentiation of normal bronchial epithelial cells and was equally cytotoxic for normal human bronchial epithelial cells, a human lung tumor cell line, and human bronchial epithelial cells immortalized by infection with adenovirus 12 SV40 hybrid virus (BEAS-2B cells). Palytoxin did not induce a change in free cytosolic Ca2+ concentration of BEAS-2B cells. The effect of palytoxin on the c myc mRNA steady state level in BEAS-2B cells was studied: 1 pM palytoxin increased the steady-state level at 12 and 18 h. Furthermore, the induction was accompanied by an increase in [3H]thymidine uptake. Because palytoxin binds to (Na+ + K+)ATPase, the effects of ouabain were compared to the effects of palytoxin. A ouabain-resistant cell line was as sensitive to the growth inhibitory effect of palytoxin as the parent ouabain-sensitive cell line, suggesting different binding sites to the (Na+ + K+)-ATPase for palytoxin and ouabain. Ouabain also increased the steady-state level of c-myc gene expression, but earlier than palytoxin, and the increase in the level of c-myc mRNA was accompanied by a drop in DNA synthesis. These results suggest that palytoxin does not act by growth stimulation, differential cytotoxicity or terminal differentiation of normal versus neoplastic cells which are proposed mechanisms of tumor promotion. PMID- 2903802 TI - Transformation of rat liver epithelial cells with v-H-ras or v-raf causes expression of MDR-1, glutathione-S-transferase-P and increased resistance to cytotoxic chemicals. AB - We have examined the relationship between transformation and multidrug resistance by employing the v-H-ras or v-raf oncogenes to transform rat liver epithelial (RLE) cells in vitro. The data indicate that transformation of RLE cells with v-H ras or v-raf results in increased resistance to the cytotoxins adriamycin, vinblastine and 2-acetylaminofluorene. This multidrug resistance is accompanied by increasing expression of P-glycoprotein (MDR-1) and glutathione-S-transferase P (GST-P). Thus, neoplastic transformation of RLE cells with v-raf or v-H-ras, independently of chemical exposure, results in multidrug resistance. PMID- 2903803 TI - Significance of gamma-glutamyl transpeptidase and thiols in amino acid uptake by rat pancreatic islets: studies with glutamine and leucine. AB - The importance of gamma-glutamyl transpeptidase, the key enzyme of the gamma glutamyl cycle and of thiols for the uptake of amino acids into rat pancreatic islets was investigated. Both serine-borate, an inhibitor of gamma-glutamy transpeptidase, and serine which does not inhibit this enzyme, but probably is a competitive inhibitor of amino acid uptake, inhibited the uptake of glutamine. The inhibitory effect of serine-borate was not greater than that of serine alone. The uptake of glutamine was not affected by either GSH (reduced glutathione) or diamide (a thiol oxidant). Neither substances affected the uptake of leucine. The results indicate that the uptake of glutamine by rat pancreatic islets is not dependent on the functioning of gamma-glutamyl transpeptidase and that thiols are not important for the uptake of the amino acids glutamine and leucine. PMID- 2903804 TI - Development of hyperthyroidism following primary hypothyroidism: a case report with changes in thyroid-related antibodies. AB - We report a 48-year-old woman who developed hyperthyroidism following primary hypothyroidism. The serum T4 level was initially low and serum TSH level was high with clinical signs of hypothyroidism. The thyroid gland was not enlarged. Therapy with L-T4 was started. Three years later she developed hyperthyroidism; serum free T4 increased to 29.1 pmol/l after cessation of L-T4 therapy. The 123I thyroid uptake was increased with no suppression by exogenous T3. When she was hypothyroid, the activity of thyroid stimulating antibodies (TSAb) in serum measured by cyclic AMP production in cultured porcine thyroid cells were negative at 93.4% (normal less than 140%), while thyroid stimulation-blocking antibodies (TSBAb) determined by inhibition of TSH-induced cyclic AMP increase were positive at 96.1% (normal less than 40%). When hyperthyroidism subsequently occurred, TSBAb became negative (30.9%), while TSBAb became positive (163.3%). The findings indicate that hypothyroidism due to the potent TSBAb activity is not always persistent, but can be changed when various types of thyroid-relating antibodies change in the course of the disease. PMID- 2903805 TI - Neurofibromatosis associated with somatostatinoma: a report of two patients. AB - Two patients with neurofibromatosis and somatostatinoma are described, one patient in addition having a parathyroid adenoma diagnosed post mortem. The other patient had a partial somatostatinoma syndrome with diabetes, abdominal pain and cholelithiasis. The tumour was diagnosed preoperatively and metabolic studies demonstrated mild diabetes mellitus apparently due to suppression of insulin secretion by somatostatin, since oral glucose tolerance returned to normal post operatively despite hemipancreatectomy. The tumour also secreted gastrin. There are now 18 reported cases of neurofibromatosis and duodenal carcinoid tumours which makes a genuine association between these two conditions very likely. With the present two cases, seven of the carcinoid tumours in this group have been positively identified as somatostatinomas. The histological finding of psammoma bodies is important in the diagnosis of duodenal somatostatinomas. PMID- 2903806 TI - First-trimester diagnosis of metachromatic leucodystrophy. AB - Two pregnancies at risk for late infantile metachromatic leucodystrophy were monitored by assaying arylsulphatase A at 0 degrees C in homogenates of chorionic villi. In one, the very low activity recorded indicated the fetus to be affected, and this was confirmed by demonstration of low arylsulphatase A activity in cultured villi and cultured fetal fibroblasts after termination. In the other pregnancy, normal activity was found in the villi and the pregnancy is continuing. This simple chromogenic assay appears to be reliable for first trimester diagnosis of metachromatic leucodystrophy. However, there is a probability of mis-diagnosis if the standard assay at 37 degrees C is used. PMID- 2903807 TI - Newer H2-receptor antagonists. Clinical pharmacokinetics and drug interaction potential. AB - Since H2-receptor antagonists are widely and successfully used in the treatment of peptic ulcer, several alternatives to the standard agents cimetidine and ranitidine have been developed. Promising 'new' candidates might be famotidine and nizatidine. For proper selection of the appropriate drug, its pharmacokinetic properties and interaction potential should be known. All 'old' and 'new' H2 receptor blockers are eliminated relatively rapidly (t 1/2 ranges from 1.5 to 4 hours), mainly by the renal route (glomerular filtration and tubular secretion). They exhibit a linear disposition and their distribution is similar. Absorption is most complete for nizatidine, whereas famotidine demonstrates the lowest effective plasma concentrations. Since etintidine shares the same imidazole ring structure as cimetidine, it can also impair oxidative drug metabolism in the liver. In this respect, the non-interacting famotidine and nizatidine (like ranitidine) offer a definite advantage. Based on their very similar pharmacokinetic and interaction profiles, these 2 H2-receptor antagonists might be regarded as alternatives to the older drugs in this group, and at least some economic benefits might result from the competition they will provide. PMID- 2903808 TI - Effects of L-glutamate infusion on the renal utilization of glutamate and glutamine in the dog kidney in vivo during chronic metabolic acidosis or alkalosis. PMID- 2903809 TI - Interaction of glutathione and glutamine in separated rat renal proximal tubules. PMID- 2903810 TI - Allergies in dermatology. Proceedings of a symposium. February 18, 1988, Kauai, Hawaii. PMID- 2903811 TI - Antihistamines and driving safety. AB - The results of two placebo-controlled driving performance studies confirm laboratory data showing that the nonsedating antihistamine terfenadine does not influence the driving performance of users. The amplitude of vehicle weaving calculated for drivers who received this agent did not differ from control values. Neither terfenadine nor loratadine, another nonsedating antihistamine, potentiated the adverse effects of alcohol on driving performance. PMID- 2903812 TI - Effects of terfenadine, diphenhydramine, and placebo on skills performance. AB - The behavioral effects of the antihistamines terfenadine and diphenhydramine were compared in a placebo-controlled, double-blind crossover study. Performance of skills deemed important in safe man-machine interactions was objectively assessed one, three, and five hours after administration of test substances. The results indicate that diphenhydramine use resulted in various degrees of impairment of the ability to perform a visual-search task, a tracking task, a divided-attention task, and a vigilance task. Terfenadine users performed as well as or better than placebo-treated subjects. No differences between terfenadine and placebo were found on a subjective evaluation scale. Diphenhydramine users consistently reported feelings of impairment. PMID- 2903813 TI - Inhibition of skin reactivity by antihistamines. AB - A number of studies have explored the inhibition of antigen-induced skin hypersensitivity reactions by the newer, nonsedating antihistamines such as terfenadine. The collective results of these studies indicate that this inhibitory effect begins within two hours of the administration of a single dose of terfenadine and within three to four days of a single dose of astemizole. Offset of this effect occurs within forty-eight hours of cessation of terfenadine therapy and four weeks or more after the withdrawal of astemizole. The time of onset and offset of this inhibitory effect is indicative of the period of clinical activity of these drugs and thus may be a relevant consideration in selecting an appropriate therapeutic regimen. PMID- 2903814 TI - The relative safety and effectiveness of antihistamines. AB - More than sixty antihistamines are available for the treatment of dermatologic allergies. An appreciation of important differences between these agents is vital to the selection of a therapeutic regimen tailored to a patient's special needs. Duration of action varies among the agents. Data suggest that less frequent dosing schedules may be equally effective, while reducing adverse effects. The degree of sedation, a commonly-reported side effect, varies widely with different antihistamines. Data indicate that the pharmacokinetics of the available antihistamines differ in Orientals and Caucasians as well as in patients of different ages. Further research into possible genetic factors affecting the metabolism of these drugs is needed. In addition, to ensure the best possible quality of care, physicians should become thoroughly familiar with the biology and chemistry of the many antihistamines. PMID- 2903815 TI - The use of antihistamines for the treatment of airway disease. AB - This report reviews studies of the use of antihistamines for the treatment of allergic respiratory diseases. The cumulative results indicate that the nonsedative antihistamine terfenadine, given orally at a dosage of 60 mg twice daily, is effective in the treatment of seasonal allergic rhinitis in both adults and children. No major side effects have been reported, and sensitivity to this agent is not decreased after eight weeks of treatment. Preliminary data on the use of antihistamines for the treatment of asthma are also reviewed. PMID- 2903816 TI - Antihistamines in the treatment of urticarial disorders. AB - A number of studies of the effects of antihistamines on chronic idiopathic urticaria and itch are reviewed. In chronic idiopathic urticaria, terfenadine has been shown to control the number, size, and duration of skin whealing as well as itch. Likewise, in chronic dermatographic urticaria, the minimal force required to produce whealing is increased, while severity of itch is decreased following treatment with terfenadine. In both conditions, however, wheal formation is not completely inhibited, suggesting the involvement of a mechanism unrelated to histamine. In nonurticarial disease in which histamine is not involved in the pathogenesis, antihistamines appear to work as antipruritics, but by a sedative related property and not by antagonism of H1-receptors. PMID- 2903817 TI - Terfenadine in the treatment of chronic idiopathic urticaria and atopic dermatitis. AB - The use of the nonsedating antihistamine terfenadine (60 mg twice daily) in the treatment of chronic idiopathic urticaria and contact urticaria associated with atopic dermatitis was assessed. In patients with chronic idiopathic urticaria, terfenadine was found to be as effective as the traditional antihistamine clemastine in reducing the number of wheals and the severity of itch, without causing drowsiness. A separate study showed terfenadine to be of value in some patients with atopic dermatitis and a history of contact urticaria. PMID- 2903818 TI - Pharmacology and toxicology of nonclassical antihistamines. AB - Within the past five years the introduction of a new class of antiallergy drug, the nonsedating antihistamine, has changed the way allergy sufferers are treated. The first example of this new therapeutic class, terfenadine, is a highly specific H1-receptor antagonist devoid of central nervous system activity. In clinical trials to date involving more than 7,000 allergy patients, terfenadine (60 mg twice daily) has been shown to be unsurpassed in efficacy, to have a rapid onset of action, and to have an incidence of sedation not different from that of placebo and considerably less than that of conventional antihistamines. In addition, results of task performance studies, including on-the-road driving studies, have demonstrated a lack of performance impairment with terfenadine at single oral doses of 60 to 240 mg, or with multiple oral doses of 60 mg twice daily for one week. Furthermore, no interaction has been observed between terfenadine and alcohol or diazepam. Postmarketing surveillance of more than 1 billion patient days has substantiated this remarkably safe and effective clinical profile. PMID- 2903819 TI - Chemical properties of bronchorrhea sputum in bronchial asthma. AB - Bronchorrhea, defined as watery sputum of 100 ml or more per day, was seen in 18 of 207 patients (8.7 percent) with bronchial asthma during attack. Fifteen bronchorrhea sputum samples were chemically examined using ten parameters: dry weight, albumin, IgA, pH, Na+, Cl-, K+, prostaglandins E and F and histamine, and compared with eight saliva samples and 17 mucoid sputum samples. Bronchorrhea sputum differed from saliva in its chemical parameters. Bronchorrhea sputum exhibited parameter values intermediate between those of saliva and mucoid sputum, except for the two following parameters. The pH of bronchorrhea sputum was significantly lower than that of mucoid sputum and histamine concentration, expressed as weight per dry weight of sample, was significantly higher in bronchorrhea than in mucoid sputum. Administration of corticosteroid or an histamine H1-blocker to five to nine asthmatic patients with associated bronchorrhea sputum during asthmatic attacks, significantly reduced the volume of bronchorrhea sputum, whereas anticholinergics and H2-blocker did not alter the sputum volume. PMID- 2903820 TI - Bisoprolol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in hypertension and angina pectoris. AB - Bisoprolol is a beta 1-adrenoceptor antagonist with no partial agonist (intrinsic sympathomimetic) activity or membrane stabilising (local anaesthetic) activity. The oral bioavailability of bisoprolol is high (90%) and the drug has a long elimination half-life which allows once-daily administration; in addition, it is hepatically and renally cleared in equal proportions. In non-comparative studies, and comparative trials, bisoprolol proved effective, and as efficacious as atenolol, low doses of metoprolol, diuretics and nifedipine SR in hypertension, and atenolol and verapamil in stable angina pectoris. Bisoprolol has been well tolerated in most patients. Thus, bisoprolol is an effective alternative to other beta-adrenoceptor antagonists in patients with mild to moderate essential hypertension or stable angina pectoris. Furthermore, its unique pharmacokinetic properties may offer advantages in selected patients. However, the results of further comparative studies with established agents in the treatment of hypertension and angina pectoris are still awaited so that a final assessment of the relative place in therapy of bisoprolol in these disease states may be made. PMID- 2903822 TI - Developmental expression of glial fibrillary acidic protein and glutamine synthetase in serum-free aggregating cell cultures of fetal rat telencephalon. AB - Serum-free aggregating cell cultures of fetal rat telencephalon were examined by a combined biochemical and double-labeling immunocytochemical study for the developmental expression of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS). It was found that these two astroglial markers are co-expressed at different developmental stages in vitro. During the phase of cellular maturation (i.e. between days 14 and 34), GFAP levels and GS activity increase rapidly and in parallel. At the same time, the number of immunoreactive cells increase while the long and thick processes staining in early cultures gradually disappear. The present results demonstrate that in this particular cell culture system only one type of astrocytes develops which expresses both GFAP and GS and which attains a relatively high degree of maturation. PMID- 2903823 TI - [Leukocyte adhesion molecules and their clinical significance]. PMID- 2903821 TI - Sufentanil. A review of its pharmacological properties and therapeutic use. AB - Sufentanil, an opioid analgesic, is an analogue of fentanyl, and has been used for the induction and maintenance of anaesthesia, and for postsurgical analgesia. It has shorter distribution and elimination half-lives, and is a more potent analgesic than fentanyl. In clinical practice, however, intravenously administered sufentanil produces essentially equivalent anaesthesia to fentanyl and is a better anaesthetic than morphine or pethidine (meperidine) for major surgery. It would appear to maintain haemodynamic stability during surgery better than other opioids or inhalational anaesthetics. Postoperative respiratory depression has been reported in a few patients. For outpatient surgery, intravenous sufentanil produces equivalent anaesthesia to isoflurane or fentanyl. Recovery tends to be more rapid after sufentanil and the requirement for postoperative analgesia is less. Initial clinical trials with sufentanil administered epidurally to relieve pain during labour have produced encouraging results, but further studies are required to establish the drug's role in this indication. Epidural sufentanil produces a more rapid onset and better initial quality of analgesia than morphine, buprenorphine or hydromorphine when administered postoperatively, but the duration of analgesia is shorter. Thus, sufentanil's primary place in therapy at this time would appear to be as high dose anaesthesia for major surgery such as cardiac surgery, and as low dose supplement to balanced anaesthesia in general surgery. In addition, low doses administered epidurally seem to have a potential role for analgesia during labour or after surgery although further studies are required to clarify this situation. PMID- 2903824 TI - Organization and rearrangement of immunoglobulin M genes in the amphibian Xenopus. AB - Sequences of immunoglobulin (Ig) cDNA clones of Xenopus laevis show that at least three different VH families are expressed in association with different JH elements and different isotypes of Ig constant regions. In genomic Southern blot analysis, the VH probes for each family hybridize to a distinct set of multiple DNA fragments. In contrast, the genomic JH elements and the IgM constant region gene are localized in a single DNA fragment of approximately 15 kb. Genomic VH elements contain regulatory sequences similar to those in VH genes of shark, fish and mammals and have a leader peptide sequence that contains an intron; they encode the VH region until residue 95 and have heptamer--23-bp--nonamer motifs similar to the rearrangement signal sequences (RSS) in all other vertebrate VH elements. The six genomic JH elements so far sequenced have a nonamer--23-bp- heptamer motif at their 5' end. These RSS motifs imply the existence of DH elements. The comparison of cDNA clones that contain similar constant regions but different VH regions or JH elements suggest rearrangement events. This is shown by Southern blot analysis of erythrocyte and B cell DNA with a JH probe. Thus, the overall organization of the Xenopus Ig gene locus is similar to that of mammals but strikingly different from shark. PMID- 2903825 TI - Activation of protein kinase C or cAMP-dependent protein kinase increases phosphorylation of the c-erbA-encoded thyroid hormone receptor and of the v-erbA encoded protein. AB - The c-erbA proto-oncogene encodes a nuclear receptor for thyroid hormone (T3), which is believed to stimulate transcription from specific target promoters upon binding to cis-acting DNA sequence elements. The v-erbA oncogene of avian erythroblastosis virus (AEV) encodes a ligand-independent version of this nuclear receptor. The v-erbA product inhibits terminal differentiation of avian erythroblasts, presumably by affecting the transcription of specific genes. We show here that the c-erbA-encoded nuclear receptor (p46c-erbA) is phosphorylated on serine residues on two distinct sites. One of these sites, defined by the limit tryptic phosphopeptide 28SSQCLVK, is retained on the v-erbA-encoded P75gag v-erbA protein. This site is located in the amino-terminal domain of these molecules, 21 amino acids upstream of the DNA-binding region. Phosphorylation of this site in both p46c-erbA and P75gag-v-erbA is enhanced 10-fold following treatment of cells with activators of either protein kinase C or cAMP-dependent protein kinase. Since cAMP-dependent protein kinase phosphorylates both p46c-erbA and P75gag-v-erbA in vitro at the same site as that observed in vivo, at least part of the cAMP-dependent phosphorylation of erbA molecules in cells could result from direct phosphorylation by this enzyme. The possible role phosphorylation may play in the function of the erbA-encoded transcriptional factors is discussed. PMID- 2903826 TI - Use of the inhibition of enzymatic antioxidant systems in order to evaluate their physiological importance. AB - Chemical inhibitors of the different antioxidant enzymes were systematically testet either on purified enzymes of after incubation with human fibroblasts in culture. Inhibition values were obtained for catalase with aminotriazole, for superoxide dismutase with diethyldithiocarbamate, for glutathione peroxidase with mercaptosuccinate, for glutathione reductase with bischloroethylnitrosourea and for glutathione synthesis with buthionine sulfoximine. Viability of cells incubated with these inhibitors was then tested under normal conditions and under high oxygen pressure; the data were correlated with the above-mentioned inhibitory values. Cell viability was particularly affected when the glutathione related enzymes, especially glutathione peroxidase, were inhibited. PMID- 2903827 TI - Pharmacokinetics of xamoterol after intravenous and oral administration to patients with chronic heart failure. AB - The pharmacokinetics of xamoterol, a beta-adrenergic partial agonist under clinical evaluation for the treatment of mild to moderate heart failure, have been studied in 8 cardiac failure patients (NYHA Class II) of mean age 62 years. After i.v. dosing, the elimination half-life was 7.4 +/- 0.4 h, the total body clearance was 228 +/- 30 ml.min-1 and the volume of distribution at steady-state was 56 +/- 9 l. 72.5 +/- 4.3% of the dose was recovered unchanged in urine. After the oral dose, the absolute bioavailability of xamoterol was shown to be 5.9%. Peak plasma concentrations occurred 1 to 2.5 h after the oral dose. The apparent elimination half-life was significantly longer after oral doses (16 +/- 2 h) compared to that observed after an intravenous dose. Renal clearance of xamoterol exceeded glomerular filtration rate as measured by creatinine clearance. The pharmacokinetics of xamoterol in cardiac failure patients with good renal function (creatinine clearance greater than 90 ml.min-1) were similar to published data in young healthy male volunteers. PMID- 2903828 TI - A member of a new VH gene family encodes antibromelinized mouse red blood cell autoantibodies. AB - A cDNA clone encoding the variable region of the heavy chain of a BALB/c antibromelinized mouse red blood cell (BrMRBC) monoclonal antibody has been characterized. The nucleic acid sequence indicates that the variable region of the heavy chain is likely encoded by variable-VCP12, diversity-DSP 2 (5, 7 or 8) and joining-JH1 germ-line genes. An identical combination of V genes was observed for six other CBA/J and NZB anti-BrMRBC hybridomas. The BALB/c VCP12 nucleotide sequence is less than 80% homologous to members of the 10 known VH families. Moreover, the genomic restriction fragments detected under moderate stringency conditions with the radiolabeled cDNA probe did not correspond to those obtained with probes of the most homologous VH families (7183 and X24). The results indicate that the VCP12 gene defines a new VH family which we propose to designate VH11. The observation of 1, 2 or 3 genomic restriction fragments at the most, with mice bearing the Igh-Vd or j, Igh-Va or b or Igh-Vc haplotypes, suggests the existence of a few VCP12-related genes. PMID- 2903829 TI - Acute effect of prostaglandins and somatostatin on thymidine uptake of gastric mucosa cells. AB - This study compares the in vivo effect of exogenous administration of prostaglandin E2 (30 micrograms/kg) and its precursor, arachidonic acid (30 micrograms/kg), with the effect of indomethacin (5 mg/kg) on the 6-[3H]thymidine uptake of antral mucosa of mice by autoradiographical methods. Likewise, the effect of somatostatin (30 micrograms/kg) on 6-[3H]thymidine uptake is studied. Evaluation of the number of labeled cells, in the histological sections of the gastric mucosa, showed that arachidonic acid, prostaglandin E2, and somatostatin induced an increase in the number of labeled cells (107, 44, and 45%, respectively), while indomethacin induced a decrease of 32% compared to the control group. These results suggest that prostaglandins may mediate stimulatory effects on thymidine uptake of gastric mucosa cells in the first step after drug administration. PMID- 2903830 TI - Correlation between transglutaminase activity and polyamine levels in human neuroblastoma cells. Effect of retinoic acid and alpha-difluoromethylornithine. AB - The human neuroblastoma cell line SK-N-BE can be induced to differentiate by retinoic acid (RA) or by alpha-difluoromethylornithine (DFMO). The former inducer produces neurite outgrowth, 60% reduction of growth rate, overexpression of neural antigens, and enhanced gamma-aminobutyric acid (GABA) and acetylcholinesterase levels. In contrast, DFMO causes cell body elongation, complete growth inhibition, and higher binding of antibodies directed against neuroectodermal antigens. Polyamine metabolism is also differently affected by the two agents. In particular a large spermine catabolism is induced by RA, while DFMO treatment leads to a small increase in the level of this compound. The neural differentiation induced by RA is accompanied by a marked increase in transglutaminase activity and its induction is paralleled by a transient increase of putrescine and spermidine. The putrescine and spermidine depletion determined by DFMO is accompanied instead by a large inhibition of transglutaminase activity. The inhibiting effect of DFMO treatment on transglutaminase is reversed by the addition of 1 mM putrescine to the culture medium. In the presence of both RA and DFMO a mixed morphological and biochemical pattern is observed. The possibility that the expression of transglutaminase associated to cellular differentiation may be modulated by the level of its substrates is also discussed. PMID- 2903831 TI - Entamoeba histolytica: role of amebic proteinases and polymorphonuclear leukocytes in acute experimental amebiasis in the rat. AB - The injection of 1 x 10(6) trophozoites of axenically grown Entamoeba histolytica strain HM-1 in the subcutaneous tissue of the rat results in an acute and self limited inflammatory process, characterized by the early onset of conspicuous tissue necrosis and focal hemorrhage in the vicinity of the parasites, followed by infiltration with polymorphonuclear leukocytes. The process develops for 5-10 hr but during that period amebic trophozoites progressively disappear, leukocytes undergo degenerative changes, and the lesion tends to heal in 72-96 hr. In leukopenic animals (less than 1000 white blood cells/ml) tissue necrosis and hemorrhage are equally conspicuous in the neighborhood of amebas. Inhibition of amebic proteinase activity prior to injection by heat denaturation, p-hydroxy mercuri-benzoate (PHMB), soybean trypsin inhibitor (STI), and human alpha-2 macroglobulin (alpha 2M), alone or in various combinations, results in absence or notorious decrease in tissue necrosis as well as in clearly diminished inflammatory reaction. This effect is particularly evident when cysteine proteinases are either specifically or generally inhibited. On the other hand, amebic proteinase inhibition with alpha 2M and STI does not interfere with the cell-killing capacity of trophozoites co-incubated in vitro for 2 hr with rat peritoneal cells enriched for macrophages. We conclude that in acute experimental amebiasis produced in the subcutaneous tissue of the rat, amebic cysteine (and perhaps other) proteinases are primarily responsible for necrosis and are also important, but not essential, for inflammation. We also suggest that in this model polymorphonuclear leukocytes are not required for tissue necrosis. Finally, in an in vitro model, the cell-killing capacity of amebas is not influenced by the proteinase activity of the parasite. PMID- 2903833 TI - [Characteristics of the anxiolytic action of benzodiazepine and GABA derivatives on experimentally modelled anxiety states]. AB - The anxiolytic effect of seduxen was revealed in rats in experimentally modelled anxiety states formed by aversive actions of various biological importance. Phenibut and baclofen were found to display no anxiolytic properties on the anxiety model during a conflict situation. The revealed differences of the anxiolytic effect of derivatives of benzodiazepine and GABA indicate diverse spectra of their psychotropic activity. PMID- 2903832 TI - [Influence of antidepressants on benzodiazepine (diazepam and nitrazepam) effects]. AB - Inkazan and pyrazidol given to mice in certain doses were found to reduce the sedative action of diazepam without decreasing its anxiolytic effect but at the same time enhancing the anticonvulsive one. Imipramine diminishes the hypolocomotor action of diazepam and also its anxiolytic effect and exerts no influence on the anticonvulsive effect. All studied antidepressants diminish the hypnotic action on nitrazepam in mice but only inkazan and pyrazidol decrease the sedative-hypnotic effect of nitrazepam in rats. In connection with the lack of the influence on the anxiolytic effect, inkazan and pyrazidol may be used to decrease the sedative side effects of benzodiazepines. PMID- 2903834 TI - [Search for new beta-adrenoblockaders among derivatives of (3-amino-2 hydroxypropoxy) phenoxymethyl isoxazole]. AB - In experiments on anesthetized rats it was found that some derivatives of 2-(3 isopropylamino-2-hydroxypropoxy) phenoxymethyl isoxazole possess marked beta adrenoblocking activity associated with alpha-adrenoblocking properties. The most active compound is 3-methyl-4-chloro-5-(3-isopropylamino-2-hydroxypropoxy) phenoxymethyl isoxazole hydrochloride (compound II) which by its beta adrenoblocking activity is superior to propranolol, oxprenolol and especially labetalol. By its alpha-adrenoblocking activity the compound does not differ significantly from labetalol but it is inferior to phentolamine. Compound II has partial agonistic activity, exerts nonspecific membrane-stabilizing action and exhibits antifibrillatory and antiarrhythmic activity. PMID- 2903835 TI - Association of HLA-DR phenotypes and T-lymphocyte-receptor beta-chain-region RFLP with IDDM in Japanese. AB - Fifty Japanese patients with insulin-dependent diabetes mellitus (IDDM) and 94 normal subjects were genotyped for BglII restriction-fragment-length polymorphism (RFLP) of the T-lymphocyte-receptor beta-chain (TLR beta)-region gene and analyzed in relation to HLA-DR phenotypes. The antigen frequencies of DR4 and DR9 in the IDDM population were significantly higher than those in the normal population, with relative risks of 1.87 (P less than .02) and 2.42 (P less than .01), respectively. Hybridization of digested DNA with the TLR beta probe revealed two alleles of 9.3 and 8.6 kilobases (kb). The allele frequency of 8.6 kb in patients with IDDM (79%) was significantly (P less than .05) higher than that in normal subjects (64%). When TLR beta-region RFLP in IDDM was further analyzed with respect to the HLA-DR phenotypes, the frequency of 8.6 kb was significantly increased in patients with DR4 but not DR9 (DR4/X) and those with DR9 but not DR4 (DR9/X) compared with the frequency found in normal subjects (P less than .05); the relative risks of 8.6 kb in DR4/X and DR9/X were 2.77 and 4.98, respectively. Although the frequencies of HLA-DR phenotypes and of TLR beta region RFLP in IDDM and normal subjects were apparently different from those reported for Caucasians, this population-association study indicates that in the Japanese, genes conferring susceptibility to IDDM exist near or at the HLA-DR and the TLR beta loci, as has been demonstrated in Caucasians. PMID- 2903836 TI - Expression of peptide hormone genes in human islet cell tumors. AB - The embryogenesis of the pancreas suggests the existence of a common stem cell progenitor of the four islet cell types (insulin, glucagon, somatostatin, and pancreatic polypeptide). We investigated whether neoplastic islet tumors express multiple hormone-specific cellular phenotypes of the islets. By analyses of RNA transcripts and immunoreactive peptides in four human insulinomas and one glucagonoma, we found that the insulin, somatostatin, and glucagon genes were coexpressed in all tumors. The expression of the three hormone genes in a lymph node metastasis of a glucagonoma reduced the possibility that contamination of tumor tissue by normal islets occurred. These observations lend further support to the hypothesis of the multipotentiality of neoplastic islet cells for the expression of genes encoding several different islet hormones. PMID- 2903837 TI - beta----alpha----delta pancreatic islet cellular perfusion in dogs. AB - Intraislet communication between alpha-, beta-, and delta-cells and their secretory products may theoretically occur via the paracrine (interstitial) and/or vascular routes. Recently, we have shown that there is a directed microvascular circulation in the rat islet with a cellular order of perfusion of beta----alpha----delta. The direction of microvascular perfusion of cells within the dog islet has been controversial. Anterograde (arterial) perfusion and retrograde (reversed or venous) perfusion of a segment of isolated dog pancreas with potent insulin antibodies yielded results similar to those found in the rat pancreas (anterograde, 158 +/- 44% increase in glucagon and 65 +/- 20% increase in somatostatin; retrograde, no change in glucagon or somatostatin). Anterograde infusion of glucagon antibody (no change in insulin, -33.5 +/- 3% decrease in somatostatin) or somatostatin antibody (no change in insulin or glucagon) also yielded the same results as in the rat pancreas. Anterograde infusion of 500 pg/ml glucagon caused a larger increase in insulin secretion (245 +/- 10%) than retrograde infusion (45 +/- 4%), whereas somatostatin was stimulated more retrogradely (339 +/- 17%) than anterogradely (121 +/- 9%). Anterograde infusion of somatostatin produced a larger decrease in insulin and glucagon than did retrograde perfusion (P less than .0001 for both comparisons). The retrograde infusion of 0.3 mU/ml insulin caused a decrease in glucagon but was without effect anterogradely. The results from the infusion of exogenous hormones suggest that the sensitivity of the alpha-, beta-, and delta-cells to insulin, glucagon, and somatostatin is determined by the beta----alpha----delta order of perfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903838 TI - Skeletal tissue and transforming growth factor beta. AB - Normal skeletal growth results from a balance between the processes of bone matrix synthesis and resorption. These activities are regulated by both systemic and local factors. Bone turnover is dynamic, and skeletal growth must be maintained throughout life. Although many growth promoters are associated with bone matrix, it is enriched particularly with transforming growth factor beta (TGF-beta) activity. Experimental evidence indicates that TGF-beta regulates replication and differentiation of mesenchymal precursor cells, chondrocytes, osteoblasts, and osteoclasts. Recent studies further suggest that TGF-beta activity in skeletal tissue may be controlled at multiple levels by other local and systemic agents. Consequently, the intricate mechanisms by which TGF-beta regulates bone formation are likely to be fundamental to understanding the processes of skeletal growth during development, maintenance of bone mass in adult life, and healing subsequent to bone fracture. PMID- 2903840 TI - Common gastrointestinal diseases in the elderly. AB - Gastrointestinal diseases, such as gastroesophageal reflux (GER) and peptic ulcers, are prevalent in the elderly. These disorders have been found to develop because of an imbalance between aggressive and defensive physiologic factors, but specific causes remain unknown. If neglected or improperly treated, gastrointestinal disease can cause serious complications, particularly in the elderly. Pharmacologic therapy has proven effective for treating both GER and peptic ulcers. PMID- 2903839 TI - Lipogenic potential in liver of the preweanling rat: influence of dietary cholesterol. AB - We examined the effect of a lower dietary cholesterol load on hepatic lipogenic capacity and plasma cholesterol concentrations during the normal suckling period in artificially reared preweanling rats. The artificially reared rats were fed a milk formula that contained low or normal concentrations of cholesterol during the period from the 5th to 17th day after birth. The activities of HMG-CoA synthase and HMG-CoA reductase in livers of 17-day-old rat pups reared on the low cholesterol diet were enhanced three- to five-fold over those observed in the age matched rats in the normal cholesterol and mother-reared control groups. The concentration of cholesterol in plasma of rats reared on the low-cholesterol milk was about 20% lower than that for mother-reared controls. In contrast, rats reared on milk with normal cholesterol content exhibited plasma cholesterol levels about 25 and 50% higher than the mother-reared and low cholesterol groups, respectively. The long-term metabolic consequences of rearing rats on milk formulations without adequate cholesterol remains to be determined. PMID- 2903841 TI - [Suspected airport malaria in Israel]. PMID- 2903842 TI - A specific HPLC method for determination of beta-blockers topically used in ophthalmological diseases. AB - A HPLC method is presented for the identification and quantification in plasma and urine of beta-adrenergic receptor antagonists (betaxolol, carteolol, metipranolol, and timolol) commonly prescribed in ophthalmology. An extraction method is described using pindolol as an internal standard. An RSIL 10 micron column was used. The lower detection limits of the beta-blockers were found to be 4-27 ng/ml. This method is simple, rapid and sensitive; moreover, it allows the determination of 8 other beta-blockers. PMID- 2903843 TI - Activity of DNA modification and restriction enzymes in KGB, a potassium glutamate buffer. AB - A single buffer consisting primarily of potassium and glutamate is shown to be suitable for activity of almost all restriction endonucleases, DNA methylases, and many other DNA-modifying enzymes. The composition of this buffer differs substantially from buffers currently in use for these enzymes. PMID- 2903844 TI - Genetic analyses of restriction fragment length polymorphisms using high molecular weight DNA from sperm or lymphocytes embedded in agarose. AB - A simple and efficient method for determining restriction fragment length polymorphism types on large numbers of individuals using small samples of peripheral blood or sperm cells is described. Whole cells embedded in low gelling/melting temperature agarose were treated with a series of enzyme, detergent, and washing steps to release high molecular weight DNA that was then digested with standard restriction enzymes such as EcoRI and PstI, electrophoresed, blotted, and probed as in normal Southern analyses. The technique should be readily adaptable to any application requiring DNA from small numbers of cells for Southern analyses or pulsed field gel electrophoresis. PMID- 2903845 TI - Rapid DNA purification for restriction fragment length polymorphism analysis. AB - This paper describes a method for isolation of DNA from blood samples involving a rapid chemical disintegration of proteins with 8 M urea and with a minimum of exposure to phenol. The DNA is further desalted and purified on Sephadex G-25 prepacked disposable columns. DNA isolated in this way was pure enough to be immediately cleaved by restriction enzymes. PMID- 2903846 TI - Identification of factor XIIIa in cutaneous tissue. PMID- 2903848 TI - NsiI and ScaI restriction fragment length polymorphisms at the atrial natriuretic peptides (ANP) gene locus. AB - The authors report on two new restriction fragment length polymorphisms at the human atrial natriuretic peptide gene locus, detected in three families with restriction endonucleases ScaI and NsiI. PMID- 2903847 TI - DNA polymorphism haplotypes of the human apolipoprotein APOA1-APOC3-APOA4 gene cluster. AB - The genes coding for apolipoproteins A1, C3, and A4 (APOA1, APOC3, APOA4) are closely linked and tandemly organized within a 15-kilobase (kb) DNA segment on the long arm of human chromosome 11. The nucleotide variability of a 61-kb DNA segment containing these genes and their flanking sequences was studied by restriction analysis of a sample of 18 unrelated Northern Europeans using seven different genomic DNA probes. Eleven restriction site polymorphisms located within this DNA segment were used for haplotype analysis of 129 Mediterranean and 67 American black chromosomes. Estimation of the extent of nonrandom association between these polymorphisms indicated considerable linkage disequilibrium within the APOA1-APOC3-APOA4 gene cluster. Several haplotypes arose by recombination, and the rate of recombination within this gene cluster was estimated to be at least 4 times greater than that expected based on uniform recombination. The polymorphism information content of each of these polymorphisms, taken individually, ranges between 0.053 and 0.375, while that of their haplotypes ranges between 0.858 and 0.862. Therefore, DNA polymorphism haplotypes in the APOA1-APOC3-APOA4 gene cluster constitute a highly informative genetic marker on the long arm of human chromosome 11. PMID- 2903849 TI - The classical and alternate pathways of T cell activation are impaired in leprosy. AB - The proliferative response of circulating T lymphocytes from bacterial index positive lepromatous patients to mitogenic anti-CD3 and pairs of anti-CD2 monoclonal antibodies was significantly reduced. In these patients, the CD2 but not CD3 receptor expression was down-regulated. Further, the CD2 modulation and the associated suppression of proliferative response to monoclonals was brought about in T cells of healthy subjects by prior incubation of mononuclear cells in vitro with Mycobacterium leprae. Thus, the T cell activation pathways through the CD3 and CD2 receptors are impaired in lepromatous leprosy patients and the impairment appears to be due to the modulation of the CD2 receptor specifically by M. leprae. PMID- 2903850 TI - Aortoarteritis, a common cause of renovascular hypertension in Asia. PMID- 2903851 TI - Immunohistochemical distribution of c-erbB-2 in infiltrating and in situ breast cancer. AB - An immunohistochemical study of c-erbB-2 expression was performed on invasive and in situ breast cancer. Strong membrane staining was seen in 16% of the infiltrating ductal carcinomas and 44% of the in situ lesions. c-erbB-2 was overexpressed in ductal rather than lobular tumours. Our results indicate that a small sub-group of breast carcinomas are associated with over-expression of this oncogene which may define an important subgroup of in situ and infiltrating ductal carcinomas. PMID- 2903852 TI - SV40 transfection of human kidney epithelial cells and stability of chromosome 11. AB - Simian virus 40 (SV40) transformation has been used in a variety of mammalian cells and has been shown to extend their life span. We therefore decided to apply these results to normal kidney and tumoral cells derived from Wilms' patients. Wilms' tumour, a nephroblastoma which presents in early childhood, has been linked to deletions and rearrangements in chromosome 11. Analysis of gene structure in the 11p13 locus involved in the development of the tumour has been restricted by the very short life-span of the tumoral cells in vitro. We transfected normal kidney WT/NK, tumoral WT/T cells and human foetal kidney HFK cells with 2 SV40-derived plasmids SV3neo (pBR322-SV40-containing neomycin bacterial gene) and SVori- (pMK-origin mutated SV40). We isolated a high number of SV40-transfected cell lines. The efficiency of transfection appeared to be extremely low in WT/T cells compared with HFK and even WT/NK. The life span of the cell lines was increased in relation to their untransfected homologues. However, in all of the cell lines except 3, senescence occurred, after crisis step or not. We looked at different markers associated with SV40 transformation of mammalian cells and specifically with the presence of SV40 T antigen in the cells and its consequences: AIG, tumorigenicity, expression and insertion in genomic DNA of SV40 T antigen. Genetic studies involving karyotypic and restriction fragment length polymorphism (RFLP) analysis demonstrated that, despite a frequent pseudo-diploidy, the cell lines derived have conserved the 11p13 locus. PMID- 2903853 TI - An investigation of physician assistant and medical student empathic skills. AB - Empathic skill levels in allied health professionals are associated with both patient satisfaction and compliance. These skills have been related to clinicians' educational backgrounds. The primary purpose of this study was to compare the empathic skill levels of health care students having different educational preparation but a similar practice orientation. The secondary purpose was to examine these students' self-perceptions of their own empathic skill levels. The subjects were physician assistant and medical students. Reliability was increased by using four different published instruments to obtain multiple measures on both subject self-ratings and an observer ratings of the subjects. Medical students rated themselves significantly lower (p less than 0.001) than the observers on one instrument, and physician assistant students rated themselves the same as the observers. The scores on observer-rated instruments were consistently higher for physician assistant students than for medical students, but these differences were not statistically significant. PMID- 2903854 TI - Chicken embryo cell line exhibits Japanese quail markers. PMID- 2903855 TI - Gene probes to detect cross-culture contamination in hormone producing cell lines. AB - Cross-culture contamination of cell lines propagated in continuous culture is a frequent event and particularly difficult to resolve in cells expressing similar phenotypes. We demonstrate that DNA-DNA hybridization to blotted endonuclease digested cell DNA effectively detects cross-culture contamination to monitor inter-species as well as intra-species cross contamination. An insulin-producing cell-line, Clone-16, originally cloned from a human fetal endocrine pancreatic cell line did not produce human c-peptide as anticipated. DNA from these cells showed no hybridization to the human ALU sequence probe, BLUR, and lacked restriction fragment length polymorphism typical for the human HLA-DQ beta-chain gene. Although a human insulin gene probe showed a weak, nonhuman hybridization pattern, a cDNA probe for the Syrian hamster insulin gene hybridized strongly consistent with a single copy hamster insulin gene. Karyotyping confirmed the absence of human chromosomes in the Clone-16 cells while sizes, centromere indices, and banding patterns were identical to Syrian hamster fibroblasts. We conclude that the insulin-producing Clone-16 cells are of Syrian hamster origin and demonstrate the effective use of gene probes to control the origin of cell cultures. PMID- 2903857 TI - Mutational analysis of the catalytic and feedback sites of the tryptophan sensitive 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase of Escherichia coli. AB - The nucleotide sequence of aroH, the structural gene for the tryptophan-sensitive 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase [DAHPS(Trp)], is presented, and the deduced amino acid sequence of AroH is compared with that of the tyrosine sensitive (AroF) and phenylalanine-sensitive (AroG) DAHPS isoenzymes. The high degree of sequence similarity among the three isoenzymes strongly indicates that they have a common evolutionary origin. In vitro chemical mutagenesis of the cloned aroH gene was used to identify residues and regions of the polypeptide essential for catalytic activity and for tryptophan feedback regulation. Missense mutations leading either to loss of catalytic activity or to feedback resistance were found interspersed throughout the polypeptide, suggesting overlapping catalytic and regulatory sites in DAHPS(Trp). We conclude that the specificity of feedback regulation of the isoenzymes was probably acquired by the duplication and divergent evolution of an ancestral gene, rather than by domain recruitment. PMID- 2903856 TI - Role of the Bradyrhizobium japonicum ntrC gene product in differential regulation of the glutamine synthetase II gene (glnII). AB - We isolated the ntrC gene from Bradyrhizobium japonicum, the endosymbiont of soybean (Glycine max), and examined its role in regulating nitrogen assimilation. Two independent ntrC mutants were constructed by gene replacement techniques. One mutant was unable to produce NtrC protein, while the other constitutively produced a stable, truncated NtrC protein. Both ntrC mutants were unable to utilize potassium nitrate as a sole nitrogen source. In contrast to wild-type B. japonicum, the NtrC null mutant lacked glnII transcripts in aerobic, nitrogen starved cultures. However, the truncated-NtrC mutant expressed glnII in both nitrogen-starved and nitrogen-excess cultures. Both mutants expressed glnII under oxygen-limited culture conditions and in symbiotic cells. These results suggest that nitrogen assimilation in B. japonicum is regulated in response to both nitrogen limitation and oxygen limitation and that separate regulatory networks exist in free-living and symbiotic cells. PMID- 2903858 TI - Genetic manipulation of major P-fimbrial subunits and consequences for formation of fimbriae. AB - The influence of genetic manipulation of the structural genes coding for major P fimbrial subunits on the formation of fimbriae in Escherichia coli was studied. Deletion of two regions that code for hypervariable parts of the P fimbrillin resulted in strong reduction or total absence of fimbria production. Replacement of deleted amino acids by other amino acid residues restored the formation of fimbriae. The hypervariable regions may be important for biogenesis of fimbriae by imposing correct spacing between conserved regions of the protein. The potential for substituting amino acids in the P-fimbrial subunit opens interesting possibilities for use of fimbriae as carriers of foreign antigenic determinants. An antigenic determinant of foot-and-mouth disease virus (FMDV) was incorporated in the F11 fimbrial subunit. Hybrid fimbriae, recognized by an FMDV specific neutralizing monoclonal antibody directed against FMDV, were formed. PMID- 2903860 TI - cDNA sequence and homologies of the "57-kDa" nucleotide-binding subunit of the vacuolar ATPase from Arabidopsis. AB - Functional and structural similarities among a wide variety of endomembrane H+ ATPases suggest that they form a distinct class with a common origin. Immunological studies (Manolson, M. F., Percy, J. M., Apps, D. K., Xie, X. S., Stone, D. K., and Poole, R. J. (1987) in Proceedings of the Membrane Protein Symposium (Goheen, S. C., ed) pp. 427-434, Bio-Rad, Richmond, CA, and M. F. Manolson, J. M. Percy, D. K. Apps, X. S. Xie, D. K. Stone, M. Harrison, D. J. Clarke, R. J. Poole, unpublished data) support this idea and suggest an evolutionary relationship between the endomembrane and F0F1 ATPases. Further examination of relationships necessitates comparison of protein/nucleic acid sequence data. To this end, we have cloned and sequenced the cDNA encoding the 57 kDa polypeptide of the Arabidopsis vacuolar membrane H+-ATPase. To our knowledge, this is the first report of the sequence of a "57-kDa" subunit for plant or animal endomembrane H+-ATPase. This cDNA encodes a hydrophilic polypeptide containing a putative ATP binding site. Lack of a secretion signal sequence suggests it is not processed through the endoplasmic reticulum but translated on cytosolic ribosomes. Comparison of protein sequences shows the 57-kDa subunit from Arabidopsis to be nearly identical with the corresponding subunit in Neurospora vacuolar membrane H+-ATPase, very similar to the beta subunit of the archaebacterium Sulfolobus, and slightly, but nevertheless significantly, homologous to the alpha and beta subunits of the F0F1-ATPases. These results suggest that these different classes of ATPases have evolved from a common ancestor. PMID- 2903859 TI - Insertional inactivation of the major autolysin gene of Streptococcus pneumoniae. AB - The lytA gene encoding the major pneumococcal autolysin (N-acetylmuramoyl-L alanine amidase) was inactivated by inserting the 2-kilobase MspI fragment of pE194 containing the staphylococcal ermC gene. Stable autolysis-deficient (Lyt-) mutants and their isogenic Lyt+ parents were used in experiments designed to test possible physiological functions of the amidase. No autolysis could be induced in the mutants grown at 37 degrees C by deoxycholate, by incubation in stationary phase, or by treatment with penicillin. On the other hand, the Lyt- mutants exhibited normal growth rates and yields and normal adaptive responses during shifts from one growth temperature or nutritional condition to another. There was no evidence for impeded cell separation (chain formation). Colonies of Lyt- insertional mutants produced normal hemolytic zones on blood agar; they showed normal (high) levels of competence for genetic transformation. Lyt- mutants were also able to produce type 3 and 6 capsular polysaccharides, and such strains showed the same degree of virulence in mice as did the isogenic Lyt+ parent. The physiological function(s) of the amidase remains a puzzle. PMID- 2903861 TI - The yeast lysyl-tRNA synthetase gene. Evidence for general amino acid control of its expression and domain structure of the encoded protein. AB - The nucleotide sequence of a 3.6-kilobase pair DNA fragment containing the structural gene for yeast cytoplasmic lysyl-tRNA synthetase (KRS1) and its flanking regions was determined. The encoded protein of 67,881 kDa displays a cluster of 11 lysines within a 29-amino acid residue segment at its amino terminal extremity. Evidence is presented that this segment is responsible for the affinity displayed by the native enzyme toward polyanionic carriers. The transcription initiation sites of the KRS1 gene were determined. Upstream from the TATA box, putative control elements corresponding to the concensus sequences for the RPG box and the general amino acid control system were identified. Evidence for transcriptional induction of the KRS1 gene via the general amino acid control system is presented. PMID- 2903863 TI - Lophotoxin and related coral toxins covalently label the alpha-subunit of the nicotinic acetylcholine receptor. AB - Lophotoxin and lophotoxin analog-1 are uncharged cyclic diterpenes obtained from gorgonian corals. They have been shown to block the function of nicotinic acetylcholine receptors. Inhibition results from blockade of the agonist recognition site and appears irreversible in that extensive washing does not restore receptor function. This study was undertaken to determine whether this apparently irreversible inhibition involves covalent labeling at a selective site and to further characterize this site directly. Incubation of membranes prepared from the electric organ of Torpedo californica with analog-1 followed by reduction with NaB3H4 resulted in the incorporation of radioactivity into several membrane proteins. The incorporation of radioactivity into the alpha-subunit of the receptor was blocked by prior incubation with agonists and antagonists. [3H]Lophotoxin and [3H]analog-1 were prepared by reduction with NaB3H4 and back oxidation with CrO3. The radiolabeled coral toxins reacted selectively and covalently with the alpha-subunit of the receptor. Their binding was prevented by prior exposure to agonists and antagonists. In contrast to the site-directed alkylating agent 4-(N-maleimido)benzyltrimethylammonium iodide, prior reduction of the receptor was not required for covalent binding of 3H-labeled coral toxins. Selective reduction of Cys192 and Cys193 followed by alkylation with 4-(N maleimido)benzyltrimethylammonium iodide blocked the binding of [3H]analog-1, whereas alkylation with iodoacetic acid or iodoacetamide did not. Thus, the binding site for the coral toxins does not overlap the binding surface near Cys192 and Cys193. Digestion of isolated labeled alpha-subunits with endoglycosidase H revealed that the polypeptide portion of the protein retained the covalently bound [3H]analog-1. Digestion with staphylococcal V8 protease revealed two major peptides of approximately 19 and 20 kDa, along with several smaller peptides. Only the 20-kDa peptide retained the covalently bound [3H]analog-1, localizing the site of covalent attachment between Ser173 and Glu335. The unique chemical structure and covalent reactivity of these gorgonian coral toxins will undoubtedly allow further insights into the structure of the agonist recognition site. PMID- 2903862 TI - Multiple sterol regulatory elements in promoter for hamster 3-hydroxy-3 methylglutaryl-coenzyme A synthase. AB - Through substitution mutagenesis and gene transfer experiments in cultured cells, we have identified three sequences in the 5' flanking region of the gene for hamster 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) synthase that are required for sterol-mediated regulation of transcription. Point mutations in any one of these sequences largely prevented the increase in transcription that normally follows cellular sterol depletion. These mutations did not alter the low level of transcription that occurs in the presence of sterols. Two of the three sterol regulatory sequences contain an octanucleotide that shows a 7/8-base pair match with a sequence that was previously identified as a sterol regulatory element in the genes for HMG-CoA reductase and the low density lipoprotein receptor, both of which are induced by sterol deprivation. The third sterol regulatory region in the HMG-CoA synthase promoter shows only a low-level match with the other sterol regulatory elements. The current data suggest that the sterol regulatory elements in the HMG-CoA synthase promoter operate by a conditional positive mechanism: in the absence of sterols, regulatory proteins bind to these elements and stimulate transcription; in the presence of sterols, the regulatory proteins are inactivated and transcription decreases to the basal rate. PMID- 2903864 TI - A novel function of glutamine in cell culture: utilization of glutamine for the uptake of cystine in human fibroblasts. AB - Transport and metabolism of glutamine has been investigated in human diploid fibroblasts, IMR-90. Glutamine was taken up via System ASC (Na+-dependent amino acid transport system especially reactive with short or polar side chain amino acids). In the routine culture medium the cells contained a large quantity of glutamate; its major source was shown to be glutamine in the medium. Previously we described a transport system that mediates the entrance of cystine in exchange for the exit of glutamate (Bannai, 1986). Since the cystine taken up is reduced to cysteine and the cysteine readily exits to the medium where it is oxidized to cystine, a cystine-cysteine cycle across the plasma membrane has been postulated. When the cells were cultured in glutamate/glutamine-free medium, intracellular glutamate decreased, depending on the amount of cystine in the medium; in the absence of cystine, glutamate decreased very slowly. When the cells were cultured in ordinary medium, glutamine in the medium decreased, and glutamate in the medium increased. Both changes were well correlated with cystine concentration in the medium. These results are consistent with the view that the intracellular glutamate, of which the source is glutamine in the medium, is released from the cells into the medium in order to take up cystine and thereby to rotate the cystine-cysteine cycle. In the routine culture one-third to one-half of the total consumption of glutamine seems to be used for the uptake of cystine. PMID- 2903865 TI - Effect of reduced protein synthesis on the cell cycle in sea urchin embryos. AB - We have reinvestigated the existence of cyclical fluctuations of protein synthesis and have examined the effects of reducing it in early embryos of the purple sea urchin, Strongylocentrotus purpuratus. The results show that protein synthesis increases linearly during the first 45-60 minutes after fertilization, then transiently decreases during mitosis, and rises again at first cleavage. Reducing protein synthesis of embryos to 35% its normal value only slightly affects the rate of progression through the cell cycle. It is also shown that the observed retardations of the cell cycle, under depressed protein synthesis, are attributable (by 80%) to a lengthening of the premitotic phase but also, to a lesser extent (20%), to a lengthening of the mitotic phase itself. These results suggest that mitotic proteins, in sea urchin embryos, are stable and little affected by an imposed decrease of protein synthesis during their accumulation phase. This analysis supports the view that specific mechanisms, other than decreased protein synthesis, need be turned on only at appropriate times during the cell cycle in order to explain the destruction or deactivation of mitotic proteins. Finally, a one-dimensional SDS-PAGE analysis of synthesized proteins, labeled with 35S-methionine, reveals the presence of a 50-kDa cyclin showing the expected characteristics of mitotic proteins deduced from our results. PMID- 2903866 TI - Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion. AB - To determine how arginine (Arg) stimulates GH secretion, we investigated its interaction with GHRH in vivo and in vitro. Six normal men were studied on four occasions: 1) Arg-TRH, 30 g arginine were administered in 500 mL saline in 30 min, followed by an injection of 200 micrograms TRH; 2) GHRH-Arg-TRH, 100 micrograms GHRH-(1-44) were given iv as a bolus immediately before the Arg infusion, followed by 200 micrograms TRH, iv; 3) GHRH test, 100 micrograms GHRH were given as an iv bolus; and 4) TRH test, 200 micrograms TRH were given iv as a bolus dose. Blood samples were collected at 15-min intervals for 30 min before and 120 min after the start of each infusion. Anterior pituitary cells from rats were coincubated with Arg (3, 6, 15, 30, and 60 mg/mL) and GHRH (0.05, 1, 5, and 10 nmol/L) for a period of 3 h. Rat GH was measured in the medium. After Arg-TRH the mean serum GH concentration increased significantly from 0.6 to 23.3 +/- 7.3 (+/- SE) micrograms/L at 60 min. TRH increased serum TSH and PRL significantly (maximum TSH, 11.1 +/- 1.8 mU/L; maximum PRL, 74.6 +/- 8.4 micrograms/L). After GHRH-Arg-TRH, the maximal serum GH level was significantly higher (72.7 +/- 13.4 micrograms/L) than that after Arg-TRH alone, whereas serum TSH and PRL increased to comparable levels (TSH, 10.2 +/- 3.0 mU/L; PRL, 64.4 +/- 13.6 micrograms/L). GHRH alone increased serum GH to 44.9 +/- 9.8 micrograms/L, significantly less than when GHRH, Arg, and TRH were given. TRH alone increased serum TSH to 6.6 +/- 0.6 mU/L, significantly less than the TSH response to Arg-TRH. The PRL increase after TRH only also was lower (47.2 +/- 6.8 micrograms/L) than the PRL response after Arg-TRH. In vitro Arg had no effect on basal and GHRH-stimulated GH secretion. Our results indicate that Arg administered with GHRH led to higher serum GH levels than did a maximally stimulatory dose of GHRH or Arg alone. The serum TSH response to Arg-TRH also was greater than that to TRH alone. We conclude that the stimulatory effects of Arg are mediated by suppression of endogenous somatostatin secretion. PMID- 2903867 TI - Altered expression and function of the insulin receptor in a family with lipoatrophic diabetes. AB - To determine the role of genetic defects in the insulin receptor in the insulin resistance of lipoatrophic diabetes mellitus, we studied insulin binding, insulin receptor autophosphorylation, and insulin receptor mRNA levels and performed Southern blot analysis of genomic DNA in four siblings, all of whom have some degree of insulin resistance and three of whom have lipoatrophy. The insulin receptor concentration in Epstein-Barr virus-transformed lymphocytes was about 30% of normal in all three lipoatrophic siblings (LA1, LA2, and LA3) and was 55% of normal in the nonlipoatrophic sibling (LAS). Insulin receptor mRNA concentrations in the lymphocytes paralleled insulin binding and ranged from 15 67% of the mean normal level. Insulin binding to fibroblasts was also reduced about 50% in the lipoatrophic siblings. In addition, insulin binding to fibroblasts of LAS and LA2 exhibited a rightward shift of the competition curve, suggesting reduced receptor affinity [ED50, 35 and 50 ng/mL (5845 and 8350 pmol/L); normal, 1-3 ng/mL (167-501 pmol/L)]. Receptor autophosphorylation determined using Triton X-100 extracts of the fibroblasts was decreased in LA1 and LA3, but normal in LA2 and LAS. Using restriction enzyme digests of genomic DNA and probes spanning the entire cDNA of the insulin receptor, no gross alterations in receptor gene structure were detected in any members of this family. In 2 of the lipoatrophic siblings (LA1 and LA3) and in the sibling with insulin resistance but no lipoatrophy (LAS), a unique variant BamHI site was detected using a probe to the alpha-subunit region. This site was not found in 200 normal or diabetic insulin receptor alleles. By use of probes 5' and 3' to the alpha-subunit probe and by genomic cloning analysis, this variant BamHI site was localized to an intron in the insulin receptor gene downstream of exon 3 which encodes amino acids 191-296 of the alpha-subunit of the receptor. These data indicate the complex nature of familial lipoatrophic diabetes mellitus, with alterations in insulin receptor expression and/or function in both clinically affected and non-affected siblings. Both the reduced insulin binding and reduced levels of insulin receptor mRNA in the lipoatrophic siblings suggest that an insulin receptor gene defect contributes to this syndrome. Several members of this family also carry a unique variant insulin receptor gene, which, however, could not be linked to a specific alteration in receptor expression or the presence of lipoatrophy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903868 TI - Two types of tyrosine hydroxylase-immunoreactive amacrine cell in the rhesus monkey retina. AB - Two types of amacrine cell immunoreactive for tyrosine hydroxylase (TH), the rate limiting enzyme in the catecholamine (CA)-synthetic pathway, are described in the rhesus monkey retina with the indirect-immunofluorescent method. These 2 types of neuron differ in soma size, plane of arborization in the inner plexiform layer, levels of the enzyme TH as quantified by microspectrofluorometry, and population density. Type 1 CA cells have comparatively large cell bodies almost exclusively in the innermost row of the inner nuclear layer; their processes arborize in the outermost stratum of the inner plexiform layer; they give rise to fine predominantly radially oriented fibers in the inner nuclear layer; and there are about 26 type 1 CA cells/mm2. Type 2 CA amacrine cells have relatively small cell bodies located in the inner nuclear layer (44.4%), the inner plexiform layer (35.6%) and the ganglion cell layer (20%), and their processes arborize in the center of the inner plexiform layer. Although type 2 CA amacrine cells are more numerous (35 cells/mm2) than type 1 CA cells, type 1 CA amacrine cells are 3.5 x brighter than type 2 CA cells and therefore likely to contain 3.5 X more TH. Thus the primate retina contains 2 distinct catecholaminergic neuronal pathways that could have different functional roles in vision. PMID- 2903869 TI - Catecholaminergic and cholinergic neurons in the developing retina of the rat. AB - We have examined the development of catecholaminergic and cholinergic neurons in the retina of the rat by using antibodies against the enzymes tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT), respectively. TH immunoreactivity was first detected at P (postnatal day) 3 in somata located in the inner part of the cytoblast layer (CBL) and in fine dendrites extending toward the middle of the inner plexiform layer (IPL). These cells were similar in shape and soma size to the class 2 TH-immunoreactive (TH-IR) cells of the adult rat. At P6, TH-immunoreactivity was expressed by a second population of cells. Their somata were in the inner part of the inner nuclear layer (INL), but were distinctly larger, with short thick dendrites extending into the outer and/or middle parts of the IPL. Over subsequent days, the dendrites of these larger cells spread profusely in the outer part of the IPL, making it likely that they are the class 1 TH-IR cells of the adult. ChAT-immunoreactive (ChAT-IR) cells were not detected until P15, when ChAT-IR somata were observed in the ganglion cell layer (GCL) and INL, and their dendrites were observed already segregated into the distinct strata of the IPL in which they are found in the adult. The subsequent growth of TH-IR somata of both classes was uneven, persisting longer in temporal than in nasal retina. This extended growth of temporal cells establishes the marked nasotemporal differences in soma diameter apparent among TH-IR cells in the adult (Mitrofanis and Stone, '86; Mitrofanis et al., '88b). The growth and adult size of ChAT-IR somata, on the other hand, did not vary with retinal position; their diameters were similar to those of the adult cells from the time they first appeared. The distribution of ChAT-IR cells at P15 shared several features of the distribution of ganglion cells. The density of ChAT-IR cells was greatest at the area of peak ganglion cell density and declined toward the periphery. In contrast, TH-IR cells concentrated from the time they first appeared at the superior temporal margin, peripheral to the area of peak density of ganglion and ChAT-IR cells. PMID- 2903870 TI - Distribution of opioid peptides in the preoptic region: immunohistochemical evidence for a steroid-sensitive enkephalin sexual dimorphism. AB - The distribution of cells and fibers that contain opioid peptides within the preoptic region of the rat was examined immunohistochemically. Cells and/or fibers that contain peptides derived from each of the three major opioid peptide families were differentially stained by using antisera that recognize unique derivatives of each precursor molecule and do not cross-react with members of the other opioid peptide families. A beta-endorphin (beta E) antiserum was used to stain fibers that contain peptides derived from the proopiomelanocortin molecule, and dynorphin-containing cells were identified by using an antiserum directed toward dynorphin B (Dyn B) that does not show detectable cross-reactivity with enkephalin-related peptides. An antiserum raised against peptide E (PE), which does not appear to cross-react significantly with dynorphin peptides, was used to localize enkephalin cells and fibers. Each family of opioid peptides showed a unique distribution in the preoptic region. beta E-immunoreactive fibers were primarily localized to the preoptic part of the periventricular nucleus, with moderate densities of fibers contained in the anteroventral periventricular nucleus (AVPv) and medial preoptic nucleus (MPN). Dyn B-immunoreactive fibers showed a somewhat more uniform distribution throughout the region, and only a few Dyn B-stained cells bodies were found within the medial preoptic area. In contrast, the preoptic region contained hundreds of PE-immunoreactive cells, which were particularly numerous within the AVPv, MPN, and anterodorsal preoptic nucleus. The AVPv and MPN also contained discretely localized plexuses of PE stained fibers. Although the overall distributions of opioid peptide-containing fibers within the preoptic region were quite similar in male and female rats, differential distributions of fibers were found in certain nuclei such as the AVPv and MPN, and they were correlated with previously identified cytoarchitectonic sexual dimorphisms. Such differential distributions were particularly distinct for enkephalin-containing fibers. Although the AVPv is larger in female rats, it contained more PE-immunoreactive cell bodies in male rats, and we have shown here that this sexual dimorphism appears to be at least partially dependent on perinatal levels of gonadal steroids. In contrast, no difference in the number of PE-stained cells was found within the anterodorsal preoptic nucleus of male and female animals, indicating that sexual differences are not a general characteristic of enkephalinergic cells in the preoptic region of the rat.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2903871 TI - Beta-blocking drugs and psoriasis. A review of cutaneous side effects and retrospective analysis of their effects on psoriasis. AB - beta-Adrenergic receptor blockers have been prescribed widely since their introduction 20 years ago. Noncardiac indications for beta-blockers have been expanded. Dermatologic manifestations of beta-blockers are reviewed in conjunction with their more liberal use. A retrospective analysis of our experience with beta-blockers in patients with psoriasis is presented. A 1-year study of 588 psoriatic patients who received treatment revealed that 26 patients were taking beta-blockers. Exacerbations of psoriasis were noted in 72.4% of these patients. beta-Blockers may worsen psoriasis and should be carefully evaluated in the management of these patients. PMID- 2903872 TI - Chronic urticaria: review of nonsedating H1 antihistamines in treatment. AB - Antihistamines are the drugs of choice in the symptomatic relief of chronic urticaria; however, the usefulness of classic antihistamines has been limited by side effects, especially daytime sedation. In the 1980s a new class of antihistamines has been developed that maintains effectiveness and produces less sedation. This review analyzes each of the new nonsedating antihistamines and evaluates its clinical efficacy, safety, and convenience in the treatment of chronic urticaria. PMID- 2903873 TI - Antiarrhythmic effects of alpha-adrenoceptor antagonists in guinea pig ventricular myocardium. AB - Antiarrhythmic effects of alpha-adrenoceptor antagonists were assessed in the reserpinized guinea pig ventricular myocardium. Both bunazosin (1 to 3 x 10(-7) M), a new alpha 1-adrenoceptor antagonist, and yohimbine (1 to 3 x 10(-7) M), another adrenoceptor antagonist, suppressed the transient depolarization and triggered activity induced by a train of rapid stimuli in the solution containing low potassium ion (K+), high calcium ion (Ca2+) and strophanthidin (1 to 5 x 10( 7) M). Bunazosin (3 x 10(-6) M) abolished the facilitatory effect of hypoxia on beta-adrenoceptor mediated abnormal automaticity. To clarify the mechanisms underlying the antiarrhythmic properties of alpha-adrenoceptor antagonists, their electrophysiologic effects on the fast and slow action potentials were investigated. Alpha-adrenoceptor antagonists (bunazosin, yohimbine and phentolamine) suppressed the slow response in a dose-related manner. The voltage dependent block and use-dependent block of the maximal rate of rise (Vmax) of action potentials by bunazosin (10(-5) to 10(-4) M) and yohimbine (10(-6) to 10( 5) M) were studied. The analysis of the onset and recovery kinetics from the use dependent block of drugs showed that both bunazosin and yohimbine act as slow kinetic drugs. It is concluded that alpha-adrenoceptor antagonists seem to have an antiarrhythmic effect through the inhibition of fast sodium ion (Na+) and slow Ca2+ currents of the cell membrane independently of blockade of myocardial alpha adrenoceptors. PMID- 2903874 TI - Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2.ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. AB - 17,187 patients entering 417 hospitals up to 24 h (median 5 h) after the onset of suspected acute myocardial infarction were randomized, with placebo control, between i) a 1 h intravenous infusion of 1.5 million units of streptokinase; ii) 1 month of 160 mg/day enteric-coated aspirin; iii) both active treatments; or iv) neither. Streptokinase alone and aspirin alone each produced a highly significant reduction in 5 week vascular mortality: 791/8592 (9.2%) vascular deaths among patients allocated streptokinase infusion versus 1029/8595 (12.0%) among those allocated placebo infusion (odds reduction: 25% +/- 4; 2p less than 0.00001); 804/8587 (9.4%) vascular deaths among patients allocated aspirin tablets versus 1016/8600 (11.8%) among those allocated placebo tablets (odds reduction: 23% +/- 4; 2p less than 0.00001). The combination of streptokinase and aspirin was significantly (2p less than 0.0001) better than either agent alone. Their separate effects on vascular death appeared to be additive: 343/4292 (8.0%) among patients allocated both active agents versus 568/4300 (13.2%) among those allocated neither (odds reduction: 42% +/- 5; 95% confidence limits 34% to 50%). There was evidence of benefit rom each agent even for patients treated late after pain onset (odds reduction at 0-4, 5-12, and 13-24 h: 35% +/- 6, 16% +/- 7 and 21% +/- 12 for streptokinase alone; 25% +/- 7,21% +/- 7 and 21% +/- 12 for aspirin alone; and 53% +/- 8,32% +/- 9 and 38% +/- 15 for the combination of streptokinase and aspirin). Streptokinase was associated with an excess of bleeds requiring transfusion (0.5% versus 0.2%) and of confirmed cerebral hemorrhage (0.1% versus 0.0%), but with fewer other strokes (0.6% versus 0.8%). These "other" strokes may have included a few undiagnosed cerebral hemorrhages, but still there was no increase in total strokes (0.7% streptokinase versus 0.8% placebo infusion). Aspirin significantly reduced nonfatal reinfarction (1.0% versus 2.0%) and nonfatal stroke (0.3% versus 0.6%), and was not associated with any significant increase in cerebral hemorrhage or in bleeds requiring transfusion. An excess of nonfatal reinfarction was reported when streptokinase was used alone, but this appeared to be entirely avoided by the addition of aspirin. Those allocated the combination of streptokinase and aspirin had significantly fewer reinfarctions (1.8% versus 2.9%), strokes (0.6% versus 1.1%), and deaths (8.0% versus 13.2%) than those allocated neither.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903875 TI - Anaphylaxis to muscle relaxants: cross-sensitivity studied by radioimmunoassays compared to intradermal tests in 34 cases. AB - Thirty-four patients (31 female and three male patients) with a previous anaphylactoid shock to muscle relaxants were investigated. The seric antimyorelaxant IgE was detected by radioimmunoassay (RIA), and the results were compared to intradermal test (IDR) reactions to dilutions of the commercial drugs. The RIA was carried out with a Sepharose-myorelaxant solid phase and anti IgE 125I-labeled IgG. The results corresponded to the percentage of labeled anti IgE bound on the solid phase. The RIA with Sepharose-alcuronium and Sepharose choline was estimated positive from determination with normal sera (n = 12) when bound IgE was greater than 1.0% and 1.5%, respectively. The RIA and IDR were positive in 43.5% and 75%, respectively, of the cases, with a concordance of 66%. One test at least was positive in 79.4% of the cases. No correlation was found between IgE seric levels and the RIA nor between the cutaneous sensitivity and the RIA. Cross-reactivity with Sepharose-choline and Sepharose-alcuronium was observed in 50%, and it was demonstrated by IDR in only 34.2%. The RIA demonstrated the specificity of IgE to quaternary ammonium compounds as myorelaxant drugs. The positive IDR revealed the bridging of mast cell-bound specific IgE, depending on structural conditions, such as the flexibility of the molecules or the variable specificity of the antibodies, restricted to quaternary ammonium ions or enlarged to a broader part of the incriminated molecules. PMID- 2903876 TI - Duration of the suppressive effect of tricyclic antidepressants on histamine induced wheal-and-flare reactions in human skin. AB - The antihistaminic properties of the tricyclic antidepressants have been recognized since these compounds were first developed. Antidepressants, which are equally effective for treating depression or used in the treatment of chronic urticaria, have varying in vitro antihistaminic properties. We compared the duration of H1-receptor blockade by two tricyclic antidepressants, doxepin (the most potent antihistamine) and desipramine (the least potent antihistamine), in a single dose, double-blind, noncrossover study. After baseline prick test with histamine phosphate 1:1000 by Multitest (Lincoln Diagnostics, Decatur, Ill.), the suppression of cutaneous histamine-induced wheal-and-flare responses were measured daily for 7 days in 33 healthy volunteers who were randomly administered a single 25 mg dose of oral desipramine or doxepin. Significant differences in the suppression of the wheal-and-flare responses to histamine between the two drugs were noted (p less than 0.05) during the first 3 days. Desipramine suppressed the wheal for 2 days and flare for 1 day. Doxepin suppressed the wheal for 4 days and flare for 6 days. Our results suggest doxepin should be withheld for at least 7 days before allergy skin testing. PMID- 2903877 TI - New directions and dimensions in the treatment of allergic rhinitis. AB - Physicians who treat patients with allergic rhinitis have a number of therapeutic options, including antihistamines, decongestants, cromolyn, anticholinergics, corticosteroids, and immunotherapy. Antihistamines are widely used for the treatment of mild allergic rhinitis and are often effective, although more severe cases will require other medications. The newer antihistamines may induce less drowsiness, which is the most prominent side effect of the older antihistamines. Topical nasal decongestants give fast relief from nasal congestion, but their overuse may result in rebound congestion. Because their efficacy in allergic rhinitis is variable, oral decongestants are usually used in combination with antihistamines. Nasal cromolyn is effective for many patients with allergic rhinitis, but its effect is variable and it is useful in severe allergic rhinitis. PMID- 2903878 TI - Effects of potassium channel-blocking agents on neurons in the inferior mesenteric ganglion in guinea-pig. AB - Intracellular recordings were made from neurons (n = 121) in the inferior mesenteric ganglion (IMG) in guinea-pig. The pharmacological actions of 4 aminopyridine (4-AP), barium ions (Ba2+) and tetraethylammonium ions (TEA) were studied on IMG cells which received an excitatory, cholinergic input from mechanosensory nerves in the gastrointestinal tract. 4-AP mediated an excitatory action which involved two separate effects. Firstly, 4-AP increased the incidence of spontaneously occurring, fast EPSPs which gave rise to a spontaneous discharge of action potentials. This indirect, excitatory effect was attributed to an increase in the spontaneous release of acetylcholine from excitatory nerves to the IMG. Secondly, 4-AP altered the excitability of IMG cells and brought about burst discharges and continuous discharges of action potentials. This direct, excitatory effect was not dependent on the spontaneous release of acetylcholine; instead, it was attributed to the blockade of a potassium current similar to the A-current (IA). The excitatory action of Ba2+ also involved two separate effects. Firstly, Ba2+ increased the incidence of spontaneously occurring, fast EPSPs which gave rise to a spontaneous discharge of action potentials. This indirect, excitatory effect was interpreted as Ba2+ mimicking the actions of Ca2+ to facilitate the spontaneous release of acetylcholine. Secondly, Ba2+ altered the excitability of IMG cells and brought about a continuous discharge of action potentials. This excitatory effect was attributed to the blockade of a potassium current similar to the M-current (IM). TEA exerted an excitatory, then inhibitory, action on IMG cells. Initially, TEA brought about the continuous discharge of action potentials; firing gradually arrested as IMG cells depolarized slowly and a depolarizing block of excitation (i.e. inhibition) developed. The block on excitation was relieved by first restoring the resting membrane potential of IMG cells with hyperpolarizing current-clamp. Thereafter, action potentials were elicited by anode-break excitation by temporarily removing the hyperpolarizing current-clamp. The durations of action potentials and afterspike hyperpolarizations were prolonged in the presence of TEA. The effect of TEA on the action potential of IMG cells was attributed to the blockade of the delayed rectifier (IK). The effect on the afterspike hyperpolarization was considered the indirect consequence of a blockade of IK; it allowed the development of an inward calcium current which enhanced the calcium-activated, potassium current (IKCa) mediating afterhyperpolarizations. PMID- 2903880 TI - The undertreatment of pain. PMID- 2903879 TI - Afterspike-hyperpolarization of neurons in the inferior mesenteric ganglion in guinea-pig. AB - Intracellular recordings were made from neurons (n = 121) in the inferior mesenteric ganglion (IMG) in guinea-pig. The afterspike hyperpolarization (ASH) following a single action potential was studied in IMG cells which received an excitatory, cholinergic innervation from mechanosensory nerves in the gastrointestinal tract. The amplitude of ASH was dependent on the membrane potential of IMG cells and the concentration of K+ in the bathing solution. The reversal potential of ASH (-80- -90 mV, in normal Krebs solution) appeared to follow the equilibrium potential for K+, as [K+]o was changed, suggesting that ASH was the product of K+-efflux. Further evidence suggested that a major component of the K+-efflux was dependent on the concentration of Ca2+ in the bathing medium. Elevation and reduction of [Ca2+]o increased and decreased, respectively, the amplitude and duration of ASH. In the presence of tetrodotoxin, depolarizing current pulses elicited spike-like events which (1) were dependent on [Ca2+]o and the degree of depolarization by current-clamp and (2) were followed by afterhyperpolarizations that were also dependent on [Ca2+]o and degree of depolarization by current-clamp. In the combined presence of tetrodotoxin and tetraethylammonium, depolarizing current pulses elicited prolonged action potentials (up to 100 ms in duration) followed by prolonged ASH (up to 3 s in duration). Spike-like events, prolonged action potentials and their afterhyperpolarizations were reduced in amplitude and duration when the calcium channel blocking ion, Co2+, or blocking drug, verapamil, was present in the bathing medium. In normal Krebs solution, the ASH of action potentials produced by nerve stimulation was reduced but not abolished in the presence of Co2+. These results suggested that Ca2+ entered IMG cells during depolarization and activated the K+-conductance mechanisms responsible for the ASH. However, an initial component of the ASH may have involved other voltage-dependent K+-currents known to be activated during the excitation of sympathetic neurons. The amplitude and duration of ASH differed during non-synaptic and synaptic excitation of IMG cells, and differed when action potentials resulted from fast and slow EPSPs. In addition, the amplitude and duration of ASH were altered by noradrenaline, by the cholinomimetic, carbachol, and by 3 neuropeptides present in the IMG, namely leucine-enkephalin, substance P and vasoactive intestinal polypeptide.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2903882 TI - Induction and removal of DNA interstrand cross-links in V-79 Chinese hamster cells measured by hydroxylapatite chromatography after treatments with bifunctional furocoumarins. AB - DNA interstrand crosslinks (CL) photoinduced by bifunctional furocoumarins in V 79 Chinese hamster cells were measured by alkaline denaturation and hydroxylapatite chromatography. Treatments with 5-methoxypsoralen (5-MOP), 8 methoxypsoralen (8-MOP) and 4,5',8-trimethylpsoralen (4,5',8-TMP) and 365 nm irradiation (UVA) confer a dose-dependent linear increase in the amount of double stranded DNA indicating the induction of CL. Determination in alkaline sucrose gradients of the molecular weight of the DNA and estimation of drug-induced strand breakage allowed quantification of the CL induced. 5-MOP was found to be slightly more effective than 8-MOP whereas 4,5',8-TMP was 9 times more effective for the induction of CL. The fate of CL during post-treatment incubation was also followed. Cells in exponential growth phase were found to be efficient in the removal of CL. PMID- 2903881 TI - Reovirus type 3 and [125I]-iodocyanopindolol bind to distinct domains on the beta adrenergic like receptor. AB - Antireceptor antibodies have been developed as a probe to study the cellular receptor for reovirus type 3. Using this probe, a glycoprotein with a molecular weight of 65-67 kilodaltons and a pI of 5.8-6.0 was isolated and identified as the reovirus receptor. This protein was also structurally similar to the affinity purified beta-adrenergic receptor from calf lung. In this report, we employ [125I]-iodocyanopindolol, a high affinity beta-adrenergic antagonist, to further characterize this protein. We show that R1.1, a murine thymoma cell line, possesses about 2,000 receptors per cell with high affinity for ICYP (kD = 3.3 X 10(-11) M). Competitive inhibition studies suggest that the receptor is of the beta-2 subtype. Solubilized receptor proteins from R1.1 cells bound to the antireceptor antibody were further purified by SDS-PAGE and electroelution from the gel. Five percent of the proteins thus obtained could bind ICYP with high affinity (kD = 1.6 X 10(-10) M). This suggests that the purification procedure produced a collection of forms of this 65- to 67-kilodalton protein, some of which retained the conformation for binding the beta ligands. We also demonstrate that the isolated receptor protein was able to bind ICYP even when the virus binding site was occupied by the anti-idiotype, suggesting that reovirus type 3 and the beta ligands bind to distinct domains on the receptor protein. PMID- 2903883 TI - Cell survival and DNA double-strand break repair following X-ray or neutron irradiation of V79 cells. AB - We have investigated the effects of 250kVp X-rays and 2.3 MeV (mean energy) neutrons on the cell survival, DNA double-strand break (dsb) induction and repair (using the Kohn neutral elution technique) in V79 cells. The lethal effects of neutrons were shown to be significantly greater than for a similar dose of X-rays (RBE = 3.55 at 10 per cent survival). However, the RBE for dsb induction, in a dose range of 10-50 Gy, was 1. On investigating the repair of DNA dsb induced by either X-ray or neutron irradiation, clear differences in the pattern of repair were found. Both a fast and a slow component of repair were seen in both cases; the former, however, was reduced following neutron irradiation and, since the amount of slow repair was similar in both cases, this resulted in proportionally more unrejoined breaks after neutrons. These experiments were carried out with elution buffer at pH 9.6; however, when similar experiments were performed at pH 7.2 the results obtained support our earlier findings. We suggest that these differences in DNA dsb repair reflect basic differences in the nature of the lesions induced by high- and low-LET ionizing radiations. PMID- 2903884 TI - Reduced pH increases recovery from radiation damage potentially leading to cell death and to in vitro transformation. AB - C3H-10T1/2 cells were grown to plateau phase and assessed for recovery from radiation damage under acidic and normal pH conditions. Repair of potentially lethal damage (PLD) was observed after X-ray doses of 5.0, 6.0 and 12.0 Gy and repair increased with dose. The repair at an acidic pH of 6.8 was greater than at the normal pH of 7.4. Repair of potentially transforming damage (PTD) was also observed when cells were held in plateau phase after irradiation. Repair of PTD was greater at the acidic pH than at the normal pH. When PTD recovery was plotted vs PLD recovery the results showed a good linear correlation with approximately twice as much PTDR. The experimental conditions allowing PLDR and PTDR indicate that the repair process may be error-free, since transformation was reduced in all experiments which showed recovery from PLD. PMID- 2903885 TI - The doubling time of regenerating clonogenic cells in the crypts of the irradiated mouse small intestine. AB - The number of clonogenic cells per intestinal crypt has been estimated in control and gamma-irradiated mice, from the response to a single or two test doses. Control unirradiated mice contained 43 +/- 8 clonogenic cells per crypt, which was reduced to about 3 per crypt immediately after 8.0 Gy. After a mitotic delay which was approximately 18 h or 2.25 h/Gy the number of clonogenic cells per crypt increased exponentially with a doubling time of 21 +/- 4 h to reach the control values by about the 4th day postirradiation. The growth curve was related to the changes in total cellularity and the cell production rate per crypt. Since both of these rise during the period of clonogenic regrowth some clonogenic cells must be diverted into the dividing transit cell population, so that the cell cycle time will be shorter than the doubling time given above. PMID- 2903886 TI - Use of restriction endonucleases to study relationships between DNA double-strand breaks, chromosomal aberrations and other end-points in mammalian cells. AB - Some of the cellular effects of radiation, such as mutations, chromosomal aberrations and cell killing, can be mimicked by inducing 'pure' double-strand breaks (dsb) in DNA of cells with restriction endonucleases (RE), although the chemical structure of the ends of dsb induced by RE are likely to differ from those induced by X-rays. Chromosomal aberrations are induced by treatment of cells with a variety of RE at all stages of the cell cycle. The frequency with which RE induce dsb in the DNA may be one factor determining the number of aberrations induced. However, the structure of the dsb generated may also determine the frequencies of aberrations induced. RE which generate 'cohesive ended' dsb in the DNA have been shown to induce lower frequencies of aberrations than those causing 'blunt-ended' dsb, when inactivated Sendai virus is used to permeabilize cells. Other methods, involving a hypertonic shock to the treated cells, have led to results in which there is little or no difference in the effectiveness between the two types of dsb. It is argued here that the use of treatments which cause a hypertonic shock may influence the frequencies of aberrations induced. PMID- 2903887 TI - Lack of dose-rate effect for mutation induction by gamma-rays in human TK6 cells. AB - Survival and mutation induction in a human lymphoblastoid cell line ('TK6'), after acute X- and low dose rate continuous gamma-irradiation, were investigated using the hypoxanthine guanine phosphoribosyl transferase (HGPRT)- and the thymidine kinase (TK)-mutation assay. The surviving fraction after acute exposure decreased exponentially (D0 = 0.47 Gy). The HGPRT- and TK-mutation frequencies after acute X- and continuous gamma-irradiation (2.7 and 27 mGy/h) showed linear responses and no dose-rate dependence. PMID- 2903888 TI - Survival of human diploid skin fibroblasts from normal individuals after X irradiation. AB - The cytotoxic effect of X-rays was measured by a colony formation assay in multiple experiments with fibroblast cell strains derived from 24 presumably normal individuals, received as 65 different coded and blinded samples. Each strain was received on two or more occasions at different times and bearing different codes. The means and standard deviations of the survival curve parameters for the 24 strains were: D0 = 123 +/- 23; D10 = 273 +/- 42 cGy. The D0 ranged from 89 to 175 and the D10 from 196 to 372 cGy. The degree of interexperimental variation, though generally minimal, differed considerably among cell strains. There was no systematic effect of passage level, cloning efficiency, serum lot, age or sex of the donor on X-ray survival. These results confirm that the intrinsic radiosensitivity varies significantly among skin fibroblasts isolated from clinically normal individuals, apparently owing to as yet unidentified genetic factors. PMID- 2903889 TI - Comparative human cellular radiosensitivity: I. The effect of SV40 transformation and immortalisation on the gamma-irradiation survival of skin derived fibroblasts from normal individuals and from ataxia-telangiectasia patients and heterozygotes. AB - We have compared cell killing following 60Co gamma irradiation in 22 primary human fibroblast strains, nine SV40-immortalized human fibroblast lines and seven SV40-transformed pre-crisis human fibroblast cultures. We have examined material from normal individuals, from ataxia-telangiectasia (A-T) patients and from A-T heterozygotes. We have confirmed the greater sensitivity of A-T derived cells to gamma radiation. The distinction between A-T and normal cells is maintained in cells immortalized by SV40 virus but the immortal cells are more gamma radiation resistant than the corresponding primary fibroblasts. Cells transformed by plasmids (pSV3gpt and pSV3neo) expressing SV40 T-antigen, both pre- and post crisis, show this increased resistance, indicating that it is expression of SV40 T-antigen, rather than immortalization per se which is responsible for the change. We use D0, obtained from a straight line fit, and D, estimated from a multitarget curve, as parameters to compare radiosensitivity. We suggest that both have their advantages; D0 is perhaps more reproducible, but D is more realistic when comparing shouldered and non-shouldered data. PMID- 2903890 TI - Comparative human cellular radiosensitivity: II. The survival following gamma irradiation of unstimulated (G0) T-lymphocytes, T-lymphocyte lines, lymphoblastoid cell lines and fibroblasts from normal donors, from ataxia telangiectasia patients and from ataxia-telangiectasia heterozygotes. AB - We have measured clonal survival following gamma-irradiation of unstimulated (G0) T-lymphocytes from 35 donors, of 11 T-lymphocyte cell lines, of six lymphoblastoid cell lines, and of nine primary fibroblast strains for which we have G0 T-lymphocyte material from the same donor. Amongst the G0 lymphocytes we have results from nine normal donors, from eight cord bloods, from seven ataxia telangiectasia (A-T) patients and from nine A-T heterozygotes. Although there is some variation between samples, G0 T-lymphocytes from normal donors appear to be slightly more radioresistant than T-lymphocyte lines, with a more shouldered survival curve. From our limited sample, lymphoblastoid cell lines appear to be slightly more radiosensitive than T-lymphocytes. The overall radiosensitivity of primary fibroblasts appears to be broadly similar to that of G0 T-lymphocytes. In nine instances, five A-Ts and four A-T heterozygotes, both G0 T-lymphocytes and primary fibroblasts from the same donor were tested. In five cases there was closely similar radiosensitivity in the two cell types, but in four cases there was some discrepancy. Further work, especially with normal donors, will be required in order to establish how reliably radiosensitivity in other cell types can be predicted from that of G0 T-lymphocytes. In all cell types the hypersensitivity of A-T cells was confirmed. Furthermore, the marginally greater sensitivity of A-T heterozygotes, when compared as a group with normals, was confirmed with G0 T-lymphocytes. Our results also suggest a slightly increased radiosensitivity in G0 T-lymphocytes from some, but not all, cord blood samples. PMID- 2903891 TI - Radiosensitive human tumour cell lines may not be recovery deficient. AB - Split-dose studies have been performed on four human tumour cell lines of widely differing radiosensitivity in order to characterize the relationship between cellular recovery and radiation dose. Previous studies using the split-dose experiment have usually measured recovery at a single dose level and assumed an underlying multi-target model of radiation effect. This predicts that the recovery ratio should reach a plateau when the dose used per fraction is beyond the shoulder of the acute survival curve. In contrast, the linear-quadratic model predicts that the recovery ratio will increase steeply as a function of dose and will never reach a plateau. Our results show that recovery increases with increasing dose and therefore no single value of the recovery ratio can be used for comparative purposes. Using these data, we have derived a value for the beta component of the linear-quadratic model that is independent of alpha. In addition we propose that the beta-parameter derived in this way provides the most satisfactory basis for intercomparison of cellular recovery between cell lines of differing radiosensitivity. Cellular recovery at any given dose was greatest in the most radiosensitive cell line, suggesting that increased radiosensitivity does not result from decreased recovery capacity. The results suggest that cells with steep acute radiation survival curves and which show little split-dose recovery may not be recovery deficient. Consequently, using such cells in attempts to correlate recovery with the underlying molecular processes of radiation damage repair could lead to misleading results. PMID- 2903892 TI - Free radical formation and cell lysis induced by ultrasound in the presence of different rare gases. AB - The effect of varying the temperature of cavitation bubbles in aqueous solutions of different rare gases on free radical formation and shearing stress induced by ultrasound was investigated. After sonication with 50kHz ultrasound the yield of hydroxyl radicals was measured by spin trapping with 5,5-dimethyl-1-pyrroline-N oxide and the cell lysis of cultured mammalian cells was investigated. The hydroxyl radical yields were in the order Xe greater than Kr greater than Ar greater than Ne greater than He, in accord with the higher temperatures of the cavitation bubbles. However, cell lysis induced by shearing stress was the same for all of the rare gases, and independent of their thermal conductivity and the temperature of the cavitation bubbles. PMID- 2903893 TI - ESR/ENDOR study of guanine.HCl.2H2O X-irradiated at 20K. AB - Single crystals of guanine hydrochloride dihydrate, in which the guanine base is protonated at N7, were X-irradiated at 20K, 65K and 150K. Study with K-band ESR and ENDOR techniques indicated at least four radical species to appear in the temperature range 20-300K. Three of the radical species (Radicals 1, 2, and 3) were present immediately following irradiation at 20K. Radical 1 was identified as the molecular anion protonated at O6. Hyperfine couplings in Radical 1 to HC8, HN1, and HN7 were fully characterized with ENDOR spectroscopy. The data indicated this product to be trapped in four different conformations which coalesced into the most stable form as the sample temperature was raised to ca. 180K. Radical 2 was the C8 H-addition radical. For this radical, hyperfine couplings to HN7, HN9, and the two beta-methylene protons were fully characterized with ENDOR spectroscopy. Radical 3 was the result of hydroxyl addition to C8 of the guanine base. For Radical 3, full characterization by ENDOR was possible for couplings to HN7, HN9 and the proton at C8. Annealing the samples beyond 250K for several hours led to disappearance of Radical 1, and appearance of Radical 4. The evidence indicated that Radical 4 was the result of net hydrogen abstraction from N9 of the guanine base. The ENDOR results permitted full characterization of hyperfine couplings to HN7 and the two amino protons (the HN10s). From these results, and those from two other systems containing N7-protonated guanine bases, reaction mechanisms are proposed to account for formation of the products. PMID- 2903894 TI - Formation of cyclopyrimidines via the direct effects of gamma radiation of pyrimidine nucleosides. AB - Continuing our study of the direct effects of gamma radiation on DNA and its model compounds, we have isolated and characterized quantitatively an important lesion formed by irradiating pyrimidine 2'-deoxyribonucleosides in frozen aqueous solution. We report here the formation of 5',6-cyclo-5,6-dihydropyrimidine nucleosides via hydrogen abstraction at C5' of the osidic moiety with subsequent intramolecular attack at C6 of the base. We have so far managed to isolate six of the possible eight diastereomers of 5',6-cyclo-5,6-dihydrothymidine, and all four possible 5',6-cyclo-5,6-dihydro-2'-deoxyuridines formed by irradiation of 2' deoxycytidine. Also presented is a detailed discussion of the configurational analysis of each isomer based on 1H NMR data. PMID- 2903895 TI - Nuclear protein synthesis in thymocytes of X-irradiated rats. AB - The biosynthesis and phosphorylation of nuclear proteins of thymocytes were investigated in rats after 4.0 Gy whole-body X-irradiation during the period which precedes DNA degradation in lymphoid cells. Proteins were separated by two dimensional gel-electrophoresis, detected by Coomassie blue staining. Incorporation of [35S]methionine into proteins and phosphorylation of proteins with [32P]inorganic phosphate were determined by scanning densitometry of autofluorograms and autoradiograms, respectively. No change in the quantity of proteins was observed 1 h after irradiation. Decrease in specific activity of [35S]methionine-labelled proteins was seen in most protein fractions. Significant enhancement of phosphorylation of three proteins was established, characterized by molecular weight and pH: MW 20 kD, pH 6.8; MW 35 kD, pH 5.8 and MW 48 kD, pH 5.8. These results suggest that immediately after X-irradiation a short-term increase of chromatin-bound non-histone protein phosphorylation occurs. This finding, along with the previously described enhancement of RNA polymerase II in thymocytes (Zhivotovsky et al. 1982) suggests a temporary gene activation shortly after X-irradiation of the rat. PMID- 2903896 TI - Quantitation of intracellular Mac-1 (CD11b/CD18) pools in human neutrophils. AB - The adhesive glycoprotein Mac-1 (CD11b/CD18) of the CD11/CD18 complex contributes to multiple neutrophil inflammatory functions. Activation of neutrophils by chemotactic stimuli results in a rapid, protein synthesis-independent increase in surface Mac-1 derived from incompletely defined intracellular compartments. Therefore, we developed a novel quantitative lectin immunoblot technique to define intracellular pools of Mac-1 in subcellular neutrophil fractions resolved on discontinuous Percoll gradients. In cavitates of unstimulated neutrophils, 30% and 26% of total Mac-1 was identified in beta [1.10 gm/ml; vitamin B12 binding protein (vit B12 B.P.)-rich] or pre-gamma (1.07 gm/ml; vit B12 B.P.-poor) granular fractions, respectively, whereas 24% was associated with the plasma membrane-rich gamma (1.06 gm/ml) fractions. N-formyl-methionyl-leucyl phenylalanine (fMLP) stimulation (10(-8) M, 15 min, 37 degrees C) significantly diminished Mac-1 in pre-gamma (-18% of total, P less than 0.05) but not beta fractions (+6% of total). Under these conditions, the content of Mac-1 in gamma fractions increased 13% in association with four- to eightfold increase in surface Mac-1 expression (OKM-1 binding). These findings suggest that chemotactic stimuli increase plasma membrane and/or surface Mac-1 on human neutrophils by mobilizing a novel intracellular granule pool. PMID- 2903897 TI - Schizophrenia and its treatment. PMID- 2903898 TI - Neuropharmacological analysis of the control of LH secretion in gonadectomized male and female rats: altered hypothalamic responses to inhibitory neurotransmitters in long-term castrated rats. AB - The control of LHRH and LH by neurotransmitters and neuromodulators such as the endogenous opioid peptides is essentially the same in intact adult male and female rats: adrenergic and dopaminergic agonists stimulate LH release and opioid agonists inhibit it. Several weeks after gonadectomy, however, the contribution of the endogenous ligands of adrenergic, dopaminergic and opioidergic receptors to the control of LHRH is altered. A detailed pharmacological analysis in long term ovariectomized females confirmed previous reports that adrenergic and dopaminergic agonists still enhance secretion of LHRH and LH and opioid receptor agonists still suppress it. A similar investigation in long-term castrated males also confirmed previous reports that opioid agonists fail to block LH secretion. In addition, we have found that while adrenergic and dopaminergic agonists cause increases in serum concentrations of LH, adrenoreceptor and dopamine receptor antagonists do not inhibit LH release in long-term castrates. Furthermore, the opioid antagonist naloxone does not raise serum LH levels in either sex after long-term gonadectomy. These observations therefore imply reduced opioidergic, dopaminergic and adrenergic transmission, in relation to LHRH release, after long term castration. In addition, opioid receptor activity (assessed by responsiveness to an opioid receptor agonist) of female rats is maintained, whereas that of male rats is lost, after long-term gonadectomy. PMID- 2903899 TI - beta-Adrenergic blockade counteracts starvational ketosis, but aggravates post exercise ketosis in non-athletes. AB - Post-exercise ketosis is not abolished by glucose ingestion immediately after exercise but is counteracted by simultaneous beta-adrenergic blockade. To investigate the effect of beta-adrenergic blockade on post-exercise ketosis without the ingestion of glucose, we administered propranolol (1 mg/kg body mass) to 15 carbohydrate-starved people, of whom five had just walked 9 km in 2 h. There were 43 control subjects (no propranolol). The blood concentration of 3 hydroxybutyrate rose from 0.18 +/- 0.02 (S.E.M.) mmol/l at 07.00 h to 0.35 +/- 0.04 mmol/l at 09.00 h whether the subjects had exercised during those 2 h or not (d.f. = 57). The blood concentration of 3-hydroxybutyrate at 15.00 h in the groups not treated with propranolol was not affected by exercise (0.95 +/- 0.90 mmol/l; d.f. = 42). Propranolol significantly raised the concentration of 3 hydroxybutyrate at 15.00 h to 1.68 +/- 0.26 mmol/l when given after exercise (d.f. = 4), but lowered it to 0.46 +/- 0.07 mmol/l in the non-exercised group (d.f. = 9). This was not accompanied by significant differences in the blood concentrations of glucose, free fatty acid, insulin or glucagon. The difference in response to propranolol administration is probably determined by the alanine and lactate flux from muscle for hepatic oxaloacetate synthesis. PMID- 2903900 TI - Pseudomonas osteomyelitis secondary to puncture wound of the foot. PMID- 2903901 TI - Factors affecting oviposition site preference by Toxorhynchites splendens in the laboratory. AB - In a series of laboratory oviposition assays, gravid Toxorhynchites splendens exhibited a preference for cups containing Aedes aegypti larval rearing water, but not for cups containing liquid cultures of bacteria, live Ae. aegypti in distilled water, Ae. aegypti larval holding water with reduced bacterial contamination, or methyl propionate at 0.1, 0.2 and 0.3% in distilled water. Preoviposition flight behavior was elicited by dark-colored containers, but few eggs were deposited if they contained no water. An invisible source of humidity placed in cups enhanced oviposition, but a reflective surface placed in dry cups did not. It is concluded that this species is strongly influenced by humidity and visual stimuli in the acceptance of a site for oviposition. PMID- 2903902 TI - Hybridization of Aedes (protomacleaya) zoosophus with Ae. (Pro.) triseriatus group species: hybrid morphology. AB - Morphology of hybrids between Aedes (Protomacleaya) zoosophus and Ae. (Pro.) triseriatus group species is described. Adult females of hybrids key to Ae. zoosophus. Hybrids are differentiated from Ae. zoosophus by the dark longitudinal medial or submedial lines on the thorax and by the reduced width of the light tarsal and abdominal bands. The transverse band of light scales on the anterior scutum is complete in Ae. hendersoni/Ae. zoosophus hybrids and incomplete in Ae. triseriatus/Ae. zoosophus hybrids. Aedes brelandi/Ae. zoosophus hybrids are similar to Ae. hendersoni/Ae. zoosophus hybrids. However, due to the allopatric distributions of Ae. brelandi and Ae. zoosophus, such hybrids are not expected. PMID- 2903903 TI - Vector competence tests with Rift Valley fever virus and five South African species of mosquito. AB - Aedes juppi was readily infected by inoculation with virus but failed to transmit either horizontally or vertically. Seventy-five to 90% of the other 4 mosquito species became infected after ingesting 6.8-9.8 log10CPD50/ml of virus. These species all transmitted virus at the following rates on the post-infection days indicated: Aedes unidentatus (58%--day 11), Aedes dentatus (32%--day 11, 50%--day 18), Culex poicilipes (15%--day 15, 80%--day 30) and Aedes argenteopunctatus (14% on day 30). On the basis of these results and the relative prevalence of each species, it was concluded that Ae. unidentatus and Ae. dentatus are potential epizootic and possibly reservoir vectors and Cx. poicilipes a potential epizootic vector of Rift Valley fever virus in South Africa. PMID- 2903904 TI - Mosquito host range and field activity of Bacillus sphaericus isolate 2297 (serotype 25). AB - The 2297 isolate (serotype 25) of Bacillus sphaericus was bioassayed in the laboratory against 8 species of mosquitoes from 3 subfamilies. The most susceptible species were in the genus Culex and the least susceptible were the Aedes spp. and Toxorhynchites r. rutilus. Primary powders of the 2297 and 2362 (serotype 5a5b) isolates were evaluated in the field in natural and simulated habitats against Culex spp. The larvicidal activity of the two isolates was similar, with longer residual activity observed for both preparations in shaded shallow clear water. Larvicidal activity was curtailed in organically enriched and unshaded habitats. Isolate 2297 provided effective control for at least 1 week in an organically enriched habitat and for over 5 weeks in clear water in a shaded habitat when applied at the rate of 0.25 kg/ha. PMID- 2903905 TI - Mosquito productivity of crawfish ponds and irrigation canals in Louisiana ricelands. PMID- 2903906 TI - Attractant enhanced ovitraps for the surveillance of container breeding mosquitoes. PMID- 2903907 TI - Importation of Aedes albopictus and other exotic mosquito species into the United States in used tires from Asia. AB - Between May 18 and December 4, 1986, 79 seagoing containers and their contents of 22,051 used tires were inspected for adult mosquitoes as well as eggs and larvae. Of the total inspected, 5,507 tires (25%) contained significant amounts of water. No adults or eggs were found. Fifteen tires contained mosquito larvae that were identified as Ae. albopictus, Ae. togoi, Culex pipiens complex, Tripteroides bambusa and Uranotaenia bimaculata. The infestation rate for all species was 6.8 infested tires per 10,000 tires (wet and dry) inspected. Aedes albopictus larvae were most frequently collected, occurring at a rate of 20 infested wet tires per 10,000 inspected. PMID- 2903908 TI - Activities of four insect growth regulator formulations of fenoxycarb against Psorophora columbiae larvae. AB - Four formulations of fenoxycarb were evaluated at dosages of 0.022 and 0.011 kg ai/ha against Psorophora columbiae larvae in rice plots. Granular formulations, at both rates, provided moderate to excellent control of larvae introduced within 24 h posttreatment. A 1.0% fenoxycarb/200 ITU B.t.i. granule provided 86.2% reduction of emergence from larvae introduced at 120 h posttreatment. Aside from this formulation residual activity was lacking. The liquid formulation performed moderately well at the high rate against larvae introduced within 24 h; however, residual activity rapidly diminished. PMID- 2903909 TI - Sex difference in pupation of larval Culiseta melanura. PMID- 2903910 TI - Local superfusion modifies the inward rectifying potassium conductance of isolated retinal horizontal cells. AB - 1. Horizontal cells were enzymatically and mechanically dissociated from the white perch (Roccus americana) retina and voltage clamped using patch electrodes. Steady-state current-voltage (I-V) relationships of solitary horizontal cells were determined by changing the membrane potential in a rampwise fashion. 2. The I-V curve of cells bathed in normal Ringer solution exhibited a large conductance increase at negative membrane potentials. This conductance activated near the K+ equilibrium potential, had no clear reversal potential, was enhanced by raising the extracellular concentration of K+, and was suppressed by external Cs+. These properties identify the conductance as the inward (anomalous) rectifier. 3. Continuous superfusion of the cells' local environment with drug-free Ringer reduced the magnitude of the inward rectifier current and shifted its activation point to more negative potentials. This effect developed over approximately 30 s, lasted as long as superfusion continued and was reversible upon cessation of superfusion. 4. Pressure ejection of drug-free Ringer solution onto cells bathed in the identical solution also reduced the magnitude of the inward rectifier current, although the effects were more rapid and more transient than those exerted by superfusion. Pressure ejection had little effect when cells were simultaneously superfused with Ringer, suggesting a common mode of action on the inward rectifier. 5. In the absence of superfusion, pressure ejection of Ringer containing 200 microM L-glutamate had a biphasic effect on membrane conductance. At potentials above -60 mV, glutamate caused a conductance increase with a reversal potential near +10 mV. At potentials below -60 mV, glutamate caused a conductance decrease whose reversal potential could not reliably be determined. The latter effect was similar to the suppression of the inward rectifier by application of Ringer alone, suggesting that it may represent an artifact of pressure ejection rather than a direct effect of glutamate. 6. In support of this interpretation, we found that pressure ejection of glutamate in the presence of external Cs+ (which blocks the inward rectifier) or during local superfusion with Ringer (which prevents attenuation of the inward rectifier by pressure ejection) did not cause a conductance decrease at negative potentials. Under these conditions, glutamate caused primarily a conductance increase with a reversal potential near +10 mV.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2903911 TI - Selective expression of high-affinity nerve growth factor receptors on tyrosine hydroxylase-containing neuron-like cells in neural crest cultures. AB - A subpopulation of cultured neural crest cells undergoing differentiation have receptors for nerve growth factor (NGF) that exhibit a binding constant similar to that of the low-affinity NGF binding site (3.2 nM). Recent studies have shown that NGF receptors are not present on neuron-like cells immunoreactive for tyrosine hydroxylase (TH), serotonin, or vasoactive intestinal polypeptide. Since tissues innervated by sympathetic neurons in vivo produce NGF, we sought to determine whether NGF deficits in the tissue culture microenvironment may be one parameter preventing the expression of NGF receptors on TH-containing neuron-like cells. Neural crest cultures were therefore grown in complete tissue culture medium (15% fetal bovine serum and 5% chicken embryo extract), with or without exogenous NGF (50 ng/ml). Examination of light-microscopic radioautographs following incubation with 125I-NGF revealed that, if the cultures were supplemented with NGF for 7 d, approximately 33% of neuron-like cells exhibiting TH-like immunoreactivity possessed NGF receptors. There were no obvious morphological differences between TH-containing cells that did or did not have NGF receptors. Scatchard analysis of cultures grown under these conditions again demonstrated the sole presence of the low-affinity form of the NGF receptor (Kd, 3.4 nM). Embryonic catecholaminergic sympathetic neurons exhibit both high- and low-affinity forms of the NGF receptor, raising the possibility that the Scatchard analysis may not have been sensitive enough to detect the high-affinity form of the receptor on a relatively small population of cells. Therefore we used a morphological approach that took advantage of the different dissociation rates of the 2 receptor types.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903912 TI - L-glutamate increases internal free calcium levels in synaptoneurosomes from immature rat brain via quisqualate receptors. AB - Internal free calcium concentrations ([Ca2+]i) have been monitored in synaptoneurosomes from 8-d-old rat whole brain previously loaded with the calcium sensitive fluorescent probe Fura 2. Under basal conditions, [Ca2+]i was around 200 nM, this concentration increasing only slowly during storage of the synaptoneurosomes at room temperature (40% increase 2 hr after loading). Opening of sodium channels with veratridine- (10 microM) or KCl- (30 mM) induced depolarization caused rapid increases in synaptoneurosomal [Ca2+]i. [Ca2+]i was also markedly increased by addition of the Ca2+ ionophore A23187 (10-100 nM). The effect of veratridine, but not of KCl was prevented by previous addition of TTX (1 microM). KCl-induced [Ca2+]i increase was dependent on external Ca2+ and was partially blocked by the dihydropyridine derivative PN 200-110 (IC50 0.15 microM, maximal inhibition 55% at 3 microM). L-Glutamate elicited a concentration dependent fast increase in synaptoneurosomal [Ca2+]i in the 8-d-old (but not in the adult) rat brain (EC50 = 2 microM). The effect of glutamate was stereospecific, the EC50 of the D-isomer being 47 times higher than that of L isomer. The magnitude of the L-glutamate response differed in several brain regions, being highest in the cerebral cortex and lowest in the cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903913 TI - Regulation of hypothalamic magnocellular neuropeptides and their mRNAs in the Brattleboro rat: coordinate responses to further osmotic challenge. AB - A paradigm was developed for the chronic osmotic stimulation of homozygous diabetes insipidus rats of the Brattleboro strain, a strain that fails to synthesize vasopressin. This study examines the adaptation of 2 sets of coexisting peptide hormone magnocellular neurons in the hypothalamoneurohypophyseal system (HNS) of Long Evans (LE), Brattleboro heterozygote (HZ), and Brattleboro homozygote (DI) rats: (1) the arginine8 vasopressin (AVP)/dynorphin (DYN) neurons, and (2) the oxytocin (OT)/cholecystokinin (CCK8) neurons of the paraventricular and supraoptic nuclei, which project to the posterior pituitary. The regimen of chronic intermittent salt-loading (CISL) involved the replacement of 2% saline for normal drinking water for 18 hr/d. This protocol effectively increased plasma levels of AVP and OT in LE and HZ rats, oxytocin in DI rats, and maintained the posterior pituitary in a state depleted of AVP, OT, CCK, and peptides derived from pro-dynorphin: DYN A 1-17, DYN A 1-8, and DYN B 1-13. The ratio of pituitary DYN A 1-17 to DYN A 1-8 content in DI rats or in LE, HZ, and DI rats following 6 d of CISL suggests a preferential release of DYN A 1-17 during periods of chronic secretory activity. In response to chronic secretory activity, mRNAs for AVP, OT, DYN, and CCK increased 1.5-2-fold in all 3 AVP rat strains, with mRNAs for coexisting peptide hormones displaying parallel increases. Mutant AVP mRNA in the DI rat was expressed at very low levels and DYN mRNA in very high levels, with each of these mRNAs continuing to be regulated by CISL in a normal manner. These results suggest a regulatory relationship between AVP and OT neurons, in which vasopressin neurons are feedback-regulated by AVP, most likely via plasma osmolarity, and that oxytocin neurons are modulated by peptides derived from pro dynorphin. PMID- 2903914 TI - Glycine potentiates strychnine-induced convulsions: role of NMDA receptors. AB - Strychnine poisoning leads to seizures that have traditionally been attributed to competitive antagonism of glycine receptors in the spinal cord. Although glycine is thought to act as an inhibitory neurotransmitter, a strychnine-insensitive glycine (Gly2) receptor has been recently described in cultured mouse neurons that is thought to be allosterically linked to the excitatory amino acid NMDA receptor. The present study demonstrates that intrathecally administered glycine, in contrast to other putative inhibitory transmitters, potentiates rather than inhibits strychnine-induced convulsions in mice. The seizure-potentiating effects of glycine are blocked by aminophosphonovaleric acid, an NMDA antagonist. In addition, in animals pretreated with a subconvulsive dose of strychnine to block strychnine-sensitive glycine receptors (Gly1), glycine enhances, rather than inhibits, NMDA-induced convulsions. Together, these results indicate that the seizure-potentiating effects of glycine involve activation of NMDA receptors. This study provides the first evidence that glycine is capable of modulating the activity of NMDA receptors in the spinal cords of adult animals. In light of the elevated concentrations of glycine found in epileptogenic brain foci, these data also suggest that glycine may be a positive modulator in the production of epileptic seizures. PMID- 2903915 TI - Spontaneous release of acetylcholine affects the physiological nicotinic responses of rat retinal ganglion cells in culture. AB - Nictonic cholinergic responses have been previously documented in mammalian retinal ganglion cells. In the present study, dissociated retinal cells were densely plated and grown in a specific batch of rat serum. When held at negative potentials during whole-cell recording with a patch electrode, the retinal ganglion cells located close to presumptive cholinergic amacrine cells in these cultures were found to respond to acetylcholine (ACh; 20-200 microM) with an apparent outward current in the presence of physiological salines on both sides of the membrane. Other nicotinic agonists (nicotine, carbachol) produced the same effect. Conductance measurements revealed that this apparent outward current was actually a decrease in a tonic inward current. Nicotinic antagonists such as d turbocurarine (10 microM) and dihydro-beta-erythroidine (20 microM), when applied in dishes that had never been exposed to exogenous ACh, produced a similar decrease in a tonic inward current. The reversal potential of the tonic current suppressed by ACh was similar to the nicotinic current previously studied in these central neurons. Furthermore, purified acetylcholinesterase was capable of modulating the tonic inward current of the retinal ganglion cells. Lowering an excised patch of muscle into dense areas of the retinal cultures activated nicotinic channels in the muscle membrane, indicating the presence of endogenous ACh in the culture fluid. Divalent cations such as Co2+ blocked the tonic inward current of retinal ganglion cells in these cultures. Finally, direct biochemical measurements indicated that low levels of endogenous ACh (on the order of 0.5 microM near putative cholinergic amacrine cells) were present in the retinal cultures. Taken together, these results show that ACh was being spontaneously released into these cultures, resembling at least to some degree the tonic leakage of ACh found in the intact retina. This concentration of ACh was capable of tonically depolarizing the membrane potential of retinal ganglion cells exposed to this dosage. This culture system allows the study of trophic effects of ACh on a central mammalian neuron in a precisely controlled extracellular environment. PMID- 2903916 TI - Different times of origin of choline acetyltransferase- and somatostatin immunoreactive neurons in the rat striatum. AB - Two populations of aspiny interneurons have been identified in the mammalian striatum, one cholinergic and the other using the neuropeptide somatostatin as a neurotransmitter. The times at which these 2 cell populations undergo their final mitosis were studied by injecting tritiated thymidine into timed pregnant rats and then processing the brains of the progeny as young adults for immunohistochemistry with monoclonal antibodies to choline acetyltransferase and somatostatin followed by autoradiography. Choline acetyltransferase immunoreactive neurons became postmitotic in a caudal-to-rostral gradient; the occurrence of final mitosis was maximal on embryonic day (E) 12 at the most caudal level and on E15 at the most rostral. A more subtle lateral-to-medial gradient was also observed in the precommissural striatum. In contrast, no obvious gradients were seen with somatostatin-immunoreactive neurons; regardless of their location within the striatum, these neurons underwent their final mitosis on days E15-16, towards the end of cholinergic neurogenesis. These results indicate that although both cholinergic and somatostatin-containing cells represent interneuronal populations in the striatum, they display distinctly different spatiotemporal patterns of neurogenesis. PMID- 2903917 TI - Calcitonin gene-related peptide prevents disuse-induced sprouting of rat motor nerve terminals. AB - Calcitonin gene-related peptide (CGRP) coexists with acetylcholine (ACh) in motor nerve terminals. Externally applied CGRP has been shown to increase the synthesis of ACh receptors in cultured myotubes by a mechanism independent of muscle activity. Thus, CGRP is suggested to be a neurotrophic factor that may regulate the expression of several long-term events occurring at the neuromuscular junction. We have examined the effect of CGRP on the sprouting of motor nerve terminals induced by chronic block of nerve-muscle activity in adult rats. Daily treatment with CGRP suppressed the disuse-induced terminal sprouting in a dose dependent manner, whereas the morphology of motor nerve terminals in active muscles was unaffected by CGRP. CGRP may be a possible candidate for an antisprouting agent which has been postulated to exist in nerve terminals. The disuse-induced outgrowth of terminal sprouts was accompanied by an increase in the mean quantum content of end-plate potentials, as well as in the frequency of spontaneous miniature end-plate potentials. This increased transmitter release was still maintained at the junctions in which disuse-induced terminal sprouting had been suppressed by CGRP. It is suggested that the formation of terminal sprouts per se is not responsible for the plastic change of transmitter release induced by prolonged disuse of the neuromuscular junction. PMID- 2903918 TI - Glutamine and asparagine synthesis in the nematodes Heligmosomoides polygyrus and Panagrellus redivivus. AB - Low levels of glutamine synthetase were demonstrated in Panagrellus redivivus and Heligmosomoides polygyrus. Asparagine synthetase was detected in P. redivivus but activity was too low to be detected in H. polygyrus. PMID- 2903920 TI - Psychosocial changes in persistently psychotic schizophrenic patients after an 80% reduction of neuroleptic medication [corrected]. PMID- 2903919 TI - Purinergic reception by culicine mosquitoes. AB - 1. Adult female Culex pipiens and Culiseta inornata have purinergic receptors that respond to extracellular ADP and related compounds. Stimulation of these receptors caused ingestion of artificial diets. Addition of bicarbonate to the saline solvent enhanced the phagostimulatory effect. Saline-bicarbonate was as effective a solvent as blood plasma for Cx. pipiens, and was used in the dose effect determinations. Ranking of the potencies was: ADP greater than AMP-PNP greater than ATP = AMP greater than AMP-PCP much greater than 2'dAMP greater than 2'dADP greater than 2'dATP. At 1 mM concentration, ITP, GTP, CTP, UTP, c-AMP, 2'AMP, 3'AMP, DPG, or GSH + glucose caused fewer than 50% of the insects to gorge, as did 2'3'dd-ATP, A tetra P, and AMP-CPP at 100 microM. 2. The potency ranking for Cu. inornata was: ADP greater than AMP-PNP greater than ATP greater than AMP-PCP much greater than AMP much greater than AMP-S. The concentrations required to produce the ED50 response (inducing 50% of the test insects to gorge) were much higher than those required for Cx. pipiens; however, saline, not saline bicarbonate, was used as the solvent. With the exception of the very low potency of AMP for Cu. inornata, the ADP potency index values for the other chemicals tested on both species are similar.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2903921 TI - It's on the tip of the tongue tardive dyskinesia. PMID- 2903922 TI - History of enteric coated sulfasalazine in rheumatoid arthritis. AB - Sulfasalazine was synthesized almost 50 years ago specifically to treat rheumatoid arthritis. At that time bacterial infection was believed to be an important factor in pathogenesis. The linkage of sulfapyridine and salicylate with an azobond was viewed as a method of combining antibacterial and antiinflammatory actions while minimizing gastric irritation. Early therapeutic results were encouraging, but the drug was discarded as an antirheumatic agent for 30 years, until its serendipitous rediscovery. Subsequent controlled trials have confirmed its efficacy, which may be related to sulfasalazine itself or to the sulfapyridine moiety. PMID- 2903923 TI - The safety of sulfasalazine: the gastroenterologists' experience. AB - Although the incidence of side effects associated with sulfasalazine is in the range of 20%, most of the common side effects, including gastrointestinal reactions and headache, can be managed by dosage adjustment. In patients who experience allergic reactions of rash, fever, and arthralgia, therapy can usually be resumed after a program of desensitization. The risks associated with chronic low-grade hemolysis can be avoided by careful monitoring and, when necessary, folic acid supplementation. Certain idiosyncratic reactions to sulfasalazine do, however, represent absolute contraindications to further use of the drug. Sulfasalazine may cause reversible male infertility, but it is entirely safe for use during pregnancy and lactation. Overall, sulfasalazine has a long and impressive safety record, provided the drug is used with an awareness and appreciation of its potential pitfalls. PMID- 2903924 TI - Adverse reactions to sulfasalazine: the British experience. AB - Sulfasalazine has been used for a decade in the United Kingdom for treating rheumatoid arthritis. There is now considerable experience with its adverse reaction profile and the incidence of serious events. In the initial weeks of treatment minor side effects are common, especially upper gastrointestinal problems and nausea. Therapy is thus usually introduced slowly and enteric coated tablets are preferred. In 20-30% of patients treatment is discontinued due to an adverse reaction. Most of such reactions occur within 3 months of starting therapy, are trivial, and are self-limiting after withdrawal of the drug. Potentially more serious adverse reactions include leukopenia, rash, abnormal liver function tests, and dyspnea. These reactions also reverse after treatment is stopped. Side effects leading to drug withdrawal after 1 year of therapy are unusual. PMID- 2903925 TI - Treatment of the seronegative spondyloarthropathies with sulfasalazine. AB - Three patients with reactive arthritis and 2 with ankylosing spondylitis resistant to therapy with nonsteroidal antiinflammatory drugs were treated with enteric coated sulfasalazine in an open trial. Significant toxicity was not observed; 1 patient discontinued sulfasalazine because of gastrointestinal symptoms. As a group, statistically significant improvement was observed in 50 foot walk time, morning stiffness, and hemoglobin concentration. One patient went into complete clinical remission, 2 improved, 1 showed no change, and 1 worsened. Asymptomatic colonic inflammation was found in each of 4 patients examined before beginning therapy. Changes in bowel pathology did not parallel changes in joint symptoms. Sulfasalazine may be a safe and useful therapeutic modality in patients with chronic reactive arthritis or ankylosing spondylitis. PMID- 2903926 TI - What is a disease modifying antirheumatic drug? AB - The disease modifying antirheumatic drugs (DMARD) used to treat rheumatoid arthritis (RA) are distinct from the nonsteroidal antiinflammatory drugs (NSAID) in their slow onset of antiinflammatory action, their lack of analgesic properties, their more frequent and severe toxicity, and in the opinion of some experts, their ability to produce more frequent remissions and slow the progression of erosions. New DMARD prospects include less toxic immune modulating agents, as well as NSAID/DMARD hybrids. Although currently available DMARD are considered primarily treatment for RA, sulfasalazine may be such a drug for B27 arthropathies as well. Future studies may lead to the development of agents that are specific modifiers of other rheumatic diseases, including lupus and scleroderma. PMID- 2903927 TI - Comparison of responses to and adverse effects of graded doses of sulfasalazine in the treatment of rheumatoid arthritis. AB - Sulfasalazine (0, 0.5, 1, or 2 g daily in divided doses) was given to patients with definite or classical rheumatoid arthritis (RA) insufficiently controlled by a nonsteroidal antiinflammatory drug. Grip strength, Westergren sedimentation rate, and physician and patient global assessment improved in those patients given 2 g/day. Inadequate response was the primary reason for withdrawal in the groups given placebo or 0.5 g/day, while adverse reactions (mainly gastrointestinal upset or rash) accounted for most withdrawals from the groups that received 1 or 2 g/day. Although its use is limited by adverse reactions, sulfasalazine is effective in the treatment of patients with RA. PMID- 2903928 TI - Comparisons of sulfasalazine to gold and placebo in the treatment of rheumatoid arthritis. AB - Studies comparing sulfasalazine to gold or placebo are few in number. Two controlled trials have been conducted comparing sulfasalazine and placebo, and 2 uncontrolled trials have compared sulfasalazine and gold sodium thiomalate. A controlled trial conducted by the Cooperative Systematic Studies of Rheumatic Diseases compared enteric coated sulfasalazine, gold, and placebo. These studies suggest that sulfasalazine is superior to placebo but is associated with significant side effects, particularly gastrointestinal. These studies also suggest that sulfasalazine is similar in efficacy to gold, but with lesser and milder toxicity. Additional comparison studies are indicated. PMID- 2903929 TI - Antihypertensive activity in a series of 1-piperazino-3-phenylindans with potent 5-HT2-antagonistic activity. AB - A series of trans-1-piperazino-3-phenylindans were synthesized with the goal of replacing their established neuroleptic profile with that of peripheral 5 hydroxytryptamine (5-HT2) antagonism. Compounds with an unsubstituted or fluoro substituted 6-position in the indan ring, and which had a five- or six-membered heterocyclic ring attached by an ethylene chain to the piperazine ring, satisfied this objective. Some of the compounds had potent antihypertensive activity in conscious, spontaneously hypertensive rats (SHR). In pithed rats they antagonized the pressor effect induced by 5-HT in doses 100-1000 times lower than doses needed to antagonize the pressor effect of phenylephrine. The effect was stereoselective and associated with enantiomers with 1R,3S absolute configuration. 1S,3R enantiomers inhibited the uptake of dopamine and norepinephrine in vitro. The compound with the best antihypertensive activity was (+)-(1R,3S)-1-[2-[4-[3-(4-fluorophenyl)-1-indanyl]-1- piperazinyl]ethyl]-2 imidazolidinone (Lu 21-098, irindalone). Its pharmacological profile resembled that of the standard compound ketanserin. There was a close structural correspondence between ketanserin and irindalone in a conformation that we recently identified as a D-2 receptor-relevant configuration of its neuroleptic "parent" tefludazine. This suggests that the dopaminergic (D-2) and the serotonergic (5-HT2) pharmacophores are structurally closely related. PMID- 2903930 TI - Synthesis, absolute configuration, and molecular modeling study of etoxadrol, a potent phencyclidine-like agonist. AB - Etoxadrol (2a), one of the eight possible optical isomers of 2-ethyl-2-phenyl-4 (2-piperidyl)-1,3-dioxolane, was synthesized from (S,S)-1-(2-piperidyl)-1,2 ethanediol, which was obtained from cleavage of dexoxadrol (1a, (S,S)-2,2 diphenyl-4-(2-piperidyl)-1,3-dioxolane). The absolute configuration of etoxadrol hydrochloride, a phencyclidine-like compound biologically, was determined to be 2S, 4S, and 6S at its three chiral centers by single-crystal X-ray analysis. Epietoxadrol (2b), epimeric with etoxadrol at the C-2 center, was also obtained from the synthesis. This much less potent enantiomer has the 2R,4S,6S configuration. The affinity of etoxadrol to the phencyclidine binding site was found to be comparable to that of phencyclidine itself and was 35 times more potent than its epimer, epietoxadrol. Three diastereomeric mixtures were prepared that had low affinity for the phencyclidine site. In studies of the discriminative stimulus properties of these compounds, it was found that only etoxadrol substituted for the phencyclidine stimulus. With use of computer assisted molecular modeling techniques, a hypothetical phencyclidine binding site model has been developed that, unlike our former hypothesis based on Dreiding models, correctly predicts the higher affinity of etoxadrol and the lesser affinity of epietoxadrol for the phencyclidine site. PMID- 2903931 TI - Synthesis and pharmacological properties of "soft drug" derivatives related to perhexiline. AB - In the hope of reducing the toxicity of perhexiline, a series of 27 cyclohexylaralkylamines II based on the "soft drug" concept and incorporating an amide function were synthesized. In a preliminary screening, compounds were evaluated for their alpha-adrenolytic activities. Several derivatives, especially N-(cyclohexylphenylmethyl)-2-(cyclohexyl-methylamino)acetamide (3), N (cyclohexylphenylmethyl)-2-(homoveratrylmethylamino)acetam ide (7), and N-[2 (cyclohexylamino)ethyl]-alpha-cyclohexylbenzeneacetamide (23) had the same activity range as perhexiline in vitro in rat aorta strips. The in vitro metabolism of these three molecules was then investigated and compared to that of perhexiline. The effect upon the alpha-adrenolytic activity of introducing various N-aralkylamine groups on II was examined. Structure/activity relationships are discussed. PMID- 2903933 TI - Host-feeding patterns of mosquitoes (Diptera: Culicidae) in a rural village near Cairo, Egypt. PMID- 2903932 TI - Structure-activity relationships in 1,4-benzodioxan-related compounds. Investigation on the role of the dehydrodioxane ring on alpha 1-adrenoreceptor blocking activity. AB - Several analogues of 2-[[[2-(2,6-dimethoxyphenoxy)ethyl]amino]methyl]-1,4 benzodioxa n (WB 4101, 1) were prepared and evaluated for their blocking activity on alpha 1- and alpha 2-adrenoreceptors in the isolated rat vas deferens. The results were compared with those obtained for 1 and benoxathian (2). It was shown that the two oxygens at positions 1 and 4 may have a different role in receptor binding. It seems that the oxygen at position 4 as such does not contribute to the binding while it is important in stabilizing an optimal conformation for drug receptor interaction mechanism. On the other hand, the oxygen at position 1 might interact with a receptor polar pocket of reduced size by way of a donor-acceptor dipolar interaction. Furthermore, it was shown that replacement of the dehydrodioxane ring of 1 by a phenyl or a pyrrole nucleus causes a significant decrease in activity. PMID- 2903934 TI - Pathogenicity of capsulate and non-capsulate members of Bacteroides fragilis and B. melaninogenicus groups in mixed infection with Escherichia coli and Streptococcus pyogenes. AB - The relationships between capsulate and non-capsulate Bacteroides fragilis strains and Escherichia coli, and between capsulate and non-capsulate strains of the B. melaninogenicus group and Streptococcus pyogenes, were studied in a subcutaneous abscess model in mice. Selective antimicrobial agents directed against either aerobic or anaerobic bacteria were used alone or in combination to explore the effect of eradication of one component of the mixed infection. Single agent therapy effective against both aerobic and anaerobic flora was also employed. Single therapy of mixed infection directed at the elimination of only one organism (S. pyogenes, E. coli or Bacteroides sp.) caused significant reductions in the numbers of sensitive organisms and also smaller yet significant decreases in the numbers of insensitive organisms. However, the abscesses were not eliminated after such therapy. Combination therapy or use of a single agent (cefoxitin) directed against the aerobic and anaerobic components of the infection was more effective. Non-capsulate Bacteroides spp. became capsulate after passage in mice mixed with either S. pyogenes or E. coli. Therapy directed at the elimination of S. pyogenes and E. coli did not prevent the emergence of capsulate Bacteroides spp. These data demonstrate the synergy between all members of the B. fragilis group and E. coli and between the B. melaninogenicus group and S. pyogenes, and reiterate the need to direct antimicrobial therapy at the eradication of the aerobic and anaerobic components of mixed infections. PMID- 2903937 TI - Catecholamine metabolism in pheochromocytoma and normal adrenal medullae. AB - The tissue contents of catecholamine, its precursor and its major metabolites were determined in 8 human pheochromocytomas and 26 normal adrenal glands. Pheochromocytomas contained significantly larger amounts of norepinephrine, dopamine, dihydroxyphenylalanine, tyrosine hydroxylase activity, metanephrine, normetanephrine and vanillylmandelic acid than did normal adrenal medullae. The content ratio of epinephrine/norepinephrine in normal adrenal medullae was significantly higher than that in pheochromocytomas but there were considerable individual variations in the metanephrine/normetanephrine and vanillylmandelic acid/3-methoxy-4-hydroxyphenylethylglycol ratios in pheochromocytomas. In normal adrenal medullae the tissue content of tyrosine hydroxylase activity correlated inversely with the tissue contents of epinephrine (r equals -0.78, p less than 0.001), norepinephrine (r equals -0.78, p less than 0.001) and total catecholamines (r equals -0.87, p less than 0.001), respectively but no significant relation was found between both parameters in pheochromocytomas. These results indicate the possible presence of a negative feedback mechanism of catecholamine via tyrosine hydroxylase in normal adrenal medullae but none in pheochromocytomas. In addition, the increased degradation catecholamine pathway in pheochromocytomas appears to be unstable compared to that in normal adrenal medullae. PMID- 2903936 TI - Benzodiazepine-receptor antagonist, a clinical double blind study. AB - In a double blind study including 18 patients in whom a benzodiazepine intoxication was suspected, the first specific benzodiazepine antagonist was compared to placebo. There was a highly significant effect on consciousness, all patients given antagonist awaked, usually within minutes. No adverse effects were observed. In 2 patients the clinical condition deteriorated 1 to 2 hrs after the antagonist was given. This might endanger intoxicated patients withdrawing from medical attention. PMID- 2903938 TI - Re: Laparoscopy in the management of the nonpalpable testis. PMID- 2903939 TI - A new test to predict reversibility of hydronephrotic atrophy after stable partial unilateral ureteral obstruction. AB - In previous studies we showed that hydronephrotic atrophy develops only in the first weeks after stable partial ureteral obstruction, and does not progress thereafter. Relief of obstruction only in the "destructive phase" and not in the later "steady-state phase" seems to improve or prevent hydronephrotic atrophy. Since the duration of partial ureteral obstruction is often not known, we studied urinary enzymes of rat kidneys after stable partial unilateral ureteral obstruction to identify the destructive phase. We chose as an example of the tubular lysosomal enzyme N-acetyl glucosaminidase (NAG) and as an example of the brush border enzyme gamma-glutamyl-transferase (Gamma-GT). NAG concentration but not so much Gamma-GT concentration was higher in the urine of the obstructed kidneys than in the urine of the contralateral control kidney, in the first two weeks after operation, and then returned to normal. These observations lead to the conclusion that the "destructive phase" after ureteral obstruction can be identified by the appearance of high urinary tubular lysosomal enzyme content. The clinical implication is that the timing of relief of asymptomatic stable partial ureteral obstruction of unknown duration can be based on the concentrations of urinary lysosomal enzymes. PMID- 2903940 TI - Clostridium absonum from gas gangrene. AB - A Clostridium perfringens-like strain was isolated from a case of gas gangrene. The morphological properties and the lecithinase reaction of the isolate were very similar to those of C. perfringens; however, the lecithinase reaction was only slightly suppressed by C. perfringens alpha-antitoxin serum and the organism was identified as Clostridium absonum from its biochemical properties. PMID- 2903941 TI - Separation of sulfated, fucose-containing polysaccharides from the brown seaweed Sargassum kjellmanianum and their heterogeneity and antitumor activity. PMID- 2903942 TI - [Disseminated livedo angiitis]. PMID- 2903943 TI - [Senile, hereditary and local amyloidosis]. PMID- 2903944 TI - [The main reasons for diagnostic errors at the therapeutic clinic]. PMID- 2903935 TI - Calcium channels: molecular pharmacology, structure and regulation. PMID- 2903945 TI - Acute effects of a khat extract on the rat electroencephalogram. AB - Rats chronically implanted with cortical screw electrodes were treated with three different oral doses of a Khat extract and the EEG recorded for 5 h. Several abnormalities in EEG patterns were observed, particularly after the administration of the largest dose (400 mg/kg). Spectral analysis of EEG showed a significant shift of frequencies towards faster, lower voltage activity following administration of the two smaller doses (50 and 100 mg/kg), reflecting a stimulant effect of the extract. The highest degree of cortical activation was observed following administration of the smallest dose. With the largest dose, an initial activation was followed by a state of EEG depression characterized by a high percentage of slow, high voltage waves. It is concluded that Khat extract in small doses has a stimulant effect on the rat brain, but with larger doses induces a state of depression. PMID- 2903946 TI - Takayasu's arteritis with bilateral pulmonary artery stenosis. PMID- 2903947 TI - Establishment of a hemopoietic stimulating factor producing murine leukemia cell lines: pathogenesis of granulocytosis in L8313 bearing mice. AB - Thy 1.2+ cells of L8313 leukemia bearing mice were previously shown to produce granulocyte macrophage colony stimulating activity (GM-CSA) and interleukin-3 (IL 3). Cell lines with the Thy 1.2+ phenotype were established from spleen cells of the leukemic mice, and were designated STIL-3 C5 and STIL-3 D10. They produced and released GM-CSA and IL-3 activities in culture supernatant. C5 cells were phenotypically Thy 1.2+ and Lyt 2.1+ with rearrangement of the T-cell receptor beta chain gene also being identified. D10 was Thy 1.2+ and L3T4+ with T-cell receptor beta chain gene rearrangement not detectable. Since the same sized rearranged bands were observed between C5 and L8313 leukemic mouse spleen cells, it is indicated that C5 cells are derived from the leukemic cells. Inoculation of these cells into mice induced granulocytosis. These results indicated that L8313, which was thought to be a "granulocytic leukemia", is actually a T-cell leukemia, whose granulocytosis is a leukemoid reaction induced by normal hemopoietic cells responding to the hemopoietic stimulating factors, GM-CSA and IL-3, produced by the leukemic T cells. Thus, L8313 should be known as a T-cell leukemia associated with granulocytosis. PMID- 2903948 TI - Transglutaminase in cell proliferation and transformation. AB - Transglutaminase (TGase) activity was reduced in intact mitogen-stimulated human peripheral blood lymphocytes (PBL) when compared to intact resting PBL. Moreover, a treatment of the same quiescent immunocompetent cells with purified liver TGase and Ca2+ completely suppressed the mitogen-induced blast transformation. A decrease in TGase activity in neoplastically transformed seminal vesicle epithelial cells with respect to their normal parent counterpart was also observed. Our data support the notion of a possible implication of TGase in cell proliferation and transformation. PMID- 2903949 TI - [Therapeutic use of somatostatin in pathology of the digestive system]. PMID- 2903950 TI - Atypical antipsychotics--recent findings and new perspectives. PMID- 2903951 TI - Effects of drug treatment on human resistance arteriole morphology in essential hypertension: direct evidence for structural remodelling of resistance vessels. AB - To examine whether effective drug treatment would reverse the morphological changes in resistance arterioles which characterise untreated essential hypertension, the vessels' media thickness and contractility were measured before and after long-term treatment. Nine patients underwent skin biopsy before and after a mean 13 months of antihypertensive treatment (range 4-24 months). Subcutaneous resistance arterioles were dissected and mounted in a myograph. Treatment did not affect the shift in sensitivity to noradrenaline in the presence of cocaine, sensitivity to exogenously administered calcium, and the rate of relaxation after withdrawal of vasoconstrictor stimuli. The media/lumen ratio fell significantly (p = 0.011) owing to a significant regression in media thickness (p = 0.0195), but this was not complete. Thus, effective antihypertensive treatment can reverse some of the structural change observed in the untreated state, although it apparently does not affect calcium sensitivity or relaxation rate; these features are thought to be consequences of the disease after it has become established. PMID- 2903952 TI - Correlation between cranial computed tomographic scans at diagnosis in children with acute lymphoblastic leukaemia and central nervous system relapse. AB - 145 children with acute lymphoblastic leukaemia (ALL) were evaluated over a period of 3 years in a multicentre study in which serial cranial computed tomographic (CT) scans of the brain were done. All patients were symptom-free. CT scans were graded as normal, borderline (slight or moderate cerebral atrophy), or pathological (severe cerebral atrophy). 62% (90/145) of children had CT scan abnormalities at diagnosis. After a median follow-up of 24 months (range 6-36) 12 of 108 evaluable patients had central nervous system (CNS) relapses (6 isolated relapses and 6 combined with relapse at another site). All patients with CNS relapse had an abnormal CT scan at diagnosis (8 pathological and 4 borderline). No relapses were observed among the 42 patients with a normal cranial CT scan at diagnosis. A significantly higher proportion of severe cerebral atrophy, both following CNS prophylaxis and after the discontinuation of treatment, was found among patients with a borderline CT scan at diagnosis than among patients with a normal CT scan at diagnosis. Thus an abnormal cranial CT scan at diagnosis in children with ALL seems to have prognostic significance. PMID- 2903953 TI - Clinical and virological effects of high-dose recombinant interferon-alpha in disseminated AIDS-related Kaposi's sarcoma. AB - The effectiveness and antiretroviral activities of interferon-alpha in AIDS related Kaposi's sarcoma was assessed in a non-randomised, phase-II clinical trial. 28 patients were treated with high-dose (27-36 MU) human recombinant interferon-alpha 2a subcutaneously every day for 8 weeks. In patients with stable disease or showing a response, treatment was continued three times weekly until a complete response was achieved or there was progression. 12 of the 26 evaluable patients achieved a major response; 5 of these showed histologically confirmed complete responses. There was a significant increase in OKT4-positive cells in the responders and a significant decrease in HIV antigen (HIV-Ag) in the 7 responders with initially detectable HIV-Ag. Interferon-alpha is thus an effective treatment. The increase in OKT4-positive cells and the decrease in HIV Ag seem to be significantly related to patients with tumour responses. PMID- 2903954 TI - Anti-retroviral effects of interferon-alpha in AIDS-associated Kaposi's sarcoma. AB - 21 patients with AIDS and Kaposi's sarcoma were enrolled in an open therapeutic trial to determine the in vivo anti-retroviral activity of recombinant interferon alpha (IFN-alpha). 8 (38%) showed a complete or partial anti-tumour response. The mean pretreatment CD4 count for the responders was 399 cells/microliter vs 154 cells/microliter for the non-responders. All 5 of the patients with more than 400 CD4 cells/microliter pretreatment showed a significant reduction in tumour, whereas none of the 7 patients with under 150 CD4 cells/microliter had any response. 5 of the 6 complete or partial responders with greater than 50 pg/ml of human immunodeficiency virus (HIV) p24 before IFN therapy showed a 75% or greater reduction by 12 weeks of therapy, with 3 patients having persistently negative HIV cultures. The anti-viral effects were also most pronounced in the patients with the highest CD4 counts. These data demonstrate the potential benefits, both anti-tumour and anti-retroviral, of treatment with IFN-alpha in the early stages of HIV infection and Kaposi's sarcoma. PMID- 2903955 TI - Prevention of gallstone recurrence by non-steroidal anti-inflammatory drugs. AB - In laboratory animals, non-steroidal anti-inflammatory drugs (NSAIDs) are reported to inhibit diet-induced gallstone formation. To see if these drugs had a similar effect in man, 82 patients who had taken part in a comparison of ursodeoxycholic acid, placebo, and diet for prevention of gallstone recurrence were sent questionnaires about their use of NSAIDs during the period of the trial. 75 replied. After a mean follow-up of 33 (SEM 4) months none of the 12 regular users of NSAIDs had had gallstone recurrences, compared with 20 of the 63 who never or rarely used these drugs (p less than 0.02). PMID- 2903956 TI - Defenestration of hepatic sinusoids as a cause of hyperlipoproteinaemia in alcoholics. AB - The hepatic sinusoidal endothelium separates sinusoidal blood from hepatocytes; changes in the porosity of this endothelium may affect the passage of chylomicrons into hepatocytes and influence lipid metabolism. Chronic exposure to ethanol reduces the porosity of the endothelium; this mechanism may underlie the hyperlipoproteinaemia observed in some people who drink heavily. PMID- 2903958 TI - Growing up with coeliac disease. PMID- 2903957 TI - Sodium valproate. PMID- 2903959 TI - Nephrogenic ascites. PMID- 2903960 TI - Myocarditis, histology, and immunosuppression. PMID- 2903961 TI - Cyclosporin hypertension. PMID- 2903962 TI - Epidemiology of retinopathy of prematurity. AB - The incidence and severity of retinopathy of prematurity (ROP) were studied prospectively in a geographically defined area of the East Midlands. Over 23 months, 505 infants weighing 1700 g or less at birth to mothers resident in this area were studied. Acute ROP developed in 248 (49.1%) and there was a significant association between short gestation and low birthweight and greater severity. Most acute ROP underwent complete resolution; only stage 3/4 disease did not and cicatricial sequelae subsequently developed in 5 infants, 23.8% of this group. No infant was blind because of ROP. Black infants had shorter gestations yet were less likely to have any stage of ROP. Although Asians were not smaller than their caucasian counterparts, severe (stage 3/4) ROP was more likely (14.1% vs 2.7% for caucasians); this difference was largely due to their better survival. Since 505 of the available 547 infants in this geographically defined area were examined, it was possible to calculate the incidence of acute and cicatricial ROP on a community population basis. There are dangers in attempting to deduce the incidence of acute ROP from infrequent eye examinations, and in comparing community and hospital-based reports. PMID- 2903964 TI - The decline of offshore medical schools. PMID- 2903963 TI - Nasopharyngeal oxygen in children. AB - Hypoxia caused by pneumonia or bronchiolitis is a common cause of death in children in developing countries. Oxygen is very expensive in developing countries, and it is important that the limited supplies available be used as efficiently as possible. This study evaluated the administration of oxygen through an 8 FG catheter inserted into the nose to a depth equal to the distance from the side of the nose to the front of the ear, so that the tip of the catheter was just visible in the pharynx below the soft palate. A flow rate of 150 ml/kg/min gave an inspired oxygen concentration of about 50% in children less than 2 years old. Thus, newborn infants with pneumonia can usually be treated with 0.5 l/min and infants up to 12 months old with 1.0 l/min of nasopharyngeal oxygen. PMID- 2903965 TI - A plan for information in the National Health Service. PMID- 2903966 TI - Consensus conference: Progestagen use in postmenopausal women. PMID- 2903967 TI - "Eradication" of Campylobacter pylori: are we being misled? PMID- 2903968 TI - Paralysis of recurrent laryngeal nerve in Lyme disease. PMID- 2903969 TI - Camylofin intoxication reversed by naloxone. PMID- 2903971 TI - Non-invasive sampling method for detecting Chlamydia trachomatis. PMID- 2903970 TI - Gemfibrozil-induced headache. PMID- 2903972 TI - Viral gastroenteritis in foodhandlers. PMID- 2903973 TI - Cross-infection with Listeria monocytogenes confirmed by DNA fingerprinting. PMID- 2903974 TI - HIV in saliva. PMID- 2903975 TI - Transmission of HIV by blood from seronegative donors. PMID- 2903976 TI - Clearance and pump control of continuous arteriovenous haemodialysis. PMID- 2903977 TI - Effectiveness of condom use in preventing HIV infection in prostitutes. PMID- 2903978 TI - Gallbladder surgery in Scotland. PMID- 2903980 TI - Cytomegalovirus and IgA nephropathy. PMID- 2903979 TI - Rash due to nebulised pentamidine. PMID- 2903981 TI - Antiproteinuric effect of ACE inhibitors. PMID- 2903982 TI - Effect of allyloestrenol on deteriorating uteroplacental circulation. PMID- 2903983 TI - Blood velocity waveforms and placental vascular formation. PMID- 2903984 TI - Mitochondrial DNA deletion in encephalomyopathy. PMID- 2903985 TI - Embryopathy in infant conceived one year after termination of maternal etretinate: a reappraisal. PMID- 2903986 TI - Treatment of hyponatraemia secondary to water overload. PMID- 2903987 TI - Teratogenicity of isotretinoin. PMID- 2903988 TI - Thromboembolism and air travel. PMID- 2903989 TI - Danger of MAOI therapy after fluoxetine withdrawal. PMID- 2903990 TI - New genetic location of gentamicin-resistance in methicillin-resistant Staphylococcus aureus. PMID- 2903991 TI - Absent end-diastolic flow in first trimester umbilical artery. PMID- 2903992 TI - Does stressful venepuncture explain increased midnight serum cortisol concentration? PMID- 2903993 TI - Bismuth absorption from the colloidal subcitrate. PMID- 2903994 TI - Predictive value of EGF receptor in breast cancer. PMID- 2903995 TI - Thromboembolic events during combination chemotherapy for germ cell malignancy. PMID- 2903996 TI - Endoscopic sphincterotomy. PMID- 2903997 TI - Subcutaneous apomorphine for on-off oscillations in Parkinson's disease. PMID- 2903998 TI - Hypovitaminosis A, follicular ducts, and acne. PMID- 2903999 TI - Serum cholesterol response to dietary cholesterol and apoprotein E phenotype. PMID- 2904000 TI - Increased lipoprotein(a) levels in children with familial hypercholesterolaemia. PMID- 2904001 TI - Monocyte TNF production in gastrointestinal cancer. PMID- 2904002 TI - Alteplase (rtPA) patent case. PMID- 2904003 TI - Hantavirus disease in Sri Lanka. PMID- 2904004 TI - Alcohol and mortality in British men: explaining the U-shaped curve. AB - In a prospective study of 7735 middle-aged 7 British men, 504 of whom died in a follow-up period of 7.5 years, there was a U-shaped relationship between alcohol intake and total mortality and an inverse relationship with cardiovascular mortality, even after adjustment for age, cigarette smoking, and social class. These mortality patterns were seen in all smoking categories (with ex-smoking non drinkers having the highest mortality) and were observed in manual but not in non manual workers. The alcohol-mortality relationships (total and cardiovascular) were present only in men with cardiovascular or cardiovascular-related doctor diagnosed illnesses at initial examination. The data suggest that the observed alcohol-mortality relationships are produced by pre-existing disease and by the movement of men with such disease into non-drinking or occasional-drinking categories. The concept of a "protective" effect of drinking on mortality, ignoring the dynamic relationship between ill-health and drinking behaviour, is likely to be ill founded. PMID- 2904005 TI - Transmission of hepatitis B from hepatitis-B-seronegative subjects. AB - The polymerase chain reaction (PCR) was used to identify and characterise serum HBV DNA sequences in 3 patients negative for all HBV serological markers. HBsAg determinants were detected in 1 individual by monoclonal anti-HBsAg immunoradiometric assay. By use of sets of primers on the S and pre-S parts of the HBV genome the presence of HBV DNA was demonstrated in the serum of all 3 patients. Inoculation of human sera to 2 chimpanzees induced acute hepatitis in both animals; 1 became positive for HBsAg and anti-HBcAg and the other only for anti-HBsAg. Cloning of DNA sequences from viral isolates from 1 chimpanzee and 1 patient was accomplished after amplification of the 3' region of the S gene. Comparison of the partial nucleotide sequence with that of known HBV subtypes showed 0 and 1 point mutation, respectively, in the highly conserved 3' end of the S gene. Therefore the results show that PCR with HBV primers may unambigously identify HBV infectious particles among non-A, non-B viruses and is a potentially useful diagnostic test for detection of HBV DNA sequences in serum. PMID- 2904006 TI - Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double blind, placebo-controlled trial. AB - A double-blind, placebo-controlled study was carried out to see whether the synthetic E prostaglandin, misoprostol, would prevent gastric ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs). 420 patients with osteoarthritis and NSAID-associated abdominal pain were studied; they were receiving ibuprofen, piroxicam, or naproxen. Endoscopy was done at entry and after 1, 2, and 3 months of continuous treatment with 100 micrograms or 200 micrograms misoprostol or placebo, given four times daily with meals and at bedtime, concurrently with the NSAID. Abdominal pain was rated independently by patients and physicians. A treatment failure was defined as development of a gastric ulcer. Gastric ulcers (0.3 cm in diameter or greater) occurred less frequently (p less than 0.001) in both misoprostol treatment groups (5.6% 100 micrograms and 1.4% 200 micrograms) than in the placebo group (21.7%). The significant difference in ulcer formation between the placebo and the misoprostol treatment groups remained when comparisons were restricted to ulcers greater than 0.5 cm in diameter (12.3% placebo, 4.2% 100 micrograms misoprostol, and 0.7% 200 micrograms misoprostol). Mild to moderate, self-limiting diarrhoea was the most frequently reported adverse effect attributed to misoprostol. These results provide the first clear indication that NSAID-induced ulcers are preventable. PMID- 2904007 TI - Plasma dopamine beta-hydroxylase: rapid diagnostic test for recurrent hereditary polyserositis. AB - The diagnosis of recurrent hereditary polyserositis (RHP; also known as familial Mediterranean fever) remains one of exclusion since there has been no specific diagnostic laboratory test. A previous study suggested that the disorder is related to abnormal catecholamine metabolism. Plasma dopamine beta-hydroxylase (DBH) activity was assayed spectrophotometrically in 91 RHP patients and 162 controls. The activity was significantly higher in untreated symptom-free patients and in patients with acute attacks, than in controls (mean [SEM] 155.8 [14.1] vs 43.3 [1.9] mumol/min/1 p less than 0.0001). Colchicine treatment reduced DBH activity to control levels. The test showed a high diagnostic accuracy and specificity for RHP, whether the patient was symptom-free or having an acute attack. Moreover, it is easy to carry out. PMID- 2904009 TI - Measurement of exhaled chlorofluorocarbons. PMID- 2904008 TI - Differences in relative efficiency of nebulisers for pentamidine administration. AB - The study compared the pulmonary deposition of nebulised pentamidine when inhaled by way of different nebuliser systems by nine human-immunodeficiency-virus positive patients with a history of previous Pneumocystis carinii pneumonia. Pentamidine, 50 mg or 300 mg, mixed with technetium-99m-labelled human serum albumin in a total volume of 3 ml, was administered by way of three jet nebulisers (System 22', 'System 22 Mizer', and 'Respigard II') operated with a gas flow of 6 l/min, and one ultrasound nebuliser ('Pulmosonic'). Pulmonary and non-pulmonary isotope deposition was measured for each apparatus and adverse effects and lung function tests were recorded. For both doses of pentamidine, the system 22 mizer produced the largest pulmonary isotope deposition and it was completed in the shortest time. Oropharyngeal and gastric deposition were least with the respigard II, which also caused the fewest adverse effects. The adverse effects were greatest with the system 22 mizer and pulmosonic and the higher pentamidine dose, which also caused significant reductions in measurements of pulmonary function. It is concluded that either the system 22 mizer or the respigard II should be used to administer nebulised pentamidine. PMID- 2904010 TI - Persistent fetal circulation and extracorporeal membrane oxygenation. PMID- 2904011 TI - Management of patients with major injuries. PMID- 2904012 TI - Alcohol and mortality: the myth of the U-shaped curve. PMID- 2904013 TI - Misoprostol: ulcer prophylaxis at what cost? PMID- 2904014 TI - Imaging patients with suspected acoustic neuroma. PMID- 2904015 TI - Salmonella enteritidis phage type 4 infection: association with hen's eggs. AB - Epidemiological and microbiological investigation of the four outbreaks of Salmonella enteritidis phage type (PT) 4 that occurred in Wales in 1988 implicated foods containing shell eggs from hens as the vehicle of infection. In a case-control study of sporadic cases there was a significant association between infection and egg consumption in the 3 days before illness. These findings provide data to support the warnings from the Departments of Health in the United Kingdom about risks of infection from eating raw or undercooked hens' eggs. PMID- 2904017 TI - Post-neonatal mortality in the Third World. PMID- 2904016 TI - Effects of zidovudine in 365 consecutive patients with AIDS or AIDS-related complex. AB - Zidovudine (AZT) is of some benefit for selected patients with AIDS-related complex (ARC) or AIDS treated for up to 24 weeks. The activity and toxicity of oral AZT, 200 mg 4-hourly when possible, was evaluated in 365 consecutive patients with ARC (80) or AIDS (285) followed up for a mean of 31 weeks (range 2 52). A transient increase in body weight, Karnofsky index, and CD4 cell count was observed during the first months of therapy. However, by 6 months, these values had returned to their pretreatment levels and several opportunistic infections, malignancies, and deaths occurred. These disappointing results were partly related to the haematological toxicity of the drug, which led to interruption of treatment in many patients. Thus the benefits of AZT are limited to a few months for ARC and AIDS patients. At least for the most severely affected patients, reduced dosage of AZT may increase the therapeutic index. PMID- 2904019 TI - Acute treatment of severe haemorrhagic gastritis with high-dose sucralfate. PMID- 2904018 TI - Nutritional improvement without better health: Santa Maria Cauque, 15 years later. PMID- 2904020 TI - Fatal hydralazine-induced systemic lupus erythematosus. PMID- 2904021 TI - Beef to human insulin: dose for dose? PMID- 2904022 TI - Cholinergic side-effects of tetrahydroaminoacridine. PMID- 2904023 TI - Anal dilatation after duodenal trauma. PMID- 2904024 TI - Child abuse and maternal delusions. PMID- 2904025 TI - Are immunological markers of gluten-sensitive enteropathy detectable in IgA nephropathy? PMID- 2904027 TI - Leukaemia near Pilgrim nuclear power plant, Massachusetts. PMID- 2904026 TI - In-utero platelet transfusion for alloimmune thrombocytopenia. PMID- 2904028 TI - Is impaired visual development caused by perinatal hypoxia? PMID- 2904029 TI - Eosinophil count in healthy HTLV-I carriers. PMID- 2904030 TI - Failure of gentamicin when injected through 0.2 micron filter. PMID- 2904031 TI - Fluconazole resistance in Candida glabrata. PMID- 2904032 TI - Foscarnet infusion at home. PMID- 2904033 TI - Resection of haematogenous metastases. PMID- 2904034 TI - Response to criticism of the GMC. PMID- 2904036 TI - Life expectancy and planning care for the elderly. PMID- 2904035 TI - Surgical audit. PMID- 2904037 TI - Fatal breast cancer and concomitant causes of death. PMID- 2904038 TI - Endoscopic sphincterotomy in acute gallstone pancreatitis. PMID- 2904039 TI - Autoantibodies to topoisomerase I in primary biliary cirrhosis. PMID- 2904040 TI - Atypical hepatitis B virus in Spain? PMID- 2904041 TI - Classifying primary gut lymphomas. PMID- 2904042 TI - Thalidomide for chronic graft-versus-host disease in children. PMID- 2904043 TI - Alteplase versus placebo in myocardial infarction. PMID- 2904044 TI - Dietary calcium and hip fracture. PMID- 2904045 TI - Recumbent rest after embryo transfer. PMID- 2904046 TI - Prenatal diagnosis of cystic fibrosis. PMID- 2904047 TI - Screening for abdominal aortic aneurysm. PMID- 2904048 TI - Treating ascites. PMID- 2904049 TI - AIDS figures world wide. PMID- 2904050 TI - Evidence for an infective cause of childhood leukaemia: comparison of a Scottish new town with nuclear reprocessing sites in Britain. AB - Increases of leukaemia in young people that cannot be explained in terms of radiation have been recorded near both of Britain's nuclear reprocessing plants at Dounreay and Sellafield. These were built in unusually isolated places where herd immunity to a postulated widespread virus infection (to which leukaemia is a rare response) would tend to be lower than average. The large influxes of people in the 1950s to those areas might have been conducive to epidemics. The hypothesis has been tested in Scotland in an area identified at the outset as the only other rural area that received a large influx at the same time, when it was much more cut off from the nearest conurbation than at present--the New Town of Glenrothes. A significant increase of leukaemia below age 25 was found (10 observed, expected 3.6), with a greater excess below age 5 (7 observed, expected 1.5). PMID- 2904051 TI - New type of adhesive specificity revealed by oligosaccharide probes in Escherichia coli from patients with urinary tract infection. AB - A series of oligosaccharides derived from glycoproteins or from human milk were coupled to lipid and used as probes of the binding specificities of Escherichia coli isolated from patients with urinary tract infections. Selective binding to the glycoprotein oligosaccharide probes rich in mannose residues (high-mannose type) was demonstrated with fimbriated E coli that give mannose-inhibitable haemagglutination. This observation is in accordance with predictions from inhibition studies. Binding studies with the human milk oligosaccharide probes, which resemble structures found on host-cell membranes, revealed adhesive specificity unrelated to the presence of fimbriae. This new type of host oligosaccharide receptor is affected by the presence of the blood group genetic markers. It involves the disaccharide sequence linked to the membrane-associated lipid moiety of host-cell glycolipids, and may have a role in initiation of infection on damaged epithelial cell membranes. PMID- 2904052 TI - Oral contraceptive use and malignancies of the genital tract. Results from the Royal College of General Practitioners' Oral Contraception Study. AB - Of 47,000 women followed since 1968, those who had used oral contraceptives (ever users) had a significantly higher incidence rate of cervical cancer than never users. After standardisation of rates by age, parity, smoking, social class, number of previously normal cervical smears, and history of sexually transmitted disease, the excess was 41 per 100,000 woman-years for carcinoma-in-situ and 8 per 100,000 woman-years for invasive cervical cancer. Incidence increased with increasing duration of use: the standardised incidence rate for cervical cancer in women who had taken the pill for more than 10 years was four times than in never-users. Ever-users had a lower incidence of other uterine cancers (deficit 5 per 100,000 woman-years); a lower incidence of ovarian cancer was also found (deficit 4 per 100,000), but was not statistically significant. Overall, ever users had an excess incidence for genital tract cancers 37 per 100,000 woman years. This excess was mainly from carcinoma-in-situ of the cervix; the excess incidence of invasive cervical cancer was offset by the deficits in other uterine and ovarian cancers. Standardised mortality rates from genital cancer were similar in ever-users and never-users. Of relevance to clinical practice is the substantially different distribution of primary cancer sites: cervical cancer accounted for 75% of the invasive genital cancers and 74% of deaths from genital cancer in ever-users, but only 31% of the invasive cancers and 30% of deaths in never-users. PMID- 2904053 TI - Effects of simvastatin and cholestyramine on lipoprotein profile in hyperlipidaemia of nephrotic syndrome. AB - The efficacy, safety, and tolerability of simvastatin (20 mg twice a day) in the treatment of hyperlipidaemia due to unremitting nephrotic syndrome was compared with that of cholestyramine (8 g twice a day) in a crossover trial in ten patients. Two patients were taken off the protocol, one because he could not tolerate cholestyramine and one because of non-compliance with the cholestyramine regimen. No clinical or laboratory adverse experiences were noticed during the study in the other eight patients. Simvastatin was significantly more effective than cholestyramine in reducing the hyperlipidaemia--it produced a 36% decrease in total cholesterol and a 39% decrease in low density (LDL)-cholesterol, whereas cholestyramine reduced total cholesterol by 8% and LDL-cholesterol by 19%. With simvastatin the apolipoprotein B level decreased by 30%, whereas the apolipoprotein A level increased by 10%. PMID- 2904054 TI - Granulocyte-associated immunoglobulins in renal transplant recipients with cytomegalovirus infection. AB - Cytomegalovirus (CMV) infections in renal transplant recipients must be diagnosed rapidly, since they can be life-threatening unless chemotherapy is started early. Detection of granulocyte-associated immunoglobulins was compared with conventional virological methods for diagnosis of CMV infection in 71 renal transplant recipients. The granulocyte-associated immunoglobulin test (GAIT) was positive in 31 of 34 patients with proven CMV infections on the day of admission. By conventional virological criteria the diagnosis of active CMV infection could be made only 3-24 days later. The GAIT remained negative in 14 healthy transplant recipients, but it was positive in 9 of 23 patients with non-CMV-related post transplantation complications. The GAIT, which is not a virological method, could be useful for rapid diagnosis of CMV infection; its sensitivity was 0.91 and specificity 0.82 (for patients without detectable immunoglobulins on erythrocytes or platelets) and the processing time is only 3 h. PMID- 2904055 TI - Displacement of small bowel from pelvic radiation field. PMID- 2904056 TI - What makes microbes stick? PMID- 2904057 TI - Medical care of newborn babies. PMID- 2904058 TI - Two cheers for medical education, plus fads and froth. PMID- 2904059 TI - Recurrent staphylococcal skin infections. PMID- 2904061 TI - Do young patients with dyspepsia need investigation? AB - During 1986, 1386 patients with simple dyspepsia were referred by general practitioners for endoscopy (686) or double-contrast barium meal examination (700) at Leicester General Hospital. 618 (45%) were under the age of 45 years. Abnormal findings were more common in older than younger dyspeptic patients (58% vs 40% at endoscopy, 69% vs 25% by barium meal). Malignant disorders were diagnosed in 5% at endoscopy and 3% at barium meal, but in no patient under 45 years old. The incidence of malignant disorders at endoscopy was analysed for the 6 years 1980-86. Of 707 cases identified, only 13 (1.8%) occurred in patients under 45 years old; all 13 had symptoms suggesting pathology more serious than simple dyspepsia. It can be concluded that young patients with simple dyspepsia are overinvestigated. A majority can be treated safely with antacids and/or histamine receptor type 2 antagonists. PMID- 2904060 TI - Dobutamine stress test. PMID- 2904063 TI - Life expectancy in Down syndrome adults. AB - Life expectancy for adults with Down syndrome was calculated from data for 1610 liveborn affected individuals identified in over 1,500,000 consecutive live births in British Columbia from 1908 to 1981. Survival to 68 years of age, predicted from the available data, is better than in previous estimates, but is still much poorer than for the general population: about 44.4% and 13.6% of liveborn Down syndrome individuals will survive to 60 and 68 years, respectively, compared with 86.4% and 78.4% of the general population. PMID- 2904064 TI - Measles immunisation before the age of nine months? Position statement by the expanded programme on immunisation of the World Health Organisation. PMID- 2904062 TI - Degree of myopia in relation to intelligence and educational level. AB - Intelligence test scores and educational levels were compared for 5943 myopic and 9891 non-myopic 18-year-old men being drafted for military service in Denmark. The former were grouped by degree of myopia, in the range -0.25 diopters (D) to 7.75 D, according to the power of correcting lenses required. Myopes of all degrees had significantly higher test scores and educational levels than non myopes. However, the relation of these two variables to degree of myopia was not linear; for both variables there were no significant differences among myopia groups in the range -2.0 to -7.75 D. Whereas factors associated with intelligence and education seem to be important in triggering the onset of myopia, they seem to be much less important in determining the degree to which myopia progresses. PMID- 2904065 TI - Retrospective on a social critic.